Atherosclerosis & Aneurysms (L16) PDF

KING ABDULAZIZ UNIVERSITYITY RABIGH BRANCH Faculty of Medicine Cardiovascular System Atherosclerosis (ATH) Dr. Mohamad Nidal Khabaz...

KING ABDULAZIZ UNIVERSITYITY RABIGH BRANCH Faculty of Medicine Cardiovascular System Atherosclerosis (ATH) Dr. Mohamad Nidal Khabaz MD. PhD 2024  KING ABDULAZIZ Pathology of UNIVERSITYITY RABIGH Cardiovascular BRANCH System Learning Objectives Define atherosclerosis, arteriosclerosis, fatty streaks, and fibrous atheromatous plaques, and identify the most common sites of atherosclerosis. List the vessels most affected by atherosclerosis and describe the vessel changes that occur with atherosclerosis and possible complication. Describe possible mechanisms involved in the development of atherosclerosis. Dr. Mohamad Nidal Khabaz  Atherosclerosis (ATH) Hardening of arteries (Thickening and loss of elasticity of arterial walls). Systemic disease at multiple sites affects arteries of vital organs, Elastic arteries, Large arteries, Medium sized arteries. It is common worldwide, almost everyone in U.S is subject to ATH if they live long enough. Accounting for about 50% of all deaths in West. The characteristic lesion of ATH is called atheroma ATH: Atheroma (fibrofatty plaques) Atheroma is focal lesion of intima, that is characterized by intimal deposition of lipids, intruding into the lumen (0.3 to 1.5 cm in diameter), Atheroma leads to intimal thickening, scarring, and reducing the lumen size causing stenosis, which ends with ischemia and infarction. Grossly: Atheroma consist of lipid core covered by a firm white fibrous cap, and have three main components: Cells: including SMCs, macrophages, leukocytes Extracellular matrix, including collagen, elastic fibers, and proteoglycans Intracellular and extracellular lipid. Around the lesions, there is neovascularization. Foam cells are large lipid-laden cells that derive predominantly from blood monocytes (tissue macrophages), but SMCs can also absorb lipid to become foam cells. Two type of atheromatous plaques Soft plaques (abundant lipid). Solid or fibrous plaques (SMCs and fibrous tissue).  Atheroma Plaques change and progressively enlarge through Cell death and degeneration, Synthesis and degradation of extracellular matrix, Organization of thrombus. Atheroma often undergo calcification. Complication: rupture (ulceration or erosion), hemorrhage, thrombosis, aneurysmal dilation Site of atheroma Large BV : Abdominal aorta Iliac In descending order Coronary Popliteal Carotid Circle of Willis. Vessels of the upper extremities are usually spared, The severity of ATH in one artery does not predict its severity in another Complications of Atherosclerosis Major consequences Coronary arteries: IHD (myocardial infarction) Cerebrovascular system: Cerebral infarction (stroke) Aorta: Hypertension and aneurysm formation Peripheral vascular system: Decreased perfusion to extremities causing gangrene of the legs (coagulative necrosis) More consequences (diminished arterial perfusion) Mesenteric occlusion, Sudden cardiac death, Chronic IHD, Ischemic encephalopathy  Fatty streaks Fatty streaks, (composed of foam cells), are not significantly raised and thus do not cause any disturbance in blood flow. They begin as multiple yellow, flat spots (fatty dots) less than 1 mm, then combine into elongated streaks. Fatty streaks appear in the aortas of children regardless of geography, race, sex, or environment. Coronary fatty streaks begin to form in adolescence. The relationship of fatty streaks to atherosclerotic plaques is uncertain.  Gross views of atherosclerosis in the aorta. A. Mild atherosclerosis composed of fibrous plaques, one of which is denoted by the arrow. B. Severe disease with diffuse, complicated lesions.  Morphologic types Fatty dots Atheroma Plaques Complicated Histologic features of atheromatous plaque in the coronary artery. Histologic features of atheromatous plaque in the coronary artery. The plaque shown in A, stained for Elastin (black) demonstrating that - the internal and external elastic membranes are destroyed - The media of the artery is thinned under the most advanced plaque (arrow). Histologic features of atheromatous plaque in the coronary artery. The junction of the fibrous cap and core showing scattered inflammatory cells, calcification (broad arrow), and neovascularization (small arrows)  Atherosclerosis: Risk Factors Non-modifiable risk factors (Constitutional): Age, Sex, Genetics Modifiable risk factors (Major): Hyperlipidemia, Hypertension, Smoking, Diabetes Modifiable risk factors (Other): Diet (obesity), life style (stress), personal habits (lack of regular exercise)  Atherosclerosis Constitutional Risk Factors Age: it is clinically evident after middle age, between ages 40-60 increases the incidence of MI 5 fold. Sex: men > premenopausal women, but men = women by 7th-8th decades (↓ postmenopausal estrogen ?). Genetics: familial predisposition (polygenic) Well-defined hereditary genetic derangement in lipoprotein metabolism (familial hypercholesterolemia) Familial clustering of other risk factors: hypertension or diabetes  Atherosclerosis: Major Risk Factors Hyperlipidemia (Hypercholesterolemia) LDL increases the risk of ATH. HDL has a protective effect (negative risk factor). It mobilizes the cholesterol from tissues to liver, It is increased by exercise High dietary intake Bad fats: cholesterol and saturated fats (egg yolk, animal fats, and butter) Good fats such as omega-3 fatty acids (fish oils), unsaturated fats) Low ratio of saturated to polyunsaturated fats lowers risk. Atherosclerosis - Pathogenesis The Role of Lipids ( Cont…) Causes of hypercholesterolemia. familial hypercholesterolemia diabetes mellitus hypothyroidism nephrotic syndrome alcoholism Lowering levels of serum cholesterol by diet or drug slows the rate of progression of ATH and causes regression of plaques.  Atherosclerosis: Major Risk Factors Hypertension Hypertension: Men ages 45-62 with (BP 169/95) →↑ X 5 of IHD than men with (BP 140/90). Cigarette smoking increases the incidence and severity of ATH in M &F and decreases HDL 1 pack +/day for years→↑ X2-3 of death rate from IHD Diabetes mellitus: is associated with raised circulating cholesterol levels and markedly increases the risk for atherosclerosis. MI (X 2) stroke gangrene (X100- 150)  Atherosclerosis: Other Risk Factors Decrease physical activity (lack of regular exercise) Lifestyle (competitive, stressful with type A personality) Obesity (decrease HDL) Multiple risk factors have multiplicative effect. ATH may develop in absence of known risk factor.  Atherosclerosis: Other Risk Factors (Cont…) Inflammation: Inflammatory cells are present during all stages of atheromatous plaque formation and are intimately linked with plaque progression and rupture. Lipoprotein(a) levels. Lipoprotein(a) is an LDL-like particle that contains apolipoprotein B-100 linked to apolipoprotein(a). Lipoprotein(a) levels are correlated with risk of coronary and cerebrovascular disease, Hyperhomocystenemia: Serum homocysteine levels correlate with coronary atherosclerosis, peripheral vascular disease, stroke, and venous thrombosis. Homocysteine increases platelet adhesion and coagulation abnormalities. Can be caused by low intake of Folic acid, vitamin B  Atherosclerosis – Pathogenesis The Response to Endothelium Injury Hypothesis 1. ATH is considered a chronic inflammatory response of the arterial wall initiated by injury to the endothelium caused by derivatives of cigarette smoke, homocysteine, viruses and other infectious agents, Hyperlipidemia Homodynamic disturbances Tendency for plaques to occur at ostia of exiting vessels, branch points and along the posterior wall of the abdominal aorta (where there are disturbed flow patterns).  Atherosclerosis – Pathogenesis The Response to Endothelium Injury Hypothesis 2. Result in endothelial dysfunction that causes ↑endothelial permeability (Depositions of LDL with its high cholesterol content) expression of EC adhesion molecule (ICAM-1) & (VCAM-1) that mediate adhesion of circulating monocytes, lymphocytes and platelets. (thrombotic potential) followed by their migration into the intima and transformation of macrophages into foam cells.  Atherosclerosis – Pathogenesis The Response to Endothelium Injury Hypothesis 3. Release of factors from activated platelets and macrophages that cause migration of SMCs from media into the intima. 4. Enhanced accumulation of lipids both within cells (macrophages and SMCs) and extracellularly. 5. Proliferation of SMCs in the intima, and elaboration of extracellular matrix, leading to accumulation of collagen and proteoglycans. Sequence of cellular interaction in atherosclerosis The Response to Endothelium Injury  Atherosclerosis - Pathogenesis The Role of Lipids Evidence linking hypercholestrolemia & ATH Increased LDL cholesterol levels, decreased HDL cholesterol levels, and increased levels of the abnormal Lp(a) Lipids in atheromas (plaques) are plasma-derived cholesterol and cholesterol esters. Relationship between increased LDL level and the severity of ATH  Atherosclerosis - Pathogenesis The Role of Lipids (mechanisms) Hyperlipidemia, may directly impair EC function through increased production of oxygen free radicals (in macrophages or EC) that deactivate nitric oxide (the major endothelial-relaxing factor). Free radicals induce chemical changes of lipid in the arterial wall by oxidizing LDL, leading to: Accumulation of lipoproteins (mainly LDL or oxidized LDL) in intima at sites of increased endothelial permeability. Atherosclerosis - Pathogenesis The Role of Lipids (mechanisms) Role of oxidized LDL in atherogenesis Oxidized LDL is ingested through scavenger receptor of macrophages thus forming foam cells. Increases monocytes accumulation in lesion (adhesion) Stimulates release of GF & cytokines Oxidized LDL is cytotoxic to ECs and SMCs Oxidized LDL can induce endothelial cell dysfunction  The Role of Monocytes, Macrophages and Platelets Adhesion of monocytes to ECs, then