Step-by-step flowchart: Acid-base physiology

Acid–base questions love to look scary, but they’re usually a repeatable pattern-recognition game: identify the primary disorder, check compensation, then decide if there’s a mixed problem—and only then hunt the cause. Here’s a step-by-step flowchart you can run in under a minute on USMLE.

The 60-second acid–base flowchart (renal-focused)

Step 1) Look at the pH

pH < 7.35 → acidemia
pH > 7.45 → alkalemia

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One-liner: The pH tells you the direction; the next steps tell you the driver.

Step 2) Identify the primary process (HCO₃⁻ vs PaCO₂)

Use the rule:

HCO₃⁻ moves pH in the same direction
- ↓HCO₃⁻ → metabolic acidosis
- ↑HCO₃⁻ → metabolic alkalosis
PaCO₂ moves pH in the opposite direction
- ↑PaCO₂ → respiratory acidosis
- ↓PaCO₂ → respiratory alkalosis

Quick mnemonic:
“ROME”

Respiratory Opposite (PaCO₂ opposite pH)
Metabolic Equal (HCO₃⁻ equals pH direction)

Step 3) Check if compensation is appropriate (to catch mixed disorders)

If primary metabolic acidosis → use Winter’s formula

$\text{Expected PaCO}_2 = 1.5(\text{HCO}_3^-) + 8 \pm 2$

Measured PaCO₂ higher than expected → additional respiratory acidosis
Measured PaCO₂ lower than expected → additional respiratory alkalosis

If primary metabolic alkalosis → expected respiratory compensation

Rule of thumb:

PaCO₂ rises about 0.7 mmHg per 1 mEq/L rise in HCO₃⁻
(Or memorize: “met alkalosis → hypoventilate, but not perfectly”)

If primary respiratory disorder → kidneys compensate (this is the renal gold)

Use these high-yield deltas:

Primary disorder	Acute compensation (HCO₃⁻ change)	Chronic compensation (HCO₃⁻ change)
Respiratory acidosis (↑PaCO₂)	+1 mEq/L per +10 PaCO₂	+3–4 mEq/L per +10 PaCO₂
Respiratory alkalosis (↓PaCO₂)	−2 mEq/L per −10 PaCO₂	−4–5 mEq/L per −10 PaCO₂

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One-liner: Acute = small renal change, chronic = big renal change (because kidneys need time to reprogram transporters and ammoniagenesis).

Step 4) If metabolic acidosis → calculate the anion gap (AG)

$\text{AG} = \text{Na}^+ - (\text{Cl}^- + \text{HCO}_3^-)$

“Normal” AG is roughly 8–12 (depends on lab)
Correct for albumin (super high-yield): $\text{Corrected AG} = \text{AG} + 2.5(4 - \text{albumin})$

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One-liner: Low albumin hides an anion gap acidosis unless you correct it.

Step 5) If AG metabolic acidosis → do the delta gap (mixed metabolic disorders)

$\Delta\text{AG} = \text{AG} - 12$
$\Delta\text{HCO}_3^- = 24 - \text{HCO}_3^-$

If $\Delta\text{AG} > \Delta\text{HCO}_3^-$ → concurrent metabolic alkalosis
If $\Delta\text{AG} < \Delta\text{HCO}_3^-$ → concurrent non–anion gap metabolic acidosis

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One-liner: The delta gap tells you if another metabolic process is “pulling” HCO₃⁻ beyond what the AG explains.

Visual: the “Acid–Base Ladder” (shareable mental image)

Picture a ladder with pH at the top, and two rungs underneath: PaCO₂ (lungs) and HCO₃⁻ (kidneys).

Top rung: pH says acidemia vs alkalemia
Middle rung: PaCO₂ points to respiratory driver
Bottom rung: HCO₃⁻ points to metabolic/renal driver
Side rails: compensation rules keep you from falling for a mixed disorder

One-liner: “pH chooses the lane, PaCO₂/HCO₃⁻ chooses the driver, compensation checks if someone else is in the car.”

Renal physiology that actually shows up in acid–base questions

How kidneys fix acid: “Reclaim bicarb + create new bicarb”

You have two jobs:

Reabsorb filtered HCO₃⁻ (mostly proximal tubule)
Generate new HCO₃⁻ by excreting acid (distal nephron)

Proximal tubule (bulk work)

Carbonic anhydrase enables:
Filtered HCO₃⁻ → CO₂ (diffuses in) → re-forms HCO₃⁻ inside cell → returned to blood
NHE3 (Na⁺/H⁺ exchanger) secretes H⁺ into lumen to allow HCO₃⁻ reclamation

High-yield tie-in: Acetazolamide (CA inhibitor) → proximal RTA (type 2)-like effect early: ↑HCO₃⁻ loss → metabolic acidosis, alkaline urine initially.

