Acid-Base – Nephrology Topic 1

Acid-Base disorders require understanding of the underlying pathophysiology as well as familiarity with some formulas. Several Acid-Base scenarios that can be tested on USMLE Step 3 are
A) Identifying the acid base disorder
B) Identifying the etiology of acid-base imbalance in an Multiple choice question by elimination process of other choices based on the acid-base characterestic.
C) Diagnosing mixed acid-base disorders by applying simple formulas
D) Causes and treatment of increased anion gap acidosis
E) Causes of Non-Gap Acidosis
F) Renal tubular acidosis and identifying the etiology of the RTA from subtle clues in the question stem.
G) Osmolar gap and using this concept to identify the etiology in metabolic acidosis and in toxicology.

Memorize the following formulas:

1) Anion gap = (Na+)-{(Cl-)+(Hco3-)}
Normal gap is 4 to 12.

Anion gap greater than 12 indicates increased anion gap metabolic acidosis. This indicates the presence of a foreign substance causing acid-base imbalance.
If there is acidosis ( low bicarb <>It is important to know the distinction because the causes of increased gap metabolic acidosis are different from non-gap acidosis. So, once you know whether the gap is increased or not, you can further focus only on the relevant causes.

Causes of Increased Gap Acidosis ( MUDPILES)
– Methanol (M)
– Uremia (U)
– Diabetic Ketoacidosis ( D)
– Paraldehyde, Propylene glycol ( P)
– Isoniazid ( I)
– Lactic acid (L)
– Ethylene Glycol (E)
– Salicylic acid ( S)

Causes of Non-Gap acidosis : The gap here is normal because when the hco3- drops, there is a compensatory increase in the chloride there by, keeping the gap normal. This indicates no foreign substance but it is because of the loss of bicarbonate either through the GI tract ( Diarrhea) or Renal system ( RTA). These causes are:

– Gastrointestinal loss of Bicarbonate : Diarrhea, small bowel fistulas, urinary diversion
– Renal causes : Renal tubular acidosis, renal insufficiency, hypoladosteronism.
– Recovery phase of DKA

Concept of Urine Anion Gap
Now, let us say you have a metabolic acidosis and the gap is normal –> you know that this is normal anion gap acidosis. But there are two important causes of normal gap acidosis as you have already seen earlier – GI vs. Renal . How do you differentiate between the two?
For this, you will need to know URINE ANION GAP

Urine Anion Gap (UAG) = {(urineNa)+(urineK+)}-(urine Cl-)
Normal values for UAG is -10 to +10.
A logical approach here is to look at the urine Na+. If urine Na+ is low ( which you would expect in dehydration, diarrhea etc), urine anion gap tends to be more negative and points towards GI losses ( such as diarrhea)
So, a UAG < -10 ( more negative gap) indicates a GI cause for Non Gap Acidosis where as a UAG > +10 indicates a Renal Tubular Acidosis.
If you have difficulty remembering this, remember neGUTive – negative UAG in bowel (GUT) causes.

Renal Tubular Acidosis ( RTA)
A normal gap metabolic acidosis with positive urine anion gap ( UAG) could be due to RTA. There are different types of RTA.
Type 1 ( distal)
Type 2 (proximal)
Type 4 (hyporeninemic hypoaldosteronism)

On the exam, once you identify a metabolic acidosis and then identify an RTA, you will be tested on the etiology of that RTA. So, it is important to know how to differentiate between different RTAs and their causes.

To differentiate between various RTAs, first look at the serum potassium. If K+ is high in an RTA , this is most likely Type 4 ( because low aldosterone causes decreased renal excretion of acid and potsssium) If the potassium is normal or low, then the RTA could be Type 1 (Distal) or Type II (Proximal). You will need to look at the urine pH to differentiate between Distal and Proximal RTA. Remember that Distal RTA can never acidify the urine so, the Urine pH is never less than 5.5. So, if a MCQ gives a urine pH of less than 5,5, you are most likely dealing with Proximal RTA.

Type 1 RTA – Distal RTA :
– Causes: autoimmune diseases ( scleroderma), hyperglobinemia states and hereditary
– Present with normal anion gap acidosis, urine pH >5.5, hypokalemia, hypercalciuria, nephrocalcinosis and stones
– Treatment: alkali i.e. K citrate

Type II RTA – Proximal RTA :
– Failure to reabsorb filtered bicarbonate in the proximal tubule
– Presents with Hypokalemia and normal gap acidosis
– Urine pH > 5.5, but it will be less than 5.5 once serum HCO3 is less than 16
– Causes: Multiple myeloma, Acetozolamide, Ifosfamide Lead, cadmium, copper

Type IV RTA – Hyporeninemic Hypoaldosteronism
Causes: diabetes mellitus, HIV and tubulo-interstitial disease
– Present with hyperkalemia, normal anion gap acidosis and normal urine pH

Identifying Mixed Acid-Base Disorder in Metabolic acidosis

To understand if a patient has both increased anion gap acidosis and non-gap acidosis at the same time or metabolic acidosis + metabolic alkalosis at the same time, you will need to know the concept of “Delta Gap” . Delta gap is logically explained in the video clip below. Logically, if the serum bicarbonate (Hco3-) falls more than the change in the anion gap, then a patient has both non-gap+increased gap acidosis. If the serum bicarbonate falls less than the change in the anion gap, then the patient has mixed disorder – metabolic acidosis + metabolic alkalosis.

For example, if the anion gap is 20 –> you can say the change in the anion gap is 8 ( because normal anion gap is 12. ) In this scenario let us say if the MCQ gave serum hco3- as 10, drop in the serum bicarb here is 14 ( remember, for calculation normal serum bicarb is taken as 24. so, if it is 10 now, the drop in bicarb is obviously, 14). –> this means when your anion gap has increased by 8 your bicarb has fallen more than 8 i.e; by 14….that means some other factor apart from the factor responsible for increased gap acidosis is also contributing to acidosis here! – this suggests co-existing increased anion-gap+normal-gap acidosis . A classic example is diarrhea with shock – where diarrhea causes non gap acidosis but shock can lead to lactic acidosis which increases the gap – so, things can co-exist!

B) To understand if your patient has a mixed disorder of metabolic acidosis + respiratory acidosis or metabolic acidosis + respiratory alkalosis, you will need to be familiar with Winter’s formula.

Winter;s formula :
Expected pCo2 = {1.5(Hco3-) +8} +/-2

If your patient has metabolic acidosis, you expect him to breathe fast and wash out the Co2 so as to maintain the pH in normal limits …this is called “Compensation”. Compensation brings the serum pH towards the normal but never makes it completely normal – so, if you are seeing a normal pH in a metabolic acidosis , you can right away say that you are dealing with a Mixed disorder rather than a compensation alone.

The expected Pco2 in the above formula is the one that is expected as a comprnsation if your patient has low bicarbonate or metabolic acidosis. You need to compare this expected Pco2 with the real value of Pco2 obtained on the arterial blood gases ( measured Pco2).

Pearls for answering questions on Mixed Disorders:

A) If measured Pco2 is lower than the expected Pco2, that means your patient is washing out more C02 than expected —meaning, he has respiratory alkalosis co-existent with metabolic acidosis ( one example of such mixed disorder is Salicylate toxicity) .

B) If measured Pco2 is higher than expected Pco2, that means your patient is retaining Co2 which means he has a co-existent Respiratory acidosis along with metabolic acidosis ( eg: Cardiac arrest can cause such mixed acidosis because reduced respiratory drive causes CO2 retention leading to respiratory acidosis where as shock because of cardiac arrest causes lactic acidosis which is metabolic acidosis).

eg: If Hc03 – is 16, the expected PCo2 as per Winter;s formula should range between 30 to 34 ( see the above formula). However, let us say your patients Pco2 on the arterial blood gas is 20 –> you can call this metabolic acidosis + respiratory alkalosis. eg : Salicylate Toxicity

If Hc03 – is 16, the expected PCo2 as per Winter;s formula should range between 30 to 34 ( see the above formula). However, let us say your patients Pco2 on the arterial blood gas is 44 –> you can call this metabolic acidosis + respiratory acidosis. eg : Cardiac arrest

In this 35 minute clip, our instructing physician explains Hypercalcemia and Acid-Base disorders in simple terms. After listening to the clip, try to answer the self – assessment questions below.

Click Here

When the page opens, right click on the clip and “Zoom” to view full screen so as to have better audio/ video quality. These are on the web page itself so you may hear slight resound in the background unlike pay-per-view system which comes as a streaming video.

Self-Assessment Questions ( Copy right: USMLEGalaxy)
– will be posted soon!

9 Responses

  1. wonderful and simple explation and made easy thanks

  2. Very thorough and simple explanation for one of the most confusing concepts in Clinical Medicine.

  3. excellent work ! very well done.

  4. very nice & simplified lecture….

  5. Ah! I take a teensy coffee break from the blogging realm and come
    back to find that you have become amazing?!
    Wow, times have changed! Keep up the sensational

  6. I learned fist time so easily about RTA , thanks for the nice explaination

  7. Simple and easy to remember

  8. Mixed Disorders: I got confused instead. I am revising after a while so might be missing out on something. But please tell me how can we say HCO3- is not meeting the Anion Gap when we actually calculate the gap Using HCO3- !?

    Albumin’s role in unmeasured anions also didn’t make sense to me (blaming my understanding to be honest)

  9. Never mind 🙂 did some research and found this;
    – : Check a Delta Gap,
    If the Anion Gap is greater than 20mEq/L, then a Delta Gap needs to be calculated to determine if additional metabolic disorders are present.
    Delta Gap = Anion Gap – 12
    If Delta Gap + HCO3 > 30, the patient also has Metabolic Alkalosis present
    If Delta Gap + HCO3 < 23, the patient also has NAGMA present

    – The normal "Gap" in the Anion Gap Equation is because of Albumin etc. Albumin increase/decrease needs for the Gap to be readjusted to interpret accordingly.

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