Emily

& Kieran Curran Case 6 Wrap

EMILY & KIERAN CURRAN CASE

WRAP
Case 6 (Diarrhoea & Vomiting)
DIAGNOSIS: Emily – TRAVELLOR’S DIARRHOEA, Kieran –
ULCERATIVE COLITIS EXACERBATED BY TRAVELLOR’S
DIARRHOEA

University of Adelaide
MBBS I 2017
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TABLE OF CONTENTS
ANATOMY & PHYSIOLOGY .............................................................................................................. 3
1. ANATOMY OF THE GASTROINTESTINAL TRACT .................................................................................... 3
2. TRANSPORT OF MATERIALS .......................................................................................................... 22
3. FLUID MOVEMENT IN GI TRACT .................................................................................................... 23
PATHOLOGY AND PATHOPHYSIOLOGY ......................................................................................... 24
1. TYPES OF DIARRHOEA ................................................................................................................. 24
2. CHRONIC CAUSES OF DIARRHOEA .................................................................................................. 24
3. DEHYDRATION ........................................................................................................................... 27
MICROBIOLOGY AND IMMUNOLOGY ........................................................................................... 28
1. INTESTINAL FLORA ...................................................................................................................... 28
2. DEFENCE MECHANISMS ............................................................................................................... 28
3. PATHOGENS RESPONSIBLE FOR TRAVELLERS’ DIARRHOEA .................................................................. 29

CLINICAL REASONING AND CLINICAL SCIENCE ............................................................................... 30

1. MEGA MECH ............................................................................................................................. 30
2. ABDOMINAL PAIN ...................................................................................................................... 31
3. MANAGEMENT .......................................................................................................................... 32
POPULATION HEALTH AND EPIDEMIOLOGY .................................................................................. 33
1. INCIDENCE, PREVALENCE AND RISK FACTORS OF TRAVELLER’S DIARRHOEA ........................................... 33
2. PROPHYLAXIS OF TRAVELLER’S DIARRHOEA ..................................................................................... 33
3. INCIDENCE, PREVALENCE AND RISK FACTORS OF IBD ........................................................................ 33

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ANATOMY & PHYSIOLOGY

1. ANATOMY OF THE GASTROINTESTINAL TRACT

Describe the anatomy of the gastrointestinal tract, including the distribution of the lymphatic
system.
Describe the histology and absorptive function of the small intestine.
Describe the histology and absorptive function of the large intestine

4 Basic Functions of the Digestive System

Motility

• Muscular contractions that mix and move forward contents

• Smooth muscle can display action potential0induced bursts of contraction, but can also maintain
constant level of contraction (tone)
• 2 types of phasic digestive motility
o Propulsive movements propel contents forward
o Mixing movements promote digestion and exposes intestinal contents to absorbing surfaces

Secretion

• Both exocrine and endocrine secretions that consists of water, electrolytes and specific organic
constituents (enzymes, bile salts, mucus)
• Exocrine gland cells – specialized epithelial cells found in the lining of GIT and accessory organs
• Endocrine tissue – specialized epithelial cells that secrete a range of signal proteins (GI hormones or GI
peptides) à regulate digestive function

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Digestion

• Chemical break down of structurally complex foodstuffs of diet (carbohydrates, proteins, fats) into
smaller, absorbable units
o Carbohydrates: polysaccharides à monosaccharides
o Proteins: polypeptides à amino acids/small polypeptides
o Fats: triglycerides à monoglyceride
• All done by enzymatic hydrolysis which requires water

Absorption

• Small absorbable units that result from digestion, along with water, vitamins, electrolytes are
transferred from lumen into blood or lymph

Histology (4 Major Layers)

Mucosa

• Mucous membrane
• Consists of epithelium which is moistened by glandular secretions and lamina propria of areolar tissue
• Digestive epithelium
o Mostly non-keratinized stratified squamous epithelium for protection
o Simple columnar epithelium functions in secretion and absorption (stomach and intestines)
o Areas of most severe stress (mechanical stresses in oral cavity, pharynx, oesophagus) are lined
with stratified squamous epithelium
o Areas of less stress (stomach, small intestine and almost entire length of large intestine) are
lined with simple columnar epithelium containing mucous cells
o Scattered among these columnar cells are enteroendocrine cells which secrete hormones to
control activities
o Folds present called plicae which increases surface area
• Lamina propria
o Layer of areolar tissue
o Contains blood vessels, sensory nerve endings, lymphatic vessels, smooth muscle cells,
scattered lymphoid tissue and some sections have secretory cells of mucous glands

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• Muscularis mucosae
§ Contains narrow sheet of smooth muscle and elastic fibres
§ Arranged in 2 concentric layers
§ Inner layer encircles lumen (circular muscle)
§ Outer layer contain muscle cells orientated parallel to long axis of tract (longitudinal
layer)
§ This muscle layer allows for change in lumen shape and movement of epithelial pleats
and folds

Submucosa

• Layer of dense irregular connective tissue

• Binds mucosa to muscularis externa
• Contains blood vessels and lymphatic vessels and sometimes can contain exocrine glands
• Network of intrinsic nerve fibres and scattered neurons along outer margin à submucosal plexus
o Contains sensory neurons, parasympathetic ganglionic neurons and sympathetic
postganglionic fibres that innervate the mucosa and submucosa

Muscularis externa

• Smooth muscle arranged in a inner circular layer and outer longitudinal layer
• Affects movements of digestive tract and materials down tract
• Coordinated by sensory neurons, interneurons and motor neurons of enteric nervous system (ENS)
o Innervated by parasympathetic division of ANS
o Parasympathetic stimulation increases muscle tone
o Sympathetic stimulation promotes muscular inhibition and relaxation

