Acid Base

Acid Base Disorders

Abdullah Alsakka

Objectives

• To provide a simple, systematic approach to interpreting arterial blood gas (ABG) samples
• Multiple formulas and rules exist to help guide us through the forest of diagnoses and complex problems
• All that is needed is a little clinical information obtained from a history and physical examination, a few readily available laboratory tests, and the knowledge of five simple steps
• Getting in the routine of performing these steps on each patient in which an ABG and electrolytes are performed will help decrease the rate of missed complex acid-base disturbances and hopefully improve patient care

Five Steps of Acid-Base Analysis

Step 1: Determine Acidemia or Alkalemia

• Acidemia: $\text{pH}<7.38$
• Alkalemia: $\text{pH}>7.42$

Step 2: Identify Primary Disturbance

• Look at ${\text{PCO}}_2$ and $\text{pH}$ relationship

Step 3: Assess Compensation

• Metabolic acidosis: ${\text{PCO}}_2=[1.5\times (\text{serum }{\text{HCO}}_3^{-})]+8(\pm 2)$
• Metabolic alkalosis: ${\text{PCO}}_2=\text{patient bicarbonate}-24(\text{normal bicarbonate})\times 0.06$
• Respiratory acidosis: $\uparrow {\text{PCO}}_2$ 10, $\uparrow {\text{HCO}}_3^{-}$ by 1 (acute) or 4 (chronic)
• Respiratory alkalosis: $\downarrow {\text{PCO}}_2$ 10, $\downarrow {\text{HCO}}_3^{-}$ by 2 (acute) or 5 (chronic)

Step 4: Check for Anion Gap

• Anion Gap Metabolic Acidosis (AGMA): $\text{AG}=\text{Na}-({\text{HCO}}_3^{-}+{\text{Cl}}^{-})$
• If AG $>12$, an AGMA is present

Step 5: Identify Additional Metabolic Disturbances

For AGMA:

• Calculate $\Delta \text{Gap}=\Delta \text{AG}-\Delta {\text{HCO}}_3^{-}=(\text{AG}-12)-(24-{\text{HCO}}_3^{-})$
• If $\Delta \text{Gap}>6$: Combined AGMA and Metabolic Alkalosis
• If $\Delta \text{Gap}<-6$: Combined AGMA and NAGMA
• If between -6 and 6: No additional metabolic disorders

For NAGMA:

• For every 1 mEq/L $\uparrow {\text{Cl}}^{-}$, there should be a 1 mEq/L $\downarrow {\text{HCO}}_3^{-}$ (+5)
• If ${\text{HCO}}_3^{-}$ decrease is less than predicted: NAGMA and metabolic alkalosis

Detailed Step 2: Primary Respiratory or Metabolic Disturbance

Look at ${\text{PCO}}_2$ and pH relationship:

• If pH and ${\text{PCO}}_2$ are going in the same direction → Metabolic disturbance

• If pH and ${\text{PCO}}_2$ are going in different directions → Respiratory disturbance

Detailed Step 3: Compensation Formulas

• Metabolic acidosis: ${\text{PCO}}_2=[1.5\times (\text{serum }HC{O}_3)]+8(\pm 2)$
• Metabolic alkalosis: $\uparrow PC{O}_2=0.6\times \uparrow HC{O}_3(\pm 2)$
• Respiratory acidosis: $\uparrow PC{O}_2$ 10, $\uparrow HC{O}_3$ by 1 (acute) or 4 (chronic)
• Respiratory alkalosis: $\downarrow PC{O}_2$ 10, $\downarrow HC{O}_3$ by 2 (acute) or 5 (chronic)

Detailed Step 4: Anion Gap Calculation

• Anion Gap: $AG=Na-(HC{O}_3+Cl)$
• If AG > 12: Anion Gap Metabolic Acidosis (AGMA) is present

Detailed Step 5: Additional Metabolic Disturbances

For AGMA:

• Calculate $\Delta \text{Gap}=\Delta \text{AG}-\Delta {\text{HCO}}_3=(\text{AG}-12)-(24-{\text{HCO}}_3)$
• If $\Delta \text{Gap}>6$: Combined AGMA and metabolic alkalosis
• If $\Delta \text{Gap}<-6$: Combined AGMA and NAGMA

For NAGMA:

• For every 1 mEq/L $\uparrow$ Cl, there should be a 1 mEq/L $\downarrow$ HCO₃ (+5)
• If HCO₃ decrease is less than predicted: NAGMA and metabolic alkalosis

Metabolic Acidosis

In the presence of a $\text{pH}<7.38$, metabolic acidosis is diagnosed as a primary condition when the ${\text{pCO}}_2$ is $<40$ mmHg or the bicarbonate is $<24$ mEq/L.

Classification and Pathophysiology

Metabolic acidosis can be further classified based on the presence of an anion gap. The anion gap reflects the balance between positively and negatively charged particles in the blood.

• Sodium is the only significant positively charged particle that is measured
• Measured anions are chloride and bicarbonate
• Anion gap formula: $\text{Na}-(\text{Cl}+{\text{HCO}}_3)$

Important Considerations

Low Albumin Adjustment:

• Albumin has several negative charges
• For every 1 gram drop in serum albumin, the anion gap decreases by 2.5
• A patient with calculated AG of 10 and 2 gram albumin drop may actually have AGMA (recalculated AG = 15)

AGMA Detection:

• Only a few conditions commonly cause AGMA
• In mixed acid-base disorders, anion gap elevation may be the only signal of metabolic acidosis
• Causes are divided into four main categories: renal failure, ketoacidosis, toxins, and lactic acidosis

Anion Gap Metabolic Acidosis (AGMA) - CAT MUDDILES Mnemonic

• C - Cyanide, Carbon monoxide
• A - Analgesics (massive NSAID, acetaminophen), Arsenic, Alcoholic ketoacidosis
• T - Toluene, Toxins
• M - Methanol, Metformin
• U - Uremia
• D - Diabetic ketoacidosis
• D - Paraldehyde, Phenformin
• I - Iron, Isoniazid
• L - Lactic acidosis
• E - Ethylene glycol
• S - Salicylates

Osmol Gap Calculation

In any patient with an AGMA, calculate an osmol gap to identify potentially life-threatening toxic alcohol ingestion:

• Osmol gap = Measured osmolality - Calculated osmolality
• Calculated osmolality = $2(\text{Na})+\text{Glc}/18+\text{BUN}/2.4+\text{ETOH}/4.6$

Clinical Example: Methanol Toxicity

Case: 32-year-old man with depression and alcohol abuse presents with altered mental status.

Laboratory Values:

• ABG: pH 6.9, pCO₂ 29, pO₂ 100
• Metabolic panel: Na 140, Cl 101, HCO₃ 5

Five-Step Analysis:

1. Step 1: Acidosis (pH < 7.38)
2. Step 2: Metabolic (low HCO₃)
3. Step 3: Expected $pC{O}_2=1.5(HC{O}_3^{-})+8=15$, but actual $pC{O}_2$ is higher (29) → Respiratory acidosis also present (possibly secondary to CNS depression)
4. Step 4: $AG=140-(101+5)=34$ → AGMA present
5. Step 5: Delta gap = $(34-12)-(24-5)=3$ → No additional metabolic disorders

Diagnosis: Anion gap metabolic acidosis and respiratory acidosis

Additional finding: Osmol gap of 174, methanol level of 510 mg/dL

Non-Anion Gap Metabolic Acidosis (NAGMA)

Pathophysiology

A NAGMA is due to either GI or renal losses of bicarbonate. GI-mediated and renally mediated losses can be distinguished by obtaining urine electrolytes and calculating the urine anion gap.

