Pathogenesis of Atherosclerosis - Coursework Example

Pathogenesis of Atherosclerosis Introduction Atherosclerosis refers to the process through which fatty substances, cellular waste, calcium, cholesterol, and fibrin accumulate in the endothelial lining of arteries. The accumulation of these products is referred as plaque. Atherosclerosis starts in the early years of teenage life, and it can develop for a period of 50years and beyond. The main causes of atherosclerosis are lipid retention, modification and oxidation stress. This factors lead to chronic inflammations on regions of vital conduit arteries. The pathogenesis of atherosclerosis is similar regardless of race, sex, and geographic location. Examples of Factors that increase the rate of atherosclerosis development include hypertension, diabetes mellitus, smoking, and obesity increases the rate. Atherosclerosis occurs asymptomatically, and its’ hallmark is the stoppage of blood flow to body regions served by affected vessels (Wick & Grundtman 2011, p.200). Early history of disease Atherosclerosis is a common medical condition characterized by stiffening of arteries. Several factors contribute to the hardening process, which include cholesterol, fat, immune factors, oxidative stress. Structures formed during atherosclerosis are referred to as plaques. These plaques are responsible for the blockage of affected arteries that may lead to serious medical complications such as stroke, high blood pressure, diabetes among other chronic medical conditions. Atherosclerosis occurs asymptomatically, which makes it difficult to take early medical interventions (Wick & Grundtman 2011, p.202). Hardening of arteries occurs as one ages. With aging, plaque develops gradually, causing the arteries to become narrow and stiffer. These changes make the flow of blood through arteries difficult. In some instances, clots may appear in the plaque affected vessels. Plaques may at times break off and cause a blockage in small blood vessels. Blockages from either the plaques or its breakages interfere with blood flow to body regions served by the affected arteries. This phenomenon deprives body organs of oxygen, which results to death of tissues. Presence of plaques in coronary arteries affects blood flow in the heart, which results to chest pain, shortness of breath, and finally a heart attack may occur leading to death (Hansson & Hermansson 2011, p.202). In the presence of a plague, two things are likely to occur. One bleeding may occur within the plaque; secondly, a thrombus may appear on the surface of the plaque. Atherosclerosis attacks medium sized and large arteries. However, the arteries attacked plus areas affected by the plaque vary with an individual. There are a number of theories that explain the pathogenesis of atherosclerosis, but many scientists are of the opinion that the condition is initiated by damage on endothelial cells of arteries. The three widely thought of causes of the endothelial damage include cigarette smoking, high blood pressure and increased levels of triglyceride and cholesterol in the blood (Chyu 2011, p.256). Presence of cigarette smoke speeds up the development of plaque in the aorta, coronary, and leg arteries. Damages on the arteries cause cholesterol, calcium, platelets, fat, and cellular debris to accumulate on arterial walls. Presence of these deposits may cause arterial cells to produce other harmful substances. Production of additional substances leads to accumulation of the inflammatory cells in the endothelial cells of the arteries. The accumulated cells continue to divide, and increased level of inflammatory cells creates a base where fat and other products build up. In addition, inflammatory cells create connective tissues. As this process continues, the endothelial cells get markedly thicker, which reduces the diameter of the affected artery (Wick & Grundtman 2011, p.206). In most cases, blood clots comprise the main cause of blockages in affected arteries. When these blockages are on coronary arteries, a heart attack may arise. Blockage on arteries that serve the brain with blood may lead to stroke while those on arteries that supply body extremities with blood may lead to gangrene. These three conditions are the most common in cases of atherosclerosis Adaptive and innate immune responses Atherosclerosis involves both the innate and adaptive immune responses. These components of the immune system are believed to cause modulating lesion initiation, disease progress, and subsequent devastating atherosclerosis complications. Research based evidence indicates that atherosclerotic plaques hold numerous components of the immune system. Examples of these components include T lymphocytes, dendritic cells, cytokines, immunoglobulin, complement, and B lymphocytes. Presence of these immune components serves as an evidence for the involvement of immune components in arthrogenesis. Studies on the involvement of adaptive and innate immunity in arthrogenesis have been done through knockout strategies (Hansson & Hermansson 2011, p203). Accumulation of immune components during the early stages of atherosclerosis suggests activated immune responses towards plaques are crucial in arthrogenesis. In regions where there are plaque ruptures, activated T cells, neutrophils, mast cells, and macrophages are in a high number. This is a significant evidence to show that the immune response plays a key role in later stages of atherosclerosis. As mentioned earlier, innate and adaptive immune responses are activated during arthrogenesis with an aim to clear foreign or altered self-agents. Despite the variation between the two arms of