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PubMed1989

Nephrolithiasis in renal tubular acidosis.

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. It may be due to metabolic acidosis, usually in children with a hereditary defect in urine acidification. In other cases familial idiopathic hypercalciuria causes nephrocalcinosis and nephrolithiasis resulting in distal tubular damage and type I renal tubular acidosis. In these latter cases hypercalciuria is present in complete and incomplete type I renal tubular acidosis. Potassium citrate appears to reduce calcium excretion in both types of hypercalciuric type I renal tubular acidosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Acidosis, Renal Tubular↗
PubMed1999

Serum anion gap in the differential diagnosis of metabolic acidosis in critically ill newborns.

OBJECTIVES: To determine in critically ill newborn infants (1) the range of the serum anion gap without metabolic acidosis and (2) whether the serum anion gap can be used to distinguish newborns with lactic acidosis from those with hyperchloremic metabolic acidosis. STUDY DESIGN: Umbilical arterial blood gases and serum electrolyte and lactate concentrations were measured simultaneously in 210 samples from 63 infants over the first week of life. Metabolic acidosis was defined as a blood base deficit (BD) >4 mmol/L. The anion gap was calculated as [Na(+)] - [C1(-)] - [TCO (2)]. Lactic acidosis was defined as a serum lactate concentration >2 SD above the mean serum lactate concentration in samples without metabolic acidosis. RESULTS: In 89 blood samples with BD <4 mmol/L, serum lactate concentration decreased with postnatal age (r = 0.51). The upper limit of serum lactate concentration was 3.8 mmol/L at less than 48 hours, 2.4 mmol/L between 48 and 96 hours, and 1.5 mmol/L for infants greater than 96 hours of age. The mean serum anion gap +/- 2 SD in 174 samples without lactic acidosis was 8 +/- 4 mmol/L; in 36 samples with lactic acidosis it was 16 +/- 9 mmol/L (P <.0001). Serum anion gap and lactate concentration were poorly correlated for samples without lactic acidosis (r = 0.04) but highly correlated in those with lactic acidosis (r = 0.81, P <.0001). None of the 85 samples with metabolic acidosis but without lactic acidosis had an anion gap >16 mmol/L; only 4 of 36 samples with lactic acidosis had an anion gap <8 meq/L. However, 25 of 36 samples with lactic acidosis had serum anion gaps of 8 to 16 mmol/L. CONCLUSION: In the presence of metabolic acidosis, a serum anion gap >16 mmol/L is highly predictive of lactic acidosis; a serum anion gap <8 is highly predictive of the absence of lactic acidosis; an anion gap = 8 - 16 mmol/L has no use in the differential diagnosis of metabolic acidosis in the critically ill newborn.

Acid-Base Equilibrium↗
PubMed2003

Metabolic acidosis in maintenance dialysis patients: clinical considerations.

Metabolic acidosis in maintenance dialysis patients: Clinical considerations. Metabolic acidosis is a common consequence of advanced chronic renal failure (CRF) and maintenance dialysis (MD) therapies are not infrequently unable to completely correct the base deficit. In MD patients, severe metabolic acidosis is associated with an increased relative risk for death. The chronic metabolic acidosis of the severity commonly encountered in patients with advanced CRF has two well-recognized major systemic consequences. First, metabolic acidosis induces net negative nitrogen and total body protein balance, which improves upon bicarbonate supplementation. The data suggest that metabolic acidosis is both catabolic and antianabolic. Emerging data also indicate that metabolic acidosis may be one of the triggers for chronic inflammation, which may in turn promote protein catabolism among MD patients. In contrast to these findings, metabolic acidosis may be associated with a decrease in hyperleptinemia associated with CRF. Several studies have shown that correction of metabolic acidosis among MD patients is associated with modest improvements in the nutritional status. Second, metabolic acidosis has several effects on bone, causing physicochemical dissolution of bone and cell-mediated bone resorption (inhibition of osteoblast and stimulation of osteoclast function). Metabolic acidosis is probably also associated with worsening of secondary hyperparathyroidism. Data on the effect of correction of metabolic acidosis on renal osteodystrophy, however, are limited. Preliminary evidence suggest that metabolic acidosis may play a role in beta2-microglobulin accumulation, as well as the hypertriglyceridemia seen in renal failure. Given the body of evidence pointing to the several systemic consequences of metabolic acidosis, a more aggressive approach to the correction of metabolic acidosis is proposed.

