Electrolyte abnormalities

Calcium: normal range (8 – 10.3 mg/dL)

Ca pathophysiology and causes of hypercalcemia

Hypercalcemia (Serum Ca of >10.3 mg/dL, or ionized Ca > 5.2 )

Causes:

Mnemonic: CHIMPANZEES (Calcium supplementation, Hyperparathyroidism, Hyperthyroidism, Immobility, Iatrogenic, Metastatic, Milk-alkali synd, Paget's disease of bone, Addison's disease, Acromegaly, ZE- syndrome (MEN-1), Excessive Vit A, Excessive Vit D, Sarcoidosis)

Check Sr. albumin level. Measure intact PTH. Elevated in primary hyperparathyroidism and invariably suppressed in patients with hypercalcemia due to malignancy.

Others: Antacid abuse, Lithium; TB; Malignancies: Colon, lung, breast, prostate, multiple myeloma.

Humoral hypercalcemia of malignancy: tumor produces PTH-rp (PTH related peptide). Stimulates bone resorption and renal calcium reabsorption. PTH-rp is not detectable by usual PTH immunoassay. Specific immunoassay exists for PTH-rp.

Local osteolytic hypercalcemia: malignant cells in multiple myeloma or solid tumors with bone metastases may cause osteoclast stimulation. Osteoclast activating factors (OAFs) are interleukins, TGF, and other cytokines.

Tx:

Acute management: presence of severe sx (polyuria, dehydration, mental status changes), Sr. Ca >12 mg/dL

• Correct hypovolemia: 1^st replace ECF volume: NS IV @ 250 - 500 mL/hr. Give ~ 3 – 6 L in 1^st 24 hr, or until the ECF volume deficit is partially corrected. Get at least 2 L +ve fluid balance in the first 24 hours or to sustain a UO of 100 - 150 mL/h. Watch for signs of volume overload in CHF Pts. Natriuresis → ▲ renal Ca excretion.

• 2^nd. Saline diuresis: NS @ 100 – 200 ml/hr.

  • Lasix 20 – 80 mg IV q6 – 12 hr given only if there is clinical evidence of CHF and aggressive IVF cannot be given for fear of volume overload and tipping the patient into CHF. No THZ diuretics. Start this only after ECF volume is restored. Promotes natriuresis and hence ▲ Ca excretion.

• Replace Mg, K, and Phos.

• Monitor UO. Monitor for HF. Check electrolytes q6 – 12h.

• Severe hypercalcemia (>13.5 mg/dL): Biphosphonates. Aredia (pamidronate): 60 - 90 mg in NS 500 ml - 1 L or D5W over 2 – 4 hours. Single dose only; Or,

• Zoledronate is newer and more potent, 4 mg in 100 ml 0.9% saline or D5W infused over 15 minutes. Do not retreat for 7 days. Didronel (etidronate): 7.5 mg/kg IV qd x 3d. Check for renal dosing.

• Hydration is important during treatment with biphosphonates.

• Renal insufficiency is a relative contraindication to their use. Risk of jaw osteonecrosis. Inhibition of osteoclasts occur.

• Takes 1-2 days to act

• Salmon calcitonin , 4 – 8 IU/kg, SC or IM q6 – 12h, lowers serum calcium by 1 - 2 mg/dL within few hours. It is safe in renal failure. Tachyphylaxis occurs after several days. Has an analgesic quality in patients with skeletal metastases. Can be used with biphosphonates for longer effect.

• Prednisone, 20 – 60 mg PO bid, in CA 2° multiple myeloma, sarcoidosis, hematologic malignancies, and Vit D intoxication. Taper after Ca starts ¯. Inhibits cytokine release, by direct cytolytic effects on tumor cells, inhibits intestinal Ca++ absorption, and increases urinary Ca++ excretion. Takes 5 - 10 days for serum Ca++ to fall.

