Digestive and absorptive process of small intestine

Question 1

Explain the digestive functions of the GI tract

Answer 1

Localised to different areas of the gut where:
The optimal pH of enzymes differs
Some enzymes may be secreted as inactive precursors and need enzymatic activation (true of all proteases to prevent digesting yourself)
Some enzymes exist as membrane bound forms (sit on brush border)
Objective: to break macromolecules down into monomer or dimer units for absorption

Question 2

What are the absorptive processes of the GI tract?

Answer 2

Mainly in small intestine, but water also in the colon
Requiring a variety of transport mechanisms specific for particular molecules
If transport is against a gradient, energy must be used (primary or secondary active transport)

Question 3

Give a reminder of the structure of the small intestine

Answer 3

Lots of villi to increase SI.
Single epithelial layer so macromolecules have short diffusions distance.
Goblet cells to secrete mucus to lubricate food.
Enterocytes absorb the nutrients. Stem cells at base of crypt to differentiate at the trans amplifying zone. These cells renew every 3-4 days as they are exposed to pathogens and get damaged.
Lymph system is important for fat absorption. Fat does not go straight into the blood system, they are absorbed into lacteal and then transported out.
Brush border has microvilli where there are lots of transporters (for absorption of solutes) and digestive enzymes which are made by the enterocyte to break down food stuff.

Question 4

What is the unstirred layer in the small intestine?

Answer 4

a layer which does not get churned about even with passing food stuff. This is an added protective layer as food has to diffuse across it

Question 5

What cell junctions are there in the small intestine?

Answer 5

Tight junctions for a barrier function

Question 6

What is the main maintenance function of the small intestine?

What are transporters required for here?

Answer 6

Maintains Na+ gradient which is required by many transporters and created osmotic gradient in intracellular space, which drives water absorption from lumen.

Required for absorption of many solutes (products of digestion).

Question 7

Explain the start of protein digestion

Answer 7

Starts with pepsin and HCl in stomach.
Chief cell release inactive pepsinogen. Becomes active in an acidic environment and formed pepsin. This breaks the proteins into small peptides.
Acidic environment created by parietal cell.

Question 8

What pH is chyme and what’s does it contain?

What else is required in the stomach for digestion of food?

Answer 8

Chyme has a LOW pH and contains
– Solubilised, slightly digested carbohydrates
– Solubilised, partly digested proteins
– Slightly digested fats

• other enzymes are supplied (from pancreas and made by enterocytes)
• pH has to be neutralised,
bile salts needed for fat digestion

Question 9

What is the second stage of protein digestion?

Answer 9

Enterokinase on brush border of duodenal enterocytes activates pancreatic trypsinogen (a specific inactive enzyme) which in turn activates proteolytic enzymes of the pancreas.

• trypsinogen activates trypsin which then can break down the proteins

Question 10

Give the 3 specific enzymes in protein digestion and explain what they do

Answer 10

1) Pancreatic trypsin, elastase & chymotrypsin (endo- peptidases) cleave peptide bonds in protein interior, producing short peptides (chunk up the proteins)
2) Pancreatic carboxypeptidases (exopeptidase) remove amino acids from the carboxyl ends
3) Aminopeptidases (exo- peptidase) on brush border of enterocytes remove amino acids from the amino terminal of peptides

Question 11

How are proteins and amino acids absorbed?

Answer 11

End up near the brush borders with dipeptides. Di and tri peptides are absorbed using H+ transporters. Into enterocytes they are broken down into free amino acids with the enzymes found here to then be absorbed into blood stream.

Free amino acid form can go into the enterocyte via carriers with sodium cotransporter and into the blood stream. They are absorbed via Na+ lumen transporters and exit on the basolateral side.

Question 12

What is infant SI permeable to peptides?

Answer 12

Allows absorption of growth factors and antibodies.

Question 13

What form do we want carbohydrates to be absorbed?

Answer 13

Monosaccharides

Question 14

Explain the 3 places where carbohydrates are digested

Answer 14

1. Salivary amylase:
   optimum pH is 6.8, so some hydrolysis in the mouth
   Swallowed bolus then enters acidic stomach (salivary amylase then stops working here)
2. Pancreatic amylase:
   optimum pH is 7.1
3. Small intestine membrane-bound disaccharides:
   optimum pH valves between 6 and 7

Duodenal pH therefore suitable for (2) and (3)

Question 15

Explain the pancreatic amylase role in carbohydrate digestion

Answer 15

It cleaves straight chains but cannot cleave bonds at branch points.
Produces short oligosaccharides, maltose and maltriose.

Question 16

How does carbohydrate absorption occur?

Answer 16

Apical/luminal side:
- SGLT (Na-linked transporter) for glucose and galactose, active transport
Basolateral side:
- GLUT2 transport for all 3 hexes, facilitated diffusion
- Na pump maintains Na gradient

(Brush border then has enzymes to chop into monosaccharides.

Glucose and lactose are absorbed via a sodium transporter.
Fructose uses GLUT5 to be transported in and then they all use the same transporter to enter the blood.

Energy is provided by the conc gradient of sodium and potassium.)

Question 17

What is required for fat digestion?

Answer 17

Enzyme: mainly pancreatic lipase but some gastric lipase

• colipase
• bile salts
• right pH
  all needed for digestion in duodenal lumen
• beta-lipoprotein
  inside enterocyte, to package lipid for export as chylomicrons

Question 18

What are the 4 steps in fat digestion?

