Quiz 4, Skeletal Flashcards
What is defective in osteogenesis imperfecta?
There is a genetic deficiency of normal type-1 collagen which forms bone matrix
What is Legg-Calve-Perthes syndrome characterized by?
Idiopathic avascular osteonecrosis of the epiphysis of the femoral head leading to an interruption of the blood supply of the head of the femur close to the hip.
What are two causes of Rickets?
Predominantly, a vitamin D deficiency.
Also, dietary calcium deficiency.
What term is used for the condition similar to Rickets in adults?
Osteomalacia
What deformity do toddlers with Rickets typically develop?
Genu varum (bowed legs)
What deformity to older children with Rickets typically develop?
Genu valgum (knock-knees)
What is the term used for patients with Rickets who develop prominent knobs of bone at the costochondral joints?
Rachitic rosary (beading of the ribs)
What conditions can cause osteoporosis?
Malabsorption disorders
hyperthyroidism
hyperparathyroidism
(generalized loss of bone)
Differentiate primary vs. secondary osteoporosis.
Primary = osteopenia from age/menopause Secondary = other medical conditions
What is largely responsible for the increased osteoclast activity in osteoporosis?
Increased levels of cytokines
IL-1, IL-6, TNF-alpha
What are some risk factors for osteoporosis?
Female Low body mass Age Fmhx Hx of fractures after age 50 Low bone mass Hx of fracture in 1st degree relative Estrogen deficiency Amenorrhea Low testosterone (men) Anorexia nervosa Low lifetime calcium intake Vit. D deficiency Inactive lifestyle Smoking ETOH Caucasian/Asian Medications
What postural change is commonly seen in patients with osteoporosis, due to compression fractures of vertebrae?
Kyphosis
What’s the other name for Paget’s disease of bone?
Osteitis deformans
What is Paget’s characterized by?
High bone turnover with accelerated osteoclast and osteoblast activity.
What lab marker is elevated in Paget’s?
Serum alkaline phosphatase
What is the histological hallmark of Paget’s?
MOSAIC pattern of LAMELLAR bone which likened in appearance to a jigsaw puzzle
Unlike osteoPETROSIS which presents at birth, when does Paget’s develop?
4th decade
What is the x-ray appearance of a patient’s skull who has Paget’s?
Area of sclerotic bone and areas of lucency (cotton ball appearance)
What is the first warning sign of Paget’s?
Pain in or over the area of affected bone or a pathologic fracture. Involved area can feel warm.
Does Paget’s affect one bone or multiple?
Either, multiple is more common
How do bones affected by Paget’s typically break?
Linear fracture (straight across)
What is a rare inherited disorder whereby the bones harden and become more dense?
Osteopetrosis
What is a rare inherited bone disease characterized by reduced or dysregulated activity of osteoclasts, resulting in generalized osteosclerosis.
Malignant infantile osteopetrosis (MIOP)
What organism is most commonly isolated from all forms of osteomyelitis?
Staphylococcus aureus
With osteomyelitis, which bones are usually affected in children vs. adults?
Children - long bones
Adults - vertebrae and pelvis
What is the second most common organism causing osteomyelitis in the vertebrae, which used to have its own name (Pott’s Disease)?
Tuberculosis
What is the most common cause of osteomyelitis in adults? (not the organism)
Injury that exposes the bone to local infections
What term describes all of the skeletal changes of chronic renal disease?
Renal osteodystrophy
A fracture that has no associated soft tissue injury is called what?
Closed or Simple (Open or Compound if there is soft tissue injury)
What kind of fracture does the bone not align?
Displaced
What term describes a fracture when the bone is splintered or crushed?
Comminuted
What do you call a fracture occurring in bone already altered by a disease process?
Pathologic fracture
What is a slowly developing fracture that follows a period of increased physical activity?
Stress fracture
Where do solitary bone cysts predominantly occur?
The distal ends of long bones such as the humerus and femur
What does an x-ray of a solitary bone cyst reveal?
