GI

Pathophysiology

Dr. Jennifer Rogers

April 14, 2009
 Upper GI Tract
 Upper tract- the mouth, esophagus, and stomach.
 Acts as an intake source and receptacle through which
food passes and initial digestion takes place
 Middle GI Tract
 Middle tract- duodenum, jejunum,
and ileum
 Most digestive and absorptive
processes
 Lower GI Tract
 Lower tract-
cecum, colon,
and rectum
 Serves as a
storage
channel
 Accessory organs
 Accessory organs- the
salivary glands, liver, and
pancreas, gall bladder
 Produce digestive
secretions that help
dismantle foods and
regulate use and storage.
 Clinical Manifestations
 Anorexia

 Nausea

 Vomiting (emesis)

 Hematemesis

 Melena
 Tarry-dark stool;
 source above ileocecal valve
 Occult- microscopic
 Diarrhea
 Passage of more than 200g per day of feces

 Depends on origin

 Osmotic vs. secretory

 Osmotic caused by fiber
 Secretory caused by a pathogen (cholera)

 Inflammatory-inflammatory cells in the diarrhea vs.

noninflammatory
 Constipation
 Infrequent passage of stool

 Could be a primary problem or as a problem association with

another disease condition

 Causes
 Failure to respond to the urge to defecate- the longer it sits, the
harder it gets.
 Inadequate dietary fiber
 Inadequate fluid intake
 Weakness of the abdominal muscles
 Inactivity
Esophagus
 Conduit

 Pass through the

mediastinum

 Two sphincters
 Helps to prevent
reflux
Esophageal Sphincter
Prominent Cricopharyngeus
 Lower Esophageal Sphincter
 Regulates the flow of food from the esophagus into the
stomach

 Internal-Circular muscles of the distal esophagus

 External- portion of the diaphragm

 Oblique muscles of the stomach also help to maintain the

tone

 Gastric distension and high fat meals increase relaxation

Swallowing

Dysphagia
 Oropharyngeal
dysphagia
 Esophageal dysphagia

 Odynophagia

 Pyrosis

 Achalasia
 Three causes
LES Innervation
Gastroesophageal Reflux
Disease (GERD)
 Incompetent LES
 Open too often

 Acid hypersecretion

 Delayed gastric
emptying

 Decreased salivation
 LES and GERD
 Weak Basal LES Pressure

 Inadequate LES Response to Increased Abdominal

Pressure

 Inadequate LES Response to Gastric Contractions

 Transient Relaxation of the LES

 Dysfunctional anti-
reflux barrier

Anatomic abnormality Physiologic abnormality

LES LES
Hiatal hernia Hypotension relaxation

Decrease the length of Strain Free

the high pressure zone induced reflux

Acid refluxes into

distal esophagus

Disruption of Acid reaches

Cell edema Mucosal
tight intrercellular
and death inflammation
junctions space
 GERD- symptoms
 Reflux involves mucosal injury to the esophagus,
hyperemia, and inflammation

 Heartburn (pyrosis)
 30-60 min after eating
 Made worse by bending at the waist
 Most often occurs at night

 Belching and chest pain

 Respiratory symptoms- wheezing, chronic cough, and

hoarseness
Chronic GERD
 Persistent reflux- cycle of mucosal
damage that causes hyperemia,
edema, and erosion of the luminal
surface

 Strictures
 Fibrosis that leads to narrowing of
esophagus

 Barrett’s esophagus
 Normal squamous
mucosaabnormal columnar mucosa

 Increased risk for cancer

 Treatment of GERD
 Conservative measures first-

 Avoidance of positions and conditions that increase GERD

 Avoid large meals and foods that reduce LES tone
 Caffeine, fats, chocolate

 Smoking and alcohol

 Meals eaten sitting up
 Avoid bending for long periods of time
 Weight loss (GERD is typically seen in obese patients)

