MSK/Derm Flashcards
[Osteogenesis]
1. Intramembranous ossification
A. Process
B. Bones formed from this process
- Endochondral ossification
1A. Intramembranous ossification - bone tissue laid down directly in embryonic connective tissue or mesenchyme
- mesenchyme condenses within vascularized collagen matrix
- mesenchymal stem cells differentiate into osteoblasts (via Sox9, Runx2)
- osteoblasts secrete bone matrix –> woven bone
- woven bone (immature) remodeled into lamellar
B. Forms membranous flat bones of the head (skull, midface, jaw) + clavicle
2A. Endochondral ossification - bone tissue replaces preexisting hyaline cartilage
- mesenchymal condensation
- chondrocytes differentiate –> Type 2 Collagen = cartilage
- chondrocytes hypertrophy –> Type 10 collagen (in fetal cartilage)
- primary ossification center forms with artery bringing pre-osteoblast cells; bone matrix formation –> Type 1 collagen (bone)
B. Bones of limbs and girdle
[Osteogenesis]
- Differentiate cortical vs trabecular bone
- Differentiate osteoblasts vs osteocytes vs osteoclasts
1A. Cortical (compact) bone - long bone shafts with concentric layers of mineralized collagen; outer periosteal and inner endosteal surface
- functional unit is osteon
- hard, strong, and stiff to support body
B. trabecular (cancellous, spongy) bone - axial skeleton and ends of long bones with interconnecting meshwork of rods and plates
- functional unit is trabecula
- highly vascular
2A. osteoblasts - on surfaces of bone matrix
- synthesize bone matrix –> osteoid (type I collagen + GAGs + osteopontin), hydroxyapatite
- regulate osteoclastogenesis (via RANKL and OPG)
- communicate with osteocytes
- derived from mesenchyme
B. osteocytes - 90% of adult bone cells, derived from osteoblasts
- communicate with osteoblasts - mechanical function to sense stress and stimulate anabolism
C. osteoclasts - secrete H+ to dissolve mineral of bone matrix (hydroxyapatite) and resorb bone
- multi-nucleated; derived from hematopoietic progenitors (circulating monocytes)
- require RANKL and M-CSF for maturation
[Osteogenesis]
- Camptomelic dysplasia
- Cleidocranial dysplasia
- Achondroplasia
- Camptomelic dysplasia - AD Sox9 mutation (regulates commitment to chondrogenic lineage)
- short-limbed dwarfism and neonatal death - Cleidocranial dysplasia - AD Runx2 mutation (regulates commitment to osteoblast lineage)–> cartilage skeleton but no bone; no clavicles
- Achondroplasia - AD gain of function mutation in fibroblast growth factor 3 receptor (FGFR3) at paternal allele–> inhibits chondrocyte growth and induces terminal differentiation of endochondral ossification
- most common cause of short-limb dwarfism
- normal head with frontal bossing, torso normal size
- associated with advanced paternal age
- full penetrance; majority are new gene mutations
[Osteogenesis] 1. Osteogenesis imperfecta A. Cause B. Type 1 vs Type 2 C. Clinical
- Osteogenesis imperfecta “brittle bone disease”
A. Cause - Type 1 collagen mutations most commonly COLIA1 and COLIA2
i. Qualitative - misfolding, problems forming triple helix
ii. Quantitative - ↓ production of normal Type 1 collagen in bone, dentin, cornea
B. Type 1 vs Type 2
Type 1 - most common form; quantitative defect due to AD autosomal dominant mutations
Type 2 - due to qualitative defect; skeletal deformity with intrauterine fractures
C. Clinical
i. Type 1 can be confused with child abuse
- normal stature but multiple fractures with minimal trauma
- blue sclera (thin, can see choroidal vessels below)
- hearing loss (abnormal ossicles)
- tooth abnormalities, wear easily due to lack of dentin (dentinogenesis imperfecta)
ii. Type 2 - perinatal lethal
[Osteogenesis] 2. Osteopetrosis A. Cause B. Pathogenesis C. Clinical D. Treatment
- Osteopetrosis “Marble bone disease”
A. Cause - genetic defects in RANKL, RANK, OPG, carbonic anhydrase 2 –> latter impairs ability to create acidic environment for resorption
B. Pathogenesis - failure of osteoclasts to resorb bone –> thickened, dense bone that is prone to fracture
