A 65-year-old man is brought to the emergency department from his home. He is unresponsive. His son requested a wellness check because he had not heard from his father in 2 weeks. He reports that his father was sounding depressed during a telephone call. The paramedics found a suicide note and a half-empty bottle of antifreeze near the patient. The medical history includes hypertension and hyperlipidemia. The vital signs include: blood pressure 120/80 mm Hg, respiratory rate 25/min, heart rate 95/min, and temperature 37.0°C (98.5°F). He is admitted to the hospital. What do you expect the blood gas analysis to show?

Non-anion gap metabolic acidosis

A 32-year-old man is brought to the emergency department after he was found unresponsive on the street. Upon admission, he is lethargic and cyanotic with small, symmetrical pinpoint pupils. The following vital signs were registered: blood pressure of 100/60 mm Hg, heart rate of 70/min, respiratory rate of 8/min, and a body temperature of 36.0°C (96.8°F). While being assessed and resuscitated, a sample for arterial blood gas (ABG) analysis was taken, in addition to the following biochemistry tests: Laboratory test Serum Na+ 138 mEq/L Serum Cl- 101 mEq/L Serum K+ 4.0 mEq/L Serum creatinine (SCr) 0.58 mg/dL Which of the following values would you most likely expect to see in this patient’s ABG results?

pH: decreased, HCO3- : increased, Pco2: increased

pH: increased, HCO3- : decreased, Pco2: decreased

pH: decreased, HCO3- : decreased, Pco2: decreased

pH: increased, HCO3- : increased, Pco2: increased

pH: normal, HCO3- : increased, Pco2: increased

A 58-year-old man presents to the emergency department with a chief complaint of ringing in his ears that started several hours previously that has progressed to confusion. The patient denies any history of medical problems except for bilateral knee arthritis. He was recently seen by an orthopedic surgeon to evaluate his bilateral knee arthritis but has opted to not undergo knee replacement and prefers medical management. His wife noted that prior to them going on a hike today, he seemed confused and not himself. They decided to stay home, and roughly 14 hours later, he was no longer making any sense. Physical exam is notable for a confused man. The patient's vitals are being performed and his labs are being drawn. Which of the following is most likely to be seen on blood gas analysis?

pH: 7.30, PaCO2: 15 mmHg, HCO3-: 16 mEq/L

pH: 7.37, PaCO2: 41 mmHg, HCO3-: 12 mEq/L

pH: 7.41, PaCO2: 65 mmHg, HCO3-: 34 mEq/L

pH: 7.47, PaCO2: 11 mmHg, HCO3-: 24 mEq/L

pH: 7.31, PaCO2: 31 mmHg, HCO3-: 15 mEq/L

A 75-year-old woman with late-onset autoimmune diabetes mellitus, rheumatoid arthritis, coronary artery disease, and idiopathic pulmonary fibrosis presents to the ship medic with altered mental status. While on her current cruise to the Caribbean islands, she experienced nausea, vomiting, and diarrhea. She takes aspirin, simvastatin, low-dose prednisone, glargine, and aspart. She is allergic to amoxicillin and shellfish. She works as a greeter at a warehouse and smokes 5 packs/day. Her temperature is 100.5°F (38.1°C), blood pressure is 90/55 mmHg, pulse is 130/min, and respirations are 30/min. Her pupils are equal and reactive to light bilaterally. Her lungs are clear to auscultation bilaterally, but her breath has a fruity odor. She has an early systolic murmur best appreciated at the left upper sternal border. She has reproducible peri-umbilical tenderness. Which of the following will most likely be present in this patient?

Respiratory alkalosis and anion-gap metabolic acidosis

Respiratory acidosis and anion-gap metabolic acidosis

Respiratory alkalosis and non anion-gap metabolic acidosis

Respiratory acidosis and contraction metabolic alkalosis

Respiratory alkalosis and non-contraction metabolic alkalosis

A 52-year-old man with a history of Type 1 diabetes mellitus presents to the emergency room with increasing fatigue. Two days ago, he ran out of insulin and has not had time to obtain a new prescription. He denies fevers or chills. His temperature is 37.2 degrees Celsius, blood pressure 84/56 mmHg, heart rate 100/min, respiratory rate 20/min, and SpO2 97% on room air. His physical exam is otherwise within normal limits. An arterial blood gas analysis shows the following: pH 7.25, PCO2 29, PO2 95, HCO3- 15. Which of the following acid-base disorders is present?

Metabolic acidosis with appropriate respiratory compensation

Respiratory alkalosis with appropriate metabolic compensation

Respiratory acidosis with appropriate metabolic compensation

Mixed metabolic and respiratory acidosis

Metabolic alkalosis with appropriate respiratory compensation

A 72-year-old man being treated for benign prostatic hyperplasia (BPH) is admitted to the emergency department for 1 week of dysuria, nocturia, urge incontinence, and difficulty initiating micturition. His medical history is relevant for hypertension, active tobacco use, chronic obstructive pulmonary disease, and BPH with multiple urinary tract infections. Upon admission, he is found with a heart rate of 130/min, respiratory rate of 19/min, body temperature of 39.0°C (102.2°F), and blood pressure of 80/50 mm Hg. Additional findings during the physical examination include decreased breath sounds, wheezes, crackles at the lung bases, and intense right flank pain. A complete blood count shows leukocytosis and neutrophilia with a left shift. A sample for arterial blood gas analysis (ABG) was taken, which is shown below. Laboratory test Serum Na+ 140 mEq/L Serum Cl- 102 mEq/L Serum K+ 4.8 mEq/L Serum creatinine (SCr) 2.3 mg/dL Arterial blood gas pH 7.12 Po2 82 mm Hg Pco2 60 mm Hg SO2% 92% HCO3- 12.0 mEq/L Which of the following best explains the patient’s condition?

