Hypokalaemia

What it is

Hypokalemia is a fall in the serum potassium. Its mark on the ECG is the U wave, and correcting it depends on the magnesium as much as on the potassium given.

Causes and risk

The selected causes fall into two groups. Increased renal losses come from diuretics and from type I and type II RTA, and increased GI losses come from vomiting and diarrhea. Raised insulin, a beta agonist and alkalosis are also given as causes of hypokalemia.

Excess aldosterone is the group to think of when the blood pressure is high. Conn syndrome, or primary hyperaldosteronism, comes from an aldosterone-producing adrenal adenoma or hyperplasia and is usually sporadic. Liddle syndrome comes from a gain-of-function mutation in ENaC and is autosomal dominant.

Two further causes are named. A VIPoma gives the WDHA picture, watery diarrhea with hypokalemia and achlorhydria, with a metabolic acidosis. Fanconi syndrome, a generalized dysfunction of the proximal tubule, loses glucose, amino acids, phosphate, bicarbonate, uric acid and potassium into the urine, giving hypokalemia with hypophosphatemia and a non-anion gap metabolic acidosis. Its inherited forms are cystinosis, the most common in children, Wilson disease, galactosemia and the glycogen storage diseases; its acquired forms are drugs, that is ifosfamide, tenofovir, cisplatin and outdated tetracyclines, along with multiple myeloma and heavy metal toxicity from lead and cadmium.

One way to hold the causes is to split them by the blood pressure. Hypokalaemia with hypertension: Cushing's syndrome, Conn's syndrome, that is primary hyperaldosteronism, Liddle's syndrome, and 11-beta hydroxylase deficiency; and carbenoxolone, an anti-ulcer drug, and liquorice excess can potentially cause hypokalaemia associated with hypertension. Hypokalaemia without hypertension: diuretics, GI loss such as diarrhoea and vomiting, renal tubular acidosis of type 1 and 2, Bartter's syndrome and Gitelman syndrome. Two notes go with that split: 21-hydroxylase deficiency, which accounts for 90% of congenital adrenal hyperplasia cases, is not associated with hypertension, and type 4 renal tubular acidosis is associated with hyperkalaemia instead.

The two tubular syndromes are told apart feature by feature. Gitelman syndrome is in the distal convoluted tubule, from a mutation in SLC12A3, the thiazide-sensitive Na-Cl cotransporter; Bartter syndrome is in the thick ascending limb of the loop of Henle, from mutations in SLC12A1, the Na-K-2Cl cotransporter, KCNJ1 which is ROMK, or CLCNKB the chloride channel. Gitelman gives hypokalemia with hypomagnesemia and hypocalciuria; Bartter gives hypokalemia with hypochloremia and hypercalciuria. The blood pressure is normal in Gitelman, while some forms of Bartter have hypertension from hyperaldosteronism. Renin and aldosterone are normal in Gitelman and elevated in Bartter. Gitelman appears in late childhood to early adulthood, Bartter in early childhood, and neonatally in severe forms. Both give a metabolic alkalosis, from potassium wasting in Gitelman and from potassium and chloride wasting in Bartter. Growth is normal in Gitelman and retarded in Bartter.