Serosa

• Covers muscularis externa along most parts of the digestive tract

• No serosa exists at oral cavity, pharynx, oesophagus and rectum
o Network of collagen fibres called adventitia
• Also known as visceral peritoneum

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Neural Innervation of GIT

4 factors involved in regulating digestive system function:

• Autonomous smooth muscle function

• Intrinsic nerve plexuses
• Extrinsic nerves
• GI hormones

Autonomous Smooth Muscle Function

• Smooth muscle can undergo spontaneous, rhythmic cycles

of depolarization and repolarization
• Basic Electrical Rhythm (BER)
• Pacemaker cells (interstitial cells of Cajal) are located
throughout the layers of muscularis externa
• Creation of slow wave potentials (not action potentials)
which bring wavelike fluctuations in membrane potential
which bring it closer to and further away from the
threshold
• Action potentials are more likely to be triggered at the peaks of the slow-wave potential when efferent
signals sends down impulses
• Move via gap junctions
• Rate is determined by on inherent rate of pacemaker cells
• Intensity is determined by number of action potentials that occur when slow-wave potential reaches
threshold

Intrinsic Nerve Plexuses (Enteric Nervous System)

• 2 major networks
o Submucosal plexus (secretion of mucosa)
o Myentric plexus (GI motility)
• Sensory neurons (intrinsic primary afferent neurons) response to specific local stimuli in GIT (stretch,
chemoreceptors)
• Intrinsic efferent neurons innervate and control smooth muscle and exocrine and endocrine cells
• Interneurons receive synaptic input from intrinsic primary afferent neurons and modulate output of
intrinsic efferent neurons
• Excitatory interactions: acetylcholine (Ach) à contractility
• Inhibitory interactions: nitric oxide and vasoactive intestinal peptide à relaxation
• Intrinsic nerve activity can be influenced by endocrine, paracrine and extrinsic nerve signals

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Extrinsic Nerves (Autonomous Nervous System)

• Originates outside the digestive system

• Can influence motility and secretion by modifying ongoing activity in intrinsic plexuses, altering level of
GI hormone secretion or acting directly on smooth muscles and glands
• Sympathetic nerves inhibits – “fight or flight”
• Parasympathetic nerves (vagus nerve) promotes – “rest and digest”
o Part of the intrinsic nerve system via the Ach-secreting afferent neurons

GI Hormones

• Gastrin
o Secreted from G-Cells (stimulated by protein in stomach)
o Increases secretion of HCl and pepsinogen (digestion of protein)
o Enhances gastric and ileal motility, relaxes ileocecal sphincter
o Induces mass movements in colon
o Maintains well-developed, functionally viable digestive tract lining
o Inhibited by accumulation of acid in stomach and duodenum
• Secretin
o Secreted from duodenum (stimulated by presence of acid in duodenum)
o Inhibits gastric emptying
o Inhibits gastric secretion
o Stimulates pancreatic duct cells to produce large volume of aqueous NaHCO3 to neutralize acid
• CCK
o Secreted from pancreatic acinar cells (stimulated by presence of nutrients in duodenum)
o Inhibits gastric motility and secretion
o Stimulates pancreatic acinar cells to increase secretion of pancreatic enzymes
o Contraction of gallbladder and relaxation of sphincter of Oddi so bile can be emptied into
duodenum

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Peritoneum

• Layer of simple squamous epithelium with underlying supporting layer of areolar connective tissue
• Parietal peritoneum: lines wall of abdominopelvic cavity
• Visceral peritoneum: covers organs in cavity and their serosa
• 5 major peritoneal folds
o Greater omentum
§ Largest peritoneal fold
§ Drapes over transverse colon and coils of small intestine
§ From attachments along stomach and duodenum, it extends anterior to small
intestine
§ Reflects back and extends upward, attaching to transverse colon
o Falciform ligament
§ Attaches liver to anterior abdominal wall and diaphragm
o Lesser omentum
§ Suspends stomach and duodenum from liver
§ Pathway for blood vessels entering liver and contains hepatic portal vein, common
hepatic artery and common bile duct
o Mesentery
§ Binds jejunum and ileum of small intestine to posterior abdominal wall
§ Extends from posterior abdominal wall, wraps around small intestine then returns to
origin
o Mesocolon
§ Binds the transverse colon and sigmoid colon of large intestine to posterior
abdominal wall

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Oral Cavity

• Cheeks
o Externally covered by skin and internally by mucous membrane (non-keratinized stratified
squamous epithelium)
• Lips
o Fleshy folds surrounding opening of mouth
o Contraction of buccinators muscles in cheeks and orbicularis muscle in lips keeps food
between upper and lower teeth
• Oral vestibule
o Cavity bounded externally by cheeks and lips and internally by gums and teeth
• Palate
o Wall separating oral cavity from nasal cavity
o Forms roof of the mouth
o Hard palate
o Soft palate and uvula are drawn upwards and closes naropharynx during swallowing
• Tongue
o Composed of voluntarily controlled skeletal muscle
o Taste buds located on tongue
• Teeth
o Involved with mastication (chewing)
o Firmly embedded in and protrude from jawbones
o Exposed part of tooth is covered by enamel

Motility Mastication
• Mechanical break down of food by teeth
• Facilitate swallowing
• Increases food surface area on which salivary enzymes can act
• Mix food with saliva
• Expose food to taste buds (feedforward reflex à salivary, gastric, pancreatic and bile
secretion to prepare for food)

Secretion Saliva and Salivary Glands

• Secretion produced by 3 main pairs of salivary glands
o Parotid gland
o Submanidibular gland
o Sublingual gland
• Contents of saliva
o 99.5% H2O
o 0.5% electrolytes and protein
• Functions of saliva
o Digestion of dietary starches through salivary amylase
o Facilities swallowing by moistening food particles
o Antibacterial action
§ Lysozyme (destroys certain bacteria)
§ IgA antibodies
§ Lactoferrin (binds to iron bacteria require)
§ Rinses away material (possible food source for bacteria)
o Solvent for molecules that stimulate taste buds
o Aids speech by facilitating movements of lips and tongue
o Oral hygiene
o Contains bicarbonate buffers which neutralises acids in food and bacteria

