Fluid, Electrolyte and Acid-Base Balance

Every cell in the body lives in a chemical bath whose composition it does not control but on which its survival absolutely depends. The kidneys, lungs, and a handful of hormones work minute by minute to keep that bath within extraordinarily tight limits — the sodium concentration varies by only a few percent in health, and the blood pH swings across a range narrower than a single unit is wide. When that regulation fails, the consequences are fast and dramatic: seizures, cardiac arrest, coma. This is why fluid, electrolyte, and acid-base disturbances are among the most common problems on any hospital ward and among the highest-yield topics in medicine.

The good news is that this subject rewards a systematic mind. Once you understand the few underlying principles — where water goes, how the kidney handles sodium and potassium, and how the body defends its pH — the bedside chaos of numbers resolves into a small number of recognisable patterns. This page teaches you those principles and gives you a reliable, repeatable method for interpreting an arterial blood gas (ABG).

Learning Objectives

• Explain how body water is distributed and what determines serum sodium concentration
• Classify and work up hyponatraemia and hypernatraemia by volume status and tonicity
• Recognise the causes, ECG changes, and emergency management of hyper- and hypokalaemia
• Describe the three lines of pH defence: chemical buffers, the lungs, and the kidneys
• Derive and apply the Henderson-Hasselbalch equation and the bicarbonate buffer system
• Interpret an ABG step by step, including the anion gap and expected compensation
• Distinguish primary from compensatory acid-base changes and identify mixed disorders

Quick Answer

Serum sodium reflects water balance, not salt content — hyponatraemia usually means too much water relative to solute, and its workup hinges on serum osmolality and volume status. Potassium is mostly intracellular, so serum values are influenced by shifts (acidosis, insulin) as well as total-body balance; both extremes are life-threatening through cardiac arrhythmia. Acid-base balance is defended by rapid chemical buffers (chiefly bicarbonate), the lungs (adjusting CO2 in minutes), and the kidneys (adjusting bicarbonate and acid excretion over hours to days). The Henderson-Hasselbalch equation links pH to the ratio of bicarbonate to dissolved CO2. To read an ABG, check the pH (acidaemic or alkalaemic), decide whether the CO2 or bicarbonate explains it, calculate the anion gap for any metabolic acidosis, and confirm compensation is appropriate — inappropriate compensation reveals a mixed disorder.

Where It Came From

For most of medical history, the idea that blood had a measurable "acidity" was unimaginable — pH itself did not exist as a concept until the 20th century. The story begins in 1908 when the American physiologist Lawrence J. Henderson, studying how the body neutralises the acids produced by metabolism, wrote out the mass-action relationship for the bicarbonate–carbonic acid system. He showed that hydrogen ion concentration depended on the ratio of carbonic acid to bicarbonate, not the absolute amount of either — a profound insight, because it explained how the body could hold acidity steady while dumping large quantities of acid.

The motivation was intensely practical. Physiologists knew that muscles and tissues generate a torrent of acid every day — carbon dioxide from respiration, lactic and other organic acids from metabolism — yet blood pH barely moves. How? The answer had to be a buffer: a chemical pair that absorbs added acid or base with minimal change in pH. Henderson identified bicarbonate as the master buffer of blood.

The equation took its familiar logarithmic form after the Danish chemist Søren Sørensen introduced the pH scale in 1909, and Karl Albert Hasselbalch, another Dane, recast Henderson's relationship using logarithms in 1916 — giving us the Henderson-Hasselbalch equation. The clinical payoff came decades later. During the 1952 Copenhagen polio epidemic, patients were dying of respiratory failure, and the anaesthetist Bjørn Ibsen realised many deaths were from CO2 retention (respiratory acidosis), not oxygen lack. Manual ventilation saved lives and launched both intensive care medicine and the routine measurement of blood gases. The electrode-based blood gas analyser, developed through the 1950s and 60s, finally put Henderson's abstraction into the hands of every clinician.

Body Water, Osmolality, and Sodium

Total body water is roughly 60% of body weight, split two-thirds intracellular and one-third extracellular; the extracellular compartment is further divided into interstitial fluid and plasma. Water moves freely across cell membranes and distributes to equalise osmolality (solute concentration) everywhere. Sodium is the dominant extracellular solute, so it is the main determinant of how water partitions — but crucially, the serum sodium concentration tells you about water, not about how much sodium is in the body.

