This document summarizes digestion and absorption in the gastrointestinal tract. It describes how nutrients like carbohydrates, proteins and fats are broken down into smaller molecules through hydrolysis. Carbohydrates are broken down into monosaccharides, proteins into peptides and amino acids, and fats into fatty acids and monoglycerides. Absorption occurs through active transport, passive diffusion, and endocytosis across the intestinal epithelium. The small intestine has adaptations like villi and microvilli that increase its surface area for absorption. Water and electrolytes like sodium and chloride are also absorbed through the intestines.

1. CHAPTER 66 – DIGESTION AND ABSORPTION IN THE
GASTROINTESTINAL TRACT
Guyton and Hall
Basis for Digestion – Hydrolysis:
 Digestion involves the breakdown or hydrolysis (addition of h20) of nutrients to
smaller molecules that can be absorbed in small intestine.
 Carbohydrates  monosaccharides
 Proteins  small peptides + amino acids
 Fats  2 monoglycerides + Fatty Acids
Types of Digestion
 Luminal or cavital
digestion
- Occurs in lumen of
GI tract
- Enzymes from
salivary glands,
stomach, pancreas
- Pancreatic enzymes
can do all
 Membrane or
contact digestion
- Enzymes on brush
border of
enterocytes
Anatomical Basis for Absorption
 Total surface area of small intestine is 250-400m2
 Small intestine – 4m long
 Folds of Kerckring = 3-fold
 Villi = 10 fold
 Microvilli = 1000-fold

2. Life cycle of Small Intestinal Enterocytes
 Villi house self-renewing population of epithelial cells with a 5-day turnover.
 Cell types in villus include:
- Secretory cells
- Endocrine cells
- Goblet cells
- Mature absorptive epithelial cells
 Cells in enterocyte lineage divide and differentiate as they migrate up crypts,
becoming mature absorptive cells.
 Enterocytes are shed into lumen to become part of ingesta to be digested and
absorbed.
Mechanisms of Absorption
 Four mechanisms are important in transport of substances across intestinal
cell membrane
1. Active transport
- Primary
- Secondary (Co-transport, counter-transport)
2. Passive Diffusion
3. Facilitated Diffusion – carrier mediated
4. Endocytosis
Sodium Electrochemical Gradient
 Single most important process in small intestine to make absorption of
nutrients possible is establishment of electrochemical gradient of sodium
across epithelial cell boundary of lumen (apical membrane).
Sites of Absorption
 Stomach – ethanol, NSAIDs, Aspirin
 Duodenum and Jejunum – nutrients, vitamins, various ions, h20 and
electrolytes.
 Ileum – bile salts and vitamin B12, major clinical significance
 Colon – h20 and electrolytes
 Rectum – drugs such as steroids and salicylates

3. Water Absorption:
o Water flows by osmosis
 Towards the hypertonic solution
 Generally H2O follows Na+ ions (but not always)
o Facilitated by aquaporins – channel proteins
specific to water
Principle Sites of H2O Absorption:
o Jejunum
 Na/K-ATPase sets up negative Na
concentration gradient within cell.
 Na causes SGLT1 to import Na & Glucose.
 As Na flows in, H2O follows.
 Basal GLUT2 transporter: Glucose à
interstitium.
 Clinical relevance: for treatment of severe
dehydration, a solution of Na & Glucose
optimises H2O absorption.
o Ileum
 Na/K-ATPase sets up negative Na conc.
grad. within cell.
 Draws Na through Na/H-Antiporter
 H+  lumen
 HCO3  lumen to balance electrical
charge
 Cl-  cell  interstitium to balance
Na+.
o Proximal Colon
 Na/K-ATPase sets up negative Na
conc. grad. within cell
 Draws Na through ion channel in apical membrane.
 Excess K leaks back to interstitium through leakage channels.

