Physiology And Pharmacology Of The Large Intestine

Question 1

What are the 3 main functions of the large intestine?

Answer 1

1. Extract Na+ and water from the chyme in its lumen
2. Make and store faeces
3. Move faeces towards rectum to be expelled

Question 2

What is the epithelial cells of the large intestine called, what do they secrete and why?

Answer 2

Goblet cells secrete alkaline mucus which serves to:
Protect epithelium from acid, abrasion and bacterial activity
Provide an adherent medium for holding faecal matter together

Question 3

How much water and solids do humans take in a day and how much of this is excreted?

Answer 3

1.2 L of water and 800g of solid ingested a day
Salivary, gastric, pancreatic and intestinal secretions & bile add to this too so there is roughly 7L of water moving into GI tract
Vast majority is reabsorbed into the circulation (mostly in SI, but LI too)
= only 100ml of water is lost and 50g of solid excreted

Question 4

How is water reabsorbed in the jejunum?

Answer 4

Movement of Na+ from lumen into epithelial cell via a Na+-glucose linked transporter (SGLT1)
Na+ is pumped across basolateral membrane against concentration gradient via a Na+/K+ ATPase
Water will follow due to the osmotic gradient through the cells and into the blood
Some water can go between epithelial cells straight into the blood via leaky tight junctions

Question 5

Explain the characteristics of tight junctions across the intestines.

Answer 5

Tight junctions between intestinal epithelial cells are leaky whereas usually they do not let anything pass through them
The duodenum tight junctions are the most leaky whereas as you go down the GI tract the colon has the tightest tight junctions

Question 6

What are the 2 routes water can take through intestinal cells into the bloodstream?

Answer 6

Transcellular (through cells) if tight junctions are very tight i.e. in the colon
Paracellular (between cells) if tight junctions are leaky i.e. in the duodenum

Question 7

How is water reabsorbed in the colon?

Answer 7

Na+ H+ ion exchanger can be used
OR
Electrogenic Na+ channel
This gets Na+ from the lumen into the epithelial cell
Na+ K+ ATPase gets Na+ from the cell into the blood
Water follows due to the osmotic gradient
Absorbs 1.4 L out of the 1.5L presented to it, only loosing 100ml so its very active in absorbing water

Question 8

What is the ileocaecal valve and what does it do?

Answer 8

One-way valve guarded by a sphincter that seperates the terminal end of the ileum from the caecum
It prevents back-flow of faecal contents from the colon
It controls the rate at which ileal chyme enters the colon so the colon can handle it
Regulated by neural and hormonal mechanisms

Question 9

Why does the colon have motility and what 2 types of movement does it show?

Answer 9

Motility facilitates efficient absorption of water and salts and permits the orderly evacuation of faeces
Movement of the colon is either haustral contractions (mixing) or propulsive (mass movements)

Question 10

Explain haustral contractions of the large intestine.

Answer 10

The colon has longitudinal muscle aggregated into 3 bands called taeniae coli. Combined contraction of the taeniae coli and circular muscle layer causes the colon to bulge into segments called haustrae. These localised contractions mix the contents of the ascending and first part of transverse colon with intestinal secretions. This facilitates salt and water reabsorption.

Question 11

Explain propulsive movements of the large intestine.

Answer 11

Mass movements propel the luminal contents from the beginning of the tranverse colon to the sigmoid colon. There is vigorous contraction of smooth muscle layers of segments that stay contracted for some time meaning content is rapidly squeezed towards the rectum. This part takes 10-30 minutes, stops and starts several hours later again. Thus, there is a series of modified peristaltic events that occur 1-3 times a day. There is the urge to defecate once the rectum starts to fill.

Question 12

What is the gastrocolic reflex?

Answer 12

Mediated by gastrin and extrinsic autonomic nerves
Initiates propulsive mass movements in colon
Pushes colonic contents into rectum triggering defaecation reflex
Most evident after 1st meal of day

Question 13

Why are the rectum and anal canal normally empty?

Answer 13

Rectum and anal canal normally empty of faeces because angular corner before rectum and sphincter stop it filling up via resistance
Anal canal has an internal smooth muscle sphincter (involuntary) and a external skeletal muscle sphincter (voluntary)

Question 14

What is the defaecation reflex?