A worked way to see this: pour a litre of pure water into the blood and the sodium concentration falls even though not one sodium ion was lost. Conversely, lose water through fever and sweating and sodium rises. This is why hyponatraemia is fundamentally a water problem.

Approach to Hyponatraemia

Step one is measured serum osmolality, to exclude pseudohyponatraemia (severe hyperlipidaemia or paraproteinaemia) and hyperosmolar causes (severe hyperglycaemia, where glucose draws water out of cells and dilutes sodium — correct the measured sodium up by about 2.4 mmol/L for every 5.5 mmol/L glucose above normal).

For true hypo-osmolar hyponatraemia, assess volume status:

• Hypovolaemic: sodium and water both lost, water partially replaced (diarrhoea, vomiting, diuretics, adrenal insufficiency). Urine sodium is low if losses are non-renal.
• Euvolaemic: SIADH is the classic cause — inappropriate ADH keeps water despite low osmolality; urine is inappropriately concentrated with high urine sodium. Also hypothyroidism and glucocorticoid deficiency.
• Hypervolaemic: total-body sodium excess but even greater water excess — heart failure, cirrhosis, nephrotic syndrome.

The danger in correction is speed, not just endpoint. Raising sodium faster than about 8–10 mmol/L in 24 hours risks osmotic demyelination syndrome (central pontine myelinolysis), a devastating and often irreversible brainstem injury. Chronic hyponatraemia must always be corrected slowly.

Potassium: The Intracellular Cation

About 98% of body potassium is inside cells; the tiny extracellular fraction sets the resting membrane potential of excitable tissue, which is why both hyper- and hypokalaemia threaten the heart. Serum potassium reflects two things: total-body balance (intake versus renal/gut loss) and transcellular shifts. Insulin, beta-2 agonists, and alkalosis drive potassium into cells; acidosis, cell lysis, and insulin deficiency drive it out. This is the key to emergency management — you can lower a dangerous serum potassium in minutes by shifting it, while you arrange to actually remove it.

Hyperkalaemia

Causes include renal failure, potassium-sparing drugs (ACE inhibitors, spironolactone), acidosis, and massive tissue breakdown (rhabdomyolysis, tumour lysis, haemolysis). ECG evolves through peaked T waves, then flattened P waves and widened QRS, finally a sine-wave pattern and arrest.

Emergency management, step by step:

1. Stabilise the myocardium: IV calcium gluconate — does not lower potassium but antagonises its cardiac effect within minutes.
2. Shift potassium into cells: IV insulin with dextrose (to prevent hypoglycaemia), and nebulised salbutamol.
3. Remove potassium: loop diuretics if the patient makes urine, gut binders, and dialysis for refractory or renal-failure cases.

Hypokalaemia

Causes include diuretics, vomiting and diarrhoea, and hyperaldosteronism. ECG shows flattened T waves, ST depression, and U waves, with risk of arrhythmia. Replace potassium, correct magnesium (low magnesium makes potassium irreplaceable because it promotes renal potassium wasting), and treat the cause.

Acid-Base Balance and the Three Defences

The body produces around 15,000 mmol of CO2 (volatile acid) and 50–100 mmol of fixed acid daily, yet keeps arterial pH at 7.35–7.45. It does this in three tiers of increasing capacity but decreasing speed.

1. Chemical buffers (seconds). The dominant one is bicarbonate. The reaction

$\text{CO}_2 + \text{H}_2\text{O} \leftrightarrow \text{H}_2\text{CO}_3 \leftrightarrow \text{H}^+ + \text{HCO}_3^-$

is the engine of pH control. Its power lies in being open: the lungs can blow off CO2 and the kidneys can regenerate bicarbonate, so the buffer never gets used up. The Henderson-Hasselbalch equation describes it:

pH = 6.1 + log ( bicarbonate / (0.03 times pCO2) )

Read this qualitatively for exams: pH tracks the ratio of bicarbonate (a metabolic, kidney-controlled term) to pCO2 (a respiratory, lung-controlled term). Raise bicarbonate or lower CO2 and pH rises; the opposite lowers it.

2. Respiratory compensation (minutes). Chemoreceptors sense pH and CO2; in a metabolic acidosis the patient hyperventilates (Kussmaul breathing) to blow off CO2 and pull the ratio back up.

3. Renal compensation (hours to days). The kidney reclaims filtered bicarbonate, generates new bicarbonate, and excretes acid buffered by ammonium and phosphate. It is slow but has enormous capacity, and it is the definitive defence against chronic acid loads.