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• Salivary reflex
o Saliva is continually secreted but can be increased through reflex
o In absence of food-related stimuli, low-level parasympathetic stimulation
induces basal salivary secretion
o Simple reflex
§ Stimulation of chemoreceptors and pressure receptors within oral
cavity from presence of food
§ Impulses in afferent nerve fibres carried to salivary centre in medulla
§ Salivary centre sends salivary glands to promote salivation
o Conditioned reflex
§ Occurs without oral stimulation
§ Thinking about, seeing, smelling, hearing
o Autonomic influence
§ SNS and PNS are not antagonists but rather change the quantity and
character of saliva
§ PNS à abundant flow of watery saliva rich in enzymes
§ SNS à smaller volume of thick saliva rich in mucus
Digestion Hydrolysis of polysaccharides by amylase
Absorption NONE

Pharynx

• Common passage for food, liquids and air

• Stratified squamous epithelium

Oesophagus

• Moves food from mouth to stomach during swallowing

• Transition of skeletal muscle to smooth muscle
• ~25cm
• Begins posterior to cricoid cartilage at C6
• Descends posterior to trachea
• Empties into stomach at T7
• Upper oesophageal sphincter (pharyngoesophageal sphincter)
o Is only open during swallowing to prevent air into the
stomach
o Anatomical, striated muscle sphincter
• Lower oesophageal sphincter (gastroesophageal sphincter)
o Is only open once bolus has gone through oesophagus
to prevent backward movement of gastric contents
o Physiological sphincter (acute angle, positive intra-
abdominal pressure, folds of mucosa, diaphragm)
• Histology
o Stratified squamous epithelium
o Muscosa and submucosa packed into large folds which
allow for expansion when there is a large bolus
o Submucosa contains oesophageal glands which secretes mucous to reduce friction
o Superior third of oesophagus contains skeletal muscle fibres, middle third contains a mixture
of skeletal muscle and smooth muscle, inferior third only contains smooth muscle
o No serosa but has adventitia of connective tissue

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Oesophagus
Motility Swallowing
• Oropharyngeal stage
o Initiated when bolus is voluntarily forced by tongue to rear of mouth and into
pharynx
o Afferent signals sent to swallowing centre in medulla which initiates
involuntary reflex
o Swallowing centre inhibits respiratory centre
o Uvula is elevated and seals off nasopharynx
o Tongue positioned against hard palate to keep food from re-entering mouth
o Closure of vocal cords and epiglottis to prevent bolus from entering
respiratory airways
o Pharyngeal muscles contract to force bolus into oesophagus
• Oesophageal stage
o Swallowing centre triggers primary peristaltic wave which sweeps from
beginning to end
o Progressively forward moving contractions which push bolus into relaxed area
ahead of contraction
o Secondary peristaltic wave can be initiated by stretch if food gets stuck
(mediated by intrinsic nerve plexus does not involve swallowing centre)

Secretion Mucus
• Lubricates and protects oesophagus
Digestion NONE
Absorption NONE

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Stomach

• Lesser curvature forms medial surface and greater curvature forms lateral surface
• 4 regions
o Cardia
§ Consists of superior, medial portion of stomach
§ Contains abundant mucous glands which coat connection with oesophagus and
protects tube from acid and enzymes of stomach
o Fundus
§ Superior to junction between stomach and oesophagus
§ Contacts inferior, posterior surface of diaphragm
o Body
§ Gastric glands in fundus and body secrete most of acid and enzymes involve in gastric
digestion
§ Mixing tank
o Pylorus
§ Sharp curve of J
§ Divided into
• Pyloric antrum
• Pyloric canal
§ Empties into duodenum
§ Pyloric sphincter regulates release of chyme into duodenum
• Histology
o Simple columnar epithelium lines all parts of stomach
o Secretory sheet
o Shallow depressions called gastric pits open onto gastric surface (mucosa)

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Stomach
Motility • Filling
o Interior of stomach contains folds which can flatten out as the stomach is
filled
o Vagally mediated response (receptive relaxation)
• Storage
o Pacemaker cells (interstitial cells of Cajal, ICC) generates slow-wave potentials
that sweep down length of stomach toward pyloric sphincter
o Due to the thin muscle layers in fundus and body, peristaltic contractions are
weak
o Thus, relatively quiet body allows for storage
• Mixing
o At the antrum, where muscle layers are thicker, contractions are stronger and
more vigorous
o Allows for food to mix with gastric secretions to produce chyme
o As the peristaltic contractions reach the pyloric sphincter, it closes tightly and
particles are forced back à retropulsion
• Emptying
o Factors in stomach that impact rate of emptying
§ Stomach empties at a rate proportional to volume of chyme in it
§ Stomach distension triggers increased gastric motility via
involvement of intrinsic plexuses, vagus nerves, and gastrin
o Factors in duodenum that impact rate of emptying
§ Neural response to slow gastric emptying mediated through intrinsic
plexuses (short reflex) and autonomic nerves (long reflex) à
enterogastric reflex
§ Hormonal response to slow gastric emptying involves release of
hormones known as enterogastrones from small-intestine mucosa
(secretin and cholecystokinin CCK)
§ Fat: digestion of fat takes more time than other nutrients so gastric
emptying is slow to allow small intestine enough time to digest and
absorb fat
§ Acid: Unneutralized acid may damage duodenal mucosa and
inactivate pancreatic enzymes so secretin is released to slow gastric
emptying and allow acid already there to be neutralized by sodium
bicarbonate
§ Hypertonicity: if proteins are not absorbed fast enough (due to a high
gastric emptying rate), more protein will remain in the chyme and
increase osmolarity, drawing out water

