Gastrointestinal

Physiology
Mrs C Mahachi

1
 Assignment 1
Describe the effect of carbohydrate intake on GIT
processes.

Note the GIT processes include secretions, motility or motions,

digestion and absorption(and general utilization of nutrients) .
Total marks is 25 marks
Due on the 10 th of April at 23:59 hours (note if it arrives
in my mail box after the above time there is a 5 mark
deduction for each day it comes late)

2
 Assignment 2
Describe how typhoid and cholera affect the GIT and
the complications associated with these infections.

Total marks is 25 marks

Due on the 17 th of April at 23:59 hours (note if it arrives
in my mail box after the above time there is a 5 mark
deduction for each day it comes late)

3
 Assignment 3
Using the document attached entitiled “Calculation
of the nutritional value of a meal”, list foods you
would have eaten from the time you wake up to the
time you go to bed. Include the weights of the foods
you would have eaten. From these conduct the
exercise on the above attached document for the meal
you would have eaten for lunch.

4
 Objectives of GIT course
General Instructional Objective

An understanding of basic gastrointestinal physiology

and it’s application
Motility
Digestion
Secretion
Absorption and general utilization of nutrients
Elimination/defecation
 Objectives-Required Abilities
a. To outline the neural and hormonal regulation of
secretions from the gut

b. To outline the secretions from the gastrointestinal tract

including saliva, gastric fluid, bile, pancreatic fluid and
intestinal fluid

c. To outline basic aspects of fat, protein, and carbohydrate

digestion and absorption. This includes assimilation of
vitamins and minerals

d. To describe the control of gastric motility and emptying

e. To describe the physiology of swallowing, vomiting and
various movements in the GIT
f. To describe regulation of intake and factors associated with it
g. The colony within the gut and its relation with your health
h. To describe the consequences of prolonged vomiting,
gastrinomas and malabsorption syndromes
i. Describe the composition of a balanced diet and the
nutritional value of food.
 Introduction
The GI tract is a portal through which nutritive
substances, vitamins, minerals and fluids are
absorbed
Digestion and absorption occur primarily in the
small intestine
Digestion involves enzymes from
Salivary and lingual glands (CHO and fats)
Stomach (proteins and fat)
Pancreas (proteins, fats, CHO, DNA/RNA)
Action of enzymes aided by HCL and bile
There are basically three phases of digestion and
absorption
The Luminal
Digestion of large molecules
It is affected by motility or stasis (Mechanical digestion)

Mucosal
Enzyme mediated digestion of smaller products eg disaccharides
Also involves the process of absorption

Post absorptive state

The metabolic state achieved after complete digestion and
absorption of a meal.
Digested products in the body, either in lymph or blood
Digestive and absorptive functions
depend on a variety of mechanisms
These mechanisms
Softening of food (mastication)
Propulsion of food through the gut
Mixing of food with the secretions

All this is dependent in turn on reflexes

Intrinsic to the gut
Involving the CNS
Paracrine effects of chemical messengers and GI
hormones
Organization of the GIT.
 Accesory organs

1. Salivary glands

2. Liver and gallbladder

3. Pancreas
Functions of Gastrointestinal organs
Summary of motility, secretion, digestion, and absorption in
different regions of the digestive system
 Functions of GIT
Function defined by the following processes
Motility: movement through the GI tract
Digestion: breakdown of food
Secretion and : across the epithelial layer into the GI
tract (secretion)
Absorption: across the epithelial layer into the blood
(absorption)
Storage and elimination
Other activities by the GIT
 Other functions of GIT
Immune Response
Produces acid (pH 1-3)in stomach which gives an
inhospitable environment for microorganisms
There are microorganisms that kill pathogenic
microorganisms (Probiotics)
GALT (gut-associated lymphoid tissue). Peyer’s
patches are a component of GALT found in the lining
of the small intestines.
Peyer’s patches (which are secondary lymphoid tissue) and
other gut-associated lymphoid tissue contain macrophages,
dendritic cells, B-Lymphocytes, and T-Lymphocytes.
Cytokines can influence GIT movement
Some increase
Some decrease
 GALT
About 70% of the body's immune system is
found in the digestive tract
Tonsils (Waldeyer's ring) Back of pharynx
Adenoids (Pharyngeal tonsils)
Peyer's patches
Lymphoid aggregates in the appendix and large
intestine
Small lymphoid aggregates in the oesophagus
Lymphoid tissue accumulates with age in the stomach
Diffusely distributed lymphoid cells and plasma cells
in the lamina propria of the gut
GALT
 Physiological anatomy of the GIT
wall
4 layers of the GIT Wall
Mucosa
Submucosa
Muscularis
Serosa
 Mucosa
Concerned with
secretion of digestive juices
secretion of certain hormones
absorption of the various nutrients.

Layers
Epithelial layer – made up of columnar cells
Contains endocrine gland cells and exocrine gland cells and cells
specialized for absorption of digested nutrients
Lamina propria- connective tissue layer
Houses GALT
Muscularis mucosa – smooth muscle layer
Circular and longitudinal muscle
 Mucosa
It contains blood capillaries, lymph vessels.
Generally highly folded to increase surface area for
absorption
Ridges and valleys

Degree of folding varies with region of tract

Greatest in the small intestine

Pattern of folding can be modified by contraction of

the muscularis mucosa
Rugae in the stomach
 Submucosa
This is a dense/thick connective tissue layer

Provides distensibility and elasticity

contains
larger blood
lymph vessels
network of neurons called submucous or Meissner’s
plexus.
 Muscularis externa
Major smooth muscle coat of the GIT
An outer longitudinal layer and inner circular layer of
smooth muscle.
In between myenteric or Aurbach’s plexus.

Contraction of circular muscles decreases diameter of the

lumen
layer prevents food from traveling backward as in peristalsis.

Contraction of longitudinal muscles shortens tube

Facilitate peristalsis by reducing circular muscle tension

Contraction of both muscles provides propulsive and

mixing motions.
 Serosa
A smooth tissue membrane consisting of
two layers of mesothelium
secretes serous fluid

Lubricates and prevents friction between

digestive organs and surrounding
viscera
 Structure of the GIT Wall
Villi –
fingerlike projections extending from luminal surface
of small intestine: each villi surface is covered with
layer of epithelial cells whose surface membranes
form small projections called microvilli or the
brush-border.
This combination of folded mucosa, villi, microvilli
increases small intestine surface area 600-fold.

Total surface area of human small intestine is 300

m2 = area of tennis court

24
Intestinal Villi
 Epithelial renewal
Three main populations of cells in GIT epithelial cell population
Absorptive enterocyte is majority of cell population
highly polarized columnar cell
Goblet cells secrete mucus
Enteroendocrine cells secrete a variety of hormones

Epithelial cells continuously renewed every 4–5 days through a

process of renewal and migration.

Proliferative cells (stem cells) reside at the crypt base of the

intestinal glands (epithelial invasions into the underlying connective
tissue)
the new cells migrate upwards and out of the crypt.
In the normal healthy gut, the enterocytes migrate to the top of the villi
in in 1-4 days, meaning that all of the villi cells are replaced with new
cells every 3-5 days (this gets slower as we age)
The cells that migrate toward the bottom of the crypts have a longer
lifespan of 2-3 weeks
17 billion cells replaced daily

A defect in cell production

leads to the development of
mucosal atrophy and results
in a decrease in absorption

Mucosal hyperplasia results

from excess production of
newborn cells. Hyperplasia
can cause hypersecretion and
increase the risk of cancers
 How each GIT section is
divided
Intestinal tract functionally divided into segments by
sphincters

Helps restrict the flow of intestinal contents to

optimize digestion and absorption
Sphincter Locations

29
A. Upper Esophageal Sphincter (UES):
Made up entirely of skeletal muscle.
under tonic stimulation between swallows. Upon swallowing, the UES relaxes,
allowing the food to move from the mouth and pharynx into the esophagus.

B. Lower Esophageal Sphincter (LES):

made entirely of smooth muscle
separates the esophagus from the proximal stomach.
The function of the LES is critical to preventing stomach acid from refluxing up
into the esophagus.

C. Pyloric Sphincter:
the distal stomach from the small intestine (duodenum).
regulates gastric emptying.
Dysfunction of the pyloric sphincter causes dumping of a high acid load into the
small intestine
may lead to duodenal ulceration and problems with digestion.
D. Ileocecal Sphincter (Valve):
regulates the flow of food material from the small intestine into the large intestine.
Activity in this sphincter limits the movement of bacteria from the cecum to the ileum.
An incompetent sphincter is associated with intestinal bacterial overgrowth and
malabsorption.

E. Internal Anal Sphincter (IAS):

composed of smooth muscle
is important for initiating the defecation reflex.
Distension of the walls of the rectum cause the IAS to relax to facilitate defecation.

F. External Anal Sphincter (EAS):

is composed of striated muscle
therefore is under somatic (voluntary) control.
the initiation of a defecation reflex by stretch of the IAS can be overcome through
contraction of the EAS, a learned behavior (toilet training).
Sphincter of Oddi, or Glisson's sphincter
controlling secretions from the liver, pancreas and gall
bladder into the duodenum
Regulation of the GIT
Three major mechanisms that regulate and
control digestive activities
Neural Regulation
 Neural regulation

Enteric Nervous Extrinsic nervous

system system

• Internal/intrinsic nervous system • Autonomic nervous system

• Local nervous system (mini brain) • Central nervous system
• can work independent of
Extrinsic nervous system
 Enteric nervous system
constituents
Made up of
Myenteric plexus (Auberchs’s plexus)
Meissner plexus (submucosal plexus)
Neurons either synapse with other neurons or end
near muscles, glands and epithelial cells.
Enteric nervous system contains
adrenergic and cholinergic neurons
nonadrenergic & noncholinergic neurons that release
neurotransmitters e.g NO, CO, serotonin, GABA, ATP & several
neuropeptides
Cross-section (myenteric/Submucosal)
39
 Myenteric and Meissner
Plexus
Many axons leave the myenteric (Auberch’s) plexus
and synapse with neurons in submucosal (meissner)
plexus and vice-versa.
Neural activity in one plexus influences the activity
of/in the other
Stimulation at one point in plexus leads to impulses
conducted both up and down tract.(stimulation of
small intestine can affect smooth muscle and gland
activity of stomach – law of the gut)
Myenteric (Auberch’s) plexus influences smooth
muscle

Submucosal plexus (Meissner) influences secretory

activity

Many effectors (muscle cells, exocrine glands) are

supplied by neurons that are part of the ENS & this
allows neural reflexes that are completely within the
tract independent of the CNS
Extrinsic and intrinsic control of
gastrointestinal motility.
The extrinsic (autonomic nervous system) sympathetic and
parasympathetic supply to the GIT modulates the function
of the enteric brain located in ganglionated plexi along the
gastrointestinal tract.
Paraympatheic cholinergic activity increases intestinal
smooth muscle
Sympatheic noradrenergic activity decreases activity while
causing sphincter contraction

Transmitters released from the enteric neurons, which are

the intrinsic neural control of the gut, modulate the
peristaltic reflex.
 Autonomic nervous system and
Central nervous system influence
Nerves fibres from both the parasympathetic and sympathetic
enter the intestinal tract and synapse with neurons in the
myenteric and meissner plexus.
Preganglionic parasympathetic fibres consist of ~2000 vagal
efferents and other efferents in the sacral nerves
End on cholinergic nerve cells of the plexus

Sympathetic fibres are postganglionic

Most end on postganglionic cholinergic neurons
Epinephrine secreted inhibits acetylcholine secetion by activating
α2 presynaptic receptors
Others end directly on intestinal smooth muscle
Others cause vasoconstriction of blood vessels

CNS can influence GIT motility and secretory activity

 Gastrointestinal Smooth
Muscle
Smooth muscle effect GIT movement

Single-unit (gap junctions, coordinated contraction)

Activated/inhibited by many neurotransmitters,

hormones

Contraction can be tonic (sustained contraction) or

phasic depending on location/purpose of muscle cells
Sphincter vs. GIT Wall
Smooth muscle layout of the GIT
Individual smooth muscle fibers in the gastrointestinal tract are
200 to 500 micrometers in length
2 to 10 micrometers in diameter,
arranged in bundles of as many as 1000 parallel fibers.

