Producing a Concentrated or Dilute Urine Flashcards
What is the osmolarity of the ECF as it enters the kidney ? Describe changes in this osmolarity as it progresses through the tubules.
Normal osmolarity of the extracellular fluid is 300 mOsm/L when entering the kidney.
This is reduced to about 100 mOsm/L by the time the fluid enters the distal convoluted tubule due to reabsorption of ions.
This osmolarity is further reduced in the DCT and collecting ducts as there is additional reabsorption of sodium chloride. In the absence of ADH this portion of the tubule is also impermeable to water and the tubular fluid becomes even more dilute to as low as 50 mOsm/L.
What is the main determinant of the relative proportions of ions and water in urine ?
Kidneys have a large capacity to vary the relative proportions of ions and water in urine in response to the hydration status of the body.
What is the result of the failure to reabsorb water and continued reabsorption of ions ?
The failure to reabsorb water and continued reabsorption of ions leads to a large volume of dilute urine.
Describe renal tubular transport in a fully hydrated subject.
PT actively reabsorbs most of NaCl in water, as well as water itself so osmolality of tubular fluid stays much the same, about 300.
In Thick Descending and Thin Descending limbs of loop of Henle, as go down into interstitium in medulla,
interstitium concentration of solutes (esp NaCL) is increased. In thin DL, permeable to H2O but not to NaCl, so H2O is transported out into interstitium. Osmolality now 600.
In Thin Ascending and Thick Ascending limbs of loop of Henle, permeable to NaCl but not water. Passive movement of NaCl into interstitium, then active reabsorption (into interstitium) of NaCl in the Thick Ascending limb. These cause high concentration of NaCl in interstitium (high osmolality of NaCl in interstitium). Osmolality of tubular fluid on the other hand is down to 100 after thick ascending limb.
In DCT, CT, and CD, still possibility of active transport of NaCl, so can still extract more. These are impermeable to water, unless presence of ADH. So continuously remove Na. Overall result is very dilute urine with very low osmolality (retain most of the salts).
Why might it be necessary to make concentrated urine ?
- The ability to make and excrete urine that is more concentrated than plasma is essential for survival.
- This allows conservation of water especially when water intake is limited.
What is maximum osmolality of urine ? What conditions must be fulfilled for this to happen ?
- The human kidney can make urine up to a maximum of 1200-1400 mOsm/L which is 3-4 times that of the plasma.
- For this to happen there needs to be a high level of ADH that allows the distal tubules and collecting ducts to become permeable to water and so reabsorbed + needs a gradient to pull this water out so there needs to be a high osmolarity of the renal medullary interstitial fluid
Identify the main factors that contribute to the build- up of osmolarity in the medulla.
- Passive absorption of ions across the epithelia of the thin ascending limb of the Loop of Henle
- Active transport of sodium ions and co-transport of potassium, chloride and other ions out of the thick portion of the ascending limb of the loop of Henle.
- Active transport of ions from the collecting duct.
- Facilitate diffusion of urea from the medullary poryion of the collection ducts into the medullary interstitium.
- Diffusion of only small amounts of water from the medullary tubules into the medullary interstitium and far less than the reabsorption of ions that occurs there. This sets up an osmotic imbalance and gradient.
Describe the presence of active NaCl transport in the following:
PT Thin Descending Limb Thin Ascending Limb Thick Ascending Limb DT Cortical Collecting Tubule Inner Medullary Collecting Duct
PT: ++ Thin Descending Limb: 0 Thin Ascending Limb: 0 Thick Ascending Limb: ++ DT: + Cortical Collecting Tubule: + Inner Medullary Collecting Duct: +
Describe the permeability to H2O in the following:
PT Thin Descending Limb Thin Ascending Limb Thick Ascending Limb DT Cortical Collecting Tubule Inner Medullary Collecting Duct
PT: ++ Thin Descending Limb: ++ Thin Ascending Limb: 0 Thick Ascending Limb: 0 DT: + ADH Cortical Collecting Tubule: + ADH Inner Medullary Collecting Duct: + ADH
Describe the permeability to NaCl in the following:
PT Thin Descending Limb Thin Ascending Limb Thick Ascending Limb DT Cortical Collecting Tubule Inner Medullary Collecting Duct
PT: + Thin Descending Limb: + Thin Ascending Limb: + Thick Ascending Limb: 0 DT: 0 Cortical Collecting Tubule: 0 Inner Medullary Collecting Duct: 0
Describe the permeability to urea in the following:
PT Thin Descending Limb Thin Ascending Limb Thick Ascending Limb DT Cortical Collecting Tubule Inner Medullary Collecting Duct
PT: + Thin Descending Limb: + Thin Ascending Limb: + Thick Ascending Limb: 0 DT: 0 Cortical Collecting Tubule: 0 Inner Medullary Collecting Duct: ++ ADH
Describe renal tubular transport in a dehydrated subject.
