Approach to metabolic acidosis: Clinical sciences

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Introduction 0:00–0:51

Metabolic acidosis refers to an increase in hydrogen ion concentration and a decrease in bicarbonate concentration in the blood.
This can cause the pH to fall below 7.35 and serum bicarbonate level under 22 milliequivalents per liter. As a reference bicarbonates normally range from 22 to 27 miliequivalents per liter.
Metabolic acidosis can be classified as either normal anion gap metabolic acidosis, which occurs in conditions like renal tubular acidosis, or elevated anion gap metabolic acidosis, which is seen in conditions like ketoacidosis.
If a patient presents with a chief concern suggesting metabolic acidosis, first perform an ABCDE assessment to determine if they are unstable.

Unstable Patient 0:51–1:32

If your patient is unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access, put your patient on continuous vital sign monitoring, and provide supplemental oxygen, if needed.
Here’s a clinical pearl! Severe cases might present with nausea, vomiting, lethargy, and tachypnea; and might need treatment with hemodialysis.
Let’s move on to stable patients. First, obtain a focused history and physical exam and order labs, including an arterial blood gas analysis or ABG, and CMP.

Stable Patient 1:32–3:26

Patients may report diarrhea and vomiting, or they may have a history of diabetes mellitus. The physical exam might reveal signs of dehydration, such as dry oral mucous membranes and decreased skin turgor, and there might be an increased respiratory rate as the body tries to compensate for the acidosis.
If the ABG shows an arterial pH below 7.35 and the CMP shows decreased serum bicarbonate, typically below 22 milliequivalents per liter, that’s metabolic acidosis.
Here’s a clinical pearl! In metabolic acidosis, the body tries to compensate by increasing the rate and depth of breathing, which eliminates CO2 and lowers the pCO2.
To assess if the compensation is adequate, use the Winter formula: the range of expected pCO2 is equal to 1.5 times the bicarbonate level, plus 8, and plus or minus 2.
If the measured pCO2 falls within this calculated range, the respiratory compensation is adequate. On the flip side, if the measured pCO2 is higher than calculated, there might be both metabolic and respiratory acidosis occurring at the same time.
Lastly, if the measured pCO2 is lower than calculated, your patient might be having concurrent metabolic acidosis and respiratory alkalosis.
Now that you know your patient has metabolic acidosis, your next step is to calculate the anion gap. The normal anion gap is due to the difference between unmeasured anions like sulfate, phosphate, albumin, and organic anions and cations such as potassium, magnesium, and calcium.

Assess anion gap 3:26–5:04

Therefore, fluctuations in these unmeasured anions and cations may influence the anion gap. To calculate use this formula: serum sodium minus the sum of the serum chloride and bicarbonate.
Okay, let’s go over a normal anion gap range. A normal anion gap ranges from 4 to 12 milliequivalents per liter.
If your patient has a normal anion gap, look for the specific cause. To remember the causes of normal anion gap metabolic acidosis, use the mnemonic HARDUPS.
H stands for hyperalimentation, which is the delivery of nutrients into the vein, hypoadrenalism and hypoaldosteronism; A for acetazolamide, R for renal tubular acidosis, D for diarrhea, U for ureterostomies, P for post-hypocapnic state, and finally, S stands for spironolactone as well as saline infusion.Okay, let’s first go over iatrogenic causes, referring to hyperalimentation, saline infusion, and acetazolamide.

Normal anion gap metabolic acidosis 5:04–7:34

In such cases, patients might have a recent history of receiving total parenteral nutrition or TPN, or infusion of a large volume of IV normal saline When amino acids in TPN are metabolized, a lot of hydrogen ions are released which decreases the pH.
Next, saline in large amounts can dilute the serum bicarbonate concentration and disrupt the body's acid-base balance due to excess chloride administered relative to sodium.
Additionally, they might report taking medications, such as carbonic anhydrase inhibitors, like acetazolamide, or potassium-sparing diuretics, like amiloride.
If this is the case, your patient’s metabolic acidosis is due to iatrogenic causes. Moving on to renal tubular acidosis, which causes metabolic acidosis due to either impairment of hydrogen secretion like in types 1 and 4 or bicarbonate absorption like in type 2.
These patients often report muscle weakness, and possibly a history of recurrent urinary tract infections and kidney stones.
Their CMP may show slightly elevated BUN and creatinine. With these findings, consider renal tubular acidosis, and calculate the eGFR.
Normal eGFR, meaning above 60 milliliters per minute, confirms your diagnosis of renal tubular acidosis. Next up is gastrointestinal loss of bicarbonate through diarrhea.
Patients typically report profuse diarrhea, while the physical exam may show signs of dehydration, like dry mucous membranes or decreased skin turgor.
Additionally, CMP reveals decreased sodium and potassium levels. If you see these findings, the patient’s metabolic acidosis is due to gastrointestinal loss of bicarbonate.
Let's go over an elevated anion gap range. Let’s start with methanol and ethylene glycol toxicity.

