Hemodynamic Disorders and Thromboembolic Disease PDF

# Hemodynamic Disorders ## Overview - Edema (increased fluid in the ECF) - Hyperemia (INCREASED flow) - Congestion (INCREASED backup) - Hemorrhage (extravasation) - Hemostasis (opposite of thrombosis) - Thrombosis (clotting blood) - Embolism (downstream travel of a clot) - Infarction (death of tis...

# Hemodynamic Disorders ## Overview - Edema (increased fluid in the ECF) - Hyperemia (INCREASED flow) - Congestion (INCREASED backup) - Hemorrhage (extravasation) - Hemostasis (opposite of thrombosis) - Thrombosis (clotting blood) - Embolism (downstream travel of a clot) - Infarction (death of tissues w/o blood) - Shock (circulatory failure/collapse) ## Edema - **ONLY 4 POSSIBILITIES!!!** - Increased Hydrostatic Pressure - Reduced Oncotic Pressure - Lymphatic Obstruction - Sodium/Water Retention ## Water - 60% of body - 2/3 of body water is INTRA-cellular - The rest is INTERSTITIAL - Only 5% is INTRA-vascular - **EDEMA is SHIFT to the INTERSTITIAL SPACE** - **HYDRO** - THORAX, -PERICARDIUM, -PERITONEAL - **EFFUSIONS, ASCITES, ANASARCA** ## Increased Hydrostatic Pressure - Impaired venous return - Congestive heart failure - Constrictive pericarditis - Ascites (liver cirrhosis) - Venous obstruction or compression - Thrombosis - External pressure (e.g., mass) - Lower extremity inactivity with prolonged dependency - Arteriolar dilation - Heat - Neurohumoral dysregulation ## Reduced Plasma Oncotic Pressure (Hypoproteinemia) - Protein-losing glomerulopathies (nephrotic syndrome) - Liver cirrhosis (ascites) - Malnutrition - Protein-losing gastroenteropathy ## Lymphatic Obstruction (Lymphedema) - Inflammatory - Neoplastic - Postsurgical - Postirradiation ## Na+ RETENTION - Excessive salt intake with renal insufficiency - Increased tubular reabsorption of sodium - Renal hypoperfusion --> Increased renin-angiotensin-aldosterone secretion ## Inflammation - Acute inflammation - Chronic inflammation - Angiogenesis ## CHF Edema - INCREASED VENOUS PRESSURE DUE TO FAILURE - DECREASED RENAL PERFUSION, triggering of RENIN-ANGIOTENSION-ALDOSTERONE complex, resulting ultimately in SODIUM RETENTION ## Hepatic Ascites - PORTAL HYPERTENSION - HYPOALBUMINEMIA ## Renal Edema - SODIUM RETENTION - PROTEIN LOSING GLOMERULOPATHIES (NEPHROTIC SYNDROME) ## Edema - SUBCUTANEOUS ("PITTING") - "DEPENDENT" - ANASARCA - LEFT vs RIGHT HEART - PERIORBITAL - PULMONARY - CEREBRAL (closed cavity, no expansion) - HERNIATION of cerebellar tonsils - HERNIATION of hippocampal uncus over tentorium - HERNIATION, subfalcine ## "Pitting" Edema A diagram of a human leg with pitting edema. ## Transudate vs Exudate - **Transudate** - results from disturbance of Starling forces - specific gravity < 1.012 - protein content < 3 g/dl, LDH LOW - **Exudate** - results from damage to the capillary wall - specific gravity > 1.012 - protein content > 3 g/dl, LDH HIGH ## Hyperemia/(Congestion) A diagram that compares normal blood flow through a capillary bed with hyperemia (INCREASED inflow) and congestion (Decreased outflow). - **NORMAL** - **HYPEREMIA** _erythema_ - Increased inflow (e.g., exercise, inflammation) - **CONGESTION** _cyanosis/hypoxia_ - Decreased outflow (e.g., local obstruction, congestive heart failure) ## Hyperemia - Active Process ## Congestion - Passive Process - Acute or Chronic ## Acute Passive Hyperemia/Congestion, Lung A diagram of lung tissue affected by acute passive hyperemia/congestion. ## Kerley B lines A chest x-ray image showing Kerley B lines, which are indicative of alveolar edema. ## The CXR in Left Ventricular Failure An illustration comparing a normal chest x-ray with the typical appearance of a chest x-ray in left ventricular failure, highlighting alveolar edema, Kerley B lines and pleural effusion. ## Chronic Passive Hyperemia/Congestion, Lung Micrograph of lung tissue affected by chronic passive hyperemia/congestion. ## Acute Passive Congestion, Liver Micrograph of liver tissue affected by acute passive congestion. ## Chronic Passive Hyperemia/Congestion, Liver A comparison of macroscopic and microscopic