High Yield Topics-MSK Flashcards
Describe MOA of Neuromuscular contraction
- Action potential reaches down the axon, opening the voltage-gated Ca+2 channels
- Ach gets released into NMJ and binds to POSTSYNAPTIC Ach receptors (nicotinic receptors)
- Muscle cell gets depolarized, and depolarization spreads the entire muscle cell via the T-tubules
- Depolarization reaches and opens Ca+ channels (dihydropyridine receptors) which is mechanically coupled to ryanodine receptor (RR)
- Ca+2 gets released from SR into the cytoplasm
- Ca+2 binds to troponin –> shifting tropomyosin that’s blocking the myosin-binding site on actin filament
- The myosin head that’s attached to ADP + Pi binds to the myosin-binding site –> forms the bridge.
- The myosin head releases Pi, initiating the power stroke –> contraction (pulling actin filament toward myosin, shortening of muscle occurs)
- ADP from the myosin gets released at the end of power stroke
- ATP attaches to the myosin –> myosin head detaches from actin. Ca+2 gets re-sequestered.
- ATP hydrolyzes into ADP + pi –> the myosin head returns to its cocked (high energy) position
- Remaining Ca+2 allows the myosin head to form a new cross-bridge
What remains the same length during muscle contraction/shortening (power stroke)?
A band
*STUDY AID: “A” band is “A”lways the same length
What shortens during muscle contraction/shortening (power stroke)?
HIZ
- H band
- I band
- Z line to Z line
What disorder is caused by autoantibodies against postsynaptic Ach receptors (nicotinic receptors)?
Myasthenia gravis (NMJ disease)
What disorder is caused by autoantibodies against presynaptic Ca+2 channels
Lambert-Eaton Myasthenic syndrome (NMJ disease)
What disorder is characterized by proximal muscle weakness that WORSENS with muscle use?
Myasthenia gravis (NMJ disease)
What disorder is characterized by proximal muscle weakness that IMPROVES with muscle use?
Lambert-Eaton Myasthenic syndrome (NMJ disease)
What NMJ disorder presents with spared reflexes?
Myasthenia gravis (NMJ disease)
What NMJ disorder presents with decreased DTR (deep-tendon reflex)?
Lambert-Eaton Myasthenic syndrome (NMJ disease)
What NMJ disorder presents with autonomic symptoms (dry mouth, constipation, impotence)
Lambert-Eaton Myasthenic syndrome (NMJ disease)
- decreased Ach release decreases parasympathetic response in other organs –> dry mouth, constipation, impotence
What NMJ disorder presents with dyspnea, dysphagia, difficulty chewing, ptosis, and diplopia?
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)
Myasthenia gravis is associated with what malignancy?
Thymoma, thymic hyperplasia
Lambert-Eaton Myasthenic syndrome is associated with what malignancy?
SCLC
What NMJ disorder can be treated with AchE inhibitors?
Myasthenia gravis
- Lambert-Eaton Myasthenic syndrome won’t benefit!
Which AChE inhibitors can be used to tx Myasthenia gravis?
neostigmine and pyridostigmine
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)?
Serotonin Syndrome
- STUDY AID: 3 A’s
- increased Activity (neuromuscular)
- increased Autonomic instability
- Altered mental status
What condition presents with a very high BP due to eating tyramine-rich foods with MAOIs
Hypertensive crisis
What foods are rich in tyramine?
cheese, wine, cured meats, chocolate
What is the MOA of tyramine that causes hypertensive crisis?
tyramine displaces other neurotransmitters such as NE in the synaptic cleft, leading to increased sympathetic stimulation
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?
Neuroleptic malignant syndrome
- Be able to distinguish this from serotonin syndrome!
Tx for serotonin syndrome
Cyproheptadine (5-HT receptor antagonist)
Tx for Hypertensive crisis
Phentolamine (reversible a1 & a2 antagonist)
Tx for Neuroleptic malignant syndrome
Dantrolene, dopamine agonist (bromocriptine)
What condition is a reaction to INHALED anesthetics or succinylcholine and presents with hyperthermia and severe muscle contractions?
Malignant Hyperthermia
What drug is used to tx malignant hyperthermia and MOA?
