Approach to Acid-Base Problems

Dr Frank Daly
MBBS, FACEM

Clinical Toxicologist & Emergency Physician

Royal Perth Hospital, Western Australia
University of Western Australia
Western Australian Poisons Information Centre
New South Wales Poisons Information Centre

Western Australian Toxicology Service

Introduction
• Acid-base pairs first described by Lowry (UK) and Brönsted
(Denmark) in 1923
• Changes in serum pH minimised by three compensatory
systems:
– Physiologic buffers
• Bicarbonate-carbonic acid system
• Haemoglobin and other protein buffers
• Bone
– Lungs
– Kidneys
Introduction

• Acid-base abnormalities indicate underlying

disease, rather than representing a diagnosis
themselves
– Metabolic acidosis has several potentially lethal causes
– Once you have established that an acidosis exists you
should look for and treat life-threatening causes

• A stepwise clinical approach is vital

History and Physical Examination
• Pay particular attention to:
– Past medical history (e.g. diabetes, renal failure)
– Medications (e.g. metformin)
– Potential chemical ingestions (e.g. methanol)
– Diarrhoea or vomiting
– Level of consciousness
– Respiratory rate
– Hydration and urine output
Disney JD. Rosen’s Emergency Medicine: Concepts and Clinical
Practice 5th Edition, Mosby 2002
‘Rule of Fives’
Whittier WL, Rutecki GW. Dis Mon 2004;50:117-162

1. What is the pH (primary acid-base

disturbance)?
2. Determine whether the primary process is
respiratory, metabolic or both
3. Calculate the anion gap
4. Check the degree of compensation
5. Determine if there is a 1:1 relationship between
anions in the blood (the ‘delta gap’)
Case 1

An adult male presents with abdominal pain,

vomiting and ataxia. He is breathing fast
• pH 7.10 • Na+ 145 mEq/L
• PaCO2 22 mmHg • K+ 2.7 mEq/L
• PaO2 95 mmHg • Cl- 105 mEq/L
• HCO3 8 mEq/L • Urea 7.1 mmol/L
• Cr 88 mcmol/L
• Osmolality 360 mOsm/L • Glucose 4.4 mmol/L
What is the primary acid-base
disturbance?

• Acidemia exists if pH < 7.40

• Alkalemia exists if pH > 7.44

• The body will always attempt to compensate
for an acid-base disturbance, but complete
compensation cannot occur (the pH does not
return to normal)

• Therefore, if a single acid-base disturbance

exists, the primary process can be identified by
the serum pH
• If there is significant abnormality of HCO3 and
PaCO2 with normal pH, there must be at least
two counter-acting pathologies
Case 1

• The pH is 7.10

• There is acidemia
Respiratory, metabolic or both?
• Respiratory acidosis- PaCO2 > 44 mmHg

• Respiratory alkalosis- PaCO2 < 40 mmHg

• Metabolic acidosis- HCO3 < 25 mEq/L

• Metabolic alkalosis- HCO3 > 25 mEq/L

Case 1

• HCO3 is 8 mEq/L, so there is a metabolic

acidosis

• PaCO2 is 22 mmHg, so there is a

(compensatory) respiratory alkalosis
Anion gap
• AG = Na+ - (Cl- + HCO3-)
– Normal anion gap is 6 +/- 4 mEq/L (up to 10 mEq/L)
– I get worried if the AG is > 20 or rising over 4 hours

• In one study of 57 hospital patients:

– A clear cause of the AG acidosis could be found in only
14% of patients with anion gaps of 17-19 mEq/L
– All patients with anion gaps greater than 30 mEq/L had
lactic acidosis or DKA
Gabow PA et al. NEJM 1980; 303(15):854-8.
Anion gap

• Correct for low albumin

– Albumin is an anion
– For every 10 g/L below normal add 2.5 to the anion
gap

• Adding K+ to the anion gap calculation not

required
Whittier WL, Rutecki GW. Dis Mon 2004;50:117-162
Case 1

• AG = Na+ - (Cl- + HCO3-)

