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

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.

Chronic acetaminophen ingestion resulting in severe anion gap metabolic acidosis secondary to 5-oxoproline accumulation: an under diagnosed phenomenon.

PubMed

O'Brien, L Morgan Nordstrom; Hooper, Michael; Flemmer, Mark; Marik, Paul Ellis

2012-07-03

Anion gap metabolic acidosis is commonly caused by lactic acidosis, ketoacidosis, and ingestion of methanol, salicylates, ethylene glycol or accumulation of organic/inorganic acids. However, rare causes of metabolic acidosis from enzyme defects, such as disturbances in the γ-glutamyl cycle, are being reported in higher frequencies in the adult population. Such disturbances cause an accumulation of 5-oxoproline and ultimately an anion gap metabolic acidosis. These disturbances are often associated with acetaminophen in the setting of certain risk factors such as sepsis, malnutrition, liver disease, female gender, pregnancy or renal failure.

Chronic acetaminophen ingestion resulting in severe anion gap metabolic acidosis secondary to 5-oxoproline accumulation: an under diagnosed phenomenon

PubMed Central

O’Brien, L. Morgan Nordstrom; Hooper, Michael; Flemmer, Mark; Marik, Paul Ellis

2012-01-01

Anion gap metabolic acidosis is commonly caused by lactic acidosis, ketoacidosis, and ingestion of methanol, salicylates, ethylene glycol or accumulation of organic/inorganic acids. However, rare causes of metabolic acidosis from enzyme defects, such as disturbances in the γ-glutamyl cycle, are being reported in higher frequencies in the adult population. Such disturbances cause an accumulation of 5-oxoproline and ultimately an anion gap metabolic acidosis. These disturbances are often associated with acetaminophen in the setting of certain risk factors such as sepsis, malnutrition, liver disease, female gender, pregnancy or renal failure. PMID:22761219

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.

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.

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.

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

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

[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.

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.

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.

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 �

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.

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

[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.

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

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.

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.

[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.

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.

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.

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.

Metabolic acidosis and 5-oxoprolinuria induced by flucloxacillin and acetaminophen: a case report.

PubMed

Lanoy, Charlotte; Bouckaert, Yves

2016-06-23

Frequent causes of high anion gap metabolic acidosis are well known: ethanol, methanol, and ethylene glycol intoxication; hyperglycemia; lactic or D-lactic acidosis; and impaired renal function. There are other causes, less frequent but also important. This report illustrates a rare case of a patient with increased anion gap metabolic acidosis due to a deficit of the γ-glutamyl cycle that led to 5-oxoproline (acid pyroglutamic) accumulation. An 82-year-old white woman was admitted to our intensive care unit because of septic shock caused by right knee methicillin-sensitive Staphylococcus aureus-induced arthritis. She was treated for 10 days with flucloxacillin and rifampicin and developed metabolic acidosis with high anion gap. Her test results for methanol, ethanol, ethylene glycol, and acetylsalicylic acid were negative. Her glycemia, lactate level, and renal function were normal. However, the result of a urinary assay for pyroglutamate was positive. We concluded that the patient had metabolic acidosis induced by accumulation of 5-oxoproline. We modified her antibiotic treatment, administered acetylcysteine, and her acidosis resolved. 5-Oxoprolinuria (pyroglutamic acid accumulation) is a rare, probably underdiagnosed cause of transient metabolic acidosis with increased anion gap.

Metabolic acidosis mimicking diabetic ketoacidosis after use of calorie-free mineral water.

PubMed

Dahl, Gry T; Woldseth, Berit; Lindemann, Rolf

2012-09-01

A previously healthy boy was admitted with fever, tachycardia, dyspnea, and was vomiting. A blood test showed a severe metabolic acidosis with pH 7.08 and an anion gap of 36 mmol/L. His urine had an odor of acetone. The serum glucose was 5.6 mmol/L, and no glucosuria was found. Diabetic ketoacidosis could therefore be eliminated. Lactate level was normal. Tests for the most common metabolic diseases were negative. Because of herpes stomatitis, the boy had lost appetite and only been drinking Diet Coke and water the last days. Diet Coke or Coca-Cola Light is sweetened with a blend containing cyclamates, aspartame, and acesulfame potassium, all free of calories. The etiology of the metabolic acidosis appeared to be a catabolic situation exaggerated by fasting with no intake of calories. The elevated anion gap was due to a severe starvation ketoacidosis, mimicking a diabetic ketoacidosis. Pediatricians should recommend carbohydrate/calorie-containing fluids for rehydration of children with acute fever, diarrhea, or illness.

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.

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.

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.

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.

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.

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

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.

Respiratory alkalosis and metabolic acidosis in a child treated with sulthiame.

PubMed

Weissbach, Avichai; Tirosh, Irit; Scheuerman, Oded; Hoffer, Vered; Garty, Ben Zion

2010-10-01

To report on severe acid-base disturbance in a child with symptomatic epilepsy treated with sulthiame. A 9.5-year-old boy with chronic generalized tonic-clonic seizures was treated with carbamazepine and valproic acid. Because of poor seizure control, sulthiame was added to the treatment. Two months later, he presented at the emergency department with severe weakness, headache, dizziness, dyspnea, anorexia, and confusional state. Arterial blood gas analysis showed mixed respiratory alkalosis with high anion gap metabolic acidosis. Sulthiame-induced acid-base disturbance was suspected. The drug was withheld for the first 24 hours and then restarted at a reduced dosage. The arterial blood gases gradually normalized, the confusion disappeared, and the patient was discharged home.Three months later, 4 weeks after an increase in sulthiame dosage, the patient was once again admitted with the same clinical picture. Improvement was noted after the drug dosage was reduced. This is the first report of mixed respiratory alkalosis and metabolic acidosis in a child treated with sulthiame. Monitoring of the acid-base status should be considered in patients treated with sulthiame.

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.

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

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

Pyroglutamic acid-induced metabolic acidosis: a case report.

PubMed

Luyasu, S; Wamelink, M M C; Galanti, L; Dive, A

2014-06-01

High anion gap metabolic acidosis due to pyroglutamic acid (5-oxoproline) is a rare complication of acetaminophen treatment (which depletes glutathione stores) and is often associated with clinically moderate to severe encephalopathy. Acquired 5-oxoprolinase deficiency (penicillins) or the presence of other risk factors of glutathione depletion such as malnutrition or sepsis seems to be necessary for symptoms development. We report the case of a 55-year-old women who developed a symptomatic overproduction of 5-oxoproline during flucloxacillin treatment for severe sepsis while receiving acetaminophen for fever control. Hemodialysis accelerated the clearance of the accumulated organic acid, and was followed by a sustained clinical improvement.

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.

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.

Pyroglutamic acidemia: a cause of high anion gap metabolic acidosis.

PubMed

Dempsey, G A; Lyall, H J; Corke, C F; Scheinkestel, C D

2000-06-01

To report four cases of pyroglutamic acidemia in adults causing clinically significant acidosis. Patients admitted to the intensive care units of the Alfred Hospital (a quaternary referral center) and Geelong Hospital (a major regional center) with an unexplained high anion gap acidosis. Pyroglutamic acidemia (5-oxoprolinemia) is a rare cause of high anion gap metabolic acidosis that should be suspected in patients presenting with sepsis, hepatic, and/or renal dysfunction who are receiving drugs such as acetaminophen, flucloxacillin, and vigabatrin after the more common causes of a high anion gap acidosis have been excluded. Should pyroglutamic aciduria be present, known precipitants should be ceased, infection should be managed aggressively, and supportive management should be instituted.

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.

Respiratory and metabolic acidosis differentially affect the respiratory neuronal network in the ventral medulla of neonatal rats.

PubMed

Okada, Yasumasa; Masumiya, Haruko; Tamura, Yoshiyasu; Oku, Yoshitaka

2007-11-01

Two respiratory-related areas, the para-facial respiratory group/retrotrapezoid nucleus (pFRG/RTN) and the pre-Bötzinger complex/ventral respiratory group (preBötC/VRG), are thought to play key roles in respiratory rhythm. Because respiratory output patterns in response to respiratory and metabolic acidosis differ, we hypothesized that the responses of the medullary respiratory neuronal network to respiratory and metabolic acidosis are different. To test these hypotheses, we analysed respiratory-related activity in the pFRG/RTN and preBötC/VRG of the neonatal rat brainstem-spinal cord in vitro by optical imaging using a voltage-sensitive dye, and compared the effects of respiratory and metabolic acidosis on these two populations. We found that the spatiotemporal responses of respiratory-related regional activities to respiratory and metabolic acidosis are fundamentally different, although both acidosis similarly augmented respiratory output by increasing respiratory frequency. PreBötC/VRG activity, which is mainly inspiratory, was augmented by respiratory acidosis. Respiratory-modulated pixels increased in the preBötC/VRG area in response to respiratory acidosis. Metabolic acidosis shifted the respiratory phase in the pFRG/RTN; the pre-inspiratory dominant pattern shifted to inspiratory dominant. The responses of the pFRG/RTN activity to respiratory and metabolic acidosis are complex, and involve either augmentation or reduction in the size of respiratory-related areas. Furthermore, the activation pattern in the pFRG/RTN switched bi-directionally between pre-inspiratory/inspiratory and post-inspiratory. Electrophysiological study supported the results of our optical imaging study. We conclude that respiratory and metabolic acidosis differentially affect activities of the pFRG/RTN and preBötC/VRG, inducing switching and shifts of the respiratory phase. We suggest that they differently influence the coupling states between the pFRG/RTN and preBötC/VRG.

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.

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.

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.

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.

Severe lactic acidosis after an iatrogenic propylene glycol overdose.

PubMed

Zosel, Amy; Egelhoff, Elizabeth; Heard, Kennon

2010-02-01

Propylene glycol is a diluent found in many intravenous and oral drugs, including phenytoin, diazepam, and lorazepam. Propylene glycol is eliminated from the body by oxidation through alcohol dehydrogenase to form lactic acid. Under normal conditions, the body converts lactate to pyruvate and metabolizes pyruvate through the Krebs cycle. Lactic acidosis has occurred in patients, often those with renal dysfunction, who were receiving prolonged infusions of drugs that contain propylene glycol as a diluent. We describe a 50-year-old man who experienced severe lactic acidosis after receiving an accidental overdose of lorazepam, which contains propylene glycol. The patient was acutely intoxicated, with a serum ethanol concentration of 406 mg/dl. He had choked on a large piece of meat and subsequently experienced pulseless electrical activity with ventricular fibrillation cardiac arrest. He was brought to the emergency department; within 2 hours, he was admitted to the intensive care unit for initiation of the hypothermia protocol. The patient began to experience generalized tonic-clonic seizures 12 hours later, which resolved after several boluses of lorazepam. A lorazepam infusion was started; however, it was inadvertently administered at a rate of 2 mg/minute instead of the standard rate of 2 mg/hour. Ten hours later, the administration error was recognized and the infusion stopped. The patient's peak propylene glycol level was 659 mg/dl, pH 6.9, serum bicarbonate level 5 mEq/L, and lactate level 18.6 mmol/L. Fomepizole was started the next day and was continued until hospital day 3. Continuous renal replacement therapy was started and then replaced with continuous venovenous hemofiltration (CVVH) for the remainder of the hospital stay. The patient's acidosis resolved by day 3, when his propylene glycol level had decreased to 45 mg/dl. Fomepizole was discontinued, but the patient's prognosis was poor (anoxic brain injury); thus care was withdrawn and the patient died

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.

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.

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.

Nephrolithiasis in renal tubular acidosis.

PubMed

Buckalew, V M

1989-03-01

Renal tubular acidosis is a term applied to several conditions in which metabolic acidosis is caused by specific defects in renal tubular hydrogen ion secretion. Three types of renal tubular acidosis generally are recognized based on the nature of the tubular defect. Nephrolithiasis occurs only in type I renal tubular acidosis, a condition marked by an abnormality in the generation and maintenance of a hydrogen ion gradient by the distal tubule. A forme fruste of type I renal tubular acidosis has been described in which the characteristic defect in distal hydrogen ion secretion occurs in the absence of metabolic acidosis (incomplete renal tubular acidosis). Type I renal tubular acidosis is a heterogeneous disorder that may be hereditary, idiopathic or secondary to a variety of conditions. Secondary type I renal tubular acidosis in sporadic cases is associated most commonly with autoimmune diseases, such as Sjögren's syndrome and systemic lupus erythematosus, and it occurs more frequently in women than men. Nephrolithiasis, which may occur in any of the subsets of type I renal tubular acidosis, accounts for most of the morbidity in adults and adolescents. Major risk factors for nephrolithiasis include alkaline urine, hypercalciuria and hypocitraturia. In addition, we found hyperuricosuria in 21 per cent of the patients with type I renal tubular acidosis with nephrolithiasis. The most frequently occurring risk factor, hypocitraturia, is due to decreased filtered load and/or to increased tubular reabsorption of filtered citrate. While increased tubular reabsorption may be due to systemic acidosis, hypocitraturia occurs in incomplete renal tubular acidosis. Furthermore, alkali therapy (either bicarbonate or citrate salts) increases citrate excretion in complete and incomplete type I renal tubular acidosis. These data suggest that hypocitraturia in type I renal tubular acidosis may be due to a defect in proximal tubule function. Hypercalciuria appears to have 2 causes

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

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.

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.

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

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.

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

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

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

[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.

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.

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

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.

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.

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

D-Lactic Acidosis in Humans: Review of Update

PubMed Central

Kang, Kyung Pyo; Lee, Sik

2006-01-01

D-Lactic acidosis has been well documented in ruminants. In humans, D-lactic acidosis is very rare, but D-lactic acidosis may be more common than generally believed and should be looked for in a case of metabolic acidosis in which the cause of acidosis is not apparent. The clinical presentation of D-lactic acidosis is characterized by episodes of encephalopathy and metabolic acidosis. The entity should be considered as a diagnosis in a patient who presents with metabolic acidosis accompanied by high anion gap, normal lactate level, negative Acetest, history of short bowel syndrome or malabsorption, and characteristic neurologic manifestations. Low carbohydrate diet, bicarbonate treatment, rehydration, and oral antibiotics would be helpful in controlling symptoms. PMID:24459486

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.

Metabolic acidosis status and mortality in patients on the end stage of renal disease.

PubMed

Raikou, Vaia D

2016-12-01

Uncorrected metabolic acidosis leads to higher death risk in dialysis patients. We observed the relationship between metabolic acidosis status and mortality rate in patients on renal replacement therapy during a median follow up time of 60 months. We studied 76 patients on an on-line hemodiafiltration. The dialysis adequacy was defined by Kt/V for urea. The Framingham risk score (FRS) points were used to determine the 10-year risk for coronary heart disease. We examined the impact of high or low serum bicarbonate concentrations on mortality rate and on 10-year risk for coronary heart disease via the Kaplan-Meier method. Cox's model was used to evaluate a combination of prognostic variables, such as dialysis adequacy defined by Kt/V for urea, age and serum bicarbonate concentrations. We divided the enrolled patients in three groups according to serum bicarbonate concentrations (< 20 mmol/L, 20-22 mmol/L and > 22 mmol/L). Kaplan-Meier survival curve for the impact of serum bicarbonate concentrations on overall mortality was found significant (log-rank = 7.8, P = 0.02). The prevalence of serum bicarbonate less or more than 20 mmol/L on high FRS (> 20%) by Kaplan-Meier curve was also found significant (log-rank = 4.9, P = 0.02). Cox's model revealed the significant predictive effect of serum bicarbonate on overall mortality ( P = 0.006, OR = 1.5, 95% CI = 1.12-1.98) in combination to Kt/V for urea and age. Uncorrected severe metabolic acidosis, defined by serum bicarbonate concentrations less than 20 mmol/L, is associated with a 10-year risk for coronary heart disease more than 20% and high overall mortality in patients on renal replacement therapy.

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

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

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

Lactic Acidosis in a Patient with Type 2 Diabetes Mellitus

PubMed Central

2015-01-01

Lactic acidosis occurs when lactate production exceeds its metabolism. There are many possible causes of lactic acidosis, and in any given patient, several causes may coexist. This Attending Rounds presents a case in point. Metformin’s role in the pathogenesis of lactic acidosis in patients with diabetes mellitus is complex, as the present case illustrates. The treatment of lactic acidosis is controversial, except for the imperative to remedy its underlying cause. The use of sodium bicarbonate to treat the often alarming metabolic derangements may be quite efficacious in that regard but is of questionable benefit to patients. Renal replacement therapies (RRTs) have particular appeal in this setting for a variety of reasons, but their effect on clinical outcomes is untested. PMID:25762524

5-Oxoproline as a cause of high anion gap metabolic acidosis: an uncommon cause with common risk factors.

PubMed

Kortmann, W; van Agtmael, M A; van Diessen, J; Kanen, B L J; Jakobs, C; Nanayakkara, P W B

2008-09-01

High anion gap metabolic acidosis might be caused by 5-oxoproline (pyroglutamic acid). As it is very easy to treat, it might be worth drawing attention to this uncommon and probably often overlooked diagnosis. We present three cases of high anion gap metabolic acidosis due to 5-oxoproline seen within a period of six months.

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

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.

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.

Lactic Acidosis in a Patient with Type 2 Diabetes Mellitus.

PubMed

Weisberg, Lawrence S

2015-08-07

Lactic acidosis occurs when lactate production exceeds its metabolism. There are many possible causes of lactic acidosis, and in any given patient, several causes may coexist. This Attending Rounds presents a case in point. Metformin's role in the pathogenesis of lactic acidosis in patients with diabetes mellitus is complex, as the present case illustrates. The treatment of lactic acidosis is controversial, except for the imperative to remedy its underlying cause. The use of sodium bicarbonate to treat the often alarming metabolic derangements may be quite efficacious in that regard but is of questionable benefit to patients. Renal replacement therapies (RRTs) have particular appeal in this setting for a variety of reasons, but their effect on clinical outcomes is untested. Copyright © 2015 by the American Society of Nephrology.

Prolonged resuscitation of metabolic acidosis after trauma is associated with more complications.

PubMed

Weinberg, Douglas S; Narayanan, Arvind S; Moore, Timothy A; Vallier, Heather A

2015-09-24

Optimal patterns for fluid management are controversial in the resuscitation of major trauma. Similarly, appropriate surgical timing is often unclear in orthopedic polytrauma. Early appropriate care (EAC) has recently been introduced as an objective model to determine readiness for surgery based on the resuscitation of metabolic acidosis. EAC is an objective treatment algorithm that recommends fracture fixation within 36 h when either lactate <4.0 mmol/L, pH ≥ 7.25, or base excess (BE) ≥-5.5 mmol/L. The aim of this study is to better characterize the relationship between post-operative complications and the time required for resuscitation of metabolic acidosis using EAC. At an adult level 1 trauma center, 332 patients with major trauma (Injury Severity Score (ISS) ≥16) were prospectively treated with EAC. The time from injury to EAC resuscitation was determined in all patients. Age, race, gender, ISS, American Society of Anesthesiologists score (ASA), body mass index (BMI), outside hospital transfer status, number of fractures, and the specific fractures were also reviewed. Complications in the 6-month post-operative period were adjudicated by an independent multidisciplinary committee of trauma physicians and included infection, sepsis, pulmonary embolism, deep venous thrombosis, renal failure, multiorgan failure, pneumonia, and acute respiratory distress syndrome. Univariate analysis and binomial logistic regression analysis were used to compare complications between groups. Sixty-six patients developed complications, which was less than a historical cohort of 1,441 patients (19.9% vs. 22.1%). ISS (p < 0.0005) and time to EAC resuscitation (p = 0.041) were independent predictors of complication rate. A 2.7-h increase in time to resuscitation had odds for sustaining a complication equivalent to a 1-unit increase on the ISS. EAC guidelines were safe, effective, and practically implemented in a level 1 trauma center. During the resuscitation course

[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.

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

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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

Hyperosmolar metabolic acidosis in burn patients exposed to glycol based topical antimicrobials-A systematic review.

PubMed

Leibson, Tom; Davies, Paige; Nickel, Cheri; Koren, Gideon

2018-06-01

The well documented susceptibility of burn patients to acquired infections via damaged skin mandates application of antimicrobial agents. These agents are dissolved in various vehicles that augment skin absorption thus allowing greater efficacy. Polyethylene glycol (PEG) and Propylene glycol (PropG) are among the most commonly used vehicles, and both have been used in numerous medications and cosmetic products over the past few decades. Rarely, burn patients treated with agents containing these glycols present with a life threatening systemic toxidrome of hyperosmolar metabolic acidosis. We present a systematic review of outcomes in burn patients treated with similar agents. Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters), from database inception to August 4th, 2016. All publications of clinical burn patient studies included at least one arm receiving a glycol based topical therapy. A total of 61 studies involving 10,282 patients and 4 different antimicrobial medications fulfilled the inclusion criteria. Nine burn patients (0.09%) were documented to present with hyperosmolar metabolic acidosis during topical silver sulfadiazine treatment. Propylene glycol isolated from their blood accounted for the high osmole gap. This first systematic review found very few cases of documented hyperosmolar metabolic acidosis, all within one study that had set to specifically explore this toxidrome. High index of suspicion with frequent osmolar gap monitoring may help identify future toxicities in a timely manner. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

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.

Guilty as charged: unmeasured urinary anions in a case of pyroglutamic acidosis.

PubMed

Rolleman, E J; Hoorn, E J; Didden, P; Zietse, R

2008-09-01

A patient developed an unexplained metabolic acidosis with the characteristics of renal tubular acidosis. By correcting the serum anion gap for hypoalbuminaemia and analysing the urinary anions and cations, the presence of unmeasured anions was revealed. The diagnosis of pyroglutamic acidosis, caused by a combination of flucloxacillin and acetaminophen, was established. Strategies for solving complex cases of metabolic acidosis are discussed.

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

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

Severe metabolic alkalosis, hypokalemia, and respiratory acidosis induced by the Chinese herbal medicine yokukansan in an elderly patient with muscle weakness and drowsiness.

PubMed

Yamada, Shunsuke; Tokumoto, Masanori; Kansui, Yasuo; Wakisaka, Yoshinobu; Uchizono, Yuji; Tsuruya, Kazuhiko; Ooboshi, Hiroaki

2013-05-01

Yokukansan is a Chinese herbal medicine containing licorice that has been shown to alleviate the behavioral and psychological symptoms of Alzheimer's disease, with few adverse effects. Increasing numbers of patients with Alzheimer's disease in Japan are now being treated with this drug. However, yokukansan should be used with caution because of its potential to induce pseudoaldosteronism through the inhibition of 11-beta-hydroxysteroid dehydrogenase type 2, which metabolizes cortisol into cortisone. We present the case of an 88-year-old woman with a history of Alzheimer's disease who was transferred to our emergency department because of drowsiness, anorexia, and muscle weakness. Her blood pressure was 168/90 mmHg. Laboratory data showed serum potassium of 1.9 mmol/l, metabolic alkalosis (pH 7.54; HCO 3 - , 50.5 mmol/l; chloride, 81 mmol/l; sodium, 140 mmol/l), and respiratory disorders (pCO 2 , 60.5 mmHg; pO 2 , 63.8 mmHg). Plasma renin activity and aldosterone concentration were suppressed, and urinary potassium excretion was 22 mmol/l (calculated transtubular potassium gradient 12.9). An electrocardiogram showed flat T-waves and U-waves with ventricular premature contractions. Echocardiography denied volume depletion. Medical interview disclosed that she had been treated with a Chinese herbal medicine (yokukansan) containing licorice. The final diagnosis was pseudoaldosteronism and respiratory acidosis induced by licorice. Hypokalemia, metabolic alkalosis, and respiratory acidosis all subsided shortly after the discontinuation of yokukansan and initiation of intravenous potassium replacement. This case highlights the need for nephrologists to consider the possible involvement of Chinese herbal medicines, including yokukansan, when they encounter hypokalemia in elderly patients.

[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.

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.

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

Endocrine and metabolic emergencies in children: hypocalcemia, hypoglycemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis

PubMed Central

2015-01-01

It is important to fast diagnosis and management of the pediatric patients of the endocrine metabolic emergencies because the signs and symptoms of these disorders are nonspecific. Delayed diagnosis and treatment may lead to serious consequences of the pediatric patients, for example, cerebral dysfunction leading to coma or death of the patients with hypoglycemia, hypocalcemia, adrenal insufficiency, or diabetic ketoacidosis. The index of suspicion of the endocrine metabolic emergencies should be preceded prior to the starting nonspecific treatment. Importantly, proper diagnosis depends on the collection of blood and urine specimen before nonspecific therapy (intravenous hydration, electrolytes, glucose or calcium injection). At the same time, the taking of precise history and searching for pathognomonic physical findings should be performed. This review was described for fast diagnosis and proper management of hypoglycemic emergencies, hypocalcemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis. PMID:26817004

Successfully Treated Calcific Uremic Arteriolopathy: Two Cases of a High Anion Gap Metabolic Acidosis with Intravenous Sodium Thiosulfate

PubMed Central

Rein, Joshua L.; Miyata, Kana N.; Dadzie, Kobena A.; Gruber, Steven J.; Sulica, Roxana; Winchester, James F.

2014-01-01

Calcific uremic arteriolopathy (CUA) is a rare and potentially fatal disorder of calcification involving subcutaneous small vessels and fat in patients with renal insufficiency. We describe the successful use of intravenous sodium thiosulfate (STS) for the treatment of CUA in two patients. The first case was complicated by the development of a severe anion gap metabolic acidosis, which was accompanied by a seizure. Both patients had complete wound healing within five months. Although STS should be considered in the treatment of CUA, little is known about pharmacokinetics and additional studies are required to determine dosing strategies to minimize severe potential side effects. PMID:25506005

[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.

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.

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.

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.

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

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.

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.

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.

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.

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.

Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality.

PubMed

Starke, Astrid; Corsenca, Alf; Kohler, Thomas; Knubben, Johannes; Kraenzlin, Marius; Uebelhart, Daniel; Wüthrich, Rudolf P; von Rechenberg, Brigitte; Müller, Ralph; Ambühl, Patrice M

2012-09-01

Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate. This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] <24 mmol/L) undergoing treatment with either potassium citrate to maintain S-[HCO(3)(-)] >24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group. Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry. Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

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.

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

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.

Glucocorticoid activity and metabolism with NaCl-induced low-grade metabolic acidosis and oral alkalization: results of two randomized controlled trials.

PubMed

Buehlmeier, Judith; Remer, Thomas; Frings-Meuthen, Petra; Maser-Gluth, Christiane; Heer, Martina

2016-04-01

Low-grade metabolic acidosis (LGMA), as induced by high dietary acid load or sodium chloride (NaCl) intake, has been shown to increase bone and protein catabolism. Underlying mechanisms are not fully understood, but from clinical metabolic acidosis interactions of acid-base balance with glucocorticoid (GC) metabolism are known. We aimed to investigate GC activity/metabolism under alkaline supplementation and NaCl-induced LGMA. Eight young, healthy, normal-weight men participated in two crossover designed interventional studies. In Study A, two 10-day high NaCl diet (32 g/d) periods were conducted, one supplemented with 90 mmol KHCO3/day. In Study B, participants received a high and a low NaCl diet (31 vs. 3 g/day), each for 14 days. During low NaCl, the diet was moderately acidified by replacement of a bicarbonate-rich mineral water (consumed during high NaCl) with a non-alkalizing drinking water. In repeatedly collected 24-h urine samples, potentially bioactive-free GCs (urinary-free cortisol + free cortisone) were analyzed, as well as tetrahydrocortisol (THF), 5α-THF, and tetrahydrocortisone (THE). With supplementation of 90 mmol KHCO3, the marker of total adrenal GC secretion (THF + 5α-THF + THE) dropped (p = 0.047) and potentially bioactive-free GCs were reduced (p = 0.003). In Study B, however, GC secretion and potentially bioactive-free GCs did not exhibit the expected fall with NaCl-reduction as net acid excretion was raised by 30 mEq/d. Diet-induced acidification/alkalization affects GC activity and metabolism, which in case of long-term ingestion of habitually acidifying western diets may constitute an independent risk factor for bone degradation and cardiometabolic diseases.

A Comparison of Treating Metabolic Acidosis in CKD Stage 4 Hypertensive Kidney Disease with Fruits and Vegetables or Sodium Bicarbonate

PubMed Central

Goraya, Nimrit; Simoni, Jan; Jo, Chan-Hee

2013-01-01

Summary Background and objectives Current guidelines recommend Na+-based alkali for CKD with metabolic acidosis and plasma total CO2 (PTCO2) < 22 mM. Because diets in industrialized societies are typically acid-producing, we compared base-producing fruits and vegetables with oral NaHCO3 (HCO3) regarding the primary outcome of follow-up estimated GFR (eGFR) and secondary outcomes of improved metabolic acidosis and reduced urine indices of kidney injury. Design, setting, participants, & measurements Individuals with stage 4 (eGFR, 15–29 ml/min per 1.73 m2) CKD due to hypertensive nephropathy, had a PTCO2 level < 22 mM, and were receiving angiotensin-converting enzyme inhibition were randomly assigned to 1 year of daily oral NaHCO3 at 1.0 mEq/kg per day (n=35) or fruits and vegetables dosed to reduce dietary acid by half (n=36). Results Plasma cystatin C–calculated eGFR did not differ at baseline and 1 year between groups. One-year PTCO2 was higher than baseline in the HCO3 group (21.2±1.3 versus 19.5±1.5 mM; P<0.01) and the fruits and vegetables group (19.9±1.7 versus 19.3±1.9 mM; P<0.01), consistent with improved metabolic acidosis, and was higher in the HCO3 than the fruits and vegetable group (P<0.001). One-year urine indices of kidney injury were lower than baseline in both groups. Plasma [K+] did not increase in either group. Conclusions One year of fruits and vegetables or NaHCO3 in individuals with stage 4 CKD yielded eGFR that was not different, was associated with higher-than-baseline PTCO2, and was associated with lower-than-baseline urine indices of kidney injury. The data indicate that fruits and vegetables improve metabolic acidosis and reduce kidney injury in stage 4 CKD without producing hyperkalemia. PMID:23393104

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

Plasma first resuscitation reduces lactate acidosis, enhances redox homeostasis, amino acid and purine catabolism in a rat model of profound hemorrhagic shock

PubMed Central

D’Alessandro, Angelo; Moore, Hunter B; Moore, Ernest E; Wither, Matthew J.; Nemkov, Travis; Morton, Alexander P; Gonzalez, Eduardo; Chapman, Michael P; Fragoso, Miguel; Slaughter, Anne; Sauaia, Angela; Silliman, Christopher C; Hansen, Kirk C; Banerjee, Anirban

2016-01-01

The use of aggressive crystalloid resuscitation to treat hypoxemia, hypovolemia and nutrient deprivation promoted by massive blood loss may lead to the development of the blood vicious cycle of acidosis, hypothermia, and coagulopathy and, utterly, death. Metabolic acidosis is one of the many metabolic derangements triggered by severe trauma/hemorrhagic shock, also including enhanced proteolysis, lipid mobilization, as well as traumatic diabetes. Appreciation of the metabolic benefit of plasma first resuscitation is an important concept. Plasma resuscitation has been shown to correct hyperfibrinolysis secondary to severe hemorrhage better than normal saline. Here we hypothesize that plasma first resuscitation corrects metabolic derangements promoted by severe hemorrhage better than resuscitation with normal saline. Ultra-high-performance liquid chromatography-mass spectrometry-based metabolomics analyses were performed to screen plasma metabolic profiles upon shock and resuscitation with either platelet-free plasma or normal saline in a rat model of severe hemorrhage. Of the 251 metabolites that were monitored, 101 were significantly different in plasma vs normal saline resuscitated rats. Plasma resuscitation corrected lactate acidosis by promoting glutamine/amino acid catabolism and purine salvage reactions. Plasma first resuscitation may benefit critically injured trauma patients by relieving the lactate burden and promoting other non-clinically measured metabolic changes. In the light of our results, we propose that plasma resuscitation may promote fueling of mitochondrial metabolism, through the enhancement of glutaminolysis/amino acid catabolism and purine salvage reactions. The treatment of trauma patients in hemorrhagic shock with plasma first resuscitation is likely not only to improve coagulation, but also to promote substrate-specific metabolic corrections. PMID:26863033

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.

Acidosis, but Not Alkalosis, Affects Anaerobic Metabolism and Performance in a 4-km Time Trial.

PubMed

Correia-Oliveira, Carlos Rafaell; Lopes-Silva, João Paulo; Bertuzzi, Romulo; McConell, Glenn K; Bishop, David John; Lima-Silva, Adriano Eduardo; Kiss, Maria Augusta Peduti Dal'molin

2017-09-01

This study aimed to determine the effect of preexercise metabolic acidosis and alkalosis on power output (PO) and aerobic and anaerobic energy expenditure during a 4-km cycling time trial (TT). Eleven recreationally trained cyclists (V˙O2peak 54.1 ± 9.3 mL·kg·min) performed a 4-km TT 100 min after ingesting in a double-blind matter 0.15 g·kg of body mass of ammonium chloride (NH4Cl, acidosis), 0.3 g·kg of sodium bicarbonate (NaHCO3, alkalosis), or 0.15 g·kg of CaCO3 (placebo). A preliminary study (n = 7) was conducted to establish the optimal doses to promote the desirable preexercise blood pH alterations without gastrointestinal distress. Data for PO, aerobic and anaerobic energy expenditure, and blood and respiratory parameters were averaged for each 1 km and compared between conditions using two-way repeated-measures ANOVA (condition and distance factors). Gastrointestinal discomfort was analyzed qualitatively. Compared with placebo (pH 7.37 ± 0.02, [HCO3]: 27.5 ± 2.6 mmol·L), the NaHCO3 ingestion resulted in a preexercise blood alkalosis (pH +0.06 ± 0.04, [HCO3]: +4.4 ± 2.0 mmol·L, P < 0.05), whereas NH4Cl resulted in a blood acidosis (pH -0.05 ± 0.03, [HCO3]: -4.8 ± 2.1 mmol·L, P < 0.05). Anaerobic energy expenditure rate and PO were reduced throughout the trial in NH4Cl compared with placebo and NaHCO3, resulting in a lower total anaerobic work and impaired performance (P < 0.05). Plasma lactate, V˙CO2, and end-tidal CO2 partial pressure were lower and the V˙E/V˙CO2 higher throughout the trial in NH4Cl compared with placebo and NaHCO3 (P < 0.05). There was no difference between NaHCO3 and placebo for any of these variables (P > 0.05). Minimal gastrointestinal distress was noted in all conditions. Preexercise acidosis, but not alkalosis, affects anaerobic metabolism and PO during a 4-km cycling TT.

Intravenous hypertonic saline solution (7.5%) and oral electrolytes to treat of calves with noninfectious diarrhea and metabolic acidosis.

PubMed

Leal, M L R; Fialho, S S; Cyrillo, F C; Bertagnon, H G; Ortolani, E L; Benesi, F J

2012-01-01

The aim of this study was to compare the efficacy of treating osmotic diarrhea and dehydration in calves with hypertonic saline solution (HSS) IV, isotonic electrolyte solution (IES) PO, and a combination of these 2 solutions (HSS + IES). Eighteen male calves 8-30 days of age were used to evaluate the efficacy of 3 methods of fluid therapy after induction of osmotic diarrhea and dehydration. The diarrhea and dehydration were induced by administration of saccharose, spironolactone, and hydrochlorothiazide for 48 hours. The animals were randomly divided into 3 experimental groups: Group 1: 7.2% hypertonic saline solution-HSS (5 mL/kg IV); Group 2: oral isotonic electrolyte solution IES (60 mL/kg PO); or Group 3: HSS+IES. Clinical signs and laboratory finding observed 48 hours post-induction (Time 0) included diarrhea, dehydration, lethargy, and metabolic acidosis. Calves treated with HSS + IES experienced decreases in hematocrit, total protein concentration, albumin concentration, urea nitrogen concentration, and plasma volume as well as increases in blood pH, blood bicarbonate concentration, and central venous pressure between 1 and 3 hours post-treatment. These findings also were observed in animals treated with IES, however, at a slower rate than in the HSS + IES-treated animals. Animals treated with HSS continued to display signs of dehydration, lethargy, and metabolic acidosis 24 hours post-treatment. Treatment with a combination of HSS and IES produced rapid and sustainable correction of hypovolemia and metabolic acidosis in calves with noninfections diarrhea and dehydration. Copyright © 2012 by the American College of Veterinary Internal Medicine.

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

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

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.

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

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.

Pyruvate in reduced osmolarity oral rehydration salt corrected lactic acidosis in sever scald rats.

PubMed

Liu, Rui; Wang, Shu-Ming; Li, Zong-Yu; Yu, Wen; Zhang, Hui-Ping; Zhou, Fang-Qiang

2018-06-01

A novel pyruvate-based oral rehydration salt (Pyr-ORS) was demonstrated of superiority over bicarbonate- or citrate-based one to preserve organ function and correct lactic acidosis in rehydration of lethal shock in animals. This study further compared these effects between low-osmolar Pyr-ORS and equimolar citrate-based counterpart. Eighty rats, using a fatal burn shock model, were randomized into four groups (two subgroups per group: n = 10): the sham group (group SR), Pyr-ORS group (group PR), WHO-ORS III group (group CR), and no rehydration group. ORS was delivered by manual gavage during 24 h following burns. Oral administration consisted of half of counted volume in the initial 8 h plus the rest in the later 16 h. Systemic hemodynamics, visceral organ surface blood flow, organ function, and metabolic acidosis were determined at 8 h and 24 h after burn. Another set of rats with identical surgical procedures without tests was observed for survival. Survival was markedly improved in the groups PR and CR; the former showed a higher survival rate than the latter at 24 h (40% versus 20%, P < 0.05). Systemic hemodynamics, visceral blood flow, and function of heart, liver, and kidney were greatly restored in group PR, compared with group CR (all P < 0.05). Hypoxic lactic acidosis was efficiently reversed in group PR, instead of group CR, (pH 7.36 versus 7.11, base excess 2.1 versus -9.1 mmol/L, lactate 4.28 versus 8.18 mmol/L; all P < 0.05) at 24 h after injury. Pyruvate was advantageous over citrate in low-osmolar ORS for protection of organs and survival; pyruvate, but not citrate, in the ORS corrected hypoxic lactic acidosis in rats subjected to lethal burn shock in 24 h. Copyright © 2018 Elsevier Inc. All rights reserved.

Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect

PubMed Central

Celotto, A.C.; Ferreira, L.G.; Capellini, V.K.; Albuquerque, A.A.S.; Rodrigues, A.J.; Evora, P.R.B.

2015-01-01

Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control. PMID:26648089

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.

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

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.

Correction of metabolic acidosis in hemodialysis: consequences on serum leptin and mineral metabolism.

PubMed

Bales, Alessandra M; Moysés, Rosa M A; dos Reis, Luciene M; Graciolli, Fabiana G; Hung, James; Martins Castro, Manuel Carlos; Elias, Rosilene M

2015-01-01

Hyperleptinemia and metabolic acidosis (MA) are frequently observed in patients on hemodialysis (HD). While the role of leptin in patients on HD is not completely understood, HD only partially corrects MA. Both leptin and acidosis have effect on bone disease. The goal of the present study was to evaluate the effects of MA correction on chronic kidney disease-mineral and bone disorder laboratory parameters and leptin levels. Forty-eight patients on HD, aged 43±19 years, were prospectively studied. Individual adjustments in the bicarbonate dialysate concentration were made to maintain pre-dialysis concentration≥22 mEq/l. Blood gas analysis was done monthly for 4 months (M1-M4). From M0 to M4, serum albumin increased (from 3.5 ±0.3 to 4.0±0.3 g/l, p<0.0001) while β2 microglobulin decreased (from 27.6±8.3 to 25.8±6.8 µg/ml, p=0.025). Serum leptin decreased in all but three patients, as well as leptin/adiponectin ratio (p<0.0001). There was a decrease in ionized serum calcium (from 5.0±0.5 to 4.7±0.5 mg/dl, p =0.002) and an increase in parathyroid hormone (PTH) [from 191 (85, 459) to 446 pg/ml (212, 983), p<0.0001] and in serum phosphate (from 5.4±1.4 to 5.8±1.1 mg/dl, p=0.048). MA correction in HD patients can decrease leptin, an atherogenic marker. The impact of such treatment extends to uremic bone disease, as decrease in serum calcium and increase in PTH. However, this could be an undesirable effect because it may aggravate a secondary hyperparathyroidism. Whether the reduction in leptin levels has impact on outcomes in patients on hemodialysis deserves further investigation.

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.

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.

FHR patterns that become significant in connection with ST waveform changes and metabolic acidosis at birth.

PubMed

Rosén, Karl G; Norén, Håkan; Carlsson, Ann

2018-04-18

Recent developments have produced new CTG classification systems and the question is to what extent these may affect the model of FHR + ST interpretation? The two new systems (FIGO2015 and SSOG2017) classify FHR + ST events differently from the current CTG classification system used in the STAN interpretation algorithm (STAN2007). Identify the predominant FHR patterns in connection with ST events in cases of cord artery metabolic acidosis missed by the different CTG classification systems. Indicate to what extent STAN clinical guidelines could be modified enhancing the sensitivity. Provide a pathophysiological rationale. Forty-four cases with umbilical cord artery metabolic acidosis were retrieved from a European multicenter database. Significant FHR + ST events were evaluated post hoc in consensus by an expert panel. Eighteen cases were not identified as in need of intervention and regarded as negative in the sensitivity analysis. In 12 cases, ST changes occurred but the CTG was regarded as reassuring. Visual analysis of the FHR + ST tracings revealed specific FHR patterns: Conclusion: These findings indicate FHR + ST analysis may be undertaken regardless of CTG classification system provided there is a more physiologically oriented approach to FHR assessment in connection with an ST event.

Moderate and intense muscular exercises induce marked intramyocellular metabolic acidosis in sickle cell disease mice.

PubMed

Chatel, Benjamin; Messonnier, Laurent A; Hourdé, Christophe; Vilmen, Christophe; Bernard, Monique; Bendahan, David

2017-05-01

Sickle cell disease (SCD) is associated with an impaired oxygen delivery to skeletal muscle that could alter ATP production processes. The present study aimed to determine the effects of sickle hemoglobin (HbS) on muscle pH homeostasis in response to exercise in homozygous (HbSS, n = 9) and heterozygous (HbAS, n = 10) SCD (Townes) mice in comparison to control (HbAA, n = 10) littermates. Magnetic resonance spectroscopy of phosphorus 31 enabled to measure intramuscular pH and phosphocreatine (PCr) concentration during rest-stimulation-recovery protocols at two different intensities. Maximal activity of some enzymes involved in muscle energetics and content of proteins involved in pH regulation were also investigated. HbSS mice presented a more pronounced exercise-induced intramuscular acidosis, whatever the intensity of exercise. Moreover, the depletion of PCr was also exacerbated in HbSS mice in response to intense exercise as compared with both HbAA and HbAS mice ( P < 0.01). While no difference was observed concerning proteins involved in muscle pH regulation, the activity of enolase (a glycolytic enzyme) was higher in both HbSS and HbAS mice as compared with controls ( P < 0.05). Interestingly, HbAS mice presented also metabolic impairments as compared with their control counterparts. This study has identified for the first time an exacerbated exercise-induced intramuscular acidosis in SCD mice. NEW & NOTEWORTHY The main finding of the present study was that the exercise-induced intramuscular acidosis was systematically more pronounced in sickle cell disease (SCD) mice as compared with their control counterparts. This result is important since it has been demonstrated in vitro that acidosis can trigger hemoglobin polymerization. From that point of view, our results tend to support the idea that high-intensity exercise may increase the risk of hemoglobin polymerization in SCD. Copyright © 2017 the American Physiological Society.

