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Lecture 5

TOX 2000 Lecture Notes - Lecture 5: Hoogsteen Base Pair, Homeostasis, Caesium

Course Code
TOX 2000
Aaron Witham

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Lecture #5 November 9, 2012
Review Questions
- Excessive consumption of fat-soluble vitamins may be toxic because they are not
easily eliminated (B)
- toxicity associated with fluorosis involves brittle teeth and bones (D)
Removal of Chemicals from the Body
- excretion and biotransformation (metabolism) work in tandem to eliminate
exogenous toxicants
- main routes:
o kidney urine (aqueous)
deals with molecular weight chemicals
o liver/bile fecal (lipids and aqueous)
deals with molecular weight chemicals
- characteristics favoring excretion:
o lipid solubility
o ionized and water soluble
o free toxin = non-protein bound
Mechanisms of Excretion
- filtration
o renal urine
- active secretion
o kidney urine and liver bile
- diffusion into glandular secretions
o mammary, sweat, saliva
- these mechanisms can fail:
o lipid-soluble soluble bioaccumulation
o reabsorbed
kidney (Hg-metalothionine)
GIT (bile salts)
active transport
o binding storage bioaccumulation
The Kidney
- nephrons (1 million) glomerulus
- high blood flow
- leaky podocytes
- spaces 40 angstroms
o 1A = 1/100000000 cm
- hydrostatic filtration: hydrophilic chemicals are pushed through
- water, sugars, and peptides are reabsorbed
o transport mediated
- some transporters contribute to secretion
- balance between influx and efflux

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Liver Anatomy
- receives oxygenated blood from the heart via the hepatic artery
- receives blood from the stomach, SI, LI, pancreas, and spleen via the portal vein
- tissue is divided into lobules and portal triads
o lobules: hexagonal
o portal triads: divisions on corners
- hepatocytes lines sinusoids
o hepatic capillaries
- bile ducts are arranged to collect fat-soluble waste
o drain into the gall bladder

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Liver Secretion
- liver is the first target of the molecules absorbed from the GI tract
- liver is a major site of metabolism
o many xenobiotics transporters filter blood and import molecules
- hepatocyte functions:
o synthesize bile
o secrete conjugates into bile
bile drains into the gall bladder and ends up back in the intestine
Billiary Excretion
- bile salts: compounds that emulsify fats by breaking down large globules for
easier digestion
o composition similar to detergents:
both lipophilic and hydrophilic characteristics
o size is very important
- compounds are divided into three categories based on the ratio of biliary to
plasma secretion
o ratios close to one glucose, mercury, thallium, cesium, sodium
o ratios greater than one bile acids, bilirubin, lead, many xenobiotics
o ratios less than one insulin, albumin, zinc, iron, gold
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