The Kidney as a Source of Blood Ammonia in Patients With Liver Disease: The Effect of Acetazolamide *†

Owen, Edward E.; Tyor, Malcolm P.; Flanagan, John F.; Berry, John N.

doi:10.1172/jci104039

Cited by 68 publications

(35 citation statements)

References 17 publications

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“…The differences noted, however, between peripheral artery and renal vein are comparable to those reported by other investigators for normal individuals and for patients with liver disease who were not subjected to acid loading (27)(28)(29). In addition, as noted above, the administration of calcium chloride orally had no measurable effect upon arterial blood ammonium concentrations.…”

Section: Resultssupporting

confidence: 86%

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Relation of Acute Potassium Depletion to Renal Ammonium Metabolism in Patients With Cirrhosis*

Baertl¹,

Sancetta²,

Gabuzda³

1963

J. Clin. Invest.

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Neurologic findings characteristic of the impending hepatic coma syndrome occur in some cirrhotic patients treated with diuretic agents that may induce potassium losses (1-5). Even when diuretic agents are not employed, hypokalemia may be associated with this syndrome (6-8). Patients demonstrating these signs often improve after treatment with potassium salts. This result of therapy might indicate that potassium deficiency per se is a pathogenetic factor in the impending hepatic coma syndrome (9). Because of the extensive evidence relating abnormalities in nitrogen metabolism to hepatic coma (10), however, it seemed possible that some derangement of nitrogen metabolism might be associated with potassium deficiency.This hypothesis, relating potassium deficiency indirectly to the hepatic coma syndrome by an influence this cation has on ammonium metabolism, provided the rationale for undertaking this investigation. The relation of potassium to ammonium metabolism was studied in patients with cirrhosis of the liver and ascites rendered acutely potassium deficient by a diuretic regimen. The results of these studies demonstrate that metabolism of ammonium by the kidney is altered in potassium-deficient patients and that significant quantities of ammonium may be delivered to the cir-* A preliminary report of this investigation was included in the proceedings of the American Association for Study of Liver Disease, Chicago, 1959 (Gastroenterology 1960, 38, 803).

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Section: Resultssupporting

confidence: 86%

“…Thus, the mechanisms involved here are apparently different from those that occur after the administration of acetazolamide. This agent produces a bicarbonate diuresis, prompt increase in urine pH, and diversion of ammonium from urine into renal venous outflow (29).…”

Section: Discussionmentioning

confidence: 99%

Relation of Acute Potassium Depletion to Renal Ammonium Metabolism in Patients With Cirrhosis*

Baertl¹,

Sancetta²,

Gabuzda³

1963

J. Clin. Invest.

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“…To our knowledge there is only one other study in patients with cirrhosis that studied this and reported exactly the same results in their 5 patients. 13 Urinary ammonia excretion is an important way of releasing circulating ammonia and/or nitrogen during liver failure, as we showed earlier. 14,32 In postabsorptive healthy rats, 70% of total renal ammoniagenesis is released into the systemic circulation, whereas in rats with acute and chronic liver failure 70% of total renal ammoniagenesis was excreted into urine and 30% was released into the renal vein.…”

Section: Discussionmentioning

confidence: 63%

Interorgan ammonia and amino acid metabolism in metabolically stable patients with cirrhosis and a TIPSS

et al. 2002

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Ammonia is central to the pathogenesis of hepatic encephalopathy. This study was designed to determine the quantitative dynamics of ammonia metabolism in patients with cirrhosis and previous treatment with a transjugular intrahepatic portosystemic stent shunt (TIPSS). We studied 24 patients with cirrhosis who underwent TIPSS portography. Blood was sampled and blood flows were measured across portal drained viscera, leg, kidney, and liver, and arteriovenous differences across the spleen and the inferior and superior mesenteric veins. The highest amount of ammonia was produced by the portal drained viscera. The kidneys also produced ammonia in amounts that equaled total hepatosplanchnic area production. Skeletal muscle removed more ammonia than the cirrhotic liver. The amount of nitrogen that was taken up by muscle in the form of ammonia was less than the glutamine that was released. The portal drained viscera consumed glutamine and produced ammonia, alanine, and citrulline. Urea was released in the splenic and superior mesenteric vein, contributing to whole-body ureagenesis in these cirrhotic patients. In conclusion, hyperammonemia in metabolically stable, overnight-fasted patients with cirrhosis of the liver and a TIPSS results from portosystemic shunting and renal ammonia production. Skeletal muscle removes more ammonia from the circulation than the cirrhotic liver. Muscle releases excessive amounts of the nontoxic nitrogen carrier glutamine, which can lead to ammonia production in the portal drained viscera (PDV) and kidneys. Urinary ammonia excretion and urea synthesis appear to be the only way to remove ammonia from the body.

