Goljy 10: Vascular Disorders Flashcards
1
Q
Chylomicrons
A
- Transport diet-derived triglycerides in the blood
- Absent during fasting
2
Q
Composition of chylomicrons
A
2% Protein
87% triglyceride
3% cholesterol
8% phospholipid
The least dense of all lipoproteins!
3
Q
How are chylomicrons formed in the small intestine?
A
- Enterocytes lining villi reabsorb monoglycerides and fatty acids, which are converted to TG in cytosol
- TG packaged into a chylomicron, requiring apoB48 for assembly and secretion
- Nascent chylomicrons enter lymphatics that drain into thoracic duct, emptying into blood stream
4
Q
Describe the circulation phase of chylomicrons
A
- Nascent chylomicrons obtain apoCII and apoE from HDL to become mature chylomicrons
- TG in chylomicrons is hydrolyzed by capillary lipoprotein lipase into FAs + glycerol
- Hydrolysis of chlyomicrons by CPL leaves chylomicron remnants that contain much less TG than mature chylomicrons
- Chylomicron remnants removed from circulation by apoE receptors in liver
5
Q
VLDL
A
- TG in the liver is synthesized by adding 3 FAs to glycerol-3-phosphate (G3P is a 3-carbon intermediate of glucose metabolism)
- With the aid of apoB100, TG is packaged into VLDL and secreted into blood as nascent VLDL
6
Q
Composition of VLDL
A
9% Protein
55% TG
17% Cholesterol
19% Phospholipid
7
Q
What is VLDL a source of?
A
FAs and glycerol!
- TG in VLDL is hydrolyzed by CPL into FAs and glycerol
- Hydrolysis of nascent VLDL by CPL first produces IDL further hydrolysis produces LDL
- Some IDL is removed from blood by apoE receptors in liver
8
Q
Cholesterol ester transport protein
A
- Transfers CH from HDL to VLDL and TG from VLDL to HDL
- interferes with HDL’s main function of transferring CH from peripheral tissue to liver for excretion in bile or synthesis of bile salts/acids - Increase in VLDL always causes decrease in HDL-CH (explains why increased VLDL is risk for CAD)
9
Q
VLDL concentration formula
A
VLDL = TG/5
10
Q
Clinically important serum TG levels
A
Optimal: 500
11
Q
Causes of increased plasma turbidity
A
d/t very high levels of TGs in serum (usually >1000)
If milky material is on TOP of tube –> increased chylomicrons
- MCC is that person did not fast before lipid study, otherwise they have type I hyperlipoproteinemia
If milky material is dispersed throughout plasma –> VLDL increased
- Type IV hyperlipoproteinemia
If supranate and infranate present, then chylomicrons AND VLDL increased
- Type V hyperlipoproteinemia
12
Q
LDL
A
- Transports CH in the blood
- Derives from continued hydrolysis of IDL by CPL
- Removed from blood by LDL receptors in peripheral tissue
- Small, dense LDL particles, a/w increased risk of atherosclerosis and CAD
- Increased in diets that are high carb
13
Q
Composition of LDL
A
22% protein
10% TG
47% cholesterol
21% phospholipid
14
Q
Why is fasting not required for an accurate serum CH?
A
CH content in chylomicrons is
15
Q
Risk factors for CHD
A
- Age (>45 males, >55 females)
- Family history of premature CHD
- LDL >160
- Current smoker
- BP >140/90 or on antihypertensive meds
- HDL
16
Q
HDL
A
- “good cholesterol”
- can be increased by nicotinic acid (best) and exercise
- diet alterations are not effective
- synthesized by liver and small intestine
17
Q
HDL composition
A
50% protein
3% TG
20% CH
27% Phospholipid
18
Q
Functions of HDL
A
- Source of apoE, apoCII for other lipoprotein fractions
- Removes CH from fatty streaks and atherosclerotic plaques (HDL delivers CH from peripheral tissue to liver –> excreted in bile or converted into bile acid/salt)
19
Q
Lab measurement of HDL
A
- reported as HDL-CH
- increased HDL-CH –> decreased risk for CHD
- decreased HDL-CH if VLDL increased
- high (optimal) is >60, low (suboptimal) is
20
Q
Type 1 hyperlipoproteinemia
A
aka familial chylomicronemia
- AR, childhood disease
- deficiency of CPL or apoCII
- Chylomicrons increased in early childhood, VLDL increases later in life
- Presents w/ acute pancreatitis
- LABS: increase in serum TG (>1000) –> turbid supranate, clear infranate. Normal to moderately increased serum CH.
