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Enzymes in Clinical Enzymes in Clinical DiagnosisDiagnosis

By By

Prof. Dr. Hosny FouadProf. Dr. Hosny Fouad

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Plasma enzymes are of two types:Plasma enzymes are of two types:

1.1. A small group of enzymes A small group of enzymes secreted into the blood by secreted into the blood by certain cells e.g.certain cells e.g.the liver secretes zymogens the liver secretes zymogens (inactive form of enzymes) of (inactive form of enzymes) of blood coagulation.blood coagulation.

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2. A large group of enzymes are released from cells during normal cell turnover.These enzymes function intracellularly (inside cells) and have no function in the blood.In healthy individuals, the blood levels of these enzymes are constant, as the rate of release from damaged cells into blood is equal to the rate of removal of enzymes from blood.

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• Elevated enzyme activity in Elevated enzyme activity in blood indicates tissue damage blood indicates tissue damage (due to increased release of (due to increased release of intracellular enzymes).intracellular enzymes).

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A. Plasma Enzymes as A. Plasma Enzymes as diagnostic toolsdiagnostic tools

• Diseases that cause tissue damage Diseases that cause tissue damage result in increased release of result in increased release of intracellular enzymes into the intracellular enzymes into the plasma.plasma.

• Determination of the level of these Determination of the level of these enzymes is used for diagnosis of enzymes is used for diagnosis of heart, liver, skeletal muscle, etc.heart, liver, skeletal muscle, etc.

• The level of these enzymes in The level of these enzymes in plasma correlates with the extent plasma correlates with the extent of tissue damage.of tissue damage.

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• The presence of increased levels of The presence of increased levels of some enzymes in plasma is some enzymes in plasma is diagnostic to damage of a diagnostic to damage of a particular tissue; particular tissue; e.g. The enzyme alanine e.g. The enzyme alanine aminotransferase (ALT) is aminotransferase (ALT) is abundant in the liver and the abundant in the liver and the appearance of elevated levels of appearance of elevated levels of ALT in plasma indicates damage to ALT in plasma indicates damage to the liver.the liver.

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Intracellular Distribution of Intracellular Distribution of Diagnostic EnzymesDiagnostic Enzymes

LiverLiver HearHeartt

PancrePancreasas

SalivarSalivary y GlandsGlands

BonBonee

MusclMusclee

BiliarBiliary y TractTract

ProstaProstatete

LDLD55

ALTALTASTAST

LDLD11

ASTASTCKCK

LPSLPSAMSAMS

AMSAMS ALALPP

CKCK ALPALPGGTGGT

ACPACP

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DISORDERS DIAGNOSED BY DISORDERS DIAGNOSED BY ENZYMESENZYMES

1) Cardiac 1) Cardiac DisordersDisorders..

2) Hepatic 2) Hepatic Disorders.Disorders.

3)3) Skeletal Muscle Skeletal Muscle Disorders. Disorders.

4) Bone Disorders.4) Bone Disorders.

5) Pancreatic 5) Pancreatic Disorders. Disorders.

6) Salivary gland 6) Salivary gland diseae (Mumps) diseae (Mumps)

7) Malignancies 7) Malignancies

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1.Cardiac Disorders:

e.g. Acute Myocardial Infarction (AMI).

1) The myocardium becomes ischemic and

undergoes necrosis.

2) Cellular contents are released into the

circulation. Blood levels of the following enzymes increase:

AST LD1 CK

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2. Hepatic Disorders2. Hepatic Disorders

a)a) Hepatocellular DisordersHepatocellular Disorders:: (1) Viral hepatitis: Hepatitis B & (1) Viral hepatitis: Hepatitis B &

Hepatitis C.Hepatitis C.

