Heart - Dr. Nowacki Atherosclerosis Lecture I

Front 1

List the pathology and diseases that occur secondary to luminal narrowing/obstruction

Back 1

Atherosclerosis, thrombosis, emboli

Front 2

List the pathology and dz that occur secondary to weakening of the vessel walls

Back 2

Dilation, dissection, rupture

Front 3

List the 5 important pathological processes of blood vessesl

Back 3

1. Athersclerosis (most important according to Nowacki)
2. Vasculitis (div by type)
3. Aneurysms
4. Diseases of Veins
5. Blood vessel neoplasms

Front 4

what are the vessel layers

Back 4

Intima, internal elastic lamina, media, external elastic lamina, adventitia

Front 5

how does arterial wall thickness change as vessels become smaller

Back 5

wall thickness decreases but the ratio of thickness to lumen diameter increases

Front 6

how are vessels classified according to size

Back 6

large = elastic
medium = muscular
small = <2 mm
arterioles = 20-100 micrometers
capillaries = 7-8 microns

Front 7

which vessel is the principle point of physiologic resistance

Back 7

arterioles
**important point of involvment in HTN

Front 8

what is the relationship between diameter and resistance

Back 8

la place's law --> wall tension is proportional to diameter and internal pressure in lumen

as diameter decreases by 1/2, resistance increases by 16

Front 9

what is the vasa vasorum and where is it found?

Back 9

small vessels to supply the outer portion of media in large vessles

* important in syphillis

Front 10

where are the nerves found?

Back 10

in the adventitia

Front 11

what is the difference between between capillaries and arterioles

Back 11

1.size
2.capillaries have endothelium cell lining as well, but lack media.
3.capillaries have a larger cross section and thinner walls to give a slower flow and rapid diffusion

fact from notes: capillaries allow for rapid exchange and diffusion from vessels to tissue and vice versa

Front 12

what are the two types of capillaries

Back 12

continuous and fenestrated

Front 13

where are capillaries most dense

Back 13

in metabolically active tissue (ie heart)

Front 14

what size vessels are most affected by HTN

Back 14

arterioles

Front 15

what size vessles are most affected by Atherosclerosis

Back 15

large arteries

Front 16

what does ectasia mean

Back 16

vascular dilation, +/- tortuosity

Front 17

where does vascular leakage and leukocyte excudation (inflammation escape vessels) occur

Back 17

post capillary venules

Front 18

why are venules, veins, and lymphatics more subject to injury and invasion by cancer

Back 18

because they are thinner, less organized, and there is less structure

Front 19

list the layers of the large veins, medium veins, venules, post capillary venules

Back 19

They all have an intima, media, and adventitia

Front 20

what is present in the large and muscular arteries that is not present in the arterioles and capilaries

Back 20

elastic lamina

Front 21

what surrounds the capillary endothelium

Back 21

pericytes

Front 22

Due to the poor support of veins, list three things they are predisposed to

Back 22

veins are predisposed to 1.irregular dilation 2.compression
3.easy penetration by tumors and inflammatory processes

Front 23

Lymphatics are thin, endothelial lined channels that drain interstial fluid and inflammatory cells back to the blood.

Back 23

Lymphatics constitute an important pathway for disease dissemination through transport of bacteria and tumor cells to distant sites.

Front 24

List the congenital vascular abnormalities

Back 24

1. Congenital Heart Disease
2. AV fistulas
3. Developmental or Berry Aneurysms
4. Fibromuscular Dysplasias (renal artery dysplasia

Front 25

AV Fistulas

Back 25

They occur most commonly as developmental defects but can also result from rupture of an arterial aneurysm into an adjacent vein, from penetrating injuries that pierce arteries and veins, or from inflammatory necrosis of adjacent vessels; intentionally created arteriovenous fistulas are used to provide vascular access for chronic hemodialysis. Like berry aneurysms, ruptured arteriovenous fistulas can be an important cause of intracerebral hemorrhage.7 Large or extensive arteriovenous fistulas become clinically significant by shunting blood from the arterial to the venous circulations and forcing the heart to pump additional volume; high-output cardiac failure can ensue.

