Digestion 4 Flashcards
Immune Disorders of GIT descriptive words
Aetiology (cause)
Immunopathogenesis (allows disease to progress)
Pathological & pathophysiological
effects (ability to get nutrition)
Complications, prognosis & prevention
Name diseases
what are the three factor that predispose you to disease?
Inflammation- (IBD) inflammatory bowel disease
crohn’s disease and Ulcerative colitis
hypersensitivity (allergic) disease
Coeliac disease
genetics
environment
immunological factors
“For every action, there is an equal and opposite reaction.” Isaac Newton
In normal gut homeostasis we have a balance so we can have a controlled response against pathogens
Inflammatory Bowel Disease
affected areas
Idiopathic (unknown what triggers response), chronic, Inflammatory both crohn’s and ulcitilaritus.
Crohn’s disease it can happen anywhere along tract from mouth to anus. small and large intestines
Ulcerative colitis is restricted in the large intestine (colon)
crohn’s disease with the involvement of the small intestine might affect the digestion and absorption of Bile salts
Fat, fat-sol, Vits, Protein dig, CHOs dig.
Ulcerative colitis can affect absorption of minerals electrolytes, trace elements and water
IBD Pathologies images
crohn’s, histology is obliterated and has thickened wall due to infiltration of immune cells very purple in screening as staining due to inflammation. (cobblestoning). restricts luminal space for digest, destructive that can lead to fissures, it is transmural across all layers of the tracts.
ulcerative colitis produces distortion of crypts, has pseudopolyps which have liquid filled blisters and is restricted to mucosa.
Crohn’s disease (CD)
describe symptoms
A condition in which segments of the intestine become inflamed, thickened and ulcerated. Affects whole length of tract but affects predominantly the terminal ileum
*Symptoms;
skip lesions (active area of inflammation, and areas of tract that look normal because it skips)
partial obstruction of lumen in tract
pain
diarrhea (malabsorption)
fissures form fistulae (holes and tunnels)
pinching tract so lumen is smaller
*Treatment;
food rest
corticosteroids (immunosuppressant)
immunosuppressive drugs
antibiotics
Surgery (resection, shortened tract by removing unhealthy areas)
can affect all 4 layers
CD: genetic pre-disposing elements
genetic variations and mutations and these are antigen-presenting molecules.
HLA-DR1 & DQw5 (present antigen)
NOD2 IBD1 (R702W, G908R, 1007fs, R713C, E843K)
TLR4 (A299G)
TLR9 (-1237 T – C, 2848 G – A) (pattern recognition factors innate response)
PPARy
OCTN IBD5 (organic cation transporters (scaffolding)
DLG5 (113G-A nt polymorphism resulting in R30Q)
Scaffolding protein involved in maintenance of epithelial integrity
NFKBA1?
Pathogenesis of CD
Crohn’s is driven by cell-mediated immunity (intracellular pathogens)
CMI (Mycobacterium avium paratuberculosis suspected)
[eicosanoids, Cytok., proteases, ROI, clotting/fibrous, permeability]
Increased M() & T cell infiltration & activation
M() activation:
lysosomal NZMs
plasmin – tissue damage
Granulomatous delayed Type IV Hypersensitivity (DTH)
cell mediated immunity predominates in Crohn’s disease
*There is some Humoural immunity as well
Polyclonal B cell activation
Immune complexes (ICs) 2o pathology to lesions
Increased C3 component expression
Prolonged DTH response: granuloma formation
CD granuloma:
- Composed of epithelial histiocytes
- Granuloma often found in LNs
- Necrosis absent in granuloma
cell mediated immune t-cells with effect of cells downstream, specialised macrophages so cell mediated immunity, more granulomas, less likely the tract can have its normal processes.
Describe process of Crohn’s disease
Harmful organisms may get through barrier by genetic influences they get processed and activate certain T-cells involved in cell mediated immunity which help activate macrophages. This then drives inflammation and what they produce activates T-cells again and other inflammatory mediators. This destroys the epithelial wall and means that good bacteria may get in as well but it could still trigger this inflammatory response
Ulcerative colitis (UC)
Idiopathic proctocolitis
Inflammation and ulceration of the colon/rectum.
A relapsing/remitting disease.
active inflammation and rest periods (cycle)
UC lesions in Mucosa (top layer) no sub-mucosal involvement.
idiopathic
Symptoms;
inflammation of mucosa
diarrhea
blood in stalls
mucus
lower abdominal pain
Treatment;
corticosteroids
sulphasalazine
food rest
surgery (take out inflamed area)
more localised just first layer
UC: genetic pre-disposition
positive HLA-DR2 (MAC molecules)
Negative association with HLA-DR7
TLR4 (Thr399Ile)=mutation receptors of innate immune systems that recognises bacteria in particular LPS of gram negative bacteria so inflammatory destruction or reorganization of tissue
Pathogenesis of UC
Humoural (predominant)
predominated by antibody production by B-cells
AutoAntibodies against colonic epithelial cells destruction of epithelial cells
Igs: cross-reactive E.coli Ags vs. Epithelial cells
Circulating Immune complexes (ICs) (IgG & IgA)
(IgG1 > IgG2) drives inflammatory response
Complement activation by local ICs (& LPS)
CMI (Less effective in UC than CD)
Increased infiltration of Mfs, Lfs, BPlasma & PMNs
[eicosanoids, Cytok., proteases, ROI, clotting/fibrous, permeability]
M()s: less mature, more mobile (chemotaxis)
increased lysosomal NZM activity (neutral proteinases)
T cells: Hypersensitivity to colonic epithelium (No granulomata)
CMI to enterobacterial Ag (Kunin)
ADCC by NK cells
Describe process in UC
A different activated T-cell that drives antibody production and activates different cells and factors of inflammation. With destruction of mucosa they may be perpetuated by the safe bacteria
Coeliac Disease (hypersensitivity, allergic disease)
“Coeliac disease is a permanent intolerance to gluten,resulting in damage to the intestine & is reversible with avoidance of dietary gluten.”
Symptoms:
stunted growth / bone problems
decreased nutrient absorption
distended abdomen
diarrhea
bulky, pale, frothy foul-smelling stools inability to process fat (fatty – steatorrhea)
anaemia (tiredness, shortness of breath, fluid retention)
Treatment: Gluten-free diet.
