PLASMA ENZYMES IN DIAGNOSIS:
Enzymes are specific biologic proteins that catalyze biochemical reactions without altering the equilibrium point of the reaction or being consumed or changed in composition. Enzymes are found in all body tissues and are present in cells at much higher concentrations than in plasma. They frequently appear in the serum following cellular injury or from degraded cells.
ENZYMES OF CLINICAL SIGNIFICANCE
I Aspartate Transaminase (AST): high concentrations in cells of liver, cardiac and skeletal muscle, kidney and erythrocytes. Normal levels- 5–30 U/L
Causes of raised levels: Artefactual (release from erythrocytes in vitro), physiological (neonatal period), hepatobiliary(cirrhosis, cholestatic jaundice, acute viral or toxic hepatitis, liver malignancy),cardiac (myocardial Infarction, cardiac surgery), others(circulatory failure with shock and hypoxia, severe hemolysis).
Causes of raised levels: Hepatobiliary (acute viral or toxic hepatitis, cirrhosis, cholestatic jaundice), cardiac (liver congestion secondary to CCF), others (circulatory failure with shock and hypoxia, surgery or extensive trauma, skeletal muscle disease)
III Lactate Dehydrogenase: widely distributed in the body with high concentrations in cells of cardiac and skeletal muscle, liver, kidney, brain and erythrocytes. NON-SPECIFIC MARKER OF CELL DAMAGE. Normal value- 50- 150 U/L
Causes of raised levels: Artefactual (in vitro hemolysis), cardiac (myocardial infarction), circulatory failure with shock and hypoxia,hemolytic disorders (megaloblastic anemia, acute leukemias and lymphomas) ,liver (viral hepatitis), others (malignancy of any tissue, skeletal muscle disease, pulmonary embolism, infections)
IV Creatine Kinase: Most abundant in cells of cardiac, skeletal muscle and brain. Normal value: Total CK — 25–200 U/L CK-MB — 0–4ng/ml
Three isoenzymes : CK-BB (CK-1)- predominantly in brain, smooth muscle of gastrointestinal tract and genital tract,
CK-MB (CK-2)- predominantly in cardiac muscle and to a lesser extent, skeletal muscle. ALWAYS ELEVATED IN MYOCARDIAL INFARCTION. CK-MM (CK-3)- predominantly in skeletal and cardiac muscle.
Causes of raised levels: Artefactual (in vitro hemolysis), muscular disorders and rhabdomyolysis, physical exertion(moderate exercise,, muscle cramp, following an epileptic fit),
V Amylase: breaks down starch and glycogen to maltose. High concentration in pancreas and salivary glands.
Normal value: 30–125 U/L
Causes of raised levels: Acute pancreatitis,perforated peptic ulcer, acute cholecystitis, salivary gland disorders(mumps,sjogren’s syndrome, salivary calculi), severe glomerular impairment( due to reduced clearance), macroamylasemia, diabetic ketoacidosis.
VI Alkaline Phosphatase (ALP): present in most tissues but very high concentrations in osteoblasts of bone , cells of hepatobiliary tract, intestinal wall, renal tubules and placenta. Adult plasma ALP derived mainly from bone and liver. Normal Value- 50–100 U/L
Causes of raised levels: Physiological ( last trimester of pregnancy,preterm infants, age), bone disease ( rickets, osteomalacia, paget’s disease of bone, secondary malignant deposit in bones), hyperparathyroidism, liver disease , malignancy (with bone or liver involvement). A PLACENTAL-LIKE (REGAN) ISOENZYME FOUND IN MALIGNANT DISEASE ESPECIALLY CARCINOMA OF BRONCHUS .
Causes of low levels: Arrested bone growth (achondroplasia, cretinism, severe ascorbate deficiency), hypophosphatemia( autosomal recessive disorder associated with rickets or osteomalacia)
Prostatic Acid phosphatase- 0 -3 U/dl
Normal value: 6–50 U/L
Causes of raised levels: induction of enzyme synthesis by drugs or alcohol , cholestatic liver disease (IN CHOLESTATIC JAUNDICE OF PREGNANCY GGT DOES NOT INCREASE), hepatocellular damage( MEASUREMENT OF PLASMA TRANSAMINASES IS A MORE SENSITIVE INDICATOR OF HEPATOCELLULAR CONDITIONS).
NOTE: Very high plasma GGT out of proportion to those of transaminases may be due to:
IX Plasma Cholinesterase: Two isoenzymes- i) cholinesterase (pseudocholinesterase)– found mostly in plasma and synthesized mainly in the liver. ii) acetylcholinesterase– found predominantly in erythrocyte and nervous tissue.
Causes of raised levels: recovery from liver damage(actively growing hepatocytes), nephrotic syndrome.
Causes of low levels: hepatic parenchymal disease (reduced synthesis), ingestion or absorption through the skin of such anticholinesterases as organophosphates, inherited abnormal cholinesterase variants with low biological activity.
SUXAMETHONIUM SENSITIVITY: Suxamethonium(succinylcholine),the muscle relaxant used intraoperatively, is usually broken down by plasma cholinesterase and this limits the duration of its action. Giving suxamethonium to patients with a low cholinesterase activity,usually due to an enzyme variant is often followed by prolonged periods of apnea(scoline apnea) leading to a need for ventilatory support post-surgery. Identification of susceptible patients and their affected relatives is important. All affected individuals should carry a WARNING CARD or ‘MEDIC ALERT’ BRACELET.
X Lipase: found primarily in the pancreas, although it is also present to a lesser extent in the stomach and small intestine. Normal value: 10–150 U/L
Causes of raised levels: Acute pancreatitis (it is more specific than amylase in diagnosing acute pancreatitis), Elevations have been reported in cases of penetrating duodenal ulcers and perforated peptic ulcers, intestinal obstruction, and acute cholecystitis. In contrast to amylase, lipase levels are normal in conditions of salivary gland involvement.
XI Glucose-6-Phosphate Dehydrogenase (G-6-PD): occurs in adrenal cortex, spleen, thymus, lymph nodes, lactating mammary gland, and erythrocytes. Little activity is found in normal serum.
Causes of raise levels: Increased levels of G-6-PD in the serum have been reported in myocardial infarction and megaloblastic anemias ( raised levels are not diagnostic of these diseases)
G-6-PD deficiency- G-6-PD deficiency is an inherited sex-linked trait. The disorder can result in several different clinical manifestations, one of which is drug-induced hemolytic anemia. A deficiency of G-6-PD results in an inadequate supply of NADPH and, ultimately, in the inability to maintain reduced glutathione levels. When erythrocytes are exposed to oxidizing agents, hemolysis occurs because of oxidation of hemoglobin and damage of the cell membrane.
XII Drug Metabolising Enzymes :Drug-metabolizing enzymes function primarily to transform xenobiotics into inactive, water-soluble compounds for excretion through the kidneys. Metabolic enzymes can also transform inactive prodrugs into active drugs, convert xenobiotics into toxic compounds, or prolong the elimination half-life.
CYP 450 enzymes are a superfamily of isoenzymes that are involved in the metabolism of more than 50% of all drugs. These enzymes that contain heme molecules, and they are given the name CYP450 because they absorb the maximum amount of light at 450 nm. More than 500 CYP450 enzymes that have been identified.