Path 11S488-510

Front 1

what can hypotension lead to

Back 1

inadequate organ perfusion then dysfunction or death

Front 2

what can hypertension lead to

Back 2

vessel and end-organ damage

Front 3

BP above what limits is considered as increased risk of atherosclerosis

Back 3

sustained diastolic above 89 mmHg and systolic above 139 mmHg

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when are lower thresholds for BP applicable

Back 4

in patients with other risk factors like diabetes

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what causes essential hypertension

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unknown; combined effects of multiple genetic polymorphisms and interacting environmental factors

Front 6

If untreated, what is the clinical outcome of half od hypertensive patients

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die of ischemic heart disease or CHF (another 1/3 of stroke)

Front 7

accelerated/malignant hypertension

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rapidly rising BP, when untreated leads to death in 1-2 years

Front 8

characteristics of accelerated hypertension

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BP >200/120; renal failure, retinal hemorrages and exudates; generally superimposed on pre-existing benign hypertension

Front 9

What is peripheral vascular resistance affected by

Back 9

neural and horonal factors

Front 10

humoral vasoconstricting influences

Back 10

angiotensin II, catecholamines, endothelin

Front 11

vasodilators

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kinins, prostaglandins, NO

Front 12

what does the renin-angiotensin system affect

Back 12

peripheral resistance and sodium homeostasis

Front 13

when and where is renin secreted

Back 13

by the JG cells of kidney in response to fall in BP

Front 14

3 actions of angiotensin II

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vascular smooth muscle contraction, aldosterone secretion stimulation, distal tubular reabsorption of Na

Front 15

why does decreased blood volume cause increased reabsorption of Na by proximal tubules

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glomerular filtration rate falls (basically blood goes slower allowing more time for Na to be reabsorbed)

Front 16

What do atrial and ventricular myocardium release in response to volume expansion

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natriuretic factors

Front 17

what are the actions of natriuretic factors

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inhibit Na reabsoption in distal tubules and induce vasodilation (endogenous inhibitors of renin-angiotensin system)

Front 18

What reabsorbes 98% of Na in kidneys

Back 18

ion channels, exchangers, and transporters constitutively active and not subjet to regulation

Front 19

Where is the remaining 2% reabsorbed?

Back 19

epithelial Na+ channel (ENaC) in the cortical collecting tubule (tightly regulated by renin-angiotensin system)

Front 20

Where are genetic defects affecting aldosterone metabolism and increasing aldosterone secretion

Back 20

aldosterone synthase, 11B-hydroxylase, 17a-hydroxylase; all cause hypertension

Front 21

Liddle syndrome

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mutations in epithlial Na+ channel protein that leads to increased distal tubular reabsorption of Na+ induced by aldosterone; causes hypertension

Front 22

exogenous factors in hypertension

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stress, obesity, physical inactivity, heavy consumption of salt

Front 23

one of the most common causes of secondary hypertension

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primary aldosteronism

Front 24

2 forms of small blood vessel disease associated with hypertension

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hyaline arteriolosclerosis and hyperplastic arteriolosclerosis

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hyaline arteriolosclerosis

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plasma protein leakage across injured endothelial cells and increased smooth muscle cell matrix synthesis in response to chronic hemodynamic stress

Front 26

what other common disease causes hyaline arteriolosclerosis and what causes it

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diabetic microangiography; hyperglycemia induced endothelial cell dysfunction

Front 27

nephrosclerosis due to chronic hypertension

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arteriolar narrowing of hyaline arteriolosclerosis causes diffuse impairment of renal blood supply and causes renal scarring

Front 28

hyperplastic arteriolosclerosis

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occurs in malignant hypertension; vessels exhibit 'onion-skin' lesions-consist of smooth muscle cells with thickened, reduplicated basement membranes

Front 29

necrotizing arteriolitis

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fibrinoid deposits and vessel wall necrosis, particularly in the kidney

Front 30

arteriosclerosis

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generic term describing arterial wall thickening and loss of elasticity

