Pathophysiology and Pharmacology - Cerebrovascular Accident - Case Study Example

Pathophysiology and Pharmacology Pathophysiology and Pharmacology A Cerebrovascular Accident also referred to as a stroke is an acute neurologic dysfunction due to focal disturbance of cerebral blood. Ischemia or hemorrhage cause it. Ischemic Cerebrovascular Accident account for 85 percent of strokes of known aetiology. Haemorrhagic Cerebrovascular Accident accounting for the remaining 15 percent (Purushothaman et al. 2014). A stroke can use neurologic damage, disability or death depending on the duration of focal disturbance of cerebral blood. Transient ischemic attacks intensify the risk of a subsequent stroke. An aneurysm or the rupture of a cerebral blood vessel causes haemorrhagic Cerebrovascular Accident. This causes blood to accumulate compressing the brain. There are two types of haemorrhagic strokes. Which include intracerebral, and subarachnoid categorized based on the disease aetiology (Ewan et al. 2010). Ischemic Cerebrovascular Accident is caused by the interruption of blood supply to the cerebral tissue. It has multiple etiologic mechanisms and clinical manifestations. The ischemia is caused by thrombosis, embolism, arterial luminal obliteration, venous congestion and systemic hypoperfusion (Laredo et al. 2011). An Ischemic thrombotic stroke is caused by the development of a clot that obstructs the blood vessel. Pathology in the local endothelium is the common trigger of thrombosis. The most common pathological feature of vascular obstruction is the chronic inflammation disease Atherosclerosis. Atherosclerotic plaques usually form at bifurcation points of vessels and high shear stress points. They overexpress plasminogen activator inhibitor-1 that inhibits the enzyme plasminogen activator, which converts plasminogen to plasmin that degrades plasma proteins (Jorge et al. 2010). Plasmin is essential in fibrinolysis. Therefore, inhibition of activation promotes the formation of blood clots. Endothelial surface injury triggers an inflammatory reaction recruiting cytokines and peroxides. These substances trigger the expression of P-selectin, E-selectin and intercellular adhesion molecule-1 by the endothelial cells molecules necessary for the adhesion of recruited leukocytes to the endothelial wall. They migrate into the intima forming a fatty streak that are then infiltrated by macrophages forming plaques and accumulating lipids to form foam cells (Santos et al. 2012). Plaques can enlarge and occlude blood vessels, become ulcerated, calcify, develop thrombosis, form embolus or lead to the formation of an aneurysm. Ulceration occurs when the atherosclerotic plaques luminal aspect is degraded by metalloproteinase leading to in situ thrombosis or embolization (Jansen et al. 2013). Chronic bacterial infection by Chlamydia pneumonia has been associated with increased risk of the development of atherosclerotic plaques. An embolic stroke is caused by a material from a distance source that reaches the brain through the cerebral circulation. It travels and lodges in cerebral vessels causing an ischemic embolic stroke (Sharma et al. 2014). The most common source of a thromboembolism is the heart. Atrial fibrillation and arterial flutter increase the risk of ischemic embolic stroke (Madan et al. 2010). These cardiac arrhythmias are characterized by stasis in the posterior left atrium and appendage, which increase the risk of thrombus formation. Endocarditis caused by infections, malignancy, and various inflammatory conditions may release emboli to the cerebral circulation leading to an ischemic stroke. Ulceration of atherosclerotic plaques or their mechanical disruption from the aorta and carotid arteries can occur during cardiac surgery causing embolization of cholesterol and thrombi (Oliva-Moreno et al. 2013). This is referred to as artery-to-artery embolization. Diseases