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3. 7. CHEMICAL MEDIATORS
8. MORPHOLOGICAL PATTERNS OF
ACUTE INFLAMMATION
9. CHRONIC INFLAMMATION
10. SYSTEMIC EFFECTS OF
INFLAMMATION
11.REGULATORS OF INFLAMMATION
12. FACTORS DETERMINIG VARIATIONS
IN RESPONSE
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4. Introduction
Defined as
“Local response of living tissues to injury due
to any agent”
Fundamentally protective response
Ultimate goal is to get rid of intial cause cell
injury(microbes, toxins)
Consequence of such injury(necrosis, tissues)
without inflammation wounds go unchecked, never
heal
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5. HISTORICAL HIGHLIGHTS
3000B.C Egyptians first described
1st century Celsus described cardinal signs
1793 John hunter inflammation not
disease, non specific response
that has salutary effect on host
1839 Conheihm used microscope to
observe changes in vessels
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6. 1880 Metchinkoff discovered phagocytosis
Paul ehrlich proposed humoral theory
of immunity
1908 Both got nobel prize
1924 Lewis explained role of chemical
mediators in inflammation
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8. EVOLUTION OF INFLAMMATION
Sponges , coelenterates body cavity is filled
with coelum, cells are called coelomocytes
Mollusca , urochordates body cavity is filled
With hemocele, cells are hemocytes
Amebocytes are seen in urochordates
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9. Invertebrates respond to local injury by
Phagocytosis
Encapsulation(similar to granuloma formation)
Neutralization of noxious stimuli by hypertrophy of
cells
Chemical mediators are also seen in some
invertebrates
A F Rowley The evolution of inflammation ; journal of
inflammation vol-5 1996
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11. Non living
Trauma - osteomyelitis Heat – burns
Ionizing radiation Uv light, infared
Chemicals , acids, alkalies Foreign body
Idiopathic
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12. GENETIC VARIATIONS
Variations in inherited genes can place them
at risk/ predispose them to inflammatory Disease.
These usually don’t cause disease by themselves
Unless they are challenged by particular trigger
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14. FUNCTIO LAESA – loss of function (later added
by galen and virchow in 3rd century)
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15. Rubor
Redness is due to
VASODILATION (DUE TO RELEASE OF MEDIATORS)
INCREASED BLOOD SUPPLY
TRIPLE RESPONSE OF LEWIS(1924)
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16. RED LINE APPEARS IN A
FEW SECONDS
DUE TO VASODILATION OF
CAPILLARIE AND VENULE
FLARE
FLUSH AROUND
RED LINE
APPEARS SLOWLY DUE TO AXON REFLEX
CAUSING DILATION OF
ADJACENT ARTERIOLES
WHEAL
SWELLING
OEDEMA
APPEARS IN MINUTES DUE TO TRANSUDATION OF
FLUID INTO EXTRA VASCULAR
SPACE
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17. CALOR
Due to increase in blood supply
Due to increase in metabolic activity in that area
Appreciation of heat is possible in superficial areas
with heat receptors… e.g : skin subcutaneous tissues
In deeper organs although associated with heat
in the area , it is not associated with perception of
increased heat
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18. Due to release of mediators which stimulate nerve
endings
Occurs only when appropriate sensory N. endings
exists in inflamed area
Type of pain depends on extent of stimulus rather
than type of causative agent
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19. REFERRED PAIN:
Due to spread of pain stimuli along the
nerves to relevant spinal segment and relay of
pain sensation to other areas served by same
segmental distribution
E.g Pain of myocardial ischemia referred to
left shoulder
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20. PAIN CAUSED BY
INFLAMMATION OF
CHARACTER
SKIN BURNING , ITCHING
DENSE TISSUES LIKE PERITONIUM
BONE , ENCAPSULATED ORGANS DULL , BORING , ACHING
PROGRESSED TO SUPPURATION THROBBING
