Effect of starvation on renal metabolism in the rat

The effects of starvation an the acid base status of the rat and on the gluconeogenic and ammoniagenic capacity of rat renal-cortical slices were examined. Starvation for 48 or 72 hrs did not affect acid-base status, and urinary ammonia production did not change. Kidney cortical slices from starved as compared to fed rats showed increased gluconeogenic capicity when incubated with the substrated pyruvate, succinate, fumarate, malate, 2-oxoglutarate, glutamine and glutamate. Renal cortical tissues from starved rats also had increased activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase. Renal cortical slices from starved rats did not differ from those of fed rats in the ability to produce ammonia from glutamine or glutamate, nor was there any difference in the activity of glutaminase between these groups. These results show that renal gluconeogenic capacity is increased in starved rats in the absence of systemic acidosis, and starvation does not lead to an increase in urinary ammonia excretion or renal ammoniagenic capacity. (AU)

Environmental temperature and response to premedicant drugs

A total of 105 subjects have been studied, 70 in the hot climate of Jamaica and 35 in the temperate climate of England. Following the same premedication a very significant alteration from resting levels in the arterial pH and PaCO3 occurred in the subjects in Jamaica, but there was no change in the Jamaican and English groups in England. This sensitivity was shown to be related to a lowereing of the metabolic rate in the hot climate. There was no relationship to race, liver disease, or immediate ambient room temperature (AU)

Acid-base balance in adults with sickle cell anaemia

This study of acid-base balance in adults with sickle cell anaemia was undertaken because of the reports of severe metabolic acidosis during "Painful Crisis". Metabolic acidosis has been incriminated as the cause of the "Painful Crisis" and it has been claimed that alkali treatment can prevent and even abort these painful episodes. It was therefore possible that a defect in urinary acidification could explain this tendency to develop acidosis with its serious consequences. The results of acid-base parameters during the steady state showed a mild respiratory alkalosis which is a non-specific finding in patients with severe anaemia. The response to oral NH4Cl loading revealed a slight but significant defect in urinary acidification (minimum pH in SCA 5.38 against 4.83 for controls). Titratable Acid excretion was reduced but the urinary NH4+ though reduced was normal when related to the urine pH. The glomerular filtration rate was normal. These findings are compatible with the syndrome of Incomplete Renal Tubular Acidosis. The administration of oral neutral phosphate resulted in a marked increase in titratable acid excretion but the defect in urinary acidification persisted. A maximal acidifying stimulus (Na2SO4 infusion) produced intense urinary acidification in both normal controls (minimum pH 4.55) and patients with SCA (minimum pH 4.59). Since the sulfate infusion is a known test of distal tubular acidification, a gradient type defect (Distal RTA) was ruledout. The threshold for bicarbonate excretion was reduced in 3 of 6 patients and it was therefore suggested that these patients have a form of Proximal Renal Tubular Acidosis due to defective bicarbonate reabsorption. There was no evidence of metabolic acidosis during "Painful Crisis". This would suppport our belief that Alkalis are of little use in the treatment or prevention of "Painful Crises", at least in our population (AU)

Acid-base status of adults with sickle-cell anaemia

Determinations of the acid-base status of 10 adult Jamaican patients with sickle-cell anaemia during "painful crisis" and after recovery showed no evidence of metabolic acidosis in the former, in contrast to reports from elsewhere. These results could explain the failure of alkalis to abort or alter the acute painful episodes of most patients with sickle-cell anaemia (AU)

Renal metabolic response to acid base changes : I enzymatic control of ammoniagenesis in the rat

Experiments were done on rats to investigate the nature of the renal response to metabolic acidosis and the changes in enzyme activity associated with increased ammoniagenesis. When metabolic acidosis was induced with oral feeding of ammonium chloride for 48 hr, there was an increase of activity of the enzyme phosphoenolpyruvate carboxykinase (PEPCK) in whole kidneys as well as in the kidney cortex. There was no change in PEPCK in liver, and glucose-6-phosphatase showed no change in kidney or liver in response to metabolic acidosis. The increase in PEPCK activity in kidney cortex varied with the degree of acidosis and there was a close correlation between cortical PEPCK activity and urinary ammonia. Kidney cortex mitochondrial PEPCK did not change in response to metabolic acidosis. An increase in PEPCK occurred as early as 6 hr after NH4Cl feeding, before there was any increase in kidney glutaminase I activity. Rats fed sodium phosphate, or given triamcinolone intramuscularly, developed a metabolic alkalosis, but there was increased urinary ammonia and an increase in activity of renal cortical PEPCK. Triamcinolone plus ammonium chloride induced a greater increase of PEPCK activity than triamcinolone by itself; on the contrary, the rise of glucose-6-phosphatase induced by triamcinolone was not enhanced by acidosis. Glucose-6-phosphatase from control and acidotic rats had identical kinetic characteristics. The results indicate that increased PEPCK activity is constantly related to increases of urinary ammonia. It is proposed that the increase of PEPCK activity is the key event in the ammoniagenesis and gluconeogenesis which follow on metabolic acidosis. (AU)

Electrolyte and acid-base disturbances occurring in infantile gastro-enteritis in Jamaica

A preliminary investigation of electrolyte and acid-base disturbances occurring in infantile gastroenteritis in Jamaica is presented. As associated malnutrition was common it is felt the clinical assessment of dehydration remains more relible than laboratory methods in such cases. True hypertonicity was rare and so was hypocalcemia. Hypopotassemia was common but never associated with paralytic illness. A low serum magnesium level was common but usually asymptomatic. In four instances however, it apparently produced serious symptoms with potentially fatal possibilities. We therefore feel that magnesium supplements should be given along with potassium and other electrolytes in the crystalloid replacement therapy of such cases (AU)