Autoimmune Atrophic Gastritis

Slide 1 · Autoimmune atrophic gastritis

Gastric immune injury • oxyntic atrophy • systemic consequences

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Diagnostic signature

Corpus/fundus-predominant destruction of acid-producing oxyntic glands.

Antral sparing, achlorhydria, hypergastrinemia, and endocrine proliferation.

Intrinsic factor deficiency links gastric injury to vitamin B₁₂ deficiency.

Body + fundus

Oxyntic glands / parietal cells

Main autoimmune target

Antrum

G cells • typically relatively spared

Functional region map — schematic

Slide 3 · Learning outcomes

Explain the immune targets and why oxyntic atrophy develops.

Connect acid and intrinsic factor loss to laboratory and clinical sequelae.

Identify the characteristic morphology and distinguish H. Pylori gastritis.

Recognize the two principal neoplastic associations.

Slide 4 · Stomach regions have distinct gland populations

Body and fundus contain well-developed oxyntic glands.

Antral glands contain hormone-producing G cells.

This functional compartmentalization explains the selective lesion pattern.

Body + fundus

Oxyntic glands / parietal cells

Main autoimmune target

Antrum

G cells • typically relatively spared

Functional region map — schematic

Slide 5 · Oxyntic glands: Secretory specialization

Parietal cells provide gastric acid and intrinsic factor.

Chief cells produce pepsinogen (digestive enzyme precursor).

Both cell populations are depleted as autoimmune oxyntic atrophy progresses.

Intact oxyntic mucosa

Atrophic oxyntic mucosa

Simplified gland architecture; Not an H&E image

Slide 6 · Antral G cells respond to gastric acid loss

Antral G cells secrete gastrin, stimulating parietal-cell acid production.

Loss of acid removes an important physiological negative-feedback signal.

Compensatory gastrin release persists despite low acid output.

Oxyntic acid production ↓

Acid feedback ↓

Gastrin secretion ↑

Mechanistic sequence — schematic

Slide 7 · Disease definition: Immune-mediated oxyntic atrophy

Autoimmune inflammation progressively damages gastric body and fundus.

The defining structural endpoint is loss of parietal and chief cells.

Functional and epithelial changes arise from the missing gland populations.

Intact oxyntic mucosa

Atrophic oxyntic mucosa

Simplified gland architecture; Not an H&E image

Slide 8 · Classic topography separates two gastritides

Autoimmune gastritis: Body/fundus predominant, antrum usually spared.

H. Pylori gastritis: Commonly antral and superficially inflamed.

Distribution is highly informative but should not be treated as an absolute exclusion rule.

Autoimmune

Body / fundus

Oxyntic loss

H. Pylori

Antrum often affected

Superficial inflammation

Characteristic patterns — not exclusive criteria

Slide 9 · Frequency and typical diagnostic age

Less than 10% of chronic gastritis cases estimate.

Estimated prevalence: 2% among adults older than 60 years.

Median age at clinical diagnosis: Approximately 60 years.

<10%

Chronic gastritis cases

2%

Persons >60 years

60 years

Median age at diagnosis

Slide 10 · Demographic and autoimmune context

Females are affected slightly more often than males.

The disorder may coexist with autoimmune thyroid, pancreatic, or adrenal disease.

Clinical presentation often follows a long subclinical course.

Hashimoto

Thyroiditis

Type 1

Diabetes mellitus

Addison

Disease

Family

Clustering

Associations; Not diagnostic criteria

Slide 11 · Familial aggregation suggests predisposition

Familial clustering has been observed.

Concordance in some monozygotic twins supports inherited susceptibility.

The textbook does not identify established responsible genetic variants.

Slide 12 · Primary autoantigen: The gastric proton pump

The H⁺/K⁺-ATPase of parietal cells is a major immune target.

The membrane pump is required for hydrogen ion secretion.

Loss of pump-bearing cells leads directly to impaired acidification.

H⁺/K⁺-ATPase antigen

Immune targeting

Parietal-cell injury

Acid secretion ↓

Mechanistic sequence — schematic

Slide 13 · CD4⁺ T cells participate in gland injury

CD4⁺ T cells as principal agents of injury.

The associated inflammation is centered deep around oxyntic glands.

