Creutzfeldt-Jakob disease pathophysiology: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
== | == Pathogenesis == | ||
* The | * The CJD prion promotes refolding of the native proteins into the diseased state. | ||
* The number of misfolded [[protein]] molecules increases exponentially, and the process leads to a large quantity of insoluble prions in the affected cells. | |||
* This mass of misfolded [[protein]]s 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. | |||
* The disease | ==Transmission== | ||
* The majority of cases of Creutzfeldt-Jakob disease are thought to be non-transmissible (sporadic form). | |||
* The defective protein associated with Creutzfeldt-Jakob disease can be inherited (familial form) or transmitted (iatrogenic form) through the following: | |||
** [[human growth hormone]] (hGH) products | |||
** [[cornea]]l grafts | |||
** Dural grafts or [[electrode]] implants<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> | |||
** usage of [[Human growth hormone|HGH]] drawn from the [[pituitary gland]]s of [[cadaver]]s<ref name="titleHGH Linked to Brain Eater">{{cite web |url=http://www.wired.com/news/medtech/0,1286,62998,00.html |title=HGH Linked to Brain Eater |accessdate=2007-12-02 |format= |work=}}</ref> | |||
** Consumption of infected animals | |||
** Cannibalism | |||
* The disease has also been shown to result from the [[cadaver|<nowiki/>]]s who died from Creutzfeldt-Jakob disease, 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 [[prion]] particles can also cause the development of classic CJD. | * 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 [[prion]] particles can also cause the development of classic CJD. | ||
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* [[Cannibalism]] has also been implicated as a transmission mechanism for abnormal [[prion]]s, causing the disease known as [[Kuru (disease)|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. | * [[Cannibalism]] has also been implicated as a transmission mechanism for abnormal [[prion]]s, causing the disease known as [[Kuru (disease)|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. | ||
* [[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. | * [[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. [[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=== | ===Mutations=== | ||
[[Mutations]] in the gene responsible for the production of prion protein can cause misfolding of the alpha helical regions into beta pleated sheets. | * [[Mutations]] in the gene responsible for the production of prion protein can cause misfolding of the alpha helical regions into beta pleated sheets. | ||
* This change in the conformation disables the ability of the protein to undergo digestion. | |||
* Individuals may also acquire CJD genetically through the [[mutation]] occurring [[PRNP|''PRNP'']] gene. | |||
=== | ===Gross Pathology=== | ||
* On gross pathology, the brain tissue appears "spongy" with areas of perforation within the brain tissue. | |||
=== Microscopic Pathology === | |||
* CJD is associated with the build-up of abnormal [[prion]] [[proteins]]. | |||
* The following microscopic findings may be present in CJD: | |||
** Spongiform changes | |||
** Neuronal loss | |||
** [[Astrocyte]] proliferation | |||
** Deposition of prion protein throughout the brain<ref name="Sellars-2002">{{Cite journal | last1 = Sellars | first1 = RJ. | last2 = Collie | first2 = DA. | last3 = Will | first3 = RJ. | title = Progress in understanding Creutzfeldt-Jakob disease. | journal = AJNR Am J Neuroradiol | volume = 23 | issue = 7 | pages = 1070-2 | month = Aug | year = 2002 | doi = | PMID = 12169459 }}</ref> | |||
[[Image:Spongiform changes in CJD.jpg|left|220px|Spongiform changes in brain in CJD]] | |||
Revision as of 19:53, 17 March 2016
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Creutzfeldt-Jakob disease is one of the transmissible spongiform encephalopathies (TSEs). The causative agents of TSEs are believed to be prions. The term "prions" refers to abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins that are found most abundantly in the brain. The functions of these normal prion proteins have still not been completely understood. The abnormal folding of the prion proteins leads to brain damage and the characteristic signs and symptoms of the disease. Prion diseases are usually rapidly progressive and always fatal.[1]
Pathophysiology
Pathogenesis
- The CJD prion promotes refolding of the native proteins into the diseased state.
- The number of misfolded protein molecules increases exponentially, and the process leads to a large quantity of insoluble prions in the 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.
Transmission
- The majority of cases of Creutzfeldt-Jakob disease are thought to be non-transmissible (sporadic form).
- The defective protein associated with Creutzfeldt-Jakob disease can be inherited (familial form) or transmitted (iatrogenic form) through the following:
- human growth hormone (hGH) products
- corneal grafts
- Dural grafts or electrode implants[2][3][4]
- usage of HGH drawn from the pituitary glands of cadavers[5]
- Consumption of infected animals
- Cannibalism
- The disease has also been shown to result from the s who died from Creutzfeldt-Jakob disease, 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 prion particles 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. Copper-hydrogen peroxide has been suggested as an alternative to the current recommendation of sodium hydroxide or sodium hypochlorite.[6] thermal depolymerization also destroys prions in infected organic and inorganic matter, since the process dissolves protein at the molecular level.
Mutations
- Mutations in the gene responsible for the production of prion protein can cause misfolding of the alpha helical regions into beta pleated sheets.
- This change in the conformation disables the ability of the protein to undergo digestion.
- Individuals may also acquire CJD genetically through the mutation occurring PRNP gene.
Gross Pathology
- On gross pathology, the brain tissue appears "spongy" with areas of perforation within the brain tissue.
Microscopic Pathology
- The following microscopic findings may be present in CJD:
- Spongiform changes
References
- ↑ "http://www.cdc.gov/ncidod/dvrd/prions/". Retrieved 16 February 2014. External link in
|title=(help) - ↑ "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.
- ↑ "HGH Linked to Brain Eater". Retrieved 2007-12-02.
- ↑ 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.
- ↑ Sellars, RJ.; Collie, DA.; Will, RJ. (2002). "Progress in understanding Creutzfeldt-Jakob disease". AJNR Am J Neuroradiol. 23 (7): 1070–2. PMID 12169459. Unknown parameter
|month=ignored (help)