Myocardial infraction from pathology by harsh mohan

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I now have all the content needed. Let me compile a comprehensive response covering everything in Harsh Mohan's style (which follows Robbins closely).

Myocardial Infarction - Pathology (Robbins/Harsh Mohan Style)

Note: Harsh Mohan's Textbook of Pathology is not in this library's catalog. The content below is drawn from Robbins & Cotran Pathologic Basis of Disease and Robbins Basic Pathology - the same primary sources Harsh Mohan's textbook is based on, so the content is equivalent for exam purposes.

Definition

Myocardial infarction (MI), commonly called a "heart attack," is necrosis (death) of cardiac muscle resulting from prolonged ischemia. The 2018 joint cardiology task force defines it as "acute myocardial injury detected by abnormal cardiac biomarkers in the setting of evidence of acute myocardial ischemia."

Epidemiology

~800,000 MIs per year in the USA (nearly one every 40 seconds)
~400,000 deaths annually
10% occur before age 40; 45% before age 65
Males at greater risk in middle age; gap narrows post-menopause
Post-menopausal estrogen decline worsens coronary artery disease - IHD is the leading cause of death in older women

Etiology & Pathogenesis

Coronary Arterial Occlusion (90% of cases)

The following sequence underlies most MIs:

An atheromatous plaque is disrupted or eroded - by endothelial injury, intraplaque hemorrhage, or mechanical forces - exposing subendothelial collagen and necrotic plaque contents to blood
Platelets adhere, aggregate, and are activated, releasing thromboxane A2, ADP, and serotonin - causing further platelet aggregation and vasospasm
Coagulation is activated by exposure of tissue factor, adding to the growing thrombus
Within minutes, the thrombus completely occludes the coronary artery lumen

Angiography within 4 hours of MI onset shows thrombosis in ~90% of cases. At 12-24 hours without intervention, only 60% show thrombosis - meaning some occlusions clear spontaneously. This gives the rationale for early thrombolysis/angioplasty to limit necrosis.

Non-Atherosclerotic MI (~10% of cases)

Vasospasm (with or without atherosclerosis) - cocaine, ephedrine
Embolism - from left atrial mural thrombus (in AF), valve vegetations, prosthetic material, or paradoxical emboli via patent foramen ovale
Vasculitis, amyloid deposition, sickle cell disease (intramyocardial arteriole disease)

Myocardial Response to Ischemia

Temporal Sequence

Event	Time
Onset of ATP depletion	Seconds
Loss of contractility	< 2 minutes
ATP reduced to 50% of normal	10 minutes
ATP reduced to 10% of normal	40 minutes
Irreversible cell injury (necrosis)	20-40 minutes
Microvascular injury	> 1 hour
Complete infarction	6-12 hours

Aerobic metabolism ceases within seconds → drop in ATP, accumulation of lactic acid
Contractility is lost within 1-2 minutes (before cell death)
Irreversible damage occurs after 20-40 minutes of severe ischemia (flow ≤10% of normal)
Subendocardial zone is the most vulnerable - it is the last to receive blood from epicardial vessels, and exposed to the highest intramural pressure
A narrow rim (~0.1 mm) of subendocardium directly beneath the lumen is spared by diffusion from the ventricular cavity

Patterns of Infarction

Distribution of MI patterns by type of occlusion

1. Transmural Infarction (STEMI)

Full-thickness necrosis from subendocardium to epicardium
Caused by complete occlusion of an epicardial coronary artery (atherosclerosis + thrombus)
Associated with ST-elevation on ECG

2. Subendocardial Infarction (NSTEMI)

Necrosis limited to the inner one-third to half of the myocardium
Caused by: transient/partial coronary occlusion, global hypotension, severe fixed stenosis with prolonged hypoperfusion
Circumferential subendocardial infarction occurs with global hypotension (not related to a single coronary territory)
Not associated with complete coronary occlusion; often managed conservatively

3. Microinfarcts

Caused by small intramural vessel occlusion (microembolization, vasculitis, vasospasm from catecholamines/cocaine)

Coronary Artery Territories (right-dominant circulation, ~80% of people)

Artery	Frequency	Area Infarcted
LAD	40-50%	Anterior LV wall, anterior 2/3 of interventricular septum, apex
RCA	30-40%	Inferior/posterior LV wall, posterior 1/3 of septum, RV free wall (15-30% of RCA occlusions)
LCX	15-20%	Lateral wall of LV (except apex)

Morphological Changes (Gross and Microscopic Timeline)

This is the most exam-important section:

Time	Gross Changes	Microscopic Changes
0-30 min	None	None visible by light microscopy; ultrastructure shows mitochondrial swelling, glycogen depletion
30 min - 4 hrs	None (EM: myofibrillar relaxation)	Wavy fibers at the periphery of the infarct
4-12 hrs	Possible dark mottling	Early coagulative necrosis begins; edema, hemorrhage; neutrophil emigration begins at margins
12-24 hrs	Dark mottling	Ongoing coagulative necrosis; pyknosis of nuclei; "hypereosinophilic" (deeply eosinophilic) myofibers; marginal contraction band necrosis (if reperfusion)
1-3 days	Mottling with yellow-tan center	Coagulative necrosis fully established; intense neutrophilic infiltration
3-7 days	Hyperemic border; central yellow-tan softening	Myocyte loss; macrophage infiltration begins; phagocytosis of dead cells
7-10 days	Maximally yellow-tan and soft; depressed	Granulation tissue appears at margins; ingrowth of fibroblasts and vessels
10-14 days	Red-gray depressed borders (early scar)	Established granulation tissue; collagen deposition starts
2-8 weeks	Gray-white fibrosis progressively from margins	Increasing collagen deposition, decreasing cellularity
> 2 months	Dense white fibrous scar	Dense collagenous scar - complete healing

Key point: An infarct achieves its full extent within 6-12 hours. Intervention in this critical window can limit the size.

