Trace Elements Flashcards
organic lead
tetraethyllead
exposure =rare since advent of unleaded gas
differ from signs of inorganic lead poisoning in that hematologic abnormalities are unusual and encephalopathy predominates
metabolized to inorganic lead so if chronic exposure will eventually present as same problems as inorganic lead exposure
mercury poisoning
used in dent, med (diuretics), ag, and industry (electrical components)
can be divided into three chemical classes:
> inorganic mercury salts (mercuric and mercurous salts)
> elemental mercury
> organic mercury salts (arylmercury and alkylmercury)
inorganic mercury released by industries into waterways can be converted to methylmercury by microflora
symptoms of mercury poisoning
chronic exposure to mercury produces significant effects on two organ systems: CNS & kidneys
elemental mercury poisoning
high lipid solubility and crosses cell membranes
chronic inhalation of merc vapour, mercury will preferentially attack CNS
crosses blood-brain barrier and accumulates in CNS
after rapidly accumulating in the brain, the mercury oxidizes to the mercuric form
cause degenerative changes through action on structural proteins and enzyme systems; synaptic and neuromuscular transmission is blocked
all mercury compounds will concentrate in the kidney to some extent
organic mercury poisoning
- crosses BBB and placenta causing neurological and teratogenic disorders
- 90% of a methylmerucry ingestion is absorbed compared to 10% with the soluble inorganic salts
- organic mercury is less corrosive to intestinal mucosa than inorganic mercurials
- the alkylmerucry compounds are almost completely absorbed from the GI tract - distributed to brain (target organ), liver and kidney and excreted primarily in the feces
chronic arsenic toxicity
malignant changes in almost all organs of the body
exact mechanism of carcinogenesis unknown
effective treatment of chronic exposure not yet established
arsine gas
- rapid and fatal hemolysis is a unique characteristic (since cmombnies w Hb, reacting with oxygen to cause hemolysis)
classic arsine triad = hemolysis, abdominal pain, hematuria
jaundice after 24hrs
coppery skin pigmentation = due to metheme perhaps??
if patient survives hemolysis - death may result from renal failure (necrosis of proximal tubule)
at high levels produce direct multi-system cytotoxicity
cadmium poisoning
one of heavy metals of greatest toxicological concer
exposure due to electroplating, pigments, plastic stabilizers, batteries
found in nature with lead and zinc;during mining of these metals, cadmium may be released into air
poorly absorbed din GI tract = little as 5% entering blood
comes form contaminated food and water
inhalation of airborne cadmium from cigarette smoking
heavy metal most prone to accumulate in body
cadmium
bio half-life of cadmium
10-30 yrs
kevel increases throughout life
where does cadmium accumulate?
lung, liver, kidney
what enzymes does cadmium inhibit?
enzymes containing sulfhydryl groups
- binds to other ligands on proteins and purines
also inhibits alpha1-antitrypsin = responsible partly for pulmonary symptoms
cadmium competes with cellular uptake of various other metals in body such as _______ & _____
copper; zinc
oral symptoms of cadmium toxicity
severe nausea, diarrhea, vomiting
muscular cramps
salivation
dizziness
proteinuria
glycosuria
osteomalacia
inhalation symptoms of cadmium toxicity
rhinorrhea
difficulty breathing
chest pain
pulmonary edema
progressive emphysema
azotemia (presence of ura & other nitrogenous bodies in blood)
proteinuria
liver necrosis
symptoms of cadmium toxicity
- severe cadmium poisoning in residents of Toyoma, Japan due to contamination of rice fields by cadmium released from a metal poisoning plant upstream
- renal damage leading to disturbances in calcium and phosphorus metabolism were believed to be responsible for skeletal abnormalities and severe leg and back pain
essential elements needed for normal physiological functionig
chromium
cobalt
copper
manganese
molybdenum
selenium
vanadium
zinc
sources of zinc
oytsers
red meat
pultry
cheese
shellfish
legumes
whole grains
mushrooms
brewer’s yeast
sources of copper
oysters
liver
whole grains
shellfish
legumes
nuts
choclate
sources of chromium
bbrewer’s yeast
lean meats
