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31 Cards in this Set
- Front
- Back
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What does this patient have?
A 30-year-old woman came in after several weeks of fever and fatigue. She also has shortness of breath and a cough. Exam shows tender nodules on the lower extremities. A chest X-ray shows hilar adenopathy. Lab studies reveal an erythrocyte sedimentation rate (ESR) of 55 mm/hr and a serum calcium of 11.3mg/dl (normal 8.5-10.4). Angiotensin converting enzyme is elevated. |
This patient has sarcoidosis. The mechanism of hypercalcemia in sarcoidosis is the conversion of 25 vitamin D to 1,25 vitamin D at extrarenal sites by a 1 alpha hydroxylase present in granulomatous tissue. The elevated calcitriol stimulates osteoclastic bone resorption as well as intestinal absorption of calcium. Increased and unregulated production of calcitriol can occur in other granulomatous disorders (Wegener’s, tuberculosis and in lymphoproliferative diseases such as Hodgkin’s). The rate of endogenous 1,25 vitamin D production in sarcoid granulomas is sensitive to inhibition by steroids, this is not the case for renal 1-alpha hydroxylase. Of course, zolendronate and other second and third generation intravenous bisphosphonates would also lower serum calcium as the primary mechanism for hypercalcemia in patients with calcitriol excess is excessive osteoclastic bone resorption, and bisphosphonates reduce osteoclast number and activity.
Treat with glucocorticoids! |
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A 65-year-old man has a cough. Chest X-ray reveals a 3 cm pulmonary nodule and an enlarged hilum. History reveals a 70 pack year history of smoking. Lab reveals a serum calcium of 11.9mg/dl (normal 8.5-10.2).
Further evaluation of the patient’s hypercalcemia is most likely to show which marker elevated in the blood? |
This patient is likely to have humoral hypercalcemia of malignancy (HHM) resulting from the production of PTH related protein (PTHrP). The most common cancers that produce PTHrP are squamous cell cancers, primarily of the lung but also head and neck, esophagus, skin, vulva, and cervix. PTHrP, which shares significant homology with PTH in the N-terminus, is the principal mediator of humoral hypercalcemia of malignancy. PTH levels are normal or reduced in HHM.
HHM differs from primary hyperparathyroidism (HPT) in that 1,25 vitamin D levels are not elevated as in HPT. In HPT osteoblastic bone formation is increased and is coupled to bone resorption. In HHM, osteoblastic bone formation is reduced and thus uncoupled to the ongoing increased osteoclastic bone resorption. Production of a humoral factor, PTHrP, occurs in at least 80% of all malignancies that are associated with hypercalcemia. In malignancy, although widespread skeletal metastases can result in hypercalcemia the majority of patients with malignancy and hypercalcemia will have HHM. Some lymphomas can produce calcitriol ectopically, so this activated form of vitamin D is also considered a mediator of humoral hypercalcemia. Treat with intravenous zolendronate (bisphosphonate) |
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A 60-year-old woman came in with bone pain in the pelvis and lower extremities. She has difficulty rising from a chair without using her arms. A DXA reveals a lumbar spine T-score of -3.5. Lab results include a 25 hydroxyvitamin D level of 5 ng/ml. She has a history of grand mal seizures and is on anticonvulsant therapy.. She was started on alendronate 5 years ago after a DXA. She has been on 5 mg of prednisone for 1 year for a rheumatic disorder. Additional lab testing is ordered in this patient including 1, 25 OH vitamin D, alkaline phosphatase and PTH. Which of the following would be the most characteristic X-ray finding in this patient?
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The X-ray finding characteristic in adults with osteomalacia are radiolucent lines caller Looser zones. Often called pseudofractures or Milkman lines (after Dr. Milkman, not the delivery guy!), these are areas of cortical lucency with surrounding sclerosis. They are usually perpendicular to the cortex and are often seen in the femur, pubis and ischium, and likely represent enlargement of vascular canals through bone. Anterior wedge fractures may be seen but are not diagnostic as are Loosers zones. Bowed long bones and widening of the epiphysis are seen in children with rickets which are the result of abnormalities during growth when the growth plates are open.
