Electrolyte Disorders: Calcium, Phosphorus, Magnesium

Electrolyte Disorders: Calcium, Phosphorus, and Magnesium

• Learning Objectives:
  • Describe the physiological roles of calcium, phosphorus, and magnesium in the human body.
  • Identify common causes of calcium, phosphorus, and magnesium disorders.
  • Recognize calcium, phosphorus, and magnesium disorders based on clinical presentation.
  • Explain the mechanisms of action of therapies for hypercalcemia and hyperphosphatemia.
  • Design a patient care plan and treatment regimen for calcium, phosphorus, and magnesium disorders.

Electrolyte Abnormalities: Treatment Indications and Goals

• Indications: Dependent upon:

  • Severity (how far the electrolyte level is from normal)
  • Acuity of development (how quickly the disorder developed)
  • Acute (<48 hours); Chronic (>48 hours)

• Goals:

  • Reverse signs and symptoms
  • Identify and correct the underlying cause
  • Restore electrolytes to normal values

Calcium

• Disorders of calcium homeostasis: Related to calcium content in the extracellular fluid (ECF)
• Physiologically active calcium: Free calcium (ionized calcium) is the physiologically active form.
• Bound calcium: A significant portion of calcium is bound to plasma protein, primarily albumin
• Corrected Calcium: Calculated when albumin is low. Formula: Measured calcium + (0.8 x (4 - Measured albumin))
• Regulation: Ionized calcium levels are tightly regulated by parathyroid hormone (PTH), phosphorus, vitamin D, and calcitonin.

Hypercalcemia

• Definition: Serum calcium > 10.5 mg/dL (2.63 mmol/L) or ionized calcium > 5.6 mg/dL
• Severity: Categorized based on total and ionized calcium levels:
  • Mild: 10.5-11.9 mg/dL (5.6-8 mg/dL ionized)
  • Moderate: 12-13.9 mg/dL (8-10 mg/dL ionized)
  • Severe: 14-16 mg/dL (10-12 mg/dL ionized)

Hypercalcemia: Treatment Algorithm

• Symptomatic (Ca>12 mg/dL):

  • eGFR >30: IV saline, loop diuretics, calcitonin
  • eGFR <30 or HF with EF<25%: Calcitonin, other interventions based on suspected cause
  • ESRD: Hemodialysis

• Asymptomatic (Ca<12 mg/dL):

  • Observe, check for underlying causes, adjust medications as needed

IV Saline Rehydration

• Mechanism: Volume expansion with normal saline to increase natriuresis and urinary calcium excretion.
• Treatment: Bolus (1-2 liters) followed by maintenance infusion (250-300 mL/hr) until fluid resuscitation and serum calcium are close to the upper limit of normal.
• Duration: Until fluid resuscitation is complete and serum calcium is close to normal, usually within 24-48 hours.

Loop Diuretics

• Mechanism: Block calcium/sodium reabsorption in the loop of Henle.
• Use: Should always be used in conjunction with IV isotonic fluids. Never used as monotherapy.
• Place in therapy: In patients with normal to moderately impaired kidney function when serum calcium is >12 mg/dL, or patient is symptomatic.

Calcitonin

• Mechanism: Inhibits osteoclast activity and reduces renal tubular calcium reabsorption promoting calciuresis.
• Place in therapy:
  • First-line for patients with a contraindication to IV saline rehydration (e.g., heart failure with EF<25% or eGFR<30)

Bisphosphonates (IV)

• Mechanism of action: Block bone resorption and inhibit osteoclasts.
• Place in therapy: First-line for long-term, chronic treatment for moderate-severe hypercalcemia of malignancy if other treatments fail. Often used for outpatient management.
• Pharmacokinetics: Slow onset (calcium declines in 2 days; reaches nadir in 7 days)
• Adverse Effects:
  • Fever
  • Bone pain
  • Osteonecrosis of the jaw (rare)
  • Acute tubular necrosis (rare)

Denosumab

• Mechanism of action: Monoclonal antibody that inhibits RANKL.
• Place in therapy: Chronic treatment of hypercalcemia of malignancy in patients who have failed IV bisphosphonate therapy or cannot continue therapy due to severe renal dysfunction.

