chemistry unit 3 part 2Cardiac Testing in the Chemistry Lab – Comprehensive Study Notes

Course Context & Logistics

• Medical Laboratory Assistant/Technician (MLA/T) Program – Cardiac Testing in the Chemistry Laboratory module
• Primary reference text: Linne & Ringsrud’s Clinical Laboratory Science (8th Ed.) by Mary Turgeon, Chapter 10, pp. 266-269
• Copyright © 2022 Anderson College – material for internal educational use only

Learning Objectives (Outcomes 5.1 – 5.4)

• Identify the common cardiac markers measured in chemistry labs
• Describe temporal rise & fall patterns of each marker post-myocardial infarction (MI)
• List normal reference ranges & critical (alert) values
• Discuss special specimen-handling or pre-analytical requirements

Epidemiological & Clinical Introduction

• National concern from Canadian Heart Association & Heart & Stroke Foundation
• Traditional risk-factor models focused mainly on white males; newer studies show:
  • Women & Indigenous peoples possess equal or higher MI/stroke risk
  • Gender-specific symptomatology often under-recognized
• Pre-existing conditions increasing risk:
  • Diabetes → dyslipidemia, microvascular changes
  • Chronic kidney disease, hypertension, etc.
• Foundational cholesterol & inflammation analytes:
  • \text{LDL} ("bad" cholesterol) ↑ risk
  • \text{HDL} ("good" cholesterol) ↓ risk
  • \text{CRP} – acute-phase reactant signaling systemic inflammation

Cardiovascular Disease (CVD) Terminology

• Deep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) – venous clots
• Atherosclerosis – arterial plaque accumulation
• Myocardial Infarction (MI) – cardiac muscle necrosis due to ischemia
• Angina – ischemic chest pain; may be stable/unstable
• Dyspnea – shortness of breath; cardinal symptom
• Stroke – cerebral blood-flow occlusion; ischemic or hemorrhagic
• Arrhythmia – irregular rhythm (e.g.
  atrial fibrillation, ventricular tachycardia)

Diagnostic Modalities Beyond Chemistry

• Electrocardiogram (ECG)
• Cardiac/vascular Ultrasound (echocardiography, carotid Doppler)
• MRI (cardiac morphology & viability)
• Exercise/Pharmacologic Stress Test
• Chemistry assays must be correlated with imaging & clinical presentation

Definition & Purpose of Cardiac Markers

• Biomolecules released into blood reflecting myocardial stress/injury
• Historically called “cardiac enzymes”; modern panel includes enzymes, structural proteins, hormones, & acute-phase reactants
• Serial sampling critical because each marker exhibits a characteristic time-course
  • Recommended draws: admission (0 h), 2-4 h, 6-8 h, and 12 h after symptom onset

Current Gold-Standard Marker Panel

• High-sensitivity Troponins (\text{cTnT}_{hs},\ \text{cTnI})
• Myoglobin (MB) – rapid early rule-in/rule-out
• Creatine Kinase-MB (CK-MB) – legacy but still used for timing

Pre-analytical / Specimen Considerations

• Obtain serum or heparinized plasma according to local protocol
• Record exact symptom onset time for kinetic interpretation
• Avoid hemolysis (false ↑ CK-MB, myoglobin)
• Refrigerate or process promptly; some assays require centrifugation within \le 2 h
• Serial specimens should be drawn through separate venipunctures to avoid dilutional error

Troponins (TnT, TnI, TnC)

• Troponin complex regulates actin-myosin interaction in striated muscle
• Laboratory focus: \text{cTnT} & \text{cTnI} (cardiac-specific isoforms)
• Kinetics:
  • Detectable 3–12\ \text{h} post-MI
  • Peak ≈ 24\ \text{h}
  • Remain elevated 4–10\ \text{days} → useful for late presenters
• Analytical advantages: superior sensitivity & specificity vs. CK-MB; detects small infarcts & peri-procedural injury
• High-sensitivity platforms (hs-TnT) allow detection of <14\ \text{ng/L} in healthy population, enabling risk stratification in chest-pain units
• Non-MI elevations (clinician must integrate with ECG/clinical picture):
  • Chronic kidney disease, CHF, PE, arrhythmia, sepsis, strenuous exercise, post-cardiac surgery

Myoglobin (MB)

• Heme protein in skeletal & cardiac muscle; earliest marker
• Rise: 1–3\ \text{h} post-symptom
• Peak: 6–9\ \text{h}
• Return to baseline: \le 24\ \text{h}
• Adult reference: men 30–90\ \text{ng/dL}; women <50\ \text{ng/mL} (unit variability: ng/mL vs ng/dL)
• Lacks cardiac specificity – ↑ with trauma, rhabdomyolysis, renal failure
• Detection methodologies: latex agglutination, ELISA, immunonephelometry, fluoro-immunoassay, point-of-care immunochromatography

