7 basics of inflammation

7/31/2019 7 Basics of Inflammation

1/78

INFLAMMATION

By :

Gaurav Kansal

PG student 2nd Yr


2/78

Definition

Defined as the local response of living tissues

to injury due to any agent.

Inflammation is 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 .


3/78

DARK SIDE OF INFLAMMATION

Although, inflammation is a protective

reaction, it can even prove to be fatal in the

form of life threatening anaphylactic reactionsto insect bites or drugs as well as in certain

chronic diseases like rheumatoid arthritis or

atherosclerosis.


4/78

PROVOCATION OF

INFLAMMATION

1. Physical agents: HeatCold

Radiations

Mechanical Trauma

2. Chemical agents: Organic & Inorganic poisons

3. Infective agents: Bacteria

Viruses

Parasites

4.Immunological agents: Antigen antibodyreactions

Cell mediated reactions


5/78

CARDINAL SIGNS OF

INFLAMMATION

As given by CELSUS :-

Rubor (redness)

Tumor (swelling)Calor (heat)

Dolor (pain)

As given by VIRCHOW:-Functiolaesa (loss of function)


6/78

Cells OF INFLAMMATION

1. Circulating blood cells

a. Polymorphonuclear neutrophils.

b. Eosinophils

c. Basophils

d. Lymphocytes

e. Monocytesf. Thrombocytes


7/78

2. Plasma proteins

a. Clotting factors

b. Kininogens

c. Complement components.

3. Vascular wall cells

a. Endothelial cells

b. Smooth muscle cells


8/78

4. Connective tissue cells

a. Macrophagesb. Mast cells

c. Lymphocytes

d. Fibroblasts.5. Extracellular matrix

a. Fibrous structural proteins (collagen &elastin)

b. Proteoglycans

c. Adhesive glycoprotein ( fibronectin)


9/78

TYPES OF INFLAMMATION

Depending, upon the intensity of injury,duration of the response, & defence capacity

of the host , inflammation can be classified

as :(i) Acute inflammation

(ii) Chronic inflammation


10/78

ACUTE INFLAMMATION

Short duration (few minutes to few days ).

Characterized by exudation of fluid & plasma

proteins.

Neutrophils are the predominant cell type

Usually followed by repair.


11/78

CHRONIC INFLAMMATION

Longer duration (days to years).

Macrophages & lymphocytes are thepredominant cells.

Characterized by the vascular proliferation &

scarring.


12/78

ACUTE INFLAMMATION

It is better described under two headings :

1.Vascular events: Vasodilation after a transient vasoconstriction

(cause of redness & heat) Increased vascular permeability (cause of oedema /

swelling).

2. Cellular events:

Extravasation of leukocytes from the vessels to theextravascular space

Phagocytosis and degranulation.


13/78

VASCULAR EVENTS

These changes begin immediately after injury but maydevelop at variable rates depending upon the severityof the injury.

Vascular events include:

1.VASODILATION: Initial transient vasoconstriction (from 3-5 sec. to 5

min.)

Followed by vasodilation of mainly arterioles but tolesser extent that of venules & capillaries.

The changes are seen within half an hour ofinjury.


14/78

Vasodilation results in increase in the blood

volume of microvascular bed (responsible for

redness and heat) which increases the local

hydrostatic pressure.

Due to increased hydrostatic pressure, the

microvasculature becomes more permeable to

the leaking of protein rich fluid into theextravascular tissues.

So, red cells becomes more concentrated,

thereby increasing the viscosity of blood and

slowing or stasis of circulation.


15/78

As stasis develops, leukocytes begin to settle

out of the flowing blood and accumulates

along the vascular endothelial surface

(margination) and finally squeezes themselvesthrough the gaps into the extravascular tissues

(emigration).


16/78

The loss of vascular proteins reduces theintravascular osmotic pressure and increases

the interstitial osmotic pressure which

facilitates more outflow of water and ions into

the extravascular tissues (oedema).


