Urine Flashcards
Concentration & Dilution Machinery
- Loop of Henle generates gradient of osmotic P in cortex-medulla. Cortex isotonic w/ blood plasma but medulla is hypertonic. Transports salt into interstitium & delivers dilute urine to DT & CD.
- blood flow through vasa recta acts to remove H2O from medulla, maintains solute [] @ high levels. Gradient is preserved!
- Gradient of osmotic P by medulla interstitium provides F drive for H2O reabsorption from CD.
Medullary interstitium= 1400 mOsm/L
Cortical interstitium= 300 mOsm/L
Counter current multiplication
Cortico-medullary gradient of Osmotic P
Solute [] diff of 200 b/t descending & ascending limb
- descending limb, H2O leaves tubule by osmosis
- in thin ascending limb, salt exits the tubule by diffusion as fluid encounters regions of decreasing salt content but (due to low H2O perm), H2O doesn’t follow- so tubule fluid becomes diluted.
- in thick ascending limb active transport of salt supplement passive exit from thin limb so fluid exiting it & entering DCT is hypotonic wrp to plasma!
papillary tip= 1400 mOsm/L
Long Looped Nephrons
Greater proprotion, greater [] ability of kidney
Humans have 15% LLN - can concentrate urine 5x plasma!
Medullary Interstitial Hypertonicity
Papillary [NaCl] is 350 mMx 2= 700! Other 700 made up by urea for total of 1400 mOsm/L!
Urea Permeability of loop & distal nephron
Urea medullary recycling- depends on relative permeability of diff seg of distal nephron to urea
- inner medullary descending & ascending limb have higher perm to urea than outer medullary descending limb
- perm of outer medullary & cortical ascending limbs, distal tubule & cortical collecting duct low
- no reabsorption in distal tubule & cortical collecting duct
- inner medullary collecting duct is major site of urea reaborption
Urea Recycling in Medulla
Reabsorption of urea by medullary collecting occurs through urea transporters UTs
Reabsorption by medullary CD contributes to high urea [] in medulla interstitial fluid
Interstitial [] provides F drive for urea secretion (more UTs) into loop
- No reabsorption by DT or CCD, urea secreted into loop retruns to medullary CD where part of it reabsorbed again!
urea recycles b/t CD & loop. Urea excretion 1/2 of filtered, remained in medullay hypertonicity.
Balance need to excrete sufficient urea so as to preserve plasma urea [] while maintain hypertonic medullary interstitium.
Vasa Recta
Preserve cortico medullary gradient
Blood flow to medulla is low in comparison to cortex. Flow must be low enough to maintain gradeint but fast enough to maintain supply O2 & nutrients to medulla.
Function as counter current exchange sys
- dir of blood flow in descending limb opp to ascending limb
- endothelium of capillaries highly perm to H2O & solute
As blood flows into medulla, []. Solute enters & H2O leaves. In ascending limb, H2O enters & Salt leaves.
Overall action is that solutes accum in medulla but H2O is removed.
Small amt of solute is removed as blood flows through medulla, so blood is slightly hypertonic when exits.
Faster flow= more solute removed & C-M gradient decreases
H2O Reabsorb
Proximal & distal nephron diff H2O perm!
PCT inherently high H2O perm, H2O moves out of tubule w/ solute.
Osmolar amts of solute & H2O movement equivalent, no signif osmotic gradient b/t PCT & plasm.
Reabsorption is therefore termed isotonic
Like prox tubule, thin descending limb has high perm to H2O.
As fluid moves down descending limb into medulla, H2O leaves tubule due to increase P.
Tubular fluid [] * hypertonic @ bottom of loop
Cells of distal nephron extremely low H2O perm.
- if CD H2O perm is low no further H2O movement occurs
- If CD H2O perm increased, H2O leaves CD in response to hypertonic medullary interstitium.
ADH
Increase H2O perm in cortical & medullary portions of CD
Acts in CCT, OmCD, IMCD!
ADH
Final urine [] determinant
W/o ADH, hypotonic fluid entering DCT remains so until goes through CD
Cannot equilibrate w/ hypertonic interstitium bc H2O perm is 0!
We excrete large vol of dilute urine (diuresis)
W/ ADH- H2O perm of CD increased. H2O cross eptih & equilibrate w/ hypertonic interstitium & removed by vasa recta & returned to systemic circulation
We excrete small vol of [] urine (antidiuresis)
In inner medullary CD, ADH also increase urea reabsorp- further increase urea recycle in medullary interstitium & increasing Fdrive for H2O equilibration
Cell actions of ADH
ADH binds to V2 R in basolateral mem of principal cells.
R binding activate Gs & stimulates adenylate cyclase to generate cAMP.
cAMP activates PKA which P other proteins that play a role in trafficking of intracell vesicles containing AQP2 & fusion of vesicles w/ apical mem increasing theri density @ apical end
Low ADH, AQP2 H2O channels mainly in intracell vesicles just beneath apical mem in structures called aggregophores (aggregates of AQP2 proteins)
When ADH levels in blood fall, endocytosis retrieves H2O channel aggregates from apical end & shuttle to vesicle pool
H2O exits PCs through diff mem of aquaporin family not reg by cAMP!
Osmolarity of Final Urine
Hypotonic fluid delivery to CD, alteration of fluid allows variable equilib of H2O across CD w/ medullary interstitium
If H2O perm is low, H2O excreted (diuresis)
If H2O perm is high, H2O reabsorbed (antidiuresis)
ADH Effects on Tubular Fluid Osmolarity
Water Restrition, kidneys max [] urine & excrete min vol of H2O (anti diuresis)
Ingestion of Excess H2O, causes kidneys to produce large vol of dilute urien (H2O diuresis)
Tubule fluid doesn’t change in osmolality along PT & still becomes hyptonic to plasma by end of thick ascending limb. Fluid entering DCT always hypo-osmotic wrt plasma regardless of final urien osmolality!
Under restricted H2O intake (hydropenia), elevated ADH increase H2O perm of nephron from CCD to end of IMCD. As result, osmolality of tubule fluid increases.
In CDs, luminal osmolarity rises sharply as tubule fluid equilibrates w/ surrounding medullary interstitium which becomes increasingly more hyperosmotic b/c ADH stimualtes urea reabsorption by medullary CDs
Eventually tubule fluid reaches omolarities 4-5x higher than plasma. MCDs responsible for [] final urine & highets osmotic P of tubular fluid in presence of ADH is there.
ADH loss of H2O not solute
ADH control pure H2O excretion not solute
Urine somolarity changes in reciprocal f so total solute excretion=!
