Urine concentration and dilution Flashcards
Where is the countercurrent multiplication system set up
In the loop of Henle and the collecting duct
How is urine concentration increased
Na and Cl secretion in the thin and thick ascending limb (impermeable to water) causes a rise in osmolality in the interstitial fluid - This then creates an osmotic gradient in the thin descending limb causing water to move out of the lumen into the interstitial fluid (Impermeable to Na and Cl) - this causes a rise in osmolality as you go down the thin descending limb - Osmolality is highest at end of the thin descending limb
Osmolality then decreases going up the ascending limbs due to Na and Cl secretion - level with interstitial fluid at beginning of collecting duct
As fluid moves down - in the presence of arginine vasopressin - water moves out of the collecting duct - Increasing the osmolality in the lumen - increasing concentration of urine
Why is the loss of water in the thin descending limb so important
Multiplier effect - creates a larger osmotic gradient at the collecting duct for the loss of water - without it the osmotic gradient would be limited - reducing the ability to concentrate urine effectively
What KO for a channel in the thin descending limb causes problems with urine concentration
KO of the aquaporin 1 gene - less water secretion - osmotic gradient across the nephron is reduced - reduced ability for water secretion at the collecting duct so have problems in urine concentration - urine diuresis
Mutations in what genes lead to Bartter’s syndrome and why
NKCC2, Kir1.1 (ROMK) and ClCK (barttin) mutations on the epithelial cells of the thick ascending limb
Mutations on the apical side -
ROMK mutation prevents the action of NKCC2 (needs the recycling of potassium to function)
NKCC2 mutation - no longer able to reabsorb Sodium or chloride into the interstitial fluid - Osmolality remains constant so no osmotic gradient is formed - water remains in the tubule - polyuria, salt wasting, hypokalemia
Basolateral side - ClCK - can’t secrete chloride - same effect
What are the mutations that lead to diabetes insipidus and why?
Mutations in V2 receptors on principal cells of the collecting duct - also mutation in the gene required for aquaporin 2 production - even if the osmotic gradient is in place - water can’t be reabsorbed - polyuria
What percentage of the interstitial osmolality is produced by urea
50% - NaCl also 50%
Where does urea secretion occur
Early stages of collecting duct are impermeable to urea - urea concentration goes up along the collecting duct - Until vasopressin stimulates urea transporters - conc of urea is very high so has a large driving force to go into the interstitial fluid - providing 50% of the osmolality gradient.
How does countercurrent exchange occur in the vasa recta
Specialized blood system that goes down into the medulla then back up -
Osmolality is low as it enters the medulla - as it goes down - interstitial fluid osmolality goes up - this creates an osmotic gradient - water moves out the plasma into the interstitial fluid and takes up solutes (urea, NaCl) This increases the osmolality in the vasa recta - on its way back up the medulla it has a higher osmolality than the interstitial fluid - this creates an inward osmotic gradient - water moves back into the vasa recta and solutes are secreted back into the interstitial fluid
What is the importance or UT-B
When urea is secreted into the vasa recta - it is taken up and stored in red blood cells - UT-B is required to remove it and get it back into the interstitial fluid
If UT-B mutations - Some urea is washed out of the interstitial fluid reducing the osmotic multiplication effect so the individual has problems concentrating their urine
What are the apical and basolateral membrane channel proteins for urea
UT-A1 apical UT-A3 basolateral
