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245 Cards in this Set
- Front
- Back
What are the late manifestations of Lymphedema?
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1)peau d'orange-thickened skin due to advanced lymphedema of all causes
2) can get a secondary infection in longstanding lymphedema 3)lymph vessel cancer (lymphangiosarcoma) |
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What is dependent edema?
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it is very common, due to impaired venous return
-may occur without significant pathology, long periods standing, confining air/car travel -pregnancy, hormones (PMS), RV heart failure -involves lower extremities of ambulatory pts., but if pt. bedridden edema is over sacrum -see pitting edema -dependent means that the fluid goes wherever gravity is pulling |
|
Describe generalized subcutaneous edema.
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-affects all parts of the body equally, fluid accumulation in loose tissues
-periorbital edema is a sign -anasarca: severe generalized edema -can be due to nephrotic syndrome, endstage liver disease due to severe hypoproteinemia, severe CHF in which edema is related to hydrostatic pressure, shock-increased permeability |
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What is anasarca?
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severe generalized edema
|
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What causes pulmonary edema?
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Left ventricular failure is number one cause
-the lungs will increase in wt. 2-3X, frothy blood-tinged fluid, hemosiderin laden macrophages in alveoli (stain with Prussian blue) |
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What can cause generalized cerebral edema and what will the brain look like?
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hypertensive crisis
-brain swollen with flattened gyri, narrowed sulci, will see papilledema of retina |
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What is an effusion?
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edema in serous cavities
|
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What does a serous effusion look like grossly?
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appears as a yellow colored transparent fluid
|
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What causes chylous effusions?
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leakage of chyle from the lymphatic channels or thoracic duct
-caused by traumatic disruption of thoracic duct obstruction by a tumor for example (most of these ppl. have a mediastinal tumor) -appears milky and is high in triglycerides, chylomicrons present |
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What is hyperemia?
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same thing as erythema
-it is active, arteriole dilation and the red color due to increased oxygenated blood -caused by exercise, inflammation (cytokines, TNF, etc. act on endothelium to produce vasodilation) |
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What is congestion?
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a passive process (unlike hyperemia)
-impaired venous outflow from tissues/stasis -caused by heart failure:damming of blood return -also caused by local venous obstruction -tissues are blue red (cyanosis)-hypoxic -commonly associated with edema (transudate due to increased HS pressure) -leads to a chronic passive mechanism of injury in which the blood vessels are dilated, circulation is impeded, there is hypoxic injury which leads to cells death, see microscopic scarring, capillary rupture produces focal hemorrhages; siderophages accumulate |
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What is the cause of hepatic congestion and what is the morphology of the liver?
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caused by R. sided heart failure
-nutmeg liver with red brown depressed areas due to centrilobular hemorrhagic necrosis -AST, ALT, LH elevated due to necrosis of hypoxic hepatocytes (in zone 3 mostly) -in persistent/chronic congestion, siderophages accumulate and chronic disease leads to fibrosis of liver |
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What causes congestive splenomegaly?
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with passive congestion of the spleen it is enlarged and soft
-caused by R. heart failure, hepatic cirrhosis, and portal vein occlusion/thrombosis (blood flow backs up to spleen) |
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What is brown induration of the legs?
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chronic venous insufficiency due to valve defects
-brown coloration due to accumulation of hemosiderin laden macrophages in dermis |
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What is a common complication of brown induration of the legs?
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stasis ulceration
|
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What is hemostasis?
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process by which plug of blood forms to rapidly close vessel injuries and the process that maintains blood within the vascular system fluid and free of clots
|
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What do "lines of Zahn" refer to?
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the often layered/laminated appearance of a thrombus
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What is a hemorrhage?
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-extravasation of blood from vessels
-results from vascular injury that leads to vessel rupture -may be internal into a tissue as well -external hemorrhage occurs into GI and GU tracts, and through defects (cuts, tears) in skin |
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What is a hematoma?
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a mass of blood confined within an organ, tissue, or internal space
|
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What is a contusion?
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causes bruise/ecchymosis
-blunt force injury damages small blood vessels w/o disruption of continuity of tissue |
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What is ecchymosis?
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a type of internal hemorrhage that is a large area >1-2 cm of bruising (bleeding into tissue)
-changes over time from red/blue to blue/green (heme converted to bilirubin) to gold brown (hemosiderin siderophages accumulate at site) |
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What are petechiae?
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also called punctate hemorrhages in the GI tract
-associated with thrombocytopenia (low # platelets) or dysfunctional platelets and suffocation |
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What are purpura?
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confluent petechiae >3 mm
-caused by vascular inflammation, trauma and anything else that causes internal hemorrhages |
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What is hemarthrosis?
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bleeding into joints
|
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What is a laceration?
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A tear due to blunt force trauma
-may be stellate (jagged) or linear -bridging strands of fibrous tissue or blood vessels |
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What is an incision?
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it is produced by sharp cutting object
-clean margins, no bridging |
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What is an abrasion?
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a scrape, superficial dermis torn off by friction or force
-usually heals w/o scar |
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What is hemoptysis?
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coughing up blood
|
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What is menorrhagia?
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excessive menstrual bleeding
(can be btwn. periods as well) |
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What are the prothrombotic effects of the endothelium?
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platelets: source of Von Willebrand factor
Procoagulant effect of endothelium: synthesis of tissue factor, augmentation of IXa, Xa -secrete PAI (plasminogen activator inhibitor) |
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What forms the molecular bridges in platelet adhesion?
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the bridges are formed between glycoproteins and collagen
-glycoprotein 1b (Gp1b) and von willebrand factor -this has a clinical implication in deficiencies of these factors will have defects in platelet adhesion -von willebrand disease and Bernard-Soulier syndrome (Gp1b defic.) |
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What causes the shape change in platelets during adhesion?
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binding ADP to its receptor
-the neg. charged phospholipid is expressed, degranulation occurs and ADP and Ca are released -the phospholipids and Ca complex with each other to form critical sites for assembly of coag. factors |
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What are the platelet aggregation mediators?
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ADP
TXA2 thrombin via receptor on platelets GpIIbIIIa-fibrinogen bridge-->aggregation -platelets contract and fibrinogen is converted to fibrin -aggregation then becomes irreversible -->secondary plug |
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What is Glansmann thrombasthenia?
