Repair: Tissue Regeneration and Fibrosis

‫بسم هللا الرحمن الرحيم‬  REPAIR By Dr. Noha Abd El Rahim Ass. Prof of Pathology ILOs:  Define repair and its types  Mention the factors that affect wound healing and why this system of repair can fail.  Define the term regeneration and give examples of repair b...

‫بسم هللا الرحمن الرحيم‬  REPAIR By Dr. Noha Abd El Rahim Ass. Prof of Pathology ILOs:  Define repair and its types  Mention the factors that affect wound healing and why this system of repair can fail.  Define the term regeneration and give examples of repair by regeneration.  Enumerate pathological processes where repair occurs by fibrosis and mention the phases of repair.  Describe the phases of healing of a surgical wound and that of a gaping wounds and mention complications ofwound healing  Desribe the process of healing of bone fractures Definition - Repair is the process by which damaged and necrotic tissues are replaced by a new healthy one. - It begins early in inflammation Types of cells according to the power of regeneration 1- Labile cells 2- Stable cells 3- Permanent cells 1- Labile cells: These cells proliferate continuously throughout life to replace aging cells e.g. stratified squamous epithelium of the skin, respiratory epithelium, GIT epithelium and haemopoietic & lymphoid tissue.  2- Stable cells: - Do not proliferate under normal conditions, but proliferate when there is need: e.g. *Parenchymatous stable cells as liver, pancreas and endocrine glands *Mesenchymal stable cells as fibroblasts, chodroblasts and osteoblasts. - Small damage of stable cells: regeneration - Large damage of stable cells: repair with fibrosis 3- Permanent cells: Cannot proliferate at all, it includes: *Muscle cells: damaged muscle cells are replaced by fibrous tissue deposited by fibroblasts (fibrosis) e.g. cardiac and skeletal muscles *Nerve cells: damaged nerve cells are replaced by glial cells deposited by astrocytes (gliosis) Labile cells Permenant cells Stable cells Types and mechanisms of repair Repair by regeneration Repair by fibrosis Healing by regeneration - Replacement of the damaged cells by new healthy cells of the same type - It occurs due to multiplication of the surviving cells. - This is frequently seen in repair of GIT mucosa, liver, bones and epidermis (i.e. tissues composed of labile or stable cells)  Healing by fibrosis (organization) - Repair of damaged tissue takes place by granulation tissue which is formed of fibroblasts, collagen, and newly formed capillaries. -The granulation tissue is later on replaced by fibrous tissue which is called scar. -This mechanism of repair occurs in tissues with permanent cells as those of C.N.S (Gliosis), cardiac and skeletal muscles.  Granulation Tissue 220px-Finger_with_granulation_tissue Pink granular tissue highly resistant to infection bleed on touch insensitive to touch Formed of proliferating capillaries and fibroblasts 250px-Scar_%28xndr%29 Mechanisms of granulation tissue formation 1- Angiogenesis (Neovascularization)  Under the effect of VEGF  Migration from nearby healthy vessels  Form solid buds then canalize to form capillary loop Fibrogensis  Synthesis of collagen  Migration and proliferation of fibroblasts  Under the effect of growth factors (FGF, EGF, PDGF)  They fill and bridge the wound and lay down collagen (Type III then Type I)  And extracellular matrix protein as fibronectin Fibrous tissue formation Fibroblasts secretes protocollagen molecules condensation Reticular fibers condensation Collagen fibers compressing the capillaries with obliteration Diminished vascularity Change of fibroblasts into fibrocytes Mature fibrous tissue (scar)  Dense collagen fibers (Type I) and fibrocytes with few or no capillaries.  In old scar there is contraction by special types of fibroblasts (myofibroblasts)  Type III (thin fibers), type I (broad)  Factors affecting repair Local factors 1- Severity and extent of tissue damage: A cut wound with minimal tissue damage heals within few days, while lacerated wound with considerable tissue loss takes a longer period for repair 2- Types of damaged cells: Labile cells (as surface epithelium) possess a rapid rate of regeneration than stable cells (as those of bone and cartilage). 3- Arterial blood supply: It should be sufficient to supply the area by nutrients and oxygen, required for division of cells. 4- Presence or absence of bacterial infection: Healing of clear surgical incisions occurs within few days, whereas infected dirty wounds and severe inflammatory lesions, as large abscess, show a delayed repair, which may extend for weeks or months. 5- Presence of foreign body: Delay the process of repair.  General factors 1- Age of the patient: Tissues of infants and children have a higher rate of repair than those of adults. 2-Vitamin deficiency: (especially vit. C,A,D) - Vit C is essential for synthesis of ground substances of connective tissue and osteoid of bone, - Vit A for a healthy epithelium, - Vit D for bone formation.  3- Protein deficiency Especially amino acids 4- Diabetes mellitus: Diabetic patients has delayed healing of wounds 5- Hormones Glucocorticoids delays healing while growth hormone and anabolic steroids increase healing 6- Immobilization is very important in healing of bone fractures  Healing of wounds  Primary union of wounds (healing by first intention)  Secondary union of wounds (healing by secondary intention)  Primary union of wounds (healing by first intention) Occur in clean incised wounds With minimal tissue destruction Edges are approximated e.g. by sutures e.g. surgical wounds Mechanism: 1- Blood clots between wound edges and on the surface 2-The basal cell layer of the epidermis on both edges of the wound proliferate across the clot to meet in the center and then divides to fill the whole thickness of the epidermis. 3- The gap of the wounds under the new epithelium gets filled by granulation tissue 4- Maturation of granulation tissue into a thin avascular fibrous tissue band uniting the edges of the wound called scar.  Secondary union of wounds (healing by secondary intention Occurs in gapping septic wounds or abscesses 1- The gap of the wound is filled by blood clots, necrotic debris or pus. 2- The epidermal cells at the margins proliferate across the blood clots. They do not cover the wound until the gap gets filled by granulation tissue up to the level of the basal layer of the epidermis. 2- The gap gets filled from below upwards and from the sides by granulation tissue. 3- the basal cell layer around the cavity proliferates to cover the granulation tissue and divides to form the whole epidermal thickness 4- the granulation tissue mature to fibrous tissue. The wound contract by the action of myofibroblasts  Primary Secondary union Union - Type of wound Incised septic - Tissue destruction minimal marked - Secondary infection absent present - Edges approximated gaped - Rate of healing Rapid slow - Amount of Small Large granulation tissue - Scar size Small Large - Complications Rare More common Complications of wound healing 1- chronic ulcer: persistent loss of continuity of the surface epithelium 2- Sinus: a blind ended tract between the depth of the wound cavity and the skin surface 3- Fistula: A tract between the abscess cavity and a hollow organ or between two hollow organs  17bb 4- keloid: large ugly scar projecting on the surface and covered by stretched epidermis due to overdone repair. 6- Infection: lead to delayed healing 7- Contracture: in scar on flexure and may interfere with Movement 7- Weak scar: lead to surgical hernia 8- Dehiscence: opening of healing wound 9- Implantation (epidermoid) cyst 10- Malignant transformation (squamous cell carcinoma)  Healing of bone fracture For union to occur the two fracture ends must be fixed together Bleeding and hematoma formation because some vessels of bone and soft tissue are torn on Mild inflammatory reaction and accumulation of inflammatory fluid exudates due to mechanical trauma Phagocytosis of necrotic debris by macrophages  Granulation tissue invasion of the hematoma New osteiod tissue is formed by osteoblasts A wellformed callus is divided into: External callus (subperiosteal), intermediate callus (between the fracture ends), and internal callus (in medullary cavity) Osteoclasts remove both internal and external calli leaving the intermediate one which form the permanent callus. Remodling of the permanent callus by osteoclastic and osteoblastic activity continue with formation of lamellar bone uniting the fracture ends with reopening of the medullary cavity and regeneration of bone marrow Factors leads to failure of bone union: 1) Infection 2) Pathological fracture 3) Poor opposition 4) Mobilization 5) Poor blood supply 6) Deficiency of protein, calcium or vitamins 7) Old age Complications of bone healing  Delayed union: ischeamia, poor blood supply, deficiency of proteins and vitamins C&D, infection (compound fracture), improper immobilization  Malunion: improper immobilization  Fibrous union (Pseudoarthritis)  Non union: due to soft tissue interposition between the two broken ends of the bone.  Repair in nervous system 1) Central nervous system: No regeneration of brain or spinal cord. The dead cells are removed by microglia and replaced by neuroglial cells in a process called (Gliosis) 2) Peripheral nerves: Regeneration may occur; two types of degeneration affect peripheral nerves: a) Axonal degeneration: affect nerve cell b) Wallerian degeneration: affect distal fragment and proximal fragment of nerve fiber Schwann cells proliferate on both sides to form tube in which new myelin and axis cylinder grow at a rate of 1 mm/ day Thank You