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35 Cards in this Set
- Front
- Back
Connective tissue types
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- CT proper - directly under skin - structural, dense & anti-microbial
- Bone - support, protection, hematopoiesis - Cartilage - shock absorber - Blood - immune mechanisms - Fat - TAG under skin, on organs |
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CT functions
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- Structural - bone/cartilage
- Defense - immune response, ECM thicket - Transport - nutrients/gasses - Storage - fat, water, ions - Repair - wound healing |
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CT Focus - Changes with age
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- Aging compromises all of these functions
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Elastosis
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- Appearance of wrinkles, bags, sags
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Aging effects on CT
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- Aging is chronic, terminal disease
- Elastosis - Change in fat amount/distribution - Thinning of bones (osteopenia/osteoporosis) - Cartilage degradation - reduced joint mobility - Weakening of immune system, wound healing |
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CT degradation factors
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- Age - degradation acclerates with age
- Genetics - some faster than others - # stem cells, length of telomeres - Lifestyle - smoking, sunlight, diet, exercise - Disease - impacts variable CTs |
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Layers of skin
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- 3 layers
- Epidermis - Dermis - Subcutaneous layer (fat, etc.) |
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Dermis contents
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- Ground substance - fills spaces not occupied by cells, fibers
- Collagen (Type I) - thick, pink ribbons - Elastic fibers - thin, black fibers - Fibroblasts - making structural fibers - Neutrophils, macrophages, lymphocytes, mast cells |
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Ground substance
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- Fills CT space in between cells, fibers
- Composed of glycosaminoglycans and structural glycoproteins - Glycosaminoglycans (linear poly-disaccharides) -> proteoglycans (linear poly-saccharides covalently bound to protein core) -> Proteoglycan aggregates - associated with hyaluronic acid |
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Glycosaminoglycan (GAG) disaccharide units
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- Highly negatively charged @ pH of life!
- (-) attracts hydration sphere - Very viscous, non-compressible - turgid, stiffness - Chondroitin-6-sulfate = Cartilage, bone, skin, vessels - Dermatan sulfate - Skin, tendon, vessels - Hyaluronate - Cartilage, synovial fluid - Cartilage - keratan sulfate - Mast cells - Heparin |
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Core proteins
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- Glycosaminoglycans bind to these, form proteoglycans
- Long GAG binding area in middle (most of protein) - Short hyaluronic acid binding domain (HABR) at N-terminus - Syndecan = heparin sulfate - Versican = chondroitin sulfate - Aggrecan = chondroitin sulfate |
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Proteoglycan aggregate
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- GAG disaccharide units -> GAG's
- Core protein covelently bound to GAG's -> proteoglycans - HABR binds hyaluronic acid via link protein -> proteoglycan aggregate |
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Structural multiadhesive glycoproteins
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- Laminin and Fibronectin
- Laminin = only found in basement membrane! - Fibronectin = in dermis (ground substance) - dimer - multiple binding sites - imparts structural integrity to CT proper |
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Integrin receptors
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- Single-pass membrane proteins - bind to ECM
- 2-way signalling to/from ECM via these - Can bind cells, collagens, GAGs, proteoglycans, other glycoproteins |
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Collagen
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- Most abundant protein in body (30%) - Seen as pink ribbons histologically
- Very inelastic - tensile strength of steel - Injections can help "beef up" tissue - Cosmetic (lips, etc.) and medical (urinary incontinence) - Large segments of Gly-X-Y repeats(often X = proline, Y = hydroxyproline) |
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Collagen organization
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- Tropocollagen = combination of 3 collagen helices
- Fibril - bundle of tropocollagen molecules - Fiber - bundle of fibrils - Spontaneously assembles outside of cell |
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Collagen synthesis
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- Secretory protein - transcribed on RER surface
- Pre-procollagen - while being transcribed, translocating into RER lumen - Some residues are hydroxylated or glycosylated - Signal peptide cleaved -> procollagen - Registration peptides at N, C terminals orient direction - Hsp47 assists with orienting, forming triple helix - Shipped to Golgi - laterally associate with one another - Exported from cell - registration peptides cleaved - spontaneous assembly, crosslinking |
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Collagen staining with heavy metals (Pb)
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- Very distinctive striations!
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Fibrillar collagens
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- Type I, II, and III
- We are mostly composed of Type I - Type I = fibrils and fibers - Type II = fibrils only - Type III - fibrils and fibers |
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Network collagens
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Type IV
- Also tri-helical structure - interrupted by non-helical segments throughout - flexibility! - Small N-, large C- terminal domains - C binds C (dimers), N binds N (tetramers) - Flexibility and binding allows creation of expansive 2-D network - Forms basement membrane - Interacts with laminin, entactin (glycoprotein), perlecan (proteoglycan) |
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Goodpasture syndrome
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- Autoimmune disease attacking Type IV collagen
- Cough blood, blood in urine - Treatment - immunosuppresive drugs, corticosteroids |
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Ehlers-Danlos Disorders
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- Resulting from defects in collagen or collagen-producing cells
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Ehlers-Danlos Type IV
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- Mutation in Type III collagen - autosomal dominant
- Strange-shaped face, bulging eyes, translucent skin - Easy bruising, small and major vessels rupture |
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Reticular fibers
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- Primarily Type III collagen - heavily glycosylated
- Very thin, not as strong as Type I collagen - Present in capillary layer of skin, smooth muscle - Also in spleen, lymph node, bone marrow (hematopoietic organs) - Not visible with H & E - Stain black with silver salts (from glycosylation) |
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Elastic fibers
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- 3 stages of development
- Stage 1 = Oxytalan fibers - 10-12nm wide microfibrils (found in dermis, zonule fiber of eye) - Organize scaffold - Stage 2 = Elaunin - Fibroblast irregularly deposits elastin between oxytalan fibers - Stage 3 = Elastic fibers - elastin deposition increases, occupies center of scaffold |
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Cutis laxa
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- Extremely rare genetic disorder affecting elastic fiber production
- Saggy, inelastic skin - Other tissues affected also (heart, vessels, joints, lungs, etc.) |
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Wrinkle histology
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Compare Non-UV exposed skin, UV exposed skin, and UV exposed wrinkles
- UV exposed skin has significant loss of oxytalan fibers compared to non-exposed - Oxytalan even more rare below wrinkle - Chondoitin (GAG) decreases with UV exposure - Type IV collagen in basement membrane goes - epidermis collapses in on dermis - no structural support - Fibroblasts not making much collagen/elastin - not making it well, either - Tangled, congealed, less functional - Result = wrinkles and sags |
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Experiment with filler injections in old people butts
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- Fibroblasts, CT = very sensitive to pressure
- When injected with GAG filler - fibroblasts put out more, higher-quality collagens and elastins |
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CT cell lineage
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- CT cells come from undifferentiated mesenchymal cells
- These give rise to osteoblasts, fibroblasts, adipocytes, etc. - Wispy cytoplasm, prominent nuclei |
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Fibroblasts
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- Derived from mesenchymal stem cell - spindle shaped
- Most prevalent cells in CT - Stain same color as collagen - seen as "nuclei" floating in sea of pink"... |
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Adipocytes
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White/yellow fat = looks like chicken wire in H&E staining (completely black with osmium)
- Possible nucleus squished against the side - Brown fat = central nucleus, cells stain darker, small lipid droplets inside |
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CT & wound healing
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3 Stages!
1) Inflammation - Macrophages, neutrophils, mast cells come in, clean up, create inflammatory response, recruit help 2) Cell proliferation and matrix creation - New cells, ECM, fibers, vessel repair 3) ECM remodeling - constant process - all tissues continue to turn over |
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Mast cells
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- Contain basophilic granules, often found in breast tissue
- heparin, histamines, inflammatory cytokines |
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Plasma cells
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- Make immunoglobins
- ID by "clock-face" nuclei - Has extensive ER - can see this b/c cytoplasm will be basophilic |
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Distinguish between loose/dense CT
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Loose CT = Significant ground substance (white in H&E stain) - looks spacious
- Supports epithelial tissue - Delicate consistency, flexible, well vascularized - Contains fibroblasts, macrophages, lymphocytes, plasma cells - Has collagen, elastic, reticular cells - Dense, irregular CT = Fewer cells, less white space (H&E), fibers in non-uniform distribution - Clear predominance of collagen - Dense, regular CT = Long, parallel bundles of collagen fibers in uniform direction - No white space! - Fibroblasts are in longitudinal rows |