Physiology and Pharmacology of the Large Intestine

Question 1

How long does it take for material to pass through the large intestine?

Answer 1

Around 18-24 hours

Question 2

What is entry into the large intestine usually permitted by?

Answer 2

The gastroileal reflux through the ileocaecal sphincter which acts as a one way valve

Question 3

What is the gastroileal reflux stimulated by?

Answer 3

Gastric distention

Question 4

What controls the opening etc of the ileoceacal valve?

Answer 4

The vagus nerve - sympathetic and enteric neurones

Question 5

What does the ‘one way valve’ (ileocaecal sphincter) do?

Answer 5

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

Question 6

What are the major functions of the large intestine?

Answer 6

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

Question 7

What does HCO3- do?

Answer 7

HCO3- neutralises acid produced by bacterial fermentation

Question 8

Describe the mass movements of the large intestine?

Answer 8

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

Question 9

Describe haustration of the large intestine?

Answer 9

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

Question 10

Describe the defecation reflex of the large intestine?

Answer 10

A spinal reflex triggered by distention of the rectum

Question 11

Describe the ‘steps’ in the defecation reflex?

Answer 11

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

Question 12

Describe the 2 possibilities of the defeactation reflex?

Answer 12

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

Question 13

Describe the colonic flora?

Answer 13

Contains 500-1000 different species of bacteria - most are beneficial and can be thought of symbiotic

Question 14

What is the role of the colonic flora?

Answer 14

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

Question 15

What conditions does IBD include?

Answer 15

Ulcerative colitis and Chrons disease

Question 16

What 4 pharmacological agents are included in the treatment of IBD?

Answer 16

Aminosalicylates
Glucocorticoids
Immunosuppressants
Biological agents

Question 17

Describe the use of aminosalicylates?

Answer 17

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

Question 18

What is released by the colonic bacteria and what does it do?

Answer 18

5-ASA

It reduces inflammation by inhibiting COX and LOX

Question 19

Give some other examples that are newer?

Answer 19

Mesalazine - better tolerated than sulfasalazine
Olsalazine
Balsalazide

Question 20

Describe the use of glucocorticoids in IBD?

Answer 20

Potent anti-inflammatory
Effective in both acute UC and Crohns

Used for ACUTE attack (prolonged use limited by adrenal suppression)

E.g. Prednisolone, Budesonide

Question 21

Describe the use of immunosuppressants in IBD?

Answer 21

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

Question 22

Name some other immunosuppressants in IBD?

Answer 22

Ciclosporin - both UC and Crohns
6- Mercaptopurine
Methotrexate - limited role in severe Crohns

Question 23

Describe biological agents in IBD?

Answer 23

Monoclonal antibodies 
Expensive 
Use is restricted to SEVERE IBD
Block the action of TNF alpha
Ineffective orally 

e.g. IV infliximab

Question 24

Describe IBS?

Answer 24

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

Question 25

What 3 types of drugs might you use to treat IBD?

Answer 25

Antispasmodic
Laxative
Anti motility