Each bundle of smooth muscle fibers is partly separated from the

next by loose connective tissue
The muscle bundles fuse with one another at many points,
so that in reality each muscle layer represents a branching
latticework of smooth muscle bundles.
each muscle layer functions as a syncytium (when an action
potential is elicited anywhere within the muscle mass it generally
travels in all directions);
SMOOTH MUSCLE OF G.I.-Contractions
Phasic contractions

- periodic contractions followed by relaxation; such as in

gastric antrum, small intestine and esophagus

Tonic contractions

- maintained contraction without relaxation; such as in orad

region of the stomach, lower esoghageal, ileocecal and
internal anal sphincter

- not associated with slow waves

46
SMOOTH MUSCLE OF G.I.
Tonic contractions (continued):
- Caused by:
• Continuous repetitive spike potential
• Hormonal effects
• Continuous entry of Calcium

47
The Musculature of the Digestive
Tract

Three main muscle layers:

Longitudinal muscle layer
Circular muscle layer
Oblique muscle layer (stomach only)

48
The Musculature of the Digestive
Tract
Longitudinal Muscle:
Contraction shortens the segment of the intestine
and expands the lumen
Innervated by ENS, mainly by excitatory motor
neuron
Calcium influx from out side is important

49
The Musculature of the Digestive
Tract
Circular muscle:
Thicker and more powerful than longitudinal
Contraction reduces the diameter of the
lumen and increases its length
Innervated by ENS, both excitatory and
inhibitory motor neurons
More gap junctions than in longitudinal
muscle
Intracellular release of Calcium is more
important
50
 Smooth Muscle Excitation/Contraction
Coupling
Slow Waves cause
“Spike Potentials” during
Ach stimulation
Spike (Action) Potentials
lead to increased [Ca2+]
[Ca2+], hormones
(through PIP2 pathway)
activate MLCK
phosphorylates MLC
 Coupling Trigger Contractions in GI
Muscles

Depolarization opens the voltage-gated Ca channels

(electromechanical coupling)

Ligands open the ligand-gated Ca channels

(pharmacomechanical coupling)

52
 Long and short neural
reflexes
Most reflexes are initiated by luminal stimuli
Distension
Osmolarity
Acidity
Digestion products

Other stimuli
Hunger
Sight
Smell
Emotional state
Long and short reflex pathways can be activated by
stimuli in the GIT.
Long reflexes utilize neurons that link the central
nervous system to the GIT
Short reflexes mediated by the enteric NS to effector
cells
CNS & Enteric Nervous System (ENS)
Movements/Propulsion/mixing of
food in the GIT
Movements/Propulsion/mixing of
food in the GIT
Basal Electrical Rhythm
Peristalsis

Migrating motor reflex

Segmentation contraction

Mass action contraction

 Peristalsis
Basic propulsive movement of the GIT.
Reflex response that is initiated when the gut wall is
stretched by contents of the lumen, occurs in all parts of GIT
from the esophagus to the rectum.
1 peristaltic wave takes about 9 seconds
Rate varies from 2 – 25 cm/s

If a large particle does not reach the stomach in the first

contraction a second wave occurs due to the distension caused
by the food particle lodged in the oesphagus
↑ or ↓ in rate can be caused by autonomic input to the gut
Peristalsis
•Cholinergic neurons passing in
retrograde direction in myenteric
plexus activate neurons that release
substance P and acetylcholine
causing smooth muscle contraction.

•At same time, cholinergic neurons

passing in an anterograde
direction activate neurons that
secrete NO, VIP & ATP producing
the relaxation ahead of stimulus
 Peristalsis contd
Local stretch by ingested contents initiates a
circular contraction behind the stimulus & an
area of relaxation in front of it & wave of
contraction moves in an oral to caudal direction
propelling contents forward at rates between 2
– 25 cm/sec.
It is autonomic & independent of extrinsic
influence. Stretch receptors activate Serotonin
release which activates sensory neurons to
activate myenteric plexus
The major transmitters in the peristaltic reflex are:
acetylcholine (ACh) and substance P (SubP) are the
predominant excitatory neurotransmitters,
vasoactive intestinal polypeptide (VIP) and nitric oxide
are the predominant inhibitory neurotransmitters.
 Model of the intestinal peristaltic reflex in the mouse.

John R. Grider J Pharmacol Exp Ther 2003;307:460-467

The American Society for Pharmacology and Experimental Therapeutics

 Basic Electrical Rhythm(Slow
waves)
Spontaneous rhythmic a wave of depolarization &
repolarization or fluctuations in membrane potential
between –65 and –45 mV.
originates from pace-maker cell (Interstitial cell of Cajal) at
a rate of one/ 20 sec
exception - esophagus & proximal portion of stomach.
Responsible for producing gastric peristaltic waves
In stomach it is located in outer circular layer near
myenteric plexus & in colon at submucosal border of
circular muscle layer.
Slow Waves & GI Contractions
Action potentials fire
Action potential When slow wave
Slow Potentials exceed
wave threshold
Threshold

Force & duration of

muscle contraction -
directly related to
amplitude & frequency
of action potentials

64


Basic Electrical Rhythm Figure 21-3
 Basic Electrical Rhythm
Waves are conducted through gap junctions along the GIT
Action potentials may be generated at peak of slow wave if
threshold is produced.
BER affected by many neurotransmitters & polypeptides
e.g.: acetylcholine increases number of spikes & smooth
muscle tension where as norepinephrine has opposite effects.
Rate of BER = 4/min in stomach; 12/min in duodenum;
8/min in distal ileum; 9/min in cecum & 16/min in sigmoid;
contraction occurs only during depolarizing waves
The frequency of BER is
Increased by gastrin, vagal stimulation and gastric distension
(law of the gut)
Decreased by sympathetic stimulation, duodenal distension
(law of the gut), fast and acids
 chain kin ase or Ca -
of inputs from e nte ric motor ne urons
■ Ga s trointe s tina l motility pa tte rns a re highly inte grate d be haviours re quiring
ing Rho-kin ase, integ
coordination be twe e n s mooth mus cle ce lls a nd utilizing re gula tory inputs from interactin g protein ki
inte rs titia l ce lls , ne urons , a nd e ndocrine a nd immune ce lls increasing level of cytop
■ The ra pe utic re gula tion a nd tis s ue e ngine e ring of ga s trointe s tina l motility is physiological event th
proving difficult kinase. Phosphorylatio
binding to actin, initi
force development. ML
traction are balanced by
(MLCP). MLCP is com
CNS of these subunits (myo
MYPT) anchors MLCP
Mye nte ric ple xus targets a 37 kDa catalyt
Effe re nt ne urons nine phosphatase, PP1c
of MYPT (see below) ca
between phosphorylated
therefore, regulation of
for modulating the forc

Exc it a t ion–c ont ra c t

Ma cropha ge
Affe re nt Studies of sever al spe
ne urons concept of excitation–c
Ente ric motor lian gastrointestinal sm
ne urons
Ma s t have also demonstrate
ce ll Eicos a noids Nitric oxide
expression of ionic con
His ta mine
Eicos a noids
and in different region
The ionic channels in h
muscles responsible for
ICC PDGFRα+
ce ll and the specific respon
SIP
transmitters and other
s yncytium studied in enough dept
contraction coupling m
testinal smooth muscl
Hormone s
are described below, in
SMCs other smooth muscle ty
Blood ve s s e l
of laboratory animals.

In t e g r a t e d m o t o r b e h a v i o u r Volta ge-de pe ndent ca

Figure 1 | Re gula tion of ga s trointe s tina l motility. Ma jor fa ctors involve d in
Like all excitable cells,
re gula tion of the tunica m uscularis of the ga s trointe s tina l tra ct. SMCs a re s hown in in gastrointestinal mus
+
 SLOW WAVES
Occur at different frequency
4/min in stomach;
12/min in duodenum;
8/min in distal ileum;
9/min in cecum
16/min in sigmoid;

- May or may not accompanied by AP

The slow waves do not cause calcium ions to enter the
smooth muscle fiber (only sodium ions)

During the spike potentials, generated at the peaks of

the slow waves,
action potentials occur
significant quantities of calcium ions do enter the
fibers and cause most of the contraction.
Depolarisation is due to Calcium influx and
repolarisation is due to potassium efflux
 Smooth Muscle Excitation/Contraction
Coupling
Slow Waves cause “Spike
Potentials” during Ach
stimulation
Spike Potentials lead
to increased [Ca++]
[Ca], hormones (through
PIP2
pathway)
activate MLCK
phosphorylates MLC
 Slow Waves & Action potentials are
Forms of Electrical Activity in GI Muscles
 Factors that depolarize the membrane:
Stretching of the muscle
Ach
Parasympathetic stimulation
Hormonal stimulation

 Factors that hyperpolarize the membrane:

Norepinephrine
Sympathetic stimulation
71
 Migrating Motor Complex
(MMC)
Occurs only during fasting
Cycles of motor activity from stomach to distal ileum
Each cycle/MMC has 3 phases
Phase I – quiescence
Phase II – electrical and mechanical activity
Phase III – burst of regular activity
MMC migrates aborally at a rate of 5cm/s at intervals
of 90 mins
MMC increases pancreatic secretions and increase
bile flow
They stop immediately after ingestion of food
 Migrating Motor Reflex
Motilin
Secreted by Endocrine cells in small intestine
Target is Smooth muscle of antrum and duodenum

Stimulates migrating motor complex

Stimulus for release is fasting: periodic release every
1.5-2 hours by neural stimulus
 Segmentation
Mixing motion in the small and large intestine
Ring like contraction that appear at fairly regular
intervals along the GIT, which then disappear & are
replaced by another set of contractions.
Contractions move chyme to & fro, increasing
exposure to the mucosal surface, thereby facilitating
absorption
Segmentation
 Mass action contraction
Simultaneous contraction of smooth muscle over a
large confluent area, moving material from one
portion of colon to another

They may also move material into the rectum.

