Ganong's Review of Medical Physiology, 23rd Edition

648 SECTION VIII Renal Physiology

equals the amount filtered plus the net amount transferred by
the tubules. This latter quantity is conveniently indicated by
the symbol TX (Figure 38–7). The clearance of the substance
equals the GFR if there is no net tubular secretion or reabsorp-
tion, exceeds the GFR if there is net tubular secretion, and is
less than the GFR if there is net tubular reabsorption.
Much of our knowledge about glomerular filtration and
tubular function has been obtained by using micropuncture
techniques. Micropipettes can be inserted into the tubules of
the living kidney and the composition of aspirated tubular
fluid determined by the use of microchemical techniques. In
addition, two pipettes can be inserted in a tubule and the
tubule perfused in vivo. Alternatively, isolated perfused seg-
ments of tubules can be studied in vitro, and tubular cells can
be grown and studied in culture.

MECHANISMS OF TUBULAR

REABSORPTION & SECRETION

Small proteins and some peptide hormones are reabsorbed in
the proximal tubules by endocytosis. Other substances are se-
creted or reabsorbed in the tubules by passive diffusion between
cells and through cells by facilitated diffusion down chemical or
electrical gradients or active transport against such gradients.
Movement is by way of ion channels, exchangers, cotransport-
ers, and pumps. Many of these have now been cloned, and their
regulation is being studied.
It is important to note that the pumps and other units in the
luminal membrane are different from those in the basolateral
membrane. It is this different distribution that makes possible
net movement of solutes across the epithelia.
Like transport systems elsewhere, renal active transport sys-
tems have a maximal rate, or transport maximum (Tm), at

which they can transport a particular solute. Thus, the amount

of a particular solute transported is proportional to the amount

present up to the Tm for the solute, but at higher concentrations,

the transport mechanism is saturated and there is no apprecia-

ble increment in the amount transported. However, the Tms for

some systems are high, and it is difficult to saturate them.

It should also be noted that the tubular epithelium, like that

of the small intestine, is a leaky epithelium in that the tight

junctions between cells permit the passage of some water and

electrolytes. The degree to which leakage by this paracellular

pathway contributes to the net flux of fluid and solute into and

out of the tubules is controversial since it is difficult to measure,

but current evidence seems to suggest that it is a significant fac-

tor in the proximal tubule. One indication of this is that para-

cellin-1, a protein localized to tight junctions, is related to Mg2+

reabsorption, and a loss-of-function mutation of its gene causes

severe Mg2+ and Ca2+ loss in the urine.

The effects of tubular reabsorption and secretion on sub-

stances of major physiologic interest are summarized in Table

38–5.

Na+ REABSORPTION

The reabsorption of Na+ and Cl– plays a major role in body

electrolyte and water homeostasis. In addition, Na+ transport

is coupled to the movement of H+, glucose, amino acids, or-

ganic acids, phosphate, and other electrolytes and substances

across the tubule walls. The principal cotransporters and ex-

changers in the various parts of the nephron are listed in Table

38–6. In the proximal tubules, the thick portion of the ascend-

ing limb of the loop of Henle, the distal tubules, and the col-

lecting ducts, Na+ moves by cotransport or exchange from the

tubular lumen into the tubular epithelial cells down its con-

centration and electrical gradients, and is then actively

pumped from these cells into the interstitial space. Na+ is

pumped into the interstitium by Na, K ATPase in the basolat-

eral membrane. Thus, Na+ is actively transported out of all

parts of the renal tubule except the thin portions of the loop of

Henle. The operation of the ubiquitous Na+ pump is consid-

ered in detail in Chapter 2. It extrudes three Na+ in exchange

for two K+ that are pumped into the cell.

The tubular cells along the nephron are connected by tight

junctions at their luminal edges, but there is space between

the cells along the rest of their lateral borders. Much of the

Na+ is actively transported into these extensions of the inter-

stitial space, the lateral intercellular spaces (Figure 38–8).

Normally about 60% of the filtered Na+ is reabsorbed in the

proximal tubule, primarily by Na–H exchange. Another 30%

is absorbed via the Na–2Cl–K cotransporter in the thick

ascending limb of the loop of Henle, and about 7% is

absorbed by Na–Cl cotransporter in the distal convoluted

tubule. The remainder of the filtered Na+, about 3%, is

absorbed via the ENaC channels in the collecting ducts, and

this is the portion that is regulated by aldosterone in the pro-

duction of homeostatic adjustments in Na+ balance.

FIGURE 38–7 Tubular function. For explanation of symbols,
see text.

GFR x PX + TX = UXV ̇

̇

Filtered

= GFR x PX

Re-

absorbed

Excreted

= UXV

Secreted

TX = Positive

GFR x PX < UXV

Example: PAH

̇

TX = Negative

GFR x PX > UXV

Example: Glucose

̇

̇

TX = 0

GFR x PX = UXV

Example: Inulin