Creatine Kinase-MB (CK-MB)

• CK has isoenzymes: MM (skeletal), BB (brain), MB (cardiac predominance)
• MB2/MB1 ratio ↑ is sensitive for early MI
• Rise: 4–6\ \text{h}
• Peak: 12–24\ \text{h}
• Return to baseline: 2–3\ \text{days} – assists in detecting reinfarction if troponin still high
• Reference range 0–16\ \text{U/L} (lab specific)

Homocysteine

• Sulfur-containing amino acid; hyperhomocysteinemia caused by folate, B6, B{12} deficiencies
• Mechanistic role: endothelial damage → atherogenesis
• Marker for CVD, stroke, peripheral vascular disease, particularly when conventional risk factors absent

C-Reactive Protein (CRP) & hs-CRP

• Acute-phase reactant synthesized by liver in response to IL-6
• Traditional CRP monitors infection/inflammation; high-sensitivity CRP (hs-CRP) quantifies low-grade vascular inflammation
• Interpretation (AHA/CDC guidance):
  • <1\ \text{mg/L} = low CVD risk
  • 1–3\ \text{mg/L} = moderate risk
  • >3\ \text{mg/L} = high risk
• Graph of acute-phase proteins depicts CRP & serum amyloid-A as top responders (↑ to >300\% baseline)

Natriuretic Peptides (BNP / NT-proBNP)

• BNP released by ventricular myocytes in response to volume expansion & pressure overload
• Differentiates cardiac vs. pulmonary dyspnea
• Diagnostic & prognostic tool in congestive heart failure (CHF)
• Values influenced by age, renal function, atrial fibrillation

Miscellaneous & Emerging Markers

• Fibrinogen – acute-phase glycoprotein; high plasma levels correlate with atherosclerotic risk
• D-dimer – fibrin degradation product; reflects thrombus turnover in acute coronary syndromes but is non-specific (also ↑ in DVT, PE, sepsis)
• Microalbuminuria – early nephropathy marker; independent predictor of CVD in diabetes & hypertension

Classical Graphical Pattern (Days Post-AMI)

• Myoglobin & CK isoforms → rapid spike (×50 upper limit within <1 day)
• CK-MB → moderate, earlier peak then falls by day 2-3
• Troponin (small vs. large MI) → larger, sustained elevation crossing 10\% CV at 99^{th} percentile, persisting >7 days

Major Modifiable CVD Risk Factors

• \uparrow Blood pressure (hypertension)
• \uparrow Cholesterol / triglycerides (hyperlipidemia)
• Tobacco/vaping
• Type 2 diabetes mellitus
• Sedentary lifestyle
• Diet high in \text{Na}^+, saturated fats, added sugars
• Substance misuse (prescription/recreational)
• Chronic kidney disease
• Non-modifiable: family history, age, sex, ethnicity

Reference Ranges & Critical Values (Institution-specific)*

*Always verify with local laboratory SOPs.

Recommended Serial Testing Intervals (hs-TnT example)

• 0 h (presentation)
• 3 h
• 6 h
• Additional draws if clinical suspicion persists or to detect reinfarction

Practical & Ethical Considerations

• Timely marker reporting can be life-saving; labs must maintain TAT goals (often <45 min for first troponin)
• Over-reliance on single markers may delay treatment; emphasize holistic clinical decision-making
• Sensitive assays may detect “Type 2 MI” (supply-demand mismatch) leading to overtreatment; requires nuanced interpretation
• Equity in CVD research & care: ensure sex- and ethnicity-specific reference intervals & risk algorithms

Study Tips & Concept Integration

• Memorize rise-peak-fall timelines (draw a comparative chart)
• Practice case studies: match marker profiles to early, ongoing, or late MI
• Relate acute-phase reactants to general inflammation chapters (immunology)
• Revisit renal function section when interpreting troponin & BNP in CKD patients
• Use clinical vignettes to differentiate cardiac from skeletal muscle injury via marker patterns

Quick-Look Cheat Sheet

• Troponin: gold standard; 3 h↑, 24 h\text{peak}, 7 d\downarrow
• Myoglobin: 1 h↑, 6 h\text{peak}, 24 h\downarrow
• CK-MB: 4 h↑, 18 h\text{peak}, 3 d\downarrow
• BNP: think volume/pressure → heart failure vs. lung problem
• hs-CRP: chronic low-grade vascular inflammation marker

"Markers tell the timeline; the patient tells the story – always read both."