Cadmium

Question 1

where is most cadmium that is produced go/used for

Answer 1

in batteries

Question 2

besides batteries, what is another source of Cd

Answer 2

food because plants actively accumulate it

-shellfish and animal livers

Question 3

what is something that can double the body burden of cadmium

Answer 3

smoking (over a lifetime)

Question 4

what % is GI absorption of Cd

Answer 4

5-10%

Question 5

how is Cd absorbed in the GI

Answer 5

divalent metal ion transporter 1 (DMT1) that normally transports Mn Co Zn, Pb and Ni

Question 6

which people on which diets get increase Cd absorptions

Answer 6

people with low iron diet because DMT1 is upregulated

Question 7

do men or women have more DMT1

Answer 7

women

Question 8

what is the % of absorption through inhalation

Answer 8

35%

Question 9

what size particles are most dangerous for Cd and why

Answer 9

smaller particles because it can penetrate to alveoli where it is almost 100% transference into blood

Question 10

where is Cd primarily deposited

Answer 10

in the liver and some in kidneys

Question 11

is the liver or kidneys more sensitive to effects of Cd

Answer 11

the kidneys

Question 12

what are 5 acute Cd toxicity symptoms

Answer 12

painful sphincter spasms, excess salivation, bloody diarrhea, pneumonitis with pulmonary edema

Question 13

what can happen with inhalation of large Cd doses

Answer 13

death

Question 14

what are 4 body systems that are effected with Cd chronic toxicity

Answer 14

kidneys, lungs, bones and heart

Question 15

what happens to the kidneys with Cd chronic toxicity

Answer 15

proximal tubular damage so increased SMW proteins

Question 16

what happens to the lungs with Cd chronic toxicity

Answer 16

obstructive pulmonary disease - fibrosis, emphysema

Question 17

what happens to the bones with Cd chronic toxicity

Answer 17

osteoporosis/ osteomalacia - spontaneous fractions

Question 18

why do you get osteoporosis/ osteomalacia - spontaneous fractions with Cd chronic toxicity (2)

Answer 18

loss of VitD binding protein and renal calcium reabsorption issues

Question 19

what happens to the heart with Cd chronic toxicity

Answer 19

cardiovascular disease, toxic to myocardium

Question 20

what is a main bad thing that can happen with Cd chronic toxicity

Answer 20

cancer

Question 21

what is the main mechanism of Cd++ toxicity

Answer 21

bidns to sulfhydryl groups of proteins

Question 22

which type of proteins does Cd++ differentially affect

Answer 22

mitochondrial proteins

Question 23

what other type of proteins does Cd++ affect (besides the mitochondrial proteins)

Answer 23

function of adhesion proteins (esp in tubule cells)

Question 24

what kind of transport does Cd++ affect

Answer 24

glucose transport

Question 25

how does Cd++ affect glucose transport

Answer 25

downregulation of Na+ dependent glucose transporter expression due to substitution for Zn++ in a transcription factor (Sp1)

Question 26

how does Cd++ cause mitochondrial toxicity

Answer 26

depletion of antioxidant thiols causing oxidative stress

Question 27

what happens once Cd++ causes oxidative stress in mitochondria

Answer 27

induce MPT, release cyt C, apoptosis

Question 28

how does Cd++ cause carcinogenesis

Answer 28

affects enzyme that methylates DNA (DNMT1) may alter transcription of tumor suppressor genes

Question 29

what is metallothionein

Answer 29

a protein found in many tissues including kidney, liver, spleen, heart, lung and brain

Question 30

what induces metallothionein expression

Answer 30

Cd++ Zn++ Hg++

Question 31

what does metallothionein do

Answer 31

binds and sequesters Cd++, Zn++ and Hg++

Question 32

what is the half life of metallothionein bound Cd

Answer 32

10-30 years

Question 33

is metallothionein bound Cd toxic

Answer 33

no

Question 34

what does Cd++ do at high levels (what does it bind to)

Answer 34

GSH

Question 35

what does Cd++ do at low levels (what does it bind to)

Answer 35

metallothionein

Question 36

what happens when Cd enters the liver cell

Answer 36

it can bind to GSH or MT

Question 37

what happens once the liver cell dies and Cd-MT is in it

Answer 37

it can leave as Cd-MT into the urine or it can enter the renal cell

Question 38

what happens when Cd-MT enters the renal cell (4)

Answer 38

enters lysosome, MT is broken down into aa, then CD is release, and free Cd can interact with sulfhydryl groups in mitochondria to damage

Question 39

what is the main protocol for cadmium poisoning

Answer 39

there is none, mostly supportive care (chelators are ineffective)

Question 40

what does EDTA do to Cd poisoning

Answer 40

maybe beneficial in single dose causes, increased nephrotoxicity after repeated Cd exposure

Question 41

what does BAL do to Cd poisoning

Answer 41

increases nephrotoxicity, increases uptake by kidneys

Question 42

when is DMSA used for Cd poisoning

Answer 42

if cadmium was ingested to help prevent further absorption

Question 43

what is an issue with chelation therapy and Cd

Answer 43

it may act to redistribute cadmium to other organs by stripping it away from metalothionein (then its free to cause damage)

Question 44

what may be a thing that helps reduce cadmium and sulfhydryl group interactions

Answer 44

conjugation with glutathione

Question 45

what is the mechanism of GSH helping with Cd toxicity

Answer 45

Cd normally binds to sulfhydryl groups on proteins leading to denaturation/inactivation, so then now Cd binds to GSH

Question 46

what is something that GSH can be administered to help with Cd

Answer 46

give EDTA to prevent escalating toxicity