Bones, collagen, calcium, phosphate Flashcards
7 functions of the skeleton?
Raises us from the ground against gravity, determines basic body shape, transmits body weight, forms jointed lever system for movement, protects vitals structures from damage, houses bone marrow, mineral storage(calcium, phosphorus, magnesium)
Bone classification types by shape? (x5)
Long bones- tubular shaft with hollow shaft and ends expanded for articulation with others
Short bones- cuboidal in shape
Flat bones- plates of bones, often curved, protective function
Irregular bones
Sesamoid bones- round, oval nodules in a tendon
2 types of macro bone structures?
Cortical/ compact= dense, solid, only spaces for cell and blood vessels
Trabecular/ cancellous/ spongy= network of trabecular, bone marrow, cells and blood vessels
2 types of micro bone structures?
Woven= made quickly, disorganised, no clear structure Lamellar= made slowly, organised, layered structure
How does hollow long bone contribute to function? Trabecular bone contribute?Wide ends do what?
Keeps mass away from neutral axis, minimising deformation
Structural support while minimising mass
Spreads load over weak, low friction surface
What composition does bone have (%s)? Mineral and organic matrices provide what?
50-70%= mineral (hydroxyapatite, crystalline form of calcium phosphate)= stiffness 20-40%= organic matrix- collagen type 1 (90%)- elasticity, non-collagenous= 10% 5-10%= water
4 features about collagen? Type 1 found where? Type 2 found where? Type 3 found where?
Most abundant protein in body and ECM, found outside cells, tensile strength
3 cross linked PPCs in triple superhelical structures
Skin, ligament, tendon, bone
Cartilage and vitreous of the eye
Skin and during wound healing
Procollagen synthesised where? What repeat forms what shape? Y is often what? This increases what of collagen? Hydroxylation of proline requires what vitamin as a cofactor?
Inside the cell Gly-X-Y repeat--> helix Proline/ hydroxyproline Thermal stability of collagen Vitamin C
3 collagen molecules form what? Assembled into what? Held together by what? What is a component of the crosslinks? Breakdown by what?
Tropocollagen–> collagen fibril, covalent crosslinks from lysine/ hydroxylysine side-chains
Pyridinoline
Collagenases and cathepsin K
What is a primary bone?
Newly formed, poorly organised, may develop directly in a mesenchyme (intramembranous bone) e.g. vault of skull, lateral 1/3 of clavicle/ from hyaline cartilage proformer (endochondral bone)
What is a secondary bone?
Result of remodelling- original structure eroded and laid down in more organised way
Well organised
Compact (round edges of long bones) or cancellous (spongy)
Organised into osteons when thick
What does intramembranous bone formation involve?
Mesenchymal condensation (proliferation)—> osteoprogenitor cell differentiation–> osteoblast–> osteocyte
7 stages of endochondral ossification?
1) Cartilage proformer
2) Collar formation- of bone that surrounds central part of shaft
3) Invasion of osteogenic bud- blood supply
4) New osteoblasts form primary ossification centre@ centre of bone
5) Establishment of secondary ossification centres@ ends of bone
6) Lengthening via growth plates- epiphyseal plates of cartilage
7) Closure of growth plates- when primary and secondary growth centres fuse
GH stimulates growth of what in bone? Excess in children causes what? In adults causes what? Other hormones stimulators of bone growth?
Epiphyseal cartilage, children= gigantism, acromegaly
Sex hormones
Precocious puberty results in what? Hormone deficiencies cause what? Requirements for bone formation?
Reduced stature as growth plates close early
Tall stature- growth plates remain open for longer
Connective tissue, cells, calcium, phosphate
What is the modelling of bone? What is bone remodelling?
Gross shape is altered, bone added or taken away (growth, fracture, repair, mechanical adaptation)
All of the bone is altered, new bone replaces old bone, continuously remodelled at discrete sites in order to maintain integrity of the tissue
Osteoblasts are derived from what stem cells? Features of them? Secrete factors that do what?
Mesenchymal stem cells Basophilic Cuboidal- resting on bone Contain lots of RER Make osteoid- organic component, becomes mineralised after secretion by hydroxyapatite High alkaline phosphatase Regulate osteoclasts i.e. RANKL
Features of osteoclasts?
