Principles Lec 4 2013

Specific transporters proteins sugars essential


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Unformatted text preview: oteins, sugars, essential vitamins) 2. lipophilic substances (Anaesthetics) o T add more distance that compound needs to travel o T o o +- T T +- T T o T T+- T+T+- T+- Blood Brain Barrier Endothelial cells form the tight junctions Glial cells, astrocytes secrete chemical factors, control permeability Also structural role in maintaining integrity of BBB NO absorption of water soluble chemicals Also regulated xenobiotic transporters that keep lipid soluble chemicals out (efflux pumps) Low protein content in CSF, limits transport of bound toxins adds extra element of control provide extra fatty layer you have to travel across pump things out that you dont need Astrocytes can be mistakenly taken in if attached to BBP Glial Cells CSF certain pumps bring things in, and these can be where bad things get in Blood Placental Barrier (BPB) Placenta fulfills many roles for the infant Nourishment, Protection, gas exchange, get rid of waste BPB Contains many cell layers, differentiates between mother and fetal blood Active transport of essential molecules, diffusion of toxins Efflux transporters, Metabolising enzymes limit toxicant movement 4-5 cell layers to increase diffusion distance Not as Robust as BBB! Blood Placental Barrier • Specific transporters transporter expressed on tissue speciﬁc side •Bring in nutrients •Pump toxins and toxic metabolites out (extra layer of protection) •Increases elimination Diethylstilbestrol- next generation carcinogen can cross BPB Blood-Testis Barrier Not many testicular specific toxins exist Sertoli Cells (make up the barrier) keep things out and keep things in Provide “barrier, nurture and develop growing spermatocytes Tight junctions between cells doesn’t allow paracellular transport Stops diffusion between cells As much a barrier to escape as entrance Auto-immunity to sperm cells Toxins include Pthalate esters, glycol ethers, antiandrogenic agents Storage of Chemicals in Body K1 K2 Storage of Chemicals in Body Concentrate and hold chemicals in tissue Tissue factors that favour storage: a. Lipid nature (adipose tissue, neural tissue) b. pH c. Specific transport mechanisms d. Binding or incorporation of chemicals into tissue Storage of Chemicals in Body Examples of organs / tissues: polycholornated biphenols 1. Adipose tissue (e.g. PCBs)- very fatty - Like dissolves like, stay in favorable environment (Kow) - becauseaitcutetotoxicity, when fat store mobilized can’t go site of action - Decrease to exercise BFI due 2. Bone (e.g. Pb2+) Incorporated in matrix instead...
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