UNIT 9: DIGESTION

BIOL2420 D01 Lecture Notes

 A) Overview
Ø The digestive system plays a critical role
in breaking down and absorbing the
nutrients, electrolytes, and water the body
needs in order to maintain homeostasis.
Ø In this unit we will examine:
1. Digestive system structure
2. The basic functions of the digestive
system.
3. The regulation of digestive processes.
4. The phases of digestion.
5. Digestion and absorption of
carbohydrates, lipids and proteins.
6. The absorption of water.
7. The elimination of wastes (defecation). Figure 21.6
 B) Basic Functions of the Digestive Tract
1. Motility – food is ingested and moved through Figure 21.2
the tube of the GI tract using the following
processes:
a. Ingestion – taking food into the mouth
b. Deglutition – swallowing of food.
c. Peristalsis – rhythmic wavelike contractions of
smooth muscle that move food through GI tract
(like squeezing toothpaste out of a tube starting
from the closed end and squeezing toward the Figure 21.4
open end).
d. Mass movements – a strong wave of smooth
muscle contraction over a long segment of the
tract (usually intestines). Usually involved in
defecation reflex.
 B) Basic Functions of the Digestive Tract
2. Digestion
a. Mechanical – the physical breakdown of large pieces of food into smaller
pieces. Involves:
i. Mastication – chewing of food and mixing it with secretions from the salivary
glands.
ii. Churning – mixing of food in stomach due to contraction of 3 layers of
smooth muscle.
iii. Segmentation – alternating contractions of smooth muscle between adjacent
areas of the stomach / intestines – mixes material being digested/absorbed.
b. Chemical – the chemical breakdown of large nutrient molecules
(macromolecules/macronutrients) in small molecules (micronutrients)
that are capable of being absorbed. Involves:
i. Acidic pH – important for the chemical digestion of proteins and fats.
ii. Digestive enzymes - act on macromolecules to break them down into
From Marieb and Hoehn 2018.
smaller ones. For example, pancreatic amylase digests complex
carbohydrates like starch and glycogen into disaccharides and
oligosaccharides in the small intestine.
 B) Basic Functions of the Digestive Tract
3. Secretion – various substances are secreted either by
cells lining the tract or cells of accessory organs. Figure 21.2
a. Exocrine secretions – into lumen of GI tract. Includes:
i. Water (note: water is also reabsorbed)
ii. Hydrochloric acid (HCl)
iii. Bicarbonate (HCO3-)
iv. Enzymes
v. Bile
vi. Mucus
b. Endocrine secretions – into blood. Includes hormones such as
gastrin, cholecystokinin, secretin, etc. that help to regulate digestion.
4. Absorption – transport of digested molecules from the lumen of
(primarily) the small intestine into enterocytes (cells of the
intestinal epithelium) followed by transport into the interstitial
fluid and then into the blood or lymph.
 B) Basic Functions of the Digestive Tract
5. Storage and Elimination of Wastes
Ingestion
Ø The large intestine (colon) stores waste and any undigested Food
Mechanical
material until they can be eliminated. breakdown Pharynx
• Chewing (mouth) Esophagus
Ø Excretion of waste by the digestive tract = Defecation • Churning (stomach) Propulsion
• Segmentation • Swallowing
(small intestine)
6. Immune Functions (deglutition)
• Peristalsis
Digestion (esophagus,
Ø Acts as a physical barrier to foreign pathogens. Tight junctions stomach,
small intestine,
between columnar cells of the gastrointestinal epithelium stop large intestine)
Stomach
pathogens and their toxins from entering into the body. Absorption
ØGut microbiome outcompetes harmful microbes and promotes Lymph
vessel
production of antimicrobial peptides on the surface of intestinal
cells (recall Unit 4: the Immune System). Small
intestine
Blood
ØM cells (microfold cells) in small intestine sample gut contents and Large
intestine vessel
Mainly H2O
endocytose any antigens. Antigens are transported to Peyer’s Feces
patches (lymphoid tissue in contact with basolateral membrane of
Anus
M cells) and are presented to dendritic cells, macrophages and B Defecation

and T lymphocytes that will initiate the immune response. From Marieb and Hoehn 2018.
 C) Structure of GI Tract
Ø The gastrointestinal tract is essentially a long tube,
divided into various regions that are specialized to carry
out the basic functions related to digestion. Accessory
organs including the salivary glands, pancreas, liver, and
gall bladder, produce and/or release secretions into the
tube (or blood) that assist the processes of digestion
and absorption.

Schematic representation of the digestive tract.

Modified from Alan F. Hoffman in Barrett, K.E. 2014. Gastrointestinal
Physiology, 2nd Edition. McGraw-Hill Education, Toronto.
 C) Structure of GI Tract
Ø GI Tract structures, listed in order, include:
1. Mouth/Oral Cavity
2. Pharynx
3. Esophagus
Ø Upper Esophageal Sphincter – skeletal muscle – opens so
that food bolus can enter esophagus; closes to prevent
backflow from esophagus into pharynx.
Ø Lower Esophageal Sphincter – closes to prevent backflow
(reflux) of food and gastric juices into the esophagus (i.e.
heartburn).
4. Stomach (passage time ~2.5-5 hours)
Ø Connected to duodenum via pyloric sphincter/valve. This
valve controls the release of chyme (mix of partially
digested food material and gastric juices) into the
duodenum.
Marieb and Hoehn 2018
Similar to Figure 21.1
 C) Structure of GI Tract
Ø GI Tract structures, listed in order, include:
5. Small Intestine – digestion and absorption of nutrients. (passage
time ~2.5-6 hours)
a. Duodenum – main site of chemical digestion
b. Jejunum
c. Ileum
Ø Ileocecal valve – controls release of chyme from ileum into caecum.
Prevents entry of bacteria from colon into small intestine
6. Caecum – blind pouch that includes appendix, leads into
ascending colon. Contains bacteria (probiotics).
7. Large intestine (colon) – absorbs water, vitamins (passage time
~30-40 hours).
Ø Parts: Ascending, Transverse, Descending, Sigmoid colon.
Figure 21.6
8. Rectum
9. Anus – two sphincters involved in the defecation reflex.
Ø Internal Anal Sphincter – smooth muscle, involuntary control.
Ø External Anal Sphincter – skeletal muscle, voluntary control.
 C) Structure of GI Tract
Ø Accessory structures to the GI tract include:
1. Teeth – chop and tear food into smaller pieces.
2. Tongue – manipulates food and plays a role in
taste and swallowing.
3. Salivary glands – secrete saliva which helps to
moisten food and contains digestive enzymes
to begin chemical digestion.
a. Parotid (just anterior to the ears)
b. Sublingual (under the tongue)
c. Submandibular (under the lower jaw bone)
4. Liver – produces bile and filters and detoxifies
absorbed nutrients.
5. Gall Bladder – stores, concentrates and releases
bile, which acts to emulsify fats and increase the
surface area for the action of pancreatic lipase.
6. Pancreas – secretes digestive enzymes and
alkaline fluid into duodenum.
Figure 21.1
 C) Structure of GI Tract Figure 21.1
Ø Tissue Layers of the GI tract wall:
1. Mucosa
Ø Includes:
a. Mucosal Epithelium – lines inside surface of the tract
Ø Apical surface is in contact with lumen of tract, basolateral surface in
contact with basement membrane.
Ø Esophagus and rectum – have stratified squamous epithelium
(provides protection from abrasiveness of swallowed foods and solid
wastes respectively).
Ø Stomach and Intestines – have simple columnar epithelium (involved
in absorption and secretion)
b. Lamina propria – holds the epithelium in place
Ø Loose connective tissue layer
Ø Contains small blood vessels, lymph lacteals (i.e. lymphatic capillaries,
which will play an important role in fat absorption).
c. Muscularis mucosae
Ø Thin layer of smooth muscle separating mucosa and submucosa.
Contraction can help to dislodge food from the folds/crypts of the
intestine.
 C) Structure of GI Tract
Ø Tissue Layers of the GI tract wall:
2. Submucosa
Ø Thick layer of connective tissue containing glands, nerves and blood vessels.
Ø Contains the submucosal plexus, the first nerve network of the enteric
nervous system.
3. Muscularis externa
Ø Two layers of smooth muscle:
a. Inner layer = circular muscle; allows for constriction/dilation of the tract.
b. Outer layer = longitudinal muscle that shortens and lengthens tract.
Ø Stomach has a third layer that helps to churn stomach contents.
a. oblique layer = muscle located between the submucosal plexus and the
the circular layer.
Ø Contains the myenteric plexus (between the inner circular and outer
longitudinal), the second nerve network of the enteric nervous system.
Ø While most of the tract consists of these 2-3 layers, of smooth muscle, the
middle 1/3 of the esophagus contains both skeletal muscle and smooth
muscle to allow for some voluntary control of swallowing.

Similar to Figure 21.1

 C) Structure of GI Tract
Ø Tissue Layers of the GI tract wall:
4. Serosa
Ø Part of peritoneal membrane (peritoneum) lining the abdominal cavity.
Ø Composed of connective tissue and simple squamous epithelium.
Ø Forms sheets of connective tissue that help to hold organs in place.
Ø Also provides support for blood vessels and nerves going to/from
abdominal organs.

Figure 21.1
 D) GI Tract Motility
Ø Motility of the gastrointestinal tract is critical not only for Figure 21.4
moving material along the tube, but also for controlling the
conditions and amount of time available for adequate
digestion and absorption of nutrients.
ØContraction of smooth muscle in the GI Tract is of 3 types:
1. Peristalsis
Ø small, weak waves of contraction in which circular smooth
muscle contracts upstream from the bolus of food, while
muscle downstream (in front of bolus) relaxes. Result is bolus is
pushed further along the tube.
Ø In small intestine. – occurs as part of a reflex response
triggered by distension of intestinal wall
Ø The frequency of waves is efficient enough to move the
contents of the lumen.
Ø Transit time along the small intestine is ~2.5-6 hours
Ø Primarily controlled by myenteric plexus
D) GI Tract Motility Figure 21.4
2. Segmental contractions – mixes.
Ø Alternating contraction and relaxation of circular
muscle in adjacent sections of the intestine.
Ø Mixes up and churns the ingested material, which
ensures that it all gets exposed to the absorptive
surface (material from the middle of the lumen gets
moved to be in direct contact with the mucosa). And
also ensures exposure to digestive enzymes (mixing
distributes enzymes amongst the food particles for
digestion).
Ø Contributes very little to propulsion of the material
through the tube, since material is being moved
both backward and forward along the tube.
D) GI Tract Motility Figure 21.4
3. Migrating Motor Complexes (mass movements) –
Ø Similar to peristalsis but involves a larger/stronger wave of
contraction that propels the substance over a longer distance
(up to the entire length of the small and large intestines).
Ø These movements are a cleansing contraction that propel
undigested material as well as pathogens and bacteria out of
the small intestine and into the large intestine.
Ø Typically occur during or right after a meal (cleans out the
tube to get it ready to process the incoming food).
Ø Part of the gastrocolic reflex (a long reflex arc, also known as
the defecation reflex) which is initiated by distension of the
stomach or duodenum when consuming a meal. And is the
reason that people may feel the urge to defecate right after
(or even during) a meal, particularly breakfast. Any
physiological response after eating a meal is known as a
postprandial response.
 D) GI Tract Motility
ØAccelerated motility of the gut results in diarrhea, Figure 21.4
which is associated with increased frequency and
strength of migrating motor complexes.
ØDecreased motility results in constipation.
Constipation may lead to perforation of the large
intestine (a hole in the bowel). This causes the
release of bacteria and feces into the abdominal
cavity, and the resulting infection (sepsis) is often
life threatening (similar to a burst appendix).
 E) Regulation of GI Tract Motility & Secretion
ØInvolves both intrinsic control by the
enteric nervous system and local
signaling molecules (paracrines) and
extrinsic control by the
parasympathetic and sympathetic
branches of the nervous system and
hormones of the endocrine system.
ØInvolves reflex responses that are
integrated in both the enteric
nervous system (short reflexes) and
the central nervous system (long
reflexes). This includes any reflex
involving the brain (cephalic
reflexes).
Figure 21.5
E) Regulation of GI Tract Motility & Secretion
1. Neural Control
a. Enteric NS – “brain” of the gut; contains as many
neurons as the spinal cord and provides local intrinsic
control of motility and secretion. Involved in short
reflexes.
i. Submucosal plexus
Ø Located within the submucosal layer of the GI tract wall
Ø Controls functions associated with the mucosa
including: sensing the environment of the GI tract
lumen; regulating local blood flow; and controlling
Figure 21.1e
epithelial cells (including secretions from glands).
E) Regulation of GI Tract Motility & Secretion
1. Neural Control
a. Enteric NS – “brain” of the gut; contains as many
neurons as the spinal cord and provides local intrinsic
control of motility and secretion
ii. Myenteric plexus
Ø Located in the muscularis externa between the circular
and longitudinal layers.
Ø Controls GI motility by:
Ø Increasing smooth muscle tone
Ø Increasing the intensity of rhythmic contractions Figure 21.1e
Ø Increasing the rate of rhythmic contractions
Ø Increasing the velocity of peristaltic waves
Ø Decreasing sphincter muscle tone
E) Regulation of GI Tract Motility & Secretion
1. Neural Control
Figure 21.5
b. The Autonomic Nervous System
i. Parasympathetic Nervous System (PSNS)
Ø Involved in long reflexes.
Ø Activity of the PSNS increases most GI functions.
Ø The proximal gut is innervated by the vagus nerve
(controls the esophagus, stomach, pancreas, and
upper large intestine)
Ø As a result this nerve plays an important role in
deglutition (swallowing), vomiting gastric
emptying, and pancreatic secretion).
Ø The distal gut is innervated by the pelvic nerves which
control the remainder of the large intestine and
rectum and so help to control defecation.
Ø There is very little innervation of the small intestine, as
the activities carried out there are primarily regulated
by the enteric nervous system as well as hormones.
E) Regulation of GI Tract Motility & Secretion
1. Neural Control
Figure 21.5
b. The Autonomic Nervous System
ii. Sympathetic
Ø Involved in long reflexes.
Ø Activity generally decreases most GI functions.
Ø Involves spinal nerves from T5 to L2 that carry preganglionic
neurons to the autonomic sympathetic ganglia. Postganglionic
neurons then carry signals from the ganglia to all parts of the
GI tract
Ø The release of norepinephrine (noradrenaline) inhibits the
neurons of both the myenteric plexus and submucosal plexus..
c. Cognitive and Emotional Control
Ø There are neurological pathways connecting the senses and brain
with the stomach – cephalic reflexes (long reflexes).
Ø Feedforward reflexes in response to the sight, smell, thought of
food, increases acid production, motility and blood flow in the gut.
 E) Regulation of GI Tract Motility & Secretion
ØIntrinsic control GI Motility:
ØThe smooth muscle cells of the digestive tract have a resting Similar to Figure 21.4
membrane potential of -50 mV.
Ø Interstitial Cells of Cajal (ICC), act like pacemakers for the
contraction of gastrointestinal smooth muscle.
ØThey spontaneously produce slow waves of depolarization that
spread to adjacent smooth muscle cells through gap junctions.
ØThe cells slowly depolarize toward threshold (-40mV), and if
threshold is reached, action potentials (sometimes referred to as
spike potentials) and contraction will occur. The frequency of the
spikes determines the strength of the muscle contraction. Frequency
depends on the amount of depolarization. (Unlike cardiac
pacemaker potentials, each slow wave depolarization does not
always reach threshold, so the number of contractions produced
through these pacemaker cells is variable.
 E) Regulation of GI Tract Motility & Secretion
ØIntrinsic control GI Motility:
ØDepolarization of the Cajal cells can be stimulated by intrinsic
factors such as stretch in the smooth muscle cells (which allows
for greater entry of Ca++ during depolarization or extrinsic
factors including, parasympathetic stimulation via acetylcholine
(which opens ligand-gated Ca++ channels in the smooth
muscle cell membrane). .
ØRecall from BIOL2410 – Depolarization of smooth muscle cells
triggers calcium induced calcium release from the sarcoplasmic
reticulum. Ca++ then binds to calmodulin, which activates myosin
light chain kinase and initiates contraction.
ØHyperpolarization of the cells of Cajal (which can occur as a result
of stimulation by norepinephrine) results in no muscle contraction.

