• 5 Classic Causes of Hypoxemia
  • V-Q Mismatch (elevated A-a gradient)
  • Diffusion problems (elevated A-a gradient)
  • Shunting (right to left shunt, PE) (Elevated A-a gradient)
  • Hypoventilation (normal A-a gradient)
  • Altitude, low inspired FiO2 (normal A-a gradient)
• Illness script for PCP Pneumonia: Usually HIV +, chronic non-productive cough (due to high viscosity of sputum), often normal lung exam and chest film, may see ground glass opacities in the bilateral lower lung fields, hypoxia worse with exertion
• Start steroids in addition to Bactrim for FiO2 < 70 or A-a gradient > 35, treatment of PCP fungal death causes a profound inflammatory reaction which is why steroids decrease mortality, treatment course is for 21 days
• Prophylaxis for PCP in HIV for CD4 < 200, 95% effective in preventing PCP

Teaching Pearls:

• Periodic Paralysis occurs as a result of genetic channelopathies that can cause bilateral UE and LE weakness
  • More pronounced in proximal vs distal muscle groups
  • No loss of bulbar muscle functions or respiratory muscles
  • Hypo or a-reflexic on exam
  • Evidence of hypokalemia on labs.
  • Seen in younger patients <20 years of age.
  • Symptoms occur during rest after strenuous exercise, high carbohydrate diet, fasting state
• Primary acquired cause of periodic paralysis is due to thyrotoxicosis
  • Theorized to increased Na/K channels causing hyperpolarization, making it harder to reach threshold to set off action potential.
  • Classically seen in Asian young males
  • Seen in younger patients >20 years of age.
• Differential Diagnosis
  • Myasthenia Gravis
    • Bulbar muscle involvement that gets worse with activity
  • GBS
    • Ascending motor and sensory involvement, symmetric
  • Tick Paralysis
    • Motor abnormalities, no sensory defect, asymmetric
  • Botulism
    • Bulbar involvement, spread in craniocaudal direction
  • Acute myelopathy
    • Motor involvement, hyperreflexic
• Treatment
  • Treat underlying etiology of periodic paralysis
  • Behavioral modification
    • Avoid strenuous exercise and high carbohydrate meal intake
  • Oral medications
    • Consider acetazolamide
    • Consider spironolactone

A special thank you to Dr. Lee Levitt for coming to morning report to participate in this interesting case!

Teaching Pearls:

• Discrepancy of a low O2sat along with normal PaO2 is classically seen with methemoglobinemia.
  • Other causes include poor perfusion state such as vasoconstriction, hypothermia, or any other conditions that cause poor flow state.
  • Methemoglobin – Iron within hemoglobin exists as the oxidized state (+3), causing decreased affinity for oxygen binding.
• Carboxyhemoglobin – when carbon monoxide binds to hemoglobin.
  • Hemoglobin has a very high affinity for CO compared to O2. Causes the oxygen dissociation curve to shift to the left, leading to decreased ability for O2 unloading.
  • Pulse oximetry cannot distinguish between carboxyhemoglobin and oxyhemoglobin.
• Workup of anemia
  • Underproduction
  • Blood loss
  • Increased destruction (hemolysis)
• Reticulocyte count – important to correct for degree of anemia and time of maturation.
  • High corrected reticulocyte index suggestive of blood loss or hemolysis.
  • Low corrected reticulocyte index suggestive of underproduction.
• Hemolysis Labs
  • High LDH, low haptoglobin, indirect hyperbilirubinemia, Coombs test
• Blood Smear
  • Schistocytes, helmet cells suggestive if microangiopathic hemolytic anemia.
  • Bite cells and Heinz bodies suggestive of G6PD deficiency.
  • Spherocytosis suggestive of either hereditary spherocytosis or autoimmune hemolytic anemia.
  • Sickle cells suggestive of sickle cell anemia
  • Target cells suggestive of liver disease (in particular obstructive liver disease), hemoglobinopathy, etc
• Causes of Intrinsic hemolysis
  • RBC membrane defects
    • Example includes hereditary spherocytosis
  • Hemoglobinopathy
    • Examples include thalassemia, sickle cell disease, etc
  • Oxidation Problem
    • Most common example is G6PD deficiency.
• G6PD Deficiency
  • Different variants of disease spectrum
  • X-linked disease – manifest in males
  • Hemolysis precipitated by acute insult, including infections or medications.
  • Medications associated with hemolysis include primaquine, dapsone, sulfa medications, etc.
  • Mediterranean variant associated with favism.
  • Negative G6PD test does not rule out G6PD deficiency in the setting of hemolysis.

Great Discussion today! Thanks to Mike Cruz for presenting.

• Remember that isopropyl alcohol and ethanol causes an osmolar gap without an anion gap.
• Beware of a normal osmolar gap in a patient with a positive volatile screen – this could reflect complete conversion of the parent compound to toxic metabolites

• MKSAP Question: Illness script for Asian female with metastatic lung adenocarcinoma – check for the EGFR mutation
• Approach to Hypocalcemia: Check the PTH level. Causes of hypocalcemia with high PTH include Vit D resistance, pancreatitis, CKD. Causes of hypocalcemia with low PTH include destruction of the parathyroid gland (autoimmune, surgery).
• Clinical Manifestations of Hypocalcemia: Peri-oral numbness, paresthesias, tetany, seizures, papilledema, etc
  • Tetany = neuromuscular irritability
  • Chvostek’s Sign
  • Trousseau’s Sign
• Indications for IV Calcium drip
  • Rapid drop of total calcium to < 7.5
  • Symptomatic hypocalcemia (tetany, carpopedal spasm, seizures)
  • Prolonged QTC
• The two main causes for hypocalcemia in ESRD are hyperphosphatemia (inability to excrete phosphorous) and lack of calcitriol production by the kidney.
• Treatments for secondary hyperparathryoidism in ESRD include phosphorous binders, calcitriol, and calcimimetics.