Monocyte lineage, multinucleate, high lysosome content, dissolve mineralised matrix, breakdown collagen, erode bone lie in Howship’s lacunae, high expression of TRAP and cathepsin K
Shape of bone lining cells? Derived from what? Features of osteocytes?
Flattened, derived from osteoblasts
Stellate, entombed in bone, trapped osteoblasts
Reasons for bone remodelling?
Form bone shape, replace woven bone with lamellar bone, reorientate fibrils and trabeculae in favourable direction for mechanical strength, response to loading, repair damage, obtain calcium
MSC progenitor cells contain SOX9 which are used to make what? IGF1 and fit D for what? Leptin used for what? As we age more mesenchymal progenitors are directed down what pathway?
Chondrocytes
Osteoblasts
Adipocyte
Adipocyte pathway
Bone lining cells are activated to form what? Make resorption pits containing what 2 things? Macrophages found@ site in what phase? Osteoblasts precursors are recruited and proliferate/ differentiate into what?
Osteoclasts
HCl- dissolves mineral, cathepsin K- digests matrix
Intermediate/ reversal phase
Mature osteoblasts- secrete osteoid which is mineralised–> new bone
What is coupling relating to bone formation? TGF-beta bound to what? Cleaved to TGF-beta by what? This along with what stimulates osteoblast recruitment, differentiation and activity?
Bone formation occurs at sites of previous bone resorption
Latency associated peptide- by H+ released by osteoclast
IGF1
What is balance when relating to bone formation? RANKL is essential for what? Osteoclasts are what?
Amount of bone removed by osteoclasts should be replaced by osteoblastic activity
OC formation, activation and survival
Specialised macrophages
What are hormonal mediators of osteoclast differentiation and activity? Paracrine/ autocrine mediators?
1,25- dihydroxyvitamin D, PTH/ PTHrP, oestrogen and leptin
Prostaglandins, interleukin- 1, interleukin- 6, tumour necrosis factor (TNF)
Mass of calcium in the skeleton? Mass in extracellular space? 3 ways distributed in the blood?
1200g, 1g
Ionised- metabolically active, important for cellular function: blood clotting, muscle contractility, nerve function
Complexed calcium
Protein bound calcium
At high pH (alkalosis), more calcium binds to what? This decreases what calcium type? First sign of this?
Albumin
Fraction of ionised calcium
Tetany- contraction of small muscles in hands and feet
How can calcium be released from bone? We absorb what % of dietary calcium? By what form? Amount per day? Come from what?
Released rapidly from exchangeable calcium on bone surface/ slowly by osteoclasts during bone resorption
30%- active in duodenum and jejunum, passive in ileum and colon
500-1500mg per day, dairy products, vegetables, cereals, oily fish
We absorb higher fraction of calcium when put on what diet?
Low calcium diet- mediated by calcitriol–> more calcium absorbed by active transport
Amount of Ca2+ by glomerulus depends on what? % of filtered usually reabsorbed? Most reabsorbed how and where?
GFR, ultra filtrable calcium (not protein bound)
98%
Passive transport in proximal tubule and loop of Henle
Small amount= in distal tubule due to high PTH
What % of filtered phosphate is usually reabsorbed? How and where? Regulated by what? Remainder reabsorbed where?
80%
Active transport in proximal tubule
Increased FGF-23 and PTH–> less phosphate reabsorption
Passively in distal renal tubule
Decreased serum calcium increases what hormone? What cells in PT gland have calcium sensing receptors on cell surface? PTH molecule quickly degrades into what? Small changes in serum ionised calcium result in what?
PTH- can be caused by increase in phosphate
Chief cells
PTH fragments= metabolically inactive
Big changes in PTH
Increased intestinal calcium absorption due to increased what? Known as what? Most made where due to what action? Converted into what in the liver? Small amount into what in the kidney? Increases when?
1,25 dihydroxyvitamin D
Calcitriol
In skin with action of UVB- small amount in diet
25- hydroxyvitamin D- most is excreted
1,25- hydroxyvitamin D
Increased PTH, decreased phosphate, calcium/ calcitriol levels
Calcitonin produced by what? Secretion stimulated by what? Effect of it?
C-cells in thyroid
Secretion stimulated by increased serum calcium
Lower bone resorption
Increased serum phosphate increases levels of what too? This decreases what and production of what?
FGF-23
Renal absorption phosphate and production of 1,25-dihydroxyvitamin D–> decrease phosphate and calcium absorption
Bone mass increases until what age? The decreases what % per year? Faster for who?
Age 30
1% per year
Post-menopausal women
What does exercise result in in the skeleton?
Changes to mass and architecture without changing material properties (architectural changes can alter strength without changing mass)
Skeleton’s response to exercise is what type of effect? Force/ deformation leads to what? Strain is equal to what?
Direct and site-specific
Strain (SL)
SL/ ratio of deformation to original length
How does increased activity affects strains and therefore mass? Decreased activity?
Increased activity–> increased strains–> increased mass
Decreased activity–> decreased strains–> decreased mass
What variables can affect strain? Not the same in different what? What is the mechanostat model?
Magnitude, rate, frequency, dwell (hold/ rest periods), number of cycles
Different sites, different sexes and different ages
Bone growth and bone loss is stimulate by the local mechanical elastic deformation of bone
What do bones respond physiologically to?
Occasional high magnitude, high rate events- can strength train but not endurance train your skeleton
What is a fracture? When do they occur?
A breach in continuity of bone.
When non-physiological loads are applied to normal bone and physiological loads applied to abnormal bone.
Fractures in abnormal bone due to what? What are the 4 fracture healing stages and how long does each last for?
Tumours, metabolic bone disease.
Haematoma(hours)–> inflammation(days)–> repair(weeks)–> remodelling(months to years)
What occurs during haematoma of a fracture? What happens during inflammation of a fracture? What do haematopoietic cells do in inflammation? What do osteoclasts do? What do mesenchymal stem cells do?
Bleeding, decreased blood flow, periosteal stripping, osteocyte death.
Fibrin clot organisation- platelets rich in chemo-attractants, neovascularisation, cellular invasion
Clear debris, express repair cytokines
They resorb dead bone
Build cell for repair
What happens during the repair of a fracture? What do fibroblasts, chondroblasts and osteoblasts form?
‘Callus’ formation
Fibroblasts= fibrous tissue, chondroblasts= cartilage, osteoblasts= osteoid.
Progressive matrix mineralisation
High vascularity
What occurs during remodelling of bone?
Woven bone is replaced by lamellar bone
Increased bone strength, vascularity returns to normal, healing without scar- unique
3 principles of fracture management? 5 types of fracture fixation?
Reduce(the fracture)–> immobilise (the part)–> rehabilitate(the patient)
Slings, casts and splints, extra-medullary devices, intra-medullary devices and external fixation
Factors that influence fracture healing?
Patient- age, nutrition, smoking, drugs- NSAIDs, steroids
Tissue- bone type: cancellous vs. cortical, bone site: upper limb vs. lower limb, vascularity/ soft tissue damage, bone pathology, infection
Treatment- apposition of fragments, stability, micro motion
What does frailty mean? What can it be used to predict?
Weak physiological and psychological states
Morbidity, health service used, institutionalisation and mortality
What does cardiovascular deterioration involve?
Central and peripheral arteries thicken with age; atherosclerosis= severe
Stiffening of arterial walls, increase in pulse wave velocity, increase in systolic BP, increase in left ventricular wall thickness of 30% between ages of 25 and 80 years
Most useful overall measure of cardiac performance? Most common causes of stroke? Why does respiratory capacity reduce?
Cardiac output
Thrombotic/ embolic occlusions (clots within and outside the brain)
Decrease in elasticity, alveolar diameters widen and alveolar surface area per unit of lung volume decreases
How does cognition decrease with age?
Speed and capacity of various forms of memory and cognitive processing decrease with age
What is episodic memory?
Encoding, storage and retrieval of personally-experienced events- involves long-term and working memory. Processing capacity appears to decline more than long-term memory with increased age.
What is generic memory?
Repository of knowledge stored without reference to the context in which it was acquired.
Most prevalent causes of physical frailty at greater ages?
Many cancers, atherosclerosis and heart disease, Arthritis Diabetes Decreased respiratory capacity Decreased muscle strength Decrements in sight Decrements in hearing