Acidosis↗
PubMed1999

In vitro metabolic and respiratory acidosis selectively inhibit osteoblastic matrix gene expression.

Clinically, a decrease in blood pH may be due to either a reduction in bicarbonate concentration ([HCO(-)(3)], metabolic acidosis) or an increase in PCO(2) (respiratory acidosis). In mammals, metabolic acidosis induces a far greater increase in urine calcium excretion than respiratory acidosis. In cultured bone, metabolic acidosis induces a marked increase in calcium efflux and a decrease in osteoblastic collagen synthesis, whereas isohydric respiratory acidosis has little effect on either parameter. We have shown that metabolic acidosis prevents the normal developmental increase in the expression of RNA for matrix Gla protein and osteopontin in chronic cultures of primary murine calvarial bone cells (predominantly osteoblasts) but does not alter expression of osteonectin. To compare the effects of isohydric metabolic and respiratory acidosis on expression of these genes, bone cell cultures were incubated in medium at pH approximately 7.2 to model metabolic ([HCO(-)(3)], approximately 13 mM) or respiratory (PCO(2), approximately 80 mmHg) acidosis or at pH approximately 7.4 as a control. Cells were sampled at weeks 4, 5, and 6 to assess specific RNA content. At all time periods studied, both metabolic and respiratory acidosis inhibited the expression of RNA for matrix Gla protein and osteopontin to a similar extent, whereas there was no change in osteonectin expression. In contrast to the significant difference in the effects of metabolic and respiratory acidosis on bone calcium efflux and osteoblastic collagen synthesis, these two forms of acidosis have a similar effect on osteoblastic RNA expression of both matrix Gla protein and osteopontin. Thus, although several aspects of bone cell function are dependent on the type of acidosis, expression of these two matrix genes appears to be regulated by extracellular pH, independently of the type of acidosis.

Acidosis↗
PubMed2005

Circulating anions usually associated with the Krebs cycle in patients with metabolic acidosis.

INTRODUCTION: Acute metabolic acidosis of non-renal origin is usually a result of either lactic or ketoacidosis, both of which are associated with a high anion gap. There is increasing recognition, however, of a group of acidotic patients who have a large anion gap that is not explained by either keto- or lactic acidosis nor, in most cases, is inappropriate fluid resuscitation or ingestion of exogenous agents the cause. METHODS: Plasma ultrafiltrate from patients with diabetic ketoacidosis, lactic acidosis, acidosis of unknown cause, normal anion gap metabolic acidosis, or acidosis as a result of base loss were examined enzymatically for the presence of low molecular weight anions including citrate, isocitrate, alpha-ketoglutarate, succinate, malate and d-lactate. The results obtained from the study groups were compared with those obtained from control plasma from normal volunteers. RESULTS: In five patients with lactic acidosis, a significant increase in isocitrate (0.71 +/- 0.35 mEq l-1), alpha-ketoglutarate (0.55 +/- 0.35 mEq l-1), malate (0.59 +/- 0.27 mEq l-1), and d-lactate (0.40 +/- 0.51 mEq l-1) was observed. In 13 patients with diabetic ketoacidosis, significant increases in isocitrate (0.42 +/- 0.35 mEq l-1), alpha-ketoglutarate (0.41 +/- 0.16 mEq l-1), malate (0.23 +/- 0.18 mEq l-1) and d-lactate (0.16 +/- 0.07 mEq l-1) were seen. Neither citrate nor succinate levels were increased. Similar findings were also observed in a further five patients with high anion gap acidosis of unknown origin with increases in isocitrate (0.95 +/- 0.88 mEq l-1), alpha-ketoglutarate (0.65 +/- 0.20 mEq l-1), succinate (0.34 +/- 0.13 mEq l-1), malate (0.49 +/- 0.19 mEq l-1) and d-lactate (0.18 +/- 0.14 mEq l-1) being observed but not in citrate concentration. In five patients with a normal anion gap acidosis, no increases were observed except a modest rise in d-lactate (0.17 +/- 0.14 mEq l-1). CONCLUSION: The levels of certain low molecular weight anions usually associated with intermediary metabolism were found to be significantly elevated in the plasma ultrafiltrate obtained from patients with metabolic acidosis. Our results suggest that these hitherto unmeasured anions may significantly contribute to the generation of the anion gap in patients with lactic acidosis and acidosis of unknown aetiology and may be underestimated in diabetic ketoacidosis. These anions are not significantly elevated in patients with normal anion gap acidosis.

