Thrombosis and Shock Protein - poor edema (increased
hydrostatic pressure or reduced plasma Edema - An abnormal increase in interstitial protein) fluid within tissues. Individuals suffering from heart failure, 60% of lean body weight is water renal failure, hepatic failure, o 2/3 of the bodys water = malnutrition intracellular compartment o 1/3 of the bodys water = Exudate extracellular compartment Protein rich edema (increased o 5% of total body water = blood vascular permeability) plasma Losses of >20% of blood volume lead to Transudate: def. protein-poor, s.g.< 1.012, hemorrhagic shock secondary to hydrodynamic impairments Edema def. fluid in interstitial tissue. Exudate: def. protein-rich, s.g.>1.012, secondary to inflammation and increased Pathophysiology: vascular permeability Increased Impaired venous Hydrostatic return (CHF, Hyperemia and Congestion Pressure cirrhosis, Hyperemia def. active process of thrombosis) arteriolar dilation leading to local Arteriolar dilation increase in blood volume. (heat) Congestion def. passive process of increase in blood volume due to Reduced Nephrotic impaired outflow. Plasma syndrome, Chronic pulmonary congestion: septa Oncotic Malnutrition, thickened and fibrotic, hemosiderin- Pressure Cirrhosis laden macrophages (heart failure cells) Lymphatic Inflammatory, Acute hepatic congestion: central veins Obstruction Neoplastic, Post- and sinusoids are distended and there surgical may be central necrosis. Sodium Renal insufficiency, Chronic passive congestion: nutmeg Retention Hyperaldosterone liver, centrilobular necrosis and hepatic Inflammation Acute, Chronic, fibrosis (cardiac cirrhosis). Angiogenesis Hemorrhage def. extravasation of blood because of Fluid collections in different body cavities: vessel rupture. Accumulation is Hydrothorax a hematoma. Hydropericardium 1-2 mm petichiae: thrombocytopenia, Hydroperitoneum (Ascites) uremia, clotting factor deficiencies > 3 mm purpura: trauma, vasculitis, Anasarca - Severe and generalized edema with amyloidosis. wide spread subcutaneous tissue swelling. > 1-2 cm ecchymoses: trauma, clotting factor deficiencies, worsened by all of the above o hemoglobin (red-blue) o bilirubin (blue-green) local, weak anticoagulants o hemosiderin (gold-brown) urokinase-like tPA, tissue-type tPA PGI2: vasodilator, inhibits platelet Hemostasis and Thrombosis aggregation Normal Hemostasis: TXA2: vasoconstrictor, activates platelet 1. Vasoconstriction - endothelin aggregation (aspirin blocks synthesis, by 2. Platelet adherence and activation - primary acetylating cyclooxygenase) hemostatic plug 3. Coagulation cascade stimulated by the Thrombosis release of tissue factor - leads to activation of Virchow's triad: endothelial injury, thrombin - secondary hemostatic plug stasis, hypercoagulability 4. Permanent plug counter regulatory Hypercoagulable states: Factor V mechanisms [t-PA] Leiden, Protein C/S deficiency, homocysteine, prothrombin mutations - Endothelium: has pro-coagulant and anti- Hyperestrogenic states (pregnancy, thrombotic properties. OCP): increased hepatic synthesis of - Intact endothelium is anti-platelet (PGI2, NO, certain coagulation factors and reduced ADP), anti-coagulant (heparin-like molecules, synthesis of antithrombin III. thrombomuodulin, antithrombin III), fibrinolytic Disseminated cancers: procoagulant (t-PA) tumor products - Endothelial injury leads to adhesion of Age: increasing platelet aggregation and platelets via vWF, synthesizes tissue factor (TNF, reduced PGI2. IL-1), PAIs (plasminogen activator inhibitors) Factor V Leiden Platelets Alpha granules: P-selectin, fibrinogen, Clinical: 2-15% white population fibronectin, factor V, vWF, plateket Pathophysiology: Mutant factor V factor 4, PDGF, TGF-b Leiden cannot be inactivated by Dense bodies (d granules): ADP, ATP, protein C Ca, histamine, serotonin, epinephrine Cytogenetics: arginine glutamine Adhesion: vWF - glycoprotein Ib, at position 506 fibrinogen Secretion: granules, ADP mediates Heparin-Induced Thrombocytopenia aggregation Aggregation: ADP, TXA2, thrombin, Clinical: 5% of population platelet contraction, GpIIb-IIIa receptors Pathophysiology: Rx with unfractionated heparin results in formation of antibodies to Clotting Cascade heparin platelet factor 4. Once activated must be restricted to Treatment: low molecular weight the site of vascular injury to prevent heparin preparations, retain clotting of the entire vascular tree. anticoagulant activities but do not Antithrombin III: inactivates IX, X, XI, XII interact with platelets and II Protein C & S: inactivate V and VIII Antiphospholipid Antibody Syndrome Plasmin: breaks down fibrin into FSP (fibrin split products), which can act as Clinical: Multiple thromboses associated with high serum titers to membrane phospholipids Venous thrombi: asymptomatic in 50%. Risk (cardiolipin). Autoimmune factors include CHF, trauma, surgery, burns, associated type exists. puerperal and postpartum states, disseminated Recurrent venous or arterial cancers (see TRousseau's syndrome - migratory thrombi, repeated miscarriages, thrombophlebitis). cardiac valce vegetations, Cardiac thrombi: brain, kidneys and spleen are thrombocytopenia, 7% increased prime targets. risk of sudden death. DIC is a potential complication of any condition Two clinical groups: one associated with widespread activation of associated with SLE, the other thrombin. shows only hypercoagulability Embolism def. detached intravascular solid, without lupus. liquid, or gaseous mass that is carried by the Arterial thrombi occur in sites of blood to a site distant from its point of origin. injury while venous occur due to 99% are dislodged thrombi. stasis. Transmission: Pulmonary Thromboembolism Pathophysiology: Abs interfere with Clinical: 20-25/100,000 coagulation in vitro but induce hospitalized patients; 95% from hypercoagulative state in vivo (via direct deep leg vein thrombi above the platelet activation, PGI2 or protein C knee. inhibition) Rarely may pass through an interatrial or interventricular Micro: Lines of Zahn imply thrombosis at defect to gain access to the sites of blood flow. Arterial thrombi systemic circulation (paradoxical (retrograde propagation) at coronary, embolism). cerebral and femoral arteries. Venous 60-80% clinically silent (small). thrombi propagate in the direction of blood flow; 90% lower extremities. When 60% or more of the pulmonary circulation is Diagnosis: False positive VDRL (embedded obstructed leads to sudden death, in cardiolipin). Also present in 5-15% of right heart failure or normal individuals. cardiovascular collapse. Treatment: Anticoagulation with aspirin, Micro: Usually causes pulmonary heparin, coumadin, prednisone for hemorrhage not infarction(dual recurrent miscarriages and blood supply) unless in the setting immunosuppression in refractory cases. of left sided cardiac failure.
