Excretion and Elimination of Toxicants and their M Essay

Published: 2021-06-29 01:46:35
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etabolitesExcretion and Elimination of Toxicants and their Metabolites The first topic that was covered by this chapter was the excretion of wastesby the Renal system. The first step that occurs in the kidney deals with thenephron, which is the functional unit of the kidney. In the glomerulus theformation of urine begins with the passive filtration of plasma through thepores that are found in the glomerulus. The plasma is forced through these poresby hydrostatic pressure. The only things that determines if a molecule will passthrough the pores of the glomerulus is it’s molecular weight. The lower themolecular weight, the easier it will pass through the pores.
Anotherdetermining factor will be if a molecule is bound to a large molecule. If thisis true then passage through the pores will be hindered by the size of thelarger molecule. Reabsorbtion of the many ions, minerals and other nutrients that escaped inthe glomerular filtrate will need to be recovered. . Reabsorbtion begins in thetubules of the nephron.
Anywhere from 65% to 90% of reabsorbtion occurs inthese structures. Active reabsortion is used to recapture glucose, proteins,amino acids and other nutrients. Water and chloride ions are passivelyreabsorbed by the establishment of osmotic and electrochemical gradients. Boththe Loop of Henley and collecting duct are used to establish these osmolargradients. The tubule has a brush border that will absorb proteins andpolypeptides through pinocytosis.
These molecules are sometimes catabolised andconverted into amino acids. and returned to the blood. Sometimes theaccumulation of these proteins can lead to renal toxicity A second process that occurs in the tubules is tubular secretion. This isanother mechanism used to excrete solutes. Secretion may be either passive oractive. Secretions include organic bases, which occur in the pars recta of theproximal tubule.
Secretions of weak bases and two weak acids occur passively. Other mechanisms involves the use of a mechanism that is called ion trapping. Ata certain pH the compounds are more ionized. Outside of the tubule thesecompounds are non-ionized and are lipophilic. Thus they are able to diffuseacross the membranes of the tubule.
Once inside, the pH of the tubule willionize them and render then unable to pass across the cell membranes. The removal of xenobiotics is dependant on many factors. First is thepolarity of the xenobiotic. Polar compounds are soluble in the plasma water aremore easily removed by the kidneys through the use of glomerular filtration. Thefaster the rate of glomerular filtration , the faster the polar xenobiotics areeliminated from the body. Other factors that affect the rate of eliminationinclude: dose of the xenobiotic, the rate pf absorbtion, and the ability to bindto proteins as well as the polarity of the compound.
In comparison lipophilic compounds will cross the cell membrane with moreease. Due to their lipohpillic properties they will follow the theirconcentration gradient across the membrane of the tubules and are ,therefore,easily retained by the body. If a lipophilic compound is metabolized to a morepolar state then it is more easily metabolized. Another important factor thatwill determine excretion by the kidneys will be the pH of the environment. Thosecompounds 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 theirbecause of their change to an ionized form. The liver is the second most important organ that is involved in the removalof wastes from the body. The primary methood of excretion involvrd the Hepaticcells of the liver. Both passive and active modes of transport are used.
Bile is excreted by the hepatic cells. It is a concentration of amphipaticcompounds 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 storedand concentrated in the gall bladder. The bile will then be reabsorbed by aprocess known as enterohepatic circulation. The more lipophilic or nonionized a compound is, the more readily it will beabsorbed.
Solubility is another factor that will determine absorbance. The rapidabsorbance of these compounds does not mean that they will not be readilyexcreted. Some compounds are readily excreted after absorbtion. Most toxic xenobiotics are very lipophilic. This means that they will beeasily ablorbed and dispursed among the tissue.
Their liphilic characterizationsalso means that there excretion in either the urine or bile will be in verysmall amounts, unless they are metabolized ito more polar compounds. One of the methods used to dispose toxic lipophilics is by degradation of thelarge compounds into small polar fragments thatcan be eliminated through theurine or bile. Oxidative metabolism of toxic cyclic and polycyclic hydrocarbonsis done with the introduction of a hyroxyl group into the ring structure. Theexcretion of halogenated hydrocarbons is extremely difficult. Their accumulationin the body occurs in both adipose tissue and lipid layers of the skin.
Theywill stay there for the duration of theanimals life time. The molecular weight of a compound will determine if the compound will beexcreted in the urine or feces. Any elimination of a xenobiotic will be done inassociation with the excretion of another compound that is normally eliminatedby the body. Most gaseous and volatile xenobiotics are eliminated through thelungs. 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 willinvolve the use of the mucociliary bronchotracheal escalator that will end withthe material being swallowed and passed out of th body. Sex linked elimination is restricted to the female. The milk excreted by themother will contain the largest number of possible xenobiotics. The eliminationof the xenobiotic is dependant on the half-lifeof the compound.
Most of thecompounds 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 thatare excreted are lipophilic because they are not excreted by the other majorpathways. In eggs the type of compound eliminated are also limpohpilic innature.
Fetuses are mostly effected by lipophilic compounds that are ablr topass the placental barrier. There are cases of fatal exposure of xenobiotics tothe fetus through the mother. Science

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