Smooth thin cortex in close proximity to the epiphysis
Symmetrical appearance
Bone diameter may be increased at site of cyst
The cavity is filled with clear or bloody fluid
Where are aneurysmal bone cysts most common?
The metaphysis of long bones and also vertebrae
What does an aneurysmal bone cyst look like on x-ray?
Honey-combed appearance
What benign condition involves a bone-forming neoplasm characterized by a small area of neoplastic tissue surrounded by a wide zone of mature, reactive bone?
Osteoid osteoma
Osteoid osteoma are usually solitary. If there are multiple lesions what condition is likely?
Gardner syndrome
What is the x-ray appearance of an osteoid osteoma?
A small, well circumscribed lesion that is round or oval, located near the cortex and surrounded by densely sclerotic bone. May have radiolucent and radiopaque aspects.
What is the gross appearance of an osteoid osteoma?
Area of gritty, cherry red tissue, surrounded by dense sclerotic bone.
What is the primary malignant tumor of bone?
Osteosarcoma
Where do most osteosarcomas occur?
Distal femur or around the knee
Osteosarcomas can occur at any age, but 75% of them happen in what age group?
10-20
What does classic osteosarcoma demonstrate?
Rapid growth and high risk of local spread
“Skip lesions” metastasis within the bone and/or contiguous soft tissues
Pulmonary metastasis is common
What is the microscopic appearance of osteosarcoma?
Atypical cells with large nuclei and small amount of cytoplasm
Osteoid formation
Where are fibrosarcomas usually found?
Knee in either the distal femur and/or proximal tibia
What does a fibrosarcoma produce?
Collagen matrix (not osteoid or chondroid)
What is microscopically characteristic about fibrosarcoma?
Sheets of spindle shaped cells
What condition is usually only present in patients over 20 and is an aggressive tumor composed of oval cells and multinucleated cells that are uniformly distributed throughout the lesion?
Giant cell tumor
What is seen on x-ray of a giant cell tumor?
Destructive radiolucent lesion that is oval shaped and centered in the epiphysis
Causes cortical erosion and thinning which expands the bone contours without a border of new bone formation and sclerosis
What condition is a malignant tumor of bone composed of small, rounded cells that are uniform in size and densely packed? They occur mainly in children.
Ewing sarcoma
What does an x-ray of Ewing sarcoma look like?
Mottled “moth eaten” destructive lesion. Often infiltrates medullary cavity, penetrates the cortex, or extend beyond the bone into surrounding soft tissue
What condition is a malignant disease of monoclonal plasma cell overgrowth in the bone marrow which produces monoclonal immunoglobulin or paraprotein?
Multiple myeloma
What is a common concomitant with multiple myeloma?
Pathological fractures
Bone pain, especially in the back
What is the “ivory vertebra sign”?
Indication of either metastatic cancer or Paget’s disease
What is the most common type of joint disease?
Osteoarthritis
What is osteoarthritis characterized by?
Progressive erosion of articular cartilage
The cellular basis of osteoarthritis can found in what cells?
Chondrocytes
What do chondrocytes produce that inhibits the synthesis of both type 2 collagen and proteoglycans?
Cytokines, including IL-1, IL-6 and TNF-alpha
What does an x-ray of osteoarthritis typically show?
Joint space narrowing
Marginal osteophyte formation
Subchondral bone cysts
Sclerosis
What are Heberden’s nodes and what condition(s) does it occur in?
Joint swelling in the DIPs
Osteoarthritis
What are Bouchard’s nodes and what condition(s) does it occur in?
Joint swelling the PIPs
Osteoarthritis
Fibrous lined cysts in the subchondral bone are a hallmark of what condition?
Osteoarthritis
Bony outgrowths (osteophytes/bone spurs) develop about the margins of joints with what condition?
Osteoarthritis
What is a chronic, systemic inflammatory disease of unknown cause, characterized by polyarthritis which is often progressive and deforming?
