Vascular Anomalies, HTN, Atherosclerosis, Aneurysms/Dissections

Question 1

3 concentric histologic layers of blood vessels

Answer 1

Intima (single layer of endothelial cells)

Media (well organized in arteries, haphazard in veins)

Adventitia (external to media, often separated from it by wide external elastic lamina)

Question 2

Describe media component in elastic arteries

Answer 2

High elastin content — allows expansion during systole, recoil during diastole —> propels blood toward organs

Question 3

What changes occur in the media component of elastic arteries with age?

Answer 3

Becomes less compliant with increasing age —> increased systolic BP

Question 4

Describe media component in muscular arteries

Answer 4

Circumfirentially oriented smooth muscle; arteriolar smooth muscle contraction = vasoconstriction, or relaxation = vasodilation

Question 5

______ are the principle point of physiologic resistance to blood flow — wherein resistance to fluid flow is inversely proportional to the fourth power of the diameter

Answer 5

Arterioles

[Small changes in vasoconstriction at this level has profound effects on BP]

Question 6

Small arterioles that supply O2 to the outer media of large arteries

Answer 6

Vaso vasorum

Question 7

Most inflammatory reactions affect what type of blood vessel?

Answer 7

Veins — leads to vascular leakage and leukocyte exudation

Question 8

Describe architecture of veins

Answer 8

Larger lumens, thinner and less organized walls

Less rigid = susceptible to dilation and compresion, as well as infiltration by tumors and inflammatory processes

Question 9

Reverse flow d/t gravity is prevented in the extremities by ____ ____

Answer 9

Venous valves

Question 10

Describe architecture and function of lymphatic vessels

Answer 10

Thin walled, lined by specialized endothelium

Return intestinal fluid and inflammatory cells to the bloodstream

Transport bacteria etc. and tumor cells, making them a pathway for disease dissemination

Question 11

Blood pressure control occurs at the level of the _______

Gas and nutrient exchange occur at the level of the _____

Answer 11

Arteriole

Capillary

Question 12

ADPKD is associated with what type of vascular anomaly?

Answer 12

Berry aneurysm (circle of willis)

Question 13

Anomaly characterized by abnormal connection between arteries and veins; in other words, capillaries are not present

Answer 13

Arteriovenous malformations (AVM)

Question 14

Large or multiple AVMs may shunt blood from arterial to venous circulation, forcing the heart to pump additional volume leading to ______

Answer 14

High-output cardiac failure

Question 15

Focal irregular thickening in medium and large musclar arteries, including renal, carotid, splanchnic, and/or vertebral vessels

Answer 15

Fibromuscular dysplasia

Question 16

With fibromuscular dysplasia, first degree relatives have an increased incidence, as do young _____.

Medial and intimal hyperplasia leads to _____ _____

This condition displays on angiography as ___________-appearing due to marked attenuation of adjacent media

One of the major complications is development of an ______

Answer 16

Women

Luminal stenosis

“String of beads”

Aneurysm

Question 17

Fibromuscular dysplasia of renal arteries leads to what complication?

Answer 17

Renovascular HTN

Question 18

Cell type that creates nonthrombogenic surface, maintaining blood in fluid state and modulating the medial smooth muscle tone, metabolizing hormones (angiotensin), regulating inflammation, and affecting growth of other cell types (especially muscle cells)

Answer 18

Endothelial cells

[note that endothelial dysfunction results in proinflammatory and prothrombogenic state, resulting in thrombus formation, atherosclerosis, and vascular lesions of HTN]

Question 19

Describe vascular smooth muscle cells

Answer 19

Ability to proliferate (can be maladaptive)

Synthesize collagen, elastin, and proteoglycans

Elaborate growth factors and cytokines

Vasoconstriction and/or dilation

Question 20

Stereotypical response of a vessel wall to ANY insult

Answer 20

Intimal thickening

[associated with endothelial cell dysfunction or loss; stimualtes sm m cell recruitment and proliferation and associated matrix synthesis]

Question 21

Neointimal sm m cells are motile, undergo cell division, and acquire new biosynthetic capabilities

T/F: smooth muscle cells can not return to nonproliferative state even if endothelial layer is normalized

Answer 21

False — these cells CAN return to nonproliferative state with normalization of endothelial layer (a change that may take place with lifestyle modifications, medication, etc.)