Acid-Base Equilibrium↗
PubMed1988

Net proton influx into bone during metabolic, but not respiratory, acidosis.

During acute metabolic acidosis there is a net influx of protons into bone, decreasing the elevated proton concentration. Whether there is an influx of protons into bone during acute respiratory acidosis is not known. To determine the effect of respiratory acidosis on net proton flux (JH) relative to bone, we compared JH from neonatal mouse calvariae incubated for 3 h in medium acidified by an increase in PCO2 (respiratory acidosis) with that from calvariae incubated in medium acidified to the same extent by a decrease in bicarbonate concentration (metabolic acidosis). The initial medium pH with respiratory acidosis was not different from that with metabolic acidosis (7.108 +/- 0.005 vs. 7.091 +/- 0.007, respectively, P = NS). During respiratory acidosis there was no JH from bone relative to the medium (JH = 236 +/- 93 neq.bone-1.3h-1, P = NS vs. 0); however, during metabolic acidosis there was net proton influx from the medium into bone (JH = -703 +/- 108, P less than 0.05 vs. 0, P less than 0.001 vs. respiratory acidosis). There was less calcium efflux from bone during respiratory than during metabolic acidosis (JCa = 68 +/- 6 nmol.bone-1.3 h-1 vs. 100 +/- 9, respectively, P less than 0.001). There is a net influx of protons into bone in vitro during acute metabolic, but not during acute respiratory, acidosis. The smaller calcium efflux during respiratory acidosis may indicate less net bone mineral dissolution and thus less buffer release into the medium.

Acidosis↗
PubMed1992

[Metabolic acidosis in severe acute asthma. Effect of alkaline therapy].

Respiratory acidosis of severe acute asthma is a severity factor. In this paper the treatment of associated metabolic acidosis is discussed. Among 34 consecutive episodes of severe acute asthma with acidosis (pH < 7.35) treated with continuous adrenaline perfusion, theophylline and hydrocortisone hemisuccinate, respiratory acidosis was observed in 12, metabolic acidosis in 2 and mixed respiratory and metabolic acidosis in 20. The association of hypercapnic acidosis with hypochloraemic acidosis reflected a time of installation longer than when respiratory acidosis only was present (p < 0.05). Among the 22 patients who had metabolic acidosis on admission, 14 were treated with 168 +/- 82 mmol of sodium bicarbonate, the remaining 8 patients being untreated and acting as controls. The rapidity with which pH was corrected was the same in the treated and untreated groups (9.1 +/- 5.5 hours vs 6.7 +/- 3.7 hours), whereas dyspnoea (respiratory rate < 18/min) was more rapidly corrected in the treated group that in controls (11.6 +/- 5.7 hours vs 5.9 +/- 5.9 hours; p < 0.05). It is concluded that in more than 50% of the cases respiratory acidosis of severe acute asthma is associated with a metabolic acidosis. Correcting this metabolic acidosis with sodium bicarbonate results in improvement of respiration, perhaps by facilitating the action of bronchodilator catecholamines.

Acidosis↗
PubMed1987

Influence of intracellular acidosis on contractile function in the working rat heart.

