This document discusses inflammation and its associated processes. It defines inflammation and lists its main causes as infective, immunological, physical, and chemical agents. The document outlines the key features of acute and chronic inflammation, including cardinal signs. It describes the vascular and cellular changes in acute inflammation, focusing on increased vascular permeability and leukocyte migration. The roles of chemical mediators derived from cells and plasma are also summarized. These mediators include histamine, prostaglandins, leukotrienes, cytokines, complement components, coagulation factors, and kinins.

1. INFLAMMATION & REPAIR
-DR.STEPHEN OMEGA BENITTA.M.B.B.S.,

2. DEFINITION:
• Inflammation is denoted by suffix “its”.
• Any injury or infection which causes change in vascularised
connective tissue of the body is called inflammation.
• And mainly consists of responses of blood vessels and leukocytes.
• It brings cells and molecules of host defence from the circulation to
the sites of injury , in order to eliminate the offending agents /
cause.

3. CAUSES:
• The injurious agents causing inflammation may be as under:
• INFECTIVE AGENTS - bacteria , viruses and their toxins ,fungi,
parasites.
• IMMUNOLOGICAL AGENTS- cell-mediated & antigen – antibody
reactions.
• PHYSICAL AGENTS – heat ,cold ,radiation ,mechanical trauma.
• CHEMICAL AGENTS – organic and inorganic poisons.
• INERT MATERIALS – foreign bodies.

4. TYPES:
• On the basis of duration it can be divided into acute(short) or chronic(long).
ACUTE INFLAMMATION CHRONIC INFLAMMATION
ONSET
DURATION
PREDOMINANT
CELLS
LOCAL SIGNS &
SYMPTOMS
CHARACTERISTICS
INJURY /DAMAGE TO
TISSUE & FIBROSIS
Rapid in onset (usually minutes to hour)
Short duration . Lasts for hours or a few days.
NEUTROPHILS
more prominent
Exudation of fluids and plasma proteins (edema)
and the migration of leukocytes.
Usually mild and self limited ; can progress to a
chronic phase.
Slow in onset (days) or may follow acute
inflammation.
Longer duration; may be months.
LYMPHOCYTES, MONOCYTES / MACROPHAGES
ANDSOMETIMES PLASMA CELL.
Less prominent
Inflammatory cells associated with the
proliferation of blood vessels , tissue destruction
& fibroblast proliferation.
Usually severe and progressive with fibrosis and
scar formation.

6. CARDINAL SIGN OF INFLAMMATION:
CARDINAL SIGN MECHANISM
RUBOR (redness) Increased blood flow stasis
CALOR(heat) Increased blood flow
TUMOR( edema / swelling) Increased vascular permeability causing escape of
a protein-rich fluid from blood vessels.
DOLOR(pain) Chemical mediators: prostaglandins & kinins
• The four cardinal signs of inflammation as mentioned by CELSUS
• A fifth clinical sign ,LOSS OF FUNCTION (function laesa) ,was later added
by RUDOLF VIRCHOW.

8. ACUTE INFLAMMATION

9. ACUTE INFLAMMATION:
• Have both vascular changes and cellular changes.
VASCULAR CHANGE IN ACUTE INFLAMMATION:
Vasoconstriction – earliest & transient change in acute inflammation
Vasodilation
Increase vascular permeability (most definitive change in acute
inflammation)
Stasis(VIRCHOW TRIAD)

10. VASOCONSTRICTION:
• 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 re-established in
3-5 seconds
• while with more severe injury the vasoconstriction may last for about
5 minutes.

11. VASODILATION:
• Sometimes it follows a transient constriction of arterioles.
• Vasodilation first affects the arterioles followed by opening of new
capillary beds in the area.
• EFFECT: Result is increased blood flow which causes local warmth and
redness.
• CHEMICAL MEDIATORS: histamine , prostaglandins, platelet activating
factor kinins and nitric oxide(NO)

12. • Progressive vasodilation , in turn ,may elevate the local hydrostatic
pressure resulting in transudation of fluid into the extracellular
space.
• This is responsible for swelling at the local site of acute inflammation.