migration into the intima, followed by transformation into macrophages which engulf lipoproteins largely oxidized LDL to become foam cells. Macrophages produce IL-1 & TNF which increase adhesion of leukocytes Macrophages produce toxic O2 species Macrophages elaborate GF that contribute in SMC proliferation. Adhesion of platelets Release of factors from activated platelets and macrophages that cause migration of SMCs from media into the intima. Atherosclerosis - Pathogenesis The Role of Smooth Muscle Cell Proliferation Proliferation of SMCs in the intima and elaboration of ECM, leading to accumulation of collagen and proteoglycans. Convert fatty streak into a mature fibrofatty atheroma and contribute to the progression of ATH. Enhanced accumulation of lipids both within cells (macrophages and SMCs) and extracellularly. Aneurysms  Aneurysms Abnormal localized dilations of blood vessel or the heart. Develop where there is marked weakening of the wall (congenital, infections, trauma, systemic diseases). True aneurysms: (Atherosclerotic, syphilitic, congenital vascular aneurysms and the left ventricular aneurysm) are of two shapes: Fusiform and Saccular.  Aneurysms False aneurysm: is a tear in the vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space (pulsating hematoma). Aortic dissection (dissecting hematoma), patients with hypertension or with abnormality of connective tissue that affects the aorta (Marfan syndrome). Complications: Thrombosis, Embolism, Rupture  Abdominal Aortic Aneurysm (AAA) Causes Atherosclerosis causes arterial wall thinning through medial destruction. Cystic medial degeneration of the arterial media Focal loss of elastic and muscle fibers in the aortic media and replacement by cystic spaces filled with myxoid material (hypertension, Marfan’s syndrome) Common site is abdominal aorta below the renal arteries and above the bifurcation of the aorta. But the common iliac arteries, the arch, and descending parts of the thoracic aorta can be involved. AAAs are saccular or fusiform, and thrombus frequently fills at least part of the dilated segment.  Abdominal Aortic Aneurysm (AAA) Two variants: Inflammatory AAAs and Mycotic AAAs Males > 50 years old, (50% of patients are hypertensive). Complications: depend primarily on location and size: Rupture into the peritoneal cavity or retroperitoneal tissues with massive hemorrhage. Obstruction of a vessel, particularly of the iliac, mesenteric, renal, or vertebral branches. Embolism from atheroma or mural thrombus. Pressure on an adjacent structure (ureter or vertebrae). Abdominal aortic aneurysm that ruptured. A. Cross-section of aortic media with marked elastin fragmentation and formation of areas devoid of elastin that resemble cystic spaces, from a patient with Marfan syndrome. B. Normal aortic media, showing the regular layered pattern of elastic tissue. In both A and B the tissue section is stained to highlight elastin as black.  Aortic Dissection (Dissecting Hematoma) Entry of blood into the arterial wall, through an intimal tear, usually in the aortic arch, dissecting the media between the middle and outer third, causing massive hemorrhage. Aortic dissection (dissecting hematoma), occurs in patients with hypertension (90%) or with abnormality of connective tissue that affects the aorta (Marfan syndrome). Dissection of the aorta or other branches (coronary) may occur during or after pregnancy (rare). Proximal aortic dissection demonstrating a small, oblique intimal tear (demarcated by the probe), allowing blood to enter the media, creating an intramural hematoma (narrow arrows). Note that the intimal tear has occurred in a region largely free from atherosclerotic plaque, and that propagation of the intramural hematoma is arrested at a site more distally where atherosclerosis begins (broad arrow). Histologic view of the dissection demonstrating an aortic intramural hematoma (asterisk). Aortic elastic layers black and blood red in this section, stained with Movat stain.  Aortic Dissection (Dissecting Hematoma) C/P: Sudden onset of severe pain, beginning in the anterior chest, radiating to the back, and moving downward as the dissection progresses. (Not MI). Aortic dissections are classified into two types: Proximal lesions: more common (dangerous), involving the ascending aorta or both the ascending and the descending aorta (called type A). Distal lesions begin distal to the subclavian artery (called type B) Aortic dissections are classified into two types: A and B.  Aortic Dissection (Dissecting Hematoma) Complication The most common cause of death is rupture of the dissection outward into any of the three body cavities (pericardial, pleural, or peritoneal). Retrograde dissection into the aortic root can cause disruption of the aortic valve causing cardiac tamponade, aortic insufficiency, and myocardial infarction. Extension of the dissection into the great arteries of the neck or into the coronary, renal, mesenteric, or iliac arteries, causing critical vascular obstruction. Thank you