Acid-Base Disorders

High anion gap metabolic acidosis — excess acid production or retention

• Increased organic acid generation: diabetic, alcoholic, and starvation ketoacidosis (insulinopenia/glucagon excess drives ketogenesis); type A lactic acidosis from hypoperfusion (shock, mesenteric ischemia, seizure); type B lactic acidosis without hypoxia (metformin accumulation, linezolid, propofol infusion syndrome, thiamine deficiency, malignancy)
• Toxic ingestions: methanol → formic acid; ethylene glycol → glycolic/oxalic acid; propylene glycol (IV lorazepam diluent); salicylates produce a mixed picture
• Failure of acid excretion: uremia in advanced CKD, where sulfate and phosphate anions accumulate

Normal anion gap (hyperchloremic) acidosis — bicarbonate loss or impaired H+ handling

• GI bicarbonate loss: diarrhea, pancreatic or biliary fistula, ureteral diversion
• Renal loss/dysfunction: proximal (type 2) and distal (type 1) RTA, type 4 RTA from hypoaldosteronism, carbonic anhydrase inhibitors, large-volume normal saline resuscitation

Metabolic alkalosis

• Chloride-responsive: vomiting, nasogastric suction, loop/thiazide diuretics, post-hypercapnic state
• Chloride-resistant: primary hyperaldosteronism, Cushing syndrome, licorice, Bartter and Gitelman syndromes, severe hypokalemia

Respiratory disorders by mechanism

• Acidosis: depressed drive (opioids, benzodiazepines, obesity hypoventilation, brainstem lesion), neuromuscular failure (Guillain–Barré, myasthenic crisis, ALS), obstructive disease (COPD, status asthmaticus), chest wall restriction (kyphoscoliosis, flail chest)
• Alkalosis: hypoxemic drive (pulmonary embolism, pneumonia, altitude), direct medullary stimulation (sepsis, pain/anxiety, salicylates, progesterone in pregnancy, hepatic encephalopathy), iatrogenic overventilation

Risk factors examiners plant

• Modifiable: alcohol use disorder, opioid/sedative use, diuretic misuse or bulimia, metformin continued during AKI or contrast exposure, smoking (COPD), obesity, poorly controlled diabetes — the ADA Standards of Care flag insulin omission and intercurrent illness as the dominant DKA precipitants
• Non-modifiable: CKD (KDIGO notes metabolic acidosis emerges as GFR falls), inherited tubulopathies, older age with reduced renal reserve, pregnancy (a physiologic chronic respiratory alkalosis, not pathology)

Buffer Systems

• Bicarbonate buffer system (HCO3−/H2CO3) is the most important extracellular buffer; carbonic acid (H2CO3) rapidly equilibrates with CO2 and H2O via the reaction: CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3−
• Phosphate buffer (HPO4²−/H2PO4−) and protein buffers (including hemoglobin) provide additional buffering capacity
• Buffers work within seconds but cannot eliminate acid/base loads

Respiratory Compensation

• The respiratory system eliminates volatile acid (CO2) through increased or decreased minute ventilation
• Medullary chemoreceptors sense changes in PaCO2 and pH to trigger appropriate ventilatory responses
• Respiratory compensation occurs within minutes to hours and can correct pH but not return HCO3− to normal

Renal Compensation

• The kidneys regulate HCO3− reabsorption (proximal tubule) and H+ secretion (collecting duct)
• Renal compensation occurs over hours to days and is the most powerful long-term mechanism
• The kidney can return HCO3− toward normal and restore acid-base status

Primary Disorders and Compensation

• Metabolic acidosis → respiratory compensation (↓ PaCO2 via hyperventilation)
• Metabolic alkalosis → respiratory compensation (↑ PaCO2 via hypoventilation)
• Respiratory acidosis → renal compensation (↑ HCO3− reabsorption)
• Respiratory alkalosis → renal compensation (↓ HCO3− reabsorption)

Metabolic Acidosis

• Kussmaul respirations (deep, labored breathing) – classically seen in diabetic ketoacidosis; occurs when pH <7.1–7.2
• Fatigue, malaise, and generalized weakness
• Nausea, vomiting, and anorexia; abdominal pain if severe
• Altered mental status, confusion, or lethargy in severe cases (pH <7.15)
• Cardiovascular instability: hypotension, decreased cardiac contractility, arrhythmias

Metabolic Alkalosis

• Hypokalemia symptoms: muscle weakness, cramping, fatigue
• Tetany, paresthesias (due to hypocalcemia from decreased ionized calcium at higher pH)
• Altered mental status, confusion, or irritability
• Cardiac arrhythmias (especially with concurrent hypokalemia)
• Hypoventilation may be present as respiratory compensation but is often blunted

Respiratory Acidosis

• Headache and flushed appearance (from CO2 vasodilation)
• Dyspnea, tachypnea, or use of accessory muscles (if acute and compensatory)
• Altered mental status: confusion, drowsiness, obtundation ("CO2 narcosis") when severe
• Papilledema may be present due to cerebral vasodilation
• Tremor ("asterixis")

