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STEP 1 > High Yield Topics-MSK > Flashcards

High Yield Topics-MSK Flashcards

1
Q

Describe MOA of Neuromuscular contraction

A
  1. Action potential reaches down the axon, opening the voltage-gated Ca+2 channels
  2. Ach gets released into NMJ and binds to POSTSYNAPTIC Ach receptors (nicotinic receptors)
  3. Muscle cell gets depolarized, and depolarization spreads the entire muscle cell via the T-tubules
  4. Depolarization reaches and opens Ca+ channels (dihydropyridine receptors) which is mechanically coupled to ryanodine receptor (RR)
  5. Ca+2 gets released from SR into the cytoplasm
  6. Ca+2 binds to troponin –> shifting tropomyosin that’s blocking the myosin-binding site on actin filament
  7. The myosin head that’s attached to ADP + Pi binds to the myosin-binding site –> forms the bridge.
  8. The myosin head releases Pi, initiating the power stroke –> contraction (pulling actin filament toward myosin, shortening of muscle occurs)
  9. ADP from the myosin gets released at the end of power stroke
  10. ATP attaches to the myosin –> myosin head detaches from actin. Ca+2 gets re-sequestered.
  11. ATP hydrolyzes into ADP + pi –> the myosin head returns to its cocked (high energy) position
  12. Remaining Ca+2 allows the myosin head to form a new cross-bridge
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2
Q

What remains the same length during muscle contraction/shortening (power stroke)?

A

A band

*STUDY AID: “A” band is “A”lways the same length

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3
Q

What shortens during muscle contraction/shortening (power stroke)?

A

HIZ

  • H band
  • I band
  • Z line to Z line
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4
Q

What disorder is caused by autoantibodies against postsynaptic Ach receptors (nicotinic receptors)?

A

Myasthenia gravis (NMJ disease)

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5
Q

What disorder is caused by autoantibodies against presynaptic Ca+2 channels

A

Lambert-Eaton Myasthenic syndrome (NMJ disease)

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6
Q

What disorder is characterized by proximal muscle weakness that WORSENS with muscle use?

A

Myasthenia gravis (NMJ disease)

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7
Q

What disorder is characterized by proximal muscle weakness that IMPROVES with muscle use?

A

Lambert-Eaton Myasthenic syndrome (NMJ disease)

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8
Q

What NMJ disorder presents with spared reflexes?

A

Myasthenia gravis (NMJ disease)

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9
Q

What NMJ disorder presents with decreased DTR (deep-tendon reflex)?

A

Lambert-Eaton Myasthenic syndrome (NMJ disease)

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10
Q

What NMJ disorder presents with autonomic symptoms (dry mouth, constipation, impotence)

A

Lambert-Eaton Myasthenic syndrome (NMJ disease)

  • decreased Ach release decreases parasympathetic response in other organs –> dry mouth, constipation, impotence
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11
Q

What NMJ disorder presents with dyspnea, dysphagia, difficulty chewing, ptosis, and diplopia?

A

Myasthenia gravis (NMJ disease)

  • other muscles (respiratory, bulbar/neck, eyes) are affected as well in MG
  • STUDY AID: these muscles have nicotinic receptors since they can be voluntarily moved (breathing, swallowing, chewing, blinking)
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12
Q

Myasthenia gravis is associated with what malignancy?

A

Thymoma, thymic hyperplasia

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13
Q

Lambert-Eaton Myasthenic syndrome is associated with what malignancy?

A

SCLC

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14
Q

What NMJ disorder can be treated with AchE inhibitors?

A

Myasthenia gravis

  • Lambert-Eaton Myasthenic syndrome won’t benefit!
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15
Q

Which AChE inhibitors can be used to tx Myasthenia gravis?

A

neostigmine and pyridostigmine

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16
Q

What condition presents with increased neuromuscular activity (hyperreflexia, tremor, seizure), increased autonomic instability (hyperthermia, diaphoresis, diarrhea), and altered mental status; caused by drug that increases 5-HT levels (serotonin)?

A

Serotonin Syndrome

  • STUDY AID: 3 A’s
  • increased Activity (neuromuscular)
  • increased Autonomic instability
  • Altered mental status
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17
Q

What condition presents with a very high BP due to eating tyramine-rich foods with MAOIs

A

Hypertensive crisis

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18
Q

What foods are rich in tyramine?

A

cheese, wine, cured meats, chocolate

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19
Q

What is the MOA of tyramine that causes hypertensive crisis?

A

tyramine displaces other neurotransmitters such as NE in the synaptic cleft, leading to increased sympathetic stimulation

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20
Q

What condition is a reaction to antipsychotics (ex. dopamine antagonists) and presents with fever, muscle rigidity (lead-pipe), increased CK (sign of rhabdomyolysis) enzymes, and encephalopathy?

A

Neuroleptic malignant syndrome

  • Be able to distinguish this from serotonin syndrome!
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21
Q

Tx for serotonin syndrome

A

Cyproheptadine (5-HT receptor antagonist)

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22
Q

Tx for Hypertensive crisis

A

Phentolamine (reversible a1 & a2 antagonist)

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23
Q

Tx for Neuroleptic malignant syndrome

A

Dantrolene, dopamine agonist (bromocriptine)

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24
Q

What condition is a reaction to INHALED anesthetics or succinylcholine and presents with hyperthermia and severe muscle contractions?

A

Malignant Hyperthermia

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25
Q

What drug is used to tx malignant hyperthermia and MOA?

A

Dantrolene: Ryanodine receptor antagonist –> inhibits release of Ca+2 from SR –> decrease muscle contraction

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26
Q

What condition is caused by a mechanical wear and tear that destroys articular CARTILAGE?

A

Osteoarthritis

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27
Q

What type of cell is responsible for degradation without adequate repair, leading to Osteoarthritis?

A

Chondrocytes

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28
Q

What type of arthritis presents with pain that worsens throughout the day but better with rest?

A

Osteoarthritis

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29
Q

Age, female, obesity, and joint trauma increase the risk of what type of arthritis?

A

Osteoarthritis

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30
Q

What type of arthritis presents with asymmetric joint pain and loss of cartilage that begins medially?

A

Osteoarthritis

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31
Q

What type of arthritis presents with bony spurs/growths called nodes at DIP (Heberden nodes) and PIP (Bouchard nodes) joints?

  • STUDY AID: B comes before H in alphabet –> B for proximal and H for distal
A

Osteoarthritis

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32
Q

Osteoarthritis involves 1st CMC (joint b/w thumb and wrist) but does NOT involve

A

MCP (metacarpalphalangeal joint)

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33
Q

Osteoarthritis will have (high/low) WBC count in synovial fluid

A

low

*Osteoarthritis is not an autoimmune disease!

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34
Q

What condition is caused by an autoimmune response directed against autoantigens in the joints –> inflammatory joint destruction and BONE?

A

Rheumatoid arthritis

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35
Q

Antibodies associated with Rheumatoid arthritis are

A
  1. rheumatoid factor (IgM antibody against Fc region of IgG)

2. anti-citrullinated protein antibodies

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36
Q

What type of arthritis presents with symmetric joint pain and other systemic symptoms such as fever, fatigue, and weight loss?

A

Rheumatoid arthritis

  • NO systemic symptoms for osteoarthritis!
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37
Q

What type of arthritis presents with morning stiffness/pain (when not used) that improves with use?

A

Rheumatoid arthritis

38
Q

Rheumatoid arthritis involves joint space that’s replaced by

A

Pannus (a mass of fibroblast-like cells making granulation tissue)

39
Q

Rheumatoid arthritis will have a synovial fluid full of

A

inflammatory wbc infiltrates and later is replaced by Pannus

40
Q

What type of arthritis presents with finger joint deformities –> swan neck, boutonniere and ulnar deviation

A

Rheumatoid arthritis

41
Q

Rheumatoid arthritis involves PIP, wrist, and MCP (metacarpalphalangeal joint), but does NOT involve

A

DIP or 1st CMC (joint b/w thumb and wrist)

42
Q

Tx for Osteoarthritis

A
  • Decrease activity that causes wear/tear
  • pain relief (acetaminophen, NSAIDs)
  • steroid injections
43
Q

Tx for Rheumatoid arthritis

A

First line acute tx:

  • NSAIDs
  • steroid injections

Long-term tx: Disease Modifying Agents

  • Methotrexate, sulfasalazine
  • biologics (TNF-a inhibitors)
44
Q

Which type of arthritis involves extraarticular manifestation (lung disease, amyloidosis, sjogren’s)

A

Rheumatoid arthritis

45
Q

Connective tissue within muscle changes to bone during healing after a trauma; example of mesenchymal metaplasia

A

Myositis ossificans

46
Q

Intercostal nerves, arteries, and veins are located along the (superior/inferior) margin of their respective rib

A

inferior

47
Q

Lupus is associated with what antibodies (3)?

