Clinical Enzymes in Myocardial Infarction Diagnosis

Patient Complaints and Examination

• Pale stool and dark urine are noted
• Complaints include anorexia, nausea, vomiting, pruritus, and severe abdominal pain
• Fever and chills are also reported
• Examination reveals the patient is fat, fertile, and has a palpable gallbladder

Laboratory Findings

• Serum bilirubin (conjugated and unconjugated)
• Urobilinogen
• Urinary bilirubin
• Urinary bile salts
• Serum ALP
• Serum GGT
• Serum 5'-nucleotidase
• Transaminases (mildly raised)

Ultrasound Findings

• Ultrasound shows possible gallstones
• A stone may be impacted in the cystic duct or gall bladder
• Other possible findings include biliary pain or acute cholecystitis, stone in the common bile duct
• The findings might show obstructive jaundice or cholangitis

Clinical Enzymology

• Diagnostic Enzymology is used to diagnose: Myocardial infarction, Liver disease, Bone disease, Muscle disease, and Cancer
• Therapeutic Enzymology provides diagnostic tools

Types of Enzymes in Blood Plasma

• Functional enzymes (in plasma) are attached to endothelial cells in capillaries, examples include lipoprotein lipase and zymogens for blood coagulation
• Non-functional enzymes are functional in cells, example of such enzymes include those involved in cell turnover or disease

Two Major Types of Plasma Enzymes

• Functional enzymes have high concentrations in the plasma and specific substrates
• Examples of functional enzymes include lipoprotein lipase
• Non-functional enzymes have normal low levels due to cell destruction. Elevated levels, indicate tissue necrosis/cell proliferation

Non-Functional Plasma Enzymes

• Enzymes are not normally found in blood but are present in cells
• If found in blood, it usually points to cellular abnormalities (e.g., cell damage, cancer).
• Elevated tissue-specific enzymes or isoenzymes suggest tissue disease

Clinical Importance

• Measuring non-functional plasma enzymes helps diagnose organ diseases reflected by increased enzymes
• Monitoring plasma enzymes before and after treatment assesses treatment efficacy and prognosis

Medically Important Non-Functional Plasma Enzymes

• Amylase is elevated in acute pancreatitis
• Creatine kinase increases in heart, brain, and skeletal muscle diseases
• Lactate dehydrogenase is elevated in heart, liver, and blood diseases
• Alanine transaminase is elevated in liver and heart diseases
• Aspartate transaminase is elevated in liver and heart diseases
• Acid phosphatase is elevated in prostate cancer
• Alkaline phosphatase is elevated in obstructive liver diseases and bone diseases

Enzymes as Diagnostic Markers

• Enzyme activity (not concentration) is measured as IU/mL
• 1 IU/mL equals the activity of an enzyme transforming 1 µmol of substrate/minute
• Correlates with tissue damage
• Predicts prognosis
• Tissue-specific enzymes/isoenzymes reflect damage to the tissue

Myocardial Infarction

• Myocardial infarction (heart attack) can present with nausea, vomiting, sweating, pallor, anxiety, and crushing chest pain, and difficulty breathing
• Diagnostic tools include cardiac enzymes (e.g., CK-MB, LDH, AST, Troponin I & T)

Investigations (Cardiac Markers)

• Values of markers like CK-MB, LDH, AST, Myoglobin, Troponin I & T
• Abnormal activity/peak/duration/time period for the markers vary.

Serum Enzymes in Myocardial Infarction

• Specific enzymes start rising and peaking at specific times after MI onset (e.g., Creatine Kinase rising in 4-8 hours and peaking between 24 and 28 hours)
• Various enzymes have different durations of rising and falling in blood.

Types of Biochemical Markers for Myocardial Infarction

• Cardiac enzymes (isoenzymes) : Total CK, CK-MB activity, CK-MB mass, LDH, AST
• Cardiac proteins: Myoglobin, Troponins

Cardiac Markers (Time Course)

• Graph showing how different cardiac enzyme marker levels change over hours/days following myocardial infarction
• Different cardiac markers have different patterns in blood after MI (rising hours and peak/duration varies)

Cardiac Markers (Serum)

• Graph showing different marker level in blood over different days from start of MI

ECG

• An ECG can show ST elevation during a myocardial infarction.

Criteria for Ideal Markers of Myocardial Infarction

• The ideal markers of myocardial infarction are specific, sensitive, prognostic, and persist for a duration allowing for diagnosis of delayed admission, reliable, simple, inexpensive, and quick.

Cardiac Enzymes (Including Total CK and CK-MB)

• Total CK is non-specific, but CK-MB is more specific; however, it is also present in skeletal muscles (less specific than cardiac troponin)
• CK-MB appears in blood within 4 - 6 hours of MI onset and peaks in 12 - 24 hours.
• CK-MB returns to normal levels after 2-3 days.

Creatine Kinase (CK)

• CK has three isoenzymes: CK-MM in skeletal muscle. CK-BB in brain and CK-MB in heart and skeletal muscle.
• CK-MB was previously a very useful marker for MI diagnosis

Lactate Dehydrogenase (LDH)

• LDH is a tetramer with five isoenzymes, LDH1 and LDH2 predominates in heart
• LDH appears in blood 18-16 hours after MI and peaks in 48 hours.
• LDH usually remains elevated for 5-6 days or longer (up to 14 days)
• LDH is a non-specific marker for other conditions like liver, lung, kidney, etc.

