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Question 12 - 2002, Paper 2

Outline the causes, and the principles of management of lactic acidosis in the critically ill.

College Answer

•    Causes can be divided into increased lactate production (including enhanced pyruvate production, reduced pyruvate conversion to CO2 & water or glucose, or preferential conversion of pyruvate to lactate), and diminished lactate utilisation.
•    Most causes in the critically ill are due to the many causes of tissue hypoperfusion [Type A] (resulting in increased production and decreased utilisation), or decreased utilisation due to liver disease (especially with use of lactate containing fluids in renal replacement therapy). Other common causes include seizures, beta-2 adrenergic agonists (eg. adrenaline and salbutamol), metformin (uncertain mechanism) and post-cardiac surgery. Consider also d- lactic acidosis associated with the short bowel syndrome.
•    Principles of management include correcting hypoperfusion (fluids, inotropes, vasopressors), and if possible, correction of underlying disorder (treat seizures, shivering, glucose abnormalities, etc.) and removal of offending drugs (including metformin, adrenaline, renal replacement fluid).

Discussion

Causes of lactic acidosis  are discussed at length in another chapter.

In brief, one may classify it according to several classification systems, of which the Cohen-Woods classification is for some reason the more popular.

The Cohen-Woods classification is as follows:

  • Type A (lactic acidosis due to impaired tissue perfusion)
  • Type B (lactic acidosis with adequate tissue perfusion).
    • Type B1 (lactic acidosis a result of “disease states”)
    • Type B2 (drug-related)
    • Type B3 ( the consequence of inborn errors of metabolism)

Causes of lactic acidosis can be better classified according to the lesser-known (but biochemically superior) Phuypers and Pierce system:

A Mechanism-based Classification of Lactic Acidosis

Increased rate of glycolysis due to lack of ATP

  • Shock: circulatory collapse or regional ischaemia
  • Lactic acidosis due to severe hypoxia
  • Lactic acidosis due to severe anaemia
  • Carbon monoxide poisoning and tissue hypoxia
  • Regional hypoxia and microvascular shunting in sepsis

Increased rate of glycolysis due to exogenous pro-glycolytic stimulus

  • Beta-2 adrenoceptor agonists: salbutamol, adrenaline, isoprenaline  
  • Catecholamine excess in hypovolemic shock
  • Lactic acidosis due to excess glycolysis in malignancy

Unregulated substrate entry into glycolysis

  • Xylitol, sorbitol, fructose infusions

Pyruvate dehydrogenase inactivity

  • Thiamine deficiency as a cause of lactic acidosis
  • Inhibition of pyruvate dehydrogenase in sepsis
  • Lactic acidosis due to inborn errors of metabolism

Defects of oxidative phosphorylation

  • Cyanide (and by extension nitroprusside) toxicity
  • Paracetamol toxicity
  • Salicylate toxicity
  • Lactic acidosis due to inborn errors of metabolism
  • Metformin
  • Propofol
  • Isoniazid
  • The toxic alcohols - ethanol, methanol and ethylene glycol
  • NRTIs (nucleoside reverse transcriptase inhibitors)

Decreased lactate clearance

  • Lactic acidosis due to impaired hepatic or renal function
  • Decreased gluconeogenesis due to the ethanol and methanol
  • Decreased gluconeogenesis due to ketoacidosis

The approach to the management of lactic acidosis can be divided into two main approaches:

  • Manage the underlying cause of the lactic acidosis - and the precise management strategy obviously depends on the aetiology
  • Increase the clearance of lactate artificially using CVVHDF (which is probably not a very effective strategy, and represents immature "lactate-centric" management).

References

Narins RG, Krishna GG, Yee J, Idemiyashiro D, Schmidt RJ: The metabolic acidoses. In: Maxwell & Kleeman's Clinical Disorders of Fluid and Electrolyte Metabolism, edited by Narins RG, New York, McGraw-Hill, 1994, pp769 -825

 

Luft FC. Lactic acidosis update for critical care clinicians. J Am Soc Nephrol 2001 Feb; 12 Suppl 17 S15-9.