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“…It has been clearly shown, however, that acute increases in urine pH following carbonic anhydrase inhibition (3,26) or metabolic alkalosis (18) are associated with rapid increases in ammonia released into renal veins, a rapid decrease in urine ammonia excretion, and an essentially unchanged total bidirectional release. These changes appear to occur irrespective of the level of control arterial ammonia concentration.…”

Section: Methodsmentioning

confidence: 99%

“…Previous observations in this laboratory and in others have demonstrated that the kidney consistently releases ammonia into the systemic circulation of normal subjects and patients with liver disease whose arterial ammonia concentrations are normal (1)(2)(3)(4)(5). Patients with liver disease and moderate to marked hyperammonemia, however, usually release minimal quantities of ammonia into their renal veins and occasionally exhibit renal uptake of ammonia from the circulation (2).…”

mentioning

confidence: 92%

The Effect of Induced Hyperammonemia on Renal Ammonia Metabolism*†

Owen¹,

Johnson²,

Tyor³

1961

J. Clin. Invest.

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Although the excretion of ammonia into urine has been extensively studied, there is little information in animals or man concerning the quantitative and regulatory aspects of the ammonia released into the renal veins. Previous observations in this laboratory and in others have demonstrated that the kidney consistently releases ammonia into the systemic circulation of normal subjects and patients with liver disease whose arterial ammonia concentrations are normal (1-5). Patients with liver disease and moderate to marked hyperammonemia, however, usually release minimal quantities of ammonia into their renal veins and occasionally exhibit renal uptake of ammonia from the circulation (2). -In order to further define the possible role of the blood ammonia concentration on renal ammonia release, acute hyperammonemia has been induced in normal subjects and the subsequent changes in renal vein ammonia release and urine ammonia excretion determined. METHODSNine patients without hepatic or renal disease were studied. All were hospitalized ambulatory males ranging in age from 28 to 49 years. Subj ects were studied in the recumbent position after an overnight fast. In order to initiate a water diuresis, 1,000 to 1,500 ml of water was ingested 30 minutes to 1 hour before each procedure. A constant intravenous infusion (Bowman pump) which delivered 14 to 18 mg of para-aminohippurate (PAH) per minute was maintained throughout the study period and was preceded by a priming dose calculated to provide plasma levels of approximately 2 mg per 100 ml. The water diuresis was maintained throughout the procedure by the intravenous infusion of 5 per cent dextrose and water at a rate of 15 to 20 ml per minute. Arterial samples were obtained from a brachial artery and renal venous samples from the * This investigation was supported (in part) by a research grant (Public Health Service A-3255) from the National Institutes of Health, Bethesda, Md. tThis paper was presented (in part) at the Southern Society for Clinical Research, New Orleans, La., January 23, 1960. right renal vein by way of a no. 8 catheter. Control voided urine specimens were collected during and after equilibration of the PAH infusion. Baseline arterial and renal venous samples were begun 45 to 60 minutes after the PAH infusion was started. Each patient received an intravenous infusion of 0.155 M ammonium lactate at a rate of 0.50 mEq of ammonia per minute for 30 minutes and 0.75 mEq of ammonia per minute for the subsequent 15 minutes. Serial arterial-renal venous ammonia differences were obtained at 15-minute intervals during the infusion and at the 15 minute post-infusion period. Voided urine samples collected in an oil-toluene mixture were obtained at 15-to 30-minute intervals during the infusion and in 4 subjects for 30 to 60 minutes after the infusion was terminated.Blood and urine ammonia was measured by a modification (6) of the microdiffusion method of Brown, Duda, Korkes and Handler (7). PAH concentration in blood and infusion media was determined by the method...

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The Kidney as a Source of Blood Ammonia in Patients With Liver Disease: The Effect of Acetazolamide *†

Cited by 68 publications

References 17 publications

Relation of Acute Potassium Depletion to Renal Ammonium Metabolism in Patients With Cirrhosis*

Relation of Acute Potassium Depletion to Renal Ammonium Metabolism in Patients With Cirrhosis*

Interorgan ammonia and amino acid metabolism in metabolically stable patients with cirrhosis and a TIPSS

The Effect of Induced Hyperammonemia on Renal Ammonia Metabolism*†

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