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Pathology Chapter 4 Robbins
Hemodynamic Disorder Final Complete
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How do normal hemodynamics work? - Blood circulates and delivers oxygen and nutrients and removes metabolic wastes from the cell without altering water and electrolyte balance What classify hemodynamic diseases? โ
- abnormal endothelial function
- increased vascular pressure
- decrease plasma protein alters water and electrolyte balance What is the outward movement of water into the extravascular space called? - Edema What is hemostasis? - Blood clotting that prevents excessive bleeding Abnormal hemostasis causes what 4 things: - hemorrhage low tissue perfusion Hypotension shock What is thrombosis? - The formation of abnormal blood clots What is embolism? - The migration of clots - obstruction of blood vessels, ischemia, and infarction What are three consequences of thromboembolism that lead to death? - MI Pulmonary embolism Cerebrovascular stroke What are two consequences of change in blood volume in a tissue? - Hyperemia (red) Congestion (blue) Hyperemia is an _______ process, while congestion is a ________ process - Active (arteriolar dilation and increased blood flow) Passive (impaired flow of venous blood in a tissue) What is an example of hyperemia? - Sites of inflammation or in exercising skeletal muscle. The increase in oxygenated blood causes the redness What are examples of congestion? - Systemic = cardiac failure Local = isolated venous obstruction in a tissue Blueness caused by deoxygenated blood (cyanosis)
What are 6 long term effects of chronic congestion? - Persistent hypoxia Parenchymal cell death Secondary tissue fibrosis Elevated intravascular pressure Edema Rupture capillaries=focal hemorrhages What are some signs of acute pulmonary congestion and edema? - Tissue are wet and ooze blood Blood-engorged alveolar capillaries Alveolar septal edema Intra-alveolar hemorrhage What are some consequences of chronic pulmonary congestion? - 1) Alveolar septa become thick and fibrotic
- Macrophages in alveolar spaces with hemosiderin (from phagocytosed red cells) What is centrizonal fibrosis? - A type of fibrosis in the lungs (chronic pulmonary congestion) What appearance can be seen with chronic passive congestion of the liver? - A nutmeg liver, due to central areas that are red and slightly depressed compared with the surrounding tan viable parenchyma What are some consequences of chronic passive congestion of the liver? - Centrilobular hepatic necrosis Hemorrhage Hemosiderin-laden macrophages Inflammatory cell migration What condition can develop from severe chronic passive congestion of the liver? - Hepatic fibrosis (cardiac cirrhosis) What percentage of our body is water? - 60% 2/3rds intracellular 1/3rd interstitial Only 5% is intravascular (in blood) What are 4 different types of edema? - Hydrothorax (pleural cavity) Hydropericardium (pericardial cavity) Hydroperitoneum ("Ascites") Anasarca (general, subcutaneous tissue) What are 3 factors that can influence fluid movement across capillary walls (edema)? -
- Increased hydrostatic pressure
What are examples of tumors that can cause lymphatic obstruction and edema? - Breast cancer. The finely pitted skin that appears is known as peau d'orange (orange peel skin) What is hemorrhage? - Extravasation of blood (loss of blood) from vessels causing hypovolemic shock Capillary bleeding can occur in ____________ ____________ tissues - Chronically congested What are 7 causes of hemorrhage? - Injury Clinical disorders Physical trauma Atherosclerosis Inflammatory erosion of vessel wall Neoplastic erosion of major vessel wall Weakening of vessel walls What is hemorrhagic diatheses (coagulopathies)? - A clinical disorder that causes hemorrhage What is a hematoma? - Blood within a tissue What is petechiae? - Low platelets small capillary leak What is a purpura? - A slightly larger (3-5mm) hemorrhage caused by trauma, vasculitis, and vascular fragility What is ecchymoses? - Larger (1-2cm) subcutaneous hematomas (bruises) where extravasated red cells are phagocytosed and degraded by macrophages What color is hemoglobin? bilirubin? hemosiderin? - Hemo = red Bili = blue-green Hemosid = golden brown What can CT scan show in regards to hematomas? MRI? - CT: The density of the hematoma MRI: Its chemistry and evolution (estimate time of hemorrhage) What is a subungual hematoma? - A bruise underneath the nail What is a petechiae? - A small capillary leak, leading to bleeding in the skin What 7 things cause petechiae? - Infection Allergic reaction
Medication Thrombocytopenia (low platelets) Defective platelet function Loss of vascular wall support Vitamin C deficiency Punctate petechial hemorrhages of the colonic mucosa is a consequence of _____________- - thrombocytopenia What is a purpura? - Large spots of bleeding under the skin Senile = old folks Bruises often move down the body in the direction of _______- - gravity What is a bleeding condition that can be fatal? - When blood leaks into body cavities such as in a fatal rupture of a dissecting aortic aneurysm, hemopericardium, hemoperitoneum, or hemarthrosis (joints) The clinical significance of a hemorrhage depends on the ________ of blood loss and the ________ of bleeding - volume rate What percent of blood loss do you need to have as an adult to experience hypovolemic shock? - > 20% Hemostasis is the opposite of _______________- - thrombosis. It preserves liquidity of blood, and plugs sites of vascular injury What are three general components of hemostasis? - Vascular wall (endothelium + ECM) Platelets Coagulation cascade What is the sequence of events following vascular injury? - Vasoconstriction Primary hemostasis Secondary hemostasis Thrombosis and antithrombotic events (Fibrin = polymerize, TPA limits plug) What causes vasoconstriction following vascular injury? - Reflex (neurogenic) Endothelin What is primary hemostasis? - Platelet adhesion and aggregation What causes secondary hemostasis? - Thrombin activation; fibrinogen to fibrin; fibrin deposition
WHere do the intrinsic and extrinsic pathways of clotting converge? - At factor Xa The _________clotting pathway is the most physiologically relevant pathway for coagulation after vascular damage - extrinsic. It is activated by tissue factor, a membrane bound glycoprotein expressed at sites of injury What does thrombin do in the presence of calcium? - Converts fibrinogen to insoluble fibrin What are the three primary abnormalities that lead to thrombus formation (Virchow's triad) - 1) Endothelial injury (most important)
- Stasis or turbulent blood flow
- Hypercoagulability of the blood Abnormalities of procoagulants or _____________ can tip the balance in favor of thrombosis - Anticoagulants _____________ form in the cardiac chambers following an MI - Thrombi What are some instances where thrombi will form over ulcerated plaques? - Atherosclerotic arteries Sites of traumatic vascular injury Inflammatory vascular injury (vasculitis) PGI2 inhibits ________________ activation - Platelets Following endothelial damage, synthesis and secretion of __________ is reduced - anticoagulants What are 7 ways in which endothelium can be damaged? - Hypertension Turbulent BF Bacterial products (LPS) Radiation injury Metabolic abnormalities Toxins (cigarette smoke) Allergies What are 3 metabolic abnormalities that lead to endothelial damage? - Homocystinuria (homocysteine is a procoagulant) Hyperhomocysteinemia Hypercholesterolemia What can blood flow abnormalities lead to, causing defects in clotting? - Turbulence Endothelial injury or dysfunction Countercurrents and local pockets of stasis
Arterial and cardiac thrombosis Normal blood flows in a __________ fashion - laminar, in the center of the vessel lumen What surrounds the blood cells and touches the endothelium? - Slow moving plasma How does stasis cause endothelial damage? - Platelets and leukocytes come in contact with the endothelium creating friction and denudation. It also slows the washout of clotting factors and impedes the inflow of clotting factor inhibitors Ulcerated atherosclerotic plaques expose __________ ECM - subendothelial Atherosclerotic plates can cause ____________ BF - turbulent Abnormal aortic and arterial dilations cause __________ which create local stasis and a fertile site for thrombosis - aneurysms Ventricular remodeling causes ___________- - aneurysms What kind of myocardium exists after an MI? - Focally non-contractile myocardium, because the myocytes are dead and are replaced by fibroblasts What causes a cardiac mural thrombus formation after MI? - 1) MI produces necrotic and inflammatory signals
- Infarcted ventricular wall is akinetic or dyskinetic (bulges outward during systole)
- Turbulent flow in the ventricle tends to form thrombi on the surface of the infarcted endocardium What are the sequence of events in cardiac mural thrombus formation? - 1) Platelets bind to damaged endocardium and release ADP, 5-HT, thromboxane and PF4/CXCL
- Platelets recruited/degranulated
- Thrombin activated (fibrin polymerization)
- Platelet-fibrin thrombus is now attached to inner cardiac wall What are 3 causes of cardiac thrombus? - Mitral valve stenosis Hyperviscosity syndrome (polycythemia) Sickle cell anemia What causes mitral valve stenosis? - Congenital After rheumatic heart disease What are 3 symptoms of mitral valve stenosis? - Left atrial dilation Atrial fibrillation Profound stasis and thrombi
What are 7 different types of emboli? - Thrombi Fat droplets Bubbles of air or nitrogen Atherosclerotic debris (cholesterol) Tumor fragments Bone marrow Amniotic fluid Fat-TABTAB What are some clinical consequences of embolism? - 1) Lodge in small vessels, partial or complete vascular occlusion Depending on its _____________, emboli can lodge anywhere in the vascular tree - origin What is the primary consequence of systemic embolization? - Ischemic necrosis (infarction) of downstream tissues What are 3 consequences of embolization in the pulmonary circulation? - Hypoxia Hypotension Right-side heart failure 95% of venous emboli are from deep ________ veins - leg. Depending on the size, it may lodge at pulmonary artery bifurcation (saddle embolus) or in the small arteries Most small pulmonary emboli are clinically ____________ - silent When does sudden death right heart failure (cor pulmonale) occur? - WHen > 60% of the pulmonary circulation is obstructed by emboli What percentage of systemic thromboemboli are from intracardiac mural thrombi? Aortic thrombi? - 80% 20% Embolization lodging sites are proportional to the degree of ___________ the organ gets - flow (cardiac output) What percentage of thromboemboli lodge in the lower extremities? The brain? - 75% 10% 15% = everywhere else What is a paradoxical thrombi? - A thrombus that travels from the venous side, but gets lodged in the left side of the heart or systemic circulation due to a septal defect in the atria or ventricles
Where does fat embolism syndrome (FES) originate? - Mostly from severe skeletal injuries (90%) from physical trauma or surgery that can block pulmonary arteries and veins, especially if the fracture mobilizes fatty bone marrow What 5 things can FES lead to? - Pulmonary insufficiency Respiratory failure Neurological symptoms Anemia (1-3 days post injury) Thrombocytopenia (1-3 days post injury) What is amniotic fluid emboli? - An uncommon (1 in 40,000), grave complication of labor in the immediate postpartum period caused by placental tears, or by fetal skin squamous cells that enter the maternal pulmonary microcirculation What is the mortality rate of mothers suffering from amniotic fluid emboli? - 80% What are 4 symptoms of amniotic fluid emboli? - Severe dyspnea, cyanosis Hypotensive shock Seizures/coma Pulmonary edema Disseminated intravascular coagulation (secondary to release of thrombogenic substances from amniotic fluid) What causes gas embolism in decompression sickness? - Sudden changes in atmospheric pressure (scuba divers, underwater workers, unpressurized aircraft) What 5 things do gas bubbles in the pulmonary vasculature cause? - Edema Hemorrhages Focal atelectasis (lung collapse) or emphysema The chokes (gas in pulmonary circulation) What is a chronic form of decompression sickness? - caisson disease (think scuba) What two surgeries can cause air embolisms? - Bypass surgery (coronary artery) Neurosurgery (cerebral artery) What causes an infarction (ischemic necrosis)? - Occlusion of either an arterial supply or venous drainage 99% of all infarcts result from ____________ episodes - thrombotic , and almost all result from arterial occlusion Where do red infarcts (hemorrhage) occur? - Venous occlusion, loose tissues, tissue with dual circulation, spongy organs like the lung Where do white infarcts occur (anemic)? - Arterial
What are consequences of hypotensive shock? - Impaired tissue perfusion, leading to cellular hypoxia What 5 conditions cause cardiogenic shock? - MI Ventricular rupture Arrhythmias Cardiac tamponade Pulmonary embolism When can hypovolemic shock occur? - Hemorrhage Fluid loss (vomiting, diarrhea, burns) = heat stroke What causes septic shock? - Overwhelming microbial infection Endotoxic shock Gram positive septicemia Fungal sepsis Superantigens What are the three stages of shock? - 1) Non-progressive. = reflex compensatory mechanisms activate, vital organs maintained 2 Progressive stage = tissue hypoperfusion. Onset of circulatory and metabolic imbalances including acidosis
- Irreversible stage tissue injury even if hemodynamic defects are fixed
