Physiology of the Renal System V: Volume Regulation

Question 1

What kind of volume is regulated since extracellular volume cannot easily be measured?

Answer 1

Effective circulating volume

since they change together

Question 2

What is the juxtaglomerular apparatus (JGA)?

Answer 2

complex of the late distal tubule in association with renal afferent arteriole.
There are granular cells in the afferent in the arteriole.

Question 3

What is the macula densa?

Answer 3

Thickening of the all of the early distal tubule which is specialised to signal to the granule cells to regulate renin production.

Question 4

What is the aim of the renin-angiotensin-aldosterone system?

Answer 4

increase the effective circulating volume.

Question 5

Explain the renin-angiotensin system?

Answer 5

Low Na in distal tubule
Macula densa cells detect this
JGA granule cells release renin.
Renin converts angiotensinogen to angiotensin 1
This is then cleaved to angiotensin 2 

Angiotensin 2 has its effects on the body

Question 6

What are the effects of angiotensin 2?

Answer 6

Cause vasoconstriction of efferent arteriole (leads to increase GFR)

Increase Na reabsorption in the PCT

Aldosterone release from adrenal cortex.

Question 7

What does aldosterone do?

Answer 7

Increases Na reabsorption in the DCT and CD increasing both Na and water which reverses the fall in distal Na delivery and hence leads to an increased GFR.

Question 8

What are the main triggers for aldosterone release?

Answer 8

ATII, Hyperkalaemia

Question 9

What dose spironolactone do?

Answer 9

Acts in the collecting tubules and ducts

blocks the effect of aldosterone.

Moderately effective diuretics

Used in heart failure

Question 10

How can the renin-angiotensin system be inhibited?

Answer 10

Inhibited in 4 different locations.
ACE inhibitors (captopril)
AT1 receptor antagonists(candesartan)
Aldosterone receptor antagonists (Spironolactone)
Renin inhibiton (aliskiren)

Question 11

Why would you want to inhibit the renin-angiotensin system?

Answer 11

Control of blood pressure

Question 12

What is the main receptor of angiotensin II?

Answer 12

AT1 receptor
It is mainly coupled through Gq so it is linked to an increase in IP3/DAG signalling and increased Ca release from intracellular stores.

Question 13

How does angiotensin II increase circulating volume?

Answer 13

1. Vasoconstriction
2. Increase Na/H exchange in the PCT and hence proximal Na and water reabsorption.
3. Increase in aldosterone release from the adrenal cortex which increases distal Na absorption.
4. Cause ADH release
5. Causes thirst

Question 14

What is the effect of activating sympathetic innervation of afferent arteriole on GFR?

Answer 14

Vasoconstriction upstream of the granule cells causes a further fall in pressure sensed by these cells, and hence amplifies the fall in wall pressure generated by a fall in blood pressure.
Direct stimulating of renin release from granule cells.
Afferent arteriole vasoconstriction drops glomerular hydrostatic pressure to the glomerulus and hence lowers GFR

Question 15

What is the main sympathetic transmitter?

Answer 15

Noradrenaline.

Question 16

How does a fall in blood volume lead to renin release?

Answer 16

Fall in blood volume leads to venous tone fall
The fall in tone causes a fall in the pressure in the vasa recta and hence an increase in the uptake of fluid from the renal interstitial space.
Therefore the is a greater loss of fluid from the filtrate (descending limb of loop of Henle)
This decrease Na delivery to the DCT which acts as a stimulus to renin release.

Question 17

What is ANP?

Answer 17

Atrial Natriuretic peptide.

Question 18

What does ANP do?

Answer 18

Travels to the kidney where it decreases the activity of the Na/K/ATPase leading to an increase in the renal secretion of Na.

Question 19

What triggers ANP release?

Answer 19

Increased venous return leads to increased atrial filling and therefore increases ANP release.

Question 20

What are prostaglandins?

Answer 20

Family of signalling molecules

Question 21

What do PGE2 and PGI2 do?

Answer 21

Produced tonically.

Both increase Na excretion.

Question 22

What does dopamine do to Na?

Answer 22

Increases Na excretion (natriuretic)

Question 23

Where is dopamine synthesised?

Answer 23

Made in the kidneys (and other areas) from the sympathetic nerve terminals.

Question 24

What is the primary effect of ADH?

Answer 24

Drop osmolality by increasing water absorption.

Question 25

What factors increase ADH release?

Answer 25

Increased osmolality
Stress
decreased volume
nicotine.

Question 26

What factors reduce ADH release?

Answer 26

decreased osmolality
increased volume
alcohol

Question 27

What is the effect on osmoregulation from volume regulation?

Answer 27

Volume regulation disrupts osmoregulation and vice versa