Sarcoidosis pathophysiology: Difference between revisions

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==Overview==
==Overview==


==Pathophysiology==
==Pathophysiology==  
No direct cause of sarcoidosis has been identified, although there have been reports of cell wall deficient [[bacteria]] that may be possible pathogens.<ref>Almenoff PL, Johnson A, Lesser M, Mattman LH. ''Growth of acid fast L forms from the blood of patients with sarcoidosis.'' Thorax 1996;51:530-3. PMID 8711683.</ref> These bacteria are not identified in standard laboratory analysis. It has been thought that there may be a hereditary factor because some families have multiple members with sarcoidosis. To date, no reliable genetic markers have been identified, and an alternate hypothesis is that family members share similar exposures to environmental pathogens. There have also been reports of transmission of sarcoidosis via [[organ transplant]]s.<ref>Padilla ML, Schilero GJ, Teirstein AS. ''Donor-acquired sarcoidosis.'' Sarcoidosis Vasc Diffuse Lung Dis 2002;19:18-24. PMID 12002380.</ref>.
 
Sarcoid granulomas are suggested to have formed with HLA-mediated processing of antigens by macrophages.<ref>Goldman's Cecil Medicine,24th Edition.</ref>. The process is driven by CD4+ helper T cells. There is increased levels of T cell–derived TH1 cytokines such as IL-2 and IFN-γ, resulting in T-cell expansion and macrophage activation, respectively. Increased levels of several cytokines in the local environment (IL-8, TNF, macrophage inflammatory protein 1α) that favor recruitment of additional T cells and monocytes and contribute to the formation of granulomas. TNF in particular is released at high levels by activated alveolar macrophages.<ref>Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition, 8th ed.</ref><ref name="pmid21750528">{{cite journal| author=Chen ES, Moller DR, Medscape| title=Sarcoidosis--scientific progress and clinical challenges. | journal=Nat Rev Rheumatol | year= 2011 | volume= 7 | issue= 8 | pages= 457-67 | pmid=21750528 | doi=10.1038/nrrheum.2011.93 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21750528  }} </ref>
 
Sarcoidosis frequently causes a dysregulation of [[vitamin D]] production with an increase in extrarenal (outside the kidney) production.<ref>Barbour GL, Coburn JW, Slatopolsky E, Norman AW, Horst RL. ''Hypercalcemia in an anephric patient with sarcoidosis: evidence for extrarenal generation of 1,25-dihydroxyvitamin D.'' N Engl J Med 1981;305:440-3. PMID 6894783.</ref> Specifically, [[macrophages]] inside the granulomas convert vitamin D to its active form, resulting in elevated levels of the hormone 1,25-dihydroxyvitamin D and symptoms of [[hypervitaminosis D]] that may include [[fatigue (physical)|fatigue]], [[lack of strength]] or energy, [[irritability]], [[metallic taste]], temporary [[memory loss]] or cognitive problems. Physiological compensatory responses (e.g. suppression of the [[parathyroid hormone]] levels) may mean the patient does not develop frank [[hypercalcemia]].
 
Sarcoidosis has been associated with [[celiac disease]]. Celiac disease is a condition in which there is a chronic reaction to certain protein chains, commonly referred to as glutens, found in some cereal grains. This reaction causes destruction of the villi in the small intestine, with resulting malabsorption of nutrients.
 
While disputed, some cases have been determined to be caused by inhalation of the dust from the collapse of the World Trade Center after the September 11, 2001 attacks.<ref>[http://www.nytimes.com/2007/05/24/nyregion/24dust.html ''New York Times'' article, May 24, 2007]</ref> ''See [[Health effects arising from the September 11, 2001 attacks]] for more information.''
 
Gallium-67 citrate is useful for diagnosing suspected sarcoidosis and evaluation of treatment response. It is more sensitive than radiographic images on diagnosis of Sarcoidosis.


