Chronic inflammation is characterized by prolonged inflammation lasting weeks or months, where inflammation, tissue injury, and repair occur simultaneously. It is caused by persistent infections, immune-mediated diseases, or toxic agents. Chronic inflammation involves infiltration of mononuclear cells like macrophages and lymphocytes, ongoing tissue destruction, and attempts at repair through fibrosis and angiogenesis. Macrophages play a key role by secreting cytokines and growth factors that mediate both inflammatory tissue injury and repair.

1. Chronic
Inflammation
Chronic inflammation is inflammation
of prolonged duration
(weeks or months)
in which
inflammation, tissue injury, and attempts at repair
coexist, in varying combinations.

2. CAUSES OF CHRONIC
INFLAMMATION
1.Persistent Infection
2.Immune-mediate &
inflammatory diseases
3.Toxic Agents/FOREIGN BODY

3. • DOES SURGERY ASSOCIATED WITH CHRONIC
INFLAMMATION
• YES
• HOW COME?
• SUTURE MATERIAL

4. GENERAL FEATURES

5. • MONONUCLEAR CELL INFILTRATION
• TISSUE DESTRUCTION//NECROSIS
• PROLIFERATIVE CHANGES
FIBROSIS ANGIOGENESIS

6. • CHRONIC INFLAMMATION ALWAYS ATTEMPTS
TO HEALING

7. FEATURES
Chronic inflammation is characterized by:
1. Infiltration with mononuclear cells, which include
macrophages, lymphocytes, and plasma cells
2. Tissue destruction, induced by the persistent
offending agent or by the inflammatory cells
3. Attempts at healing by connective tissue
replacement of damaged tissue, accomplished by
proliferation of small blood vessels (angiogenesis)
and, in particular, fibrosis.

9. • WHAT IS THE KEY PLAYER IN CHRONIC
INFLAMMATION??

10. • MACROPHAGE

11. • DOES MACROPHAGE DIRECTLY COMES TO
CHRONIC INFLAMMATION
• NO

12. • MONOCYTE
• MACROPHAGE

14. WHAT ARE THE PRODUCTS
SECRETED BY MACROPHAGES??

15. • CYTOKINES-IL1, IL-2
• INTERFERONS –Y
• GROWTH FACTORS- TGF, PDGF, FGF,EGF
• [TGF, PDGF------- to stimulate fibroblast]
• COMPLEMENT FACTORS[C]
• ENZYMES—Proteases, endonucleases,
elastases

16. • Chemotactic factors
• NO
• Collagenases

17. • ANY OTHER??
• LYMPHOKINES

18. • IS NORMAL LYMPHOCYTE SECRETES
LYMPHOKINES??
• CD4 Lymphocytes[[Th cells]

21. THE ROLES OF ACTIVATED
MACROPHAGES IN CHRONIC
INFLAMMATION :
1.Inflammatory Tissue Injury
2.Repair (Growth Factor Mediated)
Fig 2-24 (p72)

22. MACROPHAGE-LYMPHOCYTE
INTERACTIONS IN CHRONIC
INFLAMMATION :
Fig 2-25
(p73)

24. TYPES

27. GRANULOMATOUS
INFLAMMATION
Granulomatous inflammation is a distinctive pattern
of chronic inflammation that is encountered in a
limited number of infectious and some
noninfectious conditions. Immune reactions are
usually involved in the development of
granulomas.
A granuloma is a cellular attempt to control an
offending agent that is difficult to eradicate.
.

28. • In this attempt there is often strong
activation of T lymphocytes leading to
macrophage activation, which can cause
injury to normal tissues

29. A granuloma is a focus of chronic
inflammation consisting of
a microscopic aggregation of
macrophages
that are transformed into epithelium-
like cells, surrounded by a collar of
mononuclear leukocytes, principally
lymphocytes and occasionally
plasma cells.

34. Types of
Granulomas
I. Foreign body granulomas
II. Immune granulomas

35. Foreign body granulomas
Incited by relatively inert foreign bodies.
Typically, foreign body granulomas form around
material that are large enough to preclude
phagocytosis by a single macrophage and do not
incite any specific inflammatory or immune
response.
.

