structure and function of the colon

structure of the large intestine

approx. 1.5m long

arranged into haustra which gives the colon its segmented appearance

comprise of the caecum, colon (ascending, transverse, descending), rectum, anal canal

functions: absorb remaining nutrients, absorb water, store and eliminate stool

organization of the colonic mucosa

colonic epithelial cells arise from stem cells within the crypt

• transporting enterocytes

• goblet cells

• enteroendocrine cells

• Paneth cells - less numerous than in the SI.

Lamina propria contains nerves and immune cells that regulate epithelial function

Peyer patches are less numerous than in the small intestine

colonic mucosa functions

• absorption and secretion

• form a barrier

• communication with bacteria

colonic enteroendocrine cells

EEC population of the large bowel in generally less diverse than in the small intestine

I cells, S cells, G cells, M cells are absent

enteroendocrine cells - enterochromaffin cells

largest population of EEC cells in the colon

store and release 5-HT (serotonin)

primarily function as sensors of the luminal content

are activated by stretch and nutrients as a food bolus moves through the lumen

released 5-HT stimulates motility and increases local fluid secretion

not to be confused with enterochromaffin-like cells (ECL) in the stomach

enteroendocrine cells - L cells

sense nutrients (e.g. glucose) in the lumen

release glucagon-like peptide 1 (GLP-1)

GLP-1 stimulates insulin secretion from the pancreas

GLP-1 also sends satiety signals to the brain

organization of the colonic muscle

colonic muscularis consist of an inner circular layer and outer longitudinal layer of smooth muscle

However, the longitudinal layer is organized into 3 discontinuous longitudinal bands, known as taeniae coli (bands of the colon)

the bands of the taeniae coli are lightly shorter than the underlying circular layer causing the intestinal wall to bunch up into its haustral appearance

types of colonic motility

haustral movements

• slow segmenting movements occurring every 25 mins

• serve to mix/churn the contents and increase exposure to the epithelium

Peristalsis

• propels the bolus forward towards the sigmoid colon and rectum

• occurs slowly in the large intestine to allow maximal absorption

mass movements

• specialized peristaltic contraction occurring only in the colon

• occur 3-4 times a day (after meals)

• clears the colon by forcing material towards the rectum

• can cause rectal distension and trigger the defecation reflex

gastrolienal and gastrocolic reflexes

before food arrives into the large intestine, it has been readied

presence of food in the stomach induces neural (cholinergic) and hormonal (gastrin and CCK) stimuli that induce

Gastrolienal reflex

• peristalsis of the terminal ileum

• relaxation of the ileocecal valve

Gastrocolic reflex

• mass movement along the colon

• induces the urge to defecate soon after a meal

serve to prepare the lower intestine for the arrival of a new meal

Ileocecal junction

when food reaches the end of the ileum, it enters the large intestine through the ileocecal valve

peristaltic contraction of terminal ileum forces chyme through the valve into the caecum

contraction of the caecum causes the ileocecal valve to close - prevents reflux of colonic contents into ileum

approx. 2L of material pass into caecum/day

at this point the chyme contains mostly water, indigestible food particles (fiber), and bile acids

bacteria and digestion - fiber

dietary fiber cannot be metabolized by digestive enzymes

fiber can be fermented by gut bacteria to short chain fatty acids (SCFAs) e.g. acetate, propionate, butyrate

SCFAs are not found at high concentrations in the caecum (70-140mM) and decrease along the colon - are primary determinants of pH along the colon

Enter epithelial cells by active and passive transport and are used as the primary source of fuel for epithelial cells (60-70%)

bacteria and digestion - vitamins

vitamins are organic compounds required of life - must be taken in the diet because humans do synthesize enough

some vitamins are produced through bacterial metabolism in the large intestine

• vitamin K - required for blood coagulation and bone metabolism. deficiencies include bleeding disorders, osteoporosis

• Vitamin B12 (cobalamin) - required for hematopoiesis and healthy nerves. deficiencies cause anemia and damage to nervous system (fatigue, depression, memory loss)

• vitamin B-7 (biotin) - required for cell growth, production of fatty acids an fat/amino acid metabolism,. Deficiencies cause neurological symptoms, hair loss, conjunctivitis and dermatitis.

colonic absorption - water

water movement in the intestine occurs along osmotic gradients

driven by electrogenic Na⁺ absorption

the rectum

final segment of the intestinal tract (15cm) from the end of the sigmoid colon to the anal canal

mucosa largely resembles the colon, but the crypts and lined almost entirely with goblet cells.

