INFLAMMATION

General Pathology

Session 2
 Learning objectives
At the end of this session, students should be able to:
• Define the term inflammation
• Explain cardinal signs of inflammation
• Explain types of inflammation
• Explain basic phenomena in acute and chronic
inflammation
• Explain the outcomes of inflammation
• Explain the mechanisms of tissue healing and repair
 Inflammation…

Inflammation.
• Is the complex host response to eliminate foreign invaders
(such as infectious pathogens) and damaged tissues. OR
• Inflammation is a protective response intended to eliminate
the initial cause of cell injury as well as the necrotic cells and
tissues resulting from the original insult.
Inflammation accomplishes its protective mission by
Diluting, Destroying, or Neutralizing harmful agents (e.g.,
microbes and toxins).
It then sets into motion the events that eventually heal and
repair the sites of injury
Although inflammation helps clear infections and other
noxious stimuli and initiates repair, the inflammatory reaction
and the subsequent repair process can cause considerable harm.
 Cardinal signs of inflammation.
These are external manifestations of
inflammation which results from the vascular
changes and cell recruitment.
The cardinal signs are:
• Heat (calor),
• Redness (rubor),
• Swelling (tumor).
• Pain (dolor) and
• Loss of function (functio laesa),
 Types of inflammation.
There are two types of inflammation:
• Acute inflammation
• Chronic inflammation
Acute inflammation- Is a rapid response to injury or
microbes and other foreign substances that is designed to
deliver leukocytes and plasma proteins to sites of injury. OR
- Is a body response which is rapid in onset and of short
duration, lasting from a few minutes to as long as a few
days, and is characterized by fluid and plasma protein
exudation and a predominantly neutrophils leukocyte
accumulation.
 Continue…..
• Chronic inflammation is inflammation of
prolonged duration (weeks to months to years)
in which active inflammation, tissue injury, and
healing proceed simultaneously.
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).
 Basic phenomena in acute and chronic
inflammation
• Transudate is the fluid, mainly blood plasma with little
proteins that moves from capillaries into the tissues during
early phase of inflammation and various non-inflammatory
conditions.
• Exudates is the fluid, reach in proteins and even cells, that
moves from the capillaries into the tissues during
inflammation.
• Effusion is the fluid, relatively poor in proteins, found in
serous cavities due to serous inflammation.
 Continue……
The 5 steps of the inflammatory response are:
• Recognition of the injurious agent
• Recruitment of leukocytes
• Removal of the agent
• Regulation (control) of the response
• Resolution (repair)
 Causes of acute inflammatory reactions
• Infections. (bacterial, viral, fungal, parasitic) are among the most common
and medically important causes of inflammation.
• Trauma. (blunt and penetrating)
• Physical and chemical agents. (thermal injury, e.g burns or frostbite;
irradiation; some environmental chemicals) injure host cells and elicit
inflammatory reactions.
• Tissue necrosis. (from any cause), including ischemia (as in a myocardial
infarct) and physical and chemical injury.
• Foreign bodies. (splinters, dirt, sutures)
• Immune reactions. (also called hypersensitivity reactions) against
environmental substances or against self tissues. Since these stimuli can t
be eliminated and tend toe persist, and areimportant causes of morbidity
and mortality. "Immune-mediated inflammatory disease" is sometimes
used to refer to this group of disorders.
 Sequence of Events in Acute Inflammation
• The vascular changes:
-Increased blood flow secondary to arteriolar and capillary bed dilation (erythema
and warmth).
-Increased vascular permeability, either through widened inter-endothelial cell
junctions of the venules or by direct endothelial cell injury, results in an exudate of
protein-rich extravascular fluid (tissue edema).
• Cellular changes:
-The leukocytes, (initially predominantly neutrophils), adhere to the endothelium
via adhesion molecules, then leave the microvasculature and migrate to the site of
injury under the influence of chemotactic agents.
-Phagocytosis, killing, and degradation of the offending agent follow. Genetic or
acquired defects in leukocyte functions give rise to recurrent infections.
 The outcome of acute inflammation may be;
• Removal of the exudate with restoration of normal tissue architecture (resolution);
• Transition to chronic inflammation; or
• Extensive destruction of the tissue resulting in scarring.
 Causes of chronic inflammation.
• Persistent infections.
Microbes that are difficult to eradicate [ mycobacteria, Treponema
pallidum (causative organism of syphilis), and certain viruses and fungi,]
• Immune-mediated inflammatory diseases. (hypersensitivity diseases).
Diseases that are caused by excessive and inappropriate activation of the
immune system are increasingly they include to autoimmune diseases
(rheumatoid arthritis) and allergic diseases, such as bronchial asthma
• Prolonged exposure to potentially toxic agents. Examples include
non-degradable exogenous materials (e.g inhaled particulate silica,
which can induce a chronic inflammatory response in the lungs
(silicosis), and
• Endogenous agents. Such as chronically elevated plasma lipid
components, which may contribute to atherosclerosis
 Events in chronic inflammation
• Infiltration with mononuclear cells (including
macrophages, lymphocytes, and plasma cells)
• Tissue destruction (largely induced by the
products of the inflammatory cells)
• Repair [involving new vessel proliferation
(angiogenesis)] and
• Fibrosis.
 Chronic Inflammatory Cells:
• Macrophages
Macrophages, the dominant cells of chronic inflammation, are tissue cells
derived from circulating blood monocytes after their emigration from the
bloodstream. Macrophages are normally diffusely scattered in most
connective tissues, and are also found in organs such as the liver (where they
are called Kupffer cells), spleen and lymph nodes (called sinus histiocytes),
central nervous system (microglial cells), and lungs (alveolar macrophages).
• Lymphocytes.
Lymphocytes are mobilized to the setting of any specific immune stimulus
(i.e., infections) as well as non-immune-mediated inflammation (e.g., due to
infarction or tissue trauma).
Both T and B lymphocytes migrate into inflammatory sites using some of the
same adhesion molecule pairs and chemokines that recruit other leukocytes.
 Continue…….
• Plasma cells
Plasma cells develop from activated B lymphocytes and produce antibodies
directed either against persistent antigens in the inflammatory site or against
altered tissue components.  
• Eosinophils.
Eosinophils are characteristically found in inflammatory sites around parasitic
infections or as part of immune reactions mediated by IgE, typically associated
with allergies.
Eosinophil granules contain major basic protein, a highly charged cationic protein
that is toxic to parasites but also causes epithelial cell necrosis.
• Mast cells
Mast cells are found distributed in connective tissues throughout the body, and
they can participate in both acute and chronic inflammatory responses. In
individuals prone to allergic reactions, IgE-armed mast cells are central players in
allergic reactions, including anaphylactic shock
HEALING AND REPAIR
 OBJECTIVES
– Define healing, regeneration and fibrosis
– Describe the cell cycle and the role of growth
factors in healing
– To describe factors influencing wound
healing
– To describe the complications of wound
healing
 HEALING:
Definition:- is the body response to injury in an
attempt to restore normal structure and function.
The process of healing involves 2 distinct processes:

1. REGENERATION
2. REPAIR

Usually the two processes are both involved in the

restoration of tissue.
 HEALING:CONT--
1. REGENERATION: when healing takes place by
proliferation of parenchymal cells (specialized tissue) and
usually results in complete restoration of original tissue.

2. REPAIR: when healing takes place by proliferation of

connective tissue elements resulting in fibrosis and
scarring.
 1. REGENERATION:
• In order to maintain proper structure of tissues,
parenchymal cells are under constant regulatory
control of their cell cycle.

• Growth factors play a major role in the regulation of

the cell cycle. These include:
– epidermal growth factor
– fibroblast growth factor
– platelet growth factor
– endothelial growth factor
– transforming growth factor β
THE CELL CYCLE
 THE CELL CYCLE
 Is defined as the period between two successive cell
divisions,consists of equal phases.
 M phase: Mitosis/ division
 G1 phase (gap1) : after mitosis
 S phase (Synthesis) : synthesis of nuclear DNA
 G2 phase (gap2) : after completion of nuclear DNA
duplication.
 G0 phase (gap0) : this is the quiescent or resting
phase of the cell cycle after M phase.
 THE CELL CYCLE
– Not all cells of the body divide at the same
pace.
– Some mature cells do not divide at all, while
others complete the cycle every 16-24 hours.
 Capacity to divide of cells:
 Depending upon their capacity to divide, the cells of
the body can be divided into 3 groups:-
– Labile cells
– Stable cells
– Permanent cells
 Labile cells:
– These cells continue to multiply throughout life
under normal physiologic conditions.
– These cells include:
• Surface epithelial cells of epidermis
• Alimentary tract
• Respiratory tract
• Urinary tract
• Vagina, Cervix, endometrium
• Haematopoietic cells of bone marrow and
• Cells of lymphnodes and spleen
 Stable cells:
The cells decrease their ability to proliferate after
adolescence but retain the capacity to multiply in
response to stimuli throughout adult life.
 Stable cells include:
Parenchymatous cell;
Liver
Pancrease
Kidneys
Adrenals
Thyroid …

 Mesenchymal cells;
 Smooth muscle cells
 Fibroblasts
 Vascular endothelium
 Bone and cartilage cells …
 Permanent cells:
 These cells lose their ability to proliferate
around the time of birth.
– These cells include:
• Neurons of CNS
• Skeletal muscle cells
• Cardiac muscle cells
 RELATIONSHIP OF PARENCHYMAL CELLS
WITH CELL CYCLE.
 If the 3 types of parenchymal cells described
above are correlated with the phase of cell
cycle, the following inferences can be
derived:-
• Labile cells which are continuously dividing
cells which remain in the cell cycle from one
mitosis to the next
• Stable cells are in the resting phase (G0) but
can be stimulated to enter the cycle
• Permanent cells are non-dividing cells which
have left the cycle and die after injury.
 Parenchymal cells cont--
Regeneration of any type of parenchymal
cells involves the following 2 processes:
• Proliferation of original cells from the
margins of injury with migration so as
to cover the gap.
• Proliferation of migrated cells with
subsequent differentiation and
maturation so as to reconstitute the
original tissue.
 II: REPAIR:
Definition:- repair is the replacement of
injured tissue by fibrous tissue.
 Two processes are involved in repair:-
• GRANULATION TISSUE
FORMATION;
• CONTRACTION OF WOUNDS
 Repair response takes place by
participation of;
 Participation of cells in repair
• Mesenchymal cells
– Connective tissue stem cells
– Fibrocytes
– Histiocytes
• Endothelial cells
• Macrophages
• Plateletes
• Parenchymal cells of the injured organ
 GRANULATION TISSUE

 The following 3 phases are observed in

the formation of granulation tissue.

 Phase of inflammation:-
• Following trauma, blood clots at the site
of injury.
• There is acute inflammatory response
with exudation of plasma, neutrophils
and some monocytes within 24 hours.
 GRANULATION TISSUE
 Phase of clearance:-
There is a combination of;
 Proteolytic enzymes liberated by
neutrophils,
 Autolytic enzymes from dead tissue
cells and
 Phagocytic activity of macrophages
clear off the necrotic tissue, debris and
red blood cells.
 GRANULATION TISSUE
 Phase of ingrowth of granulation
tissue:-
This phase consists of 2 main processes.
 Angiogenesis or Neovascularisation
 Formation of fibrous tissue
Angiogenesis (Neovascularisation):
• Formation of new blood vessels at the site
of injury takes place by proliferation
arterioles, thin-walled venules and
capillaries. proliferation of endothelial cells
from margins of blood vessels
• The newly formed blood vessels are more
leaky, accounting for the oedematous
appearance of new granulation tissue Soon,
these blood vessels differentiate into
muscular
 Angiogenesis (Neovascularisation):
• The process of angiogenesis takes place
under the influence of the following:-

 Endothelial cell growth factors which

act as positive stimuli and appear in
granulation tissue
 Type IV collagen which acts as negative
stimuli and appear late in the
granulation tissue formation
 Fibrous tissue formation:

• The new fibroblasts originate from

fibrocytes as well as by mitotic division of
fibroblasts.
• Some of the fibroblasts have morphologic
and functional characteristic of smooth
muscle cells (Myofibroblasts)
 Fibrous tissue formation:
cont--
• Collagen fibril begin to appear by about
6th day.
• As maturation proceeds, more and more
of collagen is formed while the active
fibroblasts and new blood vessels
decreases.
• This results in the formation of inactive
looking scar known as Cicatrisation.
CONTRACTION OF WOUNDS:
• The wounds starts to contracting after 2-3
days and the process is completed by the
14th day.
• During this period, the wound is reduced
by approximately 80% of its original size
• Contracted wounds results in rapid
healing since lesser surface area of the
injured tissue has be replaced.
CONTRACTION OF WOUNDS:
• The mechanism of wound contraction is
thought to operate through the
myofibroblasts which appear in active
granulation tissue
These cells have features intermediate
between those of fibroblasts and smooth
muscle cells.
Their migration into the wound area and their
act of contraction decreases the size of the
defect.
 Skin WOUND HEALING:

• Healing of skin wounds provides a classical

example of combination of regeneration and
repair described above.
• This can be accomplished in one of the
following two ways:-
 Healing by first intention (primary union; and
 Healing by second intention (secondary
union).
 I. Healing by first intention (primary
union):
• This is defined as healing of a wound
which has the following characteristics:
clean and uninfected
Surgically incised
Without much loss of cells and tissue and
Edges of wound are approximated by
surgical sutures
 The sequence of events in primary union

• The sequence of events in primary union

are as follows:-
 Initial haemorrhage.
 immediate after injury, the space
between the approximated surfaces of
incised wound is filled with blood which
clots and seals the wound against
dehydration and infection
 Acute inflammatory response

 This occurs within 24 hours with appearance

of polymorphs from the margins of incision
 By the 3rd day, polymorphs are replaced by
macrophages

 Epithelial changes.
 The basal cells of the epidermis from both the
cut margins start proliferating and migrating
towards incisional space in the form of
epithelial spurs
 Epithelial changes.cont-

 A well approximated wound is covered by a

layer of epithelium in 48 hours.
 By 5th day, a multilayered new epithelium
is formed.
 Organization.
 By 3rd day, fibroblasts also invade the
wound area.
 By 5th day, new collagen fibril start
forming which dominate till healing is
complete
 In 4 weeks the scar tissue with scanty
cellular and vascular elements, a few
inflammatory cells and epithelialised
surface is formed.
 II. Healing by second intention:
 This is defined as healing of wound having the
following characteristics:-
– open with large tissue defect, at times
infected
– having extensive loss of cells and tissues and
– the wound is not approximated by surgical
sutures but left open.
 II: Healing by second intention:cont--

 The basic events in secondary union are similar

to primary union but differ in having larger
tissue defect which has to be bridged
 Healing takes place from the base upwards as
well as from the margins inwards.
 The healing by second intention is slow and
results in a large and at times ugly scar as
compared to rapid healing and neat scar of
primary union.
 II: Healing by second intention:
 The sequence of events in secondary union is
as follows:-
 Initial haemorrhage:
 as a result of injury, the wound space is filled
with blood and fibrin clot which dries
 Inflammatory phase:
 There is initial acute inflammatory response
followed by appearance of macrophages
which clear the debris as in primary union.
 Healing by second intention:
 Epithelial changes:
 The epidermal cells from both margins of
wounds proliferate and migrate into wound in
the form of epithelial spurs till they meet in
the middle and reepithelialise the gap
completely
 However, the proliferating epithelial cells do
not cover the surface fully.
 Healing by second intention:

 Granulation tissue:
 The main bulk of secondary healing is by granulations.
 Granulation tissue is formed by proliferation of fibroblasts
and neovascularisation from adjoining viable elements.
 Wound contraction:
 contraction of wound is an important feature of secondary
healing, not seen in primary healing.
 Due to action of myofibroblasts the wound contracts to one-
third or to one-fourth of its original size.
 Healing by second intention:

 Presence of infection:
 Bacterial contamination of an open wound
delays the process of healing due to release of
bacterial toxins.
• FACTORS INFLUENCING WOUND
HEALING:
 LOCAL FACTORS:
• Infections: - delay the process of healing
• Poor blood supply:- slows healing
• Foreign bodies:- interfere with healing
and cause intense inflammatory reaction
and infection.
• Exposure to ionizing radiation:- delays
granulation tissue
 Cont..
• Exposure to ultraviolet light:- facilitates
healing
• Types, size and location of injury:- determines
whether healing takes place by resolution or
organization
 FACTORS INFLUENCING WOUND
HEALING:
 SYSTEMIC FACTORS:
• Age:- wound healing is rapid in the young and
some what slow in aged and debilitated people
due to poor blood supply to the injured area in
the latter.
• Nutrition:- deficiency of constituents like
protein, vitamin C (Scurvy) and Zinc delays
wound healing.
 FACTORS INFLUENCING WOUND
HEALING:
 SYSTEMIC FACTORS: cont—
 Systemic infection:- delays wound healing
 Administration of glucocorticoids (drugs):-
has an anti-inflammatory effect.
 Uncontrolled diabetics:- because are more
prone to develop infections and hence delay
wound healing.
 Haematologic abnormalities like:- defects in
neutrophil function (chemotaxis and
phagocytosis), Neutropenia, and Bleeding
disorders – slow the process of wound
healing.
COMPLICATIONS OF WOUND
HEALING
 Implantation (epidermal) cyst formation due to
persistence of epithelial cells in the wound after
healing
 Deficient scar formation: - this may occur due
to inadequate formation of granulation tissue
 Incisional hernia: - a weak scar may be the site
of bursting open of a wound (wound
dehiscence) or incisional hernia.
 Cont..

 Hypertrophic scar and Keloid

formation:- excessive formation of
collagen in healing result in keloid
 Excessive contraction:- may result in
formation of contractures or
cicatrisation
 Neoplasm:- rarely scar may be the site
of development of carcinoma eg.
Squamous cell carcinoma
Hypertrophic scar
Keloid
Keloid scar
Thanks