Cardio Pathology Flashcards
1
Q
Factor V Leiden
A
- more common in Caucasian
- alters an amino acid residue in factor V and renders it resistant to protein C (failure of protein C to prolong aPTT)
- heterozygotes carry 5-fold increased risk for venous thrombosis, with homozygotes having a 50-fold increased risk
- seen to exist in compound states with other defects (i.e. protein C, protein S, or ATIII deficiency)
- 35 fold incrtease of developing DVT if taking OCPs
2
Q
Prothrombin mutation (G20210A variant)
A
- single-nucleotide substitution
- results in more stable mRNA and increased prothrombin transcription
- three-fold increased risk for venous thromboses
- heterozygotes at increased risk of VTE
- compound heterozygous state in conjunction with other thrombophilias seen
- young age of first thrombosis
- up to 40% of homozygotes may not experience thrombotic event
3
Q
Hyperhomocysteinemia
A
- vitamin B12 deficienc
- folate deficiency
- lack of vitamin B12 or folate leads to decreased conversion of homocysteine to methionine resulting in buildup of homocysteine
- cystathionine beta synthase (CBS) deficiency results in high homocystein elevels with homocystinuria
- CBS converts homocysteine to cystathionine; enzyme build up leads to homocysteine buildup
- characterized by vessel thrombosis mental retardation, lens dislocation, and long slender fingers
4
Q
Heparin-Induced Thrombocytopenic (HIT) syndrome
A
- occurs in up to 5% of patients treated with unfractionated heparin
- development of auto-antibodies that bind complexes of heparin and platelet membrane protein (PF-4)
- antibodies may bind similar complzes present on platelet and endothelial surfaces, resulting in platelet activation, aggregation, and consumption (thrombocytopenia)
- causes prothrombotic state
- fragments of destroyed platelets may activate remaining platelets, leading to thrombosis
5
Q
Antiphospholipid Antibody Syndrome
A
- recurrent thrombosis, repeated miscarriages, cardiac valve vegetations, thrombocytopenia
- associated with autoantibodies directed against anionic phospholipids (e.g. cardiolipin) or , more accurately, plasma protein antigens that are unveiled by binding to such phospholipids (e.g. prothrombin)
- induces hypercoagulable state, perhaps by inducing endothelial injury, by activating platelets or complement directly, or by interacting with the catalytic domains of certain coagulation factors
- secondary antiphospholipid syndrome –> well defined autoimmune disease such as lupus
- primary antiphospholipid syndrome –> hypercoagulable state without evidence of another autoimmune disorder
6
Q
Protein C/Protein S Deficiency
A
- decreases negative feedback on the coagulation cascade
- normally inactivate factors V and VIII
- increased risk of warfarin skin necrosis
- in preexisting C or S deficiency, a severe deficiency is seen at the onset of warfarin therapy increasing risk for thrombosis, especially in the skin
7
Q
Antithrombin III Deficiency
A
- decreases the protective effect of heparin-like molecules produced by the endothelium
- increases risk of thrombus
- heparin-like molecules normally activate ATIII, which inactivates thrombin and coagulation factors
- in ATIII deficiency, PTT does not rise with standard heparin dosing because heparin levels cannot activate limited ATIII
- high doses of heparin activate limited ATIII; coumadin is then given to maintain an anticoagulated state
8
Q
Thrombotic Thrombocytopenic Purpura (TTP)
A
- pathologic formation of platelet microthrombi in small vessels
- platelets are consumed in the formation of microthrombi
- RBCs are sheared as they cross microthrombi, resulting in hemolytic anemia with schistocytes
- due to decreased ADAMTS12, an enzyme that normally cleaves vWF multimers into smaller monomers for eventual degradation
- large uncleaved multimers lead to abnormal platelet adhesion, resulting in microthrombi
9
Q
Warfarin Induced Skin Necrosis
A
- microvascular thrombosis
- may occur in patients with heterozygous protein C or S deficiency if a high initial dose is used or heparin overlap is inadequate
10
Q
Bernard-Soulier syndrome
A
- due to a genetic GPIb deficiency
- platelet adhesion is impaired
- blood smear shows mild thrombocytopenia with enlarged platelets
11
Q
Glanzmann Thrombasthenia
A
- genetic GPIIb/IIa deficiency
- platelet aggregation impaired
12
Q
Aspirin
A
- irreversibly inactivates cyclooxygenase
- lack of TXA2 impairs aggregation
13
Q
Uremia
A
- disrupts platelet function
- both adhesion and aggregation are impaired
14
Q
Hemophilia A
A
- genetic factor VIII deficiency
- X-linked recessive
- deep tissue, joint, and postsurgical bleeding
- increased PTT; normal PT
- normal platelet count and bleeding time
- treatment: recombinant FVIII
15
Q
Hemophilia B
A
- genetic factor IX deficiency
- resembles hemophilia A
16
Q
Von Willebrand Disease
A
- genetic vWF deficiency
- most common inherited coagulation disorder
- mild mucosal and skin bleeding
- increased bleeding time
- increased PTT; normal PT (decreased VIII half-life)
- abnormal ristocetin test
17
Q
Ristocetin
A
- induces platelet agglutination by causing vWF to bind platelet GPIb
- lack of vWF –> impaired agglutination –> abnormal test
18
Q
Vitamin K Deficiency
A
- vit. K is activated by epoxide reductase in the liver
- activated vit. K gamma carboxylates factors II, VII, IX, X, and Proteins C and S
- deficiency in newborns (lack of GI colonization)
- deficiency in long-term antibiotic use
- malabsorption causes deficiency
19
Q
Disseminated Intravascular Coagulation (DIC)
A
- pathologic activation of the coagulation cascade
- widespread microthrombi result in ischemia and infarction
- consumption of platelets and factors results in bleeding
- secondary to OB complications, sepsis (endotoxins), adenocarcinoma, acute promyelocytic leukemia, rattlesnake bite
- decreased platelet count
- increased PT/PTT
- decreased fibrinogen
- elevated D-dimer
20
Q
Temporal (Giant Cell) Arteritis
A
- large-vessel vasculitis
- granulomatous vasculitis of branches of carotid artery
- headache (temporal artery), visual disturb. (ophthalmic artery, jaw claudication
- flu sxs and joint pain (polymyalgia rheumatica) - ESR elev.