- bone fills marrow space –> pancytopenia, extramedullary hematopoiesis
C. Clinical
- bone-in-bone appearance on X-rays e.g. Ehrlenmeyer flask deformity of femur
- bone fractures
- cranial nerve impingement –> narrowed foramina –> palsies, vision and hearing impairment
- Type II renal tubular acidosis (carbonic anhydrase mutation) –> loss of bicarb in urine
D. Treatment - bone marrow transplant is curative (osteoclasts are derived from monocytes)
[Bone tumors]
Describe including locations, histology, and clinical features
1. Metastases
2. Osteoma
- Metastases - most common malignant tumors involving bone; typically involve axial skeleton, femur, humerus (due to red marrow in these areas)
“Permanently Relocated Tumors Like Bone”–>
- Prostate osteoblastic
- Renal
- Thyroid/testes
- Lung
- Breast - Osteoma - benign tumors
A. Location - masses (exophytic lesions) attached to membranous bone surface –> facial bones, skull
B. Histology made of mature lamellar bone (but no fibrous component)
C. Clinical - solitary, slow-growing, clinically silent unless it obstructs and causes problems with breathing, vision, hearing
- Gardner syndrome = FAP + soft tissue syndrome (multiple osteomas) + impacted teeth
[Bone tumors] Describe including locations, histology, and clinical features 3. Osteoid osteoma 4. Osteoblastoma 5. Osteosarcoma
- Osteoid osteoma - benign tumors <2 cm
A. Location - occur <25 yo in cortex of the shafts of long bone –> femur
B. Histology - woven bone rimmed by osteoblasts –> produce excess PGE2 –> pain
C. Clinical - chronic aching, intense pain that is worse at night and highly responsive to oral salicylates (aspirin)
- X-ray - central lucency surrounded by halo of radiodense reactive cortical bone - Osteoblastoma - similar to osteoid osteoma in age (<20 yo) and histology but are larger, arise in vertebral spinal column, and unresponsive to salicylates
- – - Osteosarcoma - most common primary malignant bone tumor most common bone neoplasia = multiple myeloma
- germline mutations - Rb and Li-Fraumeni (p53)
- M»F
A. Location - long bones near growth plates (metaphysis) –> distal femur / proximal tibia (knee area), proximal humerus (shoulder area)
bimodal distribution:
i. Primary (75%) - 10-20 yo (due to rapid bone growth) –> metaphyses adjacent to growth plate of long bones
ii. Secondary (25%) - >65 yo with known risk factors (Paget’s, bone infarct, irradiation)
B. Histology - malignant spindle cells with mitotic figures making their own osteoid
C. Clinical - chronic pain - sometimes swelling, palpable mass (with pulsations)
- decreased ROM
- “sunburst” appearance and Codman triangle on X-Ray –> tumor destroying cortex and lifting periosteum
- NOT common - fractures, systemic symptoms
[Bone tumors]
Describe including locations, histology, and clinical features
1. Ostechondroma
2. Multiple hereditary osteochondroma
- Ostechondroma aka exostosis
A. Location - arise at metaphysis near growth plate of long bones, especially near the knee
- males < 25 years old
B. Histology - solitary, cartilage-capped tumor attached by bony stalk to underlying skeleton
- cartilage cap looks like disorganized growth plate
C. Clinical - mostly asymptomatic, due to slow-growing mass
- most common benign bone tumor
- rarely transforms to osteochondroma
- –
- Multiple hereditary osteochondroma
A. Location - near the knee, multiple lesions that develop in childhood
B. Histology - same as osteochondroma
- chondrocyte differentiation disrupted –> abnormal cartilage growth
C. Clinical - bones may be bowed and shortened
- ↑ risk chondrosarcoma
[Bone tumors]
Describe including locations, histology, and clinical features
3. Enchondroma
4. Chondrosarcoma
- Enchondroma - benign neoplasm of hyaline cartilage
A. Location - centrally located in medullary cavity of long bones esp metaphyses of short tubular bones of hands and feet
B. Histology - nodules of hyaline cartilage rimmed by narrow band of reactive bone
- not infiltrative, no mitotic figures
