Chapter 3: Tissue Repair Flashcards
Repair of damaged tissues occurs by two processes, what are these processes?
regeneration (restores normal cells) and scarring (the deposition of connective tissue)
When does repair occur by laying down a connective (fibrous) tissue?
If the injured tissues are incapable of regeneration or if the supporting structures of the tissue are too severely damaged to support regeneration
the regeneration of injured cells and tissues involves cell proliferation, which is driven by what?
growth factors and is critically dependent on the integrity of the ECM and by the development of mature cells from tissue stem cells
During tissue repair, several cell type proliferate- what are these different cell types?
the remnants of the injured tissue, vascular endothelial tissue, and fibroblasts
the ability of tissues to repair themselves is determined by what?
their intrinsic proliferative capacity and the presence of tissue stem cells
Based on intrinsic proliferative capacity and the presence of tissue stem cells, the tissues of the body can be divided into three groups. What are these groups?
Labile (continuously dividing) tissues, Stable tissues, and permanent tissues
Examples of labile cells?
hematopoietic cells in the bone marrow, stratified squamous epithelia of the skin, oral cavity, vagina, cervix, cuboidal epithelia of the ducts draining exocrine glands, columnar epithelia of the GI tract, uterus, and fallopian tubes, and the transitional epithelium of the bladder
Cells in stable tissues are said to be in what stage of the cell cycle?
they are quiescent- so they are in the G0 stage of the cell cycle
What are examples of stable cells/tissues?
the parenchyma of most solid tissues, such as liver, kidney, and pancreas; also include endothelial cells, fibroblasts, and smooth muscle cells
What are permanent tisses/cells?
they are considered to be terminally differentiated and non-proliferative in postnatal life.
What are 2 examples of permanent tissues/cells?
the majority of neurons and cardiac muscle cells
What can be said about injury to the brain or heart?
it is irreversible and results in a scar because neurons and cardiac myocytes cannot regenerate
What are growth factors typically produced and by what are they produced by?
growth factors are typically produced by cells near the site of damage; the most important source of growth factors is macrophages that are activated by tissue injury
Regeneration of the liver occurs by two major mechanisms. What are these mechanisms?
1) proliferation of remaining hepatocytes 2) repopulation from progenitor cells
In humans, resection of up to 90% of the liver can be corrected by what mechanism?
proliferation of the residual hepatocytes
What is the first stage of proliferation of residual hepatocytes?
priming phase: cytokines such as IL-6 (produced mainly by Kupffer cells) act on hepatocytes to make the parenchymal cells competent to receive and respond to growth factor signals
what is the second stage of proliferation of residual hepatocytes?
growth factor phase: growth factors such as hepatocyte growth factor (HGF) and TGF-alpha act on the primed hepatocytes to stimulate cell metabolism and entry of the cells into the cell cycle
The wave of hepatocyte proliferation is followed by what?
replication of nonparenchymal cells (Kupffer cells, endothelial cells, and stellate cells)
What occurs in the final stage of proliferation of residual hepatocytes?
termination phase: hepatocytes return to quiescence
In situations where the proliferative capacity of hepatocytes is impaired, how does regeneration of the liver occur?
such as after chronic liver injury or inflammation, the progenitor cells in the liver contribute to repopulation
where do the progenitor cells of the liver reside?
in specialized niches called canals of Hering
Restoration of normal tissue structure can occur only if what?
the residual tissue is structurally intact
Extensive destruction of the liver with collapse of the reticulin framework, as occurs in a liver abscess, leads to what?
scar formation- even though the remaining liver cells have the capacity to regenerate
repair by connective tissue deposition consists of sequential processes that follow tissue injury and inflammation. What is the next stage after inflammation?
cell proliferation: several cell types including epithelial cells, endothelial cells, and fibroblasts proliferate and migrate to close the now clean wound
why do endothelial cells proliferate?
to form new blood vessels
why do fibroblasts proliferate?
to lay down collagen fibers that form the scar
during repair by connective tissue deposition, what occurs after cell proliferation?
formation of granulation tissue
what is granulation tissue?
migration and proliferation of fibroblasts and deposition of loose connective tissue form granulation tissue
what is granulation tissue progressively replaced by?
deposition of collagen
How do macrophages play a central role in repair?
by clearing offending agents and dead tissue, providing growth factors for the proliferation of various cells, and secreting cytokines that stimulate fibroblast proliferation and connective tissue synthesis and deposition
what types of macrophages are primarily involved in the process of repair?