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.

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.

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�

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.

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 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

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 ...

Nitazoxanide induces in vitro metabolic acidosis in Taenia crassiceps cysticerci.

PubMed

Isac, Eliana; de A Picanço, Guaraciara; da Costa, Tatiane L; de Lima, Nayana F; de S M M Alves, Daniella; Fraga, Carolina M; de S Lino Junior, Ruy; Vinaud, Marina C

2016-12-01

Nitazoxanide (NTZ) is a broad-spectrum anti-parasitic drug used against a wide variety of protozoans and helminthes. Albendazole, its active metabolite albendazole sulfoxide (ABZSO), is one of the drugs of choice to treat both intestinal and tissue helminth and protozoan infections. However little is known regarding their impact on the metabolism of parasites. The aim of this study was to compare the in vitro effect of NTZ and ABZSO in the glycolysis of Taenia crassiceps cysticerci. The cysticerci were treated with 1.2; 0.6; 0.3 or 0.15 μg/mL of NTZ or ABZSO. Chromatographic and spectrophotometric analyses were performed in the culture medium and in the cysticerci extract. Regarding the glucose concentrations was possible to observe two responses: impair of the uptake and gluconeogenesis. The pyruvate concentrations were increased in the ABZSO treated group. Lactate concentrations were increased in the culture medium of NTZ treated groups. Therefore it was possible to infer that the metabolic acidosis was greater in the group treated with NTZ than in the ABZSO treated group indicating that this is one of the modes of action used by this drug to induce the parasite death. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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.

[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.

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.

Effects of clinically relevant acute hypercapnic and metabolic acidosis on the cardiovascular system: an experimental porcine study

PubMed Central

2013-01-01

Introduction Hypercapnic acidosis (HCA) that accompanies lung-protective ventilation may be considered permissive (a tolerable side effect), or it may be therapeutic by itself. Cardiovascular effects may contribute to, or limit, the potential therapeutic impact of HCA; therefore, a complex physiological study was performed in healthy pigs to evaluate the systemic and organ-specific circulatory effects of HCA, and to compare them with those of metabolic (eucapnic) acidosis (MAC). Methods In anesthetized, mechanically ventilated and instrumented pigs, HCA was induced by increasing the inspired fraction of CO2 (n = 8) and MAC (n = 8) by the infusion of HCl, to reach an arterial plasma pH of 7.1. In the control group (n = 8), the normal plasma pH was maintained throughout the experiment. Hemodynamic parameters, including regional organ hemodynamics, blood gases, and electrocardiograms, were measured in vivo. Subsequently, isometric contractions and membrane potentials were recorded in vitro in the right ventricular trabeculae. Results HCA affected both the pulmonary (increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR)) and systemic (increase in mean arterial pressure (MAP), decrease in systemic vascular resistance (SVR)) circulations. Although the renal perfusion remained unaffected by any type of acidosis, HCA increased carotid, portal, and, hence, total liver blood flow. MAC influenced the pulmonary circulation only (increase in MPAP and PVR). Both MAC and HCA reduced the stroke volume, which was compensated for by an increase in heart rate to maintain (MAC), or even increase (HCA), the cardiac output. The right ventricular stroke work per minute was increased by both MAC and HCA; however, the left ventricular stroke work was increased by HCA only. In vitro, the trabeculae from the control pigs and pigs with acidosis showed similar contraction force and action-potential duration (APD). Perfusion with an acidic

Acidosis Promotes Bcl-2 Family-mediated Evasion of Apoptosis

PubMed Central

Ryder, Christopher; McColl, Karen; Zhong, Fei; Distelhorst, Clark W.

2012-01-01

Acidosis arises in solid and lymphoid malignancies secondary to altered nutrient supply and utilization. Tumor acidosis correlates with therapeutic resistance, although the mechanism behind this effect is not fully understood. Here we show that incubation of lymphoma cell lines in acidic conditions (pH 6.5) blocks apoptosis induced by multiple cytotoxic metabolic stresses, including deprivation of glucose or glutamine and treatment with dexamethasone. We sought to examine the role of the Bcl-2 family of apoptosis regulators in this process. Interestingly, we found that acidic culture causes elevation of both Bcl-2 and Bcl-xL, while also attenuating glutamine starvation-induced elevation of p53-up-regulated modulator of apoptosis (PUMA) and Bim. We confirmed with knockdown studies that these shifts direct survival decisions during starvation and acidosis. Importantly, the promotion of a high anti- to pro-apoptotic Bcl-2 family member ratio by acidosis renders cells exquisitely sensitive to the Bcl-2/Bcl-xL antagonist ABT-737, suggesting that acidosis causes Bcl-2 family dependence. This dependence appears to be mediated, in part, by the acid-sensing G protein-coupled receptor, GPR65, via a MEK/ERK pathway. PMID:22685289

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.

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

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

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

Respiratory acidosis

MedlinePlus

Ventilatory failure; Respiratory failure; Acidosis - respiratory ... Causes of respiratory acidosis include: Diseases of the airways (such as asthma and COPD ) Diseases of the lung tissue (such as ...

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.

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

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

Effects of sodium hydroxide treatment of dried distillers' grains on digestibility, ruminal metabolism, and metabolic acidosis of feedlot steers.

PubMed

Freitas, T B; Relling, A E; Pedreira, M S; Santana Junior, H A; Felix, T L

2016-02-01

The objectives were to determine the optimum inclusion of NaOH necessary to buffer the acidity of dried distillers' grains with solubles (DDGS) and its effects on digestibility, ruminal metabolism, and metabolic acidosis in feedlot steers. Rumen cannulated Angus-crossed steers were blocked by BW (small: 555 ± 42 kg initial BW, = 4; large: 703 ± 85 kg initial BW, = 4) over four 21-d periods in a replicated 4 × 4 Latin square design. Steers were assigned to 1 of 4 dietary treatments: 1) 50% untreated DDGS, 2) 50% DDGS treated with 0.5% (DM basis) sodium hydroxide (NaOH), 3) 50% DDGS treated with 1.0% (DM basis) NaOH, and 4) 50% DDGS treated with 1.5% (DM basis) NaOH. The remainder of the diets, on a DM basis, was composed of 20% corn silage, 20% dry-rolled corn, and 10% supplement. Ruminal pH was not affected by treatments ( = 0.56) or by a treatment × time interaction ( = 0.15). In situ NDF and ruminal DM disappearance did not differ ( ≥ 0.49 and ≥ 0.47, respectively) among treatments. Similar to in situ results, apparent total tract DM and NDF digestibility were not affected ( ≥ 0.33 and ≥ 0.21, respectively) by increasing NaOH inclusion in the diets. Urinary pH increased (linear, < 0.01) with increasing NaOH concentration in the diet. Blood pH was not affected ( ≥ 0.20), and blood total CO and partial pressure of CO were similar ( ≥ 0.56 and ≥ 0.17, respectively) as NaOH increased in the diet. Increasing NaOH in the diet did not affect ( ≥ 0.21) ruminal concentrations of total VFA. There were no linear ( = 0.20) or quadratic ( = 0.20) effects of treatment on ruminal acetate concentrations, nor was there a treatment × time interaction ( = 0.22) for acetate. Furthermore, there were no effects ( ≥ 0.90) of NaOH inclusion on ruminal propionate concentration. However, there was a quadratic response ( = 0.01) of ruminal butyrate concentrations as NaOH inclusion increased in the diet; ruminal butyrate concentrations were greatest with the 0.5 and 1

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.

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

Life-threatening hypokalemia following rapid correction of respiratory acidosis.

PubMed

Hammond, Kendra; You, David; Collins, Eileen G; Leehey, David J; Laghi, Franco

2013-01-01

A 56-year-old woman with a history of paraplegia and chronic pain due to neuromyelitis optica (Devic's syndrome) was admitted to a spinal cord injury unit for management of a sacral decubitus ulcer. During the hospitalization, she required emergency transfer to the intensive care unit (ICU) because of progressive deterioration of respiratory muscle function, severe respiratory acidosis, obtundation and hypotension. Upon transfer to the ICU, arterial blood gas revealed severe acute-on-chronic respiratory acidosis (pH 7.00, PCO2 120 mm Hg, PO2 211 mm Hg). The patient was immediately intubated and mechanically ventilated. Intravenous fluid boluses of normal saline (10.5 L in about 24 h) and vasopressors were started with rapid correction of hypotension. In addition, she was given hydrocortisone. Within 40 min of initiation of mechanical ventilation, there was improvement in acute respiratory acidosis. Sixteen hours later, however, the patient developed life-threatening hypokalemia (K(+) of 2.1 mEq/L) and hypomagnesemia (Mg of 1.4 mg/dL). Despite aggressive potassium supplementation, hypokalemia continued to worsen over the next several hours (K(+) of 1.7 mEq/L). Urine studies revealed renal potassium wasting. We reason that the recalcitrant life-threatening hypokalemia was caused by several mechanisms including total body potassium depletion (chronic respiratory acidosis), a shift of potassium from the extracellular to intracellular space (rapid correction of respiratory acidosis with mechanical ventilation), increased sodium delivery to the distal nephron (normal saline resuscitation), hyperaldosteronism (secondary to hypotension plus administration of hydrocortisone) and hypomagnesemia. We conclude that rapid correction of respiratory acidosis, especially in the setting of hypotension, can lead to life-threatening hypokalemia. Serum potassium levels must be monitored closely in these patients, as failure to do so can lead to potentially lethal consequences

Severe metabolic alkalosis and recurrent acute on chronic kidney injury in a patient with Crohn's disease

PubMed Central

2010-01-01

Background Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate. Case Presentation Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn. The patient had undergone multiple resections of the intestine and suffered from chronic kidney disease. He was now referred to our clinic for recurrent acute kidney injury, the nature of which was pre-renal due to profound volume depletion. Renal failure was associated with marked hypochloremic metabolic alkalosis which only responded to high volume repletion and high dose blockade of gastric hypersecretion. Intestinal failure with stomal fluid losses of up to 5.7 litres per day required port implantation to commence parenteral nutrition. Fluid and electrolyte replacement rapidly improved renal function and acid base homeostasis. Conclusions This case highlights the important role of gastrointestinal function to maintain acid base status in patients with Crohn's disease. PMID:20398419

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.

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.

Acute starvation ketoacidosis in pregnancy with severe hypertriglyceridemia: A case report.

PubMed

Hui, Li; Shuying, Li

2018-05-01

Pregnant women are more prone to ketosis due to the relative insulin resistance, accelerated lipolysis and increased free fatty acids. We report a pregnant woman with hyperlipidemia, who experienced severe metabolic acidosis after a short period of starvation. Based on her clinical symptoms, exclusion diagnosis and therapeutic diagnosis, her condition was diagnosed as starvation ketoacidosis. An emergency caesarean section under general anesthesia was implemented 2 hours after her admission. The metabolic acidosis was treated with fluid resuscitation using compound sodium lactate, bicarbonate, and 5% dextrose together with insulin 6U. Both mother and baby were discharged clinically well. Starvation ketoacidosis may happen in special patient who was in pregnancy and with severe hypertriglyceridemia, after just one day fasting and vomiting.

L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome

PubMed Central

Rodan, Lance H.; Wells, Greg D.; Banks, Laura; Thompson, Sara; Schneiderman, Jane E.; Tein, Ingrid

2015-01-01

Objective To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. Methods We performed a case control study in 3 MELAS siblings (m.3243A>G tRNAleu(UUR) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO2peak) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. Results At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 31P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg2+ (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO2peak. On 31P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. Significance These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Classification of Evidence Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. Trial Registration ClinicalTrials.gov NCT01603446. PMID:25993630

L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome.

PubMed

Rodan, Lance H; Wells, Greg D; Banks, Laura; Thompson, Sara; Schneiderman, Jane E; Tein, Ingrid

2015-01-01

To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by (31)Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. We performed a case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR)) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO(2peak)) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 3(1)P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg(2+) (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO(2peak). On (31)P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. ClinicalTrials.gov NCT01603446.

Veno-venous extracorporeal CO2 removal for the treatment of severe respiratory acidosis: pathophysiological and technical considerations.

PubMed

Karagiannidis, Christian; Kampe, Kristin Aufm; Sipmann, Fernando Suarez; Larsson, Anders; Hedenstierna, Goran; Windisch, Wolfram; Mueller, Thomas

2014-06-17

While non-invasive ventilation aimed at avoiding intubation has become the modality of choice to treat mild to moderate acute respiratory acidosis, many severely acidotic patients (pH <7.20) still need intubation. Extracorporeal veno-venous CO2 removal (ECCO2R) could prove to be an alternative. The present animal study tested in a systematic fashion technical requirements for successful ECCO2R in terms of cannula size, blood and sweep gas flow. ECCO2R with a 0.98 m(2) surface oxygenator was performed in six acidotic (pH <7.20) pigs using either a 14.5 French (Fr) or a 19Fr catheter, with sweep gas flow rates of 8 and 16 L/minute, respectively. During each experiment the blood flow was incrementally increased to a maximum of 400 mL/minute (14.5Fr catheter) and 1000 mL/minute (19Fr catheter). Amelioration of severe respiratory acidosis was only feasible when blood flow rates of 750 to 1000 mL/minute (19Fr catheter) were used. Maximal CO2-elimination was 146.1 ± 22.6 mL/minute, while pH increased from 7.13 ± 0.08 to 7.41 ± 0.07 (blood flow of 1000 mL/minute; sweep gas flow 16 L/minute). Accordingly, a sweep gas flow of 8 L/minute resulted in a maximal CO2-elimination rate of 138.0 ± 16.9 mL/minute. The 14.5Fr catheter allowed a maximum CO2 elimination rate of 77.9 mL/minute, which did not result in the normalization of pH. Veno-venous ECCO2R may serve as a treatment option for severe respiratory acidosis. In this porcine model, ECCO2R was most effective when using blood flow rates ranging between 750 and 1000 mL/minute, while an increase in sweep gas flow from 8 to 16 L/minute had less impact on ECCO2R in this setting.

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

[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.

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.

Consideration of alternative causes of lactic acidosis: Thiamine deficiency in malignancy.

PubMed

Dean, Ryan K; Subedi, Rogin; Gill, Dalvir; Nat, Amitpal

2017-08-01

Lactic acidosis is a common metabolic acidosis characterized by increased serum lactate and is usually associated with a decreased blood pH. Lactic acidosis has many different causes but has been differentiated into type A, hypoxic causes, and type B, non-hypoxic causes. Tissue hypoxia, type A, is the most common cause, usually secondary to processes such as sepsis and multi-organ failure. Type A must be differentiated from type B in the correct clinical setting as treatments are vastly different. Type B causes may include drug side-effects, toxins, enzymatic defects, inherited or acquired, any of which may lead to overproduction or underutilization of lactate. However, as most clinicians are more familiar, and likely more initially concerned with hypoxic etiologies, evaluation is directed toward finding the source of hypoperfusion or hypoxia, and thus generally leading to a delay in discovering a type B cause (or mixed type A and type B). Here we describe a case of lactic acidosis in the setting of thiamine deficiency thought to be secondary to advanced lung cancer. The purpose of this paper is to bring awareness to the clinician to consider other causes of lactic acidosis when evaluating a patient. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

[Metformin-associated lactic acidosis in a patient with pre-existing risk factors].

PubMed

Becker, C; Luginbühl, A; Pittl, U; Schlienger, R

2005-09-07

Lactic acidosis is a serious clinical situation associated with a high case fatality rate. Lactic acidosis is particularly found in conditions with an insufficient supply of oxigen in the tissue. Other causes for lactic acidosis can be hepatic or renal insufficiency. For the therapy of overweight patients with type 2 diabetes metformin is the first choice if diet and physical training have been ineffective. Metformin, however, has the potential to increase serumlactate. Therefore its ability to cause lactic acidosis is controversely discussed. We present a 64-year-old female patient with metformin-associated lactic acidosis. She had several pre-existing risk factors to develop a lactic acidosis. On her referral to the hospital she suffered from acute renal failure which is considered to be a contraindication for the use of metformin.

Diet-induced acidosis and alkali supplementation.

PubMed

Della Guardia, Lucio; Roggi, Carla; Cena, Hellas

2016-11-01

Western diet, high in protein-rich foods and poor in vegetables, is likely to be responsible for the development of a moderate acid excess leading to metabolism deregulation and the onset or worsening of chronic disturbances. Available findings seem to suggest that diets with high protein/vegetables ratio are likely to induce the development of calcium lithiasis, especially in predisposed subjects. Moreover, some evidence supports the hypothesis of bone metabolism worsening and enhanced bone loss following acid-genic diet consumption although available literature seems to lack direct and conclusive evidence demonstrating pathological bone loss. According to other evidences, diet-induced acidosis is likely to induce or accelerate muscle wasting or sarcopenia, especially among elderlies. Furthermore, recent epidemiological findings highlight a specific role of dietary acid load in glucose metabolism deregulation and insulin resistance. The aim of this review is to investigate the role of acid-genic diets in the development of the mentioned metabolic disorders focusing on the possible clinical improvements exerted by alkali supplementation.

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.

Impact of membrane lung surface area and blood flow on extracorporeal CO2 removal during severe respiratory acidosis.

PubMed

Karagiannidis, Christian; Strassmann, Stephan; Brodie, Daniel; Ritter, Philine; Larsson, Anders; Borchardt, Ralf; Windisch, Wolfram

2017-12-01

Veno-venous extracorporeal CO 2 removal (vv-ECCO 2 R) is increasingly being used in the setting of acute respiratory failure. Blood flow rates through the device range from 200 ml/min to more than 1500 ml/min, and the membrane surface areas range from 0.35 to 1.3 m 2 . The present study in an animal model with similar CO 2 production as an adult patient was aimed at determining the optimal membrane lung surface area and technical requirements for successful vv-ECCO 2 R. Four different membrane lungs, with varying lung surface areas of 0.4, 0.8, 1.0, and 1.3m 2 were used to perform vv-ECCO 2 R in seven anesthetized, mechanically ventilated, pigs with experimentally induced severe respiratory acidosis (pH 7.0-7.1) using a 20Fr double-lumen catheter with a sweep gas flow rate of 8 L/min. During each experiment, the blood flow was increased stepwise from 250 to 1000 ml/min. Amelioration of severe respiratory acidosis was only feasible when blood flow rates from 750 to 1000 ml/min were used with a membrane lung surface area of at least 0.8 m 2 . Maximal CO 2 elimination was 150.8 ml/min, with pH increasing from 7.01 to 7.30 (blood flow 1000 ml/min; membrane lung 1.3 m 2 ). The membrane lung with a surface of 0.4 m 2 allowed a maximum CO 2 elimination rate of 71.7 mL/min, which did not result in the normalization of pH, even with a blood flow rate of 1000 ml/min. Also of note, an increase of the surface area above 1.0 m 2 did not result in substantially higher CO 2 elimination rates. The pressure drop across the oxygenator was considerably lower (<10 mmHg) in the largest membrane lung, whereas the smallest revealed a pressure drop of more than 50 mmHg with 1000 ml blood flow/min. In this porcine model, vv-ECCO 2 R was most effective when using blood flow rates ranging between 750 and 1000 ml/min, with a membrane lung surface of at least 0.8 m 2 . In contrast, low blood flow rates (250-500 ml/min) were not sufficient to completely correct severe

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.

Protective Role of Acidic pH-Activated Chloride Channel in Severe Acidosis-Induced Contraction from the Aorta of Spontaneously Hypertensive Rats

PubMed Central

Ma, Zhiyong; Qi, Jia; Fu, Zhijie; Ling, Mingying; Li, Li; Zhang, Yun

2013-01-01

Severe acidic pH-activated chloride channel (ICl,acid) has been found in various mammalian cells. In the present study, we investigate whether this channel participates in reactions of the thoracic aorta to severe acidosis and whether it plays a role in hypertension. We measured isometric contraction in thoracic aorta rings from spontaneously hypertensive rats (SHRs) and normotensive Wistar rats. Severe acidosis induced contractions of both endothelium-intact and -denuded thoracic aorta rings. In Wistar rats, contractions did not differ at pH 6.4, 5.4 and 4.4. However, in SHRs, contractions were higher at pH 5.4 or 4.4 than pH 6.4, with no difference between contractions at pH 5.4 and 4.4. Nifedipine, ICl,acid blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and 4,4′-diisothiocyanatostilbene-2, 2′-disulfonic acid (DIDS) inhibited severe acidosis-induced contraction of aortas at different pH levels. When blocking ICl,acid, the remnant contraction was greater at pH 4.4 than pH 5.4 and 6.4 for both SHRs and Wistar rats. With nifedipine, the remnant contraction was greatly reduced at pH 4.4 as compared with at pH 6.4 and 5.4. With NPPB or DIDS, the ratio of remnant contractions at pH 4.4 and 5.4 (R4.4/5.4) was lower for SHRs than Wistar rats (all <1). However, with nifedipine, the R4.4/5.4 was higher for SHRs than Wistar rats (both >1). Furthermore, patch clamp recordings of ICl,acid and intracellular Ca2+ measurements in smooth muscle cells confirmed these findings. ICl,acid may protect arteries against excess vasoconstriction under extremely acidic extracellular conditions. This protective effect may be decreased in hypertension. PMID:23580361

Effects of seasonal vitamin D deficiency and respiratory acidosis on bone metabolism markers in submarine crewmembers during prolonged patrols.

