Approach to metabolic alkalosis: Clinical sciences

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Introduction0:00–0:36

Metabolic alkalosis refers to an increase in serum bicarbonate concentration, either due to the loss of hydrogen ions from the body or the gain of bicarbonate itself.
This can cause the arterial pH to rise above 7.45, and the serum bicarbonate above 27 milliequivalents per liter. As a reference bicarbonates normally range from 22 to 27 miliequivalents per liter.
Common causes include prolonged vomiting, hypovolemia, diuretic use, and hypokalemia. If a patient presents with a chief concern suggesting metabolic alkalosis, first perform an ABCDE assessment to determine if they are stable or unstable.

Unstable Patient0:36–1:18

If your patient is unstable, stabilize their airway, breathing, and circulation; obtain IV access and put them on continuous vital sign monitoring.
Also, provide supplemental oxygen, if needed. Here’s a clinical pearl!
Patients with severe metabolic alkalosis, meaning pH over 7.6 sometimes require urgent correction of blood pH with hemodialysis, especially if there is volume overload or renal dysfunction.

Stable Patient1:18–3:17

Let’s move on to stable patients. After the ABCDE assessment, obtain a focused history and physical examination; and order labs, including an arterial blood gas analysis or ABG, and CMP.
The history may reveal vomiting or use of loop or thiazide diuretics. Alkalosis increases the protein binding of ionized calcium, so you might find headaches, lethargy, neuromuscular excitability, delirium, tetany, and seizures.
Additionally, alkalemia lowers the threshold for anginal symptoms and arrhythmias. Lastly, if there is hypokalemia, the patient might report weakness.
The physical exam might show signs of dehydration, like dry mucous membranes, and decreased skin turgor. As for the labs, ABG typically shows an arterial pH above 7.45, while CMP reveals elevated serum bicarbonate, often above 27 milliequivalents per liter.
If you see these findings in history, physical exams and labs, that’s metabolic alkalosis. Here’s a clinical pearl!
Metabolic alkalosis can sometimes coexist with un acid-base disorders, making it hard to identify. To figure this out, you need to check the partial pressure of carbon dioxide or pCO2 on the ABG.
If the pCO2 is above the reference range, it might be due to respiratory compensation, or it could mean that metabolic alkalosis and respiratory acidosis are occurring at the same time.
Keep in mind that in chronic metabolic acidosis, pCO2 should increase by about 5 millimeters of mercury for every 10 milliequivalents per liter increase in bicarbonates.
On the other hand, if the pCO2 is below the reference range, metabolic alkalosis might be associated with a coexisting respiratory alkalosis.
Now that you’ve diagnosed metabolic alkalosis, let’s assess for exogenous causes. First up is milk-alkali syndrome.

Exogenous causes3:17–5:02

Milk-akali is characterized by hypercalcemia, renal insufficiency, and metabolic alkalosis. Hypercalcemia often results from ingestion of excessive amounts of calcium, either as supplements or calcium-based antacids.
If it’s not addressed, hypercalcemia can cause renal insufficiency, where the kidney’s ability to excrete bicarbonate is impaired.
Consequently, serum bicarbonate levels increase, leading to metabolic alkalosis. Patients usually have a history of excessive calcium supplementation, or the use of absorbable antacids, like calcium carbonate or sodium bicarbonate.
The CMP often shows elevated serum calcium, BUN, and creatinine levels. If you see these findings, diagnose milk-alkali syndrome.
Next, there’s bicarbonate administration. These patients present with a recent history of large-volume alkaline fluid infusion, such as IV sodium bicarbonate, usually to treat acidosis.
In this case, bicarbonate administration is the cause of metabolic alkalosis. Here’s another clinical pearl!
In individuals with normal kidney function, the ingestion or administration of alkali results in only transient metabolic alkalosis.
Normally functioning kidneys will quickly increase bicarbonate excretion to restore the pH balance. However, in individuals with kidney dysfunction, the effective elimination of excess bicarbonate is compromised, which leads to sustained alkalosis.

Endogenous causes5:02–5:34

Now for endogenous causes… Alright, if there are no exogenous causes of metabolic alkalosis, consider endogenous causes, and obtain a spot urine chloride test.
If the urine chloride is 20 milliequivalents per liter or less, it means there is significant renal chloride reabsorption so your patient has chloride-responsive metabolic alkalosis.
This is often found in conditions such as gastric alkalosis, cystic fibrosis, and laxative abuse. Let’s go over chloride-responsive metabolic alkalosis.

Chloride-responsive metabolic alkalosis5:34–7:54

Let’s start with gastric alkalosis also known as contraction alkalosis. During vomiting or nasogastric suction, hydrogen chloride is lost in the form of gastric acid, so less acid reaches the duodenum where hydrogen chloride is necessary to counterbalance the pancreatic and duodenal secretions of bicarbonates.
With insufficient acid, an excess of bicarbonate gets absorbed into the bloodstream, contributing to metabolic alkalosis.
Patients with gastric alkalosis typically present with a history of vomiting or prolonged nasogastric suction. The physical exam might reveal signs of hypovolemia, such as increased heart rate, decreased blood pressure, and dry mucous membranes.
With these findings, diagnose gastric alkalosis. Next up is cystic fibrosis, in which excessive amounts of sodium chloride and water are lost through sweat, leading to extracellular volume contraction.
This activates the renin-angiotensin-aldosterone system, or RAAS, which is followed by a rise in angiotensin II and aldosterone levels.
Increased aldosterone levels cause the kidneys to secrete more potassium and hydrogen ions while reabsorbing more bicarbonate, which eventually results in metabolic alkalosis.
The patient typically reports a history of recurrent respiratory infections, poor weight gain, and fatty stool, called steatorrhea.
The physical exam usually reveals digital clubbing, and lung crackles or wheezing. With these findings, consider cystic fibrosis.
Next, order a sweat chloride test and if it’s elevated, diagnose cystic fibrosis. Okay, time to talk about laxative abuse.
History might reveal the use of laxative medications and possibly an eating disorder like bulimia nervosa. Since some patients might not be comfortable reporting this in their history, during physical exam look for signs of self-induced vomiting, such as tooth decay and abrasions on the dorsum of the hands or fingers.
CMP usually reveals decreased serum potassium levels. If you see these findings, think laxative abuse.
Alright, let’s go back to the urine chloride and discuss situations where it exceeds 20 milliequivalents per liter. In this case, diagnose chloride-resistant metabolic alkalosis.

