connective tissues and extracellular matrix 2014-9

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    Connective Tissues and Extracellular

    Matrix

    Prof. F.L. Chan

    School of Biomedical Sciences

    PFOS1(23)

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    Organ = parenchymal tissue + stromal tissuee.g Mammary gland = glandular tissue (functional part) +

    connective tissue, fat cells, blood vessels, lymphatics and

    nerves (supporting part)

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    - Epithelia are avascular (no blood vessels). Epithelial cells arefunctionally dependent on the underlying connective tissue for

    exchange of oxygen, nutrients and supply of trophic factors (e.g.

    growth factors), and removal of waste.

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    General functions of connective tissues

    The diversified functions of connective tissues depend on:Variety of cell typesTypes of extracellular fibersComponents of ground substance

    1. Support and binding of other tissues(e.g. epithelia, blood vessels and nerves)

    2. Exchange of materials (via blood

    vessels) and holding body fluids3. Protection: defending the body againstinfection (by white blood cells/leukocytes)

    4. Storage of fat as reserve and insulation(by adipose tissue)

    5. Wound healing

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    Characteristics of connective tissues

    Found throughout the body and widespread in many

    primary tissues and organs Connective tissues consist of cells and extracellularmatrix which includes extracellular fibers, groundsubstance (gel-like non-structural material) and tissue

    fluid Connective tissue comprises a very diverse group of

    tissues with various functions

    All connective tissues are derived from embryonic

    tissue mesenchyme

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    Types of connective tissues

    1. Embryonic connective tissue

    a. Mesenchyme

    b. Mucous connective tissue (e.g. Whartons jelly in

    umbilical cord)2. Connective tissue proper

    a. Loose (areolar) connective tissue

    b. Dense connective tissues: regular and irregular

    3. Specialized connective tissues

    a. Bone

    b. Cartilage

    c. Blood

    d. Reticular tissues: in hemopoietic (hematopoietic)and lymphatic tissues

    e. Adipose tissue

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    Different types of connective tissues have a

    common embryonic origin: mesenchyme

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    e.g. Loose (areolar) connective tissue:- A model connective tissue

    - A common connective tissue type underlies all epithelia, surrounds

    blood vessels and nerves

    A. Cell types:

    - Fibroblasts

    - Fat cells (adipocytes)

    - Mast cells

    - Macrophages- Plasma cells

    - Lymphocytes

    B. Extracellular matrix:- Collagen fibers

    - Elastic fibers

    - Ground substance

    (tissue fluid, proteoglycans &glycoproteins)

    Basic organization of connective tissues

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    Loose and dense connective tissues

    e.g. in mammary gland

    Dense irregularconnective tissue

    Loose connective

    tissue

    Mammary gland

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    Loose (areolar) connective tissues

    Fine network of

    collagen/elastic/reticular fibers,

    with fluid-filled spaces Cells: fibroblasts & blood-borne

    cells

    Functions: most general

    functions of connective tissuese.g. support and binding

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    Dense irregular connective tissues

    Large amount of collagen fibers, hightensile strength/elasticity

    Fibers in random direction or layers

    Cells: mostly fibroblasts

    Functions: provides structuralstrength/elasticity

    Examples:

    dermis of skin, submucosa of

    digestive tract, fibrous capsules

    of joints, fascia

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    Dense regular connective tissues

    Dense parallel orientation ofcollagen fibers to withstand

    tensile forces in one direction

    Cells: fibroblasts

    Functions: to attach muscles to

    bones; bones to bones

    Examples: Tendons, ligaments

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    Adipose tissue (white)

    Large number of adipocytes,few fibers

    Functions:

    Tissue for energy reserve and

    insulation Endocrine function in regulation

    of energy metabolism and

    homeostasis

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    Brown adipose tissue

    - Tissue contains more blood supply; fat cells contain more mitochondriaand many lipid droplets.

    - It is present in aorta, kidney, neck and more abundant in the newborn.

