Inflammatory Bowel Disease - A Holistic Perspective
A large population of macrophages reside in the normal intestinal mucosa where they represent a major APC population. Various studies suggest that intestinal macrophages cannot easily be induced to mediate acute inflammatory responses. In inflammatory bowel disease, however, there is an increase in the mucosal macrophage population where the recruited macrophages are phenotypically disparate from the resident macrophages (Mahida, 2000). These recruited macrophages appear to perform a major role in mediating the chronic mucosal inflammation seen in patients with ulcerative colitis and Crohn's disease. There is evidence that the recruited macrophages release reactive metabolites of oxygen and nitrogen and proteases which degrade the extracellular matrix. There is also evidence that the recruited macrophages may be primarily responsible for the secretion of cytokines which are important in the pro-inflammatory process, including TNF-a, IL-1, IL-6, IL-8, IL-12 and IL-18.
Crohn's disease and ulcerative colitis are the two major forms of IBD characterized by acute and chronic inflammation in the absence of a known pathogen. These inflammatory disorders are distinguished by the depth and location of inflammation with ulcerative colitis being limited to the mucosa of the colon and Crohn's disease involving both the small intestine and the colon in a transmural fashion. The patho-genesis of Crohn's disease and ulcerative colitis is multifactorial, resulting from the interplay of genetic predisposition, environmental and immunological factors 21 . Initiation and perpetuation of the intestinal inflammation in this chronic disorder has been thought to result from dysregulated immune response to commensal bacteria in the genetically-susceptible host. For instance, the efficacy of fecal diversion and the recurrence when the fecal stream is restored 22, 23 , the existence of subpopulations who can be improved by antibiotics or probiotic treatment 24 , and the...
For some major diseases, such as inflammatory bowel disease, the aetiological agent has not been identified, despite rapidly advancing genetic and molecular research. Conversely, coeliac disease, another serious and common gastrointestinal inflammatory disease, is caused by a well-characterized immune response to wheat-derived proteins.
Nal tract colon, rectum, anus, and peri-anal region. Patients present with a variety of diseases such as colorectal cancer, inflammatory bowel disease, motility disorders, diverticulitis, anal fissures and fistulas, fecal incontinence, and constipation. Colorectal surgeons can perform both endoscopy and major abdominal operations.
Genome-wide linkage screens performed in the UK and the US have revealed suggestive markers of linkage on chromosomes 1, 2, 5, 6, 9, 10, 16 and 19 in one screen 50 and markers of interest on chromosomes 1, 3, 4, 5, 6, 10, 11, 16, 17, and 19 in the other screen 51 . The discrepancies between the two screens is most likely explained by the small contribution ( s
Inflammatory bowel disease (IBD) The general name for diseases that cause inflammation of the bowels, including ulcerative colitis and Crohn's disease. Although these two diseases are similar, there are also some important distinctions. Inflammatory bowel disease (IBD) occurs most often among people aged 15 to 30, but it can affect younger children. There are significantly more reported cases in western Europe and North America than in other parts of the world. Scientists do not yet know what causes inflammatory bowel disease, although they suspect that a number of factors may be involved, including the environment, diet, and heredity. Smoking appears to increase the likelihood of developing Crohn's disease. A new theory suggests that Crohn's disease may be caused by infection (similar to cat scratch disease).
Crohn's disease IBD1 Inflammatory bowel disease that seems to have both genetic and environmental causes not well understood but generally considered likely to be autoimmune. Mutations in the CARD15 gene (caspase recruitment domain-containing protein 15) are associated with susceptibility to Crohn's disease in some families.
A 65-year-old man with a body mass index (BMI) 30 kg m2, who received irradiation treatment for prostate cancer five years earlier, was found to have a 2 cm3 carcinoma of the cecum during routine colonoscopy. The patient had been suffering from inflammatory bowel disease for many years and has a parent with a history of documented venous thrombosis who tested positive for both heterozygous factor V Leiden and prothrombin 20210A. The patient also had these thrombophilic defects but had never suffered a thromboembolic event. The patient required a laparoscopically assisted colon resection lasting 2 h 30 min. The patient did well postoperatively and was discharged six days later. There are no specific data based on prospective randomized trials on VTE risk and prophylaxis in a group of individuals with this combination of risk factors. That is not to say there are no relevant data because it is known that age 60 years, BMI 30 kg m2, family history of VTE, inflammatory bowel disease, a...
