MSK💪🩻🦴 Flashcards

Question

Bone modelling

Answer 1

Gross shape is altered, bone added or taken away

Answer 2

All of the bone is altered, new bone replaces old bon

Answer 3

- Form bone shape - Replace woven bone with lamellar bone - Reorientate fibrils and trabeculae in favourable direction for mechanical strength - Response to loading (exercise) - Repair damage - Obtain calcium - Dysregulated remodelling = disease!

Answer 4

0-20 -> development -> modelling 20-50 -> maintenance -> remodelling 50+ -> osteoporosis -> acquired pathology

Answer 5

Periosteum tears Haematoma Adjacent bone cell death Soft tissue damage Callus Osteoblasts -> new woven bone Osteoclasts -> mop up dead bone, remodel strong bone Osteoblasts lay down lamella bone

Answer 6

Anti-catabolic- stop osteoclasts (more) Anabolic- stimulate osteoclasts

Answer 7

modular building block (3 residues per turn) up to about 1000 amino acids X and Y are often proline, hydroxyproline or hydroxylysine Allows the formation of a helix (alpha-chain)

Answer 8

3 collagen chains – 2 x α1 + 1 x α2 Form the 3-stranded tropocollagen molecule

Answer 9

The tropocollagen modules are then assembled into a collagen fibril The tropocollagen molecule and the fibril are held together by covalent crosslinks (both intraand intermolecular) derived from lysine/hydroxylysine side-chains

Answer 10

N terminals and c-terminals are cut off the ends N creates P1NP C creates P1CP Can be measured

Answer 11

Covalent crosslinks Hydrogen bonds Intermolecular crosslinks

Answer 12

– Within and between the triple helix/tropocollagen molecule = “intra/intermolecular crosslinks” – OH-lysine x2 lysyl oxidase needs copper

Answer 13

– Between hydroxyproline molecules, within tropocollagen * OH-proline from proline requires Fe2+ * Fe3+ to Fe 2+ requires vitamin C

Answer 14

– = “intermolecular crosslinks” - – OH-lysine x 3 = pyridinolines

Answer 15

Via proteinases esp. collagenases and cathepsin K (in bone) Can be a normal process of repair and replacement (breakdown is balanced by synthesis), or pathological process - examples: arthritis, osteoporosis, tumour invasion, hypertrophic scarring, kidney fibrosis

Answer 16

NTX and CTX Can be measured to see breakdown

Answer 17

– Type I – bone, tendon, ligaments, skin – Type II – articular cartilage, vitreous – Type III – alongside Type I – wound healing – Type IV - basal lamina – Type V – cell surfaces – Type X – growth plate

Answer 18

* Synthesised by osteoblasts * 90% collagen * Other proteins * osteocalcin, osteonectin, osteopontin, fibronectin, bone sialoprotein, bone morphogenetic proteins (BMPs)… * Contribute to structure * Regulate bone cell activity

Answer 19

* Alkaline phosphatase hydrolyses pyrophosphate * Inorganic phosphate complexes with calcium to form hydroxyapatite * Hydroxyapatite crystals propagate along collagen

Answer 20

*Skull *Clavicles

Answer 21

Chondrocytes become hypertrophic which attracts blood vessels and so osteoblasts which form the bones

Answer 22

Driven by oestrogen

Answer 23

Outward growth of bone Osteoblasts on osteocortical surface add on bone going outwards Osteoclasts add on bone growing inwards

Answer 24

About age 25

Answer 25

Alkaline phosphatase

Answer 26

*Skeleton is main reservoir o 1200 g *Extracellular space has much smaller amount of calcium (only 1 g), but it is key for o Muscle contractility o Nerve function o Normal blood clotting Total serum calcium usually about 2.4 mmol/L Ionised serum calcium about 1.1 mmol/L

Answer 27

*Ionised, metabolically active *Protein-bound, not metabolically active *Complexed, such as citrate, phosphate

Answer 28

At higher pH, albumin binds strongly to calcium

Answer 29

* Low ionised calcium is associated with contraction of the small muscles of the hands and feet o TETANY There is depolarization of the long nerves of the upper limb

