Midterm Flashcards
(575 cards)
1
Q
What kind of vessels does atherosclerosis affect
A
Mainly elastic and muscular arteries
2
Q
What kind of vessels does HTN affect
A
Mainly smaller muscular arteries and arterioles
3
Q
What is the intima made up of
A
Single layer of endothelial cells sitting on a BM; demarcated from media by internal elastic lamina
4
Q
What is the media like in each of the different vessels
A
- arteries: well organized concentric layers of smooth m cells, but veins are more haphazard
- media of elastic arteries has high elastin content (as we age, lose elastin and will raise systolic BP)
- muscular a: media composed of circumferential smooth m cells
5
Q
What are the principle points of physiological resistance to blood flow
A
Arterioles
6
Q
What is adventitia made up of
A
Loose connective tissue containing n fibers and vasa vasorum (small arterioles responsible for supplying outer portion of media of large arteries)
7
Q
What are the types of arteries
A
- elastic: aorta, Innominate, subclavian, common carotid, iliac, pulmonary
- medium sized or muscular arteries: coronary and renal aa
- small arteries and arterioles
8
Q
Do capillaries have a media
A
No *have slow flow rate nd huge cross sectional area
9
Q
Which tissues have the highest density of capillaries
A
Tissues with high metabolic rates (heart and brain)
10
Q
Where does most vascular leakage in inflammatory reactions occur
A
Post capillary venules
11
Q
What complications can AV fistulas cause
A
Rupture, shunting blood from arterial -> venous which forces heart to pump additional volume and can lead to high output cardiac failure
12
Q
What is FMD
A
-thickening of medial and intimate hyperplasia and fibrosis; can lead to aneurysms because adjacent segments have attenuated media
13
Q
What are the functions of endothelial cells
A
Have a nonthrombogenic surface to maintain blood in fluid state, modulate medial smooth m cell tone, metabolize hormones, regulate inflammation, and affect growth of other cell types
14
Q
What does vascular injury stimulate
A
Smooth m cell recruitment and proliferation resulting in intimate thickening
15
Q
What is the difference between neointimal smooth m cells that grow as a result of injury and medial smooth m cells
A
Neointimal: motile, undergo cell division and acquire new biosynthetic capability; noncontractile
16
Q
BPs above what are considered clinically significant for increased risk of atherosclerotic dz
A
> 139 systolic >89 diastolic; lower threshold when have other comborbidities
17
Q
What do most HTN patients die of
A
Ischemic heart dz, CHF or stroke
18
Q
What is the most important determinate of stroke volume
A
Filling pressure
19
Q
What is renovasular HTN
A
Renal a stenosis causes decreased glomerular flow and pressure in afferent arterioles of glomerulus
20
Q
What genetic disorders cause HTN
A
- gene defects affecting enzymes involved in aldosterone metabolism (aldosterone synthase, 11 beta hydroxylase, 17 alpha hydroxylase); primary hyperaldosteronism
- mutations of proteins that influence sodium reabsorption *liddle syndrome
21
Q
what is believed to be the initiating event for essential HTN
A
Reduced excretion of Na in normal BP
22
Q
what are the 2 forms of small vessel dz that HTN causes
A
Hyaline arteriolosclerosis and hyperplastic arterioloslerosis
23
Q
what is the morphology of hyperplastic arteriolosclerosis
A
Concentric laminated onion skin thickening of walls; in malignant HTN, accompanied by fibrinoid deposits and vessel wall necrosis (necrotizing arteriolitits)
24
Q
What are the 3 patterns of arteriosclerosis
A
- arteriolosclerosis affects small arteries and arterioles and can cause downstream ischemic injury; hyaline and hyperplastic are 2 types
- monckeberg medial sclerosis: calcification of walls of muscular aa; most commonly > 50 yo; calcification does not encroach on vessel lumen and usually not significant
- atherosclerosis: most frequent*
25
What is an atheratomous plaque
Raised lesion with a soft core of lipid covered by a fibrous cap; can obstruct blood flow, embolize, or increase diffusion distance from lumen to media (causing ischemia of vessel wall which can lead to aneurysm formation)
26
What is the most important independent risk factor for atherosclerosis
Genetics
27
What is the influence of gender on atherosclerosis
- premenopausal women are less likely compared to age matched men
- after menopause, women exceed risk in men
28
What is the function of LDL vs HDL
LDL takes fat into tissues, HDL takes it to liver to be processed
29
What can raise HDL levels
Exercise and moderate consumption of alcohol *obesity and smoking lower it
30
What is in the necrotic center of atherosclerotic plaque
Cell debris, cholesterol crystals foam cells, calcium
31
What is the most common cause of LVH
Chronic HTN
32
Why is DM a risk for atherosclerosis
Induces hypercholesterolemia
33
Which marker is used to measure inflammation
CRP - marker or risk of MI, stroke, PVD, and sudden cardiac death
34
What are additional risk factors for atherosclerosis
Inflammation, hyperhomocystinemia, metabolic syndrome, lipoprotein a, factors affecting homeostasis
35
What is metabolic syndrome
Insulin resistance, HTN, dyslipidemia (elevated LDL and depressed HDL), hypercoagulability, and proinflammatory state
36
What is lipoprotein a
Altered form of LDL that contains apo B 100 portion of LDL linked to apo A; associated with CV dz risk independent of total cholesterol
37
Describe the progression of atherosclerosis
-endothelial injury and dysfunction causes increased permeability, leukocyte adhesion and thrombosis -> accumulation of lipoproteins in vessel wall -> monocyte adhesion to endothelium followed by migration into intima and transformation into macrophages and foam cells -> platelet adhesion -> factor release from platelets, macrophages induces smooth m cell recruitment -> smooth m proliferates and ECM production and recruitment of T cells -> lipid accumulation
38
What are the 2 most important causes of endothelial dysfunction
Hemodynamic disturbances and hypercholesterolemia
39
What are dyslipoproteinemias
Lipoprotein abnormalities that include: increased LDL, decreased HDL, increased levels of abnormal lipoprotein a; can arise from mutations or as a result of nephrotic syndrome, alcoholism, hypothyroidism, or DM
40
What are the dominant lipid in atheromatous plaques
Cholesterol and cholesterol esters
41
How does hyperlipidemia lead to atherogenesis
- directly impairs endothelial function by increasing ROS production which accelerates NO decay and dampens its vasodilation action
- lipoproteins aggregate in intima and can be oxided by free radicals -> accumulated by macrophages via scavenger receptors -> forms foam cells (smooth m cells can transform into foam cells but they take up lipid via LDL receptor)
42
Describe the inflammatory process in atherosclerosis
Fat in macrophages -> inflammasome -> IL-1 -> recruits leukocytes
43
What converts a fatty streak into a mature atheroma
Intimal smooth m proliferation and ECM deposition
44
Which growth factors are implicated in intimal smooth m proliferation
PDGF, FGF, and TGF alpha
45
Besides pathology, when do you see fatty streaks
Aortas of infants and all adolescents
46
What are the most extensively involved vessels in atherosclerosis
Lower AA, coronary aa, popliteal, internal carotid aa, and vessels of circle of Willis
47
What are the components of atherosclerotic plaques
- smooth m cells, macrophages, T cells
- ECM, collagen, elastic fibers, and proteoglycans
- intracelllular and extracellular lipid.
48
What pathological changes are atherosclerotic plaques susceptible to
- rupture, ulceration or erosion -> exposes highly t hrombogenic substances and leads to thrombosis
- hemorrhage into a plaque: rupture of overlying fibrous cap or of the thin walled vessels in the areas of neovascularization
- atheroembolism
- aneurysm formation: induced pressure or ischemic atrophy of underlying media with loss of elastic tissue
49
What does “Eccentric” mean when describing plaques
Does not cover whole wall
50
The arteries that are most often the targets of atherosclerosis have what properties
Large elastic or large and medium sized muscular
51
What preserves the size of the lumen early on in atherosclerosis
Media remodeling
52
What is critical stenosis
Stage at which the occlusion is sufficiently severe to produce tissue ischemia
53
What are the categories of plaque changes
- rupture/fissuring
- erosion/ulceration
- hemorrhage into atheroma (expands its volume)
54
Which kinds of plaques are more likely to rupture
Those that contain large areas of foam cells and extracellular lipid and those in which the fibrous caps are thin or contain few smooth mm cells or have cluster of inflammatory cells - referred to as vulnerable plaques
55
What is the main component of the fibrous cap
Collagen (produced by smooth mm cells) - more collagen, more stable
56
How can vasoconstriction at sites of atheroma be stimulated
Adrenergic agonists, locally released platelet contents, endothelial cell dysfunction with impaired secretion of endothelial derived relaxing factors, mediators released from perivascular inflammatory cells
57
What is a false aneurysm
Defect in the vascular wall leadin to an extravascular hematoma that freely communicates with the intravascular space (pulsating hematoma) ie: ventricular rupture after MI or a leak at the sutured junction of a vascular graft
58
What are examples of true aneurysms
Atherosclerotic, syphiliti, congenital, ventricular that follow transmural MI
59
What is an arterial dissection
Arises when blood meters a defect in the arterial wall and tunnels between its layers ; often but not always aneurysmal
60
What are saccular aneurysms
Spherical outpourings involving only a portion of vessel wall; often contain thrombus
61
What is a fusiform aneurysms
Diffuse, circumferential ligation of long vascular segment; can involve extensive portions of aortic arch, ab aorta, or iliac; not specific for any dz
62
What happens in Marfan
Defective synthesis of fibrillin leads to aberrant TGF beta activity and weakening of elastic tissue
63
What is loeys-dietz syndrome
Mutations in TGF beta receptors lead to defective synthesis of elastin and collagens I and III which leads to aneurysms
64
Which collagen is defective in ehlers danlos
III
65
How does inflammation lead to aneurysms
Macrophages release MMP which breaks down collagen; *AAA associated with release of IL-4 and IL-10 that stimulate release of MMP from macrophages
66
What. can abuse outer medial ischemia
Atherosclerosis, HTN (narrowing of vaso vasorum) -> leads to degenerative changes such as smooth m cell loss (histo: cystic medial degeneration)
67
How does syphilis cause aneurysms
Obliterative endareritis of vasa vasorum of the thoracic aorta
68
Which is the most common causes of AAA vs ascending aorta aneurysms
AAA: atherosclerosis
| Ascending aorta: HTN
69
What are the cystic spaces of cystic medial degeneration filled with
Proteoglycans
70
What is the morphology of AAA
Saccular or fusiform; can occlude renal, SMA, or IMA by thrombus, can be accompanied by smaller aneurysms in iliac aa
71
What are the AAA variants
- inflammatory: occur in younger patients who present with bak pain and elevated inflammatory markers lots of macrophages associated with dense periaortic scarring that extension to anterior retroperitoneum
- subset of inflamm AAA associated with IgG4 related dz; *responds well to steroids
- mycotic AAA: lesions that have become infected by lodging of circulation of microorganisms
72
What arteries can AAA block
Renal, mesenteric, vertebral (SC), or iliac
73
What is someone with AAA also at risk for
IHD and stroke
74
How can thoracic aortic aneurysms present
Respiratory difficulties, difficulty in swallowing, persistent cough due to compression of recurrent laryngeal ns, pain caused by erosion of bone, cardiac dz (leads to aortic valve dilation with valvular insufficiency or narrowing of the coronary Ostia), rupture
75
What do most people of syphilitic aneurysms die of
Heart failure secondary to aortic valvular incompetence
76
Who does aortic dissection occur in
- Men aged 40-60 with antecedent HTN
| - younger adults with systemic or localized abnormalities of connective tissue affecting the aorta
77
What is the major risk factor for aortic dissection
HTN; aortas of HTN patients have medial hypertrophy of vasa vasorum associated with loss of smooth m
78
Where does the tear occur in most spontaneous aortic dissections
Ascending aorta; usually transverse; can rupture through adventitia causing massive hemorrhage or cardiac tamponade
79
What is a double barreled aorta
When there are 2 tears and the blood flows back into the aorta; can become *chronic dissection
80
Where are the most serious dissections located