• Oral phosphate should be used only if Sr. phosphorus level < 3 mg/dL and renal function is normal. 0.5 - 1 g elemental phosphorus PO tid. Reduce dose if Sr. Phos level <4.5 mg/dL of if Sr. Ca++ x Sr. PO4 (measured in mg/dL) >60. IV phosphate should never be used to treat hypercalcemia.

• Gallium nitrate inhibits bone resorption, equal efficacy to biphosphonates IV, with similar delayed onset of 2 days. Given as 100 - 200 mg/m2/d continuous infusion for up to 5 days, unless normocalcemia is achieved sooner. Risk of nephrotoxicity; c/i if Sr. Cr >2.5 mg/dL.

• Pts with ESRD on HD will require dialysate with low Ca.

Chronic management:

• Primary hyperparathyroidism: Many patients have a benign course, asx, and with minor fluctuations in serum calcium conc. Parathyroidectomy (high success rate) indicated when:

  • Corrected serum calcium > 1 mg/dL over the upper limit of normal

  • Calciuria >400 mg/d

  • Renal insufficiency

  • Reduced bone mass (T score of <2.5 or less by DEXA)

  • Age <50 years

  • Unfeasibility of long-term follow up

• Medical Therapy: for pts who are not surgical candidates. Oral hydration with a high salt diet, daily physical activity to reduced bone resorption, and avoidance of thiazide diuretics. Oral biphosphonates, estrogen replacement therapy or raloxifene in postmenopausal women can be considered in the appropriate clinical context. Cinacalcet, an activator of calcium-sensing rcp, is shown to reduce PTH secretion and Sr. Ca levels, although not approved for use in primary hyperparathyroidism at this time.

• Malignant hypercalcemia. Biphosphonate, glucocorticoid, and a calcium restricted diet <400 mg/d can be tried, but rarely succeed for a long time unless the cancer responds to treatment.

Hypocalcemia (< 8.4 mg/dL with a normal serum albumin or an ionized calcium < 4.2 mg/dL)

• Check serum (free) ionized calcium; it is the biologically active form. Check iPTH, vitD-25 (OH)D3, ECG prolonged QT and bradycardia.

• Causes: renal failure, hypoparathyroidism (including neck surgery - usually due to ischemia of the parathyroid glands), severe hypomagnesemia, acute pancreatitis, rhabdomyolysis, tumor lysis syndrome, vitamin D deficiency, pseudohypoparathyroidism (PTH resistance), and, rarely, multiple citrated blood transfusions. Drugs: cisplatin, cytosine arabinoside, pentamidine, ketoconazole, fluoride, cimetidine, ethanol, foscarnet, fluoroquinolones, and phenytoin.

  • Ca pathophysiology and causes of hypocalcemia

• Potentiates digoxin toxicity.

Clinical features:

• Depend on degree and rate of hypocalcemia.

• Acute moderate hypocalcemia > ▲ excitability of nerves and muscles > circumoral paresthesiae, distal paresthesiae, tetany, Chvostek's (tapping facial nerve → contraction of facial muscles), Trousseau's (inflation of BP cuff → capal spasm).

• Acute severe hypocalcemia: laryngospasm, confusion, psychosis, ▲ ICP, sz, or vascular collapse with bradycardia, ▲QT, and decompensated CHF.

• Renal osteodystrophy; ▼VitD & ▼PTH in renal failure, results in osteomalacia and osteitis fibrosa cystica (due to ▲PTH)

History: Neck surgery - postoperative hypoparathyroidism, autoimmune, infiltrative disease, FH of hypocalcemia, drug induced, vitamin D deficiency (uremia), liver dz, nephrotic syn, medication review, critically ill (cytokine mediated ▼ PTH and calcitriol release)

Physical exam: Trousseau's sign - carpopedal spasm with BP inflated ▲ SBP for 3 min. Chvostek's sign - twitching of facial muscles when facial nerve is tapped anterior to the ear. These signs are know as signs of latent tetany.

Tx:

Acute management is aggressive:

• Check medications, hyperphosphatemia with hypocalcemia with symptoms > HD - ? - Adm. of Ca > ▲ in Ca x Phos product leading to ectopic calcification.

