Connective Tissue
Describe mesenchymal stem cells.
multipotent stromal cells that differentiate into a variety of cells.
List the types of specialized connective tissues
- Adipose tissue: white and brown - Blood - Cartilage - Bone
Describe the structure and function of Proteoglycans, and describe some different types of proteoglycan.
- GAGs bound to protein core Aggregate formed by: - Axial hyaluronan molecule - Core proteins attached to core by linker protein - Glycosaminoglycans attached to core protein Types: Versican: all same proteoglycans Aggrecan: 200+ types on one Syndecan: 2 types
Describe macrophages.
- Start as monocytes, move to CT then become macrophages (Histiocyte, or mononuclear phagocyte) - Different names based on location: ○ Liver (Kupffer cells) ○ brain (microglia) ○ Skin (??) ○ bone (osteoclast) - Pseudopodia (legs) - Phagocytes - Produce cytokines (starting upregulation of immune system) - Present antigens via MHC to immune cells - Many lysosomes (black in EM) and phagosomes (white in EM) - Irregular nucleus - Fuse to make large multinucleated Langhan's cells with nuclei in horseshoe or Giant Cells with nuclei in middle(foreign bodies)
13. Identify and describe the cell types responsible for the production of ground substance.
Fibroblasts synthesize the ground substance.
List the three types of Connective tissue proper.
- Loose connective tissue - Dense irregular connective tissue - Dense regular connective tissue
Describe lymphocytes.
- Small and spherical, not much cytoplasm - Condensed, basophilic (dark staining) - B/T cells - B lymphocytes become plasma cells
1. List the three basic components of connective tissue.
1. Cells 2. Extracellular matrix (ECM) 3. Tissue fluid
28. Define the term "lipoma".
A benign tumor composed of adipose tissue.
20. Compare and contrast white and brown adipose tissue in relation to its appearance, location and function.
Adipose cells (adipocyte) Unilocular: one large fat droplet, or white fat - Typical fat cell - Organelles push to side - The triglycerides are a major source of energy - Rich blood supply - Can only be stained with osmium or oil red O Multilocular: brown fat - Many droplets - Central nuclei - Many mitochondria - Also vascular - Innervated - Cytochrome oxidase - Function to make heat (localized to neck, abdomen of neonates)
6. Describe the term "argyrophillic" in relation to staining property, in reticular fibers.
Argyrophilic means silver staining Reticular fibers are argyrophilic
Describe Basophils.
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Describe Neutrophils
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What are the functions of connective tissue?
Connective tissue function: - Support - Repair - Defense (immune) - Nutrition (storage/transport) CT is directly supplied by blood/lymph/nerves
Describe Mast Cells.
FURBALLS! Mast cells - Start in bone marrow, no granules - Migrate to CT and make granules - Same progenitor as basophils - Mast cells are metachromatic - On EM show up with black granules of histamine and heparin - Function to release vasoactive mediators, and chemotactic mediators which attract monocytes, neutrophils and eosinophils to help - Also leukotrienes (vasoactive but not in granules) (delayed reaction)
10. List 2 examples of sites where type l, type ll and type lll collagen and elastic fibers are predominantly found.
Type I (provide tensile strength) - Bone - Tendon - Dentin - Skin Type II - Hyaline and elastic cartilage - Observed as fibrils - Trachea Type III - Reticular lamina of basement membrane (reticular fibers, as in net like arrangement) - Gut, uterus - Tissues that need volume expansion, like liver and spleen Type IV Basal lamina (do not confuse with basement membrane) Binds to binding site of laminin Type V Amnion and chorion in fetus, muscle and tendon sheaths Not banded fibrils
Describe the different types of proteoglycans and their functions.
