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Path Chapter 4


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What is "anasarca"
severe, generalized edema with profound subcutaneous tissue swelling
Which one is protein rich: exudate or transudate?
What conditions are exudate associated with?
What conditions are transudate associated with?
Cardiac failure
What causes generalized increases in venous pressure?
Right ventricular heart failure
What are the clinical signs of increased venous pressure?
systemic edema & reduced renal perfusion --> Na+ retention via RAS
What serum protein is most responsible for maintaining plasma osmotic pressure?
What is nephrotic syndrome?
Leaky glomerular capillaries which lead to proteinuria.
What are clinical signs of nephrotic syndrome?
↓ oncotic pressure → edema → ↓ intravascular volume → RAS activation → Na+ retention → exacerbation of edema
What is "filariasis"?
parasitic infection → lymphatic/lymph node fibrosis in inguinal region → elephantiasis
What do poststreptococcal glomerulonephritis or acute renal failure lead to?
Salt retention
Describe the localizations of edema due to cardiac failure?
localized to "dependent body parts" (i.e. legs when standing, buttocks when sitting)
Describe the localization of edema due to renal dysfunction/nephrotic syndrome?
affects all parts equally, initially manifests in areas with loose connective tissue (i.e. eyelids- periorbital edema)
What do hyperemia and congestion indicate?
Local increases in blood volume in a particular tissue
What is hyperemia?
1) increased blood flow
2) active process
3) due to arterial dilation
4) tissue becomes red due to engorgement with blood
What is congestion?
1)impaired venous return from tissue
2) passive process
3) can be systemic (heart failure) or localized (venous obstruction)
4) tissue becomes blue-red color due to cyanosis (deoxygenated hemoglobin)
What are the 5 categories that cause edema?
1) increased hydrostatic pressure
2) reduced osmotic pressure
3) lymphatic obstruction
4) sodium retention
5) inflammation
What are the common causes of increased hydrostatic pressure leading to edema?
Impaired venous return
1) CHF
2) constrictive pericarditis
3) ascites (liver cirrhosis)
4) venous obstruction
Arterioular dilation
1) heat
2) neurohumoral dysregulation
What are the common causes of reduced plasma osmotic pressure leading to edema?
1) protein losing gomerulopathies
2) liver cirrhosis (ascites)
3) malnutrition
4) protein-losing gastroenterophaty
What are the common causes of lymphatic obstruction leading to edema?
1) inflammatory
2) neoplastic
3) post-surgical
4) postirradiation
What are the common causes of sodium retention leading to edema?
1) excessive salt intake w/ renal insuffiency
2) increased tubular reabsorption of sodium
3) renal hypoperfusion
4) increased RAS activity
What are the common causes of inflammation leading to edema?
1) acute inflammation
2) chronic inflammation
3) angiogenesis
What are the morphological characteristics of acute pulmonary congestion?
1)characterized by alveolar capillaries engorged with blood
2) focal intra-alveolar hemorrhage
3) common with left ventricular heart failure
What are the morphological characteristics of acute hepatic congestion?
1) central vein and sinusoids become distended with blood
2) central hepatocyte degeneration
3) periportal hepatocytes may undergo fatty change due to less severe damage (due to closer proximity to
hepatic artery)
4) commonly due to right ventricular heart failure
What are the morphological characteristics of acute congestion?
1) vessels are distended
2) organs are grossly hperemic
3) interstitial edema due to capillary congestion
What are the morphological characteristics of chronic congestion?
1) focal hemorrhage caused by capillary rupture
2) hemosidern-laden macrophages
3)parenchymal atrophy/fibrosis (gives shrunken brown appearance)
What are the morphological haracteristics of chronic pulmonary congestion?
1)chronic- sepat become thickened and firbrotic
2)alveolar spaces may contain hemosiderin -laden macrophages ("heart failure cells")
What is "cardiac cirrhosis"?
hepatic fibrosis from longstanding hepatic congestion due to right ventricular heart failure.
What are hemorrhagic diatheses?
A group of disorders characterized by the tendancy to hemorrhage from insignificant injuries.
What is a hematoma?
Hemorrhage enclosed tissue
What kind of hematoma would a ruptured aortic aneurysm cause?
"retroperitoneal hematoma"
List the types of hemorrhages from smallest to largest.
1) petechiae
2) purpura
3) ecchymoses
4) hemothorax, hemopericardium...etc
What are common causes of petechiae?
1) associated with locally increased intravascular pressure
2)low platelet count (thrombocytopenia)
3) defective plately function
4) clotting factor deficinecies
What is "thrombocytopenia"?
Low platelet count
What are common causes of purpura?
1) same causes as petechia
2) trauma
3) vascular inflammation (vasculitis)
What is vasculitis?
vascular inflammation
What are common names for ecchymoses?
bruises/subcutaneous hematoma
What are common characteristics of ecchymoses?
1) erythrocytes are degraded and phagocytosed by macrophages
2) hemoglobin is converted to bilirubin and eventually to hemosiderin (color changes)
What is the color of hemoglobin?
What is the color of bilirubin?
What is the color of hemosiderin?
