Atherosclerosis and Circulatory Physiology in the Coronary Arteries - Essay Example

How does atherosclerosis alter Normal circulatory physiology in the coronary arteries? MDM 135 Binoob Gopinath MSc Cardiology , Brighton Student No: 13844295 Date:02/02/2014 Word count:2500 Contents Introduction Page Question Page Literature Review Page Coronary Arteries and Normal Circulatory Physiology Page Inflammation process leading to atherosclerosis Page Coronary artery disease Page Conclusion Page References Page Appendix Page Abbreviations Page Introduction Atherosclerosis means the narrowing in the endothelium of the arterial wall can affect any arteries in the body .It can affect the arteries in the kidneys, brain, legs, heart, and pelvis1 resulting in various pathologies such as renal artery occlusions, carotid artery stenosis, peripheral and coronary artery disease. Coronary artery disease is a leading cause for deaths all over the world, even in the developed nations. According to NHS, cardiovascular disease causes about 124,000 deaths annually in Wales and England alone.3 Coronary atherosclerosis affects normal blood circulation by disruption of blood flow to the myocardium causing ischemia.4 The pumping ability of the heart get impaired when the myocardial ischemia occurs and failing to meet the metabolic needs of the heart. For the purpose of this essay, focus will be on the coronary artery disease. Literature Review I reviewed the medical literature and databases such as Pubmed, Google scholer and the journal databases for the Heart Rhythm Journal and Journal of American College of Cardiology (JACC), as well as the NICE and AHA websites for the state-of-the-art and latest guidelines updates . The following papers are used for the critical appraisal of my essay. Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease5 This paper reports on a recent study conducted to determine the effects of low and high coronary wall shear stress in the progression and transformation of atherosclerosis on patients suffering from coronary heart disease. The paper uses a good title that captures the overall purpose of the essay. The researchers confirm their hypothesis showing that low coronary wall shear stress develop greater plaque while high coronary shear stress leads to development of more severe calcium progression.5 These outcomes of this study are credible, as they where based on primary and secondary research methods. The researchers used relevant and credible literature to support their objectives and validate their findings. The results were analysed using statistical methods .As required of formal and credible research, main conclusions and study limitations where presented. Overall, this research paper presents points for the discussion in this essay. A tale of coronary artery disease and myocardial infarction6 This paper provides a comprehensive historical account of the developments made in medical research regarding coronary artery disease and its relationship with atherosclerosis. Throughout the paper, the authors, Nabel and Braunwald, present an objective review of literature citing the major developments since the 18th century. Specifically, how the inflammatory characteristics leading to atherosclerosis and plaque formation in the coronary arteries. They discuss about the progression of the plaque to form stenosis and coronary thrombosis and how these affect normal blood circulation in the coronary arteries.6 The authors are respectable researchers and specialists in cardiovascular diseases and have written other research papers on related matters. The essay provides credible and valid points for the discussion in this essay. Coronary Arteries and Normal Circulatory Physiology The coronary artery contains three main layers intima ,media and adventicia.Blood flow under normal physiology is unsteady. This is caused by the nature of the heart, which creates pulsatile conditions in the blood arteries. Due to the pulsatile conditions, the heart undergoes alternative cycles of diastole and systole to fill with blood or eject it to the blood vessels. The coronary arteries, reacts to changes in the physiological conditions in the cardiovascular system. Inflammation process leading to atherosclerosis The first event in the pathogenesis of the atherosclerosis is the injury to the intimal layer of the coronary artery13. The risk factors which can cause an injury to the intima are smoking, positive family history of Coronary artery