Cirrhosis alkaline phosphatase

Alkaline phosphatase levels and GGT are elevated in plasma with obstructive disorders that disrupt the flow of bile from hepatocytes to the bile ducts or from the biliary tree to the intestines in condition such as primary biliary cirrhosis, sclerosing cholangitis, drug-induced cholestasis, gallstone disease, and autoimmune cholestatic liver disease. 

In addition to the classical symptoms of zinc deficiency mentioned above, the following unusual conditions have been reported liver and spleen enlargement, abnormal dark adaptation and abnormalities of taste. Several laboratory procedures for diagnosing zinc deficiency are available. Measurement of zinc levels in plasma is useful in certain cases. Levels of zinc in the red cells and hair may be used for assessment of body zinc status. More accurate and useful parameters are neutrophil zinc determination and quantitative assay of alkaline phosphatase activity in neutrophils. Determination of zinc in 24 h urine may help diagnose deficiency if sickle cell disease, chronic renal disease and liver cirrhosis are ruled out. A metabolic balance study may clearly distinguish zinc-deficient subjects. 

Primary bihary cirrhosis May be asymptomatic. Prominent rise in alkaline phosphatase, cholesterol and bilirubin. More common in women. Diagnosis through detection of antimitochondrial antibodies, with biopsy. 

Alkaline phosphatase (ALP) Liver kidney, bone, placenta, intestine, biliary epithelia 30-300 lU/L (higher in children due to increased bone growth) Raised levels may indicate biliary inflammation/ obstruction, malignant infiltration, cirrhosis, bone destruction, Paget s disease... 

Depending on the nature of the chronic liver disease, the biliary tract may or may not be affected, and hence bilirubin and alkaline phosphatase may be normal or raised. For example, a patient with primary biliary cirrhosis (PBC) can have an alkaline phosphatase and bilirubin raised to twice ULN. Where there is biliary involvement there is the potential for reduced fat-soluble vitamin absorption. ITence a raised alkaline phosphatase may have occurred over time owing to decreased vitamin D absorption affecting bone development, rather than being associated with the liver. Likewise, the clotting may be abnormal because of vitamin K deficiency. 

A small historical study evaluated the effect of DMPA on six patients with either chronic active viral hepatitis or primary biliary cirrhosis. The study showed that DMPA actually improved transaminase levels and the metabolic ability of the liver. The investigators suggested that the immune-modifying properties of medroxyprogesterone may make the hormone a therapeutic alternative [2]. There were limitations in that this was a very small, non-randomised study, and therefore it is difficult to make specific recommendations based on the outcome. Another study of the metabolic effects of DMPA in women who had used the method for five years or more suggested that there was a significant rise in plasma insulin, alkaline phosphatase and morning cortisol levels in the DMPA users [31]. 

Felty s syndrome (A.R. Felty, 1924) is a special form of seropositive polyarthritis. It leads to considerable changes in the articular structures. Characteristic findings include splenomegaly, leucopenia, lymphadenopathy and skin pigmentation. Men are mainly affected. The liver is involved in about 70% of patients. Transaminases and y-GT values are moderately elevated, and there is an occasional rise in alkaline phosphatase. Lymphocytic infiltrates of the sinusoids, proliferation of Kupffer cells and periportal fibrosis are detectable histologically. Nodular regenerative hyperplasia can develop, which may subsequently cause portal hypertension and macronodular cirrhosis. (71, 95, 104)... 

Using the Bodansky (B18, 52) procedure with 8-glycerophosphate as substrate, Woodard (W8) was unable to obtain such elevations. She determined the serum acid phosphatase activities in 83 females and 342 males, or a total of 425 patients with miscellaneous diseases. Of these, 61 had various types of infectious or metabolic disorders, including 11 cases of inflammatory disease of bone and 12 cases of hepatic cirrhosis. The remainder had some type of neoplastic disease and about one-third had metastases to bone from cancer of various primary sites. There were 15 cases of osteogenic sarcoma and 32 cases of osteitis deformans. All these cases, whether their serum alkaline phosphatase activities were elevated or not, had serum acid phosphatase values that were essentially within the normal range, 0.06-0.89 Bodansky unit for females and 0.11-0.88 unit for males. In contrast to the Gutman method (GIO, G14), there-... 

Fatal liver damage was observed particularly in the UK and tended to occur in elderly subjects. The complication initially presented as jaundice or raised liver enzymes (including alkaline phosphatase). Surprisingly, biochemical and histological liver changes were not consistent with major hepatocellular damage. There were three reports of primary biliary cirrhosis, but a causal relation was not proven (SEDA-12, 84). 

