Physiology and Pharmacology of the Large Intestine Flashcards
How long does it take for material to pass through the large intestine?
Around 18-24 hours
What is entry into the large intestine usually permitted by?
The gastroileal reflux through the ileocaecal sphincter which acts as a one way valve
What is the gastroileal reflux stimulated by?
Gastric distention
What controls the opening etc of the ileoceacal valve?
The vagus nerve - sympathetic and enteric neurones
What does the ‘one way valve’ (ileocaecal sphincter) do?
Prevents colonic bacteria from proliferating into the ileum
Produces an urger to defeacate
Allows the digested contents of the small intestine to enter the caecum
What are the major functions of the large intestine?
Absorption - of H2O, Na+ and Cl-
Secretion - of K+, HCO3 and mucus
Absorption - of short chain fatty acids - carb that is not absorbed by the small intestine is fermented by colonic flora to short chain fatty acids
Reservoir - storage of colonic contents
Periodic elimination fo faeces - under voluntary control
What does HCO3- do?
HCO3- neutralises acid produced by bacterial fermentation
Describe the mass movements of the large intestine?
Strong peristaltic contractions of the circular muscles in large parts of the colon
Happens around 1-3 times each day
Usually triggered by meals (gastrocolic response)
Drives faeces into distal regions
Describe haustration of the large intestine?
Non propulsive segmentation caused by contraction of the circular muscles
Hausfrau are pouches formed in the colon wall
Allows time for fluid and electrolytes reabsorption
Describe the defecation reflex of the large intestine?
A spinal reflex triggered by distention of the rectum
Describe the ‘steps’ in the defecation reflex?
Mass movement - the rectum fills with feacal matter
Activation of rectal stretch receptors
- Activation of afferents to spinal cord (via pelvic nerve)
- activation of parasympathetic efferents
- Contration of smooth muscle of the colon and rectum - internal anal sphincter
- Relaxation of skeletal muscle of external anal sphincter - defeacation assisted by abdominal contraction and expiration against close glottis
- Contration fo skeletal muscle of external anal sphincter - defeacation delayed - rectal wall gradually relaxes
- Activation of afferents to brain (urge to defeacate) (via pelvic nerves)
- altered firing in efferent to spinal cord
- Relaxation of skeletal muscle of external anal sphincter - defeacation assisted by abdominal contraction and expiration against close glottis
- Contration fo skeletal muscle of external anal sphincter - defeacation delayed - rectal wall gradually relaxes
- altered firing in efferent to spinal cord
Describe the 2 possibilities of the defeactation reflex?
Relation of the skeletal muscle of the external anal sphincter - defection assisted by contraction of abode muscles and expiration against a closed glottis
Contraction of the skeletal muscles of the external anal sphincter - delayed defection , the rectum wall gradually relaxes
Describe the colonic flora?
Contains 500-1000 different species of bacteria - most are beneficial and can be thought of symbiotic
What is the role of the colonic flora?
increase intestinal immunity by competition with pathogenic microbes
promote motility and help maintain mucosal integrity
synthesise vitamin K2 and free fatty acids (from carbohydrate) that are absorbed
activate some drugs (e.g. used in treatment of IBD)
Have a role in enterohepatic cycling of compounds
What conditions does IBD include?
Ulcerative colitis and Chrons disease
What 4 pharmacological agents are included in the treatment of IBD?
Aminosalicylates
Glucocorticoids
Immunosuppressants
Biological agents
Describe the use of aminosalicylates?
Ideal for the longterm maintenance of remission
More useful in UC than crohns
E.g. Sulfasalazine - a combo of 5-ASA linked to sulfaphyridine by an azo bond
Adverse effects - rashes, arthralgias etc
Folic acid supplementation is advised during its use
What is released by the colonic bacteria and what does it do?
5-ASA
It reduces inflammation by inhibiting COX and LOX
Give some other examples that are newer?
Mesalazine - better tolerated than sulfasalazine
Olsalazine
Balsalazide
Describe the use of glucocorticoids in IBD?
Potent anti-inflammatory
Effective in both acute UC and Crohns
Used for ACUTE attack (prolonged use limited by adrenal suppression)
E.g. Prednisolone, Budesonide
Describe the use of immunosuppressants in IBD?
Reserve drugs for severe disease unresponsive to corticosteroids
Steroid sparing effect
Inhibit T lymphocyte function
Slower onset of action
E.g Azathioprine
For mod-severe Crohns and UC
Delayed responses
Can cause bone marrow suppression and hepatotoxicity
Can be continued forum to 5 years
Name some other immunosuppressants in IBD?
Ciclosporin - both UC and Crohns
6- Mercaptopurine
Methotrexate - limited role in severe Crohns
Describe biological agents in IBD?
Monoclonal antibodies Expensive Use is restricted to SEVERE IBD Block the action of TNF alpha Ineffective orally
e.g. IV infliximab
Describe IBS?
It is a common chronic relapsing life long condition
occurs as bouts of diarrhoea, constipation, or abdominal pain.
Treatment is symptomatic with adjustment of diet and anti-diarrhoeals , or laxatives, as required