• In this case
AG = 145 - (105 + 8)
= 32
• Patient has an anion gap metabolic acidosis
Anion Gap Acidosis
“CAT MUDPILES”
• C Carbon monoxide, cyanide
• A Alcohol, alcohol ketoacidosis
• T Toluene
• M Metformin, methanol
• U Uremia
• D Diabetic ketoacidosis
• P Phenformin, paracetamol, propylene glycol
• I Iron, isoniazid (INH)
• L Lactic acidosis (numerous causes)
• E Ethylene glycol
• S Salicylates
Anion Gap Without Acidosis

• A patient may have normal pH with a mixed

disorder and occult acidosis

• Low anion gap

– Multiple myeloma
– Lithium intoxication
– Bromide intoxication
Low Anion Gap (< 6)
• Increased unmeasured cations
– hypercalcaemia
– hypermagnesaemia
– lithium intoxication
• Decreased unmeasured anions
– Hypoalbuminaemia
– Dilution
• Artefactual hyperchloraemia
– Bromisim
– Iodism
– Propylene glycol
Check Degree of Compensation

• In metabolic acidemia
– For every 1 mEq/L decrease in HCO3, PaCO2 should
decrease by 1.3 mmHg

• In metabolic alkalemia
– For every 1 mEq/L increase in HCO3, PaCO2 should
increase by 0.6 mmHg
Check Degree of Compensation

• In respiratory acidemia
– For every 10 mmHg increase in PaCO2, HCO3 should
increase 1 mEq/L (acute) or 4 mEq/L (chronic)

• In respiratory alkalemia
– For every 10 mmHg decrease in PaCO2, HCO3 should
decrease 2 mEq/L (acute) or 5 mEq/L (chronic)
Case 1
• In metabolic acidemia
– For every 1 mEq/L decrease in HCO3, PaCO2 should
decrease by 1.3 mmHg
• In this case:
– HCO3 is reduced by 17 from 25 to 8 mEq/L, so PaCO2 should
be decreased by 1.3 x 17, or 22 mmHg, producing a PaCO2 of
18 mmHg
• In actual fact PaCO2 is 22 mmHg, so there is
incomplete compensation, or to put it another way, an
additional respiratory acidosis
Step 5- The ‘Delta Gap’

• There should be a 1:1 relationship between anion

gap and decrease in HCO3
• If they do not correspond a delta gap is said to exist
• Used if:
– If a metabolic disturbance is suspected but not detected
up until this point
– If anion gap and non-anion gap acidosis is suspected to
co-exist
Step 5- The ‘Delta Gap’
• If anion gap is elevated by 10 to 20, then the HCO3
should decrease by 10 from 25 mEq/L to 15 mEq/L

• If HCO3 is actually higher, then a simultaneous

metabolic alkalosis is also present

• If HCO3 is actually lower, then a additional non-

anion gap acidosis is also present
Case 1
• The anion gap is 32, increased by 22
• If there is a 1:1 ratio, the HCO3 should decrease by
22 from 25 mEq/L, to 3 mEq/L

• The HCO3 is actually 8 mEq/L, higher than

anticipated

• There is simultaneous mild metabolic alkalosis

Osmolar gap
• Osmolar gap =
Measured osmolality - calculated osmolality
• Calculated osmolality =
2 x (Na+) + glucose + urea + (ethanol)
(Normal 275-290 mOsm/L)
• Tolerate a gap of up to 10 due to the presence of
unmeasured osmoles such as Ca++, PO4-- and Mg+
+
Case 1

• Calculated osmolality is
(2 x 145) + 4.4 + 7.1 = 301.5

• Actual measured osmolality is 360 mOsm/L

• Osmolar gap = 58.5

Patients with severe acidemia:
A quick rule of thumb

• Does the patient have a serum pH less than 7.10

but look relatively well (CVS stable, near normal
mental status)?
• If so, likely to be one of the following:
– Diabetic ketoacidosis
– Alcoholic ketoacidosis
– Toxic alcohol intoxication (ethylene glycol or
methanol)
Winter’s equation

