Crohn's Disease
Mild Crohn's
- At this stage, bowel movements occur at a lesser rate. - Little next to no abdominal pain. - Complications outside of intestinal tract are scarce or absent. - No mass detected when abdomen is pressed. - Red blood cell count is normal. - No fistulas, or abscesses.
Diagnostic Procedures
- Colonoscopy - Upper Endoscopy - Sigmoidoscopy - Capsule Endoscopy X-rays - Barium X-ray and CT scans - Blood Cell counts - CRP assay
Severe Crohn's
- In NEED of anti-diarrheal medication, bowel movements are frequent. - Lower right severe abdominal pain. - Low red blood cell count, weight loss, fistulas and abscesses are present.
Surgery
- Resection: Cutting out a significantly damaged portion of the digestive tracts and reconnecting the healthy ends. - Strictureplasty: Widens a narrowed portion of the digestive tract. - Colectomy: Removal of most or all of the colon.
Crohn's in MN
10.7 per 100,000 people
Genes associated with Crohn's
160+
Crohn's in North America
201 per 100,000 in adults, 43 per 100,000 in children
Th1 lymphocytes
Accelerate the inflammatory process by increasing TNF-α release from APCs and by releasing TNF-α themselves, which causes upregulation of adhesion molecules in endothelial cells, which recruits more leukocytes to enter the infected area, causing tissue damage.
Three main gene mutations on Leucine Rich Repeat sequence on NOD2/CARD15 gene:
Amino acid substitution of Arg702Trp Amino Acid substitution of Gly908Arg Frameshift 1007fs region
Treatment for mild Crohn's
Aminosialicylate acid derivative (modulates PPARy and NF-kB regulation)
Organ level pathology
Causes pain, reduced nutrient absorption, intestinal blockage and other complications such as ulcerations (cobblestoning), stenosis, blockages, and fistulas.
What type of disease is Crohn's?
Chronic, autoimmune, Inflammatory Bowel Disease (IBD)
Types of Crohn's
Crohn's (granulomatous) colitis: Affects the colon only. Gastroduodenal Crohn's disease: Affects the stomach and duodenum (the first part of the small intestine). Ileitis: Affects the ileum. Ileocolitis: The most common form of Crohn's affecting the colon and ileum (the last section of small intestine). Jejunoileitis: Produces patchy areas of inflammation in the jejunum (upper half of the small intestine).
Differences between Crohn's and UC
Crohn's can affect the entire GI tract, inflamed tissue can be patchy, and can affect all layers of tissue. UC is limited to the colon, inflammation is continuous, and can affect only the innermost layer of bowel wall. Globally, UC is more common than Crohn's
Regulatory lymphocytes
Dysregulation of these cells results in chronic inflammation. This is one of the primary mechanisms proposed for Crohn's disease manifestations. Basically, the immune system is NOT controlled, and thus chronic inflammation ensues.
Signs/symptoms
Diarrhea, Fever and fatigue, Abdominal pain and cramping, Blood in your stool, Mouth sores, Reduced appetite and weight loss, Perianal disease, osteoporosis, hepatitis, cirrhosis (rare cases), mucogingivitis, eye damage.
Mast Cells
Facilitate some of the inflammation process by increasing capillary permeability (histamine release), This causes endothelial cells to "open", and this causes increased blood flow (edema, redness, heat, pain) and for more leukocytes to enter the tissue.
Non-necrotizing granulomas
Found in CD patients but not in UC patients
Most common GI target areas
Ileum (last portion of small intestine) & Cecum (first portion of the colon)
General Etiopathogenesis
Immunodeficient or dysfunctional innate immunity response in the gastrointestinal tract: begins with the gut flora; commensal enteric bacteria triggers over-stimulation of CD4+ T helper cells expressing pro-inflammatory cytokines.
APCs (Macrophages/Dendritic cells)
Initiate the immune response by processing antigens, and presenting them to TH1 cells, as well as releasing cytokines which increase inflammation and swelling.
Treatment for severe Crohn's
Intravenous corticosteroids + later acid biologic agent and/or surgery if the steroids fail
Prevalence
Less than 200,000 new cases a year; rare
Main leukocytes involved in CD
Mast Cells, APCs (Macrophages & Dendritic cells), Th1 cells, other CD4+ cells
Functioning NOD protein
NOD2 proteins maintain intestinal homeostasis and regulate inflammation; binds to muramyl dipeptide (MPD) and activates NF-kB. This process is critical in clearance of bacterial infection and stimulates production of antimicrobial peptides/defensins and mucin, which restrain and maintain distance between microorganisms and gut epithelial cells.
Genetic predispositions
NOD2/CARD15 gene mutations have been associated with increased risk of CD. Located on chromosome 16; codes for NOD protein.
Complex genetic disorder
Non-Mendalian pattern of inheritance indicates it is not genes alone which cause Crohn's Disease
Treatment for moderate Crohn's
Oral corticosteroids + aminosialicylate acid derivative Immunosuppresive therapy (Decreases pro-inflammatory cytokines IL-1, IL-8 and TNF-α)
Mycobacterium avium subspecies paratuberculosis (MAP)
Potential contributing factor to CD in humans due to inefficient removal of the bacterial. Contains muramyl dipeptide (MDP); MAP survives intracellularly in macrophages; Apoptosis resistant.
NOD protein dysfunction
Protein does not recognize pathogenic components. Compensatory immune response through other pathways drive chronic inflammation.
Environmental/microbial factors
Smoking, nonsteroidal anti-inflammatory drugs (NSAIDS), and certain diet choices have all been linked with CD
Most common demographic
White/Caucasian individuals; with Jewish descendants having 4-5 times greater chance. Most commonly diagnosed between age 15 and 35.
Crohn's Inflammation
Without proper regulation, TH1 cells and antigen presenting cells over-express pro-inflammatory cytokines such as interleukin-1 and tumor necrosis factor-alpha (IL-1 and TNF-α) that up-regulate the production of the adhesion molecules, intercellular adhesion molecule and vascular cell adhesion molecule (ICAM-1 and VCAM-1).
