Pathoma 3. Flashcards
achondroplasia
impaired cartilage proliferation in the growth plate; common cause of dwarfism
What causes achondroplasia?
AD activating mutation in fibroblast growth factor receptor 3 (FGFR3) - overexpression INHIBITS growth
What are clinical features of achondroplasia?
short extremities with normal sized head and chest (due to poor endochondral bone formation, but normal intramembranous bone formation)
Endochondral bone formation
formation of a cartilage matrix which is then replaced with bone (long bones)
Intramembranous bone formation
formation of bone without a preexisiting cartilage matrix
Osteogenesis imperfecta
congenital defect of bone formation resulting in structurally weak bone
What causes osteogenesis imperfecta?
AD defect in collagen type I synthesis
What are the clinical features of osteogenesis imperfecta?
multiple fractures of bone, blue sclera, hearing loss
Osteopetrosis
inherited defect of bone resorption resulting in abnormally thick, heavy bone that fractures easily (like chalk)
What is osteopetrosis the result of?
poor osteoclast function due to carbonic anhydrase II mutation (leads to loss of the acidic microenvironment required for bone resorption)
What are the clinical features of osteopetrosis?
bone fractures, anemia, thrombocytopenia, leukopenia with extra medullary hematopoiesis (due to bony replacement of the marrow), vision and hearing impairment, hydrocephalus (narrowing of foramen magnum), renal tubular acidosis (carbonic anhydrase II mutation)
What is the treatment for osteopetrosis?
bone marrow transplant because osteoclasts are derived from monocytes (need new monocytes)
Rickets/Osteomalacia
defective mineralization of osteoid (normally produced by osteoblasts)
What causes rickets/osteomalacia?
low levels of Vit D (causes low serum calcium and phosphate)
How is vit D activated?
by 25-hydroxylation by the liver followed by 1-alpha-hydroxylation by the proximal tubule cells of the kidney
How does active Vit D raise serum calcium and phosphate?
intestine (increase absorption), kidney (increase resorption), bone (increase resorption)
What can vit D deficiency be caused by?
decreased sun exposure, poor diet, malabsorption, liver failure, renal failure
How does rickets present?
in children - pigeon breast deformity (inward bending of the ribs), frontal bossing (enlarged forehead), rachitic rosary (osteoid deposition at the costochondral junction), bowing of legs
How does osteomalacia present?
in adults - inadequate mineralization = weak bone, decreased serum calcium, decreased serum phosphate (because low vit D), increased PTH (because low Ca2+), increased alkaline phosphatase
What is osteoporosis?
reduction in trabecular bone mass resulting in porous bone with an increased risk for fracture
What are the risk factors of osteoporosis?
peak bone mass (age 30) and rate of bone loss afterwards. based on weight bearing exercise, poor diet, decreased estrogen
What are the most common forms of osteoporosis?
senile and postmenopausal
How does osteoporosis present clinically?
bone pain and fractures in weight-bearing area, bone density on DEXA scan, serum calcium, phosphate, PTH, alkaline phosphatase are NORMAL
What presents clinically like osteoporosis? How are they distinguished?
osteomalacia - labs are normal in osteoporosis for calcium, phosphate, PTH, alkaline phosphatase
What is the treatment for osteoporosis?
exercise, vit D, calcium to limit bone loss, bisphosphonates to induce apoptosis of osteoclasts
What drug is contraindicated in osteoporosis?
glucocorticoids because they worsen osteoporosis
Paget disease of bone
imbalance between osteoclast and osteoblast function
What is the etiology of page disease of bone?
unknown, but maybe viral
Where is paget disease of bone typically localized to?
one or more bones, but does NOT involve entire skeleton
What are the three stages of page disease of bone?
- osteoclastic (start working without permission of osteoblasts (osteoblasts receive signal from PTH) 2. mixed osteoblastic-osteoclastic (osteoblasts lays down as quickly as possible to try and make up for out of control osteoclasts but makes weak bone) 3. osteoblastic
What does biopsy of paget disease of bone reveal?
mosaic pattern of lamellar bone
What are the clinical features of paget disease of bone?
bone pain, increasing hat size, hearing loss, lion-like facies, isolated elevated alkaline phosphatase
What is treatment for paget disease of bone?
calcitonin (inhibits osteoclast function - opposite of PTH) and bisphosphonates (induces apoptosis of osteoclasts)
Bisphosphonates in clinical treatment
induce apoptosis of osteoclasts
What are complications of paget disease of bone?
high-output cardiac failure (due to AV shunts in bone) and osteosarcoma
Osteomyelitis
infection of marrow and bone typically in children
What is cause of osteomyelitis?
bacterial via hematogenous spread
Where does osteomyelitis seed in children?
transient bacteremia seeds metaphysis (growth plate)
Where does osteomyelitis seed in adults?
open-wound bacteremia seeds epiphysis (rounded end of a long bone)
What are common causes of osteomyelitis?
