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DIGESTION

LECTURE 1
What is the gastrointestinal or digestive system?

The gut is a series of hollow muscular tubes that go all the way from the
mouth down to the anus. The series of muscular tubes is called the
digestive system. Its also called the gastrointestinal tract (GI tract) or the
alimentary tract.
Alimentary means to nourish.
When we eat, we take in food into our mouth, a process of what we call
INGESTION.
Food in the mouth is mixed with saliva. Saliva begins to dissolve the food
as the teeth grind and cut it. The tongue moves the food around the
mouth and it gets masticated (or chewed) to form a bolus.
The bolus gets pushed to the back of the mouth, by the tongue, into the
upper part of the gut which is called the pharynx. Food in the pharynx
stimulates the swallowing reflex.
From the pharynx, the ingested food goes down the oesophagus.
The food then passes through the stomach and gets mixed with stomach
secretions.
Ends up forming a pulpy matter called chyme.
The chyme gets emptied into the very long small intestine in a
controlled manner.
From the small intestine it goes to the large intestine.
Then it is released from the body via the anus.

Accessory glands and organs


The accessory glands and organs secrete their substances into the hollow lumen
of the gut. These include

Salivary glands
Pancreas
Liver- synthesises and secretes bile
Gallbladder- where the bile is stored
Tongue

Functions of the gastrointestinal system

Absorbing nutrients

Absorbing fluids and electrolytes


Secrete gut hormones that control secretions of things like bile or
pancreatic secretions.
Excretion ( of things thats left in the body) by the process of defecation
(pooh)
Immune functions- the entire lining of the gut is in direct contact with the
external environment. We take in lots of different foods and those foods
may have nasty pathogens in them. There are millions of immune cells in
the lining of the gut that attacks potential pathogens before they affect
the body.

How does the gut move ingested food?


MOTILITY is the propulsion of food through the gut.
Motility/contraction involves layers of smooth muscle in the gut.

This picture shows the transverse section of the small intestine. The inner hollow
part of the gut is referred to as the LUMEN. The lining of the lumen is called the
MUCOSA. In the small intestine, the mucosa has huge finger-like projections. This
just increases the surface area for the absorption of nutrients in the small
intestines. The inner layer of smooth muscles in the lining of the small intestine
is called CIRCULAR LAYER and the outer layer is called the LONGITUDINAL
LAYER.
Smooth muscle layers form a functional (electrically coupled) syncytium

The cells in the circular muscle layer and in the longitudinal smooth muscle layer
are electrically coupled to each other and are joined by gap junctions. The gap
junctions are low distance pathways that allow ions to move from one cell to the
next and thus all the excitation to spread from one smooth muscle to the next.
Smooth muscle cells do not contract without excitation.

After excitation smooth muscle cells contract (shorten)

Once the smooth muscle cell is excited, it contracts or shortens in length.


Smooth muscle contraction involves thick myosin filaments and thin actin
filaments. The thick myosin filaments have heads that attach to or detach from
the thin actin filaments, causing it to slide over or from cross bridges which leads
to cell shortening.

What happens when the gut circular and longitudinal muscle layers
contract?
Briefly discuss oesophageal peristalsis as an example of gut motility
In context of oesophageal peristalsis- when the food is chewed and turned into
bolus, it goes to the back of the mouth through the pharynx and then moves all
the down through the oesophagus via the process of what we call peristalsis. Its
described as though like pushing soft banana through a straw.

The oesophageal peristalsis involves excitation and contraction of circular muscle


layers. From the picture you can see that above the bolus, we have constriction
of the layers and beneath the bolus we have shortening (which involves
excitation and contraction of the longitudinal smooth muscle).
The interesting thing about peristalsis is that there are very strong muscular
contractions. So you can actually hang upside down, and it will still allow you to
swallow your food and pass it down the oesophagus.

Skeletal muscles are also present in the gut


Smooth muscle doesnt have regular striations but skeletal muscles do, which
give it a patterned appearance. They have regular striations because their actin
and myosin are more organised than that of smooth muscles.
Smooth muscles are innervated by autonomic nerves, so the process in
involuntary whereas skeletal muscles are innervated by somatic nerves and so
the process in voluntary.
Within the gut we have thickening of muscles called sphincters and these are
either made of smooth or skeletal muscles. These control the passage of food
from the top to the bottom and prevent backflow of food within the gut.
There are 7 sphincters within the gut:
1.
2.
3.
4.
5.
6.
7.

Upper oesophageal
Lower oesophageal (gastro oesophageal sphincter)
Pyloric
Oddi (hepatopancreatic)
Ileocecal
Internal anal
External anal

The upper oesophageal and the external anal sphincter are both made of skeletal
muscle. The rest of the sphincters are made of smooth muscles.

Neuronal control of gut functions


The nerves in the gut include:
1.
2.
3.
4.

