A 70 year old man was admitted with severe congestive cardiac failure. He has been unwell for about a week and has been vomiting for the previous 5 days. He was on no medication. He was hyperventilating and was very distressed. Admission biochemistry is listed below. He was on high concentration oxygen by mask.
Biochemistry results: Na+ 127, K+ 5.2, Cl- 79, HCO3- 20, urea 50.5, creatinine 0.38 & glucose 9.5 mmols/l. Anion gap 33 mmols/l
Arterial Blood Gases
pCO2 21 mmHg
pO2 154 mmHg
HCO3 19 mmol/l
The history suggests the following possibilities:
The renal failure could be associated with a high anion gap acidosis
Congestive cardiac failure with:
Interestingly, all of these possibilities were suggested by the history.
A co-existing lactic acidosis is not excluded.
A quick perusal of this set of results immediately indicates a significant mixed acid-base disorders. The high anion gap indicates a severe metabolic acidosis is present, but despite this the pH indicates alkalaemia so an even larger alkalosis must be present to have caused this result. Additionally, the severe hypochloraemia is also a powerful alerting signal to the presence of an underlying metabolic alkalosis.
Metabolic acidosis is the only cause of a large anion gap but several other situations may cause a minor elevation in anion gap. An example is large doses of carbenicillin or penicillin which deliver the antibiotic anion as the sodium salt. The antibiotic anion is not measured and this increases the anion gap. The anion gap in the case presented here is large and there is no history suggestive of other factors affecting the anion gap so a severe metabolic acidosis can confidently be diagnosed. The chloride level is quite low and it is always worth checking this result with another specimen.
The diagnosis so far is: a high anion gap metabolic acidosis is present. These are 4 categories of causes for this condition:
A slight stress related increase in blood glucose is noted. Euglycaemic diabetic ketoacidosis is uncommon and is clinically extremely unlikely here. Normal urinary ketone levels should exclude it.
There are two problems to be aware of with ketone testing and these both tend to give false negative results: the reagent strip may be outdated and give a false negative result, or a coexistent lactic acidosis may be present. A lactic acidosis alters the beta-hydroxybutyrate to acetoacetate ratio and acetoacetate levels will fall. The ‘Ketostix’ brand nitroprusside test detects acetoacetate only and may give a false negative result for ‘ketones’ in this situation. There is no note of the detection of the odour of ketones being detected about the patient. Conclusion is that there is no evidence of ketoacidosis.
Toxin ingestions (eg methanol, ethylene glycol, salicylates, paraldehyde) which cause acidosis are excluded on the history so far. Any history of alcoholism or if the patient appears intoxicated should prompt re-consideration of this diagnosis.
The renal failure present in this case is sufficient to cause a metabolic acidosis.
Impaired muscle tissue perfusion (due to the heart failure and the fluid loss from the vomiting) will cause a lactic acidosis and this should be considered here. A lactate level will quickly assess this possibility. Prerenal acute renal failure can cause a metabolic acidosis by two mechanisms: tissue hypoperfusion (lactic acidosis) and retention of acid anions (acidosis of acute renal failure).
The diagnosis so far: High anion gap metabolic acidosis due to acute prerenal renal failure and probably a coexistent lactic acidosis.
The [HCO3] is inappropriately high for the rise in the anion gap. The anion gap reported here was calculated using the formula which includes potassium, so 17 mmols/l can be taken as its upper reference limit. The anion gap is 16 mmol/l higher than this upper limit but the [HCO3] is only 5 mmol/l lower than its reference value of 24 mmol/l.
The delta ratio is high (3.2) so lets consider the two possibilities that are consistent by this and consider how they may be distinguished:
First possibility for a high delta ratio: A coexisting metabolic alkalosis is present. Assessment: The history is consistent with this as severe vomiting is present and this is an important cause of metabolic alkalosis.
Second possibility: The patient has a pre-existing chronic respiratory acidosis with renal retention of bicarbonate. For example, if the patient had a chronic hypercapnia with pCO2 of 60 mmHg, renal compensation would raise the [HCO3] to 32 mmols/l (based on the ‘4 for 10 rule’). A bicarbonate level of 19 could represent a fall from 32 mmols/l: a decrement of 13 mmols/l (in this hypothetical example). If this hypothesis is correct, then there may be no metabolic alkalosis.
What evidence can be found of a recent or long-standing chronic respiratory acidosis? In this case, there is no history of chronic respiratory disease. CO2 retention requires severe lung disease. Current pCO2 is low so the patient is obviously able to hyperventilate enough to drop his pCO2 despite the presence of congestive heart failure! Other useful checks are:
Our assessment is that there is no evidence of chronic respiratory acidosis in this patient.
Conclusion then is that a metabolic alkalosis is present. The majority of causes of metabolic alkalosis are due to diuretic use or loss of acidic gastric juice (vomiting or NG suction). A history of five days of vomiting is the cause here. Diuretic use has been excluded on history.
The rise in the anion gap is normally larger than the fall in bicarbonate because at least half of the buffering for metabolic acid-base disorders occurs intracellularly (minimising the decrement in plasma [HCO3]) but the acid anions remain extracellularly and contribute as excess unmeasured anions to the anion gap.
Diagnosis so far is:
There is still a problem in the analysis of this case so far because although there is a significant net alkalaemia (indicating the metabolic alkalosis is more severe then the metabolic acidosis), the [HCO3] is reduced rather then elevated! Consequently, a third primary acid-base disorder must be present and adding to the net alkalaemia - that is, there must be a respiratory alkalosis. To approach this using the compensation rules:
Is the respiratory compensation appropriate?
As the [HCO3] is less then 24 mmol/l, rule 5 for a metabolic acidosis (rather than rule 6) is best to assess this. The predicted pCO2 is about 36 mmHg. As the actual pCO2 is much lower than this, the third primary acid-base disorder is a respiratory alkalosis. This is secondary to the heart failure and the hyperventilation stimulated by the dyspnoea. Any condition which decreases lung compliance will cause dyspnoea. If the pulmonary oedema was more severe then a respiratory acidosis would be a likely outcome.
This patient has a triple acid-base disorder:
The pO2 is elevated due to administration of a high inspired oxygen concentration.
In complicated cases like this it is very important to check results to avoid errors.
For example, in this case if the [Cl-] was really 99 instead of 79mmol/l, then the anion gap would not be elevated. This could be a simple error and such is possible is results are passed on to you after being written down by somewone else after a phone report from the laboratory. It is best to work from a hard-copy printout. If the results are surprising and especially if inconsistent with the clinical picture then double check all results. Many blood gas machines now measure a selection of electrolytes so compare the results on the blood gas printout with those from the electrolyte results from biochemistry on the same patient. In this particular case, the chloride result should be checked.
Similarly check that the blood gas results are internally consistent (ie put the results in the Henderson-Hasselbalch equation and check they are correct). Results taken over the phone by an intermediary can be written incorrectly. Printed results are generally reliable but of course they may still be in error because of faults with collection and handling of the blood gas sample prior to analysis.