MuscSkCT - FA Patho p451 - 464 Flashcards
explain why estrogen is bone protective
estrogen blocks apoptosis in bone forming osteoblast and induces apoptosis in bone-resorbing osteoclast
what bone cell secretes acid and collagenases?
osteoclast
what cell is multinucleated and is derived from monocyte?
osteoclast
what bone path takes place in epiphysis?
giant cell tumors
what bone paths take place in metaphysis?
osteosarcoma (often around the knee), osteochondroma
what bone paths take place in diaphysis?
Ewing sarcoma, myeloma, osteoid osteoma, fibrous dysplasia
which bone path is associated with nighttime pain, central nidus, and pain released by aspirin?
osteoid osteoma
3 characteristics of Ewing sarcoma?
- anaplastic small blue cell malignant tumor 2. extremely aggressive with early metastases, but responsive to chemotherapy 3. “onion skin” periosteal reaction in bone
what population is most affected by Ewing sarcoma?
boys < 15 years old
what is the 2nd most common primary malignant tumor after multiple myeloma?
osteosarcoma (osteogenic sarcoma)
name 5 predisposing factors for osteosarcoma (osteogenic sarcoma)
- paget dz of bone 2. bone infarcts 3. radiation 4. familial retinoblastoma 5. Li Fraumeni syndrome (germline p53 mutation)
what is the age distribution on osteosarcoma?
biomodal distribution (10-20 yr old and more than 65)
what other malignancy has also bimodal distribution?
hodgkin (young adulthood and more than 55)
on x-ray, how will osteosarcoma look like?
codman triangle (from elevation of periosteum) or sunburst pattern on x-ray
what is the most common benign tumor?
osteochondroma
does osteochondroma transform to chondrosarcoma?
rarely yes
what is the characteristic of osteochondroma?
mature bone with cartilagionus (chondroid) cap
what bone tumor is characterized as soap bubble appearance on x-ray with multinucleated giant cells
giant cell tumor
what is the most common site of giant cell tumor?
epiphyseal end of long bone around knee (distal femur, prox tibia) - only 1 in this age group (20-40 yrs)
in paget dz of bone, hearing loss is due to
auditory foramen narrowing
name the 4 stages of paget dz of bone
- lytic (osteoclast) 2. mixed (osteoclast + osteoblast) 3. sclerotic (osteoblast) 4. quiescent (minimal osteoclast/osteoblast)
explain the pathophysio of the paget dz of bone
common, localized disorder of bone remodeling cause by inc in both osteoblastic and osteoclastic activity
what bone path is associated with mosaic pattern of woven and lamellar bone?
paget dz of bone
what is the most common site of osteonecrosis (avascular necrosis) and why?
femoral head (due to insufficiency of medial circumflex femoral artery)
name 7 causes for osteonecrosis
ASEPTIC 1. alcoholism 2. sickle cell 3. storage dz (Guacher) 4. exogenous steroid 5. Legg - Calve -Perthes 6. trauma 7. idiopathic 8. caisson (the bend)
what is another name for idiopathic cause of osteonecrosis?
Legg Calve Perthes disease
what is the pathophysio of achondroplasia?
(gain of function), constitutive activation of fibroblast growth factor receptor (FGFR3) inhibiting chondrocyte proliferation
mode of inheritance of achondroplasia?
autosomal dominant with full penetrance (homozygosity is lethal)
how is Laron syndrome diff from achondroplasia?
small genitalia, dec linear growth, everything small due to defective growth hormone receptor
treatment drugs for type 2 (senile) osteoporosis?
bisphosphonate, PTH analog (teriparatide), SERMs, calcitonin, denosumab
what is denosumab?
monoclonal antibody against RANKL
what bone path is associated with bone filling marrow space leading to pancytopenia and extramedullary hematopoiesis?
osteopetrosis (marble bone dz)
what is defective in osteopetrosis?
failure of normal bone resorption due to defective osteoclast leading to thickened, dense bones that are prone to fracture
what mutation is responsible for osteopetrosis?
