GIT MODULE

1st MBBS Repeat Campaign - 2019

26TH BATCH – 2015/2016

Faculty of Medical Sciences – University of Sri Jayewardenepura
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1st MBBS Repeat Campaign – 26th Batch

Saliva
constituents of saliva
Regulation
• Secretion is under neural control
Inorganic Organic • Parasympathetic impulses plays a major rule.
Na , K , Cl-, HCO3-,
+ +
Agglutinogens • Sympathetic input slightly modifies the composition of saliva
PO4-, Ca, P Gamma globulins [ increase the proteinaceous content ] , has little influence on the volume.
Salivary Proteins • Secretion is prompted by
Lysozymes - act of chewing
- nausea
• It is hypotonic compared to plasma - input from higher centres [ prompted by
• alkaline Important in neutralizing any gastric secretions that reflux - thinking, seeing or smelling food
into the oesophagus. conditioned response ]
• pH - - inhibited by fear and during sleep
• Daily secretion – 1 to 1.5 l per day
• Salivary glands consist of acini which produce the primary
secretion. When salivary secretion is initiated surrounding blood vessels dilate smell Pressure
and the composition of saliva is modified as it flows from acini into ducts. taste Higher Salivatory nucleus in the
sight Centers of medulla mouth
Blood vessel Duct sound
Superior Salivatory Inferior Salivatory
Na+ & Cl- nucleus nucleus

K+ & HCO3 -
Facial Nerve Glossopharyngeal Nerve

Ducts are relatively impermeable to water loss of NaCl renders saliva

hypotonic particularly at low
Submandibular ganglion Otic ganglion
secretion

When rate of secretion Increases less time for NaCl to be extracted Submandibular gland Parotid gland

But always stays hypotonic relative to plasma Tonicity of saliva Increase salivary secretion via effects on
acinar secretion , vasodilatation
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1st MBBS Repeat Campaign – 26th Batch

Functions of saliva
Deglutition
• Facilitates swallowing 3 phases
• Moisturizes the mouth 1. Oral phase
• Serves as a solvent for molecules that stimulate taste buds. 2. Pharyngeal phase
• Aids speech 3. Oesophageal phase
• Cleanses the mouth
• Initiate digestion [ salivary amylase initiate starch digestion ] Oral phase
• Protects the oral cavity by bacteria • Voluntary
• Buffering action by HCO3- & PO43- [maintain oral pH at about 7 ] • Food bolus is formed by muscles of mastication, tongue and by lips and
cheeks.
Xerostomia • Bolus is propelled towards the oropharynx by the backward and upward
• Deficient salivation pressure of the tongue against the hard palate.
• Have a higher than normal incidence of dental caries due to lack of
antibacterial action. Pharyngeal phase
• Involuntary
Food bolus enters the posterior mouth and pharynx

Stimulates epithelial swallowing receptor areas , especially on the tonsillar pillars

Afferents pass via trigeminal, glossopharyngeal and vagus nerves

to the NTS and nucleus ambiguus in the medulla oblongata

Efferents via facial, trigeminal and hypoglossal nerves

To the pharyngeal musculature and the tongue

Initiates a series of automatic pharyngeal muscles contractions

• Soft palate is pulled upwards

- prevent regurgitation of food into the nasopharynx
• Palatopharyngeal folds are pulled medially
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1st MBBS Repeat Campaign – 26th Batch

• Vocal folds are approximated , larynx moves upwards and Oesophagus

anteriorly, epiglottis swings down. Lower oesophageal sphincter
- prevent food from entering the airways • Tonically active
• Relaxes on swallowing
➢ Respiration is inhibited for 1-2 seconds – deglutition apnea • Tonic activity between meals prevent reflux of gastric contents into the
➢ Swallowing center inhibits the respiratory center oesophagus
➢ Peristaltic contractions of the pharynx pushes the bolus into • Made up of 3 components
the oesophagus 1. Oesophageal smooth muscle – intrinsic sphincter
2. Fibers of the right crus of the diaphgram – extrinsic sphincter
3. Oblique/sling fibers of the stomach
Oesophageal phase
Factors preventing gastro-oesophageal reflux
• Cricopharyngeal muscle relaxes : Relaxation of the upper
oesophageal sphincter 1. Acute angle between the stomach and the oesophagus
Pharyngo-oesophageal junction 2. Intra abdominal part of the oesophagus – when there’s positive intra
relaxes. abdominal pressure , walls of this portion is compressed.
Bolus enter the oesophagus 3. Mucosal rosette – folds of mucosa at the junction aid in occluding the
• Vocal cords open lumen
• Resumption of rhythmic breathing 4. Right crus of the diaphragm – exerts a pinchcock – like action
5. Oblique fibers of the stomach wall – create a flap valve

Tone of the LOS

• Under neural control

Stimulation of vagus Release of NO & VIP from

interneurons innervated
by other vagal fibers

Release Ach

Contraction of the Relaxation

intrinsic sphincter
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1st MBBS Repeat Campaign – 26th Batch

Crura – Innervated by phrenic nerves Due to back pressure

Contraction is coordinated with respiration and contractions of
chest and abdominal muscles. Difficulty in swallowing

➢ Thus the intrinsic and extrinsic sphincters operate together to permit orderly Dysphagia
flow of food into the stomach and prevent reflux into the oesophagus.

Factors influencing LOS pressure Gastro Oesophageal Reflux Disease (GORD)

Increase Decrease • GORD is a chronic relapsing condition in which the reflux of stomach
contents into the oesophagus and beyond provokes symptoms and/or
Gastrin CCK, Secretin, Progesterone
Acetylcholine Atrophine complications.
Protein meal Alcohol, Chocolate
Histamine, antacids Caffeine, Smoking, Pregnancy Causes :
• Motor abnormalities
- impaired LOS resting tone
- Transient LOS relaxation
Clinicals
• Impaired oesophageal acid clearance and delayed gastric emptying
Achalasia(Failure to relax)
• Visceral hypersensitivity
• Impaired mucosal resistance
• This occurs due to incomplete myenteric plexus of oesophagus
• Anatomical factors
Deficiency of myenteric plexus at the LOS
- hiatal hernia
✓ Reflux occurs when LOS pressure < 6mmHg/ Pressure in the stomach
Increased resting LOS tone Release of NO & VIP defective
exceeds LOS pressure
✓ Acidity of gastric contents and the amount of time in contact with
oesophageal mucosa is related to the degree of mucosal damage.
Incomplete relaxation on swallowing

Symptoms : Regurgitation
Food accumulates in the oesophagus
Heart burn
Organ becomes massively dilated
Nausea
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1st MBBS Repeat Campaign – 26th Batch

