Block 6 Week 1 Monday - Atherosclerosis & Hypertensive Vascular Disease

Front 1

What are the 3 type of arteries?

Back 1

Elastic, muscular, & arterioles

Front 2

What type of arteries are the largest & what are they prone to?

Back 2

Elastic arteries are the largest & are prone to aneurysms.

Front 3

What are the intermediate sized arteries and what are they prone to?

Back 3

Muscular arteries are intermediate in size & are prone to atherosclerosis.

Front 4

What are the smallest arteries & what are they prone to?

Back 4

Arterioles are the smallest arteries and are prone to hypertensive changes.

Front 5

How is the resistance to flow related to the diameter of blood vessels?

Back 5

Resistance to flow is inversely proportional to the 4th power of the diameter.

Front 6

From aorta to capillaries, how does the cross-sectional cumulative luminal area change? How does the flow rate change?

Back 6

From aorta to capillaries, cross-sectional area increases but flow rate decreases.

Front 7

What are the 3 layers of blood vessels?

Back 7

endothelium, tunica media, tunica adventitia

Front 8

What is the blood supply to blood vessels?

Back 8

vaso vasorum

Front 9

what are 3 components of tunica media?

Back 9

internal elastic membrane (lamina), muscular & elastic tissue, & external elastic membrane (lamina)

Front 10

What does a histo slide of the largest arteris (aorta) look like?

Back 10

Elastic arteries are thickened, with parallel estastic fibers that give it elasticity & strength

Front 11

What sized arteries are muscular arteries & what are they prone to?

Back 11

intermediate sized arteries - prone to atherosclerosis

Front 12

Is the vascular system static?

Back 12

No, vascular system is NOT static, there is new growth = plasticity

Front 13

What are the 3 main functions of endothelium?

Back 13

1)barrier function
2)transport function
3)metabolic function

Front 14

What type of cholesterol is proatheroscleotic & what do endothelial cells to to this cholesterol?

Back 14

LDL is found in plaques & thought to be proatherosclerotic. Endothelial cells oxidize LDL so macrophages & SMC can injest it.

Front 15

How do endothelial cells prevent thrombosis?

Back 15

Maintain vascular integrity

Front 16

What are 3 components involved in forming clots?

Back 16

coagulation factors, platelets, & endothelial cells

Front 17

What happens if there when there is endothelial injury?

Back 17

There is a loss of antithrombic function of endothelial cells.

Front 18

What is exposed in endothelial injury?

Back 18

there is exposure of underlying collagen & von Wilebrand factor so platelets can bind and form an initial hemostatic plug.

Front 19

How do platelets recruit other platelets to the site?

Back 19

ADP & TxA2 (thromboxane A2)

Front 20

What is the end result of clotting cascade?

Back 20

thrombin cleaves fibrinogen to fibrin, which help create a more stable fibrin clot.

Front 21

What antithrombotic prostaglandin do endothelial cells release?

Back 21

Prostaglandin I2

Front 22

What is the most common form of arteriosclerosis?

Back 22

Atherosclerosis

Front 23

How many deaths is the US are related to atherosclerosis?

Back 23

50% of deaths in US

Front 24

What is progression of atherosclerosis like?

Back 24

chronic, slowly progressive disease

Front 25

What type of arteries does atherosclerosis affect?

Back 25

large & medium sized arteries

Front 26

What are the common sites of atherosclerosis?

Back 26

commonly at sites of hemodynamic turbulance (ex. bifrications)

Front 27

What layer of the blood vessels does atherosclerosis affect?

Back 27

INTIMAL disease

Front 28

What are 4 componets involved in atherosclerosis?

Back 28

1) smooth muscle
2) lipid
3) connective tissue
4) macrophages

Front 29

What are 5 steps in the evolution of atherosclerosis?

