GI Session 8 Flashcards
How is the large SA needed for absorption in the intestines achieved?
Mucosa permanent folded in pliae circulares
Enterocytes have microvilli –> brush border
Say does the intestinal epithelia consist of?
Enterocytes
Goblet cells
Intestinal glands/crypts between villi
What cells are present in the intestinal crypts?
Intestinal stem cells Paneth cells Transit amplifying cells Goblet cells Enteroendocrine cells Enterocytes
What is the function of Paneth cells?
Part of innate immune system which possess antivirals and antimicrobials in eosinophilic granules
What happens to cells in the intestinal crypts?
Start from bottom of crypt and migrate and matured urging transit becoming more differentiated as they reach the surface
What happens to cells when they reach the top of the intestinal crypts?
Undergo anoikis - programmed cell death due to loss of contact with cells
Why does the intestinal mucosa have a high turnover of cells?
Sloughed off into faeces and replaced every 3-6 days
What is the function of cells on the villi in the intestines?
V. actively secrete enzymes into the brush border to break down carbohydrates and proteins in order to complete digestion
Describe the stages of carbohydrate digestion.
Starch broken down by alpha-amylase (saliva) and amylase (pancreas) –> glucose, maltose and alpha dextrins –> brush border enzymes –> monosaccharides–> enterocyte absorption
What form do carbohydrates have to be in to be absorbed by the gut?
Monosaccharides
Why is alpha-amylase short acting?
Due to stomach acid
What binds do amylase act in in carbohydrate digestion?
Alpha 1-4
Why does amylase action on amylopectin result in?
Alpha dextrins
What brush border enzymes are found in the intestines?
Isomaltase: alpha 1-6 Maltase Alpha dextrinase Sucrase: sucrose--> glucose and fructose Lactase: lactose--> glucose and galactose
What is the role of the intestines?
Absorb nutrient, water and electrolytes from conditioned chyme
Barrier to pathogen entry for innate immune defence
How are monosaccharides absorbed?
Na+/K+-ATPase on basolateral membrane maintains low intracellular sodium –> SGLT1 binds sodium which allows glucose binding and both move into cell –> GLUT-2 transports glucose down gradient into capillary –> GLUT-5 allows facilitated diffusion of fructose
Why does a mixture of glucose and salt stimulate maximum water uptake?
Monosaccharide absorption involves sodium uptake so water will follow
What form must proteins be in to be absorbed?
A.a.
Dipeptide
Tripeptide
How is protein digestion carried out by the stomach?
Chief cell releases pepsinogen –> HCl converts it to pepsin –> pepsin on proteins –> dipeptides and a.a. absorbed by small intestine
How does the pancreas function in protein digestion?
Trypsinogen converted by enteropeptidase –> trypsin –> activates other proteases from zymogens –> chymotrypisn and elastase hydrolyse interior peptide bonds, exopeptidases caboxypeptidase A+B hydrolyse from C terminal end
What breaks down oligopeptides further so they can be absorbed?
Brush border enzymes
How are a.a. transported into cells during absorption?
Via neutral/acidic/basic/imino Na+-acid cotransporters using active and passive mechanisms
How are dipeptides and tripeptides absorbed?
Moved into cells by H+ cotransporter and converted by cytolsolic peptidases –> a.a.
What happens in the process of isosmotic fluid uptake in the intestines?
Sodium AT out across basolateral membrane –> sodium diffuses into epithelial cells and paracellular electrolyte movement–> osmotic gradient due to all absorption –> water move in
How do the sodium transporters found in the small and large intestine differ?
Small: Na+ cotransporters on apical membrane which absorbed more sodium
Large: sodium channels induced by aldosterone
How is calcium absorbed by active transcellular mechanisms in the gut?
Ca2+ATPase removes calcium across BLM –> gradient allows facilitated diffusion of calcium by binding to calbindin
What is needed for calbindin to function?
Vitamin D
In which parts of the gut do active transcellular and passive paracellular absorption of calcium occur?
Active in proximal
Passive in distal
How is iron mainly absorbed in the GI tract?
In haem/Fe2+ absorbed across apical membrane –> binds to apoferritin –> across BLM –> binds to transferrin in circulation
What determines levels of iron absorption from the GI tract?
Levels of transferrin in blood
How are vitamins absorbed in the GI tract?
Water soluble by sodium cotransport e.g. Vit C and B
B12 in terminal ileum bound to intrinsic factor
What are the three mechanisms of small intestine motility?
Intestinal gradient
Segmentation
Peristalsis
What is intestinal gradient in small intestine motility?