However, the healing response can result in intimal thickening that may impede blood flow

Question 22

What is the initial event following vascular injury?

Answer 22

Endothelial cell activation!

Insults d/t turbulent flow, HTN, cytokines, complement, bacterial products, lipid products, hypoxia, acidosis, viruses, cig smoke, etc. —> increased expression of PROCOAGULANTS, ADHESION MOLECULES, and proinflammatory factors as well as altered expression of chemokines, cytokines, and GROWTH FACTORS signify “activated state”

Question 23

Response to vascular injury:

1. Recruitment of smooth muscle cells or smooth muscle precursor cells to the _____
2. Smooth muscle cell _____
3. Elaboration of ______

Answer 23

Intima

Mitosis

ECM (thrombogenic!)

Question 24

Definition of hypertensive vascular disease as it relates to increased risk of atherosclerosis

Answer 24

Sustained systolic > 139 mmHg, or sustained diastolic >89 mmHg associated with increased risk of atherosclerosis

Question 25

Causes of secondary HTN

Answer 25

Primary aldosteronism, Cushing syndrome, or pheochromocytoma [other causes — renal disease, exogenous hormones, acromegaly, thyroid conditions, pregnancy, coarctation of aorta, polyarteritis nodosa, psychogenic, sleep apnea, acute stress, increased ICP]

Question 26

HTN secondary to __________ is caused by increased production of renin from the ischemic kidney. A _____ can be heard on auscultation of the affected kidneys

Answer 26

Renal artery stenosis Bruit

Question 27

What pt populations are at increased risk of essential (primary) HTN? What are some complications?

Answer 27

Risk factors: increasing age, African Americans have higher prevalence Complications: cardiac hypertrophy and heart failure, multi-infarct dementia, renal failure 50% of untreated HTN pts die of ischemic heart disease (IHD) or CHF; another 1/3 die of stroke

Question 28

Signs and symptoms of malignant HTN

Answer 28

Systolic > 200 mmHg, diastolic > 120 mmHg Severe HTN, renal failure, retinal hemorrhages and exudates, +/- papilledema; often superimposed on pre-existing benign HTN Untreated leads to death within 1-2 years

Question 29

BP is a function of what 2 physiologic processes?

Answer 29

Cardiac output — HR and stroke volume (strong influence by blood volume — relationship with renal sodium excretion vs. reabsorption) Peripheral vascular resistance — regulated at level of arterioles; influenced by neural and hormonal inputs

