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136 Cards in this Set
- Front
- Back
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Impaired cartilage proliferation in the growth plate |
Achondroplasia - common cause of Dwarfism - mental function, life span, and fertility are not affected |
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Achondroplasia cause |
Activating mutation in Fibroblast growth factor receptor 3 - autosomal dominant - Overexpression of FGF-A3 inhibits growth - most mutations are sporadic and related to paternal age |
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Clinical features of Achondroplasia |
Short extremities with normal sized head and chest due to poor endochondral bone formation; intramembranous bone formation is not effected |
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Endochondrial bone formation is characterized by |
formation of a cartilage matrix - replaced by bone - mechanism by which long bones grow |
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Intramembranous bone formation is characterized by |
Formation of bone without pre-existing cartilage matrix - mechanism by which flat bones develop |
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Congenital defect of bone resoprtion resulting in structurally weak bone |
Oteogenesis imperfecta - autosomal dominant defect in collagen type I synthesis |
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Osteogenesis Imperfecta Clinical features |
- Multiple fractures of bone (can mimic child abuse, but bruising is absent) - BLUE SCLERA - thinning of scleral collagen reveals underlying choroidal veins - Hearing loss - bones of the middle ear easily fracture |
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Inherited defect of bone resorption resulting in abnormally thick, heavy bone that fractures easily |
Osteopetrosis - due to poor osteoclast function |
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Causes of Osteopetrosis |
Multiple genetic variants exist - Carbonic anhydrase II mutation leads to loss of acidic microenvironment required for bone resoprtion |
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Clinical features of Osteopetrosis |
- Bone fractures - Anemia, thrombocytopenia and leukopenia w/ extramedullary hematopoesis due to bony replacement of the marrow (myeloohthisic process) - Vision and hearing impairment due to impingement on cranial nerves - Hydrocephalus due to narrowing of foramen magnum - Renal tubular acidosis seen w/ carbonic anhydrase II mutation leading to decreased tubular reabsorption of HCO3 = acidosis |
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Tx of Osteopetrosis |
Bone marrow transplant - osteoclasts are derived from monocytes |
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Defective mineralization of osteoid |
Rickets/Osteomalacia - Osteoblasts normally produce osteoid which is then mineralized w/ calcium/phosphate to form bone |
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Causes of Rickets |
Low levels of Vitamin D that results in low serum calcium and phosphate |
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Vitamin D is normally derived from |
Skin exposure to sunlight (85%) and from the diet 15% |
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Activation of Vitamin D requires |
25 hydroxylation by the liver followed by 1 hydroxylation by the PCT |
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Active Vitamin D raises serum Calcium and phosphate by acting on |
Intestine - increases absorption of Calcium and phosphate Kidney - increases reabsorption of calcium and phosphate Bone - increases resorption of Ca/P |
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Vitamin D deficiency is seen with |
- decreased sun exposure - poor diet - malabsorption - liver failure - renal failure |
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Rickets is due to low vitamin D in |
Children - results in abnormal bone mineralization |
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Rickets commonly arises in children less than |
less than 1 year of age |
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Rickets presents with |
Pigeon breast deformity - inward bending of the ribs w/ anterior protrusion of sternum Frontal bossing - enlarged forehead - due to osteoid deposition on the skull Rachitic Rosary - due to osteoid deposition at the costochondral junction Bowing of the legs may be seen in ambulating children |
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Osteomalacia is due to low Vitamin D levels in |
Adults - Inadequate mineralization results in weak bone with an increased risk of fracture |
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Lab findings in Osteomalacia |
- Increased serum calcium, serum phosphate, PTH, and Alkaline phosphatase |
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Reduction in trabecular bone mass |
Osteoporosis - results in porous bone with an increased risk for fracture |
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Osteoporosis risks |
Based on peak bone mass and rate of bone mass loss thereafter - Peak bone mass reached by 30 years of age - Based on genetics (Vit D variants), diet, exercise Thereafter, slightly less than 1% of bone mass is lost each year - bone loss more accelerated w/ lack of weight bearing exercises, poor diet, decreased estrogen |
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Most common forms of osteoporosis |
Senile and post-menopausal |
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Clinical features of Osteoporosis |
Bone pain and fractures in weight bearing areas such as vertebrae (leads to loss of height and kyphosis), hip, and distal radius
Bone density is measured using a DEXA scan Serum calcium, Phosphate, PTH, and alkaline phosphatase are normal - labs help to exclude osteomalacia |
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Tx of Osteoporosis |
Exercise, vitamin D, and calcium - limit bone loss Bisphosphoantes - induce apoptosis of osteoclasts ERT is debated Glucocorticoids are contraindicated - worsens osteoporosis |
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Imbalance between osteoclast and osteoblast function usually seen in late adulthood |