• Hyperphosphatemia without sx: treat hyperphosphatemia first. ▼ phosophorus before Ca++ supplementation.

• Hypomagnesemia: Tx first to correct hypocalcemia. Give MgSO4, 2 g IVPB x 15 min > F/up IV infusion if renal failure is absent.

• Sr Ca: 6.7, Ca Gluconate 1-2 gm IVPB x (1, 2, 3, spaced 2 hr apart) given in 20 minutes. Calcium gluconate (reduced risk of tissue toxicity with extravasation) in severe symptomatic hypocalcemia. 1 ampule of calcium gluoconate, is 10 mL of 10% sol (100 mg/mL) (i.e) 1000 mg of calcium gluconate and ~ 90 mg of elemental calcium. Add 1 - 2 ampules in 50 - 100 mL of D5W and given in 10 - 20 min. Tx effect is transient, so f/up continuous infusions of 0.15 - 1.5 mg/kg/hr of elemental calcium.

• 100 mL of 10% calcium gluconate contains ~900 mg elemental ca/L = ~ 1 mg of elemental calcium/mL. Infuse starting rate @ 50 mL/hr (~50 mg of elemental Ca/L).

• Oscal (CaCO3), 500 mg 1 – 2 tid

Chronic management:

• Tx w/ Ca++ supplements, vit-D, CaCO3 (40% elemental ca) 1 - 2 gm PO tid, calcium acetate (25% elemental calcium).

• Give apart from meds - why? - minimizes binding w/ phosphorus in diet, thus maximizing GI absorption. Check Sr. Ca levels once or twice weekly to monitor.

• Vitamin D: ergocalciferol, 400 - 1000 IU/d.

  • In renal insufficiency and other d/o impairing vitamin D metabolism. Give ergocalciferol 50,000 IU qwk x 6 - 8 wk, or daily with severe malnutrition or malabsorption.

  • Calcitriol has rapid onset of action: 0.25 mcg daily (0.5 - 0.25 mcg daily) > ▲ enteric absorption of calcium and phosphorus. Check Ca++ and phos. If phos is ▲ - start oral phosphate binders.

Complications: Hypercalcemia. D/c vitamin D or calcium supplements. Check sr. calcium and phos. Restart at lower dose when calcium is normal. Calcitriol induced hypercalcemia resolves in 1 week.

Sodium: normal range (>145 mMol/L):

• 85 - 90% of total body Na+ is extracellular.

• Na+ concentration is the amount of Na+ distributed in a fixed quantity of water.

• Na+ content: total amount of sodium.

• It is customary to provide 75 - 175 mEq of Na⁺ daily.

  • A typical 2 gm Na+ diet provides 86 mEq of Na⁺ day.

Osmotic adaptation of brain cells. The ability of brain cells to adapt by varying the number of intracellular solutes to defend against large water shifts. This can occur in chronic hyponatremia and hypernatremia. This process is initiated by transcellular shifts of K+ and Na+, followed by synthesis, import, or export of organic solutes (so called osmolytes) such as inositol, betaine, and glutamine. During chronic hyponatremia, the brain cells lose solutes, thereby defending cell volume and diminishing neurologic symptoms. The converse occurs during chronic hypernatremia.

Normal plasma osmolality is 275-290 mosmol/kg. The average osmotic threshold for thirst is approximately 295 mosmol/kg and varies among individuals. The osmotic threshold for release of AVP is 280-290 mosmol/kg.

Osmoreceptors are located in anterolateral hypothalamus.

AVP (ADH), a polypeptide synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and secreted by the posterior pituitary gland.

Three steps are required by the kidney to excrete a water load:

1. Filtration and delivery of water and electrolytes to the diluting sites of nephron

2. Active reabsorption of Na+ and Cl- without water in the thick ascending limb of the loop of Henle and, to a lesser extent, in the distal nephron; and

3. Maintenance of dilute urine due to impermeability of the collecting duct to water in the absence of AVP.

Hypernatremia (≥145 mMol/L): hyperosmolality state.

