Bones, Joints, & Soft Tissue Flashcards
The adult skeleton is constantly turning over, with 10% of the skeleton being replaced annually.
When is peak bone mass achieved?
Early adulthood, after cessation of skeletal growth
By the fourth decade of life, resorption occurs at a greater rate than formation, leading to decreased overall skeletal mass
______ is the receptor activator for NF-kB on osteoclast precursors that, when bound by its ligand, activates transcription factor NF-kB which is essential for the generation and survival of osteoclasts, leading to bone ______
RANK; breakdown
RANKL is expressed on ____ and ______ cells
Osteoblasts; marrow stromal cells
“Decoy” receptor made by osteoblasts that binds RANKL and prevents its interaction with RANK - thus resulting in continued bone formation
OPG (osteoprotegrin)
Role of WNT/beta-catenin in bone homeostasis
WNT proteins are produced by osteoprogenitor cells; they bind LRP5 and LRP6 receptors on osteoblasts, triggering activation of beta-catenin and production of OPG
_____ is produced by osteocytes and inhibits the WNT/beta catenin pathway
Sclerostin
Hormones involved in bone building vs. bone breakdown
Build: estrogen, testosterone, vit D
Breakdown: PTH, IL-1, glucocorticoids
________ receptor on osteoclast precursors stimulates tyrosine kinase cascade that is crucial for generation of osteoclasts
M-CSF
Defect in HOXD13 leading to clinical phenotype of short, broad terminal phalanges of first digits
Brachydactyly types D and E
Defect in RUNX2 leading to clinical phenotype of abnormal clavicles, wormian bones, and supernumerary teeth
Cleidocranial dysplasia
[AD inheritance; wormian bones are extra bones w/i cranial sutures]
Defect in FGFR3 leading to clinical phenotype of short stature with normal trunk length, rhizomelic shortening of limbs, frontal bossing, and midface deficiency
Achondroplasia
[most common skeletal dysplasia and a major cause of dwarfism; no change in longevity, intelligence, or reproductive status]
Defect in FGFR3 leading to clinical phenotype of severe limb shortening and bowing, frontal bossing, and depressed nasal bridge
Thanatophoric dysplasia
[die at birth or soon after]
COL2A1 defect affecting type 2 collagen leading to clinical phenotype of short trunk
Achondrogenesis type 2
Mutation in CLCN7 affecting carbonic anhydrase (CA2), leading to clinical phenotype of increased bone density, fragility, and renal tubular acidosis
Osteopetrosis with RTA
Most common inherited disorder of connective tissue, primarily affecting bone but also joints, eyes, ears, skin, and teeth (blue sclera, hearing loss, dental imperfections)
Osteogenesis imperfecta
Molecule affected in osteogenesis imperfecta
Alpha 1 and alpha 2 chains of type I collagen
Describe the specific collagen defect and inheritance pattern of osteogenesis imperfecta type 1
Decreased synthesis of pro-alpha1(1) chain
Abnormal pro-alpha1(1) or pro-alpha2(1) chains
[Collagen structure is normal, but present in smaller amounts]
Inheritance: Autosomal Dominant
Describe the major clinical features and prognosis associated with osteogenesis imperfecta type 1
Postnatal fractures Normal stature Skeletal fragility Dentinogenesis imperfecta Hearing impairment Joint laxity Blue sclerae
Prognosis: compatible with survival
Describe the specific collagen defect and inheritance pattern of osteogenesis imperfecta type 2
Abnormall short pro-alpha1(1) chain
Unstable triple helix
Abnormal or insufficient pro-alpha2(1)
Inheritance: mostly autosomal recessive
Describe the major clinical features and prognosis associated with osteogenesis imperfecta type 2
Death in utero or within days of birth
Skeletal deformity with excessive fragility and multiple fractures
Blue sclerae
Prognosis: perinatal lethal
T/F: with type 1 osteogenesis imperfecta, most fractures occur before puberty and decrease in frequency with age
True
Osteopetrosis is associated with a mutation in ______ which encodes proton pumps on the surface of osteoclasts.
This leads to a ______ _____ deficiency, which is required by osteoclasts and renal tubular cells
CLCN7
Carbonic anhydrase
Describe bone defects in osteopetrosis
Bones lack medullary cavity
Bulbous ends of long bones (erlenmyer flask shape)
Neural foramina are small and compress cranial nerves (leads to optic atrophy, deafness, facial paralysis, etc.)
