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Metabolic alkalosis with paradoxic aciduria in cattle.

In 4 cases of metabolic alkalosis with paradoxic aciduria in cattle, generalized muscle weakness was the predominant feature. In 3 of the 4 cases, prolonged anorexia preceded development of muscle weakness and aciduria. Plasma electrolyte concentrations varied but, in 3 of 4 cases, a transient decrease in plasma potassium concentration was detected. In the 3 cases in which prolonged therapy with sodium chloride, potassium chloride, and dextrose was offered, resolution of aciduria was rapid, followed by correction of metabolic alkalosis and return of muscle strength.

Acid-Base Imbalance↗

[Characteristics of the effects of artificial alkalosis on electrical activity of the brain and ultrastructure of blood cells in oncologic patients].

The authors examined 40 patients with malignant tumors of various histogenesis, sites and extent, as well as 5 patients with benign tumors and other non-tumorous diseases. They also studied their electroencephalography and peripheral blood lymphocytic and erythrocytic ultrastructure in metabolic alkalosis temporarily induced by intravenous sodium hydrogen carbonate. In cancer patients without late metastases, alkalosis caused a transient normalization of previously altered electroencephalography, erythrocyte disaggregation and substantially reduced the count of killer cells in small and middle lymphocytes. These findings suggest that patients with malignant neoplasms have a generalized intracellular acidosis which can be temporarily abolished by plasma alkalinization.

Adult↗

Excretion of HCO3- by the urinary bladder of Bufo marinus in metabolic alkalosis.

We studied the role of the urinary bladder of Bufo marinus in the excretion of bicarbonate into the urine. The toads were in metabolic alkalosis, produced by administering 120 mM NaHCO3 by stomach tube or by soaking the toads in 120 mM NaHCO3 solution for 48 to 72 hr. In vitro 10 cannulated whole bladders from toads in alkalosis transported bicarbonate from the serosal to mucosal medium. The average gradient created by this transport was 5.7 meq/1. In 15 whole bladders from toads in metabolic acidosis studied under identical conditions, there was no transport of bicarbonate into mucosal medium.

Alkalosis↗

Transepithelial pH gradients in cortical distal tubules during metabolic alkalosis.

1. The cortical distal tubule of the rat kidney participates in the regulation of acid-base balance, showing bicarbonate reabsorption, secretion or absence of transport under different experimental conditions. In the present study, we measured differences in transepithelial pH using double ion-exchange resin/reference microelectrodes in control and alkalotic (chronic plus acute) male Wistar rats and in alkalotic rats receiving a K+ supplement in diet and infusion. 2. pH was measured in the tubule lumen during stationary microperfusion with 25 mM bicarbonate Ringer solution, and in peritubular vessels next to the perfused tubules. 3. Differences in transepithelial pH were 0.70 +/- 0.12 (N = 16) pH units in early distal tubules (ED) and 1.03 +/- 0.050 (N = 15) in late distal tubules LD) of control rats, 0.22 +/- 0.056 (N = 17) in ED and 0.25 +/- 0.050 (N = 20) in LD of alkalotic rats, and -0.02 +/- 0.039 (N = 24) in ED and -0.02 +/- 0.040 (N = 24) in LD of K(+)-supplemented alkalotic rats. 4. In control rats, the transepithelial potential difference (PD) (-8.9 +/- 1.45 mV (N = 16) in ED and -32.7 +/- 2.99 mV (N = 15) in LD) was not large enough to explain transepithelial H+ and HCO3- gradients, suggesting the presence of an active transport mechanism responsible for their maintenance. 5. The present data show that the cortical distal tubule is able to establish transepithelial pH (HCO3-) differences, that these differences are reduced by alkalosis and abolished by alkalosis plus K+ supplementation, and that, although inversion of pH gradients (evidence for bicarbonate secretion) was observed in individual tubules, this inversion was not significant in the groups studied.

Acid-Base Equilibrium↗

Comparison of 0.9, 3.6, and 7.2% NaCl for correction of experimentally induced hypochloremic, hypokalemic metabolic alkalosis in sheep.

