Flashcards in Connective Tissue Deck (115):
What are two types / patterns of bone and what forces do they resist?
Cortical / compact: outer shell of bone. Resists bending
Cancellous / spongy bone: inner trabecular bone. Resists compression. more metabolically active.
What is produced by osteoblasts that inhibits RANK / RANKL interaction?
2 types of bone formation
Intramembranous: flat bones: mesenchyme -> osteoprogenitor -> osteoblast
Endochondrial: long bones: cartilage model -> perichondrium -> bone collar -> primary ossification center
3 joint types
Amphiarthrodial (cartilaginous): intervertebral disc
Synarthroses (fibrous): skull sutures
How do red and yellow bone marrow appear on MRI?
On T1 weighted image:
Red marrow is gray
Yellow marrow is white
Is osteoporosis an issue of quality or quantity of bone?
Existing bone is qualitatively normal
5 disease states that can -> osteoporosis
In osteopenia, what is the relationship of cortical bone to total bone diameter?
Normally cortical bone constitutes 50% or more of the total bone diameter
In osteopenia, cortices thin, so ratio of cortical / medullary bone decreases.
What are radiologic features of degenerative joint disease (osteoarthritis)?
Loss of joint space (cartilaginous fibrillation and erosion)
Bony eburnation (increased cellularity and vascularization of subchondral bone)
Subchondral cysts (synovial fluid intrusion or bone contusion)
Osteophytes (revascularization of remaining cartilage and capsular traction -> bone spurs)
What is a vacuum disc?
collection of gas within intervertebral disc space due to degeneration of disc material.
What is spondylolisthesis?
Subluxation forward displacement of a vertebra (usually 5th lumbar)
complication of DJD of the spine
What is Schmorl's Node?
Vertical displacement of intervertebral disc material into adjacent vertebral body.
Usually benign, but may contribute to pain
What are enthesophytes?
Calcification of ligamantal attachment to bone
What are the stages of fracture repair?
1. Procallus: inflammatory stage, lasts several days following fx. hemorrhage + necrosis -> inflammation + edema -> granulation + osteoprogenitor cells -> organizing hematoma
2. Bony callus
What are pathological features of osteomyelitis?
1. Sequestrum: dead, necrotic bone - ID by empty lacunae
2. Involucrum: formation of sheath of new bone around dead bone by osteoblasts in periosteum (seen w/ chronic osteomyelitis
What are some genetic factors in systmic sclerosis?
Anti-centromere Ab: CREST
Anti-topoisomerase I (scl-70): severe disease in blacks
TGF-B1 polymorphisms: pulmonary fibrosis
Fibrillin-1 polymorphisms: Chocktaw Native Americans
What is microchimerism?
Concept in pathogenesis of scleroderma
Mother and fetal cells pass bidirectionally through placenta and persist.
Later cells become activated -> GVHD type reaction -> systemic sclerosis
What are functions of the sacral nerves?
S1: ankle eversion
S2-4: bowel and bladder control
What are components of the intervertebral discs?
Annulus fibrosis: T1 collagen
Nucleus pulposis: GAGs and low T2 collagen, >85% water
What conditions predispose to alanto-axial instability?
What is Klippel-Feil syndrome?
Multiple fused cervical vertebrae due to failed segmentation of cervical somites.
Assoc. w/ other abnormalities: cardiac, renal, brain stem
What direction does the curve most often deviate in infantile idiopathic scoliosis?
To the left in pts. birth - 3yrs.
Associated with other defects (usually very sick patients): heart, renal, etc.
In older patients, left curving scoliosis requires MRI to seek other major congenital defects.
In idiopathic adolescent scoliosis, what degree requires treatment?
30: bracing, surgery depending on case
90 deg: heart and lung impairment
With what conditions are neuromuscular scoliosis associated?
Neuromuscular: Cerebral Palsy, Muscular Dystrophy
What is the most common cause of congenital scoliosis?
Unilateral unsegmented bar deformity: Unilateral failure of vertebral segmentation
What is Scheurmann's disease?
Thoracic hyperkyphosis: >5deg wedging at 3 consecutive vertebrae
Idiopathic. Treated with bracing and/or surgery
What is the most common cause of back pain in children?
Spondylolysis: fatigue fracture of pars interarticularis
Seen in FB players, gymnasts
Usually at L5 - S1
What are the most common organisms in osteomyelitis in the following age groups:
Newborn, non-newborn - 4 yrs, >4 yrs
Newborn: GBS, Neisseria
non-newborn - 4 yrs: S. aureus, H. influenzae
>4 yrs: S. aureus, Pseudomonas if foot infection
What is the most frequent organism involved in osteomyelitis in children w/ sickle cell?
