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Compensation and mixed disorders

16 min

Skills you'll build3 skills
  • Calculate the Winters expected pCO₂ and compare it with the measured pCO₂
  • Calculate the expected bicarbonate for an acute or chronic respiratory disorder
  • Recognize a mixed disorder despite a near-normal pH

At the bench: Interpret a blood gas result with its specimen conditions

Try first

Try first

A primary metabolic acidosis shows bicarbonate 16 mmol/L and arterial pCO2 32 mm Hg. The Winters formula predicts pCO2 = 1.5 × bicarbonate + 8, ±2 mm Hg. What does the measured pCO2 show?

Keep going to see the reasoning.

Right. Keep going to follow the reasoning.

Keep going to see the reasoning.

Keep going to see the reasoning.

Get the idea

Use the explanation to check your first decision.

Expected compensation

Once the primary process is identified, the other variable is compared with the expected compensatory response. A value inside the expected range fits a single disorder. A value outside it points to a second primary process, an analytical problem, or a specimen from the wrong source.1 The rules are approximations, and published versions differ by small amounts.1

Respiratory compensation for metabolic disorders

The lungs adjust pCO2 within minutes. For metabolic acidosis, the Winters formula gives the expected value. In metabolic acidosis, expected arterial pCO₂ (mm Hg) = 1.5 × bicarbonate (mmol/L) + 8, with an expected range of ±2 mm Hg.2

A measured pCO2 above the range shows an added respiratory acidosis. A measured pCO2 below it shows an added respiratory alkalosis.1 In metabolic alkalosis, pCO2 rises about 0.7 mm Hg for each 1 mmol/L rise in bicarbonate above 24 mmol/L.1

Renal compensation for respiratory disorders

The kidneys need 3 to 5 days to reach their full response. The expected bicarbonate therefore depends on how long the pCO2 has been abnormal.1

Primary disorderBicarbonate change for each 10 mm Hg change in pCO2 from 40 mm Hg
Acute respiratory acidosisRises about 1 mmol/L
Chronic respiratory acidosisRises about 3.5 to 5 mmol/L
Acute respiratory alkalosisFalls about 2 mmol/L
Chronic respiratory alkalosisFalls about 4 to 5 mmol/L

The history and previous results show which row applies. Applying the chronic row to a sudden change predicts too much bicarbonate, and an appropriate bicarbonate is then misread as an added metabolic acidosis.1

Mixed disorders with a normal pH

Two primary processes that push pH in opposite directions can leave it inside 7.35 to 7.45. A low bicarbonate with a low pCO2 can be a metabolic acidosis with an added respiratory alkalosis. Comparison with the expected value detects it.1 Every gas gets the full check, including one with a pH within the reference interval.

Follow the bench demonstration

Sources for this step
References
  1. Rifai N, Chiu RWK, Young I, Burnham CAD, Wittwer CT, eds. Tietz Textbook of Laboratory Medicine. 7th ed. Elsevier; 2023.
  2. Albert MS, Dell RB, Winters RW. Quantitative displacement of acid-base equilibrium in metabolic acidosis. Ann Intern Med. 1967;66(2):312-322. doi:10.7326/0003-4819-66-2-312

Watch one

Read each decision and its explanation.

An arterial gas shows a primary metabolic acidosis: pH 7.14, bicarbonate 10 mmol/L and pCO2 30 mm Hg. The specimen source and handling are confirmed. Is the respiratory response what the Winters formula expects?

  1. Confirm the primary process: the low pH and low bicarbonate show metabolic acidosis.

    The formula applies only once metabolic acidosis is the primary process.

  2. Calculate: 1.5 × 10 mmol/L + 8 = 23 mm Hg.

    The expected pCO₂ comes from the measured bicarbonate.

  3. Set the range: 21 to 25 mm Hg.

    The formula has a range of ±2 mm Hg.

  4. Compare: the measured 30 mm Hg is 5 mm Hg above the top of the range.

    A measured value above the range means ventilation is not removing CO₂ as expected.

  5. Interpret it. The pCO2 shows an added respiratory acidosis.

    A second process is identified only after the comparison.

Expected pCO2 is 23 mm Hg (21 to 25 mm Hg). The measured 30 mm Hg is above it, so the gas shows metabolic acidosis with an added respiratory acidosis.

Practice this skill

Your turn

Problem 1 of 3 · Hints available

Metabolic acidosis is established, with HCO₃⁻ 12 mmol/L and arterial pCO₂ 36 mm Hg. Using Winters formula, what does the respiratory component suggest?

Incorrect. Winters formula predicts 1.5 × 12 + 8 = 26 ± 2 mm Hg. The measured 36 is above that range.

Incorrect. An additional respiratory alkalosis would lower pCO₂ below the expected range of 24–28 mm Hg.

Correct. Expected pCO₂ is 24–28 mm Hg. A measured 36 is higher, supporting additional respiratory acidosis after specimen and analytical validity are checked.

Hint
  1. Calculate 1.5 × bicarbonate + 8 first.
  2. Add and subtract 2 mm Hg to get the range.
  3. Ask what a pCO2 higher than the range shows about ventilation.

