Acute Inflammation

1. Item-05 and 06
Inflammation
Acute Inflammation
Dr. A K M Maruf Raza
Associate Professor of Pathology
Based on Robbins and Cotran
9th edition

2. Inflammation
 Inflammation is a protective response essential
for survival.
 It serves to protect the host from both the
initial cause of cell injury (microbes, toxins)
and the consequences of such injury.
 The mediators of defense against infection
include phagocytic leukocytes (nutrophils,
macrophages), antibodies and complement
proteins.
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3. Inflammation
 The process of inflammation delivers these
cells and proteins to damaged or necrotic
tissues and microbes.
 Activates them to get rid of the harmful or
unwanted substances.
 Without inflammation, infections would go
unchecked, wounds would never heal, and
injured tissues might remain permanent
festering sores. 3

4. Sequential steps of inflammatory
reaction
The steps of the inflammatory response can be
remembered as the five R:
(1) recognition of the injurious agent
(2) recruitment of leukocytes
(3) removal of the injurious agent
(4) regulation (control) of the response
(5) resolution (repair)
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5. Inflammation; Definition:
Inflammation is a response of:
i. vascularized tissues to infections and
damaged tissues
ii. that brings cells and molecules of host
defense from the circulation to the sites
where they are needed
iii. in order to eliminate the offending agents.
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6. Types of inflammation
i. Acute inflammation
ii. Chronic inflammation
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7. Types of inflammation
Acute inflammation:
The initial, rapid response to infections and tissue
damage is called acute inflammation.
i. rapid in onset (seconds or minutes)
ii. short duration, lasting for minutes to
several hours or a few days.
iii. predominant cell is neutrophil.
iv. characteristic features are exudation of
fluid and plasma protein and
emigration of neutrophils.
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8. Types of inflammation
Chronic inflammation:
If acute inflammation fails to clear the offending
agent, it may progress to a long period phase
is called chronic inflammation.
i. is of longer duration.
ii. associated with presence of lymphocyte
and macrophages.
iii. and proliferation of blood vessels and
deposition of connective tissue (fibrosis)
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9. Acute inflammation VS Chronic inflammation
Feature Acute Chronic
Onset Fast: minutes to
hours
Slow: weeks to
days
Cellular
infiltrate
Mainly
neutrophils
Lymphocytes,
Monocytes/
macrophages
Tissue injury
and fibrosis
Usually mild and
self-limited
Often severe and
progressive
Local and
systemic signs
Prominent Less 9

10. Advantage of inflammation
 Inflammation usually functions in a beneficial
manner.
 It serves to destroy, dilute or wall off the
injurious agent.
 Remove necrotic debris and other exudates.
 Prepare the remaining tissue framework for
tissue repair.
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11. Disadvantage of inflammation
Often accompanied by local tissue damage.
May underlie some life threatening
hypersensitivity reactions to insect bites,
drugs and toxins.
Sometimes associated with common
chronic diseases such as rheumatoid
arthritis, atherosclerosis, crohn disease.
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12. Cardinal signs of inflammation
 Celsus, first listed the four cardinal signs:
1. Rubor- redness
2.Tumor- swelling
3. Calor- heat
4. Dolor- pain
 Rudolf Virchow in the 19th century added:
5. loss of function (Functio laesa).
So there are five cardinal signs of inflammation.
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13. Causes of Inflammation
Inflammatory reactions may be triggered by a variety
of stimuli:
i. Infections (bacterial, viral, fungal,
parasitic) and microbial toxins are the
most common and medically important
causes of inflammation.
ii. Tissue necrosis elicits inflammation in
myocardial infarction, trauma, physical
and chemical injury.
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14. Causes of Inflammation
iii. Foreign bodies (splinters, sutures).
Even endogenous substances in excess
amount such as urate crystals (gout).
iv. Immune reactions (hypersensitivity):
 are reactions in which the protective immune
system damages own tissues.
 Immune responses may be directed against
self antigens, causing autoimmune diseases,
or may be against environmental substances,
as in allergies. 14

15. Acute Inflammation
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16. Acute Inflammation
Acute inflammation is the inflammation of
rapid in onset, has relatively short duration
characterized by exudation of fluid and
plasma protein and emigration of
leukocytes predominantly neutrophils.
Example: Acute tonsillitis, Acute appendicitis,
Acute cholecystitis, Abscess, Boil.
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17. Acute inflammation: Terminology
Exudate: An exudate is an inflammatory
extravascular fluid that has high protein
concentration, cellular debris, and a specific
gravity above 1.020.
Transudate: Is a fluid with low protein
content, and a specific gravity below 1.020
caused by increased hydrostatic pressure
or reduced plasma osmotic pressure.
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18. Exudate VS Transudate
Exudate
Inflammatory fluid
Total protein more than 30gm/L
Protein as plasma
Fibrinogen present so clot is formed
Plenty of inflammatory cells,
neutrophils or lymphocytes
Specific gravity more than 1.020
Transudate
Non inflammatory fluid
Less than 10gm/L
Practically all albumin
Not present, no clot
A few cells may be present
Specific gravity less than 1.012

19. Three components of the acute
inflammation
1. Dilation of the vessels leading to an increase
in blood flow,
2. Increased permeability of the
microvasculature causing plasma proteins and
leukocytes to leave the circulation,
3. Emigration of the leukocytes from the
microcirculation, accumulation and activation
to eliminate the offending agent. 19

20. Reactions of Blood Vessels in Acute
Inflammation
The vascular reactions of acute inflammation
consist of:
i. changes in the flow of blood and the
permeability of vessels
ii. Maximize the movement of plasma
proteins and leukocytes out of the
circulation and into the site of
infection or injury.
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21. Vescular reaction in Acute
Inflammation
1. Changes in Vascular Flow and Caliber.
2. Increased Vascular Permeability.
(Vascular Leakage)
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22. Changes in Vascular Flow and Caliber
 Vasodilation is induced by histamine on
vascular smooth muscle causing increased
blood flow, causing heat and redness at the
site of inflammation.
 Vasodilation is quickly followed by increased
permeability of the microvasculature with the
outpouring of protein-rich fluid into the
extravascular tissues.
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23. Changes in Vascular Flow and Caliber
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24. Increased Vascular Permeability
(Vascular Leakage)
Mechanisms for increased vascular permeability:
i. Contraction of endothelial cells resulting in
increased interendothelial spaces (most common
mechanism).
ii. Endothelial injury, resulting in endothelial cell
necrosis and detachment.
iii. Transcytosis, transport of fluids and proteins
through the endothelial cell involving intracellular
channels.
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25. Increased Vascular Permeability
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26. Leukocyte Recruitment to Sites of
Inflammation
 The changes in blood flow and vascular
permeability are quickly followed by an influx
of leukocytes into the tissue.
 These leukocytes (neutrophils, macrophages)
ingest and destroy bacteria and other
microbes, as well as necrotic tissue and
foreign substances.
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27. Leukocyte recruitment to sites of
inflammation
The journey of leukocytes from the vessel lumen to the
tissue is a multistep process:
1. In the lumen of blood vessel: margination,
rolling, and adhesion to endothelium.
2. Migration across the endothelium and vessel
wall.
3. Exiting from the vessel migration in the
tissues towards injurious agent (chemotaxis).27

28. margination, rolling, and adhesion to
endothelium
 Vascular endothelium in normal state does not
bind circulating cells. In inflammation, the
endothelium is activated and can bind
leukocytes.
 In inflammation hemodynamic conditions
changes and white cells comes along the
endothelial surface.
 This process of leukocyte redistribution is
called margination.
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29. In the lumen: margination, rolling, and
adhesion to endothelium
 The leukocytes adhere transiently to the
endothelium, detach and bind again which is
called rolling.
 This rolling is mediated by a family of proteins
called selectins and intigrins.
 The next step is migration of the leukocytes
through the endothelium called transmigration
or diapedesis.
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30. margination,rolling and diapedesis
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31. Chemotaxis of Leukocytes
 After exiting the circulation, leukocytes move
in the tissues toward the site of injury by a
process called chemotaxis.
 Chemotaxis is defined as locomotion along a
chemical gradient.
 The chemical gradient (chemoattractants) can
be both exogenous and endogenous
substances.
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32. Chemotaxis
The Chemoattractants causing chemotaxis are:
i. Exogenous: bacterial protein, bacterial
cell membrane lipids.
ii. Endogenous: Cytokines IL8, complement
system C5a, Leukotriene-B4.
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33. Phagocytosis and Clearance
of the Offending Agent
 Phagocytosis, or “cell eating” is the process
by which a cell engulfs a particle and digests it.
 Destruction of microbes is caused by free
radicals (ROS, NO) generated in activated
leukocytes and lysosomal enzymes.
 There are three steps of phagocytosis.
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34. Phagocytosis
i. Recognition and attachment of the particle to
be ingested by the leukocytes.
ii. Engulfment of the particle with subsequent
formation of a phagocytic vacuole
(phagosome).
iii. Killing or Degradation of the ingested
material by free radicals (ROS, NO) generated
in activated leukocytes and lysosomal
enzymes (Phagolysosome).
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35. Phagocytosis
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36. Mediators of inflammation
The mediators are the substances that
initiate and regulate inflammatory reactions.
Active mediators are produced only in
response to various stimuli.
Most of the mediators are short-lived.
One mediator can stimulate the release of
other mediators. 36

37. Mediators of inflammation
Mediators are either secreted by cells or generated
from plasma proteins.
1. Cellular/ Cell derived mediators :
a) Preformed mediators: Histamine,
Serotonin, lysosomal enzymes.
b) Newly synthesized: Prostaglandins,
Leukotrienes, Cytokines.
2. Plasma derived mediators:
Complement: C3a, C5a, C3b, C5b-9.
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38. Role of Mediators in different Reactions of
inflammation
Reaction of inflammation Principal Mediators
Vasodilation Histamin, Prostaglandins
Increased vascular
permiability
Histamin, Serotinin
Leukotriens C4,D4,E4
Chemotaxis, leukocyte
recruitment and activation
TNF, IL-1
Leukotriene B4
Fever IL-1,TNF
Prostaglandins
Pain Prostaglandin
Bradykinin

39. Role of mediator in inflammation
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40. Morphologic Pattern of Acute
Inflammation
 The morphologic hallmarks of acute
inflammatory reactions are dilation of small
blood vessels and accumulation of leukocytes
and fluid in the extravascular tissue.
 Special morphologic patterns are often provide
valuable clues about the underlying cause.
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41. Morphologic Pattern of Acute
Inflammation
1. Purulent (Suppurative) Inflammation
(Abscess):
 It is characterized by production of large
amount of pus consisting of dead or dying
neutrophils, necrotic cells and tissue debris.
 It usually caused by pyogenic bacteria.
 Abscess is the localized collection of purulent
inflammatory tissue (Pus).
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42. Morphologic Patterns of Acute
Inflammation
2. Serous inflammation: Characterized by
accumulation of serous fluid. Skin blister,
Pleural and pericardial effusion.
3. Fibrinous inflammation: Accumulation of fibrin
rich fluid in the extracellular space. Inflammation
in the lining of body cavities (meninges,
pericardium and pleura).
4. Ulcer: An ulcer is a local defect or excavation of
the surface of an organ or tissue produced by
the shedding of inflamed necrotic tissue.
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43. Outcome of acute Inflammation
1. Complete resolution.
2. Healing by connective tissue replacement
(scarring or fibrosis).
3. Progression to chronic inflammation
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