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502 final - heavy metals

Terms in this set (21)

Metallothionein
Endogenous protection against metal toxicity
Metal detoxification and homeostasis
Transferrin receptor
Brings metals across BBB
Normally high affinity for iron
Mercury
3 chemical forms
Natural in environment
Biomarkers-hair, blood, others
Dose response
Cross BBB, placental barrier, lipid soluble, concentrates in kidney, GI absorption
Metallic/elemental Mercury
Hg 0
Inhalation
Lipid soluble
Crosses BBB
Targets: pulmonary, some CNS
35 to 90 day half life
Inorganic/mercuric Mercury
Hg 2+ or Hg 1+
Ingestion
40 day half life
Targets: GI and renal
Peripheral problem
Damage PCT (b0 active transporter Hg bound to cysteine- homocysteine)
Organic Mercury
Not charged
Ingestion or inhalation
Affects fetus the most
Targets: CNS the most, PNS, renal
70 day half life
Dialkylated
Minamata disease
CNS and PNS degeneration
Tingling and numbness
Impaired motor function, vision, speech
Mercuric chloride and methyl mercury
Cadmium
2+ state
Potent renal toxicant
Sources: mining, food and water, fertilizers, tobacco
Ingestion
20 to 30 year half life (kidney)
Targets: lung, kidney, bone
Cadmium biomarkers
Urine content, glucose, proteinuria
Cadmium MOA
Free causes damage
Oxidative damage
ROS
Bound to metallothionein increases half life goes to kidney and frees it or is excreted
Itai-itai disease
Cadmium chronic toxicity from water
Bones soft and fragile, excessive osteon
Kidney thin cortex
Females affected
Chelator
Binds metals with high affinity
Therapies for metal toxicity
Nrf2
Transcription factor
Induces phase 2 enzymes-GST, NQO1, GSH reductase, SOD
Protective against oxidative stress and cell damage
Lead
Major Source: drinking water
Absorb into bones and teeth
Blood circulation
Children absorb more than adults
Target: brain, nervous system
>10 ug/dL lead
Risk: 1
Effect: none
10-14 ug/dL lead
Risk: 2, moderate
Effects: IQ deficits, ALA-D (alanine synthesis) inhibition
15-19 ug/dL lead
Risk: 2 moderate
Effects: developmental
20-44 ug/dL lead
Risk: 3 high
Effects: increased U-ALA, PNS/CNS impairment, vitamin D metabolism
45-69 ug/dL lead
Risk: 4 urgent
Effects: nephropathy, colic
<70 ug/dL lead
Risk: 5 emergency
Effects: encephalopathy, rapid anemia
Lead MOA
Impaired Ca 2+ entry into the cell, loss of synaptic function and pathway formation, inhibits neurogenesis in adult brain
Interrupts heme biosynthesis energy metabolism in mitochondria
Threshold dose