This action might not be possible to undo. Are you sure you want to continue?
• The body ability to replace injured or dead cells and to repair tissues after inflammation is critical to survival • The repair of tissue damage can be broadly seperated into two processes: regeneration and healing
such as the growth of an amputated limb in amphibian • In mammals: this term is used in processed applied to liver (partial hepatectomy) and kidney (unilateral nephrectomy) not really true regeneration • The continuous regeneration applied to epithelial tissue of skin and GI tract TUMS300309 . REGENERATION • Refers to growth of cells and tissues to replace lost structures.Definition……. There are two important distinctions included in repair: regeneration and healing.
Definition……. A wound (commonly in the skin) 2. Inflammatory process in internal organs 3. is usually a tissue response to: 1. Cell necrosis in organs incapable of regeneration In this broad definition may include: • Atherosclerosis: a condition considered to be an attempt to heal injury of the arterial wall Healing consists of variable proportions of two distinct processes: regeneration and laying down of fibrous tissue (scar formation) TUMS300309 . HEALING.
REPAIR resume Two distinct processes: Regeneration Replacement of injured cells by cells of the same type Fibroplasia / fibrosis Replacement of injured cells by connective tissue cell migration cell proliferation & differentiation cell-matrix interaction (ECM organization & remodelling) Repair (proses dasar) TUMS300309 .
Mechanism regulating cell populations Cell Differentiation TUMS300309 .
Cell Differentiation TUMS300309 .
Control of Normal Cell Growth Normal Cell Injury Cell death Mechanical deformation of tissue Proliferation Microenvironment TUMS300309 Cell replication .
2. TUMS300309 . 3.Cell Cycle Landmark 1.
kidney.Parenchymal cells: liver.Mesenchymal cells: fibroblast. cervix . vagina. salivary glands.Transitional epithelium of urinary tract . skeletal muscle. smooth muscle .Neurons.Vascular endothelial cells Nondividing / permanent cells . pancreas .Surface epithelia of the skin.Cells of the bone marrow and hematopoietic tissue Quiescent / stable cells (low level replication) . oral cavity.The lining mucosa of the excretory ducts of glands: pancreas. billiary tract .Cell-groups based on the proliferative capacity Continuously dividing cells (labile cells) .Columnar epithelium of the gastrointestinal tract and uterus . heart muscle TUMS300309 .
JAK/STAT pathway TUMS300309 .Receptors without intrinsic tyrosine kinase activity .IP3 pathway . paracrine.Molecular Events in Cell Growth Cell Signaling (autocrine.Receptors with intrinsic tyrosine kinase activity .cAMP pathway .MAP-kinase pathway .PI-3 kinase pathway . endocrine) Cell Surface Receptors .G Protein-Linked Receptors Signal Transduction System .
General Patterns of Intracellular Signaling TUMS300309 .
Cell surface receptors and principal signal transduction pathways TUMS300309 .
TNF VEGF. TGF-β. EGF. IL-1 PDGF. Ang. FGF. TGF-β PDGF. TNF. TGF-β inhibits TUMS300309 . FGF. FGF.TNF. FGF TGF-β. FGF. EGF. PDGF PDGF.Growth Factors and Cytokines Affecting Various Steps in Wound Healing Monocyte chemotaxis Fibroblast migration Fibroblast proliferation Angiogenesis Collagen synthesis Collagenase secretion PDGF. EGF.
The inflammatory reaction contains : • The damage • Eliminates the damaging stimulus • Remove injured tissue • Initiates the deposition of ECM components in the area of injury TUMS300309 .REPAIR The goal of the repair process is to restore the tissue to its original state.
Migrasi sel selama repair 1. Perisit lepas masuk ke matrix 4. Epitel keratinosit lepas dari kelompoknya. menembus membran basal. Fibroblas menjadi bipolar dan migrasi menembus matrix menuju ke tempat lesi 5. migrasi di antara luka sepanjang matrix dermis Migrasi sel memicu repair TUMS300309 . Lekosit keluar dari vasa darah. migrasi ke dalam matrix untuk membentuk kapiler baru 3. Endotel lepas dari membran basal. masuk ke matrix 2.
Scar Formation and Fibrosis • Induction of an acute inflammatory process by the initial injury • Regeneration of parenchymal cells • Migration and proliferation of both parenchymal and connective tissue cells • Synthesis of ECM proteins • Remodeling of connective tissue and parenchymal components • Collagenization and acquisition of wound strength TUMS300309 .a complex but orderly phenomenon involving a number of processes Repair by Healing.
Hal 113 TUMS300309 .
edema and a loose ECM containing inflammatory cells.Granulation tissue & mature scar Numerous blood vessels. TUMS300309 Dense collagen and scattered vascular channels collagen .
ANGIOGENESIS TUMS300309 .
Angiogenesis capillary sprouting TUMS300309 .
Tissue Remodeling: MMP regulation TUMS300309 .
Orderly Phases of Wound Healing TUMS300309 .
Regulation of vascular morphogenesis by receptor tyrosine kinases and their ligands TUMS300309 .
Wound Healing TUMS300309 .