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§ Distension: too much chyme inhibits gastric emptying

Secretion Gastric glands

Cell Type Substance Stimulus Function
Secreted
Mucous Tonic secretion, Physical barrier
irritation of between lumen and
Mucous Neck Cells mucosa epithelium
Bicarbonate Secreted with Buffers gastric acid to
Exocrine

mucous prevent damage

Gastric Acid ACh, gastrin, Activates pepsinogen,
histamine kills bacteria
Parietal Cells
Intrinsic factor Complexes with Vit B
to permit absorption
Pepsinogen ACh Digests proteins
Chief Cells
Gastric lipase Acid, secretin Digests fats
Enterochromaffin- Histamine ACh, gastrin Stimulates gastric acid
like Cells secretion
Endocrine

Somatostatin Acid in stomach Inhibits gastric acid

D Cells
secretion
Gastrin ACh, peptides, Stimulates parietal
G cells
amino acids cells

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Ach= Acetylcholine

Control of gastric secretion

• Cephalic phase
o Increase secretion of HCl and pepsinogen
o Feedforward fashion in response to stimuli in head before food reaches
stomach
o Stimuli includes seeing, smelling, tasting, chewing, swallowing
• Gastric phase
o When food reaches stomach
o Stimuli such as protein, distension, caffeine, alcohol
• Intestinal phase
o Inhibitory
o Stops/slows release of gastric juices after chyme has left stomach

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Digestion • Preliminary digestion of proteins by pepsin in which complex proteins are broken down
into smaller peptides and polypeptide chains (done in the antrum)
• Some digestion of carbohydrates and lipids by salivary amylase and lingual lipase can
occur for
Absorption Only alcohol and aspirin

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Small Intestine

• Duodenum
o 25cm in length
o Closest to stomach
o Receives chyme from stomach and digestive secretions
from pancreas and liver
o Retroperitoneal position between L1 and L4
• Jejunum
o Re-enters peritoneal cavity
o ~ 2.5m in length
o Bulk of chemical digestion and nutrient absorption occurs
here
• Ileum
o Final and longest segment
o ~3.5m in length
o Ends at the ileocecal valve between ileum and cecum of large intestines
• Histology
o Plicae circulares: series of transverse folds
o Mucosa has series of finger-like projections called villi
o Simple columnar epithelium carpeted with microvilli (brush border)
o Lamina propria of each villus contains extensive network of capillaries which carry absorbed
nutrients to hepatic portal circulation

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Small Intestines
Motility Segmentation
• Oscillating, ring-like contractions of circular smooth muscle
• Churns food, mixes nutrients and digestive enzymes
• Ensure nutrients are ‘promoted’ to brush borders
• Controlled by BER (basal electrical rhythm) from ICC in muscularis externae
• Excitability of small-intestine influenced by distension, gastrin (gastroileal reflex) and
extrinsic nerve activity (done by moving starting potential which the BER oscillates
closer to or farther from threshold)
• PNS enhances segmentation, SNS depresses segmentation
Interdigestive period à migrating motor complexes
• “intestinal housekeeper activity”
• Contractions propagating from stomach through small intestine, sweeping it clear of
debris
• Cycle (3 phases)
o Phase I: 40-60 mins of relative quiet with very few contractions
o Phase II: 20-30 mins of some peristaltic contractions (varied time between
contractions)
o Phase III: 5-10 mins of intense rhythmic peristaltic contractions beginning in
upper stomach and propagating through to end of small intestine, pyloric
sphincter relaxes and opens completely
• Regulated by hormone motilin (secreted by endocrine cells in unfed state)
Ileocecal junction
• Ileocecal valve is easily pushed but is forcibly closed when cecal contents attempt to
move backward
• Smooth muscles of last section of ileum is thickened, forming a sphincter
o Usually has some tone (mild constriction)
o Pressure from cecal side causes contraction and distension from ileal side
causes relaxation
o Mediated by intrinsic plexuses
Secretion Succus entericus (1.5 L)
• Aqueous salt and mucus solution
• Secretion increases after a meal (presence of chyme)
• Mucus – protection and lubrication
• Aqueous – provides water for enzymatic digestion of food (hydrolysis)
Digestion Pancreatic enzymes and bile
• Responsible for most digestion within small-intestine lumen
• Allows for complete fat digestion, however, carbohydrate and protein digestion must
be done at the brush border
Brush border activity
• Microvilli on luminal surface of small intestine epithelia cells
• Membrane-bound enzymes:
o Enteropeptidase – activates pancreatic proteolytic enzyme trypsinogen
o Disaccharidases (maltase, sucrose-isomaltase and lactase)
o Aminopeotidases – hydrolyses small peptide fragments into amino acids
Absorption SEE TRANSPORT OF MATERIALS SECTION
Villus
• Epithelial cells cover surface of villus: joined by tight junctions, luminal brush borders,
carriers for absorption and digestion (membrane enzymes which complete
carbohydrate and protein digestion)
• Connective tissue core formed by lamina propria
• Capillary network: each villus supplied by an arteriole (+capillary network) and venule
formed which drains away
• Terminal lymphatic vessel: central lacteal occupies centre of villus core

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Pancreas (accessory)