Urine Anion Gap

• Formula: $\text{Na}+\text{K}-\text{Cl}$

• The urine anion gap represents the difference between spot urine positive ions and negative ions

• Interpretation: If an excess of negatively charged ions is present, the acidemia is due to the kidney

Clinical Example: Diarrhea

Case: 68-year-old man who recently took antibiotics for a skin infection presents with 10 episodes of watery diarrhea per day for the last 5 days.

Laboratory Values:

• ABG: pH 7.34, pCO₂ 34, pO₂ 80
• Metabolic panel: Na 135, Cl 108, HCO₃ 18

Five-Step Analysis:

1. Step 1: Acidosis (pH < 7.38)
2. Step 2: Metabolic (low HCO₃)
3. Step 3: Expected $pC{O}_2=1.5(HC{O}_3^{-})+8=35$ → Appropriate compensation
4. Step 4: $AG=135-(108+18)=9$ → No AGMA
5. Step 5: $C{l}^{-}$ increased by 8 and $HC{O}_3^{-}$ decreased by 6 → No metabolic alkalosis

Diagnosis: NAGMA due to diarrhea

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Respiratory Acidosis

Pathophysiology

Respiratory acidosis is characterized by an elevation in $pC{O}_2$ and a decrease in blood pH due most commonly to hypoventilation. It results from conditions that decrease the ability of the lungs to excrete carbon dioxide at a rate to keep up with the body’s production.

Differential Diagnosis

Causes include:

• Central nervous system depression (sedatives, CNS disease, sleep apnea)
• Pleural disease (large pneumothorax or pleural effusion)
• Lung disease (ARDS, COPD, pulmonary edema, severe pneumonia)
• Acute airway obstruction (laryngospasm, sleep apnea)
• Neuromuscular disorders (GBS, myasthenia gravis, botulism)
• Thoracic cage injury (flail chest)
• Ventilator dysfunction

Compensation Mechanism

• The kidney compensates for primary respiratory acidosis by retaining bicarbonate
• This compensation occurs over hours to days and is generally at a maximum within four days
• The rate of onset can be determined by the degree of renal compensation (increase in ${\text{HCO}}_3^{-}$)

Acute vs Chronic Differentiation

Acute respiratory acidosis:

• pH decreases by 0.08 units for each increase of 10 mmHg in $pC{O}_2$ from baseline (40 mmHg)

Chronic respiratory acidosis:

• pH decreases by 0.03 units for every increase of 10 mmHg in $pC{O}_2$

Clinical Importance: Differentiating acute from chronic conditions is crucial as it may alert clinicians to patients who are rapidly deteriorating and may require emergent intubation versus those with chronic disease who are less imminently at risk.

Clinical Example: COPD Exacerbation

Case: 70-year-old smoker presents with acute onset of shortness of breath.

Laboratory Values:

• ABG: pH 7.30, pCO₂ = 60 mmHg, pO₂ 60 mmHg
• Metabolic panel: Na 135, Cl 100, HCO₃ 30

Five-Step Analysis:

1. Step 1: Acidosis (pH < 7.38)
2. Step 2: Respiratory (elevated pCO₂)
3. Step 3: Acute on chronic. $pC{O}_2$ increased by 20, so $HC{O}_3^{-}$ should increase by 2 if acute and 8 if chronic. Since $HC{O}_3^{-}$ increased from 24 to 30 (6), acute on chronic respiratory acidosis is present
4. Step 4: $AG=135-(100+26)=9$ → No anion gap metabolic acidosis
5. Step 5: Not applicable

Diagnosis: Acute on chronic respiratory acidosis due to COPD exacerbation

Metabolic Alkalosis

Pathophysiology

Metabolic alkalosis is characterized by an increase in the serum bicarbonate concentration.

