PRINCIPLES OF TOXICOLOGY

• Second, if blood flow is compromised long enough, tissue ischemia will result in irreversible
organ damage.
Nephrotoxicants, agents toxic to the nephron, the principal excretory unit of the kidney, also disrupt
key life-preserving functions.
• The glomerulus normally filters out the high-molecular-weight proteins from the blood.
However, toxic agents will increase its permeability, allowing these proteins to appear in
urine.
• Agents that damage the tubular element of the nephron will compromise its ability to
reabsorb solutes such as glucose and amino acids, which are necessary for normal
maintenance of the body, or disrupt sodium transport out of the nephron tubule, which
could result in diuresis or excess urine formation or an unbalancing of the body’s ionic
(salt) homeostasis.
• If damage to the nephron is excessive, renal failure can decrease or completely stop urine
flow, and cause death by poisoning from the body’s own products.
Many agents directly toxic to the nephron are commercially or industrially important.
• Mercury, lead, and cadmium are industrially the most important nephrotoxic metals.
• Halogenated hydrocarbons, particularly carbon tetrachloride and chloroform, are nephrotoxic.
• Certain therapeutic agents, such as phenacetin, aspirin, and the aminoglycoside antibiotics
are directly nephrotoxic.
Chemicals can cause nephrotoxicity indirectly:
• Some agents deposit crystals in the tubular element of the nephron, resulting in physical
damage.
• Hemolytic agents such as arsine gas are capable of pigment neuropathy by releasing
hemoglobin into the blood.
REFERENCES AND SUGGESTED READING
REFERENCES AND SUGGESTED READING 143
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Brenner, B., and F. Rector, The Kidney, Saunders, Philadelphia, 1976. Ganong, F., Review of Medical Physiology,
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Goldstein, R., and R. Schnellman, “Toxic responses of the kidney,” in Casarett and Doull’s Toxicology: The Basic
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