LOCO2 OVERVIEW Flashcards
Osteoclasts
Cell that breaks down the bone - secrete digestive enzymes
How to recognise osteoclast from image
Sits in a depression
LARGE cells
Multinucleated
NB NOT LOCO - where is collagen type III found?
Reticular fibres - supporting network of tissues for e.g. liver, bone marrow
Collagen type found in bone
Collagen I
Components of ECM of bone
Collagen I and proteoglycans
Osteoclast is a relative of which cell type?
Macrophage
Osteoprogenitor cells
Can differentiate into osteblasts
Osteoprogenitor cells - cell type
Mesenchymal cells
Where are osteoprogenitor cells found?
Endosteum
What is the endosteum?
Thin, vascular membrane of connective tissue lining the inner component of the bone
Recognise osteoblast from image
Cuboidal like cell
Sat at the surface of the bone matrix
Recognise osteocyte from image
Little black dots - look like pits
Sat within lacunae (surrounds the black dot)
Types of bone
Lamellar (mature) - have the cortical and the cancellous/spongy/trabecuale
Woven - immature bone
What is found within trabeculae bone?
Bone marrow - important for production of RBCs
Why is woven bone weak?
Mechanically weak due to random organisation of the collage fibres
Laid down very quickly - lack of organisation
Organic vs. inorganic components of bone
35-40% organic ECM - proteoglycans, collagen I, cytokines
60% - inorganic salt - calcium hydroxyapatite
5% - water
Canaliculi - what are they and what cell are they found on?
Little black processes present osteocytes - these sense the surrounding environment for any signs of stress that the surrounding bone may be under
‘Scerostin’
Secreted by happy osteocytes that are under no stress
Prevents production of new bone by osteoblasts
Effect of PTH on sclerostin
PTH - stress hormone released by osteocyte
Inhibits secretion of sclerostin
Induces bone production
RANKL
Ligand that stimulates bone resorption
Produced by osteocytes and osteoblasts
RANK
Receptor for RANK found on osteclasts and precursors
‘Osteoid’
Unmineralised bone matrix
How is osteoid mineralised and when?
By calcium hydroxyapatite - about one week after it is laid down
How long does bone remodelling take from start to finish?
About three months
Normal serum calcium levels
2.2-2.6mmol/L
What is the recommended daily intake of calcium?
500-1300mg
Normal plasma concentration of phosphate
0.8-1.5mmol/L
PTH receptor found on which cell?
Osteoblast
Action of PTH on osteoblast?
Release of RANKL - acts of onsteoclasts
Action of 1,25-dihydroxyvitamin D in calcium regulation
Increases calcium reabsorption from the gut
Calcitonin
Released from thyroid gland when calcium levels are too high (>2.6mmol/L)
‘Osteoporosis’
Reduced bone density due to reduced levels of tissue resulting from calcium or vitamin D deficiency
What does a DEXA scan measure?
Bone density/bone mass
Mechanism of action of bisphosphonates
Drug incorporated into the bone when taken
Taken up into osteoclasts as they break down the bone
Promotes apoptosis of the osteoclasts
Teriparatide
Short term PTH - increases action of osteoblasts - so builds up bone for osteoporosis
NB. PTH activates osteoblasts in short term and osteoclasts in long term
Denozumab
Antibody for osteoporosis treatment
Binds to RANKL to prevent it from binding to osteoclasts - reduces the action of osteoclasts
‘Osteomalacia’
Lack of bone mineralisation due to insufficient levels of vitamin D
Insufficient calcium and phosphate to mineralise the bone
Define pseudofractures
Regions of unmineralised bone (osteoid)
How much sun exposure should an individual have to get sufficient levels of vitamin D?
15 minutes of sun on the hands and face 2-3 times a week
Treatment of osteoporosis
Vitamin D and calcium supplements
HRT for menopausal women
Bisphosphonates
Antibodies
Five foods high in calcium
Bread Leafy green veg Beans and pulses Milk Dried fruit
Osteosarcoma and Paget’s disease
Osteosarcoma is a rare complication of Paget’s - due to the high stage of compensatory proliferation of woven bone
‘Paget’s disease’
Disruption to the cycle of bone renewal and repair
Type a vs. Type b synoviocytes
a
Tissue type of the subintima
a
Composition of synovial fluid
a
Leucocytes present in RA
Lymphocytes - infiltrate the synovial membrane
Neutrophils - enter the synovial fluid
Leucocytes present in RA
Lymphocytes - infiltrate the synovial membrane
Neutrophils - enter the synovial fluid
Components responsible for the viscosity of hyaluronic acid
a
Function of synovial fluid
a
Antibodies produced in RA and their action?
Anti-citrullinated protein antibodies (ACPA)
Stimulates osteoclast differentiation and proliferation
DKK-1 and their actions
Produced by Th17 where there are no osteoclasts - induces production of sclerostin - osteoblasts are switched off
Action of neutrophils in synovial fluid
Respiratory burst - production of free radicals - damage to hyaluronic acid, synovial fluid, subchondral exposed bone, articular cartialge
Action of neutrophils in synovial fluid
Respiratory burst - production of free radicals - damage to hyaluronic acid, synovial fluid, subchondral exposed bone, articular cartialge
Prevalence of RA
1%
RA symmetrical or non-symmetrical?
Symmetrical
Joints affected in the hands in RA?
MCP and PIP joints
First line management for RA
Pain relief - analgesic ladder
First line management for RA
Pain relief - analgesic ladder
Gold standard conventional DMARD
Methotrexate
Mechanism of action of conventional DMARDs
Immune suppressants
Mechanism of action of methotrexate
Folic acid/folate inhibitor - NOT to be used in pregnant women
Targets any proliferating cells - not just the proliferating immune cells SO has systemic effects
How long before methotrexate has an effect?
3-12 weeks
Adverse effects of methotrexate
Hepatic problems - liver failure
Stem cell problems
Direct action of methotrexate
Dihydrofolate synthetase
Indirect action of methotrexate
Thymidate synthetase
Indirect action of methotrexate
Thymidate synthetase
Main site of action of sulfasalazine and why?
a
Metabolite of sulfasalazine and site of action of this
a
Hydroxychloroquine and mechanism of action
Animalarial
Accumulates in lysosomes to reduce pH - reduces protein modifications
Blocks toll-like receptor 9 - reduced activation of dendritic cells
Hydroxychloroquine should be avoided in who?
In patients with psoriatic arthritis - makes their skin condition worse
Patients that cannot take methotrexate should be given what?
Leflunomide
How long for gold to have an effect in the treatment of RA?
4-6 months
Name three biological TNFa blockers
Entanercept
Infliximab
Adalumumab
Name a biological that has an action of B cells nad what is the target?
Rituximab
CD20 on B cells
Name a biological that has an action on T cells and what is the target?
Abatacept
CD28 on T cells
Nerve roots of the femoral nerve
L2, L3, L4
Nerve roots of the obturator nerve
L2, L3, L4
Nerve roots of the sciatic nerve
L5, S1, S2
Order of nerves in the lumbar plexus
Subcostal Iliohypogastric Ilioinguinal Genitofemoral Lateral cutaneous Obturator Femoral
Nerve roots of the lumbar plexus
L1-L4
Borders of femoral triangle
Inguinal ligament
Sartorius
Adductor longus
Three bones involved in the ankle joint
Tibia
Fibula
Tallus
Name of heel bone
Calcaneus
On which side of the arm are the cephalic and basilic veins located?
Cephalic - radial side
Basilic - ulnar side
Muscles responsible for abduction of the arm
Supraspinatous - first ten degrees
Deltoid - rest of the movement
Nerve roots of the brachial plexus
C5-T1
Two nerves that can cause winging of the scapula and what do these innervate?
Long thoracic nerve - serratous anterior
Spinal accessory nerve - trapezius
Presentation of radial nerve damage
Wrist drop
Presentation of median nerve damage
Hand of bennidiction
Define osteoid
Unmineralised organic component of bone
Presentation of Duputren’s contracture vs. trigger finger
Trigger finger closer to the palm of the hand
Dupuytren’s contracture is common in who?
Men Heavy drinkers Diabetes Smokers Classically: HEAVY DRINKERS
What is Dupuytren’s contracture?
Palmar aponeurosis
Protein involved in genetic aspect of OA
HMGB2 - early onset OA
Chondromalacia and how does this occur in OA?
Softening cartilage
Lack of proteoglycans
Increased water moves into the collagen and causes chondromalacia
NB. water than moves out again due to lack of proteoglycans to hold the water in place
What happens following chondromalacia of the cartilage
Chondromalacia followed by fibrilation (and then erosion and cracking and then eburnation)
Collagen type found in bone
Collagen type I
Collagen type found in articular hyaline cartilage of synovial joint?
Mainly collagen type II
Deeper radial layer - collagen type X
Main proteoglycan in the body?
Aggrecan
Function of proteoglycans in articular cartilage?
Negative side chains - attracts water from the synovial fluid
OA bilateral or unilateral and why?
OA can be either - starts of as unilateral - person uses joints on the other side of the body to compensate for their weakening joints - becomes bilateral
OA or RA more common?
OA
Age of onset OA vs. RA
OA - rare prior to 45 years
RA - peak age of onset between 20 and 40 years
Almost everyone develops OA or RA?
OA
Morning joint stiffness presentation in OA
Tender and aching joints - don’t tend to be that swollen
Morning stiffness lasting less than one hour
Stiffness returns at the end of the day/after periods of activity
Morning joint stiffness presentation in RA
Very stiff, swollen, inflamed joints
Morning stiffness lasting more than one hour
Due to lack of movement in the night and formation of gel in the synovial fluid
Systemic symptoms of OA vs. RA
OA - no systemic symptoms
RA - feeling ill and fatigue
Heberden’s vs. Bouchard’s nodes
Both are osteophyte formation in OA
Bouchard’s - PIP
Heberden’s - DIP
Four signs of OA on x-ray
Loss of joint space
Osteophyte formation
Subchondral sclerosis
Trabeculae fractures
Effect of IL17 on synovial macrophages
IL17 causes a switch in the phenotype of synovial macrophages to osteotype macrophages
Primary curves
Kyphoses - thoracic and sacral
Secondary curves
Lordoses - lumbar and cervical
Increased thoracic kyphoses - three causes
Osteoporosis
Erosion
Fracture
Treatment of osteoporotic kyphosis
Vertebral augmentation
Scheurmann’s disease + presentation
Thoracic kyphosis present in adolescants
Pain in the back and difficulty breathing
Cause of lumbar lordosis x2
Weakness of the trunk muscles
Psoas dysfunction
Dermatomes of sciatic nerve
L5 and S1
Other than at the back - common presentation of flat back syndrome
Slight bend in the knees (due to internal rotation of the thigh)
Schmall’s does and condition in which these are present?
Depression in the vertebra at the nucleus propulsus due to Scheurmann’s disease
Most common region for scoliosis
Thoraco-lumbar region - thoracic abnormal curve and this then compensated for by lumbar curve
Different stages of scoliosis and when you treat these
<20 degrees - do nothing
20 - 40 degrees - wear a brace
>40 degrees - surgical options
‘Syndesmophyte’
Osteophyte present at the verterbral column
NB. Osteophyte technically only present at synovial joints
‘Cauda equina syndrome’
Posterior dislocation of vertebral body - compression of the cauda equina - multiple nerve endings
‘Discectomy/
Removal of the IV disc
‘Laminectomy’
Removal of lamina of the spinous process
‘DISH’
Diffuse idiopathic skeletal hyperostosis
Ossification of the anterior longitudinal ligament
