Osmoregulation

Question 1

All body fluids, expect the interstitial space of the renal medulla have an osmolality of ………

Answer 1

285m mosm/kg

Question 2

What contributes to body fluid balance?

Answer 2

intake - food, drink, metabolism

losses - respiration, insensible water loss through skin, faeces

Question 3

Describe the control of ADH release

• where is osmolality detected?
• where is ADH synthesised and released from?
• what is the half-life of ADH?

Answer 3

• osmolality is detected int he arterioventral third ventricle (AV3V) region, where the BBB is incomplete
• AV3V neurones project to the supraoptic and paraventricular parts of the hypothalamus
• thy repsond to an increase in osmolality by increasing the release of ADH from the posterior pituitary
• ADH is synthesised in the cell bodies in the form of a pre hormone, cleaved as it descends to the pituitary
• ADH co-rereleased with its carrier peptide neurophysin (function unknown)
• ADH is unstable in the circulation, and so only has a half-life of 10 min

Question 4

What are the main receptors that ADH acts on?
Where are they located?
What signalling pathway do they use?
What are the effects of ADH here?

Answer 4

• V2 receptors
• on the cortical collecting ducts, basolateral membrane
• adenylyl cyclase –> PKA –> exocytosis of vesicles containing AQP2. Also acts to increase transcription of AQP2
• this increase permeability of collecting ducts to water so the urine becomes more concentrated

Question 5

What are the secondary receptors for ADH?
Where are they located?
What is their signalling pathway?
What are the effects of ADH here?

Answer 5

• V1 receptors
• smooth muscle cells of veins
• signal via PLC(IP3/DAG)
• this causes venoconstriction (important as ADH is stimulated to be released when plasma osmolality is high, mean plasma volume may be low, venoconstriction therefore helps to maintain blood pressure)

Question 6

Describe the structural organisation of AQP1

Answer 6

multisubunit oligomer organised as a tetramer of four identical subunits with a large glycan attached to only one

Question 7

What is the hypothesis of oxytocin?

What 3 things do we know about oxytocin?

Answer 7

Hypothesis: oxytocin triggers thirst

1. oxytocin is a key trigger of the milk let-down reflex
2. oxytocin is also an agonist at V1 and V2 receptors
3. breast feeding commonly triggers thirst

Question 8

How is thirst triggered?

Answer 8

• inadequate water intake causes an increase in osmolality of the plasma
• as for the regulation of ADH release, osmolality is detected in the anteroventral third ventricle (AV3V) region
• AV3V neurones project to the median preoptic area of the hypothalamus, which increases thirst

Question 9

What are is the body’s response to ‘binge’ drinking water

Answer 9

decreased osmolality causes a suppression of ADH release and suppression of thirst. This suggests, correctly, that there is tonic ADH release

Question 10

What is the urine production rate and urine osmolality in the following situations:

• maximal ADH
• no ADH

Answer 10

Max ADH 
- production rate = 300-400ml/day
- osmolality = 1300mOsm
No ADH
- production rate = 25L/day
- osmolality = 60-90mOsm

Question 11

What is the effect of drinking sea water?

Use calculations to explain your answer.

Answer 11

Osmolality = 2000mOsm

To clear 1kg of sea water will require 2000/1400mOsm of water to clear

Question 12

Why is it really important to not make formula feeds for neonates too concentrated?

Answer 12

neonates can only produce osmolality of 500mOsm.

Question 13

Not all dietary osmolites are equal.

What are the dominant osmolytes?

Answer 13

Na+ and K+

Question 14

Do carbohydrates contribute to osmolality? Why?

Answer 14

Carbohydrates

• converted to simple sugars, are transported into cells, so don’t contribute significantly to osmolality
• except in diabetes mellitus
• glucose in cells is oxidised to CO2 and water so only transiently increases osmolality

Question 15

Do proteins contribute to osmolality? Why?

Answer 15

Proteins

• broken down into AA’s, transported into cells, plasma change is osmolality is small
• nitrogen is removed through urea, which has a high renal clearance; so while the flux is high, the contribution to osmolality is low

Question 16

What is the fate of oral ingestion of KCl? What are the consequences?

Answer 16

• all cells relatively permeable to K+
• allows a large reservoir of K+
• KCl ingestion doesn’t adversely affect osmolality; hyperkalaemia itself kills more quickly
• K+ is cleared from the kidney more rapidly than Na+ so while the flux is high, the contribution to osmolality is lower because the clearance is higher

Question 17

What is hyperosmolar hyperglycemic state (HHS)?

Answer 17

• in DM, the glucose conc can get so high that is becomes a large contributor to the osmolality
• glucose >33mM, osmolality approx. 320mOsm
• this hyperosmolality gives strong thirst drive, which if insufficient leads to cellular dehydration, and if sufficient to lower glucose levels leads to hyponatraemia
• this causes altered mental state, seizures and other neurological signs

Question 18

What are the two types of diabetes inspidus?

Answer 18

nephrogenic and central

Question 19

Key implication of osmotic regulation:

• if we change the water content of the body, ………… corrects the ……… change
• Suppose however that we ingest NaCl alone. This will ………. the body fluid osmolality, and will trigger …… release and an increase in ………… . This compensation will lead to an increased ………..
• If we change the solute content of the body, …………….. disturbs the body volume
• So, osmoregulation regulates concentrations, but not the …………..

Answer 19

osmoregulation, volume
increase, ADH, thirst, volume
osmoregulation
volume