Acute Inflammation

Dr. Abdul Wahed

MD (Pathology)
Lecturer
Sheikh Hasina Medical College Tangail
 Objectives
At the end of the session we will be able to-
1. know definition & cardinal signs of acute inflammation.
2. learn advantages & disadvantages of acute inflammation.
3. learn the changes in acute inflammation.
4. learn in details about mechanism of the changes.
5. know about the mediators of acute inflammation.
6. learn in details about phagocytosis & its mechanism.
7. Know the fate of acute inflammation.
 Introduction
• Inflammation is a response of vascularized tissues to infections
and damaged tissues that brings cells and molecules of host
defense from the circulation to the sites where they are needed,
in order to eliminate the offending agents.
• Protective response to rid the host of both the cause of injury (e.g.,
microbes, toxins) and the consequences of such injury (necrotic
cells & tissues).
• Without inflammation, infections would go unchecked, wounds
would never heal, and injured tissues might remain permanently.
 Types of Inflammation
• Acute inflammation:
a) Acute inflammation is a rapid, self-limited response to offending
agents that are readily eliminated, such as many bacteria and fungi &
dead cells.
b) If the offending stimulus is eliminated, the reaction subsides, and
residual injury is repaired.
• Chronic inflammation:
a) Inflammation of longer duration and is associated with more tissue
destruction and scarring (fibrosis).
b) May follow acute inflammation or arise de novo.
c) Usually as a response to agents that are difficult to eradicate.
 Comparison between acute & chronic
inflammation
Features Acute Inflammation Chronic Inflammation
Onset Fast: minutes to hours Slow: days
Cellular infiltrate Mainly neutrophil Monocyte/Macrophage,
lymphocyte
Tissue injury Usually mild & self limited Usually severe &
progressive
Fibrosis Absent Usually present
Local & systemic signs Prominent Less prominent
 Sequential steps of Inflammation
1. The offending agent located in extravascular tissues, is
recognized by host cells and molecules.
2. Leukocytes and plasma proteins are recruited from the
circulation to the site where the offending agent is located.
3. The leukocytes and proteins are activated and work together to
destroy and eliminate the offending substance.
4. The reaction is controlled and terminated.
5. The damaged tissue is repaired.
The steps of the inflammatory response can be remembered as the
five R’s:
1. recognition of the injurious agent.
2. recruitment of leukocytes.
3. removal of the agent.
4. regulation (control) of the response.
5. repair (resolution).
Macrophages and other cells in
tissues recognize microbes and
damaged cells and liberate
mediators, which trigger the
vascular and cellular reactions of
inflammation.

