Sources:
Some sources of lead include:
-Old paints
-Batteries
-Leaded Fuel
-Old toys made in China
-Glaze finish on ceramics
-Fishing weights/sinkers
-Bullets
Toxicokinetics:
Typically ingested orally into the GI tract by children due to eating or chewing on items containing lead. Absorption amounts depend on how full the stomach is (i.e. empty vs. full).
It also depends on any mineral deficiencies of: zinc, calcium, or iron.
Distribution of lead typically to soft tissue in the liver and kidneys.
Lead in the blood is found in erythrocytes bound to hemoglobin. About half of the lead found in the blood is due to lead being released from the bone.
Excretion primarily through the kidneys into urine.
*Lead is able to cross through the placenta to the fetal tissue.
Carcinogenicity:
Recently inorganic lead has been classified as potentially linked to cancer in humans.
Organic lead compounds do not seem to be carcinogenic.
Mechanism of action:
Lead primarily causes anemia by inhibiting ALAD and ferrochelatase. ALAD is a catalyst condensing ALA into Phorophobilinogen (PBG). Ferrochelatase is a catalyst inserting iron into protopophyrin rings to produce heme.
Target Organs:
The Central Nervous System (CNS) and blood
Signs and Symptoms of Toxicity:
*Symptoms vary by age group
Newborns:
-Premature birth, Slowed growth, Low weight at birth
Children:
-Seizures, Vomiting, Constipation, Hearing Loss, Delays in Development, Learning Disabilities, Appetite loss, Weight loss, Abdominal pain, Loss of hearing, Abdominal Pain, Pica.
Adults:
-High BP, Joint and muscle pain, abdominal pain, mood disorders, constipation, confusion, headache. Women-miscarriage, still born, premature delivery of baby. Men- Abnormal sperm or sperm count.
Treatments:
Basic treatment is removal of lead source. Reducing exposure can reduce levels of lead in the blood.
Severe cases treatment is chelation therapy (children) and EDTA chelation therapy (adults).
Genetic Susceptibility or Heritable Traits:
Small differences in DNA sequencing of ALAD and VDR genes could impact how lead is handled in the body. ALAD has two alleles (ALAD1 and ALAD2) that have already been observed to have an impact on the pharmacokinetics of lead. However, recently there have been observations of two VDR alleles (VDRb and VDRB) impacting pharmacokinetics of lead.
Biomarkers of lead:
Primarily found in urine levels and blood levels. Below are the different blood and urine biomarkers.
Historical or Unique Exposures:
Lead exposure is unavoidable considering lead is found in earths very own atmosphere. However, the most notable exposures have been from lead house paint. Children used to suffer from lead poisoning and exposure in houses with old lead paint chips or dust containing lead paint. This exposure resulted because of hand-to-mouth contact.
Essentiality and Deficiency:
As stated above, lead poisoning can be increased significantly by different mineral deficiencies. However, lead deficiency has very minimal affects.