21
Q
Type 2 hyperlipoproteinemia
A
Type IIa: increase in serum CH (>260) and LDL (>190), serum TG (260) and LDL (>190), serum TG (>300)
22
Q
Causes of acquired cases of type II hyperlipoproteinemia
A
- Primary hypothyroidism: decreased synthesis of LDL receptors
- Blockage of bile flow: bile contains CH
- Nephrotic syndrome: increased liver synthesis of CH
23
Q
Polygenic hypercholesterolemia
A
- Type IIa hyperlipoproteinemia
- MC type
- Multifactorial inheritance
- Alteration in regulation of LDL levels with primary increase in serum LDL and TG
24
Q
Familial combined hypercholesterolemia
A
- Type IIb hyperlipoproteinemia
- AD inheritance
- CH and TG begin to increase around puberty. A/w metabolic syndrome. Increase in CH and TG >300. Decrease in HDL.
25
Familial hypercholesterolemia
- Type IIa hyperlipoproteinemia
- AD inheritance
- Deficiency of LDL receptors
- Achilles tendon xanthoma, xanthelasma. Premature CAD and stroke. Increase in serum CH and LDL. Serum TG
26
Type III hyperlipoproteinemia
- Familial dysbetalipoproteinemia or "remnant disease"
- AR inheritance
- Deficiency of apoE. Decreased liver uptake of IDL and chylomicron remnants.
- Palmar xanthomas in flexor creases. Increased risk for CAD and peripheral vascular disease.
- Both serum CH and TG >300. LDL
27
Acquired causes of type IV hyperlipoproteinemia
- Excess alcohol intake: MCC --> increased production of VLDL, decreased activity of CPL
- Oral contraceptives: estrogen increases VLDL synthesis
- Diabetes: decreased adipose and muscle CPL (decreased VLDL clearance; decreased insulin responsible for decreased synthesis of CPL). Increased LDL, decreased HDL.
- Chronic renal failure: increased synthesis of VLDL and decreased clearance of VLDL.
- Thiazide diuretics, B-Blockers: inhibition of CPL (decreases clearance of VLDL)
28
Familial hypertriglyceridemia
- MC hyperlipoproteinemia
- Increasd production of VLDL, decreased clearance of VLDL
- Increased risk for CAD and peripheral vascular disease
- Eruptive xanthomas
- Increase in TG (>300). Serum CH normal to moderately increased (250-500). Serum LDL
29
Type V hyperlipoproteinemia
- Most commonly familial hypertriglyceridemia + an exacerbating disorder
- increase in chylomicrons and VLDL d/t decreased activation and release of CPL
- Hyperchylomicronemia syndrome
- Eruptive xanthomas, increased acute pancreatitis, lipemia retinalis, dyspnea and hypoxemia, hepatosplenomegaly, increase in serum TG (>1000). Normal serum CH and LDL.
- Turbid supranate and infranate
30
Nonpharmacologic tx of type II hyperlipoproteinemia
- Dietary modification (low fat)
- Increasing activity, aerobic exercise
- Smoking cessation
31
Pharmacologic tx of type II hyperlipoproteinemia
- HMG-CoA reductase inhibitors ("statins")
- nicotinic acid
- bile salt sequestrants
- cholesterol absorption inhibitors
32
Nonpharmacologic tx of type IV hyperlipoproteinemia
- Reduce alcohol intake
- Reduce carbohydrate intake
- Increase intake of omega3 fatty acids
33
Pharmacologic tx of type IV hyperlipoproteinemia
Nicotinic acid or fibric acid derivatives
34
Arteriosclerosis
Thickening and loss of elasticity of arterial walls
35
Medial calcification
- dystrophic calcifications in the wall of muscular arteries
- can be seen in plain radiographs
- no clinical consequence UNLESS a/w atherosclerosis
36
Atherosclerosis epidemiology
- MC in men
- Increases w/ age
RISKS:
- HTN (accelerates by producing endothelial cell dysfunction)
- DM (a/w hyperlipidemia and HTN which are risk factors, also a/w abnormalities of coagulation, platelet adhesion and aggregation, increased oxidative stress, fxnal changes in endothelium)
- Cigs, hyperlipoproteinemias, previous Chlamydophilia pneumoniae infxn
37
Pathogenesis of atherosclerosis
- D/t endothelial cell damage of muscular and elastic arteries
- Veins under increased pressure undergo atherosclerosis
38
Causes of endothelial cell injury
Stress areas in the vasculature (eg. bifurcation), HTN, tobacco, homocysteine, oxidized LDL, small dense LDL
39
Cell response to endothelial injury
1. Macrophages infiltrate the intima, platelets adhere to damaged endothelium
- platelets produce inflammatory response in leukocytes and endothelial cells
- Platelet-mediated inflammatory response occurs even with platelet-inhibiting drugs
2. Inflammatory cells release cytokines and growth factors --> hyperplasia of smooth muscle cells (SMCs)
3. SMCs migrate to tunica intima
4. CH enters SMCs and macrophages, producing foam cells
5. SMCs and macrophages release cytokines that produce extracellular matrix (collagen, proteoglycans, elastin)
40
Development of a fibrous plaque
- Components: SMCs, foam cells, inflammatory cells, ECM
- Overlies a necrotic center containing cellular debris, CH crystals, foam cells
- Disrupted plaques may extrude underlying necrotic material, which extends to the endothelial surface serving as a nidus for thrombus formation
- Frequently becomes dystrophically calcified and ulcerated
41
MC sites of atherosclerosis
Descending order: abdominal aorta, coronary artery, popliteal artery, internal carotid artery
42
Serum C-reactice peptide
Increased in patients with disrupted plaques.
