78
U N I T 1
Cell and Tissue Function
Healing by ConnectiveTissue
Repair
The primary objective of the healing process is to fill
the gap created by tissue destruction and to restore the
structural continuity of the injured part. Tissue regen-
eration refers to the restoration of injured tissue to its
normal structure and function by proliferation of adja-
cent surviving cells. As discussed earlier in the chapter,
cell renewal occurs continuously in labile tissues such as
gastrointestinal epithelium and skin. Regeneration can
also occur in parenchymal organs with stable cell popu-
lations but, with the exception of the liver, is usually a
limited process. It should be pointed out that extensive
regeneration can occur only if the residual tissue is struc-
turally and functionally intact. If the tissue is damaged
by infection or inflammation, regeneration is incomplete
and accomplished by replacement with scar tissue.
When regeneration cannot occur, healing by replace-
ment with a connective (fibrous) tissue occurs, a process
that terminates in
scar formation
. The term
fibrosis
is often
used to describe the extensive deposition of collagen that
occurs in organs that are incapable of regeneration.
2
When
this occurs, fibrous tissue grows into the area of damage,
converting it to a mass of fibrous tissue, a process called
organization
.
1,2
It can also occur in serous cavities (pleura,
peritoneum) when excessive exudate accumulates and can-
not be cleared. In the pericardium, fibroblasts secrete and
organize collagen within fibrous strands, thereby binding
the visceral and parietal pericardia together
1
(Fig. 4-4).
Fibrous strands sometimes become organized within the
peritoneal cavity following abdominal surgery or perito-
nitis. These strands of collagen, called
adhesions,
can trap
loops of bowel and cause obstruction.
1
Phases of Repair
Repair by connective tissue deposition can be divided into
three phases: (1) hemostasis, angiogenesis, and ingrowth
of granulation tissue; (2) emigration of fibroblasts and
deposition of extracellular matrix; and (3) matura-
tion and reorganization of the fibrous tissue (remodel-
ing).
1,2,10–16
It usually begins within 24 hours of injury
and is evidenced by the migration of fibroblasts and the
induction of fibroblast and endothelial cell proliferation.
2
By 3 to 5 days, a special type of tissue called
granulation
tissue
is apparent.
2
The granulation tissue then progres-
sively accumulates connective tissue, eventually resulting
in the formation of a scar, which is then remodeled.
Angiogenesis and Ingrowth of Granulation
Tissue
Granulation tissue is a glistening red, moist connective
tissue that fills the injured area while necrotic debris is
removed
1,2
(Fig. 4-5). It is composed of newly formed
capillaries, proliferating fibroblasts, and residual inflam-
matory cells. The development of granulation tissue
involves the growth of new capillaries (angiogenesis).
Angiogenesis is a tightly regulated process that includes
migration of endothelial cells to the site of tissue injury,
those that are unable to regenerate. Stem cells
are undifferentiated cells of continuously dividing
tissues that have the capacity to generate
multiple cell types.
■■
Tissue regeneration and repair are mediated
by growth factors that increase cell size, cell
division, and cell differentiation, and enhance
the production of specialized extracellular matrix
(ECM) proteins by cells such as fibroblasts. Among
its many functions, the ECM aids in the regulation
of cell proliferation, movement, and differentiation
during wound repair by providing a foundation for
cell adhesion and a reservoir for growth factors.
SUMMARY CONCEPTS
(continued)
FIGURE 4-4.
Organized strands of collagen (arrows) in
constrictive pericarditis. (From Sephal GC, Davidson JM.
Repair, regeneration, and fibrosis. In: Rubin R, Strayer DS, eds.
Rubin’s Pathology: Clinicopathologic Foundations of Medicine.
6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott
Williams &Wilkins; 2012:94.)
