MSK Flashcards
What are some examples of perinatal disorders?
Congenital scoliosis - abnormal curvature of the spine, usually in the coronal plane.
The most common type of scoliosis is idiopathic but a known cause of scoliosis is congenital malformation of the spine. This can occur when the vertebrae fail to separate or form properly during foetal growth (around the 4th to 6th week gestation), and is often part of a more widespread foetal develpment disorder, that includes the heart, gastrointestinal and genitourinary systems.
Congenital deficiencies - a collection of disorders that result from the failure of formation of a bony part of the body, like fibular hemimelia, which is a congenital absence of the fibula, leading to a shortened, bowed tibia on the affected side.
Hand deformities - radial club hand (radius failed to form, incomplete formation of thumb), syndactyly (fingers failed to separate properly), polydactyly (duplicated finger), central deficiency (no middle/ring finger).
DDH - developmental dysplasia of the hip - acetabulae fail to form properly and as a result of this, the femoral heads fail to form properly as the child ages.
What are some examples of growth disorders?
Achondroplasia - a skeletal dysplasia caused by a pathology in the physes of long bones causing disproportionate dwarfism (trunk/limb imbalance).
Endocrine causes - too much or too little of a hormone, like the thyroid hormones or human growth hormone, really tall due to an overproduction of human growth hormone from a pituitary tumour resulting in acromegaly. Really short due to primordial dwarfism, which in itself is a term used to refer to 1 of 5 genetic, rather than endocrine, disorders.
Nutritional causes - rickets due to lack of Vitamin D.
Physeal arrest - trauma.
What are some examples of soft tissue degeneration?
Slipped/herniated disc - due to repeated microtraumas to the intervertebral discs over a patient’s lifetime, happens when the nucleus pulposus (inner part of the disk) bursts through the worn annulus fibrosis (outer part) causing severe back pain and occasionally pressing on a nerve or the spinal cord itself.
Meniscus tear from degeneration - makes more likely to tear.
Shoulder impingement - rotator cuff tears, ACJ arthritis from wear and tear, making the tissues fibrilated and more likely to tear.
What are the metabolic skeletal functions?
Blood cell production, metabolic storage and homeostasis.
What is the function of red bone marrow?
Where does it exist?
Red bone marrow is where the production of blood cells takes place, a process known as hematopoiesis, hemato- =“blood”, -poiesis = “to make”.
Red blood cells, white blood cells, and platelets are allproduced in red bone marrow.
It exists mainly in non-long bones of the body.
How to bones serve as a site for blood cell production?
Via the unique connective tissue that fills the interior of most bones, the bone marrow.
There are two types of bone marrow: yellow bone marrow and red bone marrow. Red is where blood cell production occurs.
What is the function of yellow bone marrow?
Where does it exist?
Yellow bone marrow contains adipose tissue, and the triglycerides stored in the adipocytes of this tissue can be released to serve as a source of energy for other tissues of the body.
Mainly in the medullary cavity of long bones’ shaft.
What is the metabolic function of bone?
Storage:
Fat in yellow bone marrow,
A number of minerals important to the functioning of the body, especially calcium, and phosphorus in the actual bone.
These minerals, incorporated into bone tissue, can be released back into the bloodstream to maintain levels needed to support physiological processes.
Calcium ions, for example, are essential for muscle contractions and are involved in the transmission of nerve impulses.
What are the main drives of bone metabolism?
Bone metabolism is driven by the cycle of deposition by osteoblasts and resorption byosteoclasts, sequestering and releasing calcium and phosphate to and from thecirculation.
What is the mechanical function of bone?
Structure,
Motion (anchor point for soft tissue - muscles of movement and organs),
Protection (skull protects head organs, spine the spinal cord, ribs the lungs/mediastinum, pelvis; notice these are all flat bones),
Hearing (specialised bones - auditory ossicles - malleus, incus, stapes),
Breathing (diaphram attached to bones - xiphoid process, costal margin, ribs, thoracolumbar spine - creates vaccum for air into lungs, creates pressure to vomit, urine, feces, prevent acid reflux; intercostal muscles also help forced ins/ex-piration during activity)
What are some adaptations for bipedalism?
Spinal curves - lumbar/cervical lordosis and a thoracic kyphosis which prevents vertibral column from leaning forward, keeping everything directly above the centre of balance; means less energy to stand upright. These also act like compressive springs - allow hight changes and mobility of upper body.
Intervertebral discs - shock absorbers which, combined with the compressive spring arrangement of spinal curvatures, dampens the heavy impacts that come with the whole body weight landing on single limb during walking, running or jumping.