Management : Gastrointestinal Regulation

• Life style changes
- Head of bed raised 6-8 inches • The various functions of the GIT (secretion, digestion, absorption and
- Do not lie down for 3 to 4 hours after eating motility) must be regulated in an integrated way to ensure efficient
- Smoking cessation assimilation of nutrients after a meal.
- Reduce alcohol consumption There are 3 main modalities for regulation.
• Pharmacological 1. Endocrine regulation
- Antacids 2. Paracrine regulation
- H2 receptor blockers 3. Neural regulation
- Proton pump inhibitors
• Surgery Endocrine/Paracrine regulation

Hormone Site of secretion Function Regulation

Complications : Ulcers
Strictures Gastrin G cells in the antral • Stimulation of Secretion :
portion of the gastric acid and Luminal : Peptides
Barrett’s – carcinoma of oesophagus
stomach pepsin secretion & amino acids,
Cough and asthma • Trophic action on distention
Inflammation of throat and larynx the mucosa of Blood-borne : Ca ,
Aspiration pneumonia stomach, small Epinephrine
intestine and large Neural : Increased
intestine vagal discharge via
• Stimulate insulin GRP
secretion
Secretion :
Luminal : acids,
somatostatin
Blood-borne :
Secretin,GIP, VIP,
Glucagon,
Calcitonin
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1st MBBS Repeat Campaign – 26th Batch

CCK I cells in the mucosa • Stimulation of Products of duodenum & • Stimulates post
of upper small pancreatic digestion: petides jejunum prandial insulin
intestine enzyme secretion and amino acids secretion
Nerves in the distal • contraction of the FAs containing
ileum and colon gall bladder more than 10 C
• Relaxation of atoms VIP Neurons in the GIT • Stimulates
sphincter of oddi intestinal
• Augments the secretion of
action of secretin electrolytes and
• Inhibits gastric hence of water
emptying • Relaxation of
• Trophic effect on intestinal smooth
the pancreas muscles
• Enhance the (sphincters
motility of small included)
intestine & colon • Peripheral
• Increase the vasodilatation
synthesis of • Inhibit gastric acid
enterokinases secretion
• Potentiates the
action of Ach in
salivary glands
Secretin S cells in the mucosa • Increase HCO3- Products of protein
of upper small secretion by digestion Motilin Enterochromaffin • Contraction of
intestine pancreas and Acid in the upper cells (ECL) and Mo smooth muscles in
biliary tract small intestine cells in the stomach, the stomach and
small intestine and
• Augments the intestine in the
colon period between
action of CCK
• Decrease gastric meals.
acid secretion
• Contraction of the
• Inhibits the Acid in the lumen
pyloric sphincter
Somatostatin D cells in the secretion of
pancreatic islets and gastrin, VIP, GIP,
• Inhibit gastric
GIP K cells in the Glucose and fat in D cells in GI mucosa motilin, secretin
secretion and
mucosa of the the duodenum • Inhibits pancreatic
motility
exocrine secretion
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1st MBBS Repeat Campaign – 26th Batch

• Inhibits gastric Neural regulation

acid secretion and
motility Nervous system of the GIT
• Inhibits
gallbladder Extrinsic innervation Intrinsic innervation
contraction
• Inhibits
Autonomic nervous system Enteric nervous system
absorption of
glucose,a.a , TAGs
Parasympathetic Myenteric plexus
- vagal and sacral efferents - innervates longitudinal &
Gherlin Stomach • Stimulate growth - Increase intestinal smooth circular smooth muscle
hormone muscle activity layers
secretion - concerned primarily with
motor control
Sympathetic
Submucous plexus
- T5 to L2
- Decrease smooth muscle - innervates the glandular
activity cause sphincters to epithelium, intestinal
contract endocrine cells and
submucosal blood vessels
- involved in the control of
intestinal secretion
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1st MBBS Repeat Campaign – 26th Batch

General patterns of motility Types of peristalsis

Peristalsis
• It is a reflex response initiated when the gut wall is stretched by the contents of 1. Primary
the lumen. • Begins as food bolus enters the oesophagus
• Occurs from the oesophagus to the rectum. • 3-4 cm/s
• Propel the contents forward at rates that vary from 2 to 25cm/s. • Pass to the stomach in about 8-10 seconds
• Peristaltic activity can be increased or decreased by the autonomic input to the • When in the upright position liquids and semisolid food
gut. generally fall by gravity to the lower oesophagus ahead of the
peristaltic wave
Food bolus 2. Secondary
• When primary wave is weak or absent to sweep out the
Local stretching of gut wall remaining
food.
Release serotonin • Distention caused by the remaining food initiates this.

Activates sensory neurons It is therefore possible to swallow food while standing on

one’s head.
Activate myenteric plexus

Cholinergic neurons of myenteric plexus

Segmentation and mixing

that pass in a retrograde direction
activate neurons that release
Substance P and Ach
that pass in an anterograde direction
activate neurons that secrete
NO & VIP
• Segmentation is a motility pattern that is produced when the meal is
present.
• This retard the movement of the intestinal contents along the length
of the intestinal tract to provide time for digestion and absorption.
• Provides for ample mixing of chyme with digestive juices.

Cause smooth muscle contraction Relaxation ahead of the

behind the bolus food bolus

1st MBBS Repeat Campaign – 26th Batch
Segment of bowel contracts at both ends
2nd contraction occurs in the center of the segment
Force the chyme both backward and forward
Mixing pattern persists for as long as nutrients remain in the lumen
to be absorbed
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Basic Electrical Rhythm
• Smooth muscle of the GIT has spontaneous rhythmic fluctuations in
membrane potential (between -65mv to -45mv) except in the oesophagus
and the proximal portion of the stomach.
• It is initiated by the intestinal cells of Cajal.
• This rarely causes muscle contraction.
• ‘Spike potentials’ superimposed on the most depolarizing portions of the
BER waves increase muscle tension.
• Depolarizing portion is due to Ca2+ influx and repolarizing portion is due to
K+ efflux.
• Neurotransmitters and polypeptides affect the BER
- Acetylcholine : Increase the no. of spikes and the tension of smooth
muscle
- Epinephrine : Decrease the no. of spikes and the tension
• Rate of BER varies throughout the GIT
eg: Stomach – 4/min
Duodenum – 12/min
• Function of BER is to coordinate peristaltic and other motor activity
eg: Set the rhythm of segmentation
Contraction can occur only during the depolarizing part of the
waves
• After vagotomy/transection of the stomach wall, peristalsis in the stomach
become irregular and chaotic.
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1st MBBS Repeat Campaign – 26th Batch

Stomach
• Most distensible organ
• Function :
Storage of food
Chemical and mechanical breakdown of food
Formation of chyme from the churning action
Absorption of water, drugs and alcohol
Secretion of gastric acid and intrinsic factor
Digestion of proteins
Release of food in a controlled steady rate

