EXAM 1 Skeletal Muscles I

Question 1

What is the structure of the skeletal muscle?

Answer 1

Muscle -> bundle of muscle fibers -> muscle fiber -> myofibril -> actin & myosin

Question 2

What is contracting unit that is made up of myosin and actin?

Answer 2

Sacromere

Question 3

An action potential travels along a motor nerve to its endings on a muscle fiber. What is this junction called?

Answer 3

Neuromuscular Junction (NMJ)

Question 4

What is the function of a T tubule?

Answer 4

It carries the impulse to the muscle cell.

Question 5

Initiation of muscle contraction involves entry of what cation? via what voltage gated channel?

What neurotransmitter is released after the entry of above cation?

Answer 5

Ca2+ via voltage gated Ca2+ channels

Achetylcholine (Ach)

Question 6

Release of Ach into the synapse opens multiple Ach-gated channels on the postsynaptic muscle membrane (aka _____ ). This allows large quantities of ______ to diffuse into the interior of the muscle fiber membrane.

Answer 6

sarcolemma; Na ions

Question 7

Entry of Na ions into the muscle fiber membrane causes local ______ that leads to opening of more voltage gated _____ channels. This initiates the action potential at the myofibril membrane (aka _____).

Answer 7

depolarization; sodium; sarcolemma - just making sure!

Question 8

As the action potential depolarizes the sacrolemma, it causes the _______ to release large quantities of ______ that was stored in the above blank.

Answer 8

Sacroplasmic reticulum; Ca

Question 9

Ca ions initiate attractive forces between ____ and ____ causing them to slide alongside each other. This is known as the ______ process.

Answer 9

actin filaments; myosin filaments; contractile process

Question 10

After a fraction of a second, the ____ ions are pumped back into the _______ ______ by a _______ pump where it is stored until a new muscle action potential starts.

Answer 10

Calcium; sarcoplasmic reticulum; Ca++ membrane pump

Question 11

What do you know about troponin?

Answer 11

Troponin is a protein that binds to actin. During a MI it is released into the blood which is why someone suspected of a heart attack gets troponin levels checked.

Question 12

What clusters of receptors located on the sarcolemma are responsible for INITIATION of signals leading to muscle contraction?

Answer 12

Acetylcholine receptors (AChR)

Question 13

Common symptom that is a result of impaired function at the NMJ?

Answer 13

painless weakness

Question 14

This is an autoimmune disease due to autoantibodies directed against the muscle receptor for Ach (on the postsynaptic sarcolemma).

Answer 14

Myasthenia Gravis

Question 15

What is the mechanism for Myasthenia Gravis?

Answer 15

Autoantibodies block the muscular achetylcholine receptors (AchR) so Ach cannot bind and depolarization won’t take place. Eventually the AchR are down regulated. So with repeated stimulation muscle weakness worsens.

Question 16

What are symptoms of Myasthenia Gravis?

Answer 16

1) fluctuating weakness that worsens with exertion
2) diplopia (double vision) and ptosis (drooping eye lids)
3) generalized weakness

Question 17

If Myasthenia Gravis is due to bad antibodies, what other organ could be at fault?

Answer 17

Thymus: supposed to produce antibodies that are nonreactive to self. Thus a thymus disorder (thymoma) could cause normal antbodies to attack the body. i.e. myasthenia gravis or lupus.

Question 18

What is an antibody-mediated disease of the NMJ that blocks Ach release from the presynaptic nerve ?

Answer 18

Lambert-Eaton Myasthenic Syndrome (LEMS)

Question 19

What is the mechanism for LEMS?

Answer 19

Antibodies block presynaptic Ca channels so Ach is not released.

Question 20

Patients with LEMS typically present with _______ of their extremities. In contrast to MG, rapid repetitive stimulation ______ muscle response.

Answer 20

weakness; increases i.e. weakness improves upon activity!

Question 21

LEMS is linked to what type of cancer?

Answer 21

Small cell lung cancer

This is because the body makes nonspecific antibodies that attack Ca channels on both cancer cells and normal cells.

Question 22

What is the difference between LEMS and MG?

Answer 22

LEMS: antibodies against NERVE releasing Ach, starts at extremities and moves UP, weakness IMPROVES upon activity, small cell lung cancer

MG: antibodies against Ach MUSCLE Receptor, starts at eyes and moves DOWN, weakness WORSENS upon activity, thymoma

Question 23

Name 2 muscular disorders caused by Toxins and how they work.