Back 29

1) endothelial dysfunction
2) lipid accumulation, smooth muscle cell proliferation in intima
3) lipids cause cell injury so macrophages enter
4) macrophages scavenge extracellular lipid & release growth factors (FGF, TNF, IL-1, interferon, TGF-B)
5) eventual damage to endothelium causeing platelet adherence

Front 30

What happens to the intima?

Back 30

it thickens

Front 31

What are lipid-laden macrophages?

Back 31

Foam cells

Front 32

What are 2 possible precursors of atherosclerosis?

Back 32

1) fatty streak
2) intimal cell mass

Front 33

What are pros & cons of fatty streaks as atherosclerotic precursor?

Back 33

Pros: composed of foamy macrophages (lipid) & they're seen in children & adults

Cons: Thoracic > abdominal aorta, seen in regions of low prevalence of atherosclerosis

Front 34

What are pros & cons of intimal cell mass as atherosclerotic precursor?

Back 34

Pro: Nodules of intimal smooth muscle at arterial branch points

Cons: May only be age-related change; no lipid depostion

Front 35

What are the 6 pathogenesis hypotheses of atherosclerosis?

Back 35

1) Insudation hypothesis
2) Encrustation hypothesis
3) Rxn to injury hypothesis
4) Monoclonal hypothesis
5) Intimal cell mass hypothesis
5) Hemodynamic hypothesis

Front 36

(1) What is the Insudation hypotheis?

Back 36

lipid in atherosclerotic lesions is derived from plasma lipoproteins, esp LDL (doesn't explain SMC proliferation, ect)

Front 37

(2) What is the encrustation hypothesis?

Back 37

(involves platelets) - small mural thrombi represent initial event of atherosclerosis [not true but thrombi involved LATE in progression, such as occlusion)

Front 38

(3) What is Rxn to injury hypothesis?

Back 38

injury of endothelial cells is primary event - macrophages & endothelial cells release growth factors that are chemotactic for SMC & tell SMC to proliferate

Front 39

(4) What is monoclonal hypothesis?

Back 39

SMC (1 or a few) are stimulated to proliferate (possibly due to virus); increased SMC that come from same cell

Front 40

(5) What is the intimal cell mass hypothesis?

Back 40

Intimal cell mass (SMCs) as precursors to atherosclerosis

Front 41

(6) What is hemodynamic hypothesis?

Back 41

low shear areas when blood fluctuates rapidly more prone to atherosclerosis - increased BP role in atherosclerosis - physical damage from hypertension

Front 42

What are slit-like features seen in an atherosclerotic vessel?

Back 42

cholesterol clefts

Front 43

What are 5 sites of atherosclerotic disease of lg & med sized arteries in order of frequency?

Back 43

1) abdominal aorta & iliac arteries
2) proximal coronary arteries
3) throacic aorta, femoral & popliteal artieris
4) Internal carotid arteries
5) vertebral, baisilar, & middle cerebral artery

Front 44

At what sites is atherosclerosis common?

Back 44

Sites of hemodynamic turbulence

Front 45

What are 6 complications of atherosclerosis?

Back 45

1) Thrombosis (acute occlustion) (ex. MI or CVA)
2) Chronic stenosis (ischemia) (ex. angina)
3) Hemorrhage (into plaque)
4) Aneurysm formation
5) Ulceration (w/ atheroemboli) (ex. leads to losing a toe)
6) Calcification

Front 46

What are 6 common places/organs of extreme complication with atherosclerosis & what are the complications?

Back 46

1) brain - stroke
2) kidney - infarct
3) Abnominal Aortic Aneurismal rupture leading to death
4) occlusion of peripheral vessel in foot causing ulceration
5) occlusion of colonic vessel leading to ischemia of bowels
6) occlusion of coronaries leading to MI

Front 47

What can arterial stenosis of a peripheral vessel lead to?

Back 47

chronic ischemia (ulceration on skin)

Front 48

Where is a common place for an aortic aneurysm?

Back 48

AAA - infrarenal

Front 49

What gross appearance might a kidney have that is affected ischemically due to atherosclerosis?