S. aureus most common
Salmonella is frequently associated
What is the most common joint affected in pediatric septic joint?
What is Legg-Calve-Perthe's Disease?
Pediatric avascular necrosis of the hip
Due to early stenosis of ligamentum teres (umbilical vein), femoral circumflex aa. not ready to take over
Bilateral in 10-15%
Crescent sign on xray
What is slipped capital femoral epiphysis?
Occurs during growth spurt
Separation of epiphysis from metaphysis along growth plate
No gender correlation
Height, weight, race (black)
What is Pott Disease?
Tuberculous Osteomyelitis affecting vertebral bodies
Back pain, fever, night sweats, weight loss
2 complications that can arise out of chronic tuberculous osteomyelitis
1. Secondary (AA) Amyloidosis
2. Squamous cell carcinoma of a draining sinus tract
What is the genetic cause of achondroplasia?
FGF-3 receptor mutation -> arrested growth plate development
Usually sporadic, assoc. with advanced paternal age
Also AD inheritance
2 main genetic variants of osteopetrosis
AR: severe firn
AD: less severe, but more common
Cause of osteopetrosis
Defective osteoclasts - Carbonic anhydrase II mutation -> inability to acidify pits -> lack of resorption -> brittle, dense bone
What exam / lab findings are common in multiple myeloma?
blood smear: rouleaux formation
urine: bence jones proteinuria, nephrotic casts
Osteoma: benign or malignant? location? age?
Benign bone growth. usually noticed in children. flat bones, esp. skull. asymptomatic.
Symptoms of osteoid osteoma? who affected? benign / malig?
Presents in adolescents, m>f, with focal pain in a long bone that is worse at night and relieved with NSAIDs.
benign. radiolucent core of vascular immature woven bone w/ thickened reactive bone surrounding.
Excision is curative
What is osteochondroma?
May be sporadic or hereditary (AD and multiple)
Growth derived from growth plate w/ hyaline cartilage cap, usually grows from metaphysis of femur near knee.
Stops growing w/ growth plate fusion around puberty.
What is enchondroma?
Usually seen in small tubular bone of hand or foot
Intramedullary growth of benign hyaline cartilage
What is a fibrous cortical defect?
Benign growth of benign fibroblasts and macrophagesw/in metaphysis of long bone
Fibrous defect: small, regresses ; Non-ossifying fibroma: large, persists.
Thin cortex -> risk of fracture
What is fibrous dysplasia?
3 variants: monostotic, polyostotic w/o endocrine dysfunction, polyostotic w/ endocrine dysfunction
GNAS gene gof mutation
ground glass appearance. fibroblasts mixed w/ immmature bone
What is the most common non-hematopoietic bone malignancy?
Common radiographic feature of osteosarcoma
What is seen clinically w/ osteosarcoma?
History of paget's, bone infarct, radiation, familial retinoblastoma
high alkaline phosphatase, Codman's triangle on radiogram
What bones are most often affected in chondrosarcoma? what age group?
proximal skeleton: pelvis, shoulder, spine
Usually middle-aged to older adults, m>f
What is the genetic association for Ewing Sarcoma?
t(11;22) -> fusion of EWS gene with a transcription factor -> oncoprotein that stimulates cell proliferation
What population is usually affected by Ewing sarcoma?
Children, W>B, M>F
When are giant cell tumors usually diagnosed?
Young adults after closure of growth plate
What malignancies commonly metastasize to bone?
Lung, breast, prostate, kidney, thyroid
What is a fragility fracture?
Fall from equal to or less than standing height -> fracture. Normal bone density this is not a concern, but occurs in osteoperosis
What are the most common osteoporotic fractures?
2. Colles: distal radius
3. Hip / proximal femur
2 types of osteoporosis
Type I: post menopausal - mostly trabecular bone - rapid loss in 1st five yrs. of menopause
Type II: aging related - trabecular and cortical bone, gradual decline in density
In terms of race and gender, who is most at risk for osteoporotic fracture (lowest bone density)?
White women (lowest density, highest risk)
Black men (highest density)
Serum markers of bone formation
2. Bone specific Alkaline Phosphatase
Serum markers of bone resorption
1. free deoxypyridinoline
2. urinary collagen type I cross-linked N-telopeptide (Urine NTX)
40 high (used clinically)
3. urinary collagen type I cross-linked C-telopeptide
How is the growth plate affected in rickets?