Gastric mucosa contains many deep glands

In the ,
Cardia and pyloric region – Glands secrete mucous
Body and fundus – Glands also contain
Migrating Motor Complex
Parietal/ Oxyntic cells – secrete HCL & intrinsic factor
Chief/Zymogen/Peptic cells – secrete pepsinogen and
• Occurs during fasting between periods of digestion. gastric lipase
• Cycles of motor activity migrate from the stomach to the distal ileum.
• Contractions migrate aborally at intervals of 100 min. at a rate of 5cm/min. Constituents of gastric juice
• MMC is initiated by motilin • Cations – Na+, K+, Mg2+, H+
• Anions – Cl-, HPO4-, SO42-
• During each MMC gastric secretion , bile flow and pancreatic secretion increases
• Pepsins
which serve to clear the stomach and small intestine of luminal contents in
• Lipase
preparation for the next meal. • Mucous
• Intrinsic Factor

Gastric Mucosal Barrier

Composed of
• Thick mucous layer – secreted by the neck mucous cells &
by the mucous cells on the epithelial surface between glands.

• HCO3- - trapped in the mucous gel formed by glycoprotein.

Does the buffering action of H+ near the surface of gastric
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1st MBBS Repeat Campaign – 26th Batch

mucosa. GRP released from enteric nerve Presence of oligopeptides in the

• Tight junctions between cells – prevent penetration of enzymes and acids into endings gastric lumen
the cells.
• Trefoil peptides – secreted by mucosa. Acid resistant. Stabilize the mucous ,
HCO3- layer. Gastrin released by G cells in the antrum

➢ Components : maintain a pH gradient between the lumen and the cell.

Prevent auto digestion. Binds to CCK-B receptors on Binds to CCK-B receptors on ECL
Prevents irritation by gastric juice. Parietal cells cells
Provide protection against bacteria. Chief cells

➢ Substances which disrupt the barrier :

Vinegar Activate secretion Release Histamine
Ethanol
Bile salts
Aspirin and other NSAIDs Inhibit prostaglandin synthesis Binds to H2 receptors on parietal cells

Prostaglandin - Increase mucosal blood flow

Stimulus for HCO3- and mucous secretion Stimulate secretion

Gastric juice secretion mechanism

➢ Parietal & Chief cells can also be stimulated by Ach released from enteric
nerve endings in the fundus.

Action on parietal cells

• Cells are packed with mitochondria that supply energy to drive the apical H+,
K+ ATPase that moves H+ out of the cell against a concentration gradient.

• At rest the proton pumps are sequestered within the cell in a series of
membrane compartments – tubulovesicles
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1st MBBS Repeat Campaign – 26th Batch

➢ Therapeutic significance Secretion can be markedly inhibited by blocking

the action of only one of the triggers. (most common – H2 antagonists)

Gastrin Ach Histamine

GI Secretion Phase

1. Cephalic phase
CCK-B M3 H2 2. Gastric phase
3. Intestinal phase

Elevate cytosolic free Ca2+ levels Increases intracellular cAMP Cephalic phase

Sight, smell, thought of food

Translocate tubulovesicles to the apical membrane

Brainstem dorsal vagal complex

Fuse with invaginations of the membrane canaliculi

Vagal outflow to the stomach

Amplify the apical membrane area, position the proton pumps to begin
acid secretion
Release GRP & Ach

• Vagotomy abolishes the response.

• Amount of secretion is limited. Responsible for 1/3 – ½ of acid secreted
➢ Secretion of H+ is accompanied by the release of equivalent numbers of during a normal meal.
HCO3- into the bloodstream. This is later used to neutralize gastric acidity.

➔ The 2 distinct pathways for activation (Ca2+, cAMP) are synergistic.

➢ Greater than additive effect on secretion rates when histamine + gastrin or

histamine + Ach or all 3 are present simultaneously.

➢ Physiological significance High rates of secretion can be stimulated with

relatively small changes in availability of each of the stimuli.
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1st MBBS Repeat Campaign – 26th Batch

Gastric phase

Meal constituents(oligopeptides) Presence of food

Intestinal phase
Chyme enters the intestine
Stimulates gastrin secretion
Distention of the stomach
Fat , Glucose , Acid
Gastric juice secretion
Activate stretch receptors
Stimulate GIP secretion Stimulate secretin secretion Stimulate
(Protein digestion products somatostatin
Provoke a vago- Local reflexes also stimulate this) secretion
vagal reflex (Submucous plexus)

Inhibits gastric
Ach , GRP secretion motility decrease gastric acid Inhibits both
secretion G and ECL cells as well
Further amplification of gastric juice parietal cells
secretion

➢ Presence of meal buffers gastric acidity.

Otherwise,

H+ increases Release somatostatin Post alkaline diet

After diet

inhibit secretion of
Increase gastric acid secretion

G cells ECL cells Parietal cells

Increase removal of HCO3- from parietal cells

Gastrin Histamine Gastric juice

Add them to venous blood
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1st MBBS Repeat Campaign – 26th Batch

Blood pH α [HCO3-]
pCO2 ◆ Alteration in gastric mucosa

Usage of CO2 is high to produce H2CO3 in the parietal cell Treatment:

• There can be spontaneous healing of the ulcer. If not may undergo lifestyle
changes , and stop NSAIDs, reduce alcohol , stress and stop smoking.
Level of HCO3- in the blood increases • If it’s a bacterial infection, antibiotics can be given for the eradication of
bacteria.

Remaining CO2 in the venous blood is less than that of arterial blood ➢ other
Proton pump inhibitors – omeprazole
H2 receptor antagonists – cimetidine
Raise the pH Leads to post alkaline tide Synthetic analogue of prostaglandin – misoprostol

Clinicals

Peptic Ulcer disease Dumping syndrome

• It is a condition in which there’s breakdown of the gastric mucosal barrier and • Dumping syndrome can occur as a result of partial or total gastrectomy.
penetration of mucosa up to the muscle layer. (If it is a superficial inflammation
of mucosal layer it is called gastritis) Therefore after ingestion , food directly enters into the small intestine

• Acid causes irritation

• Pepsin causes autodigestion Increased osmotically active particles Rapid gastric emptying
in the small intestine
Causes:

◆ Prolong exposure to acidic pH (presence of gastrinomas , zollinger Intra luminal fluid sequestration Rapid glucose absorption
ellison syndrome)

◆ Helicobacter pylori bacteria – The bacteria has an enzyme urease which Decrease ECF Bloating Rapid hyperglycemia
hydrolyzes urea to NH3 and CO2 . This helps the bacterium to survive in volume
the acidic environment of the stomach. NH3 mediate tissue inflammation
and injury.
Hypovolemia Abdominal pain Increased insulin secretion
◆ Frequent use of aspirin and other NSAIDs.
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1st MBBS Repeat Campaign – 26th Batch

