Tissue Repair Flashcards
What are the two types of regeneration?
Regeneration-growth of cells and tissues to replace lost structures
and
Healing with scar-When complete restitution not possible since supporting structures everely damaged and/or injured tissues are incapable. Usually collagen deposition (fibrosis) provides structural support
what organs regenerate vs. heal with scars
Regeneration:
Skin, Liver, Intestinal
Healing with scar:
Severe/chronic damage in lung, liver kidneys etc.
What are the 3 types of cell renewel tissues and what types of organs are associated with each?
- Labile- Continuous renewal
Hematopoietic cells in marrow, surface epithelia, mucosal epithelia (ducts, g.i., bladder respiratory, etc.)
- Stable- Parenchyma of most solid organs
Pancrease, adrenal, lung, thyroid, kidney, also liver (except liver has more regenerative capabilities, fxnal mas not form) also almost all hepatocytes participate during regeneration not stem cells.
- Non-dividing cells- repair by connective tissue
Neurons, cardiac myofibers
What are the 4 growth factors involved in repair?
- VEGF (Vascular endothelial growth factors)*
- FGF (Fibroblast growth factors)*
3. PDGF (Platelet-derived growth factors)
4. TGF-beta (Transforming growth factor-beta)
Source and fxn of VEGF?
Mesenchymal cells
induces angiogenesis in injury and in tumors (stimulates endothelial cells)
Source and fxn of FGF?
Macrophages, mast cells, endothelial cells, fibroblasts, and more
Induces angiogenesis; promotes migration of fibroblasts, epithelial cells, and macrophages
Source and fxn of PDGF?
Platelets, macrophages, endothelial cells, smooth muscle cells epithelium
Induces fibroblast, smooth muscle, endothelial cell proliferation & migration; stimulates production of ECM
Source and fxn of TGF-beta
Platelets, endothelium, epithelium, lymphocytes, macrophages, smooth muscle cells, fibroblasts.
Suppresses endothelial proliferation/migration & acute inflammation; stimulates production of ECM proteins
What are the 2 basic forms of ECM?
Interstitial matrix: a 3-D amorphous gel
Basement Membrane: highly organized interstitial matrix present around epithelial cells, endothelial cells, & smooth muscle cells.
What synthesizes interstitial matrix
Fibroblasts
What synthesizes basement membrane
Mesenchyme and epithelium
What is the role of the extracellular matrix ECM?
- Mechanical support
- Regulate cell proliferation (through integrins)
- Provides scaffold essential for healing without scar
- Storage of growth factors: fibroblast growth factor, hepatocyte growth factor
- Creates a “microenvironment”
What are the components of ECM
I. Fibrous structural proteins:
Collagen and Elastin
II. Proteoglycans & hyaluronan-
Highly hydrated gels that provide compressibility and contain growth factors
III. Adhesive glycoproteins & receptors:
Fibronectin (major component of interstitial ECM), Laminin (Major component of basement membrane), Adhesion molecules (cell adhesion molecules CAMs)
What is collagen?
Structural proteins providing tensile strength
What is elastin?
Forms elastic fibers with fibrillin allowing for recoil
What is the cause of Ehlers-Danlos syndrome (EDS)
Genetic defects in collagen synthesis or structure
What are the common clinical features of Ehlers-Danlos syndrome?
Tissues containing the type of affected collagen lack tensile strength:
- Skin-hyperextensible, fragile, and easily traumatized
- Joints and ligaments are hypermobile
- Rupture of internal organs (colon) & large arteries
- Poor wound healing
* Classic type results in deficient production of collagen type V
What is Marfan syndrome? What are some of the symptoms/findings?
Mutation affecting fibrillin.
- Degeneration of aorta:aneurysm and dilatation
- Dislocated lens
- Abnormalities of aortic and mitral valves
- Long legs, arms, fingers
- Hyper-extensible joints
What is Fibrillin and where is it present?
The major component of microfibrils in ECM, widely distributed in body and abundant in: AORTA, LENS, LIGAMENTS
When does repair by connective tissue (scar formation) occur?
Severe/chronic injury with destruction of stroma.
Injury of non-dividing cells
What are the steps of repair by connective tissue (Scar formation)?
- Angiogenesis
- Fibroblast migration and proliferation
- Extracellular matrix deposition (scar formation)
- Maturation of fibrous tissue (remodeling)
When is granulation tissue present? What is it and what does it contain?
3-5 days.
Specialized tissue seen in healing.
Contains new vessels, inflammatory cells, and fibroblasts.
What are the important growth factors for Angiogenesis?
VEGF and FGF
Where does angiogenesis come from? And what are the important key points of each?
- From pre-existing vessels
Vasodilatation: Nitric oxide (NO), vascular endothelial growth factor (VEGF)
Migration
Proliferation
Eventual inhibition and remodeling
- From endothelial precursor cells (angioblasts) in bone marrow
Neovascularization of ischemic organs, wounds and tumors, and re-endothelialization of grafts
What are the important growth factors for fibroblast migration and proliferation and deposition of ECM?
**TGF-beta **
PDGF
FGF
What occurs in the maturation of fibrous tissue?
Decreased vessels and some degradation of collagen and other extracellular matrix proteins.
What accomplishes the degradation of collagen and other ECM proteins during the maturation of fibrous tissue? What is it secreted by
Matrix metalloproteinases (MMP) containing zinc.
Secreted by several cell types: fibroblasts, macrophages, neutrophils etc.
What is wound strength at the end of the first week?
10%
What are the steps to cutaneous wound healing?
3 phases;
- Inflammation
- Granulation tissue formation and re-epithelialization
- Wound contraction, ECM deposition, and remodeling
Steps of healing by First Intention (or Primary Union) and timeframe
- Immediate*- Incisional space fills with clotted blood
- Within 24 hrs*- Neutrophils appear at margin of wound, beginning of re-epithelialization
- By day 3*- Neutrophils replaced by macrophages and granulation tissue fills incisional space
- By day 5*- Maximal granulation tissue and Collagen fibers begin to bridge incision
- Weeks*-Scar: connective tissue without inflammation;decreased vessels
When does healing by Secondary Intention/Secondary union occur?
When more extensive damage leaves a tissue defect: large wounds, abcesses, ulceration.
When does wound strength rapidly increase and when does it plateau and to what extent of wound strength?
10% at end of first week.
Rapid increase in wound strength over the next four weeks
Plateaus by 3rd month at 70-80%
Factors influencing healing
Nutrition- Vitamin C deficiency inhibits collagen synthesis
Metabolic status- Diabetic patients have impaired neutorphil and macrophage functions, impaired new vessel formation, impaired collagen synthesis, all leading to persistence of ulcers and infections.
Circulatory status- Poor perfusion or obstructed venous drainage prevents in-flow of needed cells/proteins
Hormones-Steroids inhibit TGFbeta and decreases fibrosis
Infections- Prolongs inflammation and may increase local tissue injury
Mechanical factors- Increased local pressure may lead to dehiscence (rupture of surgical incision or closed wound)
Foreign bodies- Prolongs inflammation
Types of wound healing complications
- Deficient scar formation- Dehiscence and ulceration like on diabetic patients
- Excessive repair component formation- Keloid (raised scar due to excess collagen) and Exuberant graulation (protrudes above surrounding skin and prevents re-epithelialization).
- Formation of contractures- Excessive contraction resulting in deformity of wound/surrounding tissue such as afer serious burns
What is the mechanism of keloids?
Not completely understood but
Increased activity of TGF-beta and IL-1 (fibrogenic cytokines) has been described.
Heritable and African-Americans have increased risk.
