Formation Of Dilute And Concentrated Urine Notes

-Water intake = 2500ml/day, fluid intake, food metabolism, 1000ml/day lost in sweat, faeces at airways, remainder lost in urine

-Abnormally high water intake : DIuresis= water loss large volume of dilute hypotonic urine, 20L/day, 50mOsm/L

-Abnromally low water intake: Anti-diuresis = water conservation small volume of concentrated, hypertonic urine, 0.5L/day, 1200Osm/l

-Switch between the two states in ADH released in hydropenia-acts on the collecting ducts-water reabsorption

-average conditions of water and solute intake- 600mOsmol is dissolved in a daily urine output of 1500ml

Proximal tubule

-Default is to produce dilute urine but under prescence of hormones can become more concentrated

-Proximal tubule-reabsorbs 2/3^rd of the filtered fluid isomotically-high water permeability

Loop of Henle

Concentration of urine occurs in Loop of Henle of juxtamedullary nephrons

-Loop of Henle-differential permeabilities to water-acts as a counter current multiplier system- reabsorbs salt in excess of water, creates a hypertonic interstitium in renal medualla, -this generates an osmotic gradient in the collecting ducts, Hypotonic urine enters the collecting duct- Evidence:: Longer the loop the more concentrated the urine

The Loop of Henle is known as a countercurrent multiplier because it is able to multiply the transverse gradient of 200mOsm at each point into an axial gradient of about 900mOsm: - forms a hyperosmolar itnerstituim that increases from 300mOsm/L in interstitium of outer medulla to as much as 1200 mOsm at renal papilla

Starting conditions- isosmotic fluid- 300 mOsm throughout the ascending and descending limbs and in the interstituim

a) Step 1-single effect

-Thick ascending limb, impermeable to water, moves NaCl from lumen out to interstitium using combination of transcellular and paracellular mechanisms

DRAW DIAGRAM IN EXAM

-Transcellular: Na+, Cl- taken up through the apical Na/K/Cl cotransporter NKCC2- couples the inward movement of 1Na+ , 1K+, 2CL- in electroneutral process driven by downhill concentration gradient of Na (set up Na-K pumps) ad Cl- , ions are exported into blood using Na-K pumps and Cl- channels

-There is no net uptake of K+ channels, as they are transported out of the apical membrane through ROMK channels- ‘Renal outer medullary Pottasium channels’, also potassium channels on the basolateral membrane-

Bartter Syndrome, the NKCC gene is mutated, which reduces uptake of sodium in TALH- Salt washing, polyuria, hypokalaemia. Secondary aldosteronism due to tubuloglomerular feedback mechanisms (decreased uptake by macular densa cells) This causes expression of aldosterone and leads to hypokalemia, which has many associated symptoms including fatigue and dysrhythmias.

-Paracellular transport: Mg2+, Ca2+

Hyperosmolar interstitium instantaneously equilibriates with lumen of descending limb- due to the high water permeability no permeability to solutes- increase in osmolarity in the tubular fluid of the descending limb

-The reabsorption of NaCl creates a 200mOsm difference between ascending limb and the combination of interstituim and descending limb- osmolaltiy of ascending limb falls to 200mOsm wheras the osmolaltiy of the interstituim and descending limb rise to 400mOsm

b) Step 2: Axial shift

-Shift of new isosmotic fluid from the proximal tubule in the cortex into the descending limb pushes the colum of tubules fluid along the loop of Henle- this leads to decrease in osmolaltiy at the top of the descending limb and increase in osmolaltiy at the bottom of the ascending limb

-The high concentration of NaCl in the lumen as the thin ascending loop is due to concentrating of NaCL in the thin descending limb- high water permeability, due to high expression of aquaporins 1, it has low permeability to NaCl, finite urea permeability

-Thin ascending limb also contributes to hypertonicity in the interstitium due to passive paracellular movement of Na+ and Cl- Thin ascending limb, thin cells, paucity of mitochondria- impermeable to water but permeable to NaCl- movment of NaCl – passive process- concentration of NaCl in the lumen exceeds that of the interstitum of the inner medulla

-Paracellular- Lumen positive transepithelial voltage drives Na+ from lumen to blood through tight junctions

2^nd cycle

-Net NaCl transports out of the ascending limb again generates an osmotic gradient of 200mOsm

-After axial shift of tubule fluid and instantaneous equilibriation of descending limb with the interstituim- osmolaltiy at the bottom of the ascending limb exceeds that of the preceding cycle

-With successive cycles- interstitial osmolality at tip of loop of Henle rises progressively from 300 to 400 to 500 to 550 and then 600

Longitudinal gradient

-The Na Cl transport from the ascending limb to the interstituim, causing hyperosmolarity in the intersituim-supply of Na, Cl- inside the ascending limb decreases as ultrafiltrate proceeds towards the cortex, less and less Na, Cl- available for transport- so interstitial concentration decreases closer to cortex- corticopapillary gradient

-There is an establishment of corticopapillary interstitial osmotic gradient- as blood flow decreases from the cortical regions to the papillary regions, less NaCl is removed and leads to an accumalation

Another factor contributing to medullary interstituim hyperosmolarity

-Urea comes from protein breakdown in the liver and contribution to medullay hyperosmolaltiy is larger with protein rich diets

-Urea is filtered into the renal tubule by the glomerulus – about half is reabsorbed in the proximal tubule

-In maximal AVP-tubule fluid...

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