Hepatic enzymes alkaline phosphatase

In general, transaminases are only mildly increased, and deep jaundice combined with mild elevation of liver enzymes should raise the suspicion for fulminant Wilson disease. However, increases of transaminases may be indistinguishable from findings seen in acute hepatitis. Sometimes alkaline phosphatase activities are relatively low in patients with Wilson disease. A ratio of total serum bilirubin concentration and alkaline phosphatase activity (>2) may differentiate fulminant Wilson disease from other forms of fulminant hepatic failure. However, the usefulness of this test was not confirmed in larger series. 

The Group II (biliary tract) enzymes are abnormal usually when the serum bilirubin concentration is also abnormal. Most commonly used is alkaline phosphatase which is a highly sensitive indicator of biliary tract obstruction, perhaps because the enzyme is synthesized as an induced response to obstruction of even small bile ducts. Most techniques used to identify the origin of an elevated serum alkaline phosphatase are not very useful from a clinical viewpoint (23). The simultaneous measurement of GMT activity has been found to be useful in differentiating between the hepatic and bony origin of alkaline phosphatase. An increased GMT activity in a patient with an increased ALP activity is a good indication that there is biliary biliary tract disease (62,63). 

Acute hepatic injury In rare instances, symptoms consistent with acute hepatic injury, as well as significant elevations in enzymes such as alkaline phosphatase, CPK, LDH, AST, and ALT have occurred with diltiazem and nifedipine. 

Adverse reactions occurring in at least 3% of patients included the following abnormal vision, alkaline phosphatase increased, ALT/AST increased, chills, fever, hallucinations, headache, hepatic enzymes increased, liver function test abnormal, nausea, peripheral edema, photophobia, rash, vomiting. 

In the study of N. A. Gorchakova et al, Enterosgel was used for the treatment of fulminant hepatitis in rats caused by administration of tetrachloromethane [25], It was noted that enterosorption hampered hpid peroxidation in hver tissue of experimental animals, elevated activity of enzymes of the antioxidant pool and decreased activity of serum transaminases, which indicates better preservation of hepatocyte membranes. O.R. Grek et al, used multiple administrations of CCl in combination with drinking of 5% ethanol for modeling of chronic hepatitis in rats. They demonstrated a stable positive effect of Enterosgel administration on activity of serum transaminases and alkaline phosphatase, as well as the rate of hepatic metabolism of xenobiotics [26]. 

In a retrospective review of 497 patients taking propylthiouracil for hyperthyroidism, clinically overt hepatitis developed in six patients at 12-49 days after starting the drug (50). Jaundice and itching were present in five, fever in two, rash in two, and arthralgia in one. Serum bilirubin, alanine transaminase, and alkaline phosphatase were increased in five, four, and six patients respectively. The type of hepatic injury was cholestatic in three, hepatocellular in one, and mixed in two. There were no differences in age, sex, drug dose, or serum thyroid hormone concentrations at time of diagnosis in those with hepatic injury compared with those without. Liver function normalized in all patients at 16-145 days after withdrawal of propylthiouracil. In addition to these cases of overt liver injury, 14% of the cohort had mild asymptomatic liver enzyme rises at a mean of 75 days after the start of treatment. 

Hepatic Effects. A study that measured levels of several liver enzymes (alanine amino transferase, aspartate amino transferase, gamma glutamyl transferase, and alkaline phosphatase) found no significant differences between workers exposed to silver and insoluble silver compounds and those with no history of silver exposure (Pifer et al. 1989). 

Attempts have been made to develop noninvasive tests that might provide more specific information about the site of injury. For example, excretion of enzymes in urine may reflect renal injury. Urinary excretion of enzymes of renal origin (enzymes that are specific to the kidney, such as maltase, y-glutamyl transpeptidase, or treha-lase) could indicate specific destruction of renal proximal tubules, whereas alkaline phosphatase in urine could arise from renal or prerenal (e.g., hepatic) damage (Figure 29.7). 

In about 50% of cases, hepatitis mononucieosa with hepatomegaly (10-25%) develops, displaying an increase in transaminases of 10-20 times the normal value. (13, 15) Jaundice is witnessed in 5-10% of cases, usually due to autoimmune-based haemolysis. (2, 4, 5) There is a distinct elevation of LDH and alkaline phosphatase. (7) Hence, the following enzyme constellation can be evaluated as the biochemical triad of hepatitis mononucieosa ... 

Severe overdosage of sodium aurothiopropanol sulfonate (1.1 g daily for 13 days) caused jaundice and skin eruptions. Liver biopsies showed modest centrilobular necrosis and significant bile stasis. Serum hepatic enzyme activities were increased. The patient was treated with dimercaprol and recovered after 2 months, although alkaline phosphatase and gamma-glutamyl-transferase activities remained high for 6 months. 

Hepatic enzyme changes, initially reported as rare with oxamniquine, may in fact be frequent if sought. In one study, there were changes in 79% of patients, with raised alkaline phosphatase in 36% and a raised eosinophil count in 52% (SEDA-13, 837) (6). 

Hepatic Clearance Patients with significant hepatic dysfunction would be expected to have a decreased ability to metabolize or clear drugs. An increase in liver enzymes (aspartate aminotransferase [ASTI, alanine aminotransferase [ALT], and alkaline phosphatase [AlkPhos]) or an increase in bilirubin, prothrombin time and a decrease in serum albumin usually indicates hepatic dysfunction. 

In liver metastases, the serum alkaline phosphatase level shows a better correlation with the extent of liver involvement than those of other liver tests. To differentiate the origin of elevated alkaline phosphatase levels, tests of other liver enzymes may be performed, such as that for 5 -nucleotidase or y-glutamyltransferase. Determination of alkaline phosphatase isoenzymes may provide additional specificity. The liver isoenzyme is thermally more stable than the bone isoenzyme (see Chapter 21 for a more detailed discussion). Other malignancies, such as leuicemia, sarcoma, and lymphoma complicated with hepatic infiltration, may also show elevated ailcaline phosphatase levels. 

Our data support the statement that the heat sensitivity of each enzyme source remains characteristic and independent of the influence of the others in the mixture, and that the resultant heat inactivation is an additive function of the heat-sensitivities of members of the mixture. Bone enzyme from different sources is very consistently heat-sensitive (85-90%), unlike intestinal (50-65%), and liver enzyme (50-75%). However, the heat sensitivity of the LPSAP of normal serum can vary from 33 to 85% and of the non-LPSAP fraction from 50 to 95%. Therefore one cannot determine the identity of the organ sources of serum alkaline phosphatase with a knowledge of only the heat sensitivity and the total alkaline phosphatase. However, by correcting the heat-inactivation of serum by that contributed by intestinal component, one obtains the heat-inactivation of non-intestinal sources of alkaline phosphatase. If this value is 90% or more, the non-intestinal component could be presumed to be of osseous origin if 60% or less, of hepatic origin. 

Hepatic Effects. Workers exposed chronically to 0.01-0.5 mg/m of vanadium dusts had normal serum levels of four enzymes (serum alkaline phosphatase, alanine amino- transferase, aspartate aminotransferase, and lactate dehydrogenase) that are commonly used to detect possible liver damage (Kiviluoto et al. 1981a). 

Chaparral can be found in health food stores as capsules and tablets and is used as an antioxidant and anti-cancer herbal product. Leaves, stems and bark in bulk are also available for brewing tea. However, this product can cause severe hepatotoxicity. Several reports of chaparral-associated hepatitis have been reported. A 45-year-old woman who took 160 mg of chaparral per day for 10 weeks presented with jaundice, anorexia, fatigue, nausea and vomiting. Liver enzymes and other liver function tests showed abnormally high values (ALT 1611 U L- AST 957 U L, alkaline phosphatase 265 U L, GOT 993 U L and bilirubin... 

Often there is no good clinical test available to determine the exact type of hepatic lesion, short of liver biopsy. There are certain patterns of enzyme elevation that have been identified and can be helpful (Table 38-3). ° The specificity of any serum enzyme depends on the distribution of that enzyme in the body. Alkaline phosphatase is found in the bile duct epithelium, bone, and intestinal and kidney cells. 5-Nucleotidase is more specific for hepatic disease than alkaline phosphatase, because most of the body s store of 5 -nucleotidase is in the liver. Glutamate dehydrogenase is a good indicator of centrolobular necrosis because it is found primarily in centrolobular mitochondria. Most hepatic cells have extremely high concentrations of transaminases. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are commonly measured. Because of their high concentrations and easy liberation from the hepato-cyte cytoplasm, AST and ALT are very sensitive indicators of necrotic lesions within the liver. After an acute hepatic lesion is established, it may take weeks for these concentrations to return to normal. ... 

Occupational Exposure. Hepatic effects have been investigated in a number of epidemiology studies and clinical surveys of PCB-exposed workers. Increased serum levels of liver-related enzymes, particularly gamma-glutamyl transpepfidase (GTP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), and/or lactate dehydrogenase (LDH), were reported... 

TNAP is expressed in human hepatocytes, and bile acids increase its activity [93] and secretion in the bile [94]. TNAP in rat hepatocytes is predominantly localized in the bile canalicular domain of the plasma membrane [95, 96], but can be addressed to the baso-lateral membrane in the presence of high levels of bile acid [97]. In contrast, mouse hepatocytes do not express TNAP [98]. In humans, liver TNAP may be expressed both at the sinusoidal and biliary pole of the hepatocyte. This explains why a significant proportion of TNAP activity in the circulation of healthy individuals originates from the liver. TNAP serum levels are of major clinical relevance as a marker of cholestasis. AP levels increase due to retrograde reflux of biliary alkaline phosphatase, enhanced hepatic synthesis and enzyme release into the serum, and induction of the intestinal alkaline phosphatase form [94, 99, 100]. 

M16. Molander, D. W., Graver, L. F., and Packs, G. T., Liver enzymes, serum glutamic oxalacetic transminase, cholinesterase and alkaline phosphatase in primary and metastatic hepatic neoplasia. Acta Unio Int. Cancrum 16, 1478-1481 (1960). 

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