KRISTIN FRIBERG (edited by VISHAL KUMAR) 2021/2022
PATHOPHYSIOLOGY FINAL EXAM
1. The pathophysiology of the gastrointestinal system - the diseases of the
stomach and the small intestine
The possible pathomechanism of peptic ulcer and duodenal ulcer; their symptoms and the
principles of treatment
Peptic ulcer disease:
- Peptic ulcers are defects in the GI mucosa extending through the muscular layer
- Can lead to small chronic bleeding which can lead to iron deficiency anemia
Etiology:
- H. pylori infection
- Non-steroidal anti-inflammatory drugs (NSAIDs) (e.g. even chronic low
dose/100mg/Aspirin)
- Viral infections
- Gastrinoma (Zollinger-Ellison syndrome)
- Idiopathic
H. pylori:
- H. pylori tests can be false negative in at least 10% of patients (use of antibiotics and
proton pump inhibitors)
In different locations, it is possible to buy proton pump inhibitors over the
counter patient can mask their symptoms without knowing it
- Ulcer incidence in H. pylori – infected individuals is 6-10x higher than in uninfected
subjects
- H. pylori colonizes the antrum – the lower part of the stomach:
H. pylori produces NH3 in response to the low pH (acidic) more
favorable environment for the bacteria NH3 irritates mucosal
layer to produce even more acid
An ongoing immune response further damages the mucosal layer
hyperacidic response
Diagnosis of H. pylori infection:
Urease activity of H. pylori can be used as diagnostic procedures:
1) Urease breath test
Give carbon-isotope labeled urea to the patient
bacteria cleaves the urea and isotope-labeled CO2 will
be produced measure it from the exhaled air
2) Direct urease test from biopsies or histological evaluation
of them
If we suspect H. pylori infection or the patient has reflux disease perform
esophagoscopy/gastroscopy
,KRISTIN FRIBERG (edited by VISHAL KUMAR) 2021/2022
Chronic NSAID use:
Chronic NSAID use is a common cause of refractory and complicated ulcers:
- Low-dose aspirin (for prevention of thrombotic events) increases risk of GI-bleeding
by 60%
- Proton pump inhibitor use reduces the risk of ulceration it reduces the rate of
ulcer disease in NSAID users at risk
- NSAID in peptic ulcer disease:
NSAIDs will inhibit all types of COX every type of prostaglandin
production will be reduced (PGl usually inhibit acid production) inhibition
of inhibition ↑ acid production
Symptoms and outcomes of peptic ulcer disease:
Symptoms:
- Dyspepsia epigastric pain or discomfort is the most prominent
- Approximately 70% of peptic ulcers are asymptomatic
Complications:
- In 40-50% gastroesophageal reflux disease (GERD)
- Bleeding into the GI-tract ( anemia), rarely hematemesis (vomiting fresh blood)
- In 2-10% perforation of the bowel wall: sudden severe, diffuse abdominal pain
In untreated patients, it usually leads to peritonitis shock death
- Gastric cancer (rare)
The pathophysiology of lactose intolerance and celiac disease; their symptoms,
complications and treatment options
DISEASES OF THE INTESTINES
Leading symptoms:
- Abdominal pain, malabsorption, diarrhea (with or without blood)
- Diarrhea is one of the leading symptoms, because there is a huge daily flow rate in
the intestines minor change in the mucosal layer (e.g. absorption problem) will
lead to several liters fluid loss (= diarrhea)
Lactose intolerance:
- Intolerance to lactose-containing foods
- Most common (>70%) intestinal disease worldwide
- Prevalence is low in children <6 years and increases with age
- Newborns and adults with low lactase activity can adapt to persistent lactose
ingestion through bacterial conversion of lactose to short-chain fatty acids that can
be absorbed in the colon as energy sources
,KRISTIN FRIBERG (edited by VISHAL KUMAR) 2021/2022
Symptoms:
- Abdominal pain, diarrhea and flatulence (accumulation of
gas) after ingestion of milk / milk-containing products
- >75% of lactose goes unabsorbed toward the colon, where
the bacteria ferment it to short-chain fatty acids, acetate,
butyrate, propionate and hydrogen gas
Etiology:
Primary lactose malabsorption:
- Most common cause is acquired primary lactase deficiency, which is basically the
age-related lactase deficiency
- Congenital lactase deficiency is a rare autosomal recessive disorder infants have
diarrhea from birth (more frequent in the Finnish population)
- Developmental lactose malabsorption is a consequence of prematurity lactase
activity increases in late gestational age
Secondary lactose malabsorption:
- Small intestinal bacterial overgrowth
- Infectious enteritis (e.g. rotavirus)
- Mucosal injuries:
Celiac disease, IBD (especially Crohn’s), drug-induced enteritis, irradiation-
induced enteritis
Diagnosis of lactose intolerance:
1. Presumptive diagnosis:
Mild symptoms occur within a few hours after significant lactose ingestion
and resolve after 5-7 days of avoidance of lactose-containing foods
2. Hydrogen breath test:
Simple, non-invasive and has 80% sensitivity and 98% specificity based on
the bacterial fermentation of lactose in the gut