Interpreting an Arterial Blood Gas: A Reliable Method

Work through these steps in the same order every time.

Step 1 — Look at the pH. Below 7.35 is acidaemia; above 7.45 is alkalaemia. Even if compensation has pulled pH toward normal, whichever side of 7.40 it sits usually reveals the primary process.

Step 2 — Identify the primary driver. Check pCO2 (normal about 35–45 mmHg) and bicarbonate (about 22–26 mmol/L).

• Acidaemia with high pCO2 = respiratory acidosis. With low bicarbonate = metabolic acidosis.
• Alkalaemia with low pCO2 = respiratory alkalosis. With high bicarbonate = metabolic alkalosis.

Step 3 — For metabolic acidosis, calculate the anion gap.

Anion gap = Na minus (Cl plus bicarbonate); normal is about 8–12 mmol/L (correct for low albumin — add ~2.5 per 10 g/L fall).

• High anion gap (mnemonic GOLD MARK: Glycols, Oxoproline, L-lactate, D-lactate, Methanol, Aspirin, Renal failure, Ketoacidosis) — unmeasured acids are present.
• Normal anion gap (hyperchloraemic) — bicarbonate lost through gut (diarrhoea) or kidney (renal tubular acidosis).

Step 4 — Check compensation is appropriate. Use a rule such as Winter's formula for metabolic acidosis: expected pCO2 = (1.5 times bicarbonate) + 8, plus or minus 2. If the measured pCO2 sits outside the expected range, a second, independent disorder is present (a mixed disorder). Remember: compensation never fully normalises the pH and never overshoots.

Worked Example

A young patient with diabetes presents drowsy and breathing deeply. ABG: pH 7.12, pCO2 20 mmHg, bicarbonate 6 mmol/L, Na 138, Cl 100.

• Step 1: pH 7.12 = acidaemia.
• Step 2: bicarbonate is very low → metabolic acidosis.
• Step 3: anion gap = 138 − (100 + 6) = 32 → high anion gap.
• Step 4: Winter's expected pCO2 = (1.5 × 6) + 8 = 17 ± 2, so 15–19. Measured is 20 — essentially appropriate respiratory compensation.

Diagnosis: high-anion-gap metabolic acidosis with appropriate respiratory compensation — diabetic ketoacidosis. Treat with fluids, insulin, and careful potassium replacement.

Real-World Applications

• Diabetic ketoacidosis: the ABG guides diagnosis and the potassium value dictates whether you can start insulin (insulin drives potassium into cells and can precipitate fatal hypokalaemia).
• The vomiting patient: loss of gastric acid produces a hypochloraemic, hypokalaemic metabolic alkalosis — the classic pattern in pyloric stenosis.
• The breathless patient: a rising pCO2 in COPD signals type 2 respiratory failure and the need for ventilatory support, exactly the lesson of the 1952 Copenhagen epidemic.
• Hospital fluid prescribing: understanding tonicity prevents the iatrogenic hyponatraemia that once killed children given hypotonic maintenance fluids.

Common Mistakes

1. Treating hyponatraemia as a salt-deficiency problem. It is almost always a water-handling problem; giving salt without addressing water balance and correcting too fast can cause osmotic demyelination. The correction is to classify by osmolality and volume status and correct slowly.
2. Chasing a normal pH and declaring the patient fine. A near-normal pH with grossly abnormal pCO2 and bicarbonate usually means either a well-compensated disorder or two opposing disorders. Always inspect the individual components and check compensation with a formula.
3. Forgetting to correct the anion gap for albumin. In a hypoalbuminaemic patient a "normal" gap may hide a significant high-gap acidosis. Add roughly 2.5 mmol/L to the gap for every 10 g/L the albumin falls below normal.

Comparison and Connections

Feature	Respiratory	Metabolic
Primary abnormality	pCO2	Bicarbonate
Controlled by	Lungs	Kidneys
Speed of change	Minutes	Hours to days
Compensation organ	Kidney (slow)	Lung (fast)

Disorder	pH	Primary change	Compensation
Metabolic acidosis	Low	Low bicarbonate	Low pCO2
Metabolic alkalosis	High	High bicarbonate	High pCO2
Respiratory acidosis	Low	High pCO2	High bicarbonate
Respiratory alkalosis	High	Low pCO2	Low bicarbonate

Sodium and potassium disorders connect closely to acid-base: acidosis shifts potassium out of cells, and hyperaldosteronism causes both hypokalaemia and metabolic alkalosis. For the underlying regulatory hormones see renal physiology and endocrinology.

