This document discusses inflammation. It defines inflammation as the protective host response to rid the body of stimuli, damaged tissues, and foreign antigens. It occurs in vascularized tissues and leads to fluid and leukocyte accumulation. The document outlines the different types of acute and chronic inflammation and their characteristics. It also describes the cardinal signs of inflammation and discusses the vascular, cellular, and chemical events that occur during acute inflammation, including chemotaxis, phagocytosis, and the roles of various chemical mediators. The outcomes of acute inflammation and features of chronic inflammation are also summarized.

1. Inflammation
Dr E Malyangu

2. 2
Inflammation
• Protective host response to rid body of stimuli,
damaged or necrotic tissues and foreign
antigen
• Occurs in vascularized tissue against stimuli
leading to accumulation of fluid and
leukocytes
• Protective – rids body of injurious stimulus
• Serves to destroy, dilute or wall off injurious
agent and sets in motion process of repair
• During repair injured tissue is replaced by
regeneration of cells or fibrous tissue, or both
• May be harmful in some situations - eg
hypersensitivity reaction

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Types of inflammation
• Acute – short duration, lasting minutes, hours
or days
- characterized by exudation of fluid and
plasma proteins
- emigration of leukocytes mainly neutrophils
• Chronic – longer duration
- associated with presence of lymphocytes &
macrophages
- proliferation of blood vessels, fibrosis and
tissue necrosis

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Cardinal signs of inflammation
• Rubor – redness
• Tumor – swelling
• Calor – heat
• Dolor – pain
• Functio laesa – loss of function

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Acute inflammation
• Immediate and early response to injurious
agent
• Three major components:
- alteration in vascular calibreblood flow
- structural changes in microvasculature –
plasma proteins and leukocytes leave
circulation
- emigration of leukocytes to focus of injury

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Vascular changes
• Changes in vascular flow and calibre occur early
• Transient vasoconstriction then vasodilatation
blood flow (heat and redness)
• Slowing of circulation due to permeability
exudation of fluid, blood viscosity and stasis
• Peripheral orientation of leukocytes along
endothelium (margination), followed by rolling and
migration into interstitium

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Vascular changes
• permeability exudation of protein-rich fluid into
interstitium intravascular osmotic pressure
oedema (swelling)
• permeability is due to:
- formation of endothelial gaps
- cytoskeletal reorganisationendothelial retraction
- direct endothelial injury causing cell necrosis
- leakage from new blood vessels

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Cellular events
• Movement of leukocytes to site of injury which then:
- ingest offending agents
- kill bacteria and other microorganisms
- degrade necrotic tissue and foreign antigens
- may prolong inflamm and induce tissue damage by
release of enzymes, chem mediators
• Leukocytes move to site of injury from lumen by:
- transmigration across endothelium (diapedesis)
- migration in interstitium towards chemotactic
stimulus
• In inflammatory lesion, neutrophils present in first 6 -
24 hours, monocytes in next 24 – 48 hrs

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Chemotaxis
Movt of leukocytes along chemical gradient due
to chemoattractants
• Exogenous agents:
- bacterial products
• Endogenous products:
- components of complement system eg C5a
- products of lipooxygenase pathway –
lekotrienes
- cytokines eg IL-8

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Phagocytosis
Three steps in phagocytosis:
• Recognition and attachment of particle
• Opsonisation – particle is coated to phagocytosis
• Engulfment –extension of cytoplasm (pseudopods)
around object
• Killing or degradation –superoxide is generated and
converted to H2O2
• Granules of neutrophils contain enzymes
• O2 independent mechanisms include bactericidal
permeability increasing protein, lysozyme,
lactoferrin, major basic protein

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Chemical mediators of inflammation
• Chemical compounds that modify or amplify
inflammatory process
• Originate from plasma or from cells
• Bind to specific receptors on target cells
• Can act on one or a few target cells
• Most are short-lived once activated
• Have potential to cause harmful effects

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1. Vasoactive amines (histamine and serotonin)
• Histamine derived from mast cells, basophils,
platelets in preformed state
• Causes dilatation of arterioles and permeability
• Serotonin (5-hydroxytryptamine) present in platelets
and enterochromaffin cells
• Actions similar to histamine
• Amines are released after platelets are stimulated
after contact with collagen, thrombin, ADP and Ab-
Ag complexes

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2. Plasma proteases
• Complement system
- after activation causes lysis by membrane attack complex.
Gives out components:
- C3a, C5a (anaphylatoxins) -permeability and vasodilation
- C5a –chemotactic agent, C3a –opsonin
• Kinin system
- results in generation of bradykinin
- permeability, causes contraction of smooth muscle, dilatation
of vessels, pain when injected into skin
- triggered by activation of FXII of intrinsic clotting pathway
• Clotting system – activation results in formation of
fibrinopeptides which permeability

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3. Arachdonic acid (AA) metabolites
• AA derived from diet or by conversion from linoleic
acid of cell membrane phospholipids
• AA by cycloxygenase pathway produces
prostaglandins (PG):
- thromboxane (TXA2) –vasoconstrictor and PLT
aggregating factor
- prostacyclin (PGI2) –vasodilator, inhibits PLT
aggregation
- PGD2, PGE2, PGF2 -cause vasodilation, potentiate
oedema

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AA metabolites
• Lipoxygenase pathway generates 5-HETE
leukotrines (LTs)
- 5-HETE –chemotactic agent
- LTB4 –chemotactic agent
- LTC4, LTD4, LTE4 –vasoconstriction,
bronchospasm, permeability
• Lipoxins
- inhibitors of inflammation
- inhibit leukocyte recruitment

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4. Platelet-activating factor (PAF)
• Derived from phospholipids in a number of cells
- causes PLT activation
- vasoconstriction and bronchoconstriction
- increases leukocyte adhesion to endothelium
• 5. Cytokines
–substances that modulate function of other cells
- include monokines, lymphokines, colony stim factors,
interleukins, chemokines, growth factors
- IL-1, TNF –fever, sleep, PGI synthesis
- chemokines – activate specific leukocytes and are
chemoattractants

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6. Nitric oxide (NO)
• Produced by endothelial cells, macrophages,
neurones
• Acts in a paracrine manner through cGMP
• Potent vasodilator
• Causes smooth muscle relaxation
• Reduces PLT aggregation and adhesion

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Outcomes of acute inflammation
• Complete resolution
• Abscess formation – infection by pyogenic
organisms
• Healing by connective tissue replacement
(fibrosis)
• Progression to chronic inflammation

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Chronic inflammation
• Inflammation of long duration
• There is active inflammation, tissue
destruction and attempts at repair at same time
• May follow acut inflm or may start from outset
as slow-grade smoldering response
• May arise under following conditions:
- persistent infection by organisms of low
toxicity that elicit delayed hypersensitivity rxn
eg fungi
- exposure to toxic or non-degradable agents
eg silica
- autoimmunity

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Histologic features
• Chronic inflammation characterised by:
- infiltration by mononuclear cells –
macrophages, lymphocytes, plasma cells
- tissue destruction
- healing by connective tissue replacement
which may result in fibrosis

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Cells in chronic inflammation
• Macrophages –derived from blood monocytes, liver
(Kupffer cells), spleen+LNs (sinus histiocytes), lungs
(alveolar macrophages)
• Lymphocytes –when activated produce lymphokines
and other substances
• Plasma cells – produce antibodies
• Mast cells –in anaphylactic rxns and certain parasitic
infections
• Eosinophils – produce major basic protein which is
toxic to parasites

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Granulomatous inflammation
• Characterized by formation of granulomas
• A granuloma consists of macrophages that are
transformed into epithelial-like cells surrounded by a
collar of lymphocytes and occasionally plasma cells
• Epithelioid cells may fuse to form giant cells with
multiple nuclei. Types of giant cells:
- Langhan’s type –nuclei arranged in a horse-shoe.
Seen in tuberculous infections
- Foreign body type –nuclei haphazardly arranged
- Warthin-Finkeldey type –have cytoplasm and nuclear
inclusion bodies. Seen in measles infection

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Granulomatous inflammation
• Distinctive pattern of chronic inflammation seen in a
limited number of conditions
• Mycobacterium tuberculosis granulomas are called
tubercles
• Characterized by central caseous necrosis
• Other examples of granulomatous inflammation:
- leprosy
- fungal infections
- parasitic infections
- syphilis
- cat-scratch disease