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Active transport of NaCl (without
water) in the ascending limb of the loop of Henle results in an
interstitial osmolal gradient from 285 mosmol/kg (in the cortex)
to 1200 mosmol/kg in the medulla at the tip of the renal papilla.
This is facilitated by: 1) Passive absorption of water in the
descending limb of the loop of Henle, which helps to concentrate
NaCl in the tubular lumen as it enters the ascending limb and
2) Active absorption of urea from the collecting tubule under
the influence of ADH (not shown above).
In the presence of ADH (secreted in response to hypovolemia and
hyperosmolality in peripheral blood), water is absorbed (without
NaCl) in the collecting tubule into the medulla. The amount of
water absorbed is dependent on the interstitial osmolal gradient
established by the loop of Henle. Thus, urine becomes concentrated
as it equilibrates with the interstitium in the medullary collecting
tubule.
The vasa recta (blood vessels surrounding the tubules in the renal
medulla) play an important role in maintaining the osmolality
of the renal medullary interstitium. They accomplish this as follows:
1) In the vasa recta surrounding the descending limb of
the loop of Henle, NaCl is absorbed into plasma, whereas water
leaves the plasma and enters the interstitium in response to the
high interstitial sodium chloride and urea concentrations created
by the renal tubules. 2) In the vasa recta surrounding the ascending
limb, the reverse occurs because the plasma is now hypertonic
to the medullary interstitium. This results in absorption of water
into the blood and return of the absorbed solute to the interstitium.
This is referred to as the countercurrent exchange mechanism.
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Formation of medullary interstitial hypertonicity is dependent upon
the following:
- Medullary blood flow through the vasa recta: This is essential
for operation of the countercurrent exchange mechanism.
- Sodium absorption: Absorption of sodium without water in
the ascending limb of the loop of Henle is essential for formation
of the medullary interstitial osmotic gradient. The amount of NaCl
reaching this part of the tubule is dependent on GFR and the rate
of proximal tubule resorption. A decrease in GFR or increase in proximal
tubule resorption will decrease the amount of NaCl delivered to the
distal tubules, and will lower medullary hypertonicity, thus impairing
renal concentrating ability.
- Urea absorption: Absorption of urea in the collecting tubules,
under the influence of ADH, enhances the concentration gradient formed
in the medullary interstitium.
Several factors can thus influence this concentration gradient:
1) Decreased sodium absorption: This
occurs in chronic polyuria of any cause (e.g. diabetes insipidus, diabetes
mellitus) or diseases affecting sodium resorption (e.g. Addison's disease).
2) Lack of ADH: Lack of urea absorption
in the collecting duct decreases the medullary interstitial osmolality,
particularly at the base of the loop of Henle (renal papillary tips).
3) Increased medullary blood flow:
This causes medullary solute washout, because the vasa recta is critical
in maintaining the medullary interstitial gradient. Some factors which
increase medullary blood flow include hypokalemia, hypercalcemia, thyroid
hormone and long-standing polyuria.
4) Distal solute load: The rate of
solute delivery in the collecting ducts affects renal concentrating
capacity. As solute excretion increases, urine osmolality decreases.
This is thought to be due to solute diuresis enhancing renal medullary
blood flow and the rapid flow rate through the ducts, which shortens
the contact time necessary for allowing equilibration with the medullary
interstitium.
Antidiuretic hormone
ADH acts on chief cells in collecting tubules, increasing permeability
of the tubules to water and urea. ADH acts via adenylate cyclase which
opens channels in the tubules, called aquaporins, facilitating water
absorption. ADH is secreted by the hypothalamus in response to osmotic
(mainly determined by sodium) and non-osmotic (volume depletion, nausea,
fear, anxiety, pain, exercise and drugs) stimuli. Several things inhibit
the action of ADH on renal tubules and thus affect renal concentrating
ability. These include:
- Hypokalemia
- Hypercalcemia
- Corticosteroids
- Endotoxin
- Prostaglandin E
In any of the above conditions, urine concentrating ability is impaired
for reasons other than physical loss of functional nephrons. When combined
with a cause of pre-renal azotemia (eg, hypovolemia due to dehydration),
these conditions can mimic findings typical of renal failure, i.e. the
urine is less concentrated than is expected in a pre-renal azotemia
(but is usually not isosthenuric).
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