SN7 SHORT NOTE 5M ★ High-yield

Define buffers. Describe the buffer systems of the body and the Henderson–Hasselbalch equation.

Biochemistry · 1st Professional — Pre-Clinical

Definition and Mechanism

A buffer is a solution that resists a change in pH on addition of acid or alkali. It consists of a weak acid and its conjugate base (or a weak base and its conjugate acid).

Buffering is most effective when pH = pK, where the acid and base forms are present in equal amounts; the useful range is about pK ± 1
Henderson–hasselbalch equation — pH = pK + log ([conjugate base] / [acid]). For the bicarbonate system, pH = 6.1 + log ([HCO3−] / 0.03 × pCO2)
Normal ratio is 20 : 1 of bicarbonate to carbonic acid, which gives a pH of 7.4; it is the ratio, not the absolute values, that determines pH — which is why compensation works

Buffer Systems of the Body

System	Location and share	Features
Bicarbonate	Extracellular; about 65% of buffering capacity	The most important, despite a pK of 6.1 being far from 7.4, because it is an open system — CO2 is removed by the lungs and bicarbonate regulated by the kidney, so both components are independently adjustable
Haemoglobin	Red cells; the major intracellular blood buffer	The imidazole group of histidine has a pK near 7; DEOXYhaemoglobin is a better buffer than oxyhaemoglobin, which is the basis of the isohydric transport of CO2
Phosphate	Intracellular and urinary	PK 6.8, close to physiological pH; the chief urinary buffer, forming titratable acidity
Protein	Intracellular and plasma	Histidine, cysteine and terminal groups; a large reservoir intracellularly
Ammonia	Renal tubule	NH3 traps H+ as NH4+, which cannot diffuse back; the adaptive mechanism in chronic acidosis
Bone	Long term	Carbonate and phosphate exchange — which is why chronic acidosis causes bone demineralisation

CLINICAL PEARL

The bicarbonate system is the most important buffer in the body despite having the wrong pK for the job. A pK of 6.1 is more than a unit from pH 7.4, which should make it a poor buffer. It works because it is open at both ends — the lungs blow off CO2 and the kidney reclaims or excretes bicarbonate, so the system is continuously regenerated rather than being consumed. A closed buffer of the same pK would be almost useless.

Compensation and the Anion Gap

Respiratory compensation is rapid (minutes to hours) — ventilation alters pCO2 to correct a metabolic disturbance
Renal compensation is slow (hours to days) — bicarbonate reabsorption, titratable acid and ammonium excretion correct a respiratory disturbance
Compensation never fully corrects the pH; overcorrection indicates a second, independent disorder
Anion gap = Na+ − (Cl− + HCO3−), normally 8 to 16 mmol/L; it represents unmeasured anions, chiefly albumin
High anion gap metabolic acidosis — ketoacidosis, lactic acidosis, renal failure, and the toxic alcohols and salicylate
Normal anion gap (hyperchloraemic) acidosis — diarrhoea, renal tubular acidosis, and acetazolamide; here bicarbonate is lost and replaced by chloride
Correct the gap for albumin, adding about 2.5 mmol/L for every 10 g/L the albumin falls; otherwise a significant acidosis is missed in a hypoalbuminaemic patient

Applied Aspects

Interpret arterial blood gases in order — pH first (acidaemia or alkalaemia), then pCO2 and bicarbonate to identify the primary disorder, then whether compensation is appropriate, then the anion gap
Calculate the anion gap in every metabolic acidosis; it separates two entirely different groups of causes and directs the investigation
Treat the underlying cause rather than the number; giving bicarbonate in diabetic ketoacidosis or lactic acidosis is rarely helpful and may cause paradoxical intracellular acidosis and hypokalaemia
Remember potassium moves with acid-base; acidosis drives potassium out of cells, so a normal potassium in diabetic ketoacidosis conceals a large total-body deficit that will unmask itself with treatment
A mixed disorder is common in the sick patient, and the compensation rules are what reveal it — a pCO2 that is not what the bicarbonate predicts means more than one process is present

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