Tissue Necrosis

Slide 1 · Tissue Necrosis

Infection-driven cellular and organ injury

Pathogenesis · morphology · clinicopathologic interpretation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Recognize infection-related tissue necrosis as a dominant histologic reaction pattern.

Explain direct toxin-, microbial-, and host-response–mediated tissue destruction.

Contrast clostridial, diphtheritic, amebic, HSV, and HBV injury.

Interpret necrosis relative to inflammatory infiltrates and preserved tissue architecture.

Slide 3 · Tissue necrosis is a reaction pattern

Necrosis refers to tissue death when substantial numbers of cells are destroyed.

In infection, destruction may be so extensive that it dominates the histologic picture.

It is a tissue-response pattern—not a microbiologic diagnosis by itself.

The nature of the injury and host inflammatory response must be interpreted together.

Slide 4 · Where necrosis fits among infectious patterns

Pattern

Dominant feature

Illustrative setting

Suppurative

Neutrophils; pus

Pyogenic bacterial abscess

Granulomatous

Epithelioid macrophages

Tuberculosis

Cytopathic

Cell injury or proliferation

Herpesvirus lesions

Tissue necrosis

Rapid tissue destruction

Clostridial gas gangrene

Chronic/scarring

Fibrosis after repetitive injury

Chronic viral hepatitis

Slide 5 · Three routes to major tissue damage

1

Microbial exotoxins / enzymes

2

Direct microbial cytopathic injury

3

Host immune injury

Distinct mechanisms can produce overlapping necrosis and inflammation.

Slide 6 · The amount of inflammation is variable

Some fulminant infections show extensive dead tissue with relatively few inflammatory cells.

Other necrotizing infections produce prominent inflammation around injured cells.

Immune suppression changes the reaction: A neutropenic host may have little exudation.

A sparse infiltrate does not exclude a destructive infection.

Slide 7 · Necrosis: The tissue-level sequence

Injury exceeds cellular capacity to recover

Membrane integrity fails and cells die

Cellular contents undergo enzymatic digestion

Tissue architecture is lost or altered

Morphology depends on the relative rates of protein denaturation and tissue digestion.

Schematic sequence

Slide 8 · Microscopic hallmarks of dead cells

Cytoplasm becomes more eosinophilic and often homogeneous on H&E.

Organelles and cellular contents are degraded; Vacuolation may develop.

The plasma membrane and organelle membranes are disrupted.

Cells eventually become ghosts or amorphous debris, depending on tissue digestion.

Slide 9 · Three classic nuclear changes

Pyknosis shrunken, dense nucleus

Karyorrhexis fragmented nucleus

Karyolysis fading / loss of DNA staining

These are recognizable changes in necrotic cells—not organism-specific markers.

Schematic sequence

Slide 10 · Two fundamental necrosis architectures

Finding

Coagulative

Liquefactive

Dead tissue outline

Transiently preserved

Digested and lost

Texture

Relatively firm

Viscous / liquid

Underlying mechanism

Protein/enzyme denaturation

Dominant enzymatic digestion

Typical association

Ischemia outside brain

Infections; CNS hypoxia

Slide 11 · Why infection often causes liquefaction

Microorganisms recruit leukocytes and can release tissue-degrading enzymes.

Enzymes from leukocytes and microbes digest dead cells and extracellular tissue.

Liquefied material may become creamy yellow where leukocytes are abundant.

This common pathway does not imply every necrotic focus contains pus.

Slide 12 · Liquefactive necrosis is not synonymous with pus

Feature

Purulent bacterial abscess

Amebic hepatic lesion

Digested tissue

Present

Present

Neutrophils

Often abundant

May be scant at margins

Typical agent

Pyogenic bacteria

Entamoeba histolytica

Interpretive priority

Recognize neutrophil-rich suppuration

Recognize destructive lesion with few leukocytes

Slide 13 · Low inflammation does not mean low injury

Histologic cell counts can underestimate injury when destruction is rapid.

