Dilution & concentration of urine
From Iusmphysiology
(Difference between revisions)
Line 61: | Line 61: | ||
===Steep gradient of interstitial osmolarity=== | ===Steep gradient of interstitial osmolarity=== | ||
+ | *The cortex has an interstitial osmolality of about 300 mOsm while the inner medulla osmolality is 1200 mOsm. | ||
+ | **This was determined from frozen rat sections of kidneys. | ||
+ | |||
+ | ===Kidney medulla contains two countercurrent mechanisms=== | ||
+ | *Recall that '''the whole point of the osmolarity gradient along the nephron is to allow water to flow ''down an osmolarity gradient'' across the collecting duct'''. | ||
+ | *So, the first thing to remember is that '''water only flows across the collecting duct when AVP is being expressed''' otherwise the collecting duct is impermeable to water. | ||
+ | *To understand the countercurrent mechanisms, remember that the kidney is trying to make the medulla highly filled with solute and very low on water (that is, the medulla should have a high osmolarity) so that water can flow from the filtrate (which is pretty concentrated at the collecting duct, into the medulla). | ||
+ | *Now, understand that '''the loop of henle establishes the osmolarity gradient and the vasa recta maintain the gradient'''. | ||
+ | **We say that '''the loop of henle is a countercurrent multiplier'''. That is, it puts solute into the medulla. | ||
+ | **We say that '''the vasa recta is a countercurrent exchanger'''. That is, it takes water out of the medulla. | ||
+ | |||
+ | ===Loop of Henle and countercurrent multiplication=== | ||
+ | *Recall that the whole point of the loop of Henle is to increase solute levels of the medulla. | ||
+ | *The loop achieves a high solute, low water distribution by alternating (along the descending and ascending loops) whether or not water or NaCl can escape the filtrate into the interstitium. | ||
+ | **As filtrate descends, water can escape into the interstitium but NaCl cannot follow. | ||
+ | ***Note that this escape of water might seem to balance the pumping out of NaCl, but it will be removed from the medulla by the vasa recta. | ||
+ | **As filtrate ascends, '''NaCl is actively pumped into the interstitium''' but water cannot follow. | ||
+ | *It is important to understand that NaCl is actively pumped because it is this burning of ATP that allows us to generate a gradient. | ||
+ | **Recall that without energy, nothing flows against its gradient. | ||
+ | **This active pumping is able to generate a gradient of 200 mOsm / kg between the descending and ascending filtrate; one can imagine that there is a limit to the gradient this pump can generate because of leaky channels, ATP turnover, et cetera. | ||
+ | *We call this a '''multiplication countercurrent''' because as the filtrate moves down and back up the tubule, the gradient is continually brought to a 200 mOsm difference such that the difference along the axis of the loop of Henle increases. | ||
+ | |||
+ | ===Vasa recta and countercurrent exchange=== | ||
+ | *Recall that the whole point of the vasa recta is to decrease the water levels of the medulla. | ||
+ | *Vasa recta are long, thin capillaries '''from the efferent arterioles of the juxtamedullary glomeruli'''. | ||
+ | *Recall that the loop of Henle let water enter the medulla through passive reabsorption in the descending loop. | ||
+ | *The vasa recta are the mechanism by which this water is removed from the medulla, resulting in a net gain of solute to the interstitial fluid (given all that is occurring at along the loop of Henle and the vasa recta). | ||
+ | *The '''vasa recta allow water to short circuit the path of the blood'''; that is, water will move from the descending branch of the vasa recta to the ascending. | ||
+ | **Water can short circuit the vasa recta loop because solutes can also short circuit in the opposite direction. | ||
+ | **Solutes that short circuit are said to be "cycling" because they can flow through the same stretch of vasa recta multiple times. | ||
+ | |||
+ | ===Thermal models and countercurrent exchange=== | ||
+ | *Thermal models can help demonstrate how countercurrent exchange works. | ||
+ | *Imagine a source of heat at the bottom of the medulla: | ||
+ | **As filtrate flows down the descending limb to the source of heat it will heat up. | ||
+ | **As filtrate flows up the ascending limb (right next to the descending limb) it will heat the descending fluid next to it. | ||
+ | **Since the fluid now flowing down the descending limb is being heated by the ascending fluid and by the heat source itself (through conduction), there will be an increased temperature of that fluid when it hits the bottom. | ||
+ | **An equilibrium will be reached. | ||
+ | **There will be a nice heat gradient in the descending and ascending fluid as they flow along the cortical-medulla axis. | ||
+ | ***And this gradient will generate a larger difference (larger gradient) than if one had just stuck a heat source at the bottom of the medulla and had no fluid flow. | ||
* | * |
Revision as of 20:03, 1 April 2011
Dilution and concentration of urine
Why concentrate the urine?
- The kidneys concentrate the urine in order to save water for the body.
- About 600 mOsm of solute is secreted per day.
- If this were secreted at plasma concentrations, we would secrete 2 liters of water.
- When concentrated maximally, we can secrete this much solute in 0.5 liters of water.
- So we save 1.5 liters of water / day by concentrating the urine.
Hydration state calculations
- In considering the hydration state we care about how concentrated the urine is relative to the plasma and how much urine is being produced.
- The ratio of osmols in the urine to the plasma tells us whether more solute or more water is being lost:
- Uosm / Posm describes how concentrated the urine is relative to the plasma.
- The closer to infinite the ratio approaches, the more concentrated and the more water is conserved.
- The closer to zero the ratio approaches, the less concentrated and the more water is lost.
- Concentration of the urine is expressed in osmols: Uosm
- Concentration of the plasma is expressed in osmols, also: Posm
- When Uosm / Posm > 1, solute is being lost from the blood relative to water.
- When Uosm > Posm, we call the urine hyperosmotic; that is, water would rush out of a cell if placed in this urine.
- When Uosm / Posm = 1, solute and water are being lost from the blood at equivalent rates.
- In this case, we call the urine iso-osmotic to the plasma.
- When Uosm / Posm < 1, water is being lost from the blood relative to solute.
- When Uosm < Posm, we call the urine hypo-osmotic; that is, water would rush into a cell placed in this urine.
- Uosm / Posm describes how concentrated the urine is relative to the plasma.
- The next term of interest is Cosm, that is, the clearance of osmols.
- Given our ratio of urine and plasma concentrations (Uosm / Posm), we can develop a term that describes the net clearance of osmols by multiplying the ratio by the flow rate.
- Recall that V-dot represents the urine flow rate.
- Cosm = (Uosm / Posm) * V
- Cosm describes how much solute is being excreted as a function of flow rate (V), the concentration of the urine (Uosm) and the concentration of the plasma (Posm).
- In another sense, Cosm describes how much solute is being excreted as a function of flow rate (V) and water retention / loss (Uosm / Posm).
- Cosm is directly related to flow rate: as flow increases or decreases, solute excretion increases or decreases.
- Cosm can also be elevated by increasing the concentration of the urine or decreasing the concentration of the plasma.
- This makes sense because more concentrated urine contains relatively more solute than less concentrated urine, so it will clear solutes from the plasma more rapidly (that is, result in an elevated Cosm).
- Note that the concentration of the plasma does not change often.
- Given our ratio of urine and plasma concentrations (Uosm / Posm), we can develop a term that describes the net clearance of osmols by multiplying the ratio by the flow rate.
- A mis-named term called the "free water clearance" describes how much water is removed from the plasma to generate urine.
- "Free water clearance" is denoted as CH20.
- "Free water clearance" is a misnomer because this does not really describe the "clearance" of water (as in the "clearance of aspirin").
- CH20 = V - Cosm = V - (V * (Uosm / Posm)) = V * (1 - (Uosm / Posm))
- Note that we are subtracting a portion of the flow from the flow itself.
- We know that the ratio of Uosm to Posm describes the clearance of osmols in terms of flow.
- So, to subtract the clearance of osmols from the flow gives us a term describing how much water was not cleared.
- That is, CH20 describes how much of the plasma was cleared of solute.
- When CH20 > 0, solute-free water is being removed from the plasma in order to dilute the urine.
- When CH20 < 0, solute-free water is being removed from the urine in order to concentrate the urine.
- When CH20 = 0, the urine is iso-osmotic relative to the plasma.
The long and short of Henle loops
- Species with a high proportion of long loops of henle (relative to short loops) can achieve greater urine concentration.
