Symptoms Of Gastrointestinal Inflammatory Diseases Health And Social Care Essay

Symptoms Of Gastrointestinal Inflammatory Diseases Health And Social Care Essay Inflammation is a type of defence mechanism that the body exhibits in response to damage to part or all of its tissues. Depending on the severity of the insult and consequent damage to cells, the inflammatory response involves recruitment of varying proportions of neutrophils, eosinophils, basophils, lymphocytes (both T and B cells), natural killer cells and cells of the monocyte macrophage lineage. Inflammation normally seeks to eliminate the cause of the insult and repair the damage caused. However, if the damage persists, persistent recruitment of inflammatory cells to the injured area will lead to further damage leading to chronic inflammation. [9] The gastrointestinal (GI) tract is a hollow muscular tube running from the mouth to the anus. It is about 7 to 9 meters long in adult. The enormous mucosal surface, which is the innermost layer of the gastrointestinal tract, is constantly exposed to a plethora of antigenic, mitogenic, mutagenic, and toxic stimuli thus clearly making th e gastrointestinal tract vulnerable to such inflammatory responses. [10] Gastrointestinal inflammatory diseases Inflammation can affect any part of the gastrointestinal tract. Inflammatory Bowel Disease The inflammatory bowel diseases (IBD) are chronic inflammatory diseases affecting the gastrointestinal tract. IBD encompasses two forms of intestinal inflammation, namely ulcerative colitis and Crohns disease. Crohns Disease may affect all parts of the gastrointestinal tract, but more commonly it involves the distal part of the small intestine and the colon. On the other hand, ulcerative colitis results in colonic inflammation which can affect only the rectum, or can progress proximally to involve the colon, either partly or entirely [11]. Currently, the etiology of IBD is unknown, but recent investigations have identified contribution of genetic, environmental as well as immunological factors underlying the disease [12]. Susceptibility to disease is thereby determined by genes encoding immune responses which are triggered by environmental stimuli [13]. Figure 1.1 shows a combination of genetic and environmental culprits triggering activation of intestinal immune and non-immune syste ms which culminate in inflammation and tissue damage. [14] Figure 1.1: Etiology and pathogenesis of IBD. Current medical therapy of IBD consists of salicylates, corticosteroids, immunosuppressants and immunomodulators. However, their use is associated with severe side effects and complications, such as an increased rate of malignancies or infectious diseases. [15] Gastritis (Inflammation of stomach lining) Gastritis represents a group of disorders characterized by gastric epithelial cell injury and regeneration together with the induction of inflammatory changes in the gastric mucosa [16]. Inflammation of the gastric mucosa occurs as a result of an imbalance between mucosal defensive and aggressive factors. It is now well established that H. pylori infection is the cause of the most common form of chronic gastritis [17]. Studies have established that H.pylori directly contributes to abundant inflammatory response and cause injury to gastric epithelial cells through elaboration of cytotoxic factors and it may also make gastric epithelial cells more susceptible to carcinogenic conversion [18]. There is also evidence that drugs and alcohol may cause gastritis. Iron therapy has also been implicated as a cause of gastritis. Iron-pill gastritis involves mucosal erosion which is accompanied by acute and chronic inflammation and marked regenerative epithelial changes [19]. Autoimmune and hype rsensitivity reactions may also be culprits in gastritis. [20] Esophagitis (Inflammation of the oesophagus) Eosinophilic esophagitis is a chronic inflammatory condition whereby presence of dense eosinophilic inflammation of esophageal mucosa contributes to esophageal dysfunction. Eosinophilic esophagitis is a newly acknowledged disease whose incidence and prevalence is rapidly increasing in developed and developing countries [21]. The disease is a major cause of gastrointestinal morbidity among children and adults. It is thought to be immune mediated, whereby food or environmental antigens trigger a T-helper (Th)-2 inflammatory response. [22] Pancreatitis Chronic pancreatitis is well-known as a persistent inflammatory disorder of the pancreas, characterized by destruction of the pancreatic parenchyma, maldigestion, chronic pain and diabetes mellitus. Susceptibility to chronic pancreatitis is inherited in a complex manner, involving mutations in several genes conferring various degrees of risk. [23] Although the exact etiology of acute and chronic pancreatitis is unknown, studies have revealed that they are most frequently caused by a high consumption of alcohol