- increase vit D production via stimulating 1a-hydroxylase - increase ca absorption in DCT - increase phosphate excretion - stimulate resorption by increase CM-CSF + RANK in osteoblasts

MSK Flashcards by Elise Kim

3 type of joints

fibrous
cartilaginous
synovial

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structure/layout of cartilage

mainly made up of proteoglycans:
aggrecan = GAG + core protein

they produce high osmotic pressure –> inflating the cartilage –> high gel swelling pressure

many proteoglycans held via hyaluronan

these are held by collagen type II

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what cell secretes lubricin and hyaluronan

type B synoviocyte cell

lubricin - for high load low velocity
hyaluronan - for low load high velocity

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what cell is osteoclasts and osteoblasts differentiated/derived from

osteoclasts = haematopoietic
osteoblasts = mesenchymal (but also can be from haematopoietic)

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describe how PTH stimulates resorption of bone

PTH receptors on osteoblasts

osteoblasts produce RANK ligand

RANK receptors on osteoclast PRECURSORS

stimulates differentiation into osteoclasts –> resorption

osteopotegrin binds to RANK ligand = antagonist

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what do osteoblasts and osteoclasts produce

osteoblasts = uOCN

stimulates b-cells (Pancreas)
Increase insulin
increases glucose uptake for energy for bone growth

osteoclasts = FGF-23

acts on kidney
increases phosphate excretion
decreases 1a-hydroxylation = dec. vit D function

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how is PTH produced

in parathyroid gland by chief cells

pre-prohormone–> ER—> prohormone–> golgi–>released into circulation–> hormone–> broken down in blood–> 1-34 is active

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PTH function

increase vit D production via stimulating 1a-hydroxylase
increase ca absorption in DCT
increase phosphate excretion
stimulate resorption by increase CM-CSF + RANK in osteoblasts

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describe function of CaSR

calcium sensing receptors on chief cells of parathyroid gland
when ca rises

Gi —> decrease PKA –> decreases PTH
Gq–> DAG/IP3–> increases PKC and Ca–> decreases PTH

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synthesis of vitamin D

cholesterol —–> cholecalciferol (D3) when light hits skin
ergosterol —–> ergocalciferol (D2) from diet

these go to liver –> 25-OH—> kidney —> 1a-hydroxylase–> 1,25 triol

(1a-hydroxylase stimulated by PTH and inhibited by FGF23)

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what type of receptor does vitamin D bind to

type 2 nuclear

binding = dimerisation with retinoic acid receptor

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describe how production of vitamin d leads to its own negative feedback inhibition

increases Ca –> decreases PTH–> decreases 1a-hydroxylase

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transport of calcium in gut (2 ways)

paracellular route

2. TPRV –> calbindin–> Ca/3Na or CaATPase

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does vitamin D increase or decrease insulin resistance when acts on pancreatic cells

decrease

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how many somites formed in humans

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what are somites formed from

presomitic mesoderm

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what do somites differentiate into and what do they form (4)

1) dermamyotome + sclerotome
2) myotome + dermatome + sclerotome
3) syndetome

sclerotome = vertebrae
myotome = epimere(extensor of vertebral column)/hypomere(chest wall + limb muscles)
dermatome = dorsal dermis
syndetome = tendons

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3 tiers of control of somitogenesis

1) bottom = within cell (time for transcription etc.)
2) middle = between cells (delta-notch signals)
3) top = cranial+caudal ends (cranial -retinoic acid + caudal - wnt+FGF)

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what bones do not undergo endochondrial ossification

flat bones of face
cranial bones
clavicle

they undergo intramembranous ossification

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explain how symmetry and elongation of limb muscles are controlled

FGF from apical ectodermal ridge = keeps the zone of proliferation from differentiating = elongates

SHH from zone of polarising activity controls the symmetery of AER

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explain myotome —> myofibre

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myotome—-myf5/myoD—-> myoblast—myogenin—-> myotubes (primary and secondary –mrf4—> myofibre

what is secreted from growth cone for a NMJ to form

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agrin

acts as a signal by binding to MUSK (tyrosine-kinase receptor) on myofiber

what is Duchenne muscular dystrophy

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mutated dystrophin gene (responsible for connecting sarcomere with sarcolemma = muscle integrity)

due to frameshift deletion

risk of death
but satellite cells are not affected

oestrogen effect on bone

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inhibits osteoclasts

therefore as you age, decrease of oestrogen, more osteoclasts resorbing = osteoporosis

localised = paget’s

what is osteomalacia

lack of vit D--> lack of absorption of calcium --> weak/undermineralised bones in children = rickets

