The Curbsiders podcast

#88: Acid base, boy bands, and grandfather clocks with Joel Topf MD

March 26, 2018 | By

Dominate acid-base disturbances with the wisdom of @kidney_boy aka Joel Topf, MD, Chief of Nephrology at Kashlak Memorial Hospital.  Master the 5 steps for interpreting acid-base disorders and decode any ABG, VBG, and BMP to find the primary disorder, and any other disorders “tucked away in the ABG”! Plus: Henderson-Hasselbalch and pH simplified; the anion gap, should your correct it?; choice of IV fluid; osmolar gaps, methanol, ethylene glycol, isopropyl alcohol; and how metabolic disorders are like a boy band. Be sure to follow along the Dr. Topf’s [brilliant acid-base PowerPoint]. Test Yo Self. Take our quiz here!

Written and produced by Joel Topf MD, Shreya Trivedi MD, Xavi Jimenez MD; Images by Hannah Abrams; Slides by Joel Topf MD; Edited by Matthew Watto MD

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Acid Base PowerPoint compliments of Joel Topf, MD aka @kidney_boy

Clinical Pearls:

  1. Value of the arterial blood gas (ABG): It must be interpreted based on the underlying disease (e.g. pH 6.8 from seizure is no big deal, but pH of 6.8 from methanol toxicity means death).
  2. Alkalosis is better tolerated than acidosis because the relative change in hydrogen ion concentration [H+] is smaller. [H+] doubles as pH increases or decreases by 0.3 (e.g. If pH goes from 7.4 to 7.1 (acidosis) then [H+] increases by 40 from [40 nmol/L] to [80 nmol/L]. If pH goes from 7.4 to 7.7 (alkalosis) then [H+] decreases by 20 from [40 nmol/L] to [20 nmol/L].
  3. Acidemia means pH is below 7.4 versus acidosis, which is any process that tends to lower the pH. Alkalemia means pH is above 7.4 and alkalosis is any process that raises the pH.
  4. Compensation is always in the same direction of the primary disorder and brings the pH towards normal.
  5. In Metabolic disorders the pH, pCO2, and HCO3 all change in “One Direction”
  6. In Respiratory disorders the pH changes in the opposite direction of pCO2 and HCO3.
  7. Determining if a respiratory disorder is acute or chronic depends on a patient’s history and exam, NOT on which equation for compensation fits best.
  8. Anion gap (AG): Dr Topf corrects the AG like so: (4 – albumin) + AG = Corrected AG The total number of anions must equal the total number of cations (see gamblegram). In AG metabolic acidosis (AGMA) the HCO3 compartment get smaller. In non-AG metabolic acidosis (NAGMA) the chloride compartment gets larger. Anion gap is largely created by albumin and phosphorus so low albumin or phos can falsely lower the gap.
  9. Methanol and ethylene glycol ingestions are highly toxic causing AGMA, inebriation, coma, tachypnea/hyperpnea, hypotension, ocular toxicity (methanol), and renal failure (ethylene glycol). Use ethanol or fomepizole to block conversion to their toxic metabolites.
  10. When to give bicarbonate: Reasonable to give sodium bicarbonate to patients with renal tubular acidosis, or ongoing losses from diarrhea, or a surgical drain.

In-Depth Show Notes

Why do we care about the pH?
The hydrogen ion concentration can substantially affect protein structure and enzyme function. For every change in 0.3 pH units, [H+] changes by a factor of two. It is key to evaluate the cause of the acid-base disturbance.

Step 1: Determine the primary disorder

Acidosis or alkalosis?

  1. If the pH is less than 7.4, it is acidosis
  2. If the pH is greater than 7.4, it is alkalosis

Determine if its primary metabolic or respiratory.

  1. Compensation for the primary disorder will always be in the same direction as the primary disorder.
  2. If all three variables (pH, HCO2, pCO2) move in the SAME direction: it is a primary metabolic. “How is metabolic acidosis like a boy band? Everything moves in one direction!” –Joel Topf MD
  3. If all three variables (pH, HCO2, pCO2) move in the discordant direction: it is a primary respiratory.