The decrease in myocardial contractility during ischemia, hypoxia, and extracellular acidosis has been attributed to intracellular acidosis. Previous studies of the relationship between pH and contractile state have utilized respiratory or metabolic acidosis to alter intracellular pH. We developed a model in the working perfused rat heart to study the effects of intracellular acidosis with normal external pH and optimal O2 delivery. Intracellular pH and high-energy phosphates were monitored by 31P nuclear magnetic resonance spectroscopy. Hearts were perfused to a steady state with a medium containing 10 mM NH4Cl (extracellular pH, 7.4). The subsequent washout of NH3 from the cytosol generated a slight acidosis (from intracellular pH 7.0 to 6.8) which was associated with little change in the determinants of O2 consumption (rate-pressure product) and O2 delivery (coronary flow). Acidosis induced a substantial decrease in aortic flow and stroke volume which was associated with little change in peak systolic pressure. Results were qualitatively similar at different external [Ca2+] (1.75, 2.5, 3.15 mM) and preload (12 or 21 cmH2O) but were most prominent at the lowest external [Ca2+] and left atrial pressure. In contrast to this model of isolated intracellular acidosis, hearts subject to a respiratory (extracellular plus intracellular) acidosis showed a marked reduction in pressure development. It was concluded that 1) for the same intracellular acidosis the influence on tension development was more pronounced with a combined extra- and intracellular acidosis than with an isolated intracellular acidosis, and 2) stroke volume at constant preload was impaired by intracellular acidosis even though changes in developed pressure were minimal. These observations suggest that isolated intracellular acidosis has adverse effects on diastolic compliance and/or relaxation.

Acid-Base Equilibrium↗
PubMed1994

Systemic acidosis after controlled hypotension activates catechol activity in the vasomotor center.

Activation of the catechol metabolism, assessed with in vivo voltammetry, in the vasopressor area of the vasomotor center was investigated during systemic acidosis occurring after controlled hypotension. Rats anesthetized with halothane were mechanically ventilated. Sodium nitroprusside lowered mean arterial pressure to 55 mmHg for > or = 20 min. Arterial blood gases allowed us to group rats according to whether they showed symptoms of metabolic acidosis (pH < or = 7.34) immediately after controlled hypotension. To assess the effect of systemic acidosis independently of the progressive decline in pressure observed during the recovery period after controlled hypotension, we used phenylephrine infusion to maintain mean arterial pressure at baseline pressure during the recovery period after controlled hypotension in two groups of animals. Systemic acidosis increased the catechol signal in a prolonged manner [nitroprusside with acidosis (n = 7) vs. nitroprusside without acidosis (n = 5); P < 0.0001]. This catechol activation was greater when pressure was restored after hypotension [nitroprusside with acidosis plus phenylephrine (n = 5) vs. nitroprusside with acidosis over the whole interval (from -30 to +150 min); P < 0.05]. When the nitroprusside with acidosis group and nitroprusside with acidosis plus phenylephrine group were compared, hypercapnia had an involvement in the larger increase of the catechol signal observed in the nitroprusside with acidosis plus phenylephrine group [arterial PCO2: nitroprusside with acidosis vs. nitroprusside with acidosis plus phenylephrine over the whole interval (from -30 to +150 min) and at +30 and +60 min; all P < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed2006

Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients.

INTRODUCTION: Acid-base abnormalities are common in the intensive care unit (ICU). Differences in outcome exist between respiratory and metabolic acidosis in similar pH ranges. Some forms of metabolic acidosis (for example, lactate) seem to have worse outcomes than others (for example, chloride). The relative incidence of each type of disorder is unknown. We therefore designed this study to determine the nature and clinical significance of metabolic acidosis in critically ill patients. METHODS: An observational, cohort study of critically ill patients was performed in a tertiary care hospital. Critically ill patients were selected on the clinical suspicion of the presence of lactic acidosis. The inpatient mortality of the entire group was 14%, with a length of stay in hospital of 12 days and a length of stay in the ICU of 5.8 days. RESULTS: We reviewed records of 9,799 patients admitted to the ICUs at our institution between 1 January 2001 and 30 June 2002. We selected a cohort in which clinicians caring for patients ordered a measurement of arterial lactate level. We excluded patients in which any necessary variable required to characterize an acid-base disorder was absent. A total of 851 patients (9% of ICU admissions) met our criteria. Of these, 548 patients (64%) had a metabolic acidosis (standard base excess < -2 mEq/l) and these patients had a 45% mortality, compared with 25% for those with no metabolic acidosis (p < 0.001). We then subclassified metabolic acidosis cases on the basis of the predominant anion present (lactate, chloride, or all other anions). The mortality rate was highest for lactic acidosis (56%); for strong ion gap (SIG) acidosis it was 39% and for hyperchloremic acidosis 29% (p < 0.001). A stepwise logistic regression model identified serum lactate, SIG, phosphate, and age as independent predictors of mortality. CONCLUSION: In critically ill patients in which a measurement of lactate level was ordered, lactate and SIG were strong independent predictors of mortality when they were the major source of metabolic acidosis. Overall, patients with metabolic acidosis were nearly twice as likely to die as patients without metabolic acidosis.

