Stress Related Mucosal Disease

Slide 1 · Stress-Related

Mucosal Disease

Etiology • Mechanisms • Morphology • Clinicopathologic correlation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

After this lecture, distinguish:

Clinical settings and pathogenesis of stress-related gastric mucosal injury

Stress, Curling, and Cushing ulcer patterns

Acute stress-ulcer morphology versus chronic peptic ulcer morphology

Clinical consequences and alternative causes of gastric bleeding

Slide 3 · Definition: Severe physiologic stress causes mucosal injury

Acute injury of the gastric mucosa associated with critical physiologic illness or trauma.

Injury spans shallow erosions to ulceration.

The major mechanistic theme is impaired local perfusion.

Slide 4 · Physiologic stress is not everyday “stress”

Severe physiologic stress

Shock, sepsis, severe trauma

Extensive burns or intracranial disease

Major surgery or serious illness

Broader peptic-ulcer context

Psychological stress is listed as a PUD risk factor

Distinct from ICU stress-related mucosal disease

Avoid collapsing these entities into one

Slide 5 · Settings linked to stress-related mucosal disease

Circulatory insults

Shock and sepsis can compromise gastric mucosal blood flow.

Tissue injury

Severe trauma and extensive burns create physiologic stress.

Neurologic illness

Intracranial disease has a distinctive acid-related mechanism.

Serious illness

Major surgery and other severe medical diseases are associated.

Slide 6 · Shock: A perfusion-centered pathway

Shock

Systemic hypotension

Reduced gastric mucosal flow

Acute mucosal injury

Local ischemia is the central link between hemodynamic compromise and tissue damage.

Slide 7 · Sepsis: When mucosal blood flow is compromised

Sepsis

Severe physiologic stress

Reduced local perfusion

Mucosal injury

Sepsis among the common settings for stress ulcers.

Slide 8 · Severe trauma is a major setting

Key interpretive points:

Severe trauma is associated with stress ulcers.

Perfusion failure may accompany severe physiologic stress.

Assess the injury in relation to the systemic clinical condition.

Slide 9 · Severe burns: The Curling-ulcer association

Severe burns or trauma can be accompanied by ulcers in the stomach and proximal duodenum.

These lesions are termed Curling ulcers.

The eponym carries both an anatomic and clinical association.

Slide 10 · Intracranial disease: A distinct pathway

Intracranial disease

Vagal nuclei stimulation

Gastric acid hypersecretion

Ulceration

Cushing ulcers are associated with intracranial disease; They also have greater perforation risk.

Slide 11 · Major surgery and serious medical disease

Clinical context:

Stress-related mucosal disease can follow major surgical procedures.

Serious medical disease is an additional recognized setting.

The common denominator is physiologic severity rather than a single diagnosis.

Slide 12 · Different stressors, overlapping pathways

Shock / sepsis

Perfusion-related gastric injury is central.

Burns / trauma

Severe injury accompanies stress-ulcer formation.

Intracranial disease

Vagal stimulation and increased acid have a distinct role.

Slide 13 · Gastric defense is a layered system

Mucus + phospholipids

Bicarbonate-rich surface layer

Epithelial barrier

Mucosal perfusion

These defenses collectively protect tissue despite highly acidic gastric contents.

Slide 14 · Mucus limits direct epithelial exposure

Foveolar-cell secretions form a mucus–phospholipid layer over the gastric mucosa.

Prevents food particles from contacting the epithelium directly.

Helps maintain a protected surface fluid compartment.

Slide 15 · Bicarbonate creates a protective microenvironment

Gastric acid in lumen

Surface mucus layer

Bicarbonate secretion

Near-neutral epithelial surface

The protective pH gradient matters when acid approaches underlying tissue.

Slide 16 · Surface epithelium: A physical barrier

The gastric epithelial sheet:

Limits back diffusion of gastric acid.

Prevents excessive movement of luminal material into the lamina propria.

Protects the mucosa from luminal digestive enzymes.

Slide 17 · Mucosal vasculature maintains tissue integrity

Mucosal blood flow

Oxygen + nutrient delivery

Removal of back-diffused acid

Support of mucosal defense

Perfusion protects the mucosa chemically and metabolically.

Slide 18 · Epithelial renewal contributes to protection

Dynamic tissue maintenance:

Surface foveolar cells are replaced over approximately 3–7 days.

The barrier depends on ongoing epithelial replacement.

Acute tissue injury and subsequent re-epithelialization are related processes.

Slide 19 · Mucosal injury reflects a balance

Protective factors

Mucus, phospholipids, bicarbonate

Intact epithelial barrier

Adequate blood supply and renewal

Damaging influences

Luminal acid and enzymes

Ischemia or reduced oxygen delivery

Failure of local protective mechanisms

Slide 20 · Local ischemia is the dominant mechanism

Stress-related gastric mucosal injury is most often related to local ischemia.

Systemic hypotension can limit gastric oxygen delivery.

Stress-induced splanchnic vasoconstriction reduces local flow.

Slide 21 · Systemic hypotension is one route to ischemia

Hypotension

Reduced gastric perfusion

Ischemic mucosal stress

Erosion or ulcer

The stomach is vulnerable when its normally rich mucosal blood supply falls.

Slide 22 · Splanchnic vasoconstriction is another route

Severe stress

Splanchnic vasoconstriction

Reduced gastric blood flow

Mucosal ischemia

Splanchnic vascular narrowing can compromise perfusion even when acid is not the primary initiating event.

Slide 23 · Endothelin-1 may intensify perfusion injury

Increased endothelin-1 release

Vasoconstriction

Local gastric ischemia

Mucosal damage

Upregulation and release of endothelin-1 as a contributor.

Slide 24 · Ischemia undermines multiple defenses

The microcirculation is not merely a nutrient supply.

It delivers oxygen and supports epithelial metabolism.

It washes out gastric acid that has diffused into the lamina propria.

Slide 25 · Systemic acidosis can amplify injury

Systemic acidosis

Reduced pH gradient

Impaired acid washout

More tissue injury

This as an additional contributing mechanism.

Slide 26 · What is the pH-gradient hypothesis?

An acid washout mechanism:

A pH gradient favors clearance of acid that back-diffuses into lamina propria.

Systemic acidosis reduces this gradient.

Consequently, local mucosal injury may be aggravated.

Slide 27 · Intracranial injury changes the acid balance

Intracranial injury

Direct vagal nuclei stimulation

Increased gastric acid output

Ulcer formation

This neurogenic pathway is described as the proposed basis of Cushing ulcers.

Slide 28 · Two mechanistic emphases

Most stress-related injury

Local ischemia

Systemic hypotension or vasoconstriction

Endothelin-1 and acidosis may contribute

Cushing-associated injury

Intracranial disease

Vagal nuclei stimulation

Gastric acid hypersecretion

Slide 29 · Integrated model: Stress ulcers have multiple inputs

Severe physiologic stress

Perfusion loss ± systemic acidosis

Mucosal defense failure

Acute erosions / ulcers

Intracranial injury adds a distinctive acid-hypersecretion pathway.

Slide 30 · Three clinically named ulcer patterns

Stress ulcers

Common with shock, sepsis, or severe trauma.

Curling ulcers

Stomach and proximal duodenum; Severe burns or trauma.

Cushing ulcers

Gastric, duodenal, or esophageal; Intracranial disease.

Slide 31 · Stress ulcers: The general critical-illness pattern

Shock, sepsis, and severe trauma are common clinical settings.

Acute mucosal injury may be multifocal.

Profound systemic illness is the essential clinical clue.

Slide 32 · Curling ulcers: Location plus severe injury

The eponym refers to ulcers in the proximal duodenum and stomach.

Observed in severe burns or trauma.

Anatomic location alone does not establish the clinical association.

Slide 33 · Cushing ulcers: Intracranial pathology

Cushing ulcers may involve stomach, duodenum, and esophagus.

Occur in the setting of intracranial disease.

Compared with other stress ulcers, perforation risk is greater.

Slide 34 · Names, contexts, and anatomic sites

Term

Clinical context

Typical sites

Stress ulcer

Shock; Sepsis; Severe trauma

Often gastric

Curling ulcer

Severe burns or trauma

Stomach; Proximal duodenum

Cushing ulcer

Intracranial disease

Stomach; Duodenum; Esophagus

Slide 35 · Injury spans erosions and mucosal ulceration

Stress-related lesions range from shallow erosions to ulcers penetrating the mucosa.

The lesions are benign description.

Extent and depth vary with injury severity.

Slide 36 · Morphologic spectrum: Erosion to ulcer

Shallow erosion

Surface epithelium

Mucosa

Submucosa

Superficial epithelial loss

Ulcer penetrating mucosa

Surface epithelium

Mucosa

Submucosa

Defect extends into the mucosa

Slide 37 · Gross morphology: Usually small, rounded lesions

Acute stress ulcers are typically round and under 1 cm in diameter.

The gastric surface may contain multiple discrete defects.

Size and shape are descriptive—not an independent definitive diagnosis.

Slide 38 · Spatial pattern is an important diagnostic clue

Acute stress ulcers

Chronic peptic ulcer disease

Fundus

Body

Antrum

Often multiple, across the stomach

Fundus

Body

Antrum

Commonly solitary; Gastric antral tendency

Slide 39 · Brown–black ulcer bases reflect altered blood

Acid digestion of extravasated blood can stain an ulcer base brown to black.

This color has a mechanistic explanation.

The appearance should be interpreted in its clinical context.

Slide 40 · From vascular compromise to dark ulcer base

Mucosal damage

Blood extravasation

Acid digestion of blood

Brown–black surface

The ulcer color relates to blood exposed to the acidic gastric environment.

Slide 41 · Microscopy: Sharply defined acute defects

The stress-ulcer boundary is sharply demarcated.

Adjacent mucosa may remain relatively normal.

This spatial pattern contrasts with the chronicity of conventional peptic ulcer disease.

Slide 42 · Adjacent mucosa can appear relatively normal

A distinction worth reporting:

Acute stress ulcers can have an abrupt transition to surrounding mucosa.

Morphology must be integrated with the critical-illness setting.

Chronically scarred background tissue is not the characteristic pattern.

Slide 43 · Stress ulcer versus chronic peptic ulcer: Healing signature

Acute stress ulcer

Sharp demarcation

Relative preservation of adjacent mucosa

Chronic scarring and thickened vessels absent

Chronic peptic ulcer

Usually solitary and chronic

Granulation tissue and fibrous scar

Often thickened larger vessels

Slide 44 · Serositis may accompany an acute stress ulcer

Serosal inflammation is possible in stress-related ulceration.

It is not present in every lesion.

The condition can be more than a surface-only abnormality.

Slide 45 · Absence of fibrosis helps indicate acute injury

Conspicuous scarring is not typical of acute stress ulcers.

Scarring is a hallmark of chronic peptic ulcers.

Histologic chronicity should not be inferred solely from ulcer depth.

Slide 46 · Absence of thickened vessels is another clue

Chronic peptic-ulcer-type vascular wall thickening is conspicuously absent.

Chronic peptic ulcers can contain thickened larger vessels within scar.

The distinction reflects the duration and tissue response.

Slide 47 · Morphologic distinctions: Acute stress vs chronic peptic

Feature

Acute stress ulcer

Chronic peptic ulcer

Number

Often multiple

Usually solitary

Distribution

Across the stomach

Often antrum / proximal duodenum

Edge

Sharp demarcation

Punched-out defect

Background

Relatively normal adjacent mucosa

Frequently chronic gastritis

Chronic scar

Absent

Characteristic

Thickened vessels

Absent

Can occur in ulcer base

Slide 48 · Healing can restore the surface epithelium

Acute mucosal injury

Shallow erosions or ulcers

Underlying cause controlled

Perfusion and injury conditions improve

Surface restored

Complete re-epithelialization in days–weeks

Recovery follows treatment of the stressor; Prophylaxis alone does not eliminate the cause.

Slide 49 · Microscopic mucosal damage is common in critical illness

Most intensive-care patients have histologic evidence of gastric mucosal damage.

Histologic injury does not equate to major hemorrhage.

The severe bleeding subgroup is much smaller.

Slide 50 · Clinically important bleeding is substantially less common

That 1%–4% of intensive-care patients require transfusion.

This is a textbook figure for clinically consequential bleeding.

It should not be mistaken for the prevalence of any microscopic injury.

Slide 51 · Frequency and severity are different measures

Histologic involvement

Common in critical illness

Can be detected without overt bleeding

Represents mucosal injury

Clinically important bleeding

Much less frequent

Transfusion required in 1%–4%

Represents a clinical consequence

Slide 52 · Perforation is an uncommon complication

Perforation and other complications are rarer than bleeding.

Cushing ulcers carry relatively greater perforation risk.

Relative risk does not mean that perforation is common.

Slide 53 · Clinical strategy addresses mechanism and context

Recognize critical illness

Limit acid-mediated damage

Correct the systemic stressor

Permit mucosal healing

Correction of the underlying condition as most effective.

Slide 54 · Acid suppression is used prophylactically

Proton pump inhibitors are frequently used to blunt stress ulceration.

This is a statement of textbook practice, not a patient-specific prescribing guideline.

Risk and necessity are determined clinically.

Slide 55 · Treating the underlying condition is central

Correction of the precipitating severe illness is the most effective approach.

An ischemic mechanism cannot be corrected by acid suppression alone.

As physiologic injury resolves, complete re-epithelialization may follow.

Slide 56 · Not every acute gastric bleed is a stress ulcer

Dieulafoy lesion

Abnormal submucosal arteriole erodes through surface epithelium.

GAVE

Ectatic antral vessels produce patterned mucosal erythema.

Coagulopathy

Systemic bleeding disorders can mimic stress lesions.

Slide 57 · Dieulafoy lesion: A focal arterial cause

Abnormal submucosal arteriole

Focal epithelial erosion

Arterial bleeding

Recurrent gastric hemorrhage

Typically near the lesser curvature by the gastroesophageal junction.

Slide 58 · Dieulafoy bleeding can be disproportionately large

Important features:

Usually located near the gastroesophageal junction on the lesser curvature.

Bleeding may be recurrent and copious despite a small mucosal defect.

Nonsteroidal anti-inflammatory drugs may increase bleeding risk.

Slide 59 · GAVE: Longitudinal erythematous stripes

Gastric antral vascular ectasia produces alternating red and pale mucosal stripes.

Endoscopic pattern is called “watermelon stomach.”

Red stripes reflect ectatic mucosal vessels.

Slide 60 · GAVE histology identifies the vascular substrate

Reactive gastropathy with dilated capillaries containing fibrin thrombi.

Vascular ectasia explains the endoscopic erythema.

The antral localization is an important anatomic clue.

Slide 61 · GAVE has clinical associations beyond acute stress

The Robbins description notes:

GAVE is most often idiopathic.

It may be associated with cirrhosis or systemic sclerosis.

Recurrent bleeding can lead to occult blood and iron deficiency anemia.

Slide 62 · A systemic coagulopathy can mimic stress ulceration

Coagulopathy may produce gastric lesions resembling stress ulcers.

The bleeding mechanism may be systemic rather than limited to local ulcer biology.

Clinical context is necessary for interpretation.

Slide 63 · Upper GI bleeding: Differentiating clues

Condition

Clue

Pathologic mechanism

Stress ulcers

Severe physiologic stress; Often multiple

Ischemic mucosal injury

Dieulafoy lesion

Focal lesion near lesser curvature / GEJ

Abnormal submucosal arteriole

GAVE

Striped antral erythema; Chronic blood loss

Ectatic mucosal capillaries

Coagulopathy

Systemic hemostatic disturbance

Bleeding with ulcer-like damage

Slide 64 · Case: Shock and multiple small gastric lesions

A critically ill patient in shock has several small, sharply delimited gastric ulcers with dark bases.

Interpretation

Which hemodynamic process best explains the injury?

Which gross findings favor acute stress ulceration?

Slide 65 · Case resolution: Perfusion failure with acute morphology

Shock → systemic hypotension → gastric mucosal ischemia.

Multiple discrete ulcers and dark bases support acute stress injury.

Dark coloration is consistent with acid-altered extravasated blood.

Slide 66 · Case: Intracranial disease and ulceration

A patient with intracranial disease develops gastric and duodenal ulceration.

Interpretation

Name the eponym and the proposed neurogenic mechanism.

Which major complication has relatively greater risk?

Slide 67 · Case resolution: Cushing ulcers

Intracranial injury can stimulate vagal nuclei and increase gastric acid secretion.

The corresponding ulcers are termed Cushing ulcers.

They have an increased risk of perforation.

Slide 68 · Case: Severe burns and proximal duodenal ulcers

Following extensive burns, a patient develops ulcers in the stomach and proximal duodenum.

Interpretation

Which eponym is supported by the setting and sites?

Why is the injury categorized as stress-related?

Slide 69 · Case resolution: Curling ulcers

Burn-associated lesions in the stomach and proximal duodenum are Curling ulcers.

The patient has severe physiologic stress rather than an isolated acid disorder.

Clinical association is essential for the eponym.

Slide 70 · Case: Antral stripes and chronic blood loss

Endoscopy shows alternating erythematous and pale longitudinal stripes in the antrum; The patient has iron deficiency anemia.

Interpretation

Which vascular lesion is most consistent with this pattern?

What are its characteristic microscopic findings?

Slide 71 · Case resolution: Gastric antral vascular ectasia

GAVE produces the “watermelon stomach” pattern.

Ectatic mucosal vessels with fibrin-containing thrombi are characteristic.

Recurrent bleeding can cause iron deficiency anemia.

Slide 72 · Final synthesis: Mechanism predicts morphology

The reasoning sequence:

Severe physiologic stress is linked predominantly to local ischemia.

Acute multifocal erosions and ulcers differ from scarred chronic peptic ulcers.

Bleeding can be clinically important; Perforation is less common.

Recovery depends fundamentally on correction of the precipitating condition.

Slide 73 · Rapid review: Recognize the pattern

Observation

Interpretation

Shock with multiple small ulcers

Acute stress-related mucosal disease

Major burns + proximal duodenal ulcer

Curling ulcer

Intracranial disease + ulcers

Cushing ulcer

Antral longitudinal red stripes

Gastric antral vascular ectasia

Focal lesser-curvature arterial bleeding

Dieulafoy lesion

Slide 74 · Primary textbook reference

Robbins, Cotran & Kumar

Pathologic Basis of Disease

11th edition (2026)

Chapter 17 — The Gastrointestinal Tract

Stress-Related Mucosal Disease; related stomach and peptic ulcer sections