Bone Biology & Calcium Regulation Flashcards
What is the bathub curve? What does it tell us about conditions in the MSK system?
Shows us the different types of error/failure that occur in the MSK system across a lifetime
1. Paediatric age - developmental - disorders of formation and growth
2. Trauma - constant random failures, which are primarily related to trauma, but also to things like infection, cancer and other acute diseases - risk remains constant across all age groups
3. Wearout failures - occur at an older age - diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis.
4. Observed failure rate - accounts for all forms of failure at specific ages - i.e average - forms a bathtub
Bathtub curve allows us to divide the conditions into three age ranges - paeds (developmental), adult (trauma) and Senior (wearout) - note these are not absolutes
What are the three modes of failure observed in the paediatric population?
Paediatric population
1. Perinatal - occur during foetal development
2. Growth disorders - occur from birth to adulthood
3. Trauma, infection, cancer etc
What are some examples of perinatal MSK conditions?
-
Congenital spinal scoliosis
Abnormal curvature of the spine, usually in the coronal plane.
Most common type of scoliosis is
idiopathic - vertebrae fail to separate or form properly during foetal growth (around the 4th to 6th week gestation) -
Congenital deficiencies are a collection of disorders that result from the failure of formation of a bony part of the body.
Example - fibular hemimelia - congenital absence of the fibula
Hemimelia can occur in other long bones too, and is sometimes called a longitudinal deficiency. -
Hand deformities - Examples include…
- Radial club hand (top left)- results from child’s radius failing to form
- Syndactyly (Bottom right)
- Polydactyly (Bottom left)
- Central deficiency (top right) - DDH - developmental dysplasia of the hip - common - acetabulae fail to form properly and as a result of this, a knock on effect is the failure of the femoral heads to form properly as the child ages.
What are some examples of growth disorders that effect the MSK system of a growing child?
Growth Disorders - limited or abnormal growth of the skeleton
- Skeletal Dysplasia - e.g. achondroplasia - caused by a pathology in the physes of long bones - what we call disproportionate dwarfism - limited growth in limbs, especially proximal long bones - one example of dysplasia
- Endocrine - too much or too little hormones e.g. thyroid or human growth hormone
- Nutritional - Inadequate nutrition can also cause growth disorders - due to a lack of nutrients or childhood disease - general nutriotional deficits = reduction in height but there are also instances of specific nutrients are in short supply (e.g. Vitamin D - Rickets)
- Physeal arrest - trauma to a child’s growth plate/physis - complete or partial closure (leads to angular deformity)
What are the different types of trauma injuries that we see in the MSK?
Trauma - biggest cause of failure in the adult population
- Soft tissue - Ligament, Tendon, Menisci - commonly occurs in sports in recreational participants
- Fracture - Paediatric, adult and osteoporotic - energy applied to a bone exceeds it’s mechanical strength - adult and child fractures differ - adults bones are more rigid - higher energy required.
What are the types of ‘wear out’ injuries/conditions we see in the elderly population group?
- Increased fracture risk - osteoporosis - decreased bone density - low energy fractures - hip, wrist and spine most common - principal drivers age and hormones
- Soft tissue degeneration - Slipped discs (nucleus pulposus, the inner part of the disk, bursts through the worn annulus fibrosis), meniscal tears and shoulder impingement (rotator cuff tears and acromio-clavicular joint arthritis
- Rheumatic (inflammatory) disease - is a broad term covering a lot of MSK conditions, including RA, OA (wear flare and repair), lupus, and seronegative arthritides - ankylosing spondylitis
Note - Rheumatic disease is not just a disease of the elderly, and we do have young people and young adults who suffer from osteoarthritis and rheumatoid arthritis.
What are the general consequences associated with skeletal failure?
Failure of Skeleton
1. Pain
2. Muscle weakness
3. Loss of Function
4. Time off work/earning
5. Lack of Mobility/Independence
What are the three major functions of the skeleton?
- Haematopoietic
- Metabolic - Storage & Homeostasis
- Mechanical - Structure, protection, hearing, breathing and locomotion
Outline the skeletons role in haematopoiesis?
Haematopoiesis - blood cell production via the unique connective tissue that fills the interior of most bones, the bone marrow.
Two types of bone marrow
1. 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
2. Red bone marrow - Red blood cells, white blood cells, and platelets - mainly in non-long bones of the body
Outline the metabolic functions of bones.
Storage - reservoir for a number of minerals important to the functioning of the body, especially calcium, and phosphorus.
Calcium
Phosphorus
Fat
Acid-base
Homeostasis
Calcium/phosphate
Glucose/fat
Outline the mechanical role of the skeleton.
Structural frame
Support - structural support for the body
Motion - anchor point for soft tissues, both for the muscles of movement (lever system) and for internal organs (organisation of organs)
Soft organ protection - protective covering to soft, easily damaged structures making the axial skeleton a bit like a suit of armour - mainly formed from flat bones, which are made of a sandwich of hard cortex around a filling of cancellous bone - mechanical properties to resist impact and damage.
Hearing - has some highly specialised bones, particularly in the middle ear - chain of bones that allow for the conduction of vibrations from the eardrum to the inner ear.
Breathing - facilitate respiration - changes the volume of the abdomen facilitating expiration and inspiration.
Outline the principles behind the MSK system in locomotion?
Muscles, bones and joints act together as lever systems to produce this efficient multiplication of force.
In this lever system, the
Lever = bone,
Fulcrum / Axis = joint
Applied force = muscle attachment
Mechanically, levers are one of the fundamental simple machines that amplifies an input force to provide a greater output force.
What are the advantages of being bipedal?
- Energy conservation - It takes around 75% less energy than both quad or chimp bipedal for a human to walk upright.
- Increased endurance over long distances - hunting strategy
- Use of the upper limbs - use them for complex tasks like tool making, evolving opposable thumbs and finer motor control.
What adaptations exist for bipedalism?
- Spinal Curves - Keeps everything direcly above COB (centre of balance) meaning less muscles less energy are needed to stand upright + multiple curves of the spine act like compressive springs and allow height changes and high degree of mobility of upper body.
Less need for the heavy muscular attachments on supraorbital ridges and occipital condyles - human muscles in face, and particularly the forehead, to be used for facial expression
- Shock absorption of Discs - shock absorbers
- Wt. Bearing Axis of Hip & Knee
a) Enalarged hip and knee joints to cope with increased forces when only 2 limbs take the body’s weight
b) Longer legs than their ape relatives, which again improves the lever effect for muscles and also improves the pendulum swing
c) Human femur angle medially, keeping the knees and ankles directly underneath body at all points during walking - improves balance and allows for minimal muscle power to stand for long periods.
- Tripod Arrangement of Foot
a) Bones of the ankle are enlarged, particularly the calcaneus, for weight bearing on 2 legs
b) Highly stable tripod structure in the foot
c) Foot arch acts as a spring - conservation of energy - Soleus slow muscle
a) Achilles tendon also has this energy saving function
b) Soleus becomes key to keeping balance and maintaining a standing posture, by stopping the ankle from dorsiflexing - slow-twitch muscle - endurance
What are the 4 main types of cells found in bones?
- Osteocytes, are cells that maintain the bone tissue
- Osteoblasts, produce bone matrix
- Osteoclasts, resorb bone (meaning they remove existing bone)
- Osteogenic cells are precursor cells that differentiate into various different lines of cells depending on the mechanical environment they exist in.
Outline the role and location of osteogenic cells.
Osteogenic cells (Osteoprogenitor cells) are mesenchymal stem cells - involved in bone repair and growth
Location - within the bone marrow, the endosteum and the cellular layer of the periosteum.
OCPs fate determined by environment.
- When there is minimal movement (known as strain) in the local environment, they become osteoblasts - signalled by RunX2 and osterix which is released by osteocytes
- More movement in the local tissues, they become chondrocytes.
