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Acid-Base Rules – Summary


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

Respiratory Acidosis 1 -> 4
Respiratory Alkalosis 2 -> 5

Metabolic Acidosis - the ‘1.5 + 8 Rule’ -> expected PaCO2 at max compensation = 1.5 x
HCO3- + 8

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

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:

RAGMA – look for lactate, calculate Delta ratio, Stewart Equation

NAGMA – calculate Urinary anion gap, Steward Equation
Osmolarity – calculate Osmolar gap


CAUSES (Cohen & Woods classification)

Type A - Inadequate Oxygen Delivery

(i) anaerobic muscular activity (sprinting, generalised convulsions)

(ii) tissue hypoperfusion (shock, cardiac arrest, regional hypoperfusion -> mesenteric

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(iii) 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

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)

Causes of an Anion Gap Metabolic Acidosis – accumulation of organic acids or impaired H+



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

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Expanded Causes (MUDPILES)

Phenformin, Paracetamol, Pyroglutamic metabolic acidosis, Paraldehyde
Iron, isoniazid
Ethylene glycol, ethanol
Salicylates, solves

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


GI loss (diarrhoea, vomiting, enterostomies, fistulae, ileostomies)
Extra: RTA type 1

Expanded Causes (HARDUP)

Acetazolamide, Addison’s disease
Renal tubular acidosis
Diarrhoea, vomiting, ileostomies, fistulae

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

Delta Ratio

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

- indicates what has happen to the denominator (HCO3-)

- used in RAGMA to see whether change in HCO3- is appropriate (ie. whether there is a
RAGMA component to disorder)
- normal value = 1 to 1.5
- if normal there is only one pathology (uncomplicated RAGMA)


< 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

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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

- the osmolality is measured in lab

- calculated osmolarity = (2 x [Na+]) + [glucose] + [urea]
- the osmolar gap = Osmolality - Osmolarity
- 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
- 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 (MEPMELK)

P – isopropyl alcohol
Methylene glycol
Ethylene glycol

Causes of a Normal Osmolar Gap Metabolic Acidosis

- Pyroglutamic acid
- Salicyclates

Urinary Anion Gap

- 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 cations (UC).

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

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:

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(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.

Stewart Equation

- 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)

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 RAGMA + NAGMA

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