PUS REACHES TO SURFACE SHARP , DARTING ,LANCINATING
NERVE TRUNK BORING , TINGLING
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21. TUMOR/SWELLING
Due to increased vascularity
Accumulation of fluid and cells in damaged part
EDEMA- Excess fluid in interstitial / serous cavities
it may be exudate / transudate in nature
PUS: Purulent exudate rich in leukocytes(mostly
neutrophils), debris of dead cells and in many cases
microbes
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22. EXUDATE TRANSUDATE
Edema of inflammed tissues
due to alteration in normal permeability
of small bvs
Ultrafiltrate of blood plasma that results from
osmotic/hydrostatic imbalance across the
vessel wall
Inflammatory edema Non inflammatory edema
High protein(2.5-3.5g/dl) readily coagulates
due to high fibrinogen
Low protein (>1g/dl)mainly albumin
low fibrinogen, no tendency to coagulate
Specific gravity >1.018
ph <7.3
Specific gravity low<1.015
ph>7.3
Glucose is low(<60mg/dl) same as plasma
LDH is high LDH is low
Many cells, inflammatory , parenchymal cells Few cells mainly mesothelial cells and cellular
debris
e.g: purulent exudate such as pus Edema in congestive cardiac failurewww.indiandentalacademy.com
23. TYPES OF INFLAMMATION
Acute inflammation
Rapid response to an injurious agent that serves to
deliver mediators of host defense , leukocytes and
plasma proteins to the site of injury
Chronic inflammation
Inflammation of prolonged duration in which active
inflammation, tissue destruction, and attempts at
repair are proceeding simultaneously
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27. Five mechanisms of increased vascular
permeability
Venules,vasoactiv
mediators
Imm transient
Venules
IL-1, TNF
DELAYED
Persists till
intercellular
junction
forms
Toxins
Chemicals
Imm,
sustained
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28. 1.Mediators bind to endothelium
Activates intracellular signaling pathways
Lead to phosphorylation of contractile proteins like
myosin
Imm…….15 to 30 minutes……..so transient
2.Cytokines cause structural reorganisation of
cytoskeleton causing retraction
3. Direct injury……….sustained…….till vessel wall
repaired
4. Neutrophils while migrating secrete proteases, ros
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29. In places like bbb tight junctions exisist
between endothelial cells
Cell cytoplasm communicates with exterior
through a process called transcytosis
Vesicles are formed from cytoplasm
Called vesiculovacular organelle
In infl……inc VDGF..............inc in no these
channels…..leadin to inc vas.perm
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31. CELLULAR EVENTS
EXUDATION
The escape of fluid, protein, and blood cells from
vascular system into interstitial tissue/body cavities
Changes leading to migration are
Changes in formed elements of blood
Rolling and Adhesion ,Emigration
Chemotaxis
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32. NORMAL
AXIAL FLOW
• RBC , WBC in the centre
• Peripheral zone of plasma
INFLAMMATION
• Leakage of plasma-narrowing of peripheral zone
• Redistribution of leukocytes to periphery-
MARGINATION
EMIGRATION
• Endothelium is virtually lined by leukocytes –pavementing
• Tumble slowly , adhere transiently –ROLLING ADHESION
• After firm adhesion leukocytes insert pseudopods into
intercellular junctions and escape into extra vascular space
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34. ADHESION MOLECULES INVOLVED IN INFLAMMATION
SELECTINS
3 closely related proteins( P, E , L) function in adhesion
They differ in their cellular distribution
L-SELECTIN/CD62L
Expressed in lymphocytes/other leukocytes
Founds on tips of microvillus projection of leukocytes
Facilitating it interaction with ligands on endothelium
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35. E-SELECTIN
Previously know as endothelial leukocyte
adhesion molecule
Expressed on cytokine activated endothelial cells
P-SELECTIN
Present on secretory granules of platelets
also found in granules of endothelial cells
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36. INTEGRINS