the alternatively activated (M2) macrophages
What is angiogenesis critical for?
in healing at sites of injury, in the development of collateral circulations at sites of ischemia, and in allowing tumors to increase in size
What is the first step in the process of angiogenesis? describe
Vasodilation: in response to nitric oxide and increased permeability induced by vascular endothelial growth factor (VEGF)
What is the role of VEGF in the process of angiogenesis?
promotes vasodilation by stimulating the production of NO and contributes to the formation of the vascular lumen
what is the role of fibroblast growth factors (FGFs)?
they stimulate the proliferation of endothelial cells
What enzymes in the ECM, degrade the ECM to permit remodeling and extension of the vascular tube?
matrix metalloproteinases (MMPs)
the laying down of connective tissue occurs in two steps: what are these steps?
migration and proliferation of fibroblasts into the site of injury and deposition of ECM proteins produced by these cells
what are the processes of laying down of connective tissue orchestrated by?
by locally produced cytokines and growth factors such as PDGF, FGF-2, and TGF-beta
What secretes the cytokines needed for the processes of laying down connective tissue?
mainly, alternatively activated (M2) macrophages, but also mast cells and lymphocytes if present
What is the most important cytokine for the synthesis and deposition of connective tissue proteins?
TGF-beta
the outcome of the repair process is influenced by a balance between what?
synthesis and degradation of ECM proteins
the degradation of collagens and ECM components is accomplished through what enzyme?
matrix metalloproteinases
What are the functions of TGF-beta?
it stimulates fibroblast migration and proliferation, increased synthesis of collagen and fibronectin, and decreased degradation of ECM due to the inhibition of MMPs
activated collagenases (MMPs) can be rapidly inhibited by what?
specific tissue inhibitors of metalloproteinases (TIMPs)
What is one of the most important systemic causes of abnormal wound healing?
diabetes
Nutritional status has profound effects on wound repair; what deficiencies specifically inhibit wound repair?
protein and vitamin C deficiencies
how do glucocorticoids affect wound healing?
their administrations may result in weakness of the scar due to inhibition of TGF-beta production and diminished fibrosis
what are some diseases that could cause poor perfusion and therefore inhibit wound healing?
peripheral vascular disease, arteriosclerosis, and diabetes or due to varicose veins
Inflammation arising where will result in the development of extensive exudates?
in tissues spaces such as pleural, peritoneal, or synovial cavities
Based on the nature and size of the wound, the healing of skin wounds is said to occur how?
by first or second intention
when does first intention wound healing occur?
when the injury involves only the epithelial layer
during first intention, what is seen within 24 hours at the site of the clot?
neutrophils
what happens within 24-48 hours of first intention wound healing?
epithelial cells from both edges have begun to migrate and proliferate along the dermis (closing the wound thinly)
When are neutrophils replaced by another cell type? and what is this other cell type?
By day 3 of first intention wound healing, neutrophils are replaced by macrophages and tissue granulation slowly invades the space
when does neovasvularization reach its peak during first intention wound healing?
by day 5
During first intention wound healing, by when is the scar compromised by a cellular connective tissue largely devoid of inflammatory cells and covered by an essentially normal epidermis?
by the end of the first month
What happens during a wound healing by second intention?
at first a provisional matrix containing fibrin, plasma fibronectin, and type III collagen is formed, but in about 2 weeks this is replaced by a matrix composed primarily of type I collagen
During wound healing by second intention, what helps close the wound?
wound contraction, which involves the formation of a network of myofibroblasts, which have contractile properties
What are 4 examples of chronic wounds?
venous leg ulcers, arterial ulcers, diabetic ulcers, and pressure sores
venous leg ulcers develop most often in what population of people?
the elderly as a result of chronic venous hypertension
Who is at risk for getting arterial ulcers?
individuals with atherosclerosis of peripheral arteries, especially associated with diabetes
when a surgical incision reopens internally or externally, what is this called?
wound dehiscence
what are the risk factors for wound dehiscence?
obesity, malnutrition, infections, and vascular insufficiency
What can excessive formation of the components of the repair process give rise to?
hypertrophic scars and keloids
If the scar tissue grows beyond the boundaries of the original wound and does not regress, what is it?
a keloid
who is more susceptible for developing a keloid?
african americans
when do hypertrophic scars generally develop?
after a thermal or traumatic injury that involves the deep layers of the dermis
contraction in the size of the wound is an important part of the normal healing process; what happens if this process is exaggerated?
the patient will have a contracture- most common areas are the palms, soles, and anterior aspect of the thorax
