Hypertension

Question 1

What is the definition of hypertension?

Answer 1

An elevation of systolic and or diastolic pressure to the point where it increases the risk of cardiovascular disease (~140/90 mm Hg).

Question 2

What is isolated systolic hypertension?

Answer 2

The elevation in only systolic pressure.

Question 3

How does hypertension harm the cardiovascular system?

Answer 3

1. high pressure damages the endothelium of conduit arteries promoting development of atherosclerosis.
2. hypertension increases afterload which causes cardiac hypertrophy and ischaemia.
3. in isolated systolic hypertension, the fall in diastolic pressure may compromise coronary blood flow to wall of the left ventricle since this occurs only during diastole.
4. brain and kidney have high flow, low resistance vascular systems so their microcirculation are exposed to higher pressures and more pressure pulsalility which can damage them and lead to renal failure and stroke.

Question 4

What is midlife hypertension?

Answer 4

Mean, systolic and diastolic BP rise, associated with rise in TPR due to defect in sodium excretion by the kidneys and neurohormonal abnormalities.

Question 5

What is old-age hypertension?

Answer 5

Age-related arterial stiffening that leads to isolated systolic hypertension; systolic pressure rises but diastolic pressure typically falls so there is a small increase in mean BP.

Question 6

What is primary hypertension?

Answer 6

Has no identifiable cause in the patient, usually due to polygenic predisposition and environmental and lifestyle influences.

Question 7

What is secondary hypertension?

Answer 7

Cause can be identified in patient, could be due to renal issues, endocrine or identified monogenic syndromes.

Question 8

What systems affect BP via vascular tone and cardiac output?

Answer 8

ANS and baroreceptor reflex.

Question 9

What system affects BP via renal function and vascular tone?

Answer 9

Renin/angiotensin/aldosterone system.

Question 10

What are the determinants of mean arterial BP? (heart)

Answer 10

Cardiac output and TPR; heart rate and stroke volume affect CO. CVP-preload (degree of cardiac stretch) and Starling mechanism affects stroke volume. Blood volume is affected by excretion of sodium and water by the kidneys.

Question 11

How does the SNS affect mean arterial BP?

Answer 11

SNS increases arterial and venous tone, increases cardiac contractility and heart rate.

Question 12

How does the PNS affect mean arterial BP?

Answer 12

PNS decreases heart rate.

Question 13

How does RAAS affect mean arterial BP?

Answer 13

RAAS increases arterial and venous tone (constriction); it reduces sodium excretion so restores blood volume.

Question 14

How does pressure natriuresis affect mean arterial BP?

Answer 14

It increases sodium excretion which lowers blood volume.

Question 15

What does Guyton’s model state about the cause of hypertension?

Answer 15

It states that hypertension is due to an impairment of pressure natriuresis, resulting in decreased sodium and water excretion, thus a rise in BP. Blood volume increases but returns to normal, however, TPR increases due to autoregulation so BP remains high.

Question 16

What observations support Guyton’s hypothesis?

Answer 16

1. hypertension can be cured by a kidney transplant from a normotensive individual
2. monogenic hypertension almost invariably is due to a gene mutation important in renal function
3. studies show that arcuate and afferent arterioles which bring blood into the renal glomeruli are almost always narrowed in hypertensives which would result in reduced pressure natriuresis and increased blood volume

Question 17

What observations support models that propose that abnormalities in neurohormonal regulation of vascular tone exert long term effects on BP?

Answer 17

1. ~50% of those with hypertension have an overactive SNS which could cause an increase in vascular tone
2. in animal models of hypertension, hypertension can be cured by cutting the sympathetic nerves that innervate the blood vessels in the abdomen

Question 18

How do ACE-inhibitors lower BP?

Answer 18

ACE-inhibitors block the production of angiotensin II by blocking ACE, an enzyme required to convert angiotensin I to II, therefore, blood volume and pressure does not increase.

Question 19

How do ACE-inhibitors cause angioedemia and cough?

Answer 19

ACE is responsible for breaking down bradykinin to an inactive peptide thus when blocked by ACE-inhibitors, cause a cough and angioedema.

Question 20

How do angiotensin receptor blockers (ARBs) affect RAAS?

Answer 20

They block angiotensin II receptors and its effects.

Question 21

How do renin antagonists (Aliskiren) affect RAAS?

Answer 21

Blocks the binding of angiotensinogen to renin therefore prevents the synthesis of angiotensin I.

Question 22

How do calcium channel antagonists (CCBs) affect smooth muscle contraction?

Answer 22

Vascular selective CCBs inhibit constriction of arterioles by agonists by blocking voltage-gated calcium channels, thus decrease TPR. Non-selective CCBs also cause negative inotropy and chronotropy which reduced cardiac output.

Question 23

How do thiazide-like diuretics (chlortalidone, metalazone) affect BP?

Answer 23

They increase salt and water excretion by the kidneys which reduces blood volume and cardiac output. TPR also falls via an unknown mechanism.

Question 24

How do mineralocorticoid receptor (aldosterone) antagonists (MRA) affect sodium reabsorption?

Answer 24

Spironolactone blocks the effect of aldosterone therefore has a natriuretic/diuretic effect as sodium reabsorption is reduced in the collecting tubule.

Question 25

How do B-adrenergic receptor blockers affect BP?

Answer 25

They block sympathetic stimulation of the heart which reduces cardiac output; reduce renin secretion so cause vasodilation by lowering angiotensin II levels in plasma.

Question 26

How do a1-adrenergic blockers affect BP?

Answer 26

NA binds to a1-receptors on vascular smooth muscle cells, causing vasoconstriction, therefore a1-adrenergic blockers cause vasodilation and a fall in TPR.

Question 27

How does Methyldopa act as a antihypertensive?

Answer 27

Metabolised to a methyl noradrenaline in the brain. This is released from nerves and stimulates imidazoline receptors and a2 receptors, which both reduce the firing of sympathetic nerves. It may also inhibit the production of noradrenaline in peripheral sympathetic neurons.

Question 28

How does Imidazoline (I1) receptor agonists act as a anti-hypertensive?

Answer 28

Reduces sympathetic outflow by stimulation imidazoline receptors in the medulla.