Sensory nerves
Somatic nerves
Autonomic nerves
Enteric nerves (Gut brain)

Organisation of nervous system in the gut


We have a length of gut tube. When we eat and swallow food, we are
going to have a bolus of food in the gut tube. The bolus needs to be
moved downwards through the gut tube. When it moves downward, it is
detected by stretch receptors as the wall of the gut is extended. These
stretch receptors are the ends of sensory nerves. They activate the
sensory nerves and pass the signals up to the central nervous system.
The information is integrated and we get altered output via somatic
nerves (efferent nerves) that innervate the skeletal muscle.
In the gut, skeletal muscles function to control swallowing (where pharynx
and upper oesophageal is involved) and coordinating defecation. So these
two processes are voluntarily controlled by the somatic nerves.
The somatic nerves also activate autonomic (involuntary) nerves which
innervate glands and smooth muscle. This results in increasing motility
ans secretion and thus moves the bolus down the tube.
Autonomic (involuntary) nerves innervate smooth muscle and
glands in the gut wall

Running along the circular smooth muscle, we see the autonomic nerves
(shown in yellow in the picture). The autonomic nerve terminals have a
few varicose (beaded appearance). In each of the varicosities (or the
swellings), there are synaptic vesicles (shown in green) that contain
chemical neurotransmitter.
During activation of the autonomic nerves, action potentials run down the
nerve terminals, releasing neurotransmitter from the varicosities which
then act on smooth muscle cells. The smooth muscle cells have receptors
specific for the neurotransmitter. Depending on the receptor or the
neurotransmitter, there is a whole series of intracellular pathways which
either increase or decrease contraction force.
Autonomic (parasympathetic and sympathetic) control of the gut
motility/contraction and glandular secretions
SYMPATHETIC activation of the gut leads to a decrease in motility and a
decrease in the secretion.
PARASYMPATHETIC activation of the gut leads to an increase in motility
and increase in secretion. Secretion includes things like hormones,
digestive enzymes or mucus to lubricate the food.

Enteric nervous system (GUT BRAIN)


The system is called gut brain because the enteric nerves can actually
control gut functions without any input from the central nervous system.
So the system got its own little brain to control gut function within the gut
itself.
Sensory nervous reside within the wall of the gut. When stretch receptors
are activated, the sensory neurons synapse with the enteric neurons.

Those enteric neurons then alter the motility and the secretion of the gut
within the gut walls.
Enteric nervous system is made up of two interconnected groups
of neurons/ two intrinsic nerve plexuses:
1. Myenteric plexus
Located between circular and longitudinal smooth muscle layers
and runs along the entire length of the gut.
Controls motility within the gut

2.

Submucosal plexus
Underneath the mucosa we have the submucosal layer.
Not along the entire length of the gut, but in discrete regions.
Controls absorption of nutrients, local blood flow and secretions of
hormones and mucus.

The enteric neurotransmitters (research in progress)

Most enteric neurons contain multiple neurotransmitters.


They can be EXCITARORY or INHIBITORY, depending on the type of
neurotransmitters they have in them.
If the enteric nerve contains acetylcholine, it is an EXCITATORY
neuron.
If it contains nitric oxide, its an INHIBITORY neuron. Nitric oxide
relaxes the smooth muscle cells.

Neuronal control of the smooth muscle sphincters.

The sphincters are made of rings of circular smooth muscles and


normally the sphincters are in constant state of constriction (or the
smooth muscle cells are contracted)
The smooth muscle sphincters are innervated by both the enteric
nerves that reside within the gut (and they are referred to as
intrinsic neurons) as well as the extrinsic autonomic nerves that are
coming in from outside the gut to innervate the sphincters.
We relax the sphincters by activating parasympathetic nerves or by
releasing nitric oxide from the inhibitory nerves in the myenteric
plexus.
Sympathetic activation of the gut tube inhibits contractions (leads to
relaxation of the smooth muscle cells). Whereas sympathetic
activation of the smooth muscle cells in the gut sphincters contracts
them, thus closing of the sphincters.

SUMMARY TABLE: Neuronal control of gut


functions:
sympathe parasympat
tic
hetic

Myenteri
c
(excitato
ry or
inhibitor
y)

Submuco
sal
(excitator
y or
inhibitory
)

Motility
Secretio
ns
Sphincte
rs
(smooth
muscles)

Rows 1 and 2 = increases, decreases or no change. Row 3 = constricts, relaxes


or no change.

Summary = control of gut functions by nerves


(1) Autonomic nerves innervate the gut:

Parasympathetic nerve activation increases contractility/motility & gut


secretions (and relaxes smooth muscle sphincters)
Sympathetic nerve activation decreases contractility/motility & gut
secretions (and constricts smooth muscle sphincters)

(2) Enteric nerves innervate the gut:

Activation of myenteric neurons (enteric nervous system) increases


contractility/motility (and controls sphincter constriction)
Activation of submucosal neurons (enteric nervous system) increases gut
secretions.