Plaques may rupture and produce vessel thrombosis --> acute MI
CRP may be stronger predictor of cardiovascular events than LDL
43
Complications of atherosclerosis
- Vessel weakness
- Vessel thrombosis
- Hypertension
- Cerebral atrophy
- PAD
44
Peripheral arterial disease epidemiology
- Increases w/ age, equal in men and women
| - Blacks > whites
45
Peripheral arterial disease sx
1. Claudication - pain, weakness, numbness, cramping d/t decreased arterial blood flow
2. Sores, wounds, ulcers --> gangrene
3. Dependent rubor of feet
4. Cool skin temp
5. Diminished hair and nail growth on limb digits
6. Diminished pedal pulses, bruits over femoral/popliteal arteries
46
5 P's of acute PAD occlusion
Pain, Pallor, Paresthesias, Paralysis, Pulselessness below occlusion
47
Diagnosis of PAD
- Measure ABI (ratio
48
Tx of PAD
- Manage risk factors
- Revascularization surgical procedures
- Cilostazol
49
Arteriolosclerosis
- Hardening of the arterioles
| - Two types: hyaline and hyperplastic
50
Hyaline arteriolosclerosis
- Increased protein is deposited in vessel wall, occludes lumen
51
Causes of hyaline arteriolosclerosis
DM:
- Glucose combines w/ proteins in basement membrane of arterioles = nonenzymatic glycosylation (NEG)
- NEG causes basement membrane to leak proteins from plasma into vessel wall
HTN:
- increased intraluminal pressure pushes plasma proteins into vessel wall
52
Hyperplastic arteriolosclerosis
- Acute increase in BP causes basement membrane duplication and smooth muscle hyperplasia in renal arterioles
- Renal arterioles have "onion skin" appearance
53
Aneurysm
Weakening of the vessel wall, followed by dilation d/t increased wall stress
54
Abdominal aortic aneurysm epidemiology
- MC aneurysm
- Usually in men >60
- Usually located below the renal artery orifices
55
AAA pathogenesis
Atherosclerosis weakens the vessel wall
- Vessel wall stress increases with vessel diameter
- Vessel lumen fills with atheromatous debris and blood clots
Other factors: familial, structural defects in connective tissue, absence of vasa vasorum in abdominal aorta
56
Clinical findings in AAA
- Usually asymptomatic
- Pulsatile epigastric mass that may or may not be tender
- Bruit heard if renal artery stenosis or visceral arterial stenosis is present
- Atherosclerotic plaques can chip off and embolize to distal extremities
- Rupture is MC complication
57
Rupture triad in AAA
1. Sudden onset severe left flank pain (bleed is initially retroperitoneal) followed by
2. hypotension from blood loss into retroperitoneum
3. presence of pulsatile mass on exam
58
Greatest predictor for AAA rupture
Diameter of aneurysm
| - surgical repair beneficial for AAAs 5.0-5.4 cm in diameter
59
Dx, Tx of AAA
Dx: Ultrasound is 100% accurate, CT used pre-op to localize extent into renal vessels and evaluate vessel wall integrity to exclude rupture, angiography give detailed arterial anatomy
Tx: Endovascular or open surgery
60
Popliteal artery aneurysm
1. 95% of cases are males
2. MC peripheral artery aneurysm
3. Pulsatile mass behind the knee
4. Treated surgically
61
Mycotic aneurysm
- Vessel wall weakens d/t infection
- Fungal invaders: Aspergillus, Candida, Mucor
- Bacterial invaders: Bacteroides fragilis, Pseudomonas aeruginosa, Salmonella
62
Clinical findings, tx for mycotic aneurysm
Clinical findings:
- thrombosis w/ or w/o infarction
- rupture
Tx: surgical
63
Berry aneurysm
Saccular dilatation typically found around the circle of Willis and base of the brain, MC site is junction of communicating branches w/ ACA
64
Risk factors for berry aneurysm
- Normal hemodynamic stress
- Presence of HTN
- Coarctation of aorta
- Atherosclerosis
65
Pathogenesis of berry aneurysm
- At the junction of the communicating branches w/ main cerebral vessels, the vessel lacks an internal elastic lamina and smooth muscle
- Rupture of the aneurysm releases blood into the subarachnoid space or into the brain parenchyma
66
Clinical findings of berry aneurysm
- Sudden onset of severe occipital headache, "worst headache I've ever had"
- Nuchal rigidity from meningeal irritation
67
Complications of ruptured berry aneurysm
- Death shortly after bleed
| - Rebleeding, hydrocephalus, neurologic deficits
68
Dx, Tx of ruptured berry aneurysm
Dx: CT scan and angiography
Tx: immediate surgical repair
69
Syphilitic aneurysm
- Complication of tertiary syphilis d/t Treponema pallidum
| - Usually men 40-55 years of age
70
Pathogenesis of syphilitic aneurysm
1. T pallipum infects vasa vasorum of the ascending and transverse portions of aortic arch
- vasculitis is called endarteritis obliterans
- characteristic plasma cell infiltrate in vessel wall
- inflammation is intense and often occludes lumen of vessel
