PRINCIPLES OF TOXICOLOGY - Biology East Borneo

130 NEPHROTOXICITY: TOXIC RESPONSES OF THE KIDNEYFigure 6.1 The human renal excretory system: (a) the complete excretory system; (b) cross section of kidney; (c)representative section for the enlargement in Figure 6.2.actually filtered by the kidney. Of this, the kidney reabsorbs approximately 99 percent, resulting in aurine formation rate of only about 1.2 mL/min. Thus, the kidneys, which are perfused at approximately1 L/min, form urine at approximately 1 mL/min or 0.1 percent of the perfusion. Because of the highvolume of blood flow to the kidneys, a chemical in the blood is delivered to this organ in relativelylarge quantities.The kidney requires large amounts of metabolic energy to remove wastes from the blood by tubularsecretion and to return filtered nutrients back to the blood. Roughly 10 percent of the normal restingoxygen consumption is needed for the maintenance of proper kidney function. Therefore, the kidneyis sensitive to agents, such as barbiturates, that induce ischemia, a lack of oxygen caused by a decreasein blood flow. Acute intoxication by barbiturates induces severe hypotension (i.e., low blood pressure)and shock. The severe decrease in blood pressure results in a decrease in filtration of the plasma,resulting in a decrease (oliguria) or cessation (anuria) of urine formation. At an early stage this is calledpre–renal failure, and a reversal in the blood deficit to the kidney will restore normal renal function.However, a critical point is reached when renal sufficiency cannot be restored because of the cell deathcaused by ischemic anoxia, and the resultant renal failure is irreversible. In this situation, theaccumulation in the blood of wastes normally excreted (uremia) results in death. It should beremembered, then, that any agent or physical trauma that causes severe hypotension and shock mayproduce acute renal failure and eventually death by a similar mechanism.Nephrons: The Functional Units of the KidneyThe cortex of each kidney in humans contains approximately one million excretory units callednephrons. Agents toxic to the kidney generally injure these nephrons, and such agents are thereforereferred to as nephrotoxicants. Degeneration, necrosis, or injury to the nephron elements is referred toas a nephrosis or nephropathy.An individual nephron may be divided into three anatomic portions: (1) the vascular or bloodcirculatingportion, (2) the glomerulus, and (3) the tubular element (Figures 6.2 and 6.3). Theglomerulus, which is about 200 µm in diameter, is formed by the invagination of a tuft of capillaries