Elevated enzymes

There are thousands of enzymes in the cells in human bodies, where they normally act as catalysts for all the chemical reactions that take place in these cells. They are speed up these reactions and without them, these reactions either wouldn't occur or would be too slow for the cells' needs. Beside the fact that every organ in our body has its own enzymes, many enzymes are also normally present in the blood and can be measured there. It is important to remember that when cells or tissues are damaged by disease or injury, large amounts of these enzymes leak out, causing blood tests to show that enzymes are elevated above normal.  A laboratory report of elevated liver enzymes is common and it doesn't indicate a specific disease. However, it may be due to a liver disorder, even if you don't have any symptoms of liver problems. Liver enzymes help maintain a variety of chemical and metabolic processes that occur in the liver. Normally, only very small amounts of these enzymes are present in your blood.

Why measuring enzymes?

It is important to know that measuring enzymes isn't the final diagnosis - it is only a clue to a possible diagnosis or problem, not a diagnosis in itself. Elevated enzyme level should only prompt a physician to look further into the areas of the body which may be leaking enzymes into the blood.

Two enzymes often measured on routine tests are known as:

1. ALT (alanine transaminase) - ALT is found in the liver, heart, muscles and kidneys. It is also called as SGPT (serum glutamic-pyruvic transaminase)
2. AST (aspartate transaminase) - AST is in the liver, heart, muscles, kidneys, brain, pancreas, spleen and lungs. It is also called SGOT (serum glutamic-oxaloacetic transaminase)

We can see that two organs that are primary involved in elevation of enzymes are liver and muscles. The liver is an important internal organ because it performs many functions. It helps detoxify the many toxins in the body, makes proteins that are used to help clot the blood and other proteins that help draw fluid into our blood vessels.

Enzymes are capable of processing millions of molecules every second. They are very specific and react with only one or a few types of molecules.

Liver or Muscle?

If a primary disorder hasn't yet been diagnosed, a doctor may be misled into thinking that a damaged liver, not damaged muscles, is the source of the enzyme leak. In the general population, liver damage is more common than muscle damage. Of course, the careful physician will investigate further. There are some diagnostic tools which could help the doctor in differential diagnosis and they are also based on enzymes!

Differential diagnosis

• An enzyme called GGT or gamma-GT (gamma-glutamyltransferase) is found in the liver but not in the muscles.   
• Enzyme CK (creatine kinase), also called CPK (creatine phosphokinase), is only found in the heart, skeletal muscles and brain, but not in the liver.
• The MM form of CK is the type found in skeletal muscles, and it can be specifically measured when a doctor suspects a muscle problem

Liver enzymes

There are exactly 4 separate liver enzymes included on most routine laboratory tests. They are:

• aspartate aminotransferase (AST or SGOT)
• alanine aminotransferase (ALT or SGPT)
• alkaline phosphatase (AP)
• gamma-glutamyl transferase (GGT)

Common causes of elevated liver enzymes include:

• Medications, such as certain nonsteroidal anti-inflammatory drugs, cholesterol-lowering medications, antibiotics and anti-seizure medications
• Drinking too much alcohol
• Obesity
• Diabetes
• Elevated triglycerides
• Infection, such as viral hepatitis and mononucleosis
• Autoimmune disorders of the liver and bile ducts: autoimmune hepatitis (formerly chronic active hepatitis), primary biliary cirrhosis, sclerosing cholangitis
• Metabolic liver disease, such as hemochromatosis and Wilson's disease
• Excessive use of vitamin supplements and certain herbal supplements
• Tumors of the liver or bile ducts

AST and ALT (Transaminases)

These two enzymes, AST and ALT, are jointly known as transaminases. They are associated with inflammation or injury to liver cells. Damage to the liver typically results in a leak of AST and ALT into the bloodstream.
Since AST is found in many other organs besides the liver, including the kidneys, the muscles, and the heart, having a high level of AST does not always indicate that there is a liver problem.
However, high levels of transaminases in the blood don’t always reveal just how badly the liver is inflamed or damaged. The normal ranges for AST and ALT are around 0 to 40 IU/L and 0 to 45 IU/L respectively.
It is important to know that if the liver was damaged years before, by excessive alcohol use for example, the results of a blood test done today may be normal, but a damaged liver may still be present.
 
Males have higher transaminase levels than females. African-American men have higher AST levels compared with Caucasian men. Even the time of day that a blood sample is drawn may influence the level of transaminase elevation. People appear to have higher transaminase levels in the morning and afternoon than in the evening. Most liver diseases are characterized by greater ALT elevations than AST elevations. There are only two exceptions to this rule: both cirrhosis and alcohol abuse are associated with higher AST levels than ALT levels, often in a ratio of approximately 2:1.

Some possible causes of elevated transaminase levels include the following:

• Viral hepatitis
• A fatty liver
• Alcoholic liver disease
• Drug/medication-induced liver disease
• Autoimmune hepatitis
• Herbal toxicity
• Genetic liver diseases
• Liver tumors
• Heart failure
• Strenuous exercise

GGT and AP (Cholestatic Liver Enzymes)

Several researches have came to the same conclusion- high levels of GGT and AP could be possible sign of  blockage of the bile ducts, or of possible injury to, or inflammation of, the bile ducts. This liver injury is known as cholestatic liver injury. Cholestasis can be:

1. Intrahepatic - intrahepatic cholestasis refers to bile duct blockage or injury within the liver. It occurs in people with primary biliary cirrhosis or liver cancer
2. Extrahepatic - this type of cholestasis refers to bile duct blockage or injury occurring outside the liver. It may also occur in people with gallstones.

When a blockage or inflammation of the bile ducts occurs, the GGT and AP can overflow and seep out of the liver and into the bloodstream. GGT is found predominantly in the liver. AP is mainly found in the bones and the liver but can also be found in many other organs, such as the intestines, kidneys, and placenta.  People who smoke cigarettes appear to have higher AP and GGT than nonsmokers for reasons that are still unknown.

Normal levels of AP range from 35 to 115 IU/L and normal levels of GGT range from 3 to 60 IU/L. Some causes of elevated AP and/or GGT include the following:

• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Nonalcoholic fatty liver disease   
• Alcoholic liver disease
• Liver tumors
• Drug-induced liver disease
• Gallstones

Liver function test

What exactly is a liver function test? Blood samples are analyzed for levels of specific enzymes in the blood stream and there are generally 5 – 6 specific things that are checked. Collectively these tests are called a “Liver Function Test”. It is proven that different diseases of the liver will cause Differing types of damage and affect liver function tests accordingly. These tests are helpful, but they do not tell the whole story. They are also useful for monitoring someone with liver disease, but are not always accurate.

A typical liver function test

Each laboratory provides a patient with a“reference range”. This is the average reading that is marked a ‘normal’ reading for the majority of the population. The normal values for liver function tests will vary between men and women, at different times of the day and will change as you get older.

Different laboratories may have slightly Differing reference ranges.

Result Unit Reference

• AP (Alkaline Phosphatase) U/L (30 to 120)
• GGT (Gamma GT) U/L (5 to 35)
• LD Lactate Dehydrogenase U/L (100-225)
• AST (Aspartate aminotransferase) U/L (5 to 45)
• ALT (Alanine aminotransferase) U/L (5 to 45)
• Albumin g/L (38-55)
• Clotting Studies (Prothrombin Time) Seconds (11 to 13.5)
• Total Bilirubin - Normal range is 3 - 18 umol/L (0.174 - 1.04mg/dL)