Step 2: Is the compensation correct for the severity of the primary disorder?
The magnitude of the compensation is determined solely by the magnitude of the primary disorder

Metabolic disorders
Metabolic acidosis: the expected pCO2 can be estimated from the HCO3. Winter’s formula = Expected pCO2 = (1.5 x HCO3) + 8 ± 2

  1. If the pCO2 is higher than the predicted, then there is an additional respiratory acidosis
  2. If the pCO2 is lower than the predicted, then there is an additional respiratory alkalosis

Metabolic Alkalosis: PCO2 should rise 2/3 the increase in HCO3

Respiratory disorders
In respiratory disorders, the metabolic compensation is slow, thus the predicted bicarbonate needs to be calculated as pre-compensation, which is “acute” and after compensation, called “chronic”. Metabolic compensation is slow is because the kidneys excrete less than 0.1 mole of acid per day as NH3, phosphate and free hydrogen ions; in contrast, the lungs ventilate 12 moles of acid per day as Co2

Respiratory acidosis: In acute respiratory acidosis, for every 10 mmHg increase in pCO2, the HCO3 should increase 1 mEq/L vs. 3 mEq/L in chronic compensation

Respiratory alkalosis: In acute respiratory alkalosis, for every 10 mmHg decrease in pCO2, the HCO3 should decrease 2 mEq/L  vs. 4 mEq/L in chronic compensation

Step 3: If there is a metabolic acidosis, is there an anion gap?

Anion gap = Na – (HCO3 + Cl)

Another way to think of “Is there an anion gap?” is asking if the anion associated with the increased H+ cation is chloride (non-anion gap metabolic acidosis) or not chloride (anion gap metabolic acidosis)

Hypoalbuminemia and hypophosphatemia can mask an anion gap (particularly, low albumin states usually underestimate the anion gap). To estimate the normal anion gap for that patient, either:

  1. Multiply the albumin by 2.5 and add half the phosphorous OR
  2. For every g/dL the albumin is below 4, add 2.5 to the calculated anion gap

GOLDMARK is new anion gap mnemonic for the 21st century. This acronym represents Glycols (ethylene and propylene), Oxoproline, L-lactate, D-lactate, Methanol, Aspirin, Renal failure, and Ketoacidosis

Three “new” organic anion-gap-generating acids and acid precursors have been recognised in recent years (An Mehta)

  1. D-lactic acid, which can occur in some patients with short bowel syndromes
  2. 5-oxoproline (or pyroglutamic acid) associated with chronic paracetamol use (aka acetaminophen), often by malnourished women.
  3. High doses of propylene glycol (solvent used for several parenteral medications) from continuous infusions, including: lorazepam, phenobarbital.

Step 4: If there is an anion gap metabolic acidosis (AGMA), is there an osmolar gap?

  1. In the presence of a large anion gap (>20-25) of undetermined etiology calculate the osmolar gap to help rule out the presence of a toxic alcohol e.g. methanol or ethylene glycol.
  2. Osmolar gap = difference between the measured osmolality (which includes the toxic alcohol) and the calculated osmolality (does not include the toxic alcohol)

Calculated osmolality = (2x Na) + BUN/2.8 + Glucose/18 + Ethanol/3.7

  1. Osmolar gap present if measured osmolality is significantly more (usually >10) than the calculated osmolality.
  2. The osmolar gap is not specific. It may indicate: toxic alcohol poisoning, lactic acidosis, ketoacidosis, chronic kidney disease, and sickle cell syndrome may increase this gap (Kraut).
  3. A normal osmolal gap cannot be used to rule out toxic alcohol ingestion since some patients with toxic alcohol poisonings can have osmolal gaps within the normal range (Krasowski).
  4. The osmolar gap also varies during the course of the intoxication (Ku). As the toxic alcohol accumulates, the osmolar gap elevates. Then, as its metabolism progresses that osmolar gap falls (Kraut). Thus, there should be a lot of caution when interpreting these results.