- well-defined, lucent with internal mineralization on X-ray *must exclude chondrosarcoma (look radiologically similar)
- Chondrosarcoma
A. Location - mostly primary lesions, secondary is preexisting lesion (Paget, radiation)
- axial skeleton - pelvis, axial skeleton (eg femur), and ribs
- older age - 60+ yo
B. Histology - produces exclusively cartilage
- endosteal scalloping, calcified matrix on X-ray
C. Clinical - painful, progressively enlarging mass
[Bone tumors]
Describe including locations, histology, and clinical features
5. Ewing Sarcoma
- Ewing Sarcoma - primary malignant tumors of bone and soft tissue
A. Location - arises in medullary cavity (diaphysis) and invades cortex, periosteum, and soft tissue
- diaphysis of long tubular bones chondrosarcoma, osteosarcoma occur along the joint
- boys < 15 years old, whites > blacks
- t(11;22) translocation
B. Histology - derived from neural crest and mesenchymal stem cells
- anaplastic small blue cell malignant tumor
- Homer-Wright rosettes (tumor cells arranged in circle about neuropil) –> indicates neural differentiation (seen in other tumors of children eg medulloblastoma, neuroblastoma)
- X-ray shows lytic tumor extending into soft tissue
- periosteal reaction –> layers of reactive bone deposited in “onion skin” fashion
C. Clinical - painful enlarging mass that is tender, warm, swollen
- systemic findings - fever, anemia, ↑ ESR, anemia
- extremely aggressive with early mets but responds to chemo (actinomycin D)
[Bone tumors]
Describe including locations, histology, and clinical features
6. Giant cell tumor
- Giant cell tumor = osteoclastoma
A. Location - arise in the knee at the epiphysis
- lytic lesion with soap bubble appearance on X-ray
B. Histology - neoplastic cells are osteoblasts –> make large amount of RANKL –> stimulates osteoclast proliferation and differentiation –> highly destructive resorption of bone matrix
C. Clinical - arthritis, pathologic fracture
- locally aggressive benign tumor
- 20-40 years old
[Bone tumors]
- Fibrous cortical defects
- Fibrous dysplasia
- Fibrous cortical defects - developmental defects in children; metaphysis of distal femur/proximal tibia (knee area)
- asymptomatic, spontaneously remodeled to normal bone
- storiform (whorls of spindled fibroblast-like cells) with scattered osteoclast-like giant cells - Fibrous dysplasia - benign tumor –> localized development arrest - all components of bone present but do not mature (arise during skeletal growth and development)
- intramedullary, well-circumscribed, trabeculae of woven bone that does not develop into solid lamellar bone
- can be monostotic or polystotic (involve multiple bones),
or part of McCune-Albright Syndrome - cafe au lait skin pigmentations, polyostotic fibrous dysplasia, and endocrine abnormalities, and precocious puberty
[Review upper extremity lecture] Upper extremity nerves - causes of injury and presentation 1. Axillary 2. Musculocutaneous 3. Radial
- Axillary (C5-C6) –> innervates deltoid, sensation to skin overlying deltoid
A. Causes - anterior shoulder dislocation, fracture of surgical neck of humerus
B. Clinical - flattened deltoid, loss of sensation over deltoid
- associated with posterior circumflex artery - Musculocutaneous (C5-C7) –> innervates corachobrachialis, biceps, brachialis
A. Causes - upper trunk compression
B. Clinical - loss of forearm flexion and supination, loss of sensation over lateral forearm - Radial (C5-T1) –> innervates posterior muscles of forearm (triceps, brachioradialis)
A. Causes - compression of axilla (Sat night palsy, crutch injury); midshaft fracture of humerus, radial head subluxation (pulled elbow on child tearing annular ligament), dorsal wrist laceration eg handcuffs (only sensory loss)
B. Clinical *depends on location of injury
- loss of elbow extension
- loss of wrist extension –> wrist drop
- loss of thumb, finger extension
- loss of sensation over posterior forearm and dorsal hand
- associated with deep brachial artery
