Research paper on pathophysiology of stroke


Strokes are a leading cause of morbidity and mortality in the developed world. Key to prevention and control of strokes is a thorough understanding of their etiology and the pathophysiologic processes that occur. A review of the literature regarding cerebrovascular disease was undertaken to more fully understand the changes that lead to strokes. The causes are manifold and there are many risk factors that may lead to pathology causing a stroke.
The third leading cause of death in the United States is stroke, it is also the cause of significant neurologic disorders and morbidity. A pathological process involving the blood vessels of the brain causes strokes. The three main processes that may lead to a stroke are a thrombus blocking the vessel, an embolism causing blockage of a cerebral vessel, or the rupture of those vessels. The first two are known as ischemic strokes because they block the blood supply of the brain, the third process is known as a hemorrhagic stroke because bleeding occurs on the brain (Robbins, 2007, p. 863).
The brain needs a steady supply of nutrients in the form of glucose and oxygen delivered from the blood. Approximately 15% of the blood supply, and 20% of the oxygen supply is dedicated for the brain. Global cerebral ischemia occurs when there is a generalized reduction of blood flow to the brain. When the reduction is mild, there may be only a mild confusion, however, when the reduction is longer term or more severe, catastrophic changes leading to death and disability may occur (Robbins, 2007, p. 863).
When an intracranial vessel becomes occluded, there is a reduction in the blood supply to the region of the brain that it supplies. The extent of the diminution of blood flow is dependent on the ability of collateral vessels to supply that area of the brain. When there is absolutely no blood flowing to a region of the brain, death and necrosis of brain tissues occurs very rapidly, in 4-10 minutes. If the level of blood flow is <16-18 ml100g of tissue than neuronal death may occur in approximately one hour. blood flows between 18-20mltypically cause tissues several hours to days (harrison’s, 2008, p. 2513).
If the blood flow to the brain is restored prior to cellular death, the patient may experience what is called a transient ischemic attack. This represents a reversible state of tissue injury and is termed the ischemic penumbra. The penumbra consists of tissue surrounding the area of infarction and can be imaged using MRI techniques – if no therapy is initiated or blood flow is not restored, the tissues will eventually die (Harrison’s, 2008, p. 2513).
Focal infarction of the cerebrum occurs through two different routes. Firstly, there is a necrosis where the cytoskeletal breakdown is fast and results from the lack of energy production in the cell. The second pathway involves apoptosis whereby the nutrient starved cells undergo preprogrammed cellular death. The ischemia leads to cellular death primarily by depriving neuron cells of glucose that is utilized by the cellular mitochondria to produce ATP. When cells are unable to produce ATP the ion pumps on the cells no longer function and the cells depolarize which permits for an influx of calcium ions into the cells. Furthermore, glutamate is released from the synaptic terminals, which leads to further toxicity because this leads to a further calcium influx into the cells. When higher levels of calcium are introduced into the cell body, free radicals are produced because the membranes begin to break down. Free radicals destroy the cells by promoting catalysis, which causes even more damage to the cells. When the ischemia is milder, the favored pathway of breakdown is apoptosis. However, when the ischemia is severe necrosis occurs quickly leading to the catastrophic consequences discussed above (Harrison’s, 2008, p. 2514).
Understanding the causes of strokes is key to preventing them and their recurrence. Atrial fibrillation and atherosclerosis of the carotid vessels are key causes of strokes. Clinical examination will often reveal the causes of the stroke, however, a significant portion of strokes have no quickly discernible cause. Clinical examination should concentrate on the vascular system. Auscultation of the carotid arteries and comparisons of blood pressure on the different limbs is elemental. Furthermore, a thorough examination of the cardiac system is necessary and murmurs and arrhythmias must be examined. Neurologic examinations can aid in the localization of the stroke. Imaging studies are necessary before the initiation of therapies and may include MRI, CT or various modalities of angiography. Furthermore, chest x-rays, electrocardiogram, urinalysis, blood tests, and various microbiological examinations may prove useful (Harrison’s, 2008, p. 2516).
Cardioembolism accounts for approximately 20% of all ischemic strokes. A thrombus forms on the walls of poorly functioning heart tissues that then detaches and enters the circulation. Sometimes the embolism may dissolve rapidly producing only the transient ischemic attack, while other times it may cause complete occlusion of the cerebral vessels leading to a full stroke. These types of strokes are sudden and rapidly progress to neurological deficits. The most common sites for an embolism for the heart to lodge to are the middle cerebral artery and the posterior cerebral artery. The leading cause of these emboli are atrial fibrillation, myocardial infarctions, prosthetic valves, rheumatism, and cardiomyopathy. Various risk factors exist such as old age, hypertension, prior cardioembolisms, mitral valve stenosis, and diabetes. In patients with multiple risk factors, the risk of stroke may be as high as 15% per year (Harrison’s, 2008, p. 2517).
Sometimes only a smaller vessel is occluded and this may lead to what is called a lacunar infarction. There are several clinical manifestation of a lacunar infarction. Motor hemiparesis, where the infarct occurs at the posterior part of the internal capsule of the pons leads to facial, arm, and leg involvement. A sensory stroke occurs when the vessel occluded supplies the thalamus. Ataxic hemiparesis occurs when the ventral pons or internal capsule is involved. Dysarthria and clumsy hand happen when the infarction occurs in the ventral pons or the genu of the internal capsule (Harrison’s, 2008, p. 2519).
Other potential causes of stroke include hypercoagulable disorders, venous sinus thrombosis, sickle cell anemia, fibromuscular dysplasia, temporal arteritis, necrotizing arteritis, drugs, moyamoya disease, reversible posterior leukoencephalopathy, leukoariosis, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. When there are no risk factors for the obvious causes of stroke, it is worthwhile to investigate these less common etiologies (Harrison’s, 2008, p. 2520).
In sum, a stroke is a type of disease that can have various etiologies, but the common basis is the lack of blood supply to a specific region of the brain. The clinical manifestations of the stroke are in direct relation to the area of the brain that becomes necrotic due to the lack of blood supply. This may lead to mild symptoms that go away in the case of transient ischemic attacks, or it may range to severe paralysis and death. Prevention of strokes is based on controlling the risk factors such as dyslipidemia, hypertension, and cardiac abnormalities. With rapid therapy some of the more catastrophic consequences may be avoided, however life long monitoring will become necessary for patients with any history of stroke.

Works Cited:

Kumar, V., et al. (Eds.). (2007). Cerebrovascular Diseases. Robbins Basic Pathology (8th
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Smith, W. S., English, J. D., Johnston, S. C. (2008). Cerebrovascular Diseases. In S. Fauci,
D. Kasper, D. Longo, E. Braunwald, S. Hauser, J. L. Jameson, & J. Loscalzo (Eds.), Harrison’s Principles of Internal Medicine (17th ed.) (pp. 2513-2536). New York: McGraw Hill Medical