Answer 14

Reflex response to distention of rectal wall mediated by mechanoreceptors, it consists of:
Contraction of rectum
Relaxation of internal anal sphincter
Initial contraction of external anal sphincter
Increased peristaltic activity in sigmoid
Relaxation of external anal sphincter
Expulsion of faeces

Question 15

Explain why we have voluntary control over defaecation.

Answer 15

Brain centres can override reflex signals and keep external anal sphincter closed which allows voluntary control
Involves the valsalva manoeuvre

Question 16

What are the 4 steps of the valsalva manoeuvre?

Answer 16

1. Full inspiration followed by forced expiration against a closed glottis caused the diaphragm to move down
2. Abdominal and thoracic muscles contracted
3. Increased pressure in the abdomen forces faecal contents into rectum
4. Defecation reflex is initiated

Question 17

What is the composition of faeces?

Answer 17

75% water and 25% solid matter (dead bacteria, fat, inorganic matter, protein, undigested material i.e. bile pigment and sloughed epithelial cells)
Faeces is brown due to derivitives of bilirubin
It has a odour due to products of bacterial action

Question 18

What does the large intestine harbour a large proportion of anaerobic bacteria?

Answer 18

Provides immunity against common bacteria
Converts bilirubin to urobilinogens
Forms secondary bile acids
Degrades digestive enzymes
Digests mucus
Synthesizes certain vitamins like K
Metabolizes undigested polysaccharides Therefore, oral antibiotics that kill bacteria will disrupt these functions

Question 19

What are the 2 types of drug classes used to treat issues with GI motility?

Answer 19

Purgatives
Anti-diarrhoel agents
Act mainly on large intestines as its important for GI transit time

Question 20

What are the factors that affect bowel habit?

Answer 20

Age
Physiology
Diet
Social and cultural influences 
May indicate disease

Question 21

How do purgatives work?

Answer 21

Accelerate transit through the intestine so used to alleviate constipation

Question 22

What is constipation?

Answer 22

Infrequent or difficult evacuation of faeces Infrequent meaning < or equal to 3 times per week
Difficulty can mean straining > 25% of bowel movements of subjective sensation of hard stools
Can get sensation of incomplete bowel evacuation

Severe cases will cause faecal impaction featuring symptoms of vomiting, tender abdomen and paradoxical diarrhoea (soft stool from SI bypasses impacted matter in colon)

Question 23

What are the causes and treatments of constipation?

Answer 23

Causes: dietary, hormonal, anatomical, side effects of medication (e.g. opioids) and illness/disorder
Treatments:
1st line - change diet (increase fluid/fibre) and exercise habits
2nd line - purgatives
3rd line - other medical intervention depending on cause

Question 24

What are the signs and symptoms of constipation?

Answer 24

Type 1 and 2 on Bristol Stool Chart 
Stool is hard
Difficult and painful to pass stool
Infrequent urge to void
Haemorrhoids and anal fissures 
Later stages may cause abdomen distention, tenderness, cramps and increased bowel sounds

Question 25

What are the signs of underlying problems in relation to constipation?

Answer 25

Weight loss and anaemia with constipation may suggest colon cancer
Alternating constipation/diarrhoea in otherwise healthy patients may suggest IBS
Painful defaecation in patients with anorectal disease
May arise as side effect of medication e.g. antidepressants and opioids

Question 26

What are the 4 types of purgatives and how do they work?

Answer 26

Bulk laxatives increase volume of non-absorbable residue
Osmotic laxatives increase stool water content
Faecal softeners alter faecal consistency
Stimulant purgatives increase GI motility
In order of usage from 1st line to last line

Question 27

How do bulk laxatives work?

Answer 27

They are polysaccharide polymers that are not normally broken down by digestion so they retain water in GI lumen, softening and increasing faecal bulk which will stimulate mechanoreceptors and promote increased motility .
E.G.s plant gums like spaghula husk (Fybogel) and methylcellulose (Citrucel)
Act in 1-3 days (dissolved in water and taken by mouth)
Good 1st choice in constipation and IBS

Question 28

How do osmotic laxatives work?

Answer 28

They are poorly absorbed solutes like saline purgatives, macrogols and lactulose so remain in lumen and via osmosis, maintain an increased volume of fluid in GI tract accelerating SI transit resulting in abnormally large volume of fluid entering colon. This leads to distention which leads to purgation.

