1. Inflammation. Etiology.
Vascular changes. Cellular
events in inflammation.
Acute inflammation.
Morphologic patterns.

2. Questions
 Inflammation. Definition. Basis. Etiology
and pathogenesis. Nomenclature.
 Acute inflammation: tissue response.
Mediators in acute inflammation.
 Type of cells in the focus of acute
inflammation. Consequences of acute
inflammation.
 Patterns of acute inflammation.

3. Inflammation
 A protective response intended to eliminate
the initial cause of cell injury as well as the
necrotic cells and tissues resulting from the
original insult.
 Inflammation is a beneficial host response
to foreign invaders and necrotic tissue, but it
is itself capable of causing tissue damage.

4. General Features of Inflammation
 The main components of inflammation are a
vascular reaction and a cellular response, activated
by mediators that are derived from plasma proteins
and various cells.
 The phases of the inflammatory process are:
 Tissue injury, degeneration and necrosis
 Acute inflammation
 Inactivation and removal of the agent

Restitutio (repair)

Scar /chronic inflammation

5. Inflammation
 Acute inflammation
 rapid in onset and of short duration, lasting up to few
days
 characterized by fluid and plasma protein exudation and
 predominantly neutrophilic leukocyte accumulation

= exudative inflammation
 Chronic inflammation
 longer duration (days to years)
 characterized by lymphocytes and macrophages influx
and vascular proliferation and fibrosis (scarring)

= productive inflammation

6. Acute inflammation
 The external manifestations of
inflammation, often called its cardinal signs,
result from the vascular changes and cell
recruitment:
 heat (calor),
 redness (rubor),
 and swelling (tumor).
 pain (dolor)
 and loss of function (functio laesa)

7. Causes of acute inflammation
 Microbial infections
 pyogenic bacteria, viruses
 Hypersensitivity reactions
 parasites, tubercle bacilli
 Physical agents
 trauma, ionising radiation, heat, cold
 Chemicals
 corrosives, acids, alkalis, reducing agents,
bacterial toxins
 Tissue necrosis
 ischaemic infarction

8. Inflammation /Nomenclature
 Related to organ localization + itis

Pleura –pleuritis

Myocardium – myocarditis

Cystis – cystitis
 Exceptions

Pneumonia, angina

9. ACUTE INFLAMMATION
 Acute inflammation is a rapid
response to injury or microbes
and other foreign substances
that is designed to deliver
leukocytes and plasma proteins
to sites of injury.
 The principal leukocytes in
acute inflammation are
neutrophils (polymorphonuclear
leukocytes).
Granulocytes,
Neutrophilic
granulocytes
Polymorph

10. Role of the neutrophil polymorph
 The neutrophil polymorphs =
acute inflammatory infiltrate
 Movement
 Adhesion to micro-organisms
 Phagocytosis
 Intracellular killing of micro-
organisms

Oxygen-dependent mechanisms –
RAS

Oxygen-independent mechanisms

11. ACUTE INFLAMMATION
 Acute inflammation has 3 major
components:
 Vascular changes:

alterations in vessel caliber resulting
in increased blood flow (vasodilation)
and (increased vascular permeability).
 Cellular events:

emigration of the leukocytes from the
microcirculation and accumulation in
the focus of injury (cellular recruitment
and activation).
 Mediators, derived from plasma
proteins and cells

12. Vascular Reactions in Acute
Inflammation
 Vasoconstriction (for seconds)
 Vasodilation is induced by chemical mediators
such as histamine
 is the cause of erythema and stasis of blood flow.
 Increased vascular permeability
 by histamine, kinins and other mediators that produce
gaps between endothelial cells,
 by direct or leukocyte-induced endothelial injury, and
 by increased passage of fluids through the endothelium

13. Exudates
 Exudates
 increased vascular permeability allows
plasma proteins and leukocytes to enter
sites of infection or tissue damage;
 fluid leak through blood vessels results in
edema.
 Exudates v/s transudates
 Exudate - in inflammation because of
increased vascular permeability as a
result of increased interendothelial
spaces.
 Transudates - when fluid leaks out
because of increased hydrostatic
pressure or decreased osmotic pressure.