Acidosis↗
PubMed1976

[The importance of lactate acidosis as a side effect of biguanide therapy].

A survey of the literature leads to the conclusion that lactic acidosis should be considered as a side effect of therapy with biguanides. Essential for the development of lactic acidosis seems to be the preexistence or the acute development of renal insufficiency. However, the over-dosage (for instance in the case of attempted suicide) causes acidosis (lactic acidosis) in healthy persons also. Using the experimental animal lactic acidosis is demonstrated following biguanide application. Diagnosis of lactic acidosis is substantiated by acidosis with lactic acid concentrations higher than 8-10 meq/l (= 72-90mg/100 ml) and with considerably increased lactate/pyruvate ratios (50-150). Generally a non ketotic acidosis of diabetic patients (especially under biguanide-therapy) should be considered to be a lactic acidosis. On the other hand the existence of lactic acid concentrations higher than 8-10 meq/l ist characteristic for a lactic acidosis. The prognosis of lactic acidosis induced by biguanides is not too good. Therapy of the acidosis using bicarbonate is not sufficient in most cases. The intravenous application of glucose (or glucose substitutes), perhaps with additional insulin, might be indicated by hypoglycemia. However, this therapy might cause an additional increase in lactic acid concentration. Treatment of choice might be dialysis, effecting the elimination of the biguanides. If peritoneal dialysis is performed acetate containing solutions should be used. Biguanide induced lactic acidosis is prevented by a very cautious selection of patients suited for biguanide therapy. The performance of renal function tests is absolutely necessary if therapy with biguanides is intended. Additionally, periodical control of renal function is required in patients treated with biguanides (at least twice a year). Biguanide therapy should be performed only with extreme caution, because decrease in renal function is very common in older patients.

Acidosis↗
PubMed2003

Persistent non-gastrointestinal metabolic acidosis in pediatric HIV-1 infection.

OBJECTIVES: To determine the incidence and to identify the clinical parameters associated with non-gastrointestinal renal tubular and high anion gap acidosis in a cohort of HIV-1-infected children. METHODS: Records of 202 HIV-1-infected children were reviewed to identify patients with metabolic acidosis. Serum and urine chemistries of those children with persistent non-gastrointestinal acidosis were then studied prospectively. Serum and urinary anion gaps (SAG and UAG) were calculated. Those with acidosis (group 1) were compared with children without acidosis (group 2). Associations were determined with Pediatric HIV classification, height, weight, antiretroviral therapy, and Pneumocystis carinii pneumonia prophylaxis. RESULTS: Persistent acidosis was noted in 34 out of 202 children (17%): 16 out of 34 (47%, group 1A) had elevated SAG acidosis, and 18 out of 34 (53%) had normal SAG acidosis with a positive UAG (distal renal tubular) acidosis (group 1B). Those with acidifying defects more often received P. carinii pneumonia prophylaxis (P = 0.02 and 0.01 for groups 1 and 1A, respectively) independently of HIV-1 classification. This group was shorter in height than group 2 (P = 0.007). Differences in weight were not significant (P = 0.1). However, acidotic subjects were more immunocompromised than those in group 2 (multivariate P < 0.001 for HIV classification C3). CONCLUSIONS: Elevated SAG acidosis and renal tubular acidosis are not uncommon among HIV-infected children with advanced disease. These disorders may be associated with height growth failure and prophylaxis with sulfur/sulfone containing antibiotics. HIV infection and/or its associated therapies may cause renal tubular damage. The causes of elevated SAG acidosis require further investigation.

