Page 45 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

34 APPLIED PHYSIOLOGY

the available surface area and 90% to 95% of water trans- the lipid bilayer of the cell membrane, which occurs for
port. Both passive and active transport processes occur by substances with high lipid solubility. Simple diffusion
the transcellular route, and all active transport processes can also occur through hydrophilic protein channels
must occur by this route. embedded in the cell membrane. Simple diffusion
That renal tubular reabsorption occurs may be requires no expenditure of metabolic energy. The rate
recognized intuitively by considering the composition of transfer of solute is dependent on the permeability
of normal urine. Many low-molecular-weight solutes characteristics of the membrane, the electrochemical gra-
essential to normal physiologic function (e.g., glucose, dient (i.e., the combination of the electrical PD and
amino acids, bicarbonate) are freely filtered at the glomer- chemical concentration difference across the membrane),
ulus but do not normally appear in urine. Thus, they must and the hydrostatic pressure across the membrane. The
have been reabsorbed along the course of the renal rate of diffusion is linearly related to the concentration
tubule. In the proximal tubule, water follows solute reab- of the diffusing solute, and there is no maximal rate of
sorption osmotically, and solute reabsorption is said to transfer (V max ). Passive diffusion is not a saturable process
occur isosmotically (i.e., the reabsorbed fluid has the because a carrier is not involved.
same osmolality as extracellular fluid). Approximately Facilitated diffusion is the movement of a substance
two thirds of all water and solute reabsorption occurs across a membrane down its electrochemical gradient
in the proximal tubules. Almost 99% of glucose and after binding with a specific carrier protein in the mem-
amino acids and 90% or more of bicarbonate are brane. The carrier protein binds the substance to be
reabsorbed in the early proximal tubules (Fig. 2-9). transported at one side of the cell membrane. The
The reabsorption of bicarbonate occurs as a consequence occupied carrier then undergoes a conformational change
of the tubular secretion of hydrogen ions and is crucial to that causes translocation of the substance across the cell
renal regulation of acid-base balance (see Chapter 9). membrane. The substance is then released from the car-
rier on the other side of the membrane. Unlike simple dif-
RENAL TRANSPORT PROCESSES fusion, facilitated diffusion is a saturable process
Four types of transport processes contribute to renal characterized by a maximal rate of transfer (V max ) because
tubular reabsorption: passive diffusion, facilitated diffu- a carrier is involved. The carrier has structural specificity
sion, primary active transport, and secondary active and affinity for the substance transported, and the process
transport. is subject to competitive inhibition. Facilitated diffusion
Passive diffusion is the movement of a substance does not directly require metabolic energy, and transfer
across a membrane as a result of random molecular may occur in either direction across the membrane,
motion. Simple diffusion can take place directly through depending on the prevailing electrochemical gradient.
Examples of facilitated diffusion in the proximal tubule
include the transport of glucose and amino acids at the
basolateral membrane.
1.4
Primary active transport is the movement of a sub-
stance across a membrane in combination with a carrier
Ratio of tubular fluid concentration to plasma fluid concentration 1.0 Phosphate transport requires metabolic energy, which is supplied
Chloride
1.2
protein but against an electrochemical gradient. Active
Sodium, osmolality
by the hydrolysis of adenosine triphosphate (ATP). It is
0.8
a saturable process characterized by a V max and is subject
to metabolic (e.g., cellular oxidative poisons) and com-
0.6
petitive (e.g., competition for the carrier by a structurally
similar compound) inhibition. Examples of primary
0.4
þ
þ
(Na ,
phosphatase
K -ATPase)
basolateral
in
þ
Bicarbonate
0.2
membranes of tubular cells throughout the nephron,
Amino acids, glucose active transporters þ include Na , K -adenosinetri-
þ
0 H -ATPase in luminal membranes of tubular cells
0 100 þ þ
throughout the nephron, and H ,K -ATPase in luminal
Percentage of proximal tubular length
membranes of a-intercalated cells in the collecting ducts.
Secondary active transport is the movement of two
Lumen positive substances across a membrane after combination with a
0
Lumen negative single carrier protein. The process is called cotransport
Transepithelial potential difference if the transported substances are moving in the same
Figure 2-9 Changes in the solute composition and transepithelial direction across the membrane (e.g., glucose, amino
potential difference along the length of the proximal acids, or phosphate with sodium at the luminal mem-
nephron. (Drawing by Tim Vojt.) brane of the proximal tubular cell) and countertransport