Physiology chapters
Acid-base balance and disturbances
How the body keeps blood pH near 7.4 through buffers, the lungs and the kidneys, the four primary acid-base disturbances with their causes and compensation, and a simple way to read a blood gas.
- Normal arterial pH is 7.35–7.45, PCO2 35–45 mmHg and HCO3− 22–26 mmol/L; pH depends on the ratio of HCO3− to CO2 (Henderson-Hasselbalch).
- Three lines of defence: buffers (seconds), lungs (minutes, change CO2) and kidneys (hours to days, change HCO3− and excrete H+).
- Respiratory disorders change PCO2 first; metabolic disorders change HCO3− first; the other system compensates in the same direction.
On this page
Overview
The body makes acid all the time, from metabolism (CO2, and fixed acids such as sulphuric and lactic acid). Yet blood pH stays within a narrow range, about 7.35–7.45, because enzymes and organs work properly only in this range.
Three systems protect pH:
- Chemical buffers: act within seconds.
- The lungs: adjust CO2 within minutes.
- The kidneys: adjust bicarbonate and excrete acid over hours to days; the most powerful.
Normal values (arterial blood)
| Measure | Normal range |
|---|---|
| pH | 7.35–7.45 |
| PCO2 | 35–45 mmHg (4.7–6.0 kPa) |
| HCO3− | 22–26 mmol/L |
pH below 7.35 is acidaemia; above 7.45 is alkalaemia.
Buffers
A buffer is a weak acid and its base that soak up added H+ or OH− with little change in pH.
The bicarbonate buffer
CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3−
Henderson-Hasselbalch equation:
pH = 6.1 + log (HCO3− ÷ 0.03 × PCO2)
With normal values: 6.1 + log (24 ÷ 1.2) = 6.1 + log 20 = 7.4.
The pH depends on the ratio of bicarbonate to CO2 (normally 20 : 1), not on either value alone.
The bicarbonate system is the most important ECF buffer, even though its pK (6.1) is far from 7.4, because both parts are controlled: CO2 by the lungs and HCO3− by the kidneys.
Other buffers
- Phosphate buffer: important inside cells and in the tubular fluid (pK about 6.8, close to body pH).
- Proteins: the most plentiful buffers inside cells; haemoglobin is a major buffer in blood.
Respiratory control
A rise in H+ or CO2 stimulates breathing, which blows off CO2 and raises pH. A fall does the opposite. This is fast but cannot fully correct a metabolic problem, because the stimulus fades as pH improves.
Renal control
The kidneys:
- Reabsorb almost all filtered bicarbonate (mostly in the proximal tubule).
- Secrete H+ (proximal tubule by Na+/H+ exchange; intercalated cells by H+-ATPase).
- Make new bicarbonate for each H+ excreted.
Secreted H+ is excreted bound to buffers, because urine pH cannot fall much below 4.5:
- Titratable acid: H+ bound mainly to phosphate (HPO4²− → H2PO4−).
- Ammonium (NH4+): ammonia made from glutamine in tubular cells combines with H+. Ammonia production increases greatly in chronic acidosis, so it is the main adaptive route.
The kidneys excrete acid as titratable acid and ammonium; increased ammonia production is the main response to chronic acidosis.
The four primary disturbances
| Disorder | Primary change | pH | Compensation |
|---|---|---|---|
| Respiratory acidosis | ↑ PCO2 | ↓ | Kidneys raise HCO3− (days) |
| Respiratory alkalosis | ↓ PCO2 | ↑ | Kidneys lower HCO3− |
| Metabolic acidosis | ↓ HCO3− | ↓ | Lungs lower PCO2 (hyperventilation) |
| Metabolic alkalosis | ↑ HCO3− | ↑ | Lungs raise PCO2 (hypoventilation, limited) |
In compensation, the second value moves in the same direction as the first (both up or both down), and compensation does not overcorrect the pH.
Respiratory acidosis
Causes: hypoventilation: COPD, severe asthma, opioid or sedative overdose, neuromuscular weakness (Guillain-Barré, myasthenia), chest wall disease, airway obstruction.
Respiratory alkalosis
Causes: hyperventilation: anxiety, pain, high altitude, early salicylate poisoning, pulmonary embolism, fever, liver failure, pregnancy, over-ventilation on a ventilator.
Low CO2 reduces ionised calcium, causing tingling and tetany.
Metabolic acidosis
Causes are grouped by the anion gap:
Anion gap = Na+ − (Cl− + HCO3−); normal about 8–16 mmol/L (lab ranges vary).
| Raised anion gap (an extra acid is added) | Normal anion gap (bicarbonate lost; chloride rises) |
|---|---|
| Diabetic ketoacidosis | Diarrhoea |
| Lactic acidosis (shock, sepsis, hypoxia) | Renal tubular acidosis |
| Kidney failure (retained acids) | Acetazolamide |
| Poisoning: methanol, ethylene glycol, salicylates | Ureteric diversion into bowel |
The body compensates with deep, rapid breathing (Kussmaul breathing).
Metabolic alkalosis
Causes:
- Vomiting or nasogastric suction: loss of HCl.
- Diuretics (loop and thiazide).
- Hyperaldosteronism, Cushing's syndrome.
- Too much bicarbonate or antacid.
Volume depletion and low potassium keep the kidneys reabsorbing bicarbonate and sustain the alkalosis.
Vomiting → hypochloraemic, hypokalaemic metabolic alkalosis. Diarrhoea → normal anion gap metabolic acidosis.
A simple way to read a blood gas
- pH: acidaemia or alkalaemia?
- PCO2: does it explain the pH? (High PCO2 with low pH = respiratory acidosis.)
- HCO3−: does it explain the pH? (Low HCO3− with low pH = metabolic acidosis.)
- Compensation: is the other value moving the same way?
- In metabolic acidosis, calculate the anion gap.
Example: pH 7.25, PCO2 28 mmHg, HCO3− 12 mmol/L. Low pH; HCO3− low explains it: metabolic acidosis; PCO2 low: respiratory compensation.
Effect on potassium
In acidosis, H+ moves into cells in exchange for K+, so plasma K+ tends to rise. In alkalosis, plasma K+ tends to fall.
Expect: normal values, the Henderson-Hasselbalch equation and the 20 : 1 ratio, why bicarbonate is the most important ECF buffer, how kidneys excrete acid (titratable acid and ammonium), the four primary disorders with causes and compensation, the anion gap, and the acid-base results of vomiting and diarrhoea.
Quick revision
- pH 7.35–7.45; PCO2 35–45; HCO3− 22–26.
- pH = 6.1 + log (HCO3− ÷ 0.03 PCO2); normal ratio 20 : 1.
- Buffers: bicarbonate (ECF), phosphate (cells and urine), proteins (Hb).
- Kidneys: reclaim HCO3−, secrete H+, excrete titratable acid and NH4+.
- Compensation moves the other value the same way; no overcorrection.
- Vomiting: metabolic alkalosis. Diarrhoea: normal-gap metabolic acidosis.
- DKA, lactic acidosis, renal failure, poisons: high anion gap.
Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).
FAQ
What is the most important buffer in extracellular fluid?
The bicarbonate buffer system, because both CO2 and bicarbonate can be adjusted by the lungs and kidneys.
How do the kidneys compensate for respiratory acidosis?
They excrete more H+ and make and reabsorb more bicarbonate over several days, raising plasma HCO3−.
What acid-base disorder does vomiting cause?
Metabolic alkalosis, with low chloride and low potassium.
What is the anion gap?
Sodium minus the sum of chloride and bicarbonate; it rises when an unmeasured acid such as ketones or lactate is added.