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TRANSCRIPT
GASTROINTESTINAL TRACT
by
DR. BILQUIS
STOMACH
STOMACH (normal anatomy)
Anatomically divided into 5 regions:
1. The Cardia: Surrounded by esophageal sphincter
2. Fundus: Lies against the diaphragm.
3. Body (corpus):
4. Antrum
5. Pylorus (pyloric antrum): Ends at the pyloric sphincter which is a thickening of the muscle walls.
STOMACH (normal anatomy)
• Stomach, opened
along greater curvature.
• Esophagus - at left.
• Antrum
• Pylorus - first portion
of duodenum at lower right.
Endoscopic views;Normal –
• Pylorus at left,
• First portion of duodenum -
right.
STOMACH (normal anatomy)
STOMACH (normal anatomy)
Gastic mucosa- two compartments
1. Superficial- Foveolar
(leaf like) compartment
2. Deeper glandular compartment
STOMACH (normal anatomy)
Foveolar compartment -
uniform through out stomach &
consist of:
• Surface epithelial cells (Foveolar cells) -lining entire mucosal surface & gastric pits.
Foveolar cells:
• Tall col., mucin sec, basal N.
Mucous neck cells – deeper in gastric pits:
• are progenitors of surface epith. cells of gastric glands.
STOMACH (normal anatomy)
Glandular compartment
Is different in thickness & glandular composition in different regions of stomach.
Cardiac glands- contain-
• Mucous sec. cells only
in fundus and body;(acid forming) contain;
• Parietal cells,
• Chief cells &
• Scattered endocrine cells.
Antral or pyloric glands- contain
• Mucous sec. Cells &
• Endocrine cells.
Fundic mucosa
STOMACH (normal anatomy)
Main cell types:
• Mucous cells – cardiac, antral region
• Parietal cells- (bright eosinophilic) -upper ½ of glands in fundus and body
• Chief cells- (basophilic cytoplasm) base of gastric glands
"We make a living by what we get,
but we make a life by what we give.“
Winston Churchill
Gastric pathology
Common pathological lesions:
1. Inflammatory lesions
2. Neoplastic lesions
GASTRITIS: - Inflammation of gastric mucosa - may be :
• Acute Gastritis - Neutrophilic infiltration.
• Chronic Gastritis - Lymphocytes and/or plasma cells,
associated intestinal metaplasia and atrophy.
ACUTE GASTRITIS
‘A transient mucosal inflammatory process may be either’
Mild cases ;
• Asymptomatic or
• Cause variable degree of epigastric pain , nausea and vomiting
• Sever cases-
– Mucosal erosion,
– Ulceration,
– Hemorrhage,
– Hematemesis,
– Melena – may cause major blood loss.
ACUTE GASTRITIS …..
Pathogenesis:
Gastric lumen- acidic, pH: close to 1,
- Helps in digestion , may damage gastric mucosa
Protective mech for gastric mucosa
• Mucin sec by surface foveolar cells, forms a thin layer of mucus that;
1. Prevents large food particles touching the epith
2. Form unstirred layer of fluid on epith
3. has a neutral pH due to bicarbonate ion sec. by surface
epith
• Rich vascular supply to gastric mucosa delivers oxygen, bicarbonates
and nutrients - washing away acid - diffused into lamina propria
• Prostaglandins; Increase sec of Mucin & HCO3, decrease sec of acid,
increase vascular perfusion
Morphology….
ACUTE GASTRITIS ….. Pathogenesis…
Disruption of any of protective mech - increased
susceptibility to acute or chronic gastritis .e.g.;
• Reduced mucin synthesis - in elderly .
• NSAIDS – by; • Blocking prostaglandins or • Reduce bicarbonate secretion,.
• Uremic pts – infected by urease spitting H. Pylori – inhibi gastric bicarb transporters by ammonium.
• High altitudes - decreased oxygen - increased incidence of acute gastritis
ACUTE GASTRITIS …..
Pathogenesis…
• Direct injury - to mucosal epith & stromal cells may be due to;
• Ingestion of acids or bases, (accidentally/ suicidal) –
• Excessive alcohol consumption,
• Radiation, & chemotherapy.
Entire gastric mucosal surface is replaced every 2 - 6 days,
• Mitotic inhibitors, (as in chemotherapy) - generalized mucosal
damage due to insufficient epith regeneration.
ACUTE GASTRITIS …..
Operative influences may be:
• Increased acid secretion
• Decreased production of HCO3 buffer
• Reduced blood flow
• Disruption of adherent Mucus layer
• Direct damage to epith
• Regurgitation of bile acids from duodenum
• Inadequate synthesis of PG’s
Or idiopathic gastritis
ACUTE GASTRITIS …..
MORPHOLOGY
Presence of neutrophils above basement memb in the
epith is abnormal in all parts of GI tract & signifies
active inflam (‘activity’)
• Active inflam - may be present in both acute & chronic
diseases
ACUTE GASTRITIS ….. MORPHOLOGY…
Mild Acute Gastritis:
Surface epith- intact,
Lamina propria –
• Moderate edema &
• Slight V. congestion
• Scattered neutrophils in;
• Surface epith. cells or
• In mucosal glands
L. propria - showing
edema
Scattered neutrophils
ACUTE GASTRITIS ….. MORPHOLOGY…
Severe Acute gastritis ;-
• Hemorrhage – causing
punctate dark spots in
hyperemic mucosa
• Erosion + Hage - Acute
erosive hagic gastritis.
ACUTE GASTRITIS …..
Erosion & hemorrhage -
Acute erosive Hagic
gastritis.
Erosions - extends
deeply – ulcers
ACUTE GASTRITIS …..
MORPHOLOGY…
Severe acute gastritis :
(Erosion + Hage)
• Mucosal erosion ( loss of superficial
epith) causing- defect in mucosa - &
does not cross muscularis mucosa
• Rich neutrophilic infiltrate in mucosa
• Fibrin containing purulent exudate
in lumen
ACUTE GASTRITIS …..
• Acid / alkali
ingestion
ACUTE GASTRITIS …..
Clinical features:
Depending on severity of lesion, acute Gastritis may be;
• Asymptomatic or may cause:
• Epigastric pain
• Nausea & vomiting
• Massive hematemesis ,
• Melena and potentially fatal blood loss
CHRONIC GASTRITIS
CHRONIC GASTRITIS Defined as:
‘Chronic mucosal inflam changes leading eventually to mucosal atrophy and intestinal metaplasia, usually in the absence of erosions’
• Epithelium - dysplastic - lead to carcinoma
Symptoms; - less severe, but more persistent
• Nausea,
• Upper abdominal discomfort
• Sometimes with vomiting
Hematemesis is - uncommon
CHRONIC GASTRITIS….
Causes of ch. gastritis include;
• Bacillus H. pylori Infection. (most common) –
• Autoimmune gastritis – • < 10% of cases of ch. Gastritis • Most common cause in patient without h pylori • Most common cause of atrophic gastritis
• Less common causes : Radiation injury Mechanical injury, Chronic bile reflux and Involvement by systemic diseases –
• Crohn disease,
• Amyloidosis or
• Graft verses host disease
HELICOBACTER PYLORI
GASTRITIS
HELICOBACTER PYLORI
Helicobacter pylori is a :
• Gram- negative, micro aerophilic nonsporing, rods,
• Inhabit various areas of stomach and duodenum.
• Causes - a chronic mild inflam of stomach lining
• > 80% of infected individuals -
asymptomatic.
HELICOBACTER PYLORI GASTRITIS
• Spiral shaped or curved bacilli - seen in biopsy specimens of;
• All duodenal ulcers and
• Majority of gastric ulcers / ch. gastritis
• Acute H. pylori infection – no symptom
• Ch. Infection – need treatment
H. PYLORI GASTRITIS
• > 50% of world's population - H. pylori in upper GI tract.
• Infection –
• More prevalent in developing countries,
• May lead to-
• Peptic ulcer disease,
• Increased risk of gastric ca.
H.PYLORI contd… H. pylori —
• use their spiral shape and
flagella to move through
mucus covering of stomach,
• This mucus - protects bacteria against the effects of acids.