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a hereditary defect of GpIIbIIIa
-this is a defect in platelet function via aggregation -the drug abiciximab also inhibits this GpIIbIIIa complex |
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What are some "antiplatelet" drugs used to affect platelet function, not number?
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1)ADP receptor PY2 inhibitors
2)GpIIbIIIa inhibitors (abiciximab) 3)aspirin, NSAIDS-block COX action on arachidonic acid, prevent production of TXA2 |
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What is thrombocytopenia?
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decreased # of platelets
-decreased production in bone marrow, increased peripheral destruction (autoimmune, HIV, etc) -dysfunctional platelets (uremia/kidney failure, DRUGS) |
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What is typically used as the surface for assembly of the coagulation cascade?
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a phospholipid surface
-formed by platelet plug and endothelium -the reaction is then held together by Ca ions |
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Where are plasma coag. factors manufactured?
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in the liver
|
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Which clotting factors are vitamin K dependent? Which anticoagulants are vit. K dependent?
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VII, IX, X, II
natural anticoagulants: proteins C, S -post-translational modification of these proteins supplies the gamma carboxyl groups required for Ca binding |
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What 2 enzymes act upon fibrinogen and what are their effects?
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1)thrombin-cleaves fibrinogen to fibrin releasing monomers which polymerize and form an insoluble gel
2)plasmin-cuts fibrin into peptides (called fibrinolysis) and forms fibrin degradation products and d-dimer (cross linked fibrin product used as a lab test for thrombosis) |
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What factor cross links fibrin to further stabilize it?
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activated factor XIIIa
|
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What is the function of thrombin?
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it is a potent enzyme which is activated from prothrombin via the prothrombinase complex (factors V and X)
-amplifies formation of additional thrombin -stabilizes clot via activation of factor XIII -converts fibrinogen to fibrin-forms clot -inhibits thrombin formation via feedback -can be proinflammatory and anti-inflammatory (via receptors) -affects repair/healing (activates endothelium, monocytes, PMNs, lymphocytes and promotes platelet aggregation) |
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What are the sources of tissue factor?
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walls of blood vessels, endothelial cells, monocytes, cells in CT
-can be induced by cytokines -endothelial cells release tissue factor pathway inhibitor |
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What is another name for factor XII?
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Hagemann factor
-it is a contact factor in the intrinsic pathway and its role in vivo is not understood -deficiency causes neither bleeding or thrombosis |
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What does the aPPT test evaluate?
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the instrinsic clotting pathway
|
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What does the PT test evaluate?
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the extrinsic clotting pathway
|
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Describe what the findings of an abnormal PT test would suggest and what clinical feature it is used to monitor?
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add tissue factor, Ca, and phospholipids to a tube along with pts blood
-the clot time will be prolonged in extrinsic factor and common pathway factor deficiencies VII, X, V, II, I -this test is used to monitor coumadin therapy |
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What would an abnormal aPTT test result indicate and what clinical treatment does it monitor?
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time to clot formation usually less than 40 seconds
-prolonged in deficiencies of XII, XI, X, V IX, VIII, II, I (intrinsic and common pthways) -monitors unfractionated heparin therapy |
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What are some causes of acquired defects of secondary hemostasis?
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liver disease (severe), vit. K defic, anticoagulant drugs, DIC
|
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What are the most common hereditary deficiencies of clotting factors?
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factor VIII and VW factor
|
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What is the inheritance pattern of factors VIII and IX deficiencies?
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X-linked
|
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How is Von willebrand disease inherited?
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autosomal dominant and rarely, it is recessive
|
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How are most clotting factor deficiencies inherited?
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most are autosomal recessive except for the ones that we know are inherited otherwise
|
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How does coumadin/warfarin work?
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it is a vit. K antagonist
-common therapeutic agent for persons prone to thrombosis, may cause excessive bleeding |
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What are some causes of Vit. K deficiency?
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malabsorption-pancreatic insufficiency including cystic fibrosis, bile duct obstruction (b/c vit K is fat soluble), intestinal disease involving ileum
-antibiotic therapy -dietary deficiency -coumadin therapy -it is deficient in many neonates, shot given at birth |
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What labs would be abnormal in the case of a vit. K deficiency?
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the PT would be prolonged early/first
-PTT prolonged in severe deficiency |
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What laboratory test would be abnormal in a pt. with Hemophilia A or B?
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PTT
A=factor VIII B=factor IX |
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What is tissue plasminogen activator and where is it produced?
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it is a natural antithrombotic product of endothelial cells
-it acts as a "clot buster" -activates plasminogen-->plasmin, which then lyses fibrin/fibrinogen -recombinant tPA is used in MI, stroke in first 3 hrs, pulmonary embolism |
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What are the 3 natural anticoagulants?
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antithrombin III
Protein S Protein C -deficiencies in these are associated with abnormal tendency to clot (thrombophillia) |
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What is the function of Antithrombin III?
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activated by binding to heparin like molecules on endothelial cells or by therapeutic heparin injections
-the ATIII/heparin complex inhibits thrombin and other serine proteases IXa, Xa, XIa |
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What is the most severe form of thrombophilia?
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hereditary ATIII defic. but luckily it is very rare
|
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What is the function of Protein S?
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vit. K dependent cofactor of protein C
-made in endothelial cells, liver, etc. -natural anticoagulant |
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What is the function of protein C?
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vit. k dependent natural anticoagulant
-made in the liver -activated by binding of thrombin to endothelial thrombomodulin |
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What do the activated protein C/S complex inactivate?
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Va, VIIIa
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What are the major activators of the fibrinolytic cascade?
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factor XIIa dependent pathway
-tPA -urokinase-like plasminogen activator -streptokinase, bacterial product |
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What is the function of PAI (plasminogen activator inhibitor)?
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blocks the action of tPA
-made by endothelial cells; fat cells (increased in obesity) -alpha2 plasmin inhibitor neutralizes free plasmin |
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What is thrombosis?
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pathologic process formation of a clot within intact vascular system
-pathogenesis: Virchow's triad 1)endothelial injury 2)stasis or turbulence of blood 3)blood hypercoagulability |
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What is Virchow's triad?
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endothelial injury
stasis or turbulence of blood blood hypercoagulability -these all lead to THROMBOSIS! |
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What is a Leiden mutation? How can we test for it?