30 structurally homologus proteins
promote cell-cell/cell-matrix interactions
IMMUNOGLOBULIN SUPER FAMILY ADHESION
MOLECULES
ICAM VCAM
Leukocytes express CHOligands for selectins, integrins
These are low affinity reactions
Fast off rate…easily disrupt by flowing blood
As a result bound WBC detach and bind again
roll along endothelial surface
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37. ENDOTHELIAL
MOLECULE
LEUKOCYTE RECEPTOR ROLE
P-SELECTIN SIALYL-LEWIS X ROLLING
E-SELECTIN SIALYL –LEWIS X ROLLING ,ADHESION
ICAM-1 CD 11/CD18 INTEGRINS ADHESION,
TRANSMIGRATION
VCAM-1 ALPHA 4, BETA 1 ADHESION
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39. CHEMOTAXIS
Locomotion oriented along a chemical gradient
Chemokines acts chemoattractants for specific leukocytes
C-X-C Chemokine / alpha chemokine NEUTROPHILS
C-C Chemokine/beta chemokine
Acts On Eosinophils, Basophils, Monocytes, Lymphocytes
e.g: MCP, EOTAXIN
C-Chemokine/gamma LYMPHOCYTES
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40. Chemokines mediate their activities by binding to
seven transmembrane coupled receptor
Receptors are CXCR, CCR, CR
(CXCR-4, CCR-5 act as co receptor for viral envelope
glycoprotein of HIV and thus are involved in entry
and binding of virus)
chemokines stimulate leukocyte recruitment
and control normal migration of cells through various
tissues
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41. Leukocyte activation
Once recruited to site of injury, they must be activated
Stimuli are
Microbes, Necrotic cells
Ag-Ab complex
cytokines
Leukocytes express a number of receptors
on their surface
Toll like receptors – recognize LPS
Cytokine receptor
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43. PHAGOCYTOSIS
DEFINED AS
Process of engulfment of solid
particulate material by cells
Steps involved are
Recognition and attachment stage
Engulfment stage
Digestion/degradation stage
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44. RECOGNITION AND ATTACHMENT
The process of coating a particle , such as
microbe to target it for phagocytosis is called
OPSONISATION
substances are called opsonins
Main opsonin present in serum are
IGg opsonin(Fc) PMN possess receptor
C3b opsonin
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45. • Tuftsin is a phagocyte enhancing material in serum
• Acts directly on cell to stimulate phagocytosis
• 2 types of disorders
1. congenital an abnormal peptide competitively inhibit
2.deficiency seen in splenectomy
• Due to lack of tuftesin releasing enzyme from spleen.
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46. Engulfment
This is accomplished by formation of pseudopod
around particle due to actin filament beneath cellwall
Eventually complete closure of particle with in a
phagosome created by plasma membrane
Limiting membrane of phagocytic vacuole fuses with
Lysosome - phagolysosome
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50. Oxygen dependent
By production of reactive oxygen metabolites
HOCl , HOI , HOBR , HYDROGEN PEROXIDE, HYDROXYL
NADPH OXIDASE present in cell membrane of
phagosome reduces it to superoxide anion
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51. MPO dependent killing
MPO acts on hydrogen peroxide in presence of
halides to form hypohalous acid
This is more potent antibacterial agent
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52. MPO independent killing
Mature macrophages lack MPO
They carry out bactericidal actions by
forming hydroxyl ions
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53. Oxygen independent
Agents released from phagocytic cells
donot require oxygen
These include
Lysosomal hydrolases
Permeability increasing factors
Defensins
Cationic proteins
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55. Chemical Mediator Of Inflammation
• Also called permeability factors
• Induce their action by binding to specific
receptors on target cells
• Stimulate target cell to release secondary
effector molecules
Two types:
1. Cell derived
2. Plasma derived
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57. Histamine
