Cadmium Flashcards
where is most cadmium that is produced go/used for
in batteries
besides batteries, what is another source of Cd
food because plants actively accumulate it
-shellfish and animal livers
what is something that can double the body burden of cadmium
smoking (over a lifetime)
what % is GI absorption of Cd
5-10%
how is Cd absorbed in the GI
divalent metal ion transporter 1 (DMT1) that normally transports Mn Co Zn, Pb and Ni
which people on which diets get increase Cd absorptions
people with low iron diet because DMT1 is upregulated
do men or women have more DMT1
women
what is the % of absorption through inhalation
35%
what size particles are most dangerous for Cd and why
smaller particles because it can penetrate to alveoli where it is almost 100% transference into blood
where is Cd primarily deposited
in the liver and some in kidneys
is the liver or kidneys more sensitive to effects of Cd
the kidneys
what are 5 acute Cd toxicity symptoms
painful sphincter spasms, excess salivation, bloody diarrhea, pneumonitis with pulmonary edema
what can happen with inhalation of large Cd doses
death
what are 4 body systems that are effected with Cd chronic toxicity
kidneys, lungs, bones and heart
what happens to the kidneys with Cd chronic toxicity
proximal tubular damage so increased SMW proteins
what happens to the lungs with Cd chronic toxicity
obstructive pulmonary disease - fibrosis, emphysema
what happens to the bones with Cd chronic toxicity
osteoporosis/ osteomalacia - spontaneous fractions
why do you get osteoporosis/ osteomalacia - spontaneous fractions with Cd chronic toxicity (2)
loss of VitD binding protein and renal calcium reabsorption issues
what happens to the heart with Cd chronic toxicity
cardiovascular disease, toxic to myocardium
what is a main bad thing that can happen with Cd chronic toxicity
cancer
what is the main mechanism of Cd++ toxicity
bidns to sulfhydryl groups of proteins
which type of proteins does Cd++ differentially affect
mitochondrial proteins
what other type of proteins does Cd++ affect (besides the mitochondrial proteins)
function of adhesion proteins (esp in tubule cells)
what kind of transport does Cd++ affect
glucose transport
how does Cd++ affect glucose transport
downregulation of Na+ dependent glucose transporter expression due to substitution for Zn++ in a transcription factor (Sp1)
how does Cd++ cause mitochondrial toxicity
depletion of antioxidant thiols causing oxidative stress
what happens once Cd++ causes oxidative stress in mitochondria
induce MPT, release cyt C, apoptosis
how does Cd++ cause carcinogenesis
affects enzyme that methylates DNA (DNMT1) may alter transcription of tumor suppressor genes
what is metallothionein
a protein found in many tissues including kidney, liver, spleen, heart, lung and brain
what induces metallothionein expression
Cd++ Zn++ Hg++
what does metallothionein do
binds and sequesters Cd++, Zn++ and Hg++
what is the half life of metallothionein bound Cd
10-30 years
is metallothionein bound Cd toxic
no
what does Cd++ do at high levels (what does it bind to)
GSH
what does Cd++ do at low levels (what does it bind to)
metallothionein
what happens when Cd enters the liver cell
it can bind to GSH or MT
what happens once the liver cell dies and Cd-MT is in it
it can leave as Cd-MT into the urine or it can enter the renal cell
what happens when Cd-MT enters the renal cell (4)
enters lysosome, MT is broken down into aa, then CD is release, and free Cd can interact with sulfhydryl groups in mitochondria to damage
what is the main protocol for cadmium poisoning
there is none, mostly supportive care (chelators are ineffective)
what does EDTA do to Cd poisoning
maybe beneficial in single dose causes, increased nephrotoxicity after repeated Cd exposure
what does BAL do to Cd poisoning
increases nephrotoxicity, increases uptake by kidneys
when is DMSA used for Cd poisoning
if cadmium was ingested to help prevent further absorption
what is an issue with chelation therapy and Cd
it may act to redistribute cadmium to other organs by stripping it away from metalothionein (then its free to cause damage)
what may be a thing that helps reduce cadmium and sulfhydryl group interactions
conjugation with glutathione
what is the mechanism of GSH helping with Cd toxicity
Cd normally binds to sulfhydryl groups on proteins leading to denaturation/inactivation, so then now Cd binds to GSH
what is something that GSH can be administered to help with Cd
give EDTA to prevent escalating toxicity
