Acid-Base Physiology
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Direct answer
Arterial pH 7.4 is defended by three lines: buffers within seconds, respiratory compensation within minutes, and renal correction over hours to days. The anchor numbers are pH 7.35-7.45, PaCO2 40 mm Hg and bicarbonate 24 mEq/L, tied by the Henderson-Hasselbalch equation pH = 6.1 + log of the 20:1 ratio of bicarbonate to dissolved CO2 (0.03 x PaCO2). Metabolic disturbances shift bicarbonate and are compensated by ventilation — Winter's formula predicts the expected PaCO2 as 1.5 x bicarbonate + 8, plus or minus 2 — while respiratory disturbances shift PaCO2 and are compensated renally: acute CO2 retention raises bicarbonate about 1 mEq/L per 10 mm Hg, and chronic retention about 3.5-4 per 10. The anion gap, normally about 12 plus or minus 4, then separates the metabolic acidoses into high-gap and normal-gap families.
What you must remember
- Normal panel: pH 7.35-7.45; PaCO2 35-45 mm Hg; HCO3 22-26 mEq/L; the 20:1 HCO3 to dissolved CO2 ratio is what holds pH at 7.4.
- Buffer hierarchy: bicarbonate is the principal extracellular buffer; phosphate and protein dominate intracellularly; plasma protein is the most abundant buffer overall; bone carbonate buffers chronic acid loads.
- Renal duty: about 4,320 mEq of filtered bicarbonate is reclaimed daily (roughly 85 per cent in the proximal tubule), plus titratable acid and ammonium excretion — ammonium generation can climb nearly 10-fold in chronic acidosis and is the adaptable arm.
- Compensation arithmetic: metabolic — expected PaCO2 = 1.5 x HCO3 + 8 (plus or minus 2). Respiratory acidosis: acute +1, chronic +3.5 to 4 mEq/L per 10 mm Hg rise; respiratory alkalosis: acute -2, chronic -5 per 10 mm Hg fall.
- Anion gap: Na minus (Cl + HCO3), normal 12 plus or minus 4; raised by ketones, lactate, renal failure, toxins (MUDPILES); normal-gap acidosis means diarrhoea or renal tubular acidosis.
- Delta ratio: rise in gap divided by fall in bicarbonate — less than 0.4 suggests a coexisting normal-gap acidosis, over 2 suggests a metabolic alkalosis riding along.
- Respiratory vs metabolic identity: if pH and PaCO2 move in the same direction the primary event is metabolic; opposite directions mean a primary respiratory problem.
Working through an arterial blood gas
Take pH 7.28, PaCO2 25 mm Hg, bicarbonate 12 mEq/L, sodium 140, chloride 100. First, acidosis. Second, pH and PaCO2 have moved in the same direction, so the primary process is metabolic. Third, is compensation adequate? Winter: 1.5 x 12 + 8 = 26, expected PaCO2 about 24-28, and the measured 25 sits inside — a appropriately compensated metabolic acidosis with no second disorder. Fourth, the gap: 140 minus (100 + 12) = 28, which is 16 above the midpoint of 12 — a high anion gap acidosis. In an Indian screening setting the differential narrows to diabetic ketoacidosis (a young patient, glucose 450, ketones), lactic acidosis from sepsis or metformin, or a toxin. Had the chloride been 112 instead, the gap would have been 16 — normal — pushing you toward diarrhoea or renal tubular acidosis, where the kidney or the gut is losing bicarbonate and chloride fills the space. Reading in this fixed order — pH, direction, compensation, gap — converts a six-mark puzzle into four quick steps.
The trap the NBE sets
The recurring trap is expecting too much from compensation. Physiological compensation never fully corrects the pH, and it never overshoots into alkalosis for a primary acidosis — if pH is 7.50 with a low bicarbonate and a low PaCO2, you are looking at two disorders, usually a metabolic acidosis plus a respiratory alkalosis, classic in salicylate poisoning or sepsis with renal failure. The second trap is the acute-versus-chronic arithmetic: a patient at PaCO2 80 from a two-day-old neuromuscular problem should have a bicarbonate near 28; a bicarbonate of 38 means the retention is chronic or an alkalosis coexists. Candidates also forget that acute respiratory acidosis moves pH about 0.08 per 10 mm Hg while chronic moves only 0.03 — the renal bicarbonate harvest blunts the swing.
Frequently asked questions
What is Winter's formula and when is it used?
Expected PaCO2 = 1.5 x HCO3 + 8 (plus or minus 2); in a metabolic acidosis, a measured PaCO2 outside this range signals an additional respiratory disorder.
How much does bicarbonate rise per 10 mm Hg of chronic CO2 retention?
About 3.5-4 mEq/L chronically, but only about 1 mEq/L acutely — the difference between buffered acute retention and renal compensation.
Which buffer is most important in the extracellular fluid?
Bicarbonate, because it pairs with an open system: CO2 is exhaled, so the pair can be regulated by both lungs and kidney.
What does a normal anion gap in a metabolic acidosis suggest?
Bicarbonate loss with chloride retention — diarrhoea, renal tubular acidosis, or carbonic anhydrase inhibitors — rather than an added acid.
Why does ammonium excretion matter in chronic acidosis?
Adaptive ammoniagenesis from glutamine lets the kidney excrete large amounts of H+ as NH4+, increasing nearly 10-fold and generating new bicarbonate in the process.