[Review upper extremity lecture] Upper extremity nerves - causes of injury and presentation 4. Median 5. Recurrent branch of median nerve 6. Ulnar
- Median (C5-T1)
A. Causes - median nerve runs through antecubital fossa; supracondylar fracture of humerus (more commonly pediatric), carpal tunnel syndrome, wrist laceration, FOOSH (lunate dislocation, Colles’ fracture)
B. Clinical
- weak wrist flexion with ulnar deviation (adduction), loss of pronation
- loss of thumb opposition –> atrophy of thenar eminence + “ape hand”
- (elbow injury) loss of flexion of digits 2 and 3 –> “sign of benediction” on trying to make a fist
- (wrist injury) loss of 1st and 2nd lumbricals –> “median claw” of digits 2 and 3 on resting
- loss of sensation over lateral palm of hand - Recurrent branch of median nerve
A. Causes - superficial laceration of palm
B. Clinical - ape hand, atrophy of thenar muscles (OAF), no loss of sensation
*thenar eminence sensation is also spared in carpal tunnel syndrome (atrophy of LOAF muscles) - Ulnar (C8-T1)
A. Causes - ulnar nerve runs through cubital tunnel; dislocation of elbow with posterior dislocation of ulna, fracture of medial epicondyle (funny bone), fracture of hook of hamate (FOOSH)
B. Clinical -
- (proximal injury) loss of lumbricals 3 + 4 –> “ulnar claw” on digit extension / at rest; radial deviation on wrist flexion (abduction)
- (elbow injury) weakness in wrist flexion / adduction
- loss of finger abduction and adduction (interossei)
- loss of thumb adduction, hypothenar atrophy
[Review upper extremity lecture] Brachial plexus lesions - innervations, causes, muscle deficit, and clinical condition 1. Long thoracic nerve 2. Upper trunk 3. Lower trunk
- Long thoracic nerve (C5-C7) –> innervates serratus anterior muscle
A. Causes - surgical (Axillary node dissection after mastectomy), stab wounds
B. Clinical - winged scapula –> cannot abduct abduct arm above horizontal position - Upper trunk (C5-C6)
A. Causes - lateral traction on neck during delivery (infants), motorcycle fall (adults)
B. Clinical - “waiter’s tip”
- arm adducted / hangs by side (deltoid, supraspinatus - abduction)
- arm medially rotated (infraspinatus - lateral rotation)
- arm extended, forearm pronated (biceps - flexion, supination) - Lower trunk (C8-T1)
A. Causes - upward force on arm during delivery (infants), grabbing tree branch to break fall (adults)
B. Clinical - loss of all intrinsic hand muscles (loss of median and ulnar nerve) –> “Klumpke palsy” –> total claw hand –> extension of MCP and flexion of PIP and DIPs
[Review lower extremity lecture] Innervations, causes, muscle deficits, clinical condition 1. Femoral nerve 2. Obturator nerve 3. Superior gluteal nerve 4. Inferior gluteal nerve
- Femoral nerve (L2-L4)
A. Innervations - muscles of anterior thigh
- quads –> knee extension
- iliopsoas, pectineus, sartorius –> hip flexion
B. Causes - rare, pelvic fracture or spontaneous retroperitoneal hematoma
C. Clinical
- loss of sensation over anterior thigh and medial leg (L4 is over the knee)
- loss of hip flexion and knee extension –> “quadriceps gait” where you put pressure on thigh to take next step (otherwise your knees buckle) - Obturator nerve (L2-L4)
A. Innervations - muscles of medial thigh
- adductors (longus, brevis, magnus), gracilis, obturator externus –> hip/thigh adduction
B. Causes - pelvic surgery
C. Clinical - leads to medial thigh wasting and groin pain, loss of hip adduction - Superior gluteal nerve (L4-S1)
A. Innervations
- gluteus medius and minimus –> hip abduction
- tensor fascia latae –> hip flexor
B. Causes - IM injection (should do superolateral quadrant to avoid injury)
C. Clinical - leads to positive Trendelenberg sign - opposite side pelvic drop when standing on one foot bc gluteus medius and minimus cannot keep pelvis level - Inferior gluteal nerve (L5-S2)
A. Innervations - gluteus maximus –> hip extension
B. Causes - iatrogenic, posterior hip dislocation (passive internal rotation)
C. Clinical - leads to gluteus maximus gait –> lurch backwards on heel strike; difficulty rising from seated position, climbing stairs
[Review lower extremity lecture] Innervations, causes, muscle deficits, clinical condition 1. Sciatic nerve 2. Common peroneal nerve 3. Tibial nerve
- Sciatic nerve (L4-S3) tibial + common peroneal nerve, which separate proximal to popliteal fossa
A. Innervations - muscles of posterior thigh
- hamstrings (Semitendinosus, semimembranosus, biceps femoris) –> knee flexion
B. Causes - posterior hip dislocation (passive internal rotation), hip replacement surgery
C. Clinical - weak knee flexion, knee hyper-extends while walking (polio gait)
- leads to loss of ankle DTRs, loss of achilles reflex, wasting of calf muscles - Common peroneal / fibular (L4-S2) *most common LE injury
A. Innervations - anterolateral compartments of leg
- lateral (superficial nerve) –> everts foot, sensory to dorsum of foot
- anterior (deep nerve) –> dorsiflexes foot, extends toes *injured in anterior compartment syndrome
B. Causes - fibular neck fracture, lateral blow to knee, leg cast, stirrups
C. Clinical - “steppage gait” foot drop
- loss of sensation to dorsum of foot - Tibial (L4-S3)
A. Innervations - posterior compartment of leg + muscles of foot
- gastrocnemius, soleus (triceps surae / calf muscle) + plantaris –> plantarflex foot, inverts foot
- flexor muscles of foot –> flex and abduct toes
B. Causes - rare, baker cyst or knee trauma
C. Clinical - foot is everted and dorsiflexed (can’t stand on tiptoes)
- loss of sensation to sole of foot (plantar foot)
[Review lower extremity lecture] Knee injuries incl causes + tests / findings 1. ACL 2. PCL 3. MCL 4. LCL 5. Unhappy triad
- ACL (attaches lateral femoral condyle to anterior tibia)
A. Cause - deceleration, noncontact injury with “pop”
B. Findings
- anterior drawer test (90 angle) - tibia moves anteriorly
- lachman (30 degrees) - PCL (attaches medial femoral condyle to posterior tibia)
A. Cause - fall onto / contact with flexed knee with “pop”
B. Findings
- posterior drawer + lachman tests - tibia moves posteriorly / femur slides forward - MCL
A. Cause - valgus lateral force (abduction)
B. Findings - abnormal passive abduction - LCL
A. Cause - varus force (adduction)
B. Findings - abnormal passive adduction - Unhappy triad - common injury in contact sports
A. Cause - lateral force applied to planted leg
B. Findings - damages ACL, MCL, and meniscus
[Myopathies]
Inflammatory idiopathic myopathies including epi, cause, histology, and clinical presentation
- Dermatomyositis
- Dermatomyositis
A. Epi - affects adults F>M, associated with ↑ risk carcinoma
B. Cause - autoantibodies anti-Jo1 and anti-Mi2, ANA (+) –> complement-mediated capillary injury, target blood vessels (which are in perimysium) –> lymphocytic invasion with CD4+ T cells in perimysium
C. Histology - perifascicular atrophy
- ↑ CK (>10x normal) - detects muscle damage / inflammation
- increased lactate dehydrogenase
D. Clinical
i. proximal, symmetric muscle weakness –> trouble climbing stairs, rising from seated position, raising arms; head drop, dysphagia
ii. cutaneous
- purple rash of upper eyelids (heliotrope rash)
- red papules on extensor surfaces (Gottron papules)
- sun-exposed, photosensitive rash
iii. systemic - interstitial lung disease, mechanic’s hands (cracking of finger pad skin)
[Myopathies]
Inflammatory idiopathic myopathies including epi, cause, histology, and clinical presentation
- Polymyositis
- Inclusion body myositis
- Polymyositis
A. Epi - F>M, diagnosis of exclusion
B. Cause - anti-Jo-1 Ab –> lymphocytic invasion with CD8+ T cells in endomysium; muscle fibers express MHC Class I
C. Histology - necrosis of muscle fibers
- ↑ CK (>10x normal)
- increased lactate dehydrogenase
D. Clinical - same as dermatomyositis (proximal symmetric muscle weakness, mechanic’s hands, interstitial lung disease) MINUS the cutaneous involvement - Inclusion body myositis
A. Epi - older men
B. Cause - idiopathic, no autoAb
C. Histology - CD8+ T cells in endomysium (like in polymyositis)
- muscle fibers contain vacuoles and abnormal cytoplasmic inclusions that have proteins associated with neurodegenerative disease
D. Clinical - asymmetric muscle weakness; starts in distal upper extremities (eg forearms), distal anterior compartment leg muscles, and quads
[Myopathies]
Muscular dystrophy including epi, cause, histology, and clinical presentation
1. Duchenne MD
2. Becker MD
- Duchenne muscular dystrophy
A. Epi - presents in childhood (not infancy)
B. Cause - X-linked recessive mutations in dystrophin (provides mechanical support for muscle cells that interact with ECM) –> muscle fibers degenerate with loss of support
- Duchenne MD - deletion of dystrophin due to frameshift mutation
C. Histology - segmental myofiber degeneration and fatty replacement with adipose tissue
- ↑ CK (detects muscle inflammation / damage)
D. Clinical - weakness, proximal and lower, then distal and upper extremities
- calf pseudohypertrophy (thick but mostly fat)
- Gower’s sign - need to use upper extremities to get up off the floor
- cardiac dysfunction (involves myocardium) - shorter life expectancy, death from cardiac or respiratory failure
- –
- Becker
A. Epi - same
B. Cause - X-linked recessive, mutated dystrophin
C. Histology - same
D. Clinical - presents later and with milder symptoms
[Myopathies]
Muscular dystrophy including epi, cause, histology, and clinical presentation
3. Myotonic dystrophy
- Myotonic dystrophy
A. Epi - onset in early adulthood
B. Cause - AD inherited trinucleotide repeat of CTG in 3’ untranslated region of DMPK gene –> creates 3’ hairpin loop –> sequesters RNA binding and splicing proteins from nearby genes –>
- full mutation > 50 CTG repeats
- both parents can transmit, but most severe form is inherited from mother
C. Histology -
D. Clinical
i. Mild - mild myotonia, cataracts
ii. Classic DM1 (50-1000 repeats) - adult-onset muscular dystrophy (muscle wasting and weakness) +
- myotonia (inability to relax voluntary muscle after vigorous effort)
- cataracts
- balding
- cardiac conduction defects (cardiomyopathy)
- insulin resistance –> DM2
iii. Severe - infantile hypotonia
[Neuromuscular junction disorders] Myasthenia gravis 1. Epi 2. Pathophysiology 3. Clinical 4. Triggers 5. Treatment
Myasthenia gravis
1. Epi - F>M, bimodal age peak, autoimmune
- Cause / Pathophysiology - Ab that target ACh nicotinic postsynaptic receptors –> compete with ACh for receptors –> bind, cross-link, and endocytose receptors –> damage postsynaptic muscle membrane
- Clinical - specific muscle weakness that worsens with repeated muscle use / stimulation –> worsens throughout the day; normal DTRs
- first is extraocular muscle weakness –> diplopia, ptosis
- then spreads from ocular –> facial –> bulbar –> truncal –> limb muscles
- bulbar muscle weakness (with MuSK Ab) –> speech, swallowing problems
- associated with thymic hyperplasia or thymoma (thymus = where T cells mature) - Triggers - emotional stress, menstruation, viral infection, bright sunlight
- Treatment - pyridostigmine, neostigmine (Anticholinesterase inhibitor) –> more ACh to compete with the Abs –> symptom relief
[Neuromuscular junction disorders] Lambert-Eaton Myasthenic Syndrome 1. Epi 2. Pathophysiology 3. Clinical 4. Treatment
Lambert-Eaton Myasthenic Syndrome
- Epi - paraneoplastic - associated with small cell lung cancer (cancer expresses calcium channels) –> M>F, in smokers
- or can be autoimmune (F>M, no correlation with smoking) - Pathophysiology - Ab against voltage-gated Calcium channels on presynaptic motor nerve terminal –> inhibits Ca2+ influx –> diminished neurotransmitter release
- Clinical - proximal muscle weakness - for months to years –> decreased DTRs, difficulty climbing stairs, walking
* muscle weakness improves with use (opposite of MG)
- eyes are usually spared
- autonomic sx - dry mouth, constipation, erectile dysfunction, dry eyes - Treatment - search for small cell lung cancer
- anticholinesterase agents do not improve symptoms
- aminopyridines - block K+ channels –> allow depolarization to last longer –> more ACh released from terminal