Week 5 - Plasma Osmolarity Flashcards
If water intake>water excretion then plasma osmolarity…
…decreases
How much urine is produced on average per day?
-1.5L
What senses changes in plasma osmolarity?
-Hypothalamic osmoreceptors in OVLT
What two pathways are activated through the hypothalamic osmoreceptors?
- ADH
- thirst
What is the result of ADH secretion?
-Decreased renal water excretion
What is the result of activating thirst pathway?
-Increased water intake
How are hypothalamic osmoreceptors exposed to plasma?
-Fenestrated leaky endothelium which senses changes in plasma osmolarity directly
Besides from increased plasma osmolarity, what else activates ADH and thirst pathways?
-Decreased ECF volume
Which efferent pathway of the hypothalamic osmoreceptors is most sensitive?
- ADH (occurs at 1% change)
- Thirst occurs at 10% change)
How is ADH secretion controlled?
-Negative feedback loop
What is the ultimate effect of ADH on the urine?
-Produces a low volume of concentrated urine
What effect does ADH have on the CD?
-Increases permeability to water and urea
What happens if plasma osmolarity decreases?
-No ADH stimulation -> CD is impermeable to water -> diuresis (high volume hypotonic urine)
Why is the increasing gradient in the interstitium of the kidney essential?
-Allows water to be drawn out when ADH is present producing concentrated urine
What is the mechanism of ADH?
-Causes aquaporin 2 channels to be inserted into the apical membrane of CD and late DCT so water can be resorbed
What happens to the permeability of CD and late DCT when ADH removed?
-AQP2 channels retrieved by endocytosis so permeability is removed
Which AQP channels are always present in basolateral membrane?
-AQP 3+4
What other effects does ADH have besides AQP channels?
- Causes vasoconstriction of glomerulus to decrease the effective filtering surface area
- Increases Na, K+ and Cl- resorption in ascending limb due to urea -> causes a more hypotonic filtrate at top of loop
- Increases K+ secretion in cortical CD
Describe the effect on the response to plasma osmolarity when there is a change in blood volume/pressure
- Decreased blood volume -> lower osmolarity is tolerated as you need to maintain blood volume and therefore tolerate the lower osmolarity in order to increase volume
- Increased blood volume -> Higher osmolarity tolerated as you want to reduce your blood volume so excrete more water
What is diabetes insipidus?
- A condition caused by the pituitary gland not producing enough ADH or insensitivity of the kidney to ADH
- More water is excreted than wanted resulting in polyuria and polydipsia, with a possible resulting hyponatraemia
What is syndrome of inappropriate antidiuretic hormone secretion (SIADH)?
- A syndrome characterised by excessive release of ADH from the posterior pituitary or another source (small cell carcinoma of lung)
- Results in dilutional hyponatraemia as the total body fluid is increased
What is the corticopapillary osmotic gradient?
-The increasing osmotic gradient from isotonic to hypertonic between the cortex and the renal papilla
What 3 factors are the main contributors to the corticopapillary gradient?
- Active transport of NaCl in thick ascending limb
- Urea recycling
- Vasa recta which maintains the gradient
What is an effective osmole?
- Any solute which increase the osmolarity of a solution
- To effect the osmolarity a solute must not be able to freely diffuse across the membrane or be transported
Why is urea an ineffective osmole in the body but an effective osmole in the kidney?
- In the body urea is transported across membranes ie an ineffective osmole
- In the kidney the tubule is impermeable to urea making it an effective osmole
Why is the thick ascending limb crucial in the generation of the corticomedullary gradient?
-Actively transports salts out of the filtrate into the interstitium without water following therefore increasing the osmolarity of the interstitium
Explain how urea contributes to the corticopapillary gradient and how its contribution differs in the presence of ADH
- Urea is normally reabsorbed from the medullary CD into the interstitium
- This causes an increase in the osmolarity of the interstitium
- In the absence of ADH, the filtrate in the CD is hypotonic and thus there is no driving force for urea
- When ADH is present, water has been resorbed and the concentration of urea in the medullary CD is high, generating a large driving force for urea resorption. Also ADH makes the medullary CD more permeable to urea. These factors together contribute to the corticopapillary gradient
Explain urea recycling
- As the concentration of the urea in the medullary interstitium increases, the driving force for passive urea secretion into the thin ascending limb of henle is increased.
- This serves to increase the urea concentration in the medullary CD which in turn increases the driving force for urea reabsorption to contribute to the medullary corticopapillary gradient
Explain how the ascending limb of loop of henle sets up the corticopapillary gradient (counter-current multiplier)
- Ascending limb impermeable to H2O but permeable to NaCl and Urea
- Urea secreted into the thin ascending loop from the interstitium
- Na is pumped out of the ascending loop, raising the osmotic pressure outside and lowering it inside (max gradient is 200mosm/L)
- Water diffuses out of descending limb into interstitium and thus the filtrate in descending limb has higher osmolarity
- Fresh filtrate enters and pushes the concentrated fluid into the ascending limb
- Na is pumped out of the concentrated filtrate into the interstitium, but osmolarity cannot reach as low as 1st round as started from a more concentrated filtrate
- Pumping of Na, osmotic flow and filtration flow all occur simultaneously
- The third round of Na pumping raises the interstitium more and so on
- The final gradient is limited by diffusional processes
How is the counter-current multiplier maintained?
-Vasa Recta flow in the opposite direction to fluid flow in the tubule maintaining the osmotic gradient by maximally reabsorbing any water which diffuses out of the tubule
What features of the vasa recta allow maximal reabsorption of water?
- Flows in opposite directions to maximise gradients
- Slow flowing which means the blood can absorb some of the NaCl pumped out of the loop and mimic its surroundings -> as the interstitium becomes concentrated so does the vasa recta -> flows past CD -> water reabsorption
- As it passes through the concentrated interstitium past the descending limb it reabsorbs the water
- ie it mops up dilutional water and as it enters the cortex the blood is isotonic and fast flowing again