14. STASIS:
• Slowing or stasis of microcirculation follows which causes increased
concentration of red cells, and thus , raised blood viscosity.
• Stasis or slowing is followed by leucocytic margination or peripheral
orientation of leucocytes (mainly neutrophils) along the vascular
endothelium.
• The leucocytes stick to the vascular endothelium briefly , and then
move and migrate through the gaps between the endothelial cells
into extravascular space.
• The process is known as emigration.

15. PATHOGENESIS:
• The appearance of inflammatory edema due to increased vascular
permeability of microvascular bed is explained on the basis of
Starling’s hypothesis.

16. • According to this ,normally the fluid balance is maintained by two
opposing sets of forces:
 forces that cause outward movement of fluid from microcirculation:
These are intravascular hydrostatic pressure and colloid osmotic
pressure of interstitial fluid .
Forces that cause inward movement of interstitial fluid into circulation;
These are intravascular colloid osmotic pressure and hydrostatic
pressure of interstitial fluid.

18. • Whatever little fluid is left in the interstitial compartment is drained
away by lymphatics and thus, no edema results normally.
• However, in inflamed tissues ,the endothelial lining of
microvasculature becomes more leaky.
• Consequently , intravascular colloid osmotic pressure decreases and
osmotic pressure of the Interstitial fluid increases
• resulting in excessive outward flow of fluid into the interstitial
compartment which is exudative inflammatory edema.

20. INCREASED VASCULAR PREMEABILITY:
a.k.a (VASCULAR LEAK)
• EXUDATION: It is defined as the process of escape of fluid , proteins
and circulating blood cells from the blood vessels into the interstitial
tissue or body cavities.
Escape of a protein-rich fluid causes edema and is one
of the cardinal signs of inflammation.

21. MECHANISM :
• Several mechanisms can increased vascular permeability of
postcapillary venules:
1.Contraction of endothelial cells- most common vascular leak.
2. Direct endothelial injury
3. leukocyte- mediated vascular injury- mainly neutrophils
4. Increased transcytosis
5. Leakage from new blood vessels – (angiogenesis)

22. RESPONES OF LYMPHATIC VESSELS & LYMPH
NODE:
• Apart from blood vessels, lymphatic vessels also participate in acute
inflammation.
• Lymphatic vessels normally drain the quantity of extravascular fluid
that has escaped out of capillaries .
• Increased vascular permeability in inflammation produces
accumulation of fluid in the extravascular space (i.e. edema ).
• In Inflammation ,there is increased flow of lymph that helps to drain
this edema fluid . In addition to fluid ,leukocytes , cell debris , and
microbes, may also flow into lymph .

23. • Secondary inflammation may occur in the draining lymphatics
• Lymphangitis characterized by the presence of red streaks along the
course of the lymphatic channels draining a skin wound
• And also in the draining lymph nodes – lymphadenitis.
• Inflamed draining lymph nodes are often painful and enlarged .
• These lymph nodes are termed as reactive , or inflammatory
lymphadenitis

24. CELLULAR EVENTS / LEUKOCYTIC
• The cellular phase of inflammation consists of 2 processes:
1. Exudation of leucocytes
2. Phagocytosis

25. EXUDATION OF LEUCOCYTES:
• The escape of leucocytes from the lumen of microvasculature to the
interstitial tissue is the most important feature of inflammatory
response.
• In acute inflammation ,polymorphonuclear neutrophils (PMNs)
comprise the first line of body defence , followed later by monocytes
and macrophages .
• The changes leading to migration of leukocytes are as follows;

26. STEPS ARE:
• IN THE VASCULAR LUMEN:
• 1.MARGINATION: when the blood flow slow down (stasis),
leukocytes (mainly neutrophils) move towards the peripheral column
and accumulate along on the endothelial surface of vessels.
• This process of redistribution of leukocyte is termed margination

27. 2.ROLLING:
• Margination leukocytes attach weakly to the endothelium , detach
and bind again with a mild jumping movement.
• It causes rolling of leukocyte along the endothelial surface .
• Molecules involved : selectin family of adhesive molecules and its
complementary ligands.