Revision question at the end of lecture


Sympathetic nerve activation will cause the following effect on gut
function:
(A) increased oesophageal peristalsis
(B) increased gastric acid secretion
(C) relaxation of the pyloric sphincter
(D) decreased intestinal contractions

Lecture 2
Gastrointestinal motility

The duodenum is about 25 cm in length. It is followed by a long


section of the gut called jejunum-which is usually about 2.5 m.
Underneath that there is an even longer ileum, which is about 3.6 m
long in average 70 kg male human.
The small intestine starts with pylorex sphincter (between the
bottom of the stomach and the start of small intestine) and ends
with the ileocecal sphincter (between the ileum and cecal).

Digestive process in the small intestine

When we swallow food, it goes into the stomach and gets mixed
with gastric secretions and we end up with a pulpy semi-fluid matter
called CHYME.
The chyme is then emptied from the stomach into the small
intestine and is mixed with digestive juices that are being secreted
into the lumen of the small intestine.
Within the small intestine, almost all the chemical digestion of our
food is completed and nearly all nutrient absorption occurs. They
get absorbed across the wall of the small intestine into the
bloodstream and dispense through the body.
When food gets to the bottom of the small intestine, the undigested
remains that are left behind gets moved down to the large intestine.
Distension (stretching or filling of the stomach) leads to activation of
stretch receptors (thus activating sensory nerves). These pass
through CNS and lead to increased parasympathetic activation of
the underline small intestine.

Segmenting contraction (segmentation)

These are contractions with localised constrictions along the length


of the small intestine-which makes it look like a string of sausages.
It allows mixing of the food or chyme emptied from the stomach
with the digestive secretions into the small intestinal lumen.
We dont get much downward propulsion of the food. It is essentially
two steps forward and one step backward.
During segmentation, the constrictions result from activation of the
parasympathetic nerves (results from stretch of the stomach) and
also from activation of local myenteric neurons.

When most of the meal nutrients have been absorbed, the segmenting
contraction are replaced by the MIGRATING MYOELECTRIC COMPLEX.

Migrating myoelectric complex (MMC)

Involves peristaltic contractions (like squeezing food through the


system) of several adjacent segments of the gut and moves the
content from below the stomach down to the large intestine.
It takes 2 hrs for the food to reach the large intestine.
The MMC removes any undigested remains down to the large
intestine. Lack of MMC leads to a massive over growth of bacteria
within the small intestine.
If we then take another meal, the MMC stops and it is then replaced
by segmenting contraction (mixing contractions).
What triggers the MMC is when the chyme, within the small
intestinal lumen, goes to an alkaline level- so the pH rises.
MMC is also triggered by a hormone called MOTILIN. As the plasma
level of motilin increases, it triggers MMC.
Feeding inhibit the reduce of motilin.
The MMC is modulated by both extrinsic neurons and autonomic
neurons (ENS and ANS).

Digestive process in the large intestine

The large intestine is involved in the digestive process of mixing


contractions (also known as haustrations). By the time the luminal
contents get emptied from the small intestine to the large
intestines, there are actually very few nutrients left.
There is a small amount of chemical digestion happening by
bacteria residing the large intestine called enteric bacteria.
Absorption of water and electrolytes also take place in the large
intestine.
Propulsion actions called mass movements move the large
intestinal content down to the rectum. Form this point we excrete
any of the remains that are left behind. Excretion is done via process
of defecation.
Once the content is emptied from small to large intestine, it takes
about 12 hrs for a normal healthy person to start defecation.

Haustral contractions

The colon has pockets or sacs that look segmented. They are
referred to as haustra or singular haustrum. These haustra results
from localised stretch of the large intestinal wall and activation of
the myenteric nerves of the enteric nervous system-which leads to
localised constrictions.
In the large intestine, the wall of the colon is made of circular
smooth muscle.
The longitudinal smooth muscle layer is specialised in the large
intestine into three strips of muscle called the teniae coli.
It takes about 30 minutes to move the food content through three of
the haustra.
So in a normal healthy person, it takes time for the food to slowly
move through the intestines. And that is a good thing because then
there is more time for absorption of water and electrolytes.

Absorption and storage in the colon

So the colon is essentially functions for absorption of water and


electrolytes but also for storage of the forming faecal material until
the process of removal through body via defecation.
The picture above tells you the state of food at different parts of the
colon as it moves over time.

Mass movements/power propulsion

The mass movement involves simultaneous contraction of large segments


of the large intestine, all the way from caecum to sigmoidal colon. The
content is squeezed downward in a long contractile wave.

We end up with a constrictive ring of the colon (smooth appearance) and


we lose the sacs of haustra.

