8 · Acid–Base Disorders

Every blood gas is worked in the same order — pH, primary process, compensation, anion gap, then the gap that closes the differential — and the exam questions are that algorithm stopped at different steps.

The numbers that anchor every gas

Carbon dioxide and bicarbonate are two faces of one buffer: CO₂ + H₂O ↔ H₂CO₃ ↔ H⁺ + HCO₃⁻. CO₂ behaves as a weak acid regulated by the lungs; HCO₃⁻ behaves as a weak base regulated by the kidney. An acid donates H⁺ and lowers the pH; a base (alkali) removes H⁺ and raises it. Pure water sits at pH 7.0.

Value	Normal	What it tells you
pH	7.35–7.45	<7.35 is acidosis (in extracellular fluid, acidemia); >7.45 is alkalosis (alkalemia)
pCO₂	35–45 mmHg (course lab sheet: 33–45)	Partial pressure of CO₂ in arterial or venous blood — the respiratory arm
HCO₃⁻	22–26 mEq/L (course lab sheet: 22–28)	The metabolic arm, set by the kidney
Anion gap	12	Na⁺ − (Cl⁻ + HCO₃⁻) — the unmeasured anions, mostly organic acids

A normal ABG reported as pH / pCO₂ / pO₂ / HCO₃ is 7.4 / 40 / 90 / 24 mEq/L. The chemistry beside it is the Chem 7 — Na⁺, K⁺, Cl⁻, CO₂ (serum bicarbonate), BUN, creatinine, glucose — without which no anion gap can be calculated. The Henderson–Hasselbalch equation and its modified Henderson form restate that pH is fixed by the ratio of HCO₃⁻ to pCO₂, which is why both arms are read together.

Two background rules travel with this material. The 60–40–20 rule: total body water is 60% of body weight (50% in women), intracellular fluid 40%, extracellular fluid 20%. Volume status is measured invasively by CVP and PCWP (pulmonary capillary wedge pressure); obtundation is the blunted consciousness severe disturbances produce.

⭐ The four numbers to memorize: 7.40 / 40 / 24 / 12 — pH, pCO₂, HCO₃⁻ and anion gap. Every formula in this section is written as a deviation from one of those four.

Acid–base disorders are more common in minority racial and ethnic groups, lower socioeconomic classes and males, who carry a higher burden of the diseases that cause them — but any patient with the right condition can develop one.

What the pH does to the patient

System	Acidosis	Alkalosis
Cardiovascular	Hypotension — decreased contractility lowers cardiac output and blood pressure, vasodilation lowers peripheral resistance, and severe acidosis becomes resistant to pressors. Myocardial irritability causes ventricular tachycardia	No effect on contractility, but vasoconstriction increases total vascular resistance. Also agitates the myocardium — VT, VF and SVT
CNS	Altered mental status from a decrease in cerebral volume; may induce coma	Altered mental status from neuronal hyperactivity → seizures or tetany → coma
Pulmonary	Increased respiratory rate → increased work of breathing → fatigue → respiratory failure	Decreased respiratory rate → hypoxemia
Metabolic	Hyperkalemia — H⁺ moves into cells and releases K⁺ into blood, causing arrhythmias. Hyperglycemia — H⁺ causes cellular insulin resistance	Hypokalemia and hypomagnesemia — less H⁺ means less K⁺ and Mg⁺ leaving cells. Hypocalcemia — with less free H⁺ to occupy albumin, Ca⁺⁺ binds it instead

⭐ The lethal pair: acidemia gives hyperkalemia plus a heart that will not answer pressors; alkalemia gives hypokalemia, hypomagnesemia and hypocalcemia with a myocardium primed for VT, VF and SVT. Both kill through the rhythm.

The four primary disorders

Respiratory disorders are changes in pCO₂, begin within minutes, and there can only ever be one at a time — a patient cannot simultaneously hypoventilate and hyperventilate. Metabolic disorders are changes in HCO₃⁻, take days, and several can coexist.

The direction rule is the whole of step 2 — SM.ORE: the Same direction for pH and HCO₃⁻ means Metabolic; the Opposite direction for pH and pCO₂ means REspiratory.