Step 5: If there is an anion gap metabolic acidosis, determine “the bicarbonate before”

This allows you to find yet another acid base disorder “tucked away in the ABG”. If there is an AGMA, then the anion gap should increase as the bicarbonate falls in a 1:1 fashion (loss bicarbonate = addition of anion). Use the following equation to assess for “the bicarbonate before” the anion gap acidosis was present : HCO3 + (AG – 12) = HCO3 before

  1. If the HCO3 before is less than 24, then there is a concomitant non-anion gap metabolic acidosis
  2. If the HCO3 before is greater than 24, then there is a pre-existing metabolic alkalosis
  3. If the HCO3 before is equal to 24 ± 2, then there is no pre-existing acid-base disorder

Toxic alcohols

  1. Methanol, ethylene glycol have a low molecular weight. Just a few ounces have a ton of osmoles and raise the plasma osmolality causing osmolar gap. Ingestions are highly toxic causing AGMA, inebriation, coma, tachypnea/hyperpnea, hypotension, ocular toxicity (methanol), and renal failure (ethylene glycol). An alcohol level above 100 mg/dL or fomepizole competitively inhibit alcohol dehydrogenase from converting methanol to formaldehyde and ethylene glycol to oxalic acid.
  2. Isopropyl alcohol can cause inebriation, coma, hypotension, and elevated osmolar gap, but does not cause AGMA.

If you plan to infuse sodium bicarbonate, what solution should you mix it with?
Avoid mixing sodium bicarbonate with normal saline solution since this solution will be  hypertonic.

  1. Example:  Each ampule of bicarbonate 8.4% has approximately 50 meq of sodium. Most bicarbonate drips consist of 3 ampules of sodium bicarbonate for a total of 150 meq of sodium. If you add this to 1 Liter of normal saline which usually has 154 meq of sodium, you will end up with approx 304 meq of sodium in your drip (osmolality = sodium x2 = 304 meq x2= 608 meq. Yikes!!!).
  2. If you plan to administer sodium bicarbonate, prepare your infusion by mixing 150 meq of sodium bicarbonate in D5W or 75 meq with ½ normal saline, NOT with normal saline!

Goal: Listeners will master the five steps to evaluate acid base disorders and explain the basic underlying chemistry and physiology at play.

Learning objectives:
After listening to this episode listeners will…

  1. Define pH and why hydrogen ion concentration matters
  2. Explain how the Henderson-Hasselbalch equation establishes a mathematical relationship between pH, pCO2 and HCO3
  3. Dispel myth that since the serum bicarb on the ABG is “calculated” it is less accurate than the measured one on a basic metabolic panel
  4. Recall the four primary acid base disorders
  5. Recall that compensation is the body just trying to get the pH back to normal, trying to normalize the ratio of HCO3:pCO2
  6. Remember that the ABG is a diagnostic and not a therapeutic tool with limited data showing that the correction of these variables actually helps patients.
  7. Diagnose and treat anion gap metabolic acidosis
  8. Explain why MUDPILES sucks. Explain GOLDMARK
  9. Explain how to evaluate for toxic alcohols using the osmolar gap
  10. Analyze how to assess for a concomitant metabolic disorder in anion gap metabolic acidosis  

Disclosures: Dr Topf and The Curbsiders report no relevant financial disclosures.

