Acid-Base Interpretation

Reviewed and revised 5/5/12


1. pH – acidaemia or alkalaemia – net deviation from normal indicates presence of an acidosis or alkalosis

2. Assess the pattern – each of the simple disorders produce predictable changes in either PCO2 or HCO3-

3. Look for associated clues – certain conditions produce certain changes in biochemistry

4. Assess for compensation response

HCO3 will change for a 10mmHg change in PaCO2 (1-2-HCO3-4-5 rule)

Respiratory Acidosis 1 (acute) -> 4 (chronic)
Respiratory Alkalosis 2 (acute) -> 5 (chronic)

Metabolic Acidosis – the ‘1.5 + 8 Rule’ (Winter’s Rule) -> expected PaCO2 at max compensation = 1.5 x HCO3- + 8

Metabolic Alkalosis – the ‘Point Seven plus Twenty Rule’ -> expected pCO2 = 0.7 [HCO3] + 20

5. Other Indices in the Assessment of a Metabolic Acidosis

  • Lactate
  • Anion Gap
  • Delta ratio
  • Osmolar Gap
  • Urinary anion Gap
  • Stewart equation

When to calculate what:

  • HAGMA – look for lactate, calculate Delta ratio, Stewart Equation
  • NAGMA – calculate Urinary anion gap, Steward Equation
  • Osmolarity – calculate Osmolar gap


(Cohen & Woods classification)

Type A – Inadequate Oxygen Delivery

  • anaerobic muscular activity (sprinting, generalised convulsions)
  • tissue hypoperfusion (shock, cardiac arrest, regional hypoperfusion -> mesenteric ischaemia)
  • reduced tissue oxygen delivery (hypoxaemia, anaemia) or utilisation (CO poisoning)

Type B – No Evidence of Inadequate Tissue Oxygen Delivery

B1: associated with underlying diseases

  • LUKE: leukaemia, lymphoma
  • TIPS: thiamine deficiency, infection, pancreatitis, short bowel syndrome
  • FAILURES: hepatic, renal, diabetic failures

B2: associated with drugs & toxins

  • phenformin
  • cyanide
  • beta-agonists
  • methanol
  • adrenaline
  • salicylates
  • nitroprusside infusion
  • ethanol intoxication in chronic alcoholics
  • anti-retroviral drugs
  • paracetamol
  • salbutamol
  • biguanides
  • fructose
  • sorbitol
  • xylitol
  • isoniazid

B3: associated with inborn errors of metabolism

  • congenital forms of lactic acidosis with various enzyme defects (eg pyruvate dehydrogenase deficiency)


Anion gap = (Na+ + K+) – (Cl- + HCO3-)

  • normal 12 to 16
  • the normal anion gap depends on serum phosphate and serum albumin
  • the normal AG = 0.2 x [albumin] (g/L) + 1.5 x [phosphate] (mmol/L)

Can be more simply calculated as (Na+) – (Cl- + HCO3-)

  • normal 8 to 12

Causes of an High Anion Gap Metabolic Acidosis (HAGMA) – accumulation of organic acids or impaired H+ excretion

Left total knee replacement (LTKR)

  • Lactate
  • Toxins – methanol, metformin, penformin, paraldehyde, propylene glycol, pyroglutamic acidosis, acid, Fe, isoniazid, ethanol, ethylene glycol, salicylates, solvent
  • Ketones
  • Renal Failure

Expanded Causes (CAT MUDPILES)

  • CO, CN
  • Alcoholic ketoacidosis
  • Toluene
  • Methanol
  • Uraemia
  • DKA
  • Phenformin, Paracetamol, Pyroglutamic metabolic acidosis, Paraldehyde
  • Iron, isoniazid
  • Lactate
  • Ethylene glycol, ethanol
  • Salicylates

Causes of a Non-anion Gap Metabolic Acidosis (NAGMA) – loss of HCO3- from ECF


  • Chloride
  • Acetazolamide/Addisons
  • GI loss (diarrhoea, vomiting, enterostomies, fistulae, ileostomies)
  • Extra: RTA type 1


  • Addisons
  • Bicarb loss (GI or renal, incl RTA)
  • Chloride
  • Drugs (e.g. acetazolamide, acids)

Expanded Causes (HARDUP)

  • Hyperchloraemia
  • Acetazolamide, Addison’s disease
  • Renal tubular acidosis
  • Diarrhoea, vomiting, ileostomies, fistulae
  • Ureteroenterostomies
  • Pancreatoenterostomies


  • Ureteroenterostomies
  • Small bowel fistula
  • Excess Chloride
  • Diarrhoea
  • Carbonic anhydrase inhibitors
  • Renal tubular acidosis
  • Addisson’s disease
  • Pancreatoenterostomies