and tobacco [24]. Other common causes include gallstones, hypertriglyceridemia, hyperparathyroidism, trauma, pancreatic tumors, and intra-abdominal and non-abdominal surgery. Drugs constitute a relatively infrequent cause of acute pancreatitis and account for 1.4 to 2% of the cases in the general population. [25] Gastroenteritis Gastroenteritis refers to inflammation of the gastrointestinal tract, involving the stomach and intestines. Acute gastroenteritis is a common disease occurring worldwide, which affects all age groups and leading to an estimated three million deaths annually. In many patients the causal agent cannot be identified, but research has implicated bacteria and parasites as well as viruses such as rotavirus, adenovirus, and caliciviruses as major culprits in causing gastroenteritis. [26] Symptoms of gastrointestinal inflammatory diseases Table 1.1: Symptoms of GI inflammation Gastrointestinal Inflammatory Disease Symptoms Inflammatory Bowel Diseases Diarrhoea Blood in stools Gastrointestinal bleeding Abdominal pain Fistulas (usually around the rectal area, may cause draining of pus, mucus, or stools) Constipation Weight loss [11] Gastritis Nausea Vomiting (possibly with blood) Abdominal pain and bloating Indigestion Loss of appetite Blood in the stools. [27] Esophagitis Food impactions Dysphagia (difficulty swallowing) Nausea Vomiting Heartburn chest pain or abdominal pain [28] Pancreatitis Abdominal pain Nausea Vomiting Weight loss Mild yellowing of skin (jaundice) Fatty stools [29] Gastroenteritis Abdominal pain Nausea and vomiting Diarrhoea Joint stiffness or muscle pain Poor feeding and weight loss [30] Biomarkers of Gastrointestinal inflammation Inflammatory activities occurring within the gastrointestinal tract can be assessed using a variety of techniques. Presently, the most reliable means to assess intestinal inflammation is endoscopy with mucosal biopsy. However, this technique is expensive, invasive, time-consuming and is not popular with patients [31]. Moreover, this technique requires a skilled operator and an uncomfortable preparatory regimen. Other techniques constitute measurement of conventional non-invasive acute-phase inflammatory markers in plasma and faeces. [32] Blood inflammatory biomarkers Serological biomarkers are principally produced when the intestine is exposed to the normal commensal bacteria and their increased levels might be indicative of an impaired or wrongly regulated inflammatory response. Erythrocyte sedimentation rate (ESR), white blood cell count (WBC) and C-reactive protein (CRP) are well-established indicators of inflammatory conditions within the intestine. [33] C-reactive protein (CRP) CRP is one of the vital acute phase proteins in humans, which is normally produced in low quantities by hepatocytes (/= 30 kg/m2. However, this method has been subjected to criticism because it does not distinguish fat from fat-free mass such as muscle and bone [76]. In addition, it has also been observed that for the same value of BMI, women are, on average, fatter than men, and Asians are, on average, fatter than Caucasians [77]. Distribution of body fat is highly important in evaluating obesity-related health risks. It has been well-established that accumulation of intra-abdominal fat, that is central obesity, shows stronger correlation with disease states in comparison with total body fat [78]. According to a recent study, waist circumference, and not BMI, explains obesity-related health risk. [79] Obesity is associated with low-grade inflammation. The inflammatory process originates and resides mainly in adipose tissue, as it is responsible for production and secretion of various proteins involved in development of obesity related adverse health effects [80] . Through this mechanism, increasing obesity leads to reduction of adiponectin levels, which has anti-inflammatory properties, and to elevated levels of C-reactive protein (CRP) and results in systemic inflammation, including gastrointestinal inflammations. Intestinal inflammation is a key feature in severe obesity [81]. A study has established diet-induced intestinal inflammation as an early biomarker and mediator of obesity [82]. Findings in adult humans and in animals have suggested that the inflammatory status at mucosal surfaces of various organs including the adipose tissue, ooesophagus, pancreas, colon, which are associated with the increase of fat mass, may be involved in the pathogenetic pathways of obesity compli cations [81]. In addition, animal studies showed that obese mice display enhanced intestinal permeability [83]. Recent epidemiological studies have demonstrated that obesity is associated functional bowel disorders, which may have resulted from a low-grade inflammation [81]. Furthermore, obesity has been found to increase the severity of acute pancreatitis through amplification of the immune response to injury [84]. Obesity, especially