Musculo/Derm 3 Flashcards
What is Parathyroid hormone (PTH)?
A hormone that increases blood calcium levels by promoting phosphate excretion and stimulating osteoblast activity.
What is the treatment for Rickets and Osteomalacia?
Vitamin D and Ca supplementation.
What is the best indicator for Vitamin D status? Why?
Serum 25-OH Vit D
It has a long half-life and liver production is not regulated by PTH.
What is the storage form for Vitamin D?
25-OH Vitamin D.
What is Paget’s Disease also called?
Osteitis Deformans.
Is Paget’s disease a focal or widespread disorder?
Focal.
Paget’s Disease is common in what age group?
Older patients.
What is the mechanism of Paget’s Disease of the bone?
Excessive bone remodeling, believed to be due to abnormal osteoclasts.
What are the 3 phases of Paget’s disease?
Initial (Osteolytic), Mixed (Osteolytic-osteoblastic), Final (Osteosclerotic).
What occurs in the Osteosclerotic phase of Paget’s disease?
Bone formation dominates and hypervascularity of bone occurs.
What is the hallmark of Bone morphology in Paget’s disease?
Mosaic pattern of lamellar bone.
What is the most common complication of Paget’s disease?
Chalkstick fracture.
What are 7 clinical features of Paget’s disease?
Chalkstick fracture, Bone pain, Bowing of legs, Enlarged skull (increased hat size), Cranial nerve compression, Radiculopathy at spine, Erythema over affected bone area due to hypervascularity.
What is a lab finding in Paget’s disease?
Increased bone alkaline phosphatase.
Paget’s disease leads to an increased risk for?
Osteosarcoma.
What are 2 treatments for Paget’s disease?
Calcitonin, Bisphosphonates.
Osteitis Fibrosa Cystica is a classic bone disease of?
Hyperparathyroidism.
Parathyroid adenoma leads to what 3 lab findings?
↑ PTH, Hypercalcemia, ↓ Phosphate.
What are 2 X-ray findings in Osteitis Fibrosa Cystica?
-Subperiosteal bone resorption: irregular or indented edges to bone
-Brown tumors: collection of giant osteoclasts in bone, appears as black spaces.
What is Renal Osteodystrophy? What does this include?
Bone abnormalities seen in renal failure: Osteitis Fibrosa Cystica, Rickets/osteomalacia, Osteopenia/osteoporosis, Growth retardation, Bone pain, Fractures.
What are 4 lab findings in Renal Osteodystrophy?
↓ Calcium, ↓ Vitamin D (active form), ↑ PTH, ↑ Phosphate.
What are 4 bone disorders that will have normal Ca2+ and PTH?
Osteoporosis, Osteopetrosis, Paget Disease, Bone Tumors.
Does Osteoporosis affect Trabecular or Cortical bone more?
Trabecular (high surface area).
What are 3 areas with high trabecular bone content?
Spine, Head of femur (hip), Wrist (distal radius).
Osteoporosis is common in what demographic?
Elderly white women.
When does peak bone mass occur?
Young adulthood.
Why are men less likely to have osteoporosis?
They achieve higher peak bone mass.
What is a standard recommendation to prevent Osteoporosis?
Weight bearing activity → ↑ bone mass.
What are Calcium, PTH, Alkaline phosphatase findings in Osteoporosis?
All normal.
What are Secondary Causes of Osteoporosis?
-Glucocorticoids: increase bone resorption, decrease bone formation
-Alcohol
-Smoking: accelerates bone loss
-Phenobarbital, Phenytoin, Carbamazepine
-Unfractionated Heparin (long term)
-Thyroid hormone Replacement: Too high dose → iatrogenic hyperthyroidism
-Hyperthyroidism
-Hyperparathyroidism
-Multiple myeloma
-Malabsorption syndromes (poor absorption of Ca2+/Vit D deficiency).
What is the underlying mechanism of Phenobarbital/Phenytoin causing Osteoporosis?
P450 enzymes inducer → Increases breakdown of vitamin D → Less calcium → increased PTH → bone loss.
What test should be performed for a patient on thyroid replacement therapy to minimize progression of bone loss?