PubMed

Holy, Xavier; Collombet, Jean-Marc; Labarthe, Frédéric; Granger-Veyron, Nicolas; Bégot, Laurent

2012-02-01

The aim of the study was to determine the seasonal influence of vitamin D status on bone metabolism in French submariners over a 2-mo patrol. Blood samples were collected as follows: prepatrol and patrol days 20, 41, and 58 on crewmembers from both a winter (WP; n = 20) and a summer patrol (SP; n = 20), respectively. Vitamin D status was evaluated for WP and SP. Moreover, extended parameters for acid-base balance (Pco(2), pH, and bicarbonate), bone metabolism (bone alkaline phosphatase and COOH-terminal telopeptide of type I collagen), and mineral homeostasis (parathyroid hormone, ionized calcium and phosphorus) were scrutinized. As expected, SP vitamin D status was higher than WP vitamin D status, regardless of the considered experimental time. A mild chronic respiratory acidosis (CRA) was identified in both SP and WP submariners, up to patrol day 41. Such an occurrence paired up with an altered bone remodeling coupling (decreased bone alkaline phosphatase-to-COOH-terminal telopeptide of type I collagen ratio). At the end of the patrol (day 58), a partial compensation of CRA episode, combined with a recovered normal bone remodeling coupling, was observed in SP, not, however, in WP submariners. The mild CRA episode displayed over the initial 41-day submersion period was mainly induced by a hypercapnia resulting from the submarine-enriched CO(2) level. The correlated impaired bone remodeling may imply a physiological attempt to compensate this acidosis via bone buffering. On patrol day 58, the discrepancy observed in terms of CRA compensation between SP and WP may result from the seasonal influence on vitamin D status.

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.

Severe Respiratory Acidosis in Status Epilepticus as a Possible Etiology of Sudden Death in Lesch-Nyhan Disease: A Case Report and Review of the Literature.

PubMed

Christy, Alison; Nyhan, William; Wilson, Jenny

2017-01-01

Lesch-Nyhan disease (LND) is an X-linked disorder of purine metabolism, associated with self-mutilation, dystonia, and chorea. Seizures are uncommon in LND. Patients with LND are at risk for sudden and unexpected death. The etiology of this is unknown, but appears to occur from a respiratory process. We propose that respiratory failure secondary to subclinical seizure may lead to sudden death in these patients. We report a case of an 11-year-old boy with LND who had two episodes of nocturnal gasping. The second event was immediately followed by a 10 min generalized seizure. Upon arrival at the hospital, an arterial blood gas test revealed a severe respiratory acidosis. Following aggressive treatment of his seizures, this patient did well, and was discharged home on oxcarbazepine with rectal diazepam. No further seizures have been noted in 1 year of follow-up. In this case report and review, we hypothesize that sudden death from respiratory failure in Lesch-Nyhan disease may in some cases be due to seizure-induced respiratory failure, akin to sudden unexpected death in epilepsy (SUDEP). We suggest screening for paroxysmal respiratory events; consideration of electroencephalography for patients with LND presenting in respiratory distress or failure; and consideration of more aggressive treatment of seizures in these patients. Brief Summary:We present an 11-year-old boy with Lesch-Nyhan disease (LND) who developed respiratory failure and severe respiratory acidosis from his first known seizure, which evolved to subclinical status epilepticus. We propose that patients with LND have a predisposition to respiratory failure and sudden death, which in some cases may be provoked by seizure (sudden unexpected death in epilepsy, or SUDEP).

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

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

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.

Acute pancreatitis and severe hypertriglyceridaemia masking unsuspected underlying diabetic ketoacidosis.

PubMed

Aboulhosn, Kewan; Arnason, Terra

2013-09-04

A healthy 18-year-old girl presented to a local emergency room with 48 h of abdominal pain and vomiting. A radiological and biochemical diagnosis of moderate acute pancreatitis was made. Bloodwork demonstrated prominent hypertriglyceridaemia (HTG) of 19.5 mmol/L (severe HTG: 11.2-22.4), detectable urine ketones and a random blood glucose of 13 mmol/L dropping to 10.5 mmol/L on repeat (normal random <11). Ketone levels were deemed consistent with fasting ketosis after 48 h of vomiting. There was no known history of diabetes in the patient. Management included aggressive rehydration and pain control, yet the patient rapidly decompensated into shock requiring intensive care unit support. Blood gases revealed severe metabolic acidosis (pH 6.99) and unsuspected underlying diabetic ketoacidosis was diagnosed. The HTG gradually resolved following intravenous fluids and insulin infusion with slower correction of the metabolic acidosis. Importantly, her glycated haemoglobin was 12%, indicating the silent presence of chronic glucose elevations.

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.

Tonometry revisited: perfusion-related, metabolic, and respiratory components of gastric mucosal acidosis in acute cardiorespiratory failure.

PubMed

Jakob, Stephan M; Parviainen, Ilkka; Ruokonen, Esko; Kogan, Alexander; Takala, Jukka

2008-05-01

Mucosal pH (pHi) is influenced by local perfusion and metabolism (mucosal-arterial pCO2 gradient, DeltapCO2), systemic metabolic acidosis (arterial bicarbonate), and respiration (arterial pCO2). We determined these components of pHi and their relation to outcome during the first 24 h of intensive care. We studied 103 patients with acute respiratory or circulatory failure (age, 63+/-2 [mean+/-SEM]; Acute Physiology and Chronic Health Evaluation II score, 20+/-1; Sequential Organ Failure Assessment score, 8+/-0). pHi, and the effects of bicarbonate and arterial and mucosal pCO2 on pHi, were assessed at admission, 6, and 24 h. pHi was reduced (at admission, 7.27+/-0.01) due to low arterial bicarbonate and increased DeltapCO2. Low pHi (<7.32) at admission (n=58; mortality, 29% vs. 13% in those with pHi>or=7.32 at admission; P=0.061) was associated with an increased DeltapCO2 in 59% of patients (mortality, 47% vs. 4% for patients with low pHi and normal DeltapCO2; P=0.0003). An increased versus normal DeltapCO2, regardless of pHi, was associated with increased mortality at admission (51% vs. 5%; P<0.0001; n=39) and at 6 h (34% vs. 13%; P=0.016; n=45). A delayed normalization or persistently low pHi (n=47) or high DeltapCO2 (n=25) was associated with high mortality (low pHi [34%] vs. high DeltapCO2 [60%]; P=0.046). In nonsurvivors, hypocapnia increased pHi at baseline, 6, and 24 h (all Pacidosis. Inadequate tissue perfusion may persist despite stable hemodynamics and contributes to poor outcome.

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

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.

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.

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.

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.

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

Relationship of severity of subacute ruminal acidosis to rumen fermentation, chewing activities, sorting behavior, and milk production in lactating dairy cows fed a high-grain diet.

PubMed

Gao, X; Oba, M

2014-05-01

The objectives of the current study were to evaluate the variation in severity of subacute ruminal acidosis (SARA) among lactating dairy cows fed a high-grain diet and to determine factors characterizing animals that are tolerant to high-grain diets. Sixteen ruminally cannulated late-lactating dairy cows (days in milk=282 ± 33.8; body weight=601 ± 75.9 kg) were fed a high-grain diet consisting of 35% forage and 65% concentrate mix. After 17 d of diet adaptation, chewing activities were monitored for a 24-h period and ruminal pH was measured every 30s for 72 h. Acidosis index, defined as the severity of SARA (area of pH <5.8) divided by dry matter intake (DMI), was determined for individual animals to assess the severity of SARA normalized for a feed intake level. Although all cows were fed the same diet, minimum pH values ranged from 5.16 to 6.04, and the acidosis index ranged from 0.0 to 10.9 pH · min/kg of DMI. Six cows with the lowest acidosis index (0.04 ± 0.61 pH · min/kg) and 4 with the highest acidosis index (7.67 ± 0.75 pH · min/kg) were classified as animals that were tolerant and susceptible to the high-grain diet, respectively. Total volatile fatty acid concentration and volatile fatty acid profile were not different between the groups. Susceptible animals sorted against long particles, whereas tolerant animals did not (sorting index=87.6 vs. 97.9, respectively). However, the tolerant cows had shorter total chewing time (35.8 vs. 45.1 min/kg of DMI). In addition, although DMI, milk yield, and milk component yields did not differ between the groups, milk urea nitrogen concentration was higher for tolerant cows compared with susceptible cows (12.8 vs. 8.6 mg/dL), which is possibly attributed to less organic matter fermentation in the rumen of tolerant cows. These results suggest that a substantial variation exists in the severity of SARA among lactating dairy cows fed the same high-grain diet, and that cows tolerant to the high-grain diet might be

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.

[Serum creatine kinase activity in dogs and cats with metabolic diseases].

PubMed

Neumann, S

2005-09-01

Elevated Creatine kinase-activitiy (CK) indicates disturbances of the muscle cell integrity. In addition to primary muscle disease, like trauma, inflammation or dystrophy, diseases of other organs can lead to secondary muscle involvement, which will be indicated by increased serum activities of the CK. The mechanisms of muscle cell disturbance are still unknown. An elevated protein catabolism in the muscle cell is suspected. In the present study we investigated, if dogs and cats with metabolic diseases have increased CK-activity in the serum. From 34 dogs and cats in a group with different metabolic diseases without metabolic acidosis 19% of the dogs and 50% of the cats had increased CK-activity in the serum. From 33 dogs and cats with different metabolic diseases connected with metabolic acidosis 86% of the dogs and 95% of the cats had simultaneously increased CK-activity in the serum. In comparison to healthy dogs and cats animals with metabolic diseases have significant and in cases of metabolic di-seases with metabolic acidosis cats have high significant elevation (dogs significant) of CK-activity in the serum. There was no significant correlation between the groups of patients. In conclusion we think that our results show that metabolic diseases often induce secondary myopathy, measured by CK-activity in the serum, but metabolic acidosis has no direct influence on elevated CK activity in dogs and cats.

Acute pancreatitis and severe hypertriglyceridaemia masking unsuspected underlying diabetic ketoacidosis

PubMed Central

Aboulhosn, Kewan; Arnason, Terra

2013-01-01

A healthy 18-year-old girl presented to a local emergency room with 48 h of abdominal pain and vomiting. A radiological and biochemical diagnosis of moderate acute pancreatitis was made. Bloodwork demonstrated prominent hypertriglyceridaemia (HTG) of 19.5 mmol/L (severe HTG: 11.2–22.4), detectable urine ketones and a random blood glucose of 13 mmol/L dropping to 10.5 mmol/L on repeat (normal random <11). Ketone levels were deemed consistent with fasting ketosis after 48 h of vomiting. There was no known history of diabetes in the patient. Management included aggressive rehydration and pain control, yet the patient rapidly decompensated into shock requiring intensive care unit support. Blood gases revealed severe metabolic acidosis (pH 6.99) and unsuspected underlying diabetic ketoacidosis was diagnosed. The HTG gradually resolved following intravenous fluids and insulin infusion with slower correction of the metabolic acidosis. Importantly, her glycated haemoglobin was 12%, indicating the silent presence of chronic glucose elevations. PMID:24005972

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

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.

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

The mitochondrial myopathy encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome: a review of treatment options.

PubMed

Scaglia, Fernando; Northrop, Jennifer L

2006-01-01

Mitochondrial encephalomyopathies are a multisystemic group of disorders that are characterised by a wide range of biochemical and genetic mitochondrial defects and variable modes of inheritance. Among this group of disorders, the mitochondrial myopathy, encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome is one of the most frequently occurring, maternally inherited mitochondrial disorders. As the name implies, stroke-like episodes are the defining feature of the MELAS syndrome, often occurring before the age of 15 years. The clinical course of this disorder is highly variable, ranging from asymptomatic, with normal early development, to progressive muscle weakness, lactic acidosis, cognitive dysfunction, seizures, stroke-like episodes, encephalopathy and premature death. This syndrome is associated with a number of point mutations in the mitochondrial DNA, with over 80% of the mutations occurring in the dihydrouridine loop of the mitochondrial transfer RNA(Leu(UUR)) [tRNA(Leu)((UUR))] gene. The pathophysiology of the disease is not completely understood; however, several different mechanisms are proposed to contribute to this disease. These include decreased aminoacylation of mitochondrial tRNA, resulting in decreased mitochondrial protein synthesis; changes in calcium homeostasis; and alterations in nitric oxide metabolism. Currently, no consensus criteria exist for treating the MELAS syndrome or mitochondrial dysfunction in other diseases. Many of the therapeutic strategies used have been adopted as the result of isolated case reports or limited clinical studies that have included a heterogeneous population of patients with the MELAS syndrome, other defects in oxidative phosphorylation or lactic acidosis due to disorders of pyruvate metabolism. Current approaches to the treatment of the MELAS syndrome are based on the use of antioxidants, respiratory chain substrates and cofactors in the form of vitamins; however, no consistent benefits

Severe metabolic alkalosis in pregnancy

PubMed Central

Frise, Charlotte; Noori, Muna

2013-01-01

Summary Metabolic alkalosis is uncommon in pregnancy and is most often the result of severe vomiting. If this is present at the time of delivery, transient metabolic derangement in the fetus can occur, potentially requiring additional organ support. A 22-year-old woman is described, who presented at 37 weeks gestation with a severe metabolic alkalosis, vomiting and acute renal and hepatic impairment. The investigations, management options and maternal and fetal outcome are described. PMID:27708709

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

Correction of metabolic acidosis improves insulin resistance in chronic kidney disease.

PubMed

Bellasi, Antonio; Di Micco, Lucia; Santoro, Domenico; Marzocco, Stefania; De Simone, Emanuele; Cozzolino, Mario; Di Lullo, Luca; Guastaferro, Pasquale; Di Iorio, Biagio

2016-10-22

Correction of metabolic acidosis (MA) with nutritional therapy or bicarbonate administration is widely used in chronic kidney disease (CKD) patients. However, it is unknown whether these interventions reduce insulin resistance (IR) in diabetic patients with CKD. We sought to evaluate the effect of MA correction on endogenous insulin action in diabetic type 2 (DM2) CKD patients. A total of 145 CKD subjects (83 men e 62 women) with DM2 treated with oral antidiabetic drugs were included in the study and followed up to 1 year. All patients were randomly assigned 1:1 to either open-label (A) oral bicarbonate to achieve serum bicarbonate levels of 24-28 mmol/L (treatment group) or (B) no treatment (control group). The Homeostatic model assessment (HOMA) index was used to evaluate IR at study inception and conclusion. Parametric and non-parametric tests as well as linear regression were used. At baseline no differences in demographic and clinical characteristics between the two groups was observed. Average dose of bicarbonate in the treatment group was 0.7 ± 0.2 mmol/kg. Treated patients showed a better metabolic control as confirmed by lower insulin levels (13.4 ± 5.2 vs 19.9 ± 6.3; for treated and control subjects respectively; p < 0.001), Homa-IR (5.9[5.0-7.0] vs 6.3[5.3-8.2]; p = 0.01) and need for oral antidiabetic drugs. The serum bicarbonate and HOMA-IR relationship was non-linear and the largest HOMA-IR reduction was noted for serum bicarbonate levels between 24 and 28 mmol/l. Adjustment for confounders, suggests that serum bicarbonate rather than treatment drives the effect on HOMA-IR. Serum bicarbonate is related to IR and the largest HOMA-IR reduction is noted for serum bicarbonate between 24 and 28 mmol/l. Treatment with bicarbonate influences IR. However, changes in serum bicarbonate explains the effect of treatment on HOMA index. Future efforts are required to validate these results in diabetic and non-diabetic CKD patients. The

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

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.

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.

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.

Genotype-Phenotype Analysis in Pediatric Patients with Distal Renal Tubular Acidosis.

PubMed

Park, Eujin; Cho, Myung Hyun; Hyun, Hye Sun; Shin, Jae Il; Lee, Joo Hoon; Park, Young Seo; Choi, Hyun Jin; Kang, Hee Gyung; Cheong, Hae Il

2018-01-01

Primary distal renal tubular acidosis (dRTA) in children is a rare genetic disorder, and three causative mutated genes have been identified: SLC4A1, ATP6V1B1, and ATP6V0A4. We analyzed the prevalence and phenotypic differences of genetic mutations in children with dRTA. A total of 17 children with dRTA were enrolled in the study. All patients underwent genetic testing for all three candidate genes. Pathogenic mutations, including six novel mutations, were detected in 15 (88.2%) patients: dominant SLC4A1 mutations in ten (58.8%) patients, recessive ATP6V0A4 mutations in three (17.6%) patients, and recessive ATP6V1B1 mutations in two (11.8%) patients. Compared to other patients, patients with SLC4A1 mutations showed an older age of onset (3.7 ± 2.6 years) and less severe metabolic acidosis at initial presentation. All patients developed nephrocalcinosis, and sensorineural hearing loss was observed in two patients with ATP6V1B1 mutations. Three (17.6%) patients had decreased renal function (chronic kidney disease stage 2), and five (29.4%) patients had persistent growth retardation at the last follow-up. Long-term prognosis showed no genotype-phenotype correlation. SLC4A1 is the most common defective gene in Korean children with dRTA. Patients with SLC4A1 mutations show later onset and milder disease severity. Long-term follow-up of hearing ability, renal function, and growth is necessary for patients with dRTA. © 2018 The Author(s). Published by S. Karger AG, Basel.

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.

Metabolic studies of transient tyrosinemia in premature infants

NASA Technical Reports Server (NTRS)

Fernbach, S. A.; Summons, R. E.; Pereira, W. E.; Duffield, A. M.

1975-01-01

The recently developed technique of gas chromatography-mass spectrometry supported by computer has considerably improved the analysis of physiologic fluids. This study attempted to demonstrate the value of this system in the investigation of metabolite patterns in urine in two metabolic problems of prematurity, transient tyrosinemia and late metabolic acidosis. Serial 24-hr urine specimens were analyzed in 9 infants. Transient tyrosinemia, characterized by 5- 10-fold increases over basal excretion of tyrosine, p-hydroxyphenyllactate, and p-hydroxyphenylpyruvate in urine, was noted in five of the infants. Late metabolic acidosis was seen in four infants, but bore no relation to transient tyrosinemia.

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.

[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.

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.

Age specific fast breathing in under-five diarrheal children in an urban hospital: Acidosis or pneumonia?

PubMed

Nuzhat, Sharika; Ahmed, Tahmeed; Kawser, Chowdhury Ali; Khan, Azharul Islam; Islam, S M Rafiqul; Shahrin, Lubaba; Shahunja, K M; Shahid, Abu S M S B; Al Imran, Abdullah; Chisti, Mohammod Jobayer

2017-01-01

Children with diarrhea often present with fast breathing due to metabolic acidosis from dehydration. On the other hand, age specific fast breathing is the cornerstone for the diagnosis of pneumonia following classification of pneumonia recommended by the World Health Organization (WHO). Correction of metabolic acidosis by rehydrating the diarrheal children requires time, which delays early initiation of appropriate antimicrobials for pneumonia and thereby increases the risk of deaths. We need to further investigate the simple clinical features other than fast breathing which might help us in earliest diagnosis of pneumonia in children with diarrhea Thus, the objective of our study was to identify other contributing clinical features that may independently help for early diagnosis of pneumonia in diarrheal children who present with age specific fast breathing. This was an unmatched case-control study. Diarrheal children aged 0-59 months, admitted to Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) during January 2014 to December 2014 having age specific fast breathing (<2 month ≥60 breath/min, 2-11 months ≥50 breaths/min, >11-59 months ≥40 breaths/min) were studied. The study children with clinical and radiological pneumonia constituted the cases (n = 276) and those without pneumonia constituted the controls (n = 446). Comparison of clinical features and outcomes between the cases and the controls was made. The distribution of acidosis among the cases and the controls was comparable (35% vs. 41%, p = 0.12). The cases had proportionately higher deaths compared to the controls, however, the difference was not statistically significant (3% vs. 1%; p = 0.23). In logistic regression analysis after adjusting for potential confounders, the cases were independently associated with cough (OR = 62.19, 95% CI = 27.79-139.19; p<0.01) and chest wall indrawing (OR = 31.05, 95%CI = 13.43-71.82; p<0.01) and less often had severe

The progestin etonogestrel enhances the respiratory response to metabolic acidosis in newborn rats. Evidence for a mechanism involving supramedullary structures.

PubMed

Loiseau, Camille; Osinski, Diane; Joubert, Fanny; Straus, Christian; Similowski, Thomas; Bodineau, Laurence

2014-05-01

Central congenital hypoventilation syndrome is a neuro-respiratory disease characterized by the dysfunction of the CO2/H(+) chemosensitive neurons of the retrotrapezoid nucleus/parafacial respiratory group. A recovery of CO2/H(+) chemosensitivity has been observed in some central congenital hypoventilation syndrome patients coincidental with contraceptive treatment by a potent progestin, desogestrel (Straus et al., 2010). The mechanisms of this progestin effect remain unknown, although structures of medulla oblongata, midbrain or diencephalon are known to be targets for progesterone. In the present study, on ex vivo preparations of central nervous system of newborn rats, we show that acute exposure to etonogestrel (active metabolite of desogestrel) enhanced the increased respiratory frequency induced by metabolic acidosis via a mechanism involving supramedullary structures located in pontine, mesencephalic or diencephalic regions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of metabolic alkalosis on respiratory function in patients with chronic obstructive lung disease.

