inflammation

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INFLAMMATION

Topic OutcomesAt the end of this lecture, students are able to :1.Describe orally the signs of inflammation2.Describe and differentiate in written between

acute and chronic inflammation3.Explain the morphological of types of

inflammation4.Describe in written the mechanism of healing

and repairing

CONTENTS

2.1: Definitions & Concepts Of Inflammation

2.2: Stages Of Inflammation

2.3: Mediators Of Inflammation

2.4: Morphologic Pattern Of Acute & Chronic

Inflammation

2.5: Repair Or Healing

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2.1: Definitions & Concepts Of Inflammation

• 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.

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• 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 mediated

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• Involves 2 basic processes (overlapping):

• Have protective role against injurious agents

• Cause considerable harm to the bodyeg; anaphylaxis, atherosclerosis etc

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Inflammatory response

healing

Signs of Inflammation

• The famous 4 cardinal signs of inflammation:(i) rubor (redness)(ii) tumor (swelling)(iii) calor (heat)(iv) dolor (pain)

Added latest – functio laesa (loss of function)

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Heat Redness Swelling Pain Loss Of Func.

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2.2: 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

(b) Intravascular activation of platelets(c) Polymorphonuclear neutrophils as

inflammatory cells

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• Chronic Inflammation- longer duration and occurs either :

(a) after the causative agent of acuteinflammation 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

macrophages)

I) ACUTE INFLAMMATION

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

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Infected toenail showing the characteristic redness and swelling associated with acute inflammation

(i) VASCULAR EVENTS• Alteration in the microvasculature (arterioles,

capillaries & venules)• Earliest response to tissue injury• Alterations includes:

(a) haemodynamic 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:

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Transient vasoconstriction

Persistent progressive vasodilatation

Local hydrostatic pressure

Slowing or stasis

Leucocytic margination

• Lewis Triple Response/ red line response;

(Eg: form stroking with a blunt point)

i. Red line : Appears a few second; Capillary & venules

dilatation

ii. Flare : Bright reddish appearance/flush

surrounding the red line; Anteriolar dilation

iii. Wheal : Swelling or oedema of the surrounding skin

occurring due to transudation of fluid into the extravascular space

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Triple response

(b) Altered vascular permeability• Vascular changes begin quickly after the

injury 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;

i. Hydrostatic pressure

ii. Oncotic pressure - protein

iii. Osmotic pressure

iv. Lymph flow

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Fluid interchange between blood and extracellular fluid (ECF). (HP = Hydrostatic

pressure, OP = Osmotic pressure)

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NO OEDEMA OEDEMA

Edema

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• MECHANISMS OF INCREASED VASCULAR PERMEABILITY

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

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a) Contraction of endothelial cells

• Microvasculature : venules• Response type :

Immediate transient (15-30 min)• Pathogenesis :

Histamine, bradykinin, other chemical mediators

• Examples : Mild thermal injury

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b) Retraction of endothelial cells

• Microvasculature : venules• Response type :

somewhat delayed (in 4 – 6 hrs)prolonged (for 24 hrs or more)

• Pathogenesis :Interleukin-1(IL-1)Tumor Necrosis Factor (TNF)

• Examples : In vitro experimental work only25

c) Direct injury to endothelial cells• Microvasculature : Arteriols, venules,

capillaries• Response type :

Immediate sustained leakage (immediate after injury prolonged (hrs to days)Delayed sustained leakage (delayed (2-12hrs) prolonged (hrs-days))

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• Pathogenesis :cell necrosis and detachment

• Examples : Moderate to severe burns, severe bacterial infection, radiation injury

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d) Endothelial injury mediated by leucocytes

• Microvasculature : venules, capillaries• Response type :

delayed, prolonged• Pathogenesis :

Leucocyte activation• Examples : pulmonary venules and capillaries

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e) Neovascularisation

• Microvasculature : All levels• Response type :

Any type• Pathogenesis :

Angiogenesis, vascular endothelial growth factor (VEGF)

• Examples : Healing, tumors

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ii) CELLULAR EVENTS • Cellular events; cells of the acute

inflammatory response are the neutrophils, monocytes & macrophages.

Polymorphonuclear neutrophils (PMNs)(within 24 hrs; Life long 24-48 hrs)

MonocytesMacrophages

(24-48 hrs; Survive much longer)30

• The movements of neutrophils out of the vessels & their role in combat can be divided into 5 steps;

i. Margination = ?

ii. Adhesion = ?

iii. Emigration/ diapedesis=?

iv. Chemotaxis = ?

v. Phagocytosis & degranulation=?

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• Concentrates the leucocytes adjacent to endothelial wall- Margination

• Adherence of inflammatory cell to the endothelium/ vascular basement membrane- Adhesion

• Neutrophil lodged between endothelial cell and basement membrane and escape out into the extravascular space- Diapedesis

• Chemotactic factor mediated transmigration of leucocytes to reach the interstitial tissue- Chemotaxis

• The process of engulfment of solid particulate material bt the cell (cell eating)- Phagocytosis 32

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 pneumonia

ii. Healing by scarrimg– tissue destruction is 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 – organised by dense fibrous tissue and get calcified

iv) Progression to chronic inflammation may follow acute inflammation, although signs of chronic inflammation may be present atthe 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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II) CHRONIC INFLAMMATION

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

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• Caused one of the following 3 ways:i) Chronic inflammation following acute inflammation – the tissue destruction is 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; repeated acute infection of gallbladder chronic cholecystitisiii) Starting de novo – infection with organisms of low pathogenecity (chronic from the beginning)

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• General features of Chronic inflammation:

i. Infiltration with mononuclear cells

Infiltrated by mononuclear inflammatory cells : phagocytes & lymphoid cells

phagocytes : circulating monocytes, tissue macrophages, epithelioid cells,

multinucleated giants cells

ii. Tissue destruction

Central feature of lesions

iii. Proliferative changes

Result of necrosis, proliferation of small vessels and fibroblasts; healing by fibrosis and collagen 41

Systemic effects of chronic inflammation

Associated with following systemic features:1. Fever – mild fever, loss of weight and

weakness2. Anemia – varying degree of anemia3. Leucocytosis - general 4. ESR – elevated in all cases5. Amyloidosis – long term cases of chronic

suppurative inflammation (secondary systemic (AA) amyloidosis

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Types of chronic inflammation

NON-SPECIFIC• Formation of granulation

tissue and healing by fibrosis

• Eg; Chronic osteomyelitis, Chronic ulcer

SPECIFIC• Injurious agent causes a

characteristic histologic tissue response

• Eg; tuberculosis, leprosy, syphilis

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Types of chronic inflammation (based on histological classification)

CHRONIC NON-SPECIFIC INFLAMMATION

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

CHRONIC GRANULOMATOUS INFLAMMATION

• Formation of granulomas• Eg; tuberculosis, leprosy,

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. Blastomycosis, Histoplasma capsulatum

iv. Inorganic metals or dusts e.g. Silicosis

v. Foreign body e.g. Vascular graft

vi. Unknown e.g. Sarcoidosis

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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-ˠ and IFN-ɑ)

• Monocyte chemotactic factor

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Accumulation of tissue macrophages (Increased recruitment from circulation, local

proliferation)

Macrophages activated by IFN-ˠ

Transformed to epithelioid cells, giant cells

GRANULOMA

Granuloma tissue

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• Examples of disorders associated with inflammation include;

i. Asthma

ii. Autoimmune diseases

iii. Hypersensitivities

iv. Pelvic inflammatory disease

v. Rheumatoid arthritis

vi. Transplant rejection

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2.3: 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 tightly regulated.

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• 2 types of chemical mediators of Acute inflammation;

i. Plasma-derived mediators e.g. kinin system,

coagulation & fibrinolytic system, complement

system.

ii. Cell-derived mediators e.g. vasoactive amines,

cytokines, platelet activating factor, growth factor.

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• Chronic inflammatory cells & mediators;

i. Macrophages

ii. T & B-lymphocytes

iii. Eosinophils

iv. Mast cells

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• Inflammatory cells release mediators such as;

i. Cytokines-

(IL-8, interferon-neutrophil)

ii. Vasoactive amines-

(histamine, serotinin- mast cell, basophil, platelet)

iii. Prostanoids-

(arachidonic acid metabolics)

iv. Reactive oxygen intermediates-

(released from activated neutrophil) 53

• 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 Abscess56

2.4: Morphologic Patterns Of Acute & Chronic Inflammation

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

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Serous Inflammation - effusion58

Serous Inflammation - effusion59

• Fibrinous inflammation; the formation of fibrin is striking e.g. in acute pleurisy.

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Fibrinous Inflammation61

• Purulent (Suppurative) 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 - PUS64

• 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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2.5: Repair Or Healing

• The processes that take place during & after the injury are;

i. Removal of dead & foreign material.

ii. Regeneration of injured tissue from cells

of the same type.

iii. Replacement of damage tissue by new

connective tissue.69

• Cells can be divided into 3 major groups;

i. Labile (continuous dividing) e.g. epithelial & blood cells.

ii. Stable (low level of replication; decrease or lose their ability to proliferate after adolescence) e.g. fibroblast, smooth muscle cells, bone & cartilage cells

iii. Permanent (never divide) e.g. nerve cells, cardiac myocytes.

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HEALING

• 2 processes:(i) Granulation tissue formation(ii) Contraction of wounds

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(i) Granulation tissue formation

• 3 phases :(a) PHASE OF INFLAMMATION

trauma, blood clots (site of injury)acute response :exudation of plasma,

neutrophils, monocytes (24 hours)

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(b) PHASE OF CLEARANCE- proteolytic enzymes from neutrophils- Autolytic enzymes from dead tissue

cells- Phagocytic activity : macrophages(function : clear of the necrotic tissue,

debris & RBCs)

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(c) PHASE OF INGROWTH OF GRANULATION2 main processes:i. Angiogenesis (neovascularisation) formation of new blood vesselsii. Fibrogenesis formation of fibrocytes and mitotic

division by fibroblasts; myofibroblasts In 6th days, more collagen is formed

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ii) Contraction of wounds

• Start after 2 -3 days; completed: 14th day• Wound reduced 80% of its original size• Contraction occur: rapid healing process• Factors under mechanism of wound

contraction: (a) dehydration(b) contraction of collagen(c) myofibroblasts

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WOUND HEALING

1. Healing by first intention (Primary union)characteristics:- clean & uninfected- surgical incised- without much loss of cells & tissue- edges of wound – surgical sutures

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2. Healing by second intention (Secondary union)Characteristics:- Large tissue defect- extensive loss of cells & tissues- not approximated by surgical sutures but left open

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• 5 stages of healing (primary Union);

i. Initial Haemorrhage

ii. Acute Inflammation response

iii. Epithelial changes

iv. Organization

v. Suture tracks

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• 6 stages of healing (secondary Union);

i. Initial Hemorrhage

ii. Inflammation phase

iii. Epithelial changes

iv. Granulation tissue

v. Wound contraction

vi. Presence of infection79

• Repair; regeneration of injured tissue by parenchymal cells of the same type.

• Replacement by connective tissue occur when repair by parenchymal regeneration alone cannot be accomplished.

• Involves production of Granulation tissue.

• Replacement of parenchymal cells with proliferating fibroblasts & vascular endothelial cells.

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Scars present on the skin, evidence of fibrosis & healing of a wound

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Granulation tissue

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Healing Skin wound

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Healing - Skin scar84

• Factors affecting healing;

i. Systemic e.g. age, nutrition, immune

status.

ii. Local e.g. infection, blood supply,

mobility, foreign body.

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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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