The contraction are long in duration

Tend to have 3-4 per day (up to 10 per day). Usually happens after
breakfast.

The mass movements are triggered by filling of the stomach and filling of
the duodenum. This is referred to as gastrocolic and duodeno-colic
reflexes. As we get filling of the stomach, this leads to stretch or
distension, which activates stretch receptors through sensory nerve
activation. This activates the parasympathetic nerves of small and large
intestines.

Healthy adults control the location and timing of defecation

Defecation is defined as the removal of faecal matter from the body.


Involves several structures.

A mass movement moves faeces from


the sigmoidal colon into the rectum:
What needs to happen to remove the faeces
from the body?

Contraction of rectum
Relaxation of both internal and
external anal sphincters.

Defecation reflex

The process of mass movement moves the faecal matter from the
sigmoid colon down to the rectum. This then leads to activation of
the stretch receptors (thus activating sensory nerves).
The sensory nerves then synapse with spinal cord neurons. We then
get an increase activation of parasympathetic nerves which
innervate the rectal wall.
This increases rectal contractions and relaxes inter anal sphincter.

Activation of sensory neurons also increases the activation of the


myenteric and submucosal plexuses.
Parasympathetic activation and enteric nerve activation leads to
increased secretion of mucus that lubricate the faecal content being
eliminated from the body.
In cases when we decide not poop, what happens is the faecal
content moves back up the sigmoid colon through the process of
retrograde peristalsis (reverse peristalsis), until another mass
movement comes down.
When we dont want to poop, we have conscious control (by the
cerebral cortex) of the defecation reflex. This activates the somatic
motor nerves which lead to constriction of the skeletal muscles of
the external sphincter.
And then if we decide to poop, we get inhibition of these somatic
motor nerves, which leads to relaxation of the external anal
sphincters.
This process is a learned process. Like babies are taught to control
their defecation.
If the faeces are particularly hard, we tend to strain or increase the
abdominal pressure and this is referred to as Valsalva manoeuvre.
In elderly people with history of cardiovascular diseases, straining
/Valsalva manoeuvre can lead to a sudden drop in blood pressure
and cause them to faint.

Scenario
A healthy 21 year old woman eats a large meal and then takes a 3 hour ride on a
bus without a toilet. 20 minutes after eating, the woman feels a strong urge to
defecate, but manages to hold it.so that downward mass movement of the
content has occurred and the defecation reflex is initiated. Which of the following
have occurred in this woman?

1. Relaxation of the internal sphincter?


Yes, initiating the defecation reflex relaxes the smooth muscle of the
internal sphincter
2. Contraction of external sphincter?
Yes, because we are not finalising the defecation reflex yet.
3. Contraction of the rectum?

Yes, there will be contraction of the rectal wall because faecal content is
moved downwards towards the anal passage as part of the defecation
reflex.
4. Retrograde peristalsis?
Yes, because she is holding it back so the content will move back up.

Revision questions at the end of the lecture


1. What triggers the defecation reflex? How do we control the final part
of this reflex?

2. Hirschsprungs disease is associated with aganglionic sections of the


large intestine. What is meant by aganglionic and why does this
disease lead to bowel obstruction and constipation?

Aganglionic means that there is a lack of intrinsic neurons in the


wall of the gut. This disease leads to bowel obstruction and
constipation because the

Lecture 3
What happens when the intestine lacks intrinsic parasympathetic
and myenteric nerves?
Hirschsprungs disease (congenital aganglionic megacolon)
Enlargement of the colon (megacolon) resulting from an aganglionic section of
the bowel.

The innervation of the gut doesnt develop from the bottom of the
gut.
So the bottom section of the gut lacks intrinsic neurons (lack
enteric, myenteric, submucosal and parasympathetic neurons).
The colon becomes enlarged because the faecal material is not
getting removed from the body. It is accumulating within the colon,
distending it and causing it to become enlarged.
Normally, during the defecation reflex, the presence of faecal matter
activates sensory stretch receptors that lead to parasympathetic
activation of the rectum. This stimulates rectal contractions to move
the faecal matter downwards relaxes the internal anal sphincter.
But in Hirschsprungs disease, since there is no parasympathetic or
enteric activation of the rectum and the internal anal sphincter,
motility is not stimulated. Hence we get an accumulation of faecal
matter within the colon.

Diagnosis

If a baby fails to pass a bowel movement (meconium) within the first 48


hours after birth, they are tested to see if the bowels are functioning
normally.
Staining histological sections with cholinesterase (a marker for acetyl
choline). It is the main excitatory neurotransmitter that stimulates motility
and relaxes the internal anal sphincter.

Treatment

Surgical removal of the section of the gut that lacks neurons (aganglionic
section).the remaining bit of the gut is then reattached to the

sphincters at the bottom.

