Musculoskeletal Flashcards
Growth of limbs vs growth of skull/chest bones?
Limbs = endochondral ossification (chrondrocyte activity)
skull/chest = intramembranous ossification
Body habitus of patients with achondroplasia
How does this happen?
(dwarfism): failure of endochondral ossification due to abnormal chondrocytes → short limbs; normal intramembranous ossification → normal head/chest size
Mutation in the FGFR3 gene, which causes exaggerated inhibition of chondrocyte proliferation
Autosomal dominant with full penetrance (homozygosity is lethal) – most mutations are sporadic with unaffected parents
Collagen type: tendons/ligaments
Type 1
Collagen type: scar tissue
Type 1
Collagen type: granulation tissue
Type 3
Collagen type: cartilage
Type 2 (car-two-lage)
Collagen type: cornea
Type 1
Collagen type: basement membrane
Type 4
Collagen type: vitreous humor
Type 2
Collagen type: vessels
Type 3
Most common cause of osteomyelitis?
Staph aureus
Most common cause of osteomyelitis in sickle cell anemia?
Salmonella
Most common cause of osteomyelitis in neonates?
H influenza
Most common cause of bacterial arthritis in young adults?
N gonorrhea
Most common overall cause of bacterial arthritis?
Staph aureus
Osteoprotegerin (OPG) effects
reduces osteoclast differentiation by blocking RANKL
Nuclear factor kappa B ligand effects on bone
(RANKL) Induces osteoclast differentiation
What factors induce osteoblast action?
Insulin growth factor (IGF)
TGF-B
Fibroblast growth factor (FGF)
Estrogen effects on bone
Promotes bone building!
Estrogen promotes production of OPG, which blocks RANKL from stimulating osteoclasts from resorbing bone. Also promotes apoptosis of osteoclasts.
Estrogen deficiency causes osteoporosis (menopause)
Denosumab
Used for treatment of osteoporosis
Monoclonal antibody against RANKL (prevents RANKL from stimulating osteoclast activity)→promotes bone strength
Bisphosphonates
Anti-resorptive agents that inhibit mature osteoclasts
Tamoxifen and Raloxifene
Selective estrogen receptor modulators (SERMs) used in breast cancer treatment
Act as estrogen agonists at bone – promote bone strength
Raloxifene is the better option because it does not act on endometrial receptors (Tamoxifene can promote endometrial hyperplasia)
Osteogenesis imperfecta common etiology/presentations
Congenital defect in type 1 collagen – impaired bone matrix formation
Defect in glycosylation or triple helix formation in collagen
Blue sclera: due to exposure of choroidal veins Hearing loss (fx of the bones of the middle ear) Bone fractures (usually without bruising)
Osteopetrosis: presentation and etiology
aka “marble bone disease” – failure of normal bone resorption due to abnormal osteoclasts → Causes thickened, dense bones that are prone to fracture
Usually due to a mutation in carbonic anhydrase II (prevents osteoclasts from creating an acidic environment that is necessary for bone resorption)
XR that shows a “bone in bone” appearance in a patient with nerve palsies?
Osteopetrosis: narrowing of the foramina causes cranial nerve palsies
Role of vitamin D in bone health?
Increased absorption of Calcium and phosphate in the intestines and enhancement of bone mineralization
Rickets
Vitamin D deficiency
Defective mineralization of osteoid due to lack of phosphate
(Dec vitamin D –> dec serum Ca –> inc PTH –> dec phosphate reabsorption in kidney (and inc calcium reabsorption)
Pathology of what disease shows a mosaic pattern of woven and lamellar bone
Paget disease: disordered and nonintegrated cycles of bone formation and resorption (inc osteoblast AND osteoclast activity), which causes a mosaic pattern of woven and lamellar bone.
Causes of avascular necrosis of the femoral head? What artery is effected?
Ischemia of the medial circumflex artery
ASEPTIC Alcoholism Sickle cell disease Endogenous/exogenous corticosteroid use Pancreatitis Trauma Idiopathic Caisson (the bends)
Also: gaucher disease and slipped capital femoral epiphysis
Lab values for osteoporosis?
All normal!! (serum calcium, phosphate, alk phos, PTH)
What causes elevated alkaline phosphatase in bone disorders?
Activation of osteoblasts (osteoblasts need an alkaline environment to build bone, whereas osteoclasts need an acidic environment to resorb bone)
What bone malignancy has a bimodal distribution?
Osteosarcoma. Affects mainly 10-20 year olds but also can affect those over 65
What does a sunburst pattern in a bone on XR indicate?
Osteosarcoma. Usually occurs around the knee area
What is the only bone tumor that arises from the epiphysis?
Giant Cell Tumor
“Interferes with the epiphysis, so kids won’t become giants!”
Which bone tumor has a soap bubble appearance on xray?
Giant cell tumor (a benign tumor of osteoclast origin). Shows multinucleated giant cells on histology.
Think of a giant taking a bubble bath
What types of patients does Ewing sarcoma typically effect?
Boys under 15
Ewing sarcoma
Anaplastic small blue cell malignant tumor
Neuroectodermal origin
Onion skin periosteal reaction in bone
t(11;22) causing fusion protein EWS-FL1
Arthritis of the DIP joints? PIP? MCP?
Osteoarthritis = DIP and PIP
Rheumatoid arthritis = PIP and MCP
Herberden nodes
Bouchard nodes
Boutonniere deformities
Herberden nodes = DIP, OA
Bouchard nodes = PIP, OA
Boutonniere deformities = RA
Patient presents with joint pain that worsens with activity throughout the day.
OA
Asymmetrical, osteophyte formation, subchondral cysts
Patient presents with joint pain that is present in the morning and improves with activity
RA
Symmetrical, pannus formation
Why does alcohol and meat consumption trigger gout?
Alcohol metabolites compete for the same excretion sites in the kidney as uric acid - leads to decreased uric acid secretion and buildup of it in the blood –> causing gout
Meat consumption brings in DNA and RNA into body which are metabolized to form a lot of uric acid
Rheumatoid factor
IgM against the Fc portion of IgG causes immune complex deposition and chronic inflammation
Diagnosis of RA
Anti-cyclic citrullinated peptide Ab (more specific for RA than rheumatoid factor)
What HLA is RA associated with?
HLADR4 (4 walls in a rheum)
Patient undergoing treatment for RA presents with oral lesions, hair loss, and elevated LFTs. What medication are they taking and what is the mechanism of action?
Methotrexate
Folate antimetabolite that targets rapidly proliferating cells by halting purine and pyrimidine synthesis through irreversible binding of DHF reductase.
Is toxic to other highly dividing cells (oral, GI, hair follicles)
What do you need to do before putting patients on Enteracept or Infliximab?
Important to evaluate for latent TB because Enteracept can cause reactivation (TNF is important in granuloma formation and stabilization)
Enteracept
anti-TNF a
Acts as a decoy TNFa receptor
Gout vs pseudogout crystals
Gout: monosodium urate, yellow under parallel light (Negative birefringence), needle shaped
Pseudogout: calcium pyrophosphate, blue under parallel light (positive birefringence), rhomboid shaped
Colchicine
Treatment of acute gout
Inhibits microtubular polymerization- prevents neutrophil chemotaxis, phagocytosis, and degranulation)
Side effects: Nausea, abd pain, diarrhea
Allopurinol
xanthine oxidase inhibitors: used for gout prophylaxis and long term treatment
Febuxostat
xanthine oxidase inhibitors: used for gout prophylaxis and long term treatment
Lesch-Nyhan syndrome
hyperuricemia (secondary gout) due to severe defect in hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
Presents with mental retardation and self mutilation
Poor life expectancy
X linked (hypoXanthine)
What are HLA are the seronegative spondylarthropathies associated with?
HLA-B27
Often occurs after an illness due to molecular mimicry
Patient presents with dactylitis (swollen fingers) and Xray shows a pencil in cup deformity?
Psoriatic arthritis
What joints are affected in ankylosing spondylitis? What are some of the disease sequelae?
Spine and sacroiliac joints
Uveitis
Aortic regurgitation (ascending aortitis)
Hypoventilation due to limited chest expansion
What bacteria can cause reactive arthritis (Reiter syndrome)? What are the major symptoms?
Can’t see, cant pee, cant bend my knee
(conjunctivitis, urethritis, arthritis)
Campylobacter Chlamydia Yersenia Shigella Salmonella
25 year old woman presents with widespread pain and is tender when you press in certain spots. She also complains of parasthesias. What do you suspect? What will you prescribe?
Fibromyalgia
SNRIs, TCAs, Gabapentin
What musculoskeletal condition is associated with temporal (giant cell) arteritis?
Polymyalgia rheumatica
Pain/stiffness of hips and shoudler with fever, myalgia, and weight loss. Inc ESR
A bands
I bands
Z bands
H band
A = dArk (contains thick and thin filaments) I = lIght (contains only thin filaments) Z = dark line within I band ( a sarcomere is Z band to Z band) H = only contains thick filaments
Effects of contraction on different bands
A band remains the same length (A band is Always the same)
Shortening of H and I bands and between Z lines (HIZ shrinkage)
Where is calcium stored in the muscle fiber
Sarcoplasmic reticulum. Released by activation of RyR1 calcium release channels
What drug(s) causes malignant hyperthermia? What drug is used to treat it?
Caused by succinylcholine (ACh agonist – causes unregulated release of calcium from the RyR1 channel in the sarcoplasmic reticulum)
Treated with dantrolene: prevents release of Ca2+ from the sarcoplasmic reticulum by binding to the ryanodine receptor
Mechanism of muscle contraction
Calcium (released from the sarcoplasmic reticulum) binds to troponin, which causes a conformational change and moves tropomyosin out of the myosin-binding site on actin filaments. This allows myosin (on thick filaments) to bind to actin (on the thin filament) and ATP allows thick filament to crawl along thin filament
]Rhabdomyolysis causes what electrolyte abnormality?
Hyperkalemia (potassium is released from the destroyed cells)
o Release of myoglobin is toxic to kidneys – acute tubular necrosis
Where is osteomyelitis most common in adults vs kids?
Adults = epiphysis Kids = metaphysis
Results of carbonic anhydrase II mutation
Osteopetrosis: unable to form H+ which is necessary to create an acidic environment for bone resorption
Renal tubular acidosis: unable to form H+ which is necessary so it can bind with NH3 to form NH4 in the tubule lumen for excretion of acid (causes metabolic acidosis)
How do joint deviations and fusions (ankylosis) occur in RA?
Synovial tissue gets inflamed and produces pannus (granulation tissue). The pannus contains myofibroblasts which cause contraction together of the joint (much like is seen in wound healing)
Uric acid is produced from…
Purine metabolism (Adenosine, Guanosine)
Anti-Jo-1 antibody
Dermatomyositis and polymyositis
anti-histidyl-tRNA sythetase
How can you differentiate between Dermatomyositis and Polymyositis?
Dermatomyositis has perimysial inflammation whereas polymyositis has endomysial inflammation.
“Perimysium is closer to the skin, which is effected in dermatomyositis)
Patient presents with recent bilateral arm weakness. You notice a rash over her eyelids and cheeks. She also has red papules over her knuckles and elbows. What do you suspect and what is this condition associated with in the future?
Dermatomyositis
Can be associated with cancers: ovarian, lung, colorectal, non Hodgkin lymphoma
In what conditions do you see malar rash? How can you distinguish between them?
Lupus and Dermatomyositis
Lupus: anti dsDNA antibody
Dermatomyositis: anti Jo 1 antibody
Genetic cause of Duchenne muscular dystrophy?
X linked
Deletion causing a frameshift mutation in the dystrophin gene (part of the skeletal muscle cytoskeleton)– causes widespread muscle necrosis and fibro-fatty replacement
Age of onset of Duchenne vs Becker muscular dystrophy
Duchenne - first year of life
Becker - young adults
Cause of myasthenia gravis
Autoantibodies against the postsynaptic acetylecholine receptor at the neuromuscular junction
25 year old male presents with difficulty loosening grip after a handshake or turning a doorknob. Exam shows muscle wasting on hands, testicular atrophy, cataracts, and frontal balding.
Myotonic dystrophy
AD inheritance: CTG trinucleotide repeat causing abnormal expression of myotonin protein kinase
Selective destruction of Type 1 muscle fibers
What type of hypersensitivity is Myasthenia gravis?
Type 2: production of auto-antibodies
What is myasthenia gravis associated with?
Thymoma
Lambert-Eaton Syndrome: cause and associations
Antibodies against presynaptic calcium channels of the neuromuscular junction
Arises as a paraneoplastic syndrome (small cell carcinoma of the lung)
Calcium binds to… troponin or tropomyosin
troponin
Injury to the anterior portion of the lateral leg can cause damage to what nerve(s)?
The common fibular nerve (wraps around the head and neck of the fibula)
aka common peroneal nerve
SS-A or SS-B antibodies
Anti nuclear antibodies
Sjogren’s syndrome
autoimmune disorder characterized by destruction of exocrine glands by lymphocytic infiltrates – dry eyes and mouth, joint pain
Carpal tunnel syndrome is entrapment of what nerve? What causes acute carpal tunnel?
Median nerve
Acute: dislocation of the lunate
Present with pain and tingling of the lateral three digits with decreased sensation
Muscles that make up the rotator cuff? Which one is most commonly injured?
SITS Subscapularis: internal rotation Infraspinatus: external rotation Teres minor: external rotation Supraspinatus: abduction
Supraspinatus is most commonly injured
What is the most commonly fractured wrist bone? What is a complication of this?
Scaphoid
Avascular necrosis
What nerve is in charge of motor function of the anterior arm?
Musculocutaneous: damage causes loss of forearm flexion and supination.
Patient presents with wrist drop
Radial nerve damage: unable to extend at the wrist
Use of crutches can cause damage to what nerve?
Radial nerve
Fracture of medial epicondyle causes damage to what nerve?
Ulnar nerve
Margins and contents of the carpal tunnel
Volar: flexor retinaculum (transverse carpal ligament)
Dorsal: carpal bones
Contents: the median nerve, the flexor digitorum profundus and superficialis, and the flexor pollicis longus
What causes keloid formation?
excessive scar formation due to production of excessive amounts of TGF-B without regulation.
o Collagen fibers are arranged in a disorganized fashion
Which interleukin is associated with giant cell arteritis?
IL 6
Medial vs lateral epicondylitis
Medial: due to repetitive wrist flexion (golfer’s elbow)
Lateral: due to repetitive wrist extension (tennis elbow)
o “Mother Fucker Let’s Eat!”
Which nerve root is damaged?
Loss of Achilles reflex
S1
Which nerve root is damaged?
Loss of patellar reflex
L4
Which nerve root is damaged?
Weakness of knee extension
L4
Which nerve root is damaged?
Weakness of dorsiflexion
L5
Which nerve root is damaged?
Weakness of plantarflexion
S1
McCune Albright Syndrome
due to mutation affecting G protein signaling which causes constitutive activation of the G protein/cAMP/adenylate cyclase signaling cascade – leading to gain of function in the affected cells
Unilateral café au lait spots, polyostotic fibrous dysplasia, (multiple osteolytic appearing lesions of the hip and pelvis), precocious puberty, multiple endocrine abnormalities
Only survivable if there is mosaicism
Why is it important to stay upright after taking a bisphosphonate like Alendronate?
Can cause esophageal erosion
What would happen if a person lacked T tubules?
**Uncoordinated contraction of individual fibers
T tubules are invaginations of the sarcolemma that extend into each muscle fiber, they transmit depolarization signals to the sarcoplasmic reticulum and trigger the release of calcium – the uniform distribution of T tubules ensures coordinated contraction of all myocytes
Collagen defect in osteogenesis imperfecta. Where does this normally take place?
Impaired glycosylation and formation of triple helix (normally takes place int he rER of fibroblasts)
Collagen defect in scurvy. Where does this normally take place?
Impaired hydroxylation of collagen due to lack of vitamin C (cofactor)
Normally takes place in the rER of fibroblasts
Collagen defect in Ehlers Danlos? Where does this normally take place?
Impaired cross linking of cartilage (crosslinkage between lysine and OH-lysine residues)
Normally takes place in the extracellular space
When there is a fracture to the clavicle bone, what causes the median segment to be displaced superiorly? What causes the lateral segment to be displaced inferiorly?
Superiorly: sternocleidomastoid
Inferiorly: pectoralis major and weight of the arm
Which autoantibody in SLE is associated with poor prognosis?
Anti-dsDNA (associated with renal disease)
Inflammatory cells in dermatomyositis and polymyositis?
Polymyositis = CD8+ cells
Dermatomyositis = CD4+ cells
What muscle can be used for breast reconstruction?
Latissimus dorsai
What can cause damage to the gluteus medius, resulting in trendelenburg gait?
• Can be caused by intramuscular injection into the superomedial quadrant that nerve injury –> Important to do injections into the superolateral quadrant of the gluteal region
Trendelenburg gait: the patient bends the trunk toward to side of the supporting limb due to weakness of the hip adductors (gluteus medius muscle) while the pelvis tilts away from the affected side
Nursemaid’s elbow
Radial head subluxation (nursemaid’s elbow): traction causes tearing of the annular ligament and it slips over the radius into the radiohumeral joint, where it is trapped
o Most common elbow injury in children
o Results from sharp pull on the hand while the forearm is pronated and elbow is extended
What is vulnerable to injury in the posterior triangle of the neck?
The spinal accessory nerve – innervates the trapezius which helps with abduction above the horizontal