function: to temporarily store feces

is normally empty but fills up when a mass movement pushes stool from the sigmoid colon

defecation reflex

defecation involves both involuntary and voluntary reflexes

Peristalsis and mass movement force feces into the rectum, triggering stretch receptors

stretch receptors activate a spinal reflex that stimulates peristalsis and relaxes the internal anal sphincter while contracting the external sphincter

increased pressure in the rectum sends a signal to the brain and we feel the urge to defecate

defecation reflex - delay & defecation

if the urge is not acted on, continued voluntary contraction of the external sphincter and high pressure triggers reverse peristalsis - feces are returned to the sigmoid colon. More water is absorbed to decrease fecal volume until the next mass movement triggers the reflex again

if a voluntary signal volume is sent back along the pudendal nerve, the external anal sphincter relaxes, the rectum contracts, and material exits through the anal canal

Anal canal has stratified squamous epithelium to pretect against abrasion.

feces - composition

70% water and 30% solid

30% of the solid matter consists of bacteria

30% consists of indigestible food matter

10-20% is cholesterol and other fats

10-20% is inorganic substances (e.g. calcium phosphate and iron phosphate)

2-3% protein

cell debris shed from the mucosa (epithelial cells and leukocytes)

bile components (e.g. bile acids; bilirubin)

diarrhea

an illness that causes you to pass waste from your body very frequently an in liquid rather than a solid form

=> 3 loose or liquid stools per day for 3 days

classified as acute (<14 days) or chronic (>14days)

constipation

the condition of being unable to easily pass waster from your body

=< 3 bowel movements a week

associated with hard lumpy stools and straining

causes of diarrhea

diarrhea occurs when there is too much fluid in the stool.

amount of fluid depends on rate of fluid absorption vs. rate of secretion

diarrhea occurs when too little absorption or too much secretion or increased peristalsis

treatment of diarrhea

ensure hydration and use medication if necessary:

• anti-motility agents e.g. loperamide

• antimicrobials e.g. rifaxamin

• anti-inflammatory drugs

• alternative medicines e.g. charcoal, probiotics

constipation symptoms

• < 3 stools/week

• hard/dry, small stools

• abdominal pain/swelling

• bight blood on the stool

• hemorrhoids

long term constipation symptoms

affects quality of life - stress, diminishes overall sense of wellbeing

leads to cardiovascular, endocrine and immune problems

in elderly people, chronic damage to the mucosal membrane can lead to development of colon/rectal cancer

causes of constipation

usually occurs when peristaltic action is diminished - stool mooves too slowly and becomes hard and dry

• diet: insufficient intake of dietary fiber, insufficient H₂O intake

• medication: diuretics, opioids

• obstructions: strictures, tumors

• neurological/hormonal conditions: hypothyroidism, multiple sclerosis, parkinson’s disease

• psychosomatic constipation: based on anxiety e.g. new job, exams

• IBS: 1/3 IBS patients have IBS-C

treatment of constipation

change of lifestyle - change of diet ( more fiber), increased levels of exercise

laxatives - bulk forming (fiber), osmotic (lactulose), stimulant (senna, Psyllium)

drug therapy - amitiza (softens stool by stimulating fluid secretion)

role of the colon in drug absorption

the colon does not have the capacity of the small intestine for drug absorption

is equally as permeable to lipophilic drugs in ascending colon

also has several carrier-mediated transport systems that can act as targets for hydrophilic drugs

both locally-targeted (ulcerative colitis) and systemic (protein and peptidase drugs) delivery of drugs can be achieved

colonic delivery strategies

prodrugs: inactive drugs are metabolized by bacteria in the colon

colon specific biodegradable delivery systems - encapsulate a drug in polymer matrices which can only be degraded be bacterial enzymes

times release systems

pH sensitive coatings - polymers breaks down basic Ph in ileum, thus providing targeted drug delivery to the colon

factors affecting colonic drug absorption

pH: basic drugs are better absorbed from the distal than proximal colon

viscosity of contents: only the ascending colon is fluid enough for diffusion of drugs to occur

first pass effect: drugs absorbed from the colon will enter the EHC and pass through the liver

transit time: slow transit gives more time for absorption

bacterial metabolism: can increase or decrease metabolism

rectal route of delivery advantages

relatively large dosage form can be accommodated

safe and convenient for elderly and young patients

drug dilution is minimized as the residual fluid volume is low

relatively empty

degradative enzymes are practically absent

first pass elimination by the liver is avoided

useful if there is nausea, vomiting in unconscious patients, if there is upper GI disease, if there is an unpleasant taste