Ex2_Path

How is transudate produced? How is exudate produced? Give characteristics of fluid and examples of causes.
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How is transudate produced? How is exudate produced? Give characteristics of fluid and examples of causes.
Transudate:
- Systemic forces produce an effusion via changes in starling forces (oncotic, hydrostatic pressures)
- Protein poor, low specific gravity, no inflammatory cells, LDH low
- Left ventricular failure, pulmonary congestion, renal failure, liver failure, cirrhosis

Exudate:
- Inflammation produces an effusion via changes in vascular permeability, absorption or production of pleural fluid; damage to capillary wall
- Protein high, high specific gravity, inflammatory cells, LDH high
- Bacterial pneumonia, viral infection, cancer, pulmonary embellism
What are 2 histological characteristics of chronic passive pulmonary congestion?
1. macrophages with hemosiderin - capillary rupture
2. thickened alveolar septa - collagen deposition; fibrotic
What are 2 histological characteristics of chronic passive hepatic congestion?
1. centrilobular hepatic necrosis; hemorrhage
2. pericentral hepatocyte atrophy and sinusoidal distension

(nutmeg liver)
What are the 3 histological characteristics of granulation tissue?
1. plump fibroblasts
2. loose ground substance
3. dilated capillaries
What 3 things accumulate in artherosclerosis?

Cholesterol accumulates in which 2 cells?

Where in the body is artherosclerosis found in?
1. cholesterol (& cholesterol esters)
2. collagen (fibrous tissue)
3. calcifications

1. smooth muscle cells
2. macrophages

- In the intimal layer of large arteries
What are 3 causes to arterial thrombosis?

How do these causes affect the arterial?

What can be seen in gross?
1. artherosclerosis
2. vasculitis
3. trauma

- Endothelial damage

- Pale grey fibrin strands
What are the causes for venous thrombosis?
- Stasis, immobilization
- Sluggishness of blood flow
- Congestive heart failure
What are the 4 fates of thrombi?

Which one is most clinically significant for arterial thrombosis? For venous thrombosis?
1. propagation
2. embolism
3. dissolution
4. organization and recanalization

- Propagation can lead to luminal obstruction and then infarction
- Embolism can reach pulmonary circulation
What is the difference between red and pale infarcts? Examples?
Red:
- Ischemia causes necrosis of tissue
- Dual blood supply allows hemorrhage into necrotic tissue
- Lung, GI