4 stages of fracture healing

1. inflammation 2. soft callus 3. hard/bony callus 4. bone remodelling

treating gout (inflammatory mono)

1) treat acute attack - NSAIDs - colchicine - steroid 2) prevent - reduce serum uric acid below crystallising threshold - xanthine oxidase inhibitors - uricosuric drugs

what joints are affected in RA vs osteoarthritis

RA = PIP/wrist/MCP OA = DIP/1st CMC joints

what gene can cause ankylosing spondylitis(arthritis affecting spine)

HLA B27+

3 types of hyperparathyroidism

primary - high ca/PTH due to tumour causing high production of PTH secondary - low Ca so you get high PTH tertiary - after secondary when you get a transplant so high ca due to high PTH that body is used to

what is probably the cause if there is low PTH but high Ca

cancer--> inflammatory response--> mediators--> stimulate osteoclasts--> high resorption of Ca granulomatous disease (granulomas contain 1a-hydroxylase--> stimulates vit D)

treatment for hypercalcaemia

- hydrate with saline (stimulates 3Na/Ca) - loop diuretics (furosemide) to help pee/flush out ca - bisphosphonates (stops osteoclasts) - calcitonin (only hormone to decrease calcium levels) - prednisolone (steroid to suppress immune response) - calcimimetics to activate CaSR to decrease PTH - surgery to remove parathyroid tumour (primary)

2 types of hypoparathyroidism

primary = congenital/autoimmune causing faulty production from parathyroids secondary = due to injury/surgery

why might you get low calcium despite having high PTH

pseudoparathyroidism | PTH receptors are not working

gene therapy option for Duchenne

ataluren - stop codon read through eteplisren - antisense oglionucleotide for exon 51 (specific)

what degrades joint tissue

aggrecanase MMP their products (bind to TLR4) cause positive feedback to keep degrading

what is the extracellular matrix made up of

ground substance fibrous proteins (collagen/elastin from fibroblasts) water minerals

how is elastin formed

tropoelastin----polymerisation--> elastin laid down due to microfibrils composed of fibrilin

what is elastin degradation controlled by

elastase = degrades alpha 1 anti-trypsin = inhibits elastase = prevents degrading

what is pulmonary emphysema and Marfan syndrome

PE = lack of anti-trypsin so elastase degrades elastin MS = mutation of fibrillin gene so elastin not deposited properly

what type of collagen causes the conditions: - osteogenesisimperfecta (glycine >taurine disrupts alpha helix) - achondrogenesis (lack of ossification) - ehlers-danlos syndrome

- type I (bone/tendons) - type I - type III/V (skin/blood vessels)

what can muscle fibre number be affected by

fibre # is set from birth but it can be affected by temp/nutrition/hormones/ innervation

4 main myosins

type 2 = fast - IIx - IIalpha - IIbeta type1 = slow -beta-slow

4 types of pseudo hypothyroidism

(all have high PTH levels) 1a - low urine cAMP / clinical phenotype 1b- low urine cAMP / non-clinical phenotype 1c - normal cAMP/ clinical phenotype 2 - normal cAMP / non-clinical phenotype

4 types of pseudo hypothyroidism

(all have high PTH levels) 1a - low urine cAMP / clinical phenotype 1b- low urine cAMP / non-clinical phenotype 1c - normal cAMP/ clinical phenotype 2 - normal cAMP / non-clinical phenotype phenotype = - short 4th/th metacarpals - round/obese face - ecptopic calcification - short - reduced IQ - issues w/ pituitary hormones

what are looser zones

pseudo fractures that don't penetrate the whole way through

difference between myasthenia graves and botulism

both cause muscle weakness / NMJ disease MG - Ach nic receptors are blocked by autoantibodies botulism - prevention of release of Ach from synaptic vesicles

mononeuropathy vs radiculopathy

focal pattern of neuropathy ``` mono = affecting 1 nerve radiculopahty = nerve root ```

organisation of collagen fibres in tendons/ligaments, bone and cartilage

tendons and ligaments (I) = parallel bone (I) = spirals cartilage (II) = meshwork

pulmonary emphysema and Marfan syndrome

PE = lack of anti-trypsin---> high elastase activity Marfan = mutation of fibirillin = can't lay down elastase --> fragile tissue/unstable joints

what occurs during hypertension in terms of elastin/collagen

increased synthesis and deposition ---> - thicker vessel walls - reduced vessel diameters - slower turnover of elastin/collagen

MSK Flashcards

(51 cards)