Osteopetrosis may develop through autosomal recessive or autosomal dominant inheritance. Describe the autosomal recessive form
AR = Severe infantile type
More common in children of Mediterranean and Arab race
Results in cranial nerve deficits (optic atrophy, deafness, facial paralysis)
Postpartum mortality d/t fractures, anemia, and hydrocephaly
Osteopetrosis may develop through autosomal recessive or autosomal dominant inheritance. Describe the autosomal dominant form
AD = mild form, diagnosed in adolescence or adulthood
Characterized by repeated fractures, mild cranial nerve deficits, and anemia
Lysosomal storage diseases caused by deficiency in enzymes (usually acid hydrolases) that degrade dermatan sulfate, heparan sulfate, and keratan sulfate
Mucopolysaccharidoses
[leads to accumulation of mucopolysaccharides in chondrocytes and in extracellular space —> structural defects in articular cartilage —> short stature, chest wall abnormalities, and malformed bones]
Differentiate defining criteria for osteopenia vs. osteoporosis
Osteopenia = decreasd bone mass 1.0-2.5 SD below the mean
Osteoporosis = decreased bone mass at least 2.5 SD below the mean peak bone mass in young adults (aka osteopenia severe enough to increase risk of fracture)
Other than a bone mass at least 2.5 SD below the mean, what clinical event signifies progression of osteopenia to osteoporosis?
Atraumatic or vertebral compression fracture
2 most common forms of osteoporosis
Senile osteoporosis
Postmenopausal osteoporosis
Describe pathogenesis of senile osteoporosis, low turnover variant
Age-related changes include decreased proliferative and biosynthetic potential (aka an overall decreased capacity to make bone), AND a decreased cellular response to growth factors
How do changes in physical activity contribute to the pathogenesis of osteoporosis?
Mechanical forces stimulate normal bone remodeling. Load magnitude influences bone density — so resistance exercises are best for increasing bone density
Bone loss is seen with decreased physical activity including conditions of immobility, paralysis, astronauts in zero gravity, etc.
Genetic factors involved in the pathogenesis of osteoporosis
Few cases have a single gene defect in LRP5
Other genes that may be involved include RANKL, OPG, RANK, HLA focus, estrogen receptor gene, vit D receptor gene (involved in Wnt signaling)
What role does calcium nutritional state play in the pathogenesis of osteoporosis?
Adolescent girls have insufficient calcium intake during period of rapid growth, thus restricting their peak bone mass until ultimately achieved (especially if dieting or have an eating disorder)
[note: calcium deficiency, increased PTH, and decreased vit D may also contribute]
Hormonal influences play a big role in pathogenesis of postmenopausal osteoporosis — leading to ACCELERATED bone loss. 10 years after menopause, there are yearly reductions of up to 2% cortical and 9% cancellous bone. 30-40 years after menopause 35% cortical and 50% of cancellous bone are lost.
Describe the major hormone involved and how it affects pathogenesis in the high turnover variant of this condition
Estrogen deficiency —> increased resorption and formation. In the high turnover variant — Formation < resorption
Decreased estrogen increases secretion of inflammatory cytokines by blood monocytes and bone marrow cells, which stimulate osteoclast recruitment and increased RANKL, decreased OPG, leading to decreased osteoclast proliferation and prevention of osteoclast apoptosis
Inflammatory cytokines implicated in postmenopausal osteoporosis
IL-1
IL-6
TNF-alpha
Effect of standard breast cancer treatments such as adjuvant chemo or hormonal therapy on risk of osteoporosis
Increased bone loss, leading to increased risk of osteoporosis
Osteoporosis is morphologically normal bone, just decreased in quantity. Postmenopausal osteoporosis is associated with increased osteoclast activity, especially in bones with increased surface area such as cancellous bones of the vertebral bodies. The result is perforation, thinning, and loss of interconnections within ______, leading to microfractures and vertebral collapse
Trabeculae
In ______ osteoporosis, the morphology consists of cortical thinning by subperiosteal and endosteal resorption, leading to widening of Haversian system (may mimic cancellous bone)
Senile
Genetic, nutritional, and environmental risk factors for osteoporosis
Genetic: caucasian, light colored hair and eyes
Nutrition: low calcium intake, high phosphorus intake
Environmental: smoking
How is osteoporosis typically diagnosed?
