1.5 - Hypophosphatemia & Hyperphosphatemia

Question 1

What is hypophosphatemia?

Answer 1

• Serum phosphorous less than 2.5 mg/dl. (Normal is 2.5 – 4.5 mg/dl).
• If the value is less than 1.5 mg/dl, it is considered a severe deficit.
• Up to 5% of hospitalized patients will exhibit this abnormality. The prevalence increases to 30-50% in alcoholic patients and patients with severe sepsis or trauma.

Question 2

What role does phosphorous play in the body?

Answer 2

Phosphorous is critical for bone formation and cellular energy metabolism

Question 3

What are the 6 main causes of hypophosphatemia?

Answer 3

1. Urinary phosphorous losses - The kidneys play an important role in phosphate balance. Renal phosphate transport occurs in the proximal and distal tubules.

• Diuretics
• DKA- osmotic diuresis
• Hyperparathyroidism
• Renal tubular defects including Fanconi’s Syndrome and Amphotericin B toxicity

2. Cellular uptake, transcellular shift

• Increased glucose utilization seen in the treatment of DKA with use of insulin, alcohol withdrawal or TPN administration.
• Acute respiratory alkalosis-Extreme hyperventilation (PCO2 <20 mmHg) can lower phosphorous levels acutely
• Burn patients- multifactorial, due to decreased absorption and poor oral intake

3. Deficient GI intake or absorption - seen in chronic ETOH use and use of oral phosphate binders. There is little regulation of gut absorption of phosphorous. Vitamin D does have a mild stimulatory effect. Approximately 80% of dietary phosphate is absorbed in the small intestine.

4. Malabsorption syndromes - These patients have a decreased phosphorous level due to decreased intake. During carbohydrate refeeding in these patients the endogenous release of insulin shifts phosphorous intracellularly.

5. Hemolysis - due to severe hypophosphatemia; CBC, increased serum free hemoglobin and decreased haptoglobin. Defective clots retraction and thrombocytopenia can occur which can aggravate mucosal hemorrhage

6. Rhabdomyolysis - due to severe hypophosphatemia, especially in alcoholics. Increased creatinine kinase (CK) level and positive urinary myoglobin

Question 4

Describe the role between hyperparathyroidism and hypophosphatemia

Answer 4

With hyperparathyroidism there is increased renal excretion with high levels of PTH. Hungry bone syndrome can occur after parathyroidectomy. There is a marked deposition of calcium and phosphate in the bone in the immediate post-operative period leading to low levels of phosphorus

Question 5

What are the subjective/physical exam findings associated with hypophosphatemia?

Answer 5

• Subjective: Severe hypophosphatemia can lead to a metabolic encephalopathy that results from ATP depletion. Patients may complain of irritability, confusion, weakness and paresthesia. The variety of symptoms depend on the severity and chronicity of the phosphate depletion
• Objective (physical findings): Muscle weakness, proximal myopathy, dysphagia and ileus (all effects on the smooth muscle). Pulmonary function can also be impacted with impaired diaphragmatic contractility. In critically ill patients this can lead to prolonged mechanical ventilation

Question 6

What diagnostic/laboratory tests are used to diagnose hypophosphatemia?

Answer 6

• Serum phosphorous is less than 2.5 mg/dl
• Look for a metabolic acidosis with a decreased serum bicarbonate and arterial pH
• EKG – there is an increased incidence of ventricular arrhythmias in the setting of an acute MI. If these patients require emergent heart surgery, there is generally an increased need for vasoactive drug support
• If the cause is not apparent from the clinical situation, a measurement of urine phosphorous excretion helps define the mechanism.
  
  • Renal excretion of > 100 mg by 24 hour urine collection indicates excessive renal losses
  • Low serum 25(OH)D3 suggests dietary Vitamin D deficiency
• iii. An elevated intact PTH may be seen in primary or secondary hyperparathyroidism

Question 7

How do you treat a patient with hypophosphatemia?