Rheumatoid arthritis
What are the extra-articular manifestations of rheumatoid arthritis?
Rheumatoid nodules Arteritis Pericarditis Peripheral neuropathy from nerve entrapment Lymphadenopathy
RA is commonly associated with a group of what autoantibodies?
Anti-IgG autoantibodies called rheumatoid factors
What is RA associated with that is encoded within the major histocompatibility complex?
Class II antigens, such as HLA-DR4
How many joints does RA typically affect and which joints are most common?
3 or more
MCP, PIP, wrist, elbow, knee, ankle, MTP.
What is characteristic of the primary joint lesion in RA?
Occurs in the synovial membrane of affected joints and is called diffuse proliferative and exudative synovitis.
The synovial membrane becomes grossly enlarged, congested, edematous, thickened
What causes deformity and dislocation of misshapen bone ends seen in RA?
Muscular imbalance and contracture along with laxity of the joint capsule and ligaments in joints that are previously distended by effusions
The clinical triad of RA with splenomegaly, and manifestations of hypersplenism, such as leukopenia, is called what?
Felty’s syndrome
What serologic test is used for RA was recently developed?
Anti-citrullinated protein antibodies (ACPAs or anti-CCP)
What conditions are positive for RF positive?
Sjogren’s, SLE, progressive systemic sclerosis, infectious hepatitis, polymyositis/dermatomyositis, syphilis, and tuberculosis
Juvenile rheumatoid arthritis is very similar in children as compared to adults, but what are the noticeable clinical differences?
High fever
Rash
Lymphadenopathy
What family of conditions are seronegative for RF but are characterized by inflammatory involvement of the SI joint, small posterior intervertebral articulations and adjacent soft tissues and are often associated with HLA-B27?
Seronegative spondyloarthropathies
What are the seronegative spondyloarthropathies?
Ankylosing spondylitis Spondyloarthritis Reactive arthritis (Reiter's) Enteropathic arthritis Psoriatic arthritis
What condition is a chronic inflammatory joint disease of the axial spine, especially the SI joint, more common in males, starting in adolescent years?
Ankylosing spondylitis
What x-ray finding is pathognomonic for ankylosing spondylitis?
“Bamboo spine”
What condition is an autoimmune reaction to an infection, typically affecting men in their 20’s/30’s
Reactive arthritis (Reiter’s)
Infections of what type are most commonly implicated in reactive arthritis?
Gastrointestinal or genitourinary in origin. (Chlamydia is MC for GU origin)
What are some common sx of reactive arthritis?
"Sausage toe" Keratoderma blennorrhagicum Joint stiffness synovitis back pain
What condition is similar to reactive arthritis, but occurs following bowel infection?
Enteropathic arthritis
What are the most common affected joints in enteropathic arthritis and how quickly do sxs manifest?
Knees, ankles (sometimes wrists, fingers, toes)
Within days of infection
What is the mechanism of pathology in enteropathic arthritis?
Antibody response to LPS found in cell wall of shigella, salmonella, yersinia, campylobacter.
The organisms themselves do not infect the joints.
Arthritis sx resolve in a year or less usually
What joints are typically affected first with with psoriatic arthritis?
DIPs of fingers and toes
What is a distinctive feature of psoriatic arthritis?
Pitting of the nails
What is onycholysis what is the MC cause of it?
Detachment of the nail from its bed
Psoriasis
What does onycholysis put someone at risk for? If one is found, what should be in your ddx?
Secondary infection (bacterial) Melanoma
T/F: microbial organisms of all types can cause arthritis
True, it’s called infectious or septic arthritis
What organism is the MC and 2nd MC cause of bacterial (suppurative) arthritis?
1st: Staph. aureus
2nd: Streptococci
What organism are sickle cell patients at risk of infection for in their joints?
Salmonella
What organism was the most common cause of bacterial arthritis in children before a vaccine reduced the incidence?
