1 / 29

Mechanisms of Tissue Regeneration and Fibrous Repair | Pathology Insights

Explore the intricate processes of regeneration and fibrous repair in tissues, including factors influencing these mechanisms and complications that may arise. Delve into the specific features of healing in various organs.

eddiem
Download Presentation

Mechanisms of Tissue Regeneration and Fibrous Repair | Pathology Insights

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Leicester Warwick Medical School Mechanisms of Disease Regeneration andFibrous Repair Dr Peter Furness pnf1@le.ac.uk Department of Pathology

  2. REGENERATION AND REPAIR • Regeneration: replacement of functional, differentiated cells • Repair: production of a fibrous scar

  3. REGENERATION • Labile cells: - normal state is active cell division - usually rapid regeneration • Stable cells: - not normally dividing at a significant rate - speed of regeneration variable • Permanent cells: - unable to divide - unable to regenerate

  4. Factors controlling regeneration: Complex and poorly understood. • ‘Growth factors’ • EGF, PDGF, FGF, IGF ... • Hormones e.g. ACTH, œstrogen, growth hormone... • Contact with basement membranes & adjacent cells • Signalling through integrins • NOTE: importance of growth control in CANCER.

  5. Mitotic figures Acute damage to kidney - regeneration

  6. FIBROUS REPAIR: The development of a fibrous scar. • Rabbit ear chamber example. • Blood clot forms. • Acute inflammation around the edges. • Chronic inflammation: Macrophages infiltrate the clot. • Capillaries and lymphatics sprout and infiltrate. • Myofibroblasts infiltrate and differentiate. • Glycoproteins and COLLAGEN are produced • Cell population falls, vessels differentiate and are reduced in number. • Collagen matures AND CONTRACTS.

  7. Rabbit Ear Chamber: Direct observation of fibrous repair. 1) Exudate clots. 2) Neutrophils infiltrate and digest clot 3) Macrophages and lymphocytes are recruited

  8. Rabbit Ear Chamber: Direct observation of fibrous repair. 4) Vessels sprout, myofibroblasts make glycoproteins 5) Vascular network; collagen synthesised; macrophages reduced 6) Maturity. Cells much reduced; collagen matures, contracts, remodels

  9. Angiogenesis

  10. The Extracellular Matrix • Collagen • Type I - Bone, tendon, scars. Type III - ‘tissue scaffold’. Type IV - non-fibrous, basement membranes ... • Elastin • Glycoproteins • Fibronectin, Osteonectin, Tenascin,... • Proteoglycans • Heparan sulphate proteoglycan, ...

  11. Specific features of fibrous collagens • Triple helical fibrils • Fibrils arrange in ‘quarter stagger’ mode to form insoluble fibres • Relatively resistant to general proteases; slow remodelling by specific collagenases

  12. SKIN WOUNDS:Healing by “Primary Intention” • Epidermis regenerates • Dermis undergoes fibrous repair. • Sutures out at 5-10 days: approx. 10% normal strength. • Maturation of scar continues up to 2 years. • Minimal scarring, good strength • Risk of trapping infection under skin - produces abscess.

  13. Healing by ‘primary intention’: A clean, sutured wound.

  14. SKIN WOUNDS:Healing by “Secondary Intention” • Quantitative differences. • Initial contraction (in furry animals!) • Clot dries to form a ‘scab’ or ESCHAR • Epidermis regenerates beneath. • Repair process produces GRANULATION TISSUE • Comparison with primary intention: • Takes longer • Produces a larger scar; not necessarily weaker • Produces more late contraction

  15. An open wound: Healing by ‘secondary intention’

  16. Regeneration and repair combined:A chronic peptic ulcer

  17. Regeneration and repair combined:A chronic peptic ulcer

  18. CONTROL OF REPAIR Poorly understood. • Angiogenesis • Various angiogenic cytokines, e.g. VEGF, bFGF ... • Fibrosis • various pro-fibrotic cytokines, e.g. TGF beta, PDGF, ... • Limitation of fibrosis and remodelling • Hardly anything known!

  19. FACTORS INFLUENCING WOUND HEALING • Local factors: • Type, size, location of wound • Apposition, lack of movement • Infection: Suppuration, Gangrene, Tetanus • (Secondary hæmorrhage) • Blood supply: Arterial, Venous • Foreign material: dirt, glass, sutures, necrotic tissue • Radiation damage

  20. FACTORS INFLUENCING WOUND HEALING • General Factors: • Age • General state of health • chronic diseases e.g. diabetes, rheumatoid arthritis etc. • Drugs (n.b. steroids) and hormones • General cardiovascular status • General dietary deficiencies e.g. protein • Specific dietary deficiencies • Vitamin C • sulphur-containing amino acids

  21. Complications of Repair • Insufficient fibrosis: • Wound dehiscence; hernia; ulceration • Excessive fibrosis: • Cosmetic scarring; hypertrophic scars; keloid • Excessive contraction: • Limitation of joint movement (Contractures); obstruction of tubes & channels (Strictures)

  22. Coal worker’s pneumoconiosis

  23. Alcoholic cirrhosis in the liver

  24. Special features of healing in specific organs For self-directed study. As a minimum, learn about: • Liver (n.b. regeneration in acute versus chronic damage) • Kidney (n.b. ‘acute tubular necrosis’) • Heart (see ‘myocardial infarction’) • Bone (n.b. ‘Callus’) • Cartilage (Can it???) • Peripheral nerve (n.b. ‘Wallerian degeneration’; axon sprouting) • Central nervous system (n.b. gliosis)

  25. ‘Contracture’following a major burn

More Related