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to tissue (lead to cell death) Normal Haemostasis Vascular injury Brief period of vasospasm Exposure of subendothelial collagen Platelet adhesion, activation Platelet aggregation (1° haemostasis) Release of TF (tissue factor) Activation of coagulation sequences Formation of fibrin Permanent haemostatic plug (2° haemostasis) Coagulation Cascade
3 Important Factors Vascular wall lining y Endothelium y Sub-endothelium connective tissue Platelets haemostatic plug Coagulation system activated in cascade fibrin formation Effects Anti-Thrombotic Pro-Thrombotic Anti-platelet effects Platelet adhesion, aggregation Anti-coagulation properties y VW factor y Heparin like molecules y Platelet activating factors Procoagulant factors y Thrombodulin activation of protein C, S y Tissue factor y 2 macroglobulin y Binding sites for factor IX, X, V Fibrinolysis Inhibition of fibrinolysis (tissue plasminogen activator) (t-PA inhibitor)
Thrombosis Definition Pathological process, denotes formation of clotted mass of blood Within non-interrupted vascular system Inappropriate activation of normal haemostatic process Thrombogenesis (Virchow s Triad) Endothelial injury Especially thrombi of heart, arteries Causes y Myocardial infarction y Myocarditis y Atherosclerosis y Inflammatory valve diseases y Prosthetic heart valves Haemodynamic stress in y Hypertension y Radiation y Chemicals y Bacterial toxins y Hypercholesterolaemia y Immune reaction Alteration in Blood Flow Turbulence y Arterial, cardiac thrombi y Eg. Over ulcerated AS plaques, aneurysms, MI, healed rheumatic MS Stasis y Venous thrombi y Eg. Varicose veins, hyperviscosity syndrome (polycythemia) Alteration in Blood (Hypercoagulability) Primary Secondary Antithrombin III deficiency Prolonged bed rest, immobilization Protein C, S deficiency Myocardial infarction Fibrinolysis defects Tissue damage Cardiac failure Disseminated carcinoma DIC Prosthetic heart valves Morphology Heart/ aorta y Lines of Zahn y Alternating pale layers of platelet, fibrin separated by darker layers of red cells Veins y No line of Zahn y Resemble coagulated blood Mural thrombi Vegetations Thrombi Arterial Coronary, cerebral, femoral Superimposed on AS lesions Pale, gray white, friable Line of Zahn + Firmly attached to vascular wall Contraction of lumen restoration of blood flow Can propagate both ways Vegetations Bacterial/ Infective Endocarditis Blood borne infection of heart valves Thrombi laden with microorganisms Non-Bacterial Thrombotic Endocarditis Uninfected valves Old patient with terminal Ca Chronic illness Due to y Hypercoagubility y Subendocardial injury Venous DVT veins of lower limbs Stasis (major cause) Red blue, ill-defined pale gray fibrin strands Attached to underlying wall Propagation in both directions Difference Thrombus, Clot Thrombus Living animals Flowing stream Platelet initiation Dry, friable, granular Shape not confined to vessel Line of Zahn + Withdrawal difficult
Clot Dead animals Static blood stream No platelet scaffolding Moist, shiny, gelatinous Shape confined to vessel Red, current jelly app Withdrawal easy
Fate of Thrombus Propagation obstruction of major vessels, ischemia Embolization Dissolution removed by fibrinolysis Organization, fibrosis incorporated into wall Recanalization, establishment of blood flow Central softening, septic mass
Embolism Definition Detached intravascular liquid, solid, gaseous mass Carried by blood to a site (distant from its point of origin) Types Pulmonary embolism Systemic embolism Amniotic fluid embolism Gaseous embolism Fat embolism Tumour embolism Therapeutic embolism Misc. Pulmonary Embolism DVT of legs (90%) Carried along progressively larger channels Right heart Pulmonary vasculature DVT common in Prolonged immobilization Postoperative state Obesity Prolonged use of OCP Heart disease Neoplasia Systemic disease (collagen anomalies) Primary hypercoagulable state Effects Fatal massive PE (results in saddle embolus at pulmonary bifurcation) Right heart failure (Cor pulmonale) Multiple emboli pulmonary hypertension, right heart failure Small multiple PE in medium sized arteries (pulmonary haemorrhage) Emboli in small end-arterioles (infarction) Form delicate bridging fibrous webs Embolus pass through interarterial/ interventricular septal defect y Systemic circulation, obstruct middle sized arteries y Paradoxical embolism Pulmonary Thromboembolus Large vein in leg IVC Main pulmonary arteries Thrombi embolize most often from large veins in legs, pelvis (thrombi form with stasis) Fat Embolism Fracture of long bone Multiple fracture of ribs in extensive cardiac massage Sickle cell anaemia infarct BM Rupture fatty liver Interosseous phlebography Tumour Embolism Tumour invasion of local blood vessel Chronic DIC vessel obstruction, haemorrhage Therapeutic Embolism Gel foam Muscle Silicon Miscellaneous Embolism FB bullets, talc, silk, polythene tube, fiber Parasites schistosoma PV liver Red cell aggregates Microemboli athroma, platelets, fibrin, Ca, silicon, fat Amniotic Fluid Embolism Sudden respiratory difficulty Cyanosis CV shock Tonic-clonic convulsion Coma If survive Pulmonary edema ARDS Excessive uterine bleeding Due to DIC (disseminated intravascular coagulation) Causes Tear in placental membrane/ rupture of uterus, cervical vessels (infusion of amniotic fluid into maternal circulation) Epithelium squame, lanugo hair, vernix caseosa, mucin, bile, meconium in pulmonary microcirculation at PM Air, Gaseous Embolism Air Embolism Gaseous Embolism (Decompression sickness) Exposed to sudden change in ATM
Causes Cervical operation Pressure released Blood transfusion, IV infusion Rupture of venous sinuses in labor Bubble of gas come out Tubal insufflations Form gas masses in vessels/ tissue Stab wound chest Treatment of pneumothorax Haemodialysis Consequences ARD Convulsion Coma Pathophysiology Respiration under pressure Gas dissolved in blood, tissue fluid Rapid decompression Release of O2, N2 O2 dissolves, N2 forms bubbles Occlusion of vessels
Saddle Pulmonary Thrombo Embolus (TE) Infective Emboli Result from infective thrombi (eg. Valvular vegetation in bacterial endocarditis) Infective agent weaken vessel wall mycotic aneurysm
Vegetation on Heart Valves Systemic Embolism Embolism through arterial circulation Thrombi of heart (especially left ventricle MI, RHD) (80-85%) Detached arthroma in large arteries Effects infarct, gangrene Septic emboli suppurative foci
Infarction Definition Area of ischemic necrosis In a particular tissue Caused by occlusion of arterial supply/ venous drainage Thrombic/ embolic events (Almost from arterial occlusion) (99% of infarct) Types (Colour) White/ Anaemic Solid tissue Due to arterial occlusion
Red/ Haemorrhagic Due to venous occlusion y Loose tissue y Tissue with double circulation y Previous congested tissue
Types (Presence/ absence of bacterial infection of infarct area) Septic infarct Bland infarct Morphology Gross Wedge shaped Apex points towards occlusion point Base at periphery Pale yellow white Sharply demarcated Bordered by narrow rim hyperaemia Surface covered w. fibrinous exudates Histology Coagulative necrosis (except brain liquifactive necrosis)
Acute renal infarct Wedge shape (pale) infarct zone of coagulative necrosis
Recent Myocardial Infarction Tan center Surrounding hyperaemia Infarction is transmural Extends through full thickness of wall
Factors influencing development of Infacts Nature of vascular supply Dual arterial supply Parallel arterial supply End arteries with rich anastomosis End arteries with poor anastomosis Rate of development of occlusion Slow occlusion - risk of infarct Extent of obstruction Complete obstruction - risk Vulnerability of tissues to hypoxia Neurones Myocardium Proximal tubular cells of kidney Oxygen content of blood Clinical Correlations of Thromboembolic diseases Arterial thrombi in small vessels Occlusive infarct, gangrene Venous thrombosis DVT of legs fatal pulmonary embolism Occlusive venous thrombi in leg Swelling Edema Tender Fluid/ gas embolism Pulmonary circulation/ tissues
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