28. 3.ADHESION:
• Endothelium gets activated and leukocytes bind more firmly .
• Molecules involved : The adhesion /attachment of leukocytes to
endothelial cell is mediated by compensatory adhesion molecules on
these two cell types.
• The expression of adhesive molecules is enhanced by cytokines.
• Integrins with VCAM or ICAM

29. 4.TRANSMIGRATION / DIAPEDESIS:
• Migration of the leukocytes through the endothelium is called
transmigration or diapedesis.
• Leukocytes migrate through the vessel wall by squeezing through
intercellular junctions between the endothelial cells.
• Leukocyte migration occurs mainly in post capillary venules.
• PECAM – 1 or CD 31

31. 5.CHEMOTAXIS:
• Chemotaxis is defined as process of migration of leukocytes toward
the inflammatory stimulus in the direction of the gradient of locally
produced chemoattractants.
• CHEMOATTRACTANTS:
Exogenous : Bacterial products
Endogenous: Cytokines , complement compounds.

32. 6.OPSONISATION:
• Accumulation of leukocytes at the sites of infection and injury:
• Achieved by binding of leukocytes to the extracellular matrix proteins
through integrins and CD44.
• TYPES OF LEUKOCYTES INFILTRATES:
-NEUTROPHILS : predominantly during the first 6-24hrs.
-MONOCYTES : Neutrophils are replaced by monocytes in 24-48hrs.

33. 7.PHAGOCYTOSIS & CLEARANCE :
• It involve killing and destruction of cell.
• STEPS OF PHAGOCYTOSIS:
• Recognition and attachment- Mannose receptor& scavenger receptor
• Engulfment- phagolysosome
• Killing or degradation of the ingested materials- intracellular &
extracellular mechanism.

34. Video….

35. INTRACELLULAR MECHANISM:
1. Oxidative bactericidal mechanism by oxygen free radicals
2. Oxidative bactericidal mechanism by lysosomal granules
3. Non-oxidative bactericidal mechanism.
Intracellular metabolic pathways are involved in killing microbes,
more commonly by oxidative mechanism and less often by non-
oxidative pathways.

36. MECHANISM:
• In the phagocyte vacuole of leukocyte , rapid activation of NADPH
oxidase (also called phagocyte oxidase ), oxidize NADPH to NADP.
During the process oxygen is reduced to superoxide anion(O2-).
• O2- is converted into Hydrogen peroxide (H2O2) by spontaneous
Dismutation.
• O2- +2H  H2O2.

37. • Amount of H2O2 is insufficient to kill most of the microbes by itself but
the enzyme myeloperoxidase (MPO) present in the Azurophilic
granules of neutrophils can convert H2O2 into powerful reactive
oxygen species .
• MPO in the presence of a halide such as Cl- , converts H2O2 to
hypochlorite (HOCL) destroys microbes either by halogenation or by
proteins and lipid peroxidation.
• H2O2 is also converted to hydroxyl radical (OH) which is also powerful
destructive agent.

38. OXIDATIVE BACTERICIDAL MECHANISM BY OXYGEN
FREE RADICALS:
SUPEROXIDE DISMUTASE
H2O2
MYELOPEROXIDASE
HOCL
O2 O2-
NADPH oxidase
Called Respiratory burst process.
NADPH oxidase Deficiency – chronic granulomatous
disease.
(increases infection with pus forming bacteria)
MYELOPEROXIDASE deficiency cause
infection with catalyse +ve & -ve
microbes also candida.

39. OXYGEN INDEPENDENT KILLING:
• By various enzyme and proteins:-
1. Lysozyme – degrade the dead
2. Lactoferrin
3. Major basic protein (found in granules of eosinophills)
4. Defensin – toxic to microbes
5. Bacterial permeability increasing protein

40. CHEMICAL
MEDIATORS OF
INFLAMMATION

41. DEFINITION:
• Substances that initiate and regulate inflammatory reactions are
called as mediators of inflammation.
• Many chemical mediators are responsible for inflammatory reactions.

