Learning Objectives

Main objectives:
GASTROINTESTINAL Review basic physiology
DISORDERS Learn pathophysiology
Recognize clinical application

Lecture Objectives
Introduction to common symptoms & signs of
pathophysiological relevance e.g. dysphagia, Common Symptoms
vomiting, diarrhoea
Difficulty in swallowing (dysphagia)
Learn clinico-pathologic correlations of some
Vomiting (emesis)
common gastrointestinal disorders e.g.
gastroesophageal reflux disease, peptic ulcer Diarrhoea
disease, malabsorption
For each condition, students are expected to
revise the basic physiology, learn
pathophysiology, recognize clinical relevance,
appreciate the application in patient care

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 Swallowing (Deglutition)
Transit of food from mouth, to
Dysphagia the pharynx, down
Expected to learn: esophagus to stomach
Definition: difficulty in swallowing Transfer of food to pharynx is
voluntary, thereafter under
Review swallowing mechanism &
reflex control
swallowing reflex
Swallowing reflex
Disorders related to swallowing: causes of
dysphagia and diagnosis

Movement of Food through Esophagus

Swallowing Reflex
Material moves from regions of higher intraluminal pressure
Initiated by stimulation of to regions of lower pressure Berne, Levy et al. Physiology Ch 31

pressure receptors around

the opening of the pharynx
by food
Afferent signals reach
swallowing centre in medulla
oblongata & lower pons
Send efferent ordered and
coordinated motor signals to
muscles in pharynx, larynx,
esophagus & respiratory
muscles for swallowing
Guyton & Hall, Textbook of Physiology Ch 63

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Dysphagia
Definition: difficulty in swallowing
Causes of dysphagia
Functional disorders
Obstructive disorders: due to pathological
changes in the esophagus and oropharynx
Dysphagia: Functional disorder
Functional disorders
Esophageal
Disorder in neuromuscular transmission
e.g. myasthenia gravis
Muscle disorder
e.g. muscle dystrophy
Motility disorder
e.g. diffuse esophageal spasm
achalasia
(Due to damage of myenteric plexus in
lower third of esophagus; receptive
relaxation of lower sphincter is lost)
Dysphagia: Functional disorder
Functional disorders
Pre-esophageal:
Neural causes
e.g. damage of swallowing centre e.g. by
stroke
poliomyelities()
Infection of bulbar motor neurons by poliovirus
causing paralysis of swallowing muscles
Damage in nerves involved in swallowing
Dysphagia: Obstructive disorder
Obstructive pathological changes in esophagus
External obstruction:
e.g. goitre , enlarged lymph nodes
Mediastinal tumor
Internal obstruction
Cancer of esophagus
Esophageal stricture or chronic inflammation
related to GERD or hiatus hernia
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 Dysphagia Vomiting (Emesis)
Diagnosis of Dysphagia Expected to learn:
Differentiate functional from obstructive causes Definition of vomiting
Obstructive disorders usually manifest with difficulty Learn vomiting reflex, emetic stimuli
in swallowing solid food; e.g. progressive dysphagia Complications of vomiting and physiological
in esophageal cancer basis
Functional disorders usually manifest with difficulty
Treatment of vomiting
in swallowing both solid and liquid food
Manometric measurement
Find out cause with endoscopy

What causes vomiting?

Vomiting (Emesis) (Emetic stimuli)

Vomiting is the forceful expulsion of gastric

(duodenal) contents from the gastrointestinal
tract via the mouth
Vomiting has protective value: removal of
toxic ingested substance before they are
absorbed
Nausea may be associated with vomiting:
may condition the individual to avoid future
ingestion of foods containing the toxic
substances

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 Vomiting Reflex Complications of Vomiting
Emetic stimuli 1. Dehydration from fluid loss, may cause circulatory
Afferent: vagal & sympathetic problems due to loss of plasma volume
Chemoreceptor Trigger zone: floor 2. Electrolyte imbalance
of 4th ventricle near area postrema
Vomiting centre in medulla, near 3. Acid-base imbalance
tractus solitarius at level of dorsal 4. Aspiration & pneumonia
motor nucleus of the vagus nerve
Efferent through V, VII, IX, X, XII 5. Tears in the mucosa at the junction of stomach &
to upper GIT & spinal nerves to esophagus (Mallory-Weiss tear) for repeated,
diaphragm & abdominal muscles severe vomiting
Guyton& Hall Textbook of Physiology Fig 66.2