• Mixture of following tissue

o Endocrine (no ducts): isolated islands of endocrine tissue called islets of Langerhands – insulin
and glucagon
o Exocrine (ducts): clusters of secretory cells called acini
• Exocrine pancreas
o Pancreatic enzymes secreted by acinar cells
§ Proteolytic enzymes for proteins (trypsinogen à tripsin)
§ Pancreatic amylase for carbohydrates
§ Pancreatic lipase for fats
o Aqueous alkaline solution secreted by
duct cells
§ Provides optimal conditions
for pancreatic enzymes
§ Also secreted to neutralize
acidic chyme emptied into
duodenum which could
damage duodenal mucosa
o Role of secretin and CCK in pancreatic
exocrine secretion regulation

Liver (accessory)

• Liver blood flow

o Receives 2 sources of blood
o Arterial blood from heart via hepatic
artery
o Venous blood from digestive tract via
hepatic portal vein
• Liver organization
o Function unit = lobules (hexagonal
columns of tissue surrounding central
vein)
o Each outer corner has portal triad
§ Branch of hepatic artery
§ Branch of hepatic portal vein
§ Bile duct
o Blood from hepatic arteries and hepatic
portal veins flow from periphery to central
vein through canals called sinusoids, which
contains Kupffer cells to destroy old RBCs
and bacteria
o Thin bile-carrying channel, bile canaliculus,
run between cells and hepatocytes secrete
bile which all collect and form into the
common bile duct

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• Liver secretes bile

o Opening of bile duct into duodenum is controlled by sphincter of Oddi
o When this is closed, bile is diverted back into the gallbladder, where it is stored
o Detergent action: able to convert large fat globules into lipid emulsion assisting with lipid
absorption
o Bilirubin: waste product excreted in bile
§ Yellow pigment which gives bile and faeces (brown) its colour
§ Can be reabsorbed by intestines into blood and is excreted in urine (giving it yellow
colour)
• Regulation of bile release
o Bile salts increase bile secretion (positive feedback)
o CCK release (when fat present) promotes gallbladder emptying

Large Intestines

• Involved mainly in dry and storing materials

• Cecum
o Collects and stores materials from the ileum and begins process of compaction
o Appendix (vermiform appendix) attached to cecum
• Colon
o Wall of colon forms series of pouches à haustra, which produces a series of internal folds and
allows colon to expand and elongate
o 3 separate longitudinal bands of smooth muscle (taeniae coli) run along outer surfaces of colon
o Serosa of colon contains sacs of fat called fatty appendices
o Ascending colon
§ Begins at superior border of cecum
§ Ascends along right lateral and posterior wall of peritoneal cavity to inferior surface
of liver
§ Bends sharply left at right colic flexure, marking end of ascending colon
o Transverse colon
§ Begins at right colic flexure
§ Cross abdomen from right to left
§ Supported by transverse mesocolon
o
§ Passes inferior to greater curvature of stomach and near spleen, makes a 90 turn at
the left colic flexure, marking end of transverse colon
o Descending colon
§ Proceeds inferiorly along left side until reaching iliac fossa
§ Retroperitoneal
o Sigmoid colon
§ Begins at start of sigmoid flexure
§ Empties into rectum
• Rectum
o Expandable organ for temporary storage of faeces
o Movement of faecal material into rectum triggers urge to defecate (defecation reflex)
§ Distension of rectum stimulates stretch receptors
§ Internal anal sphincter (involuntary) relaxes and rectum and sigmoid colon contract
more vigorously
§ If external anal sphincter (voluntary) is also relaxed, defecation occurs
o Exits to anal cavity through anus

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• Histology
o Lack of villi
o Abundance of mucous cells

Large Intestines
Motility Hautral contractions
• Initiated by BER of colonic smooth muscle cells and controlled mainly by locally
mediated reflexes involving intrinsic plexuses
• Oscillating ring-like contractions similar to small-intestine segmentations
• Very slow (could happen every 30 minutes)
• Non-propulsive but rather shuffles contents back and forth to maximise water and salt
absorption
Colonic migrating motor complexes
• Large propagating contractions that help propel faecal matter distally
• Fasting state
Mass movements
• Large segments of ascending and transverse colon contract simultaneously, driving
faeces 1/3 to ¼ of length of colon into distal part of large intestine
• Gastrocolic reflex triggered when food enters stomach
Secretion • Entirely protective and lubrication
• Consists of alkaline mucous solution
• No digestive enzymes
Digestion NONE
Absorption Salts and Water
• Very little absorption
+ -
• Na is actively absorbed, Cl follows passively down electrical gradient and H2O follows
osmotically

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2. TRANSPORT OF MATERIALS
Describe the function of the normal small intestinal enterocyte, including transporters on the apical
and basolateral membranes.
Material Mechanism of transport
Sodium Ions PASSIVE:
+ +
(Na ) • Occurs if electrochemical gradient favours Na
• Passive diffusion via paracellular transport between the enterocytes through
“leaky” tight junctions
ACITVE:
• Entry into the enterocyte from lumen
+
o Na channels (passive)
+ -
o Na – Cl symporter
+ +
o Na – H antiporter
+
o Na – glucose/amino acid symporter
• Exit into interstitial fluid from enterocyte
+ +
o Na – K pump
• Action of the Na/K pump that creates a concentration gradient within the
+
enterocyte, allowing entry of Na into the enterocyte
Water • Action of the Na/K pump creates an osmotic gradient and water will move from
lumen through cell into lateral space
• Results in an increased hydrostatic pressure, flushing water out of lateral space
into interior of villus
Carbohydrates • Mainly presented in forms of disaccharides maltose, sucrose and lactose
• Disaccharidases located in brush border reduce these disaccharides and
polysaccharides further into monosaccharides glucose, galactose and fructose

