BGOTW #20 – Metabolic Alkalosis Part 2

BGOTW #20

This week is a continuation of the discussion about metabolic alkalosis. If you haven’t already, review last week’s discussion then come back here.

A chloride deficit is the most common maintaining process for human patients with a metabolic alkalosis, and this is probably true for veterinary patients also. Because electroneutrality has to be maintained in the body, chloride is lost with a cation, which means in most cases the patient will lose NaCl, KCl, or HCl. Last week we covered HCl deficit. This week we will look at KCl deficit and NaCl deficit.

 

KCl Deficit

Similar to HCl deficit, KCl deficit results in gain of bicarbonate in the extracellular fluid compartment. Let’s consider a patient on furosemide (a loop diuretic that causes loss of potassium in the urine, and is one of the differentials for a hypochloremic metabolic alkalosis). That patient could have a blood gas that looks very similar to the one we saw in BGOTW #17:

How might this patient have ended up with a metabolic alkalosis? And why is he losing chloride if he isn’t vomiting?  It begins with the patient losing potassium in the urine because of the drugs he is taking (furosemide). The subsequent hypokalemia drives two processes in the kidney that result in the gain of bicarbonate in the extracellular fluid compartment (and thus a metabolic alkalosis).

The cells of the proximal convoluted tubule in the kidney are where we will focus our discussion, but recognize that we are dealing with a total-body potassium depletion.

Potassium ion deficit is associated with acidification of the intracellular fluid compartment of the proximal convoluted tubular cells. This results in two alkalinizing processes:

  1. Enhances excretion of ammonium (NH4+) ions in the urine – and because ammonium is positively charged something negative has to leave with it. That something is chloride ions (here is an easy-to-follow discussion of ammoniagenesis from Cornell’s e-clinpath website, which is a veterinary site; for more in-depth discussion see the articles in PubMed Central linked in the references section).
  2. Retention of organic anions (citrate is a common example), which are subsequently converted to bicarbonate

Let’s tackle #1 first. Intracellular potassium loss means that some other positively-charged ion(s) need to be taken into the cell to maintain electroneutrality. This is going to be both sodium ions and hydrogen ions. As the intracellular space becomes acidified the ‘normal’ rate of ammoniagensis increases. If you need to, review ammoniagenesis using the references of your choice, then come back. The important take-aways from that review are that ammoniagenesis is one of the ways the body gets rid of an acid-load, and the process of ammoniagenesis results in production of one ammonium molecule (NH4+) and 3 bicarbonate molecules.  

The ammonium will be excreted in the urine. Ammonium has a positive charge (NH4+) – it’s loss in the urine must be balanced with loss of a negatively-charged ion to maintain electroneutrality: this will be chloride (Cl-). That’s the source of the chloride loss in these patients.

AND don’t forget about the 3 bicarbonates that were generated when that ammonium was generated. Each of those will link up with a sodium (to maintain electroneutrality) and end up back in the circulating blood volume – this is the ‘gain’ of bicarbonate in the ECF, where the metabolic alkalosis is actually measured.

Next we will tackle #2: retention of organic ions. The alkali load that is consumed as part of the daily diet must be excreted from the body, otherwise a significant metabolic alkalosis would occur. The (very) simplified physiology is: food is consumed and ultimately the organic anions that are part of the diet travel through the portal circulation to the liver where they are converted to bicarbonate (this prevents potentially toxic organic anions from entering the systemic circulation). In response to this ‘alkali load’ the liver makes  organic acids – the hydrogen ions from these acids titrate the bicarbonate from the organic anions that were consumed with the meal. The conjugate-base of these acids is then ultimately secreted (with potassium) by the kidney. The majority of this ‘base’ is excreted in the urine instead of being re-absorbed, thus secreting the dietary alkali load.

In the presence of intracellular acidosis (caused by hypokalemia), these organic anions are reabsorbed instead of being secreted in the urine thus preventing excretion of bicarbonate despite the extracellular alkalosis.

So, KCl deficit causes metabolic alkalosis by both gain of bicarbonate (process #1) and inhibition of bicarbonate/organic anion excretion (process #2).

 

Loss of NaCl

Metabolic alkalosis caused by loss of sodium chloride results in a ‘contraction alkalosis.’ But what does that really mean?

The measurement of bicarbonate that is reported on the blood gas (or chemistry profile) is the concentration of bicarbonate in the extracellular fluid compartment. Within the ECF, bicarbonate is evenly distributed between the intravascular and extravascular compartments, so when we measure the serum or plasma bicarbonate concentration it represents the bicarbonate concentration the ECF. Concentration of bicarbonate is another way of saying the ratio of bicarbonate. In other words the ratio of millimoles of bicarbonate to liters of extracellular fluid  (eg 38mmol/L)

So, the two ways that the bicarbonate can increase are:

  1. the numerator (mmol bicarbonate) increases, OR
  2. the denominator (liters of serum/plasma/extracellular fluid volume) decreases

Loss of sodium chloride will result in ECF volume depletion (where salt goes water follows…):

  • as sodium is lost the ECF volume decreases, therefore the concentration of bicarbonate ions rises (there is less fluid diluting the bicarbonate) resulting in alkalosis.
  • usually vomiting or diarrhea of sodium-containing fluid in veterinary patients

 

Useful References: