Pathology 11 (Blood Vessels)

Front 1

general mechanisms for blood vessel diseases

Back 1

1) narrowing/obstruction
- gradual = atherosclerosis
- acute = thrombosis
2) weakening of wall
- dilation
- rupture

Front 2

intima

Back 2

single layer of endothelial cells and minimum connective tissue in arteries

Front 3

internal elastic lamina

Back 3

dense elastic membrane that separates arterial intima from media

Front 4

arterial media

Back 4

smooth muscle
elastic fibers in larger vessels
controlled by ANS & local metabolic factors

Front 5

external elastic lamina

Back 5

dense elastic membrane that separates the arterial media from the adventitia

Front 6

adventitia

Back 6

connective tissue that surrounds vessels

contains vasa vasorum in larger vessels

Front 7

vasa vasorum

Back 7

small arteries in the adventitia of larger vessels that nourish the outer part of the media

Front 8

what are the layers of vessels?

Back 8

from inside out:
intima
internal elastic lamina
media
external elastic lamina
adventitia

Front 9

what are the principal points of physiologic resistance to flow?

Back 9

arterioles

Front 10

where does the blood flow change from pulsatile to steady?

Back 10

arterioles

Front 11

arteriole diameter

Back 11

20-100 um

Front 12

capillary diameter

Back 12

approximate diameter of red blood cell

Front 13

capillary structure

Back 13

no media

thin basement membrane with endothelial cell lining

Front 14

what is the site of exchange between tissue and blood?

Back 14

capillaries

Front 15

why are capillaries ideal for nutrient/waste product exchange?

Back 15

they have very thin walls and slow blood flow

Front 16

post-capillary venules

Back 16

preferentially involved in inflammation

site of vascular leakage and leukocyte exudation

Front 17

veins

Back 17

larger lumen than arteries
thinner wall than arteries
less developed media
poorly defined internal elastic membrane
valves to prevent reversal of flow

Front 18

where is 2/3 of the body's blood?

Back 18

veins

Front 19

lymphatic vessels

Back 19

thin walled
endothelial lined
drainage system for returning interstitial fluid and inflammatory cells to blood
devoid of blood cells

Front 20

storage organelle for vWF

Back 20

vWF = von Willebrand Factor

Weibel-Palade bodies

Front 21

what type of cells stain positive for CD31?

Back 21

endothelial cells

Front 22

endothelial cells

Back 22

semipermeable membrane for molecule transfer
maintain non-thrombogenic surface
regulate growth of other cell types (smooth muscle)

Front 23

endothelial cell activators

Back 23

cytokines & bacterial products

hemodynamic stresses & lipid products

advanced glycosylation end products

Front 24

effect of NO on endothelial cells

Back 24

vasodilates/relaxes smooth muscle cells

Front 25

effect of endothelin on endothelial cells

Back 25

vasoconstricts/contracts smooth muscle cells

Front 26

endothelial dysfunction

Back 26

impaired vasoreactivity or induced thrombogenic surface, abnormally adhesive for inflammatory cells

Front 27

endothelial stimulation

Back 27

rapid (minutes)

independent of new protein synthesis

Front 28

endothelial activation

Back 28

delayed (hours/days)

dependent on gene expression and protein synthesis

Front 29

what is the predominant cellular element of the vascular media?

Back 29

smooth muscle cells

Front 30

what cells synthesize collagen, elastin, proteoglycans, growth factors, and cytokines in the vascular media?

Back 30

smooth muscle cells

Front 31

promoters of smooth muscle cell migration to intima and proliferation

Back 31

PDGF
FGF
IL-1
Endothelin-1
Thrombin
IFN-gamma

Front 32

inhibitors of smooth muscle cell migration to intima and proliferation

Back 32

heparan sulfates
NO
TGF-beta

Front 33

intimal thickening in response to injury

Back 33

vascular injury stimulates smooth muscle growth and formation of neointima to replace damaged endothelium (associated matrix synthesis thickens intima)

Front 34

roles of smooth muscle cells in intimal thickening

Back 34

migrate (from media or from circulating precursor cells)
proliferate
synthesize ECM
de-differentiate
- lose ability to contract
- gain ability to divide
- gain ability to make ECM
returns to nonproliferative state when endothelium restored

