Page 46 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Applied Renal Physiology 35

if the transported substances are moving in opposite ultrastructurally the most complex and suited for the
directions across the membrane (e.g., sodium and hydro- mechanisms of solute transport described earlier. 31 This
gen ions at the luminal membrane of the proximal tubular morphologic complexity decreases along the length of
cell). The “uphill” (i.e., against a concentration gradient) the proximal tubule. In the first segment of the proximal
transport of one substance (e.g., glucose) is linked to the tubule (S1), sodium, water, bicarbonate, amino acids,
“downhill” (i.e., down an electrochemical gradient) glucose, and phosphate are transported. In the second
transport of another substance (e.g., sodium). When segment (S2), sodium, water, and chloride are
the carrier is occupied by only one of the substances, it reabsorbed, and organic acids and bases may be
is not mobile in the cell membrane, whereas an unoccu- transported. 43 Organic acids and bases may also be
pied carrier or one that is occupied by both of the secreted in the third segment (S3). 31 The low-specificity
substances is mobile in the membrane. This process is sat- transport system for organic anions and cations in the
urable, demonstrates structural specificity and affinity of proximal tubule allows elimination of many drugs and
the carrier for the substances transported, and may be other foreign organic compounds from the body.
competitively inhibited. The uphill transport occurs with-
out direct input of metabolic energy, and the substance SODIUM TRANSPORT
transported uphill is said to experience secondary active Sodium may enter tubular cells at their luminal surface by
transport. The metabolic energy for secondary active several different mechanisms. In the proximal tubule,
transport at the luminal membranes comes from the pri- sodium may be cotransported across the luminal
mary active transport of sodium out of the tubular cell at membranes of the cell with glucose, amino acids, or phos-
þ
þ
the basolateral membrane by Na ,K -ATPase, a process phate or may experience countertransport with hydrogen
þ
that maintains a low intracellular sodium concentration. ions secreted into the tubular lumen by the Na -H þ
Pinocytosis refers to the uptake by cells of particles antiporter that facilitates bicarbonate reabsorption. In the

þ
þ
too large to diffuse through the cell membrane. Filtered loop of Henle, sodium enters via an Na -K -2Cl carrier
proteins are reabsorbed in the proximal tubule by this that is competitively inhibited by furosemide, 37 and
mechanism. in the distal convoluted tubule, sodium enters via an Na þ

Solvent drag refers to the process, whereby water (the Cl cotransporter that is inhibited by thiazide diuretics.
solvent) moving across an epithelium by osmosis can drag In the collecting duct, sodium enters via a luminal sodium
dissolved solutes along with it. channel that generates a lumen-negative PD favoring
chloride reabsorption.
MORPHOLOGY OF THE PROXIMAL Thus, in most segments of the nephron, sodium enters
TUBULE the tubular cell at the luminal membrane down an electro-
Several morphologic features of proximal tubular cells chemical gradient that favors sodium entry into the cell
suggest their primary role in the reabsorption of solutes (i.e., the interior of the cell has a low sodium concentration
and water. The brush border of the luminal surface of and is negative with respect to the exterior). Sodium then
the proximal tubular cells consists of microvilli, which experiences primary active transport out of the cell and into
increase surface area, and lateral cellular interdigitations, the lateral intercellular spaces and peritubular interstitium
þ
þ
which increase the surface area of the basolateral by the Na ,K -ATPase located in the basolateral cell
membranes (Fig. 2-10). Abundant mitochondria supply membranes. This enzyme hydrolyzes ATP and translocates
energy in the form of ATP required for active transport. two potassium ions into the cell and three sodium ions out
1
The proximal tubule exhibits intrasegmental axial of the cell. It is located only in the basolateral membranes
heterogeneity with the most proximal segments being and functions to maintain a favorable electrochemical
gradient for the passive entry of sodium into the tubular
cells across their luminal membranes. Thus, sodium is
reabsorbed in conjunction with glucose, amino acids,
phosphate, and bicarbonate in the proximal tubule and
with chloride in the loop of Henle and distal tubule.
The different mechanisms for sodium reabsorption in
the nephron and the regulation of sodium reabsorption
in the kidneys are discussed in Chapter 3.
GLUCOSE TRANSPORT

Sodium attaches to a carrier in the luminal membrane of
the proximal tubular cell, and this step is followed by
attachment of glucose to the carrier. Translocation of
Figure 2-10 Three-dimensional model of a proximal tubular cell the carrier occurs, and glucose is released to the interior
showing microvilli and lateral cellular interdigitations. 31 of the cell while sodium enters down its electrochemical