AIDS-Related Opportunistic Infections↗
PubMed2004

Biochemistry of exercise-induced metabolic acidosis.

The development of acidosis during intense exercise has traditionally been explained by the increased production of lactic acid, causing the release of a proton and the formation of the acid salt sodium lactate. On the basis of this explanation, if the rate of lactate production is high enough, the cellular proton buffering capacity can be exceeded, resulting in a decrease in cellular pH. These biochemical events have been termed lactic acidosis. The lactic acidosis of exercise has been a classic explanation of the biochemistry of acidosis for more than 80 years. This belief has led to the interpretation that lactate production causes acidosis and, in turn, that increased lactate production is one of the several causes of muscle fatigue during intense exercise. This review presents clear evidence that there is no biochemical support for lactate production causing acidosis. Lactate production retards, not causes, acidosis. Similarly, there is a wealth of research evidence to show that acidosis is caused by reactions other than lactate production. Every time ATP is broken down to ADP and P(i), a proton is released. When the ATP demand of muscle contraction is met by mitochondrial respiration, there is no proton accumulation in the cell, as protons are used by the mitochondria for oxidative phosphorylation and to maintain the proton gradient in the intermembranous space. It is only when the exercise intensity increases beyond steady state that there is a need for greater reliance on ATP regeneration from glycolysis and the phosphagen system. The ATP that is supplied from these nonmitochondrial sources and is eventually used to fuel muscle contraction increases proton release and causes the acidosis of intense exercise. Lactate production increases under these cellular conditions to prevent pyruvate accumulation and supply the NAD(+) needed for phase 2 of glycolysis. Thus increased lactate production coincides with cellular acidosis and remains a good indirect marker for cell metabolic conditions that induce metabolic acidosis. If muscle did not produce lactate, acidosis and muscle fatigue would occur more quickly and exercise performance would be severely impaired.

Acidosis↗
PubMed1982

Interaction of acidosis and increased extracellular potassium on action potential characteristics and conduction in guinea pig ventricular muscle.

We studied the individual and combined effects of extracellular acidosis and increases in extracellular potassium on action potential characteristics and conduction in order to gain a better understanding of the effects of acute ischemia. At each level of potassium between 2.7 and 17 mm, acidosis induced by increasing Pco2 (respiratory acidosis) and by decreasing HCO3- (metabolic acidosis) decreased resting membrane potential, the maximum rate of rise of the action potential upstroke (Vmax), and slowed conduction. Metabolic acidosis consistently and significantly lengthened the steady state action potential duration whereas respiratory acidosis did not. Respiratory acidosis caused changes in resting membrane potential, Vmax, and conduction velocity; which occurred more rapidly and were of greater magnitude than the changes induced by metabolic acidosis. The changes in Vmax induced both types of acidosis were due to a change in the resting membrane potential-Vmax relationship as well as to the changes in the resting membrane potential. The conduction slowing induced by acidosis was greater when potassium was 9 and 13 mM than when potassium was 5.4 mm. Our results suggest that acidosis causes important changes in the electrophysiological properties of ventricular fibers and that many of the known electrophysiological effects of acute ischemia can be mimicked by the combined effects of extracellular acidosis and an increase in extracellular potassium.

Acidosis↗
PubMed2001

Clinical significance of the fractional excretion of anions in metabolic acidosis.

