PRINCIPLES OF TOXICOLOGY

132 NEPHROTOXICITY: TOXIC RESPONSES OF THE KIDNEY
Figure 6.3 Juxtamedullary nephron: (1) afferent arteriole; (2) efferent arteriole; (3) glomerulus; (4) proximal
convoluted tubule; (5) proximal straight tubule (pars recta); (6) descending limb of the loop of Henle; (7) thin
ascending limb of the loop of Henle; (8) thick ascending limb of the loop of Henle; (9) distal convoluted tubule;
(10) collecting duct. (Based on J. Doull, et al., eds., Casarett and Doull’s Toxicology: The Basic Science of Poisons,
2nd ed., Macmillan, New York, 1980.)
nephron consists of the proximal tubule, the loop of Henle, the distal tubule, and the collecting duct
(see Figure 6.3). The proximal tubule consists of a proximal convoluted section (pars convoluta) and
a distal straight section (pars recta). Substances that are actively reabsorbed in the proximal tubule
include glucose, sodium, potassium, phosphate, amino acids, sulfate, and uric acid. Essentially all
amino acids and glucose are reabsorbed in the proximal tubule, and virtually none normally appear in
the urine. Agents toxic to the proximal tubule cause amino acids and glucose to appear in the urine
(aminoaciduria and glycosuria). Even though 250 g of glucose normally passes through the kidney
daily, no more than 100 mg is usually excreted in 24 h. However, glucose does appear in excess
quantities in the urine if high blood glucose levels produce a glucose load in the filtrate and this exceeds
the resorptive capacity of the proximal tubule of the nephrons. This occurs in diabetes mellitus, in
which excess glucose appears in urine because excessive amounts of glucose in the blood plasma
filtrate have overwhelmed the glucose transport system in the nephron. Water is also reabsorbed in the
proximal tubule because of an osmotic gradient between the filtrate in the tubule and the blood plasma.
Thus, isotonicity is maintained in the proximal tubule even though there is a selective reabsorption of
solutes. Approximately 75 percent of the glomerular filtrate fluid is reabsorbed in the proximal tubule.