|
|
Line 286: |
Line 286: |
| ==Hereditary hemochromatosis== | | ==Hereditary hemochromatosis== |
| :''For secondary causes see [[secondary hemochromatosis]]''. | | :''For secondary causes see [[secondary hemochromatosis]]''. |
| ===General===
| | {{Main|Hereditary hemochromatosis}} |
| Epidemiology:
| |
| *Genetic defect - ''HFE gene''.<ref name=omim613609>{{OMIM|613609}}</ref>
| |
| **One mutation (C282Y mutation) in up to 12.5% of people in populations of northern and central European origin.<ref name=pmid18192769>{{cite journal |author=Weinberg ED |title=Survival advantage of the hemochromatosis C282Y mutation |journal=Perspect. Biol. Med. |volume=51 |issue=1 |pages=98-102 |year=2008 |pmid=18192769 |doi=10.1353/pbm.2008.0001 |url=}}</ref>
| |
| **Homozygotes get the disease.<ref name=omim613609>{{OMIM|613609}}</ref>
| |
| *Onset in males earlier than females (due to menses).
| |
| *Mutation thought to confer survival advantage - several theories (increased resistance to [[TB]], S. typhi vs. decreased iron deficiency/increased iron absorption).<ref name=pmid18192769/>
| |
| | |
| Associated pathology (mnemonic: '''h'''emochromatosis '''c'''an '''c'''ause '''d'''eposits '''a'''nywhere''):<ref>URL: [http://en.wikibooks.org/wiki/USMLE_Step_2_Review http://en.wikibooks.org/wiki/USMLE_Step_2_Review]. Accessed on: 15 March 2012.</ref><ref name=pmid19034258>{{Cite journal | last1 = Fix | first1 = OK. | last2 = Kowdley | first2 = KV. | title = Hereditary hemochromatosis. | journal = Minerva Med | volume = 99 | issue = 6 | pages = 605-17 | month = Dec | year = 2008 | doi = | PMID = 19034258 }}</ref>
| |
| *Hypogonadism.
| |
| *[[Cirrhosis]] and [[HCC]].
| |
| *[[Cardiomyopathy]] - [[DCM]] (esp. with ''his63asp'' mutation),<ref name=pmid11040018>{{Cite journal | last1 = Mahon | first1 = NG. | last2 = Coonar | first2 = AS. | last3 = Jeffery | first3 = S. | last4 = Coccolo | first4 = F. | last5 = Akiyu | first5 = J. | last6 = Zal | first6 = B. | last7 = Houlston | first7 = R. | last8 = Levin | first8 = GE. | last9 = Baboonian | first9 = C. | title = Haemochromatosis gene mutations in idiopathic dilated cardiomyopathy. | journal = Heart | volume = 84 | issue = 5 | pages = 541-7 | month = Nov | year = 2000 | doi = | PMID = 11040018 }}</ref> may be [[RCM]].
| |
| *[[Diabetes mellitus]] (bronze diabetes).
| |
| *Arthropathy.<ref name=pmid11148720>{{Cite journal | last1 = von Kempis | first1 = J. | title = Arthropathy in hereditary hemochromatosis. | journal = Curr Opin Rheumatol | volume = 13 | issue = 1 | pages = 80-3 | month = Jan | year = 2001 | doi = | PMID = 11148720 }}</ref>
| |
| | |
| Pathophysiology:
| |
| *Iron overload -> [[cirrhosis]].
| |
| | |
| ===Microscopic===
| |
| Features:
| |
| *Periportal iron deposition (early).
| |
| **Late stage disease has diffuse iron deposition.
| |
| *Brown granular - may vaguely look like [[lipofuscin]] on [[H&E]].
| |
| | |
| Notes:
| |
| *Iron in the bile ducts and endothelium used to be though specific of hereditary hemochromatosis.<ref>MG. 17 September 2009.</ref>
| |
| **It is now thought to just reflect the severity of iron deposition, i.e. if the bile ducts and endothelium have iron - it is severe.
| |
| | |
| DDx - secondary hemochromatosis:
| |
| *[[Myelodysplastic syndrome]].
| |
| *Chronic hemolysis.
| |
| *Alcoholic liver disease; iron deposition common in [[cirrhosis]].
| |
| | |
| ====Images====
| |
| <gallery>
| |
| Image:Hemosiderosis_high_mag.jpg | Hemosiderosis - iron stain. (WC)
| |
| </gallery>
| |
| www:
| |
| *[http://path.upmc.edu/cases/case77/path.html Hemochromatosis (upmc.edu)].
| |
| ===Stains===
| |
| Iron stain +ve -- '''important'''.
| |
| *Light blue haze is not enough.
| |
| **Must be separated from ''siderosis'' -- iron in Kupffer cells.
| |
| | |
| ===Molecular===
| |
| *PCR - '''diagnostic''' - see ''[[molecular pathology tests]]''.
| |
|
| |
|
| ==Wilson disease== | | ==Wilson disease== |