Teaching Pearls:

• Primary hyperparathyroidism and malignancy comprise of >90% of cases of hypercalcemia.
• Primary hyperparathyroidism is the most common cause of hypercalcemia in outpatient settings.
  • Patients are often asymptomatic and/or have a history of kidney stones
• Malignancy is the most common cause of hypercalcemia in inpatient admissions.
  • Labs often display severe hypercalcemia
  • Patients with severe hypercalcemia are often volume depleted as hypercalcemia can lead to nephrogenic diabetes insipidus
• Initial Workup – First measure the PTH level
  • High PTH: diagnosis is likely primary hyperparathyroidism
  • High normal to mild elevation: think of primary hyperparathyroidism or Familial hypocalciuric hypercalcemia (FHH)
  • Low PTH: proceed onto further tests
• Other work-up labs include PTHrP and vitamin D metabolites. Other considerations include SPEP/UPEP, TSH, Vitamin A, etc.
• FHH differs from primary hyperparathyroidism in that the fractional excretion of Ca in FHH is low, whereas primary hyperparathyroidism is high.
  • Decreased fractional excretion of Calcium leads to lack of nephrolithiasis development.
• Primary hyperparathyroidism has three different pathologic conditions:
  • Adenoma – 89-90%
  • Hyperplasia – 6.8%
  • Carcinoma – 1.2%
• Should consider parathyroid carcinoma in patients with primary hyperparathyroidism and the following:
  • Severe elevations in calcium
  • Severe elevations in PTH
• Management
  • IV fluids NS at 200-300cc/hour to maintain UO at 100-150cc/hour.
    • Loop diuretics only used in the setting of fluid overload
  • Calcitonin – onset of action: hours
    • Concern for tachyphylaxis
  • Bisphosphonates (pamidronate or zolendronate)
    • Onset of action >2 days

Teaching Pearls:

• Presents in 20-60 year old individuals. Diagnosis tends to occur 10 years earlier in blacks than Caucasians.
• Over 90% present with pulmonary findings on imaging.
• About 50% of patients with sarcoidosis are asymptomatic.
• About 30% of patients with sarcoidosis have extrapulmonary manifestations
• Extrapulmonary manifestations include:
  • Cutaneous – can be found on tattooed skin
  • Cardiac – monitor for conduction delays, infiltrative heart diseases
  • Lymph nodes, liver, spleen
  • GI
  • Renal
  • Systemic symptoms
• Differential Diagnosis
  • Infectious
    • HIV, TB, fungal lung diseases
  • Occupational/environmental toxin exposure
  • Hypersensitivity pneumonitis
  • Pneumoconiosis (Beryllium)
  • Langerhans Cell histiocytosis
  • Malignancy (lymphoma)
• Diagnosis is made with the following:
  • Clinical and radiographic findings
  • Excluding other potential causes
  • Tissue biopsy
• Lofgren’s syndrome
  • Erythema nodosum, bilateral hilar adenopathy, fever, arthritis
  • Biopsy not needed if Lofgren’s syndrome is present (high specificity)
  • Prognosis – fantastic; treatment – NSAIDs
  • A Boards favorite topic. (Very high yield)

Congratulations to our 8 poster presenters for representing the VMC family at SGIM Northern California-Hawaii Conference!

Our very own David Wang scored FIRST PLACE on his poster presentation!!! Congratulations again!!

Teaching Pearls:

• Inherited Thrombotic Diseases
  • Factor V Leiden
    • Moderate risk of thrombosis
  • Prothrombin G2120A mutation
    • Moderate risk of thrombosis
  • Protein C Deficiency (higher risk of thrombosis)
  • Protein S deficiency (higher risk of thrombosis)
  • ATIII Deficiency (higher risk of thrombosis)
• Factor V Leiden is the most common inherited thrombotic disease
  • Occurs in 5% of Caucasians
  • Heterozygotes have 5-fold increase in thrombosis; double hit has 50-fold increase.
• Treatments for coagulation reversal
  • FFP
    • Plasma containing normal factors
    • May take 1-2 hours for action
    • Higher volume load
  • Kcentra
    • Concentrate with factors II, VII, IX, and X
    • Immediate
  • Vitamin K
    • Duration of action approximately 4-12 hours

SJS/TEN Teaching Pearls:

• SJS/TEN are severe mucocutaneous lesions
  • <10% of epidermal involvement categorized as SJS.
  • >30% of epidermal involvement categorized as TEN
  • 10-30% of epidermal involvement categorized as SJS/TEN
• Most commonly caused by:
  • Medications (allopurinol, anticonvulsants, sulfonamides, NSAIDS)
  • Infectious (mycoplasma pneumonia, CMV)
• Clinical Manifestations:
  • Prodrome of fever and flu-like symptoms 1-3 days
  • Development of mucocutaneous and skin lesions that start as erythematous macules.
  • Progress to vesicles and bullae formation within days prior to sloughing.
  • Mucocutaneous involvement occurs in >90% of patients (oral, ocular, urogenital).
• Complications
  • Fluid balance and electrolyte abnormalities
  • Infections
    • Staph Aureus and Pseudomonas
    • Fungemia
    • No role for empiric antibiotics.
  • Pulmonary
    • ARDS
    • Pneumonia
• Management
  • High level of suspicion as early withdrawal of medications important for treatment.
  • Symptomatic care
    • Consult ophtho, burn, and derm
    • Patient should be transferred to ICU burn care if moderate to high severity of disease.