A 52 year old female presents with difficulty walking and weakness.
Her blood results show:moderate to severe metabolic alkalosis with severe hypokalaemia. There is inadequate respiratory compensation.
The metabolic alkalosis is likely secondary to renal retention of HCO3
Compensatory mechanism for this is hypoventilation – here the pCO2 is 46, which indicates partial compensation (bearing in mind this is a venous gas) – expected pCO2 would be around 50 with a normal pH for full compensation. Each 1 mmol increase in HCO3 should cause an increase in CO2 of 0.5-0.7 (limited by central response to increasing CO2).
Causes include:
Dehydration
Endocrine – Conn’s, Cushings
Vomiting – no history here
Excess HCO3 ingestion – no history here
RTA – Barter’s, Gitelman’s
diuretic abuse – possible here
Hypokalaemic periodic paralysis – Na channel / Ca channel defect or even thyrotoxicosis (more likely in older patients)
Many of the causes of metabolic alkalosis are also associated with hypokalaemia. In turn, hypokalaemia maintains metabolic alkalosis by five different mechanisms.
First, hypokalaemia results in the shift of hydrogen ions intracellularly. The resulting intracellular acidosis enhances bicarbonate reabsorption in the collecting duct.
Second, hypokalaemia stimulates the apical H+/K+ ATPase in the collecting duct. Increased activity of this ATPase leads to potassium ion reabsorption but a corresponding hydrogen ion secretion. This leads to a net gain of bicarbonate, maintaining systemic alkalosis.
Third, hypokalaemia stimulates renal ammonia genesis, reabsorption, and secretion. Ammonium ions (NH4+) are produced in the proximal tubule from the metabolism of glutamine. During this process, alpha-ketoglutarate is produced, the metabolism of which generates bicarbonate that is returned to the systemic circulation. Hypokalemia stimulates NH4+ uptake via the Na+/K+/2Cl– cotransporter of TAL because NH4+ competes with K+ for the transporter. Hypokalaemia increases the expression of the ammonia transporter RhBG, which increases NH3 excretion in the collecting duct.
Fourth, it leads to impaired chloride ion reabsorption in the distal nephron. This results in an increase in luminal electronegativity, with subsequent enhancement of hydrogen ion secretion.
Fifth, it reduces the glomerular filtration rate (GFR). Animal studies have shown that hypokalaemia, by unknown mechanisms, decreases GFR, which decreases the filtered load of bicarbonate. In the presence of volume depletion, this impairs renal excretion of the excess bicarbonate.
Treatment:
Replace K
ECG monitoring
Hypokalaemic periodic paralysis:
During attacks, oral potassium supplementation is preferable to IV supplementation. The latter is reserved for patients who are nauseated or unable to swallow. Potassium chloride is the preferred agent for an acute attack (assuming a normal renal function). A reasonable initial dose for a 60-120 kg man (ie, 0.5-1 mEq/kg) is 60 mEq.
Aqueous potassium is favoured for quicker results. If there is no response in 30 minutes, an additional 0.3 mEq/kg may be given. This should be repeated up to 100 mEq of potassium. Beyond this, monitoring of serum potassium is warranted prior to further supplementation.
Typically, one should not exceed a total dose of 200 mEq in a day.
Intravenous potassium is reserved for cardiac arrhythmia or airway compromise due to ictal dysphagia or accessory respiratory muscle paralysis. IV potassium chloride 0.05-0.1 mEq/kg body weight in 5% Mannitol as a bolus is preferable to continuous infusion. Mannitol should be used as solvent, as both sodium and dextrose worsen the attack.
Only 10 mEq at a time should be infused with intervals of 20-60 minutes, unless in situations of cardiac arrhythmia or respiratory compromise. This is to avoid hyperkalaemia at the end of an attack with shift of potassium from intracellular compartment into the blood. Continuous ECG monitoring and sequential serum potassium measurements are mandatory.
Typically, 40-60 mEq of K+ raises the potassium concentration by 1.0-1.5 mEq/L, and 135-160 mEq of K+ raises plasma potassium by 2.5-3.5 mEq/L.
Thyrotoxic
Control thyrotoxicosis and beta-blocking agents.
Potassium supplementation, dichlorphenamide, propranolol, and spironolactone may be helpful during the attacks as well as for prophylaxis. Dichlorphenamide 50-100 mg BID or propranolol in doses of 20-40 mg twice a day may be sufficient to control recurrent attacks of periodic paralysis.
