The cause of hypokalemia is often apparent from the history. Measurements of BP and urinary potassium excretion, and assessment of acid-base balance are often helpful when the cause is not apparent. 
Algorithm to determine the cause of hypokalemia
Courtesy of Dr Udaya Kabadi
Nonsevere hypokalemia is frequently asymptomatic. Common acute manifestations are muscle weakness and ECG changes. More prolonged and profound hypokalemia may cause rhabdomyolysis, renal abnormalities, and cardiac arrhythmias. There are some reports of cases presenting as asymmetric or focal weakness. 
Causes that may be identified from the history and exam include the following:
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.
There is no strict correlation between the serum potassium concentration and total body potassium stores. In chronic hypokalemia, a potassium deficit of 200 to 400 mmol (200 to 400 mEq) is required to lower the serum potassium concentration by 1 mmol/L (1 mEq/L).  These estimates are good provided there is no concurrent acid-base abnormality (e.g., for diabetic ketoacidosis or severe nonketotic hyperglycemia).
In diabetic ketoacidosis patients may have a normal or even elevated serum potassium concentration at presentation, despite having a marked potassium deficit due to urinary and GI losses. 
Spurious hypokalemia can occur when blood with a high WBC count is left at room temperature due to extraction of potassium by the WBCs. It is therefore important to consider repeating the test for confirmation.
Typical laboratory studies include the following:
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.
Subsequent tests (performed depending on the clinical findings)
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.
An ECG is recommended for all patients with hypokalemia. Typically, there is depression of the ST segment, decrease in the amplitude of the T wave, and an increase in the amplitude of U waves (often seen in the lateral precordial leads V4 to V6).Image 2 A variety of arrhythmias may be associated with hypokalemia, including sinus bradycardia, premature atrial and ventricular beats, paroxysmal atrial or junctional tachycardia, atrioventricular block, ventricular tachycardia, or fibrillation. 
ABG analysis revealing metabolic acidosis, in conjunction with a low rate of potassium excretion, suggests lower GI potassium losses due to laxative abuse, a villous adenoma, or GI endocrinopathies such as vasoactive intestinal peptide secreting tumor (VIPoma). 
Metabolic acidosis with potassium wasting is most often due to diabetic ketoacidosis or type 1 (distal) or type 2 (proximal) renal tubular acidosis. A salt-wasting nephropathy may also produce similar findings.
This can occur due to surreptitious vomiting or diuretic use. Some patients with laxative abuse present with metabolic alkalosis, rather than the expected metabolic acidosis.   The alkalosis is due to hypokalemia impairing the intestinal reabsorption of chloride, leading to a diminished bicarbonate secretion into the intestinal lumen via chloride-bicarbonate exchange. 
Metabolic alkalosis with potassium wasting and a normal BP is most often due to surreptitious vomiting, diuretic use, or Bartter syndrome. In this setting, measurement of the urine chloride (rather than urine potassium) concentration is often helpful. Urine chloride is low (<15 mEq/L) in vomiting due to the need to maintain electroneutrality while some of the excess bicarbonate is being excreted. Low urinary chloride due to bicarbonaturia can be differentiated from other causes of low urinary chloride by measuring urine pH; the urinary pH should be more than 7.0 if significant bicarbonaturia is present.
Metabolic alkalosis with potassium wasting and HTN is suggestive of surreptitious diuretic therapy in a patient with underlying HTN, or renovascular disease, or it may be due to a cause resulting in mineralocorticoid excess. The presence of primary mineralocorticoid excess should be suspected in any patient with the triad of HTN, unexplained hypokalemia, and metabolic alkalosis.
Hypokalemic periodic paralysis is suspected with a family history of the disorder, onset following a ingestion of a meal with high CHO content, ingestion of large quantity of simple sugar, during or immediately after a strenuous exercise, in the early morning or in the presence of manifestations of hyperthyroidism.