S5) Control of Blood Pressure

Question 1

What is the formula for measuring blood pressure?

Answer 1

Pressure = flow x resistance

i.e maBP = CO x TPR

Question 2

What are the two different ways of regulating blood pressure?

Answer 2

• Short term regulation
• Long term regulation

Question 3

What does the baroreceptor reflex involve?

Answer 3

• Adjust sympathetic and parasympathetic inputs to the heart to alter CO
• Adjust sympathetic input to peripheral resistance vessels to alter TPR

Question 4

What are the advantages and disadvantages of the baroreceptor reflex in terms of the control of blood pressure?

Answer 4

• Advantages: controls acute changes in BP and produces rapid responses to changes
• Disadvantage: doesn’t control sustained increases because the threshold for baroreceptor firing resets

Question 5

What are the principles governing the medium and longer term control of blood pressure?

Answer 5

• Complex interaction of neurohumoral responses directed at controlling Na⁺ balance and thus extracellular fluid volume
• Control of extracellular fluid volume controls plasma volume (H₂O follows Na⁺)

Question 6

Identify the four parallel neurohumoral pathways control circulating volume and hence BP

Answer 6

• Renin-angiotensin-aldosterone system (RAAS)
• Sympathetic nervous system (SNS)
• Antidiuretic hormone (ADH)
• Atrial natriuretic peptide (ANP)

Question 7

Outline the Renin-angiotensin-aldosterone system

Answer 7

Question 8

Where is renin released from?

Answer 8

Renin is released from granular cells of juxtaglomerular apparatus (JGA) in the afferent arteriole of the glomerulus

Question 9

What stimulates renin released?

Answer 9

Renin release is stimulated by decreased circulating blood volume which reduces the perfusion pressure of the afferent arteriole

Question 10

Explain which three factors stimulate renin release

Answer 10

Question 11

What are the three effects of angiotensin II in RAAS?

Answer 11

• Vasoconstriction
• Stimulates release of aldosterone
• Na⁺ reabsorption at the kidney

Question 12

What are the two different types of Angiotensin II Receptors?

Answer 12

• AT1
• AT2

Question 13

The main action of angiotensin II is via AT1 receptor.

What type of receptor is this?

Answer 13

G-protein coupled receptor

Question 14

Describe the specific actions of angiotensin II at the following sites:

• Arterioles
• Kidney
• SNS
• Adrenal cortex
• Hypothalamus

Answer 14

Question 15

AngII stimulates aldosterone release from the adrenal cortex.

Describe the action of aldosterone on the kidney

Answer 15

⇒ Acts on principal cells of collecting ducts

⇒ Stimulates Na⁺ reabsorption (thus, H₂O)

⇒ Activates apical Na⁺ channel (ENaC) and apical K⁺ channel

⇒ Increases basolateral Na⁺ extrusion via Na/K/ATPase

Question 16

Relate the actions of Angiotensin converting enzyme and bradykinin

Answer 16

• Bradykinin has vasodilator actions
• ACE (aka kininase II) converts angiotensin I to angiotensin II & breaks down bradykin into further augment the vasoconstriction effect of AngII

Question 17

Explain the three ways in which the SNS controls blood pressure

Answer 17

• Increased sympathetic stimulation reduces renal blood flow (afferent vasoconstriction, increase GFR and Na⁺ excretion)
• Stimulates Na⁺ reabsorption in PCT (apical Na/H-exchanger and basolateral Na/K ATPase)
• Sympathetic stimulation of renin release from JGA

Question 18

When is ADH released?

Answer 18

• Increased plasma osmolarity
• Severe hypovolaemia

Question 19

What is the main role of ADH?

Answer 19

ADH aims to form concentrated urine by retaining water to control plasma osmolarity

Question 20

Explain the three ways in which ADH controls blood pressure

Answer 20

• Increases H₂O reabsorption in distal nephron (AQP2)
• Stimulates Na⁺ reabsorption (stimulates apical Na/K/Cl co-transporter in thick ascending limb)
• Vasoconstriction

Question 21

Atrial natriuretic peptides are synthesised and stored in atrial myocytes.

What stimulates and inhibits their release?

Answer 21

• Stimulated release: distension in atrial cells (greater blood volume)
• Inhibited release: reduced filling of heart (lesser blood volume

Question 22

ANP acts in opposite direction to the other neurohumoral regulators.