cheeses
whole grains
mmolasses
spices
bran cereals
sources of selenium
rbazil nut
brewer’s yeast
liver
butter
fish
shellfish
garlic
whole grains
functions of zinc
protein synthesis
carbohydrate metabolism
zinc dependent enzymes = alc dehydrogenase
acts as an antioxidant and free radical scavenger
gatekeeper of immune response
symptoms of zinc deficiencies
growth retardation
delayed sexual maturation
anorexia with altered taste and smell
acrodermatitis (inflam of skin - hands or feet)
impaored wound healing + immunity
alteration of vitamin A emtabolism
acrodermatitis enteropathicaa
inherited as an autosomal recessive trait attributed to a defect in zinc metabolism
after weaning from breastfeeding = babies get pustular dermatitis combined with severe GI disturbances
zinc supplementation = free of symptoms
this is widely used in galvanizing processes, paints, preserving wood, and alloy agent in brass
Zinc
this is used in medicinal preparations as topical astringents, antiseptics, antifungal agents and as lozenges for common col
zinc salts
metal fume fever
inhalation of freshly formed fumes of zinc oxide (eg. welding, metal cutting)
half life of zinc
5-16 months
zinc poisoning symptoms
oral = lassitude (tiredness, listlessness), enteritis, diarrhea (bloody or watery), intense ab pain, CNS depression, tremors
inhaltion = sudden onset of thirst, fever, chills, myalgias (musc headached and pains), headaches
zinc chloride fumes have caused death due to such complications as ________ ________ and ______________
pulmonary edema; bronchopneumonia
functions of copper
constituent of enzymes and proteins
necessary for Hb synthesis
component of superoxide dismutase = scavenges free radical superoxide (O2-)
symptoms of copper deficiencies
disorders in pigmentation
retarded growth
anemia in children
arterial wall structure defect
Menkes’ disease
steely or kinky hair syndrome = sex-linked recessive disorder of copper absorption
extremely low level of copper
name of disease = defective keratinization and pigmentation of hair
bone changes, severe cerebral degeneration (early infancy, failure to thrive, lethargy, hypothermia, seizures)
sopper supplementations allows clinical improvement (parenteral administration; other routes than digestive tract)
Wilson’s disease
hepatolenticular degeneration
severe autosomal recessive disorder of copper metabolism
onset = 4-5 yrs
diminished synthesis of copper-transporting protein ceruloplasmin and impaired excretion of copper into bile
copper low in serum but high in urine
zinc therapy used to prevent copper absorption
what happens when copper accumulates in liver?
cirrhosi
what happens when copper accumulates in brain?
destruction of nerve cells
what happens when copper accumulates in kidney and cornea?
Kayser-Fleischer rings
algicide
copper sulfate
copper poisoning
- electrical wiring
- algicide
- acute oral ingestion of copper salt or food contam by copper utensils
- industrial exposure due to inhalation of copper fumes or dust
half-life of copper
26 days
acute exposure of copper: symptoms of poisoning
nausea, vomitting
bloody diarrhea
hypotnesion
hemolytic anemia
uremia
CV collapse
chronic exposure of copper: symmptoms of poisoning
sporadic fever
comiting
epigastric pain
diarrhea
jaundice
inhalation of copper: symptoms of poisoning
metal fume fever
ulceration and perforation of nasal septum
necrotic hepatitis
functions of selenium
biologically active part of proteins, esp enzymes involved in antioxidant defense mechanisms (glutathione peroxidases), thyroid hormone metabolism (deiodinase enzymes), redox control of intracelular rxns (thoredoxin reductase)
thisi s reported to reduce the toxicity of many metals including mercury, cadmum, lead, silver, and to some extent, copper
selenium
symptoms of selenium deificencies
heart disease
hypothyroidisim
weakened immune system
this is associated with two endemic diseases found in China
selenium-poor regions
Keshan Disease
Kashin-Beck Disease
Keshan Disease
cardiomyopathy = cardiac enlargement, abnormal ECG, cardgiogenic shock, CHF, necrosis of myocardium
Acute Keshan Disease
nausea
vomiting
necrosis of myocardium
T or F. Keshan disease is reported to occur primarily in children and women of child-bearing age
T!
how do we treat Keshan disease?
