Lead toxicity: Difference between revisions

Revision as of 03:52, 16 December 2014

Stable metallic element (no. 82)
Incredible environmental burden secondary to inclusion in paints, fuels, and industrial uses
Average blood levels in US have fallen from 12.8 mcg/dL in the late 1970's to 2mcg/dL

Interferes with the action of divalent cations and sulfhydryl groups
- Particularly toxic to Zinc containing enzymes
- Binds to calcium activated enzymes with 10,000x great affinity that calcium
Directly toxic to renal tubules

Rapidly and completely absorbed from lungs
Variable GI absorption
- Children absorb more than adults (70% vs. 20%)
- Affected by nutritional status, calcium stores and iron stores

Excreted in urine and stool
Amount excreted varies with age
- Children retain about 70% while adults only retain about 1%

Lead paint
Occupational
Soil contamination
Water
Food
Alternative/herbal medications
Poorly monitored imported products
- Eg. Toys imported from China which were coated in lead paints

CNS symptoms predominate
Lethargy, fatigue, headache, irritability, memory loss, tremor
Severe symptoms: AMS, coma, seizures, cerebral edema
PNS toxicity
- Causes segmental demyelination
- Peripheral neuropathy
  - Upper >> Lower extremities
  - Extensors >> Flexors

Highest body levels found in proximal tubules after acute exposure
- Results in proteinuria, particularly β 2-microglobulin and N-acetylglucosidase.

Basophilic stippling
- From precipitation of nuclear contents
Inhibitor of heme synthesis
- Can lead to either a normochromic or hypochromic anemia

Can cause placenta
- Because lead is stored in bones and there is higher bone turnover during pregnancy, women with previous lead toxicity can have lead intoxicated children despite mother being asymptomatic.
Higher rate of stillbirths and spontaneous abortion
Decreased sperm counts

Encephalopathy appears at lower levels
Symptoms: Irritability, apathy, fatigue, obtundation
Severe symptoms: Cerebral edema, seizures
Can lead to permanent changes in brain architecture
- Inhibits enzymes that mediate arborization of synapses and neuronal cellular adhesion molecules
  - Hippcampus thought to be primary sight of action secondary to high zinc levels
Disturbs blood brain barrier permeability which can be chronic
Long term sequelae
- Cognitive disturbances (from slight learning disability to profound mental retardation)
  - Loss of 5 IQ points per 10μg/dL elevation
- Hyperactivity, aggression and antisocial behaviors
Peripheral neuropathy similar to adults

Chelation:
- Treat children with acute blood Lead levels >45ug/dL or chronic >70ug/dL
- Consider treating symptomatic adults with Lead >50ug/dL or asymptomatic >70ug/dL
Penicillamine and Succimer
- Oral medications
- Only used in children
- Succimer has not been studied for Lead levels >60ug/dL
- Penicillamine: second-line agent, requires B6 supplementation
IV/IM EDTA (edetate calcium disodium)
- do not use as sole agent if encephalopathy present (does not cross blood-brain barrier)
- Must have given BAL for at least 4h if Lead >100ug/dL
IM BAL (dimercaprol)
- First line agent if encephalopathy present
- excreted in bile, can use in renal failure

Authors:

@@ Line 103: / Line 103: @@
 ==Treatment==
-*Chelation
+*Chelation:
-**EDTA
+**Treat children with acute blood Lead levels >45ug/dL or chronic >70ug/dL
-**BAL
+**Consider treating symptomatic adults with Lead >50ug/dL or asymptomatic >70ug/dL
+*Penicillamine and Succimer
+**Oral medications
+**Only used in children
+**Succimer has not been studied for Lead levels >60ug/dL
+**Penicillamine: second-line agent, requires B6 supplementation
+*IV/IM EDTA (edetate calcium disodium)
+**do not use as sole agent if encephalopathy present (does not cross blood-brain barrier)
+**Must have given BAL for at least 4h if Lead >100ug/dL
+*IM BAL (dimercaprol)
+**First line agent if encephalopathy present
+**excreted in bile, can use in renal failure
 ==See Also==