mutations in carbonic anhydrase II impairing the ability of osteoclast to generate acidic environment necessary for bone resorption
what renal path will also have impaired carbonic anhydrase?
proximal (type2) urine pH
what is the treatment for osteopetrosis?
bone marrow transplant is curative as osteoclast is from monocytes
what path is associated with “bone-in-bone” appearance on x-ray?
osteopetrosis
what bone cell secretes acid and collagenases?
osteoclast
what cell is multinucleated and is derived from monocyte?
osteoclast
what is the diff btw osteoporosis and osteomalacia in terms of bone mineralization?
normal bone mineralization in osteoporosis abnormal bone minerailization in osteomalacia (rickets)
4 Rx causes for primary osteoporosis?
- long term steroid use 2. anticonvulsant 3. anticoagulants 4. thyroid replacement therapy
what symptoms/fractures can you get from osteoporosis?
Most commonly fractures from falls with fragile bones - hip, vertebra.
- vertebral compression fractures associated with acute back pain, loss of height, kyphosis 2. fractures of femoral neck 3. fractures of distal radius (Colles fractures)
2 bone paths with normal lab values?
- osteoporosis 2. osteopetrosis
what two bone paths will have the opposite lab values (Ca2+, PO43-, vs PTH/ALP?
osteomalacia/rickets and hypervitaminosis Osteomalacia - dec Ca2+, PO4, inc ALP,PTH Hypervitaminosis - inc Ca2+, PO4, dec ALP, PTH
2 causes for hypervitaminosis?
- oversupplementation 2. granulomatous dz (sarcoidosis)
explain how the lab values will be diff btw 1’ hyperparathyroidism vs 2’
1’: high PTH –> high Ca2+ –> low PO43-, high ALP 2’: high PO43- –> low Ca2+ –> high PTH, high ALP
In 2’ hyperparathyroidism, what causes high PO43- conc?
usually due to dec PO43- from ESRD
in 2’ hyperparathyroidism, what causes low serum Ca2+?
due to low activated vit D due to ESRD
MCP spared a. osteoarthris b. RA
a
RA which joint spared
DIP
pain improved with rest OA or RA
OA
TNF alpha inhibitors for RA List 3
etanercept (Enbrel), adalimumab (Humira), infliximab (Remicade), and certolizumab pegol (Cimzia)
what type of glucocorticoids would you give to osteoarthritis?
intra-articular
list two DMARDS for RA
Methotrexate Sulfasalzine hydroxychloroquine, leflunomide
most common fractures in osteoporosis type I?
femoral neck fracture, distal radius fracture
marker of osteoclast activity?
urinary OH-proline - breakdown product of collagen
Complications of Paget’s disease
inc blood flow from AV shunts –> high output heart failure and inc risk of ostogenic sarcoma
Paget’s assoc w. with what childhood infection?
Paramyxo virus
Which marker is abnormal in Paget’s
only an inc in ALP
Ewing sarcoma derived from what type of cells?
neuroectoderm poorly differentiated cells
RA association which HLA
HLA-DR4
what type of hypersensitivity is RA
type III IV
Heberden nodes in OA
He dips DIP
Bouchard nodes in OA
PIP and CMC
Pathology of rheumatoid nodules
fibrinoid necrosis with palisading histiocytes
most Specific marker for RA
anti-cyclic citrullinated peptide antibody
what is RF
IgM antibody against Fc portion of IgG
antibodies of sjogren
SSA SSB
what are SS-A and SS-B
ribonucleoproteins
Patient with Sjogren suddenly have unilateral enlargement of parotid gland
B cell lymphoma (MALT lymphoma)
Patient with acute onset monoarthritis, episodic pain
gout
what crystals 1. gout 2. pseudogout
gout: monosodium urate pseudogout: calcium pyrophoshate (rhomboid)
what type of joints do pseudogout affect
large joints, like the knee
what type of diuretics can cause gout
Loops and Thiazides - hyperuricemia
glycogen storage disease that cause gout
von gierke
negative birefringent what color
yellow parallel (BLUE parallel in pseudo) blue perpendicular
diseases associated with pseudogout
- hemachromatosis
- hyperparathyroid
- joint trauma
infectious arthritis in sexually active
n. gonorrheae
Infective Arthritis in older kids and adults
s. aureus
Gonococal arthrtis presentation
migratory arthritis with asymmetric pattern STD synovitis tenosynovitis dermatitis
Seronegative spondyloarthropathies what HLA
HLA-B27
sausage fingers pencil in a cup deformities on a Xray
psoriatic arthritis
vertebral body fusion
ankylosing spondylitis
see Aortic Regurg in which type of Seronegative arthritis
ankylosing spondylitis
conjunctivitis, urethritis, arthritis
Reactive arthritis reiter
cause of reactive arthritis
Post GI: shigella, salmonella, Yersinia, Campylo Chlymadia
Circinate balanitis
annular dermatitis of glan penis seen in reiter
keratoderma blennorrhagicum
hyperkeratotic vesicles in palms and soles reiter
SLE die with what type of kidney disease
nephritic DPGN
most sensitive SLE test
ANA
most specific SLE test
dsDNA, anti-smith
what is anti-Smith antibodies
Anti-snRNPs for splicing
drug induced SLE what antibodies
anti-histone
cause of drug-induced SLE
Methyldopa, Minocycline, Hydralazine, Isoniazid, Phenytoin, Sulfa drugs, Etanercept, Procainamide
antibodies in antiphospholipid syndrome
lupus anticog anticardiolipin anti-B2 glycoprotein
false positive VDRL
Viral infection (eg, EBV, hepatitis) Drugs (IV) Rheumatic fever Lupus and leprosy. Pregnancy
lupus anticog produce paradoxical prolongation of PT or aPTT
PTT
List the joint findings in osteoarthritis (6)
- Osteophytes (bone spurs) 2. joint space narrowing 3. subchondral sclerosis and cysts 4. eburnation (polished ivory like appearance of bone) 5. Heberden nodes 6. Bouchard nodes Synovial fluid non-inflammatory (WBC
this marker in SLE indicate poor prognosis
anti-dsDNA
MCP spared a. osteoarthris b. RA
osteoarthritis
RA + pneumoconiosis
Caplan syndrome
A 40 yo female comes in with a Hx of dyspnea especially after climbing stairs. HR and pulse are normal. After doing pulmonary function test, results show an elevated FEV1/FVC ratio. She also has a slight facial droop that has been worsening over the months. What pathology is associated with these symptoms, and what findings are prominent on imaging?
The pt has Sarcoidosis and hilar nodes are prominent on CXR known as potato sac lymph adenopathy bilaterally. The facial droop is due to Bell’s palsy.
A physician orders a biopsy for an African descent patient with positive HX for Sarcoidosis. What will be found in the biopsy (appearance and inclusions)?
Epithelioid granulomas containing Asteroid and Schuamann bodies
A physican orders lab test for a 40 yo female with interstitial fibrosis suspected of Sarcoidosis. What metabolites will be elevated and the mechanism behind the pathology
Hypercalcemia. Sarcoidosis causes increased activation 1 alpha hydroxylase in the kidney. This mediates Vitamin D activation and leads to increased Ca reabsorption
A 60 yo female comes into the ER complaining of severe pain in her hips. She previously stated that she has been having intermittent pain in her temples What disease is she affected by at the moment? Which lab results will be found?
Polymyalgia Rheumatica –> Assoc with GCA. Lab reults will show elevated ESR, CRP.
A 40 yo female comes to her family physician complaining of pain and stiffness in her muscles. She also feels lethargic during the day, and is having trouble sleeping at night. What Dx do the physician make and what does he prescribe?
Fibromyalgia TX with SNRI/TCA and anti-convulsants and regular exercise
A patients come in a malar rash and redness on her hands. The physician also notices that the patient’s hands look roughed up as if she has been working outside with her hands. What is the Dx and TX?
Dermatomyositis with perimysial inflammation from CD4 Th cells. Tx with corticosteroids + MTX
Immunopathologically how does Polymyositis differ from dermatomyositis?