First autacoid to be discovered
Formed from histidine by decarboxylation
Synthesized in all tissues
More in skin , lungs , GIT
Stored in high concentration in mast cells and
basophils
Involved in inflammation and anaphylactic reactions
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61. HISTAMINE ANTAGONISTS/ ANTI HISTAMINES
Bovet got nobel prize in 1944
Inhibit action of histamine by blocking receptor
Inhibit enzyme histidine decarboxylase
(atypical antihistamines)
H1 ANTAGONISTS: USED TO TREAT ALLERGY
First generation second generation
Chlorpheneramine Fexofenadine
Diphenhydramine Loratidine
Promethazine, hydroxyzine Levo Cetrizine
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62. serotonin
Also called 5-hydroxytryptamine(5HT)
Formed from L-Tryptophan
Present in platelets and enterochromaffin cells
Actions are similar to histamine
Vaso constrictor
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63. ARACHIDONIC ACID METABOLITES
20 CARBON PUFA
Derived from dietary source
Conversion of linoleic acid
Does not occur freely in cell but esterified
in membrane phospholipids
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68. Neutral proteases are capable of degrading
various extracellular component
Collagen, Basement membrane,
Fibrin, Elastin, Cartilage
Also cleave C3 and C5 directly releasing
anaphylotoxins
This results in tissue destruction
Because of its destructive effects ,if initial
leukocyte infiltration if left unchecked results in
tissue damage
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72. NITRIC OXIDE METABOLITES
Factor released from ENDOTHELIAL CELLS
Also called ENDOTHELIAL DERIVED RELAXING
FACTOR
Also from MACROPHAGES and NEURONS in brain
Synthesized from L-ARGININE by enzyme
nitric oxide synthetase(NOS)
3 types
eNOS endothelial produced at low levels
nNOS neuronal calcium influx cause rapid production
iNOS inducible (cytokines)
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73. ROLE IN INFLAMMATION
Potent vasodilator
Reduces platelet aggregation
Reduce leukocyte adhesion
Inhibit several features of mast cell
induced inflammation
Endogenous regulator for leukocyte recruitment
No and its derivatives are microbicidal
NO is an endogenous compensatory mechanism
that reduces inflammatory response
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76. COMPLEMENT SYSTEM
Consists of 20 component proteins and
their cleavage products
Found in plasma
Function in both innate and adaptive immunity
In process of complement activation a number
of components are elaborated that cause
- Increased vascular permeability
- Chemotaxis
- Opsonisation
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79. C3a and C5a
Stimulate histamine release
Anaphylotoxins
They have effects similar to mast cell mediators
C5a
Activates LOX pathway
Powerful chemotactic agent
Role in leukocyte adhesion
C3b
Acts as opsonin
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80. REGULATION OF COMPLEMENT ACTIVATION
The activation of complement is controlled by
cell associated and circulatory regulatory proteins
Regulation of C3 and C5convertase
Regulators function by enhancing dissociation
of convertase complex
E.g: decay accelerating factor
Proteolytic cleaving of C3b
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81. Binding of active complement components by
specific proteins in plasma
C1 binding to immune complex is blocked by
C1 INHIBITOR(C1INH)
Deficiency of C1INH is associated with
HERIDITARY ANGIONEUROTIC EDEMA
Episodic edema in skin, extremities, laryngeal
and intestinal mucosa provoked by stress/trauma
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82. KININ SYSTEM
Hageman factor [XII]
Activated Hageman Factor [XIIa]
prekallikrein activator (fragment of XIIa)
Plasmakallikrein Kallikrein
HMW Kininogen Bradykinin
Contact with
-ve charged
Collagen,Basement
membrane
cofactor for
Activation of
XII
chemotaxis
C5 to C5a
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83. BRADYKININ
Potent vasodilator
Increases vascular permeability( lower BP)
Causes constriction of smooth muscles
Pain
But the actions are short lived