 Aggressive treatment
 Block gastric acid secretion
 Drugs that increase motility
 Stomach
 Reservoir for contents entering the digestive tract

 Food is churned, mixed with HCl and pepsin (activated by HCl)

 Gastric Mucosal Barrier
 Acids are important for the indiscriminate digestion of
food

 Mucosa- water-repellent hydrophobic layer

 Bicarb- trapped in the mucus gel

 Restitution- the ability to “send rescue” to an area of

damaged mucosa

 High gastric blood flow

 Gastritis
 Damage to the gastric mucosa with acute inflammation,
necrosis, and hemorrhage

 Acute gastritis

 Chronic gastritis
 Autoimmune gastritis
 Multifocal atrophic gastritis
 Chemical gastropathy
 Helicobacter pylori gastritis
 Helicobacter Pylori gastritis
 H pylori was cultured and characterized in 1983

 Common in the general population and usually harmless

until for some reason they start to proliferate a lot more
and start to cause people to experience symptoms

 Produces urease and mucinase. The urease is used to

convert water and urea to ammonia which neutralizes the
acid surrounding the bacteria and the mucinase breaks
down the mucus layer. The breaking down of the mucus
layer leaves that are vulnerable to damage by acid which
leads to inflammation and formation of an ulcer.
 Peptic Ulcer Disease
 Group of ulcerative disorders that occur in the upper
gastrointestinal tract.

 Exposes submucosal layer to gastric contents

 autodigestion
 H. pylori NSAID

Damaged mucosal barrier

Decreased function of mucosal cell

and decreased quality of mucus

Back diffusion of acid into

gastric mucosa
Formation of
Conversion of
Histamine
Pepsinogen

Further erosion of
Increased acid secretion
mucosa/ bleeding

Ulceration
 Duodenal
 Seen in a wide variety of patients, pain between
meals and in the early morning

 Most often occurs in the bulb close to the stomach

H. pylori infection

 toxins and enzymes that promote inflammation and

ulceration

 hypersecretion of stomach acid and pepsin

 use of NSAIDs
 PGs: mucosal blood flow / secretion of HCO3-

 high gastrin levels

 acid production by cigarette smoking

 Gastric Ulcer
 tend to develop in the antral region, adjacent to the acid-secreting mucosa
of the body

 Seen most in the elderly, pain not associated with eating; can be felt
anytime

 Pathophysiology
 primary defect is an increased mucosal permeability to H +
 gastric secretion tends to be normal or less than normal

Clinical Manifestations

 ~duodenal
 except pain can be immediately after eating
 tend to be chronic
 ↑ anorexia, vomiting, and weight loss
 Stress Ulcers
 an acute peptic ulcer related to severe illness, neural injury, or
systemic trauma

 Tend to get more than one at multiple sites

 Ischemic ulcers
 within hours of event (hemmorhage, heart failure, severe burns-
Curling ulcer)

 Cushing ulcers
 develop as a result of a head trauma / brain surgery

 decreased mucosal blood flow

 overstimulation of vagal nuclei… (hypersecretion of acid)

 Cancer of the Stomach
 Relatively uncommon tumor, accounts for 3% of malignancies

 Most common fatal cancer in the US

 Genetic predisposition

 More common in men and Type A blood (as is H. pylori)

 Carcinogenic factors (N-nitroso compounds and benzopyrene)

 Infection with H. pylori appears to serve as a co-factor

 Usually asymptomatic until late in their course

 Symptoms are vague- indigestion, anorexia, weight loss, vague pain,

and vomiting
 Small Intestine
 Enormous surface area which assist in efficient absorption.