Causes

Common etiologies include:

• Volume contraction (vomiting, NG suction, loop or thiazide diuretics)
• Excess glucocorticoids or mineralocorticoids (e.g., Cushing’s syndrome)
• Hypokalemia
• Bartter’s syndrome
• Alkali ingestion/infusion
• Post-hypercapnic alkalosis

Diagnostic Approach: Urine Chloride

To differentiate the most common cause (volume depletion) from other causes, measure urine chloride:

• Urine chloride < 10 mEq/L: Volume depletion (saline-responsive)

• Urine chloride > 10 mEq/L: Other causes (saline-resistant)

Clinical Example: Vomiting

Case: 20-year-old student presents with excessive vomiting after binge drinking.

Laboratory Values:

• ABG: pH 7.50, pCO₂ 44, pO₂ 100
• Metabolic panel: Na 138, Cl 100, HCO₃ 30

Five-Step Analysis:

1. Step 1: Alkalosis (pH > 7.42)
2. Step 2: Metabolic (elevated HCO₃)
3. Step 3: Expected increase in $pC{O}_2$ = 0.6 × elevation of $HC{O}_3^{-}\pm 2$
   • $HC{O}_3^{-}$ elevation = 30 - 24 = 6
   • Expected $pC{O}_2$ increase = 0.6 × 6 = 3.6
   • Actual $pC{O}_2$ increase = 44 - 40 = 4
   • Since 4 is within ±2 of 3.6, there is appropriate compensation
4. Step 4: $AG=138-(100+30)=8$ → No AGMA
5. Step 5: Not applicable

Diagnosis: Metabolic alkalosis secondary to vomiting

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Respiratory Alkalosis

Pathophysiology

Respiratory alkalosis is characterized by a decrease in $pC{O}_2$ and an elevation in blood pH. The $p{O}_2$ can be used to distinguish between lung disease and other causes of hyperpnea (e.g., fever).

Causes

Primary respiratory alkalosis etiologies include:

• CNS disease (CVA)
• Toxins (Salicylates)
• High altitude
• Severe anemia
• Pregnancy
• Lung disease/hypoxia (asthma, pneumonia, PE, pulmonary edema, pulmonary fibrosis)
• Anxiety
• Cirrhosis of the liver
• Fever (Sepsis)
• Ventilator dysfunction

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Clinical Example: Panic Attack

Case: 22-year-old woman presents with 4 hours of numbness in both hands typical of previous episodes of anxiety.

Laboratory Values:

• ABG: pH 7.48, pCO₂ 30 mmHg, pO₂ 86 mmHg
• Metabolic panel: Na 140, Cl 110, HCO₃ 22

Five-Step Analysis:

1. Step 1: Alkalosis (pH > 7.42)
2. Step 2: Respiratory (decreased pCO₂)
3. Step 3: Acute. Drop in $pC{O}_2$ by 10 corresponds to a drop in $HC{O}_3^{-}$ by 2 if acute and 5 if chronic.
   • $HC{O}_3^{-}$ drop = 24 - 22 = 2
   • This matches acute compensation pattern → Acute respiratory alkalosis
4. Step 4: AG = $140-(110+22)=8$ → No AGMA
5. Step 5: Not applicable

Diagnosis: Acute respiratory alkalosis secondary to a panic attack

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Case 1

Patient: 40-year-old male with abdominal pain Laboratory Values:

• pH 7.42, pCO₂ 33
• Na 141, HCO₃ 24, Cl 90

Acidemia/ Alkalemia: Normal leaning acidosis PH - pCO2 low | RA

Compensation: 40-33 drop of 7 |

Anion gap = 141 - (90 + 24) = 27 | AGMA

Delta Gap: $(AG-12)-(24-HC{O}_3)=(27-12)-(24-24)=15$. | MA

Respiratory Alkalosis + Anion Gap Metabolic Acidosis + Metabolic Alkalosis.