The stomach

Lower
oesophageal
sphincter

The mucosal lining of the stomach is referred to as rugae of


mucosa.
As the stomach fills with food, the wrinkled mucosal lining smoothes
out.
The stomach itself has slightly different organisation of the muscle
layers compare to small or large intestine.
In addition to the longitudinal and circular muscle layers, the
stomach also has an oblique muscle layer. This layer help with the
turning contractions after food is eaten.
The turning contractions are referred to as pyloric pump and it job
is to mix all the food with stomach secretions, break down the food
and carry out chemical digestion.

Digestive process in the stomach

Functions as a storage area.


We ingest food at a faster rate than it can actually be chemically
digested.
The stomach volume can go from 50 ml upto 4 L. The wrinkles
smooth out to fill with food.
Mechanical digestion and propulsion include pyloric pump and
turning contractions of the stomach. It propels the food up and
down within the lumen of the stomach.
The peristaltic waves mix food with gastric secretions to form
chyme- which is then emptied into duodenum. The rate of

emptying of chyme is dependent on the type of food we eat. Fats


and carbohydrates are emptied out the slowest.
Protein digestion initiated in the stomach via an enzyme called
pepsin.
There is secretion of intrinsic factor which allows the body to
absorb vitamin B12. We need vitamin B12 in order to produce
mature red blood cells.
Absorption of a few fat-soluble substances also occurs in the
stomach.

Gastric secretions
Gastric glands are located under gastric pits in the mucosal lining of the
stomach. They contain four main types of secretory cells.

The lumen of the stomach is lined by a single layer of epithelial cells


called the MUCOSA.
The pits are in the wall of the mucosa.
Underneath the wall there gastric glands

Within the gastric glads there are four different types of secretory cells:

1. Mucous cells- secrete mucus and lubricate the food thats being
swallowed.
2. Parietal cells- secrete intrinsic factors essential for absorption of
vitamin B12 and HCl. These are the acid secreting cells within the
stomach.
3. Chief cells- secretes pepsinogen (inactive form of pepsin)
4. Enteroendocrine cells- secretes gut hormones

Activation of pepsinogen from pepsin

Mucos
a

Gastric
glands

The gastric glands contain the chief cells that secrete pepsinogen
and it contains the parietal cells that secrete hydrochloric acid and
intrinsic factor.

The optimal pH for activating pepsinogen is a pH of 2. Once the pH


goes above 4.5, we get inactivation of pepsinogen.

So in a very acidic environment, the pepsinogen is activated to


pepsin.

That pepsin breaks down protein into peptides.


Why are gastric juices so acidic?

Gastric luminal pH = 23 (~1 with maximum HCl secretion)


Cellular pH = 7.0 - 7.2
Arterial blood pH = 7.4

1. Because We need an acidic environment to activate pepsin form


pepsinogen.
2. Because the acidic environment kills of ingested pathogens or bacteria
(sterilizes the food eaten)
3. Because we eat a lot of plant material. Plant cell walls are made of
cellulose and cellulose is almost indestructible. The acidic environment
in the stomach break down this cellulose from the plant material we
ingest.
With the acidic environment in the stomach, it is very important
to protect the stomach. There are 3 mechanisms as to how the
stomach protects itself from the acid.
The stomach mucosa is protected from corrosive acidic gastric juice by:
(1) There are specialised cells that secrete a bicarbonate (HCO3-) rich mucous.
Bicarbonate is a hydrogen ions buffer so it mops up free hydrogen ions being
secreted on the mucosal lining of the stomach.
(2) Mucosal epithelial cells joined by tight junctions. So that prevents any
leakage of the acidic chyme through the underline cells beneath the mucosal
layer.
(3) Damaged epithelial cells shed and rapidly replaced by division of
undifferentiated stem cells. So the mucosal lining of the gut and also the small
and large intestine is replaced every 3-5 days.

Acid secreting cells


Acid secreting cells in the stomach are called parietal cells. They are also
called oxyntic cells.
Mucosa

Lumen

H+

Theres a very high concentration of the hydrogen ions in the lumen


because of the very low pH relative to H+ concentration within the
parietal cells.
Within the parietal cells there are lots of mitochondria. 40 % of the
cell volume is made up of mitochondria. So there is active transport
going on within these cells to help with the process of acid
secretion.

Where do parietal H+ and Cl- come from?

CO2 that is either diffusing in from outside the cell or being


produced within the cell via process of metabolism, combines
with water or we get carbonic acid.
The carbonic acid dissociates rapidly into hydrogen ions (H+) and
bicarbonate ions.
The bicarbonate ions are exchanged via anion antiporter for
chloride ions. So the bicarbonate ion end up in the veins and they
make the pH of the veins higher than the pH of arteries that are
also supplying the stomach. So we end up with what is referred
to as ALKALINE TIDE.
The chloride ions diffuse out of the cell via chloride channel, into
the lumen of the stomach.
To get hydrogen ions out of the parietal cell and into the lumen, it
needs to involve active transport because they are being moved
against a very high concentration gradient.
There is hydrogen/potassium ATPase pump (or proton pump) in
the luminal membrane. These use the energy provided by
hydrolysis of ATP to actively pump out of the parietal cells the
hydrogen ions in exchange of potassium ions being pumped into
the cell.
This process is referred to as BASAL ACID SECRETION. It occurs in
the parietal cells all the time.