 

Ohs manual – Chapter 15 by D J (Jamie) Cooper and Alistair D Nichol, titled “Lactic acidosis” (pp. 145)

 

Cohen RD, Woods HF. Lactic acidosis revisited. Diabetes 1983; 32: 181–91.

 

Reichard, George A., et al. "Quantitative estimation of the Cori cycle in the human." Journal of Biological Chemistry 238.2 (1963): 495-501.

 

Andres, Reubin, Gordon Cader, and Kenneth L. Zierler. "The quantitatively minor role of carbohydrate in oxidative metabolism by skeletal muscle in intact man in the basal state. Measurements of oxygen and glucose uptake and carbon dioxide and lactate production in the forearm." Journal of Clinical Investigation 35.6 (1956): 671.

 

Phypers, Barrie, and JM Tom Pierce. "Lactate physiology in health and disease." Continuing Education in Anaesthesia, Critical Care & Pain 6.3 (2006): 128-132.

 

Question 14 - 2003, Paper 2

Outline the way in which you would evaluate the aetiology of metabolic acidosis in the critically ill.

College Answer

A metabolic acidosis is a process which, if uncorrected, would lead to an acidaemia.  It is usually associated with a low bicarbonate concentration (or total CO2), but an acidosis may be masked by a co-existing metabolic alkalosis.  A simple classification is to categorise acidosis into accumulation of acids (measured, i.e. chloride [hyperchloraemic metabolic acidosis] or unmeasured [increased anion gap metabolic acidosis]), or renal or gastrointestinal loss of bicarbonate (with absorption of chloride, resulting in hyperchloraemic metabolic acidosis). The anion gap (Na + K – Cl – HCO3) is usually determined primarily by negatively charged plasma proteins and has a range of approximately 10 to 16 mmol/L.  This will be decreased by about 2.5 mmol/L for every decrease inalbumin by 10 g/L.  An increased anion gap (which can occur in the absence of a low bicarbonate concentration) may be due to a fall in unmeasured cations (Ca, Mg), or more commonly to the presence of unmeasured anions (e.g. lactate [d- or l-], ketoacids, formate [methanol], glycolate and oxalate [ethylene glycol].  Some of these can be specifically measured.  Calculation of an osmolar gap may also help as a screening test for methanol or ethylene glycol intoxication once alcohol has been excluded (calculated osmolality = 2*Na + Glucose + Urea + ethanol/4.6).   Urinary pH (inappropriately alkaline for an acidaemia) and electrolytes may facilitate eliciting the specific cause of the renal bicarbonate loss (e.g. renal tubular acidosis).

Discussion

The college answer - I assume - outlines in prose the features which the examiners would have been looking for. The answer, in my opinion, calls for a systematic and structural response. The candidate ought to demonstrate that their approach to the evaluation of metabolic acidosis is not a disorganised bafflement of various physiological principles and biochemical tests.

Thus:

  • Calculate the anion gap
    • (Na+ + K+) - (Cl- + HCO3-)
    • The anion gap achieves a diagnostic classification of metabolic acidosis
    • A raised anion gap identifies unmeasured anions (eg. lactate, ketones, metabolic byproducts of toxic alcohols) as potential causes of the acidosis
    • A normal anion gap identifies changes in chloride and bicarbonate as causes of the metabolic acidosis
  • Calculate the delta ratio
    • (change in antion gap) / (change in bicarbonate)
    • The delta ratio quantifies the contribution to the acidosis of unmeasured anions and the chloride-bicarbonate balance
    • This way, mixed acid-base disorders may be revealed
  • For normal anion gap metabolic acidosis, measure urinary electrolytes and calculate the urinary anion gap
    • Urinary anion gap can be used to differentiate between gastrointestinal and renal causes for the normal anion gap metabolic acidosis.
    • A high urinary anion gap suggests that there is a renal cause for the acidosis (i.e. that chloride and ammonium excretion is inappropriately low)
    • A low or negative urinary anion gap suggests that there is an appropriate attempt to excrete chloride and ammonium, and that the cause of acidosis is extrarenal.
  • For high anion gap metabolic acidosis, measure the serum osmolality and calculate the osmolar gap
    • The osmolar gap will reveal whether there are osmotically active substances in the bloodstream which are not measured as a part of the normal bicohemistry. These may be responsible for the raised anion gap metabolic acidosis.
    • The osmolar gap may narrow the list of differentials