Respiratory Alkalosis

• Lightheadedness, dizziness
• Paresthesias (perioral and in extremities) and tetany from hypocalcemia
• Anxiety, palpitations, sense of impending doom
• Syncope in severe cases
• Often asymptomatic if mild

Arterial Blood Gas (ABG) Analysis – The Foundation

• Obtain ABG (not venous) for accurate assessment of oxygenation and acid-base status
• Record: pH, PaCO2, HCO3−, PaO2, SaO2
• Use a systematic approach to interpretation:

Step 1: Identify the Primary Disorder

• Determine if pH is low (acidemia) or high (alkalemia)
• Identify which parameter (PaCO2 or HCO3−) is abnormal in the same direction as pH:
• Low pH + low HCO3− = metabolic acidosis (primary)
• Low pH + high PaCO2 = respiratory acidosis (primary)
• High pH + high HCO3− = metabolic alkalosis (primary)
• High pH + low PaCO2 = respiratory alkalosis (primary)

Step 2: Assess Appropriateness of Compensation

• Use predicted compensation formulas to determine if respiratory/renal response is appropriate:

For Metabolic Acidosis (Winter's Formula)

• Expected PaCO2 = 1.5 × [HCO3−] + (±2)
• If actual PaCO2 is higher than expected → concurrent respiratory acidosis is present
• If actual PaCO2 is lower than expected → concurrent respiratory alkalosis is present

For Metabolic Alkalosis

• Expected PaCO2 = 40 + 0.6 × ([HCO3−] − 24) (±2)
• Most metabolic alkalosis patients cannot hyperventilate sufficiently, so respiratory compensation is often inadequate

For Respiratory Acidosis (Acute vs. Chronic)

• Acute: HCO3− increases by 1 mEq/L for every 10 mmHg increase in PaCO2
• Chronic: HCO3− increases by 3–4 mEq/L for every 10 mmHg increase in PaCO2
• Helps distinguish acute vs. chronic lung disease

For Respiratory Alkalosis

• Acute: HCO3− decreases by 2 mEq/L for every 10 mmHg decrease in PaCO2
• Chronic: HCO3− decreases by 3–5 mEq/L for every 10 mmHg decrease in PaCO2

Step 3: Calculate Anion Gap (if metabolic acidosis)

• Anion Gap (AG) = [Na+] − ([Cl−] + [HCO3−])
• Normal AG = 8–12 mEq/L (varies by lab; some labs use 10–14)
• High AG metabolic acidosis (AG >12) suggests addition of unmeasured anions (organic acids)
• Mnemonics: MUDPILES (Methanol, Uremia, Diabetic ketoacidosis, Propylene glycol, Isoniazid, Lactic acid, Ethylene glycol, Salicylates)
• Normal AG metabolic acidosis (AG 8–12) suggests HCO3− loss or H+ retention without organic acid accumulation
• Causes: diarrhea (HCO3− loss), renal tubular acidosis (H+ retention), ureterosigmoidostomy

Step 4: Delta Gap (if high AG metabolic acidosis)

• ΔAG = Actual AG − Normal AG (assume 12)
• Compare ΔAG to decrease in HCO3− (24 − actual HCO3−):
• ΔAG = ΔHCO3− → isolated high AG metabolic acidosis
• ΔAG > ΔHCO3− → concurrent metabolic alkalosis
• ΔAG < ΔHCO3− →

Immediate stabilisation

• Airway, breathing, circulation first: severe acidemia blunts myocardial contractility and causes catecholamine resistance; if the patient is in arrest, follow AHA ACLS — defibrillate ventricular fibrillation / pulseless VT and treat the acidosis by restoring perfusion, not by pushing bicarbonate reflexively
• Treat the cause, not the number: fluid resuscitation and source control for lactic acidosis (Surviving Sepsis Campaign), naloxone for opioid-induced hypercapnia, ventilation for neuromuscular failure

Disorder-specific first-line therapy

• DKA: isotonic crystalloid, IV regular insulin infusion, and potassium repletion — per the ADA Standards of Care, hold insulin until K+ exceeds ~3.3 mEq/L, and reserve sodium bicarbonate for pH <6.9
• Toxic alcohols: alcohol dehydrogenase inhibitor — fomepizole — is preferred over ethanol, with cofactors (folate for methanol; thiamine and pyridoxine for ethylene glycol) and urgent hemodialysis for end-organ toxicity or severe acidemia, per American Academy of Clinical Toxicology guidance
• Salicylate toxicity: alkali therapy — sodium bicarbonate infusion with aggressive potassium repletion — to alkalinize serum and urine and trap salicylate; hemodialysis for altered mental status, pulmonary edema, or renal failure, consistent with EXTRIP workgroup recommendations
• Chronic metabolic acidosis of CKD: oral alkali — sodium bicarbonate tablets — when serum bicarbonate is persistently low, per KDIGO
• Chloride-responsive metabolic alkalosis (urine Cl− low): isotonic saline plus KCl; chloride-resistant (urine Cl− high): treat the mineralocorticoid excess, e.g. an MRA such as spironolactone
• Respiratory acidosis in COPD exacerbation: noninvasive positive-pressure ventilation is first-line per GOLD, with titrated oxygen to an SpO2 of roughly 88–92%

