Blood Gas of the Week #19 – Metabolic Alkalosis Part 1
Last week we looked at using the delta gap and delta ratio to assess a high-anion gap metabolic acidosis. This week we are going to continue the in-depth look at acid-base analysis, this time focusing on metabolic alkalosis. This is a big topic so it will be covered in multiple parts. This series of posts will look at how a metabolic alkalosis occurs, how the alkalosis is maintained, the clinical implications of a metabolic alkalosis, and approaches to treatment. For the discussion we will refer back to BGOTW #17. If you haven’t worked through that case yet, go here and take a few minutes to be sure you understand how we came to the diagnosis of metabolic alkalosis. Then come back here to continue with the discussion.
Metabolic Alkalosis: “Inciting Events” and “Maintenance Abnormalities”
In order for a patient to have a persistent metabolic alkalosis TWO ‘problems’ have to occur: first the patient has to develop a problem or condition that causes a metabolic alkalosis, and then a second problem that maintains the metabolic alkalosis. All the ‘problems’ are associated with significant electrolyte derangements. For that reason, many have suggested to think about metabolic alkalosis as mainly a disorder of electrolytes that is accompanied by an increase in the number of bicarbonate molecules and the pH of the extracellular fluid.
Causes of Metabolic Alkalosis
The mnemonic GROE is helpful for remembering the broad causes of metabolic alkalosis
Gastrointestinal (GI) loss of acid and fluid
Vomiting, particularly from a pyloric outflow obstruction
Pyloric/gastric foreign body, pyloric mass or stenosis, extraluminal mass compressing pylorus, etc
Diarrhea (usually protracted and severe to cause a clinically significant metabolic alkalosis in veterinary patients)
Dehydration (‘contraction alkalosis’)
Renal loss of acid
Diuretics (loss of Hydrogen, potassium, & chloride ions in particular)
(there are also some very rare inherited disorders discussed in people – even less common in dogs/cats)
Overdose of base
Iatrogenic (Bicarbonate administration)
Antacid OD (chewing up the box/bottle, or owner administration)
Laxative administration (both from the drug and the diarrhea)
Endocrine causes
Steroid excess (iatrogenic, Cushing’s disease)
Hyperaldosteronism
Maintenance Processes/Abnormalities
Maintenance of an alkalosis requires some process that prevents the kidneys from reducing the plasma bicarbonate level. This gives us two ‘classes’ of problems: either bicarbonate isn’t being filtered at the glomerulus, or something is increasing bicarbonate resorption in the tubules.
Not filtered at the glomerulus
ECF volume depletion (AKA volume contraction, which actually might be chloride depletion alkalosis)
Reduced GFR
Increasing bicarbonate resorption in the tubules
Chloride depletion
Potassium depletion
Mineralocorticoid excess
Generation and maintenance of a hypochloremic metabolic alkalosis
A chloride deficit is the most common cause of metabolic alkalosis for human patients 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. Loss of sodium chloride will result in ECF volume depletion (as sodium is lost the ECF volume decreases, this is a topic for another post). Loss of KCl or HCl will result in a gain of bicarbonate.
Our patient in BGOTW #17 was vomiting resulting in a hypochloremic metabolic alkalosis, so we will start with HCl losses.
First, where does the acid (hydrogen ion) come from? This part should be easy if you have been following BGOTW for a while: it’s all about the carbonic anhydrase equation. The process of converting carbon dioxide and water to hydrogen ions and bicarbonate isn’t just for buffering in the ECF. It is happening all over the body to power many different processes. A quick review:
Carbon dioxide and water are present in the cell (and the ECF, but right now we are talking about what is happening in the vomiting dog). The enzyme carbonic anhydrase catalyzes their conversion to carbonic acid. Carbonic acid dissociates to form hydrogen ions, and bicarbonate. This is the process by which acid is buffered in the extracellular fluid. It is also the process that allows parietal cells in the stomach to secrete acid into the lumen of the stomach, in the from of hydrogen protons:
The stylized drawing above depicts the stomach on the left and a parietal cell on the right. Parietal cells actively secrete hydrogen ions into the lumen of the stomach. Carbon dioxide and water are able to enter the parietal cell. Inside the cell carbonic anhydrase catalyzes conversion to carbonic acid, which then dissociates (as we just discussed above) into a hydrogen ion and a bicarbonate molecule.
The hydrogen ion is secreted into the lumen of the stomach to lower the pH. Because the body must observe the law of electroneutrality, a chloride ion also moves from the intracellular space to the lumen of the stomach. So the cell lost one positively and one negatively charged ion – electroneutrality is preserved. BUT, because one chloride ion has left the intracellular space, another chloride must enter because of the concentration gradient of chloride. So, one chloride from the extracellular fluid moves into the intracellular space. In order to make up for this negatively charged ion entering the cell, a bicarbonate is removed from the cell, into the extracellular fluid. This bicarbonate movement into the ECF when a hydrogen is excreted into the stomach is responsible for the ‘alkaline tide’ – a mild metabolic alkalosis that is seen immediately following a meal.
In a normal, healthy animal, the HCl secreted into the stomach would pass through the pylorus and be reabsorbed further down in the GI tract. So theoretically, the H+ that is reabsorbed in the bowel would be buffered by the bicarbonate that was kicked out of the parietal cell when the hydrogen ion was secreted into the stomach (it won’t be the same bicarbonate molecule, but the concept is important). Likewise the chloride in the stomach acid would also be reabsorbed in the intestine and would enter the extracellular fluid compartment, balancing out the chloride that was moved into the parietal cell to take the place of the one secreted into the stomach. It’s a giant circle of recycling.
But the patient we are discussing from BGOTW #17 had a mass causing a pyloric outflow obstruction – basically none of the stomach contents were entering the intestines to be reabsorbed. Instead he was vomiting it all out. The ‘recycling’ of the ions secreted into the stomach can’t happen. Since the recycling can’t happen, there is a net loss of chloride and gain of bicarbonate in the extracellular fluid compartment (the compartment where we collect our blood samples, which is how we measure the various ions and molecules):
The extracellular compartment loses a chloride when a chloride ion moves into the cell to balance the chloride ion that was secreted into the stomach. Likewise the bicarbonate that is moved from the cell to the ECF to balance the inward movement of chloride is the source of bicarbonate gain in a vomiting patient.
Intuitively many of us like to think about the vomiting patient with metabolic alkalosis as ‘losing acid.’ That’s fine if it helps you remember the pattern for clinical diagnosis (it helps me) – particularly since it should be obvious that to resolve the alkalosis we have to resolve the cause (vomiting). BUT, don’t forget that the metabolic alkalosis in this scenario is technically a gain of bicarbonate. Remembering this (a very common cause of metabolic alkalosis in dogs and cats) will help when your patient isn’t vomiting, and you need to look for other causes of the metabolic alkalosis.
Next week we will continue the discussion looking at KCl losses (another gain of bicarbonate metabolic alkalosis), followed by NaCl losses (a contraction alkalosis).
References & Additional Resources
Hopper et al 2013. Incidence, nature, and etiology of metabolic alkalosis in dogs and cats (PMID 23751002)
Fluid, Electrolyte and Acid-Base Physiology: A Problem-Based Approach
It is Chloride Depletion Alkalosis, not Contraction Alkalosis (PMID 22223876)
