The liver undertakes a wide range of material metabolic activities The liver contains a large number of enzymes The content of intrahepatic enzymes accounts for 2/3 of the total liver protein Almost all enzymes in the body are present in the liver.
According to their diagnostic significance for hepatobiliary diseases, they are divided into four categories as follows.
1. enzymes of hepatocyte damage: ALT AST LDHChE2. enzymes of cholestasis: ALP AKP GGT5,-NT3. enzymes of liver parenchymal fibrosis: MAO4. enzymes of liver tumors: AKP GGT LDH [enzymes of hepatocyte damage]
1, ALT (1) Most abundant in the liver (2) Most of the ALT activity is present in the soluble cell plasma and is restricted to the cell plasma.
(3) Any damage to hepatocytes, including increased membrane permeability and cell necrosis. Serum enzyme activity will be significantly elevated.
(4) Intrahepatic enzyme activity is about 100 times higher than that of serum, and as little as 1% of hepatocyte necrosis can increase serum enzyme activity by a factor of 1, making it one of the most sensitive indicators of liver function.
(5) Other organs such as skeletal muscle, heart muscle, kidney spleen and brain also contain a certain amount of ALT {significance}
The level of this enzyme is significantly increased in acute hepatitis or acute liver injury such as drug or alcohol intoxication.
Severe hepatitis can appear bile-enzyme separation phenomenon liver but blood can also be significantly elevated.
Heart, skeletal muscle and other tissues this enzyme content is also high, so ALT should be considered when elevated.
2, AST (1) is seen in the mitochondria and cytoplasm of hepatocytes.
(2) also seen in the heart muscle, bone, kidney, brain, etc. (3) AST has two isoenzymes: soluble ASTs distributed in the cytoplasm and ASTm in the mitochondria. In human liver, 81% of the total AST is AST m.
{The significance}
ASTs are significantly elevated in acute hepatitis and may also be elevated in biliary tract disease.
Serum AST s and AST m activity is significantly elevated in acute and chronic hepatitis and active liver disease, and AST m disappears more rapidly than ASTs during the recovery period.
The persistent elevation of ASTm after acute hepatitis suggests chronic prolonged disease.
{The clinical significance of analyzing both ALT and AST together}
(1) The most significant increase in transaminases is seen in cases of poisoning, blood loss, and oxygen deprivation, often more than 20 times normal and up to 10,000u/L.
(2) Acute viral hepatitis is the second highest, usually 300-3000u/L (3) Chronic viral hepatitis and autoimmune hepatitis are within 20 times; among them, chronic hepatitis C often shows continuous mild elevation (within 5 times), and chronic hepatitis B is mostly recurrent and fluctuating elevation.
(4) Alcoholic hepatitis generally has a mild to moderate increase of 100-500u/L, and AST is higher than ALT.
(5) Normal or mildly increased in patients with cirrhosis, generally 2-4 times the normal value.
(6) Other conditions, such as fatty liver, may also show an increase in ALT level of up to 3 times.
{The significance of the AST/ALT ratio in differential diagnosis}
(1) AST/ALT <1 in case of hepatocellular damage.
(2) AST/ALT>1 is common in cirrhosis of various causes; in chronic viral hepatitis, it often indicates fibrous tissue hyperplasia or progression of cirrhosis; in late acute hepatitis, it indicates a tendency to severe hepatitis, and if >2, the prognosis is poor.
(3) AST/ALT >2 and AST level within 300 often suggests alcoholic liver disease; other systemic diseases, myocardial damage, etc. may also appear AST/ALT large rain 1 or 2 (4) AST/ALT >3 and AST greater than 500 suggests circulatory disorders such as left heart failure, or malignant tumors of the liver.
Decay of {transaminases in the circulation}
1. The half-life of aminotransferases is very short. 17 hours for AST and 47 hours for ALT.
2. Their serum levels can reflect the state of liver damage occurring every hour, or at least every day.
If transient liver damage occurs, such as poisoning or shock, AST levels will drop by half each day.
In acute hepatitis, a rise in transaminases for several days in a row suggests greater liver damage and more necrosis.
