Achondroplasia is a defect in
cartilage = failure of long bone growth
Specific achondroplasia mutation
Autosomal Dominant Mutation of fibroblast growth factor receptor (FGFR)–short arm of chromosome 4
Achondroplasia presentation
Short arms and legs (endochondral ossificaiton), normal torso and head (intramembranous ossification is unaffected)
Osteogenesis imperfecta defect
AD mutation resulting in defective Type I collagen synthesis
The classic triad of OI- type 3
Multiple Fractures in strange places Blue sclera Hearing loss (inner ear bones Fx)
Examples of type 1 collagen
tendons, ligaments, the endomysium of myofibrils, interstitial stroma, the organic part of the bone, the dermis, the dentin, and organ capsules.
Labs for Osteopetrosis
Pancytopenia
2 Neuro complications of osteopetrosis
Vision/hearing impariment due to compression of nerves by foramina
Pathogenesis of osteopetrosis. Mechanism?
Lack of osteoclast function
Rickets/Osteomalacia defect
Excessive unmineralized osteoid; bad quality bone
MCC of Rickets/OM
Vitamin D deficiency
Osteomalacia lab values (Ca, Phos, PTH, Alk Phos)
Low Ca and Phos (low vitD) High PTH High Alk Phos (osteoblasts are driven by PTH. They are still working fine)
Osteoporosis is a reduction in
Trabecular bone mass (endosteal and periosteal resorption)
3 major Risk factors for osteoporosis
weight bearing exercise, menopause, Age
Effect of estrogen on bone development
Estrogen inhibits RANK, Loss of estrogen after menopause = more active osteoclasts
2 fracture-related complications of osteoporosis
Vertebral compression Fx Hip Fx
besides vertebral fractures which vertebral complications do osteoporosis pts have
Kyphosis and decreased height
Osteoporosis labs (Ca, Phos, PTH, alk phos)
All normal! Normal labs in the face of bone pain distinguishes this from osteomalacia
Paget disease of bone underlying problem
Imbalance b/w osteoblasts and osteoclasts (too much), viral infection, genetics
paget disease progression
Overactive osteoclasts –> osteoclasts start burning out –> osteoblasts activate –> lay down poor structure bone
A 58-year-old male patient reported to the dental hospital with a complaint of difficulty in vision.
History revealed that there were swellings in the skull bones, which started 6 years back. All swellings gradually increased in size. X-Ray skull attached. Diagnosis?
Pagets
4 classic SSx of paget’s disease of bone
Bone Pain Hearing loss/ Vision changes Increasing hat size Coarsening of facial features
Characteristic lab abnormality in paget’s disease
Isolated elevated ALk Phos with everything else normal
histology of paget’s
mosaic pattern of lamellar bone
2 major complications of paget disease
High output heart failure, Osteosarcoma
location of hematogenous osteomyelitis in kids (< 2 years) vs adults
Kids = epiphysis, Adults = metaphysis
MCC (most common cause) of osteomyelitis overall
S. aureus
MCC of osteomyelitis in diabetic or IV drug user
Psudomonas
MCC of osteomyelitis in sickel cell
salmonella typhi
Xray appearance of osteomyelitis
Lytic bone lesion surrounded by sclerosis (lytic lesion = sequstrum) (sclerosis = involurcrum)
The diagnosis is strongly suggested by the characteristic radiographic findings of a lytic focus of bone destruction surrounded by a zone of sclerosis.
