inflammation; acute and chronic

2. objectives
 Overview
 Historical aspect
 classification
 Acute inflammation
 Mediators of inflammation
 MorphologicPatterns of Inflammation
 Outcomes of AcuteInflammation
 Systemic effects on inflammation

3. INFLAMMATI
ON
Protective
Mechanism
Tissue damage
Necrotic
tissue
Foreign
Invader
Plasma
protein
leukocyte phagocytes
Types
Acute
chronic
B
U
T
adly
ncontrolled
riggered
Inflammatory Response
TISSUE
INJURY

7. Classification of inflammation
 1- According to principle
constituent of exudates:-
SEROUS
FIBRINOUS
HAEMORRAGIC
PURULENT
ACUTE
INFLAMMATION

8. II-According to duration
 Per-acute inflammation
 Acute inflammation
 Sub-acute inflammation
 Chronic inflammation

9. III-According to fate of
inflammation:-
 Hyperplastic inflammation
 Hypertrophic inflammation
 Atrophic inflammation
 Fibrous inflammation
 Adhessive inflammation:

10. IV- According to the cause:
 Mechanical inflammation
 Physical inflammation
 Chemical Inflammation
 Biological inflammation

11. Agents causing inflammation
Infective
agents
Immunologi
cal agents
Physical
agents
Chemical
agents
Inert
materials
Bacteria
Viruses and
their toxins,
fungi,
parasites
Cell mediated
Antigen
antibody
reactions
Heat
Cold
Radiation
Mechanical
trauma
Organic
Inorganic
poisons
Foreign bodies

13. characteristic
 RapidHostResponse
 Alterationsinvascularcalibre
 Increasebloodflow
 Structuralchangesinmicrovasculature
 Plasmaprotein&Leukocyteleave
circulation
 Emigration
 Leukocyte
 Toaccumulateininjuriousfoci
normal
inflamed

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

16. Haemodynamic changes
 Transient vasoconstriction
 Persistant progressive vasodilatation
 Slowing or stasis of blood
 Margination
 Pavementing
 Emigration

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

25. OSMOTIC
PRESSURE OF
INTERSTITIAL
FLUID
TISSUE
HYDROSTATIC
PRESSURE
INTRAVASCULAR
HYROSTATIC
PRESSUE
OSMOTIC
PRESSURE OF
PLASMA
PROTEINS
OUTWARD
MOVEMENT OF
FLUID
INWARD
MOVEMENT OF
FLUID
STARLING’S
HYPOTHESIS

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

29. • Hallmark of acute inflammation
• 3 types:
• Immediate transient response:
• Immediate sustained response:
• Delayed prolonged leakage:

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

40. Cellular events
 Exudation of leucocytes
 Phagocytosis

41. EXUDATION OF LEUCOCYTES
 Changes in the formed elements of blood
 Rolling and adhesion
 Emigration
 Chemotaxis

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

44. PHAGOCYTOSIS
RECOGNITION &
ATTACHMENT
KILLING OR
DEGRADATION
ENGULFMENT
The process of engulfment of solid particulate material
by the cell.
2 types:
a) Microphages
b) macrophages

45. PHAGOCYTO
SIS
RECOGNITION AND ATTACHMENT
Opsonins - C3b, IgG, lectins
ENGULFMENT STAGE
Cytoskeletal mechanisms
Degranulation
KILLING / DEGRADATION
O2-Dependent - H2O2 HOCl
O2-Independent - lysozyme, cationic proteins,
defensins, lactoferrin
NO -Dependent

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

48. Release of soluble mediators
Vasodilation
Increased blood flow
Extravasation of fluid (permeability)
Cellular influx (chemotaxis)
Elevated cellular metabolism
Heat (calor)
Redness (rubor)
Swelling (tumor)
Pain (dolor)
Physiological Symptoms
Responses

49. INFLAMMATORY CELLS

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.

57. Chemical mediators

58. Mediators of inflammation
Mediators Principal sources Actions
CELL DERIVED
Histamine Mast cell, basophil,
platelet
Vasodilation , increased vascular
permeability, pain, endothelial
activation
Serotonin Chromaffin cells of
GIT, spleen & platelet
Vasodilation , increased
permeability
Prostaglandin Mast cell, leukocyte Vasodilation, pain, fever
Leukotrienes Mast cell, leukocyte Increase permeability, Chemotaxis,
leukocyte adhesion & activation
Platelet- activating factor Leukocyte, mast cell Increase permeability,
bronchoconstriction, chemotaxis
Reactive Oxygen Species Leukocyte Microbicidal, Tissue damage
Nitric Oxide Endothelium,
Macrophages
Vascular smooth muscle relaxation
Cytokine ( TNF, IL-1)
Chemokines
Macrophage, mast cell
leukocyte
Local endothelial activation
Chemotaxis, leukocyte activation

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)

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)

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

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

79. FATE OF ACUTE INFLAMMATION

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.

82. DIFFUSE
SUPPURATIVE
GRANULOMATOUS
FIBRINOID
CHRONIC
INFLAMMATION

83.  Is the persistence of inflammation with attempts
of repair resulting from persistence of the
injurious agent.

84.  Persisting infection or prolonged exposure to irritants
(intracellular surviving of agents -TB)
 Repeated acute inflammations (otitis, rhinitis)
 Primary chronic inflammation -low virulence, sterile
inflammations (silicosis)
 Autoimmune reactions (rheumatoid arthritis,
glomerulonephritis, multiple sclerosis)

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

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.

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

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)

101. NSAIDs: Drug Effects
 Analgesic (mild to moderate)
 Anti-gout
 Anti-inflammatory
 Antipyretic
 Relief of vascular headaches
 Platelet inhibition (ASA)

102. Role in inflammation

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

105. How it Works

106. Adverse effect of corticosteroids
 Receive long-term, high-dose steroid
 Hypertension, heart failure
 Osteoporosis, DM, impaired wound healing, metal depression
and psychosis
 Peptic ulcer, Cataract, glaucoma, growth suppression,
hypocalcemia, PTH increased
 Cushing syndrome
 Secondary adrenal insufficiency

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