Describe the two ways in which it controls blood pressure

Answer 22

• Vasodilates the afferent arteriole (increased GFR)
• Inhibits Na⁺ reabsorption along the nephron (natriuresis)

Question 23

Explain how prostaglandins (mainly PGE2) act as a buffer to excessive vasoconstriction produced by SNS and RAAS

Answer 23

• Act as vasodilators
• Enhance glomerular filtration and reduce Na⁺ reabsorption

Question 24

How is Dopamine formed?

Answer 24

Dopamine is formed locally in the kidney from circulating L-DOPA

Question 25

Where are dopamine receptors found?

Answer 25

Dopamine receptors are present on renal blood vessels and cells of PCT & TAL

Question 26

What effect does dopamine have on blood pressure?

Answer 26

- Vasodilation of afferent arteriole - Reduces Na⁺ reabsorption (Inhibits Na⁺/H exchanger and Na/K ATPase)

Question 27

What is hypertension?

Answer 27

**Hypertension** is the sustained increase in blood pressure

Question 28

What are the different types of hypertension?

Answer 28

- **Primary hypertension** (95%) – cause is unknown - **Secondary hypertension** (5%) – due to underlying condition

Question 29

Classify hypertension into three different stages

Answer 29

Question 30

In Essential hypertension, there is no clear identifiable cause. Identify two possible influences

Answer 30

- Genetic factors - Environmental factors

Question 31

Provide four examples of common conditions which cause hypertension (secondary hypertension)

Answer 31

- Renovascular disease - Chronic renal disease - Hyperaldosteronism - Cushing’s syndrome

Question 32

In 4 steps, explain how renovascular disease leads to secondary hypertension

Answer 32

⇒ **Renal artery stenosis** reduces renal perfusion pressure in one kidney ⇒ Stimulated **renin release** ⇒ Activation of **RAAS** ⇒ **Vasoconstriction** and **Na⁺ retention** at other kidney

Question 33

Explain the two ways in which renal parenchyma disease can lead to secondary hypertension

Answer 33

- **Earlier stage:** loss of vasodilator substances - **Later stage:** Na⁺ and water retention due to inadequate glomerular filtration (volume-dependent hypertension)

Question 34

What are the three adrenal causes for secondary hypertension?

Answer 34

- Conn's syndrome - Cushing's syndrome - Tumour of the adrenal medulla

Question 35

Explain how Conn's syndrome leads to secondary hypertension

Answer 35

- Aldosterone-secreting adenoma - Hypertension and hypokalaemia ensues

Question 36

Explain how Cushing's syndrome leads to secondary hypertension

Answer 36

- Excess secretion of glucocorticoid cortisol - High [cortisol] acts on aldosterone receptors - Na⁺ and H₂O retention

Question 37

Explain how a tumour of the adrenal medulla can lead to secondary hypertension

Answer 37

**Phaeochromocytoma** – secretes catecholamines (noradrenaline and adrenaline) which increase sympathetic stimulation of kidneys and blood vessels

Question 38

Outline the wide array of hypertension complications in terms of: - Arterial damage - Increased afterload

Answer 38

Question 39

How does one treat secondary hypertension?

Answer 39

Treat the underlying pathological cause

Question 40

Outline the treatment of hypertension with non-pharmalogical approaches

Answer 40

- Exercise - Diet - Reduced Na⁺ intake - Reduced alcohol intake

Question 41

Outline the treatment of hypertension by targeting RAAS

Answer 41

- ACE inhibitors - AII receptor antagonists

Question 42

Outline the treatment of hypertension with vasodilators

Answer 42

- CCBs - α1 receptor antagonists (can cause postural hypotension)

Question 43

Outline the treatment of hypertension with diuretics

Answer 43

- Thiazide diuretics – reduce circulating volume - Aldosterone antagonists (spironolactone)

Question 44

Why aren't beta blockers often used for the treatment of hypertension alone?

Answer 44

Less commonly used to treat hypertension as blocking β1 receptors in the heart will reduce effects of sympathetic output (HR & contractility)

Question 45

What are the target organs of clinical cardiovascular disease?

Answer 45

- Brain - Eyes - Heart - Kidneys - Arteries