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35 Cards in this Set

  • Front
  • Back
Connective tissue types
- 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
CT functions
- Structural - bone/cartilage
- Defense - immune response, ECM thicket
- Transport - nutrients/gasses
- Storage - fat, water, ions
- Repair - wound healing
CT Focus - Changes with age
- Aging compromises all of these functions
Elastosis
- Appearance of wrinkles, bags, sags
Aging effects on CT
- 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
CT degradation factors
- Age - degradation acclerates with age
- Genetics - some faster than others - # stem cells, length of telomeres
- Lifestyle - smoking, sunlight, diet, exercise
- Disease - impacts variable CTs
Layers of skin
- 3 layers
- Epidermis
- Dermis
- Subcutaneous layer (fat, etc.)
Dermis contents
- 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
Ground substance
- 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
Glycosaminoglycan (GAG) disaccharide units
- 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
Core proteins
- 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
Proteoglycan aggregate
- GAG disaccharide units -> GAG's
- Core protein covelently bound to GAG's -> proteoglycans
- HABR binds hyaluronic acid via link protein -> proteoglycan aggregate
Structural multiadhesive glycoproteins
- Laminin and Fibronectin
- Laminin = only found in basement membrane!
- Fibronectin = in dermis (ground substance) - dimer - multiple binding sites
- imparts structural integrity to CT proper
Integrin receptors
- Single-pass membrane proteins - bind to ECM
- 2-way signalling to/from ECM via these
- Can bind cells, collagens, GAGs, proteoglycans, other glycoproteins
Collagen
- 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)
Collagen organization
- Tropocollagen = combination of 3 collagen helices
- Fibril - bundle of tropocollagen molecules
- Fiber - bundle of fibrils
- Spontaneously assembles outside of cell
Collagen synthesis
- 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
Collagen staining with heavy metals (Pb)
- Very distinctive striations!
Fibrillar collagens
- 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
Network collagens
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)
Goodpasture syndrome
- Autoimmune disease attacking Type IV collagen
- Cough blood, blood in urine
- Treatment - immunosuppresive drugs, corticosteroids
Ehlers-Danlos Disorders
- Resulting from defects in collagen or collagen-producing cells
Ehlers-Danlos Type IV
- Mutation in Type III collagen - autosomal dominant
- Strange-shaped face, bulging eyes, translucent skin
- Easy bruising, small and major vessels rupture
Reticular fibers
- 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)
Elastic fibers
- 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
Cutis laxa
- Extremely rare genetic disorder affecting elastic fiber production
- Saggy, inelastic skin
- Other tissues affected also (heart, vessels, joints, lungs, etc.)
Wrinkle histology
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
Experiment with filler injections in old people butts
- Fibroblasts, CT = very sensitive to pressure
- When injected with GAG filler - fibroblasts put out more, higher-quality collagens and elastins
CT cell lineage
- CT cells come from undifferentiated mesenchymal cells
- These give rise to osteoblasts, fibroblasts, adipocytes, etc.
- Wispy cytoplasm, prominent nuclei
Fibroblasts
- 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"...
Adipocytes
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
CT & wound healing
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
Mast cells
- Contain basophilic granules, often found in breast tissue
- heparin, histamines, inflammatory cytokines
Plasma cells
- Make immunoglobins
- ID by "clock-face" nuclei
- Has extensive ER - can see this b/c cytoplasm will be basophilic
Distinguish between loose/dense CT
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