IBD Flashcards
What is IBD
High inflammation of the large intestine. Comes along is a high relapse rate (chance of getting it again and again).
What is the contraction like in the large intestines?
Contraction is more propulsive in small intestine, in large intestine it’s more of squeezing type (think of a bin bag with strings where you pull them and contracts the ends). Bends in the large intestine is where food and unwanted material can become concentrated, contraction is important here to move these along.
Where can IBD be diagnosed in the large intestine?
Crohn’s mainly occurs in the initial part of the ascending colon, then center of transverse and descending colon. This is why crohn’s can be misdiagnosed or completely missed in diagnosis. The ulcerative colitis occurs in the descending colon only.
What are the symptoms of IBD
Inflammation: swelling, redness - increased blood flow – increased temperature, pain. Pain when passing the stool. Redness is only notable inside the colon, but the other symptoms of inflammation are noticeable. Swollen sector can cause increase in pressure and distension, leading to blood in diarrhoea, loss of blood and weight loss follows.
What is the main difference? Site of infection. In CD there are skipped lesions but in UC the ulcers are present in the lower part in continuity.
Diagnosis of CD vs UC
Crohn’s disease extends to all the muscles, and deeper layers of the intestinal wall. This leads to wall pipe thickening and the lumen is narrowed. There will be areas of abnormality and different textures within the length of the muscles (hard and soft).
In UC the ulceration is limited to the lining, but they are open, meaning they are connected to the lumen of the intestine. In an active phase they are red, but in an inactive they appear featureless. Every part of the GIT is inflamed.
What are the macroscopic features of CD vs UC
CD:
Transmural inflammation. Extends into the deeper layers of the intestinal wall. Bowell wall thickened and rigid (hosepipe thickening), lumen narrowed. Affected mucosa: fissuring and serpiginous ulcers. “Cobblestoning” Affected serosa: granular and fibrotic fat “wrapping”
UC:
Ulceration and inflammation of the inner lining of the colon and rectum. Characteristic ulcers or open sores. Active phase: mucosa red, friable, granular, oedematouse. Quiescent phase: mucosa atrophic and featureless
How do genetics and environmental factors affect the prevalence?
Genetics: These affect the normal microbes in the large intestine.
Environmental factors: More meat is eaten in the areas where the is higher prevalence. Whereas areas in with lower prevalence eat more fibrous foods like potatoes and vegetables.
What are the symptoms and long-term complications of IBD? (slide 12)
Main ones: rectal bleeding, bloodied stool (due to stool rubbing against bloodied walls), diarrhoea, weight loss, fever, change in menstrual cycle
What affects pathogenesis of IBD?
The pathogenesis of IBD. Genetic, microbial, and environmental factors participate to disrupt normal microbes on the intestinal barrier. The defective mucosal integrity starts a complex vicious cycle that leads to, enhances, and perpetuates IBD.
Microbiota: Group of microorganisms that resides in a previously established environment. Dysbiosis is an unhealthy change in the normal microbiota.
What leads to IBD in simple terms?
Cells are so closely packed together there are no openings, it prevents the bacteria from entering the blood. Anything that disrupts this barrier leads to IBD. Along with this if microbial dysbiosis occurs it can cause IBD. Also defects in the number and function of Paneth cells, andincreased intestinal permeability can also result in increased bacterial exposure to the blood and muscles.
What is involved in defective mucosal integrity?
Physical barrier
- Mucus layer
- Tight junctions
Specialised epithelial cells:
- Goblet cells: mucus, repair & inflammation modulatory factors
- Paneth cells: anti-microbial peptides (α-Defensins)
Mucosa Innate immune function:
- Pattern recognition receptors (NOD - like receptors) that mediate responses to microbiota
- Divert to tolerance or inflammation pathways
What are the main events of intestinal inflammation?
Breakdown in mucosal barrier function. Lamina propria exposed to antigens
Infiltration with immune cells (Neutrophils, macrophages, dendritic cells, NK cells, B & T cells)
Local elevation of TNFα, IL-1β, IFNγ
T effectors differentiation: Local elevation of Th17 cells. Th1 raised in CD vs Th2 raised in UC. Th17 raised in both.
Defective regulation of immunosuppression (Tregs)
Chronic inflammation: Activated T cells activate other inflammatory cells like macrophages and B cells and recruit more inflammatory cells.
Good bacteria influenced by bad bacteria to turn bad.
T killer cells and macrophages kill cells in the viscinity.
NOD2 mutation affects paneth cells.
How is the muscle affected in CD vs UC?
All the muscles in CD are used and therefore it thickens, reducing the lumen.
In UC only the initial part of the lumen is affected so it forms polyps (projecting growth of tissue from a surface in the body) in those areas.
What are some of the genetic problems with IBD?
Associated with 20% of IBD patients - 3-20 times higher incidence in first degree relatives.
Genetic influence is lower in UC than in CD
- Defects in mucosal barrier: exposure to bacterial products. MUC19, OCTN, DLG5
- Defects in bacterial sampling: Pattern recognition receptors Nod2 (CARD15) (bacterial peptidoglycan receptor), TLR (LPS receptor) – fails to recognise the bacteria is a normal flora
- Defects in immune response: IL23R defect, IL-10 pathway, INFγ gene, Autophagy genes (ATG16L1)
What are some environmental factors of IBD
- Microorganisms
- Diet
- Infections
- Stress
- NSAIDs
- Appendectomy
- Smoking
- Antiobiotics