Causes.

• Dx algorithim for eval of hypernatremia.

  • Appropriate renal response to hypernatremia is a small volume of concentrated urine (Uosm >800 mOsm/L).

  • Submaximal urine osmolalilty (Uosm <800 mOsm/L) suggests renal water conservation.

  • Uosm <300 mOsm/L in the setting of hypernatremia suggests complete CDI and NDI.

  • Uosm 300 - 800 mOsm/L can occur from partial forms of DI as well as osmotic diuresis.

    • Differentiate by calculating daily solute excretion (Usom x urine vol in 24 hours).

    • A daily solute excretion of >900 mOsm defines an osmotic diuresis.

  • Response to dDAVP: complete forms of CDI and NDI can be distinguished by administering the vasopressin analog dDAVP, 10 mcg intranasally after careful water restriction. The urine osmolality should increase by at least 50% in complete CDI and does not change in NDI.

• Tx:

  • Rate of correction depends on acuity of its development and the presence of neurological dysfunction.

    • Sx hypernatremia: Do not correct more than 10 - 12 mMol/L/day

    • Chronic Asx hypernatremia: Do not correct more than 5 - 8 mMol/L/day

    • Rate of correction should not exceed 0.5 mmol/L/hr or no more than 12 mmol/L/24 hrs to avoid cerebral edema and precipitate CHF.

    • Give water PO, PEG, or NG tube.

    • 1/2NS IV to replace both H2O and Na+. Each 1L delivers ~500 ml of free H20. Give if Pt has both hypernatremia and hyperglycemia or DM.

    • Traditionally, Calc. body water deficit (L) = (Plasma Na – 140)/140 x TBW (L)

    • Change in Na in mEq/L (mmol/L) from infusing 1 liter of fluid:

      • Change in Na+ = (Na⁺ infusate + K⁺ infusate) - Na⁺ serum DIVIDED (TBW + 1)

      • The formula is a rough guide and does not account for ongoing electrolyte and water losses.

      • As hypernatremia suggests a contraction in water content, TBW is estimated by multiplying lean body wt (kg) by 0.5 in men (rather than 0.6) and 0.4 in women (rather than 0.5)

        • Example: A 70-kg man with diarrhea from laxative abuse presents with obtundation and Sr. Na+ = 164 mEq/L, Sr. K+ = 3. A replacement fluid of D5W with 20 mEq KCl/L is chosen.

          • Change in Na+ with infusing 1 liter of D5W and 20 mEq/L of KCl:

            • (0 + 20) - 164 divided (70 x 0.5) +1

              • = -4 mEq/L

            • Rate of correction: - 12 mEq/L/24 hr

              • - 12/-4 = 3 L.

              • Hourly infusion rate is 3/24 = 0.125 L/hr = 125 ml/hr.

            • Closely monitor electrolytes and pt clinical status.

    • Treat underlying causes:

      • correct hypovolemia with isotonic solution. This takes precedence over correction of hyperosmolar state. Once the Pt is hemodynamically stable, administration of hypotonic fluid can be given to replace the free water deficit.

      • Hypernatremia from iatrogenic causes: stop iatrogenic Na.

      • DI without hypernatremia. DI should not result in hypernatremia if the thirst mechanism is intact. Tx sx polyuria:

        • CDI. dDAVP

        • NDI. Low Na diet, THZ diuretics will decrease polyuria by inducing mild volume depletion. This enhances proximal reabsorption of salt and water, decreasing excess water loss. Decreased protein intake will further reduce urine output by minimizing the solute load that must be excreted.

Hyponatremia(≤135 mMol/L)

Causes

• Excess water relative to sodium in ECFV

• Asymptomatic Pt: no treatment necessary.

• Severe hyponatremia is an acute process, usually h/o <2 days.

• Chronic hyponatremia > 3 days.

• Confusion when Na <125 mmol/L. Stupor, seizures, and coma do not usually occur unless the Na falls acutely <115 mmol/L.

