Healing and Repair Flashcards by Steven Marincel

What is karyorrhexis?

nucleus broken up into multiple pieces (fragmentation)

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What is pyknosis?

ink dot nucleus

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What is karyolysis?

loss of nucleus

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What are the two ways that healing can occur?

regeneration or scar formation

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What is regeneration?

replacement of damaged cells by replication of the same cell type

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What is scar formation?

replacement of damaged cells by connective tissue

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What has to remain intact for cells to regenerate?

the connective tissue scaffolding (ECM)

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What is the protein composition of ECM?

Fibrous structural proteins (elastin, collagen)

Hydrated gels (proteoglycan, hyaluronan)

Adhesive glycoproteins

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What is the replication status of labile tissues? What are the lost cells replaced by in these tissues?

continuously dividing tissues, lost cells can be replaced by maturation of stem cells or proliferation of mature cells

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What is the replication status of stable tissues?

Low or no replication - in G0, but can rapidly divide if stimulated

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What are permanent tissues? Give two examples

Terminally differentiated, nonproliferative in postnatal life.

Brain, Heart

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What are the sources of EGF?

Activated macrophages, keratinocytes, others

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What are the functions of EGF?

Mitogenic for keratinocytes and fibroblasts

Stimulates keratinocyte migration

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What are the sources of TGF-alpha?

Activated macrophages, keratinocytes, others

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What are the functions of TGF-alpha?

stimulates proliferation of hepatocytes and other epithelial cells

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What are the sources of VEGF?

Mesenchymal cells

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What are the functions of VEGF?

Stimulates proliferation of endothelial cells

Increases vascular permeability

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What are the sources of PDGF?

Platelets, macrophages, endothelial cells, keratinocytes, smooth muscle cells

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What are the functions of PDGF?

Chemotactic

Activates and stimulates proliferation of fibroblasts and endothelial cells

Stimulates ECM protein synthesis

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What are the sources of FGFs? (fibroblast growth factors)

Macrophages, mast cells, endothelial cells, others

What are the functions of FGFs?

Chemotactic

Mitogenic for fibroblasts

Stimulates angiogenesis, ECM protein synthesis

What are the sources of TGF-beta?

Platelets, macrophages, endothelial cells, fibroblasts

What are the functions of TGF-beta?

Chemotactic for leukocytes and fibroblasts

Stimulates ECM synthesis

Suppresses acute inflammation

What does VEGF do?

Promotes angiogenesis, increases vascular permeability, stimulates endothelial cell migration and proliferation

Where are two locations where VEGF has high expression?

podocytes in glomeruli pigment epithelium of retina

What is an important inducer of VEGF?

hypoxia

What do fibroblasts do?

synthesize connective tissue proteins

What are the growth factors that drive recruitment and growth of fibroblasts?

PDGF, FGF, TGF-beta

What is granulation tissue?

Specialized tissue that fills in defects in organs when non-regenerative cells and/or connective tissue framework is destroyed

What does granulation tissue consist of?

Proliferating fibroblasts laying down immature connective tissue (type III collagen) Proliferating new blood vessels

What is Organization in the context of tissue repair, and what are some features?

Process of transforming granulation tissue into a dense scar blood vessels become less prominent and collagen matures (type III collagen replaced by type I collagen)

What do macrophages do in the process of skin healing?

Remove debris, secrete cytokines

What do fibroblasts do in the process of skin healing?

produce extracellular connective tissue matrix

What do myofibroblasts do in the process of skin healing?

contract the wound - modified fibroblasts with functional features of contractile smooth muscle cells

What is fibrosis?

the excess deposition of collagen and other ECM proteins in a tissue

What is the function of Vit C in wound healing?

Cofactor for hydroxylation reactions (cross-linking of lysine and proline in collagen synthesis)

How does a deficiency in Vit C alter affect wound healing?

Scurvy Impaired wound healing Blood vessel fragility

What is the basis of a Vit C deficiency?

Diets lacking fruits and vegetables

What is the function of Zinc in wound healing?

Cofactor for metalloenzymes (Collagenase)

How does a deficiency in Zinc alter affect wound healing?

Poor wound healing Growth impairment

What is the basis of a Zinc deficiency?

inadequate intake, alcoholism, chronic diarrhea, and inflammatory disease

What is the function of Copper in wound healing?

Cofactor for lysyl oxidase – cross links lysine and hydroxylysine

How does a deficiency in Copper alter affect wound healing?

Abnormal collagen cross-linking, poor wound healing Muscle weakness Neurologic deficits

What is the basis of a Copper deficiency?

Usually due to total parenteral nutrition

What is contracture?

stiffness/constriction of muscles/joins restricting normal movement

What is dehiscence?

Opening of healing or partially healed wound with separation of its edge

What can cause dehiscence?

mechanical factors infection ischemic necrosis of sutured edges

Summary

Regeneration can occur in organs and tissues composed of mitotically labile and stable cells Organs composed of postmitotic (permanent) cells cannot regenerate Wound healing is the best example of repair in which the granulation tissue plays a key role Crucial components of wound healing are the cells, such as fibroblasts, macrophages, and their products, including ECM proteins.