CRS 202 Lecture 1 PDF

CRS 202 Lecture 1 by Dr. Kariman Hussein Lecturer of pathology Theoretical objectives 1-Recognize arterial atherosclerosis and its pathogenesis 2-Describe arteriosclerosis and its types 3-Outline types of aneurysms and dissection of arteries 1)Atherosclerosis (Atheroma)...

CRS 202 Lecture 1 by Dr. Kariman Hussein Lecturer of pathology Theoretical objectives 1-Recognize arterial atherosclerosis and its pathogenesis 2-Describe arteriosclerosis and its types 3-Outline types of aneurysms and dissection of arteries 1)Atherosclerosis (Atheroma) Def.: Patches (plaques) of intimal thickening -accumulation of lipids. -proliferation of smooth muscle cells, inflammatory cells and increased ECM. What are the risk factors for atherosclerosis? Major Minor (additional) Constitutional(fixed): Inflammation, metabolic syndrome, age, male gender, family history of high lipoprotein A , low physical atherosclerosis and genetic defects activity, type A personality, and ( familial hypercholesterolemia) stress. Modified : hypertension, hyperlipidemia, diabetes, and smoking  A t h e r o m a:  Arterial hypertension  Tobacco  Heredity (familial hypercholesterolemia)  Endocrine (diabetes, postmenopausal estrogen deficiency)  Reduced physical activity (sedentary life)  Obesity  Male gender Age Pathogenesis of atherosclerosis according to the reaction to injury hypothesis (i.e., chronic inflammation + healing response) Morphology  1)Fatty streaks: composed of lipid-filled foamy macrophages. Beginning as multiple minute flat yellow spots, they eventually coalesce into elongated streaks 1 cm long or longer.  What are the earliest recognizable lesion of atherosclerosis? 2)Atherosclerotic Plaque:  white-yellow , superimposed thrombus over ulcerated plaques is red- brown.  Plaques vary in size but can coalesce to form larger masses.  On cross-sectioning, it consists of a soft, lipid-rich center covered with a fibrotic capsule. Atheromas are often partially calcified.  Atherosclerotic lesions are patchy, are rarely circumferential; on cross- section, the lesions therefore appear “eccentric” The most extensively involved vessels are: the lower abdominal aorta, the coronary arteries, the popliteal arteries, the internal carotid arteries, and the vessels of the circle of Willis  Microscopic picture  1)Fibrous cap composed of smooth muscle cells and relatively dense collagen.  Beneath and to the side of the cap (the “shoulder”) is a more cellular area containing macrophage, T cells, and smooth muscle cells.  2) Necrotic core, containing lipid (primarily cholesterol and cholesterol esters), debris from dead cells, foam cells (lipid laden macrophages and smooth muscle cells), fibrin, variably organized thrombus, and other plasma proteins.  The cholesterol content is frequently present as crystalline aggregates that are washed out during routine tissue processing and leave behind only empty “clefts.”  The periphery of the lesions demonstrate neovascularization  Moreover, atheroma often undergo calcification. 1)FIBROUS CAP+ (smooth muscle cells, macrophages, foam cells, lymphocytes, collagen) 2)NECROTIC CENTER (cell debris, cholesterol crystals, foam cells, calcium  F C (Masson trichrome stain). (Acute plaque changes):  1) Erosion, ulceration, or Rupture = thrombogenic substances  2) Thrombosis, which may partially or completely occlude the vessel lumen.  3) Hemorrhage into a plaque, intra-plaque hemorrhage; a contained hematoma or induce plaque rupture.  4)Athero-embolism. Atherosclerotic debris into the bloodstream, producing microemboli.  5)Aneurysm formation: causes weakness and potential rupture. Severe disease with diffuse and complicated lesions including an ulcerated plaque (small arrow), and a lesion with overlying thrombus (large arrow) Clinical picture of atherosclerosis  Aorta: Aneurysms , thromboembolism , Cholesterol emboli.  Coronary arteries: ischemic heart disease:, Sudden occlusion by thrombi causes infarct.  Carotid arteries: cerebral ischemia, cerebral and ocular infarcts.  Cerebral arteries : Transient ischemic attack and stroke, Multi-infarct dementia.  Major intestinal arteries: ischemic bowel disease.  Renal artery stenosis: Renal ischemia is associated with reduced renal function and hypersecretion of renin and hypertension.  Iliac, femoral, and popliteal arteries: Intermittent claudication or ischemic gangrene is seen. 2)Arteriolosclerosis (;HTN)  Arteriolosclerosis affects smaller arteries and arterioles and may cause downstream ischemic injury.  A)hyaline  B)hyperplastic Morphology  A) Hyaline arteriolosclerosis: homogeneous, pink hyaline thickening with associated luminal narrowing.  -plasma protein leakage across injured endothelial cells  -increased smooth muscle cell matrix synthesis (in response to the chronic hemodynamic stresses of benign hypertension) b) Hyperplastic Arteriolosclerosis: vessels exhibit concentric, laminated (“onion-skin”) thickening of the walls with luminal narrowing, (smooth muscle cells with thickened, reduplicated basement membrane) In malignant hypertension, they are accompanied by fibrinoid deposits and vessel wall necrosis (necrotizing arteriolitis), particularly in kidney.  What are complications of hypertension?  The most affected organs are the heart, aorta, brain, eyes, and kidneys: -Hypertrophy of the left ventricle -Aortic dissection and aneurysms -Hypertensive stroke -Hypertensive encephalopathy with headache and cerebral dysfunction -Hypertensive retinopathy -Hypertensive renal disease Any Question???  4)Aneurysms  Def. An aneurysm is a localized abnormal dilation of a blood vessel or the heart. Types: 3 classifications 1 -Congenital: cerebral ‘‘berry’’ aneurysms on the circle of Willis or Acquired 2-Saccular aneurysms: involving only a portion of the vessel wall. from 5 to 20 cm in diameter and often contain thrombus. Or Fusiform aneurysms: circumferential dilations of a long vascular segment; (up to 20 cm) and in length and can involve extensive portions of the aortic arch, abdominal aorta, or even the iliacs. 3-True aneurysm: its wall is formed by 1 or more layers of affected vessels. False aneurysm: its wall is formed by connective tissue which is not part of vessel Pathogenesis of Aneurysms  1)The intrinsic quality of the vascular wall connective tissue is poor ( Marfan syndrome)  2)The imbalance of collagen degradation and synthesis: increase MMProtinase by inflammation and atherosclerosis.  3)The vascular wall is weakened by ischemia caused by HTN and Tertiary syphilis (involve the ascending aorta and its arch) lead to ischemic injury of the aortic media and aneurysmal dilation.  The two most important causes of aortic aneurysms are atherosclerosis and hypertension  Morphology of abdominal aortic aneurysm (AAA)  1)Atherosclerotic:  below the renal arteries or above the iliac bifurcation of the aorta, saccular or fusiform.  Destruction and thinning of the aortic media; with mural thrombus.  2)Inflammatory:  occur in younger patients, who often present with back pain and elevated inflammatory markers (e.g., C-reactive protein).  Abundant lymphoplasmacytic inflammation with macrophages (localized immune response).  3)Mycotic:  become infected by the lodging of circulating microorganisms in the wall. the lumen is filled by a large quantity of layered but largely unorganized thrombus.  Symptoms of AAA:  Asymptomatic or abdominal mass (often palpable pulsating).  Rupture with massive, potentially fatal hemorrhage  Embolism from atheroma or mural thrombus  Obstruction of a vessel branching off from the aorta, resulting in ischemic injury to the supplied tissue e.g., renal (kidney), mesenteric (gastrointestinal tract)  Compression on an adjacent structure e.g., ureter or erosion of vertebrae  Symptoms of Thoracic aortic aneurysms : Associated with hypertension, other causes such as Marfan syndrome (1) Rupture. (2) respiratory difficulties, difficulty in swallowing. (3) persistent cough due to compression of the recurrent laryngeal nerves. (4) Pain caused by erosion of bone (i.e., ribs and vertebral bodies). (5) cardiac disease as the aortic aneurysm leads to aortic valve dilation.  What is aortic dissection?  Aortic dissection, previously called dissecting aortic aneurysm  Def.: forceful separation of the layers of the aortic wall due to the entry of blood between the layers.  It results from a tear in the intima  Intramural hge dissecting between layers of vessel wall What are the common causes of aortic dissection?  In older people who have hypertension Other causes: Cystic medial necrosis. (This disease is characterized by fragmentation of elastic fibers). Marfan disease, Ehlers–Danlos syndrome or osteogenesis imperfecta. What is the outcome of aortic dissection?  High mortality. Fatal heamorrhage into the retroperitoneal spaces or the abdominal and thoracic cavity.  Dissection of the initial intra pericardial portion of the aorta may cause cardiac tamponade. References -Pocket companion to Robbins & Cotran Pathologic Basis of Disease, 9th edition. Richard N. Mitchell, Vinay Kumar, Abul K. Abbas & Jon C. Aster. Elsevier, 2017. -Robbins & Cotran Pathologic Basis of Disease, 10th edition. Vinay Kumar, Abul K. Abbas & Jon C. Aster. Elsevier, 2018. -Pathology secrets, Ivan Damjanov. MOBSY Elsevier, 3rd edition. -https://library.med.utah.edu/WebPath/EXAM/EXAMIDX.html Thank you