10.4 — Acid–Base Balance

Blood pH is held between 7.35 and 7.45. That is a range of 0.1 pH unit, which sounds trivial until you remember that pH is logarithmic — a range of 0.1 is a variation of about 26 percent in hydrogen ion concentration. Outside 6.8 to 7.8 is generally incompatible with life.

Meanwhile you produce about 15,000 millimoles of carbon dioxide a day, which becomes acid in water, plus about 70 millimoles of fixed acid from metabolism. You generate an enormous acid load daily and your pH does not move.

Three systems do it, operating on three timescales.

Why it matters

Because proteins are pH-sensitive. Enzyme active sites depend on the charge of specific amino acid side chains (Chapter 1.3), and changing pH changes those charges. A pH shift of a few tenths alters the activity of essentially every enzyme in the body at once.

And it changes ion binding. Alkalosis increases calcium binding to albumin, lowering the free calcium and causing the tingling and spasms of Chapter 8.5. Acidosis drives potassium out of cells, raising blood potassium.

So an acid–base disturbance is never a local problem.

The three defences

1. Buffers — instantaneous.

A buffer is a weak acid and its conjugate base together, which can absorb or release hydrogen ions with minimal pH change.

The bicarbonate system is the most important, and it is the one worth understanding fully:

\mathrm{CO_2} + \mathrm{H_2O} \rightleftharpoons \mathrm{H_2CO_3} \rightleftharpoons \mathrm{H^+} + \mathrm{HCO_3^-}

On its own, bicarbonate would be a mediocre buffer — its dissociation constant is not well matched to blood pH. What makes it excellent is that both ends are independently controlled by organs.

The lungs control the CO₂ on the left. The kidneys control the bicarbonate on the right. A buffer whose components can both be adjusted at will is far more powerful than the chemistry alone suggests, and this is the reason evolution settled on it.

Other buffers: proteins, especially haemoglobin (Chapter 8.4); phosphate, important inside cells and in urine; and bone, which is the largest buffer reserve of all. Chronic acidosis is buffered partly by dissolving bone mineral, which is why chronic kidney disease causes bone disease and why children with untreated renal tubular acidosis fail to grow.

2. The lungs — minutes.

Changing ventilation changes CO₂, which changes pH within minutes (Chapter 8.5).

More ventilation blows off CO₂ and raises pH. Less ventilation retains CO₂ and lowers pH.

The response is fast and powerful but limited — you can only breathe so hard for so long, and it cannot correct the underlying problem.

3. The kidneys — hours to days.

The definitive system, and the slow one.

Reabsorbing bicarbonate. Almost all filtered bicarbonate is reclaimed in the proximal tubule — about 4,500 mmol a day. Losing it would be catastrophic, and this reclamation is essentially the first job.

Excreting hydrogen ions. But urine cannot go below about pH 4.5, so free hydrogen ions alone could only account for a tiny fraction of the load. The kidney therefore excretes acid attached to buffers.

Phosphate in the tubule accepts a hydrogen ion.

And ammonia is the adjustable route. Kidney cells make ammonia from glutamine, secrete it into the tubule, where it captures a hydrogen ion to become ammonium and is trapped there. Ammonia production can be increased several-fold over days, and this is the main way the kidney adapts to a sustained acid load.

Generating new bicarbonate. Every hydrogen ion excreted with a buffer generates a new bicarbonate that enters the blood.

The four disorders

Two axes: is it an acidosis or an alkalosis, and is the cause respiratory or metabolic?

	Low pH (acidosis)	High pH (alkalosis)
Respiratory	CO₂ high	CO₂ low
Metabolic	Bicarbonate low	Bicarbonate high

And the compensation always moves the other value in the same direction as the primary change. This is the single most useful rule for reading a blood gas.

If the primary problem is a high CO₂, the kidney raises the bicarbonate.If the primary problem is a low bicarbonate, the lungs lower the CO₂.

Compensation never fully corrects the pH — it moves it toward normal but not past it, and usually not all the way. So if the pH is completely normal with abnormal CO₂ and bicarbonate, suspect two disorders rather than perfect compensation.

Respiratory acidosis

CO₂ retention — hypoventilation.

Causes: COPD, severe asthma, opioid overdose, neuromuscular weakness, chest wall problems, and exhaustion.

Acute compensation is minimal — the kidney takes 3 to 5 days. This is why an acute rise in CO₂ produces a dangerously low pH while a chronic one does not. A patient with long-standing COPD may have a CO₂ of 8 kPa with a nearly normal pH, because the kidney has raised the bicarbonate over years. The same CO₂ appearing acutely would give a pH of about 7.2.

Comparing pH with CO₂ therefore distinguishes acute from chronic, and it changes the urgency entirely.

Respiratory alkalosis

CO₂ blown off — hyperventilation.

Causes: anxiety, pain, fever, sepsis, pulmonary embolism, high altitude, liver failure, aspirin overdose, and mechanical over-ventilation.