staph aureus (most common), gonorrhoeae, salmonella, pseudomonas, pasteurella, mycobacterium tuberculosis
What are clinical features of osteomyelitis?
bone pain with systemic signs of infection (fever and leukocytosis), lytic focus (abscess) surround by sclerosis of bone on x-ray (sclerosis surrounding necrosis)
How is diagnosis of osteomyelitis made?
blood culture
What is avascular necrosis?
ischemic necrosis of bone and bone marrow
What are causes of avascular necrosis?
trauma or fracture (most common), steroids, sickle cell, caisson disease (gas emboli lodging in bone)
What are complications of avascular necrosis?
osteoathritis and fracture
Osteoma - what is it and where does it typically present?
benign tumor of bone - surface of facial bones
Osteoid Osteoma
benign tumor of osteoblasts surrounded by a rim of reactive bone
Who doe osteoid osteoma typically occur in?
young adults (
Where does osteoid osteoma typically present?
cortex of long bones (outside - usually diaphysis)
How does osteoid osteoma typically present?
bone pain that RESOLVES WITH ASPIRIN
How does osteoid osteoma present on imaging?
bony mass with a radiolucent core
What is an osteoblastoma?
similar to osteoid osteoma but is larger, arises in vertebrae, and presents as bone pain that DOES NOT RESOLVE WITH ASPIRIN
Osteochondroma
tumor of bone with an overlying cartilage cap; most common benign tumor of bone
Where does osteochondroma arise?
from lateral projection of the growth plat (metaphysis) - bone is continuous with the marrow space
What is a complication of osteochondroma?
overlying cartilage can transform to chondroscarcoma
Osteosarcoma
malignant proliferation of osteoblasts
When is the peak incidence of osteosarcoma?
teenagers, less commonly in elderly (risk factors familial retinoblastoma, paget disease, radiation exposure)
How does osteosarcoma present?
pathologic fracture or bone pain with swelling
How does osteosarcoma present on imaging?
a destructive mass with a “sunburst” appearance and lifting of the periosteum
What does biopsy of osteosarcoma reveal?
pleomorphic cells that produce osteoid
Giant cell tumor
tumor comprised of multinucleate giant cells and stromal cells occurring in young adults
Where does a giant cell tumor airse?
epiphysis of long bones, usually distal femur or proximal tibia
How does a giant cell tumor appear on x-ray?
soap-bubble
Ewing sarcoma
malignant proliferation of poorly-differentiated cells derived from neuroectoderm
Where does ewing sarcoma arise?
diaphysis of long bones, usually male children
How does ewing sarcoma appear on x-ray?
onion-skin appearance
What does biopsy of ewing sarcoma reveal? What is characteristic of ewing sarcoma?
small, round blue cells that resemble lymphocytes and have an 11;22 characteristic translocation
Condroma
benign tumor of cartilage that usually arises in the medulla of small bones
Chondrosarcoma
malignant cartilage-forming tumor that arises in medullar of pelvis/central skeleton
Metastatic tumors in bones
more common than primary tumors - usually result in osteolytic (punched-out) lesions
What is the exception of metastatic tumors resulting in osteolytic lesions?
prostatic carcinoma (classically produces osteoblastic lesions)
What type of cartilage is present in synovial joints?
type II collagen - hyaline cartilage
What is the synovium lining the join capsule secrete?
fluid rich in hyaluronic acid
Osteoarthritis
degenerative joint disease - progressive degeneration of articular cartilage
What is the most common cause of osteoarthritis?
wear and tear
What are the risk factors for osteoarthritis?
age, obesity, trauma
What are the most common joints osteoarthritis affects?
hips, lower lumbar spine, knees, DIP, PIP
What is the classic presentation of osteoarthritis?
joint stiffness in the morning that worsens during the day
What are pathologic features of osteoarthritis?
- disruption of the cartilage that lines the articular surface; fragments of cartilage floating in the joint space “joint mice” 2. eburnation of the subchondral bone 3. osteophyte formation (reactibe bony outgrowths DIP and PIP joints)
Rheumatoid arthritis
chronic, systemic autoimmune disease
What is rheumatoid arthritis associated with?
HLA-DR4
What is the hallmark of rheumatoid arthritis?
synovitis leading to formation of a pannus (inflamed granulation tissue)
What does rheumatoid arthritis lead to?
destruction of cartilage and ankylosis (fusion) of the joint
What are the clinical features of rheumatoid arthritis?
- morning stiffness that improves with activity. symmetric involvement of PIP, wrists, elbows, ankles, and knees; DIP spared 2. fever malaise, weight loss, myalgia 3. rheumatoid nodules 4. vasculitis 5. baker cyst 6. pleural effusions, lymphadenopathy, interstitial lung fibrosis
What is seen on x-ray of rheumatoid arthritis?
joint-space narrowing, loss of cartilage, osteopenia
What are lab findings for rheumatoid arthritis?