How do we increase acid secretion above the basal


levels?

Activation of the parietal receptors by histamine, gastrin or acetylcholine


enhances HCl secretion (above basal levels).

Proton

Lume
n

GASTRIN (the gut hormone being secreted from the G cell of the
stomach) acts on receptors called G type receptors.
Histamine acts on H-type receptors.
Acetylcholine comes from parasympathetic and enteric nerves and
acts on muscarinic receptors.
When the hormone/neurotransmitter has interacted with the
receptors, there will be a cascade of intracellular pathways involving
second messengers.
Within the parietal cell, there are pre-formed proton pumps (shown
In red in the picture) sitting on the vesicles.
Once the receptor is activated, the pre-formed proton-pumps are
inserted into the luminal membrane, thus increasing the amount of
hydrogen being secreted from the cell or increasing acid secretion
above the basal levels.

How to treat excess gastric HCl secretion: Proton


pump inhibitors (PPIs) or antihistamines?
There is a range of options. We can inhibit the receptors that lead to an
increase in acid secretions such as the gastrin, histamine and Ach

receptors. We could also inhibit the proton pumps in the luminal


membrane.

The proton pump inhibitors (PPIs) would be more effective in


treating excess gastric HCl secretion because we are blocking all
pathways for increasing receptor mediated acid secretion. We are
blocking the activation of muscarinic receptors, gastrin receptors
and histamine receptors.
On the other hand, if we use an antihistamine, we are only blocking
the effects of histamine to increase acid secretion.

What leads to the secretion of acetylcholine,


histamine and gastrin? How is increase in acid
secretion associated with ingestion of a meal?
There are 3 phases of gastric acid secretion associated with ingestion of a
meal.
1. The cephalic phase
2. The gastric phase
3. The intestinal phase

The cephalic phase


stimulus

Sight
Smell
Touch
Thought of food
Taste
Chewing
Swallowing

pathway

Stimulus to
parietal cells

From the brainstem


(medulla oblongata) =
activation of
parasympathetic nerves
(via the vagus)
innervating parietal and
G cells.

The gastric
Stimulus

After swallowing
the food, there is
distension of the
stomach so
stretch receptors
are activated.
Increase in pH.
Increase in Semi

Secretion of
acetylcholine
from
parasympathetic
nerves.
Secretion of
gastrin from G
cells.
The Ach and
gastrin then act
on
enterochromaffinlike cells (ECL) to
cause secretion
of histamine.
All this leads to
receptor
mediated acid
secretion.

phase
Pathway

Local (enteric) and long


autonomic
(parasympathetic)
reflexes: parietal and G
cells

Stimulus to
parietal cells

Secretion of
acetylcholine
from
parasympathetic
nerves.
Secretion of
gastrin from G
cells.

digested protein

The Ach and


gastrin then act
on
enterochromaffinlike cells (ECL) to
cause secretion
of histamine.
All this leads to
receptor mediated acid
secretion.

The intestinal phase (this is the


inhibitory phase of gastric acid)

Stimulus

Acidic chyme is
emptied from
stomach into
duodenum thus
causing
distension of
stretch receptors
and increase
acidity
Presence of
protein digestion
products

Pathway

Stimulus to
parietal cells

Intestinal endocrine
secretions
(enterogastrones:
secretin, gastric
inhibitory peptide)

Decreased acetylcholine
and gastrin secretion
thus decreasing receptor
mediated acid secretion.

Inhibition of vagal nuclei


in medulla + local
neuronal reflexes

What can go wrong during acid secretion?


Three things can happen:

(1) It can cause ulceration of the stomach or


duodenum

Ulcers can form when the gastric/duodenal mucosa is damaged


Sensitive, raw patches which form a break in the lining of the stomach
(gastric ulcers) or the duodenum (duodenal ulcers).
Causes include: High acid and pepsin content of the chyme in the
stomach, Irritation in the lining of the stomach, Poor blood supply to the
stomach (which can affect underline cells),Poor mucous secretion
(particularly bicarbonate mucus that protects the mucosal lining of
stomach) and Infection via bacteria (Helicobacter pylori).
Treatment: antibiotics and acid suppressing drug (usually PPI).