What do hemothoraxes and other large accumulations of blood cause?
What is hemorrhagic shock?
Shock due to hypovolemia
What is the advantage of internal bleeding vs. external bleeding?
Iron can be reused in internal bleeding.
What is primary hemostasis?
platelet aggregation
What is secondary hemostasis?
coagulation cascade
What are the sequence of events at a site of vascular injury?
1) reflex neurogenic arteriolar vasoconstriction via endothelin
2)platelet adhesion and activation to form temporary hemostatic plug
3) activation of the coagulation cascade (driven by "tissue factor")
4)activation of counter -regulatory mechanisms to control clotting
What is the function of "tissue factor"?
a membrane-bound procoagulant factor synthesized by endothelium that activates thrombin
What are the steps in the coagulation cascade?
1) activation of thrombin
2) thrombin cleaves fibrinogen to fibrin
3) thrombin also induces platelet recuirtment and granule release
What is the function of tissue-plasminogen activator?
A counter regulatory factor that limits the hemostatic plug to the site of injury.
What are the 3 anti-thrombotic properties of endothelium?
1) anti-platelet effects
2) anti-coagulant properties
3) fibrinolytic properties
How does uninjured endothelium prevent platelet adherence?
via prostacyclin, NO, and ADP phosphatase (all are platelet inhibitors or platelet aggregation and produced by endothelial cells)
What factors mediate endothelium anticoagulant properties?
1)heparin-like molecules
2) thrombomodulin
How do heparin-like molecules work to mediate endothelial anticoagulation?
they allow antithrombin III to inactivate:
1) thrombin
2) factor 10a
How does thrombomodulin work to mediate endothelial anticoagulation?
Binds thrombin and converts it to an anti-coagulant that activates protein C (an anticoagulant)
What is the function of protein C?
How does protein C work?
inhibits clotting by proteolytically cleaving factors 5a and 8a
What is protein S?
A co-factor for protein C
What factors mediate the fibrinolytic properties of endothelial cells?
tissue-plaminogen factor
How does t-PA work?
It clears fibrin deposits from endothelial surfaces.
What is the function of vFW?
Facilitates the adhesion of platelets to subendothelial collagen.
Is vFW specifically synthesized after endothelial injury?
No, it is a product of normal endothelium and is found in the plasma.
Where is vFW found?
On the surface of endothelial cells.
What is the stimulus for secretion of tissue factor?
TNF, IL-1, or bacterail endotoxin
What factor activates the extrinsic clotting pathway?
"tissue factor"
What is the function of "plasminogen activator"?
Depresses fibrinolysis
Is vFW only produced after injury?
No, it is constitutively produced
What cells produce vFW?
endothelial cells
Does tissue factor activate the extrinsic or intrinsic pathway?
What are the 2 types of granules that platelets contain?
1) α-granules
2) δ-granules
What type of adhesion molecule do α-granules display on their membranes?
What do α-granules contain?
1) fibrinogen
2) fibronectin
3) factor 5
4) factor 8
5) platelet factor 4
7) TGF-α
What do δ-granules contain?
2) ionized calcium
3) histamine
4) serotonin
5) epinephrine
What is the most important componen of ECM that platelets encounter after vascular injury?
What are the 3 general reactions that platelets undergo upon contact with ECM after vascular injury?
1) adhesion & shape change
2) secretion ("release reaction")
3) aggregation
What is the name for the deficiency in vFW?
von Willebrand disease
What is the receptor that platelets use to bind vFW?
glycoprotein Ib (GpIb)
What is the name of the disease for deficiency in GpIB?
Bernard-Soulier syndrome
What are 2 important mediators of platelet aggregation?
1) ADP
2) Thromboxane A2
What do ADP and thromboxane A2 do?
Mediate formation of primary hemostatic plug via autocatalytic reaction
Is the primary hemostatic plug reversible or irreversible?
What additional factor binds to the primary hemostatic plug to turn it into a secondary hemostatic plug?
Is the secondary hemostatic plug reversible or irreversible?
What does thrombin convert?
Fibrinogen to fibrin
What does fibrin do?
Cements the secondary hemostatic plub in place
What is the function of GPIIb-IIIa?
binds fibrinogen
What is the name for deficiency in GPIIb-IIIa?
Glanzmann thrombasthenia
Where is GpIIb-IIIa found?
On the surface of platelets.
What is the function of fibrinogen?
connects multiple platelets together to form aggregates
What platelet receptor does fibrinogen bind to?
What is the function of Thromboxane A2?
It is a platelet derived prostaglandin that promotes platelet aggregation
Where is Thromboxane A2 synthesized?
What is the function of PGI2?
1) vasodilator
2) inhibitor of platelet aggregation
What does antithrombin bind to to inhibit thrombosis?
heparin like molecule located on endothelial cells
What does thrombin bind to to inhibit thrombosis?
thrombomodulin located on endothelial cells
What does binding of antithrombin to heparin-like molecules cause?
inactivation of:
1) thrombin
2) factors 10a
3) factors 9a
What is the effect of thrombin binding to thrombomodulin?
causes endothelium toproduction of protein C which leads to proteolysis of factor5 and factor 9

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