the immune system, there is a close communication between them, which leads to simultaneous activation of humoral and cellular immune responses (Hansson & Hermansson 2011, p.207). Immune responses are geared towards protecting the body against harmful agents, but during chronic inflammation of the endothelial cells making up the arteries, immune responses tend to be destructive. In such instances, there is aggravation of atherosclerosis, which may lead to plaque erosion (Smit & Hamsten 2012, p231). Oxidative stress Oxidation stress is believed to be one of the factors that trigger immune responses during atherosclerosis. Oxidative stress arises when there is a high level of free radicals. The cause of free radicals is the reaction between oxygen and certain biological molecules. This reaction initiates a series of reactions that cause damage on body tissues. The bulk of the available literature suggests that oxidized LDL (oxLDL) is responsible for triggering immune responses in atherosclerotic lesions. Accumulation of LDL on the endothelial cells of the arteries leads to oxidative modification of LDL (Chyu 2011, p257). After oxidation, LDL forms highly immunogenic neo-determinants products, which have the potential to trigger the adaptive and innate immune responses. In reference to innate immunity, it is evident that oxLDL can bind to a number of patter recognition receptors (PAMPS). In addition, animal and human observation studies indicate that oxLDL has the potential to activate the adaptive immune response (Chyu 2011, p261). Response to injury hypothesis There is numerous evidence, which supports the theory that atherosclerosis occurs as a result of damages on arterial endothelial cells. The theory supporting this idea is referred to as “response to injury hypothesis”. This hypothesis postulates that when endothelial cells of arteries suffer from injuries, the body responds by releasing a number of biological substances that lead to endothelial inflammation. According to this hypothesis, endothelial cells may get injured by oxLDL, raised plasma homocysteine, infectious microorganisms, and hypertension. In cases of endothelial inflammation, there is an increased rate of endothelial permeability to lipoproteins. Other changes include increased number of adhesion molecules, and enhanced growth factors. This two changes cause an increase in adherence of T lymphocytes, monocytes, and macrophages. These cells can penetrate through the endothelium to settle in the sub endothelial layer (Smit & Hamsten 2012, p.233). Macrophages within vascular walls sequester lipids to become large foam cells. The latter then produce growth factors and cytokines, which enhance the movement of smooth muscles. In addition, chemicals released from foam cells stimulate neointimal proliferation and their continued accumulation of lipids lead to endothelial cell dysfunction (Smit & Hamsten 2012, p.236). Infections Numerous infectious microorganisms have been thought to contribute to arthrogenesis. This is supported by the presence of infectious microorganisms in plaque material and seroepidemiological studies. These studies provide a correlation between atherosclerosis and pathogenic specific Abs. Most of the focus has been on Herpes viruses, C. pneumonia, H. pylori, and other oral pathogens. However, one thing not yet clear is whether these infectious microorganisms cause atherosclerosis. The other concern is whether the risk of atherosclerosis is increased by a single microorganism or a group of microorganism (Wick & Grundtman 2011, p.223). Of the mentioned microorganisms, C. pneumoniae is the most widely thought of the causative agent of atherosclerosis. Its presence in atherosclerotic plaque has been detected through various techniques, but its presence in normal arterial wall has been extremely rare. In addition, atherosclerotic lesions have demonstrated to contain T cells responding to C. pneumonia. This evidence suggests that the microorganism may be responsible for activating immune responses within the plaque. Less evidence supports the involvement of H. pylori in arthrogenesis. This is due to its absence in vascular tissues and blood stream (Wick & Grundtman 2011, p228). Attempts to isolate H. pylori from plaques are yet to give positive results. This makes it difficult to conclude on whether H. pylori has any role in arthrogenesis. Therefore, the only concrete evidence that is available to support the role of infectious microorganisms in arthrogenesis is that of C. pneumonia (Wick & Grundtman 2011, p230). Conclusion This paper has provided in details how atherosclerosis develops. It is clear that the condition is caused by a number of factors, but the hallmark of the whole process is the blockage of affected arteries. Arthrogenesis occurs gradually; in most cases, the condition develops asymptomatically; hence, it is difficult to note its development. In addition, the condition is irreversible once it has occurred, but there are medical interventions that help in its management. One crucial thing to note is that the immune system aggravates arthrogenesis in its attempt limit its development. References List Chyu, K.Y. (2011). Immune responce in Atherosclerosis and potential for an Atherosclerosis Vaccine. Discovery Medicine, 10(2), pp. 255-262. Hansson,K. & Hermansson,A. (2011). The immune system in atherosclerosis. PubMed, 12 (3), pp.204-12. Smit, A.& Hamsten, J. (2012). LDL oxidative modification and carotid atherosclerosis: Results of a multicenter study. Atherosclerosis, 225 (1) , pp.231-236. Wick, C. &Grundtman ,T. (2011). Inflammation and Atherosclerosis, London, Springer.pp. 200-232. Read More