4. Absorptive Pathway of Nutrients
 A nutrient must cross 8 barriers to be absorbed by blood or lymph
1. Unstirred layer
2. Glycocalyx
3. Apical cell membrane
4. Cytoplasm of enterocyte
5. Basolateral cell membrane
6. Intercellular space
7. Basement membrane
8. Wall of capillary or lymph vessel
Digestion
 Carbohydrates
 Proteins
 Fats

5. DIGESTION OF CARBOHYDRATES
 Starch digestion
1. Begins with α-amylase in saliva (5% digestion in mouth, upto 40% in
stomach)
2. Continues in small intestine with pancreatic amylase
3. Final digestion occurs at brush border
 Lactose and sucrose – digestion only occurs at brush border
 The final products of carbohydrate digestion are all monosaccharides, mostly
glucose.
lactose = galactose + glucose
Sucrose = fructose + glucose
Maltose & Glu-polymers = glucose
80% - glucose
10% - fructose
10% - galactose
Absorption of Carbohydrates
 Absorption is rate limiting step in carbohydrate assimilation
 Glucose and galactose – secondary active transport
- Compete for membrane carrier (SGLUT-1)
- Energy from NA+-K+ATPase
 Fructose – facilitated diffusion (GLUT-5) [passive transporter]
- Does not require energy
- Requires concentration gradient
 Hexose transporters
- 2 distinct groups of hexose transporters are classified based on energy
dependence
 Transport hexoses down concentration gradient via facilitated diffusion
(GLUT1, GLUT2, GLUT3, GLUT4, GLUT5)
 Transport hexoses against concentration gradient using sodium
electrochemical gradient via secondary active transport (SGLUT1).
Abnormalities of Carbohydrate Assimilation
 Lactose intolerance
Symptom – abdominal cramps, bloating, diarrhea, and flatulence
Diagnosis – feed lactose – look for glucose in plasma
Cause – absence of brush border lactase.
 Lack of glucose/galactose carrier – rare
- Diagnosed at birth
- Feed fructose

6. Carbohydrate Absorption in GI Tract:
• Approx 200-600g/day
• About 50% of energy needs – met by carbs.
• Complex carbs – best for slow-release energy.
• Energy Content: 16kJ/g (measured in Joules)
Carbohydrate Digestion:
• Mouth:
o Salivary α-Amylase:
 Breaks down starch polysaccharidesàsmaller chunks of a few units
 Requires correct pH – works in mouth but not stomach
 From parotid & submandibular glands.
• Small Intestine Lumen:
o Pancreatic α-Amylase:
 Secretion stimulated by CCK
 (+ Secretin stimulates bicarb-secretion à neutralises chymeàoptimum pH)
 Continues breakdown of starchàeven smaller chunks
• Small Intestine Brush Border:
o Brush-Border Enzymes:
 Membrane-bound
 Act on Oligosaccharides & Disaccharides à Monosaccharides
 Enzymes are multifunctional – ie. 2 Enzymes in 1 (2 different active sites)
Sucrase: Sucrose  Glucose + Fructose
Lactase: Lactose  Glucose + Galactose
Maltase: Maltose  Glucose + Glucose
Isomaltase: Maltriose  Glucose + Galactose

7. Large Intestine:
o Non-Starch-Polysaccharides & Resistant Starches escape enzymatic breakdown
until now.
o Microbial Enzymes:
 Break down NSPs & RSs à short chain fatty acids. (SCFAs) +
CO2/H2/Methane (Flatus)
 SCFAs: Acetate/Propionate/Butyrate
 SCFAs are absorbed into blood

8. Carbohydrate Absorption:
• Mouth
o None
• Stomach
o None
• Small Intestine
Via Secondary Active Transport:
o Apical GLUT 1: Glucose & Galactose GLUT 2: Basal
o Apical GLUT 5: Fructose GLUT 2: Basal
• Large Intestine:
o None
Glucose Dynamics: Blood-Glucose
• Insulin Dependent:
o Fat synthesis/deposition
o Glucose uptake into muscles (glycogenolysis)
o NB: if insulin dependent paths are blocked (diabetes) blood glucose increasesà glucose excreted
through urine.
• Insulin Independent:
o Glucose uptake into liver (glycogenolysis)
o Glucose uptake into brain - fuel.
Glycaemic Index (GI)
- A measure of how rapidly a carbohydrate releases glucose into the blood during digestion.
- High GI – Quick glucose release
- Low GI – Slow glucose release

