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Do not fill this in! == Pathogenesis == [[File:Carswell-Tubercle.jpg|thumb|upright|[[Robert Carswell (pathologist)|Robert Carswell]]'s illustration of tubercle<ref name="GoodCooper1835">{{cite book| vauthors = Good JM, Cooper S, Doane AS |title=The Study of Medicine|url=https://books.google.com/books?id=K906AQAAMAAJ&pg=PA32|year=1835|publisher=Harper|page=32|url-status=live|archive-url=https://web.archive.org/web/20160810194616/https://books.google.com/books?id=K906AQAAMAAJ&pg=PA32|archive-date=10 August 2016}}</ref>]] About 90% of those infected with ''M. tuberculosis'' have [[asymptomatic]], latent TB infections (sometimes called LTBI),<ref name=Book90>{{cite book| vauthors = Skolnik R |title=Global health 101|year=2011|publisher=Jones & Bartlett Learning|location=Burlington, MA|isbn=978-0-7637-9751-5|page=[https://archive.org/details/globalhealth1010000skol/page/253 253]|url=https://archive.org/details/globalhealth1010000skol|url-access=registration|edition=2nd}}</ref> with only a 10% lifetime chance that the latent infection will progress to overt, active tuberculous disease.<ref name=Arch2009>{{cite book | vauthors = Mainous III AR, Pomeroy C |title=Management of antimicrobials in infectious diseases: impact of antibiotic resistance|year=2009|publisher=Humana Press|location=Totowa, NJ|isbn=978-1-60327-238-4|page=74|url=https://books.google.com/books?id=hwVFAPLYznsC&pg=PA74|edition=2nd rev.|url-status=live|archive-url=https://web.archive.org/web/20150906224212/https://books.google.com/books?id=hwVFAPLYznsC&pg=PA74|archive-date=6 September 2015}}</ref> In those with HIV, the risk of developing active TB increases to nearly 10% a year.<ref name=Arch2009/> If effective treatment is not given, the death rate for active TB cases is up to 66%.<ref name=WHO2012data>{{cite web|url=https://www.who.int/mediacentre/factsheets/fs104/en/index.html|title=Tuberculosis Fact sheet NΒ°104|publisher=[[World Health Organization]] (WHO)|date=November 2010|access-date=26 July 2011|url-status=live|archive-url=https://web.archive.org/web/20061004013508/http://www.who.int/mediacentre/factsheets/fs104/en/index.html|archive-date=4 October 2006}}</ref> [[File:Tuberculous epididymitis Low Power.jpg|thumb|Microscopy of tuberculous epididymitis. [[H&E]] stain]] TB infection begins when the mycobacteria reach the [[Pulmonary alveolus|alveolar air sacs]] of the lungs, where they invade and replicate within [[endosomes]] of alveolar [[macrophages]].<ref name=Robbins/><ref name=Houben>{{cite journal | vauthors = Houben EN, Nguyen L, Pieters J | title = Interaction of pathogenic mycobacteria with the host immune system | journal = Current Opinion in Microbiology | volume = 9 | issue = 1 | pages = 76β85 | date = February 2006 | pmid = 16406837 | doi = 10.1016/j.mib.2005.12.014 }}</ref><ref>{{cite journal | vauthors = Queval CJ, Brosch R, Simeone R | title = Mycobacterium tuberculosis | journal = Frontiers in Microbiology | volume = 8 | page= 2284 | year = 2017 | pmid = 29218036 | pmc = 5703847 | doi = 10.3389/fmicb.2017.02284 | doi-access = free }}</ref> Macrophages identify the bacterium as foreign and attempt to eliminate it by [[phagocytosis]]. During this process, the bacterium is enveloped by the macrophage and stored temporarily in a membrane-bound vesicle called a phagosome. The phagosome then combines with a lysosome to create a phagolysosome. In the phagolysosome, the cell attempts to use [[reactive oxygen species]] and acid to kill the bacterium. However, ''M. tuberculosis'' has a thick, waxy [[mycolic acid]] capsule that protects it from these toxic substances. ''M. tuberculosis'' is able to reproduce inside the macrophage and will eventually kill the immune cell. The primary site of infection in the lungs, known as the [[Ghon focus]], is generally located in either the upper part of the lower lobe, or the lower part of the [[lung|upper lobe]].<ref name=Robbins/> Tuberculosis of the lungs may also occur via infection from the blood stream. This is known as a [[Simon focus]] and is typically found in the top of the lung.<ref>{{cite book| vauthors = Khan MR |title=Essence of Paediatrics|year=2011|publisher=Elsevier India|isbn=978-81-312-2804-3|page=401|url=https://books.google.com/books?id=gERCc6KTxwoC&pg=PA401|url-status=live|archive-url=https://web.archive.org/web/20150906193259/https://books.google.com/books?id=gERCc6KTxwoC&pg=PA401|archive-date=6 September 2015}}</ref> This hematogenous transmission can also spread infection to more distant sites, such as peripheral lymph nodes, the kidneys, the brain, and the bones.<ref name=Robbins/><ref name=Herrmann_2005>{{cite journal | vauthors = Herrmann JL, Lagrange PH | title = Dendritic cells and Mycobacterium tuberculosis: which is the Trojan horse? | journal = Pathologie-Biologie | volume = 53 | issue = 1 | pages = 35β40 | date = February 2005 | pmid = 15620608 | doi = 10.1016/j.patbio.2004.01.004 }}</ref> All parts of the body can be affected by the disease, though for unknown reasons it rarely affects the [[heart]], [[skeletal muscle]]s, [[pancreas]], or [[thyroid]].