Connective tissue (general) Flashcards
Classifications of CT
- PROPER CT: either loose or dense (depdnding on size of collagen fibers)
- SUPPORTIVE CT: either bone or cartilage (contain viscous, specialised ECM for their mechanical properties)
- SPECIAL CT: either adipose tissue or blood/lymphoid
General functions of CT (6)
- connects tissues for functional and structural integration
- acts as a medium for diffusion and material exchange
- trophic functions
- protects delicate organs
- defense function
- repares tissue damage (scar formation)
General overview of CT proper composition
CELLS:
- Resident cells (formed in CT)
- Migrating cells (formed in other tissue and then migrate into CT)
ECM:
- Fibrillary components (collagen, reticular and elastic fibres)
- Ground substance (H20, glycoproteins, GAGs)
Characteristics of loose proper CT
LOOSE:
-contains less fibers than ground substance
-thin and sparse collagen
-important in the difussion of O2/nutrients/CO2/ waste into and out of blood vessels
-primarily located beneath epithelia
Classificatiosn and characteristics of dense proper CT
DENSE IRREGULAR:
-contains more fibers than ground substance
-contains mainly fibroblasts in terms of cellular components
-abundant collagen arranged in bundles of random orientation
-provides strength
-located in the dermis (in the reticular layer) AND submucosa of hollow organs –> both provide resistance to stretching forces
DENSE REGULAR:
-more fibers than ground substance
-collagen fibers arranged in parallel array and densely packed
-main component of tendons/ligaments.
!! CONTAIN COLLAGEN TYPE ONE
Structure of tendons
-type of dense regular CT
-cord like structures
-attach muscle to bone
-parallel arrangement of collagen fibres
-between fibers are TENDINOCYTES (fibroblasts)
-tendon surrounded by the epitendineum
!!! tendinocytes apper as rows of basophilic nuclei
Collagen levels of organisation of he polymer
- alpha chains (rich in amino acid residues, one in each three chains is glycine, and there is hydroxyproline and proline)
- Tropocollagen: 3 alpha chains wrapped in a helical chain
- Microfibrils: stragerred molecules of tropocollagen joined with covalent cross links
- Fibrils: bundles of microfibrils
- Collagen Fiber: bundles of fibrils
What is collagen periodicity?
Gaps created due to stagerred arrangement of tropocollagen molecules where electrons can pass through in a TEM. Creates alternating electron dense vs light regions
1 Gap = approx 68nm
Collagen synthesis process (7 steps)
INTRACELLULAR PHASE:
1. Protein synthesis of alpha chains on ribosomes of RER (since the protein is secretory)
2. Hydroxylation of lysine in the RER (allows formation of cross links later)
3. Glycosylation starting in RER and completed in Golgi
4. Procollagen is formed (triple helix)
5. Secretion of procollagen via trans Golgi out of cell
EXTRACELLULAR PHASE:
- Cutting of the procollagen globular domain to obtain tropocollagen
- Self assembly of tropocollagen into microfibrils and fibrils into fibers
Collagen maturation definition
-The formation of covalent bonds between tropocollagen molecules when they stagger to form a microfibril
-Prevents degradation of collagen and increases strength
!!! This can only happen if there has been hydroxylation of lysine residues in the RER during collagen synthesis
Overview of the types of collagen (we need to know)
TYPE 1: found in CT of bone, tendon, skin, ligaments, dentin,organ capsules -> provied resistance
TYPE 2: found in Cartilage (hyaline/fibro/elastic), intervertebral discs -> provides resistance
TYPE 3: found in loose CT (organ linings), skin, muscle, blood vessels -> forms reticular fibres to provide scaffolding
TYPE 4: forms basal lamina of ET -> provides support and aids attachment between ET and CT
What are collagen crimps?
-Wavey pattern of arrangement of collagen fibres in tendons and ligaments
Collagen Turnover definition
Dynamic control of the amount of collagen present in each cell by keeping the ratio of collagen synthesis: degradation at an equilibrium
!! all cells have a fixed amount of collagen but not all cells have the SAME fixed amount of collagen
Collagen Turnover process
- Cell receives stimulating factors like growth factors/cytokines
- Release of inactive pro MMPs (matrix metalloproteinases)
- Activation of MMPs via enzymatic cleavage
- Promotes degradation of the ECM
- TIMPs (Tissue inhibitor of metalloproteinase) which block the activation and action of MMPs –> these allow the rate of ECM degradation to be decreased if it gets too high
What determines the classification of type of collagen?
Depends on the specific amino acids of the alpha chain subunits present
what are MMPs?
Matrix metalloproteins: ECM enzymes that degrade collagen
! most important in collagen type 1 cleavage is MMP1
Pathologies associated to faulty collagen turnover (dude to dynamic imbalance)
- EHLERS-DANLOS SYNDROME: causes hyperelasticity of the skin (due to faulty lysyl hydroxylase which prevents cross links from forming due to no hydroxylation)
- OSTEOGENESIS IMPERFECTA: fragile bones due to inability to produce normal Collagen type 1
Reticular fibers structure
-made of collagen type 3
-fibrils are smaller and thinner than collagen 1
-branch out into mesh like networks
-stil exhibit 68nm periodism
-not as efficient in resisting mechanical stress
-play a scaffolding role due to its mesh network
-located in boundary between ET and CT (loose)
What type of staining can be used for reticular fibres (2)?
- PAS: stains well due to the larger concentration of sugar groups presnt
- Silver: argyrophylic, stained black
Elastic fibers structure and location
-thinner and less densely packaged than collagen
-can be ararnged in parallel formations called laminae (in blood vessels) or random arrangements (dermis)
2 components: CORE (made of elastin protein) and SURFACE (made of fibrilin microfilaments)
location: in organs that undergo dilation (bcos of stretching ability): blood vessels, lungs, urinary bladder, skin, ligaments
What stains can be used to visualise elastic fibers?
- orcein red
- Verhoeff stain
- toludeine blue
Elastogenesis process
- INTRACEULLAR STEP:
-synthesis of fibrillin occurs first
-deposition of tropoelastin molecules onto fibrillin
-clumping together and polymerisation of the tropoelastin into elastin (cross linked by lysyl oxidase)
- EXTRACELLULAR STEP:
-aggregation of the inner elastin core and outer fibrillin surface to form the final elastic fiber
Role and structure of GAGs in the ECM
-present in the ground substance
-responsible for physical properties
-long chain unbranched polysaccharides composed of repeating disaccharide units
Differences between hyaluronan GAG and other
-HA is a longer molecule
-can hold a large volume of water
-Not produced in the Golgi, it is formed by enzymes on the plasma membrane
-does not contain sulfate
-Present in the cytoplasm as a free carbohydrate chain
Structure and function of proteoglycan
-GAG connected to a protoglycan core protein (that is negatively charged)
-multiple of these units are connected to a hyaluronic acid molecule via linker proteins
-interacts with collagen fibres and H2O to form complexes surrounded by amorphous tissue
FUNCTIONS:
-resistance to compressive forces
-communication between cells and complexes
-controls turnover rate of fibers
3 types of GAGs and localisation
- Hyaluronan: synovial fluid, ECM ground substances, vitreous fluid
- Chondroitin sulfate: Cartilage/bone/heart valves
- Keratan sulfate: Cartilage/bone/cornea
Role of the ECM
-Provides mechanical and structural suport
-Influecnes extracellular communication
What are the proteoglycans present in ground tissue
- Aggrecans (cartilage)
- Decorin (fibroblasts, cartilage, bone)
- Versican (Fibroblasts)
Multiadhesive glycoproteins present in ground substance (3)
- Fibronectin: contains multiple domains to bind onto collagen/cells –> this maintains CT structure and interaction with ECM components
- Laminin: also contain collagen binding domains, able to bind to collagen type 4 (forms basement membrane)
- SPARC (osteonectin): Modulates GFs and control cell cycle. Regulation of CT homeostasis and its expression increases during cell remodelling
Function of multiadhesive glyproteins (3)
- Stabilise ECM by linking it to its surface
- Possess binding sites for ECM proteins (collagens, proteoglycans)
- Interact with cell receptors
Resident (5) vs migrating cells (3) of proper CT:
RESIDENT
1. Fibroblasts
2. Fibrocytes
3. Macrophages
4. Adipocytes
5. Adult stem cells
MIGRATING
1. lymphocytes
2. Plasma cells
3. Mastocytes/Mast cells
Fibroblasts vs Fibrocytes
FIBROBLASTS: active form of cells, synthesise collagen/elastic/reticular fibres, spindle shaped and elongated, visible basophilic nucleus, abundant RER/Golgi
FIBROCYTE: inactive form of the cell, smaller and less euchromatic nucleus, not much RER
Macrophages in CT description
!! also called HISTIOCYTES
-derived from monocyte maturation
-cytoplasm is abundant in lysosomes
-role in phagocytosis of cell debris/ECM components
-antigen presentation for immune system circulation
!! inactive: bound to collagen
active: dettached from collagen and become more rounded
Adipocytes in CT description
-Large liposome in cytoplasm (causes the displacement of nucleus and thin cytoplasm peripherally)
ROLE: energy storage due to liposome
Leukocyte cells of the proper CT
-transient/migrating cells
-either granulocytes (contain granules and an irregular nucleus) OR agranulocytes (no granules and have a regular nucleus)
-Move to CT via blood vessels –> diapedesis
DIAPEDESIS: formation of pseudopodal peotrusions in between the endothelial cells of capillaries for the cells to migrate. This is done via polymerisation of actin filaments (cytoskeleton) for cell motility
Mast cells in the proper CT
-Transient cell
-arise from bone marrow, enter CT and differentiate into mast cells in the CT
-Contain intensily stained granules in the cytoplasm
-Release of histamine for inflammatory responses, and heparin for anticoagulation
Plasma Cells in proper CT
-transient/migrating cells
-derived from differentiation of B cells
-release of antibodies
-contains cartwheel nuclear morphology (heterochromatin extending from center)
-well developed RER for immunoglobulin production
Histiocyte definiton
Specialised macrophage populations that are specific to certain cell types:
Kuppfer cells: liver
Red pulp macrophages: spleen
Dust cells: alveolar lung
Osteoclasts: bone
Microglial cells: CNS
Further classifications of loose CT
- Mucous (Wharton’s jelly)
- Reticular
- Areolar
Characteristics of mucous loose CT
-loose, amorphous, jelly-like.
-located in the umbilical cord, dental pulp, aqueous humour of the eye
Characteristics of areolar loose CT
UBIQUITOUS
-abundant in cells instead of densely packed fibres
-located within wall of hollow organs (tunica mucosa and submucosa)
-located in tunica intima and adventitia of blood vessels
-forms longitudinal sections in muscles/ tendons/nerves
-surrounds muscle fibers as the endomysium/perimysium and surrounds nerve fibers as the epineurium /perineurium.
What types of connectiev tissue are present in the dermis?
-mainly made up of dense CT
-dermal papillae that come close to the epithelial tissue are loose CT
What type of CT is found on the joints?
-covered by articular cartilage
-synovial membrane: loose CT, makes up the wall of the cavity in which synovial fluid is stored
Characteristics of reticular loose CT
-mainly made up of reticular fibers (interlacing to form networks)
-located in the blood vessels/lymph, spleen, liver
STAIN: need silver staining to pick up the reticular fibers (in black)
General funtions of Loose CT (2)
- Nutrient diffusion between CT and other tissue types (ET).
- Some cells are used in the immune response
5 types of dense CT arrangement + examples and location of each
- Regular parallel (tendons/ligaments)
- Regular orthogonal (cornea, aponeurosis)
- Irregular interwoven (random orientation in the dermis)
- Irregular capsular (external capsuels of organs)
- Lamellar (forms pacinian corpuscles - sensory receptors)
What are the anatomical layers of a hollow organ (from most to least superficial)
- Adventitia (loose CT) or serosa (thin squamous ET)
- Muscularis externa
- Submucosa (loose CT and the location of certain glands)
- Tunica mucosa (ET and underlying loose CT) –> this makes up the lamina propria
- LUMEN