Pathology of Blood Vessels PDF

Pathology of Blood Vessels Dr Derek TW Yau Email: [email protected]  Overview of artery system Nutrient, O2 Immune cells, etc Elastic fibers: ↓energ...

Pathology of Blood Vessels Dr Derek TW Yau Email: [email protected]  Overview of artery system Nutrient, O2 Immune cells, etc Elastic fibers: ↓energy loss during flow Muscular: control vascular resistance R is inversely proportional to d4 Arteriole: fine tune flow to capillaries Waste, CO2 Acid, etc  Thrombosis Pathologic – Vs physiologic hemostasis – Due to disturbed balance between antithrombotic and prothrombotic processes – Thrombosis involves Activation of platelets Activation of coagulation pathways Endothelial cells Vascular stasis  Virchow triad Turbulence (bifurcation, aneurysm) Endothelial Hypertension injury Cytokine/Infection AGE products Cigarette/ toxin/ foreign body Immobilization Clotting factors Hyper- Stasis abnormalities (FV Leiden, lack coagulability protein C) Dilated lumen (e.g. aneurysm, heart chamber Oral dilation) Contraceptive Trauma Atrial fibrillation Cancer  Clotting: Fibrin formation Cascade of processes – End product of fibrin polymer by thrombin Intrinsic vs extrinsic pathway – Contact activation vs tissue factor activation Collagen exposure  Role of platelets Injury – platelet adhesion (facilitated by vWF): degranulation and platelet thrombus + initiate clotting cascade (complex thrombus) Promoters of platelet aggregation – thrombin, collagen, ADP, thromboxane A2, platelet-activating factor (PAF), epinephrine, and vasopressin  Important Role of Endothelium Procoagulant Anti-coagulant TFI Platelet Protein C Inhibit Thrombom Lyse clot odulin Clotting cascade Plasmin PGI2/NO Injury Tissue factor ADP Plasminogen vWF metabolize Collagen  Fate of a clot Propagation – Increase in size Lysis – Dissolves (thrombolytic activity of the blood) Organization – Recanalization Embolization – Becomes dislodged and travels to other sites  Diseases of blood vessels Arteriosclerosis/ Arteriolosclerosis – “Hardening” of the arteries/ arterioles – Former caused by atherosclerosis Mönckeberg medial sclerosis – Calcifications of the medial layers (no clinical effect) Fibromuscular intimal hyperplasia – In muscular arteries, represent healing response Vasculitis  Blood vessel functions fail Fail to contain blood – Hemorrhage Fail to maintain vascular tone/ blood flow – HT/ hypotension (can lead to shock) – Ischemia/ infarct  Types of infarcts Pale infarct – Heart, kidney, spleen Red infarcts – in organs with a dual blood supply (e.g. lung), or with extensive collaterals (e.g., small intestine, brain) Cystic infarct – E.g. brain Septic infarct – Superimposed bacterial infection  Atherosclerosis – Classic atherosclerotic lesion fibroinflammatory lipid plaque at luminal surface (atheroma) – Develop over decades multiple gene polymorphisms interact with one another and environment – Genetic (hereditary) familial hypercholesterolemia  Risk Factors for Atherosclerosis Elderly/ Male Physical inactivity/stress/smoking Hypertension/Diabetes Blood cholesterol level – Bad cholesterol: atherogenic (LDL, VLDL) Vs Good cholesterol: antiatherogenic lipoproteins (HDL) – HDL carry cholesterol (including from vessel) to liver for elimination  Risk Factors for Atherosclerosis Familial hypercholesterolemia (LDLR) Apolipoprotein E Lipoprotein a Homocystinuria Infection  Precursor Lesions of Atherosclerosis – Fatty streak (yellow) Subendothelial lipid accumulation Starts in childhood – Intimal cell mass (white) At branch points in the arterial tree Smooth muscle cells + connective tissue; no lipid  Established Lesions of Atherosclerosis Fibroinflammatory lipid plaque – Elevated/flat, pale yellow, smooth-surfaced lesions Over many years Precursor Established Fatty Streaks atherosclerosis Intimal cell mass (plaques)  Structure of an atheroma Endothelium - fibrous cap – necrotic core – Fibrous cap: smooth muscle cells, matrix, lymphocytes, foamy histiocytes – Cholesterol crystals/ foreign-body giant cells – Neovascularization contribute to plaque growth and complications  Composition of atheroma Mesenchymal /SMC  Pathogenesis of Atherosclerosis Flow turbulence – shear stress: endothelial dysfunction, lipid accumulation Oxidized LDL – Recruits/activates macrophages – Lipid accumulation, release growth factors (↑ smooth muscle cells) Highly dynamic/ complex process Not always “stable”!!  