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Block 1: Pathology Dr. Rosezweig Test 1: Connective Tissue Introduction maintain form of organs throughout body major constituent: ECM o diff protein fibers and ground substance o ground substance: anionic, hydrophilic GAGs and multiadhesive glycoproteins extracellular volume exceeds that of cells derived from embryonic mesoderm which differentiates into mesenchyme (and/or mucoid tissue) o mesenchyme: diff into wide variety of adult forms of CT o small amts mesenchyme in adults (eg: wound healing) Mesenchyme: viscous ground substance with few collagen fibers undiff., spindle-shaped cells large, euchromatic nuclei prominent nucleoli high levels of synthetic activity. ground substance rich in hyaluronan, little collagem Cells of Connective Tissue Fibroblasts o most common o produce/maintain most of extracellular components o “spindle” shaped o large, active nuclei o eosinophilic cytoplasm o can distinguish between active/quiescent fibros: active: large, euchromatic nuclei, basophilic cytoplasm quiescent: smaller, more heterochromatic nuclei Cells of immune system (loose CT) o macros derived: monocytes bone marrow aka “histiocytes” o mast cells derived: basophils bone marrow abundant basophilic granules located near small blood vessels oval shaped o plasma cells derived: B lymphocytes Ab producing cells basophilic cytoplasm abundant RER spherical, eccentrically placed nucleus peripheral clumps heterochromatin “clock face” appearance more abundant in infected tissue (duh!) o other immune cells will enter CT in inflammatory situations lymphocytes, neutros, eosinophils ECM Fibers 1 Block 1: Pathology Dr. Rosezweig Test 1: Connective Tissue o elongated structures from proteins that polymerize after secretion from fibros Collagen Fibers o triple helical structure; 2 identical chains (1) and an additional chain, differing slightly in chemical composition (2) o extremely strong and resistant to shearing and tearing forces o secreted by fibroblasts o key element of all connective tissues o 28 diff types o fibrillar collagens (eg: types I, II, III)- bundle together to form large fibers o sheet forming collagens (eg: type IV)- produced by epithelial cells, form basal lamina of epithelia o linking/anchoring collagens (eg: type VII)- link other collagens to one another, and to other components of ECM o Type 1 collagen bundled together to provide increased tensile strength, forming large, easily visible structures with H&E staining o Diseases of mutated Collagen: Ehler-Danlos: diff forms due to mutations in diff genes most affect skin, joints, blood vessels osteogenesis imperfecta: point mutation in collagen gene brittle bone disease, and other symptoms scurvy: vitamin C used as cofactor for an enzyme involved in extracellular assembly of collagen bleeding gums, hemorrhages Reticular Fibers o type III collagen o extensive network of extremely thin fibers o secreted by fibroblasts o “scaffolding” of other cells structure to certain organs o component of reticular lamina of basement membrane o stained with silver salts (RFs are argyrophilic) o supportive stroma in most lymphoid and hematopoietic organs and many endocrine glands o heavily glycosylated type III collagen produces black argyrophilia Elastic Fibers o physical properties similar to rubber o stretch and return to original shape o cross-linked elastin o special stains: eg: aldehyde fuschin o bundled together and woven into sheets o secreted by fibroblasts and smooth muscle cells o multiple random-coild domains that can be stretched o desmosine: cross-links the elastin subunits 4 converted lysine’s in two elastin molecules make the cyclice desmosine molecule o Marfan syndrome mutation in gene for fibrillin (scaffolding protein in elastic fibers) long limbs, dislocated lenses, aortic root dilation Ground Substance highly hydrated, transparent complex mixture of macromolecules from… o GAGs 2 Block 1: Pathology Dr. Rosezweig Test 1: Connective Tissue o proteoglycans o multiadhesive glycoproteins fills space between fibers in CT and varies in consistency from fluid to semi-solid Glycoproteins: globular proteins with branched oligosaccharide side-chains; polypeptide content> polysaccharide content proteoglyclans: core of protein, with one/many side chains of sulfated GAGs as well as branched oligosaccharides; more carbs than glycoproteins o aggrecan: major proteoglycan in cartilage hyaluronan= core protein hydrated chondroitin sulfate and keratan sulfate side chains attached by link proteins Types of Connective Tissues Embryonic CT o Mesenchyme: progenitor of all other connective tissues cells have long processes and matrix almost totally lacking in fibers o Mucoid: similar to mesenchyme except for presence of small collagen fibers Connective Tissue Proper o Loose (areolar) CT packing, anchoring, and/or embedding material in virtually every organ fluid-like ground substance with random collagen and elastic fibers fibrosis: when this CT replaces other tissues after injury o Dense IRRegular CT large collagen fibers arranged in random fashion few elastic and reticular fibers; very little matrix tough fibrous sheets (eg: capsules that surround various organs) dermis of skin o Dense Regular CT densely packed fibers coursing parallel to each other ligaments and tendons Specialized CT o Reticular CT branching network of reticular fibers that form the framework of certain organs o Adipose Tissue lipid storing cells embedded in reticular framework usually found in association with loose CT energy storage, thermal insulation, shock absorption Types: unilocular (white fat): lipids stored in one large vacuole that occupies majority of cell multilocular (brown fat): lipids in many vacuoles o heat production- energy produced in krebs cycle lost as heat bc of uncoupling protein in mitochondria o animals that hibernate have increased amts of brown fat o cartilage o bone o blood 3