Answer 23

1) Botulism aka Botox: caused by Clostrodium botulinum that blocks release of Ach from presynatic neurons.
- causes hypotonia in babes! “floppy baby”

2) Curare - muscle relaxant that blocks Ach receptor resulting in flaccid paralysis.

Question 24

What are muscle stem cells that help in muscle regeneration as long as there is a balance between regeneration and destruction?

Answer 24

Satellite cells

Question 25

What is type I myofibers?

Answer 25

They are slow reach fibers, not exhausted easily (running a marathon), "slow low power"

Question 26

What is type II myofibers?

Answer 26

They are fast reaching fibers, can give so much force/ strength but easily exhausted (sprinter), "fast high power"

Question 27

This is the result of loss of innervation, disuse, cachexia (wasting of the body), old age, and primary myopathies.

Answer 27

Skeletal muscle atrophy Loss of muscle mass = severe atrophy

Question 28

3 types of skeletal muscle atrophy ?

Answer 28

1) Clusters of atrophic fibers seen in neurogenic disease. 2) Perifascicular atrophy seen in dermatomyositis (explained in future card). 3) Type II fiber atrophy sparing type I fibers, seen in prolonged corticosteroid therapy or disuse.

Question 29

Inflammatory myopathies include?

Answer 29

Dermatomyositis, Polymyositis, Inclusion body myoscitis

Question 30

_______ is the most common inflammatory myopathy in children.

Answer 30

Dermatomyositis : systemic autoimmune disease presents with proximal muscle weakness, myalgia, and skin changes.

Question 31

Common skin rashes associated with Dermatomyositis (3)?

Answer 31

1) Heliotrope rash - located on the upper eyelids and is often accompanied by eyelid swelling. 2) Butterfly rash: facial rash mildly scaly involves cheeks and bridge of nose. also seen in Lupus patients. 3) Gottron papules: scaling erythematous eruption or dusky red patches on knuckles, elbows, knees

Question 32

Dermatomyositis is associated with what kind of skeletal atropyh?

Answer 32

Perifascicular atrophy: pattern of myofibrer atrophy at the edges of the fascicles

Question 33

Pathogenesis of dermatomyositis

Answer 33

Inappropriate activation of the complement cascade (CC), unknown etiology, leads to the formation of the membrane attack complex (which is just a complex of complement cascade proteins) that relasease inflammatory cytokines and also damages the blood vessels. This cytokines cause the upregulation of certain adhesion molecules called the ICAM and VCAM on the vessel wall. Using these adhension molecules inflammatory cells especially CD4+ T lymphocytes migrate out of the vessel and attack the muscle cells causing injury.

Question 34

______ is an adult onset inflammatory myopathy that shares ______ with dematomyositis but lacks its skin changes.

Answer 34

Polymyositis; proximal muscle weakness/myalgias Polymyositis also has inflammatory involvement of the heart and lungs.

Question 35

Pathogenesis of polymyositis:

Answer 35

CD8 + T-cell autoantibodies attack muscle cells! Polymyositis is a cell-mediated autoimmune disorder in which cytotoxic (CD8-positive) lymphocytes and macrophages invade and destroy myofibers.

Question 36

Unlike dermatomyositis, _________ ________ does not have a major role in polymyositis.

Answer 36

vascular injury, hence the lack of skin rashes

Question 37

Polymyositis is releated to endomysial inflammatory cell infiltrates because?

Answer 37

The inflammatory cells (CD8+ lymphocytes) are in the endomysium (between and around individual myofibers.)

Question 38

________ is the most common inflammatory myopathy in late adulthood, 50-65+y.o.

Answer 38

Inclusion Body Myositis: slowly progressive muscle weakness most severe in quads and distal upper extremities

Question 39

Inclusion Body Myositis can cause ______ do to involvement of esophageal and pharyngeal muscles.

Answer 39

Dysphagia

Question 40

Most myositis-associated autoantibodies are absent in ________.

Answer 40

Inclusion Body Myositis

Question 41

_______ is due to accumulation of misfolded proteins in ____ within the muscle fiber.

Answer 41

Inclusion Body Myositis; vacuoles

Question 42

Examples of toxic myopathies:

Answer 42

- Prescription or recreational drug - Chloroquine and hydroxychloroquine (lysosomal storage myopathy) - ICU myopathy or myosin deficient myopathy (due to corticosteroid therapy) - Thyrotoxic myopathy - Hypothyroidismcan - Alcohol ** slide 24