Rectal distension intiate the defecation reflex

Interactive motile events
(reflexes)

Law of the intestine- the

intrinsic contractile wave in
response to bolus of material
Distension in one segment affecting activity in
another segment
 Interactive motile events
(reflexes)
1. Intestino-intestinal reflex
Overdistension of one segment causes relaxation in
the rest of the intestine
2. Ileogastric reflex
Ileal distension leads to decrease gastric motility
3. Gastroileal reflex
Increased gastric activity causes increased ileal
motility & movement through ileocecal sphincter
4. Gastrocolic and duodenocolic reflex
Increased gastric and duodenal distension increases
colon motility
 Neuromodulators and
neurotransmitters of the ENS

79
 Types of Neurotransmitters
neuromodulators secreted by
Enteric Neurons
Acetylcholine
Norepinephrine .
adenosine triphosphate,
serotonin,
dopamine,
Cholecystokinin (CCK),
Substance P,
vasoactive intestinal polypeptide (VIP),
somatostatin,
leu-enkephalin and met- enkephalin,
Bombesin/Gastrin releasing Peptide (GRP)
Endothelin 2
Thyrotropin releasing hormone (TRH)
Neurotensin
Peptide YY
Neuropeptide Y
 Class exercise
During the Easter break you either ate or cooked a
meal. Describe the movements along the GIT that
took place on
1. Smelling or hearing the preparation of food
2. When you ate the food
Hormonal Regulation
 Hormones
Each hormone participates in a feedback control
system that regulates some aspect of the GI
luminal environment
Each hormone affects more than one type of
target cell
In many cases a single effector cell contains
receptors for more than one hormone,
Receptors for neurotransmitters and paracrine agents
 Hormones cotd
A variety of inputs affect the cell’s responses i.e.
Synergism of inputs can potentiate responses
e.g.  Secretin stimulates pancreatic bicarbonate secretion,
whereas  CCK has a weak stimulus of bicarbonate
secretion
Therefore a stronger stimulus than one stimulus

Therefore consequence of potentiation is that small

changes in the plasma concentration on GI hormone
can have large effects on the action of other GI
hormones
GI hormones also have trophic effects
 Enteroendocrine cells
More than 15 types of cells in mucosa of stomach, small
intestine and colon
Many secret one hormone
Some secret either serotonin (enterochromaffin cells) or
histamine (enterochromaffin like cells [ECL cells])
Neuroendocrine cells

These cells are classified as amine precursor uptake and

decarboxylation (APUD) cells
APUD cells are a group of apparently unrelated cells that secrete
most of the body's hormones, with the exception of steroids
they manufacture amines in addition to polypeptides
 Hormone production sites

G
 Peptide families
Gastrin Family Secretin Family
CCK Secretin ,Glucagon,
GIP, VIP, GLP17-36
Gastrin

Pancreatic polypeptide
Family Other
Pancreatic GRP, Motilin
polypeptide Guanylin,
Substance P
Neuropeptide Y Neurotensin
Somatostatin
Peptide YY
Hormones of the GIT
 Gastrins
Big (34 AAs), small (17AAs), mini (14AAs) and a big big gastrin
(45AAs – can be secreted by some gastrinomas)
Actions ( short term - small gastrin mainly)
Stimulate acid/pepsinogen secretion
Increase gastric blood flow
Contraction of circular smooth muscle
Long Term (big gastrin)
Trophic to stomach, intestine, pancreas
Other effects
Water and electrolyte secretion
Acts on CCK B receptors
Stimulates calcitonin secretion
stimulates pancreatic somatostatin secretion
Stimulates insulin and glucagon secretion (Protein meal)
 Gastrin peptide chains
vs
CCK peptide chain

https://doctorlib.info/physiology/medical/222.html
http://163.178.103.176/CasosBerne/6fDigestivo/Caso33-1/HTMLC/CasosB2/Zollinger/Gastrina4.htm
https://www.studyblue.com/#flashcard/view/1101240
 Stimuli that affect gastrin
secretion
Increase secretion Decrease secretion
Luminal Luminal
Peptides and amino acids Acid
Distension
Somatostatin
Neural
Vagal stimulation Blood borne
Secretin
Blood borne GIP
vagal discharge
VIP
Calcium
Glucagon
Epinephrine (β2
receptor) calcitonin
It also inhibits
Gastric emptying
Absorption of glucose and electrolytes
Secretion increased by
parasympathetic through vagal stimuli, distension,
hypercalcemia, peptides, AAs
Conditions associated with increased gastrin, are
achlorydia, vagotomy, Zollinger Ellison syndrome, Chronic
renal failure ( deactivates gastrin and PTH), massive small
bowel resection and Rheumatoid arthritis
Secretion inhibited by
Acid (by negative feedback of increased acid), VIP, GIP,
somatostatin, secretin, glucagon, calcitonin
 Cholecystokinin
58AA, 39AA, 33AA and 12AA peptides secreted
by I cells in duodenum and jejunum
CCK is found in nerves in the distal ileum and colon

Last 58 AA (functional part) similar to gastrin,

hence both hormones have similar functions
Present in the intestines
Enteric and pancreatic nerves contain 4AA
CCK8 is a potent neurotransmitter
58AA and 8AA also found in the brain
Stimuli increasing secretion
L amino acids especially tryptophan
Acid
Fat
CCK-releasing peptide (intestinal muscosa) and
monitor peptide (pancrease)
Positive feedback mechanisms available
 CCK Stimulation

Mechanisms responsible for controlling the release of cholecystokinin (CCK) from duodenal I cells. ACh, acetylcholine; CCKRP, CCKreleasing pep
represent stimulatory effects, whereas dashed arrows indicate inhibition. Redrawn from Barrett KE: Gastrointestinal Physiology. New York, McGraw
Actions (on CCK A receptors)
Contraction of GB, relaxation of sphincter
Enzyme, bicarbonate secretion by pancreas
Slows gastric emptying
Trophic on pancreas
increases the synthesis of enterokinase,
may enhance the motility of the small intestine and colon.

Other
Stimulates acid secretion (weakly hence blocks action of gastrin
reducing its effects therefore very low acid secretion) (CCKB gastrin
receptor)
Stimulates glucagon and insulin secretion after protein meal
Pepsinogen secretion, feeding behaviour
Increase calcitonin secretion
Stimulates duodenal and pancreatic somatostatin secretion
 Secretin
1st hormone to be discovered (Starling)
27AA peptide, mimics glucagon in pharmaceutical
doses
Secreted by S cells in duodenum
Acts synergistically with CCK
Stimuli increasing secretion (acid)
Actions
Decrease acid secretion, gut motility, inhibit action of LES,
release insulin
Cause lipolysis in adipose tissue
 VIP (28AA peptide)
Actions
Potentate effects of Ach on salivary gland
Inhibit acid and pepsin secretion
Stimulates ventilation
Increases pancreatic and hepatic, intestinal
secretions
Causes vasodilatation
As a neurotransmitter
Neuroma – releasing VIP, is a cause of profuse
watery diarrhoea (pancreatic cholera)
 Ghrelin
Primarily secreted in stomach

Plays a central role in control of food intake

Stimulates GH secretion by acting directly on

receptors on the pituitary
Bombesin/
gastrin-releasing peptide (GRP)
27AA

Stimulated by oligopeptides

Stimulates acid and pancreatic secretion by

increasing gastrin and CCK release
 Peptide YY
Secreted by neuroendocrine cells of the ileum and colon
blood concentrations rising to peak levels 1 to 2 hours
after ingesting a meal
peak levels of PYY are influenced by the number of calories
ingested and the composition of the food,
higher levels of PYY observed after meals with a high fat
content.

Suppresses feeding
inhibits gastric acid secretion and motility
Increases water and electrolyte absorption in the colon
 Motilin
22 AA residues

secreted by enterochromaffin and Mo cells in the

stomach, SI, colon

Acts on G protein coupled receptors on enteric

nervous system to produce contraction of stomach
and intestines

Erythromycin binds to motilin receptors

Might have value in treating GI motility disorders
 Somatostatin
Secreted by D cells in the intestine and pancreas
14AAs/28AAs
Inhibits secretion of gastrin, VIP, GIP, secretin, motilin
Inhibition of gastrin secretion by acid (refer to gastrin
notes)
Inhibits pancreatic exocrine secretion, gastric acid
secretion, motility, GB contraction and absorption
 GIP (Glucose dependent
insulinotropic peptide)
Secreted by K cells in duodenal and jejunal mucosa
(43 aas)
Stimuli increasing release
Fat, glucose, AA, acid

Actions
Increase insulin secretion
Slow gastric emptying (gastro inhibitory pept)
Causes mesenteric vasodilatation
 Glucagon-like peptides
Are released from enteroendocrine cells in response to nutrient
ingestion

Two types of GLPs

glucagon-like peptide-1 (GLP-1)
glucagon-like peptide-2 (GLP-2)

GLP-1 and GLP-2 exhibit a diverse array of metabolic, proliferative

and cytoprotective actions with important clinical implications for
the treatment of diabetes and gastrointestinal disease, respectively

L cells that produce GLP-1 and GLP-2

the vagus nerve, the neurotransmitter gastrin-releasing peptide and the
hormone glucose-dependent insulinotropic peptide all contribute to the
rapid release of GLP-1 and GLP-2 from distal L-cells in response to
nutritional stimuli.
The actions of GLP-1 and GLP-2 are mediated via unique G
protein-coupled receptors.

The durations of their action are limited owing to a rapid

inactivation of these peptides by the ubiquitous protease dipeptidyl
peptidase-IV (DPP-IV)
the inhibition of DPP-IV activity or the development of DPP-IV-
resistant glucagon-like peptide analogues offers additional
therapeutic options for treating human disease.