Figure 12.26
 E) Regulation of GI Tract Motility & Secretion
2. Chemical Signaling – more important in regulating the control of secretion than motility.
Ø Signaling molecules involved in digestion can act as hormones, or paracrine signaling molecules. Most
are peptides that bind to cell surface receptors on targets. They include:
a. Gastrin – released by G-cells of stomach in response to distension, the presence of peptides and amino acids,
and neuronal stimuli of G-cells.. Action= stimulate gastric (stomach) acid secretion
b. Cholecystokinin (CCK) – released by I- cells (a type of enteroendocrine cell) in the small intestine in response to
the presence of peptides and amino acids in chyme. Stimulates gall bladder contraction and emptying,
pancreatic enzyme secretion, and motility of the small intestine between meals. Inhibits gastric emptying and
acid secretion. Promotes satiety (feeling full after meal).
c. Secretin – released by S-cells (enteroendocrine) in the intestinal crypts (glands) of duodenum in response to the
presence of H+ in the chyme entering the duodenum from the stomach. Stimulates HCO3- secretion from duct
cells of pancreas and bile production in liver. Inhibits gastric (stomach) emptying and acid secretion.
d. Gastric Inhibitory Peptide – released by K-cells (enteroendocrine) in the duodenum and jejunum in response to
the presence of peptides, amino acids, glucose, and fatty acids in the chyme coming from the stomach. .
Stimulates insulin release from beta cells of pancreas (before there is a change in blood glucose levels). Inhibits
acid secretion, motility and emptying in the stomach.
 E) Regulation of GI Tract Motility & Secretion
2. Chemical Signaling – more important in regulating the control of secretion than motility.
Ø Signaling molecules involved in digestion can act as hormones, or paracrine signaling molecules. Most
are peptides that bind to cell surface receptors on targets. They include:
e. Glucagon-like Peptide GLP-1) – released by L-cells (enteroendocrine) of the small intestine in response to high
levels of glucose and fatty acids in the chyme passing through the small intestine. Stimulates insulin release from
pancreas and also acts on brain to promote satiety. Inhibits gastric acid secretion, gastric motility and gastric
emptying.
f. Motilin – released by M-cells in small intestine in response to neuronal stimuli. Stimulates migrating motor
complexes (motility) in the intestines and gastric emptying..
g. Histamine – released by enterochromaffin-like cells in stomach in response to the presence of amino acids and
peptides in the ingested food, and in response to neural stimulation.. Stimulates acid secretion.
h. Somatostatin – released by D-cells in stomach in response to high H+. Inhibits gastric stomach) acid secretion
and motility.
 F) Digestive Processes
Ø Each part of the digestive tract plays a role
in each of the four main digestive processes
(secretion, digestion, absorption and
motility).
ØThe activity in one section of the tract can
influence the activity in other parts of the
tract via neuronal or hormonal signaling.
ØThe overall process of digestion is
separated into 3 phases:
1. The Cephalic Phase
2. The Gastric Phase
3. The Intestinal Phase (which can be further
subdivided into events occurring in the
Figure 21.6
small intestine and the large intestine).
 G) Events of the Cephalic Phase
Ø Begins with feedforward reflexes (long reflexes) that
prepare the stomach and intestines for digestion.
ØSight, smell and thought of food stimulates the long
vagal reflex:
ØSensory neuron à medulla à preganglionic
parasympathetic neuron in vagus nerve à integration in
enteric plexus (submucosal for secretion, myenteric for
motility) à postganglionic parasympathetic and intrinsic
enteric neurons à target cells (secretion and motility)
ØTarget cells innervated by the submucosal plexus include
1. Mucous cells - secrete mucus that protects stomach
epithelium from hydrochloric acid (HCl).
2. Chief cells – secrete pepsinogen and gastric lipase,
which will digest protein and lipids respectively.
Pepsinogen, gastric lipase
3. Parietal cells – secrete HCl
4. G-cells – secrete gastrin.
 G) Events of the Cephalic Phase
ØDigestion begins in the mouth. Digestive processes include:
1. Secretion:
a. Saliva – mostly water with dissolved solutes.
2. Digestion:
a. Mechanical digestion – mastication (chewing) of food breaks it up
into smaller pieces and mixes the food with saliva.
b. Chemical digestion – Salivary amylase begins the breakdown of
complex carbohydrates (starch from plants and glycogen from
animals). The presence of lingual lipase to initiate the breakdown of
fat in the mouth is controversial, but it appears to occur at least in
some individuals. The exact source (whether produced by the
salivary glands, or other secretory glands or even microbes in the
mouth is disputed.).
3. Absorption:
Pepsinogen, gastric lipase
a. No nutrients can be absorbed.
b. Some drugs (e.g. nitroglycerin spray for the treatment of angina –
chest pain due to reduced blood flow to heart).
G) Events of the Cephalic Phase
ØDigestion begins in the mouth:
4. Motility :
a. Chewing
b. Swallowing (deglutition)

Figure 21.7
H) Events of the Gastric Phase Figure 21.9
ØInitiated by presence of food stomach – distension/
stretch (stimulates baroreceptors) and presence of
amino acids in food (stimulates chemoreceptors)
1. Secretion:
Ø gastric secretions are involved with digestion of
ingested material and protection of the stomach lining.
Ø The simple columnar epithelial lining of the stomach
has deep invaginations called gastric pits that contain
the gastric glands. These glands are formed from
multiple cells types, all of which produce secretions
involved in the gastric phase. They include:
a. Mucous cells – secrete mucus and/or bicarbonate
to produce a protective barrier against HCl. Mucus
acts as a physical barrier and bicarbonate acts as a
chemical barrier (neutralizes the acid that is in close
proximity to the wall of the stomach. .
H) Events of the Gastric Phase Figure 21.9
b. Parietal cells – secrete gastric acid (HCl) which plays a
role in protein digestion (denaturation and hydrolysis
of peptide bonds) and intrinsic factor which is
required for vitamin B absorption.
Ø Acid production involves:
i. A H+/K+ -ATPase pump in parietal cell apical (luminal)
membranes that pumps H+ out of the cell and K+ into
the cell.
ii. This establishes an electrical gradient (more positive
charge outside of the cell), and Cl- follows H+ down
the electrical gradient out of the cell through open
chloride channels.
iii. The same process that produces the H+ in parietal
cells also results in production of HCO3-. Unlike
mucous cells however, the HCO3- is released across
the basolateral membrane of the parietal cell in
exchange for chloride, It is then absorbed into the
blood. This increases the pH of blood leaving the
stomach after a meal – known as the alkaline tide.
H) Events of the Gastric Phase
c. Chief cells – produce pepsinogen (a proenzyme or
zymogen) involved in protein digestion and gastric lipase.
d. Endocrine cells:
i. Enterochromaffin-like cells (ECL cells) – secrete
histamine – acts on parietal cells to stimulate acid
secretion.
ii. G-cells – gastrin (acts on parietal cells to and chief cells
to stimulate HCl and pepsinogen secretion respectively)
iii. D cells – somatostatin
Ø Regulation of gastric secretion involves:
a. Presence of amino acids and neural signals from vagus nerve stimulate G cells. Figure 21.10
b. G-cells release Gastrin.
c. Gastrin (and signals from vagus nerve) stimulates secretion of histamine from ECL cells, and directly
stimulates parietal cells to release HCl.
d. Histamine stimulates HCl secretion by parietal cells (reinforces action of gastrin and PSNS signaling through
vagus nerve).
e. As pH of stomach drips, low pH inhibits release of gastrin (likely mediated by somatostatin from D-cells_
H) Events of the Gastric Phase
c. Chief cells – produce pepsinogen (a proenzyme or
zymogen) involved in protein digestion and gastric lipase.
d. Endocrine cells:
i. Enterochromaffin-like cells (ECL cells) – secrete
histamine – acts on parietal cells to stimulate acid
secretion.
ii. G-cells – gastrin (acts on parietal cells to and chief cells
to stimulate HCl and pepsinogen secretion respectively)
iii. D cells – somatostatin
Ø Regulation of gastric secretion involves:
a. Presence of amino acids and neural signals from vagus nerve stimulate G cells.
b. G-cells release Gastrin.
c. Gastrin (and signals from vagus nerve) stimulates secretion of histamine from ECL cells, and directly
stimulates parietal cells to release HCl.
d. Histamine stimulates HCl secretion by parietal cells (reinforces action of gastrin and PSNS signaling through
vagus nerve).
e. As pH of stomach drips, low pH inhibits release of gastrin (likely mediated by somatostatin from D-cells_
H) Events of the Gastric Phase
2. Digestion:
a. Mechanical digestion – churning of stomach
b. Chemical digestion – of fats and proteins.
Ø Protein – pepsinogen secreted by chief cells is activated by HCl,
which converts it to pepsin. Pepsin (an endopeptidase)
enzymatically breaks peptide bonds. It digests 10-20% of
ingested proteins while in the stomach. Products of pepsin
digestion are shorter polypeptides.
Ø Fats (Lipids) – minimal digestion by gastric lipase (<10%).
Enzymatically breaks down triglycerides into monoglycerides
and fatty acids.
Figure 21.18
3. Absorption:
a. Lipid soluble substances like alcohol and aspirin, but no absorption
of carbohydrates/amino acids, etc.
4. Motility:
a. Peristaltic mixing and propulsion..
 I) Events of the Intestinal Phase
Ø Chyme (mixture of gastric juice and partially digested food
from stomach) enters small intestine. Gastric emptying into
intestine is regulated so that 1) acid can be neutralized in the
small intestine; 2) tonicity does not overwhelm small intestine,
3) so that there is adequate time for digestion and.
absorption of nutrients.
ØThe structure of the of the small intestine, includes many villi
(projections of the submucosa into the lumen that contain
blood capillaries and lymph lacteals for absorption) is
specialized to maximize its absorptive surface area. Each villus
is lined with a simple columnar epithelium, whose cells all
have microvilli (which form the brush border, as they
resemble the tines on a brush)/comb). The Crypts (of
Liberkühn) are pits between villi that contain secretory cells.
Figure 21.11
 I) Events of the Intestinal Phase
Ø Events of the intestinal phase are initiated in response to
duodenal stretch and the presence of H+, amino acids and START