such as pulmonary arteriovenous fistula and patent foramen compromise the pulmonary capillary bed affecting its functionality in preventing embolization from the systemic circulation and from entering the cerebral circulation. Loss of arterial pressure causes systemic hypoperfusion leading an ischemic stroke. Many processes can cause this; however, the most common cause is cardiac. Arrhythmia and myocardial infarction cause a generalized loss of arterial pressure resulting in an ischemic stroke (Srikanthan et al. 2015). The watershed region of the brain, which is at the distal edges of the arterial tree is the most affected by this kind of cerebrovascular accident. Obliteration of the arterial lumen also causes an ischemic stroke (Emilio et al. 2010). It is luminal narrowing caused by inflammatory vasculitis, noninflammatory vasculopathy, vasospasm that lead to vasoconstriction and extrinsic masses causing compression. Venous congestion as a result of cerebral venous thrombosis affects forward flow and may lead to infarction. Transient Ischemic Attacks Transient ischemic attacks are short periods of focal loss of brain function lasting for less than twenty-four hours. They are attributable to ischemia. Therefore, the mechanisms in transient ischemic attacks are same as those of ischemic cerebrovascular accident. Amaurosis fugax also referred to as monocular blindness may occur. They resolve within five to ten minutes (McSharry et al. 2014). Transient ischemic attacks and Amaurosis fugax indicate a risk of subsequent ischemic stroke. These attacks are often associated with carotid artery disease, accounting for 80% of the total recorded attacks. 40 percent of the cerebrovascular accident are preceded by transient ischemic attacks and, therefore, patient treatment following an attack should be preventative of the potential stroke (Croot et al. 2014). Transient ischemic attacks have also been associated with coronary heart disease. Pathophysiology of Ischemic Stroke Ischemia reduces cerebral blood flow. The brain issue is dependent on aerobic metabolism with glucose as the sole energy source. However, reduced haemoglobin and glucose concentrations effects on the brain tissue seem less detrimental when compared to cerebral ischemia. Reduction of cerebral blood flow results in accumulation of toxic waste products such as reactive oxygen species that may trigger an inflammatory response (van Rooij et al. 2015). Severe ischemia reduces perfusion pressure to less than 30 mmHg causing bioenergetics failure. At this level of ischemia, the concentration of phosphocreatine and adenosine triphosphate (ATP) reduce and that of adenosine monophosphate (AMP), as well as adenosine diphosphate (ADP) increase. These bioenergetics changes are detrimental to the neurons. The Na+/K+-ATPase pump in the central nervous system maintains the ion gradient crucial for neuronal membrane potential. This accounts for the bulk of the brains metabolic demand, about 70 percent. Mitochondrial production of ATP ceases following uncoupling oxidative phosphorylation from oxygen consumption in ischemic conditions and the levels of adenosine triphosphate (ATP) decline (Timlin & Petri 2013). Within about two minutes, the intracellular adenosine triphosphate stores are depleted. The neuronal cells are depolarized, with the influx of calcium and sodium and efflux of potassium. Disaggregation of microtubules, proteolysis and lipolysis, destroy the cells in the infarct core. In the penumbra, cellular metabolism is preserved with the diminished blood flow. Membrane depolarization also triggers the release of neurotransmitters. The uptake of the neurotransmitter glutamate by the neurons and glia is impaired. N-methyl-D-aspartate receptors are activated leading to calcium influx in the neurons in the vicinity causing excitotoxicity that causes cell death. Depolarization and consequential excitotoxicity