Central nervous system hyperammonemia

Ammonia is produced by all tissues during the metabolism of a variety of compounds, and it is disposed of primarily by formation of urea in he liver. However, the level of ammonia in the blood must be kept very fcw, because even slightly elevated concentrations (hyperammonemia) ae toxic to the central nervous system (CNS). There must, therefore, be a metabolic mechanism by which nitrogen is moved from peripheral tissues to the liver for ultimate disposal as urea, while at the same hre low levels of circulating ammonia must be maintained. 

One unexpected finding was that the plasma ammonia level appeared to increase as a result of zinc deficiency. We have reported similar findings in zlnc-deflclent rats (16). This may have important health implications concerning zinc deficiency In man, because in liver disease hyperammonemia is believed to affect the central nervous system adversely. 

Animal and human studies have shown that an elevated concentration of ammonia (hyperammonemia) exerts toxic effects on the central nervous system. There are several causes, both inherited and acquired, of hyperammonemia. The inherited deficiencies of urea cycle enzymes are the major cause of hyperammonemia in infants. The two major inherited disorders are those involving the metabolism of the dibasic amino acids lysine and ornithine and those involving the metabolism of organic acids, such as propionic acid, methylmalonic acid, isovaleric acid, and others (see Chapter 55). 

The acquired causes of hyperammonemia are advanced liver disease and renal failure. Severe or chronic liver failure (as occurs in fiilminant hepatitis and cirrhosis, respectively) leads to a significant impairment of normal ammonia metabolism. Reye s syndrome, which is primarily a central nervous system disorder with minor hepatic dysfunction, is also associated with hyperammonemia. Hepatic en-... 

Spectrum of consequences of defects in fatty acid oxidation. The primary effect is inadequate production of acetyl-CoA, which leads to decreased flux through the TCA cycle and lack of ketone body synthesis in the liver. Both of these events cause energy deficits and changes in metabolic regulatory processes. Alterations in hepatic metabolism lead to hypoglycemia and hyperammonemia. Abnormalities also occur in skeletal and cardiac muscle and in the central nervous system. 

The symptoms of acute intoxication may be very similar to that of other diseases (Box 5.3), may often lead to a misdiagnosis and, at times, death. On the other hand, some metabolic disorders can predispose a neonate to frequent neonatal period complications such as infections like E. coli sepsis in children with galactosemia or hematological complications such as central nervous system hemorrhage in hyperammonemia or thrombocytopeiua due to bone marrow suppresion in some aminoacidurias [2,7],... 

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