Clinical significance - if there is a lot of movement between fracture fragments, hard, bony callus may never form and a non-union occurs
Note - they can also differentiate into adipocytes, myocytes
Outline the role and location of osteoblasts.
Origin - Osteoprogenitor cells - in the presense of Runx2 and osterix
Location - Peri/endosteum + Bone surfaces (‘inactive’)
Functions -
1. Bone production - Form bone by producing non‐mineralised matrix
a) When stimulated by PTH, they produce type 1 collagen and alkaline phosphatase - drives dephosphorylation of oragnic molecules - initiating the calcification of matrix
b) Vit D receptor and when stimulated, OBs produce matrix, ALP and specific bone proteins like osteocalcin and osteonectin.
2. Osteoclast regulation - in regulating osteoclast function via the RANK/OPG axis
a) PTH –> osteoblasts release RANK‐Ligand –> binds to RANK receptors on osteoclasts, and stimulates osteoclast precursors to become active osteoclasts - stimulating resorption
b) Secrete osteoprotegrin (OPG), which is a decoy receptor that irreversibly binds to free RANK ligand, preventing it from attaching to RANK on the osteoclast precursors - inhibiting the differentiation, fusion and activation of osteoclasts - stops resorption
What is the fate of osteoblasts?
The average life span of an osteoblast is around 6 months, after which it can have one of 3 fates…
- About 10‐15% of osteoblast become entombed in the matrix they have produced and become osteocytes,
- Die by apoptosis
- Differentiate into lining cells, that sit on the surface of quiescent bone - potential to form mature osteoblasts for future remodelling.
What are osteocytes and what roles do they play?
Osteocytes are former osteoblasts that become trapped in the matrix - account for around 90% of the cells in the mature skeleton
Long cellular processes which are used to communicate with neighbouring cells - via small channels - canaliculi
Function
a) Osteocytes maintain the bone and cellular matrix
b) Regulating the concentrations of calcium and phosphorus in bone.
Regulation of bone remodelling is in response to this local mechanical or systemic e.g. parathyroid hormone (PTH) signals.
a) Increase osteoclast formation by increased expression of RANKL - drive resorption
b) Secrete sclerostin - inhibits osteoblast therefore decreased bone formation - sclerostin inhibited by PTH and mechanical loading
c) Responds to increasing PTH levels by inducing rapid calcium release (osteocytic osteolysis) - osteocytes involved in the dissolution of bone minerals
How do they respond to environmental stimuli? - movement of fluid and changes of pressures that occur with movement/forces - mechanotransduction (translate mechanical forces into signals)
What are osteoclasts? What is their function?
Osteoclasts are multinucleated giant cells - fusion of multiple myeloid haematopoietic cells from the monocyte/macrophage lineage.
Function - Reabsorb bone by first dissolving the inorganic hydroxyapatite and then the organic matrix by proteolytic digestion
Receptors on their surface for…
a) Calcitonin - inhibits their activity
b) Activated by RANK‐Ligand
Once activated… osteoclast progenitor cells fuse together to become multinucleate cells that migrate to the site of bone resorption and attach to the bone surface and become active osteoclasts.
Outline how osteoclasts resorped bone?
Cell polarises to have different membrane domains.
- Surface away from the bone becomes the secretory domain, where products of degradation are released into the interstitial fluid (degradation products from ruffled border secreted in the secretory domain)
- Bone surface, the cell forms a ruffled border which vastly increases the surface area of the cell to aid secretion and absorption of enzymes and products of degradation.
Releases
a) TRAP - helps dissolve the inorganic hydroxyappetite (phosphatase)
b) Proteolytic enzymes like cathepsin K, which break down the organic components.
Resorption of bone forms a small pit, known as Howship’s lacunae.
What are the different functions of calcium within the body?
Functions
1. Structural - hard structural component of bone, which is the calcium salt hydroxyapatite
2. Muscle - In skeletal and heart muscle, calcium ions are vital for the contraction cycle - release of Ca2+ from SR allowing - binding to troponin freeing actin filament binding sites
3. Ion channels - voltage gated ion channels, are sensitive to calcium ion concentration in plasma - Small decreases in serum calcium cause the ion channels to leak sodium, making them hyperexcitable (visa-versa) - abnromal Ca2+ levels interfers with neuronal function
4. Protein binding - involved in a number of physiological processes like the protein binding needed for the clotting cascade to function,
5. Cell signalling - intracellular signalling neurotransmitter release from axon terminal
What are the normal levels of Ca2+ in the plasma and inside cells?
Total plasma concentration 2.2 - 2.6 mmol/L
Note - concentration of calcium in the blood can be measured as either total plasma concentration, which is what we use clinically, or ionised calcium.
Between 35 and 50% of calcium in the blood is bound to protein and a further 5‐10% in complexes with organic acids or phospates. The remaining 50 or 60% is calcium in its ionised form
Hence… we can measure ionised calcium to identify imbalances between ionised and total calcium
Intracellular concentration 7000x lower than blood plasma - cell signalling function can be very powerful as even a tiny amount of calcium entering a cell will be detected and set off signalling pathways.
What are the different sites of Ca2+ intake and excretion?
Intake (intake from diet is 25mmol)
In the intestines, a total of about 20mmol of calcium is absorbed per day - once absorbed it is immediately bound to calbindin - vitamin D dependant protein
Note - active absorption of calcium is regulated by calcitriol, the active form of vitamin D
Excretion
Intestines excrete calcium via bile - 15mmol of calcium is excreted into the intestines in bile - some of this is reabsorbed
This means that a 40mmol passes through the intestine.
Given that 20mml is absorbed and 15 is excreted - net gain is 5mmol/day
Outline the activity of Ca2+ in the kidneys?
The kidneys filter around 250 mmols calcium a day, and reabsorb about 245mmol of this, making a net loss of around 5mmols.
In response to….
1. Calcitonin - INCREASES renal excretion (inhibits reabsorption)
2. PTH has two affects…
a) A minor effect of reducing renal excretion
b) A major effect of stimulating the processing of vitamin D into calcitriol, it’s activated form
Outline the activity of Ca in bones.
Site of Storage
- Main storages - 99% stored as calcium salts (hydroxyapatite)
- Rest of Ca2+ present in ECF and cells (1%)
Exchange approx. 10mmol/day
Turnover
1. Osteoclasts resorption releases Ca
2. PTH = Indirect stimulation - PTH stimulates RANKL release from OBs - activates osteoclasts
3. Calcitonin = Direct inhibition of Osteoclasts (from thyroid gland)
Outline the role of the Parathyroid gland in Ca2+ homeostasis.
Parathyroid gland
- Has receptors for serum calcium
- Parathyroid hormone (PTH) is released when LOW serum Ca is detected
Different effector sites…
Bone - OBs -> RANKL -> OCs
Kidneys - increase active Vit D
Intestine - increase absorption
Outline the role of the thyroid gland in Ca2+ homeostasis.
Thyroid gland
- Has receptors for serum calcium
- Releases Calcitonin (NOT CALCITRIOL) from parafollicular cells - released in response to high Ca2+
- Opposes effects of PTH
- Directly inhibits OC activity and increase secretion from kidneys
Outline the metabolism of Vitamin D and it’s role in Ca2+ homeostais.
- Vid D3, also called cholecalciferol, is obtained through 2 different routes.
a) Absorption of lipid soluble vit D in the intestines
b) UVB generation in the skin - Once absorbed or synthesed, the Vit D needs to undergo 2 hydroxylations to reach active form
a) First happens in the liver, making 25 hydroxyvitamin D
b) Second happens in the kidneys, where it is hydroxylated into calcitiol, or 1‐25 dihydroxyvitamin D.