Between aortic valve an distal arch
81
What are the classifications of aortic dissections
- Type A: more common and dangerous; proximal lesions involving either both the ascending and descending aorta (Debakey I)or just the ascending (Debakey II)
- Type B: distal lesions not involving the ascending aorta and usually beginning distal to subclavian a (Debakey type III)
82
Involvement of the spinal aa in aortic dissection can cause what
Transverse myelitis
83
Which aortic dissection can be managed conservatively
Type B; tx with anti-HTN
84
What are the clinical manifestations of Vasculitis
Fever, myalgia, arthralgias, malaise
85
What vessels does Vasculitis usually affect
Small vessels
86
What are the 2 common pathogenic mechanisms of Vasculitis
Immune mediated inflammation and direct invasion of vascular walls by infectious pathogens
87
What arteries does giant cell arteritis affect
Aorta, medium sized aa; lymphocytes and macrophages present +/- granulomas, +/- thrombosis, no ANCA,
88
What arteries does granulomatosis with polyangiitis affect
Medium and small sized aa; lymphocytes, macrophages, neutrophils and sometimes eosinophils present *granulomas are required; +/- giant cells and thrombosis; serum ANCA positivity
89
What areteries does churg-Strauss syndrome effect
Medium and small sized; *eosinophils required; no giant cells; serum ANCA positivity;; clin history: asthma, atopy
90
What arteries does polyarteritis nodosa affect
Small and medium sized
91
What aa does leukocytoclastic Vasculitis affect
Small, capillaries and veins; no granulomas, giant cells or serum ANCA positivity
92
What aa does burger dz affect
Medium, small and veins; *thrombosis required; clin hx: young male smoker
93
What aa does Behcet dz affect
Everything except the aorta; *neutrophils requried; no granulomas, giant cells, or serum ANCA positivity; clin hx: orogenital ulcers
94
What can cause immune injury in non-infectious Vasculitis
Immune complex deposition, ANCA, anti-endothelial cell abs, autoreactive T cells
95
What are examples of immune complex associated Vasculitis
- SLE
- drug hypersensitivity reactions; drugs bin to serum proteins or vessel walls; can be mild or severe and fatal; skin lesions most common
- Vasculitis secondary to infections: abs to organisms can form immune complexes that deposit in vascular lesions; polyarteritis nodosa (hep B)
96
What is large vessel Vasculitis usually a result of
Granulomatous dz (giant cell and Takayasu)
97
What are the 2 types of ANCA
- anti-proteinase 3 (PR3-ANCA): neutrophil azurophilic granule constituent; associated with polyangiitis
- anti-myeloperoxidase (MPO-ANCA) lysosomal granule involved in oxygen free radical generation; induced by propylthiouracil; associated with polyangiitis and churg-Strauss syndroem
98
Do ANCA abs form circulating immune complexes
No *pauci immune - do not have any demonstrable complement
99
What Vasculitis do abs to endothelial cells produce
Kawasaki d
100
What is giant cell arteritis
Chronic inflammatory disorder of large to small sized aa that principally affects arteries in the head (temporal, vertebral and ophthalmic aa) -> latter can lead to blindness; *medical emergency
101
What is the pathogenesis of giant cell arteritis
T cell mediated immune response against vessel wall a antigens -> TNF release; responds to steroids
102
What is the morphology of giant cell arteritis
Intimal thickening that reduces diameter; medial granulomatous inflammation that produces elastic lamina fragmentation; T cell and macrophage infiltrate
103
What are the clinical features of giant cell arteritis
> 50; fever, fatigue, weight loss; facial pain or HA; to dx need to bx at least 1 cm segment; tx with steroids or anti-TNF
104
What is takayasu arteritis
Granulomatous Vasculitis of medium and larger arteries; characterized by ocular disturbances and weak in go pulses in upper extremities (pulseless dz); transmural thinking of aorta; younger than 50
105
What is the morphology of takayasu arteritis
Classically involved aortic arch; pulmonary a and coronary and renal aa can also be affected; intimal hyperplasia; histo indistinguishable from giant cell arteritis
106
What are the clinical features of takayasu arteritis
Reduced BP and weak pulses in carotid and UE ocular disturbances, retinal hemorrhages, neuro deficits; claudication; pulm a involvement can lead to pulm HTN;; coronary involvement -> MI;; Renal aa -> systemic HTn
107
What is polyarteritis nodosa
Systemic Vasculitis of small or medium sized muscular aa; involves renal and visceral vessels but sparing pulmonary; a good percentage have chronic hep and deposits containing HBsAg-HBsAb complex’s
108
What is the morphology of classic polyarteritis nodosa
Segmental transmural necrotizing inflammation of small to medium aa; weakens wall and can lead to aneurysms or rupture; *fibrinoid necrosis
109
What are the clinical features of polyarteritis nodosa
Typically young adults; manifestations result from ischemia and infarction; remitting and episodic; rapidly accelerating HTN, ab pain and bloody stools cause by vascular GI lesions, diffuse myalgia and peripheral neuritis (motor nerves); *renal involvement cause of mortality; if untreated -> fatal
110
What is Kawasaki dz
Acute febrile usually self limited illness of infancy and childhood;; associated with an arteritis affecting large to medium sized and even small vessels; *predilection for coronary involvement that can abuse aneurysms that rupture or thrombosis resulting in acute MI *leading cause of acquired heart dz in children
111
What are the clinical features of Kawasaki dz
Conjunctival and oral erythema and blistering, edema of hands and feet, erythema of palms and soles, desquamative rash, and cervical LAD (aka mucocutaneous LN syndrome) tx with IV immunoglobulins and aspirin
112
What is microscopic pollyangiitis
Necrotizing Vasculitis that generally affects capillaries as well as small arterioles and venules; aka hypersensitivity Vasculitis or leukocytoclastic Vasculitis; *all lesions tend to be of the same age in any given patient and are distributed more widely (diff from polyarteritis nodosa); necrotizing glomerulonephritis and pulm capillaries are common; can be a feature of henoch-schooling’s purpura, essential mixed cryoglobulinemia
113
What are most cases of microscopic polyangiitis associated with
MPO-ANCA
114
What is the morphology of microscopic polyangiitis
Segmental fibrinoid necrosis of media and focal transmural necrotizing lesions; no granulomas;spare medium sized and larger areteries; infarcts are uncommon
115
What are the clinical features of microscopic polyangiitis
Hemoptysis, hematuria and proteinuria, bowel pain or bleeding, m pain or weakness, and palpable cutaneous purpura; immunosuppression is tx
116
What is churg-Strauss syndrome
Small vessel necrotizing Vasculitis associated with asthma, allergic rhinitis, lung infiltrates, peripheral hypereosinophilia, and extravascular necrotizing granulomata; multi system dz with cutaneous involvement (palpable purpura), GI blueing, renal dz (focal and segmental glomerulosclerosis), MI (cardiomyopathy) *accounts for most deaths
117
What is behcet dz
Small to medium vessel neutrophilic Vasculitis that classically presents as clinical triad of recurrent oral aphthous ulcers, genital ulcers, and uveitis; can also be GI and pulm manifestations with dz mortality related to severe neuro involvement or rupture of vascular aneurysms; *assoc with HLAB51 tx w/ steroids or anti-TNF
118
What is granulomatosis with polyangiitis
Necrotizing Vasculitis characterized by triad of: necrotizing granulomas of upper respiratory tract or lower respiratory tract, necrotizing granulomatous Vasculitis of small to edit vessels most prominent in lungs and upper airway, and focal necrotizing often crescentic glomerulonephritis
119
What is the pathogenesis of granulomatosis with polyangiitis
Form of T cell mediated hypersensitivity response to normally innocuous inhaled microbial or environmental agents *PR3-ANCAs; PR3-ANCA titer used to follow disease after therapy
120
What is the morphology of granulomatosis with polyangiitis
Upper respiratory tract lesions range from inflammatory sinusitis with mucosal granulomas to lucrative lesions; necrotizing granulomas surrounded by zone of proliferating fibroblasts associated with giant cells and leukocytic infiltrate; can cavitate
121
What are the clinical features of granulomatosis with polyangiitis
Males more than males; avg age is 40; persistent pneumonitis with b/l nodular and caviar infiltrates, chronic sinusitis, mucosal ulceration of nasopharynx and renal dz; untreated it is rapidly fatal within 1 year; tx with steroids, cyclophosphamide and anti TNF -> turns it into chronic relapsing and remitting dz
122
What is thromboangiitis obliterates (buerger dz)
Segmental thrombosing acute and chronic inflammation of medium sized and small aa (mainly the trial and radial aa) with occasional secondary extension to veins and nerves of the extremities; leads to vascular insufficiency of the extremities *occurs exclusively in heavy cig smokers usually before age 35
123
What is the pathogenesis of buerger dz
Either direct endothelial cell toxicity from smoke or immune response to components of tobacco smoke; patients vessels exhibit impaired endothelium-dependent vasodilation when challenged with Ach; incrased prevlence in israeli, Indian, and Japanese
124
What is the morphology of thromboangiitis obliterans
Focal acute and chronic vasculitis of small and medium sized arteries; luminal thrombosis containing microabscesses
125
What are the clinical features of thromboangiitis obliterans
Cold induced raynaud initiallly, intermittent claudication, instep foot pain induced by exercise (instep claudication), and superficial nodular phlebitis (venous inflammation); eventually pain at rest due to neural involvement; chronic ulcers develop -> frank gangrene; smoking cessation early on can help but once established, doesn’t help
126
What do the affected areas of raynaud look like
“Red white and blue” from proximal to distal; caused by proximal vasodilation, central vasoconstriction, and distal cyanosis
127
Who does primary raynaud most commonly affect
Young women; symmetrically affects extremities; chronicity can lead to atrophy of the skin, subcutaneous tissues, and mm
128
What is secondary raynaud phenomenon
Vascular insufficiency due to arterial dz caused by entities such as SLE, scleroderma, Buerger dz, or atherosclerosis; *asymmetric involvement of extremities and worsens over time
129
What mediators can cause prolonged myocardial vessel contraction
Endogenous: epi by a pheochromocytoma; thyroid hormone increases sensitivity to catecholamines
Exogenous: cocaine or phenylephrine
Autoabs an Tcells in scleroderma can cause vascular instability and vasospasm
130
What is takotsubo cardiomyopathy
Ischemic dilated cardiomyopathy; also all’s broken heart syndrome because of association with emotional duress
131
What is the histo of myocardial vessel vasospasm
Acute cases show microscopic areas of necrosis characterize by myocyte hypercontraction (contraction band necrosis); subacute and chronic exhibit micro OCP of granulation tissue or scar
132
Why does obesity and pregnancy cases varicosity
Impedes venous draining by mass effect
133
What is stasis dermatitis
Secondary tissue ischemia from varicose veins and leads to stasis dermatitis aka brawny induction; brawny color comes from hemolysis; also leads to ulceration, poor wound healing and superimpose infections
134
What is thrombophlebitis and phlebothrombosis
Interchangeable destinations for venous thrombosis and inflammation
135
What is superior vena cava syndrome
Usually caused by neoplasms t hat compress or invade the SVC (ie bronchogenic carcinoma or mediastinal lymphoma); produces clinical complex including marked dilation of vins of the head, neck and arms with cyanosis; pulm vessels can be compressed and lead to resp distress
136
What is the inferior vena cava syndrome
Caused by neoplasms that compress or invade IVC or by thrombosis of hepatic, renal, or LE veins that propagates cephalad; HCC and RCC* causes LE edema, distention of superficial collateral veins of lower abdomen and with renal involvement causes massive proteinuria
137
What is the most common cause of lymphangitis
Group A beta hemolytic strep; lymph is dilated and filled with exudate of neutrophils and monocyte -> can produce cellulitis or focal abscesses
138
What is lymphadenitis
Painful swelling of LN
139
What is primary lymphedema
Can occur as isolated congenital defect or as familial Milroy dz which results in lymphatic agenesis or hypoplasia
140
What is secondary lymphedema
Aka obstructive; blockage of normal lymphatic
- tumors
- surgery that removes groups of LN
- post radiation fibrosis