Glucose, • Via sodium and glucose cotransporter (SGLT) and dependent on
+
Galactose Na concentration established by Na/K pump on basolateral end
• Leaves cell via passive diffusion via glucose transporter GLUT-2
Fructose • Enters enterocytes via GLUT-5 by facilitated diffusion
• Leaves cell via GLUT-2
Protein • Presented in form of amino acids and small peptide fragments
• Amino acids absorbed by symporters
• Small peptides absorbed via tertiary active transport
+
o Na/K pump establishes concentration gradient for Na
+ + +
o Na – H antiporter pumps out H , establishing concentration gradient
+
for H
+ +
o Symporter transports H and peptide into the cell, as H must follow its
concentration gradient
Fat • Bile salt’s detergent action emulsifies large fat droplets into small droplets,
allowing greater surface area for lipase to work
• Micelles formed around monoglycerides and free fatty acids
• Monoglycerides and free fatty acids passively diffuse from micelles into
enterocytes
• In enterocyte, monoglycerides and free fatty acids are resynthesized into
triglycerides and are coated with a layer of lipoprotein à chylomicrons

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3. FLUID MOVEMENT IN GI TRACT

Account for the daily volumes of fluids ingested, secreted and absorbed and excreted from the GI
tract.
• Approximately 9.3L of fluid enters the GIT every day
o 2.3L is ingested orally through food & fluids
o 7L is secreted by the digestive tract
§ Saliva – 1L
§ Gastric juices – 2L
§ Bile – 1L
§ Pancreatic juice – 2L
§ Intestinal juice – 1L
• 9.2L of the fluid is reabsorbed into the body
o Small intestine – 8.3L
o Large intestine – 0.9L
• 0.1L of fluid is excreted in faeces

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PATHOLOGY AND PATHOPHYSIOLOGY

1. TYPES OF DIARRHOEA
Explain the mechanisms behind the different types of diarrhoea (secretory, osmotic, exudative,
reduced mucosal contact/defective mixing).
See Mega-Mech

2. CHRONIC CAUSES OF DIARRHOEA

Describe the pathology of intestinal diseases associated with diarrhoea including infections, Post-
Infectious Inflammatory Bowel Syndrome (PI-IBS), Inflammatory Bowel Disease (IBD) and Coeliac
Disease.
Explain the differences in pathology between Ulcerative Colitis and Crohn’s Disease
Irritable Bowel Syndrome (IBS)

• Underlying causes of IBS are unknown but there are certain ‘triggers’ for susceptible individuals
o Infection (gastroenteritis) à post-infectious IBS
o Food intolerance (lactose intolerance)
o Emotional stress
o Medications
• Symptoms
o Abdominal pain/cramping usually relieved by passing wind or faeces
o Alternating diarrhoea and constipation
o Sensation that bowels are not fully emptied after passing
o Abdominal bloating
o Mucous in stools
o Nausea
• Treatments (cause of IBS is unknown so can only relief symptoms)
o Dietary changes
§ Eliminating high-gas foods
§ Eliminating gluten
§ Eliminating FODMAPs
o Medications
§ Fibre supplements
§ Anti-diarrheal medications
§ Anticholinergic and antispasmodic medications
§ Antibiotics (for bacterial infections)
§ Alosetron – relaxes colon and slows movement of waste through lower bowel
§ Lubiprostone – increases fluid secretion (for IBS constipation)

Inflammatory Bowel Disease (IBD)

• Pathogenesis
o Normal immune response is triggered
o Inability to surpress immune response à chronic inflammation
o Infiltration of submucosa and activation of T Cells
o Destruction of mucosa

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• Crohn’s disease
o Inflammation in the gut lining
o Usually in the ileum or colon but can affect any part of the gut
o May be small patches of inflammation or spread along the gut
o Causes
§ Genetics
§ Immune system
§ Previous infection
§ Environmental
§ Smoking
o Symptoms
§ Vary depending on which part is inflamed
§ Recurring diarrhoea (urgency and wanting to go but with nothing to pass)
§ Abdominal pain and cramping, usually worse after eating
§ Fatigue
§ Weight loss
o Epidemiology
§ Usually starts between ages 15 and 30, and between ages 60 and 80
§ More women than men
§ Family history
st
§ More common in those who have had their appendix removed (1 5 years after)
§ More common in countries with modern western lifestyle
o Treatments
§ Aims are to treat acute flare-ups and to maintain remission
§ Salicylates
§ Corticosteroids
§ Antibiotics
§ Immunosuppressant
• Ulcerative colitis
o Inflammation usually in the rectum and colon
o Causes
§ Genetics
§ Immune system (autoimmune condition)
§ Environmental factors
o Symptoms
§ Symptoms often worse in the morning
§ Flare-ups
§ Diarrhoea with or without blood and mucus
§ Abdominal pain
§ Frequent need to go to toilet
§ Weight loss
o Epidemiology
§ Usually between ages 15 and 30
§ Affects men and women equally
§ More common in countries with modern western lifestyle
o Treatments
§ Corticosteroids + anti-inflammatory agents
§ Symptomatic treatment (antidiarrheal agents and rehydration)
§ Treating other conditions which can result from UC

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o Truelove and Witts’ Severity Index

Mild Moderate
Severe
Bowel movements (no. Fewer than 4 4–6
6 or more plus at least one of the
per day) features of systemic upset (marked
with * below)
Blood in stools No more than small Between mild Visible blood
amounts of blood and severe
Pyrexia (temperature No No Yes
greater than 37.8°C)*
Pulse rate greater than No No Yes
90 bpm*
Anaemia* No No Yes
Erythrocyte 30 or below 30 or below Above 30
sedimentation rate
(mm/hour)*
Summary

Crohn’s Disease Ulcerative Colitis

Can occur anywhere in GIT (mouth to anus) Only colon and rectum
Occurs due to unregulated immune response Occurs due to immune attack on own cells
Affects deeper layers of tissue Usually only affects mucosa/submucosa
Skip lesions interspersed between healthy tissue Continuous lesions
Tissue may take on a crater-like, cobblestone pattern Tissue becomes granular, oedematous, friable
Right lower quadrant pain or epigastric pain partly Left lower quadrant pain
relieved by defaecation
Streaked, darker blood in stools Bright blood in stools, mucus

