You are here: start » group_1_presentation_1_-_global_burden_of_disease_cardiovascular_disease

Differences

This shows you the differences between two versions of the page.

--- group_1_presentation_1_-_global_burden_of_disease_cardiovascular_disease [2017/01/26 22:43]
kearneh
+++ group_1_presentation_1_-_global_burden_of_disease_cardiovascular_disease [2018/01/25 15:19] (current)
@@ Line 1: / Line 1: @@
-====== Global Burden of Disease: Coronary Artery Disease ======
+====== The Global Burden of Disease ======
+======History ======
+Ebola virus disease (EVD), also known as Ebola haemorrhagic fever, is a severe illness in humans.Ebola virus is a member of the viral family Filoviridae. It is a negative-sense, enveloped RNA virus with 7 genes (Toner et al., 2014). The Ebola outbreak in 2014 is due to the Zaire strain of ebola virus. The virus was first transmitted to humans from wild animals, and is now predominantly spread through the human population via human-to-human interaction. Mortality rate of the disease is 50%, with the first cases arising in Central Africa. Currently, there are no approved Ebola vaccines. Two potential vaccine candidates are undergoing research (Dixon & Schafer, 2014).
+{{ http://www.slate.com/content/dam/slate/articles/health_and_science/medical_examiner/2014/08/140805_MEDEX_EbolaUSA.jpg.CROP.promovar-mediumlarge.jpg }}
+**Figure 1:** The picture above shows the Ebola virus overlayed on a map of America. The picture represents the oncoming potential of the virus affecting individuals in America and causing mass deaths (Smith, 2014).
+====== Transmission ======
+Ebola virus can be transferred from an animal reservoir to humans. Bats are thought to be the reservoir species, with other intermediary hosts acting in between (Toner et al., 2014).
+The virus can be transferred to humans through contact with bodily secretions of infected wild wild animals, including; chimpanzees, gorillas, fruit bats, monkeys, forest antelope and porcupines found ill or dead in the rainforest (Dixon & Schafer, 2014). The ebola epidemic spreads widely mostly due to human-to-human contact of contaminated secretions. The virus is easily spread through traditional burial practises, where during the funeral the family would bathe, kiss, and embrace the body. Proper burial of bodies, and careful contact with infected patients is a vital asset in the prevention of the spread of ebola (Frieden et al., 2014).
+=== Fruit Bats and Ebola ===
+In 1976 the first ever reported cases of Ebola were reported, but the cause of this virus is still unknown. A group of scientists looked at a group of more than a thousand small vertebrates between 2001 to 2003 to look and collect samples of Ebola.  They looked in the areas of Gabon and the Republic of Congo, and found evidence of asymptomatic infection in three differing species of fruit bat. This could mean that the species could serve as a reservoir for the virus. Ebola outbreak in 2001 and 2005 were linked to analogous widespread deaths in gorilla and chimpanzee populations. To find the source of such infections 1,030 animals were captured, including 679 bats, 222 birds and 129 small terrestrial vertebrates. Of the infected species identified during these field collections, immunoglobulin G (IgG) specific for Ebola virus was detected in serum from three different bat species. The ebola virus specifically infected the liver and spleen of the animals, and the virus proliferated more rapidly in dry weather conditions (Leroy et al., 2005).
+====== Signs & Symptoms======
+{{ http://s29.postimg.org/4k7awqmw7/ebola_path.jpg }}
+**Figure 2:** The diagram explains how the symptoms express in a patient infected by the virus (Center of Disease Control, 2014).
+The symptoms of Ebola arise much like the common flu; with fever, fatigue, headache, sore throat and lethargic behaviour. The virus then moves into the gastrointestinal tract causing symptoms of vomiting, rash, impaired kidney and liver function and diarrhea.  The infection affects all organs until the patient gets septic shock and suffers organ failure.
+=== Symptom Timeline ===
+The following symptoms will occur in patients at varying rates dependent on immune function, and viral infection.
+__**1. Early Stage Symptoms:**__
+   * 0-5 days after incubation period
+   * fever, fatigue, malaise, anorexia, headache, hiccups, abdominal pain
+   * These symptoms can often be overlooked and diagnosed as influenza if clinician isn't aware of an Ebola outbreak.
+__**2. Mid-Stage Symptoms:**__
+  * Roughly after 5 days
+  * Severe watery diarrhea and vomiting
+__**3. Late Stage Symptoms:**__
+   * Bleeding from eyes
+   * Septic Shock
+   * Death
+(Toner et al., 2014)
+====== Pathogenesis ======
+The ebola virus (EV) first enters the  host through the mucous membranes, breaks in the skin (including microabrasions), or punctures (Toner et al., 2014). The virus attacks and replicates in a wide variety of host cells, but initially targets immune cells such as the monocytes and macrophages at the site of inoculation, as well as dendritic cells (Walker & Paessler, 2013). Infected immune cells are responsible for the spread of the virus from the site of inoculation to the rest of the body (Martines et al., 2014). Infected cells travel through the lymphatic system to the regional lymph nodes where they enter the bloodstream to the liver and spleen (Martines et al., 2014). If left untreated, the virus then spreads to the rest of the body and is present in the skin and in all body fluids. The virus can thus cause cellular damage and leads to necrosis of many different organs.
+The infection of human monocytes with ebola results in the activation of monocytes and increased release of pro-inflammatory cytokines and chemokines. The inflammation damages blood vessels, and causes leakage and internal bleeding of the host. Infected dendritic cells and macrophages result in impairment of T-cell maturation and proliferation, and thus compromises host immune system (Walker & Paessler, 2013). Additionally, the presence of ebola virus glycoproteins (GP) found on the transmembrane of the viral structure causes cell damage, and alters the release of cytokines important to inflammation and fever response. Additionally, the virus affects endothelial cells and causes damage to vascular integrity.
+{{http://www.nature.com/nri/journal/v7/n7/images/nri2098-f1.jpg}}
+**Figure 3**: The pathogenesis of ebola virus. Initial entry into hostleads to increased inflammation, decreased immune response, damage to vasculature, and necrosis of different organs (Geisbert et al., 2003).
+The onset of symptoms upon infection ranges between 2 to 21 days. An individual is not infectious until symptoms are shown. Laboratory tests will indicate high white blood cell and platelet counts and elevated liver enzymes.It is believed that that the Ebola virus works through glycoproteins found on the transmembrane of the structure. When the glycoprotein (GP) introduces its contents into monocytes or macrophages it causes cell damage that alters the release of cytokines important to inflammation and fever response, as well as affecting endothelial cells, causing damage to vascular integrity (Geisbert et al., 2003). The other glycoprotein released by the Ebola virus, sGP, may affect the human immune response by inhibiting neutrophil activation. The transmembrane GP may contribute the symptoms of hemorrhagic fever by localizing the virus to cells of the reticuloendothelial network and the lining of blood vessels (Frieden et al., 2014).
+====== Biochemistry ======
+The ebola virus is covered in an glycoprotein envelope which allows the virus to bind to the host cell membrane and infect the cell.  Within the envelope is the virus’ genome which consists of seven genes which are responsible for the production of proteins in transcriptional editing.  Another protein termed sGP is responsible for the early stages of the infection. Its serves only as a structural protein and it does not adhere to the surface of the cell. The second protein, GP, contains a hydrophobic tail, and is present on the surface of the envelope, making it responsible for the infection of new cells.  The human immune system works in preference of sGP over the GP protein. The goal of vaccine therapy is to create an antibody that targets the GP while ignoring sGP.
+ Chemists have been better able to understand the structure of the virus to X-ray crystallography. GP is composed of 676 amino acids broken up into two sections by a cysteine disulphide bond. The first section is responsible for attachment to the host cell. The second subsection integrates the viral envelope into the host cell membrane. The most promising method for disrupting the virus life cycle involves the creation antibody that targets GP1 or GP2 (Geisbert et al., 2003).
+{{ http://jvi.asm.org/content/77/18/9733/F1.medium.gif }}
+**Figure 4:** The above diagram explains how glycoproteins found on the nuclear envelope of the virus cells attack macrophages. Once they attack macrophages, cytokines are leased that caused endothelial cell toxicity (Geisbert et al., 2003).
+====== Treatments ======
+Rehydration with oral or IV fluids and treatment of specific symptoms improves chances of survival in symptomatic patients. Although there is no cure available for EVD, an arrange of potential treatments including blood products, immune therapies and drug therapies are currently being evaluated (Sullivan et al., 2000). The new treatments target the Zaire Ebola Virus Strain (ZEBOV), the strain observed in the current outbreak (Zeliadt, 2014). With over 50 million dollars in funding from the US National Institutes of Health, Thomas Geisbert’s lab at the University of Texas is conducting a big portion of this research along with scientists in Baltimore, Maryland and Canada’s Tekmira pharmaceuticals (Zeliadt, 2014).
+===== rVSV-ZEBOV Vaccine =====
+This vaccine is being developed in Geisbert’s lab by using a recombinant vesicular stomatitis virus (rVSV). The vector expresses the Ebola glycoprotein in order to create immunity in rhesus macaques (Geisbert & Feldmann, 2011). Trials performed on macaque monkeys have shown that a single shot of the vaccine is enough to save them from a lethal dose of the virus (Meltzer et al., 2014). These observations were made twenty-eight days post infection (Geisbert & Feldmann, 2011). Furthermore, the vaccine has been shown to be effective when administered half an hour post infection (Geisbert & Feldmann, 2011). This vaccine is currently undergoing phase 1-safety trials in humans (Meltzer et al., 2014).
+===== ZMapp "Antibody Cocktail" =====
+The newest treatment being developed in Geisbert’s lab is ZMapp. ZMapp is a monoclonal-antibody therapy consisting of the three monoclonal antibodies: c13C6, c2G4, and c4G7 (Qiu et al., 2014). Trials done on rhesus macaque monkeys have shown that ZMapp is effective in protecting macaque monkeys from a lethal dose of Ebola virus, with treatment starting as late as five days post infection (Qiu et al., 2014). When therapy was initiated, fever, leukocytosis, thrombocytopenia and viraemia were present in the majority of monkeys (Qiu et al., 2014). These symptoms and other physiological abnormalities were reversed and virus load was lowered after initiation of therapy (Qiu et al., 2014). The monkeys made a full recovery twenty-eight days after infection. However, it is unknown if ZMapp-treated survivors of Ebola are prone to reinfection (Qiu et al., 2014).
+Recently, ZMapp was used compassionately for two American healthcare workers, Dr. Kent Brantly and Nancy Writebol, who were infected with Ebola virus (University of Texas, 2014). Overall, the two individuals responded well and are now virus-free (University of Texas, 2014). However, the efficiency of this therapy remains unknown as 45% of Ebola patients make a recovery without treatment (University of Texas, 2014).
+===== TKM-Ebola Drug =====
+This drug was developed by Canada’s Tekmira pharmaceuticals along with the Geisbert lab (Zeliadt, 2014). It involves RNA interference (RNAi) by targeting ZEBOV genes and silencing them (Zeliadt, 2014). The drug was observed to protect rhesus macaques from lethal doses of the Ebola virus; as long as it is administered within two days post infection (Zeliadt, 2014). It is now being tested in phase 1-safety human trials along with combinations of ZMapp and other antibodies. As the FDA continues to allow its development, TKM-Ebola may provide insights into the role of epigenetics in the Ebola outbreak (Zeliadt, 2014).
+===== ChAd3 Vaccine =====
+Human derived adenovirus has been used as a vector to develop vaccines for several pathogenic diseases (Stanley et al., 2014). In fact, a vaccine using the human derived adenovirus type 5 vector (rAd5) has been observed to protect macaque monkeys against ZEBOV (Stanley et al., 2014). However the main limitation to human derived adenovirus vectors is pre-existing immunity to the vector due to previous exposure in the environment (Stanley et al., 2014).
+In affiliation with the University of Texas, Nancy J. Sullivan of the National Institute of Allergy and Infectious Diseases Vaccine Research Center has developed a vaccine that uses a chimpanzee derived adenovirus type 3 vector (NIH, 2014). The vector expresses the Ebola glycoprotein in order to trigger an immune response in macaque monkeys (Stanley et al., 2014). Only two of the four macaques that were vaccinated were able to survive when given lethal doses of the ZEBOV ten months following immunization (Stanley et al., 2014). However, when a booster shot was provided eight weeks post initial vaccination, all four macaques survived when the ZEBOV was introduced ten months later (NIH, 2014). The booster shot was created from a different vector, a poxvirus, with Ebola glycoprotein expression (Stanley et al., 2014). This research suggests that CD8+ T-cells (also known as Killer T cells) as well as memory T cells are needed in high quantities so that the immune system can clear the virus from the host (Stanley et al., 2014). This vaccine is currently in phase 1-safety trials in Maryland (NIH, 2014).
+====== Ebola World Wide ======
+===== Ebola In Canada =====
+Recently, it has been reported that the Health Science Department in Hamilton, Ontario will be an institution accepting individuals that could potentially have Ebola. They have provided a list of things that will be used. These involve:
+   * Hand sanitizer
+   * Equipment that covers the foot and extends to the knee
+   * Gown (prevents needles from entering)
+   * n95 mask(air filter)
+   * gloves
+At the end of this process, another person will ensure there aren’t any openings (CHCH news, 2014).
+Individuals in Hamilton should not worry. One of the reasons is that an individual doesn’t get Ebola that quickly from another person. It requires very close association with another person’s bodily fluids. Moreover, there aren’t flights heading from West Africa to Canada. Hence, this drastically decreases the possibility of Ebola coming to Canada. In addition, it does put fear in people since there isn’t a cure for it. There have been approximately 20 potential Ebola cases but they have all been negative (Carter, 2014).
+===== Ebola In Nigeria =====
+An individual named Sawyer arrived to Nigeria on July 20th. Sawyer was extremely ill and had recently come back from his sister’s funeral in Liberia. Sawyer was taken to the hospital and he past away (Macharia, 2014).
+The steps taken that allowed Nigeria to contain Ebola from spreading rapidly:
+Firstly, there was immediate documentation: Sawyer was the first individual to be diagnosed with Ebola and was taken to the hospital immediately.
+Secondly, there was excellent support from the government. Was able to provide the necessary resources such as funds to solve the situation.
+Thirdly, the virology laboratory equipment is advanced which allows determination of potential Ebola situations much easier.
+Fourthly, the campaigns are effective.
+Lastly, they were able to determine the 20 individuals and families that came into contact with Sawyer at the Hospital. In addition, they concluded that there was about 898 individuals that the 20 people came into contact. They were all checked for symptoms regarding Ebola for a period of 21 days (Macharia, 2014).
+====== Prevention ======
+Ebola is a very contagious and deadly disease. The best way to prevent infection is to avoid contact with sick individuals and avoid handling human remains of sick individuals. Additionally, avoid areas with known outbreaks. Wash hands frequently to avoid spread and infection of ebola. Avoid bush meat in specific areas of Africa.  Most importantly, when in contact with individuals who are infected, follow CDC protocol for infection control (Meltzer et al., 2014).