- filariasis
- postinflammatory thrombosis and scarring
141
What does lymphedema lead to
Peau d’orange appearance of overlying skin; ulcers can develop; rupture of dilated lymphatics leads to milky accumulations of lymph designated as chylous ascites, chylothorax, and chylopericardium
142
What are the vascular tumors
- endothelial derived: hemangioma, lymphangioma, angiosarcoma
- arise from cells that support or surround bv: glomus tumor, hemangiopericytoma
- primary tumors of large vessels are connective tissue sarcomas
143
How can you distinguish between benign and malignant vascular tumors
- benign usually produce obvious vascular channels filled with blood cells lined by a mono layer of normal appearing endothelial cells
- malignant tumors are more cellular and more proliferative; exhibit cytologic atypia; do not form well organized vessels noirs with histo of endothelial cell specific markers such as CD31 or vWF
144
What is a vascular ectasia
Any local dilation of a structure; telangiectasia is a permanent ligation of preexisting small vessels that form a red lesion
145
What is nevus flammeus
Birthmark; most common form of vascular ectasia; light pink to deep purple flat lesion on had or neck compose of dilated vessels; most regress
146
What is a port wine stain
Special form of nevus flammeus; tends to grow during childhood, thicken the skin surface and does not fade with time; if distributed in trigem n -> sturge-Weber syndrome aka encephalotrigeminal angiomatosis which is associated with ipsilateral venous angiomas in cortical leptomeninges, mental retardation, seizures, hemiplegia, and skull radioopoacities
147
What are spider telangiectasia s
Nonneoplastic vascular lesions resembling a spider; dilated subcutaneous aa or arterioles bout a central core that blanch with pressure; assoc with hyperestrogenic states
148
What is hereditary hemorrhagic telangiectasia
Osler-Weber-rendu dz; AD; caused by mutations in genes that encode TGF beta signaling; telangiectasia present at birth over skin, respiratory tract, GI, and urinary tract; can spontaneously rupture causing serious epistaxis, GI bleeed or hematuria
149
What is angiomatosis
When hemangioma are more extensive than head and neck
150
Where do most internal hemangiomas form
Liver
151
What are capillary hemangiomas
Most common type of hemangiomas; occur in skin, subcutaneous tissue and mucous membranes of oral cavities and lips as well as in liver, spleen, and kidneys; histo thin-walled cap with scant stroma
152
What are juvenile hemangiomas
Strawberry type; of the newborn; extremely common; arise in skin and grow rapidly for a few months but then fade by 1-3 years and completely regress by 7
153
What are cavernous hemangiomas
Large dilated vascular channels; more infiltrative than cap hemangiomas; frequently involve deep structures and do not spontaneously regress; histo: unencapsulated, infiltrative borders, compose of large blood-filled vascular spaces separated by contrive tissue stroma; thrombosis and dystrophic calcification is common; *componenet of VHL dz (found in cerebellum, brain stem, retina, pancreas, and liver)
154
What are pyogenic granulomas
Capillary hemangiomas that present as rapidly growing e pedunculated lesions on the skin, gingival, or oral mucosa; bleed easily and often ulcerate; some develop after trauma; curettage and cautery curative *pregnancy tumor (granuloma gravidarum) is a pyogenic granuloma
155
What are lymphangiomas
Benign lymphatic counterparts of hemangiomas
156
What are simple capillary lymphangiomas
Slightly elevated occur in head, neck, and axillary subcutaneous tissues; histo: networks of endothelium lined spaces that can be distinguished from cap by lack of red cells
157
What are cavernous lymphangiomas
Aka cystic hygrometer; typically found in neck or axilla of children and more rarely in the retroperitoneum; *turner
158
What is glomus tumor
Aka glomangioma; benign but very painful; arise from modified smooth mm cells of glomus bodies (AV structures involved in thermoregulation); most common in distal portion o the digits especially under fingernails; excision is curative
159
What is bacillary angiomatosis
Vascular proliferation in immunocompromised hosts caused by opportunistic gram negative bacilli of the bartonella family - bartonella henselae and bartonella Quintana (transferred by lice)
160
What is the morphology of bacillary angiomatosis
Skin lesions are red papules or nodules; histo: cap proliferation with prominent epithelioid endothelial cells exhibiting nuclear atypia and mitosis lesions contain stromal neutrophils, nuclear dust and causal bacteria
161
What causes the vascular proliferation from B henselae
Induction of HIF by the bacteria -> VEGF; infection cleared by macrolide abx (erythromycin)
162
What is classic kaposi sarcoma
Disorder of older men of Mediterranean, middle eastern or Eastern European; uncommon in US; associated with malignancy or altered immunity but NOT with HIV; multiple red-purpose skin plaques in distal LE; increase in size and number and spread proximally; typically asymptomatic nd remain localized to skin and subcutaneous tissue
163
What is endemic African kaposi sarcoma
Occurs in HIV negative individuals younger than 40 and can follow a benign or aggressive course involves LN; most common tumor in africa; prognosis is very poor
164
What is transplant associated kaposi sarcoma
Occurs in solid organ transplant recipients in setting of T cell immunosuppression; pursues aggressive course that involves LN, mucosa and viscera; cutaneous lesions may be absent; lesions regress with attenuation of immunosuppression
165
Do AIDS patients usually die of KS
No - usually of opportunistic infection
166
What is the morphology of kaposi sarcoma
Progression through 3 stages
- patches in LE histo shows only dilated irregular endothelial cell lined vascular spaces with interspersed lymphocytes, plasma cells, and macrophages
- spread proximally, become larger, raised plaques; made of dermal accumulations of dilated jagged vascular handles lined by spindle cells
- eventually becomes nodular; composed of plump proliferating spindle cells encompassing vessels and slitlike spaces containing red cells
167
How do you tx classic kaposi sarcoma
Surgical resection
168
What are hemangioendotheliomas
Spectrum of vascular neoplasms with clinical behaviors intermediate between benign well-diff hemangiomas an anaplastic angiosarcomas
169
What is epitheloid hemangioendothelioma
Vascular tumor of adults occurring around medium and large veins most cured by excision, but can recur, met, and patients can die of the tumor
170
What is angiosarcoma
Malignant endothelial neoplasm that affects mainly cults; equal gender predilection; most often affects skin, soft tissue, breast and liver
171
What is hepatic angiosarcoma associated with
Exposure to arsenic, thorotrast (radioactive contrast), polyvinyl chloride (plastic)
172
What is lymphangiosaroma
A type of angiosarcoma that an arise in the setting of lymphedmema (classically in ipsilateral UE after radical mastectomy)
173
What is the morphology of angiosarcoma
Gross: start as red papules; eventually become large fleshy masses of red-tan to gray-white tissue with margins blurring into surrounding structures; central areas of hem and necrosis are common
-histo: all degrees of diff can be seen (CD31 or vWF markers)
174
What are hemangiopericytomas
Thought to aris from pericytes, but now believed to be derived from fibroblasts; ie: solitary fibrous tumor that arises on pleura
175
How does endovascular angioplasty and stenting work
Inflating a balloon catheter to pressures sufficient to rupture the occluding plaque (angioplasty) and inducing a limited arterial dissection; most now accompanied by stenting to avoid reclosure by compression of lumen from extensive dissection, vessel all spasm or thrombosis
176
What are coronary stents
Expandable tubes of metallic mesh; thrombosis is complication -> patients must receive potent antithrombitc agents (anti-platelets)
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Which drugs coat stent
Paclitaxel or sirolimus; if used require extended course of anticoagulation
178
Where can grafts be taken for vascular replacement
Saphenous vein or left internal mammary arteries; mammary arteries stay patent longer
179
What does it mean if Lead I is negative on and EKG
Right axis deviation; aVF can be positive or negative; right ventricular hypertrophy
180
What does it man if lead I is positive but aVF is negative
Left axis deviation; left ventricular hypertrophy
181
What drugs are nitrates
Nitroglycerin, isosorbide dinitrate, isosorie mononitrate
182
Which drugs are calcium channel blockers
- non-cardioactive: amlodipine, nifedipine, nicardipine
| - cardioactive:: dilitiazem and verapamil
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Which drugs are useful in treating variant (vasospastic or prinzmetal) angina
Drugs that increase coronary blood flow
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What do drugs that increase coronary blood flow cause in classic angina
Coronary steal phenomenon - redistribution of blood to non-ischemic areas because of dilation of small arterioles ie: dipyridamole
185
How is NO produced from the endothelium
Ach/bradykinin/substance P binds to receptor -> increases calcium -> binds to calmodulin -> activates NOS -> produces NO
186
How to nitrates work
Metabolically activated to NO which converted GTP to cGMP -> activates protein kinase G -> opens potassium handles and hyperpolarizes cell and reduces calcium entry; also dephosphorylates myosin light chain leading to smooth m relaxation
187
What are the pharmacokinetics of nitrovasodilators
- significant first pass metabolism (high nitrate reductase in the liver)
- bioavailability PO is low
- other routes that avoid first pass are use
- partially denitrated metabolites may have activity Nd longer half lives
- isosorbide mononitrate is a poor substrate of nitrate reductase *higher bioavailability
188
What is needed to release NO from nitrates
Thiol compounds *significance of ADH2
189
What dose NO dilate
Mostly veins; larger concentrations -> large aa *no coronary steal; also inhibits platelet aggregation
190
What is the MOA of nitrates in classic vs variant angina
classic: Decreases myocardial oxygen demand
-dilation of veins reduces preload
-if given enough to dilate aa can reduce after load
Variant: coronary a dilation
191
What are the effects of NO besides vasodilation
Inhibits platelet aggregation, inhibits monocyte adhesion, inhibits smooth m proliferation, inhibits superoxide radical, inhibits LDL oxidation
192
How can tolerance to nitrates develop
Depletion of thiol compounds, increased generation of superoxide radicals (combines with NO to make hydrogen peroxide or peroxynitrate), reflex activation of sympathetic n system (tachycardia), retention of salt and water
193
What are the short acting vs long acting doses of nitrates
- short acting: nitroglycerin or isosorbide dinitrate via sublingual or spray
- long acting: nitroglycerin via oral, ointment, or patch (lasts the longest); isosorbide dinitrate and mononitrate orally
194
What are the side effects of nitrates
- HA (meningeal vasodilation *contraindicated if ICP elevated)
- orthostatic hypotension
- increased symp discharge
- increased renal Na an H2O reabsorption
195
Which calcium channel blocker is long acting
Amlodipine
196
What is the downstream effect of calcium channel blockers
Inhibits the activation of myosin LC kinase by Ca-calmodulin complex -> therefore cannot phosphorylate myosin LC and there is no contraction
197
What is the difference between dihydropyridines and cardioactive CCBs
Cardioactive decrease cardiac contractility, decrease automaticity of SA node, and decrease conduction
198
How do CCBs work in classic vs variant angina
- classic: dilation of peripheral arterioles -> decreases PVR and afterload *dihydropyridines most potent; also decreases contractility and HR
- variant: dilates coronary aa which relieves local spasm
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What are the side effects of CCBs
- cardiac depression, cardiac arrest, acute heart failure
- bradycardia, AV block
- short acting dihydropyridines cause sympathetic activation via reflex
- nifedipine increases risk of MI in patients with HTN (give slow release and long acting to these patients)
- peripheral edema, constipation
200
Which beta blockers are used to treat angina
Propranolol, nadolol, metoprolol, atenolol
201
What is the MOA of beta blockers in angina
Decrease oxygen demand; reduced afterload, decreased HR
202
What are the side effects of beta blockers
Broncospasm, impaired liver glucose mobilization, increases VLDL and decreases HDL, sedation and depression, withdrawal syndrome
203
