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Pathophysiology II > Nerves and Skeletal Muscle > Flashcards

Flashcards in Nerves and Skeletal Muscle Deck (73):
1

Fascia

Thick layer of connective tissue covering the entire muscle

2

Epimysium

Connective tissue wrapping the entire muscle

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Perimysium

Fibrous tissue that covers each fascicle

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Endomysium

Tissue that covers the muscle fiber

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Sarcolemma

Cell membrane that covers the muscle fiber

6

Excitation- contraction coupling

When an electrical stimulus triggers the release of Ca2+ from the sarcoplasmic reticulum, which causes muscle contraction

7

How do patients with a disorder of the neuromuscular junction present?

Painless weakness

8

2 antibody mediated diseases of the neuromuscular junction

Myasthenia Gravis and Lambert-Eaten Myasthenic Syndrome (LEM Syndrome)

9

What is the pathogenesis of Myasthenia Gravis?

Autoantibodies directed at post-synaptic Ach receptors, which causes aggregation and degradation of the receptors

10

What is the age and female/male ratio of Myasthenia Gravis?

Bi-modal distribution
In young adults = female: male is 2:1
In older adults = male > female

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Clinical features of myasthenia gravis

-Related to a thymus disorder which leads to the creation of abnormal antibodies
-weakness that worsens with exertion and gets worse as the day goes on
-diplopia and ptosis (eyelid drooping)
-starts with eyes and moves downwards

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Pathogenesis of LEM Syndrome

Autoantibodies inhibit pre-synaptic Ca channel so Ach cannot be released. With no Ach, there is no contraction

13

Clinical features of LEM syndrome

-Related to malignancy, specifically small cell carcinoma in smokers
-rapid repetitive stimulation increases muscle response
-starts at the bottom extremities and works upwards

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Satellite cell

Muscle specific stem cell

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Pathway of satellite cell

Satellite cell —> myoblast —> myotube —>myofiber —> mature fiber bundle

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Type 1 muscle fiber

-slow twitch “slow and steady”
-high fatigue resistance
-low force
-high mitochondria
-high aerobic enzymes

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Type II muscle fiber

-fast twitch
-high force
-easily fatigues
-low mitochondria
-low aerobic enzymes

18

Clusters/groups of muscle atrophy indicate what?

Nerve injury

19

Perifascicular atrophy indicates what?

Dermatomyositis

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Type II atrophy without type I indicates what?

Prolonged corticosteroid use, usually in the ICU

21

A skeletal muscle disorder can either be:

Myopathic injury or neurogenic injury

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3 Types of inflammatory myopathies

1. Dermatomyositis
2. Inclusion body myositis
3. Polymyositis

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Pathogenesis of dermatomyositis

Main mediator = CD4+
-Autoantibodies attack endothelial capillaries
-the complement system is activated which creates a MAC complex
-the damage causes necrosis of tissue and release of cytokines
-loss of endothelial cells leads to ischemia and VCAM and ICAM are unregulated on cells which ends to aggregated T and B cells

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Clinical features of dermatomyositis

-proximal muscle weakness (thigh, arm)
-heliotrope rash = purple rash on face
-gottron papules = red papules on joints
-elevated serum creatine

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Dermatomyositis is most common in:

Children

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Dermatomyositis mainly affects:

Skin and muscle

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Polymyositis is a:

Diagnosis of exclusion

28

Polymyositis usually affects:

Adults

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Main mediator in polymyositis:

CD8 T cells

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Clinical features of polymyositis

-myalgia
-proximal muscle weakness
-can include heart and lungs, causing CHF
-lacks skin component
-no vascular injury/capillary features

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Inclusion body

Abnormal protein aggregate

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Inclusion body myositis usually affects:

Older adults 65 yrs and up

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Inclusion body myositis is the only one that does NOT include:

Autoantibodies

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Clinical features of inclusion body myositis

-weakness of distal muscles
-elevated serum creatine levels
-progresses slowly

35

Examples of toxic myopathies

-prescription drugs
-hyperthyroidism
-hypothyroidism
-hydroxychlroquine
-ICU myopathy (steroid use)
-alcohol

36

Muscular dystrophy can either be due to:

1. Defects in the ECM
2. Receptor defects in ECM

37

Duchenne + Becker muscular dystrophy pathogenesis

-X linked mutation in dystrophin. In duchenne, there is one frame shift mutation which leads to no dystrophin at all. In Becker, there is a truncated protein but a portion of dystrophin is created.
- muscle damage out weighs repair
-muscle is replaced with fat

38

Clinical features of Duchenne/Becker muscular dystrophy

-normal at birth
-development of walking is delayed
-child displays tripod/Gower sign
-pseudo hypertrophy
-death d/t heart and lung issues
-life span is greatly reduced

39

Main characteristic of limb-girdle muscular dystrophy

Proximal muscle weakeness

40

Pathogenesis of myotonic dystrophy

CTG repeats in the DMPK gene, which is important for splicing. With mis-spliced DMPK gene, chloride channels are mutated (CLC1) which are necessary for muscle relaxation

41

Clinical features of myotonic dystrophy

*myotonia - muscles cannot relax
-skeletal muscle weakness
-cataracts
-endocrine disorders
-cardiomyopathies

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3 main types of muscular dystrophy caused by defects in ECM receptors

1. Limb-girdle
2. Duchenne/Becker
3. Myotonic

43

Pathogenesis of spinal muscular atrophy

-mutation in the SMN1 gene which is responsible for the survival of motor neurons. Severity depends on the amount of SMN2 genes a person has

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Spinal muscular atrophy

Loss of motor neurons that leads to atrophy of voluntary muscles

45

Clinical features of spinal muscular atrophy

-hypotonia causes floppy baby syndrome
-usually affects muscles closest to the center of the body
-complications d/t muscles used for breathing and swallowing

46

3 diseases of lipid/glycogen metabolism

1. Carnitine palmitoyltransferase II deficiency
2. Myophospheryase deficiency
3. Acid Maltase deficiency

47

Pathogenesis of carnitine palmitoyltransferase II deficiency

There is impairment of the carnitine shuttle, which is necessary to transport long chain fatty acid from the cytoplasm to the mitochondria to turn FFA to energy. With impairment of the shuttle, the body cannot use FFA for energy

48

Clinical features of carnitine palmitotransferase II deficiency

-Episodic during exercise/fasting
-cramping, pain, rhabdomyolysis

49

Diseases of lipid/glycogen metabolism can either be:

-during exercise/fasting - periodic
-slowly progressive

50

Pathogenesis myophosphorylase deficiency

Myophosphorylase is used to turn glycogen into glucose. With a deficiency of this the body cannot turn glycogen into glucose for energy. This is slightly compensated because there is also myophosphorylase stored in the liver

51

Clinical features of myophosphorylase deficiency

Episodic/ periodic during exercise and fasting

52

Pathogenesis of acid maltase deficiency

Acid maltase is a lysosomal enzyme responsible for converting glycogen into glucose. With a deficiency, glycogen accumulates in the lysosomes and causes dysfunction in normal cells.

53

Two types of acid maltase deficiency

1. Pompe disease - severe. If no enzyme replacement is used, baby usually doesn’t live past 8 months and develops CHF
2. Adult onset myopathy - less severe

54

Pathogenesis of mitochondrial myopathies

-Maternal inheritance
-any damage to mitochondria = less ATP for the cells
-abnormal aggregates of mitochondria. Looks like “ragged red fibers”

55

Clinical features of mitochondrial myopathies

-weakness
-elevated CK
-rhabdomyolysis
-chronic progressive external ophthalmoplegia. Affects the eyes first because they require a lot of ATP

56

Clinical features of ion channel myopathy

-epilepsy
-migraine
-movement disorders
-nerve disease
-muscle disease
* depends on what organ is affected, and ion pumps are important in all organs

57

Ion channel mutation can either cause:

Increased excitability (hypertonia) or decreased excitability (hypotonia)

58

Hypotonia can be caused by: (3 times)

-hyperkalemia
-hypokalemia
-normokalemia

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Hyperkalemia in ion channel myopathy

-mutation is in the sodium channel
-increased potassium d/t stress, food
-sodium channel cannot be inactivated so at first there is myotonia and then there is fatigue and paralysis for hours/days

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Example of hyperkalemia ion channel myopathy

SCN4A

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Hyperkalemia, hypokalemia, and normokalemia cause what type of paralysis?

Periodic paralysis

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Hypokalemia in ion channel myopathy

-mutation is in the calcium channel
-while taking in glucose or sodium containing food
-calcium cannot leave the sarcoplasmic reticulum so there is no muscle contraction

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Example of hypokalemia in ion channel myopathy

CACNA1S

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KCNJ2

-another example of hypokalemia
-mutation is with the potassium channel
-causes Anderson twail syndrome

65

Anderson twail Syndrome

-caused by potassium ion pump dysfunction
-periodic paralysis
-skeletal muscle abnormalities
-arrhythmias

66

CLC1 dysfunction

-issue is with the chloride channel
-causes myotonia congenita and myotonic dystrophy

67

RYR1 dysfunction

-too much ATP is lost which causes malignant hyperthermia

68

Main parts of a neuron

-axon
-dendrites
-terminal boutons
-myelin sheath

69

Pathogenesis of Guillain-Barre Syndrome “GBS”

-immune mediated destruction of myelin sheath
-T cell mediated
-nerve conduction is slowed

70

Clinical features Guillain-Barre Syndrome

-ascending paralysis that begins in the lower limbs
-loss of pain sensation
-elevated CSF proteins due to increased permeability from inflammation
-death d/t respiratory paralysis

71

What is the most common cause of metabolic neuropathy?

Diabetes

72

Pathogenesis of diabetic neuropathy

-hyperglycemia causes modification of proteins, which leads to dysfunction of proteins
-hyperglycemia also causes activation of inflammatory signaling, which causes damage to neurons and ultimately neuropathy
-hyperglycemia causes glucose to take an alternate pathway and become sorbitol by using NADPH. Using NADPH prevents it from being used as an antioxidant, so there is increase ROS damage to nerves

73

Clinical features of diabetic neuropathy

-numbness and tingling
-stocking and glove phenomenon
-increased chance for skin ulcers
-can cause autonomic neuropathy (sexual dysfunction, bladder emptying, postural hypotension