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hereditary thrombophilia, primary mutation of Factor V
-up to 60% of pts. with recurrent DVT -single AA sub. results in factor Va that is resistane to digestion by activated protein C -Lab tests: activated Protein C resistance, genetic testing for mutation available too |
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What is prothrombin 20210A?
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-a type of hereditary thrombophilia
-the mutation resulst in increased levels of prothrombin -increased prothrombin drives more fibrinogen-->fibrin |
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What is hyperhomocysteinemia?
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mutation in methyltetrahydrofolate reductase
-inhibits antithrombin III activity and thrombomodulin -contributes to formation of atherosclerosis -the acquired form would be a B12 or folate deficiency |
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When would one consider a diagnosis of inherited thrombophilias?
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thrombosis under age 50 esp. in childhood, recurrent thrombosis, unusual sites of thrombosis (ex. hands), thrombosis in pregnancy or postpartum, thrombosis with no acquired predisposition
|
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Describe heparin-induced thrombocytopenia.
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-abs form to heparin complexed with heparin platelet factor 4
-binding activates platelets: formation of platelet rich thrombi -thrombocytopenia due to platelets consumption |
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What is antiphospholipid syndrome?
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-primary solitary AI defect, or secondary to SLE
-abs may occur in clinically normal pts. -risk for recurrent venous or arterial thrombi (stroke, MI, DVT with pulmonary emboli) -clinical findings include repeated miscarriages, caridac valvular vegetations called Libman-Sachs, thrombocytopenia |
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What is the most common significant location of DVTs?
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deep veins of legs are source of 90% of cases of pulmonary embolism
|
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Describe superficial saphenous thrombophlebitis.
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associated with varicosities
-the varicosities result in stasis, thrombosis -thrombi produce local congestion, pain, swelling -these RARELY EMBOLIZE -predispose to venous insufficiency; varicose ulcers of skin |
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Describe the clinical signs and diagnosis of DVT.
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asymptomatic in half
-usually found as a consequence of pulmonary emboli -may result in edema, swelling of leg -normal D-dimer excludes most DVT -can do u/s imaging of vein |
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What is the most common cause of arterial thrombosis?
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atherosclerosis (caused by turbulence and endothelial injury)
-mural thrombus within the chamber of a heart is the most important source leading to systemic emboli -aneurysms along with other sources also contribute |
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What is cor pulmonale?
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hypertrophy of right ventricle due to lung disease; leads to R. heart failure
|
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What is a saddle embolus?
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occludes both L and R pulmonary arteries at the bifurcation, person will die w/in seconds
-produces electrical mechanical dissociation (EKG activity with no pulse) |
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What is the most common source of pulmonary emboli?
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Deep veins of the leg above level of popliteal fossa
-can also come from R. ventrical mural thrombus (cannot come from L. ventricle or Int. carotid arteries) |
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What is the most common site of arterial embolization?
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lower extremities (75%)
-brain 10% retina, intestines, kidneys, spleen |
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What is traumatic fat embolism?
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-occurs with trauma, usually fracture of long bones (with marrow)
-fat embolism syndrome occurs in a minority of pts. with embolization (shortness of breath followed by confusion, coma, 1-3 days after fracture, can be fatal) |
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What is air embolism?
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-form of barotrauma
-bubbles of air or gas w/in circulation -can be caused by OB procedures, tx of pneumothorax, lung/chest wall injury -clinically significant >100cc air -endogenous air embolism (decompression sickness) caused in scuba/deep sea divers, air at high pressure dissolves in blood and tissues (eg nitrogen), during rapid ascent bubbles form in the blood, gas emboli form and occlude arteries leading to ischemia -pts. present with the bends:pain in mm. and joints and the chokes (resp. distress), -tx immediately in decompression chamber |
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What is an amniotic fluid embolism?
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-infrequent complication of delivery
-occurs during delivery/immediately postpartum -there is an infusion of amniotic fluid into maternal circulation via tear -there will be fetal squames, hair, vernix fat, and meconium in pulmonary vessels -mother will have SOB, shock, followed by seizures, coma, DIC, fatal in up to 80% |
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What is an infarction?
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area of ischemic necrosis caused by occlusion of either the arterial supply or venous drainage of a tissue
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Where do hemorrhagic or red infarcts occur?
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-venous occlusions (twisted ovaries, testes)
-arterial occlusions in loose tissues (lungs), blood collects in infarcted zone -arterial occlusion in tissues with dual circulations (lungs, intestines) -occlusions in tissues previously congested -occlusions where the blood flow is re-established |
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What is a white infarct?
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occurs due to arterial occlusions in solid organs
-heart, spleen, kidney -density of tissue limits seepage from adjoining capillaries |
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Describe the morphology of infarcts.
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they are wedge-shaped, occluded vessel at apex
-fibrinous exudates on overlying serosa -at the microscopic level there will be the initial hemorrhage, coagulative necrosis, and then hemosiderin laden macrophages after 48 hrs. |
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What causes most cases of familial hypercholesterolemia?
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LDL receptor defects
|
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What is the current standard initial test for hyperlipoproteinemias?
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total cholesterol and TGs
LDL and HDL cholesterol -risk index (Framingham) can be calculated |
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What is the most common familial hyperlipidemia?
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familial hypercholesterolemia
autosomal dominant and common -genetic defects in LDL receptor result in inadequate hepatic uptake of LDL and serum levels are increased, LDL is oxidized and is toxic to endothelium, phagocyte eats cholesterol=foam cells -accumulate in vessel walls-atherosclerosis -accum. in skin/tendons-xanthomas |
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What would heterozygotes with familial hypercholesterolemia look like?
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-plasma cholesterol increased from birth 2-3 X
-may have cutaneous xanthomas -premature atherosclerosis develops in adults |
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What do homozygotes with familial hypercholesterolemia present with?
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-plasma cholesterol 5-6 X normal (>500 mg/dL)
-skin and tendinous xanthomas in childhood -coronary, cerebral, and peripheral vascular atherosclerosis in childhood, adolescence |
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What are the 3 steps involved in healing damaged intima?
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1)recruitment of sm. mm. cells or sm. mm. precursor cells to the intima
2)sm. mm. cell mitosis 3)elaboration of extracellular matrix |
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What are the 2 major hemodynamic variables regulating normal BP?
