Hereditary and acquired abnormalities in erythrocyte phosphofructokinase activity: the close association with altered 2,3-diphosphoglycerate levels.

PubMed

Tarui, S; Kono, N; Kuwajima, M; Kitani, T

1980-01-01

Specific deficiency of erythrocyte phosphofructokinase (PFK) activity in Type VII glycogenosis presents a good model for the analysis of the relationship between 2,3 diphosphoglycerate (2,3 DPG) level and glycolysis in erythrocytes since glycolytic flow is partially blocked at the regulatory step. Enzymatic analyses of glycolytic intermediates of erythrocytes from a patient with Type VII glycogenosis demonstrated that 2,3 DPG is markedly decreased in parallel with fructose-1,6-phosphate (FDP). In acidosis including diabetic ketoacidosis and uremic acidosis a fall in 2,3 DPG is also associated with a marked reduction in FDP. On the other hand, in respiratory alkalosis glycolytic intermediates shift to the opposite direction and forward crossover at PFK step appears, being associated with an elevation of 2,3 DPG. These data indicate a close relationship between 2,3 DPG level and PFK activity in erythrocytes. At least in acidosis and alkalosis the alteration in 2,3 DPG level may well be explained by changes in PFK activity caused mainly through allosteric mechanism. In addition, twelve cases with hereditary PFK deficiency in muscle and erythrocytes reported in the world are reviewed and discussed briefly.

Using Zero Balance Ultrafiltration with Dialysate as a Replacement Fluid for Hyperkalemia during Cardiopulmonary Bypass

PubMed Central

Heath, Michele; Raghunathan, Karthik; Welsby, Ian; Maxwell, Cory

2014-01-01

Abstract: Avoiding or managing hyperkalemia during cardiac surgery, especially in a patient with chronic renal insufficiency, can be challenging. Hyperkalemic cardioplegia solution is usually administered to achieve and maintain an electrical arrest of the heart. This solution eventually mixes in with the systemic circulation, contributing to elevated systemic potassium levels. Administration of packed red blood cells, hemolysis, tissue damage, and acidosis are also common causes of hyperkalemia. Current strategies to avoid or manage hyperkalemia include minimizing the volume of cardioplegia administered, shifting potassium from the extracellular into the intracellular space (by the administration of sodium bicarbonate when the pH is low and/or dextrose–insulin when effects relatively independent of serum pH are desired), using zero-balanced ultrafiltration (Z-BUF) with normal saline as the replacement fluid (to remove potassium from the body rather than simply shift the electrolyte across cellular membranes), and, occasionally, hemodialysis (1). We report the application of Z-BUF using an electrolyte-balanced, low potassium dialysate solution rather than isotonic saline to avoid a high chloride load and the potential for hyperchloremic acidosis to successfully treat hyperkalemia while on cardiopulmonary bypass. PMID:26357794

Refractory metabolic acidosis in patients with sepsis following hemiarthroplasty for femoral neck fracture: a causative role for paracetamol and flucloxacillin?

PubMed Central

Amer, Halima; Dockery, Frances; Barrett, Nicholas; George, Marc; Witek, Karolina; Stanton, Jeremy; Back, Diane

2011-01-01

The authors report two cases of pyroglutamic acidosis as a result of paracetamol and flucloxacillin therapy in patients with prosthesis infection following hemiarthroplasty for neck of femur fractures. Pyroglutamic acidosis is an important and often unrecognised cause of refractory metabolic acidosis that disproportionately affects older women, and can be caused by drugs such as paracetamol and flucloxacillin in the setting of sepsis, renal failure and malnutrition. Although relatively rare, the widespread use of these drugs in orthopaedic patients confirms the importance of this disorder. PMID:22689665

D-lactic acidosis in humans: systematic literature review.

PubMed

Bianchetti, Davide G A M; Amelio, Giacomo S; Lava, Sebastiano A G; Bianchetti, Mario G; Simonetti, Giacomo D; Agostoni, Carlo; Fossali, Emilio F; Milani, Gregorio P

2018-04-01

D-lactic acidosis is an uncommon and challenging form of metabolic acidosis that may develop in short bowel syndrome. It has been documented exclusively in case reports and small case series. We performed a review of the literature in the National Library of Medicine and Excerpta Medica databases. We identified 84 original reports published between 1977 and 2017. D-lactic acidosis was observed in 98 individuals ranging in age from 7 months to 86 years with short bowel syndrome. The clinical presentation included Kussmaul breathing, confusion, slurred speech, and gait disturbances. Furthermore, among 99 consecutive patients with short bowel syndrome, 21 reported having episodes with symptoms consistent with D-lactic acidosis. In addition, D-lactic acid might also contribute to acidosis in diabetes mellitus. Finally, abnormally high D-lactic acid was documented after administration or ingestion of large amounts of propylene glycol, as paraneoplastic phenomenon and perhaps also in a so far poorly characterized inherited inborn error of metabolism. In humans with short bowel syndrome (or carbohydrate malabsorption), D-lactic acidosis is likely rather common and under-recognized. This condition should be included in the differential diagnosis of unexplained high-gap metabolic acidosis where the anion causing the acidosis is not known. Furthermore, diabetic acidosis might be caused by accumulation of both ketone bodies and D-lactic acid. Finally, there are endogenous sources of D-lactic acid in subjects with propylene glycol intoxication.

D-Lactic acidosis in a boy with short bowel syndrome.

PubMed Central

Schoorel, E P; Giesberts, M A; Blom, W; van Gelderen, H H

1980-01-01

Metabolic acidosis in a 3-year-old child with short bowel syndrome led to the discovery of massive D-lactic aciduria. After normalisation of the intestinal bacterial flora, D-lactate disappeared together with the acidosis. Dysbacteriosis with excessive production of D-lactate by intestinal bacteria (unidentified) and subsequent absorption explains this unusual cause of metabolic acidosis. PMID:7436446

Acetaminophen-induced anion gap metabolic acidosis secondary to 5-oxoproline: a case report.

PubMed

Abkur, Tarig Mohammed; Mohammed, Waleed; Ali, Mohamed; Casserly, Liam

2014-12-06

5-oxoproline (pyroglutamic acid), an organic acid intermediate of the gamma-glutamyl cycle, is a rare cause of high anion gap metabolic acidosis. Acetaminophen and several other drugs have been implicated in the development of transient 5-oxoprolinemia in adults. We believe that reporting all cases of 5-oxoprolinemia will contribute to a better understanding of this disease. Here, we report the case of a patient who developed transient 5-oxoprolinemia following therapeutic acetaminophen use. A 75-year-old Caucasian woman was initially admitted for treatment of an infected hip prosthesis and subsequently developed transient high anion gap metabolic acidosis. Our patient received 40 g of acetaminophen over a 10-day period. After the more common causes of high anion gap metabolic acidosis were excluded, a urinary organic acid screen revealed a markedly increased level of 5-oxoproline. The acidosis resolved completely after discontinuation of the acetaminophen. 5-oxoproline acidosis is an uncommon cause of high anion gap metabolic acidosis; however, it is likely that it is under-diagnosed as awareness of the condition remains low and testing can only be performed at specialized laboratories. The diagnosis should be suspected in cases of anion gap metabolic acidosis, particularly in patients with recent acetaminophen use in combination with sepsis, malnutrition, liver disease, pregnancy or renal failure. This case has particular interest in medicine, especially for the specialties of nephrology and orthopedics. We hope that it will add more information to the literature about this rare condition.

Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis.

PubMed

Maiorana, Arianna; Vergine, Gianluca; Coletti, Valentina; Luciani, Matteo; Rizzo, Cristiano; Emma, Francesco; Dionisi-Vici, Carlo

2014-01-01

Refeeding syndrome can occur in several contexts of relative malnutrition in which an overaggressive nutritional support is started. The consequences are life threatening with multiorgan impairment, and severe electrolyte imbalances. During refeeding, glucose-involved insulin secretion causes abrupt reverse of lipolysis and a switch from catabolism to anabolism. This creates a sudden cellular demand for electrolytes (phosphate, potassium, and magnesium) necessary for synthesis of adenosine triphosphate, glucose transport, and other synthesis reactions, resulting in decreased serum levels. Laboratory findings and multiorgan impairment similar to refeeding syndrome also are observed in acute thiamine deficiency. The aim of this study was to determine whether thiamine deficiency was responsible for the electrolyte imbalance caused by tubular electrolyte losses. We describe two patients with leukemia who developed acute thiamine deficiency with an electrolyte pattern suggestive of refeeding syndrome, severe lactic acidosis, and evidence of proximal renal tubular dysfunction. A single thiamine administration led to rapid resolution of the tubular dysfunction and normalization of acidosis and electrolyte imbalance. This demonstrated that thiamine deficiency was responsible for the electrolyte imbalance, caused by tubular electrolyte losses. Our study indicates that, despite sharing many laboratory similarities, refeeding syndrome and acute thiamine deficiency should be viewed as separate entities in which the electrolyte abnormalities reported in cases of refeeding syndrome with thiamine deficiency and refractory lactic acidosis may be due to renal tubular losses instead of a shifting from extracellular to intracellular compartments. In oncologic and malnourished patients, individuals at particular risk for developing refeeding syndrome, in the presence of these biochemical abnormalities, acute thiamine deficiency should be suspected and treated because it promptly responds to thiamine administration. Copyright © 2014 Elsevier Inc. All rights reserved.

[Acetaminophen induced 5-oxoproline acidosis: An uncommon case of high anion gap metabolic acidosis].

PubMed

Lanot, A; Henri, P; Nowoczyn, M; Read, M H; Maucorps, C; Sassier, M; Lobbedez, T

2018-02-01

The most common causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis, and intoxications. Nevertheless, clinicians can be faced with unexplained HAGMA, with a need to look for less common etiologies. We describe a case of 5-oxoproline (pyroglutamate) acidosis due to chronic acetaminophen ingestion at therapeutic dose in a 79-year-old inpatient. The pathophysiology of this condition is detailed, with abnormalities in the gamma-glutamyl cycle due to acetaminophen ingestion and severe chronic morbidities, resulting in glutathione and cysteine deficiency and then accumulation of 5-oxoproline. In HAGMA, when usual causes have been excluded, 5-oxoproline acidosis should be suspected in patients with chronic morbidities and acetaminophen ingestion. This diagnosis should be kept in mind because it generally resolves quickly with cessation of acetaminophen and administration of intravenous fluids. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Mechanism of Hyperkalemia-Induced Metabolic Acidosis.

PubMed

Harris, Autumn N; Grimm, P Richard; Lee, Hyun-Wook; Delpire, Eric; Fang, Lijuan; Verlander, Jill W; Welling, Paul A; Weiner, I David

2018-05-01

Background Hyperkalemia in association with metabolic acidosis that are out of proportion to changes in glomerular filtration rate defines type 4 renal tubular acidosis (RTA), the most common RTA observed, but the molecular mechanisms underlying the associated metabolic acidosis are incompletely understood. We sought to determine whether hyperkalemia directly causes metabolic acidosis and, if so, the mechanisms through which this occurs. Methods We studied a genetic model of hyperkalemia that results from early distal convoluted tubule (DCT)-specific overexpression of constitutively active Ste20/SPS1-related proline-alanine-rich kinase (DCT-CA-SPAK). Results DCT-CA-SPAK mice developed hyperkalemia in association with metabolic acidosis and suppressed ammonia excretion; however, titratable acid excretion and urine pH were unchanged compared with those in wild-type mice. Abnormal ammonia excretion in DCT-CA-SPAK mice associated with decreased proximal tubule expression of the ammonia-generating enzymes phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase and overexpression of the ammonia-recycling enzyme glutamine synthetase. These mice also had decreased expression of the ammonia transporter family member Rhcg and decreased apical polarization of H + -ATPase in the inner stripe of the outer medullary collecting duct. Correcting the hyperkalemia by treatment with hydrochlorothiazide corrected the metabolic acidosis, increased ammonia excretion, and normalized ammoniagenic enzyme and Rhcg expression in DCT-CA-SPAK mice. In wild-type mice, induction of hyperkalemia by administration of the epithelial sodium channel blocker benzamil caused hyperkalemia and suppressed ammonia excretion. Conclusions Hyperkalemia decreases proximal tubule ammonia generation and collecting duct ammonia transport, leading to impaired ammonia excretion that causes metabolic acidosis. Copyright © 2018 by the American Society of Nephrology.

Acidosis in the hospital setting: is metformin a common precipitant?

PubMed

Scott, K A; Martin, J H; Inder, W J

2010-05-01

Acidosis is commonly seen in the acute hospital setting, and carries a high mortality. Metformin has been associated with lactic acidosis, but it is unclear how frequently this is a cause of acidosis in hospitalized inpatients. The aim of this study is to explore the underlying comorbidities and acute precipitants of acidosis in the hospital setting, including the relationship between type 2 diabetes (T2DM) and metformin use. Retrospective review. Cases of acidosis were identified using the hospital discharge code for acidosis for a 3-month period: October-December 2005. A total of 101 episodes of acidosis were identified: 29% had isolated respiratory acidosis, 31% had metabolic acidosis and 40% had a mixed respiratory and metabolic acidosis. There were 28 cases of confirmed lactic acidosis. Twenty-nine patients had T2DM, but only five of the subjects with T2DM had lactic acidosis; two were on metformin. The major risk factors for development of lactic acidosis were hepatic impairment (OR 33.8, P = 0.01), severe left ventricular dysfunction (OR 25.3, P = 0.074) and impaired renal function (OR 9.7, P = 0.09), but not metformin use. Most cases of metabolic and lactic acidosis in the hospital setting occur in patients not taking metformin. Hepatic, renal and cardiac dysfunction are more important predictors for the development of acidosis.

[Severe metabolic acidosis as a result of 5-oxoproline in acetaminophen use].

PubMed

Holman, Mirjam; ter Maaten, Jan C

2010-01-01

Acetaminophen overdose is a well known cause of liver function disorder and even hepatic failure. Less well known is that even a therapeutic dose of acetaminophen may lead to life-threatening problems. We describe an 84-year-old patient with severe metabolic acidosis and an increased anion gap secondary to 5-oxoproline elevation as a result of acetaminophen use. A systematic approach can help us to determine the cause of a high anion gap metabolic acidosis. In unexplained high anion gap acidosis clinicians should consider the possibility of 5-oxoproline accumulation in patients with risk factors such as acetaminophen use, female sex, malnutrition, infection, diminished liver function or renal failure.

Inhaled β-agonist therapy and respiratory muscle fatigue as under-recognised causes of lactic acidosis.

PubMed

Lau, Emily; Mazer, Jeffrey; Carino, Gerardo

2013-10-14

A 49-year-old man with chronic obstructive pulmonary disease (COPD) presented with significant tachypnoea, fevers, productive cough and increased work of breathing for the previous 4 days. Laboratory data showed elevated lactate of 3.2 mEq/L. Continuous inhaled ipratropium and albuterol nebuliser treatments were administered. Lactate levels increased to 5.5 and 3.9 mEq/L, at 6 and 12 h, respectively. No infectious source was found and the lactic acidosis cleared as the patient improved. The lactic acidosis was determined to be secondary to respiratory muscle fatigue and inhaled β-agonist therapy, two under-recognised causes of lactic acidosis in patients presenting with respiratory distress. Lactic acidosis is commonly used as a clinical marker for sepsis and shock, but in the absence of tissue hypoperfusion and severe hypoxia, alternative aetiologies for elevated levels should be sought to avoid unnecessary and potentially harmful medical interventions.

Choline Triggers Exacerbations of Chronic Obstructive Pulmonary Disease in Patients Infected with Pseudomonas aeruginosa.

PubMed

Grumelli, Sandra

2016-01-01

Although exacerbations of chronic obstructive pulmonary disease produced by Pseudomonas aeruginosa infections are a major cause of death, the molecular mechanism that produces them is not well known. Here we focused on the energetic basis of dyspnoea, hypercapnia and acidosis symptoms. We used an in vivo exacerbation model exposing mice to cigarette smoke and LPS, to mimic emphysema and infections, and choline challenges to trigger exacerbations, that showed 31% increased in the airway resistance for naïve mice and 250% for smoke/LPS treatment. Tissue resistance was increased 32%, in naïve mice, and 169% for smoke/LPS treatment. A decreased tissue elastance, was confirmed by decreased collagen content and increased alveoli chord length. Consequently, the O 2 demanded was 260% greater for smoke/LPS treated mice, to provide the energy required to pump the same volume of air then for naïve mice. The extra CO 2 produced per ml of air pumped caused hypercapnia and acidosis by 4% decrease in pH.In addition, the bacteria grown with choline had a decrease of 67% in phosphate, 23% ATP and 85% phospholipids with an increase of 57% in polyphosphates, 50% carbohydrates, 100% LPS, consuming 45% less energy relative to the bacteria grown with succinate. choline, released by P. aeruginosa , triggers exacerbation symptoms by increasing lung resistance, O 2 consumption and producing more pCO 2 in blood with dyspnea, hypercapnia and acidosis. The energetic shift of decreased O 2 bacterial demand and increased lung demand benefits the infection, thus restoring the energetic balance on the host will favor P. aeruginosa eradication.

5-oxoproline-induced anion gap metabolic acidosis after an acute acetaminophen overdose.

PubMed

Lawrence, David T; Bechtel, Laura K; Charlton, Nathan P; Holstege, Christopher P

2010-09-01

Metabolic acidosis after acute acetaminophen overdose is typically attributed to either transient lactic acidosis without evidence of hepatic injury or hepatic failure. High levels of the organic acid 5-oxoprolinuria are usually reported in patients with predisposing conditions, such as sepsis, who are treated in a subacute or chronic fashion with acetaminophen. The authors report a case of a 40-year-old woman who developed anion gap metabolic acidosis and somnolence after an acute acetaminophen overdose. Substantial hepatic damage did not occur, which ruled out acetaminophen-induced hepatic insufficiency as a cause of the patient's acidosis or altered mental status. Urinalysis revealed elevated levels of 5-oxoproline, suggesting that the patient's acute acetaminophen overdose was associated with marked anion gap metabolic acidosis due solely to 5-oxoproline without hepatic complications. The acidosis fully resolved with N-acetylcysteine treatment and supportive care including hydration.

The effect of CO2 and non-CO2-generating buffers on cerebral acidosis after cardiac arrest: A 31P NMR study.

PubMed

Rosenberg, J M; Martin, G B; Paradis, N A; Nowak, R M; Walton, D; Appleton, T J; Welch, K M

1989-04-01

There is controversy regarding the use of alkalinizing agents during reperfusion after cardiac arrest. The potential deleterious effects of sodium bicarbonate (bicarb) administration, including paradoxic cerebral acidosis, have led to the search for alternative agents. Tromethamine (tris) is a non-CO2-generating buffer that has been proposed for use during cardiopulmonary resuscitation. The purpose of this experiment was to compare the ability of tris with bicarb to correct brain pH (pH B) during reperfusion after a 12-minute cardiac arrest. Adult mongrel dogs were instrumented and placed in the bore of a Bruker Biospec 1.89 tesla superconducting magnet system. Ventricular fibrillation was induced; after 12 minutes, cardiopulmonary bypass was initiated and maintained for two hours with minimum flows of 80 mL/kg/min. Bicarb (n = 5) or tris (n = 5) were administered to correct arterial pH as rapidly as possible. 31P NMR spectra were obtained at baseline and throughout ischemia and reperfusion. The pH B was determined with the inorganic phosphate relative to the phosphocreatine resonance signal shift. Profile analysis indicates a difference between groups (P less than .02) related to an initial delay in pH B correction in the tris group. By 48 minutes of reperfusion, pH B did not differ between the groups. Moreover, there was no evidence of paradoxic cerebral acidosis in the bicarb group. Although tris corrects blood pH as quickly as bicarb, it is less effective in correcting pH B. Absence of paradoxic acidosis may be caused by efficient elimination of CO2 by cardiopulmonary bypass.

Recurrent high anion gap metabolic acidosis secondary to 5-oxoproline (pyroglutamic acid).

PubMed

Tailor, Prayus; Raman, Tuhina; Garganta, Cheryl L; Njalsson, Runa; Carlsson, Katarina; Ristoff, Ellinor; Carey, Hugh B

2005-07-01

High anion gap metabolic acidosis in adults is a severe metabolic disorder for which the primary organic acid usually is apparent by clinical history and standard laboratory testing. We report a case of recurrent high anion gap metabolic acidosis in a 48-year-old man who initially presented with anorexia and malaise. Physical examination was unrevealing. Arterial pH was 6.98, P co 2 was 5 mm Hg, and chemistry tests showed a bicarbonate level of 3 mEq/L (3 mmol/L), anion gap of 32 mEq/L (32 mmol/L), and a negative toxicology screen result, except for an acetaminophen (paracetamol) level of 7.5 mug/mL. Metabolic acidosis resolved with administration of intravenous fluids. Subsequently, he experienced 5 more episodes of high anion gap metabolic acidosis during an 8-month span. Methanol, ethylene glycol, acetone, ethanol, d -lactate, and hippuric acid screens were negative. Lactate levels were modestly elevated, and acetaminophen levels were elevated for 5 of 6 admissions. These episodes defied explanation until 3 urinary organic acid screens, obtained on separate admissions, showed striking elevations of 5-oxoproline levels. Inborn errors of metabolism in the gamma-glutamyl cycle causing recurrent 5-oxoprolinuria and high anion gap metabolic acidosis are rare, but well described in children. Recently, there have been several reports of apparent acquired 5-oxoprolinuria and high anion gap metabolic acidosis in adults in association with acetaminophen use. Acetaminophen may, in susceptible individuals, disrupt regulation of the gamma-glutamyl cycle and result in excessive 5-oxoproline production. Suspicion for 5-oxoproline-associated high anion gap metabolic acidosis should be entertained when the cause of high anion gap metabolic acidosis remains poorly defined, the anion gap cannot be explained reasonably by measured organic acids, and there is concomitant acetaminophen use.

Choline Triggers Exacerbations of Chronic Obstructive Pulmonary Disease in Patients Infected with Pseudomonas aeruginosa

PubMed Central

Grumelli, Sandra

2017-01-01

Background Although exacerbations of chronic obstructive pulmonary disease produced by Pseudomonas aeruginosa infections are a major cause of death, the molecular mechanism that produces them is not well known. Here we focused on the energetic basis of dyspnoea, hypercapnia and acidosis symptoms. Methods and Findings We used an in vivo exacerbation model exposing mice to cigarette smoke and LPS, to mimic emphysema and infections, and choline challenges to trigger exacerbations, that showed 31% increased in the airway resistance for naïve mice and 250% for smoke/LPS treatment. Tissue resistance was increased 32%, in naïve mice, and 169% for smoke/LPS treatment. A decreased tissue elastance, was confirmed by decreased collagen content and increased alveoli chord length. Consequently, the O2 demanded was 260% greater for smoke/LPS treated mice, to provide the energy required to pump the same volume of air then for naïve mice. The extra CO2 produced per ml of air pumped caused hypercapnia and acidosis by 4% decrease in pH. In addition, the bacteria grown with choline had a decrease of 67% in phosphate, 23% ATP and 85% phospholipids with an increase of 57% in polyphosphates, 50% carbohydrates, 100% LPS, consuming 45% less energy relative to the bacteria grown with succinate. Conclusion choline, released by P. aeruginosa, triggers exacerbation symptoms by increasing lung resistance, O2 consumption and producing more pCO2 in blood with dyspnea, hypercapnia and acidosis. The energetic shift of decreased O2 bacterial demand and increased lung demand benefits the infection, thus restoring the energetic balance on the host will favor P. aeruginosa eradication. PMID:29386986

Common, yet elusive: a case of severe anion gap acidosis.

PubMed

Agrawal, Akanksha; Kishlyansky, Marina; Biso, Sylvia; Patnaik, Soumya; Punjabi, Chitra

2017-09-01

Acid-base disturbances are common occurrence in hospitalized patients with life threatening complications. 5-oxoproline has been increasingly recognized as cause of high anion gap metabolic acidosis (AGMA) in association with chronic acetaminophen use. However, laboratory workup for it are not widely available. We report case of 56-year-old female with severe AGMA not attributable to ketoacidosis, lactic acidosis or toxic ingestion. History was significant for chronic acetaminophen use, and laboratory workup negative for all frequent causes of AGMA. Given history and clinical presentation, our suspicion for 5-oxoproline toxicity was high. Our patient required emergent hemodialysis and subsequently improved clinically. With an increasing awareness of the uncommon causes of high AGMA, tests should be more readily available to detect their presence. Physicians should be more vigilant of underdiagnosed causes of AGMA if the presentation and laboratory values do not reflect a common cause, as definitive treatment may vary based on the offending agent.

Dental Aspect of Distal Tubular Renal Acidosis with Genu Valgum Secondary to Rickets: A Case Report

PubMed Central

Bahadure, Rakesh N.; Thosar, Nilima; Kriplani, Ritika; Baliga, Sudhindra; Fulzele, Punit

2012-01-01

Distal renal tubular acidosis is a disease that occurs when the kidneys do not remove acid properly into the urine, leaving the blood too acidic (called acidosis). Distal renal tubular acidosis (type I RTA) is caused by a defect in the kidney tubes that causes acid to build up in the bloodstream. It ultimately results rickets which include chronic skeletal pain, in skeletal deformities, skeletal fractures. Rickets is among the most frequent childhood diseases in many developing countries. Dental problems in rickets include delayed eruption of permanent teeth, premature fall of deciduous teeth, defects in structure of teeth, enamel defects in permanent teeth (hypoplastic), pulp defects, intraglobular dentine, and caries tooth. Herewith, reported a case of distal tubular renal acidosis with genu valgum secondary to rickets, with pain and extraoral swelling associated with right and left mandibular 1st permanent molars. Teeth were infected with pulp without being involved with caries. Radiographically cracks in enamel and dentin were observed. Pulp revascularization with 46 and root canal treatment was done for 36 with followup of 1 year. PMID:22567455

Tumor Environmental Factors Glucose Deprivation and Lactic Acidosis Induce Mitotic Chromosomal Instability – An Implication in Aneuploid Human Tumors

PubMed Central

Zhu, Chunpeng; Hu, Xun

2013-01-01

Mitotic chromosomal instability (CIN) plays important roles in tumor progression, but what causes CIN is incompletely understood. In general, tumor CIN arises from abnormal mitosis, which is caused by either intrinsic or extrinsic factors. While intrinsic factors such as mitotic checkpoint genes have been intensively studied, the impact of tumor microenvironmental factors on tumor CIN is largely unknown. We investigate if glucose deprivation and lactic acidosis – two tumor microenvironmental factors – could induce cancer cell CIN. We show that glucose deprivation with lactic acidosis significantly increases CIN in 4T1, MCF-7 and HCT116 scored by micronuclei, or aneuploidy, or abnormal mitosis, potentially via damaging DNA, up-regulating mitotic checkpoint genes, and/or amplifying centrosome. Of note, the feature of CIN induced by glucose deprivation with lactic acidosis is similar to that of aneuploid human tumors. We conclude that tumor environmental factors glucose deprivation and lactic acidosis can induce tumor CIN and propose that they are potentially responsible for human tumor aneuploidy. PMID:23675453

Draft Genome Sequence of Lactobacillus delbrueckii Strain #22 Isolated from a Patient with Short Bowel Syndrome and Previous d-Lactic Acidosis and Encephalopathy

PubMed Central

Fischer, Florence; Glowatzki, Fabian; Fritzenwanker, Moritz; Hain, Torsten; Zechel-Gran, Silke; Giffhorn-Katz, Susanne; Neubauer, Bernd A.

2016-01-01

d-Lactic acidosis with associated encephalopathy caused by overgrowth of intestinal lactic acid bacteria is a rarely diagnosed neurological complication of patients with short bowel syndrome. Here, we report the draft genome sequence of Lactobacillus delbrueckii strain #22 isolated from a patient with short bowel syndrome and previous d-lactic acidosis/encephalopathy. PMID:27469967

Severe anion gap metabolic acidosis from acetaminophen use secondary to 5-oxoproline (pyroglutamic acid) accumulation.

PubMed

Zand, Ladan; Muriithi, Angela; Nelsen, Eric; Franco, Pablo M; Greene, Eddie L; Qian, Qi; El-Zoghby, Ziad M

2012-12-01

Anion gap metabolic acidosis (AGMA) is commonly encountered in medical practice. Acetaminophen-induced AGMA is, however, not widely recognized. We report 2 cases of high anion gap metabolic acidosis secondary to 5-oxoproline accumulation resulting from acetaminophen consumption: the first case caused by acute one-time ingestion of large quantities of acetaminophen and the second case caused by chronic repeated ingestion in a patient with chronic liver disease. Recognition of this entity facilitated timely diagnosis and effective treatment. Given acetaminophen is commonly used over the counter medication, increased recognition of this adverse effect is of important clinical significance.

A not so simple analgesic

PubMed Central

Howie, Sarah; Tarn, Anne; Soper, Charles

2010-01-01

Many of the common causes of a high anion gap metabolic acidosis, like salicylate toxicity or diabetic ketoacidosis, are well recognized and promptly treated. Pyroglutamic acidosis (or 5-oxoproline acidosis) is a less common cause and is likely substantially underdiagnosed for two reasons: firstly, urine or serum measurements of pyroglutamic acid are performed only in specialist laboratories, and secondly, because awareness of the condition is still low, despite widespread reports in the medical and biochemical literature. The condition is often precipitated by the chronic use of paracetamol. Paracetamol is increasingly being widely prescribed as an alternative to NSAIDs often in maximal doses, given its innocuous reputation, and we anticipate more similar presentations. We present a case of a young pregnant woman who developed a severe metabolic acidosis secondary to raised pyroglutamate. Her treatment necessitated an emergency Caesarean section, ventilation and haemodiafiltration, despite normal renal function. We provide a reminder of other risk factors associated with the diagnosis. PMID:25949471

Acetaminophen-induced anion gap metabolic acidosis and 5-oxoprolinuria (pyroglutamic aciduria) acquired in hospital.

PubMed

Humphreys, Benjamin D; Forman, John P; Zandi-Nejad, Kambiz; Bazari, Hasan; Seifter, Julian; Magee, Colm C

2005-07-01

A rare cause of high anion gap acidosis is 5-oxoproline (pyroglutamic acid), an organic acid intermediate of the gamma-glutamyl cycle. Acetaminophen and several other drugs have been implicated in the development of transient 5-oxoprolinemia in adults. We report the case of a patient with lymphoma who was admitted for salvage chemotherapy. The patient subsequently developed fever and neutropenia and was administered 20.8 g of acetaminophen during 10 days. During this time, anion gap increased from 14 to 30 mEq/L (14 to 30 mmol/L) and altered mental status developed. After usual causes of high anion gap acidosis were ruled out, a screen for urine organic acids showed 5-oxoproline levels elevated at 58-fold greater than normal values. Predisposing factors in this case included renal dysfunction and sepsis. Clinicians need to be aware of this unusual cause of anion gap acidosis because it may be more common than expected, early discontinuation of the offending agent is therapeutic, and administration of N -acetylcysteine could be beneficial.

Metformin-Induced Lactic Acidosis (MILA): Review of current diagnostic paradigm.

PubMed

Krowl, Lauren; Al-Khalisy, Hassan; Kaul, Pratibha

2018-05-01

A new diagnostic paradigm has been proposed to better categorize causes of Metformin-Associated Lactic Acidosis (MALA). The diagnostic criteria defines a link between Metformin and lactic acidosis if lactate is >5mmol/L, Ph<7.35 and Metformin assay >5mg/L. Metformin assays are not readily available in emergency departments including nationwide Veteran's Affairs Hospitals; thereby making this proposed classification tool difficult to use in today's clinical practice. We describe a case report of a 45-year-old male, who took twice the amount of Metformin prescribed and presented with Metformin-induced lactic acidosis. According to the new criterion, our case would be classified as "Lactic Acidosis in Metformin-Treated Patients (LAMT)." However, the term LAMT does not distinguish between a septic patient taking Metformin with lactic acidosis, and a patient who ingested toxic amounts of Metformin and has lactic acidosis (in absence of Metformin assay). Our case highlights the importance of medication reconciliation done on arrival to emergency department. Timing and dosing of Metformin in patients who present to the emergency department with lactic acidosis may cinch the diagnosis of Metformin-Induced Lactic Acidosis (MILA) in the absence of a Metformin assay but in the right clinical context. Copyright © 2018 Elsevier Inc. All rights reserved.

Draft Genome Sequence of Lactobacillus delbrueckii Strain #22 Isolated from a Patient with Short Bowel Syndrome and Previous d-Lactic Acidosis and Encephalopathy.

PubMed

Domann, Eugen; Fischer, Florence; Glowatzki, Fabian; Fritzenwanker, Moritz; Hain, Torsten; Zechel-Gran, Silke; Giffhorn-Katz, Susanne; Neubauer, Bernd A

2016-07-28

d-Lactic acidosis with associated encephalopathy caused by overgrowth of intestinal lactic acid bacteria is a rarely diagnosed neurological complication of patients with short bowel syndrome. Here, we report the draft genome sequence of Lactobacillus delbrueckii strain #22 isolated from a patient with short bowel syndrome and previous d-lactic acidosis/encephalopathy. Copyright © 2016 Domann et al.

Acidosis and Urinary Calcium Excretion: Insights from Genetic Disorders

PubMed Central

Cordat, Emmanuelle; Chambrey, Régine; Dimke, Henrik; Eladari, Dominique

2016-01-01

Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis. PMID:27468975

Differential Diagnosis of Nongap Metabolic Acidosis: Value of a Systematic Approach

PubMed Central

Madias, Nicolaos E.

2012-01-01

Summary Nongap metabolic acidosis is a common form of both acute and chronic metabolic acidosis. Because derangements in renal acid-base regulation are a common cause of nongap metabolic acidosis, studies to evaluate renal acidification often serve as the mainstay of differential diagnosis. However, in many cases, information obtained from the history and physical examination, evaluation of the electrolyte pattern (to determine if a nongap acidosis alone or a combined nongap and high anion gap metabolic acidosis is present), and examination of the serum potassium concentration (to characterize the disorder as hyperkalemic or hypokalemic in nature) is sufficient to make a presumptive diagnosis without more sophisticated studies. If this information proves insufficient, indirect estimates or direct measurement of urinary NH4+ concentration, measurement of urine pH, and assessment of urinary HCO3− excretion can help in establishing the diagnosis. This review summarizes current information concerning the pathophysiology of this electrolyte pattern and the value and limitations of all of the diagnostic studies available. It also provides a systematic and cost-effective approach to the differential diagnosis of nongap metabolic acidosis. PMID:22403272

Increased anion gap metabolic acidosis as a result of 5-oxoproline (pyroglutamic acid): a role for acetaminophen.

PubMed

Fenves, Andrew Z; Kirkpatrick, Haskell M; Patel, Viralkumar V; Sweetman, Lawrence; Emmett, Michael

2006-05-01

The endogenous organic acid metabolic acidoses that occur commonly in adults include lactic acidosis; ketoacidosis; acidosis that results from the ingestion of toxic substances such as methanol, ethylene glycol, or paraldehyde; and a component of the acidosis of kidney failure. Another rare but underdiagnosed cause of severe, high anion gap metabolic acidosis in adults is that due to accumulation of 5-oxoproline (pyroglutamic acid). Reported are four patients with this syndrome, and reviewed are 18 adult patients who were reported previously in the literature. Twenty-one patients had major exposure to acetaminophen (one only acute exposure). Eighteen (82%) of the 22 patients were women. Most of the patients were malnourished as a result of multiple medical comorbidities, and most had some degree of kidney dysfunction or overt failure. The chronic ingestion of acetaminophen, especially by malnourished women, may generate high anion gap metabolic acidosis. This undoubtedly is an underdiagnosed condition because measurements of serum and/or urinary 5-oxoproline levels are not readily available.

Modulation of ventricular transient outward K+ current by acidosis and its effects on excitation-contraction coupling

PubMed Central

Saegusa, Noriko; Garg, Vivek

2013-01-01

The contribution of transient outward current (Ito) to changes in ventricular action potential (AP) repolarization induced by acidosis is unresolved, as is the indirect effect of these changes on calcium handling. To address this issue we measured intracellular pH (pHi), Ito, L-type calcium current (ICa,L), and calcium transients (CaTs) in rabbit ventricular myocytes. Intracellular acidosis [pHi 6.75 with extracellular pH (pHo) 7.4] reduced Ito by ∼50% in myocytes with both high (epicardial) and low (papillary muscle) Ito densities, with little effect on steady-state inactivation and activation. Of the two candidate α-subunits underlying Ito, human (h)Kv4.3 and hKv1.4, only hKv4.3 current was reduced by intracellular acidosis. Extracellular acidosis (pHo 6.5) shifted Ito inactivation toward less negative potentials but had negligible effect on peak current at +60 mV when initiated from −80 mV. The effects of low pHi-induced inhibition of Ito on AP repolarization were much greater in epicardial than papillary muscle myocytes and included slowing of phase 1, attenuation of the notch, and elevation of the plateau. Low pHi increased AP duration in both cell types, with the greatest lengthening occurring in epicardial myocytes. The changes in epicardial AP repolarization induced by intracellular acidosis reduced peak ICa,L, increased net calcium influx via ICa,L, and increased CaT amplitude. In summary, in contrast to low pHo, intracellular acidosis has a marked inhibitory effect on ventricular Ito, perhaps mediated by Kv4.3. By altering the trajectory of the AP repolarization, low pHi has a significant indirect effect on calcium handling, especially evident in epicardial cells. PMID:23585132

D-lactic acidosis - case report and review of the literature.

PubMed

Fabian, Elisabeth; Kramer, Ludwig; Siebert, Franz; Högenauer, Christoph; Raggam, Reinhard Bernd; Wenzl, Heimo; Krejs, Guenter J

2017-01-01

D-lactic acidosis is a rare complication that occurs mainly in patients with malabsorption due to a surgically altered gastrointestinal tract anatomy, namely in short bowel syndrome or after bariatric surgery. It is characterized by rapid development of neurological symptoms and severe metabolic acidosis, often with a high serum anion gap. Malabsorbed carbohydrates can be fermented by colonic microbiota capable of producing D-lactic acid. Routine clinical assessment of serum lactate covers only L-lactic acid; when clinical suspicion for D-lactic acidosis is high, special assays for D-lactic acid are called for. A serum level of more than 3 mmol/L of D-lactate confirms the diagnosis. Management includes correction of metabolic acidosis by intravenous bicarbonate, restriction of carbohydrates or fasting, and antibiotics to eliminate intestinal bacteria that produce D-lactic acid. We report a case of D-lactic acidosis in a patient with short bowel syndrome and review the pathophysiology of D-lactic acidosis with its biochemical and clinical features. D-lactic acidosis should be considered when patients with short bowel syndrome or other malabsorption syndromes due to an altered gastrointestinal tract anatomy present with metabolic acidosis and neurological symptoms that cannot be attributed to other causes. With the growing popularity of bariatric surgery, this metabolic derangement may be seen more frequently in the future. © Georg Thieme Verlag KG Stuttgart · New York.

[Pyroglutamic acidemia associated with acetaminophen].

PubMed

Alados Arboledas, F J; de la Oliva Senovilla, P; García Muñoz, Ma J; Alonso Melgar, A; Ruza Tarrío, F

2007-12-01

We report a case of pyroglutamic acidemia probably related to acetaminophen administration. A 16-month boy recovering from hemolytic uremic syndrome abruptly developed unexplained high anion gap metabolic acidosis requiring hemodialysis. Septic shock, lactic acidosis and salicylate intoxication were ruled out. Betahydroxybutyrate and acetoacetate levels were within the normal range. No osmolarity gap or high amino acid levels were found. Urine and blood pyroglutamic acid levels were 392 mmol/mol creatinine (reference range: 9-55) and 9.8 mmol/L (reference range<0.16), respectively. The patient was receiving acetaminophen. We conclude that pyroglutamic acidosis should be considered in patients receiving acetaminophen who abruptly develop high anion gap metabolic acidosis not attributable to more common causes.

An unusual cause of high anion gap metabolic acidosis: pyroglutamic acidemia. A case report.

PubMed

Romero, Jorge E; Htyte, Nay

2013-01-01

Pyroglutamic acidemia is an uncommon metabolic disorder, which is usually diagnosed at early ages. The mechanism of action is thought to be glutathione depletion, and its clinical manifestations consist of hemolytic anemia, mental retardation, ataxia, and chronic metabolic acidosis. However, an acquired form has been described in adult patients, who usually present with confusion, respiratory distress, and high anion gap metabolic acidosis (HAGMA). It is also associated with many conditions, including chronic acetaminophen consumption. A 68-year-old white male, with chronic acetaminophen use presented to our service on multiple occasions with severe HAGMA. The patient was admitted to the intensive care unit and required mechanical ventilation and aggressive supportive measures. After ruling out the most frequent etiologies for his acid-base disorder and considering the long history of Tylenol ingestion, his 5-oxiproline (pyroglutamic acid) levels were sent to diagnose pyroglutamic acidemia. Clinicians need to be aware of this cause for metabolic acidosis since it might be a more common metabolic disturbance in compromised patients than would be expected. Subjects with HAGMA that cannot be explained by common causes should be tested for the presence of 5-oxoproline. Discontinuation of the offending drug is therapeutic.

D-lactic acidosis: an unusual cause of encephalopathy in a patient with short bowel syndrome.

PubMed

Dahlqvist, G; Guillen-Anaya, M A; Vincent, M F; Thissen, J P; Hainaut, P

2013-01-01

A 24-year-old woman with a short bowel syndrome following post-ischemic small bowel resection, developed several episodes of lethargy, echolalia and ataxia. D-lactic acidosis was identified as the cause of neurological disturbances. This infrequent disorder can be precipitated by intake of a large amount of sugars, in patients with short bowel syndrome. It should be suspected in the presence of metabolic acidosis with increased anion gap and a normal level of L-lactic acid. The diagnosis relies on the specific dosage of D-lactic stereoisomer. Proper management involves rehydration, diet adaptation and oral administration of poorly absorbed antibiotics in order to modify the colonic flora responsible for D-lactic production.

[Starvation ketosis in a breastfeeding woman].

PubMed

Monnier, D; Goulenok, T; Allary, J; Zarrouk, V; Fantin, B

2015-12-01

Bovine ketosis is a rare cause of metabolic acidosis. It is a starvation ketosis that appears in lactating woman. A 29-year-old woman had a previous gastric surgery one month ago while breastfeeding her 6-month child. She presented to emergency with dyspnea, fatigue, weight loss and anorexia. The explorations revealed a serious metabolic acidosis with a high anion gap, for which all other causes have been eliminated. A restrictive diet in lactating patients is a major risk of ketosis or bovine ketosis. Medico-surgical treatment of obesity during lactation seems unreasonable. Breastfeeding should be systematically sought before a medical and surgical management of obesity. With the spread of bariatric surgery, starvation ketosis is a cause of metabolic acidosis not to ignore. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Autophagic clearance of mitochondria in the kidney copes with metabolic acidosis.

PubMed

Namba, Tomoko; Takabatake, Yoshitsugu; Kimura, Tomonori; Takahashi, Atsushi; Yamamoto, Takeshi; Matsuda, Jun; Kitamura, Harumi; Niimura, Fumio; Matsusaka, Taiji; Iwatani, Hirotsugu; Matsui, Isao; Kaimori, Junya; Kioka, Hidetaka; Isaka, Yoshitaka; Rakugi, Hiromi

2014-10-01

Metabolic acidosis, a common complication of CKD, causes mitochondrial stress by undefined mechanisms. Selective autophagy of impaired mitochondria, called mitophagy, contributes toward maintaining cellular homeostasis in various settings. We hypothesized that mitophagy is involved in proximal tubular cell adaptations to chronic metabolic acidosis. In transgenic mice expressing green fluorescent protein-tagged microtubule-associated protein 1 light chain 3 (GFP-LC3), NH4Cl loading increased the number of GFP puncta exclusively in the proximal tubule. In vitro, culture in acidic medium produced similar results in proximal tubular cell lines stably expressing GFP-LC3 and facilitated the degradation of SQSTM1/p62 in wild-type cells, indicating enhanced autophagic flux. Upon acid loading, proximal tubule-specific autophagy-deficient (Atg5-deficient) mice displayed significantly reduced ammonium production and severe metabolic acidosis compared with wild-type mice. In vitro and in vivo, acid loading caused Atg5-deficient proximal tubular cells to exhibit reduced mitochondrial respiratory chain activity, reduced mitochondrial membrane potential, and fragmented morphology with marked swelling in mitochondria. GFP-LC3-tagged autophagosomes colocalized with ubiquitinated mitochondria in proximal tubular cells cultured in acidic medium, suggesting that metabolic acidosis induces mitophagy. Furthermore, restoration of Atg5-intact nuclei in Atg5-deficient proximal tubular cells increased mitochondrial membrane potential and ammoniagenesis. In conclusion, metabolic acidosis induces autophagy in proximal tubular cells, which is indispensable for maintaining proper mitochondrial functions including ammoniagenesis, and thus for adapted urinary acid excretion. Our results provide a rationale for the beneficial effect of alkali supplementation in CKD, a condition in which autophagy may be reduced, and suggest a new therapeutic option for acidosis by modulating autophagy. Copyright © 2014 by the American Society of Nephrology.

Profound metabolic acidosis and oxoprolinuria in an adult.

PubMed

Hodgman, Michael J; Horn, James F; Stork, Christine M; Marraffa, Jeanna M; Holland, Michael G; Cantor, Richard; Carmel, Patti M

2007-09-01

Profound metabolic acidosis in critically ill adults sometimes remains unexplained despite extensive evaluation. A 58-year-old female presented in a confused state to the emergency department; she had been confused for several days. Laboratory evaluation revealed a high anion gap metabolic acidosis and modestly elevated acetaminophen level. Lactic acid was only modestly elevated. There was no evidence of ketoacids, salicylate, methanol, or ethylene glycol. A urine sample submitted on day 1 of hospitalization revealed a markedly elevated level of 5-oxoproline. Originally described in children with an inherited defect of glutathione synthetase, 5-oxoproline is an unusual cause of metabolic acidosis. More recently this disturbance has been recognized in critically ill adults without a recognized inherited metabolic disorder. In most of these cases there has been the concomitant use of acetaminophen. Any causal relationship between acetaminophen and this disturbance is speculative. In critically ill adults with unexplained metabolic acidosis, 5-Oxoproline should be considered in the differential.

Metabolic acidosis in an infant associated with permethrin toxicity.

PubMed

Goksugur, Sevil B; Karatas, Zehra; Goksugur, Nadir; Bekdas, Mervan; Demircioglu, Fatih

2015-01-01

Pyrethroids are broad-spectrum insecticides. Permethrin intoxication due to topical application has not been documented in humans. We report a 20-month-old infant who had used 5% permethrin lotion topically for scabies treatment. Approximately 60 mL (20 mL/day) was used and after the third application he developed agitation, nausea, vomiting, respiratory distress, tachycardia, and metabolic acidosis. His clinical symptoms and metabolic acidosis normalized within 20 hours. His follow-up was unremarkable. Toxicity of permethrin is rare, and although permethrin is a widely and safely used topical agent in the treatment of scabies and lice, inappropriate use may rarely cause toxicity. Moreover, in cases of unexplained metabolic acidosis, topically applied medications should be carefully investigated. © 2014 Wiley Periodicals, Inc.

Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis.

PubMed

Kraut, Jeffrey A; Xing, Shelly Xiaolei

2011-09-01

An increase in serum osmolality and serum osmolal gap with or without high-anion-gap metabolic acidosis is an important clue to exposure to one of the toxic alcohols, which include methanol, ethylene glycol, diethylene glycol, propylene glycol, or isopropanol. However, the increase in serum osmolal gap and metabolic acidosis can occur either together or alone depending on several factors, including baseline serum osmolal gap, molecular weight of the alcohol, and stage of metabolism of the alcohol. In addition, other disorders, including diabetic or alcoholic ketoacidosis, acute kidney injury, chronic kidney disease, and lactic acidosis, can cause high-anion-gap metabolic acidosis associated with an increased serum osmolal gap and therefore should be explored in the differential diagnosis. It is essential for clinicians to understand the value and limitations of osmolal gap to assist in reaching the correct diagnosis and initiating appropriate treatment. In this teaching case, we present a systematic approach to diagnosing high serum osmolality and increased serum osmolal gap with or without high-anion-gap metabolic acidosis. Published by Elsevier Inc.

D-lactic acidosis in neonatal ruminants.

PubMed

Lorenz, Ingrid; Gentile, Arcangelo

2014-07-01

Metabolic acidosis in calves with neonatal diarrhea was believed to be mainly caused by the loss of bicarbonate via the intestines or the formation of L-lactate during anaerobic glycolysis after tissue hypoperfusion in dehydrated calves. Because D-lactate was not considered to be of interest in human or veterinary medicine, routine diagnostic methods targeted the detection of L-lactate only. The development of stereospecific assays for the measurement of D-lactate facilitated research. This article summarizes the available information on D-lactic metabolic acidosis in neonatal ruminants. Copyright © 2014 Elsevier Inc. All rights reserved.

Linezolid-induced lactic acidosis: the thin line between bacterial and mitochondrial ribosomes.

PubMed

Santini, Alessandro; Ronchi, Dario; Garbellini, Manuela; Piga, Daniela; Protti, Alessandro

2017-07-01

Linezolid inhibits bacterial growth by targeting bacterial ribosomes and by interfering with bacterial protein synthesis. Lactic acidosis is a rare, but potentially lethal, side effect of linezolid. Areas covered: The pathogenesis of linezolid-induced lactic acidosis is reviewed with special emphasis on aspects relevant to the recognition, prevention and treatment of the syndrome. Expert opinion: Linezolid-induced lactic acidosis reflects the untoward interaction between the drug and mitochondrial ribosomes. The inhibition of mitochondrial protein synthesis diminishes the respiratory chain enzyme content and thus limits aerobic energy production. As a result, anaerobic glycolysis and lactate generation accelerate independently from tissue hypoxia. In the absence of any confirmatory test, linezolid-induced lactic acidosis should be suspected only after exclusion of other, more common, causes of lactic acidosis such as hypoxemia, anemia or low cardiac output. Normal-to-high whole-body oxygen delivery, high venous oxygen saturation and lack of response to interventions that effectively increase tissue oxygen provision all suggest a primary defect in oxygen use at the mitochondrial level. During prolonged therapy with linezolid, blood drug and lactate levels should be regularly monitored. The current standard-of-care treatment of linezolid-induced lactic acidosis consists of drug withdrawal to reverse mitochondrial intoxication and intercurrent life support.

Metabolic Acidosis or Respiratory Alkalosis? Evaluation of a Low Plasma Bicarbonate Using the Urine Anion Gap.

PubMed

Batlle, Daniel; Chin-Theodorou, Jamie; Tucker, Bryan M

2017-09-01

Hypobicarbonatemia, or a reduced bicarbonate concentration in plasma, is a finding seen in 3 acid-base disorders: metabolic acidosis, chronic respiratory alkalosis and mixed metabolic acidosis and chronic respiratory alkalosis. Hypobicarbonatemia due to chronic respiratory alkalosis is often misdiagnosed as a metabolic acidosis and mistreated with the administration of alkali therapy. Proper diagnosis of the cause of hypobicarbonatemia requires integration of the laboratory values, arterial blood gas, and clinical history. The information derived from the urinary response to the prevailing acid-base disorder is useful to arrive at the correct diagnosis. We discuss the use of urine anion gap, as a surrogate marker of urine ammonium excretion, in the evaluation of a patient with low plasma bicarbonate concentration to differentiate between metabolic acidosis and chronic respiratory alkalosis. The interpretation and limitations of urine acid-base indexes at bedside (urine pH, urine bicarbonate, and urine anion gap) to evaluate urine acidification are discussed. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The effect of lactic acidosis on the generation and compensation of mixed respiratory-metabolic acidosis in neonatal calves.

PubMed

Bleul, U; Götz, E

2013-05-18

Postnatal mixed respiratory-metabolic acidosis is common in calves, and depending on its severity can impair vitality or even cause death. Carbon dioxide accounts for the respiratory component and L-lactate for the metabolic component of the mixed acidosis, but it remains unclear which component determines the severity and duration of the acidosis. In a first attempt to clarify, this was investigated retrospectively in 31 calves during the first two hours of life, and in 13 calves during the first three days of life. Venous blood was collected for blood gas analysis and measurement of acid-base variables and L-lactate concentration. pH Was more strongly correlated with L-lactate concentration (r(2)=0.808) than with partial pressure of CO2 (pCO2, r(2)=0.418). Duration of parturition had a distinct effect on pH and L-lactate concentration but not on pCO2; calves born within six hours of rupture of the allantoic sac had a higher pH and lower L-lactate concentration than calves born after a longer duration of parturition (both P<0.01). Normalisation of pCO2 took four hours and normalisation of L-lactate took 48 hours. It was concluded that L-lactate is a more important factor in the pathogenesis of acidosis than pCO2, and that the duration of metabolic acidosis exceeds that of respiratory acidosis in perinatal asphyxia of calves.

A Case of Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome with Intracardiac Thrombus [corrected].

PubMed

Joo, Jung-Chul; Seol, Myung Do; Yoon, Jin Won; Lee, Young Soo; Kim, Dong-Keun; Choi, Yong Hoon; Ahn, Hyo Seong; Cho, Wook Hyun

2013-03-01

Myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a multisystem clinical syndrome manifested by mitochondrial myopathy, encephalopathy, lactic acidosis and recurrent stroke-like episodes. A 27-year-old female with MELAS syndrome presented with cerebral infarction. Echocardiography revealed a thrombus attached to the apex of the hypertrophied left ventricle, with decreased systolic function. The embolism of the intracardiac thrombus might have been the cause of stroke. There should be more consideration given to the increased possibility of intracardiac thrombus formation when a MELAS patient with cardiac involvement is encountered.

Acquired 5-oxoproline acidemia successfully treated with N-acetylcysteine.

PubMed

Hundemer, Gregory L; Fenves, Andrew Z

2017-04-01

Acquired 5-oxoprolinemia is increasingly recognized as a cause of anion gap metabolic acidosis. It predominantly occurs in chronically ill, malnourished women with impaired renal function and chronic acetaminophen ingestion. Depletion of glutathione and cysteine stores leads to elevated 5-oxoproline levels. N-acetylcysteine, given its effect in repleting glutathione and cysteine stores, has been proposed as a potential treatment for 5-oxoprolinemia, though reports of its successful use are lacking. We present a case of 5-oxoproline metabolic acidosis that persisted despite discontinuation of acetaminophen. However, the acidosis rapidly resolved with N-acetylcysteine administration.

High anion gap metabolic acidosis secondary to pyroglutamic aciduria (5-oxoprolinuria): association with prescription drugs and malnutrition.

PubMed

Brooker, G; Jeffery, J; Nataraj, T; Sair, M; Ayling, R

2007-07-01

Two cases of High Anion Gap Metabolic Acidosis (HAGMA) due to pyroglutamic acid (5-oxoproline) are described. In both cases the HAGMA developed during an episode of hospital treatment, in conjunction with paracetamol and antibiotic prescription, and the surviving patient made an uneventful recovery after the drugs were withdrawn. Clinicians need to be aware of this cause for metabolic acidosis because it may be a more common metabolic disturbance in compromised patients than would be expected, and the discontinuation of drugs implicated in the aetiology is therapeutic.

Effects of Hypercapnia and Hypercapnic Acidosis on Hospital Mortality in Mechanically Ventilated Patients.

PubMed

Tiruvoipati, Ravindranath; Pilcher, David; Buscher, Hergen; Botha, John; Bailey, Michael

2017-07-01

Lung-protective ventilation is used to prevent further lung injury in patients on invasive mechanical ventilation. However, lung-protective ventilation can cause hypercapnia and hypercapnic acidosis. There are no large clinical studies evaluating the effects of hypercapnia and hypercapnic acidosis in patients requiring mechanical ventilation. Multicenter, binational, retrospective study aimed to assess the impact of compensated hypercapnia and hypercapnic acidosis in patients receiving mechanical ventilation. Data were extracted from the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database over a 14-year period where 171 ICUs contributed deidentified data. Patients were classified into three groups based on a combination of pH and carbon dioxide levels (normocapnia and normal pH, compensated hypercapnia [normal pH with elevated carbon dioxide], and hypercapnic acidosis) during the first 24 hours of ICU stay. Logistic regression analysis was used to identify the independent association of hypercapnia and hypercapnic acidosis with hospital mortality. Nil. A total of 252,812 patients (normocapnia and normal pH, 110,104; compensated hypercapnia, 20,463; and hypercapnic acidosis, 122,245) were included in analysis. Patients with compensated hypercapnia and hypercapnic acidosis had higher Acute Physiology and Chronic Health Evaluation III scores (49.2 vs 53.2 vs 68.6; p < 0.01). The mortality was higher in hypercapnic acidosis patients when compared with other groups, with the lowest mortality in patients with normocapnia and normal pH. After adjusting for severity of illness, the adjusted odds ratio for hospital mortality was higher in hypercapnic acidosis patients (odds ratio, 1.74; 95% CI, 1.62-1.88) and compensated hypercapnia (odds ratio, 1.18; 95% CI, 1.10-1.26) when compared with patients with normocapnia and normal pH (p < 0.001). In patients with hypercapnic acidosis, the mortality increased with increasing PCO2 until 65 mm Hg after which the mortality plateaued. Hypercapnic acidosis during the first 24 hours of intensive care admission is more strongly associated with increased hospital mortality than compensated hypercapnia or normocapnia.

Rumen microbial and fermentation characteristics are affected differently by bacterial probiotic supplementation during induced lactic and subacute acidosis in sheep.

PubMed

Lettat, Abderzak; Nozière, Pierre; Silberberg, Mathieu; Morgavi, Diego P; Berger, Claudette; Martin, Cécile

2012-07-19

Ruminal disbiosis induced by feeding is the cause of ruminal acidosis, a digestive disorder prevalent in high-producing ruminants. Because probiotic microorganisms can modulate the gastrointestinal microbiota, propionibacteria- and lactobacilli-based probiotics were tested for their effectiveness in preventing different forms of acidosis. Lactic acidosis, butyric and propionic subacute ruminal acidosis (SARA) were induced by feed chalenges in three groups of four wethers intraruminally dosed with wheat, corn or beet pulp. In each group, wethers were either not supplemented (C) or supplemented with Propionibacterium P63 alone (P) or combined with L. plantarum (Lp + P) or L. rhamnosus (Lr + P). Compared with C, all the probiotics stimulated lactobacilli proliferation, which reached up to 25% of total bacteria during wheat-induced lactic acidosis. This induced a large increase in lactate concentration, which decreased ruminal pH. During the corn-induced butyric SARA, Lp + P decreased Prevotella spp. proportion with a concomitant decrease in microbial amylase activity and total volatile fatty acids concentration, and an increase in xylanase activity and pH. Relative to the beet pulp-induced propionic SARA, P and Lr + P improved ruminal pH without affecting the microbial or fermentation characteristics. Regardless of acidosis type, denaturing gradient gel electrophoresis revealed that probiotic supplementations modified the bacterial community structure. This work showed that the effectiveness of the bacterial probiotics tested depended on the acidosis type. Although these probiotics were ineffective in lactic acidosis because of a deeply disturbed rumen microbiota, some of the probiotics tested may be useful to minimize the occurrence of butyric and propionic SARA in sheep. However, their modes of action need to be further investigated.

Rumen microbial and fermentation characteristics are affected differently by bacterial probiotic supplementation during induced lactic and subacute acidosis in sheep

PubMed Central

2012-01-01

Background Ruminal disbiosis induced by feeding is the cause of ruminal acidosis, a digestive disorder prevalent in high-producing ruminants. Because probiotic microorganisms can modulate the gastrointestinal microbiota, propionibacteria- and lactobacilli-based probiotics were tested for their effectiveness in preventing different forms of acidosis. Results Lactic acidosis, butyric and propionic subacute ruminal acidosis (SARA) were induced by feed chalenges in three groups of four wethers intraruminally dosed with wheat, corn or beet pulp. In each group, wethers were either not supplemented (C) or supplemented with Propionibacterium P63 alone (P) or combined with L. plantarum (Lp + P) or L. rhamnosus (Lr + P). Compared with C, all the probiotics stimulated lactobacilli proliferation, which reached up to 25% of total bacteria during wheat-induced lactic acidosis. This induced a large increase in lactate concentration, which decreased ruminal pH. During the corn-induced butyric SARA, Lp + P decreased Prevotella spp. proportion with a concomitant decrease in microbial amylase activity and total volatile fatty acids concentration, and an increase in xylanase activity and pH. Relative to the beet pulp-induced propionic SARA, P and Lr + P improved ruminal pH without affecting the microbial or fermentation characteristics. Regardless of acidosis type, denaturing gradient gel electrophoresis revealed that probiotic supplementations modified the bacterial community structure. Conclusion This work showed that the effectiveness of the bacterial probiotics tested depended on the acidosis type. Although these probiotics were ineffective in lactic acidosis because of a deeply disturbed rumen microbiota, some of the probiotics tested may be useful to minimize the occurrence of butyric and propionic SARA in sheep. However, their modes of action need to be further investigated. PMID:22812531

Medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome.

PubMed

Karunarathne, Suneth; Udayakumara, Yapa; Govindapala, Dumitha; Fernando, Harshini

2012-07-26

Medullary nephrocalcinosis and distal renal tubular acidosis are closely associated and each can lead to the other. These clinical entities are rare in patients with nephrotic syndrome and polycythaemia is an unusual finding in such patients. We describe the presence of medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome due to minimal change disease. Proposed mechanisms of polycythaemia in patients with nephrotic syndrome and distal renal tubular acidosis include, increased erythropoietin production and secretion of interleukin 8 which in turn stimulate erythropoiesis. A 22 year old Sri Lankan Sinhala male with nephrotic syndrome due to minimal change disease was investigated for incidentally detected polycythaemia. Investigations revealed the presence of renal tubular acidosis type I and medullary nephrocalcinosis. Despite extensive investigation, a definite cause for polycythaemia was not found in this patient. Treatment with potassium and bicarbonate supplementation with potassium citrate led to correction of acidosis thereby avoiding the progression of nephrocalcinosis and harmful effects of chronic acidosis. The constellation of clinical and biochemical findings in this patient is unique but the pathogenesis of erythrocytosis is not clearly explained. The proposed mechanisms for erythrocytosis in other patients with proteinuria include increased erythropoietin secretion due to renal hypoxia and increased secretion of interleukin 8 from the kidney. This case illustrates that there may exist hitherto unknown connections between tubular and glomerular dysfunction in patients with nephrotic syndrome.

Metabolic acidosis caused by concomitant use of paracetamol (acetaminophen) and flucloxacillin? A case report and a retrospective study.

PubMed

Berbee, J K; Lammers, L A; Krediet, C T P; Fischer, J C; Kemper, E M

2017-11-01

A patient was identified with severe metabolic acidosis, a high anion gap and 5-oxoproline accumulation, probably caused by the simultaneous use of paracetamol (acetaminophen) and flucloxacillin. We wanted to investigate the necessity to control the interaction between both drugs with an automatic alert system. To investigate the relevance of the interaction of paracetamol and flucloxacillin, a retrospective study was conducted. Data on paracetamol and flucloxacillin prescriptions and laboratory data (pH, Na + , HCO 3 - , Cl - , albumin and 5-oxoproline levels) were combined to assess the prevalence of acidosis, calculate the anion gap and analyse 5-oxoproline levels in clinically admitted patients using both drugs simultaneously. In the 2-year study period, approximately 53,000 admissions took place in our hospital. One thousand and fifty-seven patients used paracetamol and flucloxacillin simultaneously, of which 51 patients (4.8%) had a serum pH ≤ 7.35. One patient, the same patient as presented in the case report, had a high anion gap and a toxic level of 5-oxoproline. The prevalence of metabolic acidosis is very low and the only patient identified with the interaction was recognised during normal clinical care. We conclude that automatic alerts based on simultaneous use of paracetamol and flucloxacillin will generate too many signals. To recognise patients earlier and prevent severe outcomes, a warning system (clinical rule) based on paracetamol, flucloxacillin and pH measurement may be helpful. Early calculation of the anion gap can narrow the differential diagnosis of patients with metabolic acidosis and measurement of 5-oxoproline can explain acidosis due the interaction of paracetamol and flucloxacillin.

Rapid review shows that probiotics and fermented infant formulas do not cause d-lactic acidosis in healthy children.

PubMed

Łukasik, J; Salminen, S; Szajewska, H

2018-03-30

Extensive ongoing research on probiotics and infant formulas raises a number of safety questions. One concern is the potential influence of d-lactic acid-containing preparations on the health of infants and children. The aim of this review was to summarise the available knowledge on the ingestion of d-lactic acid-producing bacteria, acidified infant formulas and fermented infant formulas as a potential cause of paediatric d-lactic acidosis. A Medline database search was performed in July 2017, with no restrictions on the language, article type or publication date. The 1715 search results were screened for clinical trials, review articles, case series and case reports of relevance to the topic. We identified five randomised controlled trials from 2005 to 2017 covering 544 healthy infants and some case reports and experimental studies. No clinically relevant adverse effects of d-lactic acid-producing probiotics and fermented infant formulas were described in healthy children. However, a harmless, subclinical accumulation of d-lactate was theoretically possible. The only known cases of paediatric d-lactic acidosis occurred in patients with short bowel syndrome or, historically, in infants fed with acidified formulas. Our main finding was that probiotics and fermented formulas did not cause d-lactic acidosis in healthy children. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Regulatory mechanisms of hemoglobin oxygen affinity in acidosis and alkalosis

PubMed Central

Bellingham, A. J.; Detter, J. C.; Lenfant, C.

1971-01-01

The recent reports of the effect of 2,3-diphosphoglycerate (2,3-DPG) on hemoglobin affinity for oxygen suggested that this substance may play a role in man's adaptation to acidosis and alkalosis. A study of the effect of induced acidosis and alkalosis on the oxyhemoglobin dissociation curve of normal man was therefore carried out, and the mechanisms involved in the physiological regulation of hemoglobin oxygen affinity examined. In acute changes of plasma pH there was no alteration in red cell 2,3-DPG content. However, there were changes in hemoglobin oxygen affinity and these correlated with changes in mean corpuscular hemoglobin concentration (MCHC). With maintained acidosis and alkalosis, red cell 2,3-DPG content was altered and correlated with the changes in hemoglobin oxygen affinity. Both of these mechanisms shift the hemoglobin oxygen dissociation curve opposite to the direct pH (Bohr) effect, and providing the rate of pH change is neither too rapid nor too large, they counteract the direct pH effect and the in vivo hemoglobin oxygen affinity remains unchanged. It is also shown that approximately 35% of the change in hemoglobin oxygen affinity resulting from an alteration in red cell 2,3-DPG, is explained by effect of 2,3-DPG on the red cell pH. PMID:5545127

FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome.

PubMed

Dai, H; Zhang, V W; El-Hattab, A W; Ficicioglu, C; Shinawi, M; Lines, M; Schulze, A; McNutt, M; Gotway, G; Tian, X; Chen, S; Wang, J; Craigen, W J; Wong, L-J

2017-04-01

Mutations in FBXL4 have recently been recognized to cause a mitochondrial disorder, with clinical features including early onset lactic acidosis, hypotonia, and developmental delay. FBXL4 sequence analysis was performed in 808 subjects suspected to have a mitochondrial disorder. In addition, 28 samples from patients with early onset of lactic acidosis, but without identifiable mutations in 192 genes known to cause mitochondrial diseases, were examined for FBXL4 mutations. Definitive diagnosis was made in 10 new subjects with a total of 7 novel deleterious variants; 5 null and 2 missense substitutions. All patients exhibited congenital lactic acidemia, most of them with severe encephalopathic presentation, and global developmental delay. Overall, FBXL4 defects account for at least 0.7% (6 out of 808) of subjects suspected to have a mitochondrial disorder, and as high as 14.3% (4 out of 28) in young children with congenital lactic acidosis and clinical features of mitochondrial disease. Including FBLX4 in the mitochondrial diseases panel should be particularly important for patients with congenital lactic acidosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acidosis Activates Endoplasmic Reticulum Stress Pathways through GPR4 in Human Vascular Endothelial Cells

PubMed Central

Dong, Lixue; Krewson, Elizabeth A.; Yang, Li V.

2017-01-01

Acidosis commonly exists in the tissue microenvironment of various pathophysiological conditions such as tumors, inflammation, ischemia, metabolic disease, and respiratory disease. For instance, the tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (the “Warburg effect”), and the defective vasculature that cannot efficiently deliver oxygen and nutrients or remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined. GPR4 (G protein-coupled receptor 4) is a member of the proton-sensing G protein-coupled receptors and it has high expression in endothelial cells (ECs). We have previously reported that acidosis induces a broad inflammatory response in ECs. Acidosis also increases the expression of several endoplasmic reticulum (ER) stress response genes such as CHOP (C/EBP homologous protein) and ATF3 (activating transcription factor 3). In the current study, we have examined acidosis/GPR4-induced ER stress pathways in human umbilical vein endothelial cells (HUVEC) and other types of ECs. All three arms of the ER stress/unfolded protein response (UPR) pathways were activated by acidosis in ECs as an increased expression of phosphorylated eIF2α (eukaryotic initiation factor 2α), phosphorylated IRE1α (inositol-requiring enzyme 1α), and cleaved ATF6 upon acidic pH treatment was observed. The expression of other downstream mediators of the UPR, such as ATF4, ATF3, and spliced XBP-1 (X box-binding protein 1), was also induced by acidosis. Through genetic and pharmacological approaches to modulate the expression level or activity of GPR4 in HUVEC, we found that GPR4 plays an important role in mediating the ER stress response induced by acidosis. As ER stress/UPR can cause inflammation and cell apoptosis, acidosis/GPR4-induced ER stress pathways in ECs may regulate vascular growth and inflammatory response in the acidic microenvironment. PMID:28134810

Acidosis Activates Endoplasmic Reticulum Stress Pathways through GPR4 in Human Vascular Endothelial Cells.

PubMed

Dong, Lixue; Krewson, Elizabeth A; Yang, Li V

2017-01-27

Acidosis commonly exists in the tissue microenvironment of various pathophysiological conditions such as tumors, inflammation, ischemia, metabolic disease, and respiratory disease. For instance, the tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (the "Warburg effect"), and the defective vasculature that cannot efficiently deliver oxygen and nutrients or remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined. GPR4 (G protein-coupled receptor 4) is a member of the proton-sensing G protein-coupled receptors and it has high expression in endothelial cells (ECs). We have previously reported that acidosis induces a broad inflammatory response in ECs. Acidosis also increases the expression of several endoplasmic reticulum (ER) stress response genes such as CHOP (C/EBP homologous protein) and ATF3 (activating transcription factor 3). In the current study, we have examined acidosis/GPR4- induced ER stress pathways in human umbilical vein endothelial cells (HUVEC) and other types of ECs. All three arms of the ER stress/unfolded protein response (UPR) pathways were activated by acidosis in ECs as an increased expression of phosphorylated eIF2α (eukaryotic initiation factor 2α), phosphorylated IRE1α (inositol-requiring enzyme 1α), and cleaved ATF6 upon acidic pH treatment was observed. The expression of other downstream mediators of the UPR, such as ATF4, ATF3, and spliced XBP-1 (X box-binding protein 1), was also induced by acidosis. Through genetic and pharmacological approaches to modulate the expression level or activity of GPR4 in HUVEC, we found that GPR4 plays an important role in mediating the ER stress response induced by acidosis. As ER stress/UPR can cause inflammation and cell apoptosis, acidosis/GPR4-induced ER stress pathways in ECs may regulate vascular growth and inflammatory response in the acidic microenvironment.

Diagnosis and management of severe respiratory acidosis: a 65-year-old man with a double-lung transplant and shortness of breath.

PubMed

Adrogué, Horacio J

2010-11-01

Respiratory acidosis is characterized by a primary increase in whole-body carbon dioxide stores caused by a positive carbon dioxide balance. This acid-base disorder, if severe, may be life-threatening, therefore requiring prompt recognition and expert management. The case presented highlights the essential features of the diagnosis and management of respiratory acidosis. A brief description of the modifiers of carbon dioxide production, the pathogenesis of respiratory acidosis, and an algorithm for assessment and management of this disorder is included. Key teaching points include the clinical value of both arterial and venous blood gas analyses and the importance of proper recognition of a primary respiratory arrest in contrast to primary circulatory arrest when managing a patient who requires resuscitation from "cardiorespiratory arrest." Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

[Lactic acidosis in the postictal state].

PubMed

van Rooij, Femke J M; Admiraal-van de Pas, Yvonne

2015-01-01

Epilepsy is a neurological disorder with an annual incidence in the Netherlands of 30 per 100,000 people. We present two cases of a patient admitted to the emergency department upon experiencing a generalized seizure. In each case, severe metabolic lactic acidosis was identified through routine laboratory diagnostics. Based on their clinical presentation, we had no reasons to suspect another cause of this severe acidosis apart from the seizure. We repeated arterial blood sample one to two hours later and found that both pH and lactate were normalized. Severe lactic acidosis may occur in patients who experience seizures but otherwise do not require treatment. Taking an arterial blood sample from these patients in the emergency setting will be of limited value, because in most patients hyperlactatemia in the postictal state is self-limiting. In some patients, however, a persistent hyperlactatemia may indicate a serious underlying pathology. It is therefore advisable to repeat an arterial blood sample a few hours later.

Lactic Acidosis Induced by Linezolid Mimics Symptoms of an Acute Intracranial Bleed: A Case Report and Literature Review.

PubMed

Zuccarini, Nichole Suzzanne; Yousuf, Tariq; Wozniczka, Daniel; Rauf, Anis Abdul

2016-10-01

Lactic acidosis is common and most often associated with disturbed acid-base balance. Rarely, it can be a life-threatening medication side effect. Hence, determining the etiology of lactic acidosis early in patients is paramount in choosing the correct therapeutic intervention. Although lactic acidosis as an adverse drug reaction of linezolid is a well-recognized and documented clinical entity, the occurrence of such mimicking an acute intracranial bleed has not been reported to our knowledge. The following case is presented as an example of such an occurrence. A 67-year-old woman presented to the emergency department for lethargy, nausea and syncope. The head CT did not demonstrate any bleeding or mass effect, but lab results were significant for elevated lactic acid. The patient recently underwent left total hip replacement surgery, which was complicated by a methicillin-resistant Staphylococcus aureus (MRSA) infection. She received 6 weeks of oral linezolid therapy. And upon learning that key part of her history, the linezolid was discontinued. Her lactic acid rapidly normalized and she was discharged home. Several publications demonstrate that linezolid induces lactic acidosis by disrupting crucial mitochondrial functions. It is essential that clinicians are aware that linezolid can cause lactic acidosis. And, the important reminder is that adverse drug reactions can often mimic common diseases. If it is not recognized early, ominous clinical consequences may occur. In conclusion, linezolid should be suspected and included in the differential diagnosis if lactic acidosis exists with an uncommon clinical picture.

[Case of distal renal tubular acidosis complicated with renal diabetes insipidus, showing aggravation of symptoms with occurrence of diabetes mellitus].

PubMed

Liu, Hexing; Tomoda, Fumihiro; Koike, Tsutomu; Ohara, Maiko; Nakagawa, Taizo; Kagitani, Satoshi; Inoue, Hiroshi

2011-01-01

We report herein a 27-year-old male case of inherited distal renal tubular acidosis complicated with renal diabetes insipidus, the symptoms of which were aggravated by the occurrence of diabetes mellitus. At 2 months after birth, he was diagnosed as having inherited distal renal tubular acidosis and thereafter supplementation of both potassium and alkali was started to treat his hypokalemia and metabolic acidosis. At the age of 4 years, calcification of the bilateral renal medulla was detected by computed tomography. Subsequently his urinary volume gradually increased and polyuria of approximately 4 L/day persisted. At the age of 27 years, he became fond of sugar-sweetened drinks and also often forgot to take the medicine. He was admitted to our hospital due to polyuria of more than 10 L day, muscle weakness and gait disturbance. Laboratory tests disclosed worsening of both hypokalemia and metabolic acidosis in addition to severe hyperglycemia. It seemed likely that occurrence of diabetes mellitus and cessation of medications can induce osmotic diuresis and aggravate hypokalemia and metabolic acidosis. Consequently, severe dehydration, hypokalemia-induced damage of his urinary concentration ability and enhancement of the renin angiotensin system occurred and thereby possibly worsened his hypokalemia and metabolic acidosis. As normalization of hyperglycemia and metabolic acidosis might have exacerbated hypokalemia further, dehydration and hypokalemia were treated first. Following intensive treatment, these abnormalities were improved, but polyuria persisted. Elevated plasma antidiuretic hormone (12.0 pg/mL) and deficit of renal responses to antidiuretic hormone suggested that the polyuria was attributable to the preexisting renal diabetes insipidus possibly caused by bilateral renal medulla calcification. Thiazide diuretic or nonsteroidal anti-inflammatory drugs were not effective for the treatment of diabetes insipidus in the present case.

Furosemide/Fludrocortisone Test and Clinical Parameters to Diagnose Incomplete Distal Renal Tubular Acidosis in Kidney Stone Formers.

PubMed

Dhayat, Nasser A; Gradwell, Michael W; Pathare, Ganesh; Anderegg, Manuel; Schneider, Lisa; Luethi, David; Mattmann, Cedric; Moe, Orson W; Vogt, Bruno; Fuster, Daniel G

2017-09-07

Incomplete distal renal tubular acidosis is a well known cause of calcareous nephrolithiasis but the prevalence is unknown, mostly due to lack of accepted diagnostic tests and criteria. The ammonium chloride test is considered as gold standard for the diagnosis of incomplete distal renal tubular acidosis, but the furosemide/fludrocortisone test was recently proposed as an alternative. Because of the lack of rigorous comparative studies, the validity of the furosemide/fludrocortisone test in stone formers remains unknown. In addition, the performance of conventional, nonprovocative parameters in predicting incomplete distal renal tubular acidosis has not been studied. We conducted a prospective study in an unselected cohort of 170 stone formers that underwent sequential ammonium chloride and furosemide/fludrocortisone testing. Using the ammonium chloride test as gold standard, the prevalence of incomplete distal renal tubular acidosis was 8%. Sensitivity and specificity of the furosemide/fludrocortisone test were 77% and 85%, respectively, yielding a positive predictive value of 30% and a negative predictive value of 98%. Testing of several nonprovocative clinical parameters in the prediction of incomplete distal renal tubular acidosis revealed fasting morning urinary pH and plasma potassium as the most discriminative parameters. The combination of a fasting morning urinary threshold pH <5.3 with a plasma potassium threshold >3.8 mEq/L yielded a negative predictive value of 98% with a sensitivity of 85% and a specificity of 77% for the diagnosis of incomplete distal renal tubular acidosis. The furosemide/fludrocortisone test can be used for incomplete distal renal tubular acidosis screening in stone formers, but an abnormal furosemide/fludrocortisone test result needs confirmation by ammonium chloride testing. Our data furthermore indicate that incomplete distal renal tubular acidosis can reliably be excluded in stone formers by use of nonprovocative clinical parameters. Copyright © 2017 by the American Society of Nephrology.

Analysis of the clinical backgrounds of patients who developed respiratory acidosis under high-flow oxygen therapy during emergency transport.

PubMed

Ogino, Hirokazu; Nishimura, Naoki; Yamano, Yasuhiko; Ishikawa, Genta; Tomishima, Yutaka; Jinta, Torahiko; Takahashi, Osamu; Chohnabayashi, Naohiko

2016-01-01

High-flow oxygen is often administered to patients during emergency transport and can sometimes cause respiratory acidosis with disturbed consciousness, thereby necessitating mechanical ventilation. Although oxygen titration in chronic obstructive pulmonary disease patients during emergency transport reduces mortality rates, the clinical risk factors for respiratory acidosis in emergency settings are not fully understood. Therefore, we analyzed the clinical backgrounds of patients who developed respiratory acidosis during pre-hospital transport. This was a retrospective study of patients who arrived at our hospital by emergency transport in 2010 who received high-flow oxygen while in transit. Respiratory acidosis was defined by the following arterial blood gas readings: pH, ≤7.35; PaCO 2 , ≥45 mmHg; and HCO 3 - , ≥24 mmol/L. The risk factors were identified using multivariable logistic regression analysis. In 765 study patients, 66 patients showed respiratory acidosis. The following risk factors for respiratory acidosis were identified: age, ≥65 years (odds ratio [OR] 1.4; 95% confidence interval [CI], 0.7-2.8); transportation time, ≥10 min (OR 2.0; 95% CI, 1.1-3.7); three digits on the Japan Coma Scale (OR 3.1; 95% CI, 1.7-5.8); percutaneous oxygen saturation, ≤90% (OR 1.6; 95% CI, 0.8-3.0); tuberculosis (OR 4.5; 95% CI, 1.4-15.1); asthma (OR 1.8; 95% CI, 0.6-5.3); pneumonia (OR 1.5; 95% CI, 0.7-3.1); and lung cancer (OR 3.9; 95% CI, 1.5-10.1). These underlying diseases as risk factors included both comorbid diseases and past medical conditions. The factors identified may contribute to the development of respiratory acidosis. Further studies on preventing respiratory acidosis will improve the quality of emergency medical care.

Analysis of the clinical backgrounds of patients who developed respiratory acidosis under high‐flow oxygen therapy during emergency transport

PubMed Central

Ogino, Hirokazu; Yamano, Yasuhiko; Ishikawa, Genta; Tomishima, Yutaka; Jinta, Torahiko; Takahashi, Osamu; Chohnabayashi, Naohiko

2015-01-01

Aim High‐flow oxygen is often administered to patients during emergency transport and can sometimes cause respiratory acidosis with disturbed consciousness, thereby necessitating mechanical ventilation. Although oxygen titration in chronic obstructive pulmonary disease patients during emergency transport reduces mortality rates, the clinical risk factors for respiratory acidosis in emergency settings are not fully understood. Therefore, we analyzed the clinical backgrounds of patients who developed respiratory acidosis during pre‐hospital transport. Methods This was a retrospective study of patients who arrived at our hospital by emergency transport in 2010 who received high‐flow oxygen while in transit. Respiratory acidosis was defined by the following arterial blood gas readings: pH, ≤7.35; PaCO 2, ≥45 mmHg; and HCO 3 −, ≥24 mmol/L. The risk factors were identified using multivariable logistic regression analysis. Results In 765 study patients, 66 patients showed respiratory acidosis. The following risk factors for respiratory acidosis were identified: age, ≥65 years (odds ratio [OR] 1.4; 95% confidence interval [CI], 0.7–2.8); transportation time, ≥10 min (OR 2.0; 95% CI, 1.1–3.7); three digits on the Japan Coma Scale (OR 3.1; 95% CI, 1.7–5.8); percutaneous oxygen saturation, ≤90% (OR 1.6; 95% CI, 0.8–3.0); tuberculosis (OR 4.5; 95% CI, 1.4–15.1); asthma (OR 1.8; 95% CI, 0.6–5.3); pneumonia (OR 1.5; 95% CI, 0.7–3.1); and lung cancer (OR 3.9; 95% CI, 1.5–10.1). These underlying diseases as risk factors included both comorbid diseases and past medical conditions. Conclusions The factors identified may contribute to the development of respiratory acidosis. Further studies on preventing respiratory acidosis will improve the quality of emergency medical care. PMID:29123744

Diagnosis and Treatment of Metabolic Acidosis in Patients with Chronic Kidney Disease - Position Statement of the Working Group of the Polish Society of Nephrology.

