1. Large Intestine Physiology Harvey Davies & Sean Botham Peer Support

2. What is the large intestine composed of? [4]  A combination of the: o Cecum o Colon o Rectum o Anal canal

3. What are the functions of the large intestine? [3]  3 main functions o Extract sodium and water from the luminal contents o Make and store faeces o Move faeces towards the rectum

4. Why is water absorption in the large intestine so important? [3]  1500ml of water per day enters the large intestine  100ml is lost in faeces  An imbalance can lead to constipation or diarrhoea

5. How is water absorbed in the large intestine? [4]  Na + /H + exchanger on luminal surface  Electrogenic Na + transporter also moves sodium in  Water follows transcellularly  Na + released via Na + /K + - ATPase on the basolateral membrane

6. What structures allow the large intestine to move it’s contents? [3]  Taeniae coli – three bands of smooth muscle  Circular smooth muscle  Haustra – bulges caused by the taeniae coli  The ileocaecal valve prevents backflow

7. How does the large intestine move it’s contents? [4 - 2+2]  Haustral contractions (mixing) o Combined contractions of the taeniae coli and the circular muscle layer o Causes the colon to budge into segments called haustrae  Mass movements (propulsion) o Propel the luminal contents from the beginning of the transverse colon to the sigmoid colon o Are a series of modified peristaltic events o Occur 1-3 times a day

8. What is the defecation reflex? [3]  Rectum normally empty of faeces  The defecation reflex is a response to distension of the rectal wall  Mediated by mechanoreceptors  Can be self-induced via the Valsalva Manoeuvre  Rectoanal inhibitory reflex

9. What are the steps involved in the defecation reflex? [6]  Contraction of the rectum  Relaxation of the internal anal sphincter  An initial contraction of the external anal sphincter  Increased peristaltic activity in the sigmoid colon  Relaxation of the external anal sphincter  Expulsion of faeces

10. Constipation What is it? < 3 bowel movements/week. Straining >25% of bowel movements/sensation of hard stool. Tenesmus (sensation of incomplete bowel evacuation). Signs/Symptoms? Painful defaecation. Hemorrhoids/anal fissures. Distended & diffusely tender abdomen with enhanced bowel sounds.

11. Purgatives – speed things up! Bulk laxatives: increase the volume of non-absorbable residue. Example = Methylcellulose. Osmotic laxatives: increase stool H 2 O content. Example = Milk of Magnesia. Faecal softeners: alter faecal consistency. Example = Ex-Lax. Stimulant purgatives: increase GI motility. Example = Bisacodyl or Senna.

12. Bulk Laxatives Example – Methylcellulose. MOA – Polysaccharide polymers that are not broken down by normal digestive process (1). Retain water in GI lumen (2), softening and increasing faecal bulk (3) and promoting increasing motility (4). Acts for 1-3 days. (Contra) Indications – good first choice in constipation & IBS. S/E = may decrease absorbance. Stomach cramps.

13. Osmotic Laxatives Example – Milk of Magnesia (Magnesium Sulphate + Magnesium Hydroxide). MOA – By osmosis, maintain an increased volume of fluid in GI tract (1). This accelerates small intestine transit (2) and an abnormally large volume of fluid entering the colon (3). Distension (4) leads to purgation (5). Potent, rapid action for a watery evacuation (1-2 hours). (Contra) Indications – bowel prep for surgery. Avoid in small children & poor renal function. S/E – dehydration, electrolyte depletion.

14. Faecal Softeners Example – Ex-Lax. MOA – Surface-eating compounds that act similar to detergents and produce softer faesces. Slow acting, 3-5 days. (Contra) Indications – fissures, piles ( soft faesces = less likely to rupture ). S/E – few. Some stomach/intestinal cramps.

15. Stimulant Purgatives Example – Senna. MOA – passes unchanged into colon where colonic bacterial action releases free anthracene derivatives (1). These are absorbed and have a direct effect on the myenteric plexus (2), decreasing tone and haustrations leading to less mixing and water absorption (3) and an overall purgative effect (4). (Contra) Indications = very common use. Avoid in breast- feeding mothers. S/E – N+V, diarrhoea, cathartic colon, can appear in breast milk.

16. Cathartic Colon What is it? Anatomical & Physiological changes in colon with chronic use of stimulant laxative (>3 times/week for 1 year). What happens? Laxative dependency to defecate. Tachyphylaxis (need higher doses to achieve therapeutic effect). How does it present? Incomplete faecal evacuation. Steatorrhoea. Fluid and electrolyte imbalance.

17. Diarrhoea – 4 Types Secretory diarrhoea Osmotic diarrhoea Motility-related diarrhoea Inflammatory diarrhoea

18. Treatment of Diarrhoea 1.Oral Rehydration Therapy Treats dehydration. Isotonic solution of glucose & NaCl (glucose enhances Na+ absorption and so H 2 O. 2.Anti-infective agents (if required). 3.Anti-motility agents – Loperamide. Act on µ-opioid receptors in the myenteric plexus. Increases tone & rhythmic haustral contractions of colon, but diminishes propulsive activity. Pyloric, ileocaecal & anal sphincters are contracted. Increased tone of haustral contractions  increased mixing & opportunity to reabsorb Na + & H 2 O  production of harder stool.