Front 35

three congenital anomalies in blood vessels

Back 35

berry aneurysms
arteriovenous fistulas (AVMs)
fibromuscular dysplasia

Front 36

berry aneurysms

Back 36

occur in cerebral vessels

Front 37

arteriovenous fistulas

Back 37

abnormal connections btwn arteries and veins that bypass capillaries

congenital or acquired

if large, can short-circuit blood from arterial to venous circulation -> high output cardiac failure

rupture, esp. in brain

Front 38

causes for acquired arteriovenous fistulas

Back 38

inflammation
trauma
dialysis access

Front 39

fibromuscular dysplasia

Back 39

focal irregular thickenings of walls of medium to large muscular arteries (thickened by combination of irregular medial and intimal hyperplasia and fibrosis -> luminal stenosis)

probably developmental abnormality

causes renovascular HTN
can develop aneurysms and rupture

1st degree relatives have inc. risk

Front 40

arteriosclerosis

Back 40

hardening of arteries (general term for vascular diseases that have thickening and loss of elasticity of arterial walls)
3 types:
1) atherosclerosis
2) monckeberg medial calcific sclerosis
3) arteriolosclerosis

Front 41

atherosclerosis

Back 41

primarily affects elastic arteries and lg-med muscular vessels

intimal lesions = atheromas/fibrofatty plaques protrude into lumen and/or weaken media

Front 42

monckeberg medial calcific sclerosis

Back 42

calcium deposits in medium sized muscular arteries in people over 50

usually not clinically significant

Front 43

arteriolosclerosis

Back 43

involves small arteries and arterioles

associated with HTN and diabetes

Front 44

unchangeable factors in atherosclerosis

Back 44

age
sex
genes

Front 45

influence of age on atherosclerosis

Back 45

starts in childhood; usually not evident until middle age or later (ages 40-60)
death rates rise each decade

Front 46

effect of sex on development of atherosclerosis

Back 46

in reproductive years, female ischemic heart mortality 1/5 of males

after menopause, women gradually equal and then surpass men

estrogen has protective effects

Front 47

effect of genetics on atherosclerotic development

Back 47

polygenic familial predisposition

Front 48

changeable factors in atherosclerosis development

Back 48

hyperlipidemia
hypertension
smoking
diabetes
homocysteine
hemostatic/thrombotic
C-reactive protein
Lipoprotein (a)
Type A personality
weight gain

Front 49

effect of hyperlipidemia on atherosclerotic development

Back 49

high LDL increases risk
high HDL decreases risk
- inc. by exercise, moderate EtOH
- dec. by obesity, smoking

lowering serum cholesterol reduces CV disease risk, and slows disease

Front 50

what is the function of HDL?

Back 50

mobilize cholesterol from atheromas and transport it to the liver for excretion in bile

Front 51

diseases that cause hypercholesterolemia and subsequently accelerate atherosclerosis

Back 51

diabetes
hypothyroidism

Front 52

above what level is cholesterol bad

Back 52

> 200 mg/dL

Front 53

what dietary cholesterol/fats are bad? which are good?

Back 53

bad - animal fat, egg yolks, butter, margarine (has trans-unsaturated fat)

good - fish oil with omega-3 FAs (fish shouldn't have mercury or be a farm fish)

Front 54

how do statins work?

Back 54

inhibit cholesterol synthesis in the liver by inhibiting HMG CoA reductase

Front 55

effect of HTN on atherosclerotic development

Back 55

>45, more risk than hypercholesterolemia

Front 56

what is the most important cause of left ventricular hypertrophy?

Back 56

hypertension

Front 57

effect of diabetes on development of atherosclerosis

Back 57

induces hypercholesterolemia
DM inc. incidence of MI x2
" inc. leg gangrene x100
" inc. risk of stroke

Front 58

effect of homocysteine on development of atherosclerosis

Back 58

causes endothelial dysfunction via generation of ROSs and interferes with vasodilator and antithrombogenic fcns of NO

rare inborn error of metabolism in homocystinuria causes inc. plasma levels leading to premature vascular disease

low folate or B12 levels can cause

Front 59

factors the affect the levels of CRP

Back 59

stopping smoking decreases
weight loss decreases
exercise decreases
statins decrease

measure ultra-sensitive CRP

Front 60

what are the stages in the pathogenesis of atherosclerotic plaques?

Back 60

1) endothelial injury results in endothelial dysfcn (inc. permeability, wbc adhesion, thrombotic potential)
2) accumulation of LDL and its oxidized form in vessel wall
3) monocyte adhesion, migration into intima, transformation into macrophages & foam cells
4) platelet adhesion
5) release of factors from platelets, macrophages, endothelial cells -> smooth muscle cell recruitment
6) smooth muscle proliferation and ECM production
7) lipid accumulation extracellularly and inside macrophages & smooth muscle cells

Front 61

what is the cornerstone of the response-to-injury hypothesis of atherosclerotic plaque development?