Fig: Sequence of events in an

inflammatory reaction.
 Causes of Inflammation
• Infections: Bacterial, viral, fungal, parasitic
• Tissue necrosis
• Foreign bodies: splinter, dirt, sutures
• Immune reactions (hypersensitivity)
 Diseases caused by Inflammation
Disorders Cells & molecules involved in injury
Acute Inflammation
Acute respiratory distress syndrome (ARDS) Neutrophils
Asthma Eosinophils, IgE antibodies
Glomerulonephritis Antibodies & complements; neutrophils &
monocytes
Septic shock Cytokines
Chronic Inflammation
Arthritis Lymphocytes, macrophages & antibodies?
Asthma Eosinophils, IgE antibodies
Atherosclerosis Macrophages, lymphocytes
Pulmonary fibrosis Macrophages, fibroblasts
 Recognition of Microbes and Damaged
Cells
• Recognition of microbial components or substances released from damaged
cells is the initiating step in inflammatory reactions.
• Several cellular receptors and circulating proteins are capable of recognizing
microbes and products of cell damage and triggering inflammation.
1. Cellular receptors for microbes: Toll like receptors (TLRs)
➢Expressed on epithelial cells, dendritic cells, macrophages, and other
leukocytes.
➢Acts by producing molecules like adhesion molecules on endothelial cells,
cytokines, and other mediators >> induces inflammation.
2. Sensors of cell damage: NOD like receptors (NLRs)
➢Uric acid, ATP, decreased intracellular, K++ ,DNA.
➢Acts my activating multiprotein complex inflammasome>> induces the
production of the cytokine IL-1 >> recruits leukocytes >> induces inflammation.
3. Other cellular receptors:
➢receptors for the Fc tails of antibodies and for complement proteins.
➢These receptors recognize microbes coated with antibodies and
complement (the coating process is called opsonization) and promote
ingestion and destruction of the microbes as well as inflammation.
4. Circulating proteins:
➢mannose binding lectin recognizes microbial sugars and promotes
ingestion of the microbes and the activation of the complement system.
➢Other proteins called collectins also bind to and combat microbes.
 Acute Inflammation
• Acute inflammation has three major components:
1. dilation of small vessels leading to an increase in blood flow.
2. increased permeability of the microvasculature enabling plasma
proteins and leukocytes to leave the circulation.
3. emigration of leukocytes from the microcirculation, their
accumulation in the focus of injury, and their activation to
eliminate the offending agent.
 Cardinal signs of acute inflammation
• The vascular and cellular reactions account for the cardinal signs of
inflammation: rubor, calor, tumor, dolor and functio laesa.
• The redness (rubor), warmth (calor), and swelling (tumor) are
caused by the increased blood flow and edema.
• Due to the damage and the liberation of prostaglandins,
neuropeptides, and cytokines, one of the local symptoms is pain
(dolor).
• Loss of function (functio laesa) results from pain and injury to the
tissues.
 Reaction of the blood vessels in acute
inflammation
• Changes in the blood flow & caliber.
• Permeability of the blood vessels (Vascular leakage).

This changes in the blood vessels causes movement of plasma

proteins and leukocytes out of the circulation and into the site of
infection or injury.
 Exudate & Transudate
• Exudate: an exudate is an extravascular fluid that has a high
protein concentration and contains cellular debris. Its presence
implies an underlying inflammatory process.
• Transudate: a transudate is a fluid with low protein content (most
of which is albumin), little or no cellular material, and low specific
gravity.
• Pus (purulent exudate): an inflammatory exudate rich in
leukocytes (mostly neutrophils), the debris of dead cells, and, in
many cases, microbes.
Mechanism of Exudate & Transudate
 Differences between Exudate &
Transudate
Criteria Exudate Transudate
Cause Inflammatory Non inflammatory
Mechanism Increased vascular Increased hydrostatic pressure
permeability & decreased oncotic pressure