Dantrolene: Ryanodine receptor antagonist –> inhibits release of Ca+2 from SR –> decrease muscle contraction
What condition is caused by a mechanical wear and tear that destroys articular CARTILAGE?
Osteoarthritis
What type of cell is responsible for degradation without adequate repair, leading to Osteoarthritis?
Chondrocytes
What type of arthritis presents with pain that worsens throughout the day but better with rest?
Osteoarthritis
Age, female, obesity, and joint trauma increase the risk of what type of arthritis?
Osteoarthritis
What type of arthritis presents with asymmetric joint pain and loss of cartilage that begins medially?
Osteoarthritis
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
Osteoarthritis
Osteoarthritis involves 1st CMC (joint b/w thumb and wrist) but does NOT involve
MCP (metacarpalphalangeal joint)
Osteoarthritis will have (high/low) WBC count in synovial fluid
low
*Osteoarthritis is not an autoimmune disease!
What condition is caused by an autoimmune response directed against autoantigens in the joints –> inflammatory joint destruction and BONE?
Rheumatoid arthritis
Antibodies associated with Rheumatoid arthritis are
- rheumatoid factor (IgM antibody against Fc region of IgG)
2. anti-citrullinated protein antibodies
What type of arthritis presents with symmetric joint pain and other systemic symptoms such as fever, fatigue, and weight loss?
Rheumatoid arthritis
- NO systemic symptoms for osteoarthritis!
What type of arthritis presents with morning stiffness/pain (when not used) that improves with use?
Rheumatoid arthritis
Rheumatoid arthritis involves joint space that’s replaced by
Pannus (a mass of fibroblast-like cells making granulation tissue)
Rheumatoid arthritis will have a synovial fluid full of
inflammatory wbc infiltrates and later is replaced by Pannus
What type of arthritis presents with finger joint deformities –> swan neck, boutonniere and ulnar deviation
Rheumatoid arthritis
Rheumatoid arthritis involves PIP, wrist, and MCP (metacarpalphalangeal joint), but does NOT involve
DIP or 1st CMC (joint b/w thumb and wrist)
Tx for Osteoarthritis
- Decrease activity that causes wear/tear
- pain relief (acetaminophen, NSAIDs)
- steroid injections
Tx for Rheumatoid arthritis
First line acute tx:
- NSAIDs
- steroid injections
Long-term tx: Disease Modifying Agents
- Methotrexate, sulfasalazine
- biologics (TNF-a inhibitors)
Which type of arthritis involves extraarticular manifestation (lung disease, amyloidosis, sjogren’s)
Rheumatoid arthritis
Connective tissue within muscle changes to bone during healing after a trauma; example of mesenchymal metaplasia
Myositis ossificans
Intercostal nerves, arteries, and veins are located along the (superior/inferior) margin of their respective rib
inferior
Lupus is associated with what antibodies (3)?
- ANA (antinuclear antibody)
- anti-dsDNA
- anti-smith (antibodies to snRNPs)
- anti-dsDNA & anti-smith have higher specificity!
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
Antiphospholipid antibodies
Three types of Antiphospholipid antibodies
- Lupus anticoagulant
- Anticardiolipin
- Anti-B2 glycoprotein I
Which antiphospholipid antibody can cause false + VDRL/RPR (syphilis test)?
Anticardiolipin
Tx for Antiphospholipid syndrome
anticoagulant
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
Diffuse Proliferative Glomerulonephritis (DPGN)
A cardiovascular manifestation of lupus (small, sterile vegetations on BOTH SIDES of the mitral or aortic valve)
Libman-Sacks Endocarditis
A cardiovascular manifestation of lupus (accelerated atherosclerosis)
Coronary Artery Disease
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
acetylation (conjugation)
Antibody associated with Drug-Induced SLE
Anti-histone antibody
What two drugs have the highest risk of causing Drug-Induced SLE?
Procainamide and Hydralazine
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
Sjogren syndrome
Two antibodies associated with Sjogren syndrome
- Anti-Ro (SS-A)
2. Anti-La (SS-B)
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)
Scleroderma
aka. systemic sclerosis
(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
Limited Scleroderma
aka. CREST Syndrome
- STUDY AID: CREST
- Calcinosis/anti-Centromere antibody
- Raynaud phenomenon
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasia
(Diffuse/Limited) scleroderma is characterized by widespread skin involvement, rapid progression of visceral involvement
Diffuse Scleroderma
Antibodies associated with diffuse scleroderma vs. limited/CREST scleroderma
Diffuse:
- Anti-Scl-70 antibody (anti-DNA topoisomerase I antibody)
- Anti-RNA polymerase III antibody
Limited:
- anti-centromere antibody
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
Polymyositis
An autoimmune disorder that presents similar to polymyositis (SYMMETRIC PROXIMAL muscle weakness), but also involves dermal manifestations (Gottron papules and “shawl and face” rash)
Dermatomyositis
Red or violet-colored bumps that occur on the top part of the hand, specifically the knuckles; presents in Dermatomyositis
Gottron Papules
A non-specific antibody associated with polymyositis/dermatomyositis
ANA (antinuclear antibody)
Three specific antibodies associated with polymyositis/dermatomyositis
- anti-Jo-1 (histidyl-tRNA synthetase)
- anti-Mi-2 (helicase)
- anti-SRP (signal recognition particle)
* STUDY AID: “DermatoMileyCyrus is ANTI-JOnas brothers”
What will be increased in serum finding for both polymyositis and dermatomyositis?
↑ CK
(Polymyositis/dermatomyositis/both) can indicate underlying malignancy.
BOTH
(Polymyositis/dermatomyositis) histology will show patchy ENDOMYSIAL (individual muscle fiber) inflammatory infiltrate
Polymyositis
(Polymyositis/dermatomyositis) histology will show patchy PERIMYSIAL (around blood vessels besides muscle fiber) inflammatory infiltrate
Dermatomyositis
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
Osteoblastic metastasis
aka. Osteoblastic lesion
Bone metastasis (secondary tumor from primary malignancy of other organ) that is due to osteolytic processes outweighing new bone formation; decrease in radiographic density
Osteolytic metastasis
aka. Osteolytic lesion
Multiple myeloma, thyroid cancer, kidney cancer, melanoma, and non-SCLC are primary malignancies that can cause (osteoblastic/osteolytic) metastasis
Osteolytic metastasis
Prostate cancer and SCLC are primary malignancies that can cause (osteoblastic/osteolytic) metastasis
Osteoblastic metastasis
In primary osteoporosis (not caused by a medical disorder or trauma), serum calcium, phosphorus, and parathyroid hormone levels are
NORMAL
Bone loss predominantly affects ______ bone in EARLY phase of Osteoporosis, but over time, cortical bone becomes involved
trabecular
Chronic, systemic use of _______ promotes osteoporosis and increases the risk of fractures
glucocorticoids
Long-term acid suppression with _____ is associated with an increased risk of osteoporotic fractures, possibly due to decreased calcium absorption
Proton Pump Inhibitors (PPI)
*Calcium carbonate needs stomach acid to be absorbed
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
Testosterone
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
distal convoluted tubules (DCT)
What class of drugs exhibit estrogen antagonist and agonist properties in a tissue-specific manner?
Selective estrogen receptor modulators (SERMs)
What SERM has estrogen AGONIST activity on bone, which decreases bone resorption and improves bone density?
Raloxifene
What SERM has estrogen ANTAGONISTIC effect on breast tissue and can decrease the risk of breast cancer?
Raloxifene
What SERM has estrogen ANTAGONISTIC effect on uterus and does not increase the risk of endometrial cancer?
Raloxifene
The NFκB (RANK) and RANK-L (ligand) interaction is essential for the formation and differentiation of
Osteoclasts
What regulatory factor blocks the binding of RANK-L to RANK and ↓ formation of mature osteoclasts, leading to ↓ bone resorption?
Osteoprotegerin (OPG)
Low estrogen level causes osteoporosis by decreasing ________ production, increasing RANKL-RANK binding in osteoclast precursors
Osteoprotegerin (OPG)
A monoclonal antibody used in the Tx of postmenopausal osteoporosis that binds to RANKL to inhibit its binding to RANK receptor on osteoclasts
Denosumab
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?
Bisphosphonates
The most common side effect of Bisphosphonate that can be avoided by swallowing the medication with enough water + maintaining upright position for 30 minutes
Esophagitis