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1) CO
2) Total peripheral resistance -accounted for by resistance of arterioles, thickness of vessel wall, neural and hormonal influences that constrict or dilate -autoregulation-increased blood flow to vessel leads to vasoconstriction |
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What is essential HTN?
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AKA primary HTN
-idiopathic and most common, accounts for 90-95% of HTN |
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What is benign HTN?
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HTN at modest level and fairly stable over years
-95% of cases |
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What is malignant HTN?
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systolic >200, diastolic > 120
-rapidly rising BP, untreated leads to death w/in 2 years -may develop in previously noromotensive person, often superimposed on pre-existing benign |
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What are the 2 most common forms of ateriolosclerosis and what does each signify?
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1)hyaline-common in diabetics, major characteristic of benign nephrosclerosis, homogenous, pink hyaline thickening of the walls of arterioles with loss of underlying structural detail and narrowing of lumen
2)hyperplastic-related to acute, severe elevations in BP, characteristic of malignant -onionskin, concentric, laminated thickening of walls of arterioles with progressive narrowing of lumen -may see necrotizing arteriolitis (deposits of fibrinoid and acute necrosis of vessel wall) |
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What are the 3 types of arteriosclerosis?
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1)atherosclerosis (dominant pattern)-intimal fibrous plaques with lipid rich core
2)Monckeberg's medical calcific sclerosis-calcification of the media of muscular artery (no clinical significance, usually adult >50 yo) 3)arteriolosclerosis-hyaline or hyperplastic |
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What is the lesion that characterizes atherosclerosis?
|
an atheroma or fibrofatty plaque
-raised focal plaque w/in intima with a lipid core and covering fibrous plaque |
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What are the constitutional (non-modifiable) risk factors for ischemic heart disease?
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increasing age
male gender family history genetic abnormalities |
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What are the modifiable risk factors for ischemic heart disease?
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hyperlipidemia
HTN smoking diabetes C-reactive protein |
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What is an aneurysm?
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a localized abnormal dilation of vessel
-occurs most commonly in aorta or heart -can be true or false |
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What is a true aneurysm?
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bounded by complete arterial wall components
-blood remains within confines of circulatory system -ex: atherosclerotic, left ventricle after MI and congenital |
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What is a false aneurysm?
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extravascular hematoma that communicates with intravascular space
-leak at anastomosis of vascular graft with artery |
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What factors with respect to the CT in the vascular wall can lead to an aneurysm?
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1)the vascular wall CT is inherently weak
-ex: Marfan syndrom-defective synthesis of fibrillin leads to abnormal TGF-beta and progressive weakening of elastic tissue, aorta progressive dilation and remodeling of inelastic media -ex: Loeys-Dietz syndrome-mutations in TGF-beta receptors-abnormalities of elastin, collagen I and III -ex: Ehlers-danlos-defective collagen type III synthesis -ex: vit. C deficiency-altered collagen cross-linking 2)the balance of collagen degradation and synthesis altered by inflammation -increased MMP production by macrophages (atherosclerosis and vasculitis, enzymes degrade ECM) -decreased TIMP production 3)vascular wall weakened through loss of sm. mm. or inappropriate synthesis of noncollagenous or nonelastic ECM (cystic medial degeneration) |
|
What is cystic medial degeneration?
|
when ischemia leads to degenerative changes we call this cystic medial degeneration and it is non-specific
-there is scarring, inadequate ECM synthesis, increased amounts of amorphous ground substance -the vascular wall is weakened through loss of sm. mm. or inappropriate synthesis of noncollagenous or nonelastic ECM |
|
What are the 2 major disorders which predispose to aortic aneurysms?
|
1)atherosclerosis-AAA
2)HTN-ascending aorta |
|
What is a mycotic aneurysm?
|
infection of a major artery that weakens the wall
-originate from a septic embolus lodged in the vessel, extension of adjacent infection, circulating organisms directly infecting |
|
Where do aneurysms associated with atherosclerosis most commonly occur?
|
in the abdominal aorta
|
|
Who is more likely to get a AAA?
|
more frequent in men and smokers, rarely before age 50, other factors also contribute, only 5% of men >60 have AAA
|
|
Describe the morphology of an AAA.
|
-seen below the renal arteries and above bifurcation of aorta
-up to 15 cm in diameter, 25 cm in length -intimal surface=severe complicated atherosclerosis -there is destruction, thinning of underlying aortic media -filled with mural thrombus (either inflammatory or mycotic-infection by circulating organisms, particularly Salmonella gastroenteritis) |
|
What are the clinical sx of AAA?
|
-rupture into peritoneal cavity, retroperitoneal tissue=potentially fatal hemorrhage
-impingement on adjacent structure -occlusion of branch vessel=ischemia downstream -embolism from atheroma or mural thrombus -creation of abdominal mass-often palpably pulsating |
|
At or above what size are AAAs at greatest risk for rupture?
|
>5cm are managed surgically with bypass grafts
-over 50% mortality with a ruptured AAA |
|
What are the clinical sx associated with a thoracic aortic aneurysm?
|
-encroachment on mediastinal structures
-resp. difficulties, encroaches on lungs, airways -difficulty swallowing, compresses esophagus -persistent cough, pressure on recurrent laryngeal nerve -pain caused by erosion of bone -cardiac disease -rupture |
|
What disease is a Thoracic aortic aneurysm associated with?
|
-syphilis (luetic)
-usually confined to thoracic aorta and arch -ischemic damage to media due to inflammation within vasa vasorum of adventitia-obliterative endarteritis -scarring with contraction (tree barking) -may cause aortic valve ring dilation |
|
Define dissection.
|
dissection of blood along the laminar planes of the aortic media, with formation of a blood filled channel within aortic wall
-often ruptures with massive hemorrhage (may or may not be associated with dilation) |
|
What 2 groups of pts. do dissections occur in?
|
1)men 40-60 y.o., 90% have HTN
2)pts. with abnormality of CT that affects aorta (marfan syndrome) -note that this also rarely occurs in prego |
|
What is the major predisposing factor for dissections?
|
HTN
-medial weakness and inherited or acquired CT disorders can also contribute |
|
What is the most frequent detectable microscopic lesion?
