Principles Lec 4 2013

Bone eg pb2 incorporated in matrix instead of calcium

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Unformatted text preview: of calcium Ca2+ - Like fluorine (F-), similar charge and size, mistaken identity (OH-) cause fluorosis with skeletal weakening - Hydroxyapatite (normal bone crystal), not permanent, regular bone turnover (osteoclasts) 3. Teeth (e.g. antibiotics)- cause discoloration - Fluoride as well, replaces natural (OH- )in tooth enamel crystals Storage of Chemicals in Body get a lot of xenobiotics both organs have a lot of xenobiotics transporters get bound to proteins and stay there 4. Liver and kidney (e.g. Fe2+ / Cu2+) - proteins (metallothionein) bind and sequester toxins in these compartments - many transporters can facilitate access for wide range of toxicants - concentration in liver can be 50 X higher than blood after 30 mins 5. Lung (e.g. Paraquat) Specific one-way transport mechanism Energy dependant Storage of Chemicals in Body Effect on Toxicity: if a compound gets stored, it increases residency time and increases acute affects 1. acute toxicity - Cannot reach site of action! - Also will alter dosages with pharmaceuticals 2. chronic toxicity because of chemical residues because of increased residency time - Still present in the body, not metabolized or changed! - Will be released when fat stores are mobilized for energy (acid flashbacks) because things are not circulating 3. Decreased elimination - Bound molecules too big for filtration - Sequestered in Organs outside of blood stream - Important for detection, drug testing (Steroids/ THC) Paraquat Toxicity Case Study #4 Paraquat Characteristics: Common industrial herbicide i) used at low dose - safe ii) Can be ingested and inhaled = toxicity used as a spray, because of dermal absorption oral absorption is poor can’t make its way through your skin easily toxic if it gets into your blood Toxicity: absorbed by specific protein in blood, and can accumulate in different tissues like the lungs LD50 oral 25-100 mg/kg *** dermal >200 mg/kg (poor ability to cross epidermis) Inhalation very low Used as “spray” Absorbed by specific organic cation transporter (OCT) accumulates in lung, kidney and liver Pathology Pathogenesis: 1.) Acute phase (1-3 days) “local GIT irritation” and generalized herbicide “depression” Causes edema ulcers in GI tract and in brain, has been shown to damage dopaminergic neurons can into BBB by specific protein carrier gets taken in by accident, because its thought of to be a nutrient can cross the BBB by spcific carrier LAT-1 and causes oxidative damages to dopamine complex Collects in the lungs, liver and kidney Mechanism of Toxicity 1. General chemical (herbicide toxic...
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This document was uploaded on 04/07/2014.

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