GASTROINTESTINAL TRACT€¦ · Foveolar compartment - uniform through out stomach & consist of: • Surface epithelial cells (Foveolar cells) -lining entire mucosal surface & gastric

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, 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.



Gastic mucosa- two compartments

1. Superficial- Foveolar

(leaf like) compartment

2. Deeper glandular compartment


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.


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


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


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.


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


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.


Erosion & hemorrhage -

Acute erosive Hagic

gastritis.

Erosions - extends

deeply – ulcers


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


• Acid / alkali

ingestion


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….


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).


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


• < 10% of gastritis

• Diffuse mucosal damage to body (fundic area) of stomach

• Spares - antrum

• There is hypergastrinemia.


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)


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)


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


• A, gastric body - deep inflame. infiltrate, of lymphocytes, &

glandular atrophy.

• B, Intestinal metaplasia, goblet cells mixed with foveolar epith


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


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


Clinical features …

B12 deficiency – may cause;

• Atrophic glossitis – smooth and beefy red tongue,

• Malabsorptive diarrhea,

• Neuropathic change;

• Demyelination,

• Axonal degeneration &

• Neuronal death


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.

Thanks

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GASTROINTESTINAL TRACT€¦ · Foveolar compartment - uniform through out stomach & consist of: • Surface epithelial cells (Foveolar cells) -lining entire mucosal surface & gastric