TISSUE REPAIR

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TISSUE REPAIR
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Repair is the replacement of dead or damaged
tissues by new healthy tissues.
Resolution is the best type of repair. It entails
removal of tissue debris and inflammatory cells,
drainage of fluid, and probably mild
proliferation of the intact parenchymal cells
(e.g., healing of lobar pneumonia).
Regeneration is repair by the same type of cells
as those destroyed (e.g., repair by proliferation
of hepatocytes after liver cell injury).
Organization is repair by fibrous tissue (e.g.,
scarring).
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lobar pneumonia
Resolution
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Labile Cells-These are continually dividing
(regenerating) to replace cells that are dying
throughout life,they are derived from stem cells,
which possess a high capacity to
divide. Hematopoietic cells. Surface epithelia.
Epithelium of skin, oral cavity, cervix, vagina,
endometrium, respiratory passages,
gastrointestinal tract, and urinary tract.
TYPES OF CELLS
Labile Cells Stable Cells Permanent Cells
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Stable Cells-These are quiescent cells that do
not show active proliferation but that can divide
actively when stimulated. Parenchymal visceral
and glandular cells (e.g., liver, kidney,
pancreas, and parotid). Mesenchymal cells
Fibroblasts, endothelial cells, smooth muscle
cells, osteoblasts, and chondroblasts.
TYPES OF CELLS
Labile Cells Stable Cells Permanent Cells
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Permanent Cells-These are nondividing cells that
are unable to reproduce because they cannot
undergo mitosis Mature neurons When destroyed,
they are replaced by CNS connective tissue (i.e.,
glial cells) and fibers (e.g., brain infarct
healing by gliosis). Muscle cells have some
regenerative capacity,Cardiac muscles cannot
divide. Injury to them heals by fibrosis.
TYPES OF CELLS
Labile Cells Stable Cells Permanent Cells
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The reticulin stromal framework and basal lamina
are important in guiding the regenerating cells
to reconstruct the same histologic
architecture. If the insult is severe enough to
destroy the stromal framework and basal lamina,
the regenerating cells grow in a haphazard
fashion and the normal histologic architecture is
not maintained (e.g., cirrhosis).
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CELL CYCLE AND MOLECULAR BASIS OF GROWTH
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The cycling cell passes through the different
phases of the cell cycle G0 phase -resting or
quiescent phase G1 phase -the presynthetic
phase S phase -the DNA synthetic phase G2
phase -the premitotic phase and mitosis.
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The different types of cells in the body are at
different stages in the cell cycle.
The labile cells are continuously dividing and
continue in the cycle from one mitosis to the
next. The stable cells are the quiescent Go
cells that are not active but that can be
recruited into the cycle by certain stimuli. The
permanent cells leave the cycle and will never
divide again.
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Growth factors are chemical substances, usually
polypeptides, that are secreted by cells present
in the serum. They stimulate cellular growth.
Epidermal growth factor (EGF) is present in
secretions and fluids (e.g., saliva). is
mitogenic for many epithelial cells and
fibroblasts.
Platelet-derived growth factor (PDGF) is present
in platelet alpha granules, macrophages,
endothelial cells, smooth muscle cells, and some
tumor cells. It induces proliferation as well as
migration of monocytes, flbroblasts, and smooth
muscle cells.
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Thansforming growth factors (TGFs) Alpha
Beta is produced by many cells (e.g., T cells,
macrophages, platelets, and endothelial
cells). It is a growth factor for many epithelial
cells. It helps repair by stimulating fibroblast
chemotaxis and production of collagen and
fibronectin. It also inhibits collagen breakdown
by inhibiting proteases.
Fibroblast growth factors (FGFs) Acidic FGF,
which is confined to neural tissues Basic FGF,
which is present in many organs. Basic FGF is an
angiogenesis-promoting factor.
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Cytokines Macrophage derived growth factors
(IL-1, TNF, and integrins) can promote the
proliferation of fibroblasts).
Colony-stimulating factors (CSFs) granulocyte CSF
macrophage CSF Granulocyte-macrophage CSF
These stimulate bone marrow formation,
especially in leukemia and bone marrow
transplantation regimens.
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Ligand-Receptor Binding and Activation
The growth factor (ligand) unites with
its specific receptor located on the cell surface
(or intra-cellularly, as in steroid receptors)
and creates a ligand-receptor complex. The
latter stimulates tyrosine kinase, which in turn
activates the protein phosphorylation cascade,
ultimately moving the quiescent cell into the
growth cycle.
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the major types of cell surface receptors and the
principal signal transduction pathways
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COLLAGENS
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Collagens are composed of a triple helix of three
polypeptide alpha chains (tropocollagen molecule).
Different alpha chains create more than 15 types
of collagen.They are formed by fibroblasts. The
three alpha chains are held together by
hydroxyproline, which creates procollagen.
(Proline hydroxylation needs vitamin
C Procollagen is then released outside the
fibroblast. Cleavage of propeptides creates the
collagen fibrils. Extracellular lysyl
hydroxylysyl oxidation leads to crosslinking of
alpha chains and renders the collagen molecule
structurally stable.
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ADHESIVE GLYCOPROTEINS These are a group of
glycoproteins that link components of the
extracellular matrix together and to the cells
Fibronectin-a large glycoprotein formed by
fibroblasts and endothelial cells It is involved
in the attachment and migration of cells (e.g.,
inflammatory cells) and probably in cellular
growth and is present along cell surfaces and
basement membranes.
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ADHESIVE GLYCOPROTEINS
Integrins-transmembrane glycoproteins with
extracellular and intracellular domains. The
intracellular domain adheres to cytoskeletal
elements This signals attachment and locomotion.
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Laminin-is the most common adhesive glycoprotein
in the basement membranes. It binds extracellular
matrix components (e.g., collagen) to specific
cell surface receptors and assists in capillary
tube formation in angiogenesis.
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Chondronectin-binds the chondrocytes to type II
collagen in the cartilage matrix.
Osteonectin-binds the hydroxyapatite and calcium
ions to type I collagen in the bone matrix and
can initiate osteoid mineralization.
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ORGANIZATION-healing by granulation tissue that
matures into fibrous tissue
Granulation Tissue-is the red, granular soft
tissue that covers wound surfaces. It bleeds
easily and is highly resistant to infection. It
is made up of newly formed capillaries,
fibroblasts, and collagen bundles.
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Granulation tissue showing numerous blood
vessels, edema, and a loose ECM containing
occasional inflammatory cells. This is a
trichrome stain that stains collagen blue
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Angiogenesis (Neovascularization)
It is the process by which new capillaries are
formed. It starts by degradation of the basement
membrane of the parent vessel followed by
migration of endothelial cells.
Proliferation and maturation of endothelial cells
finally create newly formed capillary tubes.
Factors inducing angiogenesis include fibroblast
growth factor (FGF) and vascular endothelial
growth factor (VEGF).
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Angiogenesis (Neovascularization)
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HEALING OF WOUNDS
First (primary) intention involves healing of a
clean incised surgical wound
Second (Secondary) Intention Occurs in unclean,
infected, or traumatic wounds It differs from
healing by first intention quantitatively but not
qualitatively (i.e., the same process occurs but
with excessive scarring). An ugly scar is the
result.
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HEALING OF WOUNDS
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COMPLICATIONS OF REPAIR AND WOUND HEALING
Infection leads to healing by second intention.
Ulcer is defined as loss of surface epithelium
Sinus is a tract opened at one end and closed at
the other (e.g., pilonidal sinus, osteomyelitis
sinus).
Fistula is a tract opened at both ends
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Keloid is formed by excessive collagen
deposition, creating an irregular raised mass. It
is more common in nonwhites.
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Exuberant granulation is excessive granulation
tissue formation, creating a protruding red
fleshy mass
Fibromatosis is the aggressive proliferation of
fibrous tissue with characteristic local invasion
(e.g., desmoid tumors).
Traumatic neuroma is a painful nodule created by
Schwann cell hyperplasia and nerve fiber growth
after nerve injury or amputation
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FACTORS AFFECTING REPAIR
Nutrition Vitamin C and protein deficiency
inhibit collagen synthesis. Drugs
Corticosteroids affect collagen
formation. Infection This delays
healing Mechanical factors Foreign bodies
Talcum powder or suture material may create a
noninfective granuloma and delay healing.
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