lipids in the chyme. The latter are detected by é HCO3- (alkaline fluid)

chemoreceptors that extend into the lumen from the

secretion from duct cells
é gallbladder
contractions & bile stimulates chief cells

submucosal plexus. release Inhibits: stomach

motility & secretions
(ê pepsinogen,
(é pepsinogen,
gastric lipase) and
parietal cells (é HCl)
lipase & HCl)

ØOverall process: Secretin

Food in the
1. Partially digested food enters the duodenum from the é Acid in
duodenum
stomach Gastrin

stomach.
a. The presence of H+ in chyme as it enters the duodenum CCK
é Secretion of
pancreatic
é bicarbonate (alkaline fluid)
secretion from duct cells

stimulates the S-cells in the intestinal crypts to release secretin. é Fatty acids,
enzymes

amino acids in
b. At the same time the presence of fatty acids and amino acids in duodenum

the chyme (as result of digestion that was carried out in the
stomach) stimulate I-cells in the intestinal crypts to release Figure 21.11
cholecystokinin (CCK).
c. The presence of carbohydrates in chyme stimulates the release of
GIP and GLP-1
I) Events of the Intestinal Phase
2. Actions of hormones:
a. Secretin
i. Stimulates duct cells of pancreas to secrete a watery, bicarbonate
(HCO3-) rich fluid that will act to buffer H+ in the chyme and raise the
pH to a value that is suitable for pancreatic enzyme action (~7.4)
ii. Acts on smooth muscle of stomach to inhibit motility and on cells in
gastric glands to inhibit secretion of pepsinogen, gastric lipase and
HCl. As a result, gastric emptying is slowed.
b. CCK Figure 21.20
i. Stimulates exocrine pancreas to secrete digestive enzymes (these are
really precursors to digestive enzymes called zymogens, that will be
activated in the duodenum).
ii. Stimulates gall bladder to contract and release bile into the bile duct.
iii. Also slows gastric emptying.
c. GIP and GLP-1 – both involved in feedforward reflexes that stimulate
release of insulin from pancreas. Both feedback to stomach to inhibit
events of the gastric phase.
I) Events of the Intestinal Phase
3. Inactive digestive enzymes (zymogens) are activated in the
intestinal lumen.
4. Mechanical and Chemical digestion of carbohydrates, fats,
polypeptides and nucleic acids takes place in the intestinal
lumen. Molecules are also further digested by brush border
enzymes (found on the surface of the microvilli of of intestinal
cells). (See notes in section J for digestion and absorption
details).
5. Absorption of the products of digestion.