Paget disease of bone - etiology unknown, may be viral - localized process involving one or more bones, does not involve entire skeleton |
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Three distinct phases of Paget Disease |
1) osteoclastic 2) mixed osteoblastic-osteoclastic 3) osteoblastic End result is thick, sclerotic bone that fractures easily - Biopsy reveals a mosaic pattern of lamellar bone |
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Clinical features of Paget Disease |
1) Bone pain due to microfratures 2) Increasing hat size - skull is affected 3) Hearing loss - impairment on cranial nerve 4) Lion like facies - involvement of craniofacial bones 5) Isolated elevated alkaline phosphatase - most common cause of isolated elevated alkaline phosphate in patients over 40 |
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Treatment of Pagets Disease |
Calcitonin - inhibits osteoclast function Bisphosphonates - induce apoptosis of osteoclasts |
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Complications of Paget Disease |
High output cardiac failure - due to formation of AV shunts in bone Osteosarcoma |
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Infection of marrow and bone |
Osteomyelitis - usually occurs in children - most commonly bacterial, arises via hematogenous spread |
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Transient bacteria in children leads to seeding of |
metaphysis |
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Open wound bacteremia in adults leads to seeding of |
Epiphysis |
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Causes of osteomyelitis |
- Staph aureus (most common 90%) - Gonorrheae (STD) - Salmonella - sickle cell disease - Pseudomonas - IV drug users/diabetics - Pasteurella - cat/dog scratches/bites - Mycobacterium TB - Pott's disease |
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Clinical features of Osteomyelitis |
Bone pain w/ systemic signs of infection including fever and leukocytosis Lytic focus (abscess) surrounded by sclerosis of bone on X-ray - lytic focus is called sequestrum - Sclerosis is called involuvrum |
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Lytic focus in osteomyelitis |
Sequestrum |
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Sclerosis in osteomyelitis |
Involucrum |
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Diagnosis of osteomyelitis |
Blood culture |
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Ischemic necrosis of bone and bone marrow |
Avascular/Aseptic necrosis |
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Causes of avascular necrosis |
Trauma/fracture (most common) Steroids Sickle cell anemia Caisson disease |
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Major complications of avascular aseptic necrosis |
Osteoarthritis and fractures
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Benign tumor of bone |
Osteoma |
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Osteomas commonly arise in |
Surface of facial bones |
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Osteoma is associated with |
Gardner syndrome |
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Benign tumor of osteoblasts surrounded by a rim of reactive bone |
Osteoid Osteoma - Occurs in young adults less than 25 |
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Osteoid osteoma arises in |
Cortex of long bones |
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Osteoid osteoma presents as |
bone pain that resolves with aspirin Imaging reveals a bony mass (<2 cm) with a radioluscent core (osteoid) |
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Osteoblastoma is similar to osteoid osteoma but it |
Larger ( > 2 cm), arises invertebrae, and presents as bone pain that does not respond to aspirin |
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Tumor of bone with an overlying cartilage cap that is the most common benign tumor of bone |
Osteochondroma |
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Osteochondroma arises from |
Lateral projection of the growth plate (metaphysis) Bone is continuous with the marrow space Overlying cartilage can transform (rarely) to chondrosarcoma |
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Malignant proliferation of osteoblasts |
Osteosarcoma |
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Peak incidence of osteosarcoma |
Teenagers Less commonly seen in elderly |
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Risk factors for osteosarcoma |
Familial retinoblastoma, Paget disease, Radiation exposure |
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Osteosarcoma normally arises in |
Metaphysis of long bones, usually the distal femur or proximal tibia |
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Osteosarcoma presents as |
Pathologic fracture or bone pain with swelling Imaging reveals a destructive mass with sunburst appearance and lifting periosteum Biopsy reveals pleomorphic cells that produce osteoid |
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Destructive mass w/ sunburst appearance and lifting of periosteum in osteosarcoma |
Codman triangle |
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Tumor comprised of multinucleated giant cells and stromal cells occurring in young adults |
Giant cell tumor - locally aggressive tumor, may recur |
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Giant cell tumor arises in |
Epiphysis of long bones, usually the distal femur or proximal tibia |
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Giant cell tumor appears as _____________ on x-ray |
Soap bubble |
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Malignant proliferation of poorly differentiated cells derived from neuroectoderm |
Ewing Sarcoma |
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Ewing sarcoma arises in |
Diaphysis of long bones - usually in male children < 15 |
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Ewing sarcoma appearance on X-ray |
Onion skin |
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Ewing Sarcoma biopsy reveals |
Small, round blue cells that resemble lymphocytes - Can be confused w/ lymphoma or chronic osteomyelitis - (11;22) translocation is characteristic |
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Ewing Sarcoma often presents with |
