Peptic Ulcer Disease

Slide 1 · Peptic Ulcer Disease

Pathogenesis · Morphology · Clinical consequences

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Explain why host defenses fail in chronic peptic ulceration

Trace the effects of H. Pylori, NSAIDs, and impaired perfusion

Recognize typical gross and microscopic ulcer morphology

Relate morphology to hemorrhage, perforation, and obstruction

Clinical and morphologic integration

Slide 3 · Peptic ulcer disease: A defined lesion

Chronic ulceration predominantly affects the stomach or proximal duodenum.

An ulcer is a tissue defect associated with sustained acid-peptic injury.

H. Pylori infection, NSAIDs, and smoking dominate the etiologic context.

The usual setting is pre-existing chronic gastritis.

Chronic ulcer ≠ any superficial erosion

Slide 4 · Two principal sites, one shared mechanism

Proximal duodenum

Duodenal disease usually involves the first few centimeters beyond the pylorus.

Distal stomach

Gastric disease commonly involves the lesser curvature at the body–antrum junction.

Location reflects acid load and mucosal vulnerability

Slide 5 · Regional physiology explains ulcer geography

Antrum → gastrin

Antral G cells stimulate gastrin release and downstream acid secretion.

Body/fundus → acid

Body and fundus parietal cells secrete gastric acid.

Slide 6 · Gastric defense is an integrated system

Healthy epithelium resists exposure to acid and peptic enzymes.

Mucus, bicarbonate, epithelial integrity, prostaglandins, and blood flow act together.

Luminal barrier

Cellular barrier

Blood flow / repair

Loss of several protective functions amplifies injury

Slide 7 · Mucus creates a protected surface microenvironment

Foveolar secretions generate a mucus–phospholipid coating.

The mucus layer limits direct luminal contact with epithelial cells.

Within the unstirred fluid layer, bicarbonate maintains near-neutral surface pH.

The surface pH is not the same as luminal pH

Slide 8 · Bicarbonate prevents acid damage at the epithelium

Surface cells secrete bicarbonate into the overlying mucus.

Local neutralization reduces acid exposure adjacent to cell membranes.

Bicarbonate secretion

Neutral surface microclimate

Reduced epithelial injury

Slide 9 · Epithelial integrity limits back-diffusion

An intact epithelial barrier restricts movement of luminal acid and enzymes.

Compromised barrier permits damaging material to reach the lamina propria.

Foveolar cells renew rapidly, supporting surface restitution.

Slide 10 · Perfusion sustains repair and acid clearance

The mucosal vasculature supplies oxygen and nutrients.

It also removes acid that penetrates the epithelial barrier.

Ischemia creates vulnerability even without an increase in acid output.

Mucosal blood flow

Oxygen + nutrient delivery

Epithelial survival / repair

Slide 11 · Prostaglandins coordinate multiple defenses

PGE₂ and PGI₂ promote mucus, bicarbonate, and phospholipid secretion.

They support mucosal blood flow and epithelial restitution.

They also restrain acid secretion.

Prostaglandin production

Barrier + perfusion + repair

Mucosal protection

Slide 12 · Ulceration is a failure of balance

Damaging forces: Gastric acid and peptic enzymes.

Protection: Mucus, bicarbonate, intact epithelium, blood flow, repair.

Ulcers form when chronic injury overwhelms these defenses.

DAMAGING FORCESacid · pepsin

DEFENSIVE FORCESbarrier · blood flow · repair

ULCER if injury exceeds protection

Acid is necessary context; Impaired defense is equally important

Slide 13 · Chronic gastritis provides the tissue background

PUD generally evolves in chronically inflamed gastroduodenal mucosa.

Not every patient with gastritis develops a peptic ulcer.