TSH (if TSH is low then need to lower dose).
What are 2 ways to diagnose Osteoporosis?
-Fragility fracture
-T-score of 2.5 or lower on DXA.
What screening test is used for Osteoporosis? Who is this recommended for?
-Dual-energy X-ray absorptiometry (DXA) → T score
-Women >65 y/o.
How is a T score obtained in Dual-energy X-ray absorptiometry (DXA)?
Compare patient BMD vs. healthy 30 year old BMD (-1.0 or higher is normal).
What are 2 classic areas for fractures in a patient with Osteoporosis?
-Hip
-Spine: often occur slowly over time → loss of height, kyphosis.
What are 4 lifestyle modifications for Osteoporosis Therapy?
Smoking cessation, Avoid heavy alcohol use, Weight bearing exercise, Ca2+ and vitamin D supplementation.
What is the mechanism of Bisphosphonates?
Pyrophosphate analog → binds calcium, accumulate in bone → taken up by osteoclasts → inhibits osteoclasts.
What are adverse effects of Oral Bisphosphonates?
Upper GI upset: Reflux, esophagitis, esophageal ulcers.
How should Oral Bisphosphonates be taken? How often are they usually taken?
-Take with water on empty stomach
-Remain upright for 30 minutes
-Often taken weekly.
What are adverse effects of IV Bisphosphonates? This can be treated with?
Flu-like symptoms (low grade fever, myalgias) → ibuprofen, acetaminophen.
How often is IV Bisphosphonates administered?
3-months to annually (Long dosing intervals).
What are 2 uncommon Adverse effects of Bisphosphonates?
Atypical femur fractures, Osteonecrosis of the jaw (avascular necrosis).
What are Atypical femur fractures?
-Below less trochanter
-Diaphyseal
-No or minimal trauma.
What is Teriparatide? How is it used?
Recombinant human PTH, increases osteoblast bone formation
Low dose daily SQ injection.
What are 2 adverse effects of Teriparatide?
Brief rise in serum calcium, Theoretical risk of osteosarcoma.
What form of Calcitonin is used in humans?
Salmon calcitonin.
What is the mechanism of Denosumab?
Monoclonal RANK-L antibody → block osteoclast activation.
Which is more common: Bone metastasis or Primary bone tumor?
Bone metastasis.
Where in the bone are Bone metastasis most common?
Diaphysis.
What are the 2 types of Metastatic bone lesion? What cancer are they associated with?
Osteoclastic lesion: multiple myeloma, Osteoblastic lesion: Prostate carcinoma.
Primary Bone Tumors often occur in?
Children/young adults.
Primary Bone Tumors are more common in [M/W]?
Men.
Primary Bone Tumors usually involve what bones?
Long bones, especially at knees.
Primary Bone Tumors may cause what 2 symptoms?
Bone pain, Pathologic fractures (proximal femur and humerus are most frequent sites).
What is Osteoid Osteoma? Where do they commonly occur?
Benign small (<2cm) tumor of bone of young men (tumor of osteoblasts)
Occur in appendicular skeleton.
Is Osteoid Osteoma responsive to NSAIDs or aspirin?
Yes.
Osteoid Osteoma presents as?
Bone pain at night.
Where in the bone does Osteoid Osteoma occur? How does it appear histologically?
Surface of cortex of diaphysis
Osteoid core with rim of woven bone.
How does Osteoid Osteoma appear on X-ray?
Bump on the edge of the bone with central osteoid core.
Osteoblastoma often involves what bone?
Spine.
Is pain from Osteoblastoma responsive to NSAIDs or aspirin?
No.
What is the gene mutation in Gardner’s Syndrome?
APC gene mutation.
Gardner’s Syndrome is a variant of?
Familial Adenomatous Polyposis.
What bone manifestation often occurs in Gardner’s syndrome? Where do they usually occur?
Osteomas, usually in skull or mandible.
What is the most common primary bone tumor?
Osteosarcoma.
Osteosarcoma is a malignant bone tumor of?
Osteoblasts.
What is the age distribution of Osteosarcoma?
Bimodal: 75% young adults, 25% older adults (i.e. Paget’s).
Histopathology of Osteosarcoma?
