Effect of acute acidosis and alkalosis on leucine kinetics in man.

The effects of acute pH changes on whole body leucine kinetics (1-13C-leucine infusion technique) were determined in normal subjects. Plasma insulin, glucagon, and growth hormone concentrations were kept constant by somatostatin and replacement infusions of the three hormones. When acidosis was produced by ingestion of NH4Cl (4 mmol kg-1 p.os; n = 8) arterialized pH decreased within 3 h from 7.39 +/- 0.01 to 7.31 +/- 0.01 (P less than 0.001) and leucine plasma appearance increased by 0.13 +/- 0.04 mumol kg-1 min-1 (P less than 0.02); in contrast, when alkalosis was produced by intravenous infusion of 4 mmol kg-1 NaHCO3 (n = 7, pH 7.47 +/- 0.01), leucine plasma appearance decreased by -0.09 +/- 0.04 mumol kg-1 min-1 (P less than 0.01 vs. acidosis). Whole body leucine flux also increased during acidosis compared to alkalosis (P less than 0.05), suggesting an increase in whole body protein breakdown during acidosis. Apparent leucine oxidation increased during acidosis compared to alkalosis (P = 0.05). Net forearm leucine exchange remained unaffected by acute pH changes. Plasma FFA concentrations decreased during acidosis by -107 +/- 67 mumol l-1 (P less than 0.05) and plasma glucose increased by 1.90 +/- 0.25 mmol l-1 (P less than 0.02); in contrast, alkalosis resulted in an increase in plasma FFA by 83 +/- 40 mumol l-1 (P less than 0.02; P less than 0.01 vs. acidosis), suggesting an increase in lipolysis; plasma glucose decreased compared to acidosis (P less than 0.01). The data demonstrate that acute metabolic acidosis and alkalosis, as they occur in clinical conditions, influence protein breakdown, and in the opposite direction, lipolysis.     

Effect of arsenite on renal tissue slice metabolism in chronic metabolic acidosis and alkalosis.

Tissue slices prepared from renal cortex of littermate dogs with chronic metabolic acidosis or alkalosis were incubated in media with or without arsenite and containing 1 mM L-[14C]glutamine or [1,5-14C]citrate. The presence of arsenite increased the concentration of alpha-ketoglutarate in slices by 5--20 times the values found without this inhibitor. alpha-Ketoglutarate concentrations in acidotic slices were 40% or more greater than those in alkalotic ones when arsenited was present. 14C incorporation into alpha-ketoglutarate was also increased manyfold by arsenite with either labeled glutamine or citrate as substrate. 14CO2 production from labeled glutamine by over 90% and from labeled citrate by over 75%; the difference between 14CO2 production by acidotic and alkalotic slices was greatly reduced or eliminated by arsenite. These results suggest that in chronic metabolic acidosis metabolism of both glutamine and citrate is stimulated at a site or sites preceding formation of alpha-ketoglutarate.     

Pancreatic tissue pH in experimental acidosis and alkalosis

The pH was studied in pancreatic tissue and arterial blood in 22 dogs. Respiratory acidosis was induced by CO2 inhalations in 5 dogs, respiratory alkalosis by hyperventilation in 5 dogs, metabolic acidosis by intravenous(i.v.) infusion of 0.1 N HCl in 5 dogs, metabolic alkalosis by i.v. infusion of 4.2% Na bicarbonate in 5 dogs. The differences between the shifts of blood pH and tissue pH were not significant statistically. Infusion of Ringer's solution failed to affect the pH in blood and pancreatic tissue in two control animals. It is concluded, that with an adequate tissue blood flow the pancreatic tissue pH is uninformative unless the blood pH is known.     

Pre-HD dilution acidosis,without post-HD contraction alkalosis in uremic patients

The aim of this study was to verify if the degree of pre-HD acidosis and its correction post-HD is related to body fluid expansion during the interdialytic period. Twelve uremic patients without major problems, with stable hematocrit, with regular and similar HD-session characteristics, but widely varying amounts of body fluid expansion in the interdialytic period were included. Blood samples were collected from arterial line pre- and post-HD, anaerobically in heparinized syringes, for determination of HCO3-, pH and PaCO2 (radiometer Copenhagen ABL 300 Acid-Base Laboratory), in two similar HD-sessions for each patient (12 patients, 24 HD-sessions). The percentage (%) of body weight gain in the interdialytic period was also estimated. For each patient, the mean value of parameters studied in the two HD-sessions was used for the evaluation of findings. According to mean values (+/-SD) of HCO3-, pH and PaCO2 Pre-HD (18.26+/-1.99 mmol/L, 7.31+/-0.03, 36.27+/-2.5 mmHg respectively) and post-HD (26.37+/-1.7, 7.43+/-0.03, 38.43+/-2.10 respectively) patients are acidotic pre-HD and slightly alkalemic post-HD. Correlation between the percentage (%) of interdialytic body weight gain (IBWG) and the values of HCO3-, pH and PaCO2, Pre-HD (r=-0.814, p<0.001; r=-0.931, p<0.001; r=0, 100 NS; respectively) and post-HD (r=-0.958, p<0.001; r=-0.937, p<0.001; r=-0.504 NS; respectively) indicates a significant and negative relationship of IBWG% with HCO3- and pH pre- and post-HD, but not with PCO2. In conclusion, the negative relationship of IBWG% with HCO3- and pH pre- and post-HD indicates that the body fluid expansion during the interdialytic period contributes to a dilutional acidosis pre-HD, but not to a contraction alkalosis post-HD, by the elimination of fluid during the HD-session.     

