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Liver Diseases

Question: What are the abnormal enzymatic characteristics you would see in liver diseases and heart diseases? What are the abnormal enzymatic characteristics you would see in liver diseases and heart diseases?

Answer: An enzyme test is a blood test that measures certain enzyme levels to assess how well the body’s systems are functioning and whether there has been any tissue damage. Liver function tests (LFTs or LFs) include liver enzymes to give information about the state of a patient's liver. The list of major enzymes involved are given below: Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Alkaline phosphatase Gamma-glutamyltranspeptidase (GGT) 5' nucleotidase (5'NTD) Alanine transaminase (ALT) Alanine transaminase (ALT), also called Serum Glutamic Pyruvic Transaminase (SGPT) or Alanine aminotransferrase (ALAT) is an enzyme present in hepatocytes (liver cells). When a cell is damaged, it leaks this enzyme into the blood, where it is measured. ALT rises dramatically in acute liver damage, such as viral hepatitis or paracetamol (acetaminophen) overdose. Elevations are often measured in multiples of the upper limit of normal (ULN). The reference range is 15-45 U/L in most laboratories. Aspartate transaminase (AST) Aspartate transaminase (AST) also called Serum Glutamic Oxaloacetic Transaminase (SGOT) or aspartate aminotransferase (ASAT) is similar to ALT in that it is another enzyme associated with liver parenchymal cells. It is raised in acute liver damage. It is also present in red cells, and cardiac and skeletal muscle. The ratio of AST:ALT is useful in differentiating between causes of acute hepatitis. Alkaline phosphatase (ALP) Alkaline phosphatase (ALP) is an enzyme in the cells lining the biliary ducts of the liver. ALP levels in plasma will rise with large bile duct obstruction, intrahepatic cholestasis or infiltrative diseases of the liver. ALP is also present in bone and placental tissue, so it is higher in growing children (as their bones are being remodelled). The reference range is usually 30-120 U/L. Gamma glutamyl transpeptidase (GGT) Although reasonably specific to the liver and a more sensitive marker for cholestatic damage than ALP, Gamma glutamyl transpeptidase (GGT) may be elevated with even minor, sub-clinical levels of liver dysfunction. It can also be helpful in identifying the cause of an isolated elevation in ALP. GGT is raised in alcohol toxicity (acute and chronic). 5' nucleotidase (5'NTD) 5'NTD is another test specific for cholestasis or damage to the intra or extrahepatic biliary system, and in some laboratories, is used as a substitute for GGT for ascertaining whether an elevated ALP is of biliary or extra-biliary origin. Cardiac enzyme tests are used in making the diagnosis of a heart attack and determining the extent to which the heart muscle was damaged. Less frequently, cardiac enzyme tests can also help diagnose a variety of other cardiovascular conditions, including coronary artery disease, heart failure and alcoholic cardiomyopathy. The two most common cardiac enzyme tests performed are: Creatine kinase (CK) Cardiac troponin Lactate dehydrogenase (LDH) Alternatively, another enzyme, aspartate aminotransferase (AST), is sometimes measured to detect heart damage. However, AST is a liver enzyme and is more commonly measured as part of a standard liver function test to diagnose and monitor liver disease. This test is rarely performed in connection with heart attack. Creatine kinase Also known as creatine phosphokinase (CPK), creatine kinase (CK) is a cardiac enzyme that helps convert creatine to creatinine, a reaction that is necessary for metabolism and energy production. Creatine kinase is made up of three important isoenzymes: CK-BB (CK1). Exists primarily in the brain. CK-BB can be an important indicator of tissue damage in the brain from stroke, trauma or other causes. CK-MB (CK2). The primary indicator used to diagnose a heart attack because it exists in the highest amount in the heart. If CK-MB makes up more than 5 percent of a total CK level, a heart attack is suspected. CK-MB rarely rises following chest pain caused by angina, pulmonary embolism or heart failure, making it a valuable tool for determining whether a heart attack is the cause of chest pain. CK-MB levels typically increase to above normal levels about six hours after a person has had a heart attack. Furthermore, if one part of CK-MB (CK-MB2) is greater than another part (CK-MB1) by a ratio of 1.5 or more, then this is another indication that a heart attack has occurred. CK-MB levels can also be used after balloon angioplasty and other catheter-based techniques. Studies have shown an increased risk of sudden cardiac death with higher CK-MB levels after these procedures. CK-MM (CK3). Exists primarily in skeletal muscle. Creatine kinase tests may measure total CK levels or may break out the individual levels of CK-BB, CK-MB and CK-MM. Normal results are as follows: Total creatine kinase level (CK total). Normal levels are 25 to 130 micrograms per liter for men and 10 to 150 micrograms per liter for women. CK levels may be much higher in very muscular people, and infants up to 1 year may have levels up to four times the normal adult level. According to the American College of Cardiology (ACC), total CK levels should not be used in the diagnosis of heart attack. Instead, the College recommends that physicians rely on the more sensitive CK-MB levels, which are specific to the heart. CK-BB. Unless tissue damage in the brain has occurred, CK-BB levels will be undetectable. CK-MB. Normal range is from undetectable to 7 micrograms per liter. CK-MM. Normal range is from 5 to 70 micrograms per liter. Cardiac troponin There are two types of cardiac troponin in cardiac muscle – Troponin T (cTNT) and Troponin I (cTNI). These proteins control the interactions of two other substances (actin and myosin) that cause the heart muscle to contract or squeeze. Normal levels of cardiac troponin in the blood are very low, but they rise sharply and quickly in response to a heart muscle injury. Unlike creatine kinase (CK), cardiac troponin will also rise in response to angina, which is one reason the two tests are often performed together. Cardiac troponin is more sensitive to damage than CK and is therefore valuable at detecting mild heart attacks and early detection of other heart problems. Troponin T and I levels have also been used to help predict a patient’s heart attack risk because of their sensitivity and the fact that elevated levels are specific to a heart injury. Because troponin is filtered by the kidneys, it had been held that troponin level testing was not reliable in patients with renal disease. Recent studies have shown, however, that the test is sensitive enough even when the kidneys are not functioning normally, and the American Heart Association believes that the results of a troponin test could help identify people at a higher risk of a serious cardiovascular problem or death. Normal cardiac troponin levels are as follows: cTNT. Normal range is less than 0.1 nanograms per milliliter. cTNI. Normal range is less than 0.4 nanograms per milliliter. Lactate dehydrogenase Until recently, levels of lactate dehydrogenase (LDH) were used to measure cardiac damage. However, there were certain drawbacks with this approach. LDH is an enzyme that helps convert lactic acid to pyruvic acid. It is present in nearly all body tissues. Because troponin is specific to cardiac muscle, the LDH test has largely been replaced by the troponin test. Currently, the American College of Cardiology (ACC) does not recommend measuring LDH in the diagnosis of heart attack. Heart damage and cardiac enzymes When heart damage occurs, the heart releases enzymes at a predictable pace. Troponin levels begin to rise four to six hours after a heart attack and peak within 10 to 24 hours. Elevated levels can still be detected a week or more after the onset of chest pain. CK-MB levels begin to rise two to three hours after a heart attack and may remain elevated for up to 48 hours after the heart attack. The degree the CK-MB level rises depends on the severity of the heart attack. When these enzyme levels begin to decline, it is a sign that the damaged heart muscle is beginning to heal. Based on this information, physicians can determine from cardiac enzyme tests that: Cardiac enzymes will demonstrate increased activity following heart damage. If subsequent tests show that enzyme activity is decreasing, the heart tissue may be healing. If enzyme activity continues to increase, it is likely that tissue damage is still occurring. If enzyme activity plateaus, begins to decline, then rises again, it is likely a second, follow-up heart attack is occurring Enzyme testing may be done either as part of making an initial diagnosis or to monitor the progress of treatment for a disorder. Some conditions will require a series of regular enzyme tests over time.

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