Sid Shah, MD
Pathophysiology of Stroke Sid Shah, MD
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Introduction The two major mechanisms causing brain damage in stroke are, ischemia and hemorrhage. In ischemic stroke, which represents about 80% of all strokes, decreased or absent circulating blood deprives neurons of necessary substrates. The effects of ischemia are fairly rapid because the brain does not store glucose, the chief energy substrate and is incapable of anaerobic metabolism.1 Non-traumatic intracerebral hemorrhage represents approximately 10% to 15% of all strokes. Intracerebral hemorrhage originates from deep penetrating vessels and causes injury to brain tissue by disrupting connecting pathways and causing localized pressure injury. In either case, destructive biochemical substances released from a variety of sources play an important role in tissue destruction. Focal Ischemic Injury A thrombus or an embolus can occlude a cerebral artery and cause ischemia in the affected vascular territory. It is often not possible to distinguish between a lesion caused by a thrombus and one caused by an embolus. Thrombosis of a vessel can result in artery-to-artery embolism. Mechanisms of neuronal injuy at the cellular level are governed by hypoxia or anoxia from any cause that is reviewed below. At a gross tissue level, the vascular compromise leading to acute stroke is a dynamic process that evolves over time. The progression and the extent of ischemic injury is influenced by many factors.2-5 Rate of onset and duration: the brain better tolerates an ischemic event of short duration or one with slow onset. Collateral circulation: the impact of ischemic injury is greatly influenced by the state of collateral circulation in the affected area of the brain. A good collateral circulation is associated with a better outcome. Health of systemic circulation: Constant cerebral perfusion pressure depends on adequate systemic blood pressure. Systemic hypotension from any reason can result in global cerebral ischemia. Hematological factors: a hypercoagulable state increases the progression and extent of microscopic thrombi, exacerbating vascular occlusion. Temperature: elevated body temperature is associated with greater cerebral ischemic injury. Glucose metabolism: hyper- hypoglycemia can adversely influence the size of an infarct.
Pathophysiology of Stroke Sid Shah, MD Cerebral Blood Flow
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Normal cerebral blood flow (CBF) is approximately 50-to 60 ml/100g/ Min and varies in different parts of the brain. In response to ischemia, the cerebral autoregulatory mechanisms compensate for a reduction in CBF by local vasodilatation, opening the collaterals, and increasing the extraction of oxygen and glucose from the blood. However, when the CBF is reduced to below 20 ml/100g/min, an electrical silence ensues and synaptic activity is greatly diminished in an attempt to preserve energy stores. CBF of less than 10ml/100g/min results in irreversible neuronal injury.1,6-11 Mechanisms of neuronal injury Formation of microscopic thrombi responsible for impairment of microcirculation in the cerebral arterioles and capillaries is a complex phenomenon. Formation of a micro thrombus is triggered by ischemia-induced activation of destructive vasoactive enzymes that are released by endothelium, leucocytes, platelets and other neuronal cells. Mechanical “plugging” by leucocytes, erythrocytes, platlets and fibrin ensues.12 At a molecular level, the development of hypoxic- ischemic neuronal injury is greatly influenced by “overreaction” of certain neurotransmitters, primarily glutamate and aspartate. This process called “excitotoxicity” is triggered by depletion of cellular energy stores. Glutamate, which is normally stored inside the synaptic terminals, is cleared from the extracellular space by an energy dependent process. The greatly increased concentration of glutamate (and aspartate) in the extracellular...