ATHEROSCLEROSIS
SCHOOL OF VETERINARY MEDICINE-UB
The Heart
Is a muscle about the size of your fist Weighs approximately one pound Is located behind and slightly to the left of the breastbone Pumps about 5 quarts (4.7 liters) of blood every minute
The function of the heart is to circulate blood throughout the body by:
Pumping blood through the lungs removes carbon dioxide and refreshes the blood with oxygen The oxygenated blood is pumped to the body to provide oxygen and nutrients and to remove waste products. The coronary arteries are the blood vessels that supply blood and oxygen to the heart muscle.
Blood Supply To The Heart
2 coronary arteries branch from the main aorta just above the aortic valve. No larger than drinking straws, they divide and encircle the heart to cover its surface with a lacy network that reminded physicians of a slightly crooked crown (coronary comes from the Latin coronarius, belonging to a crown or wreath). They carry out about 130 gallons of blood through the heart muscle daily. (Clark, 119)
Coronary Artery Disease
Coronary artery disease is one of the most common and serious effects of aging. Fatty deposits build up in blood vessel walls and narrow the passageway for the movement of blood. The resulting condition, called atherosclerosis often leads to eventual blockage of the coronary arteries and a heart attack.
Pendahuluan
Seperti halnya di AS, saat ini PJPD menjadi penyebab kematian no.1 di Indonesia (Ulfah, 2000; diakses 2005). PJK merupakan penyebab kematian terbesar di banyak negara di dunia. Angka kejadian di Indonesia terus meningkat (Ulfah, 2000; diakses 2005). SKRTN 1972: PJK urutan ke-11 SKRTN 1986, menjadi urutan ke-3 SKRTN 1992, menjadi ururan ke-1: 16% kematian SKRTN 1995, meningkat: 18,9 % kematian SKRTN 2001, meningkat: 26,4 % kematian (Sibarani, 2003) > separo kematian di AS disebabkan oleh aterosklerosis & 500.000 orang meninggal setiap tahun karena infark miokard (Orford, 2005) PJK banyak dijumpai di Inggris, Skotlandia Timur, Finlandia, Scandinavia, Rusia (Orford & Selwyn, 2005) 39% kematian penduduk di UK: infark miokard, stroke (Boyle, 2005)
Similar terms, yet distinct, in both spelling and meaning, can be easily confused:
Arteriosclerosis is a general term describing any hardening (and loss of elasticity) of medium or large arteries (the Greek arteria: artery, sclerosis: hardening); Arteriolosclerosis is any hardening (and loss of elasticity) of arterioles (small arteries); Atherosclerosis is a hardening of an artery specifically due to an atheromatous plaque.
The term atherogenic is used for substances or processes that cause atherosclerosis.
Atherosclerosis: the Greek words athero (gruel or paste or porridge ) referring to the soft lipidrich material in the centre of atheroma, and sclerosis (hardness).
American Heart Association (2002), atherosclerosis is a disease of large and mediumsized arteries characterized by thickening and hardening of the vascular wall
It's the term for the process of fatty substances, cholesterol, cellular waste products, calcium and fibrin (a clotting material in the blood) building up in the inner lining of an artery. The buildup that results is called plaque.
It is commonly referred to as a hardening or furring of the arteries. It is caused by the formation of multiple plaques within the arteries Atherosclerosis is a specific form (type) of arteriosclerosis (thickening & hardening of arterial walls) affecting primarily the intima of large and medium-sized muscular arteries and is characterized by the presence of fibrofatty plaques or atheromas.
Aterosklerosis merupakan penyakit karena membesar atau menebalnya muskuler arteri, dan karakterstik adanya disfungsi endotel, inflamasi vaskuler, akumulasi lipid, kolesterol, kalsium, debris seluler dalam intima dinding pembuluh darah. Akumulasi tersebut menyebabkan terbentuknya plak, remodeling vaskuler, obstruksi luminal akut atau khronik, abnormalitas aliran darah, dan menurunnya suplai oksigen pada organ target (Orford and Selwyn, 2005).
monocyt e chemota ctic protein1 (MCP1) IL-1, TNF, IL-6
VCAM, ICAM, Selectin
Free radicals
PDGF, bFGF
Signs and Symptoms
None: This is referred to as silent ischemia. Blood to your heart may be restricted due to CAD, but you dont feel any effects. Chest pain: If your coronary arteries cant supply enough blood to meet the oxygen demands of your heart, the result may be chest pain called angina. Shortness of breath: Some people may not be aware they have CAD until they develop symptoms of congestive heart failure- extreme fatigue with exertion, shortness of breath and swelling in their feet and ankles. Heart attack: Results when an artery to your heart muscle becomes completely blocked and the party of your heart muscles fed by that artery dies.
