Pathogenesis of Hepatic Encephalopathy-with Special Reference to the Role of Ammonia
01 May 1970-The American Journal of Clinical Nutrition (American Society for Nutrition)-Vol. 23, Iss: 5, pp 619-632
About: This article is published in The American Journal of Clinical Nutrition.The article was published on 1970-05-01. It has received 108 citations till now. The article focuses on the topics: Encephalopathy & Hepatic encephalopathy.
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TL;DR: The findings indicate that glia have a crucial role in glutamic acid, gamma-aminobutyric acid, and ammonia metabolism in brain.
Abstract: Light microscopy immunohistochemical techniques were used to examine the distribution of glutamine synthetase in rat brain. Glutamine synthetase was found to be localized in the glial cells. Neuronal cell bodies, endothelial cells, and choroid epithelium contained no enzyme. The findings indicate that glia have a crucial role in glutamic acid, gamma-aminobutyric acid, and ammonia metabolism in brain.
1,181 citations
TL;DR: In patients with portal-systemic shunting, muscle may become the most important organ for ammonia detoxification and contribute to the development of hyperammonemic encephalopathy with an associated increase in the brain ammonia utilization rate.
Abstract: 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.
376 citations
TL;DR: Greater emphasis on early detection of encephalopathy and aggressive treatment of minimal hyperammonemia may retard the development of ammonia-induced complications of severe liver disease and explain the emergence of toxin hypersensitivity as liver disease progresses.
Abstract: Cerebral ammonia metabolism was studied in five control subjects and five patients with severe liver disease exhibiting minimal hepatic encephalopathy The arterial ammonia concentration in the control subjects was 30 ± 7 μmol/L (mean ± SD) and 55 ± 13 μmol/L in the patients (p < 001) In the normal subjects, the whole-brain values for cerebral blood flow, cerebral metabolic rate for ammonia, and the permeability-surface area product for ammonia were 058 ± 012 ml g−1 min−1, 035 ± 015 μmol 100 g−1 min−1, and 013 ± 003 ml g−1 min−1, respectively In the patients, the respective values were 046 ± 016 ml g−1 min−1 (not different from control), 091 ± 036 μmol 100 g−1 min−1 (p < 0025), and 022 ± 007 ml g−1 min−1 (p < 005) The increased permeability-surface area product of the blood-brain barrier permits ammonia to diffuse across the blood-brain barrier into the brain more freely than normal This may cause ammonia-induced encephalopathy even though arterial ammonia levels are normal or near norm
319 citations
Cites background from "Pathogenesis of Hepatic Encephalopa..."
...Ammonia is the toxin that is the most studied and most clearly implicated in the pathogenesis of the disorder (Phear et aI. , 1955; Sherlock, 1958; Walker and Schenker, 1970; Duffy et aI. , 1974; Lockwood et aI. , 1979; Butterworth et aI. , 1987; Lockwood, 1987)....
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TL;DR: The majority of cirrhotic patients after portal-systemic shunt operations have demonstrable neuropsychological deficits, and the severity of impairment appears to be related more to status of nitrogen metabolism than to level of over-all hepatic function.
298 citations
TL;DR: Campylobacter pyloridis, a bacterium implicated as the aetiological agent of gastritis and possibly gastric ulcers, has a very high urease activity, which results in alterations in the milieu of the gastric epithelium preventing the normal passage of hydrogen ions and a predisposition to ulcer formation.
231 citations