Metabolic acidosis complicated by respiratory acidosis

Metabolic acidosis complicated by respiratory alkalosis

Non-anion gap metabolic acidosis

Respiratory alkalosis complicated by metabolic acidosis

Respiratory acidosis complicated by metabolic alkalosis

A 54-year-old man presents with 3 days of non-bloody and non-bilious emesis every time he eats or drinks. He has become progressively weaker and the emesis has not improved. He denies diarrhea, fever, or chills and thinks his symptoms may be related to a recent event that involved sampling many different foods. His temperature is 97.5°F (36.4°C), blood pressure is 133/82 mmHg, pulse is 105/min, respirations are 15/min, and oxygen saturation is 98% on room air. Physical exam is notable for a weak appearing man with dry mucous membranes. His abdomen is nontender. Which of the following laboratory changes would most likely be seen in this patient?

Metabolic alkalosis and hypokalemia

Metabolic alkalosis and hyperkalemia

Non-anion gap metabolic acidosis and hypokalemia

Respiratory acidosis and hyperkalemia

Anion gap metabolic acidosis and hypokalemia

Clinical approach to acid-base disorders for USMLE Step 3: High-Yield Physiology Lessons

ABG Interpretation - The First Glance

Normal Values:
- pH: 7.35-7.45
- PaCO₂: 35-45 mmHg
- HCO₃⁻: 22-26 mEq/L
Initial Assessment: Check the pH to determine acidosis (<7.35) or alkalosis (>7.45).
Identify Primary Disorder: Determine if the cause is respiratory (PaCO₂ is abnormal) or metabolic (HCO₃⁻ is abnormal).

⭐ 📌 ROME Mnemonic: In primary acid-base disorders, the pH and PaCO₂ move in Respiratory Opposite, Metabolic Equal directions.

ROME Mnemonic for Acid-Base Disorders

Anion Gap - Mind The Gap

The Anion Gap (AG) estimates unmeasured anions in the plasma, primarily albumin. A high AG is a hallmark of certain metabolic acidoses.
Formula: $AG = [Na⁺] - ([Cl⁻] + [HCO₃⁻])$
Normal range: 8-12 mEq/L.
For every 1 g/dL decrease in albumin below 4.0, add 2.5 to the calculated AG.

📌 MUDPILES for High AG Metabolic Acidosis (HAGMA):

Methanol
Uremia
Diabetic Ketoacidosis
Propylene glycol
Iron / Isoniazid
Lactic Acidosis
Ethylene glycol
Salicylates

⭐ Ethylene glycol (antifreeze) toxicity classically presents with HAGMA and calcium oxalate crystals (envelope-shaped) in urine.

Compensation Check - The Body's Rebalance

The body strives for pH balance via an opposing system:
- Lungs compensate for metabolic disorders (fast: minutes to hours).
- Kidneys compensate for respiratory disorders (slow: hours to days).
Metabolic Acidosis: Respiratory compensation.
- Calculate expected PaCO₂ using Winter's Formula: $PaCO₂ = (1.5 \times [HCO₃⁻]) + 8 \pm 2$.
- If measured PaCO₂ > expected → concurrent respiratory acidosis.
- If measured PaCO₂ < expected → concurrent respiratory alkalosis.
Metabolic Alkalosis:
- Expected PaCO₂ ↑ by ~0.7 mmHg for every 1 mEq/L ↑ in $[HCO₃⁻]$.
Respiratory Disorders: 📌 Use the 1/2/4/5 rule for expected $[HCO₃⁻]$ change per 10 mmHg change in PaCO₂.
- Acute Acidosis: ↑ 1
- Acute Alkalosis: ↓ 2
- Chronic Acidosis: ↑ 4
- Chronic Alkalosis: ↓ 5

⭐ If the measured PaCO₂ in a metabolic acidosis case does not match the value predicted by Winter's formula, a mixed acid-base disorder is present.

Mixed Disorders - The Final Puzzle

Suspect when compensation is inadequate or excessive, or if pH is normal with abnormal $pCO₂$ and $HCO₃⁻$.
The body rarely overcompensates. If compensation is more than expected, a second primary disorder is present.

Approach:

Determine the primary disorder.
Calculate the expected compensation.
If measured value ≠ expected → Mixed Disorder.

For HAGMA:

Calculate the delta-delta gap: $ΔAG / ΔHCO₃⁻$.
- Ratio <1: Suggests a co-existing non-anion gap metabolic acidosis.
- Ratio >2: Suggests a co-existing metabolic alkalosis.

⭐ A classic mixed disorder is a patient with diabetic ketoacidosis (HAGMA) who is also vomiting (metabolic alkalosis). The pH might be deceptively normal.

Flowchart? YES

Image placeholder? NO

Always start with pH to determine acidemia (<7.35) or alkalemia (>7.45).

PaCO₂ is the primary driver of respiratory disorders; HCO₃⁻ for metabolic.

For metabolic acidosis, always calculate the anion gap. If elevated, think MUDPILES.

Use Winter's formula to assess respiratory compensation in metabolic acidosis.

The delta-delta ratio helps identify a second, co-existing metabolic disorder.

Suspect a mixed disorder if compensation is inadequate or excessive.

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