Diagnostic Value of enzymes in Various Diseases

Creatine kinase (CK)

Definition of Creatine kinase (CK):

1. This is a dimeric enzyme that causes the reversible phosphorylation of creatine.
2. CK activity is greatest in striated muscles, the brain, and heart tissues.
3. The kidney has less activity of lipase.
4. The liver and RBCs have no CK activity.

It has subunits:

1. CK-1 is CK-BB.
2. CK-2 is CK- MB.
3. CK-3 is CK – MM.
4. CK enzyme activity increases in skeletal muscles, the cardiovascular system, the brain, and thyroid diseases.
5. CK-MM is increased in:
   1. Muscular atrophy, especially Duchenne’s type.
   2. In progressive muscular dystrophy.
   3. The enzyme level is high in children between 7 to 10 years.
      1. It falls in the older patient.
6. CK-MB is raised after the acute myocardial infection.

CK-MB level in acute myocardial infarction

7. CK-BB is an increase in cerebrovascular diseases.
   1. It increases in the neurosurgical intervention.
   2. In cerebral ischemia.

Gamma-Glutamyl Transferase (GGT)

Definition of Gamma-Glutamyl Trasferase (GGT)

1. GGT is a membrane-bound enzyme in the liver (cells lining the bile ductile and canaliculi).
2. GGT is also seen in proximal renal tubules, the brain, the prostate, and the pancreas (ductules and acinar cells).

Indications for the GGT

1. It is advised for liver diseases.
2. It is advised in alcohol intake to see liver cell injury.
3. It differentiates liver diseases from bone diseases, where alkaline phosphatase is raised.

Pathophysiology of GGT:

1. GGT is responsible for glutathione’s extracellular metabolism (the cells’ main oxidant).
2. Glutathione is its substrate.
3. GGT is present on the cell membranes and assists amino acid transport into the cells.

GGT’s role in amino acids transport

4. GGT is mainly present in the liver cells. It is also presented in the biliary tract epithelium.
   1. GGT is present in the smooth endoplasmic reticulum of liver cells, and it will be increased in case of increased toxins.
      1. GGT is increased in patients when exposed to drugs like barbiturates, warfarin, valproate, Dilantin, methotrexate, and alcohol.
   2. A small amount is found in the kidneys, intestine, heart, brain, pancreas, and spleen.
   3. There is some activity in the capillary endothelial cells.
5. The serum GGT level is increased in the newborn but decreases to the adult level by 4 months.
   1. GGT usually does not increase in bone disease, childhood or adolescence, or pregnancy.
6. GGT is raised by acute liver cell damage and biliary tract obstruction.
7. Its half-life is 7 to 10 days.
8. This enzyme originates from the hepatobiliary system.
9. GGT is the best indicator of occult alcoholism.
10. GGT is lower in women than men. It is significantly high in African-Americans.

Causes of raised GGT:

1. It is raised 2 to 3 times the normal value in heavy drinkers.
   1. It returns to normal after stopping the alcohol in about 3 weeks.
2. It is raised in all forms of liver disease.
3. It is raised in intrahepatic and posthepatic biliary obstruction.
4. The level reaches 5 to 30 times the normal value.
5. This is a more sensitive test for diagnosing obstructive jaundice, cholangitis, and cholecystitis.
6. The rise is earlier than other enzymes and persists longer.
   1. Moderate elevation 2 to 5 times occurs in infectious hepatitis.
   2. A high level was seen in primary or metastatic malignancies.
   3. 2 to 5 times increase seen in fatty liver and drug intoxication.
   4. In acute or chronic pancreatitis, the GGT level may be raised to 5 to 15 times the normal when there is a hepatobiliary obstruction.
7. GGT is always raised in acute pancreatitis. In chronic pancreatitis, it is raised if there is biliary tract involvement or active inflammation.
8. It is normal in a skeletal disease like Paget’s disease and bone malignancy, while alkaline phosphatase is raised.
   1. GGT is raised in alcoholic cirrhosis.
9. In 5% to 30% of patients, GGT is raised in acute myocardial infarction. This is due to the proliferation of capillaries and fibroblasts in granulation tissue. The rise is usually reported after 7 to 14 days of the infarction. Usually, elevation starts 4th to 5th day and reaches a maximum of 8 to 12 days.
10. In pregnancy, bone diseases, and childhood, there is an increase in the alkaline phosphatase, but GGT is normal.
11. The importance of GGT:
    1. GGT differentiates from the liver to nonliver cell injury origin when the alkaline phosphatase level is raised.
    2. GGT is the best test to confirm that raised alkaline phosphatase is from the liver.

Lactate dehydrogenase (LDH)

Sample for LDH

1. It is done in the serum of the patient.
2. A random sample can be used.

Indications for LDH 

1. It is a marker of hemolysis.
2. It is a useful marker of the disease activity in cryptogenic fibrosing alveolitis and extrinsic allergic alveolitis.
3. LDH was the marker of AMI but is now replaced by the Troponin T.