Toxin-rich or amebic lesions may have extensive necrosis with limited infiltrates.

Neutropenia can additionally suppress the usual suppurative response.

Schematic

Extensive necrosis

Slide 14 · Interpret the tissue reaction in context

Ask: Is tissue architecture preserved, liquefied, ulcerated, or replaced by debris?

Ask: Are neutrophils, lymphocytes, or macrophages predominant—or scarce?

Ask: Does the location suggest muscle, upper-airway, colon, brain, or liver injury?

Do not infer the pathogen solely from one inflammatory pattern.

Slide 15 · Exotoxins can dominate the lesion

Exotoxins are secreted bacterial proteins capable of injuring host cells.

Some are degradative enzymes; Others disrupt intracellular regulatory pathways.

Direct molecular effects can outpace the recruitment of inflammatory cells.

Clostridium perfringens and C. Diphtheriae exemplify severe toxin-linked necrosis.

Slide 16 · Mechanistic distinction among bacterial toxins

Class / example

Primary action

Tissue consequence

Tissue-degrading enzymes

Break down matrix or cell proteins

Invasion; tissue destruction

C. perfringens α-toxin

Membrane phospholipase activity

Myonecrosis; hemolysis

Diphtheria toxin

EF-2 inactivation

Death of affected epithelial cells

Botulinum / tetanus toxins

Block transmitter release

Paralysis, not neuronal necrosis

Slide 17 · Clostridial myonecrosis: Permissive environment

Traumatic or surgical injury creates devitalized tissue

Low-oxygen environment permits anaerobic growth

Organisms release enzymes and α-toxin

Muscle-cell and vascular destruction accelerates

The source emphasizes pre-existing dead tissue as a prerequisite for C. Perfringens growth.

Schematic sequence

Slide 18 · Clostridium perfringens: Relevant biology

An anaerobic, spore-forming gram-positive bacillus.

Along with C. Septicum and others, it causes traumatic or surgical wound myonecrosis.

Necrotic low-oxygen tissue supports bacterial growth.

Toxin production and tissue-degrading enzymes contribute to rapid spread.

Slide 19 · α-Toxin targets cellular membranes

C. Perfringens secretes α-toxin

Phospholipase degrades membrane lecithin

Muscle cells, erythrocytes and platelets are injured

Myonecrosis and hemolysis develop

The same toxin also has sphingomyelinase activity linked to nerve sheath injury.

Schematic sequence

Slide 20 · Why clostridial muscle injury progresses rapidly

Extracellular matrix degradation promotes spread through tissues.

Phospholipid membrane injury destroys muscle cells.

Vascular injury and thrombosis coexist with myonecrosis.

Bacterial fermentation accounts for gas bubbles in tissue.

Schematic

Devitalized muscle

Slide 21 · Clostridial cellulitis versus gas gangrene

Feature

Clostridial cellulitis

Gas gangrene

Distribution

Primarily soft tissue

Prominent skeletal muscle necrosis

Lesion character

Foul-smelling, thin discolored exudate

Edema, bullae, gas, friable muscle

Microscopy

Necrosis out of proportion to neutrophils

Severe myonecrosis, hemolysis, thrombosis

Clinical gravity

Treatable with debridement and antibiotics

Life-threatening process

Slide 22 · Gas gangrene: Gross morphological sequence

Marked edema accompanies acute muscle injury.

Overlying skin may develop large bullae.

Gas bubbles appear within necrotic tissue.

Muscle becomes soft, blue-black and friable.

Schematic

Edema and injury

Bullae + gas

Friable myonecrosis

Gas

Slide 23 · Gas gangrene: What a section may show

Severe myonecrosis is the dominant tissue event.

Extensive hemolysis and vascular damage are described.

Vascular thrombosis accompanies progression.

An extensive exudate may paradoxically contain few inflammatory cells.

Slide 24 · Disproportionate necrosis is a histologic clue

Look for destruction of muscle architecture.

Compare the severity of necrosis with the density of neutrophils.

Sparse inflammation in a rapidly progressing lesion is compatible with clostridial disease.

Schematic

Extensive necrosis

Slide 25 · Clostridial infection: Clinical-pathologic urgency

The textbook calls gas gangrene life-threatening.

Rapidly evolving myonecrosis may follow trauma or surgery.

The tissue effects stem from enzyme activity, membrane damage and vascular injury.

This is a destructive lesion rather than merely a large accumulation of pus.

Slide 26 · Diphtheria: A surface infection with toxin injury

Corynebacterium diphtheriae can proliferate on upper respiratory mucosa.

Toxin causes epithelial necrosis and a fibrinosuppurative reaction.

Bacterial invasion is localized, yet toxin can distribute systemically.

Necrosis and inflammation together produce the pseudomembrane.

Slide 27 · Diphtheria toxin: A precise intracellular lesion

Phage-encoded A–B exotoxin binds and enters cells

A fragment ADP-ribosylates elongation factor 2

EF-2 can no longer support translation

Protein synthesis fails and cells die

Diphtheria necrosis is mechanistically distinct from phospholipase-driven clostridial myonecrosis.

Schematic sequence

Slide 28 · How a pseudomembrane forms

Bacteria attach to respiratory mucosa.

Exotoxin kills surface epithelial cells.

Dense fibrin and inflammatory exudate coagulate over the ulcerated surface.

The gray-black pseudomembrane is not viable tissue.

Schematic

Coagulated fibrin + dead epithelium

Ulcerated mucosal surface

Inflamed, vascularized mucosa

Not a true viable membrane

Slide 29 · The underlying tissue remains inflamed

Necrotic epithelium is associated with a dense fibrinosuppurative exudate.

Underlying tissue contains prominent neutrophils.

Vascular congestion, interstitial edema and fibrin exudation are present.

This illustrates why necrosis can coexist with marked rather than sparse inflammation.

Slide 30 · Why the diphtheritic membrane is dangerous

A tough membrane adheres to ulcerated, vascularized mucosa.

Sloughing may cause bleeding.

Airway compromise or asphyxiation may follow.

The danger is anatomic as well as toxin-mediated.

Slide 31 · Local and distant lesions in diphtheria

Location

Observed injury

Mechanistic significance

Upper airway mucosa

Necrotic epithelium; pseudomembrane

Local toxin action

Myocardium

Fatty change; focal myofiber necrosis

Systemic toxin distribution

Nerves

Polyneuritis; myelin / axonal injury

Systemic toxic effect

Liver / kidney / adrenal

Occasional focal cell necrosis

Remote organ injury

Slide 32 · Two exotoxins, two histologic phenotypes

C. perfringens

C. diphtheriae

Principal vulnerable site

Muscle / soft tissue

Respiratory epithelium

Molecular attack

Membrane phospholipids

Protein translation via EF-2

Dominant structural change

Widespread myonecrosis

Epithelial necrosis and membrane

Inflammatory context

May be cell-poor

Underlying tissue neutrophil-rich

Slide 33 · Amebiasis: Invasive protozoal tissue destruction

Entamoeba histolytica is transmitted by the fecal–oral route.

The organism colonizes the colonic epithelial surface after cyst ingestion.

Trophozoites attach, injure and penetrate mucosa.

Invasion can extend beyond the colon and produce destructive liver abscesses.

Slide 34 · Amebic colonic invasion

Cyst survives stomach passage

Trophozoites colonize colonic surface

Attachment and epithelial apoptosis

Crypt invasion and lateral spread in lamina propria

The invasive geometry helps explain a flask-shaped ulcer.

Schematic sequence

Slide 35 · The flask-shaped amebic ulcer

Surface opening is relatively narrow.

Destruction extends laterally within deeper mucosa.

The resulting broad base under a narrow neck creates the flask profile.

This diagram illustrates described geometry, not a histologic specimen.

Schematic

Narrow neck

Broad deeper spread

Slide 36 · Microscopic recognition has a specific pitfall

Amoebas may resemble macrophages in both size and appearance.

The organism must be considered in the context of the ulcer and tissue destruction.

Morphologic resemblance alone can make histologic diagnosis difficult.

Do not diagnose the agent merely from a necrotic surface.

Slide 37 · From colonic invasion to liver abscess

Colonic wall invasion

Entry into splanchnic vessels

Hematogenous spread to liver

Liquefactive tissue destruction / abscess

Spread may follow clinically apparent or subsequently resolved intestinal illness.

Schematic sequence

Slide 38 · The amebic liver abscess is cell-poor at its edge

Liver lesions may contain extensive liquefied necrotic material.

The source describes scant inflammation at the margins.

The cavity may have a shaggy fibrinous lining.

Extensive destruction need not produce the dense neutrophilic ring of pyogenic pus.

Schematic

Liquefied necrotic material

Scant marginal cells

Slide 39 · Amebic necrosis: Clinical organ manifestations

Colonic disease may produce bloody diarrhea and abdominal pain.

Invasive disease can lead to acute necrotizing colitis and megacolon.

Hepatic abscesses can persist after the acute intestinal episode.

Rare direct extension to lung or heart and hematogenous spread to other sites are described.

Slide 40 · Amebic versus pyogenic tissue destruction

Amebic hepatic abscess

Pyogenic bacterial abscess

Principal injurious context

Parasite invasion and tissue destruction

Neutrophil-rich bacterial inflammation

Necrosis

Extensive liquefaction

Liquefaction forming pus

Inflammatory cells

Scant at lesion margins

Typically prominent

Morphologic limitation

Cannot infer all abscesses are bacterial

Pus does not indicate a unique species

Slide 41 · The unifying amebic teaching point

The parasite causes colonic ulcers and liver abscesses.

Both lesions arise through invasive tissue destruction.

Liquefactive necrosis can be prominent even when inflammatory infiltration is modest.

Lesion architecture and epidemiologic / clinical context matter alongside cell density.

Slide 42 · Viruses can cause severe tissue necrosis

Viral cell killing is not limited to minor cytopathic changes.

Some infections produce widespread host-cell necrosis with inflammation.

HSV destruction of temporal lobe tissue and HBV-related hepatic injury.

Viral injury can reflect direct cytopathic activity or antiviral immunity.

Slide 43 · Direct virus-induced cell injury

Viral entry and replication

Host macromolecule synthesis is altered

ER stress / toxic viral proteins or cytolysis

Death of infected cells

Direct mechanisms vary across viral families; This is a general pathway, not a claim for every virus.

Schematic sequence

Slide 44 · Antiviral immunity can also injure organs

Virus infects a host cell

Viral antigens are recognized

Cytotoxic T lymphocytes target infected cells

Host-cell death damages tissue

A protective immune response may simultaneously be the principal cause of organ injury.

Schematic sequence

Slide 45 · Direct cytopathy versus immune-mediated injury

Question

Direct viral effects

Host antiviral response

Immediate injurious agent

Viral replication or proteins

Immune effector cells

Target

Infected host cell

Virus-infected host cell

Teaching example

HSV-associated cytopathic injury

HBV hepatocyte injury via CD8⁺ T cells

Interpretation

Identify viral cell changes if visible

Consider immune infiltrate and cell injury

Slide 46 · HSV: From mucosal replication to CNS involvement

HSV-1 and HSV-2 replicate at mucocutaneous entry sites.

The viruses travel along sensory axons and establish latency in neuronal cell bodies.

HSV-1 encephalitis usually involves temporal lobes and orbital frontal gyri.

CNS infection may cause extensive destruction of involved brain tissue.

Slide 47 · HSV encephalitis: Regional vulnerability

Temporal lobes are characteristic sites emphasized.

The excerpt describes severe tissue destruction in these regions.

Location can be diagnostically informative but not independently definitive.

Schematic

Temporal regions

Slide 48 · HSV cytopathic morphology

HSV may form Cowdry type A intranuclear inclusions.

Nuclear chromatin is displaced to the periphery.

Infected cells can fuse into multinucleated syncytia.

The drawing conveys nuclear relationships only; It is not microphotography.

Schematic

Intranucl. Inclusion (schematic)

Slide 49 · HSV infection is not confined to the brain

Cutaneous and mucosal lesions may form vesicles and erosions.

Neonatal infection can involve necrotic foci in lungs, liver, adrenals and CNS.

Necrotizing HSV bronchopneumonia and hepatitis are described in disseminated infection.

Immunosuppression increases the importance of disseminated visceral HSV.

Slide 50 · HSV: Direct cytolysis and immune-related injury

Setting

Dominant teaching mechanism

Pathologic consequence

Epithelial keratitis

Direct viral cytolysis

Superficial epithelial damage

Stromal keratitis

Host immune reaction

Inflammation and later scarring

Encephalitis

Destructive viral infection

Severe regional CNS injury

Disseminated infection

Visceral involvement

Necrotic foci in organs

Slide 51 · HBV hepatocyte injury is largely immune-mediated

HBV infection may be cleared, persist, or occasionally produce acute hepatic failure.

Most hepatocyte injury is attributed to CD8⁺ cytotoxic T lymphocytes.

High viral replication can also cause some cytopathic changes.

The degree of immune response strongly affects disease outcome.

Slide 52 · HBV injury: Pathogenesis to liver failure

Hepatocytes carry HBV antigens

CD8⁺ T cells target infected hepatocytes

Hepatocyte death becomes extensive

Confluent / massive necrosis may cause liver failure

Avoid equating infection with inevitable liver failure; This is a severe possible outcome.

Schematic sequence

Slide 53 · Morphology of severe viral hepatitis

Acute viral hepatitis produces predominantly lymphocytic portal and lobular inflammation.

Hepatocytes can undergo necrosis or apoptosis.

Necrosis may become confluent, bridging or panlobular.

The liver may shrink in cases associated with acute liver failure.

Slide 54 · Progression from scattered to confluent injury

Isolated dying hepatocytes may coexist with otherwise viable plates.

Confluent necrosis indicates involvement of groups of hepatocytes.

Bridging necrosis links vascular structures; Panlobular necrosis spans a lobule.

These are patterns of extent, not separate pathogens.

Schematic

×

Scattered cell injury

×

×

×

×

×

×

Confluent groups

×

×

×

×

×

Widespread injury

× = necrotic cell (conceptual)

Slide 55 · Massive hepatic necrosis is an organ-level event

Extensive hepatocyte loss compromises functional liver parenchyma.

Acute hepatic failure with massive necrosis among HBV outcomes.

Necrosis can progress from groups of hepatocytes to entire lobules.

Severe anatomic destruction explains why fulminant hepatitis is clinically consequential.

Slide 56 · HSV and HBV: Do not equate mechanism

Dimension

HSV

HBV

Exemplar organ

Brain (temporal lobe)

Liver

Characteristic lesion

Severe regional destruction

Hepatocellular necrosis

Mechanistic emphasis

Viral cytopathic damage; inflammation

Mainly CTL-mediated hepatocyte injury

Diagnostic context

HSV cell changes / CNS localization

Portal-lobular hepatitis / serology

Slide 57 · Five exemplar agents: A mechanistic synthesis

Agent

Principal site

Destructive mechanism

C. perfringens

Muscle / wound

Phospholipase toxin + enzymes

C. diphtheriae

Airway epithelium

EF-2 inhibition by exotoxin

E. histolytica

Colon / liver

Protozoal invasion; liquefaction

HSV

CNS / other tissues

Viral cytopathy ± inflammation

HBV

Liver

Predominantly T-cell–mediated injury

Slide 58 · Reading a necrotizing infectious lesion

Determine which tissue is destroyed

Assess architecture and type of necrosis

Identify dominant inflammation or its absence

Correlate distribution with plausible pathogen

Necrosis is a pattern to be interpreted, not a stain-based species identification.

Schematic sequence

Slide 59 · Anatomic pattern is a major discriminator

Involved tissue

Key morphological clue

Exemplar

Skeletal muscle

Extensive myonecrosis; gas / thrombosis

Clostridial gas gangrene

Upper airway

Adherent necrotic pseudomembrane

Diphtheria

Colon

Narrow-neck, broad-base ulcer

Amebiasis

Liver abscess

Liquefaction, little edge inflammation

Amebiasis

Brain temporal region

Severe tissue destruction

HSV encephalitis

Slide 60 · Three cautions for morphology-based inference

Necrosis patterns are not uniquely attributable to one microorganism.

Multiple inflammatory patterns can coexist in one infected tissue.

The host immune state can markedly change cell recruitment and lesion morphology.

Clinical context and targeted organism identification remain essential.

Slide 61 · Case 1 · Rapidly destructive wound lesion

Following trauma, a patient develops rapidly progressive swollen muscle with bullae and gas within diseased tissue.

Histology shows marked muscle necrosis with relatively few neutrophils.

Question: Which causal mechanism best explains the dominant pathology?

Slide 62 · Case 1 · Mechanistic interpretation

The pattern points toward clostridial myonecrosis.

Anaerobic growth follows tissue devitalization.

C. Perfringens α-toxin damages membranes; Enzymes facilitate spread.

Extensive necrosis may be disproportionate to the neutrophilic infiltrate.

Slide 63 · Case 2 · Colonic ulcer and liver cavity

A patient with dysentery has a colonic ulcer with a narrow mucosal opening and broader deeper extension.

A liver cavity contains extensive liquefied tissue but little inflammation at its edge.

Question: Why does this pattern differ from a typical pyogenic abscess?

Slide 64 · Case 2 · Mechanistic interpretation

Invasive E. Histolytica produces a characteristic flask-shaped ulcer.

Vascular spread may seed the liver.

Amebic liver abscesses can have extensive necrosis with scant marginal inflammation.

Thus, liquefaction does not automatically mean neutrophil-rich bacterial pus.

Slide 65 · Case 3 · Adherent gray airway lesion

An upper-airway lesion displays a tough gray membrane over ulcerated mucosa.

Below the membrane there is a dense neutrophilic infiltrate and vascular congestion.

Question: Explain the epithelial death and the clinical risk of membrane separation.

Slide 66 · Case 3 · Mechanistic interpretation

C. Diphtheriae exotoxin blocks translation by inactivating EF-2.

Epithelial necrosis plus fibrinosuppurative exudate creates the pseudomembrane.

The membrane rests on inflamed, vascularized mucosa.

Sloughing may cause bleeding and airway compromise.

Slide 67 · Case 4 · Severe necrotizing viral injury

An infection severely injures temporal lobe tissue; Another patient has diffuse hepatocellular death with lymphocytic inflammation.

Question: Which exemplar viruses are described, and must their dominant cellular injury mechanism be identical?

Slide 68 · Case 4 · Mechanistic interpretation

Severe temporal lobe destruction is a classic HSV example.

Fulminant hepatic necrosis is a potential HBV-associated outcome.

HBV hepatocyte damage is mainly cytotoxic T-cell mediated.

Similar morphologic endpoints can result from different causal pathways.

Slide 69 · Integrative take-home points

Infectious tissue necrosis is a morphologic endpoint, not a diagnosis of species.

Microbial toxins, direct cytopathy and host immunity are distinct pathways to cell death.

Clostridial and amebic lesions can destroy tissue with sparse inflammation.

Correlate distribution, injury architecture, inflammatory cells and clinical context.

Slide 70 · Core source and cross-chapter context

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

Chapter 8: infectious tissue-reaction patterns and organism-specific pathology.

Chapter 2: morphology and patterns of tissue necrosis.

Chapter 17: Entamoeba histolytica colitis and hepatic abscess.

Chapter 18: viral hepatitis–related hepatocyte injury.