Front 31

3 general patterns of arteriosclerosis

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1) arteriolosclerosis 2) Monskeberg medial sclerosis 3) atherosclerosis

Front 32

arteriolosclerosis

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affects small arteries and arterioles (hyaline and hyperplastic variants)

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Monskeberg medial sclerosis

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calcific deposits in muscular arteries; generally in patients >50; deposits may undergo metaplastic change into bone; do not encroach on vessel lumen and are usually not clinically significant

Front 34

Atherosclerosis

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most frequent and clinically important pattern

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atheromas

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intimal lesions that protrude into vessel lumens

Front 36

increased risk of atherosclerosis with 2 or 3 risk factors

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4 times, 7 times increased risk

Front 37

modifiable risk factors in IHD

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hyperlipidemia, hypertension, cigarette smoking, diabetes

Front 38

what are dietary sources high in cholesterol and saturated fats

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egg yolks, animal fas, butter

Front 39

what raises/lowers HDL levels

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exercise and moserate ethanol consumption; obstiry and smoking

Front 40

what class of drugs lowers cholesterol

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statins

Front 41

mechanism of statins

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inhibit hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase (the rate limiting enzyme in cholesterol biosynthesis)

Front 42

other risk factors for cardiovascular events

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inflammation, hyperhomocystinemia, metabolic syndrome, lipoprotein (a), factors affecting hemostasis, others

Front 43

C-reactive protein

Back 43

circulating marker of inflammation that correlates with IHD risk

Front 44

What is CRP

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acute-phase reactant synthesized primarily by liver; role in innate immune response

Front 45

what role does CRP play in innate immune response

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opsonizing bacteria and activating complement

Front 46

How does CRP contribute to atherosclerosis

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can activate local endothelial cells and induce a prothrombic state and increase adhesiveness of endothelium for leukocytes

Front 47

what can cause high homocysteine levels

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low folate and vitamin B12 intake

Front 48

what is lipoprotain (a)

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modified LDL that contains apolipoprotein B-100 portion of LDL linked to apolipoprotein A

Front 49

2 hypotheses of artherosclerosis mechanism

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1) intimal cellular proliferation 2) repetative formation and organization of thrombi

Front 50

atherosclerosis is produced by (7 steps)

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1) endothelial injury 2) accumulation of lipoproteins 3) monocyte adhesion 4) platelet adhesion 5) factor release 6) smooth muscle proliferation and ECM production 7) lipid accumulation

Front 51

where do early atheromas begin

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sites of morphologically intact endothlium; thus endothelial dysfunction underlies human artherosclerosis

Front 52

two most important causes of endothelial dysfunction

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hemodynamic disturbances and hypercholesterolemia

Front 53

why do plaques tend to occur at ostia of existing vessels

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1) disturbed flow patterns 2) endothelial gene products (like antioxidant superoxide dimutase)

Front 54

common lipoprotein abnormalities in the general population

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1) increased LDL cholesterol levels 2) decreased HDL cholesterol levels 3) increased levels of lipoprotein (a)

Front 55

what are the dominant lipids in atheromas

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cholesterol and cholesterol esters

Front 56

how does hypercholesterolemia cause atheroscerosis

Back 56

directly impair endothelial cell fxn by increasing local oxygen free radical producation (injure tissues and accelerate NO decay)

Front 57

how does LDL become oxidized

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via free radicals generated by macrophages or endothelial cells

Front 58

what does oxidized LDL stimulate

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release of GFs, cytokines, chemokines by endothelial cells and macrophages and increase monocyte recruitment

Front 59

LDL oxidation cycle

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oxidized LDL recruits monocytes, monocytes arrive and engulf potentially harmful oxidized LDLs, monocytes secrete factors that recruit more monocytes and cause oxidation of more LDL

Front 60

growth factors implicated in smooth muscle cell proliferation and ECM synthesis

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PDGF, FGF, TGF-alpha

Front 61

what is PDGF released by

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locally adherent platelets, macrophages, endothelial cells, and smooth muscle cells