14. Responses of Lymphatic Vessels
 In inflammation, lymph flow is increased and helps
drain edema fluid from the extravascular space
 In severe inflammatory reactions, especially to
microbes, the lymphatics may transport the
offending agent.
 lymphangitis and lymphadenitis

Inflamed lymph nodes are often enlarged, because of
hyperplasia of the lymphoid follicles and increased numbers of
lymphocytes and phagocytic cells lining the sinuses of the lymph
nodes = reactive, or inflammatory, lymphadenitis.

For clinicians, the presence of red streaks near a skin wound is a
sign of an infection in the wound.

15. Cellular Events
 Leukocyte Recruitment
 Leukocytes are recruited from the blood into the
extravascular tissue to the site of infection or tissue injury,
and are activated.
 Leukocyte Activation- to perform their functions
 ingest offending agents, kill bacteria and other microbes,
and eliminate necrotic tissue and foreign substances.
 they may induce tissue damage and prolong inflammation,
since the leukocyte products that destroy microbes can
also injure normal host tissues.

key to the normal function of leukocytes in host defense is to
ensure that they are recruited and activated only when needed

16. Leukocyte Recruitment – a multiple steps
process
 Margination, adhesion, and rolling along the vessel wall
 Firm adhesion to the endothelium
 Transmigration between endothelial cells;
 Migration in interstitial tissues toward a chemotactic stimulus
 mediated by the binding of complementary adhesion molecules on
leukocytes and endothelial surfaces – selectins, integrins
 Chemical mediators-chemoattractants

17. Leukocyte Activation
 Stimuli for activation
 microbes, products of necrotic cells, and several
mediators

opsonization
 components of the microbes and dead cells, or host proteins,
(opsonins), that coat microbes and target them for
phagocytosis

Leu express on their surface different kinds of receptors
 receptors for opsonins that facilitate rapid phagocytosis of the
coated microbes

Fc receptor for IgG, complement receptors 1 and 3, and
C1q (collectins).

18. Leukocyte Activation
 Stimuli for activation
 microbes, products of necrotic cells, and several
mediators

Leu express on their surface different kinds of receptors and
engagement of these receptors by microbial products or by
various mediators of inflammation induces leukocyte activation
 Leukocyte functions:
 Phagocytosis of particles

an early step in the elimination of harmful substances.
 Production of substances that destroy phagocytosed
microbes and remove dead tissues

lysosomal enzymes and reactive oxygen and nitrogen species.
 Production of mediators that amplify the inflammatory
reaction- arachidonic acid metabolites, cytokines.

19. Leukocyte Effector Mechanisms
 The culmination of the phagocytosis of
microbes is killing and degradation of the
ingested particles.
 Destruction is caused by free radicals (ROS, NO)
and lysosomal enzymes

leukocyte NADPH oxidase (phagocyte oxidase) -
superoxide ion and hydrogen peroxide

lysosomes of neutrophils (called azurophilic granules)
-enzyme myeloperoxidase (MPO) - hypochlorous
radical.
 Enzymes and ROS may damage normal tissues

20. CHEMICAL MEDIATORS OF
INFLAMMATION
 Cell-derived mediators - produced locally by cells at the
site of inflammation
 In intracellular granules and are rapidly secreted upon cellular activation
(e.g., histamine in mast cells) or are synthesized de novo in response to
a stimulus (e.g., prostaglandins and cytokines).
 Plasma-protein-derived mediators- circulating in the
plasma (typically synthesized by the liver) as inactive
precursors that are activated at the site of inflammation
 complement proteins, kinins, which undergo proteolytic cleavage to
acquire their biologic activities.
 Once activated and released from the cell, mediators are
inactivated by enzymes, eliminated or inhibited

21. The principal chemical mediators
of inflammation

22. The Actions of the Principal Mediators of
Inflammation

23. Major Cell-derived Mediators of
Inflammation
 Vasoactive amines -histamine, serotonin
 main effects vasodilation and increased vascular permeability
 Arachidonic acid metabolites -prostaglandins and leukotrienes-derived
from cell membrane phospholipids
 involved in vascular reactions, leukocyte chemotaxis, and other reactions of
inflammation; antagonized by lipoxins
 Cytokines -proteins produced by many cell types (TNF, IL-1, chemokines)
 mediate multiple effects -leukocyte recruitment and migration;
 Reactive oxygen species (O2, superoxide, H2O2, peroxide, OH-,
hydroxyl
radical)-released from neutrophils and macrophages
 role in microbial killing, tissue injury
 Nitric oxide
 vasodilation, microbial killing
 Lysosomal enzymes –myeloperoxidase, lysozyme (bact.), acid
hydrolases, lactoferrin, lysozyme, alkaline phosphatase, proteases –
collagenase, elastases
 neutrophils and monocytes
 role in microbial killing, tissue injury

24. HISTAMINE
 Mast Cells, basophils
 Powerful vasodilatator
 Vasoactive “amine”
 inceases vascular
permeability

25. SEROTONIN
 5HT, 5-Hydroxy-
Tryptamine)
 Platelets and
Enterochromaffin Cells
 Vasoactive mediator, with
effects similar to those of
histamine
 Evokes NO synthetase

26. Arachidonic Acid (AA) Metabolites
(EICOSANOIDS)
 Affect a variety of biologic processes, including
inflammation and hemostasis.
 Leukocytes, mast cells, endothelial cells, and platelets are the
major sources of AA metabolites in inflammation.
 = Products derived from the metabolism of AA
 AA is a 20-carbon polyunsaturated fatty acid, a component
of cell membrane phospholipids.
 It is released from these phospholipids via cellular phospholipases,
activated by mechanical, chemical, or physical stimuli, or by
inflammatory mediators (C5a).
 AA metabolism - 2 enzymatic pathways:
 Cyclooxygenase ⇒ prostaglandins and thromboxanes,
 lipoxygenase ⇒ leukotrienes and lipoxins

27. Metabolites
(EICOSANOIDS)
 Effects
 Prostaglandins, thromboxanes

Pain, fever, clotting
 Leukotrienes

Chemotaxis, vasoconstriction, increased
Permeability
 Lipoxins

Inhibit chemotaxis, vasodilatation, counteract
actions of leukotrienes

28. Platelet-Activating Factor (PAF)
 It is generated from the membrane
phospholipids of many cells
• neutrophils, monocytes, basophils,
endothelial cells, and platelets
 Activate platelets
 Vasoconstriction and
bronchoconstriction
 Vasodilation and increased
vascular permeability

29. CYTOKINES/CHEMOKINES
 Proteins produced by many cells –
TNFα, IL-1,interferon-γ (IFN-γ)
 Lymphocytes, macrophages.
 Numerous roles in acute and
chronic inflammation
 CHEMOKINES are small proteins
(>40)
 act primarily as chemoattractants for
different subsets of leukocytes

30. FREE RADICALS
 Synthesized via the NADPH oxidase (phagocyte
oxidase) pathway and are released from neutrophils
and macrophages
 O2 – (SUPEROXIDE)
 H2O2 (PEROXIDE)
 OH-
(HYDROXYL RADICAL)
 Very destructive
 within lysosomes they function to destroy phagocytosed microbes and
necrotic cells
 At higher levels -responsible for tissue injury

31. NITRIC OXIDE
 Synthesized from arginine
 by endothelial cells (type III
nitric oxide synthase, eNOS)
 by macrophages (type II NO
synthase,iNOS)
 Effects
 Vasodilation
 reduces platelet and
leukocyte adhesion
 NO produced in phagocytes is
cytotoxic to microbes.

32. Lysosomal enzymes
 The lysosomal granules of neutrophils and
monocytes contain many molecules that can
mediate acute inflammation.
 Myeloperoxidase
 Lysozyme (Bact.)
 Acid Hydrolases
 Lactoferrin
 Lysozyme
 Alkaline Phosphatase
 Proteases – collagenase, elastases
 The potentially damaging effects of lysosomal
enzymes are checked by antiproteases present in
the serum and tissue fluids-α1-antitrypsin, α2-
macroglobulin.

33. Plasma Protein-Derived
Mediators of Inflammation
 Complement proteins, >20 proteins
 Coagulation proteins
 Activated factor XII triggers the clotting, kinin and
complement cascades, and activates the fibrinolytic
system, production of fibrin
 Kinins (bradykinin)
 Produced by proteolytic cleavage of precursors;
 increased permeability, Smooth muscle contraction
(non vascular), pain

34. COMPLEMENT SYSTEM
 >20 components, in circulating plasma
 Plays an important role in host defense
(immunity) and inflammation
 Upon activation, different
complement proteins coat
(opsonize) particles, such as
microbes, for phagocytosis and
destruction
 increase vascular permeability -
C3a and C5a
 leukocyte chemotaxis
 lysis of cell membranes, after an
extensive “cascade”

35. Outcomes of acute
inflammation
 Resolution,
 Healing by scarring
(fibrosis),
 Chronic
inflammation

36. Outcomes of acute
inflammation
 Resolution of inflammation
 when the injury is limited or short-lived and
there has been no or minimal tissue damage,
 when the tissue is capable of replacing any
irreversibly injured cells
 Termination of the acute inflammatory
response involves:

neutralization, decay or enzymatic degradation
of the various chemical mediators, normalization
of vascular permeability, cessation of leukocyte
emigration, death (by apoptosis) of extravasated
neutrophils.
 leukocytes produce mediators that inhibit
inflammation and thus limit the reaction
 lymphatic drainage and macrophage ingestion of
necrotic debris lead to the clearance of the
edema fluid, inflammatory cells, and detritus

37. Outcomes of Acute Inflammation
 Progression to chronic inflammation - if the
offending agent is not removed
 In some instances, signs of chronic inflammation may be
present at the onset of injury (e.g., in viral infections or
immune responses to self-antigens).
 Scarring or fibrosis - after substantial tissue
destruction or when inflammation occurs in tissues
that do not regenerate.
 Extensive fibrinous exudates may not be completely
absorbed and are organized by ingrowth of connective
tissue, with resultant fibrosis.
 The usual outcome of abscess formation is scarring
because of the underlying tissue destruction

38. ACUTE INFLAMMATION-
Summary
 Initial reaction of tissue to injury
 Vascular component: dilatation of vessels
 Exudative component: vascular leakage of
protein-rich fluid
 Neutrophil polymorph -the characteristic cell
recruited to the tissue
 Outcome - resolution, suppuration (e.g.
abscess), organisation, or progression to
chronic inflammation

39. Morphologic patterns of
acute inflammation

40. MORPHOLOGIC PATTERNS OF
ACUTE INFLAMMATION
 Distinctive morphologic patterns depend on:
 the severity of the inflammatory response, its specific
cause and the particular tissue

Serous inflammation

Catarrhal inflammation

Fibrinous inflammation

Haemorrhagic inflammation

Suppurative (purulent) inflammation

Putrefactive (gangrenous) inflammation
 Importance to know the morphologic patterns
 often associated with different eliciting stimuli and clinical
situations.

41. Serous inflammation
 Characterized by the outpouring of a watery,
relatively protein and cells-poor fluid
 Depending on the site of injury, the fluid derives either
from the serum or from the secretions of mesothelial
cells lining the peritoneal, pleural, and pericardial
cavities.
 Location
 Skin - viruses
 Mesothelial linings (serosa) of peritoneal, pleural, and
pericardial cavities

Fluid in a serous cavity is called an effusion
 Mucosa of GIT, respiratory tract (rhinitis)

Catarrhal inflammation – mucous + epithelial cells
 Liver, myocardium

42. Serous inflammation
 Skin blister -from a burn or viral
infection
 a serous effusion accumulated
either within or immediately
beneath the epidermis of the skin
 Outcome of serous
inflammation
 Recovery
 Exceptions

Serous meningitis

Cholera - dehydratation

burns

43. Fibrinous inflammation
 Occurs as a consequence of more severe
injuries, resulting in greater vascular
permeability and the exudate is rich of
fibrinogen⇒ converts to fibrin
 Location
 Serous cavities

Pericarditis, pleuritis, peritonitis
 Mucosa of respiratory tract

Diphtheria of the larynx

Lobar pneumonia –alveoli
 Mucosa of gastrointestinal tract
 Histologically, the accumulated extravascular
fibrin appears as an eosinophilic meshwork of
threads
 Cor villosum
 Weigert staining– violet-blue reaction

44. Fibrinous inflammation
 Two types
 Superficial – easy removing of fibrin, without
loss of tissue

Serous cavities

Lobar pneumonia (crupousa)

Diphtheria of larynx
 Deep –pseudomembraneous, necrosis of sub
lying epithelium

Diphtheria of tonsils

C. difficile

45. Pneumonia crouposa

46. Pericarditis fibrinosa

47. Pleuritis fibrinosa

48. Outcome of fibrinous inflammation
 Resolution
 exudates may be degraded by fibrinolysis, and the accumulated
debris may be removed by macrophages, resulting in restoration of
the normal tissue structure
 Organization
 the failure to completely remove the fibrin results in the ingrowth of
fibroblasts and blood vessels, leading ultimately to scarring that may
have significant clinical consequences

organization of a fibrinous pericardial exudate forms dense fibrous scar
tissue that bridges or obliterates the pericardial space and restricts
myocardial function

Pneumonia crouposa – carnification, pneumosclerosis
 Death
 Diphtheria of larynx – asphyxia
 Intoxication – peritonitis, pneumonia crouposa

49. Suppurative (purulent) inflammation
 Characterized by the presence of large amounts of purulent
exudate (pus) consisting of neutrophils, macrophages, necrotic
cells, and edema fluid
 Yellowish colour to grey
 Staphylococci induce most often suppuration = pyogenic.
 Two types
 Local (focal collections of pus) – abscesses

Directly, by seeding of pyogenic organisms into a tissue
 hair follicle - fulunculus, carbunculus
 Ductullar way - bronchi, bile ducts
 Hemaetogenic- several organs

by secondary infections (suppuration)
 Diffuse – phlegmone

No localization of the suppuration, neutrophils + tissue decay
 Adipose tissue-panniculitis
 Empyema – in cavities

Gall bladder, pleura

50. Bronchopneumonia
Purulent inflammation. A, Multiple bacterial abscesses in the lung B. The abscess
contains neutrophils and cellular debris, and is surrounded by congested blood
vessels.

51. Pneumonia lobularis

52. Nephritis purulenta

53. Leptomeningitis purulenta

54. Suppurative (purulent) inflammation
Chronic abscess
 Morphology
 a central, largely necrotic
region rimmed by a layer of
neutrophils, with a
surrounding zone of dilated
vessels and fibroblastic
proliferation
 may become completely
walled off and replaced by
pyogenic membrane, 4 layers

Neutrophils

Macrophages-lipids,
pseudoxantomas cells

Lymphocytes

connective tissue capsule
Abscessus cerebri

55. Outcome of suppurative inflammation
 Local factors
 Bile stasis,
 lithiasis
 General condition of the patient
 immunity
 diabetes
 Local effects
 Break in the cavities

Suppurative peritonitis
 Systemic effects-generalization of the inflammation
 Sepsis

Pyaemia-multiple abscesses

56. Haemorrhagic inflammation
 Characterized by increased erythodiapedesis due to
vascular wall injury
 Often combined fibrinohaemorrhagic
 Vasotropic agents- viruses
 Grippe – rhinitis, tracheitis, pharyngitis
 hemorrhagic fever
 Pestis
 Anthrax
 Impaired coagulation
 Thrombocytopenia
 ↓ Vit C

57. Ulcerative inflammation
 An ulcer is a local defect (or
excavation), of the surface of an organ
or tissue -necrotic tissue
 Ulceration can occur only when tissue
necrosis and inflammation exist on or
near a surface:
 inflammatory necrosis of the mucosa of
the mouth, stomach, intestines, or
genitourinary tract;
 tissue necrosis and subcutaneous
inflammation of the lower extremities
 Peptic ulcer of the stomach, duodenum -
acute and chronic inflammation coexist.
 acute stage - intense polymorphonuclear
infiltration and vascular dilation in the
margins of the defect.
 Chronic stage - the margins and base of
the ulcer develop scarring with
accumulation of lymphocytes,
macrophages, and plasma cells.