RH 15

DAY1
-Lead
cause
-Lead
than

toxicity most commonly occurs via ingestion; houses build before 1950 can
exposure to lead.
exposure can affect gross motor function; lead is more harmful to children
adults because it can affect the developing nerves and brain. The younger
the child, the more harmful lead can be. Unborn children are the most vu
lnerable. Possible problems: behavior/attention problems, failure at school,
hearing problems, kidney damage, reduced IQ, slowed body growth. Very hi
gh levels of lead may cause vomiting, staggering walk (abnormal gait), muscle
weakness, seizures, or coma. Inhibition of synaptogenesis may explain co
gnitive problems. Cholinergic, dopaminergic, and glutamergic neurons are affecte
d
in that order.
-5micrograms/mL causes developmental toxicity which includes: decreased IQ, decr
eased hearing, decreased growth, impaired peripheral nerve function, and fetal
effects by transplacental transfer. 10micrograms/mL is needed in mom to
tranfer to fetus.
-100micrograms/mL causes encephalopathy, and 150micrograms/mL is fatal.
-Most circulating lead is bound to red blood cells with only a small fraction in
the plasma. Most lead is excreted in the urine. The process is slow, so it requ
ires
long term exposure to reach clinical toxicity such as months to years. B
one is a major storage unit for lead, containing the vast majority of the body l
ead
burden (>90%). Lead can stay in the bone for decades, releasing a contin
uous amount of lead into the the tissues and blood, even after exposure has ceas
ed
and chelation therapy has been given.
-Lead inhibits several calcium and zinc dependent processes. It interferes with
mitochondrial function in vitro by interfering with calcium uptake. Protein Kina
se C
is a calcium-dependent enzyme critical to brain function, and its inhibi
tion by lead may contribute to neurotoxicity.
-Lead also inhibits ALA dehydratase (cytoplasm) and Ferrochelatase (mitochondria
), leading to the buildup of ALA and protoporhyrin.
-Peripheral blood smear-->basophilic stippling of RBC's, the blue granules are r
ibosomes. Hypochromic, microcytic anemia, low cell count.
-Chelation therapy consists of EDTA with Ca++ and Na+ with dimercaprol (dimercap
rol can cross the blood brain barrier)
-The half life of lead in blood is 36 days, in soft tissue it is 40 days, and in
bone it is 10-30 years.
-Blood Lead Level (BLL) test is the best test for lead poisoning, but erythrocyt
e protoporphyrin (EP) assay is also ok. These tests do not measure the total bod
y
burden. They are just reflective of recent or ongoing exposure.
-Methylmercury: accumulates in fish, absorbed in our GI, complexed with free cys
teine and acts as methionine in the body. Can cross the blood brain barrier!
DAY2
-Dimercaprol crosses the BBB, and has SH groups it uses to bind to lead.
-GFR is calculated using the Shwartz equation: (k x L)/(serum creatinine concent
ration)
-If mom supplements with Ca++ it reduces lead transmission to baby.
-If blood lead level is present, but low, and source of exposure is gone, you ca
n treat with succimer (DMSA).