Causes of a Low Anion Gap

  • Decrease in unmeasured anions (albumin, dilution)
  • Increase in unmeasured cations (multi-myeloma, hypercalcaemia, hypermagnesaemia, lithium OD, bromide OD, polymixin B)
  • Non random analytical errors (increased Na+, increased viscosity, iodide ingestion, increased lipids)


Delta ratio = the increase in Anion Gap/the decrease in HCO3-

  • indicates what has happen to the denominator (HCO3-)
  • used in HAGMA to see whether change in HCO3- is appropriate (i.e. whether there is a coexistant NAGMA or metabolic alkalosis component to disorder)
  • normal value = 1 to 1.5
  • if normal there is only one pathology (uncomplicated HAGMA)


  • < 0.4 – hyperchloraemic normal anion gap acidosis
  • 0.4 – 0.8 – consider combined high AG & normal AG acidosis BUT note that the ratio is often < 1 in acidosis associated with renal failure
  • 1 – 2 – usual for uncomplicated high-AG acidosis (lactic acidosis: average value 1.6, DKA: around 1)
  • > 2 – a high delta ratio – > an elevated bicarbonate at onset of the metabolic acidosis -> pre-existing metabolic alkalosis or compensated respiratory acidosis.


Osmolar gap = Osmolality – Osmolarity

  • osmolality is measured in lab
  • calculated osmolarity = (2 x [Na+]) + [glucose] + [urea]
  • an osmolar gap > 10 mOsm/l is often stated to be abnormal


  • indirect evidence for the presence of an abnormal solute which is present in significant amounts.
  • ethanol, methanol & ethylene glycol -> will cause an elevated osmolar gap.
  • NB: To convert ethanol levels in mg/dl to mmol/l divide by 4.6. For example, an ethanol level of 0.05% is 50mg/dl. Divide by 4.6 gives 10.9mmols/l

Causes of Raised Osmolar Gap (MIME ELK)

  • Methanol/mannitol
  • Isopropyl alcohol
  • Methylene glycol
  • Ethylene glycol
  • Ethanol
  • Lactate
  • Ketones

Causes of a Normal Osmolar Gap Metabolic Acidosis

  • Pyroglutamic acid
  • Salicyclates


Urinary Anion Gap = [Na+]+ [K+] – [Cl-]

  • the cations normally present in urine are Na+, K+, NH4+, Ca++ and Mg++.
  • the anions normally present are Cl-, HCO3-, sulphate, phosphate and some organic anions.
  • only Na+, K+ and Cl- are commonly measured in urine so the other charged species are the unmeasured anions (UA) and unmeasured cations (UC).

Clinical Use

  • the urinary anion gap can help to differentiate between GIT and renal causes of a hyperchloraemic metabolic acidosis.
  • hyperchloraemic acidosis can be caused by:
    (i) loss of base via the kidney (eg renal tubular acidosis)
    (ii) loss of base via the bowel (eg diarrhoea), or
    (iii) gain of mineral acid (eg HCl infusion)
  • if the acidosis is due to loss of base via the bowel then the kidneys can respond appropriately by increasing ammonium excretion to cause a net loss of H+ from the body -> the UAG would tend to be decreased -> increased NH4+ (with presumably increased Cl-) -> increased UC -> decreased UAG.
  • if the acidosis is due to loss of base via the kidney -> it is not able to increase ammonium excretion and the UAG will not increase.


  • pH is dependent on other ions in solution not just H+ and HCO3-
  • there are dependent and independent variables


  • H+
  • OH-
  • HCO3-
  • CO32-
  • HA (weak acids)
  • A- (weak bases)


  • PaCO2
  • ATOT (total of weak non-volatile acids)
  • SID

Strong Ion Difference

  • a strong ion = an ion that totally dissociates at a given pH
  • SID = strong cations – strong anions
  • SID = (Na+ + K+ + Ca2+ +Mg2+) – (Cl- — other anions)

Modified SID = (Na+ – K+) – Cl-

  • SID > 0 = alkalosis
  • SID < 0 = acidosis
  • normal SID of plasma = 40mEq/L (slightly alkalaemic)
  • any movement from this is roughly equal to the standard base excess

Simple SID calculator

  • Expected BE = (Na+ – Cl-) – 38
  • if expected BE < observed BE -> there is a mixed HAGMA + NAGMA


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  1. langa says

    hi jeremy, quick question, does ethanol not just give you an osmolar gap without the high anion gap? i might be getting this wrong , please advise


    • says

      Hi Langa
      Different types of alcohol are theoretically much the same.
      Unmetabolised they cause an osmolar gap without an anion gap.
      The osmolar gap decreases over time as the anion gap increases, reflecting metabolism into carboxylic acids.
      So, most alcohols cause both an osmolar gap and an anion gap.