CHRONIC INFLAMMATION

• Inflammation of prolonged duration (weeks or

months).
In which all the following process simultaneously;
 Active inflammation.
 Tissue destruction.
 Attempt at repair.
• Chronic inflammation may follow Acute inflation.
• But may begin insidiously as a low – grade often
asymptomatic response.
• This latter type is the cause of tissue damage in
certain disabling common condition such as ;
  Rheumatoid arthritis.
 Chronic lung diseases.
 Tuberculosis.
Causes of chronic inflammation
• Persistent infection – e.g. TB
• Prolonged exposure to potentially toxic agent e.g.
silica.
• Autoimmunity - immune reaction against
individual’s own tissue e.g Rhaumatoid arthritis.
Mophologic Features
• Chronic inflammation is characterized by;
 infiltration of mononuclear cells includes
macrophages, lymphocytes and plasma cells.
 Tissue destruction
 Induced by persistent of offending agents or
by inflammatory cells.
 Attempt at healing by connective tissue
replacement of damage tissue.
 Accomplished by proliferation of small blood
vessels (angiogenesis) and in particular Fibrosis.
Mononuclear cell infiltration
• The dominant cellular player in chronic
inflammation is macrophage
•A component of mononuclear phagocyte system
(MPS)
• MPs consist of closely related cells of bone marrow
origin
Bone Blood Tissue
Stem cell – monoblast Monocytes – Macrohages microglia(CNS)
half life I day half life month Kupffer cells
- years Alveolar
Activated macrophage
• On reaching tissue monocytes becomes
transformed into larger phagocytic cells called
Macrophages
• Macrophages may be activated by a variety of
stimuli;
 cytokines (e.g. IFN – Y).
 Bacterial endotoxin.
 Other chemical mediators.
• Activation results
 Increase in size of cell
 Increase in level of Lysosomal enzymes
 Greater ability to phogocytose
• Activated Macrophages secrete a wide variety of
biologically active product.
• Some product if unchecked, results in tissue injury
and fibrosis.
• Products of activated Macrophages
 Serve to eliminate injurious agent e.g. microbes.
 Initiate process of repair.
 Are responsible for much of tissue injury in Chronic
inflammation.
• Note some of the products are toxic to microbes
and host cells e.g;
 Oxygen and Nitrogen intermediates some cause influx of
other cells (cytokines and chemotactic factors).
• Other causes fibroblast proliferation and collagen
deposition
• Other agiogenesis
Other cells of Chronic Inflammation
• Lymphocytes
• Plasma cells
• Oesinophils – immune reaction mediated by IgE
e.g Parasitic infection
• Mast cells
 Although neutrophils are characteristic of acute
inflammation chronic inflammation lasting for months
continue to show large numbers of neutrophils .
Granulomatous inflammation
• A distinct pattern of chronic inflammation
• Characterized by focal accumulation of activated macrophages
• The macrophage often develop an epitheliative pattern
(epithelioid cells)
• The aggregate of macrophages is surrounded by a collar of
mononuclear leukocytes;
 Principally lymphocytes and occasionally plasma
cells.
 Old granulomas develops an endosing rim of
fibroblast and connective tissue.
 Frequently epithelioid cells fuse to form giant cells Fuse to
form giant cells
 These giant cells are often in pheriphery but
sometimes in center of granuloma
Giant cells
 Few examples exists in normal tissues.
• Osteoclast – bones.
• Trophoblast – placenta.
• Megakarycytes – Bone Marrow.
 In chronic inflammation when macrophages fails
to deal with particles to be removed, they fuse
together.
• Forms giant cells.
• Giant cells have abundant cytoplasma and multiple
nuclei.
TYPES OF GIANT CELLS
 Foreign body giant cells
 Contains numerous nuclei (upto 100).
 Nuclei size uniform.
 Scattered through cytoplasm.
 Seen as a result of chronic inflammation by foreign
body, also seen in infective granulomas .
 Langharn’s giant cells
 Seen in Tuberculosis and sarcoidosis.
 Nuclei often arranged in pheriphery .
 Forms horseshue pattern.
 Or are clustered in two poles of cells.
 Tuton giant cells
 Multinucleated.
 Vacuolated cytoplasm due to lipoid content.
 Seen e.g. in Xanthoma.
 Aschoff giant cells
 Multinucleated giant cells derived from cardiac
histocytes.
 Seen in rheumatic nodules.
Healing
• Healing process involves 2 distinct
processes(regeneration and repair).
 Regeneration
 This take place by proliferation of
parenchymal cell.
 Usually results into complete restoration of
original tissue.
 Repair
 Take place by proliferation of connective
tissue
 End result is fibrosis and scarring
NB
Both at times take place simultaneously
• Regeneration
Occurs only in when cells are able to
divide postnatally
• Repair
Its replacement of injured tissue by
fibrosis
 Two process involved;
 Granulation formation
 Contraction of wound
 Repair take place by participation of
mesenchymal cells
Fibroblasts, endothelial cells, macrophages, platelets
and parenchymal cells of injured organ
Granulation Tissue formation
 Granulation tissue (‘granular and pink appearance)
• Proliferation of new small vessels
• Proliferation of fibroblast
• New vessels are covered by a thin surface of Fibroblast and
collagen hence pink colour
Contraction of wound
 Achieved by myofibroblasts whose contraction
decreases size of the wound
Regeneration and repair
• Both processes are better demonstrated by
wound healing
• Healing of wound is achieved through the
following two ways ;
 Healing by first intention (primary union)
 Healing by second intention (secondary union)
Healing by first intention
This is defined by wound with the following
characteristics;
 Clean and uninfected
 Surgically incised
 Minimal loss of cells and tissue
Edges approximated by surgical sutures
Sequence of events
1. Initial haemorrhage
Immediately after injury space between filled by
blood.
The blood clot covers the surface preventing
dehydration
and infection.
2. Acute inflammatory response
In 24 hours neutrophils appears from the margin
By third day replaced by macrophages.
• Epithelial changes
• Regeneration
 Basal cells of epidermis of both margin start
 proliferating migrates toward incision al
space “Forms epithelial spurs”.
 As they migrate they lay their basement
membrane
 By 48 hours a well approximated wound is
covered by a layer of epithelium
 Migrated epithelium covers dermis
 Separates if from overlying necrotic material
and clot “scab” which is cast off.
• Basal cells continue to divide.
• By 5th day multilayered new epidermis is formed
(stratified into layers).
REPAIR--Organization
By 3rd day granulation tissue progressively invade
the wound area.
By 5th day Neovascularization is maximal and new
collagen fibrils forming.
• Collagen deposition continues until incision is
bridged.
• By 4th week there is a scar tissue which is scantly
cellular and devoid of inflammatory cells.
Healing by second intention
•Characteristic of wound;
 Open with large tissue defect.
 At times infected.
 Extensive loss of cells and tissue.
 Wound not approximated by suture.
• Healing take place form base upward and from
margin
 Epithelium starts growing from both sides.
 Cannot meet because of large size.
 Large granulation tissue has to form first.
• On healing there is extensive connective tissue
formation.
•End result contraction of wound.
Complication of wound healing
 Infection.
 Defect in scar formation.
 Hypertrophied scar and keloid.
 Excessive contraction.
(contractures).