Introduction

• Primary function: move nutrients, water and

electrolytes from the external environment
into the body’s internal environment
• Central to regulation and integration of
metabolic processes throughout the body
• Proper functioning necessary for whole-body
homeostasis
• 10% of health care costs related to GI system
 Anatomy of the digestive system
-Extends from mouth èlarge
intestine (~15 ft length in live person)
-GI tract: a long tube with muscular
walls lined by transporting and
secretory epithelial

-Stomach èanus=GUT

-Digestion: mechanical and chemical

breakdown of food primarily occurs in
the gut

-joined by secretions from accessory

glandular organs Vander’s Human Physiology, 13th ed. Pg. 534
-salivary glands, liver, gallbladder, Technically GI tract is continuation
pancreas of external environment (bacteria)
 Anatomy of the digestive system
Digestion begins in the mouth with mastication and the
addition of saliva
-Three pairs of salivary glands with multiple functions:

1. Moisten and lubricate

food

2. Amylase partially
digests polysaccharides

3. Dissolve some food

molecules (taste)

4. Lysozyme kills bacteria

 Anatomy of the digestive system
Esophagus
Passageway from mouth to stomach
-upper and lower esophageal sphincters
-wall: top 1/3 is skeletal muscle, bottom 2/3
smooth muscle
-moves food via peristaltic waves

1.

2.
3. Digestion continues in stomach,
mixing food with acid and enzymes
to create chyme
Valve (sphincter)
 Small intestine
Majority of digestion
takes place here

1.
First 25cm

2.
260cm

3.

-liver and pancreas release

exocrine secretions into the
duodenum
Principles of Anatomy and Physiology, 14th ed. Tortora. Pg 914
 Large intestine (colon)
-larger diameter but shorter ~150cm
2.

1. 3.

4.

Principles of Anatomy and Physiology, 14th ed. Tortora. Pg 925

-1.5 L of watery chyme pass into Feces entering the terminal
here each day section of the large intestine
-water and electrolytes removed (rectum) trigger a defecation
to create semisolid feces reflex
 GI Layers
Basic structure of GI wall is similar in both the stomach and
intestines with slight variations from one section to another

ENS

Enteric nervous system

Vander’s Human Physiology, 13th ed. Pg. 536
 GI Layers

Principles of Human Physiology, 5th ed. Stanfield. Pg 569

 Mucosa

1.

2.
3.

Gastric folds increase surface area: Rugae

 Mucosa
Plicae further increase surface
area

Gastric glands
 Mucosa
Epithelium (most variable)
– Include transporting
epithelial cells
(enterocytes in sm.
Intestine), endocrine and
exocrine secretory cells
– Junctions very tight in
stomach and colon, leaky
in small intestine
– Short lifespan (a few
days) GI stem cells
constantly producing
new cells. ~17 billion
replaced daily
 Mucosa
• Lamina propria
– Subepithelial tissue
containing nerve
fibres, small blood
vessels and lymph
vessels
• Muscularis mucosae
– Thin layer of smooth
muscle that can alter
the surface area
available for
absorption
 Submucosa

Submucosal plexus

Middle distensible layer containing larger vessels (lymph

and blood) and the submucosal plexus; one of the major
nerve networks in the enteric nervous system
 Muscularis externa and Serosa

Muscularis externa: 2 or 3 layers of smooth muscle: circular decrease

diameter, longitudinal shortens the tube. Contains myenteric plexus
Serosa: outer covering of connective tissue that is a continuation of the
peritoneal membrane, sheets of mesentery hold intestines in place.
 Digestive function and processes

Secretion can also mean movement

of water and ions from ECF to lumen
 Challenges of the digestive system
Mass balance
Avoiding autodigestion:
breaking food down into small
enough molecules to be
absorbed without digesting
the cells of the GI tract

Defense: absorbing water and

nutrients while preventing bacteria,
viruses and other pathogens from
entering the body.
-mechanisms include mucus,
digestive enzymes, acid and the We secrete a lot more than
largest collection of lymphoid tissue we actually ingest
-80% of lymphocytes in small intestine
 Fluid Secretions
• Water
– Ions are transported from ECF into the lumen
• Creates osmotic gradient for water movement
• Digestive enzymes
– Exocrine glands (salivary and pancreas)
– Epithelial cells in stomach and small intestine
• Proteins synthesized on rough ER and packaged in secretory vesicles
until needed
• Once released some remain bound to apical membrane by lipid
anchors
• Some are released in an inactive form: zymogen (stock pile without
cellular damage)
• Mucus
– Viscous glycoprotein (mucins) secretions that protect GI cells
and lubricate the contents
• Mucus cells in stomach and salivary glands, goblet cells in intestine
 Fluid secretions
Most fluids facilitate digestion

Enzymes
preferring acidic
conditions

Enzymes preferring
alkaline conditions
 Motility

Skeletal
Two purposes: muscle
1. Moves food from
mouth to anus
2. Mechanically
mixing food breaks Smooth
it into uniformly muscle
small particles
 Motility

GI motility determined by properties

of smooth muscle and modified by
chemical input from nerves,
hormones and paracrine signals
 Motility

Sphincters

Posterior region of Slow waves modified by

stomach, small, large chemical input from neurons,
intestines hormones and paracrine signals
 Motility
Slow waves likely originate in a network of cells known
as the interstitial cells of cajal (ICC)

-modified smooth muscle cells

serving as the pacemaker for slow
wave activity
Slow waves begin
spontaneously in
ICC and spread to
adjacent smooth
muscle through gap
junctions

-different regions
controlled by https://liferaftgroup.org/2012/04/cellular-origin-of-gist-from-the-good-cells-perspective/

different ICC groups 3-12 waves/min

 Motility
Three basic patterns of contraction occur in the GI system bringing
about different types of movement
1. Migrating motor complex (motilin)

-between meals
-usually begins in the stomach and passes
from section to section, terminating at the
ileum

~90-120 minutes (first 45-60 minutes

quiescent)
-20-30 min period of infrequent peristaltic
contractions
-5-15 minute cycle rapid forceful contractions

-sweeps food remnants and bacteria out of

the upper GI tract and into the large intestine
 Motility
Three basic patterns of contraction occur in the GI system bringing
about different types of movement
-during or following a meal
2. 3.

Progressive wave of contraction Small segments alternatively

of circular muscle behind a contact and relax circular and
mass (bolus) of food (2-25cm/s) longitudinal (churns and mixes)
Peristalsis

Segmental
 Regulation of GI function
Motility and secretion are the primary regulated functions
in the GI system.
Neural
-submucosal and myenteric plexuses form the
ENS: 100-500 million neurons
-neurons synapse with each other, smooth
muscles, glands and epithelial cells
-short reflexes integrated entirely within the ENS
-long reflexes integrated within the CNS

GI Peptides
-hormones, neuropeptides and cytokines
The ENS shares similarities with the CNS
• Intrinsic neurons: entirely within the ENS
• Neurotransmitters and neuromodulators: ~30
neurotransmitters many identical to CNS
(serotonin, ACh, VIP, NO)
• Glial support cells: similar to astrocytes
• Diffusion barrier: like BBB
• Integrating center: can function autonomously
 ENS reflexes

Myenteric plexus: motility

Submucosal plexus: secretion from GI
secretory cells
 If a long reflex begins in the
brain it is a cephalic reflex
(feedforward and emotional)

Sensory info
also sent to CNS
ENS receives information from the CNS via
autonomic neurons
Parasympathetic input enhances GI function, sympathetic inhibits
 GI Peptides
(Hormones, neuropeptides and cytokines)

• Can act as hormones or paracrine signals

• Excite or inhibit motility and secretion
• Can be secreted in to lumen to act on apical
membrane receptors or ECF to act on
neighbouring cells
• Some act outside the GI tract (brain)
eg. Cholecystokinin-satiety, ghrelin-hunger
• More than 30 peptides have been identified
from the GI mucosa, only a handful are
considered hormones
Glucose-dependent insulinotropic peptide

Vasoactive Small intestine Smooth muscle relaxation

ENS neurons Increase secretions from small
intestinal pancreas
peptide (VIP) intestine and pancreas
 Hormone families
• Gastrin family
– Gastrin
– cholecystokinin
• Secretin family
– Secretin
– Vasoactive intestinal peptide
– Gastric inhibitory peptide (glucose-dependent
insulinotropic peptide)
• “Other”
– motilin
 Integrated function
• Integrated function within the digestive system is
often described in three phases:
1. Cephalic/oral phase: digestive processes
occurring before food enters the stomach.
2. Gastric phase: digestive processes in the
stomach.
3. Intestinal phase: digestive processes in the
intestines.
– Small intestine
– Large intestine
 Cephalic phase
Digestive processes can actually begin before food enters
the mouth and are reinforced once food enters the GI tract

Long reflexes beginning in

the brain known as the
cephalic phase of digestion

Increased parasympathetic
output from medulla to
salivary glands (via facial
and glossopharyngeal) and
to the enteric nervous
system (via vagus nerve:
vagal reflex)
Chemical and mechanical digestion begin in the mouth
Mechanical digestion begins with
mastication (chewing) of food by teeth

-tongue and lips also helps manipulate

food

https://media.giphy.com/media/3ZtiHp055ExeE/giphy.gif -joined by a flood of saliva from the

three pairs of salivary glands (parotid,
Four functions: submandibular and sublingual)

1. Soften and moisten food

2. Digestion of carbohydrates
(amylase)
3. Dissolve foods (taste)
4. Defense (lysozyme)
 Saliva is an exocrine secretion
1.5 L/day: 99.5% water, 0.5% solutes
-Na+, Cl-, K+, HCO3-, PO4-
-amylase, lysozyme, mucus, immunoglobulin A

Secretory cells found in clusters known as acini

-Glands are not identical

Parotid: watery solution with
amylase
Submandibular: similar to
parotid plus some mucus
Sublingual: mainly mucus

Primarily under parasympathetic control

 Swallowing moves food from mouth to stomach
Deglutition is a reflex that pushes a bolus of food or liquid
into the esophagus
Pressure against soft palate
and back of mouth (voluntary)
activate sensory neurons going
to the medulla

-medulla (swallowing center):

somatic motor outputs to
pharynx and upper esophagus
and autonomic outputs to the
lower esophagus
-Soft palate closes off nasopharynx
-contraction moves larynx up and forward, glottis closes trachea
-upper esophageal sphincter relaxes and opens
 Swallowing moves food from mouth to stomach
Deglutition is a reflex that pushes a bolus of food or liquid into the
esophagus

Epiglottis covers airways

Lower esophageal sphincter

tension relaxes
 Gastroesophageal reflux disease (heartburn)
LES technically not a true anatomical sphincter

https://www.mayoclinic.org/diseases-conditions/gerd/symptoms-causes/syc-20361940

-churning action of stomach contraction can cause backflow

-Negative intrapleural pressure during inspiration can cause esophagus
to expand drawing gastric acid and pepsin from the stomach
Integrated function: Gastric phase
3.5 liters of food, drink and saliva
enter the stomach each day

Stomach has three general functions:

1. Storage: stores food and regulates

its passage into the small intestine

2. Digestion: chemical and

mechanical digestion into chyme

3. Defense: Destroys bacteria and

other pathogens in food and
pathogens trapped in airway
mucus (mucociliary escalator)
Motility and secretion initiated during cephalic phase now reinforced
 Storage and motility
Upon swallowing food, parasympathetic
neurons to the ENS cause the fundus of
the stomach to relax: receptive
relaxation.

-distension of stomach enhances motility

-weak peristaltic waves (15-25 seconds)

that increase in force proceeding down to
the antrum moves chyme toward pylorus
(propulsion) and then larger particles are
moved back to the body (retropulsion)

-mixes food with acid and digestive

enzymes, small amounts of chyme
squeeze through pylorus
Vander’s Human Physiology, 13th ed. Pg.554
 Gastric secretions protect and digest
G-cells release gastrin
(hormone) in response to
amino acids, peptides and
distension (short reflex-GRP)
-parasympathetic neurons→
ENS: stimulate gastrin
production during cephalic
phase (long reflex)
-stimulates gastric acid
secretion directly from parietal
cells

Indirectly: Stimulates histamine release from enterochromaffin-

like cells (ECL), which then stimulates parietal cells
Acid secretion
Parietal cells
1-3L of gastric acid (HCl)
produced daily with a pH as
low as 1

Stimulated by gastrin from G-cells,

histamine from enterochromaffin-
like cells (ECL) or ACh from from
ENS neurons via long and short
reflexes
 Gastric acid functions
• Stimulates release of pepsinogen from chief
cells, cleaves pepsinogen to pepsin (digests
proteins)
• Denatures proteins making it easier for pepsin
to function
• Kills bacteria and other ingested microorganisms
• Inactivates amylase from saliva
• Stimulates D cells to release somatostatin
 Acid secretion
Free H+ actively transported
across apical membrane

Water dissociates to H+ and

OH- freeing up more H+ to be
actively transported

OH- combines with CO2 via CA

to generate HC03-

HCO3- exchanged for Cl- at

basolateral membrane

Cl- diffuses across apical

membrane through open
channels following
electrochemical gradient
 Acid secretion

Secondary
ICF

LUMEN

Parietal cell Vander’s Human Physiology, 13th ed. Pg.551

 Stimuli for acid secretion
Apical H+/K+ ATPase, Cl- and K+ -stimuli cause exocytosis and
transporters stored in vesicles insertion of apical transporters

Apical

Medical Physiology, 3rd ed. Boron and Boulpaep. Pg.898

Excessive acid treated with H2 receptor

antagonists or proton pump inhibitors Vander’s Human Physiology, 13th ed. Pg.552
 Gastric acid secretion
1. Long reflex
Intestinal hormones
can also inhibit
acid secretion

G cells

ECL-cells
D cells

2. Short reflex Vander’s Human Physiology, 13th ed. Pg.552

 Gastric acid secretion

Intestinal hormones
can also inhibit
acid secretion

Medical Physiology, 2nd update ed. Boron and Boulpaep. Pg.902

 Gastric digestive enzyme secretion
1. Gastric lipase
+
2.

Stimulated by acid
secretion via short
reflex

Vander’s Human Physiology, 13th ed. Pg.553

Paracrine secretion ECL-Histamine
-activates H2 receptors
on parietal cells to
Gastric lipase
+ stimulate HCl secretion

Parietal cell-intrinsic
factor
-forms a complex with
Vit B12 so it can be
absorbed
ECL
D cell-somatostatin
D cell -negative feedback for
acid secretion (G cells,
parietal cells and ECL
cells)
-inhibits pepsinogen
release
Vander’s Human Physiology, 13th ed. Pg.553
Mucus secretion
Mucus and HCO3- secreted from mucous
cells
-mucus secretion stimulated by
parasympathetic input and irritation
-HCO3- by parasympathetic input and H+

(50-200um)
 Peptic ulcer
-a sore or break in the lining of the stomach or duodenum

Excessive acid
production
-gastrin
secreting tumors

Nonsteroidal anti-
inflammatory drugs
(NSAIDS)

Helicobacter pylori
https://www.mayoclinic.org/diseases-conditions/peptic-ulcer/symptoms-causes/syc-20354223
 H. Pylori
For decades stress, spicy foods and over production of acid
was believed to cause peptic ulcers

Barry Marshall and Robin Warren hypothesized bacteria

caused the majority of peptic ulcers (1982)

Nobel prize in Physiology and Medicine in 2005

 https://upload.wikimedia.org/wikipedia/commons/1/1c/H._pylori_urease_enzyme_diagram.svg

https://en.wikipedia.org/wiki/Helicobacter_pylori#/media/File:Ulcer-causing_Bacterium_(H.Pylori)_Crossing_Mucus_Layer_of_Stomach.jpg