are further enhanced by cortical spreading depressions from the infarct core. These processes cause oxidative and nitrative stress (Chen et al. 2014). Inflammatory response results in apoptosis of tissue on the periphery of the infarct core. Cytotoxic oedema also occurs as water moves into the cell since greater sodium, and chloride influx than potassium efflux occurs following the destruction of the ion pumps and channels. The extent of ischemic damage is dependent on time. Restoration of cerebral blood flow one to two hours after the event can prevent irreversible damage. The blood flow should be restored before cytotoxic oedema progresses to vasogenic oedema following the interruption of the blood-brain barrier that causes ischemic brain injury (Mortimer et al. 2012) Signs and Symptoms of Cerebrovascular Accident and Transient Ischemic Attack The signs and symptoms of cerebrovascular accident and transient ischemic attack vary depending on the affected blood vessels and location of the brain and given the fact that the brain controls a wide range of activities. The signs and symptoms of a transient ischemic attack, however, last for a shorter period (Purroy et al. 2014). Other diseases may also cause the signs and symptoms, however with a stroke; the onset of neurological symptoms is sudden. The common signs and symptoms include; numbness of the one body side, the face, leg or arm, dysarthria, aphasia, monocular blindness, diplopia (double vision). Other manifestations include dysconjugate gaze, blurred vision, dizziness, hemineglect, dysphagia, vertigo, ataxia (gait unsteadiness), frequent falls, a sudden excruciating headache, memory loss and personality change. The Case Study Greta Ainija Balodis medical history shows she previously suffered and was treated for hypertension and transient ischemic attack. This diagnosis, therefore, means that Greta was at risk of a subsequent ischemic stroke. She is prescribed Atenolol and Panadol. Atenolol is a beta-blocker an effective drug for hypertensive patients who have experienced a cerebrovascular accident. Greta presents with signs and symptoms of the ischemic cerebrovascular accident as she is gardening. She started to feel a headache coming on, dizziness and nauseous. She also notices her mouth and eye were drooping on the left side of her face. Another symptom is her frequent falls. At the hospital, Greta is diagnosed with cerebral vascular accident (CVA) and atrial fibrillation, which has been shown to intensify the risk of ischemic stroke. She is first released to a Specialist Stroke Rehabilitation Unit in a rehabilitation facility where she recovers and then discharged home. The medications prescribed are aspirin, clopidogrel, and digoxin. Several antiplatelet agents are used to prevent recurrence of the cerebrovascular accident. This includes aspirin, ticlopidine, clopidogrel, and dipyridamole. Aspirin has been shown to lessen morbidity and mortality associated with cerebrovascular accidents. It is effective in both cardiovascular and cerebrovascular events. Aspirin prevents the development of thromboxane A2, which has vasoconstrictive and proagggregetory activity by inhibiting the enzyme cyclooxygenase. It is effective in low doses; however, in high doses it inhibits prostacyclin. Clopidogrel is more effective in stroke prevention than aspirin for patients with coronary and peripheral heart diseases and cerebrovascular conditions. The cardiac glycoside digoxin is used to treat the atrial fibrillation. The case study exemplifies the pathophysiology, symptoms and treatment of cerebrovascular accident. It also includes the psychological effects of the disease on the patient and the patient’s family. Bibliography Chen, P.-S, Cheng, C.-L, Kao, Y.-H, Yeh, P.-S, & Li, Y.