acid-base

Western Australian Toxicology Service

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

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

• PaCO2 22 mmHg

• PaO2 95 mmHg

• HCO3 8 mEq/L

• Osmolality 360 mOsm/L

• Na+ 145 mEq/L

• K+ 2.7 mEq/L

• Cl- 105 mEq/L

• Urea 7.1 mmol/L

• Cr 88 mcmol/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

requiredWhittier 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 2A young man a history of paraplegia, cystoplasty and renal impairment presents with altered mental status and dyspnoea

• pH 7.14

• PaCO2 26

• PaO2 116

• HCO3 9

• Lactate 0.6

• Na+ 139

• K+ 3.5

• Cl- 114

• Urinary pH 8.0

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– Protracted vomiting or NG

suction

• Urinary acid loss– Diuretics

– Cushing’s syndrome

– Adrenogenital syndrome

– Barter’s syndrome

– Primary hyperaldosteronism

– Licorice (glycyrrhizic acid)

• Administration of bases– Antacids

– Milk -alkali syndrome

– Dialysis

• Renal bicarbonate retention– Chronic hypercapnia

– Hypochloraemia

– Hypokalaemia

– Volume contraction.

Respiratory Acidosis

• Acute

• Airway obstruction

• Aspiration

• Brochospasm

• Drug-induced CNS

depression

• Pulmonary disease

• Hypoventilation of CNS or

muscular origin

• Chronic

• Lung diseases

• Neuromuscular disorders

• Obesity

Respiratory Alkalosis

• Hypoxia-mediated

hyperventilation

• Altitude

• Anaemia

• V/Q mismatch

• CNS-mediated

hyperventilation

• Psychogenic

• CVA

• Increased ICP

• Pharmacologic• Salicylate

• Xanthines

• Nicotine

• Sepsis

• Pulmonary• Pneumonia

• PE

• CCF

• Mechanical hyperventilation

Questions?