Lactate Dehydrogenase (LDH) Isoenzymes

• LDH isoenzymes have different tissue distributions (HHHH, HHHM, HHMM, HMMM, MMMM).
• LDH1 (HHHH) is found prominently in the myocardium
• Other LDH isoenzymes are in other tissues.

Serum Aspartate Aminotransferase (AST)

• AST is less specific for myocardial infarction than CK-MB.
• It starts rising between 6-12 hours after a MI and peaks in 24-48 hours.

Cardiac Troponins

• Cardiac troponins are highly specific for myocardial injury; cTnI and cTnT are biomarkers
• Appears in blood within 6 hours and peaks in 24 hours following MI
• Stayes in the blood for at least 10 days or more

Myoglobin (MB)

• Myoglobin is a non-specific marker; it is released quickly by damaged muscle
• Myoglobin rises early (within 1 hour following necrosis) and reaches peak in 4-12 hrs
• It's elevated for 0-4 hrs
• Limited/short time period in the blood
• Muscle damage can lead to misdiagnosis

Hepatic Enzymes

• Jaundice, nausea, vomiting, fatigue, weakness
• Elevated enzymes indicate liver damage
• Alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase

Serum Enzymes in Liver Diseases

• Enzyme tests categorize into those detecting hepatocyte damage and those showing cholestasis
• Aminotransferases are indicators of liver cell injury from acute hepatitis

Enzymes that Reflect Cholestasis

• Alkaline phosphatase, 5'-nucleotidase, and gamma-glutamyl transferase are elevated in cholestasis
• Alkaline phosphatase & 5'-nucleotidase are found in hepatocytes
• Gamma-glutamyl transferase found in endoplasmic reticulum and bile duct epithelial cells

Levels of Liver Enzymes in Diseases

• Rapid rise in transaminases (AST and ALT) occurs before bilirubin rise during viral hepatitis

Liver Function Tests (LFTs)

• LFTs assess liver function (e.g., Total protein, albumin, globulin, A/G ratio, Alkaline phosphatase, ALT, AST)
• Specific patterns suggest hepatitis or cirrhosis

Standard Liver Panel

• Standard liver panel includes Albumin, Transaminases (ALT and AST), Alkaline phosphatase, Total bilirubin, Direct bilirubin, Gamma-glutamyl transpeptidase, 5' Nucleotidase, Lactate dehydrogenase, INR

Serum Total Protein and A/G Ratio

• Serum total protein is made of albumin and globulins (a1, a2, β, γ)
• The A/G ratio (albumin/globulin) is an index of disease state, but it's not specific
• Normal A/G ratio is 0.8-2.0

Hepatic Enzymes (Detailed)

• Includes enzymes like aspartate aminotransferase (AST or SGOT) for myocardial infarction, liver disease, or liver cell damage
• Alanine aminotransferase (ALT or SGPT) for liver diseases, liver cell damage, or liver disease/biliary obstruction
• Alkaline Phosphatase (ALP) for liver diseases, biliary obstruction, or osteoblastic bone disease.

Lactate Dehydrogenase (LDH) (Detailed)

• LDH is a tetrameric enzyme with five isoenzymes (HHHH, HHHM, HHMM, HMMM, MMMM) with primarily different tissue-specific distributions.
• LDH is widespread in various tissues, including blood cells, heart muscle.
• LDH is a marker to common injuries and diseases such as heart failure.

Gamma-Glutamyl Transferase (GGT)

• GGT is part of a system moving amino acids.
• Important as it can help determine the reason for increased levels of alkaline phosphatase
• Elevated GGT and ALP occur in biliary duct or some liver diseases but only ALP will be elevated in bone diseases.

Serum Enzymes in Gastrointestinal (GI) Tract Diseases

• Amylase is elevated within 24 hours in acute pancreatitis.
• Further, elevated levels are also seen in perforated peptic ulcers and intestinal obstructions
• Lipase is highly elevated in acute pancreatitis, perforated duodenal ulcers, and intestinal obstructions

Serum Enzymes in Muscle Diseases

• Creatine kinase and aspartate transferase are elevated with muscle diseases like muscle damage

Markers of Muscle Damage

• Creatine kinase (CK) is released by damaged muscle, and its concentration rises steadily for 12 hours, remains elevated for 1-3 days, and then falls.
• Myoglobin has a short half-life.
• Lactate dehydrogenase (LDH) is elevated
• Other markers of muscle damage (aldolase, troponin, carbonic anhydrase)

Enzymes as Tumor Markers

• Enzymes like serum acid phosphatase, serum alkaline phosphatase, serum LDH, B-glucuronidase, leucine amino peptidase (LAP), neuron-specific enolase can help in identifying cancers

This quiz focuses on the various enzymes critical for diagnosing myocardial infarction and understanding tissue damage. It covers significant markers, their roles, and implications in clinical diagnostics. Test your knowledge on enzymes such as LDH, Myoglobin, and others commonly involved in cardiac and pancreatic conditions.