PubMed Central

Bear, R.; Goldstein, M.; Phillipson, E.; Ho, M.; Hammeke, M.; Feldman, R.; Handelsman, S.; Halperin, M.

1977-01-01

Eleven instances of a mixed acid-base disorder consisting of chronic respiratory acidosis and metabolic alkalosis were recognized in eight patients with chronic obstructive lung disease and carbon dioxide retention. Correction of the metabolic alkalosis led to substantial improvement in blood gas values and clinical symptoms. Patients with mixed chronic respiratory acidosis and metabolic alkalosis constitute a common subgroup of patients with chronic obstructive lung disease and carbon dioxide retention; these patients benefit from correction of the metabolic alkalosis. PMID:21028

Development and Resuscitation of a Sedated, Mature Male Miniature Swine Severe Hemorrhage Model

DTIC Science & Technology

2011-07-01

control. Results: Hemorrhage resulted in a characteristic hypotension and metabolic acidosis . Survival time for the control swine was 64 minutes...domestic swine4 and was characteristic of a hemorrhage- induced metabolic acidosis , with a decrease in blood HCO3, and BE and an increase in blood...Hammett M, Asher L, et al. Effects of bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine. Shock. 2005;24:145–152

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.

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.

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

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.

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.

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.

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.

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

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.

Glycolysis in energy metabolism during seizures.

PubMed

Yang, Heng; Wu, Jiongxing; Guo, Ren; Peng, Yufen; Zheng, Wen; Liu, Ding; Song, Zhi

2013-05-15

Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. However, how lactic acid provides energy for seizures and how it can participate in the termination of seizures remains unclear. We reviewed possible mechanisms of glycolysis involved in seizure onset. Results showed that lactic acid was involved in seizure onset and provided energy at early stages. As seizures progress, lactic acid reduces the pH of tissue and induces metabolic acidosis, which terminates the seizure. The specific mechanism of lactic acid-induced acidosis involves several aspects, which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1, inhibition of the N-methyl-D-aspartate receptor, activation of the acid-sensitive 1A ion channel, strengthening of the receptive mechanism of the inhibitory neurotransmitter γ-minobutyric acid, and changes in the intra- and extracellular environment.

Glycolysis in energy metabolism during seizures☆

PubMed Central

Yang, Heng; Wu, Jiongxing; Guo, Ren; Peng, Yufen; Zheng, Wen; Liu, Ding; Song, Zhi

2013-01-01

Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. However, how lactic acid provides energy for seizures and how it can participate in the termination of seizures remains unclear. We reviewed possible mechanisms of glycolysis involved in seizure onset. Results showed that lactic acid was involved in seizure onset and provided energy at early stages. As seizures progress, lactic acid reduces the pH of tissue and induces metabolic acidosis, which terminates the seizure. The specific mechanism of lactic acid-induced acidosis involves several aspects, which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1, inhibition of the N-methyl-D-aspartate receptor, activation of the acid-sensitive 1A ion channel, strengthening of the receptive mechanism of the inhibitory neurotransmitter γ-minobutyric acid, and changes in the intra- and extracellular environment. PMID:25206426

Amelogenesis Imperfecta with Distal Renal Tubular Acidosis: A Novel Syndrome?

PubMed

Misgar, R A; Hassan, Z; Wani, A I; Bashir, M I

2017-01-01

Amelogenesis imperfecta (AI) is a heterogeneous group of inherited dental enamel defects. It has rarely been reported in association with multiorgan syndromes and metabolic disorders. The metabolic disorders that have been reported in association with AI include hypocalciuria, impaired urinary concentrating ability, and Bartter-like syndrome. In literature, only three cases of AI and distal renal tubular acidosis (dRTA) have been described: two cases in adults and a solitary case in the pediatric age group. Here, we report a child with AI presenting with dRTA; to the best of our knowledge, our reported case is the only second such case in pediatric age group. Our case highlights the importance of recognizing the possibility of renal abnormalities in patients with AI as it will affect the long-term prognosis.

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.

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.

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.

Intrapartum fetal heart rate monitoring: evaluation of a standardized system of interpretation for prediction of metabolic acidosis at delivery and neonatal neurological morbidity.

PubMed

Soncini, Emanuele; Paganelli, Simone; Vezzani, Cristina; Gargano, Giancarlo; Giovanni Battista, La Sala

2014-09-01

To assess the ability of the intrapartum fetal heart rate interpretation system developed in 2008 by the National Institute of Child Health and Human Development (NICHD) to predict fetal metabolic acidosis at delivery and neonatal neurological morbidity. We analyzed the intrapartum fetal heart rate tracings of 314 singleton fetuses at ≥ 37 weeks using the NICHD three-tier system of interpretation: Category I (normal), Category II (indeterminate) and Category III (abnormal). Category II was further divided into Category IIA, with moderate fetal heart rate variability or accelerations, and Category IIB, with minimal/absent fetal heart rate variability and no accelerations. The presence and duration of the different patterns were compared with several clinical neonatal outcomes and with umbilical artery acid-base balance at birth. The mean values of pH and base excess decreased proportionally as tracings worsened (p < 0.001). The duration of at least 30 min for Category III tracings was highly predictive of a pH <7.00 and a base excess ≤-12 mmol/L. The same was true for the duration of Category IIB tracings that lasted for at least 50 min. Our study demonstrates that the interpretation of fetal heart rate tracings based on a strictly standardized system is closely associated with umbilical artery acid-base status at delivery.

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.

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.

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.

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

Anesthetic Management of Mitochondrial Encephalopathy With Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome) in a High-Risk Pregnancy: A Case Report.

PubMed

Bell, Josh D; Higgie, Kushlin; Joshi, Mital; Rucker, Joshua; Farzi, Sahar; Siddiqui, Naveed

2017-07-15

MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like symptoms) is a rare and complex mitochondrial disorder. We present the in-hospital course of a 36-year-old gravida 2, para 0 with MELAS syndrome and severe preeclampsia, complicated by hyponatremia, hyperkalemia, and diabetes. A retained placenta with postpartum hemorrhage required urgent instrumental delivery under spinal anesthesia, transfusion, and intensive care unit admission for pulmonary edema, effusions, and atelectasis. Postpartum endometritis and sepsis also were encountered. This is to our knowledge the first case report of obstetric complications in MELAS syndrome and highlights the salient metabolic sequelae of this syndrome.

Diagnosis and Management of Rumen Acidosis and Bloat in Feedlots.

PubMed

Meyer, Nathan F; Bryant, Tony C

2017-11-01

Ruminal acidosis and ruminal bloat represent the most common digestive disorders in feedlot cattle. Ruminants are uniquely adapted to digest and metabolize a large range of feedstuffs. Although cattle have the ability to handle various feedstuffs, disorders associated with altered ruminal fermentation can occur. Proper ruminal microorganism adaptation and a consistent substrate (ration) help prevent digestive disorders. Feed bunk management, sufficient ration fiber, consistent feed milling, and appropriate response to abnormal weather are additional factors important in prevention of digestive disorders. When digestive disorders are suspected, timely diagnosis is imperative. Copyright © 2017 Elsevier Inc. All rights reserved.

Very Low-Protein Diet (VLPD) Reduces Metabolic Acidosis in Subjects with Chronic Kidney Disease: The "Nutritional Light Signal" of the Renal Acid Load.

PubMed

Di Iorio, Biagio Raffaele; Di Micco, Lucia; Marzocco, Stefania; De Simone, Emanuele; De Blasio, Antonietta; Sirico, Maria Luisa; Nardone, Luca

2017-01-17

Metabolic acidosis is a common complication of chronic kidney disease; current guidelines recommend treatment with alkali if bicarbonate levels are lower than 22 mMol/L. In fact, recent studies have shown that an early administration of alkali reduces progression of CKD. The aim of the study is to evaluate the effect of fruit and vegetables to reduce the acid load in CKD. We conducted a case-control study in 146 patients who received sodium bicarbonate. Of these, 54 patients assumed very low-protein diet (VLPD) and 92 were controls (ratio 1:2). We calculated every three months the potential renal acid load (PRAL) and the net endogenous acid production (NEAP), inversely correlated with serum bicarbonate levels and representing the non-volatile acid load derived from nutrition. Un-paired T -test and Chi-square test were used to assess differences between study groups at baseline and study completion. Two-tailed probability values ≤0.05 were considered statistically significant. At baseline, there were no statistical differences between the two groups regarding systolic blood pressure (SBP), diastolic blood pressure (DBP), protein and phosphate intake, urinary sodium, potassium, phosphate and urea nitrogen, NEAP, and PRAL. VLPD patients showed at 6 and 12 months a significant reduction of SBP ( p < 0.0001), DBP ( p < 0.001), plasma urea ( p < 0.0001) protein intake ( p < 0.0001), calcemia ( p < 0.0001), phosphatemia ( p < 0.0001), phosphate intake ( p < 0.0001), urinary sodium ( p < 0.0001), urinary potassium ( p < 0.002), and urinary phosphate ( p < 0.0001). NEAP and PRAL were significantly reduced in VLPD during follow-up. VLPD reduces intake of acids; nutritional therapy of CKD, that has always taken into consideration a lower protein, salt, and phosphate intake, should be adopted to correct metabolic acidosis, an important target in the treatment of CKD patients. We provide useful indications regarding acid load of food and drinks-the "acid load dietary traffic

Value of point-of-care ketones in assessing dehydration and acidosis in children with gastroenteritis.

PubMed

Levy, Jason A; Waltzman, Mark; Monuteaux, Michael C; Bachur, Richard G

2013-11-01

Children with gastroenteritis often develop dehydration with metabolic acidosis. Serum ketones are frequently elevated in this population. The goal was to determine the relationship between initial serum ketone concentration and both the degree of dehydration and the magnitude of acidosis. This was a secondary analysis of a prospective trial of crystalloid administration for rapid rehydration. Children 6 months to 6 years of age with gastroenteritis and dehydration were enrolled. A point-of-care serum ketone (beta-hydroxybutyrate) concentration was obtained at the time of study enrollment. The relationship between initial serum ketone concentration and a prospectively assigned and previously validated clinical dehydration score, and serum bicarbonate concentration, was analyzed. A total of 188 patients were enrolled. The median serum ketone concentration was elevated at 3.1 mmol/L (interquartile range [IQR] = 1.2 to 4.6 mmol/L), and the median dehydration score was consistent with moderate dehydration. A significant positive relationship was found between serum ketone concentration and the clinical dehydration score (Spearman's rho = 0.22, p = 0.003). Patients with moderate dehydration had a higher median serum ketone concentration than those with mild dehydration (3.6 mmol/L vs. 1.4 mmol/L, p = 0.007). Additionally, the serum ketone concentration was inversely correlated with serum bicarbonate concentration (ρ = -0.26, p < 0.001). Children with gastroenteritis and dehydration have elevated serum ketone concentrations that correlate with both degree of dehydration and magnitude of metabolic acidosis. Point-of-care serum ketone measurement may be a useful tool to inform management decisions at the point of triage or in the initial evaluation of children with gastroenteritis and dehydration. © 2013 by the Society for Academic Emergency Medicine.

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

Metabolic alkalosis in adults with stable cystic fibrosis.

PubMed

Al-Ghimlas, Fahad; Faughnan, Marie E; Tullis, Elizabeth

2012-01-01

The frequency of metabolic alkalosis among adults with stable severe CF-lung disease is unknown. Retrospective chart review. Fourteen CF and 6 COPD (controls) patients were included. FEV1 was similar between the two groups. PaO2 was significantly higher in the COPD (mean ± 2 SD is 72.0 ± 6.8 mmHg,) than in the CF group (56.1 ± 4.1 mmHg). The frequency of metabolic alkalosis in CF patients (12/14, 86%) was significantly greater (p=0.04) than in the COPD group (2/6, 33%). Mixed respiratory acidosis and metabolic alkalosis was evident in 4 CF and 1 COPD patients. Primary metabolic alkalosis was observed in 8 CF and none of the COPD patients. One COPD patient had respiratory and metabolic alkalosis. Metabolic alkalosis is more frequent in stable patients with CF lung disease than in COPD patients. This might be due to defective CFTR function with abnormal electrolyte transport within the kidney and/ or gastrointestinal tract.

Very Low-Protein Diet (VLPD) Reduces Metabolic Acidosis in Subjects with Chronic Kidney Disease: The “Nutritional Light Signal” of the Renal Acid Load

PubMed Central

Di Iorio, Biagio Raffaele; Di Micco, Lucia; Marzocco, Stefania; De Simone, Emanuele; De Blasio, Antonietta; Sirico, Maria Luisa; Nardone, Luca

2017-01-01

Background: Metabolic acidosis is a common complication of chronic kidney disease; current guidelines recommend treatment with alkali if bicarbonate levels are lower than 22 mMol/L. In fact, recent studies have shown that an early administration of alkali reduces progression of CKD. The aim of the study is to evaluate the effect of fruit and vegetables to reduce the acid load in CKD. Methods: We conducted a case-control study in 146 patients who received sodium bicarbonate. Of these, 54 patients assumed very low-protein diet (VLPD) and 92 were controls (ratio 1:2). We calculated every three months the potential renal acid load (PRAL) and the net endogenous acid production (NEAP), inversely correlated with serum bicarbonate levels and representing the non-volatile acid load derived from nutrition. Un-paired T-test and Chi-square test were used to assess differences between study groups at baseline and study completion. Two-tailed probability values ≤0.05 were considered statistically significant. Results: At baseline, there were no statistical differences between the two groups regarding systolic blood pressure (SBP), diastolic blood pressure (DBP), protein and phosphate intake, urinary sodium, potassium, phosphate and urea nitrogen, NEAP, and PRAL. VLPD patients showed at 6 and 12 months a significant reduction of SBP (p < 0.0001), DBP (p < 0.001), plasma urea (p < 0.0001) protein intake (p < 0.0001), calcemia (p < 0.0001), phosphatemia (p < 0.0001), phosphate intake (p < 0.0001), urinary sodium (p < 0.0001), urinary potassium (p < 0.002), and urinary phosphate (p < 0.0001). NEAP and PRAL were significantly reduced in VLPD during follow-up. Conclusion: VLPD reduces intake of acids; nutritional therapy of CKD, that has always taken into consideration a lower protein, salt, and phosphate intake, should be adopted to correct metabolic acidosis, an important target in the treatment of CKD patients. We provide useful indications regarding acid load of food and drinks�

Effects of nutritionally induced metabolic acidosis with or without glutamine infusion on acid-base balance, plasma amino acids, and plasma nonesterified fatty acids in sheep.

PubMed

Odongo, N E; Greenwood, S L; Or-Rashid, M M; Radford, D; Alzahal, O; Shoveller, A K; Lindinger, M I; Matthews, J C; McBride, B W

2009-03-01

This study characterized the effects of nutritionally induced metabolic acidosis with or without Gln infusion on acid-base balance, plasma AA, and plasma NEFA in sheep. In a randomized complete block design with a 2 x 2 factorial arrangement of treatments, 24 fully fleeced sheep (Rideau-Arcott, 63.6 +/- 5.9 kg of BW) were fed a control supplement (CS; 300 g/d of canola meal) or an acidosis supplement (AS; 300 g/d of NutriChlor; HCl-treated canola meal), offered twice daily at 0700 and 1100 h. Sheep were infused at 1400 h daily with 0.3 g of L-glutamine per kg of BW or saline via jugular vein catheters for 7 d. The sheep were individually housed and limit-fed a basal diet of dehydrated alfalfa pellets (1.75 kg/d; 90% DM, 22% CP, and 1.2 Mcal of NE(g)/kg on a DM basis) offered twice daily at 1000 and 1300 h. Blood and urine was sampled daily between 1100 and 1130 h, and blood samples were analyzed for hematocrit, plasma pH, gases, strong ions, AA, and NEFA, whereas urine was analyzed for pH. The AS reduced (P < 0.01) DMI, urine and plasma pH, blood urea, partial pressure of CO(2), strong ion difference, and plasma HCO(3)(-), and increased (P < 0.01) plasma K(+), Ca(2+), and Cl(-). The AS with saline infusion increased (P

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

Metabolic Acidosis Increases Intracellular Calcium in Bone Cells Through Activation of the Proton Receptor OGR1

PubMed Central

Frick, Kevin K; Krieger, Nancy S; Nehrke, Keith; Bushinsky, David A

2009-01-01

Metabolic acidosis increases urine Ca without increasing intestinal absorption, leading to bone Ca loss. It is unclear how bone cells detect the increase in proton concentration. To determine which G protein-coupled proton sensing receptors are expressed in bone, PCR was performed, and products were detected for OGR1, TDAG8, G2A, and GPR4. We tested the hypothesis that the G protein-coupled proton sensor, OGR1, is an H+-sensing receptor in bone. To determine whether acid-induced bone resorption involves OGR1, we incubated mouse calvariae in neutral pH (NTL) or acidic (MET) medium ± the OGR1 inhibitor CuCl2. CuCl2 decreased MET-induced Ca efflux. We used fluorescent imaging of perfused bone cells to determine whether MET increases Cai. Perfusion with MET induced a rapid, flow-independent, increase in Cai in individual bone cells. To determine whether transfection of OGR1 into a heterologous cell type would increase Cai in response to H+, we perfused Chinese hamster ovary (CHO) cells transfected with mouse OGR1 cDNA. Perfusion with MET induced a rapid increase in Cai in OGR1-transfected CHO cells. These data indicate that OGR1 induces an increase in Cai in response to MET and is a prime candidate for an osteoblast proton sensor. PMID:18847331

Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1.

PubMed

Frick, Kevin K; Krieger, Nancy S; Nehrke, Keith; Bushinsky, David A

2009-02-01

Metabolic acidosis increases urine Ca without increasing intestinal absorption, leading to bone Ca loss. It is unclear how bone cells detect the increase in proton concentration. To determine which G protein-coupled proton sensing receptors are expressed in bone, PCR was performed, and products were detected for OGR1, TDAG8, G2A, and GPR4. We tested the hypothesis that the G protein-coupled proton sensor, OGR1, is an H(+)-sensing receptor in bone. To determine whether acid-induced bone resorption involves OGR1, we incubated mouse calvariae in neutral pH (NTL) or acidic (MET) medium +/- the OGR1 inhibitor CuCl(2). CuCl(2) decreased MET-induced Ca efflux. We used fluorescent imaging of perfused bone cells to determine whether MET increases Ca(i). Perfusion with MET induced a rapid, flow-independent, increase in Ca(i) in individual bone cells. To determine whether transfection of OGR1 into a heterologous cell type would increase Ca(i) in response to H(+), we perfused Chinese hamster ovary (CHO) cells transfected with mouse OGR1 cDNA. Perfusion with MET induced a rapid increase in Ca(i) in OGR1-transfected CHO cells. These data indicate that OGR1 induces an increase in Ca(i) in response to MET and is a prime candidate for an osteoblast proton sensor.

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

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.

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

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.

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.

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.

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

[A case of favourable outcome of the treatment of extremely severe acute poisoning with methanol].

PubMed

Batotsyrenov, B V; Livanov, G A; Vasil'ev, S A; Fedorov, A V; Antrianov, A Iu

2013-01-01

A case of favourable outcome of the treatment of extremely severe acute poisoning after prolonged exposure to lethal doses of methanol is reported. The complex treatment included urgent and effective elimination of the poison (multiple gastric lavage, hemodialysis), antidote therapy (administration of ethanol), correction of decompensated metabolic acidosis (alkali therapy and infusion therapy with reamberin). These measures had beneficial effect on the clinical course of poisoning and ensured its favourable outcome.

Severe hypoglycemic encephalopathy due to hypoallergenic formula in an infant.

PubMed

Ogawa, Erika; Ishige, Mika; Takahashi, Yuno; Kodama, Hiroko; Fuchigami, Tatsuo; Takahashi, Shori

2016-08-01

A 7-month-old girl was brought to hospital due to vomiting. Upon admission, she was in a convulsive state and stupor with extremely low blood glucose. Head computed tomography showed brain edema, and comprehensive treatment for acute encephalopathy was initiated immediately. Severe hypoglycemia, metabolic acidosis, elevation of ammonia and serum transaminases and creatine kinase suggested metabolic decompensation. Infusion of a high-glucose solution containing vitamins, biotin, and l-carnitine resolved the metabolic crisis quickly, but brain damage was irreversible. She was found to have been fed exclusively on a hypoallergenic formula (HF) for 7 months, although she was found later to be non-allergic. Evidence of inborn metabolic diseases was absent, therefore biotin deficiency and carnitine deficiency were concluded to be a consequence of reliance on a HF for a prolonged period. Health-care professionals should warn parents of the consequences of using HF. © 2016 Japan Pediatric Society.

Fecal Transplantation Successfully Treats Recurrent D-Lactic Acidosis in a Child With Short Bowel Syndrome.