Given that one cannot predict the opinions of the examiners regarding Stewart's physicochemical approach to acid-base disorders, in an answer like this one, the candidate should probably give it a miss.

References

Kraut, Jeffrey A., and Nicolaos E. Madias. "Metabolic acidosis: pathophysiology, diagnosis and management." Nature Reviews Nephrology 6.5 (2010): 274-285.

 

Fencl, Vladimir, et al. "Diagnosis of metabolic acid–base disturbances in critically ill patients." American journal of respiratory and critical care medicine162.6 (2000): 2246-2251.

 

Moviat, M. A. M., F. M. P. Van Haren, and J. G. Van Der Hoeven. "Conventional or physicochemical approach in intensive care unit patients with metabolic acidosis." Critical Care 7.3 (2003): R41.

 

Park, M., et al. "Clinical utility of standard base excess in the diagnosis and interpretation of metabolic acidosis in critically ill patients." Brazilian Journal of Medical and Biological Research 41.3 (2008): 241-249.

Question 7 - 2004, Paper 2

Outline the way in which you would evaluate the aetiology of metabolic alkalosis in the critically ill.

College Answer

Evaluation of causes of metabolic alkalosis requires a systematic approach involving history, examination and some specific investigations. Categories of aetiology include loss
of hydrogen ions (gastrointestinal, renal), intracellular shift of hydrogen ions, administration of alkali, and contraction alkalosis. History and examination will reveal, documented fluid losses (vomiting & gastric losses, laxative induced diarrhoea), volume depletion (loss of bicarbonate free fluids), administered drugs (mineralocorticoids, diuretics, and antacids in renal failure), alkali (bicarbonate, lactate, citrate etc) and recent hypercapnia. Investigations may reveal hypokalemia (with hydrogen shifting into cells), hypochloremia and urinary findings may include excessive potassium excretion (reabsorbing hydrogen), alkaline pH (increased bicarbonate) and inappropriately elevated chloride excretion (diuretic therapy, hypokalaemia).

Discussion

This question closely resembles Question 7  from the first paper of 2008.

References

Question 17 - 2005, Paper 1

Outline   your   approach   to  determining   the   appropriate   magnitude   of  respiratory compensation for a metabolic acidosis and a metabolic alkalosis.

College Answer

The  extent of  respiratory compensation for  a  metabolic disorder is  determined by the balance between the abnormality in the pH (hence the drive to change), and how hard it is to get  there  (eg.  work  of  respiratory muscles in  hyperventilation).   A  knowledge of  the expected degree of compensation for a given acid base status is necessary to determine the presence of an additional respiratory disorder.  Two traditional methods have been used: use of formulae, and the use of a standardized diagram.

The direction of change in the CO2 should be to normalise the pH for the underlying disorder.  A normal pH indicates an additional process is present.  The commonest relevant formulae to estimate the PaCO2 in use are:

For a metabolic acidosis, the expected PaCO2 = the last two digits of the pH (+/- 2-5 mmHg; from pH 7.1 to 7.6; Narins 1980), or the expected PaCO2 = (1.5 X measured bicarbonate) + 8 (+/- 2).  The measured bicarbonate, not the standard bicarbonate, must be used.   Other approachs include: expected change in PaCO2 = Standard Base Excess (Schlichtig R et al Crit Care Med 1998); 1.2 mmHg fall in PaCO2 for each 1 mmol/L reduction in HCO3.

