Growth and repair
1 / 40

Growth and Repair - PowerPoint PPT Presentation

  • Uploaded on

Growth and Repair. dr. FAIRUZ QUZWAIN,SpPA,M.Kes Kepala bagian Patologi Anatomi FKIK-UNJA. Repair following inflammation: two simultaneous processes. Regeneration : replacement of injured/necrotic cells by cells of same type, often leaving no evidence of previous injury

I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
Download Presentation

PowerPoint Slideshow about 'Growth and Repair' - ohanzee-ojeda

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.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.

- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Growth and repair

Growth and Repair


Kepala bagian Patologi Anatomi


Repair following inflammation two simultaneous processes
Repair following inflammation: two simultaneous processes

  • Regeneration : replacement of injured/necrotic cells by cells of same type, often leaving no evidence of previous injury

  • Repair : replacement of injured/necrotic cells by connective tissue, leaving a permanent scar (microscopic or macroscopic)

Cell cycle
Cell Cycle

PHASES of Cell Cycle:






Correlation of cell cycle and tissue types
Correlation of Cell Cycle and Tissue Types

  • Continuously dividing (labile) cells:

    • Surface epithelium and excretory ducts of glands (skin, gi / gu mucosa, biliary tract, pancreas)

    • Marrow hematopoietic cells

    • Stem cells in multiple organs (immature, undifferentiated cells)

  • Quiescent (stable) cells in G0:

    • Organ parenchymal cells (liver, kidneys)

    • Mesenchymal cells (fibroblasts, smooth muscle, endothelium, chondrocytes, osteocytes)

  • Nondividing permanent cells (can’t re-enter cell cycle)

    • Neurons, skeletal & cardiac myocytes

Mechanism control of cell cycle
Mechanism: control of cell cycle

Which cyclin ?

Which cyclin?

Cyclin-dependent kinase inhibitors

Modes of intercellular signalling
Modes of Intercellular Signalling




Surface receptors 3 classes
Surface Receptors: 3 classes

Receptors without intrinsic tyrosine kinase

Receptors with intrinsic tyrosine kinase

Seven transmembrane (G protein-coupled)

Consequences of receptor activation
Consequences of Receptor Activation

  • Intrinsic-kinase activity receptors:

    • Irreversible commitment of cell to enter

      (proliferative response)

  • Receptors without intrinsic kinase activity (cytokine superfamily):

    • Activation cytosolic kinases to mediate functional response (not proliferative)

  • G-protein coupled (seven spanning) receptors:

    • Over 1500 receptors identified

    • Bind various ligands, producing specific intracellular response

Signal transduction by tyrosine kinase receptors
Signal Transduction by Tyrosine Kinase Receptors

Growth factors: coming soon!

Clinical application: if mutant ras protein is permanently fixed in active GTP form, what pathologic process may result?

Transcription factors
Transcription Factors

  • Definition: intracellular proteins that regulate gene expression, thereby controlling cell growth

  • Specific domains in transcription factors:

    • : permits factor to bind specifically to short

      sequences of DNA

    • : allows factor to increase transcription of DNA

    • :allows factor to decrease transcription of DNA

  • Transcription factors known to be operative in malignant neoplasms:

    • Growth promoting: c-MYC and c-JUN

    • Cell cycle inhibiting (tumor suppressor gene): p53

Growth factors
Growth Factors

  • Definition: proteins that bind to cell surface receptors with generating cascade response that signals cell to enter S-phase (cell division).

  • These factors can also modulate cell functions: locomotion, contractility, differentiation, etc.

Major growth factors effects
Major growth factors / effects


  • Mitogenic for epithelium & fibroblasts

  • Mitogenic for hepatocytes

     Mitogenic for endothelial cells

  • Mitogenic for monocytes, fibroblasts, smooth muscle cells; activates neutrophils

  • Angiogenesis, wound repair (mitogenic for both fibroblasts and keratinocytes)


  • EGF = epidermal

  • TGF-a = transforming

  • VEGF=vascular endothelial

  • PDGF= platelet-derived

  • FGF= fibroblast

  • FGF-1=acidic

  • FGF-2=basic

Tissue regeneration
Tissue Regeneration

Liver from living donor before transplantation, outlining right lobe to be used for grafting into recipient

Liver of donor one week post-partial hepatectomy, showing marked growth of left lobe (compensatory hyperplasia) without regrowth of right lobe. Why didn’t right lobe regrow also?

Extracellular matrix 1
Extracellular matrix 1

  • Definition: macromolecules outside cells, formed by local secretion and assembled into network surrounding cells

  • Functions:

    • Sequester H2O for turgor; minerals for rigidity

    • Reservoir for growth factors

    • Scaffolding within which cells adhere, migrate, and proliferate

Extracellular matrix ecm 2
Extracellular matrix (ECM) 2

  • Groups of macromolecules in ECM:

    • Fibrous structural proteins: 2 major families are:

    • Adhesive glycoproteins

    • Gel proteins in intercellular junctions and cell surfaces: proteoglycans & hyaluronic acid

Extracellular matrix ecm 3
Extracellular matrix (ECM) 3

  • Macromolecules of ECM assemble into two types of organizational structure:

    • : fills spaces between cells

    • : closely associated with cell surfaces

Collagen summary of major types
Collagen: summary of major types

Skin (80%), bone (90%), tendons

Genetic deficiency of type IV in:

Collagen synthesis
Collagen synthesis

Nutrient required for hydroxylation of alpha chains:

Deficiency of this nutrient causes poor wound healing in disease called:

Inherited disorders of collagen synthesis, leading to defective fibers:

Elastic fibers
Elastic Fibers

  • Definition: fibers capable of stretching and recoiling to original size

  • Present in tissues requiring elasticity:

  • Structure:

    • Central core protein:

    • Peripheral microfibrillary network:

    • Inherited defect synthesis of peripheral microfibrillary network: abnormally weakened elastic fibers. Syndrome?

Skin, lung, uterus, ligaments, large blood vessels

Adhesion molecules 1
Adhesion molecules 1

Function: attach cells to ECM matrices; 2 glycoprotein chains held together by disulfide bonds; produced by fibroblasts, endothelial cells, & monocytes. Name?

Adhesion molecules 2
Adhesion molecules 2

Most abundant glycoprotein in basement membranes; it spans basal lamina and binds to both cell surfaces and ECM components:

Adhesion molecules 3
Adhesion molecules 3

Transmembrane glycoproteins with alpha and beta chains that bind to fibronectin, laminin, & collagen. This family of surface receptors mediate attachment of cell membranes to ECM:

These also mediate adhesion of which cell type to endothelium?

Summary interactions cell ecm
Summary: interactions cell-ECM

Major EC structural protein:

Fig. 3-16, Pathologic Basis of Disease, 7th ed, Elsevier 2005

Overview repair after injury
Overview: Repair after injury


Damage to parenchymal cells and interstitial framework

Regeneration of parenchymal cells whenever possible

Replacement of non-regenerated damaged tissue by what?

Fibrosis fibroplasia
Fibrosis (fibroplasia)

  • Four components:

    • : formation new blood vessels

    • of fibroblasts into damaged tissue

    • of extracellular matrix

    • Organization fibrous tissue =

Sequence of events in repair
Sequence of events in repair

24 hrs: proliferation of fibroblasts & endothelial cells

Within 3-5 days:

Permanent result (weeks later)

Little mature collagen

Proliferation of young fibroblasts

blue-staining collagen (trichrome stain)

New capillaries


  • Definition: pre-existing vessels send out capillary sprouts to form new vessels

  • cf. vasculogenesis: the primitive vascular network established during embryogenesis

  • Clinical importance:

    • Repair post-inflammation

    • Formation collateral circulation (post-MI)

    • Support growth of neoplasms (therapeutic implications)

Ecm proteins affecting angiogenesis
ECM proteins affecting angiogenesis

  • Integrins: formation and maintenance new vv.

  • Matrix proteins which destabilize cell-matrix interactions, promoting angiogenesis:

    • Thrombospondin

    • SPARC

    • Tenascin C

  • Proteases that remodel matrix

    • Plasminogen activators

    • Matrix metalloproteinases

  • Fragment of collagen that inhibits endothelial proliferation and angiogenesis, with therapeutic application in neoplasia?

Fibrosis fibroplasia1
Fibrosis (fibroplasia)

  • Emigration and proliferation of fibroblasts at injury site, triggered by multiple growth factors produced by cells in granulation tissue, most important of which is:

  • ECM deposition by fibroblasts: fibrillar collagen synthesis enhanced by growth factors and cytokines, thus converting

Into a

Tissue remodeling
Tissue remodeling

  • Conversion granulation tissue into scar involves changes in composition of ECM.

  • : enzymes which degrade ECM components for remodeling. These enzymes are dependent on ions for activity.

Wound healing
Wound Healing

Healing by first intention

Healing by second intention

Summary phases of wound healing
Summary: phases of wound healing

Wound tensile strength: 10% of normal at 7 days; 70-80% of normal at 3 months

Factors influencing wound healing
Factors influencing wound healing

  • Local Factors

    • : most important single cause of delay

    • Mechanical: too early motion can delay

    • Foreign bodies: may impede or cause abscess

    • Location: speed of healing proportional to richness of blood supply:

      face > trunk > extremities

    • Type of wound: primary intention heals faster than secondary intention

Pathologic complications 2
Pathologic complications, 2

  • Excessive formation of repair components:

    • Excessive granulation tissue

    • Desmoid tumor (aggressive fibromatosis)

      • Best viewed as low grade neoplasm with stubborn tendency for recurrences


  • Physicians stand in wonder at the amazing capacity of the body to restore itself after injury, usually without loss of normal function.

  • This represents an advanced kind of engineering and self-regulated maintenance function that humbles human technology.