==Histopathological Findings==
==Histopathological Findings==
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[[Image:Sarcoidosis lymph node case 001.jpg|left|thumb|400px|This is a low-power photomicrograph of a lymph node. Note the rather pale-pink color of the tissue with dark-staining cells found in only a few scattered areas. These darker cells represent the original lymphocytes of this lymphoid organ.]]
[[Image:Sarcoidosis lymph node case 001.jpg|left|thumb|400px|This is a low-power photomicrograph of a lymph node. Note the rather pale-pink color of the tissue with dark-staining cells found in only a few scattered areas. These darker cells represent the original lymphocytes of this lymphoid organ.]]
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[[Image:Sarcoidosis lymph node case 002.jpg|left|thumb|400px|This photomicrograph of lymph node tissue illustrates a paucity of lymphocytes as well as numerous small, pale-staining nodules (arrows) throughout the tissue.]]
[[Image:Sarcoidosis lymph node case 002.jpg|left|thumb|400px|This photomicrograph of lymph node tissue illustrates a paucity of lymphocytes as well as numerous small, pale-staining nodules (arrows) throughout the tissue.]]
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[[Image:Sarcoidosis lymph node case 003.jpg|left|thumb|400px|This is a photomicrograph of the small nodules (arrows) seen in the previous image. Close examination reveals that they are composed of large macrophages (epithelioid macrophages). These small granulomas form multiple series of reaction centers throughout the lymph node. Note the remaining lymphocytes surrounding the granulomas.]]
[[Image:Sarcoidosis lymph node case 003.jpg|left|thumb|400px|This is a photomicrograph of the small nodules (arrows) seen in the previous image. Close examination reveals that they are composed of large macrophages (epithelioid macrophages). These small granulomas form multiple series of reaction centers throughout the lymph node. Note the remaining lymphocytes surrounding the granulomas.]]
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[[Image:Sarcoidosis lymph node case 004.jpg|left|thumb|400px|This photomicrograph of a single granuloma illustrates the individual macrophages (arrows) which make up the bulk of this tissue. There is an absence of necrosis in the center of the lesions in this case.]]
[[Image:Sarcoidosis lymph node case 004.jpg|left|thumb|400px|This photomicrograph of a single granuloma illustrates the individual macrophages (arrows) which make up the bulk of this tissue. There is an absence of necrosis in the center of the lesions in this case.]]
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[[Image:Sarcoidosis lymph node case 005.jpg|left|thumb|400px|This is a photomicrograph of a multinucleated giant cell (1). In the center of this foreign body-containing giant cell there is a small asteroid body (2). There is no functional significance to this asteroid body.]]
[[Image:Sarcoidosis lymph node case 005.jpg|left|thumb|400px|This is a photomicrograph of a multinucleated giant cell (1). In the center of this foreign body-containing giant cell there is a small asteroid body (2). There is no functional significance to this asteroid body.]]
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[[Image:Sarcoidosis lymph node case 006.jpg|left|thumb|400px|This is a higher-power photomicrograph of an asteroid body (arrow) inside of a multinucleated giant cell.]]
[[Image:Sarcoidosis lymph node case 006.jpg|left|thumb|400px|This is a higher-power photomicrograph of an asteroid body (arrow) inside of a multinucleated giant cell.]]
<br clear="left"/>
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==References==
==References==

Revision as of 01:48, 6 February 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:

Overview

Pathophysiology

Histopathological Findings

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

This is a low-power photomicrograph of a lymph node. Note the rather pale-pink color of the tissue with dark-staining cells found in only a few scattered areas. These darker cells represent the original lymphocytes of this lymphoid organ.


This photomicrograph of lymph node tissue illustrates a paucity of lymphocytes as well as numerous small, pale-staining nodules (arrows) throughout the tissue.


This is a photomicrograph of the small nodules (arrows) seen in the previous image. Close examination reveals that they are composed of large macrophages (epithelioid macrophages). These small granulomas form multiple series of reaction centers throughout the lymph node. Note the remaining lymphocytes surrounding the granulomas.


This photomicrograph of a single granuloma illustrates the individual macrophages (arrows) which make up the bulk of this tissue. There is an absence of necrosis in the center of the lesions in this case.


This is a photomicrograph of a multinucleated giant cell (1). In the center of this foreign body-containing giant cell there is a small asteroid body (2). There is no functional significance to this asteroid body.


This is a higher-power photomicrograph of an asteroid body (arrow) inside of a multinucleated giant cell.


References

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