PubMed

Adamczak, Marcin; Masajtis-Zagajewska, Anna; Mazanowska, Oktawia; Madziarska, Katarzyna; Stompór, Tomasz; Więcek, Andrzej

2018-01-01

Metabolic acidosis is commonly found in patients with chronic kidney disease (CKD), and its causes are: impaired ammonia excretion, reduced tubular bicarbonate reabsorption and insufficient renal bicarbonate production in relation to the amount of acids synthesised by the body and ingested with food. As the consequence, numerous metabolic abnormalities develop, which may lead to dysfunction of several organs. In observational studies, it has been found that CKD patients with metabolic acidosis are characterised by faster progression of kidney disease towards end stage kidney failure, and by increased mortality. Results of interventional studies suggest that alkali therapy in CKD patients slows progression of kidney disease. In view of these facts, the members of "The Working Group of the Polish Society of Nephrology on Metabolic and Endocrine Abnormalities in Kidney Diseases" have prepared the following statement and guidelines for the diagnosis and treatment of metabolic acidosis in CKD patients. Measurement of bicarbonate concentration in venous plasma or venous blood to check for metabolic acidosis should be performed in all CKD patients and metabolic acidosis in these patients should be diagnosed when the venous plasma or venous blood bicarbonate concentration is lower than 22 mmol/l. In patients with metabolic acidosis and CKD, oral sodium bicarbonate administration is recommended. The goal of such a treatment is to achieve a plasma or blood bicarbonate concentration equal to or greater than 22 mmol/l. © 2018 The Author(s). Published by S. Karger AG, Basel.

Acidosis mediates recurrent hypoglycemia-induced increase in ischemic brain injury in treated diabetic rats.

PubMed

Rehni, Ashish K; Shukla, Vibha; Perez-Pinzon, Miguel A; Dave, Kunjan R

2018-03-15

Cerebral ischemia is a serious possible manifestation of diabetic vascular disease. Recurrent hypoglycemia (RH) enhances ischemic brain injury in insulin-treated diabetic (ITD) rats. In the present study, we determined the role of ischemic acidosis in enhanced ischemic brain damage in RH-exposed ITD rats. Diabetic rats were treated with insulin and mild/moderate RH was induced for 5 days. Three sets of experiments were performed. The first set evaluated the effects of RH exposure on global cerebral ischemia-induced acidosis in ITD rats. The second set evaluated the effect of an alkalizing agent (Tris-(hydroxymethyl)-aminomethane: THAM) on ischemic acidosis-induced brain injury in RH-exposed ITD rats. The third experiment evaluated the effect of the glucose transporter (GLUT) inhibitor on ischemic acidosis-induced brain injury in RH-exposed ITD rats. Hippocampal pH and lactate were measured during ischemia and early reperfusion for all three experiments. Neuronal survival in Cornu Ammonis 1 (CA1) hippocampus served as a measure of ischemic brain injury. Prior RH exposure increases lactate concentration and decreases pH during ischemia and early reperfusion when compared to controls. THAM and GLUT inhibitor treatments attenuated RH-induced increase in ischemic acidosis. GLUT inhibitor treatment reduced the RH-induced increase in lactate levels. Both THAM and GLUT inhibitor treatments significantly decreased ischemic damage in RH-exposed ITD rats. Ischemia causes increased acidosis in RH-exposed ITD rats via a GLUT-sensitive mechanism. Exploring downstream pathways may help understand mechanisms by which prior exposure to RH increases cerebral ischemic damage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Respiratory gas exchange as a new aid to monitor acidosis in endotoxemic rats: relationship to metabolic fuel substrates and thermometabolic responses.

PubMed

Steiner, Alexandre A; Flatow, Elizabeth A; Brito, Camila F; Fonseca, Monique T; Komegae, Evilin N

2017-01-01

This study introduces the respiratory exchange ratio (RER; the ratio of whole-body CO 2 production to O 2 consumption) as an aid to monitor metabolic acidosis during the early phase of endotoxic shock in unanesthetized, freely moving rats. Two serotypes of lipopolysaccharide (lipopolysaccharide [LPS] O55:B5 and O127:B8) were tested at shock-inducing doses (0.5-2 mg/kg). Phasic rises in RER were observed consistently across LPS serotypes and doses. The RER rise often exceeded the ceiling of the quotient for oxidative metabolism, and was mirrored by depletion of arterial bicarbonate and decreases in pH It occurred independently of ventilatory adjustments. These data indicate that the rise in RER results from a nonmetabolic CO 2 load produced via an acid-induced equilibrium shift in the bicarbonate buffer. Having validated this new experimental aid, we asked whether acidosis was interconnected with the metabolic and thermal responses that accompany endotoxic shock in unanesthetized rats. Contrary to this hypothesis, however, acidosis persisted regardless of whether the ambient temperature favored or prevented downregulation of mitochondrial oxidation and regulated hypothermia. We then asked whether the substrate that fuels aerobic metabolism could be a relevant factor in LPS-induced acidosis. Food deprivation was employed to divert metabolism away from glucose oxidation and toward fatty acid oxidation. Interestingly, this intervention attenuated the RER response to LPS by 58%, without suppressing other key aspects of systemic inflammation. We conclude that acid production in unanesthetized rats with endotoxic shock results from a phasic activation of glycolysis, which occurs independently of physiological changes in mitochondrial oxidation and body temperature. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

LACTIC ACIDOSIS: A RARE MANIFESTATION OF SYNTHETIC MARIJUANA INTOXICATION.

PubMed

Antill, T; Jakkoju, A; Dieguez, J; Laskhmiprasad, L

2015-01-01

Synthetic cannabinoids are designer drugs that mimic the effect of cannabis, which has become popular with young drug users. These drugs have a similar chemical structure and pharmacologic effects as marijuana, but seem to be more potent. These substances have been banned by the US Drug Enforcement Agency in 2010. Prior to 2010, these drugs were perceived as "safer" by the general population. Synthetic cannabinoids cause effects similar to marijuana making the subjects euphoric. However, they act as full, rather than partial, agonist at the receptor sites causing more severe side effects such as severe agitation, seizures, acute renal failure, and lactic acidosis.

Rickets–vitamin D deficiency and dependency

PubMed Central

Sahay, Manisha; Sahay, Rakesh

2012-01-01

Rickets is an important problem even in countries with adequate sun exposure. The causes of rickets/osteomalacia are varied and include nutritional deficiency, especially poor dietary intake of vitamin D and calcium. Non-nutritional causes include hypophosphatemic rickets primarily due to renal phosphate losses and rickets due to renal tubular acidosis. In addition, some varieties are due to inherited defects in vitamin D metabolism and are called vitamin D dependent rickets. This chapter highlights rickets/osteomalacia related to vitamin D deficiency or to inherited defects in vitamin D metabolism. Hypophosphatemic rickets and rickets due to renal tubular acidosis are discussed in other sections of the journal. PMID:22470851

Comprehensive clinical approach to renal tubular acidosis.

PubMed

Sharma, Sonia; Gupta, Ankur; Saxena, Sanjiv

2015-08-01

Renal tubular acidosis (RTA) is essentially characterized by normal anion gap and hyperchloremic metabolic acidosis. It is important to understand that despite knowing the disease for 60-70 years, complexities in the laboratory tests and their interpretation still make clinicians cautious to diagnose and label types of tubular disorder. Hence, we are writing this mini-review to emphasize on the step wise approach to RTA with some understanding on its basic etiopathogenesis. This will definitely help to have an accurate interpretation of urine and blood reports in correlation with the clinical condition. RTA can be a primary or secondary defect and results either due to abnormality in bicarbonate ion absorption or hydrogen ion secretion. Primary defects are common in children due to gene mutation or idiopathic nature while secondary forms are more common in adults. We are focusing and explaining here in this review all the clinical and laboratory parameters which are essential for making the diagnosis of RTA and excluding the extrarenal causes of hyperchloremic, normal anion gap metabolic acidosis.

Citrate metabolism in blood transfusions and its relationship due to metabolic alkalosis and respiratory acidosis

PubMed Central

Li, Kai; Xu, Yuan

2015-01-01

Metabolic alkalosis commonly results from excessive hydrochloric acid (HCl), potassium (K+) and water (H2O) loss from the stomach or through the urine. The plasma anion gap increases in non-hypoproteinemic metabolic alkalosis due to an increased negative charge equivalent on albumin and the free ionized calcium (Ca++) content of plasma decreases. The mean citrate load in all patients was 8740±7027 mg from 6937±6603 mL of transfused blood products. The citrate load was significantly higher in patients with alkalosis (9164±4870 vs. 7809±3967, P < 0.05). The estimated mean total citrate administered via blood and blood products was calculated as 43.2±34.19 mg/kilogram/day. In non-massive and frequent blood transfusions, the elevated carbon dioxide output has been shown to occur. Due to citrate metabolism causes intracellular acidosis. As a result of intracellular acidosis compensation, decompensated metabolic alkalosis + respiratory acidosis and electrolyte imbalance may develop, blood transfusions may result in certain complications. PMID:26131288

Citrate metabolism in blood transfusions and its relationship due to metabolic alkalosis and respiratory acidosis.

PubMed

Li, Kai; Xu, Yuan

2015-01-01

Metabolic alkalosis commonly results from excessive hydrochloric acid (HCl), potassium (K(+)) and water (H2O) loss from the stomach or through the urine. The plasma anion gap increases in non-hypoproteinemic metabolic alkalosis due to an increased negative charge equivalent on albumin and the free ionized calcium (Ca(++)) content of plasma decreases. The mean citrate load in all patients was 8740±7027 mg from 6937±6603 mL of transfused blood products. The citrate load was significantly higher in patients with alkalosis (9164±4870 vs. 7809±3967, P < 0.05). The estimated mean total citrate administered via blood and blood products was calculated as 43.2±34.19 mg/kilogram/day. In non-massive and frequent blood transfusions, the elevated carbon dioxide output has been shown to occur. Due to citrate metabolism causes intracellular acidosis. As a result of intracellular acidosis compensation, decompensated metabolic alkalosis + respiratory acidosis and electrolyte imbalance may develop, blood transfusions may result in certain complications.

Diffuse Lymphomatous Infiltration of Kidney Presenting as Renal Tubular Acidosis and Hypokalemic Paralysis: Case Report

PubMed Central

Jhamb, Rajat; Gupta, Naresh; Garg, Sandeep; Kumar, Sachin; Gulati, Sameer; Mishra, Deepak; Beniwal, Pankaj

2007-01-01

We report the case of a 22-year-old woman who presented with acute onset flaccid quadriparesis. Physical examination showed mild pallor with cervical and axillary lymphadenopathy, hepatomegaly, and bilateral smooth enlarged kidneys. Neurological examination revealed lower motor neuron muscle weakness in all the four limbs with hyporeflexia and normal sensory examination. Laboratory investigations showed anemia, severe hypokalemia, and metabolic acidosis. Urinalysis showed a specific gravity of 1.010, pH of 7.0, with a positive urine anion gap. Ultrasound revealed hepatosplenomegaly with bilateral enlarged smooth kidneys. Renal biopsy was consistent with the diagnosis of non-Hodgkin lymphoma (B cell type). Metabolic acidosis, alkaline urine, and severe hypokalemia due to excessive urinary loss in our patient were suggestive of distal renal tubular acidosis. Renal involvement in lymphoma is usually subclinical and clinically overt renal disease is rare. Diffuse lymphomatous infiltration of the kidneys may cause tubular dysfunction and present with hypokalemic paralysis. PMID:18074421

Type 4 renal tubular acidosis in a kidney transplant recipient.

PubMed

Kulkarni, Manjunath

2016-02-01

We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim - sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment. Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.

Primary hyperparathyroidism and proximal renal tubular acidosis: Report of two cases

PubMed Central

Siddiqui, Abdullah A.; Wilson, Douglas R.

1972-01-01

Two cases of primary hyperparathyroidism due to single parathyroid adenomas presented with the additional feature of hyperchloremic acidosis. The defect in urinary acidification responsible was not of the distal or gradient-limited type since both patients could lower urine pH adequately. However, there was a defect of bicarbonate reabsorption, an abnormality referred to as the proximal or rate-limited type of renal tubular acidosis. It is suggested that this defect represents an exaggeration of the physiological effect of parathormone on bicarbonate reabsorption and may be responsible for the frequent finding of hyperchloremia in association with primary hyperparathyroidism as well as for the urinary bicarbonate-wasting associated with a variety of causes of secondary hyperparathyroidism. PMID:5012229

Atypical Strokes in a Young African American Male: A Case of Mitochondrial Encephalopathy Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome

PubMed Central

Sanchez, Jully M.; Tan, Judy Ann; Farmakiotis, Dimitrios; Aggarwal, Vikas

2011-01-01

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare but important cause of stroke-like symptoms which can often be missed Thambisetty and Newman 2004. We describe a case of a young male presenting with stroke-like episodes, later diagnosed with MELAS in an attempt to improve the understanding about diagnosing MELAS in the appropriate clinical context. PMID:21789268

[Acute confusional syndrome associated with obstructive sleep apnea aggravated by acidosis secondary to oral acetazolamide treatment].

PubMed

Miguel, E; Güell, R; Antón, A; Montiel, J A; Mayos, M

2004-06-01

Acute confusional syndrome, or delirium, is a transitory mental state characterized by the fluctuating alteration of awareness and attention levels. We present the case of a patient with acute confusional syndrome associated with obstructive sleep apnea syndrome (OSAS) aggravated by metabolic acidosis induced by oral acetazolamide treatment.A 70-year-old man with no history of neurological disease was referred with a clinical picture consistent with acute confusional syndrome presenting between midnight and dawn. During the admission examination infectious, toxic, and neurologic causes, or those related to metabolic or heart disease were ruled out. Arterial blood gases measured during one of the nighttime episodes of acute confusional syndrome showed mild hypoxia and hypercapnia with mixed acidosis. Signs and symptoms suggestive of OSAS had been developing over the months prior to admission, with snoring, sleep apnea, and moderate daytime drowsiness. Polysomnography demonstrated severe OSAS with an apnea-hypopnea index of 38. Mean arterial oxygen saturation was 83%; time oxygen saturation remained below 90% was 44%. The attending physician ordered the withdrawal of oral acetazolamide, which was considered the cause of the metabolic component of acidosis. Treatment with continuous positive airway pressure was initiated at 9 cm H2O, after a titration polysomnographic study. The patient continued to improve.OSAS, for which very effective treatment is available, should be included among diseases that may trigger acute confusional syndrome.

Effect of collecting duct-specific deletion of both Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg) on renal response to metabolic acidosis

PubMed Central

Lee, Hyun-Wook; Verlander, Jill W.; Handlogten, Mary E.; Han, Ki-Hwan

2013-01-01

The Rhesus (Rh) glycoproteins, Rh B and Rh C Glycoprotein (Rhbg and Rhcg, respectively), are ammonia-specific transporters expressed in renal distal nephron and collecting duct sites that are necessary for normal rates of ammonia excretion. The purpose of the current studies was to determine the effect of their combined deletion from the renal collecting duct (CD-Rhbg/Rhcg-KO) on basal and acidosis-stimulated acid-base homeostasis. Under basal conditions, urine pH and ammonia excretion and serum HCO3− were similar in control (C) and CD-Rhbg/Rhcg-KO mice. After acid-loading for 7 days, CD-Rhbg/Rhcg-KO mice developed significantly more severe metabolic acidosis than did C mice. Acid loading increased ammonia excretion, but ammonia excretion increased more slowly in CD-Rhbg/Rhcg-KO and it was significantly less than in C mice on days 1–5. Urine pH was significantly more acidic in CD-Rhbg/Rhcg-KO mice on days 1, 3, and 5 of acid loading. Metabolic acidosis increased phosphenolpyruvate carboxykinase (PEPCK) and Na+/H+ exchanger NHE-3 and decreased glutamine synthetase (GS) expression in both genotypes, and these changes were significantly greater in CD-Rhbg/Rhcg-KO than in C mice. We conclude that 1) Rhbg and Rhcg are critically important in the renal response to metabolic acidosis; 2) the significantly greater changes in PEPCK, NHE-3, and GS expression in acid-loaded CD-Rhbg/Rhcg-KO compared with acid-loaded C mice cause the role of Rhbg and Rhcg to be underestimated quantitatively; and 3) in mice with intact Rhbg and Rhcg expression, metabolic acidosis does not induce maximal changes in PEPCK, NHE-3, and GS expression despite the presence of persistent metabolic acidosis. PMID:24338819

Trimethoprim/Sulfamethoxazole-Induced Severe Lactic Acidosis: A Case Report and Review of the Literature.

PubMed

Bulathsinghala, Marie; Keefer, Kimberly; Van de Louw, Andry

2016-04-01

Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG.A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid-base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity.Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX.

Effects of Intragastric and Intravenous Sodium Bicarbonate on Rate of Recovery from Post-asphyxial Acidosis in the Neonate

PubMed Central

Evans, R. S.; Olver, R. E.; Appleyard, W. J.; Newman, C. G. H.

1970-01-01

A trial was carried out on acidotic infants recovering from neonatal asphyxia, on the relative effects of intragastric and intravenous sodium bicarbonate on acid/base balance. Intragastric bicarbonate caused an increased rate of correction of metabolic acidosis within 30 minutes of administration. However, the Pco2 remained higher in these patients than in the controls, so that the effect of the bicarbonate on rate of pH correction was negligible. The rise in Pco2 occurred despite apparently normal respiratory function. A similar limitation of pH rise by a sustained rise in Pco2 was evident in the intravenously treated patients. Treatment of metabolic acidosis in neonates with sodium bicarbonate may not produce the desired correction of pH. PMID:5427844

Nondiabetic ketoacidosis in a pregnant woman due to acute starvation with concomitant influenza A (H1N1) and respiratory failure.

PubMed

Skalley, G; Rodríguez-Villar, S

2018-02-28

Threatening refractory metabolic acidosis due to short-term starvation nondiabetic ketoacidosis is rarely reported. Severe ketoacidosis due to starvation itself is a rare occurrence, and more so in pregnancy with a concomitant stressful clinical situation. This case report presents a nondiabetic woman admitted in intensive care for respiratory failure type 1 during the third trimester of pregnancy with a severe metabolic acidosis refractory to medical treatment. We diagnosed the patient with acute starvation ketoacidosis based on her history and the absence of other causes of high anion gap metabolic acidosis after doing a rigorous analysis of her acid-base disorder. Crown Copyright © 2018. Publicado por Elsevier España, S.L.U. All rights reserved.

Total intravenous anesthesia with propofol and remifentanil in a patient with MELAS syndrome -A case report-

PubMed Central

Park, Jin Suk; Kang, Hyun; Cha, Su Man; Park, Jung Won; Jung, Yong Hun; Woo, Young-Cheol

2010-01-01

A 23-year-old woman with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) underwent a laparoscopy-assisted appendectomy. MELAS syndrome is a multisystemic disease caused by mitochondrial dysfunction. General anesthesia has several potential hazards to patients with MELAS syndrome, such as malignant hyperthermia, hypothermia, and metabolic acidosis. In this case, anesthesia was performed with propofol, remifentanil TCI, and atracurium without any surgical or anesthetic complications. We discuss the anesthetic effects of MELAS syndrome. PMID:20508802

Total intravenous anesthesia with propofol and remifentanil in a patient with MELAS syndrome -A case report-.

PubMed

Park, Jin Suk; Baek, Chong Wha; Kang, Hyun; Cha, Su Man; Park, Jung Won; Jung, Yong Hun; Woo, Young-Cheol

2010-04-01

A 23-year-old woman with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) underwent a laparoscopy-assisted appendectomy. MELAS syndrome is a multisystemic disease caused by mitochondrial dysfunction. General anesthesia has several potential hazards to patients with MELAS syndrome, such as malignant hyperthermia, hypothermia, and metabolic acidosis. In this case, anesthesia was performed with propofol, remifentanil TCI, and atracurium without any surgical or anesthetic complications. We discuss the anesthetic effects of MELAS syndrome.

Lifetime exercise intolerance with lactic acidosis as key manifestation of novel compound heterozygous ACAD9 mutations causing complex I deficiency.

PubMed

Schrank, Bertold; Schoser, Benedikt; Klopstock, Thomas; Schneiderat, Peter; Horvath, Rita; Abicht, Angela; Holinski-Feder, Elke; Augustis, Sarunas

2017-05-01

We report a 36-year-old female having lifetime exercise intolerance and lactic acidosis with nausea associated with novel compound heterozygous Acyl-CoA dehydrogenase 9 gene (ACAD9) mutations (p.Ala390Thr and p.Arg518Cys). ACAD9 is an assembly factor for the mitochondrial respiratory chain complex I. ACAD9 mutations are recognized as frequent causes of complex I deficiency. Our patient presented with exercise intolerance, rapid fatigue, and nausea since early childhood. Mild physical workload provoked the occurrence of nausea and vomiting repeatedly. Her neurological examination, laboratory findings and muscle biopsy demonstrated no abnormalities. A bicycle spiroergometry provoked significant lactic acidosis during and following exercise pointing towards a mitochondrial disorder. Subsequently, the analysis of respiratory chain enzyme activities in muscle revealed severe isolated complex I deficiency. Candidate gene sequencing revealed two novel heterozygous ACAD9 mutations. This patient report expands the mutational and phenotypic spectrum of diseases associated with mutations in ACAD9. Copyright © 2017 Elsevier B.V. All rights reserved.

Loss of Acid Sensing Ion Channel-1a and Bicarbonate Administration Attenuate the Severity of Traumatic Brain Injury

PubMed Central

Yin, Terry; Lindley, Timothy E.; Albert, Gregory W.; Ahmed, Raheel; Schmeiser, Peter B.; Grady, M. Sean; Howard, Matthew A.; Welsh, Michael J.

2013-01-01

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in people of all ages. Following the acute mechanical insult, TBI evolves over the ensuing minutes and days. Understanding the secondary factors that contribute to TBI might suggest therapeutic strategies to reduce the long-term consequences of brain trauma. To assess secondary factors that contribute to TBI, we studied a lateral fluid percussion injury (FPI) model in mice. Following FPI, the brain cortex became acidic, consistent with data from humans following brain trauma. Administering HCO3 − after FPI prevented the acidosis and reduced the extent of neurodegeneration. Because acidosis can activate acid sensing ion channels (ASICs), we also studied ASIC1a−/− mice and found reduced neurodegeneration after FPI. Both HCO3 − administration and loss of ASIC1a also reduced functional deficits caused by FPI. These results suggest that FPI induces cerebral acidosis that activates ASIC channels and contributes to secondary injury in TBI. They also suggest a therapeutic strategy to attenuate the adverse consequences of TBI. PMID:23991103

Nutritional Biochemistry

NASA Technical Reports Server (NTRS)

Smith, Scott M.

2010-01-01

This slide presentation reviews some of the effects that space flight has on humans nutritional biochemistry. Particular attention is devoted to the study of protein breakdown, inflammation, hypercatabolism, omega 3 fatty acids, vitamin D, calcium, urine, folate and nutrient stability of certain vitamins, the fluid shift and renal stone risk, acidosis, iron/hematology, and the effects on bone of dietary protein, potassium. inflammation, and omega-3 fatty acids

Acidosis Differentially Modulates Inactivation in NaV1.2, NaV1.4, and NaV1.5 Channels

PubMed Central

Vilin, Yury Y.; Peters, Colin H.; Ruben, Peter C.

2012-01-01

NaV channels play a crucial role in neuronal and muscle excitability. Using whole-cell recordings we studied effects of low extracellular pH on the biophysical properties of NaV1.2, NaV1.4, and NaV1.5, expressed in cultured mammalian cells. Low pH produced different effects on different channel subtypes. Whereas NaV1.4 exhibited very low sensitivity to acidosis, primarily limited to partial block of macroscopic currents, the effects of low pH on gating in NaV1.2 and NaV1.5 were profound. In NaV1.2 low pH reduced apparent valence of steady-state fast inactivation, shifted the τ(V) to depolarizing potentials and decreased channels availability during onset to slow and use-dependent inactivation (UDI). In contrast, low pH delayed open-state inactivation in NaV1.5, right-shifted the voltage-dependence of window current, and increased channel availability during onset to slow and UDI. These results suggest that protons affect channel availability in an isoform-specific manner. A computer model incorporating these results demonstrates their effects on membrane excitability. PMID:22701426

[Acid-base equilibrium and the brain].

PubMed

Rabary, O; Boussofara, M; Grimaud, D

1994-01-01

In physiological conditions, the regulation of acid-base balance in brain maintains a noteworthy stability of cerebral pH. During systemic metabolic acid-base imbalances cerebral pH is well controlled as the blood/brain barrier is slowly and poorly permeable to electrolytes (HCO3- and H+). Cerebral pH is regulated by a modulation of the respiratory drive, triggered by the early alterations of interstitial fluid pH, close to medullary chemoreceptors. As blood/brain barrier is highly permeable to Co2, CSF pH is corrected in a few hours, even in case of severe metabolic acidosis and alkalosis. Conversely, during ventilatory acidosis and alkalosis the cerebral pH varies in the same direction and in the same range than blood pH. Therefore, the brain is better protected against metabolic than ventilatory acid-base imbalances. Ventilatory acidosis and alkalosis are able to impair cerebral blood flow and brain activity through interstitial pH alterations. During respiratory acidosis, [HCO3-] increases in extracellular fluids to control cerebral pH by two main ways: a carbonic anhydrase activation at the blood/brain and blood/CSF barriers level and an increase in chloride shift in glial cells (HCO3- exchanged for Cl-). During respiratory alkalosis, [HCO3-] decreases in extracellular fluids by the opposite changes in HCO3- transport and by an increase in lactic acid synthesis by cerebral cells. The treatment of metabolic acidosis with bicarbonates may induce a cerebral acidosis and worsen a cerebral oedema during ketoacidosis. Moderate hypocapnia carried out to treat intracranial hypertension is mainly effective when cerebral blood flow is high and vascular CO2 reactivity maintained. Hypocapnia may restore an altered cerebral blood flow autoregulation. Instrumental hypocapnia requires a control of cerebral perfusion pressure and cerebral arteriovenous difference for oxygen, to select patients for whom this kind of treatment may be of benefit, to choose the optimal level of hypocapnia and to avoid any deleterious effect. If hypocapnia is maintained over several days, an adaptation of CSF pH may limit the therapeutic effect on the cerebral blood flow and the intracranial pressure.

Metformin is not associated with lactic acidosis in patients with diabetes undergoing coronary artery bypass graft surgery: a case control study.

PubMed

Nazer, Rakan I; Alburikan, Khalid A

2017-05-30

Metformin associated lactic acidosis (MALA) is a rare but lethal complication. There is no consensus regarding when to stop and resume metformin in patients who undergo coronary artery bypass grafting (CABG). This study aimed to determine if uninterrupted metformin administration in patients with diabetes undergoing CABG increases the risk of lactic acidosis. Over a span of 12 months (2015-2016), 127 patients with type 2 diabetes underwent isolated CABG. Of those, 41 patients (32%) continued taking metformin and 86 patients (68%) took other antidiabetic agents. Patients taking metformin took the drug until the day of surgery and resumed taking it 3 h after extubation. There were no differences in clinical outcomes or complications between groups. Serial measurement of cardiac, liver, and kidney biomarkers were similar between groups. The mean peak lactic acid level was significantly higher in the non-metformin users (5.4 ± 2.6 vs. 7.4 ± 4.1 mmol/l; P = 0.001). Multivariable logistic regression analysis identified the need for vasopressor administration as an independent predictor of lactic acidosis (odds ratio: 7.3, 95% confidence interval: 2.5-20.6; P < 0.001). In the absence of risk factors associated with persistent lactic acidosis, such as shock or acute kidney or liver injury, continued peri-operative metformin administration was not associated with the occurrence of lactic acidosis in patients undergoing CABG. Elevated lactic acid levels seem to be directly related to tissue anoxia caused by escalating vasopressor support after surgery.

EARS2 mutations cause fatal neonatal lactic acidosis, recurrent hypoglycemia and agenesis of corpus callosum.

PubMed

Danhauser, Katharina; Haack, Tobias B; Alhaddad, Bader; Melcher, Marlen; Seibt, Annette; Strom, Tim M; Meitinger, Thomas; Klee, Dirk; Mayatepek, Ertan; Prokisch, Holger; Distelmaier, Felix

2016-06-01

Mitochondrial aminoacyl tRNA synthetases are essential for organelle protein synthesis. Genetic defects affecting the function of these enzymes may cause pediatric mitochondrial disease. Here, we report on a child with fatal neonatal lactic acidosis and recurrent hypoglycemia caused by mutations in EARS2, encoding mitochondrial glutamyl-tRNA synthetase 2. Brain ultrasound revealed agenesis of corpus callosum. Studies on patient-derived skin fibroblasts showed severely decreased EARS2 protein levels, elevated reactive oxygen species (ROS) production, and altered mitochondrial morphology. Our report further illustrates the clinical spectrum of the severe neonatal-onset form of EARS2 mutations. Moreover, in this case the live-cell parameters appeared to be more sensitive to mitochondrial dysfunction compared to standard diagnostics, which indicates the potential relevance of fibroblast studies in children with mitochondrial diseases.

Profound neonatal hypoglycemia and lactic acidosis caused by pyridoxine-dependent epilepsy.

PubMed

Mercimek-Mahmutoglu, Saadet; Horvath, Gabriella A; Coulter-Mackie, Marion; Nelson, Tanya; Waters, Paula J; Sargent, Michael; Struys, Eduard; Jakobs, Cornelis; Stockler-Ipsiroglu, Sylvia; Connolly, Mary B

2012-05-01

Pyridoxine-dependent epilepsy (PDE) was first described in 1954. The ALDH7A1 gene mutations resulting in α-aminoadipic semialdehyde dehydrogenase deficiency as a cause of PDE was identified only in 2005. Neonatal epileptic encephalopathy is the presenting feature in >50% of patients with classic PDE. We report the case of a 13-month-old girl with profound neonatal hypoglycemia (0.6 mmol/L; reference range >2.4), lactic acidosis (11 mmol/L; reference range <2), and bilateral symmetrical temporal lobe hemorrhages and thalamic changes on cranial MRI. She developed multifocal and myoclonic seizures refractory to multiple antiepileptic drugs that responded to pyridoxine. The diagnosis of α-aminoadipic semialdehyde dehydrogenase deficiency was confirmed based on the elevated urinary α-aminoadipic semialdehyde excretion, compound heterozygosity for a known splice mutation c.834G>A (p.Val278Val), and a novel putative pathogenic missense mutation c.1192G>C (p.Gly398Arg) in the ALDH7A1 gene. She has been seizure-free since 1.5 months of age on treatment with pyridoxine alone. She has motor delay and central hypotonia but normal language and social development at the age of 13 months. This case is the first description of a patient with PDE due to mutations in the ALDH7A1 gene who presented with profound neonatal hypoglycemia and lactic acidosis masquerading as a neonatal-onset gluconeogenesis defect. PDE should be included in the differential diagnosis of hypoglycemia and lactic acidosis in addition to medically refractory neonatal seizures.

Cerebral fat embolism syndrome causing brain death after long-bone fractures and acetazolamide therapy.

PubMed

Walshe, Criona M; Cooper, James D; Kossmann, Thomas; Hayes, Ivan; Iles, Linda

2007-06-01

A 19-year-old woman with multiple fractures and mild brain injury developed severe cerebral fat embolism syndrome after "damage control" orthopaedic surgery. Acetazolamide therapy to manage ocular trauma, in association with hyperchloraemia, caused a profound metabolic acidosis with appropriate compensatory hypocapnia. During ventilator weaning, unexpected brainstem coning followed increased sedation and brief normalisation of arterial carbon dioxide concentration. Autopsy found severe cerebral fat embolism and brain oedema. In patients with multiple trauma, cerebral fat embolism syndrome is difficult to diagnose, and may be more common after delayed fixation of long-bone fractures. Acetazolamide should be used with caution, as sudden restoration of normocapnia during compensated metabolic acidosis in patients with raised intracranial pressure may precipitate coning.

Extracellular Spermine Exacerbates Ischemic Neuronal Injury through Sensitization of ASIC1a Channels to Extracellular Acidosis

PubMed Central

Duan, Bo; Wang, Yi-Zhi; Yang, Tao; Chu, Xiang-Ping; Yu, Ye; Huang, Yu; Cao, Hui; Hansen, Jillian; Simon, Roger P.; Zhu, Michael X.; Xiong, Zhi-Gang; Xu, Tian-Le

2011-01-01

Ischemic brain injury is a major problem associated with stroke. It has been increasingly recognized that acid-sensing ion channels (ASICs) contribute significantly to ischemic neuronal damage, but the underlying mechanism has remained elusive. Here, we show that extracellular spermine, one of the endogenous polyamines, exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis. Pharmacological blockade of ASIC1a or deletion of the ASIC1 gene greatly reduces the enhancing effect of spermine in ischemic neuronal damage both in cultures of dissociated neurons and in a mouse model of focal ischemia. Mechanistically, spermine profoundly reduces desensitization of ASIC1a by slowing down desensitization in the open state, shifting steady-state desensitization to more acidic pH, and accelerating recovery between repeated periods of acid stimulation. Spermine-mediated potentiation of ASIC1a activity is occluded by PcTX1 (psalmotoxin 1), a specific ASIC1a inhibitor binding to its extracellular domain. Functionally, the enhanced channel activity is accompanied by increased acid-induced neuronal membrane depolarization and cytoplasmic Ca2+ overload, which may partially explain the exacerbated neuronal damage caused by spermine. More importantly, blocking endogenous spermine synthesis significantly attenuates ischemic brain injury mediated by ASIC1a but not that by NMDA receptors. Thus, extracellular spermine contributes significantly to ischemic neuronal injury through enhancing ASIC1a activity. Our data suggest new neuroprotective strategies for stroke patients via inhibition of polyamine synthesis and subsequent spermine–ASIC interaction. PMID:21307247

Ruminant Nutrition Symposium: Productivity, digestion, and health responses to hindgut acidosis in ruminants.

PubMed

Gressley, T F; Hall, M B; Armentano, L E

2011-04-01

Microbial fermentation of carbohydrates in the hindgut of dairy cattle is responsible for 5 to 10% of total-tract carbohydrate digestion. When dietary, animal, or environmental factors contribute to abnormal, excessive flow of fermentable carbohydrates from the small intestine, hindgut acidosis can occur. Hindgut acidosis is characterized by increased rates of production of short-chain fatty acids including lactic acid, decreased digesta pH, and damage to gut epithelium as evidenced by the appearance of mucin casts in feces. Hindgut acidosis is more likely to occur in high-producing animals fed diets with relatively greater proportions of grains and lesser proportions of forage. In these animals, ruminal acidosis and poor selective retention of fermentable carbohydrates by the rumen will increase carbohydrate flow to the hindgut. In more severe situations, hindgut acidosis is characterized by an inflammatory response; the resulting breach of the barrier between animal and digesta may contribute to laminitis and other disorders. In a research setting, effects of increased hindgut fermentation have been evaluated using pulse-dose or continuous abomasal infusions of varying amounts of fermentable carbohydrates. Continuous small-dose abomasal infusions of 1 kg/d of pectin or fructans into lactating cows resulted in decreased diet digestibility and decreased milk fat percentage without affecting fecal pH or VFA concentrations. The decreased diet digestibility likely resulted from increased bulk in the digestive tract or from increased digesta passage rate, reducing exposure of the digesta to intestinal enzymes and epithelial absorptive surfaces. The same mechanism is proposed to explain the decreased milk fat percentage because only milk concentrations of long-chain fatty acids were decreased. Pulse-dose abomasal fructan infusions (1 g/kg of BW) into steers resulted in watery feces, decreased fecal pH, and increased fecal VFA concentrations, without causing an inflammatory response. Daily 12-h abomasal infusions of a large dose of starch (~4 kg/d) have also induced hindgut acidosis as indicated by decreased fecal pH and watery feces. On the farm, watery or foamy feces or presence of mucin casts in feces may indicate hindgut acidosis. In summary, hindgut acidosis occurs because of relatively high rates of large intestinal fermentation, likely due to digestive dysfunction in other parts of the gut. A better understanding of the relationship of this disorder to other animal health disorders is needed.

Metformin-induced lactic acidosis: a case series.

PubMed

Silvestre, Joana; Carvalho, Susana; Mendes, Vitor; Coelho, Luis; Tapadinhas, Camila; Ferreira, Pedro; Povoa, Pedro; Ceia, Fatima

2007-10-31

Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. It is therefore being increasingly used in higher doses. The major concern of many physicians is a possible risk of lactic acidosis. The reported frequency of metformin related lactic acidosis is 0.05 per 1000 patient-years; some authors advocate that this rate is equal in those patients not taking metformin. We present two case reports of metformin-associated lactic acidosis. The first case is a 77 year old female with a past medical history of hypertension and type 2 diabetes mellitus who had recently been prescribed metformin (3 g/day), perindopril and acetylsalicylic acid. She was admitted to the emergency department two weeks later with abdominal pain and psychomotor agitation. Physical examination revealed only signs of poor perfusion. Laboratory evaluation revealed hyperkalemia, elevated creatinine and blood urea nitrogen and mild leukocytosis. Arterial blood gases showed severe lactic acidemia. She was admitted to the intensive care unit. Vasopressor and ventilatory support was initiated and continuous venovenous hemodiafiltration was instituted. Twenty-four hours later, full clinical recovery was observed, with return to a normal serum lactate level. The patient was discharged from the intensive care unit on the sixth day. The second patient is a 69 year old male with a past medical history of hypertension, type 2 diabetes mellitus and ischemic heart disease who was on metformin (4 g/day), glycazide, acetylsalicylic acid and isosorbide dinitrate. He was admitted to the emergency department in shock with extreme bradycardia. Initial evaluation revealed severe lactic acidosis and elevated creatinine and urea. The patient was admitted to the Intensive Care Unit and commenced on continuous venovenous hemodiafiltration in addition to other supportive measures. A progressive recovery was observed and he was discharged from the intensive care unit on the seventh day. We present two case reports of severe lactic acidosis most probably associated with high doses of metformin in patients with no known contraindications for metformin prescription. In both patients no other condition was identified to cause such severe lactic acidosis. Although controversial, lactic acidosis should be considered in patients taking metformin.

High anion gap metabolic acidosis induced by cumulation of ketones, L- and D-lactate, 5-oxoproline and acute renal failure.

PubMed

Heireman, Laura; Mahieu, Boris; Helbert, Mark; Uyttenbroeck, Wim; Stroobants, Jan; Piqueur, Marian

2017-07-27

Frequent causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis and impaired renal function. In this case report, a HAGMA caused by ketones, L- and D-lactate, acute renal failure as well as 5-oxoproline is discussed. A 69-year-old woman was admitted to the emergency department with lowered consciousness, hyperventilation, diarrhoea and vomiting. The patient had suffered uncontrolled type 2 diabetes mellitus, underwent gastric bypass surgery in the past and was chronically treated with high doses of paracetamol and fosfomycin. Urosepsis was diagnosed, whilst laboratory analysis of serum bicarbonate concentration and calculation of the anion gap indicated a  HAGMA. L-lactate, D-lactate, β-hydroxybutyric acid, acetone and 5-oxoproline serum levels were markedly elevated and renal function was impaired. We concluded that this case of HAGMA was induced by a variety of underlying conditions: sepsis, hyperglycaemia, prior gastric bypass surgery, decreased renal perfusion and paracetamol intake. Risk factors for 5-oxoproline intoxication present in this case are female gender, sepsis, impaired renal function and uncontrolled type 2 diabetes mellitus. Furthermore, chronic antibiotic treatment with fosfomycin might have played a role in the increased production of 5-oxoproline. Paracetamol-induced 5-oxoproline intoxication should be considered as a cause of HAGMA in patients with female gender, sepsis, impaired renal function or uncontrolled type 2 diabetes mellitus, even when other more obvious causes of HAGMA such as lactate, ketones or renal failure can be identified.

Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog.

PubMed

López, Ignacio; Aguilera-Tejero, Escolástico; Estepa, José Carlos; Rodríguez, Mariano; Felsenfeld, Arnold J

2004-05-01

Recently, we showed that both acute metabolic acidosis and respiratory acidosis stimulate parathyroid hormone (PTH) secretion in the dog. To evaluate the specific effect of acidosis, ionized calcium (iCa) was clamped at a normal value. Because iCa values normally increase during acute acidosis, we now have studied the PTH response to acute metabolic and respiratory acidosis in dogs in which the iCa concentration was allowed to increase (nonclamped) compared with dogs with a normal iCa concentration (clamped). Five groups of dogs were studied: control, metabolic (clamped and nonclamped), and respiratory (clamped and nonclamped) acidosis. Metabolic (HCl infusion) and respiratory (hypoventilation) acidosis was progressively induced during 60 min. In the two clamped groups, iCa was maintained at a normal value with an EDTA infusion. Both metabolic and respiratory acidosis increased (P < 0.05) iCa values in nonclamped groups. In metabolic acidosis, the increase in iCa was progressive and greater (P < 0.05) than in respiratory acidosis, in which iCa increased by 0.04 mM and then remained constant despite further pH reductions. The increase in PTH values was greater (P < 0.05) in clamped than in nonclamped groups (metabolic and respiratory acidosis). In the nonclamped metabolic acidosis group, PTH values first increased and then decreased from peak values when iCa increased by > 0.1 mM. In the nonclamped respiratory acidosis group, PTH values exceeded (P < 0.05) baseline values only after iCa values stopped increasing at a pH of 7.30. For the same increase in iCa in the nonclamped groups, PTH values increased more in metabolic acidosis. In conclusion, 1) both metabolic acidosis and respiratory acidosis stimulate PTH secretion; 2) the physiological increase in the iCa concentration during the induction of metabolic and respiratory acidosis reduces the magnitude of the PTH increase; 3) in metabolic acidosis, the increase in the iCa concentration can be of sufficient magnitude to reverse the increase in PTH values; and 4) for the same degree of acidosis-induced hypercalcemia, the increase in PTH values is greater in metabolic than in respiratory acidosis.

Delayed posthypoxic demyelination. Association with arylsulfatase A deficiency and lactic acidosis on proton MR spectroscopy.

PubMed

Gottfried, J A; Mayer, S A; Shungu, D C; Chang, Y; Duyn, J H

1997-11-01

Delayed demyelination is a rare and poorly understood complication of hypoxic brain injury. A previous case report has suggested an association with mild-to-moderate deficiency of arylsulfatase A. We describe a 36-year-old man who recovered completely from an episode of hypoxia related to drug overdose, and 2 weeks later progressed from a confusional state to deep coma. MRI showed diffuse white matter signal changes, and brain biopsy demonstrated a noninflammatory demyelinating process. Proton magnetic resonance spectroscopy revealed elevated choline and lactate and reduced N-acetyl aspartate signal in the affected white matter, consistent with demyelination and a shift to anaerobic metabolism. Arylsulfatase A activity from peripheral leukocytes was approximately 50% of normal, consistent with a "pseudodeficiency" phenotype. These findings confirm the hypothesis that relative arylsulfatase A deficiency predisposes susceptible individuals to delayed posthypoxic leukoencephalopathy and implicates lactic acidosis in the pathogenesis of this disorder.

Refeeding syndrome as an unusual cause of anion gap metabolic acidosis.

PubMed

Singla, Manish; Perry, Alexandra; Lavery, Eric

2012-11-01

Refeeding syndrome is characterized by hypophosphatemia in the setting of malnutrition. It is commonly seen in patients with anorexia, alcoholism, or malignancy, and it is often a missed diagnosis. Because of the potential morbidity associated with missing the diagnosis of refeeding syndrome, it is important to monitor for this disease in any malnourished patient. We present a case of a 49-year-old male with chronic alcohol abuse who presented for alcohol detoxification and was found to have low phosphate, potassium, and magnesium on presentation, in addition to an elevated anion gap of unclear etiology. After extensive workup to evaluate the cause of his elevated anion gap and worsening of his electrolyte abnormalities despite replenishment, it was felt his symptoms were a result of refeeding syndrome. After oral intake was held and aggressive electrolyte replenishment was performed for 24 hours, the patient's anion gap closed and his electrolyte levels stabilized. This case demonstrates a unique presentation of refeeding syndrome given the patient's profound metabolic acidosis that provided a clue toward his eventual diagnosis. The standard workup for an anion gap metabolic acidosis was negative, and it was not until his refeeding syndrome had been treated that the anion gap closed.

The profound impact of combined severe acidosis and malperfusion on operative mortality in the surgical treatment of type A aortic dissection.

PubMed

Lawton, Jennifer S; Moon, Marc R; Liu, Jingxia; Koerner, Danielle J; Kulshrestha, Kevin; Damiano, Ralph J; Maniar, Hersh; Itoh, Akinobu; Balsara, Keki R; Masood, Faraz M; Melby, Spencer J; Pasque, Michael K

2018-03-01

Surgery for type A aortic dissection is associated with a high operative mortality, and a variety of predictive risk factors have been reported. We hypothesized that a combination of risk factors associated with organ malperfusion and severe acidosis that are not currently documented in databases would be associated with a level of extreme operative risk that would warrant the consideration of treatment paradigms other than immediate ascending aortic surgery. Charts of patients undergoing repair of acute type A aortic dissection between January 1, 1996, and May 1, 2016, were queried for preoperative malperfusion, preoperative base deficit, pH, bicarbonate, cardiopulmonary resuscitation, severe aortic insufficiency, redo status, and preoperative intubation. Multivariable logistic analyses were considered to evaluate interested variables and operative mortality. Between January 1, 1996, and May 1, 2016, 282 patients underwent surgical repair of type A aortic dissection. A total of 66 patients had a calculated base deficit -5 or greater. Eleven of 12 patients (92%) with severe acidosis (base deficit ≥-10) with malperfusion had operative mortality. No patient with severe acidosis with abdominal malperfusion survived. Multivariable analyses identified base deficit, intubation, congestive heart failure, dyslipidemia/statin use, and renal failure as predictors of operative death. The most significant predictor was base deficit -10 or greater (odds ratio, 9.602; 95% confidence interval, 2.649-34.799). The combination of severe acidosis (base deficit ≥-10) with abdominal malperfusion was uniformly fatal. Further research is needed to determine whether the identification of extreme risk warrants consideration of alternate treatment options to address the cause of severe acidosis before ascending aortic procedures. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

A Practical Approach to Vitamin D Deficiency and Rickets.

PubMed

Allgrove, Jeremy; Shaw, Nick J

2015-01-01

Rickets is a condition in which there is failure of the normal mineralisation (osteomalacia) of growing bone. Whilst osteomalacia may be present in adults, rickets cannot occur. It is generally caused by a lack of mineral supply, which can either occur as a result of the deficiency of calcium (calciopaenic rickets, now known as parathyroid hormone-dependent rickets) or of phosphate (phosphopaenic rickets, now called FGF23-dependent rickets). Renal disorders may also interfere with the process of mineralisation and cause rickets. Only parathyroid hormone-dependent rickets and distal renal tubular disorders will be discussed in this chapter. The most common cause of rickets is still vitamin D deficiency, which is also responsible for other problems. Disorders of vitamin D metabolism or responsiveness may also cause similar issues. Distal renal tubular acidosis may also be caused by a variety of metabolic errors similar to those of osteoclasts. One form of distal renal tubular acidosis also causes a type of osteopetrosis. This chapter describes these conditions in detail and sets out a logical approach for treatment. © 2015 S. Karger AG, Basel.

Individual animal variability in ruminal bacterial communities and ruminal acidosis in primiparous Holstein cows during the periparturient period.

PubMed

Mohammed, R; Stevenson, D M; Weimer, P J; Penner, G B; Beauchemin, K A

2012-11-01

The purpose of this study was to investigate variability among individual cows in their severity of ruminal acidosis (RA) pre- and postpartum, and determine whether this variability was related to differences in their ruminal bacterial community composition (BCC). Variability in the severity of RA among individual cows was characterized based on ruminal fermentation variables. Effects of prepartum dietary treatment on the severity of RA were also examined. Fourteen Holstein heifers paired by expected calving date and BCS were allotted to 1 of 2 prepartum dietary treatments: low-concentrate or high-concentrate diets. All cows received the same lactation diet postpartum. Microbial DNA extracted from 58 ruminal digesta samples in total collected prepartum (d -50, -31, and -14; 27 samples) and postpartum (d +14 and +52; 31 samples) and amplified by PCR were subjected to automated ribosomal intergenic spacer analysis. Changes in ruminal variables over time [pH, volatile fatty acids (VFA), and acidosis indicators, including duration and area under the rumen pH curve below 5.8, 5.5, and 5.2, measured on d -54, -35, -14, -3, +3, +17, +37, and +58] were analyzed using principal components analysis. Based on the shift (defined as the distance of the mean loadings) between the prepartum and postpartum period for each cow, the 14 cows were classified into 3 groups: least acidotic (n=5), most acidotic (n=5), and intermediate (n=4). Cows in the most acidotic group had greater severity of RA (measured as duration of total RA, mild RA, moderate RA, and acute RA; area under the pH curve for total RA, mild RA, and moderate RA) postpartum than prepartum, and this difference between periods was greater than for the least acidotic cows. Similarly, the RA index (total area of pH <5.8 normalized to intake) showed an interaction between severity of RA and period. The variation in the severity of RA was independent of intake, total VFA concentration, and individual VFA proportions. Production variables (milk yield, fat percentage, fat yield, fat-corrected milk, and efficiency of milk production) were not influenced by the severity of RA. Ruminal BCC was not influenced by dietary treatment or period. However, some cows experienced greater shift in BCC than other cows across the periods. Based on the magnitude of the shift in BCC (distance between mean ordination values across the periods for each cow), cows were grouped into 3 BCC profile categories: stable (5 cows with lesser shift), unstable (5 cows with greater shift), and intermediate (4 cows with average shift). Cows demonstrating a greater shift in BCC were not necessarily those in the most acidotic group and vice versa. The shift in ruminal fermentation variables (principal components analysis rankings) and the shift in BCC (automated ribosomal intergenic spacer analysis rankings) between pre- and postpartum were not related (n=14; R(2)=0.00). It was concluded that not all cows are equally susceptible to RA and postpartum shifts in BCC appear to be independent of the differences in the severity of RA postpartum. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Pulmonary hypertension and right heart failure due to severe hypernatremic dehydration.

PubMed

Chiwane, Saurabh; Ahmed, Tageldin M; Bauerfeld, Christian P; Chauhan, Monika

2017-07-01

Neonates are at risk of developing hypernatremic dehydration and its associated complications, such as stroke, dural sinus thrombosis and renal vein thrombosis. Pulmonary hypertension has not been described as a complication of hypernatremia. We report a case of a seven-day-old neonate with severe hypernatremic dehydration who went on to develop pulmonary hypertension and right heart failure needing extracorporeal membrane oxygenation (ECMO). Normal or high anion gap metabolic acidosis commonly accompanies hypernatremic dehydration. The presence of acidosis and/or hypoxia can delay the normal drop in pulmonary vascular resistance (PVR) after birth, causing pulmonary hypertension and right ventricular failure. A high index of suspicion is paramount to diagnose pulmonary hypertension and aggressive correction of the acidosis and hypoxia is needed. In the presence of severe right ventricular failure, ECMO can be used as a bridge to recovery while underlying metabolic derangements are being corrected.

A patient with Graves' disease who survived despite developing thyroid storm and lactic acidosis.

PubMed

Yoshino, Tetsuhiro; Kawano, Daisuke; Azuhata, Takeo; Kuwana, Tsukasa; Kogawa, Rikimaru; Sakurai, Atsushi; Tanjoh, Katsuhisa; Yanagawa, Tatsuo

2010-11-01

A 56-year-old woman with Graves' disease presented with the complaints of diarrhea and palpitations. Physical examination and laboratory data revealed hypothermia and signs of mild hyperthyroidism, heart failure, hepatic dysfunction with jaundice, hypoglycemia, and lactic acidosis. The patient was diagnosed as having developed the complication of thyroid storm in the absence of marked elevation of the thyroid hormone levels, because of the potential hepatic and cardiac dysfunctions caused by heavy alcohol drinking. A year later, after successful treatment, the patient remains well without any clinical evidence of heart failure or hepatic dysfunction. Thyroid storm associated with lactic acidosis and hypothermia is a serious condition and has rarely been reported. Prompt treatment is essential even if the serum thyroid hormone levels are not markedly elevated. We present a report about this patient, as her life could eventually be saved.

Pyroglutamic acidosis in association with therapeutic paracetamol use.

PubMed

Hunter, Robert W; Lawson, Cate; Galitsiou, Evangelia; Gifford, Fiona; Neary, John J

2016-12-01

Long-term use of paracetamol (at therapeutic doses) can cause the accumulation of endogenous organic pyroglutamate, resulting in metabolic acidosis with an elevated anion gap. This occurs in the presence of malnutrition, infection, antibiotic use, renal failure and pregnancy. Given the prevalence of these risk factors, this condition is thought to be relatively common in a hospitalised population but is probably significantly underdiagnosed. Prompt recognition is essential because the condition is entirely reversible if the causative agents are withdrawn.Here we describe five cases of pyroglutamic acidosis that we have encountered in a tertiary referral hospital. Together they illustrate the common clinical risk factors and the excellent prognosis, once a diagnosis is made. We describe how a rudimentary acid-base analysis (calculation of the anion gap) usually leads to the diagnosis but how a more nuanced approach may be required in the presence of mixed acid-base disorders. © Royal College of Physicians 2016. All rights reserved.

[A young child with respiratory acidosis and hypoxia from mechanical ventilation with equipment made for adults].

PubMed

Joor, Fleur; Markhorst, Dick G; Kneyber, Martin C J; van Heerde, Marc

2011-01-01

During mechanical ventilation of young children, problems may arise due to the additional dead space of the ventilation circuit. This may lead to respiratory acidosis and even hypoxia in the child. A 3-month-old boy suffered from frequent apnoea. He was mechanically ventilated for this. Shortly after its initiation, he developed severe respiratory acidosis, hypoxemia and circulatory insufficiency. This was due to a large additional dead space caused by the use of equipment components made for adults. After he was switched to a circuit suitable for himself, he recovered rapidly. As a rule of thumb, an additional dead space of 1.5-2 ml/kg body weight is acceptable in young children. Emergency wards for young children should have specific equipment to mechanically ventilate them, and have a protocol paying explicit attention to the dead space.

A rare cause of metabolic acidosis: ketoacidosis in a non-diabetic lactating woman

PubMed Central

Ali, Amjad; Webster, Jonathan

2017-01-01

Ketoacidosis occurring during lactation has been described infrequently. The condition is incompletely understood, but it appears to be associated with a combination of increased metabolic demands during lactation, reduction in carbohydrate intake and acute illness. We present a case of a 27-year-old woman, 8 weeks post-partum, who was exclusively breastfeeding her child whilst following a low carbohydrate diet. She developed gastroenteritis and was unable to tolerate an oral diet for several days. She presented with severe metabolic acidosis on admission with a blood 3-hydroxybutyrate of 5.4 mmol/L. She was treated with intravenous dextrose and intravenous sodium bicarbonate, and given dietary advice to increase her carbohydrate intake. She made a rapid and full recovery. We provide a summary of the common causes of ketoacidosis and compare our case with other presentations of lactation ketoacidosis. Learning points: Ketoacidosis in the lactating woman is a rare cause of raised anion gap metabolic acidosis. Low carbohydrate intake, starvation, intercurrent illness or a combination of these factors could put breastfeeding women at risk of ketoacidosis. Ketoacidosis in the lactating woman has been shown to resolve rapidly with sufficient carbohydrate intake and intravenous dextrose. Early diagnosis and prompt treatment are essential because the condition is reported to be reversible with a low chance of recurrence with appropriate dietary advice. PMID:28924478

Quantification of paracetamol and 5-oxoproline in serum by capillary electrophoresis: Implication for clinical toxicology.

PubMed

Hložek, Tomáš; Křížek, Tomáš; Tůma, Petr; Bursová, Miroslava; Coufal, Pavel; Čabala, Radomír

2017-10-25

High anion gap metabolic acidosis frequently complicates acute paracetamol overdose and is generally attributed to lactic acidosis or compromised hepatic function. However, metabolic acidosis can also be caused by organic acid 5-oxoproline (pyroglutamic acid). Paracetamol's toxic intermediate, N-acetyl-p-benzoquinoneimine irreversibly binds to glutathione and its depletion leads to subsequent disruption of the gamma glutamyl cycle and an excessive 5-oxoproline generation. This is undoubtedly an underdiagnosed condition because measurement of serum 5-oxoproline level is not readily available. A simple, cost effective, and fast capillary electrophoresis method with diode array detection (DAD) for simultaneous measurement of both paracetamol (acetaminophen) and 5-oxoproline in serum was developed and validated. This method is highly suitable for clinical toxicology laboratory diagnostic, allowing rapid quantification of acidosis inducing organic acid 5-oxoproline present in cases of paracetamol overdose. The calibration dependence of the method was proved to be linear in the range of 1.3-250μgmL -1 , with adequate accuracy (96.4-107.8%) and precision (12.3%). LOQ equaled 1.3μgmL -1 for paracetamol and 4.9μgmL -1 for 5-oxoproline. Copyright © 2017 Elsevier B.V. All rights reserved.

Determination of the acid-base status in 50 horses admitted with colic between December 1998 and May 1999.

PubMed Central

Nappert, G; Johnson, P J

2001-01-01

The purpose of the present study was to investigate the acid-base status and the concentration of organic acids in horses with colic caused by various disorders. Blood samples were collected from 50 horses with colic and from 20 controls. No intravenous fluids had been given prior to sample collection. Identified causes of colic included gastric ulceration, small intestinal volvulus, cecal intussusception, cecal rupture, colonic impaction, left dorsal colon displacement, right dorsal colon displacement, colonic volvulus, colitis, peritonitis, and uterine torsion. Thirty-seven horses recovered from treatment of colic, 8 horses were euthanized, and 5 died. Most cases were not in severe metabolic acidosis. In previous studies, most horses presented for diagnosis and treatment of colic were in metabolic acidosis and in shock. PMID:11565369

Acute esophageal necrosis caused by alcohol abuse

PubMed Central

Endo, Tetsu; Sakamoto, Juichi; Sato, Ken; Takimoto, Miyako; Shimaya, Koji; Mikami, Tatsuya; Munakata, Akihiro; Shimoyama, Tadashi; Fukuda, Shinsaku

2005-01-01

Acute esophageal necrosis (AEN) is extremely rare and the pathogenesis of this is still unknown. We report a case of AEN caused by alcohol abuse. In our case, the main pathogenesis could be accounted for low systemic perfusion caused by severe alcoholic lactic acidosis. After the healing of AEN, balloon dilatation was effective to manage the stricture. PMID:16222758

Friedrich Nietzsche (1844-1900): a classical case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome?

PubMed

Koszka, Christiane

2009-08-01

Friedrich Nietzsche was one of the most influential and profound German philosophers. After prolonged illness, he died at the age of 55 in Weimar, Germany. The interest in his medical biography has always been strong while the cause of his illness and death has remained a mystery, intriguing philosophers as well as physicians. The diagnosis of syphilis proposed in the 19th century has been controversial until today and many other diagnoses have been discussed. This paper suggests that Nietzsche suffered from mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome.

Incidence, nature, and etiology of metabolic acidosis in dogs and cats.

PubMed

Hopper, K; Epstein, S E

2012-01-01

Metabolic acidosis is an important abnormality in ill and injured dogs and cats. To describe the incidence, nature, and etiology of metabolic acidosis in dogs and cats that had arterial or venous blood gases measured for any reason at a university teaching hospital. Dogs and cats at the Veterinary Medical Teaching Hospital. Acid base parameters and electrolyte and lactate concentrations in dogs and cats measured during a 13-month period were retrospectively retrieved from a computer database. Metabolic acidosis was defined as a standardized base excess (SBE) in dogs of <-4 mmol/L and in cats <-5 mmol/L. A total of 1,805 dogs and cats were included; of these, 887 (49%) were classified as having a metabolic acidosis (753 dogs and 134 cats). Primary metabolic acidosis was the most common disorder in dogs, whereas mixed acid base disorder of metabolic acidosis and respiratory acidosis was most common in cats. Hyperchloremic metabolic acidosis was more common than a high anion gap (AG) metabolic acidosis; 25% of dogs and 34% of cats could not be classified as having either a hyperchloremic metabolic acidosis or a high AG metabolic acidosis. Metabolic acidosis was found commonly in this patient population and was associated with a wide variety of disease processes. Mixed acid base disorders occur frequently and routine categorization of metabolic acidosis based on the presence of high AG or hyperchloremia may be misleading in a large proportion of cases. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Simultaneous Hypoxia and Low Extracellular pH Suppress Overall Metabolic Rate and Protein Synthesis In Vitro.

PubMed

Sørensen, Brita Singers; Busk, Morten; Overgaard, Jens; Horsman, Michael R; Alsner, Jan

2015-01-01

The tumor microenvironment is characterized by regions of hypoxia and acidosis which are linked to poor prognosis. This occurs due to an aberrant vasculature as well as high rates of glycolysis and lactate production in tumor cells even in the presence of oxygen (the Warburg effect), which weakens the spatial linkage between hypoxia and acidosis. Five different human squamous cell carcinoma cell lines (SiHa, FaDuDD, UTSCC5, UTSCC14 and UTSCC15) were treated with hypoxia, acidosis (pH 6.3), or a combination, and gene expression analyzed using microarray. SiHa and FaDuDD were chosen for further characterization of cell energetics and protein synthesis. Total cellular ATP turnover and relative glycolytic dependency was determined by simultaneous measurements of oxygen consumption and lactate synthesis rates and total protein synthesis was determined by autoradiographic quantification of the incorporation of 35S-labelled methionine and cysteine into protein. Microarray analysis allowed differentiation between genes induced at low oxygen only at normal extracellular pH (pHe), genes induced at low oxygen at both normal and low pHe, and genes induced at low pHe independent of oxygen concentration. Several genes were found to be upregulated by acidosis independent of oxygenation. Acidosis resulted in a more wide-scale change in gene expression profiles than hypoxia including upregulation of genes involved in the translation process, for example Eukaryotic translation initiation factor 4A, isoform 2 (EIF4A2), and Ribosomal protein L37 (RPL37). Acidosis suppressed overall ATP turnover and protein synthesis by 50%. Protein synthesis, but not total ATP production, was also suppressed under hypoxic conditions. A dramatic decrease in ATP turnover (SiHa) and protein synthesis (both cell lines) was observed when hypoxia and low pHe were combined. We demonstrate here that the influence of hypoxia and acidosis causes different responses, both in gene expression and in de novo protein synthesis, depending on whether the two factors induced alone or overlapping, and as such it is important for in vivo studies to take this into account.

Simultaneous Hypoxia and Low Extracellular pH Suppress Overall Metabolic Rate and Protein Synthesis In Vitro

PubMed Central

Sørensen, Brita Singers; Busk, Morten; Overgaard, Jens; Horsman, Michael R.; Alsner, Jan

2015-01-01

Background The tumor microenvironment is characterized by regions of hypoxia and acidosis which are linked to poor prognosis. This occurs due to an aberrant vasculature as well as high rates of glycolysis and lactate production in tumor cells even in the presence of oxygen (the Warburg effect), which weakens the spatial linkage between hypoxia and acidosis. Methods Five different human squamous cell carcinoma cell lines (SiHa, FaDuDD, UTSCC5, UTSCC14 and UTSCC15) were treated with hypoxia, acidosis (pH 6.3), or a combination, and gene expression analyzed using microarray. SiHa and FaDuDD were chosen for further characterization of cell energetics and protein synthesis. Total cellular ATP turnover and relative glycolytic dependency was determined by simultaneous measurements of oxygen consumption and lactate synthesis rates and total protein synthesis was determined by autoradiographic quantification of the incorporation of 35S-labelled methionine and cysteine into protein. Results Microarray analysis allowed differentiation between genes induced at low oxygen only at normal extracellular pH (pHe), genes induced at low oxygen at both normal and low pHe, and genes induced at low pHe independent of oxygen concentration. Several genes were found to be upregulated by acidosis independent of oxygenation. Acidosis resulted in a more wide-scale change in gene expression profiles than hypoxia including upregulation of genes involved in the translation process, for example Eukaryotic translation initiation factor 4A, isoform 2 (EIF4A2), and Ribosomal protein L37 (RPL37). Acidosis suppressed overall ATP turnover and protein synthesis by 50%. Protein synthesis, but not total ATP production, was also suppressed under hypoxic conditions. A dramatic decrease in ATP turnover (SiHa) and protein synthesis (both cell lines) was observed when hypoxia and low pHe were combined. Conclusions We demonstrate here that the influence of hypoxia and acidosis causes different responses, both in gene expression and in de novo protein synthesis, depending on whether the two factors induced alone or overlapping, and as such it is important for in vivo studies to take this into account. PMID:26274822

Renal Tubular Acidosis

MedlinePlus

... other organs. Hyperkalemic RTA can be caused by urinary tract infections (UTIs) , autoimmune disorders, sickle cell disease, diabetes, kidney ... Vesicoureteral Reflux (VUR) Glomerulonephritis Kidney Diseases in Childhood Urinary Tract Infections When Your Child Has a Chronic Kidney Disease ...

Band 3 nullVIENNA , a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis.

PubMed

Kager, Leo; Bruce, Lesley J; Zeitlhofer, Petra; Flatt, Joanna F; Maia, Tabita M; Ribeiro, M Leticia; Fahrner, Bernhard; Fritsch, Gerhard; Boztug, Kaan; Haas, Oskar A

2017-03-01

We describe the second patient with anionic exchanger 1/band 3 null phenotype (band 3 null VIENNA ), which was caused by a novel nonsense mutation c.1430C>A (p.Ser477X) in exon 12 of SLC4A1. We also update on the previous band 3 null COIMBRA patient, thereby elucidating the physiological implications of total loss of AE1/band 3. Besides transfusion-dependent severe hemolytic anemia and complete distal renal tubular acidosis, dyserythropoiesis was identified in the band 3 null VIENNA patient, suggesting a role for band 3 in erythropoiesis. Moreover, we also, for the first time, report that long-term survival is possible in band 3 null patients. © 2016 Wiley Periodicals, Inc.

Disulfiram inhibition of cyanide formation after acetonitrile poisoning.

PubMed

De Paepe, Peter; Colin, Pieter; Depuydt, Pieter; Decavele, An-Sofie; De Smet, Julie; Boussery, Koen; Stove, Christophe; Benoit, Dominique; Verstraete, Alain; Van Bocxlaer, Jan; Buylaert, Walter

2016-01-01

Cyanide poisoning may be caused by acetonitrile, a common industrial organic solvent and laboratory agent. To describe the potential use of disulfiram in treating acetonitrile poisoning in a human clinical case and to further study its effect in human liver microsomes in vitro. A 30-year-old man initially presented with a cholinergic toxic syndrome following ingestion of aldicarb. Toxicological analysis revealed coingestion of ethanol. He subsequently developed severe metabolic acidosis caused by the cyanogenic compound acetonitrile which was erroneously interpreted as acetone in the chromatogram. After three treatments with hydroxocobalamin (5 g i.v.) and sodium thiosulfate (12.5 g i.v.) on days 2, 3, and 5, he had transient improvement but recurrent lactic acidosis. Treatment with disulfiram was associated on day 7 with resolution of metabolic acidosis and slowing of the decrease in acetonitrile concentration. He recovered from acetonitrile toxicity completely. The time course of acetonitrile, thiocyanate, and cyanide concentrations suggested that disulfiram inhibited cyanide formation. In vitro experiments with human liver microsomes showed the cyanide concentration was significantly lower after incubation with acetonitrile and disulfiram than acetonitrile alone (a mean 60% reduction in cyanide level). Although disulfiram was given late in the course of the poisoning it is possible that it contributed to the recovery.

Activation of central muscarinic receptors causes respiratory stimulation in conscious animals.

PubMed Central

Weinstock, M.

1981-01-01

1 Oxotremorine (10 microgram/kg) injected intravenously into conscious rabbits pretreated with atropine-methyl-nitrate (ATMN, 0.5 mg/kg) caused significant increases in respiration rate from 94 to 131 per min, and in PaO2 from 13.8 to 15.4 kPa, and a decrease in PaCO2 from 3.30 to 2.09 pKa within 15 min. Blood pH fell from 7.44 to 7.16. 2 Blood pressure increased by 11.6%, 5 min after oxotremorine injection. 3 The acidosis was shown to be due to an increase in blood lactic acid from 41 to 132 mg/100 ml. 4 Pretreatment with propranolol (5 mg/kg s.c.) prevented the lactic acidosis and fall in pH but did not alter the respiratory stimulation induced by oxotremorine. 5 It is suggested that the lactic acidosis induced by oxotremorine results from stimulation of beta-adrenoceptors in skeletal muscle by catecholamines released from the adrenal medulla and sympathetic nerves. 6 Since all the above effects of oxotremorine are antagonized by hyoscine (5 mg/kg) but not by ATMN (0.5 mg/kg), it is concluded that oxotremorine can stimulate respiration by a direct action on muscarinic receptors in the central nervous system. PMID:7296163

Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism

PubMed Central

Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Lamers, Wouter H.; Chaudhry, Farrukh A.; Verlander, Jill W.

2016-01-01

Glutamine synthetase (GS) catalyzes the recycling of NH4+ with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na+-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression. PMID:27009341

Unexplained metabolic acidosis in critically ill patients: the role of pyroglutamic acid.

PubMed

Mizock, Barry A; Belyaev, Stanislav; Mecher, Carter

2004-03-01

To determine the role of pyroglutamic acid (PGA) in the pathogenesis of unexplained metabolic acidosis in critically ill patients. Case series in the medical ICU of an urban hospital. 23 patients admitted to the medical ICU with acidemia (pH <7.35 or HC0(3) < or = 16 mEq/l) not explained by the presence of ketoacidosis, lactic acidosis, renal failure or ingestion of drugs or toxins and who had an increase in the strong ion gap (SIG) greater than 5. Plasma levels of sodium, potassium, chloride, bicarbonate, calcium (ionized), magnesium, lactate, phosphate, albumin, blood urea nitrogen, and creatinine were measured. Arterial blood gases and urine dipstick for ketones were also analyzed. Plasma was assayed for PGA using gas chromatography. The patient's history and Kardex were reviewed for evidence of acetaminophen administration. The plasma PGA level was found to be very low in all patients studied. The correlation between SIG and PGA (r) was -0.01 (95% CI: -0.42 to 0.40). PGA therefore did not account for the observed increase in the SIG. There appeared to be no obvious influence of acetaminophen intake on levels of PGA in the plasma. We were unable to confirm the importance of PGA as a cause of unexplained metabolic acidosis and increased SIG in our critically ill patients.

Cleistanthus collinus induces type I distal renal tubular acidosis and type II respiratory failure in rats.

PubMed

Maneksh, Delinda; Sidharthan, Anita; Kettimuthu, Kavithapriya; Kanthakumar, Praghalathan; Lourthuraj, Amala A; Ramachandran, Anup; Subramani, Sathya

2010-06-01

A water decoction of the poisonous shrub Cleistanthus collinus is used for suicidal purposes. The mortality rate is 28%. The clinical profile includes distal renal tubular acidosis (DRTA) and respiratory failure. The mechanism of toxicity is unclear. To demonstrate features of C. collinus toxicity in a rat model and to identify its mechanism(s) of action. Rats were anesthetized and the carotid artery was cannulated. Electrocardiogram and respiratory movements were recorded. Either aqueous extract of C. collinus or control solution was administered intraperitoneally. Serial measurements of blood gases, electrolytes and urinary pH were made. Isolated brush border and basolateral membranes from rat kidney were incubated with C. collinus extract and reduction in ATPase activity was assessed. Venous blood samples from human volunteers and rats were incubated with an acetone extract of C. collinus and plasma potassium was estimated as an assay for sodium-potassium pump activity. The mortality was 100% in tests and 17% in controls. Terminal event in test animals was respiratory arrest. Controls had metabolic acidosis, respiratory compensation acidic urine and hyperkalemia. Test animals showed respiratory acidosis, alkaline urine and low blood potassium as compared to controls. C. collinus extract inhibited ATPase activity in rat kidney. Plasma K(+) did not increase in human blood incubated with C. collinus extract. Active principles of C. collinus inhibit proton pumps in the renal brush border, resulting in type I DRTA in rats. There is no inhibition of sodium-potassium pump activity. Test animals develop respiratory acidosis, and the immediate cause of death is respiratory arrest.

D-lactic acidosis: an underrecognized complication of short bowel syndrome.

PubMed

Kowlgi, N Gurukripa; Chhabra, Lovely

2015-01-01

D-lactic acidosis or D-lactate encephalopathy is a rare condition that occurs primarily in individuals who have a history of short bowel syndrome. The unabsorbed carbohydrates act as a substrate for colonic bacteria to form D-lactic acid among other organic acids. The acidic pH generated as a result of D-lactate production further propagates production of D-lactic acid, hence giving rise to a vicious cycle. D-lactic acid accumulation in the blood can cause neurologic symptoms such as delirium, ataxia, and slurred speech. Diagnosis is made by a combination of clinical and laboratory data including special assays for D-lactate. Treatment includes correcting the acidosis and decreasing substrate for D-lactate such as carbohydrates in meals. In addition, antibiotics can be used to clear colonic flora. Although newer techniques for diagnosis and treatment are being developed, clinical diagnosis still holds paramount importance, as there can be many confounders in the diagnosis as will be discussed subsequently.

D-Lactic Acidosis: An Underrecognized Complication of Short Bowel Syndrome

PubMed Central

Kowlgi, N. Gurukripa; Chhabra, Lovely

2015-01-01

D-lactic acidosis or D-lactate encephalopathy is a rare condition that occurs primarily in individuals who have a history of short bowel syndrome. The unabsorbed carbohydrates act as a substrate for colonic bacteria to form D-lactic acid among other organic acids. The acidic pH generated as a result of D-lactate production further propagates production of D-lactic acid, hence giving rise to a vicious cycle. D-lactic acid accumulation in the blood can cause neurologic symptoms such as delirium, ataxia, and slurred speech. Diagnosis is made by a combination of clinical and laboratory data including special assays for D-lactate. Treatment includes correcting the acidosis and decreasing substrate for D-lactate such as carbohydrates in meals. In addition, antibiotics can be used to clear colonic flora. Although newer techniques for diagnosis and treatment are being developed, clinical diagnosis still holds paramount importance, as there can be many confounders in the diagnosis as will be discussed subsequently. PMID:25977687

Distal renal tubular acidosis in two children with acquired hypothyroidism.

PubMed

Guerra-Hernández, Norma E; Ordaz-López, Karen V; Vargas-Poussou, Rosa; Escobar-Pérez, Laura; García-Nieto, Víctor M

2018-04-28

Two cases of children diagnosed with renal tubular acidosis (RTA) associated with autoimmune hypothyroidism are presented. Case 1 developed an intestinal ileus at the age of five in the context of a respiratory problem. The tests performed confirmed metabolic acidosis, hyperchloraemia, hypokalaemia and nephrocalcinosis. Case 2 was diagnosed with hypothyroidism at the age of 11, and with RTA two years later. In both patients, the diagnosis of RTA was verified when decreased maximum urinary pCO 2 was found. In case 2, a proximal bicarbonate leak (type 3 RTA) was also confirmed. This was the first case to be published on the topic. The causes of RTA in patients with hypothyroidism are reviewed. The deleterious effect on the kidneys may be due to the absence of thyroid hormone and/or autoantibodies in the cases of autoimmune hypothyroidism. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Hypokalemic Paralysis: A Hidden Card of Several Autoimmune Diseases

PubMed Central

Velarde-Mejía, Yelitza; Gamboa-Cárdenas, Rocío; Ugarte-Gil, Manuel; Asurza, César Pastor

2017-01-01

Acute hypokalemic paralysis is a rare and potentially fatal condition, with few related causes, one of which highlights distal renal tubular acidosis (dRTA). Distal renal tubular acidosis is a rare complication of several autoimmune diseases such as systemic lupus erythematosus, Sjögren’s syndrome, and Hashimoto thyroiditis. We report a case of a lupic patient who presented rapidly progressive quadriparesis in the context of active renal disease. Research revealed severe refractory hypokalemia, metabolic acidosis, and alkaline urine suggestive of dRTA. We diagnosed Sjögren’s syndrome based on sicca symptoms, an abnormal salivary glands’ nuclear scan and the presence of anti-Ro/SSA and anti-La/SSB. In addition, the finding of thyroid peroxidase, thyroglobulin antibodies, and hypothyroidism led us to the diagnosis of Hashimoto thyroiditis. Due to the active renal involvement on the context of systemic lupus erythematosus and Sjögren’s syndrome, the patient received immunosuppression with rituximab, resulting in a progressive and complete improvement. PMID:28839447

Acidosis promotes invasiveness of breast cancer cells through ROS-AKT-NF-κB pathway

PubMed Central

Gupta, Subash C.; Singh, Ramesh; Pochampally, Radhika; Watabe, Kounosuke; Mo, Yin-Yuan

2014-01-01

It is well known that acidic microenvironment promotes tumorigenesis, however, the underlying mechanism remains largely unknown. In the present study, we show that acidosis promotes invasiveness of breast cancer cells through a series of signaling events. First, our study indicates that NF-κB is a key factor for acidosis-induced cell invasion. Acidosis activates NF-κB without affecting STAT3 activity; knockdown of NF-κB p65 abrogates the acidosis-induced invasion activity. Next, we show that the activation of NF-κB is mediated through phosphorylation and degradation of IκBα; and phosphorylation and nuclear translocation of p65. Upstream to NF-κB signaling, AKT is activated under acidic conditions. Moreover, acidosis induces generation of reactive oxygen species (ROS) which can be suppressed by ROS scavengers, reversing the acidosis-induced activation of AKT and NF-κB, and invasiveness. As a negative regulator of AKT, PTEN is oxidized and inactivated by the acidosis-induced ROS. Finally, inhibition of NADPH oxidase (NOX) suppresses acidosis-induced ROS production, suggesting involvement of NOX in acidosis-induced signaling cascade. Of considerable interest, acidosis-induced ROS production and activation of AKT and NF-κB can be only detected in cancer cells, but not in non-malignant cells. Together, these results demonstrate a cancer specific acidosis-induced signaling cascade in breast cancer cells, leading to cell invasion. PMID:25504433

Distal Renal Tubular Acidosis and Calcium Nephrolithiasis

NASA Astrophysics Data System (ADS)

Moe, Orson W.; Fuster, Daniel G.; Xie, Xiao-Song

2008-09-01

Calcium stones are commonly encountered in patients with congenital distal renal tubular acidosis, a disease of renal acidification caused by mutations in either the vacuolar H+-ATPase (B1 or a4 subunit), anion exchanger-1, or carbonic anhydrase II. Based on the existing database, we present two hypotheses. First, heterozygotes with mutations in B1 subunit of H+-ATPase are not normal but may harbor biochemical abnormalities such as renal acidification defects, hypercalciuria, and hypocitraturia which can predispose them to kidney stone formation. Second, we propose at least two mechanisms by which mutant B1 subunit can impair H+-ATPase: defective pump assembly and defective pump activity.

Diagnosis and Management of Subacute Ruminal Acidosis in Dairy Herds.

PubMed

Oetzel, Garrett R

2017-11-01

Subacute ruminal acidosis (SARA) is a common problem in lactating dairy cows that causes chronic health problems, impairs feed efficiency, and increases the environmental impact of milk production. Low ruminal pH appears to be the main instigator of the pathophysiology of SARA, although other metabolites produced in the rumen may be involved. Inflammatory responses to SARA are variable but important determinants of a cow's response to SARA. SARA can be diagnosed at the herd level by integrating information about clinical signs and on-farm measures of ruminal pH. Prevention of SARA requires excellent feeding management and proper diet formulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Osmolality and respiratory regulation in humans: respiratory compensation for hyperchloremic metabolic acidosis is absent after infusion of hypertonic saline in healthy volunteers.

PubMed

Moen, Vibeke; Brudin, Lars; Rundgren, Mats; Irestedt, Lars

2014-10-01

Several animal studies show that changes in plasma osmolality may influence ventilation. Respiratory depression caused by increased plasma osmolality is interpreted as inhibition of water-dependent thermoregulation because conservation of body fluid predominates at the cost of increased core temperature. Respiratory alkalosis, on the other hand, is associated with a decrease in plasma osmolality and strong ion difference (SID) during human pregnancy. We investigated the hypothesis that osmolality would influence ventilation, so that increased osmolality will decrease ventilation and decreased osmolality will stimulate ventilation in both men and women. Our study participants were healthy volunteers of both sexes (ASA physical status I). Ten men (mean 28 years; range 20-40) and 9 women (mean 33 years; range 22-43) were included. All women participated in both the follicular and luteal phases of the menstrual cycle. Hyperosmolality was induced by IV infusion of hypertonic saline 3%, and hypoosmolality by drinking tap water. Arterial blood samples were collected for analysis of electrolytes, osmolality, and blood gases. Sensitivity to CO2 was determined by rebreathing tests performed before and after the fluid-loading procedures. Infusion of hypertonic saline caused hyperchloremic metabolic acidosis with decreased SID in all subjects. Analysis of pooled data showed absence of respiratory compensation. Baseline arterial PCO2 (PaCO2) mean (SD) 37.8 (2.9) mm Hg remained unaltered, with lowest PaCO2 37.8 (2.9) mm Hg after 100 minutes, P = 0.70, causing a decrease in pH from mean (SD) 7.42 (0.02) to 7.38 (0.02), P < 0.001. Metabolic acidosis was also observed during water loading. Pooled results show that PaCO2 decreased from 38.2 (3.3) mm Hg at baseline to 35.7 (2.8) mm Hg after 80 minutes of drinking water, P = 0.002, and pH remained unaltered: pH 7.43 (0.02) at baseline to pH 7.42 (0.02), P = 0.14, mean difference (confidence interval) = pH -0.007 (-0.017 to 0.003). Our results indicate that osmolality has an influence on ventilation. Respiratory compensation for hyperchloremic metabolic acidosis was suppressed during hyperosmolality. Water loading caused a decrease in plasma osmolality and metabolic acidosis, and although the decrease in SID was smaller compared with salt loading, the expected respiratory compensation was observed. Ventilation was also stimulated in men, therefore independently of progesterone levels. We propose that the influence of osmolality on ventilation consists mainly as depression in conditions of hyperosmolality and that this depression is absent during hypoosmolality.

Ruminal acidosis in beef cattle: the current microbiological and nutritional outlook.