Bone mineral density test (DEXA-scan) — early signs may not even show up on Xray (need >30% bone loss to detect on plain film)
Blood tests may be done to determine secondary causes of osteoporosis, such as renal or hepatic failure, hyperthyroidism, etc
Clinical course of osteoporosis includes vertebral fractures, loss of height due to increased lumbar lordosis and kyphoscoliosis, and potential fracture complications such as PE and PNA.
How is osteoporosis treated?
Bisphosphonates — decrease osteoclast activity and induce osteoclast apoptosis
[other options include hormone therapy, anti-RANKL agents, etc]
Acquired disorder presenting in late adulthood - resulting in increased BUT disordered and structurally abnormal bone mass; the axial skeleton and femur are involved in up to 80% of cases; avg age at dx is 70
Paget disease (aka osteitis deformans)
The pathogenesis of Paget disease is considered both genetic and environmental. Describe genetic basis for this condition
40-50% familial
5-10% sporadic mutations in SQSTM1 gene —> increased activity of NF-kB —> increased osteoclast activity
Describe hallmark morphology of Paget disease
Mosaic pattern of lamellar bone, seen in sclerotic phase
Jigsaw-like appearance with prominent cement lines = haphazardly oriented units of lamellar bone
3 phases of paget bone changes/morphology
- Initial lytic phase — large osteoclasts with 100 nuclei (normal is 10-12 nuclei)
- Mixed phase — clasts persist, but lots of blasts also; primarily osteoblastic at end of this stage
- Final phase — burned-out quiescent osteosclerotic stage characterized by coarsely thickened trabeculae and cortices that are soft and porous, lacking structural stability; fractures easily
Clinical features of paget disease
Weight bearing leads to bowing of femurs and tibia, distorting the femoral head and leading to secondary osteoarthritis
Chalk-stick type fractures of long bones of legs
Compression fractures of spine produce spinal cord injury and kyphosis
Hypervascularity of paget bone warms the overlying skin. Increased blood flow acts as arteriovenous shunt leading to high-output heart failure
In paget disease, there is usually ________ serum alk phosphatase, ______ calcium, and _____ phosphorus
Increased; normal; normal
Rickets and osteomalacia are both manifestations of _____ deficiency or its abnormal metabolism, leading to impairment of mineralization and resultant accumulation of unmineralized matrix
Vit D
What is the difference between rickets and osteomalacia?
Rickets = children; interferes with deposition of bone in growth plate
Osteomalacia = adults; bone formed during remodeling is undermineralized, predisposing to fractures
Frontal bossing Squared off head Rachitic rosary of ribs Pigeon chest Lumbar lordosis Bowed legs
Rickets
PTH leads to ______ of osteoclasts
Activation
[thus hyperparathyroidism leads to significant skeletal changes related to unabated osteoclast activity]
Untreated primary hyperparathyroidism leads to what 3 primary skeletal abnormalities?
Osteoporosis
Brown tumors
Osteitis fibrosa cystica (von recklinghausen disease of bone)
Where is osteoporosis most severe with hyperparathyroidism?
Phalanges, vertebrae, and proximal femur
[this is because increased osteoclast activity is most prominent in cortical bone (subperiosteal and endosteal surfaces), medullary bone not spared]
_____ _____ = osteoclasts tunnel into and dissect centrally along length of trabeculae creating appearance of railroad tracks
Dissecting osteitis
What are “brown tumors” (associated with hyperparathyroidism)
Bone loss predisposes to microfracture that elicits influx of macrophages and ingrowth of reparative fibrous tissue creating a mass of reactive tissue
[tumors are brown d/t vascular, hemorrhage, and hemosiderin deposition; can undergo cystic degeneration]
Skeletal changes that occur in chronic renal disease, including those associated with dialysis, including osteopenia/osteoporosis, osteomalacia, secondary hyperparathyroidism, and growth retardation
Renal osteodystrophy
Histologic bone changes associated with renal osteodystrophy
High-turnover osteodystrophy — increased bone resorption and bone formation; resorption > formation
Low-turnover or aplastic disease — adynamic bone (little osteoclastic and blastic activity); less commonly osteomalacia
Mixed: areas of high turnover and low turnover
3 mechanisms by which renal disease causes skeletal abnormalities
- Tubular dysfunction — RTA low pH dissolves hydroxyapatite —> demineralization
- Generalized renal failure —> decreased phosphate excretion and thus chronic hyperphosphatemia, hypocalcemia, and secondary hyperparathyroidism
- Decreased production of secreted factors (vit D3)
In what pt population is renal osteodystrophy most serious?