PubMed

Davidovics, Zev H; Vance, Katherine; Etienne, Nancy; Hyams, Jeffrey S

2017-07-01

D-lactic acidosis can occur in patients with short bowel syndrome (SBS) when excessive malabsorbed carbohydrate (CHO) enters the colon and is metabolized by colonic bacteria to D-lactate. D-lactate can be absorbed systemically, and increased serum levels are associated with central nervous system toxicity manifested by confusion, ataxia, and slurred speech. Current therapy, usually directed toward suppressing intestinal bacterial overgrowth and limiting ingested CHO, is not always successful. Fecal transplantation, the infusion of donor feces into a recipient's intestinal tract, has been used for decades to treat recurrent Clostridium difficile infection, and case reports document its use in the successful treatment of constipation, diarrhea, and abdominal pain. The exact mechanism of action is unknown, but it is surmised that the alteration of the intestinal microbiome, as well as the reintroduction of potential beneficial microbes, helps mediate disease. Here we present the case of a child with SBS and recurrent, debilitating D-lactic acidosis, which was successfully treated with fecal transplantation.

Nutritional and metabolic diseases involving the nervous system.

PubMed

Kopcha, M

1987-03-01

This article will discuss eight diseases that alter normal nervous system function: hypovitaminosis A, water deprivation/salt toxicity, ammonia toxicosis, hypomagnesemia, hypocalcemia, nervous ketosis, hepatoencephalopathy, and rumen metabolic acidosis.

Severe metabolic alkalosis: a case report.

PubMed Central

Javaheri, S; Nardell, E A

1981-01-01

A 45-year-old man who was admitted with nausea, vomiting, and abdominal pain was found to have severe metabolic alkalosis, with a PaCO2 of 11.4kPa (85.5 mm Hg), PaO2 of 5.8 kPa (43.5 mm Hg), pH of 7.61, and plasma bicarbonate concentration of 82.0 mmol/l. He was treated with oxygen, intravenous physiological saline, and phenytoin and improved within 48 hours. Radiographs showed gastric outlet obstruction secondary to peptic ulcer, which was treated by surgery. Though sever, the rise in carbon dioxide concentration in this patient was probably lifesaving. The PaCO2 was therefore allowed to fall gradually as the alkalosis was treated. The return of both PaCO2 and plasma bicarbonate values to normal in parallel suggests that hypoventilation compensated for the metabolic alkalosis and emphasises the importance of conservative treatment in cases of metabolic alkalosis. PMID:6794744

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.

Metabolic Alkalosis in Adults with Stable Cystic Fibrosis

PubMed Central

Al-Ghimlas, Fahad; Faughnan, Marie E; Tullis, Elizabeth

2012-01-01

Background: The frequency of metabolic alkalosis among adults with stable severe CF-lung disease is unknown. Methods: Retrospective chart review. Results: Fourteen CF and 6 COPD (controls) patients were included. FEV1 was similar between the two groups. PaO2 was significantly higher in the COPD (mean ± 2 SD is 72.0 ± 6.8 mmHg,) than in the CF group (56.1 ± 4.1 mmHg). The frequency of metabolic alkalosis in CF patients (12/14, 86%) was significantly greater (p=0.04) than in the COPD group (2/6, 33%). Mixed respiratory acidosis and metabolic alkalosis was evident in 4 CF and 1 COPD patients. Primary metabolic alkalosis was observed in 8 CF and none of the COPD patients. One COPD patient had respiratory and metabolic alkalosis. Conclusions: Metabolic alkalosis is more frequent in stable patients with CF lung disease than in COPD patients. This might be due to defective CFTR function with abnormal electrolyte transport within the kidney and/ or gastrointestinal tract. PMID:22905070

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.

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

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.

Prevention of complications in glycogen storage disease type Ia with optimization of metabolic control.

PubMed

Dambska, M; Labrador, E B; Kuo, C L; Weinstein, D A

2017-08-01

Prior to 1971, type Ia glycogen storage disease was marked by life-threatening hypoglycemia, lactic acidosis, severe failure to thrive, and developmental delay. With the introduction of continuous feeds in the 1970s and cornstarch in the 1980s, the prognosis improved, but complications almost universally developed. Changes in the management of type Ia glycogen storage disease have resulted in improved metabolic control, and this manuscript reviews the increasing evidence that complications can be delayed or prevented with optimal metabolic control as previously was seen in diabetes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Increased feeding frequency increased milk fat yield and may reduce the severity of subacute ruminal acidosis in higher-risk cows.

PubMed

Macmillan, K; Gao, X; Oba, M

2017-02-01

The objectives of this study were to determine whether feeding behavior is different between cows at higher or lower risk for subacute ruminal acidosis (SARA) and whether increasing feeding frequency could be used to reduce the severity of SARA in higher-risk cows. In preliminary studies, 16 ruminally cannulated lactating cows were fed high-grain diets once per day to increase the risk of SARA. After a 17-d diet adaptation, ruminal pH was measured every 30 s over 24 h. Cows were classified as higher-risk (n = 7) or lower-risk (n = 9) for SARA based on an acidosis index (area of pH <5.8/dry matter intake). Feeding behavior was recorded every 5 min over the same 24 h. The 24-h observation period was analyzed in 3 periods of 8 h after feeding. Although there was no significant difference in overall dry matter intake, higher-risk cows spent more time eating in the first 8-h period after feeding than lower-risk cows (186 vs. 153 min) and less time eating in the third 8-h period (19 vs. 43 min). In the primary experiment, 8 ruminally cannulated lactating cows were fed a high-grain diet once per day (1×; 0800 h) or 3 times per day (3×; 0800, 1500, and 2000 h) in a crossover design with 21-d periods (16 d of treatment adaptation and 5 d of data collection). Rumen pH and feeding behavior were measured over 72 h. Behavior data were summarized separately for the 3 periods (0800 to 1500, 1500 to 2200, and 2200 to 0800 h). Four cows were categorized as higher-risk and 4 as lower-risk, based on their acidosis index. The 3× feeding reduced eating time between 0800 and 1500 h (99 vs. 145 min) and increased eating time between 2200 and 0800 h (76 vs. 43 min) for all cows, regardless of category, compared with 1× feeding. For higher-risk cows, 3× feeding reduced the area below pH 5.8 (51 vs. 98 pH × min/d), but it did not affect rumen pH for the lower-risk cows. Milk yield was not different between groups, but 3× feeding increased milk fat yield (1.22 vs. 1.08 kg/d) for all

Fatal neonatal encephalopathy and lactic acidosis caused by a homozygous loss-of-function variant in COQ9.

PubMed

Danhauser, Katharina; Herebian, Diran; Haack, Tobias B; Rodenburg, Richard J; Strom, Tim M; Meitinger, Thomas; Klee, Dirk; Mayatepek, Ertan; Prokisch, Holger; Distelmaier, Felix

2016-03-01

Coenzyme Q10 (CoQ10) has an important role in mitochondrial energy metabolism by way of its functioning as an electron carrier in the respiratory chain. Genetic defects disrupting the endogenous biosynthesis pathway of CoQ10 may lead to severe metabolic disorders with onset in early childhood. Using exome sequencing in a child with fatal neonatal lactic acidosis and encephalopathy, we identified a homozygous loss-of-function variant in COQ9. Functional studies in patient fibroblasts showed that the absence of the COQ9 protein was concomitant with a strong reduction of COQ7, leading to a significant accumulation of the substrate of COQ7, 6-demethoxy ubiquinone10. At the same time, the total amount of CoQ10 was severely reduced, which was reflected in a significant decrease of mitochondrial respiratory chain succinate-cytochrome c oxidoreductase (complex II/III) activity. Lentiviral expression of COQ9 restored all these parameters, confirming the causal role of the variant. Our report on the second COQ9 patient expands the clinical spectrum associated with COQ9 variants, indicating the importance of COQ9 already during prenatal development. Moreover, the rescue of cellular CoQ10 levels and respiratory chain complex activities by CoQ10 supplementation points to the importance of an early diagnosis and immediate treatment.

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.

Strong ion and weak acid analysis in severe preeclampsia: potential clinical significance.

PubMed

Ortner, C M; Combrinck, B; Allie, S; Story, D; Landau, R; Cain, K; Dyer, R A

2015-08-01

The influence of common disturbances seen in preeclampsia, such as changes in strong ions and weak acids (particularly albumin) on acid-base status, has not been fully elucidated. The aims of this study were to provide a comprehensive acid-base analysis in severe preeclampsia and to identify potential new biological predictors of disease severity. Fifty women with severe preeclampsia, 25 healthy non-pregnant- and 46 healthy pregnant controls (26-40 weeks' gestation), were enrolled in this prospective case-control study. Acid-base analysis was performed by applying the physicochemical approach of Stewart and Gilfix. Mean [sd] base excess was similar in preeclamptic- and healthy pregnant women (-3.3 [2.3], and -2.8 [1.5] mEq/L respectively). In preeclampsia, there were greater offsetting contributions to the base excess, in the form of hyperchloraemia (BE(Cl) -2 [2.3] vs -0.4 [2.3] mEq/L, P<0.001) and hypoalbuminaemia (BE(Alb) 3.6 [1] vs 2.1 [0.8] mEq/L, P<0.001). In preeclampsia, hypoalbuminaemic metabolic alkalosis was associated with a non-reassuring/abnormal fetal heart tracing (P<0.001). Quantitative analysis in healthy pregnancy revealed respiratory and hypoalbuminaemic alkalosis that was metabolically offset by acidosis, secondary to unmeasured anions and dilution. While the overall base excess in severe preeclampsia is similar to that in healthy pregnancy, preeclampsia is associated with a greater imbalance offsetting hypoalbuminaemic alkalosis and hyperchloraemic acidosis. Rather than the absolute value of base excess, the magnitude of these opposing contributors may be a better indicator of the severity of this disease. Hypoalbuminaemic alkalosis may also be a predictor of fetal compromise. clinicaltrials.gov: NCT 02164370. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A patient with acute liver failure and extreme hypoglycaemia with lactic acidosis who was not in a coma: causes and consequences of lactate-protected hypoglycaemia.

PubMed

Oldenbeuving, G; McDonald, J R; Goodwin, M L; Sayilir, R; Reijngoud, D J; Gladden, L B; Nijsten, M W N

2014-07-01

Lactate can substitute for glucose as a metabolic substrate. We report a patient with acute liver failure who was awake despite a glucose level of 0.7 mmol/l with very high lactate level of 25 mmol/l. The hypoglycaemia+hyperlactataemia combination may be considered paradoxical since glucose is the main precursor of lactate and lactate is reconverted into glucose by the Cori cycle. Literature relevant to the underlying mechanism of combined deep hypoglycaemia and severe hyperlactataemia was assessed. We also assessed the literature for evidence of protection against deep hypoglycaemia by hyperlactataemia. Four syndromes demonstrating hypoglycaemia+hyperlactataemia were found: 1) paracetamol-induced acute liver failure, 2) severe malaria, 3) lymphoma and 4) glucose-6-phosphatase deficiency. An impaired Cori cycle is a key component in all of these metabolic states. Apparently the liver, after exhausting its glycogen stores, loses the gluconeogenic pathway to generate glucose and thereby its ability to remove lactate as well. Several patients with lactic acidosis and glucose levels below 1.7 mmol/l who were not in a coma have been reported. These observations and other data coherently indicate that lactate-protected hypoglycaemia is, at least transiently, a viable state under experimental and clinical conditions. Severe hypoglycaemia+hyperlactataemia reflects failure of the gluconeogenic pathway of lactate metabolism. The existence of lactate-protected hypoglycaemia implies that patients who present with this metabolic state should not automatically be considered to have sustained irreversible brain damage. Moreover, therapies that aim to achieve hypoglycaemia might be feasible with concomitant hyperlactataemia.

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.

[Severe rhabdomyolysis secondary to severe hypernatraemic dehydration].

PubMed

Mastro-Martínez, Ignacio; Montes-Arjona, Ana María; Escudero-Lirio, Margarita; Hernández-García, Bárbara; Fernández-Cantalejo Padial, José

2015-01-01

Rhabdomyolysis is a rare paediatric condition. The case is presented of a patient in whom this developed secondary to severe hypernatraemic dehydration following acute diarrhoea. Infant 11 months of age who presented with vomiting, fever, diarrhoea and anuria for 15 hours. Parents reported adequate preparation of artificial formula and oral rehydration solution. He was admitted with malaise, severe dehydration signs and symptoms, cyanosis, and low reactivity. The laboratory tests highlighted severe metabolic acidosis, hypernatraemia and pre-renal kidney failure (Sodium [Na] plasma 181 mEq/L, urine density> 1030). He was managed in Intensive Care Unit with gradual clinical and renal function improvement. On the third day, slight axial hypotonia and elevated cell lysis enzymes (creatine phosphokinase 75,076 IU/L) were observed, interpreted as rhabdomyolysis. He was treated with intravenous rehydration up to 1.5 times the basal requirements, and he showed a good clinical and biochemical response, being discharged 12 days after admission without motor sequelae. Severe hypernatraemia is described as a rare cause of rhabdomyolysis and renal failure. In critically ill patients, it is important to have a high index of suspicion for rhabdomyolysis and performing serial determinations of creatine phosphokinase for early detection and treatment. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

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

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.

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.

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.

Severe hyperkalemia as a complication of timolol, a topically applied beta-adrenergic antagonist

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swenson, E.R.

1986-06-01

Severe hyperkalemia occurred in a patient with radiation pneumonitis and glaucoma shortly after beginning prednisone therapy. There was no evidence of renal failure, diabetes, acidosis, increased potassium intake, or significant tissue trauma. Medications having adverse effects on potassium metabolism were considered, and the patient's use of timolol maleate eyedrops was discontinued. His serum potassium level normalized despite continuation of the prednisone therapy. He became hyperkalemic on rechallenge with timolol and normokalemic following its withdrawal. This case indicates that the potential for beta-blocker-induced hyperkalemia exists even with topical appreciation.

Devastating metabolic brain disorders of newborns and young infants.

PubMed

Yoon, Hyun Jung; Kim, Ji Hye; Jeon, Tae Yeon; Yoo, So-Young; Eo, Hong

2014-01-01

Metabolic disorders of the brain that manifest in the neonatal or early infantile period are usually associated with acute and severe illness and are thus referred to as devastating metabolic disorders. Most of these disorders may be classified as organic acid disorders, amino acid metabolism disorders, primary lactic acidosis, or fatty acid oxidation disorders. Each disorder has distinctive clinical, biochemical, and radiologic features. Early diagnosis is important both for prompt treatment to prevent death or serious sequelae and for genetic counseling. However, diagnosis is often challenging because many findings overlap and may mimic those of more common neonatal conditions, such as hypoxic-ischemic encephalopathy and infection. Ultrasonography (US) may be an initial screening method for the neonatal brain, and magnetic resonance (MR) imaging is the modality of choice for evaluating metabolic brain disorders. Although nonspecific imaging findings are common in early-onset metabolic disorders, characteristic patterns of brain involvement have been described for several disorders. In addition, diffusion-weighted images may be used to characterize edema during an acute episode of encephalopathy, and MR spectroscopy depicts changes in metabolites that may help diagnose metabolic disorders and assess response to treatment. Imaging findings, including those of advanced MR imaging techniques, must be closely reviewed. If one of these rare disorders is suspected, the appropriate biochemical test or analysis of the specific gene should be performed to confirm the diagnosis. ©RSNA, 2014.

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.

Effects of metabolic acidosis on intracellular pH responses in multiple cell types

PubMed Central

Salameh, Ahlam Ibrahim; Ruffin, Vernon A.

2014-01-01

Metabolic acidosis (MAc), a decrease in extracellular pH (pHo) caused by a decrease in [HCO3−]o at a fixed [CO2]o, is a common clinical condition and causes intracellular pH (pHi) to fall. Although previous work has suggested that MAc-induced decreases in pHi (ΔpHi) differ among cell types, what is not clear is the extent to which these differences are the result of the wide variety of methodologies employed by various investigators. In the present study, we evaluated the effects of two sequential MAc challenges (MAc1 and MAc2) on pHi in 10 cell types/lines: primary-cultured hippocampal (HCN) neurons and astrocytes (HCA), primary-cultured medullary raphé (MRN) neurons, and astrocytes (MRA), CT26 colon cancer, the C2C12 skeletal muscles, primary-cultured bone marrow-derived macrophages (BMDM) and dendritic cells (BMDC), Ink4a/ARF-null melanocytes, and XB-2 keratinocytes. We monitor pHi using ratiometric fluorescence imaging of 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein while imposing MAc: lowering (pHo) from 7.4 to 7.2 by decreasing [HCO3−]o from 22 to 14 mM at 5% CO2 for 7 min. After MAc1, we return cells to the control solution for 10 min and impose MAc2. Using our definition of MAc resistance [(ΔpHi/ΔpHo) ≤ 40%], during MAc1, ∼70% of CT26 and ∼50% of C2C12 are MAc-resistant, whereas the other cell types are predominantly MAc-sensitive. During MAc2, some cells adapt [(ΔpHi/ΔpHo)2 < (ΔpHi/ΔpHo)1], particularly HCA, C2C12, and BMDC. Most maintain consistent responses [(ΔpHi/ΔpHo)2 ≅ (ΔpHi/ΔpHo)1], and a few decompensate [(ΔpHi/ΔpHo)2>(ΔpHi/ΔpHo)1], particularly HCN, C2C12, and XB-2. Thus, responses to twin MAc challenges depend both on the individual cell and cell type. PMID:25209413

Chronic Metabolic Acidosis Activates Renal Tubular Sodium Chloride Cotransporter through Angiotension II-dependent WNK4-SPAK Phosphorylation Pathway

PubMed Central

Fang, Yu-Wei; Yang, Sung-Sen; Cheng, Chih-Jen; Tseng, Min-Hua; Hsu, Hui-Min; Lin, Shih-Hua

2016-01-01

The mechanism by which chronic metabolic acidosis (CMA) regulates sodium (Na+)-chloride (Cl−) cotransporter (NCC) in the renal distal convoluted tubules remains unexplored. We examined the role of STE20/SPS1-related proline/alanine-rich kinase (SPAK) and with-no-lysine kinase 4 (WNK4) on expression of NCC in mouse models of CMA. CMA was induced by NH4Cl in wild type mice (WTA mice), SPAK, and WNK4 knockout mice. The quantities of Ncc mRNA, expression of total NCC, phosphorylated (p)-NCC, SPAK and WNK4 in the kidneys as well as NCC inhibition with hydrochlorothiazide and Na+ balance were evaluated. Relative to WT mice, WTA mice had similar levels of Ncc mRNA, but increased expression of total and p-NCC, SPAK, and WNK4 and an exaggerated response to hydrochlorothiazide which could not be observed in SPAK or WNK4 knockout mice with CMA. In WTA mice, increased plasma renin activity, aldosterone and angiotensin II concentrations accompanied by a significantly negative Na+ balance. High Na+ diet abolished the enhanced NCC expression in WTA mice. Furthermore, an angiotensin II type 1 receptor blocker rather than a mineralocorticoid receptor antagonist exerted a marked inhibition on Na+ reabsorption and NCC phosphorylation in WTA mice. CMA increases WNK4-SPAK-dependent NCC phosphorylation and appears to be secondary to previous natriuresis with volume-dependent angiotensin II activation. PMID:26728390

Successful management of drug-induced hypercapnic acidosis with naloxone and noninvasive positive pressure ventilation.

PubMed

Agrafiotis, Michalis; Tryfon, Stavros; Siopi, Demetra; Chassapidou, Georgia; Galanou, Artemis; Tsara, Venetia

2015-02-01

A 74-year-old man was referred to our hospital due to deteriorating level of consciousness and desaturation. His Glasgow Coma Scale was 6, and his pupils were constricted but responded to light. Chest radiograph was negative for significant findings. Arterial blood gas evaluation on supplemental oxygen revealed severe acute on chronic respiratory acidosis: pH 7.15; PCO2, 133 mm Hg; PO2,64 mm Hg; and HCO3, 31 mmol/L. He regained full consciousness (Glasgow Coma Scale, 15) after receiving a 0.4 mg dose of naloxone, but because of persistent severe respiratory acidosis (pH 7.21; PCO2, 105 mm Hg), he was immediately commenced on noninvasive positive pressure ventilation (NIV) displaying a remarkable improvement in arterial blood gas values within the next few hours. However, in the days that followed, he remained dependent on NIV, and he was finally discharged on a home mechanical ventilation prescription. In cases of drug-induced respiratory depression, NIV should be regarded as an acceptable treatment, as it can provide ventilatory support without the increased risks associated with invasive mechanical ventilation.

[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.

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.

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

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.

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

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.

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

Evaluation of the systemic innate immune response and metabolic alterations of nonlactating cows with diet-induced subacute ruminal acidosis.

PubMed

Rodríguez-Lecompte, J C; Kroeker, A D; Ceballos-Márquez, A; Li, S; Plaizier, J C; Gomez, D E

2014-12-01

Subacute ruminal acidosis (SARA) increases lipopolysaccharide endotoxin in the rumen, which might translocate into the systemic circulation, triggering a cascade of clinical and immunological alterations. The objective of this study was to characterize the clinical immune and metabolic responses to ruminal-derived lipopolysaccharide in nonlactating cows induced with SARA using 2 challenges, a grain-based SARA challenge (GBSC) or an alfalfa-pellet SARA challenge (APSC). Six dry, nonlactating Holstein cows were used in a 3 × 3 Latin square arrangement of treatments with 4-wk experimental cycles. All cows received the control diet containing 70% forage and 30% mixed concentrates (dry matter basis) for 3 wk. In wk 4, cows received a control diet, GBSC (38% wheat-barley pellets, 32% other mixed concentrate, and 30% forages), or APSC (45% mixed concentrate, 32% alfalfa pellets, and 23% other forages). Total plasma proteins and immunology-related proteins, acute phase proteins, blood cells, serum chemistry, mRNA gene expression of peripheral blood cell surface markers, and selected proinflammatory cytokines were evaluated. Ruminal pH was lower in both groups with induced SARA compared with a control group. Ruminal endotoxins were higher in GBSC; however, plasma endotoxin was not detected in any study group. No significant differences in feed intake, rectal temperature, white blood cell counts, or differentials were found between control and SARA challenge groups; changes in glucose, urea, Ca, and Mg were observed in SARA groups. Total plasma proteins were lower in both SARA groups, and acute phase proteins were higher in GBSC. The expression of CD14, MD2, and TLR4 mRNA in peripheral blood leukocytes was not affected by SARA induction. The induction of SARA as a result of GBSC or APSC challenge was successful; however, LPS was not detected in plasma. Changes in clinical, metabolic, and inflammatory responses were not observed in the SARA-challenged cows, suggesting that

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

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

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.

