Excretion And Elimination Of Toxicants And Their Metabolites Essay, Research Paper

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.

Reabsorbtion of the many ions, minerals and other nutrients that escaped in

the glomerular filtrate will need to be recovered.. Reabsorbtion begins in the

tubules of the nephron. Anywhere from 65% to 90% of reabsorbtion 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 dependant 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 absorbtion, 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 common bile duct, it will be stored

and concentrated in the gall bladder. The bile will then be reabsorbed by a

process known as enterohepatic circulation.

The more lipophilic or nonionized a compound is, the more readily it will be

absorbed. Solubility is another factor that will determine absorbance. The rapid

absorbance of these compounds does not mean that they will not be readily

excreted. Some compounds are readily excreted after absorbtion.

Most toxic xenobiotics are very lipophilic. This means that they will be

easily ablorbed and dispursed among the tissue. Their liphilic characterizations

also means that there excretion in either the urine or bile will be in very

small amounts, unless they are metabolized ito more polar compounds.

One of the methods used to dispose toxic lipophilics is by degradation of the

large compounds into small polar fragments thatcan be eliminated through the

urine or bile. Oxidative metabolism of toxic cyclic and polycyclic hydrocarbons

is done with the introduction of a hyroxyl group into the ring structure. The

excretion of halogenated hydrocarbons is extremely difficult. Their accumulation

in the body occurs in both adipose tissue and lipid layers of the skin. They

will stay there for the duration of theanimals life time.

The molecular weight of a compound will determine if the compound will be

excreted in the urine or feces. Any elimination of a xenobiotic will be done in

association with the excretion of another compound that is normally eliminated

by the body. Most gaseous and volatile xenobiotics are eliminated through the

lungs. The rate of ecretion is based on how soluble the compond is in the blood,

the rate of volume of respiration, and the rateof blood flow to the lungs.

Asecond method used is the alveolobronchilar transport mechanism. Which will

involve the use of the mucociliary bronchotracheal escalator that will end with

the material being swallowed and passed out of th body.

Sex linked elimination is restricted to the female.The milk excreted by the

mother will contain the largest number of possible xenobiotics.The elimination

of the xenobiotic is dependant on the half-lifeof the compound. Most of the

compounds that are excreted are low in dosage and therefore are not lethal.

Chronic exposure can be toxic to the nursing young. The type of materials that

are excreted are lipophilic because they are not excreted by the other major

pathways. In eggs the type of compound eliminated are also limpohpilic in

nature. Fetuses are mostly effected by lipophilic compounds that are ablr to

pass the placental barrier. There are cases of fatal exposure of xenobiotics to

the fetus through the mother.