CONNECTIVE TISSUE

1. CONNECTIVE TISSUE 2 general types: CT Proper and CT Supportive CT Proper classified on the basis of intercellular material (types, arrangement and density of fibers). Intercellular material contains a variety of fibers (protein composition) embedded in a semi-fluid ground substance (amorphous intercellular substance) Fibers + ground substance = Matrix.

2. Collagen Fibers Collagen Fibers = actually a family of > 20 related proteins Most abundant protein in the body (30% of dry weight) 4 Categories according to structure/function: Form long fibrils Fibril-associated collagens (bind collagen fibers to extracellular matrix) Form anchoring fibrils (e.g., attach basal lamina to underlying reticular fiber layer) Form networks (e.g., basal lamina)

3. Collagen Fibers – Type 1 Collagen Most abundant collagen type 1-20 µm in diameter, indeterminate length, unbranched Fibers are wavy in tissues, provides some capacity for stretch even though the actual fibers are relatively inelastic Divisions of Collagen Fiber: Fiber ? Fibril ? Microfibril = Tropocollagen Molecule Tropocollagen molecule composed of 3 polypeptide chains forming a right-handed superhelix Tropocollagen molecules staggered giving periodic striations to fibril (only visible under EM). Periodicity of striations = 64 nm (approx. 25% of length of tropocollagen molecule)

5. Elastic Fibers Thinner than collagen fibers (1-4 µm) Threadlike and highly branched, great elasticity Form sheets (25 µm diameter) in elastic ligaments Stain poorly in H&E, stain w/ orcein or resorcin-fuchsin Homogenous rather than fibrillar ultrastructure (glycoprotein microfibrils form tube enclosing amorphous elastin)

7. Reticular Fibers Delicate collagen fibers (composed of tropocollagen) 0.5-1 µm in diameter Lack staining properties of collagen so don't stain with H&E, special stain = silver impregnation (argyrophilic fibers) Branch and interconnect to form delicate network Non-elastic, found in tissues with little tension (e.g., glands, lymph nodes) Also found in other tissues providing support for capillaries, nerves and muscle cells

9. Ground Substance Transparent, colorless, homogenous, semi-fluid Functions as a medium through which nutrients and waste products can diffuse between capillaries and cells Composed of glycosaminoglycans (GAGs) and glycoproteins GAGs = polysaccharides usually containing two types of alternating monosaccharide units, at least one of which has N-containing prosthetic group.

10. Cells of CT Proper Undifferentiated Mesenchymal Cells = embryonic, some persist in adult as precursors to other CT cells Stellate with elongated nuclei and coarse chromatin Fibroblasts = responsible for production of fibers and ground substance Stellate with wide cytoplasmic processes (difficult to see) when active, in side view appear spindle-shaped Basophilic cytoplasm Prominent elongate or oval nucleus with prominent nucleoli and fine granular chromatin Old inactive fibroblasts = fibrocytes, have less basophilic cytoplasm and condensed nucleus

12. Cells of CT Proper Fat Cells = found in areolar (loose) and adipose CT - not capable of mitotic division as adult cell; 2 Types: White Fat = most common, serves as storage tissue for lipid (energy reserve) During development accumulates lipid droplets which coalesce to form a large central droplet (unilocular); cell therefore takes on "signet-ring" appearance - cytoplasm = ring, flattened nucleus on periphery = signet Brown Fat = occurs only in mammals; relatively scarce, found in anterior regions of body (e.g., between scapulas) in neonates, hibernators and cold-adapted mammals. Functions in thermogenesis = heat production Histologically: contains multiple lipid droplets (multilocular), central nucleus, high numbers of mitochondria; brown color from high concentration of cytochrome in mitochondria

14. Cells of CT Proper Macrophages = phagocytic cells forming from monocyte (= histiocyte) Almost as numerous as fibroblasts in areolar CT May be attached to collagen fibers (fixed) or loose within matrix (free) When stimulated, fixed macrophages detach and migrate to sites of bacterial invasion or tissue injury Nucleus stains darkly and is indented Cytoplasm often round, but can be variable in shape

15. Cells of CT Proper Mast Cells = large, rather round cells with basophilic granules in cytoplasm and central pale nucleus Similar to basophil, but may arise from several sourcesnot just bone marrow Usually found associated with blood vessels Granules contain heparin and histamine Stimulation by antigen or tissue damage results in degranulation and an allergic response Heparin = clearing of plasma lipids, blood anticoagulant Histamine = vasodilation, increased permeability of venules, mediates inflammation

17. Cells of CT Proper Chromophores = (e.g., Melanoblast/cyte - brown/black) Melanoblasts/cytes derived from neural crest cells embryonically Have long cytoplasmic processes When stimulated (UV light) produce pigment (melanin), leads to suntan Found under skin epidermis Plasma Cells = rare in most CT, more common in lymph nodules and reticular CT of blood-forming organs Resemble lymphocytes but are larger with more cytoplasm; cytoplasm basophilic Nucleus with chromatin like "cartwheel“ Derived from hemopoietic stem cells and B-lymphocytes; major function = Ab production

19. Cells of CT Proper WBCs - most common types in CT are lymphocytes and eosinophils

20. CT Proper Types Mesenchyme = embryonic, mesenchymal stellate cells in semi-fluid matrix; enables cells to move about easily Mucous = transient tissue appearing in normal development of CT and as Wharton's Jelly of umbilical cord Contains large stellate fibroblasts Matrix contains delicate collagen fibers inmucoprotein gelatinous ground substance

23. CT Proper Types Areolar (Loose Irregular) = very common, serves connective and supportive functions Most common cells are fibroblasts and macrophages (histiocytes)

24. CT Proper Types Adipose - 2 Types: White Fat = aggregations of unilocular fat cells, each cell surrounded by a web of reticular fibers Also occurring are fibroblasts, lymphocytes, eosinophils, magrophages and mast cells Penetrated by blood vessels, dealing with mobilization and deposition of fat; serves as a storage tissue for lipid Brown Fat (BAT) = aggregations of smaller multilocular fat cells Very rich vascularization Supporting tissue similar to WAT

26. CT Proper Types Reticular = composed of reticular fibers and reticular stellate cells (appearance like mesenchyme with reticular fibers) Forms framework of lymph organs, bone marrow and liver Crowded with lymphocytes and other cell types (principally blood cells)

27. CT Proper Types Dense Irregular = like a densely packed areolar CT with little ground substance Majority of fibers are collagen, elastic and reticular fibers also present in lesser numbers Principal cell = fibroblast Locations: fascia, dermis of skin, fibrous sheath of bone (periosteum) and cartilage (perichondrium), fibrous capsules of lymph node, liver, some glands

28. CT Proper Types Dense Regular = fibers are densely packed and lie parallel to each other Provides great tensile strength Found in tendons, ligaments, aponeuroses (flat sheets connecting muscle to bone), some organ capsules

29. Tendon Structure Collagen fibers = primary tendon bundles (covered by areolar CT = endotendineum) Primary bundles grouped into fascicles (covered by dense CT = peritendineum) Fascicles grouped into tendon (covered by dense CT = epitendineum) Fibrocytes (inactive) occur in longitudinal rows between collagen fibers, in c.s. fibrocytes appear stellate ("winged fibroblasts") Ligaments and aponeuroses similar, but arrangement less regular

30. Tendon Structure

31. CT Proper Types Elastic = coarse parallel elastic fibers bound together by a small amount of delicate CT with fibroblasts, collagen fibers Frequent branching and fusion of elastic fibers Found in elastic ligaments (e.g., true vocal cords, surrounding aorta as fenestrated membranes) Lamellated = condensation of dense irregular CT around blood vessels, nerves and gland ducts