Prolong hypoglycemia Gastric emptying

Hypotension • During fasting between periods of digestion, migrating motor complexes
Diarrhoea pass along the stomach. These are called hunger contractions.
Increase catecholamine • Function of this is to sweep out the remnants of foods.
Reduced secretion from adrenal medulla
baroreceptor Proximal stomach (fundus & upper 2/3 of the body)– electrically silent
discharge

Sympathetic activation When bolus enters the stomach

Sympathetic activation

Fundus & upper portion of the body relax

Tachycardia
Faintish
Sweating Accommodate the food with little if any increase in pressure

Early dumping syndrome Late dumping syndrome Receptive relaxation

• Receptive relaxation is vagally mediated and triggered by movement

Effects of gastrectomy other than dumping syndrome : of the pharynx and oesophagus.
• Intrinsic reflexes also leads to relaxation as the stomach wall is
1) Billouse vomiting – due to loss of action of pyloric sphincter and LOS. stretched.
• This increases dispensability , ensures storing of food and reduce
2) Diarrhea – due to rapid transit of large volume of osmotically active particles
intra gastrial pressure.
into the small intestine.

3) Small stomach syndrome – premature sensation of fullness

Peristaltic waves controlled by the gastric BER begin from the body towards
the distal stomach
4) Anaemia - Due to Fe(Fe2+ to Fe3+ by HCL) and Vitamin B12 deficiency

As it pass towards the antrum the waves become more intense. Become powerful
constrictor rings.

Constrictor rings play a role in mixing the contents

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1st MBBS Repeat Campaign – 26th Batch

Vomiting
Contraction ring propagate from the mid to distal antrum
• Forceful expulsion of contents of the stomach and upper small intestine
through the mouth.
Peristaltic wave reach the pylorus
• A protective mechanism that exist in order to eliminate toxins from the
body.
Food material is trapped against the occluded pylorus
➢ There are several factors that lead to vomiting.

Chyme is pushed back to the gastric lumen – retropulsion grinding

Due to this the particle size decreases
Neural factors Chemical factors Psychic factors

Due to irritation of an Drugs – morphine, Disgusting smells,

After such contractions pylorus opens
organ. chemotherapy sights
GIT – gastritis, peptic
ulcer, pancreatitis Alcohol Anxiety
Emptying of chyme to the duodenum
Outside GIT – Metabolic disturbances as Extreme pain MI,
Factors affecting gastric emptying
Labyrinthitis, Increased acidosis, uremia, ureteric colic
intracranial pressure hyperammonemia
Gastric Duodenal Hormonal

1. Amount of food Duodenal receptors sense CCK, Secretin – Inhibits

Distention osmolality, acidity, stretch emptying Areas in the brain involved in vomiting

GIP – Inhibits motility • Reflex is mediated by vomiting center in the medulla.

Local myenteric plexus & enterogastric reflex
gastrin reduce emptying • Chemoreceptor trigger zone in the area postrema also initiates
vomiting through circulating chemical agents.
Increase motility
• NTS contributes to emetic cascade following vagal activation. It
2. Type of food receives input from area postrema , vagus & from labyrinths.
CHO> Protein>Fat
Fastest Slowest ✓ Nausea is an unpleasant experience prior to vomiting. It is associated
with decreased gastric motility and increased tone in the small intestine.
This results in signal to the salivary glands to increase secretion with pallor,
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1st MBBS Repeat Campaign – 26th Batch

sweating etc. Efferents:

• Cranial nerves 5,7,9,10,12 – to the upper GI tract

✓ Retching is spasmodic respiratory movements conducted with a closed • Spinal nerves – diaphragm and abdominal muscles
glottis. • Autonomic nerves – lower GI tract

Neural pathways of vomiting

Events in vomiting

Programmed Pain • Reverse peristalsis empties material from the upper part of the small
Pharyngeal vomiting Sights intestine into the stomach.
Stimulation response Anticipation • Breath is held in mid inspiration.
• Hyoid bone and larynx is raised to pull the upper oesophageal sphincter
open.
Diencephalon • Closure of glottis by downward movement of epiglottis.
Limbic system • Lifting of the soft palate to close the posterior nares.
• Contraction of the diaphragm along with simultaneous contraction of
abdominal wall muscles.
Nucleus brainstem
• Squeeze the stomach between the diaphragm and the abdominal
Tractus Solitarius vomiting center
muscles.
• Build intra gastric pressure to a high level.
• Relaxation of LOS and expulsion of stomach contents into the
oesophagus.
Vagus Nerve Area Postrema Cerebellum
Chemoreceptor
trigger zone
Autonomic response in vomiting
Labyrinth
• Sympathetic response : Sweating, pallor, increased respiration and heart
rate and dilatation of pupils.
Gastric mucosa Drugs
eg: opioids, chemotherapy • Parasympathetic response : Profuse salivation, pronounced motility of the
Hormones Motion oesophagus, stomach and duodenum, relaxation of oesophageal sphincters
eg: pregnancy (hCG) Vertigo
Ipecac
Cytotoxic drugs
Irritants
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1st MBBS Repeat Campaign – 26th Batch

Consequences of severe vomiting Functions of the small intestine.

• Dehydration 1. Provides the body with continuous supply of water, electrolytes, vitamins
• Metabolic alkalosis and nutrients.
• Hypokalaemia • This is achieved through,
• Hypochloraemia I. Mechanical functions.
II. Secretory functions.
Principles of management
III. Digestion and absorption.
• Treatment of the cause of vomiting
2. Other functions
• Replenish the fluid and electrolyte loss – ORS, normal saline
I. Defense mechanism – immunology
• Antiemetics
II. Regulatory functions.

Receptors that trigger vomiting Mechanical functions

• 5-HT3 receptors Three types of smooth muscle contractions in fed state.

Through serotonin released from ECL cells in the small intestine. I. Peristalsis
Acts via area postrema and NTS. II. Segmentation contractions
III. Tonic contractions
• Dopamine (D2) receptors
In area postrema and NTS. Migrating motor complex sweep the chyme remaining in the S.I during fasting.

Major classes of antiemetics • Peristalsis propels the chyme towards the large intestine
• Segmentation contractions and the tonic contractions increase the transit
• 5-HT3 antagonist – ondansetron time in the small intestine.
• D2 antagonists – chlorpromazine, haloperidol o Here a segment of bowel contracts at both ends and the second
contraction occurs at the center.
o Unlike peristalsis it forces chyme both backwards and forwards.
o And provides ample mixing of intestinal contents with digestive juices.