PubMed

Nagaraja, T G; Titgemeyer, E C

2007-06-01

Ruminal acidosis continues to be a common ruminal digestive disorder in beef cattle and can lead to marked reductions in cattle performance. Ruminal acidosis or increased accumulation of organic acids in the rumen reflects imbalance between microbial production, microbial utilization, and ruminal absorption of organic acids. The severity of acidosis, generally related to the amount, frequency, and duration of grain feeding, varies from acute acidosis due to lactic acid accumulation, to subacute acidosis due to accumulation of volatile fatty acids in the rumen. Ruminal microbial changes associated with acidosis are reflective of increased availability of fermentable substrates and subsequent accumulation of organic acids. Microbial changes in the rumen associated with acute acidosis have been well documented. Microbial changes in subacute acidosis resemble those observed during adaptation to grain feeding and have not been well documented. The decrease in ciliated protozoal population is a common feature of both forms of acidosis and may be a good microbial indicator of an acidotic rumen. Other microbial factors, such as endotoxin and histamine, are thought to contribute to the systemic effects of acidosis. Various models have been developed to assess the effects of variation in feed intake, dietary roughage amount and source, dietary grain amount and processing, step-up regimen, dietary addition of fibrous byproducts, and feed additives. Models have been developed to study effects of management considerations on acidosis in cattle previously adapted to grain-based diets. Although these models have provided useful information related to ruminal acidosis, many are inadequate for detecting responses to treatment due to inadequate replication, low feed intakes by the experimental cattle that can limit the expression of acidosis, and the feeding of cattle individually, which reduces experimental variation but limits the ability of researchers to extrapolate the data to cattle performing at industry standards. Optimal model systems for assessing effects of various management and nutritional strategies on ruminal acidosis will require technologies that allow feed intake patterns, ruminal conditions, and animal health and performance to be measured simultaneously in a large number of cattle managed under conditions similar to commercial feed yards. Such data could provide valuable insight into the true extent to which acidosis affects cattle performance.

Acidosis induces reprogramming of cellular metabolism to mitigate oxidative stress

PubMed Central

2013-01-01

Background A variety of oncogenic and environmental factors alter tumor metabolism to serve the distinct cellular biosynthetic and bioenergetic needs present during oncogenesis. Extracellular acidosis is a common microenvironmental stress in solid tumors, but little is known about its metabolic influence, particularly when present in the absence of hypoxia. In order to characterize the extent of tumor cell metabolic adaptations to acidosis, we employed stable isotope tracers to examine how acidosis impacts glucose, glutamine, and palmitate metabolism in breast cancer cells exposed to extracellular acidosis. Results Acidosis increased both glutaminolysis and fatty acid β-oxidation, which contribute metabolic intermediates to drive the tricarboxylic acid cycle (TCA cycle) and ATP generation. Acidosis also led to a decoupling of glutaminolysis and novel glutathione (GSH) synthesis by repressing GCLC/GCLM expression. We further found that acidosis redirects glucose away from lactate production and towards the oxidative branch of the pentose phosphate pathway (PPP). These changes all serve to increase nicotinamide adenine dinucleotide phosphate (NADPH) production and counter the increase in reactive oxygen species (ROS) present under acidosis. The reduced novel GSH synthesis under acidosis may explain the increased demand for NADPH to recycle existing pools of GSH. Interestingly, acidosis also disconnected novel ribose synthesis from the oxidative PPP, seemingly to reroute PPP metabolites to the TCA cycle. Finally, we found that acidosis activates p53, which contributes to both the enhanced PPP and increased glutaminolysis, at least in part, through the induction of G6PD and GLS2 genes. Conclusions Acidosis alters the cellular metabolism of several major metabolites, which induces a significant degree of metabolic inflexibility. Cells exposed to acidosis largely rely upon mitochondrial metabolism for energy generation to the extent that metabolic intermediates are redirected away from several other critical metabolic processes, including ribose and glutathione synthesis. These alterations lead to both a decrease in cellular proliferation and increased sensitivity to ROS. Collectively, these data reveal a role for p53 in cellular metabolic reprogramming under acidosis, in order to permit increased bioenergetic capacity and ROS neutralization. Understanding the metabolic adaptations that cancer cells make under acidosis may present opportunities to generate anti-tumor therapeutic agents that are more tumor-specific. PMID:24359630

Acidosis-Induced Dysfunction of Cortical GABAergic Neurons through Astrocyte-Related Excitotoxicity

PubMed Central

Guan, Sudong; Zhu, Yan; Wang, Jin-Hui

2015-01-01

Background Acidosis impairs cognitions and behaviors presumably by acidification-induced changes in neuronal metabolism. Cortical GABAergic neurons are vulnerable to pathological factors and their injury leads to brain dysfunction. How acidosis induces GABAergic neuron injury remains elusive. As the glia cells and neurons interact each other, we intend to examine the role of the astrocytes in acidosis-induced GABAergic neuron injury. Results Experiments were done at GABAergic cells and astrocytes in mouse cortical slices. To identify astrocytic involvement in acidosis-induced impairment, we induced the acidification in single GABAergic neuron by infusing proton intracellularly or in both neurons and astrocytes by using proton extracellularly. Compared the effects of intracellular acidification and extracellular acidification on GABAergic neurons, we found that their active intrinsic properties and synaptic outputs appeared more severely impaired in extracellular acidosis than intracellular acidosis. Meanwhile, extracellular acidosis deteriorated glutamate transporter currents on the astrocytes and upregulated excitatory synaptic transmission on the GABAergic neurons. Moreover, the antagonists of glutamate NMDA-/AMPA-receptors partially reverse extracellular acidosis-induced injury in the GABAergic neurons. Conclusion Our studies suggest that acidosis leads to the dysfunction of cortical GABAergic neurons by astrocyte-mediated excitotoxicity, in addition to their metabolic changes as indicated previously. PMID:26474076

The frequency and severity of metabolic acidosis related to topiramate.

PubMed

Türe, Hatice; Keskin, Özgül; Çakır, Ülkem; Aykut Bingöl, Canan; Türe, Uğur

2016-12-01

Objective We planned a cross-sectional analysis to determine the frequency and severity of metabolic acidosis in patients taking topiramate while awaiting craniotomy. Methods Eighty patients (18 - 65 years) taking topiramate to control seizures while awaiting elective craniotomy were enrolled. Any signs of metabolic acidosis or topiramate-related side effects were investigated. Blood chemistry levels and arterial blood gases, including lactate, were obtained. The severity of metabolic acidosis was defined according to base excess levels as mild or moderate. Results Blood gas analysis showed that 71% ( n = 57) of patients had metabolic acidosis. The frequency of moderate metabolic acidosis was 56% ( n = 45), while that of mild metabolic acidosis was 15% ( n = 12). A high respiratory rate was reported in only 10% of moderately acidotic patients. Conclusions In patients receiving topiramate, baseline blood gas analysis should be performed preoperatively to determine the presence and severity of metabolic acidosis.

Acidification of rabbit corneal endothelium during contact lens wear in vitro.

PubMed

Giasson, C; Bonanno, J A

1995-04-01

Contact lens wear causes significant epithelial and stromal acidosis. In this study, we tested whether lens wear can cause endothelial acidosis as well. Rabbit corneas were isolated and perfused in vitro. The endothelial intracellular pH (pHi) was measured with a pH sensitive fluorescent probe (BCECF). Three conditions were examined: 1) Polymethylmethacrylate (PMMA) and rigid gas-permeable (RGP) contact lens wear using a range of oxygen transmissibility (Dk/L) from 0 to 121, 2) epithelial hypoxia produced by exposure to oligomycin/sodium azide solution or epithelial perfusion with 100% N2 equilibrated Ringer's solution, and 3) epithelial exposure to Ringer's equilibrated with 5% CO2, balance air. PMMA and RGP contact lens wear acidified endothelial cells by 0.23 +/- 0.01 (n = 23) and 0.11 +/- 0.01 pH units (n = 23), respectively, within twenty min of lens insertion. Epithelial hypoxia, induced by sodium azide and oligomycin, reversibly acidified the endothelium by 0.04 +/- 0.01 pH units (n = 4). However, epithelial hypoxia induced by perfusion with 100% N2 equilibrated Ringer's did not have a significant effect on endothelial pHi. Introduction of 5% CO2 to the epithelium, acidified the endothelium by 0.15 +/- 0.02 pH units (n = 7) within 10 min. We conclude that contact lens wear can significantly acidify corneal endothelial cells. The endothelial pHi change is caused almost exclusively by a build up of CO2 behind the lens; hypoxia having very little contribution. As expected, RGP contact lenses induced less endothelial acidosis than PMMA controls.

Anatomical architecture and responses to acidosis of a novel respiratory neuron group in the high cervical spinal cord (HCRG) of the neonatal rat.

PubMed

Okada, Y; Yokota, S; Shinozaki, Y; Aoyama, R; Yasui, Y; Ishiguro, M; Oku, Y

2009-01-01

It has been postulated that there exists a neuronal mechanism that generates respiratory rhythm and modulates respiratory output pattern in the high cervical spinal cord. Recently, we have found a novel respiratory neuron group in the ventral portion of the high cervical spinal cord, and named it the high cervical spinal cord respiratory group (HCRG). In the present study, we analyzed the detailed anatomical architecture of the HCRG region by double immunostaining of the region using a neuron-specific marker (NeuN) and a marker for motoneurons (ChAT) in the neonatal rat. We found a large number of small NeuN-positive cells without ChAT-immunoreactivity, which were considered interneurons. We also found two and three clusters of motoneurons in the ventral portion of the ventral horn at C1 and C2 levels, respectively. Next, we examined responses of HCRG neurons to respiratory and metabolic acidosis in vitro by voltage-imaging together with cross correlation techniques, i.e., by correlation coefficient imaging, in order to understand the functional role of HCRG neurons. Both respiratory and metabolic acidosis caused the same pattern of changes in their spatiotemporal activation profiles, and the respiratory-related area was enlarged in the HCRG region. After acidosis was introduced, preinspiratory phase-dominant activity was recruited in a number of pixels, and more remarkably inspiratory phase-dominant activity was recruited in a large number of pixels. We suggest that the HCRG composes a local respiratory neuronal network consisting of interneurons and motoneurons and plays an important role in respiratory augmentation in response to acidosis.

The acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) inhibits glutathione synthetase in vitro; a clue to the mechanism of 5-oxoprolinuric acidosis?

PubMed

Walker, Valerie; Mills, Graham A; Anderson, Mary E; Ingle, Brandall L; Jackson, John M; Moss, Charlotte L; Sharrod-Cole, Hayley; Skipp, Paul J

2017-02-01

1. Metabolic acidosis due to accumulation of l-5-oxoproline is a rare, poorly understood, disorder associated with acetaminophen treatment in malnourished patients with chronic morbidity. l-5-Oxoprolinuria signals abnormal functioning of the γ-glutamyl cycle, which recycles and synthesises glutathione. Inhibition of glutathione synthetase (GS) by N-acetyl-p-benzoquinone imine (NAPQI) could contribute to 5-oxoprolinuric acidosis in such patients. We investigated the interaction of NAPQI with GS in vitro. 2. Peptide mapping of co-incubated NAPQI and GS using mass spectrometry demonstrated binding of NAPQI with cysteine-422 of GS, which is known to be essential for GS activity. Computational docking shows that NAPQI is properly positioned for covalent bonding with cysteine-422 via Michael addition and hence supports adduct formation. 3. Co-incubation of 0.77 μM of GS with NAPQI (25-400 μM) decreased enzyme activity by 16-89%. Inhibition correlated strongly with the concentration of NAPQI and was irreversible. 4. NAPQI binds covalently to GS causing irreversible enzyme inhibition in vitro. This is an important novel biochemical observation. It is the first indication that NAPQI may inhibit glutathione synthesis, which is pivotal in NAPQI detoxification. Further studies are required to investigate its biological significance and its role in 5-oxoprolinuric acidosis.

MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast.

PubMed

Baruffini, Enrico; Dallabona, Cristina; Invernizzi, Federica; Yarham, John W; Melchionda, Laura; Blakely, Emma L; Lamantea, Eleonora; Donnini, Claudia; Santra, Saikat; Vijayaraghavan, Suresh; Roper, Helen P; Burlina, Alberto; Kopajtich, Robert; Walther, Anett; Strom, Tim M; Haack, Tobias B; Prokisch, Holger; Taylor, Robert W; Ferrero, Ileana; Zeviani, Massimo; Ghezzi, Daniele

2013-11-01

We report three families presenting with hypertrophic cardiomyopathy, lactic acidosis, and multiple defects of mitochondrial respiratory chain (MRC) activities. By direct sequencing of the candidate gene MTO1, encoding the mitochondrial-tRNA modifier 1, or whole exome sequencing analysis, we identified novel missense mutations. All MTO1 mutations were predicted to be deleterious on MTO1 function. Their pathogenic role was experimentally validated in a recombinant yeast model, by assessing oxidative growth, respiratory activity, mitochondrial protein synthesis, and complex IV activity. In one case, we also demonstrated that expression of wt MTO1 could rescue the respiratory defect in mutant fibroblasts. The severity of the yeast respiratory phenotypes partly correlated with the different clinical presentations observed in MTO1 mutant patients, although the clinical outcome was highly variable in patients with the same mutation and seemed also to depend on timely start of pharmacological treatment, centered on the control of lactic acidosis by dichloroacetate. Our results indicate that MTO1 mutations are commonly associated with a presentation of hypertrophic cardiomyopathy, lactic acidosis, and MRC deficiency, and that ad hoc recombinant yeast models represent a useful system to test the pathogenic potential of uncommon variants, and provide insight into their effects on the expression of a biochemical phenotype. © 2013 The Authors. *Human Mutation published by Wiley Periodicals, Inc.

Acetaminophen toxicity and 5-oxoproline (pyroglutamic acid): a tale of two cycles, one an ATP-depleting futile cycle and the other a useful cycle.

PubMed

Emmett, Michael

2014-01-01

The acquired form of 5-oxoproline (pyroglutamic acid) metabolic acidosis was first described in 1989 and its relationship to chronic acetaminophen ingestion was proposed the next year. Since then, this cause of chronic anion gap metabolic acidosis has been increasingly recognized. Many cases go unrecognized because an assay for 5-oxoproline is not widely available. Most cases occur in malnourished, chronically ill women with a history of chronic acetaminophen ingestion. Acetaminophen levels are very rarely in the toxic range; rather, they are usually therapeutic or low. The disorder generally resolves with cessation of acetaminophen and administration of intravenous fluids. Methionine or N-acetyl cysteine may accelerate resolution and methionine is protective in a rodent model. The disorder has been attributed to glutathione depletion and activation of a key enzyme in the γ-glutamyl cycle. However, the specific metabolic derangements that cause the 5-oxoproline accumulation remain unclear. An ATP-depleting futile 5-oxoproline cycle can explain the accumulation of 5-oxoproline after chronic acetaminophen ingestion. This cycle is activated by the depletion of both glutathione and cysteine. This explanation contributes to our understanding of acetaminophen-induced 5-oxoproline metabolic acidosis and the beneficial role of N-acetyl cysteine therapy. The ATP-depleting futile 5-oxoproline cycle may also play a role in the energy depletions that occur in other acetaminophen-related toxic syndromes.

Reversible Microvascular Hyporeactivity to Acetylcholine During Diabetic Ketoacidosis.

PubMed

Joffre, Jérémie; Bourcier, Simon; Hariri, Geoffroy; Miailhe, Arnaud-Felix; Bigé, Naike; Dumas, Guillaume; Dubée, Vincent; Boelle, Pierre-Yves; Abdallah, Idriss; Baudel, Jean-Luc; Guidet, Bertrand; Maury, Eric; Ait-Oufella, Hafid

2018-05-18

Metabolic acidosis is commonly observed in critically ill patients. Experimental studies suggested that acidosis by itself could impair vascular function, but this has been poorly investigated in human. Prospective observational study. Medical ICU in a tertiary teaching hospital. To assess the relationship between metabolic acidosis severity and microvascular reactivity, we included adult diabetic patients admitted in ICU for ketoacidosis. Microvascular response to acetylcholine iontophoresis was measured at admission (baseline) and after correction of metabolic acidosis (24 hr). None. Thirty-nine patients with diabetic ketoacidosis were included (68% male), with a median age of 43 (31-57) years. At admission, microvascular reactivity negatively correlated with acidosis severity (R = -0.53; p < 0.001). Microvascular response was strongly depressed at pH less than 7.20 (area under the curve, 1,779 [740-3,079] vs 12,944 [4,874-21,596] at pH > 7.20; p < 0.0001). In addition, acidosis severity was significantly correlated with capillary refill time (R = 0.50; p = 0.02). At H24, after rehydration and insulin infusion, clinical and biological disorders were fully corrected. After acidosis correction, microvascular reactivity increased more in patients with severe baseline acidosis (pH < 7.20) than in those with mild baseline acidosis (area under the curve, +453% [213%-1,470%] vs +121% [79%-312%]; p < 0.01). We identified an alteration of microvascular reactivity during metabolic acidosis in critically ill patients with diabetic ketoacidosis. Microvascular hyporeactivity recovered after acidosis correction.

Effects of acute respiratory and metabolic acidosis on diaphragm muscle obtained from rats.

PubMed

Michelet, Pierre; Carreira, Serge; Demoule, Alexandre; Amour, Julien; Langeron, Olivier; Riou, Bruno; Coirault, Catherine

2015-04-01

Acute respiratory acidosis is associated with alterations in diaphragm performance. The authors compared the effects of respiratory acidosis and metabolic acidosis in the rat diaphragm in vitro. Diaphragmatic strips were stimulated in vitro, and mechanical and energetic variables were measured, cross-bridge kinetics calculated, and the effects of fatigue evaluated. An extracellular pH of 7.00 was obtained by increasing carbon dioxide tension (from 25 to 104 mmHg) in the respiratory acidosis group (n = 12) or lowering bicarbonate concentration (from 24.5 to 5.5 mM) in the metabolic acidosis group (n = 12) and the results compared with a control group (n = 12, pH = 7.40) after 20-min exposure. Respiratory acidosis induced a significant decrease in maximum shortening velocity (-33%, P < 0.001), active isometric force (-36%, P < 0.001), and peak power output (-59%, P < 0.001), slowed relaxation, and decreased the number of cross-bridges (-35%, P < 0.001) but not the force per cross-bridge, and impaired recovery from fatigue. Respiratory acidosis impaired more relaxation than contraction, as shown by impairment in contraction-relaxation coupling under isotonic (-26%, P < 0.001) or isometric (-44%, P < 0.001) conditions. In contrast, no significant differences in diaphragmatic contraction, relaxation, or contraction-relaxation coupling were observed in the metabolic acidosis group. In rat diaphragm, acute (20 min) respiratory acidosis induced a marked decrease in the diaphragm contractility, which was not observed in metabolic acidosis.

A case of D-lactic acid encephalopathy associated with use of probiotics.

PubMed

Munakata, Shun; Arakawa, Chikako; Kohira, Ryutaro; Fujita, Yukihiko; Fuchigami, Tatsuo; Mugishima, Hideo

2010-09-01

A five year old girl was admitted to the hospital for evaluation of intermittent ataxia. She had undergone serial resections of the small intestine after birth, resulting in short bowel syndrome. Lactomin was prescribed for watery diarrhea at twice the regular dose 2 weeks before the onset of neurologic symptoms. D-lactic acidosis was diagnosed on the basis of a plasma D-lactate level of 5.537 mmol/l. Lactomin was discontinued, and she was treated with sodium bicarbonate and oral antibiotics. The probiotics the patient had taken were likely the cause of D-lactic acidosis and should therefore be avoided in patients with short bowel syndrome. Copyright 2009 Elsevier B.V. All rights reserved.

[Treatment with metformin in type 2 diabetes mellitus - new routines when renal function is reduced and in connection with administration of iodine contrast media].

PubMed

Sterner, Gunnar; Frid, Anders

2018-04-03

Metformin is eliminated through glomerular filtration and tubular secretion in the kidneys. New guidelines recommend use of metformin down to a GFR of 30 mL/min under the condition that the dose is adjusted. As the risk of inducing lactic acidosis is very low in connection with administration of iodine contrast media, new recommendations in Sweden say that metformin must be stopped only when GFR is below 45 mL/min. Determination of metformin levels in serum is useful to guide therapeutic dose when GFR is low but also to confirm that lactic acidosis is caused by metformin.

Hypercapnic acidosis attenuates ventilation-induced lung injury by a nuclear factor-κB-dependent mechanism.

PubMed

Contreras, Maya; Ansari, Bilal; Curley, Gerard; Higgins, Brendan D; Hassett, Patrick; O'Toole, Daniel; Laffey, John G

2012-09-01

Hypercapnic acidosis protects against ventilation-induced lung injury. We wished to determine whether the beneficial effects of hypercapnic acidosis in reducing stretch-induced injury were mediated via inhibition of nuclear factor-κB, a key transcriptional regulator in inflammation, injury, and repair. Prospective randomized animal study. University research laboratory. Adult male Sprague-Dawley rats. In separate experimental series, the potential for hypercapnic acidosis to attenuate moderate and severe ventilation-induced lung injury was determined. In each series, following induction of anesthesia and tracheostomy, Sprague-Dawley rats were randomized to (normocapnia; FICO2 0.00) or (hypercapnic acidosis; FICO2 0.05), subjected to high stretch ventilation, and the severity of lung injury and indices of activation of the nuclear factor-κB pathway were assessed. Subsequent in vitro experiments examined the potential for hypercapnic acidosis to reduce pulmonary epithelial inflammation and injury induced by cyclic mechanical stretch. The role of the nuclear factor-κB pathway in hypercapnic acidosis-mediated protection from stretch injury was then determined. Hypercapnic acidosis attenuated moderate and severe ventilation-induced lung injury, as evidenced by improved oxygenation, compliance, and reduced histologic injury compared to normocapnic conditions. Hypercapnic acidosis reduced indices of inflammation such as interleukin-6 and bronchoalveolar lavage neutrophil infiltration. Hypercapnic acidosis reduced the decrement of the nuclear factor-κB inhibitor IκBα and reduced the generation of cytokine-induced neutrophil chemoattractant-1. Hypercapnic acidosis reduced cyclic mechanical stretch-induced nuclear factor-κB activation, reduced interleukin-8 production, and decreased epithelial injury and cell death compared to normocapnia. Hypercapnic acidosis attenuated ventilation-induced lung injury independent of injury severity and decreased mechanical stretch-induced epithelial injury and death, via a nuclear factor-κB-dependent mechanism.

Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis.

PubMed

Silva, Pedro Henrique Imenez; Girardi, Adriana Castello Costa; Neri, Elida Adalgisa; Rebouças, Nancy Amaral

2012-04-01

The Na(+/)H(+) exchanger isoform 3 (NHE3) is essential for HCO(3)(-) reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO(3)(-) concentration in the cell culture medium and respiratory acidosis by increasing CO(2) tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 ± 0.02) and severe (6.95 ± 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 ± 0.03) and severe (6.86 ± 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.

Interaction of metabolic and respiratory acidosis with α and β-adrenoceptor stimulation in rat myocardium.

PubMed

Biais, Matthieu; Jouffroy, Romain; Carillion, Aude; Feldman, Sarah; Jobart-Malfait, Aude; Riou, Bruno; Amour, Julien

2012-12-01

The effects of acute respiratory versus metabolic acidosis on the myocardium and their consequences on adrenoceptor stimulation remain poorly described. We compared the effects of metabolic and respiratory acidosis on inotropy and lusitropy in rat myocardium and their effects on the responses to α- and β-adrenoceptor stimulations. The effects of acute respiratory and metabolic acidosis (pH 7.10) and their interactions with α and β-adrenoceptor stimulations were studied in isolated rat left ventricular papillary muscle (n=8 per group). Intracellular pH was measured using confocal microscopy and a pH-sensitive fluorophore in isolated rat cardiomyocytes. Data are mean percentages of baseline±SD. Respiratory acidosis induced more pronounced negative inotropic effects than metabolic acidosis did both in isotonic (45±3 versus 63±6%, P<0.001) and isometric (44±5 versus 64±3%, P<0.001) conditions concomitant with a greater decrease in intracellular pH (6.85±0.07 versus 7.12±0.07, P<0.001). The response to α-adrenergic stimulation was not modified by respiratory or metabolic acidosis. The inotropic response to β-adrenergic stimulation was impaired only in metabolic acidosis (137±12 versus 200±33%, P<0.001), but this effect was not observed with administration of forskolin or dibutiryl-cyclic adenosine monophosphate. This effect might be explained by a change in transmembrane pH gradient only observed with metabolic acidosis. The lusitropic response to β-adrenergic stimulation was not modified by respiratory or metabolic acidosis. Acute metabolic and respiratory acidosis induce different myocardial effects related to different decreases in intracellular pH. Only metabolic acidosis impairs the positive inotropic effect of β-adrenergic stimulation.

Metformin-associated lactic acidosis (MALA): Moving towards a new paradigm.

PubMed

Lalau, Jean-Daniel; Kajbaf, Farshad; Protti, Alessandro; Christensen, Mette M; De Broe, Marc E; Wiernsperger, Nicolas

2017-11-01

Although metformin has been used for over 60 years, the balance between the drug's beneficial and adverse effects is still subject to debate. Following an analysis of how cases of so-called "metformin-associated lactic acidosis" (MALA) are reported in the literature, the present article reviews the pitfalls to be avoided when assessing the purported association between metformin and lactic acidosis. By starting from pathophysiological considerations, we propose a new paradigm for lactic acidosis in metformin-treated patients. Metformin therapy does not necessarily induce metformin accumulation, just as metformin accumulation does not necessarily induce hyperlactatemia, and hyperlactatemia does not necessarily induce lactic acidosis. In contrast to the conventional view, MALA probably accounts for a smaller proportion of cases than either metformin-unrelated lactic acidosis or metformin-induced lactic acidosis. Lastly, this review highlights the need for substantial improvements in the reporting of cases of lactic acidosis in metformin-treated patients. Accordingly, we propose a check-list as a guide to clinical practice. © 2017 John Wiley & Sons Ltd.

Lactic acidosis occurrence during exercises in the smoke chamber in a 53-year-old firefighter with no significant medical history.

PubMed

Bronisz, Agata; Spychalska, Magdalena; Szafrańska, Małgorzata

2014-04-01

Lactic acidosis is a form of metabolic acidosis with a high anion gap, reduced rate of arterial blood pH under 7.35 mmol/l, and lactic acid concentration over 7 mmol/l. In the literature we can find some descriptions of the cases of lactic acidosis in patients with severe systemic diseases (cancer, acquired immunodeficiency syndrome, sepsis, diabetes with cardiovascular disease and after organ transplantations). We present the case of lactic acidosis in a patient with no chronic disease--a firefighter in whom lactic acidosis has developed during standard exercises in the smoke chamber.

A Quick Reference on Respiratory Acidosis.

PubMed

Johnson, Rebecca A

2017-03-01

Respiratory acidosis, or primary hypercapnia, occurs when carbon dioxide production exceeds elimination via the lung and is mainly owing to alveolar hypoventilation. Concurrent increases in Paco 2 , decreases in pH and compensatory increases in blood HCO 3 - concentration are associated with respiratory acidosis. Respiratory acidosis can be acute or chronic, with initial metabolic compensation to increase HCO 3 - concentrations by intracellular buffering. Chronic respiratory acidosis results in longer lasting increases in renal reabsorption of HCO 3 - . Alveolar hypoventilation and resulting respiratory acidosis may also be associated with hypoxemia, especially evident when patients are inspiring room air (20.9% O 2 ). Copyright © 2016 Elsevier Inc. All rights reserved.

Fatal lactic acidosis in hepatitis B virus-associated decompensated cirrhosis treated with tenofovir: A case report.

PubMed

Jung, Tae Yang; Jun, Dae Won; Lee, Kang Nyeong; Lee, Hang Lak; Lee, Oh Young; Yoon, Byung Chul; Choi, Ho Soon

2017-06-01

Recently tenofovir disoproxil fumarate (TDF) has been widely used as a first-line therapy for chronic hepatitis B (CHB) infection. Although TDF demonstrates successful viral suppression, the possibility of renal failure and lactic acidosis has been proposed with TDF administration, especially in human immunodeficiency virus co-infected patients. However, TDF induced lactic acidosis has never been reported in CHB mono-infected patients. A 59-year-old man received TDF for hepatitis B associated with cirrhosis. After ten days of TDF administration, nausea, vomiting and abdominal pain developed. High anion gap acidosis with elevated lactate level (pH 7.341, pCO2 29.7 mmHg, HCO3- 15.6mmHg, lactate 3.2mmol/L, anion gap 15.4 mEq/L) was developed. With no infection, normal diagnostic paracentesis, and urinalysis together with high anion gap and increased blood lactate levels suggested lactic acidosis. TDF was stopped, and haemodialysis was performed to control lactic acidosis. Although stopping TDF instantly and treating lactic acidosis using hemodialysis, the patient died. Although, Fatal lactic acidosis is very rare in TDF patient, however, decompensated cirrhotic patients should be closely observed to keep the possibility of lactic acidosis in mind.

[Metabolic acidosis].

PubMed

Regolisti, Giuseppe; Fani, Filippo; Antoniotti, Riccardo; Castellano, Giuseppe; Cremaschi, Elena; Greco, Paolo; Parenti, Elisabetta; Morabito, Santo; Sabatino, Alice; Fiaccadori, Enrico

2016-01-01

Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

Anoxia and Acidosis Tolerance of the Heart in an Air-Breathing Fish (Pangasianodon hypophthalmus).

PubMed

Joyce, William; Gesser, Hans; Bayley, Mark; Wang, Tobias

2015-01-01

Air breathing has evolved repeatedly in fishes and may protect the heart during stress. We investigated myocardial performance in the air-breathing catfish Pangasianodon hypophthalmus, a species that can withstand prolonged exposure to severe hypoxia and acidosis. Isometric ventricular preparations were exposed to anoxia, lactic acidosis, hypercapnic acidosis, and combinations of these treatments. Ventricular preparations were remarkably tolerant to anoxia, exhibiting an inotropic reduction of only 40%, which fully recovered during reoxygenation. Myocardial anoxia tolerance was unaffected by physiologically relevant elevations of bicarbonate concentration, in contrast to previous results in other fishes. Both lactic acidosis (5 mM; pH 7.10) and hypercapnic acidosis (10% CO2; pH 6.70) elicited a biphasic response, with an initial and transient decrease in force followed by overcompensation above control values. Spongy myocardial preparations were significantly more tolerant to hypercapnic acidosis than compact myocardial preparations. While ventricular preparations were tolerant to the isolated effects of anoxia and acidosis, their combination severely impaired myocardial performance and contraction kinetics. This suggests that air breathing may be a particularly important myocardial oxygen source during combined anoxia and acidosis, which may occur during exercise or environmental stress.

Gender-specific association between dietary acid load and total lean body mass and its dependency on protein intake in seniors

USDA-ARS?s Scientific Manuscript database

Background: Sarcopenia, the age-related decline of muscle mass, is one of the most important causes of loss of physical function and falls in seniors. Causes of sarcopenia are multiple, but there is evidence that diet-related mild metabolic acidosis may play a role in the development of skeletal mus...

Multiorgan Failure and Refractory Lactic Acidosis due to Pasteurella multocida Septicemia in a Patient with No Animal Exposure

PubMed Central

Pena, Damaris; Santana, Yaneidy; Perez Lara, Jose; Gonzalez, Efrain

2018-01-01

Introduction Pasteurella multocida is a gram-negative coccobacillus pathogenic to animals. It can cause infection in humans by a bite, scratch, or lick from a cat or dog. P. multocida can cause a variety of infections in humans, including cellulitis, osteomyelitis, endocarditis, peritonitis, and septic shock. Case Presentation A 56-year-old male presented to our hospital with a 2-day history of fever, abdominal pain, nausea, and vomiting. He denied exposure to cats, dogs or other pets. He had severe respiratory distress requiring ventilator support, profound septic shock requiring multiple vasopressors, severe lactic acidosis, and renal failure requiring emergent hemodialysis. Blood cultures confirmed the presence of P. multocida. The patient subsequently died of cardiopulmonary arrest due to multiorgan failure with refractory shock. Conclusion P. multocida septicemia can lead to septic shock. Early identification of this organism may decrease mortality. Although our patient had no known cat or dog exposure, physicians should enquire about a history of animal exposure when a patient presents with an infection with no obvious cause. PMID:29765783

Four siblings with distal renal tubular acidosis and nephrocalcinosis, neurobehavioral impairment, short stature, and distinctive facial appearance: a possible new autosomal recessive syndrome.

PubMed

Faqeih, Eissa; Al-Akash, Samhar I; Sakati, Nadia; Teebi, Prof Ahmad S

2007-09-01

We report on four siblings (three males, one female) born to first cousin Arab parents with the constellation of distal renal tubular acidosis (RTA), small kidneys, nephrocalcinosis, neurobehavioral impairment, short stature, and distinctive facial features. They presented with early developmental delay with subsequent severe mental, behavioral and social impairment and autistic-like features. Their facial features are unique with prominent cheeks, well-defined philtrum, large bulbous nose, V-shaped upper lip border, full lower lip, open mouth with protruded tongue, and pits on the ear lobule. All had proteinuria, hypercalciuria, hypercalcemia, and normal anion-gap metabolic acidosis. Renal ultrasound examinations revealed small kidneys, with varying degrees of hyperechogenicity and nephrocalcinosis. Additional findings included dilated ventricles and cerebral demyelination on brain imaging studies. Other than distal RTA, common causes of nephrocalcinosis were excluded. The constellation of features in this family currently likely represents a possibly new autosomal recessive syndrome providing further evidence of heterogeneity of nephrocalcinosis syndromes. Copyright 2007 Wiley-Liss, Inc.

Pharmacologically-induced metabolic acidosis: a review.

PubMed

Liamis, George; Milionis, Haralampos J; Elisaf, Moses

2010-05-01

Metabolic acidosis may occasionally develop in the course of treatment with drugs used in everyday clinical practice, as well as with the exposure to certain chemicals. Drug-induced metabolic acidosis, although usually mild, may well be life-threatening, as in cases of lactic acidosis complicating antiretroviral therapy or treatment with biguanides. Therefore, a detailed medical history, with special attention to the recent use of culprit medications, is essential in patients with acid-base derangements. Effective clinical management can be handled through awareness of the adverse effect of certain pharmaceutical compounds on the acid-base status. In this review, we evaluate relevant literature with regard to metabolic acidosis associated with specific drug treatment, and discuss the clinical setting and underlying pathophysiological mechanisms. These mechanisms involve renal inability to excrete the dietary H+ load (including types I and IV renal tubular acidoses), metabolic acidosis owing to increased H+ load (including lactic acidosis, ketoacidosis, ingestion of various substances, administration of hyperalimentation solutions and massive rhabdomyolysis) and metabolic acidosis due to HCO3- loss (including gastrointestinal loss and type II renal tubular acidosis). Determinations of arterial blood gases, the serum anion gap and, in some circumstances, the serum osmolar gap are helpful in delineating the pathogenesis of the acid-base disorder. In all cases of drug-related metabolic acidosis, discontinuation of the culprit medications and avoidance of readministration is advised.

Phenformin-associated lactic acidosis due to imported phenformin.

PubMed

Lu, H C; Parikh, P P; Lorber, D L

1996-12-01

To emphasize the continued incidence of phenformin-associated lactic acidosis. We report a case of phenformin-associated lactic acidosis in a Chinese man who received phenformin while in China. Diagnosis was made; the patient was treated appropriately and survived. Phenformin-associated lactic acidosis may still occur in the U.S.

Drug-Induced Metabolic Acidosis

PubMed Central

Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W.

2015-01-01

Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs’ characteristics. PMID:26918138

Developmental and Reproductive Toxicology of Methanol

EPA Science Inventory

Methanol is a high production volume chemical used as a feedstock for chemical syntheses and as a solvent and fuel additive. Methanol is acutely toxic to humans, causing acidosis, blindness in death at high dosages, but its developmental and reproductive toxicity in humans is poo...

Effects of desmopressin on platelet function under conditions of hypothermia and acidosis: an in vitro study using multiple electrode aggregometry*.

PubMed

Hanke, A A; Dellweg, C; Kienbaum, P; Weber, C F; Görlinger, K; Rahe-Meyer, N

2010-07-01

Hypothermia and acidosis lead to an impairment of coagulation. It has been demonstrated that desmopressin improves platelet function under hypothermia. We tested platelet function ex vivo during hypothermia and acidosis. Blood samples were taken from 12 healthy subjects and assigned as follows: normal pH, pH 7.2, and pH 7.0, each with and without incubation with desmopressin. Platelet aggregation was assessed by multiple electrode aggregometry. Baseline was normal pH and 36 degrees C. The other samples were incubated for 30 min and measured at 32 degrees C. Acidosis significantly impaired aggregation. Desmopressin significantly increased aggregability during hypothermia and acidosis regardless of pH, but did not return it to normal values at low pH. During acidosis and hypothermia, acidosis should be corrected first; desmopressin can then be administered to improve platelet function as a bridge until normothermia can be achieved.

Activation of GPR4 by Acidosis Increases Endothelial Cell Adhesion through the cAMP/Epac Pathway

PubMed Central

Leffler, Nancy R.; Asch, Adam S.; Witte, Owen N.; Yang, Li V.

2011-01-01

Endothelium-leukocyte interaction is critical for inflammatory responses. Whereas the tissue microenvironments are often acidic at inflammatory sites, the mechanisms by which cells respond to acidosis are not well understood. Using molecular, cellular and biochemical approaches, we demonstrate that activation of GPR4, a proton-sensing G protein-coupled receptor, by isocapnic acidosis increases the adhesiveness of human umbilical vein endothelial cells (HUVECs) that express GPR4 endogenously. Acidosis in combination with GPR4 overexpression further augments HUVEC adhesion with U937 monocytes. In contrast, overexpression of a G protein signaling-defective DRY motif mutant (R115A) of GPR4 does not elicit any increase of HUVEC adhesion, indicating the requirement of G protein signaling. Downregulation of GPR4 expression by RNA interference reduces the acidosis-induced HUVEC adhesion. To delineate downstream pathways, we show that inhibition of adenylate cyclase by inhibitors, 2′,5′-dideoxyadenosine (DDA) or SQ 22536, attenuates acidosis/GPR4-induced HUVEC adhesion. Consistently, treatment with a cAMP analog or a Gi signaling inhibitor increases HUVEC adhesiveness, suggesting a role of the Gs/cAMP signaling in this process. We further show that the cAMP downstream effector Epac is important for acidosis/GPR4-induced cell adhesion. Moreover, activation of GPR4 by acidosis increases the expression of vascular adhesion molecules E-selectin, VCAM-1 and ICAM-1, which are functionally involved in acidosis/GPR4-mediated HUVEC adhesion. Similarly, hypercapnic acidosis can also activate GPR4 to stimulate HUVEC adhesion molecule expression and adhesiveness. These results suggest that acidosis/GPR4 signaling regulates endothelial cell adhesion mainly through the Gs/cAMP/Epac pathway and may play a role in the inflammatory response of vascular endothelial cells. PMID:22110680

Effects of hypercapnia and NO synthase inhibition in sustained hypoxic pulmonary vasoconstriction.

PubMed

Ketabchi, Farzaneh; Ghofrani, Hossein A; Schermuly, Ralph T; Seeger, Werner; Grimminger, Friedrich; Egemnazarov, Bakytbek; Shid-Moosavi, S Mostafa; Dehghani, Gholam A; Weissmann, Norbert; Sommer, Natascha

2012-01-31

Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange during local acute (0-30 min), as well as sustained (> 30 min) hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined. We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate), and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min) and endothelial permeability. In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-NG-Nitroarginine (L-NNA), a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS), decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc). This increase disappeared after administration of 1400 W. Hypercapnia with and without acidosis increased HPV during conditions of sustained hypoxia. The increase of sustained HPV and endothelial permeability in hypoxic hypercapnia without acidosis was iNOS dependent.

Prevalence and Correlates of Metabolic Acidosis among Patients with Homozygous Sickle Cell Disease

PubMed Central

Maurel, Stéphane; Stankovic Stojanovic, Katia; Avellino, Virginie; Girshovich, Alexey; Letavernier, Emmanuel; Grateau, Gilles; Baud, Laurent; Girot, Robert; Lionnet, Francois

2014-01-01

Background and objectives Very few studies report acid base disorders in homozygous patients with sickle cell anemia (SCA) and describe incomplete renal acidosis rather than true metabolic acidosis, the prevalence of which is unknown and presumably low. This study aimed to assess the prevalence of metabolic acidosis and to identify its risk factors and mechanisms. Design, setting, participants, & measurements This study retrospectively analyzed 411 homozygous patients with SCA with a GFR≥60 ml/min per 1.73 m2, referred in a single center between 2007 and 2012. Acidosis and nonacidosis groups were compared for clinical and biologic data including SCA complications and hemolytic parameters. A subgroup of 65 patients with SCA, referred for a measured GFR evaluation in the setting of sickle cell–associated nephropathy, was further analyzed in order to better characterize metabolic acidosis. Results Metabolic acidosis was encountered in 42% of patients with SCA, with a higher prevalence in women (52% versus 27% in men; P<0.001). Several hemolytic biomarkers, such as lactate dehydrogenase, were different between the acidosis and nonacidosis groups (P=0.02 and P=0.03 in men and women, respectively), suggesting higher hemolytic activity in the former group. To note, fasting urine osmolality was low in the whole study population and was significantly lower in men with SCA in the acidosis group (392 versus 427 mOsm/kg; P=0.01). SCA subgroup analysis confirmed metabolic acidosis with a normal anion gap in 14 patients, characterized by a lower urinary pH (P<0.02) and no increase in urinary ammonium. Serum potassium, plasma renin, and aldosterone were similar between the two groups and thus could not explain impaired urinary ammonium excretion. Conclusions These results suggest that the prevalence of metabolic acidosis in patients with SCA is underestimated and related to impaired ammonium availability possibly due to an altered corticopapillary gradient. Future studies should evaluate whether chronic metabolic acidosis correction may be beneficial in this population, especially in bone remodeling. PMID:24458070

Clinical predictors and outcome of metabolic acidosis in under-five children admitted to an urban hospital in Bangladesh with diarrhea and pneumonia.

PubMed

Chisti, Mohammod J; Ahmed, Tahmeed; Ashraf, Hasan; Faruque, A S G; Bardhan, Pradip K; Dey, Sanjoy Kumer; Huq, Sayeeda; Das, Sumon Kumar; Salam, Mohammed A

2012-01-01

Clinical features of metabolic acidosis and pneumonia frequently overlap in young diarrheal children, resulting in differentiation from each other very difficult. However, there is no published data on the predictors of metabolic acidosis in diarrheal children also having pneumonia. Our objective was to evaluate clinical predictors of metabolic acidosis in under-five diarrheal children with radiological pneumonia, and their outcome. We prospectively enrolled all under-five children (n = 164) admitted to the Special Care Ward (SCW) of the Dhaka Hospital of icddr, b between September and December 2007 with diarrhea and radiological pneumonia who also had their total serum carbon-dioxide estimated. We compared the clinical features and outcome of children with radiological pneumonia and diarrhea with (n = 98) and without metabolic acidosis (n = 66). Children with metabolic acidosis more often had higher case-fatality (16% vs. 5%, p = 0.039) compared to those without metabolic acidosis on admission. In logistic regression analysis, after adjusting for potential confounders such as age of the patient, fever on admission, and severe wasting, the independent predictors of metabolic acidosis in under-five diarrheal children having pneumonia were clinical dehydration (OR 3.57, 95% CI 1.62-7.89, p = 0.002), and low systolic blood pressure even after full rehydration (OR 1.02, 95% CI 1.01-1.04, p = 0.005). Proportions of children with cough, respiratory rate/minute, lower chest wall indrawing, nasal flaring, head nodding, grunting respiration, and cyanosis were comparable (p>0.05) among the groups. Under-five diarrheal children with radiological pneumonia having metabolic acidosis had frequent fatal outcome than those without acidosis. Clinical dehydration and persistent systolic hypotension even after adequate rehydration were independent clinical predictors of metabolic acidosis among the children. However, metabolic acidosis in young diarrheal children had no impact on the diagnostic clinical features of radiological pneumonia which underscores the importance of early initiation of appropriate antibiotics to combat morbidity and deaths in such population.

Understanding lactic acidosis in paracetamol (acetaminophen) poisoning

PubMed Central

Shah, Anoop D; Wood, David M; Dargan, Paul I

2011-01-01

Paracetamol (acetaminophen) is one of the most commonly taken drugs in overdose in many areas of the world, and the most common cause of acute liver failure in both the UK and USA. Paracetamol poisoning can result in lactic acidosis in two different scenarios. First, early in the course of poisoning and before the onset of hepatotoxicity in patients with massive ingestion; a lactic acidosis is usually associated with coma. Experimental evidence from studies in whole animals, perfused liver slices and cell cultures has shown that the toxic metabolite of paracetamol, N-acetyl-p-benzo-quinone imine, inhibits electron transfer in the mitochondrial respiratory chain and thus inhibits aerobic respiration. This occurs only at very high concentrations of paracetamol, and precedes cellular injury by several hours. The second scenario in which lactic acidosis can occur is later in the course of paracetamol poisoning as a consequence of established liver failure. In these patients lactate is elevated primarily because of reduced hepatic clearance, but in shocked patients there may also be a contribution of peripheral anaerobic respiration because of tissue hypoperfusion. In patients admitted to a liver unit with paracetamol hepatotoxicity, the post-resuscitation arterial lactate concentration has been shown to be a strong predictor of mortality, and is included in the modified King's College criteria for consideration of liver transplantation. We would therefore recommend that post-resuscitation lactate is measured in all patients with a severe paracetamol overdose resulting in either reduced conscious level or hepatic failure. PMID:21143497

[An autopsy case of neonatal lactic acidosis].

PubMed

Giordano, G; Corradi, D; D'Adda, T; Melissari, M

2001-02-01

Defects in mitochondrial enzymes, such as pyruvate dehydrogenase and cytochrome oxidase, cause hereditary disorders which lead to modifications in cellular pH due to the accumulation of pyruvate and lactic acid. Mitochondrial diseases include severe neonatal diseases and less severe forms of adult diseases. We report the case of lactic acidosis in a newborn girl who was delivered at 36 weeks of gestation and who died 3 months after birth. Her family history revealed a relative with tetraparesis and mental retardation. Her clinical findings, such as tonic-clonic convulsions and accumulation of pyruvate and lactic acid in blood, urine and cerebrospinal fluid, were refractory to treatment and developed soon after birth. Ultrasound scans of the brain some days before death revealed cerebral atrophy with ventricular dilatation and thinning of the corpus callosum and septum pellucidum. The clinical diagnosis of metabolic lactic acidosis was confirmed by macroscopic, microscopic and ultrastructural findings seen at autopsy. On macroscopic examination, the heart was hypertrophic, and the brain was atrophic with ventricular dilatation and thinning of corpus callosum. Small cystic lesions were present in the basal ganglia. On microscopic examination, the latter were characterized by loss of neurons, gliosis and capillary proliferation. Ultrastructural examination of the heart and skeletal muscle showed lysis of myofibrils, mitochondrial pleomorphism and hyperplasia, and crystalline inclusion in mitochondria and in the matrix compartment. In reporting this case, we emphasize the importance of accurate postmortem examination and clinical data for the diagnosis of metabolic lactic acidosis.

Noninvasive ventilation for severely acidotic patients in respiratory intermediate care units : Precision medicine in intermediate care units.

PubMed

Masa, Juan F; Utrabo, Isabel; Gomez de Terreros, Javier; Aburto, Myriam; Esteban, Cristóbal; Prats, Enric; Núñez, Belén; Ortega-González, Ángel; Jara-Palomares, Luis; Martin-Vicente, M Jesus; Farrero, Eva; Binimelis, Alicia; Sala, Ernest; Serrano-Rebollo, José C; Barrot, Emilia; Sánchez-Oro-Gomez, Raquel; Fernández-Álvarez, Ramón; Rodríguez-Jerez, Francisco; Sayas, Javier; Benavides, Pedro; Català, Raquel; Rivas, Francisco J; Egea, Carlos J; Antón, Antonio; Peñacoba, Patricia; Santiago-Recuerda, Ana; Gómez-Mendieta, M A; Méndez, Lidia; Cebrian, José J; Piña, Juan A; Zamora, Enrique; Segrelles, Gonzalo

2016-07-07

Severe acidosis can cause noninvasive ventilation (NIV) failure in chronic obstructive pulmonary disease (COPD) patients with acute hypercapnic respiratory failure (AHRF). NIV is therefore contraindicated outside of intensive care units (ICUs) in these patients. Less is known about NIV failure in patients with acute cardiogenic pulmonary edema (ACPE) and obesity hypoventilation syndrome (OHS). Therefore, the objective of the present study was to compare NIV failure rates between patients with severe and non-severe acidosis admitted to a respiratory intermediate care unit (RICU) with AHRF resulting from ACPE, COPD or OHS. We prospectively included acidotic patients admitted to seven RICUs, where they were provided NIV as an initial ventilatory support measure. The clinical characteristics, pH evolutions, hospitalization or RICU stay durations and NIV failure rates were compared between patients with a pH ≥ 7.25 and a pH < 7.25. Logistic regression analysis was performed to determine the independent risk factors contributing to NIV failure. We included 969 patients (240 with ACPE, 540 with COPD and 189 with OHS). The baseline rates of severe acidosis were similar among the groups (45 % in the ACPE group, 41 % in the COPD group, and 38 % in the OHS group). Most of the patients with severe acidosis had increased disease severity compared with those with non-severe acidosis: the APACHE II scores were 21 ± 7.2 and 19 ± 5.8 for the ACPE patients (p < 0.05), 20 ± 5.7 and 19 ± 5.1 for the COPD patients (p < 0.01) and 18 ± 5.9 and 17 ± 4.7 for the OHS patients, respectively (NS). The patients with severe acidosis also exhibited worse arterial blood gas parameters: the PaCO2 levels were 87 ± 22 and 70 ± 15 in the ACPE patients (p < 0.001), 87 ± 21 and 76 ± 14 in the COPD patients, and 83 ± 17 and 74 ± 14 in the OHS patients (NS)., respectively Further, the patients with severe acidosis required a longer duration to achieve pH normalization than those with non-severe acidosis (patients with a normalized pH after the first hour: ACPE, 8 % vs. 43 %, p < 0.001; COPD, 11 % vs. 43 %, p < 0.001; and OHS, 13 % vs. 51 %, p < 0.001), and they had longer RICU stays, particularly those in the COPD group (ACPE, 4 ± 3.1 vs. 3.6 ± 2.5, NS; COPD, 5.1 ± 3 vs. 3.6 ± 2.1, p < 0.001; and OHS, 4.3 ± 2.6 vs. 3.7 ± 3.2, NS). The NIV failure rates were similar between the patients with severe and non-severe acidosis in the three disease groups (ACPE, 16 % vs. 12 %; COPD, 7 % vs. 7 %; and OHS, 11 % vs. 4 %). No common predictive factor for NIV failure was identified among the groups. ACPE, COPD and OHS patients with AHRF and severe acidosis (pH ≤ 7.25) who are admitted to an RICU can be successfully treated with NIV in these units. These results may be used to determine precise RICU admission criteria.

Acetaminophen Toxicity and 5-Oxoproline (Pyroglutamic Acid): A Tale of Two Cycles, One an ATP-Depleting Futile Cycle and the Other a Useful Cycle

PubMed Central

2014-01-01

Summary The acquired form of 5-oxoproline (pyroglutamic acid) metabolic acidosis was first described in 1989 and its relationship to chronic acetaminophen ingestion was proposed the next year. Since then, this cause of chronic anion gap metabolic acidosis has been increasingly recognized. Many cases go unrecognized because an assay for 5-oxoproline is not widely available. Most cases occur in malnourished, chronically ill women with a history of chronic acetaminophen ingestion. Acetaminophen levels are very rarely in the toxic range; rather, they are usually therapeutic or low. The disorder generally resolves with cessation of acetaminophen and administration of intravenous fluids. Methionine or N-acetyl cysteine may accelerate resolution and methionine is protective in a rodent model. The disorder has been attributed to glutathione depletion and activation of a key enzyme in the γ-glutamyl cycle. However, the specific metabolic derangements that cause the 5-oxoproline accumulation remain unclear. An ATP-depleting futile 5-oxoproline cycle can explain the accumulation of 5-oxoproline after chronic acetaminophen ingestion. This cycle is activated by the depletion of both glutathione and cysteine. This explanation contributes to our understanding of acetaminophen-induced 5-oxoproline metabolic acidosis and the beneficial role of N-acetyl cysteine therapy. The ATP-depleting futile 5-oxoproline cycle may also play a role in the energy depletions that occur in other acetaminophen-related toxic syndromes. PMID:24235282

D-lactic acidosis mediated neuronal encephalopathy in acute lymphoblastic leukemia patient: an under diagnosis.

PubMed

Mendu, Damodara Rao; Fleisher, Martin; McCash, Samuel I; Pessin, Melissa S; Ramanathan, Lakshmi V

2015-02-20

D-lactic acidosis, also referred as D-lactate encephalopathy, has been reported in patients with short bowl syndrome (SBS). The neurologic symptoms include altered mental status, slurred speech, and ataxia. Onset of neurological symptoms is accompanied by metabolic acidosis and high anion gap. We present here a case of D-lactic acidosis in a patient with acute lymphoblastic leukemia (ALL) who developed severe neurological symptoms and metabolic acidosis due to vancomycin-resistant enterococci (VRE) infection, and elevated D-lactic acid. Copyright © 2014 Elsevier B.V. All rights reserved.

Successful left hemihepatectomy and perioperative management of a patient with biliary cystadenocarcinoma, complicated with MELAS syndrome: report of a case.

PubMed

Ohno, Ayami; Mori, Akira; Doi, Ryuichiro; Yonenaga, Yoshikuni; Asano, Noboru; Uemoto, Shinji

2010-09-01

Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like syndrome (MELAS) is a rare, fetal disease caused by a mutation in mitochondrial DNA that leads to impaired oxidative metabolism in skeletal muscle, the central nervous system, and liver function. This report presents the case of a 50-year-old woman with biliary cystadenocarcinoma complicated by MELAS who underwent a successful left hemihepatectomy. In this case, the diagnostic key for the malignant tumor was an (18)F-fluorodeoxyglucose positron emission tomography study, which was useful even in a patient with MELAS, which causes abnormal glucose metabolism. The perioperative management of such patients includes special precautions to prevent lactic acidosis and deterioration of the reserved liver function after a hepatectomy, since the mitochondrial function in MELAS patients is abnormal. The patient in this report has remained free of liver dysfunctions and cancer recurrence for 2 years following the hepatectomy. This is the first report of a successful major hepatectomy for a patient with MELAS.

The kidney of chicken adapts to chronic metabolic acidosis: in vivo and in vitro studies.

PubMed

Craan, A G; Lemieux, G; Vinay, P; Gougoux, A

1982-08-01

Renal adaptation to chronic metabolic acidosis was studies in Arbor Acre hens receiving ammonium chloride by stomach tube 0.75 g/kg/day during 6 days. During a 14-day study, it was shown that the animals could excrete as much as 60% of the acid load during ammonium chloride administration. At the same time urate excretion fell markedly but the renal contribution to urate excretion (14%) did not change. During acidosis, blood glutamine increased twofold and the tissue concentration of glutamine rose in both liver and kidney. Infusion of L-glutamine led to increased ammonia excretion and more so in acidotic animals. Glutaminase I, glutamate dehydrogenase, alanine aminotransferase (GPT), and malic enzyme activities increased in the kidney during acidosis but phosphoenolpyruvate carboxykinase (PEPCK) activity did not change. Glutaminase I was not found in the liver, but hepatic glutamine synthetase rose markedly during acidosis. Glutamine synthetase was not found in the kidney. Renal tubules incubated with glutamine and alanine were ammoniagenic and gluconeogenic to the same degree as rat tubules with the same increments in acidosis. Lactate was gluconeogenic without increment during acidosis. The present study indicates that the avian kidney adapts to chronic metabolic acidosis with similarities and differences when compared to dog and rat. Glutamine originating from the liver appears to be the major ammoniagenic substrate. Our data also support the hypothesis that hepatic urate synthesis is decreased during acidosis.

Acidosis

MedlinePlus

... Respiratory acidosis develops when there is too much carbon dioxide (an acid) in the body. This type ... when the body is unable to remove enough carbon dioxide through breathing. Other names for respiratory acidosis ...

Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis

PubMed Central

Adeva-Andany, María M.; Fernández-Fernández, Carlos; Mouriño-Bayolo, David; Castro-Quintela, Elvira; Domínguez-Montero, Alberto

2014-01-01

Metabolic acidosis occurs when a relative accumulation of plasma anions in excess of cations reduces plasma pH. Replacement of sodium bicarbonate to patients with sodium bicarbonate loss due to diarrhea or renal proximal tubular acidosis is useful, but there is no definite evidence that sodium bicarbonate administration to patients with acute metabolic acidosis, including diabetic ketoacidosis, lactic acidosis, septic shock, intraoperative metabolic acidosis, or cardiac arrest, is beneficial regarding clinical outcomes or mortality rate. Patients with advanced chronic kidney disease usually show metabolic acidosis due to increased unmeasured anions and hyperchloremia. It has been suggested that metabolic acidosis might have a negative impact on progression of kidney dysfunction and that sodium bicarbonate administration might attenuate this effect, but further evaluation is required to validate such a renoprotective strategy. Sodium bicarbonate is the predominant buffer used in dialysis fluids and patients on maintenance dialysis are subjected to a load of sodium bicarbonate during the sessions, suffering a transient metabolic alkalosis of variable severity. Side effects associated with sodium bicarbonate therapy include hypercapnia, hypokalemia, ionized hypocalcemia, and QTc interval prolongation. The potential impact of regular sodium bicarbonate therapy on worsening vascular calcifications in patients with chronic kidney disease has been insufficiently investigated. PMID:25405229

Central pontine myelinolysis: a rare presentation secondary to hyperglycaemia.

PubMed

Saini, Monica; Mamauag, Marlie Jane; Singh, Rajinder

2015-04-01

Central pontine myelinolysis (CPM) is classically described as a demyelinating condition that results from the rapid correction of hyponatraemia. CPM has also been reported to arise from hyperglycaemia in association with concomitant acidosis, hypernatraemia and hyperosmolar syndrome. Herein, we report a rare presentation of CPM, which was purely secondary to hyperosmolar hyperglycaemia. The patient presented with ataxia and pseudobulbar affect, which evolved subacutely over a duration of two weeks. It is important to note that, in addition to acute changes in osmolality, a subacute shift secondary to hyperglycaemia may also lead to CPM.

Renal Tubular Acidosis in Patients with Primary Sjögren's Syndrome.

PubMed

Jung, Su Woong; Park, Eun Ji; Kim, Jin Sug; Lee, Tae Won; Ihm, Chun Gyoo; Lee, Sang Ho; Moon, Ju-Young; Kim, Yang Gyun; Jeong, Kyung Hwan

2017-09-01

Primary Sjögren's syndrome (pSS) is characterized by lymphocytic infiltration of the exocrine glands resulting in decreased saliva and tear production. It uncommonly involves the kidneys in various forms, including tubulointerstitial nephritis, renal tubular acidosis, Fanconi syndrome, and rarely glomerulonephritis. Its clinical symptoms include muscle weakness, periodic paralysis, and bone pain due to metabolic acidosis and electrolyte imbalance. Herein, we describe the cases of two women with pSS whose presenting symptoms involve the kidneys. They had hypokalemia and normal anion gap metabolic acidosis due to distal renal tubular acidosis and positive anti-SS-A and anti-SS-B autoantibodies. Since one of them experienced femoral fracture due to osteomalacia secondary to renal tubular acidosis, an earlier diagnosis of pSS is important in preventing serious complications.

Recurrent Pyroglutamic Acidosis Related to Therapeutic Acetaminophen.

PubMed

Alhourani, Hazem M; Kumar, Aneel; George, Lekha K; Sarwar, Tahira; Wall, Barry M

2018-04-01

Pyroglutamic acid, an intermediate in glutathione metabolism, can lead to elevated anion gap metabolic acidosis as rare complication of acetaminophen therapy in adults. Acquired pyroglutamic acidosis has been observed primarily in settings associated with glutathione deficiency. Risk factors for glutathione deficiency include critical illness, chronic liver or kidney disease, advanced age, female gender, alcohol abuse, malnutrition, pregnancy, antiepileptic drugs, and chronic acetaminophen use. Diagnosis of pyroglutamic acidosis requires both the exclusion of common etiologies of increased anion gap metabolic acidosis and a high index of suspicion. Treatment involves discontinuation of acetaminophen, supportive care, and addressing risk factors for glutathione deficiency. The current report describes an ambulatory patient with multiple risk factors for glutathione deficiency, who developed recurrent pyroglutamic acidosis due to acetaminophen use with therapeutic blood levels of acetaminophen. Published by Elsevier Inc.

Phenformin and lactic acidosis: a case report and review.

PubMed

Kwong, S C; Brubacher, J

1998-01-01

Phenformin was removed from the U.S. market 20 years ago because of a high incidence of lactic acidosis. Unfortunately, this medication is still available from foreign sources. Another biguanide, metformin, was reintroduced to the United States market for the treatment of diabetes. Biguanide-induced lactic acidosis should be included in the differential diagnosis of elevated anion gap metabolic acidosis. We present a case of phenformin-induced lactic acidosis in which we were consulted at the local poison control center. We also review its pathophysiology, presentation, and treatment. A review of the actions of phenformin illustrates the mechanism of pathology that may also occur with metformin. Risk factors for the development of lactic acidosis include renal deficiency, hepatic disease, cardiac disease, and drug interaction such as cimetidine.

Effect of air breathing on acid-base and ion regulation after exhaustive exercise and during low pH exposure in the bowfin, Amia calva.

PubMed

Gonzalez, R J; Milligan, L; Pagnotta, A; McDonald, D G

2001-01-01

To explore a potential conflict between air breathing and acid-base regulation in the bowfin (Amia calva), we examined how individuals with access to air differed from fish without air access in their response to acidosis. After exhaustive exercise, bowfin with access to air recovered significantly more slowly from the acidosis than fish without air access. While arterial blood pH (pH(a)) of fish without air access recovered to resting levels by 8 h, pH(a) was still significantly depressed in fish having access to air. In addition, Pco(2) was slightly more elevated in fish having air access than those without it. Fish with access to air still had a significant metabolic acid load after 8-h recovery, while those without air access completely cleared the load within 4 h. These results suggest that bowfin with access to air were breathing air and, consequently, were less able to excrete CO(2) and H(+) and experienced a delayed recovery. In contrast, during exposure to low pH, air breathing seemed to have a protective effect on acid-base status in bowfin. During exposure to low pH water, bowfin with access to air developed a much milder acidosis than bowfin without air access. The more severe acidosis in fish without air access was caused by an increased rate of lactic acid production. It appears that enhanced O(2) delivery allowed air-breathing bowfin to avoid acidosis-induced anaerobic metabolism and lactic acid production. In addition, during low pH exposure, plasma Na(+) and Cl(-) concentrations of fish without air access fell slightly more rapidly than those in fish with air access, indicating that the branchial ventilatory changes associated with air breathing limited, to some degree, ion losses associated with low pH exposure.

Sympathetic activation in exercise is not dependent on muscle acidosis. Direct evidence from studies in metabolic myopathies

NASA Technical Reports Server (NTRS)

Vissing, J.; Vissing, S. F.; MacLean, D. A.; Saltin, B.; Quistorff, B.; Haller, R. G.; Blomqvist, C. G. (Principal Investigator)

1998-01-01

Muscle acidosis has been implicated as a major determinant of reflex sympathetic activation during exercise. To test this hypothesis we studied sympathetic exercise responses in metabolic myopathies in which muscle acidosis is impaired or augmented during exercise. As an index of reflex sympathetic activation to muscle, microneurographic measurements of muscle sympathetic nerve activity (MSNA) were obtained from the peroneal nerve. MSNA was measured during static handgrip exercise at 30% of maximal voluntary contraction force to exhaustion in patients in whom exercise-induced muscle acidosis is absent (seven myophosphorylase deficient patients; MD [McArdle's disease], and one patient with muscle phosphofructokinase deficiency [PFKD]), augmented (one patient with mitochondrial myopathy [MM]), or normal (five healthy controls). Muscle pH was monitored by 31P-magnetic resonance spectroscopy during handgrip exercise in the five control subjects, four MD patients, and the MM and PFKD patients. With handgrip to exhaustion, the increase in MSNA over baseline (bursts per minute [bpm] and total activity [%]) was not impaired in patients with MD (17+/-2 bpm, 124+/-42%) or PFKD (65 bpm, 307%), and was not enhanced in the MM patient (24 bpm, 131%) compared with controls (17+/-4 bpm, 115+/-17%). Post-handgrip ischemia studied in one McArdle patient, caused sustained elevation of MSNA above basal suggesting a chemoreflex activation of MSNA. Handgrip exercise elicited an enhanced drop in muscle pH of 0.51 U in the MM patient compared with the decrease in controls of 0.13+/-0.02 U. In contrast, muscle pH increased with exercise in MD by 0.12+/-0.05 U and in PFKD by 0.01 U. In conclusion, patients with glycogenolytic, glycolytic, and oxidative phosphorylation defects show normal muscle sympathetic nerve responses to static exercise. These findings indicate that muscle acidosis is not a prerequisite for sympathetic activation in exercise.

Clinical and biochemical findings in Mexican patients with distal renal tubular acidosis.

PubMed

Guerra-Hernández, Norma; Matos-Martínez, Mario; Ordaz-López, Karen Verónica; Camargo-Muñiz, María Dolores; Medeiros, Mara; Escobar-Pérez, Laura

2014-01-01

Renal tubular acidosis (RTA) is a rare disease characterized by a normal serum anion gap, sustained metabolic acidosis, low concentration of plasma bicarbonate, variable hyperchloremia and hypokalemia and conserved glomerular filtration rate. RTA is developed during the first year of life and produces failure to thrive and anorexia. Primary distal RTA (type 1) is a renal syndrome with a reduced ability to excrete the acid load through the collecting ducts and impairment to concentrate the urine causing polyuria and dehydration. Evaluate the current health status and describe the clinical findings and progress of Mexican patients with distal RTA. Demonstrate the distal urinary acidification defect by measuring the urinary pCO2 tension in alkaline urines. We looked for infants in tertiary care hospitals with a clinical history of normal serum anion gap, metabolic acidosis, hypokalemia, hyperchloremia, nephrocalcinosis, sensorineural hearing loss and inability for urine acidification under systemic metabolic acidosis. Biochemical analysis were performed periodically. Alkali medication was not suspended in one patient to assess urinary acidification with oral administration of sodium bicarbonate (2 mEq/Kg) and acetazolamide (500 mg/1.73 m2 body surface). Urinary pCO2 levels were determined at 60 and 90 min. Three children, one adolescent and one adult with distal RTA were found. They had an infant history of dehydration, failure to thrive, anorexia, vomiting, muscle paralysis, hypercalciuria, urinary infections, polyuria, polydipsia and polyhidramnios during pregnancy. Severe nephrocalcinosis was detected in all patients whereas sensorineural hearing loss was developed in four cases. Under the alkali medication all cases but one were normocalciuric. A patient developed kidney failure. The urinary acidification test confirmed the innability to eliminate the acid load. Early diagnosis in infancy and continuos alkali medication were of great benefit for most of the patients. Urinary pCO2 levels in alkaline urine provided an index for collecting duct hydrogen-ion secretion. To our knowledge this is the first report of mexican patients with distal RTA.

Citrate metabolism and its complications in non-massive blood transfusions: association with decompensated metabolic alkalosis+respiratory acidosis and serum electrolyte levels.

PubMed

Bıçakçı, Zafer; Olcay, Lale

2014-06-01

Metabolic alkalosis, which is a non-massive blood transfusion complication, is not reported in the literature although metabolic alkalosis dependent on citrate metabolism is reported to be a massive blood transfusion complication. The aim of this study was to investigate the effect of elevated carbon dioxide production due to citrate metabolism and serum electrolyte imbalance in patients who received frequent non-massive blood transfusions. Fifteen inpatients who were diagnosed with different conditions and who received frequent blood transfusions (10-30 ml/kg/day) were prospectively evaluated. Patients who had initial metabolic alkalosis (bicarbonate>26 mmol/l), who needed at least one intensive blood transfusion in one-to-three days for a period of at least 15 days, and whose total transfusion amount did not fit the massive blood transfusion definition (<80 ml/kg) were included in the study. The estimated mean total citrate administered via blood and blood products was calculated as 43.2 ± 34.19 mg/kg/day (a total of 647.70 mg/kg in 15 days). Decompensated metabolic alkalosis+respiratory acidosis developed as a result of citrate metabolism. There was a positive correlation between cumulative amount of citrate and the use of fresh frozen plasma, venous blood pH, ionized calcium, serum-blood gas sodium and mortality, whereas there was a negative correlation between cumulative amount of citrate and serum calcium levels, serum phosphorus levels and amount of urine chloride. In non-massive, but frequent blood transfusions, elevated carbon dioxide production due to citrate metabolism causes intracellular acidosis. As a result of intracellular acidosis compensation, decompensated metabolic alkalosis+respiratory acidosis and electrolyte imbalance may develop. This situation may contribute to the increase in mortality. In conclusion, it should be noted that non-massive, but frequent blood transfusions may result in certain complications. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical Predictors and Outcome of Metabolic Acidosis in Under-Five Children Admitted to an Urban Hospital in Bangladesh with Diarrhea and Pneumonia

PubMed Central

Chisti, Mohammod J.; Ahmed, Tahmeed; Ashraf, Hasan; Faruque, A. S. G.; Bardhan, Pradip K.; Dey, Sanjoy Kumer; Huq, Sayeeda; Das, Sumon Kumar; Salam, Mohammed A.

2012-01-01

Background Clinical features of metabolic acidosis and pneumonia frequently overlap in young diarrheal children, resulting in differentiation from each other very difficult. However, there is no published data on the predictors of metabolic acidosis in diarrheal children also having pneumonia. Our objective was to evaluate clinical predictors of metabolic acidosis in under-five diarrheal children with radiological pneumonia, and their outcome. Methods We prospectively enrolled all under-five children (n = 164) admitted to the Special Care Ward (SCW) of the Dhaka Hospital of icddr, b between September and December 2007 with diarrhea and radiological pneumonia who also had their total serum carbon-dioxide estimated. We compared the clinical features and outcome of children with radiological pneumonia and diarrhea with (n = 98) and without metabolic acidosis (n = 66). Results Children with metabolic acidosis more often had higher case-fatality (16% vs. 5%, p = 0.039) compared to those without metabolic acidosis on admission. In logistic regression analysis, after adjusting for potential confounders such as age of the patient, fever on admission, and severe wasting, the independent predictors of metabolic acidosis in under-five diarrheal children having pneumonia were clinical dehydration (OR 3.57, 95% CI 1.62–7.89, p = 0.002), and low systolic blood pressure even after full rehydration (OR 1.02, 95% CI 1.01–1.04, p = 0.005). Proportions of children with cough, respiratory rate/minute, lower chest wall indrawing, nasal flaring, head nodding, grunting respiration, and cyanosis were comparable (p>0.05) among the groups. Conclusion and Significance Under-five diarrheal children with radiological pneumonia having metabolic acidosis had frequent fatal outcome than those without acidosis. Clinical dehydration and persistent systolic hypotension even after adequate rehydration were independent clinical predictors of metabolic acidosis among the children. However, metabolic acidosis in young diarrheal children had no impact on the diagnostic clinical features of radiological pneumonia which underscores the importance of early initiation of appropriate antibiotics to combat morbidity and deaths in such population. PMID:22720060

An East Asian Common Variant Vinculin P.Asp841His Was Associated With Sudden Unexplained Nocturnal Death Syndrome in the Chinese Han Population.

PubMed

Cheng, Jianding; Kyle, John W; Lang, Di; Wiedmeyer, Brandi; Guo, Jian; Yin, Kun; Huang, Lei; Vaidyanathan, Ravi; Su, Terry; Makielski, Jonathan C

2017-04-03

We have identified the cardiomyopathy-susceptibility gene vinculin ( VCL ) mutation M94I may account for a sudden unexplained nocturnal death syndrome (SUNDS) case. We addressed whether VCL common variant D841H is associated with SUNDS. In 8 of 120 SUNDS cases, we detected an East Asian common VCL variant p.Asp841His (D841H). Comparing the H841 allele frequency of the general population in the local database (15 of 1818) with SUNDS victims (10 of 240) gives an odds ratio for SUNDS of 5.226 (95% CI, 2.321, 11.769). The VCL-D841H variant was engineered and either coexpressed with cardiac sodium channel (SCN5A) in HEK293 cells or overexpressed in human induced pluripotent stem-cell-derived cardiomyocytes to examine its effects on sodium channel function using the whole-cell patch-clamp method. In HEK293 cells, under physiological pH conditions (pH 7.4), D841H caused a 29% decrease in peak I N a amplitude compared to wild type (WT), whereas under acidotic conditions (pH 7.0), D841H decreased further to 43% along with significant negative shift in inactivation compared to WT at pH 7.4. In induced pluripotent stem-cell-derived cardiomyocytes, similar effects of D841H on I N a were observed. VCL colocalized with SCN5A at the intercalated disk in human cardiomyocytes. VCL was also confirmed to directly interact with SCN5A, and VCL-D841H did not disrupt the association of VCL and SCN5A. A VCL common variant was genetically and biophysically associated with Chinese SUNDS. The aggravation of loss of function of SCN5A caused by VCL-D841H under acidosis supports that nocturnal sleep respiratory disorders with acidosis may play a key role in the pathogenesis of SUNDS. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Effects of hypercapnia and NO synthase inhibition in sustained hypoxic pulmonary vasoconstriction

PubMed Central

2012-01-01

Background Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange during local acute (0-30 min), as well as sustained (> 30 min) hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined. Method We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate), and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min) and endothelial permeability. Results In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-NG-Nitroarginine (L-NNA), a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS), decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc). This increase disappeared after administration of 1400 W. Conclusion Hypercapnia with and without acidosis increased HPV during conditions of sustained hypoxia. The increase of sustained HPV and endothelial permeability in hypoxic hypercapnia without acidosis was iNOS dependent. PMID:22292558

Effects of intravenous hyperosmotic sodium bicarbonate on arterial and cerebrospinal fluid acid-base status and cardiovascular function in calves with experimentally induced respiratory and strong ion acidosis.

PubMed

Berchtold, Joachim F; Constable, Peter D; Smith, Geoffrey W; Mathur, Sheerin M; Morin, Dawn E; Tranquilli, William J

2005-01-01

The objectives of this study were to determine the effects of hyperosmotic sodium bicarbonate (HSB) administration on arterial and cerebrospinal fluid (CSF) acid-base balance and cardiovascular function in calves with experimentally induced respiratory and strong ion (metabolic) acidosis. Ten healthy male Holstein calves (30-47 kg body weight) were instrumented under halothane anesthesia to permit cardiovascular monitoring and collection of blood samples and CSE Respiratory acidosis was induced by allowing the calves to spontaneously ventilate, and strong ion acidosis was subsequently induced by i.v. administration of L-lactic acid. Calves were then randomly assigned to receive either HSB (8.4% NaHCO3; 5 ml/kg over 5 minutes, i.v.; n=5) or no treatment (controls, n=5) and monitored for 1 hour. Mixed respiratory and strong ion acidosis was accompanied by increased heart rate, cardiac index, mean arterial pressure, cardiac contractility (maximal rate of change of left ventricular pressure), and mean pulmonary artery pressure. Rapid administration of HSB immediately corrected the strong ion acidosis, transiently increased arterial partial pressure of carbon dioxide (P(CO2)), and expanded the plasma volume. The transient increase in arterial P(CO2) did not alter CSF P(CO2) or induce paradoxical CSF acidosis. Compared to untreated control calves, HSB-treated calves had higher cardiac index and contractility and a faster rate of left ventricular relaxation for 1 hour after treatment, indicating that HSB administration improved myocardial systolic function. We conclude that rapid i.v. administration of HSB provided an effective and safe method for treating strong ion acidosis in normovolemic halothane-anesthetized calves with experimentally induced respiratory and strong ion acidosis. Fear of inducing paradoxical CSF acidosis is not a valid reason for withholding HSB administration in calves with mixed respiratory and strong ion acidosis.

Effects and Mechanisms by Which Hypercapnic Acidosis Inhibits Sepsis-Induced Canonical Nuclear Factor-κB Signaling in the Lung.

PubMed

Masterson, Claire; O'Toole, Daniel; Leo, Annemarie; McHale, Patricia; Horie, Shahd; Devaney, James; Laffey, John G

2016-04-01

Diverse effects of hypercapnic acidosis are mediated via inhibition of nuclear factor-κB, a pivotal transcription factor, in the setting of injury, inflammation, and repair, but the underlying mechanisms of action of hypercapnic acidosis on this pathway is unclear. We aim to examine the effect of hypercapnic acidosis on the nuclear factor-κB pathway in the setting of Escherichia coli-induced lung injury and characterize the underlying mechanisms in subsequent in vitro studies. In vivo animal study and subsequent in vitro studies. University Research Laboratory. Adult male Sprague-Dawley rats and pulmonary epithelial cells. Following pulmonary IκBα-SuperRepressor transgene overexpression or sham and intratracheal E. coli inoculation, rats underwent 4 hours of mechanical ventilation under normocapnia or hypercapnic acidosis, and nuclear factor-κB activation, animal survival, lung injury, and cytokine profile were assessed. Subsequent in vitro studies examined the effect of hypercapnic acidosis on specific nuclear factor-κB canonical pathway kinases via overexpression of these components and in vitro kinase activity assays. The effect of hypercapnic acidosis on the p50/p65 nuclear factor-κB heterodimer was then assessed. Hypercapnic acidosis and IκBα-SuperRepressor transgene overexpression reduced E. coli-induced lung inflammation and injury, decreased nuclear factor-κB activity, and increased animal survival. Hypercapnic acidosis inhibited canonical nuclear factor-κB signaling via reduced phosphorylative activation, reducing IκB kinase-β activation and intrinsic activity, thereby decreasing IκBα degradation, and subsequent nuclear factor-κB translocation. Hypercapnic acidosis also directly reduced DNA binding of the nuclear factor-κB p65 subunit, although this effect was less marked. Hypercapnic acidosis reduced E. coli inflammation and lung injury in vivo and reduced nuclear factor-κB activation predominantly by inhibiting the activation and intrinsic activity of IκB kinase-β.

Recurrent lactic acidosis and hypoglycemia with inadvertent metformin use: a case of look-alike pills.

PubMed

Jacob, Tess; Garrick, Renee; Goldberg, Michael D

2018-01-01

Metformin is recommended as the first-line agent for the treatment of type 2 diabetes. Although this drug has a generally good safety profile, rare but potentially serious adverse effects may occur. Metformin-associated lactic acidosis, although very uncommon, carries a significant risk of mortality. The relationship between metformin accumulation and lactic acidosis is complex and is affected by the presence of comorbid conditions such as renal and hepatic disease. Plasma metformin levels do not reliably correlate with the severity of lactic acidosis. We present a case of inadvertent metformin overdose in a patient with both renal failure and hepatic cirrhosis, leading to two episodes of lactic acidosis and hypoglycemia. The patient was successfully treated with hemodialysis both times and did not develop any further lactic acidosis or hypoglycemia, after the identification of metformin tablets accidentally mixed in with his supply of sevelamer tablets. Early initiation of renal replacement therapy is key in decreasing lactic acidosis-associated mortality. When a toxic ingestion is suspected, direct visualization of the patient's pills is advised in order to rule out the possibility of patient- or pharmacist-related medication errors.Though sending a specimen for determination of the plasma metformin concentration is important when a metformin-treated patient with diabetes presents with lactic acidosis, complex relationships exist between metformin accumulation, hyperlactatemia and acidosis, and the drug may not always be the precipitating factor.Intermittent hemodialysis is recommended as the first-line treatment for metformin-associated lactic acidosis (MALA).An investigational delayed-release form of metformin with reduced systemic absorption may carry a lower risk for MALA in patients with renal insufficiency, in whom metformin therapy may presently be contraindicated.

Association between Metformin Use and Risk of Lactic Acidosis or Elevated Lactate Concentration in Type 2 Diabetes.

PubMed

Lee, Eun Young; Hwang, Sena; Lee, Yong Ho; Lee, Seo Hee; Lee, Young Mi; Kang, Hua Pyong; Han, Eugene; Lee, Woonhyoung; Lee, Byung Wan; Kang, Eun Seok; Cha, Bong Soo; Lee, Hyun Chul

2017-03-01

Metformin can reduce diabetes-related complications and mortality. However, its use is limited because of potential lactic acidosis-associated adverse effects, particularly in renal impairment patients. We aimed to investigate the association of metformin use with lactic acidosis and hyperlactatemia in patients with type 2 diabetes. This was a cross-sectional study from a tertiary university-affiliated medical center. A total of 1954 type 2 diabetes patients were recruited in 2007-2011, and stratified according to the estimated glomerular filtration rate of 60 mL/min/1.73 m². Lactic acidosis was defined as plasma lactate levels >5 mmol/L and arterial pH <7.35. Metformin was used in 61.4% of the patients with type 2 diabetes mellitus. Plasma lactate levels were not different in the patients with and without metformin use. There was no difference in prevalence of hyperlactatemia and lactic acidosis between the patients with and without metformin use (18.9% vs. 18.7%, p=0.905 for hyperlactatemia and 2.8% vs. 3.3%, p=0.544 for lactic acidosis). Similar results were observed in the patients with estimated glomerular filtration rate <60 mL/min/1.73 m². Most patients with lactic acidosis had at least one condition related to hypoxia or poor tissue perfusion. Multiple regression analysis indicated no association between metformin use and lactic acidosis, whereas tissue hypoxia was an independent risk factor for lactic acidosis [odds ratio 4.603 (95% confidence interval, 1.327-15.965)]. Metformin use was not associated with hyperlactatemia or lactic acidosis in patients with type 2 diabetes.

Risk of lactic acidosis in type 2 diabetes patients using metformin: A case control study.

PubMed

Aharaz, Abdellatif; Pottegård, Anton; Henriksen, Daniel Pilsgaard; Hallas, Jesper; Beck-Nielsen, Henning; Lassen, Annmarie Touborg

2018-01-01

Metformin constitutes first-line treatment of type 2 diabetes mellitus. It is presumed to have lactic acidosis as a dangerous, but rare, side effect. To estimate the incidence rate of lactic acidosis in patients with type 2 diabetes mellitus as well as to estimate the relative risk of lactic acidosis associated with metformin treatment. This is a population-based combined cohort and case-control study among patients with type 2 diabetes mellitus who were acutely admitted with lactic acidosis at Odense University Hospital, Denmark; in the period from 1st June 2009 to 1st October 2013. The patients included as cases were all acutely hospitalized with lactic acidosis (pH <7.35 and lactate ≥2.0 mmol/l). For each case, we identified 24 age- and sex-matched controls sampled from the same cohort with type 2 diabetes mellitus. The use of metformin identified by using a prescription database. Analyses included multivariable logistic regression and adjusting for predefined confounding: renal function, HbA1c, comorbidity and diabetes duration. Our cohort included 10,652 patients with type 2 diabetes mellitus with a median age of 74 years, and 51.5% were male. During follow-up, 163 individuals were hospitalized with lactic acidosis, corresponding to an incidence rate of 391/100,000 person years. Use of metformin was not associated with lactic acidosis: adjusted odds ratio was 0.79 (95%CI 0.54-1.17). Among patients with type 2 diabetes mellitus, the incidence rate of acute hospitalization with lactic acidosis was 391/100,000 person years. Use of metformin did not increase the risk of lactic acidosis. However, comorbidity seems to be an important risk factor.

