Hypertension (Concepts)

Question 1

What are the types of hypertension?

Answer 1

1. Primary (essential) hypertension: Hypertension without any clear cause.
2. Secondar hypertension: Hypertension that’s secondary to another clinical condition.

Question 2

What is an example of secondary hypertension?

Answer 2

Hypertension caused by phaeochromocytoma (tumour of chromaffin cells in adrenal medulla secreting adrenaline)

Question 3

What are the blood pressures observed in hypertension (typically)?

Answer 3

Systolic: >140mmHg

Diastolic: >90mmHg

Question 4

What are the main contributing factors to essential hypertension?

Answer 4

1. Cardiac output (CO)
2. Total peripheral resistance (TPR)
3. The RAAS
4. The autonomic nervous system (ANS)
5. The endothelium
6. Vasoactive peptides

Question 5

How does CO and TPR contribute towards hypertension?

Answer 5

TPR is raised in hypertension while CO is fairly normal in many hypertensive patients.

Question 6

What is the possible mechanism for contributions of CO and TPR towards hypertension?

Answer 6

1. ↑ CO as a result of ↑ sympathetic activity.

↑ MAP as a result.

2. Reflex vasoconstriction of arterioles to protect capillary beds from the ↑ MAP, possibly mediated by ATII.
3. Tonic vasoconstriction of arterioles causes thickening of arteriolar walls, resulting in permanent increase in TPR.
4. CO eventually returns to normal due to down-regulation of the SNS?

Question 7

How does the ANS contribute towards essential hypertension?

Answer 7

• ANS has no clear causative role in hypertension.
• Drugs that modulate the ANS are used to treat hypertension.

Question 8

How does the endothelium contribute towards essential hypertension?

Answer 8

When the endothelium becomes damaged (e.g. by atheroma), the following changes may occur:

1. Endothelin secretion increases, which has pro-hypertensive effect
2. NO secretion decreases, which is a vasodilator

Question 9

What are the pro-hypertensive effects of endothelin?

Answer 9

1. Vasoconstriction
2. Activation of local renin-angiotensin systems (causing local vasoconstriction)

Question 10

How does the RAAS contribute towards essential hypertension?

Answer 10

• Some hypertensive patients have normal levels of renin.
• Inhibitors of the RAAS is not as effective in patients with normal levels of renin.

Question 11

What is Liddle’s syndrome?

Answer 11

• Mutations in ENaC causes increased expression and activity.
• This results in increased reabsorption of Na⁺ in DCT, causing water retention and hypertension.

Question 12

What is the mechanism of action of ACE inhibitors in treating hypertension?

Answer 12

1. Reduced activity of RAAS increases Na⁺ and water excretion, reducing TBV, MSFP and CO.
2. Increases circulating levels of bradykinin that promotes production of vasodilatory NO.

Question 13

What are the possible mechanisms of action of β-blockers in treating hypertension?

Answer 13

1. Decreased CO
2. Decreased SNS-mediated secretion of renin
3. Inhibition of presynaptic β₂ receptors that promote NA release

Question 14

What are the mechanisms of action of Ca_v antagonists in treating hypertension?

Answer 14

1. Relaxation of VSM and vasodilation, reducing TPR.
2. Mild diuresis.
3. Inhibition of aldosterone release?
4. Antagonist of baroreceptor response (not important in longer term).