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Coeliac Disease

• Immune system reacts abnormally to gluten, causing small bowel damage

• Villi become inflamed and flattened (villous atrophy)
• Reduction in surface area of bowel à malabsorptive symptoms
• Epidemiology
o Affects 1 in 70 Australians (80% remain undiagnosed)
st
o Genetic predisposition (1 degree relative – 10%)
• Treatment
o No cure so only way is to have a strict, lifelong gluten free diet

3. DEHYDRATION
Describe symptoms and signs related to fluid loss from diarrhoea.
See Mega-Mech

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MICROBIOLOGY AND IMMUNOLOGY

1. INTESTINAL FLORA
List the normal intestinal flora and describe their role in intestinal function.
See Defence Mechanisms

2. DEFENCE MECHANISMS
Explain the defence mechanisms against infection in the GIT.
Physical

• Mucus layer: inhibits pathogenic adhesion and invasion

• Regular sloughing of mucosal layer: removes pathogens
• Motility
o Normal function: peristalsis preventing stasis and moving pathogens through
o Abnormal: anorexia, vomiting, reactive diarrhoea to remove pathogens

Biochemical

• Acid
• Enzymes
• Chemicals (lysozymes, phospholipases, antimicrobial peptides – defensins)

Immunological

• Mucosa-associated lymphoid tissue (MALT): lymph nodes containing lymphocytes for inflammatory
defence
• Non-specific immunity
o Resident tissue phagocytes
o Neutrophils
o Macrophages
• Specific Immunity
o Secretory IgA
o Other immunoglobulins (IgM and IgG)
o T-cells and dendritic cells
o Peyer’s Patches (small masses of lymphatic tissue found in ileum region of small intestines and
monitor intestinal bacteria populations and preventing growth of pathogenic bacteria)

Microbial

• Commensal bacteria
• Functions
o Promote motility
o Help maintain mucosal integrity
o Aid immune function
o Compete with potentially pathogenic microbes for nutrients and space: by doing so, possible
pathogenic bacteria are unable to establish themselves in the intestine and cause harm
o Help digest food and make nutritional contributions: bacteria can produce enzymes that can
break down dietary fibre that human enzymes cannot break down, allowing absorption of
nutrients that would otherwise be lost

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3. PATHOGENS RESPONSIBLE FOR TRAVELLERS’ DIARRHOEA

List the main pathogens responsible for Travellers’ diarrhoea and describe the:
1. routes of infection
2. timelines from infection to symptoms/signs
3. symptoms and /or signs which can distinguish types of pathogens
Class Pathogen Route IP SP Symptoms Mechanism
Water Diarrhea
3-4 Releases Heat Liable (LT) Toxin which causes the
FB/WB 1-3 Stomach Cramps
Days activation of Cl- channels (CFTR) and inhibition of apical
ETEC (Raw Meat/ Days Nausea (w/wo
(7) Na/Cl- transport overall causing efflux of water into
Veg/Milk) Vomiting)
lumen.
FO Fever
Stomach Cramps EHEC produces Shiga (or Shiga-like) toxin. Enterocyte
FB/WB 3-4
5-7 Bloody Diarrhea uptake of the toxin causes cessation of protein
EHEC (Raw Meat/ Days
Days Vomiting synthesis and subsequent death of enterocytes. Death
Veg/Milk) (1-10)
Fever (<38.5˚C) of cells and lesions result in bloody diarrhea
FO
Diarrhea (may be
blood) Salmonella enter M-Cells (GALT) by endocytosis leading
FB/WB 12-36
Stomach Cramps to inflammation and diarrhea. Additionally they disrupt
Salmonella (Raw Meat/ Hours 4-7 Days
Nausea (w/wo tight junctions between cells resulting in unregulated
Veg/Milk) (6-72)
Vomiting) flux of ions/water/immune cells
Fever
Diarrhea (may be
FB/WB
bloody and painful) Bacteria infect the colon and cause inflammation and
B Shigella
(Raw Meat/
1-2 Days 5-7 Days Fever death of colonic cells. Some strains release the Shiga
Veg/Milk)
Nausea/Vomiting toxin, and hence has similar effects to EHEC.
Flatulence
Diarrhea (frequent C.Jejuni are able to travel through the host using their
FB/WB and flagellae and colonize the SI (mainly). There is
Campylobacter (Raw Meat/ bloody/mucosal) subsequent adhesion and invasion of enterocytes. The
2-4 Days 7 Days
jejuni Veg/Milk) Abdominal Pain bacteria release Cytolethal distending toxin (Cdt) which
Fever causes apoptosis. Hence damage and inflammation of
Nausea/Vomiting tissue results in bloody diarrhea).
Watery Diarrhea
Clostridium Fever Infection of bowel followed by release of enterotoxin and
FO <7 Days
difficile Loss of Appetite cytotoxin which produce inflammation and diarrhea
Abdominal Pain
V.Cholerae colonises the intestine and causes an
Watery Diarrhea increase in cAMP which activates Cl- transporters
V. Cholerae WB/FB 2-3 Days 3-6 Days Vomiting (CFTR) on the apical surface of crypt cells and inhibits
Leg Cramps Na+/Cl- co-transport at the villus cells resulting in
secretory diarrhea
Rotavirus causes malabsorption due to destruction of
Watery Diarrhea
enterocytes. Furthermore, the toxic rotavirus protein
Nausea
Rotavirus FO 2 Days 3-8 Days NSP4 activates Ca2+ dependent Cl- transporters in the
Vomiting
apical membrane, causing efflux of Cl- and hence efflux
Low Fever
of water into lumen.
Noroviris colonizes the jejunum, and causes damage to
Watery Diarrhea the villi as well as causing enzymatic dysfunction and
V Norovirus
FO 12-48
1-3 Days
Nausea damage to tight junctions. This leads to malabsorption
FB/WB Hours Vomiting and anion secretion, resulting in water flux into the
Low Fever lumen. Vomiting results from virally mediated changes
to gastric emptying and motility.