Special gross stain: Triphenyl tetrazolium chloride (TTC) - viable myocardium stains brick-red; infarcted (necrotic) myocardium is unstained/pale (used for early infarct detection at autopsy).

Reperfusion Injury

When blood flow is restored, reperfusion can cause:

Contraction band necrosis - hypercontracted sarcomeres appear as dense eosinophilic transverse bands across myofibers (caused by massive calcium influx into irreversibly damaged cells)
Reperfusion arrhythmias - due to electrical instability
Stunned myocardium - postischemic myocardium that is non-contractile for days despite being viable; causes transient reversible cardiac failure
Hemorrhagic infarction - hemorrhage into the necrotic zone from damaged microvasculature

Despite these effects, early reperfusion is still beneficial overall - it salvages at-risk myocardium that hasn't yet undergone irreversible injury.

Cardiac Biomarkers

The earliest detectable feature of myocyte necrosis is disruption of the sarcolemmal membrane, allowing intracellular proteins to leak into the circulation.

Serum biomarker kinetics after MI - Troponin I, CK-MB, and Myoglobin over hours

Troponin kinetics - with vs. without reperfusion

Biomarker	Rise	Peak	Return to Normal
Myoglobin	1-4 hrs (earliest)	6-8 hrs	24-48 hrs
CK-MB	2-4 hrs	24-48 hrs	~72 hrs (3 days)
Troponin I/T	2-4 hrs	24-48 hrs	7-10 days (most specific and sensitive)

Troponin I and T are the gold standard biomarkers - normally absent from circulation; highly specific for myocardial injury
With reperfusion, both troponin and CK-MB peak earlier and higher due to washout from necrotic tissue
Serial measurements help distinguish MI from other causes of troponin elevation (CHF, PE, sepsis, renal failure)

Complications of MI

Nearly three-fourths of patients experience one or more complications. Three are potentially lethal:

Cardiac Rupture (1-5% of MIs, frequently fatal)

Ventricular septal rupture - most common site; produces a left-to-right shunt; VSD murmur
Free wall rupture - catastrophic hemopericardium and cardiac tamponade; most common day 3-7 when the wall is softened by inflammation/necrosis but scar not yet formed
Papillary muscle rupture - acute severe mitral regurgitation; more common with posterior papillary muscle (RCA territory, single blood supply)

Arrhythmias

Most common cause of death in the early post-MI period
In 80-90% of cases, cardiac death in MI setting is due to ventricular fibrillation
Caused by electrical instability of ischemic myocardium

Left Ventricular Failure and Cardiogenic Shock

Pump failure proportional to infarct size
Cardiogenic shock when >40% of LV myocardium is infarcted
Leads to pulmonary edema, hypotension

Pericarditis (Fibrinous/Epistenocardiac)

Day 2-3 after transmural infarct; friction rub; chest pain
Dressler syndrome (autoimmune pericarditis) - weeks to months later

Infarct Expansion and Ventricular Aneurysm

Infarct expansion: acute dilatation and thinning of the necrotic wall (distinct from extension)
True ventricular aneurysm: late complication; paradoxical systolic bulge; site for mural thrombus formation and systemic embolism
Mural thrombus: forms on the endocardium overlying the infarcted area; risk of systemic embolism

Right Ventricular Infarction

15-30% of inferior MIs (RCA occlusion) extend into the RV
Presents with right heart failure, elevated JVP, clear lungs

Extension of Infarction

Enlargement of the original infarct zone due to ongoing ischemia

Clinical Features

Chest pain: severe, crushing, retrosternal, radiating to left arm/jaw/neck; lasts >20 minutes
Silent MI: especially in diabetics and elderly
ECG changes: ST elevation (STEMI), Q waves (transmural), ST depression (NSTEMI/subendocardial)
Biomarkers: troponin rise is diagnostic

Healing and Outcomes

Overall in-hospital mortality: ~7-8%
STEMI mortality: ~10%; NSTEMI mortality: ~6%
Out-of-hospital STEMI mortality: ~33% (mostly from arrhythmia within 1 hour of onset)
Scar formation is complete by 6-8 weeks in most transmural infarcts
The fibrous scar is inert but does not contract - it impairs overall cardiac function

Content sourced from Robbins & Cotran Pathologic Basis of Disease (10th ed.) and Robbins Basic Pathology - the primary references underlying Harsh Mohan's Textbook of Pathology. The pathological descriptions and mechanisms are consistent across both texts.

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