Transverse lucent lines in the femur and pelvis |
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Disease of short limbs. Head and torso are normal size. Dwarfism.
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Achondroplasia
Without, cartilage, growth Activating mutation in FGFR3 which inhibits chondrocyte proliferation Normal lifespan and fertility |
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Disease of loss of trabecular bone
Normal bone mineralization and labs |
Osteoporosis: can lead to verteral compression fractures- acute back pain, loss of height, kyphosis
Type 1 = postmenopausal femoral neck fracture, distal radius/ Colle's fractures Type 2 = Senile Prevented by exercise and diet before 30 |
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Treatments for Osteoporosis:
Bisphosphonate Denosumab Teriparatide Raloxifene |
Bisphosphonate:
cause osteoclast apoptosis Alendronate (Fosfamax) Denosumab Den = dense os = bone umab = human monoclonal Ab Ab against RANK-ligand (antiosteoclastic) Teriparatide: intermittent PTH injections increases both blasts and clasts, but blasts more Raloxifene Selective Estrogen Receptor Modulator pro-estrogen |
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Are anticonvulsants (AEDs) pro or anti bone formation?
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Contraindicated for osteoporosis
AEDs are metabolized in liver by CYP P450, which upregulates this enzyme CY P450 (24) will inactivate 25hydroxy cholecalciferol into the inactive 24,25 dihydroxy cholecalciferol |
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Disease of increased bone density with normal labs
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Osteopetrosis
Failure of normal bone resorption Increased density can close the marrow space leading to anemia, thrmbocytopenia Genetic deficiency in carbonic anhydrase. Acidic environment is required to resorb calcium by osteoclasts Think of pouring coke down drain to remove calcium Cranial nerve imingment |
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Disease of defective bone mineralization:
Low serum Ca, Low Phosphagte, increased PTH |
Osteomalaica / Rickets
Osteoid is not mineralized Lack of vitamin D VitD acts on intestine to increase calcium and phosphate absorption. Acts on kidneys to increase Ca and P reabsorption. Acts on Bone to resorb calcium |
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Disease of increased osteoblastic and osteoclastic activity.
Patients with increased hat size. |
Paget's Disease
Triphasic: osteoclastic (more resorption than formation) matched (increased both, but matched formation) osteoblastic (osteoclasts burnout and the osteoblasts take over) Increased ALP, (Alkalkine phosphatase creates alkaline environment for calcium mineralization) Complications: -High-output cardiac falure due to formation of AV-shults -Osteosarcoma (normally seen in teens) Signs? Increased hat size |
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Polyostotic Fibrous Dysplasia
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Bone is replaced by fibroblasts, collagen and irregular bony trabeculae
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Skeletal changes due to chronic renal failure
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Renal Osteodystrophy
Renal failure leads to Phosphate retention. Hyperphosphatemia leads to secondary hyperparathyroidism High phosphate levels reduce activity of alpha-1-hydroxylase so 25-vitamin-D is not converted to active form (1,25) High PTH leads to osteoclast activity increase |
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Bone tumor of face
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Osteoma
Cotext tumor of face and skull Seen in Gardner's Syndrome (Familial Adematous Polyposis) |
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Bone tumor with osteoid center and surrounding reactive bone
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Osteoid Osteoma
<2cm young adults <25yo bone pain is relieved by aspirin Cortex of long bones in diaphysis Osteoblastoma is in the vertebrae is is not relieved by aspirin |
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Benign bone tumor with cartilage cap
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Osteochondroma
Lateral projection of bone from the metaphysis (growth plate) *The cartilage can transform into malignant chondrosarcoma |
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Malignant bone tumor of osteoblasts
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Osteosarcoma
Peak incidence in teenagers (Familial retinoblastoma) and in elderly (Paget's disease and radiation) ***Codman's Triangle where the periosteum is elevated above bone. Sunburst pattern on xrax knee area: distal femur or proximal tibia |
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Only bone tumor of the epiphysis
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Giant cell tumor
Soap bubble appearance on x-ray typically knee area |
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Malignant bone tumor of neuroectodermal cells
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Ewing Sarcoma
11:22 translocation Diaphysis of long bones in male children Within medullary cavity resultin in onion skin appearance in diaphysis |
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Benign cartilage tumor in hand
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Chondroma
benign tumor in hands and feet within medullary space |
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Malignant cartilage tumor in pelvis
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Chondrosarcoma
malignant tumor in pelvis and central skeleton in the medullary space |
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Disease with a hallmark of pannus formation in the synovium
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RA
MCP and PIP involvement but not DIP involvment (that's osteoarthritis) Characterized by type III hypersensitivity (autoimmune) Rheumatoid factor = antibody to Fc portion of IgG |
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Is there a genetic component to Rheumatoid Arthritis?
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Yes. HLA-DR4 (B1)
anti-IgG Fc portion (rheumatoid factor) anti-CCP antibody is less sensitive but more specific |
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How is RA different from OA?
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RA is autoimmune, so there will be morning stiffness. Symmetric joint involvement. Systemic symptoms: fever, fatigue, pleuritis, pericarditis
OA has inflammation upon use |
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What are the disease modifying drugs (DMARDs) used to treat RA?
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Methotrexate: folate synthesis inhibitor
Hydroxychloroquine: antimalarial § Leflunomide □ Pyrimidine synthesis inhibitor ® Inhibits dihydroorotate dehydrogenase ® Prohibits expansion of activated lymphocytes ◊ de novo synthesis of the pyrimidine ribonucleotide uridine monophosphate (rUMP) |
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What are the biologic drugs used to treat RA?
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TNF-alpha inhibitors
Etanercept = Enbrel this is a decoy receptor Infliximab Adalimumab Anakinra = IL-1 inhibitor |
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A swedish patient has dry eyes and dry mouth... what disease might they have?
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Sjogren's Syndrome
Xerophthalmia = dry eyes, conjunctivitis, "sand in my eyes" Xerostomia = dry mouth and dysphagia Arthritis Parotid enlargement: increases the risk of B-cell lymphoma (would see unilateral enlargement for this) Autoantibodies to ribonucleoprotein |
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What is the autoimmune reaction to for Sjogrens?
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Ribonucleoprotein
associated with RA Sicca syndrome: dry eyes, dry mouth, nasal and vaginal dryness, chronic bronchitis, reflux esophagitis w/out arthritis |
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What can cause hyperuricemia?
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Lesch-Nyhan syndrome
deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). On X-chromosome so affects males von Gierke's this is a glycogen storage disease |
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How do acute treatments for gout differ from chronic ones?
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acute: NSAIDs, colchicine
Chronic: Allopurinol (xanthine oxidase inhibitor) Probenecid (uricosurics which decreases reabsorption of uric acid, thus increasing excretion) |
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How does crystal formation in gout differ from pseudogout?
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gout = monosodium urate crystals what are needle shaped and negatively birefringment. Yellow is parallel, blue is perpendicular
pseudogout: calcium pyrophosphate crystals that are rhomboid shaped. weakly positive birefringent. Affects the large joints. yellow is perpendicular, blue is parallel Treat: NSAIDs, steroids, colchicine |
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Can I name the symptoms of SLE?
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Of course I am, I'M DAMN SHARP!!!
Immunoglobulin (anti dsDNA, phospholipid) Malar rash Discoid rash Antinuclear antibody Mucositis (oropharyngeal ulcers) Neurologic disorders Serositis (pleuritis, pericarditis) Hematologic disorders Arthritis Renal disorders Photosensitivity |