Astroviruses infect enteric cells and cause cell death by

3-10 1-2 Diarrhea
Adenovirus FO inhibiting protein synthesis. This leads to inflammation
Days Weeks Fever
and subsequent diarrhea.

Trophozoites (a stage in the life cycle) enter the SI and

Diarrhea induce a number of effects on the villi. They cause villus
Steatorrhea flattening. Giardia attack enterocytes and tight junctions
FO 1-3 2-6
P Giardia
WB/FB Weeks Weeks
Flatulence through protease action, causing epithelial damage and
Stomach Cramps increased permeability of the SI. In addition, they
Nausea mediate apoptosis in enterocytes. Overall they lead to
malabsorption and hence diarrhea.

Thanks to Teham Ahmad

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CLINICAL
REASONING AND
CLINICAL
SCIENCE
1. MEGA
MECH
Explain the
mechanisms of the
symptoms and signs
in these patients.
Explain the
mechanisms of
production of
diarrhoea for each of
these patients.

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2. ABDOMINAL PAIN
Explain the mechanisms of production and referral of pain from the intestines and the distribution of
the referred pain.
Parietal peritoneum

• Receives same somatic nerve supply as the region of abdominal wall that it lines
• pain is well localised and is sensitive to pressure, pain, laceration and temperature

Visceral peritoneum

• Receives same nerve supply as the viscera it invests

• pain is poorly localised and is only sensitive to stretch and chemical irritation
• Pain is referred to areas of skin (dermatomes) which are supplied by same sensory ganglia and spinal
cord segments as nerve fibres innervating viscera
o Pain from foregut structures are referred to epigastric region (T5-T9)
o Pain from midgut structures are referred to umbilical region (T10-T11)
o Pain from hindgut structures are referred to pubic region (T12-L1)

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3. MANAGEMENT
Describe the management of a patient with persistent diarrhoea after returning from travel in areas
which carry high risk for Travellers’ diarrhoea (management refers to investigations, advice and
medications where prescribed and follow -up).
Investigations

• Coeliac serology
o Measures antibody levels in blood which are typically elevated with untreated coeliac disease
• Faecal calprotectin
o Substance that is released in intestines in excess when there is inflammation
• Blood tests
o Complete blood count
o Hb
o MCV
o WCC
o ESR (erythrocyte sedimentation rate)
o Iron, ferritin
o Folate
o Vit B12
o Calcium
o Electrolytes
o Thyroid function
o Liver function testing
• Antibody tests
o Total IgA
• Stool tests
o Microscopy for parasites
o Culture for bacteria
• Endoscopy (looking side body using an endoscope)
o Proctosigmoidoscopy (examination of large intestine from rectum to sigmoid colon)
o Colonoscopy (examination of entire colon)
• Radiology
o Abdominal X-ray
o Small bowel enema (injection of liquid/gas into rectum to allow X-ray imaging)
o Small bowel barium follow through (ingestion of enteric contrast (barium) and fluoroscopies
are done

Medications

• Antibiotics will help with bacterial causes of Traveller’s Diarrhoea

• Dosage for adults only
o Ciprofloxacin: 500mg twice daily for 1 day (if no improvement, can be used for 3 days)
o Azithromycin: 500-1000mg for 1 day or 500mg once daily for 3 days
o Rifaximin: 200mg three times daily for 3 days

Follow-up

• Oral rehydration therapy

• Food: avoid fatty foods, spicy foods or dairy while recovery
• If persists or a fever occurs, or if blood becomes present immediately seek medical care

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POPULATION HEALTH AND EPIDEMIOLOGY

1. INCIDENCE, PREVALENCE AND RISK FACTORS OF TRAVELLER’S DIARRHOEA

Demonstrate knowledge of the incidence and prevalence of Travellers’ Diarrhoea and the locations
where risk is highest.
Identify the risk factors for contracting Travellers’ Diarrhoea.
Incidence

• >60% may experience it

Prevalence

Risk Factors

• Age <30 years

• Adventurous travel
• Unhygienic primitive environment
• Reduced gastric acidity (i.e., resulting from
histamine H2 blocker or proton pump inhibitor
therapy)
• Immunodeficiency disorder
• Prior (> 6 months previously) residence in an
undeveloped country

2. PROPHYLAXIS OF TRAVELLER’S DIARRHOEA

Explain the measures advised for prophylaxis (prevention) of Travellers’ Diarrhoea and how they can
break down in practice.
• Proper sewage treatment and water disinfection
• Do not drink tap water
• No ice in beverages
• No eating salads or other forms of raw vegetables
• No eating fruits that cannot or is not peeled on the spot
• Boil water for 3-5 minutes
• Drug prophylaxis
o Bismuth subsalicylate (Pepto-Bismol), two 262-mg chewable tablets four times daily, taken
with meals and once in the evening
o Ciprofloxin (Cipro), 500 mg once daily
o Norfloxacin (Noroxin), 400 mg once daily
o Ofloxacin (Floxin), 300 mg once daily
o Doxycycline (Vibramycin), 100 mg once daily
o Trimethoprim-sulfamethoxazole (Bactrim DS), 160 mg/800 mg once daily

3. INCIDENCE, PREVALENCE AND RISK FACTORS OF IBD

Demonstrate knowledge of the incidence, prevalence, and risk factors associated with Inflammatory
Bowel Disease.
See Chronic Causes of Diarrhoea

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