Physiology and Pharmacology of the large intestine Flashcards
How big is the large intestine?
Approx 1.5 m long and 6 cm in diameter
What permits the entry of chyme into the large intestine?
The gastroileal reflex
What are the functions of the large intestine?
Absorption of fluids and electrolytes (Na, Cl)
Secretion of electrolytes (K, HCO3)
Formation, storage and periodic elimination of faeces
What are the 4 patterns of motility in the large intestine?
Haustration
Peristaltic propulsive movements
Mass movement
Defaecation
What are haustra?
Saccules caused by the contraction of circular muscle
They are similar to segmentation in function but much lower in frequency
What directions does peristaltic propulsive movement occur in?
Both aboral and oral
oral direction occurs mostly in the ascending and transverse colon which contributes to the long transit time
What is mass movement?
How often does it occur?
What triggers it?
Simultaneous contraction of large segments of the circular muscle of the ascending and transverse colon which drives the faeces into distal regions
This occurs about 1-3 times a day
Typically triggered a meal via the gastrocolic reflex involving gastrin and extrinsic nerve plexuses
Describe the sequence of events which follow after the rectum fills with faecal matter.
The rectal stretch receptors are activated. This activates a) afferents to the spinal cord and b) afferents to the brain- both via the pelvic nerve.
a) afferent signals are sent to the spinal cord via the pelvic nerve, which activates parasympathetic efferents which signal back via the pelvic nerve to the smooth muscle in the rectum. There is contraction of rectal smooth muscle
The internal anal sphincter relaxes.
This can lead to defaecation or a delay in defaecation depending on the efferents from the brain.
b) afferent signals sent via the pelvic nerve to the brain, signalling the urge to defecate.
There are altered efferent impulses sent to the spinal cord depending on whether or not it is convenient to defecate. The spinal cord signals to the external anal sphincter via the pudendal nerve. One outcome is relaxation of the external anal sphincter, and defecation is assisted by abdominal contraction and expiration against a closed glottis. If it is inconvenient to defecate, there is contraction of the skeletal muscle of the external anal sphincter and defecation is delayed. The rectal wall gradually relaxes.
What is constipation?
The presence of hard, dried faeces within the rectum.
What do purgatives/laxatives do?
They increase peristalsis and/or soften faeces causing or assisting evacuation.
When are purgatives indicated?
When straining is potentially damaging to health (e.g. patients with angina), or when defecation is painful (e.g. haemarrhoids), predisposing to constipation.
To clear the bowel out before surgery or endoscopy
To treat drug induced constipation, or constipation in the bed ridden or elderly patients
What are the different types of laxatives and what do they do?
Bulk laxatives: cause the faeces to retain water, and increases the volume of faeces
Stimulant laxatives: Stimulate peristalsis and secrete water and electrolytes
Faecal softeners: soften the faeces
Osmotic laxatives: Cause the stool to retain H20 and increase its volume.
Is the absorption of water an active or a passive process?
What drives this process?
It is a passive process
It is driven by the transport of solutes (particularly Na) from the lumen of the intestine to the bloodstream
What is diarrhoea defined as?
A loss of fluid and solutes from the GI tract in excess of 500ml per day
Does diarrhoea involve the small or the large intestine?
It could involve either
What are potential consequences of diarrhoea?
Dehydration
Metabolic acidosis (HCO3 loss)
Hypokalaemia (K loss)
May be fatal if severe (e.g. cholera)
What does treatment for diarrhoea include?
The first priority is the maintenance of fluid and electrolyte balance
Use of anti-infective agents if appropriate
Use of non-antimicrobial anti-diarrhoeal agents to relieve symptoms
What are the different causes of diarrhoea?
Impaired absorption of NaCl
Non-absorbable or poorly absorbable solutes in the gut lumen
Hypermotility
Excessive secretion
What can cause impaired absorption of NaCl?
Congenital defects
Inflammation
Infection (e.g. enterotoxins from some strains of E.coli and campylobacter)
Excess bile acid in colon
What can cause non-absorbable solutes in the intestinal lumen?
A lactase deficiency
What is an example of a disease which causes excessive secretion in the intestine?
Cholera.
The cholera toxin enters the enterocyte
It enzymatically inhibits the GTPase activity of the alpha subunit of the Gs protein
There is increased adenylate cyclase activity
There is therefore increased concentration of cAMP
cAMP stimulates the CFTR protein
There is then hypersecretion of Cl- with Na and water following
Which membrane transporter does rehydration therapy exploit the activity of?
What does this transporter do?
SGLT1
2 Na bind to the transporter.
The affinity for glucose increases and glucose binds.
Na and glucose translocate from the extracellular to the intracellular space
The 2 Na dissociate and the affinity for glucose falls
Glucose dissociates
The cycle repeats
The absorption of Na and glucose causes accompanying absorption of H2O
What type of drugs have anti-diarrhoeal activity?
Many opiate drugs
What are some of the actions of opiates on the GI tract?
Inhibition of enteric neurones
Decreased peristalsis and increased segmentation
Increased fluid absorption
Constriction of pyloric, ileocolic and anal sphincters
What are the major opiates used in the treatment of diarrhoea?
Codeine
Diphenoxylate
Loperamide
What are the advantages of diphenoxylate and loperamide?
They have low CNS penetration and low solubility in water (therefore there is decreased abuse potential of these drugs)
Which opiate undergoes enterohepatic recycling?
Loperamide
