Lecture 4

Inflammation and Repair

Overview of tissue responses

to injury
Tissue damaged : cells
die
Acute inflammation

Damaging stimulus
removed
Cells can
Cells cannot
regrow
regrow
Regeneration
Healing by
repair

Damaging stimulus
persists
Chronic
inflammation
Persistent
No

Restoration
of normal
structure
and function

Scar
formation: loss
of specialized

Damaging agent
removed?
Yes

Inflammation
Bodys mechanism against damaging agents
Non-specific immune response
Purposes are for:
Clear away dead tissues
Protect against local infection
Allow immune system access to the damaged area
Isolate, neutralize and remove cause
Initiate healing process

Either acute or chronic

Acute inflammation vs chronic

inflammation
Acute

Chronic

Rapid onset
Lasts for minutes to
days
Characterized by
exudation of fluid and
protein from vessels
and emigration of
neutrophils
Results in repair
mechanism

Longer time course

9days to years)
Involves different cell
types (lymphocytes
and macrophages)
Tissue repair coexist
with tissue destruction

Acute inflammation
Cardinal signs: rubor (red discoloration), calor
(heat), dolor (pain), tumor (swelling) and loss of
function
Causes include: infection, trauma, physical and
chemical agents, necrosis, foreign bodies and
immune reactions
Main functions:
1. Mediates local defenses presence of acute
inflammatory exudate containing protein, fluid and cells
2. Destroys infective causative agents (if presence)
3. Removes debris from damaged tissue

 Stages:
1. vasodilation,
2. increased vascular permeability,
3. WBC emigration

Main groups of mediators

involved in acute inflammation
Cellular mediators of acute inflammation
Stored

Active synthesis

Histamine

Prostaglandins, leukotirnes,
platelet activating factor,
cytokines, NO, chemokines

Plasma-derived mediators of acute inflammation

Kinin system

Bradykinin

Clotting pathway

Activated Hageman factor

Thrombolytic system

Plasmin

Complement pathway

C3a, C3b, C5a

Morphology of acute
inflammation
Types of acute inflammation include:

Appearanc
e

Serous

Fibrinous

Purulent

Relative clear,
watery fluid

Finely
Pus (thick,
particulate, thick white-yellow
fluid
fluid)

Contents of Few cells, most

fluid
inflammation is
fluid

Much more
protein and cells

Neutrophils,
protein and
necrotic cells

Seen in

Uremic and
postmyocardial
infarct
pericarditis

Bacterial and
fungal infections

Viral infections
and burns

Outcomes of acute inflammation

Basic
description

Requirements

Important
points

Resolution

Inciting agent is
removed, all
damages are
repaired

Organ is capable
of regenerate

Intact basement
membrane and
organ framework

Abscess

Walled of
collection of pus

Body cannot rid off Any organ

the agent or repair
and scarring occur
faster at tissue
around the
abscess

Ulcer

Loss of mucosa
and deeper tissue.

Body cannot
remove agent

GIT

Fistula

Anomalous patent
connection
between two
organs

Inflammation
involves full
thickness of wall
of organ, duct or
blood vessel

Inflammatory
bowel disease

Replacement of
tissue parenchyma

Loss of tissue in
orga incapable of

Chronic
inflammation
Scar formation

Chronic inflammation
Prolonged inflammation consisting of active
inflammation and tissue destruction and repair
Can occur following acute inflammation and also
as a low-grade, asymptomatic, prolonged
response to damaging agent
Causes: viral, persistent microbial infection,
prolonged exposure to toxin and autoimmune
dysfunction
Cells involved: macrophages and lymphocytes
Example: granulomatous (e.g.tuberculosis,
sarcoidosis)
Collection of epitheloid histiocytes, with presence of
multinucleated giant cells caused by mycobacteria, fungi,
foreign material, sarcoidosis and silica

Systemic effects of
inflammation
Pyrexia: increased in body temperature induced
by pyrogens stimulated by phagocytosis,
endotoxins and immune complexes
Constitutional symptoms: malaise, anorexia,
nausea
Weight loss: negative nitrogen balance
Reactive hyperplasia of reticulo-endothelial
system
Haematological changes: increased ESR,
leukocytosis, anaemia
Amyloidosis

HEALING AND REPAIR

Repair:
Involves regeneration of the parenchyma or replacement
of damaged tissue with a scar if regeneration is not
possible

Regeneration:
A complete replacement of damaged cells with no scar
formation
Can occur in renewing tissues (GIT and skin)
Can occur in stable tissues
Requires intact connective tissue scaffold

Healing:
Regeneration of cells combined with scarring and fibrosis

 Components of healing

Induction of inflammatory process

Formation of new blood vessels
Production of extracellular matrix including collagen
Tissue remodelling
Wound contracture
Increasing wound strength

 Replacement by scar involves these processes:

Angiogenesis
Migration and proliferation of fibroblasts
Deposition of extracellular matrix
Maturation and reorganization of fibrous tissue

Scar formation starts within 24 hours of onset of

acute inflammation
After 3 5 days: granulation tissue is formed
In week 2: deposition of collagen occur. No edema and
inflammatory cells
In 1 month: no inflammatory infiltrate, scar consists of
collagen

Factors that affect wound

healing
General factors include: infections, nutritional
deficiency, glucocorticoid therapy
Mechanical factors: unintentional reopening of
wound
Poor perfusion: decrease blood supply

 Complications of healing by scar formation

Loss of function
Contractures and obstructions
Results in deformity of joint which restrict joint
movement (contracture)
Shrinkage of scar tissue may cause stenosis

Adhesions
Prevent normal movement of the structures and may
distorts the tissue

Hypertrophic scar tissue (e.g. keloid)

Ulceration
Due to impaired blood supply