Comparative analysis of lactic acidosis induced by linezolid and vancomycin therapy using cohort and case-control studies of incidence and associated risk factors.

PubMed

Mori, Nobuaki; Kamimura, Yoshio; Kimura, Yuki; Hirose, Shoko; Aoki, Yasuko; Bito, Seiji

2018-04-01

Lactic acidosis is a rare complication of linezolid (LZD) therapy, and its incidence and risk factors remain unknown. This study aimed to compare the incidence of LZD-associated lactic acidosis (LALA) and vancomycin (VAN)-associated lactic acidosis (VALA) and investigate the risk factors for LALA. We performed a retrospective cohort study using propensity score-matched analyses comparing the incidence of lactic acidosis between LZD and VAN therapy. We included adult patients administered LZD or VAN between April 2014 and March 2016 and extracted patient baseline data. In a case-control study, we identified the risk factors of lactic acidosis in patients treated with LZD. We identified 94 and 313 patients who were administered LZD and VAN, respectively. The incidence of lactic acidosis after LZD and VAN therapy was 10.6 and 0.3%, respectively. After propensity score-matched analyses, the incidence of lactic acidosis with LZD therapy was significantly higher than that with VAN therapy [10.0% (8/80) vs. 0% (0/80), respectively; risk difference, 0.1; 95% confidence interval (CI), 0.03-0.17; p = 0.004]. In a case-control study, 10 patients with LALA were matched to 20 non-lactic acidosis patients by age and sex. Patients with LALA were more likely to have renal insufficiency than non-lactic acidosis patients that were in the univariate analysis (odds ratio, 7.4; 95% CI, 1.0-84.4; p = 0.02). This study indicates that LALA occurs more frequently than VALA does and is associated with renal insufficiency. Therefore, close monitoring of kidney function and serum lactate is recommended during LZD therapy.

Ruminal acidosis in feedlot: from aetiology to prevention.

PubMed

Hernández, Joaquín; Benedito, José Luis; Abuelo, Angel; Castillo, Cristina

2014-01-01

Acute ruminal acidosis is a metabolic status defined by decreased blood pH and bicarbonate, caused by overproduction of ruminal D-lactate. It will appear when animals ingest excessive amount of nonstructural carbohydrates with low neutral detergent fiber. Animals will show ruminal hypotony/atony with hydrorumen and a typical parakeratosis-rumenitis liver abscess complex, associated with a plethora of systemic manifestations such as diarrhea and dehydration, liver abscesses, infections of the lung, the heart, and/or the kidney, and laminitis, as well as neurologic symptoms due to both cerebrocortical necrosis and the direct effect of D-lactate on neurons. In feedlots, warning signs include decrease in chewing activity, weight, and dry matter intake and increase in laminitis and diarrhea prevalence. The prognosis is quite variable. Treatment will be based on the control of systemic acidosis and dehydration. Prevention is the most important tool and will require normalization of ruminal pH and microbiota. Appropriate feeding strategies are essential and involve changing the dietary composition to increase neutral detergent fiber content and greater particle size and length. Appropriate grain processing can control the fermentation rate while additives such as prebiotics or probiotics can help to stabilize the ruminal environment. Immunization against producers of D-lactate is being explored.

Atypical antipsychotic (clozapine) self-poisoning in late pregnancy presenting with absent fetal heart rate variability without acidosis and delayed peristalsis in the newborn baby: a case report.

PubMed

Novikova, N; Chitnis, M; Linder, V; Hofmeyr, G J

2009-08-01

A case of an attempted suicide with atypical antipsychotic (clozapine) in late pregnancy is reported. Toxic effects of clozapine in the mother as well as in the fetus and newborn were observed. It should be remembered as a rare cause of unexplained loss of consciousness in pregnant women, a cause of abnormalities on fetal cardiotocogram as well as a cause of delayed peristalsis in a newborn baby.

Lactic acidosis occurring during phenformin therapy

PubMed Central

Tomkins, A. M.; Jones, R.; Bloom, Arnold

1972-01-01

A case of severe lactic acidosis is described in a diabetic taking phenformin who was otherwise healthy. Substitution of metformin for phenformin did not lead to a recurrence of the lactic acidosis. PMID:5049258

Metabolic acidosis as a risk factor for the development of acute kidney injury and hospital mortality.

PubMed

Hu, Jiachang; Wang, Yimei; Geng, Xuemei; Chen, Rongyi; Xu, Xialian; Zhang, Xiaoyan; Lin, Jing; Teng, Jie; Ding, Xiaoqiang

2017-05-01

Metabolic acidosis has been proved to be a risk factor for the progression of chronic kidney disease, but its relation to acute kidney injury (AKI) has not been investigated. In general, a diagnosis of metabolic acidosis is based on arterial blood gas (ABG) analysis, but the diagnostic role of carbon dioxide combining power (CO 2 CP) in the venous blood may also be valuable to non-respiratory patients. This retrospective study included all adult non-respiratory patients admitted consecutively to our hospital between October 01, 2014 and September 30, 2015. A total of 71,089 non-respiratory patients were included, and only 4,873 patients were evaluated by ABG analysis at admission. In patients with ABG, acidosis, metabolic acidosis, decreased HCO 3 - and hypocapnia at admission was associated with the development of AKI, while acidosis and hypocapnia were independent predictors of hospital mortality. Among non-respiratory patients, decreased CO 2 CP at admission was an independent risk factor for AKI and hospital mortality. ROC curves indicated that CO 2 CP was a reasonable biomarker to exclude metabolic acidosis, dual and triple acid-base disturbances. The effect sizes of decreased CO 2 CP on AKI and hospital mortality varied according to age and different underlying diseases. Metabolic acidosis is an independent risk factor for the development of AKI and hospital mortality. In non-respiratory patient, decreased CO 2 CP is also an independent contributor to AKI and mortality and can be used as an indicator of metabolic acidosis.

Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo.

PubMed

Palpant, Nathan J; D'Alecy, Louis G; Metzger, Joseph M

2009-05-01

Intracellular acidosis is a profound negative regulator of myocardial performance. We hypothesized that titrating myofilament calcium sensitivity by a single histidine substituted cardiac troponin I (A164H) would protect the whole animal physiological response to acidosis in vivo. To experimentally induce severe hypercapnic acidosis, mice were exposed to a 40% CO(2) challenge. By echocardiography, it was found that systolic function and ventricular geometry were maintained in cTnI A164H transgenic (Tg) mice. By contrast, non-Tg (Ntg) littermates experienced rapid and marked cardiac decompensation during this same challenge. For detailed hemodymanic assessment, Millar pressure-conductance catheterization was performed while animals were treated with a beta-blocker, esmolol, during a severe hypercapnic acidosis challenge. Survival and load-independent measures of contractility were significantly greater in Tg vs. Ntg mice. This assay showed that Ntg mice had 100% mortality within 5 min of acidosis. By contrast, systolic and diastolic function were protected in Tg mice during acidosis, and they had 100% survival. This study shows that, independent of any beta-adrenergic compensation, myofilament-based molecular manipulation of inotropy by histidine-modified troponin I maintains cardiac inotropic and lusitropic performance and markedly improves survival during severe acidosis in vivo.

A Novel Swine Model for Evaluation of Potential Intravascular Hemostatic Agents

DTIC Science & Technology

2007-06-01

bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine. Shock 24:145–152. 2. Bellamy RF. 1984. The causes of death in...WZ, Pusateri AE, Uscilowicz JM, Delgado AV, Holcomb JB. 2005. Independent contributions of hypothermia and acidosis to coagulopathy in swine. J

Control of rectal gland secretion by blood acid-base status in the intact dogfish shark (Squalus acanthias).

PubMed

Wood, Chris M; Munger, R Stephen; Thompson, Jill; Shuttleworth, Trevor J

2007-05-14

In order to address the possible role of blood acid-base status in controlling the rectal gland, dogfish were fitted with indwelling arterial catheters for blood sampling and rectal gland catheters for secretion collection. In intact, unanaesthetized animals, isosmotic volume loading with 500 mmol L-1 NaCl at a rate of 15 mL kg-1 h-1 produced a brisk, stable rectal gland secretion flow of about 4 mL kg-1 h-1. Secretion composition (500 mmol L-1 Na+ and Cl-; 5 mmol L-1 K+; <1 mmol L-1 Ca2+, Mg2+, SO(4)2-, or phosphate) was almost identical to that of the infusate with a pH of about 7.2, HCO3- mmol L-1<1 mmol L-1 and a PCO2 (1 Torr) close to PaCO2. Experimental treatments superimposed on the infusion caused the expected disturbances in systemic acid-base status: respiratory acidosis by exposure to high environmental PCO2, metabolic acidosis by infusion of HCl, and metabolic alkalosis by infusion of NaHCO3. Secretion flow decreased markedly with acidosis and increased with alkalosis, in a linear relationship with extracellular pH. Secretion composition did not change, apart from alterations in its acid-base status, and made negligible contribution to overall acid-base balance. An adaptive control of rectal gland secretion by systemic acid-base status is postulated-stimulation by the "alkaline tide" accompanying the volume load of feeding and inhibition by the metabolic acidosis accompanying the volume contraction of exercise.

Understanding lactic acidosis in paracetamol (acetaminophen) poisoning.

PubMed

Shah, Anoop D; Wood, David M; Dargan, Paul I

2011-01-01

Paracetamol (acetaminophen) is one of the most commonly taken drugs in overdose in many areas of the world, and the most common cause of acute liver failure in both the UK and USA. Paracetamol poisoning can result in lactic acidosis in two different scenarios. First, early in the course of poisoning and before the onset of hepatotoxicity in patients with massive ingestion; a lactic acidosis is usually associated with coma. Experimental evidence from studies in whole animals, perfused liver slices and cell cultures has shown that the toxic metabolite of paracetamol, N-acetyl-p-benzo-quinone imine, inhibits electron transfer in the mitochondrial respiratory chain and thus inhibits aerobic respiration. This occurs only at very high concentrations of paracetamol, and precedes cellular injury by several hours. The second scenario in which lactic acidosis can occur is later in the course of paracetamol poisoning as a consequence of established liver failure. In these patients lactate is elevated primarily because of reduced hepatic clearance, but in shocked patients there may also be a contribution of peripheral anaerobic respiration because of tissue hypoperfusion. In patients admitted to a liver unit with paracetamol hepatotoxicity, the post-resuscitation arterial lactate concentration has been shown to be a strong predictor of mortality, and is included in the modified King's College criteria for consideration of liver transplantation. We would therefore recommend that post-resuscitation lactate is measured in all patients with a severe paracetamol overdose resulting in either reduced conscious level or hepatic failure. © 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.

[Dietetic treatment with fructose in a 5-year-old girl with recurrent D-lactic acidosis].

PubMed

Travieso Suárez, Lourdes; Quijada Fraile, Pilar; Pedrón Giner, Consuelo

2018-03-01

D-lactic acidosis is an infrequent complication, mainly reported in patients with short bowel syndrome. It is characterized by recurrent episodes of encephalopathy with elevated serum D-lactic acid, usually associating metabolic acidosis. The presence of D-lactate-producing bacteria is necessary for the development of this complication. Other factors, such as the ingestion of large amounts of carbohydrates or reduced intestinal motility, contribute to D-lactic acidosis. We report a case of recurrent D-lactic acidosis in a 5-year-old girl with short bowel syndrome, due to a midgut volvulus. She initially received oral antibiotics in order to treat bacterial overgrowth, together with oral carbohydrates restriction. Nevertheless, recurrences did occur. Subsequently, 25% of the enteral nutrition was replaced for a formula containing fructose exclusively, while other fermentable sugars were restricted from the diet. After 16 years of follow up, further recurrences of D-lactic acidosis were not observed.

Serum ionized calcium in dogs with chronic renal failure and metabolic acidosis.

PubMed

Kogika, Marcia M; Lustoza, Marcio D; Notomi, Marcia K; Wirthl, Vera A B F; Mirandola, Regina M S; Hagiwara, Mitika K

2006-12-01

Chronic renal failure (CRF) is a common disease in dogs, and many metabolic disorders can be observed, including metabolic acidosis and calcium and phosphorus disturbances. Acidosis may change the ionized calcium (i-Ca) fraction, usually increasing its concentration. In this study we evaluated the influence of acidosis on the serum concentration of i-Ca in dogs with CRF and metabolic acidosis. Dogs were studied in 2 groups: group I (control group = 40 clinically normal dogs) and group II (25 dogs with CRF and metabolic acidosis). Serum i-Ca was measured by an ion-selective electrode method; other biochemical analytes were measured using routine methods. The i-Ca concentration was significantly lower in dogs in group II than in group I; 56% of the dogs in group II were hypocalcemic. Hypocalcemia was observed in only 8% of dogs in group II when based on total calcium (t-Ca) concentration. No correlation between pH and i-Ca concentration was observed. A slight but significant correlation was detected between i-Ca and serum phosphorus concentration (r = -.284; P = .022), as well as between serum t-Ca and i-Ca concentration (r = .497; P < .0001). The i-Ca concentration in dogs with CRF and metabolic acidosis varied widely from that of t-Ca, showing the importance of determining the biologically active form of calcium. Metabolic acidosis did not influence the increase in i-Ca concentration, so other factors besides acidosis in CRF might alter the i-Ca fraction, such as hyperphosphatemia and other compounds that may form complexes with calcium.

Tested Demonstrations.

ERIC Educational Resources Information Center

Gilbert, George L., Ed.

1983-01-01

Discusses a supplement to the "water to rose" demonstration in which a pink color is produced. Also discusses blood buffer demonstrations, including hydrolysis of sodium bicarbonate, simulated blood buffer, metabolic acidosis, natural compensation of metabolic acidosis, metabolic alkalosis, acidosis treatment, and alkalosis treatment. Procedures…

Life threatening hyperkalemia and acidosis secondary to trimethoprim-sulfamethoxazole treatment.

PubMed

Margassery, S; Bastani, B

2001-01-01

We present a 77-year-old male with moderate chronic renal insufficiency from diabetic nephropathy who developed severe metabolic acidosis and life threatening hyperkalemia on treatment with regular dose of trimethoprim-sulfamethoxazole (TMP-SMZ) for urinary tract infection. The metabolic acidosis and hyperkalemia resolved upon appropriate medical intervention and discontinuation of TMP-SMZ. While hyperkalemia has commonly been reported with high dose of TMP-SMZ, severe metabolic acidosis is quite uncommon with regular dose TMP-SMZ. We emphasize that patients with renal tubular acidosis (RTA), renal insufficiency, aldosterone deficiency, old age with reduced renal mass and function, and angiotensin converting enzyme (ACE)-inhibitor therapy are at high risk of developing these severe and potentially life threatening complications.

Acidosis in feedlot cattle.

PubMed

Nagaraja, T G; Lechtenberg, Kelly F

2007-07-01

Mortality from digestive diseases in feedlot cattle is second only to that from respiratory diseases. Acidosis is a major digestive disorder and is likely to continue because of ongoing attempts to improve the efficiency of beef production by feeding more grain and less roughage. Subacute acidosis is the most prevalent form of acidosis in feedlots but is difficult to diagnose because of the absence of overt clinical signs. Control of acidosis is achieved largely by sound nutritional management. No single strategy or solution exists; however, an effective management strategy should factor in dietary formulation, a consistent feeding program, prudent bunk management, use of nonstarch by-products, and feed additives to minimize pen-to-pen and animal-to-animal variations in feed intake.

Metabolic acidosis increases fibroblast growth factor 23 in neonatal mouse bone

PubMed Central

Culbertson, Christopher D.; Kyker-Snowman, Kelly; Bushinsky, David A.

2012-01-01

Fibroblast growth factor 23 (FGF23) significantly increases with declining renal function, leading to reduced renal tubular phosphate reabsorption, decreased 1,25-dihydroxyvitamin D, and increased left ventricular hypertrophy. Elevated FGF23 is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the mechanisms by which it is regulated are not clear. Patients with chronic kidney disease have decreased renal acid excretion leading to metabolic acidosis, which has a direct effect on bone cell activity. We hypothesized that metabolic acidosis would directly increase bone cell FGF23 production. Using cultured neonatal mouse calvariae, we found that metabolic acidosis increased medium FGF23 protein levels as well as FGF23 RNA expression at 24 h and 48 h compared with incubation in neutral pH medium. To exclude that the increased FGF23 was secondary to metabolic acidosis-induced release of bone mineral phosphate, we cultured primary calvarial osteoblasts. In these cells, metabolic acidosis increased FGF23 RNA expression at 6 h compared with incubation in neutral pH medium. Thus metabolic acidosis directly increases FGF23 mRNA and protein in mouse bone. If these results are confirmed in humans with chronic kidney disease, therapeutic interventions to mitigate acidosis, such as bicarbonate administration, may also lower levels of FGF23, decrease left ventricular hypertrophy, and perhaps even decrease mortality. PMID:22647635

Repeated ruminal acidosis challenges in lactating dairy cows at high and low risk for developing acidosis: feed sorting.

PubMed

Devries, T J; Dohme, F; Beauchemin, K A

2008-10-01

An experiment was conducted to determine whether the susceptibility of cows to ruminal acidosis influences feed sorting and whether feed sorting changes during a bout of ruminal acidosis. Eight ruminally cannulated cows were assigned to 1 of 2 acidosis risk levels: low risk (LR, mid-lactation cows fed a 60% forage diet) or high risk (HR, early lactation cows fed a 45% forage diet). As a result, diets were intentionally confounded with milk production to represent 2 different acidosis risk scenarios. Cows were exposed to an acidosis challenge in each of two 14-d periods. Each period consisted of 3 baseline days, a feed restriction day (restricting TMR to 50% of ad libitum intake), an acidosis challenge day (1-h meal of 4 kg of ground barley/wheat before allocating the TMR), and a recovery phase. Ruminal pH was measured continuously for the first 9 d of each period using an indwelling system. Feed and orts were sampled for 2 baseline days, on the challenge day, and 1 and 3 d after the challenge day for each cow and subjected to particle size analysis. The separator contained 3 screens (18, 9, and 1.18 mm) and a bottom pan to determine the proportion of long, medium, short, and fine particles, respectively. Sorting was calculated as the actual intake of each particle size fraction expressed as a percentage of the predicted intake of that fraction. All cows sorted against the longest and finest TMR particles and sorted for medium-length particles. Sorting was performed to a greater extent by the HR cows, and this sorting was related to low ruminal pH. Both HR and LR cows altered their sorting behavior in response to acidosis challenges. For the HR cows, severe acidosis was associated with increased sorting for the longer particles in the diet and against the shorter particles, likely to lessen the effects of the very.

Differences in baseline factors and survival between normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis in COPD exacerbation: A pilot study.

PubMed

Lun, Chung-Tat; Tsui, Miranda S N; Cheng, Suet-Lai; Chan, Veronica L; Leung, Wah-Shing; Cheung, Alice P S; Chu, Chung-Ming

2016-01-01

Patients with chronic obstructive pulmonary disease (COPD) experiencing acute exacerbation (AE-COPD) with decompensated respiratory acidosis are known to have poor outcomes in terms of recurrent respiratory failure and death. However, the outcomes of AE-COPD patients with compensated respiratory acidosis are not known. We performed a 1-year prospective, single-centre, cohort study in patients surviving the index admission for AE-COPD to compare baseline factors between groups with normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis. Survival analysis was done to examine time to readmissions, life-threatening events and death. A total of 250 patients fulfilling the inclusion and exclusion criteria were recruited and 245 patients were analysed. Compared with normocapnia, both compensated and decompensated respiratory acidosis are associated with lower FEV1 % (P < 0.001), higher GOLD stage (P = 0.003, <0.001) and higher BODE index (P = 0.038, 0.001) and a shorter time to life-threatening events (P < 0.001). Comparing compensated and decompensated respiratory acidosis, there was no difference in FEV1 (% predicted) (P = 0.15), GOLD stage (P = 0.091), BODE index (P = 0.158) or time to life-threatening events (P = 0.301). High PaCO2 level (P = 0.002) and previous use of non-invasive ventilation (NIV) in acute setting (P < 0.001) are predictive factors of future life-threatening events by multivariate analysis. Compared with normocapnia, both compensated and decompensated respiratory acidosis are associated with poorer lung function and higher risk of future life-threatening events. High PaCO2 level and past history of NIV use in acute settings were predictive factors for future life-threatening events. Compensated respiratory acidosis warrants special attention and optimization of medical therapy as it poses risk of life-threatening events. © 2015 Asian Pacific Society of Respirology.

Acidosis increases the susceptibility of respiratory epithelial cells to Pseudomonas aeruginosa-induced cytotoxicity.

PubMed

Torres, Iviana M; Demirdjian, Sally; Vargas, Jennifer; Goodale, Britton C; Berwin, Brent

2017-07-01

Bacterial infection can lead to acidosis of the local microenvironment, which is believed to exacerbate disease pathogenesis; however, the mechanisms by which changes in pH alter disease progression are poorly understood. We test the hypothesis that acidosis enhances respiratory epithelial cell death in response to infection with Pseudomonas aeruginosa Our findings support the idea that acidosis in the context of P. aeruginosa infection results in increased epithelial cell cytotoxicity due to ExoU intoxication. Importantly, enforced maintenance of neutral pH during P. aeruginosa infection demonstrates that cytotoxicity is dependent on the acidosis. Investigation of the underlying mechanisms revealed that host cell cytotoxicity correlated with increased bacterial survival during an acidic infection that was due to reduced bactericidal activity of host-derived antimicrobial peptides. These findings extend previous reports that the activities of antimicrobial peptides are pH-dependent and provide novel insights into the consequences of acidosis on infection-derived pathology. Therefore, this report provides the first evidence that physiological levels of acidosis increase the susceptibility of epithelial cells to acute Pseudomonas infection and demonstrates the benefit of maintaining pH homeostasis during a bacterial infection. Copyright © 2017 the American Physiological Society.

Cortical GABAergic neurons are more severely impaired by alkalosis than acidosis

PubMed Central

2013-01-01

Background Acid–base imbalance in various metabolic disturbances leads to human brain dysfunction. Compared with acidosis, the patients suffered from alkalosis demonstrate more severe neurological signs that are difficultly corrected. We hypothesize a causative process that the nerve cells in the brain are more vulnerable to alkalosis than acidosis. Methods The vulnerability of GABAergic neurons to alkalosis versus acidosis was compared by analyzing their functional changes in response to the extracellular high pH and low pH. The neuronal and synaptic functions were recorded by whole-cell recordings in the cortical slices. Results The elevation or attenuation of extracellular pH impaired these GABAergic neurons in terms of their capability to produce spikes, their responsiveness to excitatory synaptic inputs and their outputs via inhibitory synapses. Importantly, the dysfunction of these active properties appeared severer in alkalosis than acidosis. Conclusions The severer impairment of cortical GABAergic neurons in alkalosis patients leads to more critical neural excitotoxicity, so that alkalosis-induced brain dysfunction is difficultly corrected, compared to acidosis. The vulnerability of cortical GABAergic neurons to high pH is likely a basis of severe clinical outcomes in alkalosis versus acidosis. PMID:24314112

Postoperative Compensatory Ammonium Excretion Subsequent to Systemic Acidosis in Cardiac Patients.

PubMed

Roehrborn, Friederike; Dohle, Daniel-Sebastian; Waack, Indra N; Tsagakis, Konstantinos; Jakob, Heinz; Teloh, Johanna K

2017-01-01

Postoperative acid-base imbalances, usually acidosis, frequently occur after cardiac surgery. In most cases, the human body, not suffering from any severe preexisting illnesses regarding lung, liver, and kidney, is capable of transient compensation and final correction. The aim of this study was to correlate the appearance of postoperatively occurring acidosis with renal ammonium excretion. Between 07/2014 and 10/2014, a total of 25 consecutive patients scheduled for elective isolated coronary artery bypass grafting with cardiopulmonary bypass were enrolled in this prospective observational study. During the operative procedure and the first two postoperative days, blood gas analyses were carried out and urine samples collected. Urine samples were analyzed for the absolute amount of ammonium. Of all patients, thirteen patients developed acidosis as an initial disturbance in the postoperative period: five of respiratory and eight of metabolic origin. Four patients with respiratory acidosis but none of those with metabolic acidosis subsequently developed a base excess > +2 mEq/L. Ammonium excretion correlated with the increase in base excess. The acidosis origin seems to have a large influence on renal compensation in terms of ammonium excretion and the possibility of an overcorrection.

Postoperative Compensatory Ammonium Excretion Subsequent to Systemic Acidosis in Cardiac Patients

PubMed Central

Roehrborn, Friederike; Dohle, Daniel-Sebastian; Tsagakis, Konstantinos; Jakob, Heinz

2017-01-01

Background Postoperative acid-base imbalances, usually acidosis, frequently occur after cardiac surgery. In most cases, the human body, not suffering from any severe preexisting illnesses regarding lung, liver, and kidney, is capable of transient compensation and final correction. The aim of this study was to correlate the appearance of postoperatively occurring acidosis with renal ammonium excretion. Materials and Methods Between 07/2014 and 10/2014, a total of 25 consecutive patients scheduled for elective isolated coronary artery bypass grafting with cardiopulmonary bypass were enrolled in this prospective observational study. During the operative procedure and the first two postoperative days, blood gas analyses were carried out and urine samples collected. Urine samples were analyzed for the absolute amount of ammonium. Results Of all patients, thirteen patients developed acidosis as an initial disturbance in the postoperative period: five of respiratory and eight of metabolic origin. Four patients with respiratory acidosis but none of those with metabolic acidosis subsequently developed a base excess > +2 mEq/L. Conclusion Ammonium excretion correlated with the increase in base excess. The acidosis origin seems to have a large influence on renal compensation in terms of ammonium excretion and the possibility of an overcorrection. PMID:28612026

Is Lactate Production Related to Muscular Fatigue? A Pedagogical Proposition Using Empirical Facts

ERIC Educational Resources Information Center

Vaz Macedo, Denise; Lazarim, Fernanda Lorenzi; da Silva, Fernando Oliveira Catanho; Tessuti, Lucas Samuel; Hohl, Rodrigo

2009-01-01

The cause-effect relationship between lactic acid, acidosis, and muscle fatigue has been established in the literature. However, current experiments contradict this premise. Here, we describe an experiment developed by first-year university students planned to answer the following questions: 1) Which metabolic pathways of energy metabolism are…

Fluid and electrolyte disturbances in cirrhosis.

PubMed

Papper, S

1976-01-01

Glomerular filtration rate and renal plasma flow may be normal, reduced or increased in cirrhosis. The mechanism of departures from normal is not known. Other renal functional changes in cirrhosis include avid sodium reabsorption, impaired concentrating and diluting abilities, and partial renal tubular acidosis. Fluid and electrolyte disorders are common. Sodium retention with edema and ascites should generally be treated conservatively because they tend to disappear as the liver heals and because forced diuresis has hazards. The indications for diuretics are (1) incipient or overt atelectasis; (2) abdominal distress; and (3) possibility of skin breakdown. Hyponatremia is common and its mechanism and treatment must be assessed in each patient. Hypokalemia occurs and requires treatment. Respiratory alkalosis and renal tubular acidosis seldom need therapy. The hepatorenal syndrome is defined as functional renal failure in the absence of other known causes of renal functional impairment. The prognosis is terrible and therapy is unsatisfactory. The best approach is not to equate the occurrence of renal failure in cirrhosis with the hepatorenal syndrome. Rather the physician should first explore all treatable causes of renal failure, eg, dehydration, obstruction, infection, heart failure, potassium depletion, and others.

Biochemical testing in a laboratory tent and semi-intensive care of Ebola patients on-site in a remote part of Guinea: a paradigm shift based on a bleach-sensitive point-of-care device.

PubMed

Irenge, Leonid M; Dindart, Jean-Michel; Gala, Jean-Luc

2017-10-26

During the West Africa Ebola virus disease (EVD) outbreak, a Belgian laboratory was deployed for supporting the Ebola treatment unit (ETU) of N'Zerekore, Guinea. Besides diagnosis of EVD and malaria, biochemical parameters were tested and used to guide supportive treatment of EVD. To preserve analytes stability, lithium-heparin blood samples were analyzed using the i-STAT® point-of-care testing (POCT) handheld device without the viral inactivation step. To mitigate the risk of Ebola virus transmission, assays were performed inside a portable glovebox with strict biosafety procedures. Providing the medical staff with real-time biochemical data modified their therapeutic attitude, shifting from empiric to a semi-intensive laboratory-guided treatment of hydro-electrolytic disturbances, metabolic acidosis and/or impaired kidney function. As illustrated with representative EVD cases (n=8), optimized supportive treatment with intravenous fluid therapy and electrolyte replacement often helped correct these abnormalities. However, the harsh operating conditions, especially the use of bleach decontamination inside the glovebox, caused several technical failures and the final breakdown of the POCT device. POCT availability resulted in a paradigm shift in laboratory practice and care delivery at the N'Zerekore ETU. We conclude that there is urgent need for novel well-designed and validated POCT devices usable by non-expert operators in high ambient temperature and limited space. These devices should withstand regular and thorough decontamination by the personnel working on-site with life-threatening pathogens and be compatible with high biosafety level procedures. Such specific users' requirements need a European validation and standardization process of proposed solutions led by the EU Standardization Committee (CEN).

Responses of glomus cells to hypoxia and acidosis are uncoupled, reciprocal and linked to ASIC3 expression: selectivity of chemosensory transduction

PubMed Central

Lu, Yongjun; Whiteis, Carol A; Sluka, Kathleen A; Chapleau, Mark W; Abboud, François M

2013-01-01

Carotid body glomus cells are the primary sites of chemotransduction of hypoxaemia and acidosis in peripheral arterial chemoreceptors. They exhibit pronounced morphological heterogeneity. A quantitative assessment of their functional capacity to differentiate between these two major chemical signals has remained undefined. We tested the hypothesis that there is a differential sensory transduction of hypoxia and acidosis at the level of glomus cells. We measured cytoplasmic Ca2+ concentration in individual glomus cells, isolated in clusters from rat carotid bodies, in response to hypoxia ( mmHg) and to acidosis at pH 6.8. More than two-thirds (68%) were sensitive to both hypoxia and acidosis, 19% were exclusively sensitive to hypoxia and 13% exclusively sensitive to acidosis. Those sensitive to both revealed significant preferential sensitivity to either hypoxia or to acidosis. This uncoupling and reciprocity was recapitulated in a mouse model by altering the expression of the acid-sensing ion channel 3 (ASIC3) which we had identified earlier in glomus cells. Increased expression of ASIC3 in transgenic mice increased pH sensitivity while reducing cyanide sensitivity. Conversely, deletion of ASIC3 in the knockout mouse reduced pH sensitivity while the relative sensitivity to cyanide or to hypoxia was increased. In this work, we quantify functional differences among glomus cells and show reciprocal sensitivity to acidosis and hypoxia in most glomus cells. We speculate that this selective chemotransduction of glomus cells by either stimulus may result in the activation of different afferents that are preferentially more sensitive to either hypoxia or acidosis, and thus may evoke different and more specific autonomic adjustments to either stimulus. PMID:23165770

Central pontine myelinolysis: a rare presentation secondary to hyperglycaemia

PubMed Central

Saini, Monica; Mamauag, Marlie Jane; Singh, Rajinder

2015-01-01

Central pontine myelinolysis (CPM) is classically described as a demyelinating condition that results from the rapid correction of hyponatraemia. CPM has also been reported to arise from hyperglycaemia in association with concomitant acidosis, hypernatraemia and hyperosmolar syndrome. Herein, we report a rare presentation of CPM, which was purely secondary to hyperosmolar hyperglycaemia. The patient presented with ataxia and pseudobulbar affect, which evolved subacutely over a duration of two weeks. It is important to note that, in addition to acute changes in osmolality, a subacute shift secondary to hyperglycaemia may also lead to CPM. PMID:25917480

Acid-Base and the Skeleton

NASA Astrophysics Data System (ADS)

Bushinsky, David A.

2008-09-01

Chronic metabolic acidosis increases urine calcium (Ca) excretion in the absence of a concomitant increase in intestinal Ca absorption resulting in a net loss of total body. The source of this additional urine Ca is almost certainly the skeleton, the primary reservoir of body Ca. In vitro metabolic acidosis, modeled as a primary reduction in medium bicarbonate concentration, acutely (<24 h) stimulates Ca efflux primarily through physicochemical mineral dissolution while at later time periods (>24 h) cell-mediated mechanisms predominate. In cultured neonatal mouse calvariae, acidosis-induced, cell-mediated Ca efflux is mediated by effects on both osteoblasts and osteoclasts. Metabolic acidosis inhibits extracellular matrix production by osteoblasts, as determined by measurement of collagen levels and levels for the non-collagenous matrix proteins osteopontin and matrix gla protein. Metabolic acidosis upregulates osteoblastic expression of RANKL (Receptor Activator of NFκB Ligand), an important osteoclastogenic and osteoclast-activating factor. Acidosis also increases osteoclastic activity as measured by release of β-glucuronidase, an enzyme whose secretion correlates with osteoclast-mediated bone resorption.

Repeated ruminal acidosis challenges in lactating dairy cows at high and low risk for developing acidosis: feeding, ruminating, and lying behavior.

PubMed

DeVries, T J; Beauchemin, K A; Dohme, F; Schwartzkopf-Genswein, K S

2009-10-01

An experiment was conducted to determine whether the susceptibility to ruminal acidosis, as defined through differences in days in milk (DIM), milk production level, and ration composition, influences cow feeding, ruminating, and lying behavior and whether these behaviors change during an acute bout of ruminal acidosis. Eight ruminally cannulated cows were assigned to 1 of 2 acidosis risk levels: low risk (LR, mid-lactation cows fed a 60:40 forage:concentrate ratio diet) or high risk (HR, early lactation cows fed a 45:55 forage:concentrate diet). As a result, diets were intentionally confounded with DIM and milk production to represent 2 different acidosis risk scenarios. Cows were exposed to an acidosis challenge in each of three 14-d periods. Each period consisted of 3 baseline days, a feed restriction day (restricting total mixed ration to 50% of ad libitum intake), an acidosis challenge day (1 h meal of 4 kg of ground barley/wheat before allocating the total mixed ration), and a recovery phase. Feeding, rumination, and standing/lying behavior were recorded for 2 baseline days, on the challenge day, and 1 and 4 d after the challenge day for each cow. Across the study, there were no differences in measures of standing, lying, or feeding behavior between the 2 groups of cows. The HR cows did, on average, spend less time ruminating (491 vs. 555 min/d) than the LR cows, resulting in a lesser percentage of observed cows ruminating across the day (44.6 vs. 48.1%). The acidosis challenge resulted in changes in behavior in all cows. Compared with the baseline, feeding time increased on the first day after the challenge (395 vs. 310 min/d), whereas lying time decreased (565 vs. 634 min/d). Rumination time decreased the first day following the challenge (436 min/d) relative to the baseline (533 min/d), but increased the following day (572 min/d). Fewer cows were observed to be ruminating at a given time on the first day following the challenge as compared with the baseline period. Despite this, on a herd level, numerous observations of the proportion of cows ruminating at any one time would need to be taken to accurately detect an acute bout of acidosis using changes in rumination behavior. Overall, these results suggest that risk of acidosis may have little overall effect on general behavior, with the exception of rumination. Furthermore, an acute bout of acidosis alters behavioral patterns of lactating dairy cows, particularly rumination behavior, and identification of these changes in behavior through repeated measurements may assist in the detection of an acidosis event within a herd.

Physiological changes in rumen fermentation during acidosis induction and its control using a multivalent polyclonal antibody preparation in heifers.

PubMed

Blanch, M; Calsamiglia, S; DiLorenzo, N; DiCostanzo, A; Muetzel, S; Wallace, R J

2009-05-01

Physiological changes in rumen fermentation during acidosis induction and its control using a multivalent polyclonal antibody preparation (PAP) were studied in a completely randomized experiment using 12 crossbred heifers (452 +/- 20 kg of BW). Treatments were control (CTR) or PAP. The acidosis induction protocol consisted of 3 periods: 3 mo of 100% fescue hay fed for ad libitum intake, 10 d (from d 1 to 10 of the experiment) of adaptation to the treatment (100% forage feeding + 10 mL/d of PAP top-dressed to the treatment group), and 5 d (from d 11 to 15 of the experiment) of transition, which consisted of increasing the concentrate (16.5% CP) 2.5 kg/d up to 12.5 kg/d while maintaining ad libitum intake of fescue and providing 10 mL/d of PAP to the treated heifers. Concentrate feeding of 12.5 kg/d was maintained until heifers developed acidosis (from d 16 to 22 of the experiment). When an animal was considered acidotic, it was changed to a 50:50 forage:concentrate diet, monitored for 4 d, and removed from the experiment. Samples of ruminal fluid were collected before and 6 h after feeding to determine pH, VFA, lactate, protozoa counts, and DNA extraction for quantitative real-time PCR and denaturing gradient gel electrophoresis analyses. Only samples collected during adaptation to the treatment, at 3 and 1 d before acidosis, on the acidosis day, and at 1 and 4 d after acidosis were analyzed. Differences were declared at P < 0.05. Heifers (83% for CTR, and 50% for PAP) entered into acidosis 5.25 +/- 0.17 d after the beginning of the transition. The fermentation profile of animals with acidosis was similar between treatments. From 3 d before acidosis to acidosis day, decreases in pH and in acetate-to-propionate ratio and increases in total VFA, butyrate, and entodiniomorph counts were observed. However, the greatest concentrations of Streptococcus bovis and Megasphaera elsdenii (79 +/- 54 and 104 +/- 73 ng of DNA/mL of ruminal fluid, respectively) and a decrease in DMI (10.6 vs. 6.46 kg, respectively) were recorded 1 d after acidosis. Compared with CTR heifers, heifers fed PAP had greater pH before feeding on d 6 (6.70 vs. 6.11), 8 (6.54 vs. 5.95), and 9 (7.26 vs. 6.59) after the beginning of the feeding challenge. Heifers fed PAP tended to have greater total VFA concentrations than CTR (124 and 114 +/- 4.0 mM, respectively). These results indicate that PAP may be effective in controlling acidosis of heifers during a rapid transition to a high-concentrate diet.

Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets.

PubMed

Gordon, J B; Rehorst-Paea, L A; Hoffman, G M; Nelin, L D

1999-12-01

Acute alkalosis-induced pulmonary vasodilation and acidosis-induced pulmonary vasoconstriction have been well described, but responses were generally measured within 5-30 min of changing pH. In contrast, several in vitro studies have found that relatively brief periods of sustained alkalosis can enhance, and sustained acidosis can decrease, vascular reactivity. In this study of intact newborn piglets, effects of acute (20 min) and sustained (60-80 min) alkalosis or acidosis on baseline (35% O2) and hypoxic (12% O2) pulmonary vascular resistance (PVR) were compared with control piglets exposed only to eucapnia. Acute alkalosis decreased hypoxic PVR, but sustained alkalosis failed to attenuate either baseline PVR or the subsequent hypoxic response. Acute acidosis did not significantly increase hypoxic PVR, but sustained acidosis markedly increased both baseline PVR and the subsequent hypoxic response. Baseline PVR was similar in all piglets after resumption of eucapnic ventilation, but the final hypoxic response was greater in piglets previously exposed to alkalosis than in controls. Thus, hypoxic pulmonary vasoconstriction was not attenuated during sustained alkalosis, but was accentuated during sustained acidosis and after the resumption of eucapnia in alkalosis-treated piglets. Although extrapolation of data from normal piglets to infants and children with pulmonary hypertension must be done with caution, this study suggests that sustained alkalosis may be of limited efficacy in treating acute hypoxia-induced pulmonary hypertension and the risks of pulmonary hypertension must be considered when using ventilator strategies resulting in permissive hypercapnic acidosis.

Evaluation of in vitro models for predicting acidosis risk of barley grain in finishing beef cattle.

PubMed

Anele, U Y; Swift, M-L; McAllister, T A; Galyean, M L; Yang, W Z

2015-10-01

Our objective was to develop a model to predict the acidosis potential of barley based on the in vitro batch culture incubation of 50 samples varying in bulk density, starch content, processing method, growing location, and agronomic practices. The model was an adaptation of the acidosis index (calculated from a combination of in situ and in vitro analyses and from several components of grain chemical composition) developed in Australia for use in the feed industry to estimate the potential for grains to increase the risk of ruminal acidosis. Of the independent variables considered, DM disappearance at 6 h of incubation (DMD6) using reduced-strength (20%) buffer in the batch culture accounted for 90.5% of the variation in the acidosis index with a root mean square error (RMSE) of 4.46%. To evaluate our model using independent datasets (derived from previous batch culture studies using full-strength [100%] buffer), we performed another batch culture study using full-strength buffer. The full-strength buffer model using in vitro DMD6 (DMD6-FS) accounted for 66.5% of the variation in the acidosis index with an RMSE of 8.30%. When the new full-strength buffer model was applied to 3 independent datasets to predict acidosis, it accounted for 20.1, 28.5, and 30.2% of the variation in the calculated acidosis index. Significant ( < 0.001) mean bias was evident in 2 of the datasets, for which the DMD6 model underpredicted the acidosis index by 46.9 and 5.73%. Ranking of samples from the most diverse independent dataset using the DMD6-FS model and the Black (2008) model (calculated using in situ starch degradation) indicated the relationship between the rankings using Spearman's rank correlation was negative (ρ = -0.30; = 0.059). When the reduced-strength buffer model was used, however, there were similarities in the acidosis index ranking of barley samples by the models as shown by the result of a correlation analysis between calculated (using the Australian model) and predicted (using the reduced-strength buffer DMD6 model) acidosis index (ρ = 0.67; < 0.001). Results suggest that our model, which is based on a reduced-strength buffer in vitro DMD6, has the potential to predict acidosis risk and can rank barley samples based on their acidotic risk. Nonetheless, the model would benefit from further refinement by expanding the database.

Acidosis slows electrical conduction through the atrio-ventricular node

PubMed Central

Nisbet, Ashley M.; Burton, Francis L.; Walker, Nicola L.; Craig, Margaret A.; Cheng, Hongwei; Hancox, Jules C.; Orchard, Clive H.; Smith, Godfrey L.

2014-01-01

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis. PMID:25009505

Acidosis slows electrical conduction through the atrio-ventricular node.

PubMed

Nisbet, Ashley M; Burton, Francis L; Walker, Nicola L; Craig, Margaret A; Cheng, Hongwei; Hancox, Jules C; Orchard, Clive H; Smith, Godfrey L

2014-01-01

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis.

Why are dairy cows not able to cope with the subacute ruminal acidosis?

PubMed

Brzozowska, A M; Sloniewski, K; Oprzadek, J; Sobiech, P; Kowalski, Z M

2013-01-01

One of the largest challenges for the dairy industry is to provide cows with a diet which is highly energetic but does not negatively affect their rumens' functions. In highly productive dairy cows, feeding diets rich in readily fermentable carbohydrates provides energy precursors needed for maximum milk production, but simultaneously decreases ruminal pH, leading to a widespread prevalence of subacute ruminal acidosis. Maximizing milk production without triggering rumen acidosis still challenges dairy farmers, who try to prevent prolonged bouts of low ruminal pH mainly by proper nutrition and management practices. The animals try to avoid overeating fermentable feeds, as it causes negative consequences by disturbing digestive processes. The results of several experiments show that ruminants, including sheep and beef cattle, are able to modify some aspects of feeding behaviour in order to adjust nutrient intake to their needs and simultaneously prevent physiological disturbances. Particularly, such changes (e.g., increased preference for fibrous feeds, reduced intake of concentrates) were observed in animals, which were trying to prevent the excessive drop of rumen fluid pH. Thanks to a specific mechanism called "the postingestive feedback", animals should be able to work out such a balance in intake, so they do not suffer either from hunger or from negative effects of over-ingesting the fermentable carbohydrates. This way, an acidosis should not be a frequent problem in ruminants. However, prolonged periods of excessively decreased rumen pH are still a concern in dairy cows. It raises a question, why the regulation of feed intake by postingestive feedback does not help to maintain stable rumen environment in dairy cows?

Complicated pregnancies in inherited distal renal tubular acidosis: importance of acid-base balance.

PubMed

Seeger, Harald; Salfeld, Peter; Eisel, Rüdiger; Wagner, Carsten A; Mohebbi, Nilufar

2017-06-01

Inherited distal renal tubular acidosis (dRTA) is caused by impaired urinary acid excretion resulting in hyperchloremic metabolic acidosis. Although the glomerular filtration rate (GFR) is usually preserved, and hypertension and overt proteinuria are absent, it has to be considered that patients with dRTA also suffer from chronic kidney disease (CKD) with an increased risk for adverse pregnancy-related outcomes. Typical complications of dRTA include severe hypokalemia leading to cardiac arrhythmias and paralysis, nephrolithiasis and nephrocalcinosis. Several physiologic changes occur in normal pregnancy including alterations in acid-base and electrolyte homeostasis as well as in GFR. However, data on pregnancy in women with inherited dRTA are scarce. We report the course of pregnancy in three women with hereditary dRTA. Complications observed were severe metabolic acidosis, profound hypokalemia aggravated by hyperemesis gravidarum, recurrent urinary tract infection (UTI) and ureteric obstruction leading to renal failure. However, the outcome of all five pregnancies (1 pregnancy each for mothers n. 1 and 2; 3 pregnancies for mother n. 3) was excellent due to timely interventions. Our findings highlight the importance of close nephrologic monitoring of women with inherited dRTA during pregnancy. In addition to routine assessment of creatinine and proteinuria, caregivers should especially focus on acid-base status, plasma potassium and urinary tract infections. Patients should be screened for renal obstruction in the case of typical symptoms, UTI or renal failure. Furthermore, genetic identification of the underlying mutation may (a) support early nephrologic referral during pregnancy and a better management of the affected woman, and (b) help to avoid delayed diagnosis and reduce complications in affected newborns.

A mass cyanide poisoning from pickling bamboo shoots.

PubMed

Sang-A-Gad, Pensiriwan; Guharat, Suriya; Wananukul, Winai

2011-11-01

Bamboo shoots contain cyanogenic glycosides named taxiphyllin. Cyanide poisoning from cyanogenic glycosides commonly occurs following ingestion. However, toxicity caused by inhalation of hydrogen cyanide gas (HCN) produced from pickled shoots has never been reported. To describe cyanide poisoning in eight victims who were exposed to HCN produced in a well containing pickling bamboo shoots. Due to a series of botched rescue attempts, a total of eight patients entered into a 27 m(3) well containing pickled bamboo shoots and immediately lost consciousness. After rescue, two patients developed cardiac arrest, metabolic acidosis and died. Four other patients suffered metabolic acidosis, but recovered after supportive care. The remaining two regained consciousness and recovered soon after the event. Ambient air study and cyanide content of bamboo shoots helped confirm the diagnosis. All patients had high anion gap metabolic acidosis with normal oxygenation. Blood cyanide levels ranged from 2.66 to 3.30 mcg/ml (taken after about 18 h of incident). Ambient air study (21 h after incident) revealed oxygen 20.9%, and sulfur dioxide 19.4 ppm. The instrument was unfortunately not equipped to detect HCN. A simulation study revealed HCN and sulfur dioxide in the ambient air at 10 ppm and 7.5 ppm, respectively. Cyanide content in the bamboo shoots ranged from 39 to 434 mg/kg in the wet shoots. This series of patients developed sudden onset of alteration of consciousness and metabolic acidosis upon exposure, and cyanide was confirmed in all victims. The simulation study confirmed the presence of HCN in the ambient air of the well containing bamboo shoots. We have reported mass acute cyanide poisoning with two fatalities. The source of HCN was unusual as it was produced from pickling bamboo shoot.

Effects of acute hypoxia/acidosis on intracellular pH in differentiating neural progenitor cells.

PubMed

Nordström, Tommy; Jansson, Linda C; Louhivuori, Lauri M; Akerman, Karl E O

2012-06-21

The response of differentiating mouse neural progenitor cells, migrating out from neurospheres, to conditions simulating ischemia (hypoxia and extracellular or intracellular acidosis) was studied. We show here, by using BCECF and single cell imaging to monitor intracellular pH (pH(i)), that two main populations can be distinguished by exposing migrating neural progenitor cells to low extracellular pH or by performing an acidifying ammonium prepulse. The cells dominating at the periphery of the neurosphere culture, which were positive for neuron specific markers MAP-2, calbindin and NeuN had lower initial resting pH(i) and could also easily be further acidified by lowering the extracellular pH. Moreover, in this population, a more profound acidification was seen when the cells were acidified using the ammonium prepulse technique. However, when the cell population was exposed to depolarizing potassium concentrations no alterations in pH(i) took place in this population. In contrast, depolarization caused an increase in pH(i) (by 0.5 pH units) in the cell population closer to the neurosphere body, which region was positive for the radial cell marker (GLAST). This cell population, having higher resting pH(i) (pH 6.9-7.1) also responded to acute hypoxia. During hypoxic treatment the resting pH(i) decreased by 0.1 pH units and recovered rapidly after reoxygenation. Our results show that migrating neural progenitor cells are highly sensitive to extracellular acidosis and that irreversible damage becomes evident at pH 6.2. Moreover, our results show that a response to acidosis clearly distinguishes two individual cell populations probably representing neuronal and radial cells. Copyright © 2012 Elsevier B.V. All rights reserved.

Ruminal Acidosis in Feedlot: From Aetiology to Prevention

PubMed Central

Hernández, Joaquín; Benedito, José Luis; Abuelo, Angel; Castillo, Cristina

2014-01-01

Acute ruminal acidosis is a metabolic status defined by decreased blood pH and bicarbonate, caused by overproduction of ruminal D-lactate. It will appear when animals ingest excessive amount of nonstructural carbohydrates with low neutral detergent fiber. Animals will show ruminal hypotony/atony with hydrorumen and a typical parakeratosis-rumenitis liver abscess complex, associated with a plethora of systemic manifestations such as diarrhea and dehydration, liver abscesses, infections of the lung, the heart, and/or the kidney, and laminitis, as well as neurologic symptoms due to both cerebrocortical necrosis and the direct effect of D-lactate on neurons. In feedlots, warning signs include decrease in chewing activity, weight, and dry matter intake and increase in laminitis and diarrhea prevalence. The prognosis is quite variable. Treatment will be based on the control of systemic acidosis and dehydration. Prevention is the most important tool and will require normalization of ruminal pH and microbiota. Appropriate feeding strategies are essential and involve changing the dietary composition to increase neutral detergent fiber content and greater particle size and length. Appropriate grain processing can control the fermentation rate while additives such as prebiotics or probiotics can help to stabilize the ruminal environment. Immunization against producers of D-lactate is being explored. PMID:25489604

A Rare Cause of Metabolic Acidosis: Fatal Transdermal Methanol Intoxication in an Infant.

PubMed

Sahbudak Bal, Zumrut; Can, Fulya Kamit; Anil, Ayse Berna; Bal, Alkan; Anil, Murat; Gokalp, Gamze; Yavascan, Onder; Aksu, Nejat

2016-08-01

Oral methanol intoxication is common, but dermal intoxication is rare. We report a previously healthy 19-month-old female infant admitted to the emergency department (ED) with vomiting and tonic-clonic seizure. On physical examination, she was comatose and presented signs of decompensated shock with Kussmaul breathing. Her left thigh was edematous, with purple coloration. Methanol intoxication was suspected due to high anion gap metabolic acidosis (pH, 6.89; HCO3, <3 meq/L) and exposure to spirit-soaked bandages (%96 methanol) for 24 hours and 3 days. The patient's serum methanol level was 20.4 mg/dL. She was treated with fomepizole and continuous venovenous hemodialysis (CVVHD) in the pediatric intensive care unit, and methanol levels decreased to 0 mg/dL after 12 hours. During follow-up, massive edema and subarachnoid hemorrhage in the occipital lobe were detected by computed tomography of the brain. The patient died after 7 days.Although methanol intoxication occurs predominantly in adults, it must be considered in children with high-anion gap metabolic acidosis. This case report demonstrates that fatal transdermal methanol intoxication can occur in children, and it is the second report in the English literature of transdermal methanol intoxication in an infant.

Lactic Acidosis with Chloramphenicol Treatment in a Child with Cystic Fibrosis.

PubMed

Goyer, Isabelle; Iseppon, Massimiliano; Thibault, Céline; Abaji, Rachid; Krajinovic, Maja; Autmizguine, Julie

2017-01-30

Children with cystic fibrosis are commonly colonized with multi-resistant bacteria. In such patients, infectious exacerbation may require salvage therapy with uncommonly used antimicrobials, including chloramphenicol. Chloramphenicol is rarely used nowadays because of the associated severe adverse events. We describe the case of a 15-year-old female with terminal cystic fibrosis who required intravenous (IV) chloramphenicol treatment for a Burkholderia cepacia (B. cepacia) exacerbation. The child subsequently developed lactic acidosis and secondary respiratory compensation adding to her baseline respiratory distress. Based on the Naranjo scale, the probability of chloramphenicol being the cause of the hyperlactatemia and associated respiratory distress was rated as probable, as the adverse effects resolved upon discontinuation of the drug. Subsequent genotyping for mitochondrial polymorphism (G3010A) confirmed a possible susceptibility to lactic acidosis from mitochondrial RNA-inhibiting agents such as chloramphenicol. Hyperlactatemia is a rare but life threatening adverse effect that has been previously reported with chloramphenicol exposure, but is not generally thought of. Clinicians should be aware of this potentially life threatening, but reversible adverse event. Lactate should be monitored under chloramphenicol and it should be discontinued as soon as this complication is suspected, especially in patients with low respiratory reserve. © 2017 Journal of Population Therapeutics and Clinical Pharmacology. All rights reserved.

Effects of lactic acid on astrocytes in primary culture.

PubMed

Norenberg, M D; Mozes, L W; Gregorios, J B; Norenberg, L O

1987-03-01

Excessive tissue lactic acidosis is considered to be detrimental to the central nervous system (CNS) and may adversely affect recovery from anoxia, ischemia, trauma and epilepsy. Since astrocytes are believed to play a role in pH regulation in the CNS, we studied the effect of this acid on primary astrocyte cultures. Cells exposed to lactic acid showed chromatin clumping, an increase of lipid and dense bodies, a loss of polyribosomal clusters, slightly increased cytoplasmic lucency, swollen mitochondria and tangled intermediate filaments. These alterations progressed with lower pH and longer exposure. Irreversible changes occurred one to two hours after exposure at pH 6; after 30 to 60 minutes (min) at pH 5.5 and after ten to 30 min at pH 5. Comparable results were obtained with the use of other weak acids indicating that the observed changes were due to increased hydrogen ion concentration rather than secondary to lactate per se. Additionally, various concentrations of lactic acid adjusted to identical pH produced similar morphologic alterations. Thus, while lactic acid caused marked and at times irreversible alterations in astrocytes, severe and prolonged acidosis was required to produce such injurious effects. This relative resistance of astrocytes to acidosis is in keeping with their potential role in pH regulation in brain.

Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories.

PubMed

Brewer, Gregory J

2010-03-01

Harman's free radical theory of aging posits that oxidized macromolecules accumulate with age to decrease function and shorten life-span. However, nutritional and genetic interventions to boost anti-oxidants have generally failed to increase life-span. Furthermore, the free radical theory fails to explain why exercise causes higher levels of oxyradical damage, but generally promotes healthy aging. The separate anti-aging paradigms of genetic or caloric reductions in the insulin signaling pathway is thought to slow the rate of living to reduce metabolism, but recent evidence from Westbrook and Bartke suggests metabolism actually increases in long-lived mice. To unify these disparate theories and data, here, we propose the epigenetic oxidative redox shift (EORS) theory of aging. According to EORS, sedentary behavior associated with age triggers an oxidized redox shift and impaired mitochondrial function. In order to maintain resting energy levels, aerobic glycolysis is upregulated by redox-sensitive transcription factors. As emphasized by DeGrey, the need to supply NAD(+) for glucose oxidation and maintain redox balance with impaired mitochondrial NADH oxidoreductase requires the upregulation of other oxidoreductases. In contrast to the 2% inefficiency of mitochondrial reduction of oxygen to the oxyradical, these other oxidoreductases enable glycolytic energy production with a deleterious 100% efficiency in generating oxyradicals. To avoid this catastrophic cycle, lactate dehydrogenase is upregulated at the expense of lactic acid acidosis. This metabolic shift is epigenetically enforced, as is insulin resistance to reduce mitochondrial turnover. The low mitochondrial capacity for efficient production of energy reinforces a downward spiral of more sedentary behavior leading to accelerated aging, increased organ failure with stress, impaired immune and vascular functions and brain aging. Several steps in the pathway are amenable to reversal for exit from the vicious cycle of EORS. Examples from our work in the aging rodent brain as well as other aging models are provided. Copyright 2010 Elsevier Inc. All rights reserved.

Coagulation Changes to Systemic Acidosis and Bicarbonate Correction in Swine

DTIC Science & Technology

2011-11-01

carbonate. Total experiment time and time between Base - line, Acidosis, and Acidosis-Corrected varied from pig to pig. y axis describes the pH of the swine...Infusion of HCl reduced arterial pH from 7.4 to 7.1 and also reduced HCO3 , base excess (BE), and PaCO2 (Acidosis, Table 1). In this group, bicarbonate...a decrease in respiration successfully lowered arterial pH to 7.1 ( Acido - sis, Table 2) and significantly elevated PaCO2 and HCO3 and lowered PaO2

Hemolytic anemia and metabolic acidosis: think about glutathione synthetase deficiency.

PubMed

Ben Ameur, Salma; Aloulou, Hajer; Nasrallah, Fehmi; Kamoun, Thouraya; Kaabachi, Naziha; Hachicha, Mongia

2015-02-01

Glutathione synthetase deficiency (GSSD) is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with hemolytic anemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low glutathione synthetase activity in erythrocytes or cultured skin fibroblasts. The prognosis seems to depend on early diagnosis and treatment. We report a 4 months old Tunisian male infant who presented with severe metabolic acidosis with high anion gap and hemolytic anemia. High level of 5-oxoproline was detected in her urine and diagnosis of GSSD was made. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. He died of severe metabolic acidosis and sepsis at the age of 15 months.

Comparison of the alkalizing effects of bicarbonate precursors in calves with experimentally induced metabolic acidosis.

PubMed

Nakagawa, Mitsuhide; Suzuki, Kazuyuki; Takahashi, Fumito; Kamikatano, Kazuhiro; Koiwa, Masateru; Taguchi, Kiyoshi

2009-06-01

The aims of this study were to confirm whether commercial acetated Ringer's solution, which contains 28 mM of sodium acetate, is superior to commercial lactated Ringer's solution in alkalizing effects in calves with experimentally induced metabolic acidosis. Twenty calves with experimentally induced mild acidosis were intravenously administered isotonic saline, DL-lactated, L-lactated or acetated Ringer's solution at a dose of 80 ml/kg body weight (BW). The acetated Ringer's solution induced a significantly greater increase in venous HCO(3)(-) and base excess concentrations than the other fluids during the early phases of extracellular fluid replacement in mild metabolic acidosis. Therefore, the alkalizing effect of commercial acetated Ringer's solution is superior to commercial DL- and L-lactated Ringer's solution in treatment of mild metabolic acidosis in calves.

Theory of gastric CO2 ventilation and its control during respiratory acidosis: implications for central chemosensitivity, pH regulation, and diseases causing chronic CO2 retention.

PubMed

Dean, Jay B

2011-02-15

The theory of gastric CO(2) ventilation describes a previously unrecognized reflex mechanism controlled by neurons in the caudal solitary complex (cSC) for non-alveolar elimination of systemic CO(2) during respiratory acidosis. Neurons in the cSC, which is a site of CO(2) chemosensitivity for cardiorespiratory control, also control various gastroesophageal reflexes that remove CO(2) from blood. CO(2) is consumed in the production of gastric acid and bicarbonate in the gastric epithelium and then reconstituted as CO(2) in the stomach lumen from the reaction between H(+) and HCO(3)(-). Respiratory acidosis and gastric CO(2) distension induce cSC/vagovagal mediated transient relaxations of the lower esophageal sphincter to vent gastric CO(2) upwards by bulk flow along an abdominal-to-esophageal (=intrapleural) pressure gradient the magnitude of which increases during abdominal (gastric) compression caused by increased contractions of respiratory muscles. Esophageal distension induces cSC/nucleus ambiguus/vagovagal reflex relaxation of the upper esophageal sphincter and CO(2) is vented into the pharynx and mixed with pulmonary gas during expiration or, alternatively, during eructation. It is proposed that gastric CO(2) ventilation provides explanations for (1) the postprandial increase in expired CO(2) and (2) the negative P(blood - expired)CO₂difference that occurs with increased inspired CO(2). Furthermore, it is postulated that gastric CO(2) ventilation and alveolar CO(2) ventilation are coordinated under dual control by CO(2) chemosensitive neurons in the cSC. This new theory, therefore, presupposes a level of neural control and coordination between two previously presumed dissimilar organ systems and supports the notion that different sites of CO(2) chemosensitivity address different aspects of whole body pH regulation. Consequently, not all sites of central chemosensitivity are equal regarding the mechanism(s) activated for CO(2) elimination. A distributed CO(2) chemosensitive network-at least nine different areas in the CNS, including the cSC, have been reported to date-may reflect the complexity and dynamic nature of the fundamental neural circuitry required to achieve CO(2)/pH regulation across multiple organ systems under various states of arousal, oxygenation, pH status, and redox state. Moreover, coordination of respiratory and digestive control networks through the cSC could also account for the frequent co-expression of pulmonary diseases that cause chronic respiratory acidosis (and overstimulation of cSC neurons) with peptic ulcer disease or gastroesophageal reflux disease. Copyright © 2010 Elsevier B.V. All rights reserved.

Role of hemolysis in red cell adenosine triphosphate release in simulated exercise conditions in vitro.

PubMed

Mairbäurl, Heimo; Ruppe, Florian A; Bärtsch, Peter

2013-10-01

Specific adenosine triphosphate (ATP) release from red blood cells has been discussed as a possible mediator controlling microcirculation in states of decreased tissue oxygen. Because intravascular hemolysis might also contribute to plasma ATP, we tested in vitro which portion of ATP release is due to hemolysis in typical exercise-induced strains to the red blood cells (shear stress, deoxygenation, and lactic acidosis). Human erythrocytes were suspended in dextran-containing media (hematocrit 10%) and were exposed to shear stress in a rotating Couette viscometer at 37°C. Desaturation (oxygen saturation of hemoglobin ∼20%) was achieved by tonometry with N2 before shear stress exposure. Cells not exposed to shear stress were used as controls. Na lactate (15 mM), lactic acid (15 mM, pH 7.0), and HCl (pH 7.0) were added to simulate exercise-induced lactic acidosis. After incubation, extracellular hemoglobin was measured to quantify hemolysis. ATP was measured with the luciferase assay. Shear stress increased extracellular ATP in a stress-related and time-dependent manner. Hypoxia induced a ∼10-fold increase in extracellular ATP in nonsheared cells and shear stress-exposed cells. Lactic acid had no significant effect on ATP release and hemolysis. In normoxic cells, approximately 20%-50% of extracellular ATP was due to hemolysis. This proportion decreased to less than 10% in hypoxic cells. Our results indicate that when exposing red blood cells to typical strains they encounter when passing through capillaries of exercising skeletal muscle, ATP release from red blood cells is caused mainly by deoxygenation and shear stress, whereas lactic acidosis had only a minor effect. Hemolysis effects were decreased when hemoglobin was deoxygenated. Together, by specific release and hemolysis, extracellular ATP reaches values that have been shown to cause local vasodilatation.

The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats.

PubMed

Imber, Ann N; Patrone, Luis G A; Li, Ke-Yong; Gargaglioni, Luciane H; Putnam, Robert W

2018-06-15

The cellular mechanisms by which LC neurons respond to hypercapnia are usually attributed to an "accelerator" whereby hypercapnic acidosis causes an inhibition of K + channels or activation of Na + and Ca +2 channels to depolarize CO 2 -sensitive neurons. Nevertheless, it is still unknown if this "accelerator" mechanism could be controlled by a brake phenomenon. Whole-cell patch clamping, fluorescence imaging microscopy and plethysmography were used to study the chemosensitive response of the LC neurons. Hypercapnic acidosis activates L-type Ca 2+ channels and large conductance Ca-activated K + (BK) channels, which function as a "brake" on the chemosensitive response of LC neurons. Our findings indicate that both Ca 2+ and BK currents develop over the first 2 weeks of postnatal life in rat LC slices and that this brake pathway may cause the developmental decrease in the chemosensitive firing rate response of LC neurons to hypercapnic acidosis. Inhibition of this brake by paxilline (BK channel inhibitor) returns the magnitude of the chemosensitive firing rate response from LC neurons in rats older than P10 to high values similar to those in LC neurons from younger rats. Inhibition of BK channels in LC neurons by bilateral injections of paxilline into the LC results in a significant increase in the hypercapnic ventilatory response of adult rats. Our findings indicate that a BK channel-based braking system helps to determine the chemosensitive respiratory drive of LC neurons and contributes to the hypercapnic ventilatory response. Perhaps, abnormalities of this braking system could result in hypercapnia-induced respiratory disorders and panic responses. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

D-lactic acid interferes with the effects of platelet activating factor on bovine neutrophils.

PubMed

Alarcón, P; Conejeros, I; Carretta, M D; Concha, C; Jara, E; Tadich, N; Hidalgo, M A; Burgos, R A

2011-11-15

D-lactic acidosis occurs in ruminants, such as cattle, with acute ruminal acidosis caused by ingestion of excessive amounts of highly fermentable carbohydrates. Affected animals show clinical signs similar to those of septic shock, as well as acute laminitis and liver abscesses. It has been proposed that the inflammatory response and susceptibility to infection could both be caused by the inhibition of phagocytic mechanisms. To determine the effects of d-lactic acid on bovine neutrophil functions, we pretreated cells with different concentrations of D-lactic acid and measured intracellular pH using 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM) and calcium flux using FLUO-3 AM-loaded neutrophils. Reactive oxygen species (ROS) production was measured using a luminol chemiluminescence assay, and MMP-9/gelatinase-B granule release was measured by zymography. CD11b and CD62L/l-selectin expression, changes in cell shape, superoxide anion production, phagocytosis of Escherichia coli-Texas red bioparticles, and apoptosis were all measured using flow cytometry. Our results demonstrated that D-lactic acid reduced ROS production, CD11b upregulation and MMP-9 release in bovine neutrophils treated with 100 nM platelet-activating factor (PAF). D-lactic acid induced MMP-9 release and, at higher concentrations, upregulated CD11b expression, decrease L-selectin expression, and induces late apoptosis. We concluded that D-lactic acid can interfere with neutrophil functions induced by PAF, leading to reduced innate immune responses during bacterial infections. Moreover, the increase of MMP-9 release and CD11b expression induced by 10mM D-lactic acid could promote an nonspecific neutrophil-dependent inflammatory reaction in cattle with acute ruminal acidosis. Copyright © 2011 Elsevier B.V. All rights reserved.

Experimentally induced hyperchloremic and DL-lactic acidosis in calves: an attempt to study the effects of oral rehydration on acid-base status.

PubMed

Schwedhelm, L; Kirchner, D; Klaus, B; Bachmann, L

2013-04-01

Many diarrheic calves suffer from metabolic acidosis, which is commonly treated by oral rehydration therapy. Oral rehydration solutions can be prepared in water, milk, or milk replacer. Therefore, the aim of the study was to verify dietary effects of water- or milk replacer-based oral rehydration solutions on parameters of acid-base balance in calves with experimentally induced hyperchloremic and dl-lactate acidosis. In 12 calves, hyperchloremic or dl-lactate acidosis was induced by HCl or dl-lactic acid infusions according to protocols outlined in previous literature. Immediately after induction, the calves were fed with milk replacer or water- or milk replacer-based oral rehydration solutions, or remained fasting, respectively. Blood samples were taken to monitor acid-base status over an experimental period of 4h. Using the protocols, all calves revealed a manifest hyperchloremic or dl-lactate acidosis. Because of high infusion volumes, plasma volume was expanded and effects of feeding regimens on blood parameters were rare. Unexpected clinical aberrations occurred after repeated induction of dl-lactate acidosis: all calves developed a thrombophlebitis of the jugular vein, whereas HCl infusion had no effect on endothelium. Induction of acidosis via infusion is not suitable to study dietary effects. A protocol to induce acidosis and dehydration simultaneously is required to duplicate the metabolic conditions of diarrheic calves. In further investigations, attention should be focused on effects of d-lactate or its metabolites on endothelial tissue. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Development of a diagnostic diagram for rapid field assessment of acidosis severity in diarrheic calves.

PubMed

Bellino, Claudio; Arnaudo, Fabrizio; Biolatti, Cristina; Borrelli, Antonio; Gianella, Paola; Maurella, Cristiana; Zabaldano, Giuseppe; Cagnasso, Aurelio; D'Angelo, Antonio

2012-02-01

To develop a diagnostic diagram for rapid field assessment of acidosis severity in diarrheic calves. Prospective cross-sectional study. 148 Piedmontese calves (38 calves in preliminary experiments; 83 diarrheic calves and 27 healthy control calves in the primary experiment). Physical examination was performed and a standard data collection form was completed for each calf. Blood samples were obtained and submitted for evaluation of acid-base balance, performance of a CBC, and measurement of electrolyte and total protein concentrations. Severe metabolic acidosis (extracellular base excess more negative than -10 mmol/L) was associated with abnormal mental status, delayed or absent suckle reflex, abnormal posture or gait, enophthalmos, and cold oral mucosal membranes. Clinical signs associated with severe metabolic acidosis were arranged into a grid to create a diagnostic diagram. Sensitivity and specificity of the diagnostic diagram for the prediction of severe metabolic acidosis were 88% and 79%, respectively. Use of the diagnostic diagram may aid differentiation between severe and nonsevere acidosis patterns as determined on the basis of clinical signs.

Acute kidney injury, plasma lactate concentrations and lactic acidosis in metformin users: A GoDarts study.

PubMed

Connelly, Paul J; Lonergan, Mike; Soto-Pedre, Enrique; Donnelly, Louise; Zhou, Kaixin; Pearson, Ewan R

2017-11-01

Metformin is renally excreted and has been associated with the development of lactic acidosis. Although current advice is to omit metformin during illnesses that may increase the risk of acute kidney injury (AKI), the evidence supporting this is lacking. We investigated the relationship between AKI, lactate concentrations and the risk of lactic acidosis in those exposed to metformin. We undertook a population-based case-control study of lactic acidosis in 1746 participants with Type 2 diabetes and 846 individuals without diabetes with clinically measured lactates with and without AKI between 1994 and 2014. AKI was stratified by severity according to "Kidney Disease: Improving Global Outcomes" guidelines. Mixed-effects logistic and linear regression were used to analyse lactic acidosis risk and lactate concentrations, respectively. Eighty-two cases of lactic acidosis were identified. In Type 2 diabetes, those treated with metformin had a greater incidence of lactic acidosis [45.7 per 100 000 patient years; 95% confidence interval (CI) 35.9-58.3] compared to those not exposed to this drug (11.8 per 100 000 patient years; 95% CI 4.9-28.5). Lactate concentrations were 0.34 mmol/L higher in the metformin-exposed cohort (P < .001). The risk of lactic acidosis was higher in metformin users [odds ratio (OR) 2.3; P = .002] and increased with AKI severity (stage 1: OR 3.0, P = .002; stage 2: OR 9.4, P < .001; stage 3: OR 16.1, P < .001). A clear association was found between metformin, lactate accumulation and the development of lactic acidosis. This relationship is strongest in those with AKI. These results provide robust evidence to support current recommendations to omit metformin in any illness that may precipitate AKI. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Acidosis Activation of the Proton-Sensing GPR4 Receptor Stimulates Vascular Endothelial Cell Inflammatory Responses Revealed by Transcriptome Analysis

PubMed Central

Dong, Lixue; Li, Zhigang; Leffler, Nancy R.; Asch, Adam S.; Chi, Jen-Tsan; Yang, Li V.

2013-01-01

Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular mechanisms by which cells sense and respond to the acidic microenvironment are not well understood. GPR4 is a proton-sensing receptor expressed in endothelial cells and other cell types. The receptor is fully activated by acidic extracellular pH but exhibits lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To delineate the function and signaling pathways of GPR4 activation by acidosis in endothelial cells, we compared the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC) with varying level of GPR4. The results demonstrated that acidosis activation of GPR4 in HUVEC substantially increased the expression of a number of inflammatory genes such as chemokines, cytokines, adhesion molecules, NF-κB pathway genes, and prostaglandin-endoperoxidase synthase 2 (PTGS2 or COX-2) and stress response genes such as ATF3 and DDIT3 (CHOP). Similar GPR4-mediated acidosis induction of the inflammatory genes was also noted in other types of endothelial cells including human lung microvascular endothelial cells and pulmonary artery endothelial cells. Further analyses indicated that the NF-κB pathway was important for the acidosis/GPR4-induced inflammatory gene expression. Moreover, acidosis activation of GPR4 increased the adhesion of HUVEC to U937 monocytic cells under a flow condition. Importantly, treatment with a recently identified GPR4 antagonist significantly reduced the acidosis/GPR4-mediated endothelial cell inflammatory response. Taken together, these results show that activation of GPR4 by acidosis stimulates the expression of a wide range of inflammatory genes in endothelial cells. Such inflammatory response can be suppressed by GPR4 small molecule inhibitors and hold potential therapeutic value. PMID:23613998

[Diagnosis of neonatal metabolic acidosis by eucapnic pH determination].

PubMed

Racinet, C; Richalet, G; Corne, C; Faure, P; Peresse, J-F; Leverve, X

2013-09-01

The identification of a metabolic acidosis is a key criterion for establishing a causal relationship between fetal perpartum asphyxia and neonatal encephalopathy and/or cerebral palsy. The diagnostic criteria currently used (pH and base deficit or lactatemia) are imprecise and non-specific. The study aimed to determine among a low-risk cohort of infants born at term (n = 867), the best diagnostic tool of metabolic acidosis in the cordonal from the following parameters: pH, blood gases and lactate values at birth. The data were obtained from arterial blood of the umbilical cord by a blood gas analyser. The parameter best predicting metabolic analysis was estimated from the partial correlations established between the most relevant parameters. The results showed a slight change in all parameters compared to adult values: acidemia (pH: 7.28 ± 0.01), hypercapnia (56.5 ± 1.59 mmHg) and hyperlactatemia (3.4 ± 0.05 mmol/L). From partial correlation analysis, pCO(2) emerged to be the main contributor of acidemia, while lactatemia was shown to be non-specific for metabolic acidosis. Seven cases (0.81 %) showed a pH less than 7.00 with marked hypercapnia. The correction of this respiratory component by EISENBERG's method led to the eucapnic pH, classifying six out of seven cases as exclusive respiratory acidosis. It has been demonstrated that the criteria from ACOG-AAP for defining a metabolic acidosis are incomplete, imprecise and generating errors in excess. The same is true for lactatemia, whose physiological significance has been completely revised, challenging the misconception of lactic acidosis as a specific marker of hypoxia. It appeared that eucapnic pH was the best way for obtaining a reliable diagnosis of metabolic acidosis. We proposed to adopt a simple decision scheme for determining whether a metabolic acidosis has occurred in case of acidemia less than 7.00. Copyright © 2013. Published by Elsevier SAS.

High dietary sodium chloride causes further protein loss during head-down tilt bed rest (HDBR)

NASA Astrophysics Data System (ADS)

Buehlmeier, Judith; Frings-Meuthen, Petra; Baecker, Natalie; Stehle, Peter; Heer, Martina

Human spaceflight is associated with a loss of body protein most likely caused by muscle degradation. Additionally astronauts tend towards a high dietary intake of sodium chloride (NaCl), which has recently been shown to induce low grade metabolic acidosis (Frings-Meuthen et al. JBMR, Epub 2007). In several patterns, e.g. chronical renal failure, metabolic acidosis is associated with protein catabolism. We therefore hypothesized that high dietary intake of NaCl enforces protein losses in HDBR, a model for physiological changes in microgravity (µG). Eight healthy male subjects (mean age 26.25 ± 3.5; mean body weight: 78.5 ± 4.1 kg) participated in a 14-day bed rest study in the metabolic ward of the DLR - Institute of Aerospace Medicine, Cologne, Germany. The study was carried out in a cross over design, consisting of two phases, each lasting 22 days (5 days adaptation, 14 days 6° HDBR and 3 days recovery). Both study phases were identical with respect to environmental conditions and study protocol. Subjects received an individually tailored, weight-maintaining diet containing 1.3 g protein/kg/day. The diet was identical in both study phases with the exception of NaClintake: Every subject received a low NaCl diet (0.7 mmol/kg/day) in one phase and a high NaCl diet (7.7 mmol/kg/day) in another one. Blood gas for analysis of acid-base balance was implemented at days 4 and 5 of adaptation, days 2, 5, 7, 10, 12, 14 of HDBR and days 2, 3 of recovery. Continuous urine collection started on the first day in the metabolic ward to analyze nitrogen excretion. Nitrogen balance was calculated from the difference between protein intake and urinary nitrogen excretion, determined by use of chemiluminescence (Grimble et al. JPEN, 1988). Plasma pH did not change significantly (p=0.285), but plasma bicarbonate and base excess decreased (p=0.0175; p=0.0093) with high NaCl intake in HDBR compared to the low NaCl diet. Nitrogen balance in HDBR was negative, as expected in immobilization with low NaCl diet ( 0.34 ± 1.2 g/d). However, high NaCl intake in HDBR exacerbated the negative nitrogen balance to 1.34 ± 1.0 g/d (p¡0.001) compared to low NaCl. We conclude that high dietary NaCl intake induces low grade metabolic acidosis during HDBR. Low grade metabolic acidosis may be a reason for an increased protein turnover reflected by an exaggerated negative nitrogen balance in HDBR. Accordingly, a high dietary NaCl intake may exacerbate loss of body protein in µG via low grade metabolic acidosis.

Current Status of Bicarbonate in CKD

PubMed Central

Dobre, Mirela; Rahman, Mahboob

2015-01-01

Metabolic acidosis was one of the earliest complications to be recognized and explained pathologically in patients with CKD. Despite the accumulated evidence of deleterious effects of acidosis, treatment of acidosis has been tested very little, especially with respect to standard clinical outcomes. On the basis of fundamental research and small alkali supplementation trials, correcting metabolic acidosis has a strikingly broad array of potential benefits. This review summarizes the published evidence on the association between serum bicarbonate and clinical outcomes. We discuss the role of alkali supplementation in CKD as it relates to retarding kidney disease progression, improving metabolic and musculoskeletal complications. PMID:25150154

Effect of acarbose on acute acidosis.

PubMed

McLaughlin, C L; Thompson, A; Greenwood, K; Sherington, J; Bruce, C

2009-06-01

A challenge model was used to evaluate a new approach to controlling acute acidosis. Acute acidosis reduces performance in both dairy and beef cattle and most often occurs as a consequence of ingestion of large amounts of readily fermentable starch, resulting in increased production of volatile fatty acids (VFA) and lactic acid and a reduction in ruminal pH. Acarbose is an alpha-amylase and glucosidase inhibitor that slows the rate of degradation of starch to glucose, thereby reducing the rate of VFA production and maintaining rumen pH at a more stable level. It is commercially available (Glucobay, Bayer, Wuppertal, Germany) and indicated for the control of blood glucose in diabetic patients. The ability of acarbose to reduce the incidence of acidosis and the comparative efficacies of acarbose, sodium bicarbonate, and monensin were tested in 3 acute acidosis challenge experiments in cattle. Rumen-cannulated Holstein steers were challenged with a mixture of 48.4% cornstarch, 48.4% ground corn, 2.1% sodium caseinate, and 1.1% urea with or without test substance. The challenge was administered at a rate of 12.5 g/kg of body weight (BW) as a slurry through the cannula directly into the rumen. Ruminal pH was monitored at 10-min intervals throughout the study. Animals were removed from study and rumen contents replaced if they exhibited acute acidosis as defined as pH <4.5. If acidosis was not observed within 24 h, animals were subjected to a second challenge. Ruminal fluid samples were taken for measurement of VFA and lactate concentrations at various intervals after the challenge. In experiment 1, the carbohydrate challenge induced acidosis in 4 of 4 control animals and 0 of 4 animals treated with 2.14 or 21.4 mg of acarbose/kg of BW in the challenge based on the criterion of pH <4.5. In experiment 2, the carbohydrate challenge induced acidosis in 4 of 7 control animals and 1 of 7 animals when 1.07 mg of acarbose/kg of BW was included in the challenge. In experiment 3, acidosis was induced in 7 of 7 animals in the control, 1% sodium bicarbonate, and 12 mg of monensin/kg of dry matter intake groups and in 3 of 8 steers administered 1.07 mg of acarbose/kg of BW in the challenge. Increases in lactate concentrations and decreases in total VFA associated with acute acidosis were mitigated by acarbose. Thus, acarbose, an amylase and glucosidase inhibitor, prevented or reduced the incidence of acidosis in an acute challenge model in steers and was more effective than monensin or sodium bicarbonate.

Functional interaction between responses to lactic acidosis and hypoxia regulates genomic transcriptional outputs

PubMed Central

Tang, Xiaohu; Lucas, Joseph E.; Chen, Julia Ling-Yu; LaMonte, Gregory; Wu, Jianli; Wang, Michael Changsheng; Koumenis, Constantinos; Chi, Jen-Tsan

2011-01-01

Within solid tumor microenvironments, lactic acidosis and hypoxia each have powerful effects on cancer pathophysiology. However, the influence that these processes exert on each other is unknown. Here we report that a significant portion of the transcriptional response to hypoxia elicited in cancer cells is abolished by simultaneous exposure to lactic acidosis. In particular, lactic acidosis abolished stabilization of HIF-1α protein which occurs normally under hypoxic conditions. In contrast, lactic acidosis strongly synergized with hypoxia to activate the unfolded protein response (UPR) and an inflammatory response, displaying a strong similarity to ATF4-driven amino acid deprivation responses (AAR). In certain breast tumors and breast tumor cells examined, an integrative analysis of gene expression and array CGH data revealed DNA copy number alterations at the ATF4 locus, an important activator of the UPR/AAR pathway. In this setting, varying ATF4 levels influenced the survival of cells after exposure to hypoxia and lactic acidosis. Our findings reveal that the condition of lactic acidosis present in solid tumors inhibits canonical hypoxia responses and activates UPR and inflammation responses. Further, they suggest that ATF4 status may be a critical determinant of the ability of cancer cells to adapt to oxygen and acidity fluctuations in the tumor microenvironment, perhaps linking short-term transcriptional responses to long-term selection for copy number alterations in cancer cells. PMID:22135092

Bartter Syndrome Type 1 Presenting as Nephrogenic Diabetes Insipidus

PubMed Central

Fabbri, Elena; Pedini, Annalisa; Tedeschi, Silvana; Borsa, Niccolò

2018-01-01

Bartter syndrome (BS) type 1 (OMIM #601678) is a hereditary salt-losing renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypercalciuria, nephrocalcinosis, polyuria, recurrent vomiting, and growth retardation. It is caused by loss-of-function mutations of the SLC12A1 gene, encoding the furosemide-sensitive Na-K-Cl cotransporter. Recently, a phenotypic variability has been observed in patients with genetically determined BS, including absence of nephrocalcinosis, hypokalemia, and/or metabolic alkalosis in the first year of life as well as persistent metabolic acidosis mimicking distal renal tubular acidosis. We report the case of a child with a genetically determined diagnosis of Bartter syndrome type 1 who presented with a phenotype of nephrogenic diabetes insipidus, with severe hypernatremia and urinary concentrating defect. In these atypical cases, molecular analysis is mandatory to define the diagnosis, in order to establish the correct clinical and therapeutic management. PMID:29527380

Bartter Syndrome Type 1 Presenting as Nephrogenic Diabetes Insipidus.