Case 2

Patient: Chronic alcoholic with vomiting and abdominal pain Laboratory Values:

• Na⁺ = 137, pH = 7.40
• K⁺ = 3.8, pCO₂ = 41
• Cl^- = 90, HCO₃^- = 22

Normal ph, pCO₂ = normal

Compensation: HCo3 is low = Metabolic Acidosis

Anion Gap: AG = $137-(90+22)=25$. This is high, indicating an AGMA (likely alcoholic ketoacidosis).

Delta Gap = $(25-12)-(24-22)=13-2=11$.

Since the Delta Gap is > 6, there is a co-existing Metabolic Alkalosis

Mixed Anion Gap Metabolic Acidosis and Metabolic Alkalosis.

Case 3

Patient: Diabetic with diarrhea and cough. CXR reveals infiltrate. Laboratory Values:

• pH 7.31, pCO₂ 10
• Na 123, HCO₃ 5, Cl 99

Impression pH Low, pCO2 Low Metabolic Acidosis

Compensation:
Expected pCO₂ = $[1.5\times 5]+8=15.5$. The actual pCO₂ is 10, which is lower than expected. This indicates a superimposed Respiratory Alkalosis (likely from the pneumonia/sepsis).

Anion Gap: AG = $123-(99+5)=19$. This is high, indicating AGMA (likely DKA).

Delta Gap = $(19-12)-(24-5)=7-19=-12$. * Since the Delta Gap is < -6, there is also a Non-Anion Gap Metabolic Acidosis (NAGMA) (explained by the history of diarrhea).

Diagnosis AGMA + NAGMA + Respiratory Alkalosis.

Case 4

Patient: Alcoholic with vomiting Laboratory Values:

• pH 7.20, pCO₂ 25
• Na 130, HCO₃ 10, Cl 80

Impression pH Low, pCO2 Low Metabolic Acidosis

Compensation:
Expected pCO₂ = $[1.5\times 10(HCO3)]+8=23$. The actual pCO₂ is 25, which is within the expected range ($\pm 2$) for compensation.

Anion Gap: AG = $130(NA)-(80(Cl)+10(HCO3))=40$. This is very high, indicating AGMA (likely alcoholic ketoacidosis).

Delta Gap = $(40-12)-(24-10)=28-14=14$. Since the Delta Gap is > 6, there is a co-existing Metabolic Alkalosis (from vomiting).

Diagnosis Mixed Anion Gap Metabolic Acidosis and Metabolic Alkalosis.

Case 5

Patient: Man with arthritis with confusion, shortness of breath, and diaphoresis - aspirin overdose Laboratory Values:

• pH 7.30, pCO₂ 18
• Na 147, HCO₃ 16, Cl 108

Impression pH is 7.30 (Acidemia).

Compensation:
Expected pCO₂ = $[1.5\times 16]+8=32$. The actual pCO₂ is 18, which is much lower than expected. This signifies a primary Respiratory Alkalosis.

Anion Gap: AG = $147-(108+16)=23$. This is high, indicating AGMA.

Delta Gap $(23-12)-(24-16)=11-8=3$. * The Delta Gap is between -6 and 6, so there are no other metabolic disorders.

Diagnosis Mixed Anion Gap Metabolic Acidosis and Respiratory Alkalosis, likely due to salicylate toxicity.

Case 6

Patient: COPD patient with shortness of breath Laboratory Values:

• pH 7.18, pCO₂ 80
• Na 135, HCO₃ 30, Cl 93

Impression pH is 7.18 (Acidemia). & pCO2 80 (Alkalosis) - Respiratory acidosis

Compensation:
high gap

Anion Gap: AG = $135-(93+30)=12$. The anion gap is normal.

Diagnosis Acute-on-Chronic Respiratory Acidosis.

Case 7

Patient: Woman with Crohn’s disease with fever, vomiting, and diarrhea Laboratory Values:

• pH 7.36, pCO₂ 22
• Na 147, HCO₃ 14, Cl 121

Impression pH Low, pCO2 Low Metabolic Acidosis

Compensation:
Expected pCO₂ = $[1.5\times 14(HCO3)]+8=29$. The actual pCO₂ is 25

which is lower than expected, indicating a superimposed Respiratory Alkalosis (likely from fever/sepsis).

