Module 2 Lecture 5

Solute concentration of body fluids (ECF; plasma & interstitial spaces) is maintained at ~300mOsm (concentration of solutes per kg of water; isotonic)

This prevents cells from swelling (hypotonic) or shrinking (hypertonic) due to osmotic movement of water

Kidneys adjust to variations in fluid intake & loss by changing urine concentration & volume – Dehydration –> kidneys produce a small volume of concentrated urine – Overhydration –> kidneys produce a large volume of dilute urine

Nephrons create vertical osmotic gradient in renal medulla interstitial fluid –> to produce urine of varying concentration as required

Fluid flows in opposite directions of adjacent segments of the same tube

interaction between flow of filtrate through ascending & descending nephron limbs establishes the gradient

flow of blood through ascending & descending portions of vasa recta preserves the gradient

Countercurrent mechanisms establish & preserve the osmotic gradient from the cortex to medulla

memorize them Vivienne

It has 2 key benefits 1. Establishes a vertical osmotic gradient in the interstitial fluid, which is then used by the collecting duct to make more concentrated urine (dehydrated, regulated by ADH) 2. Dilute filtrate entering distal tubule & collecting duct allows kidneys to excrete dilute urine when needed (overhydrated)

20% filtered water enters distal & collecting tubules for ‘variable’ water reabsorption

For water reabsorption to occur: 1. An osmotic gradient needs to exist between tubule & interstitial fluid 2. Distal & collecting tubules need to be permeable to water, which is regulated by anti-diuretic hormone (ADH)

With maximal ADH, 99% water in filtrate is reabsorbed & returned to blood

ADH released by posterior pituitary upon ↑ ECF concentration • Acts on distal & collecting tubule cells to promote insertion of aquaporins in apical membrane

Dehydrated with maximal ADH: distal & collecting tubules permeable to H2O - Small volume of concentrated urine excreted (up to 1200 mOsm/L); reabsorbed water picked up by peritubular capillaries

overhydrated with NO ADH: distal and collecting tubules impermeable to water - Large volume of dilute urine excreted (as low as 100 mOsm/L) no water reabsorbed in distal nephron so excess water excreted as urine

nephrons create the vertical osmotic gradient - countercurrent multipliers

Vasa recta preserve the vertical osmotic gradient

Distal and collecting tubules use the vertical osmotic gradient to adjust urine concentration

Urine contains high amounts of water (95%), waste products (urea & creatinine) + variable amounts of other substances à useful substances “conserved” by the body

Plasma clearance: Kidneys clean or “clear” the plasma flowing through them. This is the volume of plasma completely cleared of a substance by the kidneys per minute

Clearance rate of a substance (ml/min) = Urine concentration of substance (mg/ml urine) Urine flow rate X (ml/min)/ Plasma concentration of substance (mg/ml plasma)

A substance that is freely filtered, but not reabsorbed or secreted is equal to the glomerular filtration rate (GFR), which can be ‘measured’ using exogenous inulin or ‘estimated’ using endogenous creatinine

serum creatinine (calculate eGFR), blood urea nitrogen (BUN)