Alpha-intercalated cells (distal acid secretion)

Secrete H⁺ via H⁺-ATPase and H⁺/K⁺-ATPase
Generate new HCO₃⁻ returned to blood
Trap H⁺ as:
- H₂PO₄⁻ (titratable acid)
- NH₄⁺ (ammonium) from proximal glutamine metabolism

High-yield tie-in: Chronic acidosis → ↑ammoniagenesis → more NH₄⁺ excretion (major adaptive mechanism).

Beta-intercalated cells (base secretion)

Secrete HCO₃⁻ (pendrin, Cl⁻/HCO₃⁻ exchanger)
Used in alkalosis states

The “3 metabolic acidosis buckets” (with renal hooks)

1) Anion gap metabolic acidosis (AG ↑): “Add acid”

Classic mnemonic: GOLD MARK

Glycols (ethylene/propylene)
Oxoproline (chronic acetaminophen)
L-lactate
D-lactate
Methanol
Aspirin (late: AG metabolic acidosis; early: resp alkalosis)
Renal failure (uremia)
Ketoacidosis (DKA, alcoholic, starvation)

Renal pearl: Uremia = failure to excrete fixed acids + reduced ammoniagenesis.

2) Non–anion gap (hyperchloremic) metabolic acidosis: “Lose HCO₃⁻ or can’t excrete H⁺”

Think GI loss vs renal tubular acidosis (RTA).

RTA cheat table (very USMLE)

RTA type	Primary defect	Urine pH	Serum K⁺	Classic associations
Type 1 (distal)	Can’t secrete H⁺ (α-intercalated) → no new HCO₃⁻	> 5.5	Low	Kidney stones (↑pH), autoimmune (Sjogren), amphotericin B
Type 2 (proximal)	Can’t reabsorb HCO₃⁻ (prox tubule)	< 5.5 (after steady state)	Low	Fanconi, acetazolamide, multiple myeloma
Type 4 (hypoaldosteronism)	↓Aldo or resistance → ↓NH₄⁺ excretion	< 5.5 (often)	High	Diabetic nephropathy, ACEi/ARB, heparin, adrenal insufficiency

One-liner:

Type 1: can’t dump acid → urine stays basic
Type 2: dump bicarb early → later urine can acidify
Type 4: can’t make NH₄⁺ → hyperkalemic acidosis

Quick renal test tip:

Urine pH > 5.5 in metabolic acidosis screams distal (type 1) RTA.

3) Metabolic alkalosis: “Gain HCO₃⁻ or lose H⁺” and kidneys choose whether to keep it

A metabolic alkalosis persists only if kidneys are forced to hold onto HCO₃⁻.

Two big categories (chloride helps you decide):

Chloride-responsive (urine Cl⁻ low): volume depletion

Vomiting/NG suction (loss of HCl)
Post-diuretics (“contraction alkalosis”)
Responds to normal saline

Renal mechanism: Low volume → ↑RAAS → ↑Na⁺ reabsorption → ↑H⁺ secretion + ↑HCO₃⁻ reabsorption.

Chloride-resistant (urine Cl⁻ high): mineralocorticoid effect

Hyperaldosteronism, Cushing, Liddle
Severe hypokalemia (drives H⁺ into cells)

Renal mechanism: Aldosterone → ↑ENaC activity → lumen negative → ↑H⁺ secretion (α-intercalated) + ↑K⁺ secretion.

Rapid-fire high-yield one-liners (test-day glue)

Compensation never overshoots: if pH is normal but PaCO₂/HCO₃⁻ are abnormal → think mixed disorder.
Albumin correction prevents missing AG acidosis in sick patients.
Chronic respiratory acidosis (COPD) → high HCO₃⁻ via renal retention/new generation.
Chronic respiratory alkalosis (pregnancy, cirrhosis) → low HCO₃⁻ via renal loss.
Type 4 RTA is the hyperkalemic RTA (most commonly tested differentiator).

Pocket “Flowchart in 10 words” (shareable mnemonic)

“pH → driver → compensation → AG → delta → renal cause.”