-H 2014 ‘Impact of early statin therapy in patients with ischemic stroke or transient ischemic attack’, Acta Neurol. Scand, Vol. 129, no. 1, pp. 41–48. Croot, E, Ryan, T, Read, J, Campbell, F, O’Cathain, A, & Venables, G 2014, ‘Transient ischaemic attack: a qualitative study of the long term consequences for patients’, BMC Fam. Pract, Vol. 15, no. 174, pp. 2–15. Emilio S, Turrina, C, & Valsecchi, P 2010, ‘Cerebrovascular Accidents in Elderly People Treated with Antipsychotic Drugs: A Systematic Review’, Drug Saf, Vol. 33, no. 4, pp. 273–288. Ewan, L, Kinmond, K, & Holmes, P 2010, ‘An observation-based intervention for stroke rehabilitation: experiences of eight individuals affected by stroke’, Disabil. Rehabil, Vol. 32, no. 25, pp. 2097–2106. Jansen, J, Rozeboom, W, Penning, C, & Evenhuis, H 2013, ‘Prevalence and incidence of myocardial infarction and cerebrovascular accident in ageing persons with intellectual disability’, J. Intellect. Disabil. Res, Vol. 57, no. 7, pp. 681–685. Jorge, R, Starkstein, S, & Robinson, R 2010, ‘Apathy Following Stroke’, Apathie Consécutive À Un Accid. Vasc. Cérébral, Vol. 55, no. 6, pp. 350–354. Laredo, L, Vargas, E, Blasco, A, Aguilar, M, Moreno, A, & Portolés, A 2011, ‘Risk of Cerebrovascular Accident Associated with Use of Antipsychotics: Population-Based Case-Control Study’, J. Am. Geriatr. Soc, Vol. 59, no. 7, pp. 1182–1187. Madan, V, Kingston, H, Jamieson, L, Goyal, N, & Ead, R 2010, ‘Muckle–Wells syndrome/neonatal-onset multisystem inflammatory disease overlap associated with myelodysplasia and cerebrovascular accident’, Clin. Exp. Dermatol, Vol. 35, no. 7, pp. 752–755. Mc Sharry, J, Baxter, A, Wallace, L, Kenton, A, Turner, A, & French, D 2014, ‘Delay in seeking medical help following transient ischemic attack (TIA) or “Mini-Stroke”: A Qualitative Study’, PLoS ONE, Vol. 9, no. 8, pp. 1–9. Mortimer, A, Nelson, R, Clifton, A, & Renowden, S 2012, ‘Retained and fractured microcatheter: a cause of transient ischaemic attacks: endovascular management using carotid stents’, Interv. Neuroradiol, Vol. 18, no. 4, pp. 381–385. Oliva-Moreno, J, Aranda-Reneo, I, Vilaplana-Prieto, C, Gonz lez-Dom¡nguez, A, & Hidalgo-Vega, µlvaro 2013, ‘Economic valuation of informal care in cerebrovascular accident survivors in Spain’, BMC Health Serv. Res, Vol. 13, no. 508, pp. 1–15. Purroy, F, Suárez-Luis, I, Mauri-Capdevila, G, Cambray, S, Farré, J, Sanahuja, J, Piñol-Ripoll, G, Quílez, A, González-Mingot, C, Begué, R, Gil, M, Fernández, E, Benabdelhak, I 2014, ‘N-terminal pro-brain natriuretic peptide level determined at different times identifies transient ischaemic attack patients with atrial fibrillation’, Eur. J. Neurol, Vol. 21, no. 4, pp. 679–683. Purushothaman, S, Salmani, D, Prarthana, K, Gundappa Bandelkar, S, & Varghese, S 2014, ‘Study of ECG changes and its relation to mortality in cases of cerebrovascular accidents, J. Nat. Sci. Biol. Med, Vol. 5, no. 2, pp. 434–436. Santos, J, Hamadeh, Z, & Ansari, N 2012, ‘Cerebrovascular accident secondary to paradoxical embolism following arteriovenous graft thrombectomy’, Case Rep. Nephrol, pp. 1–3. Sharma, A, Sane, H, Nagrajan, A, Gokulchandran, N, Badhe, P, Paranjape, A, & Biju, H 2014, ‘Autologous bone marrow mononuclear cells in ischemic cerebrovascular accident paves way for neurorestoration: a case report’, Case Rep. Med, 2014, e530239. Srikanthan, A, Ethier, J.-L, Ocana, A, Seruga, B, Krzyzanowska, M, & Amir, E 2015, ‘Cardiovascular toxicity of multi-tyrosine kinase inhibitors in advanced solid tumors: a population-based observational study’, PLoS ONE, Vol. 10, no. 3, pp. 1–14. Timlin, H, & Petri, M, 2013, ‘Transient ischemic attack and stroke in systemic lupus erythematosus’, Lupus Vol. 22, no. 12, pp. 1251–1258 Van Rooij, F, Tuladhar, A, Kessels, R., Vermeer, S, Góraj, B, Koudstaal, P, Norris, D, de Leeuw, F, & van Dijk, E, 2015, ‘Cohort study on neuroimaging, etiology and cognitive consequences of transient neurological attacks (CONNECT): study rationale and protocol’, BMC Neurol, Vol. 15, no. 1, pp. 1–8. Read More