Page 47 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

36 APPLIED PHYSIOLOGY

gradient (the interior of the cell is negative and its sodium PHOSPHATE
concentration is low). As the intracellular glucose con- The uptake of phosphate into the proximal tubular cell is
centration increases, glucose leaves the cell by facilitated
similar to that of glucose in that it is coupled to sodium
diffusion across the basolateral cell membranes. The
entry at the luminal membrane. The phosphate
þ
Na ,K -ATPase in the basolateral membranes continues
þ
transporters NaPi-IIa and NaPi-IIc are responsible for
to remove sodium from the cell, thus maintaining a favor- 3
luminal entry of phosphate in the proximal tubule. An
able electrochemical gradient for sodium entry and
important distinction from glucose transport, however,
expending the metabolic energy required for glucose
is that the T max for phosphate is low and readily exceeded
transport. Luminal uptake of glucose is mediated by at
as plasma phosphate concentration increases. Hormones
least two transporters, a high-capacity, low-affinity trans- also alter the T max for phosphate, notably parathyroid
porter (SGLT2) present in the first portion of the proxi- hormone (PTH). PTH decreases the T max for phosphate
mal tubule (S1 and S2) and a low-capacity, high-affinity and increases renal phosphate excretion. Thus, the
transporter (SGLT1) later in the proximal tubule (S3). 53
kidneys, acting in concert with PTH, serve as regulators
Glucose transport meets the criteria for carrier-
of the plasma phosphate concentration.
mediated transport in that it is a saturable process. Plot-
ting the amount filtered (P x GFR), the amount AMINO ACIDS
excreted (U x V), and the amount handled by the
The proximal tubular reabsorption of amino acids is also
tubules (T x ) for a substance against the plasma concentra-
coupled to luminal sodium uptake. The T max values for
tion of that substance (P x ) yields a renal titration curve
the different groups of amino acids are very high, and
and allows determination of the renal threshold (plasma
99% of the filtered load of amino acids is reabsorbed in
concentration at which the substance first appears in
the urine) and tubular transport maximum (maximal the proximal tubule. Thus, the kidneys are not regulators
amount of the substance that can be transported by the of plasma amino acid concentrations. There are several
tubules, T max or T M ). A renal titration curve for glucose transport systems for amino acids in the proximal tubule,
is depicted in Figure 2-11.The T max for glucose is con- including systems for neutral amino acids, cationic amino
acids and cystine, anionic amino acids, imino glycine acids
stant and relatively high, so it is usually not exceeded in
(proline, hydroxyproline, glycine), and ß-amino acids
health. Consequently, the kidneys do not regulate plasma 6,52
(e.g., taurine).
glucose concentration. In humans, the T max for glucose is
approximately 375 mg/min. In the dog, it is approxi- PINOCYTOSIS
mately 100 mg/min, 27,47 and in the cat, 50 mg/min. 32
In the renal titration curve, the T max for glucose is Low-molecular-weight proteins (including several
approached somewhat gradually. This characteristic is hormones and immunoglobulin light chains) are filtered
called splay and is thought to result from nephron hetero- at the glomerulus and reabsorbed by the proximal tubular
geneity. Some nephrons excrete glucose before the aver- cells, where they are hydrolyzed to their constituent
age T max is reached, whereas others continue to reabsorb amino acids, and these are returned to the circulation. Fil-
glucose after the average T max has been reached (i.e., the tered proteins of small molecular mass may be hydrolyzed
to amino acids by brush border enzymes at the luminal
T max for glucose differs slightly among nephrons).
surface of the proximal tubular cell and their amino acids
taken into the cell by cotransport with sodium. Alterna-
800 Filtered tively, filtered proteins of larger molecular mass may
attach to endocytic sites on the luminal cell membrane.
Glucose filtered, excreted, or reabsorbed (mg/min) 600 Reabsorbed fuse with lysosomes to form endolysosomes, in which
These sites invaginate to form endosomes, which then
digestion of the proteins occurs. The amino acids leave
400
the endolysosomes and cross the basolateral membranes
Tm Gluc ≅ 375 mg/min
of the tubular cells by facilitated diffusion. This endocytic
200
Splay
exceeded in health.
Threshold mechanism has a very high capacity, which is not normally
0 UREA
0 200 400 600 800 Urea is passively reabsorbed in the proximal tubules,
Plasma glucose concentration (mg/dL) depending on tubular flow rate. Increased tubular flow,
Figure 2-11 Glucose titration curve showing filtration, as occurs during diuresis, is the result of decreased reab-
reabsorption, and urinary excretion of glucose at increasing plasma sorption of water from the tubular fluid. This decreases
glucose concentrations. Tm Gluc refers to the maximal amount of the tubular fluid urea concentration and decreases the
glucose that can be transported per minute. (Drawing by Tim Vojt.) concentration gradient of urea across the tubular