37. Immune granulomas
Caused by agents that are capable
of inducing an immune response
which produces granulomas
usually when the inciting agent is
poorly degradable or particulate.

44. Giant
Cells
Older granulomas develop an enclosing rim of
fibroblasts and connective tissue.
Frequently, epithelioid cells fuse to form giant cells
in the periphery or sometimes in the center of
granulomas.
These giant cells may attain diameters of 40 to 50
μm.
peripherally (Langhans-type giant cell) or
haphazardly (foreign body–type giant cell).

47. • WHAT IS THE SHAPE OF EPITHELOID CELL
• ‘SOLE SHAPE’

48. SYSTEMIC EFFECTS OF CHRONIC
INFLAMMATION

49. • Chronic inflammation is associated with following systemic
features:
• 1.Fever. Invariably there is mild fever, often with loss
of weight and weakness.
2.Anaemia:chronic inflammation is accompanied by
anaemia of varying degree.
3.Leucocytosis. As in acute inflammation, chronic
inflammation also has leucocytosis but generally there
is relative lymphocytosis in these cases.
4.ESR. ESR is elevated in all cases of chronic
inflammation.
•
•
•

50. • Which of the following is always present in
chronic inflammation/
• A. Rubor
• B. Edema
• C. Leucocytosis
• D. Increased ESR

51. MORPHOLOGY

56. • DRAW A NEAT LABELLED DIAGRAM OF
GRANULOMA
• PATHOGENSIS OF GRANULOMA
• DIFFERENCE BETWEEN ACUTE &CHRONIC
INFLAMMATION

58. • Tissue repair: restoration of tissue architecture and function after
an injury
• Occurs in two ways:
• Regeneration of injured tissue.
• Replacement by connective tissue (scarring)

59. • Usually, tissue repair involves both processes
• Involves cell proliferation, and interaction between cells and
extracellular matrix.

60. • Many cells proliferate during tissue repair:
• Injured tissue remnants.
• Vascular endothelial cells
• Fibroblasts

61. Tissues of the body are divided into three
groups:
•Continuously dividing (labile) tissues.
•Stable tissues.
•Permanent tissues

62. •Continuously dividing (labile) tissues
•Cells are continuously proliferating.
•Can easily regenerate after injury
•Contain a pool of stem cells
•Examples: bone marrow, skin, GIT epithelium.

63. Stem cells in
skin

64. Stem cells in GI
epithelium

65. •Stable tissues
•Cells have limited ability to proliferate.
•Limited ability to regenerate (except liver!)
•Normally in G0, but can proliferate if injured.
•Examples: liver, kidney, pancreas…

66. • Permeant tissue
• Cells can't proliferate
• Can't regenerate (So injury always lead to scar)
• Examples: Neurons, Cardiac muscles

67. GROWTH
FACTORS
•Very important in tissue repair.
•Actions:
•Stimulate cell division and proliferation.
•Promote cell survival.

68. THE EXTRACELLULAR
MATRIX
•ECM is the network that surrounds cells. It is two forms: interstitial
matrix and basement membrane.
•ECM regulates proliferation, movement, and differentiation of the
cells living in it.

69. REGENERATI
ON
Occurs all the time in labile tissues
Cells are constantly being lost and replaced
If demand increases, supply increases easily

70. •Occurs in limited form in stable tissues
•Remove one kidney: the other one undergoes hypertrophy and
hyperplasia
•Remove half of the liver: it will grow back

71. SCARRI
NG
•If injury is severe, regeneration can’t happen
•So, fibrosis (a scar) replaces the injured tissue

72. •Four components to this process:
•New vessel formation (Angiogenesis).
•Fibroblast proliferation.
•Synthesis of collagen (Scar
formation).
•Remodeling of the scar.

73. •By 24 hours:
•Endothelial cells start proliferating
•Fibroblasts emigrate
•By 3-5 days:
•Granulation tissue present (blood vessels+ fibroblasts).
•Weeks later:
•Dense fibrosis (scar)
•Scar is remodeled over time

76. Introduction to wound
healing
• Healing is a complex and dynamic process of restoring cellular structures
and tissue layers.
• The adult wound healing process can be divided into 4 distinct phases:
• The homeostasis phase
• the inflammatory phase
• the proliferative phase
• the remodeling phase.

77. Sequence of events in
healing
Initial phase - Hemostasis
• Following vasoconstriction,
endothelium and discharge
platelets
adenosine
adhere to
diphosphate
damaged
(ADP),
promoting thrombocyte clumping, which dams the Wound

78. • The inflammatory phase is initiated by the release of numerous
cytokines by platelets.
• Fibrinogen is cleaved into fibrin and the framework for
completion of the coagulation process is formed.

79. Second phase - Inflammation
• Within the first 6-8 hours
• polymorph nuclear leukocytes (PMNs) “cleanse” the wound, clearing it of
debris , monocytes also exude from the vessels. These are termed
macrophages. The macrophages continue the cleansing process and
manufacture various growth factors during days 3-4.

80. Third phase -
Granulation
sub phases are: fibroplasia - matrix deposition - angiogenesis -
and re-epithelialization
• In days 5- 7, fibroblasts have migrated into the wound, laying
down new collagen of the subtypes I and III

81. • Angiogenesis . The formation of new vasculature requires
migration, mitosis, and maturation of endothelial cells
• Re-epithelization occurs with the migration of cells from the
periphery of the wound . Division of peripheral cells occurs in
hours 48-72, resulting in a thin epithelial cell layer, which bridges
the wound.

82. Fourth phase - Remodeling After the third week, the wound
undergoes constant alterations, known as remodeling,
• This can last for years after the initial injury occurred. Collagen
is degraded and deposited in an equilibrium-producing fashion

83. • Contraction of the wound is an ongoing process resulting in part
from the proliferation of the specialized fibroblasts termed
myofibroblasts, which resemble contractile smooth muscle cells.

84. 1. SKIN WOUND
HEALING
• First intention
• Second intention

86. Healing by First Intention
•Occurs in small wounds that close easily
•Epithelial regeneration predominates over fibrosis
•Healing is fast, with minimal scarring/infection
•Example: Well-approximated surgical incisions

87. Healing by First Intention: Timeline
• By 24 hours
• Clot forms
• Neutrophils come in
• Epithelium begins to regenerate

88. • By 3-7 days
• Macrophages come in
• Granulation tissue is formed
 New blood vessels
 Fibroblasts
• Collagen begins to bridge incision
• Epithelium increases in thickness

89. • Weeks later
• Granulation tissue gone
• Collagen is remodeled
• Epidermis is full and mature, but without dermal
appendages.

93. Healing by Second Intention
• Occurs in larger wounds that have gaps between wound margins
• Fibrosis predominates over epithelial regeneration
• Healing is slower, with more inflammation and granulation tissue
formation, and more scarring

94. • Examples:
• Myocardial Infarction
• Large burns and ulcers

97. Skin ulcer: large gap between edges

98. FACTORS AFFECTING WOUND HEALING
Local factors
• Infection is the single most important cause of delay in healing.
• Mechanical factors, as early motion of wounds, can delay healing.
• Foreign bodies, such as fragments of steel, glass, or even bone

99. • Size, location, and type of wound influence healing. Wounds in
richly vascularized areas, such as the face, heal faster than those in
poorly vascularized

100. General Factors
• Age
• General state of health
• chronic diseases e.g. diabetes, rheumatoid arthritis etc.
• Drugs (steroids) and hormones
• General cardiovascular status

101. • General dietary deficiencies e.g. protein
• Specific dietary deficiencies
• Vitamin C
• sulphur-containing amino acids

102. Complications of Repair
• Insufficient fibrosis:
• hernia; ulceration
• Excessive fibrosis:
• Cosmetic scarring; hypertrophic scars; keloid

103. • Excessive contraction:
• Limitation of joint movement (Contractures); obstruction of tubes
& channels (Strictures)

104. Keloid scar