Hypertensive Vascular Dz, Blood Pressure Regulation

Question 1

Describe the negative side affects to high blood pressure.

Answer 1

End organ damage

Major risk factor in atherosclerosis

Question 2

What is the BP value associated with increased risk of atherosclerosis?

Answer 2

Sustained >89/>139

Question 3

What is secondary HTN associated with? Give examples.

Answer 3

Associated with underlying renal and adrenal dz

Ex: Primary aldosteronism, Cushing syndrome, Pheochromacytoma

Question 4

Describe how secondary HTN occurs. How can you diagnose it during a physical exam?

Answer 4

Increased production of renin from ischemic kidney causes renal artery stenosis

A bruit can be heard on auscultation of affected kidney

Question 5

Essential HTN is idiopathic (arises spontaneously, cause unknown). However, what are the risk factors that may lead to this dz?

Answer 5

Prevalence and vulnerability increases with age and African-american ethnicity

Question 6

What other health problems may arise from essential HTN?

Answer 6

Cardiac hypertrophy,
Heart failure (hypertensive heart dz)
Multi-infarct dementia
Renal failure
Aortic dissection

Question 7

What happens with untreated HTN patients?

Answer 7

1/2 dies of ischemic heart dz or congestive heart failure

1/3 die of stroke

Question 8

What is the BP value associated with malignant HTN?

Answer 8

> 200/>120

Question 9

Describe what occurs with malignant HTN.

Answer 9

Rapid increase in BP, death within 1-2 yrs

Severe HTN
Renal failure
Retinal hemorrhage and exudates +/- papilledema

Often superimposed on pre-existing benign HTN

Question 10

What is the most common type of HTN?

Answer 10

Essential HTN (~90-95%)

Secondary HTN (~5%)
Malignant HTN (~5%)

Question 11

What is BP a function of? What influence it?

Answer 11

BP = Cardiac output (CO) X Peripheral Resistance

Influenced by multiple genetic and environmental factors

Question 12

What is cardiac output?

Answer 12

Heart rate and stroke volume

Question 13

What influences stroke volume?

Answer 13

Influenced by blood volume

BV regulated by renal sodium excretion or resorption (also mineralocorticoids and ANP)

Question 14

Where is vascular resistance regulated? What influences it?

Answer 14

Regulated at level of arterioles

Influenced by neural and hormonal inputs

• Neural = a/B-adrenergic
• Humoral = Constrictors (angiotensin 2, thromboxane, etc.), Dilators (Prostagladins, Kinins, NO)
• Local factors = auto regulation, pH, hypoxia

Question 15

How does the body regulate LOW blood pressure?

Answer 15

In states of low volume or low peripheral resistance (or a decreased glomerular filtration rate), RENIN is released by juxtaglomerular cells in the afferent arterioles in kidneys.

Angiotensinogen –> Angiotensin 1 by Renin

Angiotensin 1 –> Angiotensin 2 by ACE (endothelium)

A2 causes:

• Vasoconstriction
• Aldosterone by adrenal gland causing kidneys to reabsorb sodium and water –> increase in BP

Question 16

How does the body regulate HIGH blood pressure?

Answer 16

Volume expansion induces myocardial release of ANP leading to:

• Na excretion and diuresis
• Vasodilation

Question 17

HTN is occasionally controlled by ___?
HTN is secondary to ___?
Sustained HTN requires participation of ___?

Answer 17

Controlled by single gene DO

Secondary to renal dz, adrenal dz, and endocrine DO

Sustained HTN requires participation of Kidneys

Question 18

What are the 2 forms of small blood vessel dz?

Answer 18

Hyaline arteriosclerosis

Hyperplastic arteriosclerosis

Question 19

Describe Hyaline arteriosclerosis. How is it involved in nephrosclerosis?

Answer 19

Increase in smooth matrix synthesis
Plasma protein leakage across damaged endothelium

In nephrosclerosis due to chronic HTN, arteriolar narrowing of hyaline arteriosclerosis –> diffuse impairment of renal blood supply and glomerular scarring

Question 20

What is the histologically significant of hyaline arteriosclerosis?

Answer 20

Homogenous pink (hyaline) thickening of vessel wall –> luminal narrowing

Question 21

Describe Hyperplastic arteriolosclerosis.

Answer 21

Occurs in severe HTN

In malignant HTN, laminations are accompanied by fibrinoid deposits

Question 22

What is the histologically significant of hyperplastic arteriolosclerosis?

Answer 22

Smooth muscle cells form concentric lamellations (“onion skinning”) –> luminal narrowing

In malignant HTN, laminations are accompanied by fibrinoid deposits and vessel wall necrosis (necrotizing arteriolitis), particularly in kidney

Question 23

What is Arteriosclerosis?

Answer 23

“Hardening of arteries” (Large/middle arteries)

Arterial wall thickening and loss of elasticity

Question 24

What is Arteriolosclerosis?

Answer 24

Affects middle/small sm arteries and arterioles, may cause downstream ischemic injury

Question 25

What is Monckeberg medial sclerosis?

