Biochem - Connective Tissue Flashcards
Types of connective tissue diseases
Sarcoma
Autoimmune
Congenital
Acquired
Examples of autoimmune connective tissue diseases
RhA
SLE
Examples of congenital connective tissue diseases
OI
Ehlers Danlos syndrome
Marfans
Examples of acquired connective tissue diseases
Scurvy
OA
Tendinitis
Characteristics of connective tissue
Highly specialised Mechanical support, movement Contains blood vessels, nerves Arena for fighting infection Regulates cell behaviour
Connective tissue components
Fibres
‘Ground substance’
Matricelluar proteins
Spp cells
Connective tissue fibres
Collagen
Elastic fibres
‘Ground substance’
Everything except collagen e.g. proteoglycans
Spp cells found in skin, tendons and ligaments
Fibroblasts
Spp cells found in cartilage
Chondrocytes
Spp bones found in bone
Osteocytes (osteoclasts and osteoblasts)
Structure of elastic fibres
Heavily cross linked
Components of elastic fibres
Elastin
Fibrillins (1-3)
Fibulins
Matriculates Associated Glycoproteins (MAGP)
Roles of elastic fibres
Structure
Regulation (growth factor signalling)
Conditions caused by defects in elastin
Cutis laxa
Wiliams syndrome
Supravalvular aortic stenosis
Conditions caused by defect in Fibrillin-1 (fibrillinopathies)
Marfan syndrome
Acromelial dysplasia
Stiff skin syndrome
Progeroid syndrome
What is proteoglycan important for
Connective tissue material properties
Features of proteoglycan
Variable in size
Confer viscoelastic properties
Hold water in tissue
Interact w. cells, cytokines and collagen
Main structural component of connective tissue
Collagen fibrils
Structure of collagen fibrils
3 alpha chains arranged in triple helix secreted into ECM
Each alpha chain is a single gene product
Types of collagen
Type I Type II Type III Type IV Type V
Type I collagen
Approx 90% of the collagen in the body is type I
Main component of bone, dermis, tendons and ligaments
Utilised in wound healing
Type II collagen
Formed of copolymers
Main component of cartilage and is also found in the cornea and vitreous humour
Type III collagen
Found in arteries and hollow organs, often in combination with type I
Also called reticular fibres
Type IV collagen
Forms basement membrane
Type V collagen
Found in cell surfaces, placenta and hair
Helps organise type I collagen in the dermis
EDS is associated with a mutation in which type of collagen
V
Scurvy
Vit C deficiency
Shows importance of collagen hydroxylation
Presentation of scurvy
Bleeding gums Loss of teeth Skin lesions, bruises Poor wound healing Joint pain and weakness
What differs in each type of connective tissue
Collagen composition and organisation
Collagen composition in skin
60% Type I collagen
30% Type II collagen
Organisation of collagen in skin
Meshwork of fibres
Collagen composition in tendon/ligaments
90% Type I collagen
5% Type II collagen
Organisation of collagen in tendon/ligaments
Parallel fibres
Collagen composition in bone
90% Type I
2% Type II
Organisation of collagen in bone
Sheets (lamella)
Collagen composition in cartilage
95% Type II collagen
Organisation of collagen in cartilage
Meshwork of fibres
Structural and biomechanical changes in OA cartilage
Loss of proteoglycans
Collagen ‘fibrillation’
Enzymatic degradation
Common site of tendon pathology
Enthesis/ insertion as it is a region of stress conc
Common syndromes affecting enthesis
Tennis elbow
Golfer’s elbow
Jumpers knee
Osgood-Schlatters
Tendinopathy
A degenerative condn Loss of collagen organisation and reduced fibril diabetes Changes I collagen content Vascular (and nerve) infiltration Failure to repair
What mostly causes OI
Defects in Type I collagen genes
Type I OI
Mildest and most common form
Quantitative defect
Half the amounts of normal type I collagen
Type II OI
Most severe - death in utero
Qualitative defect - missense mutation
Abnormal Type I collagen
EDS types
Classical Benign hyper mobility Vascular Kyphoscoliosis Arthrochalasia Dermatosperaxis
Dx of EDS (& other genetic condns)
Detailed clinical and family hx Physical examination Skin biopsy and histology Biochemical analysis e.g. culture and urine analysis Molecular analysis of spp genes(s)
Treatment of EDS and connective tissue disorders
Vascular damage is most important complication
Control risk factors
Drugs
Controlling risk factors as treatment for connective tissue disorders
Healthy lifestyle
Protection (bandages, splints, padding)
Avoidance of contact sports and heavy exercise
Supplementation of vitamin c
Drugs to treat connective tissue disorders
Beta blockers may reduce aortic dilation
Why should NSAIDs and aspirin be avoided when treating connective tissue disorders
Platelet function and clotting
What is EDS
A rare autosomal ctd that is primarily characterized by skin hyperextensibility, abnormal wound healing/atrophic scars and joint hypermobility. 90% of pts have all criteria listed.
Clinical symptoms of Marfan’s
Scoliosis Chest deformities Arachnodactyly (long fingers) Tall, thin Joint hypermobility Craniofacial abnormalities Cardiovascular defects Ocular defects
Developmental problems of collagen
Chondrodystrophies
Collagenopathies
Structural problems of collagen
OI
EDS
Marfan’s
Condns associated with collagen maintenance and repair
Osteoporosis
OA
Tendinopathy
Ligaments vs tendons
Tendons attach muscle to bone but ligaments attach bone to bone
Function of tendons
Tendons are slightly elastic, allowing to transmit forces from muscle to bone
Function of ligaments
Help stabilise a joint by restricting excess movement and minimising risk of injury
Structure of tendons
Collagen fibril –> subfasicle –> fascicle —> tertiary fibre bundle
Endotenon
Connective tissue separating fascicles
Facilitate gliding of bundles independently against one another during movement
Epitenon
Found outside tertiary fibre bundles
Types of entheses
Fibrocartiliginous
Fibrous
Zones in fibrocartilaginous entheses
Fibrous connective tissue (the tendon)
Uncalcified fibrocartilage
Calcified fibrocartilage
Bone
Sharpey’s fibres
Where calcified fibrocartilage interdigitates with bone
Fibrous entheses
Tendons merge with the periosteum before attaching by fibrous tissue to the bone
