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Chapter13 and 14 Hei
Chapter13 and 14 Hei
ZUHAIRA SAHID
SUBTOPIC
• The role of inflammation in health and disease
• The role of endogenous agents
• Sequelae of inflammation
• Acute and chronic inflammation
Characteristics
Influencing factors
Similarities and differences
TOPIC OUTCOMES
At the end of this lecture, students are able to :
1. Describe orally the signs of inflammation
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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 necrotic cells and
tissues.
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Causes of inflammation;
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Involves 2 basic
processes (overlapping):
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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
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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 (PMN)
as inflammatory cells
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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
macrophages)
I) ACUTE INFLAMMATION
The changes can be conveniently described
under:
(i) Vascular events
(ii) Cellular events
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(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
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THE SEQUENCE OF THESE CHANGES:
Transient vasoconstriction
Slowing or stasis
Leucocytic margination
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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 18
Triple response
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(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)
NO
OEDEMA OEDEMA
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EDEMA
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MECHANISMS OF INCREASED
VASCULAR PERMEABILITY
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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 only
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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.
Monocytes
Macrophages
(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;
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
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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 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 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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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 cholecystitis
iii) Starting de novo – infection with organisms
of low pathogenecity (chronic from the
beginning) eg: TB 41
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
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SYSTEMIC EFFECTS OF CHRONIC INFLAMMATION
3. Leucocytosis - general
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INJURY
(e.g; by M. tuberculosis, talc
GRANULOMA
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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)
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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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2.4: MORPHOLOGIC PATTERNS OF ACUTE
& CHRONIC INFLAMMATION
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SEROUS INFLAMMATION - EFFUSION
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SEROUS INFLAMMATION - EFFUSION
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Fibrinous inflammation; the formation of
fibrin is striking e.g. in acute pleurisy.
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FIBRINOUS INFLAMMATION
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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 - 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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REGENERATION, HEALING AND REPAIR
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.
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REGENERATION
Maintain proper structure of tissue
The replacement of cell can happen in two
ways:
by regeneration: the necrotic cells are
tissue.
Most organs will heal using a mixture of both
mechanism.
In order for an injury to be healed by
regeneration, the cell type that was
destroyed must be able to replicate.
Most cells have this ability, although it is
believed that cardiac muscle cells and
neurons are two important exceptions.
Cells also need a collagen framework along
which to grow.
Alongside, most cells there is either a
basement membrane or a collagenous
network made by fibroblasts that will guide
the cells growth.
Proliferation of original cell occur from the
margin of injury.
Since ischaemia and most toxins do not
destroy collagen, it will continue to exist
even when the cells around it are dead.
Local factors that interfere with the
healing process such as:
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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 GRANULATION
2 main processes:
i. Angiogenesis (neovascularisation)
formation of new blood vessels
ii. 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
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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 infection
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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 SCAR
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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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THANK YOU
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