2. vessel ischemia of the medial tissue leads to weakness and subsequent dilation of the aorta and aortic valve ring
71
Clinical findings of syphilitic aneurysm
- AV regurgitation
| - Brassy cough (L recurrent laryngeal nerve stretched by aneurysm)
72
AV regurgitation
- problem in closing AV
- AV closes in diastole, so murmur occurs in early diastole as blood leaks back into ventricle
- increase in LV end-diastolic volume --> increase in stroke volume (increased systolic pressure)
- Blood rapidly draining back into LV decreases diastolic pressure
- Wide pulse pressure --> bounding pulses
-
73
Austin Flint murmur
Excessive blood drips back onto MC leaflet, producing diastolic murmur
- indicates need for aortic valve replacement
74
Dx and Tx of syphilitic aneurysm
Dx: linear calcifications seen in aortic wall on plain radiograph, aortography is definitive dx
Tx: abx for tertiary syphilis and surgery if warranted
75
Aortic dissection epidemiology
- MC in men w/ mean age of 40-60, hx of HTN
| - Commonly occurs in young people with connective tissue disorder (Marfan syndrome or Ehlers-Danlos)
76
Aortic dissection pathogenesis
Cystic medial degeneration (CMD): elastic tissue fragmentation in media weakens the elastic artery. Degraded matrix material collects in areas of fragmentation in media.
77
Risk factors for CMD
1. Increased wall stress from: HTN, pregnancy, coarctation of aorta
2. Defects in connective tissue: Marfans (defect in elastic tissue), EDS (defect in collagen)
78
Marfan syndrome
- AD
- Results in production of weak elastic tissue d/t missense mutation in synthesis of fibrillin
- Cardiovascular abnormalities
- Dilation of ascending aorta --> aortic dissection/AV regurg
- Mitral valve prolapse is MC valvular defect, often a/w conduction defects
- Skeletal defects: hypermobile joints, eunuchoid proportions, arachnodactyly
- Dislocation of lens
79
Intimal tear in aorta
- D/t HTN or underlying structural weakness in media
- Usually occurs within 10 cm of AV
- Blood dissects under arterial pressure through areas of weakness
- Blood dissects proximally and or distally
80
Clinical findings in aortic dissection
1. Acute onset of severe retrosternal chest pain radiating to the back
2. AV regurgitation d/t AV ring dilation
- radiograph or echocardiogram shows widening of AV root
- axial CT shows true and false lumen of dissection
3. Loss of upper extremity pulse (compression of subclavian artery by blood in false lumen)
4. Rupture sites: pericardial sac MC, pleural cavity, peritoneal cavity
81
Saphenous venous system
- Superficial saphenous veins drain blood into deep veins via perforating branches
- Valves in perforator branches prevent reversal of blood flow into superficial system
- Deep veins direct blood back into heart
82
Varicose veins
Veins that are abnormally distended (>3 mm) and often tortuous underneath the skin surface
83
Locations of varicose veins
1. Superficial saphenous veins (MC)
2. Distal esophagus (d/t portal HTN)
3. Anorectal region (internal hemorrhoids)
4. Left scrotal sac
84
Superficial varicosities in the lower extremities
- MC clinical manifestation of chronic venous insufficiency
| - Risk factors: female, FH, multiple pregnancies, jobs with prolonged standing, obesity, advanced age
85
Pathogenesis of superficial varicosities in LE
1. Valve incompetence of perforator branches with reversal of blood flow from high pressure deep venous system into superficial system
2. May be secondary to DVT
- retrograde blood flow through perforating branches into superficial system causes increased pressure and dilation of vessels
86
Tx of superficial varicosities in LE
Non pharmacologic: Graded compression stockings
| Chronic tx: compression sclerotherapy, ligation and stripping, endovenous obliteration using radiofrequency or laser
87
Causes of venous thromboses
- Stasis of blood flow (prolonged immobilization, post-ob)
- Hypercoagulability (antithrombin III deficiency, oral contraceptives, pancreatic cancer, factor V deficiency, protein C and S deficiencies)
88
Locations of venous thromboses
1. MC in deep veins of lower extremity: anterior, posterior, peroneal veins in calf, popliteal/femoral veins
2. Less common: periprostatic plexus, ovarian and periuterine veins, portal vein, hepatic vein, dural sinuses in brain
89
DVT in calf acute sx
1. Swelling of affected leg
2. Pain on dorsiflexion of foot (Homans sign) and compression of calf
3. Pitting edema distal to thrombosis d/t increased hydrostatic pressure
90
DVT in calf chronic sx
1. Stasis dermatitis
| 2. Secondary varicosities in superficial system
91
Stasis dermatitis
- Hemorrhagic or orange discoloration of the skin and ischemic ulcers located around the medial malleolus of the ankles
