Chronic inflammation

Healing and repair

Dr. Mahgoub TagEldeen Osman

2020
Chronic Inflammation
 Definition

Inflammation of prolonged duration

(weeks to years) that most often results
from persistence of an injury-causing agent .
 Causes of chronic
inflammation
 Infection
– Examples-tuberculosis, leprosy, hepatitis C
 Autoimmune disease
– Examples-rheumatoid arthritis, systemic lupus erythematosus
 Sterile agents
– Examples-silica, uric acid, silicone in breast implants
 Cancer:
Chronic inflammatory cells, especially macrophages and T
lymphocytes, may be the morphological expression of an
immune response to malignant cells
 Mechanism of chronic inf

Tissue damage.1

Cytokines infl. 2
Macrophages
fibroblasts

Fibrosis Angiogenesis

Healing.3 Granulation tissue

Histological features
 Mononuclear cells:
– Macrophages
– Lymphocytes/plasma cells
– Fibroblasts
 Necrosis
- Not as prominent a feature as in acute inflammation

- Tissue destruction.
 Evidence of repair: Granulation tissue and
fibrosis
Role of Macrophages

 Functions:
– Phagocytosis.
– Microbial killing.
– Cytokines production.
– Antigen presentation
Formation of granulation tissue
- Highly vascular tissue composed of newly
formed blood vessels (i.e., angiogenesis) and
activated fibroblasts

 Essential
for normal wound healing
 Converted into scar tissue
Granulation tissue
.Types of chronic infl

 Non -specific.

 Specific ( granulomatous):
Granuloma Thick wall

Sinus Ulcer
 Granulomatous inflammation
Specialized type of chronic inflammation
Causes
–Infections
 Examples-tuberculosis and systemic fungal infection (e.g.,
histoplasmosis)
–Noninfectious causes
 Examples-sarcoidosis and Crohn's disease
Cell types
–Epithelioid cells (activated macrophages), mononuclear (round cell)
infiltrate .
–Multinucleated giant cells formed by fusion of epithelioid cells
 Granulomatous inflammation

Granuloma:
collection of macrophage/
epithelioid cells & giant cells ;
surrounded by lymphocytes and
plasma cells with fibroblasts and
collagen.
 Mechanism of granuloma
Injury
Bacterium(TB), fungus , FB

Inability to digest inciting agent

Failure of acute inflammatory

response

Persistent of injurious agent

Cell mediated Sequestration

immune- within
response macrophage
Recruitment of macrophages with
epitheloid and giant cell formation
(Granuloma)
Examples of granulomas

 Tuberculosis
 Syphilis
 Sarcoid
 Tuberculoid leprosy
 Aspergillus granuloma.
 Foreign body granulomas
 Schistosomiasis
Healing, Regeneration and
Repair
 Tissue Repair
•Tissue repair refers to replacement of lost tissue.

•The process involves a complex interaction

among many cell types, matrix proteins, growth
factors, and cytokines, which regulate and
modulate the repair process.

•Outcomes
of injury include Repair and
Regeneration
Repair of tissues involves
two distinct processess
 REGENERATION:
 Replacement by cells of the same type
 Usually no trace of damage

 REPAIR:
Replacement by fibrous/ connective tissue
Scar tissue formation (FIBROSIS)

In most processes BOTH contribute to repair

 The Basic Processes of
Healing

Three key cellular mechanisms are necessary for

:wound healing
Cellular migration

Extracellularmatrix organization,
reorganization, and remodeling

Cell proliferation
Cells that Migrate to the
Wound
•Polymorphonuclear leukocytes
•Macrophages

•Fibroblasts, myofibroblasts, pericytes, and

smooth muscle cells
•Endothelial cells

•Epithelial cells

•Stem cells
 Mechanism of Healing

U RY Soluble Interaction
Y
IN mediators with ECM

Cell migration
Proliferation

Differentiation

Matrix formation

Healing
 Factors Involved in Tissue
Repair
Function(s) Factor
  Growth Factors
Stimulates angiogenesis Vascular endothelial cell growth factor
(VEGF)
Stimulates angiogenesis Basic fibroblast growth factor (BFGF)
Stimulates keratinocyte migration Epidermal growth factor (EGF)
Stimulates granulation tissue formation
Stimulates proliferation of smooth muscle, Platelet-derived growth factor (PDGF)
fibroblasts, endothelial cells
  Hormones
Stimulates synthesis of collagen Insulin growth factor-1 (IGF-1)
Promotes keratinocyte migration
  Interleukins (IL)
Chemotactic for neutrophils   IL-1
 ?To heal OR to repair
 Severity of damage(defect).

 Type of tissue
 TYPES OF TISSUES
Several types of tissue may be identified according to
whether proliferation or function predominates:
Labile tissue:
High regenerative capaility

hemopoietic and lymphopoietic system and cutaneous and

mucosal epithelia

Quiescent tissue:
Highly adaptable,regenerate after cell death
Liver and renal epithelia
Exocrine and endocrine epithelia
Connective and supporting tissue
Smooth muscle cells
Permanent tissue:
•No regenerative capability

Examples: ganglion cells of the central nervous•

system
striated muscle-
CONTROL OF NORMAL CELL
GROWTH
Regeneration (Physiologic and
pathologic )

Physiologic Regeneration
Definition: Replacement of cells or tissues during
the course of normal “wear and tear.”examples:
•Replacement of deciduous teeth by permanent

•dentition.

•Regeneration of the endometrium after

menstruation.
•Epithelium of the intestinal mucosa
Pathologic Regeneration
General definition: Closure of defects caused by
cell injury in a cell system or tissue.
Complete Regeneration
Definition: Generation of new tissue-specific
cells to close a defect and restore the original
tissue architecture.
Incomplete Regeneration
Definition: Closure of tissue defects with by
means of replacement tissue.
Occurrence: wounds and large areas of necrosis.
Wound Healing
 Definition: Closure of a discontinuity in tissue
associated with a loss of substance (wound) by
generation of replacement tissue (initially
granulation tissue, later scar tissue).
 Etiologic factors include:
 trauma (such a cut);
 ischemia (such as an infarction);
 inflammation (such as an abscess).
 Pathogenesis

— Wound results in bleeding.

— Temporary closure is brought about by blood coagulation,
leading to hemostasis.
— Mediators are generated by necrosis at the edge of the
wound. These mediators lead to
— exudation, in which increased vascular permeability
produces a wound exudate and edema at the edge of the
wound, thus cleaning the wound bed. The mediators also
trigger
— chemotaxis , attracting granulocytes and later
macrophages to the site
 Types of Wound Healing
Two types:-
1. By primary intention.
 Clean surgical wound.
 Little damage.
 Pathogenesis :edges of the wound are approximated, the
wound will close directly without formation of granulation
tissue
1. By secondary intention:-
 Large contaminated
 More damage.
 Pathogenesis: a temporary covering of granulation tissue
bridges the defect until it is replaced by scar tissue
 Primary Secondary
intention intention
HEALING BY FIRST
INTENTION
 Immediate: wound fills with a blood clot
 Within 24 hrs: neutrophils at the margin
 24-48 hrs: Epithelial regrowth begins
 Day 3: Macrophages, granulation tissue
 Day 5: Bridging collagen fibres, normal
epidermis
 2nd week: Collegenisation
 End of first month: Cellular connective tissue
 Primary Intention: Steps

Clot formation* Demolition*

Granulation tissue*
Inflammation*
Down growth*
Scar*

Scar Scar off Normal

raised )resolution(
HEALING BY SECOND
INTENTION
 Large tissue defect that must be filled
 Abundant granulation tissue
 Inflammatory reaction more intense
 Contraction

THE TYPE OF WOUND HEALING IS

DETERMINED BY THE NATURE OF THE
WOUND
Secondary Intention: steps

Large clot Granulation tissue

Inflammation Epithelial migration

Blood vessels Permanent scat

fibers Wound contraction
Formation of granulation tissue
- Highly vascular tissue composed of newly
formed blood vessels (i.e., angiogenesis) and
activated fibroblasts

 Essential
for normal wound healing
 Converted into scar tissue
Granulation tissue
Factors delaying healing

Local factors
– Ischemia.
– Infection
– Foreign bodies
– Radiation , movement.
Systemic :factors -
– Malnutrition, deficiency.
– immunity.
– Old age
- Diabetes mellitus.
– Hypercortisolism
Complications of healing

1. Infections
2. Wound adhesion.
3. Keloid formation.
4. Incisional hernia
5. Epidermoid cysts.
Healing and repair

Fracture Healing
Normal Bone
Periosteum

Cortex

Medulla
Medullary cavity

Histology
Anatomy
Clot Demolition Granulation

Inflammation tissue

Gap Remodeling
Calus union
formation
Fracture Healing: Steps

1. Heamatoma.
2. Inflammation / demolition
3. Granulation tissue.
4. Callus formation
5. Union of fracture gap
6. Remodeling
Complications

Early:-
– Bleeding and hypovolemic shock
– Fat embolism
– Avsculer necrosis
– Infections
Late
– Delayed union
– Mal union
– An union
OVERVIEW OF THE
INFLAMMATORY REPARATIVE
RESPONSE