• Clinical assessment of volume status, plasma osmolality, urine osmolality, and urine Na+

• In acute hyponatremia correction:

  • Rate of increase in plasma Na should be 1 - 2 mmol/L/hr for 3 to 4 hours.

  • Rapid correction >12 mmol/L in 24 -hours period can lead to osmotic demyelination syndrome (ODS) or central pontine myelinolysis.

    • Patient will have deteriorating LOC and become comatose.

    • Pre-existing hypokalemia, malnutrition, and alcoholism are other risk factors that can contribute to the development of CPM.

  • After the initial correction, the rate of correction should not exceed 10 - 12 mmol/L in 24 hours period.

  • Fluid administration:

    • 3% NaCl given in ICU settings, for rapid correction.

    • Change in Na in mEq/L (mmol/L) from infusing 1 liter of fluid:

      • Change in Na+ = (Na⁺ infusate + K⁺ infusate) - Na⁺ serum DIVIDED (TBW + 1)

      • The formula is a rough guide and does not account for ongoing electrolyte and water losses.

      • Dividing the desired rate of correction in mEq/L/hr by change in Na+ (mEq/L/L) gives the rate of administration in liters/hr

        • Example: An 80-Kg woman is seizing. Her Sr. Na+ is 108 mEq/L.

          • Rate of correction of Na+ is 1 - 2 mEq/L/hr x 3 - 4 hours, since she is symptomatic. Correction must be acute, but no more than 12 mEq/L in 24 hrs.

          • 3% saline has 513 mEq of Na+ in a liter of the solution.

          • Change in Na⁺ = (513 - 108) divided (80 x 0.5) + 1

          • Change in Na⁺ = 405 divided 41 = 9.8 or approx 10 mEq/L.

          • Therefore, 1 liter of 3% NaCl will increase Sr. Na+ by 10 mEq/L.

          • Rate of correction is 2 mEq/L/hr

            • Rate = 2/10 = 0.2 L or 200 mL/hr

            • Give for 3 - 4 hours, while monitoring Pt. clinical status and Sr. Na+

            • Do not give >1 liter of 3% NaCl, to avoid a change of >10 - 12 mEq/L in 24 hours.

  • If patient is hyperglycemic, calculate corrected Na. Sr. Na⁺ conc. falls by approx. 1.6 mEq/L (mmol/L) for every 100 mg/dL increase in Sr. glucose above 100 mg/dL. Check Sr. glucose.

  • Chronic Ax hyponatremia: Rate of correction, 4 - 8 mEq/L x 24 hour period; or < 0.5 mEq/L/hr.

  • Asx hypovolemic hyonatremia: Give NS to restore intravascular volume. Follow the same calculation as above with 1 L of 0.9% NS.

  • Asx hypervolemic hyponatremia: CHF, cirrhosis often signifies severity of underlying disease. Although effective circulating volume is decreased, the administration of fluid may worsen the volume-overloaded state. Tx the underlying condition, restrict water intake; diuresis may help.

  • Medications:

    • When using medications that promote water loss, lab data and clinical status of pt must be monitored closely, as the water and electrolyte loss cannot be accurately predicted by labs/formulae.

    • Loop diuretics > ▲ urinary excretion of water by reducing the conc. gradient necessary to reabsorb water in the distal nephron and impair the ability to excrete concentrated urine.

    • Lithium and demeclocycline rarely used, except in severe hyponatremia unresponsive to more conservative measures. Interfere with the collecting tubule's ability to respond to ADH.

    • Conivaptan, IV is a vasopressin antagonist that promotes water diuresis and may be useful in the Tx of SIADH.

  • Lifestyle/Risk modification:

    • Oral fluid intake should be less than daily urine output.

    • SIADH should be checked

    • Water restriction

      • if (Urine Na + Urine K)/Sr. Na, <0.5, restrict to 1 L/day

      • if (Urine Na + Urine K)/Sr. Na is 0.5 - 1, restrict to 500 mL/day

      • if (Urine Na + Urine K)/Sr. Na is >1, the Pt has negative renal free water clearance and is actively reabsorbing water.

