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What is Wolff's Law?
tissue responds to the physical demands placed upon it, resulting in remodeling and realignment along lines of tensile force or stress
To strengthen a tissue, what must it be exposed to?
progressively increasing loads (ex: bone remodeling is influenced by the level and distribution of the functional strains generated within the bone)
Types of excessive stress?
A high-magnitude stress applied for a brief period (hit with a baseball bat)
A low-magnitude stress applied for a long duration (pressure ulcer formation)
A moderate-magnitude stress applied to the tissue many times (carpel tunnel syndrome)
If stress applied to a tissue is too great, what will happen?
the tissue will fail (plastic deformation), with rupturing and tearing - macrotrauma
What does tissue plastic deformation result in?
This results in a 3rd degree sprain (ligament) or strain (tendon)
What can frequent repetitions of stress (cyclic stress loading) lead to?
- tissue failure with lower levels of stress
- repeated microtrauma
- Results from accumulated damage (fatigue failure)
What occurs immediatly after tissue injury?
Inflammation - a critical part of tissue repair process
What is injured tissue less tolerant of?
Stress - injured and inflamed tissue must be protected from subsequent excessive stress
Tissue damage repair process?
- 1: injury and early and late phases of inflammation
- 2: granulation tissue formation and epithelial growth
- 3: matrix formation and remodeling
Platelet aggregation and blood coagulation results in hemostasis. Fibrin clot formation provides the matrix for amcrophages, fibroblasts, and capillary migration. Activation of blood complement cascade which induces formation of bradykinin (induces vasodilation and pain).
Acute inflammation - Chemotaxis?
complement cascade produces proteins that attract neutrophils (white blood cells) and monocytes (activate into marcophages). These stimulate the release of vasoactive modulators (histamine and leukotrienes) from mast cells.
Two parts of the inflammatory process?
Vascular and cellular response. Defent body against alien substances (immunological response), dispose of dead tissue, and increase blood flow.
What is diapedesis and what does it result in?
the outward passage of blood cells through intact vessel walls (leakage between endothelial cells).
Results in influx of plasma proteins that facilitate edema.
Five cardinal signs of inflammation?
- Loss of function
5 steps of the early inflammatory phase?
- 1.) Adherence
- 2.) Diapedesis
- 3.) Phagocytosis
- 4.) Oxygen radical processing of material
- 5.) Exocytosis of processed waste
What marks the end of the early phase of inflammation?
The activation of monocytes into macrophages
What is late phase inflammation characterized by?
Role of macrophages in the inflammation process?
Macrophages continue phagocytosis of pathogens and wound debris and release many biologically active substances which initiate granulation tissue formation
Is inflammation necessary for wound repair?
YES. it is required to initiate subsequent stages of repair. The pharmacological reduction of inflammation may actually slow the wound repair process.
What happens if the inflammatory phase persists?
Can result in significant tissue damage beyond what was caused by the initial injury.
What causes chronic inflammation and what does it result in?
Persistence of macrophages due to replication rather than chemotaxis. Results in blockade of repair.
What happens during the Granulation Phase?
- Dense population of macrophages (clean up) and fibroblasts (synthesis of new components).
- Proliferation of epithelial cells.
- Formation of loose matrix of collagen fibers and ground substance
- angiogenesis (neovascularization)
- wound contraction
What causes re-epithelization in the granulation phase?
- Proliferation and migration of epithelial cells from the edge of the wound (Free-edge effect). Process continues until the wound site is completely covered.
- new epithelial cells keratinize setting off a strong inflammatory response in the connective tissue below. Migration of the epithelial cells separates the scab from the wound bed and the scab falls off.
What happens during the tissue formation stage of granulation?
- Fibroblasts enter the wound area and deposit loose extracellular matrix, then initiate collagen sunthesis and extracellular formation of collagen fibers.
- Collagens are a family of triple-chain glycoproteins that polymerize side by side and end to end.
- Fibroblasts also secrete ground substance between the collagen fibers (= granulation tissue)
What happens during the neovascularization phase of granulation?
- Angiogenesis occurs simultaneously with fibroplasia and is driven by low oxygen tension, growth factors, lactic acid accumulation, and biogenic amines.
- The new capillary loops are very fragile so great care must be taken when working with new granulation tissue during cllinical wound care.
Fibroblasts develop large actin bundles (myofibroblasts) and induce contraction of the dermis.
What happens after wound contraction?
the tissue surrounding the wound is thinner, stretched, and under tension. Great care must be taken with contracted tissue.
What happens during the matrix production/remodeling phase?
Dissolution of the recently formed granulation tissue. Matrix re-sculpting and accumulation of large fibrous bundles of collagen. Change in the composition of the ground substance. These changes increase the tensile strength of the scar, but never as strong as the original tissue.
Describe matrix maturation.
Fibronectin and hyaluronic acid are removed. Collagen bundles grow in size, increasing mound tensile strength. Proeoglycans are deposited adding resilience to deformation.
What happens to the amount of vascularization during tissue remodeling?
decreases so the mature scar has a low blood supply (change in color from pink to white)
Final strength of scar vs. original tissue?
only 70% the strength of the original tissue
how is collagen oriented prior to remodeling phase vs after?
in a random fashion before, oriented along the lines of applied tension after. This results from performance of functional activity
What happens during the remodeling phase if the equilibrium between collagen synthesis and degradation is not balanced?
see hypertrophic or keloid scars
Role of oxygen in wound healing?
Initially the wound is hypoxic because of vasoconstriction and clot formation. inflammation greatly increases blood flow and oxygenation. Inflammation also induces an influx of many new cells resulting in hypoxia, hypercarbia, and acidosis. Collagen synthesis and polymerization is an oxygen requiring process so any process that reduces oxygen uptake will reduce the rate of healing (ex: smoking, anemia, lung disease).
At what age is wound healing slower?
inflammatory response, wound re-epithelization, and cound contraction are all delayed in the elderly
Aside from wound healing, what else do the elderly face?
- delayed cellular migration.proliferation
- delayed metabolic response
- delayed biosynthetic response