As it is quickly inactivated by kininase
Any remaining kinin is inactivated by passage of
plasma through lung (degraded by ACE)
SO ACE INHIBITORS PREVENTS
DEGRADATION THERE BY FURTHER LOWERING BP
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87. Morphological patterns of acute inflammation
Serous inflammation
Marked by outpouring of thin fluid
Derived either from plasma
Or secretions of mesothelial cells
lining peritoneal, pleural, pericardial cavities
E.g: skin blister resulting from burn
viral infection causing fluid accumulation
either within or immediately beneath epidermis
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88. Fibrinous inflammation
Due increased permeability, severe injury large
molecules such as fibrinogen pass vascular barrier
Fibrin is formed and deposited in extracellular space
Fibrinous exudates are removed by fibrinolysis,
clearing of debris by macrophages
If it is not removed it may stimulate ingrowth of
fibroblasts, blood vessels leading to scarring
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89. Suppurative/purulent inflammation
Characterised by formation of pus
An accumulation of pus in enclosed
tissue spaces - ABSCESS
Certain bacteria like staphylococci
produce this localised suppuration
E.G: Brain abscess
Pyelo nephritis
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90. ULCER
Is A Break In Continuity Of
Epithelium Due To Necrosis Or
Pathologic Death Of Tissues
Extending Into Submucosa
Common sites are mucosa of mouth, stomach
In acute stage infiltration with polymorphs is seen
In chronic ulcers infiltration by plasma cells,
lymphocytes, macrophages associated with
fibroblastic proliferation
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91. Microbes
Toxins
trauma
ACUTE
INFLAMMATION
RESOLUTION
Clearance of injurious stimuli
, mediators
Replacement of injured cells
Normal function
PROGRESS
HEALING
HEALING
FIBROSIS
Loss of function
LOCALISATION
abscess
HEALING
Chronic inflammation
Angiogenesis
Mononuclear cell
infiltrate
Viral
infections
Persistent injury
Autoimmune
diseases
outcomes
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92. CHRONIC INFLAMMATION
Chronic inflammation is of prolonged
duration(weeks/ months) in which active
inflammation, tissue destruction, and
attempts to repair are proceeding
simultaneously….
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93. CAUSES
1.Persistent infections
By tubercle bacilli, certain virus, fungi
These organisms are of low toxicity
Evoke an immune reaction called
delayed type of hypersensitivity
Leading to formation of a granuloma
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94. Macrophages
Dendritic cells
critical for induction
of t-h cells
IL-
12
IF
IF-Y
ACTIVATES
MACROPHAGES
CAUSE RELEASE
OF PDGF
FIBROSIS
MECHANISM OF TYPE IV HYPERSENSITIVITY IN FORMATION OF
GRANULOMA
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95. • Antigen binding to mannose receptor(mhc) on
surface of macrophage
• This act as antigen presenting cell
• Ag bearing macrophage(icam-1) interacts with
receptor on t-cells(cd11a cd2)
• Helper t cells - MHC CLASS II
• Cytotoxic t cells – MHC CLASS I
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96. 2. Prolonged exposure to potentially toxic agents
Either Exogenous/ Endogenous
Exogenous : Silica when inhaled for prolonged
periods, results in inflammatory lung disease
SILICOSIS
Endogenous : Toxic plasma lipid components lead
to inflammatory process of arterial wall
ATHEROSCLEROSIS
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97. 3. AUTO IMMUNITY
Immune reactions develop against individuals own
tissues
Autoantigens evoke a self perpetuating immune
reaction that results in chronic tissue damage and
inflammation
E.g: Rheumatoid arthritis
Systemic lupus erythematosus
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99. Chronic inflammation is characterised by
1. Infiltration with mononuclear cells which include
macrophages, lymphocytes, plasma cells
2. Tissue destruction induced by persistent offending
agent or by inflammatory cells
3. Attempts at healing by connective tissue
replacement of damaged tissue
accomplished by proliferation of blood
vessels (angiogenesis), fibrosis
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100. Mononuclear cell infiltration
Macrophage is dominant cell in chronic inflammation
It is component of mononuclear phagocyte
system(MPS)
Previously called reticuloendothelial system
Comprises blood monocytes, tissue macrophages
Half life of blood monocyte is about 1day
Tissue macrophage is several months to years
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104. Other cells in chronic inflammation are
Lymphocytes, plasma cells, eosinophils and mast
cells
LYMPHOCYTES are involved in both types of immune
reactions(humoral , cell mediated)
Lymphocytes(B, T) use various adhesion molecules
and chemokines to migrate in to inflammatory sites
Lymphocytes , macrophages interact in a
bidirectional way
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106. Microbial ag should be recognised as non self
This require immunological memory and specificity
This property resides in lymphocytes
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108. EOSINOPHILS
Abundant in immune reactions mediated by IgE
And in parasitic infections
Granules contain major basic protein
A highly cationic protein toxic to parasites
Also causes lysis of mammalian epithelial cells
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109. MAST CELLS
Basophils in tissues
Participate in both acute and chronic
Express on their surface receptors
which bind to Fc portion of IgE
Degranulation cause release of mediators such as
histamine, PAF, eicosanoids, neutral proteases
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110. TYPES OF CHRONIC INFLAMMATION
When injurious agent causes a characteristic
histological tissue response – SPECIFIC
E.g: TB , Leprosy
Histologically characterized by granuloma formation
when irritant produces a non specific inflammatory
reaction with formation of granulation tissue and
healing by fibrosis – NON SPECIFIC
E.g: chronic osteomyelitis , ulcer
Histologically Non specific cell infiltration
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111. GRANULOMATOUS INFLAMMATION
GRANULOMA IS A FOCUS OF CHRONIC
INFLAMMATION CONSISTING OF MICROSCOPIC
AGGREGATION OF MACROPHAGES THAT ARE
TRANSFORMED INTO EPITHELIUM LIKE CELLS
SURROUNDED BY A COLLAR OF MONONUCLEAR
LEUKOCYTES , PRINCIPALLY LYMPHOCYTES ,
OCCASIONAL PLASMA CELLS
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114. Epitheloid cells
They are modified macrophages/
histiocytes which are somewhat elongated, having
pale staining abundant cytoplasm, vesicular, lightly
stained slipper shaped nucleus
Cell membrane of adjacent epitheloid cell is closely
apposed due to hazy outline
They are weakly phagocytic
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115. GIANT CELLS
Formed by fusion of epitheloid cells
May have 20/more nuclei
Nuclei present centrally- FOREIGN BODY TYPE
Nuclei at periphery like horse shoe/ ring/clustered at
two poles- LANGHANS TYPE
They are also weakly phagocytic
Produce secretory products which helps to remove
invading agents
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116. NECROSIS
It is feature of some granulomatous conditions
E.g: caseation necrosis in TB
FIBROSIS
Due to proliferation of fibroblasts at periphery of
granuloma
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117. Factors favouring formation of granuloma
1. Presence of poorly digestible irritant
2. Presence of cell mediated immunity to irritant
implying role of hypersensitivity in granulomatous
inflammation
Types of granuloma
1. FOREIGN BODY GRANULOMA : Material can be
seen in center when viewed with polarised light
2. IMMUNE GRANULOMA : Due to microbes capable
of activating cell mediated immunity
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120. • Temperature > 40C
• Triggers cold receptors
Severe
Inflammation
• Pallor
• A feeling of coldness of skin
surface
Reflex
Vasoconstriction
Of Vessels
RIGOR
Shaking
Exaggerated
shivering which
occurs with a high
fever
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121. Changes in pulse rate
Increase in temperature accompany increase in
pulse
For every 1 degree F rise in temp pulse increase by
10beats/minute
Conversely bradycardia occurs in typhoid fever
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122. Acute phase proteins
Mostly synthesized in liver
Clinical concentration increase 100fold in
inflammation
E.g: CRP, serum amyloid A protein(SAA), Fibrinogen
Cytokines upregulate their synthesis by stimulating
hepatocytes
CRP, SAA acts as opsonins and fix complement
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123. They have beneficial effects in acute inflammation
but in chronic prolonged production leads to
secondary amyloidosis
CRP
Levels increased in infection , inflammation
Tissue necrosis , malignancy , auto immune diseases
It binds to phosphocholine on dead / dying cells and
activate complement
Enhances phagocytosis by microbes
Marked increase indicates risk for CVD , hypertension
diabetes
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124. LEUKOCYTOSIS
Common feature of especially for bacterial infections
Count increase by 15,000 to 20,000cells/cumm
If it increase up to 1lakh – LEUKEMOID REACTION
(but splenomegaly, lymphadenopathy, hemorrhages
are absent)
MYELOID LEUKEMOID
TB, MENINGITIS
ENDOCARDITIS
BURNS
MERCURY POISONING
LYMPHOID LEUKEMOID
INFECTIOUS
MONONUCLEOSIS
TB, PERTUSIS
CHICKEN POX
MEASLES
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125. INITIAL
INCREASE
ACCELERATED
RELEASE OF
CELLS DUE TO
TNF, IL-1
INCREASE IMMATURE
NEUTROPHILS IN
BLOOD
PROLONGED
INFECTION
INCREASED
COLONY
STIMULATING
FACTORS
INCREASED CELLS FOR
COMPENSATION OF
CELL LOSS
LEUKOCYTOSIS
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129. LYMPHANGITIS- LYMPHADENITIS
Lymphatics and lymphnodes that drain the
inflammed tissue show reactive inflammatory
changes
This is a non specific reaction to mediators released
from inflammed tissues
LYMPHANGITIS Inflammation Of Lymphatic Vessels
And Channels
LYMPHADENITIS Inflammation of lymph node
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130. REGULATION OF INFLAMMATION
1. ACUTE PHASE PROTEINS
Alpha 1 anti trypsin:
It Is a Protease Inhibitor
Protects Tissues From Enzymes Of Inflammatory Cells
Especially Neutrophil Elastase
In Absence Degradation Of Elastin
If This Occur In Lungs , This Leads To Respiratory
Problems
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131. Protease inhibitor
Hapatglobin
It Scavangers Hb Released Into Circulation
Potent Antioxidant
Resist Cell Oxidative Stress
Inhibits COX , LOX
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132. 2. CORTICOSTEROIDS
Endogenous glucocorticoids act as anti inflammatory
agents
Their levels are increased in infection , trauma by self
regulating mechanism
3. Supressor T cells / regulator T cells
Modulate immune system
Maintain tolerance to self antigens
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133. 4. Anti inflammatory chemical mediators
propree
RESOLVINS
RvS
OMEGA 3
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135. FACTORS INVOLVING THE ORGANISM
Type of injury and infection
Lung reacts to pneumococci by occurrence of
pneumonia
While it responds to tubercle bacilli by
granulomatous inflammation
Dose
Concentration of organism in small dose form local
lesions
Large dose cause severe spreading infections
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136. Portal Of Entry
Vibrio cholera is not pathogenic if injected sub
cutaneously but cause cholera if swallowed
Product Of Organisms
Certain products cause spread of infection
e.g : streptokinase by streptococci
coagulase by staphylococci
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137. FACTORS INVOLVING THE HOST
1. AGE : very young, very old are less able to combat
infection because of lack of inflammatory response
Many elderly patients respond with a chronic
inflammatory response which in young patients have
provoked acute response
2. DAMAGE TO BONE MARROW AND RETICULO
ENDOTHELIAL SYSTEM