Oral administration of lactose (2g/kg in children, 50g in adults) hydrogen and
symptom peak occurs at 90-120 min
3. Stool pH:
Especially in infants stool pH <6 after ingestion of milk, with clinical
symptoms presumes lactose intolerance
4. Lactose tolerance test:
Requires repeated blood glucose measurements, has largely been replaced
by lactose breath hydrogen test
Oral administration of lactose, then blood glucose levels are monitored at 0,
60 and 120 minutes low increase (<1,1 mmol/L) in blood glucose plus the
development of symptoms is diagnostic
, KRISTIN FRIBERG (edited by VISHAL KUMAR) 2021/2022
Differential diagnosis:
Cow’s milk allergy (CMA) should be considered in infants and children with
persistent symptoms (severe abdominal pain and massive diarrhea) despite
dietary lactose restriction
Management of lactose intolerance:
Goal is to eliminate symptoms while maintaining Ca2+ and vitamin D intake:
- Dietary lactose restriction (especially milk and ice cream) patients need to be
supplemented with vitamin D and Ca2+
- Enzyme replacement
Commercially available beta-galactosidases can be taken orally with lactose-
containing food
These do not completely hydrolyze all dietary lactose, thus, variable results in
each individual
Celiac disease:
Pathogenesis:
- Autoimmune disorder (prevalence: 1-70 – 1:300)
- Occurs primarily in whites of northern European ancestry
- First-degree relatives of patients have a 10-15% risk of celiac disease
- Prevalence correlates with genetic predisposition (HLA-DQ2 > HLA-DQ8) and high
consumption of gluten containing food
Co-factors are needed: intestinal infections that change the bacterial
population and viral infects that change the immune recognition in the
mucosal wall
Serum auto-antibodies:
- Serum IgA to gliadin (gluten antigen)
- Serum IgA to tTG (tissue transglutaminase): 100% specific!
tTG is an intracellular enzyme released by inflammatory cells and fibroblasts
in response to mechanical irritation or inflammation
Classification of celiac disease:
1. Classic disease:
- Villous atrophy; symptoms of malabsorption (steatorrhea), weight loss or vitamin
deficiency
- Resolution of the mucosal lesions and symptoms within few months upon
withdrawal of gluten-containing foods
- Serum is auto-antibody positive
2. Atypical celiac disease:
- Only minor GI complaints
- May display anemia, osteoporosis, arthritis, increased transaminases
- Mostly with severe mucosal damage and celiac specific auto-antibodies
3. Asymptomatic (silent) celiac disease:
PATHOPHYSIOLOGY FINAL EXAM
1. The pathophysiology of the gastrointestinal system - the diseases of the
stomach and the small intestine
The possible pathomechanism of peptic ulcer and duodenal ulcer; their symptoms and the
principles of treatment
Peptic ulcer disease:
- Peptic ulcers are defects in the GI mucosa extending through the muscular layer
- Can lead to small chronic bleeding which can lead to iron deficiency anemia
Etiology:
- H. pylori infection
- Non-steroidal anti-inflammatory drugs (NSAIDs) (e.g. even chronic low
dose/100mg/Aspirin)
- Viral infections
- Gastrinoma (Zollinger-Ellison syndrome)
- Idiopathic
H. pylori:
- H. pylori tests can be false negative in at least 10% of patients (use of antibiotics and
proton pump inhibitors)
In different locations, it is possible to buy proton pump inhibitors over the
counter patient can mask their symptoms without knowing it
- Ulcer incidence in H. pylori – infected individuals is 6-10x higher than in uninfected
subjects
- H. pylori colonizes the antrum – the lower part of the stomach:
H. pylori produces NH3 in response to the low pH (acidic) more
favorable environment for the bacteria NH3 irritates mucosal
layer to produce even more acid
An ongoing immune response further damages the mucosal layer
hyperacidic response
Diagnosis of H. pylori infection:
Urease activity of H. pylori can be used as diagnostic procedures:
1) Urease breath test
Give carbon-isotope labeled urea to the patient
bacteria cleaves the urea and isotope-labeled CO2 will
be produced measure it from the exhaled air
2) Direct urease test from biopsies or histological evaluation
of them
If we suspect H. pylori infection or the patient has reflux disease perform
esophagoscopy/gastroscopy
,KRISTIN FRIBERG (edited by VISHAL KUMAR) 2021/2022
Chronic NSAID use:
Chronic NSAID use is a common cause of refractory and complicated ulcers:
- Low-dose aspirin (for prevention of thrombotic events) increases risk of GI-bleeding
by 60%
- Proton pump inhibitor use reduces the risk of ulceration it reduces the rate of
ulcer disease in NSAID users at risk
- NSAID in peptic ulcer disease:
NSAIDs will inhibit all types of COX every type of prostaglandin
production will be reduced (PGl usually inhibit acid production) inhibition
of inhibition ↑ acid production
Symptoms and outcomes of peptic ulcer disease:
Symptoms:
- Dyspepsia epigastric pain or discomfort is the most prominent
- Approximately 70% of peptic ulcers are asymptomatic
