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The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia.

Publication ,  Journal Article
Lockwood, AH; McDonald, JM; Reiman, RE; Gelbard, AS; Laughlin, JS; Duffy, TE; Plum, F
Published in: J Clin Invest
March 1979

The cyclotron-produced radionuclide, 13N, was used to label ammonia and to study its metabolism in a group of 5 normal subjects and 17 patients with liver disease, including 5 with portacaval shunts and 11 with encephalopathy. Arterial ammonia levels were 52-264 micron. The rate of ammonia clearance from the vascular compartment (metabolism) was a linear function of its arterial concentration: mumol/min = 4.71 [NH3]a + 3.76, r = +0.85, P less than 0.005. Quantitative body scans showed that 7.4 +/- 0.3% of the isotope was metabolized by the brain. The brain ammonia utilization rate, calculated from brain and blood activities, was a function of the arterial ammonia concentration: mumol/min per whole brain = 0.375 [NH3]a - 3.6, r = +0.93, P less than 0.005. Assuming that cerebral blood flow and brain weights were normal, 47 +/- 3% of the ammonia was extracted from arterial blood during a single pass through the normal brains. Ammonia uptake was greatest in gray matter. The ammonia utilization reaction(s) appears to take place in a compartment, perhaps in astrocytes, that includes less than 20% of all brain ammonia. In the 11 nonencephalopathic subjects the [NH3]a was 100 +/- 8 micron and the brain ammonia utilization rate was 32 +/- 3 mumol/min per whole brain; in the 11 encephalopathic subjects these were respectively elevated to 149 +/- 18 micron (P less than 0.01), and 53 +/- 7 mumol/min per whole brain (P less than 0.01). In normal subjects, approximately equal to 50% of the arterial ammonia was metabolized by skeletal muscle. In patients with portal-systemic shunting, muscle may become the most important organ for ammonia detoxification. Muscle atrophy may thereby contribute to the development of hyperammonemic encephalopathy with an associated increase in the brain ammonia utilization rate.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

March 1979

Volume

63

Issue

3

Start / End Page

449 / 460

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Radionuclide Imaging
  • Nitrogen Radioisotopes
  • Middle Aged
  • Metabolic Clearance Rate
  • Male
  • Liver Diseases
  • Kinetics
  • Immunology
  • Humans
 

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Lockwood, A. H., McDonald, J. M., Reiman, R. E., Gelbard, A. S., Laughlin, J. S., Duffy, T. E., & Plum, F. (1979). The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. J Clin Invest, 63(3), 449–460. https://doi.org/10.1172/JCI109322
Lockwood, A. H., J. M. McDonald, R. E. Reiman, A. S. Gelbard, J. S. Laughlin, T. E. Duffy, and F. Plum. “The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia.J Clin Invest 63, no. 3 (March 1979): 449–60. https://doi.org/10.1172/JCI109322.
Lockwood AH, McDonald JM, Reiman RE, Gelbard AS, Laughlin JS, Duffy TE, et al. The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. J Clin Invest. 1979 Mar;63(3):449–60.
Lockwood, A. H., et al. “The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia.J Clin Invest, vol. 63, no. 3, Mar. 1979, pp. 449–60. Pubmed, doi:10.1172/JCI109322.
Lockwood AH, McDonald JM, Reiman RE, Gelbard AS, Laughlin JS, Duffy TE, Plum F. The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. J Clin Invest. 1979 Mar;63(3):449–460.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

March 1979

Volume

63

Issue

3

Start / End Page

449 / 460

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Radionuclide Imaging
  • Nitrogen Radioisotopes
  • Middle Aged
  • Metabolic Clearance Rate
  • Male
  • Liver Diseases
  • Kinetics
  • Immunology
  • Humans