Urine Concentration and Dilution

water balance

the kidneys adjust the amount of water excreted (and therefore the urine concentration) to help maintain a constant plasma osmolality and blood volume.

• water diuresis - occurs when the body water volume is high, causing the kidneys to produce a large volume of dilute urine.

• Antidiuresis - when body water volume is low, causing the kidneys to produce a small volume of concentrated urine. (The distal convoluted tubule and collecting duct will become more leaky so that we can get water back into our blood stream). Only will occur if ADH is present (hormone released by pituitary gland); ADH stimulates water being reabsorbed in our blood stream.

water transport

the kidney makes concentrated urine by driving water via osmosis from the tubule lumen into a hyper osmotic interstitium (in the renal medulla) and

the kidney makes dilute urine by pumping salts out of the lumen in tubule segments that are relatively impermeable to water.

Water transport in the proximal tubule, loop of Henle, and distal tubule is constitutive (always the same)(the tubule fluid leaves the distal tubule being hypo-osmotic relative to plasma).

Whether the final urine is dilute or concentrated depends on whether water reabsorption occurs in the collecting tubule and the collecting duct, which depends on the presence of arginine vasopressin (AVP, also called antidiuretic hormone, ADH)

Interstitial Osmolality

the renal cortex is isosmotic with plasma, but the osmolarity rises from the outer medulla to the inner medulla.

Outer medulla: high interstitial osmolarity is due to high sodium and chloride concentration, which results from sodium and chloride reabsorption by the thick ascending limb (TAL). Water cannot diffuse back and forth on the ascending part of the loop of Henle, which is why they instead pump out ions through active transport, making the outer medulla salty, so that osmosis can occur more greatly on the descending portion.

Inner medulla: high urea concentration adds to the NaCl, with about half the total osmolarity from urea and half from NaCl (so it is even more concentrated in this area).

Water reabsorption during antidiuresis

in the presence of AVP (secreted by the posterior pituitary), it stimulates the cells of the collecting duct to insert aquaporin channels into the membrane. They increase the water conductivity, which allows the water to exit the tubule into the interstitium when the interstitium has a higher osmolality. Reabsorbed solutes and water are transported back to the body via the vasa recta.

Ascending vasa recta will have the same osmolality as the interstitium around it that drives the waster reabsorption.

Water diuresis washout

No AVP - no water reabsorption in the collecting duct. Thus, the amount of water in the distal tubule remains in there until excretion. The active transport of sodium chloride in the collecting tubule causes the reabsorption of even more solutes; as a result, the fluid in the tubules at the end of the collecting duct will be very dilute (about 60 mOsm (around freshwater). Under long-term water diuresis, some NaCl and Urea becomes washed out by the high tubular fluid flow, resulting in an inner renal medulla of 500 mOsm as compared to 1200 mOsm.

Tubule fluid osmolality

TFosm/Posm is the ratio of tubular fluid osmolality to plasma osmolality.

In proximal tubule: TFosm/Posm = 1 (due to the high water permeability of the proximal tubule.

In loop of Henle:

Descending Limb: rises to greater than 3 (hypertonic; greater amount of solutes on the inside of tubule than on the outside (interstitium).

Ascending limb: tubular fluid becomes hypotonic; decreases to less than one.

However, this rise and descend is not as drastic throughout a stat of water diuresis. This is because solute washout in the inner renal medulla (lesser of a driving force) causes a decreased water concentrating ability.

By the end of the ascending limb, the tubular fluid osmolality is less than the plasma osmolality.

Distal tubule: in antidiuresis, the tubular fluid osmolality increases (as water leaves the tubule to be reabsorbed by the vasa recta), such that at the end of the distal tubule, the Tf/P is one.

In water diuresis, the tubular fluid osmolality further increases and the collecting tubule. This is due to active transport of sodium chloride OUT of the tubule, further reducing the concentration of sodium in the fluid.

Medullary collecting duct: in antidiuresis: osmolality increases largely (concentrated urine)

In water diuresis it will continue to decrease due to NaCl active transport.

Tubular Fluid Concentration by the collecting duct

the CD epithelium has three key permeability properties:

• absence of AVP, it is relatively impermeable to water, urea, and NaCl along its entire length.

• AVP increases the collecting duct water permeability along entire length

• AVP increases the urea permeability of the collecting duct (along the terminal portion)

In the first portion of CD, in the presence of AVP, water reabsorption occurs without urea reabsorption. This gradually increases the tubular fluid urea concentration.

In the presence of AVP, the latter portion of the CD is also permeable to urea, allowing water and urea reabsorption. This raises interstitial urea concentration, further contributing to water reabsorption.

Urea Recycling

net excretion is about 15% of filtered load. It leaves the collecting duct, goes into the this ascending limb, in a cycle.

Regulation by AVP

1. AVP is produced by neurons in the hypothalamus, which then transport it down their axons to the posterior pituitary, where it is released into the blood circulation.

   AVP has effects on two target organs:

2. Systemic vasculature (AVP at high concentrations causes widespread vasoconstriction - increased MAP).

3. AVP acts on the kidneys by increasing the water reabsorption by:

   1. Increasing water permeability in the CT and CD

   2. Increasing the NaCl reabsorption in the TAL, and

   3. Increasing the urea reabsorption by the late CD.

4. AVP increases CT and CD water permeability by increasing the number of AQP channels on the basolateral membrane

5. AVP enhances urea permeability of the terminal two thirds of the CD by stimulating activity of apical and basolateral urea transporters (water will then follow)