patoloji-ders-notlari

Title

Serdar Balcı

Ischemic Heart Disease

Serdar BALCI, MD

Myocardial ischemia

Imbalance between cardiac blood supply (perfusion) and myocardial oxygen and nutritional requirements

>90% of cases, secondary to obstructive atherosclerotic vascular disease

Ischemic Heart Disease = Coronary Artery Disease

Causes of IHD

CAD
Increased demand
- Increased heart rate or hypertension
Diminished blood volume
- Hypotension or shock
Diminished oxygenation
- Pneumonia or congestive heart failure
Diminished oxygen-carrying capacity
- Anemia, carbon monoxide poisoning

Ischemic Heart Disease

>70% fixed obstruction → critical stenosis
- Exertion → chest pain
- Stable angina
>90% fixed obstruction
- symptoms even at rest → unstable angina
<50% fixed obstruction
- Plaque rupture
- Early, asymptomatic lesions also risk for acute events
Collateral perfusion
- May be enough if there is slow growth of atherosclerosis for years

Acute coronary syndrome

Acute Plaque Change
- Abrupt thrombosis
- Rupture, fissuring, ulceration
Adrenergic stimulation

Robbins Basic Pathology

Angina Pectoris

Intermittent chest pain

Transient, reversible myocardial ischemia

Typical or stable angina
- Predictable episodic chest pain
- Associated with particular levels of exertion or tachycardia
- Crushing or squeezing substernal sensation, that can radiate down the left arm or to the left jaw (referred pain)
- Pain is relieved by rest (reducing demand) or by vasodilator drugs
Prinzmetal or variant angina
- Occurs at rest
- Caused by coronary artery spasm
- Typically occur on or near existing atherosclerotic plaques
- Completely normal vessel can be affected
- Responds promptly to vasodilators such as nitroglycerin and calcium channel blockers
Unstable angina, crescendo angina
- Increasingly frequent pain
- Associated with plaque disruption and superimposed thrombosis, distal embolization of the thrombus, vasospasm, MI

Myocardial Infarction

Robbins Basic Pathology

Myocardial Infarction

Atheromatous plaque is suddenly disrupted
- Intraplaque hemorrhage, mechanical forces
Subendothelial collagen and necrotic plaque contents exposed to blood
- Platelets adhere, aggregate, activate
- Release thromboxane A2, adenosine diphosphate (ADP), serotonin
Further platelet aggregation and vasospasm
Activation of coagulation by exposure of tissue factor
Within minutes, the thrombus completely occlude the coronary artery lumen

Myocardial Response to Ischemia

Within seconds
- Aerobic glycolysis stops
- Drop in adenosine triphosphate (ATP)
- Accumulation of potentially noxious metabolites
  - Lactic acid
In a minute
- Rapid loss of contractility
- Ultrastructural changes rapidly apparent
- Myofibrillar relaxation, glycogen depletion, cell and mitochondrial swelling
Early changes are potentially reversible
Early treatment important

Severe ischemia (20-40 minutes)

Irreversible damage and myocyte death leading to coagulation necrosis

With longer periods of ischemia

Vessel injury, microvascular thrombosis

Postischemic state

Myocardium remains dysfunctional for several days
Persistent abnormalities in cellular biochemistry
Non-contractile state
- Stunned myocardium
Transient but reversible cardiac failure

Arrhythmias after ischemia

Electrical instability (irritability) of ischemic regions

Massive myocardial damage can cause a fatal mechanical failure

80-90% sudden cardiac death in the setting of myocardial ischemia is due to ventricular fibrillation

Irreversible injury

Irreversible injury of ischemic myocytes first occurs in the subendocardial zone
- The last area to receive blood delivered by the epicardial vessels
- Exposed to relatively high intramural pressures

More prolonged ischemia

Cell death moves through other regions of the myocardium
Infarct in its full extent within 3 to 6 hours
If no therapy
- The infarct can involve the entire wall thickness
- Transmural infarct

Robbins Basic Pathology

Patterns of Infarction

The location, size, and morphologic features of an acute myocardial infarct depend on:
- The size and distribution of the involved vessel
- The rate of development and the duration of the occlusion
- Metabolic demands of the myocardium
- Extent of collateral supply