• Routes of infection
• Oral – oral,
• Fecal – oral, and
• Environmental spread
H. pylori Virulence include:
Flagella; - allow the bacteria to be motile
in viscous mucus
Urease ;- produces ammonia from
endogenous urea, - buffering gastric acid by elevating local gastric pH in vicinity of organism
Adhesins; - enhances bacterial adherence
to surface foveolar cells
Toxins ; -such as;
Cytotoxin association gene A (cagA) &
Vaculating cytotoxin gene A (VacA)
H.PYLORI contd… The protective mucus layer of the stomach:
• H. pylori - produced urease,
degrades urea to produce
bicarbonate and ammonia.
• The ammonia neutralizes acid in the
area, increasing pH in the mucus to
about 7.
• Ammonia - toxic to lining cells +
other toxins, cells die / get
inflammed .
H. PYLORI GASTRITIS
PATHOGENESIS:
• In high prevalence areas Infection acquired > in children
– persist for decades, explaining direct coorrelation
between colonization rate and patient age
• Damage done due to;
• Infection result in increase acid production
• Imbalance between gastro - duodenal mucosal defense and
damaging forces
H.PYLORI contd…
• Present as; –
• Antral gastritis with high acid production despite
hypogastrinemia
• Occasionally involve Cardia
• Gastritis - may progress to gastric body & fundus –
PAN GASTRITIS ass. with;
• Multifocal mucosal atrophy,
• Reduced acid secretion,
• Intestinal metaplasia and
• Increased risk of gastric Adeno ca
Progression to pan gastritis • Host factor
• Interaction btw host n bacterium seems critical
• Particular Polymorphism in gene encoding • Proinflammatory cytokine IL-1B
• TNF
• Variety of other genes
• Coorrelate with development of pan gastrtitis
• Genetic variation of h.pylori • Also influence seeverity of diesease
• CagA gene (marker for pathogenicity island of almost 20 genes present in
• 50% isolates overall
• 90% h pylori isolates in population with elevated gastric cancer risk
H.PYLORI contd…
80 % of pts with duodenal ulcers - infected by cytotoxin
– associated antigen (Cag A) positive strains & cause;
• More severe epith. damage
• Acute & chronic inflam.
• > Chance of peptic ulceration
• Increase risk of gastric ca.
Morphology:
• H. Pylori (tropism for gastric mucosa) present in ass with;
• Gastric mucosa
• Chronically injured duodenum with pyloric metaplasia
• Gastric type mucosa in Barrett esophagus
Not generally found in association with gastric intestinal
metaplasia or duodenum epithelium
• In stomach, H. Pylori are found in antrum > cardia.
• Antral biopsy is preferred for evaluation of H. pylori gastritis
H. PYLORI GASTRITIS….
H. PYLORI GASTRITIS….
On Endoscopic Examination:
H. pylori infected antral mucosa ;
• Erythematous ,
• Coarse / nodular
(nodular gastropathy).
H.PYLORI GASTRITIS
Distribution of h.pylori
• Superficial mucus oberlying epithelium in surface and neck regions
• Distribution can be irregular with areas of heavy colonization adjacent to those with few organisms
• In extreme cases • Organism carpets luminal surfaces of foveolar and
mucous neck cells
• Can even extend into gastric pits
H. PYLORI GASTRITIS
Morphology…
• Neutrophils in lamina propria
• Some cross basement membrane to
assume and intraepithelial location and
accumulates in lumen of gastric pits – pit
abscesses
• in addition superficial lamina propria
contain
• Plasma cells (large number often in sheets
or clusters
• Lymphocytes n macrophages (in increase
numbers
Intraepith neutrophils & sub epith
plasma cells – ch. of H. Pylori gastritis
Neutrophils
infiltrating foveolar epith in
active H. pylori gastritis.
H. PYLORI GASTRITIS
• Chronic gastritis, showing;
• Partial intestinal metaplasia (upper left), and
• Inflam of lamina p. containing lymphocytes & plasma cells (right).
H. PYLORI GASTRITIS….
Morphology…
In extreme cases –
• Organisms carpet the luminal
surfaces of foveolar and mucus
neck cells –
• Can extend – gastric pits
An antral gland of stomach with a
Giemsa-stained colony of H.
pylori in lumen
H. PYLORI GASTRITIS
H. pylori gastritis.
• A Steiner silver stain
• Organisms along luminal surface of gastric epith cells.
