L9 Renal Concentrating Mechanism

Question 1

human kidney can dilute urine ___-fold (to about ___ mOsm/L) but can concentrate it by only about ___-fold (to about ___ mOsm/L)

Answer 1

human kidney can dilute urine 10-fold (to about 30 mOsm/L) but can concentrate it by only about 4-fold (to about 1200 mOsm/L)

Question 2

high water permeability in:
- ______
- ______ when ADH is present

mechanism of water transport:
- follows the ______ model
- water permeates primarily through ___
- measurement possible in vivo by the ___ ___ technique

Answer 2

high water permeability in:
- S1, S2, and S3 segments of the proximal tubule
- Cortical Collecting Duct (CCD) and Medullary Collecting Duct (MCD) when ADH is present

mechanism of water transport:
- follows the Curran and MacIntosh model
- water permeates primarily through aquaporins
- measurement possible in vivo by the split droplet technique

Question 3

aquaporins
- structure: ___ ___; each subunit has ___ membrane-spanning segments. 1 subunit is ___
- function: ______
- not permeable to ______
- blocked by ___, reacting with ___ residues in the pore
- AQP1 (initially ___): in ___ and ______
- AQP2: on ___ membrane of the ___, is responsible for ___-regulated water permeability

Answer 3

aquaporins
- structure: functional tetramer; each subunit has six membrane-spanning segments. 1 subunit is glycosylated
- function: increases water diffusion across lipid bilayer by ~8x
- not permeable to ions or small solutes like urea
- blocked by HgCl2, reacting with cysteine residues in the pore
- AQP1 (initially CHIP28): in RBC and both apical and basolateral membranes of proximal tubule cell
- AQP2: on apical membrane of the CCD, is responsible for ADH-regulated water permeability

Question 4

countercurrent multiplier system essential to? mechanism?

Answer 4

• essential to generate the corticomedullary osmotic gradient
• “single effect”: longitudinal concentration difference of ~200 mOsm/L repeated to get a difference of ~900 mOsm/L

mechanism:
thick ascending limb:
- reabsorbs Na⁺ actively
- impermeable to water
→ hypoosmotic fluid enters the distal tubule (if little to no reabsorption occurs after this point: urine flow rate 15% of GFR)
descending limb:
- permeable to water
- fluid becomes increasingly concentrated
→ transepithelial concentration difference (between thick ascending limb and descending limb ) ~ 900mOsm/L
=> countercurrent multiplication creates a longitudinal gradient from cortex to papillary tip (~900 mOsm/L)
final urine osmolality = osmolality of ISF at the tip of the renal papilla

Question 5

countercurrent exchanger system mechanism? blood entering vs exiting vasa recta characteristics?

Answer 5

• preserves the osmotic gradient without active transport
• vasa recta serve as passive exchangers
• blood entering descending vasa recta: low osmolality, water moves out, solutes diffuse in
• blood exiting ascending vasa recta: high osmolality near the tip, solutes diffuse out, water moves in
• efficiency depends on low blood flow; increased medullary blood flow “washes out” the gradient

Question 6

role of urea in urinary concentration

• Blood Urea Nitrogen (BUN) = ___ ___concentration: ___-___ mM

reabsorption? (2)

mechanism?
- permeability stimulated by ___ in the ___ ___
- urea recycles within the ___, contributing to interstitial ___osmolarity

clinical relevance
- plasma urea:creatinine ratio: indicates ______

Answer 6

role of urea in urinary concentration

• Blood Urea Nitrogen (BUN) = urea plasma concentration: 3-9 mM

reabsorption:
- proximal tubule (S3 segment)
- inner medullary collecting duct (MCD)

mechanism
- reabsorbed down its concentration gradient after water is absorbed
- permeability stimulated by ADH in the inner MCD
- urea recycles within the medulla, contributing to interstitial hyperosmolarity

clinical relevance
- creatinine is filtered but not reabsorbed: its clearance estimates GFR
- plasma urea:creatinine ratio: indicates effective blood volume and renal perfusion