- inflammed vessel wall with giant cells and intimal fibrosis
- treatment: corticosteroids
- high risk of blindness without treatment
21
Q
Takayasu Arteritis
A
- large-vessel vasculitis
- granulomatous vasculitis of aortic arch at branch pts
- adults )
- ESR elevated
- treatment: corticosteroids
22
Q
Polyarteritis Nodosa
A
- medium vessel vasculitis
- necrotizing vasculitis involving multiple organs
- lungs are spared
- HTN in young adults (renal artery involvement)
- abd pain with melena (mesenteric artery)
- neurologic disturbances and skin lesions
- serum HBsAg
- early lesions: transmural inflamm. with fibrinoid necrosis
- late lesions: heal with fibrosis, producing “string of pearls” appearance on imaging
- treatment: corticosteroids and cyclophosphamide
- fatal if not treated
23
Q
Kawasaki Disease
A
- medium vessel vasculitis
- Asian children < 4 years old
- nonspecific sxs: fever, conjunctivitis, erythematous rash of palms and soles, enlarged cervical lymph nodes
- coronary artery involvement is common
- thrombosis with MI
- aneurysm with rupture
- treatment: aspirin and IVIG
24
Q
Buerger Disease
A
- medium vessel vasculitis
- necrotizing vasculitis involving digits
- ulceration, gangrene, autoamputation of fingers/toes
- Raynaud phenomenon often present
- highly associated with heavy smoking
- treatment: smoking cessation
25
Q
Wegener Granulomatosis
A
- small vessel vasculitis
- necrotizing granulomatous vasculitis involving nasopharynx, lungs, kidneys
- middle-aged male with sinusitis or nasopharyngeal ulceration, hemoptysis with bilateral nodular lung infiltrates, and hematuria (rapidly dev. glomerulonephritis)
- treatment: cyclophosphamide and steroids
26
Q
Microscopic Polyangiitis
A
- small vessel vasculitis
- necrotizing vasculitis involving multiple organs
- commonly the lungs and kidneys
- similar to Wegener, but nasopharyngeal involvement and granulomas are absent
- treatment: corticosteroids and cyclophosphamide
27
Q
Churg-Strauss Syndrome
A
- small vessel vasculitis
- necrotizing granulomatous inflammation with eosinophils involving mult. organs, (lungs and heart esp.)
- asthma and peripheral eosinophilia are often present
28
Q
Henoch-Schonlein Purpura
A
- small vessel vasculitis
- due to IgA immune complex deposition
- most common vasculitis in children
- palpable purpura on buttocks and legs
- GI pain and bleeding
- hematuria (IgA nephropahty)
- usually occurs following URI
- treatment: steroids, if severe
29
Q
Atherosclerosis
A
- intimal plaque that obstructs blood flow
- necrotic lipid core with fibromusc. cap
- often undergoes dystrophic calcification
- large and medium sized arteries
- damaged endothelium - lipids leak into intima
- lipids consumed by macrophages - foam cells
- inflammation and healing - deposition of ECM and proliferation of smooth muscle
- begins as fatty streaks (arise early in life)
- peripheral vascular disease (e.g. popliteal)
- angina (coronary arteries)
- ischemic bowel disease (mesenteric arteries)
- MI and stroke due to plaque rupture
- aneurysm due to weakening vessel wall (e.g. abd aorta)
30
Q
Hyaline Arteriolosclerosis
A
- narrowing of small arterioles
- hyaline: proteins leaking into the vessel wall causing vascular thickening; proteins seen as pink hyaline
- consequence of long-standing benign HTN or diabetes
- reduced vessel caliber with end-organ ischemia
- glomerular scarring that slowly progresses to chronic renal failure
31
Q
Hyperplastic Arteriolosclerosis
A
- narrowing of small arterioles
- thickening of vessel wall by hyperplasia of smooth muscle (“onion-skin” appearance)
- consequence of malignant hypertension
- reduced vessel caliber with end-organ ischemia
- fibrinoid necrosis of the vessel wall with hemorrhage
- acute renal failure with characteristic “flea-bitten” appearance
32
Q
Monckeberg Medial Calcific Sclerosis
A
- calcification of the media of muscular (medium-sized) arteries
- non-obstructive
- not clinically significant; seen as incidental finding on CXR or mammography