1st MBBS Repeat Campaign – 26th Batch
Secretory functions
1) Active transport of chloride ions in to the lumen.
• Cl⁻ transported across the basolateral membrane in to the enterocyte via
Na⁺/K⁺/2Cl⁻ cotransporter.
• Cl⁻ enter the lumen via the cystic fibrosis conductance regulator (CFTR) channel
which is activated through CAMP pathway.
• With the entry of Cl⁻ into lumen, water and sodium follow passively via tight
junctions to maintain neutrality.
2) Bicarbonate secretion into small intestine.
• Prominent in the proximal duodenum as a defense mechanism for acidic gastric
juice.
• Secreted by both Cl⁻/HCO₃⁻ exchanger and also CFTR in the apical membrane.
• In the enterocyte bicarbonate for secretion is either generated by the activity of
carbonic anhydrase, or taken up by bloodstream via the sodium bicarbonate
cotransporter.
3) Mucus secretion
• Mucus secretion is caused by surface epithelial cells, Brunner’s glands and goblet
cells.
• The secreted mucin is hydrated and forms a blanket of mucus that lubricates,
binds bacteria and holds immunoglobulin in place.
• Contains HCO₃⁻ which helps to protect he mucosa from gastric acid.
Digestion/Absorption
Absorption by the small intestine
• The portion of the intestinal cell exposed to the lumen is called apical
membrane.
• Sides and base of the cell make up basolateral membrane.
• Tight junctions seal adjacent epithelial cells.
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There are two routes by which molecules make their way from intestinal lumen to
Bloodstream.
• The paracellular route
o Transport across tight junctions between enterocytes.
o Impermeable to large organic molecules.
• The transcellular route
o Transport across the plasma membrane of enterocyte.
o Transported from apical to basolateral membrane by the transporters
located on those membranes.
o Water is absorbed passively
o Nutrients like glucose/amino acids absorbed actively
Digestion and absorption of nutrients
CHO
• Mainly occurs with the pancreatic amylase and brush border enzymes.
• Broken down into oligosaccharides, disaccharides, maltose and alpha limit
dextrins.
• Further digestion of starch derivatives occur in intestinal cells by isomaltase,
maltase, sucrase, lactase.
• Secondary active transport of Na⁺ causes absorption of glucose via the
sodium dependent glucose transporter. (SGLT-1).
• GLUT-2 transporter is responsible for glucose transport out of the gut
epithelial cells into the interstitium and then to the capillaries.
Proteins
• Breakdown continues in the small bowel by activated pancreatic enzymes
including trypsin, chymotrypsin, elastase and small intestinal peptidases
(aminopeptidase and dipeptidase).
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1st MBBS Repeat Campaign – 26th Batch

• Presence of bacterial and viral proteins activate them and they secrete IgA
Fat in response to subsequent exposure to the same antigen.
• Fats get emulsified in the small intestine by the detergent action of bile acids.
• Bile acids lipids and bile salts interact spontaneously to form micelles.
Pathological conditions
• After forming micelles digestion take place by the action of pancreatic lipase.
a. Ileal resection.
Water absorption • Malabsorption of vitamin B₁₂ cause megaloblastic anemia.
• Occur in two ways • Malabsorption of bile salts, reduced micellar formation and malabsorption
fatty acids cause steatorrhea.
I. Nutrient dependent water absorption • Bile salts, fatty acids, interfere water and electrolyte absorption and it leads
to diarrhea.
Ex: Nutrient dependent water absorption coupled with Na⁺ and glucose via secondary
active transport. Presence of glucose in the intestinal lumen facilitates the reabsorption
b. Gall stones
of Na⁺. Thus, improves the water absorption.
II. Water absorption independent of nutrient uptake
c. Oxalate stones
• Dietary oxalates precipitate as calcium oxalates.

Vitamins d. Mechanical obstruction of S.I

• Fat soluble vitamins (A, D, E, K) are ingested as esters and digested by cholesterol • Localized mechanical obstruction.
esterase prior to absorption. • The segment proximal to the point of obstruction dilates and fills with
• Most vitamins are absorbed in upper small intestine except vitamin B₁₂ which is fluid and gas.
absorbed in ileum after binding with intrinsic factor. • Pressure in the segment rises and the blood vessels in the wall of
intestine are compressed (local ischemia).
Ca⁺⁺ • Results in sweating, severe vomiting, dehydration, metabolic alkalosis
• Absorption is stimulated by 1, 25-dihydroxycholecalciferol (vitamin D₃). etc.
• Inhibited by phosphates and oxalates. • If not relieved fatal.

e. Paralytic ileus
• Most of the iron absorption occur in duodenum. • Intestinal motility is decreased.
• To relieve, NG suction (aspirate gas and fluid)

GIT immune system

• Intestinal mucosa contains lymphocytes and inflammatory cells to defend the
mucosa if epithelial defenses are breached.
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1st MBBS Repeat Campaign – 26th Batch

Large Intestine

Principal Functions

1. Absorption of water and electrolytes from the chyme and form solid
Feces.
2. Secretory function (Cl-, K+ and mucus)
3. Chemical digestion
4. Storage of fecal matter until it can be expelled.

Fluid Absorption
Colonic contents are isotonic. There are 2 mechanisms for water
absorption.
I. Electroneural mechanism
II. Electrogenic mechanism

Electroneural mechanism

Na+ and Cl- are absorbed from the lumen through electroneural mechanism by the
coupled activity of Electrogenic mechanism

• Sodium/hydrogen exchanger (NHE) • Mainly in the distal colon

• chloride/bicarbonate exchanger in the apical membrane
Water then follows to maintain an osmotic balance.
• Sodium enter via an ENaC (epithelial sodium channel)
• This ensures minimal loss of water via feces.
• If digested particles are unabsorbed the osmolality in the lumen will be
hypertonic and water will passively drain into the colonic lumen.
• Saline cathartics (magnesium sulphate) can be used as a laxative as it is
poorly absorbed.
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1st MBBS Repeat Campaign – 26th Batch

Secretory function

Cl- secretion

Occurs continuously throughout the colon.

‘

Secretion of mucus

• Epithelial cells in the colon secrete mucus with HCO3-.

Chemical digestion

No enzymes are secreted. Bacteria ferment

K+ secretion • Undigested CHO into carbon dioxide and methane gas.

• Undigested proteins into indoles (gives off bad odor)
• Secreted into the lumen with mucus via K+ channels in luminal & basolateral • bilirubin into stercobilinogen
membrane.
• In addition K+ moves passively down its electrochemical gradient. Colonic movements
• K+ is removed by the H+/K+ ATPase pump in the luminal membrane in the distal
colon. 1. Segmentation – ring like contractions of the circular muscle divide the
colon into pockets called haustra.
2. Peristaltic waves
3. Mass action movements – occurs only in the colon and occurs about 10
4. times per day.
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1st MBBS Repeat Campaign – 26th Batch

• There is an intrinsic reflex mediated by enteric nervous system which is

Defecation relatively weak to cause effective defecation.