• No tissue invasion by bacteria (may invade but not evident histologically & contribution of invasion to disease not known)
H. PYLORI GASTRITIS
Morphology…
When intense
Inflamatory infltrates may create
thickened rugal folds mimicking
early infiltrative lesions
Long standing infection –
• May involve - body & fundus.
Mucosa – atrophic
• Lymphoid aggregates, some
with germinal centers
oRepresent mucosa
associated lymphoid tissue
or MALT-
oPotential to transform in to
lymphoma.
H. PYLORI GASTRITIS Clinical Features
Usually causes few symptoms
• Nausea
• Vomiting
• Upper abdominal Discomfort- burning pain
With advanced disease - pt. has;
• Hypochlorhydria - due to parietal cell loss & (not achlorhydia)
• Mucosal atrophy of body and fundus
(in hpylori its not severe => dis occurs in autoimmune gastritis )Severe
parietal cell loss – hypo / achlorhydria & hypergastrinemia – present as-
Gastritis → Peptic ulcer →gastric ca
Diagnostic Tests for H. pylori
Non invasive tests:
• Serological tests for H.pylori antibodies
• Fecal bacterial detection
• Urea breath test (based on generation of ammonia by bacterial ureaese)
Invasive tests:
• Identification of H. pylori in Gastric biopsy tissue by;
– Microscopy,
– Bacterial culture,
– Rapid urease test
• Bacterial DNA detection by PCR
Treatment
• Antibiotics + ppi
• Improvement , chances of relapses if incomplete eradication or reinfection
• Prophylactic n therapeutic vaccine in early stage of development
• Complication : peptic ulcer
Autoimmune gastritis
Autoimmune gastritis
• < 10% of gastritis
• Diffuse mucosal damage to body (fundic area) of stomach
• Spares - antrum
• There is hypergastrinemia.
Autoimmune gastritis
Characterized by:
• Auto antibodies against;
• Parietal cells,
• Gastrin receptors and
• Intrinsic factor, -
Can be detected in serum and gastric secretion.
• Reduced serum pepsinogen -1 conc.
• Endocrine cell hyperplasia - Antrum
• Vitamin B 12 deficiency
• Defective gastric acid secretion (achlorhydria)
Autoimmune gastritis
Pathogenesis
• Loss of parietal cells - decreased sec. of;
• Gastric acid and
• Intrinsic factor
• Absence of acid production – stimulates gastrin release –
• Hyper - gastrinemia and
• Hyperplasia of antral gastrin producing G cells
Autoimmune gastritis Pathogenesis
• ↓ intrinsic factor →disables ileal - B12 absorption → B12
deficiency and megaloblastic anemia
• Chief cell destruction → Reduced serum pepsinogen -1
conc.
If autoimmune destruction - controlled by immuno
suppression – glands can repopulate indicating gastric
stem cells not affected
Autoimmune gastritis cont…
Morphology; Ch. by:
• Diffuse mucosal damage of the oxyntic mucosa within fundus and body
• Damage to cardiac and antrum typically absent or mild
• With diffuse atrophy, Mucosa of body and fundus appears markedly thinned and rugal folds lost
• Severe B12 deficiency – enlargement of epith. nuclei – (megaloblastic
change)
• Lymphocytes, macrophages and plasma cells - deep & centered on gastric glands. (Neutrophils may be present)
Autoimmune gastritis cont…
Morphology…
• When atrophy incomplete –residual mucosa - polyp /
nodules.
• Small surface elevations – correlate with intestinal
metaplasia(columnar absorbtive cells and goblet cells)
• Decreased acid production - antral endocrine cell
hyperplasia - proportional to degree of mucosal atrophy
• Difficult to appreciate on h&e for ecl (enterochromaffin like) cells
not easily recognized
• Over the time – hyper gastrinemia ;-
• Stimulates endocrine cell hyperplasia in fundus & body –
• May progress to small, multicentric, low grade, neuroendocrine
/ carcinoid tumors
Autoimmune gastritis cont…
• A, gastric body - deep inflame. infiltrate, of lymphocytes, &
glandular atrophy.