What are contrainditions to beta blockers
Asthma, PVD, T1DM on insulin, Brady Arrhythmias and AV conduction abnormalities, severe depression of cardiac function
204
What are the undesirable effects of beta blockers and calcium channel blockers when use alone
Increase in end diastolic volume and ejection time
205
What is the effect of combining nitrates with CCBs or beta blockers
Decreased HR, decreased arterial pressure, no change or decreased end diastolic volume, no change in contractility, no change in ejection time
206
What is ranolazine
Inhibits late Na+ current in cardiomyocytes
-ischemic myocardium is often partially depolarized - late Na current is enhanced in ischemia and brings Ca overload; ranolazine normalizes repolarization *does not effect HR, coronary blood flow, and peripheral hemodynamics
207
When is ranolazine used
Stable angina that is refractory to medication; improves exercise tolerance in those taking other medications
208
What is the first line drug for treatment of variant angina
CCBs; if contraindicated give long acting nitrate
209
What is the approach to treating stable angina
First give lipid lowering therapy, lifestyle modifications, immediate release nitrates and anti platelet -> beta blocker or alternative (CCB or LA nitrate) -> add CCB or BB if not first drug (if low BP, give LA nitrate or ranolazine) -> consider triple therapy -> consider CABG surgery
210
What does the coordinating beating of cardiac myocytes depend on
Intercalated discs: facilitate cell-cell mechanical coupling
211
What is the architecture of cardiac valves
- dense collagenous core (fibrosa) at the outflow surface and connected to valvular supporting structures - responsible for integrity of valve
- central core of loose connective tissue (spongiosa)
- layer rich in elastin (ventricularis or atrialis) on the inflow surface - important for valve closure
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What do valvular interstitial cell do
Synthesize ECM and express matrix degrading enzymes
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What are the types of pathological changes to valves
- damage to collagen that weakens the leaflets (mitral valve prolapse)
- nodular calcification beginning in interstitial cells
- fibrotic thickening (rheumatic heart dz)
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What is the function of the AV node
Makes sure atrial contraction occurs before ventricular systole
215
What process do cardiac myocytes rely on for energy
OxPhos
216
What are the 3 major epicardial coronary aa
Left anterior descending (LAD) and left circumflex (LC) aa arise from left coronary a; right coronary a
217
What are the divisions of LAD vs LCX
LAD: diagonal
LCX: marginal
218
What is basophils degeneration
Gray-blue byproduct of glycogen metabolism within cardiac myocytes; increases with Ge
219
What happens to the size of the left ventricular cavity with age
Reduces; exacerbated by HTN and bulging of basal ventricular septum into let ventricular outflow track (sigmoid septum)
220
What can valvular changes as we age lead to
A fib (dilates the atrium)
221
What are lambl excrescences
Small filiform processes that form on lines of aortic and mitral valves probably resulting from organization of small. Thrombi
222
Why does the aorta become thicker with age
Increased collagen deposition and loss of elastin
223
What happens to the myocardium with age
Fewer myocytes, increased collagenized connective tissue and deposition of extracellular amyloid (due to poor catabolism of transthyretin)
224
What maintains arterial pressure and organ perfusion when cardiac function is compromised
- frank-starling mechanism: increased filling volumes dilate the heart and increased actin-myosin cross bridge formation, enhancing contractility and stroke volume
- myocardial adaptations (hypertrophy with or without cardiac chamber dilation)
- activation of neurohumoral systems (release of norepi, RAAS, and ANP)
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What are some causes of diastolic dysfunction
Left ventricular hypertrophy, myocardial fibrosis, constrictive pericarditis, amyloid deposition; ventricles cant relax and fill properly
226
What can cause hypertrophy
Increase in mechanical work due to pressure overload or trophic signals (beta adrenergic)
227
What do hypertrophic cells look like
Increased protein synthesis, increased size of nuclei (increased DNA ploidy bc increased replication without cell division)
228
What do the myocytes of pressure overload hypertrophy look like
(Due to HTN or aortic stenosis); new saromeres are assembled in parallel expanding the cross sectional area of myocytes
229
What do the myocytes look lik in volume-overload hypertrophy
New sarcomeres assembled in series within existing sarcomeres leading to ventricular dilation
230
What is the best measure of hypertrophy in dilated hearts
Weight rather than wall thickness
231
What are the molecular change seen in hypertrophy
Expression of FOS, JUN, MYC, ER1; chronic: see fetal heart expression (beta-myosin heavy chain)
232
What is non pathologic hypertrophy of the heart
Induced by exercise *special because has increases in capillary density so the hypertrophic parts receive blood supply; and decreases in resting HR and blood pressure
233
What causes left sided heart failure
Ischemic heart dz, HTN, aortic and mitral valvular diseases, primary myocardial dz; effects are passive congestion of blood in the pulmonary circulation, stasis of blood in the left sided chambers, and inadequate perfusion
234
What does left sided heart failure increase the risk of
A fib and mural thrombus
235
What are the pulmonary changes seen in left sided heart failure
(From mildest to most severe) perivascular and interstitial edema (Kerley B and C lines), progressive edematous widening of alveolar septa, accumulation of edema in alveolar spaces *some red cells extravate into edema in alveolar spaces and are digested by macrophages to form hemosiderin laden macrophages (heart failure cells)
236
What are the initial symptoms of CHF
Pulmonary; dyspnea and cough; as it progresses, can cause orthopnea (can’t breath when laying down), paroxysmal nocturnal dyspnea
237
What does CHF do to the kidneys
Decrease renal perfusion activates RAAS -> exacerbates pulm edema; azotemia
238
What can advanced CHF do to the brain
Hypoxic encephalopathy - irritability, loss of attention, restlessness that can progress to stupor and coma
239
What is the difference between systolic and diastolic left sided heart failure
- systolic insufficient ejection fraction
- diastolic: left ventricle is stif and cannot relax; unable to increase output in response to increases in metabolic demands; because ventricle cannot hold much blood, pushes it back to pulmonary circulation and causes rapid onset pulm edema (flash pulm edema) *occurs in patients >65 and is more common in women *HTN most common underlying problem; DM, obesity, b/l renal a stenosis can also contribute
240
What is the most common cause of right sided heart failure
Left sided heart failure
241
What causes isolated right heart failure
Cor pulmonale (caused by interstitial lung dz, primary pulm HTN, PE, pulm vasoconstriction ie: sleep apnea or altitude sickness)
242
What is the difference between right side and left side heart failure
Right side is dominated by engorgement of systemic and portal venous system, but has minimal pulmonary congestion
243
What changes does right sided heart failure cause in the liver
Congestion of hepatic and portal vessels causes liver to increase in size (congestive hepatomegaly), nutmeg liver, centrilobular necrosis (esp if with left sided failure as well), cardiac cirrhosis (central areas become fibrotic), enlargement of spleen with platelet sequestration
244
What does right sided heart failure do to pleural, pericardial and peritoneal spaces
Systemic venous congestion leads to fluid accumulation in these spaces (effusion or ascites)
245
What does right sided failure do to the kidneys
More significant azotemia than left sided;
246
What is the most common type of pediatric heart dz
Congenital
247
What do the first and second heart fields become
First: left ventricle
Second: outflow tract, right ventricle and most of atria
248
How are most congenital heart diseases inherited
AD
249
What are GATA4, TBX5, and NKX2-5 mutated in
Atrial and ventricular septal defects
250
What genes are mutated in tetralogy of fallot
ZFPM2 or NKX2.5
251
What genes are mutated in alagille syndrome
JAG1 or NOTCH2
252
What genes are mutated in char syndrome
TFAP2B
253
What gene is mutate in CHARGE syndrome
CHD7 (helicase binding protein)
254
What gene is mutated in digeorge syndrome
TBX1 (TF)
255
What gene is mutated in holt-oram syndrome
TBX5 (TF)
256
What genes are mutated in noonan syndrome
PTPN11, KRAS, SOS1 (signaling)
257
What contributes to the CV abnormalities in mar fans and loeys-dietz syndrome
Hyperactive TGFbeta (fibrillin is a downregulator of it)
258
Which arches develop abnormally in digeorge
4th branchial arch;; 3rd and 4th pouches
259
What are the manifestations of digeorge
Cardiac ab, ab facies, thymic aplasia, cleft palate, hypocalcemia
260
Deletions of TBX1 are associated with what
Mental illness, including schizophrenia
261
What i hypertrophic osteoarthopathy
Clubbing of fingers and toes resulting from long standing cyanosis (from right to left shunt); also causes polycythemia
262
What ar the causes of right to left shunts
Tetralogy of fallot, transposition of the great arteries, persistent truncus arteriosus, tricuspid atresia, and total anomalous pulmonary venous connection
263
What do left to right shunts cause
Pulmonary capillary and venous pressures increase which causes medial hypertrophy Nd vasoconstriction -> atherosclerosis right ventricle also undergoes hypertrophy; eventually the pulm resistance approaches systemic less and the original left to right shunt becomes right to left shunt that introduces poorly O2 blood into the systemic circulation (eisenmenger syndrome)
264
What are the obstructive congenital heart diseases
Coarctation of the aorta, aortic valvular stenosis, and pulmonary valvular stenosis; complete obstruction is all an atresia
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Are left to right or right to left shunts more common
Left to right; ASD, VSD, PDA
266
Which volumes does ASD vs VSD and PDA increase
ASD just right ventricular and pulmonary outflow
| VSD and PDA: pulmonary blood flow and pressure
267
When do ASD become symptomatic
Adulthood
268
Describe the development of the interatrial septum
- initially has septum primum and ostium primum
- before septum primum occluded ostium primum it develops a second posterior opening called the ostium secundum
- septum secundum is right and anterior of septum primum, as it grows, it leaves a small opening called foramen o vale that is continuous with ostium secundum; septum secundum grows until it forms a flap of tissue on the left side of foramen ovale
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What is the morphology of ASDs
- Secundum ASD: most common; results from deficient septum secundum formation near the center of atrial septum; usually not associated with another anomalies
- Primum anomalies: adjacent to AV valves and are associated with AV valve abnormalities or VSD
- Sinus venous defers: located near entrance of SVC and associated with anomalous pulm venous return to the right atrium
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What are the clinical features of ASD
Left to right shunt murmur present as a result of increased flow through pulm valve; generally well tolerated; mortality is low
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What kind of shunting can PFO cause
Right to left during increased pulm BP or during a bowel movement, coughing or sneezing
272
What is the most common form of congenital heart dz
VSD
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Where do most VSD occur
Region of membranous IV septum; reminder occur below the pulm valve called infundibular VSD
274
What are the clinical features of VSD
Most that manifest in Peds are assoc with other abnormalities such as ToF; if in an adult, usually isolated; consequences based on size and whether or not there are right sided malformation; cause left to right shunting -> right ventricular hypertrophy and pulm HTN; eventually lead to shunt reversal and death
275
What is the ductus arteriosus
Connection between pulm artery and aorta; allows bypassing of lungs; closes due to increased arterial oxygenation, decreased pulm vascular distance, and declining local levels of prostaglandin E2; failure to close in hypoxic infants or those with VSD (increase pulm vascular pressure)
276
What kind of murmur does PDA produce
Continuous harsh machinery like murmur
