Digestion and absorption

How can enzymes be secreted in the gut?

o   Some enzymes may be secreted as inactive precursors

o   Some enzymes exist as membrane bound forms

What is the main role of digestion?

-              break down macromolecules into monomer dimer units for absorption

Describe the structure of the villi

o   The villi consist of a single epithelial cell layer

o   Most of the cells at the villi are enterocytes, which are the main cells required for nutrient absorption

o   Goblet cells produce mucus for defence and lubrication

o   Enteroendocrine cells control gut secretions and the motility of the gut

o   The villi are highly vascularised

o   Lacteal network, which is used for the absorption of lipids

o   The crypt base (bottom of villi) is where the stem cells are which generate the epithelial cells

Where is the main site of water absorption?

The colon

Describe the structure of enterocytes

-              Each villus is lined by enterocytes and microvilli

-              Microvilli increase the surface area for absorption

-              Enterocytes have tight junctions between them, which helps in controlling what is absorbed

-              Many different transporters are present on the microvilli, which are attached to glycocalyx

how do enterocytes draw out water?

-              Presence of Na+/ATP pumps Na+ out of the lumen and into the interstitial space, so water is drawn out from between the cells

o   Water is also draw through the cells via aquaporins

o   Na+/ATP pump maintains low Na+ concentration in the epithelial cell, which is required by many transporters

o   This low Na+ gradient creates an osmotic gradient in the interstitial spaces, which drives water absorption from the lumen

How does protein absorption occur?

-              Starts with pepsin and HCl in the stomach (HCl from parietal cells)

-              Chief cells secrete pepsinogen (any enzyme with -inogen) at the end is in its inactive form

-              Low pH required via HCl, which allows the conversion of pepsinogenpepsin

-              Stomach releases chyme into the duodenum

-              Enterokinase on the brush border of duodenal enterocytes activates pancreatic trypsinogen, which activates proteolytic enzymes of the pancreas

-              This forms trypsin, which is the active form, and this digests the protein

-              In the lumen or unstirred layer of the enterocyte, there are exopeptidases (pancreatic carboxypeptidases), which cleave single amino acids from the carboxyl terminal

-              Endopeptidases (pancreatic trypsin, elastase and chymotrypsin) then hydrolyse the amino acid sequences from the middle, allowing more exopeptidases to act on them

-              Aminopeptidases (exopeptidases) remove amino acids from the amino end

-              These break down amino acids into mono, di and tri peptides

What is chyme?

o   Chyme has a low pH

o   Contains solubilised, slightly digested carbohydrates

o   Solubilised, partly digested proteins (solubility is important as only when these things are soluble can enzymes act on them)

o   Slightly digested fats

o   Intrinsic factor – enables vitamin B12 to be absorbed in the small intestine

How are amino acids absorbed?

o   Amino acids are absorbed via Na+ linked luminal transporters and exit on the basolateral side

o   Di and tri peptides are absorbed via H+ linked luminal transporters and then hydrolysed, exiting as amino acids on the basolateral side (absorption not as good as amino acids)

How does protein absorption occur in infants?

-              the small intestine wall of the baby becomes permeable to peptides, allowing for absorption growth and antibodies from the colostrum/first milk

What is the role of cellulose?

-              Cellulose is a polysaccharide and cannot be digested, hence forming part of the dietary fibre

What are disaccharides?

-              sucrose (glucose + fructose), lactose (glucose + galactose), maltose (glucose + glucose)

What are monosaccharides?

glucose, fructose, galactose

How does carbohydrate digestion occur?

-              Carbohydrate digestion begins in the saliva via salivary amylase

o   Optimal pH is 6.8 so some digestion can occur here where the swallowed bolus then enters the acidic stomach

-              Pancreatic amylase has an optimal pH of 7.1

-              Small intestine membrane-bound disaccharidases have an optimal pH between 6 and 7

-              Duodenal pH is between 2 and 3

-              So, carbohydrate digestion mostly occurs through pancreatic amylase

How does pancreatic amylase digest carbohydrates?

o   Can cleave straight chains but not at branch points

o   Produces short oligosaccharides, maltose (disaccharides) and maltriose (trisaccharide)

o   Further digestion of these another other disaccharide (lactose, sucrose) occurs via brush border enzymes at the edge of the lumen

How does carbohydrate absorption occur?

o   Apical/luminal side – SGLT (Na+ linked transporter) for glucose, galactose – active transport/co-transport

o   On the basal side connected to the capillary side, glucose etc can diffuse into the blood stream down it’s concentration gradient

o   Fructose has it’s own transporter GLUT5 for entry into the epithelial cell and enters the blood via GLUT2

o   All hexoses enter the blood via GLUT2 through facilitated diffusion

What enzymes and compounds are required for fat digestion?