Descending Limb: impermeable to salt, water moves passively (through aquaporin 1 channel)
Interstitial salt conc. increases as move towards hairpin bend because it is actively pumped out of the tubule (such that tubular fluid osmolality now at 1200, from 300 at PT)
Longer the loop, the more conc.
Thin ascending: Only found in long loops. Passive Na+ movement out of the tubule, no H2O movement (
Thick ascending: Active pumping against Na+ gradient, no H2O movement
Tubular fluid leaving the loop of Henle into the DCT is about 100 mOsm/L.
Distal Convoluted Tubule: DCT continues to remove ions due to active transport of sodium chloride and so the osmolarity of the tubule fluid continues to fall
Collecting tubule: H2O can move only if ADH present (in the presence of ADH the absorbed water is rapidly transported out of the kidney)
Describe the counter current mechanisms.
• The loop of Henle tubular counter-current multiplier actively generates a concentration gradient being greater the deeper into the medulla you go.
- Step 1. Fluid enters the loop of Henle from the PCT at 300 mOsm/L. The same as plasma.
- Step 2. Active transport of ions from the thick ascending limb establishes a 200 mOsm/L gradient between the tubular fluid and the interstitial fluid. 400 mOsm/L occurs in the medullary interstitium compared to 200 mOsm/L in the ascending tubule fluid.
- Step 3. The tubular fluid in the descending limb now equilibrates with the interstitial fluid as water moves out of the descending limb into the medullary interstitial fluid. Continued transport of ions but not water in the ascending limb maintains the gradient
- Step 4. Flow of fluid into the loop of Henle from the PCT moves the fluid in the limbs on. The hyperosmotic fluid in the descending limb moves on into the ascending limb.
- Step 5. Additional ions are pumped out of the fluid from the ascending limb until a 200 mOsm/L gradient is again established between the ascending limb tubule fluid and the medullary interstitium. This time the interstitial osmolarity rises to 500 mOsm/L and the ascending tubule falls to 300 mOsm/L.
- Step 6. There is again a movement of water out of the descending limb of the loop of Henle to reach osmotic equilibrium with the medullary interstitial fluid. This increases the osmolarity of the tubule fluid in the descending limb up to 500 mOsm/L which moves on into the ascending limb for the processes of sodium and other ions movement to continue.
- Steps 4-6 are repeated over and over until the net effect is that the osmolarity of the deepest part of the medulla rises to 1200 to 1400 mOsm/L.
• Blood becomes more hypertonic as it descends into the medullary interstitium (1200 at peak) and then becomes less hypertonic (300) as it ascends back towards the cortical regions.
Describe the impact of ADH in the production of a concentrated urine.
- In the cortical section of the collecting ducts the amount of water that is reabsorbed from this dilute urine is dependent on ADH levels.
- In the presence of ADH the absorbed water is rapidly transported out of the kidney by the large blood flow through the kidney cortical peritubular capillaries.
- This water absorption in the kidney cortex rather than the medulla helps preserve the osmotic gradient in the medulla.
- As the fluid continues through the collecting duct and through the medulla there is more water reabsorption into the medullary interstitium.
- Not a lot compared to that in the kidney cortical region and this water is carried away by the vasa recta into the venous supply.
- When high levels of ADH are present the collecting ducts become permeable to water and the fluid at the end of the collecting ducts is the same osmolarity as the renal medulla- about 1200 mOsm/L.
- Thus by reabsorbing as much water as possible the kidneys can produce a concentrated urine.
Describe how the permeability of urea changes in the tubule.
- Normally in the PCT 40-50% of filtered urea is reabsorbed but the concentration of urea in the tubular fluid still increases as this reabsorption is less than that of water.
- In the descending section of the loop of Henle the urea concentration continues to rise due to further water reabsorption into the medullary interstitium and the movement of urea from the medullary interstitial fluid back into the tubule (both passive and active secretion).
- The next sections of the nephron in the cortical region, the thick ascending limb, the DCT and cortical collecting ducts, are all relatively impermeable to urea so urea does not move back into the tubule fluid.
- The presence of ADH and the further reabsorption of water from these cortical tubule sections results in further increases the urea concentration of the urea already in the tubule.
- As the tubular fluid moves on into the medullary collecting ducts even more water is absorbed and the urea becomes even more concentrated.
- This high concentration of the urea causes it to diffuse out of the medullary collecting ducts into the medullary interstitial fluid.
- This is facilitated by specific urea transporters. One of these transporters is activated by ADH so enhancing the movement of urea out of the medullary collecting duct into the medullary interstitial fluid
- A moderate amount of this urea can move back into the tubule at the inner medullary section of the Loop of Henle and so can recirculate through the tubule distal to this part of the nephron several times.
- This recirculation can contribute to the concentration of urea in the distal tubular fluids in times of dehydration.
- The urea recirculation also provides an additional mechanism for the formation of the hyperosmotic renal medulla.
- In full hydration where water is to be lost then tubular flow is greater and this recirculation of urea is less marked and contributes less.
OVERALL, Urea can contribute to the osmolarity of the medullary interstitial gradient when the kidney needs to form maximally concentrated urine in dehydration.