Kids — because their bones are still growing so deformities are more significant
Fracture in which overlying skin is intact
Simple fracture
Fracture in which bone communicates with skin surface
Compound fracture
Fracture in which bone is fragmented
Comminuted
Fracture in which ends of bone at the fracture site are not aligned
Displaced fracture
Slowly developing fracture that follows a period of increased physical activity in which bone is subjected to repetitive loads
Stress fracture
Fracture extending only partially through bone, common in infants when bones are soft
Greenstick fracture
Fracture involving bone weakened by an underlying disease process, such as a tumor
Pathologic fracture
Healing of fracture begins immediately, as rupture of blood vessels results in a ______ which fills the fracture gap and surrounds the area of bone injury.
Clotted blood forms fibrin mesh, sealing the site and creating framework for influx of inflammatory cells and fibroblasts. Degranulated platelets and migrating inflammatory cells release ____, _____, and ____ which activate osteoprogenitor in the periosteum, medullary cavity, and surrounding soft tissues, and stimulate osteoclastic and osteoblastic activity
Hematoma
PDGF; TGF-B; FGF
In terms of fracture healing, by the end of the first week there is a soft tissue _____ or ______ which will be fusiform and predominantly uncalcified
Callus; procallus
[overall stages are 1. Hematoma formation, 2. Callus formation, 3. Callus ossification, 4. Bone remodeling]
Infarction of the bone and marrow caused by vascular insufficiency through mechanical injury to blood vessels, thromboembolism, external pressure on vessels, or venous occlusion
Osteonecrosis (avascular necrosis)
2 most common causes of osteonecrosis
Fractures
Corticosteroid tx
What type of infarct associated with osteonecrosis causes pain initially associated only with activity, later becoming constant, and often collapse potentially leading to severe secondary osteoarthritis?
Subchondral infarcts
_____ infarcts associated with osteonecrosis are usually small and clinically silent, except they occur with Gaucher disease, dysbarism (“bends”), and ___________
Medullary; sickle cell anemia
Regardless of etiology, medullary infarcts are geographic and involve trabecular bone and marrow. Why isn’t the cortex affected in these cases?
Because of the collateral flow to the cortex
Describe “dead bone” associated with osteonecrosis morphology
Empty lacunae surrounded by necrotic adipocytes that frequently rupture, releasing fatty acids that bind calcium forming insoluble calcium soaps; osteoclasts resorb necrotic trabeculae
Trabeculae that remain act as scaffolding for deposition of new bone = “creeping substitution”
________ = inflammation of bone and marrow, virtually always following infection and may be a complication of systemic infection, but frequently a primary solitary focus of disease; can be due to viruses, parasites, fungi, and bacteria, but mostly caused by _______ and ______
Osteomyelitis; pyogenic bacteria; mycobacteria
What causes 80-90% of culture positive osteomyelitis?
Staphylococcus aureus
E.coli, pseudomonas, and klebsiella more commonly cause osteomyelitis in pts with UTIs or IV drug users. H.influenzae and group B strep are also frequent pathogens associated.
Sickle cell patients are at increased risk for osteomyelitis due to _________.
Patients with a MAC complement deficiency are at increased risk of osteomyelitis due to __________
Salmonella
Neisseria
In acute osteomyelitis, bacteria proliferate and neutrophils are present. There is often necrosis of bone cells and marrow within 48 hours. In kids, the periosteum is loosely attached, and sizable ______ _____ may form and dissect for long distances along bone surface.
Subperiosteal abscesses
A ________ is dead bone following subperiosteal abscess due to osteomyelitis. Rupture of the periosteum in these cases may lead to soft tissue abscess which can channel to becoming a draining _____
Sequestrum; sinus
Clinical course of acute osteomyelitis in infants
Epiphyseal infection spread through articular surface or along capsular and tendoligamentous insertions into joints —> septic or suppurative arthritis
Can destroy articular cartilage leading to permanent disability
Chronic osteomyelitis is characterized by release of cytokines by chronic inflammatory cells that stimulate osteoclastic resorption, ingrowth of fibrous tissue, and deposition of reactive bone at the periphery.
During the chronic phase of osteomyelitis, an _________ is newly deposited bone that forms a shell of living tissue around the segment of devitalized bone
Involucrum
During the chronic phase of osteomyelitis, a ____ ____ may form which is a small interosseous abscess frequently involving the cortex and is walled off by reactive bone
Brodie abscess
The chronic phase of osteomyelitis may be characterized by sclerosing osteomyelitis of Garre — what is that???
Osteomyelitis of the jaw, associated with extensive new bone formation that obscures much of the underlying osseous structure
________ osteomyelitis is usually blood-borne, originating from a focus of active visceral disease during initial stages of primary infection. Bone infection may persist for years before detected, and is histologically characterized by caseous necrosis and granulomas
Mycobacterial osteomyelitis
Mycobacterial osteomyelitis of the spine in which infection breaks through intervertebral discs to infect multiple vertebrae and soft tissues, leading to permanent compression fractures —> scoliosis or kyphosis and associated neurologic deficits
Tuberculous spondylitis (Pott disease)
Bone abnormalities associated with congenital syphilis
Saber shin — massive reactive periosteal bone deposition on medial and anterior surfaces of the tibia
[Bone lesions appear about 5th month gestation and are fully developed at birth]
Bone lesions associated with acquired syphilis
Saddle nose, palate, skull, and extremities (especially long tubular bones like the tibia)
[bone disease may begin early in tertiary stage, 2-5 years after initial infection]
Benign cartilage-forming tumor affecting metaphysis of long bones in ages 10-30, characterized by bony excrescence with cartilage cap
Osteochondroma
Benign cartilage-forming tumor affecting small bones of hands and feet in ages 30-50 characterized by circumscribed hyaline cartilage nodule in medulla
Chondroma
Malignant cartilage-forming tumor, often affecting pelvis or shoulder, in ages 40-60 characterized by extension from medulla through cortex into soft tissue, chondrocytes with increased cellularity, and atypia
Chondrosarcoma
Benign bone-forming tumor affecting metaphysis of long bones in ages 10-20 characterized by cortical, interlacing microtrabeculae of woven bone
Osteoid osteoma
Malignant bone-forming tumor affecting metaphysis of distal femur and/or proximal tibia in ages 10-20 characterized by extension from medulla to lift periosteum, malignant cells producing woven bone
Osteosarcoma
Malignant tumor of unknown origin affecting diaphysis of longbones in ages 10-20 characterized by sheets of primitive small round cells
Ewing sarcoma
Most common benign bone tumor, 85% of which are solitary and affecting men 3x more commonly than women
Osteochondroma (aka exostosis)
Osteochondromas typically present in early adulthood, but may present younger in autosomal dominant _____ _____ _____, which progresses to _______ in 5-20%
Multiple hereditary exostosis; chondrosarcoma
Benign hyaline cartilage, solitary metaphyseal lesions of hands and feet, may be within medullary cavity or on surface
Chondroma (enchondroma when in medullary cavity)
Multiple enchondromas = _______ syndrome
Ollier
________ _______ = Multiple enchondromas + angiomas —> increased risk of chondrosarcoma and other malignancies
Mafucci syndrome
Second most common malignant matrix producing tumor of bone, 2:1 male predominance, usually 40s or older, affecting axial skeleton
Chondrosarcoma
Chondrosarcomas tend to invade locally as a painful enlarging mass and may metastasize. 70% of grade 3 spread hematogenously, especially to the ____
Lungs
GI polyposis syndrome occurring at mean ages 10-15 due to mutation in APC resulting in multiple GI adenomas as well as osteomas, thyroid and desmoid tumors, and skin cysts
Gardner syndrome
Demographics and clinical features of osteoid osteoma
Young men, teens and 20s
Clinically: Painful, usually worse at night, classically responds to aspirin and NSAIDs
[usually affects appendicular skeleton — 50% of the time femur or tibia]
By definition, osteoid osteomas are <2 cm in greatest dimension. Anything greater than 2 cm would be classifed as an _______
Osteoblastoma
Morphologically, osteoid osteomas are characterized by a central nidus of translucent woven bone surrounded by a rim of osteoblasts. What is the primary radiographic clue that it is an osteoid osteoma?