- Orange d/t hemosiderin deposited in skin from ruptured vessels
- Caused by rupture of perforating branches d/t pressure backup from chronic deep vein insufficiency
- Tx: topical high potency corticosteroids and abx if infxn present
92
Dx, Tx of DVT
Dx: Venous duplex ultrasonogaphy + serum D-dimer assay
Tx: low molecular weight heparin, compression stockings, long term treatment to prevent recurrent DVT (warfarin)
93
Superficial thrombophlebitis
- 10-20% a/w occult DVT
CAUSES:
- IV vannulation of veins, MC in plastic catheters inserted into lower extremity veins
- Infection (usually staph aureus)
- Carcinoma of pancreatic head (produces superficial migratory thrombophlebitis = Trousseau sign, d/t release of procoagulants by the cancer)
- Hypercoagulable state
94
Clinical findings in superficial thrombophlebitis
- Pain and tenderness along course of superficial vein
| - Erythema and edema of overlying skin and subcutaneous tissue
95
Tx of superficial thrombophlebitis
- Warm, most compresses
| - NSAIDs, dicloxacillin, cephalexin
96
SVC syndrome
- Extrinsic compression of SVC d/t primary lung cancer
- MCC is small cell carcinoma of lung
- Clinical findings: "puffiness" and blue/purple discoloration of face, arms, and shoulders, retinal hemorrhage, stroke
- Tx: radiation, stent to bypass the obstruction
97
Thoracid outlet syndrome
- Compression of the neurovascular compartment in the neck
- Causes: cervical rib, spastic anterior scalene muscles, positional change in neck and arms in muscular individuals
- Clinical findings: vascular signs like arm falling asleep when person sleeps, nerve root signs (numbness, paresthesias), Positive Adson test
- Tx: manipulation therapy, home exercise, surgery if anatomic cause
98
Adson test
Pulse disappears/diminished when arm is outstretched and patient looks to outstretched arm
99
Structure of lymphatic vessels
Incomplete basement membranes, which predisposes them to infxn and tumor invasion
100
Acute lymphangitis
- Inflammation of lymphatics ("red streak")
- Cellulitis MC caused by strep pyogenes
- Tx: clindamycin/erythromycin
101
Nodular lymphangitis
- Sporotrichosis
102
Lymphedema
- Collection of lymphatic fluid in interstitial tissue or body cavities
- In US, MCC is post-radical mastectomy followed by irradiation of axilla
- Other causes: filariasis (MCC in world), congenital, Turner syndrome
103
Clinical findings in lymphedema
- Early in interstitial edema, there is pitting with compression; in advanced cases it is nonpitting d/t increased fibrosis
- Usually painless and progressive
104
Tx of lymphedema
Complex decongestive therapy including extremity elevation, limb massage, and pneumatic compression
105
Chylous effusions
- Contain chylomicrons and TG
| - In thoracic cavity, caused by damage to thoracic duct by malignant lymphoma or trauma
106
Vasculitis
Inflammation of small vessels (arterioles, venules, capillaries), medium-sized vessels (muscular arteries), large vessels (elastic arteries), or a combination of these vessel types
107
Pathogenesis of vasculitis
1. Type III hypersensitivity (immunocomplex, eg. Henoch-Schonlein purpura)
2. Type II hypersensitivity (antigen-antibody, eg. Goodpasture syndrome)
3. ANCA
4. Direct invasion by all classes of microbial pathogens
108
ANCA
- antibodies activate neutrophils, causing release of their enzymes and free radicals, resulting in vessel damage
- c-ANCA type of vasculitis: Ab directed against proteinase 3 in cytoplasmic granules, ex. Wegener granulomatosis
- p-ANCA type of vasculitis: Ab directed against myeloperoxidase in neutrophils, ex. microscopic polyangiitis, Churg-Strauss syndrome
109
Angiomyolipoma
Kidney hamartoma composed of blood vessels, muscle, and mature adipose tissue
- a/w tuberous sclerosis
110
Angiosarcoma
Liver angiosarcoma a/w exposure to polyvinyl chloride, arsenic, or thorium dioxide
111
Bacillary angiomatosis
- Benign capillary proliferation involving skin and visceral organs in AIDS patients
- simulates Kaposi sarcoma in AIDS
- caused by Bartonella henselae, a gram - bacillus
112
Capillary hemangioma
- Facial lesion in newborns, normally regress with age
113
Cavernous hemangioma
MC benign tumor of the liver and spleen
| May rupture if large and produce hemoperitoneum
114
Cystic hygroma
Lymphatic cyst in the neck that may be a/w Turner syndrome
115
Glomus tumor
Painful red subungual nodule in a digit
| Derive from arteriovenous shunts in glomus bodies
116
Hereditary telangiectasia
- Dilated vessels on the skni and mucous membranes in the mouth and throughout the GI tract
- Chronic iron deficiency anemia may occur d/t bleeding from telangiectasias in GI tract
117
Kaposi sarcoma
- Malignant tumor arising from endothelial cells or primitive mesenchymal cells.