PubMed

Vergine, Gianluca; Fabbri, Elena; Pedini, Annalisa; Tedeschi, Silvana; Borsa, Niccolò

2018-01-01

Bartter syndrome (BS) type 1 (OMIM #601678) is a hereditary salt-losing renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypercalciuria, nephrocalcinosis, polyuria, recurrent vomiting, and growth retardation. It is caused by loss-of-function mutations of the SLC12A1 gene, encoding the furosemide-sensitive Na-K-Cl cotransporter. Recently, a phenotypic variability has been observed in patients with genetically determined BS, including absence of nephrocalcinosis, hypokalemia, and/or metabolic alkalosis in the first year of life as well as persistent metabolic acidosis mimicking distal renal tubular acidosis. We report the case of a child with a genetically determined diagnosis of Bartter syndrome type 1 who presented with a phenotype of nephrogenic diabetes insipidus, with severe hypernatremia and urinary concentrating defect. In these atypical cases, molecular analysis is mandatory to define the diagnosis, in order to establish the correct clinical and therapeutic management.

β-Lapachone attenuates mitochondrial dysfunction in MELAS cybrid cells.

PubMed

Jeong, Moon Hee; Kim, Jin Hwan; Seo, Kang-Sik; Kwak, Tae Hwan; Park, Woo Jin

2014-11-21

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disease caused by mutations in the mitochondrial genome. This study investigated the efficacy of β-lapachone (β-lap), a natural quinone compound, in rescuing mitochondrial dysfunction in MELAS cybrid cells. β-Lap significantly restored energy production and mitochondrial membrane potential as well as normalized the elevated ROS level in MELAS cybrid cells. Additionally, β-lap reduced lactic acidosis and restored glucose uptake in the MELAS cybrid cells. Finally, β-lap activated Sirt1 by increasing the intracellular NAD(+)/NADH ratio, which was accompanied by increased mtDNA content. Two other quinone compounds (idebenone and CoQ10) that have rescued mitochondrial dysfunction in previous studies of MELAS cybrid cells had a minimal effect in the current study. Taken together, these results demonstrated that β-lap may provide a novel therapeutic modality for the treatment of MELAS. Copyright © 2014 Elsevier Inc. All rights reserved.

Hemolysis in a patient with alkaptonuria and chronic kidney failure.

PubMed

Heng, Anne-Elisabeth; Courbebaisse, Marie; Kemeny, Jean Louis; Matesan, Raluca; Bonniol, Claude; Deteix, Patrice; Souweine, Bertrand

2010-07-01

In alkaptonuria, the absence of homogentisic acid oxidase results in the accumulation of homogentisic acid (HGA) in the body. Fatal disease cases are infrequent, and death often results from kidney or cardiac complications. We report a 24-year-old alkaptonuric man with severe decreased kidney function who developed fatal metabolic acidosis and intravascular hemolysis. Hemolysis may have been caused by rapid and extensive accumulation of HGA and subsequent accumulation of plasma soluble melanins. Toxic effects of plasma soluble melanins, their intermediates, and reactive oxygen side products are increased when antioxidant mechanisms are overwhelmed. A decrease in serum antioxidative activity has been reported in patients with chronic decreased kidney function. However, despite administration of large doses of an antioxidant agent and ascorbic acid and intensive kidney support, hemolysis and acidosis could not be brought under control and hemolysis led to the death of the patient.

Paediatric acid-base disorders: A case-based review of procedures and pitfalls

PubMed Central

Carmody, J Bryan; Norwood, Victoria F

2013-01-01

Acid-base disorders occur frequently in paediatric patients. Despite the perception that their analysis is complex and difficult, a straightforward set of rules is sufficient to interpret even the most complex disorders – provided certain pitfalls are avoided. Using a case-based approach, the present article reviews the fundamental concepts of acid-base analysis and highlights common mistakes and oversights. Specific topics include the proper identification of the primary disorder; distinguishing compensatory changes from additional primary disorders; use of the albumin-corrected anion gap to generate a differential diagnosis for patients with metabolic acidosis; screening for mixed disorders with the delta-delta formula; recognizing the limits of compensation; use of the anion gap to identify ‘hidden’ acidosis; and the importance of using information from the history and physical examination to identify the specific cause of a patient’s acid-base disturbance. PMID:24381489

Novel 5.712 kb mitochondrial DNA deletion in a patient with Pearson syndrome: a case report.

PubMed

Park, Joonhong; Ryu, Hyejin; Jang, Woori; Chae, Hyojin; Kim, Myungshin; Kim, Yonggoo; Kim, Jiyeon; Lee, Jae Wook; Chung, Nack-Gyun; Cho, Bin; Suh, Byung Kyu

2015-05-01

Pearson marrow‑pancreas syndrome (PS) is a progressive multi‑organ disorder caused by deletions and duplications of mitochondrial DNA (mtDNA). PS is often fatal in infancy, and the majority of patients with PS succumb to the disease before reaching three‑years‑of‑age, due to septicemia, metabolic acidosis or hepatocellular insufficiency. The present report describes the case of a four‑month‑old infant with severe normocytic normochromic anemia, vacuolization of hematopoietic precursors and metabolic acidosis. After extensive clinical investigation, the patient was diagnosed with PS, which was confirmed by molecular analysis of mtDNA. The molecular analysis detected a novel large‑scale (5.712 kb) deletion spanning nucleotides 8,011 to 13,722 of mtDNA, which lacked direct repeats at the deletion boundaries. The present report is, to the best of our knowledge, the first case reported in South Korea.

[What you should know of the arterial blood gases during the watch].

PubMed

Márquez-González, Horacio; Pámanes-González, Jesús; Márquez-Flores, Horacio; Gómez-Negrete, Alonso; Muñoz-Ramírez, Mireya C; Villa-Romero, Antonio Rafael

2012-01-01

Gasometry is the measurement of dissolved gases in the blood, by measuring pH, carbon dioxide pressure (pCO(2)), serum bicarbonate (HCO(3-)), and lactate and serum electrolytes: sodium, potassium and chlorine you can make a diagnosis, etiology and treatment in the critically ill patient. The aim is to provide five steps for the interpretation of blood gases by: 1. The definition of acidemia or acidosis, or alkalemia or alkalosis. 2. Defining the metabolic component or respiratory. 3. To determine the anion gap; levels above 15 ± 2 determine other likely causes of excess anions (methanol, uremia, diabetic ketoacidosis, paraldehyde, ionized, lactic acidosis, ethylene glycol and salicylates. 4. Compensation, using the Winter formula. 5. The delta gap, with the formula for determining intrinsic and metabolic alkalosis. When anion gap is normal, is calculated urinary anion gap; the value is negative if the loss is extrarenal, contrary to the positive result is renal etiology.

The duration of time that beef cattle are fed a high-grain diet affects feed sorting behavior both before and after acute ruminal acidosis1,2.

PubMed

DeVries, T J; Schwaiger, T; Beauchemin, K A; Penner, G B

2014-04-01

The objective of this study was to determine how duration of time that cattle are fed a high-grain diet affects feed sorting, both before and after an episode of acute ruminal acidosis. Sixteen Angus heifers (261 ± 6.1 kg; BW ± SEM) were assigned to 1 of 4 blocks and fed a backgrounding (BG) diet (60% forage, DM basis). Within block, heifers were randomly assigned to 1 of 2 treatments differing in days fed a high-grain (HG; 9% forage, DM basis, fed ad libitum) diet before a ruminal acidosis challenge: 34 d for long adapted (LA) and 8 d for short adapted (SA). Ruminal acidosis was induced by restricting feed to 50% of DMI as a proportion of BW (determined individually for each heifer) for 24 h followed by an intraruminal infusion of ground barley at 10% of DMI as a proportion of BW measured before feed restriction. Feed and orts were sampled during the BG period, the first 26 d on the HG diet (only for LA cattle), the 8-d baseline (BASE) period, on the day of the ruminal acidosis challenge (CH), and during 2 consecutive 8-d recovery periods (REC1 and REC2) for each heifer and subjected to particle size analysis: 19-mm (long), 8-mm (medium), and 1.18-mm (short) screens and a pan (fine). On the BG diet, sorting for medium particles tended to be greater (104.2 vs. 102.1%; P = 0.07) for LA heifers than SA heifers, while sorting against short particles was greater (98.2 vs. 100.0%; P = 0.05) for LA heifers. During the first 26 d on the HG diet, LA cattle sorted for (P < 0.001) long (118.8%), medium (117.8%), and short (104.1%) particles and sorted against (P < 0.001) fine particles (45.3%). This sorting pattern was consistent for LA heifers during BASE period, CH day, and recovery periods, across which SA heifers exhibited less sorting (P ≤ 0.1). Greater duration of pH < 5.5 during the BASE period was associated with greater sorting for long particles (R(2) = 0.75, P = 0.01) in LA heifers and for long (R(2) = 0.49, P = 0.05) and medium (R(2) = 0.88, P < 0.001) particles in SA heifers. Long-adapted heifers linearly increased the extent of sorting for long (P = 0.007) and medium (P < 0.001) particles and against fine particles (P = 0.05) during the days following the challenge to a greater extent than SA heifers. Overall, the results demonstrate that longer-term exposure of beef heifers to a HG diet, which caused persistent low rumen pH, influenced feed sorting of heifers, both before and after an induced bout of acute ruminal acidosis, in a manner that would help attenuate the effects of acidosis.

Severe metabolic acidosis after out-of-hospital cardiac arrest: risk factors and association with outcome.

PubMed

Jamme, Matthieu; Ben Hadj Salem, Omar; Guillemet, Lucie; Dupland, Pierre; Bougouin, Wulfran; Charpentier, Julien; Mira, Jean-Paul; Pène, Frédéric; Dumas, Florence; Cariou, Alain; Geri, Guillaume

2018-05-08

Metabolic acidosis is frequently observed as a consequence of global ischemia-reperfusion after out-of-hospital cardiac arrest (OHCA). We aimed to identify risk factors and assess the impact of metabolic acidosis on outcome after OHCA. We included all consecutive OHCA patients admitted between 2007 and 2012. Using admission data, metabolic acidosis was defined by a positive base deficit and was categorized by quartiles. Main outcome was survival at ICU discharge. Factors associated with acidosis severity and with main outcome were evaluated by linear and logistic regressions, respectively. A total of 826 patients (68.3% male, median age 61 years) were included in the analysis. Median base deficit was 8.8 [5.3, 13.2] mEq/l. Male gender (p = 0.002), resuscitation duration (p < 0.001), initial shockable rhythm (p < 0.001) and post-resuscitation shock (p < 0.001) were associated with an increased level of acidosis. ICU mortality rate increased across base deficit quartiles (39.1, 59.2, 76.3 and 88.3%, p for trend < 0.001), and base deficit was independently associated with ICU mortality (p < 0.001). The proportion of CPC 1 patients among ICU survivors was similar across base deficit quartiles (72.8, 67.1, 70.5 and 62.5%, p = 0.21), and 7.3% of patients with a base deficit higher than 13.2 mEq/l survived to ICU discharge with complete neurological recovery. Severe metabolic acidosis is frequent in OHCA patients and is associated with poorer outcome, in particular due to refractory shock. However, we observed that about 7% of patients with a very severe metabolic acidosis survived to ICU discharge with complete neurological recovery.

Importance of the effective strong ion difference of an intravenous solution in the treatment of diarrheic calves with naturally acquired acidemia and strong ion (metabolic) acidosis.

PubMed

Müller, K R; Gentile, A; Klee, W; Constable, P D

2012-01-01

The effect of sodium bicarbonate on acid-base balance in metabolic acidosis is interpreted differently by Henderson-Hasselbalch and strong ion acid-base approaches. Application of the traditional bicarbonate-centric approach indicates that bicarbonate administration corrects the metabolic acidosis by buffering hydrogen ions, whereas strong ion difference theory indicates that the co-administration of the strong cation sodium with a volatile buffer (bicarbonate) corrects the strong ion acidosis by increasing the strong ion difference (SID) in plasma. To investigate the relative importance of the effective SID of IV solutions in correcting acidemia in calves with diarrhea. Twenty-two Holstein-Friesian calves (4-21 days old) with naturally acquired diarrhea and strong ion (metabolic) acidosis. Calves were randomly assigned to IV treatment with a solution of sodium bicarbonate (1.4%) or sodium gluconate (3.26%). Fluids were administered over 4 hours and the effect on acid-base balance was determined. Calves suffered from acidemia owing to moderate to strong ion acidosis arising from hyponatremia and hyper-D-lactatemia. Sodium bicarbonate infusion was effective in correcting the strong ion acidosis. In contrast, sodium gluconate infusion did not change blood pH, presumably because the strong anion gluconate was minimally metabolized. A solution containing a high effective SID (sodium bicarbonate) is much more effective in alkalinizing diarrheic calves with strong ion acidosis than a solution with a low effective SID (sodium gluconate). Sodium gluconate is ineffective in correcting acidemia, which can be explained using traditional acid-base theory but requires a new parameter, effective SID, to be understood using the strong ion approach. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Metabolic acidosis as an underlying mechanism of respiratory distress in children with severe acute asthma.

PubMed

Meert, Kathleen L; Clark, Jeff; Sarnaik, Ashok P

2007-11-01

1) To alert the clinician that increasing rate and depth of breathing during treatment of acute asthma may be a manifestation of metabolic acidosis with hyperventilation rather than worsening airway obstruction; and 2) to describe the frequency of metabolic acidosis with hyperventilation in children with severe acute asthma admitted to our pediatric intensive care unit. Retrospective medical record review. University-affiliated children's hospital. All patients admitted to the pediatric intensive care unit with a diagnosis of asthma between January 1, 2005, and December 31, 2005. None. Fifty-three patients with asthma (median age 7.8 yrs, range 0.7-17.9 yrs; 35 [66%] male; 46 [87%] black and 7 [13%] white) were admitted to the pediatric intensive care unit during the study period. Fifteen (28%) patients developed metabolic acidosis with hyperventilation (pH <7.35, Pco2 <35 torr [4.6 kPa], and base excess < or = -7 mmol/L) during their hospital course. Of these, lactic acid was assessed in four patients and was elevated in each; all had hyperglycemia (blood glucose >120 mg/dL [6.7 mmol/L]). Patients who developed metabolic acidosis with hyperventilation received asthma therapy similar to that received by patients who did not develop the disorder. Metabolic acidosis resolved contemporaneously with tapering of beta2-adrenergic agonists and administration of supportive care. All patients survived. Metabolic acidosis with hyperventilation manifesting as respiratory distress can occur in children with severe acute asthma. A pathophysiologic rationale exists for the contribution of beta2-adrenergic agents to the development of this acid-base disorder. Failure to recognize metabolic acidosis as the underlying mechanism of respiratory distress may lead to inappropriate intensification of bronchodilator therapy. Supportive care and tapering of beta2-adrenergic agents are recommended to resolve this condition.

Lactic acidosis switches cancer cells from aerobic glycolysis back to dominant oxidative phosphorylation.

PubMed

Wu, Hao; Ying, Minfeng; Hu, Xun

2016-06-28

While transformation of normal cells to cancer cells is accompanied with a switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, it is interesting to ask if cancer cells can revert from Warburg effect to OXPHOS. Our previous works suggested that cancer cells reverted to OXPHOS, when they were exposed to lactic acidosis, a common factor in tumor environment. However, the conclusion cannot be drawn unless ATP output from glycolysis and OXPHOS is quantitatively determined. Here we quantitatively measured ATP generation from glycolysis and OXPHOS in 9 randomly selected cancer cell lines. Without lactic acidosis, glycolysis and OXPHOS generated 23.7% - 52.2 % and 47.8% - 76.3% of total ATP, respectively; with lactic acidosis (20 mM lactate with pH 6.7), glycolysis and OXPHOS provided 5.7% - 13.4% and 86.6% - 94.3% of total ATP. We concluded that cancer cells under lactic acidosis reverted from Warburg effect to OXPHOS phenotype.

The effect of short-term antiorthostatic hypokinesia on central and intracardiac hemodynamics and metabolism of a healthy person

NASA Technical Reports Server (NTRS)

Katkov, V. Y.; Chesturkhin, V. V.; Zybin, O. K.; Sukhotskiy, S. S.; Abrosimov, S. V.; Utkin, V. N.

1981-01-01

The right parts of the heart and the radial artery were catheterized in healthy male volunteers before and 5 days after strict bedrest in antiorthostatic position of the body (-4.5 deg). After immobilization, most values of central circulation showed no essential changes; the only exceptions were indicates characterizing the inotropic myocardial condition. A shift in the direction of acidosis of a mixed character was noted in mixed venous blood, the beta lipoprotein content increased. A decrease in the arteriovenous difference in oxygen was encountered in blood draining from the heart (from the coronary sinus).

[Quant therapy and the composition of the moister of the eye anterior chamber (an experimental study)].

PubMed

Pavliuk, E Iu; Sherkhoeva, D Ts; Pavliuk, A Iu; Khristoforov, V N

2005-01-01

We examined 12 rabbits, 6 of whom (12 eyes) were exposed to magneto-infrared laser radiation (MILR) and another 6 (12 eyes) were controls. The parameters of pulse and continuous infrared LED radiation were as follows: wavelength--860 nm, pulse capacity--2 W, mean radiation capacity--10 mW, magnetic field strength--up to 17 mTl. A study of the moister of the anterior chamber showed a MILR-induced activated metabolism, i.e. a better acid-base balance (ABB), more intense oxygenation in the ocular tissues and decreased acidosis. Higher concentrations of buffer bases (ABEe and SBEc) cause shifts in ABB towards metabolic alkalosis. A lower concentration of glucose denotes intensified processes related with its utilization. A lack of changes in the quantity of salts in the moister of the anterior chamber rules out the possibility of that the content of glucose would go down due to its dissolution with a big volume of newly produced moister. A lack of an increase in the concentration of whole protein, as observed after MILR, can be regarded as indirect evidence to absence of any adverse effect on the vascular wall.

Evaluation of Tris-hydroxymethylaminomethane on Reversing Coagulation Abnormalities Caused by Acidosis in Pigs

DTIC Science & Technology

2007-01-01

altered whole blood. Blood 1996; 88:3432–3445 18. Butenas S, Brummel KE, Bouchard BA, et al: How factor VIIa works in hemophilia . J Thromb Haemost 2003; 1...1158–1160 19. Butenas S, Brummel KE, Branda RF, et al: Mechanism of factor VIIa-dependent coagula- tion in hemophilia blood. Blood 2002; 99: 923–930

Grain-based versus alfalfa-based subacute ruminal acidosis induction experiments: Similarities and differences between changes in milk fatty acids.

PubMed

Colman, E; Khafipour, E; Vlaeminck, B; De Baets, B; Plaizier, J C; Fievez, V

2013-07-01

Subacute ruminal acidosis (SARA) is one of the most important metabolic disorders, traditionally characterized by low rumen pH, which might be induced by an increase in the dietary proportion of grains as well as by a reduction of structural fiber. Both approaches were used in earlier published experiments in which SARA was induced by replacing part of the ration by a grain mixture or alfalfa hay by alfalfa pellets. The main differences between both experiments were the presence of blood lipopolysaccharide and Escherichia coli and associated effects on the rumen microbial population in the rumen of grain-based induced SARA animals as well as a great amount of quickly fermentable carbohydrates in the grain-based SARA induction experiment. Both induction approaches changed rumen pH although the pH decrease was more substantial in the alfalfa-based SARA induction protocol. The goal of the current analysis was to assess whether both acidosis induction approaches provoked similar shifts in the milk fatty acid (FA) profile. Similar changes of the odd- and branched-chain FA and the C18 biohydrogenation intermediates were observed in the alfalfa-based SARA induction experiment and the grain-based SARA induction experiment, although they were more pronounced in the former. The proportion of trans-10 C18:1 in the last week of the alfalfa-based induction experiment was 6 times higher than the proportion measured during the control week. The main difference between both induction experiments under similar rumen pH changes was the decreasing sum of iso FA during the grain-based SARA induction experiment whereas the sum of iso FA remained stable during the alfalfa-based SARA induction experiment. The cellulolytic bacterial community seemed to be negatively affected by either the presence of E. coli and the associated lipopolysaccharide accumulation in the rumen or by the amount of starch and quickly fermentable carbohydrates in the diet. In general, changes in the milk FA profile were related to changes in rumen pH. Nevertheless, feed characteristics (low in structural fiber vs. high in starch) also affected the milk FA profile and, as such, both effects should be taken into account when subacute acidosis occurs. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8

PubMed Central

Li, Zhigang; Dong, Lixue; Dean, Eric; Yang, Li V.

2013-01-01

Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65) is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partially rescues c-Myc expression, respectively. Acidic pH alone is insufficient to reduce c-Myc expression, as it does not decrease c-Myc in H1299 lung cancer cells expressing very low levels of pH-sensing G protein-coupled receptors (GPCRs). Instead, c-Myc is slightly increased by acidosis in H1299 cells, but this increase is completely inhibited by ectopic overexpression of TDAG8. Interestingly, TDAG8 expression is decreased by more than 50% in human lymphoma samples in comparison to non-tumorous lymph nodes and spleens, suggesting a potential tumor suppressor function of TDAG8 in lymphoma. Collectively, our results identify a novel mechanism of c-Myc regulation by acidosis in the tumor microenvironment and indicate that modulation of TDAG8 and related pH-sensing receptor pathways may be exploited as a new approach to inhibit Myc expression. PMID:24152439

Changes in the relative population size of selected ruminal bacteria following an induced episode of acidosis in beef heifers receiving viable and non-viable active dried yeast.

PubMed

Mohammed, R; Vyas, D; Yang, W Z; Beauchemin, K A

2017-06-01

To characterize the changes in the relative population size (RPS) of select ruminal bacteria and rumen fermentation variables in beef heifers supplemented with a strain of Saccharomyces cerevisiae as viable active dried (ADY) or killed dried (KDY) yeast following an induced episode of ruminal acidosis. Six ruminally cannulated beef heifers fed a diet consisting of 50% forage and 50% grain (dry matter basis) were used in a replicated 3 × 3 Latin square design with three 28-day periods. Treatments were: (i) control (CTRL; no yeast); (ii) ADY (4 g day -1 providing 10 10  CFU per g; AB Vista, UK); and (iii) KDY (4 g day -1 autoclaved ADY). The acidosis challenge was induced on day 22 and rumen samples were collected on day 15 (baseline; BASE), day 22 (challenge day; CHAL), and on day 29 (168th hour post acid challenge or recovery, REC) of each period. Over the study, duration of pH <5·8 (indicative of subacute ruminal acidosis) was less for ADY and KDY than CTRL, with ADY less than KDY. No treatment effects were observed on relative abundance of ruminal bacteria, but the day effect was significant. The RPS of lactate producers and utilizers was greater while RPS of fibrolytic bacteria was lower during CHAL than BASE and REC. Yeast supplementation, irrespective of its viability, showed beneficial effects on ruminal pH variables in animals more susceptible to acidosis. Rumen microbial population was altered with the induction of severe acidosis. Most of the changes reverted back to baseline values during the recovery phase. Yeast supplementation reduced subacute rumen acidosis in the most susceptible cattle, but failed to attenuate severe acidosis induced by a grain challenge. The study provided valuable insight into the mechanism by which acidosis affects cattle performance. Individual animal variation in ruminal fermentation partly explained the variability in response to yeast supplementation in the study. © 2017 Her Majesty the Queen in Right of Canada. Journal of Applied Microbiology © 2017 The Society for Applied Microbiology.

Improved pulmonary vascular reactivity and decreased hypertrophic remodeling during nonhypercapnic acidosis in experimental pulmonary hypertension

PubMed Central

Christou, Helen; Reslan, Ossama M.; Mam, Virak; Tanbe, Alain F.; Vitali, Sally H.; Touma, Marlin; Arons, Elena; Mitsialis, S. Alex; Kourembanas, Stella

2012-01-01

Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O2) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH4Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH4Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening, and enhances pulmonary vascular responsiveness to vasoconstrictor and vasodilator stimuli. Together with our finding that acidosis decreases VSMC proliferation, the results are consistent with the possibility that nonhypercapnic acidosis promotes differentiation of pulmonary VSMCs to a more contractile phenotype, which may enhance the effectiveness of vasodilator therapies in PH. PMID:22287610

Cholestyramine induced hyperchloremic metabolic acidosis.

PubMed

Eaves, E R; Korman, M G

1984-10-01

The first reported case, in an adult, of cholestyramine induced hyperchloremic metabolic acidosis is a 70 year old female with a two year history of primary biliary cirrhosis confirmed by histologic and immunologic criteria. After taking cholestyramine II sachets twice daily for two months she presented with lethargy, confusion and drowsiness. Examination revealed confusion, jaundice, signs of chronic liver disease, portal hypertension and hepatic encephalopathy. Laboratory investigations confirmed a metabolic acidosis (pH 7.15) and hyperchloremia. Multiple cultures failed to reveal sepsis and a urinary pH of 4.85 together with tests of renal acidification, excluded renal tubular acidosis. She received 600 mEq of sodium bicarbonate intravenously over 36 hours by which time her mentation, electrolytes and pH were normal. It is presumed that her hyperchloremic metabolic acidosis was secondary to cholestyramine because of the similarity to pediatric reports; the rapid and lasting response to intravenous sodium bicarbonate; the absence of another etiology; normal serum potassium, chloride and bicarbonate despite continued spironolactone therapy after recovery.

[5-0xoproline (pyroglutamic acid) acidosis and acetaminophen- a differential diagnosis in high anion gap metabolic acidosis].

PubMed

Weiler, Stefan; Bellmann, Romuald; Kullak-Ublick, Gerd A

2015-12-01

Rare cases of high anion gap metabolic acidosis during long-term paracetamol administration in therapeutic doses with causative 5-oxoproline (pyroglutamic acid} accumulation have been reported. Other concomitant risk factors such as malnutrition, alcohol abuse, renal or hepatic dysfunction, comedication with flue/oxacillin, vigabatrin, netilmicin or sepsis have been described. The etiology seems to be a drug-induced reversible inhibition of glutathione synthetase or 5-oxoprolinase leading to elevated serum and urine levels of 5-oxoproline. Other more frequent differential diagnoses, such as intoxications, ketoacidosis or lactic acidosis should be excluded. Causative substances should be stopped. 5-oxoproline concentrations in urine can be quantified to establish the diagnosis. Adverse drug reactions, which are not listed or insufficiently described in the respective Swiss product information, should be reported to the regional pharmacovigilance centres for early signal detection. 5-0 xoproline acidosis will be integrated as a potential adverse drug reaction in the Swiss product information for paracetamol.

Lactic acidosis switches cancer cells from aerobic glycolysis back to dominant oxidative phosphorylation

PubMed Central

Wu, Hao; Ying, Minfeng; Hu, Xun

2016-01-01

While transformation of normal cells to cancer cells is accompanied with a switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, it is interesting to ask if cancer cells can revert from Warburg effect to OXPHOS. Our previous works suggested that cancer cells reverted to OXPHOS, when they were exposed to lactic acidosis, a common factor in tumor environment. However, the conclusion cannot be drawn unless ATP output from glycolysis and OXPHOS is quantitatively determined. Here we quantitatively measured ATP generation from glycolysis and OXPHOS in 9 randomly selected cancer cell lines. Without lactic acidosis, glycolysis and OXPHOS generated 23.7% − 52.2 % and 47.8% − 76.3% of total ATP, respectively; with lactic acidosis (20 mM lactate with pH 6.7), glycolysis and OXPHOS provided 5.7% − 13.4% and 86.6% − 94.3% of total ATP. We concluded that cancer cells under lactic acidosis reverted from Warburg effect to OXPHOS phenotype. PMID:27259254

Distal renal tubular acidosis and hepatic lipidosis in a cat.

PubMed

Brown, S A; Spyridakis, L K; Crowell, W A

1986-11-15

Clinical and laboratory evidence of hepatic failure was found in a chronically anorectic cat. Simultaneous blood and urine pH determinations established a diagnosis of distal renal tubular acidosis. The cat did not respond to treatment. Necropsy revealed distal tubular nephrosis and hepatic lipidosis. The finding of distal renal tubular acidosis in a cat with hepatic lipidosis emphasizes the importance of complete evaluation of acid-base disorders in patients.

Severe lactic acidosis following alcohol related generalised seizures.

PubMed

Hulme, J; Sherwood, N

2004-12-01

A 45-year-old alcoholic man presented following several short grand-mal seizures. He was not known to be epileptic. Initial investigations demonstrated a severe lactic acidosis. The rise in lactate was one of the highest levels reported in similar patients. The patient recovered within 4 h of management with oxygen, fluids and sodium bicarbonate. Lactic acidosis following convulsions is often associated with spontaneous resolution and a favourable outcome.

Hyperammonemia associated with distal renal tubular acidosis or urinary tract infection: a systematic review.

PubMed

Clericetti, Caterina M; Milani, Gregorio P; Lava, Sebastiano A G; Bianchetti, Mario G; Simonetti, Giacomo D; Giannini, Olivier

2018-03-01

Hyperammonemia usually results from an inborn error of metabolism or from an advanced liver disease. Individual case reports suggest that both distal renal tubular acidosis and urinary tract infection may also result in hyperammonemia. A systematic review of the literature on hyperammonemia secondary to distal renal tubular acidosis and urinary tract infection was conducted. We identified 39 reports on distal renal tubular acidosis or urinary tract infections in association with hyperammonemia published between 1980 and 2017. Hyperammonemia was detected in 13 children with distal renal tubular acidosis and in one adult patient with distal renal tubular acidosis secondary to primary hyperparathyroidism. In these patients a negative relationship was observed between circulating ammonia and bicarbonate levels (P < 0.05). In 31 patients (19 children, 12 adults), an acute urinary tract infection was complicated by acute hyperammonemia and symptoms and signs of acute neuronal dysfunction, such as an altered level of consciousness, convulsions and asterixis, often associated with signs of brain edema, such as anorexia and vomiting. Urea-splitting bacteria were isolated in 28 of the 31 cases. The urinary tract was anatomically or functionally abnormal in 30 of these patients. This study reveals that both altered distal renal tubular acidification and urinary tract infection may be associated with relevant hyperammonemia in both children and adults.

Prognosis of patients presenting extreme acidosis (pH <7) on admission to intensive care unit.

PubMed

Allyn, Jérôme; Vandroux, David; Jabot, Julien; Brulliard, Caroline; Galliot, Richard; Tabatchnik, Xavier; Combe, Patrice; Martinet, Olivier; Allou, Nicolas

2016-02-01

The purpose was to determine prognosis of patients presenting extreme acidosis (pH <7) on admission to the intensive care unit (ICU) and to identify mortality risk factors. We retrospectively analyzed all patients who presented with extreme acidosis within 24 hours of admission to a polyvalent ICU in a university hospital between January 2011 and July 2013. Multivariate analysis and survival analysis were used. Among the 2156 patients admitted, 77 patients (3.6%) presented extreme acidosis. Thirty (39%) patients suffered cardiac arrest before admission. Although the mortality rate predicted by severity score was 93.6%, death occurred in 52 cases (67.5%) in a median delay of 13 (5-27) hours. Mortality rate depended on reason for admission, varying between 22% for cases linked to diabetes mellitus and 100% for cases of mesenteric infarction (P = .002), cardiac arrest before admission (P < .001), type of lactic acidosis (P = .007), high Simplified Acute Physiology Score II (P = .008), and low serum creatinine (P = .012). Patients with extreme acidosis on admission to ICU have a less severe than expected prognosis. Whereas mortality is almost 100% in cases of cardiac arrest before admission, mortality is much lower in the absence of cardiac arrest before admission, which justifies aggressive ICU therapies. Copyright © 2015 Elsevier Inc. All rights reserved.

Acid-base alterations in heatstroke.

PubMed

Bouchama, A; De Vol, E B

2001-04-01

To analyze the acid-base balance during heatstroke. Retrospective study. Heatstroke Center, Makkah, Saudi Arabia. Hundred nine consecutive heatstroke patients (mean age 55 +/- 12 years) with rectal temperature from 40 to 43.4 degrees C following exposure to hot weather. Arterial blood gases collected prospectively and analyzed using 95% confidence limits established by controlled experimental studies. Severity of heatstroke on admission assessed by Simplified Acute Physiology Score and Organ System Failure score. Metabolic acidosis was the predominant acid-base change followed by respiratory alkalosis (81 and 55% of the patients, respectively). The prevalence of metabolic acidosis (but not respiratory alkalosis) was significantly associated with the degree of hyperthermia: 63, 95 and 100% at 41, 42 and 43 degrees C, respectively (p < 0.0001). Patients with metabolic acidosis had a large anion gap (24 +/- 5). Arterial partial pressure of oxygen (PaO2), systolic blood pressure and Organ System Failure score were similar with or without metabolic acidosis. Although the acute physiology score was higher in patients with, than without, metabolic acidosis (15.7 +/- 3.7 vs 9.8 +/- 4.4, p < 0.001), there was no significant difference in neurologic morbidity and mortality (7.9 vs 1.1%, 5.6 vs 0%, p = 0.776 and 0.581, respectively). We conclude that metabolic acidosis is the predominant response in heatstroke.

Coagulopathy induced by acidosis, hypothermia and hypocalcaemia in severe bleeding.

PubMed

De Robertis, E; Kozek-Langenecker, S A; Tufano, R; Romano, G M; Piazza, O; Zito Marinosci, G

2015-01-01

Acidosis, hypothermia and hypocalcaemia are determinants for morbidity and mortality during massive hemorrhages. However, precise pathological mechanisms of these environmental factors and their potential additive or synergistic anticoagulant and/or antiplatelet effects are not fully elucidated and are at least in part controversial. Best available evidences from experimental trials indicate that acidosis and hypothermia progressively impair platelet aggregability and clot formation. Considering the cell-based model of coagulation physiology, hypothermia predominantly prolongs the initiation phase, while acidosis prolongs the propagation phase of thrombin generation. Acidosis increases fibrinogen breakdown while hypothermia impairs its synthesis. Acidosis and hypothermia have additive effects. The effect of hypocalcaemia on coagulopathy is less investigated but it appears that below the cut-off of 0.9 mmol/L, several enzymatic steps in the plasmatic coagulation system are blocked while above that cut-off effects remain without clinical sequalae. The impact of environmental factor on hemostasis is underestimated in clinical practice due to our current practice of using routine coagulation laboratory tests such as partial thromboplastin time or prothrombin time, which are performed at standardized test temperature, after pH correction, and upon recalcification. Temperature-adjustments are feasible in viscoelastic point-of-care tests such as thrombelastography and thromboelastometry which may permit quantification of hypothermia-induced coagulopathy. Rewarming hypothermic bleeding patients is highly recommended because it improves patient outcome. Despite the absence of high-quality evidence, calcium supplementation is clinical routine in bleeding management. Buffer administration may not reverse acidosis-induced coagulopathy but may be essential for the efficacy of coagulation factor concentrates such as recombinant activated factor VII.

Clinical and molecular aspects of distal renal tubular acidosis in children.

PubMed

Besouw, Martine T P; Bienias, Marc; Walsh, Patrick; Kleta, Robert; Van't Hoff, William G; Ashton, Emma; Jenkins, Lucy; Bockenhauer, Detlef

2017-06-01

Distal renal tubular acidosis (dRTA) is characterized by hyperchloraemic metabolic acidosis, hypokalaemia, hypercalciuria and nephrocalcinosis. It is due to reduced urinary acidification by the α-intercalated cells in the collecting duct and can be caused by mutations in genes that encode subunits of the vacuolar H + -ATPase (ATP6V1B1, ATP6V0A4) or the anion exchanger 1 (SLC4A1). Treatment with alkali is the mainstay of therapy. This study is an analysis of clinical data from a long-term follow-up of 24 children with dRTA in a single centre, including a genetic analysis. Of the 24 children included in the study, genetic diagnosis was confirmed in 19 patients, with six children having mutations in ATP6V1B1, ten in ATP6V0A4 and three in SLC4A1; molecular diagnosis was not available for five children. Five novel mutations were detected (2 in ATP6V1B1 and 3 in ATP6V0A4). Two-thirds of patients presented with features of proximal tubular dysfunction leading to an erroneous diagnosis of renal Fanconi syndrome. The proximal tubulopathy disappeared after resolution of acidosis, indicating the importance of following proximal tubular function to establish the correct diagnosis. Growth retardation with a height below -2 standard deviation score was found in ten patients at presentation, but persisted in only three of these children once established on alkali treatment. Sensorineural hearing loss was found in five of the six patients with an ATP6V1B1 mutation. Only one patient with an ATP6V0A4 mutation had sensorineural hearing loss during childhood. Nine children developed medullary cysts, but without apparent clinical consequences. Cyst development in this cohort was not correlated with age at therapy onset, molecular diagnosis, growth parameters or renal function. In general, the prognosis of dRTA is good in children treated with alkali.

Long-term low-dose glucocorticoid therapy associated with remission of overt renal tubular acidosis in Sjögren's syndrome.

PubMed

el-Mallakh, R S; Bryan, R K; Masi, A T; Kelly, C E; Rakowski, K J

1985-10-01

Renal tubular acidosis and focal interstitial inflammatory cell infiltrate secondary to Sjögren's syndrome remitted with low-dose glucocorticoid therapy over five and one half years in a patient with associated mild systemic lupus erythematosus. Such response has not been previously documented. This observation may have therapeutic applications for renal tubular acidosis associated with Sjögren's syndrome that deserve further investigation.

Mechanisms of CO2/H+ chemoreception by respiratory rhythm generator neurons in the medulla from newborn rats in vitro.

PubMed

Kawai, Akira; Onimaru, Hiroshi; Homma, Ikuo

2006-04-15

We investigated mechanisms of CO(2)/H(+) chemoreception in the respiratory centre of the medulla by measuring membrane potentials of pre-inspiratory neurons, which are putative respiratory rhythm generators, in the brainstem-spinal cord preparation of the neonatal rat. Neuronal response was tested by changing superfusate CO(2) concentration from 2% to 8% at constant HCO(3)(-) concentration (26 mm) or by changing pH from 7.8 to 7.2 by reducing HCO(3)(-) concentration at constant CO(2) (5%). Both respiratory and metabolic acidosis lead to depolarization of neurons with increased excitatory synaptic input and increased burst rate. Respiratory acidosis potentiated the amplitude of the neuronal drive potential. In the presence of tetrodotoxin (TTX), membrane depolarization persisted during respiratory and metabolic acidosis. However, the depolarization was smaller than that before application of TTX, which suggests that some neurons are intrinsically, and others synaptically, chemosensitive to CO(2)/H(+). Application of Ba(2+) blocked membrane depolarization by respiratory acidosis, whereas significant depolarization in response to metabolic acidosis still remained after application of Cd(2+) and Ba(2+). We concluded that the intrinsic responses to CO(2)/H(+)changes were mediated by potassium channels during respiratory acidosis, and that some other mechanisms operate during metabolic acidosis. In low-Ca(2+), high-Mg(2+) solution, an increased CO(2) concentration induced a membrane depolarization with a simultaneous increase of the burst rate. Pre-inspiratory neurons could adapt their baseline membrane potential to external CO(2)/H(+) changes by integration of these mechanisms to modulate their burst rates. Thus, pre-inspiratory neurons might play an important role in modulation of respiratory rhythm by central chemoreception in the brainstem-spinal cord preparation.

Influence of acidosis on cardiotonic effects of colforsin and epinephrine: a dose-response study.

PubMed

Hagiya, Keiichi; Takahashi, Hiroshi; Isaka, Yumi; Inomata, Shinichi; Tanaka, Makoto

2013-10-01

Acidosis produces a negative inotropic effect on cardiac muscle against which catecholamines and phosphodiesterase III inhibitors have limited therapeutic effects. This study evaluated the effects of colforsin, which directly activates adenylate cyclase without β-adrenergic receptor activation, in isolated Langendorff rat hearts in a pH- and concentration-dependent manner. Experimental animal study. A university laboratory. Sprague-Dawley rats. Hearts were isolated and perfused with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid/Tyrode solution (pH 7.4) in the Langendorff preparation. The hearts were assigned randomly to the control (pH 7.4), mild acidosis (pH 7.0), or severe acidosis (pH 6.6) group (n = 8 per group) and were perfused continuously with colforsin 10(-7), 10(-6), and 10(-5) mol/L. Maximum dP/dt was determined, and the concentration-response relation was evaluated at each pH. Colforsin at 10(-6) mol/L increased the maximum dP/dt from 2,592 ± 557 to 5,189 ± 721 mmHg/s (p < 0.001) and from 1,942 ± 325 to 3,399 ± 608 mmHg/s (p < 0.001) in the control and mild acidosis groups, respectively; whereas colforsin, 10(-5) mol/L, significantly increased the maximum dP/dt even in the severe acidosis group. No significant difference was seen in maximum dP/dt among the 3 groups after infusion with colforsin 10(-5) mol/L. In contrast to catecholamines and other inodilators, colforsin at a high concentration restores decreased cardiac contractility against severe acidosis to an extent similar to physiologic pH. Copyright © 2013 Elsevier Inc. All rights reserved.

Nasal flaring as a clinical sign of respiratory acidosis in patients with dyspnea.

PubMed

Zorrilla-Riveiro, José Gregorio; Arnau-Bartés, Anna; Rafat-Sellarés, Ramón; García-Pérez, Dolors; Mas-Serra, Arantxa; Fernández-Fernández, Rafael

2017-04-01

To determine whether the presence of nasal flaring is a clinical sign of respiratory acidosis in patients attending emergency departments for acute dyspnea. Single-center, prospective, observational study of patients aged over 15 requiring urgent attention for dyspnea, classified as level II or III according to the Andorran Triage Program and who underwent arterial blood gas test on arrival at the emergency department. The presence of nasal flaring was evaluated by two observers. Demographic and clinical variables, signs of respiratory difficulty, vital signs, arterial blood gases and clinical outcome (hospitalization and mortality) were recorded. Bivariate and multivariate analyses were performed using logistic regression models. The sample comprised 212 patients, mean age 78years (SD=12.8), of whom 49.5% were women. Acidosis was recorded in 21.2%. Factors significantly associated with the presence of acidosis in the bivariate analysis were the need for pre-hospital medical care, triage level II, signs of respiratory distress, presence of nasal flaring, poor oxygenation, hypercapnia, low bicarbonates and greater need for noninvasive ventilation. Nasal flaring had a positive likelihood ratio for acidosis of 4.6 (95% CI 2.9-7.4). In the multivariate analysis, triage level II (aOR 5.16; 95% CI: 1.91 to 13.98), the need for oxygen therapy (aOR 2.60; 95% CI: 1.13-5.96) and presence of nasal flaring (aOR 6.32; 95% CI: 2.78-14.41) were maintained as factors independently associated with acidosis. Nasal flaring is a clinical sign of severity in patients requiring urgent care for acute dyspnea, which has a strong association with acidosis and hypercapnia. Copyright © 2016 Elsevier Inc. All rights reserved.

Mechanisms of CO2/H+ chemoreception by respiratory rhythm generator neurons in the medulla from newborn rats in vitro

PubMed Central

Kawai, Akira; Onimaru, Hiroshi; Homma, Ikuo

2006-01-01

We investigated mechanisms of CO2/H+ chemoreception in the respiratory centre of the medulla by measuring membrane potentials of pre-inspiratory neurons, which are putative respiratory rhythm generators, in the brainstem–spinal cord preparation of the neonatal rat. Neuronal response was tested by changing superfusate CO2 concentration from 2% to 8% at constant HCO3− concentration (26 mm) or by changing pH from 7.8 to 7.2 by reducing HCO3− concentration at constant CO2 (5%). Both respiratory and metabolic acidosis lead to depolarization of neurons with increased excitatory synaptic input and increased burst rate. Respiratory acidosis potentiated the amplitude of the neuronal drive potential. In the presence of tetrodotoxin (TTX), membrane depolarization persisted during respiratory and metabolic acidosis. However, the depolarization was smaller than that before application of TTX, which suggests that some neurons are intrinsically, and others synaptically, chemosensitive to CO2/H+. Application of Ba2+ blocked membrane depolarization by respiratory acidosis, whereas significant depolarization in response to metabolic acidosis still remained after application of Cd2+ and Ba2+. We concluded that the intrinsic responses to CO2/H+changes were mediated by potassium channels during respiratory acidosis, and that some other mechanisms operate during metabolic acidosis. In low-Ca2+, high-Mg2+ solution, an increased CO2 concentration induced a membrane depolarization with a simultaneous increase of the burst rate. Pre-inspiratory neurons could adapt their baseline membrane potential to external CO2/H+ changes by integration of these mechanisms to modulate their burst rates. Thus, pre-inspiratory neurons might play an important role in modulation of respiratory rhythm by central chemoreception in the brainstem–spinal cord preparation. PMID:16469786

Comparisons of Normal Saline and Lactated Ringer’s Resuscitation on Hemodynamics, Metabolic Responses, and Coagulation in Pigs after Severe Hemorrhagic Shock

DTIC Science & Technology

2013-12-11

vasodilator effects and the risks of metabolic acidosis and hyperkalemia . Keywords: Hemorrhagic shock, Oxygen metabolism, Coagulation, Pre-hospital...www.sjtrem.com/content/21/1/86 of hyperchloremic acidosis from NS resuscitation [37]. Consistent with our current results, clinically significant hyperkalemia ...risks of meta- bolic acidosis and hyperkalemia . Currently, military first responders have NS, LR and Hextend available [20]. How- ever, the results from

Low sensitivity of anion gap to detect clinically significant lactic acidosis in the emergency department.

PubMed

Xu, Q; HowlettClyne, S; Fuezery, A; Cembrowski, G S

2017-12-01

Lactic acidosis represents the pathologic accumulation of lactate and hydrogen ions. It is important to efficiently diagnose lactic acidosis as delayed treatment will lead to poor patient outcomes. As plasma lactate levels may not be rapidly available, some physicians may use elevated anion gaps to test for the need to measure lactate. All Edmonton metropolitan hospitals have Radiometer blood gas/electrolyte instruments in the ED or close by. As lactate is measured for each set of electrolytes, we were able to determine the effectiveness of a screening anion gap for lactic acidosis. Two years of emergency department lactates and electrolytes from Edmonton's 5 metropolitan hospitals were analyzed. We determined the sensitivity, specificity and positive predictive value of detecting an elevated lactate, defined as ≥2.5mmol/L or ≥4mmol/L. Depending on the elevated anion gap cut-off and the definition of elevated lactate, between 40-80% of elevated lactates are missed. In general, the positive predictive value approaches 40% for AGs ≥12mmol/L and 60% for AGs ≥16mmol/L. Anion gap is an inadequate marker of lactic acidosis. We recommend that lactate be done with each set of electrolytes and/or blood gases. In this way lactic acidosis will not be missed. Copyright © 2017. Published by Elsevier Inc.

Osteomalacia complicating renal tubular acidosis in association with Sjogren's syndrome.

PubMed

El Ati, Zohra; Fatma, Lilia Ben; Boulahya, Ghada; Rais, Lamia; Krid, Madiha; Smaoui, Wided; Maiz, Hedi Ben; Beji, Soumaya; Zouaghi, Karim; Moussa, Fatma Ben

2014-09-01

Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA), which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L), hypophosphatemia (0.4 mmol/L), hypocalcemia (2.14 mmol/L) and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L). The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7), glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer's test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®), calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

Anaerobic threshold: review of the concept and directions for future research.

PubMed

Davis, J A

1985-02-01

Although the term anaerobic threshold was introduced 20 years ago, the concept that an exercise-induced lactic acidosis occurs at a particular oxygen uptake which varies among subjects is over 50 years old. The surge of new interest in the parameter relates to its strong relationship to prolonged exercise performance. The average marathon running speed has been shown to be closely related to the running speed at the anaerobic threshold. Numerous studies have shown that the parameter can be validly measured during incremental exercise from the gas exchange consequences of the increased carbon dioxide and hydrogen ion levels in blood resulting from bicarbonate buffering of lactic acid. Refinement of the noninvasive detection scheme has made the parameter attractive to investigators in preventative, rehabilitative, and occupational medicine and to researchers in the exercise sciences. Controversy exists regarding the specific cause for the onset of exercise-induced metabolic acidosis. As experimentation continues to unravel the mechanisms of lactate production and ventilatory control during exercise, the anaerobic threshold concept can be further evaluated.

Acute renal response to rapid onset respiratory acidosis.

PubMed

Ramadoss, Jayanth; Stewart, Randolph H; Cudd, Timothy A

2011-03-01

Renal strong ion compensation to chronic respiratory acidosis has been established, but the nature of the response to acute respiratory acidosis is not well defined. We hypothesized that the response to acute respiratory acidosis in sheep is a rapid increase in the difference in renal fractional excretions of chloride and sodium (Fe(Cl) - Fe(Na)). Inspired CO(2) concentrations were increased for 1 h to significantly alter P(a)CO(2) and pH(a) from 32 ± 1 mm Hg and 7.52 ± 0.02 to 74 ± 2 mm Hg and 7.22 ± 0.02, respectively. Fe(Cl) - Fe(Na) increased significantly from 0.372 ± 0.206 to 1.240 ± 0.217% and returned to baseline at 2 h when P(a)CO(2) and pH(a) were 37 ± 0.6 mm Hg and 7.49 ± 0.01, respectively. Arterial pH and Fe(Cl) - Fe(Na) were significantly correlated. We conclude that the kidney responds rapidly to acute respiratory acidosis, within 30 min of onset, by differential reabsorption of sodium and chloride.

Seizure Termination by Acidosis Depends on ASIC1a

PubMed Central

Ziemann, Adam E.; Schnizler, Mikael K.; Albert, Gregory W.; Severson, Meryl A.; Howard, Matthew A.; Welsh, Michael J.; Wemmie, John A.

2008-01-01

SUMMARY Most seizures stop spontaneously. However, the molecular mechanisms remain unknown. Earlier observations that seizures reduce brain pH and that acidosis inhibits seizures indicated that acidosis halts epileptic activity. Because acid–sensing ion channel–1a (ASIC1a) shows exquisite sensitivity to extracellular pH and regulates neuron excitability, we hypothesized that acidosis might activate ASIC1a to terminate seizures. Disrupting mouse ASIC1a increased the severity of chemoconvulsant–induced seizures, whereas overexpressing ASIC1a had the opposite effect. ASIC1a did not affect seizure threshold or onset, but shortened seizure duration and prevented progression. CO2 inhalation, long known to lower brain pH and inhibit seizures, also required ASIC1a to interrupt tonic–clonic seizures. Acidosis activated inhibitory interneurons through ASIC1a, suggesting that ASIC1a might limit seizures by increasing inhibitory tone. These findings identify ASIC1a as a key element in seizure termination when brain pH falls. The results suggest a molecular mechanism for how the brain stops seizures and suggest new therapeutic strategies. PMID:18536711

Third ventricle choroid plexus function and its response to acute perturbations in plasma chemistry.

PubMed

Harbut, R E; Johanson, C E

1986-05-21

The homeostatic role of the third ventricle choroid plexus (3VCP) in the maintenance of CSF electrolytes was investigated by quantifying alterations in CP epithelial ion concentrations induced by chemical perturbations of plasma in adult Sprague-Dawley rats. Significant regional differences (third vs fourth (4VCP) and lateral ventricle CP (LVCP] were found in epithelial content of Na+ and K+, with respect to baseline levels as well as alterations caused by 5-60 min of systemic metabolic acidosis. 3VCP, which comprises ca. 10% of total choroidal tissue, has a water content, extracellular fluid volume and vascularity comparable to 4VCP and LVCP; yet 3VCP is characterized by relatively high and low values for cellular [Na+] (68 mM) and [K+] (118 mM). Compared to time-matched controls, acute metabolic acidosis (i.p. NH4Cl) effected a response, i.e. increases [K+] and decreases [Na+], in 3VCP that was less than in 4VCP, and substantially smaller than in LVCP. The onset and duration of induced electrolyte changes were qualitatively similar among the 3 plexus regions. Although systemic acidosis severely altered CP electrolyte concentrations, it did not compromise CSF homeostasis of [K+] and [Na+]. The function of 3VCP is discussed in terms of secretory capacity, embryological origin, and innervation. Overall, the findings indicate that transport/permeability phenomena which mediate transmembrane distribution of Na+ and K+ in 3VCP differ quantitatively from other regions of the blood-CSF barrier.

Neem oil poisoning: Case report of an adult with toxic encephalopathy.

PubMed

Mishra, Ajay; Dave, Nikhil

2013-09-01

Neem oil has widespread use in Indian subcontinent due to its many bioactive properties. Azadirachtin, an active ingredient, is implicated in causing the effects seen in neem oil poisoning. Neem oil poisoning is rare in adults. This report highlights the toxicity associated with neem oil poisoning in an elderly male. The patient presented with vomiting, seizures, metabolic acidosis, and toxic encephalopathy. The patient recovered completely with symptomatic treatment.

Late onset MELAS with m.3243A > G mutation and its association with aneurysm formation.

PubMed

Zhu, Kun; Li, Shuang; Chen, Huan; Wang, Yao; Yu, Miao; Wang, Hongyan; Zhao, Weijie; Cao, Yunpeng

2017-08-01

We reported a 53-year-old with late-onset mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) accompanied by aneurysm and large vessel dilations. Most studies have focused on microangiopathy causing stroke-like episodes. We report a case to describe large vessel involvement in clinical considerations, and possible mechanisms of aneurysm formation. We recommended regular angiographic examination for patients with MELAS.

Acute cyanide toxicity caused by apricot kernel ingestion.

PubMed

Suchard, J R; Wallace, K L; Gerkin, R D

1998-12-01

A 41-year-old woman ingested apricot kernels purchased at a health food store and became weak and dyspneic within 20 minutes. The patient was comatose and hypothermic on presentation but responded promptly to antidotal therapy for cyanide poisoning. She was later treated with a continuous thiosulfate infusion for persistent metabolic acidosis. This is the first reported case of cyanide toxicity from apricot kernel ingestion in the United States since 1979.

Metabolic acidosis in short bowel syndrome: think D-lactic acid acidosis.

PubMed

Stanciu, Sorin; De Silva, Aminda

2018-05-16

Short bowel syndrome (SBS) is a condition when a person's gastrointestinal function is insufficient to supply the body with essential nutrients and hydration. Patients with SBS suffer from diarrhoea and symptoms of malabsorption such as weight loss, electrolyte disturbances and vitamin deficiencies. Long-term management of this condition can be complicated by the underlying disease, the abnormal bowel function and issues related to treatment like administration of parenteral nutrition and the use of a central venous catheter. Here, we describe a case of D-lactic acid acidosis, a rarer complication of SBS, presenting with generalised weakness and severe metabolic acidosis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[MELAS: Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes].

PubMed

Murakami, Hidetomo; Ono, Kenjiro

2017-02-01

Mitochondrial disease is caused by a deficiency in the energy supply to cells due to mitochondrial dysfunction. Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a mitochondrial disease that presents with stroke-like episodes such as acute onset of neurological deficits and characteristic imaging findings. Stroke-like episodes in MELAS have the following features: 1) neurological deficits due to localization of lesions in the brain, 2) episodes often accompany epilepsy, 3) lesions do not follow the vascular supply area, 4) lesions are more often seen in the posterior brain than in the anterior brain, 5) lesions spread to an adjacent area in the brain, and 6) neurological symptoms often disappear together with imaging findings, but later relapse. About 80% of patients with MELAS have an A-to-G transition mutation at the nucleotide pair 3243 in the dihydrouridine loop of mitochondrial tRNA^Leu(UUR), which causes the absence of posttranscriptional taurine modification at the wobble nucleotide of mitochondrial tRNA^Leu(UUR) and disrupts protein synthesis. However, the precise pathophysiology of stroke-like episodes is under investigation, with possible hypotheses for these episodes including mitochondrial angiopathy, mitochondrial cytopathy, and neuron-astrocyte uncoupling. With regard to treatment, L-arginine and taurine have recently been suggested for relief of clinical symptoms.

The duration of time that beef cattle are fed a high-grain diet affects the recovery from a bout of ruminal acidosis: dry matter intake and ruminal fermentation.

PubMed

Schwaiger, T; Beauchemin, K A; Penner, G B

2013-12-01

This study was conducted to determine if the duration of time cattle are fed a high-grain diet affects their susceptibility to and recovery from ruminal acidosis. Sixteen Angus heifers (BW ± SEM, 261 ± 6.1 kg) were assigned to 1 of 4 blocks and fed a backgrounding diet consisting of 60% barley silage, 30% barley grain, and 10% supplement (DM basis). Within block, cattle were randomly assigned to 1 of 2 treatments differing in the number of days they were fed the high-grain diet before an acidosis challenge: 34 d for long adapted (LA) and 8 d for short adapted (SA). All heifers were exposed to the same 20 d dietary transition to a high-grain diet containing 9% barley silage, 81% barley grain, and 10% supplement (DM basis). Ruminal acidosis was induced by restricting feed to 50% of DMI:BW for 24 h followed by an intraruminal infusion of ground barley at 10% DMI:BW. Heifers were then given their regular diet allocation 1 h after the intraruminal infusion. Data were collected during an 8-d baseline period (BASE), on the day of the acidosis challenge (CHAL), and during 2 consecutive 8-d recovery periods (REC1 and REC2). Acidosis induction increased daily duration (531 to 1,020 min/d; P < 0.001) and area (176 to 595 (min × pH)/d; P < 0.001) that ruminal pH was <5.5 relative to BASE. Relative to BASE, inducing acidosis also increased the daily mean (0.3 to 11.4 mM; P = 0.013) and maximum (1.3 to 29.3 mM; P = 0.008) ruminal fluid lactate concentrations. There was no effect of dietary treatment on ruminal pH, lactate, or short-chain fatty acid (SCFA) concentrations (P > 0.050). However, during BASE and CHAL, SA heifers experienced greater linear (P = 0.031), quadratic (P = 0.016), and cubic (P = 0.008) coefficients for the duration of time that pH was <5.5. In addition, a treatment × day interaction for the duration that pH was <5.5 during REC1 suggested that LA cattle tended to recover from the challenge more rapidly than SA cattle (P = 0.085). Regression analysis confirmed that the LA heifers experienced a quicker linear (P = 0.019) recovery from induced acidosis over time. These results indicate adaptation of the ruminal epithelium continues with advancing time as evidenced by more stable ruminal pH both before and after an induced bout of acute ruminal acidosis but does not affect susceptibility of cattle to ruminal acidosis.

Acidosis and Correction of Acidosis Does Not Affect rFVIIa Function in Swine

DTIC Science & Technology

2012-12-15

and its correction (or normalization of pH) has been suggested before clinical use of rFVIIa [21, 22]. FVII is one of the many coagulation factors ...A or B (deficient in Factor VIII and Factor IX). Mice lacking FVII die in-utero or soon after birth due to vascular and hemostatic defects [23...the activity of recombinant activated Factor VII (rFVIIa) in vitro. However, it is not known if acidosis induced by hemorrhagic shock or infusion of

Acid-Base Disorders in Patients with Chronic Obstructive Pulmonary Disease: A Pathophysiological Review

PubMed Central

Bruno, Cosimo Marcello; Valenti, Maria

2012-01-01

The authors describe the pathophysiological mechanisms leading to development of acidosis in patients with chronic obstructive pulmonary disease and its deleterious effects on outcome and mortality rate. Renal compensatory adjustments consequent to acidosis are also described in detail with emphasis on differences between acute and chronic respiratory acidosis. Mixed acid-base disturbances due to comorbidity and side effects of some drugs in these patients are also examined, and practical considerations for a correct diagnosis are provided. PMID:22500110

A Bovine Hemoglobin-Based Oxygen Carrier as Pump Prime for Cardiopulmonary Bypass: Reduced Systemic Lactic Acidosis and Improved Cerebral Oxygen Metabolism During Low-flow in a Porcine Model

DTIC Science & Technology

2010-11-10

1 A bovine hemoglobin-based oxygen carrier as pump prime for cardiopulmonary bypass: reduced systemic lactic acidosis and improved cerebral...2010 2. REPORT TYPE Final Report 3. DATES COVERED (From - To) June 2007 - November 2010 4. TITLE AND SUBTITLE A bovine hemoglobin-based oxygen...carrier as pump prime for cardiopulmonary bypass: reduced systemic lactic acidosis and improved cerebral oxygen metabolism during low-flow in a

Ischemic-Anoxia of the Central Nervous System: Iron Dependent Oxidative Injury during Reperfusion.

DTIC Science & Technology

1986-10-15

much deeper tissue acidosis and augmented injury is seen in contrast to complete ischemic-anoxia. 4 8. The delocalized iron catalyzes the production of...of deep metabolic acidosis (HCO5 at about 10 meq/L). OCCM maintained good oxygenation, ventilation and acid base balance. The blood gas differences to...lactic acidosis which occurs in the brain under the influence of such low flow rates. 4 3. Siesjo’s study of the pH dependence of lipid peroxidation in

Effects of C1 Inhibitor on Tissue Damage in a Porcine Model of Controlled Hemorrhage

DTIC Science & Technology

2012-07-01

and cytokine release and improves metabolic acidosis in a porcine model of hemorrhagic shock. Male Yorkshire swine were assigned to experimental groups...damage in a dose-dependent man- ner (100 and 250 IU/kg). In addition, rhC1-INH (250 IU/kg) markedly improved hemorrhage-induced metabolic acidosis ... acidosis , reduced circulating tumor necrosis factor !, and attenuated tissue damage in this model. The observed beneficial effects of rhC1-INH treatment on

Effect of extracellular acid–base disturbances on the intracellular pH of neurones cultured from rat medullary raphe or hippocampus

PubMed Central

Bouyer, Patrice; Bradley, Stefania Risso; Zhao, Jinhua; Wang, Wengang; Richerson, George B; Boron, Walter F

2004-01-01

Previous reports suggest that an important characteristic of chemosensitive neurones is an unusually large change of steady-state intracellular pH in response to a change in extracellular pH (ΔpHi/ΔpHo). To determine whether such a correlation exists between neurones from the medullary raphe (a chemosensitive brain region) and hippocampus (a non-chemosensitive region), we used BCECF to monitor pHi in cultured neurones subjected to extracellular acid–base disturbances. In medullary raphe neurones, respiratory acidosis (5% → 9% CO2) caused a rapid fall in pHi (ΔpHi ∼0.2) with no recovery and a large ΔpHi/ΔpHo of 0.71. Hippocampal neurones had a similar response, but with a slightly lower ΔpHi/ΔpHo (0.59). We further investigated a possible link between pHi regulation and chemosensitivity by following the pHi measurements on medullary raphe neurones with an immunocytochemistry for tryptophan hydroxylase (a marker of serotonergic neurones). We found that the ΔpHi/ΔpHo of 0.69 for serotonergic neurones (which are stimulated by acidosis) was not different from either the ΔpHi/ΔpHo of 0.75 for non-serotonergic neurones (most of which are not chemosensitive), or from the ΔpHi/ΔpHo of hippocampal neurones. For both respiratory alkalosis (5% → 3% CO2) and metabolic alkalosis (22 mm → 35 mm HCO3−), ΔpHi/ΔpHo was 0.42–0.53 for all groups of neurones studied. The only notable difference between medullary raphe and hippocampal neurones was in response to metabolic acidosis (22 mm → 14 mm HCO3−), which caused a large pHi decrease in ∼80% of medullary raphe neurones (ΔpHi/ΔpHo = 0.71), but relatively little pHi decrease in 70% of the hippocampal neurones (ΔpHi/ΔpHo = 0.09). Our comparison of medullary raphe and hippocampal neurones indicates that, except in response to metabolic acidosis, the neurones from the chemosensitive region do not have a uniquely high ΔpHi/ΔpHo. Moreover, regardless of whether neurones were cultured from the chemosensitive or the non-chemosensitive region, pHi did not recover during any of the acid–base stresses. PMID:15194736

Nicotinamide Riboside and Mitochondrial Biogenesis

ClinicalTrials.gov

2018-03-15

Mitochondrial Diseases; Mitochondrial Myopathies; Progressive External Ophthalmoplegia; Progressive Ophthalmoplegia; Progressive; Ophthalmoplegia, External; Mitochondria DNA Deletion; MELAS; Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes; Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome)

Epimural Indicator Phylotypes of Transiently-Induced Subacute Ruminal Acidosis in Dairy Cattle

PubMed Central

Wetzels, Stefanie U.; Mann, Evelyne; Metzler-Zebeli, Barbara U.; Pourazad, Poulad; Qumar, Muhammad; Klevenhusen, Fenja; Pinior, Beate; Wagner, Martin; Zebeli, Qendrim; Schmitz-Esser, Stephan

2016-01-01

The impact of a long-term subacute rumen acidosis (SARA) on the bovine epimural bacterial microbiome (BEBM) and its consequences for rumen health is poorly understood. This study aimed to investigate shifts in the BEBM during a long-term transient SARA model consisting of two concentrate-diet-induced SARA challenges separated by a 1-week challenge break. Eight cows were fed forage and varying concentrate amounts throughout the experiment. In total, 32 rumen papilla biopsies were taken for DNA isolation (4 sampling time points per cow: at the baseline before concentrate was fed, after the first SARA challenge, after the challenge break, and after the second SARA challenge). Ruminal pH was continuously monitored. The microbiome was determined using Illumina MiSeq sequencing of the 16S rRNA gene (V345 region). In total 1,215,618 sequences were obtained and clustered into 6833 operational taxonomic units (OTUs). Campylobacter and Kingella were the most abundant OTUs (16.5 and 7.1%). According to ruminal pH dynamics, the second challenge was more severe than the first challenge. Species diversity estimates and evenness increased during the challenge break compared to all other sampling time points (P < 0.05). During both SARA challenges, Kingella- and Azoarcus-OTUs decreased (0.5 and 0.4 fold-change) and a dominant Ruminobacter-OTU increased during the challenge break (18.9 fold-change; P < 0.05). qPCR confirmed SARA-related shifts. During the challenge break noticeably more OTUs increased compared to other sampling time points. Our results show that the BEBM re-establishes the baseline conditions slower after a SARA challenge than ruminal pH. Key phylotypes that were reduced during both challenges may help to establish a bacterial fingerprint to facilitate understanding effects of SARA conditions on the BEBM and their consequences for the ruminant host. PMID:26973642

Epimural Indicator Phylotypes of Transiently-Induced Subacute Ruminal Acidosis in Dairy Cattle.

PubMed

Wetzels, Stefanie U; Mann, Evelyne; Metzler-Zebeli, Barbara U; Pourazad, Poulad; Qumar, Muhammad; Klevenhusen, Fenja; Pinior, Beate; Wagner, Martin; Zebeli, Qendrim; Schmitz-Esser, Stephan

2016-01-01

The impact of a long-term subacute rumen acidosis (SARA) on the bovine epimural bacterial microbiome (BEBM) and its consequences for rumen health is poorly understood. This study aimed to investigate shifts in the BEBM during a long-term transient SARA model consisting of two concentrate-diet-induced SARA challenges separated by a 1-week challenge break. Eight cows were fed forage and varying concentrate amounts throughout the experiment. In total, 32 rumen papilla biopsies were taken for DNA isolation (4 sampling time points per cow: at the baseline before concentrate was fed, after the first SARA challenge, after the challenge break, and after the second SARA challenge). Ruminal pH was continuously monitored. The microbiome was determined using Illumina MiSeq sequencing of the 16S rRNA gene (V345 region). In total 1,215,618 sequences were obtained and clustered into 6833 operational taxonomic units (OTUs). Campylobacter and Kingella were the most abundant OTUs (16.5 and 7.1%). According to ruminal pH dynamics, the second challenge was more severe than the first challenge. Species diversity estimates and evenness increased during the challenge break compared to all other sampling time points (P < 0.05). During both SARA challenges, Kingella- and Azoarcus-OTUs decreased (0.5 and 0.4 fold-change) and a dominant Ruminobacter-OTU increased during the challenge break (18.9 fold-change; P < 0.05). qPCR confirmed SARA-related shifts. During the challenge break noticeably more OTUs increased compared to other sampling time points. Our results show that the BEBM re-establishes the baseline conditions slower after a SARA challenge than ruminal pH. Key phylotypes that were reduced during both challenges may help to establish a bacterial fingerprint to facilitate understanding effects of SARA conditions on the BEBM and their consequences for the ruminant host.

Maternally inherited Leigh syndrome: an unusual cause of infantile apnea.

PubMed

Shuk-kuen Chau, Christy; Kwok, Ka-li; Ng, Daniel K; Lam, Ching-Wan; Tong, Sui-Fan; Chan, Yan-Wo; Siu, Wai-Kwan; Yuen, Yuet-Ping

2010-06-01

Leigh Syndrome is an uncommon cause of infantile apnea. We report a 5-month-old girl with sudden respiratory arrest followed by episodic hyper- and hypo-ventilation, encephalopathy, and persistent lactic acidosis. Computed tomography of the brain revealed symmetric low densities over the basal ganglia, internal capsule, thalami, and midbrain. Cardiac echocardiogram was suggestive of hypertrophic cardiomyopathy. Diagnosis of Leigh syndrome due to T8993G mutation was confirmed with polymerase chain reaction and direct DNA sequencing of mitochondrial genome. To our knowledge, this is the first report of proven maternally inherited Leigh syndrome in Hong Kong.

Obscure Severe Infrarenal Aortoiliac Stenosis With Severe Transient Lactic Acidosis

PubMed Central

Nantsupawat, Teerapat; Mankongpaisarnrung, Charoen; Soontrapa, Suthipong; Limsuwat, Chok

2013-01-01

A 57-year-old man presented with sudden onset of leg pain, right-sided weakness, aphasia, confusion, drooling, and severe lactic acidosis (15 mmol/L). He had normal peripheral pulses and demonstrated no pain, pallor, poikilothermia, paresthesia, or paralysis. Empiric antibiotics, aspirin, full-dose enoxaparin, and intravenous fluid were initiated. Lactic acid level decreased to 2.5 mmol/L. The patient was subsequently extubated and was alert and oriented with no complaints of leg or abdominal pain. Unexpectedly, the patient developed cardiac arrest, rebound severe lactic acidosis (8.13 mmol/L), and signs of acute limb ischemia. Emergent computed tomography of the aorta confirmed infrarenal aortoiliac thrombosis. Transient leg pain and transient severe lactic acidosis can be unusual presentations of severe infrarenal aortoiliac stenosis. When in doubt, vascular studies should be implemented without delay to identify this catastrophic diagnosis. PMID:26425569

An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy.

PubMed

Yuen, Alan W C; Walcutt, Isabel A; Sander, Josemir W

2017-09-01

Diets that increase production of ketone bodies to provide alternative fuel for the brain are evolving from the classic ketogenic diet for epilepsy devised nearly a century ago. The classic ketogenic diet and its more recent variants all appear to have similar efficacy with approximately 50% of users showing a greater than 50% seizure reduction. They all require significant medical and dietetic support, and there are tolerability issues. A review suggests that low-grade chronic metabolic acidosis associated with ketosis is likely to be an important contributor to the short term and long term adverse effects of ketogenic diets. Recent studies, particularly with the characterization of the acid sensing ion channels, suggest that chronic metabolic acidosis may increase the propensity for seizures. It is also known that low-grade chronic metabolic acidosis has a broad range of negative health effects and an increased risk of early mortality in the general population. The modified ketogenic dietary treatment we propose is formulated to limit acidosis by measures that include monitoring protein intake and maximizing consumption of alkaline mineral-rich, low carbohydrate green vegetables. We hypothesize that this acidosis-sparing ketogenic diet is expected to be associated with less adverse effects and improved efficacy. A case history of life-long intractable epilepsy shows this diet to be a successful long-term strategy but, clearly, clinical studies are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Outcomes of Extremely Low Birth Weight Infants with Acidosis at Birth

PubMed Central

Randolph, David A.; Nolen, Tracy L.; Ambalavanan, Namasivayam; Carlo, Waldemar A.; Peralta-Carcelen, Myriam; Das, Abhik; Bell, Edward F.; Davis, Alexis S.; Laptook, Abbot R.; Stoll, Barbara J.; Shankaran, Seetha; Higgins, Rosemary D.

2014-01-01

OBJECTIVES To test the hypothesis that acidosis at birth is associated with the combined primary outcome of death or neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants, and to develop a predictive model of death/NDI exploring perinatal acidosis as a predictor variable. STUDY DESIGN The study population consisted of ELBW infants born between 2002-2007 at NICHD Neonatal Research Network hospitals. Infants with cord blood gas data and documentation of either mortality prior to discharge or 18-22 month neurodevelopmental outcomes were included. Multiple logistic regression analysis was used to determine the contribution of perinatal acidosis, defined as a cord blood gas with a pH<7 or base excess (BE)<-12, to death/NDI in ELBW infants. In addition, a multivariable model predicting death/NDI was developed. RESULTS 3979 patients were identified of whom 249 had a cord gas pH<7 or BE<-12 mEq/L. 2124 patients (53%) had the primary outcome of death/NDI. After adjustment for confounding variables, pH<7 and BE<-12 mEq/L were each significantly associated with death/NDI (OR=2.5[1.6,4.2]; and OR=1.5[1.1,2.0], respectively). However, inclusion of pH or BE did not improve the ability of the multivariable model to predict death/NDI. CONCLUSIONS Perinatal acidosis is significantly associated with death/NDI in ELBW infants. Perinatal acidosis is infrequent in ELBW infants, however, and other factors are more important in predicting death/NDI. PMID:24554564

Augmentation of poly(ADP-ribose) polymerase-dependent neuronal cell death by acidosis.

PubMed

Zhang, Jian; Li, Xiaoling; Kwansa, Herman; Kim, Yun Tai; Yi, Liye; Hong, Gina; Andrabi, Shaida A; Dawson, Valina L; Dawson, Ted M; Koehler, Raymond C; Yang, Zeng-Jin

2017-06-01

Tissue acidosis is a key component of cerebral ischemic injury, but its influence on cell death signaling pathways is not well defined. One such pathway is parthanatos, in which oxidative damage to DNA results in activation of poly(ADP-ribose) polymerase and generation of poly(ADP-ribose) polymers that trigger release of mitochondrial apoptosis-inducing factor. In primary neuronal cultures, we first investigated whether acidosis per sé is capable of augmenting parthanatos signaling initiated pharmacologically with the DNA alkylating agent, N-methyl- N'-nitro- N-nitrosoguanidine. Exposure of neurons to medium at pH 6.2 for 4 h after N-methyl- N'-nitro- N-nitrosoguanidine washout increased intracellular calcium and augmented the N-methyl- N'-nitro- N-nitrosoguanidine-evoked increase in poly(ADP-ribose) polymers, nuclear apoptosis-inducing factor , and cell death. The augmented nuclear apoptosis-inducing factor and cell death were blocked by the acid-sensitive ion channel-1a inhibitor, psalmotoxin. In vivo, acute hyperglycemia during transient focal cerebral ischemia augmented tissue acidosis, poly(ADP-ribose) polymers formation, and nuclear apoptosis-inducing factor , which was attenuated by a poly(ADP-ribose) polymerase inhibitor. Infarct volume from hyperglycemic ischemia was decreased in poly(ADP-ribose) polymerase 1-null mice. Collectively, these results demonstrate that acidosis can directly amplify neuronal parthanatos in the absence of ischemia through acid-sensitive ion channel-1a . The results further support parthanatos as one of the mechanisms by which ischemia-associated tissue acidosis augments cell death.

Bicarbonate sensing in mouse cortical astrocytes during extracellular acid/base disturbances.

PubMed

Theparambil, Shefeeq M; Naoshin, Zinnia; Defren, Sabrina; Schmaelzle, Jana; Weber, Tobias; Schneider, Hans-Peter; Deitmer, Joachim W

2017-04-15

The present study suggests that the electrogenic sodium-bicarbonate cotransporter, NBCe1, supported by carbonic anhydrase II, CAII, provides an efficient mechanism of bicarbonate sensing in cortical astrocytes. This mechanism is proposed to play a major role in setting the pH i responses to extracellular acid/base challenges in astrocytes. A decrease in extracellular [HCO 3 - ] during isocapnic acidosis and isohydric hypocapnia, or an increase in intracellular [HCO 3 - ] during hypercapnic acidosis, was effectively sensed by NBCe1, which carried bicarbonate out of the cells under these conditions, and caused an acidification and sodium fall in WT astrocytes, but not in NBCe1-knockout astrocytes. Isocapnic acidosis, hypercapnic acidosis and isohydric hypocapnia evoked inward currents in NBCe1- and CAII-expressing Xenopus laevis oocytes, but not in native oocytes, suggesting that NBCe1 operates in the outwardly directed mode under these conditions consistent with our findings in astrocytes. We propose that bicarbonate sensing of astrocytes may have functional significance during extracellular acid/base disturbances in the brain, as it not only alters intracellular pH/[HCO 3 - ]-dependent functions of astrocytes, but also modulates the extracellular pH/[HCO 3 - ] in brain tissue. Extracellular acid/base status of the mammalian brain undergoes dynamic changes during many physiological and pathological events. Although intracellular pH (pH i ) of astrocytes responds to extracellular acid/base changes, the mechanisms mediating these changes have remained unresolved. We have previously shown that the electrogenic sodium-bicarbonate cotransporter, NBCe1, is a high-affinity bicarbonate carrier in cortical astrocytes. In the present study, we investigated whether NBCe1 plays a role in bicarbonate sensing in astrocytes, and in determining the pH i responses to extracellular acid/base challenges. We measured changes in intracellular H + and Na + in astrocytes from wild-type (WT) and from NBCe1-knockout (KO) mice, using ion-selective dyes, during isocapnic acidosis, hypercapnic acidosis and hypocapnia. We also analysed NBCe1-mediated membrane currents in Xenopus laevis oocytes under similar conditions. Comparing WT and NBCe1-KO astrocytes, we could dissect the contribution of NBCe1, of diffusion of CO 2 across the cell membrane and, after blocking carbonic anhydrase (CA) activity with ethoxyzolamide, of the role of CA, for the amplitude and rate of acid/base fluxes. Our results suggest that NBCe1 transport activity in astrocytes, supported by CA activity, renders astrocytes bicarbonate sensors in the mouse cortex. NBCe1 carried bicarbonate into and out of the cell by sensing the variations of transmembrane [HCO 3 - ], irrespective of the changes in intra- and extracellular pH, and played a major role in setting pH i responses to the extracellular acid/base challenges. We propose that bicarbonate sensing of astrocytes may have potential functional significance during extracellular acid/base alterations in the brain. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Bicarbonate sensing in mouse cortical astrocytes during extracellular acid/base disturbances

PubMed Central

Naoshin, Zinnia; Defren, Sabrina; Schmaelzle, Jana; Weber, Tobias; Schneider, Hans‐Peter

2017-01-01

Key points The present study suggests that the electrogenic sodium–bicarbonate cotransporter, NBCe1, supported by carbonic anhydrase II, CAII, provides an efficient mechanism of bicarbonate sensing in cortical astrocytes. This mechanism is proposed to play a major role in setting the pHi responses to extracellular acid/base challenges in astrocytes.A decrease in extracellular [HCO3 −] during isocapnic acidosis and isohydric hypocapnia, or an increase in intracellular [HCO3 −] during hypercapnic acidosis, was effectively sensed by NBCe1, which carried bicarbonate out of the cells under these conditions, and caused an acidification and sodium fall in WT astrocytes, but not in NBCe1‐knockout astrocytes.Isocapnic acidosis, hypercapnic acidosis and isohydric hypocapnia evoked inward currents in NBCe1‐ and CAII‐expressing Xenopus laevis oocytes, but not in native oocytes, suggesting that NBCe1 operates in the outwardly directed mode under these conditions consistent with our findings in astrocytes.We propose that bicarbonate sensing of astrocytes may have functional significance during extracellular acid/base disturbances in the brain, as it not only alters intracellular pH/[HCO3 −]‐dependent functions of astrocytes, but also modulates the extracellular pH/[HCO3 −] in brain tissue. Abstract Extracellular acid/base status of the mammalian brain undergoes dynamic changes during many physiological and pathological events. Although intracellular pH (pHi) of astrocytes responds to extracellular acid/base changes, the mechanisms mediating these changes have remained unresolved. We have previously shown that the electrogenic sodium–bicarbonate cotransporter, NBCe1, is a high‐affinity bicarbonate carrier in cortical astrocytes. In the present study, we investigated whether NBCe1 plays a role in bicarbonate sensing in astrocytes, and in determining the pHi responses to extracellular acid/base challenges. We measured changes in intracellular H+ and Na+ in astrocytes from wild‐type (WT) and from NBCe1‐knockout (KO) mice, using ion‐selective dyes, during isocapnic acidosis, hypercapnic acidosis and hypocapnia. We also analysed NBCe1‐mediated membrane currents in Xenopus laevis oocytes under similar conditions. Comparing WT and NBCe1‐KO astrocytes, we could dissect the contribution of NBCe1, of diffusion of CO2 across the cell membrane and, after blocking carbonic anhydrase (CA) activity with ethoxyzolamide, of the role of CA, for the amplitude and rate of acid/base fluxes. Our results suggest that NBCe1 transport activity in astrocytes, supported by CA activity, renders astrocytes bicarbonate sensors in the mouse cortex. NBCe1 carried bicarbonate into and out of the cell by sensing the variations of transmembrane [HCO3 −], irrespective of the changes in intra‐ and extracellular pH, and played a major role in setting pHi responses to the extracellular acid/base challenges. We propose that bicarbonate sensing of astrocytes may have potential functional significance during extracellular acid/base alterations in the brain. PMID:27981578

Neem oil poisoning: Case report of an adult with toxic encephalopathy

PubMed Central

Mishra, Ajay; Dave, Nikhil

2013-01-01

Neem oil has widespread use in Indian subcontinent due to its many bioactive properties. Azadirachtin, an active ingredient, is implicated in causing the effects seen in neem oil poisoning. Neem oil poisoning is rare in adults. This report highlights the toxicity associated with neem oil poisoning in an elderly male. The patient presented with vomiting, seizures, metabolic acidosis, and toxic encephalopathy. The patient recovered completely with symptomatic treatment. PMID:24339648

More than meets the eye: infant presenting with hypoxic ischaemic encephalopathy.

PubMed

Sen, Kuntal; Agarwal, Rajkumar

2018-04-05

We report a newborn infant who presented with poor Apgar scores and umbilical artery acidosis leading to the diagnosis of hypoxic ischaemic encephalopathy. During the course of the infant's hospitalisation, subsequent workup revealed an underlying genetic cause that masqueraded as hypoxic ischaemic encephalopathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Distal Renal Tubular Acidosis in Infancy: A Bicarbonate Wasting State

ERIC Educational Resources Information Center

Rodriguez-Soriano, J.; And Others

1975-01-01

Studied were three unrelated infants with distal renal tubular acidosis (a condition characterized by an inability to acidify the urine to minimal pH levels resulting in the loss of bicarbonates). (DB)

[Alcoholic ketoacidosis and reversible neurological complications due to hypophosphataemia].

