Mercury Arsenic and Lead Flashcards
Forms of Mercury
Elemental:Stuff found in thermometers. Liquid at room temp Forms vapor (Hg) that are much more toxic
Inorganic: mercury bound to other elements
Often combo with chloride(Hg+ Cl-)
Organic:
Methlymercury - fish
Dimethylmercury - a few millilitres can kill and pass thru skin
Elemental mercury
Hg vapor- extremely hazardous- Absorbed via lungs(80%) - but poorly absorbed if swallowed as liquid.
Catalase in RBC convert it into inorganic or divalent form- rapidly trapped once in CNS and accumulates=toxic
IF enough accumulates, get symptoms similar to inorganic poisoning
Inorganic
Found as metallix mercury(Hg) or as salts in 2 states-toxic and corrosive
Hg+
Hg2+
Primary route of entry is oral, but poorly absorption(10%), but can also enter skin
Tend to accumulate in the renal tubules via OATs-AKI
Little CNS penetration bc low lipophilicity
Ex. Cinnabar- mercury sulfide
Organic
Found in 3 forms
Aryl
Short chain alkyl
Long chain alkyl-rare
High lipid soluble so absorbed readily through GI (50-90%) and distributed to most organs and will cross the BBB and placenta
Accumulate in brain via neutral amino acid carrier
Post aborption converted into inorganix form and has similar properties to inorganix mercury
Ex. Methlymercury has hi aff for SH groups where it replaces the hydrogen-fish
Dimethyl form kills ez if enters skin
Hg toxicity
Elemental: Acute local effects-bronchial irritation, pneumonitis, fatal
-mercury vapor triad: Tremors, gingivitis and erethism(memory loss, inc excitability, insomnia, depression, shyness)
Inorganic: Abdominal pain, nausea, vomiting, diarrhea
- Kidney-acute binding to thiols-necrosis of epithelial cells in prox tubule ATN
- Chronic low doses : immunological glomerular disease(autominnume), proteinuria(HMW)
Organic: primarily NEUROTOXICITY- cortex and cerebellum most affected
-paresthesia(numbness and tingling around mouth and lips) ataxia, general weakness, progression to coma and death
-cerebral edema, destruction of grey matter, cerebral atrophy
Dose response curve methylmercury: low to hi conc: paresthesia, ataxia, dysarthria, deafness, death
Hg mechanism of toxicity:
3 major mech:
Inc intracell Ca2+ levels: release intracell store via Muscarinic receptor activation on ER + inc entry through memb-bound channels
Covalent mod of SH groups on enzymes
Inc. oxidative stress by either inc ROS production(NOT FENTON) or decrease GSH
Result: cell death by apop or necrosis-depend on level of exposure (hi=necro, low=apop)
Managing Hg poisoning
DMPS:oral chelator considered first line by WHO for inorganic
Can penetrate into kidney cells and remove mercury deposited in some tissue(BUT NOT BRAIN) although some evidence for decrease neurotoxicity in chronic
Cause an initial spike in pee(release mercury from stores) followed by a decrease-can measure mercury level through hair, blood(constant decrease and surgical removal) and urine
BAL(british anti lewisite)- for inorganic but NOT ORGANIC
Can remove inorganic from kidneys
Injections are painful
Penicillamine(B,B,dimethlycysteine): Chelator for methylmercury and mercury vapour(elemental and organic;))
Arsenic
Used today in pesticides, herbicides and metal production. Effective drug for certain leukemias.
Trivalent(monomethyl) is most toxic, pentavalent(dimethyl) is excreted
Arsenic Absorption
Effectively absorbed VIA GIT(80-90%)
Ineffectively abs through skin
Can lose arsenic when skin sheds or via sweating and will have hi conc in hair and fingernails(Mee’s lines-white line same position across all fingernails)
Arsenic Poisoning
Acute: ingestion of 70-180mg=fatal
Fever, anorexia, hepatomegaly, cardiac arrhythmia
Damage to mucous membranes of GIT
Sensory loss 1-2 weeks after initial exposure(reversible)
Chronic: skin is major target in chronic***
Pigmentation change(Rain drop pattern), hyperkeratosis, alopecia
Bone marrow suppression, anemia
Symmetrical sensorimotor polyneuropathy is classical symptom of chronic
Inc. rate of skin, lung, liver and GIT cancer
Mech of As toxicity
Trivalent is highly reactive with protein SULFHYDRYL GROUPS
Interfere w/ pyruvate dehydrogenase complex-no acetyl-CoA formation =Decrease TCA
Disruption of oxidative phosphorylation = ROS production
Pentavalent forms appear to replace phosphate
Arsenolysis-arsenic ions replace phosph in high E comp-instead of ATP form, ADP-arsenate instead = ATP decrease result in cell death
Arsenic in general inhib over 200 diff enzymes
Arsenic in general induces MPT and cause apop and necro
Cancer(MOSTLY TRIVALENT): Alter DNA methylation state-impaired DNA repair, chromosomal abnormalities
Arsenic poisoning treatment
Acute-Penicillamine or DMSA to chelate + increase renal excretion
Chronic- no evidence that chelate have any effects. Reduce exposure is best strategy
Lead
Interferes with heme biosynth: ANEMIA
Most sensitive to inhibition are ALAD-cytoplasm(Sigma-aminolevulinic acid dehydratase)ALA to porphobilinogen and ferrochelatase-mitochon-protoporphyrin to heme
Result: depressed hematocrit. NET RESULT inc ALA, inc protophorphyrin
Anemia in severe cases RBC end with protoporphyrin chelated to zinc instead of hemoglobin chelated to iron.
Burton’s line: A bluish-purple line at the interface of gums and teeth
- reaction of lead with sulphur ions release by oral bacteria=sulphide deposition
- The worse the oral hygiene, the thicker the line
SEE PIC
Pb neurotoxicity in children
encephalopathy in children
lethargy, vomiting, ataxia, reduced consciousness
edema due to extravasation of fluids from brain aps
loss of neuronal cells and increase glial cells
Primary seems to affect prefrontal cortex, hippocampus and cerebellum
Pb neurotox in adults
Peripheral neuropathy is classical symptom
Footdrop and Wristdrop used to occur in lead-based painters
Neuropathy is characterized by segmental demyelination and axonal degeneration