<ref>{{cite journal | vauthors = Agarwal R, Malhotra P, Awasthi A, Kakkar N, Gupta D | title = Tuberculous dilated cardiomyopathy: an under-recognized entity? | journal = BMC Infectious Diseases | volume = 5 | issue = 1 | pages = 29 | date = April 2005 | pmid = 15857515 | pmc = 1090580 | doi = 10.1186/1471-2334-5-29 | doi-access = free }}</ref> Tuberculosis is classified as one of the [[granuloma]]tous inflammatory diseases. [[Macrophage]]s, [[epithelioid cell]]s, [[T cell|T lymphocytes]], [[B cell|B lymphocytes]], and [[fibroblast]]s <!-- are among the cells that --> aggregate to form granulomas, with [[lymphocytes]] surrounding the infected macrophages. When other macrophages attack the infected macrophage, they fuse together to form a giant multinucleated cell in the alveolar lumen. The granuloma may prevent dissemination of the mycobacteria and provide a local environment for interaction of cells of the immune system.<ref name=Grosset /> However, more recent evidence suggests that the bacteria use the granulomas to avoid destruction by the host's immune system. Macrophages and [[dendritic cell]]s in the granulomas are unable to present antigen to lymphocytes; thus the immune response is suppressed.<ref>{{cite journal | vauthors = Bozzano F, Marras F, De Maria A | title = Immunology of tuberculosis | journal = Mediterranean Journal of Hematology and Infectious Diseases | volume = 6 | issue = 1 | page= e2014027 | year = 2014 | pmid = 24804000 | pmc = 4010607 | doi = 10.4084/MJHID.2014.027 }}</ref> Bacteria inside the granuloma can become dormant, resulting in latent infection. Another feature of the granulomas is the development of abnormal cell death ([[necrosis]]) in the center of [[Tubercle (anatomy)|tubercles]]. To the naked eye, this has the texture of soft, white cheese and is termed [[caseous necrosis]].<ref name=Grosset>{{cite journal | vauthors = Grosset J | title = Mycobacterium tuberculosis in the extracellular compartment: an underestimated adversary | journal = Antimicrobial Agents and Chemotherapy | volume = 47 | issue = 3 | pages = 833β36 | date = March 2003 | pmid = 12604509 | pmc = 149338 | doi = 10.1128/AAC.47.3.833-836.2003 }}</ref> If TB bacteria gain entry to the blood stream from an area of damaged tissue, they can spread throughout the body and set up many foci of infection, all appearing as tiny, white tubercles in the tissues.<ref>{{cite book| vauthors = Crowley LV |title=An introduction to human disease: pathology and pathophysiology correlations|year=2010|publisher=Jones and Bartlett|location=Sudbury, MA|isbn=978-0-7637-6591-0|page=374|url=https://books.google.com/books?id=TEiuWP4z_QIC&pg=PA374|edition=8th|url-status=live|archive-url=https://web.archive.org/web/20150906193726/https://books.google.com/books?id=TEiuWP4z_QIC&pg=PA374|archive-date=6 September 2015}}</ref> This severe form of TB disease, most common in young children and those with HIV, is called miliary tuberculosis.<ref>{{cite book| vauthors = Harries AD, Maher D, Graham S |title=TB/HIV a Clinical Manual|year=2005|publisher=World Health Organization (WHO)|location=Geneva|isbn=978-92-4-154634-8|page=75|url=https://books.google.com/books?id=8dfhwKaCSxkC&pg=PA75|edition=2nd|url-status=live|archive-url=https://web.archive.org/web/20150906195514/https://books.google.com/books?id=8dfhwKaCSxkC&pg=PA75|archive-date=6 September 2015}}</ref> People with this disseminated TB have a high fatality rate even with treatment (about 30%).<ref name=Gho2008>{{cite book| vauthors = Habermann TM, Ghosh A |title=Mayo Clinic internal medicine: concise textbook|year=2008|publisher=Mayo Clinic Scientific Press|location=Rochester, MN|isbn=978-1-4200-6749-1|page=789|url=https://books.google.com/books?id=YJtodBwNxokC&pg=PA789|url-status=live|archive-url=https://web.archive.org/web/20150906190055/https://books.google.com/books?id=YJtodBwNxokC&pg=PA789|archive-date=6 September 2015}}</ref><ref>{{cite journal | vauthors = Jacob JT, Mehta AK, Leonard MK | title = Acute forms of tuberculosis in adults | journal = The American Journal of Medicine | volume = 122 | issue = 1 | pages = 12β17 | date = January 2009 | pmid = 19114163 | doi = 10.1016/j.amjmed.2008.09.018 }}</ref> In many people, the infection waxes and wanes. Tissue destruction and necrosis are often balanced by healing and [[fibrosis]].<ref name=Grosset/> Affected tissue is replaced by scarring and cavities filled with caseous necrotic material. During active disease, some of these cavities are joined to the air passages ([[bronchi]]) and this material can be coughed up. It contains living bacteria and thus can spread the infection. Treatment with appropriate [[antibiotic]]s kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.<ref name=Grosset/> {{Clear}} Summary: Please note that all contributions to Christianpedia may be edited, altered, or removed by other contributors. If you do not want your writing to be edited mercilessly, then do not submit it here. You are also promising us that you wrote this yourself, or copied it from a public domain or similar free resource (see Christianpedia:Copyrights for details). Do not submit copyrighted work without permission! 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