None
Chest Pain
Signs & Symptoms
Shortness Of Breath
Heart Attack
Most
commonly affected arteries by atherosclerosis include large and medium sized arteries like aorta, coronary, popliteal and cerebral arteries. Major complications resulting from ischemia due to atherosclerosis include myocardial infarction leading to heart attacks and cerebral infarction leading to strokes. Less common complications include peripheral vascular disease, aneurysmal dilatation due to weakened arterial wall, chronic ischemic heart disease, ischemic encephalopathy and mesenteric occlusion.
Risk Factors in Atherosclerosis
Major risk factors 1) Major Constitutional risk factors: i. Age ii. Sex iii. Genetic factors 2) Major Acquired risk factors: i. Hyperlipidemia ii. Hypertension iii. Diabetes mellitus iv. Smoking v. Hyperhomocysteinemia
Risk Factors
Uncontrollable
Controllable
High blood pressure High blood cholesterol Smoking Physical activity Obesity Diabetes Stress and anger
Sex Hereditary Age
CANINE DIABETES MELLITUS
FELINE DIABETES MELLITUS
HYPERTENSION
OBESITY
Risk Factors in Atherosclerosis
Minor Risk Factors: 1. Environmental influences 2. Obesity 3. Hormones: Estrogen deficiency, oral contracep. 4. Physical inactivity 5. Stressful life 6. Infections (C. pneumoniae, Herpes virus, CMV) 7. Homocystinuria 8. Role of Alcohol Chronic consumption of alcohol may result in increased plasma levels of homocysteine
Risks multiply, with two factors increasing the risk of atherosclerosis fourfold. Hyperlipidemia, hypertension and cigarette smoking together increases the risk seven
Age:
Men > 55 years old Women after menopause Incidence and severity of atherosclerosis is more in men than in women. Prevalence of atherosclerosis is about three times higher in men in 4th decade than in women. Lower incidence in women, especially in premenopausal age is probably due to high levels of estrogens and high-density lipoproteins, both of which have anti-atherogenic influence
Sex
Genetic & Ras
Hereditary
genetic derangements of lipoprotein metabolism predispose the individuals to high blood lipid level and familial hypercholesterolaemia predisposition to atherosclerosis may be related to other risk factors like diabetes, hypertension and hyperlipoproteinaemia.
differences too exist. Blacks have less severe atherosclerosis than Whites.
Familial
Racial
Hyperhomocysteinemia (genetic)
Homocysteine can be recycled into methionine or converted into cysteine with the aid of B-vitamins. Deficiencies of the vitamins folic acid (B9), pyridoxine (B6), or B12 ( cobalamin) can lead to high homocysteine levels Increased levels of homocysteine are linked to high concentrations of endothelial asymmetric dimethylarginine
Homocysteine degrades and inhibits the formation of the three main structural components of the artery, collagen, elastin and the proteoglycans. Homocysteine permanently degrades cysteine disulfide bridges and lysine amino acid residues in proteins, gradually affecting function and structure endothelial injury & inflammation cardiovascular disease
Diabetes millitus
Advanced glycosylation end products/AGEs & Free radical endothelium-dependent relaxation endothelial dysfunction Enhance adhesiveness of platellets
Hyperlipidaemia
The atherosclerotic plaques contain cholesterol and cholesterol esters largely derived from the lipoproteins in the blood. The lesions of atherosclerosis can be induced in experimental animals by feeding them cholesterolrich diet The need of LDL:
Adrenal: synthesis of androgen, estrogen, mineralokortikosteroid & glukokortikoid Hepar: synthesis of bile salt All of cell membrane (Simon, 1998).
Hypertension
Hypertension Endothelial
causes mechanical injury to the arterial wall due to increased blood pressure injury due to persistent high B.P leads to plaque formation as per response to injury hypothesis. systolic pressure of over 160 mmHg or a diastolic pressure of over 95 mmHg leads to 5 times higher risk of developing IHD than in people with normal B.P. (140/90 mmHg or less).
Smoking
The
extent and severity of atherosclerosis are much greater in smokers than in non-smokers. risk is due to reduced level of HDL and accumulation of carbon monoxide in the blood that produces carboxy-haemoglobin and eventually hypoxia in the arterial wall favoring atherosclerosis. also promotes atherosclerosis:
Increased
Smoking
increased platelet adhesiveness raised endothelial permeability sympathetic nervous system stimulation by nicotine. free radical produced by smoking causing endothelial inj ury leading to atherosclerosis
Free radicals macrophages oxidized LDL foam cells uptake by
Minor Risk Factors
1.
Higher incidence of Athr. in developed countries is primarily because of environmental influences. Obesity: Risk is increased if a person is overweight by 20% or more. Use of exogenous hormones like oral contraceptives by women or endogenous estrogen deficiency e.g., in post-menopausal women leads to increased risk. Physical inactivity and lack of exercise increases risk Stressful life style led by aggressiveness, competitive drive, over-ambitiousness and a sense of urgency is associated with enhanced risk of IHD.