|
cystic medial degeneration
-there is an initial intimal tear (transverse or oblique) |
|
What are the classical clinical sx for a dissection?
|
-sudden onset of excruciating pain, ant. chest, radiating to back, moving downward
-often confused with acute MI |
|
What is the most common cause of death with dissections?
|
rupture of dissection into any of 3 major body cavities (pericardial, pleural or peritoneal)
|
|
What are the 2 most common mechanisms for vasculitis?
|
1)infectious pathogens (direct invasion)
2)immune-mediated inflammation |
|
Why is it important to distinguish btwn the 2 mechanisms causing vasculitis?
|
for therapeutic reasons
-give immunosuppressive therapy for immune causes |
|
What are the common clinical findings in vasculitis?
|
-general term for vessel wall inflammation
-fever, myalgias, arthralgias, malaise, tissue ischemia |
|
What are the 3 main mechanisms which initiate noninfectious vasculitis?
|
1)immune complex deposition
2)antineutrophil cytoplasmic abs-pts serum reacts with cytoplasmic antigens in neutrophils 3)anti-endothelial cell abs |
|
What is an ANCA? What are the 2 types?
|
an anti-neutrophil cytoplasmic antibody
-many pts. have circulating ab's that react with neutrophil cytoplasmic agents -2 types based on immunofluorescence pattern 1)anti-myeloperoxidase (MPO-ANCA) -was the old p-ANCA 2)anti-proteinase 3 (PR3-ANCA), was the old c-anca |
|
In what 2 ways can ANCA's be useful clinically?
|
they are useful for diagnosis and following the activity of the disease
-perform ANCA titers |
|
Giant cell (temporal) arteritis affects what size vessels?
|
large vessels
|
|
What is the major morphologic finding in giant cell arteritis?
|
focal granulomatous inflammation of large to small size arteries
-affects primarily cranial vessels (temporal) -may see aortic involvement |
|
What age group is giant cell arteritis found in?
|
the elderly
|
|
What are the clinical sx of giant cell arteritis?
|
rare before age 50
-may have insidious presentation (fever, fatique, wt. loss) or sudden onset of headache, tenderness with swelling and redness and facial pain -ocular sx serious (ocular artery involved), occur in half of pts. |
|
How is giant cell arteritis treated?
|
with steroids
|
|
How is a diagnosis of giant cell arteritis made?
|
biopsy may be diagnostic but 1/3 are neg. due to segmental nature of lesion, need 2-3 cm length of vessel
-neg. biopsy doesn't r/o disease |
|
What disease is giant cell arteritis commonly associated with?
|
polymyalgia rheumatica
|
|
Takayasu arteritis affects what size vessel?
|
large
|
|
What is another name for Takayasu arteritis?
|
pulseless disease
|
|
What are the 2 main sx of Takayasu arteritis?
|
1)ocular disturbances
2)marked weakening of pulses in upper extremities |
|
What are the major morphologic findings in Takayasu arteritis?
|
-classically involves aortic arch, but 1/3 involve remainder of aorta and branches
-1/2 have pulmonary arteries involved -irregular thickening of vessel wall with intimal hyperplasia -aortic arch involvement=great vessels lumen decreased=pulseless disease -mononuclear inflammation, granulomatous inflammation, then collagenous fibrosis |
|
What is the course of Takayasu arteritis?
|
it is variable, rapid progression or quiescent stage after 1 or 2 years
|
|
PAN affects what size vessels?
|
medium
|
|
PAN (polyarteritis nodosa) affects renal and visceral vessels, what does it spare?
|
pulmonary
|
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What are the morphologic features of PAN?
|
-segmental transmural necrotizing inflammation
-has 3 stages (may coexist with each other) 1)acute-fibrinoid necrosis, neutrophils, eosinophils, mononuclear cells 2)healing-transmural scarring, continuing, continuing necrosis 3)healed-fibrotic thickening -weakened wall leads to aneurysm, clinically palpable nodule |
|
Do patients with PAN get glomerulonephritis?
|
NO b/c the small vessels are not affected
|
|
What age group does PAN affect?
|
typically a disease of young adults
|
|
What are the common manifestations of PAN?
|
can be acute, subacute or chronic with long remissions
-variable presentation -FUO, wt. loss, HTN, abdominal pain, melena, mm. aches and pains, peripheral neuritis |
|
What is the course of PAN w/o tx? With?
|
it is fatal if left untreated
-90% remission/cure tx with corticosteroids and cyclophosphamide |
|
What are the 3 features of Churg-Strauss syndrome?
|
1)granulomas
2)associated with asthma, allergic rhinitis 3)peripheral eosinophilia -same as PAN |
|
What ANCA is associated with Churg-Strauss?
|
MPO-ANCA in 50%
|
|
What is another name for Kawasaki disease?
|
mucocutaneous lymph node syndrome
|
|
What arteries does Kawasaki disease involve?
|
coronary
|
|
What are the sx of Kawasaki disease?
|
fever, conjunctival and oral erythema and erosion, edema of hands and feet, erythema of palms and soles and later desquamation, cervical lymphadenopathy
|
|
Pts. with Kawasaki disease usually develop what complications?
|
untreated 20% develop CV sequelae (MI, arteritis, aneurysms)
-treated with IV immunoglobulin and aspirin |
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What are the morphological features of Kawasaki disease?
|
transmural necrosis, inflammation like PAN but not as severe necrosis
|
|
What size vessels are affected in microscopic polyangitis?
|
small (arterioles, venules, capillaries)
|
|
How does microscopic polyangitis present?
|
palpable purpura involving skin or mucous membranes of lungs, brain, heart, GI, kidneys, mm.