Front 62

what is the main ECM product smooth muscle cells synthesize

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collagen; stabilizes plaques

Front 63

fatty streaks

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earliest lesions in atherosclerosis; lipid-filled foamy macrophages

Front 64

most extensively involved vessels in atherosclerosis

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lower abdominal aorta, coronary arteries, cicle of Willis

Front 65

vessels ususally spared by atherosclerosis

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upper extremities, mesenteric, and renal arteries (except at ostia)

Front 66

3 components of atherosclerotic plaques

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1) cells including smooth muscle cells, macrophages, and T cells 2) ECM including collagen, elastic fibers, and proteoglycans 3) intra and extracellular lipid

Front 67

what are plaques susceptable to?

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rupture, ulceration, erosion…thrombosis

Front 68

what percent occlusion generally occurs before demand exceeds supply

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~70%

Front 69

intermittent claudication

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diminished extremity perfusion

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intrinsic factors that trigger abrupt changes in plaque configuration

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structure and configuration

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extrinsic factors that trigger abrupt changes in plaque configuration

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BP, platelet reactivity

Front 72

what affects cap stability

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balance of collagen synthesis to degradation

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what determines collagen turnover

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metalloproteinases (MMPs) elaborated by macrophages

Front 74

inhibitors of MMPs (TIMPs)

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produced by endothelial cells, smooth muscle cells, and macrophages

Front 75

statin affect on plaques

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may stabilize plaques in addition to lowering cholesterol levels

Front 76

what does aadrenergic stimulation do

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increase BP, induce local vasoconstriction

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peak onset of MI

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6 am and 12 pm

Front 78

what can cause vasoconstriction

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1) circulating adrenergic agonists 2) locally released platelet contents 3) impaired secretion of endothelial cell relaxing factors relative to contracting factors 4) mediators from perivascular inflammatory cells

Front 79

vascular pathology results via what 2 principle mechanisms

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1) narrowing or complete obstruction (either progressive or acute) 2) weakening of vessel walls (dilation and rupture)

Front 80

arterial wall

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thickness gradually diminishes as vessels become smaller, but ratio of thickness to diameter become greater

Front 81

what separates the intima from the media

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internal elastic lamina

Front 82

what generaaly separates arterial media from adventicia

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external elastic lamina

Front 83

what is in the adventicia

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CT with nerve fibers and vasa vasorum

Front 84

Three categories of arteries

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1) large/elastic arteries 2) medium/muscular arteries 3)small arteries (less than 2mm) and arterioles (20-200 um)

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where are most structural variations in arteries due to local adaptations

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in the media and ECM

Front 86

ectatic

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dialated

Front 87

how are resistance and arteriole diameter related

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halving diamter increases resistance 16 fold

Front 88

diffusion of oxygen become ineffecient at what distance

Back 88

100 um

Front 89

What layers are present in capillaries

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endothelial cell lining, NO media

Front 90

Where does vascular leakage and leukocyte exudation occur in general

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postcapillary venules

Front 91

what vessels does atherosclerosis generally affect

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elastic and muscular arteries

Front 92

what vessels does hypertension generally affect

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small muscular arteries and arterioles

Front 93

what 3 processes characterize blood vessel formation and remodeling

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vasculogenesis, angiogenesis, arteriogenesis

Front 94

vasculogenesis

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formation of blood vessles during embryogenesis

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angiogenesis

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new vessel formation in maature organism; aka neovascularization

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arteriogenesis

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remodeling of existing arteries

Front 97

significant congenital vascular anomalies (no necessarily common)

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1) developmental or berry aneurysms 2) arteriovenous fistula 3) fibromuscular dysplasia

Front 98

fibromuscular dysplasia

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foal irregular thickening of wall of medium and large muscular arteries (renal, carotid, etc)