selenium supplementation
Kashin=Beck disease
atrophy, degeneration, and necrosis of cartilage tissue
occurs in children 5-13 years of age
treat with selenium supplements
factors other than selenium could be at work
coal combustion
selenium
selenium poisoning
ubiquitous
coal combustion
potographic devices, plastics, paints, anti-dandruff shampoo, vitamin, mineral supplements, fungicides, types of glass, feed supplement for pultry and livestock
half life of sleenium
100 days
respuiraotry symptoms of selenium
dizziness, fatigue, irritaiton of mucus membranes
extreme caes = pulmonary edema and severe bronchitis
acute oral exposure symptoms of selenium poisoning
nausea, voiting, diarrhea
ocassionally = CV symptoms such as tachycardia
chronic oral exposure of selenium
selenosis
dermal = loss of hair, deformation/loss of nails (white spots, streaks, breaks off easily), discoloration + excessive decay of teeth
neurological = numbness, paralysis
marker of over-exposure to selenium compounds
garlic breath
sources of lead exposure
water, air, soil, food (ENVIRONMENTAL)
crayons, toys, paper, clothes, dirt, sand, paint flakes, plastics, etc. (HOUSEHOLD)
miners, smelters, automobile finishers, storage battery workers, sheet metal workers, spray painters (HIGH INDUSTRIAL RISK)
over 90% of asorbed lead is deposited here
bone
lead poisoning
- cumulative = both acyte and chronic intoxication
- acute poisoning rare; chronic more common and serious
- manifestation of toxicity = binding sulfhydryl groups of protein molecules = inactivates enzyme systems such as production of heme
half life of lead
0.4-3.6 yrs
symptoms of acute lead poisoning
uncommon
lead dust
non-specific; GI inflammation
urinary output decreases due to renal damage
massive ingestion may cause death due to CV collapse
plumbism
chornic lead poisoning
hematological symptoms of chronic lead poisoninh
baso stoppling
anemia
GI symptoms of chronic lead poisoning
anorexia
constipation
metallic taste
neurological symptoms of chronic lead poisoning
lead encephalopathy
ataxia, nausea, vomiting
restlessness
irritability
convulsions
coma
neuromuscular symptoms o chronic lead poisoning
lead palsy
wrist drop, foot drop
fatigue
muscular weakness
renal symptoms of chronic lead poisoning
impaired tublar reabsorption of glucose, phosphate, AAs, bicarbonate
irreverisble chronic nephritis
lead levels of concern in children
5 ug/dL or 0.24 umol/L
why are children susceptible to neurotoxicity from lead
elevated GI absorption (they absorb 50% and retain 30%)
they also have incompletely developed BBB that do not prevent CNS entry
T or F. 1/4 of lead encephalopathy victims will not survive
T
> 40% of survivors experience intense neurological dysfunction
generalized CNS toxicity in children due to lead
- shorter attention span
- impulsiveness
- cant follow directions
- inappropriate provlem solving
- robust deficits in learned skills
T or F. Lead poisoning is a notifiable disease
T
lead levels of ____ are notifiable
greater than 0.5 umol/L
toxic effects of mercury dependent on:
chemical form
route of admin
duration of exposure or amount
imdividual sensitivity
chronic exposure to mercury produces significant effects on two rogan systems
CNS
kidney
T or F. Mercuric salt (HgCl2) is more toxic than mercurous salt (Hg2Cl2)
T
ifi ngested, HgCl2 mo,re rapidly absorbed and greater toxicity
T or F. Monovalent inorgnic mercury salts are more soluble than divalent
F! divalent more soluble
This is the principle target organ for inorganic mercurials
kidney
symptoms of inorganic mercury exposure
- immediate corrosive injury to mouth mucosa, throat, esophagus and stomach (INGESTION)
- mouth, pharynx and gastric mucosa appear ashen and painful
- profuse vomiting of mucoid mateiral, bloody diarrhea, circulatory collapse, shock and sudden death
- tubular necrosis
“mad as a hatter”
mercuric nitrate = felt hat industry
neurological changes due to exposure
sy,ptoms of elemntal mercury exposure
nonspecific = anorexia, weight loss, fatigue, muscular weakness
(inhalation or absorption through skin)
neurological/behavuioural problems frmo accumulation in cerebral/cerebellar cortex
= tremors in fingers, eyes or tongue => entire limp, slurred speech, illegible handwriting, anger attacks, high irritability, memory loss, drowsiness, loss of interest in life +{ withdrawal from society(erethism)
limited tubular necrosis
T or F. Organic mercurials cross BBB and placenta
T = neurological and teratogenic disorders
T or F. Organic mercury is more corrsive to intestinal mucoss than inorganic
F! LESS corrosive
target organ of alkulmercury compounds (prganic)
brain
symptoms of organomercurial exposure
oral infestion (food chain)
NOTE: symptoms may not occur until weeks/months after acute exposure
neurological manifestations = ataxia, tremors, unsteady gait, illegible handwriting, slurred speech
sensory involvement = parethesias of lips, hands, feet and visual + hearing impairment
- emotional disturbances and erethism
- severe poisoning = may be irreversible
chemotherapeutic agent for acute promyelocytic leukemia
arsenic
forms of arsenic
trivalent = arsenites
pentavalent = arsenates
organic arsenic
either pentavalent or trivalent linked to a carbon
ASH3
gaseous hydride of As 3+
where is arsenic mainly stored
liver, kidney, <3, lung, etc.