• B, Intestinal metaplasia, goblet cells mixed with foveolar epith
Autoimmune gastritis cont…
Clinical features:
• Antibodies to parietal cells and intrinsic factor are
present in early phase of disease
• Progression to gastric atrophy – over 2-3 decades
• Due to slow onset and variable progression median age at
diagnosis- 60 yrs
• Women > men
Autoimmune gastritis cont…
Clinical features:
• P. anemia & autoimmune gastritis –often ass. with other
autoimmune diseases as-
• Hashimotos thyroiditis,
• Insulin dependent diabetes mellitus,
• Addison's disease,
• Graves disease,
• Genetic predisposition - 20% of relatives of pts with
p.anemia also have - autoimmune gastritis
Autoimmune gastritis cont…
Clinical features …
B12 deficiency – may cause;
• Atrophic glossitis – smooth and beefy red tongue,
• Malabsorptive diarrhea,
• Neuropathic change;
• Demyelination,
• Axonal degeneration &
• Neuronal death
Autoimmune gastritis cont…
Clinical features …
B12 deficiency ….
• Peripheral neuropathy – paresthesias and numbness
• Spinal cord lesions – loss of - vibration and position sense, limb
weakness & spasticity
• Cerebral manifestations - range from mild personality changes
and memory loss to psychosis
Characteristis of H.pylori - associated and autoimmune gastritis
H. Pylori - associated Autoimmune
Location Antrum Body
Inflammatory
infiltrate
Neutrophils,
Sub epithelial plasma cells Lymphocytes, macrophages
Acid
production Increased / slightly decreased Decreased
Gastrin Normal to decreased Increased
Other lesions Hyperplastic / inflmmatory
polyps Neuroendocrine hyperplasia
Serology Antibodies to H. Pylori Antibodie to prietal cells ( intrinsic factor)
Sequelae Peptic ulcer ,
Adeno carcinoma
Atrophy, pernicious anemia, Adeno ca.,
carcinoid tumor
Associations Low socioeconomic status,
residence in rural areas
Autoimmune disease; thyroiditis,
diabetese mellitis, graves disease
Sydney System of Grading Chronic Gastritis
1. Site: Antral, Corporal mucosa
2. Grading of: (Mild, Moderate, Marked)
H-Pylori
Chronic inflammation
Activity
Atrophy
Intestinal metaplasia
*Normal lymphocytes & plasma cells in lamina propria
- up to 5/HPF
*No Neutrophils in lamina propria
Uncommon forms of gastritis
1-Reactive Gastropathy
• Etiology –
– Chemical injury , aspirin ,
NSAIDS, bile reflux and
mucosal trauma
Endoscopy;
- longitudinal stripes of edematous
& erythmatous mucosa - alternating
with less severely injured mucosa –
(water melon stomach)
1-Reactive Gastropathy…
Histologically;
Antral mucosa shows ;
• Foveolar hyperplasia ,
• Glandular regenerative changes
• Mucosal edema &
• Dilated capillaries containing
fibrin thrombi.
• Imp. Feature for diagnosis -
absence of neutrophils in the epith.
2. Eosinophilic
Gastritis:
An idiopathic condition ch.by; • Tissue damage & • Dense Eosinophilic infiltrate of
mucosa, & muscularis Site:
• Antral / pyloric region ,
• Other areas of GI tract often
involved
Causes: Allergic reactions to; • Cows milk • Soy protein, • Drug allergy – • Parasitic infections and • H. pylori infection
3. LYMPHOCYTIC GASTRITIS:
• > in women
• Site; body of stomach
• Symptoms: abdominal pain, anorexia, nausea & vomiting.
• 40% - associated with celiac disease – immune mediated
• Endoscopy: - thick fold covered by small nodules with central Aphthous ulceration
3. LYMPHOCYTIC
GASTRITIS…
Histologically –
Markedly increased
intraepith lymphocyte -
mucosal surface and gastric
pits
4. Granulomatous Gastritis: Any gastritis with granulomas or
aggregates of epitheloid histiocytes
• Diagnosis by;
correlation of clinical, endoscopic,
radiological and serologic data
• Gastric involvement by;
– Crohn disease,
– Sarcoidosis,
– Infections - mycobacterium,
fungi, CMV, and H. pylori.
• Narrowing & rigidity of gastric
antrum due to transmural
granulomatous inflammation
Granulomatous chronic gastritis.
Noncaseating granulomas in the
lamina propria.
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