+======Conclusion======
+The CDC is predicting 1.2 million Ebola cases by January 2015. However, the recent eradication of Ebola in Nigeria gives hope that, when proper preventative and control measures are taken, Ebola can be contained and the outbreak can be brought to an end. Worldwide efforts are needed in order to stop the spread of Ebola to other countries. Financial and healthcare support needs to continue to be sent to areas currently dealing with outbreaks. Initial control efforts in certain regions were hindered because there was disbelief that an Ebola outbreak was real and something to be concerned about. To ensure that citizens are willing to comply with and join control measures issued by governments and health agencies, we all need to be spreading awareness of the significance of Ebola but at the same time prevent unnecessary anxiety and false information from being passed on. Regardless of where you live, by everyone knowing how to recognize the signs of Ebola and what to do in case of an outbreak would greatly reduce the chance of an Ebola in other parts of the world. Humanity needs to join together and we all need to do what we can to help those who are effected and prevent others from being effected (Toner et al., 2014).
-{{:crohn_s_disease_cd_.pdf|}}
 ===== Introduction =====
@@ Line 14: / Line 145: @@
 http://www.nhlbi.nih.gov/health/health-topics/topics/copd>
-<box width classes round white centre|>{{:12021.png|}}</box| Figure 1: Inflammation of the Gastrointestinal (GI) Tract>
+<style float-right>
+{{:messages_image_207363904_.png|}}
-**Epidemiology**
+<style float-right>
+{{:screen_shot_2016-09-21_at_12.40.17_pm.png|}}
+</style>
-According to a National Survey analysis that was done on a geographically diverse health insurance claims database, it estimated that the prevalence of Crohn disease among US children and adults between 2003-2004 to be 201 cases per 100,000 persons among adults and 43 per 100,000 among children.
+**Coronary Artery Disease**
-Urban areas are estimated to have a higher prevalence of IBD than rural areas do. Moreover, upper socioeconomic classes are predicted to have a higher prevalence than lower socioeconomic classes due to the difference in the access to health care between the two groups.
+Coronary Artery disease (CAD), also known as Coronary Heart Disease (CHD) and Ischaemic heart disease is the largest contributor to cardiovascular diseases (Wong 2014). The diseases are characterized by: angina (chest pain), shortness of breath and myocardial infarction which may contribute to patient mortality. One of the main causes of CAD is atherosclerosis which is characterized by gradual thickening of the coronary artery walls. This occurs when plaque, composed of debris, fat and organic substances accumulates inside the arterial walls, leading to narrowing and hardening of the blood vessels.
-In general, the frequency of this disease is similar in males and females, with some studies that shows a very slight female predominance. The rate of Crohn disease is deemed to be 1.1 – 1.8 times higher in women than in men. Moreover, Crohn disease is reported to be more common in white patients than black patients, and very rare in Asian and Hispanic individuals. On average, approximately 20% of all Crohn disease patients are of black descent.
+Other risk factors include hypertension, cigarette smoking, diabetes mellitus or elevated glucose levels, increased cholesterol levels, and obesity (Wong, 2014). Specifically, a dangerous combination of poor nutrition and lack of physical exertion can lead to many of these risk factors. Current research suggests preventive measures are the most beneficial in reducing an individual's risk for developing CAD; this includes proper nutrition and doing regular exercise. Furthermore, additional treatment options include the use of medication such as beta blockers, nitrates, angiotensin converting enzyme (ACE) inhibitors, and antiplatelets. Surgery is a more invasive option for those afflicted with multiple blockages and the goal is to improve circulation of blood towards the heart.
+<box width classes round white centre|>{{:12022.png|}}</box| Figure 2: Invasion of granulosa cells inducing inflammation in GI tract.>
+==== Epidemiology ====
+CAD is a major cause of death and disability in developed countries, although mortality rates have been observed to be decreasing over the last decades in western countries (Sanchis-Gomar et al 2016). Despite the decline, CAD still causes approximately one-third of all deaths in people older than 35 years. The Framingham Heart, which is an ongoing population-based cardiovascular cohort study concludes the many risk factors that contribute to CAD. The study concluded that men over the age of 38 had 1.5 times greater risk of developing atrial fibrillation than women (Benjamin et al 1994). A follow up of the Framingham study based on 44 years of data and observation of the offspring of the original study members was conducted. Results indicated individuals aged over 40, the lifetime risk of developing CAD was 49% in men and 32% in women. The lifetime risk for 70 years old individuals was 35% in men and 24% in women. Lastly, for total coronary events, the incidence rose steeply with age, with women behind men by approximately 10 years.
+The 2016 Heart Disease and Stroke Statistics update of the American Heart Association reported that 15.5 million people over 20 years of age in the USA have CAD, with the prevalence increasing with age for both sexes (Sanchis-Gomar et al, 2016). The results of the data collected on CAD and MI is illustrated in the graphs where the prevalence for men is observed to be much greater than women. Furthermore, in a 2009 report based on data from National Health and Nutritional Survey (NHANES), myocardial infarction prevalence was observed in middle aged individual (35-45 years of age) during the 1988-1994 and 1999-2004 time periods. The results indicated a higher prevalence in men compared to women, but the trend declined for the former over time.
+The World Health Organization released estimates of the global and regional burden of disease, which included 20 leading causes.The data was collected for 2000 and 2012, with a reported increase in DALY being observed both globally and in regions such as Southeast Asia, the Eastern Mediterranean and the western pacific region. The global rank of ischemic heart disease increased from being the third leading cause of death in 2000 to the first leading cause of death in 2012 (World Health Organization, n.d.) Although the global burden of coronary artery disease was dominant in western countries during the early 20th century, the burden now lies in specific Asian and middle-Eastern regions (Wong 2014). The global ischemic heart disease DALY data collected for both sexes indicates a high concentration in central asia, North Africa and West Europe.
@@ Line 34: / Line 179: @@
 **Coronary Artery Anatomy**
-Arteries are shaped like hollow tubes and have muscular walls lined with a layer of cells known as the endothelium. These walls are smooth and elastic and provide a physical barrier between the walls of the artery and the blood stream.
+Arteries are shaped like hollow tubes and have muscular walls lined with a layer of cells known as the endothelium (Libby & Theroux, 2005). These walls are smooth and elastic and provide a physical barrier between the walls of the artery and the blood stream (Cleveland Clinic, 2017).
+<box width classes round white centre|>{{:AA.png|}}</box| Figure 2: Anatomy of a Coronary Atery.>
 **Atherosclerosis**
-One of the leading causes of CAD is atherosclerosis or the gradual thickening of the walls of the coronary arteries. Atherosclerosis occurs when plaque builds up inside of arterial walls, causing the narrowing and hardening of these blood vessels.
-As individuals age, cellular debris begins to stick to the vessel walls. The amalgamation of debris, fat and other substances combine to create what is known as ‘plaque.' Plaque can be composed of many things, but often includes cholesterol, fat substances, metabolic waste, calcium, and fibrin (a clotting compound found in the blood). The inside of the arteries develop plaques of different shapes and composition as a person ages. Most plaques have a fibrous ‘cap’ covering a softer interior. If the cap either cracks or is torn, the soft inside is exposed, and platelets form a clot around the plaque. This can cause irritation in the endothelium, and even cause a disruption in function where the artery contracts inappropriately and thus narrows the artery even more.
+One of the leading causes of CAD is atherosclerosis or the gradual thickening of the walls of the coronary arteries (Cleveland Clinic, 2017). Atherosclerosis occurs when plaque builds up inside of arterial walls, causing the narrowing and hardening of these blood vessels (Cleveland Clinic, 2017).
-Once broken off, the clot may disintegrate into smaller components, thus restoring normal blood flow patterns. However, what often happens is the thrombus (blood clot) begins to block blood supply to the heart muscle causing what is known as a coronary occlusion. This would be an acute cause of CAD, as it is the result of a sudden rupture of a plaque and formation of a thrombus. The alternate cause of CAD is of chronic origin- the coronary artery is simply narrowed over time and blood supply is slowly limited.
