Healing Repair

Dr.
Thuaibah bt Hashim
Learning objectives
• Define the healing process. Describe types of healing & the
prerequisite for each.
• List the types of tissue with regard to their regenerative
capacity giving examples of each.
• Describe the types of wound & the stages of healing, as well as
the cellular events & related peptide growth factors.
• Discuss the factors affecting healing.
• Describe the complications of healing.
• Discuss on healing process in special tissues such as bones and
nerves.
• Suggest some clinical applications of what you have learnt.
Definition
• Healing is a response to tissue injury,
and represent an attempt by the
organism to restore integrity to an
injured tissue.
• It overlaps the inflammatory process,
and it is only for didactic purposes that
the two are discussed separately.
Overview of tissue responses to injury
Tissue damage: cells die
Acute inflammation
Cells can Cells cannot Damaging agent

re-grow re-grow persists
Chronic
regeneration healing by repair inflammation
Restoration of Scar formation: Damaging agent

normal loss of overcome?
structure & fn specialized fn yes no
Types of body tissue &
regenerative capacity
1. Labile cells (continuously dividing cells)
follow cell cycle.
eg. epidermis, GIT surface epit., bone marrow
2. Stable cells (quiescent)
normally demonstrate low level of replication,
however can undergo rapid division in response to
stimuli eg. Liver, kidney, pancreas (parenchymal
cells of virtually all glandular organs of the body)
mesenchyme eg. Fibrous tiss and smooth muscle
vascular endothelial cells
3. Permanent cells (nondividing)
eg. Nerve cells, skeletal muscle, cardiac muscle
2 distinct repair processes
1. Restitution = Regeneration
replacement of injured cells by cells of same type,
sometimes leaving no residual trace of previous
injury
2. Fibrous repair = fibroplasia
replacement by connective tissue which leaves a
permanent scar
Similar mechanisms i) cell migration

ii) proliferation
iii) differentiation
iv) cell matrix interactions
RESOLUTION
2 prerequisites:
• Minimal damage to tissue architecture
• Cells can regrow e.g. Pneumonia
Death of epit cells
Bacte & toxins
(support stroma
remains intact)
Acute inflammatory exudate
Fluids, salt, fibrin, other proteins, neutrophils, macrophages
Resolution
Neutrophil enzyme render the exudate highly liquid (coughed up or
reabsorbed into blood/lymphatics)
Macrophages phagocytosed residual undigested debris – pass into
lymphatics to lymph nodes.
Remnant epit divide to reline alveolar spaces differentiating into
new Type I & II cells.
RESOLUTION
Acute Tubular Necrosis
Framework is intact
allowing regeneration of
tubular cells.
Diffuse Cortical Necrosis

Unable to regenerate, will
be replaced by scar tissue.
Fibrous repair
Vascular granulation tissue
Fibrovascular granulation tissue
Fibrous granulation tissue

Contractile effects of myofibroblast
Collagenous scar
Fibrous repair - scar
Stages of healing - surgical wound
• Day 1 neutrophils appear at margins of incision,
acute inflammatory response, epithelial cells at
wound edge undergo mitosis & begin to migrate
across wound
• Day 2 macrophages begin to infiltrate the incisional
space to demolish fibrin. Surface epit continuity is
reestablished in the form of a thin surface layer
• Day 3 Granulation tissue begins to invade tissue
space. Surface epit continuity is reinforced by
thickening of epit layer.
• Day 5 incisional space is filled with vascular
granulation tissue: collagen is progressively
deposited. Surface epit achieves normal thickness.
Acute inflammatory response at wound margins
begin to subside.
• Day 7 sutures commonly removed from skin
wounds. Wound has approx. 10% of tensile strength
of normal skin
• Day 10 Further fibroblast proliferation and collagen
deposition occur in granulation tissue adding more
strength
• Day 15 collagen deposition follows the lines
of tissue stress. Granulation tissue loses some
of its vascularity
• Day 30 wound now has 50% of tensile
strength
• 3 months wound achieves maximal 80% of
tensile strength of normal skin. It now
appears only marginally more vascular than
adjacent skin. Complete blanching of scar
takes several more months
Healing of skin wounds
• Healing by primary intention
– Closely apposed surfaces
• Healing by secondary intention
– Open wounds
Difference: amount of fill-in required to

bridge the tissue defect rather than any
special mechanistic differences.
INJURIES OF MEDICO-LEGAL IMPORTANCE
WOUND: (legal definition):' breach of the full thickness of the skin (or lining of
lip). This excludes abrasions, bruises, internal injuries and fractures!
WOUND: (medical definition)' disruption of the continuity of the tissues produced
by external mechanical force‘
INJURY: from the latin injuria (in- not, jus- the law). The term is often used
synonymously with wound but can have a wider use, including damage to tissues by
heat, cold, chemicals, electricity, radiation, in addition to mechanical force
LESION: from the latin laesio (a hurt). Originally meant injury, now more widely
applied to include '' any area of injury, disease or local degeneration in a tissue
causing a change in its function or structure'‘
TRAUMA - bodily harm with or without structural alterations resulting from

