GI enzyme, UC + Crohns Flashcards
What do the intestines absorb?
Nutrients
Water
Electrolytes
What conditions are required for absorption?
Very large surface area
Slow movement
Mostly active so ATP required
Describe the structure of the small intestine?
Mucosa folded into villi, separated by crypts
Cells multiply in the crypts and migrate towards tips of villi, maturing as they go - acquire capacity to absorb, micro-villi on luminal surface increases surface area enormously (brush border)
They are then shed from the villus tips
Mucosa therefore constantly renewed ‘unstirred layer’
What do the villi do?
Increase surface area
Cells on them are very active
Secrete enzymes into brush border:
- Forms unstirred layer
- Almost digested nutrients diffuse into unstirred layer where trapped enzymes complete digestion
- Steadily releasing small molecules for absorption
What are the 2 forms of starch?
Amylose - straight chains with alpha 1,4 bonds
Amylopectin - branched with alpha 1,6 bonds at branches
What does alpha amylase do?
Acts at alpha 1,4 bonds
Yield maltose from amyloses
Yields alpha limit dextrins from amylopectins
Where are alpha amylases secreted?
In saliva and by pancreas
How is glucose created?
Isomatase breaks down branched molecules at a-1,6 bonds
Maltase breaks down maltose to glucose
Sucrase
Lactase
How is glucose absorbed in the intestine?
Absorbed actively using energy from sodium gradient
Glucose enters mucosal cells via Na/glucose transporter - SGLT1 (also transports galactose)
Leaves cell to ECF y facilitated diffusion - GLUT2 transporter
How are fructose and lactose absorbed?
Facilitated diffusion not linked to Na+
What stimulates maximum water uptake?
Na+ generates osmotic gradient and drive uptake of glucose which also generates a gradient of its own - Oral rehydration fluid
What enzymes digest proteins to amino acids?
Protein -> oligopeptides in stomach by pepsin from chief cells (likes bonds near aromatic side chains
Trypsin in the duodenum breaks bonds near basic side chains
Chromotrypsin breaks bonds near aromatic side chains
Carboxypeptidase breaks C terminal amino acids with basic side chains
How are proteins absorbed into the body?
Both amino acids and small peptides absorbed but not proteins in adults. Brush border enzymes break down oligopeptides further. Amino acids taken up by active and passive processes
What types of Na+/amino acid co-transporters are there?
Small neutral amino acids Neutral amino acids, basic amino acids and cystine Acidic amino acids Imino-aminio acids Beta amino acids
Describe the process of absorption of amino acids.
Some uptake of amino acids by facilitated passive diffusion
Dipeptides and tripeptides taken up by active mechanism associated with active pumping of H+ into lumen
Return H+ by co-transport with peptide
How are electrolytes and water absorbed in the intestines?
Sodium taken up via diffusion into cell and active transport across basolateral membrane.
Chloride follows
Osmotic gradient from all absorption leads to uptake of water
Describe the uptake of calcium.
About 700mg absorbed of 6g consumed
Enters cell by facilitated diffusion (low intracellular concentration)
Pumped out of basolateral membrane by Ca2+ ATPase
Both process require vitamin D and are stimulated by parathyroid hormone
Describe the uptake of iron.
About 20mg/day absorbed mostly in haem or related pigments
Gastric acid important for Fe absorption - solubise iron complexes
Stomach also secretes gastroferrin - solubises iron
Mucosal cells secrete transferrin which binds Fe2+ in the lumen.
Complex taken into cells by endocytosis
Fe2+ liberated and exported to blood where it binds again to transferrin
How are vitamins absorbed in the intestines?
Water soluble vitamins absorbed largely by passive diffusion (C and Bs)
Vit B12 absorbed with co-factor in terminal ileum only (intrinsic factor secreted by stomach mucosa
What happens when a person is B12 deficient?
Pernicious anaemia. Stomach damage, terminal ileum removed
Describe intestinal motility.
Very slow (hours)
Gentle agitation required
Not peristalsis - segmenting
Where are the intestinal pacemakers located?
At intervals along the length of small intestine. Each pacemaker drives a short section of intestine causing intermittent contraction of smooth muscle along the length. ‘Segments’
What is the intestinal gradient?
Frequency of pacemaker highest at stomach end - form about 12 -> 8 per minute
What does segmenting do?
Mixes and agitates content
Intestinal gradient causes gradual caudal progression
More rapidly segmenting cephalic segment squirts more frequently into adjacent caudal segment than that segment does into it
What is “Haustral shuttling”?
Colon divided naturally into segments known as haustra
Longitudinal muscle reduced to taenia coli
Contraction of smooth muscle in walls of haustra shuffles contents back and forth
Slow absorption of most remaining water and salts - forming faeces
With gentle pregression towards sigmoid colon
Control like segmenting
What is the purpose of peristalsis in the small intestine and when does this occur?
When it is mostly empty a peristaltic movement may occur to move any debris left in it
What is meant by “Mass movement” in the large intestine?