Fate of a Thrombus: Systemic Thromboembolism
1. Propagation Clinical: 80% arise from 2. Embolization intracardiac mural thrombi (2/3 3. Dissolution assoc with LVW infarcts, 1/4 with 4. Organization & Recanalization. dilated L atria); remainder arise With older thrombi extensive fibrin from aortic aneurysms, plaques or polymerization renders the thrombus valve vegetations. 75% go to more resistant to proteolysis. lower extremities and 10% go to May become a culture medium for the brain. bacteria - mycotic aneurysm. Fat Embolism hypotensive shock, followed by Clinical: After fractures of long seizures and coma. Pulmonary bones, soft tissue trauma or edema and DIC. burns. 90% of individuals with Micro: Pulmonary severe skeletal injuries, though microcirculation with epithelial <10% have any clinical findings. squamous cells shed from fetal Fat embolism syndrome begins 1- skin, lanugo hair, fat from vernix, 3 days after injury with mucin from GI tract. Pulmonary tachypnea, dyspnea and edema and DAD. Systemic fibrin tachycardia, neurologic sx, diffuse thrombi (DIC). petechial rash (20-50%), thrombocytopenia, anemia. Infarction Pathophysiology: Mechanical def. area of ischemic necrosis caused by obstruction and biochemical occlusion of either arterial supply or injury. Free fatty acids cause local venous drainage. 99% from thrombotic toxic injury to endothelium, or embolic events. Remainder: local platelet activation. vasospasm, extrinsic compression, Prognosis: Syndrome fatal in 10%. hemorrhage within a plaque, torsion, traumatic rupture. Infarcts caused by venous thrombosis are more common Air Embolism in organs with single venous outflows: AKA: Decompression sickness, e.g. testis, ovary. "the bends" or "the chokes", Red Infarct (hemorrhagic): venous caisson disease occlusions, loose tissues (lung), dual Clinical: In excess of 100cc circulations, congested, when flow required to have a clinical effect. reestablished Painful muscle cramps, White Infarcts (anemic): arterial respiratory insufficiency, occlusions or solid organs (heart, neurological sx. spleen, kidney). Pathophysiology: Formation of Micro: wedge-shaped, overlying gass bubbles within skeletal fibrinous exudate, margins better muscle, soft tissues and joints defined with time. causes pain. Focal ischemia to minutes to hours - usu no demonstrable brain and heart. changes o 12-18 hrs hemorrhage Micro: Pulmonary edema and o few hours to 1 -2 days - hemorrhage, focal atelectasis or inflammatory response, emphysema. Persistence of gas parenchymal regeneration emboli in the skeletal system leads to multiple foci of ischemic Factors That Influence Development of an necrosis (femoral head, tibia and Infarct: humerus). 1. vascular supply 2. rate of development of occlusion Amniotic Fluid Embolism (time for development of alternate Clinical: 1 in 50,000 deliveries. perfusion pathways) 80% mortality rate. Sudden 3. vulnerability of the tissue to severe dyspnea, cyanosis, and hypoxia (neurons 3-4 minutes, myocardium 20-30 minutes) 4. the blood oxygen content (e.g. Stages of Shock: ventilation) nonprogressive (compensated), progressive (widespread hypoxia), Shock irreversible Cardiogenic - myocardial pump failure o brain - ischemic Hypovolemic - loss of blood or plasma encephalopathy volume o heart - contraction band Septic - 25-75% mortality rate; 70% necrosis gram-negative bacilli. Endotoxins are o kidneys ATN LPS released when cell wall is degraded. o lungs DAD LPS directlt activates complement. o adrenal - cortical cell lipid Monocytes respond by producing TNF, depletion IL-1 fever and synthesis or acute phase o GI tract - patchy mucosal reactants. hemorrhages o systemic vasodilation o liver - fatty change, centilobular o dec. myocardial contractility necrosis o endothelial injury -> leukocyte adhesion -> ARDS Prognosis: varies with origin and duration. 80- o DIC 90% of young, healthy survive hypovolemic o Neurogenic - spinal cord injury, shock with management. 75% mortality for anesthesia cardiogenic shock with MI and gram negative o Anaphylactic - IgE mediated septic shock.