GLP-1 and GLP-2 are secreted in a 1:1 ratio from intestinal L-cells
the majority of which are located in the distal ileum and colon
The half-life of active GLP-1 is less than 2 minutes22, GLP-2 is
approximately 5–7 minutes
GLP-1 and GLP-2 are co-encoded within the proglucagon gene,

is expressed in the a-cells of the endocrine pancreas, in the

enteroendocrine L-cells of the intestine and in the hypothalamus and
brainstem in the CNS

The major stimulus for GLP-1 and GLP-2 secretion is the ingestion
of nutrients, including glucose, fatty acids and dietary fibre.
Plasma levels increase 2–5-fold following food ingestion, the absolute
peak level being dependent on the size and nutrient composition of the
meal
When nutrients are ingested, the release of GLP-1 and GLP-2 into the
circulation occurs in a bi-phasic manner, consisting of a rapid (within
10–15 minutes) early phase followed by a more prolonged (30–60
minutes) second phase.
 Glucagon-like peptide-1
is an incretin hormone
Incretin amplifies secretion of insulin

GLP-1 enhances glucose-stimulated insulin secretion and

inhibits glucagon secretion, gastric emptying and feeding
has proliferative, neogenic and antiapoptotic effects on
pancreatic b-cells
GLP-1 and related analogues can reduce elevated fasting and
postprandial blood glucose levels in diabetic human subjects
recent studies illustrate a potential protective role for GLP-1
in the cardiovascular and central nervous systems.
Effects of GLP-1
 Incretin effect of GIP and GLP-1

Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose

levels. Incretins do so by causing an increase in the amount of insulin released from
pancreatic beta cells of the islets of Langerhans after eating, before blood glucose
levels become elevated(Tibaldi JM Adv Ther 2014)
 Overlap between Endocrine,
Neurocrine and Paracrine messengers
GIT Blood supply
 GIT blood flow
Blood vessels of the GIT are part of the Splanchnic
circulation
Includes blood flow through the gut itself through the
spleen, pancreas and liver
Blood flows from gut to the spleen and pancreas then flows
immediately into the liver by way of the portal vein

Supplied by
the celiac artery
Superior mesenteric artery
Inferior mesenteric artery
In liver, blood passes through millions of minute liver
sinusoids and finally leaves the liver via the hepatic veins
that empty into the vena cava of the general circulation

Parasympathetic stimulation of the stomach and lower

colon increases local blood flow that causes an increase in
secretion. (Secondary effect)

Sympathetic stimulation causes vasoconstriction reducing

blood flow
 Splanchnic circulation
Flow of blood through the
liver, before it empties into
the vena cava, allows the
reticuloendothelial cells
that line the liver sinusoids
to remove bacteria, alcohol
and other particulate
matter that might enter the
blood from the
gastrointestinal tract

The splanchnic circulation. (Redrawn with permission from Gelman S, Mushlin PS:
Catecholamine induced changes in the splanchnic circulation affecting systemic
hemodynamics. Anesthesiology 100:434–439, 2004.)
Nonfat , water-soluble nutrients
absorbed from the gut (such as
carbohydrates and proteins) are
transported in the portal venous blood to
the liver sinusoids

Both the reticuloendothelial cells and the

principal parenchymal cells of the liver,
the hepatic cells , absorb and store
temporarily from one half to three
quarters of the nutrient
Chemical intermediary processing of
these nutrients occurs in the liver cells

Almost all of the fats absorbed from the

intestinal tract are not carried in the portal
blood but instead are absorbed into the
intestinal lymphatics and then conducted
to the systemic circulating blood by way
of the thoracic duct , bypassing the liver.
 during active absorption of nutrients, blood flow in
the villi and adjacent regions of the submucosa is
increased as much as eightfold.

blood flow in the muscle layers of the intestinal wall

increases with increased motor activity in the gut

after a meal, the motor activity, secretory activity,

and absorptive activity all increase; likewise, the
blood flow increases greatly but then decreases back
to the resting level over another 2 to 4 hours.
Causes of increased blood
flow
Intrinsic factors
Locally produced vasoactive factors
Local reflexes
Local metabolic control

Extrinsic factors
Nervous Control of GIT Blood Flow
Possible Causes of the Increased
Blood Flow During GIT Activity
Although the precise cause or causes of the increased blood flow during increased gastrointestinal
activity are still unclear. The facts are known

Several vasodilator substances are released from the mucosa of the intestinal tract during the
digestive process. Most of these are peptide hormones, including cholecystokinin , vasoactive
intestinal peptide , gastrin , and secretin . These same hormones control specific motor and
secretory activities of the gut. (extrinsic factor)

Some of the gastrointestinal glands also release into the gut wall two kinins, kallidin and
bradykinin , at the same time that they secrete their secretions into the lumen. These kinins are
powerful vasodilators that are believed to cause much of the increased mucosal vasodilation that
occurs along with secretion. (Intrinsic)

Decreased oxygen concentration in the gut wall can increase intestinal blood flow at least 50 to
100 per cent; therefore, the increased mucosal and gut wall metabolic rate during gut activity
probably lowers the oxygen concentration enough to cause much of the vasodilation. The
decrease in oxygen can also lead to as much as a fourfold increase of adenosine , a well known
vasodilator that could be responsible for much of the increased flow. (Intrinsic)

1. The increased blood flow during increased gastrointestinal activity is probably a combination of
many of the aforementioned factors plus still others yet undiscovered.
Nervous Control of GIT Blood
Flow
Parasympathetic nerves going to the stomach and lower colon
increases local blood flow at the same time that it increases
glandular secretion
This increased flow probably results secondarily from the
increased glandular activity and not as a direct effect of the
nervous stimulation

Sympathetic stimulation has a direct effect on essentially all the

gastrointestinal tract to cause intense vasoconstriction of the
arterioles with greatly decreased blood flow.
After a few minutes of this vasoconstriction, the flow often
returns almost to normal by means of a mechanism called
“autoregulatory escape.” That is, the local metabolic
vasodilator mechanisms that are elicited by ischemia become
prepotent over the sympathetic vasoconstriction,
redilates the arterioles causing return of necessary nutrient blood
flow to the gastrointestinal glands and muscle.
Importance of Nervous Depression of
Gastrointestinal Blood Flow When Other
Parts of the Body Need Extra Blood Flow.
A major value of sympathetic vasoconstriction in the gut is that
it allows shut-off of gastrointestinal and other splanchnic blood
flow for short periods of time during heavy exercise, when
increased flow is needed by the skeletal muscle and heart.
Also, in circulatory shock, when all the body’s vital tissues are
in danger of cellular death for lack of blood flow—especially the
brain and the heart—sympathetic stimulation can decrease
splanchnic blood flow to very little for many hours.
In hemorrhagic shock or other states of low blood volume,
Sympathetic stimulation also causes strong vasoconstriction of
the large-volume intestinal and mesenteric veins can provide as
much as 200 to 400 milliliters of extra blood to sustain the
general circulation
 Splanchnic Circulation
Vasoconstrictors- Ang II, endothelin, Norepinephrine
(1 and -agonists), PGF2, Vasopressin (ADH)

Vasodilators- Ach, Adenosine, Bradykinin, GRP,

histamine, NO, VIP, 2-agonists

Vasorelaxation
cGMP
G-PR
dilator
Gs cAMP Decreased
free Ca++
AC

Vascular Smooth Muscle Cell

 Norepinephrine effect on
blood vessel smooth muscle

h
tt
 Control of food intake
Two control centres in the hypothalamus
Feeding centre (encourages eating behaviour)
Satiety centre (discourages eating behaviour)

Polypeptides affect food intake

Increase intake Decrease intake

Neuropeptide Y , CCK, leptin, insulin,
ghrelin,  endorphin, bombesin/GRP,
MCH (found in somatostatin,
hypothalamus), orexin neurotensin,
A,, CRH, MSH, oxytocin
 Definitions
Satiation signals the brain the meal is over.
occurs during a meal

Satiety is a physical feeling of fullness that allows us

to stop eating for a while.
satiety dwindles as nutrients diminish.
Regulation of food intake in the
hypothalamus
Ghrelin effect on the brain
Ghrelin effect on the brain

Trahurn and Bing 2006

 Phases of Gastrointestinal
Control
There are three phases
Cephalic
Gastric
Intestinal

Each phase is closely regulated by both local and

distant triggers
 Cephalic Phase
Initiated when receptors in the head are stimulated by
Sight
Smell
Taste
Chewing
Emotional/psychological state
Efferent pathways are mediated by parasympathetic fibers
in the vagus
Fibers activate neurons in the GI nerve plexuses, in turn
affect secretory and contractile activity.
Cephalic phase can be influenced by food preferences.
 Gastric phase
Initiated by
Distension
Change in pH
Amino acids
Peptides

Mediated by
short and long neural reflexes
Gastrin
 Intestinal Phase
Initiated by
Distension
Change in pH
Osmolarity
Various digestive products

Mediated by
Short and long reflexes
Secretin, CCK, and GIP
Phases of Gastrointestinal Control

http://biomedicool.com/post/160492332617/regulation-of-digestion
Secretions and digestion
 Secretion – General
Properties
Tightly regulated processes (receptors)

In the case of protein digesting enzymes, they are

usually released in their pro-enzyme or zymogen form

Secretions are involved in both the maintenance and

integrity of the inner surface of the GI tract (Cl-,
mucus, HCO3-, etc) in addition to digestive processes
Digestion and Absorption -
General Concepts
Digestion is the process of breaking down food into
an absorbable form
Some digestion occurs in the mouth and stomach but
most of the final digestion occurs in the intestinal
lumen or at the surface of the absorptive cells
(enterocytes)
Absorption is the process by which molecules of food
are transported across the enterocyte membrane
(transcellular/cellular) or between cells (paracellular)
and into the blood or lymph
Mouth (salivary glands), pharynx
and oesophagus
 Mouth
Where digestion starts.
Chewing
Mechanical processing
Through actions of teeth, tongue, and palatal surfaces

Saliva secreted by three pairs of salivary glands loacted in

head, (parotid, submandibular and sublingual) drains into
the mouth through short ducts
There are 600 other minor glands in the oral cavity and Von
Ebner's Glands found in circumvallate papillae of the tongue

Saliva contains mucus, moistens

Hypothalamic centres increase or decrease salivation
https://training.seer.cancer.gov/anatomy/digestive/regions/mouth.html
Tongue

Muscular organ
Manipulates food
for mastication
Takes part in
swallowing
Enables speech
Taste receptors:
sweet, sour, salty,
bitter, savoury
(umami)
 Tongue and taste buds

Ganong (Smell and Taste)

fungiform papilla has up to five taste buds
mostly located at the top of the papilla,

Vallate and foliate papilla contain up to 100 taste

buds,
mostly located along the sides of the papillae.
151
Main Salivary Glands
1. Parotid gland
2. Submandibular gland
3. Sublingual gland

Secretions of the three

glands differ in their
relative proportion of
proteinaceous and
mucinous components,
Salivary Gland
Formed by passive filtration
The acinus is very permeable to water and
acts in filtering water and ionic components
from blood
Salivary enzymes secreted from the acinar
cells

Salivary glands are richly endowed with

surrounding blood vessels that dilate when
salivary secretion is initiated
Secretion rate is dependent on blood flow

ductal cells are very impermeable to water

Reabsorption of electrolytes
No concurrent movement of water.
 Mouth contd
 Human saliva is composed
 mostly of water (99.5%),
 Electrolytes (low in Na+ and Cl-, high in K+ and HCO3-)
 Mucins, glycoproteins,
 antibacterial compounds, (IgA, lactoferrin, lactoperoxidase, lysozymes)
 Proline rich proteins that protect tooth enamel by binding calcium and bind
tannins
 Histatins – prevent fungal infections
 Salivary amylase (secreted by salivary glands), lingual lipase (secreted by
glands in the tongue) and various other enzymes

 1000 to 1500 ml secreted per day

 pH of 6.5-7.5
 Functions of Saliva
• Digestion - amylase & lingual lipase
• Lubrication - chewing, swallowing & speech
 Mucins, and glycoproteins

• Protection
– Against hot fluids - increased production
– Against gastric acid if vomit
– Against bacteria - lysozyme & lactoferrin & immunoglobulins
– Keeps mouth and teeth clean by dissolving and washing food
particles from between the teeth
• Taste – dissolves food particles and carries food particles to
taste buds

156
Proline rich proteins protect tooth enamel by binding
calcium and by binding toxic tannins
Binds water giving a protective layer to reduce dental
caries
Also binds bacteria in the presence of mucins, which
unfortunately increases plaque formation an ultimately
tooth decay

Proline- rich proteins from the parotid saliva have

been found to increase binding of anthocyanin and
black tea polyphenols to hydroxyapatite,
Functions of constituents of
saliva
Secretion of saliva
o Hypotonic in relation to plasma
• In acini it is isotonic
• Since the ductal cells are relatively
impermeable to water, the loss of NaCl
renders the saliva hypotonic
 Potassium level 2x to 30x higher than plasma
• Aldosterone increases potassium concentration
and decreases sodium concentration in saliva
• Salivary secretions are regulated almost entirely by nervous
mechanisms
Parasympathetic stimulation, produces flow of watery saliva that
is rich in enzymes.
Sympathetic stimulation produces a much smaller volume of 159
thick saliva that is rich in mucus.
 Parasympathetic regulation of
saliva secretion

Ganong 2016
Salivary secretions are also prompted by nausea,

But inhibited by fear or restful during sleep.