Haemophilus influenzae
What organism resulting in bacterial arthritis is most often seen in young adults that causes migratory arthralgias and has the pathognomonic feature of multiple macules or vesicles seen over the trunk?
Neisseria gonorrhoea
What organism causing bacterial arthritis is commonly seen in the elderly, IV drug users, or the seriously ill?
Escherichia coli
What is a clinical distinctive feature between gonococcal and nongonococcal arthritis?
Gonococcal: Migratory with multiple joints involved, less commonly has a fever
Nongonococcal: Single joint involved, fever, elevated WBC.
What joints are typically most affected by tuberculous arthritis?
Weight bearing joints (Hips > knees > ankles)
T/F: Tuberculosis can affect the axial spine
True, it’s called Pott’s disease (affects thoracic and lumbar most commonly)
What is the species of tick that carries lyme disease?
Ixodes scapularis
What is the microorganism responsible for lyme disease?
Borrelia burgdorferi, a spirochete
What is the first sign of lyme disease and what follows it?
Skin infection, typically followed by joint symptoms within 2 weeks - 2 years.
What is the dominant feature of late lyme disease?
Arthritis (remit and migrate) affecting the knees > ankles > shoulders > elbows.
What is the characteristic rash of lyme disease?
Erythema migrans
What are some viruses that can cause arthritis?
Parvovirus 19
rubella
hepatitis C
HIV
Which crystalline arthritis is due to deposition of monosodium urate? and which is due to deposition of calcium pyrophosphate?
Gout
Pseudogout
What are the lifestyle factors that predispose one toward gout?
Heavy alcohol intake and obesity (and being a man 9:1)
What is the term to describe gout developing as a consequence of ingesting lead contaminated alcohol (moonshine)?
Saturnine gout
Hyperuricemia can result in supersaturation of synovial fluid with urate crystals which precipitate out of solution. What does this result in?
Released crystals are chemotactic to leukocytes and also activate the complement system leading to neutrophils and macrophage accumulation in the joint space.
What is seen in synovial fluid with acute gout using polarized microscopy?
Needle shaped birefringent crystals
The phagocytosis of uric acid crystals by macrophages results in what?
Release of toxic free radicals and leukotrienes. Activated neutrophils also release lysosomal enzymes which are destructive of the joint and synovial membrane
How can gout affect the kidneys?
Crystalline deposition within the medulla of the kidney can lead to gouty nephropathy and potential renal failure
What is the pathognomonic lesion of gout and what is it?
Tophus, masses of crystalline or amorphous urate deposits by inflammatory debris.
Pseudogout (chondrocalcinosis) is due to what?
Intraarticular deposition of calcium pyrophosphate (CCPD) crystals.
What joints are typically affected by CPPD (pseudogout)?
Knee and ankle
What is seen in the synovial fluid of pseudogout with CPPD?
Rhomboidal birefringent crystals
What is a cyst that is usually located near a joint capsule or tendon sheath?
Ganglion
A ganglion arises as a result of what?
Cystic degeneration of connective tissue
T/F: A ganglion cyst lacks a true cell lining causing a communication of with the joint space.
False, It does lack a true cell lining and is filled with synovial-like fluid, but it does not communicate with the joint space.
What is a Baker’s cyst?
Synovial cyst (herniation of synovial fluid through a joint capsule) developing in the popliteal fossa. They are a common complication of RA.
What term is used to describe several closely related benign neoplasms that can develop in the synovial lining of joints, tendon sheaths and bursae?
Villonodular synovitis
What are the two most common types of villonodular synovitis?
Pigmented (PVNS) and diffuse-type giant cell tumor of tendon sheaths (GCTTS)
What is a rare condition that occurs most often about the knee and ankle in young adults, arises close to joints, tendon sheaths and bursae, and x-rays reveal focal calcification?
Synovial sarcoma (malignant synovioma)
What is the term used to describe a broad range of inherited diseases that are characterized by progressive muscle damage and weakness?
Muscular dystrophy
What is the most common and most serious of the muscular dystrophies?