Thick rind of reactive cortical bone
Osteoblastomas are bigger than osteoid osteomas (>2 cm) and typically involve the _____ ______. They do not show a bony reaction, and are characterized by an achy pain that does NOT respond to aspirin
Posterior spine
Most common primary malignant tumor of bone, presenting as a painful enlarging mass
Osteosarcoma
Age distribution of osteosarcoma
Bimodal age distribution — 75% occur in males <20 y/o
2nd peak in older males with Pagets, prior radiation (secondary osteosarcoma)
Most commonly affected area in osteosarcoma
Around the knee (60-75%)
Genes associated with development of osteosarcoma
Increased risk if Rb gene mutation (70% of sporadic osteosarcoma)
Other genes involved include TP53 (Li-Fraumani syndrome), INK4a, MDM2, and CDK4
Characteristic x-ray finding associated with osteosarcoma
Mixed lytic and blastic mass + CODMAN triangle (elevation of periosteum)
Prognosis of osteosarcoma
Spreads early to lungs (10-20% at dx)
Surgery and chemo result in 60-70% survival at 5 years
Spreads hematogenously to lungs, bones, and/or brain
Demographics of ewing sarcoma family tumors (ESFT)
80% occur in ages <20
Striking predilection for caucasians
2nd most common bone sarcoma in children
Ewing sarcoma family tumors are small blue round cell tumors that are undifferentiated. With neural differentiation, they are associated with _____
PNET (primitive neuroectodermal tumor)
Clinical presentation of ewing sarcoma family tumors
Painful enlarging mass; frequently tender, warm, and swollen (fever, increased ESR) — mimics infection!
Locations affected by ewing sarcoma family tumors, and their characteristic finding on x-ray
Diaphysis of long bones, esp femur and flat bones (arises in medullary cavity and invades cortex)
On x-ray: periosteal reaction shows up as reactive bone in “onion skin” fashion
t(11;22)(q24:q12) resulting in fusion gene ________ is found in 85% of ________
EWS-FL11; Ewing Sarcoma Family Tumors (ESFT)
ESFT are aggressive malignancies treated with neoadjuvant chemo followed by surgical excision with or without irradiation. The advent of effective chemo has achieved 5 year survival of 75% and long-term cure in 50%. What is an important prognostic finding in this condition?
The amount of chemotherapy-induced necrosis
Fibrous dysplasia is a benign proliferation of fibrous tissue and bone that does not mature and may be a developmental anomaly. What are the clinical features associated with fibrous dysplasia?
Mostly early adolescence (stops enlarging at growth plate closure); M=F
1/3 craniofacial bones, 1/3 femur or tibia, and 1/3 ribs
Usually incidental finding, but can cause pain, fracture, or discrepencies in limb length
Radiographic appearance of fibrous dysplasia
Ground glass with well-defined margins
Disease characterized by GNAS mutation leading to unilateral bone lesions, pigmented skin lesions (cafe au lait), and precocious puberty in females (+other endocrinopathies)
McCune-Albright disease
Syndrome characterized by fibrous dysplasia (usually polyostotic), multiple skeletal deformities in childhood; may also show soft tissue myxomas (IM)
Mazabraud syndrome
Multinucleated osteoclast-type giant cell tumor that is benign but locally aggressive, arising in epiphysis but may extend into metaphysis causing arthritis like symptoms, and tends to recur after curettage
Osteoclastoma
The most common form of skeletal malignancy is metastasis. Spread may occur via direct extension, lymph/hematogous, or intraspinal seeding. What primary tumor sites most commonly spread to bone in adults vs. kids?
Adults — 75% from prostate, breast, kidney, lung
Kids — neuroblastoma, wilms, osteosarcoma, ewing, rhabdomyosarcoma
Radiography of metastasis to bone may show lytic lesions which are characteristic of primary tumors of renal, lung, GI, or melanoma origin. Alternatively, radiography may show blastic (bone forming) lesions which is characteristic of ______ ______
Prostatic adenocarcinoma
Primary or idiopathic Osteoarthritis/DJD is typically due to _______ and is considered oligoarticular (affects few joints). It tends to affect ____ and _____ in women, and ____ in men
Aging; hands; knees; hips
Secondary osteoarthritis may occur in what conditions?