Persistent immune attack can culminate in marked glandular atrophy.

CD4⁺-driven autoimmune response

Gland-centered inflammation

Oxyntic cell destruction

Mechanistic sequence — schematic

Slide 14 · Anti-parietal cell antibodies: Diagnostic clue

Antibodies recognize parietal-cell components, including H⁺/K⁺-ATPase.

They may be found in serum and gastric secretions.

Positive serology supports the diagnosis when matched to anatomy and morphology.

Slide 15 · Anti-intrinsic factor antibodies: Parallel clue

Autoantibodies to intrinsic factor can accompany anti-parietal cell antibodies.

The antibodies may precede overt gastric atrophy and pernicious anemia.

Absence of one antibody does not by itself settle the histologic diagnosis.

Target 1

Parietal-cell H⁺/K⁺-ATPase

Oxyntic cell injury

Target 2

Intrinsic factor

B₁₂ deficiency context

Characteristic patterns — not exclusive criteria

Slide 16 · Serology can precede tissue injury by decades

Anti-parietal cell and anti-intrinsic factor antibodies may precede complications.

Textbook interval: Approximately 2–3 decades before atrophy and pernicious anemia.

A positive antibody result is not synonymous with established end-stage disease.

Antibodies appear

Serologic phase

Years to decades

Slow progression

Oxyntic atrophy

Anatomic lesion

B₁₂ sequelae

Clinical phase

Possible lag: ~2–3 decades (textbook description)

Slide 17 · Loss of oxyntic glands integrates the disease

Immune injury progressively removes parietal and chief cells.

Inflammatory and replacement epithelial changes remodel the gastric mucosa.

Structural atrophy generates the downstream endocrine and nutritional phenotype.

Intact oxyntic mucosa

Atrophic oxyntic mucosa

Simplified gland architecture; Not an H&E image

Slide 18 · The distribution is anatomically selective

Diffuse damage concentrates in acid-producing body and fundus mucosa.

The antrum and cardia are typically relatively spared.

Biopsy site identification is therefore part of histologic interpretation.

Body + fundus

Oxyntic glands / parietal cells

Main autoimmune target

Antrum

G cells • typically relatively spared

Functional region map — schematic

Slide 19 · Why achlorhydria occurs

Gastric acid secretion depends on surviving functional parietal cells.

Diffuse depletion reduces acid production, often to achlorhydria.

Acid output is low despite the compensatory rise in gastrin.

Parietal-cell mass ↓

Hydrogen ion secretion ↓

Achlorhydria

Mechanistic sequence — schematic

Slide 20 · Low acid drives hypergastrinemia

Reduced luminal acid is sensed by the gastrin-regulatory system.

Antral gastrin release increases after loss of acid inhibition.

Marked hypergastrinemia is a characteristic biochemical feature.

Acid production ↓

Negative feedback ↓

Serum gastrin ↑↑

Mechanistic sequence — schematic

Slide 21 · Antral G-cell hyperplasia is compensatory

G cells are located in the relatively preserved antrum.

Persistent stimulation increases antral G-cell numbers.

G-cell hyperplasia differs from the oxyntic gland destruction in the corpus.

Antrum

G-cell response

Hyperplasia

Corpus

Parietal cells lost

Achlorhydria

Characteristic patterns — not exclusive criteria

Slide 22 · Hypergastrinemia stimulates endocrine cells

Gastrin has trophic effects on gastric endocrine populations.

Endocrine and enterochromaffin-like (ECL) cell hyperplasia is common.

This is a proliferative consequence of impaired gastric acid production.

Achlorhydria

Gastrin ↑

ECL cell hyperplasia

Mechanistic sequence — schematic

Slide 23 · ECL hyperplasia creates a tumor pathway

Diffuse endocrine hyperplasia may be seen within the atrophic corpus.

Occasionally, it progresses to multiple small, low-grade gastric NETs.

These lesions are biologically distinct from metaplasia-associated adenocarcinoma.

Persistent hypergastrinemia

ECL hyperplasia

Small multifocal low-grade NETs (rare)

Mechanistic sequence — schematic

Slide 24 · Intrinsic factor is lost with parietal cells

Intrinsic factor is normally secreted by parietal cells.

Oxyntic destruction compromises intrinsic factor availability.