Complications:
- In 40-50% gastroesophageal reflux disease (GERD)
- Bleeding into the GI-tract ( anemia), rarely hematemesis (vomiting fresh blood)
- In 2-10% perforation of the bowel wall: sudden severe, diffuse abdominal pain
In untreated patients, it usually leads to peritonitis shock death
- Gastric cancer (rare)
The pathophysiology of lactose intolerance and celiac disease; their symptoms,
complications and treatment options
DISEASES OF THE INTESTINES
Leading symptoms:
- Abdominal pain, malabsorption, diarrhea (with or without blood)
- Diarrhea is one of the leading symptoms, because there is a huge daily flow rate in
the intestines minor change in the mucosal layer (e.g. absorption problem) will
lead to several liters fluid loss (= diarrhea)
Lactose intolerance:
- Intolerance to lactose-containing foods
- Most common (>70%) intestinal disease worldwide
- Prevalence is low in children <6 years and increases with age
- Newborns and adults with low lactase activity can adapt to persistent lactose
ingestion through bacterial conversion of lactose to short-chain fatty acids that can
be absorbed in the colon as energy sources
,KRISTIN FRIBERG (edited by VISHAL KUMAR) 2021/2022
Symptoms:
- Abdominal pain, diarrhea and flatulence (accumulation of
gas) after ingestion of milk / milk-containing products
- >75% of lactose goes unabsorbed toward the colon, where
the bacteria ferment it to short-chain fatty acids, acetate,
butyrate, propionate and hydrogen gas
Etiology:
Primary lactose malabsorption:
- Most common cause is acquired primary lactase deficiency, which is basically the
age-related lactase deficiency
- Congenital lactase deficiency is a rare autosomal recessive disorder infants have
diarrhea from birth (more frequent in the Finnish population)
- Developmental lactose malabsorption is a consequence of prematurity lactase
activity increases in late gestational age
Secondary lactose malabsorption:
- Small intestinal bacterial overgrowth
- Infectious enteritis (e.g. rotavirus)
- Mucosal injuries:
Celiac disease, IBD (especially Crohn’s), drug-induced enteritis, irradiation-
induced enteritis
Diagnosis of lactose intolerance:
1. Presumptive diagnosis:
Mild symptoms occur within a few hours after significant lactose ingestion
and resolve after 5-7 days of avoidance of lactose-containing foods
2. Hydrogen breath test:
Simple, non-invasive and has 80% sensitivity and 98% specificity based on
the bacterial fermentation of lactose in the gut
Oral administration of lactose (2g/kg in children, 50g in adults) hydrogen and
symptom peak occurs at 90-120 min
3. Stool pH:
Especially in infants stool pH <6 after ingestion of milk, with clinical
symptoms presumes lactose intolerance
4. Lactose tolerance test:
Requires repeated blood glucose measurements, has largely been replaced
by lactose breath hydrogen test
Oral administration of lactose, then blood glucose levels are monitored at 0,
60 and 120 minutes low increase (<1,1 mmol/L) in blood glucose plus the
development of symptoms is diagnostic
, KRISTIN FRIBERG (edited by VISHAL KUMAR) 2021/2022
Differential diagnosis:
Cow’s milk allergy (CMA) should be considered in infants and children with
persistent symptoms (severe abdominal pain and massive diarrhea) despite
dietary lactose restriction
Management of lactose intolerance:
Goal is to eliminate symptoms while maintaining Ca2+ and vitamin D intake:
- Dietary lactose restriction (especially milk and ice cream) patients need to be
supplemented with vitamin D and Ca2+
- Enzyme replacement
Commercially available beta-galactosidases can be taken orally with lactose-
containing food
These do not completely hydrolyze all dietary lactose, thus, variable results in
each individual
Celiac disease:
Pathogenesis:
- Autoimmune disorder (prevalence: 1-70 – 1:300)
- Occurs primarily in whites of northern European ancestry
- First-degree relatives of patients have a 10-15% risk of celiac disease
- Prevalence correlates with genetic predisposition (HLA-DQ2 > HLA-DQ8) and high
consumption of gluten containing food
Co-factors are needed: intestinal infections that change the bacterial
population and viral infects that change the immune recognition in the
mucosal wall
Serum auto-antibodies:
- Serum IgA to gliadin (gluten antigen)
- Serum IgA to tTG (tissue transglutaminase): 100% specific!
tTG is an intracellular enzyme released by inflammatory cells and fibroblasts
in response to mechanical irritation or inflammation
Classification of celiac disease:
1. Classic disease:
- Villous atrophy; symptoms of malabsorption (steatorrhea), weight loss or vitamin
deficiency
- Resolution of the mucosal lesions and symptoms within few months upon
withdrawal of gluten-containing foods
- Serum is auto-antibody positive
2. Atypical celiac disease:
- Only minor GI complaints
- May display anemia, osteoporosis, arthritis, increased transaminases
- Mostly with severe mucosal damage and celiac specific auto-antibodies
3. Asymptomatic (silent) celiac disease:
