Lecture 6 - Urine Concentration and Dilution Flashcards
What are the 6 ingredients to make concentrated urine?
- Loop of Henle
- Active NaCl transport in the thick ascending limb of loop of Henle
- Different permeabilities to NaCl and H2O in descending loop vs ascending limbs of the loop of Henle
- Anti-diuretic hormone
- Urea
- Low medullary blood flow
2 others names for anti-diuretic hormone?
- AVP
2. Vasopressin
Osmolarity of cortical interstitium? Why?
300 mOsm/L (aka isosmotic with plasma)
Because water and solute move together through the proximal and distal tubules
Osmolarity of medullary interstitium?
300 at cortico-medullary junction to 1200 mOsm/L at the papilla
When is the papillary intersitium osmolarity actually 1200 mOsm/L?
When the kidney is producing maximally concentrated urine, aka 1200 mOsm/L urine (4x more concentrated than blood)
Most dilute urine possible?
30-50 mOsm/L
Describe active NaCl transport in the thick ascending limb of loop of Henle.
Tubular fluid becomes HYPOtonic compared to plasma
Describe the different permeabilities to NaCl, urea, and H2O in descending loop vs ascending limbs of the loop of Henle.
DESCENDING LIMB:
- Water permeability = high
- Na+ permeability = low
- Urea permeability = low
ASCENDING LIMB:
- Water permeability = low
- Na+ permeability = high
- Urea permeability = medium
Where is ADH made? Where is it stored?
Made in hypo and stored in posterior pituitary
Effect of ADH on the kidney?
Causes kidney collecting ducts to be permeable to water: reabsorb water, decreasing urine volume and increasing its concentration
Describe urine formation through the nephron.
- Filtration at the glomerulus into Bowman’s capsule
- Proximal tubule: solutes and water reabsorbed in equal proportions and 1/3 of the volume is left
- Descending limb of the loop of Henle: osmolarity of medulla is increasing so water is reabsorbed (but not solutes: impermeable) into the vasa recta, making tubular fluid HYPERosmotic to plasma and finally equilibrates with medullary osmolarity
- Thin ascending limb of the loop of Henle: NaCl is present in higher concentrations inside the tubular fluid than in the medulla + osmolarity of medulla is decreasing so solute is reabsorbed via passive diffusion (but not water: impermeable) into the vasa recta, making tubular fluid less HYPERosmotic + some urea secreted via diffusion from the inner medullary collecting duct
- Thick ascending limb of the loop of Henle: osmolarity of medulla is decreasing so solute is reabsorbed via active transport (but not water: impermeable) in EXCESS to make urine HYPOsmotic to plasma (~150 mOsm/L)
- Distal convoluted tubule: NaCl reabsorption via secondary active transport (NO WATER)
IF ADH IS PRESENT: - Collecting duct permeable to water so water is reabsorbed both in the cortical and medullary segments AND actively transports solute (which stimulates further H2O absorption): NaCl in cortex and outer medulla and urea in inner medulla (to thin ascending limb and to vasa recta) => until urine is isosmotic with papillary medulla
- Urine excreted is HYPERtonic
IF ADH IS NOT PRESENT: - Collecting duct NOT permeable to water, but reabsorbs NaCl + collecting duct NOT permeable to urea so less water reabsorption in the thin descending limb of the loop of Henle
- Urine excreted is HYPOtonic
What portion of the nephron is termed the diluting segment?
Thick ascending limb of the loop of Henle
Is the collecting duct in the inner medulla ALWAYS permeable to urea?
NOPE - only in presence of ADH
Describe how the osmotic gradient is set up in the medulla.
- Single effect: active Na+ transport to the interstitium in the thick ascending limb of the loop of Henle is the initiating event, generating a 200 mOsm gradient and solute is trapped in between the 2 limbs
- NaCl is removed slowly in the medulla because blood flow is slow in vasa recta and is removed fast in the cortex because blood flow is fast in peritubular capillaries => a gradual gradient is created
- Descending limb of loop of Henle needs to equilibrate with the interstitium between the 2 limbs
- Collecting duct also equilibrates with the interstitium on the other side of the ascending limb of the loop of Henle
What does the range of the gradient in the medulla depend on?
- Length of loop of Henle
- Strength of the pumps in the thick ascending limb of the loop of Henle
- Permeability of nephron segments
- Impact of ADH
What is the most concentrated urine possible just based on NaCl?
600 mOsm/L (300 from Na+ and 300 from Cl-)
Where can the movement of urea be regulated in the nephron?
Inner medulla
Plasma urea concentration?
5 mEq/L
How does urea permeability in the collecting duct affect the rest of the nephron?
Act as an osmotic agent to pull water out of the descending limb of the loop of Henle
Is the proximal tubule permeable to urea?
YUP - half of it gets reabsorbed there PARACELLULARLY
Is the thin ascending limb of the loop of Henle permeable to urea?