Front 26

Berry Aneurysms

Back 26

occur in cerebral vessels; when ruptured these can be causes of fatal intracerebral hemorrhage

Front 27

Fibromuscular Dysplasias

Back 27

focal irregular thickening of the walls of medium and large muscular arteries, including renal, carotid, splanchnic, and vertebral vessels. The cause is unknown but is probably developmental; first-degree relatives of affected individuals have an increased incidence. Segments of the vessel wall are focally thickened by a combination of irregular medial and intimal hyperplasia and fibrosis; this results in luminal stenosis, and in the renal arteries may be a cause of renovascular hypertension Vascular outpouchings (aneurysms) may develop in the vessel segments with attenuated media and in some cases can rupture. Fibromuscular dysplasia can manifest at any age, although it is seen most frequently in young women; there is no association with use of oral contraceptives or abnormalities of sex hormone expression

Front 28

From Table 11- 1 (stated this table isn't important, but it is for test taking -- i guess meanign boards so i included it)

Elaboration of anticoagulant, antithrombotic, fibrinolytic regulators

Back 28

prostacyclin
thrombomodulin
heparin- like molecules
plasminogen activator

Front 29

table 11-1 elaboration of prothrombotic molecules

Back 29

vWF
tissue factor
plasminogen activator inhibitor

Front 30

table 11-1 modulation of blood flow and vascular reactivitiy

Back 30

vasoconstrictors; endothelin and ACE

vasodilators: NO, prostacyclin

Front 31

table 11-1 Regulation of inflmmation and immunity

Back 31

IL-1, IL-6, chemokines
adhesion molecules, VCAM -1, ICAM, E-selectin, P-selectin
histocompatibility antigens

Front 32

table 11-1 regulation of cell growth

Back 32

stimulators: PDGF, CSF, FGF

inhibitors: heparin, TGF-B

Front 33

from table 11-1 other things that maintain the permeability barrier

Back 33

oxidation of LDL

extracellular matrix production (collagen and proteoglycans)

Front 34

table 11-2 for review

Back 34

list the causes of endothelial dysfunction

Hint 34

turbulent flow, HTN, cytokines, complement, bacterial products, lipid products, advanced glycation end products, hypoxia, acidosis, viruses, cigarette smoke

Front 35

compare the amount of blood in the veins vs the arteries

Back 35

2/3 of the blood is contained in the veins

Front 36

where is vWF stored

Back 36

in weibel-palade bodies (membrane bound storage organelles) in endothelial cells

Front 37

what immunohistochemical stains ID endothelial cells

Back 37

CD31, CD34(PECAM1), factor VIII and vWF

Front 38

what factors promote vascular smooth muscle cell growht

Back 38

PDGF, endothelin-1, thrombin, FGF, INF-gamma, IL-1, vascular injury, endothelial cell dysfunction or loss

Front 39

what factors inhibit vascular smooth muscle cell growth

Back 39

heparin sulfates, NO, TGF-B

Front 40

Vasoconstrictors

Back 40

endothelin, angiotensin II, catecholamines, alpha adrenergic factors, thromboxane, leukotrienes

Front 41

vasodilators

Back 41

NO, kinins, prostaglandins, natriuretic peptides, beta adrenergics factors

Front 42

what deactivates NO

Back 42

free radicals produced by macrophages and endothelial cells (also cause oxidation of LDL)

Front 43

what are the 5 functions of vascular smooth muscle cell

Back 43

1. vasoconstrict
2. vasodilation
3. make extracellular matrix proteins
4. make growth factors and cytokines
5. can migrate and proliferate

Front 44

vascular injury = smooth muscle stimulation and growth

describe the healing process

Back 44

1. smooth muscle cells migrate to the intima, loose the ability to contract, and gain ability to divide

2. smooth muscle cell mitosis

3. elaboration of extracellular matrix

** results in intimal thickening-->will duplicate and triplicate the internal elastic lamina until there is no lumen

Front 45

what are the functions of the contractile phenotype of the vascular smooth muscle

Back 45

vasoconstriction/dilation

Front 46

what are the functions of the profliferative/synthetic pheontype

Back 46

connective tissue proteins, growth factors, cytokines

- blood vessel repair and atherosclerosis

Front 47

what are the 3 patterns of arteriosclerosis

Back 47

1. atherosclerosis
2. monckeberg medial calcific sclerosis
3.arteriolosclerosis

Front 48

define arteriosclerosis

Back 48

thickening and loss of elasticity of arterial walls

Front 49

Describe atherosclerosis

Back 49

*most frequent and most important

*slowly progressive dz of intima of large to medium sized muscular and large elastic arteries

* atheromatous plaques that protrude into and obstruct vessel lumen
*weakend media due to loss of internal and external elastic membrane

Front 50

Descending order of frequency in atheroslerosis

Back 50

abdominal aorta > coronary arteries > descending thoracic aorta > internal carotid arteries > circle of willis

Front 51

characterize and atheroma

Back 51

a fibrofatty plaque that protrudes into and obstructs vascular lumens along with weakening of the underlying media