Pleomorphic cells with irregular osteoid formation (pink).
What is the clinical presentation of Osteosarcoma? Where do they commonly occur?
Painful, enlarging mass on bone usually in metaphysis of long bones
50% occur at knee (distal femur, proximal tibia).
What are 2 classic X-ray findings in Osteosarcoma?
Codman triangle: Tumor breaks through cortex and lifts periosteum, Sunburst sign.
Osteosarcoma is associated with what conditions?
Pagets, Prior radiation, Familial retinoblastoma (Rb gene mutation), Li Fraumeni syndrome (p53 tumor suppressor gene).
What is the treatment for Osteosarcoma?
Always treated with chemotherapy prior to surgery (poor prognosis with surgery alone)
“En bloc” resection: Removal of entire tumor in one piece with a layer of healthy tissue.
What is Ewing Sarcoma?
Malignant bone tumor of undifferentiated neuroectoderm cells.
Ewing Sarcoma usually presents during?
Childhood (80% <20 y/o).
Ewing Sarcoma occurs in what part of the bone? Most commonly which bone?
Diaphysis of long bones, most commonly femur.
Is Ewing Sarcoma aggressive?
Yes.
What is the clinical presentation of Ewing Sarcoma? It can be confused with?
Fever, leukocytosis, painful growing mass over bone
Osteomyelitis.
How to differentiate Ewing Sarcoma and Osteomyelitis?
Blood cultures and tumor aspiration: sterile.
What is a classic x-ray finding of Ewing Sarcoma?
Onion skin (splitting/thickening of cortex).
Histopathology of Ewing Sarcoma?
Sheets of small round blue cells.
Ewing Sarcoma is associated with what genetic mutation?
Genetic translocation: Fusion of EWSR1 gene(22) to FLI1 gene (11).
Giant Cell tumor is also called?
Osteoclastoma.
Is Giant Cell tumor malignant?
No, but locally aggressive.
Giant Cell tumor usually occurs in what part of the bone? Where is it most common?
Epiphysis, most commonly at knee.
The stromal tumor cells in Osteoclastoma express high levels of?
RANK-L → drives osteoclast activity.
Giant Cell tumor Histopathology?
Multi-nucleated giant osteoclasts.
What is Osteochondroma?
Benign cartilage forming tumor.
When do Osteochondroma occur? Are they more common in M/W?
Early adulthood, men.
Osteochondroma on X-ray will present as?
Cartilage-capped bone spur.
Osteochondroma arise from the?
Growth plate (metaphysis).
Osteochondroma stop growing with?
Growth plate closure.
Osteochondroma is treated with?
Simple excision.
What is Fibrous Dysplasia? Where does it occur in the bone?
Benign tumor, fibrous tissue replaces bone
Occurs in medulla/diaphysis.
What is a histopathologic finding of Fibrous Dysplasia?
“Chinese character” Trabeculae of woven bone.
What is an X-ray finding of Fibrous Dysplasia?
Lytic lesion in diaphysis.
What are Simple bone cysts? Where are they common?
Fluid-filled spaces with fibrous lining
Proximal humerus and femur.
What is the treatment for Simple bone cysts?
Observation with serial X-rays, often spontaneously improves.
Where in the bone are Simple bone cysts found?
In metaphysis.
Chondroma occurs in what bone?
Small bones of hands and feet.
Chondromas in the medullary cavity are called?
Endochondromas.
Chondromas on the surface of bone are called?
Juxtacortical chondromas.
Where does Chondrosarcoma often occur? Where in the bone?
Occur centrally (pelvis, shoulder, ribs)
Medulla.
Calcium and PTH levels in bone tumor?
Normal.
Bone mass in the skull with Eosinophils present suggests?
Langerhans Cell Histiocytosis- Eosinophilic granuloma.
Cell within Eosinophilic granuloma express what 3 markers?
CD1a, S100, CD207.
What is the most common type of arthritis?
Osteoarthritis.
Articular cartilage is composed of what type of collagen?
Type II.
What is a major component of synovial fluid?
Hyaluronic acid.
What leads to the development of Osteoarthritis?
Hyaline cartilage breakdown, Abnormal chondrocytes: proliferate in OA but inadequate repair → eventually die and expose bone.