Disorder	pH	Primary change	Expected compensation	Causes
Respiratory acidosis	↓	↑ pCO₂ (>45) — less CO₂ exhaled, so blood CO₂ rises	Renal, hours to days: excrete more H⁺, reabsorb more HCO₃⁻	CNS depression (opioids, sedatives); neuromuscular disease affecting the diaphragm; obstructive lung disease
Respiratory alkalosis	↑	↓ pCO₂ (<35) — more CO₂ exhaled	Renal, hours to days: excrete less H⁺, reabsorb less HCO₃⁻	CNS hyperactivity — anxiety, fever, pain, salicylates, sepsis; hypoxemia — pneumonia, pulmonary edema, pulmonary embolism; liver disease
Metabolic acidosis	↓	↓ HCO₃⁻ (<22) — retaining H⁺ or losing HCO₃⁻	Pulmonary, minutes: low pH stimulates the CNS → ↑ respiratory rate, blowing off CO₂	Split by the anion gap — CATMUDPILES or HARDUP
Metabolic alkalosis	↑	↑ HCO₃⁻ (>26) — losing H⁺ or retaining HCO₃⁻	Pulmonary, minutes: high pH inhibits the CNS → ↓ respiratory rate, retaining CO₂	V.O.M.I.T. — see below

Compensation never overshoots and never fully corrects. Kidney and lung pull the pH back toward 7.40 but never past it — a pH on the other side of normal is a second primary disorder, not compensation.

The differentials, by mnemonic

Pattern	Mnemonic	Causes
High anion gap metabolic acidosis (AGMA), AG >12	C.A.T.M.U.D.P.I.L.E.S.	Carbon monoxide · Alcoholic ketoacidosis — the course slide reads aminoglycoside, but aminoglycosides cause acute tubular necrosis rather than an elevated gap · Toluene (glue sniffing) · Methanol · Uremia from significant AKI or renal failure · Diabetic ketoacidosis · Propylene glycol, paraldehyde · Isoniazid, iron, isopropyl alcohol · Lactic acidosis · Ethylene glycol (antifreeze) · Salicylates (aspirin)
Normal anion gap metabolic acidosis (NAGMA), AG <12	H.A.R.D.U.P.	H — the course mnemonic reads hypochloridemia from a large normal-saline load, though the mechanism is in fact hyperchloremia from the chloride load; some versions read hyperalimentation · Acetazolamide, which makes the kidney dump HCO₃⁻ (also adrenal insufficiency) · Renal tubular acidosis · Diarrhea and diuretics — loss of HCO₃⁻ · Ureteral diversion / ureteroenteric fistula · Pancreatic fistula
Metabolic alkalosis	V.O.M.I.T.	Vomiting — H⁺ loss · Overcorrection of hypercapnia in ventilated patients · Mineralocorticoid excess — aldosterone · Iatrogenic — giving the patient NaHCO₃ · Total volume loss — dehydration, blood loss, diuretics, laxative abuse
Exogenous toxin with a high osmolal gap	M.A.D.G.A.S.	Mannitol · Alcohols · Diatrizoate (imaging contrast) · Glycerol · Acetone · Sorbitol

The gap tells you which list to open: reciting CATMUDPILES for a patient whose gap is 9 wastes the question — that patient is on the HARDUP list.

Expected compensation — the formulas

Once the primary disturbance is named, ask whether the compensatory response is the size it should be. An inadequate or exaggerated response means a second primary disturbance is present.

Primary disorder	Expected compensation
Metabolic acidosis	Winter's formula: expected pCO₂ = (1.5 × HCO₃) + 8 ± 2. An alternative rule, pCO₂ = HCO₃ + 15, agrees with Winter's near a bicarbonate of 14 but diverges at low bicarbonate — at HCO₃ 8, Winter's predicts 20 and this rule 23. Use Winter's unless a question supplies the other
Metabolic alkalosis	Expected pCO₂ = 40 + [0.7 × (HCO₃ − 24)] ± 2
Respiratory acidosis — acute	Expected HCO₃ = 24 + [1 × (pCO₂ − 40)/10]
Respiratory acidosis — chronic	Expected HCO₃ = 24 + [3.5 × (pCO₂ − 40)/10]
Respiratory alkalosis — acute	Expected HCO₃ = 24 − [2 × (40 − pCO₂)/10]
Respiratory alkalosis — chronic	Expected HCO₃ = 24 − [5 × (40 − pCO₂)/10]

Winter's formula is also the fallback when no pCO₂ is provided. If the measured pCO₂ is above the Winter's range the patient is not blowing off enough CO₂ — a superimposed respiratory acidosis, classically the exhausted patient who can no longer sustain Kussmaul breathing; below the range means a superimposed respiratory alkalosis. For a primary respiratory process there is a fast acute check as well: a 10 mmHg change in pCO₂ should move the pH by about 0.08, and a larger swing means an added metabolic derangement.

⭐ Acute versus chronic respiratory acidosis: a pCO₂ of 60 predicts a bicarbonate of 26 if acute (24 + 2) but 31 if chronic (24 + 7). The COPD patient with a chronically high HCO₃ and near-normal pH is compensated, not normal — and dropping his CO₂ too fast on a ventilator strands that bicarbonate as a post-hypercapnic metabolic alkalosis.

The algorithm, step by step

Step 1 — Look at the pH. Below 7.35 is acidemia, above 7.45 is alkalemia. Caution: if the pH is normal, keep going — either nothing is wrong or compensation has already pulled the pH back, and only the pCO₂ and HCO₃⁻ say which.

Step 2 — Look at the pCO₂ and HCO₃⁻ and name the primary process. Apply SM.ORE. Even if the pCO₂ looks normal, continue — a normal-looking value inside an abnormal gas is often compensation caught mid-course. Then check that compensation against the formulas above.

Step 3 — If there is a metabolic acidosis, calculate the anion gap. AG = Na⁺ − (Cl⁻ + HCO₃⁻); normal 12. AG >12 = AGMA, open CATMUDPILES. AG <12 = NAGMA, open HARDUP.

Step 4 — If the gap is high, calculate the osmolal gap to separate an ingested toxin from an endogenous acid, and the delta ratio to expose a second metabolic disorder underneath.

Step 5 — If the gap is normal, calculate the urine anion gap to separate a gut cause from a kidney cause. For a primary metabolic alkalosis the equivalent branch point is the urine chloride.

⭐ Calculate the gap on every metabolic acidosis, without exception — and on any sick patient, because a gap of 20 or more means an organic acid is accumulating whatever the pH reads.

Step 3: the anion gap and its albumin correction

The anion gap measures the unmeasured anions, primarily organic acids. When an organic acid such as lactate or a ketoacid is added to the blood it consumes bicarbonate and leaves its own anion behind, so bicarbonate falls while chloride stays put and the gap widens. When bicarbonate is simply lost from the gut or the tubule, chloride is retained in its place, so bicarbonate falls but the gap stays normal — which is why NAGMA is also called a hyperchloremic acidosis.

Albumin is itself the largest unmeasured anion, so a hypoalbuminemic patient has a lower baseline gap and a real acidosis can look deceptively normal. Correct for it with the predictive anion gap = albumin × 3: a normal albumin of 4 g/dL gives 4 × 3 = 12, the familiar number. With an albumin of 2 g/dL the predicted gap is only 6, so a measured gap of 12 is double what it should be and is a real anion gap acidosis. Every 1 g/dL fall in albumin lowers the expected gap by about 3 mEq/L.

⭐ The classic miss: the malnourished or cirrhotic patient with an albumin of 2 and a "normal" gap of 12. Predict the gap from the albumin before calling it a NAGMA.

Step 4a: the osmolal gap and the delta–delta

Osmolal gap. Calculate the serum osmolality from the chemistry and subtract it from the measured osmolality:

Calculated osmolarity = (2 × Na) + glucose/18 + BUN/2.8, normally 285 mOsm/kg (280–295).
Osmolal gap = measured − calculated osmolality, normally <10 mOsm/L (10 ± 6).

A gap <10 points to an endogenous acid — lactate from sepsis or hypoperfusion, ketoacids from uncontrolled diabetes or malnutrition, uremic acids from kidney failure. A gap >10 means an exogenous osmotically active substance — the MADGAS list, above all methanol and ethylene glycol.

Delta ratio (delta–delta, or gap–gap analysis). This asks whether the rise in the anion gap accounts for the whole fall in bicarbonate — in a pure AGMA, every mEq of bicarbonate consumed is matched by a mEq of new unmeasured anion.

