Atherosclerosis
- 1. GUIDED BY- Mrs. ANKITA S.V. Department of Life Science SUBMITTED BY- VIOLINA BHUYAN M.Sc I Semester Department of Life Science Bangalore University
- 2. CONTENTS INTRODUCTION DEFINATIONS CAUSES RISK FACTORS PATHOGENESIS ATHEROSCLEROSIS TIMELINE: Progression and morphology COMPLICATIONS AND SYMPTOMS EPIDEMIOLOGY DIAGNOSIS TREATMENT PREVENTIONS SUMMARY REFERENCES
- 3. DEFINATION Atherosclerosis is a condition where the arteries become narrowed and hardened due to plaque build-up around the artery. It is a chronic Inflammatory disease. Known as Arteriosclerotic Vascular Disease(ASVD).
- 4. INTRODUCTION Arteries carry blood from heart to the rest of the body. They are lined with a thin layer of cells called Endothelium. Endothelium keeps arteries smooth and mechanically elastic for easy flow of blood through them. Atherosclerosis starts with the damage of endothelium layer allowing harmful cholesterols to build inside the artery wall. Overtime, plaque builds up of all these cholesterols, WBCs, calcium salts and other substances and results in the narrowing of the lumen of the artery, obstructing the flow of blood.
- 6. CASES: 1. Plaque grows to a certain size and stops growing causing no problem to the individual. 2. The plaque clogs up the artery disrupting the flow of blood (can be cured with drugs and surgical interventions). 3. The plaque ruptures causing platelets to form thrombus. Blocks the artery completely leading to death of the individual due to stroke or heart attack.
- 8. CAUSES But all starts with the injury to the endothelium. “Injuries” may be caused due to- 1. Hyperlipidemia 2. Hypertension 3. Irritant as nicotine(from smoking) 4. Inflammatory cytokines 5. Diabetes 6. High cholesterol levels/obesity 7. Inflammation from diseases like Arthritis, Lupus and infections.
- 9. RISK FACTORS NON-MODIFIABLE FACTORS- 1. AGE: As the body ages, the risk for atherosclerosis increases. In men, risks increases after 45 years and in women, after 55 years of age. 2. GENDER: Male gender have higher risks of having atherosclerosis than female. Women are protected until menopause due to estrogen level in their body which increases antibody response to infections.
- 10. 3. FAMILY HISTORY: The risk for atherosclerosis increases if a father or brother was diagnosed with heart disease before 55 years of age or mother or sister before 65 years of age. 4. GENETIC ABNORMALITIES: -Familial Hypercholesterolemia. -Familial dysbetalipoproteinemia. -Inherited disorders of LDL metabolism.
- 11. MODIFIABLE FACTORS- 1. HYPERLIPIDEMIA. 2. HYPERTENSION. 3. DIABETES OR IMPAIRED GLUCOSE TOLERANCE (IGT) 4. TOBACCO SMOKING. 5. HYPERHOMOCYSTEINEMIA (elevation of homocystein). 6. ELEVATED SERUM-C REACTIVE PROTEIN (CRP) CONCENTRATION.
- 12. LESSER AND UNCERTAIN FACTORS- 1. Obesity- due to lifestyle, food habits,decreased HDL and increased LDL. 2. Type ‘A’ personality 3. High carbohydrate intake 4. Elevated serum levels of triglycerides, Lipoprotein concentration, Insulin, etc. 5. Elevated serum level of Uric acid
- 13. 6. Elevated fibrinogen concentration 7. Hyperthyroidism 8. Short sleep duration 9. Post menopausal- Estrogen deficiency (women) 10. Lack of physical activity 11. Chlamydia, pneumonia infections etc. 12. Alcohol consumption
- 14. PATHOGENESIS Atherosclerosis is a progressive disease that may begin as early as in childhood. Begins with fatty streak formation. Fatty streak is formed by accumulation of lipid laden foam cells in the Tunica intima of endothelium. Many hypothesis and theories were established to support the pathogenesis of the disease.
- 15. THEORIES: 1. Thrombogenic (encrustation) theory. 2. Insudation theory. 3. Monoclonal hypothesis. 4. Response-to-injury theory.
- 16. Out of all these theories, only Response-to-injury theory now has widespread acceptance. RESPONSE-TO-INJURY THEORY: Ross and Glomset,1972 Earliest event in Atherosclerosis is ‘Injury’ to the endothelium. According to the theory, ‘injury’ leads to endothelium dysfunction which increase vascular permeability of the endothelium to LDL and also allows platelet adhesion to the site. As a response to the ‘injury’, various inflammatory responses are provoked, WBCs are send to the rescue site, they get stuck in the plaque and finally the lumen starts narrowing.
- 17. STAGES INVOLVED IN ATHEROSCLEROSIS: The very first 2 stages of the disease is “endothelial injury” triggered by various causes and “endothelium dysfunction”.
- 18. PATHWAY AND MECHANISM OF PLAQUE FORMATION
- 19. ENDOTHELIUM “INJURY ENDOTHELIAL DYSFUNCTION RELEASE OF ROS INCREASE IN VASCULAR PERMEABILITY METALLO PROTEASE ALLOW LDL IN BLOOD TO ENTER IN TUNICA INTIMA OXIDIZES OXD. LDL RECEPTORS OF WBC AND T-CELLS MONOCYTES MACROPHAGE FOAM CELL ATTRACTS CHEMOKINESNECROSIS T-CELLS ENTERS PLAQUE AREA IFN-Y RELEASES LIPIDS PLAQUE RELEASES DNA ATTRACTS NEUTOPHILS SMC MIGRATION FROM MEDIA TO INTIMA INFLAMMATION IGF-1 SMC PROLIFICATION COLLAGEN MORE WBC PLAQUE GROWTH HARDENS PROTO INFLAMMATORY CYTOKINE + ROS
- 21. ATHEROSCLEROSIS TIMELINE: Progression and Morphology of Plaque development.
- 23. COMPLICATIONS AND SYMPTOMS Atherosclerosis can occur anywhere in the body including heart, legs, kidneys etc. Consequences/complications depends on the location of blocked arteries in the body. Though it begins its development early in the adolescence, but symptoms are not visible until an artery is narrow or clogged effectively . Atherosclerosis symptoms depends on which arteries it effects e.g., coronary, carotid, peripheral, renal or cerebrovascular arteries.
- 24. CORONARY ARTERY- blood vessels carrying blood and oxygen to the heart’s tissues. •Symptoms of Ischemic heart diseases. •Angina (chest pain) •Cardiac arrest •Arrhythmias •Fatigue CAROTID ARTERY- arteries present in neck and supplying blood to the brain. •Symptoms of stroke •Paralysis •Loss of consciousness •Sudden and severe headache •Sight trouble •Trouble speaking or understanding speech •Dizziness and trouble walking, loss of balance
- 25. PERIPHERAL ARTERY- these arteries provides blood and oxygen to legs, arms and other lower parts of the body. •Numbness of legs and arms •Loss of sensitivity •Pain during walking •Gangrene(tissue death) RENAL ARTERY- artery supplying blood and oxygen to the kidneys. •Tiredness •Duration of urination •Loss of appetite •Nausea •Swelling of hands and feet
- 26. ANEURYSMS- •Can occur anywhere in the body. •A bulge in the wall of an artery. If an aneurysm bursts, one may face life-threatening internal bleedings and deaths. •An sudden catastrophic event. •If a blood clots within an aneurysm, it may obstruct any artery at some distant point. CEREBROVASCULAR ARTERY- arteries in the brain causes permanent brain damages. •Symptoms of Transient Ischemic Attacks •Stroke without brain injury.
- 27. EPIDEMIOLOGY Atherosclerosis is a predominantly asymptomatic condition, due to which it is difficult to determine the incidence accurately. Atherosclerosis is less prevalent in Central and South America, Africa and Asia. More prevalent in U.S and Japan. According to U.S data for 2004, for about 65% of men and 47% of women, the first symptom of ACD is heart attack or sudden cardiac death.
- 28. • IHD and stroke are the world’s 1st and the 2nd cause of death respectively as given by WHO, for the year 2016. • In U.S, about 6,10,000 people die of IHD which accounts 1 out of every 6 deaths. • It has been reported that, 75% of acute myocardial infarctions occur from plaque rupture. • Stroke from any cause represents 2nd leading cause of death. • Nearly 7,35,000 people suffers from stroke every year in U.S resulting in 1,40,323 deaths.
- 29. EPIDEMIOLOGY OF INDIA : The Registrar General of India reported that CHD led to 17% of total deaths and 26% of adult deaths in 2001-2003. By 2010-2013, it increased in 23% of total and 32% of adult deaths. WHO and Global Burden of Disease study have highlighted increasing trends in CHD prevalence over the last 60 years. From 1% to 9-10% in urban population and from <1% to 4-6% in rural population.
- 30. DIAGNOSIS A diagnosis of atherosclerosis is based on – 1. Study of Family history. 2. Physical examination. 3. Test reports.
