Post on 15-Dec-2014
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INTRODUCTION TO INFLAMMATION
CONCEPTION Inflammation is a complex reaction to injurious agents
that consists of vascular response, cellular reaction, and systemic reactions.
a defensive response fundamentally
be divided into acute inflammation and chronic inflammation
Inflammation is a protective response
.
Purpose of inflammation:
1.To dilute, localize and destroy the injurious agent2.To limit tissue injury3.To restore the tissue towards normality
•Sometimes however inflammation may be harmful e.g. inflammation due to hypersensitivity reaction
•Inflammations are mostly indicated by suffix “itis” e.g. appendicitis
Type of inflammation:
1.Acute inflammation2.Chronic inflammation
Acute inflammation: It is an immediate response to an injurious agent and last for minutes, hours or a few days Histologically, it is associated with
a.Exudation of fluid, plasma proteinb.Migration of leukocytes predominantly neutrophil
Chronic inflammation: It persists for week or monthsHistologically, it is associated with
a.Proliferation of blood vessels and connective tissueb.Accumulation of lymphocytes and macrophage
Cause of inflammation:
1.Infectious agent: Bacteria, virus, fungi, and protozoa
2.Immunologic agent: Hypersensitivity reaction e.g. allergy rheumatoid arthritis
3.Physical agent: Mechanical injury like cut, cold, heat, radiation
4.Chemical agent: Strong acid, alkali, and phenol
INTRODUCTION TO INFLAMMATION
CARDINAL CLINICAL SIGNS acute inflammation has 5 cardinal signs:acute inflammation has 5 cardinal signs:
Rubor- RednessRubor- Redness
Calor- HeatCalor- Heat
Tumor- SwellingTumor- Swelling
Dolor- PainDolor- Pain
Loss of functionLoss of function
increased blood flowto the inflamed area
accumulation of fluid
release of chemicals that stimulate nerve endings
a combination of factors
Time course
Acute inflammation: Less than 48 hours
Chronic inflammation: Greater than 48 hours (weeks, months,
years)
Cell type
Acute inflammation: Neutrophils
Chronic inflammation: Mononuclear cells (Macrophages,
Lymphocytes, Plasma cells).
MEDIATORS OF ACUTE INFLAMMATION
A variety of endogenous chemical mediators play some important roles in the modulation of inflammatory response.
Originated from cells or plasma:
Cell-derived mediators:
sequestered in intracellular granules and synthesized in response to a stimulus
Plasma-derived mediators:
present in precursor form and activated by proteolytic cleavage
SUMMARY OF INFLAMMATORY MEDIATORS
Function Major mediators
Vasodilation 5-HT,histamine, bradykinin ,PGE2
Permeability 5-HT,histamine, C3a, C5a, PAF
Chemotaxis C5a, LTB4, cytokins
Fever Cytokines( IL-1, 6, TNF), PG
Pain PGE2 , bradykinin
Tissue damage Lysosomal enzymes , NO
Pathogenesis:
Three main processes occur at the site of inflammation, due
to the release of chemical mediators :
Increased blood flow (redness and warmth).
Increased vascular permeability (swelling, pain & loss of
function).
Leukocytic Infiltration.
Mechanism of Inflammation
1. Vaso dilatation
2. Exudation -
Edema
3. Emigration of
cells
4. Chemotaxis
The major local manifestations of acute inflammation, compared to normal.
(1) Vascular dilation and increased blood flow (causing erythema and warmth).
(2) Extravasation and deposition of plasma fluid and proteins (edema).
(3) leukocyte emigration and accumulation in the site of injury.
Changes in vascular flow (hemodynamic changes)
Slowing of the circulation
outpouring of albumin rich fluid into the extravascular
tissues results in the concentration of RBCs in small
vessels and increased viscosity of blood.
Leukocyte margination
Neutrophil become oriented at the periphery of vessels
and start to stick.
Changes that occurs in the site of inflammation: (in summary)
1.Release of various chemical substances like histamine, Bradykinin, serotonin, prostaglandin, several reaction products of compliment system, reaction products of blood-clotting system and multiple hormonal substance called lymphokines which cause overall process of inflammation
2.Vasodilation of local blood vessels, so increase in local blood flow to inflamed area (erythremia)
3.Increase permeability of capillaries with leakage of large quantities of fluid and plasma protein like fibrinogen into interstitial space (swelling)
4.Migration of large number of granulocytes and monocytes in tissue
5.Finally healing by growth of fibrous tissue
Lymphatics in inflammation:
Lymphatics are responsible for draining edema.
Edema: An excess of fluid in the interstitial tissue
or serous cavities; either a transudate or an
exudate
Transudate: An ultrafiltrate of blood plasma
permeability of endothelium is usually
normal.
low protein content ( mostly albumin)
Exudate:
A filtrate of blood plasma mixed with inflammatory cells and
cellular debris.
permeability of endothelium is usually altered
high protein content.
MORPHOLOGIC AND FUNCTIONAL CHANGES
The two main components of the acute inflammatory:
The microcirculatory response
The cellular response
THE MICROCIRCULATORY RESPONSE
vasodilation and stasis
increased permeability
exudation of fluid
THE MICROCIRCULATORY RESPONSE
A. vasodilation and stasis
in the microcirculation a transient vasoconstriction (induced by action of mediators)
dilation of arterioles, capillaries, and venules (hyperemia)
stasis
THE MICROCIRCULATORY RESPONSE
B. increased permeability
in venules and capillaries
active contraction of actin filaments in endothelial cells
direct damage to endothelial cells
leukocyte-mediated endothelial injury
transcytosis increased
permeability increase
(reversible)
THE MICROCIRCULATORY RESPONSEB. increased permeability in venules and capillaries
Three phases of increased permeability in acute inflammation:
(1) an immediate phase
(2) a delayed response
(3) a prolonged response
These permeability changes are effected by various chemical mediators
THE MICROCIRCULATORY RESPONSE
C. exudation of fluid
exudation: increased passage of fluid out of the microcirculation because of increased vascular permeability
the composition of an exudate approaches that of plasma, but rich in proteins
fibrinogen is converted to fibrin rapidly exudation should be distinguished from transudation
Grossly, fibrin is seen on an acute inflamed serosal surface that changes to a rough, yellowish bread andbutter-like surface, covered by fibrin and coagulatedproteins.
THE MICROCIRCULATORY RESPONSE
C. exudation of fluid
The functions of exudation:
(1) dilute the offending agent
(2) cause increased lymphatic flow, conveying noxious agents to the draining lymph nodes to facilitating a protective immune response
(3) flood the area with plasma, which contain numerous defensive proteins
THE CELLULAR RESPONSE
leukocyte infiltration plays an important role
in limiting the spread of injury
in defending the host tissue
Acute inflammation is characterized by the active
emigration of inflammatory cells from the blood into the
area of injury.
THE CELLULAR RESPONSE
Extravasation: the process of the leukocytes from the vessel lumen to the interstitial tissue.
3 steps of extravasation :
(1) margination, rolling and adhesion to
endothelium in the lumen
(2) transmigration across the endothelium
(3) migration toward the site of injury
THE CELLULAR RESPONSE
A. types of cells involved neutrophils
(polymorphonuclear leukocytes)
phagocytic cell of the macrophage system
lymphocytes and plasma cells
THE CELLULAR RESPONSE
B. margination, adhesion and transmigration of neutrophils
THE CELLULAR RESPONSE
C. emigration of neutrophils
take 2-10minutes
intercellular junctions
basement membrane
THE CELLULAR RESPONSE
D. chemotactic factors
chemotaxis: In the interstitial tissue, neutrophils move toward the site of injury, oriented along a chemical gradient.
chemotactic factors: Govern the active emigration of neutrophils and the direction in which they move.
THE CELLULAR RESPONSEE. Phagocytosis
Recognition
opsonization: the agent has been coated with immunoglobulin or complement factor 3b (opsonins).
Engulfment
the agent + opsonins phagosome
Microbial killing phagosome fuses with lysosomes, therefore the enzymes can
access to the engulfed microorganism and kill them
engulfment
PROCESS OF PHAGOCYTOSIS
THE CELLULAR RESPONSE
F. Erythrocyte
The orderly flow of blood is disturbed in the dilated vessels
Erythrocyte form heavy aggregates and sludging
Erythrocyte enter an inflamed area passively
Diapedesis
Hemorrhagic inflammation
Walling-off effect of inflammation:
One of the first results of inflammation is to “wall off” the area of injury from the remaining tissue. The tissue space and the lymphatics in the inflamed area are blocked by fibrinogen clots, so that fluid barely flow through the space. This walling-off process delays the spread of bacteria to toxic products
Different line of defense process of inflammation:
A.First-line defense:
Tissue macrophage is the first line of defense.
Within minutes after inflammation begins, the macrophage already present in tissue like histiocytes, alveolar macrophage, being their phagocytic action Mechanism:
Product of inflammation
Activates tissue macrophage
Rapid enlargement of these cells
These macrophages break loose from their attachments and become mobile
Serves are first line of defense during the first hour or so
B.Second-line defense:
Neutrophilic invasion of inflamed area is a second line of defense
•Within the first hour or so after inflammation begins, large number of neutrophils begin to invade the inflamed area from the blood. This invasion is due to products from inflamed tissue.
•Thus within several hours after tissue damage begins, the area becomes well supplied with neutrophils, because the blood neutrophils are already mature cells, they are ready to begin immediately their scavenger functions for killing bacteria and removing foreign matter.
C.Third-line defense:
A second macrophage invasion of the inflamed tissue is a third line of defense •Along with invasion of neutrophil, monocyte from blood enter the inflamed tissue and after hours enlarge to form macrophage
• Monocytes in blood are few in number also storage pool of monocytes in bone marrow is less• In addition to that monocytes require few hours to acquire full phagocytic capacity.
Therefore, the buildup of macrophages in inflamed tissue and to become dominant phagocytic cell of inflamed tissue is much slower than that of neutrophils requiring several days to several weeks .
D.Fourth-line defense
Increased production of granulocytes and monocytes by the bone marrow is a fourth line of defense.
Increased production is due to stimulation of granulocytic and monocytic progenitor cell of bone marrow
It takes 3-4 days before newly form granulocyte and monocyte reach the stage of leaving the bone marrow
If the stimulus from inflamed tissue continues, the bone marrow can continue to produce these cells in tremendous quantities for months and even years, sometimes at rates of production 20 to 50 times normal.
ACUTE INFLAMMATION HAS ONE OF FOUR OUTCOMES:
Abscess formation
Progression to chronic inflammation
Resolution--tissue goes back to normal
Repair--healing by scarring or fibrosis
Inflammation Outcome
Acute Inflammati
on
Resolution
Chronic Inflammati
onAbsce
ss
Sinus
Fistula
Fibrosis/Scar
Ulcer
Injury
FungusVirus
CancersT.B. etc.
Feedback control of macrophage and neutrophil response:
There are five major important factors that play dominant role in the control of macrophage-neutrophil response of inflammation.
They are:
1.Tumor necrosis factor (TNF)
2.Interleukin-1 (IL-1)
3.Granulocyte-monocyte colony stimulating factor (GM-CSF)
4.Granulocyte colony stimulating factor (G-CSF)
5.Monocyte colony stimulating factor (M-CSF)
These factors increase production of granulocyte and monocyte by bone marrow
These factors are formed by:
1.Activated macrophage
2.T-cell in the inflamed tissue
3.Other inflamed tissue cell
Pus:
When neutrophil and macrophage engulf large number of bacteria and necrotic tissues, all neutrophil and many, if not most of macrophage die, so after several days, a cavity is formed in inflamed tissue
This cavity contains varying portion of necrotic (dead) tissue, dead neutrophils, dead macrophage, and tissue fluid. Such a mixture is called pus and cavity, which contain pus, is called abscess.
After the infection has been suppressed, dead cells and necrotic tissue in pus gradually autolyze over a period of days and the end products are usually absorbed into surrounding tissues until most of evidence of tissue damage is gone.
Leucopoiesis: Process of production of WBC under normal physiological condition
Granulopoiesis: The process of production of granulocytes under normal physiological condition.
Leukocytosis: Increased number of WBC above its upper normal limit Is increase in total white cell count above 11,000/mm3 in peripheral blood in adult
The particular white cell series affected varies with underlying cause
Neutrophilia:
1.Infection: e.g. abscess, acute appendicitis, tonsillitis, bacterial pneumonia 2.Non-infectious inflammatory disorder like rheumatic fever3.Tissue injury due to infarction: Myocardial infarction, burn, surgery4.Hemorrhage5.Stress: Childbirth, severe pain
Eosinophilia:
1.Helminthic infection: Hookworm, roundworm, tapeworm, filariasis2.Allergic reaction: Asthma, hay fever, urticaria3.Familial eosinophilia4.Tropical eosinophilia5.Loeffler’s syndrome
Lymphocytosis:
1.Bacterial disease: Whooping cough, tuberculosis2.Viral disease: Viral hepatitis, chicken pox, mumps, infectious mononucleosis3.Protozoal disease: Chronic malaria, kalazar
Leukopenia: Means reduction in total white cell count below 4000/mm3
Causes:1.Bacterial infection: Typhoid and paratyphoid fever2.Viral infection: Influenza, measles3.Aplastic anemia4.Megaloblastic anemia5.Hyperspleenism6.X-ray irradiation7.Cytotoxic drug
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