Figure 21.11
J) Events of the Intestinal Phase
1. Secretion:
Ø During the intestinal phase, secretions are released by the pancreas, liver,
and gall bladder, in addition to the intestine itself. Mechanisms:
a. Secretion from crypt cells in the small intestine
i. Isotonic NaCl secretion
Ø Mixes with mucus sections from goblet cells to form a protective,
lubricating barrier on the apical surface of intestinal cells
(enterocytes).
Ø Chloride from ISF enters enterocytes via secondary active transport
through NKCC channels (similar to those we saw in the nephron).
Ø Chloride then diffuses into lumen of intestine through CFTR
channels (cystic fibrosis transmembrane conductance regulator
Figure 21.13
proteins – so called because mutations in the gene for this protein
cause cystic fibrosis)
Ø The electrical gradient established by Cl- leaving the cell causes
Na+ ions to diffuse out though the paracellular pathway. Water is
obligated to follow (osmosis), creating an isotonic saline solution on
the surface of cell.
I) Events of the Intestinal Phase
1. Secretion:
Ø During the intestinal phase, secretions are released by the pancreas, liver,
and gall bladder, in addition to the intestine itself. Mechanisms:
a. Secretion from crypt cells in the small intestine
ii. S-cells – acid in chyme stimulates secretion of secretin
iii. I-cells - fats and protein in chyme stimulates secretion of
Cholecystokinin (CCK)
iv. K-cells – carbohydrates in chyme stimulates secretion of
Gastric Inhibitory peptide (GIP)
v. L-cells – carbohydrates in chyme stimulates secretion of
Glucagon-like Inhibitory Peptide (GLP-1)
vi. M-cells – secrete Motilin (stimulates mass movements
in between meals)
Involved in either:
1. Regulating exocrine or endocrine secretions
from pancreas and/or gall bladder. Figure 21.20
2. Inhibiting gastric motility and secretions.
I) Events of the Intestinal Phase Figure 21.14
1. Secretion:
Ø Mechanisms of secretion in the intestinal phase:
b. Pancreas – consists of both endocrine and exocrine tissue
Ø Endocrine pancreas controls blood sugar levels
Ø Insulin (𝛽-cells) – promotes uptake of glucose by cells
Ø Glucagon (𝛼-cells) – causes breakdown of glycogen in
skeletal muscle cells and liver to mobilize more glucose
Ø Exocrine pancreas produces enzymes (in acinar cells) and
alkaline fluid (in duct cells) that are secreted via the
pancreatic duct into the lumen of the duodenum. Fluid plus
enzymes are collectively referred to as pancreatic juices.
Ø Alkaline fluid component, consists of K+, Na+,
bicarbonate ions and water. Neutralizes acidic chyme from
stomach. Increases luminal pH from ~3 to ~7. Bicarbonate
is produced by carbonic anhydrase (via the same process
we observed in red blood cells for respiration and
transport of CO2 and in tubule cells of the nephron for
reabsorption and secretion of bicarbonate ions.
I) Events of the Intestinal Phase Figure 21.14
1. Secretion:
Ø Mechanisms of secretion in the intestinal phase:
c. Liver – produces bile salts
d. Gall Bladder – stores and concentrates bile between meals, and
releases bile in response to signaling from CCK.
2. Digestion:
a. Mechanical – segmentation.
b. Chemical – digestion of carbohydrates, polypeptides, fats and
nucleic acids (details for each process in notes section J).
3. Absorption:
a. The small intestine is the site of most absorption of nutrients (see
notes section J for mechanisms of absorption for the different
nutrients).
4. Motility:
a. Segmental contractions for mixing.
b. Some peristalsis, but movement is slowed here to allow for
digestion and absorption of nutrients.
 J) Digestion and Absorption of Nutrients
Ø Once nutrients are mechanically and chemically digested, the
products must be absorbed and transported from the lumen of
the GI tract into the blood.
ØMost absorption occurs in the small intestine.
ØNot all nutrients require digestion, some can be absorbed as is
(ingested glucose, fructose, vitamins, minerals, etc.).
ØDigestive enzymes are produced and released by glands in the
superior portions of the GI tract – including salivary glands,
gastric pits, exocrine pancreas.
ØEnzymatic digestion starts in the mouth and continues through to

Enzyme actitivty
the small intestine, however different enzymes may work
optimally in different parts of the tract. For example, pepsin has a
pH optimum that allows it to function best in the low pH of the
stomach to function properly, trypsin requires the higher neutral
pH of the duodenum.
 J) Digestion and Absorption of Nutrients
ØIn addition to enzymes found in the pancreatic secretions,
the small intestine also has enzymes attached to the
epithelial brush border (for example enteropeptidase, which
is responsible for activation of trypsinogen into trypsin for
protein digestion). These enzymes play a critical role in
getting nutrients into a small enough form that can be
absorbed.
J) Digestion and Absorption of Nutrients
1. Carbohydrates
Ø Carbohydrates make up 50% of the average human diet and
include foods like bread, potatoes, pasta and rice as well as all fruits
and vegetables.
Ø Carbohydrates can be categorized based on the number of
monomers in their structure: polysaccharides
a. Polysaccharides (polymers of glucose) include:
i. Starch - is a polysaccharide used to store glucose in plants.
ii. Glycogen – is the storage form in animals (found in liver and muscle
tissue)
iii. Cellulose – is an indigestible plant structural material (also a
polysaccharide).
b. Disaccharides (composed of two carbohydrate monomers)
i. Sucrose (glucose-fructose)
ii. Lactose, the sugar found in milk (glucose-galactose) Figure 21.17
iii. Maltose (glucose-glucose) - maltose is also the breakdown product
of starch digestion.
J) Digestion and Absorption of Nutrients
1. Carbohydrates
Ø Carbohydrates make up 50% of the average human diet and
include foods like bread, potatoes, pasta and rice as well as all fruits
and vegetables.
Ø Carbohydrates can be categorized based on the number of
monomers in their structure: polysaccharides
c. Monosaccharides (carbohydrate monomers) are the only sugars that
can be absorbed by the intestine, meaning that all polysaccharides and
disaccharides must be enzymatically digested down to
monosaccharides before they can be absorbed. The most common
monosaccharides ((C6H12O6) are:
i. Glucose
ii. Fructose
iii. Galactose

Figure 21.11
J) Digestion and Absorption of Nutrients
1. Carbohydrates
Ø Carb Digestion:
a. Oral cavity
Ø Salivary amylase hydrolyzes polysaccharides like starch
(amylose) into disaccharides like maltose (dimer), and
oligosaccharides like maltotriose (trimer) and 𝛼-dextrin.
Ø Only 5% of starch digestion occurs in mouth
b. Stomach
Ø Gastric amylase - has a very minor contribution to
carbohydrate digestion. .
c. Duodenum
Ø Pancreatic amylase – powerful amylase that can completely
hydrolyze polysaccharides like starch into disaccharides and
oligosaccharides within 30 minutes. However not able to
breakdown ingested disaccharides like sucrose and lactose. Figure 21.17
J) Digestion and Absorption of Nutrients
1. Carbohydrates
Ø Carb Digestion:
c. Duodenum
Ø Pancreatic amylase – powerful amylase that can completely
hydrolyze polysaccharides like starch into disaccharides and
oligosaccharides within 30 minutes. However not able to
breakdown ingested disaccharides like sucrose and lactose.
Ø Brush border enzymes – enzymes (disaccharidases) bound to
the microvilli of the intestinal cells (enterocytes) complete the
digestion of disaccharides into monosaccharides: Includes:
Ø Sucrase