2.
3.
4. 5.
The possibility that risk of a atherosclerosis complication increases with oral contraceptive (oral pill containing 0.067 mg menstranol and 0.667 mg ehtynodiol diacetate/kg body weight) on the metabolism of lipids in female rats fed a hypercholesterolemic diet for three months. higher levels of triglycerides and cholesterol in plasma and tissues, increase in aorta observed to be two folds. Activity of lipoprotein lipase of extrahepatic tissue was depressed in experimental group. Activity of plasma LCAT, an enzyme involved in the transport of cholesterol from tissues Animals treated with prolonged oral contraceptives and fed with atherogenic diet, may predispose towards atherosclerosis.
Infections particularly Chlamydia pneumoniae and viruses such as herpesvirus and cytomegalovirus increases coronary atherosclerotic lesions. C. pneumoniae: - Infects the endothelial cells : injury - HSP 60 similar to human endothelial protein - LPS: endothelial injury - Inhibits apoptosis 7. Patients with homocystinuria, an inborn error of metabolism have early atherosclerosis and CAD. 9. Persistent consumption of alcohol in large quantities causes more damage.
6.
Screening and Diagnosis
me a
blo od
sp ec
ifi c
su r
es
me asu r
es
shows
ea rt
Electrocardiogram
lse u mp s
Stress Test
su pp ly
Coronary Angiography
ng in
to h
Narrowi
coronaries
electrical
of es Sit
Other Tests Include...
Blood tests: used to evaluate kidney and thyroid function as well as to check cholesterol levels and the presence of anemia. Chest X-ray: shows the size of your heart and whether there is fluid build up around the heart and lungs. Echocardiogram: shows a graphic outline of the hearts movement Ejection fraction (EF): determines how well your heart pumps with each beat.
TREATMENT
Many people are able to manage coronary artery disease with lifestyle changes and medications. Other people with severe coronary artery disease may need angioplasty or surgery.
Treatment (continued) 1) Stenting
a stent is introduced into a blood vessel on a balloon catheter and advanced into the blocked area of the artery the balloon is then inflated and causes the stent to expand until it fits the inner wall of the vessel, conforming to contours as needed the balloon is then deflated and drawn back The stent stays in place permanently, holding the vessel open and improving the flow of blood.
2) Angioplasty
a balloon catheter is passed through the guiding catheter to the area near the narrowing. A guide wire inside the balloon catheter is then advanced through the artery until the tip is beyond the narrowing. the angioplasty catheter is moved over the guide wire until the balloon is within the narrowed segment. balloon is inflated, compressing the plaque against the artery wall once plaque has been compressed and the artery has been sufficiently opened, the balloon catheter will be deflated and removed.
3) Bypass surgery
healthy blood vessel is removed from leg, arm or chest blood vessel is used to create new blood flow path in your heart
the bypass graft enables blood to reach your heart by flowing around (bypassing) the blocked portion of the diseased artery. The increased blood flow reduces angina and the risk of heart
Get regular medical checkups. Control the blood pressure. Check the cholesterol level. Dont smoke. Exercise regularly. Maintain a healthy weight. Eat a heart-healthy diet. Manage stress.
Prevention
This is a normal coronary artery with no atherosclerosis and a widely patent lumen that can carry as much blood as the myocardium requires.
This is mild coronary atherosclerosis. A few scattered yellow lipid plaques are seen on the intimal surface of the opened coronary artery traversing the epicardial surface of a heart. The degree of atherosclerosis here is not significant enough to cause disease, but could be the harbinger of worse atherosclerosis to come.
The degree of atherosclerosis is much greater in this coronary artery, and the lumen is narrowed by half. A small area of calcification is seen in the plaque at the right.
These cross sections of the left anterior descending coronary artery demonstrate more pronounced atherosclerosis with narrowing at the left, which is the proximal portion of this artery. Atherosclerosis is generally worse at the beginning of an artery where turbulence is greater.
Here is occlusive coronary atherosclerosis. The coronary at the left is narrowed by 60 to 70%. The coronary at the right is even worse with evidence for previous thrombosis with organization of the thrombus and recanalization such that there are three small lumens remaining.
This is the gross appearance of severe coronary atherosclerosis, which involves virtually 100% of the surface of the coronary. There is extensive calcification, especially at the right where the lumen is narrowed.
Manifestasi Klinik
Before the plaques rupture: angina pectoris After the plaques rupture: acute myocardial infarction sudden cardiac death stroke (Worthley et al., 2001; Boyle, 2005), ischaemic (van Haelst et al., 2005).
Adaptive immunity
Terima Kasih