Salivary flow peaks in the afternoon

Decreases at night
 Regulation of Salivary secretion

A) Simple or unconditioned: The presence of food in the

mouth results in reflex secretion of saliva.
Stimulus: presence of food in the mouth.
Receptors: taste buds, pressure receptors .
Afferent: nerves from taste buds carry impulses to
salivary centre. Centre: salivary centre in medulla
oblongata (in brain stem).
Efferent: autonomic nerves supplying salivary
glands.
1.5ml – 2 ml per minute
Less than 0.7 ml per minute is hyposalivation
163
Fejerskov & Kidd, 2003, p. 11) (Fig 2.3 Reflex arch of Salivary Secretion))
B) Conditioned

• An acquired reflex and needs training

• Eg Bell to indicate meal time (Pavlov’s Theory).
• The centre is in the cerebral cortex.
• The sight, smell, thought of food in the
absence of food in the mouth increase
salivary secretion.
165
166
 Chewing/Mastication
Caused by the somatic nerves to the skeletal muscles
of the mouth and jaw (voluntary)
Innervated by the
mandibular brunch of the trigeminal nerve
Motor branch of the fifth cranial nerve
Controlled by nuclei in the brainstem (also controls swallowing)

Includes reflex rhythmic chewing motions, activated

by the pressure of food against the gums, hard palate
at the roof of the mouth, and tongue
Activation of mechanoreceptors leads to reflex inhibition of
the muscles holding the jaw closed
The resulting relaxation of the jaw reduces the pressure on
the various mechanoreceptors, leading to a new cycle of
contraction and relaxation
All the jaw muscles working together can close teeth
with a force as great as 25 kgs on the incisors and 90
kgs on the molars!

Edentulous patients (patients with no teeth) are

generally restricted to a soft diet and have
considerable difficulty eating dry food.
 Chewing
Chewing prolongs pleasure of food.

Chewing reduces risk of choking from large food particles that may
lodge over the trachea.

Particles that are small tend to disperse in the absence of saliva and
also make swallowing difficult because they do not form a bolus

The number of chews that is optimal depends on the food, but usually
ranges from 20 to 25

Symptoms of choking similar to a heart attack.

Heimlich maneuver can be used to dislodge obstructing particles

from the airways.
 Oesophagus
A hollow muscular tube

About 25 cm (10 in.) long and 2 cm

(0.80 in.) wide

Conveys solid food and liquids to the

stomach
4cm/s

Begins posterior to cricoid cartilage

is a reflex response that is triggered

by afferent impulses in the trigeminal,
glossopharyngeal, and vagus nerves
Chewing and swallowing
Swallowing phases
 Deglutition innervation
• Trigeminal nerve (V),
• Glossopharyngeal nerve (IX),
• vagus nerve (X)
• Hypoglossal nerve (XII)

ttp://www.biologydiscussion.com/human-physiology/digestive-system/3-important-stages-of-swallowing-digestive-system/6253
 Manometry
Oesophageal manometry is used to identify problems
with movement and pressure in the oesphagus that
may lead to problems like gastroesophageal reflux
disease (GERD/GORD/heartburn)
Why do manometry
Manometry demonstration
 Mechanism of Swallowing
3 stages:
Oral or Voluntary: bolus of food is passed into the
pharynx by upward and backward movement of
tongue against palate. This stimulates the touch
receptors that initiate the swallowing reflex.
Pharyngeal: involuntary passage of bolus through the
pharynx into oesophagus. Respiratory passageways
are closed & respiration is inhibited (protective
reflexes).
Oesophageal: involuntary passage of bolus from
esophagus to stomach by peristaltic movements of
esophagus. 177
No digestion or absorption

Secretions: mucus

Swallowing or deglutition takes place

is the process of moving food from the mouth through
the esophagus into the stomach
Protective reflexes during pharyngeal phase of swallowing:

a) Elevation of the soft palate: closes posterior nasal

openings, thus preventing food reflux into the nasal
cavities.
b) Elevation of the larynx against the epiglottis: closes
the superior laryngeal orifice (glottis), thus preventing
food entrance into the trachea.
c) Approximation of the vocal cords: This also closes
the glottis, but its role is much more important than
that of the epiglottis.
d) Temporary apnea: stoppage of breathing for few
seconds which also prevents food entrance into the 179
trachea.
Other events during swallowing

180
Swallowing-Oesophageal
Phase
Uses peristalsis to propel food towards the stomach.
initiated by stretching of gut wall & occurs in all gut
regions from esophagus to rectum.

1 peristaltic wave takes about 9 seconds

If a large particle does not reach the stomach in the
first contraction a second wave occurs due to the
distension caused by the food particle lodged in the
oesphagus
The major transmitters in the peristaltic reflex are:
acetylcholine (ACh) and substance P (SubP) are the
predominant excitatory neurotransmitters,
vasoactive intestinal polypeptide (VIP) and nitric oxide
are the predominant inhibitory neurotransmitters.
183
 LES
Made up of
The esophageal smooth muscle
Diaphragm
Sling fibers of the stomach wall
Assessing pressure changes in the
oesophagus
We use manometry to assess the pressure changes evoked
by the contractions in the oesophagus muscular portion
Normal range – 30 -180mmHg
Lower esophageal sphincter pressure- 10 to 45 mmHg
15–25 mm Hg above gastric pressure
Can be used to estimate pleural pressure in the respiratory
system
Therefore varies when one is expiring and inspiring as the
intrapleural pressures change
Total pressure applied to respiratory system must overcome
the opposing forces of elasticity and resistive properties of
the respiratory system
 Antireflux mechanisms
Normally there is positive pressure gradients between
the abdomen and the thorax that tends to promote the
reflux of material form stomach to oesophagus
Antireflux mechanism prevents this

LES maintains a resting pressure of 10-45 mmHg

higher than that of the stomach

Normally LES relaxes 3-10 seconds to allow

swallowed bolus to enter the stomach
Long than that risk of reflux increased
Diaphragm and oesophagal
activity
Diaphragm divided into two
Crural
Costal

Crural muscle (extrinsic

sphincter)surrounds the esophagus
Fibres of the exert a sphincter-like
action on the esophagus..
Innervation supplied by the phrenic

The oblique or sling fibers of the

stomach wall create a flap valve that
helps close off the esophagogastric
junction and prevent regurgitation when
intragastric pressure rises.

Has a role in the esophagogastric

junction (EGJ) or gastroesophageal
junction physiology

GI Motility online (May 2006) | doi:10.1038/gimo14

 EGJ junction physiology
Under resting conditions and at end expiration, the EGJ
pressure mostly comes from smooth muscle LES
increase with each inspiration is related to the crural
diaphragm contraction

Amplitude of EGJ pressure related to inspiration is directly

related to the depth of inspiration
With maximal inspiration, the EGJ pressure increases from
20 mm Hg to more than 100 mm Hg
Crural diaphragm provides tonic or sustained increase in
the EGJ pressure during periods of abdominal
compression, straight leg raise, and valsalva maneuver.
 Inspiration and the LES
relationship
During inspiration the diaphragm contracts, flattening and
increasing the negative pressure in the lungs to facilitate
inhalation of air
Coordinated by the inspiratory nerves from the brainstem
During inspiration crural diaphragm contracts, pinching the
distal oesophagus, keeping it closed
Crural muscle does not contract during oesophageal distension
(swallowing) so as to facilitate entry of food into the stomach
from the oesophagus
selective inhibition of crural fibres could be due to a reflex pathway
caudal to the central respiratory pattern generator in the medulla,
nitric oxide from enteric neurons could be blocking
neurotransmission across the skeletal neuromuscular junction
Transient lower esophageal
sphincter relaxation
Transient lower esophageal sphincter relaxation
(TLESR) is defined as lower esophageal sphincter
relaxation that is induced spontaneously without
swallowing

Occurs in patients with gastroesophageal reflux

disease (GERD) and in controls
 Inhibitors of the TLESR
GABA b agonist

Atropine

CCK-A receptor antagonist

Morphine (mu receptor agonist)

Nitric oxide antagonist,

Metabotropic glutamate receptor

subtype 5 (mGluR5) antagonists

Cannabinoid receptor (CBR1) agonist

All of these agents reduce the frequency

of TLESR
spontaneous swallows but do not
completely block them
 Manometry
Oesophageal manometry is
a procedure to identify
problems with movement
and pressure in the
oesophagus that may lead to
problems like gastro-
oesphageal reflux
(GORD/GERD/heartburn)

Normally muscles contract

in an orderly sequence
through the process of
persiatlsis.
http://medcaretips.com/esophageal-manometry/
 High resolution oesophageal
manometry pressure topography
plot example

Clarke and Hirano Upper Gastrointestinal Tract January. Scleroderma 2012

 High resolution oesophageal
manometry pressure topography
plot example notes
The left panel depicts a normal swallow with
relaxation of the upper esophageal sphincter,
sequential (peristaltic) contractions in the esophageal
body and relaxation of the lower esophageal
sphincter. The right panel from a patient with
scleroderma demonstrates intact function of the upper
esophageal sphincter and proximal esophagus but
complete absence of contractile activity in the
esophageal body (aperistalsis) and lower esophageal
sphincter (lower esophageal sphincter hypotension)
Aerophagia & Intestinal Gas
Some air is unavoidably 200 mL swallowed air +
swallowed in the process 500 mL-1500mL locally
of eating and drinking produced
(aerophagia).
gas in the intestines
regurgitated (belching), causes cramps
Some gases are borborygmi (rumbling
absorbed, noises) and abdominal
Much passes on to the discomfort
colon
Bacterial gas products
+ aerophagia=flatus
 Achalasia
Is a condition in which food accumulates in the esophagus and the
organ becomes massively dilated.

Caused by increased resting LES tone and incomplete relaxation on

swallowing due to damage to or malfunction of the enteric nerves in
the LES wall.

Can be treated by pneumonic dilation of the sphincter or incision of

the esophageal muscle (myotomy).

