- Known causative medications include diuretics, corticosteroids, beta-2 agonists (such as albuterol or terbutaline to prevent premature labor or to treat asthma), amphotericin B, chloroquine or theophylline intoxification, vitamin B12 or folic acid administered in megaloblastic anemia, and granulocyte-macrophage colony-stimulating factor (GM-CSF) administered in neutropenia. Other treatments that can produce hypokalemia include dialysis and plasmapheresis.
- Laxative or bowel-cleansing agent abuse. This should be suspected if there is a history of an eating disorder. Associated features include loose stools, colicky abdominal pain, and dizziness.
- A history of chronic alcohol intake should prompt suspicion of alcoholism.
- A history of licorice ingestion should be sought.
- A history of vomiting, diarrhea, nasogastric suction, or an eating disorder indicates GI losses. Patients with an ileal loop/conduit with ureteric implants may also have GI losses. Rarely, a history of colon polyps, hematochezia, diarrhea, constipation, and flatulence may be present, prompting suspicion of a villous adenoma. A clinical syndrome of abdominal pain, flushing, lethargy, nausea, vomiting, muscle weakness, and muscle cramps, associated with weight loss and an abdominal mass, should prompt suspicion of a VIPoma.
- In asymptomatic patients, renal tubular acidosis (RTA) should be considered. Hypokalemia is seen in classic distal RTA and proximal distal RTA.
- The presence of growth retardation in children should also prompt suspicion of RTA.
- Volume depletion indicated by dry mucus membranes and poor skin turgor is most likely to be due to severe diarrhea or to diabetic complications.
- Kussmaul breathing suggests severe metabolic acidosis with respiratory compensation.
- A history of diabetes should prompt suspicion of diabetic ketoacidosis or nonketotic hyperglycemia. These patients may be hyperkalemic initially, and hypokalemia appears following the initiation of insulin treatment. A history of polyuria, fatigue, weight loss, and nocturia followed by rapid deterioration in clinical state with nausea, abdominal pain, and vomiting suggests diabetic ketoacidosis. There may be a history of intercurrent illness or nonadherence with insulin therapy. The onset of nonketotic hyperglycemia is more insidious. Patients are generally older and are usually patients with type 2 diabetes. Mental obtundation and coma are more frequent. Focal neurologic signs (hemianopia and hemiparesis) and seizures are also seen.
- The presence of polyuria alone may indicate central diabetes insipidus.
- If the patient is critically ill, hypokalemia may be the result of a stress response.
- Hypothermia may produce hypokalemia that is reversible on rewarming.
- A history of prolonged treatment with glucocorticoids and/or manifestations of Cushing syndrome suggests glucocorticoid excess.
- The presence of edema or hypertension may indicate circulating mineralocorticoid excess with renal potassium loss.
- Hypokalemia during the neonatal period or childhood and adolescence may suggest the presence of congenital disorders.
- Episodes of muscle weakness or paralysis precipitated by exercise, stress, or an excessively large carbohydrate meal suggest hypokalemic periodic paralysis. Episodes may also be triggered by increased release of epinephrine, cortisol, aldosterone, or insulin and should be suspected in patients with a known history of endocrine disorders that cause hypersecretion of these hormones.
- Involvement of a large area of the skin by burns, psoriasis, or eczema can sometimes be a cause of hypokalemia.
- Patients with known Sjogren disease or systemic lupus erythematosus may have renal disease with potassium loss.
- Persistent pulmonary infections, insatiable appetite, large numbers of stools, or bulky, greasy stools suggest cystic fibrosis.
- A history of psychosis, antipsychotic medication usage, and polyuria should prompt suspicion of primary polydipsia. This is often psychogenic.
Serum potassium concentrations
- Basic metabolic panel (includes serum sodium, potassium, glucose, chloride, bicarbonate, BUN, and creatinine).
- Urine electrolytes (potassium and chloride): useful in differentiating renal from nonrenal causes of hypokalemia when the etiology of the hypokalemia is not readily apparent.
- Arterial blood gas (ABG) analysis; should be performed to detect metabolic acidosis or alkalosis when the underlying cause is not apparent from the history.
- Further urinalysis and urine pH measurement to assess for the presence of renal tubular acidosis.
- Serum magnesium, calcium, and/or phosphorus levels to exclude associated electrolyte abnormalities, especially if alcoholism is suspected.
- Urinary calcium excretion to exclude Bartter syndrome. Clinical features of this syndrome include polyuria and polydipsia associated with growth and mental retardation and either normotension or hypotension. Some patients can also have sensorineural deafness.
- Serum digoxin level if the patient is on digitalis.
- Plasma aldosterone and plasma renin level in patients who have unexplained hypokalemia, especially if it is persistent or resistant to therapy, or if specific renal potassium wasting diseases are suspected such as Bartter, Gitelman, or Liddle syndromes.
- Aldosterone suppression test if aldosterone-producing adrenal adenoma is suspected.
- Urinary free cortisol level, low-dose dexamethasone suppression test, evening salivary cortisol levels, and dexamethasone-corticotrophin-releasing hormone test if there are clinical features of Cushing syndrome.
- A CT scan of the adrenal glands if there is a suspicion of mineralocorticoid, glucocorticoid, or catecholamine excess or MRI of pituitary gland to exclude Cushing disease.
- An abdominal CT scan should be performed if clinical features of VIPoma are present; if the CT is inconclusive it may be necessary to perform radiolabeled pentetreotide scintigraphy or endoscopic ultrasound to confirm the diagnosis.
- Stool osmolality and stool osmolar gap if VIPoma is suspected.
- TSH level is required if there is a clinical suspicion of hypokalemic periodic paralysis.
- Water restriction test is required if central diabetes insipidus or primary polydipsia is suspected.
- Sweat chloride test is required if cystic fibrosis is suspected.
Hypokalemia with metabolic alkalosis
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