Examples Pus CCF, hepatic failure, renal

failure
Appearance Hazy, cloudy Clear
Clot Present Absent
Protein High Low
Lactate dehydrogenase High Low
Specific gravity High Low
Cell count High low
Predominant cells Neutrophils & lymphocytes Lining cells
 Changes in the blood flow & caliber
• Vasodilation
• Increased permeability of the microvasculature
• Vascular stasis
• Accumulation of neutrophils along the vascular endothelium which
then migrate through the vascular wall into the interstitial space.
 Vasodilation
• Earliest manifestation of acute inflammation.
• Mediated by histamine.
• Involves in the arterioles & progressively involves new capillary
beds.
• Ultimately leads to increased blood flow to the site.
• Causes local heat (calor) & erythema (rubor).
 Vascular leakage (Increased Vascular
Permeability)
• Contraction of endothelial cells (immediate transient response):
1. Due to mediators like histamine, bradykinin & leukotrienes.
2. occurs rapidly after exposure to the mediator and is usually short-
lived (15 to 30 minutes).
3. May be delayed in some forms of injury ex- burn, irradiation,
exposure to certain toxins.
• Endothelial injury:
1. due to endothelial cell necrosis & detachment.
2. May be direct (thermal burns) or induced (microbes or microbial
toxins)
Fig: Mechanism of increased vascular permeability in acute inflammation.
Response of lymph vessels & lymph nodes
• Usually the lymph vessels drain out the small amount of extravascular
fluid that seeps out of capillaries.
• Acute inflammation causes increased vascular permeability causing
increased extravascular fluid.
• This extravasated fluid often contains microbes in addition to fluid,
leukocytes & cell debris.
• The lymphatics may become secondarily inflamed (lymphangitis), as
may the draining lymph nodes (lymphadenitis).
• The lymph nodes undergo hyperplasia of lymphoid follicles & become
enlarged (reactive lymphadenitis).
• Sometimes red streaks near a skin wound may be present (inflamed
lymphatic channels) which is a telltale sign of bacterial infection.
 Leukocytes recruitment to the site of
infection
• The changes in blood flow and vascular permeability are quickly
followed by an influx of leukocytes into the tissue.
• Their function is to eliminate the offending agents.
• The most important leukocytes are the ones capable of
phagocytosis, namely neutrophils (acute) and macrophages
(chronic).
• They ingest and destroy bacteria and other microbes, as well as
necrotic tissue and foreign substances.
• Macrophages also produce growth factors that aid in repair.
 Vascular Stasis
• Vasodilation & increased vascular permeability causes increased
vessel diameter & loss of vascular volume.
• Causes increased concentration of RBC which leads to increased
viscosity of the blood.
• These events ultimately causes vascular stasis.
 Recruitment of leukocytes in the site of
inflammation
• The journey of leukocytes from the vessel lumen to the tissue is a
multistep process that is mediated and controlled by adhesion
molecules and cytokines called chemokines.
• This process can be divided into sequential phases-
1. In the lumen:
➢Margination, rolling, and adhesion to endothelium.
➢In inflammation, the endothelium is activated and can bind
leukocytes which initiates their exit from blood vessels.
2. Migration across the endothelium and vessel wall.
3. Migration in the tissues toward a chemotactic stimulus.
 In the lumen
• Margination: dilation of inflamed post capillary venules & vascular
stasis causes the WBC to assume a more peripheral position along
the endothelial surface which is called margination.
• Rolling: movement of the WBC along the endothelium.
• Adhesion to the endothelium: mediated by two groups of
chemokines known as selectins & integrins.
 Selectins
• Initial rolling movement are mediated by selectins. These are of
three types-
a) L-selectin: expressed on leukocytes.
b) E-selectin: expressed on endothelium.
c) P-selectin: expressed on platelets.
• The expression of selectins and their ligands is regulated by
cytokines produced in response to infection and injury.
• The ligand for selectins are Sialyl-Lewis X expressed on various
cells.
 Different type of Selectins
Molecules Distribution Activated by Ligand Expressed on
L selectin Neutrophils, TNF, IL-1 Sialyl-Lewis X Endothelium
monocytes,
naïve T & B
cells
E-selectin Endothelium TNF, IL-1 Sialyl-Lewis X Neutrophils,
Monocytes, T cells
P- selectin Platelets & TNF, IL-1, Sialyl-Lewis X Neutrophil,
endothelium Histamine, Monocytes, T cells
thrombin
 Integrins
• The weak rolling interactions slow down the leukocytes and give them
the opportunity to bind more firmly to the endothelium. Firm adhesion
is mediated by a family of leukocyte surface proteins called integrins.
• TNF and IL-1 induce endothelial expression of ligands for integrins.
• Ligand for β 1 integrin VLA-4 is VCAM-1 (Vascular cell adhesion molecule-
1)
• Ligand for β 2 integrin LFA-1 & MAC-1 is ICAM-1 (Intercellular cell
adhesion molecule-1)
• After the firm adhesion the leukocytes stop rolling & they spread out on
the endothelial surface.
 Different type of Integrins
Types Distribution Ligands expressed on
endothelium
β 1 integrin VLA-4 Monocytes , T cells VCAM-1 (Vascular cell
adhesion molecule-1)
β 2 integrin LFA-1 Neutrophils, Monocytes , ICAM-1 (Intercellular
T cells cell adhesion
molecule-1)
β 2 integrin LFA-1 Monocytes , Dendritic ICAM-1 (Intercellular
cells cell adhesion
molecule-1)
Leukocyte migration through endothelium
• Migration of the leukocytes through intact endothelium is called
transmigration or diapedesis.
• Occurs mainly in post capillary venules.
• Chemokines act on the adherent leukocytes and stimulate the cells to
migrate through inter-endothelial gaps toward the chemical
concentration gradient.
• Several adhesion molecules present in the intercellular junctions
between endothelial cells are involved in the migration of leukocytes.
• Among these molecules CD31 or PECAM-1 (platelet endothelial cell
adhesion molecule) is the most prominent.
• After traversing the endothelium, leukocytes pierce the basement
membrane by secreting collagenases, and enter the extravascular
space.
• Thus the cells that have exited the vessel then migrate toward the
chemotactic gradient created by chemokines and other
chemoattractants and accumulate in the extravascular site.
Fig: Multistep process of leukocyte migration through blood vessels.
 Chemotaxis of leukocytes
• Movement of leukocytes in the tissues toward the site of injury
along a chemical gradient is defined as chemotaxis.
• These chemotactic agents may be exogenous & endogenous.
• Exogenous substances include bacterial products.
• Endogenous substances:
a) Cytokines: IL-8
b) Components of complement system: C5a
c) Arachidonic acid metabolites: Leukotriene B4
 Mechanism of Chemotaxis
Chemoattractant’s bind to G- protein coupled transmembrane
receptors on leukocytes

Activation of second messenger system

Polymerization of actin at the leading edge of the cells & localization

of myosin filaments at back of the cells

Formation of filopodia that extend the cell towards the site of

attraction
 Phagocytosis
• In the 1880s Russian biologist Elie Metchnikoff discovered the
process of phagocytosis.
• Phagocytosis involves three sequential steps-
1. Recognition and attachment of the particle to be ingested by the
leukocyte.
2. Engulfment, with subsequent formation of a phagocytic vacuole.
3. Killing of the microbe and degradation of the ingested material.
• The two major phagocytes are neutrophils and macrophages.
 Recognition & Attachment
• Recognition of microbes or dead cells induces several responses in
leukocytes that are collectively called leukocyte activation.
• Activation results from triggering of signaling pathways in
leukocytes, resulting in increases in cytosolic Ca2+ and activation of
enzymes such as protein kinase C and phospholipase A2.
• Mannose receptors, scavenger receptors, and receptors for
various opsonins enable phagocytes to bind and ingest microbes.
These are known as phagocytic receptors.
• Mannose receptor is a lectin that binds terminal mannose and
fucose residues of glycoproteins and glycolipids which are usually
present in microbial cell wall.
• Scavenger receptors bind to modified LDL particles.
• Several opsonins enhances the efficiency of phagocytosis.
• Major opsonins are IgG, C3b, mannose binding lectin & collectins.
 Engulfment
• After a particle is bound to phagocyte receptors, extensions of the
cytoplasm flow around it.
• The plasma membrane pinches off to form an intracellular vesicle
(phagosome) that encloses the particle.
• The phagosome then fuses with a lysosomal granule, which
discharges its contents into the phagolysosome.
• During this process the phagocyte may also release lysosome
contents into the extracellular space.
 Killing & Degradation of intracellular
microbes
• Killing of microbes is accomplished by reactive oxygen species
(ROS) and reactive nitrogen species (derived from nitric oxide) and
also lysosomal enzymes.
• The killing and degradation of microbes and dead cell debris within
neutrophils and macrophages occur most efficiently after
activation of the phagocytes.
• All these killing occurs in lysosomes where phagocytosed
materials are bought.
 Reactive Oxygen Species (ROS)
• ROS are produced by the activation of NADPH oxidase (also called
phagocyte oxidase), which oxidizes reduced nicotinamide-adenine
dinucleotide phosphate (NADPH) and, in the process, reduces
oxygen to superoxide anion (O2-)
• This oxidative reaction is triggered by activating signals
accompanying phagocytosis and is called the respiratory burst.
• O2- is converted into hydrogen peroxide (H2O2), mostly by
spontaneous dismutation.
• H2O2 is not able to efficiently kill microbes by itself.
• The azurophilic granules of neutrophils contain the enzyme
myeloperoxidase (MPO), which, in the presence of a halide (Cl−),
converts H2O2 to hypochlorite (HOCl-) which is a potent
antimicrobial agent that destroys microbes by halogenation or by
lipid peroxidation.
• The H2O2-MPO-Halide system is the most potent bactericidal
system of neutrophils.
• H2O2 is also converted to hydroxyl radical (OH-), another powerful
destructive agent.
 Reactive Nitrogen Species
• Derived from nitric oxide (NO).
• Nitric oxide (NO), a soluble gas produced from arginine by the
action of nitric oxide synthase (NOS).
• There are three different types of NOS:
a) endothelial (eNOS)
b) neuronal (nNOS)
c) inducible (iNOS)
• eNOS and nNOS are constitutively expressed at low levels, and the
NO they generate functions to maintain vascular tone and as a
neurotransmitter, respectively.
• iNOS, is involved in microbial killing, is induced when macrophages
& neutrophils are activated by cytokines (e.g., interferon-γ) or
microbial products.
• NO reacts with superoxide to generate the highly reactive free
radical peroxynitrite (ONOO−).
• These nitrogen-derived free radicals, similar to ROS, attack and
damage the lipids, proteins, and nucleic acids of microbes thereby
killing them.
 Lysosomal Enzymes & Proteins
• Neutrophils and macrophages contain lysosomal granules that
contribute to microbial killing and, when released, may cause tissue
damage.
• Neutrophils have two main types of granules-
• The smaller specific (or secondary) granules contain lysozyme,
collagenase, gelatinase, lactoferrin, plasminogen activator,
histaminase, and alkaline phosphatase.
• The larger azurophil (or primary) granules contain MPO,
bactericidal proteins (lysozyme, defensins), acid hydrolases, and a
variety of neutral proteases (elastase, cathepsin G, nonspecific
collagenases, proteinase 3)
• Both types of granules can fuse with phagocytic vacuoles
containing engulfed material or the granule contents can be
released into the extracellular space during frustrated
phagocytosis.
• Different granule enzymes serve different purposes-
1. Acid phosphatases degrade bacteria & debris.
2. Neutral proteases degrade extracellular components like
collagen, fibrin, elastin, cartilage, basement membrane.
3. Neutrophil elastases degrade virulence factors of bacteria.
Fig: Phagocytosis 1. Recognition & attachment 2. Engulfment
3. Killing & degradation
 Neutrophil Extracellular Trap (NET)
• Neutrophil extracellular traps (NETs) are extracellular fibrillar
networks that concentrate antimicrobial substances at sites of
infection and trap microbes, helping to prevent their spread.
• They are produced by neutrophils in response to infectious
pathogens (mainly bacteria and fungi) and inflammatory mediators
(e.g., chemokines, cytokines [mainly interferons], complement
proteins, and ROS).
 Mediators of Inflammation
• Inflammatory mediators are the substances that initiate and
regulate inflammatory reactions.
• The most important mediators of acute inflammation are
vasoactive amines, lipid products (prostaglandins and
leukotrienes), cytokines (including chemokines), and products of
complement activation.
• Mediators are either secreted by cells or generated from plasma
proteins.
 Mediators Source Actions
Histamine Mast cells, Basophils, Platelets Vasodilation, increased vascular permeability,
endothelial activation
Prostaglandin Mast cell, Leukocytes Vasodilation, pain, fever
Leukotrienes Mast cell, Leukocytes Increased vascular permeability, chemotaxis,
leukocyte adhesion and activation
Cytokines Macrophages, endothelial cells, Local: endothelial activation
mast cells Systemic: Fever, Hypotension
Chemokines Leukocytes, activated macrophages Chemotaxis, leukocyte activation

Platelet Leukocytes, mast cells Vasodilation, increased vascular permeability,

activating leukocyte adhesion, chemotaxis,
factor degranulation, oxidative burst
Complement Plasma (produced in liver) Leukocyte chemotaxis and activation, direct
target killing (membrane attack
complex), vasodilation (mast cell stimulation)
Kinins Plasma (produced in liver) Increased vascular permeability, smooth
muscle contraction, vasodilation, pain
 Vasoactive Amines
• The two major vasoactive amines are histamine and serotonin.
• The richest source of histamine is mast cell & also in basophils,
platelets.
• Histamine is released by mast cell degranulation in response to-
1. physical injury (such as trauma), cold, and heat.
2. binding of antigen to IgE antibodies displayed on the surfaces of
mast cells (immediate hypersensitivity reactions).
3. products of complement called anaphylatoxins (C3a and C5a)
4. Neuropeptides (Substance P) and cytokines (IL-1, IL-8) may also
trigger release of histamine.
 Serotonin
• Serotonin (5-hydroxytryptamine) is a preformed vasoactive
mediator present in platelets and certain neuroendocrine cells,
such as in the gastrointestinal tract.
• Its primary function is as a neurotransmitter in the gastrointestinal
tract and the central nervous system.
• It is also a vasoconstrictor, but the importance of this action in
inflammation is unclear.
 Arachidonic Acid Metabolites
• Prostaglandins and leukotrienes are produced from arachidonic
acid (AA) present in membrane phospholipids and stimulate
vascular and cellular reactions in acute inflammation.
• Mechanical, chemical, and physical stimuli or other mediators (e.g.,
C5a) release AA from membrane phospholipids through the action
of cellular phospholipases (phospholipase A2).
• By the action of cyclooxygenase, prostaglandins, prostacyclins &
Thromboxane A2 are derived.
• By the action of lipoxygenease, leukotrienes & lipoxins are derived.
 Fig: Mediators of acute
inflammation (Arachidonic Acid
derivatives)
 Action of AA metabolites
Action AA metabolites
Vasodilation PGI2 (Prostacyclin), PGE1, PGE2,
PGD2
Vasoconstriction Thromboxane A2, Leukotrienes
C4, D4, E4
Increased vascular permeability Leukotrienes C4, D4, E4
Chemotaxis, leukocyte adhesion Leukotrienes B4
 Cytokines
• Cytokines are proteins produced by many cell types that mediate
and regulate immune and inflammatory reactions.
• These cells include activated lymphocytes, macrophages, and
dendritic cells, but also endothelial, epithelial, and connective
tissue cells.
 Cytokines in Acute Inflammation
Cytokines Principal source Principal action
TNF Macrophage, Mast cell, T Expression of endothelial
lymphocytes adhesion molecules and
secretion of other cytokines;
systemic effects
IL-1 Macrophage, Endothelial cell, Similar to TNF
Epithelial cell
IL-6 Macrophage, other cells Systemic effects
Chemokines Macrophages, endothelial cells, Recruitments of leukocytes to
mast cells, T lymphocytes, acute inflammation
IL-17 T lymphocytes Recruitment of neutrophils &
monocytes
 Cytokines in Chronic Inflammation
Cytokines Principal source Principal action
IL-12 Dendritic cells, Increased production of IFN-γ
Macrophages
IFN-γ T lymphocytes, NK cells Activation of macrophages
IL-17 T lymphocytes Recruitment of neutrophils &
monocytes
 TNF & IL-1
• Mediates leukocyte recruitment by promoting adhesion of
leukocytes to endothelium and their migration through blood
vessels.
• Mainly produced by activated macrophages & dendritic cells.
• Main function:
1. Endothelial activation.
2. Activation of leukocytes & other cells.
3. Systemic acute phase response.
Fig: Major role of cytokines in acute inflammation
 Chemokines
• Chemokines are a family of small (8 to 10 kDa) proteins that act
primarily as chemoattractants for specific types of leukocytes.
• They are classified into four major groups, according to the
arrangement of cysteine (C) residues in the proteins.
1. C-X-C chemokines
2. C-C chemokines
3. C chemokines
4. CX3C chemokines
 Functions of chemokines
• In acute inflammation:
1. Stimulate leukocyte attachment to endothelium.
2. Mediates chemotaxis.
• Maintenance of tissue architecture (homeostatic chemokines)
 Complement system
• The complement system is a collection of plasma proteins that
function mainly in host defense against microbes and in pathologic
inflammatory reactions.
• The system consists of more than 20 proteins, some of which are
numbered C1 through C9.
• Complement proteins are present in inactive forms in the plasma,
and many of them are activated to become proteolytic enzymes
that degrade other complement proteins, thus forming an
enzymatic cascade capable of tremendous amplification.
 Pathways of complement activation
• The Classic pathway: triggered by binding of C1 to antibody (IgM or IgG)
that has combined with antigen.
• The Alternate pathway: triggered by microbial surface molecules (e.g.,
endotoxin, or lipopolysaccharide), complex polysaccharides, in the
absence of antibody.
• The Lectin pathway: plasma mannose-binding lectin binds to
carbohydrates on microbes and directly activates C1.

All three pathways of complement activation lead to the formation of an

active enzyme called C3 convertase, which splits C3 into two functionally
distinct fragments, C3a and C3b.
Fig: Pathways of complement activation & their functions
 Functions of complement system
1. Inflammation: C5a, C3a
2. Opsonization & phagocytosis: C3b
3. Cell lysis: Membrane attack complex (MAC) by C5b,C6,C7,C8,C9
 Principal mediators in different reactions
of inflammation
Reaction of inflammation Principal mediators
Vasodilation Histamine, Prostaglandins
Increased vascular permeability Histamine, Serotonin, C3a, C5a,
LTC4, D4, E4
Chemotaxis, leukocyte recruitment TNF, IL-1, Chemokines,C3a, C5a,
& activation Leukotriene B4
Fever IL-1, TNF, Prostaglandins
Pain Prostaglandins, Bradykinin, Substance P
Tissue damage Lysosomal enzymes of leukocytes,
Reactive oxygen species
 Morphologic patterns of acute
inflammation
• The morphologic hallmarks of acute inflammatory reactions are
dilation of small blood vessels and accumulation of leukocytes and
fluid in the extravascular tissue.
• Some specific morphologic patterns are seen in specific conditions.
These are-
1. Serous inflammation
2. Fibrinous inflammation
3. Purulent inflammation & abscess
4. Ulcers
 Serous inflammation
• Serous inflammation is marked by the exudation of cell poor fluid
into spaces created by cell injury or into body cavities.
• Usually devoid of any microbes.
• Usually due to increased vascular permeability or local irritation.
• The skin blisters in burns represents accumulation of serous fluid
below the damaged skin.
 Fibrinous inflammation
• A fibrinous exudate develops when the vascular leaks are large or
there is a local procoagulant stimulus (e.g., caused by cancer cells).
• With greater increase in vascular permeability, large molecules
such as fibrinogen pass out of the blood, and fibrin is formed and
deposited in the extracellular space.
• This fibrin can be dissolved by fibrinolysis or removed by
macrophages.
• If the fibrin is not removed fibroblast ingrowth can occur which
may lead to fibrosis or scarring (fibrinous pericarditis).
 Purulent inflammation & Abscess
• Purulent inflammation is characterized by the production of pus, an
exudate consisting of neutrophils, the liquefied debris of necrotic cells
and edema fluid.
• The most frequent cause of purulent (also called suppurative)
inflammation is infection with bacteria that cause liquefactive tissue
necrosis (pyogenic bacteria e.g. Staphylococci)
• Abscesses are localized collections of pus caused by suppuration buried
in a tissue, an organ, or a confined space.
• Abscesses have a central liquefied region composed of necrotic
leukocytes and tissue cell, then a zone of neutrophils, then a zone of
parenchymal or fibroblastic proliferation indicating chronic inflammation
& repair.
 Ulcers
• An ulcer is a local defect, or excavation, of the surface of an organ or tissue
that is produced by the sloughing (shedding) of inflamed necrotic tissue.
• Ulceration can occur only when tissue necrosis and resultant inflammation
exist on or near a surface.
• Common sites are-
1. mucosa of the mouth, stomach, intestines, or genitourinary tract.
2. skin and subcutaneous tissue of the lower extremities in individuals with
disorders that predispose to vascular insufficiency.
• In acute stage: intense polymorphonuclear infiltration and vascular dilation.
• In chronic stage: fibroblastic proliferation, scarring & accumulation of
lymphocytes, macrophages, and plasma cells.
 Outcomes of Acute inflammation
• Complete resolution.
• Healing by connective tissue replacement (scarring or fibrosis).
• Progression of the response to chronic inflammation.
Fig: Outcomes of acute inflammation.
Thank You!!!