(2) It can get into the wrong places (gastrooesophageal reflux)

Heartburn or (gastroesophageal reflux disease/GORD/GERD)


The burning pain that occurs when acidic gastric juice goes back up into
the oesophagus
Caused by failure of the lower oesophageal sphincter that would normally
prevent this reflux.
Most likely to occur after excessive drinking and/or eating, plus by
conditions that force abdominal contents upwards (like obesity or
pregnancy , the acidic chyme jiggles up and down)
Can be treated with antacid preparations (or H2 receptor antagonists,
proton pump inhibitors)

Gastroesophageal reflux in babies:

~20% of babies have GERD because they have an immature lower


oesophageal sphincter so they get leakage of acidic chyme back up into
the oesophagus.
Treatment = upright position, small & frequent feeding, antacids,
breastfeeding mothers to avoid caffeine.

(3) It can become defective


Causes of defective gastric acid secretion

Surgical removal of stomach


Autoimmune gastritis (achlorhydria). Achlorhydria = absence of
hydrochloric acid in the gastric secretions
Pernicious anaemia results from VitB12 deficiency. The parietal cells are
not secreting intrinsic factor.
Neurological disturbance like something that damages the vagus.

Revision questions at the end of lecture

1. You take tablets containing acetylcholine and histamine. What would


prevent all of the resulting gastric HCl secretion?
(A) Histamine (H) receptor inhibitor
(B) Muscarinic (M) receptor inhibitor
(C) H+/K+ ATPase pump inhibitor
(D) Gastrin (G) receptor inhibitor

2. Explain why proton pump inhibitors (PPIs) are now considered more
effective than antihistamines for the treatment of digestive disorders
involving inappropriate acid secretion (e.g. gastric ulcers). Why antibiotics
are also frequently prescribed to patients with gastric ulcers?

Lecture 4
describe the roles of bile, cholecystokinin (CCK) and secretin in fat
emulsification and digestion
-

Bile: the liver synthesizes and secretes bile. Bile is store in the gall
bladder in between meals. Bile is made up of bile salts (help to emulsify
fats in the small intestine), cholesterol (precursor of bile salts), lecithin (a
phspolipid which combines with bile salts to emulsify fats), electrolytes
and water (contains bicarbonate which neutralises acidic chime in
duodenum) and bile pigments (produced by breakdown of haem).
Cholecystokinin (CCK): Fats in the duodenal lumen stimulate
cholecystokinin (CCK) secretion from enteroendocrine cells. CCK levels
increases when we eat a fatty meal. Presence of fats in the duodenal
lumen in the chime, cause the gall bladder to contract. Relaxes the
hepatic pancreatic sphincter. These cassue secretion of bile. Acts on acinar
cells containing pancreatic enzymes and casues their secretion. Pancreatic
lipase and co lipase. Fats take long time to be digested, so increase in
fatty chime in the stomach in the inhibitory feedback makes CKK slow
down release of fatty chyme. Inhibits motility of stomach. Constricts
pyloric sphincter between duodenum and stomach which slows down
stomach emptying.
Secretin: neutralises the

explain the process of fat digestion and absorption:


-

Fats exist in the form of triglycerides, fat soluble vitamins and cholesterol.

Mixed with water chyme in the stomach, and the triglycerides are
insoluble in the chyme. End up with bilayer of water chyme and large fat
globules.
Main enzyme for fat digestion is pancreatic lipase which is water soluble.
Large fat globules need to be broken down to smaller ones to speed up
digestion.
So fat globules need to be emulsified.
The fat globules are emulisified with bile salts and lecithine.
Emptied from stomach into duodenum. Within duodenum, there are
contractions to help break down the large fat globules, and bile salts and
lecithine present and which have hydrophobic and hydrophilic ends, and
the hydrophilic bit sticks out to watery chyme to while hydro phobic bits
stick to middle of emulsion droplet, preventing coalition.
Fat emulsion droplets have Triglycerides, fat soluble vitamins and
cholesterol in the middle and the droplets have net negative charge.
Digestion occurs using pancreatic lipase with cofactor co lipase, and the
Triglycerides are broken down to fatty acids and monoglycerides.
Emulisifying agents sit all over the outside of the droplet. The pancreatic
lipase cannot get in, so requires co lipase. Co lipase attaches to pancreatic
lipase and bile salts, moves aside bile salts and allow entry of lipase into
emulsion droplet. To digest TAG.
The product diffuse directly through the cell membrane and to the
absorptive cells.
Also forms tiny fat droplets called micelles.
Centre of micelles contain breakdown products of digestion of TAG ( MG
and FA, cholesterol)
Fatty acids and MG diffuse through the cell membrane into absorptive cell,
they get packaged in the ER. Cell membrane formed around and they
reform TAG and surrounded by Cell membrane ( chylomicrons)
Too large to be absorbed into capillaries
Taken up into lacteals of lymphatic system , and end up in blood via
venous return

discuss how the entry of bile into the duodenum is regulated by


cholecystokinin (CCK), secretin and vagal/parasympathetic nerve
activation
-

Acidic, fatty chime entering the duodenum causes release of CCK and
secretin from duodenal wall entero endocrine cells.
CCK and secretin enter the bloodstream.
Bile salts and secretin transported via bloodstream stimulate liver to
produce bile more rapidly.
Vagals stimulation causes weak contractions of the gall bladder
CCK (via bloodstream) causes gall bladder to contract and hepatopancreatic sphincter to relax and bile enters duodenum
Bile salts reabsorbed into blood.