PubMed

Fernández López, Ma T; García Bargo, Ma D; Rivero Luis, Ma T; Álvarez Vázquez, P; Saenz Fernández, C A; Mato Mato, J A

2012-01-01

A 57-year-old man with chronic alcoholism was admitted to our hospital due to disturbance of consciousness and polyradiculitis. Laboratory examination revealed metabolic acidosis, hypokalemia and hypophosphataemia. Alcoholic ketoacidosis is a common disorder in alcoholic patients. All patients present with a history of heavy alcohol misuse, preceding a bout of particularly excesive intake, which had been terminated by nausea, vomiting and abdominal pain. The most important laboratory results are: normal or low glucose level, metabolic acidosis with a raised anion GAP, low or absent blood alcohol level and urinary ketones. The greatest threats to patients are: hypovolemia, hypokaliemia, hypoglucemia and acidosis. Alcohol abuse may result in a wide range of electrolyte and acid-base disorders including hypophosphataemia, hypomagnesemia, hypocalcemia, hypokalemia, metabolic acidosis and respiratory alkalosis. Disturbance of consciousness in alcoholic patients is observed in several disorders, such drunkenness, Wernicke encephalopathy, alcohol withdrawal syndrome, central pontine myelinolysis, hepatic encephalopathy, hypoglucemia and electrolyte disorders.

A STUDY OF THE ACIDOSIS, BLOOD UREA, AND PLASMA CHLORIDES IN URANIUM NEPHRITIS IN THE DOG, AND OF THE PROTECTIVE ACTION OF SODIUM BICARBONATE.

PubMed

Goto, K

1917-05-01

1. The presence of an acidosis in dogs with experimental uranium nephritis is demonstrable by the Van Slyke-Stillman-Cullen method and that of Marriott. It is detected more readily by the former method. 2. This acidosis is associated with increase in the blood urea and plasma chlorides and with the appearance of albumin and casts in the urine. 3. The oral administration of sodium bicarbonate diminishes the acidosis, the increase in plasma chlorides, the amount of albumin and casts in the urine, and, to a lesser degree, the increase in the blood urea following the administration of uranium. It also diminishes the severity of the changes produced by uranium in the kidneys. 4. The oral administration of sodium bicarbonate to normal dogs raises the carbon dioxide content of the plasma as determined by the. Van Slyke-Stillman-Cullen method.

Missense mutation T485S alters NBCe1-A electrogenicity causing proximal renal tubular acidosis

PubMed Central

Shao, Xuesi M.; Kao, Liyo; Azimov, Rustam; Weinstein, Alan M.; Newman, Debra; Liu, Weixin; Kurtz, Ira

2013-01-01

Mutations in SLC4A4, the gene encoding the electrogenic Na+-HCO3− cotransporter NBCe1, cause severe proximal renal tubular acidosis (pRTA), growth retardation, decreased IQ, and eye and teeth abnormalities. Among the known NBCe1 mutations, the disease-causing mechanism of the T485S (NBCe1-A numbering) mutation is intriguing because the substituted amino acid, serine, is structurally and chemically similar to threonine. In this study, we performed intracellular pH and whole cell patch-clamp measurements to investigate the base transport and electrogenic properties of NBCe1-A-T485S in mammalian HEK 293 cells. Our results demonstrated that Ser substitution of Thr485 decreased base transport by ∼50%, and importantly, converted NBCe1-A from an electrogenic to an electroneutral transporter. Aqueous accessibility analysis using sulfhydryl reactive reagents indicated that Thr485 likely resides in an NBCe1-A ion interaction site. This critical location is also supported by the finding that G486R (a pRTA causing mutation) alters the position of Thr485 in NBCe1-A thereby impairing its transport function. By using NO3− as a surrogate ion for CO32−, our result indicated that NBCe1-A mediates electrogenic Na+-CO32− cotransport when functioning with a 1:2 charge transport stoichiometry. In contrast, electroneutral NBCe1-T485S is unable to transport NO3−, compatible with the hypothesis that it mediates Na+-HCO3− cotransport. In patients, NBCe1-A-T485S is predicted to transport Na+-HCO3− in the reverse direction from blood into proximal tubule cells thereby impairing transepithelial HCO3− absorption, possibly representing a new pathogenic mechanism for generating human pRTA. PMID:23636456

Acidosis slows the response of oxidative phosphorylation to metabolic demand in isolated rabbit heart.

PubMed

Hak, J B; van Beek, J H; Westerhof, N

1993-05-01

The purpose of this study was to investigate the effect of acidosis on the mean response time of mitochondrial oxygen consumption to steps in heart rate and in left ventricular balloon volume. The mean response time may be viewed as the average delay between a change in adenosine triphosphate (ATP) hydrolysis and oxygen consumption. The mean response time is calculated by subtracting the transport time, required for diffusion of oxygen and for convective transport through the coronary vessels, from the response time measured in the coronary venous effluent. Eight isolated rabbit hearts were perfused according to Langendorff using Tyrode solution at 28 degrees C. Arterial perfusate pH was lowered from 7.30 +/- 0.03 (mean +/- SD) to 6.59 +/- 0.02 by increasing the CO2 tension. At pH 7.3 the mean response time was 12.6 +/- 1.6 s, independent of the time after isolation of the heart. During acidosis, applied 40-75 min after isolation of the heart, the mean response time was 21.4 +/- 0.7 s and increased to 32.6 +/- 4.3 s during acidosis, 85-120 min after isolation. Thus the retardation of the metabolic response by acidosis might depend on the condition of the heart. A decrease of mitochondrial ATP synthetic capacity during acidosis may contribute to the retardation of the metabolic response. Since determination of the mean response time at 37 degrees C is not yet feasible, the experiments were done at 28 degrees C. Extrapolation of our findings to 37 degrees C appears premature.

Association of metabolic acidosis with bovine milk-based human milk fortifiers.

PubMed

Cibulskis, C C; Armbrecht, E S

2015-02-01

To compare the incidence of metabolic acidosis and feeding intolerance associated with powdered or acidified liquid human milk fortifier (HMF). This retrospective study evaluated infants ⩽ 32 weeks gestational age or ⩽ 1500 g birth weight who received human milk with either powdered or acidified liquid HMF (50 consecutively born infants per group). Primary outcomes tracked were metabolic acidosis (base excess less than -4 mmol l(-1) or bicarbonate less than 18 mmol l(-1)), feeding intolerance (gastric residual > 50% feed volume, > 3 loose stools or emesis per day, abdominal tenderness or distention), necrotizing enterocolitis, late-onset infection, death, length of hospital stay and ability to remain on HMF. Demographics, feeding practices, growth parameters and laboratory data were also collected. Significantly more infants who received acidified liquid HMF developed metabolic acidosis (P < 0.001). Base excess and bicarbonate were both significantly decreased after HMF addition in the liquid HMF group (base excess P = 0.006, bicarbonate P < 0.001). More infants were switched off liquid HMF due to metabolic acidosis or feeding intolerance than those on powdered HMF (P < 0.001). Despite increased protein intake in the liquid HMF group (P = 0.009), both groups had similar enteral caloric intakes with no difference in growth rates between the two groups. There was no significant difference in any of the other primary outcomes. Infants receiving acidified liquid human milk fortifier were more likely to develop metabolic acidosis and to be switched off HMF than those who received powdered HMF. Growth in the liquid HMF group was no different than the powdered group, despite higher protein intake.

Metabolic acidosis in neonatal calf diarrhea-clinical findings and theoretical assessment of a simple treatment protocol.

PubMed

Trefz, F M; Lorch, A; Feist, M; Sauter-Louis, C; Lorenz, I

2012-01-01

Clinical assessment of metabolic acidosis in calves with neonatal diarrhea can be difficult because increased blood concentrations of d-lactate and not acidemia per se are responsible for most of the clinical signs exhibited by these animals. To describe the correlation between clinical and laboratory findings and d-lactate concentrations. Furthermore, the theoretical outcome of a simplified treatment protocol based on posture/ability to stand and degree of dehydration was evaluated. A total of 121 calves with diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital during an 8-month study period. Prospective blinded cohort study. Physical examinations were carried out following a standardized protocol. Theoretical outcome of treatment was calculated. Type and degree of metabolic acidosis were age dependent. The clinical parameters posture, behavior, and palpebral reflex were closely correlated to base excess (r = 0.74, 0.78, 0.68; P < .001) and d-lactate concentrations (r = 0.59, 0.59, 0.71; P < .001), respectively. Thus, determining the degree of loss of the palpebral reflex was identified as the best clinical tool for diagnosing increase in serum d-lactate concentrations. Theoretical outcome of treatment revealed that the tested dosages of sodium bicarbonate are more likely to overdose than to underdose calves with diarrhea and metabolic acidosis. The degree of metabolic acidosis in diarrheic calves can be predicted based on clinical findings. The assessed protocol provides a useful tool to determine bicarbonate requirements, but a revision is necessary for calves with ability to stand and marked metabolic acidosis. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Ca++-sensitizing mutations in troponin, Pi, and 2-deoxyATP alter the depressive effect of acidosis on regulated thin-filament velocity

PubMed Central

Longyear, Thomas J.; Turner, Matthew A.; Davis, Jonathan P.; Lopez, Joseph; Biesiadecki, Brandon

2014-01-01

Repeated, intense contractile activity compromises the ability of skeletal muscle to generate force and velocity, resulting in fatigue. The decrease in velocity is thought to be due, in part, to the intracellular build-up of acidosis inhibiting the function of the contractile proteins myosin and troponin; however, the underlying molecular basis of this process remains poorly understood. We sought to gain novel insight into the decrease in velocity by determining whether the depressive effect of acidosis could be altered by 1) introducing Ca++-sensitizing mutations into troponin (Tn) or 2) by agents that directly affect myosin function, including inorganic phosphate (Pi) and 2-deoxy-ATP (dATP) in an in vitro motility assay. Acidosis reduced regulated thin-filament velocity (VRTF) at both maximal and submaximal Ca++ levels in a pH-dependent manner. A truncated construct of the inhibitory subunit of Tn (TnI) and a Ca++-sensitizing mutation in the Ca++-binding subunit of Tn (TnC) increased VRTF at submaximal Ca++ under acidic conditions but had no effect on VRTF at maximal Ca++ levels. In contrast, both Pi and replacement of ATP with dATP reversed much of the acidosis-induced depression of VRTF at saturating Ca++. Interestingly, despite producing similar magnitude increases in VRTF, the combined effects of Pi and dATP were additive, suggesting different underlying mechanisms of action. These findings suggest that acidosis depresses velocity by slowing the detachment rate from actin but also by possibly slowing the attachment rate. PMID:24651988

The choice of dialysate bicarbonate: do different concentrations make a difference?

PubMed

Basile, Carlo; Rossi, Luigi; Lomonte, Carlo

2016-05-01

Metabolic acidosis is a common complication of chronic kidney disease; it is typically caused by the accumulation of sulfate, phosphorus, and organic anions. Metabolic acidosis is correlated with several adverse outcomes, such as morbidity, hospitalization, and mortality. Thus, correction of metabolic acidosis is fundamental for the adequate management of many systemic complications of chronic kidney disease. In patients undergoing hemodialysis, acid-base homeostasis depends on many factors including the following: net acid production, amount of alkali given by the dialysate bath, duration of the interdialytic period, and residual diuresis, if any. Recent literature data suggest that the development of metabolic alkalosis after dialysis may contribute to adverse clinical outcomes. Our review is focused on the potential effects of different dialysate bicarbonate concentrations on hard outcomes such as mortality. Unfortunately, no randomized studies exist about this issue. Acid-base equilibrium is a complex and vital system whose regulation is impaired in chronic kidney disease. We await further studies to assess the extent to which acid-base status is a major determinant of overall survival in patients undergoing hemodialysis. For the present, the clinician should understand that target values for predialysis serum bicarbonate concentration have been established primarily based on observational studies and expert opinion. Based on this, we should keep the predialysis serum bicarbonate level at least at 22 mmol/l. Furthermore, a specific focus should be addressed by the attending nephrologist to the clinical and nutritional status of the major outliers on both the acid and alkaline sides of the curve. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Haploinsufficiency of the ammonia transporter Rhcg predisposes to chronic acidosis: Rhcg is critical for apical and basolateral ammonia transport in the mouse collecting duct.

PubMed

Bourgeois, Soline; Bounoure, Lisa; Christensen, Erik I; Ramakrishnan, Suresh K; Houillier, Pascal; Devuyst, Olivier; Wagner, Carsten A

2013-02-22

Ammonia secretion by the collecting duct (CD) is critical for acid-base homeostasis and, when defective, causes distal renal tubular acidosis (dRTA). The Rhesus protein RhCG mediates NH(3) transport as evident from cell-free and cellular models as well as from Rhcg-null mice. Here, we investigated in a Rhcg mouse model the metabolic effects of Rhcg haploinsufficiency, the role of Rhcg in basolateral NH(3) transport, and the mechanisms of adaptation to the lack of Rhcg. Both Rhcg(+/+) and Rhcg(+/-) mice were able to handle an acute acid load, whereas Rhcg(-/-) mice developed severe metabolic acidosis with reduced ammonuria and high mortality. However, chronic acid loading revealed that Rhcg(+/-) mice did not fully recover, showing lower blood HCO(3)(-) concentration and more alkaline urine. Microperfusion studies demonstrated that transepithelial NH(3) permeability was reduced by 80 and 40%, respectively, in CDs from Rhcg(-/-) and Rhcg(+/-) mice compared with controls. Basolateral membrane permeability to NH(3) was reduced in CDs from Rhcg(-/-) mice consistent with basolateral Rhcg localization. Rhcg(-/-) responded to acid loading with normal expression of enzymes and transporters involved in proximal tubular ammoniagenesis but reduced abundance of the NKCC2 transporter responsible for medullary accumulation of ammonium. Consequently, tissue ammonium content was decreased. These data demonstrate a role for apical and basolateral Rhcg in transepithelial NH(3) transport and uncover an incomplete dRTA phenotype in Rhcg(+/-) mice. Haploinsufficiency or reduced expression of RhCG may underlie human forms of (in)complete dRTA.

Functional characterization of transmembrane intracellular pH regulators and mechanism of alcohol-induced intracellular acidosis in human umbilical cord blood stem cell-like cells.

PubMed

Tsai, Yi-Ting; Liu, Jah-Yao; Lee, Chung-Yi; Tsai, Chien-Sung; Chen, Ming-Hurng; Ou, Chien-Chih; Chen, Wei-Hwa; Loh, Shih-Hurng

2011-12-01

Changing intracellular pH (pHi) exerts considerable influence on many cellular functions. Different pHi regulators, such as the Na-H exchanger (NHE), Na/(Equation is included in full-text article.)symporter, and Cl/OH exchanger (CHE), have been identified in mature mammalian cells. The aims of the present study were to investigate the physiological mechanisms of pHi recovery and to further explore the effects of alcohol on the pHi in human umbilical cord blood CD34 stem cell-like cells (HUCB-CD34STs). HUCB-CD34STs were loaded with the pH-sensitive dye, 2',7'-bis(2-carboxethyl)-5(6)-carboxyfluorescein, to examine pHi. In isolated HUCB-CD34STs, we found that (1) the resting pHi is 7.03 ± 0.02; (2) 2 Na-dependent acid extruders and a Cl-dependent acid loading carrier exist and are functional; (3) alcohol functions in a concentration-dependent manner to reduce pHi and increase NHE activity, but it does not affect CHE activity; and (4) fomepizole, a specific alcohol dehydrogenase inhibitor, does not change the intracellular acidosis and NHE activity-induced by alcohol, whereas 3-amino-1, 2,4-trizole, a specific catalase inhibitor, entirely abolishes these effects. In conclusion, we demonstrate that 2 acid extruders and 1 acid loader (most likely NHE, NBC, and CHE, respectively) functionally existed in HUCB-CD34STs. Additionally, the intracellular acidosis is mainly caused by catalase-mediated alcohol metabolites, which provoke the activity of NHE.

An autopsy case of death due to metabolic acidosis after citric acid ingestion.

PubMed

Ikeda, Tomoya; Usui, Akihito; Matsumura, Takashi; Aramaki, Tomomi; Hosoya, Tadashi; Igari, Yui; Ohuchi, Tsukasa; Hayashizaki, Yoshie; Usui, Kiyotaka; Funayama, Masato

2015-11-01

A man in his 40s was found unconscious on a sofa in a communal residence for people with various disabilities. He appeared to have drunk 800 ml of undiluted citric acid from a commercial plastic bottle. The instructions on the label of the beverage specified that the beverage be diluted 20- to 30-fold before consumption. The patient was admitted to an emergency hospital with severe metabolic acidosis (pH, 6.70; HCO3(-), 3.6 mEq/L) and a low ionized calcium level (0.73 mmol/L). Although ionized calcium and catecholamines were continuously administered intravenously to correct the acidosis, the state of acidemia and low blood pressure did not improve, and he died 20 h later. Citric acid concentrations in the patient's serum drawn shortly after treatment in the hospital and from the heart at autopsy were 80.6 mg/ml and 39.8 mg/dl, respectively (normal range: 1.3-2.6 mg/dl). Autopsy revealed black discoloration of the mucosal surface of the esophagus. Microscopically, degenerated epithelium and neutrophilic infiltration in the muscle layer were observed. In daily life, drinking a large amount of concentrated citric acid beverage is rare as a cause of lethal poisoning. However, persons with mental disorders such as dementia may mistakenly drink detergent or concentrated fluids, as in our case. Family members or facility staff in the home or nursing facility must bear in mind that they should not leave such bottles in places where they are easily accessible to mentally handicapped persons. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of respiratory alkalosis and acidosis on myocardial blood flow and metabolism in patients with coronary artery disease.

PubMed

Kazmaier, S; Weyland, A; Buhre, W; Stephan, H; Rieke, H; Filoda, K; Sonntag, H

1998-10-01

Variation of the arterial carbon dioxide partial pressure (PaCO2) is not uncommon in anesthetic practice. However, little is known about the myocardial consequences of respiratory alkalosis and acidosis, particularly in patients with coronary artery disease. The aim of the current study was to investigate the effects of variation in PaCO2 on myocardial blood flow (MBF), metabolism, and systemic hemodynamics in patients before elective coronary artery bypass graft surgery. In 10 male anesthetized patients, measurements of MBF, myocardial contractility, metabolism, and systemic hemodynamics were made in a randomized sequence at PaCO2 levels of 30, 40, and 50 mmHg, respectively. The MBF was measured using the Kety-Schmidt technique with argon as a tracer. End-diastolic left ventricular pressure and the maximal increase of left ventricular pressure were assessed using a manometer-tipped catheter. The cardiac index significantly changed with varying PaCO2 levels (hypocapnia, - 9%; hypercapnia, 13%). This reaction was associated with inverse changes in systemic vascular resistance index levels. The MBF significantly increased by 15% during hypercapnia, whereas no change was found during hypocapnia. Myocardial oxygen and glucose uptake and the maximal increase of left ventricular pressure were not affected by varying PaCO2 levels. In anesthetized patients with coronary artery disease, short-term variations in PaCO2 have significant effects on MBF but do not influence global myocardial oxygen and glucose uptake. Changes in systemic hemodynamics associated with respiratory alkalosis and acidosis are caused by changes in systemic vascular resistance rather than by alterations in myocardial contractility.

Genetics Home Reference: mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes

MedlinePlus

... my area? Other Names for This Condition MELAS MELAS syndrome mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like ... basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. Ann N Y Acad Sci. 2008 Oct;1142: ...

Genetics Home Reference: multiple mitochondrial dysfunctions syndrome

MedlinePlus

... babies have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can be life-threatening. They may ... or alpha-ketoglutarate dehydrogenase leads to potentially fatal lactic acidosis, encephalopathy, and other signs and symptoms of ...

Extracellular acidosis selectively inhibits pharmacomechanical coupling induced by carbachol in strips of rat gastric fundus.

PubMed

de Oliveira, Daniel Maia Nogueira; Batista-Lima, Francisco José; de Carvalho, Emanuella Feitosa; Havt, Alexandre; da Silva, Moisés Tolentino Bento; Dos Santos, Armênio Aguiar; Magalhães, Pedro Jorge Caldas

2017-12-01

What is the central question of this study? Acute acidosis that results from short-term exercise is involved in delayed gastric emptying in rats and the lower responsiveness of gastric fundus strips to carbachol. Does extracellular acidosis decrease responsiveness to carbachol in tissues of sedentary rats? How? What is the main finding and its importance? Extracellular acidosis inhibits cholinergic signalling in the rat gastric fundus by selectively influencing the G q/11 protein signalling pathway. Acute acidosis that results from short-term exercise delays gastric emptying in rats and decreases the responsiveness to carbachol in gastric fundus strips. The regulation of cytosolic Ca 2+ concentrations appears to be a mechanism of action of acidosis. The present study investigated the way in which acidosis interferes with gastric smooth muscle contractions. Rat gastric fundus isolated strips at pH 6.0 presented a lower magnitude of carbachol-induced contractions compared with preparations at pH 7.4. This lower magnitude was absent in carbachol-stimulated duodenum and KCl-stimulated gastric fundus strips. In Ca 2+ -free conditions, repeated contractions that were induced by carbachol progressively decreased, with no influence of extracellular pH. In fundus strips, CaCl 2 -induced contractions were lower at pH 6.0 than at pH 7.4 but only when stimulated in the combined presence of carbachol and verapamil. In contrast, verapamil-sensitive contractions that were induced by CaCl 2 in the presence of KCl did not change with pH acidification. In Ca 2+ store-depleted preparations that were treated with thapsigargin, the contractions that were induced by extracellular Ca 2+ restoration were smaller at pH 6.0 than at pH 7.4, but relaxation that was induced by SKF-96365 (an inhibitor of store-operated Ca 2+ entry) was unaltered by extracellular acidification. At pH 6.0, the phospholipase C inhibitor U-73122 relaxed carbachol-induced contractions less than at pH 7.4, and this phenomenon was absent in tissue that was treated with the RhoA kinase blocker Y-27632. Thus, extracellular acidosis inhibited pharmacomechanical coupling in gastric fundus by selectively inhibiting the G q/11 protein signalling pathway, whereas electromechanical coupling remained functionally preserved. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Effects of Different Oral Doses of Sodium Chloride on the Basal Acid-Base and Mineral Status of Exercising Horses Fed Low Amounts of Hay.

PubMed

Zeyner, Annette; Romanowski, Kristin; Vernunft, Andreas; Harris, Patricia; Müller, Ann-Marie; Wolf, Carola; Kienzle, Ellen

2017-01-01

The provision of NaCl, according to current recommendations, to horses in moderate work has been shown to induce immediate postprandial acidosis. The present study aimed to clarify whether this NaCl induced acidosis i) persists beyond the immediate postprandial period, and ii) is still present after a 2 week adaptation period. Six adult warmblood mares in moderate work received daily 1.00 kg hay per 100 kg body weight (bwt) only together with 0.64 kg unprocessed cereal grains/100 kg bwt.d as fed basis. Using a 3x3 Latin Square, either 0 (NaCl-0), 50 (NaCl-50) or 100 (NaCl-100) g NaCl/d were fed together with the concentrates in two equal doses for 3 weeks. During the final week, a mineral digestibility trial was undertaken. The middle sodium and chloride intake (NaCl-50) at least met the most common recommendations for moderate work. Morning (7:00 AM) urine and venous blood samples were collected on days 0, 1-4, 8, and 15, and analysed for pH, acid-base status, creatinine and electrolyte concentrations. Fractional electrolyte clearances (FC) were determined. Mean apparent sodium digestibility ranged between 60-62% whereas chloride digestibility was consistently above 94%. Supplementing 100 g but not 50 g of NaCl resulted in significant reduction of blood pH and base excess as well as urinary pH and urine acid excretion. Both 50 g and 100 g NaCl supplementation caused a significant reduction in base and net acid-base excretion, urine density and potassium concentration, but increased urine sodium concentration and the FC of sodium and chloride (P < 0.05). This suggests that a high proportion of the recommended salt doses is excreted renally. The above effects of NaCl supplementation persisted over the 2 week measurement period. Results suggest that feeding 100 g NaCl to moderately exercising horses results in mild metabolic acidosis, whereas feeding 50 g according to current recommendations resulted in compensated acidosis.

Effects of Different Oral Doses of Sodium Chloride on the Basal Acid-Base and Mineral Status of Exercising Horses Fed Low Amounts of Hay

PubMed Central

Zeyner, Annette; Romanowski, Kristin; Vernunft, Andreas; Harris, Patricia; Müller, Ann-Marie; Wolf, Carola; Kienzle, Ellen

2017-01-01

The provision of NaCl, according to current recommendations, to horses in moderate work has been shown to induce immediate postprandial acidosis. The present study aimed to clarify whether this NaCl induced acidosis i) persists beyond the immediate postprandial period, and ii) is still present after a 2 week adaptation period. Six adult warmblood mares in moderate work received daily 1.00 kg hay per 100 kg body weight (bwt) only together with 0.64 kg unprocessed cereal grains/100 kg bwt.d as fed basis. Using a 3x3 Latin Square, either 0 (NaCl-0), 50 (NaCl-50) or 100 (NaCl-100) g NaCl/d were fed together with the concentrates in two equal doses for 3 weeks. During the final week, a mineral digestibility trial was undertaken. The middle sodium and chloride intake (NaCl-50) at least met the most common recommendations for moderate work. Morning (7:00 AM) urine and venous blood samples were collected on days 0, 1–4, 8, and 15, and analysed for pH, acid-base status, creatinine and electrolyte concentrations. Fractional electrolyte clearances (FC) were determined. Mean apparent sodium digestibility ranged between 60–62% whereas chloride digestibility was consistently above 94%. Supplementing 100 g but not 50 g of NaCl resulted in significant reduction of blood pH and base excess as well as urinary pH and urine acid excretion. Both 50 g and 100 g NaCl supplementation caused a significant reduction in base and net acid-base excretion, urine density and potassium concentration, but increased urine sodium concentration and the FC of sodium and chloride (P < 0.05). This suggests that a high proportion of the recommended salt doses is excreted renally. The above effects of NaCl supplementation persisted over the 2 week measurement period. Results suggest that feeding 100 g NaCl to moderately exercising horses results in mild metabolic acidosis, whereas feeding 50 g according to current recommendations resulted in compensated acidosis. PMID:28045916

Health Effects of Alkaline Diet and Water, Reduction of Digestive-tract Bacterial Load, and Earthing.

PubMed

Mousa, Haider Abdul-Lateef

2016-04-01

In the article, the author discusses the issue of chronic, low-grade acidosis that is thought to be brought about primarily by 2 factors: (1) advancing age, with a consequent decline in renal function; and (2) diet. An acid-forming diet can induce low-grade metabolic acidosis, which causes very small decreases in blood pH and plasma bicarbonate (HCO3-) that remain within the range considered to be normal. However, if the duration of the acidosis is prolonged or chronically present, even a low degree of acidosis can become significant. This article reviews supporting evidence in the literature that has shown that consumption of abundant alkaline-forming foods can result in improvement in bone mineral density (BMD) and muscle mass, protection from chronic illnesses, reduced tumor-cell invasion and metastasis, and effective excretion of toxins from the body. In addition, a large number of studies showing the benefits of alkaline water (mineral water) have revealed that people consuming water with a high level of total dissolved solids (TDS) (ie, with a high mineral content) have shown a lower incidence of coronary heart disease (CHD), cardiovascular disease (CVD), and cancer and lower total mortality rates. Consumption of alkaline water also may prevent osteoporosis and protect pancreatic beta cells with its antioxidant effects. In addition, this article discusses the literature that shows that reducing digestive-tract bacterial load can play an important role in increasing blood alkalinity toward the normal upper limit. That change occurs through good oral hygiene, flossing of teeth, perfect chewing of food, and bowel evacuation as soon as possible. Finally, the author reviews the literature that shows that earthing (ie, the direct contact of the human body with the earth) can supply a current of plentiful electrons. Earthing has been shown to reduce acute and chronic inflammation, blood glucose in patients with diabetes, red blood cell (RBC) aggregation, and blood coagulation. It also has been shown to produce symptomatic improvement in chronic, muscle and joint pain, a reduction in overall stress levels and tensions, a boost in positive moods, an improvement in heart rate variability, and an improvement in the immune response.

Use of Elements of the Stewart Model (Strong Ion Approach) - SID3, SID4, Atot/A-, SIDe and SIG for the Diagnostics of Respiratory Acidosis in Brachycephalic Dogs.

PubMed

Sławuta, P; Sapikowski, G; Sobieraj, B

2016-09-01

Buffer systems of blood and tissues, which have the ability to bind with and give up hydrogen ions, participate in maintaining the acid-base balance (ABB) of the organism. According to the classic model, the system of carbonic acid and bicarbonates, where the first component serves the role of an acid and the second a base, determines plasma pH. The so-called Stewart model, which assumes that ions in blood serum can be separated into completely dissociated - nonbuffer and not dissociated - buffer ions which may give up or accept H+ions, also describes the ABB of the organism. The goal of the study was to find out whether, during respiratory acidosis, the values of SID3, SID4, Atot/A-, SIDe and SIG change. The study was carried out on 60 adult dogs of the boxer breed (32 males and 28 females) in which, on the basis of an arterial blood test, respiratory acidosis was found. A strong overgrowth of the soft palate tissue requiring a surgical correction was the cause of the ABB disorder. Prior to surgery and on the 14th day after the surgery, venous and arterial blood was drawn from each dog. ABB parameters were determined in the arterial blood sample: the blood pH, pCO2 and HCO3-. In the venous blood, concentration of Na+, K+, Cl-, lactate-, albumins, and Pinorganic was determined. On the basis of the obtained data, the values of SID3, SID4, SIDe, A- and SIG, before and after the surgery, were calculated. In spite of the fact that the average concentration of ions, albumins, Pinorganic and lactate in the blood serum of dogs before and after the surgical procedure was similar and within the physiological norms, the values of SID3, SIDe and SIG, calculated on the basis of the former, displayed statistically significant differences. On the basis of the results obtained, it can be stated that the values of SID3, SIDe and SIG change during respiratory acidosis and may be helpful in the diagnostics of ABB disorders in brachycephalic dogs.

Fatigue during high-intensity intermittent exercise: application to bodybuilding.

PubMed

Lambert, Charles P; Flynn, Michael G

2002-01-01

Resistance exercise is an activity performed by individuals interested in competition, those who wish to improve muscle mass and strength for other sports, and for individuals interested in improving their strength and physical appearance. In this review we present information suggesting that phosphocreatine depletion, intramuscular acidosis and carbohydrate depletion are all potential causes of the fatigue during resistance exercise. In addition, recommendations are provided for nutritional interventions, which might delay muscle fatigue during this type of activity.

Ecology and pathogenicity of gastrointestinal Streptococcus bovis.

PubMed

Herrera, Paul; Kwon, Young Min; Ricke, Steven C

2009-01-01

Streptococcus bovis is an indigenous resident in the gastrointestinal tracts of both humans and animals. S. bovis is one of the major causes of bacterial endocarditis and has been implicated in the incidence of human colon cancer, possibly due to chronic inflammatory response at the site of intestinal colonization. Certain feeding regimens in ruminants can lead to overgrowth of S. bovis in the rumen, resulting in the over-production of lactate and capsular polysaccharide causing acute ruminal acidosis and bloat, respectively. There are multiple strategies in controlling acute lactic acidosis and bloat. The incidence of the two diseases may be controlled by strict dietary management. Gradual introduction of grain-based diets and the feeding of coarsely chopped roughage decrease the incidence of the two disease entities. Ionophores, which have been used to enhance feed conversion and growth rate in cattle, have been shown to inhibit the growth of lactic acid bacteria in the rumen. Other methods of controlling lactic acid bacteria in the ruminal environment (dietary supplementation of long-chain fatty acids, induction of passive and active immune responses to the bacteria, and the use of lytic bacteriophages) have also been investigated. It is anticipated that through continued in-depth ecological analysis of S. bovis the characteristics responsible for human and animal pathogenesis would be sufficiently identified to a point where more effective control strategies for the control of this bacteria can be developed.

[Current role of metformin in treatment of diabetes mellitus type 2].

PubMed

Janssen, J A

2000-09-30

Metformin-associated lactic acidosis is not necessarily due to metformin accumulation. It appears that mortality in patients receiving metformin who develop lactic acidosis is mostly linked to underlying disease. It has been suggested that metformin should be the first-line agent for the treatment of obese type 2 diabetic patients since metformin was associated with a significant decrease in macrovascular events and a reduction of all-cause mortality in the United Kingdom Prospective Diabetes Study (UKPDS) in a substudy. However, in this substudy no significant decrease in microvascular complications was observed in obese subjects with intensive metformin therapy. In addition, the use of metformin in combination with sulfonylurea seemed to be associated with excess risk of diabetes-related and all-cause mortality in obese subjects. Due to the discrepant and contradictory nature of the results in the obese patients and a lack of power the UKPDS offered no decision for any drug for initial therapy of type 2 diabetes. The main message of the UKPDS is that lowering of the blood glucose to the normal range is beneficial irrespective of the hypoglycaemic agent used. A rational approach to therapy in a type 2 diabetes patient who fails to sufficiently lower blood sugar with diet and weight loss is to begin therapy with a sulfonylurea or metformin and to add another oral agent if the desired glycaemic control is not achieved.

Lactic acidosis and hyperamylasaemia associated with phenformin therapy

PubMed Central

Williams, D. N.; Knight, A. H.; Goldberg, D. M.

1974-01-01

A case is described of lactic acidosis and hyperamylasaemia in a diabetic with impaired renal function treated with phenformin. Despite normal blood pressure and adequate tissue perfusion, the patient succumbed. No evidence of pancreatitis could be found at autopsy. PMID:4219857

Phaeochromocytoma presenting with pseudo-intestinal obstruction and lactic acidosis.

PubMed

Kek, Peng Chin; Ho, Emily Tse Lin; Loh, Lih Ming

2015-08-01

Phaeochromocytomas are rare neuroendocrine tumours with variable clinical signs and symptoms. Hypertension, tachycardia, sweating and headaches are cardinal manifestations. Although nausea and abdominal pain are the more common gastrointestinal features, rare gastrointestinal spectrums have been reported that can mimic abdominal emergencies. Metabolic effects of hypercatecholaminaemia are vast and one such rare presentation is lactic acidosis. We describe a case of phaeochromocytoma presenting with both intestinal pseudo-obstruction as well as lactic acidosis. This case report highlights the importance of having a high index of suspicion for and early recognition of the gastrointestinal and metabolic manifestations of phaeochromocytomas.

[High anion gap metabolic acidosis (pyroglutamic acidosis) induced by chronic acetaminophen use].

PubMed

Tchougang Nono, J; Mistretta, V; Noirot, I; Canivet, J L; Damas, P

2018-01-01

Acetaminophen is the most consumable analgesic in the world in the form of medical prescription or self-medication. It is one of the active ingredients most often involved in voluntary poisoning. Lethal dose of acetaminophen classically induces acute hepatic failure on hepatic necrosis. Chronic intake of sub-lethal doses (i.e. near recommended therapeutic doses) of acetaminophen in the presence of certain risk factors may be responsible for another much less recognized pathological manifestation: severe metabolic acidosis with an increased anion gap due to the accumulation of 5-oxoproline or pyroglutamic acid.

Paralysis Episodes in Carbonic Anhydrase II Deficiency.

PubMed

Al-Ibrahim, Alia; Al-Harbi, Mosa; Al-Musallam, Sulaiman

2003-01-01

Carbonic anhydrase II (CAII) deficiency is an autosomal recessive disorder manifest by osteopetrosis, renal tubular acidosis, and cerebral calcification. Other features include growth failure and mental retardation. Complications of the osteopetrosis include frequent bone fractures, cranial nerve compression, and dental mal-occlusion. A hyper-chloremic metabolic acidosis, sometimes with hypokalemia, occurs due to renal tubular acidosis that may be proximal, distal, or more commonly, the combined type. Such patients may present with global hypotonia, muscle weakness or paralysis. We report a case of CA II deficiency with recurrent attacks of acute paralysis which was misdiagnosed initially as Guillian-Barre syndrome.

Con: Higher serum bicarbonate in dialysis patients is protective.

PubMed

Chauveau, Philippe; Rigothier, Claire; Combe, Christian

2016-08-01

Metabolic acidosis is often observed in advanced chronic kidney disease, with deleterious consequences on the nutritional status, bone and mineral status, inflammation and mortality. Through clearance of the daily acid load and a net gain in alkaline buffers, dialysis therapy is aimed at correcting metabolic acidosis. A normal bicarbonate serum concentration is the recommended target in dialysis patients. However, several studies have shown that a mild degree of metabolic acidosis in patients treated with dialysis is associated with better nutritional status, higher protein intake and improved survival. Conversely, a high bicarbonate serum concentration is associated with poor nutritional status and lower survival. It is likely that mild acidosis results from a dietary acid load linked to animal protein intake. In contrast, a high bicarbonate concentration in patients treated with dialysis could result mainly from an insufficient dietary acid load, i.e. low protein intake. Therefore, a high pre-dialysis serum bicarbonate concentration should prompt nephrologists to carry out nutritional investigations to detect insufficient dietary protein intake. In any case, a high bicarbonate concentration should be neither a goal of dialysis therapy nor an index of adequate dialysis, whereas mild acidosis could be considered as an indicator of appropriate protein intake. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Sjögren syndrome presenting with hypopotassemic periodic paralysis due to renal tubular acidosis

PubMed Central

Ataoglu, Esra Hayriye; Demir, Betul; Tuna, Mazhar; Çavus, Bilger; Cetin, Faik; Temiz, Levent Umit; Ozturk, Savas; Yenigun, Mustafa

2012-01-01

Summary Background: Sjögren syndrome (SS) is an autoimmune-lymphoproliferative disorder characterized by mononuclear cell infiltration of exocrine glands. Clinically, Sjögren syndrome (SS) has a wide spectrum, varying from autoimmune exocrinopathy to systemic involvement. There have been few cases reporting that primary SS developed with distal renal tubular acidosis clinically. Case Report: Here, we present a case with primary Sjögren syndrome accompanied by hypopotassemic paralysis due to renal tubular acidosis. Severe hypopotassemia, hyperchloremic metabolic acidosis, alkaline urine and disorder in urinary acidification test were observed in the biochemical examination of the 16-year-old female patient, who had applied to our clinic for extreme loss of muscle force. After the examinations it was determined that the patient had developed Type 1 RTA (distal RTA) due to primary Sjögren syndrome. Potassium and alkaline replacement was made and an immediate total recovery was achieved. Conclusions: Hypopotassemic paralysis due to primary Sjögren syndrome is a rare but severe disorder that could lead to death if not detected early and cured appropriately. Thus, effective treatment should be immediately initiated in cases where severe hypopotassemia is accompanied by metabolic acidosis, and the cases should also be examined for extraglandular involvement of SS. PMID:23569525

Changes in Whole-Body Oxygen Consumption and Skeletal Muscle Mitochondria During Linezolid-Induced Lactic Acidosis.

PubMed

Protti, Alessandro; Ronchi, Dario; Bassi, Gabriele; Fortunato, Francesco; Bordoni, Andreina; Rizzuti, Tommaso; Fumagalli, Roberto

2016-07-01

To better clarify the pathogenesis of linezolid-induced lactic acidosis. Case report. ICU. A 64-year-old man who died with linezolid-induced lactic acidosis. Skeletal muscle was sampled at autopsy to study mitochondrial function. Lactic acidosis developed during continuous infusion of linezolid while oxygen consumption and oxygen extraction were diminishing from 172 to 52 mL/min/m and from 0.27 to 0.10, respectively. Activities of skeletal muscle respiratory chain complexes I, III, and IV, encoded by nuclear and mitochondrial DNA, were abnormally low, whereas activity of complex II, entirely encoded by nuclear DNA, was not. Protein studies confirmed stoichiometric imbalance between mitochondrial (cytochrome c oxidase subunits 1 and 2) and nuclear (succinate dehydrogenase A) DNA-encoded respiratory chain subunits. These findings were not explained by defects in mitochondrial DNA or transcription. There were no compensatory mitochondrial biogenesis (no induction of nuclear respiratory factor 1 and mitochondrial transcript factor A) or adaptive unfolded protein response (reduced concentration of heat shock proteins 60 and 70). Linezolid-induced lactic acidosis is associated with diminished global oxygen consumption and extraction. These changes reflect selective inhibition of mitochondrial protein synthesis (probably translation) with secondary mitonuclear imbalance. One novel aspect of linezolid toxicity that needs to be confirmed is blunting of reactive mitochondrial biogenesis and unfolded protein response.

Comparison of potential risks of lactic acidosis induction by biguanides in rats.

PubMed

Bando, Kiyoko; Ochiai, Shoko; Kunimatsu, Takeshi; Deguchi, Jiro; Kimura, Juki; Funabashi, Hitoshi; Seki, Takaki

2010-10-01

Lactic acidosis has been considered to be a side effect of some biguanides, after phenformin was withdrawn from the market because of its association with lactic acidosis. The potential of lactic acidosis induced by biguanides at human therapeutic exposure levels, however, has not been examined. Then, we compared the risk of lactic acid at doses providing exposure levels comparable to human therapeutic doses. Metformin and phenformin were orally administered to rats for up to 28 days, and plasma drug concentrations and blood lactic acid levels were examined. Metformin did not elevate lactic acid levels at the dose corresponding to higher systemic drug exposure than human therapeutic level, even for repeated doses. In contrast, phenformin elevated lactic acid levels at the dose corresponding to lower exposure than human therapeutic level, and sustained high levels were observed up to 24h post-dose; furthermore, these changes were enhanced by repeated doses. Direct comparison at each rat equivalent dose clearly indicated that lactic acid levels of phenformin were higher than those of metformin. These non-clinical findings suggest that metformin dose not increase lactic acid levels like phenformin does, and therefore may not increase the risk for lactic acidosis at human therapeutic exposure level. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Structural alterations by five disease-causing mutations in the low-pH conformation of human dihydrolipoamide dehydrogenase (hLADH) analyzed by molecular dynamics - Implications in functional loss and modulation of reactive oxygen species generation by pathogenic hLADH forms.

PubMed

Ambrus, Attila; Mizsei, Reka; Adam-Vizi, Vera

2015-07-01

Human dihydrolipoamide dehydrogenase (hLADH) is a flavoenzyme component (E3) of the human alpha-ketoglutarate dehydrogenase complex (α-KGDHc) and few other dehydrogenase complexes. Pathogenic mutations of hLADH cause severe metabolic diseases (atypical forms of E3 deficiency) that often escalate to cardiological or neurological presentations and even premature death; the pathologies are generally accompanied by lactic acidosis. hLADH presents a distinct conformation under acidosis (pH 5.5-6.8) with lower physiological activity and the capacity of generating reactive oxygen species (ROS). It has been shown by our laboratory that selected pathogenic mutations, besides lowering the physiological activity of hLADH, significantly stimulate ROS generation by hLADH, especially at lower pH, which might play a role in the pathogenesis of E3-deficiency in respective cases. Previously, we generated by molecular dynamics (MD) simulation the low-pH hLADH structure and analyzed the structural changes induced in this structure by eight of the pathogenic mutations of hLADH. In the absence of high resolution mutant structures these pieces of information are crucial for the mechanistic investigation of the molecular pathogeneses of the hLADH protein. In the present work we analyzed by molecular dynamics simulation the structural changes induced in the low-pH conformation of hLADH by five pathogenic mutations of hLADH; the structures of these disease-causing mutants of hLADH have never been examined before.

A patient with cystinosis presenting like bartter syndrome and review of literature.

PubMed

Ertan, Pelin; Evrengul, Havva; Ozen, Serkan; Emre, Sinan

2012-12-01

Nephropathic cystinosis is an autosomal recessively inherited metabolic disorder presenting with metabolic acidosis, Fanconi syndrome and renal failure. We present a 6-year-old girl with severe growth failure, hyponatremia and hypokalemia. Her parents were 4(th) degree relatives. Two relatives were diagnosed as end stage renal failure. She also had persistant hypokalemic hypochloremic metabolic alkalosis. Her renal function was normal at presentation. She was thought to have Bartter syndrome with supporting findings of elevated levels of renin and aldosterone with normal blood pressure, and hyperplasia of juxtaglomerular apparatus. Her metabolic alkalosis did not resolve despite supportive treatment. At 6(th) month of follow-up proteinuria, glucosuria and deterioration of renal function developed. Diagnosis of cystinosis was made with slit lamp examination and leukocyte cystine levels. At 12(th) month of follow-up her metabolic alkalosis has converted to metabolic acidosis. In children presenting with persistant metabolic alkalosis, with family history of renal failure, and parental consanguinity, cystinosis should always be kept in mind as this disease is an important cause of end stage renal failure which may have features mimmicking Bartter syndrome.

Hypercapnia and low pH induce neuroepithelial cell proliferation and emersion behaviour in the amphibious fish Kryptolebias marmoratus.

PubMed

Robertson, Cayleih E; Turko, Andy J; Jonz, Michael G; Wright, Patricia A

2015-10-01

Aquatic hypercapnia may have helped to drive ancestral vertebrate invasion of land. We tested the hypothesis that amphibious fishes sense and respond to elevated aquatic PCO2 by behavioural avoidance mechanisms, and by morphological changes at the chemoreceptor level. Mangrove rivulus (Kryptolebias marmoratus) were exposed to 1 week of normocapnic control water (pH 8), air, hypercapnia (5% CO2, pH 6.8) or isocapnic acidosis (pH 6.8). We found that the density of CO2/H(+) chemoreceptive neuroepithelial cells (NECs) was increased in hypercapnia or isocapnic acidosis-exposed fish. Projection area (a measure of cell size) was unchanged. Acute exposure to progressive hypercapnia induced the fish to emerse (leave water) at water pH values ∼6.1, whereas addition of HCl to water caused a more variable response with a lower pH threshold (∼pH 5.5). These results support our hypothesis and suggest that aquatic hypercapnia provides an adequate stimulus for extant amphibious fishes to temporarily transition from aquatic to terrestrial habitats. © 2015. Published by The Company of Biologists Ltd.

The patient with a severe degree of metabolic acidosis: a deductive analysis.

PubMed

Maccari, C; Kamel, K S; Davids, M R; Halperin, M L

2006-07-01

This teaching exercise demonstrates how principles of physiology might help in identifying the cause of a particularly severe case of metabolic acidosis and making appropriate decisions about therapy. The patient's plasma pH was 7.00 and their plasma bicarbonate concentration was 2 mmol/l. Because the time course of the patient's illness was believed to be <24 h, this suggested that a large quantity of acid had been added to the body in this short time period, but the medical team managing the case could not identify any acid that could have been produced rapidly by endogenous processes, or was ingested by the patient. Moreover, there was a question about how such a very low arterial PCO(2) (8 mmHg) could be sustained. Even once the diagnosis was made, there were issues to resolve concerning therapy. These included questions about how much sodium bicarbonate to administer, and what dangers might arise during this therapy. The missing links in this interesting story emerge during a discussion between the medical team and their imaginary mentor, Professor McCance.

[Case of young woman with Graves' disease and incomplete distal renal tubular acidosis with severe progress and cardiac arrest].

PubMed

Klimm, Wojciech; Kade, Grzegorz; Spaleniak, Sebastian; Dubchak, Ivanna; Niemczyk, Stanisław

2014-07-01

Diagnostic of renal tubular disorders can be often difficult. Incomplete form of distal Renal Tubular Acidosis (dRta) in course of Graves' disease was de novo recognized in a young woman hospitalized with a deep deficiency of potassium in blood serum complicated with cardiac arrest. Series of tests assessing the types and severity of water-electrolyte, acid-base and thyroid disorders were performed during a complex diagnosis. During the treatment of acute phase of the disease we intensified efforts to maintain basic life functions and to eliminate deep water-electrolyte disturbances. In the second phase of the treatment we determined an underlying cause of the disease, recognized dRTA, and introduced a specific long-term electrolyte and hormonal therapy. To confirm the diagnosis oral test with ammonium chloride (Wrong-Davies' test) was performed. After completion of the diagnostic and therapeutic process, the patient was included in the nephrological supervision on an outpatient basis. The basic drug for the therapy was sodium citrate. After a year of observation and continuing treatment we evaluated therapeutic results as good and permanent.

The medaka mutation tintachina sheds light on the evolution of V-ATPase B subunits in vertebrates

NASA Astrophysics Data System (ADS)

Müller, Claudia; Maeso, Ignacio; Wittbrodt, Joachim; Martínez-Morales, Juan R.

2013-11-01

Vacuolar-type H+ ATPases (V-ATPases) are multimeric protein complexes that play a universal role in the acidification of intracellular compartments in eukaryotic cells. We have isolated the recessive medaka mutation tintachina (tch), which carries an inactivating modification of the conserved glycine residue (G75R) of the proton pump subunit atp6v1Ba/vatB1. Mutant embryos show penetrant pigmentation defects, massive brain apoptosis and lethality before hatching. Strikingly, an equivalent mutation in atp6v1B1 (G78R) has been reported in a family of patients suffering from distal renal tubular acidosis (dRTA), a hereditary disease that causes metabolic acidosis due to impaired kidney function. This poses the question as to how molecularly identical mutations result in markedly different phenotypes in two vertebrate species. Our work offers an explanation for this phenomenon. We propose that, after successive rounds of whole-genome duplication, the emergence of paralogous copies allowed the divergence of the atp6v1B cis-regulatory control in different vertebrate groups.

Sperm from sneaker male squids exhibit chemotactic swarming to CO₂.

PubMed

Hirohashi, Noritaka; Alvarez, Luis; Shiba, Kogiku; Fujiwara, Eiji; Iwata, Yoko; Mohri, Tatsuma; Inaba, Kazuo; Chiba, Kazuyoshi; Ochi, Hiroe; Supuran, Claudiu T; Kotzur, Nico; Kakiuchi, Yasutaka; Kaupp, U Benjamin; Baba, Shoji A

2013-05-06

Behavioral traits of sperm are adapted to the reproductive strategy that each species employs. In polyandrous species, spermatozoa often form motile clusters, which might be advantageous for competing with sperm from other males. Despite this presumed advantage for reproductive success, little is known about how sperm form such functional assemblies. Previously, we reported that males of the coastal squid Loligo bleekeri produce two morphologically different euspermatozoa that are linked to distinctly different mating behaviors. Consort and sneaker males use two distinct insemination sites, one inside and one outside the female's body, respectively. Here, we show that sperm release a self-attracting molecule that causes only sneaker sperm to swarm. We identified CO2 as the sperm chemoattractant and membrane-bound flagellar carbonic anhydrase as its sensor. Downstream signaling results from the generation of extracellular H(+), intracellular acidosis, and recovery from acidosis. These signaling events elicit Ca(2+)-dependent turning behavior, resulting in chemotactic swarming. These results illuminate the bifurcating evolution of sperm underlying the distinct fertilization strategies of this species. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sodium bicarbonate on severe metabolic acidosis during prolonged cardiopulmonary resuscitation: a double-blind, randomized, placebo-controlled pilot study.

PubMed

Ahn, Shin; Kim, Youn-Jung; Sohn, Chang Hwan; Seo, Dong Woo; Lim, Kyoung Soo; Donnino, Michael W; Kim, Won Young

2018-04-01

Sodium bicarbonate administration during cardiopulmonary resuscitation (CPR) is controversial. Current guidelines recommend sodium bicarbonate injection in patients with existing metabolic acidosis, but clinical trials, particularly, those involving patients with acidosis, are limited. We aimed to evaluate the efficacy of sodium bicarbonate administration in out-of-hospital cardiac arrest (OHCA) patients with severe metabolic acidosis during prolonged CPR. Prospective, double-blind, randomized placebo-controlled pilot trial was conducted between January 2015 and December 2015, at a single center emergency department (ED). After 10 minutes of CPR, patients who failed to achieve return of spontaneous circulation (ROSC) and with severe metabolic acidosis (pH<7.1 or bicarbonate <10 mEq/L) were enrolled. Sodium bicarbonate (n=25) or normal saline (n=25) were administered. The primary end point was sustained ROSC. The secondary end points were the change of acidosis and good neurologic survival. Sodium bicarbonate group had significant effect on pH (6.99 vs. 6.90, P=0.038) and bicarbonate levels (21.0 vs. 8.0 mEq/L, P=0.007). However, no significant differences showed between sodium bicarbonate and placebo groups in sustained ROSC (4.0% vs. 16.0%, P=0.349) or good neurologic survival at 1 month (0.0% vs. 4.0%, P=1.000). The use of sodium bicarbonate improved acid-base status, but did not improve the rate of ROSC and good neurologic survival. We could not draw a conclusion, but our pilot data could be used to design a larger trial to verify the efficacy of sodium bicarbonate. NCT02303548 (http://www.ClinicalTrials.gov).

Acidosis downregulates platelet haemostatic functions and promotes neutrophil proinflammatory responses mediated by platelets.

PubMed

Etulain, Julia; Negrotto, Soledad; Carestia, Agostina; Pozner, Roberto Gabriel; Romaniuk, María Albertina; D'Atri, Lina Paola; Klement, Giannoula Lakka; Schattner, Mirta

2012-01-01

Acidosis is one of the hallmarks of tissue injury such as trauma, infection, inflammation, and tumour growth. Although platelets participate in the pathophysiology of all these processes, the impact of acidosis on platelet biology has not been studied outside of the quality control of laboratory aggregation assays or platelet transfusion optimization. Herein, we evaluate the effect of physiologically relevant changes in extracellular acidosis on the biological function of platelets, placing particular emphasis on haemostatic and secretory functions. Platelet haemostatic responses such as adhesion, spreading, activation of αIIbβ3 integrin, ATP release, aggregation, thromboxane B2 generation, clot retraction and procoagulant activity including phosphatidilserine exposure and microparticle formation, showed a statistically significant inhibition of thrombin-induced changes at pH of 7.0 and 6.5 compared to the physiological pH (7.4). The release of alpha granule content was differentially regulated by acidosis. At low pH, thrombin or collagen-induced secretion of vascular endothelial growth factor and endostatin were dramatically reduced. The release of von Willebrand factor and stromal derived factor-1α followed a similar, albeit less dramatic pattern. In contrast, the induction of CD40L was not changed by low pH, and P-selectin exposure was significantly increased. While the generation of mixed platelet-leukocyte aggregates and the increased chemotaxis of neutrophils mediated by platelets were further augmented under acidic conditions in a P-selectin dependent manner, the increased neutrophil survival was independent of P-selectin expression. In conclusion, our results indicate that extracellular acidosis downregulates most of the haemostatic platelet functions, and promotes those involved in amplifying the neutrophil-mediated inflammatory response.

Fetal distress and the condition of newborn infants.

PubMed Central

Sykes, G S; Molloy, P M; Johnson, P; Stirrat, G M; Turnbull, A C

1983-01-01

In a prospective audit of the obstetric management of 1210 consecutive deliveries the association was investigated between the need for operative delivery for fetal distress during labour and the condition of the newborn infant. Operative delivery was performed for only 11.5% of the newborn infants with severe acidosis at birth (umbilical artery pH less than 7.12, base deficit greater than 12 mmol (mEq)/1), 24.1% of those with an Apgar score less than 7 at one minute, and 15.8% of those with both severe acidosis and a one minute Apgar score less than 7. Most of the infants delivered operatively were in a vigorous condition at birth and did not have severe acidosis. Fetal blood sampling was done in 4.0% of labours. As none of the fetal blood values were less than 7.20 and only three of the infants sampled in utero suffered severe acidosis at birth, fetal blood sampling would have had to be performed much more often to provide a useful guide to metabolic state at birth. While the large majority of "at risk" fetuses had continuous fetal heart rate monitoring in labour, this had not been provided in 48.7% of the labours of infants with severe acidosis, 38.7% of infants with a one minute Apgar score less than 7, and 47.4% of infants with both severe acidosis and a one minute Apgar score less than 7. Continuous fetal heart rate monitoring was associated with a much higher incidence of operative delivery for fetal distress than was intermittent fetal heart rate auscultation. These results suggest an urgent need to review present methods for assessing the intrapartum condition of the fetus, making the diagnosis of fetal distress, and assessing the condition of the infant at birth. PMID:6412897

Acidosis-mediated regulation of the NHE1 isoform of the Na⁺/H⁺ exchanger in renal cells.

PubMed

Odunewu, Ayodeji; Fliegel, Larry

2013-08-01

The mammalian Na⁺/H⁺ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that regulates intracellular pH by removing a proton in exchange for extracellular sodium. Renal tissues are subject to metabolic and respiratory acidosis, and acidosis has been shown to acutely activate NHE1 activity in other cell types. We examined if NHE1 is activated by acute acidosis in HEK293 and Madin-Darby canine kidney (MDCK) cells. Acute sustained intracellular acidosis (SIA) activated NHE1 in both cell types. We expressed wild-type and mutant NHE1 cDNAs in MDCK cells. All the cDNAs had a L163F/G174S mutation, which conferred a 100-fold resistance to EMD87580, an NHE1-specific inhibitor. We assayed exogenous NHE1 activity while inhibiting endogenous activity with EMD87580 and while inhibiting the NHE3 isoform of the Na⁺/H⁺ exchanger using the isoform-specific inhibitor S3226. We examined the activation and phosphorylation of the wild-type and mutant NHE1 proteins in response to SIA. In MDCK cells we demonstrated that the amino acids Ser⁷⁷¹, Ser⁷⁷⁶, Thr⁷⁷⁹, and Ser⁷⁸⁵ are important for NHE1 phosphorylation and activation after acute SIA. SIA activated ERK-dependent pathways in MDCK cells, and this was blocked by treatment with the MEK inhibitor U0126. Treatment with U0126 also blocked activation of NHE1 by SIA. These results suggest that acute acidosis activates NHE1 in mammalian kidney cells and that in MDCK cells this activation occurs through an ERK-dependent pathway affecting phosphorylation of a distinct set of amino acids in the cytosolic regulatory tail of NHE1.

Regional acidosis locally inhibits but remotely stimulates Ca2+ waves in ventricular myocytes

PubMed Central

Ford, Kerrie L.; Moorhouse, Emma L.; Bortolozzi, Mario; Richards, Mark A.; Swietach, Pawel; Vaughan-Jones, Richard D.

2017-01-01

Abstract Aims Spontaneous Ca2+ waves in cardiomyocytes are potentially arrhythmogenic. A powerful controller of Ca2+ waves is the cytoplasmic H+ concentration ([H+]i), which fluctuates spatially and temporally in conditions such as myocardial ischaemia/reperfusion. H+-control of Ca2+ waves is poorly understood. We have therefore investigated how [H+]i co-ordinates their initiation and frequency. Methods and results Spontaneous Ca2+ waves were imaged (fluo-3) in rat isolated ventricular myocytes, subjected to modest Ca2+-overload. Whole-cell intracellular acidosis (induced by acetate-superfusion) stimulated wave frequency. Pharmacologically blocking sarcolemmal Na+/H+ exchange (NHE1) prevented this stimulation, unveiling inhibition by H+. Acidosis also increased Ca2+ wave velocity. Restricting acidosis to one end of a myocyte, using a microfluidic device, inhibited Ca2+ waves in the acidic zone (consistent with ryanodine receptor inhibition), but stimulated wave emergence elsewhere in the cell. This remote stimulation was absent when NHE1 was selectively inhibited in the acidic zone. Remote stimulation depended on a locally evoked, NHE1-driven rise of [Na+]i that spread rapidly downstream. Conclusion Acidosis influences Ca2+ waves via inhibitory Hi+ and stimulatory Nai+ signals (the latter facilitating intracellular Ca2+-loading through modulation of sarcolemmal Na+/Ca2+ exchange activity). During spatial [H+]i-heterogeneity, Hi+-inhibition dominates in acidic regions, while rapid Nai+ diffusion stimulates waves in downstream, non-acidic regions. Local acidosis thus simultaneously inhibits and stimulates arrhythmogenic Ca2+-signalling in the same myocyte. If the principle of remote H+-stimulation of Ca2+ waves also applies in multicellular myocardium, it raises the possibility of electrical disturbances being driven remotely by adjacent ischaemic areas, which are known to be intensely acidic. PMID:28339694

Regional acidosis locally inhibits but remotely stimulates Ca2+ waves in ventricular myocytes.

PubMed

Ford, Kerrie L; Moorhouse, Emma L; Bortolozzi, Mario; Richards, Mark A; Swietach, Pawel; Vaughan-Jones, Richard D

2017-07-01

Spontaneous Ca2+ waves in cardiomyocytes are potentially arrhythmogenic. A powerful controller of Ca2+ waves is the cytoplasmic H+ concentration ([H+]i), which fluctuates spatially and temporally in conditions such as myocardial ischaemia/reperfusion. H+-control of Ca2+ waves is poorly understood. We have therefore investigated how [H+]i co-ordinates their initiation and frequency. Spontaneous Ca2+ waves were imaged (fluo-3) in rat isolated ventricular myocytes, subjected to modest Ca2+-overload. Whole-cell intracellular acidosis (induced by acetate-superfusion) stimulated wave frequency. Pharmacologically blocking sarcolemmal Na+/H+ exchange (NHE1) prevented this stimulation, unveiling inhibition by H+. Acidosis also increased Ca2+ wave velocity. Restricting acidosis to one end of a myocyte, using a microfluidic device, inhibited Ca2+ waves in the acidic zone (consistent with ryanodine receptor inhibition), but stimulated wave emergence elsewhere in the cell. This remote stimulation was absent when NHE1 was selectively inhibited in the acidic zone. Remote stimulation depended on a locally evoked, NHE1-driven rise of [Na+]i that spread rapidly downstream. Acidosis influences Ca2+ waves via inhibitory Hi+ and stimulatory Nai+ signals (the latter facilitating intracellular Ca2+-loading through modulation of sarcolemmal Na+/Ca2+ exchange activity). During spatial [H+]i-heterogeneity, Hi+-inhibition dominates in acidic regions, while rapid Nai+ diffusion stimulates waves in downstream, non-acidic regions. Local acidosis thus simultaneously inhibits and stimulates arrhythmogenic Ca2+-signalling in the same myocyte. If the principle of remote H+-stimulation of Ca2+ waves also applies in multicellular myocardium, it raises the possibility of electrical disturbances being driven remotely by adjacent ischaemic areas, which are known to be intensely acidic. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.

A Stand-Alone Synbiotic Treatment for the Prevention of D-Lactic Acidosis in Short Bowel Syndrome

PubMed Central

Takahashi, Kazuhiro; Terashima, Hideo; Kohno, Keisuke; Ohkohchi, Nobuhiro

2013-01-01

Synbiotics are combinations of probiotics and prebiotics that have recently been used in the context of various gastrointestinal diseases, including infectious enteritis, inflammatory bowel disease, and bowel obstruction. We encountered a patient with recurrent D-lactic acidosis who was treated successfully for long periods using synbiotics. The patient was diagnosed as having short bowel syndrome and had recurrent episodes of neurologic dysfunction due to D-lactic acidosis. In addition to fasting, the patient had been treated with antibiotics to eliminate D-lactate–producing bacteria. After the failure of antibiotic treatment, a stand-alone synbiotic treatment was started, specifically Bifidobacterium breve Yakult and Lactobacillus casei Shirota as probiotics, and galacto-oligosaccharide as a prebiotic. Serum D-lactate levels declined, and the patient has been recurrence-free for 3 years without dietary restriction. Synbiotics allowed the reduction in colonic absorption of D-lactate by both prevention of D-lactate–producing bacterial overgrowth and stimulation of intestinal motility, leading to remission of D-lactate acidosis. PMID:23701144

Lentiform fork sign: a magnetic resonance finding in a case of acute metabolic acidosis.

PubMed

Grasso, Daniela; Borreggine, Carmela; Perfetto, Francesco; Bertozzi, Vincenzo; Trivisano, Marina; Specchio, Luigi Maria; Grilli, Gianpaolo; Macarini, Luca

2014-06-01

We report a 33 year-old woman addicted to chronic unspecified solvents abuse with stupor, respiratory disorders, tetraplegia and severe metabolic acidosis. On admission an unenhanced cranial CT scan showed symmetrical hypodensities of both lentiform nuclei. MR imaging performed 12 hours after stupor demonstrates bilateral putaminal hemorrhagic necrosis, bilateral external capsule, corona radiata and deep cerebellar hyperintensities with right cingulate cortex involvement. DWI reflected bilateral putaminal hyperintensities with restricted water diffusion as to citotoxic edema and development of vasogenic edema in the external capsule recalling a fork. On day twenty, after specific treatments MRI demonstrated a bilateral putaminal marginal enhancement. Bilateral putaminal necrosis is a characteristic but non-specific radiological finding of methanol poisoning. Lentiform Fork sign is a rare MRI finding reported in literature in 22 patients with various conditions characterized by metabolic acidosis. Vasogenic edema may be due to the differences in metabolic vulnerability between neurons and astrocytes. We postulate that metabolic acidosis could have an important role to generate this sign.

Neonatal metabolic acidosis at birth: In search of a reliable marker.

PubMed

Racinet, C; Ouellet, P; Charles, F; Daboval, T

2016-06-01

A newborn may present acidemia on the umbilical artery blood which can result from respiratory acidosis or metabolic acidosis or be of mixed origin. Currently, in the absence of a satisfactory definition, the challenge is to determine the most accurate marker for metabolic acidosis, which can be deleterious for the neonate. We reviewed the methodological and physiological aspects of the perinatal literature to search for the best marker of NMA. Base deficit and pH have been criticized as the standard criteria to predict outcome. The proposed threshold of pathogenicity is not based on convincing studies. The algorithms of various blood gas analyzers differ and do not take into account the specific neonatal acid-base profile. Birth-related neonatal eucapnic pH is described as the most pertinent marker of NMA at birth. The various means of calculating this value and the level below which it seems to play a possible pathogenic role are presented. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Effect of induced ruminal acidosis on blood variables in heifers

PubMed Central

2013-01-01

Background Ruminal acidosis is responsible for the onset of different pathologies in dairy and feedlot cattle, but there are major difficulties in the diagnosis. This study modelled the data obtained from various blood variables to identify those that could indicate the severity of ruminal acidosis. Six heifers were fed three experimental rations throughout three periods. The diets were characterised by different starch levels: high starch (HS), medium starch (MS) and low starch, as the control diet (CT). Ruminal pH values were continuously measured using wireless sensors and compared with pH measurements obtained by rumenocentesis. Blood samples were analysed for complete blood count, biochemical profile, venous blood gas, blood lipopolysaccharide (LPS) and LPS-binding proteins (LBP). Results The regression coefficient comparing the ruminal pH values, obtained using the two methods, was 0.56 (P = 0.040). Feeding the CT, MS and HS led to differences in the time spent below the 5.8, 5.5 and 5.0 pH thresholds and in several variables, including dry matter intake (7.7 vs. 6.9 vs. 5.1 kg/d; P = 0.002), ruminal nadir pH (5.69 vs. 5.47 vs. 5.44; P = 0.042), mean ruminal pH (6.50 vs. 6.34 vs. 6.31; P = 0.012), haemoglobin level (11.1 vs. 10.9 vs. 11.4 g/dL; P = 0.010), platelet count (506 vs. 481 vs. 601; P = 0.008), HCO3- (31.8 vs. 31.3 vs. 30.6 mmol/L; P = 0.071) and LBP (5.9 vs. 9.5 vs. 10.5 μg/mL; P < 0.001). A canonical discriminant analysis (CDA) was used to classify the animals into four ruminal pH classes (normal, risk of acidosis, subacute ruminal acidosis and acute ruminal acidosis) using haemoglobin, mean platelet volume, β-hydroxybutyrate, glucose and reduced haemoglobin. Conclusions Although additional studies are necessary to confirm the reliability of these discriminant functions, the use of plasma variables in a multifactorial model appeared to be useful for the evaluation of ruminal acidosis severity. PMID:23647881

Effect of induced ruminal acidosis on blood variables in heifers.

PubMed

Marchesini, Giorgio; De Nardi, Roberta; Gianesella, Matteo; Stefani, Anna-Lisa; Morgante, Massimo; Barberio, Antonio; Andrighetto, Igino; Segato, Severino

2013-05-06

Ruminal acidosis is responsible for the onset of different pathologies in dairy and feedlot cattle, but there are major difficulties in the diagnosis. This study modelled the data obtained from various blood variables to identify those that could indicate the severity of ruminal acidosis. Six heifers were fed three experimental rations throughout three periods. The diets were characterised by different starch levels: high starch (HS), medium starch (MS) and low starch, as the control diet (CT). Ruminal pH values were continuously measured using wireless sensors and compared with pH measurements obtained by rumenocentesis. Blood samples were analysed for complete blood count, biochemical profile, venous blood gas, blood lipopolysaccharide (LPS) and LPS-binding proteins (LBP). The regression coefficient comparing the ruminal pH values, obtained using the two methods, was 0.56 (P = 0.040). Feeding the CT, MS and HS led to differences in the time spent below the 5.8, 5.5 and 5.0 pH thresholds and in several variables, including dry matter intake (7.7 vs. 6.9 vs. 5.1 kg/d; P = 0.002), ruminal nadir pH (5.69 vs. 5.47 vs. 5.44; P = 0.042), mean ruminal pH (6.50 vs. 6.34 vs. 6.31; P = 0.012), haemoglobin level (11.1 vs. 10.9 vs. 11.4 g/dL; P = 0.010), platelet count (506 vs. 481 vs. 601; P = 0.008), HCO3(-) (31.8 vs. 31.3 vs. 30.6 mmol/L; P = 0.071) and LBP (5.9 vs. 9.5 vs. 10.5 μg/mL; P < 0.001). A canonical discriminant analysis (CDA) was used to classify the animals into four ruminal pH classes (normal, risk of acidosis, subacute ruminal acidosis and acute ruminal acidosis) using haemoglobin, mean platelet volume, β-hydroxybutyrate, glucose and reduced haemoglobin. Although additional studies are necessary to confirm the reliability of these discriminant functions, the use of plasma variables in a multifactorial model appeared to be useful for the evaluation of ruminal acidosis severity.

Atypical MR lenticular signal change in infantile isovaleric acidemia.

PubMed

Wani, Nisar A; Qureshi, Umer Amin; Jehangir, Majid; Ahmad, Kaiser; Hussain, Zahid

2016-01-01

Isovaleric acidemia (IVA) is an inborn error of branched chain amino acid metabolism that may manifest as acute neonatal metabolic acidosis or as chronic intermittent form with developmental delay or recurrent episodes of acute metabolic acidosis. Early diagnosis is the key to prevent morbidity and mortality. Brain imaging abnormalities are rarely described in IVA. We report a case of chronic intermittent IVA with acute presentation in a 4-month-old infant who presented with acute metabolic acidosis. Brain magnetic resonance imaging (MRI) revealed symmetric signal intensity changes in bilateral lentiform nuclei with an unreported T1-weighted (T1W) symmetric hyperintense ring-like appearance in bilateral putamen.

Extracorporeal treatment with high-volume continuous venovenous hemodiafiltration and charcoal-based sorbent hemoperfusion for severe metformin-associated lactic acidosis

PubMed Central

Garg, Suneel Kumar; Singh, Omender; Deepak, Desh; Singh, Akhilesh; Yadav, Rohit; Vashist, Kirti

2016-01-01

We present a case of a 49-year-old female with an alleged history of ingestion of approximately 100 tablets of metformin (850 mg each). Investigations revealed severe lactic acidosis with lactate levels of 13.5 mmol/L and pH of 7.17. This indicates severe toxicity and is associated with a high mortality. Charcoal-based sorbent hemoperfusion was done as a desperate effort, as patient continued to deteriorate despite supportive care and high-volume continuous venovenous hemodiafiltration. The patient survived despite metformin-associated lactic acidosis related to severe metformin toxicity. PMID:27275079

Severity of acidosis affects long-term survival in COPD patients with hypoxemia after intensive care unit discharge.

PubMed

Gungor, Sinem; Kargin, Feyza; Irmak, Ilim; Ciyiltepe, Fulya; Acartürk Tunçay, Eylem; Atagun Guney, Pinar; Aksoy, Emine; Ocakli, Birsen; Adiguzel, Nalan; Karakurt, Zuhal

2018-01-01

Patients admitted to the intensive care unit (ICU) with acute respiratory failure (ARF) due to COPD have high mortality and morbidity. Acidosis has several harmful effects on hemodynamics and metabolism, and the current knowledge regarding the relationship between respiratory acidosis severity on the short- and long-term survival of COPD patients is limited. We hypothesized that COPD patients with severe acidosis would have a poorer short- and long-term prognosis compared with COPD patients with mild-to-moderate acidosis. This retrospective observational cohort study was conducted in a level III respiratory ICU of a tertiary teaching hospital for chest diseases between December 1, 2013, and December 30, 2014. Subject characteristics, comorbidities, ICU parameters, duration of mechanical ventilation, length of ICU stay, ICU mortality, use of domiciliary noninvasive mechanical ventilation (NIMV) and long-term oxygen therapy (LTOT), and short- and long-term mortality were recorded. Patients were grouped according to their arterial blood gas (ABG) values during ICU admission: severe acidotic (pH≤7.20) and mild-to-moderate acidotic (pH 7.21-7.35). These groups were compared with the recorded data. The mortality predictors were analyzed by logistic regression test in the ICU and the Cox regression test for long-term mortality predictors. During the study period, a total of 312 COPD patients admitted to the ICU with ARF, 69 (72.5% male) in the severe acidosis group and 243 (79% male) in the mild-to-moderate acidosis group, were enrolled. Group demographics, comorbidities, duration of mechanical ventilation, and length of ICU stay were similar in the two groups. The severe acidosis group had a significantly higher rate of NIMV failure (60.7% vs 40%) in the ICU. Mild-to-moderate acidotic COPD patients using LTOT had longer survival after ICU discharge than those without LTOT. On the other hand, severely acidotic COPD patients without LTOT showed shorter survival than those with LTOT. Kaplan-Meier cumulative survival analysis showed that the 28-day and 1-, 2-, and 3-year mortality rates were 12.2%, 36.2%, 52.6%, 63.3%, respectively ( p =0.09). The Cox regression analyses showed that older age, PaO 2 /FiO 2 <300 mmHg, and body mass index ≤20 kg/m 2 was associated with mortality of all patients after 3 years. Severely acidotic COPD patients had a poorer short- and long-term prognosis compared with mild-to-moderate acidotic COPD patients if acute and chronic hypoxemia was predominant.

Severity of acidosis affects long-term survival in COPD patients with hypoxemia after intensive care unit discharge

PubMed Central

Gungor, Sinem; Kargin, Feyza; Irmak, Ilim; Ciyiltepe, Fulya; Acartürk Tunçay, Eylem; Atagun Guney, Pinar; Aksoy, Emine; Ocakli, Birsen; Adiguzel, Nalan; Karakurt, Zuhal

2018-01-01

Background Patients admitted to the intensive care unit (ICU) with acute respiratory failure (ARF) due to COPD have high mortality and morbidity. Acidosis has several harmful effects on hemodynamics and metabolism, and the current knowledge regarding the relationship between respiratory acidosis severity on the short- and long-term survival of COPD patients is limited. We hypothesized that COPD patients with severe acidosis would have a poorer short- and long-term prognosis compared with COPD patients with mild-to-moderate acidosis. Patients and methods This retrospective observational cohort study was conducted in a level III respiratory ICU of a tertiary teaching hospital for chest diseases between December 1, 2013, and December 30, 2014. Subject characteristics, comorbidities, ICU parameters, duration of mechanical ventilation, length of ICU stay, ICU mortality, use of domiciliary noninvasive mechanical ventilation (NIMV) and long-term oxygen therapy (LTOT), and short- and long-term mortality were recorded. Patients were grouped according to their arterial blood gas (ABG) values during ICU admission: severe acidotic (pH≤7.20) and mild-to-moderate acidotic (pH 7.21–7.35). These groups were compared with the recorded data. The mortality predictors were analyzed by logistic regression test in the ICU and the Cox regression test for long-term mortality predictors. Results During the study period, a total of 312 COPD patients admitted to the ICU with ARF, 69 (72.5% male) in the severe acidosis group and 243 (79% male) in the mild-to-moderate acidosis group, were enrolled. Group demographics, comorbidities, duration of mechanical ventilation, and length of ICU stay were similar in the two groups. The severe acidosis group had a significantly higher rate of NIMV failure (60.7% vs 40%) in the ICU. Mild-to-moderate acidotic COPD patients using LTOT had longer survival after ICU discharge than those without LTOT. On the other hand, severely acidotic COPD patients without LTOT showed shorter survival than those with LTOT. Kaplan–Meier cumulative survival analysis showed that the 28-day and 1-, 2-, and 3-year mortality rates were 12.2%, 36.2%, 52.6%, 63.3%, respectively (p=0.09). The Cox regression analyses showed that older age, PaO2/FiO2 <300 mmHg, and body mass index ≤20 kg/m2 was associated with mortality of all patients after 3 years. Conclusion Severely acidotic COPD patients had a poorer short- and long-term prognosis compared with mild-to-moderate acidotic COPD patients if acute and chronic hypoxemia was predominant. PMID:29780244

Variation of bacterial communities and expression of Toll-like receptor genes in the rumen of steers differing in susceptibility to subacute ruminal acidosis.

PubMed

Chen, Yanhong; Oba, Masahito; Guan, Le Luo

2012-10-12

In order to determine differences in the ruminal bacterial community and host Toll-like receptor (TLR) gene expression of beef cattle with different susceptibility to acidosis, rumen papillae and content were collected from acidosis-susceptible (AS, n=3) and acidosis-resistant (AR, n=3) steers. The ruminal bacterial community was characterized using PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and quantitative real time PCR (qRT-PCR) analysis. Global R analysis of bacterial profile similarity revealed that bacterial diversity was significantly different between AR and AS groups for both rumen content (P=0.001) and epithelial (P=0.002) communities. The copy number of total bacterial 16S rRNA genes in content of AS steers was 10-fold higher than that of AR steers, and the copy number of total 16S rRNA genes of epimural bacteria in AR steers was positively correlated with ruminal pH (r=0.59, P=0.04), and negatively correlated with total VFA concentration (r=-0.59, P=0.05). The expressions of host TLR2 and 4 genes were significantly higher in AR steers compared to those in AS steers. These findings enhance our understanding about the ruminal microbial ecology and host gene expression changes that may be useful in the prevention of ruminal acidosis. Copyright © 2012 Elsevier B.V. All rights reserved.

Can nifekalant hydrochloride be used as a first-line drug for cardiopulmonary arrest (CPA)? : comparative study of out-of-hospital CPA with acidosis and in-hospital CPA without acidosis.

PubMed

Yoshioka, Koichiro; Amino, Mari; Morita, Seiji; Nakagawa, Yoshihide; Usui, Kazutane; Sugimoto, Atsuhiko; Matsuzaki, Atsushi; Deguchi, Yoshiaki; Yamamoto, Isotoshi; Inokuchi, Sadaki; Ikari, Yuji; Kodama, Itsuo; Tanabe, Teruhisa

2006-01-01

Early defibrillation of ventricular tachycardia and fibrillation (VT/VF) is an urgent and most important method of resuscitation for survival in cardiopulmonary arrest (CPA). We have previously reported that nifekalant (NIF), a specific I(Kr) blocker developed in Japan, is effective for lidocaine (LID) resistant VT/VF in out-of-hospital CPA (OHCPA). However, little is known about the differences in the effect of NIF on OHCPA with acidosis and in-hospital CPA (IHCPA) without acidosis. The present study enrolled 91 cases of DC shock resistant VT/VF among 892 cases of CPA that occurred between June 2000 and May 2003. NIF was used (0.15-0.3 mg/kg) after LID according to the cardiopulmonary resuscitation (CPR) algorithm of Tokai University. The defibrillation rate was higher in the NIF group for both OHCPA and IHCPA than for LID alone, and the VT/VF rate reduction effect could be maintained even with acidosis. However, sinus bradycardia in OHCPA, and torsades de pointes in IHCPA were occasionally observed. These differences in adverse effects might be related to the amount of epinephrine, serum potassium levels, serum pH, and interaction with LID. NIF had a favorable defibrillating effect in both CPA groups, and it shows promise of becoming a first-line drug for CPR.

Localization and hormonal control of serine dehydratase during metabolic acidosis differ markedly from those of phosphoenolpyruvate carboxykinase in rat kidney.

PubMed

Masuda, Tohru; Ogawa, Hirofumi; Matsushima, Takako; Kawamata, Seiichi; Sasahara, Masakiyo; Kuroda, Kazunari; Suzuki, Yasuhiro; Takata, Yoshimi; Yamazaki, Mitsuaki; Takusagawa, Fusao; Pitot, Henry C

2003-08-01

Serine dehydratase (SDH) is abundant in the rat liver but scarce in the kidney. When administrated with dexamethasone, the renal SDH activity was augmented 20-fold, whereas the hepatic SDH activity was affected little. In situ hybridization and immunohistochemistry revealed that SDH was localized to the proximal straight tubule of the nephron. To address the role of this hormone, rats were made acidotic by gavage of NH(4)Cl. Twenty-two hours later, the SDH activity was increased three-fold along with a six-fold increment in the phosphoenolpyruvate carboxykinase (PEPCK) activity, a rate-limiting enzyme of gluconeogenesis. PEPCK, which is localized to the proximal tubules under the normal condition, spreads throughout the entire cortex to the outer medullary rays by acidosis, whereas SDH does not change regardless of treatment with dexamethasone or NH(4)Cl. When NH(4)Cl was given to adrenalectomized rats, in contrast to the SDH activity no longer increasing, the PEPCK activity responded to acidosis to the same extent as in the intact rats. A simultaneous administration of dexamethasone and NH(4)Cl into the adrenalectomized rats fully restored the SDH activity, demonstrating that the rise in the SDH activity during acidosis is primarily controlled by glucocorticoids. The present findings clearly indicate that the localization of SDH and its hormonal regulation during acidosis are strikingly different from those of PEPCK.

Acidic pH modulation of Na+ channels in trigeminal mesencephalic nucleus neurons.

PubMed

Kang, In-Sik; Cho, Jin-Hwa; Choi, In-Sun; Kim, Do-Yeon; Jang, Il-Sung

2016-12-07

Cell bodies of trigeminal mesencephalic nucleus (Vmes) neurons are located within the central nervous system, and therefore, peripheral as well as central acidosis can modulate the excitability of Vmes neurons. Here, we report the effect of acidic pH on voltage-gated Na channels in acutely isolated rat Vmes neurons using a conventional whole-cell patch clamp technique. Acidic pH (pH 6.0) slightly but significantly shifted both the activation and steady-state fast inactivation relationships toward depolarized potentials. However, acidic pH (pH 6.0) had a minor effect on the inactivation kinetics of voltage-gated Na channels. Less sensitivity of voltage-gated Na channels to acidic pH may allow Vmes neurons to transduce the precise proprioceptive information even under acidic pH conditions.

Severe Neonatal Presentation of Mitochondrial Citrate Carrier (SLC25A1) Deficiency.