Duchenne’s
What causes Duchenne’s muscular dystrophy?
A defective gene on the X chromosome that leads to an inability to produce one of the proteins in the skeletal muscle cell membrane called dystrophin. Its absence permits excess calcium to penetrate the muscle membrane or sarcolemma.
What does the excess calcium within the muscle membrane in Duchenne’s MD lead to?
Reactive oxygen species eventually leading to necrosis of muscle fibers which are replaced with adipose and fibrotic CT.
What age does Duchenne’s manifest in and what it the survivability?
Severe weakness between 2-6, wheelchair bound by 12, death in late teens early twenties. Almost always in boys.
What is the typical cause of myasthenia gravis?
Circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction, inhibiting its stimulating effect.
What is the hallmark symptom of myasthenia gravis?
Muscle weakness that worsens during periods of activity and improves after periods of rest.
What muscles are especially affected in myasthenia gravis?
Muscles that control the eye and eyelid movement, facial expression, chewing, talking, and swallowing.
What condition is strongly associated with myasthenia gravis?
Thymus abnormalities
Hyperplasia in women
Thymoma in males
What does a muscle biopsy of a patient with myasthenia gravis reveal?
Large collections of lymphocytes and necrotic muscle fibers that appear pale and atrophic
What condition causes progressive muscle weakness, first noticed in the upper legs and upper arms, and is often associated with small cell lung cancer?
Lamber-Eaton syndrome
Lambert-Eaton syndrome involves antibodies directed against what? and what does it cause?
Presynaptic calcium channels in the neuromuscular junction which inhibits the release of acetylcholine.
What will patient’s with Lambert-Eaton syndrome exhibit in regards to muscle strength?
Greater strength with initial exertion and mild exercise (acetylcholine may build up and allow for improvement) but prolonged or marked exertion will result in worsening symptoms
What condition is a CT disease that is characterized by inflammation of skeletal muscle and skin?
Dermatomyositis
What lab findings do you expect in a patient with dermatomyositis?
Elevated CPK
Elevated ESR
Abnormal electromyography
Abnormal muscle biopsy
What are two classic microscopic findings of dermatomyositis?
Mixed B and T cell perivascular inflammatory infiltrate
Perifascicular muscle fiber atrophy
What is a characteristic rash seen in patients with dermatomyositis?
Periorbital heliotrope rash that is symmetric, purple-red, with macular eruption of the eyelids and the surrounding periorbital tissue.
Also the shawl sign.
What is Gottron’s sign and what condition is it associated with?
A purple-red papular rash over the dorsal aspect of the MCP and IP joints of the hand
It is also characteristic of dermatomyositis
What condition presents with symmetric proximal muscle weakness in the upper and lower extremities and neck flexors (ocular muscles are never involved)?
Polymyositis
What type of lymphocytes invade the muscle cells in polymyositis?
T8
What is the most obvious way to distinguish PM from DM?
PM has no skin problems
What are the microscopic findings with inclusion body myositis?
Focal areas of WBC and other inflammatory cells
Vacuoles in the muscle
Deposits of amyloid-related inclusions (beta amyloid, tau protein, and ubiquitin)
What lab value is elevated in inclusion body myositis?
CK
What benign tumor of striated muscle usually presents as a round mass in the region of the neck or head?
Rhabdomyoma
What is the most common soft tissue tumor in children?
Rhabdomyosarcoma
Rhabdomyosarcoma is a malignancy that arises from what lineage of cells?
Embryonic mesenchymal cells that possess the potential to develop into skeletal muscle
What is the third most common solid malignancy in the pediatric population?
Rhabdomyosarcoma
What are the histologic finds of a rhabdomyosarcoma?
Pleomorphic cells
Poorly differentiated
Interweaving bundles of spindle shaped cells with elongated hyperchromatic nuclei
Many mitoses
What muscles are most commonly affected by rhabdomyosarcoma?
The orbit of the eye or on the face, scalp, neck, and extremities
