Bone and Muscle Physiology Flashcards
What 2 things is connective tissues made from?
Cells
Extracellular matrix
What 2 things is extracellular matrix formed of?
Give properties of each
Fibrous proteins
- collagen
- elastin
Ground substances
- transparent
- colourless
What 3 things is ground substance formed from?
Give properties of each
Proteoglycans
- repeated disaccharides (GAG) around a protein core
- GAG attracts water
Glycoproteins
-allow cells to adhere to the ECM
Water
-attracted by GAG
What provides the rigidity of bones?
Mineralised extracellular matrix (hydroxyapatite)
What provides the resilience of bones?
Type 1 collagen fibres
part of the fibrous proteins component of ECM, other component is ground substance remember
What is the condition caused by too little bone called?
Osteoporosis
What is the condition caused by too much bone called?
Osteopetrosis
What is osteoporosis?
A complex skeletal disease characterised by low bone density and micro-archeitectural defects in bone tissue, resulting in increased bone fragility and susceptibility to fracture.
Name 5 wider implications of osteoporosis
Future #
Pain
QOL
Long term admission
Mortality
Describe the general pathophysiology of osteoporosis
Menopause decreases oestrogen levels
Aging decreases replication of osteoprogenitor cells - fewer osteoblasts being made
Aging decreases activity of remaining osteoblasts - less new bone being made
Increases expression of RANKL and RANK on osteoclasts - favours bone re absorption
What scan is used to assess bone mineral density?
DEXA scan
What would a normal T score on a DEXA scan be?
T score _> 1
What would an osteopenia T score on a DEXA scan be?
T score less than -1 but above 2.5
What would a osteoporosis T score on a DEXA scan be?
T score <2.5
What is first line management according to NICE in osteoporosis?
Bisphosphonates
Name the 2 bisphosphonates on the drugs list
Alendronic acid (alendronate)
Resedronate
What is the MOA for bisphosphonates?
Bisphosphonates attach to hydroxyapatite binding sites on bony surfaces, especially surfaces undergoing active resorption.
When osteoclasts begin to reabsorb bone that is impregnated with bisphosphonate, the bisphosphonate released during reabsorption impairs the ability of the osteoclasts to form the ruffled border, to adhere to the bony surface, and to produce the protons necessary for continued bone resorption
How does alendronic acid have to be taken?
First thing in the morning, half an hour before food, glass of water, sit upright for half an hour
What are the side effects of bisphosphonates?
Asymptomatic hypocalcaemia
GI disturbances
Oesophageal reactions (sit upright)
Osteonecrosis of the jaw (larger doses)
What class of drugs is given is bisphosphantes are not tolerated?
Name the drug
Selective estrogen receptor modulators
Raloxifene
Does not stimulate breast or uterine tissue, less at risk of CA.
What SC injection can be given to treat osteoporosis?
Parathyroid hormone
What is denosumab’s mechanism of action?
How is it given?
It is a monoclonal antibody
Acts in a similar way to OPG
Mops up excess RANKL, reduced activation of osteoclasts
Inhibits osteoclast formation, function, survival.
SC injection once every 6 months
Rickets and osteomalacia are characterised by…..
What is the most common cause?
inadequate mineralisation of bone
Vitamin D deficiency
Describe Rickets
Defective bone mineralisation at the growth plate only affecting children
Widening of the growth plate
Vitamin D deficiency - chondrocytes fail to apoptose after hypertrophy - growth plate remains soft.
Growth retardation
Bony deformities
Describe osteomalacia
Defective osteoid mineralisation affecting adults and children
What is a lytic lesion?
Parts of the bone that have been destroyed, usually due to secondary malignancies/metastasis e.g. breast and lung CA
What is a schlerotic lesion?
Thickening/hardening of the bone. Stimulation of bone production so the bone is denser
Usually secondary to prostate CA.
Describe Paget’s disease of the bone
Increased bone turnover
Increase in osteoclast activity, which increases osteoblast activity. Increased amount of woven bone being laid down.
Can have focal or multifocal sites.
Results in overgrowth, bowing, pain, fractures and deformity
What investigations would you do to diagnose Paget’s disease of the bone?
Bloods - Ca, PTH (normal), ALK P (high)
X rays
Radionuclide bone scans
Bone biopsy if malignancy is suspected
How do we treat Paget’s disease of the bone?
Walking aids
Analgaesia
Supplements
Bisphosphonates
Surgery
What is osteogenesis Imperfecta?
A group of hereditary disorders characterised by defective production of type 1 collagen.
Type 1 - more prone to #, but unlikely to have deformities from them
Type 2 - brittle bone disease. Bones can break during labour, can have respiratory compromise, likely to die in the first few years.
Which part of the connective tissue determines the tissue’s physical properties?
Extracellular matrix
Name 2 important fibres that can be present in the extracellular matrix
Collagen
Elastin
Where is collagen found?
Type 1 - bone, tendons, ligaments
Type 2 - hyaline cartilage
Type 3 - structural framework of spleen, liver, smooth muscle
Good at resisting tensile forces
Name some properties of elastin
Major component of elastic fibres
Enables stretch and recoil of tissues
Usually mixed with collagen to prevent overstretch
Found in walls of large arteries, lungs, skin
Name 3 characteristics of cartilage
Strong, flexible, semi-rigid
Can withstand compression forces (shock absorber)
Smooth surface enables friction-free movement
Name 3 functions of cartilage
Forms articulating surface of bones
Growth and development bones (endochondral ossification)
Supporting framework of some organs e.g. walls of airways
Name some specialist features of cartilage extracellular matrix
Contains aggrecan - this is a proteoglycan that contains glycosaminoglycans, which are hydrophillic and therefore attract a lot of water to the cartilage
Collagen fibres
Elastin fibres
Name the proteoglycan found in the ECM of cartilage
Aggrecan
A proteoglycan that contains glycosaminoglycans which attract water
What is the layer surrounding cartilage called?
What is special about this outer layer compared to the rest of the cartilage?
Perichondrium
- outer fibrous layer
- inner cellular layer
The perichondrium contains blood vessels: the rest of the cartilage is avascular
Why does cartilage take a long time to heal?
Because it is avascular
Cartilage cells get their nutrients by diffusion from the perichondrium
What do cartilage cells derive from?
Mesenchymal stem cells
Outline the formation of a chondrocyte (cartilage cell)
Mesenchymal stem cells differentiate into chondroblasts (cartilage building cells)
Chondroblasts are found in the inner cellular layer of the perichondrium
Chondroblasts secrete extracellular matrix and get trapped inside lacuna (spaces)
Chondroblasts then mature into chondrocytes
Name the 2 types of growth cartilage can undergo
Appositional
Interstitial
Describe the process of appositional growth of cartilage
Surface layers of matrix added by chondroblasts in perichondrium
Describe the process of interstitial growth of cartilage
Chondrocytes grow and divide and lay down new matrix.
As more matrix is being made, the chondrocytes get pushed away from each other.
Multiple chondrocytes can end up occupying one lacuna and the lacuna will get further away from each other
Happens in childhood and adolescence
Why does cartilage repair badly in adults?
Because most interstitial growth happens in childhood and adolescence
May be some regeneration of damaged cartilage from chondrogeneic cells in the perichondrium
But if the damage is large or the cartilage has been removed from the perichondrium, the defect will be replaced with dense connective tissue
Name the 3 types of cartilage
Hyaline
Fibrocartilage
Elastic
What is the most common and weakest type of cartilage?
Hyaline cartilage
Briefly describe hyaline cartilage
Contains short and dispersed type II collagen fibres and large amounts of proteoglycans
Has a perichondrium layer (except at articular surfaces)
Name 3 places where hyaline cartilage is found
Articular surfaces of joints
Costal cartilages
Epiphyseal growth plates
What is the strongest form of cartilage?
Fibrocartilage
Briefly describe fibrocartilage
Contains thick parallel bundles of type I collagen alternating with hyaline cartilage matrix
No perichondrium
Found in places that need to resist significant forces
- insertion points of ligaments/tendons
- IV discs
- pubic symphisis
Briefly describe elastic cartilage
Strong, flexible, resilient
Structures that require deformation but can regain original shape
Contains elastic fibres and type II collagen fibres
Has a perichondrium
What is a joint?
Where 2 or more bones articulate
Name the 3 types of joints, according to movement, and their characteristics
Synarthrodial joint - fixed no movement
Amphiarthrodial joint - slightly movable
Diarthrodial joint - freely movable
Name the 3 types of joints
Fibrous
Cartilaginous
Synovial
Name the 2 types of fibrous joints
Briefly outline their structure
Sutures
Syndesmoses
Fibrous joints are bones connected by dense connective tissue, containing mainly collagen but no cartilage
Give an example of a suture fibrous joint
What type of movement does this joint undergo?
Flat bones of the skull
Synarthrodial joint - no movement
Give an example of a syndesmoses fibrous joint
What type of movement does this joint undergo?
Interosseous connective tissue membrane connecting long bones
Amphiarthrodial joint - slightly moveable
Briefly describe cartilaginous joints
Bones connected entirely by cartilage
Can be immovable or slightly movable
Primary and secondary cartilaginous joints
Describe a primary cartilaginous joint
Hyaline cartilage only
Found at epiphyseal growth plates and costal cartilages
Describe a secondary cartilaginous joint
Hyaline cartilage lines the bones with fibrocartilage in between
IV discs, pubic symphysis, manubriosternal joint
Describe 3 characteristics of a synovial joint
Prescence of a joint cavity between the bones, which contains synovial fluid
Hyaline cartilage
Joint enclosed by a joint capsule with outer fibrous membrane and inner synovial membrane
Which layer of the joint capsule secretes synovial fluid?
Inner synovial membrane
Describe a bursa
A sac made of synovial membrane containing synovial fluid that reduce friction of one structure moving over another
How are synovial joints reinforced?
Give an example
Fibroelastic ligaments crossing the joint prevent excessive movements
Lateral meniscus of the knee
Name the 6 types of synovial joints
Hinge
Ball and socket
Plane
Saddle
Pivot
Condyloid
Briefly outline osteoarthritis
Most common joint disease
Loss of articular cartilage +/- bone leading to synovitis
List some risk factors for OA
Genetics
Age
Female sex
Trauma
Obesity
High/low bone density
What causes primary OA?
Genetic factors, no precipitating insult
What causes secondary OA?
Joint pathology e.g. trauma, infection, joint defects
Draw out the pathophysiology of OA
See slide 36 of joint disease lecture and footnotes
What 4 pathological changes would you see on an X ray in someone with OA?
Joint space narrowing - asymmetric
Subchondral cysts and sclerosis
Osteophytes
Malalignment
List some signs and symptoms of OA
Joint stiffness
Joint pain
Functional limitation
Rest/night pain
Restricted movement
Crepitus
What are the nodes called on the hands that are visible in OA?
Herberden’s nodes
