S2: Blood Pressure and the Kidney

Question 1

Explain the relationship between salt intake, age and blood pressure

Answer 1

High Na+ intake –> Higher blood pressure

Higher age –> Higher blood pressure

This is why people with the western ‘civilised’ diet have higher blood pressure compared to the ‘primitive’ people diet as they consume more sodium

Question 2

Where in ECFV is Na+ found

Why does intracellular volume have so little Na+?

Answer 2

Na+ is the major electrolyte in:

• Interstitial fluid
• Plasma fluid
• Cerebrospinal fluid

ICF has little Na+ due to the Na+/K+ ATPase pump (pumping 3 Na+ into external enviroment)

Question 3

Why is Na+ levels linked to blood pressure?

Answer 3

Changes in Na+ balance lead to changes in osmolarity
- ADH is released

Changes in ECFV
as H2O moves with Na+ in kidney.
- H2O moves through ADH stimulated aquaporin channels in collecting duct

Changes in ECFV affect blood volume

BP=CO x TPR
SV is a major determinant of CO (CO=HR x SV). Increase BV, increase EDP, increased stretch (starlings) leads to increase SV. This increases CO which then increases BP. Increase in SV also increases pressure exerted on vessel wall which also increases BP.

Question 4

What is the long term and short term control of blood pressure?

Answer 4

• Regulate Na levels – blood volume – long-term control of blood pressure

In contrast to baroreceptors – short-term control (min to min)

Question 5

How does the CVS controls Na+ levels?

Answer 5

1. Change in Na+ intake
2. Change ECFV
3. Afferent pathways detect change (cardiac volume receptors, baroreceptors, renal arterial pressure)
4. Efferent pathways:
   - Neuronal: Symp nervous system
   - Haemodynamic: Increase/Decrease GFR, Pressure Natriuresis
   - Hormonal: RAAS, ANP
5. Change in Na+ output

Question 6

Summary of the RAAS system

Answer 6

1. Stimulants: Symp nerve activity, Na+ intake, ECFV, BP
2. Kidney releases Renin
3. Liver releases Angiotensin I
4. ACE converts it to Angiotensin II
5. Ang II acts directly of VSMC - vasoconstriction - Increase BP
6. AT1R converts it to Aldosterone (adrenal gland)’
7. Aldosterone acts at the kidney increasing Na+ reabsorption so there is a decrease of Na+ in urine

Question 7

Explain renin secretion in the role of Na+ conservation

what stimulates it?

Answer 7

There are modified smooth muscle cells along the afferent arteriole called renin secreting juxtaglomerular cells

Factors that stimulate renin release:

1. Decrease BV and BP leads to decreased renal blood flow. This is sensed by afferent arteriole mechanoreceptors not being stretched as much
2. Decreased Na+ levels at macula densa
3. Sympathetic nerve activation of B2 adrenoreceptors (normally activated by an increase of BP and BF is needed.This is due to changes in baroreceptor activity and cardiac volume receptors.

Question 8

What is aldosterone?

Answer 8

It is a steroid hormone synthesised in the zona glomerulosa of the adrenal gland. it is released by action of angiotensin II.

Question 9

What is the role of aldosterone in the kidney?

Answer 9

• Act at nuclear receptors inside cells (change 2 genes: increasing expression of ENaC and Na+/K+ ATPase genes)
• This increases Na+ reabsorption at distal tubular sites into plasma
• Reabsorption of water in plasma as it follows Na+
• Results in increased renal excretion into tubular fluid - excess aldosterone can lead to hypokalaemia

Question 10

Explain Na+ excretion - caridac natriuretic peptides

What stimulates and releases it , the effects of ANP

Answer 10

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) found in specialised cardiac myocytes in RA (respond to increased stretch) so ANP and BNP is released by increased cardiac filling pressures (­ECFV)

EFFECTS OF ANP

Renal: Natriuresis (increase Na+ excretion), Diuresis (Increase H2O excretion)

Vasculature: Vasodilation by stimulation of PKGin VSMC (decrease sytemic BP)

Hormonal: Decrease renin secretion, derease aldosterone secretion

Question 11

What system opposes RAAS?

Answer 11

ANP

Question 12

Explain Na+ excretion and pressure natriuresis

Is there GFR changes?

Answer 12

Increase renal Na+ excretion due to a rise in renal arterial pressure (increased blood volume)
- GFR changes not involved as renal arterial pressure does not increase GFR due to powerful renal arterial auto-regulation (constriction of afferent arteriole)

Question 13

What is Natriuresis?

Answer 13

Excretion of sodium in the urine

Question 14

What happens to blood volume when there us a rise in medullary capillary pressure?

Answer 14

• Rise in medullary capillary pressure (when there is high capillary pressure at efferent arteriole due to not much autoregulation)
• Increases fluid filtration (into interstitial space) and interstitial pressure
• Prevent tubular reabsorption
  Reduction in blood volume

Question 15

Classification of Hypertension

Answer 15

Present when:

• Systolic > 140 mmHg
• Diastolic >90 mmHg

Classified as:

• Secondary (identifiable cause - <10% cases)
• Essential (unknown cause - >90% cases)

Essential hypertension may involve abnormal handling of Na+ balance

Question 16

What are some secondary causes of hypertension?

Answer 16

Some involve excess renal reabsorption and abnormalities in hormone secretion

• Liddle’s syndrome
• Conn’s syndrome
• Renal artery stenosis

Question 17

Describe Liddle’s Syndrome

Answer 17

It is a rare genetic form of high blood pressure associated in epithelial Na+ sodium channal (ENaC)

• Increases ENaC activity
• Increases renal Na+ retention
• Supresses renin/aldosterone

This causes increased ECVF which leads to increased blood pressure even with low renin/aldosterone (feedback system switches off RAAS).

Increased BP therefore due to ENaC

Question 18

Describe Conn’s Syndrome

Answer 18

It is the overprodcution of aldosterone due to an adrenal gland tumour (adenoma)

Consequences of raise aldosterone for electrolytes and ECFV:

• Renal sodium reabsorption
• Increased ENaC, Na+/K+ ATPase
• Increased K+ excretion
• ECFV expansion leads to decreased renin

Conn’s syndrome - primary aldosteronism
High blood pressure - low renin levels - high aldosterone

Question 19

Describe Addison’s disease

Answer 19

Addison’s disease, insufficient release of aldosterone, chronic Na loss, large ¯ ECFV, severe hypotension, leading to collapse and death

Question 20

How does renal artery stenosis affect blood pressure?

Answer 20

Renal artery stenosis = abnormal narrowing of vessel

Decrease in renal artery pressure due to pressure drop downstream caused by stenosis
This leads to decreased blood flow.

This activates the RAAS system
- Aldosterone causes Na+ retention and Ang II vasoconstricts VSMC. Both of these cause high blood pressure.

Question 21

Describe essential hypertension

Answer 21

Causes unknown

It is though that genetic predisposition and enviromental factors (e.g. lifestyle and diet) cause intermediate phenotypes that can lead to increased blood pressure

It could also be caused by defects in renal Na+ handling

Question 22

What are frontline anti-hypertensive treatments?

Answer 22

Agents that decrease RAAS

e.g. ACE inhibitors, Ang II