Chapter 2

By Luying Liu M.D.

Department of Pathology
Stimuli or stress can lead the cell
damage (degeneration and necrosis)
In the same time, injured cells
release some soluble factors to star
the process of repair
Repair: the process to restore the
destroyed cells and tissue by
regenerating the same cell type and
connective tissue
Tissue Repair

Regeneration
complete regeneration
Healing
incomplete regeneration
A complete restore or incomplete
restore of injured tissue depends on
 ability of regeneration of injured
parenchymal cells
 degree of injury (the original
framework remains or not)
 Cell Proliferation

Classification of cells by their

proliferative potential
 Labile (epithelium of skin, respiratory
tract, gastrointestinal tract and
urinary tract, lymphoid cell, et al)
 Stable (parenchymal cells in liver,
kidney, pancreas, salivary gland, et
al)
 Permanent (myocardium, skeletal
muscle, neuron)
 Labile cells

normally a continuous process of

active replacement is occurring. The
chances of restoration by regeneration
are excellent.
Examples: the covering epithelium,
the bone marrow cells and the
lymphoid cells.
 Stable cells

Although normally the replacement

requirements are minimal, they have not
lost the capacity to proliferate in
response to stimulation. Chances of
regeneration remain.
Examples: adenocytes of parenchymal
viscera (including endocrine); all stromal
elements.
 Permanent cells

Normally are unable to multiply after

the growth early in life.
Examples: nerve cells, striated and
cardiac muscle cells, skeletal muscle
cells.
 The Processes of
Regeneration of Various
Tissues

Epithelium
 covering epithelium
 glandular epithelium

fibrous tissue
blood vessel
neuron (axon, myelin sheath)
covering epithelium
Glandular epithelium
Fibrous tissue

fibrous cell
 Blood vessel

Angiogenesis
(Capillary regeneration)

by sprout form
Steps in the process of angiogenesis
proteolytic degradation of the parent
vessel BM, allowing formation of a
capillary sprout
migration of endothelial cells from the
original capillary toward an angiogenetic
stimulus
proliferation of the endothelial cells
behind the leading edge of migrating cells
maturation of endothelial cells with
inhibition of growth and organization into
capillary tubes
Big blood vessels:

Endothelial cells could be

perfect restoration by
complete regeneration; but
cutting smooth muscle are
connected by scar.
 Regeneration of
peripheral nerves
traumatic neuroma
Repair by connective tissue
 Repair by Connective
Tissue (Fibrosis)

Severe or persistent tissue injury

destroy
 parenchymal cells
 stromal framework

incomplete repair by unregenerated

parenchymal cells with fibrosis
The main components of connective
tissue repair are angiogenesis,
migration and proliferation of
fibroblasts, collagen synthesis, and
connective tissue remodeling.
Granulation tissue is the initial event in
the repair of an injury, and consists of
richly vascular connective tissue which
contains capillaries, young fibroblasts,
and a variable infiltrate of inflammatory
cells
Do not confuse with GRANULOMA
pink, soft, moist, and granular appearance
24
LM:

① fibroblasts:
② new capillaries: capillary sprout and migrate
toward the wound. The new capillary endothelial
cells are swollen and capillary tubes are narrow.
These new vessels have leaky interendotheial
junctions. Allow the passage of proteins and red
cells into the extravascular space, thus, new
granulation tissue is often edematous.
③ inflammatory cells
Granulation tissue can occur in 2 to 3
days after tissue injury, from the bottom
up or growth toward the center from the
periphery, and then fill the wound.
After 1 to 2 weeks, the
growth of granulation
tissue is mature in
sequence. The water
out of cells gradually is
reduced by absorption.
Inflammatory cells
decreased and
gradually disappeared.
The capillaries number
reduced.
Granulation tissue then
progressively accumulates
connective tissue matrix,
eventually resulting in the
formation of a scar.

hyaline degeneration
occurs.
Roles of Granulation Tissue in
Fibrous Repair

Protect the wound and anti-infection

Connect the separated tissue, restore
the lost tissue and support them to keep
the integrity of body
Growth into the necrotic tissue,
hemorrhage, thrombi, inflammatory
exudate and replace them(organization)
 Scar Remodeling
A scar after surgical operation or
trauma will become softer, smaller
because of degradation of collagens
and other elements of ECM by
metalloproteinases (collagenases)
Over growth of scar is called keloid
Wound Healing
1. Definition:
Refers to the body’s replacement of
destroyed tissue by living tissue

2. Stages in healing of wound

(1) Escape of blood and exudates

(2) Acute inflammation
 (3) Contraction of the wound. The
causes of contraction are not known but
possible mechanisms are:

① Shrinkage of scab in superficial wounds

② Contraction properties of granulation
tissue attributable to contraction of
myofibroblasts or tissue re-modeling.
(4) Proliferation and migration of
fibroblasts and endothelial cells.

(5) Progressive increase in mature

collagen fibres during the second
week forming a scar.

(6) Loss vascularity and shrinkage of

the scar.
 Healing of Skin Wound

first intention: the usual case with a surgical

wound, in which there is a clean wound with
well-apposed edges, and minimal clot
formation
Second intention: when wound edges cannot
be apposed, (e.g., following wound infection),
then the wound slowly fills with granulation
tissue from the bottom up. A large scar
usually results.
Secondary healing differs from primary healing
in several respects:
A larger clot or scab forms at the surface of the
wound. Inflammation is more intense because large
tissue defects. It has a greater volume of necrotic
debris, exudate, and fibrin that must be removed.
Much larger amounts of granulation tissue are formed.
A greater volume of granulation tissue generally
results in a greater mass of scar tissue. Secondary
healing involves wound contraction.
Fracture healing
Bone regeneration ability is very strong. In
general, a good simple traumatic fractures can
be completely heal, recovery of normal
structure and function after a few months.
hematoma formation bony callus formation

Soft tissue callus formation

Bone remodeling
42
Factors that Influence Wound
Healing
Overall nutrition: vitamin and protein
deficiencies lead to poor wound healing,
especially vitamin C, which is involved
in collagen synthesis
Age: younger is definitely better!
Hormones - corticosteroids drastically
impair wound healing, because of their
profound effect on inflammatory cells
Factors that Influence Wound
Healing
Type, size, and location of the wound
Vascular supply (diabetics heal poorly)
Infection - delays wound healing and leads to
more granulation tissue and scarring
Movement - wounds over joints do not heal
well due to traction
Radiation - ionizing radiation is bad, UV is
good
310 Granulation tissue in
wound healing
Skin wound
necrosis
Granulation tissue
necrosis

Granulation tissue
 necrosis

Granulation tissue
inflammatory cells capillaries

fibroblast
Thank you for your
attention!