YUP - urea actually is secreted in this portion due to the high concentration of urea in the medulla
Are the thick ascending limb and distal convoluted tubule, and cortical and outer medullary collecting ducts permeable to urea?
NOPE
What segment of the nephron is termed the urea recycling segment?
Inner medullary collecting duct
Purpose of urea being reabsorbed into the interstitium by the inner medullary collecting duct?
Increase in interstitium osmolarity to increase water reabsorption in the thin descending limb of the loop of Henle to make more concentrated urine
What happens to urea when the kidney is making diluted urine?
More of it is excreted
Once ADH starts rising, what happens to the nephron?
- Collecting duct is permeable to water and can reabsorb water
- Inner medullary collecting duct is permeable to urea and can start reestablishing the concentration gradient in the medulla for the thin descending limb of the loop of Henle
Half-life of ADH?
Seconds
Stimulus for ADH secretion to STOP?
Fall in plasma osmolarity
What is the purpose of low plasma flow rate in the medulla?
Helps preserve solute in the medulla to create concentration gradients
What % of renal blood flow goes to the medulla?
5%
Describe the counter current exchange in the vasa recta.
- As blood flow descends as isosmotic the interstitium becomes more and more concentrated, so the solutes from interstitium/ascending vasa recta flow into the plasma and water flows out
- As blood flow ascends, the interstitium osmolarity decreases, so solutes flow out to the interstitium/vasa recta and water flows back in => process of solutes and water moving from the ascending vasa recta to the descending vasa recta is called countercurrent exchange
=> Net result: net outflow of solute and volume in vasa recta matching the H2O coming out of the descending limb and solute coming out of the ascending limb of the loop of Henle
Do the vasa recta have solubility restrictions?
NOPE
What would happen if the flow through the vasa recta was higher?
More water would exit the vasa recta and the interstitium would be diluted => less water reabsorbed in the descending limb of the loop of Henle and the => less solute reabsorbed in the thin ascending limb of the loop of Henle => less water reabsorbed in the collecting duct => increase in amount of solute and water excreted
Why do we call the loop of Henle the countercurrent multiplier?
Because the small 200 mOsm/L gradient is multiplied by the length of the loop of Henle
Why do we call the vasa recta the countercurrent exchanger?
Because it is not contributing to the gradient created by the loop of Henle, it is maintaining it by having solutes and water moving from the ascending vasa recta to the descending vasa recta
Is the medulla always HYPERtonic to plasma?
YUP
At the hairpin of the loop of Henle, the osmolarity of the tubular fluid and the medulla is the same… so what is different? What is the point of this?
Interstitum: 600 mOsm/L due to NaCl and 600 mOsm/L due to urea
Tubular fluid: mostly NaCl
Driving force for NaCl to passively leave the ascending limb of the loop of Henle right away when it becomes permeable and for urea to be secreted
How much would we pee if we didn’t have ADH?
1 L/hr
What % of the GFR does the collecting duct reabsorb?
More than 10%
Which is faster: flow rate in vasa recta or flow rate in nephron?
VASA RECTA
What could increase medullary flow rate in the vasa recta?
Vasodilator
What could decrease medullary flow rate in the vasa recta?
Vasoconstrictor
What drives urea reabsorption in inner medullary collecting duct?
Half of urea reabsorbed by proximal tubule => urea secreted into thin ascending limb (back to filtered amount, but higher than plasma osmolarity because less water) => water reabsorbed in collecting duct so urea osmolarity now higher than in plasma and higher than in interstitium => urea reabsorbed
What limits dilution/concentration of urine?
Length and depth of the loops of Henle
Compared to plasma, tubular fluid entering the distal tubule is… hypo, iso, or hyper osmotic at all times?
Hypoosmotic at all times
Does active NaCl transport in the proximal tubule contribute to the formation of maximally concentrated urine?
NOPE
Does the impermeability of the thick ascending limb of the loop of Henle to water contribute to maximally concentrated urine?
YES
Is the cortical collecting duct permeable to urea in the presence of ADH?
NOPE
Which nephron segment is the primary site of water reabsorption?
PCT
Describe the osmolarity throughout the entire nephron. Which parts are affected by the presence/absence of ADH?
- Proximal tubule: isosmolar to blood
- *Loop of Henle: increases (up to 1200 with ADH and 600 without) in descending limb and then decreases back to a little less than 300 mOsm/L with ADH and 200 without it
- *Thick ascending limb: decreases to 100 mOsm/L without ADH and 250 with it
- *Late distal tubule: increases with ADH back to close to 300 and very slight decrease without (less than 100)
- *Cortical collecting duct: increases with ADH to 300 and and very slight decrease without it (less than 100)
- *Medullary collecting duct: increases to 1200 with ADH and very slight decrease without (down to 50)
In which segment is urea secreted in the nephron?
Thin ascending limb of loop of Henle
In which part of the nephron does urea concentration exceed the plasma concentration?
Hairpin turn of loop of Henle
