Excretion and Elimination of Toxicants and Their Metabolites

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Excretion and Elimination of Toxicants and their Metabolites

The first topic that was covered by this chapter was the excretion of wastes by the Renal system. The first step that occurs in the kidney deals with the nephron, which is the functional unit of the kidney. In the glomerulus the formation of urine begins with the passive filtration of plasma through the pores that are found in the glomerulus. The plasma is forced through these pores by hydrostatic pressure. The only things that determines if a molecule will pass through the pores of the glomerulus is it's molecular weight. The lower the molecular weight, the easier it will pass through the pores. Another determining factor will be if a molecule is bound to a large molecule. If this is true then passage through the pores will be hindered by the size of the larger molecule.

Reabsorption
of the many ions, minerals and other nutrients that escaped in the glomerular filtrate will need to be recovered.. Reabsorption begins in the
tubules of the nephron. Anywhere from 65% to 90% of reabsorption occurs in
these structures. Active reabsortion is used to recapture glucose, proteins, amino acids and other nutrients. Water and chloride ions are passively reabsorbed by the establishment of osmotic and electrochemical gradients. Both the Loop of Henley and collecting duct are used to establish these osmolar gradients. The tubule has a brush border that will absorb proteins and polypeptides through pinocytosis. These molecules are sometimes catabolised and converted into amino acids. and returned to the blood. Sometimes the accumulation of these proteins can lead to renal toxicity

A second process that occurs in the tubules is tubular secretion. This is another mechanism used to excrete solutes. Secretion may be either passive or active. Secretions include organic bases, which occur in the pars recta of the proximal tubule. Secretions of weak bases and two weak acids occur passively. Other mechanisms involves the use of a mechanism that is called ion trapping. At a certain pH the compounds are more ionized. Outside of the tubule these compounds are non-ionized and are lipophilic. Thus they are able to diffuse across the membranes of the tubule. Once inside, the pH of the tubule will ionize them and render then unable to pass across the cell membranes. The removal of xenobiotics is dependent

on many factors. First is the
polarity of the xenobiotic. Polar compounds are soluble in the plasma water are more easily removed by the kidneys through the use of glomerular filtration. The faster the rate of glomerular filtration , the faster the polar xenobiotics are eliminated from the body. Other factors that affect the rate of elimination include: dose of the xenobiotic, the rate pf absorption

, and the ability to bind
to proteins as well as the polarity of the compound.
In comparison lipophilic compounds will cross the cell membrane with more ease. Due to their lipohpillic properties they will follow the their concentration gradient across the membrane of the tubules and are ,therefore, easily retained by the body. If a lipophilic compound is metabolized to a more polar state then it is more easily metabolized. Another important factor that will determine excretion by the kidneys will be the pH of the environment. Those compounds that are effected by pH will have both an ionized and nonionic form. When in their nonionized form it will rebsorbed by the tubules and kept their because of their change to an ionized form.

The liver is the second most important organ that is involved in the removal of wastes from the body. The primary methood of excretion involvrd the Hepatic cells of the liver. Both passive and active modes of transport are used. Bile is excreted by the hepatic cells. It is a concentration of amphipatic compounds that will aid in the transport of lipids from the small intestine. Before reaching the small intestine, via the...
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