Vomiting: Electrolyte & Acid-Base Imbalance Treatment of Vomiting

Gastric juice contains HCl; Gastric vomiting Treatment
leads hypochloremic metabolic alkalosis and Find out the cause of vomiting
often hypokalemia
(The hypokalemia is an indirect result of the kidney Treat the underlying causes
compensating for the loss of acid) Treat complications of vomiting
Anti-emetics if needed
A less frequent occurrence results from a
vomiting of intestinal contents, including bile
salts and HCO3- which can lead to metabolic
acidosis.

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 Diarrhea Diarrhea
Expected to learn: Definition:
Definition of diarrhoea, acute vs chronic Increased frequency of stools, usually
accompanied by increased volume and
Review GI fluid balance decreased consistency of feaces
Pathophysiological mechanisms of diarrhoea Increase daily stool weight >200g in adults
Know common causes of acute and chronic
diarrhoea Diarrhea can be:
Complications of acute diarrhoea acute (<3-4 weeks) or
Management of acute diarrhoea: oral chronic (> 1 month)
rehydration therapy

Normal GI Fluid Movement Causes of Diarrhea

Daily GI fluid intake &
secretions Cause: Basic pathophysiological mechanisms
Absorption of fluid &
electrolytes by intestine Absorption < Secretion
Water absorption is a
passive process following
active electrolyte transport, Causative mechanisms:
especially Na+ Decreased GI fluid absorption
Secretion by crypt cells
Under normal conditions, Decreased time for GI fluid absorption
Vander Human Physiology Ch 15
Absorption > Secretion, Increased secretion by crypt cells
resulting in net absorption
(about 99% of fluid load is
reabsorbed, only 1% excreted in
feces)

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 Causes of Diarrhea
1. Impaired absorption by small or large intestine
Inflammatory disease e.g. Crohns disease
Mucosal damage e.g. coelic disease, radiation
enteritis
Infection with enterotoxic pathogens
2. Secretory diarrhoea
e.g. enterotoxins from vibrio cholerae
or E. coli
Polypeptide hormone tumors
Acute Diarrhea
Mostly due to bacterial or viral infection
Death from diarrhea was the leading cause
of infant mortality in the developing world
until oral rehydration therapy was introduced
Diarrhoea is now the second leading cause
of mortality for children under 5, accounting
for 17% of all deaths, second only to
pneumonia at 19%
How does acute diarrhea cause death?
Causes of Diarrhea
3. Osmotic diarrhoea
Presence of unreabsorbable, osmotic solutes in
gut lumen
e.g. Lactase deficiency
4. Accelerated transit through intestine, thereby
limiting the time available for absorption
e.g. Irritable bowel syndrome
Different mechanisms may coexist in a single patient
Acute Diarrhea in Gastroenteritis
Pathophysiological mechanisms:
Infection with enteropathogenic bacteria destroy mucosa
and reduced fluid absorption
Stimulated mucosal secretion
e.g. enterotoxins from vibrio cholerae stimulates
production of cAMP & increased chloride secretion resulting in
massive diarrhea that can be life threatening
Increased motility, thus reducing time available for fluid
absorption
Diarrhoea helps to rid the body of toxic substances, should we
stop the diarrhea?
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 Consequences of Diarrhoea Consequences of Diarrhoea

1. Acute diarrhea causes dehydration Electrolyte & acid-base disturbances

From mild to severe dehydration Hypokalaemia
Severe dehydration may cause circulatory shock Secretion of K+ in secretory diarrhoea, villus
adenoma
Volume contraction Aldosterone renal
2. Acute diarrhea causes electrolyte & acid-base K+ secretion
disturbances
Hyperchloremic acidosis
Secretion of HCO3- metabolic acidosis
Death can result from circulatory shock +/- electrolyte
and acid-base imbalance Secretion of HCO3- coupled to absorption of Cl-
hyperchloremia
Either no change in plasma Na+, hypernatremia or
3. Chronic diarrhoea may lead to malnutrition hyponatremia, depending on the relative loss of
Na+ and water & fluid replacement

