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
[Neuromuscular junction disorders] Organophosphate poisoning 1. Epi 2. Pathophysiology 3. Clinical 4. Treatment
Organophosphate poisoning
1. Epi - worldwide usage as insecticides
- Pathophys - bind to acetylcholinesterase –> prevents acetylcholine from being broken down
- sarin gas has same MOA
3. Clinical - cholinergic excess --> DUMBELS D-diarrhea U-urination M-miosis B-bradycardia, bronchoconstriction E-emesis L-lacrimation S-salivation
- Treatment -
- pralidoxime –> acute antidote; displace organophosphates to prevent aging (irreversible inhibition of acetylcholinesterase) and regenerate AChE
- atropine - blocks ACh interaction with receptor
[Osteoarthritis] Osteoarthritis 1. Epi / risk factors 2. Pathophysiology 3. Pathologic features 4. Clinical presentation
Osteoarthritis
- Epi - most common joint disease
- risk factors - age, female, obesity (knee), joint trauma or microtrauma
- commonly affects knees, hips, hands, spine - Pathophys - damage to normal articular cartilage –> chondrocyte repair with defective cartilage –> abnormal joint loading –> cracking, fracturing of cartilage
- histology - fibrillation of cartilage (small fractures) - Pathologic features
A. osteophytes (bone spurs)
B. joint space narrowing due to increased subchondral bone (sclerosis)
C. subchondral bone cysts (synovial fluid forced through fibrillated cartilage into exposed bone)
D. joint mice - dislodged pieces of cartilage and bone
E. eburnation - complete loss of cartilage –> bone on bone –> bone becomes polished like ivory - Clinical - swollen, hard joints
- symptoms and signs related to damage, not inflammation (no inflammatory synovial fluid)
- <30 min morning stiffness
- pain increases with use (ie at end of day)
- asymmetric and slowly progressive - only few joints symptomatic
- deep, dull aching pain
- NO systemic symptoms (fever, anemia, weight loss)
[Osteoarthritis] Risk factors and diagnosis of the following types of osteoarthritis: 1. Knee 2. Hip 3. Hand
- Knee
A. Risk factors - obesity (weight-bearing joint), age
B. Diagnosis - can diagnose without X-rays
- symptoms: knee pain, functional limitation, AM stiffness
- signs: crepitus, decreased ROM, bony enlargement
- medial cartilage lost first –> varus stress –> bow-legged - Hip
A. Risk factors -
- avascular necrosis of femoral head (medial circumflex femoral artery) - due to corticosteroids, alcohol, sickle cell, trauma
- Legg-Calve-Perthes (idiopathic avascular necrosis of femoral head in obese male children)
- slipped capital femoral epiphysis (in obese male children)
B. Diagnosis - hip pain + at least 2 of following:
- passive external rotation –> decreased ROM and pain on internal rotation
*passive internal rotation –> posterior hip dislocation
- low RBC sedimentation rate (no inflammation)
- X-ray showing osteophytes and joint space narrowing - Hand
A. Risk factors - female, age
B. Diagnosis - involves PIP (Bouchard nodes) and DIP (Heberden nodes)
*prOximal - BOuchard
[Rheumatoid arthritis] RA 1. Epi / risk factors 2. Pathophysiology 3. Diagnosis
Rheumatoid arthritis
- Epi / risk factors - most common persistent inflammatory arthritis
- female middle-aged (autoimmune)
- genetics: HLA-DR4, family history
- environmental: smoking, silica - Pathophysiology - autoimmune Type IV HSN
- anti-cyclic citrullinated peptide antibodies ACPA –> inflammatory cells infiltrate synovial membrane –> CD4+ T cells stimulate B cells and macrophages:
- B cells produce rheumatoid factor (IgM Ab against patient’s IgG Fc region)
- macrophages produce TNFalpha –> pro-inflammatory cytokines
- -> formation of pannus (synovium becomes thickened with villous projections) –> erodes bone and cartilage - Diagnosis
