Musculo-Skeletal Flashcards
Myosin heavy chain isoform that splits ATP fastest supplying energy from glyolysis alone.
MHC 2B
high impact resistance training increases levels
Why are MHC 1 containing fibres “red”?
High myoglobin
low impact CV training increases levels –> fatigue resistance
How does the Growth Factor Endocrine Axis relate to muscle growth?
GH stimulates IGF-1 release from the liver.
IGF-1 activates satellite cells and protein synthesis leading to increased muscle filaments
NB: prolonged contraction releases IGF-1 from muscle (autocrine) to stimulate their own hypertrophy
Fill in the profile for a myopathy:
Weakness: Reflexes: Sensation: CK: EMG:
Weakness: proximal (from girdles) Reflexes: normal (unless severe wasting) Sensation: normal CK: raised EMG: more muscle recruitment to get certain force
Duchenne Muscular Dystrophy inheritance is …
Caused by a mutation in…this gene…
Onset age:
…X linked
…Dystrophin Xp21 gene…forms protein that links muscle cytoskeleton to the ECM
…3-5yrs
3 symptoms of DMD
- pseudohypertrophy of legs (scar tissue)
- Gowers manoevre and toe walking
- scoliosis
- cardiomyopathy, resp faliure
Difference between DMD and Becker’s MD?
DMD has a frameshift mutation, more severe.
Beckers is non frameshift so protein function is reduced but OK
2 Gene therapies for DMD
Ataluren - ribosomes cant bind to stop codon so its not read and protein is not truncated, better function
Eteplirsen - antisense oligon. for a specific exon 51 mutation, binds to RNA and restores reading frame so DMD –> Beckers.
Fill in the profile for a NMJ Disorder:
Weakness: Reflexes: Sensation: CK: EMG:
+feature
Weakness: proximal and extraocular muscles as smaller ratio of axon:muscle fibre
Reflexes: normal
Sensation: normal
CK: normal
EMG: amplitude of muscles AP reduces with repetitive stimulation
+fatiguability as Ach released from end plates is used up, takes time to replenish
What kind of condition is Myasthenia Gravis?
What is this condition associated with?
an aquired neurological autoimmune disease where the patient develops antibodies to Nic AchR on muscle membrane interferes with Ach action
associated with thymic abnormalities (thymus)
3 treatments for Myasthenia Gravis
-The enzyme Pryridostigmine which inhibits ACh-esterase so blocks ACh breakdown in cleft
Immunosuppresants e.g. azathioprine to reduce antibody and T cell functions
Thymectomy-removes driver of the autoimmunity
What does the botulism toxin do?
Stops Ach vesicles merging with the pre-synaptic membrane causing severe flaccid paralysis
What is Lambert Eaton Myasthenic Sydrome (LEMS)?
Antibodies to the VGCa2+C so no calcium can enter channel/no depolarisation –> flaccid muscle weakness
Fill in the profile for a Neuropathy:
Weakness: Wasting: Reflexes: Sensation: CK: EMG:
+feature
Weakness: distal (long ones more vulnerable)
Wasting: early and rapid (no regeneration signal)
Reflexes: reduced/absent
Sensation: abnormal
CK: may be elevated/notmal
EMG: particular neurogenic pattern
+feature: spontaneous fasiculations
How can pathological classifications of neuropathies as axonal or de-myelinating be done?
NCS-Nerve Conducting Studies
to see how fast the conduction is to see if Schwaan cells are affected.
Common Mononeuropathies:
- Median
- Ulnar
- Radial
- Common Peroneal
- Median-carpal tunnel
- Ulnar-handlebar
- Radial-sat night palsy-wrist drop
- Common Peroneal-foot drop
Inflammation, Guillan Barre Syndrome, brachial neuritis, diabetes, B12 deficiency, chemotherapy, alcohol, lead, leprosy and HIV are examples of causes of what?
Polyneuropathy
What is Charcot-Marie Tooth Disease?
CMTD is mostly AD length-dependent genetic condition.
Symptoms e.g. wasting of lower leg “champagme bottel-like”, pes callus/high arches, wasting of hand muscles.
At what levels does Erbs Palsy plexopathy damage the brachial plexus?
C5 and C6
Describe the most common cause of radiculopathy (nerve root)?
IV herniation, annulus ruptures and nucleus pulposus leaks out and compresses the motor root (can also be sensory root) leading to weakness (numbness if sensory)
Motor Neurone Disease is primary degredation in the..
It starts…
And affects…
..anterior horn of spinal cord
It starts…in one area e.g hand up arm to other then to face
And affects…all VOLUNTARY muscles
Explain the steps that occur at a skeletal NMJ leading up to sufficient AP to exceed threshold for contraction?
- AP conducted via motor nerves. Cause VGCC to open and Ca2+ influx -> Ach vesicle release
- ACh binds on LG-receptor, opens Na+. EJP.