And this deserves emphasis: a hyperventilating patient is not necessarily anxious. Respiratory alkalosis is one of the earliest changes in sepsis and in pulmonary embolism, and attributing it to anxiety without excluding those is a well-recognised error.

Metabolic acidosis

The most clinically important, and the anion gap divides it into two useful groups.

The anion gap is a bookkeeping calculation:

\text{Anion gap} = [\mathrm{Na^+}] - [\mathrm{Cl^-}] - [\mathrm{HCO_3^-}]

Normally 8 to 16 mmol/L. The gap exists because the measured cations exceed the measured anions — the difference is made up by unmeasured anions, mostly albumin.

A raised gap means an unmeasured acid has been added. A normal gap means bicarbonate has been lost and chloride has replaced it.

Raised anion gap acidosis — an acid has been added. The mnemonic MUDPILES covers it: Methanol, Uraemia, Diabetic ketoacidosis, Propylene glycol, Iron and Isoniazid, Lactic acidosis, Ethylene glycol, Salicylates.

The two that matter most in practice are lactic acidosis and ketoacidosis.

Lactic acidosis means tissue is not getting enough oxygen (Chapter 1.6) — shock, sepsis, severe hypoxia, or ischaemic bowel. A raised lactate is one of the strongest predictors of death in an acutely unwell patient, and it is measured routinely for that reason.

Diabetic ketoacidosis — Chapter 18.7.

Normal anion gap acidosis — bicarbonate has been lost. Diarrhoea (which loses bicarbonate-rich intestinal fluid), renal tubular acidosis, and large volumes of normal saline (Chapter 10.3).

The respiratory compensation is visible and is a clinical sign. Deep sighing breathing — Kussmaul respiration — is the body blowing off CO₂ to compensate, and it is one of the classic findings in diabetic ketoacidosis. A person breathing deeply and rapidly without lung disease has a metabolic acidosis until proven otherwise.

Metabolic alkalosis

Causes: vomiting or nasogastric suction (losing stomach acid, Chapter 9.2), diuretics, excess aldosterone, and severe potassium depletion.

Vomiting is the classic, and it produces a recognisable picture: metabolic alkalosis with low chloride and low potassium.

And there is a self-perpetuating loop worth knowing. Volume depletion makes the kidney retain sodium avidly, and to do so it retains bicarbonate and excretes hydrogen. So the kidney maintains the alkalosis while trying to fix the volume. The alkalosis will not correct until the volume and chloride are replaced — which is why the treatment is saline, and why it is described as "chloride-responsive".

Reading a blood gas in four steps

This is a genuinely useful skill and it takes about twenty seconds.

Step 1 — look at the pH. Below 7.35 is acidaemia; above 7.45 is alkalaemia. If it is normal, there may still be two opposing disorders.

Step 2 — look at the CO₂. Does it explain the pH? High CO₂ with low pH means respiratory acidosis. Low CO₂ with high pH means respiratory alkalosis.

Step 3 — look at the bicarbonate. Does it explain the pH? Low bicarbonate with low pH means metabolic acidosis. High bicarbonate with high pH means metabolic alkalosis.

Step 4 — is the other value compensating? It should have moved in the same direction as the primary abnormality. If it has moved the opposite way, there are two disorders.

Then, if there is a metabolic acidosis, calculate the anion gap.

A worked example. pH 7.20, CO₂ 2.5 kPa (low), bicarbonate 8 mmol/L (low), sodium 140, chloride 100.

Step 1: acidaemia. Step 2: CO₂ is low, which would raise pH — so not the cause. Step 3: bicarbonate is low, which lowers pH — this is a metabolic acidosis. Step 4: the low CO₂ is respiratory compensation.

Anion gap: 140 − 100 − 8 = 32, markedly raised.

So: a raised anion gap metabolic acidosis with respiratory compensation. In a young person with a high glucose, that is diabetic ketoacidosis.

Two situations where this changes management

Aspirin overdose produces a mixed picture, and recognising it is diagnostic. Salicylate directly stimulates the respiratory centre, causing a respiratory alkalosis, and simultaneously uncouples oxidative phosphorylation (Chapter 1.6), causing a metabolic acidosis. A patient with both a low CO₂ and a low bicarbonate should raise the question immediately.

Treatment uses acid–base chemistry directly. Giving bicarbonate alkalinises the urine, which converts salicylate to its charged form — and charged molecules cannot cross membranes back into the tubule cells (Chapter 1.4). The drug is trapped in the urine and excreted. This is "ion trapping", and it is one of the neatest applications of basic chemistry in emergency medicine.

Chronic kidney disease causes a metabolic acidosis, because the kidney cannot excrete the daily acid load. Bone is used as a buffer, contributing to renal bone disease, and the acidosis also causes muscle wasting. Oral bicarbonate slows the progression of the kidney disease itself, which is a cheap and under-used intervention.

What the next page fixes

The kidney has made the urine. Chapter 10.5 covers what happens to it next — the bladder, the remarkably sophisticated reflex that fills and empties it, and why continence is a skill that has to be learned and can be lost.