Precautions for LDH

1. Avoid hemolysis, as this will interfere with LDH estimation.
2. Separate the clot immediately from the serum.
3. Avoid heat to the blood sample.

Pathophysiology of LDH

1. LDH is widely distributed in the tissue and has a high concentration in the liver, cardiac muscles, kidneys, skeletal muscles, RBCs, and other tissues.
   1. Less concentration is found in the lungs, smooth muscles, and the brain.

2. Its isoenzymes are:
   1. LD-1 is predominant in the heart, muscles, kidneys, and RBCs.
   2. LD-2 is like LD-1.
   3. LD-3.
   4. LD-4.is more in the liver and skeletal muscles.
   5. LD-5 is more in the liver and skeletal muscles.
   6. LD-6

LDH has 5 isoenzymes:

3. LDH catalyzes the interconversion of lactate to pyruvate.
4. Lactate dehydrogenase is a hydrogen transfer enzyme; it catalyzes the oxidation of L-Lactate to pyruvate.

LDH’s role in chemical reactions

5. The optimum pH for LDH to pyruvate is 8.8 to 9.8.
6. LDH activity is present in all the cells and is found in the cytoplasm of the cells.
7. The enzyme level is variable in concentration in various tissues.
   1. The tissue level is 500 times higher than the serum, so cell leakage increases the serum level.

LDH is raised in:

1. Acute myocardial infarction.
2. A moderate increase may be seen in myocarditis and cardiac failure.
3. Severe shock and anoxia.
4. Megaloblastic anemia.
5. In the case of liver disease.
6. In 1/3 of the cases of renal diseases like tubular necrosis and pyelonephritis.
7. In liver metastatic tumor infiltration.
8. LDH-raised value in the urine is seen in the case of glomerulonephritis, diabetic nephropathy, systemic lupus erythematosus, urinary bladder, and kidney malignancies.
9. CSF infiltration by the granulocytes increases the LDH value.
   1. In bacterial meningitis, there is an increase in LD-4 and LD-5.
10. In cerebrovascular accidents:
    1. Subdural  and subarachnoid hemorrhage increases all isoenzymes of LD, especially LD-3, 4, 5
    2. Where peak level reaches in 1 to 3 days.
    3. It is not related to xanthochromia.
    4. In CNS tumors, there is an increase in the LD-5 in >9% of the cases and decreased level of LD-1: LD-5 ratio.
    5. LD-1: LD-5 ratio <2.5 in the absence of infection or hemorrhage suggests meningeal tumors.
    6. LD-5 in >10% of the cases suggests high-grade malignant tumors.
11. This is normal in angina and pericarditis.

Lipase Enzyme

Definition of lipase

1. Lipase is a glycoprotein enzyme filtered by glomeruli and completely absorbed by proximal tubules.
2. Lipase is more specific than amylase in pancreatic damage.

Pathophysiology of lipase

1. The pancreas is the main organ for lipase secretion, which goes into pancreatic juice.
   1. Lipase may be found in the stomach and intestinal mucosa but doesn’t have a significant role in the processing of fats.
   2. Lipase from the pancreas is secreted into the duodenum, converting triglycerides into fatty acids.
2. Lipase concentration in the pancreas is 100 times greater than in the other tissue.
   1. The difference between amylase in the pancreas and serum is 20,000 times.
   2. A very small amount is found in the serum.
   3. Lipase estimation is very difficult and not reproducible, so not common in the labs.
   4. Lipase hydrolyzes glycerol esters of long-chain fatty acids.
3. Acute pancreatitis:
   1. Lipase enzymes can diagnose it.
   2. The serum lipase level rises slightly later than amylase.
   3. The initial rise is seen in 4 to 8 (3 to 6) hours.
   4. The peak level is 24 hours (another reference says the peak level is after 72 to 96 hours).
   5. The peak remains for a longer time.
   6. The normal level is seen after 8 to 14 days (7 to 10 days).

Lipase enzyme in acute pancreatitis

Lipase level  raised in the following conditions:

1. Acute pancreatitis.
2. Chronic pancreatitis.
3. Acute cholecystitis.
4. Perforating or penetrating peptic ulcer.
5. Obstruction of the pancreatic duct by:
   1. Stones.
   2. Drugs induced.
   3. Partial obstruction with the use of drugs.
6. Small intestinal obstruction.
7. Intestinal infarction.
8. Acute and chronic renal failure with complications.
9. Alcoholism.
10. Diabetic ketoacidosis.
11. Drug-induced acute pancreatitis.

Lipase level decreased:

• It is only seen in the methodology where there is interference by Hemoglobin, heavy metals, and calcium ions.

Lipase level normal in:

1. Values are lower in neonates.
2. Mumps.
3. Macroamylasemia.

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