Osteoma association
Gardner syndrome (FAP, fibromatosis, osteomas)
Osteoid osteoma is a tumor of
Osteoblasts
Gross appearance of osteoid osteoma
Tumor of osteoblasts surrounded by a ring of reactive bone
Osteoid osteoma imaging
Bony mass with a radiolucent core (osteioid from the osteoblasts)
Classic location of osteoid osteoma
Cortex of long bones
The classic presentation of osteoid osteoma
Humerus or femur pain that resolves with aspirin
Osteoblastoma location
Everything is the same as an ostoid osteoma, but it is located in the vertebra
Osteoblastoma presentation
Back pain that does not respond to aspirin (r/o osteoid osteoma)
diagnosis and location of origin
Osteochondroma arises from the lateral projection of the epiphyseal plate
Structure of osteochondroma
Bone with an overlying cartilage cap
Giant cell tumor location
Epiphysis of long bones. ONLY TUMOR IN THE EPIPHYSIS
Giant cell tumor is a proliferation of
Stromal cells
Xray of Giant cell tumor
“bubble” appearance of the epiphysis
osteosarcoma AKA
osteogenic sarcoma
Osteogenic sarcoma is a proliferation of
osteoblasts
primary osteosarcoma location
METAPHYSIS of long bones (unlike giant cell tumors)
3 major risk factors for sec. osteosarcoma
Paget Disease Radiation exposure LiFraumeni Sydnrome Gardner
diagnosis?
Xray of osteosarcoma
Ewing sarcoma is a proliferation of
neuroectodermal cells (poorly differentiated)
Ewing sarcoma location and population
Diaphysis of long bones in kids
Ewing sarcoma translocation
11:22
Xray of Ewing sarcoma
Onion skinning
mechanism of onion skinning
As tumor grows laterally, the periostium will continue forming new layers
chondrosarcoma location
pelvis or central skeleton
Osteoblastic bone metastasis
Prostate Cancer
Ewing sarcoma histology
malignant small blue cells
Articular cartilage is composed of
Type II collagen (hyaline)
The classic pattern of OA involvement
ASYMMETRIC involvement of Leg and hip joints + DIPs
Classic OA presentation
Morning stiffness that worsens with activity and improves with an NSAID
3 Xray findings of OA
Osteophytes UNILATERAL Joint space narrowing Subchondral sclerosis
RA HLA association
HLA DR4
Histology of RA
Pannus formation –> inflammed granulation tissue
Pathogenesis of RA, 3 steps
autoimmune synovial Inflammation –> pannus formation –> bony ankylosis (cartilage and bone damage)
Rheumatoid factor description
IgM against IgG
Most specific serum marker for RA
anti CCP (cyclic citrullinated peptide)
A pattern of joint involvement in RA
Symmetric involvement of PIPs, Wrists, elbows and knees NO DIP!
3 Extraarticular manifestations of RA
Rheumatoid Nodules Amyloidosis and synovial cysts
Rheumatoid nodule histology
Fibrinoid necrosis surrounded by palisading histocytes
cell type responsible for swan neck deformity
Myofibroblasts w/in the granulation tissue of the pannus and ossification
Xray of RA
BILATERAL joint space narrowing, and flexion-hyperextension abnormality
2 complications of RA
Anemia of chronic Dz (elevated hepcidin) Secondary amyloidosis (constant inflammation)
Type of pain in all seronegative spondyloarthropathies
Similar to RA. Worse in morning, improves with use
4 subtypes of seronegative spondyloarthropathies and their pattern of joint involvement (Symmetric vs Asymmetric)
HLA association :
PAIR ASAS Psoriatic (Asymmetric) Ankylosing spondylitis (Symmetric) Inflammatory Bowel Dz (Asymmetric) Reactive Arthritis (Symmetric)
HLA B27
Psoriatic arthritis x-ray finding
Other findings:
Pencil in cup deformity of DIP
Nail deformities
Ankylosing spondylitis joints involved
Spine and bilateral sacroiliac- may lead to vertebral fusion
Ank Spond Extraarticular manifestation
Uveitis
Reactive Arthritis (Reiter) triad
Conjunctivitis Urethritis Arthritis “Cant pee, cant see, cant climb a tree”
CLassic reactive arthritis case
2 weeks after GI or STD, pt presents with knee or low back pain
Joint fluid in reactive arthritis
Negative for infection
3 MCC septic arthritis
Staph Strep Gonorrhea
Atypical Triad of gonococcal arthritis
Polyarthralgia Tenosynoviits Dermatitis (pustules)
Joint fluid difference in Acute Gout vs Septic arthritis
Septic = purulent w/ WBCs but no crystals
Gout= WBCs + crystals
3 common causes of secondary gout
Leukemia/Myeloproliferative Disorders (increased cell turn over) Lesch Nyhan Renal insufficiency
Mechanism of Lesch Nyhan causing gout
HGPRT deficiency = no salvage pathway of purines = increased Purine metabolism into Uric Acid
What is the actual causative agent in Gout
Monosodium Urate Crystals
Major cellular mediator in gout flares
Neutrophils
histology/gross of tophi
Aggregates of crystals with fibrosis and giant cell reactions Essentially it is chronic granulomatous inflammation around the crystals (i.e. giant cells and fibrosis)
where are tophi located
soft tissues and joints
Gout synovial fluid analysis
Needle-shaped crystals with negative birefringence.