42. SOURCE OF MEDIATORS :
• Mediators are derived either from cells or from plasma protein.
CELL-DERIVED MEDIATORS PLASMA–DERIVED MEDIATORS
(synthesized mainly in liver )
Histamine
Serotonin
Prostaglandins
Leukotrienes
Platelet- activating factor
Reactive oxygen species
Nitric oxide
Cytokines & chemokines
Complement system
Clotting system
Kinin system

43. CELL DERIVED
MEDIATORS

44. HISTAMINE:
• Produced by Basophils , Platelets ,Mast cells (main source).
• Vasodilator .
• Bronchoconstrictor .
• Increased vascular permeability.
• itching

45. SEROTONIN:
• Produced by Platelets ( main source) and entero-chromaffin cells.
• Vasodilator
• Increased vascular permeability.
• Max. storage in GIT.

46. ARACHIDONIC ACID:
• SOURCE: derived from cell membrane phospholipids mainly by the
enzyme phospholipase A2.
• METABOLISM: Occurs along two major enzymatic pathways.
• These are cyclooxygenase pathway (produce prostaglandins ) and
lipoxygenase pathway (produce leukotrienes and lipoxins)

47. CYCLOOXYGENASE PATHWAY:
PRODUCTS:
• TxA2 : Vasoconstrictor and promotes platelet- aggregation.
• Prostacyclin (PGI2) : Vasodilator and inhibit platelet aggregation
• PGD2 and PGE2 : vasodilation and Increased permeability
SYSTEMIC EFFECTS:
- Prostaglandins are responsible for pain & fever in inflammation.
- PGE2 causes cytokines – induced fever during infection

48. LIPOXYGENASE PATHWAY:
• Leukotrienes
• Lipoxins – Inhibit inflammation.

49. ARACHIDONIC ACID:
PHOSPHOLIPID
ARACHIDONIC ACID
LOX COX

50. CYTOKINES AND CHEMOKINES:
• Function as mediators in immune response and in inflammation.
• Which selectively attracts various leukocytes to the site of inflammation.
• MEDIATORS OF FEVER
• Cytokine IL-1,IL-2 and TNF
• Prostaglandins
• MEDIATORS OF PAIN
• Bradykinin
• Prostaglandins(E2)

51. PLASMA DERIVED
MEDIATORS

52. COMPLEMENT SYSTEM:
• The complement system is a group of plasma proteins synthesized in
the liver, and are numbered C1 to C9.
• PATHWAYS OF COMPLEMENT SYSTEM ACTIVATION:
Step in complement activation is the proteolysis of the third
component, C3.

53. CLEAVAGE OF C3 CAN OCCUR IN ONE OF
THREE PATHWAYS:
1.CLASSIC PATHWAY: It is activated by antigen–antibody (Ag-Ab)
complexes.
2. ALTERNATE PATHWAY: It is triggered by microbial surface
molecules.eg. Cobra venom and other substances, in the absence of
antibody.
3. LECTIN PATHWAY: It directly activates C1

54. FUNCTIONS OF COMPLEMENT:
1. Leukocyte activation , adhesion & chemotaxis
2. Opsonization & promote phagocytosis
3. Cell and bacterial lysis
4. Increased vascular permeability
5. Activation of AA

56. COAGULATING SYSTEM:
• Inflammation and clotting system are intertwined with eachother.
• Activated Hageman factor (factor XIIa ) activate the four systems
involved in the inflammatory response.
1. Activation of fibrinolytic system.
2. Activation of the kinin system .
3. Activation of the alternative complement pathway.
4. Activation of the coagulation system.

58. KININ SYSTEM:
• Kinins are vasoactive peptides derived from plasma proteins.
• Actions of bradykinin:
• Increases vascular permeability
• Pain when injected into skin
• Actions of kallikerein:
• Potent activator of Hageman factor
• Chemotactic activity : directly converts C5 to the chemoattractant
product C5a.

