Page 173 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

tion curve reaches plateau, and slope of PAH
Excretion of Organic Substances
excretion curve decreases). Some organic an-
Food provides necessary nutrients, but also ions (e.g., urate and oxalate) and cations (e.g.,
contains inert and harmful substances. The choline) are both secreted and reabsorbed (bi-
body can usually sort out these substances al- directional transport), which results in net re-
ready at the time of intake, either based on absorption (urate, choline) or net secretion
their smell or taste or, if already eaten, with the (oxalate).
–
help of specific digestive enzymes and intesti- The secreted organic anions (OA ) include
nal absorptive mechanisms (e.g., D-glucose indicators such as PAH (p-aminohippurate;
Kidneys, Salt, and Water Balance stools): useful bile salts are almost completely numerous diuretics (! p. 172); and conjugated
! p. 150) and phenol red; endogenous sub-
and L-amino acids are absorbed, but L-glucose
and D-amino acids are not). Similar distinc-
stances such as oxalate, urate, hippurate;
drugs such as penicillin G, barbiturates, and
tions are made in hepatic excretion (! bile !
above)
(see
containing
reabsorbed from the gut by way of specific car-
glu-
substances
curonate, sulfate or glutathione. Because of its
riers, while waste products such as bilirubin
high affinity for the transport system, pro-
are mainly eliminated in the feces. Likewise,
–
the kidney reabsorbs hardly any useless or
benecid is a potent inhibitor of OA secretion.
harmful substances (including end-products
The active step of OA secretion (! B) occurs across
–
such as creatinine). Valuable substances (e.g.,
and accumulates organic anions in the cell whereby
hand, are reabsorbed via specific transporters
the inside-negative membrane potential has to be
and thus spared from excretion (! p. 158).
overcome. The membrane has a broad specificity
7 D-glucose and L-amino acids), on the other the basolateral membrane of proximal tubule cells
carrier (OAT1 = organic anion transporter type 1) that
The liver and kidney are also able to modify
–
endogenous waste products and foreign com- transports OA from the blood into the tubule cells 2–
pounds (xenobiotics) so that they are ”detox- in exchange for a dicarboxylate, such as succinate
2 –
ified” if toxic and made ready for rapid elimi- or α-ketoglutarate ; ! B1). The latter substance
arises from the glutamine metabolism of the cell
nation. In unchanged form or after the enzy- (! p. 177 D2); the human Na -dicarboxylate trans-
+
matic addition of an OH or COOH group, the porter hNADC-1 also conveys dicarboxylates (in com-
substances then combine with glucuronic bination with 3 Na ) into the cell by secondary active
+
–
acid, sulfate, acetate or glutathione to form transport (! B2). The transport of OA is therefore
–
conjugates. The conjugated substances are called tertiary active transport. The efflux of OA into
then secreted into the bile and proximal tubule the lumen is passive (facilitated diffusion; ! B3). An
lumen (with or without further metabolic ATP-dependent conjugate pump (MRP2 = multi-drug
resistance protein type 2) in the luminal membrane
processing). is also used for secretion of amphiphilic conjugates,
such as glutathione-linked lipophilic toxins (! B4).
Tubular Secretion
+
The proximal tubule utilizes active transport The organic cations (OC ) secreted include en-
mechanisms to secrete numerous waste prod- dogenous substances (epinephrine, choline,
ucts and xenobiotics. This is done by way of histamine, serotonin, etc.) and drugs (atropine,
–
carriers for organic anions (OA ) and organic quinidine, morphine, etc.). +
+
cations (OC ). The secretion of these sub- The active step of OC secretion occurs
stances makes it possible to raise their clear- across the luminal membrane of proximal
ance level above that of inulin and, therefore, tubule cells (luminal accumulation occurs
to raise their fraction excretion (FE) above 1.0 = after overcoming the negative membrane
100% (! p. 152) in order to eliminate them potential inside the cell). The membrane con-
more effectively (! A; compare red and blue tains (a) direct ATP-driven carriers for organic
+
curves). Secretion is carrier-mediated and is cations (mdr1; primary active OC transport;
+
+
therefore subject to saturation kinetics. Unlike ! C1) and (b) a multispecific OC /H antiporter
+
reabsorbed substances such as D-glucose (tertiary active transport; ! C2). The OC dif-
(! p. 159 A), the fractional excretion (FE) of or- fuse passively from the blood into the cell by
160 ganic anions and cations decreases when their way of a polyspecific organic cation trans-
plasma concentrations rise (! A; PAH secre- porter (OCT; ! C3).
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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