Pale:
- Compact tissue absent with collateral circulation
- Heart, spleen, kidney
How and when does pulmonary thromboembolism cause sudden death?
If more than 60% of the pulmonary circulation is obstructed by emboli, the patient is at a high risk of sudden death due to acute right heart failure (cor pulmonale) or shock (cardiovascular collapse).
What is a fat embolism? What are they made of?- Fat embolism occurs after fractures of long bones, major soft tissue trauma, or severe burns - Consists of fat or marrow particles.What is amniotic fluid embolism?- Pulmonary vessels contain squamous cells and mucin (contents of amniotic fluid) derived from fetal skin and intestinal tract. - Mortality in 80% due to respiratory insufficiency, shock, DIC, seizures, and comaWhat are the major morphologic changes in multiple organ failure in a patient who dies of shock?Kidneys: Acute tubular necrosis. Brain: Laminar cortical necrosis. Lungs: Shock lung (diffuse alveolar damage) with hyaline membranes (seen mainly in septic shock). Heart: Foci of necrosis, hemorrhage, contraction band necrosis. GI: Hemorrhages. Liver: Central hemorrhagic necrosis, fatty change.Which molecule converts fibrinogen into fibrin and fibrinopeptides? What do fibrinopeptides do?-Thrombin (pro-coagulation) 1. Increase vascular permeability 2. Chemotaxis for leukocytesWhich molecule activates complement C3, C5; splits fibrin into split products; converts/activates factor XIIa; cleaves V and VIII? What do fibrin split products do?- Plasmin (anti-coagulation) - Increase vascular permeability - Inhibition of thrombin, platelet aggregation, and fibrin polymerizationWhat happens during the adhesion phase of thrombogenesis?- Vessel injury exposes subendothelial collagen - vWF is exposed - Platelets bind to vWF via glycoprotein receptors (IIb/IIIa)What 3 things do platelets release after adhesion in thrombogenesis via granules? What molecule is created when platelet membrane phospholipase is activated? What 2 things does it do?1. ADP - platelet aggregation 2. histamine, serotonin - vasodilation, vascular permeability 3. PDGF - endothelial repair - Thromboxane A2 (TxA2) via arachidonic acid 1. Vasoconstriction 2. Platelet aggregationWhat are the 4 functions of platelets?1. Platelet plug formation 2. Repair endothelium (PDGF) 3. Maintain vascular endothelium 4. Forming platelet-phospholipid complexes (coagulation cascade)How do platelets activate the coagulation cascade?- After adhesion platelets change conformation - Platelet phospholipid complex is revealed - Promotes coagulation cascadeWhat are the 6 molecules that promote platelet aggregation?1. ADP 2. thrombin 3. Thromboxane A2 (TxA2) 4. collagen 5. epinephrine 4. PAFWhat 6 things inhibit platelet aggregation?1. Fibrin split products 2. PGI2 (prostacyclin synthesis antagonises thromboxanes synthesis) 3. COX inhibitors (aspirin) 4. ADP receptor antagonists 5. Phosphodiesterase inhibitors 6. Glycoprotein (IIb/IIIa) receptor antagonistsWhat are the 4 functions of endothelial cells?1. Thromboresistance 2. Vascular repair 3. Barrier 4. Metabolic transfersWhat are the 7 ways endothelial cells are thromboresistant?1. Produces heparin-like molecules (antithrombin III) 2. Produces thrombomodulin (APC) 3. Produces PGI2 and NO 4. Produces protein S (APC) 5. Activates plasminogen 6. Inactivates thrombin (antithrombin III) 7. Degrades ADPHow do endothelial cells activate antithrombin III ? What does antithrombin III do?- They produce heparin-like molecules on surface that activate antithrombin III - It cleaves thrombin, factors IXa, and Xa; inhibiting coagulationHow do endothelial cells activate protein C (APC)?- They produce thrombomodulin - This endothelial cell surface protein converts thrombin into an activator of APC - APC cleaves Va and VIIIa; inhibiting coagulationWhat does APC do? Which 2 molecules activate it?- APC cleaves Va and VIIIa; inhibiting coagulation - Helps reduce mortality by sepsis - Helps reduce LPS effects - Anti-inflammatory, pro-fibrinolytic - Inhibits TNFa production 1. thrombomodulin/thrombin 2. protein SWhat are the 2 ways endothelial cells affect thrombin in anticoagulation?1. Heparin-like molecules activate antithrombin III which cleaves thrombin and coagulation factors 2. Thrombomodulin transforms thrombin to activate APC, which cleaves coagulate factorsWhat 5 things happen when the endothelial is disrupted?1. Exposing collagen and vWF causes platelet adhesion 2. Platelets release ADP (platelet aggregation) and produce TxA2 (vasoconstriction and platelet aggregation) 3. Platelet phospholipid complex exposure (intrinsic path coagulation) 4. Tissue factor is released (extrinsic path coagulation) 5. Fibrinolysis (modulating coagulation)How is the extrinsic pathway of coagulation activated?- Tissue factor binds to factor 7 and activates it - TF:7a activates factor 10 - 10a converts prothrombin to thrombin - Thrombin cleaves fibrinogen into fibrin TF + 7 activates 10How is the intrinsic pathway of coagulation activated?- After adhesion platelets change conformation to reveal platelet phospholipid complexes - This phospholipid complex activates factor 9 - 9a binds to factor 8a - 9a:8a activates factor 10 - 10a converts prothrombin to thrombin - Thrombin cleaves fibrinogen into fibrin 9 + 8 activates 10Prothrombin time (PT) measures which pathway? Which factor is mostly likely defected? Partial prothrombin time (APTT) measures which pathway? Which factor is mostly likely defected?- Extrinsic pathway - factor 7 - 12 seconds for clot - Intrinsic pathway - factor 8 (classic hemophilia) - 25 second for clotWhich factor links the kinin, coagulation, plasminogen, and complement systems together?- Factor XII (Hageman Factor) Kinin - pain, vasodilation, vascular permeability Coagulation - thrombogenesis Plasminogen - fibrinolysis Complement - inflammation, anaphylatoxins, opsonin; lysis of cellsWhat are the 4 disorders of hemostasis?1. Hereditary thrombophilia - (prothrombotic) 2. Lupus anticoagulant - (prothrombotic) 3. DIC - (pro and antithrombotic) 5. HIT syndrome - (pro and antithrombotic)What are the 4 causes for hereditary thrombophilia?1. Factor V Leiden 2. Prothrombin 20210A transition (mutation) 3. MTHFR (C677T) mutation 4. Deficiencies in antithrombotic proteins (antithrombin III, protein S, protein C/APC)What is factor V Leiden?- Produces hereditary thrombophilia - Mutated factor V protein makes it resistant to cleavage/inactivation by APC - Most common cause of thrombophiliaWhat is prothrombin 20210A transition (mutation)?- Produces hereditary thrombophilia - Mutation elevates prothrombin levels - Second most common cause of thrombophiliaWhat does MTHFR (C677T) mutation do?- Produces hereditary thrombophilia - Mutation elevates homocysteine levelsWhat is lupus anticoagulant and how is it related to APTT?- Prolonged partial prothrombin time (which makes it look anticoagulant) BUT: - It is actually a prothrombotic disorder - Autoantibodies against proteins complexed phospholipidsWhat is DIC (disseminated intravascular coagulation)? What do tests reveal?- Pro-thrombic and anti-thrombotic disorder - Widespread thrombosis and hemorrhage - Consumption of platelets and coagulation factors - Widespread deposition of fibrin - Prolonged PTT, APTT, thrombin timeWhat are the most common causes of DIC?- Pregnancy complications - Malignancy - Sepsis (gram negative) - Major traumaWhat are the common morphologic changes seen in DIC (disseminated intravascular coagulation)?- Microthrombi in many organs - brain, heart, lungs, kidney - Microinfarcts in kidney, brain, etc - Hyaline membranes in lungs - Adrenal hemorrhage in meningococcemia (Waterhouse-Friderichsen syndrome) - Necrosis of the pituitary gland (Sheehan syndrome) - Fragmented red cells and thrombocytopenia on the blood smearWhat is the main pathology of DIC (disseminated intravascular coagulation)? How dose is affect the body?- Release of tissue factor and endothelial injury - Bacterial endotoxins promote increased synthesis and release of tissue factor (thromboplastin) from monocytes - (Activated monocytes also release IL-1 and TNF; increases expression of tissue factor on endothelial cells; while decreasing the expression of thrombomodulin on endothelial cells) - Increased tissue factor (thromboplastin) activates the clotting system. Lowered thrombomodulin levels decrease APC - Thus, there is simultaneous activation of the clotting system and inhibition of coagulation control, leading to the formation of widespread microthrombi.What is HIT syndrome?- Heparin-induced thrombocytopenia - Antibodies complex with high-molecular-weight heparin and platelet factor 4 - Pro and antithromboticDo you have more water intracellularly or extracellularly?