Review Systematic interpretation

Problem 2 of 3 · Hints available

A patient with no lung disease has respiratory depression after an opioid overdose. An arterial gas an hour later gives pCO2 70 mm Hg and bicarbonate 27 mmol/L. How do you interpret the bicarbonate?

pCO2 rose 30 mm Hg within an hour. The acute rule predicts a bicarbonate rise of about 3 mmol/L, to about 27 mmol/L, which is what was measured.

The chronic rule predicts 34.5 to 39 mmol/L. The kidneys have had one hour, so the acute rule applies, and it predicts about 27 mmol/L.

Applied the chronic rule to an acute pCO₂ change

Renal compensation takes hours to days, so in acute respiratory acidosis buffering raises bicarbonate only about 1 mmol/L per 10 mm Hg pCO₂. In chronic respiratory acidosis it rises 3.5 to 5 mmol/L per 10 mm Hg. Using the chronic expectation for an acute change predicts too large a bicarbonate response and can label an appropriate result as an added metabolic process.

The acute rule predicts a rise of about 3 mmol/L from 24 mmol/L. A bicarbonate of 27 mmol/L matches it.

Hint
  1. Decide first whether this change is acute or chronic.
  2. Count how many 10 mm Hg steps pCO2 has risen above 40 mm Hg.

Review The four primary acid-base disorders

Problem 3 of 3 · On your own

An arterial gas gives pH 7.41, bicarbonate 15 mmol/L and pCO2 24 mm Hg. The specimen source and handling are confirmed. What does the gas show?

A bicarbonate of 15 mmol/L shows a metabolic acidosis. The Winters range is 28.5 to 32.5 mm Hg, and a pCO2 of 24 mm Hg below it shows a second process that keeps the pH near 7.40.

Stopped because pH was within the reference interval

Opposing primary processes can leave pH near normal. With pH 7.42, bicarbonate 14 mmol/L, and pCO₂ 22 mm Hg, the expected pCO₂ is 29 ±2 mm Hg, so the lower measured value shows an added respiratory alkalosis that a pH-only reading misses.

The Winters formula gives 1.5 × 15 + 8 = 30.5 mm Hg, with a range of 28.5 to 32.5 mm Hg. The measured 24 mm Hg is below it.

An added respiratory acidosis would raise pCO2 above 32.5 mm Hg. This pCO2 is lower than the range.

The expected pCO2 is 28.5 to 32.5 mm Hg. The measured 24 mm Hg is lower, so an added respiratory alkalosis is present, and the two processes leave the pH near 7.40.

Review Systematic interpretation

Use it

Read the case evidence, then make each decision. The step is complete without it.

  • Marguerite Smeaton, 74, MRN 4417360, has long-standing lung disease with chronic CO2 retention.
  • She started a new diuretic 2 weeks ago.
  • An arterial gas is drawn on 2 L/min of oxygen by nasal cannula, recorded on the requisition.
  • The syringe has no air and a correct fill, and QC for the run is acceptable.
TestResultPreviousReference intervalFlag
pH7.455 weeks ago: 7.357.355 weeks ago7.35–7.457.35–7.45
pCO261 mm Hg High5 weeks ago: 58 mm Hg58 mm Hg5 weeks ago35–45 mm Hg35–45High
Bicarbonate41 mmol/L High5 weeks ago: 32 mmol/L32 mmol/L5 weeks ago22–28 mmol/L22–28High

Specimen: Not measured on this analyzer. Arterial, 2 L/min oxygen by nasal cannula

Decision 1 of 2

Which expected bicarbonate fits her pCO2 of 61 mm Hg?

Her pCO2 has been high for weeks, as the previous result shows. The kidneys have had time for their full response, so the chronic rule applies.

pCO2 is 21 mm Hg above 40 mm Hg. The chronic rule adds 3.5 to 5 mmol/L for each 10 mm Hg, so about 7 to 10 mmol/L above 24 mmol/L.

The expected value comes from the pCO2 and the rule. The measured value is then compared with it.

Review The four primary acid-base disorders

Decision 2 of 2

The pH is 7.45, at the top of the reference interval. What does the bicarbonate of 41 mmol/L show?

The bicarbonate is 7 mmol/L above the chronic range, and it rose from 32 mmol/L after the new diuretic. An added metabolic alkalosis explains both the extra bicarbonate and the pH near 7.45.

Compensation alone predicts 31 to 34 mmol/L, and her own result 5 weeks ago was 32 mmol/L. A bicarbonate of 41 mmol/L is well above that, and the pH near the top of the interval masks the second process.

Stopped because pH was within the reference interval

Opposing primary processes can leave pH near normal. With pH 7.42, bicarbonate 14 mmol/L, and pCO₂ 22 mm Hg, the expected pCO₂ is 29 ±2 mm Hg, so the lower measured value shows an added respiratory alkalosis that a pH-only reading misses.

Two processes that push pH in opposite directions can leave it within the interval. The specimen and the run are acceptable here.

Review Systematic interpretation

Her bicarbonate of 41 mmol/L is well above the expected range. The chronic rule predicts 31 to 34 mmol/L, and her own baseline was 32 mmol/L. The extra bicarbonate shows an added metabolic alkalosis, which the pH alone would not reveal.

For reference

Sources checked