9. Dietary Fibre:
• NSPs (Non-Starch Polysaccharides)
o Soluble Fibre
 Non-cellulose
 In fresh fruit/vegetables/oats/seeds
 Increases viscosity of intestinal contents
 End up fermented by bacteria in colon
o Insoluble Fibre
 Cellulose (plant walls)
 Provides bulking to colonic contents.
 Keeps people regular
 Most not fermented in colon
• *Starch
o Resistant Starch (RS)
 Escapes digestion in small intestine
 Passes through to large intestine.
 Has similar effects as NSPs
NB: *starch isn’t strictly a ‘dietary fibre’, but RS has similar effects as both soluble &
insoluble fibre

10. DIGESTION OF PROTEINS
 Digestion of proteins to Amino Acid occurs in 3 locations
1. Intestinal lumen
 stomach – pepsin (digests collagen)
 small intestine - endopeptidases
- exopeptidases
2. Brush border – oligopeptidases, dipeptidases
3. Cytoplasm of mucosal cells – dipeptidases
Activation/Destruction of Proteases
 Proteolytic enzymes are activated and destroyed very rapidly
- Enterokinase activates trypsinogen
- Trypsin is autocatalytic
- Trypsin activates other proenzymes
- Proteolytic enzymes digest themselves
Protein Digestion and Absorption
 Luminal digestion produces 40% amino acids and 60% small peptides
- Amino acids
 Secondary active transport (Na+ dependent)
 Facilitated diffusion
- Di- and Tri- peptides
 different carrier system than amino acids
 absorbed faster than amino acids
 hydrolyzed to amino acids in cytoplasm
 Abnormalities of Protein Assimilation
- Pancreatic insufficiency
 Pancreatic or cystic fibrosis
 decreased absorption – nitrogen in stool
- Congenital absence of trypsin
 no trypsin – no other proteolytic enzymes
 protein malabsorption
- Hartnup’s disease
 cannot absorb neutral amino acids
 neutral amino acids can still be absorbed as di- and tri- peptides.

11. Protein Absorption in GI Tract:
• RDI: approx 125g/day
• Sources: meats, eggs, dairy, seeds, nuts, legumes......
• Why eat proteins:
o Proteins consist of amino acids
o Some “essential” amino acids can’t be synthesised by the body àmust be
ingested
o Other “non-essential” amino acids can be synthesised in the body.
• Stomach:
o Chief cells – secrete pepsinogen
o Parietal Cells – secrete HCl
o Pepsinogen + HCl à Pepsin (protease) [more specifically – an endopeptidase]
o Pepsin: breaks peptide bonds in the middle of proteins  smaller polypeptides
NB: pepsin is secreted as a ZYMOGEN. Ie. An inactive form à doesn’t activate until it
reacts with HCl in the stomach lumen. That way it doesn’t digest the cells that secreted it.
A ZYMOGEN requires a biochemical change for it to become an active enzyme.
NB: newborns lack the ability to digest proteins – prevents breakdown of IgA antibodies in the
colostrum
- Protects infant’s GI tract from infection + antibodies endocytosed into bloodsteam – even broader
immunity
Small Intestine:
Proteases break large polypeptides à smaller polypeptides à single amino acids.
o Pancreatic Proteases:
 Trypsinogen à Trypsin (Zymogen [trypsinogen] is activated by brush border enzymes)
 Chymotrypsinogen à Chymotrypsin (activated by Trypsin)
 Procarboxypeptidase à Carboxypeptidase (activated by Trypsin)
o Brush-Border Proteases:
 Aminopeptidase: - cleaves 1 amino acid at a time
 Dipeptidase: - cleaves 1 amino acid at a time

12. Protein Absorption:
• Single Amino Acids + some Di/Tri-Peptides
• Absorbed mainly in Small Intestine:
o By Enterocytes (absorptive cells of SI)
o Via cotransport with Na+ ions.
o Intracellular Peptidases continue breakdown of Di/Tri-Peptides
o Basolateral transporters – A.As & Peptides àEnter capillary blood in villi.