- 31. PHYSICAL EXAMINATION- Bruits(whooshing sound) over an artery. A weak or absent pulse bellow the narrowed areas of arteries. Signs of pulsating bulge (aneurysm). Decreased blood pressure in affected limbs or arms. Evidences of poor wound healing (areas where blood flow is restricted)
- 32. TEST REPORTS – Depending on the physical examinations, doctor suggests diagnostic test. Tests may include: 1. BLOOD TESTS : to check levels of fats, cholesterol, sugar, proteins etc in body which may increase the risk of atherosclerosis. 2. DOPPLER ULTRASOUND : Special ultrasound Measures blood pressures at various points along arm on legs. Uses sound waves. To gauge the degree of blockage and speed of blood flow.
- 33. 3. ELECTROCARDIOGRAM (ECG) : Simple, painless test that detects an records heart’s electrical activity. Shows the rhythm and speed of the heartbeats. Also shows signs of heart damage caused by CHD.
- 34. ANKLE-BRANCHIAL INDEX : Compares the blood pressure in the ankle with the blood pressure in the arm, calculating ankle-brachial index. Abnormal differences indicates PVD caused by atherosclerosis. ECHOCARDIOGRAPHY : Uses sound waves to create a moving image of your heart. Images identifies- -areas of poor blood flow to the heart -areas of muscles not contracting normally -previous heart injuries etc.
- 35. ANGIOGRAPHY: Inject special dye into the artery. The dye outlines narrow spots and blockages in the images.
- 36. OTHER TESTS: ADVANCED ULTRASOUNDS. MRA (MAGNETIC RESONANCE ANGIOGRAM) CT-SCAN (COMPUTED TOMOGRAPHY SCANS) These testes can show hardening and narrowing as well as aneurysms and calcium deposits in the artery wall.
- 37. TREATMENTS LIFESTYLE CHANGES. MEDICATIONS. SURGERIES.
- 38. 1. LIFESTYLE CHANGES – First line of defense in treating atherosclerosis. Eating healthy and balanced diet. Managing stress. Managing cholesterol, diabetes etc.
- 39. Exercising and maintaining body weight. Quitting smoking.
- 40. 2. MEDICATIONS – various drugs can slow or even reverse the effects of atherosclerosis. Cholesterol medications - Statins - Fibrates Anti-platelet medications - Aspirin (reduces likelihood of platelets to clump narrowed arteries) Anticoagulants – help thins blood to prevent clotting. - Heparin - Warfarins Blood pressure medications - Angiotensins - Beta blockers Diabetes medications.
- 41. 3. SURGERIES – surgeries may be recommended depending on the sverity of symptoms and extent of blockage. Endarterectomy : surgical removal of fatty deposits on walls. Bypass grafting : a graft bypass is created using a vessel from another part. Thrombolytic therapy : a clot in the artery is dissolved by inserting a clot dissolving drug into the artery. Angioplasty :
- 42. PREVENTIONS The same healthy lifestyle changes recommended to treat Atherosclerosis also help prevent it. PRIMARY PREVENTIONS – aims at either delaying atheroma formation or encourages regression of established lesions. 1. Quitting smoking and drinking. 2. Controlling hypertension, diabetes, cholesterol etc. 3. Weight loss. 4. Exercising and lowering total LDL level and increasing HDL.
- 43. SECONDARY PREVENTIONS - aims to prevent recurrence of events such as myocardial infarction or stroke in symptomatic patients. 1. Anticoagulants and Anti-platelet medications. 2. Cholesterol, diabetes or blood pressure medications. 3. Surgical interventions.
- 44. CONCLUSION Atherosclerosis is a Intima-based lesion organized into a fibrous cap and atheromatous core composed of SMCs, ECM, inflammatory cells, lipids and necrotic debris. It is driven by an interplay of inflammation and injury to artery walls. Plaques occurs slowly over decades and are clinically silent but may acutely cause symptoms due to rupture, thrombosis, hemorrhage etc. Atherosclerosis is a preventable and treatable condition.
- 45. REFERENCES Guyton, Arthur C. & John, E.2006.11th ed.,Textbook of Medical Physiology,Elsevier Saunders.1956,Pennsylvenia ref-10/10/19 nhlbi.nih.gov/health-topics/atherosclerosis. ref-8/10/19 ncbi.nlm.nih.gov/books/NBK507799/#targetText=Epidemiology ref-8/10/19 medical-clinical-reviews.imedpub.com/pathogenesis-of-atherosclerosis ref- 10/10/19 Sciencedirect.com/science/article/abs/pii/S0188440915001423 ref-8/10/19 Medicalnewstoday.com/articles/247837/php ref-8/10/19 Webmd.com/heart-disease/what-is-atherosclerosis#1 ref-10/10/19