Pathophysiology of Hypertension

Question 1

Define pulmonary hypertension and what is it cause by?

Answer 1

Increased pressure in the arteries of the lungs. The cause is often not know but can be due to hypoxia, endothelial disfunction, damage to blood vessels ect.

Question 2

Define systemic arterial hypertension

Answer 2

Condition of persistent non-physiologic elevation of system blood pressure

Question 3

What are the risk factors for hypertension?

Answer 3

• Multiple genetic and enviromental risk factors,
• Age
• Weight,
• Sex
• Race (decedents of afro-carribians more likely)
• Education status,
• Diet

Question 4

Describe the different classes of systemic hypertension

Answer 4

Stage 1 - Clinical BP of 140/90 or higher and a HBPM daytime average of 135/85 or more
Stage 2 - Clinic BP of 160/100 and HBPM daytime average of 150/95
Sever hypertension (crisis) - Clinic systolic BP of 180 or more and a diastolic BP of 110 or more.

Question 5

What is primary hypertension?

Answer 5

Known as idiopathic hypertension. This is where there is no apparent underlying cause but think lifestyle/genetics

Question 6

Describe the short term control of blood pressure?

Answer 6

Cardiac output (SVxHR) and total peripheral resistance , (BP= CO x TPR) which has neurohormonal and local control systems

Question 7

Long term control of BP?

Answer 7

Effective circulating volume by kidneys

Question 8

Briefly describe how the SNS controls BP

Answer 8

• Increase signalling to vascular smooth muscle cells of BV (a1 receptors) causing vasoconstriction and increase TPR.
• Increased signalling to pacemaker and contractile cells in heart (B1), this increases HR and contraction which increases CO.
• Adrenal gland secretion of adrenaline.
• Renin secretion (B1) which increases angiotensin 2, causes vasoconstriction which causes increase in TPR

Question 9

Briefly describe neurotransmission of the SNS

Answer 9

Preganglionic fibre releases Ach which binds to postganglionic fibre which releases noradrenaline which will then bind to target organ. In the case of adrenal medulla, the preganglionic fibre terminates directly on it.

Question 10

Where are the alpha adrenoreceptors located and what is their functional response?

Answer 10

Alpha 1 - Located in CV, GI tract and GU. It causes vasoconstriction and contraction of smooth muscle (GI sphincters + GU)
Alpha 2 - Neuronal, decreases transmitter release

Question 11

Where are the beta receptors and what are their function?

Answer 11

Beta 1 - Heart and kidneys. Increase HR, increase cadiac force and increases renin release.
Beta 2 - Lungs, SM, SkM. It causes bronchodilation, relaxation of visceral smooth muscle and vasodilation in SkM.

Question 12

Describe the affinities of adrenaline and noradrenaline for the adrenoceptors

Answer 12

• Noradrenaline has higher affinity for alpha receptors.

- Adrenaline has higher affinity for beta receptors

Question 13

What is angiotensinogen?

Answer 13

Precursor for angiotensin 1, it is synthesized by the liver and released into the circulation.

Question 14

What is renin and its functions

Answer 14

Proteolytic enzyme released by juxtaglomerular granular cells. It cleaves angiotensinogen into angiotensin 1

Question 15

Function of angiotenin 1?

Answer 15

No biological activity but is the precursor for angiotensin 2

Question 16

What converts angiotensin 1? and where is it found

Answer 16

Angiotensin converting enzyme (ACE) Which converts it into angiotensin 2. It is found in the vascular endothelium in the lungs and renal afferent/efferent arterioles.

Question 17

What is the function of angiotensin 2?

Answer 17

• Cause vasoconstriction which increases TPR
• Release of vasopressin (ADG) to increase reabsorbtion of H2O in kidneys which increases ECV.
• Stimulates secretion of aldosterone from zona glomerulosa of adrenal glands. Increases Na+ reabsorption in kidney which increases ECV

Question 18

Describe features of low renin hypertension

Answer 18

Subset of patients with primary hypertension. Becomes secondary if cause is know. More prevalent in older patients and patients of afro-Caribbean descent. Diagnosed using plasma aldosterone:renin ratio.

Question 19

What is endothelin 1 and what does it cause?

Answer 19

• Most potent endogenous vasoconstrictor
• Binds to ETa receptors on smooth muscle to cause vasoconstriction
• Binds to ETa receptors in cardiomyocytes to increase contractility.
• HOWEVER it also binds to ETb receptors which causes production of NO cauing vasodilation and promotes Na and H2O exceretion in kidneys.

Question 20

Is ET-1 seen in primary hypertension

Answer 20

Not commonly increased Primary but local levels may be increased.

Question 21

Describe features of nitric oxide (NO)

Answer 21

• Circulating factor, Lipophilic gas released from endothelial cells. It is potent vasodilator which has very short half life. It is chronic regulator of renal BF and increases Na+ excretion.

Question 22

Describe features of reactive oxygen species (ROS)

Answer 22

Patients with essential/idiopathic hypertension may have increased circulating hydrogen peroxide. The ROS in vasculature may uncouple enzymes which produce NO. Antioxidant treatment has no effect on high BP.

Question 23

What is secondary hypertension?

Answer 23

It is when there is an identifiable cause. Often occurs in younger patients and is more rare

Question 24

What are some of the causes of secondary hypertension?

Answer 24

• Renal parenchymal disease (eg, diabetic nephropathy and polycystic kidney disease)
• Renal vascular (eg, renal artery stenosis)
• Endocrine - Adrenal gland
• Prenancy (Eclampsia and pre-eclampsia)
• Coarctation of the aorta
• Drugs (eg, contraceptive pill and cocain)
• Obstructive sleep apnoea

Question 25

What are some of the consequences of systemic hypertension?

Answer 25

Heart - (Heart failure, left ventricular hypertrophy and myocardial infarctions)
Vasculature - Accelerated atherosclerosis, stroke and retinopathy)
Kidneys - Continued hypertension, albuminuria and end stage renal disease.

Question 26

What are some treatment strategies for hypertension?

Answer 26

Lifestyle modifications - Weight loss, reduced salt intake, increased fruit and veg intake, increased aerobic exercise, smoking cessation and stress reduction.
Use of medications