Delta ratio = (measured AG − 12) ÷ (24 − measured HCO₃)
<1 — pure AGMA
1–2 — mixed AGMA and NAGMA
>2 — AGMA plus a metabolic alkalosis

A second rule, which is not equivalent to the bands above, compares them by subtraction: ΔAG = measured AG − 12 versus ΔHCO₃ = 24 − measured HCO₃. A difference exceeding about 6 mEq/L means a second process. The two methods can disagree — a ratio inside the 1–2 band can still show a subtraction difference above 6: use the ratio bands when a ratio is asked for, and the subtraction rule when the two deltas are given separately. Note also that standard nephrology teaching assigns a ratio <1 to a concurrent non-gap acidosis and 1–2 to a pure gap acidosis — the reverse of the bands above. This course uses the bands above. ΔAG > ΔHCO₃ — bicarbonate is higher than the acid load explains, so an additional metabolic alkalosis (the ketoacidotic patient who has also been vomiting). ΔAG < ΔHCO₃ — bicarbonate has fallen further than the gap explains, so an additional non–anion gap acidosis (the same patient after days of diarrhea).

Do not use the delta ratio to decide whether an acidosis exists — it is a second-order test that only makes sense once the gap has said there is an AGMA.

Step 4b: the urine anion gap

When the gap is normal, ask whether the kidney is part of the problem or responding correctly. The kidney answers acid by excreting ammonium, which is not measured directly — but it leaves with chloride, so a urine chloride exceeding urine sodium plus potassium proves ammonium excretion is brisk.

Urine anion gap = urine Na + urine K − urine Cl; normally <0 (reference 0 ± 10).
Negative UAG — ammonium excretion is appropriate, so the kidney is innocent and the cause is gastrointestinal or iatrogenic: diarrhea, parenteral nutrition, high-volume chloride-containing fluids.
Positive UAG — ammonium excretion is impaired, meaning a renal tubular acidosis; serum potassium and urine pH then separate the types.

Type	Defect	Serum K⁺	Urine pH	Clue
I (distal)	↓ H⁺ secretion	Low	>5.5 (the algorithm branches at >5.3)	Sjögren syndrome, kidney stones
II (proximal)	↓ HCO₃⁻ reabsorption	Low	<5.5 (variable)	Multiple myeloma, Fanconi syndrome, acetazolamide
IV	Hypoaldosteronism	High	<5.5	Diabetes, NSAIDs, ACE inhibitors, sickle cell disease

Treatment of RTA is largely treatment of the underlying kidney disease — antibiotics for infection, restoring renal perfusion, removing the offending drug — and further sorting warrants nephrology consultation.

⭐ Negative urine gap, blame the gut; positive, blame the kidney. Days of watery diarrhea with a serum gap of 9 and a negative urine anion gap needs volume and time, not a renal work-up.

Metabolic alkalosis: the urine chloride branch

Metabolic alkalosis is sorted by one test — a spot urine chloride — because the answer decides whether saline will fix it.

Chloride-depletion (chloride-responsive), urine Cl <20 mEq/L: vomiting or nasogastric suction, diarrhea, chronic diuretics, post-hypercapnic alkalosis, bicarbonate infusion. The kidney is avidly reabsorbing chloride because the patient is volume- and chloride-depleted, and these improve with saline.
Non–chloride depletion (chloride-resistant), urine Cl >20 mEq/L: next check blood pressure and volume. If elevated, suspect mineralocorticoid excess and send plasma renin and aldosterone — low renin with high aldosterone is primary hyperaldosteronism; low renin with low aldosterone suggests Liddle or Cushing syndrome; high renin with high aldosterone suggests renal artery stenosis or malignant hypertension. Normal pressure with a persistently high urine chloride points to Bartter or Gitelman syndrome; a fluctuating value usually means diuretics. Saline will not correct these.

Hypokalemia perpetuates the alkalosis by driving H⁺ into cells, so potassium chloride added to the intravenous fluid repletes chloride and potassium at once.

⭐ Urine chloride <20 means give saline. Volume repletion restores chloride, switches off aldosterone and lets the kidney excrete the excess bicarbonate. Above 20, saline is the wrong answer and the work-up moves to blood pressure, renin and aldosterone.

Mixed disorders

Two or three simultaneous disorders can be present, but there can never be two primary respiratory disorders. Critically ill patients mix disorders often, and the tell is that HCO₃⁻ and pCO₂ deviate in opposite directions from normal. Three findings each demand a search for a second process: a compensation that misses its formula, a delta ratio outside the pure-AGMA band, and a pH that has crossed to the wrong side of normal.