interaction with physicochemical agents, imparting energy to tissues.
May cause morphologically apparent damage (wound) or produce physiological
imbalance (eg reflex cardiac arrest by neural stimulation) and secondary effects (eg
thrombosis, infection, obstruction of tubular organs)
Types of wounds
• Abrasion
• Bruise = contusion
• Laceration
• Incised wound
– Slashed
– stab
Bruise : Blunt injury to the tissues which damage blood
vessels beneath the surface, allowing blood to
extravasate into surrounding tissues.
Abrasion : superficial injury to the skin /
tissue caused by rubbing or scraping
confined to epidermis
Laceration : splitting or tearing wound caused by
blunt injury which passes through the full thickness
of the skin
Incised wound : sharply cut injuries,
Slashed : the length is Stab : the depth is greater

greater than depth than length
Factors that influence wound healing
• Type, size & location of the wound
• Vascular supply diabetics heal poorly
• Infection delay healing, more granulation tissue &
scarring
• Movement wound over joints do not heal well due to
traction
• Overall nutrition
• Age younger is definitely better
Factors that influence wound healing
• Foreign material rationale for surgical debridement
of necrotic material from large wounds
• Hormones corticosteroids drastically impair healing

because of their profound effect on inflammatory cells.
Complications of wound healing
• Defective scar formation dehiscence or
ulceration is usually due to wound infection (common),
malnutrition (scurvy – rare) and hypoxia usually due to
inadequate vascularity in a skin flap (common)
• Extensive scar formation keloids are the
result of overexuberant production of scar tissue which is
primarily composed of Type III collagen. Thought to be due to
genetic factors, perhaps lack of proper collagenases to degrade
Type III collagen
• Contraction excessive contraction of a wound is known
as a contracture. They are a special problem in the treatment of
extensive burns.
Wound dehiscence
Keloid
Cellular events in wound healing
• Angiogenesis
• Mitogenesis
• Chemotaxis & motility
• Fibrogenesis
• Remodelling
Peptide growth factors
• Platelet derived growth factors (PDGF)
– Mitogenesis and chemotaxis
• Basic fibroblast growth factors
– Angiogenesis, mitogenesis and chemotaxis
• Transforming growth factors
• Interleukin-1 fibrogenesis
• Tumour necrosis factor
CONCLUSIONS
The magic behind the seemingly precise
orchestration of these events under normal
conditions remains beyond our grasps, but
almost certainly lies in the regulation of
specific soluble mediators and their receptors
on particular cells, cell-matrix interactions,
and a controlling effect of physical factors,
including forces generated by changes in cell
shape & plasticity. (Wang et.al.)
Clinical applications
•Factors that influence wound healing
–Toilet & suture
•Complications of wound healing

–eg. Prevent contracture or excessive scar
in burns
•Stages of healing
– Remove suture on Day 7
Clinical applications
• Peptide growth factors in chronic ulcers
– Becaplermin = Regranex®
recombinant PDGF as topical gel to
promote granulation tissue
– Only PDGF & VEGF approved by FDA
currently.
– Autologous plasma as eye drop
– Autologous platelet extract for diabetic
wound.
Recent advances in wound care
Newer occlusive dressings speed up re-
epithelialization, stimulate collagen synthesis,
create a hypoxic environment at the wound bed
to promote angiogenesis & decrease pH at
wound surface, creating an environment
inhospitable to bacterial growth, which
decreases the rate of wound infection.
They have an edge over gauze dressings in
terms of patient comfort, convenience and
compliance as well as better cosmetic results
because of reduced scarring.
Recent advances in topical
wound care
Sujata Sarabahi
Indian Journal of Plastic Surgery
2012 Volume : 45, Issue : 2
Page : 379-387
http://
www.ijps.org/viewimage.asp?im
g=ijps_2012_45_2_379_101321
_t3.jpg
Maggot
wound
debridement
The parable of those
who take protectors
other than God is that
of the spider, who builds
(to itself) a house;
But truly the flimsiest
of houses is the
spiders’s house; -
If they but knew.
Al Quran 29:41
Google ‘panacea define’
panacea
[ ˌpanəˈsiːə ]
NOUN
noun: panacea · plural noun: panaceas
a solution or remedy for all difficulties or
diseases:
"the panacea for all corporate ills"
synonyms: universal cure · cure-all

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Dr.

Cells can Cells cannot Damaging agent

Restoration of Scar formation: Damaging agent

Similar mechanisms i) cell migration

Diffuse Cortical Necrosis

Fibrovascular granulation tissue

Fibrous granulation tissue

Difference: amount of fill-in required to

TRAUMA - bodily harm with or without structural alterations resulting from

Slashed : the length is Stab : the depth is greater

• Hormones corticosteroids drastically impair healing

•Complications of wound healing

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