If muscles stop producing enough force to support ‘x’, what happens?
- spindles in the muscles are stretched, signal sent up spinal cord
- increased MN excitation for muscle to contract more
What happens if you want to/voluntarily put ‘x’ down/stretch?
- brain signal to anatgonist’s muscle to contract (and a-MNs to agonist muscle inhibited)
- gamma MNs shorten poles so muscle is sensitive to stretch under the new tension
What is the purpose of the Golgi Tendon Organ?
-Ib afferents wrapped around collagen signal when the tendon is stretched/muscle contraction
What pattern is seen in LMN lesions?
Flaccid Paralysis:
- denervated muscle, weakness, wasting, areflexia
- fasiculations
What pattern is seen in UMN lesions?
Spastic Paralysis:
-weakness, hypertonia and hyper-reflexia
What are group II afferents involved in?
- slower, indirect connection to a-MNs
- respond to muscle length, maintain limb position and posture for resting muscle tone
What are group I afferents involved in?
- faster, monosynaptic connections to a-MNs
- respond to the rate of change/velocity of muscle
- correct rapid, unintended movements
Give 3 treatments that improve UMN damage by increasing spinal cord inhibition?
- oral benzodiazepines (boost GABAa inhibition)
- intrathecal baclofen (activates GABAa R on group I)
- intramusclular botox (weakens NMJs)
What is osteoarthritis a result of?
- Increased chondrocyte activity and matrix production in response to cartilage damage
- disrupts structure + abnormal collagen and proteoglycan structure
What is a BMEL?
How do they appear on X-Ray?
- Bone Marrow Oedema-Like Lesion (painful as richly innervated)
- end stage cyst seen as a shadow at edge of joint
What are aggrecanases and collagenases?
What endogenously inhibits them?
- MMPs-Matrix Metalloproteinases
- TIMPs inhibit their action
Give 2 inflammatory changes in Osteo Arthritis.
- lining cell hyperplasia
- increased vascularity
- subintimal fibrosis
What 3 areas are currently targeted for OA treatment?
- central pain processing e.g. amitryptiline
- DRG e.g. opiates
- OA joint e.g. corticosteroids, NSAIDS
Where does CT originate from?
What are its 4 classes?
Mesodermal origin
Proper (loose&dense), cartilage, bone and blood
How do proteoglycans lead to tugor?
They are negatively charged and v.hydrophilic, they bring in Na+ attracting lots of water via osmosis
Where are the following mainly found?
- collagen I
- collagen II
- collagen III
collagen I - bone
collagen II - hyaline cartilage
collagen III - woven bone
Give an example of a mutation in the following genes:
- collagen I
- collagen II
- collagen III
- collagen I - osteogenesis imperfecta (brittle, short)
- collagen II - achondrogenesis
- collagen III - Ehlers Danlos (hypermobile joints/skin..)
Elastin is arranged in ECM, made as tropo-elastin that polymerises to elastin. What is involved in its degredation?
- elastase degrades it
- a-1 anti-trypsin inhibits elastase
What is the elastin core covered in?
A sheath of microfibrils comprised of glycoproteins (mostly fibrilin)
What is crutis laxa?
Not enough elastin in skin
What is Marfan’s Syndrome a mutation in?
Fibrilin gene. Can get dilation of aorta and displacement of lens
What is a keloid scar a result of?
Too much collagen made
Bone marrow holds adipose tissue. What ion do the hydroxyapatite crystals hold?
Calcium
Osteoblasts lay down osteiod, what happens to them as the osteoid mineralises?
Osteoblasts become entombed between lamellae (layers of ECM) in lacunae where they mature into osteocytes which monitor minerals/proteins and regulate bone mass
How do osteoclasts (derived from MOs) reabsorb bone?
They release H+ ions and lysosomal enzymes
When is woven bone/1ry bone present?
In embryonic development
In fracture repair
What is the difference in woven bone and lamellar/2ndry bone?
Woven has osteoid (unmineralised ECM) and collagen is arranged randomly
Lamellar bone has organised sheets of strong mineralised osteoid. Can be outer compact bone or inner spongy bone.
The functional unit of Compact Bone (a type of lamellar bone) is an “osteon”. Name 3 features of it:
- lamellae in concentric circles surround a vertical Haversian canal
- Haversian canals are connected by horizontal Volkmanns canals
- osteocytes are located between the lamallae in lacunae interconnected by canaliculi (tunnels)
Spongy bone (aka cancellous/trabecullar) is light and porous but strong against multidirectional lines of force. What does this bone have?
- many large spaces, honeycomb like
- spongy lightness allows body to move
- 3D next work of fine columns cross linking to form irregular trabeculae.
- spaces between trabeculae often filled with marrow
