Renal 3: Hormonal regulation of kidney

Question 1

What type of urine is made with ADH (vasopressin) and what does this mean for the osmolarity and volume of plasma

Answer 1

Increasing the reabsorption of water resulting in a concentrated urine.
As more water was put back into the blood, the plasma osmolarity decreases and the plasma volume increases

Question 2

Describe the path of ADH being made to being released into circulation

Answer 2

1. Osmoreceptors in the hypothalamus detect an increase in osmolarity / increase Na+ concentration in plasma
2. This triggers the precursor for ADH to be synthesised in the hypothalamus and stored in vesicles in the posterior pituitary.
3. When osmolarity increases (in dehydration) or there is an increase in Na+ in the ECF, ADH is released from the posterior pituitary to the blood

Question 3

How do osmoreceptors in the hypothalamus detect changes in osmolarity

Answer 3

They are shrink activated receptors on neurons. When the osmolarity of ECF increases, the cells shrink and this causes Cation ion channels to open. This allows Na+ to enter the cell which depolarises cell=> triggers APs.
When cells swell (osmolarity of ECF decreases) channels close, APs less frequent.

Question 4

How does ADH act on target tissue and where is this

Answer 4

ADH acts on receptors in the last section of nephron (convoluted distal tubule + collecting duct).

• It stimulates the insertion of vesicles containing aquaporin-2 into the apical membrane (facing tubule) of collecting duct epithelia.
• Water can then move freely from tubule into cell and then to the blood as the basolateral membrane is relatively permeable to water.

Question 5

What effect does alcohol have on ADH

Answer 5

It inhibits ADH, thus resulting in water not being reabsobed so dilute urine and thus possibility of dehydration.

Question 6

What solution is better for dehydration: isotonic or hypotonic + why

Answer 6

As water equilibrates throughout ICF and ECF, this decreases osmolarity so is good for dehydration
However isotonic solution is not good because there will be no net movement of water so osmolarity stays the same

Question 7

What is concentration of ADH proportional to in the blood and compare the threshold to thirst

Answer 7

[ADH] is proportional to plasma osmolarity. The threshold for it to start being produced is 280 mOsm. Thirst is less sensitive and has a threshold of 295 mOsm

Question 8

What affects the slope of the [ADH] vs Plasma osmolarity curve. Give eg for higher and lower …

Answer 8

Blood volume.
Higher blood volume decreases sensitivity: smaller slope, threshold higher

Lower blood volume increases sensitivity: bigger slope, lower threshold.

Question 9

What is a secondary input that triggers the release of ADH. How sensitive

Answer 9

Decrease in plasma volume or a decrease in Blood pressure by (10-15%) .
This causes reduced firing of Baroreceptors in atrium and large vessels and this stimulates the posterior pituitary to release ADH.
Less sensitive- requires relatively high changes.

Question 10

What is the purpose/effect of the Renin-Angiotension- Aldosterone system

Answer 10

It maintains balance of sodium.

It increases blood pressure by increasing blood volume by the water that follows sodium

Question 11

What are 3 triggers and production of Renin. Where

Answer 11

Trigger;

1a) . If there is decrease of sodium content in the distal tubule, this is sensed by Macula densa cells which increase prostaglandins.
1b) If there is a decrease in blood volume –> this will cause decrease in blood pressure in the afferent arteriole sensed by granular cells.
1c) High sympathetic activity (via baroreflex bc low BP)

Production: This triggers Juxtaglomerular granular cells in the afferent arteriole release Renin

Question 12

What is Renin and its effect

Answer 12

Renin is an enzyme which catalyses the rate limiting step of Angiotensin 2 production

Question 13

Describe the pathway of Angiotensinogen to Angiotensin 2 + where they come from

Answer 13

1. Angiotensinogen from liver converted to Angiotensin 1 by Renin.
2. Angiotensin 1 to Angiotensin 2 by Angiotensin converting enzyme in the lungs.

Question 14

How does Angiotensin 2 affect target tissues

Answer 14

1. It causes vasoconstriction of afferent arterioles to decrease glomerular filtration rate.-> increase Blood pressure.
2. It has small direct effect on reabsorption in the proximal convoluted tubule by stimulating Na+/H+ antiporters.
3. It stimulates the release of Aldosterone from the adrenal cortex.
   This increases sodium and water reabsoption (+ H+/K+ excretion) in the distal tubule (with presence of ADH)
   - This increases blood volume-> increases blood pressure

Question 15

What are the two things that trigger release of Aldosterone from the adrenal cortex

Answer 15

Increased Angiotensin 2 levels and increase K+ conc in the plasma

Question 16

What is the response to ingestion of salt

Answer 16

1. Increased salt conc in plasma increases the blood volume because water moves out of cells to plasma
2. Increased blood volume triggers:
   a) Increased atrial stretching=> release of ANP
   b) decreased release of renin=> less angiotension 2 which leads to increase GFR bc vasodilation and decreased aldosterone
3. Reduced reabsorption of NaCl by kidneys
4. Increased loss of NaCl in urine, and the water following it from plasma
5. Decreased blood volume

Question 17

How does Aldosterone increase reabsorption of sodium

Answer 17

Increases the transcription of Na/KATPase in the basal membrane therefore creating a greater gradient for activity of Na+ channels in apical membrane of principal cells in the collecting duct.

Question 18

What is the response to a haemorrhage

Answer 18

1.Haemorrhage decrease blood volume -> thus blood pressure

2. Sensed by Baroreceptors which trigger
   a) Posterior pituitary to release ADH
   b) Increase sympathetic nerve activity

-Sensed by Juxtaglomerular cels to secrete Renin-> increased Angiotensin 2 in blood.

3. From ADH: vasoconstriction, increased water absorption.
   From Symp : increased HR and vasoconstriction
   From Aldosterone: increased Na+ absorption
4. Increased blood volume & increased systemic vascular resistance==> Increased BP

Question 19

What is a haemorrhage

Answer 19

An isotonic loss of water and salt

Question 20

What is the timescale of the responses to restore blood volume

Answer 20

1. Autoregulation: Feedback (Regulation of filtration of 
glomerulus)
2. Nerves
3. Hormones
4. Thirst 
5. RBC replacement

Question 21

What is difference between ANP and ADH

Answer 21

ANP is triggered by stretching of atria (high blood volume)
and works to inhibit all Renin, ADH, Aldosterone release. Therefore increase GFR
-»Reduces Na+ reabsorption + water
Whereas, ADH works to increases water reabsorption

Question 22

What triggers thirst

Answer 22

Osmoreceptors in the hypothalamus that sense decreased plasma osmolarity.