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  • Functional Anatomy

    • Renal Vasculature and Glomerulus

    • Proximal Tubule

    • Loop of Henle

    • Distal Tubule and Collecting Duct

  • Pathophysiologic Responses of the Kidney

    • Acute Kidney Injury

    • Adaptation Following Toxic Insult

    • Chronic Kidney Disease

  • Susceptibility of the Kidney to Toxic Injury

    • Incidence and Severity of Toxic Nephropathy

    • Reasons for the Susceptibility of the Kidney to Toxicity

    • Site-Selective Injury

    • Glomerular Injury

    • Proximal Tubular Injury

    • Loop of Henle/Distal Tubule/Collecting Duct Injury

    • Papillary Injury

  • Assessment of Renal Function

  • Biochemical Mechanisms/Mediators of Renal Cell Injury

    • Cell Death

    • Mediators of Toxicity

    • Cellular/Subcellular and Molecular Targets

  • Specific Nephrotoxicants

    • Heavy Metals

      • Mercury

      • Cadmium

    • Chemically Induced α2u-Globulin Nephropathy

    • Halogenated Hydrocarbons

      • Chloroform

      • Tetrafluoroethylene

    • Aristolochic Acid and Fungal Toxins

    • Therapeutic Agents

      • Acetaminophen

      • Nonsteroidal Anti-Inflammatory Drugs

      • Aminoglycosides

      • Amphotericin B

      • Cyclosporine

      • Cisplatin

      • Radiocontrast Agents

The functional integrity of the mammalian kidney is vital to total body homeostasis because the kidney plays a principal role in the excretion of metabolic wastes and in the regulation of extracellular fluid volume, electrolyte composition, and acid–base balance. In addition, the kidney synthesizes and releases hormones, such as renin and erythropoietin, and metabolizes vitamin D3 to the active 1,25-dihydroxy vitamin D3 form. A toxic insult to the kidney therefore could disrupt any or all of these functions and could have profound effects on total body metabolism. Fortunately, the kidneys are equipped with a variety of detoxification mechanisms and have considerable functional reserve and regenerative capacities. Nonetheless, the nature and severity of the toxic insult may be such that these detoxification and compensatory mechanisms are overwhelmed, and kidney injury ensues. The outcome of renal failure can be profound; permanent renal damage may result, requiring chronic dialysis treatment or kidney transplantation.

Functional Anatomy

Gross examination of a sagittal section of the kidney reveals three clearly demarcated anatomic areas: the cortex, medulla, and papilla (Figs. 14-1 and 14-2). The cortex constitutes the major portion of the kidney and receives a disproportionately higher percentage (90%) of blood flow compared to the medulla (~6%–10%) or papilla (1%–2%). Thus, when a blood-borne toxicant is delivered to the kidney, a high percentage of the material will be delivered to the cortex and will have a greater opportunity to influence cortical rather than medullary or papillary functions. However, medullary and papillary tissues are exposed to higher luminal concentrations of toxicants for prolonged periods of time, a consequence of the more concentrated tubular fluid and the more sluggish flow of blood and filtrate in these regions.

Figure 14-1.

Schematic of the human kidney showing the major blood vessels and the microcirculation and tubular components of each nephron. (From Guyton AC, Hall JE, eds. Textbook of Medical Physiology. Philadelphia: WB Saunders; 1996:318, with permission from Elsevier.)

Figure 14-2.

Schematic of short- and long-looped nephrons and the collecting system. A medullary ray is delineated by a dashed line within the cortex. (1) Renal corpuscle including Bowman’s capsule and ...

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