+As individuals age, cellular debris begins to stick to the vessel walls. The amalgamation of debris, fat and other substances combine to create what is known as ‘plaque' (Libby & Theroux, 2005). Plaque can be composed of many things, but often includes cholesterol, fat substances, metabolic waste, calcium, and fibrin (a clotting compound found in the blood) (Libby & Theroux, 2005). The inside of the arteries develop plaques of different shapes and composition as a person ages (Libby & Theroux, 2005). Most plaques have a fibrous ‘cap’ covering a softer interior. If the cap either cracks or is torn, the soft inside is exposed, and platelets form a clot around the plaque (Cleveland Clinic, 2017). This can cause irritation in the endothelium, and even cause a disruption in function where the artery contracts inappropriately and thus narrows the artery even more (Cleveland Clinic, 2017).
+Once broken off, the clot may disintegrate into smaller components, thus restoring normal blood flow patterns (Cleveland Clinic, 2017). However, what often happens is the thrombus (blood clot) begins to block blood supply to the heart muscle causing what is known as a coronary occlusion. This would be an acute cause of CAD, as it is the result of a sudden rupture of a plaque and formation of a thrombus (Cleveland Clinic, 2017). The alternate cause of CAD is of chronic origin- the coronary artery is simply narrowed over time and blood supply is slowly limited (Cleveland Clinic, 2017).
 **Atherosclerotic Lesions**
-Beginning as smaller lesions, early atherosclerotic lesions can then rapidly enlarge into plaques in individuals with coronary risk factors. Atherosclerotic lesions, or atheromata, are the asymmetric thickening of the intima (the innermost layer of the artery). Atheromata are composed of cells, connective tissue elements, lipids, and cellular debris. The core of an atheroma is made up of immune cells such as T-cells and macrophages, which can produce inflammatory cytokines, coagulation factors, radicals, and proteases when activated. These factors can then, in turn, destabilize lesions and induce ischemic events.
+Beginning as smaller lesions, early atherosclerotic lesions can then rapidly enlarge into plaques in individuals with coronary risk factors (Fuster et al., 1992). Atherosclerotic lesions, or atheromata, are the asymmetric thickening of the intima (the innermost layer of the artery). Atheromata are composed of cells, connective tissue elements, lipids, and cellular debris (Fuster et al., 1992). The core of an atheroma is made up of immune cells such as T-cells and macrophages, which can produce inflammatory cytokines, coagulation factors, radicals, and proteases when activated. These factors can then, in turn, destabilize lesions and induce ischemic events (Fuster et al., 1992).
+<box width classes round white centre|>{{:AB.png|}}</box| Figure 3: Stable vs. Unstable Atherosclerotic Lesions>
 **Ischemic Events & Plaque Disruption**
-An ischemic event occurs when there is a restriction or a reduction in blood supply to the tissues, causing a shortage in the materials needed for cellular metabolism in the cells (e.g. oxygen and glucose). In CAD, there are a variety of ways in which ischemic events can be triggered.
-) Lipid-Rich Plaques - Small atherosclerotic plaques are often made up of a crescent-shaped mass of lipids, and are relatively small and soft due to both their high concentration of cholesterol and the presence of the chemical compound ester. If there is a change in shear force around the area of stenosis or a sudden change of intraluminal pressure, these small plaques may be disrupted and cause an ischemic event.
+An ischemic event occurs when there is a restriction or a reduction in blood supply to the tissues, causing a shortage in the materials needed for cellular metabolism in the cells (e.g. oxygen and glucose) (Fuster et al., 1992). In CAD, there are a variety of ways in which ischemic events can be triggered (Fuster et al., 1992).
-) Macrophages - Responsible for the uptake and metabolism of lipids, macrophages are thought to play a role in the development of plaques. Macrophages may also play a role in plaque formation because they enhance the transport of cholesterol, and release a mitogenic factor that helps the proliferation of smooth-muscle cells. They play a role in plaque disruption as they release proteases that digest the extracellular matrix, which can then cause a plaque to be released.