Nine adult female sheep were each surgically fitted with an Ivan and Johnston reentrant cannula in the cranial part of the duodenum just distal to the pylorus. By diversion (loss) of abomasal outflow, this model has been shown to consistently induce hypochloremic, hypokalemic metabolic alkalosis, accompanied by hyponatremia and dehydration. Each sheep was subjected to 3 treatment trials, each preceded by a 24-hour prediversion period, and a diversion period during which a syndrome of hypochloremia (68 +/- 2 mEq/L), hypokalemia, hyponatremia, and metabolic alkalosis was induced. Development of this syndrome was attributable to losses of large amounts of acid and electrolytes in the abomasal effluent. Mean total electrolyte contents of the effluent were: Cl-, 650 +/- 27 mEq; Na+, 388 +/- 23 mEq; and K+, 123 +/- 12 mEq, with total volume loss ranging from 3.6 to 10.0 L of gastric contents and pH ranging from 3 to 5. Decreases in plasma electrolyte concentrations also can be attributed to decreased intake, because anorexia developed shortly after the onset of diversion. Electrolyte losses in urine during diversion were minimal for Cl- (mean +/- SEM, 12.0 +/- 5.1 mEq), but were greater for Na+ (124.2 +/- 14.5 mEq) and K+ (185.1 +/- 31.2 mEq). Treatments consisted of 0.9% NaCl (300 mosm/L), 3.6% NaCl (1,200 mosm/L), and 7.2% NaCl (2,400 mosm/L) administered over a 2-hour period, with the administered volume determined by the estimated total extracellular fluid Cl- deficit. Significant difference was not found among treatments, with all solutions resulting in return of clinicopathologic and physical variables to prediversion values within 12 hours of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Abomasum↗

[Indices of protein and nitrogen metabolism in newborn calves in experimental metabolic acidosis and alkalosis].

The content of indices of protein and nitrogen metabolism in the blood of newborn calves has been studied under the conditions of experimental metabolic acidosis and alkalosis. It has been found that the state of experimental metabolic acidosis of the calves for the first 36 hours of their life is accompanied by the decrease in the content of protein and its basic fractions. Under experimental metabolic alkalosis the concentration of the mentioned indices considerably grows, and it even exceeds physiological values. The obtained results also evidence for the considerable role of hemoglobin buffer system of the newborn calves in regulation of organism acid-base-state.

Acidosis↗

Genotype-phenotype correlations in normotensive patients with primary renal tubular hypokalemic metabolic alkalosis.

Among the different forms of hereditary renal tubulopathies associated with hypokalemia, metabolic alkalosis and normotension, two main types of disorders have been identified: Gitelman disease, which appears to be a homogeneous post-Henle's loop disorder, and Bartter syndrome, a heterogeneous Henle loop disorder. A specific gene has been found responsible for Gitelman disease, encoding the thiazide-sensitive Na-Cl cotransporter (TSC) of the distal convoluted tubule. From a phenotypic point of view the characteristic findings of this disease are hypocalciuria, hypomagnesemia and tetanic crises appearing during childhood or later. Many subjects are asymptomatic. At least three different genes have been shown to be responsible for Bartter syndrome, characterized by mutations in the proteins encoding respectively the bumetanide-sensitive Na-K-2Cl cotransporter, the inwardly-rectifying renal potassium channel and a renal chloride channel, all protein transports located in the ascending limb of Henle's loop. Mutations in the first two transport proteins have been demonstrated in patients with the hypercalciuric forms of Bartter syndrome associated with nephrocalcinosis (respectively Bartter syndrome type I and II), who were often born after pregnancies complicated by polyhydramnios and premature delivery. Mutations in the gene encoding a renal chloride channel were recently recognized in patients with a Henle tubular defect not associated with nephrocalcinosis (Bartter syndrome type III). Most of the latter group of patients were normo-hypercalciuric and presented dehydration and life-threatening hypotension in the first year of life. However, these three genes do not explain all the patients with Bartter syndrome which unlike Gitelman disease, appears to be a very heterogeneous disorder. Clearance studies, especially if done during furosemide and/or hydrochlorothiazide administration, have been helpful in identifying the site of tubular involvement. Considering both phenotypic and genotypic data, we propose a clinical-pathophysiological and molecular approach to diagnose the different tubulopathies associated with hypokalemic metabolic alkalosis.

Alkalosis↗

An atypical case of primary renal tubular hypokalaemic metabolic alkalosis with chronic tophaceous gout.