DM, hemochromatosis, thyroid, acromegaly, charcot
[predisposing conditions include joint deformity, trauma, marked obesity]
Osteoarthritis/DJD is a disease of CARTILAGE wear and tear. What are clinical features of DJD?
Evening stiffness, crepitus, limited ROM, gets worse with use
Bouchard’s nodes vs. heberden nodes
Bouchard’s nodes = DJD in PIPs
Heberden nodes = DJD in DIPs
Pathogenesis of osteoarthritis/DJD begins when water content of matrix increases and concentration of proteoglycans decreases, leading to cracks in matrix, eventually leading to “joint mice” which are hunks of sloughed off ________.
Subchondral bone is then exposed and rubbed smooth in a process called _______ (causes bone-on-bone pain)
The bone then tries to buttress the stress, and microfractures and cysts develop. The formation of ______ may lead to nerve root compression and radicular pain
Cartilage
Eburnation
Osteophytes
_________ = inflammation, pannus, eroding cartilage, fibrous ankylosis, bony ankylosis
________ = bony spurs, no ankylosis, subchondral cyst, subchondral sclerosis, osteophyte, thinned and fibrillated cartilage
[2 types of arthritis]
Rheumatoid arthritis
Osteoarthritis
Demographics of RA
Peaks 2nd-4th decades
3:1 female predominance
RA is associated with destruction of articular cartilage and _____, which is joint stiffness due to abnormal adhesion and rigidity (may be result of injury or disease)
Ankylosis
Joint distribution and clinical features of RA
Symmetrical distribution, small joints
Joints are swollen, warm, and painful
Characterized by morning stiffness or “gelling” after rest — may last longer than 1 hr in active disease
Boutonniere vs. swan-neck deformities
Boutonniere = hyperextension of DIP, flexion of PIP
Swan-neck = hyperextension of PIP, flexion of DIP
[both are seen in RA]
2 other hand deformities seen in RA other than boutonniere and swan-neck
Ulnar deviation of fingers
Radial deviation of wrist
RA joint pathology is characterized by _______ which is edematous, thickened, hyperplastic synovium; synovial hypertorphy with villi; and dense_____ aggregates
Pannus; lymphoid
What are rheumatoid nodules?
Deformities on extensor surfaces at pressure points
Morphologically characterized by central necrosis and palisading histiocytes
Autoimmune, T-cell response initiated by environmental factors in predisposed without specific antibodies present, leading to pathologic changes in ligamentous attachments rather than synovium
Seronegative spondyloarthropathies
Seronegative spondyloarthropathies are negative for rheumatoid factor (RF), but are commonly associated with ______
HLA-B27
HLA-B27 -related seronegative spondyloarthropathy affecting vertebrae and SI joints in ages 20-30s with complications including uveitis, aortitis, and amyloidosis, as well as possibility of peripheral joint involvement
Ankylosing spondylitis
Triad of reactive arthritis
- Arthritis
- Urethritis or cervicitis
- Conjunctivitis
80% of reactive arthritis is associated with molecular marker _______, occurs in ____ in their 20s and 30s, as well as individuals with HIV; often with hx of prior GI or GU infections
HLA-B27; Men
Organisms implicated in enteritis-associated arthritis
Yersinia
Salmonella
Shigella
Campylobacter
[LPS stimulates immune response —> knees and ankles usually]
HLA-B27-related seronegative spondyloarthropathy affecting peripheral and axial joints, ligaments, and tendons; characterized by “pencil in cup” deformity of DIPs, frequent remissions, nail thickening and pitting and/or onycholysis
Psoriatic arthritis
Organisms that cause suppurative arthritis in <2 y/o vs. older kids and adults
<2 y/o: H.influenzae
Older kids and adults: staph aureus, gonococcus late adolescent, early adult
[gonococcal arthritis is more prevalent in sexually active women, increased risk in MAC def]
Clinical features of suppurative arthritis
Acutely painful, swollen joint with restricted range of motion [mycobacterial has more insidious onset]
Fever, leukocytosis, elevated ESR
Joint aspiration is diagnostic — purulent fluid
90% non-gonococcal cases of suppurative arthritis involve single joint — most commonly the ____
Knee
[followed by hip, shoulder, elbow, wrist, SC joint]
note: knee is also most common affected in mycobacterial and lyme disease supp arthritis
Tick-borne suppurative arthritis
Lyme disease (borrelia burgdorferi) — 60-80% develop days or weeks after skin lesion
Viral causes of suppurative arthritis
HIV, HBV, HCV, EBV, parvo B19, rubella
Gout is characterized by transient attacks of acute arthritis initiated by crystallization of ____________ within and around joints
Monosodium urate (MSU)
[precipitation MSU into joint —> cytokines that recruit leukocytes]
Precipitation of MSU in gout requires overproduction or reduced excretion — thus plasma levels are ______
> 6.8 mg/dL
Risk factors for gout
Age (gout appears w/ 20-30 years of hyperuricemia)
Genetic predisposition
Heavy alcohol consumption
Obesity
Drugs (thiazides)
Lead toxicity (saturnine gout)
Gout may be classified as primary (90%) or secondary (10%). What are the major causes of primary gout?