If the decrease in transaminases for several days suggests reduced liver damage and decreased AST and ALT activity over the past 24 hours, it may be an early sign of recovery, or it may be a sign of extensive hepatic necrosis with only small clusters of hepatocytes remaining, suggesting a poor prognosis.
In biliary obstruction, transaminases may be mildly elevated, and in acute obstruction they may be significantly elevated, greater than 300 u/L. Even if the obstruction is not lifted, the bee value will quickly decrease within 24-48 hours.
{Other factors causing elevated transaminases}
Asthmatic states; heart failure; acute myocardial infarction; ulcer disease, acute pancreatitis; obesity; diabetes mellitus; alcoholism; blood disorders; and when receiving drugs such as para-aminosalicylic acid and erythromycin can be elevated.
In patients on long-term hemodialysis, transaminase levels may decrease due to loss of serum enzymes and pyridoxine phosphate deficiency.
AST decreases in uremia and increases after hemodialysis.
Some patients with chronic liver disease have antibodies to AST in their serum, which reduces AST activity.
Note that changes in ALT levels do not distinguish the exact degree of liver damage, i.e., they do not determine whether the cellular damage is due to increased cell membrane permeability or cellular necrosis. When hepatocyte membrane permeability is increased for various reasons, an increase in serum levels can occur e.g. in acute viral hepatitis, hepatocytes appear as edema without extensive necrosis.
In severe hepatitis, it shows a decrease in serum aminotransferase along with an increase in bilirubin and prolonged prothrombin time, suggesting a poor prognosis.
3. Lactate dehydrogenase (LDH) is significantly elevated in the presence of hepatocyte necrosis, but is poorly specific. It can be significantly elevated in hematogenous hepatitis, viral hepatitis, malignant tumors, especially when the liver is involved.
[Enzymatic markers of cholestasis]
1. Alkaline phosphatase (AKP) AKP is a group of enzymes that hydrolyze phosphate in an alkaline environment.
It is widely present in various tissues, especially in intestinal epithelium, bone, liver, and placental acute leukocytes.
AKP in normal human serum mainly comes from the bones and liver and is excreted via the biliary tract.
The elevation of AKP in liver disease is due to increased synthesis and release, not just a decrease in biliary excretion capacity.
Caution.
Because elevation of serum AKP requires enzyme synthesis, it does not cause elevation of AKP during the first 1-2 days of acute biliary obstruction.
In addition, because the half-life of AKP is approximately 1 week, AKP can persist for days or weeks after biliary obstruction is lifted.
Clinical significance Physiological elevations: bone growth, pregnancy, growth, post-fat meal, etc. Pathological elevations.
(1) Elevations of up to 3-fold lack specificity and are seen in all types of liver disease.
(2) Moderate increases are seen in hepatocellular jaundice.
(3) Significantly elevated in biliary stasis, especially in extrahepatic obstructive jaundice due to tumors and stones. Parallel to the degree of obstruction.
(4) It is invariably elevated in intrahepatic bile duct obstruction.
(5) In biliary stasis, bile acids induce increased hepatocyte synthesis and reflux into the blood, and giant molecules of AKP, complexes of AKP and abnormal lipoprotein-x, or fragments of hepatocyte membranes may appear in the serum.
Significant elevation of serum AKP can be seen in patients with primary or secondary tumors of bone and liver, intrahepatic granulomatous lesions and hepatic tuberculosis.
Primary hepatocellular carcinoma should be suspected in patients with cirrhosis if AKP is more than 3 times the normal value.
Note that elevated serum AKP with normal bilirubin can be seen in infiltrative or occupational lesions of the liver. (due to tumor compression of only the local intrahepatic bile ducts). Such as amyloidosis, abscess, leukemia or sarcoidosis.
AKP reduction: hypothyroidism, anemia, congenital hypophosphatemia zinc deficiency, etc.
2. Serum glutamyl transpeptidase is a peptide transferase that catalyzes the transfer of glutathione or other glutamyl-containing moieties to suitable receptors.
It has a wide distribution, with the highest activity in the epithelial cells of the brush border of the proximal tubule of the kidney and the intrahepatic bile duct. The distribution in bone is very low. This can be used to identify damage to the hepatobiliary and skeletal systems.