- Aggrecan: - Description: 100-150 keratan sulfate and chondroitin sulfate GAG chains - Location: Cartilage, chondrocytes - Function: Hydrate ECM of cartilage - Decorin: - Description: small protein, contain only 1 chondroitin sulfate or dermatan sulfate chain - Location: connective tissue, fibroblast, cartilage, bone - Function: helps to orient and assemble collagen - Versican: - Description: 12-15 chains of chondroitin sulfate - Locations: fibroblasts, skin, smooth muscle, brain, and mesangial cells of kidney - Function: participates in cell-to-cell and cell-to-matrix interactions - Syndecan - Description: contains at least 4 types of transmembrane proteoglycans, containing heparan sulfate and chondroitin sulfate - Location: embrionic epithelia, mesenchymal cells, developing lymphatic tissue cells, lymphocyte and plasma cells - Function: the extracellular domain binds collagens, heparin and fibronectin, intraceullar domain binds to cytoskeleton
Generally describe Elastic Connective Tissue.
- Elastic fibers, yellow in color - Ligamentum nuchae, vocal ligament, suspensory ligament of the penis, aorta
Describe Eosinophils.
- Eosinophilic granules - Dense, bilobed nucleus - Phagocytose antibody-antigen complex - Kill parasitic worms
Describe dense regular connective tissue.
- Fibers parallel for tensile strength - Tendon, ligament, aponeurosis - Endotendineum: connective tissue covering around each cell - Peritendineum: covering around a group (fascicle) - Epitendineum: Covering an entire tendon
List the components of ground substance:
- GAGs - Proteoglycans - glycoproteins
14. State a minimum of 3 functions of ground substance.
- Glue to hold cells to fibers - Lubricant for ease of motion and cell migration - Barrier to invaders - Tissue strength
Describe the different types of Glycosaminoglycans and their functions.
- Hyaluronan: synovial fluid, vitreous humor, ECM of CT; great shock absorber - Chondroitin-sulphates: cartilage, bone, heart valves; important in aggrecans, confers shock absorption to articular cartilage - Heparan sulphate: basal lamina, cell surfaces; important for interactions with fibroblast growth factor and its receptor - Keratan sulphate: bone, cartilage, cornea; important in cell motility, cell recognition of protein ligands
Describe dense irregular connective tissue.
- Irregular fibers to withstand stress in many directions - [reticular] Dermis of skin, capsule of organs, submucosa of GI, periosteum (layer covering bones) - Fewer cells, more fibers - Fibers appear arranged in no particular direction
Describe the different types of glycoproteins and their functions.
- Laminin: in basement membrane, hemidesmosome, attach - Fibronectin - chondronectin
Describe collagen in general.
- Long protein polymer - Most abundant protein (30% of total) - Types: (90% is type 1) ○ Fibril forming: type 1 ○ Fibril associated: ??? ○ Network forming: type 3, forming a net ○ Anchoring types: hold things to other things - Acidophilic (pink) - Glycine (~30%), proline, hydroxyproline, hydroxylysine - Procollagen formed intracellular, collagen assembled extracellular
18. Define the term "lamina propria".
- Loose connective tissue of the mucous membrane - Below basement membrane
Describe fibroblasts.
- Most common cell in CT - Synthesize fibers and ground substance - Spindle shaped - Active (basophilic cytoplasm/fibroblast) or inactive (fibrocytes) - Example: myofibroblast heal wounds
Describe the structure and function of glycoproteins.
- Multi-adhesive glycoproteins (MAGs): paste cells to fibers and whatever else - Adhesion molecules: Fibronectin, laminin, chondronectin - Integrins (RGD sequence), like glue: cell surface receptor to bind cell to matrix
Generally describe reticular tissue.
- Reticular fibers are covered by cytoplasmic extensions - Framework for myeloid (bone marrow) and lymphoid (lymph nodes, spleen) organs
Describe loose connective tissue.
- Space filler (like space between epithelium and cartilage) - Lots of cells, less fibers - Flexible, rich blood supply - Does not resist stress - Areas of high metabolic activity (to allow oxygen/nutrients to diffuse)
Describe Reticular fibers.
- Type III collagen primarily - short, thin and branching - Locations: ○ To support loose cells (like spleen, lymph etc) ○ That might expand (wall of GI, arteries, testes) - Properties: ○ argyrophilic/silver staining ○ PAS positive (due to carb content) - First type of collagen made in wound healing
Describe the structure and function of Glycosaminoglycans (GAGs).
- the tiniest bristles - GAGs bound to protein core = proteoglycans monomer - many proteoglycan monomers attached to hyaluronan molecules is proteoglycan aggregate - Types of GAGs: Dermatan sulfate, chondroitin sulfate, keratan sulfate, heparan sulfate
Highlight key features of a fibroblast under TEM.
Active protein synthesis by cell - Extensive RER and golgi - Euchromatic nucleus - Collagen fibers visible outside of cell
25. Explain the alteration in collagen synthesis due to deficiency of ascorbic acid, in scurvy.
Ascorbic acid/vitamin C is needed by prolyl and lysyl hydroxylase in the formation of collagen. Hydroxyproline help to form H-bonds between the triple helix, stabilizing its structure Hydroxylysines are necessary for the addition of glycoproteins. Connective tissue degeneration leads to bleeding gums, poor wound healing, hemorrhaging.
26. Explain the connective tissue cell involvement in anaphylactic shock involving release of histamine and heparin.
Basophils are found in blood (specialized connective tissue). Mast cells are found in connective tissue proper. Basophils and mast cells release histamine and heparin upon stimulation. Histamine is a vasodilator and bronchiole constrictor. Heparin is an anticoagulant.
3. Identify and describe the cell types responsible for the production of collagen, elastic and reticular fibers.
Collagen: Fibroblast Osteoblast (synthesize bone) Chondroblast (cartilage cells) Odontoblast (make dentin, layer below enamel) Reticular fibers: Reticular cells (modified fibroblasts) Reticular fibers are covered by cytoplasmic extensions Elastic: Fibroblast Smooth muscle cell
What is connective tissue?
Connective tissue: lots of loosely packed cells with wide intercellular spaces and extracellular matrix. - Connective tissue is stroma (bed covering, or sheet, that covers parenchyma) - it's developed from mesoderm - It's an interface/barrier between different tissue types
7. Describe the formation of collage fibers.
Describe the formation of collagen: Made in fibroblast, odontoblast, chondroblast, osteoblast 1) RER: synth of precollagen and procollagen 2) RER: hydroxylation of lysine/proline, glycosylation, disulfide bonds 3) Golgi: packaging, secretion of procollagen 4) Removal of nonhelical domain to make tropocollagen 5) Side-by-side cross-linking of collagen fibrils into collagen fibers Vitamin C important for hydroxylation and final product
5. Describe the basic components of extracellular matrix.
Fibers: - Collagen (of various types) - Reticular fibers (type II collagen) - Elastic fibers Ground substance: - GAGs (glycosaminoglycans) - Glycoproteins - Proteoglycans Tissue fluid
Describe Elastic fibers.
Fibrillin (glycoprotein) interwoven with elastin (protein) Relaxed in random coil, stretched and re-relaxes to different coil Elastin - glycine, proline, desmosine and isodesmosine (lysine-like) Very elastic - 5X more than rubber Large arteries, elastic cartilage, vocal ligament, bronchi etc
23. Describe the changes in the elastic fibers that may lead to some of the clinical features of Marfan's syndrome.
Fibrillin-1 is a major component of microfibrils, which form a sheat around amorphous elastin If Fibrillin-1 missing, elastic CT is dysfunctional Mutation in fibrillin gene (FBN1) causes Marfan's syndrome The absence of microfibrils during elastogenesis results in the formation of elastin sheets or lamellae. This leads to, among other things, abnormally elastic tissue. Patients are lanky, above average height, with possible scoliosis/kyphosis. (probably due to inability of mutated fibrillin to properly sequester a reservoir of transforming growth factor beta (TFG-beta) Pts susceptible to aortic aneurism because aorta loses elasticity
22. Describe the physical abnormalities seen in Ehler Danlos syndrome, due to genetic defect in collagen fiber synthesis.
Heriditary defect in collagen: - Abnormal collagen renders structures more elastic Symptoms: - Hypermobility of joints - Pale thin skin, with hyperelasticity - Early death from rupture of vessels/internal organs
24. Explain the abnormality in the collagen fiber synthesis leading to formation of keloid.
Keloid scar is an overgrowth of scar tissue following injury beyond the borders of the injury. In normal wound healing, myofibroblast (differentiated fibroblasts) heal the wound and then undergo cell death, leaving a connective scar with few cellular elements. In keloid scars, myofibroblasts do not undergo cell death and continue making scar tissue.
11. State the major component of basal lamina.
Laminin (a glycoprotein) Basal lamina: Lamina rara/lucida Lamina densa Basement membrane (not a membrane, but a matrix) Basal lamina + lamina reticularis
Describe Embryonic connective tissue.
Mesenchyme: - type of embryonic connective tissue - In developing fetus - Small stellate (star-like) fibroblasts, connecting to each other - Gap junction communication - Very little fibers (less resistance to growing fetus) Mucous connective tissue: - type of embryonic connective tissue - Few cells/fibers, mostly ground substance - Jelly-like, Wharton's jelly, mucoid nature, holds onto water, lots of GAGs, hyalanuric acid - Found in: Cardiac jelly, vitreous humor in eye, umbilical cord - Maintain open vessels even when loose knots form in umbilical cord
27. List the component of connective tissue involved in the process of edema.
Myxedema is caused by connective tissues retaining more water than normal in the ECM. GAGs and other ground substances hold more water and expand the tissue. Histamine, produced by basophils and mast cells, also leads to edema by making blood vessels leaky.
9. List 2 stains used in staining elastic fibers.
Orcein Resorcin-fuchsin Verhoeff's
12. State the stains used to identify connective tissue in light microscopy.
PAS: - used to stain glycoproteins and proteoglycans in the basement membrane Silver Stain: - Reticular fibers Osmium/Red Oil O: - Fat (adipocytes) Elastic fibers: - Orcein - Resorcin-fuchsin - Verhoeff's
Which CT cells are permanent resident of CT and which cells are transients?
Permanent residents of CT: - Fibroblasts - Adipose cells - Macrophages - Mast cells - Mesenchymal stem cell Transient cell - Lymphocytes - Plasma cells - Eosinophils - Basophils - neutrophils
4. Define "metachromasia" and describe the function of mast cell that exhibits this property.
The cells take on a color other than the dye Cells that have concentration of ionized sulfate and phosphate groups (heparin containing granules)
Describe the formation of elastic fibers:
Three developmental stages: 1) Oxytalan 2) Elaunin 3) Elastic fibers Formation: 1) RER: synth of elastin three components: proelastin (containing desmosine and isodesmosine), microfibril-associated glycoprotein (MAGP), and fibrillin 1 & 2 2) Golgi: packaging/secretion of elastin precursor 3) Extracellular: assembly of tropoelastin and MAGP to immature elastic fibers (MAGP connects parallel fibers) 4) Extracellular: mature fibers bundled
Describe the two types of adipose cells (adipocytes).
Unilocular: white fat - Typical fat cell - one large fat droplet - Organelles push to side (making a signet ring) - The triglycerides are a major source of energy - Rich blood supply - Can only be stained with osmium or oil red O Multilocular: brown fat - Many droplets around Central nuclei - Many mitochondria, Cytochrome oxidase - Highly vascularized and innervated - Function to make heat (localized to neck, abdomen of neonates)
8. State the co factor necessary for the synthesis of collagen fibers.
Vitamin C (ascorbate): - Required for hydroxylation of lysine/proline - Final structure depends on the hydroxylation - Vit C deficiency delays/prevents wound healing