Chloride-resistant metabolic alkalosis7:54–8:14

Your next step is to assess the patient’s blood pressure to narrow down potential causes. If your patient is normotensive and has recently begun taking loop or thiazide diuretics their chloride-resistant metabolic alkalosis is due to acute diuretic use.

Normotensive8:14–11:23

Here are some high-yield facts! Laxative abuse causes a loss of potassium through the stool, which ultimately leads to hypokalemia.
At the cellular level, hypokalemia triggers an exit of potassium ions out of the cells, and an entry of hydrogen ions into the cells.
This reduces the overall hydrogen ion concentration relative to the bicarbonate level in the blood, eventually resulting in metabolic alkalosis.
However, if laxative abuse induces severe diarrhea over an extended period, there will be an excessive loss of bicarbonate ions as well, morphing into metabolic acidosis.
Now, loop and thiazide diuretics work similarly by increasing urine loss of potassium and hydrogen ions, relative to the serum bicarbonate level, resulting in metabolic alkalosis.
That’s why urinary potassium can help you differentiate between the two. If it’s less than 30 milliequivalents per day, you are dealing with hypokalemia or laxative abuse.
On the flip side, if it’s more than 30 milliequivalents per day in a patient without hypertension, that’s probably diuretic abuse, or Bartter or Gitelman syndrome.
And here’s a clinical pearl! Loop and thiazide diuretics cause chloride–resistant metabolic alkalosis only when they are taken acutely.
If either drug is taken chronically, the urine chloride will eventually drop between doses, resulting in chloride-responsive metabolic alkalosis.
Alright, let’s move on to Bartter and Gitelman syndromes, which are both autosomal recessive conditions associated with defective reabsorption of sodium ions, chloride ions, and water by the kidneys.
This leads to a decrease in the extracellular fluid volume, activating RAAS. The result will be the loss of potassium and hydrogen ions, and the reabsorption of more bicarbonate ions, ending up in metabolic alkalosis.
These patients present with polyuria and polydipsia, abdominal cramps, and possibly muscle weakness. There might be a personal or familial history of chronic diarrhea.
On CMP, there is decreased serum potassium. With these findings, consider genetic conditions like Bartter or Gitelman syndrome.
To distinguish between the two order genetic testing. If the results show SLC12A1 gene mutation, diagnose Bartter syndrome.
On the other hand, if genetic testing reveals SLC12A3 gene mutation, that’s Gitelman syndrome. Here’s a clinical pearl!
Children with Bartter syndrome typically have increased urinary calcium excretion with normal serum magnesium, while those with Gitelman syndrome usually have low urinary calcium excretion and low serum magnesium.
Now let’s shift our focus to hypertensive patients. Here, your next step is to check plasma renin activity.

Hypertensive11:23–11:31

If plasma renin activity is high, consider a renin-secreting tumor. To confirm, order an abdominal ultrasound or a CT.

High plasma renin activity11:31–12:51

If it shows a renal tumor, you have your diagnosis of a renin-secreting tumor. On the other hand, if there’s no renal tumor, consider renal artery stenosis.
In this condition, compromised blood flow to the kidneys can activate RAAS, causing the rise of angiotensin II and aldosterone levels.
Aldosterone stimulates the secretion of more potassium and hydrogen ions while enhancing the reabsorption of bicarbonate, which eventually leads to metabolic alkalosis.
To confirm the diagnosis, order a color Doppler ultrasound. If it detects turbulent blood flow in the renal artery, diagnose renal artery stenosis.
Now, if plasma renin activity is low, you should check your patient’s plasma aldosterone level. If it is also low, consider Cushing syndrome as your diagnosis.
To confirm, get a late-night salivary cortisol, a 24-hour urinary-free cortisol level, or a low-dose overnight dexamethasone suppression test.
The cortisol level above the reference range confirms the diagnosis of Cushing syndrome. Here’s a high-yield fact!
In Cushing syndrome, the excess cortisol can mimic the effect of aldosterone by binding to the kidney’s mineralocorticoid receptors.
This will result in hypokalemia, which eventually leads to metabolic alkalosis. Finally, if the plasma aldosterone level is high, consider hyperaldosteronism as the cause of metabolic alkalosis.

Low plasma renin activity12:51–13:30

Next, obtain an abdominal CT scan, and if it shows an adrenal mass, diagnose primary hyperaldosteronism as the cause of metabolic alkalosis.
Alright, as a quick recap… Metabolic alkalosis refers to an increase in serum bicarbonate concentration, either due to the loss of hydrogen ions from the body or the gain of bicarbonate itself.
The diagnosis is confirmed when the arterial pH exceeds 7.45, and bicarbonates are above 27 milliequivalents per liter. Causes of metabolic alkalosis can be exogenous or endogenous, which can be further divided into chloride-responsive and chloride-resistant metabolic alkalosis.

Review13:30–13:57

diagnosis is confirmed when the arterial ph exceeds 7.45 and bicarbonates are above 27 milliequivalents per liter Causes of metabolic alkalosis can be exogenous or endogenous which can be further