The opposite condition is LES incompetence, which permits reflux

of acidic gastric contents into the esophagus (GERD;
gastroesophageal reflux disease).
This common condition causes heartburn and esophagitis and can lead
to ulceration and stricture of the esophagus due to scarring.
Can be treated by inhibiting acid secretion with H2 receptor blockers or
omeprazole (a proton pump inhibitor)
Stomach
 Stomach
Saclike organ located between the
oesophagus and small intestine
Stores, dissolves and partially digests
macromolecules in food
Regulates the rate at which the contents of
the stomach empty into the small intestine
glands lining the stomach wall secrete a
strong acid( HCL) and several precursor
protein-digesting enzymes (pepsinogen)
Stomach layers- an expanded J-shaped
segment of the GIT
Resting volume Receptive relaxtion is
approximately 500 ml produces a pressure change of
10-20 cmH2O (7.3-
 intragastric
pressure normally 5- 14.7mmHg)
10mmHg Due to vago-vagal reflex
LES resting pressure of When food enters the stomach a
"vagovagal" reflex goes from the
10-45 mmHg stomach to the brain, and then back
again to the stomach causing active
Maximum volume relaxation of the smooth muscle in
approximately 2000-4000 the stomach wall

ml

199
The four regions of the
stomach
 1. Cardia – is the region of the
stomach immediately surrounding
the junction of the esophagus with
the stomach. 

2. Fundus – is the region of the

stomach superior to the
gastroesophageal junction. 

3. Body – is the largest region of the

stomach and lies between the fundus
and the lower curving segment of the
J. 

4. Pylorus – is the curve of the J. A

muscular pyloric sphincter regulates
the release of chyme into the
duodenum.
Recent evidence suggests that vasoactive intestinal
peptide (VIP) and nitric oxide (NO) rather than
acetylcholine (ACh) are the transmitters that signal
receptive relaxation to occur

They also appear to be the transmitters that signal

certain sphincters to relax

Parasympathetic nerve supply comes from the vagi

Sympathetic supply comes from the celiac plexus.

Hormones affecting the
stomach
Cells in Gastric Mucosa
Stomach enzymes
Gastric Pits
Gastric pit cells are
renewed every 2-4 days

The high rate of turnover

is a protective mechanism
protects the epithelial
lining of the stomach
from
the proteolytic action
of pepsin
the acid produced by
parietal cells
Ganong 2016
Gastric mucosa protection
Regulation of secretions in the
Stomach
Neural, hormonal, and paracrine
pathways directly regulating
parietal cell acid (H+) secretion.

https://clinicalgate.com/gastric-secretion/
Parietal cell structure
Acid Regulation in the
Stomach

GRP
Stimulation of stomach
secretions
HCL production
https://doctorlib.info/physiology/medical/222.html
Ganong 2016
Pepsinogen secretion
Activation of pepsinogen
Pepsinogen=MW 42 500

Pepsin=MW 35 000

Vander et al 2001
Pepsin will digest up to 20% of ingested amide bonds by
cleaving preferentially at the N-terminal side of aromatic
amino acids such as phenylalanine, tryptophan, and
tyrosine.
Small amounts of pepsin pass from the stomach into the
bloodstream
Activity in plasma limited because optimum pH for activity
is acidic environment.
Plasma pH is 7.35 - 7.45
Pathological states like Zollinger Eddison Disease and
stomach ulcers, high plasma pepsin
 Intrinsic Factor & Vit B12
Absorption
Dietary proteins contain Vitamin B12 (cobalamin)

B12 binds salivary R protein in stomach

Pancreatic proteases remove R protein in duodenum

Intrinsic Factor from stomach then binds B12 in

duodenum

Intrinsic Factor/B12 complex binds to receptor in

terminal ileum for absorption
 Bicarbonate production and
respiratory quotient
Stomach has negative respiratory
quotient (higher arterial CO2 in the
arterial blood than in venous)

Post prandial alkaline tide

a condition, normally
encountered after eating a meal,
where during the production of
HCl by parietal cells in the
stomach, the parietal cells
secrete bicarbonate ions across
their basolateral membranes and
into the blood, causing a
temporary increase in pH.

The liver and pancreas buffer

excess acid from the stomach

They secrete the excess bicarbonate

into their lumens
Mixing of stomach contents

0.5 ml passes through pyloric sphincter

per contraction through a 2mm diameter passage
 Gastric emptying
Depends on type of food ingested.
1-4 hours

Carbohydrate rich food leave stomach in

a few hours

Protein-rich food leaves more slowly

Fat-rich food takes the longest time to

leave the stomach

Hypertonic or acidic content has slower

gastric emptying rate
Enterogastric reflex regulates emptying
Receptors in duodenum
Neuronal and hormonal control
Optimises delivery rate for digestion and
absorption
 Pathophysiology of the
stomach
Reflux of gastric contents into the esophagus caused
by chronic vomiting or an incompetent lower
esophageal sphincter can lead to “esophageal
gastritis”
TLERS

Unregulated dumping of gastric contents into the

small intestine causes duodenal ulcerations
Peptic Ulcer Disease – Risk
Factors
NSAID and chronic alcohol use – 15-25% of ulcers
Ethanol is lipid soluble and diffuses into epithelial cells
where it interferes with cell metabolism, decreasing mucus
production and increasing cell permeability
aspirin may act primarily through inhibition of ecosinoid
metabolism.

Tumors (Zollinger Ellison Syndrome)

The gastrinomas produce large quantities of gastrin
resulting HCl release. Causes severe ulceration in the
stomach and duodenum.

Helicobacter pylori- 75-85% of ulcers

 Mucosal Defenses in the
Stomach
Mucus Layer and Alkaline Layer
at Surface (surface mucus cells)

Tight junctions between cells

Rapid cell turnover

Prostaglandins (increase mucus

production)

Trefoil peptides, synthesised and

secreted by goblet cells
Provide protective layer

Low luminal pH inhibits

bacterial growth
Trefoil Peptides
Has healing properties

Considered as Rapid
Response agents to
mucosal injury; with up-
regulation of expression
in the early stages of
mucosal repair.
Pancreas Liver and Small Intestine
Pancreas
 Pancreas
Has two portions
Endocrine
Exocrine

Endocrine function
Secretion of insulin (-cells) ,
Secretion of glucagon (-cells),
Secretion of somatostatin(-cells)
Pancreatic exocrine function
Secretes a bicarbonate and a number of enzyme
(pancreatic juice)
Enzymes secreted by gland cells at the pancreatic
end of the duct system
Bicarbonate ions secreted by the epithelial cells
lining the ducts
Bicarbonate and enzymes secreted into ducts that
converge into the pancreatic duct (1500 ml/day)
Duct joins the common bile duct from the liver
just before it joins duodenum
 Composition of pancreatic
juices

Volume of secretions is 1500ml

Structure of the pancreas

Thomas 2008
 Control of pancreatic
secretions

adapted from https://basicmedicalkey.com/the-exocrine-pancreas/

Thomas 2008

Jaster 2004
 Ion transport pathways in the
pancreatic duct cells

Ganong 2016
 Pancreatic enzymes
Granules which contain the enzymes called Zymogens

Enzymes that digest protein are secreted as inactive

proenzymes

All other enzyme are secreted as active enzymes

Activation of pancreatic proteases
 The Liver
Cells in the liver
Hepatocytes,
Hepatocytes make up about 80% of the cells in the liver.
store glucose in the form of glycogen , also vitamin B12, folic acid and
iron
participate in the turnover and transport of lipids.
synthesize some of the plasma proteins (albumin, α and β globulins,
prothrombin, fibrinogen
metabolize/detoxify fat
Kupffer,
Specialized macrophages
Ito
Hepatic stellate fat storing cells, produce fibroblast growth factors
Thought to be involved in regeneration (embryogenesis, angiogenesis,
wound healing, and endocrine functions)
Activated ito cells secrete collagen scar tissue, which can lead to cirrhosis.
pit cells-liver-specific natural killer (NK) cells
contain specific granules, large granular lymphocytes
 The Liver (cont.)
25% of cardiac output (1/3 arterial – supplying 25 –
50% of oxygen)

Wide range of functions with incredible functional

reserve, hence hypoglycaemia is rare in liver disease

Has a great regenerative capacity

Insulin and glucagon involved in regeneration
 Functions
Synthesis of proteins (albumin, acute phase
reactants, clotting factors)
Bile excretion
Disposal of cholesterol, synthesis of bile acids
Metabolism of glucose, fats, drugs, etc
Storage of nutrients
Metabolism of hormones (insulin, glucagon, cortisol,
GH, thyroxine
Immunological function
 Immunological function
Phagocytosis

Cytokines

Metabolites of AA

Antigen presentation

IgA
 Bilirubin Metabolism
Most bilirubin is formed in tissues in tissues by
breakdown of hemoglobin
Bilirubin is bound to albumin in the circulation
This complex, although tightly associated, can
dissociate in liver, bilirubin binds cytoplasmic
proteins (Y and P)
It is then conjugated to glucuronic acid (2 molecules
of UDP GA) by UDP glucuronsyl transferase
The glucuronide is water soluble and is secreted by
liver
 Jaundice
Is evident when bilirubin is greater than
34micromol/l

Can be due to pre, hepatic and post hepatic

mechanisms

Bilirubin as a lab test, shows obstruction of bile

secretion

In obstruction ALP and Lipoprotein X increase in

plasma
 Bile
Made up of bile salts, pigments dissolved in an
alkaline solution
Abt 500ml secreted per day
Bile acids synthesised from cholesterol at rate of 0.2
– 0.4g/d
They are conjugated glycine/taurine - derivative of
cysteine
Primary bile acids are cholic and chenodeoxycholic
acids
 Functions
Facilitate action of
Lipase
Phospholipase A (pro-phospholipase A )
2 2

Cholesteryl ester hydrolase

Emulsification of fat
Absorption of fat
There is an enterohepatic circulation, 90 – 95% absorbed in
small intestine using a sodium dependent co – transporter
5 – 10% are converted to secondary bile acids (deoxycholate
and lithocholate)
Deoxycholate is wholly absorbed
Implicated in pathogenesis of some GI disorders
 Bile salts
primary bile acids
cholic acid and
chenodeoxycholic acid in
humans

secondary bile acids (bacteria +

cholic acid in the colon)
deoxycholic acid, lithocholic
acid and ursodeoxycholic
acid

Approximately 600 mg of bile

salts are synthesized daily

bile acids + glycine or taurine =

bile salts (conjugated bile acids)
Reabsorption of conjugated
and unconjugated bile acids
 Gall bladder
• No digestive role.
• Stores bile.
The gall bladder can hold up to 4 grams of bile

• Concentrates bile.
• Empties during meals.
• Secretes mucus.
 Gall Bladder regulation
Substances that cause contraction of the gall bladder
are called cholagogues
CCK

Substances that cause secretions from the gall bladder

are choleretics
Secretin
Vagal stimuli
Regulation of bile secretion and
gall bladder emptying
• Hormonal:
– Secretin: secreted in response to acid chyme, causes secretion
of bile rich in water and HCO3-
– CCK: secreted in response to fatty acids in duodenum, causes
gall bladder to contract and sphincter of Oddi to relax.