277
Is PDA cyanotic
No -> its left to right; however, with large shunts, additional volume and pressure overloads eventually produces obstructive changes in small pulm aa leading to reversal of flow
278
Why would you keep a PDA open
For infants with various ongenital malformations that obstruct pulmonary or systemic outflow tracts; ie: aortic valve atresia
279
What are the right to left shunts
ToF, transposition of great aa, persistent truncus arteriosus, tricuspid atresia, total anaomalous pulmonary venous connection
280
What are the 4 cardinal features of TOF
VSD, obstruction of right ventricular outflow tract (subpulmonary stenosis), aorta that overrides VSD, and right ventricular hypertrophy
*results from anterosuperior displacement of infundibular septum
281
What is the morphology of TOF
Heart is enlarged and boot shaped; VSD is large with aortic valve at the superior border; can have complete atresia of pulm valve *if so, need patent PDA, dilated bronchial aa or both for survival; right aortic arch present in a quarter of cases
282
What does the shunting across the VSD in TOF depend on
Degree of subpulmonary stenosis when severe -> right to left
283
What is pink tetralogy
When subpulmonary stenosis is mild and resembles an isolated VSD no cyanosis
284
What effect does severe subpulmonic stenosis have on the pulm aa and aorta
Pulm aa are hypoplastic and overriding aorta become larger
285
What is transposition of the great aa
Aorta lies anterior and arises from right ventricle and pulm a is posterior Nd comes from left ventricle *stems from ab formation of truncates and aortopulmonary septa; incompatible with life unless corrected or shunt
286
What happens to the ventricles with transposition of the great vessels
Right ventricular hypertrophy and left atrophy
287
What is tricupsid atresia
High mortality; cyanotic; needs a shunt; hypoplastic right ventricle
288
What is coarctation of the aorta
Narrowing of the aorta; more common in males; *females with turner
289
What are the 2 forms of coarctation of the aorta
- infantile: symptomatic in early childhood; tubular hypoplasia of aortic rich proximal to a PDA
- adult: ridgelike unfolding of the aorta opposite the closed ductus arteriosus distal to arch vessels
290
What other anomalies is coarctation of the aorta associated with
Bicuspid aortic valve and congenital aortic stenosis, ASD, VSD, mitral regurgitation, or berry aneurysms of circle of Willis
291
What does the clinical manifestations of coarctation of the aorta depend on
Severity of narrowing and patency of ductus arteriosus;
* coarctation with PDA manifests early in life -> cyanosis localized to lower half of body *do not survive without intervention
* without PDA: most asymptomatic till adulthood; HTN in UE with weak pulses and hypotension in LE *develop collateral circulation btw intercostal and internal mammary aa producing erosions (notching) of the ribs on radiograph
292
When are murmurs present in coarctation of the aorta
Systole; vibratory thrill can sometimes be felt
293
What locations can aortic stenosis occur
Valvular, subvalvular, supravavlular
294
What are the features of valvular aortic stenosis
Cusps can be hypoplasitic, dysplastic (thickened and nodular) or abnormal in number
295
What does congenital forms of aortic stenosis lead to
Hypoplasia of left ventricle and ascending aorta accompanied by Porcelain like left ventricular endocardial fibroelastosis *hypoplastic left heart syndrome; need patent PDA
296
What vitamin is niacin
B3
297
What are the fibric acid derivatives (fibrates)
Fenofibrate and gemfibrozil
298
What are the bile acid sequestrants (resins)
Cholestyramine, colesevelam, colestipol
299
What are the cholesterol absorption inhibitors
Ezetimibe
300
When are dietary measures initiated for management of hyperlipoproteinemia
Initiated first unless has evident coronary a dz or PVD *ppl with familial hypercholesterolemia always require drug intervention in addition to dietary changes
301
Which statin has the highest oral bioavailability
Fluvastatin
302
Which statin has the longest half life
Rosuvstatin
303
Which statins are metabolized by CYP34A
Lovastatin, simastatin, atorvastatin
304
Which statins are metabolized by CYP2C9
Rosuvastatin and fluvastatin
305
Which statins are metabolized by CYP450
Pitavastatin
306
Which statin is not metabolized by CYP450s
Pravastatin
307
What do statins do to LDL receptors
Increase the number; cell has less cholesterol so wants to take it in
308
Which statin is the most potent
Atorvastatin and rosuvastatin
309
What are the benefits of statins
Plaque stabilization, improvement of coronary endothelial function, inhibition of platelet thrombus formation, and anti inflammatory effects
310
When are statins taken
At night because cholesterol synthesis occurs at night except the longer acting atorvastatin, pitavastatin, and rosuvastatin
311
What are the side effects of statins
- liver: elevations of aminotransferase activity
- muscle: CK increase; myopathy increases with dual therapy of statins and fibrates
- statins increase warfarin levels
312
When are statins contraindicated
Pregnancy, lactating, want to become pregnant; not recommended in liver dz or skeletal m myopathy; use in children restricted to homozygous familial hypercholesterolemia and some with heterozygous
313
What are the therapeutic effects of niacin
Decreases TGs, LDL, LP a and increases HDL
314
What are the pharmacokinetics of niacin
Converted to nicotinamide and incorporated into nicontinamide adenine denucleotide (NAD); well absorbed; need 2-3 times a day doses bc short half life
315
What is the MOA of niacin
Inhibits lipolysis of TGs in adipose tissue which reduces circulating FFA -> causes liver to produce less VLDL and LDL; catabolic rate for HDL decreased ; fibrinogen reduced and plasminogen activator levels are increased
316
What are the side effects of niacin
Intense cutaneous flush accompanied by feeling of warmth, pruritus, acanthosis nigricans, hepatotoxicity
317
What are the contraindications of niacin
Avoid in hepatic failure and active peptic ulcer; use in caution with DM (niacin induced insulin resistance)
318
What is the influence of niacin on lipid metabolism
- decreases hormone sensitive lipase which decreases FFA -> decreases TG synthesis in the liver -> decreases VLDL and LDL -> decreases cholesterol delivery to cells
- decreases apoA clearance -> increases plasma HDL -> increases cholesterol delivery to liver -> excretion of chol in bile
319
Which fibrates has a long half life
Fenofibrate
320
What is the MOA of fibrates
Agonists for peroxisome proliferator activated receptor alpha (PPARalpha) nuclear receptor; PPAR binds to DNA which modulates expression of LPL and apoA; increases oxidation of FA in liver and striated m, increases lipolysis of TG via LPL while intracellular lipolysis in adipose tissue is decreased; VLDL decrease
321
When are fibrates useful
Hypertriglyceridemias where VLDL predominates , dysbetalipoproteinemia, and hypertriglyridemia that results from treatment with viral protease inhibitors
322
What are the side effects of fibrates
GI: increased risk of cholelithiasis
Liver: increased serum transaminases
Muscle: myositis (muscle weakness)
Can potentiate actions of anticoagulants
323
What are the contraindications to fibrates
Hepatic or renal dysfunction; safety not established in pregnant or lactating women
324
What is subaortic stenosis
Caused by thickened ring or collar of dense endocardial fibrous tissue below the levels of the caps; associated its systolic murmur and sometimes a thrill; pressure hypertrophy of left ventricle develops; mild stenosis managed with abx prophylaxis to prevent endocarditis and avoidance of strenuous activity; carries risk of sudden death with exertion
325
What is suprvalvular aortic stenosis
Congenital aortic dysplasia with thickening of ascending aortic wall; sometimes results from deletions on chromosome 7 (gene for elastin) - other features include hypercalcemia, cognitive abnormalities, and facial anomalies (williams-Beuren syndrome)
326
Does the heart tolerate ischemia or hypoxia better
Hypoxia
327
How can IHD present
- MI
- angina pectoris
- chronic IHD with heart failure
- sudden cardiac death (SCD)
328
What is a genetic variant that modifies leukotriene B4 metabolism associated with
MI, but not coronary atherosclerosis
329
What are the acute coronary syndromes
Unstable angina, acute MI, and sudden death
330
What is the difference between stable and unstable angina
Stable: not associated with plaque disruption
Unstable: caused by plaque disruption that results in thrombosis and vasoconstriction; microinfarcts can occur
331
What causes sudden cardiac death
Regional myocardial ischemia that induces fatal ventricular arrhythmia
332
What causes the pain felt in angina pectoris
Ischemia induced release of adenosine, bradykinin and other molecules that stimulate sympathetic and vagal afferent nerves
333
What patients does silent ischemia commonly occur in
Elderly and diabetics
334
What is stable angina described as
Deep poorly localized pressure, squeezing, or burning sensation relieved by rest or administering vasodilator
335
What is unstable or crescendo angina described as
Pattern of increasingly frequent prolonged >20 min severe chest discomfort that is described as pain; can occur at rest
336
During what years are women not as likely to get MIs
Reproductive years
337
How do MIs occur
- plaque erodes, ruptures, or hemorrhages
- platelets adhere and release contents to form microthrombi and induce vasospasm
- tissue factor activates coagulation pathway -> occludes vessel
338
In patients where coronary atherothrombosis does not cause the MI, what does?
Vasospasm (sometimes with drugs), emboli (from left atrium in association with a fib, left sided mural thrombus, vegetation’s of infective endocarditis, intracranial prosthetic material or paradoxical emboli), disorders of small intramural coronary vessels (vasulitis), hematologic abnormalities (sickle cell), amyloid deposition, vascular dissection, marked hypertrophy, shock
339
What precipitates heart failure in MI
Loss of contractility long before myocyte death
340
What structural change occur during MI
Myofibrillar relaxation, glycogen depletion, cell and mitochondrial swelling (early; reversible); 20-30 min of ischemia leads to irreversible changes
341
What is the earliest detectable feature of myocyte necrosis
Disruption o integrity of sarcolemmal membrane
342
Where is ischemia most pronounced in the heart
Subendocardium
343
What does the location, size and morphological features of an MI depend on
Location, severity, rate of development of obstruction, size of vascular bed per fused by obstructed vessel, duration of occlusion, metabolic and oxygen needs of the myocardium at risk, extent of collateral circulation
344
What does the LAD branch of the left coronary a supply
Most of the apex of the heart, anterior wall of the left ventricle, and the anterior 2/3 of the ventricular septum
345
What is a right dominant circulation
RCA supplies entire right ventricular free wall, posterobasal wall of the left ventricle and posterior third o ventricular septum LCX perfumes lateral wall of left ventricle
346
Why is there a small area just beneath the endocardium that is spared from necrosis
Can be supplied from diffusion of blood from the ventricle
347
What causes a transmural infarction
Occlusion of epicardial vessel; involves full thickness of ventricular wall
348
What causes a sub endocardial (nontransmural) infarction
Can occur as a result of plaque disruption followed by thrombus that becomes Lysenko before myocardial necrosis extends; can also result from shock superimposed on stenosis (usually circumferential rather than distribution of single artery)
349
What causes multifocal microinfarction
Pathology involving only smaller intramural vessels; can occur with microembolization, vasclitis, or vascular spasm; can lead to sudden cardiac death or ischemic dilated cardiomyopathy (takotsubo cardiomyopathy)
350
What is a transmural infarction referred to as on EKG
ST elevation myocardial infarction (STEMI)
351
What is a subendocardial infarction referred to on and EKG
Non-ST elevation infarction (NSTEMI)
352
What regions do each of the 3 main arteries cause infarction in
- LAD: most common; involves anterior wall of left ventricle near the apex, anterior portion of ventricular septum and the apex circumferentially
- RCA: involves inferior posterior wall of left ventricle, posterior portion of. Ventricular septum and inferior posterior right ventricular free wall
- LCX: involves lateral wall of the left ventricle except the apex
353
What does the gross and microscopic appearance of an MI depend on