metastasis, responsive to chemotherapy |
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Benign tumor of cartilage |
Chondroma - usually arises in the medulla of small bones in the hands and feet |
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Malignant cartilage forming tumor |
Chondrosarcoma - Arises in the medulla of the pelvis or central skeleton |
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Metastatic tumors of bone are ___________ common than primary tumors |
MORE common - usually result in lytic/punched out lesions |
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Prostatic carcinoma classically produces |
Osteoblastic lesions |
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Basic Principles of Joints |
- Connection between two bones - Solid joints are tightly connected to provide structural strength Synovial joints have a joint space to allow for motion - articular surface of adjoining bones is made of hyaline cartilage (type II collagen) that is surrounded by a joint capsule - synovium lining the joint capsule secretes fluid rich in hyaluronic acid to lubricate the joint and facilitate smooth motion |
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Progressive degeneration of articular cartilage (most common) |
Osteoarthritis - most often due to wear and tear |
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Major risk factor of osteoarthritis |
Age > 60 Obesity Trauma |
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Joints affected by osteoarthritis (oligoarticular) |
- hips - lower lumbar spine - knees - distal interphalangeal joints - proximal interphalangeal joints of fingers |
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Classic presentation of osteoarthritis |
Joint stiffness in the morning that worsens during the day |
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Pathologic features of osteoarthritis |
- disruption of the cartilage that lines the articular surface - fragments of cartilage floating in the joint space - Eburnation of subchondral bone - Osteophyte formation (reactive bony outgrowths) |
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Fragments of cartilage floating in the joint space |
Joint mice |
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Reactive bony outgrowths |
Osteophyte formation |
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Osteophyte formation arising in the DIP |
Heberden nodes |
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Osteophyte formation arising in PIP joints of fingers |
Bouchard nodes |
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Chronic systemic auto immune disease |
Rheumatoid arthritis |
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Rheumatoid arthritis classically arises in |
Women of late childhood bearing age |
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HLA associated with RA |
HLA-DR4 |
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Hallmark of RA |
Synovitis leading to formation of pannus - inflamed granulation tissue - leads to destruction of cartilage and ankylosis (fusion) of the joint |
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Clinical features of RA |
Arthritis w/ morning stiffness that improves with activity - symmetric involvement of PIP joints of fingers, wrists, elbows, ankles, and knees - DIP is spared Fever, malaise, weight loss, myalgias Rhematoid nodules Vasculitis Baker Cyst Pleural effusions, lymphadenopathy, Interstitial lung fibrosis |
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Central zone of necrosis surrounded by epitheloid histiocytes, arise in skin and visceral organs |
Rheumatoid nodules |
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Swelling of bursa behind the knee in RA |
Bakers cyst |
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Symmetric involvement of PIP joints in RA |
Swan neck deformity |
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Deviation of wrists in RA |
Ulnar deviation |
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Lab Findings in RA |
- IgM auto-antibody against Fc protion of IgG (Rheumatic factor), marker of tissue damage and disease activity - Neutrophils and high protein in synovial fluid |
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Complications of RA |
Anemia of chronic disease and secondary amyloidosis |
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Seronegative spondyloarthropathies are associated with |
- Lack of Rheumatoid factor - Axial skeletal involvement - HLA-B27 association |
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Ankylosing Spondylarthritis involves the |
Sacroiliac joints and spine |
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Ankylosing spondylarthritis presents as |
Low back pain, involvement of vertebral bodies eventually arises, leading to fusion of the vertebrae in young adult males Extra-articular manifestations include uveitis and aortitis (leading to aortic regurgitation) |
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Fusion of the vertebrae in Ankylosing spondylarthritis |
Bamboo spine |
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Characterized by a triad of arthritis, urethritis, and conjunctivitis |
Reiter Syndrome - arises in young adults (usually males) weeks after a GI or Chlamydia trachomatis infection |
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Psoriatic arhtritis is seen in 10% of cases of psoriasis |
Involves axial ad peripheral joints - DIP joints of the hands and feet are most commonly affected - Leading to SAUSAGE finger and toes |
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Arthritis due to an infectious agent usually bacterial |
Infectious arthritis |
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Causes of infectious arthritis |
N gonorrheae - young adult, most common cause S aureus - older children and adults |
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Most common joint affected in infectious arthritis |
Knee |
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Infectious arthritis presentation |
Warm joint with limited ROM - fever - increased WBC - elevated ESR |
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Deposition of monosodium urate crystals in tissues, especially the joints |