Practice Questions

Recall

What are the normal reference ranges for arterial pH, pCO2, and bicarbonate?

Answer: pH 7.35–7.45; pCO2 35–45 mmHg; bicarbonate 22–26 mmol/L.

Understanding

Why does serum sodium concentration reflect water balance rather than total-body sodium?

Answer: Water moves freely to equalise osmolality, and sodium is the main extracellular solute. Adding or losing water dilutes or concentrates sodium without changing the total amount of sodium in the body, so the concentration is really a measure of the water-to-solute ratio.

Application

A patient with severe diarrhoea has pH 7.28, pCO2 32, bicarbonate 15, Na 140, Cl 115. What is the disturbance?

Answer: Acidaemia with low bicarbonate = metabolic acidosis. Anion gap = 140 − (115 + 15) = 10 (normal). A normal-gap acidosis from gastrointestinal bicarbonate loss, with appropriate respiratory compensation.

Analysis

An ABG shows pH 7.39, pCO2 60, bicarbonate 35. Explain why this is not simply well-compensated respiratory acidosis, and what a normal pH here should prompt.

Answer: Compensation never fully normalises pH, and a pH of 7.39 with both a high pCO2 and a high bicarbonate suggests a mixed picture — for example a chronic respiratory acidosis plus a coexisting metabolic alkalosis (perhaps from diuretics or vomiting). Apply the expected-compensation rule for chronic respiratory acidosis; if bicarbonate exceeds the predicted rise, a second, metabolic alkalotic process is present.

FAQ

Why do I need arterial rather than venous blood for a gas? Arterial samples give an accurate pO2 for assessing oxygenation. For pH, pCO2, and bicarbonate, venous values correlate closely enough that a venous gas is often used to screen acid-base status, but oxygenation needs arterial or pulse oximetry.

How can the pH be normal when the patient is clearly sick? Compensation can pull the pH back toward the reference range, and two opposing primary disorders can cancel each other out on the pH while both distorting the components. Always read pCO2 and bicarbonate, not just pH.

Why do we give calcium in hyperkalaemia if it doesn't lower potassium? Calcium raises the threshold potential of cardiac cells, restoring the normal gap between resting and threshold voltage and stabilising the myocardium against arrhythmia. It buys time while insulin, salbutamol, and definitive removal take effect.

What actually is the anion gap measuring? It estimates unmeasured anions in plasma. Because the lab does not measure every anion (e.g. lactate, ketoacids, sulphate), a rise in these acids shows up as a widened gap, pointing you toward specific causes of metabolic acidosis.

Why must I check magnesium when potassium won't come up? Low magnesium promotes renal potassium wasting and impairs potassium uptake into cells. Until magnesium is replaced, supplemented potassium is lost in the urine, so refractory hypokalaemia is often really unrecognised hypomagnesaemia.

Quick Revision

• Serum sodium = a water problem; classify hyponatraemia by osmolality then volume status; correct chronic cases slowly to avoid osmotic demyelination.
• Potassium is mainly intracellular; acidosis and cell lysis raise it, insulin and alkalosis lower it; both extremes kill via arrhythmia.
• Hyperkalaemia emergency: stabilise (calcium), shift (insulin/dextrose, salbutamol), remove (diuretics, dialysis).
• pH is defended by buffers (seconds), lungs (minutes), kidneys (days); bicarbonate is the master open buffer.
• Henderson-Hasselbalch: pH tracks the ratio of bicarbonate to pCO2.
• ABG steps: pH → primary driver (pCO2 vs bicarbonate) → anion gap for metabolic acidosis → check compensation (Winter's formula) for mixed disorders.
• Anion gap = Na − (Cl + bicarbonate); correct for low albumin.

Related Topics

Prerequisites

• Nephrology overview
• Renal physiology and tubular transport (see ../../2._Physiology/index.md)

Related Topics

• Acute kidney injury and chronic kidney disease (see the Nephrology branch overview: ../index.md)
• Endocrine control of salt and water: aldosterone and ADH (see ../../27._Endocrinology/index.md)

Next Topics

• Diuretics and their electrolyte effects (see ../../5._Pharmacology/index.md)
• Acute and chronic kidney disease management (../index.md)