BHS 116.2 – Physiology
Notetaker: Vivien Yip
Date: 1/30/2013, 1st hour
Page1
****Note: Since Mediasite is down the the MP3 lecture is not uploaded, these are the notes I got only in class, so
please let me know if you spot any mistakes thanks!*****
Clicker Q
Which of the following is not a function of the liver?
- Metabolism of carbohydrate
- Detoxification
- Storage of bile
Question on final regarding reading assignment: Sherwood 8th Ed, Ch. 16, p. 629; 7th Ed, Ch. 16, p. 634
Lecture 17 GI Pathology: Esophagitis, Gastritis and Ulcers, enteritis and colitis
Describe the pathophysiology and symptoms of esophagitis
Esophagitis
- Injury and subsequent inflammation of the esophagus is a common disorder worldwide
- Incidence in the US is about 5%
- Primarily limited to adults over 40, but infants and children can also be affected
- While many factors can contribute to developing esophagitis, reflux of gastric contents in the lower
esophagus is the most important (reflux esophagitis or GastroEsophageal Reflux Disease/GERD)
o The damage caused by the gastric juices leads directly to mucosal injury and inflammation
 Esophageal tissue is not meant to resist high acidic environment, a lot of HCl is pumped
in the stomach to help with digestive process
 Squamous cells of esophagus does not have protection against the acid
 Pepsin is digestive enzyme present in the stomach
 Cells of esophagus will not be resistant to:
 Combination of HCl and pepsincauses damage and injury  inflammation
- Other origins of inflammation include:
o Prolonged gastric intubation (during surgery)
o Uremia (high concentration of urea in the blood)
o Ingestion of corrosive or irritant substances
o Radiation (Cancer treatment)
o Chemotherapy (Very toxic to normal cells of the body)
- Histology
o Increased # of eosinophils and neutrophils
o Immature squamous epithelium
o In lower part of esophagus
- Symptoms
o Dysphagia (difficulty swallowing) – inflamed esophagus
o Heart burn
o Hematemesis (vomiting blood)
 On rare occasion, chronic symptoms are punctuated by severe chest pain – mimicking a
heart attack
 Persistent esophagitis could lead to Barrett esophagus (metaplasia from stratified
squamous cells to columnar)
 Columnar cells are more protective in this type of environment
 Cells can now resort to more cancerous type cells  can lead to esophageal
cancer
 Also see more goblet cells to secrete more mucous
 Smooth epithelium in normal esophagus  broken and destroyed esophageal
tissue in esophagitis
Describe the causes of esophageal varices
Esophageal Varices
- Dilated esophageal blood vessels
- Increased portal blood pressure forces blood into collaterals (drain esophagus)
BHS 116.2 – Physiology
Notetaker: Vivien Yip
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-
Date: 1/30/2013, 1st hour
Page2
o When these include the esophageal mucosal plexus, dilated tortuous vessels develop called varices
Caused by any factor that creates portal hypertension
o Most often cirrhosis of the liver
 65% of cirrhotic patients develop varices
o Portal hypertension backs up the collaterals and cause dilations of blood vessels in the lumen of
the esophagus
These varices are symptomless until they rupture and cause massive hematemesis
o Then you get coughing/vomiting large amounts of blood
Death results in about 20-30% of those patients who rupture due to fatal loss of blood
Describe the differences between the types of hiatal hernias
Hiatal Hernia
- Another esophageal issue
- Gastroesophageal junction is where the esophagus links up with the stomach
- Stomach should be BELOW the diaphragm (normal)
- Hiatal hernia is a dilated segment of the stomach that protrudes above the diaphragm
o Incidences increase with age (seen much more with older adults)
- 2 types:
- 1. Sliding hernia
o 95% of cases
o Bell shaped dilation
- 2. Paraesophageal hernia
o Portion of the greater curvature of the stomach enters the thorax
o Much more dangerous type*
o Potential strangulation of blood vessels that run along the greater curvature of the stomach
o If that part of the stomach bulges up above the diaphragm, the diaphragm can block those blood
