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Summary

  • Many nutrients are consumed as complex molecules (carbohydrates, lipids, proteins) that need to be enzymatically broken down into smaller absorbable molecules.
  • Additional substances (ions, minerals, vitamins) do not require such digestion.
  • All molecules then need to be transported across the lining of the gastrointestinal wall and into the bloodstream or lymphatics as appropriate.
  • Once it gets into the enterocyte, a micronutrient must still be transported across the basolateral membrane of the enterocyte before it enter the inside of the individual

Small intestine tissue structure

Structure of the small intestine
  • Inner surface contains 'circular folds' (folds of Kerckring, calvulae conniventes) on which villi are positioned.
  • Increases the SA by a huge amount, so that you don't really need 50% of your gut (very efficient)

Absorptive surfaces are “maximized”

  • Villi contain absorptive vasculature and lymphatics, and are lined by the enterocytes.
  • Each enterocyte is lined by a "brush border" containing microvilli.
  • Actin filaments allow for movement.

Inside the villus

Inside the villus
  • Blood supply and lymph for absorption of nutrients. Lymph is squished out of that sac because the villus is mobile

Major functions of the small intestine

  • Absorption of nutrients is the exclusive function of the small intestine (only place nutrients are absorbed; water and salts absorbed elsewhere as well)
    • Carbohydrates, protein and fats
    • Ions, vitamins, water etc.
  • BUT, most nutrients require digestion by luminal and brush border enzymes to enable transport to bloodstream or lymph


Secretions of the pancreas

  • Endocrine (blood) and exocrine (gut lumen)

Composition of pancreatic juice

  • Two distinct components of pancreatic juice:
    • Watery alkaline secretion rich in HCO3‐
    • Digestive enzymes
  • Pancreatic HCO3‐ acts to neutralise the acidic stomach contents as they enter the small intestine
  • The pancreatic enzymes complete the digestion of carbohydrates, protein and fats
    • They are broken down into small constituent molecules that can be absorbed.
  • Similar to producing acid in stomach, but in reverse

Activation of pancreatic enzymes

Activation of pancreatic enzymes
  • Enzymes are packaged as inactive precursors
  • Enteropeptidase is immobilised in the membrane (pretty much safe, won't float around chewing up cells)
  • Now the luminal content is chyme and the gruel has activated enzymes mixed within it

Digestive enzymes

  • A little bit of lipase in the mouth make it taste nicer (if short chains) or rancid (if long chains)

Absorption

  • Process by which molecules cross barriers imposed by the gut lining/wall to enter the bloodstream
  • Absorption is aided by both the secretions and motility of the GIT - more on motility in lecture 2
  • The physical and chemical nature of the nutrients determines how they are absorbed across the GIT wall
  • Some substances are absorbed without digestion
    • Water, ions, vitamins
  • Most nutrients have to be broken down before absorption

Mucosal barrier to absorption

  • Things have to diffuse through a thick layer of mucus before they get to the enterocyte - protects your intestine from a lot of rancid materials

Carbohydrate in the diet

  • 60% complex carbohydrates - starch
  • 30% disaccharides - sucrose and lactose
  • 10% monosaccharides - glucose, fructose
  • Monosaccharides can be absorbed across the small intestine epithelium, therefore for the most of the carbohydrate in the diet digestion has to take place before absorption

Digestion of carbohydrate

  • Luminal digestion by salivary and pancreatic amylases converts starch to disaccharides
  • Brush border digestion by disaccharidases converts disaccharides to monosaccharides:
    • sucrose --sucrase--> glucose + fructose
    • lactose --lactase--> glucose + galactose
    • maltose --maltase--> glucose + glucose
  • Swallowed amylases are digested by the stomach
  • The amylases in the middle of a bolus from chewed food can digest a little bit, but it's not necessary later on. (It's good to chew your food, but it's not required)
  • Memorise the following more complicated slide showing how the molecules cross the membrane

Absorption of carbohydrates

The monosaccharide products of carbohydrate digestion (glucose, fructose, galactose) are absorbed by the small intestine in a two step process.