views of a liver affected by chronic passive Hyperemia/congestion. ## Subfalcine, Transtentorial and Tonsillar Herniation An illustration of a cross section of the brain showing subfalcine, transtentorial and tonsillar herniation. ## Hemorrhage - EXTRAVASATON beyond vessel - "HEMORRHAGIC DIATHESIS" - HEMATOMA (implies MASS effect) - "DISSECTION" - PETECHIAE (1-2mm) (PLATELETS) - PURPURA <1cm - ECCHYMOSES >1cm (BRUISE) - HEMO-: - thorax, -pericardium, -peritoneum, HEMARTHROSIS - ACUTE, CHRONIC ## Evolution of Hemorrhage - ACUTE-->CHRONIC - PURPLE-->GREEN-->BROWN - HGB-->BILIRUBIN-->HEMOSIDERIN ## Hematoma vs "Clot" ## Hemostasis - OPPOSITE of THROMBOSIS - PRESERVE LIQUIDITY OF BLOOD - "PLUG" sites of vascular injury - THREE COMPONENTS - VASCULAR WALL, i.e., endoth/ECM - PLATELETS - COAGULATION CASCADE ## Sequence of Events following Vascular Injury - ARTERIOLAR VASOCONSTRICTION - Reflex Neurogenic - Endothelin, from endothelial cells - THROMBOGENIC ECM at injury site - Adhere and activate platelets - Platelet aggregation (1° HEMOSTASIS) - TISSUE FACTOR released by endothelium, plats. - Activates coagulation cascade--> thrombin--> fibrin (2° HEMOSTASIS) - FIBRIN polymerizes, TPA limits plug ## Players - ENDOTHELIUM - PLATELETS - COAGULATION "CASCADE" ## Endothelium - NORMMALLY - ANTIPLATELET PROPERTIES - ANTICOAGULANT PROPERTIES - FIBRINOLYTIC PROPERTIES - IN INJURY - PRO-COAGULANT PROPERTIES ## Endothelium - ANTI-Platelet Properties - Protection from the subendothelial ECM - Degrades ADP (inhib. Aggregation) - ANTI-Coagulant Properties - Membrane HEPARIN-like molecules - Makes THROMBOMODULIN--> Protein-C - TISSUE FACTOR PATHWAY INHIBITOR - FIBRINOLYTIC PROPERTIES (TPA) ## Endothelium - PROTHROMBOTIC PROPERTIES - Makes vWF, which binds Plats--> Coll - Makes TISSUE FACTOR (with plats) - Makes Plasminogen inhibitors ## Endothelium - ACTIVATED by INFECTIOUS AGENTS - ACTIVATED by HEMODYNAMICS - ACTIVATED by PLASMA - ACTIVATED by ANYTHING which disrupts it ## Platelets - ALPHA GRANULES - Fibrinogen - Fibronectin - Factor-V, Factor-VIII - Platelet factor 4, TGF-beta - DELTA GRANULES (DENSE BODIES) - ADP/ATP, Ca+, Histamine, Serotonin, Epineph. - With endothelium, form TISSUE FACTOR ## Platelet Phases - ADHESION - SECRETION (i.e., "release" or "activation" or "degranulation") - AGGREGATION ## Platelet Adhesion - Primarily to the subendothelial ECM - Regulated by VWF, which bridges platelet surface receptors to ECM collagen ## Platelet Secretion - BOTH granules, a and δ - Binding of agonists to platelet surface receptors AND intracellular protein PHOSPHORYLATION ## Platelet Aggregation - ADP - TxA2 (Thromboxane A2) - THROMBIN from coagulation cascade also - FIBRIN further strengthens and hardens and contracts the platelet plug ## Coagulation "CASCADE" - INTRINSIC(contact)/EXTRINSIC(TissFac) - Proenzymes-->Enzymes - Prothrombin(II)--> Thrombin(lla) - Fibrinogen(I)-->Fibrin(la) - Cofactors - Ca++ - Phospholipid (from platelet membranes) - Vit-K dep. factors: II, VII, IX, X, Prot. S, C, Z ## Coagulation Tests - (a)PTT _INTRINSIC_ (HEP Rx) - PT (INR) _EXTRINSIC_ (COUM Rx) - BLEEDING TIME (PLATS) (2-9min) - Platelet count (150,000-400,000/mm3) - Fibrinogen - Factor assays ## Thrombosis - Pathogenesis - Endothelial Injury - Alterations in Flow - Hypercoagulability - Morphology - Fate - Clinical Correlations - Venous - Arterial (Mural) ## Virchow's Triangle A diagram of a triangle that represents the 3 main factors involved in thrombosis; Endothelial Injury, Abnormal Flow (Non-Laminar), and Hypercoagulation. ## Endothelial "Injury" - Jekyll/Hyde disruption - any perturbation in the dynamic balance of the pro- and antithrombotic effects of endothelium, not only physical "damage" ## Thrombosis - Virchow's TRIANGLE - ENDOTHELIAL INJURY - ABNORMAL FLOW (NON-LAMINAR) - HYPER-COAGULATION ## Abnormal Flow - NON-LAMINAR FLOW - TURBULENCE - EDDIES - STASIS - "DISRUPTED" ENDOTHELIUM - ALL of these factors may bring platelets into contact with endothelium and/or ECF ## Hypercoagulability (Inherited) - COMMONEST: Factor V and Prothrombin defects - Common: Mutation in prothrombin gene, Mutation in methylenetetrahydrofolate gene - Rare: Antithrombin III deficiency, Protein C deficiency, Protein S deficiency - Very rare: Fibrinolysis defects ## Hypercoagulability (Acquired) - Prolonged bed rest or immobilization - Myocardial infarction - Atrial fibrillation - Tissue damage (surgery, fracture, burns) - Cancer (TROUSSEAU syndrome, i.e., migratory thrombophlebitis) - Prosthetic cardiac valves - Disseminated intravascular coagulation - Heparin-induced thrombocytopenia - Antiphospholipid antibody syndrome (lupus anticoagulant syndrome) - **Lower risk for thrombosis:** - Cardiomyopathy - Nephrotic syndrome - Hyperestrogenic states (pregnancy) - Oral contraceptive use - Sickle cell anemia - Smoking, Obesity ## Morphology - ADHERENCE TO VESSEL WALL - HEART (MURAL) - ARTERY (OCCLUSIVE/INFARCT) - VEIN - OBSTRUCTIVE vs. NON-OBSTRUCTIVE - RED, YELLOW, GREY/WHITE - ACUTE, ORGANIZING, OLD ## Mural Thrombi, Heart A photo of a heart with a mural thrombi. ## Fate of Thrombi - PROPAGATION (Downstream) - EMBOLIZATION - DISSOLUTION - ORGANIZATION - RECANALIZATION ## Fate of Thrombi A diagram of a thrombus in a vein showing the different possible fates of a thrombus; resolution, embolization to lungs, organization and incorporation into the wall, and organization and recanalization. ## Occlusive Arterial Thrombus A photo of a cross section of an artery showing an occlusive arterial thrombus. ## DVT - D. (CALF, THIGH, PELVIC) V.T. - CHF a huge factor - **INACTIVITY!!!** - Trauma - Surgery - Burns - Injury to vessels - Procoagulant substances from tissues - Reduced t-PA activity ## Arterial/Cardiac Thrombi - ACUTE MYOCARDIAL INFARCTION = OLD ATHEROSCLEROSIS + FRESH THROMBOSIS - ARTERIAL THROMBI also may send fragments DOWNSTREAM, but these fragments may contain flecks of calcified or cholesterol PLAQUE also - LODGING is PROPORTIONAL to the % of cardiac output the organ receives i.e., brain, kidneys, spleen, legs, or the diameter of the downstream vessel ## Ateroemboli - "CHOLESTEROL" clefts are components of atherosclerotic arterial plaques, NOT venous thrombi!!! ## Disseminated Intravascular Coagulation - **D.I.C.** (Shock and DIC are joined at the hip) - OBSTETRIC COMPLICATIONS - ADVANCED MALIGNANCY - SHOCK - NOT a primary disease - CONSUMPTIVE coagulopathy, e.g., reduced platelets, fibrinogen, F-VIII and other consumable clotting factors, brain, heart, lungs, kidneys, MICROSCOPIC ONLY ## Embolism - Pulmonary - Systemic (Mural Thrombi and Aneurysms) - Fat - Air - Amniotic Fluid ## Pulmonary Embolism - USUALLY SILENT, USUALLY SILENT - CHEST PAIN, LOW PO2, S.O.B. - Sudden OCCLUSION of >60% of pulmonary vasculature, presents a HIGH risk for sudden death, i.e., acute cor pulmonale, ACUTE right heart failure - "SADDLE" embolism often/usually fatal - PRE vs. POST mortem blood clot: - PRE: Friable, adherent, lines of "ZAHN" - POST: Current jelly or chicken fat ## Systemic Emboli - "PARADOXICAL" EMBOLI - 80% cardiac/20% aortic - Embolization lodging site is proportional to the degree of flow (cardiac output) that area or organ gets, i.e., brain (15%), kidneys (~25%), legs, splanchnic (~25%), liver (~25%) ## Other Emboli - FAT (long bone fx's, also bones with marrow) - AIR (SCUBA "bends") - AMNIOTIC FLUID, very prolonged or difficult delivery, high mortality ## Amniotic Fluid Embolism A micrograph of lung tissue showing amniotic fluid embolism. ## Infarction - Defined as an area of necrosis* secondary to decreased blood flow - HEMORRHAGIC vs. ANEMIC - RED vs. WHITE - END ARTERIES vs. DUAL ARTERY SUPPLY - ACUTE-->ORGANIZATION-->FIBROSIS ## Infarction Factors - **NATURE of VASCULAR SUPPLY** - Single end arteries such as kidney, spleen? - Dual blood supply such as lung, liver? - **RATE of DEVELOPMENT** - SLOW (BETTER) - FAST (WORSE) - **VULNERABILITY to HYPOXIA** - MYOCYTE vs. FIBROBLAST ## Shock - Pathogenesis - Cardiac - Septic - Hypovolemic - Morphology - Clinical Course ## Shock - **Definition:** CARDIOVASCULAR COLLAPSE - **Common pathophysiologic features:** - INADEQUATE CARDIAC OUTPUT and/or - INADEQUATE BLOOD VOLUME