-columnar arrangement of chondrocytes elongated and distorted
-lack of calcification of zone of maturation
2 types of synoviocytes
Type A: from macrophages - "cleaners"
Type B: from fibroblasts - "secretors"
In testing synovial fluid, what 3 tubes should be drawn and for what purposes?
Purple: Cell count
Red: Gram and culture / sensitivity
In a cell count of synovial fluid what cells are normally seen and what numbers are seen w/ what conditions?
RBC: 0 is normal, if present: hemarthrosis
WBC: 50,000: infectious inflammation
Acute: PMN >75%
Subacute: PMN <25%
what is meant by positive and negative birefrengence?
Crystal being examined is aligned w/ slow ray of red plate compensator.
Positive: Slow ray of crystal aligns w/ slow ray of plate (slow+slow) -> blue is seen
Negative: Fast ray of crystal aligns w/ slow ray of plate (fast - slow) -> yellow is seen
Characteristics of Monosodium Urate vs. Calcium Pyrophosphate Dihydrate crystals when viewed under polarized microscopy
MSU: needle shaped crystals - strongly negative birefringence
CPPD: rhomboid shaped crystals - weakly positive birefringence
In cases of septic arthritis, infections of what joints constitute surgical emergencies?
Hip and Shoulder
What are symptoms of septic arthritis caused by N. gonorrhea?
Young, sexually active patient
Hot, swollen joint
Pustular lesions on palms and soles
In a case of suspected Gonococcal septic arthritis, what is included in a proper workup?
Culture of cervix / urethra, rectum and throat
Gram stain, culture and susceptibility of synovial fluid (usually neg.)
Joint tap: WBC 50,000 - 100,000
What should be included in a workup for suspected TB septic arthritis?
2 drugs known to contribute to gout
Low dose aspirin: inhibits UA excretion
What constitutes hyperuricemia?
Males >7 mg/dL
What is the pathophysiology of gout?
Uric acid crystals shed into joint
Coated w/ IgG or ApoE
If coated w/ IgG, react w/ Fc receptors on PMN / Mac -> engulfment
Phagolysosome formation around crystal
Hydrogen bond in crystal matrix interact w/ membrane -> lysis and inflammation
What are the 3 stages of gout?
1. asymptomatic hyperuricemia
2. acute gouty arthritis
3. chronic tophaceous gout
What are 4 types of kidney disease associated with gout?
1. urate nephropathy
2. uric acid nephropathy
3. kidney stones
4. lead nephropathy (saturnine gout)
What is the difference between urate and uric acid nephropathies?
Urate nephropathy: occurs w/ gout. MSU crystals deposit in DCT, collecting ducts, and interstitium -> tophus formation and scarring -> HTN, proteinuria, renal failure and chronic pyelonephritis
Uric acid nephropathy: occurs in pts. w/ leukemia / lymphoma receiving chemo. Large scale cell death -> increased uric acid formation -> precipitate in tubules -> ARF
Drugs for acute gout and what is contraindicated?
Steroids: Depo medrol, ACTH
Contraindicated: IV Colchicine, Allopurinol
What age group is most affected by pseudogout?
If suspected in >45 yoa work up for secondary causes
What are some secondary causes of pseudogout?
Hemochromatosis, HyperPTH, hypophosphatemia, hypomagnesemia, hypothyroid, gout, familial hypocalciuric hypercalcemia
Features useful in distinguishing pseudogout from gout
Pseudogout involves upper extremities early in disease course (late in gout)
Tenosynovitis is rare in pseudogout (common in gout)
CPPD deposits are radiodense (MSU is radiolucent)
pathophysiology of pseudogout
Abnormality in pyrophosphate (PPi) metabolism in chondrocytes -> PPi secretion -> complexes w/ Ca++ -> formation of CPPD crystals in cartilage -> coated w/ IgG, phagocytoses, inflammation
**PPi complex w/ Mg++ is soluble**
What is treatment for acute pseudogout and prophylaxis?
Acute: aspirate joint dry and inject corticosteroids
Dif between COX1 and COX2
COX1: Constitutively present in most tissues. Produces protective PGs -> homeostasis (stomach, kidney)
COX2: Induced by flammatory stimuli and cytokines
Action of aspirin
Irreversible COX inhibition (acetylation)
Inhibition of TXA2 synthesis -> inhibition of platelet aggregation
Platelet function returns to normal in 5-7 days
What is the role of renal prostaglandins? Effect of NSAID?