Osteoarthritis present with [low/high] WBC in synovial fluid?
Low (non-inflammatory arthritis).
What are 4 X-ray findings seen in Osteoarthritis?
Joint space narrowing, Subchondral sclerosis, Osteophytes (bone spurs), Subchondral cyst.
What is the main component of synovial fluid?
Hyaluronic acid
What leads to the development of Osteoarthritis?
Hyaline cartilage breakdown
Abnormal chondrocytes: proliferate in OA but inadequate repair → eventually die and expose bone
Osteoarthritis presents with [low/high] WBC in synovial fluid.
low (“non inflammatory arthritis”)
What are 4 X-ray findings seen in Osteoarthritis?
Joint space narrowing
Subchondral sclerosis
Osteophytes (bone spurs)
Subchondral cyst
What are Osteophytes?
Bone spurs, thickening of subchondral bone at joint margins
How are Subchondral cysts formed?
Bone cracks → synovial fluid accumulation
Osteoarthritis often involves what joints?
Both knees: medial knee affected more
DIP and PIP joints, 1st Carpometacarpal joint
Facet joints in lower cervical and lumbar spine
Hip
Where do Heberden’s and Bouchard’s nodes occur?
Heberden’s: DIP
Bouchard’s: PIP
Nodal osteoarthritis is believed to be caused by?
osteophytes
What are 3 symptoms of Osteoarthritis?
Joint pain
Stiffness
Restricted motion
Joint pain in Osteoarthritis improves with [rest/activity].
rest
Joint pain in Osteoarthritis is usually worst at?
end of day for weight bearing joint
What are 4 risk factors for Osteoarthritis? Which is modifiable?
Old age
Female
Obesity: modifiable
Joint injuries
What is the treatment for Osteoarthritis?
Exercise
Weight loss
Pain control: Acetaminophen, NSAIDs
Intraarticular glucocorticoid injection: controversial
Surgery
What are 5 differences between Rheumatoid arthritis and Osteoarthritis?
RA:
Women 40-50
High synovial WBC
Joint pain improves with activity
Morning stiffness
Systemic complications: uveitis, serositis, Baker’s cyst
What is the clinical presentation of Septic Arthritis?
Acute onset
Swelling and pain usually of single joint
Fever, chills, sweats
What are 3 pathogens commonly responsible for Septic arthritis?
S. aureus
S. pneumoniae
Neisseria gonorrhoeae
Patient with Acute monoarthritis must consider what 3 conditions?
Septic arthritis, gout, pseudogout
Arthritis in Hemochromatosis commonly affects what joint?
MCP joint
What is a key lab finding of Hemochromatosis?
high serum ferritin (iron overload disorder)
What is gout? What are the symptoms and what is the mechanism?
Monosodium uric acid deposition in joints
Crystals phagocytosed → trigger inflammatory response → severe joint pain, swelling warmth
Gout most commonly involves what joint? It can also occur in?
1st MTP joint
Knee
What are 3 factors required for gout development?
Hyperuricemia + cool temperatures + genes
What is a Tophi?
uric acid collections in connective tissue (ears, tendons, bursa), not painful
Chronic Tophaceous Gout is seen with?
long standing gout
Chronic gout can lead to what renal condition? What does this lead to?
Urate nephropathy: Uric acid crystals in urine → uric acid stones → chronic renal failure
What is primary gout? What is it associated with?
Gout not due to any other disease or medication
Associated with under excretion of uric acid
Uric Acid Excretion is mostly through?
the kidneys
What leads to a decrease in uric acid excretion? What are 3 examples?
Reduction in GFR: renal failures, volume depletion, diuretics
What are 2 common purine sources that can cause gout attack?
Red meat/Seafood
Trauma/surgery (tissue breakdown)
What are the 2 mechanisms by which Alcohol can trigger gout?
Metabolism consumes ATP → uric acid
Lactic acid from alcohol metabolism increases Urate transporter-1 (URAT1) activity → Increased reabsorption of uric acid
Gout attacks are more common among what type of patients?