Worked cases

Gas and chemistry	Steps	Answer
pH 7.47 / pCO₂ 29 / pO₂ 94 / HCO₃ 22; Na 140, K 4.0, Cl 106, CO₂ 22	pH >7.45 = alkalosis; pCO₂ 29 low, HCO₃ 22 normal — pH and pCO₂ moved opposite ways	Respiratory alkalosis, uncompensated
pH 7.42 / pCO₂ 29 / pO₂ 94 / HCO₃ 19; Na 140, K 4.0, Cl 110, CO₂ 19	pH 7.42 is normal, but pCO₂ 29 <35 and HCO₃ 19 <22 — the pH leans alkalotic and bicarbonate has fallen to meet it	Respiratory alkalosis with compensation — never stop at a normal pH
pH 7.26 / pCO₂ 60 / pO₂ 55 / HCO₃ 26; Na 140, K 4.0, Cl 104, CO₂ 26	pH <7.35 = acidosis; pCO₂ 60 >45, HCO₃ 26 normal — the kidney has not had time to respond	Respiratory acidosis, acute and uncompensated
pH 7.34 / pCO₂ 60 / pO₂ 55 / HCO₃ 30; Na 140, K 4.0, Cl 100, CO₂ 30	pH 7.34 is just acidemic; pCO₂ 60 >45 and HCO₃ 30 >26 — same pCO₂ as above, bicarbonate has climbed	Respiratory acidosis with compensation from HCO₃⁻, pH nearly restored
pH 7.25 / pCO₂ 27 / pO₂ 99 / HCO₃ 12; Na 140, K 4.0, Cl 96, CO₂ 12	Acidemic; pCO₂ 27 and HCO₃ 12 both low = metabolic acidosis. AG = 140 − (96 + 12) = 32. Delta ratio = 20/12 = 1.66	AGMA with a delta ratio of 1–2 → mixed AGMA and NAGMA
pH 7.50 / pCO₂ 48 / pO₂ 90 / HCO₃ 38; Na 135, K 3.6, Cl 85, CO₂ 38	pH >7.45 = alkalosis; pCO₂ 48 >45 and HCO₃ 38 >26 — pH and HCO₃ rose together	Metabolic alkalosis with respiratory compensation
pH 7.15 / pCO₂ 40 / pO₂ 55 / HCO₃ 15; Na 140, K 4.0, Cl 98, CO₂ 15	Acidemic; pCO₂ 40 normal, HCO₃ 15 low = metabolic acidosis. AG = 140 − (98 + 15) = 27. Delta ratio = 15/9 = 1.66. Winter's predicts pCO₂ 30.5 ± 2, so 40 is far too high	AGMA, mixed with NAGMA, and the failed respiratory compensation adds a respiratory acidosis

Case: the patient on metformin

A 65-year-old man with type 2 diabetes on metformin 1000 mg twice daily, hypertension and CKD stage 3 presents after four days of confusion, nausea, vomiting and weakness; his wife says his breathing has become fast and deep, "sighing a lot." BP 100/60, HR 115, RR 32 and labored, temperature 98.4°F, SpO₂ 97% on room air; disoriented, lethargic, dry mucous membranes, Kussmaul respirations. Labs: Na 130, K 6.1, Cl 94, HCO₃ 8, BUN 45, creatinine 3.1, glucose 115, lactate 12.4 mmol/L, pH 7.08.

Step 1–2: pH 7.08 is severe acidemia with a bicarbonate of 8 — metabolic acidosis; the elevated BUN and creatinine mark an AKI on top of his CKD. The Kussmaul breathing is the compensation; Winter's predicts pCO₂ = (1.5 × 8) + 8 = 20 ± 2.
Step 3: AG = 130 − (94 + 8) = 28, far above 12 — AGMA.
Step 4: working CATMUDPILES, two causes run at once — uremia from his CKD and rising BUN/creatinine, and the lactate of 12.4 confirming lactic acidosis from metformin his injured kidneys cannot clear.
Management: stop the metformin and address the AKI, which is worsening the uremia and impairing acid excretion. Give intravenous fluids (normal saline) to correct dehydration, improve renal perfusion and wash out lactate; add vasopressors if he stays hypotensive and intubate if respiratory muscles fatigue. For pH <7.1 sodium bicarbonate may be considered but is controversial and risks hypernatremia and hypocalcemia. Emergent hemodialysis is definitive — it removes lactate and metformin while correcting the acidemia and hyperkalemia. Repeat the ABG, lactate and chemistry, and educate the family about metformin in renal impairment.