For a metabolic alkalosis, the same equation is used, though the reliability may be less than with a metabolic acidosis.  Expected PaCO2 = the last two digits of the pH (+/- 2-5; from pH 7.1 to 7.6). Other approachs: change in PaCO2 = 0.6 X Standard Base Excess (Schlichtig R et al Crit Care Med 1998); 0.7 mmHg rise in PaCO2 for each 1 mmol/L increase in HCO3.

Discussion

This question regards the routine bedside tests for adequacy of compensation.

Specifically it is the magnitude of change of CO2 in response to the changes in pH.

One recalls several rules. None are especially precise. This whole issue is discussed at great length in the chapter on the assessment of compensation by the Boston and Copenhagen methods.

However, this question specifically asks for Winter's Rule:

1) In metabolic acidosis, PCO2 = (1.5 x HCO3) + 8 ... within a range of plus-minus 2mmHg

2) In metabolic alkalosis, PCO2 = (0.7 x HCO3) + 20 ... within a range of plus-minus 5mmHg

References

 

Roberts, Kathleen E., et al. "Evaluation of respiratory compensation in metabolic alkalosis." Journal of Clinical Investigation 35.2 (1956): 261.

 

 

Question 10 - 2005, Paper 2

Following cardiopulmonary resuscitation for severe asthma  in a 6 year old child the following blood gas results are obtained  (she remains unconscious, paralysed and mechanically ventilated).

Barometric pressure = 760 mmHg

FiO2

0.5

pH

6.65

7.35-7.45

pCO2

212

35-45 mmHg

pO2

90

mmHg

HCO3

23

20-30 mmol/L

Lactate

12

<2 mmol/L

Please explain these results and outline what action you will take.

College Answer

Severe acidemia due to a mixed severe respiratory and metabolic (lactate) acidosis. Apparently adequate oxygenation (very low A-a gradient). The elevation in lactate may have been due to tissue hypoxia but the PaO2 at present might appear adequate. She is likely to have received intravenous adrenaline and possibly salbutamol, both can cause lactic acidosis (due to inhibition of pyruvate dehydrogenase (Day NP et al Lancet 1996;348:219-223) and possibly other effects on glycolytic enzymes, accelerating glycolysis).
Measures to increase alveolar ventilation are urgently required. Evaluation of airway, breathing and circulation (ABC) is the first response. Urgent chest auscultation and observation should be performed. Capnography (+/- laryngoscopy) should be used to confirm intra-tracheal position of ETT. To achieve a PO2 of 90 with almost zero A-a gradient, the tube must be in the trachea; for the same reason, endobronchial intubation is unlikely but should be excluded. Consider pneumothorax
– as this might compromise alveolar ventilation. Any leak should be identified (if the endotracheal tube is un-cuffed it could be replaced with a larger tube or a cuffed tube). Check to make sure the ventilator tubing is not leaking/unattached. The tidal volume and respiratory rate must be checked together with the peak pressure limit (if the patient is being ventilated with a mechanical ventilator). The chest excursion should be observed to ensure that there is a rise during inhalation. If excursion appears inadequate it is appropriate to try an increase in the volume or pressure and observe
whether the ventilation improved. The extent of gas trapping needs to be evaluated. If there is significant gas trapping then a reduction of respiratory rate is required (to prolong the expiratory time), however given the current PaCO2 this may require an increase in tidal volume. An alternative strategy would be to plan for regular 30 second disconnections every 5 minutes or so (particularly if there was associated hypotension).

Discussion

This is not a pure ABG interpretation question; it required some thinking about the management of severe asthma.

But first, lets interpret the ABG.

