Page 108 - The Toxicology of Fishes

88 The Toxicology of Fishes

cells, as well as the urinary bladder. The kidney tubule can be subdivided further into two proximal
segments (I and II): a distal tubule and a collecting tubule. The functional kidney unit of saltwater fish
is similar to that of freshwater fish but lacks the distal tubule. In some saltwater species, the glomerulus
may also be absent.
Because they are hyperosmotic with respect to their environment, freshwater fish must eliminate large
volumes of dilute urine and retain salt (principally NaCl). High urine flow rates are supported by a high
glomerular filtration rate (GFR), which is controlled by hormones (arginine vasotocin, angiotensin, and
cortisol) that act primarily on blood pressure. Additional control of GFR may exist at the local level via
the recruitment of glomeruli. Epithelial permeabilities to water within the collecting tubule and bladder
are controlled in part by the hormone prolactin and tend to be very low. In contrast, saltwater teleosts
are hypoosmotic with respect to the environment and must overcome dehydration by drinking seawater
and absorbing water and minerals (primarily monovalent ions) through the gut. Excess salts are eliminated
across the gills (both mono- and divalent ions) and kidney (primarily divalent ions), and water loss is
minimized by producing small quantities of relatively concentrated urine. Divalent ions that are not
2+
2+
absorbed within the gut (primarily Mg and SO ) are eliminated in feces. The GFR in saltwater fish
4
is much lower than that of freshwater fish. Urine osmolarity is maintained by an exchange of divalent
and monovalent ions within the proximal tubule. Water is then reabsorbed with NaCl in the bladder.
Because it comprises up to 40% of total tubular surface, the proximal tubule of saltwater fish has been
used extensively for both in vitro and in vivo studies of kidney function (Kinter, 1966, 1975; Miller and
Pritchard, 1997; Pritchard and Miller, 1993; Pritchard and Renfro, 1984).
The mechanisms that have evolved for handling ions and water in the fish kidney also contribute to
the excretion of endogenous and exogenous organic solutes. The first step in urine formation is ultrafil-
tration of plasma through the capillary network of the glomerulus. In the lumen of the tubule, solutes
may be reabsorbed back into plasma or added to the filtrate by secretion of free chemical from the
plasma across the renal epithelium. The final composition of urine is determined by characteristics of
the epithelium in both the tubule and bladder (Miller, 1987).
Two important attributes of organic solutes that determine the effectiveness of their renal excretion
are (1) molecular size, and (2) plasma binding. Molecules with a radius of less than 20 Å are completely
filtered at the glomerulus, those with a radius between 20 and 42 Å are partially filtered, and those
with a radius greater than 42 Å are retained in plasma (Miller, 1987). Molecular size also limits renal
tubular secretion. In fish as in mammals, chemicals with molecular weights greater than 500 tend to
be secreted in the liver rather than the kidney (Pritchard and Renfro, 1984). Plasma binding is important
because glomerular filtration and tubular secretion act primarily on free or unbound chemicals in plasma.
Because they bind to plasma proteins, lipophilic compounds are generally retained by plasma as it
flows though the glomerulus. Lipophilic chemicals contained within the glomerular filtrate may be
reabsorbed from the tubule. This is particularly true of saltwater fish due to the concentrating effect of
water reabsorption.
Some of the xenobiotics that fish are exposed to exist as organic anions or cations. Other compounds
are initially taken up as neutral species and then converted to anions and cations by various biotrans-
formation pathways. In all vertebrates studied to date, including fish, anionic and cationic secretory
systems located in the proximal tubule transport charged compounds from plasma into the tubule urine
(Pritchard and Miller, 1993). The caudal vein in fish drains into the kidney, providing a substantial supply
of portal blood. Most of this portal blood bathes the kidney tubules and contributes to the renal secretory
system (Pritchard and Renfro, 1984). Overall, up to 80% of the cardiac output flows through the fish
kidney, as compared with about 20% in mammals.

Tubular Anion Secretion
The organic anion secretory system uses metabolic energy to move substrate molecules into the tubule
epithelial cells against their electrochemical gradient (Figure 3.16). This mechanism is carrier mediated,
saturable, and inhibited competitively by other substrates (Pritchard, 2001). Organic anion secretion is
+
+
a three step process: (1) ATP is hydrolyzed to drive the Na pump and create an inward Na gradient;
–2
+
(2) the Na gradient into the cell drives the uptake of α-ketoglutarate (αKG ), thereby creating an outward