Metabolic Alkalosis

Recently, we have had two patients in the ICU with metabolic alkalosis.  It can cause depressed consciousness and generalized seizures as well as decrease tissue oxygen availability (by decreasing cardiac output, shifting the oxyhemoglobin dissociation curve to the left, and increasing the glycolysis rate causing increased O2 tissue consumption); therefore, it remains important to understand its causes, workup, and treatment.   

The key word association with metabolic alkalosis is CHLORIDE, CHLORIDE, URINE CHLORIDE.  

MECHANISMS

There are 2 renal mechanisms of acid-base control -- bicarbonate reabsorption in the proximal tubules and hydrogen ion secretion in the distal tubules.   Hydrogen ions are released into the proximal tubules by a sodium hydrogen transporter protein. The hydrogen reacts with bicarbonate to form carbonic acid which dissociates into carbon dioxide and water.  The carbon dioxide moves into the extracellular space to make bicarbonate and hydrogen (via carbonic anhydrase).  For every bicarbonate molecule reabsorbed, one molecule of chloride must move into the renal tubule.  Hydrogen is secreted through the sodium-hydrogen-potassium pump (which is aldosterone sensitive!).  As hydrogen and potassium are secreted into the renal tubules, chloride is moved into the bloodstream while bicarb is moved into the tubule. 

CAUSES

There are many reasons for bicarbonate reabsorption and hydrogen secretion causing metabolic alkalosis.  

Vomiting -- gastric secretions are rich in hydrogen and chloride ions. The chloride depletion stimulates bicarbonate reabsorption, molecule for molecule to maintain electrical neutrality. Emesis also leads to hypovolemia and hypokalemia

Hypovolemia -- an increase in sodium reabsorption in response to volume depletion also leads to bicarb reabsorption. Hypovolemia also stimulates renin which promotes aldosterone (hydrogen secretion!).  

Hypokalemia -- associated with hydrogen secretion

Diuretics (loop and thiazide) -- as sodium is lost in the urine, chloride, magnesium and potassium must follow.

Blood transfusions -- after 8 units of blood, citrate can cause metabolic alkalosis

WORKUP

Again, URINE chloride determines treatment.  Metabolic alkalosis can be chloride-responsive (uCL < 15 mEQ/L or chloride resistant (uCL > 25 mEQ/L).  

TREATMENT

Chloride-responsive can be due to emesis, diuretics, volume depletion, and hypercapnia. Treatment for volume depletion involves isotonic saline infusion (0.9% NaCl).  The amount of fluid needed to correct the deficit is the Chloride deficit/154.  The Chloride deficit (mEQ) = 0.2 x wt(kg) x (normal Cl - actual Cl). 0.1 HCl infusion is also possible by calculating the hydrogen deficit which = 0.5 x wt(kg) x (actual HCO3 - desired HCO3). However, the solution is corrosive to tissue, vein, and even central lines!  Gastric acid suppression (with H2 blocker or PPI) can also help, though sodium chloride losses will be substituted for HCl losses, so chloride depletion continues anyway!

Chloride-resistant can be due to potassium depletion and mineralocorticoid excess (hyperadrenalism, heart failure, etc).  The reasons for this can be seen above!  Potassium must be aggressively corrected as well as the underlying cause of mineralocorticoid excess.  Also, acetazolamide blocks HCO3 reabsorption in the kidneys by inhibiting carbonic anhydrase (see above!).  Bicarb is lost in the urine along with sodium, which helps with diuresis (these patients are often times volume overloaded). 

Remember CHLORIDE, CHLORIDE, URINE CHLORIDE!

 

Thanks to Dr. Amina Merchant for this post!