2. OBJECTIVES
Describe the mechanisms, localization and regulation of colonic sodium
absorption.
Describe the mechanisms mediating colonic bicarbonate and potassium
transport.
Describe the role of dietary fiber in promoting colonic motility.
Describe the factors contributing to intestinal and colonic gas composition and
the consequences of an altered colonic microflora.
Describe the role of short chain fatty acids in colonic sodium absorption and in
both colonic and body energy metabolism.
Describe the related roles of fluid malabsorption in the small intestine versus
colon on the potential to cause diarrheal disease.
Describe the normal regeneration of the colonic epithelium from stem cells,
and how this process is changed if a stem cell becomes cancerous or in the
presence of inflammation.
3. Large Intestine:
Extends from ileocecal junction to anus
Consists of cecum, colon, rectum, anal canal
Movements sluggish (18-24 hours)
6. Functions of the Large Intestine
Reabsorb water and compact material into feces
ELECTROLYTE ABSORPTION
Absorb vitamins produced by bacteria
Store fecal matter prior to defecation
NB: Most of the absorption occurs in the proximal half of the colon
(absorbing colon), the distal colon (storage colon) functions to store
faeces until time of excretion
7. Na+ absorption
Mucosa of the large intestine has a large capability for Na absorption
(active)
Electrical dy/dx created by this absorption causes Cl absorption as well
Na ions are far more absorbed here than in the small intestine
Aldosterone enhancement
increasing expression of the basolateral NaK ATPase and luminal Na+ ion
channels.
This Na and Cl absorption creates an osmotic gradient which in turn
causes absorption of water
8. Electrogenic Na+ absoption
Is by epithelial sodium channels (ENaC)
LUMEN SIDE
Inhibited by amilorides and diuretics
Na under an electrochemical gradient
Na absoption is accompanied by Cl as well via the CFTR
Basolateral Na/K pump
Aldosterone increases these channels
9.
10. Electroneutral transport
Bulk transport of Na by luminal Na/H & Cl/HCO3 exchanger
Na transport in ascending colon is mainly by electroneutral transport
while in the desending colon its electrogenic (via which channels and
under the enhancement of what hormone?)
Parrallel Na/H and Cl/HCO3 exchanger on the colonic epithelial cells
Transport of Na is coupled via changes in intracellular pH and[CL]
Basolateral Na/K ATPase generates the driving force for the luminal Na
by lowering intracellular Na
Regulated by Na depletion
12. Regulation of Na Absorption
1. feedback regulation
Ocuurs on ENaCs
Na has a negative impact on the activity of the channels
This occurs due to changes I intracellular Na
Increase in [Na] in the colon cells downregulates and eventually endocytosis of ENaC
2 Steroid-Dependent Regulation of Ion TransporT
upregulated by glucocorticoid and mineralocorticoid hormones.
This leads to enhanced Na1 absorption and K1 secretion
aldosterone induces only electrogenic absorption
upregulation of the activity of other transport proteins like the basolateral
Na1-K1-ATPase by aldosterone is another mechanism by which aldosterone regulates Na1
absorption.
13. Fluid malabsorption disorders
Cholera
Cholera bacillus produces a toxin that enters the cells
toxin binds to the alpha unit of the Gs inhibiting the GTPase activity
Prolonged stimulation of adenylyL cyclase increases cAMP
Increased Cl secretion
Decreased absorption of Na and Cl
Water and electrolytes
14. Absorption of short chain fatty acids
a)In parallel with the absorption of NaCl, SCFA
are absorbed by the colonic epithelium usually by non ionic diffusion
SCFA are produced during fermentation of dietary fibers by colonic bacteria.
b)an additional SCFA/HCO3 exchange mechanism
Cl absorption is stimulated by increased HCO3 production during SCFA metabolism and
stimulation of the apical Cl2/HCO3 2 exchanger.