Answer 7

• If present, Vitamin D deficiency should be treated first
• Oral replacements with sodium or potassium neutral phosphorous (Neutra phos, K-Phos Neutral). 1-2 grams PO daily in divided doses
• IV options include a solution of sodium or potassium phosphate 2 mg phosphorous/kg in ½ NS over 6 hours. For a higher dose, give 5 mg/kg over 12 hours.

Question 8

What is hyperphosphatemia?

Answer 8

• It is an increased serum phosphorous greater than 5 mg/dl (normal 2.5-4.5 mg/dl)
• Hyperphosphatemia is a stimulus for hyperparathyroidism

Question 9

What are 3 common causes for hyperphosphatemia?

Answer 9

1. Decreased renal excretion - acute or chronic renal failure

• GFR is usually less than 25 ml/min
• This is the most common cause of persistent hyperphosphatemia
• Hyperphosphatemia has been associated with increased mortality and morbidity

2. Redistribution of phosphorous from cell to extracellular fluids

• Tumor lysis syndrome: post chemotherapy for leukemia or lymphoma
• Rhabdomyolysis or crush injury
• Acute respiratory acidosis, metabolic acidosis and hypoinsulinemia reduce phosphorous flux into the cells and contribute to the hyperphosphatemia sometimes seen in DKA

3. Increased intestinal absorption/increased intake – most commonly seen in the setting of impaired renal function

• Use of phosphate containing salts or cathartics
• Vitamin D therapy especially in renal failure/insufficiency
• Occasionally hypoparathyroidism and pseudohypoparathyroidism reduce renal phosphorous clearance as well

Question 10

What are the subjective and objective findings on physical exam of hyperphosphatemia?

Answer 10

Subjective: None or symptoms related to hypocalcemia

Objective (physical findings):

• Ectopic tissue calcification (serum phosphorous [P] x serum Ca) greater than 55
  
  • Sites: cornea or acute conjunctivitis, grainy feeling of skin itching, vascular calcification seen on X-ray or CT. Other sites can include cardiac tissue with valvular and arterial calcification, conduction defects on EKG. These can increase cardiac mortality. Calciphylaxis is the tissue ischemic that can result from the calcification of smaller blood vessels with thrombosis.
• Chronic hyperphosphatemia contributes to the development of renal osteodystrophy

Question 11

What laboratory/diagnostic tests are used to diagnose hyperphosphatemia?

Answer 11

1. Serum phosphorous levels greater than 5 mg/dl in adults (> 6 in children)

An elevated serum phosphorous can be accompanied by a low calcium as a result of intravascular chelation of calcium by phosphorous

2. Check BUN, serum creatinine or creatinine clearance for renal insufficiency.

• In patients with GFR 30-59 mL/min, measure the serum phosphate and calcium every 6 months; increase frequency as GFR decreases

3. PTH and vitamin D levels.

• PTH increases phosphate excretion. Vitamin D deficiency or resistance can cause hypophosphatemia both by decreasing GI phosphate absorption and by causing hypocalcemia and secondary hyperparathyroidism that results in more urinary phosphate excretion.

4. Check ABG

• If the patient is hypoventilating,

Question 12

How do you treat patients with hyperphosphatemia?

Answer 12

• Peritoneal or hemodialysis for patients with renal failure or acute hyperphosphatemia.
  
  • Recovery of renal function will correct the condition within 12 hours. Saline and/or acetazolamide (15 mg/kg every 48 hours) can be given to induce phosphaturia if needed for more aggressive treatment
• Dietary restriction on phosphorous (800-1000 mg/daily)
• Patients with chronic hyperphosphatemia will benefit from oral phosphate binders:
  
  • Calcium acetate 667-1334 mg PO TID with meals
  • Sevelamer 800-3200 mg PO TID with meals
  • iLanthanum 500-1000 mg PO TID with meals