Assalamualaikum. In the Name of Allah the Most Beneficent the Most Merciful
Blood tests for LIVER
Liver function tests
Serum albumin
This is a marker of synthetic function and is a valuable guide to the severity of chronic liver disease. A falling serum albumin in liver disease is a bad prognostic sigh. In acute liver disease initial levels may be normal.
Prothrombin time (PT)
This is also a marker of synthetic function. Because of its short half-life, it is a sensitive indicator of both acute and chronic liver disease. Vitamin K deficiency should be excluded as the cause of a prolonged PT by giving an intravenous bolus (10mg) of vitamin K. Vitamin K deficiency commonly occurs in biliary obstruction, as the low intestinal concentration of bile salts results in poor absorption of vitamin K.
Prothrombin times vary in different laboratories depending upon the thromboplastin used in the essay. The International Normalized Ratio (INR) is therefore used in many countries but does not eliminate variation across laboratories.
Liver biochemistry
Bilirubin
In the serum, bilirubin is normally almost all unconjugated. In liver disease, increased serum bilirubin is usually accompanied by other abnormalities in liver biochemistry. Determination of whether the bilirubin is conjugated or unconjugated is only necessary in congenital disorders of bilirubin metabolism or to exclude hemolysis.
Aminotransferases
These enzymes (often referred to as transaminases) are present in hepatocytes and leak into the blood with liver cell damage. Two enzymes are measured:
- Aspartate aminotransferase (AST) is primarily a mitochondrial enzyme (80%; 20% in cytoplasm) and is also present in heart, muscle, kidney and brain. High levels are seen in hepatic necrosis, myocardial infarction, muscle injury and congestive cardiac failure.
- Alanine aminotransferase (ALT) is a cytosol enzyme, more specific to the liver so that a rise only occurs with liver disease.
Alkaline phosphatase (ALP)
This is present in the canalicular and sinusoidal membranes of the liver, but is also present in many other tissues, such as bone, intestine, and placenta. If necessary, its origin can be determined by electrophoretic separation of isoenzymes or bone-specific monoclonal antibodies. Alternatively, if there is also an abnormality of, for example, the γ-GT, the ALP can be presumed to come from the liver (e.g. metastases) and cirrhosis, frequently in the absence of jaundice. The highest serum levels due to liver disease (>1000 IU/L) are seen with hepatic metastases and primary biliary cirrhosis.
γ-Glutamyl transpeptidate
This is a microsomal enzyme that is present in many tissues as well as the liver. Its activity can be induced by such drugs as phenytoin and by alcohol. If the ALP is normal, a raised serum γ-GT is a good guide to alcohol intake and can be used as screening test. Mild elevation of the γ-GT is common even with a small alcohol consumption and does not necessarily indicate liver disease if the other liver biochemical tests are normal. In cholestasis the γ-GT rises in parallel with the ALP as it has a similar pathway of excretion. This is also true for the 5-nucleotidase, another microsomal enzyme that can be measured in blood.
Total proteins
This measurement, in itself, is of little value. Serum albumin is discussed above. The globulin fraction consists of many proteins that can be separated on electrophoresis. A raised globulin fraction, seen in liver disease, is usually due to increased circulating immunoglobulins and is polyclonal.
Viral markers
Viruses are a major cause of liver disease. Virological studies have a key role in diagnosis; markers are available for most common viruses that cause hepatitis.
Additional blood investigations
Hematological
A full blood count is always performed. Anemia may be present. The red blood cells are often macrocytic and can have abnormal shapes – target cells and spur cells – owing to membrane abnormalities. Vitamin B 12 levels are normal or high, while folate levels are often low owing to poor dietary intake. Other changes are caused by the following:
- Bleeding produces a hypochromic, microcytic picture.
- Alcohol causes macrocytosis, sometimes with leucopenia and thrombocytopenia.
- Hypersplenism results in pancytopenia.
- Cholestasis can often produce abnormal-shaped cells and also deficiency of vitamin K.
- Hemolysis accompanies acute liver failure and jaundice.
- Aplastic anemia is present in up to 2% of patients with acute viral hepatitis.
- A raised serum ferritin with transferrin saturation (>60%) is seen in hereditary hemochromatosis.
Biochemical
- a1-Antitrypsin. A deficiency of this enzyme can produce cirrhosis.
- α-Fetoprotein. This is normally produced by the fetal liver. Its appearance in increasing and high concentrations in the adult indicates hepatocellular carcinoma. Increased concentrations in pregnancy in the blood and amniotic fluid suggest neural tube defects of the fetus. Blood levels are also slightly raised with regenerative liver tissues in patients with hepatitis, chronic liver disease and also in teratomas.
- Serum and urinary copper and serum caeruloplasmin – for Wilson’s disease.
Immunological tests
Serum immunoglobulins
Increased γ-globulins are thought to be due to reduced phagocytosis by sinusoidal and Kupffer cells of the antigens absorbed from the gut. These antigens then stimulate antibody production in the spleen, lymph nodes and lymphoid and plasma cell infiltrate in the portal tracts. In primary biliary cirrhosis, the predominant serum immunoglobulin that is raised is IgM, while in autoimmune hepatitis it is IgG.
Serum autoantibodies
- Anti-mitochondrial antibody (AMA) is found in the serum in over 95% of patients with primary biliary cirrhosis. Many different AMA subtypes have been described, depending on their antigen specificity. AMA is demonstrated by an immunofluorescent technique and is neither organ- nor species-specific. Some subtypes are occasionally found in autoimmune hepatitis and other autoimmune diseases.
- Nucleic, smooth muscle (actin), liver/kidney microsomal antibodies can be found in the serum in high titre in patients with autoimmune hepatitis. These antibodies can be found in the serum in other autoimmune conditions and other liver diseases.
- Anti-nuclear cytoplasmic antibodies (ANCA) are present in primarily sclerosing cholangitis.
Markers of liver fibrosis
Fibrosis plays a key role in the outcome of certain chronic liver diseases, particularly non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C disease. Blood tests are being used to decrease the reliance on liver biopsy as the definitive way of detecting fibrosis.
Fibrotest/fibrosure tests measure α2-macroglobulin, α2-haptoglobulin, γ-globulin, apoprotein A1, γ-GT and total bilirubin. These results are formulated to determine a fibrosis index. The index is sensitive and specific (>90%) for the absence of fibrosis, and has 80% sensitivity and specificity for severe fibrosis.
Markers of matrix deposition include procollagen I and III peptide and Type IV collanen. Markers of matrix degradation, e.g. matrix metalloproteinases (MMP) 2, 3, 9, and tissue inhibitors of mettaloproteinases (TIMPS), e.g. TIMP1 and 2 all are being used as markers of fibrosis.
Genetic analysis
These tests are preformed routinely for hemochromatosis (HFE gene) and for α1-antitrypsin deficiency. Markers are also available for Wilson’s disease.
Urine tests
Dipstick tests are available for bilirubin and urobilinogen. Bilirubinuria is due to the presence of conjugated (soluble) bilirubin. It is found in the jaundiced patient with hepatobiliary disease; its absence implies that the jaundice is due to increased unconjugated bilirubin. Urobilinogen in the urine is, in pracetisce, of little value but suggests hemolysis or hepatic dysfunction of any cause.
copied bulat bulat from: Kumar&Clarks, pg 324-325
No comments:
Post a Comment