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    Reticular connective tissues

    Locations: all lymphoid organs,

    hemopoietic tissue (bone marrow), liver

    Rich in reticular fibers (type III

    collagen; stained by silver staining) whichform a branched network to house various

    cell types for cell-cell interactions

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    Connective tissue cells

    B. Transient connective tissue cells

    (blood-born, immune functions):

    1. Lymphocytes2. Plasma cells (production of antibodies)

    3. Monocytes

    4. Granular leukocytes:

    neutrophils, eosinophils, basophils

    A. Fixed connective tissue cells:

    1. Fibroblasts (or myofibroblasts)

    2. Macrophages3. Adipocytes

    4. Mast cells

    5. Reticular cells in reticular tissues

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    Connective tissue cells

    F = fibroblast; L = lymphocyte; P = plasma cell

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    Fibroblasts

    Functions: synthesis of

    extracellular matrix

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    - Phagocytic cells derived from monocytes in blood- Free-moving in blood and tissues, or fixed in organs (e.g.

    lymph node, spleen, liver, skin)

    - Functions: phagocytose pathogens (e.g bacteria), dead

    cells, RBC etc; defense and immune responses

    Macrophages

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    Adipocytes (fat cells)

    - Cells contain a single large lipid droplet, with nuclei squeezedon periphery

    - Functions: synthesis and storage of fat, and endocrine

    regulations

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    Mast cells

    Cellular granules contain vasoactive and immunoreactive substances

    e.g. histamine, heparin Functions: mediate inflammation and allergic reactions

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    - Cells with a darkly stained nucleus and small amount of cytoplasm- Functions: various immune responses for defense and inflammation

    Lymphocytes

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    Plasma cells

    Cells with well-developed Golgi apparatus and RER Cells are active in antibody synthesis and differentiated from B-

    lymphocytes

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    MonocytesCells of Mononuclear Phagocytic System:

    - Macrophages (histiocytes) in connective tissues, peritoneal cavity- Kupffer cells in liver

    - Alveolar macophages in lungs

    - Macrophages in lymphoid organs

    - Osteoclasts in bone

    - Microglia in CNS

    - Langerhans cells in epidermis

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    3 Major types of connective tissue fibers:

    A. Collagen fibers (Types I, II collagens)

    - Tough fibers arranged in bundles; provides great

    tensile strengthB. Reticular fibers (Type III collagen + proteoglycans)

    - rich in hemopoietic (bone marrow) and lymphoidtissues, & liver

    - small and branched collagen fibers that form delicatenetworks to house cells for better cell-cell interactions

    C. Elastic fibers (elastin) and microfibrils (fibrillins)

    - long, thin fibers that allow for stretching- rich in dermis, large blood vessels & elastic cartilage

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    Connective tissue fibers (I)

    Collagen fibers

    Collagen fibers and fibrils

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    Ultrastructure of collagen fibrils and their association

    with proteoglycans

    Collagen fibrils show a characteristic 67-68 nm cross-striation

    pattern

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    Connective tissue fibers (II)

    Areolar connective tissue Aorta

    Elastic fiber

    Elastic fibers

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    Ultrastructure of elastic fibers

    Microfibrils

    Elastic fiber

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    Extracellular matrix = connective tissue fibers + ground substance

    Ground substance is a viscous and clear substance in fresh connectivetissues and contains mainly tissue fluid, proteoglycans, glycosaminoglycansand glycoproteins.

    It appears as empty spaces in histological sections but reacts to PAS

    reaction. At EM level, it appears as amorphous substance.

    Functions: very diverse from tissue support, molecular filter, cell adhesion,

    cell-matrix interactions to wound healing.

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    Major components of ground substance

    1. Proteoglycans = core protein + glycosaminoglycans (GAGs)

    2. Hyaluronic acid (hyaluronan)

    3. Glycoproteins e.g. fibronectin adhesion proteins

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    A proteoglycan molecule as seen under electron microscope

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    Glycosaminoglycans (GAGs)

    - GAGs are unbranched long chains of polysaccharides

    made up of repeating disaccharide units and components of

    proteoglycans

    Family of GAGs:

    - Chondroitin 4-sulfate

    - Chondroitin 6-sulfate

    - Dermatan sulfate

    - Heparan sulfate

    - Heparin- Hyaluronic acid (hyaluronan)