Cerebrovascular diseases (hypoxia, ischemia, infarction)

1. Overview

Cerebrovascular disease = any brain abnormality caused by a pathologic process involving blood vessels.

Three Main Processes

• Thrombotic occlusion of vessels.
• Embolic occlusion of vessels.
• Vascular rupture.

Consequences

• Thrombotic/embolic → loss of O₂ supply → cerebral ischemic injury + infarct.
• Rupture → intracranial hemorrhage → direct tissue damage.

Stroke

• Acute onset of neurological symptoms from rapid loss of brain function due to disturbance in blood supply.
• Clinical manifestation of the above conditions.

2. Hypoxia vs Ischemia

Brain Demand

• Receives 15 % of resting cardiac output.
• Consumes 20 % of total body oxygen.
• Autoregulation keeps blood flow constant despite Δ perfusion pressure.

Hypoxia

• Low partial pressure of O₂.
• Causes: high altitude, impaired O₂ carrying capacity (anemia, CO poisoning), inhibition of O₂ use (cyanide).
• Better tolerated than ischemia → typically does not cause much damage alone.

Ischemia

• Obstruction of tissue perfusion → fully saturated blood cannot reach the brain.
• Mechanism behind infarcts.

3. Global Cerebral Ischemia

Definition

• Generalized cerebral ischemia + hypoxia.

Causes

• Cardiogenic shock.
• Cardiac arrest.
• Severe arrhythmia (↓ pumping → ↓ perfusion).
• ↑ Intracranial pressure.
• Severe hypotension.

Selective Vulnerability

Most sensitive cells:

• Pyramidal cells of hippocampus (CA1 / Sommer sector).
• Purkinje cells of cerebellum.
• Pyramidal cells of neocortex (layers 3, 5, 6).

Clinical Features

• Mild ischemia: transient confusional state.
• Severe global ischemia: widespread neuronal death.
  • Survivors: deeply comatose / vegetative state.
  • Brain dead → flat EEG + absence of respiratory drive.
  • Mechanical ventilation in such cases → brain undergoes autolytic process → “respirator brain”.

Border Zone (Watershed) Infarcts

• Areas between major cerebral arteries are not perfused properly.
• More susceptible to ischemia → wedge-shaped infarcts.
• Typically hemorrhagic (collateral flow maintained) → encephalomalacia rubra.

Morphology

• Early: swollen brain, wide gyri, narrowed sulci, poor gray-white demarcation, herniation.
• Late: necrosis, shrinking brain, reactive gliosis.

4. Focal Cerebral Ischemia

Definition

• Reduced blood flow to a particular brain region → ↑ risk of cell death.
• Cerebral artery occlusion → focal ischemia → infarction.

Causes

A) Embolism (#1 cause of cerebral infarction)

• Thromboembolism from carotid bifurcation (most common source).
• Cardioembolism: atrial fibrillation, valvular disease, mural thrombus post-MI.
• Paradoxical emboli via patent foramen ovale.
• Middle cerebral artery (MCA) — most commonly affected.

B) Thrombosis (Atherosclerosis)

• Atherosclerosis of cerebral arteries → in-situ thrombosis.
• Below Circle of Willis = well tolerated (collaterals).
• Above CoW = poorly tolerated (end-arteries).
• Basilar artery + MCA most frequently damaged.

C) Vasculitis

• Usually polyarteritis nodosa, primary CNS vasculitis.

5. Lacunar Infarcts

• One of the most important effects of hypertension on the brain.
• Occlusion of penetrating arteries → supply deep structures (putamen, thalamus, caudate, pons, internal capsule).
• HTN → hyaline arteriolosclerosis → narrowing → ischemia → small necrosis → lacunar infarcts.
• Small (mm-sized) localized infarcts in deep gray matter.
• Clinical syndromes: pure motor, pure sensory, ataxic hemiparesis.

6. Morphology of Infarcts

A) Non-hemorrhagic (“White” / Anemic) Infarct

• Stages: encephalomalacia alba → flava → cysta post encephalomalacia.

Time	Changes
First 6 hours	No changes
48 hours	Tissue pale, soft, swollen; red neurons appear
2–10 days	Soft, fragile, demarcated; neutrophilic granulocytes
10–20 days	Liquefied tissue (encephalomalacia grisea/flava) → fluid-filled cavity; mononuclear phagocytes
Months	Cystic cavity remains

B) Hemorrhagic (“Red”) Infarct (Encephalomalacia Rubra)

• Reperfusion of ischemic infarct (collaterals or dissolution of embolus).
• Venous obstruction → blood blocked → hemorrhage.
• Border zone infarcts — hemorrhagic since some flow is maintained.

7. Summary Table

Type	Mechanism	Key features
Global ischemia	Cardiac arrest, shock, ↑ ICP	Hippocampal CA1, Purkinje, cortex layers 3/5/6; watershed infarcts; respirator brain
Focal ischemia (embolic)	Carotid bifurcation, AF, MI	MCA most affected; #1 cause of infarction
Thrombotic	Atherosclerosis	Basilar + MCA
Lacunar infarct	HTN → hyaline arteriolosclerosis	Putamen/thalamus/caudate/pons/IC; pure motor/sensory syndromes
White infarct	Anemic; encephalomalacia alba/flava	Liquefactive necrosis → cavity
Red infarct	Hemorrhagic; encephalomalacia rubra	Reperfusion, venous block, border zone

💡 High-yield: Brain = 15 % CO + 20 % O₂; hypoxia tolerated > ischemia. Global ischemia → selective vulnerability: hippocampal CA1 (Sommer sector) + Purkinje cells + neocortex 3/5/6; border zone (watershed) infarcts — wedge-shaped, hemorrhagic. Focal ischemia: #1 cause = embolism (carotid bifurcation, AF, MI), MCA most affected; thrombosis from atherosclerosis (basilar + MCA). Lacunar infarcts = HTN → hyaline arteriolosclerosis of penetrating arteries; deep gray (putamen/thalamus/caudate/pons/IC). Infarct morphology: 0–6 h no change, 48 h red neurons, 2–10 d neutrophils, 10–20 d liquefactive necrosis → cyst. Red (hemorrhagic) infarct = reperfusion / venous obstruction / watershed (encephalomalacia rubra).