Question 30

Humoral and neural factors that cause constriction in peripheral vessels

Answer 30

``` Humoral: Angiotensin II Catecholamines Thromboxane Leukotrienes Endothelin ``` Neural: Alpha-adrenergic

Question 31

Humoral and neural factors that cause dilation in peripheral vessels

Answer 31

Humoral: Prostaglandins Kinins NO Dilators: Beta-adrenergic

Question 32

The volume expansion resulting from activation of the RAAS induces myocardial release of ______, leading to Na+ excretion and diuresis as well as vasodilation - thus lowering BP

Answer 32

ANP

Question 33

What condition in the kidney might result in RAAS activation and ANP release?

Answer 33

Renal artery stenosis

Question 34

Compare/contrast the 2 forms of small blood vessel disease result from HTN

Answer 34

Hyaline arteriolosclerosis — homogenous pink (hyaline) thickening of the vessel wall, with associated luminal narrowing Hyperplastic arteriolosclerosis — occurs in SEVERE HTN, smooth muscle cells form concentric lamellations (“onion skinning”) with resultant luminal narrowing

Question 35

What condition tends to occur in those >50 y/o and is characterized by calcification of muscular arteries, involving internal elastic membrane, but there is NO narrowing of the lumen, and thus NO clinical significance?

Answer 35

Monckeberg medial sclerosis

Question 36

Raised lesion with a soft grumous core of lipid covered by a fibrous cap

Answer 36

Atheroma = atheromatous = atherosclerotic plaque [used interchangeably]

Question 37

Why are premenopausal women somewhat protected from atherosclerosis?

Answer 37

Atheroprotective effects of estrogen

Question 38

Major risk factor for atherosclerosis that is sufficient to initiate atheroma development even in the absence of other factors

Answer 38

Hypercholesterolemia

Question 39

How does metabolic syndrome contribute to atherosclerosis risk?

Answer 39

Insulin resistance, HTN, dyslipidemia, hypercoagulability, and proinflammatory state may contribute to endothelial dysfunction and/or thrombosis

Question 40

What serum marker may be used to predict cardiovascular risk?

Answer 40

C reactive protein (CRP)

Question 41

Atherosclerosis does not occur randomly in vessels, nor does it occur everywhere uniformly. Where do most lesions tend to occur and why?

Answer 41

Most lesions tend to occur at opening of exiting vessels, branch points, posterior abdominal aorta, etc. — due to HEMODYNAMIC TURBULENCE and other flow disturbances in these locations

Question 42

Lipids in atheromatous plaques are predominantly cholesterol and cholesterol esters; they accumulate in the _____, are taken up by macrophages and partially oxidized. This modified LDL further accumulates in macrophages and ______ cells, forming _____ cells and a lesion known as a “fatty streak”. this stimulates an inflammatory response to accumulation of this toxic form of LDL

Answer 42

Intima Smooth muscle; foam

Question 43

As part of the pathogenesis of atherosclerosis, accumulatioin of cholesterol crystals within macrophages is recognized by the inflammasome, which leads to ____ secretion. More macrophages and ______ are recruited and activated. Inflammatory cytokines further activate endothelial cells, and growth factors stimulate smooth muscle cells to migrate to the intima and proliferate.

Answer 43

IL-1; T-lymphocytes

Question 44

Several growth factors are implicated in smooth muscle proliferation. What are some examples?

Answer 44

PDGF (released by locally adherent platelets) Fibroblast growth factor TGF-alpha

Question 45

Once there is initial formation of an atheromatous plaque, the soft fibrofatty structure becomes covered with a fibrous cap (dense collagen fibers). The center of the plaque is _______, containing lipid, debris, foam cells, and thrombus, surrounded by a zone of inflammatory and smooth muscle cells

Answer 45

Necrotic

Question 46

Common sites of atherosclerosis involvement

Answer 46

[in decreasing order of frequency]: ``` Abdominal aorta Coronary arteries Popliteal arteries Internal carotid arteries Circle of willis ```

Question 47

Complications of atherosclerotic plaques

Answer 47

Rupture and ulceration — may lead to thrombosis Hemorrhage — may follow plaque rupture Embolism — may follow plaque rupture Aneurysm formation

Question 48

One of the consequences of atherosclerosis is gradual shrinkage of vessel lumen, eventually leading to ischemia downstream. At a point known as _____ _____, approximately 70% of the vessel is occluded which may lead to chronic ischemia of myocardium, bowel, brain, the extremities, etc.

Answer 48

Critical stenosis

Question 49

What are some characteristics of atheromatous plaques that are more prone to rupture?

Answer 49

Those in which the fibrous cap is continually being remodeled Those with increased inflammation — which can accelerate cap degradation and inhibit its resynthesis, thus reducing the amount of collagen in the cap and weakening it Physical stresses can cause plaque rupture — like changes in BP, vasoconstriction, etc.

Question 50

T/F: there is a direct relationship between plaque thickness and likelihood of rupture

Answer 50

True — the thicker the plaque, the more vulnerable it is to rupture