vessels
o Potential for ischemia and death of stomach cells
- Symptoms
o Both types have mucosal ulceration, bleeding and perforation on occasion
o Heartburn and regurgitation (reflux) are not symptoms caused by the hernia
 Only 9-10% of patients have this
o Paraesophageal hernias can become strangulated and if undetected, ischemic
 Can be detected with barium
Describe the pathophysiology of chronic and acute gastritis and their differences
Gastritis
- Defined as inflammation of the gastric mucosa
- Most cases are chronic, but some are acute
Acute gastritis
o
o
-
-
Transient (can be cured and gone- non persistent)
may be accompanied by hemorrhage into the mucosa and if severe, sloughing of superficial
mucosa (erosion)
o can lead to acute GI bleeding
Symptoms
o Asymptomatic OR:
o Epigastric pain (upper region of abdominal area)
o Nausea
o Vomiting
o Hemorrhage (occasional)
o Hematemesis (vomiting large amounts of blood) and potentially fatal blood loss
Approximately 25% of patients who take daily aspirin for rheumatoid arthritis (or any other inflammatory
disease) develop acute gastritis at some time in their life
Often associated with
o Drugs:
BHS 116.2 – Physiology
Notetaker: Vivien Yip
-
-
Date: 1/30/2013, 1st hour
Page3
 NSAIDS
 Chemotherapy drugs (can cause esophagitis and acute gastritis)
o Alcohol
o Smoking
o Stress (trauma, burns, surgery)
 High amounts of cortisol can lead to stomach secretions
 Knocks down immune system making the stomach more susceptible to damage
o Infections (systemic: salmonellosis)
o Ischemia
Often results in:
o Increased acid secretion
o Concomitant decrease in bicarbonate secretion
 pH will decrease, stomach cannot protect itself from the acidic environment
o Decreased blood flow (resulting in ischemia)
 As tissues die, the mucus producing cells die along with them
o Disruption of the protective mucus layer
o Direct damage to the epithelium
 Since protective layers are absent
All of these can act synergistically to worsen the injury to the gastric mucosa
Can see large areas of gastric hemorrhage also known as erosions (superficial mucosa is eroded away)
Chronic gastritis
- More common form of gastritis
- Chronic mucosal inflammatory changes, leading to mucosal atrophy and epithelial metaplasia
o Defenses will be down
o Cell will change type to make a more protective cell type to withstand the damage
o Metaplasia causes change in cell type
- Chronic changes in the epithelium, becoming dysplastic, may constitute a background for the development
of gastric carcinoma
- In Western cultures, histopathologic changes indicative of chronic gastritis are found in 50% of the
population in later life (autopsy)
o Undiagnosed until death
- Frequent causes
o Chronic helicobacter pylori infection
o Autoimmune destruction of parietal cells in association with pernicious anemia
o Toxicity
 Alcohol and smoking
o Mechanical trauma
o Radiation treatment (cancer treatment)
o Post-surgical
 Surgery in abdominal region can disrupt stomach function and can lead to chronic
gastritis
Helicobacter Pylori
- The most important of these associations is the chronic infection with Helicobacter pylori
- This bacteria is present in 90% of patients with chronic gastritis affecting the antrum
- Colonization increases with age reaching about 50% in US adults over 50yo
- Most infected persons are asymptomatic
o Drugs to eradicate H. pylori are critical in effective treatment of chronic gastritis and peptic ulcer
o Easily treated with antibiotics
Chronic gastritis
- Continued inflammation of mucosa leads gradually to gastric atrophy
- Leads to loss of stomach secretions
- Achlorhydria (autoimmune)/Hypochlorhydria
o Direct attack on parietal cells
BHS 116.2 – Physiology
Notetaker: Vivien Yip
Date: 1/30/2013, 1st hour
Page4
When stomach pH can’t get below 6.5 after maximal gastric stimulation due to lack of HCl
secretion by parietal cells
o Produce very little if any HCl
o Not conversion of pepsinogen to pepsin
o No protein digestion (pepsin activates other enzymes)