-necrotizing glomerulonephritis and pumonary capillaritis are common (unlike PAN, this is the distinguishing feature) |
|
What are the major clinical features of microscopic polyangitis?
|
will see hemoptysis, hematuria, proteinuria, arthralgias, bowel pain, mm. pain/weakness, hemorrhage
|
|
How is a diagnosis of microscopic polyangitis made?
|
1)MPO ANCA (P-anca) in 70%
2)skin biopsy |
|
What are the morphologic features of microscopic polyangitis?
|
segmental fibrinoid necorisis or infilatration with neutrophils which fragment=leukocytoclasia
|
|
What is the triad that characterizes Wegener granulomatosis?
|
1)acute necrotizing granulomas of upper and/or lower resp. tracts
2)necrotizing or granulomatous vasculitis of small to med. size vessels mostly in lung and upper airway 3)renal disease-focal necrotizing often crescentic, glomerulonephritis |
|
What are the major morphologic features of Wegener's granulomatosis?
|
-URT lesions, inflammatory sinusitis due to mucosal granulomas
-ulcerative lesions of nose, pharynx or palate -necrotizing granulomas and necrotizing or granulomatous vasculitis -renal lesions-focal necrotizing or crescentic glomerulonephritis |
|
What are the clinical features of Wegener's granulomatosis?
|
-male>female, 40 yrs. average
-pneumonitis with b/l nodular and cavitary infiltrates, chronic sinusitis, ulceration of nasopharynx, evidence of renal disease |
|
What is the natural course of Wegener's granulomatosis?
|
if left untreated 80% die within one year
-treat with steroids, TNF antagonists, and cyclophosphamide -it is a chronic relapsing, remitting disease |
|
ANCA associated with Wegener's granulomatosis?
|
C-ANCA (PR3-ANCA)-95%
|
|
What is another name for Thromboangitis obliterans?
|
Buerger disease
|
|
What group of people get Buerger disease?
|
cig smokers.....YUCK!
|
|
What are the morphologic features of Buerger disease?
|
segmental, thrombosing, acute and chronic inflammation of intermed. and sm. arteries
-usually tibial and radial -acute and chronic inflammation with luminal thrombosis -microabscesses within thrombus, wall of granulomatous inflammation |
|
What are the clinical sx of Buerger disease?
|
present early with superficial nodular phlebitis
-cold sensitivity of hands, pain in instep induced by exercise -severe pain, even at rest -chronic ulcerations of toes, feet, or fingers may become gangrenous |
|
What is Raynaud phenomenon?
|
-Casey this one is a shout out to you!
-exaggerated vasoconstriction of digital arteries and arterioles -causes paroxysmal pallor or cyanosis of digits of hands or feet |
|
Who gets primary Raynaud phenomenon?
|
young females
usually benign, exaggeration of normal central and local vasomotor responses to cold or emotion |
|
What is secondary Raynaud phenomenon?
|
vascular insufficiency of extremities secondary to arterial narrowing from various processes
-ex. SLE, atherosclerosis, Buerger disease |
|
What are the sequelae of varicose veins?
|
persistent extremity edema
-trophic skin changes, stasis dermatitis, ulcerations, poorly healing wounds and infections may become chronic varicose ulcers, vulnerable to injury -embolism or other serious complications are rare |
|
What veins account for the majority of cases of thrombophlebitis and phlebothrombosis?
|
deep leg veins >90% of cases
-caused by inflammation and venous thrombosis |
|
What are the predisposing factors for thrombophlebitis and phlebothrombosis?
|
prolonged immobilization resulting in decreased blood flow through veins
-CHF, neoplasia, pregnancy, obesity -postop. state -systemic hypercoag. |
|
What are the local manifestations of thrombophlebitis?
|
edema distal to occluded vein
-dusky cyanosis -dilation of superficial veins -heat, tenderness, redness, swelling, pain -pain elicited by pressure over affected veins, squeesing calf mm. |
|
What is migratory thrombophlebitis and what's another name for it?
|
also called Trousseau sign
-associated with paraneoplastic syndrome in cancer pts. producing hyper coag. state -venous thrombosis in one site disappears and appears in another site |
|
What is a serious complication of DVT?
|
pulmonary embolism
|
|
Superior vena caval syndrome is caused by what?
|
obstruction of SVC, usually caused by neoplasms that compress or invade SVC
-mediastinal lymphoma, primary bronchogenic carcinoma, -clinical complex of dusky cyanosis, marked dilation of veins of head, neck and arms |
|
What is Inferior vena caval syndrome and what causes it?
|
obstruction of IVC
-neoplasms compress or penetrate walls of IVC or thrombus may propagate upwards -hepatocellular carcinoma and renal carcinoma have propensity to grow w/in lumens of veins with ultimate extension into IVC -will see marked leg edema, massive proteinuria b/c of involvement of kidneys, distension of superficial veins of lower abdomen |
|
What is the average size of the heart?
|
about 300 grams
|
|
What is a normal LV wall thickness?
|
1.5 cm
|
|
What is a normal RV wall thickness?
|
.5 cm
|
|
What are systolic dysfunctions of the heart?
|
ischemic injury, P/V overload, dilated cardiomyopathy
|
|
What are diastolic dysfunctions of the heart?
|
massive LV hypertrophy, myocardial fibrosis, deposition of amyloid, constrictive pericarditis
|
|
What 3 mechanisms does the CV system use to maintain pressure and perfusion in the face of damage or excess burden?
|
1)Frank-Starling-increase contractility
2)myocardial hypertrophy w/or without cardiac chamber dilation 3)activation of neurohumoral systems |
|
What 2 features characterize CHF?
|
1)diminished CO-forward failure
2)damming back of blood-backward failure |
|
What are the 3 most common underlying disease states for CHF?
|
1)diabetes
2)MI 3)HTN |
|
What are the 4 morphologic features seen in the heart in CHF?
|
-increased heart wt.
-progressive wall thinning -chamber dilation -microscopic changes of hypertrophy |
|
What are the 4 most common causes of L sided heart failure?
|
ischemic heart disease
HTN aortic and mitral valvular disease nonischemic myocardial diseases |
|
What happens to the atrium in L sided heart failure?
|
it enlarges and leads to A.fib
-may cause blood stasis with thrombus formation esp. in appendages -LEADS TO INCREASED RISK OF EMBOLIC STROKE! |
|
Pure R. sided heart failure occurs with what and what is this called?
|
with chronic severe pulmonary HTN and is called cor pulmonale
-there is RV pressure overload due to intrinsic disease of lungs or pulmonary vasculature |
|
What 4 changes occur in the liver during R sided heart failure?
|
1)nutmeg liver
2)centrilobular necrosis 3)central hemorrhagic necrosis (rupture of sinusoids) 4)cardiac sclerosis -long standing severe failure, central areas become fibrotic |
|
What 5 categories of heart disease account for almost all cardiac mortality?