A
  1. ANA (antinuclear antibody)
  2. anti-dsDNA
  3. anti-smith (antibodies to snRNPs)
  • anti-dsDNA & anti-smith have higher specificity!
48
Q

Antibody (besides anti-dsDNA, anti-smith, and ANA) highly associated with SLE, which can cause paradoxical aPTT prolongation that is not corrected by the addition of normal platelet-containing plasma; usually has a history of thrombosis or pregnancy loss

A

Antiphospholipid antibodies

49
Q

Three types of Antiphospholipid antibodies

A
  1. Lupus anticoagulant
  2. Anticardiolipin
  3. Anti-B2 glycoprotein I
50
Q

Which antiphospholipid antibody can cause false + VDRL/RPR (syphilis test)?

A

Anticardiolipin

51
Q

Tx for Antiphospholipid syndrome

A

anticoagulant

52
Q

The most common type of glomerulonephritis seen in lupus patients; caused by immune complex deposition in glomeruli) that leads to thickening of glomerular capillary walls with “wire-loop” structures on Light Microscope

A

Diffuse Proliferative Glomerulonephritis (DPGN)

53
Q

A cardiovascular manifestation of lupus (small, sterile vegetations on BOTH SIDES of the mitral or aortic valve)

A

Libman-Sacks Endocarditis

54
Q

A cardiovascular manifestation of lupus (accelerated atherosclerosis)

A

Coronary Artery Disease

55
Q

Drug-Induced SLE is associated with drugs that are metabolized by _______ in the liver; genetically SLOW acetylators are at greater risk for drug-induced lupus

A

acetylation (conjugation)

56
Q

Antibody associated with Drug-Induced SLE

A

Anti-histone antibody

57
Q

What two drugs have the highest risk of causing Drug-Induced SLE?

A

Procainamide and Hydralazine

58
Q

An autoimmune disorder characterized by lymphocytic inflammation in “exocrine” glands (salivary, lacrimal); presents with joint pain, dry eyes (keratoconjunctivitis sicca), dry mouth (xerostomia), and parotid enlargement

A

Sjogren syndrome

59
Q

Two antibodies associated with Sjogren syndrome

A
  1. Anti-Ro (SS-A)

2. Anti-La (SS-B)

60
Q

An autoimmune disease common in women that is caused by proliferation of connective tissue, which leads to diffuse thickening and hardening of the skin and inner organs; 2 major types (diffuse vs. limited)

A

Scleroderma

aka. systemic sclerosis

61
Q

(Diffuse/Limited) scleroderma is characterized by limited skin findings to fingers and face; other manifestations include calcinosis (calcified collagen deposition on fingers), anti-centromere antibody, Raynaud phenomenon, esophageal dysmotility, and sclerodactyly (hand curling due to skin hardening), and telangiectasia

A

Limited Scleroderma

aka. CREST Syndrome

  • STUDY AID: CREST
  • Calcinosis/anti-Centromere antibody
  • Raynaud phenomenon
  • Esophageal dysmotility
  • Sclerodactyly
  • Telangiectasia
62
Q

(Diffuse/Limited) scleroderma is characterized by widespread skin involvement, rapid progression of visceral involvement

A

Diffuse Scleroderma

63
Q

Antibodies associated with diffuse scleroderma vs. limited/CREST scleroderma

A

Diffuse:

  • Anti-Scl-70 antibody (anti-DNA topoisomerase I antibody)
  • Anti-RNA polymerase III antibody

Limited:
- anti-centromere antibody

64
Q

An autoimmune disorder that is due to over-expression of MHC I proteins on sarcolemma leading to infiltration with CD8+ T lymphocytes and myocyte damage; presents with SYMMETRIC PROXIMAL muscle weakness

A

Polymyositis

65
Q

An autoimmune disorder that presents similar to polymyositis (SYMMETRIC PROXIMAL muscle weakness), but also involves dermal manifestations (Gottron papules and “shawl and face” rash)

A

Dermatomyositis

66
Q

Red or violet-colored bumps that occur on the top part of the hand, specifically the knuckles; presents in Dermatomyositis

A

Gottron Papules

67
Q

A non-specific antibody associated with polymyositis/dermatomyositis

A

ANA (antinuclear antibody)

68
Q

Three specific antibodies associated with polymyositis/dermatomyositis

A
  1. anti-Jo-1 (histidyl-tRNA synthetase)
  2. anti-Mi-2 (helicase)
  3. anti-SRP (signal recognition particle)
    * STUDY AID: “DermatoMileyCyrus is ANTI-JOnas brothers”
69
Q

What will be increased in serum finding for both polymyositis and dermatomyositis?

A

↑ CK

70
Q

(Polymyositis/dermatomyositis/both) can indicate underlying malignancy.

A

BOTH

71
Q

(Polymyositis/dermatomyositis) histology will show patchy ENDOMYSIAL (individual muscle fiber) inflammatory infiltrate

A

Polymyositis

72
Q

(Polymyositis/dermatomyositis) histology will show patchy PERIMYSIAL (around blood vessels besides muscle fiber) inflammatory infiltrate

A

Dermatomyositis

73
Q

Bone metastasis (secondary tumor from primary malignancy of other organ) that is due to new bone formation by osteoblasts > outweighing osteolytic processes; increase in radiographic density

A

Osteoblastic metastasis

aka. Osteoblastic lesion

74
Q

Bone metastasis (secondary tumor from primary malignancy of other organ) that is due to osteolytic processes outweighing new bone formation; decrease in radiographic density

A

Osteolytic metastasis

aka. Osteolytic lesion

75
Q

Multiple myeloma, thyroid cancer, kidney cancer, melanoma, and non-SCLC are primary malignancies that can cause (osteoblastic/osteolytic) metastasis

A

Osteolytic metastasis

76
Q

Prostate cancer and SCLC are primary malignancies that can cause (osteoblastic/osteolytic) metastasis

A

Osteoblastic metastasis

77
Q

In primary osteoporosis (not caused by a medical disorder or trauma), serum calcium, phosphorus, and parathyroid hormone levels are

A

NORMAL

78
Q

Bone loss predominantly affects ______ bone in EARLY phase of Osteoporosis, but over time, cortical bone becomes involved

A

trabecular

79
Q

Chronic, systemic use of _______ promotes osteoporosis and increases the risk of fractures

A

glucocorticoids

80
Q

Long-term acid suppression with _____ is associated with an increased risk of osteoporotic fractures, possibly due to decreased calcium absorption

A

Proton Pump Inhibitors (PPI)

*Calcium carbonate needs stomach acid to be absorbed

81
Q

Long-term use of GnRH agonists (Leuprolide) suppresses pituitary LH release and leads to the ↓ production of ______ and can lead to accelerated bone loss and ↑ risk for osteoporosis

  • Constant GnRH stimulation suppresses gonadotropins, whereas pulsatile GnRH stimulation induces gonadotropins
A

Testosterone

82
Q

Thiazide diuretics increase calcium absorption in the _______ within the nephron and are associated with increased bone mineral density; recommended for treatment of HTN in patients at risk for osteoporosis

A

distal convoluted tubules (DCT)

83
Q

What class of drugs exhibit estrogen antagonist and agonist properties in a tissue-specific manner?

A

Selective estrogen receptor modulators (SERMs)

84
Q

What SERM has estrogen AGONIST activity on bone, which decreases bone resorption and improves bone density?

A

Raloxifene

85
Q

What SERM has estrogen ANTAGONISTIC effect on breast tissue and can decrease the risk of breast cancer?

A

Raloxifene

86
Q

What SERM has estrogen ANTAGONISTIC effect on uterus and does not increase the risk of endometrial cancer?

A

Raloxifene

87
Q

The NFκB (RANK) and RANK-L (ligand) interaction is essential for the formation and differentiation of

A

Osteoclasts

88
Q

What regulatory factor blocks the binding of RANK-L to RANK and ↓ formation of mature osteoclasts, leading to ↓ bone resorption?

A

Osteoprotegerin (OPG)

89
Q

Low estrogen level causes osteoporosis by decreasing ________ production, increasing RANKL-RANK binding in osteoclast precursors

A

Osteoprotegerin (OPG)

90
Q

A monoclonal antibody used in the Tx of postmenopausal osteoporosis that binds to RANKL to inhibit its binding to RANK receptor on osteoclasts

A

Denosumab

91
Q

What drug has a chemical structure similar to that of pyrophosphate and attach to hydroxyapatite binding sites on bony surfaces to inhibit bone resorption by osteoclasts?

A

Bisphosphonates

92
Q

The most common side effect of Bisphosphonate that can be avoided by swallowing the medication with enough water + maintaining upright position for 30 minutes

A

Esophagitis

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