Weight bearing axis of hip and knees - enalarged hip and knee joints to cope with increased forces, shorter and broader shaped pelvis to decrease lever length so muscles of hip abduction don’t need towork as hard to stand on one leg. Longer legs improves the lever effect for muscles and also improves the pendulum swing of the leg, preserving moreenergy during walking. Human femur angle medially, keeping the knees and ankles directly underneath body at all points during walking, increases power and allows locking kneea to use minimal power to stand for extended periods. Gluteus maximus prevents body pitching forwards and extends hip, propelling forward when running.
Tripod arrangement of foot - enlarges ankle bones, especially calcaneus and calcaneus, great toe and small toe MTP joints make arch which absorbs energy when stretched and propels forwards when released, reducing overall energy expenditure while moving.
Soleus - ‘slow’ muscle maintains standing posture, stopping dorsifelxion.
What are osteogenic(osteoprogenitor) cells?
Mesenchymal stem cells (derived from foetal mesencyme) that differentiate into various different specialised bone cells. Precursors to adipocytes, myocytes, chondrocytes and osteoblasts.
Depends on the mechanical environment they exist in and chemical signalling:
Minimal movement (strain) - become osteoblasts, signalled by RunX2 and osterix, released by osteocytes that sense movement via mechanotransduction
More movement - become chondrocytes
They can be present within the bone marrow, the endosteum and the cellular layer of the periosteum.
What are octeoblasts function?
Two functions:
1. Formbonebyproducingnon‐mineralisedmatrix - have more endoplasmic reticulum, golgi apparatus, mitochondria, allowing synthesis and secretion of bone matrix.
When stimulatedbyPTH,theyproducetype1collagenandalkalinephosphatase (enzymethatdephosphorylatesmanyorganicmolecules)initiatingthecalcificationofthematrixbylayingdowndepositsofcalciumphosphate.
TheyalsohaveavitDreceptorandwhenstimulated,OBsproducematrix,alkalinephosphataseandspecificboneproteinslikeosteocalcinandosteonectin.
- RegulatingosteoclastfunctionviatheRANK/OPGaxis - inresponsetoPTH,osteoblastsreleaseRANK‐Ligandwhichisasignallingmoleculethatbindstothecorrespondingreceptor,RANK,stimulatingosteoclastprecursorstobecomeactiveosteoclasts,thusstimulatingboneresorption.
Theyalsosecreteosteoprotegrin,whichisadecoyreceptorthatirreversiblybindstofreeRANKligand,preventingitfromattachingtoRANKontheosteoclastprecursors.Osteoprotegrinthereforeinhibitsthedifferentiation,fusionand activationofosteoclastsandthereforepreventsboneresorption.
What are osteoclasts?
Multinucleatedgiantcells,formed fromthefusionofmultiple myeloidhaematopoieticcellsfromthemonocyte/macrophagelineage.
They reabsorb bone by firstdissolvingtheinorganichydroxyapatiteandthentheorganicmatrixbyproteolyticdigestion.
Theyhavereceptorsontheirsurfaceforcalcitonin,whichinhibitstheiractivityandareactivatedbyRANK‐Ligand.
RANK-L causes osteoclast progenitor cells to fuse together and migrate to site of bone resorption, attach to bone surface and become active.
Forms a ruffled border at bone surfacethenreleasesvarioussubstancesincludingtartrateresistantacidphosphate,knowasTRAP,whichhelpsdissolvetheinorganichydroxyappetite,andproteolyticenzymes likecathepsinK,whichbreakdowntheorganiccomponents.
Resorptionofboneformsasmallpit,knownasHowship’s lacunae.
Theruffledborderthenresorbstheorganicandinorganicproductsofdegradationfromthe Howship’s lacunae,transportingthemacrossthecellforexcretionviathesecretorydomain.
What are osteocytes?
Former osteoblasts trapped in matrix, account for 90% cells in mature skeleton. They maintaintheboneandcellularmatrix,regulatingtheconcentrationsofcalciumandphosphorusinbone.
Long cellular processes for communication through smallchannelsinthebonecalledcanaliculi (part of haversian system).
Sense via mechanotransduction movement of fluid that happens when tissue is placed under compressive load, then can signal over long distances via their cellular processes.
Regulate bone remodelling in response to local mechanical or systemic (PTH) signals.
How are octeoblasts formed?
What is osteoblasts fate?
Mono-nucleated, form from osteoprogenitor cells, that differentiate intoPre‐OBtoOB under theinfluenceofsignallingfactors RunX2andosterix.
Lifespan of about 6 months, then;
1. 10-15% becomeentombedinthematrixtheyhaveproducedandbecomeosteocytes.