The fractional excretion of anions has been proposed as a new index for the differential diagnosis of metabolic acidosis, identifying the properties of the conjugate base by examining the renal handling of the anion. Here, we investigated clinical significance of the fractional excretion of anions in pathophysiologic diagnosis of metabolic acidosis by measuring urine ammonium (NH4+) excretion, the ratio of A plasma anion gap/delta plasma HCO3- concentration (deltaAG/deltaHCO3-), and fractional excretion of anions in three different groups of metabolic acidosis: acid overproduction (8 patients with lactic acidosis, 8 with diabetic ketoacidosis, 3 with hippuric acidosis following glue sniffing), acid underexcretion (10 patients with chronic renal failure) and normal controls (10 normal volunteers who underwent 3-day NH4Cl loading). As expected, urine NH4+ excretion was higher in overproduction acidosis than in acid-loaded normal controls (88.1 +/- 12.3 vs. 54.0 +/- 3.7 mmol/day, p < 0.05), and it was lower in chronic renal failure than in acid-loaded normal controls (12.8 +/- 1.7 vs. 54.0 +/- 3.7 mmol/day, p < 0.05). The fractional excretion of anions had no difference between overproduction acidosis and chronic renal failure (41.2 +/- 42.8% vs. 41.0 +/- 8.1%). However, the fractional excretion of anions showed significant differences between the subgroups in acid overproduction (lactic acidosis, 4.7 +/- 0.3%; diabetic ketoacidosis, 45.8 +/- 3.1%; hippuric acidosis, 126.0 +/- 14.4%; p < 0.05). The ratio of plasma deltaAG/deltaHCO3- also exhibited significant differences between the subgroups in acid overproduction (lactic acidosis, 1.5 +/- 0.1; diabetic ketoacidosis, 1.0 +/- 0.1; hippuric acidosis, 0.3 +/- 0.1; p < 0.05). There was an inverse linear correlation between the fractional excretion of anions and the ratio of plasma deltaAG/deltaHCO3- (r2 =-0.89, p < 0.05). In conclusion, determination of the fractional excretion of anions may provide a useful clue to the differential diagnosis of metabolic acidosis caused by acid overproduction.

Acidosis↗
PubMed1980

Changes in renal metabolite profile and ammoniagenesis during acute and chronic metabolic acidosis in dog and rat.

Acute metabolic acidosis was induced by an i.v. administration of hydrochloric acid to dogs and rats to decrease the plasma bicarbonate concentration from 22 to 12 mM in dogs and from 26 to 10 mM in rats. Chronic metabolic acidosis was also induced in dogs by ammonium chloride feeding for 5 days. Rats also were given ammonium chloride for 24 hours. The renal metabolite profile was determined on the freeze-clamped renal tissue before and after 100 min (dogs) or 30 to 240 min (rats) of acsute acidosis. Measurements on chronically acidotic dogs and rats with 24-hour acidosis were obtained also for comparison with acute acidosis. In both species, kidney glutamine, glutamate, and alpha-ketokglutarate concentrations decreased drastically following induction of acute or chronic acidosis, In the dog, or in the rat during the first 2 hours of acidosis, malate concentration was unchanged. Malate concentration fell significantly in the rat kidney only after 2 hours of acidosis without change in phosphoenolpyruvate (PEP) concentration. In chronically acidotic dogs, malate and oxaloacetate rose fivefold with no change in PEP concentration. Phosphoenolpyruvate carboxykinase (PEPCK) activity was not stimulated by chronic metabolic acidosis in the dog in contrast to the rat. Acute acidosis by hydrochloric acid increased net renal glutamine extraction in the rat but not in the dog. These data suggest that an increased metabolic flux occurs between alpha-ketoglutarate and malate in both rat and dog kidney during acute metabolic acidosis. In the rat, however, after 2 hours, PEPCK activation modifies the kidney metabolite profile. Intrarenal glutamine transport seems to be a rate-limiting factor for adaptation to acute acidosis in the dog but not in the rat kidney.

Acidosis↗
PubMed1983

Right ventricular performance during increased afterload impaired by hypercapnic acidosis in conscious dogs.

