1. Connective Tissue

2. GROUND SUBSTANCE 2

3. CLINICAL CASE A 2-year-old girl presented with coarse, thick hairy skin all over the body, a tuft of hair in the parietal region, coarse facial features and a prominent forehead with a large tongue, hepatosplenomegaly and skeletal deformities. Mucopolysaccharides excretion spot test of the urine was positive; and an assay for glycosaminoglycans in the urine was also high, which confirmed the clinical diagnosis of Hurler syndrome. 3

4. HURLER SYNDROME 4

5. 5 The Role Of Extracellular Matrix Collagen: Tensile properties Elastic Fibers: Elasticity and resilience Non-collagenous Glycoproteins: Cell adhesion and motility Glycosaminoglycan/Proteoglycans: Hydration

6. 6 Glycosaminoglycans (GAGs) Disaccharide units: N-acetylglucosamine or N-acetylgalactosamine Sulfated compounds + uronic acid sugar = NEGATIVE CHARGE Attract osmotically active cations = heavily hydrated matrix Linked to a core protein (except hyaluronic acid)

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10. 10 GAGs I: Hyaluronic acid: synovial fluid, cartilage II: Chondroitin sulfate: cartilage, bone Dermatan sulfate: skin, heart valves III: Heparin: lung, skin, mast cells Heparan sulfate: basal laminae IV: Keratan sulfate: cornea, cartilage, IV disks I: Hyaluronic acid: synovial fluid, cartilage II: Chondroitin sulfate: cartilage, bone Dermatan sulfate: skin, heart valves III: Heparin: lung, skin, mast cells Heparan sulfate: basal laminae IV: Keratan sulfate: cornea, cartilage, IV disks

11. - With the exception of hyaluronic acid all GAGs are covalently linked to protein core forming proteoglycans giving the appearance of bottle brush *hyaluronic acids are large molecules with thousands of carbohydrate chains compared to 100 s or less in other GAGs - bound by electrostatic bounds to the protein core to form proteoglycans and does not have sulfated side group however other proteoglycans are indirectly linked to it.

12. 12 Proteoglycans = core protein from which many GAGs extend large complex aggregates act as binding sites for growth factors and other cytokines

13. Clinical correlation The degradation of proteoglycans is carried out by several cell types and depends on the presence of several lysosomal enzymes. Deficiency in lysosomal enzymes causes GAG degradation to be blocked, with subsequent accumulation of these compounds in tissue as seen in diseases like Hurler syndrome, Hunter Syndrome,Sanfilippo syndrome and Morquio syndrome 13

14. 14 Glycoproteins Fibronectin Laminin Entactin Tenascin Chondronectin Osteonectin Fibronectin Laminin Entactin Tenascin Chondronectin Osteonectin Proteins predominate

15. 15 Fibronectin Matrix-adhesive glycoprotein Cell-surface fibronectin Plasma fibronectin Domains for binding: collagen, heparin, cell surface receptors and CAMs MEDIATES CELL ADHESION

16. 16 Laminin Secreted by epithelial cells adjacent to the basal laminae; in the external laminae of the muscle and Schwann cells Binds: cell-surface receptors, heparan sulfate, type IV collagen, entactin ANCHORS THE EPITHELIAL CELL TO THE BASAL LAMINA

17. 17 Entactin Component of the basal external laminae Binds laminin Links laminin with type IV collagen in the lamina densa

18. 18 Tenascin Secreted by glial cells in the developing nervous system Role in cell-matrix migration Abundant in embryonic tissues

19. 19 Chondronectin Attaches chondrocytes to type II collagen Binding sites for collagen, proteoglycans and cell-surface receptors Role in the development and maintenance of cartilage

20. 20 Osteonectin Found in bone Links minerals to type I collagen and influences calcification by inhibiting crystal growth

21. Classification of Connective Tissue Loose connective tissue Dense connective tissue Elastic Tissue Reticular connective tissue Adipose Tissue Cartilage and Bone Blood Connective Tissue Proper Specialized connective tissue

22. 22 Types of Connective Tissue Proper Loose or areolar less dense fibers Dense more fibers than cells Proper Loose or areolar less dense fibers Dense more fibers than cells

23. 23 Loose-Areolar Connective Tissue Well vascularized, flexible and not very resistant to stress More abundant than dense connective tissue

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25. 25 Loose

26. 26 Dense Irregular Connective Tissue Contains fibers that have no definite orientation Characteristic of the dermis and the capsule of many organs

27. 27 Dense irregularLoose

28. 28 Dense irregular

29. 29 Dense Regular Connective Tissue Contains fibers and attenuated fibroblasts that are arranged in a uniform parallel fashion Tendons and ligaments May be collagenous or elastic

30. 30 Dense regular - tendon

31. 31 Tendon – longitudinal

32. 32 Tendon - transversal

33. 33 Elastic Tissue Coarse, branching elastic fibers with a sparse network of collagen fibers Fibroblasts fill the interstitial spaces Dermis, lungs, elastic cartilage, elastic ligaments, In large vessels forms fenestrated sheats

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36. 36 Reticular Tissue Network of branched of branched reticular fibers : type III collagen Livers sinusoids, smooth muscle cells, fat cells Stroma of lymphatic organs, bone marrow and endocrine glands Forms the reticular lamina of basement membranes

37. 37 Pathology Scurvy (hydroxolases – collagen fibers) Wound healing (fibroblast) Ehlers-Danlos syndrome (collagen defects) Marfan syndrome (elastic tissue) Edema Hay fever and Asthma Anaphylactic shock Obesity

38. 38 FunctionGlycoproteins Structural moleculeCollagens Lubricant and protective agentMucins Transport moleculeTransferrin, ceruloplasmin Immunologic moleculeImmunoglobins, histocompatibility antigens HormoneHuman chorionic gonadotropin (HCG), thyroid-stimulating hormone (TSH) EnzymeVarious, eg, alkaline phosphatase Cell attachment-recognition siteVarious proteins involved in cell-cell (eg, sperm-oocyte), virus-cell, bacterium-cell, and hormone cell interactions Interact with specific carbohydratesLectins, selectins (cell adhesion lectins), antibodies ReceptorVarious proteins involved in hormone and drug action Affect folding of certain proteinsCalnexin, calreticulin Regulation of developmentNotch and its analogs, key proteins in development Hemostasis (and thrombosis)Specific glycoproteins on the surface membranes of platelets