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Flashcards in MUSCLE Deck (41)

What differential diagnosis should be considered when a young, otherwise healthy person drops dead?

Hypertrophic cardiomyopathy.

[Cardiac myocytes don't work as well as they ought to, so more filaments are added to each cell. # cells does not increase, only the size and number of filaments within each cell]


What is the muscle cell phenotype in hypertrophic cardiomyopathy?

1) hypertrophic cardiac myocytes
2) myocyte disarray
3) interstitial and replacement fibrosis (propensity to arrhythmia)
4) dysplastic intramyocardial arterioles (ischemia)


What type of mutation generally causes hypertrophic cardiomyopathy?

Missense mutation in structural genes.


What are the epidemiological outcomes for persons with HCM?

Most are fine. Some have angina, syncope, dyspnea. BUT, some will drop dead. <1%/year


Clinical Presentations HCM?

– Cardiac murmur (if LV outflow obstruction)
– Cardiac ‘Pump’ Failure (dyspnea, angina)
– Arrhythmia (syncope/sudden death)
– Sports/Family screening



Echocardiogram, EKG, MRI, Family history, genetic testing, chest‐X ray.


What is the inheritance?

Autosomal dominant.


How do muscles increase in size?

Length: recruit myoblasts (add nuclei)
Girth: recruit myoblasts and increase size and number of myofibrils (add sarcomeres)


What are the muscular cows lacking? Talk about that

– Normally made and secreted by muscles as a negative feedback for muscle growth
– May be raised in AIDS patients with muscle wasting


Describe the steps in myostatin processing.

Mature myostatin produced after dimerization and cleavage. Inactive myostatin is bound to follistatin. Binding of dimerized myostatin (now unbound from follistatin) to Activin receptor IIB leads to Smad (tx factor) activation and changes in gene expression.


Malignant hyperthermia is what mode of inheritance? What causes the condition?

Genetic environmental disorder. Must be exposed to anasthetics.

Autosomal dominant. RYR1 mutation (70%).


Which anesthetic agents trigger malignant hyperthermia?



What is the prevalence of malignant hyperthermia?

1/5000 - 1/100,000.

600 deaths/year in US


What is the presentation of malignant hyperthermia?

hypermetabolism, skeletal muscle damage, hyperthermia.

70% mortality if left untreated


Describe the cascade of events leading to malignant hyperthermia?

Stimulus (depolarization) travels down nerve, into muscle cell through t-tubule and through DHP receptors which trigger Ca channel opening (RyR). Ca channel does not close, causing a prolonged contraction. ATPase pumps Ca back into the SR continuously, generating massive amounts of heat.


Specific clinical signs of MH?

Masseter spasm on induction of anesthesia
Increased CO2 production

[non specific: metabolic acidosis, tachycardia, tachypnea, hyperkalemia]


Can diagnose MH with what lab test?

Halothane/caffeine test. Requires a muscle biopsy.


Immediate treatment for MH?

Give DANTROLENE. 2.5 mg/kg

[Bicarbonate; Cool patient (refrigerated saline), gastric lavage, surface cooling, treat arrhythmias, hyperventilate]


Duchenne muscular dystrophy inheritance?

X-linked recessive.

1/3500 males. Mutation in dystrophin gene (DMD).


Clinical signs and symptoms of Duchenne Muscular Dystrophy?

Onset @ 3-5 years. Abnormal gait.

Toe walking, Gower sign, calf pseudohypertrophy

Reproductive fitness 0, wheelchair bound by mid teens at lates.


What is the lab value indicative of DMD?

High creatinine kinase (1000s)

Normal range <200


What is the treatment?


[pulm therapy, walking devices, supportive care, etc.]


What are the levels of muscle unit, from smallest to largest? Which is defined as a "cell"

myofilament (myosin/actin) < myofilament (cell) < muscle fiber < muscle fasiculus (fascicle)


What defines a sarcomere?

Z line --- Z line (from Z to shining Z)


Describe the binding cycle of myosin/actin. Include ATP hydrolysis, power stroke, troponin, tropomysin, Ca, and ADP/Pi in your answer.

Myosin is bound by ATP, unconnected to actin. Tropomysin covers the myosin binding site on the actin molecule. Calcium levels rise, uncovering the myosin binding site. Myosin binds actin and immediately undergoes the power stroke, releasing ADP/Pi as it does so. Myosin remains bound to actin until ATP binds the myosin head, releasing it from actin and allowing the myosin to reset in the "cocked" position. This process continues until the Ca levels in the cell decrease ant the muscle stops firing.

[myosin head is an ATPase]


What muscle type(s) are linked by gap junctions?

Smooth, cardiac


What is the phenomenon described as E-C coupling?

An action potential travels through a motor neuron and into the plasma membrane of a muscle cell. It travels down the t tubule and somehow couples to release Ca from the SR. The t tubule and SR, however, are not cytoplasmically linked.


What receptor in the t-tubule links with the SR to provide the EC coupling? What is it?

The DHPR (dihydropyridine receptor) is a voltage-gated Ca channel


What receptor in the SR membrane links with the t-tubule to provide E-C coupling?

RyR (ryanodine receptor)

[The present theory is that depolarization causes a conformational change in the DHP receptor that in turn causes the calcium release channel to open and Ca flows out of the SR.]


What is a distinguishing feature of cardiac muscle? What functions does it serve?

Intercalated disc.
1. join cells together for contraction
2. gap junctions


Describe the muscle stroke in smooth muscle. What differentiates this from a skeletal muscle contraction?

increased calcium binds calmodulin, calmodulin binds CaM kinase, CaM kinase phosphorylates one of the myosin heads, and the phosphorylated myosin binds actin and force is generated. Ca is pumped out (Ca pump and Na/Ca exchanger). Low calcium inactivates the kinase, myosin is dephosphorylated by a phosphatase.

[smooth muscle cells are small enough that Ca diffusion can do the job without the elaborate SR system. however, this contraction is slow compared to skeletal muscle]

[smooth muscle can remain in a state where myosin is bound to actin continuously without any ATP expenditure. Think...sphincters]

[smooth muscle contains no troponin]


Each ____ is surrounded by sarcoplasmic reticulum.



Each motor neuron innervates ____ muscle and in that muscle it innervates a subset of the total muscle fibers. The muscle fibers innervated by a motor neuron are termed the _____. It is a unit because each time the motor neuron fires an action potential all the muscle fibers innervated by the neuron contract in unison.

one; motor unit


What cells help in muscle repair? Are they inside the muscle cell or outside? What types of muscle have these cells?

Satellite cells spawn myoblasts which help with muscle repair. closely associated, but outside.

Cardiac has none. Skeletal does. Smooth muscles don't either. They de-differentiate, divide and repair themselves.


In which muscle type is extracellular Ca required for contraction?


[smooth contracts w/o. due to coupling of DHPR/RyR in skeletal muscle]


How is tension increased in skeletal muscle?

1) Increased frequency of AP
2) increased motor unit recruitment


How is tension increased in smooth muscle?

1) hormones and neurotransmitters
2) length-tension


What is the effect of exercise?

You ADD myofibrils. Myofibrils can't get bigger in size b/c they are diffusion limited (each wrapped by SR). So the muscle fibers get bigger by adding myofibrils of identical size. Remember, a myofibril is a bundle of myosin and actin with its own Ca storage.


IL-6 is secreted by muscle cells and exercise increases secretion (not LO i think)



LIF (leukemia inhibitory factor) induces proliferation of satellite cells. (not LO i think)



Irisin is released by muscle and increases energy expenditure by changing fat cells into brown-fat-like cells. In mice it reduces diabetes and obesity. (not LO i think)