The Vasculitides

© Dirk Biddle

1.8.10 Electrolytes and Metabolites

1.8.10.1 Enzymes

Aspartate Transaminase (AST) /Serum glutamic pyruvic transaminase (SGOT), Alanine Transaminase (ALT)/Serum glutamic oxaloacetic transaminase (SGPT), Gamma Glutamytransferase (GGT), and Alkaline Phosphatase (AP) are proteins called enzymes which help all the chemical activities within cells to take place. Injury to cells cause the release of these enzymes into the blood. They are found in muscles, the liver and the heart. Damage from alcohol and a number of diseases are reflected in high values.

i) Alkaline Phosphatase (AP) is an enzyme related to blood found primarily in bones and the liver. Smaller amounts are in the kidneys, heart, and muscles. Elevations in alkaline phosphate may indicate liver or bone disease. However, expected values are higher for those who are growing (children and pregnant women) or when damage to bones or liver has occurred, or with gallstones. Low values are probably not significant.

ii) Gamma Glutamyl Transferase (GGT, Gamma-GT, GGTP) is an enzyme found mainly in the liver and is sensitive to changes in liver function. GGT participates in the transfer of amino acids across the cellular membrane and in glutathione metabolism. High concentrations are found in the liver, bile ducts, and the kidney. It is the earliest liver function to become abnormal. This test is used to detect diseases of the liver, bile ducts, and kidney; and to differentiate liver or bile duct (hepatobiliary) disorders from bone disease.

Low levels are normally present in the blood. Elevations can occur in all types of liver disease, and with the consumption of alcohol and some medications. GGT is the most sensitive liver enzyme in detecting bile duct problems. However, it can be elevated even without bile duct problems if someone is overweight or has excess fat in the liver.

Unlike alkaline phosphatase (AP) GGT is not elevated with bone growth or damage. Thus GGT is measured in combination with other tests. In particular, AP is increased in hepatobiliary disease and bone disease. GGT is elevated in hepatobiliary disease, but not in bone disease. So, a patient with an elevated AP and a normal GGT probably has bone disease, not hepatobiliary disease (1).

iii) Aspartate Transaminase (AST – aspartate aminotransferase) / Serum Glutamic Oxaloacetic Transaminase (SGOT) is an enzyme found normally in heart and liver cells. When liver or heart muscle cells are injured, they release AST/SGOT into the blood. AST/SGOT levels are thus elevated in the blood with liver damage (for example, from viral hepatitis) or with an insult to the heart (for example, from a heart attack). AST/SGOT also may be released from red blood cells if those cells are damaged when blood is being drawn. Some medications can also raise AST/SGOT levels (see below).

iv) Alanine Transaminase (ALT - alanine aminotransferase)/ Serum Glutamic Pyruvic Transaminase (SGPT), normally found largely in the liver. This is not to say that it is exclusively located in liver but that is where it is most concentrated. It is released into the bloodstream as the result of liver injury. It therefore serves as a fairly specific indicator of liver status.

NOTE: AST/SGOT and ALT/SGPT are sensitive indicators of liver damage from different types of disease. It must however be emphasized that higher-than-normal levels of these liver enzymes should not be automatically equated with liver disease. They may mean liver problems or they may not. The interpretation of elevated AST/SGOT and ALT/SGPT levels depends upon the whole clinical picture and so it is best done by doctors experienced in evaluating liver disease.

Further, the precise levels of these enzymes do not correlate well with the extent of liver damage or the prognosis (outlook). Thus, the exact levels of AST/SGOT and ALT/SGPT cannot be used to determine the degree of liver disease or predict the future. For example, patients with acute viral hepatitis A may develop very high AST/SGOT and ALT/SGPT levels (sometimes in the thousands of units/litre range). But most patients with acute viral hepatitis A, recover fully without residual liver disease. For a contrasting example, patients with chronic hepatitis C infection typically have only a little elevation in their AST/SGOT and ALT/SGPT levels. Some of these patients may have quietly developed chronic liver disease such as chronic hepatitis and cirrhosis (advanced scarring of the liver) (2).

