Lower gastrointestinal bleeding pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
 
(31 intermediate revisions by 3 users not shown)
Line 4: Line 4:
==Overview==
==Overview==


 
[[Superior mesenteric artery]] and [[inferior mesenteric artery]] are the two major [[blood vessels]] that supply [[lower gastrointestinal tract]]. Disruption of  blood vessel junction, formed by these two vessels, by any of the disease process results in bleeding. [[Diverticulosis]] is the most common etiology of lower GI bleeding accounting for 30% of all cases, followed by [[Anorectal|ano-rectal disease]], [[ischemia]] of bowel, [[inflammatory bowel disease]] ([[Inflammatory bowel disease|IBD]]), [[Colorectal cancer|neoplasia]], and [[Angiodysplasia|arteriovenous (AV) malformations]]. The characteristic gross and microscopic findings of lower [[Gastrointestinal tract|gastrointestinal tracts]] depends upon the underlying pathology.
==Pathophysiology==
==Pathophysiology==
===Blood supply===
===Blood supply===
* The SMA and IMA are connected by the marginal artery of Drummond.  
* [[Superior mesenteric artery]] and [[inferior mesenteric artery]] are the two major [[blood vessels]] that supply [[lower gastrointestinal tract]].<ref name="pmid11355897">{{cite journal |vauthors=Geboes K, Geboes KP, Maleux G |title=Vascular anatomy of the gastrointestinal tract |journal=Best Pract Res Clin Gastroenterol |volume=15 |issue=1 |pages=1–14 |year=2001 |pmid=11355897 |doi=10.1053/bega.2000.0152 |url=}}</ref><ref name="pmid26140727">{{cite journal |vauthors=Granger DN, Holm L, Kvietys P |title=The Gastrointestinal Circulation: Physiology and Pathophysiology |journal=Compr Physiol |volume=5 |issue=3 |pages=1541–83 |year=2015 |pmid=26140727 |doi=10.1002/cphy.c150007 |url=}}</ref><ref name="urlThe Gastrointestinal Circulation - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK53092/ |title=The Gastrointestinal Circulation - NCBI Bookshelf |format= |work= |accessdate=}}</ref>
* This vascular arcade runs in the mesentery close to the bowel.
* The [[superior mesenteric artery]] and [[inferior mesenteric artery]] are interconnected through a branch of anastomosis between various branches which are collectively called as [[Marginal artery of the colon|marginal artery]] of Drummond. 
* As patients age, there is increased incidence of occlusion of the IMA.
* This [[vascular]] arcade runs in the [[mesentery]] close to the [[bowel]].
* The left colon stays perfused, primarily because of the marginal artery.
{| border="1" cellpadding="5" cellspacing="0" align="center" |class="wikitable"
{| border="1" cellpadding="5" cellspacing="0" align="center" |class="wikitable"
! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" |Lower GI Tract
! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" |Lower GI Tract
Line 16: Line 15:
! align="center" style="background:#4479BA; color: #FFFFFF;" |Venous Drainage  
! align="center" style="background:#4479BA; color: #FFFFFF;" |Venous Drainage  
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |Midgut
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Midgut]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Distal duodenum jejunum
* [[Duodenum|Distal duodenum]]
* Ileum
* [[Jejunum]]
* Appendix
* [[Ileum]]
* Cecum
* [[Appendix]]
* Ascending colon
* [[Cecum]]
* Hepatic flexure
* [[Ascending colon]]
* Proximal transverse colon.
* [[Hepatic flexure]]
* [[Transverse colon|Proximal transverse colon]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Superior mesenteric artery (SMA)
* [[Superior mesenteric artery]] ([[Superior mesenteric artery|SMA]])
** [[Ileocolic artery]]
** [[Right colic artery]]
** [[Middle colic artery|Middle colic branches]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Portal system.
* [[Superior mesenteric vein]]
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |Hindgut
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Hindgut]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Distal one-third of the transverse colon
* [[Distal]] one-third of the [[transverse colon]]
* Splenic flexure
* [[Splenic flexure]]
* Descending colon,
* [[Descending colon]]
* Sigmoid colon
* [[Sigmoid colon]]
* Rectumhu
* [[Rectum]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Inferior mesenteric artery (IMA)
* [[Inferior mesenteric artery]] ([[Inferior mesenteric artery|IMA]])
** [[Left colic artery]]
** [[Sigmoid arteries|Sigmoid artery]]
** [[Superior rectal artery|Superior rectal branches]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Portal system '''<sup>ɸ</sup>'''
* [[Portal venous system|Portal system]] '''<sup>ɸ</sup>'''
|-
|-
| colspan="4" style="padding: 5px 5px; background: #F5F5F5;" align="center" |ɸ -Except lower rectum, which drains into the systemic circulation.
| colspan="4" style="padding: 5px 5px; background: #F5F5F5;" align="center" |ɸ -Except [[Rectum|lower rectum]], which drains into the [[systemic circulation]].
|}
|}


Line 48: Line 54:


===Pathogenesis===
===Pathogenesis===
The pathogenesis of lower gastrointestinal bleeding can be discussed based on the etiology. Diverticulosis is the most common etiology of lower GI bleeding accounting for 30% of all cases, followed by anorectal disease, ischemia, inflammatory bowel disease (IBD), neoplasia and arteriovenous (AV) malformations.
The pathogenesis of lower gastrointestinal bleeding can be discussed based on the etiology. [[Diverticulosis]] is the most common etiology of lower GI bleeding accounting for 30% of all cases, followed by [[anorectal]] disease, [[ischemia]], [[inflammatory bowel disease]] ([[Inflammatory bowel disease|IBD]]), [[Colorectal cancer|neoplasia]], and [[Angiodysplasia|arteriovenous (AV) malformations]].
*'''<u>Diverticulosis</u>'''
*'''<u>[[Diverticulosis]]</u>'''
**The colonic wall weakens with age and results in the formation of saclike protrusions known as diverticula.
**The [[Intestinal wall|colonic wall]] weakens with age and results in the formation of sac-like protrusions known as [[Diverticulum|diverticula]].<ref name="pmid20011269">{{cite journal |vauthors=Hobson KG, Roberts PL |title=Etiology and pathophysiology of diverticular disease |journal=Clin Colon Rectal Surg |volume=17 |issue=3 |pages=147–53 |year=2004 |pmid=20011269 |pmc=2780060 |doi=10.1055/s-2004-832695 |url=}}</ref><ref name="pmid20011276">{{cite journal |vauthors=Maykel JA, Opelka FG |title=Colonic diverticulosis and diverticular hemorrhage |journal=Clin Colon Rectal Surg |volume=17 |issue=3 |pages=195–204 |year=2004 |pmid=20011276 |pmc=2780065 |doi=10.1055/s-2004-832702 |url=}}</ref><ref name="pmid17468551">{{cite journal |vauthors=Comparato G, Pilotto A, Franzè A, Franceschi M, Di Mario F |title=Diverticular disease in the elderly |journal=Dig Dis |volume=25 |issue=2 |pages=151–9 |year=2007 |pmid=17468551 |doi=10.1159/000099480 |url=}}</ref><ref name="pmid20676256">{{cite journal |vauthors=Matrana MR, Margolin DA |title=Epidemiology and pathophysiology of diverticular disease |journal=Clin Colon Rectal Surg |volume=22 |issue=3 |pages=141–6 |year=2009 |pmid=20676256 |pmc=2780269 |doi=10.1055/s-0029-1236157 |url=}}</ref>
**These protrusions generally occur at the junction of blood vessel penetrating through the mucosa and circular muscle fibers of the colon.
**These protrusions generally occur at the junction of [[blood vessel]] penetrating through the [[mucosa]] and circular [[muscle fibers]] of the [[colon]].
**Diverticula are most common in the descending and sigmoid colon.
**[[Hemorrhage]] results from rupture of the intramural branches ([[vasa recta]]) of the [[marginal artery]] at the dome of a [[diverticulum]] and can give rise to a massive, life-threatening LGIB.
**Despite the majority of diverticula being on the left side of the colon, diverticular bleeding originates from the right side of the colon in 50% to 90% of instances.
**Most of the time bleeding from diverticulosis stops spontaneously, however, in about 5% of patients, the bleeding can be massive and life-threatening.
[[Image:Sigmoid diverticulum (diagram).jpg|thumb|center|400px|Diagram of sigmoid diverticulum<br>Source:By Anpol42 (Own work) [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons]]
[[Image:Sigmoid diverticulum (diagram).jpg|thumb|center|400px|Diagram of sigmoid diverticulum<br>Source:By Anpol42 (Own work) [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons]]
*'''<u>Anorectal disease</u>'''
*'''<u>Anorectal disease</u>'''
:*Hemorrhoids and anal fissures are the most common disease under anorectal disease responsible for GI bleeding.
:*Hemorrhoids are defined as [[Swelling (medical)|swelling]] and [[inflammation]] of [[veins]] in the [[Rectum|rectal]] and [[Anus|anal region]]
:*Hemorrhoids are engorged vessels in the normal anal cushions. When swollen, this tissue is very friable and susceptible to trauma, which leads to painless, bright red bleeding.
:*Hemorrhoids can be either internal or external based on their relation to dentate line.
:*Anal fissures are defined as a tear in the anal mucosa. With the passage of stool, the mucosa continues to tear and leads to bright red bleeding.  
:*The first step in the pathogenesis of either type of hemorrhoids is weakening of the surrounding connective tissue and vein wall.<ref name="pmid22563187">{{cite journal |vauthors=Lohsiriwat V |title=Hemorrhoids: from basic pathophysiology to clinical management |journal=World J. Gastroenterol. |volume=18 |issue=17 |pages=2009–17 |year=2012 |pmid=22563187 |pmc=3342598 |doi=10.3748/wjg.v18.i17.2009 |url=}}</ref><ref name="pmid22379400">{{cite journal |vauthors=Sanchez C, Chinn BT |title=Hemorrhoids |journal=Clin Colon Rectal Surg |volume=24 |issue=1 |pages=5–13 |year=2011 |pmid=22379400 |pmc=3140328 |doi=10.1055/s-0031-1272818 |url=}}</ref><ref name="pmid22563187">{{cite journal |vauthors=Lohsiriwat V |title=Hemorrhoids: from basic pathophysiology to clinical management |journal=World J. Gastroenterol. |volume=18 |issue=17 |pages=2009–17 |year=2012 |pmid=22563187 |pmc=3342598 |doi=10.3748/wjg.v18.i17.2009 |url=}}</ref>
*'''<u>Mesenteric Ischemia</u>'''
:*Weakening of blood vessels can result in bleeding under pressure.
:*Mesenteric ischemia results when there is inadequate blood supply at the level of the small intestine.
:*An anal fissure can be defined as disruption or tear in the mucosal surface of the skin.
:*2 or more vessels (celiac, SMA, or IMA) must be involved for symptoms to occur.
:*During defecation, due to increased pressure which can exaggerate the tears may  present as bright red rectal bleeding with severe periodic pain.<ref name="pmid3140330">{{cite journal |vauthors=Holland RA, Rimes AF, Comis A, Tyndale-Biscoe CH |title=Oxygen carriage and carbonic anhydrase activity in the blood of a marsupial, the Tammar wallaby (Macropus eugenii), during early development |journal=Respir Physiol |volume=73 |issue=1 |pages=69–86 |year=1988 |pmid=3140330 |doi= |url=}}</ref>
:*Non occlusive mesenetric ischemia affects critically ill patients who are vasopressor-dependent.
*'''<u>[[Mesenteric ischemia|Mesenteric Ischemia]]</u>'''
:*Venous thrombosis of the visceral vessels can also precipitate an acute ischemic event.
:*[[Mesenteric ischemia]] results when there is inadequate blood supply at the level of the [[small intestine]].<ref name="pmid9146726">{{cite journal |vauthors=Krupski WC, Selzman CH, Whitehill TA |title=Unusual causes of mesenteric ischemia |journal=Surg. Clin. North Am. |volume=77 |issue=2 |pages=471–502 |year=1997 |pmid=9146726 |doi= |url=}}</ref><ref name="pmid21326562">{{cite journal |vauthors=Walker TG |title=Mesenteric ischemia |journal=Semin Intervent Radiol |volume=26 |issue=3 |pages=175–83 |year=2009 |pmid=21326562 |pmc=3036494 |doi=10.1055/s-0029-1225662 |url=}}</ref><ref name="pmid18625147">{{cite journal |vauthors=Berland T, Oldenburg WA |title=Acute mesenteric ischemia |journal=Curr Gastroenterol Rep |volume=10 |issue=3 |pages=341–6 |year=2008 |pmid=18625147 |doi= |url=}}</ref><ref name="pmid26909235">{{cite journal |vauthors=Mastoraki A, Mastoraki S, Tziava E, Touloumi S, Krinos N, Danias N, Lazaris A, Arkadopoulos N |title=Mesenteric ischemia: Pathogenesis and challenging diagnostic and therapeutic modalities |journal=World J Gastrointest Pathophysiol |volume=7 |issue=1 |pages=125–30 |year=2016 |pmid=26909235 |pmc=4753178 |doi=10.4291/wjgp.v7.i1.125 |url=}}</ref>
*'''<u>Ischemic Colitis</u>'''
:*2 or more vessels ([[Celiac artery|celiac]], [[Superior mesenteric artery|SMA]], or [[Inferior mesenteric artery|IMA]]) must be involved for bleeding to occur.
:*Ischemic colitis is caused by poor perfusion of the colon, which results in the inability of that area of the colon to meet its metabolic demands.  
:*Decreased blood supply can occur due to obstruction of blood vessel either by emobolus or due to vasoconstriction effect of drugs.
:*It can be gangrenous or nongangrenous, acute, transient, or chronic.
:*Decreased blood supply initiates necrosis of mucosal surface of intestine.
:*The left colon is predominantly affected, with the splenic flexure having increased susceptibility.
:*unopposed blood deprivation leads to trans-mural necrosis and ultimately sloughing of the tissues with associated bleeding.
:*Intraluminal hemorrhage occurs as the mucosa becomes necrotic, sloughs, and bleeds.
*'''<u>[[Ischemic colitis|Ischemic Colitis]]</u>'''