Corticosteroids

• Mechanism of Action: Reduce gastrointestinal calcium absorption by inhibiting vitamin D activation
• Place in Therapy: Used for hypercalcemia associated with malignancies (multiple myeloma, leukemia, and lymphoma) that overproduce calcitriol.
• Treatment: Prednisone (40-60 mg PO) or equivalent, for 3-5 days followed by maintenance dose (10-30 mg/day).
• Pharmacokinetics: Initial response takes 3-5 days followed by an increase in urinary calcium excretion within 7-10 days
• Adverse effects: Diabetes mellitus, osteoporosis, increased susceptibility to infection

Hypocalcemia

• Definition: Serum calcium < 8.5 mg/dL (2.3 mmol/L) or ionized calcium < 4.4 mg/dL (1.1 mmol/L) when serum albumin is >4 g/dL.

Hypocalcemia: Treatment Algorithm

• Symptomatic, Acute: IV calcium (chloride or gluconate) bolus over 10 minutes.
• Asymptomatic, Acute: IV calcium gluconate bolus at 1 gram/hour.
• Asymptomatic, Chronic: Oral calcium supplementation (1-3 grams/day)

Hypocalcemia: Chronic Asymptomatic Treatment

• Oral Calcium Supplementation: 1-3 grams of elemental calcium per day, divided doses.
• Vitamin D Supplementation: 800-1000 IU daily of Vitamin D3 (cholecalciferol); or 50,000 IU once weekly of Vitamin D2 (ergocalciferol)

Common Calcium Salts

• Calcium carbonate (40%): High elemental calcium content
• Calcium citrate (21%): Lower absorption rate
• Calcium lactate (13%): Less bioavailability
• Calcium gluconate (9%): Least amount of elemental calcium

Phosphorus

• Role: Major intracellular anion; plays crucial roles in energy metabolism, bone mineralization, and cellular function.
• Normal range: 2.5-4.5 mg/dL (0.9-1.45 mmol/L)
• Regulation: Controlled by GI tract, bone, and kidney

Hyperphosphatemia

• Definition: Serum phosphate > 4.5 mg/dL (1.45 mmol/L)

Hyperphosphatemia: Treatment

• Asymptomatic or mild GI symptoms: Reduce dietary phosphorus intake and use phosphate binding therapy.
• Severe: IV calcium administration (calcium chloride or gluconate over 10 minutes) to reduce exogenous intake of phosphate. Hemodialysis if symptoms persist.

Phosphate Binders

• Mechanism of Action: Bind dietary phosphorus in the GI tract and excrete in feces.
• Calcium-based binders: Used if concomitant hypocalcemia/normocalcemia and eGFR > 30 (e.g., calcium acetate, calcium carbonate).
• Non-elemental binders: Used if concomitant hypercalcemia/normocalcemia and eGFR< 30 (e.g., sevelamer carbonate, sevelamer HCl).
• Iron-containing binders: Newest, most expensive, best for patients with ESRD on dialysis (e.g., sucroseferrix oxyhydroxide, ferric citrate)
• Aluminum-containing binders: Not appropriate for long-term use due to adverse side effects (e.g., aluminum hydroxide).

Hypophosphatemia

• Definition: Serum phosphorus is <2.5 mg/dL
• Severity: Categorized into mild, moderate, and severe based on specific serum phosphorus levels.

Hypophosphatemia: Treatment

• Mild-moderate (1-2 mg/dL): Oral phosphate salts (1.5-2 grams daily)
• Severe (<1 mg/dL): IV phosphate repletion with sodium or potassium phosphate salts

Magnesium

• Distribution: Primarily in bone (67%) and muscle (20%).
• Normal range: 1.7-2.4 mg/dL (1.4-1.8 mEq/L)
• Homeostasis: Maintained by a balance between intake, absorption in the small bowel, filtration, reabsorption, and excretion in the kidneys.

Hypermagnesemia

• Definition: Serum magnesium >2.4 mg/dL (2 mEq/L).

Hypermagnesemia: Treatment

• Reduce magnesium intake.
• Antagonize magnesium effects: IV calcium.
• Enhance magnesium elimination: Normal renal function (1-3): Furosemide IV bolus; ESRD: dialysis

Hypomagnesemia

• Definition: Serum magnesium < 1.7 mg/dL (1.4 mEq/L).

Hypomagnesemia: Treatment

• Mild-Moderate (1.2-1.7 mg/dL): PO/IV supplementation with magnesium oxide (400-800 mg PO daily) or magnesium sulfate (1-2 g IV).
• Severe (<1.2 mg/dL): IV magnesium sulfate (8-12 g divided doses over 24 hours) or (4-6 g divided doses over 3-5 days).

This quiz covers electrolyte disorders focusing on calcium, phosphorus, and magnesium. Participants will learn about their physiological roles, common disorders, and treatment strategies. You'll also explore mechanisms of action for therapies and patient care plan design.