Healing and Repair

Repair/Healing
• Healing is the body response to injury so that normal
structure and function are restored
• Resolution – romoval of debris with inflammatory
response
• Regeneration –proliferation of parenchymal cells such
that complete restoration of original tissues occurs
• Repair by scar [organization] – when there is tissue loss
- healing by proliferation of connective tissue resulting in
fibrosis and scar formation
• At times both occur together
 Injury

Cellular and vascular response

Stimulus removed
)acute injury( Persistent tissue damage

Parenchymal cell death Parenchymal cell death

(intact tissue framework) (damaged tissue framework)
Superficial wounds Deep wounds
Some inflammatory processes

HEALING
REGENERATION FIBROSIS
Scar formation
)Restitution of normal structure ( )Tissue scar(
Organisation of exudate

Examples
Liver regeneration after partial Examples Examples
Hepatectomy Deep excisional wounds Chronic inflammatory diseases
Superficial skin wounds Myocardium infarction (cirrhosis, chronic pancreatitis,
Resorption of exudate in lobar Pulmonary fibrosis)
pneumonia
 Tissue Repair Mechanisms
Cell Renewal
• Whether regeneration or fibrosis is
dependent upon the regenerative ability of
the cells/organ involved.
• Capability of cells to
replicate
• Tissue Type
- Labile
- Stable
- Permanent
 Tissue Repair Mechanisms
Cell Renewal
• Whether regeneration or fibrosis is dependent
upon the regenerative ability of the cells/organ
involved.
• Ability to replace complex structures such as renal
glomeruli
• Stem cells pool in labile and
stable population
• Minority population located
epidermis - basal layer adjacent to BM
intestine - bottom of crypts
 Labile Cells
• Continuously dividing
• Regenerate from a population
of stem cells after injury
• >1.5% cells in mitoses
• Examples
- Cells in contact with environment-epidermis,
alimentary tract, respiratory tract, urinary tract,
vagina, cervix, uterus
- Lymphoid Cells – lymph node, spleen
- Haematopoietic Cells
 Stable Cells
• Low level of replication
- < 1.5% of normal adult cells are
in mitoses
• Can respond to stimuli
• Examples
1. organs- liver, kidney,
pancreas, adrenals, thyroid
– Need intact basement
membrane eg. renal tubules
can regenerate- Glomeruli do
not
regenerate
– 2. vascular endothelium
– 3. bone
– 4. cartilage cells
– 5. Mesenchymal cells
• Smooth muscle cells
• Fibroblasts
 Permanent Cells

• Cells don’t divide

• No regenerative ability
• 0.0% cells are in mitoses
• Examples
– Neurons
– Lens epithelium
– Cardiac myocytes
– Skeletal muscle cells
 Complete Restitution
• Loss of labile population eg.
skin abrasion
• Cells at margin proliferate to
cover defect
• Spread as a thin sheet till
defect covered
• When form confluent layer -
contact inhibition
• Epidermis then rebuilt from
base upwards
• Ability of adnexal glands to
regenerate - used in plastic
surgery
 Stimulus removed
)acute injury(

Parenchymal cell death Parenchymal cell death

(intact tissue framework) (damaged tissue framework)
Superficial wounds Deep wounds
Some inflammatory processes

HEALING
REGENERATION Scar formation
)Restitution of normal structure( Organisation of exudate

Examples
Examples
Liver regeneration after partial
Deep excisional wounds
Hepatectomy
Myocardium infarction
Superficial skin wounds
Resorption of exudate in lobar
pneumonia
 Wound Healing -organisation
• Two Processes
1.-Granulation tissue formation with removal
of dead tissue by phagocytosis
2.-Contraction of wound
• Cells involved – organ injured
- mesenchymal cells
- connective tissue stem cells
- fibrocytes
- histiocytes
- endothelial cells
- macrophages,
 Formation of Granulation tissue
• Phase of inflammation
• Phase of clearance
• Ingrowth of granulation tissue
- Angiogenesis (neovascularisation)
comprises of loops of capillaries supported
by myofibroblasts.
-Actively contracts to reduce wound
size which may result in a stricture later -
Fibrogenesis
 GRANULATION TISSUE
• The term granulation
tissue derives from its
pink, soft, granular
appearance on the
surface of wounds.
• Proliferation of new
small blood vessels and
fibroblasts are its
characteristic histological
features.
 Angiogenesis

• Proteolysis of ECM
• Migration and chemotaxis
• Proliferation
• Lumen formation ,
maturation and inhibition
of growth
• Increased permeability
through gaps and
transcytosis
 Repair by -
fibrosis
• 1. Angiogenesis
• 2. Migration and
proliferation of fibroblasts
• 3. Deposition of Extra
Cellular Matrix
• 4. Maturation and
reorganization
- Granulation bed contracts
as it matures
- Myofibroblasts
(actomyosin) act as
contractile cells
 Wound contraction and scarring

• Reduce volume of repair tissue

• Begins in 2-3 days and completes by 14th day
• Result of contraction of myofibroblasts in granulation
tissue.
• Retracts as a whole and brings together surrounding
tissue.
• Collagen secreted at same
time forms a local scar
• tho useful can produce defects
– Stenosis/stricture intestine
– Permanent contractions
– burns
 Factors favoring Fibrosis over
regeneration
• Severe and prolonged tissue injury
• Loss of tissue framework (basement
membranes)
• Large amounts of exudate
• Lack of renewable cell populations
• Consequences
• Loss of functional parenchymal tissue
• Skin with scar is more prone to tearing
 Organisation

• Process by which specialised tissues repaired by formation of mature

fibrovascular connective tissue
• Granulation tissue – early
• Dead tissue removed by macrophage
• Granulation tissue contracts – scar forms which then undergoes remodelling
eg. -Infarct
 MI 18-24 hr loss of
nucleus, contaction bands,
coagulative necrosis

MI 3-4 day –
Hemorrhage,
inflammation.
MI 1-2w – Granulation tissue

MI 2-4 W - Resorption, fibrosis

MI >4-6 W - Collagen Scar

Infarct kidney – healing by fibrosis
 Stimulus removed
)acute injury(

Parenchymal cell death Parenchymal cell death

(intact tissue framework) (damaged tissue framework)
Superficial wounds Deep wounds
Some inflammatory processes

HEALING
REGENERATION Scar formation
)Restitution of normal structure( Organisation of exudate

Examples
Examples
Liver regeneration after partial
Deep excisional wounds
Hepatectomy
Myocardium infarction
Superficial skin wounds
Resorption of exudate in lobar
pneumonia
 Wound Healing - SKIN
• Classic example of regeneration and repair
• Healing by first intention (minimal necrosis &
inflammation) – primary union
- clean
- not infected
- surgically incised
- little loss of tissue
- tissue elements close
to one another
• Healing by second intention
–secondary union (extensive necrosis & inflammation)
 Healing by First Intention

• Example: surgical wound

• Result: healing with like tissue

and little scar formation (fibrosis)

• Epithelial regeneration
predominates over fibrosis

• 24 hours
- Neutrophils migrate into
fibrin clot
- Basal cells at edges
- Increase mitotic activity
 Healing by First Intention
Wound healing
• 24 – 48 hours
Epithelial cells migrate and
proliferate
- Deposition of basement
membrane
• Days 3 - 7
- Macrophages replace
neutrophils
- Neovascularization
- Granulation tissue
- More collagen bundles
- Bridging of wound
- Epithelial cells continue
to proliferate
 Healing by First Intention
Wound Healing
• Week 2 ( day 14)
Collagen accumulation continues
to increase
- Fibroblast proliferation
- WBC and edema decreases
- Vascular channels regress
- Blanching

• 4 weeks
- scar formed by fibroblasts and
collagen
- Few inflammatory cells
- Tensile strength increases
Healing by Second Intention
Wound Healing
• Injury more extensive –tissue
loss excessive
- More inflammation
- More fibrin
- More granulation tissue
- More complex
repair process
- wound contracts
 Healing by second intention

• Response characterised by
- phagocytosis to remove debris
- granulation tissue to fill defect
- repair specialised tissue loss
- epithelial regeneration to cover gap

• Time scale will depend on volume of defect

• Final cosmetic result will depend on quantum of tissue

loss and scarring
 Complications of wound healing
• Infection
• Implantation(epidermal inclusion ) cyst
• Pigmentation
• Weak scar
• Incisional hernia
• Keloid formation
• Contractures
 Factors which might impair wound
Repair
Systemic
• Age-very young and old
• Disorders of nutrition
• Vitamin C deficiency (collagen)
• Glucocorticoids
(immunosuppression +interfere
with formation of granulation
tissue and wound contraction)
• Diabetes/immunosuppression
(increase susceptibility to low
virulence organisms)
Local
• infection
• Poor blood supply
• Foreign bodies
• Type and volume of tissue injured
• Location of the injury - movement
 Bone
• Repair process same, slightly
modified
• Haemorrhage – hematoma –
facilities repair – ground for cells
to grow
• Removal of necrotic tissue
• Organisation of hematoma
• Special – capillaries accompanied
by fibroblasts and osteoblasts –
lay down irregular woven bone
(callus)
- replaced by lamellar bone
-gradually remodelled according
to direction of mechanical stress.
 Liver
• Hepatocytes -
excellent regenerative
capacity

• Hepatic architecture – poor

reconstruction if
excessively
damaged eg. Cirrhosis

• Combination
- Parenchymal
regeneration
- Scar formation
• Outcome depends
- Insult
- Location
- Extent
- Chronicity
 Kidney

• Epithelium regenerates
• Architecture – cannot
regenerate
- tubular damage – can
regenerate
- glomerular damage –
permanent – loss of
filtration capacity
- interstitial damage -
fibrosis
 Muscle

• Cardiac and smooth muscle –

permanent population- replaced by
scar tissue

• Voluntary (skeletal) muscle – limited

capacity for regeneration from satellite
cells, depends if muscle sheath intact
 Neural tissue

• Neurons - permanent cells – central nervous system

does not repair effectively
• NO FIBROBLAST proliferation in brain damage
• Necrotic tissue – liquefactive necrosis
• Glial cells - may proliferate in response to injury to
produce a glial scar or gliosis.

• Peripheral nerve damage - shows degeneration distal to

trauma and recovery depends on alignment and
continuity