:*Damage to the tissue is caused both with the ischemic insult as well as reperfusion injury.
:*Ischemic colitis is a condition in which injury of the [[large intestine]] results from decreased blood supply.<ref name="pmid26034405">{{cite journal |vauthors=FitzGerald JF, Hernandez Iii LO |title=Ischemic colitis |journal=Clin Colon Rectal Surg |volume=28 |issue=2 |pages=93–8 |year=2015 |pmid=26034405 |pmc=4442720 |doi=10.1055/s-0035-1549099 |url=}}</ref><ref name="pmid19109863">{{cite journal |vauthors=Theodoropoulou A, Koutroubakis IE |title=Ischemic colitis: clinical practice in diagnosis and treatment |journal=World J. Gastroenterol. |volume=14 |issue=48 |pages=7302–8 |year=2008 |pmid=19109863 |pmc=2778113 |doi= |url=}}</ref><ref name="pmid25504381">{{cite journal |vauthors=Rania H, Mériam S, Rym E, Hyafa R, Amine A, Najet BH, Lassad G, Mohamed TK |title=Ischemic colitis in five points: an update 2013 |journal=Tunis Med |volume=92 |issue=5 |pages=299–303 |year=2014 |pmid=25504381 |doi= |url=}}</ref>
*'''<u>Inflammatory Bowel Disease</u>'''
:*The [[Colon (anatomy)|colon]] is most commonly involved due the presence of water shed areas ( splenic flexure and hepatic flexure).
:*In Crohn's disease T cell activation stimulates interleukin (IL)-12 and tumor necrosis factor (TNF)-a, which causes chronic inflammation and tissue injury.  
:*Similar to mesentric ischemia bleeding occurs due to necrosis and sloughing of mucosal membrane.
:*Initially, inflammation starts focally around the crypts, followed by superficial ulceration of the mucosa.
*'''<u>Inflammatory Bowel Disease</u>'''<ref name="pmid28261018">{{cite journal |vauthors=Kim DH, Cheon JH |title=Pathogenesis of Inflammatory Bowel Disease and Recent Advances in Biologic Therapies |journal=Immune Netw |volume=17 |issue=1 |pages=25–40 |year=2017 |pmid=28261018 |pmc=5334120 |doi=10.4110/in.2017.17.1.25 |url=}}</ref><ref name="pmid11781268">{{cite journal |vauthors=Hendrickson BA, Gokhale R, Cho JH |title=Clinical aspects and pathophysiology of inflammatory bowel disease |journal=Clin. Microbiol. Rev. |volume=15 |issue=1 |pages=79–94 |year=2002 |pmid=11781268 |pmc=118061 |doi= |url=}}</ref>
:*The deep mucosal layers are then invaded in a noncontinuous fashion, and noncaseating granulomas form, which can invade through the entire thickness of the bowel and into the mesentery and surrounding structures.
**'''[[Crohn's disease]]'''
:*In ulcerative colitis T cells cytotoxic to the colonic epithelium accumulate in the lamina propria, accompanied by B cells that secrete immunoglobulin G (IgG) and IgE.  
***In [[Crohn's disease]], [[T cell]] activation stimulates [[Interleukin 12|interleukin (IL)-12]] and [[Tumor necrosis factor alpha|tumor necrosis factor (TNF)-α]], resulting in [[chronic]] [[inflammation]] and tissue injury.<ref name="pmid4447044">{{cite journal |vauthors=Woźniak-Parnowska W, Werakso B |title=[Comparative studies of microbiological purity of ointments by the direct culture method and use of membrane filters] |language=Polish |journal=Acta Pol Pharm |volume=31 |issue=6 |pages=819–23 |year=1974 |pmid=4447044 |doi= |url=}}</ref><ref name="pmid24395894">{{cite journal |vauthors=Mazal J |title=Crohn disease: pathophysiology, diagnosis, and treatment |journal=Radiol Technol |volume=85 |issue=3 |pages=297–316; quiz 317–20 |year=2014 |pmid=24395894 |doi= |url=}}</ref><ref name="pmid2694136">{{cite journal |vauthors=Jewell DP |title=Aetiology and pathogenesis of ulcerative colitis and Crohn's disease |journal=Postgrad Med J |volume=65 |issue=768 |pages=718–9 |year=1989 |pmid=2694136 |pmc=2429831 |doi= |url=}}</ref><ref name="pmid16819502">{{cite journal |vauthors=Sartor RB |title=Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis |journal=Nat Clin Pract Gastroenterol Hepatol |volume=3 |issue=7 |pages=390–407 |year=2006 |pmid=16819502 |doi=10.1038/ncpgasthep0528 |url=}}</ref><ref name="pmid15656711">{{cite journal |vauthors=Head K, Jurenka JS |title=Inflammatory bowel disease. Part II: Crohn's disease--pathophysiology and conventional and alternative treatment options |journal=Altern Med Rev |volume=9 |issue=4 |pages=360–401 |year=2004 |pmid=15656711 |doi= |url=}}</ref><ref name="pmid24415861">{{cite journal |vauthors=Zhang YZ, Li YY |title=Inflammatory bowel disease: pathogenesis |journal=World J. Gastroenterol. |volume=20 |issue=1 |pages=91–9 |year=2014 |pmid=24415861 |pmc=3886036 |doi=10.3748/wjg.v20.i1.91 |url=}}</ref>
:*This results in inflammation of the crypts of Lieberkuhn, with abscesses and pseudopolyps.
***TNF-alpha induces expression of adhesion factors that allow for inflammatory cells to infiltrate and activates macrophages resulting in granuloma formations
:*Ulcerative colitis generally begins at the rectum and is a continuous process confined exclusively to the colon.
***The inflammatory response invades through the entire thickness of the bowel wall weakening the surrounding blood vessels resulting in bleeding.
:* '''<u>Ulcerative colitis</u>'''
:** In [[ulcerative colitis]], [[T cells]], [[cytotoxic]] to the colonic epithelium, accumulate in the [[lamina propria]], accompanied by [[B cells]] that secrete [[immunoglobulin G]] ([[Immunoglobulin G|IgG]]) and [[Immunoglobulin E|IgE]].<ref name="pmid16819502">{{cite journal |vauthors=Sartor RB |title=Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis |journal=Nat Clin Pract Gastroenterol Hepatol |volume=3 |issue=7 |pages=390–407 |year=2006 |pmid=16819502 |doi=10.1038/ncpgasthep0528 |url=}}</ref><ref name="pmid27914657">{{cite journal |vauthors=Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF |title=Ulcerative colitis |journal=Lancet |volume=389 |issue=10080 |pages=1756–1770 |year=2017 |pmid=27914657 |doi=10.1016/S0140-6736(16)32126-2 |url=}}</ref><ref name="pmid11830216">{{cite journal |vauthors=Farrell RJ, Peppercorn MA |title=Ulcerative colitis |journal=Lancet |volume=359 |issue=9303 |pages=331–40 |year=2002 |pmid=11830216 |doi=10.1016/S0140-6736(02)07499-8 |url=}}</ref><ref name="pmid1516252">{{cite journal |vauthors=Rönnblom LE, Janson ET, Perers A, Oberg KE, Alm GV |title=Characterization of anti-interferon-alpha antibodies appearing during recombinant interferon-alpha 2a treatment |journal=Clin. Exp. Immunol. |volume=89 |issue=3 |pages=330–5 |year=1992 |pmid=1516252 |pmc=1554468 |doi= |url=}}</ref>
:** This results in [[inflammation]] of the [[crypts of Lieberkuhn]], with [[abscesses]] and [[pseudopolyps]] along with
:** rupturing of minute [[blood vessels]] in [[mucosa]] resulting in bleeding.
*'''<u>Neoplasia</u>'''
*'''<u>Neoplasia</u>'''
:*Colon carcinoma follows a distinct progression from polyp to cancer.
**Colon cancer arises mostly due to sporadic mutations that originates from the [[epithelial cells]] of [[colon]] or [[rectum]].
:*Mutations of multiple genes are required for the formation of adenocarcinoma, including the APC gene, Kras, DCC, and p53.  
**Genetic instability/mutation results in [[Epigenetic|epigenetic alteration]], [[chronic inflammation]], [[oxidative stress]], and intestinal [[microbiota]].<ref name="pmid12702969">{{cite journal |vauthors=Itzkowitz S |title=Colon carcinogenesis in inflammatory bowel disease: applying molecular genetics to clinical practice |journal=J. Clin. Gastroenterol. |volume=36 |issue=5 Suppl |pages=S70–4; discussion S94–6 |year=2003 |pmid=12702969 |doi= |url=}}</ref><ref name="pmid21530747">{{cite journal |vauthors=Ullman TA, Itzkowitz SH |title=Intestinal inflammation and cancer |journal=Gastroenterology |volume=140 |issue=6 |pages=1807–16 |year=2011 |pmid=21530747 |doi=10.1053/j.gastro.2011.01.057 |url=}}</ref><ref name="pmid19589728">{{cite journal |vauthors=Kraus S, Arber N |title=Inflammation and colorectal cancer |journal=Curr Opin Pharmacol |volume=9 |issue=4 |pages=405–10 |year=2009 |pmid=19589728 |doi=10.1016/j.coph.2009.06.006 |url=}}</ref>
:*Certain hereditary syndromes are also classified by defects in DNA mismatch repair genes and microsatellite instability.
**As [[tumor]] tends to grow slowly it invades the surrounding tissue disrupting the normal blood vessels along with it.
:*These tumors tend to bleed slowly, and patients present with hemocult positive stools and microcytic anemia.
**This is responsible for slow occult bleeding that is found positive on FOBT.
:*Although cancers of the small bowel are much less common than colorectal cancers, they should be ruled out in cases of lower GI bleeding in which no other source is identified.
 
*'''<u>AV Malformation/Angiodysplasia</u>'''
*'''<u>AV Malformation/Angiodysplasia</u>'''
:*In AV malformation direct connections between arteries and veins occur in the colonic submucosa.
:*In [[Arteriovenous malformations|AV malformation]] abnormal connections occur between [[arteries]] and [[veins]].<ref name="pmid8389094">{{cite journal |vauthors=Foutch PG |title=Angiodysplasia of the gastrointestinal tract |journal=Am. J. Gastroenterol. |volume=88 |issue=6 |pages=807–18 |year=1993 |pmid=8389094 |doi= |url=}}</ref><ref name="pmid9048468">{{cite journal |vauthors=Dodda G, Trotman BW |title=Gastrointestinal angiodysplasia |journal=J Assoc Acad Minor Phys |volume=8 |issue=1 |pages=16–9 |year=1997 |pmid=9048468 |doi= |url=}}</ref><ref name="pmid1744847">{{cite journal |vauthors=Kheterpal S |title=Angiodysplasia: a review |journal=J R Soc Med |volume=84 |issue=10 |pages=615–8 |year=1991 |pmid=1744847 |pmc=1295562 |doi= |url=}}</ref><ref name="pmid311247">{{cite journal |vauthors=Athanasoulis CA, Galdabini JJ, Waltman AC, Novelline RA, Greenfield AJ, Ezpeleta ML |title=Angiodysplasia of the colon: a cause of rectal bleeding |journal=Cardiovasc Radiol |volume=1 |issue=1 |pages=3–13 |year=1977 |pmid=311247 |doi= |url=}}</ref><ref name="pmid24138285">{{cite journal |vauthors=Sami SS, Al-Araji SA, Ragunath K |title=Review article: gastrointestinal angiodysplasia - pathogenesis, diagnosis and management |journal=Aliment. Pharmacol. Ther. |volume=39 |issue=1 |pages=15–34 |year=2014 |pmid=24138285 |doi=10.1111/apt.12527 |url=}}</ref>
:*The lack of capillary buffers causes high pressure blood to enter directly into the venous system, making these vessels at high risk of rupture into the bowel lumen.
:*This connections results in blood flow from high pressure arteries to low pressure veins without buffering effects of capillaries.
:*In Angiodysplasia over time, previously healthy blood vessels of the cecum and ascending colon degenerate and become prone to bleeding.
:*The lack of [[capillary]] buffers makes the [[vessels]] weak due to increased blood flow and ultimately bleeding.
:*Although 75% of angiodysplasia cases involve the right colon, they are a significant cause of obscure bleeding and the most common cause of bleeding from the small bowel in the elderly.
:*In [[Angiodysplasia]], with age the connective tissue of the blood vessels become weak.
:*With mild increase in pressure leads to disrupture of vessels leading to painless bleeding.


==Associated Conditions==
==Associated Conditions==
Other diseases that are commonly associated with lower gastrointestinal bleeding include:
*Aortoenteric [[fistula]]
*[[Abdominal aortic aneurysm|Abdominal aortic aneurysms]]
*[[Peutz-Jeghers syndrome]]
*[[Klippel-Trenaunay-Weber syndrome]]
*[[Hereditary hemorrhagic telangiectasia]]
*[[Neurofibromatosis]] 
*[[Blue rubber bleb syndrome]]


==Gross and Microscopic Pathology==
==Gross and Microscopic Pathology==
Line 99: Line 116:
!Microscopic Pathology
!Microscopic Pathology
|-
|-
|Diverticulosis
|[[Diverticulosis]]<ref name="pmid15115923">{{cite journal |vauthors=West AB, Losada M |title=The pathology of diverticulosis coli |journal=J. Clin. Gastroenterol. |volume=38 |issue=5 Suppl 1 |pages=S11–6 |year=2004 |pmid=15115923 |doi= |url=}}</ref>
|
|
* Multiple, small, flask like invaginations
* Numerous visible flask like protrusions along the [[intestinal wall]].
* Thick and corrugated circular muscle with prominent accordion-like mucosal folds.
* Thick and corrugated circular [[muscle fibers]] with mucosal folds.
|
|
* Inflammatory cells  
* Numerous [[Inflammatory cells|cells of inflammation]]
* Intramucosal ganglion cells  
* [[Ganglion cells|Intramucosal ganglion cells]]
* Lymphoid infiltrate
* [[Lymphoid]] infiltrate
* Lymphoglandular complexes
* [[Cryptitis|Mild cryptitis]]
* Mucin depletion
* [[Paneth cells|Paneth cell metaplasia]]
* Mild cryptitis
* [[Ulcers]]
* Achitectural distortion
* Paneth cell metaplasia
* Ulceration 
|-
|-
|Angiodysplasia
|[[Angiodysplasia]]<ref name="pmid4029903">{{cite journal |vauthors=Stamm B, Heer M, Bühler H, Ammann R |title=Mucosal biopsy of vascular ectasia (angiodysplasia) of the large bowel detected during routine colonoscopic examination |journal=Histopathology |volume=9 |issue=6 |pages=639–46 |year=1985 |pmid=4029903 |doi= |url=}}</ref>
|
|
* Tortuous dilation of multiple small submucosal and mucosal blood vessels
* Tortuous dilatation of multiple small [[submucosal]] and [[mucosal]] blood vessels.
|
|
* Dilated and thin-walled vessels in mucosa and submucosa often in clusters.
* Clusters of numerous dilated and thin-walled [[vessels]] in [[mucosa]] and [[Submucosal|submucosa]].
* Surrounding mucosa may be eroded
* Erosion of surrounding [[mucosa]]
|-
|-
|Hemorrhoids
|[[Hemorrhoids]]<ref name="pmid22563187">{{cite journal |vauthors=Lohsiriwat V |title=Hemorrhoids: from basic pathophysiology to clinical management |journal=World J. Gastroenterol. |volume=18 |issue=17 |pages=2009–17 |year=2012 |pmid=22563187 |pmc=3342598 |doi=10.3748/wjg.v18.i17.2009 |url=}}</ref>
|
|
* Tortuous superficial dilations of multiple blood vessels.
* Tortuous superficial dilatations of multiple blood vessels.
|
|
* Dilated, thick-walled, congested submucosal vessels  
* Dilated, thick-walled, [[congested]] [[submucosal]] [[vessels]]
* Papillary endothelial hyperplasia
* [[Papillary]] [[endothelial]] [[hyperplasia]]
* Internal hemorrhoids are lined by rectal or transitional mucosa,
* [[Superficial]] [[ulcerations]]
* External hemorrhoids have a squamous lining
* [[Pagetoid]] dyskeratosis  
* Superficial ulcerations
* Pagetoid dyskeratosis  
|-
|-
|Mesenteric ischemia 
|[[Mesenteric ischemia]] <ref name="pmid1731389">{{cite journal |vauthors=Mitsudo S, Brandt LJ |title=Pathology of intestinal ischemia |journal=Surg. Clin. North Am. |volume=72 |issue=1 |pages=43–63 |year=1992 |pmid=1731389 |doi= |url=}}</ref>
|
|
* Hemorrhagic infarctions
* [[Hemorrhagic]] [[Infarction|infarctions]]


* Ulcerations
* [[Ulcerations]]
* Mucosal plaque
* [[Strictures]]
* Strictures
|
|
* Lamina propria hemorrhage
* [[Hemorrhage]] in [[lamina propria]]
* Superficial epithelial necrosis,
* [[Necrosis]] of superficial [[epithelial cells]] 
* Deep crypts
* Deep crypts
* Minimal inflammation
* [[Fibrosis]]
* Strictures
|-
|-
|Ischemic colitis
|[[Ischemic colitis]]<ref name="pmid1731389">{{cite journal |vauthors=Mitsudo S, Brandt LJ |title=Pathology of intestinal ischemia |journal=Surg. Clin. North Am. |volume=72 |issue=1 |pages=43–63 |year=1992 |pmid=1731389 |doi= |url=}}</ref>
|
|
* Discrete or serpiginous ulcerations (may be discrete or serpiginous)
* Discrete or [[serpiginous]] [[ulcerations]]
* Cobblestone pattern resembling Crohn’s disease
* [[Pseudopolyps]]
* Pseudopolyps resembling ulcerative colitis
* [[Hemorrhagic]] [[Infarction|infarctions]]
* Hemorrhagic infractions
* Frank blood or dark mucus in lumen
* Frank blood or dark mucus in lumen
* Late fibrosis and stricture formation
* [[Strictures]]
|
|
* Hallmarks of ischemic bowel are necrotizing phlebitis and thrombi formation
* [[Necrotizing]] [[phlebitis]]
* Necrosis
* Multiple thrombi  
* Ulceration and granulation tissue extend into submucosa and surrounding smooth muscle fibers of muscularis mucosa
* [[Ulcerations]]
* [[Granulation tissue]] extending into surrounding [[submucosa]] and smooth muscle fibers.
|-
|-
|Crohn's disease 
|[[Crohn's disease]]<ref name="pmid1089084">{{cite journal |vauthors=Price AB, Morson BC |title=Inflammatory bowel disease: the surgical pathology of Crohn's disease and ulcerative colitis |journal=Hum. Pathol. |volume=6 |issue=1 |pages=7–29 |year=1975 |pmid=1089084 |doi= |url=}}</ref><ref name="pmid9537465">{{cite journal |vauthors=Wright CL, Riddell RH |title=Histology of the stomach and duodenum in Crohn's disease |journal=Am. J. Surg. Pathol. |volume=22 |issue=4 |pages=383–90 |year=1998 |pmid=9537465 |doi= |url=}}</ref> 
|
|
* Dull and granular serosa
* Creeping fat
* Creeping fat  
* Thick/rubbery [[intestinal wall]]
* Thick/rubbery intestinal wall (due to edema, inflammation, fibrosis, hypertrophy of muscularis propria)
* [[Strictures]] (string sign on barium enema)
* Strictures (string sign on barium enema)
* Skip areas
* Skip areas
* Aphthous mucosal ulcers
* [[Aphthous ulcers|Aphthous mucosal ulcers]]
|
|
* Superficial or deep ulceration
* Superficial or deep [[ulcerations]]
* Adjacent granulation tissue extending into deep submucosa or below.
* [[Granulation tissue]] extending into surrounding [[submucosa]] and smooth muscle fibers.
* Transmural inflammation with lymphoid aggregates
* Transmural inflammation with lymphoid aggregates
* Goblet cells  
* [[Goblet cells]]
* Focal neutrophils in epithelium and overlying lymphoid aggregates and plasmacytosis
* Focal [[neutrophils]] in [[epithelium]]
* Edematous mucosa and submucosa  
* [[Lymphoid]] aggregates  
* [[Plasmacytosis]]
* Edematous [[mucosa]] and [[submucosa]]
|-
|-
|Ulcerative colitis
|[[Ulcerative colitis]]<ref name="pmid24942757">{{cite journal |vauthors=DeRoche TC, Xiao SY, Liu X |title=Histological evaluation in ulcerative colitis |journal=Gastroenterol Rep (Oxf) |volume=2 |issue=3 |pages=178–92 |year=2014 |pmid=24942757 |pmc=4124271 |doi=10.1093/gastro/gou031 |url=}}</ref>
|
|
* Deep fissuring ulcerations
* Deep fissuring [[ulcerations]]
* Hemorrhagic mucosa  
* [[Hemorrhagic]] [[mucosa]]
* Pseudopolyps  
* [[Pseudopolyps]]
|
|
* Diffuse mononuclear inflammatory infiltrate in lamina propria
* [[Mononuclear cells|Mononuclear]] inflammatory infiltrate in [[lamina propria]]
* Crypt abscesses (neutrophils in glandular lumen) and cryptitis
* [[Crypt (anatomy)|Crypt]] [[abscesses]] 
* Granulation tissue and reepithelialization
* [[Granulation tissue]] extending into surrounding [[submucosa]] and smooth muscle fibers.
* Submucosal fibrosis  
* [[Submucosal]] [[fibrosis]]
* Schwann cell proliferation
* [[Schwann cell]] [[proliferation]]
|}
|}
==Microscopic Pathology==


==References==
==References==

Latest revision as of 22:47, 28 December 2017

Lower gastrointestinal bleeding Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Lower gastrointestinal bleeding from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Management

Initial resuscitation
Pharmacotherapy

Surgery

Surgical Management
Endoscopic Intervention

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Guidelines for Management

Case Studies

Case #1

Lower gastrointestinal bleeding pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Lower gastrointestinal bleeding pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Lower gastrointestinal bleeding pathophysiology

CDC on Lower gastrointestinal bleeding pathophysiology

Lower gastrointestinal bleeding pathophysiology in the news

Blogs on Lower gastrointestinal bleeding pathophysiology

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for Lower gastrointestinal bleeding pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

Superior mesenteric artery and inferior mesenteric artery are the two major blood vessels that supply lower gastrointestinal tract. Disruption of blood vessel junction, formed by these two vessels, by any of the disease process results in bleeding. Diverticulosis is the most common etiology of lower GI bleeding accounting for 30% of all cases, followed by ano-rectal disease, ischemia of bowel, inflammatory bowel disease (IBD), neoplasia, and arteriovenous (AV) malformations. The characteristic gross and microscopic findings of lower gastrointestinal tracts depends upon the underlying pathology.

Pathophysiology

Blood supply

Lower GI Tract Arterial Supply Venous Drainage
Midgut
Hindgut
ɸ -Except lower rectum, which drains into the systemic circulation.
Blood supply to the intestines includes the celiac artery, superior mesenteric artery (SMA), inferior mesenteric artery (IMA), and branches of the internal iliac artery (IIA).
Source: By Anpol42 (Own work) [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons

Pathogenesis

The pathogenesis of lower gastrointestinal bleeding can be discussed based on the etiology. Diverticulosis is the most common etiology of lower GI bleeding accounting for 30% of all cases, followed by anorectal disease, ischemia, inflammatory bowel disease (IBD), neoplasia, and arteriovenous (AV) malformations.

Diagram of sigmoid diverticulum
Source:By Anpol42 (Own work) [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons
  • Anorectal disease
  • Hemorrhoids are defined as swelling and inflammation of veins in the rectal and anal region
  • Hemorrhoids can be either internal or external based on their relation to dentate line.
  • The first step in the pathogenesis of either type of hemorrhoids is weakening of the surrounding connective tissue and vein wall.[8][9][8]
  • Weakening of blood vessels can result in bleeding under pressure.
  • An anal fissure can be defined as disruption or tear in the mucosal surface of the skin.
  • During defecation, due to increased pressure which can exaggerate the tears may present as bright red rectal bleeding with severe periodic pain.[10]
  • Mesenteric ischemia results when there is inadequate blood supply at the level of the small intestine.[11][12][13][14]
  • 2 or more vessels (celiac, SMA, or IMA) must be involved for bleeding to occur.
  • Decreased blood supply can occur due to obstruction of blood vessel either by emobolus or due to vasoconstriction effect of drugs.
  • Decreased blood supply initiates necrosis of mucosal surface of intestine.
  • unopposed blood deprivation leads to trans-mural necrosis and ultimately sloughing of the tissues with associated bleeding.
  • Ischemic colitis is a condition in which injury of the large intestine results from decreased blood supply.[15][16][17]
  • The colon is most commonly involved due the presence of water shed areas ( splenic flexure and hepatic flexure).
  • Similar to mesentric ischemia bleeding occurs due to necrosis and sloughing of mucosal membrane.
  • AV Malformation/Angiodysplasia
  • In AV malformation abnormal connections occur between arteries and veins.[32][33][34][35][36]
  • This connections results in blood flow from high pressure arteries to low pressure veins without buffering effects of capillaries.
  • The lack of capillary buffers makes the vessels weak due to increased blood flow and ultimately bleeding.
  • In Angiodysplasia, with age the connective tissue of the blood vessels become weak.
  • With mild increase in pressure leads to disrupture of vessels leading to painless bleeding.

Associated Conditions

Other diseases that are commonly associated with lower gastrointestinal bleeding include:

Gross and Microscopic Pathology

Disease Gross Pathology Microscopic Pathology
Diverticulosis[37]
Angiodysplasia[38]
Hemorrhoids[8]
  • Tortuous superficial dilatations of multiple blood vessels.
Mesenteric ischemia [39]
Ischemic colitis[39]
Crohn's disease[40][41] 
Ulcerative colitis[42]