Metformin plus AKI equals lactic acidosis until proven otherwise — and two CATMUDPILES causes can run in one patient, so finding the first does not excuse you from the second.

Case: the diarrhea patient (NAGMA)

A 35-year-old man with four days of watery diarrhea — 10–15 stools daily — is weak and lightheaded. HR 115, BP 98/62, RR 24; sunken eyes, dry mucous membranes, Kussmaul breathing, delayed capillary refill. Na 138, K 3.2, Cl 115, serum CO₂ 14, BUN 30, creatinine 1.5. ABG: pH 7.25, PaCO₂ 26, HCO₃ 13.

Primary process: low pH, low bicarbonate, low PaCO₂ — metabolic acidosis with respiratory compensation.
Anion gap: 138 − (115 + 14) = 9 — a NAGMA, and the chloride of 115 shows why it is called hyperchloremic.
Compensation: Winter's gives expected PaCO₂ = (1.5 × 14) + 8 ± 2 = 29 ± 2, i.e. 27–31 mmHg; the measured 26 sits just below that range — close enough that it is read as appropriate compensation rather than a second process.
Management: hypovolemia first, so aggressive fluid resuscitation. Normal saline is chloride-rich and worsens a hyperchloremic acidosis — a balanced crystalloid (lactated Ringer's, Plasma-Lyte) is better, its lactate or acetate being metabolized to bicarbonate. Severe acidosis (pH <7.2) or a bicarbonate below 16–18 mEq/L may warrant sodium bicarbonate: deficit = 0.5 × weight (kg) × (24 − measured HCO₃) = 0.5 × 70 × 10 = 350 mEq for a 70 kg patient — give half slowly and recheck. Add loperamide to stop ongoing bicarbonate loss and follow the potassium.

Case: the vomiting patient (metabolic alkalosis)

A 45-year-old woman with alcohol use disorder has five days of vomiting and 24 hours of no intake. HR 105, BP 100/65 with orthostatic change, RR 12 and shallow. Na 136, K 2.9, Cl 85, serum CO₂ 35, BUN 28, creatinine 1.2. ABG: pH 7.52, PaCO₂ 48, HCO₃ 36.

Primary process: pH and bicarbonate both high — metabolic alkalosis, with the elevated PaCO₂ the lung hypoventilating to compensate.
Compensation: expected PaCO₂ = 0.7 × (36 − 24) + 40 ± 2 = 48.4 ± 2 (46.4–50.4); the measured 48 falls inside it, so no additional respiratory disorder.
Branch point: urine chloride 9 mEq/L. Below 20 means chloride-responsive alkalosis from volume depletion — here, gastric acid lost by vomiting.
Management: 0.9% normal saline restores volume and supplies the chloride that lets the kidney excrete the excess bicarbonate, and potassium chloride is added because the hypokalemia drives H⁺ into cells and perpetuates the alkalosis. Stop the vomiting with ondansetron, consider a proton pump inhibitor or H₂-blocker, and address the alcohol use disorder. In resistant cases acetazolamide increases renal bicarbonate excretion; intravenous hydrochloric acid is reserved for life-threatening alkalosis (pH >7.6).

Note the mirror image: the diarrhea patient loses bicarbonate from below and turns acidemic, the vomiting patient loses acid from above and turns alkalemic. Both are hypovolemic and hypokalemic — the right fluid differs.

Case: diabetic ketoacidosis

A 28-year-old man with type 1 diabetes ran out of insulin two days ago: vomiting, abdominal pain, polyuria, lethargy. HR 118, BP 90/58, RR 32; dry mucous membranes, fruity odor, Kussmaul breathing. Na 132, K 5.5, Cl 98, serum CO₂ 8, glucose 650, BUN 35, creatinine 1.8. ABG: pH 7.15, PaCO₂ 24, HCO₃ 7. Serum ketones large; lactate 1.2 mmol/L.