Plaque with complication A complicated plaque – Erosion/ulceration/fissure/intralesional hemorrhage  potentiate stenosis – Mural thrombosis +/- embolization/ aneurysm formation – In coronary system: Clinical manifest as “Acute coronary syndrome”  Complicated plaque Hemorrhage Clotting Cascade -Thrombosis -Emboli  Complications of Atherosclerosis Effects: – Luminal stenosis  compromise flow ischemia Heart – Ischemic heart disease/ myocardial infarction Brain – Stroke Others – gangrene of the extremities (peripheral vascular disease) or viscera Chronic effect: atrophy of end tissue – Thromboembolism/ Aneurysm  Arterial Aneurysms Localized (congenital or acquired) dilations of blood vessels due to weakness of the media Cause: atherosclerosis, traumatic, mycotic, syphilis Fusiform Different forms – Fusiform – Saccular (e.g. berry aneurysm of cerebral arteries) Saccular  Arterial Aneurysms – (Pseudo aneurysms – injured vessel with hematoma) Complications – Rupture, dissection, thrombosis +/- emboli  Aortic Dissection Intimal tear – Blood tracks, create a false lumen (inner 2/3 and outer 1/3 media) – re-enter the lumen or perforate with massive bleed – Obstruction HT, Marfan/ Loeys- Dietz/ Turner’s, inflammation  Hypertension (Systemic arterial hypertension) Blood pressure = cardiac output x systemic vascular resistance – Influenced by renal function, sodium homeostasis, renin-angiotensin system (sympathetic output/ vasoconstriction, mineralocorticoid) Primary hypertension (95%) Secondary hypertension  Acquired Causes of Hypertension (Secondary HT) Renal artery stenosis, coarctation of the aorta Renal disease, hyperendocrine (aldosterone, Cushing syndrome, pheochromocytoma, hyperthyroidism) Tumor (with renin secretion)  Pathology of hypertension Hyaline arteriolosclerosis – Arterioles with homogeneous, pink hyaline thickening and luminal narrowing Hyperplastic arteriolosclerosis – In malignant hypertension: concentric, laminated (“onion-skin”); fibrinoid necrosis (usu. in kidney) Emergency: markedly ↑BP, rapid organ damage Atherosclerosis Malignant Hypertension  Pathology of hypertension In the end… –Damaging effect on blood vessels ultimately cause ischemia and organ damage E.g. Benign nephrosclerosis: arteriolar narrowing causes glomerular scarring; Cardiovascular disease; Cerebrovascular disease – Aortic dissection/ rupture aneurysm  Pulmonary hypertension Pulmonary arterial system – Normally a low pressure system Pulmonary HT caused by – left heart failure, congenital heart disease, valve disorders, obstructive or interstitial lung disease, recurrent thromboemboli to lung Pathology – Fibrointimal hyperplasia of pulmonary arteries  Disorders of venous system Varicose Veins Esophageal varices Superficial thrombophebitis Deep venous thrombosis  Deep venous thrombosis Thrombosis affects leg/ pelvic veins – Fate same as before (Lysis, Organization, propagation and embolization) Pulmonary embolization Effect of pulmonary embolism depends on – Size and distribution of emboli; Acute or chronic  Deep venous thrombosis Smaller pulmonary emboli – Pulmonary Infarction settle in peripheral pulmonary arteries Pathology: hemorrhagic and pyramidal with base on pleural surface – Chronic small emboli Chronic pulmonary hypertension  Deep venous thrombosis Large pulmonary emboli – block main pulmonary arteries or their first branches (e.g. saddle embolus at the bifurcation of the main pulmonary artery) – Hemodynamically important: shock – Embolization to smaller pulmonary branches can occur  Deep venous thrombosis Paradoxical Embolism – emboli from venous circulation to organs other than the lungs; – direct access of systemic circulation through right-to-left shunt (e.g. patent foramen ovale)  Other forms of embolism Air Embolism – Air enter the venous circulation – 100 ml can result in sudden death – Decompression sickness in scuba divers: nitrogen bubbling from blood with rapid ascent Amniotic Fluid Embolism – Complication of childbirth – Amniotic fluid enter maternal circulation