o More susceptible to other bacterial infections (usually died off in acidic environment)
 Reduced HCl is hypochlorhydria
o Leads to some digestive issues
Pernicious anemia
o Related to Vit B12 absorption due to decreased intrinsic factor production by parietal cells
(usually only caused by autoimmune form)
o
-
- Normal mucosa, always is going
to be in contact with damaging factors:
HCl, pepsin, physical movement, drugs,
are damaging to the mucosal layer of the
stomach
- Typically have protection in
place
- When damaging factors are
present With Chronic Gastritis, start to
get changes in mucosal layer
- Atrophy: don’t see much
involution in the chronic gastritis
- Mucosal layer do not have
neutrophils in the normal gastric mucosa
- Metaplasia into more protective
cell type
- Can easily seen with biopsy of
stomach lining
Describe the pathophysiology of peptic ulcers
Peptic Ulcer
- Remitting, relapsing lesions
o Develop, heal, later months/years, back again
- An excoriated (raw irritated worn off area) area of the mucosa caused by the digestive action of the gastric
juices
- Erosion of epithelium, submucosa and mucosal layers
- Location:
o Any GI tract portion
o Most frequent in 1st portion of duodenum (80%)
 Chyme coming out of the stomach is most acidic and hits this part of the intestines first
 If we don’t get enough bicarb from the pancreas secreted early enough, will get break
down
o Antral portion of stomach
 Region before the small intestine
o Gastroesophageal junction
 Where esophagitis also occurs
- In Western nations, peptic ulcers develop in up to 10% of the population at some point during life
- In the US ~4million people have peptic ulcers
- 3000 people die each year due to complications
o Sepsis and massive bleeding
BHS 116.2 – Physiology
Notetaker: Vivien Yip
-
-
Date: 1/30/2013, 1st hour
Page5
Likelihood of developing an ulcer is ~10% for US males and 4% for US females
Appear to be produced by an imbalance between the GI defense mechanisms and the damaging forces
Gastric acid and pepsin are requisite for all peptic ulceration
o Physically break down and destroy the mucosa
o Damage is due to the gastrin and HCl on the mucosa
H. pylori is found in virtually all duodenal ulcers and in 70% of gastric ulcers
o All duodenal peptic ulcers will have H. pylori
o H. pylori can break down protective mechanisms of stomach
o Recent work has focused on how the bacteria breaks down the mucosal defenses
 Induces inflammatory and immune responses
 Secretes toxins
- Normal balance
between aggressive and
defensive forces
- Peptic ulcers are
created due to an impaired
defensive force
o Even normal
aggressive force is strong
enough to deterioriate
epithelium of the stomach
- Adding of aggravating
causes will contribute to the
formation of peptic ulcers
- Result in degeneration
of epithelium and mucosa
-
-
-
Chronic gastritis: alteration in
mucosal layer, metaplasia, all
restricted to the mucosal layer*
Peptic ulceration: goes completely
through mucosal layer, eats through
muscularis mucosa, starts to
damage to submucosa to the point
where there is an inflammation
causing fibrosis in the submucosal
layer of the stomach
Digestive juices will continue to eat
their way through all the layers,
nothing to stop the gastrin and
pepsin action of mechanism
Treatment of Peptic Ulcer
- Many drugs are useful to allow healing of the mucosal damage
o Antibiotics: eliminate H. pylori
o Acid suppressant drugs: omeprazole
o Histamine 2 blockers: cimetidine
 Triggers HCl release, therefore blocking histamine blocks HCl release
o Acid neutralizers: antacids
o Drugs to increase the barrier: sucralfate
- Avoidance of secretogogues
BHS 116.2 – Physiology
Notetaker: Vivien Yip
Date: 1/30/2013, 1st hour
Page6
Describe the pathophysiology of infectious enterocolitis and ulcerative colitis
Infectious enterocolitis
- Intestinal disease
o Consisting of diarrhea and sometimes uclers or inflammation of the small or large intestine
 Viral gastroenteritis
 Typically destroy epithelium and prevent absorption of fluid and nutrients
 Small and large intestines
 Bacterial enterocolitis
