TISSUE PATHOLOGY - Essay Example

?TISSUE PATHOLOGY DISSERTATION 0 of the disease 1 Introduction The body’s defenses against diseases are in place in the form of the immune system and this system, made up of several components and functions is supposed to ensure that as much as possible, the body is protected from any form of diseases or at worse, the body will be in a position to fight diseases that attack the body to ensure healing (Lichtenstein, Hanauer and Sandborn, 2009). These defensive mechanisms notwithstanding, it has not been always been the case that the body has been protected against diseases. There are many forms of diseases that attack the body in various ways and bring different effects. Once there is a failed system through the natural functioning of the immune system, doctors and pharmacists try to intervene through diagnosis and pharmacology (Annunziata et al, 2012). It is important to state however that in order for the roles of the medical professionals to be successful, an important component of the disease they have to consider is the pathology of the disease. This paper is therefore dedicated to finding the pathologic processes involved in the disease of Crohns Disease. 1.2 What is Crohns Disease? Crohns disease is one of the inflammatory bowel diseases that mainly affect the gastrointestinal tract of a person (Hutchinson et al, 1994). There are other known inflammatory bowel diseases but in the case of Crohns disease, the target of infection has often been the gastrointestinal area from the mouth to the anus and comes with several imploratory symptoms. Due to the fact that there may be other diseases with similar description as the Crohns disease, it is very important that the forthcoming symptoms of the disease are critically examined to be sure if it is really Crohns disease. Symptoms such as diarrhea, abdominal pain, weight loss and vomiting, with some outward symptomatic complications outside of the gastrointestinal including arthritis, tiredness and skin rashes should commonly be looked out for (Levesque et al, 2010). Because of the target area of the disease, it has often been called the regional enteritis, referring to the fact that gastrointestinal (GI) tract with common emphasis on the end part of the small intestine is the worse target point. In the figure below, the specific organ within the human system that Crohns disease attacks, making it have the name of regional enteritis is exhibited. Fig. 1 Gastrointestinal Tract Source: National Institute of Diabetes and Digestive and Kidney Diseases 1.3 Who gets Crohns Disease? Medically, Crohns disease presents a perfect case of what may be called no respecter of persons as it affects men equally as it affects women. Both men and women may therefore get Crohns disease on the same probability basis. The disease has also been recorded in almost people of every age group. These factors notwithstanding, Sauer and Kugathasan (2009) notes that there are high risk factors with the commonest being biological relations. That is, the disease is commonly found in people who may be biological siblings and also possessing the same form of IBD. In terms of age also, there is high risk for people between the ages of 13 to 30 to contract Crohns disease, as well as high risk for people who smoke, be they men or women. Along the lines of race, Afircan Americans have reduced risk to getting Crohns disease as opposed to people of Jewish descent who have higher risk of getting Crohns disease (Bernstein et al, 2001). Due to the fact that there is no exclusive population as far as who may get the disease is concerned, adherence to preventive schemes and regular medical checkups following any of the symptoms mentioned earlier is the best way to stay out of trouble with the disease. 2.0 Description of the pathological process 2.1 Etiology 2.11Genetic Genetically, there is what may be called a polygenic basis for Crohns disease (Solem et al, 2004). This is because whereas Classic Mendelian inheritance is not seen as a predisposition for the disease, people who are first-degree relatives have been found to exhibit up to 13 to 18% increase in incidence with Crohns disease (Farmer, Michener and Mortimer, 1980). Furthermore, twins have a clear cut 50% concordance rate with the disease. Through a molecular linkage analysis of the disease, it has been found that most affected families possess nucleotide-binding domain 2 (NOD2) as a vulnerability gene reflecting in Crohns disease (Satsangi, Parkes and Jewell, 1998). The genetic place of NOD2 with Crohns disease is that it activates nuclear factor-kappa B also known as NF-kB through the binding of intracellular peptidoglycans with proteins encoded in the NOD2. Once this is achieved, there is the total blockade of excessive immune activation, rendering the role of the immune system in subverting disease causing pathogens useless. Worse of all, there is a combat on luminal microbes once the activation of NF-kB is executed. It is however good to know that people carrying NOD2 mutations who get Crohns disease are less than 10% of the population of affected people. There is also a linkage with multiple chromosomes such as 3, 7, 12 and 16 through genomic screening (Irving , Pasi and Rampton, 2005). 