Lead poisoning pathophysiology: Difference between revisions
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{{Lead poisoning}} | {{Lead poisoning}} | ||
{{CMG}}; {{AE}} | {{CMG}}; {{AE}}{{AKS}} | ||
==Overview== | ==Overview== | ||
'''[[Lead]] poisoning''' is a medical condition, also known as '''saturnism''', '''plumbism''', or '''painter's colic''' caused by increased blood lead levels. Lead may cause irreversible neurological damage as well as [[renal disease]], cardiovascular effects, and reproductive toxicity. Humans have been mining and using this heavy metal for thousands of years, poisoning themselves in the process due to accumulation and exposure. These dangers have long been known, though the modern understanding of their full extent and the small amount of [[lead]] necessary to produce them is relatively recent; blood lead levels once considered safe are now considered hazardous, with no known threshold. Reducing these hazards requires both individual actions and public policy regulations. <ref> [www.atsdr.cdc.com]</ref> | |||
==Pathophysiology== | ==Pathophysiology== | ||
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===Pathogenesis=== | ===Pathogenesis=== | ||
Lead has no known physiologically relevant role in the body. The toxicity of lead comes from its ability to mimic other biologically important [[metal]]s, most notably [[calcium]], [[iron]] and [[zinc]] which act as [[cofactor]]s in many enzymatic reactions. | *Lead has no known physiologically relevant role in the body. | ||
*The toxicity of lead comes from its ability to mimic other biologically important [[metal]]s, most notably [[calcium]], [[iron]] and [[zinc]] which act as [[cofactor]]s in many enzymatic reactions. | |||
*Following ingestion, lead is able to bind to and interact with many of the same [[enzymes]] as these are metals, but due to its differing chemistry, does not properly function as a co-factor, thus interfering with the enzyme's ability to catalyze its normal reaction(s). | |||
*[[Lead toxicity]] symptoms arise are thought to occur by interfering with an essential enzyme [[delta-AminoLevulinic Acid Dehydratase]], or ALAD. ALAD is a zinc-binding protein which is important in the biosynthesis of [[heme]], the co-factor found in [[hemoglobin]]. Lead poisoning also inhibits the enzyme [[ferrochelatase]] which catalyzes the joining of [[protoporphyrin IX]] and [[Fe]]2+ to form [[Heme]]. <ref name="pmid11032836">{{cite journal| author=Jaffe EK, Martins J, Li J, Kervinen J, Dunbrack RL| title=The molecular mechanism of lead inhibition of human porphobilinogen synthase. | journal=J Biol Chem | year= 2001 | volume= 276 | issue= 2 | pages= 1531-7 | pmid=11032836 | doi=10.1074/jbc.M007663200 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11032836 }} </ref> <ref name="pmid17366816.">{{cite journal| author=Scinicariello F, Murray HE, Moffett DB, Abadin HG, Sexton MJ, Fowler BA| title=Lead and delta-aminolevulinic acid dehydratase polymorphism: where does it lead? A meta-analysis. | journal=Environ Health Perspect | year= 2007 | volume= 115 | issue= 1 | pages= 35-41 | pmid=17366816. | doi= | pmc=1797830 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17366816 }} </ref> | |||
== | ===Genetics=== | ||
*So far three [[polymorphic genes]] have been identified to be able to potentially influence the [[bioaccumulation]] and [[toxicokinetics]] of [[lead]] in humans. These genes are [[delta-aminolevulinic acid dehydratase (ALAD) gene]], the [[hemochromatosis gene]] and the [[vitamin D receptor]] [[(VDR)]]. Their relation to susceptibility especially to lead nephrotoxicity in high lead-exposed workers has been established. <ref name="pmid19548578">{{cite journal| author=Wang A, Wang Q, Song Q, Xu J| title=[Study of ALAD and VDR gene polymorphisms associated with lead nephrotoxicity susceptibility]. | journal=Wei Sheng Yan Jiu | year= 2009 | volume= 38 | issue= 3 | pages= 326-9 | pmid=19548578 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19548578 }} </ref> <ref name="pmid15209014">{{cite journal| author=Wu S, Yan C, Shen X| title=[Molecular genetic susceptibility to lead poisoning]. | journal=Wei Sheng Yan Jiu | year= 2004 | volume= 33 | issue= 2 | pages= 226-8, 232 | pmid=15209014 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15209014 }} </ref> | |||
* | |||
*[[Delta -aminolevulinic acid dehydratase]] [[(ALAD)]] plays an important role in [[lead poisoning]], and [[polymorphisms]] in the [[ALAD gene]] might affect the symptoms the individual patients experience. <ref name="pmid19028776">{{cite journal| author=Shaik AP, Jamil K| title=A study on the ALAD gene polymorphisms associated with lead exposure. | journal=Toxicol Ind Health | year= 2008 | volume= 24 | issue= 7 | pages= 501-6 | pmid=19028776 | doi=10.1177/0748233708095770 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19028776 }} </ref> | |||
* | |||
==References== | ==References== | ||
Latest revision as of 15:11, 15 August 2018
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aksiniya Stevasarova, M.D.