• It is a spinal reflex which can be be voluntarily inhibited or facilitated.

• The urge to defecate first occurs when rectal pressure increases to about 18
Anal sphincters mmHg

Internal sphincter External sphincter • When the pressure reaches 55 mmHg , the external as well as the internal
sphincter relaxes and there is reflex expulsion of the contents of the rectum.
Involuntary Voluntary
Sympathetic – excitatory Pudendal nerve ◆ Voluntary defecation can be initiated by straining even before critical
Parasympathetic – inhibitory pressure is reached which relaxes the external sphincter.

Feces enters the rectum. Distention of the rectum ◆ Usually the anorectal angle is 90° and contraction of puborectalis muscle
inhibits defecation

Stretch receptors in the rectal wall
Sensory fibers terminating at S2-S4 spinal segments
Sacral segment (S2-S4) of the spinal cord
But with straining in voluntary defecation
• Abdominal muscles contract
• Pelvic floor lowers and outwardly moves
This leads to : Relaxation of puborectalis muscle and reduction of anorectal
angle (to 15° or less) and relaxation of external anal
sphincter

Gastroileal Reflex
Pelvic splanchnic nerves
When the food leaves the stomach, the caecum relaxes and the passage of
chyme through the ileocaecal valve increases. This is a vagovagal reflex.
Smooth muscles of descending & sigmoid colon and rectum

Gastrocolic Reflex
Peristaltic waves
Distention of the stomach by food initiates contraction of the rectum leading
to a desire to defecate.
Relaxation of internal anal sphincter It is amplified by the action of gastrin on the colon.
So defecation after meals is the rule in children.
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1st MBBS Repeat Campaign – 26th Batch

Constipation Diarrhoea
• It is defined as having two or more of the following for at least 12 weeks :
Infrequent passage of stools, straining > 25% of time, • Imbalance in secretion and absorption at any level of the GIT can result in
passage of hard stools, incomplete evacuation and diarrhoea.
sensation of anorectal blockage.
Clinical presentation : Increased stool frequency
Increased stool volume
Clinicals Decrease in stool consistency

Megacolon (Hirschsprung’s diesease) Diarrhoea can be acute (less than 2 weeks duration ) or chronic (over 4 weeks)

Cause : Absent/ deficiency of ganglion cells in the myenteric plexus in Types of diarrhoea
sigmoid colon.

So neither defecation reflexes nor strong peristaltic movements occur in *Secretory *Osmotic Motility Inflammatory
this area of the colon.

Results in over distention of the colon. Secretory

• Secretion increases
• Absorption is usually
• No/ little structural change
• Does not stop with fasting

Secretagogues – substances that stimulate fluid and electrolyte secretion in

both health and diseases.

Blood-borne Intraluminal
VIP Exotoxins from direct ingestion
Serotonin Enterotoxins
E.coli , cholera
Bile acids
Fatty acids
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1st MBBS Repeat Campaign – 26th Batch

Osmotic
Secretory diarrhoea in vibrio cholera infection
• Due to malabsorbed nutrients
• Caused by : • Cholera bacillus stays in the intestinal lumen . It secretes a toxin that can
lactase deficiency bind to and enter intestinal epithelial cells.
glucose, galactose or fructose malabsorption
mannitol, sorbitol ingestion Cholera bacillus
some salts (MgSO4)
Pancreatic enzyme inactivation (by excess acid) Produce a toxin
Defective fat solubilization
Enter enterocyte of the gut wall

Motility disorder Binds adenosine diphosphate ribose to the α subunit of Gs

Due to increased motility of the gut Inhibits its GTPase activity(Prevent hydrolysis of GTP to GDP therefore G protein
remain at the activated state)

Rapid movement of food through intestine Prolonged stimulation of adenylyl cyclase

Marked increase in the intracellular cAMP

Not enough time to absorb particles
cAMP dependent Cl- channels remain open : Increased Cl- secretion
eg: hyperthyroidism
Vagotomy In addition function of the mucosal NHE transporter for Na+ is reduced

Inflammatory exudation Na+ absorption is reduced

inflammation to the mucosal lining of the brush border Large amounts of osmotically active particles remain in the lumen

Drag water into the lumen

Reduced ability to absorb nutrients and cause passive loss of protein rich fluid
Results in profuse diarrhoea
eg: Inflammatory bowel disease
Infection (shigellosis) Na+,K+ ATPase and the Na+/glucose co-transporter are unaffected , so coupled
reabsorption of glucose and Na+ bypass the defect.
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1st MBBS Repeat Campaign – 26th Batch

Liver

Functions of the liver

Osmotic diarrhoea in lactose intolerance 1. Formation and secretion of bile.

• Individuals suffering from this condition cannot fully digest the dietary 2. Nutrient metabolism.
dissacharide lactose
- carbohydrate metabolism
• When dairy products are ingested , the lactose can remain in the lumen in • conversion of galactose and fructose to glucose
quantities sufficient to pull water from the bloodstream by osmosis and • Gluconeogenesis – occurs to a significant extent only when the
thus causing diarrhea [glucose] falls below normal
• Glucose buffer function – remove excess glucose from blood,
store it and then return it to the blood when blood [glucose]
begins to fall to low.

- Protein metabolism
• Deamination of amino acids

- Fat metabolism
• Fatty acid oxidation
• Synthesis of cholesterol, phospholipids and most lipoproteins.

3. Storage of substances
- Storage of fat soluble vitamins and vitamin B12
- Iron as ferritin
- Glycogen

4. Inactivation of substances
- Toxins
- Hormones
Steroids
Sex hormones

5. Detoxification of substances
- Ammonia : Urea cycle leads to formation of urea.
- drugs : structurally altered , produces less lipophilic
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1st MBBS Repeat Campaign – 26th Batch

metabolites that are biologically inactive Cellular adaptations

6. Synthesis of plasma proteins • Many mitochondria – to facilitate energy production as well as urea
production
90% of the plasma proteins are formed in the liver (except • Cells with prominent nucleus and large nucleolus – protein synthesis
immunoglobulins) • Large number of RER and free ribosomes
• Abundant golgi apparatus and secretory vesicles
- albumin - Proteins in fibrinolytic system • Lot of lysosomes – important for detoxification
- clotting factors - Acute phase proteins
- angiotensinogen - antithrombin 3 Implications of deranged liver functions

7. Immunity Liver failure

Kupffer cells : very efficient phagocytic activity
removal of bacteria , defective RBC and Acute liver failure Chronic liver failure
foreign particles.
-Occurs over a short period of time -Occurs over a long period of
time

Functional adaptations of the liver Due to : hepatitis Due to : alcohol

toxins
• High flow, low pressure, low resistance system drugs

F= P Results in : Hepatic encephalopathy Results in: Hepatic encephalopathy

R Coagulopathy Coagulopathy
Jaundice Jaundice
High flow : 28% of cardiac output and has a dual blood supply. Portal hypertension
2/3 from portal vein , 1/3 from hepatic artery Ascites