- Body is 60% water: - 1/3 extracellularly - 2/3 intracellularlyWhat are the 4 causes of edema?1. Increased hydrostatic pressure 2. Decreased oncotic pressure 3. Lymphatic obstruction 4. Sodium and water retentionImpaired venous return can increase hydrostatic pressure leading to edema. What are 4 causes of this?1. Constrictive pericarditis 2. Congestive heart failure 3. Ascites (hydroperitoneum) 4. Venous obstruction or lower extremity stasisDecreased oncotic pressure can lead to edema. What are 4 causes of this?1. Glomerulopathies - leaks; loss of albumin 2. Liver cirrhosis - reduced albumin synthesis 3. Malnutrition 4. Protein losing gastroenteropathyLymphatic obstruction can lead to edema. What are 4 causes of this? 2 examples?1. Inflammatory 2. Neoplastic 3. Postsurgical 4. Postirradiation 1. Filiariasis - elephantiasis 2. Irradiation of breast/axilla can cause edema (mom)Sodium and water retention can lead to edema. What are 3 causes of this?1. Excessive water intake and renal insufficiency 2. Increased tubular reabsorption of sodium 3. Oliguria (low output of urine)These types of edema are caused by what? - Peripheral edema - Pulmonary edema - Brain edemaPeripheral edema - cardiac disease, renal disease Pulmonary edema - left ventricular failure, renal failure, acute respiratory distress syndrome, pulmonary infection Brain edema - brainstem herniation, vascular obstructionWhat is hyperemia? Examples?- active process of arteriolar dilation - increased blood flow - inflammation, muscle during exerciseWhat is congestion? Examples?- passive process of reduced outflow of blood - cardiac failure, venous obstruction, stasisWhat is hemorrhage? What are some causes?- extravasation of blood into extravascular space - trauma, vascular injury, artherosclerosis neoplastic, or inflammatory erosion of vessel wallHow big are petechia? Purpura? Eccymosis?1-2mm - petechia >3mm - purpura >1-2 cm: - ecchymosisIn an ecchymosis the color transforms from red-blue to blue-green to gold-brown. Why?Hemoglobin is converted into bilirubin and then into hemosiderin.What is shock? How does this lead to cell injury?- Systemic hypotension due to decreased cardiac output or reduced effective circulating blood volume - Cellular injury comes from impaired tissue perfusion and cellular hypoxiaWhat are the 3 causes of shock? Examples.1. Cardiogenic shock - low cardiac output due to myocardial pump failure - MI, ventricular arrythmia, cardiac tamponade, pulmonary embolism 2. Hypovolemic shock - low cardiac output due to loss of blood or plasma volume - massive hemorrhage, fluid loss from severe burns 3. Septic shock - vasodilation and peripheral pooling of blood due to systemic immune reaction to bacteria or fungiWhat is the order of most likely cause of septi shock? (3 things)1. gram-positive bacteria 2. gram-negative bacteria 3. fungiHow does septic shock lead to a hypercoagulable state?- Bacteria walls and endotoxins induce a cytokine cascade (IL-1, IL-6, IL-8, TNF) - Complement and kinin systems cause direct toxic injury to cells - Endothelial injury leads to activation of coagulation pathways (tissue factor) and to DIC - Vasodilation leads to hypovolemiaWhat metabolic characteristics does septic shock have?- Insulin resistance and hyperglycemia (IL-1, TNF, glucocorticoids) - Insulin resistance and inhibited insulin release (cytoines impairing GLUT-4) - Suppressed bactericidal activity (hyperglycemia) - Adrenal insufficiencyWhat is an example of a superantigen producing septic shock?- toxic shock syndrome from - Staphylococcus aureusWhat are the 3 stages of shock?1. Nonprogressive stage - tachycardia and peripheral vasoconstriction, renal conservation of fluid; vital organ perfusion maintained 2. Progressive stage - tissue hypoperfusion; circulatory and metabolic imbalance; metabolic acidosis, lactic acidosis 4. Irreversible stage - organ damage; surival not possible; renal shutdownWhat are the morphological manifestations of septic shock?1. Acute tubular necrosis 2. DIC - fibrin rich microthrombi 3. Mucosal hemorrhages in colon 4. Depletion of lipid in adrenal cortex 5. Pulmonary edema 6. Centrilobular necrosis of liver; fatty change 7. Brain necrosisWhat is anaphylactic shock?- IgE-mediate hypersensitivity - Systemic vasodilation and increased vascular permeability - Hypoxia, hypoperfusionAdenocarcinoma- malignant tumor of glandular epithelium - Polyps - ColonAdenoma- benign tumor of glandular epithelium - PolypsMalignant- Invasion, metastasis - Poorly differentiated (loss of function) - Pleomorphism (irregular size and shape of cell/nucleus) - Hyperchromatism (dark nuclei) - Increased nuclear-cytoplasmic ratio - Large, prominent nuclei - Abnormal mitoses - Disordered architecture, disorganized - Irregular border - High cellularity - To liverBenign- Well differentiated - Closely resembles tissue of origin - Tend to be encapsulatedFibroadenoma- Connective tissue proliferation surrounding adenoma (benign glandular epithelium) - Fibroadenoma of breast - Round, bordered, white, firmDesmoplasia- Fibrous connective tissue proliferation induced by an adenocarcinoma (malignant glandular epithelium) - Especially from breast, pancreas, prostate adenocarcinomas