Physiology lecture 29

Digestion & absorption in the small intestine​

Synopsis​

• Structure and function of the small intestine​

• Carbohydrate digestion & absorption​

• Protein digestion & absorption​

• Fat (lipid) digestion & absorption​

Microanatomy of small intestine​

Intestinal surface area is enhanced by finger-like villi and crypts​

villi and crypts

crypts important for secretions - also have stem cells at bottom

have good blood supply and lymph to allow absorption

microvilli and epithelial cells

Functions of the small intestine​

• Digestion​ - Luminal, membrane and cytosolic​

• Nutrient absorption​ e.g. carbohydrates, proteins, fats, vitamins, iron​

• Drug absorption​

• Electrolyte absorption​ - NaCl​

• Water absorption​ ~7 litres/ day​

• Secretion​ - Fluid, NaCl​, through Crypts

Key points in carbohydrate digestion and absorption

• Carbohydrate in diet mainly polysaccharides​

• Carbohydrate only absorbed as monosaccharides​

• Luminal digestion of starch-type polysaccharides​ - Amylases​

• Membrane digestion by disaccharidases ​- Maltase, sucrase-isomaltase, lactase​

• Absorption of monosaccharides in the small intestine

Average daily carbohydrate intake in England​

starch most abundant in diet

cellulose - from plants - fermented by colonic bacteria to allow SCFA production and gas production

Sucrose most abundant disaccharide

Carbohydrate Digestion​​

amylase - endo enzyme - cannot break end bonds so is only a disaccharidase

Absorption of Monosaccharides​ - Na+

via conc gradients in particular sodium can allow for carb absorption

Absorption of Monosaccharides​

• Only monosaccharides absorbed​

• Apical Membrane​:

• SGLT1 (glucose, galactose)​ - Na+ coupled, secondary active transport​

• GLUT5 (fructose)​ - Facilitated diffusion​

• Basolateral membrane​ - GLUT2​ (Facilitated diffusion)

Movement of sodium at apical membrane and Na+K+ pump at BL membrane allow for transport of monosaccharides

Key points in protein digestion and absorption​

• Digestion of proteins​

• Luminal digestion by gastric and pancreatic proteases​

• Membrane digestion by brush-border peptidases​

• Cytosolic digestion within epithelium of small peptides​

• Absorption in small intestine​

• Amino acids​

• Peptides​

• Intact protein absorbed in antigenic quantities(especially in neonate) but nutritionally unimportant - influence in immune system

Protein digestion​

• Gastric pepsin​ - start of protein digestion (Luminal)

• 10-20% digestion​

• Endopeptidase​

• Pancreatic peptidases​ (luminal)

• e.g. trypsin​

• Endopeptidases and exopeptidases​

• Short peptides (2-6 AAs) and free amino acids (~30%)​

• Membrane and cytosolic peptidases​

• Endo, exo or dipeptidases​

• Many different types​

• Free amino acids

Absorption of peptides & amino acids​ - microclimate

secondary AT allows for protein absorption - using H+ ions

Absorption of peptides & amino acids​

peptide absorption

• Utilises acid microclimate ​

• H+-coupled di/tripeptide transport (H+ gradient maintained by NHE3 a sodium/H+ exchanger.)

• Approx. 50% of protein absorption​

• Followed by cytosolic peptide digestion or export by unknown basolateral transporter (different from PepT1)​

• Peptide carrier also important for drugs​ -

• Angiotensin-converting enzyme (ACE) inhibitors​

• b-lactam antibiotics​

• Prodrugs (Val-acyclovir)

? = unknown transporters - but must be present to exchange AAs and absorb them into body

Amino acid absorption​

• Numerous types of amino acid transporters​

• Neutral, cationic, anionic​

• Overlapping specificity​

• Apical Membrane​

• Mainly coupled to ion uptake (e.g. Na+)​

• Secondary active transport​

• Accumulation within epithelial cells​

• Basolateral Membrane​

• Mainly facilitated diffusion

Key points in fat (lipid) digestion & absorption​

• Low water solubility​

• Solubilisation - by Bile salts​

• Digestion​ - then Pancreatic lipase​

• Absorption ​- Passive​

• Re-esterification of fatty acids ​- Maintains gradient for absorption ​

• Transport to blood​ - Chylomicrons via lymph system

Dietary lipids​

• Triglycerides ​(majority of dietary lipids)

• Triesters of glycerol and long-chain fatty acids (C16, C18) [triglycerides]​

​

• Phospholipids​

• substitute 1 fatty acid chain with phospho-ester of organic base(e.g. choline gives lecithin)​

• ​

• Short chain fatty acids ​

• minor – dairy

• also some formed from colonic bacteria

lipid digestion and absorption

stage 1 lipid digestion

• Emulsification (Stage 1)​

• Begins with chewing, grinding and mixing of food​

• Fat droplets, 1microm​ - gives enzymes enough substrate for digestion

• Increases oil-water interface area​

• Stabilised by bile salts & phospholipids

stage 2 LD

• Digestion (Stage 2)​

• Gastric (15%) and pancreatic lipases​ - Work at oil-water interface​

• Co-lipase​ - Prevents inhibition of lipases by bile acids​

• Triglycerides to 2 fatty acids & a monoglyceride

ALLI - weight loss drug that inhibits pancreatic lipase (is a derivative of lipstatin) - less lipid digestion so likely to experience diarrhoea and bacteria in colon use this and release lots of gas

Micelles​

• Polymolecular aggregates, 5nm​

• Monoglyceride, fatty acids & bile salts​

• Cholesterol & fat-soluble vitamins (A, D, E, K)​

• Close approximation to enterocyte microvilli for absorption

following stages

• Diffusion down gradient (Stage 3)​

• Driven by re-esterification of fatty acids to triglycerides within epithelial cells (Stage 4) ​

• Released across basolateral membrane as chylomicrons (<1microm) (Stage 5)​

• Enter blood via lymph system

• Fat soluble vitamins (A, D, E, K) follow same route of absorption

LOs

• Describe the processes involved in the digestion of fats, carbohydrates and protein​

• Give an account of the absorption mechanisms for fats, carbohydrate and protein digestion products