Note - the second hydroxylation step is stimulated by PTH or low Ca2+ levels - In it’s active form (calcitriol) Vit D has three main actions…
a) Stimulating Obs to release RANKL - stimulates OCs
b) Increase absorption in the GI tract
c) Increase reabsorption in the kidneys.
Explain what happens in the body when there is hypercalaemia?
- Detection by thyroid gland
- Releases Calcitonin
- Calcitonin - acts on the kidneys to reduce renal uptake of calcium (increased excretion) & inhibit OC activity so less calcium is released into the circulation from bone.
- The net effect of this is to allow the serum calcium levels to drop
Explain what happens in the body when there is hypocalaemia?
- Parathyroid gland detects a hypocalcaemia
- Releases PTH
- PTH has multiple effects
a) PTH stimulates Obs - release RANK-L, interleukins and macrophage colony stimulating factor (MCSF) - stimulates OCs differentiation and activity - increased bone resorption - Slow response
b) PTH also stimulates hydroxylation of vitamin D into its active form (calcitriol), which happens in the kidneys
i. calcitriol - stimualtes RANK-L release from OBs
ii. calcitriol increases the uptake of calcium in both the kidneys (fast response) and intestine (medium response) - The calcium levels increase and there is a return to homeostasis
Note - Increase resorption - slowest pathway but has the highest potential to elicit change - large Ca2+ reserve.
What are the two ‘skeletons’ in the body?
- Axial skeleton
Bones of the head
Spine
Thorax - Appendicular skeleton
Shoulder girdle
Upper limb
Pelvis
Lower limb
What are the different categories of bone in the body?
Flat - thin, flat or curved bones that sandwich a thin layer of cancellous bone between 2 layers of cortex
Short - usually roughly cube‐shaped, although that can be a bit of a stretch when you actually look at them individually
Sesamoid - exist in the substance of tendons and act to improve the power the attached muscle by holding the tendon further from the center of the joint, thereby increasing its leverage
Irregular - bones don’t really fit into any category and have unique shapes that serve an individual purpose
Long - big bois
What are the characteristics of long bones?
Long bones
Three anatomic regions - epiphysis, the metaphysis and the diaphysis
- Epiphysis - end of the bone - articular surface - contains physis and subchondral region
- Metaphysis - Changing region between Epi- to Dia-physis - thin cortical bone surrounding a centre of loose trabecular bone
- Diaphysis - between the two physes at the end of the bones, and it’s made of thick cortical bone surrounding a central canal of bone marrow.
- Periosteum - dense, irregular connective tissue covering outer region of the diaphysis - roles: blood supply & provide fibroblasts and progenitor cells that develop into OB and chrondroblasts
- Involved in Fracture healing
- Circumferential bone growth
Endosteum - inside of the medullary cavity, which is primarily involved in bone turnover and remodelling
Note - any bone that has this structure of epiphysis, metaphysis, diaphysis is considered a long bone - many bones in the hand and foot are long bones –> metacarpals, the metatarsals and all of the phalanges in the fingers and toes
What are the two different macroscopic structural classifications of bone? Why do their proportions change in bone?
Macroscopic
1. Cortical
2. Cancellous
Note - Proportion of cortical / cancellous bone varies in different parts and types of the bone - related to the different mechanical requirements in the different parts of the bone.
- Mid bone / diaphysis – most cortical little cancellous bone - acts as a lever experience greater force - further from fulcrum
- End of bone / epiphysis – predominantly cancellous bone - bending forces reduce so there isn’t such a need to have thick cortices to withstand them
- Main forces experienced by the bone here are compressive forces and particulary the sudden shock forces - organised to support the articular surface, resist impact and transfer weight evenly through the bone.
Outline the structure of cortical bone.
The main structural unit of cortical bone is called an osteon
Each osteon consists of between 8‐15 concentric rings of bone, known as lamellae
Neurovascular Structures
1. Haversian canals if parallel to the axis of the bone
2. Volksman’s canals if perpendicular to the
axis
Outline the composition of bone (organic and inorganic)
Takeaways…
1. Bone has both organic and inorganic components
2. Type 1 collagen makes up most of the organic component and gives it tensile strength (not fracturing)
3. Inorganic component is calcium hydroxyapatite - calcium storage in bone and what gives it its compressive strength
Worthy mentions…
- Osteocalcin is the most non‐collagenous protein in the matrix, and it’s produced by mature osteoblasts - promotes mineralization and formation of bone and attracts osteoclasts.
- There’re also cytokines and growth factors in the matrix which aid in cell differentiation, activation, growth and turnover
Outline the general process of bone remodelling.
Remodelling is a cyclical process
4 stages
1. Quiescence
2. Resorption
3. Reversal
4. Formation
It is possibly easier to think of it as a 5 or 6 step process, which adds in activation and mineralisation as separate steps.
What happens during the quiescence stage of bone remodelling?
Quiescence - Resting state - 90% of bone
Osteoblasts are inactive and line the bone surface
Osteocytes - Maintain matrix, sense changes in mechanical environment and inhibit OB activity (sclerostin) - keeps bone in resting state
What happens during the resorption stage of bone remodelling?
Resorption
1. Activated osteoclasts migrate
2. Attach to bone
3. Polarise
4. Dissolve inorganic and organic matrix - release hydrochloric acid (inorganic) and proteases (organic) - forming resorption pit
5. Remove degradation products - transport to functional secretory domain
What happens during the reversal stage of bone remodelling?
Reversal
1. Osteoprogenitor cells migrate to resorption pit and differentiate + activate
2. Osteoclasts - apoptose or deactivate - Signal to OPCs/OBs
Activation of OBs occurs via direct contact of OBs with OCs as well as via the released signalling molecules from resort bone
What happens during the formation stage of bone remodelling?
Formation
Osteoblasts - Lay down organic osteoid, Type 1 collagen, osteocalcin, proteoglycans, etc
Note - organic matrix layed down first - followed by mineralisation
Fill in pit
Control mineralisation of osteoid - Osteopontin
Fate of OBs = osteocytes, quiescent cell lining the bone or apoptosis
What is the current thinking of the mineralisation mechanism?
Most theory seemed to centre around the generation of matrix vesicles that accumulate calcium and phosphate
These are released from the surface of osteoblasts and travel to the collagen fibrils, where the rupture and deposit their contents, depositing their contents - begin formation of crystalline hydroxyapatite.
What are the local and systemic factors influencing bone mineralisation?
Quick fire question - what are the major positive and negative regulators of bone resorption and osteoblast bone formation activity?
Outline the process of intramembranous ossification.
- Mesenchymal cells in the embryonic skeleton gather together in fibrous tissue and begin to proliferate - forming a cluster or nodule of cells
- Cells begin to differentiate into specialised cells, including blood vessels and osteogenic cells
- Osteogenic cells further differentiate into osteoblasts, which cluster together to form the ossification centre.
- Osteoblasts begin to produce osteoid (which is uncalcified matrix) in the random arrangement of woven bone.
- Osteoid then calcifies within a few days as hydroxyapatite is deposited within it - osteoblasts are trapped and converted to osteocytes
- Mesenchymal cells surrounding the ossification centre continue to differentiate so as to replenish the supply of osteoblasts
- As the bone grows more mature, a trabecular network of calcified matrix develops around the blood vessels + periosteum forms with surface OB
- Compact cortical bone forms + crowded blood vessels in the trabecular bone condense into red marrow
Outline the process of endochondral ossification.
- Early foetal development - mesenchymal cells differentiate into chondrocytes and form the cartilaginous skeletal precursor
- Perichondrium forms on the surface of the proto-bone (scaffold) - which transitions to become the periosteum
- Periosteum - produces a thin layer of bone on the surface of the diaphyseal cartilage called the periosteal collar
- As more cartilage matrix is produced, the chondrocytes at the centre of the scaffold enlarge and begin to calcify the matrix.
- Calcification prevents nutrients from
reaching the chondrocytes. - Chondrocytes die and the cartilage surrounding them disintegrates, allowing blood vessels to invade the spaces they have left, carrying osteogenic cells - forms a primary ossification centre in the middle of the cartilage scaffold
- Elongation - new cartilage continues to form at the ends of the bones, increasing their length while the diaphyseal cartilage is being replaced with bone - turnover/treadmill process
What is the secondary ossification centre? What type of bone growth happens there?
Similar to primary centre of ossification - the secondary centre of ossification does the same for the cartilage of the epiphysis - Process of endochondral ossification
SOCs – secondary ossification centre - begin to form at or after birth in a predictable way. For example, on the right we can see the secondary ossification centres of the hip, with a small dot in the femoral head for a 4 month old and a much larger cenre in a 4 year old
Skeleton matures - primary and secondary centres fuse together to give the adult structure to the bone.
Note - second SOC in the greater trochanter of the bone, which is called an apophysis - site of ligament or tendon attachments - fuses to the bone in the second decade - source of avulsion fractures
Where is the physis located? What are some important structures in this zone?
The physis is the yellow and purple highlighted area with the secondary ossification centre in greeny-blue at the top and the metaphysis below
Another important feature….
Perichondrium, shown here in brown, which encircles the physis on its outer edge and consists of the perichondral ring and the ossification groove.
Ossification groove is an accumulation of chondrocytes involved in expanding the width of the physis
Outline the pattern of growth that occurs in a long bone - big picture
As physeal growth occurs, the epiphysis and physis migrate along the axis of the bone, pushing out the ossified bone of the diaphysis behind them - converyer belt
Outline the microscopic organisation of the physis - i.e. the different zones.
Resting Zone - sparsely packed chondrocytes
Proliferartive zone - chondrocytes mutiply and lining up in columns
Hyperthrophic zone - Increased cell volume
Metaphyseal bone - Bone formation
Note - cells remain stationary but the physis itself migrates pushing bone growth further
Outline what happens in the resting zone of the physis.
The first zone, by the epiphysis, contains sparsely packed chondrocytes - aren’t currently changing in size or producing matrix
Contain large stores of lipids, glycogen and proteoglycans for future growth and matrix production.
Outline what happens in the proliferative zone of the physis.
Upon stimulation - cells of the resting zone transition to become the proliferative zone and begin to stack up in columns and multiply at an increased rate.
Begin to produce the cartilaginous extracellular matrix, which has a similar structure to bone but without the calcium to make it rigid - occurs at the highest rate at the physis
Outline what happens in the hyperthrophic zone of the physis.
Hypertrophic zone - divided into 3 stages
1. Zone of maturation
2. Zone of degeneration
3. Zone of provisional calcification
As they are increasing in size, the chondrocytes are also collecting calcium and storing it to release upon their death
Relative weak point in the physis and is the site of slipped upper femoral epiphysis and Salter-Harris fractures
Outline what happens in the zone of maturation and degeneration in the physis.
Zone of maturation - where cells differentiate, and mature, slowly increasing in size until they’re twice as big as when they started.
Zone of degeneration - where the chondrocytes have a 5-fold increase in size, becoming almost too big to survive and undergo apoptosis
Outline what happens in the zone of provisional calcification in the physis.
Massive chondrocytes die and release the calcium they have stored up to calcify their surrounding matrix.
What is Achondroplasia - disease of the physis?
Normal trunk size but affects proximal limbs more than distal, ie humerus and femur are shorter than radius/ulna and tib/fib - rhizomelic Disproportionate dwarfism
What is gigantism - disease of the physis?
Gigantism occurs when an excess of growth hormone leads to increased proliferation of cells in the PZ of the physis and is almost always caused by a pituitary adenoma, innapropriately excreted the excess GH.
In adulthood - physes are closed - results in acromegaly where the hands, feet, forehead jaw and nose gradually increase in size.