disease, hypertension, dyslipidaemia, diabetes, psychological stress age, gender, obesity and lack of exercise, high calorie diet, high fat intake...23,24 etc. . Inflammation process in the endothelium is triggred by accumulation of tobacco toxin ,oxidised LDL23 ,Advanced glycation end products ,Elevated homocystiene . The inflammatory response to the plaques inside the coronary arteries is linked to the occurrence of selectins in the interior regions of the of the arteries. The principal function of the selectins is linked to the body immune response. The selections, especially the E-selectin and P-selectin, are responsible for recruiting leukocytes to the areas where the plaques have formed within the coronary arteries. Accumulation of Leucocytes ,T lymphocytes and primary monocytes move to the area of injury forming macrophages in the endothelium causing inflammation15. This leads to a change in the balance of production of endothelial-derived vasoactive molecules ;thus causing a decrease in bioavailability of endothelial nitric oxide which itself has an important role in vasodilator, anti-thrombotic and anti-proliferative properties. The oxidiced LDL in the endothelium are irritant which trigger releasing of proteins called cytokines.The cytokines present in the endothelium promote the adhesion attract the WBC especially monocyte.These monocytes embrace to the intimal layerand chane to macrophages into macrophages and starts swallowing the more oxidised LDL molecules. These macrophages gets overloaded with oxidized lipoprotein particles, the cholesterol foam cells.Some of thes cells die and release fat into inter cellular space attracts more macrophages.These form the fatty streak that is an early objective sign of atherosclerosis13. Chemokines are released by endothelial cells , attract monocytes and T cells to bind with activated endothelial cells, forming macrophages which in turn form the foam cells. The earliest lesion are known as ‘ fatty streaks’. Mechanical stretching and contraction of the artery, with each heart beat, i.e. the pulse, results in rupture of the thin covering membrane, spewing clot-promoting plaque contents into the blood stream.The clotting system reacts and forms clots both on the particles shed into the blood stream and locally over the rupture. If the clot is large enough,it might block the blood flow. This is due to the fact that all blood passes within seconds via five micrometre capillaries, and any unit larger than five micrometres has the capability to block the flow of blood. In any cases, the majority of clots and ruptures might be too diminutive to show symptoms. However, they have the propensity of induing damage to the heart muscle. For instance, slow but progressive heart damage might resulting to ischemic heart disease, which is one of the most universal form of congestive heart failure. The clot contracts within a period of time and leaves narrowing(s) known as stenosis. Cardiac arrest usually follows ruptures of vulnerable plaques of blood clots on found on the upper part of ruptured plaque which usually block theartery’s lumen stopping the flow of blood to necessary tissues. Moreover, atheroma rupture can cause bleeding from the lumen to get into the internal parts of the tissues suddenly increasing, as well as, protrusions into the lumen. This usually causes total obstruction or narrowing of the lumen. Imperative reflections of the theory above is shown in the IA precise nature, as well as, the events progression which might lead lipid retention. Several studies in experimental animals have demonstrated that lipid retention occurs before the monocytes migrate into the intima33, showing that the monocyte is not the cause of the lipid retention 33,34. It is important to note that the combination of inflammation with other forms of stresses, like high blood pressure might also cause splitting and spilling of the layer which covers the plaque in the blood stream. The inflammatory chemokines trigger the clotting mechanism of the body’s immune system, leading to the formation of coronary thrombus 10which eventually developed into fibrous plaque which with accumulation of further lipids lead to the formation of the fibrous cap. The Fibrous cap is made up of extra-cellular lipid, foam cells, T-tymphocytes, as well as, necrotic cellular debris. With time it evaluates into advance lesions(in adulthood) and eventually progresses into large plaque. Atheromata forms within the intima (innermost layer) of the coronary arteries causing their inflammation9. Within the atheromata, mast cells, T cells, as well as, macrophages infiltrate the lesion. Most of the immune cells produce inflammatory cytokines and show signs of activation. The continues infiltration of these cells within the atheromata leads to mycordial infarction, which occurs after normal blood flow within the coronary arteries is inhibited by the atheromatous process. 