- AIDS-defining lesion, MC cancer in AIDS
- A/w HHV8
- Raised red/purple discoloration that progresses from a flat lesion to a plaque to a nodule that ulcerates
- Common sites include skin (MC), mouth, GI
118
Lymphangiosarcoma
Malignancy of lymphatic vessels
| Arises out of long-standing chronic lymphedema
119
Pyogenic granuloma
- Vascular, red pedunculated mass that ulcerates and bleeds easily
- Posttraumatic or a/w pregnancy
120
Spider telangiectasia
Arteriovenous fistula, disappears when body is compressed
| A/w hyperestrinism (cirrhosis, normal pregnancy)
121
Sturge-Weber syndrome
- Nevus flammeus on the face in the distribution of the opthalmic branch and/or maxillary branch of CN V
- Some cases show ipsilateral malformation of pia mater vessels overlying the occipital and parietal lobes, can bleed and produce subarachnoid hemorrhage
122
von Hippel-Lindau syndrome
- cavernous hemangiomas in the cerebellum and retina
| - increased incidence of bilateral pheochromocytoma and bilateral renal cell carcinomas
123
Small vessel vasculitis
- Called leukocytoclastic venulitis or hypersensitivity vasculitis
- Skin overlying vasculitis is hemorrhagic, raised, painful to palpation --> called palpable purpura
- Microscopically: vessel is disrupted and contains neutrophilic infiltrate a/w nuclear debris and fibrinoid necrosis
124
Medium sized vessel vasculitis
- muscular artery vasculitis
| - presents with vessel thrombosis and infarction or aneurysms
125
Large vessel vasculities
- elastic artery vasculitis
| - presents with loss of pulse or stroke
126
Takayasu arteritis
- Granulomatous large vessel vasculitis involving aortic arch vessels
- Young Asian women and children
- Absent upper extremity pulse
- Discrepancy in BP between arms is >10 mmHg
- Visual defects, stroke
- Tx: corticosteroids
127
Giant cell arteritis
- Granulomatous large vessel vasculitis involving superficial temporal and ophthalmic arteries
- Adults >50 years of age
- Temporal headache, jaw claudication
- Blindness on ipsilateral side d/t ophthalmic artery vasculitis
- Polymyalgia rheumatica (normal serum creatine kinase)
- Increased ESR
- Tx: corticosteroids
128
Polyarteritis nodosa
- Necrotizing medium-sized vessel vasculitis involving renal, coronary, mesenteric arteries (spares pulmonary arteries)
- Middle-aged men
- A/w HBsAg, HCV less commonly
- HepB associated is type III hypersensitivity, otherwise cause is unknown
129
Clinical/lab findings/Tx in polyarteritis nodosa
- Vessels are at all stages of acute and chronic inflammation
- Fever commonly present
- Focal vasculitis produces aneurysms
- Organ infarction in kidneys, heart, bowels, skin, testicle
- Angiography and biopsy of lesions confirms Dx
- Tx: corticosteroids, cyclophosphamide in resistant cases
130
Kawasaki disease
- Necrotizing medium-sized vessel vasculitis involving coronary arteries
- Children girls
- Unknown cause, possibly infectious agent precipitating an immune rxn in genetically susceptible individuals
- Leading cause of acquired heart disease in children in developed countries
- Asian children (japanese MC)
- Surpassed acute rheumatic heart disease as MC acquired heart disease in kids
131
Kawasaki disease symptoms/tx
- Fever, erythema and edema of hands and feet convalescing with desquamated rash; cervical adenopathy; oral erythema and cracking of lips; strawberry tongue
- Abnormal ECG
- Tx: IVIG, aspirin, corticosteroids only if 2 courses of IVIG unsuccessful
132
Thromboangiitis obliterans
- Medium sized vasculitis with digital vessel thrombosis and damage to neurovascular compartment
- Genetic
- MC in Israeli Ashkenazi Jews, high morbidity in India, Korea, Japan
- Typically men 25-50 who smoke cigarettes
133
Thromboangiitis obliterans sx/tx
- Lower extremity always involved, resting pain on forefoot is characteristic w/ possible ischemic ulcers or gangrene of foot/toes
- Upper extremity involved in 50% of cases, upper limb ischemia with ulceration and gangrene (amputation common); Raynaud phenomenon
- Tx: smoking cessation essential, IV iloprost, vasodilators (a-blockers, calcium channel blockers)
134
Raynaud disease
- Medium-sized vessel vasculitis involving digital vessels in fingers and toes, possibly tip of nose and ears
- Young women
- Exaggerated vasomotor response to cold or stress
- Paroxysmal digital color changes (white-blue-red sequence)
- Ulceration and gangrene in chronic cases
- Tx: avoid cold temps, calcium channel blockers (nifedipine)