discuss how inhibitory feedback from the duodenum can control


stomach emptying:
-

In the duodenal lumen, factors such as high concentration of fats, increase


in concentration of amino acids, increase in acidity, hypertonicity, and
distension causes activation of hormone secretion and neuronal activation
to cause inhibition stomach emptying into small intestine.
Increase in fat levels increase in secretion of enterogastrones, causes
release of CKK which causes increase in plasma CKK, constricts pyloric
sphincter and decreasing stomach motility.
If too much chime emptied in duodenum, stretches duodenum. This
activates sensory stretch receptors, activates enteric neurones. By enteric
nerve action, inhibition of stomach motility and constriction of pyloric
sphincter occurs.
Long term inhibition involves autonomic involves sensory neurone
activation, inhibition of PNS and activation of SNS which acts to decrease
stomach motility.

Whether the bile will be secreted into the duodenum or


enter the gall bladder depends on the relative pressures in
the gall bladder, bile ducts and the sphincter of oddi. If
sphincter is closed, pathway of least resistance is towards the liver
so bile will enter the gall bladder. During a meal, gall bladder
contracts and squeezes bile acid out and the sphincter opens.
Gall bladder stone:
Formed when cholesterol in bile greater than bile salts concetration
in bile. Auses increased water and bile salt absorption.
GB stones may obstruct cystic duct, can lead to inflammation of the
gall bladder. When GB stones block common bile duct, causes
jaundice and deficiency of fat soluble vitamins
Stones can occur anywhere
Treatment includes Dietary modifications limiting or eliminating fatty
foods and dairy products, Surgery to remove the entire gall bladder
(cholecystecomy), or stones from bile ducts and Lithotripsy machine
generates soundwaves to shatter stones.

Without gallbladders, you need to watch amount of fats intake in the


body.
You can still produce bile ( made in the liver) in response to bile salts
being released into the hepatic portal vein.
You will lose controlled secretion of bile associated with digestion of
fatty meal.

Lecture 5
describe the roles of pancreatic (exocrine) secretions in fat, protein
and carbohydrate digestion

The exocrine pancreas secretes alkaline pancreatic fluid to neutralise the


acidic content of Chyme.
It also secretes pancreatic enzymes. Pancreatic digestive enzymes consist
of :
Inactive precursors of proteolytic enzymes (trypsin, chymotrypsin,
carboxypeptidase and elastase) = no autodigestion
Active enzymes lipase, cholesterol esterase, phospholipase (fats), amylase (carbohydrates), ribonuclease & deoxyribonuclease (nucleic
acids)

discuss how the entry of pancreatic secretions (alkaline fluid and


enzymes) into the duodenum is regulated by cholecystokinin (CCK),
secretin and vagal/parasympathetic nerve activation:
-

During cephalic and gastric phases, stimulation by vagal nerve fibers


causes release of pancreatic juice.
Acidic chyme entering duodenum causes enteroendocrine cells of the
duodenal wall to release secretin, whereas fatty, protein rich chyme
induces release of cholecystokinin (CCK).
CKK and secretin enter the blood stream
Upon reaching the pancreas, CKK induces the secretion of enzyme rich
pancreatic juice, and secretin causes release of bicarbonate rich
pancreatic juice.

use examples of homeostatic imbalances (eg. pancreatitis,


malabsorptive states) to explain normal pancreatic functions in
digestive physiology

PANCREATITIS:
Causes: - defective ductal secretion of HCO3 - & H2O - significantly
decreased release pancreatic enzymes - inappropriate activation of
pancreatic enzymes - excessive alcohol intake
Symptoms: - continuous abdominal pain - weight loss - steatorrhoea
Treatment: - improve nutrition with pancreatic supplements - complete
abstention from alcohol - pain relief (aspirin, opiates)
MALABSORPTIVE STATES:
CAUSES: anything that interferes with the delivery of bile or pancreatic
juice damage of the intestinal mucosa (eg. bacterial infections)
enzyme deficiency (often genetic) anything that reduces the small
intestine absorptive surface area
Carbohydrate Malabsorption: Brush border membrane disease (usually
genetic) Example = lactase deficiency
Fat Malabsorption: Disease of liver, biliary tract (eg. gallstones), pancreas
(eg. pancreatitis)

explain the main sites in the gut for lipid, protein and carbohydrate
digestion and absorption

PRACTISE QUESTION: