Metabolic alkalemia is difficult to sustain since Kidneys can excrete excess bicarb and correct alkalosis quickly. When there is chloride depletion or hypokalemia, kidneys have decreased ability to excrete the excess bicarb and metabolic alkalemia ensues.
This takes us to the next question!
1) Why does chloride deficient state decreases the ability to excrete excess bicarb?
2) How does hypokalemia contribute to maintaining metabolic alkalosis?
Chloride deficient state increases bicarb reabsorption in proximal tubule and distal tubule(To maintain electro neutrality either chloride or bicarb( two predominant anions) has to be reabsorbed with sodium, so in chloride deficient state bicarb is reabsorbed). Also, in the cortical collecting duct(beta intercalated cell) chloride from the lumen is exchanged for bicarb from inside the cell. In the chloride deficient state, this is limited. I guess, these are good enough reasons for maintaing the alkalosis in chloride deficient states(what ever be the initial pathology that initiated the alkalosis)
Hypokalemia increases ammonia generation in proximal tubule and thereby facilitates acid excretion(even in alkalemic state). Hypokalemia also causes intracellular acidosis(protons exchanged for K trying to mitigate hypokalemia)and extracellular alkalosis. This in proximal tubule will lead to increased acid excretion and bicarb reabsorption. Also, most cases of hypokalemia are associated with hyperaldosteronism (either primary or secondary ) which by itself increases acid excretion by activating H/K pump and also by K excretion in principal cell(in response to Na absorption through ENaC) which inturn is exchanged for proton .
Now we understand that to maintain metabolic alkalosis, there should be either chloride depletion or potassium depletion and it makes much more sense to classify metabolic alkalosis as
1) Metabolic alkalosis secondary to chloride depletion
2) Metabolic alkalosis secondary to potassium depletion
Chloride depletion occurs in vomiting, NG suction, diuretics (chloruretic diuretics in contrast to kaliuretic diuretics)
K depletion occurs in the following conditions
- Primary hyperaldosteronism
- Cushing’s syndrome
- Secondary hyperaldosteronism
- Kaliuretic diuretics
- Excessive licorice intake
- Bartter’s syndrome
Severe potassium depletion
The rest of the causes of metabolic alkalosis are usually not sustainable without chloride deficient state or a potassium deficient state(milk alkali syndrome, persistent bone resorption-where kidneys will step up alkali excretion)
Vomiting, NG suction, Diuretic use, Hyperaldosteronism(primary and secondary) and Severe potassium depletion accounts for 90% of the cases of metabolic alkalosis!
Hope this helps to quickly know the differentials of metabolic alkalosis and to quickly think about the pathogenesis .
Follow up/ 03/17/2014 from commentary section
Dr.Weiner’s lecture today gives us the reason why Hypokalemia in RTA is not associated with increase in ammonia production!. The defect in Type 2 RTA is NBE2 in the basolateral membrane(most likely pathogenesis) . This increases bicarb concentration intracellularly in the proximal tubular cells and thereby the systemic acidosis is masked and the proximal tubular cells spill bicarb in the urine much more than what can be reabsorbed by distal mechanism.
In Type 1 RTA although NH3 production is increased proximally, this has to be reabsorbed in the ascending loop of Henle(NKCl cotransporter is used for ammonia reabsorption) and subsequently this reabsorbed ammonia should be secreted in the distal tubule to help H+ excretion. The defect in H+ ATP prevents NH4 + production. So the net Ammonium production is decreased in type 2 RTA and this contributes to acidosis.