Ø Isomaltase

Ø Lactase
Figure 21.17
J) Digestion and Absorption of Nutrients
1. Carbohydrates
Ø Carb Absorption: Figure 21.17
Ø Only monosaccharides can be absorbed by the epithelium.
Ø Must cross the apical (luminal) and basolateral membranes of the
enterocytes before they can enter the blood.
a. At apical membrane :
i. Glucose and galactose are taken up by SGLT1 (sodium
glucose linked transporter-1).
Ø Na+ and glucose or galactose are cotransported into
the cell together (symport).
ii. Fructose is transported via facilitated diffusion using the
carrier protein GLUT5 (glucose transporter 5) .
b. At basolateral membrane:
i. Glucose, galactose, and fructose use facilitated diffusion to enter the ISF through a GLUT2 transport
protein (glucose transporter 2).
ii. Na+.K+ ATPase pumps in basolateral membrane establish concentration gradient needed for SGLT 1
cotransport in apical membrane (keeps concentrations of Na+ in the cell low, so that it can keep
moving into cell through SGLT1, down its concentration gradient carrying glucose/galactose with it).
J) Digestion and Absorption of Nutrients
1. Carbohydrates
Ø Fate of absorbed glucose/galactose/fructose::
Ø Galactose and fructose are converted to glucose
Ø Glucose is stored as glycogen in muscle and liver cells.
Ø Any any excess beyond the capacity of the muscles
and and liver are converted into lipids

Ø NOTE: Lactase deficiency results in lactose

intolerance. In most humans and other mammals,
expression of the lactase gene is downregulated
once an infant is weaned (i.e. lactose intolerance is
a normal result of switching to an adult diet). In
the absence of lactase, lactose passes through the
gut undigested and is fermented in the colon by
bacteria. This results in abdominal bloating,
flatulence, diarrhea, nausea, etc after consuming
dairy products.
 J) Digestion and Absorption of Nutrients
2. Proteins
Ø Protein digestion:.
a. Oral cavity
Ø Mechanical digestion only.. Mastication physically tears meat and
plant protein apart.
b. Stomach
Ø Hydrolysis by HCl – low pH denatures (unfolds) proteins and acid
hydrolysis breaks down the protein into peptides..
Ø Pepsinogen (a proenzyme) from chief cells is activated by HCl ,
converting it into pepsin.
Ø Pepsin enzymatically breaks peptide bonds. It is only
active in low pH environments (pH = 2 – 3).
Ø Pepsin digests 10-20% of ingested proteins while they
are in the stomach.
Ø Products of pepsin digestion are shorter
polypeptides. Figure 21.10
 J) Digestion and Absorption of Nutrients
2. Proteins
Ø Protein digestion:.
c. Duodenum
i. Pancreatic proteolytic enzymes are secreted into lumen – all
are proenzymes (zymogens) released from pancreas that
need to be activated in the lumen of the small intestine in
order to function. Includes:

Ø Trypsinogen

Ø Chymotrypsinogen

Ø Procarboxypeptidase
ii. A brush border enzyme, enteropeptidase, activates
trypsinogen to form trypsin.

trypsinogen trypsin
enteropeptidase
on intestinal wall
Figure 21.14
 J) Digestion and Absorption of Nutrients
2. Proteins
Ø Protein digestion:.
c. Duodenum
iii. Trypsin activates the pancreatic proenzymes, including trypsinogen
(which results in a positive feedback mechanism in which trypsinogen
promotes its own formation). The resulting active forms are referred to
collectively as proteases.

iv. Trypsin and Chymotrypsin act to cleave (cut) polypeptides in the

middle of the peptide chain (endopeptidases), while carboxypeptidase
removes amino acids from the carboxyl end of the polypeptide (and is
therefore considered an exopeptidase). Unlike carbohydrate digestion,
the proteases are non -pecific and act on a wide range of proteins. Figure 21.18
 J) Digestion and Absorption of Nutrients
2. Proteins
Ø Protein digestion:.
c. Duodenum
v. Products of digestion by proteases are dipeptides, tripeptides
and oligopeptides and a few amino acids.
vi. Brush border peptidases – enzymes embedded in apical
membrane of enterocytes including aminopeptidases and
dipeptidases digest the remaining oligopeptides into
tripeptides, dipeptides and amino acids.
vii. Once they are absorbed into the cytosol of the intestinal cells,
tripeptides and dipeptides are broken down into amino acids
by cytosolic peptidases.

Figure 21.18
 J) Digestion and Absorption of Nutrients
2. Proteins
Ø Protein Absorption:
Ø Amino acids, dipeptides, and tripeptides can be absorbed, intact proteins
cannot. One exception is the absorption of immunoglobulins (IgA) from
breast milk in neonatal infants (recall from Unit 4).
Ø Must cross the enterocyte membrane:
a. At apical membrane :
i. Amino acids are cotransported into the cell with Na+ (secondary
active transport)
ii. Di- and tripeptides are cotransported into the cell, with with H+.
Ø Once inside the cytosol, di- and tri-peptides are broken down
into amino acids by cytosolic peptidases.
iii. Some small peptides are transported across the intestinal cells via
transcytosis (endocytosis into the cell, and release via exocytosis
into the ISF/blood).
b. At basolateral membrane:
i. Amino acids are transported out of the cell by facilitated diffusion Figure 21.18
using carrier proteins.
J) Digestion and Absorption of Nutrients
 J) Digestion and Absorption of Nutrients
2. Proteins
Ø Fate of Absorbed proteins:
Ø Used for protein synthesis.

Figure 21.18
 J) Digestion and Absorption of Nutrients
3. Lipids
Ø The vast majority of dietary lipids are triglycerides (which consist
of three fatty acids attached to a glycerol backbone).
Ø Fats in the diet can be saturated or unsaturated.
Ø Saturated fats have fatty acids with single bonds between each carbon
atom and are saturated with hydrogen. These are solid fats at room
temperature, like butter, coconut oil., animal fats
Ø Monounsaturated fats have a single double bond between carbon
atoms. They include fats that are oils at room temperature, such as
olive oil as well as the oils in tree nuts like almonds..
Ø Polyunsaturated fats have more than one double bond between
carbon atoms. They include fats that are oils at room temperature,
such as the omega 3 and omega-6 fatty acids found in fish, eggs,
some tree nuts, etc.