A 55-year-old woman was referred to our ward for further evaluation of marked hyperuricaemia and suspected tophi. On physical examination, huge subcutaneous nodules were observed on the knee joints as well as a small nodule on the lateral side of the left sole. Blood chemistry showed marked hyperuricaemia (0.85 mmol/l), hypokalaemia (2.7 mmol/l) and a mild degree of renal insufficiency. Arterial blood gas analysis showed signs of metabolic alkalosis. Daily urinary uric acid excretion on a purine non-restricted diet was 8.9 mmol/day. Uric acid clearance and fractional uric acid clearance were 0.8 ml/min and 2.6%, respectively. Plasma renin activity was 21.8 ng/ml/h, and plasma angiotensin II and aldosterone concentrations were 61 and 121 pg/ml, respectively. However, pressor response to an intravenous administration of angiotensin II was normal. The urinary calcium to creatinine molar ratio was 0.069, and serum magnesium concentration was normal to supranormal. A biopsy of the subcutaneous nodule showed a typical appearance of tophus. Based on these findings, the patient was diagnosed with an atypical case of renal tubular hypokalaemic metabolic alkalosis, with marked hyperuricaemia and tophi as the initial manifestations. So far, only four cases of Bartter's syndrome with gout and/or hyperuricaemia have been described in Japan. This rare case is presented and its mechanism of hyperuricaemia discussed.

Arthritis, Gouty↗

Recurrent metabolic alkalosis and elevated troponins after crack cocaine use in a hemodialysis patient.

When acid-base disorders have been described after cocaine use, they are usually metabolic acidosis. We report a case of recurrent crack cocaine use associated with severe metabolic alkalosis on two successive admissions, in a patient in renal failure on hemodialysis and with minimal urine output, despite no history of vomiting or alkali ingestion. The metabolic alkalosis did not recur after counseling and abstention from cocaine.

Acidosis↗

The effect of acidosis and alkalosis on in vitro aldosterone production.

There are conflicting data concerning the effect of hydrogen ion concentration (H+) on aldosterone production in vivo. This study examines the effect of changes in H+ on in vitro aldosterone production in isolated adrenal capsular cells of rats. The pH was adjusted to 7.1 or 6.8 using lactic acid and to 7.7 using sodium hydroxide. Potassium and other ions in the incubation medium were maintained at nearly constant levels. There was a significant decrease in aldosterone production when the pH was lowered from 7.4 to 7.1 or to 6.8 and also when the pH was increased to 7.7. This decrease was highly significant when measured in absolute terms or relative to ACTH-stimulated control samples included in each assay. Acidosis and alkalosis both decrease rather than stimulate aldosterone production in vitro and indicate that the observed in vivo stimulation of aldosterone by acidosis most likely is mediated by other aldosterone stimuli. These data also confirm that a marked alkalosis decreases aldosterone production and supports further study of changes in a more physiologic range.

Adrenal Glands↗

Effects of induced metabolic alkalosis on perception of dyspnea during flow-resistive loading.

Treatment of dyspnea in patients with advanced cancer is an important issue. The purpose of the present study was to assess the effect of induced-metabolic alkalosis produced by administration of sodium bicarbonate on dyspneic sensation. In seven healthy subjects, dyspnea was induced by having them breathe with a flow-resistive load (24 cm H2O/L/sec) for 6 min before and after administration of sodium bicarbonate (0.5 mmol/kg, per os+2 mmol/kg, IV). The intensity of dyspnea was rated using a visual analogue scale (VAS). The VAS scores and minute ventilation during loaded breathing after administration of sodium bicarbonate were significantly lower than those before administration of sodium bicarbonate. These results indicate that induced metabolic alkalosis may alleviate the intensity of dyspneic sensation by a reduction in ventilatory drive.

Adult↗

Correction of metabolic alkalosis by potassium chloride in ectopic adrenocorticotropic hormone syndrome.

A 57-year-old white man presented with metabolic alkalosis, hypokalemia (pH 7.58, HCO3 >50 mEq/L, serum K 1.8 mEq/L) and hypertension. The initial evaluation was significant for markedly elevated serum cortisol and adrenocorticotropic hormone (ACTH) level; neither hormone showed circadian rhythm or suppression with high-dose dexamethasone. Perihilar and supraclavicular masses were found to consist of undifferentiated small cell carcinoma. Ectopic ACTH syndrome was diagnosed. In spite of progressively rising hormone levels (ACTH, 723 pg/dL; and cortisol, 212 microgram/dL), his severe metabolic alkalosis was largely corrected by aggressive treatment with potassium chloride alone. Possible mechanisms of these clinical findings are discussed.

ACTH Syndrome, Ectopic↗

Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2.

