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1 connective tissue Dr. Zahiri

2 What's the main role of connective tissue? o Mechanical support o Material that connects and binds cells into tissues o Binds tissues to each other o Protection and Defense o Serving as a medium for exchange o Storage (water, ions, minerals, Growth factor) o Energy supply

3 What's the contents of connective tissue? cells connective tissue ECM Fibers Ground substance Fluid

4 The cells Mesenchyme Cells of connective tissue Adult Fixed Cells Fibroblast Macrophage Adipose cells Mast cells Undifferentiated mesenchyme cell Wandering Cells Lymphocytes Plasma cells Blood cells

5 Mesenchymal cells Small fusiform or stellate cells Not easily distinguished from fibroblasts Have delicate chromatin pattern Pluripotential

6 Fibroblast are most common cells of C.T. Produce and secrete ECM Active fibroblast has more cytoplasm include of developed RER, Golgi apparatus and euchromatic nucleus = activated (wound healing) Inactive fibroblast (Fibrocyte) has flattened nuclei, sparse cytoplasm Fibroblasts may differentiate to adipose cells or chondrocytes

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8 wound healing Myofibroblast : are modified fibroblasts They have bundle of actin similar to smooth muscle cells Abundant in wound healing ( wound contraction) Activated Fibrocyte = fibroblast

9 Macrophage (MPS) Origin: BM monocyte ( in blood) Macrophage in C.T. Irregular membrane surface; nucleus may be oval and is eccentric Size: micro Phagocytosis of cell debris and micro organisms Presenting antigens to lymphocytes RBC turnover in spleen Secretion of cytokins, enzyme In chronic inflammation form Epitheloid cells or multinuclear giant cells

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11 Mast cell Cytoplasm full of granules containing heparin, histamine, proteases, chemotactic factors, chondroitin sulphate Size: micro Centeric nucleus Originate from bone marrow stem cell

12 - Immediate hypersensitivity reaction - Slow reaction

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14 Plasma cell Common in intestinal lamina propria and glands secreting immunoglubulins such as lacrimal glands, salivary glands, and mammary gland Oval cell with basophilic cytoplasm, clock face nucleus Differentiate from B - lymphocytes Life span days

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16 Adipocyte

17 Others Neutrophils Eosinophils Basophils Lymphocytes - small, heterochromatic nucleus

18 Fibers Collagen fibers Elastic fibers Reticular fibers

19 Collagen fibers Staining (Eosin - pink; Mallory s - blue; Masson s green) Physical feature

20 Chemical components prolin lysin Hdroxy prolin Hydroxy lysin

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22 Biosynthesis

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25 Disorders: Osteogenesis imperfecta (gene or amino acid) Progressive systemic Sclerosis (fibrose- keloid) Vitamin C is a co-factor for prolin hydroxylase

26 Reticular Fibers (Collagen type III) Staining (Argylophilic- PAS) Physical feature Formative cell Disorders ( ehlers-danlos IV)

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29 (a) Connective tissue proper: loose connective tissue, areolar Description: Gel-like matrix with all three fiber types; cells: fibroblasts, macrophages, mast cells, and some white blood cells. Function: Wraps and cushions organs; its macrophages phagocytize bacteria; plays important role in inflammation; holds and conveys tissue fluid. Location: Widely distributed under epithelia of body, e.g., forms lamina propria of mucous membranes; surrounds capillaries. Elastic fibers Collagen fibers Fibroblast nuclei Epithelium Lamina propria Photomicrograph: Areolar connective tissue, a soft packaging tissue of the body (300x).

30 (b) Connective tissue proper: loose connective tissue, adipose Description: Matrix as in areolar, but very sparse; closely packed adipocytes, or fat cells, have nucleus pushed to the side by large fat droplet. Function: Provides reserve food fuel; insulates against heat loss; supports and protects organs. Nucleus of fat cell Location: Under skin in the hypodermis; around kidneys and eyeballs; within abdomen; in breasts. Adipose tissue Vacuole containing fat droplet Mammary glands Photomicrograph: Adipose tissue from the subcutaneous layer under the skin (350x).

31 (c) Connective tissue proper: loose connective tissue, reticular Description: Network of reticular fibers in a typical loose ground substance; reticular cells lie on the network. Function: Fibers form a soft internal skeleton (stroma) that supports other cell types including white blood cells, mast cells, and macrophages. Location: Lymphoid organs (lymph nodes, bone marrow, and spleen). White blood cell (lymphocyte) Reticular fibers Spleen Photomicrograph: Dark-staining network of reticular connective tissue fibers forming the internal skeleton of the spleen (350x).

32 (d) Connective tissue proper: dense connective tissue, dense regular Description: Primarily parallel collagen fibers; a few elastic fibers; major cell type is the fibroblast. Function: Attaches muscles to bones or to muscles; attaches bones to bones; withstands great tensile stress when pulling force is applied in one direction. Collagen fibers Location: Tendons, most ligaments, aponeuroses. Shoulder joint Nuclei of fibroblasts Ligament Tendon Photomicrograph: Dense regular connective tissue from a tendon (500x).

33 (e) Connective tissue proper: dense connective tissue, dense irregular Description: Primarily irregularly arranged collagen fibers; some elastic fibers; major cell type is the fibroblast. Function: Able to withstand tension exerted in many directions; provides structural strength. Location: Fibrous capsules of organs and of joints; dermis of the skin; submucosa of digestive tract. Nuclei of fibroblasts Collagen fibers Fibrous joint capsule Photomicrograph: Dense irregular connective tissue from the dermis of the skin (400x).

34 (f) Connective tissue proper: dense connective tissue, elastic Description: Dense regular connective tissue containing a high proportion of elastic fibers. Function: Allows recoil of tissue following stretching; maintains pulsatile flow of blood through arteries; aids passive recoil of lungs following inspiration. Location: Walls of large arteries; within certain ligaments associated with the vertebral column; within the walls of the bronchial tubes. Elastic fibers Aorta Heart Photomicrograph: Elastic connective tissue in the wall of the aorta (250x).

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36 What kind of tissue does this represent? Loose (areolar) connective tissue Where in the body can you find this tissue? delicate thin layers between tissues; present in all mucous membranes

37 What kind of tissue does this represent? Adipose tissue Where in the body can you find this tissue? fat

38 What kind of tissue does this represent? Dense connective tissue Where in the body can you find this tissue? tendons; ligaments

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40 Classification of connective tissue Emberyonic(mesenchyme) Adult ( Loose-Dense) Dense( Regular- Irregular)

41 Elastic Fibers Staining (orsein) Chemical components: oxytalan: GP: fibromodolin 1,2- fibrilin Oxytalan+ elastin= elaunin Elaunin + elastin in core= elastic aa of elastin: Desmosin - isodesmosin Disorders: marfan syndrom

42 Ground Substance An amorphous gel-like material it is not visible on slides, because it is removed during the preparation process composed of Glycosaminoglycans (GAG), Proteoglycans and multi adhesive Glycoproteins o function

43 Glycosaminoglycans (GAGs) or mucopolysaccharides GAGs are negatively charged, long, rod-like chains of repeating disaccharides(amino sugar + uronic acid) that have the capability of binding large quantities of water(hydrophilic) GAGs consist of Hyaluronic acid, Dermatan sulfate, Chondroitin sulfate, Keratan sulfate, Heparan sulfate Hyaluronic acid is nonsulfated and is a huge macromolecule and maybe20micrometerinlength

44 Different Types of GAGs

45 Proteoglycan complex Constitute a family of macromolecules each is composed of a protein core to which GAGs are covalently bonded (heparin( mast cell), Agrecan(ECM), Syndecans and fibroglycan(cell surface) They have large volume like a bottle brush Function: -Cell Binding to ECM.

46 Glycoproteins They have binding site for several components of extracellular matrix as well as for: integrin molecules of the cell membrane that facilitate the attachment of cells to the extracellular matrix (Fibronectin, Laminin, Chondronectin, Osteonectin, Entactin, Tenascin) Fibronectin is a v-shaped macromolecule that has binding site for extracellular components integrins of cell membrane,

47 Laminin is very large has three polypeptide chains, it is located in basal lamina and has binding site for: heparan sulfate, type IV collagen, entactin and cell membrane

48 Tenacin composed of 6 chains, it is distributed just in embryonic tissue and marks migratory pathway of some cells Entactin bind to laminin and type IV collagen Chondronectin and Osteonectin are similar to fibronectin and have binding sites for collagen type II and type I respectively

49 Integrins (Transmembrane Linkers) Integrins are transmembrane proteins but unlike other cell surface receptors, they are linked to cytoskeleton and structural member of extracellular matrix such as collagen so they also called Transmembrane Linkers Integrins are much more numerous than usual receptors they bind to extracellular component by weak bonds

50 Fluid Edeme phenomen

51 Specific connective tissue Adipose tissue Bone and cartilage Blood

52 Adipose tissue (Fatty tissue) 2A kind of connective tissue with many adipocytes 2Forms one of the largest organs of body % of body weight in men % of body weight in women 2Over 2 times as much stored energy as glycogen 2Subcutaneous adipose shapes body 2Shock absorber in soles of feet and palms 2Thermal insulation 2Fills space between organs

53 Two Types of Adipose Tissue Yellow, White or unilocular cells with one large fat droplet in cytoplasm Brown or multilocular cells with numerous smaller lipid droplets in cytoplasm and many mitochondria

54 Unilocular Adipose Tissue White to dark yellow depending on diet Most common form in adults Cells mm diameter Nuclei eccentric and flattened Lipid droplet has no membrane Heavily vascularized Cell number constant after early postnatal period

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56 Multilocular Adipose Tissue multiple droplets vascularization and many mitochondria, Central nucleus Has a lobular organization like glands Production of body heat by many mitochondria In human neonate, produces heat

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58 ذ و ر

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Most abundant and widely distributed tissues in the body Binds, support, and strengthen body tissues, protect and insulate internal organ, serve as

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