Pathophysiology

PATHOPHYSIOLOGY

Therole of genetics and immunology in the pathophysiology of Crohnsdisease

Genetics and immunology have amajor role to play in its pathophysiology of Crohn’s Disease. Forinstance, people who have low levels of immunity are more susceptibleto contracting this illness, especially when they are exposed toenvironments that have infectious elements (Hirschfield, &ampGershwin, 2013). As this disease continues to develop, there is thechance that the immune system of the body could turn out and startattacking some cells and tissues in the body, thereby causingautoimmune reactions (Brant, 2013).

There is a huge relationshipbetween Crohn’s disease and genetic variation in autophagy gene andNOD2. It is also brought about by defects in the genes that encodeinterleukin-23 and interleukin 12B. As a result, these lead to thedecrease in the activation of nuclear factor (NF)-KB. This may alsoprevent excessive activation of immunity as well as the capability ofthe NOD2 to combat luminal microbes (Blaser, Bork, Fraser, Knight, &ampWang, 2013). The effect of defects in the NOD2 is, however, not veryenhanced, given the fact that less than 10% of people who have somemutations in NOD2 go ahead to develop this disease. There are alsoother genes that are paramount as far as this disease is concerned.They include autophagy-related 16-like (ATG 16L 1) andimmunity-related GTPase M (IRGM). These genes are mostly involved inthe clearance of bacteria that are found inside cells and autophagy.

Thepathophysiological mechanism causing the formation of Crohn’sDisease fistulas

Excessive inflammation of theintestines could lead to the scarring of the inner walls of theintestines. These lead to the development of cancers (Scharl, &ampRogler, 2014). These ulcers could develop into tunnels that could runstraight from the digestive system to other systems in the body.These tunnels are referred to as fistulas. While at most times smallfistulas may not have great harm, larger ones are often associatedwith a number of problems (Goldberg, &amp Tawadros, 2014). One ofthe problems lies in the fact that they could lead to the developmentof great pain on the person having the disease. They could also leadto high temperatures on the person as well as continuous leaking ofmucus or stools. In most cases, the stool normally contains sometraces of blood.

HowCrohn’s disease can progress to intestinal cancer

Crohn’s disease is highlyassociated with the development of colorectal cancer (Kostic, Xavier,&amp Gevers, 2014). This is because the constant inflammation of theintestinal walls makes the cells of these organs develops a mechanismthat tries to abate the situation (Rieder, Zimmermann, Remzi, &ampSandborn, 2013). These are normally referred to as non-necrotizinggranulomas. The granulomas are normally associated with a high levelof cell division. Given the fact that this disease is also associatedwith people who are immune and genetically challenged, there is highchance that the continuous growth of the granulomas could continue,thereby turning into malignant or systemic cancers (Rubin, Shaker, &ampLevin, 2012).

Thepathophysiology of cobblestone appearance of the intestinal lining

The lesions and inflammations ofthe inner linings of the intestines could result in some sectionsbeing ulcerated. This is especially where little action is taken toaddress the problem and, thereby, the inner linings of the intestinescontinue to swell (Iida, Yamashita, Arimura, &amp Shinomura, 2016).These ulcerations and inflammation are not uniform and could bedotted all along the various areas along the inner walls of theintestines. When an endoscopy is conducted upon an individual whoappears to have Crohn’s disease, there is a chance that a‘cobblestone’ appearance will be noted on the inner walls of theintestines as shown by the intermittent lesions found in the liningof those walls. (Lim, Moon, Park, Park, Kim, Kim, &amp Lee, 2013).

References

Blaser, M., Bork, P., Fraser, C.,Knight, R., &amp Wang, J. (2013). The microbiome explored: recentinsights and future challenges.&nbspNatureReviews Microbiology,&nbsp11(3),213-217.

Brant, S. R. (2013). Promises,delivery, and challenges of inflammatory bowel disease risk genediscovery.&nbspClinicalGastroenterology and Hepatology,&nbsp11(1),22-26.

Goldberg,S. M., &amp Tawadros, P. S. (2014). Anal Sepsis: Anatomy,, and Presentation. In&nbspAnus&nbsp(pp.221-229). Springer London.

Hayashi, T., Schönfeld, C., &ampTsokos, M. (2013). “Cobblestone” appearance of the ascendingcolon.&nbspForensicscience, medicine, and pathology,1-3.

Hirschfield, G. M., &amp Gershwin,M. E. (2013). The immunobiology and pathophysiology of primarybiliary cirrhosis.&nbspAnnualreview of pathology: Mechanisms of disease,&nbsp8,303-330.

Iida, T., Yamashita, K., Arimura,Y., &amp Shinomura, Y. (2016). Colonic Sarcoidosis Presenting asGranulomatous Appendicitis.&nbspJournalof gastrointestinal and liver diseases: JGLD,&nbsp25(1),8-8.

Kostic, A. D., Xavier, R. J., &ampGevers, D. (2014). The microbiome in inflammatory bowel disease:current status and the future ahead.Gastroenterology,&nbsp146(6),1489-1499.

Lim, C. S., Moon, W., Park, S. J.,Park, M. I., Kim, H. H., Kim, J. B., … &amp Lee, S. H. (2013). ARare Case of Free Bowel Perforation Associated with InfliximabTreatment for Stricturing Crohn`s Disease.&nbspTheKorean Journal of Gastroenterology,&nbsp62(3),169-173.

Rieder, F., Zimmermann, E. M.,Remzi, F. H., &amp Sandborn, W. J. (2013). Crohn`s diseasecomplicated by strictures: a systematic review.&nbspGut,gutjnl-2012.

Rubin, D. C., Shaker, A., &ampLevin, M. S. (2012). Chronic intestinal inflammation: inflammatorybowel disease and colitis-associated colon cancer.&nbspFrontiersin immunology,&nbsp3,107.

Scharl, M.,Bruckner, R. S., &amp Rogler, G. (2016). The two sides of the coin:Similarities and differences in the pathomechanisms of fistulas andstricture formations in irritable bowel disease.&nbspUnitedEuropean Gastroenterology Journal,2050640616635957.

Scharl, M., &amp Rogler, G.(2014). of fistula formation in Crohn’sdisease.&nbspWorld JGastrointest Pathophysiol,&nbsp5(3),205-212.