Liver metabolic disorders

Insulin is a peptide hormone, secreted by the pancreas, that regulates glucose metabolism in the body. Insufficient production of insulin or failure of insulin to stimulate target sites in liver, muscle, and adipose tissue leads to the serious metabolic disorder known as diabetes mellitus. Diabetes afflicts millions of people worldwide. Diabetic individuals typically exhibit high levels of glucose in the blood, but insulin injection therapy allows diabetic individuals to maintain normal levels of blood glucose. 

While ammonia, derived mainly from the a-amino nitrogen of amino acids, is highly toxic, tissues convert ammonia to the amide nitrogen of nontoxic glutamine. Subsequent deamination of glutamine in the liver releases ammonia, which is then converted to nontoxic urea. If liver function is compromised, as in cirrhosis or hepatitis, elevated blood ammonia levels generate clinical signs and symptoms. Rare metabolic disorders involve each of the five urea cycle enzymes. 

Acute and chronic viral, bacterial, microbial and parasitic infections, skin disease, metabolic disorders, chronic liver disease and kidney disease. 

Glycogen metabolism disorders Amylo-l,6-glucosidase defect Liver phosphorylase defect Glycogen synthetase defect... 

During conversion of ethanol to acetaldehyde, hydrogen ion is transferred from alcohol to the cofactor nicotinamide adenine dinucleotide (NAD+) to form NADH. As a net result, alcohol oxidation generates an excess of reducing equivalents in the liver, chiefly as NADH. The excess NADH production appears to underlie a number of metabolic disorders that accompany chronic alcoholism. 

D-Penicillamine 26 (Figure 2.8) has for long time been used for the treatment of Wilson s disease, a metabolic disorder in which absorbed copper is deposited mainly in the liver and in the brain. Long-term application of this compound leads to suppression of rheumatoid arthritis, which now is its main therapeutic use [3],... 

Table 3.5 Examples of inherited and metabolic disorders resulting in liver disease...

SAFETY PROFILE Contact with hot coolant can cause severe damage to lungs, skin, and eyes from burns. May cause chronic damage to liver, kidney, and blood-forming organs metabolic disorders. Inhalation has caused bronchopneumonia. When heated to decomposition they emit acrid smoke and fumes. 

Another metabolic disorder that is hereditary and little known is hypophosphatasia. Hypophosphatasia is an inherited metabolic (chemical) bone disease that results from low levels of an enzyme called alkaline phosphatase (ALP). ALP is normally present in large amounts in bones and the liver. In hypophosphatasia, abnormalities in the gene that makes ALP lead to the production of inactive ALP. Subsequently, several chemicals, including phosphoethanolamine, pyridoxal 57-phosphate (a form of vitamin B ) and inorganic pyrophosphate, accumulate in the body and are found in large amounts in the blood and urine. It appears that the accumulation of inorganic pyrophosphate is the cause of the characteristic defective calcification of bones seen in infants and children (rickets) and in adults (osteomalacia). 

Hepatic coma can be subdivided according to its aetiology as follows (7.) hepatocyte disintegration coma (= endogenous coma as a result of the loss of parenchyma), (2.) liver cell failure coma (= exogenous coma as a result of metabolic disorders, almost always in the presence of cirrhosis), (3.) electrolyte coma (= so-called false coma due to dyselectrolytaemia, almost always iatrogenic), and (4.) mixed forms of coma. (s. pp 214, 276, 381) (s. tab. 15.5)... 

Indications for the transplantation of hepatocytes predominantly involve those liver diseases in which functional failures occur in the liver cells (not in the bile ducts). Permanent transplantation would be indicated, for example, in order to eliminate congenital metabolic disorders of the liver cells. In this case, hepatocytes from the patient could be used, with subsequent elimination of the defect by gene technology, as well as hepatocytes from healthy donors. A few years ago, a therapeutic effect lasting for over one year was achieved for the first time in a girl suffering from the Crigler-Najjar syndrome (I. X Fox et af, 1998). Human hepatocytes are most definitely more suitable than animal liver cells. The latter may well meet the requirements for a provisional substitute, but not for permanent transplantation. 

Endogenous hepatosis comprises endogenous metabolic disorders of the liver cell as a rule, the terminology used in this context refers to the accumulated substances (e. g. glycogenosis), the harmful substrate (e.g. fructose-1 phosphate) or the enzyme defect (e.g. apantitrypsin deficiency). 

Fulminant or protracted liver failure is caused by medicaments in 10-15% of cases. A reduction in the functional liver mass to < 20-35% is deemed to be a critical stage. However, the death of the patient may already occur due to secondary metabolic disorders (so-called exogenous hepatic coma) before the extent of the parenchymal loss has fallen below the critical threshold (so-called endogenous hepatocellular disintegration coma), (s. tab. 29.10)... 

Primary metabolic disorders and storage diseases are caused by endogenous factors, usually a gene mutation. Since the congenital defect is predominantly or exclusively located in the liver, the resulting diseases also become manifest in this organ. 

Secondary metabolic disorders and storage diseases are present in almost all liver diseases and occur with more or less pronounced intensity. They are, however, also caused by faulty nutrition as well as by many exogenous factors or noxae - just as latent metabolic disorders may generally become manifest due to such factors. 

In primary or secondary metabolic disorders or storage diseases, almost all metabolic functions of the liver may be affected. 

Causes of fatty liver are manifold, and combinations of causes quite common. Acquired causes are by far the most frequent, but there are also rare causes, e.g. coeliac disease (9, 25), parenteral nutrition. (28, 29) Congenital metabolic disorders can also lead to the development of a fatty liver, as in the case of a rare thesaurismosis. It is of considerable therapeutic and prognostic importance to differentiate between an alcoholic fatty liver (AFL) and alcoholic steatohepatitis (ASH) (s. pp 529, 531) as well as between non-alcoholic fatty liver (NAFLD) and non-alcoholic steatohepatitis (NASH). (2, 20, 24, 36) (s. tabs. 31.5-31.7)... 

Disorders of lipid metabolism, particularly type IV (endogenous hypertriglyceridaemia), cause fatty liver to develop. Hyperlipidaemia is present in ca. 50% of patients with sonographically determined fatty liver. (2, 56) Likewise, patients suffering from gout are very often found to have fatty liver. Both these metabolic disorders frequently appear in combination with obesity. 

Hepatic encephalopathy is a metabolic disorder characterized by a wide spectrum of neuropsychiatric dysfunction. It may occur as an acute syndrome in patients with acute hepatic failure from viral or drug-induced hepatitis or as a chronic syndrome associated with liver failure and cirrhosis. 

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