2. Die by apoptosis
3. Differentiateintoliningcells,thatsitonthesurfaceofquiescentbone - these areflattened,inactiveosteoblaststhathavethepotentialtobecomematureosteoblastsforfutureremodelling.
How do osteocytes respond to signals?
They regulate bone remodelling in response to local mechanical or systemic (PTH) signals.
Increase osteoclast formation by increasing RANK-L, leading to bone resorption.
Inhibits osteoblast formation by producing sclerostin, decreasing bone formation.
PTH and mechanical loading inhibits sclerostin production, increasing bone formation.
Inducesrapidcalcium release (osteocytic osteolysis) in response to PTH levels increasing.
What are the zones in active osteoclasts?
What is the area of the bone underneath it called?
Sealing zone - one side of cell seals to bone surface
Secretory domain - cell surface away from bone where products of degradationarereleasedintotheinterstitialfluid
Ruffled border - at bone surface, this increases the surface area, aiding secretionandabsorptionofenzymesandproductsofdegradation
Resorptionofboneformsasmallpit,knownasHowship’s lacunae.
What is bone?
Arigidorganwithavarietyoffunctionsincludingstructural,endocrineandmetabolic.
What is bone tissue?
Dense connective tissue with;
High compressive strength (pushed together), low tensile and shear strength (pull apart), rigid but significant elasticity
It is ananisotropicmaterial as strengthisdependantonhowaloadisapplied.
How do you classify bone anatomically?
Flat - thin,flatorcurvedbonesthatsandwichathinlayerofcancellousbonebetween2layersofcortex (majority of skull, sternum)
Short - roughly cube-shaped (carpals, tarsals)
Sesamoid - exist in tendons, improvethepowertheattachedmusclebyholdingthetendonfurtherfromthecenter ofthejoint,therebyincreasingitsleverage (patella, pairofsesamoidsunderthegreattoemeta‐tarsophalangeal joint)
Irregular - unique shape for individual purpose (vertebrae)
Long - havethreeanatomicregions; epiphysis,metaphysis andthediaphysis (femur, phalanges)
Describe the structure of long bones.
Threeanatomicregions;
Epiphysis - end forming articular surface, covered by articular cartilage with physis and subchondral region underneath
Metaphysis - thin cortical bone surrounding loose trabecular
Diaphysis - thick cortiical bone surrounding central canal of bone marrow, outer region covered by the periosteum which is whichisdense,irregularconnectivetissuethat provides blood supply to the bone and provides fibroblasts and progenitor cells that can develop into osteoblasts/chondroblasts. Inside the medullary cavity there’s an endosteum which helps bone turnover and remodelling.
What is the physis?
The growth plate - aspecialised zoneofcartilagelocatedattheendsoflongbonesthatisresponsibleforlongitudinalgrowth. Fuses as a child becomes an adult
How do you classify bone by it’s macroscopic structure?
Cancellous (trabecular/spongy) - most in epiphysis and then metaphysis, less bending force so don’t need thick cortices to withstand them; mainly experience commpressive forces (especially sudden shock as weight is applied to joint) so supports articular surface, resists impact and transfers weight evenly
Cortical (hard) - diaphysis of long bones is mainly cortical, strong and rigid, good for big lever for multiplying great force over long distances, resists bending forces of muscles; slow turn-over rate
In diaphysis and mid-bone (metaphysis) mainly cortical woth a little cancellous.
At isthmus, in long bones diaphysis, thickest cortices and narrowest medullary canal.
How is cortical bone organised?
Main structural unit is an osteon - 2-3mm long cylinder with 8-15 concentric rings of bone called lamellae, each 0.2mm wide.
Their axis is parallel to the long axis of the bone.
Has channels containing neurovascular sytuctures called Haversian canals, if parallel to axis of bone; called Volksman’s canals if perpendicular to long axis of bone. Together these form neurovascular network throughout the bone, connecting individual osteons.
How is cancellous bone organised?
A loose network of struts - makes it less rigid, more elasic than cortical.
Has a high surface area for metabolic functions so important for Ca homeostasis since high turnover compared to cortical, and can remodel quickly according to stress.
Trabeculae are organised along lines of maximum mechanical stress which act like struts and arcs of a bridge - gives a lot of strength wihtout weight of solid bone, allowing for effective transmission of loads, supporting areas of maximum stress.
How is bone organised microscopically?
Two types:
Woven bone - immature bone formed rapidly (foetal growth, fracture); collagen fibres organised haphazardly, not stress orientated so mechanically weak
Lamellar bone - highly organised, stress orientated, made by remodelling woven bone; collagen fibres in parallel sheets/lamellae so structurally strong as organised, stress orientated pattern
Describe the composistion of bone.
40% organic bone matrix (osteoid)
60% inorganic (calcium hydroxyapatite)
Describe the organic part of the bone matrix (the osteoid).
Makes up 40% of the bone.
90% of it is type one collagen, providing bone with tensile strength.
Rest is non-collagenous proteins;
proteoglycans (contribute to compressive strength) and matrix proteins (osteocalcin, osteonectin, osteopontin).
Most abundant non-collagenous protein is osteocalcin, produced by mature osteoblasts, promotoes mineralisation and formation of bone and attracts osteoclasts - clinical marker of bone turnover (serum/urine).
Cytokines and growth factors in matrix too - aids cell differntiation, activation, growth, turnover. Includes interleukins 1 and 6, insulin‐likegrowthfactorandbonemorphogeneticproteins.
Describe the inorganic part of the bone matrix.
Makes up 60% bone.
Calcium hydroxyapatite - suuports and gives bone compressive strength (so do proteoglycans in organic); main form Ca is stored in the body.
What are the functions of Calcium?
Structural - hard component of bone, without Ca salt hydroxyapatite, bones less dense and strong
Muscle - Ca ions vital for contraction cycle; action potential reaches motor endplate and triggersthedepolarisationofthemusclessarcoplasmicreticulumandbeginsexcitation‐contractioncoupling
Ion channels - nerve action potential depends on voltage-gated ion channels sensitive to [Ca2+] in plasma, decreases in serum Ca cause ion channels to leak Na, making them hyperexcitable, increase means more Ca binds to these channels preventing depolarisation. So [Ca2+] levels off interfere with muscle and nerve function, causing cardia arryuthmias, muscle tetany, weakness.
Protein binding - like in the clotting cascade
Cell signalling - neurotransmitter release
What is the Calcium concentration in serum?
Total plasma concentration: 2.2 - 2.6 mmol/L
35-50% bound to protein, 5-10% in complexes with organic acids/phosphates. The remaining 50-60% is ionised and what is measured. It’s clinically relevant in identifying ionised/total Ca imbalance like when serum proteins like albumin levels are low.
What is the differnce between serum and intracellular concentrations?
Why is this important?
Intracellular concentration 7000x lower than blood plasma.
Means cell sugnalling is very powerful as tiny amounts of Ca entering cell can be detected.
How does the body respond to hypercalcaemia?
- Ca concentration risen above normal detected by thyroid
- Thyroid releases calcitonin
- Calcitonin acts on kidneys to reduce renal uptake of Ca so more lost in urine.
- Calcitonin also inhibits osteoclasts so less Ca released into circulation from bone.
- Serum Ca levels drop back to normal levels.
How does the body respond to hypocalcaemia?
- Parathyroid gland detects serum Ca concentration drops below normal
- It releases parathyroid hormone (PTH)
- PTH stimulates osteoblasts, which have PTH receptor on surface, increases interleukins and macrophage colony stimulating factor and RANKL, these all stimulate osteoclast activity, reabsorbing bone
- PTH also stimulates vitamin D hydroxylation to calcitriol in kidneys, PTH and calcitriol together increase RANKL from osteoblasts, and increases Ca uptake in kidneys and intestine.
- Osteoclast activation slow, intestinal uptake intermediate, renal uptake fast, all increase Ca levels to normal homeostasis.
How do the intestines influence intake and excretion of calcium to affect concentration?
Normally 20mmol Ca absorbed by intestines per day by binding to calbindin as it brushes intestinal epithelial cells, which is a vitamin D dependent protein, absorption of Ca is reglated by calcitriol (active vit D).
Intestines get 15mmol Ca from excreted bile which combines with the 25mmol we get from diet, so about 40mmol passes through.
Intestines also excrete Ca via bile so net gain is about 5mmol.
How do the kidneys influence intake and excretion of calcium to affect concentration?
They filter about 250mmol Ca per day and reabsorb about 245mmol, so net loss of 5mmol.
Calcitonin - increases renal excretion (inhibits reabsorbtion).
PTH - major affer is stimulating process of vitamin D to calcitriol, minor affect reducing renal excretion.
How do bones influence calcium concentration?
10mmol exchanged everyday.
Calcitonin from thyroid directly inhibits osteoclasts.
Osteoblasts indirectly stimulate osteoclasts by releasinf RANK-L under influence of PTH.
What controls serum calcium concentration?
Chief cells within the four parathyroid glands (located on the back of neck thyroid gland) release PTH (parathyroid hormone) which is most importnat regulatory hormone of [Ca].
Fall in [Ca] detected by PTH receptors which then synthesise and release PTH into blood. This acts on kidneys, intestines, osteoblasts and, indirectly, osteoclasts.
Also releases calcitonin from parafollicular cells, opposing PTH action, directly inhibiting osteoclasts.
Oestrogen also inhibits RANKL release from osteoblasts, reducing osteoclast activity and bone resoption (lost in menopause - lower bone density).
How is vitamin D acticated?
What does it do?
Must undergo two hydroxylations, first in liver, making 25hydroxyvitaminD; then in kidney, making calcitriol (1‐25dihydroxyvitaminD).
Conversion in kidneys is stimulated by PTH or low serum calcium.
Calcitriol has 3 main actions:
Stimulate osteoblasts to release RANK-L to stimulate osteoclasts and increase absorption and reabsorption in GI tract and kidneys.
What is bone remodelling?
The cycle by which small increments of bone are removed and then replaced by new bone.
Why is bone remodelling necesary?
Micro-trauma from everyday life results in micro-damage/micro-fractures which would weaken the bone leading to further damage of bone around them, eventually resulting in mechanical failure (fractures) if not repaired.
It is needed to repair macro-damages (fractures).
Allows bones to change in response to changing loads.
It is needed for calcium homeostasis.
How frequently are bones remodelled?
5-15% of the surface of adult bones are normally undergoing remodelling.
In a year, about 18% of an adult skeleton is replaced - 20% of cancellous bone and 2% of cortical bone is replaced.
What are the six stages in the bone remodelling cycle?
Six stages:
1. Quiescence - dormancy
2. Activation - RANKL, PTH, M-CSF, vit D
3. Resorption - osteoclasts migrate to bone and break it down
4. Reversal - osteoblasts activated by osteoclasts
5. Formation - osteoblasts lay down osteoid
6. Mineralisation - hydroxyapatite deposited
What happens during the quiescence stage of the bone remodelling cycle?
90% bone in state of inactivity/dormance.
Osteoblasts are flattened inactive cells lining bone surface, osteocytes maintain and monitor bone for local changes and produce sclerostin - protein that inhibits osteoblastic activity to keep in resting state.
What happens during the activation stage of the bone remodelling cycle?
Local/systemic signallers bring it out of quincience stage.
Local - osteocytes detect stress/micro-damage and signal to osteoblasts to release RANK-ligand and macrophage colony stimulating factor (M-CSF).
Systemic - PTH and vit D, as well as some endocrine hormones like thyroid and growth hormones (oestrogen and calcitonin are antagonistic to this, inhibiting bone resoption)
These begin the recruitment, differentiation and activation of osteoclasts.
What happens during the resorption stage of the bone remodelling cycle?
RANKL/M-CSF activated osteoclasts begin resorption process:
- attach to bone with tight seal around edge
- polarose themselves, forming ruffled border near the bone, and functional secretory domain on far side
- release hydrochloric acid from ruffled border, dissolving inorganic bone (hydroxyapatite), forming resorption pit
- release protease to dissolve organic matrix
- transport degredation products to be secreted through the functional secretory domain
What happens during the reversal stage of the bone remodelling cycle?
Osteoblasts migrate to resorption pit because of signals while osteoclasts are regressing to their inactivate state.
They differentiate and activate due to direct osteoclast to osteoblast signalling molecules.
What happens during the formation stage of the bone remodelling cycle?
Activated osteoblasts lay down organic bone matrix - osteoid.
Osteoid is made of type one collagen with various bone proteins like osteocalcin and proteoglycans. It fills the resorption pit.
The osteoblasts then control the mineralisation of the osteoid.
What happens during the mineralisation stage of the bone remodelling cycle?
This happens concurrently to formation stage producing osteoid. 75% happens in first week or two, then the rest in weeks-months.
Hydroxyapatite crystals are deposisted, forming the inorganic matrix (made of calcium and inorganic phosphate).
This turns the unmineralised osteoid from soft to hard mineralised bone.
What regulates bone mineralisation?
Local - presence of inorganic pyrophosphate (PPi) act as a inhibitor to mineralisation, so in fluid like synovial fluid where Ca and PO4 present but mineralisation would be bad, acts as a feedback loop;
Osteoblast-derived proteins (osteocalcin promotes but osteopontin inhibits mineral binding).
Systemic - PTH, vit D, fibroblast growth factor 23 (FGF23 - increases PPi, decreases PTH/vitD).
What are the two mechanisms of bone formation?
Intramembranous ossification - osteoblasts lay down osteoid within loose fibroconnective tissue of a fibrous membrane, no prior structure.
Endochondral ossification - osteoid is deposited on an existing cartilage scaffold, most bones in developing feotus produced this way.
When does intramembranous ossification occur?
In foetus, flat bones of face, most cranial bones, clavicles formed this way.
In primary healing of fractures (when treated with solid metal plate forcing the ends together with no movement).
When bones grow in width (appositional growth), intramembranous ossification occurs at the periosteum or perichondrium at the physis. This relys on matching resorption of bone on inner surface of diaphysis by cells on endosteum.
What is intramembranous ossification?
How is it formed?
Bone develops directly from sheets of undifferentiated mesencymal cells without a cartilage model.
Mesenchymal cells in embryonic skeleton proliferate in fibrous tissue, some differnetiating into osteogenic cells which become osteoblasts.
Osteoblasts cluster to form the ossification centre, which produces osteoid (random arrangement of woven bone), in which hydroxyapatite is deposisted within a few days.
Osteoblasts become trapped and transition into osteocytes, mesenchymal cells surrounding ossification centre replenish osteoblast supply.
As the bone matures, trabecular network of calcified matrix develops around the blood vessels, periosteum forms from surface osteoblasts and mesenchyme.
Then compact cortical bone forms below periosteum and blood vessels in the trabecular bone condense into red marrow.
How are primary centres of endochondral ossification formed?
Osteoid is deposited and mineralised ontop of preformed diaphyseal cartilage scafold while the cartilage is being removed.
In early foetal development mesenchymal cells differntiate into chondrocytes, forming cartilaginous skeletal precursor. The perichondrium forms on the surface.
Perichondrium becomes the periosteum, producing thin layer of bone on surface of the diaphyseal cartilage (periosteal collar).
As more cartilage matrix is produced, chondrocytes at the centre of the scaffold enlarge and begin to calcify the matrix which prevents nutrients from reaching the chondrocytes, so they die and surrounding cartilage disintegrates.
Blood vessels invade spaces left by disintegrated cartilage, carrying osteogenic cells, so primary ossification centre forms in middle of cartilage scaffold (ossification begins).
More cartilage forms at ends of bones, increasing length, diaphyseal cartilage being replaced with bone.
When does endochondral ossification form?
Osteoid is deposited on preformed cartilage.
Most of skeleton developed this way, how the physis facilitate longitutinal growth and involved in ‘secondary healing’ of fractures, when not fully immobilised (forms soft callus cartilage then replaced by hard woven bone and remodelled into lamellar bone).
What is endochondral ossification?
Osteoid is deposited and mineralised ontop of preformed cartilage scafold while the cartilage is being removed.
How are secondary centres of endochondral ossification formed?
Osteoid is deposited and mineralised ontop of preformed cartilage scafold of epiphysis while the cartilage is being removed.
Chondrocytes die in the calcified matrix, blood vessels infiltrate along with osteogenic cells and ossification occurs.
Secondary ossification centres form at birth in predictable way - can age child from skeleton.
What are traction epiphyses?
Secondary ossification centres formed in non-weight bearing part of bone (like greater trochanter of femur), at ligament/tendon attachment sites.
What contributes to cessation of growth?
Epiphyseal growth plates close, when depends on sex and physis location. But generally 14 in females, 16 in males.
It is genetically determined - average both partents, subtract 6cm for female, add 6cm for males.
Ostrogens/Androgens initially increase growth hormone secretion in early puberty and increase bone growth but later induce closure of growth plates.
Premature growth plate closure leads to shortened bones.
Caused by systemic disease (leukemia), poor nutrition, endocrine deficiencies (growth hormone), thyroid problems, infection, osteomyelitis, trauma…
What are the physis?
What are they responsible for?
Hyaline cartilage plates at ends of long bones.
Bone longitudinal growth at actual physis (endochondral ossification), circumferential growth at the perichondrium (ntramembranous).
Describe the macroscopic structure of the physis.
Secondary ossification centre - forms new bone.
Physis - zone of provisional calcification (ZPC) and primary groeth plate.
Perichondrium - encircles outer edge of physis, perichondral ring (at ossification groove) is continuous with the metaphyseal periosteum, increasing strength of attachement of bone and physis.
How is blood supplied to the physis?
Why is blood supply important?
Three main routes:
- Perichondral artery - main blood supply to the physis
- Epiphyseal artery - supplies resting zone
- Metaphyseal arteries - supplies metaphyseal spongiosa
Bone growth highly vascular as needs constant energy and building blocks. Any interuption is very bad (like in Perthe’s disease of the hip).
What are the microscopic zones of the physis?
How do chondrocytes differ at each zone?
Resting zone (at the epiphyseal end)
Proliferation zone
Hypertrophic zone (zones of maturation, degeneration, provisional calcification)
Metaphyseal bone (primary/secondary spngiosa)
Chondrocytes sparsely packed at ephiseal end in resting zone, as move towards metaphysis, cells multiply and line up in columns longitudinally and increase in size.
As the cells go through changes they remain stationary and the actual physis itself migrates.
What happens at the resting zone of the physis?
At the epiphyseal end, contains sparsely packed chondrocytes, not curently changing size/producing matrix.
They contain large lipid stores, glycogen, and proteoglycans for future growth/matrix production.
Epiphyseal arteries supply blood.
What happens at the proliferation zone of the physis?
Stimulated choondrocytes stack up in columns and multiply at increased rate.
They begin to produce cartilaginous ECM (similar structure to bone without Ca to make rigid) and will continue to do this throughout transition (but highest rate here).
What conditions occur from defects at the proliferative zone of the physis?
Defects alter rate cells multiply, causing decreased/increased bone length as in achondroplasia and gigantism.
What happens at the hypertrophic zone of the physis?
After cells multiplied many times in proliferation zone, proceed to increase size many times in three hypertrophic sub-zones (maturation, degenration, provisional calcification).
As they increase size, chondrocytes collect and store Ca to release when they die.
What can go wrong in the hypertrophic zone in the physis?
It is a relatively weak point in physis so site of slipped upper femoral epiphysis (SUFE) and Salter-Harris fractures.
What happens at the zone of maturation in the physis?
First of hypertrophic zones, cells differentiate, mature, and slowly increasing size until double.
What happens at the zone of degredation in the physis?
Second of hypertrophic zones, chondrocyes have a 5-fold increase in size, becoming almost too big too survive so must undergo apoptosis (in third zone -of calcification).
What happens at the zone of provisional calcification in the physis?
Third (and last) of the hypertrophic zones, now massive chondrocytes die by apoptosis and release Ca they have stored up to calcify surrounding matrix.
What happens at the metaphyseal bone during growth at the physis?
Next to the dying chondrocytes, osteoprogenitor cells and blood vessels infiltrate the calcified matrix, rapidly lay down immature, woven bone (primary spongiosa).
This immature bone is then remodelled in the secondary spongiosa to make the highly organised structure of lamellar bone (takes much longer than rapid production of woven bone, months).
What is Achondroplasia?
A disease of the physis, most common skeletal dysplasia.
From defect in Fibroblast Growth Factor Receptor 3 (FGFR3) gene.
Causes increased inhibition of chondrocyte proliferation in proliferation zone. Autosomal dominant inheritance but 80% new mutations.
‘Disproportionate dwarfism’ as affects different body parts differently and doesn’t affect trunk. Follows ‘rhizomelic’ pattern as proximal limbs affected more than distal.
What is Gigantism?
Disease of the physis causing hight well above average (>2.1m).
Excess growth hormone leads to increased proliferation of cells in proliferation zone.
Normally caused by a pituitary adenoma.
Causes gigantism in children but in adults, because physis are closed, causes acromegaly (hands, feet, forehead, jaw, nose increase in size).
What is the normal immature gait?
When does the gait mature?
Early walking: short Stride length, fast cadence, low Velocity, widened base of support (until 30-36 months), can’t stand on one leg.
Mature gait develops around age 7.
What causes an abnormal gait in children?
Often atraumatic, incidence of 180/100,000 so common.
Limp caused by pain (legs, pelvis, lower back), mechanical problem (dysplasia), neuromuscular problems.
What is the common MSK conditions causing limping in children ages:
0-2
2-8
4-8
13-16
0-16?
0-2: DDH
2-8: Transient Synovitis
4-8: Perthes’
13-16: SUFE
0-16: Tumour/septic arthritis/neuromuscular
What does acute, contant, morning/after inactivity, night pain suggest in a limping child?
Acute - trauma, infection
Constant - malignancy, chronic infection
Morning pain/pain after inactivity - Inflammatory joint disorders
Night Pain - malignancy, osteoid osteoma, benign “growing pains”
What do you have to check during exaination of a limping child?
Gait
Spine
Asymmetry
Deformity
Swelling
Tenderness
Examine all joints
Rotational profile
What is Transient Synovitis?
What are the clinical investigations and treatments?
Irritable hip, very common in ages 2-5.
Non-specific, short term inflammatory synovitis with synovial effusion of the hip joint.
Clinical features:
Painful hip/thigh/knee
Often associated with viral infection
Synovial fluid effusion
Hip held in flexion, lateral rotation and abduction
Exclusion of other conditions (mainly infection/sepsis)
Investigations:
Full blood count
ESR, CRP
X rays (AP & frog lateral)
Ultrasound (look for effusion, should be small or none)
MRI, bone scan… (not routine)
Paracetamol and ibuprofen, but self limiting.
What is developmental dysplasia of the hip?
What are the risk factors?
DDH is when accetabelum is less rounded so hip is more prone to dilsocation.
Risk factors are genetic, breach after 32 weeks or Caesarian, 1st Born, Oligohydramnios in womb, females 5x more likely.
Identification of risk factor will lead to formal examination.
What are the examinations for checking for DDH?
Barlows - test if hip is dislocated, (B for brutal), legs to 90 degrees flexion and then push knees, trying to dislocate, should feel clunk as easily dislocate in DDH
Ortolani - test if hip is dislocated, (O for out), hip already dislocted, bring hip out to abduction and feel clunk back in
Other things to look for:
Deepening skin crease/asymetry
Leg length discrepancy (especially in older infants after 6-8 weeks) by the Gally-atsy test
Reduced abduction (especially in older infants after 6-8 weeks), should be able to get to frog position
Also x-ray, checks if hip is in socket…
Ultra-sound confirms
Try pick up <6weeks.
What is treatment for DDH?
Infants - Harness to hold hips adducted and flexed, regular checks.
If treated early, 95% success.
Older infants (3 months) - surgery
What is Perthes’ Disease?
What are the risk factors?
Osteonecrosis (avascular necrosis) of femoral epiphysis caused by poorly understood non-genetic factors, flattened, fragmented femoral head on x-ray but socket normal.
Normally ages 4-8, 4x as likely in boys, more common in lower social class, likely due to smoking.
What is the treatment of Perthes’ disease?
Principles are prevention of stiffness, contain femoral head in acetabulum (containment, sometimes need surgery), keep moving - needs a good physio for 2-3 years. Normally blood supply will return on its own.
Surgical treatment required in certain circumstances (tip head down into socket), outcome depends on how well femoral head remodels.
What is Slipped Upper Femoral Epiphysis?
What are the risk factors?
SUFE is metaphysis slipping off of epiphysis.
Normally in ages 13-16, males 3x more likely, younger in females (not after menarche), obese/tall and slender, rapid growth, genetic - 7% risk 2nd family member involved.
Overweight big factor so increasing incidence.
Bilateral in 42% so often treat both sides.
What are the clinical features and treatment for SUFE?
Acute/chronic/acute on chronic pain in groin, thigh, knee. Often boy, slightly overweight with knee pain due to referred pain.
Limp, antalgic gait, externally rotated and adducted limb.
Frog lateral x-ray good to see.
Treatment is surgery to pin in situe to remodel in good position, epiphysis to diaphysis. High rate of bilateral and stops leg length discrepancy so do both sides.
What are red flags for paediatric MSK?
Neonate with painful paralysedlooking arm or leg, even without fever/other signs (septic arthritis/infection)
Asymmetry of spine or limbs (scoliosis (forward bend test)/DDH)
School age child with limp (Perthes’ disease)
Knee pain in adolescent (SUFE/tumour)
Back pain (discitis)
NAI (especially <1year)
What infections can cause limping child?
What emergency protocol needs done?
Cellulitis (skin infection)
Osteomyelitis (bone infection)
Septic arthritis (joint infection)
Usually requires emergent referral for investigation +/- aspiration.
What is discitis?
Inflammation of the vertebral discs.
Presentation can be subtle so usually MRI required.
Normally inflammatory but hard to get sample so treat with antibiotics.
Epidural abscess (if bacterial) is surgical emergency.
What could painless atraumatic swelling be?
Tumours:
Ewings tumours in infants
Osteosarcomas in adolescents (especially around knee)
Get x-ray, early diagnosis is key.
What should raise suspicion for NAIs?
Pre-existing disability, vague history, inconsistent history with injury, delay in presentation, multiple bruises of varying age, multiple fractures, burns.
How are children’s bones different from adult bones?
More numerous as some fuse in adulthood like ilium/ischium/pubis in pelvis, open physis (dark lines on radiograph), ossification centres (lighter circular areas). These are predictable.
The bones are less rigid and brittle, much more elasticity (bend and spring back) and plasticity (bone changes permanently).
Periosteum covering diaphysis surface is much thicker (like leather) which makes fractures easier to reduce as periosteum remains intact so bones don’t displace as much.
What fracture patterns in bones are typically seen in children?
Greenstick fracture - on tension side (where force is applied) as bone pulled apart but crack only part way across bone.
Buckle/torus fracture - on compression side (opposite tension side), force too great so buckles under pressure and bulges out the side.
