CEREBROVASCULAR DISEASE MKU Pathology Dr. Lilian Bosire — OVERVIEW Cerebrovascular disease = brain injury from altered blood flow. Stroke = acute-onset neu
CEREBROVASCULAR DISEASE MKU Pathology Dr. Lilian Bosire --- OVERVIEW Cerebrovascular disease = brain injury from altered blood flow. Stroke = acute-onset neurologic deficits from a vascular mechanism, persisting 24 hours. Symptoms resolve <24 hours → Transient Ischemic Attack (TIA) 3rd leading cause of death in the US; #1 cause of neurologic morbidity/mortality Two major mechanisms: 1. Ischemia/Hypoxia — impaired blood supply 2. Hemorrhage — rupture of CNS vessels --- PART 1: ISCHEMIA & HYPOXIA Why the Brain is Vulnerable Feature Detail --- --- % of body weight 1–2% % of cardiac output 15% % of O₂ consumption 20% Metabolism Strictly aerobic — no anaerobic reserve Autoregulates blood flow over wide BP/ICP range, but fails under extreme conditions. Causes of Inadequate Oxygenation Type Mechanism Example --- --- --- Hypoxemia Low blood O₂ content Respiratory failure, high altitude Ischemia Reduced/absent blood flow Cardiac arrest, vessel occlusion Global ischemia Whole-brain underperfusion Severe hypotension, cardiac arrest Focal ischemia Localized vessel occlusion Embolism, thrombosis Factors Determining Tissue Survival 1. Presence of collateral circulation 2. Duration of ischemia 3. Magnitude and rapidity of flow reduction Excitotoxicity Ischemia → release of glutamate Activates NMDA receptors → excessive Ca²⁺ influx → neuronal death The Penumbra "At-risk" zone surrounding the infarct core Neurons die by both apoptosis and necrosis Key therapeutic target — basis of the thrombolysis time window --- PART 2: FOCAL CEREBRAL ISCHEMIA Localized reduction/cessation of blood flow → infarction in the territory of the compromised vessel. Collateral Supply Territory Collateral Supply --- --- Cortex (ACA, MCA, PCA) Circle of Willis + leptomeningeal anastomoses Deep structures (thalamus, BG, white matter) Little or none — most vulnerable In the brain, embolism thrombosis as cause of vascular occlusion. --- CAUSES OF OCCLUSION 1. Embolism (most common) Source Examples --- --- Cardiac Mural thrombi (MI, AF, valvular disease) Arterial Atheromatous plaques from carotids Other Fat (post-fracture), paradoxical, air, tumor Most common territory affected: MCA — equal in both hemispheres Emboli lodge at branch points or areas of preexisting stenosis Fat embolism → "shower embolization" → diffuse dysfunction + hemorrhagic white matter lesions --- 2. Thrombosis Mechanism: acute change in vulnerable atherosclerotic plaque Common sites: carotid bifurcation, origin of MCA, either end of basilar artery Thrombi → progressive narrowing → anterograde extension → may fragment and embolize distally Strongly associated with hypertension and diabetes --- 3. Vasculitis Type Examples --- --- Infectious Syphilis, TB; aspergillosis (immunosuppressed) Non-infectious Polyarteritis nodosa; primary CNS angiitis Other prothrombotic Hypercoagulable states, dissecting aneurysm, drug abuse (cocaine, amphetamines, heroin) --- TYPES OF INFARCTS Type Mechanism Key Feature --- --- --- Non-hemorrhagic (pale) Sustained occlusion, end-organ circulation Most common initial pattern Hemorrhagic (red) Reperfusion after occlusion dissolves Petechiae or confluent bleed into necrotic tissue Venous infarct Dural sinus / deep vein thrombosis Often hemorrhagic --- MORPHOLOGY OF NON-HEMORRHAGIC INFARCT Gross Timeline Time Gross Appearance --- --- 0–6 hours No visible change 48 hours Pale, soft, swollen; gray-white junction blurred 2–10 days Gelatinous, friable; border becomes distinct as edema resolves 10 days–3 weeks Liquefaction → fluid-filled cavity Months Expanding cystic cavity = healed infarct Microscopic Timeline Stage Time Key Features --- --- --- Acute 6–12 hrs "Dead red neurons" — eosinophilic necrosis, nuclear pyknosis/karyorrhexis; cytotoxic + vasogenic edema; neutrophils peak at 48 hrs (less prominent than in MI) Subacute 2 days–3 weeks Foamy macrophages (monocyte-derived + microglia) dominate; reactive astrocytes + new vessels at periphery from 1 week Healed Months Dense glial fiber meshwork + new capillaries; cystic cavity lined by gliotic tissue; pia and arachnoid unaffected Different zones of the same lesion may be at different stages simultaneously — edges heal inward. --- PART 3: INTRAPARENCHYMAL HEMORRHAGE Rupture of small intraparenchymal vessel → primary hemorrhage → acute stroke. Distinct from secondary hemorrhagic transformation of occlusive infarct Peak incidence: ~60 years of age Other contributing causes: coagulation disorders, neoplasms, vasculitis, aneurysms, vascular malformations Patterns & Causes Pattern Location Main Cause --- --- --- Ganglionic hemorrhage Putamen, thalamus, pons, cerebellum Hypertension Lobar hemorrhage Cerebral hemispheres Cerebral Amyloid Angiopathy (CAA) --- HYPERTENSIVE HEMORRHAGE Accounts for 50% of clinically significant hemorrhages Responsible for ~15% of deaths in chronic hypertension Most common site: putamen (50–60%) , then thalamus, pons, cerebellar hemispheres Pathogenesis: Hypertension → vessel wall changes: