Summary of Acute Inflammation

Slide 1 · Summary of Acute Inflammation

An integrated clinicopathologic review

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Vessels

Leukocytes

Mediators

Resolution

Schematic

Connect vascular and cellular events to clinical signs.

Explain recruitment, killing, and mediator effects.

Distinguish morphologic patterns and major outcomes.

Slide 3 · Inflammation follows five coordinated responses

Recognize

Recruit

Remove

Regulate

Repair

Schematic

Recognition initiates the response to injurious stimuli.

Recruitment and removal provide antimicrobial and cleanup functions.

Regulation and repair limit collateral damage.

Slide 4 · Acute inflammation has three major components

Vasodilation

Permeability

Leukocyte activation

Schematic

Small-vessel dilation increases regional blood flow.

Increased permeability transfers protein-rich fluid into tissue.

Leukocytes exit vessels and become activated at the focus.

Slide 5 · The response begins with microbes or injured cells

Microbes / injured cells

Sentinel recognition

Mediator release

Schematic

Infections and necrotic tissues are important initiating stimuli.

Resident phagocytes attempt immediate elimination.

Sentinel cells release mediators when they sense abnormalities.

Slide 6 · Inflammatory stimuli are heterogeneous

Acute

Inflammation

Infection

Necrosis

Foreign body

Trauma

Immune response

Schematic

Inflammation can follow infection or tissue necrosis.

Foreign bodies and trauma also provoke inflammation.

Immune responses can induce inflammation and tissue injury.

Slide 7 · Sentinel cells connect recognition to effector responses

Tissue sentinel cells

Cytokines / lipids

Vessels + leukocytes

Schematic

Resident phagocytes and other tissue cells detect danger.

These cells produce cytokines and lipid mediators.

Local mediators act on vessels and recruit leukocytes.

Slide 8 · Microbial and damage signals activate leukocytes

Agent / damage

Activation

Phagocytosis

Schematic

Microbial products and products of injured cells stimulate recruited cells.

Local mediators reinforce leukocyte activation.

Activated phagocytes ingest and destroy the offending material.

Slide 9 · Vascular and cellular reactions operate together

Vascular arm

Flow, permeability, endothelial activation

Cellular arm

Adhesion, migration, phagocytosis

Schematic

Vascular responses deliver plasma proteins to affected tissue.

Endothelial activation facilitates circulating cell recruitment.

Migrating leukocytes perform the principal removal functions.

Slide 10 · Vasodilation increases local blood flow

Lumen

Wider lumen

Increased flow

Warmth + redness

Schematic

Histamine acts early on vascular smooth muscle.

Vasodilation increases inflow into the inflamed area.

The resulting hyperemia contributes to warmth and redness.

Slide 11 · Vascular leakage delivers plasma proteins

Endothelial gaps

Protein leakage

Tissue edema

Schematic

Inflammatory mediators increase endothelial permeability.

Protein-rich exudate escapes into the interstitial space.

The same process contributes to tissue swelling.

Slide 12 · Endothelial gaps are a common cause of leakage

Chemical mediators

Endothelial gaps

Exudation

Schematic

Endothelial contraction opens intercellular gaps.

Histamine, bradykinin, and leukotrienes can induce contraction.

This response usually occurs rapidly and is transient.

Slide 13 · Direct endothelial injury can sustain leakage

Severe injury

Endothelial damage

Sustained leakage

Schematic

Severe injuries can produce endothelial necrosis and detachment.

Microbes and toxins may damage endothelium directly.

Adherent neutrophils can further amplify endothelial damage.

Slide 14 · Inflammatory exudate differs from transudate

Feature

Exudate

Transudate

Mechanism

Permeability increase

Hydrostatic / oncotic imbalance

Protein

Relatively high

Relatively low

Cells / debris

May be present

Little or none

Exudate implies increased vascular permeability.

Transudate reflects hydrostatic or oncotic imbalance without inflammation-driven permeability.

The mechanisms—not merely the presence of edema—distinguish them.

Slide 15 · Edema describes excess fluid, not its cause

Inflammatory edema

Vascular leakage → protein-rich exudate

Noninflammatory edema

Pressure imbalance → transudate

Schematic

Edema may occur in interstitial tissue or serous cavities.

Inflammatory edema often contains protein-rich exudate.

Noninflammatory processes can also produce edema.

Slide 16 · Fluid loss slows blood flow and promotes stasis

Plasma leakage

Hemoconcentration

Stasis

Margination

Schematic

Leakage decreases the fluid component within vessels.

Microvascular blood becomes concentrated and flows more slowly.

Stasis increases contact between circulating leukocytes and endothelium.

Slide 17 · Stasis prepares the endothelium–leukocyte interface

Lumen

Stasis

Margination

Adhesion

Schematic

In flowing blood, leukocytes tend to be displaced toward vessel walls.

Activated endothelium expresses adhesive molecules.

These changes enable rolling and subsequent firm adhesion.

Slide 18 · Leukocyte recruitment is a multistep journey

Margination

Rolling

Firm adhesion

Transmigration

Chemotaxis

Schematic

Cells first marginated, roll, and adhere to the endothelium.

They then cross the vessel wall.

They follow chemotactic signals to the injured tissue.

Slide 19 · Margination brings leukocytes close to the vessel wall

Lumen

Central red cells

Peripheral leukocytes

Activated wall

Schematic

Slower microvascular flow favors peripheral displacement of leukocytes.

Endothelial surfaces become receptive to binding.

Margination precedes selectin-mediated rolling.

Slide 20 · Rolling depends predominantly on selectins

Selectin binding

Transient adhesion

Rolling

Schematic

Selectins mediate relatively weak, reversible cell attachment.

Repeated adhesion and release produce rolling movement.

Rolling creates time for leukocyte activation at inflamed endothelium.

Slide 21 · Chemokines activate leukocyte integrins

Chemokine signal

Integrin activation

Firm adhesion

Schematic

Endothelium displays chemokines to rolling leukocytes.

Chemokine signaling increases integrin binding capacity.

Activated integrins prepare the cell for stable adhesion.

Slide 22 · Firm adhesion depends predominantly on integrins

Rolling

Selectins • transient contacts

Adhesion

Integrins • stable binding

Schematic

High-affinity leukocyte integrins bind endothelial ligands.

ICAM-1 is an important endothelial integrin ligand.

TNF and IL-1 promote endothelial activation and recruitment.

Slide 23 · Diapedesis moves leukocytes across endothelium

Adherent leukocyte

PECAM-1 junction

Extravascular migration

Schematic

Transmigration occurs mainly in postcapillary venules.

Junctional molecules include PECAM-1 (CD31).

Cells cross the basement membrane and enter tissue.

Slide 24 · Chemotaxis directs cells toward the stimulus

Low chemoattractant

Higher concentration

Injury focus

Schematic

Leukocytes migrate along chemical concentration gradients.

Leading-edge actin polymerization supports cell movement.

Direction is toward infection, tissue damage, and chemoattractants.

Slide 25 · Several signals attract leukocytes

Acute

Inflammation

Microbial products

Chemokines

C5a

LTB₄

Schematic

Bacterial products provide exogenous chemoattractants.

Chemokines such as CXCL8/IL-8 act locally.

Complement C5a and leukotriene B₄ are endogenous attractants.

Slide 26 · Neutrophils typically precede macrophages

Early: Neutrophils

Later: Monocytes

Persistent: Macrophages

Schematic

Neutrophils commonly predominate during the first 6–24 hours.

Monocytes become more prominent in the next 24–48 hours.

The infiltrate varies with the agent and duration of inflammation.

Slide 27 · Macrophages also support tissue repair

Clear debris

Produce growth factors

Promote repair

Schematic

Neutrophils and macrophages ingest microbes and dead tissue.

Macrophages persist longer in many inflammatory settings.

Macrophage-derived growth factors contribute to repair.

Slide 28 · Phagocytosis proceeds through three linked steps

Recognition

Engulfment

Killing + digestion

Schematic

A phagocyte recognizes and attaches to a target.

Engulfment creates a membrane-bound phagosome.

Microbial killing and digestion follow.

Slide 29 · Opsonization improves phagocyte recognition

IgG

C3b / iC3b

Plasma lectins

Schematic

IgG antibodies are important opsonins.

