Gastrointestinal Physiology

Jun Hee Lee, Ph.D

leeju@[Link]

Dept. Molecular and Integrative Physiology

109 Zina Pitcher Pl., 3019 BSRB
(734) 764-6789

1
 GI Physiology Lectures
• Lecture 1
– GI system overview
– Mouth, Pharynx, Salivary gland and Esophagus
– Stomach

• Lecture 2
– Intestines
– Pancreas
– Liver and Gallbladders

• Lecture 3
– Digestion and absorption of carbohydrates
– Digestion and absorption of proteins
– Digestion and absorption of fat
– Absoprtion of fluid, mineral and vitamins

2
Digestion & Absorption of
Carbohydrates

3
 Carbohydrates Digestion
:Overview
• Average daily intake of carbohydrates is
about 250- 300 g

• Average American diet: 50% calories come

from carbohydrates and sugars

4
 Carbohydrates
The carbohydrates are divided into 3 chemical groupings:

Carbohydrates must be digested to monosaccharides before

they get absorbed

5
 Monosaccharides

Hexose
- a monosaccharide with six carbon atoms, having the chemical formula
C6H12O6 = (C-H2O)6
- The most significant nutrients found in foods.

6
Disaccharides

Table Sugar

Milk

Hydrolysis
of polysaccharides

7
 Polysaccharides (1)

Starch & Glycogen – Energy Storage Fibers – Structural Support

8
Polysaccharides (2)

9
Polysaccharides (3)

10
Polysaccharides (4)

11
Digestion and absorption of carbohydrates

Polysaccharides
Starch
Glycogen
Disaccharides
Maltose (2 glucose)
Sucrose (fructose and glucose)
Lactose (galactose and glucose)
Monosaccharides
Fructose
Glucose Absorbed
Galactose
Indigestible carbohydrates (fiber)
Cellulose

12
 Digestion of carbohydrates

Absorbed

13
Motility Oral Cavity and
Esophagus
Secretion M Swallowing and chewing
S Saliva and lipase
Digestion
D Carbohydrates and fats (minimal)
Absorption A None

Small Intestine
M Peristalsis
S Mucus, CCK, secretin, GIP, and
other hormones
D Carbohydrates, fats, polypeptides
and nucleic acids
A Peptides, amino acids, glucose,
fructose, fats, water, mineral,
vitamins

14
 Intestinal digestion of
Carbohydrates (1)

Luminal Membrane

Disaccharides
Starch Trisaccharides Monosaccharides
-limit dextrin
Amylase Maltase
Isomaltase
Sucrase
Lactase
Pancreatic Brush Border
Enzymes Enzymes

15
 Intestinal digestion of
Carbohydrates (2)

Amylase Amylase

Amylase

16
 Intestinal digestion of
Carbohydrates (2)
maltose Maltase glucose
maltotriose Glucoamylase
-limit dextrin Isomaltase glucose
isomaltose
Sucrase glucose + fructose
sucrose
Lactase glucose + galactose
lactose

Brush border enzymes bound to membrane

17
 Absorption of carbohydrates
- Na+-Dependent co-transport:
SGLT1 (sodium-glucose transporter 1)
Absorption of sugar is dependent on low
intracellular Na+ maintained by the Na+/K+-ATPase.
(From intestinal lumen to enterocytes)

- Facilitated diffusion:
GLUT 5 (glucose transporter 5)
Apical transport of fructose. (From intestinal lumen to
enterocytes)
GLUT 2 (glucose transporter 2)
Basolateral transport of monosaccharides
(From enterocytes into blood)

18
Absorption of monosaccharides

Basolateral Apical

ATP is
required!
K+ Na+
Na+ SGLT 1
Glucose/Galactose
Glucose
Galactose
GLUT 2 Fructose
K+ Fructose
GLUT 5
Facilitated
Diffusion
Enterocyte

19
 Digestion & Absorption of
Carbohydrates at Brush Border

Maltase = alpha-glucosidase = a subunit of Glucoamylase

Alpha-dextrinase = Isomaltase

20
 Lactose Intolerance
Lactase glucose ++ galactose
galactose
Lactose glucose

Increased luminal osmolality

Net water accumulation in lumen Fermentation

Luminal distension by gut bacteria

Enhanced peristalsis

Watery diarrhea Gas

21
Digestion & Absorption of
Proteins

22
 Digestion and absorption of
proteins: Overview
- Required ~ 0.75g/kg b.w. of dietary protein
- ~70-90 g dietary protein per day in American diet
- Proteins must be digested into amino acids or small
peptides before they are absorbed
- Proteins secreted into lumen also get digested and
absorbed
- Nine essential amino acids are not synthesized and must
be obtained from diet
- Both, amino acids and di- and tri-peptides are absorbed
- Digestion includes a luminal and brush border phase

23
 Overview
Proteins are broken down into:
- Polypeptides
Long chains of amino acids
- Peptides
Short chains of amino acids (2-3 a.a.)
- Amino Acids
Basic unit of proteins

Absorbed into enterocytes

24
 Amino Acids
Carboxyl
Group
Amino
Group

Side
Chain

25
Peptides & Proteins

26
 Protein digestion
- There are many different proteases for protein
digestion

- The number of enzymes required for digestion of

proteins is greater than the number for digestion of
carbohydrates
There are a greater number of amino acids than simple
sugars

The greater array of peptide bonds requires more

enzymes to break all of the bonds

27
Motility
Secretion
Digestion
Absorption

Stomach
M Peristalsis
S HCl, pepsinogen, bicarbonate,
mucus, gastric lipase, gastrin, and
histamine
D Protein and fats
A Lipid soluble substances (alcohol
and aspirin)

Small Intestine
M Peristalsis
S Mucus, CCK, secretin, GIP, and
other hormones
D Carbohydrates, fats, polypeptides
and nucleic acids
A Peptides, amino acids, glucose,
fructose, fats, water, mineral,
vitamins

28
Protein digestion in Stomach

- Chief cells secrete pepsinogen

• Pepsinogen is the inactive form

(zymogen)
• HCl cleaves pepsinogen to pepsin
• Pepsin = active form

- Parietal cells secrete HCl

29
 Protein Digestion in
Small Intestine (1)
- Pancreatic proteases
• Trypsin
• Chymotrypsin
• Carboxypeptidase

- Brush border proteases

• Enterokinase
• Aminopeptidases
(at least 20 different peptidases)

- Luminal enterokinase converts trypsinogen to trypsin

- Trypsin activates other zymogens

30
 Protein Digestion in
Small Intestine (2)
Peptides are digested in the small intestine in 3 locations

Luminal Membrane

brush
luminal Peptides (60%) border Amino Acids
Peptides Amino Acids (40%) Small peptides (2-3 aa)
(stomach
digestion)

Intracellular
intracellular
peptidases

Amino Acids

31
 Absorption of Proteins:
Overview
- There are at least 7 different amino acid
transporters

- Some amino acid transporters are Na+ dependent

(similar to glucose transporter SGLT1).

- Small peptides are absorbed by a H+ linked co-

transporter and broken down by intracellular
peptidase.

32
Absorption of Amino Acids

amino
acid
ATP is
required!
Na+

Enterocyte

33
Absorption of Small Peptides

Small
peptidases small peptides
amino
acids peptides

H+

H+

ATP is Na+
required!

Enterocyte

34
 Summary of Protein
Digestion and Absorption

Blood
capillary
network

From the interstitial fluid,

amino acids diffuse
into the blood via capillary
pores.

35
Absorption of Intact Proteins

Transcytosis
endocytosis/exocytosis

e.g. In infants, maternal antibodies from

milk can be transported this way

Fujita et al., 2007 Med Mol Morphol.

36
Digestion & Absorption of
Fat

37
 Fat Digestion Overview
- Digestion of fat is difficult because it is not
water soluble
- Enzymes that break down fat must work in
an aqueous environment
- Fat must be emulsified before digestion
- Bile is the major emulsifier that is essential for
fat digestion

38
 Bile Components
(500 ml/day)
• Bile Salts
• Phospholipids (lecithin) Emulsifiers
• Cholesterol (4%)
• Ions (HCO3-) Neutralize Acid
• Metabolic end products
Not Important
• Bile pigments (bilirubin) for Digestion

39
Bile Salts

- Synthesized in liver from

cholesterol

- Amphipathic molecule

- Emulsify fat

40
Bile Components

41
 Digestion and absorption of fats

Bile salts and

phospholipids convert
large fat globules into
smaller pieces with
polar surfaces that
inhibit reaggregation.

42
 Digestion and absorption of fats

Pancreatic Lipase
colipase

Emulsified fat globules are small

enough that lipase enzymes gain
access to degrade triglycerides
to monoglycerides and fatty acids,
which enter the absorptive cells
By simple diffusion or aggregate
to form loosely held micelles,
which readily break down.

43
 Digestion and absorption of fats

Big Droplets of Fat

Small Droplets of Fat

Micelles

Fatty Acids and

Monoglycerides

Chylomicron Assembly

Distribution and Processing

44
 Steps on fat digestion and
absorption

1. Emulsification
Homogenous mixture of fat and bile in duodenum

2. Digestion
Triglycerides Monoglycerides + Free Fatty acids
pancreatic
lipase
Phospholipids Lysophospholipid + Free Fatty acids
phospholipase

Minor (~30%) of fat digestion can be conferred by lingual and gastric lipase
(acidic lipase that does not require bile/colipase)

45
 Steps on fat digestion and
absorption (cont.)
3. Diffusion
Products of digestion are not very soluble and form
micelles that diffuse to the enterocyte surface

4. Absorption
Occurs by free diffusion across the membrane and by
specific transport mechanisms

5. Transit into the Body

Triglycerides get reassembled inside enterocytes
and are packaged into lipoprotein structures to
enter body

46
 Transit into the Body

- Once inside the enterocyte fat components are

reassembled into triglycerides

- Lipoprotein complex termed chylomicron

- Chylomicrons exit out the basolateral membrane into

the lacteal

- Small chain fatty acids (<12 carbons) are more

soluble in water and can pass into the blood

47
48
49
50
Fatty Acid
Transporters

51
Fatty Acid
Transporters

52
 Ways to Alter Fat Absorption

1. Olestra – Fake fat; can’t be digested by lipase

2. Orlistat (Xenical) – Covalent Lipase inhibitor

Side effect of both is fat malabsorption, and diarrhea, if on

diet with significant high fat content.
Absorption of
Vitamins

54
 Absorption of Vitamins

1. Water soluble vitamins

Na+ coupled cotransport
Vit B, Vit C, Biotin

2. Fat soluble vitamins

Similar to lipids.
Fat malabsorption can lead to vitamin deficiency.
Vit A, Vit D, Vit E, Vit K

3. Vitamin B12
Large charged molecule
Binds to Intrinsic Factor
Receptor mediated endocytosis in Ileum

55
 Absorption of Vitamin B12 (1)
- Vitamin B12 (cobalamin - Cbl) is the
exception
• Vit B12 is a very large charged molecule

• Absorbed only when bound to Intrinsic Factor

• Intrinsic factor is secreted by acid-secreting

parietal cells in stomach

• Vit B12-IF complex binds to receptors

on luminal surface of ileal absorptive cells
(lower ileum)

• Internalized by endocytosis
 Absorption of Vitamin B12 (2)
R protein: A protein secreted
in saliva that binds to vitamin
B12 and prevents its
degradation in the stomach.

Intrinsic Factor (IF):a

glycoprotein produced by the
parietal cells of the stomach. It
is necessary for the absorption
of vitamin B12 (cobalamin) later
on in the small intestine (lower
illeum).

57
 Absorption of Vitamin B12 (3)
Vitamin B12 is required for erythrocyte formation
- deficiency results in pernicious anemia

Besides diet, what defects

could lead to Vit B12 deficiency?
Loss of parietal cells
- gastritis
- elderly - atrophic gastritis
Injury to the ileum/surgical removal

How to treat?
- Injection
- Overconsumption (Liver therapy)
(Nobel Prize in Physiology or Medicine 1934 to Whipple, Minot & Murphy)

Yoon Eun-hye (Korean: 윤은혜; born October 3, 1984) – pernicious anemia

 Summary of major absorptions
in the small intestine

Duodenum fats, sugars, amino acids

Jejunum some sugars and amino acids
Ileum bile salts, vitamin B12

59
Absorption of
Fluids

60
 Fluid absorption:
Overview
- Majority of water is absorbed in the small intestine.
- Absorption occurs by osmosis.
Transcellular uptake (through cells)
Paracellular uptake (between cells)

- If digestion is inhibited absorption does not occur and

fluid remains in the lumen

-Inability to fully digest

a meal results in diarrhea.

61
 Fluid absorption

SGLT1

62
 Cholera Toxin & Diarrhea
Cholera toxin increases lumen
cAMP levels to activate
Cl- channel in crypt cells
of small intestine
(jejunum)

Na+ and H2O follow by

osmosis

> 10L H2O secreted/day

basolateral
Nature Reviews Drug Discovery (2009) 8:153

63
 Fluid absorption
- Diarrhea is a serious problem for young children,
especially in underdeveloped countries.
- Biggest danger is due to dehydration.
- A simple and effective treatment has been
developed based on knowledge of absorption
of fluid in the gut.
- Oral Rehydration Therapy (ORT) uses a solution
with a 1:1 mixture of glucose and NaCl. SGLT1
absorbs the solutes and water follows by osmosis.

Since its introduction and development for widespread use in the latter part of the
20th century, oral rehydration therapy has decreased human deaths from
dehydration in vomiting and diarrheal illnesses, especially in
cholera epidemics occurring in children. It represents a major advance in global public
health.

Prior to the introduction of ORT, death from diarrhea was the leading cause of infant
mortality in developing nations. Between 1980 and 2006, the introduction of ORT is
estimated to have decreased the number of infant deaths, worldwide, from 5 to 3
million per year.

64
 Fluid absorption

SGLT1

65
Between 1980 and 2000, ORT decreased the number of children under five dying of diarrhea
from 4.6 million worldwide to 1.8 million—a 60% reduction.

66
 Summary Points
CARBOHYDRATES
• Carbohydrates, their characteristics and digestibility.
- mono-, di-, poly-saccharides (starch, glycogen, cellulose)
• Enzymes that digest carbohydrates
• Carbohydrate Absorption
- SGLT1, GLUT2 and GLUT5

PROTEINS
• Enzymes that digest proteins
• Sites of digestion
• Absorption of amino acid and peptides

FATS, VITAMINS & FLUIDS

• Bile – how it is involved in fat digestion
• Absorption of Vitamin B12
• Fluid absorption and Oral Rehydration Therapy (ORT)

67
Summary: overview

Oral cavity
•Chewing, swallowing
•Saliva
Stomach
•Acid secretion
•Production of chyme
•Mixing of food for chemical
digestion in the small intestine
Small Intestine
•Digestion and absorption of
carbohydrates, proteins and fats
•Bicarbonate, bile, pancreatic
enzymes
Large Intestine
•Absorption of water, ions and
Minerals. Exit of material from the body

68
Summary: Overview GI Regulation

Gastrin (stomach) induces acid

secretion and motility of digested
food in the intestine

Acid and digested food

(fats and amino acids)
induce secretin and CCK (intestine)

Secretin and CCK induce pancreatic

enzyme and bile mobilization into the
intestine.

69
THANK YOU!

70