Transcript CHRONIC INFLAMMATION

Cell Injury
 Cell injury occurs when a cell can no longer adapt to
stimuli.
 This can occur if the stimuli are too long in duration
or too severe in nature.
 Hypoxia,
microorganism infection, temperature
extremes, physical trauma, and radiation, cause cell
injury.
Cell Death
There are two main categories of cell death:
1-Necrotic cell death, characterized
by cell swelling and rupture of internal
organelles.
 Common causes of necrotic cell death
include prolonged hypoxia and infection .
2- Apoptosis, is not characterized by
swelling or inflammation, but rather the
dying cell shrinks on itself and then is
engulfed by neighboring cells.
 Viral infection of a cell will often turn on
apoptosis, ultimately leading to the death of
the virus and the host cell.
 Deficiencies
in apoptosis have been
implicated in the development of cancer .
Results of Cell Death
 Dead cells are removed from the area or
isolated from the rest of the tissue by
immune cells in the process of phagocytosis.
 If mitosis is possible and the area of necrosis
is not too large, new cells of the same type
fill in the empty space.
 Scar tissue will form in the vacated space if
cell division is impossible or if the area of
necrosis is extensive.
INFLAMMATION
 Definition: it is the vascular, lymphatic & cellular
reactions of the living tissue against an irritant by
which the defense mechanisms of the body can attack
the cause to prevent tissue damage.
 Aiming of localizing, destroying the irritant and
preparing for repair.
 Nomenclature :
appendicitis
suffix + itis e.g. tonsillitis –
Causes (the irritant):
 1-living
organisms e.g.
viruses,
bacteria,
fungi,
parasites.
 2-Physical agents e.g. radiation, trauma and burns.
 3-Chemical agents e.g. strong acids and alkalies.
 4-Injury by immunological mechanisms e.g.
hypersensitivity reaction.
 NB: it commonly results because of an immune
response to infectious micro-organisms.
Types of inflammation:
1- Acute
2- Chronic
ACUTE INFLAMMATION
 Definition: It is a type of inflammation caused by
mild or severe irritant.
 It is characterized by short duration and rapid tissue
response.
 “PROTECTIVE” RESPONSE
NON-specific
Mechanism of acute inflammation
 The manifestation of acute inflammation can be
divided into two categories:
 Vascular response.
 Cellular response.
 At the biochemical level, many of the responses that
occur during acute inflammation are associated with
the release of chemical mediators.
ACUTE INFLAMMATION
VASCULAR EVENTS
CELLULAR
EVENTS (PMN or
PolyMorphonuclear
Neutrophil,
Leukocyte?, “POLY”, Neutrophil,
Granulocyte,
Neutrophilic
Granulocyte
“MEDIATORS”
VASCULAR EVENTS
 a)Transient vasoconstriction: Due to direct action
of irritant.
 It lasts for few seconds
 It is a protective process
 b) Vasodilatation of arterioles, capillaries &
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venules
Causing redness and hotness due to increased blood
flow.
Caused by: a) Chemical mediators
b) Local axon reflex
Persists to the end of inflammation.
VASCULAR EVENTS
 Increase in capillary permeability, which cause fluid to
move into the tissues and cause swelling, pain, and
impaired function.
 The exudation or movement of the fluid out of the
capillaries and into the tissue spaces dilutes the offending
agent.
 As fluid moves out of the capillaries, stagnation of flow and
clotting of blood in the small capillaries occurs at the site
of injury.
 This
aids in localizing
microorganisms.
the
spread
of
infectious
LEAKAGE OF PROTEINACEOUS
EXUDATE, NOT
FLUID (
TRANSUDATE)
Cardinal signs of acute
inflammation:
Redness: Due to vasodilatation and increased blood Flow.
Hotness: Due to increased blood Flow.
Swelling: Due to fluid exudates
Pain: Due to stimulation of nerve endings by bradykinin
and PGE2 or its pressure by inflammatory oedema
Loss of function : Due to pain and tissue damage
Cellular response
 The cellular response of acute inflammation
is marked by movement of phagocytic white
blood cells (leukocytes) into the area of
injury.
 Two types of leukocytes participate in the
acute inflammatory response:
 The granulocyte (neutrophils, basophils &
esinophils) and
 Monocyte.
ACUTE
INFLAMMATION
Neutrophil
Polymorphonuclear
Leukocyte, PMN, PML
“Leukocyte”
Granulocyte, Neutrophilic
granulocyte
Neutrophils
 The neutrophil is the primary phagocyte that arrives
early at the site of inflammation.
 The
neutrophils cytoplasmic granules contain
enzymes and other antibacterial substances that are
used in destroying and degrading the engulfed
particles.
Esinophils
 These granulocytes increase in the blood during
allergic reactions and parasitic infections.
Basophils
 The granules of these granulocytes contain
histamine and other mediators of inflammation.
 The basophils are involved in producing the
symptoms associated with inflammation and
allergic reactions.
Monocytes
 These longer-lived phagocytes help to destroy the
causative agent, aid in the signaling process of specific
immunity, and serve to resolve the inflammatory
process.
 The monocytes, which migrate in increased numbers
into the tissues in response to inflammatory stimuli,
mature into macrophages.
Monocytes
 Within 24 hours, mononuclear cells arrive at the
inflammatory site, and by 48 hours, monocytes and
macrophages are the predominant cell types.
 The macrophages engulf larger and greater quantities of
foreign material than do the neutrophils.
 They also migrate to the local lymph nodes to prime
specific immunity.
 These leukocytes play an important role in chronic
inflammation, where they can surround and wall off
foreign material that cannot be digested.
B- Cellular response
 The sequence of events in the cellular
response to inflammation includes:
 1- Margination (Emigration).
 2-Pavementing.
 3- Migration
 4- Activation
 5- Chemotaxis.
 6- Phagocytosis.
 The
release of chemical mediators
(histamine, leukotrienes and kinins) and
cytokines affects the endothelial cells of the
capillaries and causes the leukocytes to
increase their expression of adhesion
molecules.
 As this occurs, the leukocytes slow their
migration and begin to marginate, or move
to and along the periphery of the blood
vessels.
B- Cellular exudates:
 i-
Margination
(emigration)
and
pavementation of leukocytes:
 In inflammation, due to slowing of the blood flow,
leucocytes leave the central zone to the peripheral
zone (margination), roll on endothelium, and
adhere to endothelium receptors (pavemetation).
 Several adhesion molecules on leucocytes and
endothelium serve for such steps e.g. selectin, Ig
superfamily and integrin.
 ii- Migration of leucocytes: leucocytes pass between
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endothelial cells by pseudopodia and traverse basement
membrane to extravasular connective tissue.
It is an active process, need energy and Ca++, helped by
chemotactic factors.
iii- Leucocytes activation: The net result of leucocytic
activation include:
-Secretion of cytokines and lysosomal enzymes
-Production of reactive oxygen species.
-Modulation of leucocytes adhesion molecules.
 N.B.

- PNLs. Escape early (6-24h),
-Monocytes escape late (1-2days) and become
phagoytic known as (marophages).

-Eosinophils increase in allergic inflammation
Mechanism of formation of
cellular exudate
CHEMOTAXIS
 Attraction of leucocytes towards the irritant by
chemotactic factors
leukotriens and IL8.
e.g:
bacterial
toxins,
C5a,
PHAGOCYTOSIS
 Definition: is the ingestion and destruction of foreign
body and bacteria by phagocytic cells.
 Engulfment by pseudopodia.
 Intracellular killing and degradation:
 Contact of the bacteria or antigen with the phagocyte
cell membrane is essential for trapping the agent and
triggering the final steps of phagocytosis.
Function : kill bacteria and help repair..
 Cytoplasmic extensions (pseudopods) surround and
enclose the particle in a membrane-bounded
phagocytic vesicle or phagosome.
 In the cell cytoplasm, the phagosome merges with a
lysosome containing antibacterial molecules and
enzymes that can digest the microbe.
Fate of acute inflammation:
 1-Resolution: When the cause of inflammation
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overcome by defensive mechanisms
2-Spread: a-local by breaking through fibrin barrier.
b-By natural passages e.g. ureters and
bronchi or serous membranes e.g. pleura and
peritoneum.
c- Lymphatic: Causing lymphangitis and
lymphadenitis.
d- Blood: Bacteremia, septicaemia or
pyaemia.
3-Chronicity: if the cause can not be completely
destroyed by the defensive mechanisms.
Types of acute inflammation
 I- Suppurative inflammation:
It in an acute
inflammation characterized by pus formation.
 A-localized suppurative inflammation
1-Abscess
A localized suppurative inflammation characterized by
formation of a cavity containing pus
2-Furuncle (boil)
Small abscess in relation to hair follicle or sebaceous
gland
3- Carbuncle
It is a localized suppurative inflammation characterized
by multiple communicating deep abscesses, open on the
surface by multiple sinuses.
CHRONIC INFLAMMATION
Definition:

 It is inflammation of prolonged duration (weeks or
months) in which active inflammation, tissue
destruction, and attempts of healing are proceeding
simultaneously.
Chronic inflammation occurs:
 1- After acute inflammation which fail to
cure.
 2- After repeated acute attacks.
 3- Or chronic from the start due to low
virulent organism (when it is caused by a
mild infection with a prolonged action such
as tuberculosis, rheumatoid arthritis,
atherosclerosis and chronic lung diseases).
 Characteristics
of chronic inflammation is an
infiltration by mononuclear cells (macrophages) and
lymphocytes.
 It also involves the proliferation of fibroblasts
instead of exudates.
 As a result, the risk of scarring and deformity usually is
considered greater than in acute inflammation.
CHRONIC INFLAMMATION
(MONOS)
MONOCYTE
LYMPHOCYTE
MACROPHAGE
HISTIOCYTE
Types of chronic inflammation:
 1-Specific: It is chronic inflammation caused by
specific organism which produces characteristic
histologic appearance. In many types of chronic
specific inflammation, the chronic inflammatory cells
may form tumour like mass called granuloma as in
TB and bilhariziasis.
 2-Non specific: It is chronic inflammation caused by
different types of organism which do not produce
characteristic histologic appearance.
GRANULOMATOUS INFLAMMATION
A granuloma is a focus of chronic specific
inflammation
consisting
of
a
microscopic
aggregation (1-2mm) of macrophages that are
transformed into epithelium-like cells (epitheloid
cells) surrounded by a collar of mononuclear
leukocytes, principally lymphocytes and occasionally
plasma cells.
 Offending agent could be mostly detected.
comparison between acute and
chronic inflammation
Acute inflammation
Sudden
Short
Present
-Onset
-Duration
-Vascular
phenomena
-Cardinal signs of
Present
inflammation
Acute type
-Toxemia
Mainly
-Cells
polymorphs.Histiocytes
appear later on.
-Blood vessels
Numerous,thin
walled,dilated and
congested.
Chronic inflammation
Gradual
Prolonged
Slight or absent
Slight or absent
Chronic type
Lymphocytes,plasma
cells,histiocytes ,giant
cells, fibroblast.
Less numerous,thick
walled and many show
 I-Changes in blood cells :
 A-WBC's:
 B- RBCs:
 2-Fever:
 3-loss of appetite
 4-Liver
 5-Hyperplasia
 6-Degenerative changes in parenhymatous
 7-Septicemia.
 8-Pyaemia.
GENERAL CHANGES (systemic
manifestations)OF ACUTE INFLAMMATION
 I-Changes in blood cells :
 A-WBC's: (normal leucocytic count: 5000-10000|mm3:
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*Leucocytosis: Increase number of WBC more than 10.000/mmm3.
IL-1 & tumor necrosing factor (TNF) released from macrophages,
stimulate bone marrow for proliferation of leucocytes and their release
to the circulation. e.g:
-Neutrophils increase in pyogenic or suppurative inflammation.
-Eosinphils increase in parasitic infection and allergic reactions.
-Lymphocytes increase in viral infection and chronic
inflammation.
-Monocytes increase in malaria.
*Leucopenia: Decrease number of leucocytes e.g. typhoid fever.
Effects of infection:
 1- Toxaemia
 2- Bacteraemia
 3- Pyaemia
 4- Septicemia.

 TOXEMIA presence in the blood of
bacterial toxins
 Bacteremia,
microorganisms
are
present in small numbers in the
bloodstream and do not multiply there
because they are rapidly removed by
the body's defense mechanisms.
 SEPTICEMIA denote a serious infection in which
large
numbers
of
microorganisms
have
overwhelmed the body's defense systems and are
actively multiplying in the bloodstream. Usually
associated with TOXEMIA and is manifested
clinically by high fever, chills, tachycardia, and
hypotension. Death may result.
 PYAEMIA is a serious condition with severe
toxemia.
 The organism escape into the blood stream in the
form of small aggregates-micro-emboli