Chronic gastritis

Altered acid / defense balance

Chronic ulcer

Slide 14 · Three dominant etiologic pathways

H. Pylori

Antral inflammation, increased acid and lower duodenal bicarbonate

NSAIDs

COX inhibition and loss of protective prostaglandins

Smoking

Reduced blood flow, oxygenation, and healing

Slide 15 · H. Pylori is adapted to the mucus niche

The organism resides in surface mucus close to foveolar cells.

Flagella permit movement within mucus and away from acidic niches.

Adhesins mediate attachment to epithelial surfaces.

Flagella

Mucus colonization

Adhesion

Slide 16 · Urease supports bacterial persistence

H. Pylori urease converts endogenous urea to ammonia.

Ammonia buffers acidity near the organism.

Persistence supports long-term gastritis and its complications.

Urea

Urease → ammonia

Higher local pH

Slide 17 · Bacterial products modify the inflammatory response

CagA and VacA are among studied H. Pylori virulence factors.

CagA can alter epithelial signaling and structural organization.

Pathogenic outcome reflects bacterial traits interacting with host factors.

Direct causality for specific clinical outcomes remains difficult to prove.

Slide 18 · Antral-predominant gastritis alters gastrin physiology

Antral inflammation enhances gastrin production.

Parietal-cell expansion in the gastric body increases acid output.

This secretory phenotype increases peptic-ulcer susceptibility.

Antral H. Pylori gastritis

↑ Gastrin / parietal stimulation

↑ Gastric acid

Slide 19 · Duodenal bicarbonate is also reduced

The common H. Pylori-associated PUD phenotype includes reduced duodenal bicarbonate secretion.

Increased acid delivery and weaker neutralization act in the same direction.

Increased acid burden

Reduced bicarbonate

Duodenal mucosal injury

Slide 20 · Acid hypersecretion favors duodenal ulceration

Antral phenotype

Antral-predominant H. Pylori gastritis commonly retains or increases acid secretion.

Duodenal ulcer risk

The proximal duodenum is vulnerable to excessive acid-peptic load.

Slide 21 · Atrophic gastritis shifts the acid phenotype

Acid-preserved gastritis

Loss of parietal cells in body/fundus lowers acid secretion.

Atrophic, hypoacid gastritis

Gastric mucosal atrophy is associated with lower antral/duodenal ulcer risk.

Slide 22 · One infection can lead to divergent outcomes

Antral-predominant disease may be associated with increased acid output and ulceration.

Extensive atrophy may instead lower acid production and associate with intestinal metaplasia.

Antral inflammation → ulcer

Body/fundus atrophy → metaplasia

Schematic branches / outcomes

Pattern of gastritis matters more than infection status alone

Slide 23 · Why does only a subset develop ulcers?

H. Pylori infection is common, but clinical PUD is not inevitable.

Host inflammatory and defense responses vary.

Bacterial pathogenicity also varies among isolates.

The precise transition from gastritis to PUD as incompletely understood.

Slide 24 · NSAIDs reduce the prostaglandin defense network

COX inhibition reduces synthesis of PGE₂ and PGI₂.

Mucus, bicarbonate, perfusion, and repair are compromised.

Acid-mediated injury becomes more likely at the same luminal acid exposure.

NSAID exposure

↓ COX-derived prostaglandins

Weakened defense → injury

Slide 25 · COX-1 predominates, but COX-2 also contributes

COX-1 contribution

Nonselective NSAIDs generally have substantial gastrointestinal toxicity.

COX-2 contribution

Selective COX-2 inhibition does not eliminate mucosal injury risk.

Slide 26 · Several drug exposures amplify ulcer risk

NSAIDs

Directly impair protective prostaglandin synthesis

Corticosteroids + NSAIDs

Potentiation listed Table 17.3

Low-dose aspirin + H. Pylori

Increased gastric injury with concurrent infection

Slide 27 · H. Pylori and aspirin are clinically synergistic

The combination increases gastric injury risk beyond either isolated exposure.

Medication history and infection status both matter.

H. Pylori gastritis

Aspirin exposure

Amplified gastric injury

Slide 28 · Smoking impairs tissue-level resilience

Smoking is an established clinical association with PUD.

Reduced mucosal perfusion and oxygenation impair the capacity to heal.

Synergy with H. Pylori for gastric ulcers.

Cigarette use

↓ Blood flow / oxygenation

Delayed mucosal repair

Slide 29 · Perfusion-limiting exposures increase vulnerability

Cardiovascular disease

Reduced oxygenation / mucosal blood flow (proposed mechanism)

Cocaine use

Vasoconstrictive reduction in mucosal blood flow

Chronic obstructive pulmonary disease

Listed associated risk condition

Slide 30 · Hypersecretory states broaden ulcer distribution

Zollinger–Ellison syndrome causes excessive gastric acid production.

Ulcers can involve the stomach, duodenum, or jejunum.

Atypical distribution warrants attention to hypersecretory causes.

Endocrine hypersecretion

Excess acid

Distal / multiple-site injury

Slide 31 · Ectopic gastric mucosa can injure adjacent bowel

Duodenal gastric heterotopia

Local acid secretion and peptic injury

Meckel diverticulum

Ileal ulceration near ectopic gastric mucosa

Esophageal inlet patch

Local acid-peptic injury

Slide 32 · Less common etiologic associations

Alcoholic cirrhosis

Primarily duodenal PUD association

Psychological stress

May increase gastric acid secretion

Endocrine-cell hyperplasia

Parietal-cell growth / increased acid output

CMV or HSV

Uncommon infection-related ulcer disease

Slide 33 · Risk-factor assessment should be causal

More injurious exposure

High acid burden: Gastrin stimulation, Zollinger–Ellison syndrome, ectopic acid secretion.

Less effective protection

Weak mucosal defense: NSAIDs, smoking, compromised perfusion, chronic inflammation.

Slide 34 · Changing epidemiology reflects changing exposures

Falling H. Pylori prevalence

H. Pylori-related disease has declined as infection prevalence decreases.

Increasing NSAID exposure in older age

Older adults have increasing NSAID-associated ulcer disease account.

Slide 35 · Proximal duodenum is the dominant site

Typical chronic duodenal peptic ulcers lie only a short distance beyond the pyloric valve.

The location is consistent with excessive gastric acid delivery.

Gastric body

Antrum / pylorus

Proximal duodenum

Slide 36 · Gastric ulcers favor the lesser curvature

Most common location: Lesser curvature near the body–antrum interface.

The distribution differs from the proximal duodenal predilection.

Gastric body

Antrum / pylorus

Proximal duodenum

Slide 37 · Gross ulcer shape is diagnostically informative

Chronic peptic ulcers are round or oval.

The defect is sharply punched out and well demarcated.

The floor is often smooth and clean.

Schematic en-face ulcer crater

Slide 38 · The typical ulcer margin is not heaped up

Peptic configuration

Peptic ulcer: Margin usually flush with surrounding mucosa; May overhang.

Concerning neoplastic configuration

Neoplastic ulcer: Heaped-up, irregular margins raise concern for carcinoma.

Slide 39 · Margin appearance helps—not proves—etiology

A clean punched-out crater suggests a benign peptic pattern.

Heaped-up margins are more characteristic of cancer.

Morphology is not a substitute for appropriate lesion evaluation.

Ulcer appearance alone cannot categorically exclude malignancy.

Slide 40 · Why is the ulcer base often clean?

Acid and peptic enzymes digest surface exudate.

As debris is removed, the base appears smooth and relatively clean.

Active inflammation and granulation tissue persist beneath the surface.

Peptic digestion of exudate

Clean-appearing crater

Underlying tissue injury

Slide 41 · Chronic peptic ulcers have layered histology

Superficial fibrinoid or necroinflammatory material.

Predominantly neutrophilic active inflammation.

Granulation tissue with immature vessels.

Deep collagenous scar and remodeled vessels.

Surface exudate

Neutrophils

Granulation tissue

Fibrosis

Schematic cross-sectional strata, not a tissue image

Slide 42 · Surface exudate records active tissue injury

A thin fibrinoid layer may cover an active ulcer.

Fibrinoid debris reflects injury at the exposed ulcer surface.

This zone should be distinguished from the deeper healing response.

Slide 43 · Neutrophils indicate ongoing active inflammation

Neutrophils predominate in the active superficial inflammatory zone.

The infiltrate occurs above deeper chronic repair tissue.

Active injury and repair can coexist in one chronic lesion.

Slide 44 · Granulation tissue provides the reparative bed

New vessels emerge within an inflammatory stromal matrix.

Neutrophils and mononuclear leukocytes can be present.

Granulation tissue sits beneath the active surface zone.

Immature vascular channels

Inflammatory cells

Reparative stroma

Slide 45 · Chronic ulcers create a collagenous scar

A deeper collagenous layer lies beneath granulation tissue.

The fibrotic reaction can involve the full thickness of the wall.

Scar contraction distorts local wall architecture.

Ulcer surface

Repairing zone

Fibrous scar

Deep gastric wall

Schematic cross-sectional strata, not a tissue image

Slide 46 · Remodeled vessels explain severe hemorrhage

Larger vessels within the ulcer scar often have thickened walls.

Some are thrombosed, while erosion of others can cause life-threatening bleeding.

Scarred ulcer base

Thickened / eroded vessel

Hemorrhage

Slide 47 · Radiating mucosal folds reflect contraction

Deep fibrosis pulls adjacent mucosa toward the crater.

Mucosal folds may radiate outward from the ulcer.

The fold pattern is a morphologic consequence of chronic scarring.

Schematic en-face ulcer crater

Slide 48 · Duodenal foveolar metaplasia may be protective

Gastric-type mucin cells can appear in chronically damaged duodenal mucosa.

Gastric-type epithelium tolerates acid better than native intestinal epithelium.

This as a possible protective response.

Chronic acid exposure

Gastric-type metaplasia

Improved acid tolerance?

Slide 49 · Most peptic ulcers occur singly

>80%

Solitary ulcer

More than 80% of patients have a solitary peptic ulcer.

Multiplicity is possible and may alter etiologic reasoning.

Slide 50 · An erosion is not equivalent to chronic PUD

Superficial erosion

Erosion: Superficial mucosal tissue loss, often accompanying acute injury.

Chronic deep ulcer

Chronic ulcer: A deeper defect with granulation and fibrous scarring.

Slide 51 · Deep injury creates bleeding and perforation risk

Expansion into scarred vessels produces clinically important hemorrhage.

Full-thickness tissue destruction can breach the wall and cause perforation.

Vessel involvement → bleeding

Transmural loss → perforation

Schematic branches / outcomes

Slide 52 · Bleeding is the most frequent major complication

15–20%

Bleeding

Bleeding develops in 15%–20% of affected patients Table 17.4.

It may be the initial presentation and may be life threatening.

Slide 53 · Gastrointestinal blood loss has two clinical faces

Visible hemorrhage

Overt hemorrhage: A presentation requiring urgent clinical recognition.

Iron deficiency anemia

Chronic or occult blood loss: Can manifest as iron deficiency anemia.

Slide 54 · Why does a benign ulcer sometimes bleed massively?

A chronic crater reaches and injures larger arteries or veins.

The altered vessel lies within inflamed fibrotic tissue.

Loss of vessel integrity allows major luminal hemorrhage.

Deep ulceration

Vessel-wall injury

Acute hemorrhage

Slide 55 · Perforation crosses the entire wall

Deep ulceration may extend through all wall layers.

Peritoneal contamination produces a surgical emergency.

The lesion is no longer confined to the mucosa and submucosa.

Mucosa

Submucosa

Muscular wall

Peritoneal breach

Schematic cross-sectional strata, not a tissue image

Slide 56 · Free subdiaphragmatic air is an imaging clue

Perforation can release luminal gas into the peritoneal cavity.

Upright abdominal radiography may reveal air beneath the diaphragm.

This is an interpretive sign of possible hollow-viscus perforation.

Wall perforation

Free intraperitoneal gas

Subdiaphragmatic air

Slide 57 · Penetrating ulcers may cause referred pain

Localized epigastric pain

Usual pain: Epigastric burning or aching.

Pain outside epigastrium

Penetrating ulcer pain may be perceived in the back, left upper quadrant, or chest.

Slide 58 · Scar and edema can obstruct gastric emptying

Chronic ulcer healing produces edema and fibrotic contraction.

Narrowing is most associated with pyloric-channel ulcers.

Duodenal ulceration can also produce obstruction.

Recurrent injury / edema

Fibrotic narrowing

Outlet obstruction

Slide 59 · Obstruction has a characteristic symptom pattern

Crampy, incapacitating abdominal pain may develop.

Vomiting can be substantial with severe narrowing.

Total obstruction with intractable vomiting is uncommon.

Slide 60 · Major PUD complications in one view

Bleeding

15%–20%; Most frequent; May be first presentation

Perforation

Up to 5%; Serious acute complication

Obstruction

About 2%; Usually chronic edema or scar

Slide 61 · Ulcer-related mortality is complication-weighted

Bleeding ~25% of ulcer deaths

Bleeding accounts for about 25% of ulcer-related deaths Table 17.4.

Perforation ~⅔ of ulcer deaths

Perforation accounts for about two-thirds of ulcer-related deaths in that table.

These are shares of ulcer-related deaths—not patient mortality rates

Slide 62 · Typical ulcer pain is epigastric and burning

The classic symptom is burning or aching in the epigastrium.

Pain may fluctuate over the day and recur.

Clinical assessment must also consider hemorrhage or perforation.

Slide 63 · Meal-related timing is a useful historical clue

Pain commonly appearing 1–3 hours after meals.

Pain may improve after food or alkali.

This is a typical pattern, not a diagnostic requirement.

Meal

1–3 h later: Pain

Food / alkali: Relief

Slide 64 · Nocturnal pain occurs pattern

Symptoms can worsen at night.

Frequent pain around 11 p.m.–2 a.m.

Clinical presentations are not uniform and timing does not localize every ulcer.

Slide 65 · Not all patients present with pain

Dyspeptic symptoms

Some patients report nausea, vomiting, bloating, or belching.

Complication-driven presentation

Others first present with anemia, hemorrhage, or perforation.

Slide 66 · Weight loss requires interpretation in context

Significant weight loss is included among reported PUD manifestations.

Symptoms alone are insufficient to assign a benign cause.

An atypical ulcer configuration warrants evaluation for an alternative diagnosis.

Slide 67 · H. Pylori is detectable on gastric biopsy

Organisms generally reside in surface mucus over foveolar epithelium.

Routine H&E may show organisms; Special stains or IHC improve recognition.

Antral mucosa is commonly colonized, but distribution can be patchy.

Slide 68 · Noninvasive tests assess H. Pylori infection

Urea breath test

Detects the consequence of bacterial urease activity

Fecal bacterial detection

Noninvasive organism-based testing

Serologic antibodies

Evidence of anti–H. Pylori immune response

Slide 69 · Biopsy-based H. Pylori tests complement histology

Histologic detection

Demonstrates organisms and mucosal inflammation

Rapid urease test

Detects bacterial enzyme activity

Culture or PCR

Can identify organism or bacterial DNA

Slide 70 · Treatment targets infection and luminal acid

H. Pylori eradication addresses a major cause of persistent gastritis.

Proton pump inhibitors suppress gastric acid production.

Combining etiologic treatment with acid suppression supports healing.

Eradicate H. Pylori

Suppress acid with PPI

Allow ulcer healing

Slide 71 · Withdrawal of injurious drugs matters

Remove or reassess NSAID exposure where clinically feasible.

Even selective COX-2 inhibitors can impair mucosal protection.

Persistent exposure can hinder healing despite acid suppression.

Slide 72 · Eradication reduces the recurrence burden

<20%

Recurrence following clearance

Recurrence below 20% after successful H. Pylori clearance.

The figure concerns recurrence following successful eradication—not untreated natural history.

Slide 73 · Chronic PUD differs from stress-related injury

Chronic peptic ulcer

Chronic PUD is linked to sustained gastritis, acid imbalance, granulation, and scarring.

Stress-related mucosal injury

Acute stress-related ulcers often arise with physiologic stress and ischemia and lack the mature chronic scar pattern.

Slide 74 · Case: Recurrent epigastric pain with antral gastritis

HYPOTHETICAL TEACHING VIGNETTE

Hypothetical: A patient has epigastric pain and chronic antral H. Pylori gastritis.

Which physiologic sequence best explains an associated proximal duodenal ulcer?

Identify the changed acid and bicarbonate pathways.

Mechanisms to consider

Antral inflammation

Acid secretion

Duodenal mucosal protection

Slide 75 · Case interpretation: Secretory and defense imbalance

Antral inflammation promotes gastrin and parietal-cell stimulation.

Gastric acid delivery increases while duodenal bicarbonate defense falls.

The proximal duodenum becomes vulnerable to chronic peptic injury.

↑ Gastrin / acid

↓ Duodenal bicarbonate

Proximal duodenal ulcer

Slide 76 · Case: Older adult using NSAIDs with bleeding

HYPOTHETICAL TEACHING VIGNETTE

Hypothetical: An older adult taking NSAIDs develops melena and iron deficiency anemia.

What protective system has been compromised?

What ulcer-base structure explains possible massive hemorrhage?

Mechanisms to consider

NSAID exposure

Chronic crater

Vessel injury

Slide 77 · Case interpretation: Drug effect meets ulcer anatomy

COX inhibition reduces protective prostaglandins.

Ulceration may extend to thickened vessels within fibrous scar.

Vessel injury can produce life-threatening hemorrhage.

↓ Prostaglandin defense

Deep ulcer / scarred vessel

Hemorrhage

Slide 78 · Pathology differential: Peptic versus malignant crater

Typical margin

PUD: Level / possible overhang; Cancer: Often heaped up

Floor

PUD: May be smooth and clean after peptic digestion

Stromal response

Chronic PUD: Granulation and deep fibrous scar

Interpretation

Gross appearance supports but never proves benignity

Slide 79 · Integrated model of chronic peptic injury

Infection or hyperacidity can increase luminal injury.

NSAIDs, smoking, and ischemia can reduce defensive capacity.

Persistent injury causes a crater with acute inflammation, granulation, and scarring.

Increased acid-peptic load

Reduced mucosal defenses

Chronic ulcer → complications

Schematic branches / outcomes

Slide 80 · Five diagnostic anchors

Predilection: Proximal duodenum or gastric lesser curvature

Shape: Solitary, sharply punched-out round/oval crater

Histology: Superficial active injury over granulation and scar

Complications: Bleeding, perforation, obstruction

Etiology: H. Pylori, NSAIDs, cigarette use

Slide 81 · References and image provenance

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. 2026. Ch.17, pp.696–702.

Primary PUD text: pp.701–702; complication frequencies from Table 17.4, p.702.

Robbins Figs. 17.13–17.14: mucosal protection and H. pylori gastritis pathogenesis.

Robbins Fig. 17.17: chronic peptic ulcer morphology; Tables 17.3–17.4: risk factors and complications.