Muscle pathologies

Question 1

What are the 3 main types of human muscle tissue ?

Answer 1

1. Skeletal
2. Smooth
3. Cardiac

Question 2

What are the 4 characteristics of skeletal muscle tissue ?

Answer 2

They are voluntary, striated (due to sarcomeres), not branched, and multinucleated.

Question 3

What are the characteristics of cardiac muscle

Answer 3

• Involuntary
• Striated - due to sarcomeres
• uninucleated
• Have intercalated discs
• žGap junctions between cells

Question 4

What are the characteristic features of smooth muscle ?

Answer 4

• žCells not striated - No sarcomeres
• žSingle central nucleus
• Involuntary

Question 5

Describe the organization of skeletal muscle

Answer 5

Muscle fibres are the smallest contractile units , containing nucleii, mitochondria, sarcomeres

1. Each muscle fibre is covered by endomysium
2. 20-80 muscle fibres each surrounded by endomysium group together to form a facile which is encapsulated by perimysium
3. A large number of fasicles each encapsulated by perimysium group together and are covered by epimysium to form a muscle

Question 6

Describe the steps of excitation contraction coupling in skeletal muscle

Answer 6

1. Acetylcholine relased at neuromusclar junction
2. AP generated in response which goes down T-tubules of muscle cells
3. AP in T-tubules causes relase of Ca2+ from the sarcoplasmic recticulum
4. Ca2+ binds to tropnin on actin filaments
5. Tropomyosin is therefore physically moved aside to uncover cross-binding bridges on actin filament
6. Myosin cross-bridges attach to actin and bend pulling actin filaments towards the centre of sarcomere (contraction)
7. When no longer AP Ca2+ is taken back up in the sarcoplasmic recticulum
8. Ca2+ no longer bound to troponin, tropomyosin slips back to original postition over binding sites on actin, contraction ends, actin slides back to original resting place

Question 7

Describe the different areas of the sarcomere

Answer 7

Note sarcomere is the smallest functional unit of skeletal muscle

Sarcomere is located between the Z bands

Think IAHM

Question 8

Define what a fasciulation is and what they might occur in

Answer 8

• žVisible, fast, fine , spontaneous twitch
• žMay occur in healthy muscle – precitated by stress, caffeine, fatigue
• žOccur in denervated muscle which become hyperexcitable
• žUsually a sign of disease in the motor neurone , not the muscle

Question 9

What is myotonia ?

Answer 9

Is a symptom of a small handful of certain neuromuscular disorders characterized by inability to relax voluntary muscle after vigorous effort.

Question 10

What are the general symptoms/signs suggestive of muscle disease specifically ?

Answer 10

• žMyalgia (muscle pain)
• žMuscle weakness – often specific patterns of weakness depending on cause eg proximal limbs in polymyositis
• žWasting
• Hyporeflexia

Question 11

What is polymyositis and how does it typically present ?

Answer 11

An idiopathic inflammatory myopathy that causes symmetrical, proximal muscle weakness.

Typically presents with:

• Usually present with symmetrical, progressive (over weeks to months) proximal muscle weakness in the upper and lower extremities
• Commonly noticed as difficulty with particular activities e.g. climbing stairs
• Some have myalgia (muscle pain) or arthralgia (pain in joints)
• Dysphagia secondary to oropharyngeal and esophageal involvement occurs in about one third of patients with polymyositis
• Can also develop Interstitial lung disease

Question 12

What is dermatomyositis and how does it usually present ?

Answer 12

It is clinicaly similar to polymyositis so presents with the same symptoms but also has typical cutaneous manifestations

Typical cutaneous manifestations are:

• Heliotrope rash
• Gottons papules
• V-shaped rash over chest

Question 13

What age group does polymyositis and dermatomyositis most commonly affect ?

Answer 13

Usually above 20, esp aged 45-60

Question 14

Describe the pathogenesis of polymyositis (think this is the same for dermatomyositis also)

Answer 14

• It is a T-cell–mediated cytotoxic process directed against unidentified muscle antigens
• CD8 T cells, along with macrophages, initially surround healthy nonnecrotic muscle fibers and eventually invade and destroy them.

Question 15

What investigations are done to help diagnose polymyositis and dermatomyositis ?

Answer 15

• Inflammatory markers are often raised.
• Serum creatine kinase (CK) level is usually raised, often more than 10 times the normal level.
• Anti-Jo-1 and anti-SRP (these are the antibodies more specific to myositis)
• MRI may be useful to localize the extent of muscle involvement.
• Electromyographic (EMG) (abnormal in 90% of patients with it)
• Muscle biopsy is crucial in helping to diagnose polymyositis and in excluding other rare muscle diseases (believe this sounds the gold standard)

Question 16

What is their an increased risk of in patients with polymyositis and dermatomyositis ?

Answer 16

• There is an associated risk of malignancy. This is found in around 25% in patients and is greatest in the 5 years following diagnosis. Common cancers include breast, ovarian, lung, colon, oesophagus and bladder.
• Malignancy should be screened for at the time of diagnosis.

Question 17

What is the treatment of polymyositis?

Answer 17

Prednisolone (initially around 40mg) combined with immunosuppressive drugs such as methotrexate or azathioprine.

Question 18

What is inclusion body myositis ?

Answer 18

A degenerative (because little response to steroids) muscle disease characterised by slowly progressive weakness in 6th decade of life with characteristic thumb sparing

Question 19

Describe the typical presenting features of inclusion body myositis

Answer 19

IBM causes progressive weakness of the muscles of the wrists and fingers, the muscles of the front of the thigh, and the muscles that lift the front of the foot. Unlike in other inflammatory myopathies, the heart and lungs are not affected in IBM

Question 20

What is myotonic dystrophy ?

Answer 20

It is part of a group of inherited disorders called muscular dystrophies. It is the most common form of muscular dystrophy that begins in adulthood.

Question 21

Describe the typical features suggestive of myotonic dystrophy

Answer 21

• Characterized by progressive muscle wasting and weakness - typically distal-onset with weakness (hand/foot drop), weak sternomastoids, facial weakness and muscle wasting
• People with this disorder often have prolonged muscle contractions (myotonia) and are not able to relax certain muscles after use e.g. a person may have difficulty releasing their grip on a doorknob or handle
• Also, affected people may have slurred speech or temporary locking of their jaw.

Other signs include:

• cataracts
• Ptosis (drooping of eyelid)
• frontal balding in men
• cardiac defects

Question 22

What age does myotnic dystrophy usually present and state its inheritance pattern

Answer 22

• Autosomal dominant - žTrinucleotide repeat disorder affecting Cl- channels, with anticipation (affects people younger each generation)
• Usually affects people in their 20s/30s

Question 23

What are duchenne and bekers muscular dustrophies ?

Answer 23

They are part of a group of genetic conditions characterized by progressive muscle weakness and wasting

Question 24

What mutation causes duchennes and what causes bekers muscular dytrophy

Answer 24

Both are X-linked recessive conditions

• In duchennes the mutation results in dystrophin produced
• In bekers the mutation produces partially functioning dystrophin (hence symptoms are milder)

Both diseases caused by mutation in dystrophin protein – large deletion

Dystrophin allows connection between actin and myosin thus allowing muscle cells to renew and replace themselves

Question 25

Define myopathy

Answer 25

Myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness.

Question 26

Can females be affected by duchennes or bekers muscular dytrophy ?

Answer 26

Females are XX thus can be carriers and show symptoms of muscle weakness due to X inactivation

Question 27

Describe the typical disease progression in duchennes and in bekers muscular dystrophy

Answer 27

• In duchennes - usually affects boys in early childhood (3-4) symptoms progress rapidly and they are usually wheelchair dependent by adolescence and usually survive until 20s/30s
• The signs and symptoms of Becker muscular dystrophy are usually milder and more varied. In most cases, muscle weakness becomes apparent later in childhood or in adolescence and worsens at a much slower rate.

Question 28

What is death usually from in muscular dytrophies ?

Answer 28

Involvement of respiratory and cardiac muscles

Question 29

Describe the typical presentation of duchennes muscular dystrophy

Answer 29

• Usually slow to start walking (developmental delay) - gowers sign; boy lies on floor, asked to spring up as quickly as possible – uses hands to compensate due to muscle weakness
• Then presents with clumsy walking
• Tend to walk on their toes
• Calf hypertrophy - msucles are just big not strong tho
• Exaggerated lumbar lordosis

Question 30

Describe the typical presentation of bekers muscular dystrophy

Answer 30

Generalized weakness first affects muscles of the hips, pelvic area, thighs and shoulders. Calves are often enlarged

Essentially just a milder duchennes

Question 31

What may be raised on investigation which is highly suggestive of duchennes muscular dystrophy ?

Answer 31

CK - increased >40 times often

(think this will also be in bekers but more for duchennes)

Question 32

What other investigations can you do for muscular dustrophy ?

Answer 32

• Electromyography – EMG
• Muscle biopsy – stain for dystrophin gene – also see extensive granular degeneration
• Molecular genetic testing – screen for deletions

Question 33

What is rhabdomyolysis and what are some of the potential causes of it ?

Answer 33

• Damage to skeletal muscle causes leakage of large quantities of toxic intracellular contents into plasma such as - myoglobin, K+, PO₄3-, urate and CK,
• Many potential causes – crush injuries, falls and been left their for a while esp in older people (immobilisation), toxins, post convulsions, IVDU, burns, excessive exercise, compartment syndrome etc

Question 34

What is the classic traid of symptoms and what complications can develop in rhabdomyolsis ?

Answer 34

• žTriad of myalgia, muscle weakness and myoglobinuria
• Complications - acute renal failure and DIC

Question 35

On investigation what is suggestive of rhabdomyolsis ?

Answer 35

• CK raised often > 10000
• Negative troponin (MI excluded)
• visible myoglobinuria (tea or cola coloured urine)
• +ve blood in dipstick
• K+ and phosphate raised also

Question 36

Describe the MRC power grading of muscles

Answer 36

• ž0 – no movement
• ž1 – flicker of movement when attempting to contract muscle
• ž2 – some muscle movement if gravity removed but none against gravity
• ž3 – movement against gravity but not against resistance
• ž4 – movement against resistance but not full strength
• ž5 – normal strength

Question 37

Appreciate that some drugs and viruses can also cause myopathy

Answer 37