13. Digestion/Absorption of LIPIDS:
• Average Intake:
o 60-100g/day
• Composition:
o 90% Triglycerides (TAGs)
o 10% Cholesterol/Cholesterol Esters/Phospholipids/Fat-Soluble Vitamins A,D,E,K.
• Emulsification:
o Lipids are insoluble in H2O
o Gastric contractions disperse fat ‘pools’ evenly
amongst chyme.
o Fatty ChymeàDuodenum à Pre-treated with Bile-
Salts
o Bile Salts: Amphiphilic molecules – polar & non polar
ends
 Emulsify Large Lipid Droplets à tiny tiny
droplets à High Surface Area
 High S.A. = more access to lipases

14. DIGESTION OF LIPIDS
Assimilation of lipids – Overall scheme
Basic steps of Lipid Assimilation
 Most dietary lipid is neutral fat or triglyceride. Three main processes must
occur for triglyceride to be absorbed into blood.
1. Emulsification – large aggregates of dietary triglyceride are broken down
2. Enzymatic digestion – to yield monoglyceride and fatty acids. Both can
diffuse into enterocyte
3. Reconstitution of triglyceride and chylomicron formation.
Summary of Lipid Digestion Products

15. “Malabsorption”
 Malabsorption – general phenomenon is defined clinically in terms of fat
malabsorption because fat can be measured easily in stool, unlike
carbohydrates and proteins
 Motility disorders – moving through too rapidly
 Digestion disorder – pancreatitis/cystic fibrosis – (not enough lipase)
 Absorption disorder – tropical and non-tropical sprue – resection of small
intestine.
Sprue
 Diseases that result in decreased absorption even when food is well digested
are often classified as “sprue”.
- Non-tropical sprue
 also known as celiac disease
 allergic to gluten (wheat, rye)
 destroys microvilli and sometimes villi
- Tropical sprue
 Bacterium
 treated with antibacterial agents
 Steatorrhea – if stool fat is in the form of FFA – digestion has occurred.
Fluid and Electrolyte Absorption and Secretion
Fluid entering and exiting the Gut
Water movement in Small intestine
 Water moves into or out of gut lumen by diffusion in accordance with osmotic
forces
- Hypotonic chyme – water is absorbed (less solute present)
- Hypertonic chyme – waters enters intestine (more solute present)
 Chyme is isosmotic with plasma except in colon. Stool water is hypertonic.
Sodium Absorption causes Water Absorption
 Sodium is absorbed by epithelial cells (enterocytes) of small intestine
 Sodium uptake creates negative electrical potential in gut lumen, that provides
gradient for chloride uptake.
 Water follows sodium and chloride in accordance with osmotic forces.

16. • Digestion: Lipases
o Gastric Lipase: Stomach – Secreted by Chief Cells
o Pancreatic Lipase: Pancreas – Secreted in Active Form
o H2O soluble enzymes
o Catalyse Hydrolysis of Ester bonds between the Glycerol Backbone & Fatty Acids of
Triglycerides.
o Mostly yields 1 MonoAcylGlyceride + 2 Free Fatty Acids
o Rarely yields 1 Glycerol + 3 Free Fatty Acids

17. Absorption: Micelles
o Monoglycerides + Fatty Acids:
 Retain association with Bile Acids à Aggregate to form Micelles.
 Micelles: aggregates of mixed lipids & bile acids suspended within chyme.
 Micelles in contact with brush-border-membrane of Enterocytes release FAs &
Monoglycerides  diffusesimple into Enterocyte.
 FAs & Monoglycerides à Endoplasmic Reticulum à used to synthesise Triglycerides
 Triglycerides à Golgi Apparatus  Packaged with Cholesterol+Lipoproteins 
Cholymicrons (The lowest-density Lipoprotein)
 Cholymicrons in Vesicles  transported to Basolateral Membrane à Exocytosed into
Interstitium.
 Interstitial cholymicrons  acteal (Lymphatic Vessel in Villus) à Lymphatic System 
Blood
 Blood-Borne Cholymicrons rapidly utilized throughout the body.
o Cholesterol:
 Absorbed in Small Intestine via specific transporter à enterocyte.
 Cholesterol is incorporated into cholymicrons    shuttled into blood by process
above.
 Cholesterol Homeostasis: Balance of Synthesis/Absorption/Excretion(in bile) of
Cholesterol.