Time Stamps

  • 00:00 Announcement
  • 01:00 Disclaimer
  • 01:34 Intro
  • 02:45 The setup and guest bio
  • 03:15 How does Dr Topf compensate for difficulty
  • 07:10 What has helped Dr Topf become successful as an educator
  • 10:40 With which electrolyte do you most closely identify?
  • 14:05 Picks of the week
  • 16:05 Nephmadness explained
  • 19:50 Joel’s big picture look at acid base
  • 22:17 Acid base and logorhythmic scale
  • 24:28 A caution about ABGs
  • 27:23 Clinical case from Kashlak Memorial Hospital
  • 28:05 Misinterpretation of low bicarb on a metabolic panel
  • 29:20 Step 1 of acid base
  • 32:00 Metabolic disorders and One Direction
  • 35:15 Acidemia vs acidosis; alkalemia vs alkalosis
  • 37:52 Compensation for acid base disorders
  • 40:45 ABG apps and analyzers
  • 42:40 Step 2 Is there a second primary disorder? Use equations for determining if compensation is appropriate.
  • 51:31 How to determine if respiratory compensation is acute or chronic
  • 54:26 Step 3 The anion gap
  • 57:21 Correcting the anion gap
  • 60:33 What causes a low anion gap?
  • 63:58 Anion gap acidosis
  • 66:05 GOLDMARK
  • 69:15 Step 4 Is there an osmolar gap?
  • 71:48 Toxic ingestions: Methanol, ethylene glycol, and isopropyl alcohol
  • 76:15 Calculating the osmolar gap
  • 79:08 Step 5 Gap-gap calculation aka “the bicarbonate before”
  • 85:05 Choice of IV crystalloid fluid and when to use a bicarbonate drip
  • 88:15 Bicarbonate in DKA
  • 90:18 NephMadness plug
  • 91:10 Outro

Links from the show:

  1. TED Talk by Adam Grant on originals and procrastination
  2. Originals (book) by Adam Grant
  3. Moon (film) by Duncan Jones
  4. #Womeninmedicine Chat Sunday nights 9pm on Twitter
  5. Fill out your bracket for Nephmadness
  6. MedCalX Medical Calculator w/ABG analyzer
  7. GOLD MARK: an anion gap mnemonic for the 21st century. AN Mehta, JB Emmett , M Emmett, Lancet,   372, 9642, p 892, 2008
  8. Precious Bodily Fluids Blogpost on alternate names prior to GOLDMARK
  9. Krasowski MD, Wilcoxon RM, Miron J. A retrospective analysis of glycol and toxic alcohol ingestion: utility of anion and osmolal gaps. BMC Clin Pathol 2012; 12: 1.
  10. Ku E, Cheung EL, Khan A, Yu ASL. Anion and osmolal gaps after alcohol intoxication. Am J Kidney Dis 2009; 54: 385-8.
  11. Kraut JA, Mullins, ME. Toxic Alcohols. N Engl J Med 2018; 378:270-28
  12. Gomez, Hernando, and John A. Kellum. “Understanding acid base disorders.” Critical care clinics 31.4 (2015): 849-860.


  1. March 29, 2018, 2:15pm Tom Cornish writes:

    Fantastic episode, following along with the powerpoint until the equations, and unfortunately the units in the UK are different to here. I may try again at some point, but trying to convert to UK units whilst thinking about the cases was a bit too fast for me!

  2. March 31, 2018, 5:40pm Araceli Leon writes:

    This is by far one of the most helpful episodes I have listened to! I'm a 4th year pharmacy student and will be doing a critical care rotation in April, so this episode comes at a perfect time for me. Also, I really enjoy the 15 minutes you take to talk more about yourselves, the host, and just life! Students often forget about self-care and your 15-minute intro is a healthy reminder that there is more to life than being consumed by a career in health care. Love you all!

  3. April 16, 2018, 6:41pm Thomas writes:

    Great episode. I always enjoy hearing you talk with Dr. Topf. I won‘t mind more episodes with him. „Dr Topf corrects the AG like so: (4 – albumin) + AG = Corrected AG“ I thought it is (4 — albumin) x 2.5 + AG = Corrected AG ??? Our mnemonic in Germany is KUSSMAUL: Ketons Uraemia Salicylate (Salicylate) Methanol Äthylenglykol (=Ethylene glycol) (Uraemia) Lactate The GOLDMARK one is great though. By the way „Topf“ is German an means pot/jar ;—)

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