Chapter 10 blood vessels

Question 1

vascular disease develops through 2 principal mechanisms, what are they?

Answer 1

• narrowing or complete obstruction of vessel lumina, (either progressively by atherosclerosis or acutely by thrombosis or embolism
• Weakening of vessel walls, causing dilation and/or rupture.

Question 2

what are the 3 layers of the vessel wall?

Answer 2

intima, media and adventitia.

Question 3

why is laminar flow important for endothelial cells?

Answer 3

to maintain non-thrombogenic endothelial lining. Vascular endothelial growth factor (VEGF) and firm adhesion to the underlying basement membrane. Trauma/injury results in denude vessel walls of the endothelial cells that tip the scales towards thrombosis and vasoconstrciton.
Endothelial cells also respond to various physiological and pathologic stimuli by modulating their usual (consitiutive) functions and by expressing new (inducible) properties (endothelial activation). INDUCERS such as: bacterial products, cytokines, hemodynamic stresses, lipid products, hypoxia.

Question 4

name 3 congenital vascular anomalies?

Answer 4

• Berry aneurysms: a thin-walled arterial outpouchings in cerebral vessels, classically at branch points around the circle of willis, which can rupture leading to fatal intracerebral hemorrhage.
• Arteriovenous (AV) fistulas: abnormal connections between arteries and veins without an intervening capillary bed.
• Fibromuscular dysplasia: focal irregular thickening of the walls of medium and large-sized muscular arteries due to a combination of medial and intimal hyperplasia and fibrosis. This can lead to luminal stenosis.

Question 5

what factors determine blood pressure?

Answer 5

Cardiac output and total peripheral vascular resistance

Question 6

what are the functions of cardiac output?

Answer 6

stroke volume and heart rate.

Stroke volume is determined by filling pressure, which is regulated by blood volume (sodium homeostasis)

Question 7

what factors determine peripheral resistance?

Answer 7

regulated at the level of the arterioles by:

• neural and humoral inputs
• autoregulation (constrict at higher pressures)
• tuned via tissue pH and hypoxia and metabolic demand

Question 8

how much does the kidney filter per day average?

Answer 8

170L/day

Question 9

Renin is released by the kindey in response to what?

Answer 9

• low blood pressure
• elevated levels of circulating catecholamines
• low sodium levels

Question 10

what does Renin do upon release?

Answer 10

cleaves angiotensinogen to angiotensin I. which is turned into angiotensin II by angiotensin-converting enzyme (ACE).

Question 11

what does angiotensin II do?

Answer 11

raises blood pressure via:

• inducing vascular SMC contraction
• stimulating aldosterone secretion by the adrenal gland
• increasing tubular sodium resorption

Question 12

what pressure is considered to increase the risk of hypertension?

Answer 12

sustained diastolic pressures greater then 90mmHg or sustained systolic pressure in exceess of 140mmHg are reliably associated with an increased risk for atherosclerosis.

Question 13

Pathogenesis of hypertension?

Answer 13

my be primary (idiopathic/essential) = environmental and genetic.
secondary to an identifiable underlying condition (renal disease, adrenal disorders)
-Genes: aldostrone metabolism defect causing increased aldosternone secretion increased salt and water resorption and plasma volume expansion.
-Mutation affecting sodium resorption channels causing excess re-absorption as the channels are not degraded.

Question 14

what is the stereotypical response to vascular injury?

Answer 14

there is a thickening of the vessel wall.

loss of endothelial cells stimulates SMC growth, ECM synthesis and thickening of vessel wall.

Question 15

what are the 4 types of atherosclerosis?

Answer 15

• arteriolosclerosis: small arteries and arterioles are effected and may cause downstream ischemic injury. this also has 2 forms:
  1. hyaline: hyaline thickening of vessel.
  2. Hyperplastic: onion skin concentric thickening make of SMC.
• monckeberg medial sclerosis: calcific deposits in muscular arteries.
• Fibromuscular intimal hyperplasia: muscular arteries larger than arterioles.
• atherosclerosis: hardening, atheromas form which can rupture.

Question 16

structure and make-up of the atheromatous plaque.

Answer 16

FIBROUS CAP:
SMC, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularization
NECROTIC CENTER:
cell debris, cholesterol crystals, foam cells, calcium.

Question 17

what are the constitutional risks for atherosclerosis?

Answer 17

• Genetics
• Age
• Gender

Question 18

what are the modifiable major risk factors for atherosclerosis?

Answer 18

• hyperlipidemia (hypercholesterolemia)
• hypertension
• smoking
• diabetes (2 fold increase in myocardial infraction, and 100 fold increase in atherosclerosis induced gangrene of the lower extremities).

Question 19

Pathogenesis of atherosclerosis?

Answer 19

• Endothelial injury (increase permeability, leukocyte adhesion, and thrombosis
• Accumulation of pipoprotiens (oxidized LDL and cholesterol crystals in vessel walls.)
• Platelet adhesion
• Monocyte adhesion to the endothelium, migration into the intima, and differentiation into macrophages and foam cells.
• lipid accumulation within macrophages, which respond by releasing inflammatory cytokines
• SMC recruitment due to factors released from activated platelets, macrophages, and vascular wall cells.
• SMC proliferation and ECM production.