Renal prostaglandins: Maintain blood flow via vasodilation of afferent arterioles
NSAIDs block this action. Most concerning if CHF, CKD, hypovolemia
When is colchicine most effective in gout treatment?
First sign of flare up
2 tabs (1.2mg) immediately or w/in 12 hrs, then 1 tab (0.6 mg) one hour later. Repeat 1 tab q1-2 hrs until symptom resolution or diarrhea.
When are corticosteroids indicated for use in gout?
If NSAIDs are contraindicated
Can be given intra-articularly or PO
What is the goal in drug therapy to prevent gout?
Maintain uric acid at <6mg/dL
Most feared side effect of allopurinol
Allopurinol Hypersensitive Syndrome
Includes SJS and TEN - may be fatal
Stop use at first sign of rash
What is treatment for tumor lysis syndrome?
Rasburicase: recombinant form of uricase
What calcium supplement contains the highest level of elemental calcium?
What is daily calcium requirement by age group?
19-50: 1000 mg/day
>50, post-menopausal and osteoperotic patients: 1200-1500 mg/day
What drug is known to produce osteonecrosis of the jaw?
Bisphosphonates - usually in cancer patients
Risks: chemo, corticosteroids, poor oral hygiene
How are bisphosphonates dosed?
Daily, weekly, or monthly
Don't take w/ food, only w/ water. No food for 30-60 mins and remain upright after taking for 30-60 minutes.
What risks are associated with post-menopausal hormone replacement therapy?
Sulfasalazine side effects
Nephrotoxicity / stones
Yellow-orange skin and urine
What is Tofacitinib?
JAK kinase inhibitor: binds JAK-3 and inhibits IL production
Between biologic and synthetic DMARDS, which should be used first?
Always try synthetics before biologics
What is Abatacept?
Binds CD80/86 on APCs inhibiting costimulation of T-cells -> inhibiting Tcell activation
What is Tocilizumab?
Prevents signal transduction that leads to B and T cell infiltration
What is pannus?
Proliferative synovial tissue seen in RA. Invades and destroys joint and periarticular structures
What is Rheumatoid factor?
Rheumatoid factor: IgM that is anti-IgG (IgM binds IgG -> mac and synoviocyte activation and release of inflammatory mediators)
What is a marker other than RF factor that can be used in diagnosis of RA?
Anti - CCP Ab.
CCP = cyclic citrullated peptide: proteins w/ arginine residues that have been converted to citrulline
Less sensitive than RF, but more specific.
What happens to the lungs in RA?
Pleuritis -> effusion
Fibrosis is present in 20-40% of pts -> hypoxia
Rheumatoid nodules -> cavitating lesins
What is Felty's Syndrome?
RA + leukopenia + splenomegaly -> recurrent infections w/ S. aureus
Usually: HLA-DR4, +RF and +ANA
What happens to the kidneys in RA?
No direct implication, but patients may experience:
Disease secondary to medication use (NSAID -> renal insufficiency)
What is the most common nervous system complication seen in RA?
Carpal tunnel: compression of Median Nerve by thickened retinaculum
Major long-term complications of RA
Osteoporosis: corticosteroid use and cytokine induced osteoclast activation
Cardiovascular disease: due to systemic inflammation
Maliganancy: esp. lymphoma. Due to disease or treatment? Severe disease and MTX use may -> increased risk
What are the grades of sprains?
I: microscopic damage
II: stretch of ligament
III: disruption and instability
What is the minimum requirement for radiologic exam of a suspected skeletal injury?
2 plane projections taken at 90 deg from each other.
What patient populations are typically affected by the following femoral fractures: neck, intertrochanteric, subtrochanteric
Neck: older, osteoperotic
intertrochanteric: older, fall related injury
subtrochanteric: younger, trauma
What is the appearance of osteomyelitis on MRI?
T1: decreased marrow signal (dark)
T2: increased marrow signal (bright)
What is treatment for Lyme disease (septic arthritis)
Doxycycline (100 mg q12h) + Erythromycin (500mg q6h)
4-6 weeks of treatment
In septic arthritis, how long until irreversible damage is done to a joint?
72-96 hours - recognize and treat quickly!
What physical finding is suggestive of infection with Clostridium Perfringens?
Pungent smell and gas seen in tissue on radiograph
What infective organisms are seen in the following bites and what what treatments are called for:
Mammal (rodent / wild animal)
Domestic animal (dog/ cat)
Mammal: S. aureus, S. viridens: debridement + cephalosporins
Domestic animal: Pasturella multocida: penicillin + debridement
Human: Eikenella corrodens: debridement + amp / sulbactam