The most common cause of mild to moderate elevations of these liver enzymes is fatty liver. In the United States, the most frequent cause of fatty liver is alcohol abuse. Other causes of fatty liver can include diabetes mellitus and obesity. Chronic hepatitis C is also becoming an important cause of mild to moderate liver enzyme elevations.

A host of medications can cause abnormal liver enzymes levels. These include:

Pain relief medications such as aspirin, acetaminophen (Tylenol), ibuprofen (Advil, Motrin), neproxen (Narosyn), diclofenac (Voltaren), and phenybutazone (Butazolidine),

Anti-seizure medications such as phenytoin (Dilantin), valproic acid, carbamazepine (Tegretol), and Phenobarbital, Antibiotics such as the tetracyclines, sulfonamides, isoniazid (INH), sulfamethoxazole, trimethoprim, nitrofurantoin, etc., Cholesterol lowering drugs such as the "statins" (Mevacor, Pravachol, Lipitor, etc.) and niacin, Cardiovascular drugs such as amiodarone (Cordarone), hydralazine, quinidine, etc., and Trycyclic anti-depressants. With drug-induced liver enzyme abnormalities, the enzymes usually normalize weeks to months after stopping the medications (2).

iv) LDH is an enzyme present in all the cells in the body. Anything which damages cells, including blood drawing itself, will raise amounts in the blood. If blood is not processed promptly and properly, high levels may occur. If all values except LDH are within expected ranges, it is probably a processing error and does not require further evaluation.

v) Bilirubin (see also 1.8.9 Waste products) is a pigment removed from the blood by the liver. Low values are of no concern. If slightly elevated above the expected ranges, but if all other enzymes (AST/SGOT, ALT/SGPT, GGT, LDH) are within expected values, it is probably a condition known as Gilbert’s syndrome and is not significant.

vi) Creatine phosphokinase (CPK) is found predominantly in the heart, brain, and skeletal muscle. When the total CPK level is substantially elevated, it usually indicates injury or stress to one or more of these areas and is thus very useful for diagnosing diseases of the heart and skeletal muscle. This enzyme is the first to be elevated after a heart attack (3 to 4 hours). If CPK is high in the absence of heart muscle injury, this is a strong indication of skeletal muscle disease.

When a muscle is damaged, CPK leaks into the bloodstream. Determining which isoenzyme (specific form of CPK) is elevated will help determine which tissue has been damaged. This test may be used to: Diagnose heart attack, Evaluate cause of chest pain, Determine the extent of muscle damage caused by drugs, trauma or immobility, Detect early dermatomyositis and polymyositis, Distinguish malignant hyperthermia from a postoperative infection, and help discover carriers of muscular dystrophy (Duchenne).

Repeated checks of CPK levels may be performed. The pattern and timing of a rise or fall in CPK levels can be diagnostically significant, particularly if a heart attack is suspected.

Higher than normal total CPK levels may be seen with conditions such as:

Heart attack, Myocarditis (inflammation of the heart muscle), Central nervous system trauma or stroke, Convulsions, Delirium tremens, Dermatomyositis or polymyositis, Electric shock, Muscular dystrophies, and Pulmonary infarction (lung tissue death).

Additional conditions that may give positive test results include Hypothyroidism, Pericarditis following a heart attack and Rhabdomyolysis (3).

Other tests should be conducted to determine the exact location of muscle damage.

Factors that may affect test results include cardiac catheterization, intramuscular injections, trauma to muscles, recent surgery, and vigorous and prolonged exercise.

Drugs that can increase CPK measurements include amphotericin B, ampicillin, some anaesthetics, anticoagulants, aspirin, clofibrate, dexamethasone, furosemide, morphine, alcohol, and cocaine (3).

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1 http://health.allrefer.com/health/gamma-glutamyl-transpeptidase-info.html

2 http://www.medicinenet.com/liver_blood_tests/page2.htm#3whatare

3 http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm

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