 Can proliferate in lumen and release an enterotoxin (toxigenic) or can directly
destroy epithelium (enteroinvasive)
 Alternatively one can ingest a preformed toxin
 Don’t invade the cell, but releases toxic agents
 Enterotoxin acts on epithelium of small intestines
 Enteroinvasive bacteria gets inside the cells and destroy them
- Many infectious organisms can lead to diarrhea
o Most frequent
 Viral
 rotavirus (infants and toddlers)
 Norwalk virus (older children and adults)
 Bacterial
 enterotoxigenic e. coli (produces toxic protein)
 enteroinvasive salmonella (directly invades and destroys the cell- much more
serious)
o Worldwide – 12, 000 deaths per day (dehydration from severe diarrhea and unable to retain the
fluids) among children in developing countries. 50% of all deaths worldwide in children under age
5
o In developed nations – still see average of 2 cases per person per year, second only to the common
cold in frequency
- In 40-50% of cases no specific infectious agent can be identified
o Pathologic manifestations are as variable as the infectious sources
o Can be viral or parasitic or bacterial
- Clinical features of bacterial enterocolitis (most common type)
o Ingestion of pre-formed bacterial toxins (food poisoning)
o Symptoms develop in a matter of hours, with explosive diarrhea and acute abdominal distress
o Some bacterial neurotoxins can lead to rapid death (botulinum toxin)
o Most affects the GI epithelium
- End result is loss of fluid (dehydration)
o Sometimes so severe that death ensues
o Short term complication
- Cell damage or destruction of the intestinal mucosa which could lead to sepsis and perforation
- Additionally, malabsorption of nutrients can occur due to shortened transit times and tissue damage and
inflammation
o Long term complication
 Malnutrition
 Damage to epithelium: sepsis
 Broken wall through intestine
 Intestinal content and bacterial leak out to abdominal cavity
- Parasitic disease and protozoal infections affect more than half the world population on a chronic or
recurrent basis
o Nematodes (roundworms)
o Flatworms (tapeworms and flukes)
o Protozoa (crytosporidia)
o Amebic dysentery (Entamoeba)
o Giardia (fairly prevalent in the outdoors)
BHS 116.2 – Physiology
Notetaker: Vivien Yip
Date: 1/30/2013, 1st hour
Page7
Describe the 2 inflammatory bowel diseases- Crohn’s disease and Ulcerative colitis
Crohn’s Disease
- Idiopathic inflammatory bowel disease
o Unknown cause, abnormal local immune response, CD4+ T-cell mediated
o Genetic predisposition
o Chronic and relapsing disorder, lasts for long period of time but will have bouts of symptoms, no
symptoms, keeps coming back
o Granulomatous: involves entire GI tract, but most often the intestines (sm & lg)
 Ileum is most common site
o Ocular involvement (iritis and uveitis)
- Inflammation and ulceration of the GI tract
- Symptoms:
o Diarrhea, fever lasting days to weeks, and abdominal pain
- Mucosal surface demonstrates an irregular nodular appearance (granulomas) with hyperemia (blood) and
focal superficial ulceration
Ulcerative Colitis
- Idiopathic inflammatory bowel disease
- Colitis: restricted to large intestine and colon
- Unknown cause, strong hereditary component, abnormal local immune response CD4+ Tcell mediated
- Extensive areas of the colon become inflamed and ulcerated
- Leads to excessive motility and enhanced secretions: diarrhea
- Non-granulomatous
- Ocular symptoms may include uveitis
- Mucosa becomes eroded, remaining islands of mucosa are called pseudopolyps (little islands of normal
mucosa)
Crohn’s Disease vs Ulcerative Colitis
Crohn’s disease
Ulcerative colitis
- Transmural and involve all 3 linings of the
- Primarily affect the mucosa and submucosa
wall
- Does not affect muscularis mucosa
- Inflammation affects all 3 layers
- Erosion of the layers
- Skip lesions: regions of diseased tissues
- Get pseudopolyps
followed by regions of normal tissue
- Only in colon (large intestine)
- Continuous legions of affected tissue
- Not continuous
- Large and Small intestine
- Primarily in ileum
Clicker Q
- H. Pylori could cause all of the following except
o Ulcerative Colitis