-              Uses mostly pancreatic lipase as well as some gastric lipase

-              In the duodenal lumen, colipase, bile salts and a specific pH is required

-              Beta-lipoproteins are required inside enterocytes – these package lipids for export as chylomicrons

Why is fat digestion difficult and how is this overcome?

-              Fats are not water soluble, making it difficult for enzymes to hydrolyse them so, they need to be emulsified to increase the surface area for enzymes to act on them

How does fat digestion occur?

-              Bile salts emulsify lipid droplets, increasing the surface area for the enzymes to act on in the lumen

-              Pancreatic lipase acts on the emulsified droplets

-              This causes the triglycerides to form monoglycerides and fatty acids

-              Micelles are formed – these are made of monoglycerides, fatty acids and fatty acids

-              These can diffuse across the lipid bilayer at the epithelial cell brush border

-              Transmembrane transport of the free fatty acids and monoglycerides by diffusion through the lipid core

-              Intracellular resynthesis of triglycerides in the smooth endoplasmic reticulum

-              Incorporation of the triglyceride into chylomicrons together with beta-lipoprotein, cholesterol etc

-              This enters the lacteal system and then the blood

How does fat absorption occur?

-              Bile salts are reabsorbed at the bottom of the ileum (just before the colon)

o   These then travel along the portal vein and the liver extracts the bile salts, making a circulation of bile salts or storing them in the gall bladder

o   Bile salts can be turned over 3-4 times during the digestion of a single meal

o   5-10% loss per day via faeces, which is compensated by de-novo synthesis in the liver

How does water absorption occur in the colon?

-              Net water absorption, which follows the Na+ concentration gradient

-              Water and Na+ reabsorption is stimulated by aldosterone

-              Aquaporins present on the luminal membrane would also increase the permeability of water

-              Resident microflora are prevented from crossing the epithelial barrier

o   These help to produce vitamin K and folic acid, which are also absorbed here

What state do drugs have the best absorption?

Non-ionised mostly in small intestine or colon

Why may there be failure to digest macromolecules in the chyme?

o   Interruption of the enterohepatic circulation of bile salts

o   Failure to deliver pancreatic enzymes

o   Poor co-ordination of gastric emptying with delivery of pancreatic and biliary secretions

Why may there be failure to absorb lactose?

Brush border lactase absent so it remains in lumen

Why may there be failure to absorb lipids?

-              lack of beta-lipoprotein so, no chylomicrons

failure of lipid digestion

Why does diarrhoea occur?

Failure to absorb sufficient water because it is retained in the lumen accompanying increased solute load

Failure to absorb sufficient water because of increased salt and water secretion caused by bacterial infection

What is a failure to absorb B12, folate and Fe2+?

Anaemia

Why may anemia occur?

o   Failure in ileum – its specific transporter recognises vitamin B12 only when it is complexed with its intrinsic factor

o   Insufficient intrinsic factor results from gastric atrophy or an autoimmune condition (immune attack against own intrinsic factor or the parietal cell)

o   This results in disturbances in erythropoiesis, resulting in low RBC and macrocytic RBC

o   Failure to absorb Fe2+ in small intestine

§  Requires specific transporters and is assisted by stomach pH (maintains Fe2+ ions in a soluble state for later absorption)

What is osmotic diarrhoea?

-              due to malabsorption, which leaves an increased solute load in the small intestine lumen (water stays in lumen)

Why may diarrhoea occur?

-              Volume of lumen increased, increasing peristalsis

-              Undigested fats may have laxative effect

-              May be lots of partially digested foods, which become fermented in the large intestine by local microflora, resulting in the formation of gases = distension and pain

-              Diarrhoea can occur in response to small intestine damage – eg coeliac disease or Crohn’s

What is secretory diarrhoea?

-              in response to bacteria infection