59. MORPHOLOGICAL PATTERNS:
• SEROUS INFLAMMATION:
- Outpouring of a thin serous fluid
- Serous fluid is yellow , straw – like in color and microscopically shows
either few or no cells.
- Eg: skin blister formed in burns or viral infection.

60. FIBRINOUS INFLAMMATION:
• Marked increase in vascular permeability leads to escape of large
molecules like fibrinogen from the lumen of the vessel into the
extravascular space and forms fibrin is called fibrinous exudate.
• A fibrinous exudate is mostly observed with inflammation in the lining
of body cavities, such as the meninges , pericardium , pleura.

61. SUPPURATIVE or PURULENT INFLAMMATION:
ABSCESS
• It is characterized by the production of large amounts of pus or
purulent exudate.
• Microscopically , shows neutrophils , liquefactive necrosis and edema
fluid . Bacteria (eg. staphylococci) which produce localized
suppuration and are called as pyogenic (pus producing bacteria)
• ABSCESS:
• It is the localized collections of purulent inflammatory exudates in a
tissue , an organ or a confined space

62. OUTCOMES OF ACUTE INFLAMMATION:
• Complete resolution with regeneration
• Complete resolution with scarring
• Abscess formation
• Transition to chronic inflammation

63. CHRONIC
INFLAMMATION

64. CHRONIC INFLAMMATION
• CAUSES :
• After acute inflammation
• Persistent infections
• Certain microbe like viruses ,TB ,leprosy ,parasite , fungus.
• Autoimmune diseases
• Foreign materials
• Response to malignant tumor

65. • Here main cells are MACROPHAGES.
• Cells in chronic inflammation are -Macrophages, lymphocytes,
eosinophils , basophils .

66. MACROPHAGES at different places:
• Liver –Kupfer cells
• Bone – Osteoclasts
• Brain – Microglial cells
• Skin – Langerhans cells
• Spleen – Littoral cells
• Placenta – Hof-bauer cells
• Lymph nodes – Sinus histiocytes

67. GAINT CELLS:
• Sometimes multiple macrophages get fused together and form gaint
cells of some disease are
TB - Langhans Gaint cells
Measles – Warthin Finkedlay cells

68. WOUND HEALING

69. TISSUE REPAIR:
• It is basically done by parenchymal cell regeneration & repaired by
connective tissue.
• Different tissues have different regeneration capacities.
• Tissue repair is mediated by various growth factor and cytokines
• Wound contraction is mediated by Myofibroblast.

70. WOUND MAY BE HEALED BY:
• PRIMARY UNION: if less tissue is damaged ,closed by approximation
of wound edges .
• eg: surgical incision
• SECONDARY UNION: If there is large tissue defect , will closed by re-
epithelisation.
• TERTIARY UNION: For very contaminated wound which is initially
debrided and cleaned with antibiotics ,later on close surgically.

71. STAGES:

72. STAGING:
• FIRST 24 HOURS:
• Formation of blood clot – it is formed in the space between sutured
margins. Clot stop bleeding and acts as a scaffold for migrating and
proliferating cells. Dehydration at the external surface of the clot
leads to formation of a scab over the wound.
• Neutrophil infiltration – within 24 hours
• Epithelial changes

73. TWO DAYS:
• Neutrophils are replaced by macrophages .
• The epithelial cells fuse in the midline below the surface scab and
epithelial continuity is re- established in the form of a thin continuous
surface layer.

74. THREE TO SEVEN DAYS:
• Granulation tissue invade incision space .
• It progressively grows into the incision space / wound and fills the
wound area by 5 to 7 days .

75. TEN TO FOURTEEN DAYS :
• Leukocytic infiltration , edema , and angiogenesis disappear during
the second week
• The epithelial proliferation is complete and the wound is weak

76. WEEKS TO MONTHS:
• The scar appears as acellular connective tissue covered by the intact
epidermis and with out inflammatory infiltrate.
• Collogen deposition along the line of stress and wound gradually
achieves maximal 80% of tensile strength of normal skin.

78. WOUND STRENGTH:
• After suturing – 70%
• After removal – 10%
• After 3 months – 70-80%
• 100% healing – NEVER.

79. Thankyou….