  1. Across the apical cell membrane
    • Glucose and galactose
      • Na+/glucose co‐transporter (SGLT1)
    • Fructose facilitated sugar transporter (GLUT5)
  2. Across the basal cell membrane
    • Facilitated sugar transporter (GLUT2)

LOL why not just have GLUT2 on both membranes? IDKYNOT

Because. Science. http://memegenerator.net/instance/21963994

Monosaccharide absorption

  • There are different apical transporters for different sugars while the basolateral transporter is common
  • Don't get as much glucose into your blood as you'd think, because you need sodium along with glucose to get taken in.

Abnormalities of CHO digestion or absorption

  • Lactose Intolerance (an example): Genetic or acquired condition where the enzyme lactase is deficient
  • Lactose = “milk sugar”
  • Lactose --lactase--> glucose + galactose (lactase not sufficiently available in lactose intolerance)
  • Lactose accumulates in the gut
    • acts as an osmolyte (osmotic laxative ‐ traps water in the lumen)
    • acts as nutrient for bacteria
    • accumulation of water and gas lead to irritation, bloating and diarrhoea
  • Controlled by dietary modification or exogenous enzymes
  • Not an allergy!
  • Lactose intolerance: not very high levels of lactase enzyme (when a kid, you can handle a lot of milk, but lactase production drops off over time as you get older)
  • Lactose allergy: IgE, immune system

Protein in the diet

  • The body's protein requirements:
    • Adult - 0.6 g/kg body weight/day
    • Child - 3-4 g/kg body weight/day
  • Average diet - 90 g protein/day
    • 10-30 g from GIT secretions including the proteases produced by the pancreas
  • A lot of the protein in your diet is your own protein (recycling)
  • Chemotherapy:
    • Hair falls out (hair follicles are quickly dividing)
    • Bone marrow
    • GIT
  • GIT epithelium cells have 5-10 day turnover (a lot of this cellular debris is recycled; broken up by lumen and reabsorbed)

Digestion of protein

Digestion and absorption of proteins occurs through 4 major pathways:

  1. Luminal proteases from the stomach and small intestines can hydrolyse proteins to small peptides and amino acids
  2. Brush border aminopeptidase digests the small peptides to single amino acids
  3. Peptides are absorbed and broken down to individual amino acids by cytoplasmic peptidase
  4. Small peptides are absorbed and cross directly into the blood stream.
  • 1 makes up 30%, 2-4 make up 70%

Absorption of amino acids

Amino acids are absorbed into the blood stream in two steps:

  1. Across the apical cell membrane
    • Na+ dependent amino acid co-transporter
    • H+ dependent peptide co-transporter
  2. Across the basal cell membrane
    • Mainly an amino acid co-transporter which is Na+ independent (uses other ions)

Apical transport of amino acids

  • Amino acids
    • At least 7 transport systems in the apical membrane
      • For groups of amino acids (e.g. acidic, basic, beta-amino acids)
    • The pre-dominant amino acid transporter is the Na+ dependent amino acid co-transport
      • Driven by the inward directed Na+ gradient
  • Small peptides (3-6 amino acids)
    • Small peptide uptake occurs via the H+/peptide cotransporter (PepT1)
      • An active process driven by the H+ gradient
      • Most small peptides are broken down in the enterocytes by cytoplasmic peptidases to single amino acids

Apical absorption of amino acids

Basal transport of amino acids

  • 90% of the absorbed amino acids are transported across the basal membrane and into the circulation
  • The remaining 10% is used by the enterocyte for intracellular protein synthesis
  • At least 5 amino acid transporters are present in the basal membrane
    • 3 mediate transport out of the enterocyte
    • 2 absorb amino acids into the enterocyte
  • Most basal amino acid transporters are not dependent on the Na+ gradient (uses other ionic gradients)

Absorption of amino acids

Absorption of water

Break up starch into 60 molecules -- 60 times more osmotically active (need water from your plasma to go through the enterocyte into the gut.