Front 99

Weibel-Palade bodies

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intracellular membrane-bound storage organelles for von Willebrand's factor in endothelial cells

Front 100

activities of vascular endothelium

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maintain nonthrombogenic blood-tissue interface, modulate vascular resistance, metabolize hormones, regulate inflammation, affect growth of other cell types

Front 101

how can the tight jxns btwn endothelial cells be loosened

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high BP, vasoactive agents (histamine),

Front 102

where can you find fenestrated capillaries

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liver sinusoids or renal glomeruli

Front 103

promoters of vascular smooth muscle cells

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PDGF, endothelin-1, thrombin, FGF, interferon-gamma, IL-1

Front 104

inhibitors of vascular smooth muscle cells

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heparan sulfates, NO, TGF-B

Front 105

neointima

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a new or thickened layer of arterial intima

Front 106

true aneurysm

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innvolves intact attenuated arterial wall or thinned ventricular wall of the heart

Front 107

what are examples of true aneurysms

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atherosclerotic, syphilitic, congenital vascular, ventricular that follow trasmural Mis

Front 108

false aneurysm

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defect in the vascular wall leading to extravascular hematoma that freely communicates with the intravascular space

Front 109

saccular aneurysm

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spherical outpouching (often contain thrombus)

Front 110

Fusiform aneurysm

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diffuse, circumferential dilation along a vascular segment (not specific for any disease or clinical manifestations)

Front 111

Marfan syndrome

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defect in fibrillin causing aberrant TGF-B activity and progressive weakening of elastic tissue

Front 112

LoeysDietz syndrome

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mutations in TGF-B receptors lead to abnormalities in collagen I and III

Front 113

Ehlers-Danlos syndrome (vascular forms)

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type III collagen mutation

Front 114

example of nutritional basis for aneurysm formation

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vit C deficiency (lack of cross-linking)

Front 115

What degrades ECM components

Back 115

MMPs

Front 116

cystic medial degeneration

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ischemia of media causing scarring, inadequate ECM synthesis, producation of GAGs

Front 117

two most important disorders that predispose to aortic aneuryms

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atherosclerosis and hypertension

Front 118

most common atherosclerosis aneurysm sites

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abdominal aorta

Front 119

most common hypertension aneurysm site

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ascending aorta

Front 120

mycotic aneurysm

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caused by infections

Front 121

why does the media become ischemic in atherosclerosis of abdominal aorta

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plaque in intima compresses on underlying media and comprises nutrient and waste diffusion from vascular lumen into arterial wall

Front 122

Major influence that leads to aneurysm formation is

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production of MMP by inflammatory cell infiltrates

Front 123

Inflammatory AAA (abdominal aortic aneurysm)

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dense periaortic fibrosis containing abundant lymphoplasmacytic inflammation with many macrophages and often giant cells (cause uncertain)

Front 124

Mycotic AAA

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lesions that become infected by lodging of microorganisms in wall

Front 125

common bacteria causing mycotic AAA

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from Salmonella gastroenteritis bateremia

Front 126

how do AAA present

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abdominal mass, often palpably pulsating, that simulates a tumor

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how quickly do aneurysms expand

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0.2-0.3 cm per year

Front 128

when should a aneurysm be managed aggresively

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greater than 5cm; surgical bypass

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signs and symptoms of thoracic aneurysm

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encroachment causing repiratory difficulties, swallowing issues, persistent cough (irritation of recurrent laryngeal nerve), pain from bone erosion, cardiac disease

Front 130

aortic dissection

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blood splays apart the laminar planes of the media to form a blood-filled channel within the aortic wall

Front 131

iatrogenic

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induced inadvertently when trying to fix problem or by diagnotic procedure

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proximal lesions in aotic dissections

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more common, involve both ascending and descending or just ascending (type I and II)

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distal lesions in aortic dissection

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doesn't involve ascending aorta, usually distal to subclavian artery (type III)

Front 134

clinical symptoms of aotic dissection

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sudden onset excruciating pain in anterior chest