through open uterine and cervical veins  fatal consumptive coagulopathy  Other forms of embolism Fat and marrow embolism – following severe trauma, particularly accompanying bone fractures  Vaculitis Vasculitis: – Inflammation + damage of blood vessels – May affect arteries, veins, and capillaries, or combination thereof – Etiology: autoimmune, infectious agents, mechanical trauma, radiation, toxins, idiopathic – Classified by size and distribution of vessels involved, etiology and clinical Vasculitis (Churg –Strauss)  Takayasu Arteritis Young woman 60 yr old Aortic aneurysms and dissection occur  Giant cell (temporal) arteritis Gross Pathology: cord-like, nodular thickening of temporal artery Microscopic: Mixed inflammation (+ granuloma and giant cells), giant cells tend to be at internal elastic lamina, vessel damage with necrosis/ fragmented internal elastic lamina, stenotic lumen  Polyarteritis Nodosa – medium-sized/ smaller muscular arteries – occasionally larger arteries – Causes: viral infections such as HBV/HCV and HIV – Pathology: segmental (predilection at branch point), mixed transmural inflammatory infiltrate, fibrinoid necrosis  Polyarteritis Nodosa Healing phase (after tx) fibrosis and gaps of the media Complication: thrombosis, infarct, aneurysm Gap in vessel  Microscopic Polyangiitis Reaction to foreign materials (e.g., bacterial products or drugs) If mostly skin – leukocytoclastic vasculitis (nuclear debris from disintegrating neutrophils) Affects smallest arterioles Strongly associated with p-ANCA.  Wegener granulomatosis Aka Granulomatosis with polyangiitis (GPA) Over 90% of patients positive for ANCA (mostly c-ANCA) Pathology (triad): – Acute necrotizing granulomas of the respiratory tract (upper and/or lung)  Wegener granulomatosis Pathology (triad): – Necrotizing or granulomatous vasculitis affecting small- to medium-sized vessels (often lungs and upper airways) – Focal necrotizing, often crescentic, glomerulonephritis  Irregular geographic “dirty” with neutrophils Vasculitis: fibrinoid necrosis of media  Churg–Strauss Syndrome Allergic Angiitis and Granulomas – Preceded by severe asthma/ tissue eosinophilia – >60% p-ANCA (antineutrophil cytoplasmic Ab) – Necrotizing eosinophilic vasculitis (small to medium sized vessels) involving all major organ systems – Microscopy: granulomas + abundant eosinophilic infiltrates + fibrinoid necrosis in blood vessel/ adjacent soft tissue Churg–Strauss Syndrome  Kawasaki Disease Aka mucocutaneous lymph node syndrome – an acute necrotizing vasculitis of infancy and early childhood – high fever, skin rash, conjunctival and oral lesions, and lymphadenitis – 70% vasculitis of the coronary arteries  coronary artery aneurysms  Buerger Disease Aka thromboangiitis obliterans – occlusive inflammatory disease of medium- /small-sized arteries in the distal arms and legs, “corkscrew” arteries ankle/wrist – mostly in young to middle-aged men who smoked heavily – Microscopic: Neutrophilic vasculitis, extension to adjacent veins and nerves Microabscesses of the vessel wall Thrombosis and lumen obliteration  Behçet Disease A systemic vasculitis characterized by oral aphthous ulcers, genital ulcers, and ocular inflammation Occasionally, there are lesions in the CNS, gastrointestinal tract, and cardiovascular system Large and small vessels show vasculitis  Infectious vasculitis Caused by bacteria or fungi (Aspergillus and Mucor, so-called invasive fungal infection) Secondary involvement next to localized tissue infection (e.g., bacterial pneumonia or adjacent to abscesses) or hematogenous spread from focus of infection e.g. bacterial endocarditis  Vascular tumours Classification: benign, borderline and malignant – Hemangioma, hemangioendothelioma, angiosarcoma “Intravascular tumors” – Not vascular tumours per se: Other lineage of tumours but prominent intravascular growth e.g. IV leiomyomatosis, nodular fasciitis; intravenous growth of malignancy e.g. HCC  Summary Clotting – Pathologic mechanism – Fate Blood vessel – Atherosclerosis Mechanism, Plaque complication – Arterial system and venous system disease – Inflammation of vessels Clinicopathologic features of various forms – Tumours Dr Derek, Tsz Wai Yau [email protected]