Block 4: Toxicology - Section 2: General Principles of Toxicology

TOX2.6: Excretion

EXCRETION:

Substances can be excreted via the lungs, stool or kidney. Most polar substances are excreted via the kidney. Substances metabolized via the liver are usually excreted in the bile and then via the stool. Fat soluble substances maybe excreted via breast milk. Excretion occurs simultaneously with distribution and biotransformation.

Kidneys:

Excretion of toxicants after biotransformation usually occurs though passive glomerular filtration or tubular diffusion. Alternatively active tubular secretion may take place. Active secretion requires energy expenditure, it is an enzyme dependent and saturable mechanism.

The kidney receives 25% of cardiac output and 20% of the output is filtered by the glomeruli. The glomeruli have pores of 70 nm which keep all the cellular components and large molecular weight proteins such as albumin in the intravascular space. Unbound toxicants with M.M. £ 60 000 daltons are filtered into the urinary space. Toxicants with high lipid/water partition coefficients are reabsorbed whereas ionized/polar substances are excreted. Bases are best excreted in acid urine and vice versa allowing one to hasten excretion by modifying the pH of the urine. Phenobarbital (a weak acid pKa = 7.2 ) is best excreted after urine alkalinization.

Liver-biliary system

Substances such as lead, arsenic, manganese, DDT, are excreted in bile. As with renal tubular excretion, plasma protein bound toxins are available for biliary excretion. Organic compounds are frequently biotransformed to polar metabolites prior to biliary excretion but intestinal microflora can hydrolyze the glucuronide or sulfate conjugates enabling reabsorption. This is termed the enterohepatic recirculation and occurs with methyl mercury and organochlorines such as DDT. Biliary excretion can be induced by phenobarbital or steroids. Adsorbents of fat or cholesterol can interrupt the enterohepatic cycle e.g. workers exposed to chlorinated hydrocarbon pesticide are treated with the bile acid resin cholestyramine.

Gut

The gut may be an route important for excretion of organometals, especially methylmercury and organochlorines such as DDT, Dioxin and PCB’s.

Lung

Postgraduate Diploma in Occupational Health (DOH) - Modules 3: Occupational Medicine & Toxicology (Basic) by Profs Mohamed Jeebhay and Rodney Ehrlich, Health Sciences UCT is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 2.5 South Africa License. Major contributors: Mohamed Jeebhay, Rodney Ehrlich, Jonny Myers, Leslie London, Sophie Kisting, Rajen Naidoo, Saloshni Naidoo. Source available from here. For any updates to the material, or more permissions beyond the scope of this license, please email healthoer@uct.ac.za or visit www.healthedu.uct.ac.za. Last updated Jan 2007.
Disclaimer note: Some resources and descriptions may be out-dated. For suggested updates and feedback, please contact healthoer@uct.ac.za.