acid_base_disorders

Metabolic Acidosis: Anion Gap

• Anion Gap (AG) helps classify metabolic acidosis as high-gap (HAGMA) or normal-gap (NAGMA).
• Formula (no potassium):
  $\text{Anion Gap} = [\text{Na}^+] - [\text{Cl}^-] - [\text{HCO}_3^-]$
  Reference range: $8 \leq \text{AG} \leq 12\,\text{mmol/L}$ (± about 4 mmol/L).
• Sometimes potassium is included: $\text{AG}<em>{\text{with K}} = [\text{Na}^+] + [\text{K}^+] - [\text{Cl}^-] - [\text{HCO}</em>3^-]$
• Note on potassium: relative to the three other ions, [K+] is low and typically does not change much, so omitting it from the equation has limited clinical impact.

HAGMA and NAGMA

• High Anion Gap Metabolic Acidosis (HAGMA): Gain of unmeasured anions (endogenous or exogenous).
• Normal Anion Gap Metabolic Acidosis (NAGMA): Hyperchloremia and/or bicarbonate loss lead to a normal AG.

Common etiologies (summary, from slides)

• HAGMA etiologies include:
  • Renal failure
  • Iatrogenic causes: saline infusion, parenteral nutrition, carbonic anhydrase inhibitors
  • Ketoacidosis: diabetic, alcoholic, starvation
  • Lactic acidosis
  • Toxins: methanol, ethylene glycol, salicylates, metformin, pyroglutamic acid
  • Renal losses: renal tubular acidosis, ureteroenterostomy
• NAGMA etiologies include:
  • Hyperchloremia
  • bicarbonate loss (e.g., bicarbonate-rich fluids loss or GI loss)
  • GI losses such as diarrhoea and biliary/pancreatic drainage

Lactic Acidosis

• Type A: Imbalance between oxygen supply and demand (hypoxia-related)
• Type B: Altered metabolism (not due to overt hypoxia)
  • Reduced supply/ delivery problems: hypoxaemia, anaemia
  • Impaired tissue utilisation: CO poisoning
  • Hypoperfusion: Shock
  • Type B1: Underlying disease (e.g., leukaemia/lymphoma), thiamine deficiency, infection, pancreatitis, renal or hepatic failures, increased demand (e.g., anaerobic muscle activity, seizures, sprinting)
  • Type B2: Drugs (e.g., beta-agonists, salicylates, cyanide, ethanol, methanol)
  • Type B3: Inborn errors of metabolism

Other Considerations

• Hypoalbuminaemia and the AG:
  • Albumin carries negative charges (anionic). Low albumin lowers the measured AG.
  • Correction: for every 10 g/L below normal albumin, add approximately 2.5 to the anion gap.

Delta Ratio (Δ ratio)

• Used to determine whether there is a 1:1 relationship between the increase in AG and the decrease in HCO3−.
• Definition:
  $\Delta \text{Ratio} = \frac{\Delta \text{AG}}{\Delta [\text{HCO}<em>3^-]}$ where: $\Delta \text{AG} = \text{AG}</em>{\text{measured}} - \text{AG}<em>{\text{normal}}$ and $\Delta [\text{HCO}</em>3^-] = [\text{HCO}<em>3^-]</em>{\text{normal}} - [\text{HCO}<em>3^-]</em>{\text{measured}}$
• Interpretation (from slides):
  • $\Delta \text{Ratio} < 0.4$: associated hyperchloremic NAGMA
  • $0.4 \le \Delta \text{Ratio} \le 0.8$: consider a combination of HAGMA and NAGMA
  • $1 \le \Delta \text{Ratio} \le 2$: uncomplicated HAGMA
  • $\Delta \text{Ratio} > 2$: pre-existing metabolic alkalosis or compensation to chronic respiratory acidosis

Causes of Low Anion Gap

• Causes of a low anion gap include increased unmeasured cations or artefacts.
• Common listed causes (from Toxicology Handbook/table):
  • Artefactual Hyperchloraemia
  • Hypercalcaemia
  • Hypoalbuminaemia
  • Iodism
  • Hypermagnesaemia
  • Bromism
  • Lithium intoxication
  • Hypertriglyceridaemia
  • Multiple myeloma

Base Excess and Standard Base Excess

• Base excess (BE):
  • Definition: the amount of acid or base needed to return the blood sample pH to 7.40 under standard conditions (37°C and a PaCO2 of 40 mmHg, i.e., 5.3 kPa). BE isolates the metabolic component by removing respiratory effects.
• Standard Base Excess (SBE):
  • Definition: the dose of acid or base required to return the pH of an anaemic blood sample to 7.40, calculated for a haemoglobin (Hb) of 50 g/L.
  • Rationale: Haemoglobin buffers principally within intravascular space; SBE reflects buffering of the whole extracellular fluid, not just intravascular Hb-buffered fluid.

Causes of Metabolic Alkalosis

• Chronic hypercapnia can contribute.
• GI losses: vomiting, NG losses (chloride loss).
• Renal losses: diuretics, primary hyperaldosteronism, Cushing’s syndrome, Bartter’s syndrome.
• Volume contraction and hypochloraemia.
• Hypokalaemia.
• Administration of bases: antacids.

Summary of Acid–Base Assessment (Stepwise Approach)

• Step 1: Determine acidemia or alkalemia by pH (< 7.35 or > 7.45).
• Step 2: Identify primary disorder as respiratory vs metabolic (acidosis vs alkalosis).
• Step 3: Calculate the anion gap to identify HAGMA vs NAGMA (AG = $[\text{Na}^+] - [\text{Cl}^-] - [\text{HCO}_3^-]$; normal 8–12).
• Step 4: Check degree of compensation using expected PaCO2 (for metabolic disorders) or expected HCO3− (for respiratory disorders).
• Step 5: Determine the delta ratio to assess mixed disorders and/or chronicity.

Compensation in Metabolic Acidosis and Alkalosis (Step 4)

• Metabolic acidosis:
  • Expected PaCO2 (mmHg) = $(1.5 \times [\text{HCO}_3^-]) + 8$
  • Alternatively: for every 1 mmol/L decrease in HCO3−, PaCO2 should decrease by $1.3\ \text{mmHg}$.
• Metabolic alkalosis:
  • Expected PaCO2 (mmHg) = $(0.7 \times [\text{HCO}_3^-]) + 20$
  • Alternatively: for every 1 mmol/L increase in HCO3−, PaCO2 should increase by $0.6\ \text{mmHg}$.
• Conversion note: to convert mmHg to kPa, divide by $7.5$ (i.e., $\text{PaCO}<em>2\ ( ext{kPa}) = \text{PaCO}</em>2\ (\text{mmHg}) / 7.5$).

Step 4 cont: Respiratory acid–base disorders

• Acute respiratory acidosis:
  • For every 10 mmHg increase in PaCO2, HCO3− should rise by 1 mmol/L (acute).
• Chronic respiratory acidosis:
  • For every 10 mmHg increase in PaCO2, HCO3− should rise by 4 mmol/L (chronic).
• Acute respiratory alkalosis:
  • For every 10 mmHg decrease in PaCO2, HCO3− should decrease by 2 mmol/L (acute).
• Chronic respiratory alkalosis:
  • For every 10 mmHg decrease in PaCO2, HCO3− should decrease by 5 mmol/L (chronic).
• Step 5: Determine the delta ratio as above to evaluate mixed disorders.

Observational Acid-Base Patterns (Table 4 – Kellum reference)

• The table links HCO3−, PaCO2, and SBE across a matrix of disorders:
  • Metabolic acidosis, metabolic alkalosis, acute and chronic respiratory acidosis/alkalosis, etc.
• Focused interpretation:
  • Metabolic acidosis: low HCO3−; PaCO2 adjusts