      • Any amount of water may be retained, consider:

        • High dietary solute load. As the volume of water excreted as urine is governed by a relatively fixed urine osmolality, increasing solute intake with a high-salt, high-protein diet or administration of oral urea (30 - 60 g), may increase the capacity for water excretion and improve the hyponatremia.

    • Correct underlying causes

• SIADH

Magnesium: normal range (1.6 – 3 mg/dL):

• Important role in neuromuscular function.

• ~60% in bone, rest intracellular, 1% in ECF. Sr. Mg, therefore is a poor indicator of intracellular and total body stores and may grossly underestimate total magnesium deficits.

• Mg is the main determinant of Mg conc, and infulences excretion. Hypomag sitmulates tubular resabsorption of mag, whereas hypermag inhibits this.

Hypermagnesemia >2.2 mEq/L

Causes:

• Iatrogenic: drug Tx of hypomagnesemia or eclampsia/preeclampsia

• Renal failure: decreased GFR

• ESRD.

• Magnesium containing antacid abuse in patients with underlying renal insufficiency

• Deficiency in mineralocorticoid secretion

• Massive cell breakdown (tumor lysis, rhabdomyolysis)

• Redistribution: DKA, pheochromocytoma

• Miscellaneous: Lithium toxicity, volume depletion, familial hypocalciuric hypocalcemia. theohphylline intoxication.

Si & Sx: seen only if Sr. Mg >4 mEq/L.

• Hyporeflexia

• Lethargy and weakness that could progress to somonolence and coma.

• Hypotension, bradycardia, and cardiac arrest.

• Acute, severe hypermagnesemia can suppress parathyroid secretion and cause hyporcalcemia

• ECG: bradycardia, prolonged PR, QRS, and QT intervals with Sr. Mg: 5 - 10 mEq/L. Complete heart block or asystole with levels >15 mEq/L.

• Check for renal failure, avoid using Mg preparations in renal Pts.

• Asymptomatic Pt: withdraw Mg products (laxatives and antacids).

• Symptomatic Pt:

  • Supportive therapy, STAT.

  • Mechanical vent if needed for resp failure and temporary pacemaker for significant bradyarrhythmias

  • In severe symptomatic patients with hypermagnesemia with ECG changes:

    • Ca. gluconate 10%, 10 – 20 ml (1 - 2 g) x 10 min, or 10% CaCl2 5 to 10 mg/kg IV to temporize.

    • Pt w/o severe renal dysfunction: Ca. gluconate 10%, 20 ml (2 gm) in a liter of 0.9 NS @ 100 to 200 ml/hr. Furosemide or ethacrynic acid may enhance excretion.

    • In refractory cases Hemodialysis is effective.

Hypomagnesemia (<1.3 mEq/L)

Causes:

• • GI and nutritional: inadequate intake (alcoholics), IV fluid and TPN without magnesium supplementation, chronic diarrhea, prolonged NGT suctioning, small bowel or biliary fistulas, familial magnesium malabsorption, inflammatory bowel disease, laxative abuse, malabsorption (sprue, steatorrhea, chronic pancreatitis).

  • Excessive renal losses: Alcoholism, diabetes, diuretics (thiazide, loop, and osmotic/hyperglycemia), other medications, hormones (hypoparathyroidism, hyperthyroidism, hyperaldosteronism, SIADH, excessive vitamin D, ketoacidosis, renal disease (acute tubular necrosis, interstitial nephritis, glomerulonephritis, post-obstructive diuresis, post-renal transplantation), hypercalcemia/hypophosphatemia, tubular defects (primary magnesium wasting, Welt’s syndrome, Gitelman’s syndrome, renal tubular acidosis)

• resolving ATN (diuretic phase), DKA, hyperaldosteronism, hyperthyroidism, hyperparathyroidism, hypokalemia, hypercalciuria, Bartter's and Gitelman's syndromes.