Front 52

Other random facts about atherosclerosis from notes

Back 52

- accounts for 1/2 deaths in western countries (MI, Stroke, PVD, aneurysms)

- asymptomatic for long time
- can be completely or partially obstructed --> for the heart takes approx 70% to be affected

-clot or hemorrhage lead to MI

Front 53

what is this a picture of

Back 53

describe the typical findings

Hint 53

- calcific deposits in muscular arteries in people >50.
-may be seen on xray or palpated
**no significant clinical sequelae
-muscle is replace by Ca, media and elastic are fine.
-does not encase the entire artery (different than atherosclerosis)

Front 54

describe this pathology

Back 54

this is hyaline arteriosclerosis, what are the characteristics

Hint 54

pink homogenized thickening with vessel lumen (hyalinized, no cells) narrowing in elderly (+/- HTN) and in diabetics (microangiopathy)

Front 55

describe the pathology

Back 55

this is hyperplastic arteriolosclerosis, describe its characteristics

Hint 55

onion skin concentric thickening with narrowing of the vessel lumen, seen in really high HTN (malignant)

Front 56

describe the natural history of atherosclerosis after reviewing this image

Back 56

normal vessel-->fatty streak-->fibrofatty plaque-->advanced vulnerable plaque

Now describe the clinical phases of the vulnerable plaque

Hint 56

1. mural thrombosis, embolization, and wall weakening -->aneurysm and rupture = hemorrhagic stroke

2. plaque rupture, plaque erosion, plaque hemorrhage, mrual thrombosis, emoblization-->occlusion by thrombus = MI, stroke

3. progressive plaque growth -->critical stenosis = claudation, angina

Front 57

Describe fatty streaks; when does it first appear, where does it develop, is it related to atheroclerosis

Back 57

1. is is the earliest atherosclerotic lesion --> appear in all children by age 10

2. often occur in vascular regions that later in life DONT develop atheromas

3. may be related somehow but true relationship not yet defined

Front 58

name the common complications of atherosclerosis

Back 58

MI, stroke, aortic aneurysms, PVD, diminished arterial perfusion, mesenteric occlusion(60, 70 yo), chronic ischemic heart dz

Front 59

describe the morphology

Back 59

raised white, yellow intimal based lesion with prominence around ostia of majro branches,

picture in upper R has the fat stain added, see fattty streak around origin

image in lower R demonstrates fatty plaque with intimal macrophage derived foam cells

Front 60

describe the plaque composition

Back 60

superficial fibrous cap (sm mus, leukocytes, dense CT ECM, collagen, elastin, proteoglycans, neovasculization)

necrotic lipid laden core (cell debri, foam cells, cholesterol clefts &/or crystals, dead cells, calcium)

periphery has neovasculization

*often undergo calcification

Front 61

Figure 11-12 Gross views of atherosclerosis in the aorta. A, Mild atherosclerosis composed of fibrous plaques, one of which is denoted by the arrow. B, Severe disease with diffuse and complicated lesions (with plaque rupture and superimposed thrombosis), some of which have coalesced.

Back 61

A and C are included :

Histologic features of atheromatous plaque in the coronary artery. A, Overall architecture demonstrating fibrous cap (F) and a central necrotic (largely lipid) core (C). The lumen (L) has been moderately compromised. Note that a segment of the wall is free of plaque (arrow); the lesion is therefore "eccentric". In this section, collagen has been stained blue (Masson's trichrome stain). B, Higher power photograph of a section of the plaque shown in A, stained for elastin (black), demonstrating that the internal and external elastic membranes are attenuated and the media of the artery is thinned under the most advanced plaque (arrow). C, Higher magnification photomicrograph at the junction of the fibrous cap and core, showing scattered inflammatory cells, calcification (arrowhead) and neovascularization (small arrows).

Front 62

Right: thrombus can rapidly progress to full occlusion

Left: Calcium can overtime turn into bone

Back 62

more atherosclerosis slides

Front 63

AHA Classification

Back 63

review to the level you think will be good for the test

Front 64

describe type II lesions

Back 64

- fatty streak that is not raised, 1mm to 1 cm, and includes intracellular lipid accumulations and T lymphocytes

-occur at sites that are (and are not) susceptible to atheroma formation

Front 65

what levels of vessels are affected by plaques

Back 65

elastic - aorta, iliac, carotid

muscular - coronary, popliteal

Front 66

what events lead to advancement of plaque

Back 66

cell death, inflammation, plaque growth, remodeling of plaque, organization of thrombus, calcification

