1. Acute inflammation is rapid in onset and short in duration, characterized by fluid and protein exudation and neutrophil accumulation. Chronic inflammation is slower in onset and longer lasting, characterized by mononuclear cell infiltration, ongoing tissue destruction, and attempts at repair through fibrosis. 2. The key features of acute inflammation are vasodilation, increased vascular permeability, and recruitment of leukocytes from the blood vessels to the site of injury. Chronic inflammation features mononuclear cell infiltration, persistent tissue damage, and attempts to repair through fibrosis and angiogenesis. 3. Granulomatous inflammation is a pattern of chronic inflammation seen with certain infections, featuring focal collections of activated macrophages that develop an epithelial-like appearance known

1. CHAPTER -II
• Contents
1. Inflammation
I. Acute
II. Chronic
2. Wound healing
3. Defect immune response
4. Hypersesitivity

2. INFLAMMATION
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3. INFLAMMATION
Introduction: Allows inflammatory cells, plasma proteins (e.g., complement), and fluid to exit blood vessels and enter the interstitial
space -
• “Inflame” – to set fire.
• Inflammation is “dynamic response of
vascularised tissue to injury.”
•Is a protective response.
•Serves to bring defense & healing
mechanisms to the site of injury.
3
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4. General Features of Inflammation
• Inflammation is fundamentally a protective host
response, the ultimate goal of which is:
1. to rid the organism of both the initial cause of cell
injury (e.g., microbes, toxins) and the consequences
of such injury (e.g., necrotic cells and tissues).
2. Repair the tissue injured
• Without inflammation, infections would go
unchecked, wounds would never heal, and injured
organs might remain permanent festering sores.
4
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5. Inflammation cont…
• Many tissues and cells are involved in these
reactions, including the fluid and proteins of:
 plasma,
 circulating cells,
 blood vessels, and
 cellular and extracellular constituents of connective
tissue.
• The circulating cells include neutrophils,
monocytes, eosinophils, lymphocytes, basophils,
and platelets.
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7. Steps of the inflammatory response
• The steps of the inflammatory response can be
remembered as the five Rs:
(1) Recognition of the injurious agent,
(2) Recruitment of leukocytes,
(3) Removal of the agent,
(4) Regulation (control) of the response, and
(5) Resolution (repair).
• The outcome of acute inflammation is either:
 elimination of the noxious stimulus followed by decline of
the reaction and repair of the damaged tissue, or
 persistent injury resulting in chronic inflammation.
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8. TYPES OF INFLAMMATION
• ACUTE INFLAMMATION
• CHRONIC INFLAMMATION
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9. Acute inflammation
• Acute inflammation is rapid in onset and of short
duration, lasting from a few minutes to as long as a
few days.
• characterized by fluid and plasma protein
exudation and a predominantly neutrophilic
leukocyte accumulation.
• is a rapid response to an injurious agent that serves
to deliver mediators of host defense—leukocytes
and plasma proteins—to the site of injury.
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10. CARDINAL SIGNS OF INFLAMMATION
• Rubor : Redness
• CALOR : WARM
• DOLOR : PAIN -NERVE, CHEMICAL.
• TUMOR: SWELLING – EXUDATION
• LOSS OF FUNCTION:
10
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11. Heat Redness Swelling Pain Loss Of Func.
The 5 Cardinal Signs of
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12. STIMULI FOR ACUTE INFLAMMATION
• Infections (bacterial, viral, parasitic) and
microbial toxins
• Trauma (blunt and penetrating)
• Physical and chemical agents (thermal injury,
e.g., burns or frostbite; irradiation; some
environmental chemicals)
• Tissue necrosis (from any cause)
• Foreign bodies (splinters, dirt, sutures)
• Immune reactions (also called
hypersensitivity reactions).
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13. Components of acute inflammation
• The inflammatory response consists of two
main components:
1. a vascular reaction (vasodilation and
↑vascular permeability)
2. a cellular reaction (emigration of the
leukocytes )
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14. Vascular Changes
• Vasodilation: is one of the earliest manifestations
of acute inflammation; sometimes, it follows a
transient vasoconstriction of arterioles, lasting a
few seconds.
• Vasodilation first involves the arterioles and then
results in opening of new capillary beds in the
area.
• Thus comes about increased blood flow, which is
the cause of the heat and the redness.
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15. Changes in Vascular Flow and Caliber…
• Vasodilation is quickly followed by increased permeability
of the microvasculature, with the outpouring of protein-rich
fluid into the extra vascular tissues. (role of histamin & other
kinins)
• The loss of fluid results in concentration of red cells in small
vessels and increased viscosity of the blood, reflected by the
presence of dilated small vessels packed with red cells and
slower blood flow, a condition termed stasis.
• As stasis develops, leukocytes, principally neutrophils,
accumulate along the vascular endothelium.
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17. Mechanism of Inflammation
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18. CELLULAR EVENTS
• The sequence of events in the journey of
leukocytes from the vessel lumen to the interstitial
tissue, called extravasation, can be divided into the
following steps:
1. In the lumen: margination, rolling adhesion to
endothelium
2. More stable adhesion to endothelium.
3. Transmigration across the endothelium (also
called diapedesis)
4. Migration in interstitial tissues toward a
chemotactic stimulus.
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20. Neutrophil Margination
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21. Chemotaxis
• After extravasation, leukocytes emigrate in tissues
toward the site of injury by a process called
chemotaxis, defined most simply as locomotion
oriented along a chemical gradient.
• All granulocytes, monocytes and, to a lesser extent,
lymphocytes respond to chemotactic stimuli with varying
rates of speed.
• Both exogenous and endogenous substances can act as
chemo-attractants.
• The most common exogenous agents are bacterial
products.
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22. Outcomes of Acute Inflammation
• Acute inflammation may have one of three
outcomes :
1. Complete resolution.
2. Healing by connective tissue replacement
(fibrosis).
3. Progression of the tissue response to
chronic inflammation.
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23. PATHOLOGY
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24. Inflammation Outcome
Acute
Inflammation
Resolution
Chronic
Inflammation
Abscess
Sinus
Fistula
Fibrosis/Scar
Ulcer
Injury
Fungus
Virus
Cancers
T.B. etc.
PATHOLOGY
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25. Morphologic types
• Acute:
Exudative Inflammation: excess fluid. Lung TB.
Suppuration/Purulent – Bacterial - neutrophils
Fibrinous – pneumonia – fibrin
Serous – excess clear fluid – Heart, lung
Haemorrhagic – b.v. damage
• Chronic inflammation: with healing.
Grannulomatous – clusters of epitheloid cells e.g. TB,
Fungus, Foreign body.
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26. Fibrinous pericarditis. A, Deposits of fibrin on the
pericardium. B, A pink meshwork of fibrin exudate (F) overlies
the pericardial surface (P).
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27. Serous inflammation. Low-power view of a cross-section of a
skin blister showing the epidermis separated from the dermis
by a focal collection of serous effusion
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28. Purulent lungs
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29. Pneumonia
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30. Chronic Inflammation
• Chronic inflammation may be more
insidious, is of longer duration (days
to years), and is typified by influx of
lymphocytes and macrophages with
associated :
vascular proliferation and
 fibrosis (scarring).
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31. Chronic Inflammation…
• Although difficult to define precisely:
chronic inflammation is considered to be
inflammation of prolonged duration (weeks or
months) in which :
active inflammation,
tissue destruction, and
 attempts at repair are proceeding simultaneously.
• Although it may follow acute inflammation,
chronic inflammation frequently begins
insidiously, as:
 a low-grade,
smoldering, often asymptomatic response.
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32. Chronic
Inflammation:
Lung
Abscess
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33. CAUSES OF CHRONIC INFLAMMATION
• Chronic inflammation arises in the following settings:
1. Persistent infections by certain microorganisms, such as
tubercle bacilli, Treponema pallidum (the causative
organism of syphilis), and certain viruses, fungi, and
parasites.
• These organisms are of low toxicity and evoke an
immune reaction called delayed type hypersensitivity.
• The inflammatory response sometimes takes a specific
pattern called a granulomatous reaction
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34. CAUSES OF CHRONIC INFLAMMATION…
2. Prolonged exposure to potentially toxic
agents, either exogenous or endogenous.
• Atherosclerosis - is thought to be a
chronic inflammatory process .
3. Autoimmunity
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35. MORPHOLOGIC FEATURES
• In contrast to acute inflammation, which is manifested by
vascular changes, edema, and predominantly neutrophilic
infiltration, chronic inflammation is characterized by:
• Infiltration with mononuclear cells, which include
macrophages, lymphocytes, and plasma cells.
• Tissue destruction, induced by the persistent
offending agent or by the inflammatory cells.
• Attempts at healing by connective tissue replacement
of damaged tissue, accomplished by proliferation of small
blood vessels (angiogenesis) and, in particular, fibrosis.
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36. Chronic inflammation in the lung, showing the characteristic histologic
features: collection of chronic inflammatory cells (asterisk), destruction of
parenchyma (normal alveoli are replaced by spaces lined by cuboidal
epithelium, arrowheads), and replacement by connective tissue (fibrosis,
arrows).
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37. Acute inflammation
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38. Types of chronic inflammation
 Non-specific
•Characterized by diffuse infiltration
with macrophages plasma cells and
lymphocytes
E.g. chronic cholecystitis(inflammation
of gallbladder)
 Specific (granulomateous)
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39. GRANULOMATOUS INFLAMMATION
• Granulomatous inflammation is a
distinctive pattern of chronic
inflammatory reaction characterized:
• by focal accumulations of activated
macrophages, which often develop
an epithelial-like (epithelioid)
appearance.
• eg. tb ,leprosy syphilis etc.
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40. Granuloma:
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41. TB caseuos necrosis
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42. ACUTE VS CHRONIC
ACUTE
• Flush, Flare & Weal
• Acute inflammatory
cells - Neutrophils
• Vascular damage
• More exudation
• Little or no fibrosis
• Less tissue damage
CHRONIC
• Little signs - Fibrosis
• Chronic inflammatory
cells – Lymphocytes
• Neo-vascularisation
• No/less exudation
• Prominent fibrosis
• More tissue damage
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43. SYSTEMIC EFFECTS OF INFLAMMATION
• Fever, characterized by an elevation of body temperature, usually by
1° to 4°C, is one of the most prominent manifestations of the acute
phase response, especially when inflammation is associated with
infection.
• Acute-phase proteins are plasma proteins, mostly synthesized in the
liver, whose plasma concentrations may increase several hundred-
fold as part of the response to inflammatory stimuli.
• Leukocytosis is a common feature of inflammatory reactions,
especially those induced by bacterial infection
• leucopenia (occasional)
• Wt loss
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44. CONSEQUENCES OF INFLAMMATION
• To summarize the clinical and pathological
consequences of too much or too little
inflammation.
• Defective inflammation typically results in
increased susceptibility to infections and delayed
healing of wounds and tissue damage.
(e.g. HIV, congenital immunodeficiency,
Medications) PATHOLOGY
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45. …CONSEQUENCES OF INFLAMMATION
• Excessive inflammation is the basis of many categories of
human disease.
• allergies, in which individuals mount unregulated
immune responses against commonly encountered
environmental antigens,
• autoimmune diseases, in which immune responses
develop against normally tolerated self-antigens.
• Abscess formation
–Fistula
–Sinus
–Sepsis
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48. WOUND HEALING
• Tissue Renewal and Repair:
• Regeneration, Healing, and Fibrosis
• The body's ability to replace injured or dead
cells and to repair tissues after inflammation is
critical to survival.
• When injurious agents damage cells and
tissues, the host responds by setting in motion
a series of events that serve to eliminate these
agents, contain the damage, and prepare the
surviving cells for replication.
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49. Wound healing…
•The repair of tissue damage caused by surgical
resection, wounds, and diverse types of chronic
injury can be broadly separated into two
processes:
1.Regeneration and
2.Healing (repair ,scar formation).
•Regeneration results in restitution of lost
tissues; healing may restore original structures
but involves collagen deposition and scar
formation.
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50. Regeneration
• Regeneration refers to growth of cells and
tissues to replace lost structures, such as the
growth of an amputated limb in amphibians.
• Tissues with high proliferative capacity, such
as the hematopoietic system and the epithelia
of the skin and gastrointestinal tract, renew
themselves continuously and can regenerate
after injury, as long as the stem cells of these
tissues are not destroyed.
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51. Repair by scar formation
• Healing is usually a tissue response:
(1) to a wound (commonly in the
skin)
(2) to inflammatory processes in
internal organs, or
(3) to cell necrosis in organs
incapable of regeneration.
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52. TISSUE-PROLIFERATIVE ACTIVITY
• The tissues of the body are divided into three
groups on the basis of their proliferative activity.
• In continuously dividing tissues (also called labile
tissues) cells proliferate throughout life,
replacing those that are destroyed.
• These tissues include surface epithelia, such as
stratified squamous surfaces of the skin, oral
cavity, vagina, and cervix; the lining mucosa of
all the excretory ducts of the glands of the body
(e.g., salivary glands, pancreas…)
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53. TISSUE-PROLIFERATIVE ACTIVITY…
• Quiescent (or stable) tissues normally have a low
level of replication; however, cells from these
tissues can undergo rapid division in response to
stimuli and are thus capable of reconstituting the
tissue of origin.
• In this category are the parenchymal cells of liver,
kidneys, and pancreas; mesenchymal cells, such as
fibroblastsandsmoothmuscle; vascular endothelial
cells; and resting lymphocytes other leukocytes.
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54. TISSUE-PROLIFERATIVE ACTIVITY…
• Nondividing (permanent) tissues contain cells
that have left the cell cycle and cannot undergo
mitotic division in postnatal life.
• To this group belong neurons and skeletal and
cardiac muscle cells.
• If neurons in the central nervous system are
destroyed, the tissue is generally replaced by the
proliferation of the central nervous system
supportive elements, the glial cells.
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55. Proliferative Potential (to sum up)
• Labile cells - continuously dividing
– Epidermis, mucosal epithelium, GI tract
epithelium etc
• Stable cells - low level of replication
– Hepatocytes, renal tubular epithelium, pancreatic
acini
• Permanent cells - never divide
– Nerve cells, cardiac myocytes, skeletal mm.
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56. Repair by Healing, Scar Formation, and Fibrosis
• Regeneration involves the restitution of tissue components
identical to those removed or killed.
• By contrast, healing is a fibro-proliferative response that
"patches" rather than restores a tissue.
• It is a complex but orderly phenomenon involving a number
of processes:
•Induction of an inflammatory process in response to the
initial injury, with removal of damaged and dead tissue
•Proliferation and migration of parenchymal and
connective tissue cells
•Formation of new blood vessels (angiogenesis) and
granulation tissue
•Synthesis of ECM proteins and collagen deposition
•Tissue remodeling
•Wound contraction
•Acquisition of wound strength
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57. Repair by Healing, Scar Formation, and
Fibrosis cont…
• To all of these events occur in every repair reaction.
• The repair process is influenced by many factors,
including:
•The tissue environment and the extent of tissue
damage
•The intensity and duration of the stimulus
•Conditions that inhibit repair, such as the
presence of foreign bodies or inadequate blood
supply,
•Various diseases that inhibit repair (diabetes in
particular), and treatment with steroids
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58. Factors affecting Healing:
Systemic
• Nutrition
• Vitamin def.
• Age
• Immune status
• Other diseases
Local
• necrosis
• Infection
• apposition
• Blood supply
• Mobility
• Foreign body
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60. Cutaneous Wound Healing
• We discuss wound healing in the skin to illustrate
general principles of repair that apply to most
tissues.
• Although most skin lesions heal efficiently, the end
product may not be functionally perfect.
• Epidermal appendages do not regenerate, and
there remains a connective tissue scar in place of
the mechanically efficient meshwork of collagen in
the unwounded dermis.
• In very superficial wounds, the epithelium is
reconstituted and there may be little scar
formation.
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61. PHASES OF WOUND HEALING
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62. HEALING BY FIRST INTENTION (WOUNDS WITH OPPOSED EDGES)
• Skin wounds are classically described to heal
by primary or secondary intention.
• this distinction is based on the nature of the
wound rather than the healing process itself.
• The least complicated example of wound
repair is the healing of a clean, uninfected
surgical incision approximated by surgical
sutures.
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63. Pattern of wound healing cont…
• Such healing is referred to as primary union
or healing by first intention.
• The incision causes death of a limited
number of epithelial and connective tissue
cells as well as disruption of epithelial
basement membrane continuity.
•The narrow incisional space immediately fills
with clotted blood containing fibrin and blood
cells; dehydration of the surface clot forms the
well-known scab that covers the wound.
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64. Healing by
First Intention
Focal Disruption of
Basement Membrane and
loss of only a few epithelial
cells
e.g. Surgical Incision
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65. HEALING BY SECOND INTENTION (WOUNDS WITH SEPARATED EDGES)
• When there is more extensive loss of cells and
tissue, as in surface wounds that create large
defects, the reparative process is more
complicated.
• Regeneration of parenchymal cells cannot
completely restore the original architecture, and
hence abundant granulation tissue grows in from
the margin to complete the repair.
• This form of healing is referred to as secondary
union or healing by second intention.
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66. Secondary healing…
•Secondary healing differs from primary
healing in several respects:
•Inevitably, large tissue defects generate a
larger fibrin clot that fills the defect and
more necrotic debris and exudate that
must be removed.
• Consequently the inflammatory reaction
is more intense.
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67. Healing by
Second Intention
Larger injury, abscess,
infarction
Process is similar but
Results in much larger Scar
and then CONTRACTION
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68. Second intention…cont…
• Much larger amounts of granulation tissue are formed.
• Perhaps the feature that most clearly differentiates
primary from secondary healing is the phenomenon of
wound contraction, which occurs in large surface
wounds.
• The initial steps of wound contraction involve the
formation of a network of actin-containing fibroblasts at
the edge of the wound.
• Permanent wound contraction requires the action of
myofibroblasts—altered fibroblasts that have the
ultrastructural characteristics of smooth muscle cells.
• Contraction of these cells at the wound site decreases
the gap between the dermal edges of the wound.
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69. WOUND HEALING
• 1st INTENTION
• Edges lined up
• 2nd INTENTION
• Edges NOT lined up
• More granulation
• More epithelialization
• MORE FIBROSIS
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70. COMPLICATIONS IN CUTANEOUS WOUND
HEALING
• Complications in wound healing can arise from
abnormalities in any of the basic components of
the repair process.
• These aberrations can be grouped into three
general categories:
–(1) Deficient scar formation,
–(2) Excessive formation of the repair
components, and
– (3) Formation of contractures.
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71. Complication of wound cont..
•Inadequate formation of granulation tissue or
assembly of a scar can lead to two types of
complications:
1.wound dehiscence and
2. ulceration
•Dehiscence or rupture of a wound is most
common after abdominal surgery and is due to
increased abdominal pressure.
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72. Complication of wound cont..
•The accumulation of excessive amounts of
collagen may give rise to a raised scar known as a
hypertrophic scar;
•if the scar tissue grows beyond the boundaries of
the original wound and does not regress, it is
called a keloid.
• Keloid formation appears to be an individual
predisposition, and for unknown reasons this
aberration is somewhat more common in African-
Americans
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73. HYPERTROPHIC SCAR
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74. KELOID
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75. CONTRACTURES (CICATRISATION)
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76. BURN SCARS
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77. BONE FRACTURE HEALING
1. Hematoma formation
2. Inflammation
3. Soft callus
4. Hard callus
5. Remodeling
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78. FIBROSIS
• The mechanisms underlying the formation of
a cutaneous scar—cell proliferation, cell-cell
interactions, cell-matrix interactions, and ECM
deposition—are similar to those that occur in
the fibrosis associated with chronic
inflammatory diseases such as rheumatoid
arthritis, lung fibrosis, and hepatic cirrhosis.
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