Anion Gap: AG = $147(NA)-(121(Cl)+14(HCO3))=12$.

The anion gap is normal. This is a Non-Anion Gap Metabolic Acidosis (NAGMA), caused by diarrhea.

Diagnosis Mixed Non-Anion Gap Metabolic Acidosis and Respiratory Alkalosis.

Case 8

Patient: Noncompliant patient with diabetes and cirrhosis with vomiting Laboratory Values:

• pH 7.46, pCO₂ 17
• Na 133, HCO₃ 15, Cl 84

Impression pH high (Alkalemia) - pco2 (Acidosis) Respiratory Alkalosis

Compensation:
Expected pCO₂ = $[1.5\times 15(HCO3)]+8=30$. The actual pCO₂ is 25

Anion Gap: AG = $133(NA)-(84(Cl)+15(HCO3))=34$.

This is very high, indicating an AGMA (likely DKA).

GAP: $(34(AG)-12)-(24-15(HCo3))=22-9=13$.

Since the Delta Gap is > 6, there is also a Metabolic Alkalosis (from vomiting).

Diagnosis Respiratory Alkalosis + Anion Gap Metabolic Acidosis + Metabolic Alkalosis.

Case 9

Patient: Healthcare professional with dizziness Laboratory Values:

• Na = 123
• pH = 7.55
• K⁺ = 3.1
• pCO₂ = 50
• Cl^- = 67
• HCO₃ = 43
• Glu = 125
• BUN = 25

Impression PH high - Alkalemia - HCO3 high alkalosis

Compensation:
HCO₃ has increased by 19 (43-24). Expected pCO₂ increase = $0.6\times 19=11.4$. Expected pCO₂ = $40+11.4=51.4$. The actual pCO₂ of 50 is appropriate compensation.

Anion Gap: AG = $123-(67+43)=13$. The anion gap is essentially normal.

Diagnosis Metabolic Alkalosis with appropriate respiratory compensation. The hypochloremia is a clue towards a saline-responsive cause like surreptitious vomiting or diuretic abuse.

Case 10

Patient: 25-year-old man brought to ED comatose by paramedic. No response to D50 and Narcan. Laboratory Values:

• Na⁺ = 141
• pH = 4.40 (Note: This appears to be a transcription error - likely pH 4.40 should be 7.40)
• K⁺ = 4.0
• pCO₂ = 40
• Cl = 103
• pO₂ = 84
• HCO₃^- = 25
• Glu = 90
• BUN = 14
• Urine Dip: Large ketone
• Measured Osmolarity: 338

Patient: 25-year-old comatose man. Labs: pH = 7.40 (assumed from note), pCO₂ = 40, HCO₃⁻ = 25, Na⁺ = 141, Measured Osm = 338.

1. Acidemia/Alkalemia: pH, pCO₂, and HCO₃ are all normal.
2. Anion Gap: AG = $141-(103+25)=13$. This is borderline normal/high.
3. Osmol Gap: The key to this case is the Osmol Gap, which is crucial in a comatose patient with a seemingly normal ABG.
   • Calculated Osmolality = $2(\text{Na})+\text{Glc}/18+\text{BUN}/2.4=2(141)+90/18+14/2.4=282+5+5.8=292.8$
   • Osmol Gap = Measured Osmolality - Calculated Osmolality = $338-292.8=45.2$.
   • A normal osmol gap is < 10-15. A gap of 45 is extremely high.

Diagnosis: Elevated Osmol Gap with a normal Anion Gap. This is highly suggestive of an early toxic alcohol ingestion (e.g., methanol or ethylene glycol). The patient has ingested the toxin (creating the osmol gap) but has not yet metabolized it into its acidic byproducts, which would later cause a severe AGMA.