Complement C3b/iC3b enhances uptake.

Plasma lectins can also coat microbes for recognition.

Slide 30 · The phagolysosome localizes destructive products

Microbe

Phagosome

Phagolysosome

Schematic

Cytoplasmic extensions enclose the ingested target.

Phagosomes fuse with lysosomal compartments.

Destructive enzymes are concentrated around the ingested material.

Slide 31 · Reactive oxygen species participate in killing

Oxidase activation

Reactive oxygen species

Microbial injury

Schematic

Activation of phagocyte oxidase generates reactive oxygen intermediates.

These products act in intracellular antimicrobial compartments.

Antioxidant defenses help limit oxidative injury to host cells.

Slide 32 · Nitric oxide and enzymes add antimicrobial activity

Nitric oxide

Nitrogen radicals

Lysosomal enzymes

Schematic

Inducible nitric oxide synthase generates NO in activated phagocytes.

Nitrogen-derived intermediates damage microbial constituents.

Lysosomal enzymes degrade ingested material.

Slide 33 · Leukocyte products can also injure host tissue

Microbial clearance

Collateral injury

Schematic

Released proteases and reactive intermediates damage normal tissue.

Phagocytic defense therefore carries an injury risk.

Collateral damage can amplify the inflammatory reaction.

Slide 34 · Excess leukocyte activation perpetuates injury

Leukocyte activation

Toxic product release

Tissue injury

More inflammation

Schematic

Persistently activated leukocytes release inflammatory mediators.

Extracellular release of toxic metabolites is not target-specific.

Tissue damage can generate new inflammatory stimuli.

Slide 35 · Mediators convert recognition into visible inflammation

Acute

Inflammation

Histamine

Eicosanoids

Cytokines

Complement

Kinins

Schematic

Cell-derived mediators act locally on vessels and leukocytes.

Plasma-derived systems generate biologically active fragments.

Multiple mediators may reinforce or oppose one another.

Slide 36 · Histamine is an early vascular mediator

Mast cell activation

Histamine

Dilation + leakage

Schematic

Mast cells contain preformed histamine near vessels.

Histamine promotes arteriolar dilation and venular permeability.

Mast cell degranulation may be triggered by injury or complement.

Slide 37 · Eicosanoids coordinate several inflammatory effects

Prostaglandins

Leukotrienes

Lipoxins

Schematic

Arachidonic acid is converted into prostaglandins and leukotrienes.

Different eicosanoids alter vessels, leukocyte responses, and pain.

Lipoxins counterbalance selected proinflammatory effects.

Slide 38 · Prostaglandins contribute to pain and fever

Prostaglandin synthesis

Vascular / sensory effects

Pain + fever

Schematic

Prostaglandins participate in inflammatory vascular reactions.

PGE₂ is associated with pain sensitization and fever.

Mediator effects depend on the specific prostaglandin species.

Slide 39 · Leukotrienes have distinct functions

LTB₄

Leukocyte chemotaxis and activation

LTC₄ / LTD₄ / LTE₄

Vascular leakage and smooth-muscle effects

Schematic

LTB₄ promotes leukocyte recruitment and activation.

LTC₄, LTD₄, and LTE₄ increase vascular permeability.

Their effects differ from prostaglandin-mediated responses.

Slide 40 · Lipoxins help constrain neutrophil recruitment

Proinflammatory signals

Lipid mediator switch

Reduced recruitment

Schematic

A switch toward lipoxin synthesis is a termination mechanism.

Lipoxins antagonize selected leukotriene effects.

Regulation is active—not simply exhaustion of mediators.

Slide 41 · TNF and IL-1 activate endothelial recruitment machinery

Macrophage signals

TNF + IL-1

Endothelial activation

Schematic

Activated macrophages and other cells produce TNF and IL-1.

Both promote endothelial adhesion molecule expression.

Their effects enhance leukocyte adhesion and emigration.

Slide 42 · Chemokines provide both activation and direction

CXCL8 and others

Adhesion activation

Tissue chemotaxis

Schematic

CXCL8/IL-8 attracts and activates neutrophils.

Chemokines increase integrin binding during recruitment.

Chemokine gradients direct migration through tissue.

Slide 43 · Complement links recognition and elimination

C3a / C5a

C3b / iC3b

C5b–9

Schematic

C3a and C5a can augment vascular inflammation.

C5a attracts leukocytes; C3b/iC3b serves as an opsonin.

Terminal complement components can cause membrane lysis.

Slide 44 · Bradykinin connects vascular leakage and pain

Kinin generation

Vascular effects

Pain

Schematic

Kinin activation generates inflammatory peptides.

Bradykinin acts on the vasculature and contributes to pain.

It is one of several mediators responsible for local symptoms.

Slide 45 · Multiple mediators converge on the same endpoints

Effect

Representative mediators

Vasodilation

Histamine

Permeability

Histamine; LTC₄ / LTD₄ / LTE₄

Recruitment

TNF; IL-1; chemokines; C5a; LTB₄

Pain

Prostaglandins; bradykinin

Histamine and leukotrienes can increase leakage.

TNF, IL-1, and chemokines regulate recruitment.

Prostaglandins and bradykinin contribute to pain.

Slide 46 · The cardinal signs express vascular and cellular events

Acute

Inflammation

Rubor

Calor

Tumor

Dolor

Functio laesa

Schematic

Rubor and calor principally reflect increased regional blood flow.

Tumor reflects accumulation of extravascular fluid.

Dolor and functio laesa arise from pain and tissue injury.

Slide 47 · Redness and warmth reflect hyperemia

Vasodilation

Hyperemia

Rubor + calor

Schematic

Small vessels dilate in response to inflammatory mediators.

Increased local perfusion produces erythema and warmth.

This finding represents a vascular response rather than pus formation.

Slide 48 · Swelling reflects extravascular fluid accumulation

Leakage

Exudate

Edema (tumor)

Schematic

Permeable small vessels permit protein-rich fluid escape.

Fluid accumulates in interstitial spaces as edema.

Swelling can limit the mechanical function of affected tissues.

Slide 49 · Pain and lost function have multiple causes

Inflammation + damage

Pain (dolor)

Impaired function

Schematic

Prostaglandins, neuropeptides, and cytokines contribute to pain.

Damage to tissue also generates nociceptive stimuli.

Loss of function follows from pain and structural injury.

Slide 50 · Microscopy reflects vessels, fluid, and leukocytes

Dilated vessels

Extravascular fluid

Neutrophils

Schematic

Dilated small vessels are a cardinal morphologic feature.

Extravascular fluid accumulates in inflamed tissues.

Neutrophils commonly dominate early cellular infiltrates.

Slide 51 · Serous inflammation produces relatively cell-poor fluid

Surface injury

Fluid collection

Serous pattern

Simplified schematic; Not a tissue micrograph

Serous exudation may create a blister or a body-cavity effusion.

Such fluid generally lacks large numbers of leukocytes or microbes.

A skin blister from a burn is a classic morphologic example.

Slide 52 · Fibrinous inflammation deposits fibrin

Fibrinogen leakage

Fibrin deposition

Clearance or scar

Simplified schematic; Not a tissue micrograph

Greater permeability permits plasma fibrinogen to escape.

Fibrin may collect on serosal surfaces, including pericardium.

Persistent fibrin may organize into fibrous tissue.

Slide 53 · Purulent inflammation creates pus

Pyogenic injury

Neutrophil-rich exudate

Pus

Simplified schematic; Not a tissue micrograph

Pus contains neutrophils and liquefied necrotic debris.

Pyogenic bacteria frequently cause this pattern.

Acute appendicitis is a common example of suppurative inflammation.

Slide 54 · An abscess is localized suppurative inflammation

Liquefied center

Neutrophil zone

Reactive periphery

Concentric schematic; Not a specimen

An abscess contains a central liquefied region.

Viable neutrophils often surround the necrotic center.

Peripheral inflammation and repair may subsequently wall off the lesion.

Slide 55 · Ulceration combines surface loss with inflammation

Epithelial defect

Surface necrosis

Tissue loss

Inflammatory base

Simplified schematic; Not a tissue micrograph

An ulcer is a surface defect caused by sloughing of necrotic tissue.

Acute inflammation may occur at its base.

With chronicity, inflammatory cells and fibrosis can develop.

Slide 56 · The morphology helps infer the process

Pattern

Dominant material

Typical teaching example

Serous

Relatively cell-poor fluid

Skin blister

Fibrinous

Fibrin-rich exudate

Fibrinous pericarditis

Purulent

Pus: neutrophils + debris

Abscess / appendicitis

Serous exudates emphasize fluid accumulation.

Fibrinous exudates indicate conspicuous fibrin deposition.

Purulent processes feature neutrophil-rich exudate and necrotic debris.

Slide 57 · Three major outcomes follow an acute reaction

Acute inflammation

Resolution

Scar

Chronic response

Schematic

Elimination and adequate regeneration permit resolution.

Severe damage or unreabsorbed fibrin may lead to fibrosis.

Persistence of the stimulus can produce chronic inflammation.

Slide 58 · Complete resolution restores tissue architecture

Agent removed

Debris + edema cleared

Regeneration

Schematic

Macrophages clear microbes and cellular debris.

Lymphatics remove edema fluid from affected tissue.

Viable parenchymal cells regenerate if regenerative capacity is adequate.

Slide 59 · Fibrosis replaces tissue that cannot regenerate

Persistent damaged area

Organization

Scar

Schematic

Extensive destruction prevents simple restoration.

Uncleared fibrin may become organized.

Fibroblast and vessel ingrowth leads to fibrous scar formation.

Slide 60 · Persistent injury can convert acute into chronic inflammation

Unresolved cause

Continued recruitment

Chronic inflammation

Schematic

The offending stimulus may resist elimination.

Normal healing may be interrupted or ineffective.

Persistent inflammation combines damage and ongoing repair.

Slide 61 · Resolution requires active antiinflammatory signals

Mediator decay

Neutrophil apoptosis

IL-10 / TGF-β / lipoxins

Schematic

Stimulus disappearance limits new mediator production.

Neutrophils are short-lived and undergo apoptosis.

Lipoxins, IL-10, and TGF-β contribute to inhibition of inflammation.

Slide 62 · Host protection and tissue injury coexist

Protective removal

Collateral tissue injury

Schematic

Inflammation is beneficial when it removes offending agents.

The same antimicrobial products can injure host structures.

The ultimate outcome depends on the stimulus, damage, and regulation.

Slide 63 · Application: Why does an acutely infected wound swell?

Microbial stimulus

Vascular leakage

Edema

Schematic

Injury-associated mediators increase microvascular permeability.

Protein-rich plasma fluid enters the affected tissue.

The exudate produces local edema and contributes to dysfunction.

Slide 64 · Application: What makes an abscess purulent?

Bacterial injury

Suppuration

Localized abscess

Schematic

Pyogenic infection initiates neutrophil recruitment.

Necrotic cells and neutrophils contribute to liquefied debris.

The localized collection of pus defines an abscess.

Slide 65 · Application: Why can inflammation leave a scar?

Substantial injury

Fibrovascular ingrowth

Fibrous scar

Schematic

Deep tissue destruction may exceed regenerative capacity.

Persistent fibrin or damaged extracellular space becomes organized.

Connective tissue fills the defect, potentially impairing function.

Slide 66 · Integrated cascade: From injury to outcome

Recognition

Vascular response

Recruitment

Elimination

Regulation / outcome

Schematic

Sentinel-cell mediators initiate vascular changes and leukocyte entry.

Activated leukocytes phagocytose agents but may also injure tissue.

Successful control ends in resolution; Persistent damage changes the outcome.

Slide 67 · The five Rs unify the acute inflammatory response

Recognition

Recruitment

Removal

Regulation

Repair

Schematic

Recognition initiates mediator-driven vascular changes.

Recruitment and removal clear injurious agents and necrotic debris.

Regulation and repair restore homeostasis or expose failure of resolution.

Slide 68 · Summary: what to retain for clinicopathologic reasoning

Mechanism

Morphology

Outcome

Schematic

Vasodilation + leakage + leukocytes explain the core reaction.

Selectins, integrins, chemokines, and phagocytic mechanisms connect cause to morphology.

Morphology and persistence of injury help predict resolution, fibrosis, or chronicity.