Sandbox:josephine
Lead Poisoning
Historical perspective
The symptoms of Lead Poisoning were described in the book De Materia Medica ,the leading pharmacological text for centuries written by Dioscorides. [1]
outbreaks
Though Lead was known to exist for thousands of years its use surged in the 20 th century as it was found to reduce burning of fuel and decrease the “engine Knock”,due to its malleable nature it was used for transporting drinking water, soldering food cans, making paints durable and bright, and killing insects. About 80% of workers in Standard oil NJ ,manufacturing tetraethyl lead were found to have lead poisoning .The discovery of which lead to the ban of leaded gasoline in NY and NJ.[2]
Pathophysiology
Once Lead is absorbed it gets deposited in the bones(70% in adults and 95% in children).
Roughly 1% circulates in the blood,99% of which is in the RBC’s.[3]
Lead a divalent metal similar to calcium, iron and zinc uses channels like calcium channel or Divalent Metal Transporter(DMT) and enters the cells and acts as a cofactor to enzymes.
Pathology
Brain
Lead exposure in childhood is associated with decreased brain volume; this might be due to reduced neuronal size/dendritic arborisation and this reduced volume of brain persists into adulthood.[4]
Kidney
Lead exposure is a known risk factor for Chronic Kidney Disease(CKD)[5]
Nephrotoxic effects include
Intra nuclear inclusion bodies in Proximal Tubule cells
Tubulo interstitial fibrosis
It can cause decrease in Glomerular Filtration Rate(GFR).
CVS
Lead causes cellular changes that are characteristic for hypertension and atherosclerosis.
Laboratory studies revealed that chronic ,Low level lead exposure increases oxidative stress, decreases nitric oxide levels and induces vast spasm by activating protein kinase C there by causing hypertension.
By inactivation of nitric oxide, increased hydrogen peroxide levels, inhibition of endothelial repair, impairing angiogenesis, promoting thrombus formation causes atherosclerosis.[6]
Genetics
Lead a divalent metal similar to calcium, iron and zinc uses channels like calcium channel or Divalent Metal Transporter(DMT) and enters the cells and acts as a cofactor to enzymes.Hence genetic conditions that increase the levels of metals like iron ,calcium can make a person more susceptible for lead poisoning.[7]
Natural History,Complications,Prognosis
Studies conducted in the recent past have confirmed that long term exposure of low levels of lead, which were previously determined to be safe are a major risk factor for atherosclerotic cardiovascular disease in adults and cognitive deficits in children. The effects of exposure to lead on long term basis varies in children and adults.
Low level lead poisoning in children was found to be a risk factor for :
Preterm Labor
Cognitive defects
Attention Deficit Hyperkinetic Disorder(ADHD)
Elevated Blood Pressure
Reduced Heart rate variability.
In adults it is associated with :
CKD
Hypertension
Effects on Growth and Development
Lead exposure is found to be a risk factor for preterm birth ,a 10 microgram elevation in blood lead levels is associated with 70 % increase in preterm birth.For those with Vitamin D deficiency this risk is even more elevated.
Lead exposure is associated with reduced I.Q ,with higher reductions occurring at relatively low levels of exposure.[8]
Childhood exposure to Lead is a known risk factor for anti social disorders ,including
Conduct disorder
Delinquent behaviour
Criminal behaviour.
In Adults:
Higher blood or bone levels are found to be congruently associated with accelerated cognitive decline; especially in those withAPOE4 alleles, drawing suspicion that it may have a role as a risk factor for late onset Alzheimer’s disease.
Effects on CVS
Lead causes cellular changes that are characteristic for hypertension and atherosclerosis.Is is a leading risk factor for death from cardiovascular disease. Laboratory studies revealed endothelial cells incubated in lead for 72 hours at concentrations of 0.14 to 8.2 μg per liter showed signs of membrane damage , which is the earliest finding in the natural history of atherosclerosis.
Studies revealed that the risk of death from cardiovascular disease and coronary artery disease increased sharply at levels below 50 μg per liter, when adjusted for other risk factors.
Hypertension:
The incidence if hypertension in the U.S decreased tremendously during the phaseout of leaded gasoline.
The usual factors like smoking, antihypertensive medicines, obesity, or even the larger size of the cuff used to measure blood pressure in persons with obesity — did not explain the decline.but it was observed that the median blood lead levels dropped by 100 μg per litre over a period of 18 years, which point towards the role of Lead in the causation of hypertension.
- ↑ Hernberg S (September 2000). "Lead poisoning in a historical perspective". Am J Ind Med. 38 (3): 244–54. doi:10.1002/1097-0274(200009)38:3<244::aid-ajim3>3.0.co;2-f. PMID 10940962.
- ↑ Rosner D, Markowitz G (April 1985). "A 'gift of God'?: The public health controversy over leaded gasoline during the 1920s". Am J Public Health. 75 (4): 344–52. doi:10.2105/ajph.75.4.344. PMC 1646253. PMID 2579591.
- ↑ Barry PS (May 1975). "A comparison of concentrations of lead in human tissues". Br J Ind Med. 32 (2): 119–39. doi:10.1136/oem.32.2.119. PMC 1008038. PMID 1131339.
- ↑ Cecil KM, Brubaker CJ, Adler CM, Dietrich KN, Altaye M, Egelhoff JC, Wessel S, Elangovan I, Hornung R, Jarvis K, Lanphear BP (May 2008). "Decreased brain volume in adults with childhood lead exposure". PLoS Med. 5 (5): e112. doi:10.1371/journal.pmed.0050112. PMID 18507499.
- ↑ Batuman V, Landy E, Maesaka JK, Wedeen RP (July 1983). "Contribution of lead to hypertension with renal impairment". N Engl J Med. 309 (1): 17–21. doi:10.1056/NEJM198307073090104. PMID 6406892.
- ↑ Vaziri ND (August 2008). "Mechanisms of lead-induced hypertension and cardiovascular disease". Am J Physiol Heart Circ Physiol. 295 (2): H454–65. doi:10.1152/ajpheart.00158.2008. PMC 2519216. PMID 18567711.
- ↑ Kayaaltı Z, Akyüzlü DK, Söylemezoğlu T (February 2015). "Evaluation of the effect of divalent metal transporter 1 gene polymorphism on blood iron, lead and cadmium levels". Environ Res. 137: 8–13. doi:10.1016/j.envres.2014.11.008. PMID 25483413.
- ↑ Canfield RL, Henderson CR, Cory-Slechta DA, Cox C, Jusko TA, Lanphear BP (April 2003). "Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter". N Engl J Med. 348 (16): 1517–26. doi:10.1056/NEJMoa022848. PMC 4046839. PMID 12700371.