Answer 18

1. emulsification of fat in lumen (requires bile salts) - turns large lipid droplet into small ones
2. action of lipase to convert TGs to MGs and 2xFAs
3. formation of micelles (made of MGs, FAs, bile salts, etc)
4. diffusion of micelles to epithelial cell brush border

Question 19

What are the 4 steps in fat absorption?

Answer 19

1. trans-membrane transport of the free FAs and MGs (by diffusion through the lipid core)
2. Intracellular resynthesis of triglyceride (in the SER)
3. incorporation of the TG into chylomicrons, together with beta-lipoprotein, cholesterol, etc (packaging them into chylomicrons using these things)
4. efflux of the chylomicrons on the basolateral side of the cell, into nearby lacteals. Absorption of capillaries does not happen in the intestine, instead does into the base lateral side.

Question 20

Explain the enterohepatic reciruculation of bile salts

Answer 20

Gall baller contracts, bile salts go into duodenum.
Then want to reabsorb them into liver.

Some loss of Bile salts in faeces but the liver makes more.

95% of bile salts are reabsorbed, mainly in terminal ileum.
Transported back to liver via portal vein and re-extracted by hepatocytes to be re-exported in bile juice.
Can be turned over 3-4 times during a large meal.

Question 21

Explain the net water absorption in the colon

Answer 21

net water absorption (following Na+ down ATP osmotic gradient)
• water and Na reabsorption stimulated by aldosterone (under hormonal control)
resident microflora are prevented from crossing epithelial barrier, but they help to produce vit. K and folic acid which are absorbed here

Given by sodium potassium ATP pump. Drag of sodium out of cell and water will follow.
Aquaporins allows water to pass through centre of cell but also get transport of water through tight junctions both driven by this pump.

Question 22

What are the 3 other functions of the GI tract?

Answer 22

Minerals
specific mechanisms for absorption of mineral ions such as Ca2+, Fe2+ etc – see nutrition lectures

Vitamins
specific mechanisms for B & C vitamins – see nutrition
• fat-soluble vitamins generally absorbed with lipids, in SI and colon

Drugs
Absorbed best when non-ionised, both in the SI (right pH) and colon
• limited absorption of a few drugs (e.g. aspirin) across gastric mucosa

Question 23

What are causes of malabsorption?

Answer 23

failure to absorb vit B12
failure to digest macromolecules in chyme due to:
• interruption of the enterohepatic circulation of bile salts
• failure to deliver pancreatic enzymes
• poor co-ordination of gastric emptying with delivery of pancreatic & biliary

Question 24

What are solutes that can fail to be reabsorbed and explain these?

Answer 24

• lactose, because brush border lactase is absent, and lactose remains in
disturbance in erythropoiesis, resulting in much fewer, but macrocytic rbc
lumen (alactasaemia)
• lipids because of lack of beta-lipoprotein required to make chylomicrons
• lipids because of failure of lipid digestion
• sufficient water because it is retained in lumen accompanying increased solute load (stops sodium gradient so retains water in lumen)
• sufficient water because of increased salt & water secretion caused by bacterial infection (stops sodium gradient and retains water in lumen)
vit B12, folate & Fe2+ leading to anaemias

Question 25

What leads to failure to absorb vit B12?

Answer 25

failure to absorb vit B12
failure to digest macromolecules in chyme due to:
absorption in ileum (specific transporter recognises the vit B12 only when complexed with intrinsic factor)

Question 26

What does insufficient intrinsic factor result from?

Answer 26

• gastric atrophy,
• an autoimmune condition - patient mounts an immune response against own intrinsic factor &/or the parietal cell result:
- Disturbance to eyrthropoesis, resulting in much fewer, but microcytic rbc

Question 27

Explain the failure to absorb iron

Answer 27

• absorption in SI, requiring specific transport mechanisms
• assisted by previous acid pH in stomach , which helped maintain the fe3+ ions in a soluble state for later absorption

Result:
Failure to make sufficient haemoglobin, resulting in microcytic rbc
Relevance to dentists?
you could spot this - pale gums due to anaemia, + changes to tongue surface & ‘glossitis’ (sore/burning’ tongue) in some cases

Question 28

Explain osmotic diarrhoea and secretory diarrhoea

• causes
• affects

Answer 28

osmotic diarrhoea as a result of malabsorption (not absorbing solutes so leave water in lumen so affects faeces)
• incomplete absorption leaves an increased solute load in the SI lumen
• water stays with it (osmotic effect)
outcome:
• much increased volume of lumenal contents, stimulating peristalsis
• undigested fats may also have a laxative effect
• many of the partially digested food stuffs are fermented in the LI (by local microflora resulting in formation of gases)
outcome:
• much increased volume of lumenal contents, stimulating peristalsis
• undigested fats may also have a laxative effect
local microflora), resulting in formation of gases (e.g. H2), distension (pain)
many of the partially digested food stuffs are fermented in the LI (by local microflora), resulting in formation of gases (e.g. H2), distension (pain)

Secretory diarrhoea in response to bacterial infection
e.g. Vibrio cholerae and Escherichia coli toxins increase the secretory activity of intestinal crypt cells (see lecture APS 56
Sodium gradient is affected and water cannot be absorbed correctly.
Also:
Diarrhoea secondary to intestinal mucosa damage
e.g. coeliac disease (autoimmune condition mainly of SI caused by an adverse reaction to gluten)
e.g. Crohn’s disease (inflammatory condition, mainly affecting ileum & colon)