This produces a malabsorptive mechanism independent of dietary B₁₂ intake.

Parietal-cell loss

Intrinsic factor ↓

B₁₂ uptake impaired

Mechanistic sequence — schematic

Slide 25 · Vitamin B₁₂ requires intrinsic factor

Intrinsic factor enables vitamin B₁₂ absorption in the ileum.

Deficiency of intrinsic factor interrupts that absorptive pathway.

The resulting deficiency becomes clinically evident over time.

Dietary vitamin B₁₂

Intrinsic factor dependent uptake

Ileal absorption

Systemic B₁₂ status

Mechanistic sequence — schematic

Slide 26 · Pernicious anemia: The hematologic endpoint

Intrinsic factor deficiency produces vitamin B₁₂ malabsorption.

Sustained deficiency leads to megaloblastic anemia.

Pernicious anemia is a clinical complication, not a synonym for every early autoimmune lesion.

Intrinsic factor deficiency

Vitamin B₁₂ deficiency

Megaloblastic anemia

Mechanistic sequence — schematic

Slide 27 · Serum pepsinogen I is reduced

Oxyntic glands contribute to pepsinogen I production.

Loss of oxyntic gland mass accompanies reduced serum pepsinogen I.

This is a biochemical correlate of corpus glandular atrophy.

Oxyntic glands lost

Pepsinogen I ↓

Supports corpus atrophy

Mechanistic sequence — schematic

Slide 28 · Functional biomarker pattern reflects cell loss

Low acid secretion is a direct consequence of parietal-cell depletion.

Elevated gastrin is a homeostatic response to low acid.

Low pepsinogen I is a correlate of oxyntic gland loss.

Autoantibodies support an autoimmune cause of the tissue damage.

Antibodies

Immune association

Gastrin ↑

Acid feedback loss

Pepsinogen I ↓

Oxyntic gland loss

Acid ↓

Parietal-cell loss

Slide 29 · Two consequences of one destructive lesion

Parietal-cell loss branches into acid deficiency and intrinsic factor deficiency.

Acid deficiency drives gastrin and ECL proliferation.

Intrinsic factor deficiency produces a vitamin B₁₂–dependent multisystem illness.

Autoimmune oxyntic

Parietal-cell loss

Acid production ↓

Gastrin ↑ → ECL hyperplasia

Intrinsic factor ↓

Vitamin B₁₂ deficiency → anemia

Two distinct consequences — schematic

Slide 30 · Gross morphology: Advanced oxyntic thinning

The corpus and fundic mucosa may become markedly thinned.

Normal rugal folds are progressively reduced or lost.

The antrum may appear comparatively preserved.

Normal rugal contours

Atrophic corpus: Flatter folds

Conceptual surface contour; Not an endoscopic image

Slide 31 · Incomplete atrophy may produce pseudopolyps

Islands of surviving oxyntic mucosa may stand above atrophic surroundings.

The resulting appearance can resemble numerous small polyps or nodules.

Endoscopic elevation does not automatically imply a neoplasm.

Residual oxyntic islands surrounded by atrophy — schematic

Slide 32 · Metaplastic foci can form small elevations

Focal surface prominences may correspond to intestinal metaplasia.

These foci replace normal gastric differentiation with intestinal-type cells.

Gross appearances require correlation with targeted mucosal biopsy.

Goblet cell

Illustration of cell phenotype; Not a histologic specimen

Slide 33 · The chronic infiltrate is mononuclear

Lymphocytes, macrophages, and plasma cells predominate.

Lymphoid aggregates and follicles may accompany the infiltrate.

Prominent neutrophilic activity is not characteristic of pure autoimmune gastritis.

Surface epithelium

Deep mononuclear infiltrate

Simplified mucosal architecture — schematic

Slide 34 · Inflammation centers on deeper glands

Autoimmune inflammatory injury is centered within deep oxyntic mucosa.

Lymphocytes contact and damage the glandular compartment.

This differs from the superficial emphasis of typical H. Pylori gastritis.

Surface epithelium

Deep mononuclear infiltrate

Simplified mucosal architecture — schematic

Slide 35 · Superficial versus deep inflammation matters

H. Pylori gastritis often shows superficial plasma-cell-rich inflammation.

H. Pylori can show epithelial neutrophils and pit abscesses.

Autoimmune gastritis favors deeper lymphocyte/macrophage-rich gland injury.