9 Large plaque is made of lipid that is soft and cholesterol rich atheromatous core. The external fibrous cap is made up of collagen and smooth muscle cells. Atherosclerosis plaque can remain stable for years without causing any symptoms Plaque rupture and thrombus formation Plaque rupture is a common event, and is usually asymptomatic. Vulnerable plaque are recognise by a large lipid pool(> 40% of overall plaque volume) , Low vascular smooth muscle cell in the cap ,High numbers of macrophages ,a thin fibrous cap Erosion of the endothelial layer and rupture of the overlying fibrous cap26 of the plaque exposes the highly thrombogenic lipid- rich core to the circulating blood. Collagen, tissue factors and other clotting factors mechanism activate the platelets and triggered platelets aggregation, producing a thrombus rich platelets10 and fibrin. The thrombus continue to grow and extend beyond the fibrous cap into the arterial lumen, causing arterial occlusion and leading to life threatening events like Acute Coronary Syndrome( ACS) and myocardial infarctions. The formation of plaque as a result of atherosclerosis is also associated with changing hemodynamic conditions within the arteries.26When the atherosclerotic plaque ruptures; this causes the formation of thrombus. The thrombus formation alters the hemodynamic conditions in the coronary arteries that prevent the arteries from performing normally. Without the normal hemodynamic conditions, the coronary arteries are not able to function normally in their task of supplying oxygenated blood to the heart. This leads to angina, ischemia , as well as, other cardiovascular ailments. The raptures of the Coronary plaque are usually responsible for about 75 percent of coronary thrombi, which leads to myocardial infarction as well as, death if an immediate response is not taken in terms of treatment. The presence of atherosclerosis also impairs normal responses of the coronary arteries to changes in the normal circulatory changes. The coronary arteries dilation is common and its usually related to alterations in blood pressure and its flow. However, atherosclerosis impairs this normal dilation response of the coronary arteries by causing endothelial dysfunction. The atherosclerosis affects the endothelium function in areas where the plaques form within the arteries. Dilation of coronary arteries is an imperative in its cardiovascular functions of the system. It helps in reducing shear pressure on the endothelial cells, which could lead to their dysfunction. Normal activities such as physical exercises and experiencing cold lead to dilation of the main coronary arteries in normal functioning of the coronary arteries.17 However, in the presence of stenosis ,the normal dilation of the coronary arteries will be disrupted17,18,19. The normal circulatory physiology in the coronary arteries is also affected by atherosclerosis through calcification.20 Coronary artery calcification is a common condition related with atherosclerosis.21 The plaque that forms as a result of atherosclerosis is partly comprised of calcium22. The link between atherosclerosis and inflammation in the coronary arteries is caused by the activation of immune response that leads to release of immune cells such as T-cell, dendritic cells, mast cells, and macrophages.15When this happens; the functioning of the arteries is hindered. The immune cells accumulate around the plaques formed by the presence of atherosclerosis. The ultimate outcome is that the coronary arteries no longer perform optimally. The presence of the plaques as well as the inflammation caused by the build-up of immune cells makes it difficult for the coronary arteries to carry blood to the heart normally. Rather than carry blood to the heart normally, the affected coronary arteries cannot carry enough blood to the heart. A stenosis represents the percentage of diameter reduction in the arteries. The formation and progression of stenosis often lead to pressure losses in the arteries, which hinders normal blood circulation. With a reduced pressure level due to the formation of