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.

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

Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression

PubMed Central

Balkrishna, Sarojini; Bröer, Angelika; Welford, Scott M.; Hatzoglou, Maria; Bröer, Stefan

2015-01-01

Background Despite homeostatic pH regulation, systemic and cellular pH changes take place and strongly influence metabolic processes. Transcription of the glutamine transporter SNAT3 (Slc38a3) for instance is highly up-regulated in the kidney during metabolic acidosis to provide glutamine for ammonia production. Methods Slc38a3 promoter activity and messenger RNA stability were measured in cultured cells in response to different extracellular pH values. Results Up-regulation of SNAT3 mRNA was mediated both by the stabilization of its mRNA and by the up-regulation of gene transcription. Stabilisation of the mRNA involved a pH-response element, while enhanced transcription made use of a second pH-sensitive Sp1 binding site in addition to a constitutive Sp1 binding site. Transcriptional regulation dominated the early response to acidosis, while mRNA stability was more important for chronic adaptation. Tissue-specific expression of SNAT3, by contrast, appeared to be controlled by promoter methylation and histone modifications. Conclusions Regulation of SNAT3 gene expression by extracellular pH involves post-transcriptional and transcriptional mechanisms, the latter being distinct from the mechanisms that control the tissue-specific expression of the gene. PMID:24854847

Respiration of Chemodenervated Goats in Acute Metabolic Acidosis,

DTIC Science & Technology

1983-08-02

higher after CBx. We conclude that a respiratory adaptation to AMA does occur in goats deprived of peripheral chemoreceptors, and is probably mediated... respiratory adaptation to AMA does occur in goats deprived of peripheral chemoreceptors, and is probably mediated by the central chemo- receptors. Key...words: carotid bodies, CO2 rebreathing, CSF r’ INTRODUCTION Acid-base disturbances of primarily "metabolic" origin elicit respiratory compensation

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.

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.

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

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 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.

Stimulation of fibroblast growth factor 23 by metabolic acidosis requires osteoblastic intracellular calcium signaling and prostaglandin synthesis.

PubMed

Krieger, Nancy S; Bushinsky, David A

2017-10-01

Serum fibroblast growth factor 23 (FGF23) increases progressively in chronic kidney disease (CKD) and is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the factors regulating its production are not clear. Patients with CKD have decreased renal acid excretion leading to metabolic acidosis (MET). During MET, acid is buffered by bone with release of mineral calcium (Ca) and phosphate (P). MET increases intracellular Ca signaling and cyclooxygenase 2 (COX2)-induced prostaglandin production in the osteoblast, leading to decreased bone formation and increased bone resorption. We found that MET directly stimulates FGF23 in mouse bone organ cultures and primary osteoblasts. We hypothesized that MET increases FGF23 through similar pathways that lead to bone resorption. Neonatal mouse calvariae were incubated in neutral (NTL, pH = 7.44, Pco 2 = 38 mmHg, [HCO 3 - ] = 27 mM) or acid (MET, pH = 7.18, Pco 2 = 37 mmHg, [HCO 3 - ] = 13 mM) medium without or with 2-APB (50 μM), an inhibitor of intracellular Ca signaling or NS-398 (1 μM), an inhibitor of COX2. Each agent significantly inhibited MET stimulation of medium FGF23 protein and calvarial FGF23 RNA as well as bone resorption at 48 h. To exclude the potential contribution of MET-induced bone P release, we utilized primary calvarial osteoblasts. In these cells each agent inhibited MET stimulation of FGF23 RNA expression at 6 h. Thus stimulation of FGF23 by MET in mouse osteoblasts utilizes the same initial signaling pathways as MET-induced bone resorption. Therapeutic interventions directed toward correction of MET, especially in CKD, have the potential to not only prevent bone resorption but also lower FGF23 and perhaps decrease mortality. Copyright © 2017 the American Physiological Society.

Effect of a single dose of propofol and lack of dextrose administration in a child with mitochondrial disease: a case report.

PubMed

Mtaweh, Haifa; Bayır, Hülya; Kochanek, Patrick M; Bell, Michael J

2014-08-01

Propofol infusion syndrome is a recognized complication of prolonged propofol use in the pediatric population, but little is reported on other metabolic effects of propofol, especially in children with mitochondrial disorders. We report on a child with metabolic encephalopathy, lactic acidosis, and stroke-like syndrome who received a single dose of propofol for procedural sedation. The patient's initial presentation was consistent with a mild exacerbation of her underlying disease. She received a single dose of propofol and non-dextrose-containing fluids during a magnetic resonance imaging (MRI) study to rule out stroke and progressed to develop severe acidosis, neurologic deterioration, and cardiorespiratory compromise. This is the first case report of severe metabolic disturbances after a single dose of propofol administered for procedural sedation in a patient with metabolic encephalopathy, lactic acidosis, and stroke-like syndrome and it questions the safety of propofol and absence of dextrose infusions during an acute illness in patients with mitochondrial disorders. © The Author(s) 2013.

[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.

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.

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.

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

PubMed

Ha, Y-S; Hopper, K; Epstein, S E

2013-01-01

The incidence and causes of metabolic alkalosis in dogs and cats have not been fully investigated. To describe the incidence, nature, and etiology of metabolic alkalosis in dogs and cats undergoing blood gas analysis at a veterinary teaching hospital. Dogs and cats at a veterinary medical teaching hospital. Acid-base and electrolyte results for dogs and cats measured during a 13-month period were retrospectively collected from a computer database. Only the first measured (venous or arterial) blood gas analyzed in a single hospitalization period was included. Animals with a base excess above the reference range for the species were included. A total of 1,805 dogs and cats were included. Of these, 349 (19%) were identified as having an increased standardized base excess, 319 dogs and 30 cats. The mixed acid-base disorder of metabolic alkalosis with respiratory acidosis was the most common abnormality identified in both dogs and cats. Hypokalemia and hypochloremia were more common in animals with metabolic alkalosis compared to animals without metabolic alkalosis. The 4 most commonly identified underlying diseases were respiratory disease, gastrointestinal tract obstruction, furosemide administration, and renal disease. Metabolic alkalosis was less common than metabolic acidosis in the same population of animals. Evidence of contraction alkalosis was present in many patients in this study. Hypokalemia and hypochloremia were more frequent in patients with metabolic alkalosis and suggest the importance of evaluation of acid-base status in conjunction with serum electrolyte concentrations. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Liquid extracorporeal carbon dioxide removal: use of THAM (tris-hydroxymethyl aminomethane) coupled to hemofiltration to control hypercapnic acidosis in a porcine model of protective mechanical ventilation

PubMed Central

Tapia, Pablo; Lillo, Felipe; Soto, Dagoberto; Escobar, Leslie; Simon, Felipe; Hernández, Karina; Alegría, Leyla; Bruhn, Alejandro

2016-01-01

A promising approach to facilitate protective mechanical ventilation is the use of extracorporeal CO2 removal techniques. Several strategies based on membrane gas exchangers have been developed. However, these techniques are still poorly available. The goal of this study was to assess the efficacy and safety of THAM infusion coupled to hemofiltration for the management of hypercapnic acidosis. A severe respiratory acidosis was induced in seven anesthetized pigs. Five of them were treated with THAM 8-mmol·kg-1·h-1 coupled to hemofiltration (THAM+HF group) at 100 mL·kg-1·h-1. After 18-hours of treatment the THAM infusion was stopped but hemofiltration was kept on until 24-hours. The 2 other animals were treated with THAM but without hemofiltration. After 1-hour of treatment in THAM+HF, PaCO2 rapidly decreased from a median of 89.0 (IQR) (80.0, 98.0) to 71.3 (65.8, 82.0) mmHg (P<0.05), while pH increased from 7.12 (7.01, 7.15) to 7.29 (7.27, 7.30) (P<0.05). Thereafter PaCO2 remained stable between 60-70 mmHg, while pH increased above 7.4. After stopping THAM at 18 hours of treatment a profound rebound effect was observed with severe hypercapnic acidosis. The most important side effect we observed was hyperosmolality, which reached a maximum of 330 (328, 332) mOsm·kg H2O-1 at T18. The animals treated only with THAM developed severe hypercapnia, despite the fact that pH returned to normal values, and died after 12 hours. Control-group had an uneven evolution until the end of the experiment. A combined treatment with THAM coupled to hemofiltration may be an effective treatment to control severe hypercapnic acidosis. PMID:27648139

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.

Rumen microbial and fermentation characteristics are affected differently by acarbose addition during two nutritional types of simulated severe subacute ruminal acidosis in vitro.

PubMed

Wang, Yue; Liu, Junhua; Yin, Yuyang; Zhu, Weiyun; Mao, Shengyong

2017-10-01

Little information is available on whether or not the effect of an alpha-glucosidase inhibitor on the prevention of ruminal acidosis is influenced by the type of diet during ruminant feeding. This study was conducted to explore the effect of acarbose addition on the prevention of severe subacute ruminal acidosis induced by either cracked wheat or beet pulp in vitro. Cracked wheat and beet pulp were fermented in vitro by rumen microorganisms obtained from three dairy cows. When cracked wheat was used as the substrate and fermented for 24 h, compared with the control, acarbose addition decreased the concentrations of acetate, propionate, butyrate, total volatile fatty acids, and lactate (P < 0.05), while linearly increased the ratio of acetate to propionate, pH value, and the ammonia-nitrogen level (P < 0.05). Applying Illumina MiSeq sequencing of a fragment of the 16S rRNA gene revealed that the relative abundance of Firmicutes and Bacteroidetes as well as the ACE (abundance-based coverage estimator) value, Chao 1 value, and Shannon index increased significantly (P < 0.05), while there was a significant reduction (P < 0.05) in the relative abundance of Tenericutes as well as Proteobacteria after adding acarbose compared to the control. On the other hand, when beet pulp was used as the substrate, acarbose addition had no significant effects (P > 0.05) on the fermentation parameters and the Chao 1 value, the Shannon index, and the proportion of Firmicutes and Bacteroidetes. In general, these findings indicate that acarbose had more effects on ruminal fermentation when wheat was used as the substrate, whereas it exhibited little effect on ruminal fermentation when beet pulp was used as the substrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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.

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.

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

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

[Severe metabolic alkalosis following hypokalemia from a paraneoplastic Cushing syndrome].

PubMed

Dubé, L; Daenen, S; Kouatchet, A; Soltner, C; Alquier, P

2001-12-01

Metabolic alkalosis is frequently observed in critically ill patients. Etiologies are numerous but endocrinal causes are rare. We report a case of a patient with severe respiratory insufficiency, metabolic alkalosis and hypokalemia. The evolution was fatal. Further explorations revealed an ectopic Adrenocorticotropine Hormone syndrome. The initial tumor was probably a small cell lung carcinoma.

Comparison of the effects of intravenous administration of isotonic and hypertonic sodium bicarbonate solutions on venous acid-base status in dehydrated calves with strong ion acidosis.

PubMed

Coskun, Alparslan; Sen, Ismail; Guzelbektes, Hasan; Ok, Mahmut; Turgut, Kursat; Canikli, Sebnem

2010-05-15

OBJECTIVE-To compare the effects of IV administration of isotonic (1.3%) and hypertonic (8.4%) sodium bicarbonate (NaHCO(3)) solutions on acid-base status in dehydrated calves with strong ion (metabolic) acidosis. DESIGN-Randomized controlled clinical trial. ANIMALS-50 calves with diarrhea and severe dehydration. PROCEDURES-Calves were randomly assigned to receive isotonic NaHCO(3) solution (65 mL/kg [29.5 mL/lb], IV) over 3 hours (n = 30) or hypertonic NaHCO(3) solution (10 mL/kg [4.5 mL/lb], IV) over 20 minutes (20). Blood samples were collected at 0 hours (immediately prior to solution administration) and at 0.5, 1, 2, and 4 hours after administration began. Samples were submitted for blood gas analysis, serum biochemical analysis, and determination of blood Na(+), K(+), and Cl(-) concentrations and percentage change in plasma volume. RESULTS-Calves that received isotonic NaHCO(3) solution had an increase in venous blood pH, HCO(3) concentration, and base excess; a small, transient increase in Po(2); and no change in Pco(2) within 4 hours after administration began. Calves that received hypertonic NaHCO(3) solution had an immediate increase in venous blood pH, HCO(3) concentration, and base excess; a small, transient increase Pco(2); and no change in Po(2) within 0.5 hours after treatment began. Plasma volume increased to a greater extent following administration of isotonic solution than after administration of hypertonic solution. CONCLUSIONS AND CLINICAL RELEVANCE-IV administration of 8.4% NaHCO(3) solution in small volumes provided fast and effective improvement of severe acid-base abnormalities in calves with severe strong ion acidosis but did not improve hydration status as well as administration of a larger volume of isotonic NaHCO(3) solution.

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

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?

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

Renal tubular acidosis type IV in hyperkalaemic patients--a fairy tale or reality?

PubMed

Haas, Christian S; Pohlenz, Inga; Lindner, Ulrich; Muck, Philip M; Arand, Jovana; Suefke, Sven; Lehnert, Hendrik

2013-05-01

Hyperkalaemia is a common feature in hospitalized patients and often attributed to drugs antagonizing the renin-angiotensin-aldosterone system (RAAS) and/or acute kidney injury (AKI), despite significantly preserved glomerular filtration rate (GFR). The objective of this study was to determine the prevalence and role of renal tubular acidosis type IV (RTA IV) in the development of significant hyperkalaemia. A single-centre retrospective study. Patients admitted to a University Hospital over 12 months. Patients with a potassium value > 6·0 mm were identified. Clinical and laboratory data were revisited, and patients with a normal anion gap metabolic acidosis were evaluated for the existence of RTA IV. A total of 57 patients having significant hyperkalaemia (>6·0 mm) were identified. Twelve patients had end-stage renal disease, while 21 patients had solely AKI or progressive chronic renal failure. RTA IV was present in 24 patients (42%), of whom 71% had pre-existing renal insufficiency because of diabetic nephropathy or tubulointerstitial nephritis. All hyperkalaemic patients with urinary/serum electrolytes suggestive of RTA IV had evidence of AKI, but creatinine levels were significantly lower (P < 0·05), while the number of drugs antagonizing the RAAS was comparable. We demonstrated that RTA IV (i) is very common in patients with hyperkalaemia; (ii) should always be suspected in hyperkalaemic patients with only moderately impaired GFR; and (iii) may result in significant hyperkalaemia in the presence of both AKI and drugs antagonizing the RAAS. © 2012 Blackwell Publishing Ltd.

A prospective, observational registry of patients with severe sepsis: the Canadian Sepsis Treatment and Response Registry.

PubMed

Martin, Claudio M; Priestap, Fran; Fisher, Harold; Fowler, Robert A; Heyland, Daren K; Keenan, Sean P; Longo, Christopher J; Morrison, Teresa; Bentley, Diane; Antman, Neil

2009-01-01

To determine the location of acquisition, timing, and outcomes associated with severe sepsis in community and teaching hospital critical care units. Prospective, observational study. Twelve Canadian community and teaching hospital critical care units. All patients admitted between March 17, 2003, and November 30, 2004 to the study critical care units with at least a 24-hr length of stay or severe sepsis identified during the first 24 hrs. Daily monitoring for severe sepsis. We recorded data describing characteristics of patients, infections, systemic responses, and organ dysfunction. Severe sepsis occurred in 1238 patients (overall rate, 19.0%; range, 8.2%-35.3%). Hospital mortality was 38.1% (95% confidence interval [CI]: 35.4-40.8). Median intensive care unit length of stay was 10.3 days (interquartile range: 5.5, 17.9). Variables associated with mortality in multivariable analysis included age (odds ratio [OR] by decade 1.50; 95% CI: 1.36-1.65), acquisition location of severe sepsis (with community as the reference-hospital [OR: 1.69; CI: 1.16-2.46], early intensive care unit [OR: 2.15; CI: 1.42-3.25], late intensive care unit [OR: 2.65; CI: 1.82-3.87]), late intensive care unit (OR: 2.65; CI: 1.82-3.87), any comorbidity (OR: 1.42; CI: 1.04-1.93), chronic renal failure (OR: 2.03; CI: 1.10-3.76), oliguria (OR: 1.34; CI: 1.02-1.76), thrombocytopenia (OR: 2.12; CI: 1.43-3.13), metabolic acidosis (OR: 1.54; CI: 1.13-2.10), Multiple Organ Dysfunction Score (OR: 1.15; CI: 1.09-1.21) and Acute Physiology and Chronic Health Evaluation II predicted risk (OR: 3.75; CI: 2.08-6.76). These data confirm that sepsis is common and has high mortality in general intensive care unit populations. Our results can inform healthcare system planning and clinical study designs. Modifiable variables associated with worse outcomes, such as nosocomial infection (hospital acquisition), and metabolic acidosis indicate potential targets for quality improvement initiatives that could decrease

Resting and exercise energy metabolism in weight-reduced adults with severe obesity.

PubMed

Hames, Kazanna C; Coen, Paul M; King, Wendy C; Anthony, Steven J; Stefanovic-Racic, Maja; Toledo, Frederico G S; Lowery, Jolene B; Helbling, Nicole L; Dubé, John J; DeLany, James P; Jakicic, John M; Goodpaster, Bret H

2016-06-01

To determine effects of physical activity (PA) with diet-induced weight loss on energy metabolism in adults with severe obesity. Adults with severe obesity (n = 11) were studied across 6 months of intervention, then compared with controls with less severe obesity (n = 7) or normal weight (n = 9). Indirect calorimetry measured energy metabolism during exercise and rest. Markers of muscle oxidation were determined by immunohistochemistry. Data were presented as medians. The intervention induced 7% weight loss (P = 0.001) and increased vigorous PA by 24 min/wk (P = 0.02). During exercise, energy expenditure decreased, efficiency increased (P ≤ 0.03), and fatty acid oxidation (FAO) did not change. Succinate dehydrogenase increased (P = 0.001), but fiber type remained the same. Post-intervention subjects' resting metabolism remained similar to controls. Efficiency was lower in post-intervention subjects compared with normal-weight controls exercising at 25 W (P ≤ 0.002) and compared with all controls exercising at 60% VO2peak (P ≤ 0.019). Resting and exercise FAO of post-intervention subjects remained similar to adults with less severe obesity. Succinate dehydrogenase and fiber type were similar across all body weight statuses. While metabolic adaptations to PA during weight loss occur in adults with severe obesity, FAO does not change. Resulting FAO during rest and exercise remains similar to adults with less severe obesity. © 2016 The Obesity Society.

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.

[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.

Cardiovascular Risk Stratification in Patients with Metabolic Syndrome Without Diabetes or Cardiovascular Disease: Usefulness of Metabolic Syndrome Severity Score.

PubMed

Masson, Walter; Epstein, Teo; Huerín, Melina; Lobo, Lorenzo Martín; Molinero, Graciela; Angel, Adriana; Masson, Gerardo; Millán, Diana; De Francesca, Salvador; Vitagliano, Laura; Cafferata, Alberto; Losada, Pablo

2017-09-01

The estimated cardiovascular risk determined by the different risk scores, could be heterogeneous in patients with metabolic syndrome without diabetes or vascular disease. This risk stratification could be improved by detecting subclinical carotid atheromatosis. To estimate the cardiovascular risk measured by different scores in patients with metabolic syndrome and analyze its association with the presence of carotid plaque. Non-diabetic patients with metabolic syndrome (Adult Treatment Panel III definition) without cardiovascular disease were enrolled. The Framingham score, the Reynolds score, the new score proposed by the 2013 ACC/AHA Guidelines and the Metabolic Syndrome Severity Calculator were calculated. Prevalence of carotid plaque was determined by ultrasound examination. A Receiver Operating Characteristic analysis was performed. A total of 238 patients were enrolled. Most patients were stratified as "low risk" by Framingham score (64%) and Reynolds score (70.1%). Using the 2013 ACC/AHA score, 45.3% of the population had a risk ≥7.5%. A significant correlation was found between classic scores but the agreement (concordance) was moderate. The correlation between classical scores and the Metabolic Syndrome Severity Calculator was poor. Overall, the prevalence of carotid plaque was 28.2%. The continuous metabolic syndrome score used in our study showed a good predictive power to detect carotid plaque (area under the curve 0.752). In this population, the calculated cardiovascular risk was heterogenic. The prevalence of carotid plaque was high. The Metabolic Syndrome Severity Calculator showed a good predictive power to detect carotid plaque.

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.

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.

Accelerated acidosis in response to variable fetal heart rate decelerations in chronically hypoxic ovine fetuses.