Polymyositis- Cd8 +CTL induced endomysial inflammation Dermatomyositis - CD4+ Th cells induced permysial inflammation
A 40 yo female comes in with a Hx of dyspnea especially after climbing stairs, and has lost 10 lbs of weight in the last 3 months. HR and pulse are normal. She also feels tired easily and feels weakness in washing dishes in the morning and prefers to do them at night time. What pathology is associated with these symptoms, and what underlying mechanism is associated with it?
Patient has Lambert Eaton syndrome where the Abs are destroying her presynaptic Ca Ch and decrease ACh release in the NMJ. LE syndrome is associated with Small CC of the lung which explains the dyspnea and cachexia
How does Myasthenia Gravis differ from LE with regards to muscle movement? Why?
Muscle weakness worsens as the day progresses b/c Abs are against the AcH receptor. As the day ends the ACh receptors decrease which causes increased weakness later.
A 45 yo female comes into her physician and complains of increased tightness and puffiness in her skin. She also shows that fingertips around her nails feel rougher than usual. What is the physician worried about after confirming his DX with these lab results to be positive?
The patient is positive for anti topoisomerase I Ab (SCl-70) as and has Diffuse systemic Scleroderma. These patients have a high mortality rate with renal and pulmonary sclerosis.
Name the findings in Limited Scleroderma (5 S/S) and the Ab associated with the path?
Limited Scleroderma is associated with anti centromere AB CREST syndrome 1) Calcinosis 2) Raynaud’s phenomenon 3) Esophageal dysmotility 4) Sclerodactyly 5) Telengectasia
Genetic issue with Ewing sarcoma?
t(11;12) translocation causing fusion protein EWS-FLI 1
Rx associated with Osteoporotic fractures?
- anticonvulsants that (+) p450 (phenobarbital, phenytoin, carbamazepine) - inc Vit D catabolism
- Aromatase (-)’rs/Hydroxyprogesterone - Dec estrogen
- GnRH (+)’r - dec testosterone/estrogens
- PPI - dec Ca absorption
- Glucocorticoids,
- Unfractionated heparin,
- Thiazolidindiones - dec bone formation
bony mass with radiolucent core, nighttime pain, cental nidus
osteoid osteoma
Causes of uric acid overproduction
Lesch Nyhan, PRPP excess, inc cell turnover (tumor lysis syndrome), von Gierke disease, dec G6Pase
which gout rx works by (-) microtubule polymerization?
colchicine
locations of tophus formation?
external ear, olecranon bursa, achilles tendon
Rx that inc uric acid formation
Pyrazinamide, Thiazides, Furosemide, Niacin, Cyclosporin
rhomboid crystals that are birefrigent?
calcium pyrophosphate deposition disease (pseudo gout)
invasion of exocrine glands by lymphocytes?
sjogrens (why has dry eyes and mouth)
migratory arthritis seen with infectious arthritis and what other illness?
Lyme disease
Decrease of what immune components with SLE?
C3, C4, CH50 - due to immune complex formation
associated with anti U1 RNP antibodies
mixed CT disease (speckled ANA)
increased serum ACE levels and CD4+/CD*+ ration in bronchoalveolar lavage fluid?
Sarcoidosis
why is there hypercalcemia with sarcoidosis/.
due to inc alpha hydroxylase mediated vitamin D (+)’n in macrophages
why can polymyalgia rheumatica present with pain in shoulders and hips, as well as temporal pain?
associated with temporal arteritis (giant cell)
markers with polymyositis/dermatomyosititis?
Inc CK, pos for ANA, anti-Jo1, anti-SRP, and anti-Mi2
red, sometimes scaly, papules that erupt on any of the finger joints, made worse by sunlight exposure?
Gottron papules of Dermatomyositis
What is Raynaud’s?
dec blood flow to the skin due to arteriolar vasospasm in response to cold or stress, often in fingers and toes
How to treat Raynaud’s?
CCB
triad of autoimmunity + noninflammatory vasculopathy + collagen deposition with fibrosis?
Scleroderma