The crystals that turn yellow are the ones that are parallel to the light The ones that are blue are perpendicular
Crystals in pseudogout
Calcium pyrophosphate, rhomboid-shaped, blue
Fibromyalgia SSx
Widespread (not just proximal) PAIN w/o weakness Sleep problems Concentration problems
Polymyalgia rheumatica SSx
Proximal muscle pain WITHOUT weakness
3 Dermatomyositis SSx
Bilateral proximal muscle WEAKNESS, Rash Gottron papules
Ab to differentiate dermatomyositis from SLE (both cause malar rash and can have +ANA.
anti Jo1
Biopsy of dermatomyositis
Perimysial inflammation “perimysium is closest to the skin,
Dermatomyositis involves the skin with CD 4”:
Cell type involved in dermatomyositis
CD4 T cells
Biopsy of polymyositis
Endomysial inflammation
Cell type in polymyositis
CD8 poly = multiple…8 is more than 4…polymyositis has CD8. dermatomyositis has CD4
Myasthenia gravis effects on receptor
Competitive inhibition of post synaptic Ach receptor –> this is why high ACh can reverse sx
Association with MG
Thymic hyperplasia/thymoma Thymectomy will improve Non-MSK
Lambert Eaton defect
AutoAb to presynaptic Ca Channels, preventing Ach release
MCC of Lambert Eaton
Small cell lung cancer
How to differentiate MG from LE on PE
MG symptoms worsen with use but improve with ACHEs
LE symptoms improve with use but not ACHEs
liposarcoma is a proliferation of which cell
Lipoblast
most common site for rhabdomyosarcoma
Vagina of a young girl
Rhabdomyosarcoma is a malignancy of
Rhabdomyoblasts
Rhabdomyosarcoma immunohistochemical stain
Desmin positive
Which bones in fibrous dysplasia
Flat bones (skull, face, ribs)
3 stages of osteitis deformans
Lytic - Osteoclasts go crazy Mixed - Osteoclasts start burning out, osteoblasts wake up Sclerotic - osteoblasts go crazy
Tumors that metastasize to bone
Breast > Prostate > Lung > Thyroid > Kidney > Testicular
Tumor in the diaphysis/medulla of a small bone (metatarsal, metacarpal)
Chondroma
A 25-year-old man presents with lower back pain and a diastolic murmur at the right 2nd intercostal space. Diagnosis?
Ankylosing Spondyitis
why does alcohol precipitate gout attacks?
EtOH competes for the same excretion sites in the kidney as uric acid, leading to a build up of uric acid in the blood
Other name- anti-Jo 1 Ab
histidyl tRNA synthase
A two-month-old male infant was referred to the department of pediatric gastroenterology because of hepatosplenomegaly and thrombocytopenia. Past medical history of the patient revealed that he was hospitalized in the first day of his life in the neonatal unit because of poor feeding and onset of sepsis workup was done. X-ray shows thickened bone and decreased marrow cavities of various bones. Diagnosis?
osteopetrosis