 Carbohydrates

 Proteins

 Lipids

 Water

 Electrolytes

 Iron
Stomach

Duodenum Iron, calcium, folic acid

Carbohydrates, proteins, fats

Jejunum

Bile salts, B12

Ileum

Cecum
 Irritable Bowel Syndrome
 Functional gastrointestinal disorder characterized by
abdominal pain and constipation with or without mucous
discharge and episodic diarrhea

 Believed to be by result from dysregulation of intestinal

motor and sensory function modulated by CNS

 Increased motility and abnormal intestinal contraction in

response to psychological and physiologic stress
 Clinical Features
 Abdominal pain relieved by defecation

 Altered frequency of bowel movement

 Definition of constipation

 Sensation of incomplete evacuation

 Passage of mucus upon defection

 Abnormal myoelectric and motor activities in the GI tract.

 Inflammatory Bowel Disease
 Crohn’s disease and ulcerative colitis

 Commonalities
 Inflammation of the bowel
 Lack confirming evidence of a proven causative agent
 Pattern of familial occurrence
 Accompanied by systemic manifestation
 Causes

 Hereditary predisposition

 Autoimmune reaction, possibly triggered by some

relatively innocuous environmental agent

 Infectious in origin
 Systemic Manifestations
 Arthritis (spine, sacroiliac joint, and large joints of the arms and leg)

 Inflammatory conditions of the eye

 Skin lesions- erythema nodosum

 Hypercoagulability of the blood

 Stomatitis
 is an inflammation of the

mucous lining of any of the

structures in the mouth

 Autoimmune anemia
 Lumen

Bowel Walls
 Crohn’s Disease
 Can affect any area from the mouth to the
anus

 Recurrent granulomatous type of

inflammatory response

 Progressive, relentless, and disabling

 Hallmark-sharply demarcated
granulomatous lesions that are surrounded
by normal appearing mucosal tissue

 Skip lesions- the inflammation occurs

sporatically in bands, it’s not continuous

 All layer of bowel could be involved but

the submucosal mostly involved

 Ulcerations can produce longitudinal and

transverse inflammatory fissures that
extend into the lymphatics
 Clinical Course
 Often variable: periods of exacerbation and remission

 Symptoms are often related to the location of the lesions (nutritional

deficiencies specifically absorption issues are possible)

 Diarrhea (small amounts of blood)

 Remember depending on where it occurs diarrhea can be highly voluminous and
cause malabsorption. This disease would likely lead to inflammatory diarrhea

 Colicky pain- severe abdominal pain caused by spasm

 Weight loss

 Fluid and electrolyte disorders

 Malaise
 Dysfunctional intestinal
epithelium- impairs innate
immune system

Allows for frequent

exposure to unknown
Activates antigen/Results in overly
macrophages aggressive TH1 response

Secrete more Cytokines recruit

cytokines inflammatory cells to
intestinal mucosa
Further
stimulates Amplified and sustained
TH1 response inflammatory response

Transmural inflammation

Loss of Extraintestinal
Diarrhea Abdominal pain
absorptive manifestations
surface
 Ulcerative Colitis
 Nonspecific inflammatory condition

 **confined to the rectum and colon**

 **Affects primarily the mucosal layer**

 **Affected site tends to be continuous**

 Leads to the formation of pinpoint mucosal hemorrhages,

which can become necrotic and ulcerate.

 As a result of the inflammatory process, the mucosal layer

develops tongue-like projections that resemble polyps
 Symptoms
 Diarrhea
 Because the mucosal layer is involved, the stool typically
contain blood and mucus

 Mild abdominal cramping

 Anorexia

 Weakness
 Treatment
 broad-spectrum antibiotics

 immunosuppressive agents
 Like steroids

 Surgery
 Resection of the affected area
 Crohn’s Disease Ulcerative Colitis
Terminal ileum Commonly Seldom
Colon Usually Always
Rectum Seldom Usually
Bile duct Not associated Common sclerosis
Distribution Patch areas (skip lesions) Continuous
Depth Transmural Shallow, mucosal
Fistulae Commonly Seldom
Surgery Often returns Cure
Smoking Higher risk Lower risk
Cancer risk Lower risk Higher risk
Biopsy Non-peri-intestinal crypt Crypt abcesses and
granulomas cryptitis
 Appendicitis
 The appendix becomes
inflamed, swollen, and
gangrenous, and it eventually
perforates if not treated

