14. Acute inflammation
VASCULAR EVENTS CELLULAR EVENTS
HAEMODYNAMIC CHANGES
Transient vasoconstriction
Persistent progressive vasodilatation
Local hydrostatic pressure
Slowing or stasis of blood
ALTERED VASCULAR PERMEABILITY
Contraction of endothelial cells
Retraction of endothelial cells
Direct injury to endothelial cells
Endothelial injury mediated by
leucocytes
Neovascularisation
EXUDATION OF LEUCOCYTES
Changes in formed elements of
blood
Rolling and Adhesion
Emigration
Chemotaxis
PHAGOCYTOSIS
Recognition and attachment
Engulfment
Killing and degradation
17. TRANSIENT VASONSTRICTION
Irrespective of the type of
injury , immediate vascular
response is of transient
vasoconstriction of arterioles.
With mild form of injury, the
blood flow may be
reestablished in 3-5 seconds
while with more severe injury
the vasoconstriction may last
for about 5 minutes
18. Persistant progressive vasodilatation
Involves mainly the arterioles
but to lesser extent other
components of the
microcirculation like venules and
capillaries
This change is obvious within
half an hour of injury
Vasodilatation results in
increased blood volume in
microvascular bed of the
area,which is responsible for
redness and warmth at the site of
acute inflammation
19. Local hydrostatic pressure
Progressive vasodilatation may elevate local hydrostatic
pressure resulting in the transudation of fluid into the
extracellular space
This is responsible for swelling at the local site of acute
inflammation
20. Slowing or stasis of blood
Slowing or stasis of microcirculation follows which
causes increased concentration of red cells and thus
increased viscocity
21. margination
Stasis or slowing is followed by leucocyte margination
Peripheral orientation of leucocytes along the vascular
endothelium
Leucocytes rolls over the surface of endothelial cells and
is called pavementing
22. emigration
The leucocytes stick to the vascular endothelium briefly
and then move and migrate through the gaps between the
endothelial cells into the extravascular space. This process
is called emigration
23. SIR THOMAS LEWIS : established the concept
that chemical substances, locally induced by
injury, mediate the vascular changes of
inflammation.(1924)
The reaction so elicited is known as TRIPLE
RESPONSE or REDLINE RESPONSE consisting
of following:
Redline: appears within a few seconds following
stroking & results from local vasodilation of
capillaries & venules.
Flare: is the bright reddish appearance or flush
surrounding the redline & results from
vasodilation of adjacent arterioles.
Wheal: is the swelling or edema of the
surrounding skin occurring due to transudation of
fluid into the extravascular spaces.
24. Alteredvascular permeability
The appearance of inflammatory oedema due to
increased vascular permeability of microvascular bed is
explained on the basis of starlings hypothesis
In normal circumstances the fluid balance is maintained
by two opposing sets of forces
26. Forces that cause outward movement of fluid from
microvasculation are intravascular hydrostatic pressure
and colloid osmotic pressure of interstitial fluid
Forces that cause inward movement of interstitial fluid
into circulation are intravascular colloid osmotic pressure
and hydrostatic pressure of interstitial fluid
27. Transudate Exudate
Filtrate of blood plasma without
changes in endothelial
permeability
Non inflammatory edema
Ph more than 7.3
Few cells ,mainly mesothelial
and cellular debris
Oedema of inflamed tissue
associated with increased
vascular permeability
Inflammatory edema
Ph less than 7.3
Many cells, inflammatory as
well as parenchymal
Rivalta’s test:: is a very simple, inexpensive method that does not require special
laboratory equipment and can be easily performed in private practice. This test was
originally developed by the Italian researcher Rivalta around 1900 and was used to
differentiate transudates and exudates in human patients.
A test tube is filled with distilled water and acetic acid is added. To this mixture one drop
of the effusion to be tested is added. If the drop dissipates, the test is negative, indicating
a transudate. If the drop precipitates, the test is positive, indicating an exudate
30. Mechanisms of increased vascular
permeability
Contraction of endothelial cells
Retraction of endothelial cells
Direct injury to endothelial cells
Endothelial injury mediated by leucocytes
Leakiness in neovascularisation
31. Contraction of endothelial cells
This is the most common mechanism of increased
leakiness that affects venules exclusively while capillaries
and arterioles remains unaffected
The endothelial cells develop temporary gaps between
them due to their contraction resulting in vascular
leakiness
It is mediated by the release of histamine, bradykinin and
other chemical mediators
The response begins immediately after injury, is usually
reversible and is for short duration(15-30 minutes)
32. Retraction of endothelial cells
In this mechanism, there is structural re-organisation of the
cytoskeleton of endothelial cells that causes reversible
retraction at the intercellular juctions
This change too affects venules and is mediated by cytokines
such as interleukin 1 and tumor necrosis factor(TNFα).
The onset of response takes 4-6 hours after injury and lasts for
2-4 hrs or more
33. Direct injury to endothelial cells
Direct injury to the endothelium causes cell necrosis and
appearance of physical gaps at the sites of detached endothelial
cells
Process of thrombosis is initiated at the site of damaged
endothelial cells
The increased permeability may either appear immediately
after injury and last for several hours or days ,or may occur
after a delay of 2-12 hours and lasts for hours or days
34. Endothelial injury mediated by
leucocytes
Adherence of leucocytes to the endothelium at the site of
inflammation may result in activation of leucocytes
The activated leucocytes release release proteolytic
enzymes and toxic oxygen species which may cause
endothelial injury and increased vascular leakiness
This form of increased vascular leakiness affects mostly
venules and is a late response
35. Leakiness in neovascularisation
The newly formed capillaries under the influence of
vasculr endothelial growth factor(VEGF) during the
process of repair and in tumours are excessively in leaky
41. EXUDATION OF LEUCOCYTES
Changes in the formed elements of blood
Rolling and adhesion
Emigration
Chemotaxis
42.
43. CHEMOTAXIS
After exiting the circulation leukocyte emigrate in
tissues towards the site of injury by a process called
chemotaxis.
Exogenous and endogenous substance can act as
chemoattractants.
Exogenous – bacterial products.
Endogenous- 1) cytokines- IL-8
2) Leukotriene- B4
3) components of complement system.
4) soluble bacterial products
47. Lymph flow is increased
Drains edema fluid that accumulate at
extra vascular space
Lymph channels proliferate to control
the edema
Painfull enlargement of draining lymph
node – LYMPHADENITIS
Secondarily infected lymphatics –
LYMPHANGITIS
TELLTALE sign
red streak near wound
indicative of infection
involvement of lymphatics
50. Polymorphonuclear
Leukocytes
Along with basophils and
eosiniphils these are known as
granulocytes- due to presence of
granules in cytoplasm.
DIAMETER: 10-15 μm, active motile
40-75% of circulating leukocytes
Arise in the bone marrow from
stem cell.
No. increased in blood and tissues
in acute inflammation.
Function: initial phagocytosis,
engulfment, harmful effects.
51. Eosinophils
1-6%of WBCs
Similarities like PMNs-
Production in bone marrow,
locomotion, phagocytosis, lobuled
nuclues, granules in cytoplasm
containing variety of enzymes.
Granules richer in
myeloperoxidase
prominent in allergic reactions,
parasitic infections, skin disease,
malignant lymphomas.
live longer than PMNs, are present
in chronic inflammation
52. Basophils
1% of WBCs
Contain coarse basophilic
granules in the cytoplasm &
polymorphonuclear nucleus.
Granules laden with heparin
& histamine.
most prominent in allergic
reactions regulated by
immunoglobulin E
rich in vasoactive substances
histamine
precursors of mast cells
53. Macrophages
Blood monocytes 4-8% of
wbc.
appear 3-4 days after infection
or tissue destruction
long life span, present in
chronic inflammation
capable of phagocytosis
rich in lytic enzymes
secrete cytokines locally and
systemically
recruit lymphocytes to site of
inflammation
54. Lymphocytes
main means of providing the
body with immunity
20-45% of the WBCs
Present in blood, spleen,
thymus, lymphnode, MALT.
Scanty cytoplasm & consists
almost entirely of nucleus.
In tissues: dominant cells in
chronic inflammation & in late
stage of acute inflammation.
In blood: no. increased in
lymphocytosis.
55. Plasma cells
Eccentric nucleus, abundant
cytoplasm
Nucleus has cart-wheel pattern
of chromatin
Develop from B-lymphocytes, &
rich in RNA.
MOST ACTIVE IN ANTIBODY
SYNTHESIS.
Increased in prolonged infection
with immunological response-
syphilis, rheumatoid arthritis,
hypersensitivity states, Multiple
myeloma.
59. Mediator Principal source Functions
PLASMA PROTEIN
DERIVED
Complement Products
(C5a, C3a, C4a)
Plasma (produced in liver)
Leukocyte chemotaxis and
activation, vasodialation
Increased permeability,
smooth muscle contraction
Vasodilation, pain.
Endothelial activation,
leukocyte recruitment
Kinins Plasma (produced in liver)
Protease activated during
coagulation
Plasma (produced in liver)
60.
61.
62.
63. Lysosomal components
Inflammatory cells- neutrophils and monocytes, contain
lysosomal granules which on release elaborate a variety of
mediators of inflammation.
1) granules of neutrophils-
a) primary or azurophilic- myeloperoxidase, acid hydrolase,
acid phosphatase.
b)secondary or specific- lectoferrin, gelatinase, collagenase
c)tertiary granules- gelatinase, acid hydrolase.
2) granules of monocytes and tissue macrophages-
plasminogen activator, protease, elastase.
64. Platelet Activating Factor
Released from IgE- sensitised basophils and mast cells,
other leucocytes, endothelium and platelets.
ACTIONS:
1) Increased vascular permeability
2) bronchoconstriction
3) adhesion of leukocytes to endothelium
4) chemotaxis
5) vasodilation- in low conc.
65. CYTOKINES
Cytokines are polypeptide substances produced by
activated lymphocytes and activated monocytes.
Major cytokines are: IL-1, TNF- alpha and beta, IFN-
gamma, chemokines (IL-8 , PF-4)
66.
67. OXYGEN DERIVES METABOLITES: released from
activated neutrophils and monocytes include O’2,
H2O2, OH’ and toxic NO products.
Actions: 1) endothelial cell damage 2) activation of
protease 3)damage to other cells.
NITRIC OXIDE: vascular relaxation factor produced by
endothelial cells.
Action: 1)vasodilation, 2)anti-platelet activating
agent, 3)possibly microbicidal action
68.
69.
70.
71. THE COMPLEMENT SYSTEM
The activation of this complement system can occur either:
1) By classic pathway through antigen- antibody complex or,
2) by alternate pathway via non-immunologic agents such as
bacterial toxins, cobra venoms and IgA.
ACTIONS:
1) C3a, C5a, C4a activate mast cells and basophils to release of
histamine, cause increased vascular permeability causing
oedema in tissues
2) C3b is an opsonin
3) C5a is chemotactic for leukocytes
4) C5b-C9 are lipid dissolving agent
72. Systemic effects of acute inflammation
Fever
Leucocytosis (15-20,000)
Bacterial infection- Neutrophilia
Viral infection -Lymphocytosis
Parasitic infection- Eosinophilia
Hypotension
Increased ESR and C-reactive protein
80. refferences
Basics of Pathology, Robins & Cotrans
Essential pathology for dental students, 4th edition,
Harsh Mohan.
Inflammation- a review of the process, 5th edition.
Henry o. trowbridge.
85. Mechanism......
Defective acute inflammatory response
Poor blood supply
Poor general nutrition
Abnormal neutrophil function
Anti-inflammatory drugs, especially corticosteroids
Agent is resistant to phagocytosis and/or intracellular destruction
Intracellular infectious agents, e.g. tuberculosis, salmonellosis, brucellosis, viral
infections
Foreign-body reactions
The provoking agent is a body constituent as in:
Auto-immune diseases, e.g. diffuse lymphocytic thyroiditis (Hashimoto’s
disease), auto-immune atrophic gastritis, adrenal atrophy, etc.
Reactions to altered self-antigens, e.g. contact dermatitis to rubber, nickel, etc
86. Continuing some features of acute inflammation
Polymorph infiltration
Fibrinous exudation
Increased vascularity
Features of healing-repair and/or regeneration
Infiltration by chronic inflammatory cells
Lymphocytes
Plasma cells
Macrophages
Eosinophils
87.
88. Granulomatous inflammation
A distinct pattern of chronic inflammation
characterized by formation of granulation tissue.
It is a protective response to chronic infection or
foreign material, preventing dissemination and
restricting inflammation.
Some autoimmune diseases such as rheumatoid
arthritis and Crohn’s disease are also associated
with granulomas
89. ? Granuloma.......
A granuloma is a localized mass of granulation tissue with aggregations
of chronic inflammatory cells
The granuloma consists of a kernel of infected macrophages
surrounded by foamy macrophages and a ring of lymphocytes and a
fibrous cuff.
90.
91. Causes of granuloma......
Bacteria:
Tuberculosis, Leprosy, Syphilis, Actinomycosis
Parasites:
Schistosomiasis
Fungi:
Histoplasmosis, Blastomycosis
Foreign bodyGranulomas
Endogenous
keratin, necrotic bone or adipose tissue uric acid crystals
Exogenous
wood, silica, asbestos, silicone
Unknown cause such as sarcoidosis
92.
93.
94.
95. Inflammatory reaction is greater in diabetic status
Conversely local inflammation causes intensification of
diabetes
According to Russel in 1966
Cellular dehydration
Loss of alkali reserve
Vessels lumen get obliterated
Thickening of capillaries - Role in inflammation acts as a barrier to
leukocytic emigration into site (Brayton et al 1970)
96.
97.
98.
99.
100.
101. NSAIDs: Drug Effects
Analgesic (mild to moderate)
Anti-gout
Anti-inflammatory
Antipyretic
Relief of vascular headaches
Platelet inhibition (ASA)
104. Chemical Make-Up
Hydrocortisone or cortisol is the primary agent
Glucocorticoid, which is naturally secreted by body is
derivative
Currently, many AI steroids are available more powerful than
cortisol, but have the same chemical structure as glucocorticoid
Long term use will inhibit body’s glucocorticoid activity and
the body’s ability to produce this substance naturally
110. conclusion
Humans owe to inflammation & repair their ability to
contain injuries & heal defects. Without
inflammation, infections would go unnoticed, would
never heal, & injured organs might remain permanent
festering sores. However inflammation & repair may be
potentially harmful