stenosis, the coronary arteries are limited in their normal supply of blood to the heart.16 Additionally, the advancement of stenosis could lead to myocardial ischemia and coronary artery disease. The presence of stenosis within the arteries causes a contraction that leads to increased pressure of blood flow. However, this external pressure could exceed that of the internal fluid, which makes it easy for the artery to collapse.16The collapse of coronary arteries due to the constrictions caused by the presence of stenosis also hinders the normal circulatory physiology of these arteries. Conclusion From the discussion above, it has emerged that atherosclerosis is a major course of coronary heart disease. Atherosclerosis causes the formation of plaque within the coronary arteries which creates myocardial oxygen demand6 resulting in impairment of mechanical and electric activity of the heart. This partial or complete blockage of blood flow causes angina. It can affects normal circulatory physiology of the coronary arteries by the formation of thrombus7. The paque rupture and thrombus formation alters normal circulatory physiology by blocking the coronary arteries which leads to myocardial infarctions that could block the arteries completely or partially which could lead to death.An acute event can trigger fatal arrhythmias like ventricular tachycardia and ventricular fibrillation. The secondary effects of atherosclerosis are as follows.This could lead to longstanding ischeamic heart disease and ischemic cardiomyopathy.Ischemic cardiomyopathy will results in severely impaired left ventricular function and heart failure1. Myocardial infaction can result in scar and necrosis of the cells of the wall.This Scar tissue could trigget re-entrant ventricular arrhythmias which if not treated in time will be fatal. Although a lot still remains vague regarding atherosclerosis, 27various studies have provided evidence and insights to suggest that the disease affects the normal circulatory physiology in coronary arteries. So far, we can conclude that atherosclerosis affects coronary arteries by blocking them partially or completely, which prevents the normal flow of blood. References 1. Verônica Rolim SFC. Atherosclerosis imaging and heart failure. Heart Fail Rev 2006 12;11(4):279-88. 2. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature, 2011; 473(7347): 317-325. 3. American Medical Association (ASA). Autopsy-based study examines prevalence of atherosclerosis among U.S. service members. ScienceDaily. 2012 Dec 26 [accessed 14 January 2015]. Available from http://www.sciencedaily.com/releases/2012/12/121226080334.htm 4. NHS. Atherosclerosis. 2013 [accessed 14 January 2015]. Available from http://www.nhs.uk/conditions/atherosclerosis/Pages/Introduction.aspx 5. Samady H, Eshtehardi P, McDaniel MC, Suo J, Dhawan SS, Maynard C, et al. Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease. Circulation, 2011;124(7): 779-788. 6. Nabel EG, Braunwald E. A tale of coronary artery disease and myocardial infarction. New England Journal of Medicine, 2012;366(1): 54-63. 7. Lusis AJ. Atherosclerosis. Nature 2000 Sep 14;407(6801):233-41. 8. Farmer, JA, & Torre-Amione, G. Atherosclerosis and inflammation. Current atherosclerosis reports 2000;4(2): 92-98. 9. Hansson, GK. Inflammation, atherosclerosis, and coronary artery disease. New England Journal of Medicine 2005; 352: 1685-1695. 10. Madjid M, Vela D, Khalili-Tabrizi H, Casscells SW, Litovsky S. Systemic infections causes exaggerated local inflammation in the atherosclerotic coronary arteries. Tex Heart Inst J. 2007; 34(1): 11-18. 11. La Jolla Institute for Allergy and Immunology. Coronary artery disease research. 2008 [accessed 14 January 2015]. Available from http://www.liai.org/pages/coronary-artery-disease-research 12. Prescott SM, McIntyre TM, Zimmerman GA, et al. Molecular events in acute inflammation. Arterioscler Thromb Vasc Biol. 2002; 22: 727–733. 13. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999; 340: 115–126. 14. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002; 105: 1135–1143. 15. Hansson, GK. Immune mechanisms in atherosclerosis. Arteriosclerosos, Thrombosis, and Vascular Biology 2000 December;21(12): 1876-1890. 16. Ku D. BLOOD FLOW IN ARTERIES. Annual Review Of Fluid Mechanics [serial on the Internet]. (1997, Jan), [cited January 14, 2015]; 29(1): 399. Available from: Academic Search Complete. 