  • Bartter syndrome is a rare inherited defect in the thick ascending limb of the loop of Henle. It is characterized by hypokalemia, alkalosis, and normal to low blood pressure. There are two types of Bartter syndrome: neonatal and classic. A closely associated disorder, Gitelman syndrome, is milder than both subtypes of Bartter syndrome

• Cellular redistribution: hypoalbuminemia, cirrhosis, insulin/D5W, acute pancreatitis, sweating, burns, prolonged exercise, "hungry bone syndrome" (rapid transfer of calcium into bones following removal of a hyperactive thyroid nodule).

• Drugs: aminoglycosides, amphotericin-B, cisplatin, pentamidine, and cyclosporine.

Si & Sx:

• Neuromuscular: most common early findings. Weakness, hyperreflexia, fasciculations, tremors, nystagmus, tetany, seizures, altered mental status

• Atrial and ventricular arrhythmias may occur, especially in Pts treated with digoxin.

• ECG: prolonged QT, flattened T waves, prolonged PR interval, wide QRS. AF. Torsade de pointes may occur.

• Electrolyte disturbances: hypokalemia refractory to K replacement, hypocalcemia refractory to calcium replacement (Mg is necessary for parathyroid function)

• FeMg >2% during hypomagnesemia suggest increased renal excretion.

  • FeMg = (Urine Mg/Urine Cr) divided (Sr. Mg x 0.7) / (Sr. Cr) x 100.

Tx:

• Magnesium must be given with extreme caution in patients with renal insufficiency.

• Asymptomatic hypomagnesemia is treated orally:

  • Mag-oxide 400 mg (240 mg elemental magnesium) PO bid x 2 – 4 days.

  • Serum level should be followed closely, as it is redistributed gradually. A rapid rise in Sr. Mg, will promote renal excretion of Mg.

• MgSO4 2 g IVPB (1 g = 96 gm elemental Mg) IV x 15 min.

• Severe hypomagnesemia: Mg replacement for Sr. Mg 1 - 2 mg/dL:

  • 1 g of MgSO4 = 96 mg elemental magnesium

  • If Mg 1.6 – 1.9 mg/dL, give Magnesium sulfate 2 gm IVPB x 1 over 15 minutes.

  • If Mg ≤ 1.5 mg/dL give Magnesium sulfate 2 gm IVPB x 2

• Test DTR frequently, as hyporeflexia suggests hypermagnesemia.

Phosphorous (as phosphate): normal range (2.3 – 5 mg/dL)

• ~ 85% of body phosphorus is in bone, rest in cells, 1% in ECF.

• Best measured in fasting state. Diurnal variation and lowest in morning. -CHO ingestion and glucose IV ↓phos.

• PTH lowers Sr. phos by by decreasing proximal tubular resabsorption of phosphate > urinary wasting.

• Calcitriol (1,25[OH]2 D3) increases serum phosphorus by enhancing intestinal phosphate absorption.

• Insulin ▼ phos by shifting it intracellular.

Hyperphosphatemia

Causes:

• Iatrogenic: Excess phosphate adm. phospho-soda enemas (e.g., Fleet's) given to patient with renal insufficiency failure, excessive intake of PO or IV phosphate

• Decreased renal phosphate excretion: renal insufficiency, hypoparathyroidism, pseudohypoparathyroidism, acromegaly, thyrotoxicosis, biphosphonate therapy, tumor calcinosis, sickle cell anemia

• Extracellular shift: rhabdomyolysis, tumor lysis syndrome, metabolic and resp. acidosis DKA and hyperinsulinemia.

Tx:

• Dietary phosphate restricted to 60-900 mg/day.

• Calcium carbonate 0.5 - 1 gm elemental calcium PO tid with meals. Increase upto max 3 gm tid in 4 wks. Maintain Sr. phos levels 4.5-6 mg/dl. Keep Sr. Ca: <11 mg/dl, and Sr. Ca x Sr. Phos = <60 to minimize risk of ectopic calcification.

• Insulin and D5W infusion promotes intracellular phosphate shift (rapid, but temporary, carries risk of hypokalemia).