2.12 Environmental Information on the environmental risk factors associated with Crohns disease is limited. It is however known that there are some levels environmental factors causing the disease. Generally, an environmental factor may be described as a causative agent that arises outside of the body’s own immune and genetic mechanisms (Spina et al, 2005). In this direction, smoking of cigarette has been outlined as a major environmental risk factor with cigarette smokers having twice the likelihood of getting Crohns disease as non cigarette smokers. Even with the case of smoking, there is very little evidence as to the contribution of cigarette smoking to the pathogenesis of the disease even though research shows higher risk rate for cigarette smoker. Another indicator of environmental association with the disease is the fact that incidence of the disease has suddenly gone up in places that are fast becoming industrialized (Persson et al, 1994). But still, there is no evidence based study to give the most outlining reasons this situation is so. But to further classify environmental factors as those that do not have direct relation with the immunology of the patient or the genetics of the patient, it could be said that the use of oral contraceptives, which cause thrombi in the long run and history with inflammation of the appendix could commonly expose the gut to Crohns disease (Karlen et al, 1999). 2.13 Immunological and epithelial damage There are clear evidences to support the assertion that the immune system is involved in the development Crohns disease. The first evidence is in the fact that there are immunosuppressive drugs that perfectly treat Crohns disease. The second evidence is in the fact that Crohns disease results in and brings about systemic immune problems (Palli et al, 2000). Under strict clinical checks, it will be noted that patients who suffer Crohns disease have changes to their CD4+ cells, which is a critical component of the immune system, suggesting that the immune system is indeed involved in Crohns disease (Loftus et al, 2000). Crohns disease has also been noted to come with a number of epithelial defects which includes but not limited to tight junction barrier function, extracellular matrix barrier proteins and Paneth cell antibacterial peptide (Day et al, 2003). Modern research and studies show that T-helper cell type 17 may also be a contributing factor to the pathogenesis of Crohns disease as it is already established that T-helper cell type 1 remains a recognized feature in the disease (Bernstein et al, 2001). Conclusively, IL-23 receptor polymorphisms have been identified as useful components within the immune system that have a dedicated role of conferring protection from Crohns disease (Bernstein et al, 2001). 2.2 mechanisms of development (pathogenesis) Regardless of the general and commonly pointed to symptoms and complications associated with Crohns disease, there exist some key differential mechanisms of developments. First of these, which are directly related to the pathogenesis of the Crohns disease are identified. These five are briefly discussed below. Ileocolitis: This form of Crohns disease affects the ileum and colon and thus its name, Ileocolitis. Ileocolitis happens to be one of the commonest ways in which Crohns disease manifests its self as it causes very painful cramping and abdominal disorder (Solem et al, 2004). Often times, there is severe experience of loss of weight associated with infection. Ileitis: From the structure of its name, it would be noted that Ileitis only associates itself with the ileum and thus happens to be the form of Crohns disease that affects the ileum only. Though there are several symptomatic similarities with the other mechanisms of development such as Ileocolitis, there is a major difference in symptomatic display and this takes place with the presence of fistulas, otherwise known as inflammatory abscesses, which forms in the right lower quadrant of the abdomen (Cline, 2012). Gastroduodenal Crohn’s Disease: This form of Crohns disease is quite away from the ileum as it affects the stomach and the duodenum sections of the digestive system. As part of the gastrointestinal tract, it would be said that gastroduodenal Crohns disease affects the first part of the small intestine and leaves patients with symptoms including nausea and weight loss, arising from loss of appetite. Once there is the onset of vomiting, it is an indication that stricture has developed with narrowed segments of the bowel, which have become obstructed (Cline, 2012). Jejunoileitis: Upon infection, this will lead to the patching of the jejunum in the form of inflammations. Jejunoileitis could be said to be the opposite of gastroduodenal Crohns disease because this type affects the upper half of the small intestine whiles the latter affects the first part of the small intestine (Annunziata et al, 2012). Once affected, there could be various levels of abdominal pain from mild to severe. Fistulas are possible but not very rampant of reported cases. Diarrheas may also set in as patients often experience cramps after meals. Granulomatous Colitis: This is a kind of Crohns disease that affects just the colon and no other part of the digestive system. Fistulas, ulcers and abscesses occurring around the anus is common as well as rectal bleeding and diarrhea, all coming up as symptoms of the disease. 3. Relevance of the pathology under consideration to the 3.1 Relevance of pathology on aetiology The pathology of Crohn’s disease discussed so far gives so much relevance and relating significance to the aetiology of the disease. In the first place, it has been realized that there is so much genetic relationship with the cause of Crohn’s disease, implying that among people who are siblings or genetically related, a preventive approach could be used in the control of the disease. Secondly, the immunological and epithelial damage associated with the disease call for more medical research that are aimed at correcting some of the wrongs and disorders either surgically or by the introduction of corrective drugs. Finally, the environmental causes of the disease gives a sense of environmental awareness that is built around the need to avoiding contact and interaction with certain harmful substances that have been identified to be potential in bringing about the disease. In all, the relevance of the pathology on aetiology is in the identification and description of treatment and control needed to combat or battle the disease. It also predicts the extent of seriousness needed to be attached to the giving of care to affected persons. 