Crohn's disease Flashcards
What factors can cause IBD?
Genetic - issues with antimicrobial peptides, autophagy (removing damaged cell parts), cytokines, response to bacteria
Environmental - diet, infections, microenvironment, stress, NSAIDs, smoking, antibiotics use
What maintains the gut wall barrier?
Commensal bacteria
Paneth cells - secrete antimicrobial peptides
Goblet cells - secrete mucous
M cells - in Peyer’s patches, transport pathogens and antigens to macrophages
What is the pathophysiology of Crohn’s?
Translocation of microbial products through M cells, or through the barrier due to impaired function - which activates immune cells
Macrophages phagocytose the bacteria and present the antigens to CD4 T cells
Macrophages and CD4 t cells release cytokines: TNF-A, IL-1, IL-6
Continuously released > chronic inflammation
TNF-A stimulates angiogenesis, induces paneth cell necrosis - antimicrobial cells destroyed, IEC death - impaired barrier function, increases immune response - further damage
What occurs in lactose intolerant patients?
Lactase enzymes not expressed, lactose does not break down, continues through to colon
Gut flora ferment lactose into H2, CO2 and CH3 gases and short chain fatty acids which aren’t absorbed
Unabsorbed lactose and fatty acids increase osmotic pressure -> influx of water -> diarrhoea
What tests can be used to detect lactose intolerance?
Hydrogen breath test: drink lactose drink, hydrogen in breath measured at regular intervals. Breathing out excessive H2 shows lactose isnt being absorbed
Lactose tolerance test: 2hrs after lactose drink, bloods taken to measure glucose levels. If levels havent risen, shows lactose isnt being absorbed > broken down into glucose and galactose
How is lactose normally processed in the body?
Lactase breaks down lactose into glucose and galactose
Lactase enzyme expressed in enterocytes in SI
Glucose and galactose then absorbed into epithelium, and into bloodstream via SGLT2 and GLUT2 co-transporters
How may IBD affect absorption?
Inflammation and damage to intestinal lining can disrupt SGLT1 and GLUT2 and other transporter function -> impaired glucose absorption
How are lipids absorbed into the gut?
Monoglycerides and fatty acids combine with bile salts -> micelles
Water soluble and diffuse to brush border and absorbed by endocytosis
Lipids combine with fatty acids, reassembled into triglycerides on SER
Packaged into chylomicrons in golgi apparatus, enter lymphatic system, then bloodstream
How are amino acids absorbed into the gut?
Via specific amino acid transporters across apical membrane
Di and tri peptides absorbed via H+ dependent cotransporters
Form complete proteins before moving into bloodstream by facilitated diffusion
How is fructose absorbed in the gut?
Fructose is transported across apical membrane into cell via GLUT5 receptor
Transported into interstitial space across basolateral membrane via GLUT2 receptor
How are glucose and galactose absorbed in the gut?
Glucose and galactose transported with sodium across apical membrane through the sodium/glucose cotransporter (SGLT1) - two Na2+ for one monosaccharide
Glucose and galactose enter interstitial space via GLUT2 receptor across basolateral membrane
What are the diagnostic tests for Crohn’s disease?
Colonoscopy
Biopsy
Blood tests: FBC, serology test, ferritin/transferrin, U&E
Hydrogen breath test
Barium swallow
Stool test
What is shown in the barium swallow for diagnosis of Crohn’s?
Cobblestone appearance on the x-ray due to fissures and ulceration in the intestine
String sign of Kantor - stricturing of the intestine and ‘creeping fat’ pushing intestine away
What is tested in a stool test to diagnose Crohn’s disease?
Calprotectin is a calcium and zinc-binding protein found in neutrophils
Prescence of calprotectin in faeces is a result of neutrophil migration into the GI tissue due to the inflammatory process
Faecal calprotectin levels correlate with inflammation, so used as a biomarker
What is analysed in a blood test to test for Crohn’s? 5
Can’t directly diagnose IBD, but looks for inflammation in the body looks at:
Serum FBC: Higher WBC count / higher platelet count
Serology test (serum inflammatory markers): antibodies, autoantibodies and microbial antigens, high CRP and ESR.
Ferritin and transferrin (anaemia), vitB12, folate, vit D levels - nutritional deficiencies
U&Es - signs of dehydration: high sodium, low potassium
Serum LFTs: low albumin
How can a hydrogen breath test be used to identify Crohn’s?
Hydrogen breath test can identify or rule out lactose intolerance
What is the prevalence and incidence of Crohn’s disease?
Prevalence: 145 in 100,000
Two age peaks - 20-30 yrs and 50 yrs
Incidence: 3-20 per 100,000
What are the risk factors for Crohn’s disease?
Family history: 20% have affected family member
Age: majority diagnosed before 30
Smoking: increases risk by x3, mor aggressive disease
Medications: NSAIDs - cause bowel inflammation
Other medications: upper resp tract infections, enteric infections
What is the difference between IBS and IBD?
IBD= structural (can be observed in scans, examinations) can be positively diagnosed
IBS= functional (affects function, cannot be observed visually) diagnosed by exclusion
What are the differences between UC and Crohn’s?
UC is limited to large intestine, Crohn’s can be anywhere in the GI tract
UC inflammation only involves mucosa, Crohn’s inflammation extends through all layers of the gut wall
UC has continuous inflammation, Crohn’s has discontinuous inflammation
Crohn’s shows longitudinal ulcers, cobblestone mucosa
What would be the endoscopy findings for ulcerative colitis?
Edematous mucosa - fluid accumulation
Erythema - redness
Loss of vascular markings
Mucosal friability (easily damaged by touch)
What are the non-GI symptoms of ulcerative colitis?
Mouth ulcers
Shortness of breath
Irregular heart rate
Finger clubbing
Uveitis
Arthritis
What are the symptoms of ulcerative colitis?
Bloody diarrhoea > 6 weeks
Rectal bleeding
Faecal urgency
Nocturnal defecation
Tenesmus - feel need to defecate, but can’t
Abdominal pain
Weight loss
Fatigue
What is ulcerative colitis?
Chronic, relapsing, remitting, non-infectious inflammatory GI tract disease
Inflammation limited to mucosa
Usually effects rectum and extends proximally continuously