|
1)ischemic heart disease (80-90%)
2)hypertensive heart disease and pulmonary HTN heart disease 3)certain valvular disease 4)congential heart disease 5)nonischemic (primary) heart disease |
|
In 90% or more of cases what is the underlying cause of myocardial ischemia?
|
coronary artery narrowing/obstruction due to atherosclerosis
|
|
What is another name for IHD?
|
coronary artery heart disease
|
|
What 4 syndromes describe the clinical manifestations of IHD?
|
angina
MI chronic ischemic heart disease sudden cardiac death |
|
What is acute plaque change?
|
disruption of previously, partially stenosing atherosclerotic plaque with
-hemorrhage, rupture and fissuring, erosion/ulceration -often followed by mural or total thrombus -severity depends on time course and amount of collateral circulation developing |
|
What are the acute coronary syndromes?
|
unstable angina, acute MI, sudden cardiac death
|
|
Describe stable angina. (typical)
|
due to reduction of coronary perfusion to a critical level by chronic stenosing atherosclerosis
-relieved by rest and Nitro |
|
Describe Prinzmetal variant angina.
|
pattern of episodic angina that occurs at rest
-due to coronary artery spasm -elevation of ST seg. on EKG -responds to Nitro and Ca channel blockers |
|
Describe unstable (cresecendo) angina.
|
pain occurs with progressively increasing frequency, ppt. with less effort, often occurs at rest, of prolonged duration
-induced by fissuring, ulceration or rupture of plaque with superimposed thrombus and possibly embolization -often precedes MI=preinfarction angina |
|
What are the 2 types of MI?
|
1)transmural (more common)-ischemic necrosis involves the full or nearly full thickness of ventricular wall in distribution of single coronary artery
2)subendocardial-ischemic necrosis limited to the inner 1/3 or at most 1/2 of the vent. wall, extends laterally beyond perfusion area of single artery |
|
What are the 5 proposed steps leading to an MI?
|
1)sudden change in morphology of plaque (hemorrhage, fissure, ulceration, etc)
2)platelet exposed to collagen and plaque, leads to platelet activation, aggreg, formation of platelet mass may give rise to emboli or occlusive thrombosis 3)tissue thromboplastin released, activates extrinsic pthway coag. 4)activated platelets release factors predisposing to coag. and favoring vasospasm 5)thrombus evolves to become completely occlusive |
|
What 7 things account for the location, size, and morphologic features of an MI?
|
1)location, severity and rate of development of coronary occlusion
2)size of vascular bed perfused by vessel 3)duration of occlusion 4)metabolic//O2 needs of at risk myocardium 5)extent of collaterals 6)presence site and severity of coronary arterial spasm 7)alterations in BP, heart rate and cardiac rhythm |
|
How does a transmural infarct differ from a subendocardial infarct?
|
transmural almost always involves a portion of LV, small % extend to RV,
-subendocardial infarct limited to inner 1/3 of myocardium |
|
What are the sequence of events grossly and microscopically for an MI?
|
-coag. necrosis and inflammation
-formation of granulation tissue -resorption of necrotic myocardium -organization of granulation tissue to form scar |
|
How may reperfusion to an infarct occur?
|
restore coronary blood flow by
-thrombolysis (dissolution by streptokinase or tissue type plasminogen activator) -balloon angioplasty-eliminates thrombotic occlusion and some of obstruction due to underlying plaque -coronary arterial bypass graft |
|
What 2 lab measurements are useful to diagnose an acute MI?
|
troponins-rise at 2-4 hrs, peak at 48 hrs, remain elevated for 4-7 days
CK-MB-rises within 2-4 hrs of MI, peaks at 24 hrs, return to normal at 72 hrs (overall looke for sx,EKG changes, and enzymes) |
|
What 4 factors are associated with a poor prognosis following an MI?
|
1)diabetes
2)female 3)advanced age 4) previous MI |
|
Which type of myocardial rupture is most common and when is it most likely to happen after an MI?
|
happens 3-7 days after MI
-usually free wall ruptures=death b/c leads to hemopericardium and tamponade |
|
What 3 things determine complications and prognosis after an MI?
|
infarct size, site, transmural extent
|
|
What is the age group usually affected by CIHD?
|
usually elderly, often prior MI, previous CABG
-usually have insidious development of CHF as a result of ischemic damage-postinfarction cardiac decompensation |
|
What is the morphology of the heart in CIHD?
|
usually enlarged and heavy due to LV hypertrophy and dilation
-scars of previous infarcts, coronary vessel disease |
|
What is the ultimate mechanism of death in sudden cardiac death?
|
lethal arrhythmia
|
|
What are the minimum criteria for diagnosing systemic hypertensive heart disease?
|
-LV hypertrophy (concentric) in absence of other causative pathology
-history or pathologic evidence of HTN |
|
What is the morphology of systemic hypertensive heart disease?
|
-LV pressure overload leads to LV circumferential hypertrophy w/o dilation
-symmetric wall thickening (>2 cm) -increased heart wt. (>500 gm) -stiff heart, impairs diastolic filling -decompensation occurs with dilation, thinning of wall, enlarged heart |
|
What are the clinical manifestations of systemic hypertensive heart disease?
|
compensated disease may be asymptomatic or can have onset of A. fib. from enlarged L atrium
-CHF with cardiac dilation |
|
What are the 2 types of cor pulmonale?
|
1)acute-RV dilation due to massive pulmonary embolism
2)chronic-RV hypertrophy and later dilation secondary to prolonged pressure overload from obstruction of pulmonary arteries or compression of septal capillaries -associated with chronic bronchitis, emphysema (COPD) |
|
What are the 4 disorders predisposing to cor pulmonale?
|
diseases of pulmonary parenchyma
diseases of pulmonary vessels disorders affecting chest movement disorders inducing pulmonary arterial constriction |
|
What are the 3 most common calcific valve diseases?
|
calcific aortic stenosis
calcific stenosis of congenitally bicuspid aortic valve mitral annular calcification |
|
What are the 2 types of calcific aortic stenosis?
|
1)age related (more common)
2)congenitally bicuspid -this is the most frequent valve abnormality |
|
What is the anatomic change in the heart associated with mitral valve prolapse?
