Week 37: Endocrine Part I

Acidosis and alkalosis are processes that lead to acidemia (pH < 7.40) and alkalemia (pH > 7.40). Primary metabolic disorders result from a change in bicarbonate, while primary respiratory disorders result from a change in partial pressure of carbon dioxide. Compensation occurs when other system alterations bring the blood gas toward a normal pH of 7.35. A metabolic acidosis is present in any patient with a pH of < 7.35 and bicarbonate < 24. Causes of an increased anion gap acidosis [Na+ - (Cl- + HCO3-)] > 20 can be remembered by the MUDPILES mnemonic (Methanol, Metformin, Uremia, Diabetic (or alcoholic) ketoacidosis, Paraldehyde, Propylene glycol, Isoniazid, Iron, Lactic acidosis, Ethylene glycol, Salicylates). Normal anion gap acidosis is caused by: renal losses (tubular acidosis, acetazolamide), GI losses (diarrhea, malabsorption), and adrenal insufficiency. Compensation for an acid-base disorder never completely normalizes the pH. A pH of 7.45 in a patient with low bicarbonate indicates a second disorder (such as a primary respiratory alkalosis).

Metabolic alkalosis (B) is caused by an increase in bicarbonate leading to a pH > 7.35. This occurs secondary to gastric acid loss from vomiting or NG tube suctioning, diuretic use, and adrenocortical hormone excess. Respiratory acidosis (C) is caused by an increase in the partial pressure of carbon dioxide > 40 leading to a pH < 7.35. This is primarily a result of inadequate ventilation or increased dead space. Causes include head or chest trauma, oversedation, obtundation, neuromuscular disorders, Pickwickian syndrome (obesity-hypoventilation syndrome), and COPD. Respiratory alkalosis (D) is caused by a decrease in the partial pressure of carbon dioxide < 40 leading to a pH > 7.35. In this condition, carbon dioxide ventilation outpaces production.

The patient has a small-bowel obstruction (SBO), most likely due to adhesions that have developed from her multiple abdominal surgeries. The common presentation of SBO includes crampy, poorly localized abdominal pain, vomiting, and abdominal distension. Bowel sounds can be hyperactive initially but become quiet or absent once complete obstruction occurs. Abdominal plain-film findings include air-fluid levels, dilated loops of small bowel above the point of obstruction, and lack of air in the rectum. Dehydration and associated hypokalemia are common. Treatment measures include IV hydration, potassium repletion, nasogastric tube placement, and surgical consultation.

Hypercalcemia (A) can occur with malignancy, hyperparathyroidism, drugs, immobilization, Paget’s disease, or excessive intake (vitamin D toxicity, milk-alkali syndrome). Major clinical findings can be remembered with the phrase “stones, bones, groans, and psychiatric overtones” (nephrolithiasis, weakness, abdominal pain/constipation, confusion/depression). Hypercalcemia shortens the QT interval. Hypocalcemia (B) can be seen in renal failure, hypoparathyroidism, pancreatitis, or chronic malabsorption syndromes. Neurologic symptoms include paraesthesias, carpopedal spasm, Chvostek’s or Trousseau’s sign, and hyperreflexia. Cardiovascular signs include hypotension, heart failure, dysrhythmias, and prolonged QT interval. Hyponatremia (D) can present in a variety of ways, depending on the etiology. The patient can appear dehydrated (hypovolemic hyponatremic) or edematous (hypervolemic hyponatremic), or the fluid status can be normal (syndrome of inappropriate ADH release, psychogenic water drinking, drugs, hypothyroidism).

Hyponatremia is defined as sodium less than 135 mEq/L. Hyponatremia can occur in a hypovolemic, euvolemic, or hypervolemic state. Hypervolemic hypo-osmolar hyponatremia is is associated with fluid overload. The etiology is usually from a perceived low intravascular volume by the kidneys and active water reabsorbtion in excess to sodium retention. If urine sodium is low (<20) causes include liver failure, cirrhosis, hepatorenal syndrome, nephrotic syndrome, and CHF. If urine sodium is high (>20) causes include acute or chronic renal failure, such as that caused by hypertensive nephropathy. Treatment of hypervolemic hypo-osmolar hyponatremia is dialysis.