Neural
Vagal stimulation:
Increases bile secretion
Weak contraction of gall bladder
Hormones affecting the liver
Hormones affecting the
gallbladder
Hormones affecting the sphincter
of Oddi
 Gallstones
Usually Calcium bilirubinate, or cholesterol
3 factors important in formation of gallstones
Bile stasis
Supersaturation of bile in cholesterol (cholesterol
insoluble, kept in solution by bile salts so above a
critical conc cholesterol crystallises
Nucleation (?glycoproteins eg Glycoprotein 2)
factors favour formation of gallstones
Small intestine activity
 Small Intestine
Tube is approximately 5-6 m in length leading from the
stomach to large intestine.

divided into 3 segments

duodenum- initial segment (25 cm)
jejunum- middle segement (1.9m)
ileum - longest segment (2.85m)

Site of final stages of digestion

site of absorption
 Digestion
Hydrolytic enzymes breakdown molecules of
intact or partially digested
carbohydrate(CHO), fats and proteins to
monosaccharides, fatty acids (FA) and amino
acids(AA) respectively.
Some enzymes are on the luminal surface of
the intestinal lining cells, while others are
secreted by the pancreas and enter the
intestinal lumen.
 Digestive Enzymes
Enzymes secreted by glandular
cells

Glandular cells store enzymes in

vesicles until needed

Protein synthesis mechanism

used to make enzymes

From ribosome to RER to Golgi

body to the secretory vesicles
takes 20 mins

Innervation through ligands

stimulate secretion
Plicae Circulares: Increased Absorptive Area

Copyright 1997-8 Novartis. All rights reserved.

 Absorption layer

https://www.atsu.edu/faculty/chamberlain/website/lectures/tritzid/GASTRO.htm
Extracellular matrix of the enterocyte brush
border with its glycocalyx (contains enzymes)

Glycocalyx
 Absorption surface of the small
intestine
Unstirred layer of composed
of
Mucous
thin film of water and
bicarbonate

Constant contact with the

brush border of the secreting
and absorbing mucosal
surface

products of digestion must

penetrate before being
absorbed

https://en.wikibooks.org/wiki/Medical_Physiology/Gastrointestinal_Physiology/Digestion_%26_Absorption
 Duodenum
Receive juices from pancreas, liver
and its own wall
Secretion from the duodenum: They
finish off the last step of digestion.
Peptidases (or dipeptidases) break
off the bond between dipeptides to
free 2 amino acids
Disaccharidase (maltase, sucrase,
lactase) break off disaccharides into 2
monosaccharides (mostly glucose) Figure 20.4

Intestinal lipase breaks off

diglycerides into monoglycerides and
fatty acids.

Nutrients are completely degraded into

forms that can be absorbed by cell (step 2
of chemical digestion)
 Absorption

Absorption occurs across the epithelial cells

and enters the blood and/or lymph.
Vitamins (vit), minerals and water, which may
not require enzymatic digestion, are also
absorbed in the small intestine.
Jejunum-Ileum

Nutrients will be reabsorbed

along the jejunum-ileum
They need to penetrate
unstirred layer

Brush border contains villi

which increase the surface
of absorption

The villi are structured for

nutrient absorption
 Absorption in the small
intestine.
Absorption of monosaccharides and amino
acids
by specific transporter-mediated processes in the plasma
membranes of the intestinal epithelial cells
Mainly secondary active transport
Facilitated for fructose

Absorption of FA
diffusion

Absorption of minerals
active transport

Absorption of water
osmosis
Ganong 2012
Protein digestion in small
intestine
Activation of pancreatic proteases
 Protein digesting intestinal
mucosa enzymes

(Enterokinase)
Sites acted on by the
peptidases
Enzymes for Protein Digestion
Peptide Absorption and further
digestion
Peptide Absorption and further digestion

At least 5 transport systems on basolateral side

Protein digestion, peptide and
Amino acid absorption
summary
 Carbohydrates
Class Examples Made of
Polysaccharides Starch Glucose
Cellulose Glucose
Glycogen Glucose
Disaccharides Sucrose Glucose + fructose
Lactose Glucose + galactose
Maltose Glucose + glucose
Monosaccharides Glucose
Fructose
Galactose
Carbohydrate digesting intestinal enzymes
Carbohydrate Digestion: Breakdown to
monosaccharide, which can be absorbed

Thomas 2008
Figure 21-14
 Absorption of
monosaccharides
Fructose -facilitated diffusion
Glucose -secondary transport coupled
to sodium
Galactose -secondary transport coupled
to sodium
The monosaccharides enter blood stream from
epithelial cells by facilitated diffusion transporters
 Carbohydrate Absorption in the Small
Intestine

http://www.austincc.edu/apreview/EmphasisItems/Glucose_regulation.html
Fat digestion and absorption
Fats digestion occurs mostly in the small intestine

Enzymes involved
Pancreatic lipase and colipase
Cholesterol esterase
Phospholipase A2 enzyme

Fats are hydrophobic

Digestion of lipid droplet occurs only at the surface of droplet

Rate of digestion  by division of the large droplets into a number

of small droplets, diameter of 1mm, thereby increasing surface
area. (emulsification)
 Digestion and Absorption
The role of bile salts in emulsions and micelles

Figure 21-20
Fat digestion and absorption
Digestive enzyme -pancreatic lipase
Pancreatic lipase catalyzes split of bonds linking fatty
acids to first and third carbon atoms of glycerol
Coating of droplets with emulsifying agents impairs
lipase accessibilty to droplet
Colipase, binds to the –COOH-terminal domain of the
pancreatic lipase, and opens the active site
Activated by trypsin
Aids the binding of lipase to the fat droplet
 Digestion and Absorption
Triglycerides digested into monoglycerides and free fatty
acids

Figure 21-18
 Cholesterol esterase
Secreted by pancreas

Activated by bile salts

Cholesteryl esters + H20 Cholesterol + FA

Catalyzes the hydrolysis of

cholesterol esters,
esters of fat-soluble vitamins,
phospholipids,
triglycerides
 Phospholipase A2
Activated as proenzyme (zymogen)
Activated by trypsin
Hydrolyzes phospholipids and hepatobiliary
phosphotidylcholine
Splits a fatty acid off phosphatidylcholine (PC), forming lyso-
PC.
Phosphatidylcholine + H20 lysophosphatydycholine + FA
Lyso-PC damages cell membranes.
Acute pancreatitis, a severe and sometimes fatal disease,
may occur when phospholipase A2 is activated prematurely in the
pancreatic ducts
formation of lyso-PC from the PC that is a normal constituent of bile causes
disruption of pancreatic tissue and necrosis of surrounding fat.
Digestion and Absorption of
Fats Large fat droplets
from stomach
Bile salts
from liver 1 Bile salts from liver coat
1
fat droplets.

Emulsion 2 Pancreatic lipase + colipase,

phospolipase A2 and cholesterol
Lipase + colipse, Bile salts
Phospolipase A2 esterase break down fats into
2 recycled
Cholesterol esterase respective products and fatty
Micelles acids stored in micelles.
Lumen of
small intestine
3b
3a 3a Monoglycerides and
fatty acids move out of
micelles and enter cells
by diffusion.
Smooth
ER
3b Cholesterol is
4 Triglycerides + cholesterol + phospholipids transported into cells
Cells of Chylomicron by a membrane
small transporter.
intestine Golgi
apparatus
4 Absorbed fats combine
with cholesterol, phospholipids
and fat soluble vitamins
5 in the intestinal cells to form
Interstitial chylomicrons.
fluid
Capillary
Lacteal
5 Chylomicrons are
Lymph
to released into the
vena lymphatic system.
cava
Figure 21-19
Short-chain Fatty Acids
Produced in the colon and absorbed from it

2–5-carbon weak acids formed by the action of colonic bacteria

complex carbohydrates, resistant starches, and other components of the
dietary fiber,

Average normal concentration of about 80 mmol/L in the lumen (70-

140 mmol/L depending on diet).
95% absorbed colonic epithelial cells

Forms of Short chain fatty acids

About 60% is acetate,
25% propionate
15% butyrate.
Purpose of Short chain fatty
acids
absorbed by specific transporters present in colonic
epithelial cells
in part by exchange for H+,
Linked to Na absorption (Na-SCFA)

metabolized and make a significant contribution to the total

caloric intake

exert a trophic effect on the colonic epithelial cells and

combat inflammation

Helps to maintain acid base equilibrium (exchange for H+)

Benefits of SCFA
Digestion of Nucleic Acids
Enzymes
Pancreatic ribonuclease and deoxyribonuclease 
nucleotide monomers
Brush border enzyme nucleosidases and phosphatases
 free bases, pentose sugars, phosphate ions
digested into nitrogenous bases and monosaccharides
Nucleic Acid digestion and
absorption summary
 Digestion and Absorption of
Micronutrients
Intestine absorbs vitamins and minerals
Fat-soluble vitamins (A, D, E, K) absorbed with fats in small
intestines
Those with esters are predigested by cholesterol esterase from the
pancreas to release the fat soluble vitamin

Water-soluble vitamins (C, B vitamins) absorbed by mediated

transport
Exception: Vitamin B12 when complexed to intrinsic factor,
secreted in the stomach, and absorbed in ileum by endocytosis
In high concentration (as in supplements), water soluble vitamins
can be absorbed by diffusion or passive transport.
Minerals absorbed by active transport
 Fat soluble viatmins
Retinol (vitamin A)is found typically bound to fatty
acid esters (most common retinyl palmitate).
Retinyl esters and beta-carotene are often bound to
protein in food from which they must be released.
Esters removed from vitamin by cholesterol esterase
Tocopherols (vitamin E) are found free in foods;
tocotrienols are often esterified, requiring pancreatic
esterase and/or duodenal mucosal esterase that
function at the brush border of the intestine to
hydrolyze tocotrienols for absorption.
 Schematic depiction of the membrane expression of well-characterized water-soluble vitamin
transporters in polarized intestinal epithelial cells by sodium coupled transporters .

Hamid M. Said Biochem. J. 2011;437:357-372

©2011 by Portland Press Ltd

 Water soluble vitamins
Thiamine
In plants, thiamin exists in its free form. In animal
foods, > 95% occurs in a phosphorylated form
(primarily as Thiamin Diphosphate (TDP) and Thiamin
Triphosphate (TTP)).
Intestinal phosphatases and pyrophosphatases remove
the phosphate prior to absorption.
Absorption (free thiamin, not phosphorylated thiamin)
can be both active and passive, depending on the
amount present in the intestine
 Riboflavin
The form of riboflavin in food varies.
Free riboflavin
protein-bound riboflavin.
Flavin Mononucleotide (FMN) or Flavin Adenine
Dinucelotide (FAD).

Need to remove protein and phosphate (phosphatases)

to absorb.

Riboflavin attached to protein is freed by the action of

HCL and gastric and intestinal enzymes.
 Niacin Vitamin B3
Nicotinamide Adenine Dinucelotide (NAD) and
Nictinamide Adenine Dinucleotide Phosphate
(NADP) may be hydrolyzed within the intestinal tract
by glycohydrolase to free nicotinamide.