|
-one or both leaflets are enlarged, redundant or floppy
-balloon or prolapse back into the L. atrium during systole -may be associated with Marfans, Ehlers danlos, may run in families -see myxomatous degeneration (attenuation of fibrosa layer of valve with deposition of mucoid material) |
|
What are the serious complications of MVP?
|
-infective endocarditis
-mitral insufficiency -stroke of systemic infarct from thrombi that form on valve -arrhythmias, sudden death uncommon |
|
What is the Jones criteria for diagnosing rheumatic fever?
|
evidence of strep. infection + presence of 2 major sx or 1 major and 2 minor sx
MAJOR:migratory polyarthritis of large joints, carditis, subcu. nodules, erythema marginatum of skin, sydenham's chorea (neurologic disorder) MINOR:fever, arthralgias, acute phase reactants |
|
What are the morphology features of acute rheumatic pancarditis?
|
Aschoff bodies in myocardium (collagen surrounded by lymphocytes and plump macrophages)
-fibrinous pericarditis in pericardium -fibrinoid necrosis with small vegatations in endocardium |
|
What are the characteristic lesions of infective endocarditis?
|
vegetations
|
|
What are the 2 types of infective endocarditis?
|
1)acute bacterial endocarditis-rapidly progressive over days, rapidly fatal
2)subacute bacterial endocarditis-clinical course of many weeks, months, fatal if not diagnosed and treated aggressively |
|
Describe acute bacterial endocarditis.
|
-heart valve usually normal prior to infection
-abrupt onset of fever, chills, -new murmur due to vegetations, valve destruction -early complications of bacteremia, embolization of vegetations (metastatic infections) -caused by virulent organisms: s aureus in IV drug users, |
|
Describe subacute bacterial endocarditis.
|
clinical course of weeks/months
-previously damaged valves present in half -due to low virulence organisms -ex. S. viridans group most common cause (oral source) -S epidermidis infects prostheses -S. bovis (GI tract infections) -slow onset, low grade fevers, wt. loss, malaise, murmur of underlying disease (ex. RF, MVP) -microemboli, petechiae common, immunologic lesions may occur, structural cardiac disease develops slowly |
|
What are the systemic complications of Infective endocarditis?
|
ischemic infarction, septic embolism with abscess, mycotic aneurysm, petechiae, subungual splinter hemorrhages, metastatic infection due to bacteremia, pneumonia, renal infarct, hematuria, cerebral and retinal emboli (roth spots), valve complications, myocardial abscess, splenomegaly, anemia of chronic disease, clubbing, splinter hemorrhages (Janeway lesions), circulating immune complexes cause glomerulonephritis and Osler's nodes,
|
|
What is a Roth spot associated with?
|
bacterial infective endocarditis
found in the eye, red with central white/cleared area |
|
Describe the cardiac morphology of infective endocarditis.
|
-vegetations on heart valves (bulky, friable or easily reduced to powder)
-localization of vegetations on valves, atrial side of AV valves, vent. surface of semilunar valves -mitral and aortic most commonly involved valves (source of systemic emboli) -tricuspid in 50% of IV drug use related IE: source of pulmonary emboli |
|
What are the cardiac complications of infective endocarditis?
|
-results in heart failure
-valvular disease-insuff./stenosis due to perforations, healing with fibrosis/calcifications -ring abscess:myocardium around valve destroyed, valve perforates and becomes insufficient -artificial valve dehiscence, suppurative pericarditis |
|
What is nonbacterial thrombotic endocarditis (NBTE)?
|
small, sterile thrombi deposits on valves
-associated with debilitation: cancer, sepsis -pathogenesis related to hypercoagulable states, pancreatic and other cancers (Trousseau syndrome) -fibrin deposits on valve leaflets w/o destruction -material may embolize |
|
What are the associations and consequences of Libman-Sacks endocarditis?
|
associated with AI of SLE and antiphospholipid syndrome
-mitral valve most commonly involved, vegetations are small, sterile, underside of valve affected -may fibrose and deform valve |
|
Describe the cardiac morphology and cause of carcinoid heart disease. What other substances are associated with similar morphology?
|
-caused by systemic serotonin, other agents produced and released by carcinoid tumors (lab test is 5-HIAA)
-the cardiac lesion is fibrous intimal thickening of RV, pulmonic/tricuspid valves -acid mucopolysacchardie matrix deposited, tricuspid insuff. most common, -similar lesion is seen on left due to serotonergic drugs: ergots, phen-fen and others |
|
What are the complications of artificial heart valves?
|
1)thromboembolic disease occurs with mechanical valves
2)infective endocarditis-uncommon but S. epidermidis is most likely cause 3)structural deterioration-major cause of failure, valve may tear, calcify, regurgitation 4)nonstructural dysfunction-hemolytic anemia, inadequate healing with paravalvular leak, exuberant healing with fibrosis |
|
Describe senile cardiac amyloidosis.
|
affects the elderly
-amyloid type of tranthyretin-some are Autosomal dominant mutations -african americans>caucasians |
|
What are 3 uncommon, distinctive causes of restrictive cardiomyopathy.
|
1)endomyocardial fibrosis-kids, young adults in africa
2)Loeffler endomyocarditis-associated with eosinophilia 3)endocardial fibroelastosis-childhood, congenital cardiac anomalies assoc, thickened endocardium: insignificant to fatal |
|
What is myocarditis?
|
inflammatory involvement of heart mm., characterized by a leukocyte infiltrate not secondary to ischemia; causes non ischemic degeneration of myocytes
-infections the most common cause, immune mediated rxns post infection or HS rxns, sarcoidosis, giant cell myocarditis |
|
What are the infectious causes of myocarditis?
|
Coxsackie A and B are the most common cause in US
-other enteroviruses -influenza -HIV -CMV Bacterial and fungal: Lyme disease, diphtheriae toxin mediated damage, trichinosis, toxoplasmosis, Chagas disease |
|
What are the cardiotoxic drugs?
|
cancer chemotherapies (doxirubicin, tyrosine kinase inhibitors, trastuzumab)
-lithium, chloroquine, phenothiazines -catecholamines, cocaine use |
|
What is the mechanism of injury to the heart due to catecholamines or cocaine use ?
|
direct toxicity to myocytes via Ca overload or vasoconstriction in face of tachycardia
-will see focal myocyte necrosis, contraction bands, sparse infiltrate of macrophages |