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Reading Casarett and Doull Chapters 5 and 7 Timbrell, Chapter 3 EXPOSURE: Absorption, Distribution, Elimination. Or, how do chemicals (and microbes) get.

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Presentation on theme: "Reading Casarett and Doull Chapters 5 and 7 Timbrell, Chapter 3 EXPOSURE: Absorption, Distribution, Elimination. Or, how do chemicals (and microbes) get."— Presentation transcript:

1 Reading Casarett and Doull Chapters 5 and 7 Timbrell, Chapter 3 EXPOSURE: Absorption, Distribution, Elimination. Or, how do chemicals (and microbes) get into, around and out of our bodies

2 Routes of Exposure Airborne – inhalation –Respiratory tract, nose-lungs Foodborne – ingestion –Gastrointestinal tract Skin Contact - transdermal Waterborne Injection –Wounds, needlesticks

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4 The plasma membrane Lipid bilayer Polar Non-polar (Lipid) Protein Av. Width 7.5 nm (75 Å) Sugar Glycolipid Glycoprotein

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6 Mechanisms of uptake Passive diffusion Filtration Carrier-mediated transport –Facilitated diffusion –Active transport Engulphment –Pinocytosis –Phagocytosis

7 Uptake Higher concentration Lower concentration Diffusion Filtration Pore Lipid bilayer Carrier Facilitated diffusion Active transport

8 Engulfment

9 Engulphment

10 Microbes Host cell receptors – glycolipids, glycoproteins or proteoglycans Microbial pili, fimbriae, adhesins – lectins, hemagglutinin

11 Factors influencing route and rate of uptake Properties of the chemical –Size and shape –Similarity to “endogenous” molecules –Solubility Hydrophilicity/hydrophobicity Lipophilicity/lipophobicity Partition coefficient: K ow –Log 10 of [octanol]/[water] –Charge Ionization state

12 For an acid: HAH + + A - –Henderson-Hasselbach equation: pH = pK ’ + Log 10 [A - ]/[HA] For a base: BH + B + H + –Henderson-Hasselbach equation: –pH = pK ’ + Log 10 [B]/[BH + ]

13 Properties of the membrane/tissue/organ –Presence/absence of pores –Presence/absence of carrier molecules –Thickness –Lipid content Factors influencing route and rate of uptake Carrier

14 Skin

15 Surface area approximately 2 m 2 Multilayered –Epidermis Stratum corneum Living epidermis –Dermis Blood circulation

16 Respiratory Tract

17 Respiratory tract Surface area approximately 50 to 100 m 2

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19 Gastrointestinal tract Surface area approximately 600 m 2

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21 Intestinal wall - villi

22 Cross-section of villus

23 Placenta

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25 Distribution Factors affecting tissue localization Plasma proteins Barriers to distribution –Blood-brain barrier –Blood-nervous system barrier Factors that facilitate distribution –Sinusoids –Trans-membrane carriers

26 Location (In)ability to detoxify/clear infection Specific susceptibility – receptors, metabolic characteristics

27 Excretion Routes of elimination –Urine –Bile –Feces –Exhaled air –Sweat –Tears –Milk –Leaves

28 The Kidney

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30 Lung again

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32 Excretion Routes of elimination –Urine –Bile –Feces –Exhaled air –Sweat –Tears –Milk –Leaves


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