Updated: 11/26/2019


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  • A 60-year-old man presents to the emergency department for severe left knee pain. His symptom began approximately 8 hours prior to presentation. He denies trauma to the joint and this is the first time this occurred. Medical history is significant for hemochromatosis managed with weekly phlebotomy. On physical exam, the left knee is erythematous, warm, enlarged, and tender to palpation. Radiography of the affected joint demonstrates chondrocalcinosis. Joint aspiration demonstrates a leukocyte count of 2500/mm3 with a negative Gram stain. Polarized microscopy shows weakly positively birefringent rhomboid crystals.
  • Clinical definition
    • a metabolic arthropathy due to deposition of calcium pyrophosphate dihydrate (CPP) in connective tissue
  • Epidemiology
    • risk factors
      • radiographic CPP deposition increases with age
  • Etiology
    • CPP deposition in joints
  • Pathogenesis 
    • aging and/or genetic factors may result in increased adenosine triphosphate breakdown producing inorganic pyrophosphate 
      • CPP is produced after inorganic pyrophosphate binds with calcium
        • CPP then deposits in cartilage and synovial fluid leading to a synovitis
  • Associated conditions
    • hemochromatosis  
    • hyperparathyroidism
    • hypomagnesemia
      • can be seen in Gitelman and Bartter syndrome
    • joint trauma, surgery, and severe medical illness
      • these conditions can provoke an acute attack
  • Prognosis
    • acute attacks typically resolve in 10 days
    • patients may experience functional limitation due to joint damage
    • may resemble osteoarthritis or rheumatoid arthritis
  • Symptoms
    • asymptomatic (most cases)
    • acute attack (pseudogout)
      • typically affects the wrists, knees, and metacarpophalangeal joints
      • clinically indistinguishable from gout
      • symptoms and physical exam findings include
        • pain
        • erythema
        • warmth
        • swelling
        • disability of the affected joint
    • "pseudo-rheumatoid arthritis"
      • inflammatory arthritis symptoms
        • joint pain and morning stiffness
    • pyrophosphate arthropathy
      • resembles osteoarthritis 
  • Radiography
    • indication
      • to assess the affected joint
    • findings
      • chondrocalcinosis and degenerative changes 
        • chondrocalcinosis appears as hyperdensities that are punctate and linear  
  • Arthrocentesis
    • confirms the diagnosis
    • Gram stain and culture should always be performed since infection could co-exist
    • leukocyte count is 2,000-100,000/mm3
      • > 50% polymorphonuclear cells 
    • polarized microscopy demonstrates weakly positively birefringent rhomboid crystals  
      • blue when parallel to light and yellow when perpendicular to light
  • Gout 
    • differentiating factor
      • polarized microscopy demonstrates negatively birefringent crystals 
      • more commonly affects the first metatarsophalangeal (MTP) joint 
  • Conservative
    • observation
      • indication
        • in patients with asymptomatic chondrocalcinosis
  • Medical
    • nonsteroidal anti-inflammatory drugs (NSAIDs)
      • indication
        • an initial treatment option for pseudogout
    • colchicine
      • indication
        • an initial treatment option for pseudogout
    • glucocorticoids
      • indications
        • injections of the affected joint is typically used in patients with < 2 involved joints
        • oral medications are typically used in patients with > 2 involved joints
  • Joint damage


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Questions (3)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2

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(M2.RH.73) A 64-year-old male presents to his primary care physician with a chief complaint of left knee pain. He describes acute-onset knee pain last evening that was accompanied by redness of the skin around the joint. He denies any precipitating injury or recent activity that could have caused this pain. He describes a similar episode that occurred in his right knee 2 months ago; he did not seek medical treatment, and the pain mitigated after 5 days. Physical examination is significant for the following: left knee is warm-to-touch, erythematous, and extremely tender to palpation; range of motion in flexion and extension is limited by pain; crepitus noted with passive movement of the knee joint. The patient is noted to be afebrile with all vital signs within normal limits. Aspiration of the left knee joint is ordered and reveals the findings shown in Figure A. Which of the following findings could also be seen in this patient, associated with their current diagnosis? Review Topic | Tested Concept

QID: 106581

Decreased serum calcium levels and elevated phosphate levels




Autoimmune destruction of pancreatic islet cells and elevated blood glucose levels




Insulin insensitivity and elevated blood glucose levels




Bronzing of the skin and elevated blood glucose levels




Kayser-Fleischer rings and decreased serum ceruloplasmin



M2 A

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