H. Pylori

Superficial lamina propria

Neutrophilic activity

Autoimmune

Deep oxyntic glands

Mononuclear injury

Characteristic patterns — not exclusive criteria

Slide 36 · Histology: Parietal and chief cells disappear

Oxyntic glands lose their characteristic parietal-cell component.

Chief cell loss may be extensive as gland numbers decrease.

Replacement epithelium and stromal inflammation alter normal gland architecture.

Intact oxyntic mucosa

Atrophic oxyntic mucosa

Simplified gland architecture; Not an H&E image

Slide 37 · Partial involvement leaves uneven gland islands

Residual oxyntic glands can persist within extensive atrophic mucosa.

The architecture may be patchy before complete destruction.

Tissue sampling can therefore influence how much atrophy is represented.

Intact oxyntic mucosa

Residual gland islands

Simplified gland architecture; Not an H&E image

Slide 38 · Intestinal metaplasia is recognizable by goblet cells

The surface and gland epithelium may acquire intestinal differentiation.

Goblet cells are the key morphologic clue.

Metaplastic glands replace a portion of the former gastric mucosa.

Goblet cell

Illustration of cell phenotype; Not a histologic specimen

Slide 39 · Other intestinal-type cells may accompany metaplasia

Metaplastic epithelium may also contain absorptive cells.

Paneth cells can appear in some intestinalized gastric mucosa.

The replacement cell phenotype documents altered epithelial differentiation.

Goblet cell

Illustration of cell phenotype; Not a histologic specimen

Slide 40 · Endocrine proliferation is a separate histologic clue

Hyperplasia of endocrine and ECL cells commonly accompanies atrophy.

This finding reflects sustained gastrin stimulation.

It should not be conflated with the presence of an established NET.

Atrophic corpus glands

Gastrin signal

ECL cell foci

Schematic endocrine response, not IHC

Slide 41 · Severe B₁₂ deficiency affects the epithelium

Deficiency can cause enlarged epithelial nuclei (megaloblastic change).

This is a systemic nutritional consequence expressed in a rapidly dividing mucosa.

It is not the primary mechanism of parietal-cell destruction.

B₁₂ deficiency

Abnormal nuclear maturation

Epithelial nuclear enlargement

Mechanistic sequence — schematic

Slide 42 · A characteristic biopsy constellation

Body/fundus: Prominent oxyntic gland loss with deep chronic inflammation.

Associated intestinal metaplasia and endocrine-cell hyperplasia.

Antrum relatively preserved; Neutrophils usually not prominent.

✓

Corpus-predominant gland loss

✓

Deep chronic infiltrate

✓

Intestinal metaplasia

✓

ECL hyperplasia

Slide 43 · Correct site labeling strengthens interpretation

Interpret body/fundus biopsy findings in light of native oxyntic glands.

Compare antral findings rather than assuming diffuse pan-gastric injury.

Location, gland phenotype, and inflammation must be read together.

Body + fundus

Oxyntic glands / parietal cells

Main autoimmune target

Antrum

G cells • typically relatively spared

Functional region map — schematic

Slide 44 · Serology supports—not replaces—morphology

Anti-parietal cell and anti-intrinsic factor antibodies support an autoimmune process.

Antibodies may be detected long before histologic atrophy or anemia.

A concordant corpus-predominant pattern provides the necessary tissue context.

Serology

Etiologic support

Can precede lesions

Biopsy

Anatomic pattern

Demonstrates atrophy

Characteristic patterns — not exclusive criteria

Slide 45 · Antibody frequencies: Avoid overinterpretation

Anti-pump/intrinsic factor antibodies in up to 80% of patients.

This is a grouped statement; It does not establish equal performance for both assays.

Negative serology does not erase a characteristic injury pattern.

Up to 80%

Reported antibody presence

2–3 decades

Possible preclinical lead time

No fixed cutoff

Source gives no diagnostic threshold

Slide 46 · Hypergastrinemia has a mechanistic explanation

The stomach can produce high gastrin while still secreting little acid.

Loss of parietal-cell mass is the limiting lesion.

ECL hyperplasia is a tissue correlate of the endocrine response.

Corpus atrophy

Acid ↓

Gastrin ↑

ECL hyperplasia

Mechanistic sequence — schematic

Slide 47 · Reduced pepsinogen I points toward oxyntic loss

Chief-cell depletion accompanies loss of body/fundic glands.

Lower pepsinogen I reflects reduced secretory gland mass.

The marker as characteristic, not a standalone diagnostic test.

Slide 48 · The major manifestations reflect B₁₂ deficiency

The clinical syndrome can involve bone marrow, oral mucosa, intestine, and nervous system.

Symptoms need not be confined to epigastric discomfort.

The gastric autoimmune process explains the systemic findings.

Bone marrow

Megaloblastosis

Oral mucosa

Atrophic glossitis

Intestine

Malabsorptive diarrhea

Spinal cord

Subacute combined degeneration

Slide 49 · Megaloblastic anemia results from deficient B₁₂

Intrinsic factor loss impairs B₁₂ absorption in the terminal ileum.

Hematopoietic precursors develop megaloblastic maturation abnormalities.

Anemia can become a presenting feature of previously unrecognized gastric disease.

Intrinsic factor loss

B₁₂ malabsorption

Megaloblastic hematopoiesis

Pernicious anemia

Mechanistic sequence — schematic

Slide 50 · Atrophic glossitis is a mucosal signal

Deficient B₁₂ can result in a smooth, beefy-red tongue.

The loss of papillary texture is termed atrophic glossitis.

This supports the clinical link between stomach pathology and epithelial turnover.

B₁₂ deficiency

Oral epithelial changes

Smooth, red tongue

Mechanistic sequence — schematic

Slide 51 · Intestinal symptoms can accompany deficiency

Malabsorptive diarrhea among clinical manifestations.

Epithelial megaloblastosis helps link cellular dysfunction and symptoms.

The presence or absence of diarrhea does not define the gastric histologic pattern.

Slide 52 · Neurologic consequences require recognition

Vitamin B₁₂ deficiency can involve the central nervous system.

Subacute combined degeneration of the spinal cord is a major example.

A clinical assessment limited to hemoglobin can miss neurologic involvement.

Intrinsic factor loss

B₁₂ deficiency

Spinal cord injury

Mechanistic sequence — schematic

Slide 53 · Associated autoimmune disorders are a clue

Hashimoto thyroiditis is a frequent named association.

Type 1 diabetes mellitus and Addison disease are also documented.

A multisystem autoimmune history increases the relevance of the gastric pattern.

Hashimoto

Thyroiditis

Type 1

Diabetes mellitus

Addison

Disease

Family

Clustering

Associations; Not diagnostic criteria

Slide 54 · Comparison: Injury site and cell infiltrate

Topography and depth of inflammation provide the first discriminators.

The table summarizes the characteristic textbook patterns, not absolute rules.

Feature

H. pylori-associated

Autoimmune

Predominant site

Antrum

Body / fundus

Inflammatory pattern

Neutrophils; superficial plasma cells

Lymphocytes, macrophages; deep injury

Acid output

Increased to slightly decreased

Decreased

Gastrin

Normal to increased

Increased to markedly increased

Slide 55 · Comparison: Markers and clinical sequelae

Etiologic markers and end-organ outcomes help refine a morphologic differential.

Both chronic inflammatory conditions may carry gastric cancer risk.

Feature

H. pylori-associated

Autoimmune

Serology

Anti–H. pylori

Anti-parietal cell / anti-IF

Other lesion

Inflammatory / hyperplastic polyps

ECL / endocrine hyperplasia

Characteristic sequel

Peptic ulcer; MALT lymphoma

Atrophy; pernicious anemia; NET

Autoimmunity

Not a defining association

Thyroiditis, type 1 diabetes, etc.

Slide 56 · Cancer risk follows chronic atrophy and metaplasia

Chronic oxyntic atrophy is frequently associated with intestinal metaplasia.

Intestinal metaplasia is strongly associated with gastric adenocarcinoma risk.

Particularly high risk in autoimmune metaplastic atrophy.

Chronic gland loss

Intestinal metaplasia

Increased adenocarcinoma risk

Mechanistic sequence — schematic

Slide 57 · Adenocarcinoma and NET arise by distinct routes

Epithelial intestinal metaplasia is associated with adenocarcinoma risk.

Gastrin-driven ECL cell proliferation can lead to low-grade NETs.

Both consequences occur in the same autoimmune atrophic setting.

Autoimmune oxyntic atrophy

Intestinal metaplasia

Adenocarcinoma risk ↑

Hypergastrinemia → ECL hyperplasia

Low-grade gastric NET risk

Associated pathways; Neither outcome is inevitable

Slide 58 · Avoid a diagnostic shortcut

Antibody positivity alone does not establish the extent of gastric atrophy.

Marked gastrin elevation must be interpreted alongside acid-secretory context.

A biopsy showing goblet cells must still be localized within the stomach.

✓

Corpus-predominant gland loss

✓

Deep chronic infiltrate

✓

Intestinal metaplasia

✓

ECL hyperplasia

Slide 59 · Teaching case: Anemia with autoimmune history

Hypothetical patient: 61-year-old woman with fatigue and a history of Hashimoto thyroiditis.

Laboratory evaluation reveals vitamin B₁₂ deficiency and parietal-cell antibodies.

Biopsies show body-predominant oxyntic gland loss with relative antral preservation.

Question: Identify the unifying gastric process and explain the anemia.

Hypothetical teaching case

Correlate anatomy + serology + function

Slide 60 · Case interpretation: Two linked deficiencies

The anatomic distribution and autoantibodies support autoimmune atrophic gastritis.

Parietal-cell loss leads to intrinsic factor deficiency.

Ileal B₁₂ malabsorption explains the pernicious-anemia phenotype.

Autoimmune oxyntic atrophy

Intrinsic factor ↓

Ileal B₁₂ uptake ↓

Megaloblastic anemia

Mechanistic sequence — schematic

Slide 61 · Teaching case: Hypergastrinemia without acid

Hypothetical patient: Body/fundus atrophy, little gastric acid secretion, markedly elevated gastrin.

Biopsy demonstrates endocrine-cell hyperplasia in the atrophic corpus.

Question: Why does gastrin rise when gastric acid remains low?

Hypothetical teaching case

Correlate anatomy + serology + function

Slide 62 · Case interpretation: Feedback cannot restore glands

Loss of acid suppresses the normal inhibitory feedback on gastrin release.

G cells increase gastrin secretion, but the target parietal-cell mass is depleted.

Gastrin continues to stimulate ECL cells, creating a NET-predisposing milieu.

Parietal cells lost

Acid ↓ → Gastrin ↑

ECL hyperplasia

Rare low-grade NET

Mechanistic sequence — schematic

Slide 63 · Histopathology synthesis

Identify the oxyntic site and the deep, gland-centered chronic infiltrate.

Evaluate the degree of parietal/chief cell loss and intestinal metaplasia.

Recognize endocrine hyperplasia, usually preserved antrum, and the clinical B₁₂ context.

Contrast with superficial, often neutrophilic H. Pylori gastritis.

✓

Corpus-predominant gland loss

✓

Deep chronic infiltrate

✓

Intestinal metaplasia

✓

ECL hyperplasia

Slide 64 · Key clinicopathologic causal chain

CD4⁺ T cells and anti-parietal cell immunity → oxyntic gland injury.

Parietal-cell loss → achlorhydria → hypergastrinemia → ECL proliferation.

Intrinsic factor loss → vitamin B₁₂ deficiency → pernicious anemia / neurologic risk.

Atrophy plus metaplasia → increased gastric adenocarcinoma risk.

Autoimmune oxyntic

Parietal-cell loss

Acid production ↓

Gastrin ↑ → ECL hyperplasia

Intrinsic factor ↓

Vitamin B₁₂ deficiency → anemia

Two distinct consequences — schematic

Slide 65 · Primary reference and source boundaries

Robbins, Cotran & Kumar: Pathologic Basis of Disease, 11th ed. (2026).

Chapter 17: The Gastrointestinal Tract—autoimmune atrophic gastritis.

Adjacent source context: stomach anatomy, H. pylori gastritis, and mucosal metaplasia.

Morphology diagrams are original schematics, not tissue photomicrographs.