Figure 21.11
J) Digestion and Absorption of Nutrients
3. Lipids
Ø Lipid digestion:.
a. Oral cavity
Ø Salivary lipase – short lived activity contributing very little to lipid
digestion. Lipase breaks down triglycerides into monoglycerides and
free fatty acids.
b. Stomach
Ø Churning helps to physically break up insoluble fats into large fat
droplets.
Ø Gastric Lipase – limited action, since without bile salts, can only act
on the surface of the large droplets.

Figure 21.16
J) Digestion and Absorption of Nutrients Figure 21.16

3. Lipids
Ø Lipid digestion:.
c. Duodenum
Ø Activation of pancreatic proenzymes (zymogens):
pancreatic juice contains procolipae and prophospholipase
which are activated into colipase and phospholipase by
trypsin. Pancreatic lipase is released in its active form.
Ø Emulsification – by bile salts breaks larger lipid droplets
into smaller ones and provides a larger surface area (50X
greater) for enzymatic digestion by pancreatic lipase.
Ø Pancreatic lipase – breaks down triglycerides into
monoglycerides and fatty acids.
Ø Colipase – bile salts block access of pancreatic lipase to fats
contained in emulsified lipid droplets. Colipase displaces
the bile salts to allow pancreatic lipase access to the lipids.
As such it is a cofactor that does not actually do any of the
enzymatic digestion itself.
Ø Phospholipase – breaks down phospholipids.
J) Digestion and Absorption of Nutrients Figure 21.16

3. Lipids
Ø Lipid digestion:.
c. Duodenum
Ø Micelle formation – Bile salts combine with phospholipids,
mono- and diglycerides, cholesterol and fatty acids to form
a “bubble” in which the insoluble products of digestion are
stored and transported called a micelle. Micelles have a
hydrophobic interior and hydrophilic exterior (due to
amphipathic bile salts and phospholipids) ) which helps to
keep the products of fat digestion in solution so that they
can be transported in close proximity to the enterocyte cell
membrane for absorption.
J) Digestion and Absorption of Nutrients Figure 21.16

3. Lipids
Ø Lipid Absorption:
Ø In order to be absorbed and transported in the body fluids,
lipids must be repackaged inside of the enterocyte.
Ø Steps:
a. At apical membrane :
i. Micelles carry products of fat digestion to apical
membrane
ii. Most fatty acids, monoglycerides, cholesterol,
enter the enterocyte via simple diffusion.
Ø Long chain fatty acid diffusion (>12 carbons
long) is mediated by fatty acid transporter
proteins (FATP4) located in jejunum and
ileum. *i.e. facilitated diffusion).
J) Digestion and Absorption of Nutrients
3. Lipids
Figure 21.16
Ø Lipid Absorption:
Ø In order to be absorbed and transported in the body fluids,
lipids must be repackaged inside of the enterocyte.
Ø Steps:
b. Inside of enterocyte::
i. Some fatty acids are combined with monoglycerides in
the smooth endoplasmic reticulum to reform triglycerides.
ii. Triglycerides are then combined with cholesterol and
apolipoproteins to form a chylomicron (a soluble package
of lipids) in the Golgi apparatus..
c. At basolateral membrane:
i. Chylomicrons (as well as fat soluble vitamins) exit enterocyte
via exocytosis.
ii. Chylomicrons are absorbed into lymph lacteals (package is
too large to diffuse into blood capillary). Transported in
lymph to the blood circulation (lymphatic thoracic duct
empties into left subclavian vein which drains into vena cava).
J) Digestion and Absorption of Nutrients
3. Lipids
Figure 21.16
Ø Fate of Absorbed lipids:
Ø Most lipids are stored in the adipose tissue cells::
a. At the membrane of the adipose cell triglycerides in chylomicron
are broken down by an enzyme called lipoprotein lipase (LPL)
into monoglycerides and fatty acids.
b. Monoglycerides and fatty acids move into the cells via simple
diffusion.
c. Once in the adipose cells, they are reassembled into triglycerides
for storage.
d. Empty chylomicron packages are recycled in the liver.
J) Digestion and Absorption of Nutrients
Summary of lipid (fat) digestion and absorption
 K) Absorption of Water
Ø Water enters the GI tract through ingested fluids and foods,
as well as through secretions from the GI tract itself.
Ø~ 2.0 L/day ingested
Ø~6.5-7.0 L/day from secretions (saliva, bile, gastric secretion, pancreatic
secretions, intestinal secretions).
ØTotal = 8.5 – 9.0 L/day

Ø Most (~90%) of water reabsorption occurs in the small

intestine via osmosis (~7.5 L/day).
Ø Only 9-10% (~ 1-1.4 L) is reabsorbed by the large intestine,
but this reabsorption is important for feces formation.
• Poor uptake = wet stool (diarrhea) - can lead to severe dehydration and
death
• Too much uptake (slow movement of feces) can lead to constipation.

Ø Less than ~1% (~100 mL) of ingested/secreted water is

excreted with the feces per day.
Figure 21.3
 L) Elimination of Wastes (Defecation)
Ø Defecation Reflex (rectal reflex) Impulses from
cerebral
cortex
Ø Stimulus is presence of feces in rectum (activates stretch (conscious
control)

receptors in rectal wall)

Sensory
nerve
fibers
Ø Signals are integrated in the sacral segment of spinal cord
(PSNS) Voluntary
motor
nerve to
external
Ø Effector is smooth muscle of the rectum which contracts, anal sphincter
Sigmoid
and pressure from the feces causes the internal anal colon

sphincter to relax and open.

Stretch
receptors in
Ø External anal sphincter is skeletal muscles that is under wall

voluntary control (i.e. not part of reflex) so that you can Rectum
External anal
decide when and where is an appropriate time to defecate. sphincter
(skeletal muscle)
Involuntary motor
nerve
(PSNS)
Internal anal
sphincter
(smooth muscle)

Marieb and Hoehn 2018.