Anion gap: 132 − (98 + 8) = 26 — an AGMA from ketoacids.
Compensation: Winter's gives (1.5 × 8) + 8 ± 2 = 20 ± 2 (18–22). The measured 24 is higher than expected — a superimposed respiratory acidosis in a patient too exhausted to sustain full compensation.
Delta gap: (26 − 12) − (24 − 8) = −2. Gap rise and bicarbonate fall track each other, so this is a pure high anion gap acidosis.
Etiology: type 1 diabetes, glucose 650 and large ketones make DKA the answer; the normal lactate of 1.2 excludes lactic acidosis.
Management: fluids first — 1–2 L of 0.9% saline in the first hour, then 0.45% saline with potassium. Then a continuous intravenous regular insulin infusion whose goal is to close the anion gap (<12), not to normalize the glucose; when glucose falls below 250 mg/dL add dextrose so insulin can continue. The potassium of 5.5 conceals a total-body deficit — insulin drives it into cells, so recheck often and replace once it reaches the normal range. Routine bicarbonate is not recommended in DKA; reserve it for pH below about 6.9–7.0 with instability. Recheck glucose, electrolytes and the gap every 2–4 hours.

In DKA the anion gap is the endpoint, not the glucose. Keep insulin running until the gap closes, adding dextrose to protect the glucose — stopping at a normal glucose leaves the ketoacidosis unresolved.

Case: when every gap matters at once

A 48-year-old with type 2 diabetes is admitted with acute confusion and several days of diarrhea; afebrile, normotensive. ABG: pH 7.30, PaCO₂ 25. Serum: Na 148, K 3.2, Cl 104, HCO₃ 10, BUN 35, creatinine 1.8, glucose 360, measured osmolality 330 mOsm/kg.

Primary process: pH and PaCO₂ both decreased → metabolic acidosis.
Compensation: expected pCO₂ = HCO₃ + 15 = 25, exactly the measured value — appropriate.
Anion gap: 148 − (104 + 10) = 34, markedly elevated — ketoacids the likely cause.
Osmolal gap: calculated = (2 × 148) + 360/18 + 35/2.8 = 328.5; measured 330 − 328.5 = 1.5, under 10 — an endogenous acid, so no toxic alcohol to chase.
Gap–gap: ΔAG = 34 − 12 = 22 versus ΔHCO₃ = 24 − 10 = 14 — ΔAG exceeds ΔHCO₃ by 8, so an additional metabolic alkalosis is present from the preceding vomiting and diarrhea. The conclusion is an endogenous anion gap acidosis (DKA with AKI) plus a metabolic alkalosis, and hydration with reinitiated insulin corrected both.

A companion case makes the opposite point. A 56-year-old with COPD and a week of nausea, vomiting and diarrhea: pH 7.52, PaCO₂ 45; Na 145, K 3.2, Cl 98, HCO₃ 38; spot urine chloride <10. The primary process is metabolic alkalosis, but expected pCO₂ = 40 + [0.7 × (38 − 24)] = 49.8, and the measured 45 is below it — he is hyperventilating beyond what compensation calls for, so a concurrent respiratory alkalosis is present. The urine chloride under 20 confirms a chloride-depletion alkalosis, and both resolved with hydration.

⭐ Compensation is a measurement, not an assumption. A pCO₂ that merely moves the right way proves nothing — run the formula, and when the measured value misses the calculated range, name the second disorder.

Treating the disturbance

Treat the cause, not the number. Stopping the metformin, restoring perfusion, replacing insulin, halting the vomiting or diarrhea is what corrects the pH.
Volume first in almost every metabolic disorder. Hypovolemia runs through the AGMA, the NAGMA and the chloride-responsive alkalosis alike, and repletion alone often normalizes the gas.
Match the fluid to the disorder. Chloride-rich normal saline is right for a chloride-responsive alkalosis and wrong for a hyperchloremic NAGMA, where a balanced crystalloid is preferred — large saline volumes are themselves a cause of normal-gap acidosis.
Sodium bicarbonate is a rescue, not a routine. It has not improved outcomes and can cause paradoxical intracellular acidosis, hypocalcemia and hypernatremia; reserve it for severe acidemia (roughly pH <7.1, below 6.9–7.0 in DKA with instability) and give half the deficit slowly.
Dialysis is definitive when a dialyzable toxin, lactic acidosis, refractory acidemia and hyperkalemia coexist with kidney failure.
Escalate when the algorithm stalls — complex or mixed pictures, and any case not improving as predicted, warrant nephrology consultation.