Inherited hypokalaemic alkalosis with low blood pressure can be divided into two groups-Gitelman's syndrome, featuring hypocalciuria, hypomagnesaemia and milder clinical manifestations, and Bartter's syndrome, featuring hypercalciuria and early presentation with severe volume depletion. Mutations in the renal Na-Cl cotransporter have been shown to cause Gitelman's syndrome. We demonstrate linkage of Bartter's syndrome to the renal Na-K-2Cl cotransporter gene NKCC2, and identify frameshift or non-conservative missense mutations for this gene that co-segregate with the disease. These findings demonstrate the molecular basis of Bartter's syndrome, provide the basis for molecular classification of patients with inherited hypokalaemic alkalosis, and suggest potential phenotypes in heterozygous carriers of NKCC2 mutations.

Amino Acid Sequence↗

Maximal exercise tolerance after induced alkalosis.

Eight healthy males performed two rides to exhaustion at a work load corresponding to 125 VO2 max, 1 h after ingesting either 0.2 g NaHCO3/kg body weight (E) or NaCl (C). Mean +/- SE pre-exercise blood pH, HCO-3, and base excess (BE) values were respectively 7.42 +/- 0.01, 28.2 +/- 1.5 mmol/l, and 2.02 +/- 0.10 mmol/l for the E condition, and 7.39 +/- 0.01, 24.4 +/- 0.07 mmol/l, and -0.40 +/- 0.07 mmol/l for the C condition (P less than 0.05 for all variables). Cycling time to exhaustion (E = 100.6 +/- 6.1; C = 98.6 +/- 5.7 s) and total VO2 during recovery (E = 17.7 +/- 0.9; C = 17.3 +/- 0.8 1/30 min) did not differ significantly between treatments. Blood pH, HCO-3, and BE were significantly higher while the hydrogen ion to lactate ratio (nmol/mmol) was significantly lower in E than in C during recovery. Blood LA levels were also greater in E than in C during the latter part of recovery although peak individual values were not significantly different between trials (E = 14.4 +/- 0.4; C = 13.3 +/- 0.0 mmol/l). In view of the insignificant differences in cycling time, peak individual LA, and total recovery VO2, it is not likely that LA production was greater in E than in C. Rather it appears that LA efflux was enhanced by the NaHCO3 feeding. Additionally, the return of the acid-base status in blood to resting conditions was more rapid during alkalosis. Given this protocol, alkalosis does not help to sustain an intense exercise bout. These data suggest, however, that NaHCO3 may be of benefit following repeated work bouts.

Bicarbonates↗

Cerebral intracellular lactic alkalosis persisting months after neonatal encephalopathy measured by magnetic resonance spectroscopy.

We have found that cerebral lactate can be detected later than 1 month of age after neonatal encephalopathy (NE) in infants with severe neurodevelopmental impairment at 1 y. Our hypothesis was that persisting lactate after NE is associated with alkalosis and a decreased cell phosphorylation potential. Forty-three infants with NE underwent proton and phosphorus-31 magnetic resonance spectroscopy at 0.2-56 wk postnatal age. Seventy-seven examinations were obtained: 25 aged <2 wk, 16 aged > or = 2 to < or = 4 wk, 25 aged > 4 to < or = 30 wk, and 11 aged > 30 wk. Neurodevelopmental outcome was assessed at 1 y of age: 17 infants had a normal outcome and 26 infants had an abnormal outcome. Using univariate linear regression, we determined that increased lactate/creatine plus phosphocreatine (Cr) was associated with an alkaline intracellular pH (pHi) (p < 0.001) and increased inorganic phosphate/phosphocreatine (Pi/PCr) (p < 0.001). This relationship was significant, irrespective of outcome group or age at time of study. Between outcome groups, there were significant differences for lactate/Cr measured at < 2 wk (p = 0.005) and > 4 to < or = 30 wk (p = 0.01); Pi/PCr measured at < 2 wk (p < 0.001); pHi measured at < 2 wk (p < 0.001), > or = 2 to < or = 4 wk (p = 0.02) and > 4 to < or = 30 wk (p = 0.03); and for N-acetylaspartate/Cr measured at > or = 2 to < or = 4 wk (p = 0.03) and > 4 to < or = 30 wk (p = 0.01). Possible mechanisms leading to this persisting cerebral lactic alkalosis are a prolonged change in redox state within neuronal cells, the presence of phagocytic cells, the proliferation of glial cells, or altered buffering mechanisms. These findings may have implications for therapeutic intervention.