Question 51

What is the difference between true vs. false aneurysm?

Answer 51

True aneurysm = an intact (but thinned) muscular wall at the site of dilation False aneurysm = defect through the wall of the vessel, communicating with an extravascular hematoma

Question 52

What connective tissue disorder is associated with increased risk of aneurysm formation?

Answer 52

Marfan syndrome — defective fibrillin synthesis

Question 53

Conditions in which there is net degradation of vascular wall CT can predispose pts to aneurysms, this includes inflammatory conditions like atherosclerosis, which result in increased ________

Answer 53

Matrix metalloprotease

Question 54

What are some conditions that predispose to aneurysm by weakening the vascular wall by ischemia?

Answer 54

Atherosclerosis —> ischemia of inner media HTN —> ischemia of outer media Tertiary syphilis —> ischemia of outer media (thoracic aorta)

Question 55

How does tertiary syphilis contribute to ischemia of the outer media (particularly in thoracic aorta)

Answer 55

Obliterative endarteritis (characteristic of late-stage syphilis) shows a predilection for small vessels, including those of the vasa vasorum of the thoracic aorta This leads to ischemic injury of the aortic media and aneurysmal dilation which sometimes involves the aortic valve annulus (aortic valve regurgitation) — sometimes referred to as “tree barking”

Question 56

During pathogenesis of aneurysms, loss of vascular wall elastic tissue, or ineffective elastin synthesis leads to cystic medial degeneration, with disrupted and disorganized elastin filaments and increased ground substance (proteoglycans). Cystic medial degeneration is a final common result of different conditions, including ischemic medial damage and _____ syndrome. However, the 2 MOST IMPORTANT causes of aortic aneurysms are ______ and ______

Answer 56

Marfan Atherosclerosis; HTN

Question 57

Where do mycotic aneurysms originate from? (multiple)

Answer 57

Septic emboli (usually complication of infective endocarditis) Extension of an adjacent suppurative process Circulating organisms directly infecting the arterial wall

Question 58

AAAs are characterized by severe _______ of the aorta, covered with mural thrombus. They may be detected as a _________ mass in the abdomen

Answer 58

Atherosclerosis; pulsating

Question 59

AAAs occur in the abdominal aorta, usually below the _____ arteries and often involve the _______ arteries

Answer 59

Renal; common iliac

Question 60

Complications of AAA

Answer 60

Rupture and hemorrhage Occlusion of branching arteries and downstream ischemia Embolism Impingement on another structure

Question 61

AAA rupture risk is related to aneurysm ______

Answer 61

Size! — aneurysms 5cm or greater are usually managed surgically

Question 62

Thoracic aortic aneurysms are often d/t _____, or less commonly congenital defects in CT: Marfan syndrome. Marfan is a _____ inherited disorder resulting in defective synthesis of fibrillin (FBN1), leading to aberrant ______ activity that weakens elastic tissue

Answer 62

HTN AD TGF-B

Question 63

Clinical presentation of thoracic aortic aneurysm

Answer 63

Clinical presentation is often d/t impingement of: lower respiratory tree, esophagus, recurrent laryngeal nn Aortic valvular insufficiency Rupture

Question 64

Complication of aortic aneurysm in which blood enters a defect in the intima and travels through a tissue plane within layers of the aortic media Who is most at risk for this complication?

Answer 64

Aortic Dissection Most commonly occurs in hypertensive males age 40-60, or younger patients with Marfans [primary risk factor is HTN]

Question 65

Classic presentation of aortic dissection

Answer 65

Sudden onset of severe chest pain (usually beginning in anterior chest), radiating to the back between the scapulae, and moving downward as the dissection progresses —can be confused with AMI!

Question 66

What is a “double-barreled aorta”?

Answer 66

If dissecting aorta hematoma re-enters the lumen of the aorta through a second distal intimal tear, a new false vascular channel is created — creating appearance of double-barreled aorta This averts a fatal extraaortic hemorrhage, and over time, such false channels can be endothelialized to become recognizable chronic dissections

Question 67

With aortic dissection, blood enters aortic wall via an intimal tear (cause is generally unknown), forming an intramural hematoma. Usually in hypertensive patients, there is some degree of cystic medial degeneration. Where do most aortic dissections arise?

Answer 67

Most arise in the ascending aorta, within 10 cm of the aortic valve

Question 68

Aortic dissections can rupture through the _______ leading to massive hemorrhage or _____ ______ (hemorrhage into pericardial sac)

Answer 68

Adventitia; cardiac tamponade

Question 69

Classifications of aortic dissections and which are more common

Answer 69

Type A = DeBakey I and Debakey II Type B = DeBakey III Type A dissections (involving the ascending aorta) are more common and associated wtih higher morbidity and mortality. They are treated with antihypertensive therapy and an attempt to surgically repair the intimal tear