Creutzfeldt-Jakob disease pathophysiology: Difference between revisions
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[[Prion]]s, the [[infectious agent]] of CJD, may not be inactivated by means of routine [[surgical instrument]] [[Autoclave|sterilization]] procedures. The [[World Health Organization]] and the US [[Centers for Disease Control and Prevention]] recommend that heat and chemical decontamination be used in combination to process instruments that come in contact with high-infectivity tissues. No cases of [[iatrogenic]] transmission of CJD have been reported subsequent to the adoption of current sterilization procedures, or since 1976.<ref>{{cite web|title =Questions and Answers: Creutzfeldt-Jakob Disease Infection-Control Practices|work =Infection Control Practices/CJD (Creutzfeldt-Jakob Disease, Classic)|publisher =Centers for Disease Control and Prevention|date =[[January 4]][[2007]]|url = http://www.cdc.gov/ncidod/dvrd/cjd/qa_cjd_infection_control.htm#sterilization|accessdate = 2007-06-09}}</ref><ref>{{cite web|title =WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies|Publisher =World Health Organization: Communicable Disease Surveillance and Control|date =[[26 March]] [[1999]]|url =http://www.who.int/csr/resources/publications/bse/WHO_CDS_CSR_APH_2000_3/en/|accessdate = 2007-06-09}}</ref><ref>{{cite journal |author=McDonnell G, Burke P. | title=The challenge of prion decontamination | journal=Clin Infect Dis | year=2003 | volume=36 | pages=1152–4 }}</ref>[[Copper]]-[[hydrogen peroxide]] has been suggested as an alternative to the current recommendation of [[sodium hydroxide]] or [[sodium hypochlorite]].<ref>{{cite journal | author=Solassol J, Pastore M, Crozet C, ''et al.'' | title=A novel copper-hydrogen peroxide formulation for prion decontamination | journal=J Infect Dis | year=2006 | volume=194 | pages=865–869 }}</ref> [[Thermal depolymerization]] also destroys [[prion]]s in infected organic and inorganic matter, since the process dissolves protein at the molecular level. | [[Prion]]s, the [[infectious agent]] of CJD, may not be inactivated by means of routine [[surgical instrument]] [[Autoclave|sterilization]] procedures. The [[World Health Organization]] and the US [[Centers for Disease Control and Prevention]] recommend that heat and chemical decontamination be used in combination to process instruments that come in contact with high-infectivity tissues. No cases of [[iatrogenic]] transmission of CJD have been reported subsequent to the adoption of current sterilization procedures, or since 1976.<ref>{{cite web|title =Questions and Answers: Creutzfeldt-Jakob Disease Infection-Control Practices|work =Infection Control Practices/CJD (Creutzfeldt-Jakob Disease, Classic)|publisher =Centers for Disease Control and Prevention|date =[[January 4]][[2007]]|url = http://www.cdc.gov/ncidod/dvrd/cjd/qa_cjd_infection_control.htm#sterilization|accessdate = 2007-06-09}}</ref><ref>{{cite web|title =WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies|Publisher =World Health Organization: Communicable Disease Surveillance and Control|date =[[26 March]] [[1999]]|url =http://www.who.int/csr/resources/publications/bse/WHO_CDS_CSR_APH_2000_3/en/|accessdate = 2007-06-09}}</ref><ref>{{cite journal |author=McDonnell G, Burke P. | title=The challenge of prion decontamination | journal=Clin Infect Dis | year=2003 | volume=36 | pages=1152–4 }}</ref>[[Copper]]-[[hydrogen peroxide]] has been suggested as an alternative to the current recommendation of [[sodium hydroxide]] or [[sodium hypochlorite]].<ref>{{cite journal | author=Solassol J, Pastore M, Crozet C, ''et al.'' | title=A novel copper-hydrogen peroxide formulation for prion decontamination | journal=J Infect Dis | year=2006 | volume=194 | pages=865–869 }}</ref> [[Thermal depolymerization]] also destroys [[prion]]s in infected organic and inorganic matter, since the process dissolves protein at the molecular level. | ||
===Mutations=== | |||
The CJD prion is dangerous because it promotes [[Protein folding|refolding]] of native proteins into the diseased state. The number of misfolded protein molecules will [[exponential growth|increase exponentially]], and the process leads to a large quantity of insoluble prions in affected [[cell (biology)|cells]]. This mass of misfolded proteins disrupts cell function and causes cell death. Mutations in the gene for the prion protein can cause a misfolding of the dominantly alpha helical regions into beta pleated sheets. This change in conformation disables the ability of the protein to undergo digestion. Once the prion is transmitted, the defective proteins invade the brain and are produced in a self-sustaining [[feedback loop]], causing exponential spread of the prion, death within a few months, although a few patients have been known to live as long as two years. | |||
===Microscopic Pathology=== | ===Microscopic Pathology=== | ||
The symptoms of CJD are caused by the progressive [[cell death|death]] of the brain's [[neuron|nerve cells]], which is associated with the build-up of abnormal [[prion]] [[proteins]]. When brain tissue from a CJD patient is examined under a [[microscope]], many tiny holes can be seen where whole areas of nerve cells have died. The word 'spongiform' in '[[transmissible spongiform encephalopathies]]' refers to the 'spongy' appearance of the [[brain]] tissue. | The symptoms of CJD are caused by the progressive [[cell death|death]] of the brain's [[neuron|nerve cells]], which is associated with the build-up of abnormal [[prion]] [[proteins]]. When brain tissue from a CJD patient is examined under a [[microscope]], many tiny holes can be seen where whole areas of nerve cells have died. The word 'spongiform' in '[[transmissible spongiform encephalopathies]]' refers to the 'spongy' appearance of the [[brain]] tissue. | ||
Revision as of 16:55, 26 December 2012
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Pathophysiology
The CJD prion is dangerous because it promotes refolding of native proteins into the diseased state. The number of misfolded protein molecules will increase exponentially, and the process leads to a large quantity of insoluble prions in affected cells. This mass of misfolded proteins disrupts cell function and causes cell death. Once the prion is transmitted, the defective proteins invade the brain and are produced in a self-sustaining feedback loop, causing exponential spread of the prion, death within a few months, although a few patients have been known to live as long as two years.