A 49-year-old man with alcoholic cirrhosis developed jaundice, fatigue, and choluria after he started to take celecoxib 200 mg/day for musculoskeletal pain (9). There were increases in transaminases, alkaline phosphatase, and bilirubin (to 547 pmol/l). Liver biopsy showed cirrhosis and marked hepatocellular cholestasis. On withdrawal of celecoxib the bilirubin began to fall very slowly 1 year later he was well, with a total bilirubin concentration of 44 pmol/l. 

Water retention due to sodium chloride (salt) is a common manifestation that leads to weight gain. Edema is also found in patients with cardiac heart failure, renal insufficiency, liver cirrhosis, and hypo-proteinemia. When large doses are used to treat neoplastic diseases, compounds with 17-alkyl substitutions can cause cholestatic hepatitis at high doses, jaundice is the most common clinical feature with accumulation of bile in the bile capillaries. Jaundice usually develops after 2-5 months of therapy. It can be detected by increases in plasma aspartate aminotransferase and alkaline phosphatase. 

In Ghosh and Nath s experiments with paper electrophoresis (barbitone buffer, pH 8.6), rachitic serum showed an alkaline phosphatase mobility close to the mobility of jS-globulin (Nil). Sera from infective hepatitis and obstructive biliary cirrhosis, however, showed maximum alkaline phosphatase activity in the 2-globulin zone (G5). 

Fig. 23. Demonstration of heterogeneity of L-phenylalanine-sensitive serum alkaline phosphatase in a patient with alcoholic cirrhosis [according to Kreisher et al. (K25)].

The biochemical fractions of the serum alkaline phosphatase in cirrhosis are listed in Table 13 according to blood types A and 0. It may be advantageous to compare the various moieties in these patients with the data on normal subjects of corresponding blood type (Table 10). In some cases (4, 5, 14) the elevation is proportionate in the LPSAP and non-LPSAP moieties, whereas in others (1, 2, 3, 9, 10, 12, 13, 15) there is a disproportionate elevation in the LPSAP fraction. Subject 7 exhibits the largest contribution of LPSAP (60%). There appears to be no similarity of the heat sensitivities of LPSAP and non-LPSAP in subjects 4, 5, 7, 14, and 15 with total LPSAP hyperphosphatasemia. In fact, the relatively high heat inactivation of sera 5, 6, 7, and 12 would register negatively for liver in a heat-inactivation test of total alkaline phosphatase (P19). 

The application of the heat-sensitive measurement by Posen et al. (P19, P20) has been restricted to sera of patients with uncomplicated liver or bone disease. Here, sera with high inactivation of alkaline phosphatase are interpreted as bone and those that are relatively heat-stable as liver. Particularly disturbing to us were sera from patients with cirrhosis of the liver (patients 5, 6, and 12, Table 13) exhibiting heat sensitivity of non-LPSAP in the bone range. The measurement of heat sensitivity of serum alkaline phosphatase alone cannot be used for the certain identification of liver or bone sources or their mixtures. 

F14. Fishman, W. H., Inglis, N. I., and Krant, M. J., Serum alkaline phosphatase of intestinal origin in patients with cancer and with cirrhosis of the liver. Clin. Chim. Acta 12, 298-303 (1965). 

The liver can be involved in CF. Biliary cirrhosis secondary to bile duct obstruction occurs in as many as 18% of patients, whereas fatty infiltration occurs in about 30% of patients in a pattern unrelated to nutritional status. Bile ducts may be obstructed by inspissated mucus, which may lead to focal or multilobar cirrhosis. Such hepatic involvement can occur at any age but is more common with advancing age and can lead to portal hypertension, esophageal varices, and hypersplenism. The most common laboratory abnormality associated with hepatic involvement is elevated serum hepatic isoenzymes (gamma-glutamyltranspeptidase, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase)." ... 

Vitamin A intoxication may result in hepatomegaly (S70) or hepatic cirrhosis (R34). While hyperphosphatasemia accompanies the more severe degrees of hepatic damage, cases with normal serum alkaline phosphatase values in the presence of hepatomegaly have been described (S70). 

Fig. 10. Serum alkaline phosphatase values (King-Armstrong units/deciliter) in 49 patients with documented bile duct obstruction (solid circles) and in 49 patients with hepatic cirrhosis or hepatitis (open circles). Note the si ficant overlap between the groups. Note also that the highest value in biliary obstruction was Iras than ten times the upper limit of normal. From Hill and Zieve (H14) with permission.

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