Duration of survival of the patient following the MI; death before 12 hours doesn’t show gross changes; if 2-3 hours can see change if immerse tissue slices in triphenyltetrazolium chloride which imparts brick ed color to intact noninfarcted myocardium where lactate DH is preserved - infarcted areas will be pale; 12-24 hrs after can se reddish-blue area caused by trapped blood; 10 days - 2 weeks rimmed by hyperemic zone of granulation tissue
354
What can you see on EM 0-1/2 hours after MI
Relaxation of myofibrils, glycogen loss, mitochondrial swelling; cant see anything on light micro or grossly
355
What can you see on EM 1/2-4 hrs after MI
Sarcolemmal disruption, mitochondrial amorphous densities; nothing on light micro or grossly
356
When can you start to see histo changes of an MI
6-12 hours; wavy fibers at periphery of infarction; myocytolysis (sublethal ischemic Change in the margins of infarcts- accumulation of salt and water within SR)
357
How do MIs heal
From margins toward the center
358
What do reperfused infarcts look like
Hemorrhagic because vasculature is injured during ischemia; micro: contraction bands (intensely eosinophilic intracellular stripes composed of closely packed sarcomeres) resulting from exaggerated contraction when perfusion is reestablished (repercussion salvages reversible injured cells and changes the morphology of lethally injured cells)
359
What is “no-reflow”
When reperfusion injury causes endothelial swelling and blocks ability to reperfuse area
360
What is stunned myocardium
State of prolonged cardiac failure induced by short term ischemia that usually recovers after several days
361
What is hibernation
Myocardium that is subjected to chronic sublethal ischemia -> enters into state of lowered metabolism and function; restored by revascularization
362
What are the clinical features of MI
Chest pain, rapid weak pulse, sweating, N/V (suggested involvement of posterior inferior ventricle with secondary vagal stimulation); dyspnea due to impaired contractility and resultant pulmonary congestion
363
Which lab tests confirm MI
Troponins T and I (cTnT and cTnI) -> begin to rise 3-12 hours after MI (I max at 24 hours) and MB fraction of CK (CK-B) - rises 3-12 hours after and peaks at 24 hours sensitive but not specific b/c can be elevated after skeletal m injury; CK-MB returns to normal in 48-72 hours; I in 5-10 days and T in 5-14 days
364
What factors are associated with a poorer prognosis of an MI
Advanced age, female gender, DM and previous MI
365
What are the therapeutic interventions for MI
Morphine, prompt reperfusion, antiplatelet agents (aspirin, PY12 receptor inhibitors, GPIIb/IIIa inhibitors), anticoagulant therapy with unfractionated heparin, low molecular weight heparin, direct thrombin inhibitors or factor Xa inhibitors, nitrate, beta blockers, antiarrhythmics, ACEI, oxygen supplementation
366
What complications can occur post MI
Contratile dysfunction, Arrhythmias, myocardial rupture, ventricular aneurysm, pericarditis, infarct expansion, mural thrombus, papillary muscle dysfunction, progressive late heart failure
367
What does contractile dysfunction lead to o
Hypotension, pulmonary vascular congestion, interstitial pulm transudates
368
What are the MI associated Arrhythmias
Sinus Bradycardia, a fib, heart block, tachycardia, v fib, ventricular premature contractions, ventricular tachycardia
369
What are the types of myordial rupture
- rupture of ventricular free wall *most common; with hemopericardium and cardiac tamponade; occur 2-4 days after; anterolateral wall at mid-ventricular level is most common site
- rupture of ventricular septum leading to acute VSD and left to right shunting
- rupture of papillary muscle resulting in acute onset of severe mitral regurgitation
370
What are the risk factors for free wall rupture
Older than 60, first MI (less common in previous MI because fibrous scarring), large transmural and anterior MI, absence of LVH, and preexisting HTN
371
What is a ventricular aneurysm
Late complications of large transmural infarcts; scar tissue wall of an aneurysm bulges during systole; complications of aneurysms include mural thrombus, Arrhythmias, and heart failure; rupture doesn’t usually occur
372
What is dressler syndrome
When fibrinoid pericarditis develops following a transmural infarct
373
What are patients with anterior transmural infarcts at greatest risk for
Free wall rupture, expansion, mural thrombi and aneurysm
374
What are posterior transmural infarcts more likely to be complicated by
Conduction blocks, right ventricular involvement
375
What has been shown to lessen ventricular remodeling post MI
ACEI
376
What is chronic IHD
Aka ischemic cardiomyopathy; progressive CHF due to accumulated ischemic myocardial damage and/or inadequate compensatory responses
377
What is the most common cause of rhythm disorders
Ischemic injury
378
What does a damaged SA node lead to
“Sick sinus syndrome” -> AV node tasks over and causes bradycardia
379
What is first degree heart block
Prolongation of P-R interval du to AV node dysfunction
380
What is second degree heart block
Intermittent transmission of signal through AV node
381
What is third degree heart block
Complete failure of AV node
382
What are channelopathies
Mutations in genes required for normal ion channel function that cause congenital Arrhythmias; mostly AD *prototype is long QT syndrome -> susceptible to ventricular Arrhythmias
383
What genes are mutated in long QT syndrome
KCNQ1, KCNH2 (potassium LOF), SCN5A (sodium GOF), CAV3 (caveolin sodium GOF)
384
What genes are mutated in short QT syndrome
KCNQ1 and KCNH2 (both GOF)
385
What genes are mutated in brugada syndrome
SCN5A (Na LOF), CACNB2b (calcium LOF), SCN1b (Na LOF)
Manifests as ST elevation and right bundle branch block; present with syncope or SCD during rest or sleep or after large meals
386
What genes are mutated in CPVT syndrome
RYR2 (diastolic ca GOF), CASQ2 (diastolic ca LOF)
| No ECG changes; stress related Arrhythmias
387
What are the nontherosclerotic causes of SCD
- hereditary or acquired abnormalities of cardiac conduction
- congenital coronary a abnormalities
- mitral valve prolapse
- myocarditis or sarcoidosis
- dilated or hypertrophic cardiomyopathy
- pulm HTN
- myocardial hypertrophy
- pericardial tamponade, PE, catecholamines, cocaine
388
What is the criteria for diagnosis of hypertensive heart dz
- LVH in the absence of other CV pathology
| - clinical history or pathological evidence of HTN in other organs
389
What are the micro changes seen in hypertensive heart dz
Increase in transverse diameter of myocytes; at more advance stage -> cellular and nuclear enlargement accompanied by interstitial fibrosis
390
What happens to the heart as a result of cor pulmonale
Right ventricular hypertrophy of the free wall and dilation; acute cor pulmonale can be caused by PE; *BUT right side heart failure most commonly occurs as a result of left sided dz
391
What is the morophology of acute cor pulmonale
Dilation of right ventricle without hypertrophy
392
What chest movement disorders can cause cor pulmonale
Kyphoscoliosis, obesity (sleep apnea, pickwickian syndrome), neuromuscular disease
393
How do fibrates work
Activate PPAR alpha which 1. Increases FA oxidation in hepatocytes and decreases TG synthesis, 2. Increases LPL expression in m vascular bed which increases FA oxidation in m cells and decreases plasma TG and 3. Increases ApoAI synthesis in hepatocytes which increases plasma HDL
394
What is the MOA of bile acid sequestrants (resins)
Not absorbed; bind to negatively charged bile acids Nd increase bile acid excretion which enhances conversion of cholesterol to bile acids -> decline in cholesterol stimulates increase in LDL receptors *combine with use of a statin because resins us upregulation of HMGCoA reductase
395
What are the side effects of resins
Impair absorption of fat soluble vitamins and certain drugs (tetracycline, phenobarbital, Digoxin, warfarin, pravastatin, fluvastatin, aspirin, and thiazide diuretics) - give these mds one hour before or 2 hours after
396
What are the contraindications to resins
Diverticulitis, preexisting bowel dz or cholestasis
397
What is the only cholesterol absorption inhibitor
Ezetimibe
398
What is the MOA of cholesterol absorption inhibitors
Can inhibit cholesterol reabsorption even in the absence of dietary cholesterol
399
What are cholesterol absorption inhibitors used to treat
Primary hypercholesterolemia; homozygous familial hypercholesterolemia (incombo with atorvastatin or simvastatin), mixed hyperlipidemia in combo with fenofibrate
400
What should you not give with ezetimibe
Bile acid sequesterants -> cant be absorbed
401
Which drug has the most profound effect at increasing HDL
Niacin
402
What is homozygous familial hypercholesterolemia
Mutations in LDL receptors; therefore cannot give reductase inhibitors
403
What is lomitapide
Directly inhibits triglyceride transfer protein (MTP) in the lumen of ER; prevents assembly of apoB containing lipoproteins which reduces the production of chylomicrons and VLDL and reduces LDL; side effects: hepatic fat accumulation; used to treat homo familial hypercholesterolemia
404
What is mipomersen
Antisense oligonucleotide that targets apo B-100 mRNA and disrupts its function (apo B-100 binds LDL to its receptor); injection site reactions (administered subcutaneously 1 x per week), flu like sx, HA, elevated liver enzymes
405
What is functional regurgitation
Incompetence of a valve stemming from an abnormality in one of its support st cultures as opposed to a primary valve defect (ie: dilation of the ventricles can pull the papillary mm own and prevent proper closing)
406
What can exacerbate valve disease
Pregnancy
407
What does valvular stenosis vs insufficiency lead to
Stenosis: pressure overload hypertrophy
Insufficiency: volume overload
408
What are the main causes of valvular lesions
- aortic stenosis: calcification and sclerosis of normal bicuspid aortic valves
- aortic insufficiency dilation of ascending aorta secondary to HTN or aging
- mitral stenosis: rheumatic heart dz
- mitral insufficiency: myxomatous degeneration (mitral valve prolapse)
409
What is deposited in calcific aortic stenosis
Hydroxyapatite
410
What is the treatment for aortic stenosis
Surgical valve replacement
411
What chromosomes are implicated in bicuspid aortic valve
18q, 5q, 13q
412
What is a congenitally bicuspid aortic valve
Only has 2 functional cusps of unequal size with the larger cusp having a midline Raphe (frequent site of calcification deposits); *acquired bicuspid aortic valve can be a result of rheumatic heart dz
413
What are the complications of bicuspid aortic valve
Aortic stenosis or regurgitation, infective endocarditis, aortic dilation or disssetion
414
Where do calcification deposits develop in the mitral valve
Fibrous annulus
415
What can mitral annular calcification lead to
- regurgitation by interfering with physiologic contraction of valve ring
- stenosis by impairing opening of mitral leaflets
- Arrhythmias and sudden death by penetration of calciu deposits that can impinge AV conduction system
416
What are patients with mitral annular calcification at increased risk for
Embolic stroke and infective endocarditis
417
What do mitral calcification look like on radiograph
Ring like opaccities
418
Who is mitral annular calcification most common in
Women older than 60 and individuals with mitral valve prolapse
419
What is another name for mitral valve prolapse
Myxomatous degeneration of the mitral valve
420
What happens during mitral valve prolapse
Leaflets of mitral valve balloon back into left atrium during systole; affects females more than males
421
What is the morphology of mitral valve prolapse
Interchordal balloonin of the mitral leaflets; often enlarged and thick and rubbery; tendinis cords may be elongated, thinned or ruptured; *key histo: thickening of spongiosa layer with deposition of mucoid (myxomatous degeneration)
422
What are the clinical features of mitral valve prolapse
Usually asymptomatic and only caught by mid systolic clicks; confirmed with echo; can have some angina (but not with exertion)
423
What are the complications of mitral valve prolapse e
Infective endocarditis, mitral insufficiency sometimes with chordal rupture, stroke or other systemic infarct (leaflet thrombus), Arrhythmias (ventricular and atrial)
*risk for complications is higher in men, older patients, and those with Arrhythmias and mitral regurgitation
424
How does chronic rheumatic heart disease manifest usually
Valvular abnormalities - particularly the mitral valve *only cause of mitral stenosis
425
What is the morphology of rheumatic heart dz
- acute: Aschoff bodies (T cells and plump activated macrophages called anitschkow cells) *pathognomonic for RF; “caterpillar cells”; found in any of the 3 layers of the heart (pancarditis)