Low pressure : In the sinusoids pressure gradient of 5-10 mmHg

Large fenestrations in the endothelium.
Lack of basement membrane.
Low resistance : low resistance circulation
average transient time 8.4s
Hepatic encephalopathy
• A reversible neuropsychiatric disorder due to failure of the liver
to detoxify toxins.
• May complicate acute/chronic liver failure

- Gut derived toxins include NH3 , mercaptans , aromatic amino

acids
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1st MBBS Repeat Campaign – 26th Batch

• In liver failure clotting factors synthesis is impaired thus cloooting

➢ Normally all the NH3 in the body is ultimately funneled to the liver which mechanism gets impaired resulting in coagulopathy.
detoxifies it by converting it to urea by the urea cycle which can be excreted by
the kidney.
Jaundice
➢ This results not only from the functional hepatocytes, but also from shunting of
portal blood around the liver. • Yellowish discolouration of skin, sclera and mucous membrane due to
accumulation of bilirubin in subcutaneous tissue.
Due to porto-systemic shunts
• Normal plasma bilirubin level - < 1mg/dl
NH3 bypass the liver • If its > 3.5 mg/dl , it is called jaundice

Enter the systemic circulation • In liver failure this results due to decreased uptake of unconjugated
bilirubin into the liver as well as due to decreased conjugation. *

NH3 is freely permeable so it crosses the blood brain barrier

Portal hypertension

Affects a number of neurotransmitter systems • It is defined by a portal venous pressure gradient greater than 5mmHg.
- Increased cerebral glutamine
- Increased cerebral glutamate • Occurs due to a rise in intrahepatic vascular resistance.

Cirrhotic liver loses the physiologic characteristics of a low P circuit for blood
Increased glutamine in astrocytes increases osmotic stress flow.
-Causes cellular swelling - Loss of endothelial fenestrations
-Altered neural astrocyte interaction - Increased fibrogenesis
-Decreased synaptic transmission

Increased blood pressure within the simusoids

Hepatic encephalopathy Transmitted to the portal vein

Coagulopathy
Portal hypertension
• Clotting mechanism involves the extrinsic and intrinsic pathways.
Portal vein lacks valves : Increased P transmitted back to other vascular
beds
• Except for factors VIII and IV all the clotting factors are syntesized in the liver.
resulting in – Splenomegaly
Oesophageal varices
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1st MBBS Repeat Campaign – 26th Batch

Ascites

• Ascites is defined as the accumulation of fluid in the

peritoneal cavity exceeding the normal maximum volume of
25ml.

• Factors associated with ascites in chronic liver failure,

- Portal hypertension
- Low serum albumin
- sodium and water retention

Exocrine Pancreas

Contains both ENDOCRINE and EXOCRINE tissue.

Exocrine Component

• Major bulk of the pancreas.

• Includes ductal and acinar cells.
• Ductal cell : Bicarbonate secretion Composition of Pancreatic Juice
• Acinar cell : Pancreatic enzyme
Volume is about 1500 ml per day in a healthy adult.

1. Digestive Enzymes
I. Pancreatic amylase – Carbohydrate digestion
II. Trypsin, Chymotrypsin, Elastase, Carboxypeptidase – Protein
digestion
III. Lipase – Lipid digestion
IV. Ribonuclease, Deoxyribonuclease – Nucleic acid digestion
2. HCO3- - Neutralize gastric HCL
3. NaCl & H2O
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1st MBBS Repeat Campaign – 26th Batch

Pancreatic Juice Pancreatic Enzyme – Lipid and CHO Digestion

• It’s secreted most abundantly in response to the presence of chime in the upper Enzyme Activator Substrates Products
potions of the small intestine.
• The characteristics of the pancreatic juice is determined by the types of
stimulation and types of food in the chyme.

Functions of exocrine pancreas

1) Storage and secretion of multiple enzymes for digesting of all three major types
of food (proteins, CHO, fats)
2) Contains large quantities of HCO- for neutralizing the acidity of the chyme
emptied from the stomach into the duodenum.
(The pancreatic juice is alkaline (pH around 8) due to high HCO3– content).
3) Secretion of proteolytic enzyme inhibitor (trypsin inhibitor)

Pancreatic enzymes PROTEIN DIGESTION in SMALL INTESTINE

When first synthesized in the pancreatic cells, the proteolytic digestive enzymes are in
the inactive forms ( trypsinogen, chymotrypsinogen, and procarboxypolypeptidase)
They become activated only after they are secreted into the intestinal tract to prevent
autodigestion of pancreas.
• pH of the intestinal contents in the duodenal bulb is 3.0–4.0, but in the
rest of the duodenum it is about 6.5.
• Proteolytic enzymes of the pancreas and intestinal mucosa such as trypsin,
chymotrypsins, and elastase act at interior peptide bonds are called
endopeptidases.

• The formation of the active endopeptidases from their inactive precursors

occurs only when they have reached their site of action
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1st MBBS Repeat Campaign – 26th Batch

• The activation occurs through the formation of the active endopeptidases from
their inactive precursors through

– action of the brush border hydrolase, Enterokinase

– action of trypsin

• So once some trypsin is formed there is an auto-catalytic chain reaction.

Trypsin inhibitor

Secretion of trypsin inhibitor prevents digestion of the pancreas itself.

If proteolytic enzymes juice become activated before they secret into the
intestine trypsin and the other enzymes activated would digest the pancreas
itself.

Pancreatic Enzyme – Protein Digestion The same cells that secrete proteolytic enzymes of the pancreas secrete
simultaneously another substance called trypsin inhibitor.

It prevents activation of trypsin in the pancreas.

Enzyme Activator Substrates Products
As it is the trypsin that activates the other pancreatic proteolytic enzymes, trypsin
inhibitor prevents activation of the others as well.

Autodigestion of Pancreas
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1st MBBS Repeat Campaign – 26th Batch

When the pancreas becomes severely damaged or when a duct becomes blocked, After heavy drinking
large quantities of pancreatic enzymes are accumulated in the pancreas.

The effect of trypsin inhibitor is not sufficient to prevent activation of trypsinogen.

So the activation of trypsin will lead to activation of other proteolytic enzymes and
Acytaldehyde
damage (digest) pancreatic tissue within a few hours, giving rise to the condition
called acute pancreatitis.

Inflammation of Direst toxic effect on acinar cells

Acute Pancreatitis Sphincter of Oddi
Acute inflammation, damage cause fibrosis and loss of function.

Common causes are Gall stones & Heavy use of Alcohol. Retention of Pancreatic

Enzymes in ducts and acini

Signs and symptoms of acute pancreatitis

Upper abdominal pain Trypsin inhibitor cannot prevent Activate trypsin

Nausea the activation of trypsinogen
Vomiting

Fever Activate all other proteolytic enzymes (chymotrypsin,

Laboratory finding of Serum pancreatic amylase and lipase help to differentiate this phosphorylase A2, elastase )
condition from other diseases.

Acute Pancreatitis associated with biliary tract disease

Lodged gallstone at the ampulla of Vater Reflux duodenal content to the pancreatic
duct Digest pancreatic tissues within few hours

Bacterial toxins/ free bile acids
cause inflammation.
tract via lymphatics from gallbladder to pancreas
Acute Pancreatitis
Alcohol
Pathogenesis of Acute Pancreatitis
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1st MBBS Repeat Campaign – 26th Batch

• Chronic pancreatitis is a progressive disorder leading to both exocrine and

endocrine pancreatic insufficiency.
Activated enzymes destruct proteins and lipids of blood vessels, tissues, and cell
membranes leading to oedema, necrosis, heamorrhagic, coagulation and inflammation. • In chronic pancreatitis, there is chronic inflammation of the parenchyma,
leading to progressive destruction of the acini, stenosis, dilation of
• Trypsin activate killikrein-kinin system vasodilation, increase vascular
pancreatic ductules & fibrosis of the gland over a long period.
permeability oedema, inflammation, coagulation
• Eventually, there is impairment of the gland's exocrine functions and
• Pancreatic Lipase damage pancreatic acinar cells and surrounding adipose sometimes of its endocrine functions as well.
tissue fat necrosis
• Common cause is alcohol consumption. Other causes are nutritional
insufficiency, trauma, idiopathic.

• Activated proteases digests elastin in blood vessel walls Damage or destruction of exocrine potion results – maldigestion syndrome
vascular injury hemorrhage hemorrhagic pancratitis In CHO and protein digestion, deficiency of pancreatic enzymes can be compensated
by enzymes of gastric and other intestinal secretion but pancreatic lipase is essential
• Activated Phospholipase A2 liberate phospholipids which will be converted to for fat digestion, its absence leads to steatorrhea.
arachidonic acid and form prostaglandin, leukotrines and lead to coagulation
and inflammation ischemia and infarction due to coagulation
• Steatorrhea
Complications – Jaundice, Hypocalcemia
Disorders interfering with normal pancreatic enzyme activity cause mal-digestion
Pancreatic Lipase digest fat of pancreas release large amounts of of fat leading to steatorrhea (fatty stools).

retroperitoneal fat free fatty acids – Production of voluminous or bulky, foul-smelling, greasy, frothy,
pale yellow, and floating stools due to maldigestion/abosorption
Mesenteric fat of fat.

(pancreatic, billiary, hepatic or even gastric cause can lead to steatorrhea)

2+
Parathyroid gland unable to Ca form soaps with FFA Voluminous or bulky is due to accumulation of unabsorbed of hydroxylated fatty
respond quickly and prevent its absorption acids (cathartic action).These fatty acids inhibit the absorption of sodium and water
and increase the bulk of the stool.

Steatorrhea can be diagnosed by placing the patient on a high-fat diet (50–150 g/d),
Hypocalcemic tetany collecting all stools for 3 days, and determining the average daily fecal fat excretion.
A value of more than 7 g of fat per day is abnormal.
Chronic Pancreatitis
Reasons for Steatorrhea in Pancreatic Insufficiency.
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1st MBBS Repeat Campaign – 26th Batch

1) inadequate delivery of digestive enzymes deliver to the duodenum in chronic

pancreatic insufficiency
Nephrolithiasis
I. pancreatic lipase is essential for fat digestion
• B12 insufficiency
II. Although pancreatic amylase and trypsin are important for carbohydrate and
protein digestion, other enzymes in gastric and intestinal juice can usually Vitamin B12 – R complex cannot be absorbed and prevent B12 being digested before
compensate for their loss. it enters to the ileum.

2) Absence of pancreatic bicarbonate secretion produced acidity in the intestine due to In a normal person,
acidic chime and this will lead to
Pancreatic protease degrade R factor free B12 (and get bound to IF)
I. Inhibition of the activity of pancreatic lipase
Absorbed at ileum
II. Reduced bile activity in acidic media on fat digestion/absorption. This is due
In pancreatic insufficiency,
to
Pancreatic protease levels are low B12 – R complex remains
i. Bile salt will be precipitated in the intestine

ii. So reduced reuptake of bile salts resulting deficiency of bile salts

B12 insufficiency – megaloblastic Free B12 levels decrease
iii. This in turn causes failure of micelle formation and interference with
fat absorption. anaemia & cannot be absorbed

• Weight loss
• Hypocalcaemia
Long term malabsorbance Protein catabolism
Due to maldigestion of fat absorption of fat soluble vitamins decrease
Loss of appetite Muscle Wasting
Ca2+ remains in the gut Vitamin D decrease
Nausea

• Nephrolithiasis Acute Pancreatitis Chronic Pancreatitis

Oedema Steatorrhea
As Ca2+ forms soaps with FFA Ca2+ oxalate formation decreases
Fat Necrosis, hemorrhage, Hypocalcaemia
coagulation Nephrolithiasis
Jaudice Megaloblastic Anemia
Oxalates remain in solution and get Hypocalcaemic tetany Weight loss
Resulting hyperoxaluria absorbed at the colon
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1st MBBS Repeat Campaign – 26th Batch

• Gastric phase - in response to distension of the stomach

Regulation of secretion

1) Neural regulation
Intestinal Phase
Acetylcholine, released from the parasympathetic vagus nerve endings /enteric nervous
system After chyme leaves the stomach and enters the small intestine, pancreatic secretion
becomes copious, mainly in response to the hormone secretin.
2) Hormonal regulation
Cholecystokinin When chyme is emptied to the duodenum
secreted by duodenal and upper jejunal mucosa in response to food (fat and amino The acidity of HCL Presence of food in the duodenum
acids)

Secretin
Secretin in S cells in the mucosa Especially the presence of proteoses
secreted by the duodenal and jejunal mucosa when highly acid food enters the small duodenum and jejunum and peptones and long-chain fatty acids
intestine

• Secretion of pancreatic juice is primarily under hormonal control.

secrete large quantities of fluid Enzyme rich pancreatic secretion
There are 3 phases of pancreatic secretion.
containing a high concentration
• cephalic phase of HCO3- but a low concentration
• gastric phase of Cl-
• intestinal phase

Cephalic and Gastric Phases

• Due to acetylcholine release by the vagal nerve endings. Acetylcholine acts

acinar cells mediated via Phospholipase C.

• Enzyme rich secretions

• Secretions are in small quantities

• Cephalic phase - stimulated by behavioural cues related to the sight and smell of
food