Connective Tissue 1 2013

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    CONNECTIVE TISSUE

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    Components of Connective Tissue

    Cells

    Fibers

    Ground Substance

    The proportion of these individual componentsvaries with each type of connective tissue.

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    Functions of Connective Tissue

    Structural support (capsules, bone,cartilage)

    Nutrition Defense (non-specific and immune)

    Cell growth and differentiation Cell migration

    Insulation

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    Connective Tissues: Special Characteristics

    Common embryological origin (from mesoderm)

    Innervated and Vascularized (direct blood supply)

    Cartilage is the only exception with no capillarybeds

    Extracellular Matrix ground substance (gelatinous glycoproteins)

    structural fibers (fibrous proteins, e.g. collagen,elastin, reticulin)

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    Types of Connective Tissues

    Connective Tissue Proper loose connective tissue

    dense (fibrous) irregular connective tissue

    dense (fibrous) regular connective tissue

    Specialized connective tissue adipose tissue

    reticular connective tissue

    Elastic connective tissue

    cartilage hyaline cartilage

    elastic cartilage

    fibrocartilage

    bone

    blood

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    Types of Connective Tissue

    Classified by the

    characteristics of the matrix

    gelatinous mineralized liquid

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    Connective tissue

    Elements:

    Ground substance

    Fibers

    Cells

    Extracellular matrix

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    Connective Tissue Structure

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    Connective Tissue Elements

    Ground substance:

    - Proteoglycans- large polysaccharide

    molecules bound to a protein core (like abottle brush).

    - Glycosaminoglycans (GAGs)are linearpolysaccharides composed of repetitivedisaccharide units, attached to proteoglycans

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    Glycosaminoglycans (GAGs)

    They trap water,

    hyaluronic acidgelatinous, separates cells, trapsextracellular fluid; lubricates joints; gives shape toeyeballs; fills body spaces

    chondroitin sulfatecapable of being mineralized;cartilage, bones, skin, blood vessels

    dermatan sulfateharder; skin, tendons, bloodvessels, heart valves

    keratin sulfate - still harder; bone, cartilage,cornea of the eyes

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    Ground Substance: Proteoglycan StructureThe proteoglycan monomer is composed of a core protein to whichGAGs are covalently bound. The PG monomer consists of aprox. 100

    GAG units joined to the core protein.

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    Edema is a condition of abnormally large fluid volume

    in the circulatory system or in tissues between thecells (interstitial spaces).

    Edema

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    Connective Tissue Elements Fibers

    Proteins that are embedded in the ground substance Provide structural support, adhesion, connect cells

    Collagen

    Tough; provide high tensile strength

    Also called white fibers

    Highly polymerized, gigantic molecules

    Tough, moderate flexibility

    Bone, cartilage, tendons, ligaments

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    Elastic fibers = elastin

    branched; smaller, thinner fibers than collagen

    very flexible and elastic but also strong

    can be stretched to 150% of its original length

    Also called yellow fibers

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    Connective Tissue Elements

    Reticular fibers (collagen type III)

    branched fibers that form delicate networks

    thin, less polymerized collagen fibers

    Elastic & reticular fibers require special stains to

    be seen in the light microscope

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    Cellsfewer, rarely touching, surrounded by a

    matrix immature forms (-blasts) secrete the matrix and can stilldivide

    once the matrix is secreted, the cells mature intocyteswhich have decreased cell divisions and secrete less matrix

    material fibroconnective, chondro- cartilage, osteo- bone etc.

    Fibroblasts/fibrocytes connective tissue proper

    Chondroblasts/chondrocytes cartilage

    Osteoblasts/ osteocytesbone

    Hematopoietic stem cells blood

    Connective Tissue Elements

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    Connective tissue

    Fibers

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    Fibers

    Long, rope-like protein extracellular polymers

    Present in variable proportions in the different

    types of connective tissues Three types: collagen, reticularand elastic

    fibers. Collagen and reticular fibers arecomposed of various types of collagen, elastic

    fibers are composed mainly of elastin

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    Collagen fibers

    Are the most abundant type ofconnective tissue fibers.

    There are many types of collagen thatdiffer in their origin, chemicalcomposition, functions, distribution and

    pathology

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    Collagen biosynthesis

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    Collagen biosynthesis

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    Collagen biosynthesis

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    The characteristicfeature is a pattern of cross- banding with a periodicity ofapproximately 64 nm wich results from the polymerisation of tropocollagen molecules

    such that each molecule overlaps the next by approx. one- quarter of its length.

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    Collagen fibrils, TEM

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    Collagen fibrils, TEM

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    Collagen fibers, SEM

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    Collagen fibers, SEM

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    Collagen types

    Fibril-forming collagen: types I, II,III, V and XI

    Fibril-associated collagen: types IXand XII

    Network-forming collagen: type IV

    Anchoring collagen: type VII

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    Collagen types

    Collagen I Forms fibrils, the most resistant to mechanical

    tension In: connective tissue of skin, bone, tendon,

    dentin and organ capsules

    Collagen II Forms fibrils In hyaline and elastic cartilage

    Collagen III

    In reticular lamina and reticular connectivetissue First collagen secreted in wound healing

    Collagen IV Forms a network in the basal laminae of

    epithelia

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    Elastic fibers

    Isolated, thin fibers or arranged in networks

    Localized in lung, urinary bladder, skin, aorta

    and elastic cartilage

    Special staining : orcein

    Are composed of 2 structural components: a

    central core of elastin and surrounding fibrillin

    microfibrils.

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    Elastic fibers, ORCEIN x40

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    Elastic fibers

    Elastin molecules are joined by covalent bondsto generate an extensive cross-linked network.

    Because each elastin molecule in the networkcan expand and contract like a random coil, the

    entire network can stretch and recoil like arubber band.

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    Elastic fibers

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    Marfans syndrome

    A defective gene forelastin -inherited

    Affects skin, mitralvalve and arteries(ruptured descendingaorta common)

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    RETICULAR FIBERS

    Provide a supporting framework for the cellular

    constituents of various tissues and organs.

    Thin fibers, forming networks

    Distribution : liver, spleen, lymph nodes,

    haematopoietic organs, endocrine glands.

    Special staining : silver impregnation

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    Reticular fibers, Silver Impregnation x40

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    Connective

    TissueCells

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    Connective tissue cells

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    Connective tissue cellsclassification

    Cells that produce/degrade the extracellularmatrix

    fibroblasts, osteoblasts, condroblasts, macrophages

    Metabolic cells adipocytes

    Defense (specific/non-specific) Lymphocytes, macrophages, neutrophils, mast cells,

    plasma cells

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    Fibroblast

    The most frequent cell

    LM- Elongated cells, 20 mm, branched

    processes, basophilic cytoplasm, oval ,euchromatic nucleus, 1 or 2 nucleoli

    TEM-abundant RER and a prominent

    Golgi apparatus.

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    Fibroblasts

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    Fibroblasts

    Produce:

    Elements of the extracellular matrix:procollagen, proelastin, fibrillin, GAG, PGand GP;

    Enzymes: matrix metalloproteinases -collagenase (degrades collagen at neutral

    pH), elastase; Growth factors

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    Fibroblast

    Properties:

    Ability to switch its fenotype

    fibroblast

    fibrocyte Can change shape

    Mobile

    Induces differentiation of surroundingcells

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    Myofibroblasts

    Are fibroblasts that contain actinfilaments associated with dense bodies -

    fibronexus

    Have a contractile function as well as a

    role in secretion of extracellular matrix.

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    Fibrocyte

    Less active than fibroblasts LM - smaller, elongated/spindle shaped,

    lesser cytoplasm, a few short unbranched

    processes Eosinophilic cytoplasm Elongated and heterochromatic nucleus TEM-sparse RER and a small Golgi

    apparatus.

    Fibroblasts fibrocytes

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    Fibroblasts, fibrocytes

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    Fibroblasts, fibrocytes, HE 400x

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    Unilocular (white) adipocyte

    LM- round (when isolated) orpolygonal in groups One large lipid droplet (inclusion)A thin rim of cytoplasm at the periphery that

    contains a flattened, heterochromatic nucleus(signet ring)

    TEM-small Golgi complex, RER,mitochondria and microfilaments.

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    White adipocytes, col. HE, 400x

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    White adipocytes, col. SUDAN III , 400x

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    Multilocular (brown) adipocyte

    Smaller cells than the white adipocytes

    Many small lipid droplets in the cytoplasmfoamy look

    Round, central nucleus

    Mostly found before birth and in neonates

    Role in thermogenesis

    TEM- many mitochondria (the high concentration ofcytochromes in the mithocondria is responsible for the

    brown color of aggregates of multilocular adipocytes; thebrown color is also due to high vascularization-3capillaries for each brown adipocyte).

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    Brown adipocytes, col. AZAN, 600x

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    Brown adipocyte

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    Brown adipocytes (3-4 capillaries/1 brown adipocytes)

    R ti l ll

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    Reticular cells

    Produce reticular fibers, which form the fine structuralnetwork of organs such as the lymph nodes, spleenand bone marrow.

    Star-shaped cells with long and thin processes thatestablish anchoring junctions with neighboring cells;round, central, pale nucleus.

    !!!!! Should not be confused with the reticulocyte,

    an immature erythrocyte.

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    Cytoreticule

    Double reticule

    =Reticular cells

    +Reticular fibers

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    Reticularcells &reticular fibers, HE&Silver

    Impregnation, 400x

    M l t

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    Melanocytes

    Cells of ectodermal origin Consequently migrates to dermis,

    epidermis, iris, hair root

    Star-shaped cell, with many branchedprocesses; 30 mm

    Melanin granules in the cytoplasm, dark-brown;

    Round, central, small nucleus

    M l

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    Melanocytes Melanosomesvisible in EM:

    Primary melanosomes are Golgi vesiclesthat accumulate thyrosin (the melaninprecursor) and thyrosinase, located at thebase of cell processes

    Secondary melanosomes are heterogenousvesicles (EM) that accumulate melanin

    Tertiary melanosomes are found at the tips

    of the cell processes; they are releasedfrom melanocytes and engulfed bysurrounding cells (keratinocytes)

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    Melanocyte, 600x

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    Macrophages

    Derived from peripheral blood monocytes, Involvedin phagocytosis and inflammatory response

    A family of cells with various shapes, localizationsand names:

    Histiocytes: connective tissueKupffer cells: liver

    Langerhans cells: intra-epidermal

    Alveolary macrophages/Dust Cells : lung

    Osteoclasts: boneMicroglia: central nervous system

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    Macrophages

    They are part of themononuclear phagocytesystem(MPS/ RES).

    Macrophages of the connective tissue: LM - about 30 mm,ruffledmembrane (irregular

    shapes), acidophilic lysosomes in the cytoplasm, canhave various heterogenousinclusionsingestedmaterial

    Round, oval or kidney-shaped, eccentric nucleus;can have nucleoli

    TEM-numerous lysosomes, phagosomes andpseudopodia, abundant RER, SER, mitochondria andGolgi complex.

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    Macrophage

    Main function: phagocytosis Triggered by a specific interaction between

    membrane receptors and ligands. Consequences:

    Cell movement towards target particle Pseudopodia formationengulfment Respiratory burst Secretion: cytokines, interferon, complement

    & coagulation factors Production of matrix metalloproteinases

    Alveolar macrophages vital staining and HE 600x

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    Alveolar macrophages, vital staining and HE, 600x

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    Macrophage, TEM

    M t ll

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    Mast cells Localized in most of the loose connective tissue

    areas, along blood vessels LM - Large, Oval cell, 20-30 mm

    Cytoplasm has numerous basophilic, metachromaticgranules (elements of a cell stain in a different color from that of thedye solution- toluidine blue)

    Round, small and central nucleus

    TEM-granules, an extensive Golgi complex,

    cisternae of RER, free ribosomes, mitochondriaand numerous microvilli and folds.

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    Mast cells

    Granules contain heparin or chondroitin sulfate,histamine, Eosinophil Chemotactic Factor, etc.

    The content can be released -degranulation.The process is triggered by chemical, physicalstimuli, or through binding of antigen-IgEcomplexes by specialized receptors

    Degranulation is mediated by cAMP and leadsalso to leukotriene synthesis

    Mast cells, Toluidine blue stain

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    Mast cell, TEM

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    ,

    Plasma cells

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    Plasma cells

    Found in lymphoid organs (lymph nodes,spleen, bone marrow) and connective tissuesassociated to the respiratory and digestivemucosae

    Originate in B lymphocytes, that are terminallydifferentiated as a response to antigenchallenge

    Secrete immunoglobulins (antibodies): IgM,IgG, IgA, IgE

    Plasma cells

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    Plasma cells LM

    Ovoid/ pear shaped cells

    Basophilic cytoplasm (due to abundant RER), with aperinuclear pale area (Golgi apparatus); can containacidophilic Russel bodies (secretory granules)

    Eccentric nucleus, with hetero- and euchromatin in acharacteristic pattern:cart wheelorclockface(theheterochromatin resembling the spokes of the wheel or the numbers on

    a clock), visible nucleolus.

    TEM- extensive Golgi complex, abundant RER,secretory granules (Russel bodies), free ribosomesand mitochondria.

    Plasma cells TB stain

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    Plasma cells, TB stain

    Pl ll l MGG 400

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    Plasma cell, col. MGG, 400x

    Plasma cell, TEM

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