Question 29

What are the characteristics of saline and macrogol osmotic laxatives?

Answer 29

1. Saline purgatives: magnesium sulphate and magnesium hydroxide, potent rapid action (1-2hrs), watery evacuation, good for bowel prep prior to procedure
2. Macrogols (1st line nowadays): inert polymers of ethylene glycol, sequester fluid in bowel, treats faecal impaction in children and used for long-term management of chronic constipation

Question 30

How does the osmotic laxative lactulose work?

Answer 30

Semi-synthetic dissacharide of fructose and galactose that cannot be digested in SI so moves to LI -> colonic bacteria convert it to 2 component monosaccharides which are poorly absorbed in LI -> fermentation yields lactic acid and acetic acid which function as osmotic laxatives pulling water into colon lumen bringing about purgation (alike lactose intolerance mechanism)

Question 31

What are the characteristics of osmotic laxative, lactulose?

Answer 31

2nd line if macrogol is ineffective
Act within 1-3 days
Used in chronic constipation, hepatic encephalopathy and especially useful for negating constipating effects of opioid drugs

Question 32

How do faecal softeners work and what are their key characteristics?

Answer 32

E.G.s docusate and arachis oil enema
They are anionic surfactants which lower surface tension at oil-water interface allowing water or fats to enter the stool softening faecal matter.
Act slowly i.e. 3-5 days
Used in constipation and fissures/piles

Question 33

How do stimulant purgatives work and what are their key characteristics? Talk about 2 examples.

Answer 33

E.G. Bisacodyl which is usually given as suppository that stimulates rectal mucosa resulting in mass movements and defaecation in 15-30 minutes. Only used short-term but useful with opioid induced constipation
E.G. Senna which contains derivatives of anthracene combined with sugars to form glycosides - it passes unchanged into colon where bacterial action release free anthracene derivatives which are absorbed and directly act on myenteric plexus in the ENS (wall of GI tract). This stimulates longitudinal muscle causing pulses of propulsive movements but decreased mixing and absorption of luminal contents.

Question 34

What is diarrhoea?

Answer 34

Frequent watery, loose bowel movements
Involves increased GI motility and secretion but decreased absorption so there is fluid and electrolyte loss
Can be caused by infectious agents, toxins, anxiety and drugs
Principal cause of death in malnourished infants due to inability to rehydrate

Question 35

What are the 4 different types of diarrhoea?

Answer 35

Secretory - increased active secretion of ions or inhibition of absorption but no structural damage e.g. cholera
Osmotic - loss of water due to heavy osmotic load e.g. maldigestion in Coeliac disease where nutrients remain in lumen pulling water into it
Motility-related - high GI motility decreasing time available for nutrient/water absorption e.g. diabetic neuropathy
Inflammatory - damage to mucosal lining/brush border causing passive loss of protein-rich fluids and decreased ability to absorb lost fluids e.g. bacterial, viral and parasitic infections, autoimmunity or IBD

Question 36

What are the 3 main types of treatment for diarrhoea?

Answer 36

Maintenance of fluid/electrolyte balance (especially Na+ and K+) e.g. oral rehydration
Anti-diarrhoeal agents which decrease motility
Anti-infective agents if the cause is an infectious agent

Question 37

How do oral rehydration therapies treat diarrhoea?

Answer 37

They are a isotonic or hypotonic solution of glucose and NaCl so they exploit the ability of glucose to enhance Na+ absorption via the SGLT1 transporter and hence water. This rehydrates patients as water is pulled into the cells and then the blood.

Question 38

How do anti-motility agents work in the treatment of diarrhoea?

Answer 38

These are opioids like codeine and loperamide (Imodium) however, loperamide is relatively selective to GI tract as they act on m-opioid receptors in the myenteric plexus and does not cross the BBB. This increases tone and rhythmic haustral contractions/mixing of colon but diminishes propulsive activity so there is increased absorption of intestinal contents making faeces more solid. The pyloric, ileocaecal and anal sphincters all become contracted.

Question 39

What are anti-motility anti-diarrhoeals used for?

Answer 39

Symptomatic treatment of acute uncomplicated diarrhoea in adults ADJUNCT to rehydration therapy
However, chronic use leads to constipation, abdominal cramps, dizziness and sometimes paralytic ileus