Liver hepatic functional capacity

The liver is also the principal metabolic center for hydrophobic amino acids, and hence changes in plasma concentrations or metabolism of these molecules is a good measure of the functional capacity of the liver. Two of the commonly used aromatic amino acids are phenylalanine and tyrosine, which are primarily metabolized by cytosolic enzymes in the liver [1,114-117]. Hydroxylation of phenylalanine to tyrosine by phenylalanine hydroxylase is very efficient by the liver first pass effect. In normal functioning liver, conversion of tyrosine to 4-hy-droxyphenylpyruvate by tyrosine transaminase and subsequent biotransformation to homogentisic acidby 4-hydroxyphenylpyruvic acid dioxygenase liberates CO2 from the C-1 position of the parent amino acid (Fig. 5) [1,118]. Thus, the C-1 position of phenylalanine or tyrosine is typically labeled with and the expired C02 is proportional to the metabolic activity of liver cytosolic enzymes, which corresponds to functional hepatic reserve. Oral or intravenous administration of the amino acids is possible [115]. This method is amenable to the continuous hepatic function measurement approach by monitoring changes in the spectral properties of tyrosine pre- and post-administration of the marker. 

Newer and potentially better hepatic function index continues to captivate researchers. A recent report indicates that hippurate ratio is a good measure of functional hepatocyte capacity [13]. The procedure monitors the conjugation of glycine to p-aminobenzoic acid by liver enzymes and may provide unique information on functional hepatic reserve. 

Rodent KC and HC, as well as human HC, express an inducible NO synthase under septic or inflammatory conditions. In vivo in endotoxemia, this expression is transient. Our in vivo data indicate that this induced -NO serves a protective role in the liver and reduces hepatic injury in endotoxemia. This protective action may be mediated by the capacity of NO to neutralize oxygen radicals and prevent platelet adherence and aggregation. Our in vitro studies show that HC-derived -NO can activate soluble guanylate cyclase. Other in vitro effects include the nonspecific suppression of protein synthesis and a small reduction in mitochondrial aconitase activity. The relevance of these in vitro actions to hepatic function in vivo remains to be determined. 

Autoimmune hepatitis typically occurs in females, at puberty and between the ages of 40 and 70. It can also occur in males at any age. It may present in a number of ways as a mild hepatitis, as a severe acute hepatitis or as established cirrhosis. The functioning capacity of the liver will vary depending on the stage of disease. The diagnosis of AIH is based on serum biochemistry, liver histology, and the presence of certain autoantibodies in the serum. Exclusion of other potential causes of hepatitis, e.g. hepatitis B or C, alcohol consumption, is needed before a definitive diagnosis can be made. There are no featnres that are specifically indicative of AIH, but it usually responds to treatment with corticosteroids. Once remission is indnced azathioprine or... 

Within a certain degree of hepatocellular damage, liver cell functions remain completely or widely intact at least, no impaired partial functions are yet detectable under clinical conditions. As liver damage progresses, however, numerous cellular functions become increasingly affected, so that clinically relevant disorders become evident. Thus impairment of the hepatic excretory capacity can be taken as a criterion of parenchymal damage. 

Coagulation factors are proteins with varying but usually short half-lives, (s. tab. 5.12) Their determination allows the assessment of hepatic function. However, the respective half-life has to be considered. Disorders of coagulation factors are therefore important functional parameters in hepatic diseases - both in severe acute and in chronic cases. In liver diseases, there may be a lack of coagulation factors, which is predominantly and primarily caused by a disorder of the hepatocyte synthesis capacity. This lack can also be due to other causes (1.) accelerated catabolism, (2.) altered biosynthesis of inhibitors, (3.) production of abnormal factors, and (4.) increased demand due to intravasal coagulation. 

The galactose test assesses the ability of the hepatocyte to convert galactose to glucose. A healthy liver possesses a capacity to metabolize 500-600 mg galactose per minute. Roughly 90% of parenterally administered galactose is metabolized in the liver - independently of hepatic perfusion. Galactose elimination capacity (GEC) correlates well with the viable liver cell volume (67) and is therefore referred to as a reliable measure of the metabolic function of the liver. Prior to determination of GEC, 24-hour alcohol abstinence is necessary. (50, 53, 55, 65, 67, 69, 71, 72, 75, 77, 82)... 

The liver rapidly absorbs from 10 to 20% of dietary folate, with a preference for non-methylated and non-reduced derivatives, while peripheral tissues are enriched in reduced and methylated functional derivatives. Folate is mainly stored in the liver. Hepatic folates are partly excreted into the bile enterohepatic circulation and reabsorbed (Steinberg et al. 1979). This is one of the mechanisms involved in the recirculation of folate. Regarding renal elimination, folate is filtered by the glomerulus and reabsorbed into the proximal tubule. The daily urinary excretion of intact folates is between 1 to 12 pg. When the serum plasma folate concentration is very high, it is possible to overwhelm the renal reabsorption capacity in this case, folate derivatives are excreted in the urine. Due to the possible production by the gut microflora, fecal folate levels are quite high. 

Generally, the liver is the center of drug metabolism, hence numerous drugs and methods to measure functional hepatic capacity are available. A host of these methods rely on the metabolic activity of cytochrome P450 enzymes, and some of the markers used include phenacetin, methacetin, trimethadione. 

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