- antibodies: rheumatoid factor, ACPA (more specific), ANA
- non-specific inflammation markers: ESR, C-reactive protein
- hematologic: anemia of chronic disease
[Rheumatoid arthritis] RA 4. Pathologic features 5. Clinical presentation 6. Extra-articular manifestations
- Pathologic features
- osteopenia adjacent to joint (Decreased bone mass but not to the extent of osteoporosis)
- proliferative synovitis with inflammatory infiltrate (lymphocytes, macrophages) –> activates osteoclasts –> osteoporosis (bone loss –> Decreased bone mass)
- deformities: ulnar finger deviation, swan neck (PIP extension, DIP flexion), boutonniere (PIP flexion, DIP extension)
- cervical subluxation - esp with neck flexion, C1-C2 vulnerable bc affects upper cervical spine - Clinical presentation - swollen, boggy joints (due to swelling, tenderness, warmth)
- systemic symptoms (fever, weight loss, fatigue) due to cytokine release
- morning stiffness (~1 hour) and pain that improve with use
- symmetric - affects upper cervical spine and small joints of hands and feet, esp MCP and PIP but not DIPs - Extra-articular manifestations
- rheumatoid nodules (central fibrinoid necrosis with palisading macrophages) on extensor surfaces e.g. olecranon, proximal ulna
Caplan syndrome = pneumoconiosis + rheumatoid nodules in lung
- cardiac - pericardial effusion, pericarditis
- pulmonary - pleuritis, effusions, interstitial lung disease
- ocular - dry eye, Sjogren’s
- Felty syndrome - SANTA –> Splenomegaly, Anemia of chronic disease, Neutropenia, Thrombocytopenia, + Arthritis (rheumatoid)
[Paget disease]
- Epi / risk factors
- Pathophysiology
- Pathologic features
- Clinical
- Treatment
- Complications
Paget Disease - focal disorder of bone metabolism
- Epi - onset in old age
- risk factors: western european descent, age, M>F
- etiology unknown, perhaps viral (paramyxovirus) - Pathophysiology
A. Osteolytic stage - osteoclast»_space; osteoblast activity; osteoclasts hyper-responsive to D3, RANKL and have more nuclei than usual (up to 100)
B. Mixed - osteoclast and osteoblast activity
C. Osteosclerotic - osteoblasts make thick, sclerotic bone that fractures easily - Pathologic features
- main sites are pelvis, skull, lumbar spine, femur
- isolated ↑ ALP (normal GGT, calcium, phosphate, PTH, Vitamin D)
- “jigsaw” mosaic pattern of woven and lamellar bone (rapid bone turnover) that is disorganized, poorly mineralized, lacks structural integrity - Clinical
- most patients are asymptomatic
- pain due to bone overgrowth and microfractures
- deformity –> bowing of limb, increased skull size (hat size enlarged), lion-like facies
- hearing loss due to auditory foramen narrowing (temporal bone) - Treatment
- bisphosphonates (induce osteoclast apoptosis and block osteoclast activity, but can lead to osteonecrosis of the jaw) - Complications
- high output heart failure - due to formation of AV shunts in bone (Pagetic bone very vascular)
- ↑ risk osteosarcoma
[Bone/Joint infections] Septic arthritis 1. Risk factors 2. Etiology by age group 3. Diagnosis
Septic arthritis
- Risk factors - joints have hyaline cartilage –> susceptible to infection bc relatively avascular –> immune cells cannot access easily
- prosthetic joints
- elderly
- immunosuppressed
- previous joint pathology - RA, osteoarthritis, gout, sickle cell disease
2. Etiology A. children <2 yo --> H. influenza / Kingella (both are part of HACEK group - Gram (-) coccobacilli that also cause endocarditis) B. Young adults - Neisseria gonorrhea C. Adults - Staph aureus, epidermidis D. Sickle cell (any age) - salmonella
- Diagnosis - joint aspiration, DDx includes gout and pseudogout –> increased WBC count, no crystals
* immediate diagnosis necessary bc can rapidly destroy joint