Acid-base changes in the brain in nonrespiratory acidosis and alkalosis

Summary Changes in the bicarbonate and the chloride concentrations in the brain, as well as in the bicarbonate concentration of the cisternal cerebrospinal fluid (CSF), were measured in rats made acidotic or alkalotic for a period of 6 hours by means of intraperitoneal injections of acid and basic solutions. The difference in the plasma chloride concentrations between the acidotic and the alkalotic groups was 8.6 mEq/l, while the corresponding difference in the tissue concentrations was 4.5 mEq/kg of wet tissue. These results demonstrate that the chloride ion equilibrated between the plasma and the chloride space of the brain tissue under the conditions of the experiments. However, although the marked difference in the plasma bicarbonate concentrations between the same groups (17.4 mEq/l) was accompanied by a difference in the CSF bicarbonate concentrations of 7.6 mEq/kg, there were no significant differences in the actual tissue bicarbonate concentrations, attributable to the extracellular bicarbonate changes. Provided that CSF is representative of the extracellular fluid (ECF), these results can either be interpreted to show that the bicarbonate of the ECF is distributed in a very small tissue compartment (probably less than 5 per cent of the tissue volume), or that nonrespiratory acid-base changes are not accompanied by net fluxes of bicarbonate ions between the plasma and the extracellular space of the brain tissue but rather by redistributions of bicarbonate ions between extra-and intracellular fluids.The technical assistance of Mrs. Ingrid Glantz and Mrs. Inga-Maj Markinger is greatefully acknowledged.     

Calcium and acidosis in renal hypoxia

The effects of lowering extracellular calcium concentration on hypoxic injury in the thick ascending limb of Henle (TAL) were studied in the isolated perfused rat kidney. At standard conditions of pH 7.4 and total perfusate calcium 1.9 mM, widespread TAL necrosis results from the combined effects of low medullary O2 delivery and the demands of solute transport activity. Reducing calcium to 0.5 or 0.1 mM, effectively prevented TAL membrane fragmentation. This cytoprotection was not accompanied by improved O2 delivery or by any consistent effects on renal physiology (glomerular filtration rate, sodium reabsorption, free water clearance or O2 consumption) that might have suggested that the mechanism was reduced O2 demand. In addition, the medullary ATP depletion which characteristically precedes TAL necrosis was not reversed. Finally, reduced perfusate calcium also markedly decreased TAL damage in an alternative model of hypoxia-like injury caused by a respiratory uncoupler. In aggregate, these findings indicate that reducing extracellular calcium does not prevent hypoxia itself, but rather disrupts the mechanism of its effects on cell integrity. The relationship of H+ and Ca2+ in the pathogenesis of hypoxic TAL injury was also studied. Lowering media pH to 7.0 reduced TAL damage but this cytoprotection was overcome by increasing media calcium concentration. Furthermore, with more severe acidosis (media pH 6.5 or 6.0), progressively greater perfusate calcium concentrations were required to reproduce severe TAL damage. These results indicate that extracellular calcium promotes the development of hypoxic TAL necrosis and that the cytoprotective effect of acidosis in hypoxia may be to counteract the calcium-dependent mechanism of injury.     

Effect of regional hypoxia and blood flow on capillary permeability in canine myocardium

The effect of hypoxia and blood flow on the capillary permeability-surface area product (PS) of ⁵¹Cr-EDTA was investigated in canine myocardium of open chest anesthetized dogs at constant aortic pressure, heart rate, and cardiac output. PS was determined by bolus injection of ⁵¹Cr-EDTA into the left anterior descending coronary artery (LAD) and external registration of the response curve. Vascular conductance (G) and PS were measured: (1) during pump perfusion of LAD with arterial blood (control state), and (2) during vasodilation obtained by LAD perfusion with deoxygenated blood at same blood flow as in control state, and (3) during increased blood flow with deoxygenated blood. Mean value of G in control state was 1.31 ml. min^-l. (100 g)^-1 (mmHg)^-1. The ratio G-hypoxialG-control used to assess the extent of vasodilation was 2.42 (range 1.67–3.56) during hypoxia and unchanged flow and 2.82 (range 1.81447) during hypoxia and increased flow. Mean value of PS in control state was 36 ml. (100 g)^-1. min^-1. With maximum vasodilation and constant blood flow PS increased to 47.3 ml.(100 g)-¹.min-¹ (37%) and during increased blood flow to 69.0 ml.(100 g)^-1. min^-1 (96%). The increase in PS most likely reflects an increase in capillary surface area available for exchange of ⁵¹Cr-EDTA indicating a 1.4– to 2-fold recruitment of capillaries.     

Acid-base changes in milk and blood of rats in acidosis and alkalosis.

Lactating white rats (Rattus norvegicus) were subjected to metabolic and respiratory acidosis and metabolic alkalosis. Before and during the various treatments, the acid-base status of heart blood and milk was determined. Acute metabolic acidosis lowered the pH of plasma and milk; Pco(2) and bicarbonate concentrations in plasma were lowered, and in milk Pco(2) was raised and the bicarbonate concentration remained unchanged. Respiratory acidosis and acetazolamide caused a drop in blood pH and in blood and milk bicarbonate concentrations; milk pH remained unchanged, but Pco(2) was raised in both plasma and milk. Acute metabolic alkalosis raised the blood pH and milk Pco(2); plasma Pco(2) and bicarbonate concentrations in blood and milk remained unchanged. The data show that greater changes occur in acid-base parameters of blood than milk when animals are exposed to acidifying and alkalinizing stimuli.