- Inflam of endocardium and left sided valves results in fibrinoid necrosis within the cusps or cords - along which verrucae (vegetation’s) occur
- subendocardial lesions can induce irregular thickenings called MacCallum plaques usually in left atrium
426
What are the anatomic changes of mitral valve in chronic RHD
Leaflet thickening, commisural fusion and shortening, thickening and fusion of cords; always affects mitral; sometimes affects aortic *fish mouth or buttonhole stenosis -> right atrium dilates and can form thrombus *do not see aschoff bodies in chronic RHD
427
What are the clinical features of RF
Migratory polyarteritis of large joints, pancarditis, subcutaeous nodules, erythema marginatum of the skin, syndenham chorea (involuntary rapid movements)
428
What can be detected in the serum of people with RF
Streptolysin O and DNase B
429
What are the clinical features of the acute carditis produced by RF
Pericardial friction rubs, tachycardia, Arrhythmias
430
What is someone at risk for after initial RF attack
Reactivation of the disease with subsequent pharyngeal infections
431
What is infective endocarditis
Microbial infection of the heart valves or mural endocardium that leads to formation of vegetation’s composed of thrombotic debris and organisms
432
What is acute infective endocarditis
Infections of a previously normal heart valve by highly virulent organisms (staph aureus); usually require surgery
433
What is subacute infective endocarditis
Organisms with lower virulence (viridans) that cause infections of demoed valves with less destruction than acute; cured with abx
434
What increases the risk of developing infective endocarditis
RHD, mitral valve prolapse, degenerative calcific valvular stenosis, bicuspid aortic valve, artificial valves, congenital defect
435
What is the HÁČEK group
Haemophilus, actinobacillus, cardiobacterium, eikenella, kingella other bacterial causes of infective endocarditis
436
What causes most causes of infective endocarditis of prosthetic valves
Coagulate negative s epidermidis
437
Where are the most common sites of infection of infective endocarditis
Mitral and aortic valves; right valves involved in IV drug users
438
What are the clinical features of acute endocarditis
Rapidly developing fever, chills, weakness, lassitude; murmurs present in most patients with left sided IE
439
What are the complications of IE
Glomerular antigen ab complex deposition causing glomerulonephritis, microthromboemboli (splinter or subungual hemorrhages), erythematous or hemorrhagic nontener lesions on palms or soles (Jane way lesions), subcutaneous nodules in the pulp of the digits (Osler nodes) and retinal hemorrhages in the eyes (Roth spots)
440
What do noninfected vegetation’s occur in
Nonbacterial thrombotic endocarditis and endocarditis of SLE (libman sacks endocarditis)
441
Where do nonbacterial thrombotic endocarditis vegetation’s deposit
On line off closure of the leaflets or cusps
442
What are the features of libman sakes endocarditis
Mitral and tricuspid valvulitis with small sterile vegetations; warty or versions appearance; histo: granular, fibrinoid eosinophilic material
443
What is carcinoid syndrome
Systemic disorder marked by flushing, diarrhea, dermatitis, and bronhospasm caused by bioactive compounds such as serotonin released by carcinoid tumors; endocardium and valves of right heart primarily affected since the are the first cardiac tissues bathed by mediators released by GI tumors
444
When an left heart carcinoid lesions occur
In set ting of AVD or VSD or primary pulmonary carcinoid tumors
445
What mediators are elaborated by carcinoid tumors
Serotonin, kallikrein, bradykinin, histamine, prostaglandins, and tachykinins
446
What correlates with the severity of cardiac lesions found in carcinoid syndrome
Plasma levels of serotonin and urinary excretion of 5-hydroxyindoleaetic acid
447
What drugs can cause carcinoid heart disease
Funfluramine (appetite suppressant) ergot alkaloids, methysergidee, ergotamine therap
448
What is the morphology of carcinoid heart dz
Glistening white intimal plaque like thickening of endocardial surfaces of cardiac chambers and valve leaflets; typical findings are tricuspid insufficieny and pulmonary stenosis
449
What are the types of valvular prostheses
- mechanical valves: consist of different configurations of rigid non physiologic material such as caged balls, tilting disks, or hinged semicircular flaps (bi-leaflet tilting disk valves)
- tissue (bioprostheses): porcine aortic valves or bovine pericardium preserved in glutaraldehyde solution and mounted on prosthetic rare; frozen human valves from deceased onors (homografts)
450
What is the major complication of mechanical valves
Thromboembolism; blood flow through mech valves is non laminar -> stasis and thrombus *need long term anticoagulants
451
Which kind of prosthetic valve carries an increased risk of structural deterioration
Bioprostheses
452
Which kind of valve is affected by infective endocarditis
*either*; in mechanical valves often causes formation of valve abscess
453
What are primary vs secondary cardiomyopathies
Primary: acquired or genetic
secondary: part of a systemic disease
454
Are chronic myocardial dysfunctions resulting from ischemia, valvular abnormalities, or HTN classified as cardiomyopathies
No
455
What are the 3 patterns of cardiomyopathies
- dilated cardiomyopathy (most common) - leads to systolic dysfunction
- hypertrophic cardiomyopathy - leads to diastolic dysfunction
- restrictive cardiomyopathy - leads to diastolic dysfunction
456
What are the causes of dilated cardiomyopathy
Genetic, alcohol, peripartum, myocarditis, hemochromatosis, chronic anemia, doxorubicin toxicity, sarcoidosis, idiopathic
457
What are the causes of hypertrophic cardiomyopathy
Genetic, friedrich ataxia, storage diseases, infants of diabetic mother
458
What are the causes of restrictive cardiomyopathy
Amyloidosis, radiation induced fibrosis, idiopathic
459
What mutations are associated with genetic causes of dilated cardiomyopathy
TTN (Titin); AD is predominant pattern but can be x linked (after puberty - can also be associated with mutation in dystrophin ) AR and mitochondrial (pediatric)
460
What kind of myocarditis causes dilated cardiomyopathy
Viral caused by Coxsackie B
461
Which heavy metal can cause dilated cardiomyopathy
Cobalt
462
What is the primary mechanism that causes pregnancy induced cardiomyopathy
Antiangiogenic mediators produced from prolactin or endothialial growth factor inhibitors as seen with preeclampsia
463
What kind of supraphysiologic stress can cause dilated cardiomyopathy
Excess catecholamines -> myocardial contraction band necrosis (pheochromocytoma, cocaine, or secondary to intracranial lesions or emotional duress), fetus’s of insulin dep diabetic mothers,
464
What is takotsubo cardiomyopathy
Left ventricular contractile dysfunction following extreme physiologic stress -> left ventriclar apex is most affected leading to apical ballooning
465
What proteins are mutation in dilated vs hypertrophic cardiomyopathy
Dilated: sarcoglycan, dystrophin, Desmin, titin, mitochondrial proteins, lamin A/C
Hypertrophic: myosin binding protein C, myosin light chains
Both: troponin I/T, alpha tropomyosin, actin, beta myosin heavy chain
466
What do all of the mutated genes that cause hypertrophic cardiomyopathy encode for
Proteins of the sarcomere *100% genetic
467
How does dilated cardiomyopathy present
Btw 20-50; CHF including dyspnea, easy fatigability, poor exertional capacity; at end stage, ejection friction les than 25%; death from arrhythmia
468
What is arrhythmogenic right ventricular cardiomyopathy
Inherited dz of myocardium causing right ventricular heart failure and rhythm disturbances (particularly v tach or v fib) with sudden death; right ventricular wall is severely thinned due to loss of myocytes accompanied by fatty infiltration an fibrosis *not an inflammatory cardiomyopathy; AD
469
What is Naxos syndrome
Arrhytmogenic right ventricular cardiomyopathy and hyperkeratosis of plantar palmar skin surfaces associated with mutations in gene encoding desmosome associated protein plakoglobin
470
What are the features of hypertrophic cardiomyopathy
Genetic; myocardial hypertrophy, non compliant left ventricular myocardium leading to abnormal diastolic filling and intermittent ventricular outflow obstruction
471
What is asymmetric septal hypertrophy
Ventricular septum thickens more than free wall *banana like configuration; usually most prominent in subaortic region; thickening of anterior mitral leaflet causing systolic anterior motion of the anterior leaflet on echo
472
What are the histo features of hypertrophic cardiomyopathy
Myofiber array intersistial and replacement fibrosis
473
What are the clinical features of hypertrophic cardiomyopathy
Reduced stroke volume; increase in pulmonary venous pressure -> exertional dyspnea; harsh systolic ejection murmur cause by ventricular outflow obstruction as anterior mitral leaflet moves toward ventricular septum; a fib, mural thrombus, ventricular Arrhythmias and sudden death; can treat with beta blockers
474
What are the morph features of restrictive cardiomyopathy
Ventricles ar normal size or slightly enlarged; cavities not dilated; myocardium is firm and non compliant; biatrial dilation;
475
What is endomyocarial fibrosis
Disease of children and young adults in africa and tropical areas; fibrosis of endocardium and subendocardium which diminishes compliant of ventricles
476
What is Loeffler endomyocarditis
Results in endomyocardial fibrosis with large mural thrombi; peripheral eosinophilia in multiple organs -> MBP induces necrosis;; many have a myeloproliferative disorder associated with chromosomal rearrangements involving PDGR genes *treat with imtinib; otherwise rapidly fatal
477
What is endocardial fibroelastosis
Uncommon; fibroelastic thickening of let ventricular endocardium; most common in first 2 year of life; in 1/3 of cases assoc with aortic valve obstruction; can represent a common morph endpoint of dif insults (mumps, mutations in gene for tafazzin- affects mitochondrial membrane)
478
What is myocarditis
Infectious microorganisms or inflammatory process cause myocardial injury
479
What is the most common cause of myocarditis
Viral infections; Coxsackie A and B*; others: HIV, influenza, CMV
480
Which nonviral agents cause myocarditis
T cruzi, trichinlla spiralis (trichinosis), toxoplasmosis, Lyme, diphtheria
481
What are the noninfectious causes of myocarditis
Hypersensitivity or giant cell myocarditis
482
What is the morphology of myocarditis
Heart is normal or dilated; interstitial inflammation (primarily lymphocytic) and focal necrosis
483
What is the morphology of hypersensitivity myocarditis
Interstitial infiltrates with eosinophils
484
What is the prognosis of giant cell myocarditis
Poor
485
Which drugs cause hypersensitivity myocarditis
Methyldopa an sulfonamides
486
Which drugs cause myocardial disease
Doxorubicin and daunorubiin -> cause peroxidation of lipids in myocyte membranes; lithium, phenothiazines, chloroquine
*cause myofiber swelling, cytoplasmic vacuolization and fatty change
487
What can case amyloid deposits in the heart
Systemic amyloidosis (myeloma) or senile cardiac amyloidosis (better prognosis than systemic)
488
What are senile cardiac amyloid deposits composed of
Transthyretin (sythesized in liver and transports thyroxine and retinol binding protein) *4% of AA have transthyretin mutation that substitutes isoleucine for valine at pos 122 that is responsible for AD familial transthyretin amyloidosis
489
What kind of cardiomyopathy does cardiac amyloidosis produce
Restrictive
490
What is the morphology of cardiac amyloidosis
Heart is either normal or firm and rubbery; chambers usually of normal size; semi translucent nodules resembling drips of wax can be an on atrial endocardial surface; hyaline deposits of amyloid
491
What color is the fluid that is normally in the pericardial sac
Straw colored
492
What kind of pathological fluid can be found in the pericardial sac
Serous (effusion), blood (hemopericradium), pus (purulent pericarditis)
493
What causes primary pericarditis
Highly unusual but from viral infections
494
What are causes of serous pericarditis
Rheumatic Fever, SLE, scleroderma, tumors (lymphatic invasion) and uremia; infection of tissues near pericardium can cause irritation and a sterile serous effusion that can progress to serofibrinous pericarditis and a suppurative reaction
495
What are the most frequent types of pericarditis
Fibrinous and serofibrinous; common causes are acute MI, postinfarction dressler syndrome, uremia, chest radiation, RF, SLE, trauma, cardiac surgery
496
What is the morphology of fibrinous and serofibrinous pericarditis