Chronic amoebic colitis is clinically indistinguishable from inflammatory bowel disease and those receiving corticosteroids are at risk for toxic megacolon and perforation and may sometimes necessitate parenteral therapy when patients are unable to tolerate the oral route. Infective trophozoites can migrate hematogenously to the right lobe of the liver, causing abscess formation, abdominal pain, jaundice and fever. Adjacent anatomical structures, such as the pulmonary parenchyma, peritoneum and pericardium can become involved. Amoebae can also disseminate to the brain. Immunosuppressed or malnourished individuals, those at the extremes of age, patients with malignancy, and women during pregnancy and post-partum stages are especially at risk for invasive amebiasis. Metronidazole followed by a luminal agent is the therapy of choice in extraintestinal disease. Since amebomas can mimic adenocarcinoma, a biopsy may be needed to differentiate disease. Indications for surgical drainage of an...
Keratinocyte growth factor expression is significantly upregulated in several epithelial injury conditions, including incisional and excisional skin wounds (12,13), surgical bladder injury (14), lung and kidney chemical injury (15,16), inflammatory diseases such as inflammatory bowel disease (IBD) (17-19), and psoriasis (20). Although KGF does not appear to be important for organogenesis because the KGF knockout mice develop normally (21), this pattern of expression strongly suggests that KGF plays an important role in epithelial homeostasis in adult organs, particularly during epithelial regeneration and repair.
The commonest indications include investigation of altered bowel habit, rectal bleeding, suspected colorectal cancer and inflammatory bowel disease. Colonoscopic screening for colon cancer is advocated for patients at high risk, for example, those with a strong family history of the disease, and there is a debate about introducing population-wide screening.
In the classic presentation of CD, the differential diagnosis of malabsorption includes distinguishing between the following diseases tropical sprue, celiac disease, Whipple's disease, irritable bowel syndrome, and inflammatory bowel disease (Crohn's disease and ulcerative colitis). Steatorrhea is often present in malabsorption syndromes and seldom assists in the differential diagnosis.
Another way of achieving selective effects is to only apply the medication where it can reach the target tissue. In the gastrointestinal system, this can be achieved by oral administration of non-absorbed drugs that then act locally. The 5-aminosalicylic acid (5ASA, mesalazine) drugs used to treat inflammatory bowel disease (IBD) are delivered this way, either as slow-release preparations that dissolve in the distal intestine or as pro-drugs that are activated by bacterial metabolism in the colon.
In addition, many gastrointestinal disorders are treated jointly by physicians and surgeons, who collaborate to determine the best combined therapeutic approach for individual patients, particularly when managing inflammatory bowel disease (IBD) and hepatobiliary conditions.
A 32-year-old Caucasian male presented to the emergency department with complaints of bloody diarrhea 20 times per day and dehydration. A CBC was notable for anemia with normal white blood cell and platelet counts. Past medical history was significant for Crohn's disease diagnosed at age 20 involving the small and large intestines. He underwent ileocecal resection, and had been asymptomatic and required no therapy for the past 5 years. During his 2-day hospital course, anemia and dehydration were corrected, the diarrhea resolved, and immunosuppression with prednisone and azathioprine was started to treat a flare of inflammatory bowel disease.
And immunosuppressive agents to treat inflammatory bowel disease, rheumatic and hematologic autoimmune diseases, and following solid organ transplant. Thiopurine drugs are inactive and require metabolism of the prodrug to thioguanine nucleotides (TGN) for cytotoxic and immunosuppressive action. TGNs are formed after a series of enzymes modify the prodrug (Fig. 74.1) beginning with hypoxanthine guanine phos-phoribosyl transferase (HGPRT). While the exact mechanism of the effects of these drugs is unknown, theories include TGN incorporation into and interference with DNA and RNA synthesis and chromosomal replication, inhibition of T and B cell proliferation, and interference with natural-killer (NK) cell cytotoxicity.4'5
A hollow tubular structure into which nutrient-rich food is coerced, and from which wastes are expelled, is found in the most primitive multicellular organisms, from the hydra onwards. In humans, the tract is highly specialized throughout, both structurally and functionally. The mouth and teeth are the first structures in this tract and are connected by a powerful muscular tube, the oesophagus, to the stomach. The stomach stores food after meals and is the site where major digestive processes commence. The small intestine is the main digestive and absorptive surface. The large intestine acts mainly as a reservoir for food waste and allows reabsorption of water from the mainly liquid material leaving the small intestine. It is not essential for life and, paradoxically, is affected by a number of common, serious diseases, such as inflammatory bowel disease and colorectal cancer.