135
Raynaud phenomenon
- Medium-sized vessel vasculitis involving digital vessels in fingers and toes, possibly tip of nose and ears
- Adult men and women, secondary to other diseases
- A/w systemic sclerosis and CREST syndrome
- Digital vasculitis w/ vessel fibrosis, dystrophic calcification, ulceration, gangrene
- Tx: avoid cold temps, calcium channel blockers
136
Wegener granulomatosis
- Necrotizing medium and small-sized vessel vasculitis involving lung and renal vessels
- Mean age 41 years, men = women, ~90% present with Sx involving upper/lower airways or both
137
Wegener granulomatosis Sx, Tx
- Necrotizing granulomas in skin, upper respiratory tract (saddle nose deformity, chronic sinusitis, collapse of trachea) and lower respiratory tract (cavitating nodular lesions)
- Necrotizing vasculitis in lungs (infarction, hemoptysis; lung most reliable source for biopsy to secure Dx), kidneys (crescentic glomerulonephritis), c-ANCA antibodies correlate erratically w/ therapy
- Tx: corticosteroids, cyclophosphamide
138
Microscopic polyangiitis
- Small vessel vasculitis involving skin, lung, brain, GI tract, kidneys
- Children and adults
- Precipitated by drugs, infections, immune disorders
- Vessels at SAME stage of inflammation
- Palpable purpura, glomerulonephritis (crescentic type), p-ANCA antibodies
- Tx: corticosteroids, cyclophosphamide
139
Churg-Strauss syndrome
- Small vessel vasculitis involving skin, lung, heart vessels
- Mean age 51, probably autoimmune
- Allergic rhinitis, asthma
- p-ANCA antibodies, eosinophilia
- Tx: corticosteroids. w/ treatment, 1-year survival is 90%, 5-year survival ~60%
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Henoch-Schonlen purpura
- Small vessel vasculitis involving skin, GI tract, renal, joint vessels
- Usually in children 1-15 years, peak incidence in spring, rarely summer
- Males > females
- MC vasculitis in children
- MC in whites and Asians than blacks
- IgA-anti-IgA immunocomplexes (type III hypersensitivity)
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Henoch-Schonlein purpura Sx, Tx
- Offen follows viral URI, group A streptococcal pharyngeal infxn. Pathogens may act as an antigen trigger that causes antibody formation --> immunocomplex formation
- Palpable purpura of buttocks and lower extremities is characteristic
- Polyarthritis, glomerulonephritis, abdominal pain and vomiting, GI bleeding
- Recurrence in 1/3 of cases
- Most have spontaneous recovery in 4 months w/o therapy
- Tx: corticosteroids used if severe GI disease or renal disease are present
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Cryoglobubulinemia
- Small vessel vasculitis involving skin, GI tract, renal vessels
- Different types: mixed, monoclonal, polyclonal)
- Adults, female>male
- Associated w/ HCV, type 1 MPGN, multiple myeloma (monoclonal type), lymphoproliferative disorders, connective tissue disorders
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Cryoglobulinemia Sx, Tx
- Cryoglobulins: they are proteins in plasma that gel at cold temps, esp. in areas exposed to cold temps
- Palpable purpura, acral cyanosis of nose and ears and Raynaud phenomenon
- Glomerulonephritis (crescentic type), arthritis, abdominal pain
- Tx: immunosupressive agents
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Infectious vasculitis
- Small vessel vasculitis involving skin vessels
- Children and adults
- Involves all microbial pathogens
- Rocky Mountain Spotted fever
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Infectious vasculitis (RMSF) pathogenesis, Sx, Tx
- Dog tick or wood tick transmits Rickettsia rickettsii
- Organisms invade endothelial cells producing vasculitis
- Fever is universally present
- Petechiae begin on palms and spread to trunk
- Tx: oral doxy
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Infectious vascutis N. meningitidis Sx, Tx
- Disseminated meningococcemia
- Capillary thromboses, usually in setting of DIC, produce petechiae that become confluent ecchymoses as disease progresses
- Hemorrhagic infarctions of both adrenal glands commonly occurs producint acute hypocortisolism and death (Waterhouse-Friderichsen syndrome)
- Tx: IV penicillin G
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Hypertension
- Essential hypertension is 85%, secondary is 15%
| - Normal BP:
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What does systolic blood pressure correlate with?