Back 49

cortex of kidney might have a granular appearance

Front 50

What are 3 non-modifiable risk factors for atherosclerosis?

Back 50

1) Age
2) sex (M>F)
3) genetics

Front 51

What are 6 modifiable risk factors?

Back 51

1) diet
2) lifestyle (personality type, exercise habits)
3) hyperlipidemia (cholesterol>triglicerides)
4) hypertension (esp after age 40)
5) cigarette smoking
6) diabetes mellitus

Front 52

Which 4 modifiable risk factors are physican's most importantly involved with?

Back 52

1) hyperlipidemia (cholesterol>triglicerides)
2) hypertension (esp after age 40)
3) cigarette smoking
4) diabetes mellitus

Front 53

What are the names of essential lipids?

Back 53

cholesterol & triglycerides are essential

Front 54

Are cholesterol & triglycerides soluble?

Back 54

No, Cholesterol & triglycerides are insoluble, need transport system

Front 55

How much of total body cholesterol is contained in the plasma?

Back 55

Plasma contains 7% of total body cholesterol

Front 56

How does LDL & HDL correlate with atheroslerosis?

Back 56

LDL level correlates directly w/ atheroslerosis (exp oxidized LDL)
HDL level correlates inversely with atherosclerosis

Front 57

What are the 5 ways in which lipids are carried in the body from largest to smallest size?

Back 57

1) chylomicron
2) VLDL
3) IDL
4) LDL
5) HDL

Front 58

What are the lipids & apoproteins of chylomicrons?

Back 58

80 - 90% TG (dietary)
C proteins, AI, AII, B48

Front 59

What are the lipids & apoproteins of VLDL?

Back 59

45 - 65 % TG (endogenous)
25% cholesterol
C proteins, (B48/B100?), E

Front 60

What are the lipids & apoproteins of IDL?

Back 60

45% cholesterol
B100, E

Front 61

What are the lipids & apoproteins of LDL?

Back 61

70% cholesterol
B100

Front 62

What are the lipids & apoproteins of HDL?

Back 62

<25% cholesterol
AI, AII

Front 63

What is involved in the exogenous pathway of lipid metabolism?

Back 63

cholesterol absorbed from intestine is carried by chylomicrons (B48) to capillaries, where lipoprotein lipase breaks up chylomicrons in to remnants which are taken into the liver

Front 64

How does cholesterol leave the liver & where does LDL made?

Back 64

Cholesterol leaves liver as VLDL, is broken up in capillaries by LPL into IDL, and then further to LDL (B100).

Front 65

What are 2 possible fates of LDL in the blood?

Back 65

LDL can be taken up by the liver or stored in extraheptaic tissues.

Front 66

Where does HDL come from?

Back 66

Extrahepatic tissues release cholesterol by HDL, which is then transformed in plasma by LCAT to IDL, then to LDL, which can be taken up by liver or extrahepatic tissues.

Front 67

Will an increase in chylomicrons increase atherogenicity?

Back 67

NO

Front 68

Will an increase in LDL increase atherogenicity? Increased VLDL increase atherogenicity?

Back 68

Yes! When mutations occur in LDL receptors, ect. increased LDL increases atherogenicity;
Increased VLDL has a slight increase in atherogenicity

Front 69

What is a cholesterol genetic disease in which LDL receptors are malfunctioning due to a mutation?

Back 69

Familial Hypercholesterolemia (Type II)

Front 70

What are the genetics of Family Hypercholesterolemia Type 2? [how is it passed? what chrom?]

Back 70

Autosomal dominant, many different mutations, genes on short arm of chromosome 19

Front 71

How many heterozygotes for FH2 are there? How high is their cholesterol? When do they get CVD?

Back 71

Heterozygotes 1:500
Cholesterol is 2 x normal
Cardiovascular disease in 30s & 40s

Front 72

How many homozygotes for FH2 are there? How high is their cholesterol? When do they get CVD?