Despite the extremely high concentrations of bacteria and their products in the intestine, intestinal epithelial cells do not activate proinflammatory pathways in the normal state yet are able to control against microbial invasion. One would assume that if intestinal epithelial cells respond to normal commensal bacteria, it might result in excessive immune activation leading to dysregulated mucosal inflammation as is seen in inflammatory bowel disease (IBD). How then does the mucosal immune system regulate a homeostatic balance between tolerance and immunity to the numerous bacteria and dietary constituents of the gut lumen Although the principal role of TLR signaling in the intestine is the same as that in other tissues, i.e., defense against pathogens, it may need to play a unique role in the specific situation of the gut. Due to the close proximity and high density of PAMPs in the intestinal lumen, we postulate that a variety of mechanisms have evolved to protect against...
Dysregulated immune responses are implicated in coeliac disease, where there is hypersensitivity to peptides derived from wheat and other cereals and in inflammatory bowel disease (IBD). Inflammation may normally be actively prevented by subsets of T lymphocytes, which might have regulatory functions that are defective in IBD.
From infants who are failing to thrive to teenagers with possible signs of inflammatory bowel disease, the gastroenterologist plays an integral role in tough cases where a diagnosis is not known. Upper and lower endoscopy are your tools to visualize the disease process within the patient's gastrointestinal system and to biopsy the tissue for help in discerning between immune-mediated, infectious, and neoplastic etiologies. For instance, with infants, you use pH probes to help see whether chronic vomiting is gastroesophageal reflux alone or also due to a milk protein allergy. A significant number of children with chronic medical issues and problems gaining weight need a gastric feeding tube, and you will learn to insert this tube percutaneously aided by endoscopy. Emergencies needing a
A host response to infection, tumors or injury may be to activate the coagulation system within the circulation, resulting in disseminated intravascular coagulation. One of the most severe examples of this occurs in meningococcal septicemia (Dennis et al., 1968), though it occurs less severely but more commonly with solid tumors (Auger and Mackie, 1987). Monocytes and macrophages synthesize and express tissue factor and possibly other coagulation factors (see Section 10.4.6). Mononuclear cells taken from the peripheral blood of patients with tumors of the breast (Auger and Mackie, 1988) and lung (Edwards et al., 1981), inflammatory bowel disease (Edwards et al., 1987) and meningococcal septicemia (Osterud and Flaegstad, 1983) synthesize increased amounts of tissue factor in vitro and a strong positive correlation has been found between the generation of monocyte tissue factor in vitro and in vivo blood coagulation in patients with certain solid tumors (Edwards et al., 1981 Auger and...
Thus, TIR8 represents a negative pathway of regulation of the IL-1R TLR system, with a unique pattern of expression in epithelial cells and DC, crucial for tuning inflammation at mucosal surfaces, in particular in the gastrointestinal tract. Further research is needed to explore the role of TIR8 in controlling inflammation at other mucosal tissues and to investigate its expression and involvement in the pathogene-sis of human diseases, in particular in inflammatory bowel disease.
Abreu, Inflammatory Bowel Disease Center, Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA e-mail maria.abreu mssm.edu Masayuki Fukata, Inflammatory Bowel Disease Center, Division of Gastroenterolo-gy, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA e-mail masayuki.fukata mssm.edu
ANCA Antineutrophil cytoplasmic antibodies ANCA pos-itivity is seen in patients with a variety of inflammatory disorders, including IBD (inflammatory bowel disease), Wegener's granulomatosis and hepatobiliary disorders. Two forms are recognized peripheral ANCA (p-ANCA), where the antigen seems to reside at the periphery of the nucleus and cytoplasmic ANCA (c-ANCA), where the antigen is distributed throughout the cytoplasm of the neutrophil.
Oral health is important because the condition of the mouth is often indicative of the condition of the body as a whole. More than 90 percent of systemic diseases have oral manifestations. These diseases include immune deficiency (e.g., HIV AIDS), viral diseases (e.g., herpes and mumps), cancer and leukemia, diabetes, heart disease, kidney disease, anemia, hemophilia and other bleeding disorders, adrenal gland disorders, and inflammatory bowel disease (Bajuscak, 1999 Glick, 1999). Also, poor oral health can lead to poor general health. Infections in the mouth can enter the bloodstream and affect the functioning of major organs (e.g., bacterial endocarditis, in which infection causes the lining of the heart and the heart valves to become inflamed) (Meadows, 1999). Poor oral care can also contribute to oral cancer, and untreated tooth decay can lead to tooth abscess, tooth loss, and in the worst cases serious destruction of the jawbone (Meadows, 1999).
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