Cirrhosis (A) and congestive heart failure (B) is often the cause of hypervolemic hypo-osmolar hyponatremia when the urine sodium is low (<20). SIADH (D) results in euvolemic hyponatremia with urine osmolality greater than serum osmolality. The excess ADH causes total body water to increase thereby diluting total body sodium. Despite the increased total body water, these patients typically do not show evidence of edema or heart failure as the increased water is intracellular not intravascular.

This ECG is indicative of hyperkalemia, one of the most lethal complications of chronic kidney disease encountered in the ED. A potassium level of 6 mEq/L should be considered potentially dangerous, even though many patients with ESRD chronically tolerate serum levels above this and do not manifest ECG changes. The most rapid treatment for hyperkalemia is intravenous calcium (gluconate with peripheral access, chloride with central access), which transiently reverses cardiac effects of hyperkalemia by antagonism of potassium at the cardiac membrane. Calcium is indicated in all patients with suspected hyperkalemia who have widening of the QRS, an unstable dysrhythmia, bradycardia, or hypotension.

Cardiology consultation (B) is not needed; the patient’s ECG findings are due to an underlying electrolyte abnormality, not a primary cardiac condition. Defibrillation (C) may be necessary if the rhythm deteriorates to ventricular fibrillation. However, should that occur, the definitive management remains removal of potassium from the serum. Transcutaneous pacing (D) can be used as a temporizing measure in patients with symptomatic bradycardia. Hyperkalemic bradycardia responds poorly to pacing. The primary treatment is cardiac membrane stabilization with calcium and subsequent lowering of the serum potassium.

Hypokalemia frequently occurs concomitantly in patients with hypomagnesemia. Because magnesium is required for the normal functioning of the Na+/ K+ ATPase pump, hypomagnesemia can result in refractory hypokalemia that is not correctable by the administration of potassium alone. For potassium levels to increase, magnesium must also be administered.

Hypermagnesemia (A) enhances potassium retention. Hypernatremia (B) and hyponatremia (D) will not interfere with increasing the level of potassium in patients receiving potassium supplementation for hypokalemia.

D. Correct. Hyperventilation causes a respiratory alkalosis. This in turn increases serum pH and therefore enhances protein binding of calcium in serum. The end result is decreased free ionized calcium. This induced hypocalcemia causes muscle spasm and in severe cases may lead to a tetany like state

A. Incorrect. Decreased PaCO2 causes muscle fiber contraction
Decreased PaCO2 is not the cause of carpal spasm

B. Incorrect. Increased PaO2 causes neuronal activation
Increased PaO2 is not the cause of carpal spasm

C. Incorrect. Increased serum pH causes vasodilation of capillary beds
Hyperventilation would not increase serum pH and is not the cause of carpal spasm

The syndrome of inappropriate secretion of ADH (SIADH) is defined by the secretion of ADH in the absence of an appropriate physiologic stimulus. Its hallmark is an inappropriately concentrated urine, despite the presence of a low serum osmolality and a normal circulating blood volume. Causes of SIADH include central nervous system disorders, pulmonary disease, drugs, stress, pain, and surgery. Therefore, the above patient, with a known history of lung cancer and hyponatremia, most likely has SIADH and exhibits the following lab findings: serum osmolarity low, urine osmolarity high, urine sodium high.

Psychogenic polydipsia (D) is a rare cause of euvolemic hyponatremia and is seen in psychiatric patients who consume large amounts of free water (in excess of 1 L/hr). This large consumption overwhelms the kidney’s ability to excrete free water. Patients will exhibit serum osmolarity low, urine osmolarity low, urine sodium low. Diabetes insipidus (B) results in the loss of large amounts of dilute urine from the loss of concentrating ability in the distal nephron. This may be due to a central cause—such as the lack of ADH secretion from the pituitary—or a nephrogenic cause—such as the lack of responsiveness to circulating ADH. Laboratory workup that invariably shows serum osmolarity high, urine osmolarity high, urine sodium low (A) rarely occurs.

