Page 48 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Applied Renal Physiology 37

epithelium. Thus, less urea is reabsorbed at higher tubu- medullary interstitium via UT-A1 and UT-A3 under the
lar flow rates. With decreased tubular flow, as occurs dur- influence of ADH. Reabsorbed urea enters the ascending
ing dehydration, there is increased reabsorption of water (venous) vasa recta and then is transferred to the
from the tubular fluid. This increases the concentration descending (arterial) vasa recta, which express UT-B.
gradient of urea across the tubular epithelium and This recycling of urea prevents the osmotic diuresis that
increases passive urea reabsorption. In dehydrated would occur if this urea load were excreted in the urine.
patients, increased reabsorption of urea may lead to an Knockout mice lacking UT-A2 do not have a reduc-
increase in blood urea nitrogen (BUN) even before tion in medullary urea concentration or decreased urinary
GFR is decreased. This contributes to the observation concentrating ability when fed a normal protein
that the BUN/creatinine ratio tends to be higher in diet, whereas knockout mice lacking UT-B do have
patients with prerenal azotemia than in hydrated patients decreased medullary urea concentration, as well as
with primary renal azotemia. decreased urinary concentrating ability and higher
The renal handling of urea plays an important role in BUN concentrations. 15 These results suggest that coun-
the urinary concentrating mechanism (see role of urea tercurrent exchange of urea between the ascending
in The Urinary Concentrating Mechanism section). (venous) vasa recta and descending (arterial) vasa recta
Discovery of facilitated urea transporters (UT-A and is more important for urea trapping in the inner medulla
UT-B) in the kidneys has enhanced understanding of urea than is transfer of urea to the thin descending limbs of
recycling and called into question the “passive model” of Henle’s loop.
urinary concentration. 15,49,54 Vasopressin (ADH)- THE URINARY
responsive urea transporters UT-A1 and UT-A3 in the
inner medullary collecting duct facilitate urea reabsorp- CONCENTRATING
tion and concentration in the interstitium, where it theo- MECHANISM
retically serves as a stimulus for passive NaCl reabsorption
from the thin ascending limb of Henle’s loop. According Urinary concentration is a function of the juxtamedullary
to the “passive model” of urinary concentration, 30,48 nephrons with long loops of Henle that penetrate deep
knockout mice lacking UT-A1 and UT-A3 should have into the renal medulla. There are two main steps in this
impaired ability to concentrate NaCl in the inner process. First, transport of sodium chloride without water
medulla, but this does not appear to be true. Such mice from the ascending limb of Henle’s loop renders the
have lower urea but not lower NaCl concentrations in medullary interstitium hyperosmotic. Second, vasopres-
the inner medullary interstitium, a finding inconsistent sin (ADH) increases the water permeability of the
15
with the “passive model. ” collecting duct, and tubular fluid traversing this segment
Urea reabsorbed from the inner medullary collecting of the nephron equilibrates osmotically with the
duct via AT-A1 and AT-A3 can reenter the thin hyperosmotic interstitium.
descending limb of Henle’s loop via UT-A2 and be car- Strikingly different transport properties of various
ried back to the collecting duct. This urea is concentrated portions of the nephron form the basis for understanding
in the collecting ducts as water is reabsorbed, setting the the urinary concentrating mechanism (Table 2-2). The
stage for urea to be reabsorbed again back into the inner hairpin configuration of Henle’s loop is the anatomic

TABLE 2-2 Differential Permeability Characteristics of Nephron Segments

Portion of Nephron NaCl Urea Water (ADH) Water (No ADH)

Descending limb of Henle’s loop * Passive Passive { Passive Passive
Thin ascending limb of Henle’s loop * Passive Passive { 0 0
Thick ascending limb of Henle’s loop Active 0 0 0
Distal convoluted tubule Active 0 0 0
{
Cortical collecting duct Active 0 Passive 0
Outer medullary collecting duct 0 0 Passive 0
}
Inner medullary collecting duct Active Passive Passive 0
Modified from Rose BD. Clinical physiology of acid-base and electrolyte disorders. New York: McGraw-Hill, 1994: 112, with permission of the McGraw-Hill
Companies.
*Permeability to NaCl exceeds permeability to urea in these segments.
{
Passive reabsorption in these segments is facilitated by presence of urea transporters (UT-A2) and constitutes urea recycling.
{
Responsive to aldosterone.
}
Permeable to urea in the basal state and permeability increased by ADH-responsive urea transporters (UT-A1, UT-A3, and possibly UT-A4).