Acute Inflammation

Slide 1 · Acute Inflammation

Vascular and cellular mechanisms • mediators • tissue patterns • outcomes

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · What learners should be able to explain

Connect the three defining components to local signs of acute inflammation.

Trace neutrophils from circulation to tissue and intracellular microbial destruction.

Relate inflammatory mediators to specific vascular and cellular effects.

Distinguish major morphologic patterns and predict possible outcomes.

Slide 3 · Acute and chronic inflammation are distinct responses

Acute inflammation

Begins rapidly: Minutes to hours

Fluid exudation with predominantly neutrophils

Usually short-lived when stimulus is removed

Prominent local manifestations

Chronic inflammation

Longer time course

Macrophages and lymphocytes predominate

More sustained injury and fibrosis

Can coexist with acute inflammation

Slide 4 · The protective purpose—and the potential cost

The central task is to deliver defense molecules and leukocytes to the focus of injury.

Eliminate microbes, damaged cells, and foreign material.

Extravascular proteins and activated leukocytes improve local defense.

The same destructive products may damage surrounding healthy tissue.

Slide 5 · Inflammation follows five coordinated tasks

Recognition

Recruitment

Removal

Regulation

Repair

Inflammation does not end with leukocyte killing.

Shutoff and tissue recovery are integral to effective host defense.

Slide 6 · What can initiate an inflammatory response?

Infectious agents

Bacteria, fungi, and other microbes activate sensing pathways.

Tissue damage

Necrotic cells and tissue injury release alarm signals.

Other injurious stimuli

Foreign bodies, trauma, and immune reactions may elicit inflammation.

Slide 7 · Tissue sentinels detect the offending agent

Resident macrophages, dendritic cells, and mast cells respond before circulating neutrophils arrive.

Sentinel cells survey local tissue for microbes or abnormal material.

Recognition triggers cytokines, lipid mediators, and other signals.

Mediators recruit plasma proteins and circulating leukocytes.

Slide 8 · Recognition is translated into a vascular response

Microbes / necrotic cells

Resident sentinel cells

Locally released mediators

Microvascular activation

Early mediators act near the focus of injury.

Plasma and circulating cells then gain access to extravascular tissue.

Slide 9 · How innate receptors identify danger

Cellular receptors can recognize conserved microbial structures.

Sensors of cell injury respond to substances released by damaged cells.

Complement and other circulating proteins can identify microbes.

Recognition mechanisms initiate local effector pathways.

Slide 10 · Three defining components of acute inflammation

1. Vasodilation

Dilation of small vessels increases regional blood flow.

2. Vascular leakage

Microvascular permeability permits plasma proteins to enter tissue.

3. Leukocyte migration

Leukocytes exit blood, accumulate, and become activated.

Slide 11 · From detection to the inflamed tissue

Local danger recognized

Vasodilation / plasma leakage

Neutrophil recruitment

Elimination / resolution

Vascular and cellular events overlap in time.

The response becomes self-limited if the injurious stimulus disappears.

Slide 12 · The cardinal signs have mechanistic explanations

Clinical sign

Principal mechanism

Redness (rubor)

Vasodilation and vascular congestion

Heat (calor)

Increased local blood flow

Swelling (tumor)

Leakage and accumulation of edema fluid

Pain (dolor)

Inflammatory mediators and pressure

Loss of function

Pain and tissue injury

Clinical sign

Principal mechanism

Slide 13 · Why blood vessels matter in acute inflammation

Vessel lumen

Extravascular tissue

Inflammatory plasma proteins and leukocytes must cross the microvascular wall.

Slide 14 · Vasodilation is an early vascular event

Vasoactive mediators relax vascular smooth muscle and increase local perfusion.

Histamine is a major early mediator of vasodilation.

Small vessels, including arterioles, show increased flow.

Increased perfusion produces warmth and erythema.

Slide 15 · Loss of fluid promotes stasis and margination

Vessel lumen

Extravascular tissue

Leukocytes redistribute toward endothelial surface

Hemoconcentration and slower flow favor leukocyte contact with endothelium.

Slide 16 · Edema and exudation are not synonyms

Exudation is escape of fluid, proteins, and sometimes cells from blood vessels.

An exudate is protein-rich fluid produced by inflammatory vascular leakage.

Edema means increased interstitial or serous-cavity fluid, of either type.

A transudate results from hydrostatic or oncotic imbalance without increased permeability.

Slide 17 · Exudate versus transudate

Feature

Inflammatory exudate

Noninflammatory transudate

Protein content

Relatively high

Relatively low

Cellular material

May contain leukocytes / debris

Few or no cells

Mechanism

Microvascular permeability ↑

Hydrostatic / oncotic imbalance

Implication

Supports inflammation

May reflect systemic fluid imbalance

Feature

Inflammatory exudate

Noninflammatory transudate

Slide 18 · Leakage transfers plasma proteins into tissue

Vessel lumen

Extravascular tissue

Protein-rich fluid enters the tissue after endothelial barrier disruption

Fluid accumulation is a consequence of an altered endothelial barrier.

Slide 19 · Immediate transient permeability: Endothelial gaps

Histamine / bradykinin / leukotrienes

Endothelial contraction

Interendothelial gaps

Protein-rich exudate

The classic response is rapid and usually short-lived.

Postcapillary venules are a principal site of this leakage.

Slide 20 · Endothelial contraction and endothelial injury differ

Mediator-driven gap formation

Rapid onset following mediator release

Contraction creates intercellular openings

Often transient and reversible

Characteristic of histamine-associated leakage

Direct endothelial injury

Severe burns, toxins, or microbial damage

Necrosis and endothelial detachment

Potentially sustained vascular leakage

Can be amplified by recruited neutrophils

Slide 21 · Delayed and sustained vascular leakage

Not every permeability response is immediate and transient.

Some mild insults yield delayed leakage after several hours.

Direct endothelial damage produces longer-lasting barrier failure.

Multiple permeability mechanisms may coexist in the same injury.

Slide 22 · Local lymphatics respond to inflammation

Drain excess fluid

Lymphatics help remove edema fluid and restore interstitial balance.

Carry cellular material

Lymphatic channels carry inflammatory cells and microbial material.

Reactive nodes

Regional lymph nodes may enlarge as immune responses develop.

Slide 23 · The effector cells of acute inflammation

Neutrophils and macrophages are the dominant phagocytic cells.

They ingest microbes, necrotic cells, and other unwanted material.

Neutrophils arrive early and provide rapid antimicrobial activity.

Macrophages clear debris and contribute to subsequent repair.

Slide 24 · Leukocyte recruitment is a multistep cascade

Margination / rolling

Chemokine activation

Firm adhesion

Transmigration

After leaving the vessel, cells follow chemical gradients in tissue.

Cell adhesion is controlled by endothelial and leukocyte molecules.

Slide 25 · Margination brings leukocytes to the vessel wall

In rapidly flowing blood, red cells occupy the central axial stream.

Stasis redistributes leukocytes toward the endothelial surface.

Contact allows subsequent tethering and rolling interactions.

Slide 26 · Selectins mediate rolling, not stable arrest

Endothelial selectins

Activated endothelium displays P-selectin and E-selectin.

Leukocyte ligands

Carbohydrate-bearing ligands bind selectins transiently.

Functional outcome

Repeated weak attachments slow cells and produce rolling.

Slide 27 · Inflammatory cytokines activate endothelium

Injurious stimulus

Macrophage TNF / IL-1

Endothelial activation

Adhesion molecules ↑

The endothelial surface changes from antiadhesive to leukocyte-binding.

Chemokine display helps activate passing cells.

Slide 28 · Chemokines switch leukocyte integrins to high affinity

Rolling creates time for leukocytes to encounter endothelial chemokines.

Chemokine signals act through leukocyte G protein–coupled receptors.

Inside-out signaling increases the binding capacity of integrins.

Activated integrins interact strongly with endothelial ligands.

Slide 29 · Stable adhesion requires integrins and endothelial ligands

Leukocyte surface

High-affinity integrins such as LFA-1 and Mac-1 bind firmly.

Endothelial surface

Immunoglobulin-family ligands include ICAM-1.

Result

Neutrophils stop rolling and prepare to cross the vessel wall.

Slide 30 · Transmigration: Crossing a postcapillary venule

Vessel lumen

Extravascular tissue

Rolling

Firm adhesion

Diapedesis

PECAM-1 (CD31) participates in junctional migration; Basement membrane is traversed.

Slide 31 · Chemotaxis directs cells within the tissue

Chemotaxis is directed migration along a concentration gradient.

Chemoattractants activate leukocyte G protein–coupled receptors.

Actin polymerization at the leading edge drives cell movement.

The gradient directs cells toward microbes or damaged tissue.

Slide 32 · Major chemoattractants for neutrophils

Source

Representative chemoattractant

Consequence

Bacteria

N-formylated peptides

Directed migration

Chemokines

IL-8 / CXCL8

Chemotaxis and activation

Complement

C5a

Chemotaxis and activation

Arachidonic acid

LTB4

Chemotaxis and activation

Source

Representative chemoattractant

Consequence

Slide 33 · Early neutrophils and later macrophages

Neutrophils

Commonly dominate at 6–24 hours

Rapidly recruited, numerous in blood

Short lifespan; Undergo apoptosis

Strong phagocytic and microbicidal response

Monocytes / macrophages

Often increase at 24–48 hours

Differentiate into tissue macrophages

Can persist and proliferate locally

Clear debris and support tissue repair

Slide 34 · The cellular timeline is stimulus-dependent

The neutrophil-to-macrophage sequence is a useful pattern—not a rigid rule.

Some bacterial infections sustain neutrophilic recruitment.

Lymphocytes can appear early in viral inflammation.

Eosinophils may predominate with helminths and some allergies.

Interpret cellular composition together with time and etiology.

Slide 35 · Leukocyte activation follows recognition

Microbial or host products

Leukocyte receptors

Intracellular signaling

Phagocytosis / killing

Different receptors converge on effector functions.

Activation can also provoke extracellular mediator release.

Slide 36 · Phagocytosis has three sequential stages

Recognition / binding

Engulfment

Phagolysosome formation

Killing / degradation

Efficient ingestion usually depends on surface receptors and opsonins.

Slide 37 · Opsonins improve phagocytic recognition

Opsonins coat particles and enhance binding to phagocytes.

Major opsonins include IgG, C3b/iC3b, and plasma lectins.

Phagocytes express receptors that recognize these bound molecules.

Receptor-mediated binding triggers engulfment.

Slide 38 · How a phagosome becomes a destructive compartment

Microbe binds receptor

Membrane surrounds target

Phagosome closes

Lysosome fuses

The resulting phagolysosome concentrates microbicidal mechanisms.

Actin remodeling is required for engulfment.

Slide 39 · Three main intracellular killing systems

Reactive oxygen species

NADPH oxidase initiates oxygen radical generation.

Reactive nitrogen species

Inducible nitric oxide synthase contributes reactive nitrogen products.

Lysosomal components

Granule enzymes and antimicrobial proteins degrade ingested targets.

Slide 40 · Respiratory burst: NADPH oxidase pathway

Phagocyte NADPH oxidase

Superoxide (O₂•−)

Hydrogen peroxide (H₂O₂)

Oxidative killing

Assembly of oxidase components follows phagocyte activation.

The respiratory burst increases cellular oxygen consumption.

Slide 41 · Myeloperoxidase creates a potent microbicidal oxidant

H₂O₂

MPO + chloride

Hypochlorite (OCl−)

Microbial damage

Myeloperoxidase is abundant in neutrophil azurophilic granules.

MPO deficiency alone has limited clinical impact because killing systems overlap.

Slide 42 · Nitric oxide contributes to microbial killing

Macrophage activation

Inducible NOS (iNOS)

Nitric oxide (NO)

Reactive nitrogen intermediates

NO can react with superoxide to form peroxynitrite.

These reactive species damage microbial proteins, lipids, and nucleic acids.

Slide 43 · Lysosomal enzymes require controlled compartmentalization

Microbicidal molecules are effective—but potentially destructive to host cells.

Lysosomes fuse with phagosomes to deliver degradative enzymes.

Acid hydrolases and granule components participate in digestion.

Extracellular release can damage nearby tissue.

Slide 44 · Neutrophil extracellular traps (NETs)

DNA-based scaffold

Activated neutrophils may release chromatin as extracellular traps.

Antimicrobial components

Microbes can be trapped together with granule antimicrobial proteins.

Potential cost

Extracellular neutrophil products can contribute to host injury.

Slide 45 · Why host defense can injure normal tissue

Activated leukocyte

Extracellular ROS / enzymes

Bystander cell injury

Amplified inflammation

Collateral damage is a recognized cost of microbial elimination.

Excessive or misdirected responses can dominate the disease process.

Slide 46 · Inflammatory mediators come from two sources

Preformed cell stores

Histamine can be released rapidly from mast-cell granules.

New cell synthesis

Cytokines and eicosanoids are generated after stimulation.

Plasma precursors

Complement and kinin pathways are activated from circulating precursors.

Slide 47 · Mediator networks amplify and restrain inflammation

Inflammatory mediators are not simply “on/off” signals.

One mediator can provoke release of additional mediators.

Different mediators often have overlapping actions.

Short half-lives and enzymatic inactivation restrict their effects.

Opposing mediators actively limit the response.

Slide 48 · Histamine links mast-cell activation to vascular change

Mast-cell degranulation

Histamine release

Arteriolar dilation + venular gaps

Warmth + exudation

Antigen-bound IgE and complement fragments can provoke degranulation.

Histamine acts prominently through H1 receptors.

Slide 49 · Arachidonic acid generates different mediator families

Membrane phospholipids

Arachidonic acid

COX / lipoxygenase paths

Distinct eicosanoids

Prostaglandins, thromboxane, leukotrienes, and lipoxins have different effects.

Enzyme branch determines biological output.

Slide 50 · Prostaglandins: Selected inflammatory effects

Mediator group

Principal effect

Clinicopathologic relation

PGE₂

Pain sensitization; fever

Pain and elevated temperature

PGI₂ / PGD₂

Vasodilation

Increased flow / redness

Thromboxane A₂

Vasoconstriction; platelet effects

Vascular / hemostatic interface

Mediator group

Principal effect

Clinicopathologic relation

Slide 51 · Leukotrienes have distinct cellular and vascular actions

Mediator

Major effect

Interpretation

LTB₄

Neutrophil chemotaxis and activation

Recruitment toward inflammatory focus

LTC₄ / LTD₄ / LTE₄

Increased permeability

Exudation

LTC₄ / LTD₄ / LTE₄

Bronchoconstriction

Airway reaction in asthma

Mediator

Major effect

Interpretation

Slide 52 · Lipoxins help restrain further neutrophil influx

Arachidonic acid metabolites can also be anti-inflammatory.

Lipoxins inhibit neutrophil adhesion to endothelium.

They reduce neutrophil chemotaxis.

A change toward resolving mediators supports termination.

Slide 53 · TNF and IL-1 coordinate leukocyte recruitment

Activated macrophages / dendritic cells

TNF + IL-1

Endothelial activation

Adhesion and migration

They also stimulate other cells and contribute to systemic inflammation.

TNF and IL-1 are powerful but potentially harmful cytokine signals.

Slide 54 · Chemokines provide positional information

Inflammatory chemokines form gradients that guide migrating cells.

Chemokines presented on endothelial surfaces promote integrin activation.

Chemokine receptors transmit signals that reorganize cell motility.

Slide 55 · Complement activation converges on C3

Classical / alternative / lectin

C3 convertase

C3a + C3b

C5 convertase / terminal pathway

The pathways have different triggers but share central effector steps.

Complement proteins circulate as inactive precursor molecules.

Slide 56 · Complement has three major effector functions

Inflammation

C3a and C5a stimulate vascular reactions; C5a attracts leukocytes.

Opsonization

C3b and iC3b coat microbes and enhance phagocytosis.

Cell lysis

C5b–C9 forms the membrane attack complex on susceptible microbes.

Slide 57 · Mediator-to-effect map for acute inflammation

Inflammatory event

Important mediator examples

Vasodilation

Histamine; prostaglandins

Permeability ↑

Histamine; bradykinin; LTC₄/LTD₄/LTE₄

Neutrophil chemotaxis

C5a; IL-8 / CXCL8; LTB₄

Endothelial activation

TNF; IL-1

Pain / fever

Bradykinin and prostaglandins; cytokine effects

Inflammatory event

Important mediator examples

Slide 58 · Other soluble mediators extend the network

Plasma precursor pathways

Kinins / complement

Vascular / leukocyte effects

Local inflammatory response

Bradykinin promotes vascular permeability and pain.

Multiple mediators may operate simultaneously at a single site.

Slide 59 · Morphology reflects the dominant tissue reaction

Dilated vessels

Congestion produces a visibly hyperemic focus.

Extravascular fluid

Edema results when fluid accumulates outside vessels.

Leukocyte infiltrate

Typically, neutrophils dominate early acute tissue inflammation.

Slide 60 · Serous inflammation: Fluid-rich, cell-poor reaction

Serous fluid

Clear fluid

Fluid accumulation with few leukocytes

Schematic — not a tissue micrograph

Slide 61 · The serous pattern requires context

Serous fluid may accumulate in a blister after skin injury.

Serous-cavity effusions may arise from inflammatory leakage or mesothelial secretion.

An effusion is not automatically inflammatory: Noninflammatory causes also exist.

Slide 62 · Fibrinous inflammation: Plasma fibrinogen escapes

Fibrin deposition

Fibrinogen leakage → extracellular fibrin

Schematic — not a tissue micrograph

Slide 63 · Fibrinous exudate can resolve—or organize

Substantial vascular leakage

Extravascular fibrin

Fibrinolysis / macrophage removal

Resolution or organization

Persistent fibrin promotes fibroblast and vascular ingrowth.

Organization can produce fibrous adhesions or serosal thickening.

Slide 64 · Purulent inflammation: Pus and liquefactive necrosis

Suppurative focus

Neutrophils + liquefied necrotic debris

Schematic — not a tissue micrograph

Slide 65 · Abscess: A localized collection of pus

Pyogenic organisms can trigger local suppuration.

Central necrotic fluid contains dead leukocytes and tissue debris.

A neutrophil-rich zone and reactive vascular changes often surround it.

Later organization may wall off the lesion and leave fibrous tissue.

Slide 66 · An ulcer requires necrosis at or near a surface

Surface loss

Sloughing of inflamed necrotic tissue

Schematic — not a tissue micrograph

Slide 67 · Morphologic patterns: What distinguishes them?

Pattern

Dominant feature

Example in source

Serous

Relatively cell-poor fluid

Skin blister

Fibrinous

Fibrin-rich surface / cavity exudate

Pericarditis

Purulent

Neutrophils + necrotic debris

Acute appendicitis / abscess

Ulcerative

Surface tissue loss after necrosis

Peptic ulcer

Pattern

Dominant feature

Example in source

Slide 68 · Acute inflammation has three broad outcomes

Complete resolution

Stimulus eliminated; Debris and fluid cleared; Tissue regenerates.

Healing with fibrosis

Severe injury, nonregenerating tissue, or persistent fibrin becomes scar.

Chronic inflammation

Failure to eliminate the stimulus sustains the inflammatory reaction.

Slide 69 · Resolution requires coordinated cleanup

Offending agent removed

Neutrophil apoptosis

Macrophage clearance

Edema resorption / regeneration

Resolution is most likely after limited, short-lived injury.

Tissue structure and function can return toward normal.

Slide 70 · Fibrosis follows damage that cannot fully regenerate

Substantial tissue injury

Persistent fibrin / matrix damage

Fibroblast + vessel ingrowth

Organization and scar

A fibrovascular response replaces tissue that cannot be restored.

Serosal fibrin may organize into adhesions.

Slide 71 · Persistence can convert acute into chronic inflammation

Failure of stimulus elimination prevents complete resolution.

A persistent agent can sustain macrophage recruitment and activation.

Acute and chronic cell populations may overlap within lesions.

Long-standing injury may progress to tissue destruction and fibrosis.

Slide 72 · Active signals help terminate the acute response

Stimulus decreases

Mediator production wanes

IL-10 / TGF-β / lipoxins

Inflammatory activity declines

Short-lived neutrophils also disappear by apoptosis.

The termination program limits collateral tissue injury.

Slide 73 · Clinical application: A superficial blister

A patient develops a fluid-filled blister after a mild burn, without a thick purulent exudate.

What morphologic pattern is most likely?

Why can clear fluid accumulate beneath a damaged epithelial surface?

What additional finding would suggest suppurative inflammation?

Slide 74 · Clinical application: A localized abscess

A tissue lesion contains a central liquefied focus rich in neutrophils and cell debris.

Identify the inflammatory pattern and the term for the localized collection.

Explain how neutrophil products contribute to central tissue liquefaction.

Predict one potential later outcome if tissue destruction is extensive.

Slide 75 · Apply the vascular–cellular sequence

An acutely inflamed venule becomes congested, and neutrophils begin adhering to its endothelial surface.

What hemodynamic change favors neutrophil margination?

Distinguish molecules responsible for rolling and stable adhesion.

Name the migration step mediated in part by PECAM-1.

Slide 76 · Clinical findings can be traced back to mechanism

Red + warm

Vasodilation increases blood flow and causes vascular congestion.

Swollen + painful

Permeability, edema, and inflammatory mediators cause these manifestations.

Neutrophil-rich

Leukocyte recruitment followed by activation produces neutrophilic exudation.

Slide 77 · Acute inflammation, integrated

Detect danger

Deliver plasma + leukocytes

Phagocytose / destroy

Terminate or persist

Mechanisms are protective when spatially and temporally controlled.

Persistent stimuli or extensive tissue injury alter the outcome.

Slide 78 · Core concepts to retain

The vascular triad is dilation, increased permeability, and leukocyte recruitment.

Selectins → chemokine-mediated integrin activation → adhesion → diapedesis.

Phagocytes use ROS, reactive nitrogen species, and lysosomal components.

The tissue result is resolution, fibrosis, or chronic inflammation.

Slide 79 · Primary reference

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

Chapter 3: Inflammation and Repair.

Acute inflammation and connected vascular, leukocyte, mediator, morphology, and outcome sections.