Clinical significance This enzyme is used for the diagnosis of liver disease with high sensitivity and poor specificity. In addition to hepatobiliary disease, pancreatic, diabetes, obesity, excessive alcohol intake, and drugs that affect enzyme production can elevate serum GGT.
(1) Cholestasis of all causes is the most sensitive serum enzyme and is somewhat parallel to the extent and progression of the disease. Damage to the small bile ducts and capillary bile ducts of any cause, as well as obstruction of the bile ducts within and outside the liver, significantly increases GGT.
(2) Serum GGT correlates with AKP in hepatobiliary disease and is the most sensitive indicator of biliary disease.
In acute viral hepatitis, serum GGT is elevated, but the magnitude is lower than that of ALT.
In chronic hepatitis as well as other liver diseases, it is more sensitive than ALT, increases with the change of disease, and helps in the estimation of prognosis.
(3) GGT has the same nature of oncoprotein as AFP, and is significantly increased in primary and secondary hepatocellular carcinoma, and can be greater than 4 times or even 10 times the normal value in hepatoblastoma. For those who do not have clinically high bilirubin but have significantly increased GGT, the possibility of hepatocellular carcinoma should be thought of.
(4) When AKP is elevated due to bone disease and GGT is normal.
(5) Alcoholic liver damage, especially in acute alcoholic liver poisoning, GGT is often significantly elevated and can reach more than 10 times normal.
(6) In acute viral hepatitis, GGT parallels the increase in ALT and AST, which can be up to 5 times normal, and gradually decreases as the disease improves, but more slowly than transaminases (which can last more than 6 weeks after transaminases are normal). In chronic hepatitis, while only presenting with abnormal GGT.
(7) Non-alcoholic fatty liver, often manifesting as mildly elevated GGT.
(8) GGT can be used to judge the efficacy of interferon therapy for viral hepatitis, and is effective in patients with low GGT before treatment.
(9) Others GGT is elevated in pancreatic lesions, myocardial infarction, renal failure, rheumatoid arthritis, diabetes mellitus, and chronic obstructive pulmonary emphysema.
Serum 5,-Nucleotidase (5,-NT) 5,-NT is a phosphodiesterase that specifically catalyzes the hydrolysis of 5,-Nucleotide. It is mainly found in the sinusoidal gap membrane of bile ducts.
Elevated serum 5,-NT is only seen in normal pregnancy or in diseases of the hepatobiliary system. The reason for this may be that 5,-NT can only become soluble and enter the blood in the presence of bile salts.
In metastatic hepatocellular carcinoma, 5,-NT is more sensitive and specific than AKP and GGT and is elevated later than AKP and GGT, but is normal in mild liver disease.
Note that 5,-NT is unstable at room temperature and blood specimens should be separated from serum within 1 hour; hemolysis will elevate its measurement.
Enzymes of hepatic fibrosis Monoamine oxidase (MAO) MAO is involved in the oxidative deamination of various monoamines and is present in the connective tissue of the liver, kidney, brain and various organs.
MAO is found mainly in the mitochondria of cells and to a lesser extent in the cell plasma.
MAO is involved in the synthesis of collagen fibers.
The magnitude of MAO elevation in liver cirrhosis is positively correlated with the degree and extent of fibrosis.
An increase in MAO during acute hepatocellular necrosis and marked hepatitis activity suggests active fibrotic tissue proliferation.
Considerations for clinical analysis of liver enzyme changes (1) Gender: GGT is higher in males than in females (2) Age: LDH is highest at birth and is 7 times higher than in adults. ; ALP is 2-4 times higher in children than in normal adults. ; GGT increases with age after lactation.
(3) Eating: ALP can be increased after meals, especially fatty meals; alcohol and alcoholic beverages can increase GGT levels.
(4) Exercise: ALT, AST and LDH increase after a short period of strenuous exercise, especially ALT, which can reach more than one times the normal value.
(5) Pregnancy: The placenta can secrete ALP, LDH and AST, especially in the second trimester.
(6) Certain drugs: such as isoniazid, chlorpromazine, salicylic acid preparations, etc. can cause an increase in ALT: microsomal enzyme inducers such as phenobarbital, phenytoin sodium, etc. can cause an increase in GGT.
(7) Hemolysis: red blood cells contain ALT, AST and 5,-NT, etc.