-) Vessel Wall Stress - Plaques may also be disrupted due to alterations on or within plaques. Some plaques, known as fissured plaques, contain a fibrous cap that when under tensile stress, can rupture due to the lack of collagen support under the cap. Other forms of plaques may be distressed by vessel wall stress due to the disturbed blood flow pattern due to areas of stenosis (narrowing). This altered pressure and flow may cause plaque tearing. Finally, plaques may also be disrupted by the bending and twisting of the artery during contractions.
+) Lipid-Rich Plaques - Small atherosclerotic plaques are often made up of a crescent-shaped mass of lipids, and are relatively small and soft due to both their high concentration of cholesterol and the presence of the chemical compound ester. If there is a change in shear force around the area of stenosis or a sudden change of intraluminal pressure, these small plaques may be disrupted and cause an ischemic event (Fuster et al., 1992).
+) Macrophages - Responsible for the uptake and metabolism of lipids, macrophages are thought to play a role in the development of plaques. Macrophages may also play a role in plaque formation because they enhance the transport of cholesterol, and release a mitogenic factor that helps the proliferation of smooth-muscle cells. They play a role in plaque disruption as they release proteases that digest the extracellular matrix, which can then cause a plaque to be released (Fuster et al., 1992).
+) Vessel Wall Stress - Plaques may also be disrupted due to alterations on or within plaques. Some plaques, known as fissured plaques, contain a fibrous cap that when under tensile stress, can rupture due to the lack of collagen support under the cap. Other forms of plaques may be distressed by vessel wall stress due to the disturbed blood flow pattern due to areas of stenosis (narrowing). This altered pressure and flow may cause plaque tearing. Finally, plaques may also be disrupted by the bending and twisting of the artery during contractions (Fuster et al., 1992).
 **Symptoms**
 CAD can present itself in a variety of ways, including:
-) Chest Pain (Angina) is typically described as tightness or pressure in your chest and normally occurs in the middle or left side. Typically induced by stress, the pain usually subsides within minutes of reducing exertion. Women tend to feel the pain in the neck, arm, or back instead of the chest.
-) Shortness of Breath  is due to the obstruction or stenosis of arteries. In these cases, the heart is unable to pump blood to meet the needs of the body which can cause extreme fatigue.
+) Chest Pain (Angina) is typically described as tightness or pressure in your chest and normally occurs in the middle or left side. Typically induced by stress, the pain usually subsides within minutes of reducing exertion. Women tend to feel the pain in the neck, arm, or back instead of the chest (Mayo Clinic Staff, 2015).
+) Shortness of Breath  is due to the obstruction or stenosis of arteries. In these cases, the heart is unable to pump blood to meet the needs of the body which can cause extreme fatigue (Mayo Clinic Staff, 2015).
+) Heart Attack or Myocardial Infarction (MI) can occur if the coronary artery is completely occluded. Symptoms of a heart attack include a crushing or squeezing pressure in the chest, pain in your shoulder or arm, shortness of breath, nausea, denial, or sweating. Women often experience different symptoms than men, such as pain in the neck or jaw. Heart attacks can also occur without any of the hallmark warning signs or symptoms, these are known as ‘silent Heart Attacks’ (Mayo Clinic Staff, 2015).
-) Heart Attack or Myocardial Infarction (MI) can occur if the coronary artery is completely occluded. Symptoms of a heart attack include a crushing or squeezing pressure in the chest, pain in your shoulder or arm, shortness of breath, nausea, denial, or sweating. Women often experience different symptoms than men, such as pain in the neck or jaw. Heart attacks can also occur without any of the hallmark warning signs or symptoms, these are known as ‘silent Heart Attacks’.
 ===== Risk Factors =====
@@ Line 239: / Line 400: @@
 World Health Organization (n.d.). 50 Facts: Global health situation and trends 1955-2025. Retrieved from: http://www.who.int/whr/1998/media_centre/50facts/en/

Differences

Search

Navigation

Print/export

Tools

QR Code