Tissue Renewal And Repair: Regeneration, Healing And Fibrosis Flashcards
Repair of damaged tissues occurs by two types of reactions
Regeneration
Connective tissue deposition
Regeneration
Proliferation of uninjured residual cells
Maturation of tissue stem cells
Involves cell proliferation
Driven by growth factors
Dependent on the integrity of the extracellular matrix and by the development of mature cells from stem cells
Scar formation
Deposition of connective tissue to form a scar
Injured tissues are incapable of complete restitution
Ability of tissues to repair themselves determined by
Their own intrinsic proliferative capacity
Which cell types proliferate during tissue repair
Remnants of the injured tissue
Vascular endothelial cells
Fibroblasts
Features of the Labile tissues
Continuously dividing tissues
Replaced by maturation from stem cells
Pool of stem cells needs to be preserved for regeneration
Where Labile tissues found at
Hematopoietic cells—> Bone marrow
Surface epi—> Skin,Oral cavity, Vagina, cervix
Cuboidal epi of —> ductus draining exocrine organs
Columnar epi of—> GIT,uterus and Fallopian tubes
Transitional epi of—> urinary tract
Features of Stable tissues
Not proliferating tissues
Capable of dividing in response to injury or loss of tissue mass
Cells in the G0
Can proliferate in response to growth factors
Where are stable tissues found at
Most solid organs= Liver, Kidney,Pancreas
Endo cells
Fibroblasts smooth muscle cells
Features of permanent tissues
Consist of terminally differentiated nonproliferative cells
Injury to these is irreversible
Results in scar formation
Where are permanent tissues found at
Majority of neurons
Cardiac muscle cells
*skeletal muscle cells
Cell proliferation is driven by which signals
Growth factors
From the extracellular matrix
Features of the Growth factors
Chemical mediators
Promote cell survival and proliferation
Some act on multiple types
Some act as cell specific
Produced by cells near the site of damage
**most important source is macrophages
Epi and stromatol cells also produces GFs
Paracrine signaling
Result of Growth Factors
Expands cell population by stimulating cell division and increase in cell size
Importance of ECM-Cell Matrix interactions
Regulates proliferation, movement and differentiation of the cells
Important role in wound healing, chronic fibrotic processes,tumor invasion and metastasis
Main components of ECM
Basement membrane
Interstitial matrix
Which structure act as a Reservoir for GFs
ECM
Cell and tissue regeneration in intestine and skin
Injured cells are rapidly replaced by proliferation of residual cells
Differentiation of cells derived from tissue stem cells
Cell and tissue regeneration in Bone Marrow
Driven by GFs called colony-stimulating factors
Cell and tissue regeneration in parenchyma organs
Generally limited process
Except LIVER
Kidney removal elicits compensatory response (hypertrophy + hyperplasia) in the contralateral kidney.
Regeneration of the liver occurs by two major mechanisms
1-Proliferation of remaining hepatocytes
2- Repopulation from progenitor cells
When repair cannot be accomplished by regeneration alone in severe or chronic injury
When the CT framework gets damaged
Nondividing cells are injured
Replacement of the non regenerated cells needs to be done by
CT
Main steps in repair by scarring
Clot formation
Inflammation
Angiogenesis and formation of granulation tissue
Migration and proliferation of fibroblasts,collagen synthesis
CT remolding
What is Angiogenesis
Process of new blood vessel development from existing vessels
Molecules that are involved in Angiogensis
Growth factors= VEGFs,FGFs
Notch signaling
ECM proteins
Enzymes= Matrix metalloproteinases
**What is the most important cytokine for the synthesis and deposition of CT proteins
TGF-beta
**In Granulation tissue which molecule is not prominent
Collagen
In tissue remodeling why formation of scar is seen
Scar remodeled to increase its strength and contract it
With time CT will be degraded and the scar will shrink
2 classifications of healing of skin wounds
1-First intention (primary union) = epi regeneration with minimal scarring
2-Second intention (secondary union) = larger wounds heal by combination of scarring and regeneration
Pathological aspects that effects repair
Infection
Diabetes
Nutritional status
Glucocorticoids
Mechanical factors
Poor perfusion
Foreign bodies
Type and extend of tissue injury
Location of the injury
Examples of Chronic Wounds
Venous leg ulcers
Arterial ulcers
Pressure sores
Diabetic ulcers
Excessive scarring examples
Hypertrophic scar
Keloid
Wound contracture
Examples of Fibrosis in Parenchymal organs
Scleroderma
Idiopathic pulmonary fibrosis
Liver cirrhosis
End stage kidney disease
Constrictive pericarditis
