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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.


The functional integrity of the mammalian kidney is vital to total body homeostasis, because of its role in the excretion of metabolic wastes, synthesis and release of the hormones renin and erythropoietin, and the regulation of extracellular fluid volume, electrolyte composition, and acid–base balance.


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 receives about 90 percent of blood flow compared with the medulla (˜6 to 10 percent) or papilla (1 to 2 percent). Thus, when a blood-born 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. The functional unit of the kidney, the nephron, may be considered in three portions: the vascular element, the glomerulus, and the tubular element.

Figure 14–1
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Schematic of the human kidney showing the major blood vessels and the microcirculation and tubular components of each nephron. (From Guyton AC, Hall JE (11th ed.): Textbook of Medical Physiology. Philadelphia: Saunders, 2006, p. 318, with permission from Elsevier.)


Renal Vasculature and Glomerulus


The renal artery branches into 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 nerve stimulation, angiotensin II, vasopressin, endothelin, adenosine, and norepinephrine. The efferent arterioles draining the cortical glomeruli branch into a peritubular capillary network, whereas those draining the juxtamedullary glomeruli form a capillary loop, the vasa recta, supplying the medullary structures. These postglomerular capillary loops provide the delivery of nutrients to the postglomerular tubular structures, delivery of wastes to the tubule for excretion, and return of reabsorbed electrolytes, nutrients, and water to the systemic circulation.


The glomerulus is a complex, specialized capillary bed that filters a portion of the blood into an ultrafiltrate that passes into the tubular portion of the nephron. The formation of such an ultrafiltrate is the net result of ...

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