Front 67

what events lead to fatty streaks & stable plaques (ie early natural history)

Back 67

endothelial dysfunction, monocyte adhesion, SMC migration, SMC proliferation, ECM elaboration, & lipid accumulation

Front 68

what are the four modifiable risk factors for atherosclerosis

Back 68

1. hyperlipidemia - diet
2. hypertension - decrease salt intake, Rx
3. cigarette smoking - QUIT!
4. diabetes

Front 69

what are the 4 non-modifiable risk factors for atherosclerosis

Back 69

age
male gender (until women are post menopausal)
family hx
genetic abnormalities

Front 70

Other random risks of atherosclerosis

Back 70

obesity, type a personality, alcohol, LP(a), post menopausal estrogen deficiency, high carb intake, physical inactivity, chlamydia pneumoniae, increased serum homocysteine

Front 71

what type of infections may predispose to atherosclerosis

Back 71

chlamydia pneumonia and CMV (because they infect the endothelial cell)

Front 72

which cholesterol is associated with increased risk of atherosclerosis

Back 72

LDL (delivers cholesterol to peripheral tissues)

Front 73

what is the most important factor in atherosclerosis

Back 73

hypercholesterolemia --> less than 150mg/dl =low risk

Front 74

why is HDL a good cholesterol

Back 74

it mobilizes cholesterol from the existing atheroma and transports it to the liver for excretion in bile

-random drug mentioned Gemfibrozil (sp?) - reduces triglycerides and increases amt cholesterol carried in HDL

Front 75

what 3 things raise HDL

Back 75

exercize, moderate alcohol, weight loss, QUIT smoking

Front 76

how do statins lower cholesterol

Back 76

by inhibiting HMGCoA reductase (req for cholesterol synth in liver)

Front 77

what inborn error in metabolism predisposes to vascular dz

Back 77

homocysteinuria (high levels of homocysteine > 100umol/L

Front 78

what dietary defect can cause homocysteinuria

Back 78

low folate and vit B12 intake

Front 79

what cirulating markers are predictors of athero risk

Back 79

plasminogen activator inhibitor-1 (PAI-1), CRP, lipoprotein a (LPa)

Front 80

how does lipoprotein a LPa differ from LDL

Back 80

lp(a) contains apolipoprotein B-100 of LDL linked to apo-A

Front 81

what type of flow may lead to endothelial dysfunction

Back 81

turbulent flow with low shear stress

Front 82

what binds t cells and monocytes to cause formation of atheroma

Back 82

VCAM-1

Front 83

what do macrophages produce that increases adherance of WBCs

Back 83

IL-1 and TNF

Front 84

what defect is present in homozygous familial hypercholesterolemia

Back 84

defects in the LDL receptor

resulting in decreased hepatic uptake and increased circulating LDL - LDL 5-10 X normal =severe atherosclerosis in childhood

these patients may have MI before age of 20

Front 85

describe heterozygoes for familial hypercholesterolemia

Back 85

LDL cholesterol 2-3X normal, decreases hepatic uptake of LDL/IDL and premature atherosclerosis, Xanthomas

Front 86

Hyperlipoproteinemias

Type IIa

Back 86

High Chol HIgh LDL

defect: LDL rec or Apolipoprot E

Front 87

Hyperlipoproteinemias

Type IIb

Back 87

High Chol&Triglyceridesm High LDL & VLDL

defect: LDL rec or Apolipoprot B

Front 88

Hyperlipoproteinemias

Type IV

Back 88

High Triglycerides High VLDL

Defect: lipoprotein lipase

Front 89

Describe the response to Injury Hypothesis

Back 89

Atherosclerosis is a chronic inflamatory response of the arterial wall initiated by injury to the endothelium. Lesion progression is sustained by interaction between modified lipoprotiens, monocyte derived macrophages, T lymphocytes, and normal cellular constituents of the arterial wall

Front 90

Describe the pathogenesis and progression to plaque formation

Back 90

chronic endothelial injury--> lipoprot (LDL/VLDL) & lipids gain entry into vessel wall and acculuate (right under endothelium)--> monocytes and platelets attach, mono's migrate into intima and transform inot macro and then foam cells--> migration and prolif of SMCs--> ongoing lipid accumulation and growth of plaque -->creates a bump in vessel wall --> creates more turbulence--> back to begining again with more endothelial injury

Front 91

what are the causes of endothelial injury

Back 91

hyperlipidemia
smoking
hypertension
immune attack
distrubed flow (turbulence)
toxins

**Injury more prone at sites with turbulent blood flow