Metabolic alkalosis, ammonia

Hypoventilation causes retention of C02 by the lungs, which can lead to a respiratory acidosis. Hyperventilation can cause a respiratory alkalosis. Metabolic acidosis can result from accumulation of metabolic acids (lactic acid or the ketone bodies p-hydroxybutyric acid and acetoacetic acid), or ingestion of acids or compounds that are metabolized to acids (methanol, ethylene glycol). Metabolic alkalosis is due to increased HC03, which is accompanied by an increased pH. Acid-base disturbances lead to compensatory responses that attempt to restore normal pH. For example, a metabolic acidosis causes hyperventilation and the release of C02, which tends to lower the pH. During metabolic acidosis, the kidneys excrete NH4+, which contains H+ buffered by ammonia. 

Excretion into urine of ammonia produced by renal mbu-lar cells facilitates cation conservation and regulation of acid-base balance. Ammonia production from intracellular renal amino acids, especially glutamine, increases in metabolic acidosis and decreases in metabolic alkalosis. 

Ammonia can diffuse freely into the urine through the tubule membrane, while the ammonium ions that are formed in the urine are charged and can no longer return to the cell. Acidic urine therefore promotes ammonia excretion, which is normally 30-50 mmol per day. In metabolic acidosis (e.g., during fasting or in diabetes mellitus), after a certain time increased induction of glutaminase occurs in the kidneys, resulting in increased NH3 excretion. This in turn promotes H"" release and thus counteracts the acidosis. By contrast, when the plasma pH value shifts towards alkaline values alkalosis), renal excretion of ammonia is reduced. 

The pH-buffering of extracellular fluid depends in part on the carbon dioxide/ bicarbonate equilibrium so that the intake of sodium bicarbonate is followed by a brief alkalosis and an increased excretion of sodium carbonate in the urine. Depending on its carbonate concentration, the pH of the urine may rise to 8.07. Large doses (80—100 g/day) of sodium bicarbonate were needed if the pH of stomach contents was to be maintained at 4 or over in patients with duodenal ulcers8. Oxidation of organic anions in the body to carbon dioxide and water permits the use of sodium citrate, lactate or tartrate instead of sodium bicarbonate. In an analogous manner the ingestion of ammonium chloride induces a brief acidosis as a result of the metabolic conversion of ammonia to urea and lowers the pH of the urine. 

Dog No. 3 was omitted because of insufficient data. It is apparent that a marked uptake of ammonia occurs in tissues in metabolic acidosis. In alkalosis the uptake by tissues is only slightly greater than normal, and the arterial levels of ammonia are comparable with normal values. The elevation of blood ammonia which occurs on vigorous acidification of the animal might not be due to a drop in permeability with pH, but might be due to a phenomenon reported by Krebs and Henseleit (K4). Urea synthesis by liver slices is directly proportional to the pH and C02 content of the medium. Table 2, constructed from data reported in this paper, shows this dependence. 

Ammonia arises in the body principally from the oxidative deamination of amino acids. In addition to its uptake in the reactions mentioned above, ammonia is also excreted in the urine as ammonium salts. This is not derived directly from the blood ammonia but is formed by the kidney from glutamine by the action of glutaminase. In metabolic acidosis, ammonia production and excretion by the kidney is greatly increased, and conversely it is decreased in metabolic alkalosis. This may be an important means of excreting excess ammonia. It must be remembered that ammonia formed by the action of intestinal bacteria on the protein hydrolyzates in the intestine can be also absorbed. The contribution of the ammonia formed in this way to the total ammonia in the body is unknown. Since this ammonia drains into the portal circulation, it is promptly removed by the liver. 

A second report (H4) concerned a female infant who was hospitalized at 20 days of age because of difficulty in feeding, lethargy, and convulsions. Two sibs had died with similar symptoms at 4 weeks of age, but two other sibs were normal. Blood ammonia levels on a relatively low protein intake (1.5 g/kg/day) ranged between 25 and 100 /ig/lOO ml, and blood urea between 2 and 14 mg/100 ml. Her general condition improved on the low protein diet, but later it deteriorated and she died at 7 2 months of age, weighing little more than her birth weight of 3.25 kg. Liver function tests were normal there was a slight metabolic alkalosis. 

The carbonic anhydrase inhibitors cause metabolic acidosis and urinary alkalosis. Patients with severe impairment of liver function are unahle to synthesize urea efficiently and become dependent on renal excretion of ammonium ion to rid the body of nitrogenous wastes. However, in alkaline urine the ammonium ion is rapidly converted to ammonia gas. which is veiy rapidly reabsorbed. Hyperammonemia results, with severe neurologic consequences. The answer is (A). 

As a metabolic organ, the K. is responsible for the constancy of the acid-base balance of the body. The normal pH of the blood is 7.4, and it is important that this value is not increased (see Alkalosis) or decreased (see Acidosis). The K. contains amine oxidases and glutaminase, which catalyse the production of free ammonia. In acidosis these reactions are brought into play and excess H ions are consumed by formation of NH In addition to the natural secretory processes foreign substances such as pharma-... 

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