Answer 25

``` Affects = >50 years old Calcification of muscular arteries Internal elastic membrane involved No narrowing of lumen No clinical significance ```

Question 26

What is Atherosclerosis?

Answer 26

"Gruel", "Hardening" - PROCESS | Most frequent and clinically important pattern

Question 27

Atherosclerosis underlies the pathogenesis of?

Answer 27

Primary coronary, cerebral, and peripheral vascular dz

Question 28

In simple terms, what is the general worldwide distribution of patients suffering from atherosclerosis?

Answer 28

Extremely common, especially in the DEVELOPED world - this may be due to bad diets and decreased exercise Roughly 1/2 of all deaths in western world MI = 1/4 of all deaths in US

Question 29

Describe the overall pathogenesis of atherosclerosis.

Answer 29

Over time, vessel wall (endothelium) gets damaged. This caused build of fat, which later gets oxidized. This causes macrophage to travel to site and change into "foamy" macrophages. This begins to form a plaque. At the same, smooth muscle cells from layer underneath will travel towards the lumen and form a fibrotic cap around the macrophages.

Question 30

What is an atheroma? Why is it dangerous?

Answer 30

It is an atherosclerotic plaque. Raised lesion with soft grumous core of lipid covered by a fibrotic cap Besides mechanically obstructing blood flow, atherosclerotic plaques can rupture leading to catastrophic obstructive vascular thrombosis Plaque can also increase diffusion distance from lumen to media leading to ischemic injury and weakening of vessel wall, changes that may result in aneurysm formation

Question 31

Describe how age is a risk factor for atherosclerosis.

Answer 31

40-60 year old incidence increases by 5x Death rates from ischemic heart dz increase each decade premenopausal women are somewhat protected - possibly due to atheroprotective effect of estrogen

Question 32

Describe hypercholesterolemia and metabolic syndrome in regards to atherosclerosis.

Answer 32

Both are major risk factors for atherosclerosis HC is a major risk factor even in absence of other factors - it is sufficient to initiate lesion development Metabolic syndrome: assoc w/ central obesity Insulin resistance, HTN, dyslipidemia ( in. LDL, dec. HDL), hypercoagulability, & proinflammatory state may contribute to endothelial dysfunction and/or thrombosis

Question 33

What are some nonmodifiable risk factors for Atherosclerosis?

Answer 33

Genetic abnormalities Family HX increasing age Male gender

Question 34

What are some modifiable risk factors for Atherosclerosis?

Answer 34

``` Hyperlipidemia Hypertension Cigarette smoking Diabetes (incidence of MI 2X higher in pts W/ DM than in those w/o) Inflammation ```

Question 35

What molecule may be used to predict cardiovascular risk?

Answer 35

C-reactive protein (CRP)

Question 36

Where is endothelial injury more likely to occur in terms of atherosclerosis?

Answer 36

Hemodynamic turbulence Does not occur randomly or everywhere uniformly Most lesions tend to occur @ openings of existing vessels, branch points, posterior abd aorta - due to flow disturbances normally seen in these locations

Question 37

Describe how circulating lipids play a role in atherosclerosis.

Answer 37

Lipids in atheromatous plaques are predominantly cholesterol & cholesterol esters Accumulate in the intima, are taken up by macrophages & partially oxidized This modified LDL further accumulates w/in macrophages & smooth muscle cells, forming foam cells & a lesion known as a "fatty streak" This stimulates an inflammatory response to accumulation of this toxic form of LDL

Question 38

Describe the inflammatory process that occurs once macrophages detect the site of injury.

Answer 38

Accumulation of cholesterol crystals w/in macrophages is recognized by the inflammasome, which leads to IL-1 secretion More macrophages & T-cells are recruited & activated Inflammatory cytokines further activate endothelial cells, & growth factors stimulate smooth muscle cells to migrate to the intima & proliferate

Question 39

Name the molecules associated w/ smooth muscle proliferation.

Answer 39

PGDF (released by locally adherent platelets) Macrophages Endothelial cells Fibroblast growth factor Transforming growth factor - alpha (TGF-a)

Question 40

Describe what happens during smooth muscle migration, proliferation, & matrix deposition.

Answer 40

Smooth muscle cells proliferate and synthesize ECM, including collagen Atheromatous plaque = intimal expansion from foam cells & ECM, recruited inflammatory & smooth muscle cells, increased ECM The fibrofatty plaque becomes covered w/ a fibrous cap (dense collagen fibers) Center of plaque is necrotic, containing lipid, debris, foam cells & thrombus, surrounded by a none of inflammatory & smooth muscle cells

Question 41

What are the common sites of atherosclerotic involvement? (decreasing order)

Answer 41

``` Abdominal aorta Coronary arteries Popliteal arteries Internal carotid arteries Circle of Willis ```

Question 42

What are the complications of atherosclerotic plaque?

Answer 42

Rupture & ulceration - may lead to thrombosis Hemorrhage - may follow plaque rupture Embolism - may follow plaque rupture Aneurysm formation

Question 43

What are the consequences of atherosclerosis?

Answer 43

Stenosis of the arterial lumen | Acute plaque change

Question 44

Describe what happens during stenosis of the arterial lumen.

Answer 44

Plaques tend to continuity grow because of repeated cycling through the injury-healing process The lumen of the affected vessel gradually shrinks, eventually leading to ischemia downstream (a point known as critical stenosis - approx. 70% occluded) This may lead to chronic ischemia of myocardium, bowel, brain, the extremities, etc.

Question 45

Describe what happens with acute plaque change.

Answer 45

An acute thrombus may form over the plaque, occluding the artery. This may occur secondary to: - rupture of the plaque - erosion or ulceration of the plaque surface Hemorrhage into the plaque may acutely expand its volume

Question 46

Some plaques are more prone to rupture than others. Why?

Answer 46

Fibrous cap is continually degraded and resynthesized (remodeled) Increased inflammation in the plaque can accelerate fibrous cap degradation and inhibit its resynthesis; thus decreased collagen in the cap and weakening it Physical stresses can cause plaque rupture: - change in BP - vasoconstriction

Question 47

What are atherosclerotic emboli composed of? What happens when an embolus breaks off?

Answer 47

May be composed of fat droplets, nitrogen bubbles, atherosclerotic debris (cholesterol emboli), tumor fragments, bone marrow, even or even foreign bodies. Emboli travel through the blood until they encounter vessels too small to permit further passage, causing partial or complete vascular occlusion