Overview
Lead poisoning is a medical condition, also known as saturnism, plumbism, or painter's colic caused by increased blood lead levels. Lead may cause irreversible neurological damage as well as renal disease, cardiovascular effects, and reproductive toxicity. Humans have been mining and using this heavy metal for thousands of years, poisoning themselves in the process due to accumulation and exposure. These dangers have long been known, though the modern understanding of their full extent and the small amount of lead necessary to produce them is relatively recent; blood lead levels once considered safe are now considered hazardous, with no known threshold. Reducing these hazards requires both individual actions and public policy regulations. [1]
Pathophysiology
Pathogenesis
- Lead has no known physiologically relevant role in the body.
- The toxicity of lead comes from its ability to mimic other biologically important metals, most notably calcium, iron and zinc which act as cofactors in many enzymatic reactions.
- Following ingestion, lead is able to bind to and interact with many of the same enzymes as these are metals, but due to its differing chemistry, does not properly function as a co-factor, thus interfering with the enzyme's ability to catalyze its normal reaction(s).
- Lead toxicity symptoms arise are thought to occur by interfering with an essential enzyme delta-AminoLevulinic Acid Dehydratase, or ALAD. ALAD is a zinc-binding protein which is important in the biosynthesis of heme, the co-factor found in hemoglobin. Lead poisoning also inhibits the enzyme ferrochelatase which catalyzes the joining of protoporphyrin IX and Fe2+ to form Heme. [2] [3]
Genetics
- So far three polymorphic genes have been identified to be able to potentially influence the bioaccumulation and toxicokinetics of lead in humans. These genes are delta-aminolevulinic acid dehydratase (ALAD) gene, the hemochromatosis gene and the vitamin D receptor (VDR). Their relation to susceptibility especially to lead nephrotoxicity in high lead-exposed workers has been established. [4] [5]
- Delta -aminolevulinic acid dehydratase (ALAD) plays an important role in lead poisoning, and polymorphisms in the ALAD gene might affect the symptoms the individual patients experience. [6]
References
- ↑ [www.atsdr.cdc.com]
- ↑ Jaffe EK, Martins J, Li J, Kervinen J, Dunbrack RL (2001). "The molecular mechanism of lead inhibition of human porphobilinogen synthase". J Biol Chem. 276 (2): 1531–7. doi:10.1074/jbc.M007663200. PMID 11032836.
- ↑ Scinicariello F, Murray HE, Moffett DB, Abadin HG, Sexton MJ, Fowler BA (2007). "Lead and delta-aminolevulinic acid dehydratase polymorphism: where does it lead? A meta-analysis". Environ Health Perspect. 115 (1): 35–41. PMC 1797830. PMID 17366816. Check
|pmid=value (help). - ↑ Wang A, Wang Q, Song Q, Xu J (2009). "[Study of ALAD and VDR gene polymorphisms associated with lead nephrotoxicity susceptibility]". Wei Sheng Yan Jiu. 38 (3): 326–9. PMID 19548578.
- ↑ Wu S, Yan C, Shen X (2004). "[Molecular genetic susceptibility to lead poisoning]". Wei Sheng Yan Jiu. 33 (2): 226–8, 232. PMID 15209014.
- ↑ Shaik AP, Jamil K (2008). "A study on the ALAD gene polymorphisms associated with lead exposure". Toxicol Ind Health. 24 (7): 501–6. doi:10.1177/0748233708095770. PMID 19028776.