Metabolic

11.1 Acidosis

Am J Med Sci 1999;317:38; Post Grad Med J 2000;102:249, 253, 257

Cause: Ketosis from DKA; isopropyl alcohol poisoning; lactic acidosis (Am J Med 1994;97:47)—ethanol intoxication (Hum Exp Toxicol 1996;15:482), septic shock, metformin treatment, hypotension, respiratory failure, liver failure, or short bowel Lactobacillus overgrowth; salicylate; acetaminophen (Ann EM 1999;33:452); ethylene glycol, methanol, isopropyl alcohol, paraldehyde or toluene poisoning; severe diarrhea, D-lactate produced by gut flora, pancreatic fistulas; uremia, RTA; ileal conduit. Non-anion gap in those with asthma secondary to prolonged hypocapnia, not lactic acidosis (Crit Care Med 1987;15:1098).

Crs: In trauma, severity of metabolic acidosis correlates with development of acute lung injury (Crit Care Med 2000;28:125).

Lab: Metabolic profile, ABG (venous pH OK if low suspicion, do ABG if pH < 7.3), salicylates, acetaminophen, ketones, ethanol level, measured vs calculated osmoles, lactate level; Wood’s lamp evaluation of urine to assess for ethylene glycol of variable utility.

Emergency Management:

Address the primary disease.
Treatment with any alkali, even sodium bicarbonate may paradoxically worsen the physiology (Metabolism 1966;15:1011)
even if pH < 7.2 although helpful in “low” (normal) anion gap acidoses, especially if not associated with tissue hypoxia (Brit J Anaesth 1991;67:165).
Dichloroacetate no help in lactic acidosis (Am J Med 1994;97:47).
Tris buffer (Resuscitation 1998;37:161) no help in acidosis, even during CPR.

11.2 Calcium Disorders

Nejm 2000;343:1863; Emerg Med Clin N Am 1989;7:795

Cause:

Hypocalcemia (J Clin Endocrinol Metab 1995;80:1473) seen in hypoparathyroidism due to post-thyroidectomy (Arch Surg 2000;135:142) seen in first 48 hr; spontaneous/sporadic (Am J Med Sci 1989;297:247); acquired through renal failure; pancreatitis; hypomagnesemia—seen post-thyroidectomy (World J Surg 2000;24:722); alcoholism—by hypomagnesemia or direct suppression of PTH; major/minor abdominal surgery (J Clin Endocrinol Metab 1999;84:2654); sepsis (Crit Care Med 2000;28:93); and consuming soft drinks with phosphoric acid, F > M, although this probably has a negligible clinical effect (J Clin Epidem 1999;52:1007).
Hypercalcemia (J Clin Endocrinol Metab 1993;77:1445) seen in hyperparathyroidism via renal calcitriol production (Am Fam Phys 2004;69:333); cancers (Nejm 2005;352:373; Int J Oncol 2000:197)—especially lung, breast, hepatoma; granulomatous diseases—sarcoid, talc granulomas (Chest 2000;117:1195), chronic TB, coccidioidomycosis; Hodgkin’s lymphoma; non-Hodgkin’s lymphoma; cat scratch disease; vitamin D intoxication—including the milk-alkali syndrome (Yale J Biol Med 1996;69:517); immobilization (Clin Orthop 1976:124);
thyrotoxicosis; thiazides—rarely; vitamin A intoxication; benign familial hypocalciuric hypercalcemia—autosomal dominant; and adrenal insufficiency.

Epidem: Hypoparathyroidism associated with Addison’s disease, pernicious anemia, Hashimoto’s thyroiditis, DiGeorge syndrome (3rd and 4th pharyngeal pouches).

Pathophys: For parathyroid physiology, PTH is necessary for an osteoclastic response to low calcium, renal tubular calcium resorption, renal tubular phosphate excretion, and vitamin D activation. Lack of parathyroid glands or PTH results in hypocalcemia and hyperphosphatemia. An ensuing alkalosis is due to blocked PTH stimulation of organic acid production in bones in hypoparathyroidism.