Death from Diarrhoea Treatment of Acute Diarrhoea

Death from diarrhea was the leading cause of
infant mortality in the developing world until
oral rehydration therapy ORT was introduced
Diarrhoea is now the second leading cause
of mortality for children under 5, accounting
for 17% of all deaths, second only to
pneumonia, at 19%.
Rehydration
Mild: oral rehydration therapy ORT
Severe cases may need initial iv rehydration
Based on linked reabsorption of glucose &
sodium which continues to function nearly
normally when other mechanisms do not
Antibiotics rarely needed

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 Mechanism of Na+ Absorption
A. Diffusion through water-filled
Oral Rehydration Therapy
channels
Standard WHO rehydration fluid
Driven by electrochemical
gradient; Na 90, K 20, Cl 80, citrate 10, and glucose 111 (in mmol/L)
Osmolarity: 311 mmol/L
B. Co-transport with organic
solutes e.g. glucose, amino
acids In 2003, WHO/UNICEF changed the ORS formula to a
reduced osmolarity version. WHO/UNICEF reduced
osmolarity oral rehydration solution (ORS)
C. Cl- co-transport
Na 75, K 20, Cl 65, citrate 10, and glucose 75 (in mmol/L)
D. Na+-H+ counter-transport Osmolarity: 245 mmol/L

Reduced osmolarity rehydration solution is associated with reduced need

Na+ extruded by Na+-K+ pump for unscheduled intravenous infusions, lower stool volume, and less
at basolateral membrane vomiting compared with standard WHO rehydration solution.
Na+ absorption in small Disadvantage: risk of hyponatremia
intestine: B,C,D
Na+ absorption in large
intestine: A

Gastroesophageal Reflux Disease Gastroesophageal Reflux

GERD GERD

Expected to learn:
Definition of GERD Definition:
Causes and contributing factors Reflux of gastric content into
esophagus
Complications
Clinical presentation and diagnosis Normal Physiology
Lower esophageal sphincter
Treatment and physiological basis serves a barrier preventing reflux
of gastric contents into the
esophagus.

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 Gastroesophageal Reflux GERD
Causes:
Mutilfactorial
Depedent on:
Integrity of the esophageal mucosal barrier
Irritants in the food e.g. acid;
Other worsening factors: alcohol, smoking
Contributing factors:
motor abnormalities of esophagus
incompetence of the lower esophageal sphincter
increased intra-abdominal pressure e.g. after large meal,
heavy lifting, pregnancy; hiatus hernia
Gastroesophageal Reflux GERD
Treatment:
Dietary: small volume meals, avoid night snacks
Postural: sleep with head of bed elevated, avoid stooping or
bending
Stop smoking, avoid alcohol, weight reduction
Drugs to treat ulceration: Antacids, H2 blockers, PPI therapy
Drugs to strengthen lower esophageal sphincter
Gastroesophageal Reflux
GERD
Complications
From mild to severe
Inflammation and ulceration of esophagus
Scarring, narrowing & obstruction of esophagus
increase incidence of esophageal cancer
Symptoms and signs:
Dry cough, hoarseness of voice, soar throat
Heartburn
Regurgitation of gastric content into the mouth
Due to complications: dysphagia, Chronic bleeding and
anemia
Peptic Ulcer Disease
Expected to learn:
Definition of peptic ulcers
Causes of peptic ulcers: aggressive and
protective factors
Review on gastric mucosal defense and
regulation of gastric acid production
Complications of peptic ulceration
Clinical presentation and diagnosis
Treatment and its physiological basis
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Peptic Ulcers Peptic Ulcers
Peptic ulcer disease PUD
Definition
Ulcer = A break in the mucosal lining
Peptic ulcer = A break in the mucosal lining caused
by the digestive action of gastric juice
Causes of Peptic Ulcer
Stomach acid & pepsin
Bacterial infection: Helicobacter pylori
excess
Acid-pepsin production > Gastric mucosal protection
Location
Lower oesophagus (esophageal ulcer )
Stomach (gastric ulcer )
Duodenum (duodenal ulcer )
Aggressive Factors
HCl secreted by parietal cells
Stimulants for gastric acid secretion
Mechanism for gastric HCl secretion
Pepsin secreted as pepsinogen by chief cells
Pepsin is for the digestion of protein
Pepsin most active at pH<3
Increase secretion of gastric acid e.g. gastrinoma
can contribute to ulcer formation and multiple ulcer
formation in unusual sites
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 Aggressive Factors