PubMed

Smith, Amanda; McBride, Skye; Marcadier, Julien L; Michaud, Jean; Al-Dirbashi, Osama Y; Schwartzentruber, Jeremy; Beaulieu, Chandree L; Katz, Sherri L; Majewski, Jacek; Bulman, Dennis E; Geraghty, Michael T; Harper, Mary-Ellen; Chakraborty, Pranesh; Lines, Matthew A

2016-01-01

Mutations of the mitochondrial citrate carrier (CIC) SLC25A1 cause combined D-2- and L-2-hydroxyglutaric aciduria (DL-2HGA; OMIM #615182), a neurometabolic disorder characterized by developmental delay, hypotonia, and seizures. Here, we describe the female child of consanguineous parents who presented neonatally with lactic acidosis, periventricular frontal lobe cysts, facial dysmorphism, recurrent apneic episodes, and deficient complex IV (cytochrome c oxidase) activity in skeletal muscle. Exome sequencing revealed a homozygous SLC25A1 missense mutation [NM_005984.4: c.593G>A; p.(Arg198His)] of a ubiquitously conserved arginine residue putatively situated within the substrate-binding site I of CIC. Retrospective review of the patient's organic acids confirmed the D- and L-2-hydroxyglutaric aciduria typical of DL-2HGA to be present, although this was not appreciated on initial presentation. Cultured patient skin fibroblasts showed reduced survival in culture, diminished mitochondrial spare respiratory capacity, increased glycolytic flux, and normal mitochondrial bulk, inner membrane potential, and network morphology. Neither cell survival nor cellular respiratory parameters were improved by citrate supplementation, although oral citrate supplementation did coincide with amelioration of lactic acidosis and apneic attacks in the patient. This is the fifth clinical report of CIC deficiency to date. The clinical features in our patient suggest that this disorder, which can potentially be recognized either by molecular means or based on its characteristic organic aciduria, should be considered in the differential diagnosis of pyruvate dehydrogenase deficiency and respiratory chain disorders. One-Sentence Summary A novel homozygous missense substitution in SLC25A1 was identified in a neonate presenting with lactic acidosis, intracerebral cysts, and an apparent mitochondrial complex IV defect in muscle.

Development, implementation and outcome analysis of semi-automated alerts for metformin dose adjustment in hospitalized patients with renal impairment.

PubMed

Niedrig, David; Krattinger, Regina; Jödicke, Annika; Gött, Carmen; Bucklar, Guido; Russmann, Stefan

2016-10-01

Overdosing of the oral antidiabetic metformin in impaired renal function is an important contributory cause to life-threatening lactic acidosis. The presented project aimed to quantify and prevent this avoidable medication error in clinical practice. We developed and implemented an algorithm into a hospital's clinical information system that prospectively identifies metformin prescriptions if the estimated glomerular filtration rate is below 60 mL/min. Resulting real-time electronic alerts are sent to clinical pharmacologists and pharmacists, who validate cases in electronic medical records and contact prescribing physicians with recommendations if necessary. The screening algorithm has been used in routine clinical practice for 3 years and generated 2145 automated alerts (about 2 per day). Validated expert recommendations regarding metformin therapy, i.e., dose reduction or stop, were issued for 381 patients (about 3 per week). Follow-up was available for 257 cases, and prescribers' compliance with recommendations was 79%. Furthermore, during 3 years, we identified eight local cases of lactic acidosis associated with metformin therapy in renal impairment that could not be prevented, e.g., because metformin overdosing had occurred before hospitalization. Automated sensitive screening followed by specific expert evaluation and personal recommendations can prevent metformin overdosing in renal impairment with high efficiency and efficacy. Repeated cases of metformin-associated lactic acidosis in renal impairment underline the clinical relevance of this medication error. Our locally developed and customized alert system is a successful proof of concept for a proactive clinical drug safety program that is now expanded to other clinically and economically relevant medication errors. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Fludrocortisone therapy for persistent hyperkalaemia.

PubMed

Dobbin, S J H; Petrie, J R; Lean, M E J; McKay, G A

2017-07-01

Type 4 renal tubular acidosis causes hyperkalaemia, for which diabetes and medications commonly used in this patient group are aetiological factors. Here we describe the novel use of fludrocortisone in this difficult condition. A 55-year-old woman with complex co-morbidities, including Type 2 diabetes (HbA 1c 37 mmol/mol 5.5%), was admitted with renal failure. Bloods on admission: eGFR 25 ml/min, creatinine 184 ?mol/L, urea 35.9 mmol/L, sodium 128 mmol/L, potassium 5.6 mmol/L, bicarbonate 15 mmol/L, and albumin 30 g/L. Her admission was prolonged, complicated by hospital-acquired sepsis (lower respiratory tract, urinary tract, and infected leg ulcers), poor venous access and severe depression. She had recurrent hyperkalaemia and deteriorating renal function, from presumed Type 4 renal tubular acidosis and excessive fluid losses from leg ulcers. Her renal function recurrently deteriorated, despite conventional treatment methods. After 69 days, she was commenced on fludrocortisone 50 mcg/day. Her renal function and serum potassium stabilized and she was discharged with potassium 4.3 mmol/L, eGFR 42 ml/min, and bicarbonate 23 mmol/L. She has remained stable on this treatment, without requiring further hospital admission for over 6 months, with eGFR 40 ml/min, and potassium 5.5 mmol/L, and albumin 26 g/L. This woman was presumed to have Type 4 renal tubular acidosis and recurrent hyperkalaemia due to renal insufficiency, in the context of underlying diabetes and chronic kidney disease, which was poorly responsive to conventional management. There is limited evidence for using fludrocortisone in this setting. Our case suggests that fludrocortisone might offer a novel therapeutic strategy when conventional management is not working. © 2017 Diabetes UK.

Beneficial effect of pyruvate therapy on Leigh syndrome due to a novel mutation in PDH E1α gene.

PubMed

Koga, Yasutoshi; Povalko, Nataliya; Katayama, Koujyu; Kakimoto, Noriko; Matsuishi, Toyojiro; Naito, Etsuo; Tanaka, Masashi

2012-02-01

Leigh syndrome (LS) is a progressive untreatable degenerating mitochondrial disorder caused by either mitochondrial or nuclear DNA mutations. A patient was a second child of unconsanguineous parents. On the third day of birth, he was transferred to neonatal intensive care units because of severe lactic acidosis. Since he was showing continuous lactic acidosis, the oral supplementation of dichloroacetate (DCA) was introduced on 31st day of birth at initial dose of 50 mg/kg, followed by maintenance dose of 25 mg/kg/every 12 h. The patient was diagnosed with LS due to a point mutation of an A-C at nucleotide 599 in exon 6 in the pyruvate dehydrogenase E1α gene, resulting in the substitution of aspartate for threonine at position 200 (N200T). Although the concentrations of lactate and pyruvate in blood were slightly decreased, his clinical conditions were deteriorating progressively. In order to overcome the mitochondrial or cytosolic energy crisis indicated by lactic acidosis as well as clinical symptoms, we terminated the DCA and administered 0.5 g/kg/day TID of sodium pyruvate orally. We analyzed the therapeutic effects of DCA or sodium pyruvate in the patient, and found that pyruvate therapy significantly decreased lactate, pyruvate and alanine levels, showed no adverse effects such as severe neuropathy seen in DCA, and had better clinical response on development and epilepsy. Though the efficacy of pyruvate on LS will be evaluated by randomized double-blind placebo-controlled study design in future, pyruvate therapy is a possible candidate for therapeutic choice for currently incurable mitochondrial disorders such as LS. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high anion gap metabolic acidosis following paracetamol (acetaminophen) exposure?

PubMed

Liss, D B; Paden, M S; Schwarz, E S; Mullins, M E

2013-11-01

Paracetamol (acetaminophen) ingestion is the most frequent pharmaceutical overdose in the developed world. Metabolic acidosis sometimes occurs, but the acidosis is infrequently persistent or severe. A growing number of case reports and case series describe high anion gap metabolic acidosis (HAGMA) following paracetamol exposure with subsequent detection or measurement of 5-oxoproline (also called pyroglutamic acid) in blood, urine, or both. Typically 5-oxoprolinuria or 5-oxoprolinemia occurs in the setting of inborn genetic errors in glutathione metabolism. It is unknown whether 5-oxoprolinemia in the setting of paracetamol exposure reflects an acquired or transient derangement of glutathione metabolism or previously unrecognized genetic defects. We reviewed the published cases of 5-oxoprolinemia or 5-oxoprolinuria among patients with HAGMA in the setting of paracetamol exposure. Our goal was to identify any consistent features that might increase our understanding of the pathophysiology, diagnosis, and treatment of similar cases. We searched the medical literature using PUBMED and EMBASE from inception to 28 August 2013 applying search terms ("oxoproline" OR "pyroglutamic acid" AND "paracetamol" OR "acetaminophen"). The intersection of these two searches returned 77 articles, of which 64 involved human subjects and were in English. Two articles, one each in Spanish and Dutch, were reviewed. An additional Google Scholar search was done with the same terms. We manually searched the reference lists of retrieved articles to identify additional four relevant articles. We focused on articles including measured 5-oxoproline concentrations in urine or blood. Twenty-two articles included quantified 5-oxoproline concentrations. Several additional articles mentioned only qualitative detection of 5-oxoproline in urine or blood without concentrations being reported. Our manual reference search yielded four additional articles for a total of 24 articles describing 43 patients with quantified 5-oxoproline concentrations. The cases varied widely in paracetamol dose, duration and circumstances of paracetamol exposure, presence, and degree of elevation in transaminase activities, and when reported observed blood, serum, or urine 5-oxoproline concentrations. Concomitant use of flucloxacillin, another medication associated with oxoprolinemia or oxoprolinuria, confounded several of the cases. No clear dose-response relationship existed between the quantity of paracetamol ingested and the observed concentrations of 5-oxoproline. Clinical outcomes, including mortality, varied with no clear relationship to 5-oxoproline concentrations. In rare cases, HAGMA in the setting of paracetamol exposure is attributable to 5-oxoprolinemia. Clinicians should first exclude commoner and treatable causes of HAGMA, such as lactic acidosis, co-ingested drug administration, and ketoacidosis. It is likely that the propensity for HAGMA following paracetamol exposure may be genetically determined. The effects of acetylcysteine on 5-oxoproline concentrations or clinical outcome are unknown. When HAGMA is diagnosed, the 5-oxoproline concentration and the glutathione synthetase activity should be measured.

Individual animal variability in ruminal bacterial communities and ruminal acidosis in primiparous Holstein cows during the periparturient period

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to investigate variability among individual cows for their susceptibility to ruminal acidosis (RA) pre- and postpartum, and determine whether this variability was related to differences in their ruminal bacterial community composition (BCC). Variability in susceptibilit...

Uses and misuses of sodium bicarbonate in the neonatal intensive care unit.

PubMed

Collins, Amélie; Sahni, Rakesh

2017-10-01

Over the past several decades, bicarbonate therapy continues to be used routinely in the treatment of acute metabolic acidosis in critically ill neonates despite the lack of evidence for its effectiveness in the treatment of acid-base imbalance, and evidence indicating that it may be detrimental. Clinicians often feel compelled to use bicarbonate since acidosis implies a need for such therapy and thus the justification for its use is based on hearsay rather than science. This review summarizes the evidence and refutes the clinical practice of administering sodium bicarbonate to treat metabolic acidosis associated with several specific clinical syndromes in neonates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Propylene Glycol Poisoning From Excess Whiskey Ingestion: A Case of High Osmolal Gap Metabolic Acidosis.

PubMed

Cunningham, Courtney A; Ku, Kevin; Sue, Gloria R

2015-01-01

In this report, we describe a case of high anion gap metabolic acidosis with a significant osmolal gap attributed to the ingestion of liquor containing propylene glycol. Recently, several reports have characterized severe lactic acidosis occurring in the setting of iatrogenic unintentional overdosing of medications that use propylene glycol as a diluent, including lorazepam and diazepam. To date, no studies have explored potential effects of excess propylene glycol in the setting of alcohol intoxication. Our patient endorsed drinking large volumes of cinnamon flavored whiskey, which was likely Fireball Cinnamon Whisky. To our knowledge, this is the first case of propylene glycol toxicity from an intentional ingestion of liquor containing propylene glycol.

Septic Shock

PubMed Central

Lansing, Allan M.

1963-01-01

Septic shock may be defined as hypotension caused by bacteremia and accompanied by decreased peripheral blood flow, evidenced by oliguria. Clinically, a shaking chill is the warning signal. The immediate cause of hypotension is pooling of blood in the periphery, leading to decreased venous return: later, peripheral resistance falls and cardiac failure may occur. Irreversible shock is comparable to massive reactive hyperemia. Reticuloendothelial failure, histamine release, and toxic hypersensitivity may be factors in the pathogenesis of septic shock. Adrenal failure does not usually occur, but large doses of corticosteroid are employed therapeutically to counteract the effect of histamine release or hypersensitivity to endotoxin. The keys to successful therapy are time, antibiotics, vasopressors, cortisone and correction of acidosis. PMID:14063936

Hypokalemic muscular paralysis causing acute respiratory failure due to rhabdomyolysis with renal tubular acidosis in a chronic glue sniffer.

PubMed

Kao, K C; Tsai, Y H; Lin, M C; Huang, C C; Tsao, C Y; Chen, Y C

2000-01-01

A 34-year-old male was admitted to the emergency department with the development of quadriparesis and respiratory failure due to hypokalemia after prolonged glue sniffing. The patient was subsequently given mechanical ventilatory support for respiratory failure. He was weaned from the ventilator 4 days later after potassium replacement. Toluene is an aromatic hydrocarbon found in glues, cements, and solvents. It is known to be toxic to the nervous system, hematopoietic system, and causes acid-base and electrolyte disorders. Acute respiratory failure with hypokalemia and rhabdomyolysis with acute renal failure should be considered as potential events in a protracted glue sniffing.

Treatment options for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome.

PubMed

Santa, Kristin M

2010-11-01

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare neurodegenerative disease caused by the decreased ability of cells to produce sufficient energy in the form of adenosine 5'-triphosphate. Although it is one of the most common maternally inherited mitochondrial disorders, its exact incidence is unknown. Caused most frequently by an A-to-G point mutation at the 3243 position in the mitochondrial DNA, MELAS syndrome has a broad range of clinical manifestations and a highly variable course. The classic neurologic characteristics include encephalopathy, seizures, and stroke-like episodes. In addition to its neurologic manifestations, MELAS syndrome exhibits multisystem effects including cardiac conduction defects, diabetes mellitus, short stature, myopathy, and gastrointestinal disturbances. Unfortunately, no consensus guidelines outlining standard drug regimens exist for this syndrome. Many of the accepted therapies used in treating MELAS syndrome have been identified through a small number of clinical trials or isolated case reports. Currently, the drugs most often used include antioxidants and various vitamins aimed at minimizing the demands on the mitochondria and supporting and maximizing their function. Some of the most frequently prescribed agents include coenzyme Q(10), l-arginine, B vitamins, and levocarnitine. Although articles describing MELAS syndrome are available, few specifically target education for clinical pharmacists. This article will provide pharmacists with a practical resource to enhance their understanding of MELAS syndrome in order to provide safe and effective pharmaceutical care.

Milk and acid-base balance: proposed hypothesis versus scientific evidence.

PubMed

Fenton, Tanis R; Lyon, Andrew W

2011-10-01

Recently the lay press has claimed a hypothetical association among dairy product consumption, generation of dietary acid, and harm to human health. This theoretical association is based on the idea that the protein and phosphate in milk and dairy products make them acid-producing foods, which cause our bodies to become acidified, promoting diseases of modern civilization. Some authors have suggested that dairy products are not helpful and perhaps detrimental to bone health because higher osteoporotic fracture incidence is observed in countries with higher dairy product consumption. However, scientific evidence does not support any of these claims. Milk and dairy products neither produce acid upon metabolism nor cause metabolic acidosis, and systemic pH is not influenced by diet. Observations of higher dairy product intake in countries with prevalent osteoporosis do not hold when urban environments are compared, likely due to physical labor in rural locations. Milk and other dairy products continue to be a good source of dietary protein and other nutrients. Key teaching points: Measurement of an acidic pH urine does not reflect metabolic acidosis or an adverse health condition. The modern diet, and dairy product consumption, does not make the body acidic. Alkaline diets alter urine pH but do not change systemic pH. Net acid excretion is not an important influence of calcium metabolism. Milk is not acid producing. Dietary phosphate does not have a negative impact on calcium metabolism, which is contrary to the acid-ash hypothesis.

[A man with a classic serious milk-alkali syndrome and a carcinoma of the stomach].

PubMed

Verburg, F A J; van Zanten, R A A; Brouwer, R M L; Woittiez, A J J; Veneman, Th F

2006-07-22

A 42-year-old man was transferred to the Emergency Department after his friends had found him unresponsive and confused in his room. He had been experiencing upper abdominal complaints for a period of several months. He had taken large amounts of a calcium carbonate/magnesium subcarbonate preparation (Rennie) and had consumed at least 3 litres of dairy products per day. His behaviour was reported as being more and more abnormal during the previous few weeks. On admission he was confused and agitated and had involuntary movements of his limbs. Laboratory investigation indicated a triple acid base disorder, i.e. metabolic alkalosis, respiratory alkalosis and high anion gap metabolic acidosis, with severe dehydration. The metabolic alkalosis was caused by the intake of large amounts of dairy and antacids: milk-alkali syndrome. The metabolic acidosis was the result of hypovolaemia and pre-renal renal failure and the respiratory alkalosis was caused by hyperventilation due to the organic psychosyndrome. The patient was treated with volume expansion by isotonic saline and the administration of potassium and he was sedated with low-dose midazolam, which led to a full respiratory compensation of the metabolic alkalosis. A few days following admission, both the plasma calcium concentration and renal function returned to normal; the acid-base disorder completely normalized and the organic psychosyndrome disappeared. On gastroduodenoscopy a gastric ulcer was found; biopsies revealed a signet ring cell adenocarcinoma of the stomach.

Dietary management of D-lactic acidosis in short bowel syndrome.

PubMed Central

Mayne, A J; Handy, D J; Preece, M A; George, R H; Booth, I W

1990-01-01

Manipulation of carbohydrate intake was used to treat severe, recurrent D-lactic acidosis in a patient with short bowel syndrome. Dietary carbohydrate composition was determined after assessment of D-lactic acid production from various carbohydrate substrates by faecal flora in vitro. This approach may be preferable to repeated courses of antibiotics. PMID:2317072

Severe lactic acidosis and acute renal failure following ingestion of metformin and kerosene oil: a case report.

PubMed

Rathnapala, Amila; Matthias, Thushara; Jayasinghe, Saroj

2012-01-17

Kerosene is a freely accessible hydrocarbon used in Sri Lankan (and other Asian) households for cooking and for lighting lamps. Kerosene poisoning is rarely reported among adults and its toxicological effects are not well known. Metformin is a commonly used oral hypoglycemic drug and its overdose leads primarily to lactic acidosis. Combined poisoning of metformin and kerosene and their interactions have not been reported. An 18-year-old, previously healthy, unmarried Sinhalese woman was referred following ingestion of 17.5 g of metformin and approximately 200 mL of kerosene oil in a suicide attempt. She had vomiting, burning epigastric pain, and a hypoglycemic seizure (capillary blood glucose of 42 mg/dL). Subsequently, she developed severe lactic acidosis followed by acute renal insufficiency, was treated with sodium bicarbonate, and underwent intermittent hemodialysis with bicarbonate. She recovered completely. This report proposes possible interactions that occur between metformin and kerosene that augment toxicity when the two are ingested together. It also stresses the importance of early treatment with intermittent hemodialysis in severe lactic acidosis with maintenance of blood glucose.

Severe metabolic acidosis in adult patients with Duchenne muscular dystrophy.

PubMed

Lo Cascio, Christian M; Latshang, Tsogyal D; Kohler, Malcolm; Fehr, Thomas; Bloch, Konrad E

2014-01-01

Duchenne muscular dystrophy (DMD) leads to progressive paresis, respiratory failure and premature death. Long-term positive pressure ventilation can improve quality of life and survival, but previously unrecognized complications may arise. We analyzed the characteristics of severe metabolic acidosis occurring in 8 of 55 DMD patients, of 20-36 years of age, observed over a 5-year period. All patients were on positive pressure ventilation and were being treated for chronic constipation. Before admission, they had had a reduced intake of fluids and food. Upon examination, they were severely ill, dyspneic and suffering from abdominal discomfort. Metabolic acidosis with a high anion gap was noted in 5 of the 8 patients and with a normal anion gap in the other 3. They all recovered after the administration of fluids and nutrition, the regulation of bowel movements and treatment with antibiotics, as appropriate. Metabolic acidosis is a life-threatening, potentially preventable complication in older DMD patients. Early recognition, subsequent administration of fluids, nutrition and antibiotics and regulation of bowel movements seem to be essential. © 2014 S. Karger AG, Basel.

Cerebral lactic acidosis correlates with neurological impairment in MELAS.

PubMed

Kaufmann, P; Shungu, D C; Sano, M C; Jhung, S; Engelstad, K; Mitsis, E; Mao, X; Shanske, S; Hirano, M; DiMauro, S; De Vivo, D C

2004-04-27

To evaluate the role of chronic cerebral lactic acidosis in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). The authors studied 91 individuals from 34 families with MELAS and the A3243G point mutation and 15 individuals from two families with myoclonus epilepsy and ragged red fibers (MERRF) and the A8344G mutation. Subjects were divided into four groups. Paternal relatives were studied as controls (Group 1). The maternally related subjects were divided clinically into three groups: asymptomatic (no clinical evidence of neurologic disease) (Group 2), oligosymptomatic (neurologic symptoms but without the full clinical picture of MELAS or MERRF) (Group 3), and symptomatic (fulfilling MELAS or MERRF criteria) (Group 4). The authors performed a standardized neurologic examination, neuropsychological testing, MRS, and leukocyte DNA analysis in all subjects. The symptomatic and oligosymptomatic MELAS subjects had significantly higher ventricular lactate than the other groups. There was a significant correlation between degree of neuropsychological and neurologic impairment and cerebral lactic acidosis as estimated by ventricular MRS lactate levels. High levels of ventricular lactate, the brain spectroscopic signature of MELAS, are associated with more severe neurologic impairment.

Phenylbutyrate Therapy for Pyruvate Dehydrogenase Complex Deficiency and Lactic Acidosis

PubMed Central

Ferriero, Rosa; Manco, Giuseppe; Lamantea, Eleonora; Nusco, Edoardo; Ferrante, Mariella I.; Sordino, Paolo; Stacpoole, Peter W.; Lee, Brendan; Zeviani, Massimo; Brunetti-Pierri, Nicola

2014-01-01

Lactic acidosis is a build-up of lactic acid in the blood and tissues, which can be due to several inborn errors of metabolism as well as nongenetic conditions. Deficiency of pyruvate dehydrogenase complex (PDHC) is the most common genetic disorder leading to lactic acidosis. Phosphorylation of specific serine residues of the E1α subunit of PDHC by pyruvate dehydrogenase kinase (PDK) inactivates the enzyme, whereas dephosphorylation restores PDHC activity. We found that phenylbutyrate enhances PDHC enzymatic activity in vitro and in vivo by increasing the proportion of unphosphorylated enzyme through inhibition of PDK. Phenylbutyrate given to C57B6/L wild-type mice results in a significant increase in PDHC enzyme activity and a reduction of phosphorylated E1α in brain, muscle, and liver compared to saline-treated mice. By means of recombinant enzymes, we showed that phenylbutyrate prevents phosphorylation of E1α through binding and inhibition of PDK, providing a molecular explanation for the effect of phenylbutyrate on PDHC activity. Phenylbutyrate increases PDHC activity in fibroblasts from PDHC-deficient patients harboring various molecular defects and corrects the morphological, locomotor, and biochemical abnormalities in the noam631 zebrafish model of PDHC deficiency. In mice, phenylbutyrate prevents systemic lactic acidosis induced by partial hepatectomy. Because phenylbutyrate is already approved for human use in other diseases, the findings of this study have the potential to be rapidly translated for treatment of patients with PDHC deficiency and other forms of primary and secondary lactic acidosis. PMID:23467562

Proteomic profiling and pathway analysis of the response of rat renal proximal convoluted tubules to metabolic acidosis

PubMed Central

Schauer, Kevin L.; Freund, Dana M.; Prenni, Jessica E.

2013-01-01

Metabolic acidosis is a relatively common pathological condition that is defined as a decrease in blood pH and bicarbonate concentration. The renal proximal convoluted tubule responds to this condition by increasing the extraction of plasma glutamine and activating ammoniagenesis and gluconeogenesis. The combined processes increase the excretion of acid and produce bicarbonate ions that are added to the blood to partially restore acid-base homeostasis. Only a few cytosolic proteins, such as phosphoenolpyruvate carboxykinase, have been determined to play a role in the renal response to metabolic acidosis. Therefore, further analysis was performed to better characterize the response of the cytosolic proteome. Proximal convoluted tubule cells were isolated from rat kidney cortex at various times after onset of acidosis and fractionated to separate the soluble cytosolic proteins from the remainder of the cellular components. The cytosolic proteins were analyzed using two-dimensional liquid chromatography and tandem mass spectrometry (MS/MS). Spectral counting along with average MS/MS total ion current were used to quantify temporal changes in relative protein abundance. In all, 461 proteins were confidently identified, of which 24 exhibited statistically significant changes in abundance. To validate these techniques, several of the observed abundance changes were confirmed by Western blotting. Data from the cytosolic fractions were then combined with previous proteomic data, and pathway analyses were performed to identify the primary pathways that are activated or inhibited in the proximal convoluted tubule during the onset of metabolic acidosis. PMID:23804448

Low-flow CO₂ removal integrated into a renal-replacement circuit can reduce acidosis and decrease vasopressor requirements.

PubMed

Forster, Christian; Schriewer, Jens; John, Stefan; Eckardt, Kai-Uwe; Willam, Carsten

2013-07-24

Lung-protective ventilation in patients with ARDS and multiorgan failure, including renal failure, is often paralleled with a combined respiratory and metabolic acidosis. We assessed the effectiveness of a hollow-fiber gas exchanger integrated into a conventional renal-replacement circuit on CO₂ removal, acidosis, and hemodynamics. In ten ventilated critically ill patients with ARDS and AKI undergoing renal- and respiratory-replacement therapy, effects of low-flow CO₂ removal on respiratory acidosis compensation were tested by using a hollow-fiber gas exchanger added to the renal-replacement circuit. This was an observational study on safety, CO₂-removal capacity, effects on pH, ventilator settings, and hemodynamics. CO₂ elimination in the low-flow circuit was safe and was well tolerated by all patients. After 4 hours of treatment, a mean reduction of 17.3 mm Hg (-28.1%) pCO₂ was observed, in line with an increase in pH. In hemodynamically instable patients, low-flow CO₂ elimination was paralleled by hemodynamic improvement, with an average reduction of vasopressors of 65% in five of six catecholamine-dependent patients during the first 24 hours. Because no further catheters are needed, besides those for renal replacement, the implementation of a hollow-fiber gas exchanger in a renal circuit could be an attractive therapeutic tool with only a little additional trauma for patients with mild to moderate ARDS undergoing invasive ventilation with concomitant respiratory acidosis, as long as no severe oxygenation defects indicate ECMO therapy.

Central Fetal Monitoring With and Without Computer Analysis: A Randomized Controlled Trial.

PubMed

Nunes, Inês; Ayres-de-Campos, Diogo; Ugwumadu, Austin; Amin, Pina; Banfield, Philip; Nicoll, Antony; Cunningham, Simon; Sousa, Paulo; Costa-Santos, Cristina; Bernardes, João

2017-01-01

To evaluate whether intrapartum fetal monitoring with computer analysis and real-time alerts decreases the rate of newborn metabolic acidosis or obstetric intervention when compared with visual analysis. A randomized clinical trial carried out in five hospitals in the United Kingdom evaluated women with singleton, vertex fetuses of 36 weeks of gestation or greater during labor. Continuous central fetal monitoring by computer analysis and online alerts (experimental arm) was compared with visual analysis (control arm). Fetal blood sampling and electrocardiographic ST waveform analysis were available in both arms. The primary outcome was incidence of newborn metabolic acidosis (pH less than 7.05 and base deficit greater than 12 mmol/L). Prespecified secondary outcomes included operative delivery, use of fetal blood sampling, low 5-minute Apgar score, neonatal intensive care unit admission, hypoxic-ischemic encephalopathy, and perinatal death. A sample size of 3,660 per group (N=7,320) was planned to be able to detect a reduction in the rate of metabolic acidosis from 2.8% to 1.8% (two-tailed α of 0.05 with 80% power). From August 2011 through July 2014, 32,306 women were assessed for eligibility and 7,730 were randomized: 3,961 to computer analysis and online alerts, and 3,769 to visual analysis. Baseline characteristics were similar in both groups. Metabolic acidosis occurred in 16 participants (0.40%) in the experimental arm and 22 participants (0.58%) in the control arm (relative risk 0.69 [0.36-1.31]). No statistically significant differences were found in the incidence of secondary outcomes. Compared with visual analysis, computer analysis of fetal monitoring signals with real-time alerts did not significantly reduce the rate of metabolic acidosis or obstetric intervention. A lower-than-expected rate of newborn metabolic acidosis was observed in both arms of the trial. ISRCTN Registry, http://www.isrctn.com, ISRCTN42314164.

Sodium bicarbonate use and the risk of hypernatremia in thoracic aortic surgical patients with metabolic acidosis following deep hypothermic circulatory arrest

PubMed Central

Ghadimi, Kamrouz; Gutsche, Jacob T.; Ramakrishna, Harish; Setegne, Samuel L.; Jackson, Kirk R.; Augoustides, John G.; Ochroch, E. Andrew; Weiss, Stuart J.; Bavaria, Joseph E.; Cheung, Albert T.

2016-01-01

Objective: Metabolic acidosis after deep hypothermic circulatory arrest (DHCA) for thoracic aortic operations is commonly managed with sodium bicarbonate (NaHCO3). The purpose of this study was to determine the relationships between total NaHCO3 dose and the severity of metabolic acidosis, duration of mechanical ventilation, duration of vasoactive infusions, and Intensive Care Unit (ICU) or hospital length of stay (LOS). Methods: In a single center, retrospective study, 87 consecutive elective thoracic aortic operations utilizing DHCA, were studied. Linear regression analysis was used to test for the relationships between the total NaHCO3 dose administered through postoperative day 2, clinical variables, arterial blood gas values, and short-term clinical outcomes. Results: Seventy-five patients (86%) received NaHCO3. Total NaHCO3 dose averaged 136 ± 112 mEq (range: 0.0–535 mEq) per patient. Total NaHCO3 dose correlated with minimum pH (r = 0.41, P < 0.0001), minimum serum bicarbonate (r = −0.40, P < 0.001), maximum serum lactate (r = 0.46, P = 0.007), duration of metabolic acidosis (r = 0.33, P = 0.002), and maximum serum sodium concentrations (r = 0.29, P = 0.007). Postoperative hypernatremia was present in 67% of patients and peaked at 12 h following DHCA. Eight percent of patients had a serum sodium ≥ 150 mEq/L. Total NaHCO3 dose did not correlate with anion gap, serum chloride, not the duration of mechanical ventilator support, vasoactive infusions, ICU or hospital LOS. Conclusion: Routine administration of NaHCO3 was common for the management of metabolic acidosis after DHCA. Total dose of NaHCO3 was a function of the severity and duration of metabolic acidosis. NaHCO3 administration contributed to postoperative hypernatremia that was often severe. The total NaHCO3 dose administered was unrelated to short-term clinical outcomes. PMID:27397449

Prevalence and magnitude of acidosis sequelae to rice-based feeding regimen followed in Tamil Nadu, India.

PubMed

Murugeswari, Rathinam; Valli, Chinnamani; Karunakaran, Raman; Leela, Venkatasubramanian; Pandian, Amaresan Serma Saravana

2018-04-01

In Tamil Nadu, a southern state of India, rice is readily available at a low cost, hence, is cooked (cooking akin to human consumption) and fed irrationally to cross-bred dairy cattle with poor productivity. Hence, a study was carried out with the objective to examine the prevalence of acidosis sequelae to rice-based feeding regimen and assess its magnitude. A survey was conducted in all the 32 districts of Tamil Nadu, by randomly selecting two blocks per districts and from each block five villages were randomly selected. From each of the selected village, 10 dairy farmers belonging to the unorganized sector, owning one or two cross-bred dairy cows in early and mid-lactation were randomly selected so that a sample size of 100 farmers per district was maintained. The feeding regimen, milk yield was recorded, and occurrence of acidosis and incidence of laminitis were ascertained by the veterinarian with the confirmative test to determine the impact of feeding cooked rice to cows. It is observed that 71.5% of farmers in unorganized sector feed cooked rice to their cattle. The incidence of acidosis progressively increased significantly (p<0.05) from 29.00% in cows fed with 0.5 kg of cooked rice to 69.23% in cows fed with more than 2.5 kg of cooked rice. However, the incidence of acidosis remained significantly (p<0.05) as low as 9.9% in cows fed feeding regimen without cooked rice which is suggestive of a correlation between excessive feeding cooked rice and onset of acidosis. Further, the noticeable difference in the incidence of acidosis observed between feeding cooked rice and those fed without rice and limited intake of oil cake indicates that there is a mismatch between energy and protein supply to these cattle. Among cooked rice-based diet, the incidence of laminitis increased progressively (p<0.05) from 9.2% to 37.9% with the increase in the quantum of cooked rice in the diet. The study points out the importance of protein supplementation in rice-based feeding regimen to set right the mismatched supply between nitrogen and fermentable organic matter in the rumen. This research has practical implications for animal health, welfare, nutrition, and management.

Prevalence and magnitude of acidosis sequelae to rice-based feeding regimen followed in Tamil Nadu, India

PubMed Central

Murugeswari, Rathinam; Valli, Chinnamani; Karunakaran, Raman; Leela, Venkatasubramanian; Pandian, Amaresan Serma Saravana

2018-01-01

Background and Aim In Tamil Nadu, a southern state of India, rice is readily available at a low cost, hence, is cooked (cooking akin to human consumption) and fed irrationally to cross-bred dairy cattle with poor productivity. Hence, a study was carried out with the objective to examine the prevalence of acidosis sequelae to rice-based feeding regimen and assess its magnitude. Materials and Methods A survey was conducted in all the 32 districts of Tamil Nadu, by randomly selecting two blocks per districts and from each block five villages were randomly selected. From each of the selected village, 10 dairy farmers belonging to the unorganized sector, owning one or two cross-bred dairy cows in early and mid-lactation were randomly selected so that a sample size of 100 farmers per district was maintained. The feeding regimen, milk yield was recorded, and occurrence of acidosis and incidence of laminitis were ascertained by the veterinarian with the confirmative test to determine the impact of feeding cooked rice to cows. Results It is observed that 71.5% of farmers in unorganized sector feed cooked rice to their cattle. The incidence of acidosis progressively increased significantly (p<0.05) from 29.00% in cows fed with 0.5 kg of cooked rice to 69.23% in cows fed with more than 2.5 kg of cooked rice. However, the incidence of acidosis remained significantly (p<0.05) as low as 9.9% in cows fed feeding regimen without cooked rice which is suggestive of a correlation between excessive feeding cooked rice and onset of acidosis. Further, the noticeable difference in the incidence of acidosis observed between feeding cooked rice and those fed without rice and limited intake of oil cake indicates that there is a mismatch between energy and protein supply to these cattle. Among cooked rice-based diet, the incidence of laminitis increased progressively (p<0.05) from 9.2% to 37.9% with the increase in the quantum of cooked rice in the diet. Conclusion The study points out the importance of protein supplementation in rice-based feeding regimen to set right the mismatched supply between nitrogen and fermentable organic matter in the rumen. This research has practical implications for animal health, welfare, nutrition, and management PMID:29805211

Construction and validation of a decision tree for treating metabolic acidosis in calves with neonatal diarrhea

PubMed Central

2012-01-01

Background The aim of the present prospective study was to investigate whether a decision tree based on basic clinical signs could be used to determine the treatment of metabolic acidosis in calves successfully without expensive laboratory equipment. A total of 121 calves with a diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital were included in the study. The dosages of sodium bicarbonate administered followed simple guidelines based on the results of a previous retrospective analysis. Calves that were neither dehydrated nor assumed to be acidemic received an oral electrolyte solution. In cases in which intravenous correction of acidosis and/or dehydration was deemed necessary, the provided amount of sodium bicarbonate ranged from 250 to 750 mmol (depending on alterations in posture) and infusion volumes from 1 to 6.25 liters (depending on the degree of dehydration). Individual body weights of calves were disregarded. During the 24 hour study period the investigator was blinded to all laboratory findings. Results After being lifted, many calves were able to stand despite base excess levels below −20 mmol/l. Especially in those calves, metabolic acidosis was undercorrected with the provided amount of 500 mmol sodium bicarbonate, which was intended for calves standing insecurely. In 13 calves metabolic acidosis was not treated successfully as defined by an expected treatment failure or a measured base excess value below −5 mmol/l. By contrast, 24 hours after the initiation of therapy, a metabolic alkalosis was present in 55 calves (base excess levels above +5 mmol/l). However, the clinical status was not affected significantly by the metabolic alkalosis. Conclusions Assuming re-evaluation of the calf after 24 hours, the tested decision tree can be recommended for the use in field practice with minor modifications. Calves that stand insecurely and are not able to correct their position if pushed require higher doses of sodium bicarbonate, if there is clinical evidence of a marked D-lactic acidosis. In those calves, determining the degree of loss of the palpebral reflex was identified as a useful decision criterion to provide an additional amount of 250 mmol sodium bicarbonate. This work demonstrates the clinical relevance of the discovery that D-lactate is responsible for most of the clinical signs expressed in neonatal diarrheic calves suffering from metabolic acidosis. PMID:23216654

Construction and validation of a decision tree for treating metabolic acidosis in calves with neonatal diarrhea.

PubMed

Trefz, Florian M; Lorch, Annette; Feist, Melanie; Sauter-Louis, Carola; Lorenz, Ingrid

2012-12-06

The aim of the present prospective study was to investigate whether a decision tree based on basic clinical signs could be used to determine the treatment of metabolic acidosis in calves successfully without expensive laboratory equipment. A total of 121 calves with a diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital were included in the study. The dosages of sodium bicarbonate administered followed simple guidelines based on the results of a previous retrospective analysis. Calves that were neither dehydrated nor assumed to be acidemic received an oral electrolyte solution. In cases in which intravenous correction of acidosis and/or dehydration was deemed necessary, the provided amount of sodium bicarbonate ranged from 250 to 750 mmol (depending on alterations in posture) and infusion volumes from 1 to 6.25 liters (depending on the degree of dehydration). Individual body weights of calves were disregarded. During the 24 hour study period the investigator was blinded to all laboratory findings. After being lifted, many calves were able to stand despite base excess levels below -20 mmol/l. Especially in those calves, metabolic acidosis was undercorrected with the provided amount of 500 mmol sodium bicarbonate, which was intended for calves standing insecurely. In 13 calves metabolic acidosis was not treated successfully as defined by an expected treatment failure or a measured base excess value below -5 mmol/l. By contrast, 24 hours after the initiation of therapy, a metabolic alkalosis was present in 55 calves (base excess levels above +5 mmol/l). However, the clinical status was not affected significantly by the metabolic alkalosis. Assuming re-evaluation of the calf after 24 hours, the tested decision tree can be recommended for the use in field practice with minor modifications. Calves that stand insecurely and are not able to correct their position if pushed require higher doses of sodium bicarbonate, if there is clinical evidence of a marked D-lactic acidosis. In those calves, determining the degree of loss of the palpebral reflex was identified as a useful decision criterion to provide an additional amount of 250 mmol sodium bicarbonate. This work demonstrates the clinical relevance of the discovery that D-lactate is responsible for most of the clinical signs expressed in neonatal diarrheic calves suffering from metabolic acidosis.

Genomewide association study of liver abscess in beef cattle.

PubMed

Keele, J W; Kuehn, L A; McDaneld, T G; Tait, R G; Jones, S A; Keel, B N; Snelling, W M

2016-02-01

Fourteen percent of U.S. cattle slaughtered in 2011 had liver abscesses, resulting in reduced carcass weight, quality, and value. Liver abscesses can result from a common bacterial cause, , which inhabits rumen lesions caused by acidosis and subsequently escapes into the blood stream, is filtered by the liver, and causes abscesses in the liver. Our aim was to identify SNP associated with liver abscesses in beef cattle. We used lung samples as a DNA source because they have low economic value, they have abundant DNA, and we had unrestricted access to sample them. We collected 2,304 lung samples from a beef processing plant: 1,152 from animals with liver abscess and 1,152 from animals without liver abscess. Lung tissue from pairs of animals, 1 with abscesses and another without, were collected from near one another on the viscera table to ensure that pairs of phenotypically extreme animals came from the same lot. Within each phenotype (abscess or no abscess), cattle were pooled by slaughter sequence into 12 pools of 96 cattle for each phenotype for a total of 24 pools. The pools were constructed by equal volume of frozen lung tissue from each animal. The DNA needed to allelotype each pool was then extracted from pooled lung tissue and the BovineHD Bead Array (777,962 SNP) was run on all 24 pools. Total intensity (TI), an indicator of copy number variants, was the sum of intensities from red and green dyes. Pooling allele frequency (PAF) was red dye intensity divided TI. Total intensity and PAF were weighted by the inverse of their respective genomic covariance matrices computed over all SNP across the genome. A false discovery rate ≤ 5% was achieved for 15 SNP for PAF and 20 SNP for TI. Genes within 50 kbp from significant SNP were in diverse pathways including maintenance of pH homeostasis in the gastrointestinal tract, maintain immune defenses in the liver, migration of leukocytes from the blood into infected tissues, transport of glutamine into the kidney in response to acidosis to facilitate production of bicarbonate to increase pH, aggregate platelets to liver injury to facilitate liver repair, and facilitate axon guidance. Evidence from the 35 detected SNP associations combined with evidence of polygenic variation indicate that there is adequate genetic variation in incidence rate of liver abscesses, which could be exploited to select sires for reduced susceptibility to subacute acidosis and associated liver abscess.

Incidence, prevalence, severity, and risk factors for ruminal acidosis in feedlot steers during backgrounding, diet transition, and finishing.

PubMed

Castillo-Lopez, E; Wiese, B I; Hendrick, S; McKinnon, J J; McAllister, T A; Beauchemin, K A; Penner, G B

2014-07-01

The objective of this study was to determine the incidence, prevalence, severity, and risk factors for ruminal acidosis in feedlot steers during backgrounding, diet transition, and finishing. Steers were purchased from a local auction market (n = 250; mean ± SD; 330 ± 20.0 kg initial BW) and were grouped together with 28 steers fitted with a ruminal cannula (248 ± 25.5 kg initial BW). Steers were randomly allocated to 1 of 8 pens (3 to 4 cannulated steers per pen with a total of 35 steers/pen). The feeding period (143 d) was divided into 4 phases: backgrounding (BKGD; d 1 to 20), diet transition (TRAN; d 21 to 40), and the first (FIN1; d 41 to 91) and second half (FIN2; d 92 to 143) of finishing. The BKGD diet contained (% DM) barley silage (45.7%), barley grain (41.6%), canola meal (4.2%), and a pelleted mineral and vitamin supplement (8.5%). Steers were transitioned to a finishing diet containing (% DM) barley silage (5%), barley grain (80.9%), canola meal (4.9%), and a pelleted mineral and vitamin supplement (9.2%) using 4 transition diets. Feed was offered to achieve 5% refusals (as-is basis). Ruminal pH was recorded in cannulated steers every 10 min throughout the study, and feed refusals and BW were recorded at 2 wk intervals. Mean ruminal pH (P < 0.01) was 6.4, 6.3, 6.2, and 6.0 ± 0.01 during the BKGD, TRAN, FIN1, and FIN2, respectively. The duration (P < 0.01) pH < 5.5 was 4.1, 12.1, 78.7, and 194 ± 9.4 min/d during BKGD, TRAN, FIN1, and FIN2, respectively. Using a threshold of ruminal pH < 5.5 for at least 180 min to diagnose ruminal acidosis, incidence was defined as the number of times steers experienced ruminal acidosis during each period and prevalence was defined as the percentage of steers that experienced acidosis during each period. On average, the incidence rate (P < 0.01) of ruminal acidosis was 0.1, 0.3, 6.7, and 14.8 ± 0.97 episodes during BKGD, TRAN, FIN1, and FIN2, respectively. In the same order, the prevalence (P < 0.01) was 0.7, 1.7, 15.4, and 37.8 ± 2.0%. Based on multiple regression, factors associated with prevalence of ruminal acidosis and the duration pH < 5.5 were feeding phase (P < 0.01) and DMI (P < 0.01). Overall, the greatest incidence, prevalence, and severity of ruminal acidosis were observed towards the end of the finishing phase and were associated with days on feed and DMI.

A Patient with Cystinosis Presenting Like Bartter Syndrome and Review of Literature

PubMed Central

Ertan, Pelin; Evrengul, Havva; Ozen, Serkan; Emre, Sinan

2012-01-01

Background Nephropathic cystinosis is an autosomal recessively inherited metabolic disorder presenting with metabolic acidosis, Fanconi syndrome and renal failure. Case Presentation We present a 6-year-old girl with severe growth failure, hyponatremia and hypokalemia. Her parents were 4th degree relatives. Two relatives were diagnosed as end stage renal failure. She also had persistant hypokalemic hypochloremic metabolic alkalosis. Her renal function was normal at presentation. She was thought to have Bartter syndrome with supporting findings of elevated levels of renin and aldosterone with normal blood pressure, and hyperplasia of juxtaglomerular apparatus. Her metabolic alkalosis did not resolve despite supportive treatment. At 6th month of follow-up proteinuria, glucosuria and deterioration of renal function developed. Diagnosis of cystinosis was made with slit lamp examination and leukocyte cystine levels. At 12th month of follow-up her metabolic alkalosis has converted to metabolic acidosis. Conclusion In children presenting with persistant metabolic alkalosis, with family history of renal failure, and parental consanguinity, cystinosis should always be kept in mind as this disease is an important cause of end stage renal failure which may have features mimmicking Bartter syndrome. PMID:23431081

[Secondary hyperoxaluria and nephrocalcinosis due to ethylene glycol poisoning].

PubMed

Monet, C; Richard, E; Missonnier, S; Rebouissoux, L; Llanas, B; Harambat, J

2013-08-01

We report the case of a 3-year-old boy admitted to the pediatric emergency department for ethylene glycol poisoning. During hospitalization, he presented dysuria associated with crystalluria. Blood tests showed metabolic acidosis with an elevated anion gap. A renal ultrasound performed a few weeks later revealed bilateral medullary hyperechogenicity. Urine microscopic analysis showed the presence of weddellite crystals. Secondary nephrocalcinosis due to ethylene glycol intoxication was diagnosed. Hyperhydration and crystallization inhibition by magnesium citrate were initiated. Despite this treatment, persistent weddellite crystals and nephrocalcinosis were seen more than 2years after the intoxication. Ethylene glycol is metabolized in the liver by successive oxidations leading to its final metabolite, oxalic acid. Therefore, metabolic acidosis with an elevated anion gap is usually found following ethylene glycol intoxication. Calcium oxalate crystal deposition may occur in several organs, including the kidneys. The precipitation of calcium oxalate in renal tubules can lead to nephrocalcinosis and acute kidney injury. The long-term renal prognosis is related to chronic tubulointerstitial injury caused by nephrocalcinosis. Treatment of ethylene glycol intoxication is based on specific inhibitors of alcohol dehydrogenase and hemodialysis in the most severe forms, and should be started promptly. Copyright © 2013. Published by Elsevier SAS.

Internist, anesthesiologist and surgeon use of ketogenic diet.

PubMed

Cenci, Lorenzo; Paoli, Antonio; Omar, Hesham R; Dalvi, Prachiti; Camporesi, Enrico M; Mangar, Devanand; Quartesan, Silvia; Fiorito, Alberto; Bosco, Gerardo

2018-03-01

Ketogenic diet is being increasingly utilized in recent decades because of its success as an effective tool for short and intermediate-term weight loss. Promoting physiological ketosis from a drastically low carbohydrate diet is the fundamental basis for this diet regime. Though debated, these diets have been demonstrated to be effective, at least in the short- to medium terms, to manage excess weight, hyperlipidemia, and other cardiovascular risk factors. We reviewed the cardiovascular, metabolic, anesthetic, and postsurgical profiles in the literature and summarized technical issues of anesthesia and surgery along with long-term changes from published papers. Doubts with ketogenic diet were raised due to possible renal damage caused by significant excretion of nitrogen found in animal models, the effects of acidosis, and the concerns of increasing triglycerides and cholesterol levels. Though current literature supports the efficacy of very low carbohydrate keto-diets their potential negative effects on renal function and acidosis are debated. An increase in nitrogen excretion during protein metabolism in the postoperative period could lead to renal damage. Research on the value of ketogenic diets is emerging because of its value in weight loss and in managing other pathologies.

Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) may respond to adjunctive ketogenic diet.

PubMed

Steriade, Claude; Andrade, Danielle M; Faghfoury, Hanna; Tarnopolsky, Mark A; Tai, Peter

2014-05-01

Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome can present management challenges. Refractory seizures and stroke-like episodes leading to disability are common. We analyzed the clinical, electrophysiologic, and radiologic data of a 22-year-old woman with multiple episodes of generalized and focal status epilepticus and migratory cortical stroke-like lesions who underwent muscle biopsy for mitochondrial genome sequencing. Although initial mitochondrial genetic testing was negative, muscle biopsy demonstrated a mitochondrial DNA disease-causing mutation (m.3260A > G). New antiepileptic medications were added with each episode of focal status epilepticus with only temporary improvement, until a modified ketogenic diet and magnesium were introduced, leading to seizure freedom despite development of a new stroke-like lesion, and subsequent decrease in frequency of stroke-like episodes. We propose a metabolic model in which the ketogenic diet may lead to improvement of the function of respiratory chain complexes. The ketogenic diet may lead to improvement of mitochondrial dysfunction in MELAS, which in turn may promote better seizure control and less frequent stroke-like episodes. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

[An unexpected stage of alkalosis in the dynamics of the early posthemorrhagic period].

PubMed

Beliaev, A V

2000-01-01

A study was made on acid-base metabolism in early posthemorrhagic period as exemplified by examination of patients presenting with gastrointestinal hemorrhage. It has been ascertained that hemorrhage is accompanied by a mixed variant of the acid-base state (ABS) deviation, namely metabolic lactate-acidosis and respiratory alkalosis. In the time-related course of posthemorrhagic period such deviations persist in patients with lethal outcome; with the disease running a favourable course the above deviations are found to return to normal quite soon. The development of complications leads to staging in ABC, its stages being as follows: stage I--the initial stage, stage II--persisting metabolic acidosis and respiratory alkalosis, stage III--alkalosis, stage IV--normalization, with stage III of ABS being encouraged by hypocapnia caused by function disorders of the lungs in early posthemorrhagic period, normalization of cell metabolism, increase in the rate of urination as a reflection of the third earlier identified stage of water metabolism, with the H+ excretion in the urine at the previous level. The identified ABS stage III threatens coming trouble, being accompanied by metabolic deviations together with a risk of function disorder of the myocardium.

Liquid chromatographic–mass spectrometric method for simultaneous determination of small organic acids potentially contributing to acidosis in severe malaria☆

PubMed Central

Sriboonvorakul, Natthida; Leepipatpiboon, Natchanun; Dondorp, Arjen M.; Pouplin, Thomas; White, Nicholas J.; Tarning, Joel; Lindegardh, Niklas

2013-01-01

Acidosis is an important cause of mortality in severe falciparum malaria. Lactic acid is a major contributor to metabolic acidosis, but accounts for only one-quarter of the strong anion gap. Other unidentified organic acids have an independent strong prognostic significance for a fatal outcome. In this study, a simultaneous bio-analytical method for qualitative and quantitative assessment in plasma and urine of eight small organic acids potentially contributing to acidosis in severe malaria was developed and validated. High-throughput strong anion exchange solid-phase extraction in a 96-well plate format was used for sample preparation. Hydrophilic interaction liquid chromatography (HILIC) coupled to negative mass spectroscopy was utilized for separation and detection. Eight possible small organic acids; l-lactic acid (LA), α-hydroxybutyric acid (aHBA), β-hydroxybutyric acid (bHBA), p-hydroxyphenyllactic acid (pHPLA), malonic acid (MA), methylmalonic acid (MMA), ethylmalonic acid (EMA) and α-ketoglutaric acid (aKGA) were analyzed simultaneously using a ZIC-HILIC column with an isocratic elution containing acetonitrile and ammonium acetate buffer. This method was validated according to U.S. Food and Drug Administration guidelines with additional validation procedures for endogenous substances. Accuracy for all eight acids ranged from 93.1% to 104.0%, and the within-day and between-day precisions (i.e. relative standard deviations) were lower than 5.5% at all tested concentrations. The calibration ranges were: 2.5–2500 μg/mL for LA, 0.125–125 μg/mL for aHBA, 7.5–375 μg/mL for bHBA, 0.1–100 μg/mL for pHPLA, 1–1000 μg/mL for MA, 0.25–250 μg/mL for MMA, 0.25–100 μg/mL for EMA, and 30–1500 μg/mL for aKGA. Clinical applicability was demonstrated by analyzing plasma and urine samples from five patients with severe falciparum malaria; five acids had increased concentrations in plasma (range LA = 177–1169 μg/mL, aHBA = 4.70–38.4 μg/mL, bHBA = 7.70–38.0 μg/mL, pHPLA = 0.900–4.30 μg/mL and aKGA = 30.2–32.0) and seven in urine samples (range LA = 11.2–513 μg/mL, aHBA = 1.50–69.5 μg/mL, bHBA = 8.10–111 μg/mL, pHPLA = 4.30–27.7 μg/mL, MMA = 0.300–13.3 μg/mL, EMA = 0.300–48.1 μg/mL and aKGA = 30.4–107 μg/mL). In conclusion, a novel bioanalytical method was developed and validated which allows for simultaneous quantification of eight small organic acids in plasma and urine. This new method may be a useful tool for the assessment of acidosis in patients with severe malaria, and other conditions complicated by acidosis. PMID:24200840

[A regenerative anemia in infants: 2 cases of Pearson´s syndrome].

PubMed

Martínez de Zabarte Fernández, José M; Rodríguez-Vigil Iturrate, Carmen; Martínez Faci, Cristina; García Jiménez, Inmaculada; Murillo Sanjuan, Laura; Muñoz Mellado, Ascensión

2017-02-01

Anemia is very common in infants. Although its causes are usually not severe and treatable, proper etiologic diagnosis should be established. When anemia is non-regenerative, it can be caused by aplastic anemia, myelodysplastic syndrome, bone marrow infiltration or hematopoietic factors deficiencies. Another possible cause is Pearson's syndrome, a rare mitochondrial disease that causes non-regenerative anemia associated with other cytopenias, pancreatic insufficiency, lactic acidosis and great variability in clinical presentation conditioned by heteroplasmy. It is characteristic to find in bone marrow studies variable vacuolization in erythroblastic progenitors and ring sideroblasts. The diagnosis is established by genetic study of mitochondrial deoxyribonucleic acid performed by Southern blot analysis (complete mitochondrial deoxyribonucleic acid amplification by polymerase chain reaction -long), obtaining 70-80% deletion of 4977 bp (NMD 8343-13459). There is no curative therapy and support treatment is the only available nowadays. Death is frequent in early years of life. Sociedad Argentina de Pediatría.

Acute Electrocardiographic ST Segment Elevation May Predict Hypotension in a Swine Model of Severe Cyanide Toxicity

DTIC Science & Technology

2012-04-21

model with severe acidosis (pH 6.8), hyperkalemia (up to 10 meq/L), hypoglycemia, and hypoxia and reported that ECG electrical changes were not directly...hypoxia, hyperkalemia , and acidosis on intracellular and extracellular poten tials and metabolism in the isolated porcine heart. Circ Res 46 (5):634

Assessment of nitric oxide production in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome with the use of a stable isotope tracer infusion technique

USDA-ARS?s Scientific Manuscript database

Mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient energy to meet the needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial...

Synergism of isothermal regimen and sodium succinate in experimental therapy of barbiturate coma.

PubMed

Reinyuk, V L; Shefer, T V; Ivnitskii, Yu Yu

2006-07-01

In rats with experimental thiopental coma rectal temperature decreased by 9.4 degrees C, oxygen consumption 5-fold, and arteriovenous Po(2)gradient decreased 2-fold within 3 h; CO(2)accumulated in the blood and mixed type acidosis developed. Administration of sodium succinate under these conditions increased arteriovenous Po(2)gradient and reduced manifestations of metabolic acidosis. Maintenance of normal body temperature (warming) corrected primarily manifestations of respiratory acidosis. Each therapeutic agent reduced inhibition of O(2)consumption by 1/4; animal survival tended to increase from 42 to 50%. Combined use of these treatments potentiated the antiacidotic effect and increased survival to 92%. The authors conclude that hypothermia inhibits the therapeutic effect of succinate in barbiturate coma.

A case of atypical thyroid storm with hypoglycemia and lactic acidosis.

PubMed

Izumi, Kenichi; Kondo, Shiori; Okada, Takanori

2009-01-01

We describe herein a case of thyroid storm with hypoglycemia and lactic acidosis-a rare complication of thyroid storm. The patient was a 50-year-old Japanese woman who suffered cardiopulmonary arrest an hour after hospitalization. Analysis of a blood sample obtained before her cardiopulmonary arrest yielded surprising results: Her plasma glucose level was 14 mg/dL and her lactic acid concentration had increased to 6.238 mM. Thus, if atypical thyroid storm presents with normothermic hypoglycemia, and lactic acidosis, we believe it is necessary to consider a diagnosis of thyroid storm earlier, because this condition requires emergency treatment. Moreover, it is very important to apply standard principles in the treatment of atypical cases of thyroid storm.

Can phenformin-induced lactic acidosis be prevented?

PubMed Central

Gale, E A; Tattersall, R B

1976-01-01

Although patients taking phenformin are more likely to develop lactic acidosis in the presence of renal, cardiovascular, or hepatic disease, criteria for safe use of the drug are not well established. Eight diabetics died of lactic acidosis in Nottingham in 1972-5 and all were taking phenformin in therapeutic doses. Six had attended the diabetic clinic within a month of their terminal illness. Two patients had appreciable renal impairment and should not have been given phenformin. Four had hypertension and minimal evidence of renal disease, while in two no predisposing factor was identified. There are so many contraindications to the use of phenformin that it is doubtful whether patients on the drug can be monitored adequately. We suggest that phenformin should be withdrawn from general use. PMID:974710

Nitrogen metabolism, acid-base regulation, and molecular responses to ammonia and acid infusions in the spiny dogfish shark (Squalus acanthias).

PubMed

Nawata, C Michele; Walsh, Patrick J; Wood, Chris M

2015-07-01

Although they are ureotelic, marine elasmobranchs express Rh glycoproteins, putative ammonia channels. To address questions raised by a recent study on high environmental ammonia (HEA) exposure, dogfish were intravascularly infused for 24 h at 3 ml kg(-1) h(-1) with isosmotic NaCl (500 mmol l(-1), control), NH4HCO3 (500 mmol l(-1)), NH4Cl (500 mmol l(-1)), or HCl (as 125 mmol l(-1) HCl + 375 mmol l(-1) NaCl). While NaCl had no effect on arterial acid-base status, NH4HCO3 caused mild alkalosis, NH4Cl caused strong acidosis, and HCl caused lesser acidosis, all predominantly metabolic in nature. Total plasma ammonia (T(Amm)) and excretion rates of ammonia (J(Amm)) and urea-N (J(Urea-N)) were unaffected by NaCl or HCl. However, despite equal loading rates, plasma T(Amm) increased to a greater extent with NH4Cl, while J(Amm) increased to a greater extent with NH4HCO3 due to much greater increases in blood-to-water PNH3 gradients. As with HEA, both treatments caused large (90%) elevations of J(Urea-N), indicating that urea-N synthesis by the ornithine-urea cycle (OUC) is driven primarily by ammonia rather than HCO3(-). Branchial mRNA expressions of Rhbg and Rhp2 were unaffected by NH4HCO3 or NH4Cl, but v-type H(+)-ATPase was down-regulated by both treatments, and Rhbg and Na(+)/H(+) exchanger NHE2 were up-regulated by HCl. In the kidney, Rhbg was unresponsive to all treatments, but Rhp2 was up-regulated by HCl, and the urea transporter UT was up-regulated by HCl and NH4Cl. These responses are discussed in the context of current ideas about branchial, renal, and OUC function in this nitrogen-limited predator.

Swimming Three Ice Miles within Fifteen Hours.

PubMed

Stjepanovic, Mirko; Nikolaidis, Pantelis T.; Knechtle, Beat

2017-08-31

Ice Mile swimming (1608 m in water of below 5 °Celsius) is becoming increasingly popular. This case study aimed to identify body core temperature and selected haematological and biochemical parameters before and after repeated Ice Miles. An experienced ice swimmer completed three consecutive Ice Miles within 15 h. Swim times, body core temperatures, and selected urinary and haematological parameters were recorded. Body core temperature reached its maximum between 5, 8 and 15 min after immersion (37.7°C, 38.1°C, and 38.0°C, respectively). The swimmer suffered hypothermia during the first Ice Mile (35.4°C) and body core temperature dropped furthermore to 34.5°C during recovery after the first Ice Mile. He developed a metabolic acidosis in both the first and the last Ice Mile (pH 7.31 and pH 7.34, respectively). We observed hyperkalaemia ([K⁺] > 5.5 mM) after the second Ice Mile (6.9 mM). This was followed by a drop in [K⁺] to3.7 mM after the third Ice Mile. Anticipatory thermogenesis (i.e. an initial increase of body core temperature after immersion in ice cold water) seems to be a physiological response in a trained athlete. The results suggest that swimming in ice-cold water leads to a metabolic acidosis, which the swimmer compensates with hyperventilation (i.e. leading to respiratory alkalosis). The shift of serum [K⁺] could increase the risk of a cardiac arrhythmia. Further studies addressing the physiology and potential risks of Ice Mile swimming are required to substantiate this finding.

dRTA and hemolytic anemia: first detailed description of SLC4A1 A858D mutation in homozygous state.

PubMed

Fawaz, Naglaa A; Beshlawi, Ismail O; Al Zadjali, Shoaib; Al Ghaithi, Hamed K; Elnaggari, Mohamed A; Elnour, Ibtisam; Wali, Yasser A; Al-Said, Bushra B; Rehman, Jalil U; Pathare, Anil V; Knox-Macaulay, Huxley; Alkindi, Salam S

2012-04-01

Mutations in the anion exchanger 1 (AE1) gene encoding the erythroid and kidney anion (chloride-bicarbonate) exchanger 1 may result in familial distal renal tubular acidosis (dRTA) in association with membrane defect hemolytic anemia. Seven children presenting with hyperchloremic normal anion gap metabolic acidosis, failure to thrive, and compensated hemolytic anemia were studied. Analysis of red cell AE1/Band 3 surface expression by Eosin 5'-maleimide (E5M) was performed in patients and their family members using flow cytometry. Genetic studies showed that all patients carried a common SLC4A1 mutation, c.2573C>A; p.Ala858Asp in exon 19, found as homozygous (A858D/A858D) mutation in the patients and heterozygous (A858D/N) in the parents. Analysis by flowcytometry revealed a single uniform fluorescence peak, with the mean channel fluorescence (MCF) markedly reduced in cases with homozygous mutation, along with a left shift of fluorescence signal but was only mildly reduced in the heterozygous state. Red cell morphology showed striking acanthocytosis in the homozygous state [patients] and only a mild acanthocytosis in heterozygous state [parents]. In conclusion, this is the first description of a series of homozygous cases with the A858D mutation. The E5M flowcytometry test is specific for reduction in the Band 3 membrane protein and was useful in conjunction with a careful morphological examination of peripheral blood smears in our patient cohort. © 2012 John Wiley & Sons A/S.

Invasive aspergillosis in a patient with MELAS syndrome

PubMed Central

McKee, D; Cooper, P; Denning, D

2000-01-01

Invasive infection with the opportunistic fungus Aspergillus fumigatus predominantly affects people with impaired cell mediated immunity. The case of a 31 year old woman with no identified cause for immunosuppression who presented with severe refractory aspergillosis of the paranasal sinuses is reported. She subsequently developed clinical and molecular evidence of mitochondrial encephalomyopathy with lactic acidosis and stroke-like events (MELAS) syndrome. It is proposed that MELAS syndrome may represent an unusual risk factor for the development of invasive aspergillosis and mechanisms are supported by which mitochondrial dysfunction may predispose to this.

 PMID:10811702

Toxigenic and metabolic causes of ketosis and ketoacidotic syndromes.

PubMed

Cartwright, Martina M; Hajja, Waddah; Al-Khatib, Sofian; Hazeghazam, Maryam; Sreedhar, Dharmashree; Li, Rebecca Na; Wong-McKinstry, Edna; Carlson, Richard W

2012-10-01

Ketoacidotic syndromes are frequently encountered in acute care medicine. This article focuses on ketosis and ketoacidotic syndromes associated with intoxications, alcohol abuse, starvation, and certain dietary supplements as well as inborn errors of metabolism. Although all of these various processes are characterized by the accumulation of ketone bodies and metabolic acidosis, there are differences in the mechanisms, clinical presentations, and principles of therapy for these heterogeneous disorders. Pathophysiologic mechanisms that account for these disorders are presented, as well as guidance regarding identification and management. Copyright © 2012 Elsevier Inc. All rights reserved.

The use of elements of the Stewart model (Strong Ion Approach) for the diagnostics of respiratory acidosis on the basis of the calculation of a value of a modified anion gap (AGm) in brachycephalic dogs.

PubMed

Sławuta, P; Glińska-Suchocka, K; Cekiera, A

2015-01-01

Apart from the HH equation, the acid-base balance of an organism is also described by the Stewart model, which assumes that the proper insight into the ABB of the organism is given by an analysis of: pCO2, the difference of concentrations of strong cations and anions in the blood serum - SID, and the total concentration of nonvolatile weak acids - Acid total. The notion of an anion gap (AG), or the apparent lack of ions, is closely related to the acid-base balance described according to the HH equation. Its value mainly consists of negatively charged proteins, phosphates, and sulphates in blood. In the human medicine, a modified anion gap is used, which, including the concentration of the protein buffer of blood, is, in fact, the combination of the apparent lack of ions derived from the classic model and the Stewart model. In brachycephalic dogs, respiratory acidosis often occurs, which is caused by an overgrowth of the soft palate, making it impossible for a free air flow and causing an increase in pCO2--carbonic acid anhydride The aim of the present paper was an attempt to answer the question whether, in the case of systemic respiratory acidosis, changes in the concentration of buffering ions can also be seen. The study was carried out on 60 adult dogs of boxer breed in which, on the basis of the results of endoscopic examination, a strong overgrowth of the soft palate requiring a surgical correction was found. For each dog, the value of the anion gap before and after the palate correction procedure was calculated according to the following equation: AG = ([Na+ mmol/l] + [K+ mmol/l])--([Cl- mmol/l]+ [HCO3- mmol/l]) as well as the value of the modified AG--according to the following equation: AGm = calculated AG + 2.5 x (albumins(r)--albumins(d)). The values of AG calculated for the dogs before and after the procedure fell within the limits of the reference values and did not differ significantly whereas the values of AGm calculated for the dogs before and after the procedure differed from each other significantly. 1) On the basis of the values of AGm obtained it should be stated that in spite of finding respiratory acidosis in the examined dogs, changes in ion concentration can also be seen, which, according to the Stewart theory, compensate metabolic ABB disorders 2) In spite of the fact that all the values used for calculation of AGm were within the limits of reference values, the values of AGm in dogs before and after the soft palate correction procedure differed from each other significantly, which proves high sensitivity and usefulness of the AGm calculation as a diagnostic method.

Metabolic acidosis stimulates the production of the antimicrobial peptide cathelicidin in rabbit urine.

PubMed

Peng, Hu; Purkerson, Jeffrey M; Schwaderer, Andy L; Schwartz, George J

2017-11-01

Intercalated cells of the collecting duct (CD) are critical for acid-base homeostasis and innate immune defense of the kidney. Little is known about the impact of acidosis on innate immune defense in the distal nephron. Urinary tract infections are mainly due to Escherichia coli and are an important risk factor for development of chronic kidney disease. While the effect of urinary pH on growth of E. coli is well established, in this study, we demonstrate that acidosis increases urine antimicrobial activity due, at least in part, to induction of cathelicidin expression within the CD. Acidosis was induced in rabbits by adding NH 4 Cl to the drinking water and reducing food intake over 3 days or by casein supplementation. Microdissected CDs were examined for cathelicidin mRNA expression and antimicrobial activity, and cathelicidin protein levels in rabbit urine were measured. Cathelicidin expression in CD cells was detected in kidney sections. CDs from acidotic rabbits expressed three times more cathelicidin mRNA than those isolated from normal rabbits. Urine from acidotic rabbits had significantly more antimicrobial activity (vs. E. coli ) than normal urine, and most of this increased activity was blocked by cathelicidin antibody. The antibody had little effect on antimicrobial activity of normal urine. Urine from acidotic rabbits had at least twice the amount of cathelicidin protein as did normal urine. We conclude that metabolic acidosis not only stimulates CD acid secretion but also induces expression of cathelicidin and, thereby, enhances innate immune defense against urinary tract infections via induction of antimicrobial peptide expression. Copyright © 2017 the American Physiological Society.

Chloride Content of Fluids Used for Large-Volume Resuscitation Is Associated With Reduced Survival.

PubMed

Sen, Ayan; Keener, Christopher M; Sileanu, Florentina E; Foldes, Emily; Clermont, Gilles; Murugan, Raghavan; Kellum, John A

2017-02-01

We sought to investigate if the chloride content of fluids used in resuscitation was associated with short- and long-term outcomes. We identified patients who received large-volume fluid resuscitation, defined as greater than 60 mL/kg over a 24-hour period. Chloride load was determined for each patient based on the chloride ion concentration of the fluids they received during large-volume fluid resuscitation multiplied by the volume of fluids. We compared the development of hyperchloremic acidosis, acute kidney injury, and survival among those with higher and lower chloride loads. University Medical Center. Patients admitted to ICUs from 2000 to 2008. None. Among 4,710 patients receiving large-volume fluid resuscitation, hyperchloremic acidosis was documented in 523 (11%). Crude rates of hyperchloremic acidosis, acute kidney injury, and hospital mortality all increased significantly as chloride load increased (p < 0.001). However, chloride load was no longer associated with hyperchloremic acidosis or acute kidney injury after controlling for total fluids, age, and baseline severity. Conversely, each 100 mEq increase in chloride load was associated with a 5.5% increase in the hazard of death even after controlling for total fluid volume, age, and severity (p = 0.0015) over 1 year. Chloride load is associated with significant adverse effects on survival out to 1 year even after controlling for total fluid load, age, and baseline severity of illness. However, the relationship between chloride load and development of hyperchloremic acidosis or acute kidney injury is less clear, and further research is needed to elucidate the mechanisms underlying the adverse effects of chloride load on survival.

Acidosis and weight loss are induced by cyclosporin A in uninephrectomized rats.

PubMed

Jaramillo-Juárez, F; Rodríguez-Vázquez, M L; Namorado, M C; Martín, D; Reyes, J L

2000-02-01

The effects of cyclosporin A (CyA, 50 mg/kg body weight) or its commercial vehicle (cremophor) on the acid-base regulation of uninephrectomized rats were assessed for 7 days and in non-nephrectomized rats for 15 days. CyA induced a marked systemic acidosis, accompanied by decreases in blood PCO(2) and plasma bicarbonate. Untreated uninephrectomized rats did not show the acidosis. In CyA-treated rats the urine pH decreased (control 6. 65+/-0.06 vs. CyA 6.18+/-0.08; P<0.01) as well as urinary bicarbonate (non-nephrectomized rats 7.50+/-1.88 mM vs. uninephrectomy plus CyA 0.75+/- 0.06 mM; P<0.01), suggesting partial renal compensation of systemic acidosis. Titratable acidity increased in CyA-treated rats (control 21.6+/-1.2 vs. CyA 63.3+/-12.0 microEq/l; P<0.001). Phosphate, glucose, and osmolar clearances were not significantly altered in non-nephrectomized rats treated with CyA for 15 days. There was a striking decrease in body weight in CyA-treated rats (control 274.0+/-3.8 vs. CyA 225.0+/-5.1 g; P<0. 01), but compensatory growth of the remaining kidney was not prevented by this drug or by its vehicle. In summary, CyA induced a severe metabolic acidosis in uninephrectomized rats that was not compensated by the remaining kidney, in spite of the well-preserved compensatory weight gain of this organ. Loss of body weight was significant in CyA-treated animals.

Oxygen consumption is depressed in patients with lactic acidosis due to biguanide intoxication.

PubMed

Protti, Alessandro; Russo, Riccarda; Tagliabue, Paola; Vecchio, Sarah; Singer, Mervyn; Rudiger, Alain; Foti, Giuseppe; Rossi, Anna; Mistraletti, Giovanni; Gattinoni, Luciano

2010-01-01

Lactic acidosis can develop during biguanide (metformin and phenformin) intoxication, possibly as a consequence of mitochondrial dysfunction. To verify this hypothesis, we investigated whether body oxygen consumption (VO2), that primarily depends on mitochondrial respiration, is depressed in patients with biguanide intoxication. Multicentre retrospective analysis of data collected from 24 patients with lactic acidosis (pH 6.93 +/- 0.20; lactate 18 +/- 6 mM at hospital admission) due to metformin (n = 23) or phenformin (n = 1) intoxication. In 11 patients, VO2 was computed as the product of simultaneously recorded arterio-venous difference in O2 content [C(a-v)O2] and cardiac index (CI). In 13 additional cases, C(a-v)O2, but not CI, was available. On day 1, VO2 was markedly depressed (67 +/- 28 ml/min/m2) despite a normal CI (3.4 +/- 1.2 L/min/m2). C(a-v)O2 was abnormally low in both patients either with (2.0 +/- 1.0 ml O2/100 ml) or without (2.5 +/- 1.1 ml O2/100 ml) CI (and VO2) monitoring. Clearance of the accumulated drug was associated with the resolution of lactic acidosis and a parallel increase in VO2 (P < 0.001) and C(a-v)O2 (P < 0.05). Plasma lactate and VO2 were inversely correlated (R2 0.43; P < 0.001, n = 32). VO2 is abnormally low in patients with lactic acidosis due to biguanide intoxication. This finding is in line with the hypothesis of inhibited mitochondrial respiration and consequent hyperlactatemia.

Polyuria, acidosis, and coma following massive ibuprofen ingestion.

PubMed

Levine, Michael; Khurana, Amandeep; Ruha, Anne-Michelle

2010-09-01

Ibuprofen was the first over-the-counter nonsteroidal anti-inflammatory drug available in the United States. Despite being a common agent of ingestion, significant toxicity in overdose is rare. We report a case of a massive ibuprofen ingestion who developed polyuria, acidosis, and coma but survived, despite having a serum ibuprofen concentration greater than previous fatal cases. A 19-year-old man ingested 90 g (1,200 mg/kg) ibuprofen. He was initially awake and alert, but his level of consciousness deteriorated over several hours. Seven hours following the ingestion, he was intubated and mechanically ventilated secondary to loss of airway reflexes. He developed a lactic acidosis and polyuria, which lasted for nearly 24 h. His serum creatinine peaked at 1.12 mg/dL. An ibuprofen level drawn 7 h postingestion was 739.2 mg/L (therapeutic 5-49 mg/L). We describe a case of a massive ibuprofen overdose characterized by metabolic acidosis, coma, and a state of high urine output who survived with aggressive supportive care. This case is unique in several ways. First, ibuprofen levels this high have only rarely been described. Second, polyuria is very poorly described following ibuprofen ingestions.

Coenzyme Q 10 improves lactic acidosis, strokelike episodes, and epilepsy in a patient with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes).

PubMed

Berbel-Garcia, Angel; Barbera-Farre, Jose Ramon; Etessam, Jesús Porta; Salio, Antonio Martínez; Cabello, Ana; Gutierrez-Rivas, Eduardo; Campos, Yolanda

2004-01-01

Mitochondrial encephalomyopathies encompass a group of disorders that have impaired oxidative metabolism in skeletal muscles and central nervous system. Many compounds have been used in clinical trials on mitochondrial diseases, but the outcomes have been variable. It remains controversial whether treatment of mitochondrial diseases with coenzyme Q 10 is effective. This paper describes a case of mitochondrial myopathy, encephalopathy, lactic acidosis, strokelike episodes, and exercise intolerance successfully treated with coenzyme Q 10. Efficacy of this therapy in this patient is correlated to control of lactic acidosis and serum creatine kinase levels. Disappointingly, larger studies with coenzyme Q 10 failed to demonstrate a clear beneficial effect on the entire study population with regard to clinical improvement or several parameters of the oxidative metabolism. They suggest that the use of coenzyme Q in treatment of mitochondrial diseases should be confined to protocols. There is a confounding variation in phenotype and genotype, and the natural history of the disorders in individual patients is not accurately predictable. The unpredictable a priori efficacy of therapy suggests that a long-term trial of oral coenzyme Q may be warranted.

Elevated thyroid peroxidase antibodies with encephalopathy in MELAS syndrome.

PubMed

Chan, Derrick W S; Lim, C C Tchoyoson; Tay, Stacey K H; Choong, Chew-Thye; Phuah, Huan Kee

2007-06-01

Both the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) and Hashimoto's encephalopathy can present with nonspecific encephalopathy. Hashimoto's encephalopathy is an association of steroid-responsive encephalopathy with elevated thyroid peroxidase antibodies. Steroid-responsive encephalopathy, however, is not characteristic of the MELAS syndrome, which typically presents with stroke-like episodes and lactic acidosis in cerebrospinal fluid and blood. Here, a patient is described with goiter, recurrent encephalopathy and elevated thyroid peroxidase antibodies who apparently responded to steroid therapy; however, magnetic resonance imaging was atypical for Hashimoto's encephalopathy, and she was diagnosed with MELAS syndrome. This syndrome can present with apparent steroid-responsive encephalopathy and elevated thyroid peroxidase antibodies, mimicking Hashimoto's encephalopathy, and should be suspected if lactic acidosis is present and typical features are detected on magnetic resonance imaging.

Association of Metformin Use With Risk of Lactic Acidosis Across the Range of Kidney Function: A Community-Based Cohort Study.

PubMed

Lazarus, Benjamin; Wu, Aozhou; Shin, Jung-Im; Sang, Yingying; Alexander, G Caleb; Secora, Alex; Inker, Lesley A; Coresh, Josef; Chang, Alex R; Grams, Morgan E

2018-06-04

Approximately 1 million patients in the United States with type 2 diabetes mellitus and mild-to-moderate kidney disease do not receive guideline-directed therapy with metformin. This may reflect uncertainty regarding the risk of acidosis in patients with chronic kidney disease. To quantify the association between metformin use and hospitalization with acidosis across the range of estimated glomerular filtration rate (eGFR), accounting for change in eGFR stage over time. Community-based cohort of 75 413 patients with diabetes in Geisinger Health System, with time-dependent assessment of eGFR stage from January 2004 until January 2017. Results were replicated in 67 578 new metformin users and 14 439 new sulfonylurea users from 2010 to 2015, sourced from 350 private US health systems. Metformin use. Hospitalization with acidosis (International Classification of Diseases, Ninth Revision, Clinical Modification code of 276.2). In the primary cohort (n = 75 413), mean (SD) patient age was 60.4 (15.5) years, and 51% (n = 38 480) of the participants were female. There were 2335 hospitalizations with acidosis over a median follow-up of 5.7 years (interquartile range, 2.5-9.9 years). Compared with alternative diabetes management, time-dependent metformin use was not associated with incident acidosis overall (adjusted hazard ratio [HR], 0.98; 95% CI, 0.89-1.08) or in patients with eGFR 45 to 59 mL/min/1.73 m2 (adjusted HR, 1.16; 95% CI, 0.95-1.41) and eGFR 30 to 44 mL/min/1.73 m2 (adjusted HR, 1.09; 95% CI, 0.83-1.44). On the other hand, metformin use was associated with an increased risk of acidosis at eGFR less than 30 mL/min/1.73 m2 (adjusted HR, 2.07; 95% CI, 1.33-3.22). Results were consistent when new metformin users were compared with new sulfonylurea users (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 0.77; 95% CI, 0.29-2.05), in a propensity-matched cohort (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 0.71; 95% CI, 0.45-1.12), when baseline insulin users were excluded (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 1.16; 95% CI, 0.87-1.57), and in the replication cohort (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 0.86; 95% CI, 0.37-2.01). In 2 real-world clinical settings, metformin use was associated with acidosis only at eGFR less than 30 mL/min/1.73 m2. Our results support cautious use of metformin in patients with type 2 diabetes and eGFR of at least 30 mL/min/1.73 m2.

HAART toxicity masquerading as a surgical abdomen

PubMed Central

Feghali, Anthony; Wang, Yi; Irizarry, Evelyn; Lueders, Meno

2015-01-01

Introduction Intussusception is a rare disease in adults and poses a challenge to identify and manage. In adults, surgical resection is the preferred treatment since half are due to malignancy. This case reveals an association between highly active antiretroviral therapy (HAART) and intussusception. Presentation of case A 44 year-old female with history of HIV on highly active antiretroviral therapy (HAART) presented with 3 month history of epigastric pain, nausea, emesis, weight loss, and lactic acidosis. CT of abdomen showed two small bowel intussusceptions and pericolic fat infiltration. A diagnosis of mitochondrial toxicity secondary to HAART medication was made. HAART medication was discontinued with resolution of symptoms. Further work-up to exclude a mechanical cause for her symptoms including colonoscopy, small bowel follow through, esophagogastroduodenoscopy, and repeat CT were performed. All established an absence of malignancy and intussusception. Discussion Mitochondrial toxicity (MT) is a well-known complication of HAART. A hallmark of MT is lactic acidosis which when untreated can be fatal. Although MT is known to cause gastrointestinal symptoms, intussusception has not been previously reported. In our patient with MT, prolonged usage of HAART medication resulted in severe gastrointestinal symptoms and intussusception mimicking a surgical abdomen. Laparotomy has been recommended on adult patients with intussusceptions because of the high likelihood of identifying a pathologic lesion. The doctrine of adult intussusception is to operate for concern of malignancy. Conclusion Surgeons, gastroenterologist and internist caring for patients on HAART therapy must be aware of the possibility of MT when evaluating HIV patients for possible surgical abdomen. PMID:26686487

Old and new approaches to the interpretation of acid-base metabolism, starting from historical data applied to diabetic acidosis.