Elevated anion gap metabolic acidosis 7:34–15:33

Alright, let’s take a step back to the anion gap, and have a look at individuals with an anion gap of more than 12 milliequivalents per liter.
In this case, your patient has an elevated anion gap metabolic acidosis. To remember the causes, use a mnemonic GOLD MARK.
G stands for glycols, O for oxoproline, L for L-lactate, D for D-lactate, M for methanol, A for aspirin, R for renal failure, and lastly, K stands for ketoacidosis.
These patients typically present with a history of ingestion of toxic alcohol from household agents like antifreeze or windshield washer fluid.
Additionally, they might have a new-onset blindness usually with methanol toxicity, and the physical exam may show altered mental status.
With these findings, consider either methanol or ethylene glycol toxicity. To confirm, obtain serum methanol and ethylene glycol levels.
If the methanol level is elevated, diagnose methanol toxicity. However, if the ethylene glycol level is elevated, diagnose ethylene glycol toxicity.
Here is a high-yield fact! Methanol toxicity triggers metabolic acidosis through its conversion into formic acid, which in turn inhibits mitochondrial function, resulting in the accumulation of lactic acid.
An almost similar process occurs with ethylene glycol toxicity. Once converted into its metabolites, glycolic acid and oxalic acid, it causes depression of the central nervous system and renal failure, ultimately resulting in metabolic acidosis.
Next up is lactic acidosis. These patients typically have a history of recent shock.
The physical exam might reveal signs of poor tissue perfusion, such as low blood pressure, increased heart rate, cool extremities, and prolonged capillary refill time.
With these findings, consider lactic acidosis. To confirm, order a serum lactic acid, and if it is elevated, you can diagnose lactic acidosis.
Now, isoniazid overdose can inhibit the conversion of lactate to pyruvate in the liver, resulting in lactate accumulation.
Patients often present with acute onset of nausea and vomiting and a history of tuberculosis treated with isoniazid. The physical exam may show altered mental status.
If you see this, think isoniazid toxicity. Another cause of lactate accumulation is iron toxicity, which can cause mitochondrial dysfunction by interfering with the Krebs cycle, ending up with cellular death and lactate accumulation.
These patients typically report excessive iron ingestion, usually in the form of supplements, and may have abdominal pain, vomiting, and fever.
In severe cases, there might be hematemesis or hematochezia. The physical exam reveals an elevated body temperature and low blood pressure.
With these findings, consider iron toxicity. To confirm, order serum iron level.
If it’s elevated, diagnose iron toxicity. Here’s a high-yield fact!
Short bowel syndrome can also cause an accumulation of lactate. Because sugars don’t get fully absorbed, gut bacteria convert them to D-lactate, which can accumulate, leading to acidosis.
Next up is salicylate toxicity. Patients typically report ingestion of salicylate-containing medications, such as aspirin.
The physical exam reveals an increased respiratory rate and depth of breathing and low blood pressure. With these findings, consider salicylate toxicity and order serum salicylate level.
If it comes back elevated, that’s salicylate toxicity. Here’s another high-yield fact!
Salicylate toxicity can cause both respiratory alkalosis and metabolic acidosis. Salicylates directly stimulate the medulla, which causes hyperventilation and subsequent respiratory alkalosis.
As salicylates get metabolized, keto acids and lactic acid build up, leading to metabolic acidosis. When these mechanisms are combined, they can result in a normal arterial pH.
Okay, let’s consider severe renal disease. These patients typically report decreased urine output, nausea, vomiting, and fatigue.
They might also have a known history of kidney disease. The physical exam might reveal elevated blood pressure and peripheral edema.
Next, CMP typically reveals elevated BUN, creatinine, and potassium. With these findings, consider renal disease.
To confirm, calculate the eGFR. If it is under 30 milliliters per minute, you can diagnose severe renal disease.
Here is a clinical pearl! When the eGFR is 30 to 59 milliliters per minute, your patient has moderate renal disease.
Unlike severe renal disease, where the kidneys are unable to excrete excessive acid build-up, in moderate renal disease, there is usually adequate acid excretion so the anion gap is maintained within the normal range.
Time to move on to ketoacidosis. Patients often report unintentional weight loss, abdominal pain, and vomiting.
They may also have a history of diabetes mellitus with poor insulin adherence, prolonged fasting, or excessive alcohol use.
The physical exam may reveal signs of dehydration including dry mucous membranes and decreased skin turgor. There might also be a fruity odor to the breath.
Finally, look out for Kussmaul breathing, which is a rapid and deep pattern of breathing, reflecting the body’s attempt to compensate for the low arterial pH by expelling excess CO2.
With these findings, consider ketoacidosis. To confirm, order labs, including serum ketones and a urinalysis.
If serum ketones are elevated, and urinalysis reveals ketonuria, you can diagnose ketoacidosis. Alright, as a quick recap...

Review 15:33–16:15

Metabolic acidosis refers to increased hydrogen ion concentration with decreased bicarbonate concentration in the blood.
The diagnosis is confirmed when the arterial pH is below 7.35, and the bicarbonate level is less than 22 milliequivalents per liter.
Causes of normal anion gap metabolic acidosis can be remembered with a mnemonic HARDUPS, while GOLD MARK is a good mnemonic to remember the causes of elevated anion gap metabolic