Helicobacter pylori
75% PU have helicobacter pylori infection
H. pylori can liquefy & burrow through the
mucosal barrier
Cause chronic inflammation (gastritis)

Vander Human Physiology Ch 15

Gastric Mucosal Barrier

Protective Factors (Mucosal Defense)
Gastric mucosal barrier
Neutralization of gastric acid in duodenum by duodenal
juices (containing bicarbonate from Brunners gland,
pancreatic & biliary secretion)
Tight junctions between stomach epithelial cells restricting
diffusion of H+ into the underlying tissues
Rapid epithelial cell turnover to replace damaged cells
Secretion of mucus by mucous neck cells of gastric
glands & surface epithelial cells of stomach
Secretion of bicarbonate by surface epithelial cells
pH almost neutral at stomach surface while acidic
within stomach lumen
Layer of physical & alkaline barrier on stomach surface,
protecting against acidic, proteolytic gastric juice

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 Other Contributing Factors Complications of Peptic Ulcers

Relation to stress GI bleeding

Stress may increase acid secretion Vomiting of coffee ground material (hematemesis)
Role of alcohol, smoking Passage of tarry stool (melena)
Alcohol tends to break down mucosal barrier Perforation (perforated peptic ulcer PPU, causing
Smoking increases nervous stimulation of stomach secretion peritonitis )
Drugs Scarring and obstruction
NSAID (non-steroidal anti-inflammatory drugs) that block the
function of cyclooxygenase (Cox1 inhibitors), because
prostaglandin is essential for the secretion of mucus.
Drug induced gastritis

Clinical Features Diagnosis

Based on clinical features
Upper endoscopy
Abdominal pain most common
Allows biopsy for suspicious cases of cancer
Epigastric pain
Pain relieved by food or antacids
Contrast x-ray (Barium meal)
Pain related to food (hunger pain or pain after Diagnosis for the presence of H. pylori
eating)
Episodic (disappear then return for a few days or
weeks)
Nausea and vomiting
Present with complications
Upper GI bleeding: vomiting of coffee ground
material or passage of tarry stool
Rarely peritonitis caused by perforation
(perforated peptic ulcer PPU)
Vander Human Physiology Ch 15

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 Treatment Physiological Basis of Treatment
Neutralizing acid
Aim: Antacids HCL
Decrease acid production
Relief pain
H2 blockers
Reduce acid proton pump inhibitors PPI
Allow ulcer healing Eradication of Helicobacter pylori
Antibiotics + PPI +/- cytoprotective agent Antibiotics
Improving defense Vander Human Physiology Ch 15
Complications like PPU or uncontrollable Cytoprotective agents
bleeding may require surgical treatment Careful with use of aspirin & anti-rheumatic drugs
Life style modifications
Avoid alcohol & smoking,
Reduce stress
Surgical (when medical treatment fails or complications)
Vagotomy, gastrectomy

Malabsorption Malabsorption

Expected to learn: Definition

Definition of malabsorption
Pathophysiological mechanisms
Consequences of malabsorption
E.g. Lactose interance, pernicious
anemia, stearrhoea
A state arising from abnormality in the absorption of
food nutrients across the gastrointestinal tract
Malabsorption can be of ONE or MORE essential
nutrients, electrolytes, minerals or vitamins;

steatorrhoea: the excretion of abnormal quantities of fat with the

faeces owing to reduced absorption of fat by the intestine.