  1. The A-a gradient is normal:
    (0.5 x 713) - (212 x 1.25) = 91.5
    Thus, A-a = (91.5 -90) = 1.5mmHg
  2. There is acidaemia
  3. The PaCO2 is contributing to the acidosis
  4. The SBE is not given, but the bicarbonate is normal, suggesting that there is either no metabolic acidosis, or that the metabolic acidosis coexists with a metabolic alkalosis. The presence of a raised lactate (12mmol/L) suggests that the latter is correct. 
  5. This question gives a history of asthma and cardiac arrest which suggests that the respiratory acidosis is acute. The expected HCO3- in this setting would be 41.2:
    bicarbonate compensation = (212-40)/10 multiplied by 1 = 17.2 mmol/L
    Thus, there is also a metabolic acidosis present here.

The lactate can be left to its own devices. Given that you would be using vast amounts of salbutamol here, it can be expected to persist for some time.

The PaCO2 requires immediate attention.

The ventilation strategies in status asthmaticus are discussed elsewhere.

A systematic approach would resemble the following:

Airway:

  • Ensure the ETT is not kinked or blocked with secretions, and is of a satisfactory internal diameter

Breathing:

  • Assess the expiratory flow using ventilator waveforms and capnometry
  • Adjust the I:E ratio to allow for prolonged expiration
  • Adjust the repiratory rate to allow for prolonged expiration
  • Consider using a low PEEP.

Circulation

  • Assess the extent of dynamic hyperinflation
  • Assess intravascular volume and aim for a higher CVP, to counteract the preload-limiting effects of dynamic hyperinflation
  • Consider regular disconnections of the ETT, and/or manual decompression

References

Oh's Intensive Care manual: Chapter 35   (pp. 401) Acute  severe  asthma by David  V  Tuxen  and  Matthew  T  Naughton.

 

 

Question 11 - 2005, Paper 2

A  45  year old  man  is  admitted unconscious  to  the  Emergency  Department.                      

   His electrolytes are as follows:

Sodium

119

132-144 mmol/L

Potassium

5.5

3.1-4.8 mmol/L

Chloride

80

93-108 mmol/L

Bicarbonate

<5

20-30 mmol/L

Urea

10

3.0-8.0 mmol/L

Creatinine

105

60-120 micromol/L

Glucose

13

3.0-5.5 mmol/L

Lactate

8.8

<2 mmol/L

Measured osmolality

340

275-295 mOsm/kg

Urine ketones

negative

Please interpret these results.  Outline a differential diagnosis based on the biochemical findings and indicate how you will exclude each.