References

  1. ↑ Geboes K, Geboes KP, Maleux G (2001). "Vascular anatomy of the gastrointestinal tract". Best Pract Res Clin Gastroenterol. 15 (1): 1–14. doi:10.1053/bega.2000.0152. PMID 11355897.
  2. ↑ Granger DN, Holm L, Kvietys P (2015). "The Gastrointestinal Circulation: Physiology and Pathophysiology". Compr Physiol. 5 (3): 1541–83. doi:10.1002/cphy.c150007. PMID 26140727.
  3. ↑ "The Gastrointestinal Circulation - NCBI Bookshelf".
  4. ↑ Hobson KG, Roberts PL (2004). "Etiology and pathophysiology of diverticular disease". Clin Colon Rectal Surg. 17 (3): 147–53. doi:10.1055/s-2004-832695. PMC 2780060. PMID 20011269.
  5. ↑ Maykel JA, Opelka FG (2004). "Colonic diverticulosis and diverticular hemorrhage". Clin Colon Rectal Surg. 17 (3): 195–204. doi:10.1055/s-2004-832702. PMC 2780065. PMID 20011276.
  6. ↑ Comparato G, Pilotto A, Franzè A, Franceschi M, Di Mario F (2007). "Diverticular disease in the elderly". Dig Dis. 25 (2): 151–9. doi:10.1159/000099480. PMID 17468551.
  7. ↑ Matrana MR, Margolin DA (2009). "Epidemiology and pathophysiology of diverticular disease". Clin Colon Rectal Surg. 22 (3): 141–6. doi:10.1055/s-0029-1236157. PMC 2780269. PMID 20676256.
  8. ↑ 8.0 8.1 8.2 Lohsiriwat V (2012). "Hemorrhoids: from basic pathophysiology to clinical management". World J. Gastroenterol. 18 (17): 2009–17. doi:10.3748/wjg.v18.i17.2009. PMC 3342598. PMID 22563187.
  9. ↑ Sanchez C, Chinn BT (2011). "Hemorrhoids". Clin Colon Rectal Surg. 24 (1): 5–13. doi:10.1055/s-0031-1272818. PMC 3140328. PMID 22379400.
  10. ↑ Holland RA, Rimes AF, Comis A, Tyndale-Biscoe CH (1988). "Oxygen carriage and carbonic anhydrase activity in the blood of a marsupial, the Tammar wallaby (Macropus eugenii), during early development". Respir Physiol. 73 (1): 69–86. PMID 3140330.
  11. ↑ Krupski WC, Selzman CH, Whitehill TA (1997). "Unusual causes of mesenteric ischemia". Surg. Clin. North Am. 77 (2): 471–502. PMID 9146726.
  12. ↑ Walker TG (2009). "Mesenteric ischemia". Semin Intervent Radiol. 26 (3): 175–83. doi:10.1055/s-0029-1225662. PMC 3036494. PMID 21326562.
  13. ↑ Berland T, Oldenburg WA (2008). "Acute mesenteric ischemia". Curr Gastroenterol Rep. 10 (3): 341–6. PMID 18625147.
  14. ↑ Mastoraki A, Mastoraki S, Tziava E, Touloumi S, Krinos N, Danias N, Lazaris A, Arkadopoulos N (2016). "Mesenteric ischemia: Pathogenesis and challenging diagnostic and therapeutic modalities". World J Gastrointest Pathophysiol. 7 (1): 125–30. doi:10.4291/wjgp.v7.i1.125. PMC 4753178. PMID 26909235.
  15. ↑ FitzGerald JF, Hernandez Iii LO (2015). "Ischemic colitis". Clin Colon Rectal Surg. 28 (2): 93–8. doi:10.1055/s-0035-1549099. PMC 4442720. PMID 26034405.
  16. ↑ Theodoropoulou A, Koutroubakis IE (2008). "Ischemic colitis: clinical practice in diagnosis and treatment". World J. Gastroenterol. 14 (48): 7302–8. PMC 2778113. PMID 19109863.
  17. ↑ Rania H, Mériam S, Rym E, Hyafa R, Amine A, Najet BH, Lassad G, Mohamed TK (2014). "Ischemic colitis in five points: an update 2013". Tunis Med. 92 (5): 299–303. PMID 25504381.
  18. ↑ Kim DH, Cheon JH (2017). "Pathogenesis of Inflammatory Bowel Disease and Recent Advances in Biologic Therapies". Immune Netw. 17 (1): 25–40. doi:10.4110/in.2017.17.1.25. PMC 5334120. PMID 28261018.
  19. ↑ Hendrickson BA, Gokhale R, Cho JH (2002). "Clinical aspects and pathophysiology of inflammatory bowel disease". Clin. Microbiol. Rev. 15 (1): 79–94. PMC 118061. PMID 11781268.
  20. ↑ Woźniak-Parnowska W, Werakso B (1974). "[Comparative studies of microbiological purity of ointments by the direct culture method and use of membrane filters]". Acta Pol Pharm (in Polish). 31 (6): 819–23. PMID 4447044.
  21. ↑ Mazal J (2014). "Crohn disease: pathophysiology, diagnosis, and treatment". Radiol Technol. 85 (3): 297–316, quiz 317–20. PMID 24395894.
  22. ↑ Jewell DP (1989). "Aetiology and pathogenesis of ulcerative colitis and Crohn's disease". Postgrad Med J. 65 (768): 718–9. PMC 2429831. PMID 2694136.
  23. ↑ 23.0 23.1 Sartor RB (2006). "Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis". Nat Clin Pract Gastroenterol Hepatol. 3 (7): 390–407. doi:10.1038/ncpgasthep0528. PMID 16819502.
  24. ↑ Head K, Jurenka JS (2004). "Inflammatory bowel disease. Part II: Crohn's disease--pathophysiology and conventional and alternative treatment options". Altern Med Rev. 9 (4): 360–401. PMID 15656711.
  25. ↑ Zhang YZ, Li YY (2014). "Inflammatory bowel disease: pathogenesis". World J. Gastroenterol. 20 (1): 91–9. doi:10.3748/wjg.v20.i1.91. PMC 3886036. PMID 24415861.
  26. ↑ Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF (2017). "Ulcerative colitis". Lancet. 389 (10080): 1756–1770. doi:10.1016/S0140-6736(16)32126-2. PMID 27914657.
  27. ↑ Farrell RJ, Peppercorn MA (2002). "Ulcerative colitis". Lancet. 359 (9303): 331–40. doi:10.1016/S0140-6736(02)07499-8. PMID 11830216.
  28. ↑ Rönnblom LE, Janson ET, Perers A, Oberg KE, Alm GV (1992). "Characterization of anti-interferon-alpha antibodies appearing during recombinant interferon-alpha 2a treatment". Clin. Exp. Immunol. 89 (3): 330–5. PMC 1554468. PMID 1516252.
  29. ↑ Itzkowitz S (2003). "Colon carcinogenesis in inflammatory bowel disease: applying molecular genetics to clinical practice". J. Clin. Gastroenterol. 36 (5 Suppl): S70–4, discussion S94–6. PMID 12702969.
  30. ↑ Ullman TA, Itzkowitz SH (2011). "Intestinal inflammation and cancer". Gastroenterology. 140 (6): 1807–16. doi:10.1053/j.gastro.2011.01.057. PMID 21530747.
  31. ↑ Kraus S, Arber N (2009). "Inflammation and colorectal cancer". Curr Opin Pharmacol. 9 (4): 405–10. doi:10.1016/j.coph.2009.06.006. PMID 19589728.
  32. ↑ Foutch PG (1993). "Angiodysplasia of the gastrointestinal tract". Am. J. Gastroenterol. 88 (6): 807–18. PMID 8389094.
  33. ↑ Dodda G, Trotman BW (1997). "Gastrointestinal angiodysplasia". J Assoc Acad Minor Phys. 8 (1): 16–9. PMID 9048468.
  34. ↑ Kheterpal S (1991). "Angiodysplasia: a review". J R Soc Med. 84 (10): 615–8. PMC 1295562. PMID 1744847.
  35. ↑ Athanasoulis CA, Galdabini JJ, Waltman AC, Novelline RA, Greenfield AJ, Ezpeleta ML (1977). "Angiodysplasia of the colon: a cause of rectal bleeding". Cardiovasc Radiol. 1 (1): 3–13. PMID 311247.
  36. ↑ Sami SS, Al-Araji SA, Ragunath K (2014). "Review article: gastrointestinal angiodysplasia - pathogenesis, diagnosis and management". Aliment. Pharmacol. Ther. 39 (1): 15–34. doi:10.1111/apt.12527. PMID 24138285.
  37. ↑ West AB, Losada M (2004). "The pathology of diverticulosis coli". J. Clin. Gastroenterol. 38 (5 Suppl 1): S11–6. PMID 15115923.
  38. ↑ Stamm B, Heer M, Bühler H, Ammann R (1985). "Mucosal biopsy of vascular ectasia (angiodysplasia) of the large bowel detected during routine colonoscopic examination". Histopathology. 9 (6): 639–46. PMID 4029903.
  39. ↑ 39.0 39.1 Mitsudo S, Brandt LJ (1992). "Pathology of intestinal ischemia". Surg. Clin. North Am. 72 (1): 43–63. PMID 1731389.
  40. ↑ Price AB, Morson BC (1975). "Inflammatory bowel disease: the surgical pathology of Crohn's disease and ulcerative colitis". Hum. Pathol. 6 (1): 7–29. PMID 1089084.
  41. ↑ Wright CL, Riddell RH (1998). "Histology of the stomach and duodenum in Crohn's disease". Am. J. Surg. Pathol. 22 (4): 383–90. PMID 9537465.
  42. ↑ DeRoche TC, Xiao SY, Liu X (2014). "Histological evaluation in ulcerative colitis". Gastroenterol Rep (Oxf). 2 (3): 178–92. doi:10.1093/gastro/gou031. PMC 4124271. PMID 24942757.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Lower_gastrointestinal_bleeding_pathophysiology&oldid=1425998"