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138. 3. ANTIBIOTIC THERAPY
Antibiotics decrease inflammation because clearing
infection removes reason for inflammation
Inflammatory response is modified depending on
how the agent respond to therapy
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139. 4. Diet
when you eat your body forms PG’s from nutrients
in diet
This can be inflammatory / anti inflammatory
Imbalance in diet leads to formation of
inflammatory PG
On other hand omega-3 fatty acids , antoxidants ,
phyto nutrients can produce anti inflammatory PG
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140. FOODS HIGH
SATURATED FAT
MEAT EGGS DAIRY
PRODUCTS
COFFEE
CONTAINS CRP
PROCESSED MEATS
COOKING FOODS AT
HIGH TEMP
CAUSE RELEASE OF
TOXINS
TRANS FAT
INTAKE OF
PROCESSED FRIED
FOODS
HIGH GLYCEMIC
INDEX CHO
INSULIN CAUSE
METABOLISM OF AA
PRO INFLAMMATORY FOODS
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142. CONCLUSSION
WAR AND INFLAMMATION
Both are stereotyped responses to outside threats
There are specialised troops(immune cells)
Supply routes(vessels)
Communication and intelligence(mediators)
Huge array of lethal weapons(enzymes)
IN WAR AS IN INFLAMMATION THERE IS
DAMAGE TO BOTH ENEMY AND FRIENDLY FORCES
AND SEVERE DAMAGE TO BATTLE FIELD ITSELF
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143. PROBABLY YOUR OWN
DEATH WILL BE CAUSED
BY YOUR LAST
INFLAMMATORY
RESPONSE
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144. References
1. Robbins and Cotran Pathologic Basis
of Disease 7th edition
2. Guyton and Hall Text Book of Medical
Physiology 11th edition
3. Harsh Mohan Text Book of Pathology
5th edition
PRESENTED BY
ANUSHA.V
PG-1ST YEARwww.indiandentalacademy.com
Dynamic process occuring in vascularised vaible tissues……..medico legal distinction between antemortem and postmortem tissues can be made by presence of infl …………
Metchinkoff conducted exp on starfish larva……he implanted foreign material into larva and observed changes in blood cells…..blood cells surrounded foreign body…….from this simple observation he further prog to demonstration of phagocytosis
Lewis named the mediator as h substance……….later it was discovered as histamine…………but antihistamine therapy did not interfere with triple response………indicating that there are substances other than histamine which are involved in infl
LDH: marker of tissue break down
Ldh abundant in rbc: marker of hemolysis: marker in mi( levels peak at 3to4 days n remain elevated upto 10 days
Ldh cause conversion of pyruvate(end product of glycolysis) to lactate in absence of oxygen
In medical infl…..any reaction which is less than 6weeks is acute………..which is greater than 6weeks is chronic
In dental 10 to 12 days is acte………..beyond 12 is chronic
C-cysteine residue…………so 2 cysteine residues seperated by an aminoacid……..
Opsonins coat bacteria they act as signals
When cells are acted upon by diverse stimuli…………they release certain substances……….which act as mediators
Can men……large
WHEN CELL MEMB PHOSPHOLIPIDS ARE PRODUCING ARACHIDONIC ACID………..PAF IS A BYPRODUCT
KALLIKREIN IS A SERINE PROTEASE CAPABLE OF CLEAVING PEPTIDE BONDS
CA—CALCIUM ; PL—PLATELET MEMBRANE PHOSPHOLIPID…….
GENERALLY TISSUE FACTOR IS HIDDEN BY COLLAGEN IN BASEMENT MEMBRANE……DAMAGE CAUSE EXPOSURE OF TF
FIBROSIS: IF INFL OCCURS IN TISSUES WHICH ARE NOT CAPABLE OF REGENERATION OR IF THERE IS MORE PUS WHICH CANNOT BE CLEARED BY INFL CELLS OR IF THERE IS MORE FIBRIN………IT INDUCE CONN.TISSUE FORMATION
THE INABILITY OF AN PREVIOUSLY SENSITISED INDIVIDUAL TO EXPRESS DELAYED TYPE HYPERSENSITIVITY IS CALLED----ANERGY
MOLECULAR MIMICRY: CERTAIN MICROBIAL PEPTIDES THEY RESEMBLE HOST PROTEINS…….
BEST E.G IS AB’S AGAINST BETA HEMOLYTIC STEPTOCOCCI CROSS REACT WITH MYOCARDIAL PROTEINS
B-LYMPHOCYTES –PRODUCED IN BURSA OF FABRISCIUS IN BIRDS
EQUIVALENT IN MAMMALS IS- PEYERS PATCHES IN INTESTINE
But one of law of war is once you enter battle field………..you should kill enemy………..no matter you like it or not…….
Like that if body wants to b healthy it should fight against infections……………by eliciting inflammatory response………..