 Thought to be caused by
intraluminal obstruction with a
fecalith (hard piece of stool) or
twisting
 Occlusion of the
lumen

Continued mucosal
secretions

Increase in
intraluminal pressure

Limit venous blood Gangrene and

flow perforation

Hypoxia
Arterial circulation
becomes thrombosed
Mucosa ulcerates

Further increase in
Bacteria invasion
intraluminal pressure
 Diverticular Disease
 Herniations/outpouchings of mucosa through the muscle
layers of the colon wall, especially the sigmoid colon
 Definitions
 Diverticulum

 Diverticulosis

 Diverticulitis

 Diverticular disease
 lumen
mucosa
circular muscle
blood vessel

diverticulosis
 Prevalence
 Common in Western society,

 Almost non-existent in many African nations and

underdeveloped countries

 Suggests dietary factors

 Decrease in physical activity

 Effects of aging
 Law of Laplace
 T=PxR

 T- tension in the wall of a cylinder

 P- pressure within

 R- radius

 If one assumes that the tension of the circular muscle of

the colon is constant, the intraluminal pressure will be
greatest where the lumen is narrowest
 Sigmoid Colon!
 Diverticulitis
 Complication of diverticulosis

 Inflammation and gross or microscopic perforation of the

diveritculum.
 Malabsorption Syndrome
 Constellation of symptoms
arising from multiple
causes

 Persons with conditions that

diffusely affect the small
intestine and reduce its
absorptive functions share
certain common features

 Celiac Sprue, Crohn’s, and

bowel resection are
common causes of
malabsorptive diseases
 Symptoms
 Diarrhea

 Steatorrhea

 Flatulence

 Bloating

 Abdominal pain, cramps, abdominal distention

 Weakness, muscle wasting, weight loss

 Easy bruising and bleeding

 Bone pain
 Celiac Sprue
 Rare chronic disease in which
there is a characteristic mucosal
lesion of the small intestine

 Impairs nutrient absorption

 Improves when gluten is removed

the diet

 Believed to be a immunologic
response to gluten which leads to
an immune attack of the intestinal
lining that causes loss of
absorptive villi
 Colorectal Cancer
 Second leading cause of cancer death in the US

 Most cases begin as polyps (elevation of the intestinal surface)

 Risk Factors
 Age (older than 50)

 Family history of cancer

 Inflammatory bowel disease

 Diet

 Asprin intake
 Chuck Bass
 24 year old white male presents to urgent care with
complaints of rectal bleeding and weakness. Five days
age he noticed bright red blood in his stools. Daily
bowel movements have increased to five or six with
significant diarrhea. He has been weak for
approximately 2 ½ days.

 Mother has SLE

 Maternal grandmother had Graves

 Aunt has Myasthenia Gravis

 Lab values
 Bp 120/75

 P 93

 RR 20/min

 T 99.4

 Wt 161

 Ht 5’10

 (+) pallor, (+) tender abd

Na (135-145) BUN (8-20) Plt (150-450) AST (0-35)
K (3.5-5.0) CR (.6-1.2) ESR (<10) ALT (7-56)
Cl (101-112) Hb (13.6-17.5) CRP (0-.5) T (.1-1.2)
HCO (22-32) Hct (39-49) Ca (8.5-10.5) PT (11-15 sec)
Glu (60-110) WBC (4.8-10.8) Po4 (2.5-4.5) Alb (3.4-4.7)
 Proctosigmoidoscopy
 Pseudopolyp formation

 Erosion of mucosa

 Ulcerations in submucosa

 No dysplasia

 Inflammation limited to rectum and sigmoid colon

 Marked hemorrhaging of capillaries in the mucosa

observed