Wound Healing and Repair Flashcards
Define parenchyma
organ specific cells related to the function
E.g. Parenchyma of the Kidney – Epithelial tissue (renal tubes)
Parenchyma of the Heart – Muscle Tissue (Cardiac muscle cells)
Define Stroma
‘Background’ tissue - provides the structure, mechanical and nutritional support to the organ
Distinguish between the two types of connective tissue
Loose Connective tissue – contains numerous cells, loose fiber arrangement in a viscous matrix
E.g. Haemopoietic/lymphatic tissue
Dense irregular connective tissue – dense woven network of collagen and fibers in a viscous matrix
E.g. joint capsules, tendon and ligaments
Define a wound
Injury/ trauma to tissues
Disruption of the function and structure of tissue
Define healing
Process of returning to health
Restoration of structure and function of injured/diseased tissues
Outline the stages of wound healing
- Haemostasis process - wound closed by clotting (coagulation process), platelets and fibrin adhere, formation of a thrombus - <24h
- Inflammatory process - platelets control bleeding, macrophages prevent infection, neutrophils (inflammation) - 0-4days
- Proliferative process - Angiogenesis, epithelialisation, contraction, fibrous tissue formation - 1-14 days
- Remodeling process - maturation phase, collgen is remodeled and becomes realigned, injured sites tend to be weaker than normal sites (80% tensile strength) - 21days - years
what is meant by resolution?
- clearance of injurious stimuli
- clearance of mediators and acute inflammatory cells
- replacement of injured cells
- normal function
Desctibe the possible outcomes after injury and inflammation
What is meant by tissue repair?
The restoration of structure and function of damaged tissue
What are the 2 types of reactions that occur in tissue repair (healing)?
Regeneration
Scar formation
What is regeneration?
What is it driven by?
- Healing in which new growth completely restores portions of damaged tissue to their normal state
- Driven by growth factors such as PDGF, VEGF, and TGF-Beta
- ECM plays a major function in regeneration
What is meant by a labile tissue?
Give examples
Continuously proliferating in order to replace dead or sloughed-off cells
E.g. skin, gastrointestinal, salivary gland tissue
What is meant by a stable tissue?
Give examples
Cells that normally exist in a non-dividing state but may enter the cell cycle in response to certain stimuli, such as cell injury
E.g. Parenchymal cells of the liver, kidney and pancreas
What is meant by permanent tissue?
Give examples
Non-dividing cells, leads to scar formation
E.g. Cardiac and skeletal
What role do growth factors have in regeneration?
- Proteins that stimulate survival, proliferation of particular cells, may also promote migration and differentiation
- Produced mainly by macrophages and lymphocytes at the site of injury as part of the inflammatory process.
- Other growth factors are produced by parenchymal cells or stromal (connective tissue) cells in response to cell injury
- Stimulate entry of cells into cell cycle
- Produced transiently in response to an external stimulus and act by binding to cellular receptors
- E.g. EGF, TGF-alpha, VEGF anf FGF
What is the role of ECM in regeneration?
- Stores and presents growth factors
- acts as a scaffold to which migrating cells can adhere
What is scar formation and when does it occur?
- Replacement of damaged parenchymal cells with connective tissue
- Incomplete restoration of architechture and function
- Occurs in: Severe or chronic injuries that result in damage of parenchymal cells as well as connective tissue (scaffolding) and Permanent non-dividing tissues
What are the stages of scar formation?
- Tissue injury
- Inflammation
- Formation of granulation tissue
- Scar formation
What is angiogenesis?
- The process of new blood vessel development
- Involves sprouting of new vessels from existing ones - involved proliferation and migration of endothelial cells
- Derived by GF e.g VEGF
- Critical in healing at sites of injury and in the development of collateral circulations at sites of ischaemia
How does granulation tissue form?
Occurs in two steps:
- Migration and proliferation of fibroblasts into the site of injury
- Deposition of ECM proteins produced by these cells
Derived by GF e.g. TGF-Beta, PDGF and FGF
New connective tissue together together with new blood vessels has pink granular appearance - Granulation tissue
What is remodeling?
Connective tissue in the scar continues to be modified and remodeled to improve the tensile strength of the wound
The outcome of the repair process is a balance between synthesis and degradation of ECM proteins
The degradation of collagens and other ECM components is accomplished by a family of matrix metalloproteinases
Wound strength reaches approx. 70-80% of normal by 3 months and usually does not improve substantially beyond that
Give 3 examples of tissue repair
Healing of skin wound
Healing of bone fractures
Fibrosis in internal organs
What does skin wound healing usually involve and how does it occur?
Skin wound healing involves both epithelial regenration and the formation of connective tissue scar
Depending on nature and size of the wound, healing occurs by
First intention (Primary union)
Second Intention (Secondary union)
Give an example of healing by first intention
Healing of a clean, uninfected surgical incision approximated by surgical sutures
What is the principal mechanism of repair in first intention?
Epithelial regeneration
Describe how healing by first intention occurs
- Narrow incisional space fills with fibrin-clotted blood (Scab)
- Neutrophils are seen at the incision margin, migrating towards fibrin clot within 24 hours (acute inflammation)
- Epithelial cells from both edges begin to migrate and proliferate along the dermis within 24-48 hours
- Day 3-7 : Neutrophils largely replaced by macrophages, angiogenesis reaches its peak. Granulation tissue progressively invades the incision space
- During second week, there is continued collagen accumulation and fibroblast proliferation (scar maturation)
- Remodeling of the scar continues for months aiming to increase wound tensile strength
Give examples of healing by second intention
- Large wounds at sites of abscess formation
- ulceration
- infarction
Outline healing by second intention
The repair process is more complex and involves development of abundant granulation tissue, with accumulation of ECM and formation of a large scar
Scar formation is followed by wound contraction mediated by the action of myfibroblasts.
How is secondary healing different from primary healing?
- A larger clot or scab
- Inflammation is more intense because large tissue defects have a greater volume of necrotic debris, exudate, and fibrin that must be removed
- Larger defects require a greater volume of granulation tissue to fill in the gaps - greater mass of scar tissue
- Secondary healing involved wound contraction - within 6 weeks large skin defects may be reduced to 5-10% of their original size
Name the stages of fracture healing
- Haematoma
- Granulation tissue
- Callus
- Woven bone
- Lamellar bone
- Remodelling
What is fibrosis?
Excessive deposition of collagen and other ECM components in a tissue
Basic mechanisms are the same as those of scar formation during tissue repair
Fibrosis seen in chronic diseases is often responsible for organ dysfunction and even organ failure E.g. RA pannus formation & ankylosis, pulmonary fibrosis
Name some local factors affecting tissue repair
- Infection
- Mechanical factors - increase local pressure/torsion may cause wound to pull apart
- Foreign bodies
- Size of wound
- Location of wound
- Type of wound - complete restoration can only occur in tissues composes of stable and labile cells - injuries to tissues composed of permanent cells must result in scarring e.g. MI
Name some systemic factors affecting tissue repair
- Nutritional status - protein deficiency, vitamin C deficiency inhbit collagen synthesis and delay healing
- Metabolic status
- Circulatory status - poor perfusion due to ateriosclerosis/diabetes or obstructed venous drainage (varicose veins) impairs healing
- Hormones
- Age
- Collagen disorders
What is the most important cause of delay in healing and why?
INFECTION
It prolongs inflammation and potentially increases the local tissue injury
Name the 3 main complications of tissue repair
- Inadequate formation
- Excessive formation
- Formation of contracture
What is inadequate formation in tissue repair?
Rupture or dehiscence - separation of the layers of the surgical wound
Evisceration - extrusion of viscera outside the body through a surgical incision
Ulceration - A lesion through the skin or a mucous membrane resulting from loss of tissue, usually with inflammation
What is excessive formation in tissue repair?
Keloid formation - accumulation of excess amounts of collagen , giving rise to raised scars
May also generate exuberant granulation tissue that protrudes above the level of the surrounding skin and hinders epithelialistion (“proud flesh”)
What are contractures in tissue repair?
- Contractures - fibrosis of connective tissue in skin, fascia, muscle or a joint capsule that prevents normal mobility of the related tissue or joint
- Myofibroblasts play a major role in their pathogenesis
E.g. Severe burns, neurologic conditions -stroke/nerve damage