abdominal obesity, was also found to be a significant risk factor for erosive esophagitis [85]. Very recently, an association of obesity with endoscopic gastritis was demonstrated. [86] Results of a recent study pointed that circulating neutrophils are greatly activated in severely obese subjects, thereby indicating the association between obesity and activation of the innate immune response. In addition, elevated levels of faecal calprotectin, which is a non-invasive biomarker of intestinal inflammation, have been reported in individuals with high BMI [87]. Another study demonstrated a strong correlation between circulating calprotectin levels with abdominal adiposity in Japanese men, and also showed that weight loss in the subjects led to decreased circulating calprotectin. [88] Genetics Gastrointestinal inflammatory diseases may also be influenced by genetic components. Family studies have revealed strong familial association and high sibling risk ratio in etiology of eosinophilic esophagitis. [89] Genetic factors also play a role in pancreatitis. [90] In addition, increased familial risk has also revealed a genetic basis in Inflammatory Bowel Disease [91], and an increased faecal calprotectin concentration has also been demonstrated in asymptomatic first-degree relatives of IBD patients, thus indicating a high prevalence of subclinical intestinal inflammation in them. [92] Gender Gender may play a role in gastrointestinal inflammatory diseases. Animal studies in mice have demonstrated  that females  develop more severe intestinal inflammation than do males [93]. On the other hand, a study has shown that bile reflux gastritis was more frequent to male gender [94]. Another study found a positive correlation between the male sex and pancreatitis [95]. Additional studies found that there is a slight preponderance of colitis ulcerosa in men and of Crohns disease in women [96]. Lifestyle factors Smoking Cigarette smoking affects ulcerative colitis (UC) and Crohns disease (CD) in very different ways. According to recent studies, smoking cigarettes has a negative effect on the course of CD, and that smoking cigarettes may have a protective effect in some patients with UC [97]. Conversely, smoking cessation aggravates ulcerative colitis and improves CD [98]. Furthermore, studies showed that smoking conferred a strong, independent and dose-dependent risk of pancreatitis that may be additive or multiplicative when combined with alcohol. [99]. Alcohol Most cases of chronic pancreatitis are alcohol-related. [100] However, a recent study showed that faecal calprotectin concentrations in active-drinking alcoholics were not significantly different from the healthy controls thereby indicating the absence of a subclinical intestinal inflammation involving activation of neutrophils in the alcoholics. [101] Diet Pro- or prebiotics will directly influence the microbial flora, while immunonutrition, including omega-3 fatty acids and certain polyphenols, including green tea polyphenols, may reduce the symptoms of gut inflammation [102]. Studies have shown that lycopene, an antioxidant which is abundantly found in foods that have a natural red color such as tomato and watermelon, may play a role in attenuating the inflammatory process [103]. A study showed that intestinal bacteria and high fat diet interact to promote proinflammatory changes in the small intestine [104]. Certain studies suggested that refined sugar consumption might be a risk factor for Crohns Disease, but not Ulcerative Colitis. Fat intake is reportedly positively associated with ulcerative colitis [105], whereas vegetables and fiber consumption seem to decrease GI inflammatory process as shown by decreased faecal calprotectin [106]. Stress Psychological stress reportedly increases disease activity in inflammatory bowel disease by both direct and indirect mechanisms as shown below. [107] Figure 1.2: Direct and indirect ways by which stress can aggravate Inflammatory Bowel Diseases Socioeconomic status Epidemiological studies have demonstrated Inflammatory Bowel Diseases to be more prevalent among people of high socioeconomic status. Such an occurrence was explained by the hyegiene hypothesis, according to which individuals with higher standards of living may be living in cleaner environments and thus are more protected from childhood infections, but however exposure to infectious agents later in life makes them more vulnerable to chronic intestinal inflammation in adulthood [108]. A study in China demonstrated that levels of faecal calprotectin were significantly increased in the rural infants as compared to urban ones. [5] Gastric surgery Partial gastrectomy increases the risk for chronic pancreatitis in male alcoholics [109]. Appendectomy has possibly protective effects in ulcerative colitis but it is suggested as a risk factor in Crohns disease. Tonsillectomy is a risk factor for developing Crohns disease. [110]