Robbins Basic Pathology

Left anterior descending (LAD) artery
- **40-50% of all MIs **
- Infarction of the anterior wall of the left ventricle
- Anterior two thirds of the ventricular septum
- Most of the heart apex
- Distal occlusion of the LAD may affect only the apex
Proximal left circumflex (LCX) artery
- 15-20% of MIs
- Necrosis of the lateral left ventricle
Proximal right coronary artery (RCA)
- 30-40% of MIs
- Much of the right ventricle
Posterior third of the septum and the posterior left ventricle are perfused by the posterior descending artery
- Can arise from either the RCA (90%) or LCX
Collateral perfusion may supply other areas

Robbins Basic Pathology

Transmural infarctions
- Involve the full thickness of the ventricle
- Epicardial vessel occlusion
Subendocardial infarctions
- Limited to the inner third of the myocardium
- In the setting of severe coronary artery disease
- Transient decreases in oxygen delivery
  - Hypotension, anemia, or pneumonia
- Increases in oxygen demand
  - Tachycardia or hypertension
Microscopic infarcts
- Vasculitis
- Embolization of valve vegetations or mural thrombi
- Vessel spasm due to elevated catecholamines
  - pheochromocytoma, extreme stress, cocaine

Robbins Basic Pathology

Acute infarct macroscopy

Myocardial infarcts less than 12 hours old
- usually are not grossly apparent
Infarcts more than 3 hours old
- Can be visualized by exposing myocardium to vital stains
- triphenyltetrazolium chloride
- A substrate for lactate dehydrogenase
- This enzyme is depleted in the area of ischemic necrosis (leaks out of the damaged cells)
- Infarcted area is unstained (pale), while old scars appear white and glistening

New acute infarct

Robbins Basic Pathology

Recent subendocardial infarct

Autopsy Pathology: A Manual and Atlas

Infarct macroscopy

12 to 24 hours after MI
- Grossly identified
- Red-blue discoloration
- Trapped blood
Progressively better delineated as soft, yellow-tan areas
10 to 14 days
- Rimmed by hyperemic (highly vascularized) granulation tissue
Succeeding weeks
- Infarcted tissue evolves to a fibrous scar.

Healed ischemic damage in hypertrophic cardiomyopathy

Autopsy Pathology: A Manual and Atlas

4-12 hrs microscopy

Coagulative necrosis
“Wavy fibers” at the edges of an infarct
- Noncontractile dead fibers
Intracellular myocyte vacuolization
- Viable, poorly contractile

Robbins Basic Pathology

Scar formation 6 week

Robbins Basic Pathology

Reperfusion Injury

Mitochondrial dysfunction
- Ischemia alters the mitochondrial membrane permeability, which allows proteins to move into the mitochondria
- Swelling and rupture of the outer membrane, releasing mitochondrial contents that promote apoptosis
Myocyte hypercontracture
- Intracellular levels of calcium are increased as a result of impaired calcium cycling and sarcolemmal damage
- After reperfusion the contraction of myofibrils is augmented and uncontrolled, causing cytoskeletal damage and cell death
Free radicals
- superoxide anion ( - O 2 ), hydrogen peroxide (H 2 O 2 ), hypochlorous acid (HOCl), nitric oxide–derived peroxynitrite, and hydroxyl radicals ( - OH) are produced within minutes of reperfusion
- Cause damage to the myocytes by altering membrane proteins and phospholipids
Leukocyte aggregation
- Occlude the microvasculature and contribute to the “no-reflow” phenomenon
- Leukocytes elaborate proteases and elastases that cause cell death
Platelet and complement activation
- Microvascular injury
- Complement activation

Robbins Basic Pathology

A transmural hemorrhagic infarct from ischemic damage that occurred 2 or 3 days before death

Autopsy Pathology: A Manual and Atlas

Robbins Basic Pathology

Complications of MI

Contractile dysfunction
- Cardiogenic Shock
Papillary Muscle Dysfunction
Myocardial rupture
RV heart failure
Arrhythmias
Pericarditis
Chamber dilation
Mural thrombus
Ventricular aneurysm
Progressive late heart failure

Robbins Basic Pathology

Autopsy Pathology: A Manual and Atlas

Chronic Ischemic Heart Disease

Ischemic cardiomyopathy
- History of previous MI
The compensatory mechanisms (hypertrophy) of residual viable myocardium begin to fail
Left ventricular dilation and hypertrophy
Myocardial hypertrophy, diffuse subendocardial myocyte vacuolization, fibrosis
New episodes of angina or infarction, arrhythmias, CHF, MI