17/78


18/78

Leukocyte dependant endothelial injury :Occurs as a consequence of leukocyteaccumulation during inflammatory response.

The leukocytes releases toxic oxygen species& proteolytic enzymes which then causes

endothelial injury or detachment.


19/78

Leakage from new blood vessels:

During angiogenesis, the vessels sprouts

remain leaky until proliferating endothelial

cells differentiate sufficiently to form

intercellular junctions.


20/78

CELLULAR EVENTS

The extravasation of the leukocytes from the vascularcompartment to the extravascular compartment

occurs as follows:

1.Margination and rolling.

2.Adhesion.

3.Emigration.

4.Chemotaxis

5.Phagocytosis & degranulation.


21/78


22/78

Margination and rolling

Under normal conditions, the normal axialflow consists of a central stream of cells and cellfree plasma layer closer to the vessel wall.

As a result of stasis (due to increased vascular

permeability) and because of the fact that RBCmove at a faster speed than WBC , central streamof cells widens and the peripheral plasma zonenarrows ,so leukocytes get a better chance to

interact with the endothelial cells i.e. margination.Finally, the leukocytes tumble on the

endothelial surface and transiently stick along theway (rolling).


23/78

ADHESION

After pavementing, leukocytes stick firmly to

the endothelial cells. Actually, injury

neutralizes the normal negative charge on the

leukocytes and endothelial cells so as to cause

adhesion.Adhesion is mediated by the molecules of

immunoglobulin superfamily on endothelial

cells that interacts with integrins present onleukocytes.


24/78

EMIGRATION

After sticking to the endothelial cells, theleukocytes move along the endothelial surface

till a suitable site between the endothelial cells

is found, wherefrom the leukocytes throw out

cytoplasmic pseudopods and squeeze

themselves between the cells at intercellular

junctions.

PECAM-1(platelet endothelial cell adhesionmolecule-1)belonging to immunoglobulin

superfamily mediates this process.


25/78


26/78

CHEMOTAXIS

In this process, the leucocytes are directedtowards the foci of injury along a chemical

gradient.

Different leucocytes have different chemotacticsubstances :(i) Agents for Neutrophils :

C5a productLeukotrienes B4


27/78

(ii) Agents for Monocytes:

C5a products

Bacterial products

Products of activated Clotting,Fibronolytic, & Kinin systems

Lymphokines from sensitized

lymphocytes


28/78

(iii) Agents for Eosinophils:

Eosinophil chemotactic factor ofAnaphylaxis (ECF-A)

Parasitic products

Products of Complements


29/78

PHAGOCYTOSIS &


30/78

PHAGOCYTOSIS &

DEGRANULATION

Defined as the process of engulfment of solid

particulate material by the cell eating cells i.e

phagocytes.They are:-

(i) Microphages i.e Neutrophils which

arise early in acute inflammation

(ii) Macrophages i.e Tissue monocytes in

late inflammation .


31/78

STAGES IN PHAGOCYTOSIS


32/78

Phagocytosis is accomplished by :-

(i) OPSONISATION i.e recognition &attachment of the particulate to

the leucocytes.

(ii) ENGULFMENT(iii) KILLING & DEGRADATION of the

ingested material


33/78

ATTACHMENT stage:-

The phagocytic cells as well as the micro-organisms to be ingested are negatively

charged and as such repel each other. In order

to establish a bond between the two, themicro-organisms get coated with OPSONINS

(serum proteins) which facilitates binding

between the two.

ENGULFMENT STAGE


34/78

ENGULFMENT STAGE

The opsonised particles bound to the surface of

phagocytes is now ready to be engulfed. This

is done by the formation of cytoplasmic

pseudopods by the phagocyte around the

particle to be ingested forming a phagocytic

vacuole.


35/78


36/78

KILLING & DEGRANULATION

STAGE

Now, killing ,digestion & degradation of themicro-organisms occurs by varioushydrolytic enzymes secreted by leucocytes.

