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Learning Outcomes
At the end of this lecture, students are able to : 1. define and list the signs of inflammation 2. explain the vascular and cellular events in the acute inflammation. 3. describe and differentiate in written between acute and chronic inflammation 4. explain the mediators of inflammation.

What is inflammation?
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The local response of living mammalian tissues to injury due to any agent.

Body defense reaction in order to eliminate or limit the spread of injurious agent as well as to remove the consequent necrosed cells and tissues.

Causes of inflammation; i. Physical agent e.g. mechanical trauma, radiation etc. ii. Chemical agent e.g. simple chemical poisons, organic poisons iii. Infective agents e.g. bacteria, viruses, parasites, their toxins iv. Immunological agents e.g. Ag-Ab reaction, cell Agmediated
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Inflammatory response has many players include; i. Circulating cells & plasma proteins ii. Vascular wall cells iii. Cells & extracellular matrix of the surrounding connective tissue

Earliest reactions of inflammatory response occurs in VASCULAR CONNECTIVE TISSUE. TISSUE.

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Stages Of Inflammation

INFLAMMATION

ACUTE INFLAMMATION

CHRONIC INFLAMMATION
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 Acute

inflammation

Short duration & represents the early body reaction and usually followed by repair The main features : (a) Accumulation of fluid & plasma at the affected site Intravascular activation of platelets (b) (c) Polymorphonuclear neutrophils as inflammatory cells

 Chronic

Inflammation longer duration and occurs either : (a) after the causative agent of acute inflammation persists for a long time (b) Stimulus that induces chronic inflammation from the beginning main features : presence of chronic inflammatory cells (lymphocytes, plasma cells and lymphocytes, macrophages) macrophages)

I) ACUTE INFLAMMATION
 The

changes can be conveniently described under: (i) Vascular events (ii) Cellular events

Infected toenail showing the characteristic redness and swelling associated with acute inflammation
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Signs of Inflammation
famous 4 cardinal signs of acute inflammation: (i) rubor (redness) (ii) tumor (swelling) (iii) calor (heat) (iv) dolor (pain) Added latest functio laesa (loss of function)
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 The

Heat

Redness Swelling

Pain

Loss Of Func.
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(i) VASCULAR EVENTS

 Alteration

in the microvasculature (arterioles, capillaries & venules) venules)  Earliest response to tissue injury  Alterations includes: (a) haemodynamic changes (b)changes (b) changes in vascular permeability

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(a) Haemodynamic Changes

 Earliest

features of inflammatory response result from changes in the vascular flow and calibre of small blood vessels in the injured tissue

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The sequence of these changes: Transient vasoconstriction Persistent progressive vasodilatation Local hydrostatic pressure Slowing or stasis Leucocytic margination
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Lewis Triple Response/ red line response

Red line Flare wheal

Appears a few second; Capillary & venules dilatation

Bright reddish appearance appearance/flush surrounding the red line; Arteriolar dilation Swelling or oedema of the surrounding skin occurring due to transudation of fluid into the extravascular space
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Triple response

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(b) Altered vascular permeability



Vascular changes begin quickly after the injury rates, but may develop at variables rates, depending on the nature & severity of the original injury. The interchange of fluid between the vascular & extra vascular space results from balance of fluid into the vascular space or out into the tissues depend on 4 different types of pressure.

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Changes vascular permeability Hydrostatic pressure ? Osmotic pressure ? Oncotic pressure ? Lymph flow ?
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Fluid interchange between blood and extracellular fluid (ECF). (HP = Hydrostatic pressure, OP = Osmotic pressure)

NO OEDEMA

OEDEMA
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 MECHANISMS

OF INCREASED VASCULAR PERMEABILITY

Endothelial cell contraction (ii) Endothelial cell retraction (iii) Direct injury to endothelial cells (iv) Endothelial injury mediated by leucocytes (v) Neovascularisation
(i)

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ii) CELLULAR EVENTS



Cellular events; cells of the acute inflammatory events; neutrophils, response are the neutrophils, monocytes & macrophages. macrophages. Polymorphonuclear neutrophils (PMNs) (within 24 hrs; Life long 24-48 hrs) 24-

Monocytes Macrophages (24(24-48 hrs; Survive much longer)

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 The

movements of neutrophils out of the vessels & their role in combat can be divided into 5 steps; steps; i. Margination ii. Adhesion ? iii. Emigration/ diapedesis ? iv. Chemotaxis ? v. Phagocytosis & degranulation ? ?

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THE INFLAMMATION PROCESS

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Neutrophil Margination
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FATE OF ACUTE INFLAMMATION



Acute inflammation generally has one of FOUR (4) outcomes; i. Resolution complete return to normal/ tissue changes are slight and cellular changes are reversible eg; resolution in lobar eg; pneumonia ii. Healing by scarrimg tissue destruction is scarrimg extensive, no tissue regeneration; healing by fibrosis
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iii) Suppuration the progression process of severe necrosis cause by pyogenic bacteria; neutrophilic infiltration; form an abcess; abcess; abcess organised by dense fibrous tissue and get calcified iv) Progression to chronic inflammation may follow acute inflammation, although signs inflammation, of chronic inflammation may be present at the onset of injury; healing proceed side by side.
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An abscess on the skin, showing the redness and swelling characteristic of inflammation. Black rings of necrotic tissue surround central areas of pus

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Assessment
 What

is giant cell?

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II) CHRONIC INFLAMMATION

 Chronic inflammation; inflammation;

prolonged process in which tissue destruction and inflammation occur at the same time. time.

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 Caused one of the following 3 ways: ways:

inflammation following acute i) Chronic the tissue destruction is inflammation extensive, extensive, or bacteria survive & persist in small numbers at the site of acute inflammation ii) Recurrent attacks of acute inflammation repeated bouts of acute inflammation eg; eg; repeated acute infection of gallbladder chronic cholecystitis iii) Starting de novo infection with organisms of beginning) low pathogenecity (chronic from the beginning)

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General features of Chronic inflammation: inflammation: i. Infiltration with mononuclear cells Infiltrated by mononuclear inflammatory cells : phagocytes & lymphoid cells phagocytes : circulating monocytes, tissue monocytes, macrophages, epithelioid cells, multinucleated giants cells ii. Tissue destruction ii. Central feature of lesions iii. Proliferative changes iii. Result of necrosis, proliferation of small vessels and fibroblasts; healing by fibrosis and collagen fibroblasts;
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Types of chronic inflammation

NON-SPECIFIC NONFormation of granulation tissue and healing by fibrosis  Eg; Chronic osteomyelitis, Eg; osteomyelitis, Chronic ulcer
 

SPECIFIC Injurious agent causes a characteristic histologic tissue response  Eg; tuberculosis, leprosy, Eg; syphilis

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Types of chronic inflammation (based on histological classification)

CHRONIC NON-SPECIFIC NONINFLAMMATION


CHRONIC GRANULOMATOUS INFLAMMATION

Characterised by: (a) non-specific noninflammatory cell infiltration eg; chronic eg; osteomyelitis, osteomyelitis, lung abcess (b) Infiltration by polymorphs and abcess formation Eg; Eg; Actinomycosis

Formation of granulomas  Eg; tuberculosis, leprosy, Eg; syphilis, sarcoidosis



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Granulomatous Inflammation


Granulomatous inflammation; mechanism whereby the body deals with certain indigestible bacteria, fungi, or foreign particles. Examples; i. Bacteria e.g. Tuberculosis, Leprosy ii. Parasitic e.g. Schistosomiasis iii. Fungal e.g. Histoplasma capsulatum Fungal iv. Inorganic metals or dusts e.g. Silicosis v. Foreign body e.g. Vascular graft

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INJURY (e.g; by M. tuberculosis, talc Failure to digest agent

Weak acute inflammatory response

Persistence of injurious agent

T cell-mediated immune response

Poorly digestible agent

Activation of CD+4 T cells (release of lymphokines IL-1, IL-2. growth factors IFN- and IFN- ) Monocyte chemotactic factor
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Accumulation of tissue macrophages (Increased recruitment from circulation, local proliferation)

Macrophages activated by IFN-

Transformed to epithelioid cells, giant cells

GRANULOMA
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Granuloma tissue
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What is Mediator ???

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Mediators Of Inflammation


What are mediators? i. May be circulating in the plasma or may be produced locally by cells at the site of inflammation. ii. Induce their effects by binding to specific reactors on target cells. iii. May stimulate target cells to release secondary effector molecules. iv. May act on only one or a very few targets. v. Function is generally tighly regulated.
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2 types of chemical mediators of Acute inflammation; i. Plasma-derived mediators e.g. kinin system, Plasmacoagulation & fibrinolytic system, complement system. Cellii. Cell-derived mediators e.g. vasoactive amines, cytokines, platelet activating factor, growth factor.

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Inflammatory cells release mediators such as; i. CytokinesCytokines-

(IL-8, interferon-neutrophil) IL- interferonii. Vasoactive aminesamines(histamine, serotinin- mast cell, basophil, platelet) serotininbasophil, iii. ProstanoidsProstanoids(arachidonic acid metabolics) iv. Reactive oxygen intermediatesintermediates(released from activated neutrophil) neutrophil)
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If the mediators in the inflammatory response are successful; i. Invading & infectious agents will be removed. ii. Damaged tissues will be disposed of. iii. New tissue will be induced to form. iv. New blood supply to the area will be established.

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Chronic inflammation cells

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Chronic Inflammation Lung Abscess

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Morphologic Patterns Of Acute & Chronic Inflammation

Serous inflammation; excessive clear watery inflammation; fluid with a variable protein content but no fibrin e.g. pleural effusion associated with tuberculosis.

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Serous Inflammation - effusion

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Serous Inflammation - effusion

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 Fibrinous inflammation; the inflammation;

formation of fibrin is striking e.g. in acute pleurisy.

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Fibrinous Inflammation
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 Purulent (Suppurative) inflammation; inflammation;

production of pus is the main characteristic e.g. abscess & acute apendicitis.

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Purulent Inflammation - PUS

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Purulent Inflammation - PUS

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 Ulceration; complication of

many disease

process
 Divided into 2 groups;

i. Simple ulcer ii. Malignant (cancerous) ulcer

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A skin ulcer resulting from infection with Corynebacterium diphtheriae

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Mouth Apthus Ulcer

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Gastric Ulcer
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"Each time you are honest and conduct yourself with honesty, a success force will drive you toward greater success. Each time you lie, even with a little white lie, there are strong forces pushing you toward failure."
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THANK YOU

FOR YOUR ATTENTION

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