Brain↗

Effect of extracellular alkalosis upon calcium distribution within the B cells.

Insulin secretion and the pattern of calcium distribution in B cells, assessed with the pyroantimonate precipitation technique, were simultaneously studied in rat pancreases perfused with 3.3 and 16.6 mM glucose solutions of pH 7.4 and 7.8. We have previously demonstrated the blocking effect of the latter pH upon glucose-induced insulin secretion. Glucose (16.6 mM) caused an increase in the total number of calcium pyroantimonate precipitates (CPP), as well as their number bound to different B cell structures, at every sampling period studied, with respect to the 3.3 mM glucose experiments. Extracellular alkalosis strongly inhibited both phases of the B cell response to the glucose stimulus, and greatly affected the distribution of CPP in the cells with respect to the pH 7.4 ones. During the first phase of glucose induced-insulin secretion, most of the CPP appeared within B granules at pH 7.4, while on the development of the second phase of secretion, they appeared mainly attached to the cell plasma membranes. Conversely, in pH 7.8 experiments, at the first minutes of the glucose challenge, CPP appeared principally located in the cytoplasm, being almost absent from the plasma membrane during the second phase of insulin secretion. These observations suggest that during the glucose stimulus, the cell calcium distribution within the B cells followed a clear chronological sequence. Such sequence might be determined, at least in part, according to the different Ca2(+)-set points of the different B cell structures. In our case, the extracellular alkalosis might interfere with the normal intracellular calcium fluxes, which in consequence might impair release of insulin by affecting several B cell functions.

Acid-Base Equilibrium↗

Effect of acidosis and alkalosis on postischemic Ca gain in isolated rat heart.

The effect of pH of the reperfusion buffer on postischemic changes in tissue Ca and Na was examined in isolated Langendorff-perfused Sprague-Dawley rat hearts. Reperfusion began after 15-, 25-, or 60-min ischemia at 37 degrees C. After 60-min ischemia, reperfusion at pH 6.4 or 6.6 attenuated the reperfusion-induced Ca gain so long as the acidotic conditions were maintained (3.08 +/- 0.22, 1.37 +/- 0.41, and 16.96 +/- 1.18 mumol Ca gain/g dry wt for pH 6.4, 6.6, and 7.4, respectively after 15-min reperfusion). Conversely, reperfusion under alkalotic conditions (pH 7.9) after 60-min ischemia exacerbated the gain (27.45 +/- 4.75 and 8.92 +/- 1.53 mumol Ca gain/g dry wt during 5-min reperfusion at pH 7.9 and 7.4, respectively). Similar, but less pronounced Ca gains occurred during reperfusion after 15- or 25-min ischemia. Sodium content during reperfusion, but not during aerobic perfusion, was also found to be pH sensitive with acidosis causing a reduction and alkalosis an increase. These results could not be explained in terms of an effect of pH on recovery of high-energy phosphates, percentage "reflow" during reperfusion, or reperfusion-induced increases in tissue water or resting tension. The results are in agreement with the hypothesis that the "inhibitory" effect of acidosis on postischemic Ca overload could involve an effect of pH on the Na(+)-H+ exchanger and intracellular Ca storage.

Acidosis↗

Ketoacid production in acute respiratory and metabolic acidosis and alkalosis in rats.

Metabolic acidosis inhibits and alkalosis enhances ketoacid production in ketotic humans and animals. To compare these effects with those of superimposed respiratory acid-base disturbances, ketone output was evaluated in awake ketotic rats during metabolic (intravenous infusions of HCl or NaHCO3) or respiratory (hyper or hypocapnia) disorders. With decreases in blood pH of 0.1-0.2 units over 3 h, blood ketone concentrations significantly decreased an average of 1.9 mM (metabolic) and 1.1 mM (respiratory) and urinary ketone excretion rates significantly decreased by 1.3 mumol/min (metabolic). With increases in systemic pH, blood ketone concentrations and urinary ketone excretion rates were significantly increased. Changes in blood pH correlated with changes in urinary ketone excretion rates in both metabolic (r = 0.87) and respiratory (r = 0.67) acid-base disturbances. The alterations occurred promptly and were rapidly reversible. These findings indicate that modest changes in systemic pH from metabolic or respiratory acid-base disturbances modify net ketoacid production in ketotic rats, confirm pH control of endogenous acid output as an acid-base regulator, and show that systemic pH, not bicarbonate concentration, mediates the process.

Acetoacetates↗