- Recall that long loops of henle drop deep into the medulla whereas short loops only superficially enter the medulla.
- 15% of human loops are long.
- The kangaroo rat rarely has to drink water because it has many long loops and can conserve so much of its water.
- The ability to produce osmotically concentrated urine is directly proportional to the length of the Henle loops.
- Desert dwellers have long loops, hydrated habitators have short loops.
Steep gradient of interstitial osmolarity
- The cortex has an interstitial osmolality of about 300 mOsm while the inner medulla osmolality is 1200 mOsm.
- This was determined from frozen rat sections of kidneys.
Kidney medulla contains two countercurrent mechanisms
- Recall that the whole point of the osmolarity gradient along the nephron is to allow water to flow down an osmolarity gradient across the collecting duct.
- So, the first thing to remember is that water only flows across the collecting duct when AVP is being expressed otherwise the collecting duct is impermeable to water.
- To understand the countercurrent mechanisms, remember that the kidney is trying to make the medulla highly filled with solute and very low on water (that is, the medulla should have a high osmolarity) so that water can flow from the filtrate (which is pretty concentrated at the collecting duct, into the medulla).
- Now, understand that the loop of henle establishes the osmolarity gradient and the vasa recta maintain the gradient.
- We say that the loop of henle is a countercurrent multiplier. That is, it puts solute into the medulla.
- We say that the vasa recta is a countercurrent exchanger. That is, it takes water out of the medulla.
Loop of Henle and countercurrent multiplication
- Recall that the whole point of the loop of Henle is to increase solute levels of the medulla.
- The loop achieves a high solute, low water distribution by alternating (along the descending and ascending loops) whether or not water or NaCl can escape the filtrate into the interstitium.
- As filtrate descends, water can escape into the interstitium but NaCl cannot follow.
- Note that this escape of water might seem to balance the pumping out of NaCl, but it will be removed from the medulla by the vasa recta.
- As filtrate ascends, NaCl is actively pumped into the interstitium but water cannot follow.
- As filtrate descends, water can escape into the interstitium but NaCl cannot follow.
- It is important to understand that NaCl is actively pumped because it is this burning of ATP that allows us to generate a gradient.
- Recall that without energy, nothing flows against its gradient.
- This active pumping is able to generate a gradient of 200 mOsm / kg between the descending and ascending filtrate; one can imagine that there is a limit to the gradient this pump can generate because of leaky channels, ATP turnover, et cetera.
- We call this a multiplication countercurrent because as the filtrate moves down and back up the tubule, the gradient is continually brought to a 200 mOsm difference such that the difference along the axis of the loop of Henle increases.
Vasa recta and countercurrent exchange
- Recall that the whole point of the vasa recta is to decrease the water levels of the medulla.
- Vasa recta are long, thin capillaries from the efferent arterioles of the juxtamedullary glomeruli.
- Recall that the loop of Henle let water enter the medulla through passive reabsorption in the descending loop.
- The vasa recta are the mechanism by which this water is removed from the medulla, resulting in a net gain of solute to the interstitial fluid (given all that is occurring at along the loop of Henle and the vasa recta).
- The vasa recta allow water to short circuit the path of the blood; that is, water will move from the descending branch of the vasa recta to the ascending.
- Water can short circuit the vasa recta loop because solutes can also short circuit in the opposite direction.
- Solutes that short circuit are said to be "cycling" because they can flow through the same stretch of vasa recta multiple times.
Thermal models and countercurrent exchange
- Thermal models can help demonstrate how countercurrent exchange works.
- Imagine a source of heat at the bottom of the medulla:
- As filtrate flows down the descending limb to the source of heat it will heat up.
- As filtrate flows up the ascending limb (right next to the descending limb) it will heat the descending fluid next to it.
- Since the fluid now flowing down the descending limb is being heated by the ascending fluid and by the heat source itself (through conduction), there will be an increased temperature of that fluid when it hits the bottom.
- An equilibrium will be reached.
- There will be a nice heat gradient in the descending and ascending fluid as they flow along the cortical-medulla axis.
- And this gradient will generate a larger difference (larger gradient) than if one had just stuck a heat source at the bottom of the medulla and had no fluid flow.