Repair and healing

Dr. Mehzabin Ahmed

Outcomes of inflammation
Tissue repair

 Two separate processes underlie the repair of tissue damage

( caused by surgical resection, wounds, chronic inflammation
etc.):
 1.Regeneration – (replacement of injured cells by cells of
same type) results in restitution of lost tissues, requires an
intact connective tissue scaffold.
 2.Healing- may restore original structures but involves scar
formation; occurs when the extracellular matrix (ECM) frame
work is damaged; as well as in permanent tissues following
tissue necrosis.
Tissue proliferative activity

Tissues of the body are divided into 3 groups based on their proliferative
capacity
 Labile tissues ("continuously dividing tissues") are constantly
replenishing their neighbors which have died or been shed. Examples
include the epithelium of skin, mucous membranes, oviducts, ducts;
urothelium; endometrium; seminiferous tubules; bone marrow; in most
of these tissues , mature cells are derived from stem cells.
 Epidermis can regenerate from the skin adnexal structures (hair
follicles, sebaceous glands, sweat glands), enabling full removal of
epidermis as for a skin graft.
Tissue proliferative activity (contd.)

 Quiescent or Stable tissues ("discontinuous replicators") can

proliferate rapidly in response to need, especially when required
to replace lost neighbors. These include all glandular
parenchymal cells, endothelial cells as well as mesenchymal cells
such as fibroblasts,smooth muscle cells,chondrocytes, and
osteoblasts.
 The best example of regenerative capacity of stable cells is
the regeneration of liver after partial hepatectomy.
Tissue proliferative activity (contd.)

 Non dividing (permanent) tissues contain cells that have left the
cell cycle cannot undergo mitosis or be replenished after birth.
These cells include neurons, cardiac and skeletal muscle cells.

 Obviously, cells will not regenerate if there is inadequate blood

supply, inadequate nutrition, or complete destruction of their
connective tissue framework.
Cell populations and cell cycle phases
 Tissue response to injury: repair after injury can occur by regeneration which
restores normal tissue or by healing which leads to scar formation

Normal homeostasis
Balance of proliferation and apoptosis

injury
Regeneration Healing
Permanent tissues

Stable tissues
Renewing tissues
inflammation

fibrosis

Epidermis, Compensatory growth of Wound healing

GIT, Liver and kidney Scar formation
Hemopoeitic
Resolution

 Occurs when there has been minimal damage to tissue

architecture and the cells can regenerate.
 E.g.:Lobar pneumonia, under favourable conditions, the
injured area returns to its normal structure and function
 The inflammatory exudate is removed by liquefaction
and phagocytosis, damaged cells regenerate and
repopulate the injured alveoli
Healing by collagenous scar

 Organization is the process by which inflammatory exudate

is replaced by granulation tissue

 The process by which granulation tissue is subsequently

replaced by fibrous scar is called fibrous repair

Healing by collagenous scar (contd.)

 1.Organization and repair following acute inflammation;

e.g. severe structural damage to the supporting stroma as in
an abscess, fibrinous exudates on serosal surfaces, necrosis
in tissues containing permanent cells and
 2.Chronic inflammation eventually heals by scarring
 3. Healing of wounds (Tissue wounds including surgical
wounds)
inflammatory processes in body cavities may result in the
formation of adhesions, which are thin bands of collagenous
connective tissue, as seen here between the right lung and the
chest wall at autopsy. Adhesions, if extensive can restrict motion
or cause retraction to an abnormal position of internal organs.
 The best possible outcome following an inflammatory process is complete
resolution, leaving the tissues intact and undamaged. However, chronic
inflammation may occur in conjunction with some degree of scarring. Here,
chronic inflammation of the bronchi has led to dilation and scarring with
increased tan to white collagenous tissue.
Sequence of changes in healing

 Replacement of area of tissue damage by vascular

granulation tissue
 Progressive growth of fibroblasts in the granulation tissue
( fibrovascular granulation tissue)
 Progressive collagen synthesis and deposition in the
granulation tissue( fibrous granulation tissue),contraction of
area through the effects of myofibroblasts
 Production of dense collagen – collagenous scar
Healing of Tissue wounds
(including surgical wounds)
 Achieved by organization, repair and scar formation
 Healing by Primary intention : healing of closely apposed
surfaces as in a clean sutured surgical wound
 Healing by secondary intention: healing of open wounds
 Differences between the two relate to the amount of
granulation tissue required to fill the tissue defect
 Wound contraction – the process by which the surface
area of an open wound is reduced to about 10% of its
original size; characteristic of healing by secondary
intention , caused by contraction of myofibroblasts.
HEALING BY SECOND INTENTION
WOUNDS WITH SEPARATED EDGES)
Steps in wound healing by first intention (left)
and second intention (right).
Secondary healing differs from
primary healing in several
respects:

 inflammatory reaction is
more intense.
 Much larger amounts of
granulation tissue are
formed.
 wound contraction, by myo-
fibroblasts at the wound site
decreases the gap between
the dermal edges of the
wound.
 Substantial scar formation
and thinning of the
epidermis.
Stages in the healing of a sutured skin wound

 Day 1 : acute inflammatory response at the margins of

incision , epithelial cell regeneration begins

 Day 2: thin surface layer establishes epithelial continuity,

Macrophages begin to appear

 Day 3: granulation tissue begins to invade tissue space,

thickening of epithelial layer
 Day 5: vascular granulation tissue fills the incisional space,
swelling and redness subsides
 Day 7: sutures commonly removed , wound has about 10%
of tensile strength of the normal skin
 Day 10: fibrous granulation tissue,adds to wound strength
 Day 15: collagen deposition along the line of stress,pale
pink in appearance
 Day 30: 50% tensile strength
 3 months: max. tensile strength of 80%, scar
This is a healing biopsy site
on the skin seen a week
following the excision, The
skin surface has re-
epithelialized, and below this
is granulation tissue with
small capillaries and
fibroblasts forming collagen.
After a month, just a small
collagenous scar will remain.
Cellular events in wound healing

 5 key events in healing by organization and repair:

 Local vessels:
 1.angiogenesis

 Local support cells

 2.Divide to form fibroblasts and myofibroblasts
(mitogenesis)
 3.migratetowards the area of tissue damage
(chemotaxis and motility )
 4.secrete collagen (fibrogenesis)
 5. Produce collagen degrading enzymes ( remodeling)
Local and systemic factors influence healing

 Systemic factors:
 Inadequate nutrition ( protein, vit.C and Zinc)
 Steroids
 Diabetes Mellitus
 Local:
 Infection
 Foreign material
 Ischemia to tissues, radiation , denervation
This patient had diabetes mellitus for many years. This disease leads to
marked atherosclerosis with arterial narrowing. When peripheral arteries
to the legs are involved, then ischemia of soft tissues and bone occurs.
Even minor trauma leads to ulceration that heals poorly and often
becomes secondarily infected. A transmetatarsal amputation has already
been performed in this patient because of the severity of peripheral
vascular disease.
 Healing is promoted by:
 Removal of dead tissue to allow apposition of healthy tissues
 Administration of appropriate antibiotics in cases of infection
Healing in specialized tissues

 Damaged brain heals by growth of astrocytes and not by

fibroblasts; necrotic tissue is removed and replaced by
fluid,forming a cystic lesion,surrounded by glial tissue
 Repair of bone damage (fracture) : a fibrous scar is an inadequate
end-result in bone healing;
 in addition to granulation tissue formation and fibrous repair,
there is formation of a callus( mass of fibrous tissue,bone and
cartilage, from which healed bone will arise),
 with remodeling of callus the normal structure of bone prior
to fracture is re-established.
Myocardium: Healing by scar formation

There has been a previous extensive

transmural myocardial infarction involving
the free wall of the left ventricle.
Note that the thickness of the myocardial
wall is normal superiorly, but inferiorly is
only a thin fibrous wall. The infarction was
so extensive that, after healing, the
ventricular wall was replaced by a thin
band of collagen, forming an aneurysm.
Such an aneurysm represents non-
contractile tissue that reduces stroke
volume and strains the remaining
myocardium. The stasis of blood in the
aneurysm predisposes to mural thrombosis.
COMPLICATIONS IN CUTANEOUS WOUND HEALING

• excessive formation of the keloid

repair components
 hypertrophic scar;
 called a keloid

keloid

keloid
COMPLICATIONS IN CUTANEOUS
WOUND HEALING

• excessive formation of
the repair components
 exuberant
granulation (proud
flesh)
 pyogenic granuloma

 Raised red, soft,

gingival lesions
made up of
excessive
granulation tissue
called.
COMPLICATIONS IN CUTANEOUS WOUND
HEALING

1. Deficient scar formation leads to poor

scar formation and gaping of wounds
as in
• Wound dehiscence and
• Nonhealing ulcers

Infected Post Operative Wound Wound dehiscence

Case. This gentleman sustained burns from which he recovered, but is bothered by
tight scars. He has limitation of motion from burn scar and webbing on his hand and
his wrist......

• formation of contractures.

 
•

•
Excessive contraction in the size of
a wound cause contractures
are commonly seen after serious
burns and can cause restriction in
the movement of joints
Overview of Repair Responses
After Injury and Inflammation