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INTRODUCTION

KEY POINTS

  • 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.

  • Vitamin D3 is metabolized to the active 1,25-dihydroxy vitamin D3 form.

FUNCTIONAL ANATOMY

A sagittal section of the kidney reveals three clearly demarcated anatomic areas: the cortex, medulla, and papilla (Fig. 14–1). The cortex receives a disproportionately higher percentage (90%) of blood flow compared to the medulla (about 6% to 10%) or papilla (1% to 2%). 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. (Reprinted from Guyton AC, Hall JE, eds. Textbook of Medical Physiology. Philadelphia, PA: WB Saunders; 1996: p. 318.)

Renal Vasculature and Glomerulus

The renal artery branches successively into the afferent arterioles (Fig. 14–1), which supply the glomerulus. Blood leaves the glomerular capillaries via the efferent arteriole. 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 contract in response to nerve stimulation, angiotensin II, vasopressin, endothelin, adenosine, and norepinephrine decreasing glomerular filtration rate and renal blood flow. 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 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 fractionates blood into a virtually protein-free and cell-free ultrafiltrate, which passes through Bowman’s space and into the tubular portion of the nephron. The formation of such an ultrafiltrate ...

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