Since heart failure may occur in the setting of lung dysfunction and CO2 retention with only modest increases in cardiac work load, we questioned whether myocardial function is impaired by hypercapnic acidosis. To determine the influence of hypercapnic acidosis on right ventricular function, we measured the effects of acute (2 hours) and chronic (2 weeks) hypercapnic acidosis on right ventricular performance during normal and increased right ventricular afterload in five conscious dogs. Systemic hemodynamic and right ventricular functions were unaltered during normal right ventricular afterload by acute hypercapnic acidosis (PaCO2 = 49 +/- 3 mm Hg, pH = 7.27 +/- 0.003). As right ventricular afterload was increased by progressive balloon occlusion of the right ventricular outflow tract during acute hypercapnic acidosis, the rise (slope) in right ventricular end-diastolic pressure was increased 4-fold (P less than 0.01) over that observed in normocapnic control. Maximum isovolumic right ventricular dP/dt rose (P less than 0.05) comparably with increasing right ventricular afterload during normocapnic control and acute hypercapnic acidosis. Chronic hypercapnic acidosis (PaCO2 = 55 +/- 2 mm Hg, pH = 7.28 +/- 0.01) resulted in systemic vasodilation and increased (P less than 0.05) heart rate and cardiac output during normal right ventricular afterload. As right ventricular afterload was increased during chronic hypercapnic acidosis, the rate of rise in right ventricular end-diastolic pressure was 2-fold (P less than 0.01) above normocapnic control but maximum isovolumic right ventricular dP/dt was unchanged in contrast to normocapnic control and acute hypercapnic acidosis. Moreover, cardiac output fell and stroke work was unchanged with increasing afterload during chronic hypercapnic acidosis. beta-Adrenergic blockade resulted in an increased (P less than 0.01) rate of rise in right ventricular end-diastolic pressure with afterload during normocapnic control and chronic hypercapnic acidosis. We conclude that hypercapnic acidosis results in diminished right ventricular performance during increased right ventricular afterload, evidenced by accentuated rise in right ventricular end-diastolic pressure, and may contribute to the congestive heart failure and edema observed in patients with pulmonary hypertension and CO2 retention.

Acidosis, Respiratory↗
PubMed1997

Effects of anoxia, acidosis and temperature on the contractile properties of turtle cardiac muscle strips.

The responses to anoxia and acidosis of cardiac ventricular muscle strips from the anoxia-tolerant turtle Chrysemys picta bellii were investigated at 10 degrees C and 20 degrees C. Force-velocity curves were determined by quick isotonic releases at 85% of the time to peak isometric force under control, anoxia, lactate acidosis and anoxic lactate acidosis conditions. The isotonic forces during quick releases spanned 5-95% of the measured isometric force at each conditions. Superfusion solution pH was 7.8 and 7.95 for non-acidosis experiments, and 7.0 and 7.15 for acidosis experiments, at 20 degrees C and 10 degrees C, respectively. After normalizing force data to control isometric force, the values of maximum isometric force (P0), maximum velocity of shortening (Vmax) and maximal power output (Powermax) were evaluated by fitting the curves using the hyperbolic Hill equation. The maximum rate of force development (dF/dtmax), time-to-peak force (TPF) and half-relaxation time (T1/2) were also determined. At 20 degrees C, during acidosis, anoxia and anoxic acidosis, P0 decreased significantly to 81%, 40% and 24% of control values, dF/dtmax decreased significantly to 67%, 53% and 23% of control values, and Powermax decreased significantly to 75%, 40% and 14% of control values, respectively. Vmax, however, was not significantly affected by acidosis, anoxia or even anoxia acidosis. TPF was significantly shortened by anoxia, but prolonged by acidosis. The effects were similar at 10 degrees C, Temperature did not affect P0, but Vmax decreased by a factor of 1.6-1.8 at all corresponding conditions when temperature was reduced from 20 degrees C to 10 degrees C. We conclude that acidosis and anoxia inhibit isometric force production and Powermax of turtle cardiac muscle, but have no effect on Vmax, and the insensitivity of Vmax indicates that the rate of cross-bridge cycling is not affected by these conditions. Our observations indicate that the reduced power outputs of the hearts of submerged anoxic turtles at low temperature are due in part to inhibition of force production by anoxia and acidosis, and to a reduction of contraction velocity at low temperature.

Acidosis, Lactic↗