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 Malabsorption
Malabsorption
Causes:
1. Disorder of intraluminal digestion
Causes: Disorders in digestive enzymes or detergent within
1. Disorder of digestion the gut
2. Disorder of transport in mucosal cells Post-gastrectomy
Pancreatic insufficiency
3. Disorder of transport from mucosal cells
Deficiency of bile salt or impaired enterohepatic
circulation
Main feature: steatorrhea causing deficiency of fat
soluble vitamins

Malabsorption
Causes:
2. Disorder of transport in mucosal cells
Generalized mucosal damage
e.g. coeliac disease or extensive Crohns disease
results in generalized malabsorption
Absence of a specific enzyme
Lactose intolerance: deficiency in lactase
Pernicious anaemia: deficiency in Vit B12
Malabsorption
Causes:
3. Disorder of transport from mucosal cells
Rare
E.g. Blockage of lymphatic system responsible for
absorption of chylomicrons
e.g. abdominal lymphoma, TB

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 Malabsorption
Malabsorption of one or more essential nutrients, electrolytes,
minerals or vitamins;
Clinical features:
General malnutrition
Loss of weight & energy
Slow deterioration in health
Failure to grow and thrive in a child
Diarrhea (steatorrhoea with deficiency of fat soluble vitamins e.g.
osteomalacia from Vit D deficiency, delay in blood clotting due to Vit K
deficiency)
Abdominal pain & distension
Anaemia e.g. megaloblastic anaemia from Vit B12 deficiency
Evidence of specific deficiency
Edema from protein deficiency

Normal Lactose Metabolism

Lactose is the major carbohydrate in milk
In the small intestine, lactose is digested by lactase into
glucose and galactose
Glucose and galactose then absorbed by active transport in
small intestine
Lactase Deficiency Normally lactase is present at birth and allows nursing
Lactose Interolerance infants to digest lactose in breast milk
Some individuals have a decline in lactase since the age of 2,
leading to lactose intolerance in adulthood
The frequency of decreased lactase activity range from 5%
in northern Europe, 71% in Sicily to more than 90% in some
African & Asian countries

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 What Happens with Lactase Deficiency
Lactose containing fluid past into large intestine, get
digested by bacteria in large intestine, producing
gas (which distends the colon, producing pain) &
short-chain fatty acids (which cause fluid movement
into the lumen of the large intestine, producing
diarrhoea)
Osmotic diarrhoea
Vitamin B12 and Anaemia
Vitamin B12 metabolism
We obtain vitamin B12 from the diet
Absorption of Vitamin B12 at the ileum
depends on intrinsic factor
Intrinsic factor is secreted by parietal cells of
the stomach
Vitamin B12 is required for proper development
of RBC and normal function of the nervous
system
Lactose Intolerance
Clinical features of lactose intolerance:
abdominal discomfort, pain, bloating, flatulence and
diarrhea after ingestion of milk and milk products
symptoms vary in severity according to the volume
of milk or milk product intake and the amount of
lactase present in the intestine
Treatment:
Avoid milk & milk products
take pills containing lactase along with milk
Pernicious Anemia
Definition:
Anemia is a decrease in the
number of red blood cells
Vitamin B12 deficiency leads to anemia
Pernicious anemia is a
decrease in red blood cells that occurs
when the body cannot properly absorb
vitamin B12 from the gastrointestinal
tract.
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 Pernicious Anaemia
Pernicious Anaemia Consequences:
Causes: Vitamin B12 deficiency
Megaloblastic anaemia
Weakened stomach lining (Atrophic gastritis)
Bodys immune system acting against parietal cells Features of anaemia: Pale skin, fatigue,
shortness of breath, dizziness, weight loss
(Autoimmunity against parietal cells)
RBC bigger than normal (megaloblastic)
Autoantibodies against intrinsic factor
Neurological complications

Treatment:
Vit B12 replacement by injection or nasal spray
(not oral)

References
1. Vander, Sherman, Luciano, Human Physiology:
The mechanisms of Body Function Ch 15
2. Guyton & Hall, Textbook of Physiology Ch 66.
3. Ivan Dajanvoc, Pathophysiology Ch 7.

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