The patient is in an acute metabolic acidosis as is evident by the pH and low bicarbonate. A quick calculation shows that the anion gap is 26 and that the respiratory response with a drop in PaCO2 to 22mmHg follows the “rule of 15’s” with the HCO3 of 8, displaying a proper hyperventilatory response to an acute metabolic acidosis and no evident mixed acid/base disorder. Anion gap is calculated by Na -HCO3 – Cl. For the rule of 15’s, HCO3 + 15 should = the pCO2 and the last 2 digits of the pH. In this patient, 8+15 = 23. This is the correct CO2 indicating an appropriate response. It is also the last 2 digits of the pH (7.23). Thus this is not a mixed acid base disorder but rather an acidosis with appropriate compensation. There are no ketones in the patient’s urine, and the lactate is elevated, thus this patient is in an acute lactic acidosis secondary to metformin rather than DKA.

A. Incorrect. Acute anion gap diabetic ketoacidosis
There are no ketones in the patient’s urine to suggest diabetic ketoacidosis.

C. Incorrect. Acute non-anion gap metabolic acidosis
This patient has an anion gap of 26 which is elevated and consistent with an anion gap acidosis. Recall anion gap is calculated by Na -HCO3 – Cl.

D. Incorrect. Mixed acid/base disorder
This patient has an appropriate compensatory response. Recall the rule of 15’s – HCO3 + 15 should = the pCO2 and the last 2 digits of the pH. In this patient, 8+15 = 23. This is the correct CO2 indicating an appropriate response. It is also the last 2 digits of the pH (7.23). Thus this is not a mixed acid base disorder but rather an acidosis with appropriate compensation.

Congenital adrenal hyperplasia (CAH) is a disorder of steroid synthesis or function. Affected infants typically present between the second and fifth weeks of life; the presentation often is an acute crisis similar to the one described in the case, including hypovolemia and hyponatremia related to the salt wasting. The most common form of the disorder is 21-hydroxylase deficiency, accounting for 90% of cases; it is inherited in a recessive manner. Salt wasting with subsequent clinical manifestations is caused by the altered synthesis of the enzymes involved. Other characteristics due to excess androgen result in virilization that is more obvious in girls and that can lead to a missed diagnosis of a male child at or soon after birth. Although CAH is part of the normal neonatal screening, results might not be available for 3 to 4 weeks. Acute care consists of reversing the shock state as quickly as possible using hydration with isotonic fluids and providing mineralocorticoids using hydrocortisone 50 mg/m2 per day.

B. Incorrect. Pavor nocturnus, otherwise known as night terrors, occurs in older children in the early stages of sleep (within the first 2 hours). Affected children are inconsolable but eventually go back to sleep and have no recollection of the event afterward. Pavor nocturnus can affect up to 20% of children, but incidents occur rarely and decrease with age, so treatment is often not required.

C. Incorrect. Pseudohyponatremia is present in patients with elevated glucose due to a displacement of fluid; it is not present with mild hypoglycemia as seen in this patient. It is often found in a patient in diabetic ketoacidosis. Actual serum sodium can be calculated with the following formula: Sodium + (glucose – 100/100) (for glucose >100 mg/dL).

D. Incorrect. Sepsis must always be considered, regardless of hyperthermia or hypothermia, in the evaluation of a neonate with an alteration from baseline. The abnormal laboratory values in this case are not consistent with this diagnosis, however, making CAH more likely.

Diabetic ketoacidosis can result in severe hypophosphatemia due to metabolic acidosis, osmotic diuresis, and mobilization of intracellular phosphate stores leading to urinary loss. Severe hypophosphatemia leads to impairment of ATP production and inadequate energy metabolism. Clinical manifestations—including myocardial depression, hypotension, and respiratory insufficiency—may be present but typically occur only when serum phosphate levels are significantly diminished (< 1 mg/dL). Other causes of hypophosphatemia include malnutrition, chronic diuretic or antacid therapy, sepsis, and chronic alcoholism.

Hypophosphatemia can result from hyperparathyroidism (B), not hypo-parathyroidism. The high levels of parathyroid hormone that occur with hyperparathyroidism increase renal phosphate excretion. Renal failure (C) may be associated with hypophosphatemia, but renal insufficiency is associated with hyperphosphatemia. Rhabdomyolysis (D) can be induced by hypophosphatemia but does not independently cause it.