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KEY POINTS

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  • The kidney contributes to total body homeostasis via its role in the excretion of metabolic wastes, the synthesis and release of renin and erythropoietin, and the regulation of extracellular fluid volume, electrolyte composition, and acid–base balance.

  • Xenobiotics in the systemic circulation will be delivered to the kidney in relatively high amounts.

  • The processes that concentrate urine also serve to concentrate potential toxicants in the tubular fluid.

  • Renal transport, accumulation, and biotransformation of xenobiotics contribute to the susceptibility of the kidney to toxic injury.

  • Numerous nephrotoxicants cause mitochondrial dysfunction via compromised respiration and ATP production, or some other cellular process, leading to either apoptosis or necrosis.

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INTRODUCTION

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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-dihydroxyvitamin 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.

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FUNCTIONAL ANATOMY

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Gross examination of a sagittal section of the kidney reveals three clearly demarcated anatomical areas: the cortex, medulla, and papilla (Figure 14–1). The cortex constitutes the major portion of the kidney and receives a disproportionately higher percentage (90%) of blood flow compared with the medulla (∼6% to 10%) or papilla (1% to 2%). Thus, when a bloodborne 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.

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FIGURE 14–1

Schematic of the human kidney showing the major blood vessels and the microcirculation and tubular components of each nephron. (Reproduced with permission from Guyton AC, Hall JE: Textbook of Medical Physiology. 9th edition. Philadelphia, PA: Saunders/Elsevier; 1996.)

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The functional unit of the kidney, the nephron, may be considered in three portions: the vascular element, the glomerulus, and the tubular element.

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Renal Vasculature and Glomerulus

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The renal artery branches successively into interlobar, arcuate, interlobular arteries and afferent arterioles that supply the glomerulus (Figure 14–1). Blood then leaves the glomerular capillaries via the efferent arterioles. Both the afferent and efferent arterioles control glomerular capillary pressure and glomerular plasma flow rate. These arterioles are innervated by the sympathetic nervous system and respond to ...

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