2020B Question 04
Describe the physiological mechanisms by which the renal collecting duct is able to produce both dilute and concentrated urine.
Examiner Report
The major domains assessed in this question were: - the mechanisms that result in presentation of a hypotonic filtrate to the collecting duct
- The role of antidiuretic hormone (ADH) in the collecting duct, including control mechanisms
- The role of medullary tonicity in the movement of water
Credit was given for other relevant correct material. The most common problem was not considering the mechanisms involved in the two scenarios posed by the question – production of both a dilute and concentrated urine. Other problems encountered included:
- Focusing on the formation and maintenance of the medullary solute gradient without relating it to the question
- Not understanding the role of ADH as the dominant mechanism for control of water movement in the collecting duct
- Not understanding how the production of ADH is controlled
- The majority of diagrams did not add to the written answer
Candidates who scored well addressed the 3 major domains being assessed and related each back to their role in formation of dilute and concentrated urine by the collecting duct.
Model Answer
Structure:
- Introduction
- Renal water handling
- Iso-osmolar reabsorption
- Countercurrent multiplication
- Urea recycling
- Countercurrent exchange
- ADH
Introduction
| Factor | Detail |
|---|---|
| Numbers | - Renal blood flow 7,200L.day-1 - Glomerular filtration 180L.day-1 - Urine output 1-3L.day-1 |
| Summary | - Iso-osmolar absorption of the majority (cortical nephrons) - Variable concentration of the remainder (juxtamedullary nephrons) - Tonicity gradient created by countercurrent multiplication and urea recycling - Tonicity gradient maintained by countercurrent exchange - Variable water reabsorption ∝ [ADH] |
Renal Water Handling
| Proportion | Mechanism | |
|---|---|---|
| Proximal tubule | 65% | - Osmosis - Gradient established by basolateral Na+K+ATPase |
| Thin descending limb of loop of Henle | 10% | - Osmosis - Gradient established by Na+K+ATPase in thick ascending limb |
| Thick ascending limb of loop of Henle | - | |
| Distal convoluted tubule | - | |
| Connecting tubule | - | |
| Collecting ducts | 5-24.7% | - Osmosis - Dependent upon creation and preservation of hypertonic interstitium - Under control of ADH |
Iso-Osmolar Absorption
| Component | Detail |
|---|---|
| Location | - Proximal tubule >> Other |
| Mechanism | - Basolateral Na+K+ATPase establishes solute gradients - Na+ reabsorption is paired with multiple osmolytes (K+, Cl-, HCO3-, glucose, amino acids) - Water follows by osmosis |
| Autoregulation | I.e. Glomerulotubular balance: - Fixed proportion (not amount) of glomerular filtrate is reabsorbed by the proximal tubule - Prevents overwhelming of loop of Henle and distal nephron - ?Due to ↑ glucose and amino acid filtration → ↑ Reabsorption paired with Na+ - ?Due to changes in oncotic pressure in the lateral intercellular space and peritubular capillaries |
Countercurrent Multiplication
| Steps | Detail |
|---|---|
| Step 1 | - Thick ascending limb is permeable to solute, not water - Filtered solute reabsorbed by 2° active transport (~25% filtered Na+/Cl-/K+) - Passage via apical Na+K+2Cl- symporter - Basolateral Na+K+ATPase creates Na+ gradient - Effects: ↓ Urine osmolality, ↑ interstitial osmolality to a level above normal |
| Step 2 | - Thin descending limb is permeable to H2O, not solute - Filtered H2O reabsorbed by osmosis (eventually 10% of that filtered) - Effects: ↑ Urine osmolality, ↓ interstial osmolality but not back to starting level |
| Steps 3+ | - Process is repeated, therefore amplified |
Urea Recycling
| Component | Detail |
|---|---|
| Urea handling | - Freely filtered - 50% reabsorbed by proximal tubule - Same 50% secreted into thin descending loop of Henle - Same 50% reabsorbed in medullary collecting ducts via ureaporins (if ADH present) |
| Mechanism | - Repeat transit between thin descending loop of Henle and medullary collecting duct - Antegrade via the urine - Retrograde via the interstitium - Multiple passages of each molecule before excretion → ↑ Interstitial osmolality |
Countercurrent Exchange
| Component | Detail |
|---|---|
| Principle | - Unidirectional rapid blood supply would cause dilution of interstitium by osmosis - Bidirectional slow flow minimizes dilution – i.e. vasa recta |
| Mechanism | - Vasa recta exist alongside juxtamedullary nephrons - Descending limb: Water lost, solute gained - Ascending limb: Water gained, solute lost - Hence minimal change to interstitium - (Note also some reabsorption into lymphatics) |
Anti-Diuretic Hormone (ADH)
| Component | Detail |
|---|---|
| Source | - Produced by supra-optic and paraventricular nuclei of the hypothalamus - Released by posterior pituitary |
| Release stimuli | - ↓ Osmolality (sensitive to ∆2%) - ↓ Blood volume (sensitive to ∆10% but overrides osmolality) - ↓ MAP - Angiotensin 2 - Stress response e.g. Surgery - Many drugs |
| Renal effects | - Insertion of aquaporin 2 into apical membrane of collecting duct → ↑ H2O reabsorption hence urine concentration - Insertion of ureaporin into apical membrane of medullary collecting duct → ↑ Urea recycling → ↑ Interstitial osmolality → ↑ Capacity for H2O reabsorption (Also ↑ Na+ reabsorption in thick ascending loop of Henle) |