Surface is dry with fine granular roughening; serofibrinous is more intense inflammatory process -> induces accumulation of larger amounts of yellow to brown turbid fluid containing white cells, red cells, and fibrin
497
What are the sx of fibrinous pericarditis
Pain *position dependent; fever; *loud pericardial friction rub
498
What can cause purulent or suppurative pericarditis
- direct extension from neighboring infection (empyema of pleural cavity, lobar pneumonia, mediastinal infection, ing abscess through myocardium)
- seeding infection from blood
- lymphatic extension
- direct introduction from cardiotomyy
499
What do the serosal surfaces of purulent pericarditis look like
Red granular and coated with equate; can cause mediastinoperiarditis; scarring is usual outcome (constrictive pericarditis)
500
What is the most common cause of hemorrhagic pericarditis
Met malignancy; also seen in bacterial infections and TB
501
What causes caseous pericarditis
Extension of TB from tracheobronchil nodes
502
What are the clinical features of adhesive mediastinopericarditis
Systolic retraction of rib cage and diaphragm, pulses paradoxus
503
What is concretio cordis
Plaster mold scar (calcified pericarditis)
504
What are signs of constrictive pericarditis
Muffled heart sounds, elevated jugular venous pressure, peripheral edema; Need perricardiectomy (Removal of fibrous tissue)
505
What is the most common heart finding in rheumatoid arthritis
Fibrinous pericarditis; also can cause rheumatoid valvulitis of aortic valve cusps
506
What are the most common primary cardiac tumors
Myxomas, fibromas, lipomas, papillary fibroelstomas, rhabdomyomas, angiosarcomas - first 5 are all benign
507
What are the familial syndromes associated with myxomas of the heart
Activating mutations in GNAS1 gene (encodes subunit of G protein) - McCune Albright syndrome; or null mutations in PRKAR1A (nodes cAMP dependent protein K) - carney complex; most arise in left atria
508
What is the morphology of myxomas of the heart
Usually single; region of fossa ovalis in atrial septum is favored; can cause AV valve obstruction or cause damage to leaflets (wrecking ball effect); histo: stellate or glomerular myxoma cells in mucopolysaccharide ground substance; vessel like and gland structures are characteristic usually has hemorrhage and mononuclear inflammation
509
What are the indirect thrombin and factor Xa inhibitors
- unfrationated heparin (heparin sodium)
- low molecular weight heparin (enoxaparin, tinzaparin, dalteparin)
- synthetic pentasaccharide (fondaparinux)
510
What are the direct thrombin inhibitors
Lepirudin, bivalirudin, argatroban
511
What a re the oral anticoagulants
- coumarin anticoagulants (warfarin)
- direct oral anticoagulants (factor Xa inhibitors -rivaroxabn, apixaban, edoxaban; direct thrombin inhibitor - dabigatran)
512
What are the antiplatelet drugs
- inhibitors of thromboxane A2 synthesis: aspirin
- ADP receptor blockers: clopidogrel, prsugrel, ticlopidine, ticagrelor
- plt glycoproteins receptor blockers: abciximab, epitifibatide, tirofiban
- inhibitors of phosphodisterases: dipyridamole, cilostazol
513
What are the thrombolytic drugs
- tissue type plasminogen activator drugs:: alteplase, reteplase, tenecteplase
- urokinase-type plasminogen activator: urokinase
- streptokinase preparations streptokinase
514
What is a white thrombus
Platelet rich; forms in high pressure aa
515
What is a red thrombus
Fibrin rich with trapped RBCs; forms in veins and heart
516
Which kind of clots are anticoagulants used to prevent
Red clots
517
Which clots are antiplatelet drugs used to prevent
White clots
518
What is the MOA of indirect thrombin and FXa inhibitors
Bind serine protease inhibitor antithrombin III and increases its activity - inhibits thrombin (IIa), IXa and Xa
519
What is the difference in the MOA between HMW heparin, LMW heparin, and fondaprinux
- HMW inhibits thrombin and factor Xa
- LMW inhibits factor Xa with little effect on thrombin
- fondaparinux inhibits factor Xa with no effect on thrombin
520
How must heparin be administered
IV or SC; LMW requires less frequent injections
521
What is heparin used for
Treats disorders secondary to red thrombi to reduce risk of emboli; administer to ppl with atrial Arrhythmias, DVT, prevention of emboli during surgery or in hospitalized patients; heparin lock prevents clots from forming in catheters
522
How do you monitor patients on heparin
Monitor activated partial thromboplasin time; measures intrinsic pathway (phospholipids, an calcium mixed with patients plasma); evaluates II, IX, X, XI, XII); anti-Xa assay
523
What side effects should you look for in patients on heparin
Heparin induced thrombocytopenia (thrombosis and thrombocytopenia)
524
What are the contraindications to heparin
Severe HTN, active tuberculosis, ulcers of GI tract, patients with recent surgeries
525
What is administered to reverse heparin action
Protamine sulfate
526
What are the indications for fondaprinux
Prevention of DVT, treatment of acute DVT in conjunction with warfarin, treatment of PE
527
What is the MOA of the direct thrombin inhibitors
- bivalent direct thrombin inhibitors (bind at both active site and substrate recognition site): lepirudin, bivalirudin
- inhibitors binding only at thrombin active site: argatroban
528
What is the difference between lepirudin and bivalirudin
Lepirudin is a inrreversible inhibitor of thrombin; bivalirudin is a reversible inhibitor of thrombin (also inhibits platelet aggregation)
529
What are the feature of argatroban
Small molecular weight inhibitor; short acting; use IV
530
What are the indications for direct thrombin inhibitors
HIT, coronary angioplasty (bivalirudin and argatroban)
531
What are the adverse effects of direct thrombin inhibitors
Bleeding (no antidote), repeated lepirudin use can cause anaphylactic reaction
532
What is the MOA of warfarin
Inhibits reactivation of vitamin K by inhibiting vit K epoxied reductase; inhibits carboxlation of glutamate residues by glutamyl carboxylase in prothrombin an factors VII, IX, and X making them inactive
533
Which proteins are affected by the carboxylation that is inhibited by warfarin
Factor II, VII, IX, and X; bone ossification and ECM formation
534
What are the pharmacokinetics of warfarin
2 isomers: R and S; S is more potent; R metabolized by CYP3A4; S metabolized by CYPC9; pumped out of hepatocytes by ABCB1 transporter and excreted in bile
535
How is warfarin administered
Orally; 100% bioavailability ; delayed onset of action (12h) long half life;; most is bound in plasma albumin
536
What are the clinical uses of warfarin
Prevent thrombosis or prevent/treat thromboembolism, a fib, prothestic heart valves
537
What are the adverse effects of warfarin
Teratogenic (bleeding disorder in fetus and abnormal bone formation), skin necrosis, infarction of breasts, intestines or extremities, osteoporosis, bleeding
538
How is warfarin dose titration
```
Prothrombin time (extrinsic pathway - ad tissue factor)
-INR: .0-1.3 is normal, .5 high change of thrombosis, 4-5 high chance of bleeding, 2-3 range for patients on warfarin
```
539
What population is more resistant to warfarin
AA b/c have a high dose haplotype of vit K epoxied reductase complex; Asian Americans less resistant because have low dose haplotype
540
What disease states interact with warfarin
Hepatic disease and hyperthyroidism (both increase prothrombin Time)
541
Which drugs interact with warfarin by increasing prothrombin time
- pharmacokinetic: amiodarone, cimetidine, disulfiram, metronidazole, fluconazole, phenylbutazone, sulfinpyrazone, trimethoprim-sulfamethoxazole
- pharmacodynamic: aspirin, cephalosporins (3rd gen) heparin
542
Which drugs interact with warfarin by decreasing prothrombin time
- pharmacokinetics: barbiturates, cholestyramine, rifampin
| - pharmacodynamic: diuretics, vitamin K (also hypothyroidism)
543
What are the advantages and drawbacks of warfarin
Advantages: oral, long duration of action, drug clearance is independent of renal function, can be reversed with vit K administration or frozen plasma or prothrombin complex
Drawbacks:dosing variability which can lead to bleeding complications, requires INR monitoring
544
What are the factor Xa inhibitors used for
(Rivaroxaban, apixaban, edoxaban) prevention of thromboembolism, treatment of thromboembolism, prevention of stroke in patients with a fib
545
What are the advantages vs drawbacks of factor Xa inhibitors
Advantages: oral, fixed doses, does not require monitoring, rapid onset of action as compared to warfarin
Drawbacks: excreted by kidneys, dose adjustment needed in renal patients
546
What is the clinical use of dabigatran
Reduce risk of stroke and systemic embolism in patients with non-valvular a fib; treatment of venous thromboembolism
547
What are the advantages and disadvantages of dabigatran
Advantages: predictable pharmacokinetics, fixed dosing and no monitoring, rapid onset and offset, no interaction with CYP50, antidote (idarucizumab)
Disadvntge: renal excretion
548
What is the antidote for DOAC FXa inhibitors
Andexanet alpha
549
Which monitoring tests are done for each of the anticoagulants
Heparin: aPTT, anti-Xa
Warfarin: PT INR
DOAC-FXa inhibitors: anti-Xa
DOAC DTI: diluted thrombin time (TT)
550
What is the clinical use for. Aspirin as an anti platelet
Primary and secondary prevention of heart attack, stroke, arterial thrombosis of limbs
551
What are the adverse effects of aspirin
Peptic ulcer, GI bleeed
552
What is the MOA of the ADP receptor blockers
Relieves the inhibition of AC by alpha i -> increases production of cAMP
553
What is the function of the inhibitors of phosphoiesterase inhibitors in antiplatelet drugs
Inhibition of cAMP degredation
554
What are the Pharmacogenomics of clopidogrel
Metabolized by CYP2C19 which is nonfunctional in half of Chinese, some AA, Caucasian’s and Mexican Americans
555
What do platelet GP receptor antagonists target
arg-gly-asp sequence; prevent binding of ligands to GP IIb/IIIa receptor to inhibit platelet aggregation
556
What are the clinical uses of antiplatelet drugs
Prevention of thrombosis in unstable angina, prevention of ischemic stroke and arterial thrombosis in PVD, patients undergoing coronary a angioplasty and stenting, *inhibitors of phosphodiesterase used in combo with other antiplatelet agents
557
What are inhibitors of phosphodiesterase used in combo with
- dipyridamole with aspirin to prevent CVA
- dipyridamole with warfarin in patients with prosthetic heart valves
- cilostazol for claudication
558
How do fibrinolytic drugs work
Activate endogenous fibrinolytic system by converting plasminogen to plasmin
559
What does tPA need as a coactivator
Fibrin
560
Where is urokinase type plasminogen produced
Kidneys
561
How does streptokinase work
Converts plasminogen to plasmin non-proteolytically
562
What are the thrombolytic drugs used for
Acute embolic/thrombotic stroke (within 3h), acute MI (within 3 -6h), PE, DVT ascending thrombophlebitis
563
Which fibrinolytic drug has allergic reactions
Streptokinase
564
What adverse effects do both streptokinase and urokinase have
Bleeding from systemic fibrinogenolysis because they are nonfibrin specific plasminogen activators
565
What are the clinical manifestations of myxomas
Due to valvular ball valve obstruction, embolization or syndrome of constitutional sx (due to elaboration of IL-6); use echo to dx tx with surgery
566
What are lipomas
Occur in subendocardium, subepicrdiumm or myocardium; can produce ball valve obstruction or Arrhythmias; most often in left ventricle, right atrium, or atrial septum (cause lipomatous hypertrophy)
567
What are papillary fibroelastomas
Usually incidental sea anemone like lesions; May embolic; usually located on valves on semilunar and atrial surfaces of AV valves; cluster of hair like projections
568
What are rhabdomyomas
Most frequent primary tumor of pediatric heart; commonly discovered because off obstruction of a valvular orifice or cardiac chamber; involve ventricles; *spider cells half are assoc with tuberous sclerosis *regress spontaneously
569
What are the most frequent metastatic tumors of the heart
Carcinomas of the lung and breast, melanomas, Leukemias and lymphomas; most carcinomas spread by lymphatics
570
What cancers can cause superior vena cava syndrome
Bronchogenic carcinoma or malignant lymphoma
571
How does renal cell carcinoma spread to the heart
Via IVC
572
How do you diagnose acute cardiac rejection of a transplanted heart
Endomyocardial biopsy
573
What is cellular rejection
Interstitial lymphocytic inflammation with myocyte damage; histo resembles myocarditis
574
What is the most important long term limitation for cardiac transplantation
Allograft arteriopathy - progressive diffusely. Stenosising intimal proliferation in coronary aa
575
What can transplanted hearts not get
Angina