Obese males
Classic case of gout presents as?
an obese male after steak dinner with heavy alcohol consumption
What enzyme is defective in Lesch Nyhan Syndrome? What is the inheritance pattern?
HGPRT, X-linked
HGPRT is an enzyme involved in?
purine salvage pathway
Clinical presentation of Lesch-Nyhan syndrome?
Excess uric acid production (“juvenile gout”)
Neurologic impairment
Hypotonia, chorea
Self mutilating behavior
What enzyme deficiency is seen in Von Gierke’s Disease?
Glucose-6-phosphatase deficiency (Glycogen Storage Disease Type I)
What is the clinical presentation of Von Gierke’s Disease?
Severe hypoglycemia between meals → Seizures, Lactic acidosis
Lactic acidosis increases URAT1 activity → increased reabsorption
How to diagnose gout?
Arthrocentesis → polarized light microscopy, high WBC count
How do gout crystals appear under polarized light microscopy?
“Negatively birefringent”
Yellow when parallel to axis of the polarization
Blue when perpendicular to polarization axis
What are 3 drugs used for acute Gout attacks?
NSAIDs
Glucocorticoids
Colchicine
What are 3 drugs used for Gout prevention?
Xanthine oxidase inhibitors (allopurinol, febuxostat)
Pegloticase
Probenecid
What is the mechanism of Colchicine?
Binds to tubulin → prevents polymerization of microtubules (microtubule inhibitor)
Inhibits WBC migration and phagocytosis
What is the mechanisms of Allopurinol and Febuxostat?
Xanthine Oxidase inhibitor:
Allopurinol: competitive
Febuxostat: non-competitive
What are 2 clinical uses for Xanthine Oxidase inhibitors?
Gout
Prevent Tumor lysis syndrome
For gout treatment, Xanthine Oxidase Inhibitors are initiated together with what drug? Why?
NSAIDs/Colchicine
Abrupt change in serum uric acid levels may precipitate a gout attack
Allopurinol and Febuxostat can increase toxicity of what 2 drugs?
Azathioprine and 6-MP
What is the mechanism of Pegloticase? What is the route of administration?
Recombinant uric acid oxidase (degrades uric acid) attached to polyethylene glycol which prolongs half-life
IV
Pegloticase converts uric acid into?
allantoin (excreted by kidneys)
What is the mechanism of Rasburicase?
Recombinant uricase (converts uric acid to allantoin)
What is the clinical use for Rasburicase?
Tumor lysis syndrome
What are 4 lab findings seen in Tumor Lysis Syndrome?
Hyperkalemia → arrhythmias
Hyperphosphatemia → hypocalcemia
Hyperuricemia → uric acid nephropathy/acute renal failure
What are 2 effects of Probenecid? What is an Adverse effect?
Blocks proximal tubules reabsorption of uric acid (uricosuric)
Blocks secretion of penicillin
A/E: uric acid kidney stones
What is the effect of high dose vs low dose aspirin in gout?
High dose: inhibits secretion and reabsorption of uric acid (uricosuric)
Low dose: inhibits secretion of uric acid → hyperuricemia
Is Low dose aspirin use for pain control in gout?
No
What is the cause of Calcium Pyrophosphate Deposition Disease?
unknown
Calcium Pyrophosphate Deposition Disease occurs in [younger/older] patients.
older (average 72 y/o)
What are 3 clinical patterns of Calcium Pyrophosphate Deposition Disease?
Asymptomatic (discovered on imaging)
Acute arthritis (similar to gout)
Chronic joint disease (similar to OA)
What is a X-ray finding seen in Asymptomatic Calcium Pyrophosphate Deposition Disease?
Chondrocalcinosis: calcification of hyaline cartilage
What is pseudogout? What joint is commonly involved?
Acute attack of arthritis seen in Calcium Pyrophosphate Deposition Disease
50% of cases involved knees
Pseudogout is provoked by [3]. May flares are reported after?
Trauma, surgery, medical illness
Parathyroidectomy
Pseudogout visualized under Polarized Light Microscopy will appear as?
Rhomboid crystals, positively birefringent
Blue when parallel to light (yellow for gout)
What is the treatment for acute pseudogout attack?
NSAIDs, colchicine, or glucocorticoids
