INFLAMMATION
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2 Inflammation
Inflammation is a response of vascularized
tissues to
infections and tissue damage that brings cells and
molecules of host defense from the circulation to
the sites where they are needed, to eliminate the
offend in agents
Aims:
1.Remove cause (microbe) and consequence of cell
injury (necrotic cell)
2.Inactivate toxins
3.Repair and heal the injured site
sequential steps Of Inflammation
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The offending agent, which is located in extravascular tissues, is
recognized by host cells and molecules.
Leukocytes and plasma proteins are recruited from the
circulation to the site where the offending agent is located.
The leukocytes and proteins are activated and work together to
destroy and eliminate the offending substance.
The reaction is controlled and terminated.
The damaged tissue is repaired.
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5 Types of Inflammation
Acute Chronic
Early and fast response to an injury Delay and progressive response
1st line of defense against injury to an injury
Start in a day and remain long
Start within minute to hour
Mainly involve macrophages
Remain for several hours or days
and lymphocytes
Mainly involve neutrophils
May cause failure of an organ
Mild tissue injury
Less local and systemic signs
Prominent local and systemic signs
Causes of Inflammation
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• Infections (bacterial, viral, fungal, parasitic) and microbial
toxins
• Tissue necrosis elicits inflammation regardless of the cause of
cell death,
Foreign bodies (splinters, dirt, sutures) may elicit inflammation
by themselves or because they cause traumatic tissue injury or
carry microbes.
Immune reactions (hypersensitivity) are reactions in which the
normally protective immune system damages the individual’s
own tissues.
The injurious immune responses may be directed against self
antigens, causing autoimmune diseases, or may be inappropriate
reactions against environmental substances.
7 Characteristics of Acute
Inflammation
1. Rapid onset
2. Short duration (goal achieved)
3. Formation of exudate (protein rich fluid)
4. WBC recruitment (neutrophils)
5. Predominant signs and symptoms
6. Start repairing
Cardinal Signs
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The external manifestations of
inflammation, called its cardinal
signs
1. Robor – redness
2. Color – heat
3. Dolor – pain
4. Tumor – swelling
5. Functio-laesa – loss of function
Historical background of inflammation
and cardinal sign of inflammation
• The first four of these were describe more than 2000 years ago by
a Roman encyclopedist name Celsus, who wrote the then-famous
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text De Medicina, and the fifth was added in the late 19th century
by Rudolf Virchow, known as the “father of modern pathology.”
• These manifestations occur as consequences of the vascular
changes and leukocyte recruitment and activation
10 Components of Acute
inflammation
(1) dilation of small vessels, leading to an increase in blood
flow,
(2) increased permeability of the microvasculature, enabling
plasma proteins and leukocytes to leave the circulation,
(3) emigration of the leukocytes from the microcirculation,
their accumulation in the focus of injury, and their activation
to eliminate the offending agent
Changes in Vascular Flow and
11 Caliber
• Vasodilation is induced by the action of several mediators, notably histamine, on
vascular smooth muscle.
The result is increased blood flow, which is the cause of heat and redness
(erythema) at the site of inflammation.
• Vasodilation is quickly followed by increased permeability of the
microvasculature, with the outpouring of protein-rich fluid (an exudate) into the
extravascular tissues.
• The loss of fluid and increased vessel diameter lead to slower blood flow,
concentration of red cells in small vessels, and increased viscosity of the blood.
These changes result in stasis of blood flow, puffiness of small vessels jammed
with slowly moving red cells,
seen histologically as vascular congestion and externally as localized redness
(erythema) of the involved tissue.
12 Changes in Vascular Flow and
Caliber
• As stasis develops, blood leukocytes, principally
neutrophils, accumulate along the vascular endothelium.
At the same time endothelial cells are activated by mediators
produced at sites of infection and tissue damage, and express
increased levels of adhesion molecules.
Leukocytes then adhere to the endothelium, and soon
afterward they migrate through the vascular wall into the
interstitial tissue.
Lymphatic vessels and lymph nodes also are involved in
inflammation, and often show redness and swelling.
Increased Vascular Permeability (Vascular Leakage)
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Retraction of endothelial cells resulting in opening of interendothelial spaces is the
most common mechanism of vascular leakage.
It is elicited by histamine, bradykinin, leukotrienes, and other chemical mediators.
The main sites for this rapid increase in vascular permeability are postcapillary venules.
• Endothelial injury, resulting in endothelial cell necrosis and detachment.
Direct damage to the endothelium is encountered in severe injuries, for example, in
burns, or is induced by the actions of microbes and microbial toxins that target
endothelial cells.
Neutrophils that adhere to the endothelium during inflammation may also injure the
endothelial cells and thus amplify the reaction.
• Increased transport of fluids and proteins, called transcytosis,
This process may involve intracellular channels that open in response to certain factors,
such as vascular endothelial growth factor (VEGF), that promote vascular leakage.
Leukocyte Recruitment to Sites of
Inflammation
14 The most important leukocytes in typical inflammatory reactions are the ones
capable of phagocytosis, namely, neutrophils and macrophages.
Neutrophils use cytoskeletal rearrangements and enzyme assembly to stand rapid,
transient responses, whereas macrophages, being long-lived.
These leukocytes ingest and destroy bacteria and other microbes, as well as necrotic
tissue and foreign substances.
Macrophages also produce growth factors that aid in repair.
The journey of leukocytes from the vessel lumen to the tissue is a multistep
process that is mediated and controlled by adhesion molecules and cytokines.
Leukocytes normally flow rapidly in the blood, and in inflammation, they have to be
stopped and then brought to the offending agent or the site of tissue damage, outside
the vessels.
15 Vascular Changes
s
16 Vascular Changes
Leukocyte Adhesion to
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Endothelium
Margination
RBC being smaller, move faster in center than larger
WBC (periphery)
In stasis, RBC clump together and form large body
Clump size > WBC and will displace it toward
endothelium
Rolling
Displaced WBC roll over endothelium by attach and
detach mechanism, until adhere transiently with
endothelium
Loose bond is formed by adhesion molecules present at
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19 Leukocyte Adhesion to
Endothelium
Firm adhesion
After transient adhesion, cytokine express their ligand and integrine
(glycoprotein) and get activated
Ligands Integrines
VLA4 – very late activation antigen VCAM1 – vascular cell adhesion
molecule
LFA1 – lymphocyte function associated antigenICAM1 – Intracellular adhesion molecule
20 Leukocyte Migration Through
Endothelium
Emigration
WBC attached to endothelium leave blood and migrate to the site of
inflammation, driven by PECAM-1 (platelet endothelial cell adhesion
molecule)
Intercellular spaces form pseudopodium which expand the space and
allow WBC-EC complex to come out into ECS
21 Chemotaxis of Leukocytes
At site of inflammation chemo attractants are
presents:
Exogenous – microbial products
Endogenous – cytokines (IL-8), complement protein
(C5a)
These attract WBC by binding with its G-protein
coupled receptors and rely signals – Initiate
reactions in actin
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Chemotaxis of Leukocytes
Phagocytosis Termination
• All mediator inactivate
1. Recognition due to short ½ half lives
2. Attachment
3. Engulfment • Neutrophil start
4. Killing apoptosis
• Macrophages release
anti-inflammatory
cytokine – TGF-B,IL-10,
stop release of TNF-a
23 Morphologic Patterns
1. Serous Inflammation: exudation of cells poor fluid into spaces
created by injury or body cavities – effusion
2. Fibrinous Inflammation: exudation of fibrin rich fluid, may
convert into fibroblast and form a scar
3. Purulent/Suppurative Inflammation (Abscess): exudation of
neutrophil and debris rich edematous fluid – pus
4. Ulcers: local excavation of tissue surface due to sloughing of
inflamed necrotic tissue
24 Outcomes of Acute
Inflammation
1. Complete elimination
of offending agent with
restoration of site
2. Healing by connective
tissue replacement
3. Progression to chronic
inflammation
25 Chronic Inflammation
Prolong response of body to persistent injurious stimulus –
weeks to months
Inflammation, tissue injury and repair coexist
May follow acute inflammation or not –
Often progressive without any signs of acute reaction
26 Characteristics of Chronic
Inflammation
Unlike acute inflammation – edema, vascular changes and
predominant neutrophil infiltration, it involve:
1. Infiltration of mononuclear cells – macrophages, lymphocytes
and plasma cells
• Sometime mast cells, eosinophil and neutrophils
2. Tissue destruction – persistent offending agent or inflammatory
cells
3. Healing – connective tissue replacement of damaged tissue
(fibrosis) and angiogenesis
27 Macrophages
Dominant chronic inflammatory cells, life span of
months to years
Secretion – cytokines and growth Phagocytosis – filter particulate
factors – act on various cells: matter, microbes and damaged cells
• Destroy invaders and tissues • Circulation – monocyte
• Activate T-lymphocyte – antigen • Transfer after 1 day to specific
presentation organ
• Receive signal from T-cells 1. Liver – Kupffer cells
• Repairing – interleukin 2. Spleen, lymph nodes – histiocytes
3. CNS – microglia
• Phagocytosis
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THANK
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