Question 20

what mechanisms does dyslipidemia contributes to atherogenesis?

Answer 20

• hyperlipidemia can impair endothelial function by increasing oxygen free radicals which accelerate NO decay damping its vasodilator activity)
• lipoproteins accumulate withing the intima, where they are hypothesized to generate 2 pathogenic derivatives, oxidized LDL and cholesterol crystals. LDL oxidized by ROS. which are taken up by macrophages to form foam cells. Oxidized LDL stimulates the local release of growth factors, cytokines, chemokines, increased monocyte recruitment.

Question 21

clinically important changes to atherosclerotic plaques are?

Answer 21

• Rupture, ulceration, or erosion of lumin surface exposing thrombogenic surface.
• hemorrhage into a plaque; rupture into the overlying firbous cap or of the thin-walled vessels in the areas of neovascularization (proliferation of small blood vessels). The hematoma could rupture the plaque.
• Atheroembolism: rupture plaque discharging debris.
• Aneurysm formation: Atherosclerosis-induced pressure or ischemic atrophy of the underlying media with loss of elastic tissue.

Question 22

what are the clinical consequences of atherosclerosis?

Answer 22

• myocardial infraction (heart attack)
• cerebral infraction (stroke)
• aortic aneurysm
• peripheral vascular disease (gangrene of extremities)

Question 23

what is critical stenosis?

Answer 23

a tipping point at which chronic occlusion limits flow so severely that tissue demand exceeds supply. 70% occlusion.

Question 24

stable angina definition?

Answer 24

brief periods of pain. Often related to the heart with chest pain upon physical exertion.

Question 25

what is intermittent claudication?

Answer 25

ischemic leg pain, induced by exercise.

Question 26

what are the 3 changes that a plaque could experience?

Answer 26

• Rupture/fissuring, exposing highly thrombogenic plaque constituents.
• Erosion/ulceration, exposing the thrombogenic subendothelial basement membrane to blood.
• Hemorrhage into the atheroma, expanding its volume.

Question 27

what happens to a plaque during inflammation?

Answer 27

plaque inflammation increases collagen degradation and reduced collagen synthesis, thereby destabilizing the mechanical integrity of the cap.
Statins can be used to reduce inflammation.

Question 28

the distinction between stable and unstable plaques.

Answer 28

• Stable: thick fibrous cap that can produce symptoms related to chronic ischemia by narrowing vessels.
• Unstable: can cause dramatic and potentially fatal ischemic complications related to acute plague rupture, thrombosis or embolization. These have thin caps and large lipid cores.

Question 29

shape classification of aneurysms?

Answer 29

Saccular aneurysms: outpouchings

Fusiform aneurysms: circumferential dilation up to 20cm in diameter

Question 30

the pathogenesis of aneurysms?

Answer 30

• Inadequate or abnormal connective tissue synthesis: mutations in TGF-b receptors that regulate SMC proliferation and matrix synthesis.
• Excessive connective tissue degradation: increased matrix metalloprotease expression by macrophages in atherosclerotic plaque can contribute to aneurysm development.
• Loss of SMC’s to change in their phenotype: thickening of the intima can cause ischemia of the inner media by increasing the diffusion distance from the lumen.

Question 31

Abdominal aortic aneurysm is caused by what 2 faced factors?

Answer 31

• ECM degradation mediated by proteolytic enzymes released from inflammatory infiltrates in atherosclerotic lesions.
• atherosclerotic plaques also compromise the diffusion of nutrient and wastes between the vascular lumen and the arterial wall causing the SMC to degrade.

a combination of these effects causes artery thinning.

Question 32

clinical consequences of Aortic artery aneurysm?

Answer 32

• Obstruction: vessel branching off the aorta resulting in ischemia of the kidneys, legs, spinal cord, or GI tract
• Embolism: of atheromatous material or mural thrombus
• Impingement of adjacent structures: compression of a ureter or erosion of vertebrae by the expanding aneurysm.
• An abdominal mass that stimulates a tumor
• Rupture: into the peritoneal cavity or retroperitoneal tissues, leading to massive, often fatal hemorrhage.

Question 33

define vasculitis?

Answer 33

a general term for vessel wall inflammation. The 2 most common pathogenic mechanisms of vasculitis are immune-mediated inflammation and direct vascular invasion by infectious pathogens.

Question 34

why is it important to be able to distinguish between infectious and immunologic mechanisms for vasculitis?

Answer 34

immunosuppressive therapy is appropriate for immune-mediated vasculitis but could exacerbate infectious vasculitis,
physical and chemical injury, including that due to radiation, mechanical trauma, and toxins, also can cause vasculitis.

Question 35

what are the main immunologic mechanisms underlying noninfectious vasculitis?

Answer 35

• immune complex deposition
• anti-neutrophil cytoplasmic antibodies
• anti-EC antibodies.