GENERAL PATHOLOGY

2. TISSUE REPAIR
BY
DR. ABDUL AZIZ SHAIKH
M.B.B.S&M.PHIL ,FCPS-1 PATH

3. Overview
• Repair, sometimes called healing,
Restoration of tissue architecture and
function after an injury.
• Repair of damaged tissues occurs by
two types of reactions: regeneration by
proliferation of residual (uninjured)
cells and maturation of tissue stem cells,
and the deposition of connective tissue
to form a scar

4. • Regeneration. Some tissues are able to
replace the damaged components and
essentially return to a normal state; this
process is called regeneration.
• Regeneration occurs by proliferation of
cells that survive the injury and retain the
capacity to proliferate, for example, in the
• rapidly dividing epithelia of the skin and
intestines, and in some parenchymal
organs, notably the liver

5. Connective tissue deposition
(scar formation).
• If the injured tissues are incapable of
complete restitution, or if the
supporting structures of the tissue are
severely damaged, repair occurs by
the laying down of connective
(fibrous) tissue, a process that may
result in scar formation

6. • The term fibrosis is most often used to
describe the extensive deposition of
collagen that occurs in the lungs, liver,
kidney, and other organs as a
consequence of chronic inflammation,
• or in the myocardium after extensive
ischemic necrosis (infarction).

7. • If fibrosis develops in a tissue space
occupied by an inflammatory exudate, it is
• called organization
• Both processes involve the proliferation of
• various cells, and close interactions
between cells and the extracellular matrix
(ECM)

9. Cell and Tissue Regeneration
• The regeneration of injured cells
and tissues involves cell
proliferation, which is driven by
growth factors and is critically
dependent on the integrity of the
extracellulartrix, and by the
development of mature cells from
• stem cells.

11. TISSUE RESPONSE TO INJURYTISSUE RESPONSE TO INJURY
injury
regeneration healing
wound chronic inflammation
wound healing
scar formation fibrosis
stable tissues
compensatory
growth
renewing
tissues
epidermis
GI tract
hemopoetic

12. Cell Proliferation: Signals and
Control Mechanisms
• Several cell types proliferate
during tissue repair. These include
the remnants of the injured tissue ,
vascular endothelial cells, and
fibroblasts (the source of the fibrous
tissue that forms the scar to fill
defects that cannot be corrected by
regeneration).

13. Based on intrinsic proliferative capacity.
Body cells are divided into three groups.
• Labile (continuously dividing) tissues.
Cells of these tissues are continuously
being lost and replaced by maturation from
tissue stem cells and by proliferation
• of mature cells.
• Hematopoietic cells and the majority of
surface epithelia,such as the stratified
squamous epithelia of the skin,oral cavity,
vagina, and cervix;

14. • the cuboidal epithelia of the ducts
pancreas, biliary tract); the columnar
epithelium of the gastrointestinal tract,
uterus, and fallopian tubes; and
• the transitional epithelium of the
urinary tract.
• Hematopoietic cells of bone marrow
• These tissues can readily regenerate
after injury as long as the pool of
stem cells is preserved.

15. QUIESCENT (STABLE) CELLS:
• These cells normally have a low level
of replication but are capable of
undergoing rapid division in response
to injury.
• E.g: parenchymal cells of liver, kidney
and pancreas.
• Mesenchymal cells : smooth muscles,
cartilage, connective tissue, fibroblast
and vascular endothelial cells.

16. NON DEVIDING (PERMANENT) CELLS:
• Contain those cells that have left cell
cycle and can not undergo mitotic
division in postnatal life.
• nerve cells (neurons)
• cardiac muscles.
• skeletal muscles.

17. • GROWTH FACTORS:
The most important chemical mediators
are polypeptide growth factors which are
circulating in the serum or produced locally
by the cells.
a: epidermal growth factors
b: PDGF
c: FGF
d: VEGF
e: cytokines e.g. IL1
• INHIBITORY FACTORS:
a: TGF beta
b: TNF

18. REPAIR BY CONNECTIVE TISSUE
• Condition in which tissue repair is
achieved by scar formation:
1. When resolution (recovery) fails to occur
in an acute inflammation.
2. When parenchymal cell necrosis can not
be repaired by regeneration because:
a. necrotic cells are permanent cells.
b. stable cells are destroyed.
c. necrosis is so extensive that no cells
are available for regeneration.

19. PHASES OF REPAIR BY SCAR
FORMATION
1. PREPARATION: the area of injury is prepared
for scar formation by removal of the inflammatory
exudate by the lymphatics.
2.INGROWTH OF GRANULATION TISSUE:
if resolution has not occurred , fibroblasts and
vascular endothelial cells begin proliferating to
form a specialized type of tissue that is hallmark
of healing, called granulation tissue. On gross
examination it is pink, soft and granular because
of numerous capillaries. On microscopic exam:
formation of new blood vessels and the
proliferation of fibroblasts.

20. Granulation tissue

22. 3. PRODUCTION OF FIBRONECTIN: it is a
glycoprotein that plays key role in the formation
of granulation tissue and is present in large
amount during wound healing. In early phases, it
is derived from the plasma, and latter
synthesized by fibroblasts, macrophages and
endothelial cells in granulation tissue.
4. COLLAGENIZATION (FIBROSIS): collagen is
the major fibrillary protein of connective tissue,
synthesized by fibroblasts and is responsible for
the tensile strength of scar tissue.

23. 5. MATURATION OF SCAR: when the scar
becomes mature , the amount of collagen
increases and the scar becomes less cellular
and less vascular and is white on gross
examination.
6. CONTRACTION AND STRENGTHENING: it is
final phase of scar formation. Contraction
decreases the size of scar and enable the
surviving cells of the organ to function with
maximum effectiveness.

25. REPAIR AND WOUND HEALING
• The body has ability to replace the injured
or dead cells and to repair tissues after
inflammation.
• When injurious agent damage the cells
and tissues, the body gives a response to
remove the injurious agent and damaged
tissue and preparing the surviving cells for
replication leading to repair.
• Healing means replacement of injured
tissue into viable tissue.

26. • Repair occur by two processes:
• REGENERATION: replacement of injured
tissue by parenchymal cells of the same
type.
• FIBROPLASIA / REPAIR BY
CONNECTIVE TISSUE: replacement of
injured tissue by connective tissue i.e.
fibroplasia or fibrosis which leaves a
permanent scar.

27. PROLIFERATIVE POTENTIAL OF
DIFFERENT CELL TYPE
• The cells of the body are divided into three
groups on the basis of their regenerative
capacity:
1. CONTINOUSLY DEVIDING (LABILE) CELLS:
these cells proliferate throughout life,
replacing those cells that are continuously
dying.
e.g. a. stratified squamous epithelium of skin,
oral cavity, vagina and cervix.
b. cuboidal epithelium of the ducts draining
exocrine organs e.g. salivary glands, pancreas
and billary tract.

28. CONTROL OF CELL GROWTH
• cellular proliferation is largely regulated by
biochemical factors produced in the local
microenvironment that can either stimulate
or inhibit cell growth . The factors that
stimulate cell growth are called growth
factors while that inhibit growth are called
inhibitory factors.

29. Role of extracellular matrix
in wound healing and scar formation
• Extracellular matrix (ECM) is formed by
specific secreted macromolecules that
form a network on which cells grow and
migrate along
• ECM is secreted locally and forms a
significant proportion of the tissue volume

30. • Fibrous structural proteins
– Collagens
• Collagens are the most abundant proteins
• 27 different types
• Type I,II, III, V and XI are the most abundant
(interstitial or fibrillar collagens)
• Provide tensile strength of tissue
• Fibrillar collagen requires hydroxylation of
proline and lysine in procollagen which is
dependent on Vitamin C
• Type IV is the main component of Basemant
membrane and forms sheets)

31. Three groups of macromolecules constitute
the ECM
• Fibrous structural proteins
– Collagen
– Fibrillins
• Adhesive glycoproteins
– Cadherin
– Integrins
– Immunoglobulin family
– Selectins
• Proteoglycans and Hyaluronic Acid

32. • ECM sequesters
– water that provides turgor to soft tissues
– and minerals that provides rigidity to skeletal
muscles
– Forms a reservoir for growth factors
• ECM proteins assemble into two general
organizations
– Interstitial matrix (present between cells)
– Basement membrane [BM] (produced by
epithelial and mesenchymal cells and is
closely associated with the cell surface)