Back 72

1:1,000,000
have cholesterol 4-6 x normal
Cardiovascular disease in childhood

Front 73

How are LDLs processed in FH2?

Back 73

Elevated LDLs are processed via receptor-independent pathway

Front 74

What might occur on someone's face or knees, ect that has familial hyperlipidemia?

Back 74

xanthomas

Front 75

What are secondary causes of hyperlipoproteinemia?

Back 75

HYPOTHYROIDISM, diabetes mellitus, nephrotic syndrome, renal failure (uremia), alcoholism, obstructive liver disease, pancreatitis, dysglobulinemia, glycogen storage disease, porphyria

Front 76

What are 3 current areas of focus on theories of atherosclerosis?

Back 76

1) Inflammatory/Immune Factors
2) Chronic Infection
3) Homocysteine

Front 77

What are 3 Inflammatory/Immune factors that are increased in atherosclerosis?

Back 77

1) IL-1, IL-6 increased
2) C-reactive protein increased
3) Macrophage colony stimulating factor increased

Front 78

What are 3 infectious ageants that may be involved in chronic infections leading to atherosclerosis?

Back 78

1) chlamydia pneumoniae
2) Helicobacter pylori
3) CMV

Front 79

What is the theory of how homocysteine might be involved in atherosclerosis?

Back 79

Increased levels of homocycteine are associated w/ atherosclerosis, possibly via increasing oxidized LDLs

Front 80

What 6 complications have been associated with hypertension?

Back 80

1) Atherosclerosis
2) Angina pectoris
3) Sudden cardiac death (arrhythmia due to hypertension)
4) Aortic dissection
5) Cerebral infarction
6) Intracerebral hemorrhage

Front 81

What is the pathogenesis of hypertension?

Back 81

95% idiopathic (don't know cause)
5% renal disease, renovascular, endocrine-related, other

Front 82

How is BP related to CO & TPR?

Back 82

BP = CO x TPR

CO = HR x SV

Front 83

What are cardiac & blood volume factors that affect cardiac output?

Back 83

Cardiac factors: HR & contractility

Blood Volume: sodium, mineralocorticoids, atriopeptin

Front 84

What are local factors that affect peripheral resistance (TPR)?

Back 84

autoregulation,
Ionic (pH, hypoxia)

Front 85

What are humoral factors (5 constrictors & 3 dilators) that affect peripheral resistance?

Back 85

Constrictors: angiotensin II, catecholamines, thromboxane, leukotrienes, endothelin
Dilators: prostaglandins, kinins, NO/EDRF

Front 86

What are neural factors (1 constrictor, 1 dilator) that affect peripheral resistance?

Back 86

Constrictor: alpha-adrenergic
Dilator: beta-adrenergic

Front 87

What are JNC 7 standards for normal BP?

Back 87

<120 & <80

Front 88

What is prehypertension? Should you give meds?

Back 88

120-139 or 80-89
Drugs only for compelling indications. Most people - no drugs.

Front 89

What is stage 1 hypertension? Should you give meds?

Back 89

140-159 or 90-99
Most patients should get thiazide drugs. Give additional meds in compelling indications.

Front 90

What is stage 2 hypertension? What drugs do you give?

Back 90

> or = 160 or
> or = 100
2 drug combo for most people thiazide + (ACEI, ARB, BB, or CCB)

Front 91

What are 4 identifiable causes of hypertension?

Back 91

1) renal
2) endocrine
3) cardiovascular
4) other

Front 92

What are 2 renal conditions that may cause hypertension?

Back 92

1) chronic renal disease (increased renin)
2) renovascular disease

Front 93

What are 4 endocrine conditions that could cause hypertension?

Back 93

1) primary aldosteronism
2) chronic steroid therapy, cushing syndrome, congenital adrenal hyperplasia
3) pheochromocytoma (tumor of adrenal medulla,increases epi)
4) thyroid or parathyroid disease

Front 94

What are 2 cardiovascular conditions that might cause hypertension?