• Phoslo (calcium acetate), 667 mg 1 – 3 PO tid w/ meals (watch for Ca levels)

• Amphojel (Aluminum hydroxide), 5 – 10 ml or 1 – 2 tabs up to 6 per day can be given (may cause constipation). Avoid in renal Pts, due to aluminum content.

• Renagel (Sevelamer) 800 – 1600 mg PO tid (use in ESRD). It avoids the complications of hypermagnesemia, hypercalcemia, and aluminum toxicity. It is a non-absorbable cationic polymer that binds phosphate through ion exchange and also lower total cholesterol conc. SE: GI complaints, worsening of metabolic acidosis. Use approved ONLY in pts undergoing DIALYSIS.

• Saline diuresis in acute hyperphosphatemic patients who do not have renal failure.

• Dialysis is not effective due to large intracellular store of phos. Extended or nocturnal HD is only mode of HD that has been shown to lower phosphate levels.

Hypophosphatemia (<2.3 mg/dL)

Si and Sx occur only if Sr. phos level <1 mg/dl.

Causes:

• Impaired intestinal absorption: malabsorption synd, oral phosphate binders, vitamin D def, chronic alcoholism assoc. with ▼ PO intake of phosphate and vitamin D > total body phos depletion.

• Increased renal excretion: associated with ▲ PTH levels and hyperparathyroidism, osmotic diuresis and d/o proximal tubular transport such as familial X-linked hypophosphatemic rickets and Fanconi's synd.

• Transcellular shift: Insulin, resp. alkalosis. Insulin - hyperalimentation in tx of malnutrition > hypophosphatemic refeeding syd.

• Hungry-bone synd: Phosph can be rapidly reabsorbed into bone following parthyroidectomy for severe hyperparthyroidism.

Si & Sx:

• Musculoskeletal: rhabdomyolysis (▼ 2, 3, DPG in RBC > muscle inj), proximal muscle weakness, altered gait, bone pains

• Neurologic: paresthesiae, seizures, coma, ataxia, dysarthrias, confusion

• Hematologic: hemolytic anemia, leukocyte or platelet dysfunction

Dx:

• Exclude presence of glucose/insulin infusions

• Exclude respiratory alkalosis

• Urine phosphate excretion:

  • low (<100 mg/day): GI losses or internal redistribution

  • high (>100 mg/day): Exclude Fanconi's syndrome

• Serum calcium (if Fanconi syndrome has been excluded):

  • High: 1° hyperparathyroidism, hypercalcemia of malignancy

  • Low: 2° hyperparathyroidism, recovery from renal failure, vitamin D resistant rickets, familial hypophosphatemia

• ▲ iPTH = primary or secondary hyperparathyroidism

Tx:

• Acute severe hypophosphatemia (< 1mg/dL). K phos

  • Infusion of phosphate, 0.08 - 0.16 mEq/kg in 500 ml of 0.45% saline, IV x 6 hrs. Slow down infusion rate if hypotension. Stop IV infusions when Sr. phos reaches >1.5 mg/dl. Needs continous infusion over 24 - 36 hours to replinish intracellular stores. Check Sr. phos, and calcium q8 hrs.

  • Avoid hypocalcemia. If hypotension occurs, suspect hypocalcemia and d/c infusion or slow down infusion.

• Chronic hypophosphatemis: Tx vitamin-D deficiency first. F/up elemental phos 0.5 - 1 gm PO bid or tid.

  • Neutraphos (250 mg elemental phos + K: 7 mEq) caps.

    • 2 packets bid (do not give for Pt with CRI/CKD)

  • Kphos 250 mg PO qid or K phos or Na phos 15 mmol IVPB if Sr Phos: <1 (In renal Pts with low phos, DC Renagel and give Neutraphos)

  • Fleet phospho-soda (815 mg phos + 33 mEq Na), 5 mL. Side effect: nausea and vomiting.

• • • • D5W IV, when only H2O needs to be replaced. Each L delivers 1 L of free H20.

      • Check Na q8-12 hrs.