Answer 30

* Major sources o Dairy products make up 2/3 − Milk, yoghurt, cheese * Minor sources o Vegetables, e.g. broccoli o Cereals, e.g. white bread o Oily fish, e.g. sardines

Answer 31

700 mg/day

Answer 32

*We absorb about 30% of dietary calcium o Active absorption in duodenum and jejunum o Passive absorption in ileum and colon *Higher fractional excretion when low availability o More active transport o Mediated by calcitriol, the active form of vitamin D

Answer 33

* Calcium can be released rapidly from exchangeable calcium on the bone surface o We don’t know much about this mechanism * Calcium can be released more slowly by osteoclasts during bone resorption

Answer 34

*The amount of calcium filtered by the glomerulus depends on o Glomerular filtration rate o Ultrafiltrable calcium − Ionised − Complexed * 98% of this filtered calcium is usually reabsorbed o Reabsorption increased by PTH o Reabsorption decreased if the filtered sodium is high

Answer 35

Fractional excretion of calcium- 2% Fractional excretion of phosphate- 10%

Answer 36

4 parathyroid glands express calcium sensing receptor Decrease in serum calcium means increase in parathyroid hormone

Answer 37

Small changes in serum ionised calcium Big changes in PTH

Answer 38

Increase Ca2+ Reabsorption Increase Phosphate reabsorption Increase 1 α - hydroxylation of 25-OH vit D Bone Remodelling Bone resorption > bone formation No direct effect increase of ca2+ absorption because of increased 1,25 (OH) 2 vit D

Answer 39

Increased gut ab

Answer 40

* Hormone produced by thyroid C cells (parafollicular cells) *Secretion stimulated by increased serum calcium * Its effect is to lower bone resorption *Significance in humans uncertain o It is much more important in animals living in a high calcium environment, e.g. fish

Answer 41

Forms from 7-dehydrocholesterol Synthesised in the skin To maintain vitamin D must expose arms for 20mins/day in good sunlight

Answer 42

7- dehydroxy cholesterol in skin -> 25 hydroxy D in liver-> 1,25 hydroxy D in kidney Calcitriol is the active form of vitamin D and it is hydroxylated at positions 1 and 25

Answer 43

* VDR, vitamin D receptor * TRPV6, transient receptor potential V6 * PMCA, plasma membrane calcium pump ATPase

Answer 44

ATP DNA cAMP Phospholipid bilayer Bone mineral – calcium hydroxyapatite

Answer 45

* Whole body phosphate 500 - 800g * 1% total body weight * 90% in bone mineral * Serum phosphate 0.8 – 1.5 mmol/l

Answer 46

* Poor bone mineralisation * Rickets or osteomalacia * Pain, fractures

Answer 47

* Excessive formation of hydroxyapatite * Deposition in tissues other than bone e.g artery calcification and tumoral calcinosis

Answer 48

- Protein * Animal * Dairy * Soy * Seeds and nuts - Adult recommended daily intake = 700mg

Answer 49

In glomerulus unbound phosphate (about 90%) is filtered 80% reabsorbed in PCT- Na cotransporter 10% reabsorbed in the distal tubule Maximum rate of reabsorption is limited, so excess is excreted

Answer 50

* Parathyroid hormone * 1,25 dihydroxyvitamin D * FGF-23

Answer 51

Main function is regulation of calcium Also affects phosphate Increases 1,25 vitamin D Increases active gut absorption Decreases tubular reabsorption of phosphate Increases renal excretion

Answer 52

Now known to be the major regulator of phosphate metabolism * Produced by osteocytes * In response to: * Rise in phosphate levels * Dietary phosphate loading * PTH * 1,25 vitamin D

Answer 53

* Presents in childhood or adulthood * Bone pain, deformity, fracture * Low bone density * Low serum phosphate * High urine phosphate * X-linked hypophosphataemic rickets (XLH) * Autosomal dominant rickets (ADR)

Answer 54

* Linkage analysis * Fixed genetic markers * Identify on which chromosome and region the abnormal gene is likely to be * Sequencing * Identify where DNA differs between affected and unaffected people White Nature Genetics 2000 Named FGF-23 because sequence similar to other FGFs

Answer 55

* Rare form of osteomalacia with low phosphate * Seen in patients with small benign mesodermal tumours * Osteomalacia heals when tumour removed

Answer 56

* Decreases expression of Na transporter in the renal tubule * Increases renal excretion of phosphate * Decreases 1α-hydroxylation of vitamin D * Decreases gut absorption of phosphate * Decreases whole body phosphate

Answer 57

* Calcium mostly regulated by hormones that increase serum calcium * PTH, vitamin D * Phosphate mostly regulated by hormones that decrease serum phosphate * FGF-23, PTH

Answer 58

* Osteoblasts and osteoclasts must be able to communicate with each other. * Coupling o Bone formation occurs at sites of previous bone resorption * Balance o Amount of bone removed by osteoclasts should be replaced by osteoblastic activity

Answer 59

Macrophages ("big eaters", makros = large, phagein = eat) Involved in chronic inflammation Phagocytose (ingest) pathogens Osteoclasts are specialised macrophages

Answer 60

o A group of proteins and peptides that are used to allow one cell to communicate with another. o Released by many types of cells (both haemopoietic and non-haemopoietic) o Particularly important in immune responses (immunological, inflammatory and infectious diseases). o Sometimes these effects are strongly dependent on the presence of other chemicals and cytokines * The cytokine system demonstrates great redundancy and great pleiotropism.

Answer 61

Redundancy means that most functions of cytokines can be performed by many different cytokines. o Blocking or genetically ablating ("knockout" transgenic technology) a particular cytokine rarely has widespread or dramatic effects

Answer 62

* Pleiotropism means that a single cytokine has many different functional effects, on many different cell types or even on the same cell. o Overexpression or exogenous administration of a single cytokine frequently has several diverse effects.

Answer 63

* Hormones (endocrine) including o 1,25 dihydroxyvitamin D o PTH/PTHrP o Oestrogen o Leptin * Paracrine/autocrine including o Prostaglandins o Interleukin-1 (IL-1) o Interleukin-6 (IL-6) o Tumour necrosis factor (TNF)

Answer 64

* None of them appeared to have significant effects through receptors on osteoclasts! * They didn’t work in pure osteoclast cultures * They only worked in the presence of osteoblasts or other bone marrow stromal cells (mesenchymal lineage)

Answer 65

* Also known as osteoclastogenesis inhibitory factor (OCIF) * A member of the tumour necrosis factor (TNF) receptor superfamily. * Inhibits the differentiation of myeloid precursors into osteoclasts * Decreases resorption by osteoclasts in vitro and in vivo. * Works by binding to RANK-ligand, thus blocking the RANK-RANK ligand interaction between Osteoblast/Stromal cells and Osteoclast precursors

Answer 66

Mesenchymal stem cells * Can give rise to o Osteoblasts o Adipocytes o Chondrocytes o Myocytes * As we age, more mesenchymal progenitors are directed down the adipocyte pathway

Answer 67

Increases rank ligand and OPG Increased osteoblast activity in prostate cancer

Answer 68

* Sclerostin (Scl), like Wnt, is a secreted glycoprotein. * Sclerostin deficiency associated with increased Wnt signalling * Increased bone formation * Decreased bone resorption * Anti-sclerostins should have anabolic effects on bone

Answer 69

Produce movement Support soft tissues Maintains posture and body position Communication Control openings and passageways Control of body temperature Breathing via diaphragm

Answer 70

Responsiveness (excitability)- capable of responding to stimuli Conductivity- local electrical change triggers a wave of excitation' Contractability Extensibility Elasticity- returns to resting position

Answer 71

Sarcolemma invaginations that help propagating an action potential

Answer 72

Length 5cm Diameter 100um

Answer 73

Light band- I-band, actin, divided by Z-disc Dark band- A-band, overlapping of actin and myosin, divided by M-line

Answer 74

Contains F-actin capped by alpha actinin and CapZ and tropomodulin. Nebulin consists of 35aA acting binding motifs and acts as a molecular ruler

Answer 75

Contains myosin filaments maintained by Titin which acts as a molecular spring. Titin is the largest protein in our genome with >34000aA

Answer 76

Each thick filament contains approx 300 myosin heads Each head cycles 5 times/second

Answer 77

1. ATP binds to the myosin head cauring the dissociation o f the actin myosin complex 2. ATP

Answer 78

Motor neurones send an impulse to muscle which communicates via a neuromuscular junction

Answer 79

A motorneuron and all fibres innervated by it A motor unit always contains fibres of the same type (slow/fast)

Answer 80

ACH stimulates acteylcholine gated cation channels w

Answer 81

Troponin C binds to Ca2+ Troponin I is an inhibitory subunit Troponin T binds to tropomyosin

Answer 82

Rods cover 7 myosin binding sites on the actin and prevents binding Binding of Ca2+ to the troponin binding sites which pulls it away from the binding sites

Answer 83

Fatigue resistant Red- myoglobin Low glycogen content Oxidative Aerobic atp synthesis High mitochondria SOleus

Answer 84

Fatiguable White Glycolytic metabolism High glycogen content Anaerobic stp

Answer 85

Slow- half the diameter of fast fibres take longer to contract and

Answer 86

Creatine is ingested from the diat and transported to tge muscles biva the bloodstream 95% of creatune present in mysdls as P-creatine (60%) or creatine (40%)

Answer 87

Creatube c=kinase- cytoplasmic and mitochondrial isoforms

Answer 88

progeressive weakeness of the muscle# ATP shortage due to shortage of glycogen Lactic axid leveks rise and lover the PH which prevebnts normal workingin the sarcoplasm Failure of the neuromuscular junction

Answer 89

Structural classification Functional classification

Answer 90

fibrous Cartilaginous Synoial

Answer 91

Synarthroses- immovabkle and mostly fibrius Amphiarothese- slightly moveabke mostly carti Diarthroses- synovial k

Answer 92

Only sutures of skull Adjacent bines interdigitate Junction with very short tissue fibres

Answer 93

Bones connescted by a cord(ligament or interosseous membrane ofn ifbrous tissue Amount of mvmt permited is proportional to length of fibre E.g between radius and ulns

Answer 94

Peg in socket joint only found in tooth articulation

Answer 95

Bones connected bu hyaline cartilage Usually amphiarthroses e.g

Answer 96

Here the connecting cartilage is a pad or plate of fibrocartilage e.g pubic symphysis and intervertebral disk

Answer 97

Atriculating bines are separated by a fluid filled cavity most body

Answer 98

1. articular (hyaline cartilage 2. Joint capsule- inner layer is synovial membrane Joint synovial cavvity synovial fluid reinforcing ligamnets

Answer 99

Bursae- fluid filled sacs lined by synovial membrane Menisci- discs of fibrocartilage allow for friction free memt

Answer 100

Almost fricitionless resistes compressibve loads high water contednt low dcell contrent no blood supply

Answer 101

civers articykaitg surfaces with a thin fillm Modifird from pkasma by synovual membrana( synoviocytes) Fluid, proteins, charges sugars that bind water e,g hyaluronic acid Result: slimy fluid (loke eggwhite) Reduces friction during articulation

Answer 102

Sits on inside f joint capsule and encloses synivual cavity'inky a dw cels thich may have villi to increase SA

Answer 103

Ball and socket joint- knee Condyloid joints- metacarpal and phalanges Glifing joint- between carpals Hinge joint- elbow Pivot joint- between c1 and 2 Saddle joint-base of the thumb

Answer 104

Attatch bone to bone prevent excessive motion goide joint motion augemnt mechanical stbilty

Answer 105

Connect muscle to bone Transmit tenske loads form muscle to bone Prosuce joint torqu Stabilisis joint during oisometric contration ensbles joint motion siring isptonic stabilises

Answer 106

Clls fibroblasts 20% od tussye synthesis anr enremodle the ecm 80% ectracelllular matrix- 70% wet 30% solid spparselu vascularised

Answer 107

Collagen type 1 90-95% dry weight proteoglycan and ither types od collagen

Answer 108

fibres slighlt crimoed together allowing fir sime movement

Answer 109

influences elsasitn in tendons and ligaments little in tendons mroe in liagamebtum flavum

Answer 110

lower colagen content 90% of dry weight more elastin bllodd supply from isertion point fibres less organisd

Answer 111

Places of insertion of thendon or ligament into bone pain and proprioceptive receptors Important for disease e.g epicondyles of elbow achillies tehn

Answer 112

transmit forces tendos aee viscoelsasic- voth viscous and elastic can treform hsape themilw loads cause elongathom

Answer 113

1- toe regiom small loas and crimped fibres straighten 2. linear curve as fibres straigten and stifness increases rapide 3. pmax - maximal deformation ant tensile tstrength 4. yeild point- after which is complete failure to support structures

Answer 114

encapsuleated sensory recepotis proprioceptirs activated by stretch or active mucle contraction Associated intendons near insertion (mostly but also a nit in orougun'consists if thin capsule enclosing cillahem gibres

Answer 115

- maturation and ageing- up to 20 years aging preganancy and postpartuk physical training- increase tendon tensile strenght immobilisation decrease thensile strength

Answer 116

Only 59% of adults in England meet DoH recommended levels of PA ▫ 28% meet all aspects of guidelines * Drops to <10% in over 85s * 23% do <30 min exercise TOTAL per week * 5.3million 25-64 yo would find 3mph walk “vigorous” activity * Total cost of inactivity in UK >£20 billion/year

Answer 117

The ability of the circulatory and respiratory systems to supply oxygen to skeletal muscles and the muscles’ ability to absorb and utilise the oxygen, during sustained physical activity”

Answer 118

The condition of being physically fit and healthy

Answer 119

High uric acid levels in the blood cause urate/uric acid crystals to deposit in the joints. The crystals cause inflammation, which then causes the swelling, pain & redness. Toe is the most commonly affected joint

Answer 120

Poorly soluble in plasma The lower the pH the less soluble it becomes

Answer 121

Purines are in the blood (e.g Adenine and guanine + hypoxanthine and xanthine)

Answer 122

Diet Breakdown of nucleotides from tissues Synthesis in the body

Answer 123

Excreted in the urine Breakdown in the gut

Answer 124

Oestrogen helps to promote excretion of uric acid

Answer 125

Meat Offal – heart, liver & kidney Seafood - muscles Fish – herring and sardines Also – oatmeal, soya & yeast extracts Fructose – found in soft drinks

Answer 126

Metabolic syndrome Obesity Raised triglycerides Raised blood pressure Coronary heart disease Diabetes

Answer 127

Increases risk for CHD and gout combination of obesity raised triglycerides, raised blood pressure

Answer 128

Synthesis increased and excretion decreased Mainly beer, spirits and port wine Wine in moderation doesn’t increase risk of gout

Answer 129

Thiazide diuretics Low dose aspirin Ciclosporin Levodopa Ethambutol Pyrazinamide

Answer 130

Reduced kidney function can lead to reduced excretion of uric acid

Answer 131

Purines -----xanthine oxidase---> xanthine ---- xanthine oxidase -----> Uric acid

Answer 132

Damage to the joint (degenerative arthritis) Secondary infections Nerve damage

Answer 133

Consequence of high uric acid Urate crystals can form in the kidneys Causes damage to the kidneys & reduces kidney function

Answer 134

Increased tissue nucleotides and body purine nucleotides so increased purines and increased uric acid

Answer 135

- Rapidly growing malignant tissue - Leukaemia - Lymphoma - Polycythaemia rubra vera - Increased tissue breakdown - Tumour lysis syndrome - Trauma - Starvation - Psoriasis

Answer 136

Hypoxanthine & guanine are recycled back to precursors by enzyme HPRT. If enzyme missing leads to increased production of uric acid.

Answer 137

Bones protect the vital soft organs – brain, heart, lungs etc Bones allow muscles to work to move us around Bones store mineral and house marrow cells

Answer 138

Loading increases bone mass Off-loading decreases bone mass

Answer 139

Loading response is site-specific and localised

Answer 140

Deformation and strain Force (F) causes deformation ( change in length) Change in Length / Length femur: 600mm Deformation= 0.6 mm Strain = 0.6/600= 0.1%

Answer 141

Magnitude Rate (up and down) Frequency Dwell (hold/rest periods) Number of cycles

Answer 142

* Sex and age * Age * Hormones, cytokines * Drugs/medicines/nutraceutical

Answer 143

* There is not a single mechanostat * Our skeletons contain vast numbers of small units of bone, each of which has its own dynamically regulated mechanostat

Answer 144

* Bone responds maximally to only a few loading cycles each day * Exercise in the previous 4 hours increases the response to subsequent loading * Bone responds to very brief mechanical events (milliseconds) * Rest periods between single loading events (~10 seconds) increase their effect

Answer 145

Fluid flow shear stress Deformation of bone cause movement of fluid which signals the osteocytes The osteocytes then signal the other bone cells- extends processes to cells

Answer 146

Trabecular loss more pronounced for non load-bearing horizontal trabeculae

Answer 147

breach in continuity of bone Fractures occur when: non-physiological loads applied to normal bone Physiological loads applied to abnormal bone

Answer 148

Tumour -Benign -Malignant -Metastatic Metabolic bone disease -Osteoporosis -Paget’s Disease -Osteogenesis Imperfecta

Answer 149

Site Pattern Displacement / angulation Joint involvement Skin involvement

Answer 150

WHich bone Part of bone (prox., mid., or dist.)

Answer 151

Transverse Oblique Spiral Comminuted Segmental Avulsed Impacted Torus Greenstick

Answer 152

Displacement (%) Angulation – of distal part

Answer 153

Extra-articular Intra-articular

Answer 154

Open / closed Open fracture = breach in skin communicates with # Orthopaedic emergency Requires urgent treatment Soft tissue injury determines outcome

Answer 155

Epiphyses open and bone more ‘plastic’ ∆ fracture types Heal quickly  deformity remodelling

Answer 156

Haematoma (hours)-> inflammation (days) -> repair (weeks)-> remodelling (months to years

Answer 157

Bleeding endosteal and periosteal vessels, muscle etc Decreased blood flow Periosteal stripping Osteocyte death

Answer 158

Fibrin clot organisation Platelets rich in chemo-attractants Neovascularisation Cellular invasion Haematopoietic cells clear debris express repair cytokines Osteoclasts resorb dead bone Mesenchymal stem cells building cells for repair

Answer 159

‘Callus’ formation Fibroblasts produce fibrous tissue (high strain) Chondroblasts form cartilage (strain <10%) Osteoblasts form osteoid (strain <1%) Progressive matrix mineralisation High vascularity Soft callus 2-3 weeks Hard callus weeks to 5 months

Answer 160

Woven bone structure replaced by lamellar bone osteonal remodelling Increased bone strength Vascularity returns to normal Healing without scar - unique

Answer 161

Reduce fracture-> Immobilise the part-> rehabilitate the patient

Answer 162

Slings Casts and splints Extra-medullary devices plates and screws Intra-medullary devices nails External Fixation

Answer 163

Strain <2% Intramembranous Haversian remodelling Occurs with rigid fixation e.g plates and screws

Answer 164

Strain 2%-10% Responses in the periosteum and external soft tissues Endochondral healing Occurs with non-rigid fixation-casts

Answer 165

Semi-rigid fixation- i.m nail

Answer 166

Strain >10% Results in non-union

Answer 167

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 - # in metastatic deposit does not heal infection Treatment Apposition of fragments Stability (ability to resist force without deforming) Micromotion (<1mm)

Answer 168

Local- Vessel damage Nerve damage Compartment syndrome infection General- Hypovolaemic shock ARDS VTE Fat embolism

Answer 169

Local Malunion Non-union Avascular necrosis Ischaemic contractures Joint stiffness Myositis ossificans Complex regional pain syndrome Osteoarthritis General Poor mobility Functional disability and social isolation Pressure sores Disuse osteoporosis Loss of income / job

Answer 170

Axillary nerve

Answer 171

Deltoid and teres minor

Answer 172

Area at the top of the shoulder

Answer 173

Radial nerve

Answer 174

Wrist extension

Answer 175

Ulnar nerve

Answer 176

Altered abduction and adduction of fingers sensation to little finger and that part of hands