Back 94

1) coarction of the aorta (legs low BP, arms high BP)

Front 95

What are 2 other causes of hypertension?

Back 95

1) sleep apnea
2) drug-induced or drug-related

Front 96

How & what produces renin?

Back 96

decreased vascular tone causes sympathetic stim & macular densa feedback to JG cells that secrete renin.

Front 97

What does renin do?

Back 97

renin converts angiotensinogen (constantly secreted by liver) to angiotensin I, which is converted by ACE in lungs to angiotensin II.

Front 98

What is the end result of angiotensin II & what are 2 ways in which it accomplishes this goal?

Back 98

goal of angiotensin II is to increase BP by
1) vasoconstriction (directly)
2) increase aldosterone, which increases Na retention

Front 99

What are 2 ways in which hypertension chronically changes blood vessels?

Back 99

1) hyaline arterisoclerosis (benign arteriosclerosis)
2) hyperplastic arteriosclerosis
(malignant arteriosclerosis)

Front 100

What often causes hyaline arteriolosclerosis? What physically happens?

Back 100

Often caused by benign (chronic) hypertension
Hyaline material in vessel walls, basement membrane thickening

Front 101

Is hyaline arteriolosclerosis specific to hypertension?
What might hyaline arteriolosclerosis do to the kidney?

Back 101

Nonspecific, can be seen in old age, diabetes mellitus.
May cause chronic renal insufficiency via arteriolar nephrosclerosis (surface of kidney becomes granular).

Front 102

How can hyaline arteriolosclerosis affect the glomerulus?

Back 102

decreased blood flow leads to sclerosis of the glomerulus & decreased functin of glomeruls & a scar is formed

Front 103

Hyperplastic arteriolosclerosis:
What type of necrosis?
What does it look like?
What is it a reaction to?
What might affected vessels do?

Back 103

Hyperplastic arteriolosclerosis:
fibrinoid necrosis
"onion-skin" arterioles
reaction to pressures
affected vessels may rupture

Front 104

What type of hypertension might you see hyperplastic arteriolosclerosis?
What sign/symptoms may also occur?

Back 104

Seen in malignant (accelerated) HTN = rapidly progressive HTN.
Headache, blurred vision, malaise
(30s or 40s)

Front 105

When do you worry about cerebral hemmorrhage?

Back 105

systolic >200, diastolic >100

Front 106

What causes onion skin appearance in hyperplastic arteriolosclerosis?

Back 106

reduplication of internal elastic membrane

Front 107

How might hyperplastic arteriolosclerosis affect the kidney? The brain?

Back 107

kidney: fibrinoid necrosis in afferent arterioles can damage glomeruli
Brain: intra-cerebral hemorrhage

Front 108

In what arterial disease do elderly individuals get in which there is degenerative calcification of the media?

Back 108

Monckeberg's Medial Calcific Sclerosis

Front 109

Does Monckeberg's medial calcific sclerosis affect the intima or lumen?

Back 109

No effect on intima or lumen, only affects the media (calcified media)

Front 110

What might an x-ray of a patient with Monckeberg's medial sclerosis look like?

Back 110

May account for incidental vascular calcification seen on x-rays in medium-sized artieris.

Front 111

What arterial disease typically affects women of reproductive age?

Back 111

Fibromuscular dysplasia

Front 112

In fibromuscular dysplasia, what sized arteries are affected & what do they look like? What specific arteries are usually affected?

Back 112

segments of irregular wavy thickening of medium-sized arteries
Renal, carotid arteries typically affected

Front 113

Besides women of reproductive age, what other type of patients might get fibromuscular dysplasia?

Back 113

Patients with alpha-1-antitrypsin deficiency

Front 114

What 2 complications might you worry about in a patient who has fibromuscular dysplasia?

Back 114

1) renovascular hypertension
2) arterial dissection