Pathophysiology of Stroke

Sid M. Shah, MD

Assistant Residency Director Assistant Clinical Professor Department of Emergency Medicine Michigan State University East Lansing, MI

Pathogenesis of Stroke: Ischemia & Hemorrhage

Ischemia: lack of circulating blood deprives the neurons of oxygen and nourishment Hemorrhage: Extravascular release of blood causes damage by cutting off connecting pathways, resulting in local or generalized pressure injury
Sid Shah, MD

Acute Ischemic Injury

The occlusion of a large vessel (such as MCA) is rarely complete and cerebral blood flow (CBF) depends on the degree of obstruction, and collateral circulation Many factors influence progression and extent of ischemic injury
Sid Shah, MD

Conditions influencing progression and extent of ischemic injury

Rate & duration of the ischemic event Collateral circulation in the involved area of the brain Systemic circulation & arterial blood pressure Coagulation abnormalities Temperature Glucose
Sid Shah, MD

Pathophysiology at Macro Tissue Level

Cerebral Blood Flow (CBF)
Ischemic Thresholds

Ischemic Penumbra and Window of Opportunity

Sid Shah, MD

CBF & Ischemic Thresholds

Normal CBF 50-60 cc/100 g/minute
Varies in different regions of the brain

CBF 20-30cc/100g/min Loss of electrical activity CBF 10 cc/100g/minNeuronal death

Sid Shah, MD

Ischemic Penumbra & Window Of Opportunity

Ischemic zone that surrounds a central core of infarction with CBF of 25% to 50% of normal and loss of auto regulation Viability of brain tissue is preserved if perfusion is restored within a critical time period (2 to 4 hours?)
Sid Shah, MD

Microcellular Mechanisms of Neuronal Injury

Development of microcirculatory disturbances
Formation of micro thrombi Accumulation of noxious metabolites Interaction of endothelial cells with PMN leukocytes & platelets PMNs trigger neuronal necrosis
Sid Shah, MD

Microcellular Mechanisms of Neuronal Injury: Excitotoxicity

Ischemia depletes neuronal energy stores causing energy dependent membrane ion pumps to fail This results in increased extracellular glutamate concentration Release of excitotoxic Glutamate & Aspartate open up calcium channels resulting in influx of calcium, sodium and chloride and out flux of potassium causing irreversible neuronal damage
Sid Shah, MD

Timing of Neuronal Death

Coagulation necrosis Apoptosis

Sid Shah, MD

Coagulation Necrosis
A process of cell death that evolves over 6 hours to 12 hours Necrotic death is attributed to effects of physical, chemical and osmotic damage to the plasma membrane Morphology of dying cells is distinct from that of cells dying from apoptosis
Sid Shah, MD

Apoptosis
Programmed cell death triggered by ischemia, evolves over 2 hours

Ischemia activates latent suicide proteins that triggers an autolytic process mediated by DNA cleavage
Sid Shah, MD

Major Categories of Ischemic Stroke

Thrombosis Embolism Global-Ischemic or Hypotensive Stroke

Sid Shah, MD

Thrombotic Stroke
Atherosclerosis: the commonest pathology of vascular obstruction leading to thrombosis Other pathological causes:
Fibro muscular dysplasia Arteritis (Giant Cell & Takayasu) Dissection of vessel wall and hemorrhage into atheromatous plaque Hypercoaguability
Sid Shah, MD

Embolic Stroke
Two most common sources of emboli:
Left sided cardiac chambers Artery to artery stroke: as in detachment of a thrombus from ICA at the site of a plaque

Many embolic strokes become hemorrhagic Generally smaller strokes than thrombotic strokes
Sid Shah, MD

Embolism

Sid Shah, MD

Ischemic Stroke Due To Hemodynamic Crisis: Hypotensive Stroke

Any event causing abrupt drop in blood pressure results in critical compromise of CBF (cerebral blood flow) and hence cerebral perfusion. Sites affected by critically low CBF are located at the end of an arterial territory. Hence the term watershed or boundary zone infarct.
Sid Shah, MD

Watershed Infarcts Resulting From Hemodynamic Crisis (Hypotensive Stroke)

Sid Shah, MD

Selective Vulnerability of Neurons to Global Ischemia

Hippocampus: pyramidal cell layer Cerebral cortex: Purkinje cell layer Cerebellar cortex The increased vulnerability of these neurons is due to the abundance of neurotransmitter glutamate in these neurons
Sid Shah, MD

Complications Of Restoration of Blood Flow: Hemorrhage and Edema

Arterial occlusion causes ischemia to capillaries, arterioles and vascular walls in addition to the deleterious effects on neurons Hemorrhage (red infarcts) result when the fragile ischemic or injured vessels rupture after sudden restoration of blood flow Vasogenic edema can also occur following a massive stroke or sudden restoration of blood flow to an ischemic area
Sid Shah, MD

Sid Shah, MD

Factors Associated With Red Infarcts (Hemorrhagic Transformation)

Size of the infarct - bigger infarcts have a higher chance of becoming hemorrhagic Richness of collateral circulation Use of anti-coagulants Treatment with thrombolytic agents
Sid Shah, MD