Gout - due to hyperuricemia, related to overproduction or decreased excretion of uric acid - uric acid derived from purine metabolism and is excreted by the kidney |
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____________ gout is the most common form |
Primary gout - etiology unknown |
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Secondary gout is seen with |
Leukemia and myeloproliferative disorders - increased cell turnover leads to hyperuricemia Lesch-Nyhan syndrome - X linked deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPGRT) Renal insufficiency - decreased renal excretion of uric acid |
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Lesch-Nyhan syndrome presents as |
Mental retardation and self-mutilation |
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Gout presents as |
Exquisitely painful arthritis in the great toe (podagra) - MSU crystals deposit in the joint, triggering an acute inflammatory reaction - Alcohol or consumption of meat may precipitate arthritis |
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Chronic gout leads to |
Development of tophi - white chalky aggregates of uric acid crystals w/ fibrosis and giant cell reaction in soft tissue and joints Renal failure - Urate crystals may deposit in kidney tubules (urate nephropathy) |
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Lab findings in gout |
- hyperuricemia - synovial fluid shows needle shaped crystals w/ NEGATIVE birefringence under polarized light |
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Pseudogout resembles gout clinically but is due to |
Deposition of calcium pyrophosphate dihydrate - synovial fluid shows rhomboid shaped crystals w/ weakly positive birefringence under polarized light |
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Inflammatory disorder of the skin and skeletal muscle |
Dermatomyositis - unknown etiology - gastric carcioma might be a factor |
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Clinical features of Dermatomyositis |
- Bilateral muscle weakness (distal late in disease) - Red rash of upper eyelids , malar rash - Red papules on elbows, knuckles, and knees |
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Red papules on elbows, knees, and knuckles |
Grotton lesion |
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Lab findings in Dermatomyositis |
- Increased creatine kinase - positive ANA and anti-Jo-1 antibody - Perimysial inflammation (CD4 T cells) w/ Perifascicular atrophy on biopsy |
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Tx of dermatomyositis |
Corticosteroids |
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Inflammatory disorder of skeletal muscle |
Polymyositis - resembles dermatomyositis but skin is NOT involved - ENDOMYSIAL inflammation (CD8 T cells) with necrotic muscle fibers is seen on biopsy |
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Degenerative disorder characterized by muscle wasting and replacement of skeletal muscle with adipose tissue |
X linked muscular dystrophy |
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X linked muscular dystrophy caused by |
Mutations in dystrophin gene - Important for anchoring muscle cytoskeleton to the ECM - Mutations are often spontaneous, large gene size predisposes to high rate of mutation |
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Duchene muscular dystrophy is due to a _____________ |
deletion of dystrophin |
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Duchenne muscular dystrophy presents as |
Proximal muscle weakness at 1 year of age, progresses to distal muscles - Calf pseudohypertrophy - Serum creatine kinase is elevated |
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Death from Duchenne muscular dystrophy results from |
Cardiac or respiratory failure - myocardium is commonly involved |
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Becker muscular dystrophy is due to |
mutated dystrophin gene - usually results in milder disease |
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Antibodies against post-synaptic Ach receptor at NMJ more commonly seen in women |
Myasthenia gravis |
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Clinical features of Myasthenia gravis |
- Muscle weakness that worsens with use and improves with rest
- Classically involves the eyes leading to ptosis and diplopia - Symptoms improve with AchE agents - Associated w/ Thymic hyperplasia or thymoma, thymectomy improves symptoms |
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Antibodies against presynaptic Ca channels of the NMJ arising as a paraneoplastic syndrome due to small cell lung carcinoma |
Lambert Eaton Syndrome |
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Lambert Eaton leads to |
impaired Ach release - Firing of presynaptic Ca channels is required for Ach release |
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Clinical features of Lambert Eaton syndrome |
- Proximal muscle weakness that IMPROVES with use - eyes are usually spared - AchE agents DO NOT improve symptoms - Resolves with resolution of cancer |
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Benign tumor of adipose tissue |
Lipoma - Most common benign soft tissue tumor in adults |
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Malignant tumor of adipose tissue |
Liposarcoma |
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Most common malignant soft tissue tumor in adults |
Liposarcoma |
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Characteristic cells of liposarcoma |
Lipoblasts |
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Benign tumor of skeletal muscle |
Rhabdomyoma - Cardiac rhabdo is associated with tuberous sclerosis |
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Malignant tumor of skeletal muscle |
Rhabdomyosarcoma |
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Most common malignant soft tissue in children |
Rhabdomyosarcoma |
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Characteristic cell of Rhabdomyoma |
Rhabdomyoblast |
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Marker in Rhabdomyoma |
Desmin positive |
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Most common site of Rhabdomyosarcoma |
Head and neck Vagina - classic site in young girls |
