Sunteți pe pagina 1din 18

Inflammation and Repair

Richard Allcock
S chool of Pathology and Laboratory Medicine, UWA

At this end of this lecture you should be able to :

1. Describe the causes, features and signs of

2. Define the important chemical mediators involved in
inflammatory reactions
3. Describe the different kinds of inflammatory
4. Describe how inflammation resolves and affected
tissues are repaired

Definition and General Features
• Reaction to injurious agents, consisting of
vascular, cellular and systemic responses
• Fluid and cells accumulate at injured site
• Primarily a protective response
• Rapid onset
• Effects mediated by chemical messengers

• Inflammation is tightly controlled

• Sensitive activation
• Massive amplification
• Controlled down-regulation

Signs of Inflammation

Calor Rubor Tumor Dolor

Causes of Acute Inflammation
• Infections and microbial toxins
• bacterial, viral, parasitic
• Trauma
• blunt and penetrating
• Physical and chemical agents
• Burns, frostbite, irradiation, some environmental chemicals)
• Tissue necrosis
• Foreign bodies
• splinters, dirt, sutures
• Immune reactions
• also called hypersensitivity reactions

Steps required for Inflammation
1. Initiating event (ie. a cause)
• Signal to the body that a response is needed
2. A response
• Allow fluid and cells to move out of circulation into the injured site
(what about capillary integrity?)
• At the site, cells must move to the correct area (how?)
• The cells must do something (how do they decide?)
• Send out signals recruiting other cells
• Engulf and attempt to kill and remov e the offending organisms
3. Down-regulation of the response when finished
• Short-lived responses that only continues whilst needed
• Require s continual re-stimulation

Movement of Cellular and Vascular


What can cells do when they reach
1. Phagocytosis
• Engulfment and removal of organisms/foreign
2. Activation
• Direct lysis and killing of foreign organisms
3. Release mediators
• Can attract more cells to the area or activate cells
already present

Overview of Phagocytosis

Macrophage adhering to E. Coli

Leukocyte activation

• Leukocytes generally indiscriminate

• Self-preservation
• Require activation in order to do anything

• Acti vation results from signals delivered from the cell

• Many different receptor pathways
• Many possibilities………….
• Arachidonic acid metabolite production
• Cy tokine secretion
• Modulation of adhesion molecules
• Phagocy tosis f ollowed by degranulation and secretion of lysosomal
enzy mes

Sources of inflammatory mediators
• Cell-derived
• Act alone, active when secreted

• Plasma Mediators
• Act in interacting cascades, require activation

Possible Courses of Acute Inflammation

• Different stimuli cause different courses of

inflammation, which will then resolve differently
• Purulent Inflammation (suppurative)
• Fibrinous Inflammation
• Serous Inflammation
• Ulcerative Inflammation
• Most mediators have v. short half-lives
• Degrade quickly, so inflammation persists as long as
stimulus persists

Purulent Inflammation
• Pus = dead white cells/bacteria. Creamy–yellow colour.
• Pyogenic bacteria (eg. Staph spp.) result in purulent
• Purulent inflammation characterised by :
• Large amounts of pus
• Large amounts of neutrophils, necrotic cells, edema fluid
• Abscesses : collection of purulent inflammatory tissue in
confined space (or deep within tissues)
• Central region w/ mass of necrotic cells
• Preserved zone of neutrophils
• Vascular dilation and fibroblast proliferation - ?Repair?
• ?Fibrotic wall?

Subcutaneous bacterial abscess

Fibrinous Inflammation
• Severe injury causes greatest vascular permeability
• Fibrinogen enters tissues, is cleaved to form fibrin
• Eg. Inflammation of lining of meninges, pericardium
• Fibrin can be broken down and removed (resolution)
• When not removed, can lead to scarring. Functional

Serous Inflammation

• Thin fluid from plasma or mesothelial cells in

peritoneal, pleural and pericardial cavities
• Eg. Blisters from burns or viral infections

Ulcerous Inflammation
• Excavation in tissue surface produced by
shedding of necrotic inflammatory tissue
• Mucosa of mouth, stomach, intestines, or
genitourinary tract
• Lower extremities of individuals with impaired

Complete Resolution of Inflammation

• 1. Return to normal
• 2. Drainage of fluid and
proteins into lymph
• 3. Pinocytosis into
• 4. Phagocytosis of apoptotic
• 5. Phagocytosis of necrotic
• 6. Disposal of macrophages

Consequences of Too Much or Too

Little Inflammation

• Defective inflammation
• Inc. susceptibility to infections
• Delayed wound healing and repair

• Excessive inflammation
• Excessive tissue damage
• ??Death to the host??

Diseases Associated with Inflammation
Acute Chronic

Acute respiratory distress syndrome Arthritis

Acute transplant rejection Asthma

Asthma Atherosclerosis

Glomerulonephritis Chronic lung disease

Reperf usion injury Chronic rejection

Septic shock


Genetic defects identified in almost all stages of inflammatory pathway

General Comments on healing

• Inflammation and healing/regeneration occur

• Integrated response of many cell types (cf.
• Numerous chemical mediators and growth
factors involved
• New tissues must be formed
• The newly formed tissue has to become
vascularised – angiogenesis

Overview of Healing
• Fibroproliferative response that patches areas of
damaged tissue

1. Inflammation to remove damaged and dead tissue

2. Entry and proliferation of CT and parenchymal cells
3. Formation of new blood vessels
4. Synthesis of new ECM proteins
5. Tissue remodelling
6. Wound contraction
7. Acquisition of wound strength

Factors Affecting Healing
• Injury-related factors
• Nature of the tissue, nature of the injury, intensity of the
stimulus, duration of the stimulus
• Inflammatory factors
• Foreign bodies, Inadequate vascularisation,
denervation, mechanical stress, necrotic tissue,
dressings, surgical techniques
• Host factors
• Age, anemia, drugs, genetic disorders, hormones,
diabetes, malnutrition, obesity, systemic infection,
temperature, trauma, uremia, vitamin deficiency, trace
metal deficiencies

Formation of Scars 1 :
Migration & Proliferation of Fibroblasts
• “Granulation tissue” can start forming <24hrs after
• Vascular endothelial cells and fibroblasts
• Macroscopic – soft, pink, granular
• Microscopic – angiogenesis and fibroblast proliferation
• New vessels leaky, so tissue edematous
• Fibroinogen and plasma fibronectin form early stroma
• Fibroblasts attracted by TGFβ, PDGF, EGF, FGF,
IL1 and TNF
• Mφ are a source of GFs,
• Also clear debris, fibrin and foreign material from site

Formation of Scars 2 :
ECM Deposition

• Fibroblasts major source of ECM components

• Collagen synthesis starts 3-5 days after injury
• Collagen deposition depends on synthesis and
• Granulation tissue becomes the scar
• Spindle-shaped fibroblasts
• Dense collagen
• Elastic tissue fragments
• Vascular regression leads to scar becoming pale


Prior to healing After healing

Healing by First and Second Intention

• Deficient scar formation
• Mechanical stress or inadequate vascularisation
• Can cause rupture and/or ulceration
• Excessive formation of repair components
• Excess collagen causes raised scars (hypertrophic)
• Scar beyond original boundaries = keloid
• Contractures
• Too much contraction deforms the surrounding tissue