  • Diffusion
    • Driven by osmotic gradients (bi-directional)
    • Osmotic gradient can be established by absorption of ions into the intercellular spaces (helped by the existence of tight junctions)
  • Should be noted that water movement across the gut wall is a continual and bi-directional process

Water intake

  • Cholera - secretory diarrhoea. It causes your cells to secrete fluid, and you can't reabsorb all of it, so you die of dehydration
  • SI absorbs most of the water. The large intestine has a large capacity for absorption, but the SI can out-secrete the LI's absorption capacity.

Absorption of ions

  • Na and Cl come and go as they please. Ca and Fe are different.
  • Sodium
    • Co-transport with nutrients (glucose, amino acids)
    • Neutral co-transport with Cl-
    • Na+/H+ exchanger
    • Epithelial Na* channel (ENaC)
  • The gradient is provided by the Na+/K+ ATPase on the basolateral surface of the enterocyte

Absorption of calcium ion

Factors in Ca2+ absorption

  • Mainly absorbed in the duodenum
  • About half of Ca++ absorption is regulated while the remaining half is unregulated
    • Regulated involved calcium binding proteins (CaBPs)
    • Unregulated involves paracellular absorption
  • Oxalate in some green leafy vegetables binds to Ca++ and prevents its uptake

Absorption of iron ion

  • Requires the binding protein ferritin and transferrin
  • Iron release from enterocytes is also regulated according to needs/plasma levels (liver hormone hepcidin)
  • Iron tends to make insoluble salts, or be in unabsorbable forms

Absorption of vitamins

  • Fat soluble:
    • A, D, E and K
    • Absorbed along with lipids due to solubility in lipid droplets, micelles, chylomicrons
  • Water soluble
    • B-complex and C
    • Require transport proteins (active transport or facilitated diffusion)
    • Vitamin B12
      • Requires "protection" by a protein called intrinsic factor (IF) secreted from the gastric parietal cells
      • The "IF-B12" complex is transported to the ileum where absorption occurs. Abnormalities in this process lead to pernicious anaemia.
  • Pernicious anaemia - no intrinsic factor, lack of B12, affects rapidly dividing cells

Fats in the diet

  • Average diet of fat is 60-90 g/day which is approximately 40% of the daily energy intake
  • Fat ingested in the form of:
    • triglycerides (90%)
    • cholesterol esters (<5%)
    • phospholipids (lecithin) in small amounts (<5%)

Digestion of fats

  • Fats and lipids are hydrophobic and therefore not soluble in the aqueous lumen of the GIT.
  • Fats must be modified before being capable of passive diffusion.
  • The central process in digestion of fats is:
  1. Emulsification into fine oil droplets by the bile salts produced by liver and released into the duodenum
  2. Hydrolysis catalysed by lipases produced by the salivary gland, gastric mucosa and the pancreas

Emulsification

Enterohepatic circulation

  • Less absorption of bile --> more production of bile

Solubilisation of lipids

Enzymes for hydrolysis of fats

Absorption of fat

  • Lipases break fats down into fatty acids, monoglyceride, cholesterol and lyso-lecithin
  • Traditionally these were thought to cross the cell membrane by simple diffusion
  • Recently, several transporters have been identified that facilitate uptake of fats
    • Eg fatty acid transport protein-4

Absorption and exocytosis of fats

  • Can't get into blood vessels (tight junctions; blobs are huge); can get into lymph vessels (very leaky)

Re-packaging of lipids

  • Incorporation into chylomicron for lymphatic transport
  • Chylomicrons are lipoproteins, part protein and part lipid (e.g. low or high density -LDLs or HDLs)

Objectives

  • Understand the enzymatic processes required for effective digestion of carbohydrate, lipid and protein
  • Understand the transport and carrier mechanisms required for nutrient movement across the gut wall
  • Appreciate that the "design" of the small intestinal absorptive surface maximises the transport capacity
  • Understand the barriers presented to molecules during transport, or absorption, of molecules across the GIT wall
  • Understand how the physical and chemical nature of the nutrients impacts on these barriers