Tissue Injury and Repair Flashcards
The ____ ____ to infection and injury begins the process of repair.
Inflammatory response
Two main repair processes:
1. _____:restoration of normal cells
2. ____/____: deposition of connective tissue
Ultimate repair is usually a combination of both.
Regeneration
Scarring/fibrosis
Regeneration:
1. ____ of differentiated cells that survive injury
2. Tissue ____ ____ produce new differentiated cells
Proliferation
Stem cells
Regeneration is generally limited to some components of most tissue and requires ____ ____ ____.
Intact supporting structures
Scarring/fibrosis:
The injured area is ____ with connective (fibrous) tissue. Occurs when either cells of injured tissue are not capable of ____ or ____ ____ are too severely damaged.
Patched
Regeneration
Supporting structures
Scarring/fibrosis does not replace normal function of the tissue because the injured cells are replaced by ___ ___, which provides ____ but not function.
Connective
Structure
A tissue’s ability to repair depends on ____ capacity and ___ ___. There are three classes of tissue in this regard:
Proliferation
Stem cells
Labile tissue, stable tissue, permanent tissue
____ tissue is constantly dividing. ____ tissue is quiescent but not able to divid if needed. ____ tissue is not able to divid.
Labile
Stable
Permanent
Labile tissue is constantly turning over by stem cells and proliferation of mature cells.
Examples of Labile tissue and cells:
Lungs: type II pneumocytes, skin (basal cells), GI tract (Crypt cells), hematopoietic cells (CD34+ cells)
Picture of Labile tissue:
Stable tissue is made of ____ cells (G0). Capable of proliferating when tissue is injured or lost.
Examples:
Quiescent
Solid tissues such as liver, kidney, pancreas
Connective tissues such as endothelium, smooth muscle, and fibroblasts
Picture of stable tissue:
Permanent tissue cells are terminally differentiated and can’t ____. Repair is almost entirely ____.
Examples:
Proliferate
Fibrosis
Most neurons, cardiac and skeletal muscle.
Picture of permanent tissue repair:
Regeneration is driven by ___ ___ that are derived from activated ____ at the site of injury. Also derived from platelets, epithelial cells, Stromal cells, sequestered pool in extracellular matrix.
Growth factors
Macrophages
Regeneration depends on the integrity of the ____ ____. Some growth factors are present bound to the ___ ___ and therefore disruption of the ___ ___ could result in growth factor expression.
Extracellular matrix
Extracellular matrix
Extracellular matrix
Three phases of scarring/fibrosis:
1. _____: day 1 to 3. Cellular mediators involved are platelets, neutrophils, and macrophages. There is acute inflammatory response with macrophages clearing debris.
Inflammatory
Picture of inflammatory response:
Three phases of fibrosis:
2. _____: day 3 to weeks. Fibroblasts, myofibroblasts, endothelial cells, epithelial cells, and macrophages. They establish _____ ___, angiogenesis, epithelial cell proliferation, and type III collagen deposition
Proliferation
Granulation tissue
Picture of granulation tissue:
______ is stimulated by VEGF. It stimulates both migration and proliferation of endothelial cells. Promotes vasodilation by stimulating the production of ___ ___. Contributes to the formation of vascular lumen
Angiogenesis
Nitric oxide
Three phases of fibrosis:
3. _____: weeks to months. ____ are the cellular mediators. They replace type III collagen deposition with type I collagen. _____ contract to bring the wound edges together and add strength.
Remodeling
Fibroblasts
Macrophages
____ collagen provided a temporary structure in the injured area. ___ collagen is laid down in an orderly fashion facilitated by ____ and ___.
Type III
Type I
Fibroblasts
Macrophages
After it’s deposition, the connective tissue in the scar counties to be modified and remodeled by ____ _____.
Matrix metalloproteinases (MMP)
Diagram of tissue repair:
Regulation of regeneration and repair:
_____ M1 and M2 activation.
M1:
M2:
Macrophage
Clears offending agents and dead tissue
Provides growth factors causing proliferation of various cells
M2:
Macrophages secrete cytokines that stimulates _____ to proliferate and deposited connective tissue ECM.
Fibroblasts
M1 and M2 activation of macrophages is ___ ___. Macrophages are initially classically activated (M1), but are gradually replaced by alternatively activated type (M2).
Temporally regulated
___ is the most important cytokine in fibrosis. It is produced by most cells in granulation tissue including M2 macrophages.
TGF-beta
TGF-beta stimulates fibroblast ___ and ___. It increases synthesis of ___ and ___. It decreases degradation of ECM by inhibiting ___ ____. It also has anti-inflammatory properties
Migration
Proliferation
Collagen
Fibronectin
Matrix metalloproteinases (MMPs)
____ limits and terminates the inflammatory response.
TGF-beta
Table of growth factors:
Wound strength:
At week one, the wound is at about ____ strength of normal skin. Gradually, more ___ and less ___ ___ increases the strength
10%
Collagen
Granulation tissue
Wound strength:
After 2 moths, maximum strength is achieved, still only ___ of original tissue strength
75%
Complications of tissue repair:
___ ___: clinical factors can impede the repair process
___ ___: hypertrophic scars and keloid. Contractures
Chronic wounds
Excessive scarring
Delayed wound healing occurs in ____, causing prolonged inflammation and ongoing injury.
Infection
____ results in delayed wound healing due to poor perfusion and neuropathy leading to mechanical factors
Diabetes
___ ___ contributes to delayed wound healing. Vitamin C and protein deficiency both result in impaired ___ synthesis. Zinc deficiency inhibits replacement of ____ collagen to ___ collagen.
Nutritional deficiencies
Collagen
Type III
Type I
____/____: can contribute to delayed wound healing. They reduce inflammation but also inhibit fibrosis (this can be good or bad).
Medications/steroids
___ ___ can contribute to delayed wound healing. Healing wounds are weaker than native tissue and can be pulled apart
Mechanical stress
____: is poor perfusion that can contribute to delayed wound healing. Lack of nutrients needed for repair.
Ischemia
___ ___ can lead to delayed wound healing by serving as continued stimuli for chronic inflammation and ongoing injury
Foreign material
____ is rupture of a wound, most common after abdominal surgery
Dehiscence
____ ___ is excess production of scar tissue that is localized to the wound
Hypertrophic scar
____ is excess production of scar tissue that is out of proportion to the wound. Characterized by excess ____ collagen. It classically affects earlobes, face, and upper extremities.
Keloid
Type III
Pictures of hypertrophic scar:
It is limited to boundaries of original wound.
Picture of keloids:
Microscopy of keloid scarring:
Contains keloidal collagen that are disorganized
Scar ____ is an exaggeration of normal contraction of the wound during healing. Prone to developing in the palms, soles, and anterior aspect of the thorax
Contracture
____ ___: a sutured surgical incision with tightly apposed edges
___ ___: a wide open wound due to more inflammation and more granulation tissue
First intention
Second intention
____ ____ plays a major role in ultimate wound closure.
Myofibroblastic contraction
Cutaneous wound healing picture :
Macrophages largely replace neutrophils by day 3. Granulation tissue starts to develop.
Day 5: _____ aided by ___ and granulation tissue peaks. Fibroblasts begin to lay down type III collagen
Neovascularization
VEGF
Two weeks: type I collagen replaces Type III and greatly increases cellularity and blood vessels decrease
1 month: cellularity markedly diminished and scar contracts via action of ____.
Myofibroblasts