Unknown enzyme defects (85-90% of cases)
Known enzyme defects (e.g., partial HGPRT def)
3 major causes of secondary gout
Increased nucleic acid turnover (e.g., leukemia) —> increased uric acid production
Chronic renal dz —> decreased uric acid excretion
Congenital (e.g., Lesch-Nyhan syndrome, HGPRT deficiency) —> increased uric acid production
Why does gout tend to affect peripheral joints?
Lower temp of peripheral joints favors crystallization
Morphologic finding that is pathognomonic for gout
Gouty tophus and polarized urate crystals
Condition characterized by crystallization of calcium pyrophosphate that forms chalky, white, friable deposits that morphologically show oval blue-purple aggregates
Calcium pyrophosphate crystal deposition (CPPD) aka Pseudo-gout aka Chondrocalcinosis
Cyst that forms in joint capsule or tendon sheath, typically on the wrist with firm fluctuant pea-sized translucent nodule as the result of cystic or myxoid degeneration (cyst wall lacks cell lining)
Ganglion cyst
A synovial cyst is a herniation of synovium through joint capsule. One type of this is ________ which occurs in the popliteal space and is associated with RA
Baker cyst
Tumor associated with t(12;16)(q13;p11) FUS-DDIT3 gene fusion leading to arrests in adipocytic differentiation
Liposarcoma — myxoid and round-cell type
Tumor associated with t(x;18)(p11;q11) w/chimeric transcription factors, interrupts cell cycle control
Synovial sarcoma
Tumor associated with t(2;13)(q35;q14) and/or t(1;13)(p36;q14) affecting PAX genes —> disruption of skeletal muscle differentiation
Rhabdomyosarcoma-alveolar type
Most common soft tissue tumor of adults, characterized by encapsulated mass of normal appearing adipose tissue
Lipoma
Most common histologic variant of liposarcoma
Myxoid (intermediate)
Self-limited fibroblastic and myofibroblastic proliferation; young adults upper extremity; spontaneously regresses
Nodular fasciitis
Fibromatoses are nfiltrative local deformities; M>F; may affect palms as ____________, plantar in young pts without contracture, or penile as ________ disease
Dupuytren contracture; peyronie disease
3 subtypes of rhabdomyosarcoma
Alveolar (kids) — FOXO1 fusion to PAX3 (2;13) or PAX7 (1;13)
Embryonal (kids) — rhabdomoblasts with cross striations, sarcoma botryoides
Pleomorphic (adults)
Benign smooth muscle tumor often occurring in the uterus (fibroid); associated with hereditary leiomyomatosis and renal cell cancer syndrome
Leiomyoma
Smooth muscle tumor of adults (makes up 10-20% of ST sarcomas), W>M, affecting extremities and retroperitoneum
Leiomyosarcoma
Tumor of uncertain origin, may be found adjacent to a joint but also found in chest wall, head and neck. 4th most common sarcoma. + for keratins, epith markers, poor prognosis with mets to lung common
Synovial sarcoma
[misnomer — does not come from synovium, thats just where tumor was first found]