Absorption of SCFA not only serves as an additional energy supply for colonic epithelial
cells, but has also a significant impact on NaCl absorption
acidification of colonocytes and activation of apical Na1/H1 exchangers
15. Cont….
Absorbed SCFAs are metabolised and contribute to calories
In addition, they exert a trophic effect on on colonic epithelial
cells
They also combat inflammation
They are absorbed in part by ab exchange mech for H+,
thereby helping to maintain acid-base equilibrium
They also promote absorption of Na+
16. Role of dietary fibre
Reduces risk of colon canser
Increased fecal weight
Shortened transit time
Dilution of colonic contents
Stimulation of colonic microbial growth
lower your risk of developing haemorrhoids
solidify the stool because it absorbs water and adds bulk to stool
17. Motility of the colon
Movements include: 1. segmental contraction
2. peristaltic waves
Segmental contraction mix up the contents of the colon,
exposing them to the mucose, thence facilitating absorption
Peristaltic –propel towards the rectum
18. Movement in Large Intestine
Mass movements
Common after meals
Local reflexes in enteric plexus
Gastrocolic: Initiated by stomach
Duodenocolic: Initiated by duodenum
Defecation reflex
Distension of the rectal wall by feces
Defecation
Usually accompanied by voluntary movements to expel
feces through abdominal cavity pressure caused by
inspiration
20. Absoprtion in the large intestine
About 1500 ml of chyme pass thru the ileolcecal valve each day
Most of the water and electrolytes in the chime are absorbed in the colon
The large intestine can absorb up to 5-8 liters of fluid and electrolytes each
day
21. Defacation
Distension of the rectum with faeces initiates contractions
SNS-excitatory, PNS-inhibitory…in internal(involuntary) anal sphincter
External anal sphincter-skeletal(which nerve)
The urge to defacate occurs when the rectal pressure is about 18mmHg
At >55mmHg , reflex defecation
Normally there is a 90 degree anorectal jxn which inhibits defecation,in combination
with puborectalis
With straining abdominal muscles contract puborectalis muscles relax; anorectal jxn is
reduced to 15 degrees
22. Defecation Reflex
1. Distension of the rectum.
2. Stimulation of the stretch
receptors in the rectum.
3. A. Short reflex: Stimulation of
myenteric plexus in sigmoid colon
and rectum.
B. long reflex: stimulation of
parasympathetic motor neurons
in sacral spinal cord.
C. stimulation of somatic motor
neurons.
4. Increased local peristalsis.
Relaxation of internal anal
sphincter and contraction of
external anal sphincter.
23. Gastrocolic reflex
Distension of the stomach
Contractions of the rectum, the desire to defacate
It can be amplified by an action of gastrin on the colon
Because of the response, defeaction after meals
commonly occurs in children
Same as duodenocolic reflex
24. Composition of faeces
about 75% of fecal weight is made up of water. The other 25% is
composed of solid matter which contains :
1.Undigested fiber and solidified components of digestive juices (30%)
2.Bacteria (30%)
3.Fat (10% to 20%)
4.Inorganic matter (10% to 20%)
5.Protein (2% to 3%)
25. Color and odour
Brown…….largely due to bilirubin
Which is converted to urobilin and stecobilin to give give stool its typical color
Odour
differs among people
Largely influenced by the foods eaten
Due to bacterial action
The actual odoriferous products includeindole, skatole, mercaptans, and hydrogen
sulfide
27. Secretions of the Large Intestine
Mucus Secretion.
The mucosa of the large intestine has many crypts of Lieberkühn.
Absence of villi.
The epithelial cells contain almost no enzymes.
Presence of goblet cells that secrete mucus (provides an adherent
medium for holding fecal matter together).
Stimulation of the pelvic nerves from the spinal cord can cause
marked increase in mucus secretion. This occurs along with increase
in peristaltic motility of the colon.
During extreme parasympathetic stimulation, so much mucus can
be secreted into the large intestine that the person has a bowel
movement of ropy mucus as often as every 30 minutes; this mucus
often contains little or no fecal material.
28. Roles of the mucus
protects the intestinal wall against excoriation,
it provides an adherent medium for holding fecal matter
together.
protects the intestinal wall from the great amount of bacterial
activity that takes place inside the feces, and,
finally, the mucus plus the alkalinity of the secretion (pH of 8.0
caused by large amounts of sodium bicarbonate) provides a
barrier to keep acids formed in the feces from attacking the
intestinal wall.
30. constipation
pathological decrease in bowel movements
However, many normal humans defecate only once every 2–3 d, even though
others defecate once a day and some as often as three times a day
the only symptoms caused by constipation are slight anorexia and
mild abdominal discomfort and distention.
Some causes of constipation include:
1. Antacid medicines containing calcium or aluminum
2. Changes in your usual diet or activities
3. Colon cancer