The antimicrobial agents act by either of thetwo mechanisms:-

(i) oxygen dependant bacteriocidal

mechanisms(ii) oxygen independent bactericidal

mechanisms


37/78

CHEMICAL MEDIATORS OF

INFLAMMATION

The various mediators that lead to

vasodilation, increased permeability,

chemotaxis, fever, pain, & even tissue

damages are classified into two groups:-

(i) Mediators released by the cells locally

at the site of inflammation.

(ii) Mediators originating from plasma

synthesized by liver.


38/78

LOCAL MEDIATORS

1. Histamine:

Present in the granules of mast cells, basophils& platelets.

Released from these cells in response to various

stimuli like

(i) physical injury like trauma or heat.

(ii) Immune reactions binding IgE receptors

on mast cells.(iii) C3a, C5a (anaphylatoxins) fragments of

complement system.


39/78

Actions of histamine :-

(i) Vasodilation

(ii) Immediate increased vascular permeability

(iii) Itching(iv) Pain


40/78

2. Serotonin (5- hydroxytryptamine )

Secreted from platelets.

Present in tissues like chromaffin cells of

GIT, spleen, nervous tissue, mast cells &

platelets.Its actions are same like histamine but is a

less potent mediator.

3 Arachidonic acid metabolites


41/78

3.Arachidonic acid metabolites

It is a fatty acid.

Source is either directly from diet or by the

conversion of essential fatty acid linoleic acid

to arachidonic acid.

Metabolites are formed by one of the following

two pathways:-

via lipooxygenase pathway or

via cyclooxygenase pathway.


42/78

4.LYSOSOMAL ENZYMES

The inflammatory cells like neutrophils and

monocytes contain lysosomal granules which

on release elaborate a variety of mediators of

inflammation.

These may be released during cell death by

leakage during the formation of phagocytic

vacuole .


43/78

5.PLATELET ACTIVATING

FACTORS

It is released from membrane phospholipids ofneutrophils, monocytes, basophils, endothelium &platelets.

Apart from its action on platelet aggregation , thevarious action of PAF , as mediators of inflammationare

(i) increased vascular permeability(ii) enhanced leucocyte adhesion .

(iii) leukocyte degranulation .

(iv) oxidative burst .


44/78

1.KININ SYSTEM

First kallakrein is formed from plasma prekallakrein

by the action of prekallakrein activator which is a

fragment of factor XIIa. Kallakrein then acts on

high molecular weight kininogen (HMWK) to formbradykinin which induces

Vasodilation

Smooth muscle contraction

Increased vascular permeability

Pain


45/78

2.CLOTTING SYSTEM

Factor XIIa initiates the clotting cascade by

forming fibrinogen which is acted upon by the

thrombin to form fibrin & fibrinopeptides .

The action of fibrinopeptides are:

Increased vascular permeability

Chemotaxis for leukocytes

Anticoagulant activity.


46/78

3.FIBRINOLYTIC SYSTEM

This system is activated by the plasminogen

activator, the source of which is kallikrein ofkinin system, which converts plasminogen toplasmin. Plasmin further breaks fibrin to

fibrinopeptides & fibrin split products.The various actions of plasmin are :

splits Complement C3 to form C3a .

degrades fibrin to form fibrin splitproducts which increases vascularpermeability & are chemotactic forleukocytes.


47/78

4.COMPLEMENT SYSTEM

The activation of complement system occurseither

by the classic pathway through antigen antibody complexes or

by alternate pathway via nonimmunological agents like bacterial toxins ,venoms, IgA .

After activation , complement system yieldsC3a &C5a which are anaphylatoxins .


48/78

The actions of anaphylatoxins includes :-Release of histamine from mast cells and

basophils.

Increased vascular permeability causingedema.

C5a is chemotactic for leukocytes .

OUTCOME OF ACUTE


49/78

OUTCOME OF ACUTE

INFLAMMATION

Acute inflammation has got one of the three

outcomes depending upon:

the nature & intensity of injury

the site & the tissues affectedthe ability of the host to elicit a response

viz

(i) Resolution(ii) Scarring / Fibrosis

(iii) Progression to chronic inflammation

RESOLUTION


50/78

RESOLUTIONIt occurs when :

The injury is limited or short lived.

The tissue is capable of replacing any irreversibly

injured cells

The various chemical mediators are neutralized

Vascular permeability restored

.

Lymphocytic drainage & macrophagic ingestion

of necrotic debris lead to the clearance of oedema

fluid and inflammatory cells

SCARRING / FIBROSIS


51/78

SCARRING / FIBROSIS

It occurs when :

The destruction is extensive

The tissues donot have the capacity to

regenerate.

Extensive fibrinous exudates may not be

completely absorbed and are organized by the

ingrowth of connective tissue or fibrosis .

Abscess formations also end in scarring .

PROGRESSION TO CHRONIC


52/78

PROGRESSION TO CHRONIC

INFLAMMATION

Sometimes the signs of chronic inflammation

are present at the onset of injury eg :- in viral

infections, immune responses of self antigens.

Chronic inflammation may itself be followed

by the regeneration of normal structure and

function (regeneration ) or may lead to

scarring .

CHRONIC INFLAMMATION


53/78

CHRONIC INFLAMMATIONConsidered as the inflammation of prolonged duration

(weeks to months to years ) in which acute inflammation ,tissue injury and healing proceeds simultaneously .

chronic inflammation is characterized by the following :

Infiltration with chronic inflammatory cells macrophages,lymphocytes & plasma cells.

Tissue destruction by inflammatory cells.

Repair involving angiogenesis & fibrosis.

TYPES OF CHRONIC


54/78

TYPES OF CHRONIC

INFLAMMATION

Conventionally,

(i) Non-specific eg:-

chronic osteomyelitis

chronic ulcers

(ii) Specific eg:-

tuberculosis

leprosy

syphilis

CELLS OF CHRONIC


55/78

CELLS OF CHRONIC

INFLAMMATION

1.MACROPHAGES :Main cells in chronic inflammation. These are

tissue cells that are derived from the circulatingmonocytes after their emigration from the blood

stream .

Scattered diffusely in :-

Connective tissues (Histiocytes )

Liver cells (Kuffers cells )

Spleen & lymph nodes (Sinus histiocytes )

In lungs (alveolar macrophages )

In skin (Langerhans cells ) etc


56/78

Within 24-48 hours of acute inflammation, themonocytes begin to emigrate at the site of

injury

When they reach the extravascular tissues,they undergo transformation into larger cells

called macrophages .

They are also called epitheloid macrophages

because under light microscope withhematoxylin & eosin staining they resemblesquamous cells .


57/78

Macrophages on activation by lymphokines releasedby T lymphocytes or by non immunologic stimulisecretes a number of biologically active substanceslike:

(i) Proteases (collagenase & elastase ) which

degrades collagen and elastic tissues(ii) Plasminogen activators which activates

fibrinolytic system

(iii) Complement products

(iv) Coagulation factors (factor V thromboplastin )

which converts fibrinogen to fibrin .

(v) Chemotactic agents for others leucocytes


58/78

When the macrophages fail to deal with the

foreign particles , they fuse together & forms

multinucleated giant cells.

The various giant cells are:-

(i) Foreign body giant cells.

(ii) Langhans giant cell.

(iii) Tumor giant cells.

(iv) Touton giant cells.

(v) Miscellaneous.


59/78

1.Foreign body giant cells :

Contains numerous nuclei upto 100 whichare uniform in shape and size resembling the

nuclei of macrophages which are scattered

throughout the cytoplasm .Seen commonly in foreign body tissue

reactions.


60/78


61/78

3. Tumor giant cells :

They are larger cells, have numerous hyper

chromatic nuclei which are derived from the

dividing nuclei of neoplastic cells and from

the macrophages .

Seen commonly in carcinoma of liver,

various sarcomas etc.


62/78


63/78

2.LYMPHOCYTES

These are the second most numerous cells .

Apart from the blood they are also found in spleen,

thymus ,lymph nodes & lymphoid tissue of the gut .

They have scanty cytoplasm and consists entirely ofnucleus .

Besides, their role in antibody formation (B

lymphocytes ) and in cell mediated immunity (T

lymphocytes), they participate in chronic inflammation

and later stages of acute inflammation


64/78

4 EOSINOPHILS


65/78

4.EOSINOPHILS

These are characteristically found ininflammatory site around parasitic infectionsor as in immune reaction mediated by IgE

associated with allergies.Their emigration is driven by adhesionmolecules similar to those used by neutrophils.

Eosinophil granules contain major basicprotein (MBP) that is toxic to parasite but mayalso cause lyses of epithelial cell.

5 MAST CELLS


66/78

5.MAST CELLS

They are widely distributed in connective

tissues and can participate in both acute and

chronic inflammatory responses.

Mast cells are armed with IgE against certain

antigens. When these antigens are

encountered, the mast cell releases histamine

and arachidonic acid metabolites that starts the

early vascular changes of acute inflammation .


67/78

Mast cells elaborate cytokines like TNF thereby

participating in more chronic responses.

Mast cells also play beneficial role in variety

of infections particularly those involving the

parasite.

MORPHOLOGICAL PATTERNS


68/78

MORPHOLOGICAL PATTERNS

OF ACUTE AND CHRONIC

INFLAMMATION

Various types of inflammation (acute and

chronic) can generally be seen depending upon(i) The severity of the inflammatory

response

(ii) Its specific cause(iii) Tissues involved


69/78

TYPES :

Serous inflammationFibrinous inflammation

Suppurative inflammation

Ulceration


70/78

SEROUS INFLAMMATION :

Characterized by out pouring of watery, lessproteinous fluid (effusion) .

Derived either from the serum or mesothelial

cells, lining of various cavities (pleural,pericardial, peritoneal).

Examples are skin blisters either from a sun

burn or from a viral infection .


71/78

FIBRINOUS INFLAMMATION :

Occurs as a result of serious injury .

Vascular permeability is greatly increased allowing

even fibrinogen to pass through the endothelium .

Fibrinous exudates may be degraded by fibrinolysisand the accumulated debris removed by macrophages

resulting in resolution (restoration of normal tissue

structure) .

However, failure to completely remove the fibrin

results in the ingrowth of fibroblasts & blood vessels

leading to scarring . (organization) .

SUPPURATIVE (PURULENT


72/78

SUPPURATIVE (PURULENTINFLAMMATION) :

Characterized by the presence of large amounts of

purulent exudates (pus) consisting of neutrophils,

necrotic cells and edematous fluid .

Abscesses are focal collections of pus that may becaused by the deep seeding of pyogenic organisms

(staphylococcus) into the tissue or by secondary

infections of necrotic foci .


73/78

ULCERATION :

This condition occurs when any epithelialsurface becomes necrotic and eroded often

associated with sub epithelial acute or chronic

inflammation .

May arise as a consequence of toxic or

traumatic injury to the epithelial surface

(peptic ulcers) or due to the vascular

comprising conditions (diabetic foot) .


74/78

Granulomatous inflammation

Characterized by formation of granulomas

It is a distinctive pattern of chronic inflammationcharacterized by aggregates of activated

macrophages that assume a squamous like(epitheloid) appearance.

Granuloma is defined as a circumscribed, tinylesion,1mm in diameter composed ofepitheloid cells, rimmed at periphery bylymphoid cell.

Common Granulomatous


75/78

Common Granulomatous

Conditions

1. Bacterial :

Tuberculosis

Leprosy

Syphilis

Actinomycosis

Cat scratch fever


76/78

2. Fungal:

Blastomycosis

Cryptococcosis

3. Parasitic :

Schistosomiasis


77/78

4. Miscellaneous :

Sarcoidosis

Crohns disease

Silicosis

Foreign body granuloma


78/78

REFRENCES

Textbook of pathology - Harsh MohanAndersons Textbook of pathology

Pathologic basis of disease - Robbins

7 basics of inflammation

Documents