PubMed

Amaya, Kevin E; Matushewski, Brad; Durosier, L Daniel; Frasch, Martin G; Richardson, Bryan S; Ross, Michael G

2016-02-01

Due to limitations of technology, clinicians are typically unable to determine if human fetuses are normoxic or moderately, chronically hypoxic. Risk factors for chronic hypoxia include fetal growth restriction, which is associated with an increased incidence of oligohydramnios and thus a risk for umbilical cord occlusion (UCO) and variable fetal heart rate (FHR) decelerations. At delivery, fetal growth restriction infants (<3rd percentile) have nearly twice the incidence of low Apgar scores and umbilical pH <7.0. Despite the risks of oligohydramnios and intermittent UCO, there is little understanding of the acid/base responses rates of chronically hypoxic fetuses to variable FHR decelerations as might occur during human labor. We sought to compare the increase in base deficit (BD) among chronically hypoxic as compared to normoxic ovine fetuses in response to simulated mild, moderate, and severe variable FHR decelerations. Near-term ovine fetuses were chronically prepared with brachial artery catheters and an inflatable umbilical cuff occluder. Following a recovery period, normoxic (n = 9) and spontaneously hypoxic (n = 5) fetuses were identified (arterial O2 saturation ≤55%). Both animal groups underwent graded, 1-minute occlusions every 2.5 minutes with 1 hour of mild (∼30 beats/min [bpm] decrease from baseline), 1 hour of moderate (∼60 bpm decrease from baseline), and up to 2 hours of severe (∼90 bpm decrease from baseline) variable FHR decelerations until fetal arterial pH reached 7.00, when occlusions were stopped. Repetitive UCO resulted in development of acidosis (pH <7.0) in both groups. Hypoxic and normoxic fetuses demonstrated similar BD increases in response to both mild (0.39, interquartile range [IQR] 0.28-0.45 vs 0.26, IQR 0.01-0.30 mEq/L/10 min, P = .25) and severe (1.97, IQR 1.50-2.43 vs 1.51, IQR 0.97-2.45 mEq/L/10 min, P = .63) variable decelerations. However, moderate variable decelerations increased BD in hypoxic fetuses at 2.5 times the

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.

[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.

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.

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

Severe cyanide poisoning from an alternative medicine treatment with amygdalin and apricot kernels in a 4-year-old child.

PubMed

Sauer, Harald; Wollny, Caroline; Oster, Isabel; Tutdibi, Erol; Gortner, Ludwig; Gottschling, Sven; Meyer, Sascha

2015-05-01

The use of complementary and alternative medicine (CAM) is widespread in children with cancer and is poorly regulated. Case report. We describe a case of severe cyanide poisoning arising from CAM use. A severely agitated, encephalopathic, unresponsive 4-year-old boy (initial Glasgow Coma Scale of 3) with a history of metastatic ependymoma was brought to our emergency department by ambulance services. Initial blood gas analysis demonstrated severe metabolic/lactic acidosis. On detailed questioning of the parents, the use of CAM including intravenous and oral "vitamin B 17" (amygdalin) and oral apricot kernel was reported. After administering sodium thiosulfate, rapid improvement in his medical condition with complete recovery without need for further intensive care treatment was seen. Serum cyanide level was markedly elevated. Cyanide poisoning can be the cause of severe encephalopathy in children receiving CAM treatment with substances containing cyanogenic glycosides.

Thiamine Deficiency in Tropical Pediatrics: New Insights into a Neglected but Vital Metabolic Challenge

PubMed Central

Hiffler, Laurent; Rakotoambinina, Benjamin; Lafferty, Nadia; Martinez Garcia, Daniel

2016-01-01

In humans, thiamine is a micronutrient prone to depletion that may result in severe clinical abnormalities. This narrative review summarizes current knowledge on thiamine deficiency (TD) and bridges the gap between pathophysiology and clinical presentation by integrating thiamine metabolism at subcellular level with its function to vital organs. The broad clinical spectrum of TD is outlined, with emphasis on conditions encountered in tropical pediatric practice. In particular, TD is associated with type B lactic acidosis and classic forms of beriberi in children, but it is often unrecognized. Other severe acute conditions are associated with hypermetabolism, inducing a functional TD. The crucial role of thiamine in infant cognitive development is also highlighted in this review, along with analysis of the potential impact of TD in refeeding syndrome during severe acute malnutrition (SAM). This review aims to increase clinical awareness of TD in tropical settings where access to diagnostic tests is poor, and advocates for an early therapeutic thiamine challenge in resource-limited settings. Moreover, it provides evidence for thiamine as treatment in critical conditions requiring metabolic resuscitation, and gives rationale to the consideration of increased thiamine supplementation in therapeutic foods for malnourished children. PMID:27379239

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)

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.

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

Obesity Severity and Duration Are Associated With Incident Metabolic Syndrome: Evidence Against Metabolically Healthy Obesity From the Multi-Ethnic Study of Atherosclerosis

PubMed Central

Foster, Meredith C.; Kalyani, Rita R.; Vaidya, Dhananjay; Burke, Gregory L.; Woodward, Mark; Anderson, Cheryl A.M.

2016-01-01

Context: Although the health risks of obesity compared to normal weight have been well studied, the cumulative risk associated with chronic obesity remains unknown. Specifically, debate continues about the importance of recommending weight loss for those with metabolically healthy obesity. Objective: We hypothesized that relatively greater severity and longer duration of obesity are associated with greater incident metabolic syndrome. Design, Setting, Participants, and Measures: Using repeated measures logistic regression with random effects, we investigated the association of time-varying obesity severity and duration with incident metabolic syndrome in 2,748 Multi-Ethnic Study of Atherosclerosis participants with obesity (body mass index ≥30 kg/m2) at any visit. Obesity duration was defined as the cumulative number of visits with measured obesity and obesity severity by the World Health Organization levels I–III based on body mass index. Metabolic syndrome was defined using Adult Treatment Panel III criteria modified to exclude waist circumference. Results: Higher obesity severity (level II odds ratio [OR], 1.32 [95% confidence interval, 1.09–1.60]; level III OR, 1.63 [1.25–2.14] vs level I) and duration (by number of visits: two visits OR, 4.43 [3.54–5.53]; three visits OR, 5.29 [4.21–6.63]; four visits OR, 5.73 [4.52–7.27]; five visits OR, 6.15 [4.19–9.03] vs one visit duration of obesity) were both associated with a higher odds of incident metabolic syndrome. Conclusion: Both duration and severity of obesity are positively associated with incident metabolic syndrome, suggesting that metabolically healthy obesity is a transient state in the pathway to cardiometabolic disease. Weight loss should be recommended to all individuals with obesity, including those who are currently defined as metabolically healthy. PMID:27552544

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

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

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.

Severe metabolic alkalosis due to pyloric obstruction: case presentation, evaluation, and management.

PubMed

McCauley, Meredith; Gunawardane, Manjula; Cowan, Mark J

2006-12-01

A 46-year-old man presented to the emergency room with severe metabolic alkalosis, hypokalemia, and respiratory failure requiring intubation and mechanical ventilation. The cause of his acid-base disorder was initially unclear. Although alkalosis is common in the intensive care unit, metabolic alkalosis of this severity is unusual, carries a very high mortality rate, and requires careful attention to the pathophysiology and differential diagnosis to effectively evaluate and treat the patient. A central concept in the diagnosis of metabolic alkalosis is distinguishing chloride responsive and chloride nonresponsive states. Further studies are then guided by the history and physical examination in most cases. By using a systematic approach to the differential diagnosis, we were able to determine that a high-grade gastric outlet obstruction was the cause of the patients' alkalosis and to offer effective therapy for his condition. A literature review and algorithm for the diagnosis and management of metabolic alkalosis are also presented.

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

Metabolic Surgery Profoundly Influences Gut Microbial-Host Metabolic Crosstalk

PubMed Central

Li, Jia V.; Ashrafian, Hutan; Bueter, Marco; Kinross, James; Sands, Caroline; le Roux, Carel W; Bloom, Stephen R.; Darzi, Ara; Athanasiou, Thanos; Marchesi, Julian R.; Nicholson, Jeremy K.; Holmes, Elaine

2013-01-01

Background and Aims Bariatric surgery is increasingly performed worldwide to treat morbid obesity and is also known as metabolic surgery to reflect its beneficial metabolic effects especially with respect to improvement in type 2 diabetes. Understanding surgical weight loss mechanisms and metabolic modulation is required to enhance patient benefits and operative outcomes. Methods We apply a parallel and statistically integrated metagenomic and metabonomic approach to characterize Roux-en-Y gastric bypass (RYGB) effects in a rat model. Results We show substantial shifts of the main gut phyla towards higher levels of Proteobacteria (52-fold) specifically Enterobacter hormaechei. We also find low levels of Firmicutes (4.5-fold) and Bacteroidetes (2-fold) in comparison to sham-operated rats. Faecal extraction studies reveal a decrease in faecal bile acids and a shift from protein degradation to putrefaction through decreased faecal tyrosine with concomitant increases in faecal putrescine and diamnoethane. We find decreased urinary amines and cresols and demonstrate indices of modulated energy metabolism post-RYGB including decreased urinary succinate, 2-oxoglutarate, citrate and fumarate. These changes could also indicate renal tubular acidosis, which associates with increased flux of mitochondrial tricarboxylic acid cycle intermediates. A surgically-induced effect on the gut-brain-liver metabolic axis is inferred by increased neurotropic compounds; faecal γ-aminobutyric acid (GABA) and glutamate. Conclusion This profound co-dependence of mammalian and microbial metabolism, which is systematically altered following RYGB surgery, suggests that RYGB exerts local and global metabolic activities. The effect of RYGB surgery on the host metabolic-microbial crosstalk augments our understanding of the metabolic phenotype of bariatric procedures and can facilitate enhanced treatments for obesity-related diseases. PMID:21572120

Metabolic syndrome in patients with severe mental illness in Gorgan

PubMed Central

Kamkar, Mohammad Zaman; Sanagoo, Akram; Zargarani, Fatemeh; Jouybari, Leila; Marjani, Abdoljalal

2016-01-01

Background: Metabolic syndrome is commonly associated with cardiovascular diseases and psychiatric mental illness. Hence, we aimed to assess the metabolic syndrome among severe mental illness (SMI). Materials and Methods: The study included 267 patients who were referred to the psychiatric unit at 5th Azar Education Hospital of Golestan University of Medical Sciences in Gorgan, Iran. Results: The mean waist circumference, systolic and diastolic blood pressure, triglyceride and fasting blood glucose levels were significantly higher in the SMI with metabolic syndrome, but the high density lipoprotein (HDL)-cholesterol was significantly lower. The prevalence of metabolic syndrome in SMI patients was 20.60%. There were significant differences in the mean of waist circumference, systolic (except for women) and diastolic blood pressure, triglyceride, HDL-cholesterol and fasting blood glucose in men and women with metabolic syndrome when compared with subjects without metabolic syndrome. The prevalence of metabolic syndrome in SMI women was higher than men. The most age distribution was in range of 30-39 years old. The most prevalence of metabolic syndrome was in age groups 50-59 years old. The prevalence of metabolic syndrome was increased from 30 to 59 years old. Conclusion: The prevalence of metabolic syndrome in patients with SMI in Gorgan is almost similar to those observed in Asian countries. The prevalence of metabolic syndrome was lower than western countries. These observations may be due to cultural differences in the region. It should be mention that the families of mental illness subjects in our country believe that their patients must be cared better than people without mental illness. These findings of this study suggest that mental illness patients are at risk of metabolic syndrome. According to our results, risk factors such as age and gender differences may play an important role in the presence of metabolic syndrome. In our country, women do less

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

[Neonatal eucapnic pH at birth: Application in a cohort of 5392 neonates].

PubMed

Racinet, C; Peresse, J-F; Richalet, G; Corne, C; Ouellet, P

2016-09-01

To apply a newly concept of neonatal eucapnic pH at birth [pH euc (n)] and compare its contribution towards conventional criteria of severe metabolic acidosis. Analysis of a cohort of 5392 neonates from 2010 to 2014 in a level 1 maternity. clinical data (birth weight, gestational age, mode of delivery, APGAR score) were collected from archived files. Biological data were collected from umbilical cord blood, consisting of pH, PCO2, Base deficit, lactate. Eucapnic pH and eucapnic base deficit were calculated from pH and PCO2 with the Henderson-Hasselbalch equation applied in the Charles-Racinet diagram and/or with an Excel spreadsheet. Data set the prevalence of neonatal acidemia<7.00 to 0.62 %. The current cohort shows 32 cases of severe neonatal metabolic acidosis according to ACOG-AAP (2014) criteria and 26/29 cases according to McLennan (2015) criteria, of which 80 % were born by cesarean section or instrumental delivery. In 55 % of cases, calculated eucapnic pH at birth did not confirm the severity of metabolic acidosis based on a threshold set at 7.11. Five cases were transferred in neonatalogy only on clinical considerations of poor neonatal adaptation but not on biological consideration (pH euc<7.11 was equally distributed between transferred and non-transferred neonates, P=0.76; the same distribution was observed with the pH, P=0.20) and followed normal outcome. The pH determination provides information only on the degree of acidemia and not on respiratory and/or metabolic components. Moreover, hypercapnia always present at birth is not included in the instructions to determine a metabolic acidosis (The American College of Obstetricians and Gynecologists, 2014; MacLennan et al., 2015). The new concept of neonatal eucapnic pH at birth accounts for only the metabolic component. We feel it should fine tune indications for cerebral hypothermia and thus improve its effectiveness. From a medicolegal perspective, for cases of cerebral palsy, it often

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

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…

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

Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment

PubMed Central

Justus, Calvin R.; Sanderlin, Edward J.; Yang, Li V.

2015-01-01

Cancer cells preferentially utilize glycolysis, instead of oxidative phosphorylation, for metabolism even in the presence of oxygen. This phenomenon of aerobic glycolysis, referred to as the “Warburg effect”, commonly exists in a variety of tumors. Recent studies further demonstrate that both genetic factors such as oncogenes and tumor suppressors and microenvironmental factors such as spatial hypoxia and acidosis can regulate the glycolytic metabolism of cancer cells. Reciprocally, altered cancer cell metabolism can modulate the tumor microenvironment which plays important roles in cancer cell somatic evolution, metastasis, and therapeutic response. In this article, we review the progression of current understandings on the molecular interaction between cancer cell metabolism and the tumor microenvironment. In addition, we discuss the implications of these interactions in cancer therapy and chemoprevention. PMID:25988385

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

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.

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.
.

Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis.

PubMed

Lin, Yan-Ren; Li, Chao-Jui; Syu, Shih-Han; Wen, Cheng-Hao; Buddhakosai, Waradee; Wu, Han-Ping; Hsu Chen, Cheng; Lu, Huai-En; Chen, Wen-Liang

2016-01-01

Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n = 20) and control (normal saline, n = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group ( p < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level.

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.

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.

Low-flow venovenous CO₂ removal in association with lung protective ventilation strategy in patients who develop severe progressive respiratory acidosis after lung transplantation.

PubMed

Ruberto, F; Bergantino, B; Testa, M C; D'Arena, C; Zullino, V; Congi, P; Paglialunga, S G; Diso, D; Venuta, F; Pugliese, F

2013-09-01

Primary graft dysfunction (PGD) might occur after lung transplantation. In some severe cases, conventional therapies like ventilatory support, administration of inhaled nitric oxide (iNO), and intravenous prostacyclins are not sufficient to provide an adequate gas exchange. The aim of our study was to evaluate the use of a lung protective ventilation strategy associated with a low-flow venovenous CO2 removal treatment to reduce ventilator-associated injury in patients that develop severe PGD after lung transplantation. From January 2009 to January 2011, 3 patients developed PGD within 24 hours after lung transplantation. In addition to conventional medical treatment, including hemodynamic support, iNO and prostaglandin E1 (PGE1), we initiated a ventilatory protective strategy associated with low-flow venovenous CO2 removal treatment (LFVVECCO2R). Hemodynamic and respiratory parameters were assessed at baseline as well as after 3, 12, 24, and 48 hours. No adverse events were registered. Despite decreased baseline elevated pulmonary positive pressures, application of a protective ventilation strategy with LFVVECCO2R reduced PaCO2 and pulmonary infiltrates as well as increased pH values and PaO2/FiO2 ratios. Every patient showed simultaneous improvement of clinical and hemodynamic conditions. They were weaned from mechanical ventilation and extubated after 24 hours after the use of the low-flow venovenous CO2 removal device. The use of LFVVECCO2R together with a protective lung ventilation strategy during the perioperative period of lung transplantation may be a valid clinical strategy for patients with PGD and severe respiratory acidosis occured despite adequate mechanical ventilation. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

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

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.

Seasonal influence over serum and urine metabolic markers in submariners during prolonged patrols

PubMed Central

Holy, Xavier; Bégot, Laurent; Renault, Sylvie; Butigieg, Xavier; André, Catherine; Bonneau, Dominique; Savourey, Gustave; Collombet, Jean-Marc

2015-01-01

Within the framework of earlier publications, we have consistently dedicated our investigations to eliciting the effects of both seasonal vitamin D deficiency and submarine-induced hypercapnia on serum parameters for acid–base balance and bone metabolism in submariners over a 2-month winter (WP) or summer (SP) patrols. The latest findings reported herein, contribute further evidence with regard to overall physiological regulations in the same submariner populations that underwent past scrutiny. Hence, urine and blood samples were collected in WP and SP submariners at control prepatrol time as well as on submarine patrol days 20, 41, and 58. Several urine and serum metabolic markers were quantified, namely, deoxypyridinoline (DPD), lactate, albumin, creatinine, nonesterified fatty acids (NEFA), and ionized sodium (Na+) or potassium (K+), with a view to assessing bone, muscle, liver, or kidney metabolisms. We evidenced bone metabolism alteration (urine DPD, calcium, and phosphorus) previously recorded in submarine crewmembers under prolonged patrols. We also highlighted transitory modifications in liver metabolism (serum albumin) occurring within the first 20 days of submersion. We further evidenced changes in submariners’ renal physiology (serum creatinine) throughout the entire patrol time span. Measurements of ionic homeostasis (serum Na+ and K+) displayed potential seasonal impact over active ionic pumps in submariners. Finally, there is some evidence that submersion provides beneficial conditions prone to fend off seasonal lactic acidosis (serum lactate) detected in WP submariners. PMID:26265754

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.

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.

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: ...

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.

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.

Fanconi syndrome and severe polyuria: an uncommon clinicobiological presentation of a Gitelman syndrome.

PubMed

Bouchireb, Karim; Boyer, Olivia; Mansour-Hendili, Lamisse; Garnier, Arnaud; Heidet, Laurence; Niaudet, Patrick; Salomon, Remi; Poussou, Rosa Vargas

2014-08-11

Gitelman syndrome is an autosomal recessive tubulopathy characterized by hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria. The majority of patients do not present with symptoms until late childhood or adulthood, and the symptoms are generally mild. We report here the first case of Gitelman syndrome presenting with the biological features of Fanconi syndrome and an early polyuria since the neonatal period. We discuss in this article the atypical electrolytes losses found in our patient, as well as the possible mechanisms of severe polyuria. A 6-year-old Caucasian girl was admitted via the Emergency department for vomiting, and initial laboratory investigations found hyponatremia, hypokalemia, metabolic acidosis with normal anion gap, hypophosphatemia, and hypouricemia. Urinalysis revealed Na, K, Ph and uric acid losses. Thus, the initial biological profile was in favor of a proximal tubular defect. However, etiological investigations were inconclusive and the patient was discharged with potassium chloride and phosphorus supplementation. Three weeks later, further laboratory analysis indicated persistent hypokalemia, a metabolic alkalosis, hypomagnesemia, and hypocalciuria. We therefore sequenced the SLC12A3 gene and found a compound heterozygosity for 2 known missense mutations. Gitelman syndrome can have varying and sometimes atypical presentations, and should be suspected in case of hypokalemic tubular disorders that do not belong to any obvious syndromic entity. In this case, the proximal tubular dysfunction could be secondary to the severe hypokalemia. This report emphasizes the need for clinicians to repeat laboratory tests in undiagnosed tubular disorders, especially not during decompensation episodes.

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

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.

Risk factors of shock in severe falciparum malaria.

PubMed

Arnold, Brendan J; Tangpukdee, Noppadon; Krudsood, Srivicha; Wilairatana, Polrat

2013-07-04

The objective of this study was to determine the risk factors for the development of shock in adult patients admitted with severe falciparum malaria. As an unmatched case-control study, the records of patients who were admitted to the Bangkok Hospital for Tropical Diseases, Thailand, between the years 2000-2010, were reviewed. One hundred patients with severe falciparum malaria and shock, and another 100 patients with severe malaria but without shock were studied. Demographics, presenting symptoms, physical observations, and laboratory data of these patients were analyzed. Five risk factors for the development of shock were identified: female gender (OR 6.16; 95% CI 3.17-11.97), red cell distribution width (RDW) >15% (adjusted OR 2.90; 95% CI 1.11-7.57), anorexia (adjusted OR 2.76; 95% CI 1.03-7.39), hypoalbuminemia (adjusted OR 2.19; 95% CI 1.10-4.34), and BUN-creatinine ratio >20 (adjusted OR 2.38; 95% CI 1.22-4.64). Diarrhea was found to be a protective factor (adjusted OR 0.33; 95% CI 0.14-0.78). Metabolic acidosis was only weakly correlated to mean arterial blood pressure on admission (r(s) = 0.23). Female gender was the strongest risk factor for the development of shock. We concluded that female gender, RDW >15%, anorexia, hypoalbuminemia, and BUN-creatinine ratio >20 were risk factors of shock development in severe falciparum malaria.

MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis