9. 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
10. Haemodynamic changes Transient vasoconstriction Persistant
progressive vasodilatation Slowing or stasis of blood Margination
Pavementing Emigration
11. 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
12. 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
13. 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
14. Slowing or stasis of blood Slowing or stasis of
microcirculation follows which causes increased concentration of
red cells and thus increased viscocity
15. 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
16. 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
17. 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.
18. 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
19. OSMOTIC PRESSURE OF INTERSTITIAL FLUID TISSUE HYDROSTATIC
PRESSURE INTRAVASCULAR HYROSTATIC PRESSUE OSMOTIC PRESSURE OF
PLASMA PROTEINS OUTWARD MOVEMENT OF FLUID INWARD MOVEMENT OF FLUID
STARLINGS HYPOTHESIS
20. 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
21. 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 Rivaltas 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
23. 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
24. 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)
25. 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(TNF). The onset of
response takes 4-6 hours after injury and lasts for 2-4 hrs or
more
26. 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
27. 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
28. 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
29. Cellular events Exudation of leucocytes Phagocytosis
30. EXUDATION OF LEUCOCYTES Changes in the formed elements of
blood Rolling and adhesion Emigration Chemotaxis
31. 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
32. PHAGOCYTOSIS RECOGNITION & ATTACHMENT KILLING OR
DEGRADATION ENGULFMENT The process of engulfment of solid
particulate material by the cell. 2 types: a) Microphages b)
macrophages
34. 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
37. Polymorphonuclear Leukocytes Along with basophils and
eosiniphils these are known as granulocytes- due to presence of
granules in cytoplasm. DIAMETER: 10-15 m, 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.
38. 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
39. 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
40. 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
41. 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.
42. 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.
45. 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)
46. 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.
47. 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.
48. 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)
49. OXYGEN DERIVES METABOLITES: released from activated
neutrophils and monocytes include O2, 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
50. 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
51. 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
52. FATE OF ACUTE INFLAMMATION
53. 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.
57. 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 (Hashimotos disease), auto-immune
atrophic gastritis, adrenal atrophy, etc. Reactions to altered
self-antigens, e.g. contact dermatitis to rubber, nickel, etc
58. 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
59. 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 Crohns disease
are also associated with granulomas
60. ? 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.
61. 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
62. 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)
63. NSAIDs: Drug Effects Analgesic (mild to moderate) Anti-gout
Anti-inflammatory Antipyretic Relief of vascular headaches Platelet
inhibition (ASA)
64. Role in inflammation
65. 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 bodys glucocorticoid
activity and the bodys ability to produce this substance
naturally
68. 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