The defective protein can be transmitted by human growth hormone (hGH) products, corneal grafts, dural grafts or electrode implants (acquired or iatrogenic form: iCJD); it can be inherited (hereditary or familial form: fCJD); or it may appear for the first time in the patient (sporadic form: sCJD). In the hereditary form, a mutation occurs in the gene for PrP, PRNP. 10 to 15% of CJD cases are inherited. (CDC)
The disease has also been shown to result from usage of HGH drawn from the pituitary glands of cadavers who died from Creutzfeldt-Jakob Disease,[1] though the known incidence of this cause is (as of April 2004) quite small. The risk of infection through cadaveric HGH usage in the US only ceased when the medication was withdrawn in 1985.
It is thought that humans can contract the disease by consuming material from animals infected with the bovine form of the disease. The only suspected cases to arise thus far have been vCJD, although there are fears; based on animal studies — that consuming beef or beef products containing prionparticles can also cause the development of classic CJD.
Cannibalism has also been implicated as a transmission mechanism for abnormal prions, causing the disease known as kuru, found primarily among women and children of the Fore tribe in Papua New Guinea. While the men of the tribe ate the body of the deceased and were not affected, the women and children ate the brain and contracted the disease from infected brain tissue.
Prions, the infectious agent of CJD, may not be inactivated by means of routine surgical instrument sterilization procedures. The World Health Organization and the US Centers for Disease Control and Prevention recommend that heat and chemical decontamination be used in combination to process instruments that come in contact with high-infectivity tissues. No cases of iatrogenic transmission of CJD have been reported subsequent to the adoption of current sterilization procedures, or since 1976.[2][3][4]Copper-hydrogen peroxide has been suggested as an alternative to the current recommendation of sodium hydroxide or sodium hypochlorite.[5] Thermal depolymerization also destroys prions in infected organic and inorganic matter, since the process dissolves protein at the molecular level.
Mutations
The CJD prion is dangerous because it promotes refolding of native proteins into the diseased state. The number of misfolded protein molecules will increase exponentially, and the process leads to a large quantity of insoluble prions in affected cells. This mass of misfolded proteins disrupts cell function and causes cell death. Mutations in the gene for the prion protein can cause a misfolding of the dominantly alpha helical regions into beta pleated sheets. This change in conformation disables the ability of the protein to undergo digestion. Once the prion is transmitted, the defective proteins invade the brain and are produced in a self-sustaining feedback loop, causing exponential spread of the prion, death within a few months, although a few patients have been known to live as long as two years.
Microscopic Pathology
The symptoms of CJD are caused by the progressive death of the brain's nerve cells, which is associated with the build-up of abnormal prion proteins. When brain tissue from a CJD patient is examined under a microscope, many tiny holes can be seen where whole areas of nerve cells have died. The word 'spongiform' in 'transmissible spongiform encephalopathies' refers to the 'spongy' appearance of the brain tissue.
References
- ↑ "HGH Linked to Brain Eater". Retrieved 2007-12-02.
- ↑ "Questions and Answers: Creutzfeldt-Jakob Disease Infection-Control Practices". Infection Control Practices/CJD (Creutzfeldt-Jakob Disease, Classic). Centers for Disease Control and Prevention. January 42007. Retrieved 2007-06-09. Check date values in:
|date=(help) - ↑ "WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies". 26 March 1999. Retrieved 2007-06-09. Unknown parameter
|Publisher=ignored (|publisher=suggested) (help); Check date values in:|date=(help) - ↑ McDonnell G, Burke P. (2003). "The challenge of prion decontamination". Clin Infect Dis. 36: 1152&ndash, 4.
- ↑ Solassol J, Pastore M, Crozet C; et al. (2006). "A novel copper-hydrogen peroxide formulation for prion decontamination". J Infect Dis. 194: 865&ndash, 869.