IgM autoantibody against Fc portion of IgG (rheumatoid factor); also neutrophils and high protein in synovial fluid
What are complications of rheumatoid arthritis?
anemia of chronic disease and secondary amyloidosis
Seronegative spondyloarthropathies?
group of joint disorders characterized by 1. lack of rheumatoid factor (serum - ); 2. axial skeleton involvement; 3. HLA-B27 association
What does ankylosing spondyloarthritis involve?
sacroiliac joints and spine (presents with low back pain and eventually leads to fusion of vertebrae)
Who is at greatest risk to developing ankylosing spondyloarthritis?
young adults most often male
What are extra-articular manifestations of ankylosing spondyloarthritis?
uveitis and aortitis
What is Reiter syndrome?
a seronegative spondyloarthropathy; characterized by triad of arthritis, urethritis, and conjunctivitis usually in young males after GI of chlamydia infection
What is psoriatic arthritis?
involves axial and peripheral joints - DIP joints most ofter leading to sausage fingers/toes - in 10% of cases of psoriasis
Infectious arthritis
usually bacterial - n gonorrhoeae (most common) and staph aureus
What is classically seen in infectious arthritis?
single joint, usually knee
How does infectious arthritis present?
warm joint with limited range of motion, fever, increased WBC count, elevated ESR
Gout
deposition of monosodium urate (MSU) crystals in tissue, especially joints
What is gout due to?
hyperuricemia; related to overproduction or decreased excretion of uric acid (which is derived from purine metabolism and excreted by kidney)
What is the most common form of gout?
primary gout
What is secondary gout seen with?
- leukemia and myeloproliferative disorders (increased cell turnover leads to hyperuricemia) 2. Lesch-Nyhan syndrome (HGPRT deficiency presenting with mental retardation and self mutilation) 3. renal insufficiency
How does acute gout present?
painful arthritis of the great toe - MSU crystal deposit causing acute inflammatory reaction
What may precipitate arthritis causing acute gout?
alcohol (alcohol is in competent for excretion with uric acid) or consumption of meat (bringing in lots of DNA/RNA)
What does chronic gout lead to?
- development of top - white, chalky aggregates of uric acid crystals with fibrosis and giant cell reaction in the soft tissue and joints. 2. renal failure (crystals deposit in kidney tubules)
What are lab findings in gout?
hyperuricemia; synovial fluid shows needle-shaped crystals with negative birefringence on polarized light
What is pseudogout?
due to deposition of calcium pyrophosphate dehydrate (CPPD); synovial fluid shows rhomboid shaped crystals with weakly positive birefringence
Dermatomyositis
inflammatory disorder of skin and skeletal muscle - sometimes associated with carcinoma
What are clinical features of dermatomyositis?
bilateral proximal muscle weakness (can’t comb hair or climb stairs), rash of upper eyelids, malar rash, red papules on elbows, knuckles, knees
What can be confused as lupus?
dermatomyositis (malar rash)
What are lab findings in dermatomyositis?
increased creatine kinase (muscle), positive ANA and anti-Jo-1 antibody, perimysial inflammation with perifasicular atrophy on biopsy (edge of muscle - close to skin)
What is treatment for dermatomyositis?
corticosteroids
Polymyositis
inflammatory disorder of skeletal muscle - no skin involve; endomysial (inside muscle)
How does biopsy of polymyositis differ from dermatomyositis?
polymyositis: CD8+ cells (CD4 for dm) with necrotic muscle fibers (perifascicular atrophy for dm)
X-linked muscular dystrophy
degenerative disorder characterized by muscle wasting and replacement of skeletal muscle by adipose tissue
What is X-linked muscular dystrophy due to?
defects of dystrophin gene
What does the dystrophin gene do?
important for anchoring the muscle cytoskeleton to ECM
What is the difference between Duchenne muscular dystrophy and Becker muscular dystrophy?
Duchenne = deletion of dystrophin, Becker = mutated (clinically milder)
How does Duchenne muscular dystrophy present?
presents as proximal muscle weakness at 1 year of age and progresses to distal muscles (calf pseudohypertrophy)
What lab value is elevated in muscular dystrophy?
creatine kinase
What does death usually result from in patients with Duchenne muscular dystrophy?
cardiac or respiratory failure. myocardium commonly involved
lipoma
benign tumor of adipose tissue; most common benign soft tissue tumor
liposarcoma
malignant tumor of adipose tissue; most common malignant soft tissue tumor
What is the characteristic cell in liposarcoma?
lipoblas
Rhabdomyoma
benign tumor of skeletal muscle
What is cardiac rhabdomyoma associated with?
tuberous sclerosis
Rhabdomyosarcoma
malignant tumor of skeletal muscle; most common soft tissue tumor in CHILDREN
What is the characteristic cell of rhabdomyosarcoma? What does it stain for?
rhabdomyoblast; desmin postive
What is the most common site for rhabdomyosarcoma?
head and neck; vagina classic site in young girls