Stroke volume and compliance of the aorta
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Primary determinants of SV:
1. preload, or the volume of blood in the LV
2. afterload, or the resistance the LV contracts against to eject blood from the heart
3. Contractility of the heart
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What determines compliance of the aorta?
Vessel elasticity
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What the fuck is compliance of the aorta
The ability of the aorta to expand with blood during systole
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What happens to compliance with age?
Decreases d/t reduced elasticity of the aorta
| - Mechanism for systolic hypertension in people >60
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Causes of increased SBP
- Increased preload
- Increased contractility
- Decreased compliance of aorta
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Causes of decreased SBP
- Decreased preload
- Decreased contractility
- Increased afterload
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What does diastolic BP correlate with?
- The volume of blood in the aorta during diastole
- Primarily depends on the state of contraction (tonicity) of the SMCs in the peripheral vascular resistance arterioles, the viscosity of the blood, and the HR
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What causes increased DBP?
- Vasoconstriction of PVR arterioles --> greater volume of blood is present in artery while heart is filling up
- Increase in blood viscosity
- Increase in HR --> decreases filling of coronary arteries, leaving greater volume of blood in aorta during diastole
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What causes decreased DBP?
- Vasodilation of PVR arterioles
- Severe anemia --> decreases blood viscosity
- Decreasing HR
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Role of sodium in HTN
- Excess sodium increases plasma volume --> increased SV --> increased SBP
- Excess sodium produces vasoconstriction of PVR arterioles -->increased DBP
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Essential HTN
- More common in blacks
- Genetic factors reduce renal sodium excretion
- Decreased Na excretion --> increased PV--> increased SV --> increased SBP
- Decreased Na excretion --> vasoconstriction of PVR arterioles --> increased DBP
Other factors: obesity, stress, smoking, salt intake, lack of exercise
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Adrenal causes of secondary HTN
- Cushing syndrome: increased mineralocorticoids
- Pheochromocytoma: increased catecholamines
- Neuroblastoma: increased catecholamines
- 11-hydroxylase deficiency: increased mineralocorticoids
- Primary aldosteronism: increased aldosterone
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Aortic causes of secondary HTN
- Postductal coarctation: activation of RAA system
| - Elderly: systolic HTN d/t decreased elasticity of aorta
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CNS causes of secondary HTN
Intracranial hypertension: release of catecholamines
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Drug causes of secondary HTN
Oral contraceptives: increased synthesis of angiotensinogen
| Cocaine: increased sympathetic activity
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Parathyroid causes of secondary HTN
Primary hyperparathyroidism: calcium increases peripheral resistance arteriole SMC contraction
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Pregnancy causes of secondary HTN
Preeclampsia: increased angiotensin II
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Renal causes of secondary HTN
Renovascular disease: atherosclerosis, fibromuscular hyperplasia
- In both, there is epigastric bruit d/t blood being forced thru narrow lumen
- Activation of RAAS
Renal parenchymal disease: eg. diabetic nephropathy, adult polycystic kidney disease, glomerulonephritis, retention of sodium
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Cardiovascular complications of HTN
- LV hypertrophy: MC overall complication
- acute MI: MC cause of death
- atherosclerosis
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CNS complications of HTN
- Intracerebral hematoma: d/t rupture of Charcot-Bouchard aneurysm
- Berry aneurysm: rupture produces subarachnoid hemorrhage
- Lacunar infarct: small infarcts d/t hyaline arteriolosclerosis
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Renal complications of HTN
- Benign nephrosclerosis: kidney disease of HTN d/t hyaline arteriolosclerosis. Atrophy of tubules and sclerosis of glomeruli --> renal failure
- Malignant hypertension: rapid increase in BP accompanied by renal failure and cerebral edema
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Eye complications of HTN
- Hypertensive retinopathy: AV nicking, hemorrhage of retinal vessels, exudates, papilledema
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Sequence of events in hypertensive retinopathy
1. Thickening of arteriole, smaller diameter, narrow column of blood --> flame hemorrhage, exudates, papilledema
2. Copper wiring, smaller diameter, wider light reflex
3. Silver wiring, smaller diameter, no blood visible
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Keith-Wagener-Barker classification of hypertensive retinopathy
Grade I: focal narrowing of arterioles, mild AV nicking
Grade II: Arteriole narrowing, copper wiring, AV nicking more noticeable
Grade III: arteriole narrowing, silver wiring, hemorrhages, soft and hard exudates, disappearance of vein under arteriole, normal disk
Grade IV: arterioles are fine fibrous cords, same as grade III except papilledema is present