• Allows for the prediction of the degree of

respiratory compensation in a metabolic
acidosis if the serum bicarbonate is known

• Predicted PaCO2= (HCO3 x 1.5) + 8 (+/- 2)

Narins and Emmitt

• In pure compensated metabolic acidosis the

PaCO2 is the last two digits of the pH

• For example, if the pH is 7.26 the PaCO2 would

be predicted to be 26 mmHg
Metformin

• Metformin causes a lactic acidosis

• Incidence approximately 0.8/100,000 patients
• Associated with age over 65, CCF and renal
insufficiency
• Metformin-induced lactic acidosis associated
with overdose is uncommon
Question
Which of the following may cause an osmolar
gap?
a) Methanol
b) Ethylene glycol
c) Ethanol
d) Isopropyl alcohol
e) a), b) and c)
f) all of the above
Question
Which of the following may cause an anion gap
metabolic acidosis?
a) Methanol
b) Ethylene glycol
c) Ethanol
d) Isopropyl alcohol
e) a), b) and c)
f) all of the above
Methanol
• Methanol is not found in Australian methylated spirits
(ethanol and/or isopropyl alcohol)
• Metabolised to formaldehyde and formic acid, which leads
to life-threatening acidosis
• Intoxicated patient with severe anion gap metabolic
acidosis +/- raised osmolar gap
• Visual changes may be delayed
• Accidental paediatric ingestion may lead to significant
intoxication requiring haemodialysis
Uremia

• Uremia only leads to significant acidosis in

extreme cases (e.g. the patient who has missed
dialysis)
• Thus, in all other cases do not blame uremia for
significant acidosis
Paracetamol
• Massive paracetamol overdose (e.g 4-hour serum
paracetamol level > 800 mg/L) is associated with
early coma and severe metabolic acidosis with
hyperlactataemia
• The pathophysiology is not well understood but it is
not hepatic injury
• N-acetylcysteine therapy within 8-10 hours confers
the same benefits as other patients with ingestions of
lesser magnitude
Iron

• Iron is not an occult ingestion

• Patients with significant iron overdose leading
to acidosis also have:
– Massive GI disturbance
– Cardiovascular instability
Isoniazid (Isonicotinyl hydrazide; INH)

• Isoniazid is an anti-tuberculous agent

• Acute overdose is associated with the rapid
onset of seizures, altered mental status and
metabolic acidosis (hyperlactatemia)
• Both acute overdose and chronic therapy are
associated with alterations in hepatic
transaminases
Isoniazid

• INH alters the metabolism, utilization and

elimination of pyridoxine, a cofactor required for
the production of the neurotransmitter gamma-
amino butyric acid (GABA)

• Thus INH overdose leads to GABA depletion and

seizures that are usually refractory to
conventional therapy
Isoniazid

• Isoniazid-related seizures should be managed

with a combination of benzodiazepines and
pyridoxine (vitamin B6)

• Seizures refractory to benzodiazepines and

barbiturates should prompt the consideration
of INH toxicity
Pyridoxine dosing

• Equal to the amount of INH ingested (gram for

gram)
• If unknown amount of INH ingested:
– 5 g IV
– Repeat doses up to 15 g IV
– Doses greater than 15 g may be neurotoxic (peripheral
neuropathy and transverse mylelitis)
– Problem: 50 mg ampoules in Australia !!!
Lactic acidosis

• Any cause of shock

• CO, cyanide, iron, hydrogen sulfide, salicylates
• Theophylline
• Toluene
• Metformin, phenformin
• Ethylene glycol
Ethylene Glycol

• Pleasant tasting and used in automobile

coolants
• Metabolised to a number of organic acids, most
importantly oxalic acid (calcium oxalate)
• Patient with GI irritation, intoxication, severe
metabolic acidosis, osmolar gap and acute renal
failure
Ethylene Glycol

• Other clues to the diagnosis:

– Worsening acidosis (e.g. pH < 7.20) despite
resuscitation
– Rapidly rising creatinine
– Blood, protein and crystals (oxalic and hippuric
acid)
– Hypocalcemia
Salicylates
• Occult intoxication in the elderly due to repeated
supratherapeutic dosing associated with a high
mortality
• Moderate intoxication associated with a respiratory
alkalosis and alkalemia
• Only terminal salicylism is associated with acidemia,
in which case a double acid-base disorder is seen:
– Metabolic acidosis and respiratory acidosis
Non-anion gap acidosis
• Produced by abnormal bicarbonate loss or abnormal chloride
retention
• Drugs
– Acetazolamide (+ others with carbonic anhydrase activity)
– Cholestyramine
• Acidifying agents (e.g. ammonium chloride)
• GI bicarbonate loss
– Diarrhoea, pancreatic fistula
• Rapid hydration with normal saline
• Abnormal bicarbonate loss
– Renal tubular acidosis, uretoenterostomy
Non-anion gap acidosis- ‘USED CARP’
• U Ureterostomy
• S Small bowel fistula
• E Extra Cl-
• D Diarrhoea
• C Carbonic anhydrase inhibitors
• A Adrenal insufficiency
• R Renal tubular acidosis
• P Pancreatic fistula
Case 2
A young man a history of paraplegia, cystoplasty
and renal impairment presents with altered
mental status and dyspnoea
• pH 7.14 • Na+ 139
• PaCO2 26 • K+ 3.5
• PaO2 116 • Cl- 114
• HCO3 9 • Urinary pH 8.0
• Lactate 0.6
Step 1

• What is the pH (primary acid-base

disturbance)?

• The pH is 7.14
• There is acidemia
Step 2

• Determine whether the primary process is

respiratory, metabolic or both

• The HCO3 is 9, so there is a metabolic acidosis

Step 3

• Calculate the anion gap

• AG = 139 - (114 + 9)
= 16
• There is a mild anion gap
Step 4
• Check the degree of compensation
– The HCO3 is reduced from 25 mEq/L to 9 mEq/L (a
difference of 16), so PaCO2 should be decreased by
1.3 x 16, or 21 mmHg
• PaCO2 should be 19 mmHg, but is in fact 26
mmHg
• There is incomplete compensation, or to put it
another way, an additional respiratory acidosis
Step 5
• Calculate the delta gap

• Anion gap is raised by 6

• HCO3 should be decreased by 6, from 25 mmHg
to 19 mmHg
• HCO3 is in fact much lower at 9 mEq/L, so there
is a large co-existent non-anion gap acidosis
Case 2

• Thus patient has a hypokalemic,

hyperchloremic non-anion gap metabolic
acidosis
• Note the inappropriately high urinary pH (8.0)
• Characteristic of renal tubular acidosis or
uretoenterostomy
Metabolic Alkalosis

• GI acid loss • Administration of bases

– Protracted vomiting or NG – Antacids
suction – Milk -alkali syndrome
• Urinary acid loss – Dialysis
– Diuretics
• Renal bicarbonate
– Cushing’s syndrome
retention
– Adrenogenital syndrome
– Chronic hypercapnia
– Barter’s syndrome
– Hypochloraemia
– Primary
hyperaldosteronism
– Hypokalaemia
– Licorice (glycyrrhizic acid) – Volume contraction.
Respiratory Acidosis

• Acute • Chronic
• Airway obstruction • Lung diseases
• Aspiration • Neuromuscular disorders
• Brochospasm • Obesity
• Drug-induced CNS
depression
• Pulmonary disease
• Hypoventilation of CNS or
muscular origin
Respiratory Alkalosis

• Hypoxia-mediated • Pharmacologic
hyperventilation • Salicylate
• Altitude • Xanthines
• Anaemia • Nicotine
• V/Q mismatch • Sepsis
• CNS-mediated • Pulmonary
hyperventilation • Pneumonia
• Psychogenic • PE
• CVA • CCF
• Increased ICP • Mechanical hyperventilation
Questions?