PRINCIPLES OF TOXICOLOGY - Biology East Borneo

6 Nephrotoxicity: Toxic Responses of theKidneyNEPHROTOXICITY: TOXIC RESPONSES OF THE KIDNEYPAUL J. MIDDENDORF and PHILLIP L. WILLIAMSThis chapter will give the environmental and occupational health professional information about• The importance of kidney functions• How toxic agents disrupt kidney functions• Measurements performed to determine kidney dysfunctions• Occupational and environmental agents that cause kidney toxicity6.1 BASIC KIDNEY STRUCTURES AND FUNCTIONSThe principal excretory organs in all vertebrates are the two kidneys. The primary function of thekidney in humans is removing wastes from the blood and excreting the wastes in the form of urine.However, the kidney plays a key role in regulating total body homeostasis. These homeostatic functionsinclude the regulation of extracellular volume, the regulation of calcium metabolism, the control ofelectrolyte balance, and the control of acid–base balance.The adult kidneys of reptiles, birds, and mammals (including humans) are nonsegmental and drainwastes only from the blood (principally breakdown products of protein metabolism). The kidneys arepaired organs that lie behind the peritoneum on each side of the spinal column in the posterior aspectof the abdomen. The adult human kidney is approximately 11 cm long, 6 cm broad, and 2.5 cm thick.In human adults individual kidneys weigh 125–170 g for males and 115–155 g for females. The renalartery and vein pass through the hilus, which is a slit in the medial or concave surface of each kidney(Figure 6.1b). From each kidney a common collecting duct, the ureter, carries the urine posteriorly tothe bladder where it can be voided from the body.Each human kidney consists of an outer cortex and an inner medulla (see Figures 6.1b and 6.2).The cortex constitutes the major portion of the kidney and receives about 85 percent of the total renalblood flow. Consequently, if a toxicant is delivered to the kidney in the blood, the cortex will be exposedto a very high proportion.Blood Flow to the KidneysThe kidneys represent approximately 0.5 percent of the total body weight, or approximately 300 g ina 70-kg human. Yet the kidneys receive just under 25 percent of the total cardiac output, which is about1.2–1.3 L blood/min, or 400 mL/100 g tissue/min. The rate of blood flow through the kidneys is muchgreater than through other very well perfused tissues, including brain, heart, and liver. If the normalblood hematocrit (i.e., that proportion of blood that is red blood cells) is 0.45, then the normal renalplasma flow is approximately 660 to 715 mL/min. Yet only 125 mL/min of the total plasma flow isPrinciples of Toxicology: Environmental and Industrial Applications, Second Edition, Edited by Phillip L. Williams,Robert C. James, and Stephen M. Roberts.ISBN 0-471-29321-0 © 2000 John Wiley & Sons, Inc.129