Extensive redundancy is present. 2-4 days (thrombus) GF controlling migration of cells are illustrated.Cutaneous wound. Most factors has multiple effects. . and no TUMS300309 growth factor is rate limiting.
TUMS300309 . 4-8 days (thrombus) Blood vessels are proliferating.Cutaneous wound. but not at its surface. and the epidermis is penetrating the thrombus. The upper portion will become an eschar or scab.
The binding of fibronectin to cell membranes. 3. Macrophages recruited to the wound area. Fibronectin. cell debris. collagen. process cell remnants. A fibrin clot forms and fill the wound gap.Summary of healing process 1. and bacterial products are chemoattractants for a variety of cells that recruited to the wound site (2-4) TUMS300309 . and bacteria (opsonization) facilitates phagocytosis by these macrophages and contributes to the removal of debris (1-3 days). DNA. Fibronectin in the extravasated plasma is cross-linked to fibrin. proteoglycans. and other ECM component by the action of transglutaminases provides a provisional mechanical stabilization of the wound (0-4 hours) 2. collagens. and damaged ECM.
Summary of healing process 4. As a new ECM is deposited at the wound site. Eventualoly temporary matrix is removed by a combination of extracellular and intracellular digestion. is deposited (5 days-weeks) TUMS300309 . Final phase of the repair reaction. Concurrent with fibrin removal. the initial fibrin clot is lysed by a combination of extracellular proteolytic enzymes and phagocytosis (2-4 days) 5. and the definitive matrix. and type III collagens (2-5 days) 6. glycoprotein. rich in type one collagen. there is deposition of temporary matrix formed by proteoglycan.
Systemic factors influence healing
• Nutrition (deficiency vitamine C) • Metabolic status (DM) • Circulatory status • Hormones (glucocorticoid inhibit collagen synthesis)
Local factors influence healing
• Infection • Mechanical factors • Foreign bodies • Size: location, and type of wound
exuberant granulation granuloma .hypertrophic scar .Pathologic Aspects of Wound Repair • Deficient scar formation .ulceration • Excessive formation of the repair components .wound dehiscence .desmoid (aggressive fibromatosis • Formation of contractures deformities of the wound and surrounding tissue TUMS300309 .
Healing of skin ulcers Pressure ulcer of the skin. commonly found in diabetic patient Skin ulcer with large gap between the edges of the lesion TUMS300309 .
Healing of skin ulcers A thin layer of epidermal epithelization and extensive tissue granulation formation in the dermis TUMS300309 Continuing reepithelization of the epidermis and woud contraction .
TUMS300309 .Healing of skin ulcers KELOID Excess collagen deposition in skin forming a raised scar known as keloid.
INJURY VASCULAR & CELLULAR RESPONSE ACUTE INFLAMMATORY EXUDATION Stimulus promptly destroyed No/minimal necrosis of cells Exudate resolved Exudate organized Stimulus not promptly destroyed Tissue of stable or labile cells Framework intact Framework destroyed Necrosis of cells Tissue of permanent cells Restitution of normal structure Mild heat injury Scarring Fibrinopurulent .pericarditis .peritonitis Regeneration Restitution of normal structure Lobar pneumonia Scarring Bacterial abscess Scarring Myocardial infarction TUMS300309 .
Nerve damage. Tearing of tendineous insertions & ligamentous attachment 4.FRACTURE • The most common bone lesion • Fracture is defined as a discontinuity of bone • A force powerful enough to fracture a bone may also injures the adjacent soft tissue results in: 1. Extensive muscle necrosis 2. caused by stretching or direct tearing of the nerve TUMS300309 . Hemorrhage (shearing of capillary beds and larger vessels of soft tissue) 3.
FRACTURE • Traumatic and non traumatic fracture • Complete and incomplete fracture (greenstick) • Closed (simple) fracture • Compound fracture • Comminuted fracture • Pathologic fracture • Stress fracture TUMS300309 .
medullary cavity. FGF. TGF-β. provides fibrin mesh) simultaneously degranulated pletelets and migrating inflammatory cells release PDGF.FRACTURE: mechanism of healing process rupture of blood vessels hematoma (fills the fracture gap & surrounds the area of bone injury. and ILs activate the osteoprogenitor cells in the periosteum. and surrounding soft tissue stimulate the production of osteoclastic and osteoblastic activity……… TUMS300309 .
FRACTURE: mechanism of healing process TUMS300309 .
Bone Matrix Active osteoblast synthesizing bone matrix. The surrounding spindle cells represent osteoprogenitor cells. TUMS300309 .
Two osteoclasts resorbing bone TUMS300309 .
Paracrine molecular mechanisms that regulate osteoclasts formation and function. TUMS300309 .
FRACTURE……….. By the end of the first week: • The hematoma is organized • The adjecent tissue is being modulated for future matrix production • The fractured ends of the bones are being remodeled Soft tissue callus / procallus provides some anchorage between the ends of the fractured bones (No structural rigidity for weight bearing) TUMS300309 .
FRACTURE: mechanism of healing process TUMS300309 .
FRACTURE: next step Activated osteoprogenitor cells deposit woven bone in the subperiosteal trabeculae. perpendicularly to cortical axis and within the medullary cavity Activated mesenchymal tissue cells differentiate into chondroblast fibrocartilage and hyaline cartilage enveloping the fracture site Woven bone approaches the newly formed cartilage at the fracture line enchondral ossification the fracture ends are bridged by a bony callus TUMS300309 .
Fracture Callus TUMS300309 Osteoid tissue Bony callus .
Woven bone deposited on the surface of preexisting lamellar bone TUMS300309 .
FRACTURE The healing of a fracture is divided into 3 phases: 1. The reparative phase 3. The remodeling phase TUMS300309 . The inflammatory phase 2.
FASA RADANG • 1-2 hari sesudah fraktur ruptur vasa darah pada perios. otot. dan jaringan lunak hemoragi hebat • Nekrosis luas pada tulang daerah fraktur hallmark untuk tulang mati: tidak ada osteosit dan lakuna osteosit kosong • 2-5 hari hemoragi bekuan darah resorbsi.I. neovaskularisasi dari tepi jendalan darah dalam 7 hari jendalan diorganisasi oleh invasi vasa darah dan fibrosis TUMS300309 .
I. sel mesenkimal pluropotensial (dari jaringan lunak dan sumsum tulang) osteoblas membentuk woven bone dan kartilago osifikasi enkondral kalus (jaringan granulasi berisi tulang dan kartilago) TUMS300309 . FASA RADANG • Sesudah 7 hari mulai terbentuk “woven bone” dimulai dari tepi jendalan.
II. FASA REPARATIF • Mulai minggu ke 2 sampai berbulan kemudian (tergantung pada derajat gerakan dan fiksasi fraktur) pada saat ini sel-sel radang tidak ditemukan lagi • Proses reparasi melibatkan diferensiasi sel-sel pluripotensial menjadi fibroblas dan osteoblas TUMS300309 .
FASA REPARATIF Reparasi mula dari tepi ke tengah fraktur untuk menyelesaikan proses: 1. yang akan menjembatani daerah fraktur TUMS300309 . Mengorganisasi dan meresorbsi jendalan darah 2. Menyediakan neovaskularisasi untuk membentuk kalus.II.
FASA REMODELING • Basic multicellular unit (BMU): kerja sama osteroklas dan osteoblas proses pembentkan dan resorpsi homeostasis masa tulang • Tulang tumbuh dan membesar modeling maturitas penghancuran dan pembaharuan remodeling • Pada orang dewasa ada 1jt BMU yang aktif remodeling 10 % skeleton/th TUMS300309 .III.
TUMS300309 .Bone remodeling seqence Initiated by the appearance of osteoclasts on a bone surface previously lined by fusiform cells After development of a resorption bay. osteoclast are replaced by osteoblast Deposit new bone The bone loss that attend aging (senile osteoporosis) is due to incomplete filling of resorption bays.
RESUME • Migration of cells initiate repair • • • • ECM sustains the repair process ECM components are elaborated and modified in repair Remodeling is the long-lasting phase of repair Cell proliferation is evoked by cytokines & matrix • • • • Integrated molecular signals mediate proliferation and differentiation Three protein family transduce signals to the nucleus Outcomes of injury include repair and regeneration Wound healing exhibit a defined sequence • • • • The cell cycle leads to mitosis Cells can be classified by their proliferative potential Regeneration is mediated by either stem cells or stable cells Local factors may retard healing • • Specific sites exhibit different repair pattern Wound repair is often suboptimal TUMS300309 .
The basic Process of wound healing • Migration of cells initiate repair • ECM sustains the repair process • ECM components are elaborated and modified in repair • Remodeling is the long-lasting phase of repair • Cell proliferation is evoked by cytokines & matrix • Integrated molecular signals mediate proliferation and differentiation • Three protein family transduce signals to the nucleus TUMS300309 .
Repair • Outcomes of injury include repair and regeneration • Wound healing exhibit a defined sequence TUMS300309 .
Regeneration • The cell cycle leads to mitosis • Cells can be classified by their proliferative potential • Regeneration is mediated by either stem cells or stable cells TUMS300309 .
Conditions that modify repair • Local factors may retard healing • Specific sites exhibit different repair pattern • Wound repair is often suboptimal TUMS300309 .
C. mitogenik terhadap sel endotelial TUMS300309 .Vascular Endothelial Growth Factor (isoform A.D) (VEGF) Sumber Sel menkimal Fungsi Meningkatkan permeabilitas vaskular.B.
D) (EGF) Sumber Platelet. fibroblas. makrofag. sel otot polos. dan otot polos TUMS300309 . Fungsi Kemotaktik untuk pmn.C.Platelet Derived Growth Factor (isoform A.B. endotel. keratinosit. makrofag.
limfosit T. hepatosit. dan motilitas sel TUMS300309 . jaringan lain Fungsi Meningkatkan proliferasi selsel epitelial dan endotelial. keratinosit.Transforming Growth Factor Alpha (TGF-α) Sumber Makrofag.
This action might not be possible to undo. Are you sure you want to continue?
We've moved you to where you read on your other device.
Get the full title to continue listening from where you left off, or restart the preview.