Volume Regulation

Question 1

Define effective circulating volume.

What is the clinical usefulness of measuring it?

Answer 1

• The volume of arterial blood that is effectively perfusing tissues.
• It is used as an indicator for total extracellular water content.

Question 2

What is the juxtaglomerular apparatus?

Answer 2

The complex of the distal tubule in association with the renal afferent arteriole of the same nephron.

Question 3

What cells are contained within the afferent arteriole at the juxtaglomerular apparatus?

Answer 3

Granular (juxtaglomerular) cells.

Question 4

What is the macula densa?

Answer 4

A thickening of the wall of the distal tubule.

Question 5

What is the function of the cells of the macula densa?

Answer 5

To detect Na+ concentration.

Question 6

Describe the stages of the renin-angiotensin system.

Answer 6

1 - The macula densa detects low Na+ concentration in the distal tubule.

2 - The granular (juxtaglomerular) cells at the afferent arteriole are stimulated to produce renin.

3 - Renin converts angiotensinogen (from the liver and adipocytes) into angiotensin 1.

4 - Angiotensin converting enzyme (ACE) in the lungs converts angiotensin 1 into angiotensin 2.

5 - Angiotensin 2 causes efferent vasoconstriction, increasing GFR (first negative feedback mechanism).

6 - Angiotensin 2 increases Na+ reabsorption in the proximal tubule, increasing body Na+ and volume (second negative feedback mechanism by increasing GFR).

7 - Angiotensin 2 stimulates aldosterone release from the adrenal cortex.

8 - Aldosterone increases Na+ reabsorption at the distal tubule and the collecting duct, increasing body Na+ and volume (third negative feedback mechanism by increasing GFR).

Question 7

List 2 triggers for aldosterone release.

Answer 7

1 - Angiotensin 2.

2 - Hyperkalaemia.

Question 8

Why is it important that aldosterone is not the only mechanism by which angiotensin 2 regulates body volume?

Answer 8

• If aldosterone was the only mechanism for angiotensin 2, then K+ could not be regulated independently of volume regulation, because changes in K+ would have to also lead to changes in body volume (since K+ and angiotensin 2 both use aldosterone to mediate their regulation).
• Since there are other mechanisms of angiotensin 2, volume regulation can be regulated independently of K+.

Question 9

List 4 drug classes that inhibit the renin-angiotensin system.

Answer 9

1 - ACE inhibitors.

2 - Angiotensin 2 type 1 receptor (AT1) antagonists.

3 - Aldosterone receptor antagonists.

4 - Renin inhibitors.

Question 10

List 6 locations in the body where angiotensin 2 type 1 (AT1) receptors might be found.

Answer 10

1 - Heart.

2 - Lungs.

3 - Vessels.

4 - Kidney.

5 - Adrenal cortex.

6 - Brain.

Question 11

List 2 ACE inhibitors.

Answer 11

1 - Captopril.

2 - Enalapril.

Question 12

List 2 angiotensin 2 type 1 (AT1) receptor antagonists.

Answer 12

1 - Candesartan.

2 - Irbesartan.

Question 13

Give an example of an aldosterone receptor antagonist.

Answer 13

Spironolactone.

Question 14

Give an example of a renin inhibitor.

Answer 14

Aliskiren.

Question 15

Through which pathway do angiotensin 2 type 1 receptors mediate their effects?

Answer 15

The Gq pathway.

Question 16

Give an example of a side effect of ACE inhibitors.

Answer 16

Coughing.

Question 17

List 2 other ways by which angiotensin 2 increases circulating volume (other than those stated in the RAS card).

Answer 17

1 - Causes ADH release.

2 - Causes thirst.

Question 18

List 3 cardiovascular effects of haemorrhage.

Answer 18

1 - Decreased vascular volume (and pressure).

2 - Decreased cardiac filling (and output).

3 - Decreased tissue and organ perfusion.

Question 19

List the ways by which the renin-angiotensin system is triggered.

Answer 19

1 - Sympathetic nerves stimulate granular cells directly to secrete renin.

2 - Sympathetic nerves cause afferent vasoconstriction to further decrease perfusion pressure, which is sensed by the granular cells directly.

3 - Afferent vasoconstriction lowers GFR, so decreases distal Na+ and decreases wall tension, which is sensed by the macula densa.

4 - A fall in blood pressure causes a fall in pressure in the vasa recta, which increases fluid uptake from the renal interstitial space. This means that Na+ concentration will be lower at the distal tubule, which is sensed by the macula densa.

Question 20

Which sympathetic receptors are present on:

• The smooth muscle of the vessels supplying the kidney?
• The granular cells?

Answer 20

• The smooth muscle of the vessels supplying the kidney have alpha 1 adrenoceptors.
• The granule cells have beta 1 adrenoceptors.

Question 21

Via which pathway do alpha 1 and beta 2 adrenoceptors mediate their effects?

Answer 21

• Alpha 1 receptors use the Gq pathway.

- Beta 2 receptors use the Gs pathway.

Question 22

List 3 ways by which ADH release is increased following sudden volume loss.

Answer 22

1 - Decreased cardiac filling.

2 - Activation of the baroreceptor reflex.

3 - The central actions of angiotensin 2.

Question 23

Why does the acute response to haemorrhage involve hyponatraemia?

Answer 23

Because ADH release is increased following haemorrhage, which retains water but does not retain Na+.

Question 24

List 3 negative stimuli and 3 positive stimuli for ADH release.

Answer 24

Positive stimuli:

1 - Increased osmolality.

2 - Decreased volume.

3 - Nicotine.

Negative stimuli:

4 - Decreased osmolality.

5 - Increased volume.

6 - Alcohol.

Question 25

What is the primary effect of ADH?

Answer 25

To drop osmolality (rather than increase volume, which is its secondary effect).

Question 26

List 3 functions of atrial natriuretic peptide (ANP).

Answer 26

Has natriuretic functions:

1 - Increases cGMP activity in the kidney, resulting in dilation of the afferent glomerular arteriole, increasing GFR.

2 - Decreases Na+ / Cl- cotransport activity in the distal tubule.

3 - Decreases ENaC and Na+ / K+ ATPase activity in the cortical collecting duct.

Question 27

What stimulates atrial natriuretic peptide release?

Where is it produced?

Answer 27

• Increased atrial filling.

- It is produced by cardiac myocytes of the atria.

Question 28

To which receptors does atrial natriuretic peptide (ANP) bind?

Answer 28

ANPa and ANPb receptors (in the kidney).

Question 29

Give an example of a peptide that is similar to atrial natriuretic peptide (ANP) in function but is produced in the kidney.

Answer 29

Urodilatin.

Question 30

What effect do prostaglandins have on renal function?

Answer 30

They have a natriuretic function.

Question 31

Where in the kidney is dopamine produced?

Answer 31

In sympathetic nerve terminals in the proximal tubule.

Question 32

What effect does dopamine have on renal function?

Answer 32

It has a natriuretic function.

Question 33

To which receptors does dopamine bind to mediate its effects on renal function?

Answer 33

D1 and D2 receptors.

Question 34

How does dopamine mediate its effect on renal function?

Answer 34

1 - By inhibiting the Na+ / H+ exchanger in the proximal tubule (luminal / apical membrane).

2 - By inhibiting the Na+ / K+ ATPase activity (basolateral membrane).