3.2 progression and severity of the disease As patients live with crohn’s disease for a while, it gets to a time that the disease progresses in severity, creating a chronic and indolent course which is associated with relapse and remit in the long while. Interestingly, these instances of progression and severity happens regardless of the part of the body that the disease affects. Generally though, it is the ileum that suffers worse as shown in the pictures below Fig. 2 A Healthy Ileum Source: Rendi (2011) Fig. 2 Ileum of a patient with Crohn’s disease Source: Rendi (2011) In the following sub-sections, three of the cases of severity in crohn’s disease are done. 3.21 Fissures, fistulas, and abscesses Inflammations that are identified to be transmural and chronic could bring about fissures, which will commonly be found at the bowel wall. Once this is also neglected for a while, fistulas and abscesses set in. unlike fissures, the fistulas actually have the potential of developing not just in the bowel wall but also between other organs and the bowel wall. This is what results in varying types and forms of fistulas such as entrevaginal fistulas and enterovesical fistulas. The effects of these developments includes but not limited to feculent vomiting, urinary tract infections, and feculent soiling of skin lesions (Palli et al, 2000). As outlined in the relevance of pathology to aetiology, it will be seen that fistulas are very common for postsurgical patients, a reason of which medical interventions are always prescribed whenever necessary. 3.22 Obstruction In chronic situations, prolonged crohn’s disease would cause various forms of obstruction for patients; even though undergoing medical interventions (Karlen et al, 1999). In one study, it was said that the experiences with obstruction are often opposite with experiences with fissures, fistulas and abscesses (Karlen et al, 1999). This means that patients who would experience the former could normally not experience the latter. Technically, obstruction takes many different forms with symptoms such as cramping, postprandial bloating resulting from presence of edema in the walls of the bowel, and borborygmus (Rendi, 2011). Obstruction also occurs in cases where there is a thickening of the bowel wall with resulting narrowing of the lumen. The resultant symptom or effect of this is constipation and obstipation. In worst case scenarios, there will be the formation of stricture and further thickening of the bowel wall, bringing about complete obstruction. 3.23 Extraintestinal involvement Progression and severity could interestingly go beyond the intestinal region with extraintestinal involvements. It has been found that other than the intestinal region, there are some areas outside of the intestine that suffers repercussions and effects of prolonged crohn’s disease. Some of these areas are the anus, mouth, eyes, skin, liver, joints and bile ducts (Rendi, 2011). With the mouth, aphthoid ulcers and erosions are common while the anus may be infected with fissures with the stomach experiencing ulceration. In his research, Burgdorf (1981) stated that Uveitis, episcleritis, pyoderma gangrenosum and constitutional eczema are all cases of severity of crohn’s disease. 3.3 Clinical manifestations There are key changes which when noticed in a person should be a cause of alarm for checking for or against crohn’s disease. Apart from the need to check for the presence of crohn’s disease, it has been noted that many are those who mistake other forms of inflammatory diseases for crohn’s disease and therefore need professional diagnosis to be sure whether or not come of these clinical manifestations are really signs of crohn’s disease. The first form of clinical manifestation is fatigue, which occurs for many years; normally with the presence of such prolonged diarrhea. Weight loss and prolonged fevers are all indicative factors. But of all the signs and symptoms, abdominal pain and diarrhea may stand out for closer clinical attention and diagnosis. From fig. 1, it can be seen that crohn’s disease affects all of the gastrointestinal tract moving from the mouth to the perianal area. However, it is common that the most forms of clinical manifestations would take place within the gastrointestinal region with abdominal pain resulting. Crampy abdominal pain would manifest no matter the disease distribution. Quadrant pain comes about as fibrotic strictures develop from continuous sequence and records of small bowel and obstruction. It is also common that no clinical manifestations will show up until constipation and obstructions resulting from luminal narrowing takes place with abdominal pain (Levesque et al, 2010). With diarrhea, the rate of experience may not be as common as may be seen with abdominal pain as there may be flatuations with time in the levels of severity. Commonly, the type of diarrhea that should call or diagnosis is the prolonged type that does not come with bleeding but with signs of other inflammatory bowel diseases (Annunziata et al, 2012). 3.4 Morphologic changes There have been current ultrstructural scans that have indicated that there are early epithelial lesion associated with crohn’s disease with no known morphological patterns (Schattenfroh, Bartels and Nagel, 1994). This notwithstanding, within the lamina proprai, submucosa and deeper layers of the affected areas, there is likelihood to be increase in plasma cells, lymphocytes, eosinophilic and nuetrophilic granulocytes and accompanying focal edema and inflammation of tissue (Schattenfroh, Bartels and Nagel, 1994). Comparative to known and orginal structural formations of key cells like absorptive cells, goblet cells, paneth cells and M cells, significant alterations depicting injury may be seen under unltrastructural observations. 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