Peristaltic, propulsive pattern from transverse through descending colon
Forces faeces rapidly into rectum which is normally empty
Induces urge to defecate
Often triggered by eating - Gasto-colic reflex
Infrequent - once or twice a day
What induces the urge to defaecate?
Filling of rectum by mass movement:
Pressure receptors
Waves of contraction in rectal muscle
Forces faeces towards anus
Describe the anal sphincters.
Internal - smooth muscle under parasympathetic control (relaxes)
External - striated muscle under voluntary control (relaxes)
What causes relaxation of anal sphincters?
Increase of intra-abdominal pressure
Control via sacral reflexes modified by higher centres
Higher centres overridden if rectal pressure too high
What is crohn’s dieae?
A condition of chronic inflammation potentially involving any location of the GIT from mouth to anus
What is ulcerative colitis?
An inflammatory disorder that affects the rectum and extends proximally in continuity to effect a variable extent of the colon
What are the causes of intestinal inflammation and infection?
Ulcerative colitis Crohn's disease Diversion colitis Diverticular colitis Radiation, drug, infectious, ischaemic colitis
What are the clinical presentations associated with ulcerative colitis?
rectal bleeding
diarrhoea
abdominal pain
What is the mechanism of ulcerative colitis?
The mucosa of UC patients is dominated by Th2 (T-helper) cells, which produce Transforming growth factor (TGF) and IL-5
How does crohn’s disease present?
Upper GI involvement: - Nausea and vomiting - Dyspepsia - Small bowel obstruction - Anorexia and weight loss - Loose stools Colonic disease: - diarrhoea - passage of obvious blood May be anaemia if terminal ileum involved due to poor absorption of B12
What is the mechanism of crohns disease?
The mucosa is dominated by Th1 (T-helper) cells, which produce Interferon Gamma (IFN-gamma) and IL-2
What risk factors might be involved in the development of IBD?
Genetic predisposition
NSAIDs - alter intestinal barrier (?)
Early appendectomy - increased incidence of UC
Smoking - protects against UC but increases risk of CD
What are the triggers of IBD?
Antibiotics (gets rid of normal flora) Diet Acute infections NSAIDs Smoking (crohns) Stress
What is the depth of inflammation of UC and CD?
UC - Mucosal
Crohns - Transmural
Are fistulas and perianal disease more common in UC or CD?
Crohn’s disease
What cancer are patients with UC or CD more susceptible to?
Colorectal (small bowel also with crohn’s, depending on location)
Whatare the common methods used for investigation of IBD?
Colonoscopy - biopsy of involved mucosa and viewing of ulceration
Stool analysis - parasites, C. diff. toxin, culture
Barium radiographs
CT scan
Capsule endoscopy
Plain x-ray if bowel obstruction or perforation suspected
What are the macroscopic changes in Crohn’s disease?
Bowel involved thickened and often narrower
Deep ulcers and fissures in mucosa may produce cobblestone appearance
Fistulae and abscesses may be present, which reflect penetrating disease
What are the macroscopic changes of ulcerative colitis?
Mucosa looks reddened, inflamed and bleeds easily
Extensive ulceration in severe disease with the adjacent mucosa appearing as inflammatory (pseudo) polyps
Collar button ulcers - ulcer through the bowel mucosa to the muscle then up and down in a T shape
What are the microscopic changes of Crohn’s disease?
inflammation through all layer of the bowel (transmural)
Increase in chronic inflammatory cells
Lymphoid hyperplasia
Granulomas (TH1 response)
What are the microscopic changes in ulcerative colitis?
Superficial inflammation
Chronic inflammatory cell infiltration in the lamina propria
Crypt abscesses
Goblet cell depletion
How are some of the diagnostic difficulties in separating CD/UC?
Usually can be made on basis of clinical, radiological and histological differences seen in biopsy
If biopsies are obtained in the acute phase, considered to have colitis of undermined type and aetiology (CUTE)
Serological testing for anti-neutrophil cytoplasmic antibodies in UC and anti-saccharomyces cervisiae antibodies in CD may be of value in differentiating the two conditions
What are the common treatment options for Crohn’s disease?
Induction of remission: Oral or IV glucocorticoids, enteral nutrition, anti-TNF antibodies (infliximab)
Maintenance of remission: Methotrexate, azathioprine, anti TNF antibodies
Perianal disease: Ciproflaxacin and metronidazole, azathioprine, anti-TNF antibodies
Anti-TNF antibodies bind to membrane bound TNF-alpha and induce immune cell apoptosis
Surgical management if failure of therapy or if complications. Colectomy and ileorectal anastomosis may be performed
What is the treatment of ulcerative colitis?
Distal diseaes: topical or suppository corticosteroids
Left sided: topical corticosteroid enema
Extensive colitis: oral corticosteroids
Surgical management: patients with complications / corticosteroids dependence. In acute disease, subtotal colectomy with end ileostomy and preservation of the rectum is the operation choice.