17. Nabel EG, Ganz P, Gordon JB, Alexander RW, Selwyn AP:Dilation of normal and constriction of atherosclerotic coronary arteries caused by the cold pressor test. Circulation1988;77:43-52. 18. Golino P, Piscione F, Willerson JT, Cappelli-Bigazzi M, Focaccio A, Villari B, et al. Divergent Effects of Serotonin on Coronary-Artery Dimensions and Blood Flow in Patients with Coronary Atherosclerosis and Control Patients. N Engl J Med 1991 Mar 07;324(10):641-648. 19. Gage JE, Hess OM, Murakami T, Ritter M, Grimm J, Krayenbuehl HP: Vasoconstriction of stenotic coronary arteries during dynamic exercise in patients with classic angina pectoris: Reversibility by nitroglycerin. Circulation 1986;73:865-876 20. Wasilewski J, Niedziela J, Nowakowski A, Mirota K, Roleder M, Glowacki J, et al. OP-064 The Distribution of Coronary Artery Atherosclerosis Burden. The Impact of Septal Perforators on Plaque Localization at the Left Anterior Descending Artery; The Effect of Myocardial Bridging. Am J Cardiol 2014 Apr 01;113(7). 21. Patient.co.uk. Coronary artery calcium score. [Online]. 2012 [accessed 14 January 2015]; [1 screen]. Available from http://www.patient.co.uk/doctor/Coronary-Artery-Calcium-Score.htm 22. Lott S. Coronary artery calcium testing. [Online]. 2009, May 1 [accessed 14 January 2015]; [1 screen]. Available from http://www.insideradiology.com.au/pages/view.php?T_id=37#.VLY-jcmtFyw 23. Page IH, Stare FJ, Corcoran AC, Pollack H, Wilkinson CF. Atherosclerosis and the fact content of the diet. Circulation 1957, XVI: 161-178. 24. Braz DJ, Gutierrez PS, da Luz PL. Coronary fat content evaluated by morphometry in patients with severe atherosclerosis has no relation with serum lipid levels. Braz J Med Res 2007 April; 40(4): 467-473. 25. Pellizon, MA. Brief scientific literature review – diet-induced atherosclerosis/hypercholesterolemia in rodent models. [Online]. 2009 [accessed 14 January 2015]; [1 screen]. Available from:http://www.researchdiets.com/opensource-diets/diet-induced-disease-models/atherosclerosis 26. Westein, E, van der Meer AD, Kuijpers MJ, Frimat JP, van den Berg A, Heemskerk, JW. Atherosclerotic geometries exacerbate pathological thrombus formation poststenosis in a von Willebrand factor-dependent manner. Proceedings of the National Academy of Sciences, 2013; 110(4): 1357-1362. 27. Ravnskov, U, McCully, KS. Infections may be causal in the pathogenesis of atherosclerosis. The American journal of the medical sciences, 2012;344(5): 391-394. 28. Nabel EG, Selwyn AP, Ganz, P. Large coronary arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis. Journal of the American College of Cardiology 1990;16(2): 349-356. 29. Glagov S, Zarins C, Giddens DP, Ku DN. Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries. Archives of pathology & laboratory medicine 1988;112(10): 1018-1031. 30. Zeiher AM, Drexler H, Saurbier B, Just H. Endothelium-mediated coronary blood flow modulation in humans. Effects of age, atherosclerosis, hypercholesterolemia, and hypertension. Journal of Clinical Investigation 1993;92(2): 652. 31. Cox DA, Vita JA., Treasure CB, Fish RD, Alexander RW, Ganz P, Selwyn, AP. Atherosclerosis impairs flow-mediated dilation of coronary arteries in humans. Circulation, 1989;80(3): 458-465. 32. Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. British heart journal, 1983; 50(2): 127-134. 33. Packham MA, Rowsell HC, Jorgensen L, Mustard JF. Localized protein accumulation in the wall of the aorta.Exp Mol Pathol. 1967;7:214–232. [PubMed] Ross R, Fuster V: The pathogenesis of atherosclerosis: in Fuster V, Ross R, Topol EJ (eds): Atherosclerosis and coronary artery disease. Philadelphia - New York. Lippincott-Raven, 1996, vol 1, pp 441–462. 34. Nievelstein PFEM, Fogelman AM, Mottino G, Frank JS. Lipid accumulation in rabbit aortic intima 2 hours after bolus infusion of low density lipoprotein: A deep-etch and immunolocalization study of ultrarapidly frozen tissue.Arterioscler Thromb. 1991;11:1795–1805. [PubMed] Appendix : How I Conducted Literature Review I used various online databases and search engines for the articles that I used for literature review. The databases and search engines included: Google Search Google Scholar PubMed ProQuest EBSCO I used various statements, words, and questions to search for the literature. Some of these include: How does atherosclerosis cause inflammation of the coronary arteries? Atherosclerosis as an inflammatory disease Atherosclerosis Pathology of atherosclerosis Atherosclerosis and blood circulation Effect of atherosclerosis on normal circulatory physiology of the coronary arteries Read More