Back 61

endothelial injury resulting in endothelial dysfunction

Front 62

what are the two major determinants of endothelial dysfunction?

Back 62

1) hemodynamic disturbances (disturbed/turbulent flow induces endothelial genes with inflammatory/atherogenic activities and favors apoptosis)
2) adverse effects of hypercholesterolemia

Front 63

how do monocytes bind to endothelial cells early in atherogenesis?

Back 63

early in the process, endothelial cells start expressing VCAM-1

Front 64

what is the role of macrophages in atherogenesis?

Back 64

ingest lipoproteins, esp. oxidized LDL, which is initially protective but with progressive accumulation causes lesions to progress

make:
- IL-1 and TNF -> inc. wbc adhesion
- monocyte chemotactic protein-1 -> recruits monocytes to plaque
- toxic oxygen species -> oxidize LDL
- growth factors -> stimulate muscle proliferation

Front 65

what is the major lipid component of atherosclerotic plaques?

Back 65

cholesterol and its esters

Front 66

mechanisms of hyperlipidemic atherogenesis

Back 66

1) impairs endothelial fcn via free radical (inactivate NO and activate NF-kappaB)
2) lipoproteins accumulate at sites of inc. endothelial permeability
3) free radicals modify lipid to form oxidized LDL

Front 67

functions of oxidized LDL in atherogenesis

Back 67

easily ingested by macrophages (scavenger receptor; accumulation leads to foam cells)

chemotactic for monocytes

inhibits motility of macrophages already in lesion

cytotoxic to endothelial and smooth muscle cells

Front 68

what organisms have been found in atherosclerotic plaques but not in normal arteries?

Back 68

herpes, CMV, Chlamydia pneumoniae

suspected pathogenetic role, but not proven

higher Ab titers v. Chlamydia in pts with more severe atherosclerosis (but it is a very common infection)

Front 69

from where do smooth muscle cells migrate in atherosclerosis?

Back 69

from the media to the intima, where they proliferate and make ECM

proliferation aided by PDGF, FGF, TGF-alpha

Front 70

type I atherosclerotic lesion

Back 70

isolated macrophage foam cells

Front 71

type II atherosclerotic lesion

Back 71

fatty streak = small aggregates of lipid-laden macrophages, with extracellular lipids and T lymphs
- multiple flat yellow spots <1mm coalesce into a streak >1cm long
- flat - don't interfere with blood flow
- probable precursor of atheromatous plaque, but also found in areas not prone to plaque

can be present in aorta at <1yr, but def. present by 10 yrs

Front 72

type III atherosclerotic lesion

Back 72

intermediate lesion

Front 73

type IV-V atherosclerotic lesion

Back 73

atheromatous plaque = raised yellow-white plaque with yellow/white soft core of lipid covered by a firm, white fibrous cap
- impinges on arterial lumen (principal cause of arterial narrowing in adults)

mainly found in elastic, large and medium sized arteries (prominent around ostia of major branches)

Front 74

acute consequences of atheromas

Back 74

MI
stroke
aneurysm
peripheral vascular disease

Front 75

chronic consequences of atheromas

Back 75

chronic ischemic heart disease
ischemic encephalopathy

Front 76

microscopic appearance of atheromatous plaques

Back 76

fibrous cap of smooth muscle cells and dense collagen ECM

cellular area beneath (macrophages, smooth muscle cells, T lymphs)

deeper core of lipid material, cholesterol clefts, lipid-laden foam cells, thrombus

neovascularization at periphery

can calcify

Front 77

type VI atherosclerotic lesions

Back 77

complicated/advanced lesions

focal rupture/gross ulceration exposes thrombogenic substances, causing partial or complete thrombus and downstream embolus of underlying debris

atrophy and loss of elasticity of underlying media, with weakness and aneurysmal dilation

Front 78

hemorrhage into atherosclerotic plaques

Back 78

rupture of fibrous cap or the capillaries that vascularize the plaque

the hematoma can expand the plaque or rupture it

Front 79

hypertension (BP)

Back 79

>139 / >89

Front 80

HTN is a risk factor for....

Back 80

atherosclerosis
coronary artery disease
CVA (stroke)
cardiac hypertrophy with heart failure
aortic dissection
renal failure

Front 81

how much of the general population is hypertensive?

Back 81

25%

african americans > whites (also more vulnerable to complications)

Front 82

what are the main causes of death in untreated hypertensive patients?

Back 82

ischemic heart disease/CHF (50%)
stroke (33%)

Front 83

malignant hypertension

Back 83

>200 / >120
can occur de novo, but more often is superimposed on pre-existing HTN

5% of population
death in 1-2 years if untreated
causes renal failure & retinal hemorrhages

Front 84

causes of hypertension

Back 84

90-95% idiopathic
the rest:
- renal disease
- renovascular (narrowing of renal artery)
- adrenal causes (primary hyperaldosteronism, cushings)

Front 85

vasodilating products of kidney

Back 85

prostaglandins
kallikrein-kinin system
nitric oxide

Front 86

Liddle syndrome

Back 86

mutation in ENaC protein causing inc. tubular Na resorption via aldosterone

Front 87

hyaline arteriolosclerosis

Back 87

homogeneous, pink hyaline thickening of arterioles that causes a narrowing of lumen

caused by leakage of plasma proteins and increased ECM production

can be in elderly pts with normal BP, but is more generalized and severe in pts. with HTN; also common in diabetes

Front 88

what is the major morphologic characteristic of benign nephrosclerosis?

Back 88

hyaline arteriolosclerosis

homogeneous, pink hyaline thickening of arterioles causing a narrowing of lumen

Front 89

hyperplastic arteriolosclerosis

Back 89

onion-skin laminated concentric thickening of wall of arterioles with narrowing of lumen

caused by smooth muscle and thickened basement membrane

seen in more acute and severe HTN (characteristically in malignant HTN)

Front 90

what is the major morphologic characteristic of necrotizing arteriolitis?

Back 90

hyperplastic arteriolosclerosis

Front 91

secondary HTN

Back 91

renovascular HTN - renal artery stenosis or fibromuscular dysplasia

primary hyperaldosteronism
cushing disease/syndrome
pheochromocytoma

Front 92

aneurysm

Back 92

localized abnormal dilation of an artery

most common in aorta and heart

Front 93

true aneurysm

Back 93

complete, but often attenuated arterial wall (all 3 wall layers, or attenuated wall of the heart)

can be congenital, atherosclerotic, syphilitic

Front 94

false aneurysm

Back 94

aka pseudoaneurysm

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

vascular wall is breached, but has an external wall of outer arterial layers/perivascular tissue/blood clot

Front 95

causes of aneurysms

Back 95

congenital - berry aneurysms in CNS

Infection = mycotic aneurysm
- embolization of septic focus, esp. infective endocarditis
- extension from adjacent suppurative focus
- circulating organisms directly infecting vessel wall

vasculitides

trauma

Front 96

marfan syndrome

Back 96

defective fibrillin synthesis
- aberrant TGF-beta activity
- progresive weakening of elastic tissue
- remodeling of inelastic media

Front 97

loeys-dietz syndrome

Back 97

mutated TGF-beta receptors
abnormal elastin, collagens I & II

**aneurysms can rupture even if very small**

Front 98

Ehlers-Danlos vascular type

Back 98

defective collagen III synthesis

Front 99

Vitamin C deficiency

Back 99

defective collagen cross-linking

Front 100

general pathogenesis of aneurysms

Back 100

1) poor intrinsic quality of vessel wall connective tissue
2) altered balance in collagen synthesis/degradation by localized inflammation and resultant proteolytic enzyme production
3) loss of smooth muscle or inappropriate synthesis of noncollagenous or non-elastic ECM

Front 101

how can collagen synthesis/degradation be altered in aneurysm formation?

Back 101

inc. matrix metalloproteinase production, esp. by macrophages in atherosclerosis or vasculitis

dec. in tissue inhibitor of metalloproteinase (TIMP) expression

Front 102

cystic medial degeneration

Back 102

scarring, loss of elastic fibers, dec. ECM synthesis, and inc. amorphous (glycosaminoglycan) production caused by ischemia

Front 103

how does intimal thickening cause necrosis?

Back 103

increases distance nutrients/waste products must diffuse to/from inner media

Front 104

saccular aneurysm

Back 104

spherical

5-20 cm

involves only a portion of arterial wall

often partially or completely filled with thrombus

Front 105

fusiform aneurysm

Back 105

gradual, progressive dilation of complete circumference of artery

up to 20 cm diameter

may involve large lengths of aorta

Front 106

pathogenesis of atherosclerotic abdominal aortic aneurysms

Back 106

major influence is MMP production -> degrades collagen and ECM

intimal thickening -> longer diffusion distance for nutrients/waste products -> medial degeneration and necrosis

Front 107

risk factors for atherosclerotic abdominal aortic aneurysm

Back 107

male > female
> 50 yo
smoking