Between meals intestinal pacemakers have a higher frequency proximally which drives slow caudal progression of contents
What is segmentation in small intestine motility?
Following a meal contraction proximally then distally move contents back and forth so contents is mixed and absorption time is increased
What is segmentation in large intestine motility?
In proximal colon contraction of haustra causes agitation and mixing of contents so most of the remaining water can be removed from faeces
What is mass movement?
Coordinated contraction 1-3x daily which moves contents rapidly from transverse colon to rectum, often triggered by eating
What is the gastro-colic reflex?
Trigger of mass movement caused by eating
What happens in the process of defecation?
Rectum normally empty –> fills to 25% –> urge to defecate –> PNS relaxes internal sphincter, somatic NS relaxes external sphincter, intra-abdominal pressure increases –> expulsion of faeces
What is IBD?
Group of conditions characterised by idiopathic inflammation of the GI tract
What diseases are included in the term IBD?
Crohn's Ulcerative colitis Diversion colitis Pouchitis Microscopic colitis
What is microscopic colitis?
No visible disease process but inflammatory cells are present in the mucosa
What extra-bowel symptoms are commonly experienced in IBD?
Arthropathy
Erythema nodosum/pyoderma gangrenosum/psoriasis
Primary sclerosing cholangitis
Scleritis or episcleritis
What extra-bowel symptom is commonly linked with ulcerative colitis?
Primary sclerosing cholangitis due to fibrosis of bile duct
What can trigger IBD?
Abx
Infections
Smoking
Diet
How do the impacts of smoking differ in Crohn’s and UC?
Increases risk of Crohn’s
Impromptus UC symptoms
What is the gross pathology of Crohn’s disease?
Hyperaemia --> erythema Mucosal oedema Discrete superficial ulcers Deeper ulcers Transmural inflammation --> thickening of bowel wall Cobblestone mucosa Fistulas
What is the gross pathology of UC?
Chronic inflammatory infiltrate of LP Crypt abscesses due to inflammatory cells in crypt and surrounding oedema Decreased goblet cells Pseudopolyps Loss of haustra
What are pseudopolyps?
Oedematous healthy mucosa
What causes cobblestone mucosa in Crohn’s disease?
Ulcers/oedematous tissue pushing through
What is the microscopic pathology of Crohn’s?
Epithelioid granulomas are pathognomonic but not present in all cases
What is seen on investigation of Crohn’s?
Bloods: macrocytic anaemia due to B12 deficiency
CT/MRI: bowel wall thickening, obstruction, extramural problems
Barium enema: strictures, fistulae, string sign
Colonoscopy: cobblestone mucosa, ulcer formation
What is the limit of colonoscopy?
Terminal ileum
What is seen on investigation of UC?
Bloods: iron deficiency aneamia, ANCA
Stool cultures: no infection
AXR/CT/MRI: not useful as only mucosal involvement
Colonoscopy: ulceration connected between patches
What does detection of ANCA in UC suggest?
Autoimmune disease
What is indeterminate colitis?
IBD pts with features of Crohn’s and UC but no defining features on investigation
What are the distinguishing characteristics of Crohn’s disease?
No rectal involvement but anywhere in GI tract Gross bleeding in 25% Perianal disease in 75% Fistulae Malnutrition Transmural inflammation Granulomas >75% Fibrosis common but crypt abscesses rare Skip lesions Aphthous and linear ulcers Contact bleeding rare Cobblestone appearance
What are the distinguishing characteristics of UC?
Rectum almost always involved +/- colon Gross bleeding common Perianal disease rare No fistula or malnutrition Transmural inflammation rare No granulomas or fibrosis but crypt abscesses seen Continuous mucosal involvement Linear and apthous ulcers rare Friable mucosa No cobblestone appearance
What are the main classes of Tx option for IBD?
Lifestyle changes
Medical Tx
Surgical Tx
What medical Tx can be used in IBD?
- Aminosalicylates for flares and remission
- Corticosteroids for flares only due to steroid S/E
- Immunomodulators for active disease or remissive pts who don’t tolerate aminosalicylates
Why are Abx with anti-inflammatory effects not used to Tx IBD?
Lack of infective cause
When is surgery used in Crohn’s?
Repair of strictures of fistulae
Remove small section of bowel in v. active disease
Why is surgery avoided in Crohn’s?
Reduce risk of short bowel disorder
Reduce risk of painful adhesions for repeated surgery
When is surgery used in UC?
Curative via colectomy for unsettling inflammation, precancerous change and toxic megacolon
What is toxic megacolon?
Acute and rapid distension to point of perforation, a systemic condition
