[P] Week 2: Inflammation and Repair - Part 3 Flashcards
TISSUE REPAIR
What is repair in the context of tissue?
Repair, also called healing, refers to the restoration of tissue architecture and function after an injury.
TISSUE REPAIR
What initiates the healing process after tissue injury?
Injury to cells and tissues sets in motion a series of events that contain the damage and initiate the healing process.
TISSUE REPAIR
What are the two processes involved in the repair of damaged tissues?
regeneration, which restores normal cells, and scarring, the deposition of connective tissue.
TISSUE REPAIR
What factors influence the repair process?
The repair process depends on type of wound, inflammatory process, matrix damage, and organ.
CELL AND TISSUE REGENERATIO
What is complete healing of an organ?
It is a complete healing of the organ (ex. wound, injury)
Example: Healing of a cut on the skin.
CELL AND TISSUE REGENERATIO
What does regeneration involve?
Involves proliferation of cells and tissues.
CELL AND TISSUE REGENERATIO
What is replaced during regeneration?
Replacement of structure and function.
CELL AND TISSUE REGENERATIO
Which organs in the body may regenerate?
Liver, kidney, epithelia of skin and GIT.
TISSUE PROLIFERATIVE ACTIVITY
Tissue of the body are divided into 3 groups on the basis of proliferative activity of their cells, enumerate
- Labile tissues (continuously dividing)
- Quiescent tissues (stable)
- Permanent tissues (non-dividing)
TISSUE PROLIFERATIVE ACTIVITY
continuously dividing cells that proliferate throughout life, replacing those that are destroyed.
Labile tissues (continuously dividing
Examples include surface epithelia, squamous cells (skin, oral cavity, vagina, cervix), lining of excretory ducts, columnar epithelium (GIT, endometrium), and transitional epithelium (GUT).
TISSUE PROLIFERATIVE ACTIVITY
Where are labile cells found?
Labile cells can be found in bone marrow and in hematopoietic tissues.
TISSUE PROLIFERATIVE ACTIVITY
low level of replication but can undergo rapid division in response to stimuli, allowing them to reconstitute the tissue of origin.
Quiescent tissues (stable)
Examples include parenchymal cells (liver, kidneys, pancreas), fibroblasts, smooth muscle cells, chondrocytes, osteocytes, and endothelial cells.
TISSUE PROLIFERATIVE ACTIVITY
lining epithelium of a blood vessel but are not labile cells; they proliferate only when there is an injury.
Endothelial cells
TISSUE PROLIFERATIVE ACTIVITY
consist of cells that have left the cell cycle and cannot undergo mitotic division in postnatal life.
Permanent tissues (non-dividing
Examples include cardiac muscle, skeletal muscle, and neurons.
MECHANISMS OF TISSUE & ORGAN REGENERATION
Mammals cannot regenerate whole tissues or organs because of the following reasons, enumerat
- No blastema formation
- Rapid fibroproliferative response after injury
- Wnt/β-catenin is highly conservative
LIVER REGENERATION
TOF
The human liver has a remarkable capacity to explode.
F - regenerate
LIVER REGENERATION
How is liver mass restored after resection?
Restoration of liver mass is achieved without the regrowth of the lost lobes that were resected.
more of a compensatory growth
LIVER REGENERATION
What are the two major mechanisms of liver regeneration?
Regeneration of the liver occurs by:
- proliferation of remaining hepatocytes
- repopulation from progenitor cells
LIVER REGENERATION
What triggers hepatocyte proliferation in the regenerating liver?
Hepatocyte proliferation is triggered by the combined actions of cytokines and polypeptide growth factors.
Do all hepatocytes replicate during liver regeneration?
Almost all hepatocytes replicate during liver regeneration after partial hepatectomy.
What happens if repair cannot be accomplished by regeneration alone?
Repair occurs by replacement of the injured cells with connective tissue, leading to the formation of a scar, or by a combination of regeneration of some residual cells and scar formation.
Steps in repair
- Scar formation and fibrosis
o First, there is injury in the area. There may be bleeding and scab formation, followed by inflammation. - Inflammation
- Angiogenesis
- Migration and Proliferation of Fibroblasts
- Scar Formation
- Connective Tissue Remodeling
process of new blood vessel development from existing vessels
ANGIOGENESIS
what are the types of Angiogenesis
- Vasculogenesis
- Angiogenesis or Neovasculrization
ANGIOGENESIS
It is the formation of new blood vessels assembled during embryonic development.
Vasculogenesis
They may start from cells like angioblasts or hemangioblasts.
ANGIOGENESIS
Vasculogenesis may start from?
angioblasts or
hemangioblasts
ANGIOGENESIS
It is the formation of new vessels in adults; these are already coming from a well-formed vessel and may appear as branching or extending.
Angiogenesis or Neovascularization
ANGIOGENESIS
stable cells; once they are needed, they can proliferate.
Endothelial cells
Initially, endothelial cells are on a low level of replication, however, once needed, they will undergo replication.
MECHANISMS OF ANGIOGENESIS
What initiates angiogenesis from endothelial precursor cells?
The endothelial progenitor cells (EPC) from bone marrow initiate angiogenesis.
EPCs are similar to angioblasts and hemangioblasts.
MECHANISMS OF ANGIOGENESIS
It involves vasodilation, degradation of bone marrow, proliferation and migration of endothelial cells, maturation of endothelial cells, and recruitment of periendothelial cells.
From pre-existing cells
MECHANISMS OF ANGIOGENESIS
What happens during angiogenesis in adults from pre-existing vessels?
undergo vasodilation and degrade the basement membrane to release endothelial cells that will subsequently proliferate.
MECHANISMS OF ANGIOGENESIS
What occurs after the proliferation of endothelial cells in angiogenesis?
Once the vessels proliferate, it will initialize the new vessel; further, new periendothelial or perivascular structures will form.
GROWTH FACTORS AND RECEPTORS INVOLVED IN
ANGIOGENESIS
What is the most important growth factor involved in angiogenesis?
Vascular endothelial growth factor (VEGF)
GROWTH FACTORS AND RECEPTORS INVOLVED IN
What induces VEGF?
induced by hypoxia, TGF-β, PDGF, and TGF-α.
GROWTH FACTORS AND RECEPTORS INVOLVED IN
What are the functions of VEGF?
- Promote angiogenesis
- Increase vascular permeability
- Stimulate endothelial cell migration and proliferation
ECM REGULATES ANGIOGENESIS
ECM proteins participate in vessel sprouting through interactions with ____ ____ in endothelial cells and by providing a scaffold for vessel growth.
integrin receptors
ECM REGULATES ANGIOGENESIS
What role do integrins play in angiogenesis?
formation and maintenance of newly formed blood vessels.
ECM REGULATES ANGIOGENESIS
degrade the ECM to permit remodeling and extension of the vascular tube.
matrix metalloproteinases (MMPs)
ECM REGULATES ANGIOGENESIS
How do matricellular proteins affect angiogenesis?
destabilize cell-matrix interactions, promoting angiogenesis.
ECM REGULATES ANGIOGENESIS
Proteinases, like ____ ____ cleave
extracellular proteins, releasing matrix-bound growth factors.
Plasminogen activators
ECM REGULATES ANGIOGENESIS
What is necessary for the stabilization of newly formed vessels for stabilization
pericytes, smooth muscle cells, and the deposition of connective tissue.
ECM REGULATES ANGIOGENESIS
The newly formed vessels are fragile and need to be stabilized through the recruitment of pericytes and
smooth muscles and by the deposition of ECM proteins— what are the ECM proteins
angiopoietin 1 and 2, PDGF, and TGF-β
CUTANEOUS WOUND HEALING
What occurs initially in the inflammation phase of cutaneous wound healing?
Clot formation
CUTANEOUS WOUND HEALING
What is the histologic hallmark of healing in the proliferation phase?
Granulation tissue formation
CUTANEOUS WOUND HEALING
What are the components of granulation tissue?
- neovascularization
- angiogenesis
- proliferation of fibroblasts
CUTANEOUS WOUND HEALING
What role does granulation tissue play in wound healing?
Granulation tissue provides a provisional matrix for healing.
CUTANEOUS WOUND HEALING
What follows granulation tissue formation in the healing process?
Collagen deposition and fibrosis
HEALING OF SKIN WOUNDS
When the injury involves only the epithelial layer, the principal mechanism of repair is epithelial regeneration,
Primary Union (Healing By 1st Intention
HEALING OF SKIN WOUNDS
- Involves excisional wounds, like ulcer. Even if it is cleaned or sutured, there are still presence of large spaces, as compared to incisional wound.
- Excisional wounds are associated with intense inflammatory reaction
Secondary union (Healing By 2nd Intention)
HEALING OF SKIN WOUNDS
Excisional wounds are associated with?
intense inflammatory reactions
HEALING OF SKIN WOUNDS
Why is inflammation more intense in excisional wounds?
due to larger tissue defects having greater volumes of necrotic debris, exudate, and fibrin that must be removed.
HEALING OF SKIN WOUNDS
What is the consequence of large tissue defects?
Large defects have a greater potential for secondary, inflammation-mediated injury.
HEALING OF SKIN WOUNDS
What happens to granulation tissue in secondary union?
Much larger amounts of granulation tissue are formed to fill the bigger gap caused by the larger area of deficit.
HEALING OF SKIN WOUNDS
What is the relationship between granulation tissue and scar tissue?
A greater volume of granulation tissue generally results in a greater mass of scar tissue.
HEALING OF SKIN WOUNDS
What may be seen with substantial scar formation?
accompanied by thinning of the skin surface or epidermis.
HEALING OF SKIN WOUNDS
helps to close the wound by decreasing the gap between its dermal edges and reducing the wound surface area
Wound contraction
HEALING OF SKIN WOUNDS
the formation of a network of myofibroblasts, which are modified fibroblasts with contractile properties.
Wound contraction
WOUND STRENGTH
What is the wound strength of carefully sutured wounds compared to normal skin?
Carefully sutured wounds have approximately 70% of the strength of normal skin, largely because of the placement of sutures.
WOUND STRENGTH
he recovery of tensile strength results from the excess of collagen synthesis over collagen degradation during the first 2 months of healing by?
cross-linking of collagen fibers and increased fiber size
WOUND STRENGTH
What percentage of normal strength do wounds reach by 3 months?
Wound strength reaches approximately 70% to 80% of normal by 3 months but usually does not substantially improve beyond that point.
What are the Systemic factors affecting the wound Healing
- Nutrition (Protein, Vitamin C)
- Metabolic Status (Diabetes)
- Circulatory Status (Arteriosclerosis)
- Hormones (Glucocorticoids)
What are the local factors affecting the wound healing
- infection
- Mechanical Factors
- Foreign Bodies
- Size, Location and Type of wound
COMPLICATIONS IN CUTANEOUS WOUND HEALING
What are the types of complications in cutaneous wound healing?
a) Deficient scar formation
b) Excessive formation of the repair components
c) Formation of contractures
COMPLICATIONS IN CUTANEOUS WOUND HEALING
What does deficiency in repair components lead to?
It leads to inadequate formation of granulation tissue, resulting in opening of the wound with dehiscence and ulceration.
EXCESSIVE SCARRING
Grossly, the deposition in a hypertrophic scar is within the border of the wound.
Hypertrophic Scars
EXCESSIVE SCARRING
Grossly, the deposition in a keloid may extend out of the border of the
wound.
Keloid
EXCESSIVE SCARRING
Microscopically, the deposition of collagen in a hypertrophic scar is
parallel to the skin surface.
Hypertrophic Scars
EXCESSIVE SCARRING
Microscopically, the
deposition of collagen in
a keloid is haphazard
Keloid
the formation of excessive amounts of granulation tissue that protrudes above the level of the surrounding skin and blocks reepithelialization.
Exuberant granulation
This process has been called, with more literary fervor, proud flesh.
EXUBERANT GRANULATION
How must excessive granulation be treated?
removed by cautery or surgical excision to permit restoration of the continuity of the epithelium.
EXUBERANT GRANULATION
are neoplasms that lie in the interface between benign and malignant (though low-grade) tumors.
Desmoids, or aggressive fibromatoses,
EXUBERANT GRANULATIONExuberant granulation
What can exaggeration of contraction lead to?
An exaggeration of contraction gives rise to contracture, resulting in deformities of the wound and the surrounding tissues.
When are contractures commonly seen?
after serious burns and can compromise the movement of joints.