Inflammation Part I BY Prof.SOHEIR SAAD

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INFLAMMATION
PROF.SOHEIR SAAD
PART I
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INFLAMMATION
Definition

• It is cellular and vascular reaction of
• the living tissues to an irritant aiming
• of getting rid of it.

• It is essentially a protective beneficial
• process, aiming at combating many
• infections and limiting the effects of
• many toxic and injuries agents.

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CAUSES OF INFLAMMATION

• All the causes of cell injury cited earlier
  also
• provoke inflammation.

• Hypoxia (deficiency of oxygen) due to
• (i) Ischaemia
• (ii) decrease of oxygen carrying capacity
  of
• blood due to anaemia, cardiac or
• respiratory failure and CO
  poisoning.
• 2. Physical agent burns, deep cold, radiation,
• mechanical trauma and electric shock.
• 3. Biological agents e.g. viruses, bacterial
• toxins, fungi and parasites.
• 4. Chemical agents
• and drugs e.g. alkalis, acids,
  insecticides,
• alcohol and narcotic drugs air pollutants

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CAUSES OF INFLAMMATION
5. Endogenous toxins as in case of uremia,
jaundice and diabetic ketosis. 6. Immunologic
reactions (hypersensitivity). 7.
Nutritional imbalance such as protein
calorie malnutrition, starvation, obesity,
diabetes mellitus an deficiency of other
substances and vitamins. 8. Genetic
abnormalities as in Down syndrome sickle
cell anemia.
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Depending on the nature of the stimulus and
the effectiveness of the initial reaction in
eliminating the stimulus or the damaged tissues.
I-Acute Inflammation II-Chronic
Inflammation III-Subacute Inflammation
TYPES OF INFLAMMATION
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Chronic Inflammation
Acute Inflammation

Presence of lymphocytes

• Is rapid in onset
• (typically minutes)

• insidious in onset

• Short duration
• lasting for hours or a few days

• Longer duration

• Characterized by
• exudation of fluid
• plasma (edema)
• emigration of PNLs

• Characterized by

Macrophageproliferation of bl.v. fibrosis
tissue necrosis.
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Inflammation
Acute inflammation
Chronic Inflammation
Acute Non suppurative
Chronic Specific
Chronic Non-Specific
Acute suppurative
Catarrhal ,Serous fibrinous,Serofibrinous Member
nous ,Allergic and hemorrhgic
GRANULOMA
Localized
Diffuse
Abcsess Carbuncle
Cellulites
NON Infective Sarcoidosis Forgein body
Infective e.g T.B ,S,B
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Inflammation
Acute inflammation
Chronic Inflammation
Acute Non suppurative
catarrhal
Serofibrinous
Chronic Specific
Chronic Non-Specific
Serous
Acute suppurative
Allergic
Fibrinous
Membernous
Hemorrhgic
GRANULOMA
Localized
Diffuse
Abcsess Carbuncle
NON Infective Sarcoidosis Forgein body
Cellulites
Infective e.g T.B ,S,B
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Basophil
Neutrophil
Eosinophil
Lymphocyte
Plasma cell
Monocyte
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Microcirculation cellular component of the
blood
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ACUTE INFLAMMATION
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• Acute inflammation is a an early immediate
  rapid host response that serves to deliver
  leukocytes and plasma proteins, such as
  antibodies, to sites of infection or tissue
  injury.

• The morphologic hallmarks of all acute
  inflammatory reactions are dilation of small
  blood vessels, slowing of blood flow, and
  accumulation of leukocytes and fluid in the
  extravascular tissue

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Reaction of body to Acute inflammation

• Effects of an Irritant-
• Local reaction of the tissue to the irritant
• (A) Local tissue injury
• necrosis with the release of chemical
  mediators.
• (B) Local vascular phenomenon
• Vascular
• Cellular Stages
• II. General (Systemic) reaction of the body

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Local Vascular Phenomenon

Formation of Inflammatory Exudates
Change in Vascular Bed Change in the Flowing
Blood
Change In the Circulating Blood
Cellular Stages 1.Margination. 2.Pavementing
and rolling 3.Emigration 4.Chemotaxis. 5.phagocyt
osis

• 1.Transient
• Vasoconstriction
• 2.Stage of vasodilatation
• 3.Increased capillary bed
• Blood Flow
• 5.Slowing of Blood Flow

Fluid Part
Cellular Part
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CHANGE IN VASCULAR BED AND Changes OF BLOOD
FLOWING VASCULAR STAGE

• is an early immediate reaction triggered or
  initiated by
•  Local tissue injury Necrosis with
• the release of chemical mediators.
• 1.Starts by short time of vasoconstriction
• Due to
• -Stimulation of V.C Nerve
• -Direct Action of Toxins on the vessels wall

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• 2. Vasodilation
• Due to
• -Reflex Stimulation of vasodilator nerve and
  paralysis of
• vasoconstrictor nerve
• -Action of histamine and h- like substance
  from damaged tissue
• leading to Increased blood flow
• first involving the arterioles and then leads to
  opening of the capillaries .
• this causes heat and redness (erythema) at the
  sit of inflammation.

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• 3. Increased Cappillary bed with
• increased permeability
• of the microvasculature
• (the venular end of the capillaries),this
• quickly follow vasodilation
• Allowing fluid and blood proteins to
• move into the extravascular tissues
• The increased permeability of the
• capillaries occurs because the
• endothelial cells separate from one
• another at their edges.

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• The main chemical mediators
• which are responsible for
• vascular dilation and
• increased permeability are
• Histamine and Serotonin,
• Prostaglandins, and
• Nitric oxide (NO), on vascular
• smooth muscle.

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4-These changes (Vasodilation and Increased
permeability) result in Increased blood flow
(Active Hyperamia ) 5- Then slowing
of circulating blood , a condition termed stasis
, which is seen as vascular congestion (producing
localized redness) upon examination of the
involved tissue .
So Stasis of the blood flow takes place as a
result of (a) The sustained vasodilatation,
(b) Increased capillary bed, (c) Increased blood
viscosity secondary to loss of plasma in
the tissues, (d) Swelling of the capillary
endothelium. This is more noticeable in the
venular end.(Direct Toxin effect )N.B. Normally
only about 10 of the capillary bed is
functioning at a time.
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Endothelial cells separate from one another at
their edges.
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• Retraction of endothelial
• Cells
• Endothelial injury

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CHANGE IN THE CIRCULATING BLOOD
(Cellular Stage)
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• The journey of leukocytes from the vessel lumen
  to the interstitial tissue, called extravasation,
  
• This occurs in many steps and under the effects
  of many chemical mediators, and cytokines

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• Sequence of leukocyte events
• Margination.
• Pavementing or rolling.
• Emigration.
• Chemotaxis.
• Phagocytosis and intracellular degradation.
• Synthesis of biochemical mediators.
• Extracellular release of Leukocyte Products

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• 1.MARGINATION
• Leukocytes fall out of the central column
  tumble slowly to the periphery of the vascular
  lumen, until they are in apposition to the
  surface of endothelial (leave the axial stream)
• Because blood flow slows early in inflammation
  (stasis), hemodynamic conditions change and more
  white cells assume a peripheral position along
  the endothelial surface.

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Margination of leukocytes occurs
Laminar blood flow maintain PNLs against the
venular wall
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• 2.Pavmenting adhesion and
• Rolling of The leukocytes along the
  endothelial lining of blood vessels.
• starts by Rolling of The leukocytes under the
  effect of adhesion molecule (selectins),
• Then become activated and tightly adhere to
  endothelium by (ICAM-1,and VCAM-1) present on the
  endothelial cells and by (integrins) present on
  the neutrophil.

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• The leukocytes become adherent to the
• endothelial cells.
• Adhesion to the endothelium is at first
• loose, causing Rolling of the leukocytes
• on the lumen of the vessel.
• When the adhesion becomes firmer, the
• leukocytes become stationary can
• then begin to migrate through the
• endothelium into the site of inflammation.
• Leukocytes become adherent to the
• endothelial cells through Adhesion molecules

Pavementation
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Adhesion Molecules
There are 4 main groups of adhesion
molecules Selectins on endothelium, bind
mucin-like ligands Mucin-like ligands on
leukocytes, bind selectins. Integrins on
leukocytes, bind immunoglobulin adhesion
molecules. Immunoglobulin adhesion molecules on
endothelium, bind integrins.
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Rolling (Weak Adhesion

• Rolling is due to binding of Selectins
• to mucin-like ligands especially
• P-selectin On endothelial cells
• platelets.
• E-selectin On endothelial cells.
• L-selectin On leukocytes,
• particularly lymphocytes.

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Firm adhesion

• It occurs after endothelial cells rolling
• leukocytes are activated by chemical mediators.
• When the leukocytes are activated, they express
  a new set of molecules, the integrins.
• Integrins bind to othe immunoglobulins
• ICAM. (Intercellular adhesion molecule)
• VCAM. (Vascular cell adhesion molecule)
• PE-CAM. (Platelet Endothelial cell adhesion
  molecule)
• MadCAM. (Mucosal addressin cell adhesion
  molecule)

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• 3.Emigration
• This means transmigration of leukocytes across
  the endothelium, occurs by the action of (
  PECAM-1)
• Then The leukocytes Pierce the basement membrane,
  and Migrate in the tissues toward a
  chemo-attractants at the source of injury, with
  the Formation of the inflammatory Exudate

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Emigration

• It is the escape of leukocytes from the blood
  to the peri-
• vascular tissues in search for the
  inflammatory site.

• After firm adhesion, the leukocytes insert large
• cytoplasmic extension pseudopodia into
  endothelial gaps.

• The gaps have been created by actions of
  histamine other chemical mediators as well as
  by the leukocytes themselves.

• Emigration occurs in the post capillary venule.
• The first to arrive are neutrophils. Then they
  are replaced by
• monocytes.
• In viral infections, lymphocytes are the first to
  arrive.
• In some hypersensitivity reactions, eosinophils
  are the first to
• arrive.

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• 4.chemotaxis.
• The directed movement of the leucocytes towards
  higher concentration of specific chemical
  substances is called chemotaxis.
• Those substances or factors that attract and
  direct the movement of leucocytes are called
  chemotactic factors.
• Neutrophils and some red cells also migrate
  through endothelial cells, by transcellular
  diapedesis

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Mechanisms of Chemotaxis

• Leukocytes have receptors on their membrane
• that bind the chemo-attractants.
• This results in a chain of biochemical reactions
• that causes increased intracellular calcium.
• The increased calcium results in the assembly of
• contractile elements responsible for cell
• movement towards the highest concentration of
  
• chemo-attractants.
• Movement is achieved by formation of a
• pseudopod that pulls the reminder of the cell
  in
• its direction.

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(2)
(1)
Pavementing
Margination
(3)
(4)

Chemotaxis

(5)
(6)
Phagocytosis

• Intracellular degradation.
• Synthesis of biochemical mediators.
• Extracellular release of Leukocyte
• Products

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Lots of cytoskeletal rearrangement to slip
through the endothelial wall.
The endotheliums inflamed!
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Lots of attractants- IL8, C5a, C3a, N-formyl
peptides!!!
Ig-Superfamily CAM
E-Selectin
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Margination,
Chemoattractants
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Mucin like ligans
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FORMATION OF INFLAMMATORY EXUDATES
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THE INFLAMMATORY EXUDATE It is an
inflammatory extravascular fluid And phagocytosis
MODE OF FORMATION OfINFLAMMATORY EXUDATE

• THE INCREASED VASCULAR PERMEABILITY
• That allows the escape of protein rich fluid and
  inflammatory cells into the extravascular space.

• (2)INCREASE IN THE INTRAVASCULAR HYDROTSATIC
• PRESSURE
• Resulting from the increased blood flow, a force
  that drives fluid outside the blood vessel.,

• (3) AN INCREASE IN THE COLLOIDAL OSMOTIC PRESSURE
  
• OF TISSUE PROTEIN
• Will draw fluid out in the tissue spaces. This
  third factor results from the break down of
  injured tissue protein plus the leaking plasma
  protein.

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COMPOSITION AND FUNCTION
Inflammatory Exudate Consists Of Two Parts
FLUIDE PART
CELLULAR PART
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• Cardinal Signs Of Inflammation
• Redness(rubor )
• Hotness (calor)
• Swelling.
• 4. Pain. (dolor)
• 5. Impairment of function.
• By understanding the vascular phenomena of
  inflammation, once can easily explain the
  mechanism of each of these signs.

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Character Of Inflammatory Exudate

• It is rich in protein,
• 4-8 gm, with high fibrinogen content.,,
• Its specific gravity is more than 1020.
• N.B. The fluid part formed in case of
  inflammatory lesions must be differentiated from
  that of transudate or oedema fluid which is
  characterized by

FLUID PART
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Differences Between Exudate And Transudate
EXUDATE TRANSUDATE
Fluid of inflammation High protein content 4 8 gm Specific gravity above 1018 Fibrinogen present . Clot on standing Contain inflamm. cell Fluid of oedema. Low protein content, below 1 gm Specific gravity below 1015 Fibrinogen not present Doet clot on standing No inflammatory cell
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  Inflammatory exudates   Transudate or edema fluid
 Specific gravity Specific gravity is more than 1020. Low specific gravity below 1020.
Content of protein. Protein, 4-8 gm, with high fibrinogen content. Lower content of protein.most of which is albumin.  
inflammatory cells Rich in acute inflammatory cells No inflammatory cells but contain few numbers of lymphocytes.
 characters Turbid and clot on standing due to presence of fibrinogen content. Clear and does not clot on standing due to absence of fibrinogen content.
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Functions Of Fluid Part

• Dilution of toxins.
• 2. Provide the inflammatory area with
• Antibodies (antitoxins, agglutinins,
• precipitins, opsonins).
• b) Components of the compliment system.
• c) Provides interferon, a non-specific
• antiviral agent.
• d) Brings therapeutic agents (antibiotics
• and anti-inflammatory), to the site of
  inflammation as well as nutrients.

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3. Its fibrinogen content is converted into a
fibrin network which is important in
providing a) A barrier to spread of organisms,
so localize the infection. b) Cement substances
uniting the injured tissues. c) It acts as a
network upon which the PNL, settled.
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CELLULAR PART (PHAGOCYTOSIS)

• In the early stages of acute inflammation,
• The PNL predominate,
• Followed after two to three days by MACROPHAGES
  derived from blood monocytes.
• Both types of cells are actively phagocytic due
  to their rich content of lysosome in their
  cytoplasm,
• Later still some lymphocytes and plasma cells
  appear in the cellular exudate.
• However, in acute allergic inflammation,
  eosinophils appear in significant numbers.

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The polymorph nuclear leukocyte(PNL)

• It is actively phagocytic (microphage),
• it ingests bacteria and digests them, aided
• by the process of opsonisation (coating
• bacterial surface with opsonin).
• The normal life span of the PNL is 3-4 days.
• After their death, they release their
• lysosomal enzymes which digest and
• Liquefy the damaged tissue and so form
• pus hence the dead PNL are called
• PUS CELLS

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THE MACROPHAGE

• Is A Larger Phagocytic Cell With A Pale
• Cytoplasm Rich In Lysosomes And Has A
• Large Vesicular Nucleus,
• It Is Derived From Either The Blood
• Monocytes Or The Tissue Histocytes.
• It Is Capable Of Ingesting
• Microorganisms And Larger Tissue
• Debris.
• It Helps To Clear And Clean The Area Of
  Inflammation For The Process Of Repair.

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PHAGOCYTOSIS
Is to engolf, kill to degrade foreign material,
most commonly bacteria.
(1) Recognition and attachment of the particle to
be ingested by the leukocyte (2) Engulfment
with subsequent formation of a phagocytic
vacuole and (3) killing or degradation of the
ingested material.
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PHAGOCYTOSIS OF BACTERIUM

• 1- It Recognition and attachment of bacteria
• Bacteria are recognized by the leukocytes
  receptor which is present on the bacterial wall
  acts as an antigen.
• Bacteria are opsonized by antibodies c3b
  fragments, which are recognized by specific
  receptors on the leukocytes surface.

• 2- Engulfment
• Small cytoplasmic extensions or pseudopods
  extended by the leukocyte.
• Pseudopods flow around the attached particle
  until it is engulfed.
• Cytoplasmic processes pinch together, meet fuse
  forming a phagosome

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• 3- Phagolysosome formation
• Fusion of lysosomal granules wit phagosome.
• Formation of phagolysosome.
• Killing of the bacteria in the phagolysosome.

Two bactericidal mechanisms are recognized in the
phagolysosome 1- Oxygen-dependent mechanisms
They are bactericidal. 2- Oxygen-independent
mechanisms As lysosome which hydrolized
bacterial wall glycoprotein leading to a powerful
bactericidal activity.
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• Cardinal Signs Of Inflammation
• Redness(rubor )
• Hotness (calor)
• Swelling.
• 4. Pain. (dolor)
• 5. Impairment of function.
• By understanding the vascular phenomena of
  inflammation, once can easily explain the
  mechanism of each of these signs.

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General Manifestation of Acute Inflammation

• 1. Fever Pyrexia due to pyrogen produced by
  PNL.
• 2. Leucocytosis provoked by the release of
  leucocytosis promoting factor from the injured
  tissues.
• 3. Degenerative changes affecting parenchymatous
  organs, heart, liver and kidney due to the
  circulation of absorbed toxins.

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Inflammation
Acute inflammation
Chronic Inflammation
Acute Non suppurative
Chronic Specific
Chronic Non-Specific
Acute suppurative
Catarrhal ,Serous fibrinous,Serofibrinous Member
nous ,Allergic and hemorrhgic
GRANULOMA
Localized
Diffuse
Abcsess Carbuncle
Cellulites
NON Infective Sarcoidosis Forgein body
Infective e.g T.B ,S,B
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TYPES OF ACUTE INFLAMMATION According to

• The Nature Of The Tissue.
• The Nature Of The Fluid.
• C) Character Of The Invading Organism.
• D) The Extend Of Tissue Damage,
• We Can Get One Of The Following

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I. SUPPURATIVE INFLAMMATION
Characterized by the formation of pus,
and according to the invading organism,
it can be either
Localized e.g.Abscess
Diffuse e.g. Cellulitis
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Suppurative Inflammation
Definition It is acute inflammation
characterized by by dense leucocytic infiltrate
and rapid liquefaction of the necrosed tissue
with the formation of pus. Aetiology
Pyogenic organism as staphylococci,streptococci,
gonococci,pneumococci and bacillus pyocyaneous

it can be either
Localized Or Diffuse.
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LOCALIZED SUPPURATIVE INFLAMMATION

• It is localized when the causative
  organism is the staphylococcus because it has a
  positive chemotactic property of PNL, to the area
  of inflammation causing digestion and
  liquefaction of the necrotic tissue forming pus.
• Staphylococci also produce coagulase enzyme
  which coagulate fibrin, localize, and prevent
  spread of infection.
• Common examples are the
• abscess, boil, and carbuncle

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ABSCESS

• It is localized suppurative inflammation
  resulting in a cavity that contains pus. It can
  be acute or chronic.
• Pathogenesis and mode of formation of acute
  abscess
• In the early stage, the introduction of pyogenic
  organism through the abrased skin or mucous
  membrane causes central area of necrosis
  surrounded by a zone of suppurative inflammation
  called the pyogenic membrane.
• 2. In the second step liquefaction of the
  peripheral part of the necrotic tissue occurs
  under the effect of proteolytic enzymes of PNL,
  resulting in the formation of an intermediate
  zone of pus between the central necrotic core and
  the pyogenic membrane.

Definition
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4.
The abscess extends and enlarges in size through
further necrosis and liquefaction of the
surrounding zone of inflamed tissue. The
liquefied necrotic tissue has a high osmotic
pressure that drags more fluid increasing the
tension in the abscess causing severe throbbing
pain and may lead to spontaneous rupture of the
abscess.
5.
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Pathognesis of abscess
Central zone of necrosis
Intermediate zone of pus
PNLs suarround Zone of necrosis
Central Area Of Necrosis
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• So The Abscess In Its Final Pattern Is
  Formed Of 3 Zones
• Central necrotic tissue (core).
• Intermediate zone of pus.
• 3. Outer pyogenic membrane.

1
2
3
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ABSCESS
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Whate Is The Character of Pus ?

• The pus is thick sticky alkaline fluid
• Does not coagulate on standing
• Formed of liquifactive necrotic tissue mixed
  with inflammatory fluid exudate including the
  causative organisms, dead and a life PNL

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1. If Evacuated(a) Healing by minimal
fibrosis. (b) Prevent
complications.
The Fate Of An Abscess

• 2. If Not Evacuated
• Becomes chronic.
• b) Undergoes dystrophic calcification.
• c) Risk of complications such as Ulcer, Sinus,
  Fistula, excessive scar and deformities.

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• Is discontinuity of surface epithelium of
  the skin or mucous membrane.
• Is a blind tract connecting the abscess cavity
  with the
• surface.
• It is lined by granulation tissue.
• An example of sinus is that associated with
  osteomyelitis
• it is open tract that
  connects two surfaces, two
• cavities, or surface and a cavity.
• Types or causes of fistula
• i) Congenital due to development abnormalities
  e.g. thyroglossal fistula.
• ii) Acquired due to trauma, inflammation or
  necrosis.

Ulcer
Sinus
Fistula
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FURUNCLE (BOIL)

• Small abscess related to a hair follicle or
  sebaceous gland caused by staphylococcus aureus.
• Common sites are face and back of the neck in
  males and axilla in females
• Multiple furuncles are called. Furunculosis

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CARBUNCLE
Definition

• A type of localized suppuration forming multiple
  communicating suppurative foci in the skin and
  subcutaneous fat discharging pus through several
  openings.
• Staphylococcus aureus. Diabetes mellitus is a
  common predisposing factor
• where the skin and subcutaneous tissue are
  thick and tough as the back of the neck, scalp
  and buttocks.

Cause
Sites Areas
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• Pathology
• Multiple communicating suppurative foci in the
  subcutaneous fat opening on the surface at
  multiple points particularly at the base of the
  hair follicles.
• Each suppurative focus develops in the same way
  as an abscess.
• The development of multiple Suppurative foci in
  carbuncle is due to the presence of dense fibrous
  septa extending from the deep fascia up to the
  dermis dividing the area into several

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CARBUNCLE
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CARBUNCLE
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• Boil (furuncle) is a small abscess related to
  hair follicle, sebaceous or sweat glands.
  Multiple boils are called frunculosis.
• Carbuncle
• is a multilocular abscess with multiple openings,
  occurs in areas where the skin and subcutaneous
  tissues are thick and inelastic as the back of
  the neck, scalp or buttock.
• In such areas, there are dense interlacing
  longitudinal and transverse bundles of fibrous
  tissue enclosing fat and inflammation spreads
  along these bundles, so pus is formed in multiple
  loculi.
• Usually met with in diabetic patients having low
  resistance to pyogenic infection.

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II. Diffuse suppurative inflammation
(cellulitis)
Causative pyogenic organism Is
streptococcuspyogenous.
These organisms secrete different enzymes
(spreading factors) ?fibrinolysin that digest
fibrin ? hyaluronidase which digest and
liquefy hyaluronic acid of the ground
substances.
So infection spreads rapidly in the tissue
spaces. Necrosis is more extensive than in case
of an abscess. The pus formed is thin in
consistency and is blood stained (sanguineous).
It is more liable to be complicated by
lymphangitis and lymphadenitis and spread by the
blood causing septicemia or pyaemia.
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