Hypercalcemia may be due to excess PTH or PTH-like proteins—as seen in some T-cell leukemias/lymphomas, secretion of other bone-resorbing substances, tumor conversion of 25-OH vitamin D to 1,25-OH vitamin D (calcitriol), local osteolytic mets, or other causes as seen on the list above.

Sx:

Hypocalcemia: Circumoral paresthesias, carpal-pedal spasms, stridor, seizures—brief and mild, bronchospasm, gi cramps, anxiety, cataracts.
Hypercalcemia: Fatigue, weakness, sleepiness, nausea/anorexia, constipation, polyuria/polydipsia, and volume depletion.

Si:

Hypocalcemia: Tetany (carpal-pedal spasm, Chvostek’s sign, which is facial muscle twitiching from tapping on the facial nerve, and Trousseau’s sign, which is carpal spasm after inflating BP cuff on upper arm), hyperreflexia, cataracts, ophthalmoplegia (Am J Emerg Med 1999;17:105), vascular corneal opacities, psychiatric changes, dystonias, and dyskinesias.
Hypercalcemia: Confusion, delirium, drowsiness, coma.

Cmplc: Patients with hypoparathyroidism may have pustular psoriasis and dermatitis herpetiformis. Patients with hypercalcemia at increased risk for pancreatitis and digoxin toxicity, commonly untreated in patients with cancer (J Intern Med 2001;250:73).

Lab: Metabolic profile to include calcium, albumin, magnesium and phosphate, TSH, amylase, lipase; consider ABG; EKG—special attention to QT interval (J Peds 2000;136:404; J Clin Psychopharmacol 2000;20:260); urine for calcium in hypocalcemia.

Emergency Management:

Hypocalcemia:

1st: vitamin D₃ 50,000-100,000+ U each day; or 1,25-(OH)₂ vitamin D (Rocaltrol), expensive; narrow margins of safety for hypercalcemia.
2nd: Calcium po or iv; Calcium gluconate 10% 10 cc iv or calcium chloride 10% 5 cc iv—repeat PRN every 5 min.
3rd: Chlorthalidone 50 mg po qd or other thiazide, with low-salt diet, voids renal stones of vitamin D treatment.

Experimental use of synthetic PTH.

Hypercalcemia:

Acute treatment for Ca > 13 mg%:

Normal saline 2.5-4 L/24 h iv to ensure intravascular volume adequately replaced (CVP or Swann-Ganz monitoring), avoid furosemide initially, but often needed after volume replaced to prevent volume overload and accelerate renal clearance.
Pamidronate (Aredia) 60-90 mg iv over 24 hr, or 4-8 mg/hr.

Chronic treatment:

Biphosphonates, eg, pamidronate (Aredia) 60-90 mg iv infusion over 8-24 hr or 1200 mg po qd × 5 d.
Steroids primarily for sarcoid patients, eg, prednisone 20 mg po tid or iv 3-4 d.
Calcitonin 4 U/kg q 6 hr sc or im, relatively weak agent alone.
Indomethacin (rarely helpful if due to cancer).
Gallium nitrate iv infusion, experimental 200 mg/M² in 1 L continuous infusion qd × 5 d.

11.3 Magnesium Disorders

Emerg Med Clin N Am 1989;7:795; Can Med Assoc J 1985;132:360

Cause:

Hypomagnesemia seen with gi fluid and electrolyte loss treated with Magnesium-free fluids; malnutrition; diabetes mellitus (Arch IM 1996;156:1143); fistulae; burns; diuretics; cisplatinum-induced renal disease; cyclosporine use in transplant recipients (J Am Coll Cardiol 1992;20:806), and commonly associated with hypokalemia (Clin Chem 1983;29:178), hypophosphatemia, hyponatremia, and hypocalcemia (Arch IM 1984;144:1794).
Hypermagnesemia seen in renal failure often parallels potassium; chronic Magnesium containing antacid and laxative use (Ann Emerg Med 1996;28:552). Enemas, especially in megacolon, with Magnesium-containing soaps.