where is the highest concentrations of arsenic found
hair and nails due to high sulfhydral content of kaeratin
arsenic is chemically similar to this
phosphorus so also deposited in bones and teeth
T or F. Arsenic readily causes placenta
T = fetal damage
arsenic half-life
10 hours
arsenobentaine
non-toxic
organic seafood arsenic
lobster
this uncouples ox phosphorylation by interfering in the formation of ATP
pentavalent arsenic
what does trivalent arsenic do?
- inhibit enzymes containing -SH groups
- inhibit pyruvate dehydrogenase resulting in inhibition of pyruvate ox and tricarboxylic acid cycle
- impaired gluconeogenesis and reduced ox phosphorylation
symptoms of acute arsenic exposure
diffuse skin rash
GI:
- extreme gastroenteritis bc of corrosion; burning esophageal pain, difficulty swallowing, unbearable stomach pain
- nausea, projectile vomiting, explosive diarrhea
- rice-water stools, bloody diarrhea and vomitus
excessive bleeding compromises circulatory system, BP drops = vascular shock and death
renal:
- tubular necrosis and renal failure
- urine outflow decreases and uremia may develop
delayed actions:
- ECG abnormalities (delayed cardiomyopathy)
- peripheral neuropathy = paresthesias, foot drop, wrist drop, slow reflexes
- liver cirrhosis
symptoms of chronic arsenic exposure
insidious non-specifc symptoms
- weakness, tiredness, lack of appetite, weight loss, irritability, garlic odor on breath
specific
- dark brown pigmentation and thickening of keratin layer
- nails thicken and Mee’s Lines develop = white bands across width of nail
peripheral neuropathies (LEGS > arms affected); paralysis of both motor and sensory pathways
ulcerations of GI
hepatic injury = hepatitis and cirrhosis
rapid and fatal hemolysiks is a unique characteris of this
arsine gas
- arsine combines with Hb = react w O2 => hemolysis
classic arsine triad
hemolysis
ab pain
hematuria
arsine gas: jaundice appears after ___ hours
24
copper skin pigmentaiton
arsine gas
due to methem???
high levels of arsine gas causes
direct multisystem cytotoxicity
one of heavy metals of greatest toxicological concern
cadmium
exposure of cadmium
electroplating
pigments
plastic stabilizers
batteries
also found in nature with lead and zinc (mining)
where does cadmium accumulate in the body
lung, liver, kidney
this is the heavy metal most prone to accumulate in the body
cadmium
what does cadmium do in the body
inhibits enymes containing sulfhydrul groups
- binds to other ligands on proteins and purines
inhibits alpha1-antitrypsin = pulmonary symptoms
competes w cellular uptake of various other metals in body such as copper and zinc
oral symptoms of cadmium toxicity
severe nausea, diarrhea, vomiting
muscular cramps
salivation
dizziness
proteinuria
glycosuria
osteomalacia
inhalation symptoms of cadmium
rhinorrhea
difficulty breathing
chest pain
pulmonary edema
progressive emphysema
azotemia (urea/other nitrogenous bodies in blood)
proteinuria
liver necrosis
I’tai-I’tai Byo
ouch-ouch disease
bone and muscle pain
what is ouch-ouch disease
severe cadmium poisoning
Toyama, Japan
rice fields
renal damage => disturbances in calcium and phosphorus metabolism = skeletal abnormalities, severe leg + back pain