Nicotinaminde and nicotinic acid are absorbed using a

a sodium-dependent, saturable process.

In the intestinal cell, nicotinic acid is believed to be

converted into nicotinamide.
 Pyridoxine
For absorption, the phosphorylated forms need to be
dephosphorylated.

Alkaline phosphatase found at the brush border of

the intestine hydrolyze the phosphate toyield either
Pyridoxine,
Pyridoxal
Pyridoxamine .

Absorbed by passive diffusion in jejunum

 Folate
Natural folate is in bound form which is combined
with a string of amino acids known as polyglutamates
(up to 9 glutamate)

Hydrolyzed at the brush border membrane to

monoglutamate, by the γ-
glutamylcarboxypeptidases (also called conjugases),
which are zinc dependent.

The conjugases are also found in the pancreatic juice,

and bile.
 DHFR, dihydrofolate reductase;

MRP3, multidrug resistance protein

3;

PCFT, proton-coupled folate

transporter;

THF, tetrahydrofolate;

5-FormylTHF, 5-
formyltetrahydrofolic acid;

5-MTHF, 5-methyltetrahydrofolic
acid.

Patanwala et al 2014
 Vitamin C
absorbed in ileum by active transport mechanism (sodium-
dependent, energy requiring, carrier mediated transport system).

Prior to absorption, ascorbate may be oxidized to

dehydroascorbate (DHAA, absorbed by passive diffusion).

Vitamin C crosses the cell membranes in the form of DHAA

Pectin (14.2 g/day) (mechanism unknown) and zinc (9.3 mg/day)

may impair the absorption of vitamin C

A high iron concentration present in the GIT with vitamin C

results in the oxidative destruction of vitamin C yielding2,3-
diketogulonic acid (no vitamin C activity).
NaCl reabsorption in the small
intestine and colon

Figure 21-21
 Chloride transport
The absorption of Cl- is passive in the proximal intestine
In the jejunum, Cl- moves passively through paracellular
pathways
offset net positive charge movement caused by rapid Na+
uptake couple with nutrient absorption

in the distal intestine, there is electroneutral transport of Cl-

across the luminal membrane
In the ileum and colon, uptake of Cl- across the lumen
membrane occurs through a HCO3- coupled antiport
mechanism
Requires Carbonic anhydrase to facilitate
 Calcium and Magnesium
Absorption
Ca2+ enters enterocyte passively down its
electrochemical gradient in proximal intestines

Uptake of Ca2+ in intracellular calcium stores

maintains the gradient

Ca2+ ATPase pumps calcium out to the blood

 Calcium absorption

Vit D stimulates the uptake of calcium by increasing Ca 2+ binding proteins and Ca2+ ATPase
Kopic and Gabel 2013
Magnesium

de Baaij et al 2015
Iron absorption

Feldman et al 2006
Iron absorbtion

Feldman et al 2006
Vitamin B12 assimilation
Dietary proteins contain Vitamin B12
(cobalamin)

B12 binds salivary R protein in

stomach

Pancreatic proteases remove R

protein in duodenum

Intrinsic Factor from stomach then

binds B12 in duodenum

Intrinsic Factor/B12 complex binds to

the receptor cubilin in terminal ileum
for absorption by endocytosis

In the enterocytes, B12 transferred to

transcobalaminII for transportation in
the plasma

Kumar et al 2010
Movement of Water in the Small
Intestines
Paracellular water permeability decreases from proximal to
distal in the small intestines
 Water absorption
Ingested 2000ml
Endogenous 7000ml
secretions
Salivary glands 1500ml
Stomach 2500 ml
Bile 500 ml
Pancreas 1500ml
Intestine 1000ml
7000ml
Total 9000ml
 Water absorption
Total input 9000ml
Reabsorbed 8800ml
Jejunum 5500ml
Ileum 2000ml
Colon 1300ml
8800ml

Balance in stool 200ml

Large intestine
6.4cm diameter and
110cm long

3 segments

empties into a
relatively straight
segment of the large
intestine the Rectum
Rectum - ends at the anus.
epithelial surface area is smaller than that of the
small intestine
surface is not convoluted and not as long as small
intestine
mucosa lacks villi
secretions of Large intestine are scanty, lack
digestive enzymes and consist mostly of mucus and
fluid containing bicarbonate and potassium ions
No enetrocytes but, as in the small intestine, has crypts
contain colonic absorptive cells
no endocrine cells are found in the colon
NaCl reabsorption in the colon

Figure 21-21
 Activities of the large
intestine
Stores and concentrates fecal material before
defecation
chyme enters the cecum through the ileocecal
sphincter
sphincter is normally closed,
after a meal, when the gastroileal reflex
increases ileal contractions, it relaxes each time
the terminal portion of the ileum contracts,
allowing chyme to enter the large intestine.
Movement of Water in the Colon
The colon has the lowest paracellular permeability to water
because it’s trying to solidify waste and it needs to link water
movement to transcellular ion movement
Primary absorptive process
Primary absorptive process
is active transport of Na+
from lumen to blood +
accompanying osmotic
absorption of H2O (nearly all
H20).
Normally there is a net K+
movement from blood into
colon lumen
loss of large vol of fluid
could cause K+ depletion &
also there is net HCO3
movement into lumen &
prolonged diarrhea could lead
to blood acidosis
Secretory & contractile activity – Large
intestine (colon)
Distension of colon produces a reflex contraction of
sphincter preventing fecal material flowing back into small
intestine.

About 1500 ml of chyme enters colon from small intestine

Colon also absorbs some products formed by bacteria

inhabiting this region

Undigested polysaccharides (fibre) are metabolized to

short-chain fatty acids by bacteria in large intestine &
absorbed by passive diffusion. HCO3 secreted in colon
helps neutralize these fatty acids.
 Secretory & contractile activity – Largel
intestine (colon)
 Bacteria also produce small amounts of vitamins
especially vitamin B12 and K (trace amounts)
that can be absorbed into blood
 Flatus: a bacterial product – mixture of Nitrogen
(from swallowed air at rate of 400 – 700 ml.d),
CO2 &, inflammable gases (methane, hydrogen &
H2S
 Some foods (e.g. beans contain) some CHO not
digested by intestinal enzymes & bacteria
metabolize these & produce large amounts of gas
 Innervation and contractile activity –
Large intestine (colon)
 Innervation by the vagus nerve up to transverse colon .
 contains  both efferent  and  afferent  fibres
 The  last  part  of  the  gastrointestinal  tract  receives
 parasympathetic innervation  from  the  pelvic  nerves
 Mixing  occurs  in  the  ascending  colon,  
 because  peristalsis  is followed  by  anti-­peristalsis
 gastro-­colic  and duodeno-­colic  reflexes  assisted  by  gastrin  and
 by  cholecystokinin  (CCK)  promote  peristaltic  rushes
 Slow  waves  of  contraction  move  the  content  in  the  oral
 direction  to  delay propulsion  and  increase  absorption  of  water
 and  electrolytes
 Colonic  segmentation  is  a  mixing  of the  content  by  regular
 segments  called  haustrae
 Motility & defecation: contraction of colon circular
muscle at a rate of once/30min produce a segmentation
motion hence materials remain in colon for 18 – 24 hr
thereby providing time for bacteria to grow & multiply.
 Mass movement: a wave of intense contraction generally
follows a meal 4 – 3 times/day & spreads rapidly over
transverse colon toward the rectum usually coinciding with
gastroileal reflex
 Anus – closed by internal anal sphincter composed of
smooth muscle & external anal sphincter- composed of
skeletal muscle under voluntary control
Propulsion movement activity

BER (9/min in cecum & 16/min in sigmoid)

Peristalsis

Segmentation

Mass action
GIT hormones and their
functions
Hormones affecting the large
intestine
Feces and their composition
Components Percentage of
total weight
Water 75%

Solids 25%
 Composition of total solids
Components Percentage
Cellulose & other ingested fiber Variable (30)
Bacteria 30
Inorganic material (mostly 15
calcium and phosphates)
Fat & fat derivatives 10 to 20
Desquamated mucosal cells, Trace (2-3)
mucus and & small amounts of
digestive enzymes
 Anal Sphincters
Internal anal External anal
sphincter sphincter
Smooth muscles Skeletal muscles

Involuntary Voluntary

Autonomic somatic
 Defecation
It  is  a  complex  act  involving  both  voluntary  and  reflex
 actions  in  colon,  rectum,  anal sphincters  and  many  striated
 muscles  (diaphragm,  abdominal  and  pelvic  muscles)
Distension of recto-sigmoid region with feces intiates reflex
contraction (intrinsic  defaecation  reflex and  a  strong,  spinal
 reflex ) of its musculature & the desire to defecate.
rectum  is  usually  empty,  and  its wall  has  a  rich  sensory  supply
Internal sphincter relaxes when the rectum is distended.
External anal sphincter is maintained in the state of tonic
contraction & moderate tension of rectum increases the force of
contraction.
When pressure reaches 55mmHg, the external & internal
sphincter relaxes & there is a reflex expulsion of the contents of
the retum
 Voluntary defecation
Intitiated by straining if pressure of <55 mmHg no
reached
With straining the abdominal muscles contract, pelvic
floor is lowered 1-3 cm & puborectalis muscles
relaxes
Anal rectal angle relaxation of puborectalis the angle
is reduced from 90oC to 15oC or less
 Frequency of defecation

Once every 2-3 days

Once a day

Three times a day

 Intestinal bacteria
Found in
Jejunum (few if any)
Ileum (few)
Colon (large numbers)

3 types of bacteria
Pathogens
Symbionts [benefit host (synthesis vit K and vit B12,
B1 riboflavin) & vice versa (use ascorbic acid and
cyanocobalamin]
Commensals (have no effects on host & vice versa)
 Spatial and temporal aspects of
intestinal microbiota composition

SEKIROV et al 2010
Effects of Gut bacteria on overall
health
Short-chain Fatty Acids
Produced in the colon and absorbed from it

2–5-carbon weak acids formed by the action of colonic bacteria

complex carbohydrates, resistant starches, and other components of the
dietary fiber,

Average normal concentration of about 80 mmol/L in the lumen (70-

140 mmol/L depending on diet).
95% absorbed colonic epithelial cells

Forms of Short chain fatty acids

About 60% is acetate,
25% propionate
15% butyrate.
Purpose of Short chain fatty
acids
absorbed by specific transporters present in colonic
epithelial cells
in part by exchange for H+,
Linked to Na absorption (Na-SCFA)

metabolized and make a significant contribution to the total

caloric intake

exert a trophic effect on the colonic epithelial cells and

combat inflammation

Helps to maintain acid base equilibrium (exchange for H+)

Effects of Gut bacteria on overall
health
Benefits of SCFA
Pathogen-host-microbiota interactions
and outcome of infection.
The role of microbiota in inflammatory
bowel disease (IBD) pathogenesis
Usually  the  recto-­sigmoid  area  is  involved,  a  location  where  the  faecal  content  is
 moved  to  and  fro for  varying  periods