PubMed

Mioni, Roberto; Marega, Alessandra; Lo Cicero, Marco; Montanaro, Domenico

2016-11-01

The approach to acid-base chemistry in medicine includes several methods. Currently, the two most popular procedures are derived from Stewart's studies and from the bicarbonate/BE-based classical formulation. Another method, unfortunately little known, follows the Kildeberg theory applied to acid-base titration. By using the data produced by Dana Atchley in 1933, regarding electrolytes and blood gas analysis applied to diabetes, we compared the three aforementioned methods, in order to highlight their strengths and their weaknesses. The results obtained, by reprocessing the data of Atchley, have shown that Kildeberg's approach, unlike the other two methods, is consistent, rational and complete for describing the organ-physiological behavior of the hydrogen ion turnover in human organism. In contrast, the data obtained using the Stewart approach and the bicarbonate-based classical formulation are misleading and fail to specify which organs or systems are involved in causing or maintaining the diabetic acidosis. Stewart's approach, despite being considered 'quantitative', does not propose in any way the concept of 'an amount of acid' and becomes even more confusing, because it is not clear how to distinguish between 'strong' and 'weak' ions. As for Stewart's approach, the classical method makes no distinction between hydrogen ions managed by the intermediate metabolism and hydroxyl ions handled by the kidney, but, at least, it is based on the concept of titration (base-excess) and indirectly defines the concept of 'an amount of acid'. In conclusion, only Kildeberg's approach offers a complete understanding of the causes and remedies against any type of acid-base disturbance.

Chloride: the queen of electrolytes?

PubMed

Berend, Kenrick; van Hulsteijn, Leonard Hendrik; Gans, Rijk O B

2012-04-01

Channelopathies, defined as diseases that are caused by mutations in genes encoding ion channels, are associated with a wide variety of symptoms and have been documented extensively over the past decade. In contrast, despite the important role of chloride in serum, textbooks in general do not allocate chapters exclusively on hypochloremia or hyperchloremia and information on chloride other than channelopathies is scattered in the literature. To systematically review the function of chloride in man, data for this review include searches of MEDLINE, PubMed, and references from relevant articles including the search terms "chloride," "HCl," "chloride channel" "acid-base," "acidosis," "alkalosis," "anion gap" "strong anion gap" "Stewart," "base excess" and "lactate." In addition, internal medicine, critical care, nephrology and gastroenterology textbooks were evaluated on topics pertaining the assessment and management of acid-base disorders, including reference lists from journals or textbooks. Chloride is, after sodium, the most abundant electrolyte in serum, with a key role in the regulation of body fluids, electrolyte balance, the preservation of electrical neutrality, acid-base status and it is an essential component for the assessment of many pathological conditions. When assessing serum electrolytes, abnormal chloride levels alone usually signify a more serious underlying metabolic disorder, such as metabolic acidosis or alkalosis. Chloride is an important component of diagnostic tests in a wide array of clinical situations. In these cases, chloride can be tested in sweat, serum, urine and feces. Abnormalities in chloride channel expression and function in many organs can cause a range of disorders. Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Does Bicarbonate Correct Coagulation Function Impaired by Acidosis in Swine?

DTIC Science & Technology

2006-07-01

requires sufficient fibrinogen available in the circulation . At any time, fibrinogen availabil- Fig. 4. Thrombin generation kinetics at baseline (T0... circulation can potentially impact physiologic function. As the precursor in the coagulation process, fibrinogen is primarily involved in maintaining...with different proteins. It is also possible that following acidosis insult, some of the albumin loss from the circulation was compensated for by

Evaluation of the Use of Capnography during the Transport of Critically Ill Mechanically Ventilated Patients.

DTIC Science & Technology

1992-12-15

DISCUSSION: Gervais et a13 demonstrated that respiratory alkalosis developed when ICU patients were manually ventilated, without 7 spirometric...developed a respiratory acidosis. Use of the non-invasive monitor, the capnograph prevented this adverse effect and resulted in inIproved patient safety...ventilation, all patients developed respiratory acidoses. Capnography uniformly prevented the development of respiratory acidosis during transport. We

Concentration-dependent effect of hypocalcaemia on mortality of patients with critical bleeding requiring massive transfusion: a cohort study.

PubMed

Ho, K M; Leonard, A D

2011-01-01

Mortality of patients with critical bleeding requiring massive transfusion is high. Although hypothermia, acidosis and coagulopathy have been well described as important determinants of mortality in patients with critical bleeding requiring massive transfusion, the risk factors and outcome associated with hypocalcaemia in these patients remain uncertain. This cohort study assessed the relationship between the lowest ionised calcium concentration during the 24-hour period of critical bleeding and the hospital mortality of 352 consecutive patients, while adjusting for diagnosis, acidosis, coagulation results, transfusion requirements and use of recombinant factor VIIa. Hypocalcaemia was common (mean concentrations 0.77 mmol/l, SD 0.19) and had a linear; concentration-dependent relationship with mortality (odds ratio [OR] 1.25 per 0.1 mmol/l decrement, 95% confidence interval [CI]: 1.04 to 1.52; P = 0.02). Hypocalcaemia accounted for 12.5% of the variability and was more important than the lowest fibrinogen concentrations (10.8%), acidosis (7.9%) and lowest platelet counts (7.7%) in predicting hospital mortality. The amount of fresh frozen plasma transfused (OR 1.09 per unit, 95% CI: 1.02 to 1.17; P = 0.02) and acidosis (OR 1.45 per 0.1 decrement, 95% CI: 1.19 to 1.72; P = 0.01) were associated with the occurrence of severe hypocalcaemia (< 0.8 mmol/l). In conclusion, ionised calcium concentrations had an inverse concentration-dependent relationship with mortality of patients with critical bleeding requiring massive transfusion. Both acidosis and the amount of fresh frozen plasma transfused were the main risk factors for severe hypocalcaemia. Further research is needed to determine whether preventing ionised hypocalcaemia can reduce mortality of patients with critical bleeding requiring massive transfusion.

Phosphate binders and metabolic acidosis in patients undergoing maintenance hemodialysis—sevelamer hydrochloride, calcium carbonate, and bixalomer.

PubMed

Sanai, Toru; Tada, Hideo; Ono, Takashi; Fukumitsu, Toma

2015-01-01

The serum bicarbonate (HCO3(-)) levels are decreased in chronic hemodialysis (HD) patients treated with sevelamer hydrochloride (SH). We assessed the effects of bixalomer on the chronic metabolic acidosis in these patients. We examined 12 of the 122 consecutive Japanese patients with end-stage renal disease on HD, who orally ingested a dose of SH (≥2250 mg), and an arterial blood gas analysis and biochemical analysis were performed before HD. Patients whose serum HCO3(-) levels were under 18 mmol/L were changed from SH to the same dose of bixalomer. A total of 12 patients were treated with a large amount of SH. Metabolic acidosis (a serum HCO3(-) level under 18 mmol/L) was found in eight patients. These patients were also treated with or without small dose of calcium carbonate (1.2 ± 1.1 g). The dose of SH was changed to that of bixalomer. After 1 month, the serum HCO3(-) levels increased from 16.3 ± 1.4 to 19.6 ± 1.7 mmol/L (P < 0.05). Metabolic acidosis was not observed in four patients (serum HCO3(-) level: 20.3 ± 0.7 mmol/L) likely because they were taking 3 g of calcium carbonate with SH. In the present study, the development of chronic metabolic acidosis was induced by HCl containing phosphate binders, such as SH, and partially ameliorated by calcium carbonate, then subsequently improved after changing the treatment to bixalomer. © 2014 Fukumitsu Hospital. Hemodialysis International published by Wiley Periodicals, Inc. on behalf of International Society for Hemodialysis.

Metformin associated lactic acidosis (MALA): clinical profiling and management.

PubMed

Moioli, Alessandra; Maresca, Barbara; Manzione, Andrea; Napoletano, Antonello Maria; Coclite, Daniela; Pirozzi, Nicola; Punzo, Giorgio; Menè, Paolo

2016-12-01

Metformin (MF) accumulation during acute kidney injury is associated with high anion gap lactic acidosis type B (MF-associated lactic acidosis, MALA), a serious medical condition leading to high mortality. Despite dose adjustment for renal failure, diabetic patients with chronic kidney disease (CKD) stage III-IV are at risk for rapid decline in renal function by whatever reason, so that MF toxicity might arise if the drug is not timely withdrawn. Sixteen consecutive patients were admitted to our Hospital's Emergency Department with clinical findings consistent with MALA. Fifteen had prior history of CKD, 60 % of them with GFR between 30 and 60 ml/min. Of these, 5 required mechanical ventilation and cardiovascular support; 3 promptly recovered renal function after rehydration, whereas 10 (62 %) required continuous veno-venous renal replacement treatment. SOFA and SAPS II scores were significantly related to the degree of lactic acidosis. In addition, lactate levels were relevant to therapeutic choices, since they were higher in dialyzed patients than in those on conservative treatment (11.92 mmol/l vs 5.7 mmol/l, p = 0.03). The overall death rate has been 31 %, with poorer prognosis for worse acidemia, as serum pH was significantly lower in non-survivors (pH 6.96 vs 7.16, p > 0.04). Our own data and a review of the literature suggest that aged, hemodynamically frail patients, with several comorbidities and CKD, are at greater risk of MALA, despite MF dosage adjustment. Moreover, renal replacement therapy rather than simple acidosis correction by administration of alkali seems the treatment of choice, based on eventual renal recovery and overall outcome.

Regulation of renal amino acid transporters during metabolic acidosis.

PubMed

Moret, Caroline; Dave, Mital H; Schulz, Nicole; Jiang, Jean X; Verrey, Francois; Wagner, Carsten A

2007-02-01

The kidney plays a major role in acid-base homeostasis by adapting the excretion of acid equivalents to dietary intake and metabolism. Urinary acid excretion is mediated by the secretion of protons and titratable acids, particularly ammonia. NH(3) is synthesized in proximal tubule cells from glutamine taken up via specific amino acid transporters. We tested whether kidney amino acid transporters are regulated in mice in which metabolic acidosis was induced with NH(4)Cl. Blood gas and urine analysis confirmed metabolic acidosis. Real-time RT-PCR was performed to quantify the mRNAs of 16 amino acid transporters. The mRNA of phosphoenolpyruvate carboxykinase (PEPCK) was quantified as positive control for the regulation and that of GAPDH, as internal standard. In acidosis, the mRNA of kidney system N amino acid transporter SNAT3 (SLC38A3/SN1) showed a strong induction similar to that of PEPCK, whereas all other tested mRNAs encoding glutamine or glutamate transporters were unchanged or reduced in abundance. At the protein level, Western blotting and immunohistochemistry demonstrated an increased abundance of SNAT3 and reduced expression of the basolateral cationic amino acid/neutral amino acid exchanger subunit y(+)-LAT1 (SLC7A7). SNAT3 was localized to the basolateral membrane of the late proximal tubule S3 segment in control animals, whereas its expression was extended to the earlier S2 segment of the proximal tubule during acidosis. Our results suggest that the selective regulation of SNAT3 and y(+)LAT1 expression may serve a major role in the renal adaptation to acid secretion and thus for systemic acid-base balance.

Mitochondrial aquaporin-8 in renal proximal tubule cells: evidence for a role in the response to metabolic acidosis.

PubMed

Molinas, Sara M; Trumper, Laura; Marinelli, Raúl A

2012-08-01

Mitochondrial ammonia synthesis in proximal tubules and its urinary excretion are key components of the renal response to maintain acid-base balance during metabolic acidosis. Since aquaporin-8 (AQP8) facilitates transport of ammonia and is localized in inner mitochondrial membrane (IMM) of renal proximal cells, we hypothesized that AQP8-facilitated mitochondrial ammonia transport in these cells plays a role in the response to acidosis. We evaluated whether mitochondrial AQP8 (mtAQP8) knockdown by RNA interference is able to impair ammonia excretion in the human renal proximal tubule cell line, HK-2. By RT-PCR and immunoblotting, we found that AQP8 is expressed in these cells and is localized in IMM. HK-2 cells were transfected with short-interfering RNA targeting human AQP8. After 48 h, the levels of mtAQP8 protein decreased by 53% (P < 0.05). mtAQP8 knockdown decreased the rate of ammonia released into culture medium in cells grown at pH 7.4 (-31%, P < 0.05) as well as in cells exposed to acid (-90%, P < 0.05). We also evaluated mtAQP8 protein expression in HK-2 cells exposed to acidic medium. After 48 h, upregulation of mtAQP8 (+74%, P < 0.05) was observed, together with higher ammonia excretion rate (+73%, P < 0.05). In vivo studies in NH(4)Cl-loaded rats showed that mtAQP8 protein expression was also upregulated after 7 days of acidosis in renal cortex (+51%, P < 0.05). These data suggest that mtAQP8 plays an important role in the adaptive response of proximal tubule to acidosis possibly facilitating mitochondrial ammonia transport.

Carbonic anhydrase IX inhibition affects viability of cancer cells adapted to extracellular acidosis.

PubMed

Andreucci, Elena; Peppicelli, Silvia; Carta, Fabrizio; Brisotto, Giulia; Biscontin, Eva; Ruzzolini, Jessica; Bianchini, Francesca; Biagioni, Alessio; Supuran, Claudiu T; Calorini, Lido

2017-12-01

Among the players of the adaptive response of cancer cells able to promote a resistant and aggressive phenotype, carbonic anhydrase IX (CAIX) recently has emerged as one of the most relevant drug targets. Indeed, CAIX targeting has received a lot of interest, and selective inhibitors are currently under clinical trials. Hypoxia has been identified as the master inductor of CAIX, but, to date, very few is known about the influence that another important characteristic of tumor microenvironment, i.e., extracellular acidosis, exerts on CAIX expression and activity. In the last decades, acidic microenvironment has been associated with aggressive tumor phenotype endowed with epithelial-to-mesenchymal transition (EMT) profile, high invasive and migratory ability, apoptosis, and drug resistance. We demonstrated that melanoma, breast, and colorectal cancer cells transiently and chronically exposed to acidified medium (pH 6.7 ± 0.1) showed a significantly increased CAIX expression compared to those grown in standard conditions (pH 7.4 ± 0.1). Moreover, we observed that the CAIX inhibitor FC16-670A (also named SLC-0111, which just successfully ended phase I clinical trials) not only prevents such increased expression under acidosis but also promotes apoptotic and necrotic programs only in acidified cancer cells. Thus, CAIX could represent a selective target of acidic cancer cells and FC16-670A inhibitor as a useful tool to affect this aggressive subpopulation characterized by conventional therapy escape. Cancer cells overexpress CAIX under transient and chronic extracellular acidosis. Acidosis-induced CAIX overexpression is NF-κB mediated and HIF-1α independent. FC16-670A prevents CAIX overexpression and induces acidified cancer cell death.

Changes in the rumen epimural bacterial diversity of beef cattle as affected by diet and induced ruminal acidosis.

PubMed

Petri, R M; Schwaiger, T; Penner, G B; Beauchemin, K A; Forster, R J; McKinnon, J J; McAllister, T A

2013-06-01

Little is known about the nature of the rumen epithelial adherent (epimural) microbiome in cattle fed different diets. Using denaturing gradient gel electrophoresis (DGGE), quantitative real-time PCR (qPCR), and pyrosequencing of the V3 hypervariable coding region of 16S rRNA, epimural bacterial communities of 8 cattle were profiled during the transition from a forage to a high-concentrate diet, during acidosis, and after recovery. A total of 153,621 high-quality gene sequences were obtained, with populations exhibiting less taxonomic variability among individuals than across diets. The bacterial community composition exhibited clustering (P < 0.03) by diet, with only 14 genera, representing >1% of the rumen epimural population, differing (P ≤ 0.05) among diets. During acidosis, levels of Atopobium, Desulfocurvus, Fervidicola, Lactobacillus, and Olsenella increased, while during the recovery, Desulfocurvus, Lactobacillus, and Olsenella reverted to levels similar to those with the high-grain diet and Sharpea and Succinivibrio reverted to levels similar to those with the forage diet. The relative abundances of bacterial populations changed during diet transition for all qPCR targets except Streptococcus spp. Less than 5% of total operational taxonomic units (OTUs) identified exhibited significant variability across diets. Based on DGGE, the community structures of epithelial populations differed (P ≤ 0.10); segregation was most prominent for the mixed forage diet versus the grain, acidotic challenge, and recovery diets. Atopobium, cc142, Lactobacillus, Olsenella, RC39, Sharpea, Solobacterium, Succiniclasticum, and Syntrophococcus were particularly prevalent during acidosis. Determining the metabolic roles of these key genera in the rumens of cattle fed high-grain diets could define a clinical microbial profile associated with ruminal acidosis.

Infusion of sodium bicarbonate in experimentally induced metabolic acidosis does not provoke cerebrospinal fluid (CSF) acidosis in calves.

PubMed

Abeysekara, Saman; Zello, Gordon A; Lohmann, Katharina L; Alcorn, Jane; Hamilton, Don L; Naylor, Jonathan M

2012-01-01

In a crossover study, 5 calves were made acidotic by intermittent intravenous infusion of isotonic hydrochloric acid (HCl) over approximately 24 h. This was followed by rapid (4 h) or slow (24 h) correction of blood pH with isotonic sodium bicarbonate (NaHCO(3)) to determine if rapid correction of acidemia produced paradoxical cerebrospinal fluid (CSF) acidosis. Infusion of HCl produced a marked metabolic acidosis with respiratory compensation. Venous blood pH (mean ± S(x)) was 7.362 ± 0.021 and 7.116 ± 0.032, partial pressure of carbon dioxide (Pco(2), torr) 48.8 ± 1.3 and 34.8 ± 1.4, and bicarbonate (mmol/L), 27.2 ± 1.27 and 11 ± 0.96; CSF pH was 7.344 ± 0.031 and 7.240 ± 0.039, Pco(2) 42.8 ± 2.9 and 34.5 ± 1.4, and bicarbonate 23.5 ± 0.91 and 14.2 ± 1.09 for the period before the infusion of hydrochloric acid and immediately before the start of sodium bicarbonate correction, respectively. In calves treated with rapid infusion of sodium bicarbonate, correction of venous acidemia was significantly more rapid and increases in Pco(2) and bicarbonate in CSF were also more rapid. However, there was no significant difference in CSF pH. After 4 h of correction, CSF pH was 7.238 ± 0.040 and 7.256 ± 0.050, Pco(2) 44.4 ± 2.2 and 34.2 ± 2.1, and bicarbonate 17.8 ± 1.02 and 14.6 ± 1.4 for rapid and slow correction, respectively. Under the conditions of this experiment, rapid correction of acidemia did not provoke paradoxical CSF acidosis.

Changes in the Rumen Epimural Bacterial Diversity of Beef Cattle as Affected by Diet and Induced Ruminal Acidosis

PubMed Central

Petri, R. M.; Schwaiger, T.; Penner, G. B.; Beauchemin, K. A.; Forster, R. J.; McKinnon, J. J.

2013-01-01

Little is known about the nature of the rumen epithelial adherent (epimural) microbiome in cattle fed different diets. Using denaturing gradient gel electrophoresis (DGGE), quantitative real-time PCR (qPCR), and pyrosequencing of the V3 hypervariable coding region of 16S rRNA, epimural bacterial communities of 8 cattle were profiled during the transition from a forage to a high-concentrate diet, during acidosis, and after recovery. A total of 153,621 high-quality gene sequences were obtained, with populations exhibiting less taxonomic variability among individuals than across diets. The bacterial community composition exhibited clustering (P < 0.03) by diet, with only 14 genera, representing >1% of the rumen epimural population, differing (P ≤ 0.05) among diets. During acidosis, levels of Atopobium, Desulfocurvus, Fervidicola, Lactobacillus, and Olsenella increased, while during the recovery, Desulfocurvus, Lactobacillus, and Olsenella reverted to levels similar to those with the high-grain diet and Sharpea and Succinivibrio reverted to levels similar to those with the forage diet. The relative abundances of bacterial populations changed during diet transition for all qPCR targets except Streptococcus spp. Less than 5% of total operational taxonomic units (OTUs) identified exhibited significant variability across diets. Based on DGGE, the community structures of epithelial populations differed (P ≤ 0.10); segregation was most prominent for the mixed forage diet versus the grain, acidotic challenge, and recovery diets. Atopobium, cc142, Lactobacillus, Olsenella, RC39, Sharpea, Solobacterium, Succiniclasticum, and Syntrophococcus were particularly prevalent during acidosis. Determining the metabolic roles of these key genera in the rumens of cattle fed high-grain diets could define a clinical microbial profile associated with ruminal acidosis. PMID:23584771

Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts

PubMed Central

Bushinsky, David A.

2010-01-01

In vivo, metabolic acidosis {decreased pH from decreased bicarbonate concentration ([HCO3−])} increases urine calcium (Ca) without increased intestinal Ca absorption, resulting in a loss of bone Ca. Conversely, respiratory acidosis [decreased pH from increased partial pressure of carbon dioxide (Pco2)] does not appreciably alter Ca homeostasis. In cultured bone, chronic metabolic acidosis (Met) significantly increases cell-mediated net Ca efflux while isohydric respiratory acidosis (Resp) does not. The proton receptor, OGR1, appears critical for cell-mediated, metabolic acid-induced bone resorption. Perfusion of primary bone cells or OGR1-transfected Chinese hamster ovary (CHO) cells with Met induces transient peaks of intracellular Ca (Cai). To determine whether Resp increases Cai, as does Met, we imaged Cai in primary cultures of bone cells. pH for Met = 7.07 ([HCO3−] = 11.8 mM) and for Resp = 7.13 (Pco2 = 88.4 mmHg) were similar and lower than neutral (7.41). Both Met and Resp induced a marked, transient increase in Cai in individual bone cells; however, Met stimulated Cai to a greater extent than Resp. We used OGR1-transfected CHO cells to determine whether OGR1 was responsible for the greater increase in Cai in Met than Resp. Both Met and Resp induced a marked, transient increase in Cai in OGR1-transfected CHO cells; however, in these cells Met was not different than Resp. Thus, the greater induction of Cai by Met in primary bone cells is not a function of OGR1 alone, but must involve H+ receptors other than OGR1, or pathways sensitive to Pco2, HCO3−, or total CO2 that modify the effect of H+ in primary bone cells. PMID:20504884

Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: the role of noninvasive ventilation.

PubMed

Terzano, Claudio; Di Stefano, Fabio; Conti, Vittoria; Di Nicola, Marta; Paone, Gregorino; Petroianni, Angelo; Ricci, Alberto

2012-01-01

Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure. Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO(2) and PaCO(2) and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV. Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis-metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1 ± 9.8, 36.2 ± 8.9 and 53.3 ± 4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis-metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder. Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.

The clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation.

PubMed

Mizota, Toshiyuki; Matsukawa, Shino; Fukagawa, Hiroshi; Daijo, Hiroki; Tanaka, Tomoharu; Chen, Fengshi; Date, Hiroshi; Fukuda, Kazuhiko

2015-08-01

We examined the clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation (post-HSCT), focusing on ventilatory management. We aimed to determine the incidence of oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction in post-HSCT lung transplant recipients, and to explore factors associated with their development. Nineteen consecutive patients who underwent lung transplantation post-HSCT at Kyoto University Hospital (Japan) were retrospectively studied. Data regarding patient characteristics, preoperative examination, and clinical course during anesthetic induction were analyzed. The incidence of oxygen desaturation (SpO2 < 90 %) during anesthetic induction and severe respiratory acidosis (pH < 7.2) after anesthetic induction were 21.1 and 26.3 %, respectively. Reduced dynamic compliance (Cdyn) during mechanical ventilation was significantly associated with oxygen desaturation during anesthetic induction (p = 0.01), as well as severe respiratory acidosis after anesthetic induction (p = 0.01). The preoperative partial pressure of carbon dioxide in arterial blood (PaCO2; r = -0.743, p = 0.002) and body mass index (BMI; r = 0.61, p = 0.021) significantly correlated with Cdyn, and multivariate analysis revealed that both PaCO2 and BMI were independently associated with Cdyn. Oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction frequently occur in post-HSCT lung transplant recipients. Low Cdyn may, at least partially, explain oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction. Moreover, preoperative hypercapnia and low BMI were predictive of low Cdyn.

Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts.

PubMed

Frick, Kevin K; Bushinsky, David A

2010-08-01

In vivo, metabolic acidosis {decreased pH from decreased bicarbonate concentration ([HCO(3)(-)])} increases urine calcium (Ca) without increased intestinal Ca absorption, resulting in a loss of bone Ca. Conversely, respiratory acidosis [decreased pH from increased partial pressure of carbon dioxide (Pco(2))] does not appreciably alter Ca homeostasis. In cultured bone, chronic metabolic acidosis (Met) significantly increases cell-mediated net Ca efflux while isohydric respiratory acidosis (Resp) does not. The proton receptor, OGR1, appears critical for cell-mediated, metabolic acid-induced bone resorption. Perfusion of primary bone cells or OGR1-transfected Chinese hamster ovary (CHO) cells with Met induces transient peaks of intracellular Ca (Ca(i)). To determine whether Resp increases Ca(i), as does Met, we imaged Ca(i) in primary cultures of bone cells. pH for Met = 7.07 ([HCO(3)(-)] = 11.8 mM) and for Resp = 7.13 (Pco(2) = 88.4 mmHg) were similar and lower than neutral (7.41). Both Met and Resp induced a marked, transient increase in Ca(i) in individual bone cells; however, Met stimulated Ca(i) to a greater extent than Resp. We used OGR1-transfected CHO cells to determine whether OGR1 was responsible for the greater increase in Ca(i) in Met than Resp. Both Met and Resp induced a marked, transient increase in Ca(i) in OGR1-transfected CHO cells; however, in these cells Met was not different than Resp. Thus, the greater induction of Ca(i) by Met in primary bone cells is not a function of OGR1 alone, but must involve H(+) receptors other than OGR1, or pathways sensitive to Pco(2), HCO(3)(-), or total CO(2) that modify the effect of H(+) in primary bone cells.

Acidosis-Induced Changes in Proteome Patterns of the Prostate Cancer-Derived Tumor Cell Line AT-1.

PubMed

Ihling, Angelika; Ihling, Christian H; Sinz, Andrea; Gekle, Michael

2015-09-04

Under various pathological conditions, such as inflammation, ischemia and in solid tumors, physiological parameters (local oxygen tension or extracellular pH) show distinct tissue abnormalities (hypoxia and acidosis). For tumors, the prevailing microenvironment exerts a strong influence on the phenotype with respect to proliferation, invasion, and metastasis formation and therefore influences prognosis. In this study, we investigate the impact of extracellular metabolic acidosis (pH 7.4 versus 6.6) on the proteome patterns of a prostate cancer-derived tumor cell type (AT-1) using isobaric labeling and LC-MS/MS analysis. In total, 2710 proteins were identified and quantified across four biological replicates, of which seven were significantly affected with changes >50% and used for validation. Glucose transporter 1 and farnesyl pyrophosphatase were found to be down-regulated after 48 h of acidic treatment, and metallothionein 2A was reduced after 24 h and returned to control values after 48 h. After 24 and 48 h at pH 6.6, glutathione S transferase A3 and NAD(P)H dehydrogenase 1, cellular retinoic acid-binding protein 2, and Na-bicarbonate transporter 3 levels were found to be increased. The changes in protein levels were confirmed by transcriptome and functional analyses. In addition to the experimental in-depth investigation of proteins with changes >50%, functional profiling (statistical enrichment analysis) including proteins with changes >20% revealed that acidosis upregulates GSH metabolic processes, citric acid cycle, and respiratory electron transport. Metabolism of lipids and cholesterol biosynthesis were downregulated. Our data comprise the first comprehensive report on acidosis-induced changes in proteome patterns of a tumor cell line.

Alkaline Diet and Metabolic Acidosis: Practical Approaches to the Nutritional Management of Chronic Kidney Disease.

PubMed

Rodrigues Neto Angéloco, Larissa; Arces de Souza, Gabriela Cristina; Almeida Romão, Elen; Garcia Chiarello, Paula

2018-05-01

The kidneys play an extremely important role in maintaining the body acid-base balance by excreting nonvolatile acids and regenerating and reabsorbing bicarbonate in the kidney tubules. As the individual loses their kidney function, renal excretion of nonvolatile acid produced by metabolism of the diet is impaired, resulting in low-grade metabolic acidosis. With this in mind, it is relevant to better understand the dietary aspects related to the acid-base balance in chronic kidney disease metabolic acidosis and try to provide possible strategies for the nutritional management of these cases. The type of diet can deeply affect the body by providing acid or base precursors. Generally speaking, foods such as meat, eggs, cheese, and grains increase the production of acid in the organism, whereas fruit and vegetables are alkalizing. On the other hand, milk is considered neutral as well as fats and sugars, which have a small effect on acid-base balance. The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products. Thus metabolic acidosis may be exacerbated by a contemporary Western diet, which delivers a high nonvolatile acid load. The remaining acid is neutralized or stored within the body. Bone and muscle are lost to neutralize the acid and serum bicarbonate falls. Early studies suggest that lowering the dietary acid load with a reduced protein content and vegetable proteins replacements, associated with an increase in fruits and vegetables intake can improve the metabolic parameters of acidosis, preserve bone and muscle, and slow the glomerular filtration rate decline. More studies focusing on the effects of controlled dietary interventions among chronic kidney disease patients are needed to determining the optimal target for nutritional therapy. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Hemodialysis-refractory metformin-associated lactate acidosis with hypoglycemia, hypothermia, and bradycardia in a diabetic patient with belated diagnosis and chronic kidney disease
.

PubMed

Zibar, Lada; Zibar, Karin

2017-04-01

Metformin is a first-line oral antidiabetic therapy for patients with type 2 diabetes mellitus. Metformin-associated lactate acidosis (MALA) is a well-known, life-threatening, but rare side effect of metformin therapy. Chronic kidney disease (CKD) patients have a much greater risk of MALA. We report the case of a severe refractory MALA despite hemodialysis (HD) treatment, associated with hypoglycemia, hypothermia, and bradycardia in a neglected and thus untimely-recognized CKD patient with type 2 diabetes mellitus. Despite the recent rehabilitation of metformin as a treatment of choice for type 2 diabetes mellitus, the drug should be prescribed with caution as it can be associated with life-threatening refractory acidosis, particularly in CKD patients. Moreover, HD treatment could occasionally be ineffective, resulting in a fatal outcome.
.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome mimicking herpes simplex encephalitis on imaging studies.

PubMed

Gieraerts, Christopher; Demaerel, Philippe; Van Damme, Philip; Wilms, Guido

2013-01-01

We present a case in which mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome mimicked the clinical and radiological signs of herpes simplex encephalitis. In a patient with subacute encephalopathy, on computed tomography and magnetic resonance imaging, lesions were present in both temporal lobes extending to both insular regions with sparing of the lentiform nuclei and in both posterior straight and cingulate gyri. Final diagnosis of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome was based on biochemical investigations on cerebrospinal fluid, electromyogram, muscle biopsy, and genetic analysis. On diffusion-weighted imaging, diffusion restriction was present in some parts of the lesions but not throughout the entire lesions. We suggest that this could be an important sign in the differential diagnosis with herpes simplex encephalitis.

Successful correction of D-lactic acid neurotoxicity (drunken lamb syndrome) by bolus administration of oral sodium bicarbonate.

PubMed

Angell, J W; Jones, G L; Voigt, K; Grove-White, D H

2013-08-31

Drunken lamb syndrome (DLS) has recently been described as lamb D-lactic acidosis syndrome (LDLAS). In 2012, 18 lambs aged between 7 days and 28 days with LDLAS were identified. Biochemically, each lamb had a metabolic acidosis characterised by D-lactic acidosis and exhibited clinical signs including: not hyperthermic, no evidence of dehydration, demonstrating an ataxic gait tending to recumbency (DLS) and possibly somnolence. These lambs received 50 mmol of sodium bicarbonate as an 8.4 per cent solution given orally, together with parenteral long-acting amoxicillin. All 18 cases made a full clinical recovery. This study demonstrates a novel effective treatment for a disease that is usually fatal, and also demonstrates a strong correlation between venous plasma bicarbonate concentrations and venous plasma D-lactate concentrations (R(2)=0.49).

[Liver diseases in high-production cows with ruminal acidosis].

PubMed

Ivanov, I B; Mikhaĭlov, G; Pham, T H

1987-01-01

Studied was the relation of the subclinical, recurring, and chronic rumen acidosis, on the one hand, to the disturbed function, resp., injuries of the liver, on the other. Experiments were carried out with a total of 862 high-producing cows, 54 out of which had massive injuries of the liver. Full clinical examination was performed, 22 of the animals being subject to laboratory investigations with regard to the rumen content (pH, infusorial count per 1 cm3 with the differentiation of bacteria, activity with regard to glucose, nitrates, sedimentation, and flotation), blood (whole blood picture, coagulation tests, bilirubin, SGOT, SGPT, serum aldolase, alkaline phosphatase, alkaline reserves, blood sugar), and urine (pH, protein, ketone bodies, sugar, and CSR). It is concluded that three inferences could be drawn, pointing to the relation between recurring rumen acidosis and the liver diseases.

Inhibition of acid-sensing ion channels by levo-tetrahydropalmatine in rat dorsal root ganglion neurons.

PubMed

Liu, Ting-Ting; Qu, Zu-Wei; Qiu, Chun-Yu; Qiu, Fang; Ren, Cuixia; Gan, Xiong; Peng, Fang; Hu, Wang-Ping

2015-02-01

Levo-tetrahydropalmatine (l-THP), a main bioactive Chinese herbal constituent from the genera Stephania and Corydalis, has been in use in clinical practice for years in China as a traditional analgesic agent. However, the mechanism underlying the analgesic action of l-THP is poorly understood. This study shows that l-THP can exert an inhibitory effect on the functional activity of native acid-sensing ion channels (ASICs), which are believed to mediate pain caused by extracellular acidification. l-THP dose dependently decreased the amplitude of proton-gated currents mediated by ASICs in rat dorsal root ganglion (DRG) neurons. l-THP shifted the proton concentration-response curve downward, with a decrease of 40.93% ± 8.45% in the maximum current response to protons, with no significant change in the pH0.5 value. Moreover, l-THP can alter the membrane excitability of rat DRG neurons to acid stimuli. It significantly decreased the number of action potentials and the amplitude of the depolarization induced by an extracellular pH drop. Finally, peripherally administered l-THP inhibited the nociceptive response to intraplantar injection of acetic acid in rats. These results indicate that l-THP can inhibit the functional activity of ASICs in dissociated primary sensory neurons and relieve acidosis-evoked pain in vivo, which for the first time provides a novel peripheral mechanism underlying the analgesic action of l-THP. © 2014 Wiley Periodicals, Inc.

Effect of stress on hepatic 11beta-hydroxysteroid dehydrogenase activity and its influence on carbohydrate metabolism.

PubMed

Altuna, María Eugenia; Lelli, Sandra Marcela; San Martín de Viale, Leonor C; Damasco, María Cristina

2006-10-01

Stress activates the synthesis and secretion of catecholamines and adrenal glucocorticoids, increasing their circulating levels. In vivo, hepatic 11beta-hydroxysteroid dehydrogenase 1 (HSD1) stimulates the shift of 11-dehydrocorticosterone to corticosterone, enhancing active glucocorticoids at tissue level. We studied the effect of 3 types of stress, 1 induced by bucogastric overload with 200 mmol/L HCl causing metabolic acidosis (HCl), the second induced by bucogastric overload with 0.45% NaCl (NaCl), and the third induced by simulated overload (cannula), on the kinetics of hepatic HSD1 of rats and their influence on the activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, glycemia, and glycogen deposition. Compared with unstressed controls, all types of stress significantly increased HSD1 activity (146% cannula, 130% NaCl, and 253% HCl), phosphoenolpyruvate carboxykinase activity (51% cannula, 48% NaCl, and 86% HCl), and glycemia (29% cannula, 30% NaCl, and 41% HCl), but decreased hepatic glycogen (68% cannula, 68% NaCl, and 78% HCl). Owing to these results, we suggest the following events occur when stress is induced: an increase in hepatic HSD1 activity, augmented active glucocorticoid levels, increased gluconeogenesis, and glycemia. Also involved are the multiple events indirectly related to glucocorticoids, which lead to the depletion of hepatic glycogen deposits, thereby contributing to increased glycemia. This new approach shows that stress increments the activity of hepatic HSD1 and suggests that this enzyme could be involved in the development of the Metabolic Syndrome.

Ruminal acidosis in a 21-month-old Holstein heifer

PubMed Central

Golder, Helen M.; Celi, Pietro; Lean, Ian J.

2014-01-01

Rumen and blood biochemical profiles were monitored in 8 Holstein heifers exposed to a carbohydrate feeding challenge. One of the heifers had clinical signs consistent with acute ruminal acidosis on the day of, and subsequent to, the challenge. Within 24 h of challenge, 6 of 7 rumen volatile fatty acids measured were not detectable in this heifer and her rumen total lactate concentration was > 70 mM. PMID:24891639

Information Theory to Probe Intrapartum Fetal Heart Rate Dynamics

NASA Astrophysics Data System (ADS)

Granero-Belinchon, Carlos; Roux, Stéphane; Abry, Patrice; Doret, Muriel; Garnier, Nicolas

2017-11-01

Intrapartum fetal heart rate (FHR) monitoring constitutes a reference tool in clinical practice to assess the baby health status and to detect fetal acidosis. It is usually analyzed by visual inspection grounded on FIGO criteria. Characterization of Intrapartum fetal heart rate temporal dynamics remains a challenging task and continuously receives academic research efforts. Complexity measures, often implemented with tools referred to as \\emph{Approximate Entropy} (ApEn) or \\emph{Sample Entropy} (SampEn), have regularly been reported as significant features for intrapartum FHR analysis. We explore how Information Theory, and especially {\\em auto mutual information} (AMI), is connected to ApEn and SampEn and can be used to probe FHR dynamics. Applied to a large (1404 subjects) and documented database of FHR data, collected in a French academic hospital, it is shown that i) auto mutual information outperforms ApEn and SampEn for acidosis detection in the first stage of labor and continues to yield the best performance in the second stage; ii) Shannon entropy increases as labor progresses, and is always much larger in the second stage;iii) babies suffering from fetal acidosis additionally show more structured temporal dynamics than healthy ones and that this progressive structuration can be used for early acidosis detection.

Association between serum bicarbonate and pH with depression, cognition and sleep quality in hemodialysis patients.

PubMed

Afsar, Baris; Elsurer, Rengin

2015-07-01

Metabolic acidosis is a common feature in chronic renal failure patients, worsening progressively as renal function declines. There are conflicting data in hemodialysis (HD) patients with regard to acidosis, alkalosis and mortality. In HD patients, cognitive impairment, depression, sleep disorders and impaired quality of life are very common. Besides, these conditions are related with increased morbidity and mortality. However, no previous study investigated the relationship between pH, venous bicarbonate and anion gap with depression, sleep problems and cognitive function in HD patients. In this study we investigated these relationships. In total, 65 HD patients were included. The demographic parameters and laboratory parameters including bicarbonate, pH and anion gap was measured for all patients. Depressive symptoms, sleep quality and cognitive function, were measured by Beck depression inventory, The Pittsburgh Sleep Quality Index and by Mini Mental State Examination, respectively. We found that, sleep quality but not cognitive function or depression was independently related with venous pH and bicarbonate. Anion gap has no independent relationship with sleep quality, cognitive function and depression. In conclusion, metabolic acidosis and bicarbonate levels were independently related with sleep quality in HD patients. However, there was no association between metabolic acidosis and bicarbonate levels with cognitive function and depression.

Transient 5-oxoprolinuria: unusually high anion gap acidosis in an infant.

PubMed

Hulley, Sarah L; Perring, Jeff; Manning, Nigel; Olpin, Simon; Yap, Sufin

2015-12-01

Transient 5-oxoprolinuria is a phenomenon that is well recognised in adults. We illustrate an unusual paediatric case of transient 5-oxoprolinuria presenting during an episode of severe sepsis with concomitant paracetamol use. The 15-month-old patient had an extremely high anion gap metabolic acidosis. Adequate resuscitation failed to correct the biochemical disturbance, and high levels of 5-oxoproline were identified. A combination of haemofiltration, replenishment of glutathione stores with N-acetylcysteine and cessation of paracetamol administration resulted in the resolution of the acidosis. Subsequent testing following treatment of the sepsis revealed no ongoing 5-oxoprolinuria. Transient 5-oxoprolinuria has been previously reported in the adult population during episodes of severe sepsis and various pharmaceutical interventions. This case illustrates that it is a phenomenon that should be considered in paediatric patients where a very high anion gap metabolic acidosis exists that cannot be explained by the biochemical indices. • 5-oxoprolinuria in the paediatric population is usually secondary to an inborn error of metabolism. • Transient 5-oxoprolinuria is well recognised in adults during episodes of severe glutathione depletion. • Transient 5-oxoprolinuria is a phenomenon rarely reported in the paediatric population. • It highlights the importance of investigating a high anion gap such that unusual diagnoses are not missed.

Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers

PubMed Central

Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica

2014-01-01

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response. PMID:25013355

Ruminal acidosis and the rapid onset of ruminal parakeratosis in a mature dairy cow: a case report

PubMed Central

Steele, Michael A; AlZahal, Ousama; Hook, Sarah E; Croom, Jim; McBride, Brian W

2009-01-01

A mature dairy cow was transitioned from a high forage (100% forage) to a high-grain (79% grain) diet over seven days. Continuous ruminal pH recordings were utilized to diagnose the severity of ruminal acidosis. Additionally, blood and rumen papillae biopsies were collected to describe the structural and functional adaptations of the rumen epithelium. On the final day of the grain challenge, the daily mean ruminal pH was 5.41 ± 0.09 with a minimum of 4.89 and a maximum of 6.31. Ruminal pH was under 5.0 for 130 minutes (2.17 hours) which is characterized as the acute form of ruminal acidosis in cattle. The grain challenge increased blood beta-hydroxybutyrate by 1.8 times and rumen papillae mRNA expression of 3-hydroxy-3-methylglutaryl-coenzyme A synthase by 1.6 times. Ultrastructural and histological adaptations of the rumen epithelium were imaged by scanning electron and light microscopy. Rumen papillae from the high grain diet displayed extensive sloughing of the stratum corneum and compromised cell adhesion as large gaps were apparent between cells throughout the strata. This case report represents a rare documentation of how the rumen epithelium alters its function and structure during the initial stage of acute acidosis. PMID:19840395

Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers.

PubMed

Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica; Burgos, Rafael Agustín

2014-01-01

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response.

Diet-Induced Low-Grade Metabolic Acidosis and Clinical Outcomes: A Review

PubMed Central

Carnauba, Renata Alves; Baptistella, Ana Beatriz; Paschoal, Valéria; Hübscher, Gilberti Helena

2017-01-01

Low-grade metabolic acidosis is a condition characterized by a slight decrease in blood pH, within the range considered normal, and feeding is one of the main factors that may influence the occurrence of such a condition. The excessive consumption of acid precursor foods (sources of phosphorus and proteins), to the detriment of those precursors of bases (sources of potassium, calcium, and magnesium), leads to acid-base balance volubility. If this condition occurs in a prolonged, chronic way, low-grade metabolic acidosis can become significant and predispose to metabolic imbalances such as kidney stone formation, increased bone resorption, reduced bone mineral density, and the loss of muscle mass, as well as the increased risk of chronic diseases such as type 2 diabetes mellitus, hypertension, and non-alcoholic hepatic steatosis. Considering the increase in the number of studies investigating the influence of diet-induced metabolic acidosis on clinical outcomes, this review gathers the available evidence evaluating the association of this disturbance and metabolic imbalances, as well as related mechanisms. It is necessary to look at the western dietary pattern of most countries and the increasing incidence of non-comunicable diseases for the balance between fruit and vegetable intake and the appropriate supply of protein, mainly from animal sources, so that it does not exceed the daily recommendations. PMID:28587067

Hypercapnia induced shifts in gill energy budgets of Antarctic notothenioids.

PubMed

Deigweiher, Katrin; Hirse, Timo; Bock, Christian; Lucassen, Magnus; Pörtner, Hans O

2010-03-01

Mechanisms responsive to hypercapnia (elevated CO(2) concentrations) and shaping branchial energy turnover were investigated in isolated perfused gills of two Antarctic Notothenioids (Gobionotothen gibberifrons, Notothenia coriiceps). Branchial oxygen consumption was measured under normo- versus hypercapnic conditions (10,000 ppm CO(2)) at high extracellular pH values. The fractional costs of ion regulation, protein and RNA synthesis in the energy budgets were determined using specific inhibitors. Overall gill energy turnover was maintained under pH compensated hypercapnia in both Antarctic species as well as in a temperate zoarcid (Zoarces viviparus). However, fractional energy consumption by the examined processes rose drastically in G. gibberifrons (100-180%), and to a lesser extent in N. coriiceps gills (7-56%). In conclusion, high CO(2) concentrations under conditions of compensated acidosis induce cost increments in epithelial processes, however, at maintained overall rates of branchial energy turnover.

Yam bean seed poisoning mimicking cyanide intoxication.

PubMed

Hung, Y-M; Hung, S-Y; Olson, K R; Chou, K-J; Lin, S-L; Chung, H-M; Tung, C-N; Chang, J-C

2007-02-01

Yam bean is a common food in southern Taiwan. However, its seeds are rarely consumed. We describe five patients of yam bean seed poisoning in Taiwan, one of them life-threatening. The five patients presented with perioral numbness, nausea and vomiting after eating a same soup made from yam bean seeds. One of them, a 54-year-old woman, had difficulty breathing and lost consciousness. Physical examination showed dilated pupils and coma with no focal neurological signs. The initial blood pressure was normal. Laboratory data showed a severe anion gap metabolic acidosis, with a serum lactate level of 185 mg/dL. An initial diagnosis of cyanide intoxication was considered and she was given sodium nitrite and sodium thiosulfate i.v. Hypotension ensued shortly afterwards and pulmonary artery catheterization showed a decreased cardiac index. Aggressive fluid and inotropic therapy were given and the patient eventually recovered. The other four patients suffered only minor gastrointestinal and neurological symptoms and received supportive treatment. Cyanide levels were negative in all five patients. Yam bean seed poisoning can cause acute metabolic acidosis and altered mental status, which could be confused with acute cyanide intoxication from a cyanogenic glycoside-containing plant. To our knowledge, this is the first outbreak of yam bean seed poisoning reported in the English published work.

Impaired trafficking of human kidney anion exchanger (kAE1) caused by hetero-oligomer formation with a truncated mutant associated with distal renal tubular acidosis.

PubMed

Quilty, Janne A; Cordat, Emmanuelle; Reithmeier, Reinhart A F

2002-12-15

Autosomal dominant distal renal tubular acidosis (dRTA) has been associated with several mutations in the anion exchanger AE1 gene. The effect of an 11-amino-acid C-terminal dRTA truncation mutation (901 stop) on the expression of kidney AE1 (kAE1) and erythroid AE1 was examined in transiently transfected HEK-293 cells. Unlike the wild-type proteins, kAE1 901 stop and AE1 901 stop mutants exhibited impaired trafficking from the endoplasmic reticulum to the plasma membrane as determined by immunolocalization, cell-surface biotinylation, oligosaccharide processing and pulse-chase experiments. The 901 stop mutants were able to bind to an inhibitor affinity resin, suggesting that these mutant membrane proteins were not grossly misfolded. Co-expression of wild-type and mutant kAE1 or AE1 resulted in intracellular retention of the wild-type proteins in a pre-medial Golgi compartment. This dominant negative effect was due to hetero-oligomer formation of the mutant and wild-type proteins. Intracellular retention of kAE1 in the alpha-intercalated cells of the kidney would account for the impaired acid secretion into the urine characteristic of dRTA.

MITOCHONDRIAL DNA DEPLETION SYNDROME DUE TO MUTATIONS IN THE RRM2B GENE

PubMed Central

Bornstein, Belén; Area, Estela; Flanigan, Kevin M.; Ganesh, Jaya; Jayakar, Parul; Swoboda, Kathryn J.; Coku, Jorida; Naini, Ali; Shanske, Sara; Tanji, Kurenai; Hirano, Michio; DiMauro, Salvatore

2014-01-01

Mitochondrial DNA depletion syndrome (MDS) is characterized by a reduction in mtDNA copy number and has been associated with mutations in eight nuclear genes, including enzymes involved in mitochondrial nucleotide metabolism (POLG, TK2, DGUOK, SUCLA2, SUCLG1, PEO1) and MPV17. Recently, mutations in The RRM2B gene, encoding the p53-controlled ribonucleotide reductase subunit, have been described in 7 infants from 4 families, who presented with various combinations of hypotonia, tubulopathy, seizures, respiratory distress, diarrhea, and lactic acidosis. All children died before 4 months of age. We sequenced the RRM2B gene in three unrelated cases with unexplained severe mtDNA depletion. The first patient developed intractable diarrhea, profound weakness, respiratory distress, and died at three months. The other two unrelated patients had a much milder phenotype and are still alive at ages 27 and 36 months. All three patients had lactic acidosis and severe depletion of mtDNA in muscle. Muscle histochemistry showed RRF and COX deficiency. Sequencing the RRM2B gene revealed three missense mutations and two single nucleotide deletions in exon 6, 8 and 9, confirming that RRM2B mutations are important causes of MDS and that the clinical phenotype is heterogeneous and not invariably fatal in infancy. PMID:18504129

Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene.

PubMed

Bornstein, Belén; Area, Estela; Flanigan, Kevin M; Ganesh, Jaya; Jayakar, Parul; Swoboda, Kathryn J; Coku, Jorida; Naini, Ali; Shanske, Sara; Tanji, Kurenai; Hirano, Michio; DiMauro, Salvatore

2008-06-01

Mitochondrial DNA depletion syndrome (MDS) is characterized by a reduction in mtDNA copy number and has been associated with mutations in eight nuclear genes, including enzymes involved in mitochondrial nucleotide metabolism (POLG, TK2, DGUOK, SUCLA2, SUCLG1, PEO1) and MPV17. Recently, mutations in the RRM2B gene, encoding the p53-controlled ribonucleotide reductase subunit, have been described in seven infants from four families, who presented with various combinations of hypotonia, tubulopathy, seizures, respiratory distress, diarrhea, and lactic acidosis. All children died before 4 months of age. We sequenced the RRM2B gene in three unrelated cases with unexplained severe mtDNA depletion. The first patient developed intractable diarrhea, profound weakness, respiratory distress, and died at 3 months. The other two unrelated patients had a much milder phenotype and are still alive at ages 27 and 36 months. All three patients had lactic acidosis and severe depletion of mtDNA in muscle. Muscle histochemistry showed RRF and COX deficiency. Sequencing the RRM2B gene revealed three missense mutations and two single nucleotide deletions in exons 6, 8, and 9, confirming that RRM2B mutations are important causes of MDS and that the clinical phenotype is heterogeneous and not invariably fatal in infancy.

Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome.

PubMed

Sproule, Douglas M; Kaufmann, Petra

2008-10-01

Since the initial description almost 25 years ago, the syndrome of mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) has been a useful model to study the complex interplay of factors that define mitochondrial disease. This syndrome, most commonly caused by an A-to-G transition mutation at position 3243 of the mitochondrial genome, is typified by characteristic neurological manifestations including seizures, encephalopathy, and strokelike episodes, as well as other frequent secondary manifestations including short stature, cognitive impairment, migraines, depression, cardiomyopathy, cardiac conduction defects, and diabetes mellitus. In this review, we discuss the history, pathogenesis, clinical features, and diagnostic and management strategies of mitochondrial disease in general and of MELAS in particular. We explore features of mitochondrial genetics, including the concepts of heteroplasmy, mitotic segregation, and threshold effect, as a basis for understanding the variability and complicated inheritance patterns seen with this group of diseases. We also describe systemic manifestations of MELAS-associated mutations, including cardiac, renal, endocrine, gastrointestinal, and endothelial abnormalities and pathology, as well as the hypothetical role of derangements to COX enzymatic function in driving the unique pathology and clinical manifestations of MELAS. Although therapeutic options for MELAS and other mitochondrial diseases remain limited, and recent trials have been disappointing, we also consider current and potential therapeutic modalities.

Hypercapnic acidosis modulates inflammation, lung mechanics, and edema in the isolated perfused lung.

PubMed

De Smet, Hilde R; Bersten, Andrew D; Barr, Heather A; Doyle, Ian R

2007-12-01

Low tidal volume (V(T)) ventilation strategies may be associated with permissive hypercapnia, which has been shown by ex vivo and in vivo studies to have protective effects. We hypothesized that hypercapnic acidosis may be synergistic with low V(T) ventilation; therefore, we studied the effects of hypercapnia and V(T) on unstimulated and lipopolysaccharide-stimulated isolated perfused lungs. Isolated perfused rat lungs were ventilated for 2 hours with low (7 mL/kg) or moderately high (20 mL/kg) V(T) and 5% or 20% CO(2), with lipopolysaccharide or saline added to the perfusate. Hypercapnia resulted in reduced pulmonary edema, lung stiffness, tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the lavage and perfusate. The moderately high V(T) did not cause lung injury but increased lavage IL-6 and perfusate IL-6 as well as TNF-alpha. Pulmonary edema and respiratory mechanics improved, possibly as a result of a stretch-induced increase in surfactant turnover. Lipopolysaccharide did not induce significant lung injury. We conclude that hypercapnia exerts a protective effect by modulating inflammation, lung mechanics, and edema. The moderately high V(T) used in this study stimulated inflammation but paradoxically improved edema and lung mechanics with an associated increase in surfactant release.

Clinical manifestations and management of four children with Pearson syndrome.

PubMed

Tumino, Manuela; Meli, Concetta; Farruggia, Piero; La Spina, Milena; Faraci, Maura; Castana, Cinzia; Di Raimondo, Vincenzo; Alfano, Marivana; Pittalà, Annarita; Lo Nigro, Luca; Russo, Giovanna; Di Cataldo, Andrea

2011-12-01

Pearson marrow-pancreas syndrome is a fatal disorder mostly diagnosed during infancy and caused by mutations of mitochondrial DNA. We hereby report on four children affected by Pearson syndrome with hematological disorders at onset. The disease was fatal to three of them and the fourth one, who received hematopoietic stem cell transplantation, died of secondary malignancy. In this latter patient transplantation corrected hematological and non-hematological issues like metabolic acidosis, and we therefore argue that it could be considered as a useful option in an early stage of the disease. Copyright © 2011 Wiley Periodicals, Inc.

Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors.

PubMed

Sebastian, Anthony; Frassetto, Lynda A; Sellmeyer, Deborah E; Merriam, Renée L; Morris, R Curtis

2002-12-01

Natural selection has had < 1% of hominid evolutionary time to eliminate the inevitable maladaptations consequent to the profound transformation of the human diet resulting from the inventions of agriculture and animal husbandry. The objective was to estimate the net systemic load of acid (net endogenous acid production; NEAP) from retrojected ancestral preagricultural diets and to compare it with that of contemporary diets, which are characterized by an imbalance of nutrient precursors of hydrogen and bicarbonate ions that induces a lifelong, low-grade, pathogenically significant systemic metabolic acidosis. Using established computational methods, we computed NEAP for a large number of retrojected ancestral preagricultural diets and compared them with computed and measured values for typical American diets. The mean (+/- SD) NEAP for 159 retrojected preagricultural diets was -88 +/- 82 mEq/d; 87% were net base-producing. The computational model predicted NEAP for the average American diet (as recorded in the third National Health and Nutrition Examination Survey) as 48 mEq/d, within a few percentage points of published measured values for free-living Americans; the model, therefore, was not biased toward generating negative NEAP values. The historical shift from negative to positive NEAP was accounted for by the displacement of high-bicarbonate-yielding plant foods in the ancestral diet by cereal grains and energy-dense, nutrient-poor foods in the contemporary diet-neither of which are net base-producing. The findings suggest that diet-induced metabolic acidosis and its sequelae in humans eating contemporary diets reflect a mismatch between the nutrient composition of the diet and genetically determined nutritional requirements for optimal systemic acid-base status.

Probiotics, D–Lactic acidosis, oxidative stress and strain specificity

PubMed Central

2017-01-01

ABSTRACT The existence of an implicit living microscopic world, composed primarily of bacteria, has been known for centuries. The exact mechanisms that govern the contribution of bacteria to human health and disease have only recently become the subject of intense research efforts. Within this very evident shift in paradigms, the rational design of probiotic formulations has led to the creation of an industry that seeks to progress the engineering of probiotic bacteria that produce metabolites that may enhance human host health and prevent disease. The promotion of probiotics is often made in the absence of quality scientific and clinically plausible data. The latest incursions into the probiotic market of claims have posited the amelioration of oxidative stress via potent antioxidant attributes or limiting the administration of probiotics to those species that do not produce D-Lactic acid (i.e., claims that D-Lactic acid acidosis is linked to chronic health conditions) or are strain-specific (shaping an industry point of difference) for appraising a therapeutic effect. Evidence-based research should guide clinical practice, as there is no place in science and medicine that supports unsubstantiated claims. Extravagant industry based notions continue to fuel the imprimatur of distrust and skepticism that is leveled by scientists and clinicians at an industry that is already rife with scientific and medical distrust and questionable views on probiotics. Ignoring scientifically discordant data, when sorting through research innovations and false leads relevant to the actions of probiotics, drives researcher discomfit and keeps the bar low, impeding the progress of knowledge. Biologically plausible posits are obligatory in any research effort; companies formulating probiotics often exhibit a lack of analytical understanding that then fuels questionable investigations failing to build on research capacity. PMID:28080206

Quantification of in vivo pH-weighted amide proton transfer (APT) MRI in acute ischemic stroke

NASA Astrophysics Data System (ADS)

Zhou, Iris Y.; Igarashi, Takahiro; Guo, Yingkun; Sun, Phillip Z.

2015-03-01

Amide proton transfer (APT) imaging is a specific form of chemical exchange saturation transfer (CEST) MRI that probes the pH-dependent amide proton exchange.The endogenous APT MRI is sensitive to tissue acidosis, which may complement the commonly used perfusion and diffusion scans for characterizing heterogeneous ischemic tissue damage. Whereas the saturation transfer asymmetry analysis (MTRasym) may reasonably compensate for direct RF saturation, in vivo MTRasym is however, susceptible to an intrinsically asymmetric shift (MTR'asym). Specifically, the reference scan for the endogenous APT MRI is 7 ppm upfield from that of the label scan, and subjects to concomitant RF irradiation effects, including nuclear overhauser effect (NOE)-mediated saturation transfer and semisolid macromolecular magnetization transfer. As such, the commonly used asymmetry analysis could not fully compensate for such slightly asymmetric concomitant RF irradiation effects, and MTRasym has to be delineated in order to properly characterize the pH-weighted APT MRI contrast. Given that there is very little change in relaxation time immediately after ischemia and the concomitant RF irradiation effects only minimally depends on pH, the APT contrast can be obtained as the difference of MTRasym between the normal and ischemic regions. Thereby, the endogenous amide proton concentration and exchange rate can be solved using a dual 2-pool model, and the in vivo MTR'asym can be calculated by subtracting the solved APT contrast from asymmetry analysis (i.e., MTR'asym =MTRasym-APTR). In addition, MTR'asym can be quantified using the classical 2-pool exchange model. In sum, our study delineated the conventional in vivo pH-sensitive MTRasym contrast so that pHspecific contrast can be obtained for imaging ischemic tissue acidosis.

Rumen microbial abundance and fermentation profile during severe subacute ruminal acidosis and its modulation by plant derived alkaloids in vitro.

PubMed

Mickdam, Elsayed; Khiaosa-Ard, Ratchaneewan; Metzler-Zebeli, Barbara U; Klevenhusen, Fenja; Chizzola, Remigius; Zebeli, Qendrim

2016-06-01

Rumen microbiota have important metabolic functions for the host animal. This study aimed at characterizing changes in rumen microbial abundances and fermentation profiles using a severe subacute ruminal acidosis (SARA) in vitro model, and to evaluate a potential modulatory role of plant derived alkaloids (PDA), containing quaternary benzophenanthridine and protopine alkaloids, of which sanguinarine and chelerythrine were the major bioactive compounds. Induction of severe SARA strongly affected the rumen microbial composition and fermentation variables without suppressing the abundance of total bacteria. Protozoa and fungi were more sensitive to the low ruminal pH condition than bacteria. Induction of severe SARA clearly depressed degradation of fiber (P < 0.001), which came along with a decreased relative abundance of fibrolytic Ruminococcus albus and Fibrobacter succinogenes (P < 0.001). Under severe SARA conditions, the genus Prevotella, Lactobacillus group, Megasphaera elsdenii, and Entodinium spp. (P < 0.001) were more abundant, whereas Ruminobacter amylophilus was less abundant. SARA largely suppressed methane formation (-70%, P < 0.001), although total methanogenic 16S rRNA gene abundance was not affected. According to principal component analysis, Methanobrevibacter spp. correlated to methane concentration. Addition of PDA modulated ruminal fermentation under normal conditions such as enhanced (P < 0.05) concentration of total SCFA, propionate and valerate, and increased (P < 0.05) degradation of crude protein compared with the unsupplemented control diet. Our results indicate strong shifts in the microbial community during severe SARA compared to normal conditions. Supplementation of PDA positively modulates ruminal fermentation under normal ruminal pH conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Probiotics, D-Lactic acidosis, oxidative stress and strain specificity.

PubMed

Vitetta, Luis; Coulson, Samantha; Thomsen, Michael; Nguyen, Tony; Hall, Sean

2017-07-04

The existence of an implicit living microscopic world, composed primarily of bacteria, has been known for centuries. The exact mechanisms that govern the contribution of bacteria to human health and disease have only recently become the subject of intense research efforts. Within this very evident shift in paradigms, the rational design of probiotic formulations has led to the creation of an industry that seeks to progress the engineering of probiotic bacteria that produce metabolites that may enhance human host health and prevent disease. The promotion of probiotics is often made in the absence of quality scientific and clinically plausible data. The latest incursions into the probiotic market of claims have posited the amelioration of oxidative stress via potent antioxidant attributes or limiting the administration of probiotics to those species that do not produce D-Lactic acid (i.e., claims that D-Lactic acid acidosis is linked to chronic health conditions) or are strain-specific (shaping an industry point of difference) for appraising a therapeutic effect. Evidence-based research should guide clinical practice, as there is no place in science and medicine that supports unsubstantiated claims. Extravagant industry based notions continue to fuel the imprimatur of distrust and skepticism that is leveled by scientists and clinicians at an industry that is already rife with scientific and medical distrust and questionable views on probiotics. Ignoring scientifically discordant data, when sorting through research innovations and false leads relevant to the actions of probiotics, drives researcher discomfit and keeps the bar low, impeding the progress of knowledge. Biologically plausible posits are obligatory in any research effort; companies formulating probiotics often exhibit a lack of analytical understanding that then fuels questionable investigations failing to build on research capacity.

Leigh syndrome caused by a novel m.4296G>A mutation in mitochondrial tRNA isoleucine.

PubMed

Cox, Rachel; Platt, Julia; Chen, Li Chieh; Tang, Sha; Wong, Lee-Jun; Enns, Gregory M

2012-03-01

Leigh syndrome is a severe neurodegenerative disease with heterogeneous genetic etiology. We report a novel m.4296G>A variant in the mitochondrial tRNA isoleucine gene in a child with Leigh syndrome, mitochondrial proliferation, lactic acidosis, and abnormal respiratory chain enzymology. The variant is present at >75% heteroplasmy in blood and cultured fibroblasts from the proband, <5% in asymptomatic maternal relatives, and is absent in 3000 controls. It is located in the highly conserved anticodon region of tRNA(Ile) where three other pathogenic changes have been described. We conclude that there is strong evidence to classify m.4296G>A as a pathogenic mutation causing Leigh syndrome. Copyright © 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Neurological Complications Resulting from Non-Oral Occupational Methanol Poisoning.

PubMed

Choi, Ji Hyun; Lee, Seung Keun; Gil, Young Eun; Ryu, Jia; Jung-Choi, Kyunghee; Kim, Hyunjoo; Choi, Jun Young; Park, Sun Ah; Lee, Hyang Woon; Yun, Ji Young

2017-02-01

Methanol poisoning results in neurological complications including visual disturbances, bilateral putaminal hemorrhagic necrosis, parkinsonism, cerebral edema, coma, or seizures. Almost all reported cases of methanol poisoning are caused by oral ingestion of methanol. However, recently there was an outbreak of methanol poisoning via non-oral exposure that resulted in severe neurological complications to a few workers at industrial sites in Korea. We present 3 patients who had severe neurological complications resulting from non-oral occupational methanol poisoning. Even though initial metabolic acidosis and mental changes were improved with hemodialysis, all of the 3 patients presented optic atrophy and ataxia or parkinsonism as neurological complications resulting from methanol poisoning. In order to manage it adequately, as well as to prevent it, physicians should recognize that methanol poisoning by non-oral exposure can cause neurologic complications.

A case of Kombucha tea toxicity.

PubMed

SungHee Kole, Alison; Jones, Heather D; Christensen, Russell; Gladstein, Jay

2009-01-01

Kombucha "mushroom'' tea is touted to have medicinal properties. Here, we present a case of hyperthermia, lactic acidosis, and acute renal failure within 15 hours of Kombucha tea ingestion. A 22 year old male, newly diagnosed with HIV, became short of breath and febrile to 103.0F, within twelve hours of Kombucha tea ingestion. He subsequently became combative and confused, requiring sedation and intubation for airway control. Laboratories revealed a lactate of 12.9 mmol/L, and serum creatinine of 2.1 mg/dL. Kombucha tea is black tea fermented in a yeast-bacteria medium. Several case reports exist of serious, and sometimes fatal, hepatic dysfunction and lactic acidosis within close proximity to ingestion. While Kombucha tea is considered a healthy elixir, the limited evidence currently available raises considerable concern that it may pose serious health risks. Consumption of this tea should be discouraged, as it may be associated with life-threatening lactic acidosis.

Intestinal microbial and metabolic alterations following successful fecal microbiota transplant for D-lactic acidosis.

PubMed

Bulik-Sullivan, Emily C; Roy, Sayanty; Elliott, Ryan J; Kassam, Zain; Lichtman, Steven N; Carroll, Ian M; Gulati, Ajay S

2018-06-12

Fecal microbiota transplantation (FMT) involves the transfer of stool from a healthy individual into the intestinal tract of a diseased recipient. Although used primarily for recurrent Clostridium difficile infection, FMT is increasingly being attempted as an experimental therapy for other illnesses, including metabolic disorders. D-lactic acidosis (D-LA) is a metabolic disorder that may occur in individuals with short bowel syndrome when lactate-producing bacteria in the colon overproduce D-lactate. This results in elevated systemic levels of D-lactate, metabolic acidosis, and encephalopathy. In this study, we report the successful use of FMT for the treatment of recurrent D-LA in a child who was unresponsive to conventional therapies. Importantly, we also present profiles of the enteric microbiota, as well as fecal D-/L-lactic acid metabolites, before and longitudinally after FMT. These data provide valuable insight into the putative mechanisms of D-LA pathogenesis and its treatment.

Acidosis overrides oxygen deprivation to maintain mitochondrial function and cell survival

PubMed Central

Khacho, Mireille; Tarabay, Michelle; Patten, David; Khacho, Pamela; MacLaurin, Jason G.; Guadagno, Jennifer; Bergeron, Richard; Cregan, Sean P.; Harper, Mary-Ellen; Park, David S.; Slack, Ruth S.

2014-01-01

Sustained cellular function and viability of high-energy demanding post-mitotic cells rely on the continuous supply of ATP. The utilization of mitochondrial oxidative phosphorylation for efficient ATP generation is a function of oxygen levels. As such, oxygen deprivation, in physiological or pathological settings, has profound effects on cell metabolism and survival. Here we show that mild extracellular acidosis, a physiological consequence of anaerobic metabolism, can reprogramme the mitochondrial metabolic pathway to preserve efficient ATP production regardless of oxygen levels. Acidosis initiates a rapid and reversible homeostatic programme that restructures mitochondria, by regulating mitochondrial dynamics and cristae architecture, to reconfigure mitochondrial efficiency, maintain mitochondrial function and cell survival. Preventing mitochondrial remodelling results in mitochondrial dysfunction, fragmentation and cell death. Our findings challenge the notion that oxygen availability is a key limiting factor in oxidative metabolism and brings forth the concept that mitochondrial morphology can dictate the bioenergetic status of post-mitotic cells. PMID:24686499

[The role of lactate acidosis in the development and treatment of various neurologic syndromes in children and adolescents].

PubMed

Arveladze, G A; Geladze, N M; Sanikidze, T B; Khachapuridze, N S; Bakhtadze, S Z

2015-02-01

The aim of the study was to detect the role of lactate acidosis, also to find the share of mitochondrial insufficiency in development of various neurologic syndromes in children and adolescents. The detection of cellular energetic metabolism and acid based imbalance is also important for finding the specific method of management. We have studied 200 patients with various degree of neurodevelopment delay with epilepsy and epileptic syndromes, headache, vertigo, early strokes, floppy infant syndrome, atrophy of ophthalmic nerve, cataracta, neurosensory deafness, systemic myopathy, cerebral palsy. In 27% of cases with various ages we have detected lactate acidosis and increase level of pyruvate. Mitochondrial insufficiency was seen in 8% of cases which gives us opportunity to find the specific method of treatment in this group of patients. Each patient with neurological symptoms requires correction of parameters of energetic and oxidative metabolism.

Comparison of the effects of moderate and severe hypercapnic acidosis on ventilation-induced lung injury.

PubMed

Yang, Wanchao; Yue, Ziyong; Cui, Xiaoguang; Guo, Yueping; Zhang, Lili; Zhou, Huacheng; Li, Wenzhi

2015-04-30

We have proved that hypercapnic acidosis (a PaCO2 of 80-100 mmHg) protects against ventilator-induced lung injury in rats. However, there remains uncertainty regarding the appropriate target PaCO2 or if greater CO2 "doses" (PaCO2 > 100 mmHg) demonstrate this effect. We wished to determine whether severe acute hypercapnic acidosis can reduce stretch-induced injury, as well as the role of nuclear factor-κB (NF-κB) in the effects of acute hypercapnic acidosis. Fifty-four rats were ventilated for 4 hours with a pressure-controlled ventilation mode set at a peak inspiratory pressure (PIP) of 30 cmH2O. A gas mixture of carbon dioxide with oxygen (FiCO2 = 4-5%, FiCO2 = 11-12% or FiCO2 = 16-17%; FiO2 = 0.7; balance N2) was immediately administered to maintain the target PaCO2 in the NC (a PaCO2 of 35-45 mmHg), MHA (a PaCO2 of 80-100 mmHg) and SHA (a PaCO2 of 130-150 mmHg) groups. Nine normal or non-ventilated rats served as controls. The hemodynamics, gas exchange and inflammatory parameters were measured. The role of NF-κB pathway in hypercapnic acidosis-mediated protection from high-pressure stretch injury was then determined. In the NC group, high-pressure ventilation resulted in a decrease in PaO2/FiO2 from 415.6 (37.1) mmHg to 179.1 (23.5) mmHg (p < 0.001), but improved by MHA (379.9 ± 34.5 mmHg) and SHA (298.6 ± 35.3 mmHg). The lung injury score in the SHA group (7.8 ± 1.6) was lower than the NC group (11.8 ± 2.3, P < 0.05) but was higher than the MHA group (4.4 ± 1.3, P < 0.05). Compared with the NC group, after 4 h of high pressure ventilation, the MHA and SHA groups had decreases in MPO activity of 67% and 33%, respectively, and also declined the levels of TNF-α (58% versus 72%) and MIP-2 (76% versus 60%) in the BALF. Additionally, both hypercapnic acidosis groups reduced stretch-induced NF-κB activation (p < 0.05) and significantly decreased lung ICAM-1 expression (p < 0.05). Moderate hypercapnic acidosis (PaCO2 maintained at 80-100 mmHg) has a greater protective effect on high-pressure ventilation-induced inflammatory injury. The potential mechanisms may involve alterations in NF-κB activity.

[What is the contribution of Stewart's concept in acid-base disorders analysis?].

PubMed

Quintard, H; Hubert, S; Ichai, C

2007-05-01

To explain the different approaches for interpreting acid-base disorders; to develop the Stewart model which offers some advantages for the pathophysiological understanding and the clinical interpretation of acid-base imbalances. Record of french and english references from Medline data base. The keywords were: acid-base balance, hyperchloremic acidosis, metabolic acidosis, strong ion difference, strong ion gap. Data were selected including prospective and retrospective studies, reviews, and case reports. Acid-base disorders are commonly analysed by using the traditional Henderson-Hasselbalch approach which attributes the variations in plasma pH to the modifications in plasma bicarbonates or PaCO2. However, this approach seems to be inadequate because bicarbonates and PaCO2 are completely dependent. Moreover, it does not consider the role of weak acids such as albuminate, in the determination of plasma pH value. According to the Stewart concept, plasma pH results from the degree of plasma water dissociation which is determined by 3 independent variables: 1) strong ion difference (SID) which is the difference between all the strong plasma cations and anions; 2) quantity of plasma weak acids; 3) PaCO2. Thus, metabolic acid-base disorders are always induced by a variation in SID (decreased in acidosis) or in weak acids (increased in acidosis), whereas respiratory disorders remains the consequence of a change in PaCO2. These pathophysiological considerations are important to analyse complex acid-base imbalances in critically ill patients. For example, due to a decrease in weak acids, hypoalbuminemia increases SID which may counter-balance a decrease in pH and an elevated anion gap. Thus if using only traditional tools, hypoalbuminemia may mask a metabolic acidosis, because of a normal pH and a normal anion gap. In this case, the association of metabolic acidosis and alkalosis is only expressed by respectively a decreased SID and a decreased weak acids concentration. This concept allows to establish the relationship between hyperchloremic acidosis and infusion of solutes which contain large concentration of chloride such as NaCl 0.9%. Finally, the Stewart concept permits to understand that sodium bicarbonate as well as sodium lactate induces plasma alkalinization. In fact, sodium remains in plasma, whereas anion (lactate or bicarbonate) are metabolized leading to an increase in plasma SID. Due to its simplicity, the traditional Henderson-Hasselbalch approach of acid-base disorders, remains commonly used. However, it gives an inadequate pathophysiological analysis which may conduct to a false diagnosis, especially with complex acid-base imbalances. Despite its apparent complexity, the Stewart concept permits to understand precisely the mechanisms of acid-base disorders. It has to become the most appropriate approach to analyse complex acid-base abnormalities.

An Investigation into Rumen Fungal and Protozoal Diversity in Three Rumen Fractions, during High-Fiber or Grain-Induced Sub-Acute Ruminal Acidosis Conditions, with or without Active Dry Yeast Supplementation

PubMed Central

Ishaq, Suzanne L.; AlZahal, Ousama; Walker, Nicola; McBride, Brian

2017-01-01

Sub-acute ruminal acidosis (SARA) is a gastrointestinal functional disorder in livestock characterized by low rumen pH, which reduces rumen function, microbial diversity, host performance, and host immune function. Dietary management is used to prevent SARA, often with yeast supplementation as a pH buffer. Almost nothing is known about the effect of SARA or yeast supplementation on ruminal protozoal and fungal diversity, despite their roles in fiber degradation. Dairy cows were switched from a high-fiber to high-grain diet abruptly to induce SARA, with and without active dry yeast (ADY, Saccharomyces cerevisiae) supplementation, and sampled from the rumen fluid, solids, and epimural fractions to determine microbial diversity using the protozoal 18S rRNA and the fungal ITS1 genes via Illumina MiSeq sequencing. Diet-induced SARA dramatically increased the number and abundance of rare fungal taxa, even in fluid fractions where total reads were very low, and reduced protozoal diversity. SARA selected for more lactic-acid utilizing taxa, and fewer fiber-degrading taxa. ADY treatment increased fungal richness (OTUs) but not diversity (Inverse Simpson, Shannon), but increased protozoal richness and diversity in some fractions. ADY treatment itself significantly (P < 0.05) affected the abundance of numerous fungal genera as seen in the high-fiber diet: Lewia, Neocallimastix, and Phoma were increased, while Alternaria, Candida Orpinomyces, and Piromyces spp. were decreased. Likewise, for protozoa, ADY itself increased Isotricha intestinalis but decreased Entodinium furca spp. Multivariate analyses showed diet type was most significant in driving diversity, followed by yeast treatment, for AMOVA, ANOSIM, and weighted UniFrac. Diet, ADY, and location were all significant factors for fungi (PERMANOVA, P = 0.0001, P = 0.0452, P = 0.0068, Monte Carlo correction, respectively, and location was a significant factor (P = 0.001, Monte Carlo correction) for protozoa. Diet-induced SARA shifts diversity of rumen fungi and protozoa and selects against fiber-degrading species. Supplementation with ADY mitigated this reduction in protozoa, presumptively by triggering microbial diversity shifts (as seen even in the high-fiber diet) that resulted in pH stabilization. ADY did not recover the initial community structure that was seen in pre-SARA conditions. PMID:29067009

An Investigation into Rumen Fungal and Protozoal Diversity in Three Rumen Fractions, during High-Fiber or Grain-Induced Sub-Acute Ruminal Acidosis Conditions, with or without Active Dry Yeast Supplementation.

PubMed

Ishaq, Suzanne L; AlZahal, Ousama; Walker, Nicola; McBride, Brian

2017-01-01

Sub-acute ruminal acidosis (SARA) is a gastrointestinal functional disorder in livestock characterized by low rumen pH, which reduces rumen function, microbial diversity, host performance, and host immune function. Dietary management is used to prevent SARA, often with yeast supplementation as a pH buffer. Almost nothing is known about the effect of SARA or yeast supplementation on ruminal protozoal and fungal diversity, despite their roles in fiber degradation. Dairy cows were switched from a high-fiber to high-grain diet abruptly to induce SARA, with and without active dry yeast (ADY, Saccharomyces cerevisiae ) supplementation, and sampled from the rumen fluid, solids, and epimural fractions to determine microbial diversity using the protozoal 18S rRNA and the fungal ITS1 genes via Illumina MiSeq sequencing. Diet-induced SARA dramatically increased the number and abundance of rare fungal taxa, even in fluid fractions where total reads were very low, and reduced protozoal diversity. SARA selected for more lactic-acid utilizing taxa, and fewer fiber-degrading taxa. ADY treatment increased fungal richness (OTUs) but not diversity (Inverse Simpson, Shannon), but increased protozoal richness and diversity in some fractions. ADY treatment itself significantly ( P < 0.05) affected the abundance of numerous fungal genera as seen in the high-fiber diet: Lewia, Neocallimastix , and Phoma were increased, while Alternaria, Candida Orpinomyces , and Piromyces spp. were decreased. Likewise, for protozoa, ADY itself increased Isotricha intestinalis but decreased Entodinium furca spp. Multivariate analyses showed diet type was most significant in driving diversity, followed by yeast treatment, for AMOVA, ANOSIM, and weighted UniFrac. Diet, ADY, and location were all significant factors for fungi (PERMANOVA, P = 0.0001, P = 0.0452, P = 0.0068, Monte Carlo correction, respectively, and location was a significant factor ( P = 0.001, Monte Carlo correction) for protozoa. Diet-induced SARA shifts diversity of rumen fungi and protozoa and selects against fiber-degrading species. Supplementation with ADY mitigated this reduction in protozoa, presumptively by triggering microbial diversity shifts (as seen even in the high-fiber diet) that resulted in pH stabilization. ADY did not recover the initial community structure that was seen in pre-SARA conditions.

Impact of acute metabolic acidosis on the acid-base balance in follicular fluid and blood in dairy cattle.

PubMed

Indrova, E; Dolezel, R; Novakova-Mala, J; Pechova, A; Zavadilova, M; Cech, S

2017-02-01

Acid-base balance is one of the most vigorously regulated variables of the body, including genital organs. Subacute ruminal acidosis is a common disturbance in dairy cows that disturbs several biochemical indices in the blood, cerebrospinal fluid, and urine. The possible negative effects of metabolic acidosis on the follicular fluid (FF) composition and, subsequently, on oocyte quality, are not fully elucidated. This study aimed to evaluate the changes in acid-base balance (ABB) in FF and blood during acute metabolic acidosis in dairy heifers. Ten Holstein heifers were stimulated with FSH in eight decreasing doses at 12-hour intervals (D0-D3). Acidosis was induced by oral administration of sucrose at 9 g/kg of body weight, dissolved in 10 L of warm tap water, at D3. Samples were collected from each cow at 0, 8, 12, 16, 24, 32, 40, and 48 hours after treatment. Samples of FF, obtained by transvaginal follicular aspiration, and peripheral blood were examined for ABB parameters: pH, pCO 2 , pO 2 , HCO 3 - , and base excess (BE). A significant decrease in pH, HCO 3 - , and BE values in the blood, as well as FF, occurred after sucrose treatment. The lowest pH values occurred in blood at 16 hours, and in FF at 24 hours, after treatment (7.30 ± 0.05 and 7.33 ± 0.05, respectively). The lowest HCO 3 - values in blood (18.75 ± 3.2 mmol/L) and FF (18.07 ± 2.84 mmol/L) occurred 24 hours after treatment, as did the lowest BE values (-6.61 ± 3.7 mmol/L and -7.53 ± 3.89 mmol/L, in blood and FF, respectively). Significant correlations for HCO 3 - (r = 0.928), BE (r = 0.946), pH (r = 0.889), and pCO 2 (r = 0.522) existed between blood and FF samples. The results demonstrated that metabolic acute acidosis substantially influences the characteristics of both serum and FF. Copyright © 2016 Elsevier Inc. All rights reserved.

The relationship between rumen acidosis resistance and expression of genes involved in regulation of intracellular pH and butyrate metabolism of ruminal epithelial cells in steers.

PubMed

Schlau, N; Guan, L L; Oba, M

2012-10-01

Past research has focused on the prevention and management of subacute rumen acidosis by manipulating the ration; however, the severity of acidosis varies even among animals fed a common high-grain diet. The objectives of this study were to compare the ruminal volatile fatty acid (VFA) profile and expression of genes involved in the metabolism of butyrate, the VFA most extensively metabolized by the ruminal epithelium, and intracellular pH regulation in ruminal epithelial cells between acidosis-resistant (AR) and acidosis-susceptible (AS) steers. Acidosis indexes (area per day under pH 5.8 divided by dry matter intake) were measured for 17 steers fed a common high-grain diet, and the 3 steers with the lowest (1.4 ± 1.2 pH∙min/kg) and the 3 with the highest values (23.9 ± 7.4 pH∙min/kg) were classified as AR and AS, respectively, and used in the subsequent study. The steers were force-fed a diet containing 85% grain at 60% of the expected daily intake (5.8 ± 0.8 and 5.6 ± 0.6 kg for AR and AS, respectively) within 30 min. Mean ruminal pH over the postprandial 6-h period was higher for AR compared with AS (6.02 vs. 5.55), and mean total VFA concentration was 74% for AR compared with AS (122 vs. 164 mM). Molar proportion of butyrate in the ruminal fluid was 139% higher for AR compared with AS (17.5 vs. 7.33 mol/100 mol of VFA). Expression of monocarboxylate cotransporter isoform 1, sodium hydrogen exchanger isoforms 1 and 2, and anion exchangers (downregulated in adenoma and putative anion exchanger, isoform 1) did not differ between AR and AS steers. However, expression of sodium hydrogen exchanger isoform 3, which imports Na(+) to the epithelial cell and exports H(+) to the rumen, was 176% higher in AR steers than in AS steers. Higher ruminal pH for AR might be partly due to a faster rate of VFA absorption, lower VFA production, or both. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.