(2) Toxic hepatitis: caused by chemicals (2) Toxic hepatitis: caused by chemicals & & Toxins (e.g aflatoxin, Asp. flavus) Toxins (e.g aflatoxin, Asp. flavus)

Increased levels of the following Increased levels of the following enzymes :enzymes :ALTALT ASTAST LDLD55

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b) b) Biliary tract disordersBiliary tract disorders::

The plasma levels of the following The plasma levels of the following enzymes increase: enzymes increase:

ALPALP GGTGGT

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3. Skeletal Muscle 3. Skeletal Muscle DisordersDisorders

• Muscle dystrophy.Muscle dystrophy.• Muscle trauma.Muscle trauma.• Muscle hypoxia.Muscle hypoxia.• Frequent I.M Injections.Frequent I.M Injections.• The plasma levels of the following enzymes The plasma levels of the following enzymes

increase:increase:

CKCK ASTAST

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4. Bone Disorders:4. Bone Disorders:

1)1) Paget’s Bone Disease: caused by Paget’s Bone Disease: caused by increased increased osteoclastic activity.osteoclastic activity.

2) Rickets2) Rickets

3) Osteomalacia:3) Osteomalacia: The plasma levels of the following The plasma levels of the following enzymeenzyme increase: increase: ALPALP

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5. Acute Pancreatitis5. Acute Pancreatitis

• The plasma levels of the following The plasma levels of the following enzymes increase:enzymes increase:

LipaseLipase AMSAMS

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6. Salivary Gland 6. Salivary Gland Inflammation:Inflammation:

• In Mumps:In Mumps:

• The levels of The levels of -Amylase -Amylase (AMS)(AMS) is significantly is significantly increasedincreased

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7. Malignancies7. Malignancies

a)a) Plasma (Acid phosphatase) Plasma (Acid phosphatase) ACP ACP levels increase in: levels increase in:

•Prostatic carcinoma.Prostatic carcinoma.•Bone metastatic carcinoma Bone metastatic carcinoma

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b) Plasma levels of b) Plasma levels of Alkaline Alkaline phosphatase (ALP) phosphatase (ALP) increase increase in:in:

•Pancreatic carcinoma.Pancreatic carcinoma.•Bile duct carcinoma.Bile duct carcinoma.•Liver metastasis.Liver metastasis.

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c) Plasma levels of c) Plasma levels of Total Total Lactate Lactate dehydrogenase (LDH) dehydrogenase (LDH) increase in:increase in:

•LeukemiaLeukemia•Lymphomas.Lymphomas.•Liver metastasis.Liver metastasis.

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B. Isoenzymes and Heart B. Isoenzymes and Heart DiseasesDiseases

• Isoenzymes (or isozymes) are a group of Isoenzymes (or isozymes) are a group of enzymes that catalyze the same reaction.enzymes that catalyze the same reaction.

• However, these enzymes do not have the However, these enzymes do not have the same physical properties (as they differ in same physical properties (as they differ in amino acid sequence).amino acid sequence).

• Thus, they differ in electrophoretic Thus, they differ in electrophoretic mobility.mobility.

• The plasma level of certain isozymes of The plasma level of certain isozymes of the enzyme Creatine kinase (CK) level is the enzyme Creatine kinase (CK) level is determined in the diagnosis of myocardial determined in the diagnosis of myocardial infarction.infarction.

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• Many isoenzymes contain different Many isoenzymes contain different subunits in various combinations.subunits in various combinations.

• CK occurs in 3 isoenzymes, each is CK occurs in 3 isoenzymes, each is a dimer composed of 2 subunits (B a dimer composed of 2 subunits (B & M): CK1 = BB, CK2 = MB and & M): CK1 = BB, CK2 = MB and CK3 = MM, each CK isozyme shows CK3 = MM, each CK isozyme shows a characteristic electrophoretic a characteristic electrophoretic mobility.mobility.

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• Myocardial muscle is the only Myocardial muscle is the only tissue that contains high level of tissue that contains high level of CK2 (MB) isoenzyme.CK2 (MB) isoenzyme.

• Appearance of CK2(MB) in plasma Appearance of CK2(MB) in plasma is specific for heart infarction.is specific for heart infarction.

• Following an acute myocardial Following an acute myocardial infarction,CK2appears in plasma infarction,CK2appears in plasma 4-8 hours following onset of chest 4-8 hours following onset of chest pain (peak is reached after 24 pain (peak is reached after 24 hours).hours).

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Study QuestionsStudy Questions

• Talk about newest markers for Talk about newest markers for myocardial infarction.myocardial infarction.