Escalation and definitive care

• Renal replacement therapy for refractory acidemia with AKI, dialyzable toxin, or volume overload
• Acetazolamide for diuretic-associated alkalosis with volume overload; HCl infusion via central line is a last resort

Contraindicated or discouraged

• Routine bicarbonate in lactic acidosis with pH above roughly 7.15 (Surviving Sepsis Campaign suggests against it)
• Paper-bag rebreathing for hyperventilation — risks hypoxemia and masks pulmonary embolism
• Abrupt normalization of PaCO2 in chronic hypercapnia (post-hypercapnic alkalosis, seizures)

Complications of severe acidemia

• Cardiovascular collapse (emergency): H+ impairs myofilament calcium responsiveness and downregulates adrenergic receptors → depressed contractility, arteriolar vasodilation, and vasopressor-refractory hypotension; signalled by rising lactate despite adequate pressors
• Arrhythmia and hyperkalemia (emergency): mineral (non-gap) acidoses drive K+ out of cells more than organic acidoses; peaked T waves or a widening QRS is the tell
• CNS depression: obtundation and coma; in chronic respiratory acidosis, asterixis and papilledema from cerebral vasodilation
• Chronic acidosis of CKD: buffering by bone releases calcium and phosphate → demineralization, plus muscle catabolism and accelerated GFR decline — the rationale KDIGO gives for alkali therapy

Complications of alkalemia

• Tetany and seizures: alkalosis increases albumin binding of calcium → falling ionized calcium; Chvostek and Trousseau signs appear with perioral paresthesias
• Reduced tissue oxygen delivery: leftward shift of the oxyhemoglobin dissociation curve plus cerebral vasoconstriction → syncope, and in the ventilated patient, hypocapnia-induced cerebral ischemia
• Hypokalemia with arrhythmia: transcellular K+ shift compounds renal losses

Complications of therapy

• Sodium bicarbonate: generated CO2 crosses the blood–brain barrier faster than HCO3− → paradoxical intracellular/CSF acidosis; also hypernatremia, volume overload, worsened hypokalemia, and ionized hypocalcemia causing tetany
• DKA treatment: cerebral edema (emergency, chiefly in children) from rapid osmolar shifts — a declining sensorium or bradycardia with hypertension after initial improvement; also insulin-driven hypokalemia and hypoglycemia, and a hyperchloremic non-gap acidosis from large-volume saline
• Over-rapid ventilatory correction of chronic hypercapnia: retained renal bicarbonate is unmasked → post-hypercapnic metabolic alkalosis with seizures
• Intubating a salicylate-poisoned patient: loss of compensatory hyperventilation collapses the pH and can precipitate death — a recognized peri-intubation catastrophe
• Ethylene glycol: calcium oxalate crystal deposition → AKI; methanol: optic neuropathy and permanent blindness

• A normal pH does not exclude disease: a normal pH with a widened anion gap, or with wildly abnormal PaCO2 and HCO3−, means a mixed disorder. Always calculate the gap even when pH looks fine.
• Salicylate poisoning is the classic mixed picture: primary respiratory alkalosis (direct medullary stimulation) plus high anion gap metabolic acidosis. Tinnitus, tachypnea, and fever in an adult with a normal-ish pH is the stem. Best next step is a salicylate level plus sodium bicarbonate for serum and urinary alkalinization; do not intubate casually.
• Osmolar gap plus anion gap acidosis = toxic alcohol. Oxalate crystals and AKI point to ethylene glycol; visual blurring or snowfield vision points to methanol. Single best next step is fomepizole, then dialysis.
• Urine anion gap sorts a normal-gap acidosis: negative (neGUTive) means intact renal NH4+ excretion and a GI cause such as diarrhea; positive means renal tubular acidosis. Type 1 gives urine pH >5.5 with hypokalemia and calcium phosphate stones; type 4 is the hyperkalemic one, classically diabetic nephropathy.
• Vomiting or NG suction produces hypochloremic, hypokalemic metabolic alkalosis with paradoxical aciduria; urine chloride is low and the patient is saline-responsive. High urine chloride redirects you to hyperaldosteronism, Bartter, or Gitelman.
• Winter's formula is the single most tested calculation: if measured PaCO2 exceeds predicted, a superimposed respiratory acidosis has been missed — a frequent reason an intubated patient decompensates.
• Common distractor — bicarbonate for DKA. The ADA Standards of Care reserve it for pH below 6.9; the answer in most DKA stems is fluids, insulin infusion, and potassium, with insulin withheld until K+ is repleted.
• Second common distractor — treating the number in lactic acidosis. The Surviving Sepsis Campaign directs you to perfusion and source control, not alkali, at moderate pH values.