College Answer

Results demonstrate an increased anion gap metabolic acidosis with mild hyperglycaemia and hyperosmolar hyponatraemia. The marked anion gap (39.5) is not solely explained by the lactate level, and ketones or renal failure are not present. There is also a large osmolar gap (calculated osmolality = 340 –261=81), which suggests an additional agent/toxin is causing acidosis and having osmotic effect.
Differential diagnosis includes:
•    Methanol: History (“hootch” consumption); measurement of methanol and formate levels often takes time, but negative ethanol may be useful. The lack of renal dysfunction does not exclude methanol.
•    Ethylene glycol: History (?suicidal intent), plasma ionised calcium, oxalate crystalluria, Woods lamp examination for fluorescence; unlikely given normal renal function
•    Alcoholic ketoacidosis: measure ethanol and plasma beta- hydroxybutyrate. Negative urinary ketones (acetoacetate) might reflect a low redox state, with most of the keto-anion being in the form of beta-hydroxybutyrate, and with a huge amount of acetone and glycerol (plus some ethyl alcohol) causing the osmolar gap. The enormous anion gap would then be a mixture of lactate, beta-hydroxybutyrate and some acetate from ethanol metabolism.
•    Pyroglutamic acidosis: History of paracetamol ingestion in the face of liver dysfunction.
Measure pyrogluamic acid levels. Less likely as large osmolar gap.
•    Salicylic acid: History (?suicidal intent), measure salicylate levels, may have respiratory alkalosis. Less likely as large osmolar gap.
Hypoadrenalism could be considered (hyponatraemia, hyperkalaemia, metabolic acidosis), but on its own does not explain the osmolar gap and the non-lactate component of the anion gap.
DKA is on the differential, but the osmolar gap (acetone, glycerol) is higher than it usually gets, unconsciousness is not normally a feature and needs to be explained separately, and the lactate is unusually high.
Factitious causes of hyponatraemia (hyperlipidaemia etc) might have been mentioned. However, although they will artefactually raise the osmolar gap, they do not increase the anion gap, and they don’t cause acidosis or unconsciousness.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated
  2. There is no pH reported
  3. The PaCO2 is not reported
  4. The SBE is not reported, but the bicabonate is less than 5mmol/L, suggesting a severe metabolic acidosis
  5. The respiratory compensation cannot be assessed
  6. The anion gap is (119) - (80 + 5) = 34, or 39.5 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (34 - 12) / (24 - 5) = 1.15. This delta ratio suggests that there is a pure high anion gap metabolic acidosis here.
  7. The osmolar gap is raised:
    340 - [ (2 × 119) + 13 + 10] = 79

The lactate cannot account for this increase in anion gap, much less the increase in osmolar gap.

Differential diagnoses of a raised osmolar gap in metabolic acidosis include the following:

References

Kraut, Jeffrey A., and Ira Kurtz. "Toxic alcohol ingestions: clinical features, diagnosis, and management." Clinical Journal of the American Society of Nephrology 3.1 (2008): 208-225.

Question 10 - 2006, Paper 1

A 75 year old woman with a reduced level of consciousness is intubated and ventilated after a single grand mal convulsion.  Indicate  the pathophysiologic  disturbances revealed by the following blood gas and electrolyte profile, taken 10 minutes post intubation. Outline how this information should influence her management.

Normal values

Barometric pressure

760mm Hg

FiO2

1.0

pH

7.05

7.35-7.45

pO2

280mm Hg

pCO2

43mm Hg

35-45

HCO3-

11.5mmol/L

21-30

Standard base excess

-16.8mmol/L

Sodium

128mmol/L

135 -145

Potassium

3.1mmol/L

3.2 - 4.5

Chloride

82mmol/L

100 -110

Urea

22.0mmol/L

3.0 - 8.0

Creatinine

0.12mmol/L

0.07 - 0.12

Glucose

79.0mmol/L

3.0 - 7.8

Lactate

9.2mmol/L

0.5 - 2.0

College Answer

Candidates were expected to outline each of the important abnormalities and how they should influence her management. One approach would be the following:

•    The biochemistry supports a diagnosis of hyperosmolar hyperglycaemic syndrome, with post-ictal lactic acidosis. There is also a likely component of ketoacidosis.

•    The high urea / creatinine ratio confirms significant dehydration – most people with this condition are at least 10% dehydrated by body weight – usually more. She will require steady rehydration over 12 to 24 hours.

•    The sodium adjusted to normoglycaemia is about 153 mmol/L. This means that, after intravascular volume is restored with isotonic fluids, rehydration should be conducted with relatively hypotonic fluids eg 0.45% saline initially.

•    The metabolic acidosis is uncompensated. The minute ventilation should be increased (if this can be done safely), to replicate appropriate respiratory compensation.

•    There is a raised anion gap (34.5 mEq/L without K). The degree of lactate elevation is insufficient to explain the anion gap, indicating probable co-existing ketoacidosis. Beta- hydroxybutyrate should therefore be measured. An insulin infusion (0.1 U/kg/hr) is required for gentle glucose correction and reversal of ketoacidosis.

•    The plasma potassium is already reduced, indicating a severe deficit and the need for immediate replacement in the absence of anuria. She is likely to need 10 - 20 mmol/hr or more for many hours, since the total deficit will exceed 6 mmol/kg.

•    Blood gases, Na, K and glucose will need frequent (hourly) measurement initially. Rapid reductions in osmolality should be avoided (using sodium adjusted to normoglycaemia as a surrogate).

The A-a gradient is significantly elevated at 380 mm Hg. This could indicate aspiration pneumonitis, pneumonia, or segmental collapse – even endobronchial intubation. These possibilities should be looked for clinically and on CXR.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high:
    PAO2 = (713) - (43 × 1.25) = 659.25
    Thus, A-a = ( 659.25 - 280) = 379.25mmHg.
  2. There is acidaemia
  3. The PaCO2 is not compensatory
  4. The SBE is -16.8, suggesting a severe metabolic acidosis
  5. The respiratory compensation is inadequate - the expected PaCO2(11.5 × 1.5) + 8 = 25.25mmHg, and thus there is also a respiratory acidosis
  6. The anion gap is (128) - (82 + 11.5) = 34.5, or 37.6 when calculated with potassium.
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (34.5 - 12) / (24 - 11.5) = 1.8. 
    This delta ratio suggests that there is a pure high anion gap metabolic acidosis here, with perhaps just a hint of pre-existing metabolic alkalosis.
     

The lactate is 9.2, which does not account for much of the anion gap, suggesting that other unmeasured anions are present.

If one were to ignore the HONK, one would leave it at that.

However, most people would notice that the glucose is 79.

This is slightly abnormal. And it influences the sodium value.

The corrected sodium is 128 + (glucose/4), or 147.8 mmol/L.

Because the college do not show their working, it is impossible to say how they managed to get a sodium value of 153. If one were to use the standard formula, one gets 147.75mmol/L.

One may also use a slightly less standard formula, where for every 5.6mmol/L of glucose, the sodium decreases by 1.6mmol/L for the first 25mmol of glucose, and by 2.4mmol/L for hyperglycaemia above 25mmol/L. In such a case, the corrected sodium is 158:

= measured Na+ plus (25 / 5.6) × 1.6, plus [(79-25)/5.6]× 2.4

In any case, there is hypernatremia.

Anyway. The college question asks how any of this information would influence your management.

I will go through the abnormalities systematically.

  • Acidosis
    • This is a combination of several contributing aetiologies:
      • uremic acidosis
      • post-ictal lactic acidosis
      • ketoacidosis
      • respiratory acidosis
    • The ketoacidosis should be confirmed with a blood ketone (hydroxybutyrate) level.
    • Management would consist of the following meaasures:
      • careful rehydration
      • insulin therapy (the college recommends 0.1 unit/kg/hr)
      • increased minute ventilation
  • Hypokalemia
    • According to HONK literature, the total deficit will likely exceed 5-15mmol/kg. Aggressive replacement is in order.
  • A-a gradient
    • For whatever reason, this patient is relatively hypoxic.
    • This should be investigated clinically, and with a CXR.

References

Hyperglycemic Comas by P. VERNON VAN HEERDEN from Vincent, Jean-Louis, et al. Textbook of Critical Care: Expert Consult Premium. Elsevier Health Sciences, 2011.

 

Oh's Intensive Care manual: Chapter 58  (pp. 629) Diabetic  emergencies  by Richard  Keays

 

Umpierrez, Guillermo E., Mary Beth Murphy, and Abbas E. Kitabchi. "Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome." Diabetes Spectrum15.1 (2002): 28-36.

 

ARIEFF, ALLEN I., and HUGH J. CARROLL. "Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of theraphy in 37 cases." Medicine 51.2 (1972): 73-94.

 

Gerich, John E., Malcolm M. Martin, and Lillian Recant. "Clinical and metabolic characteristics of hyperosmolar nonketotic coma." Diabetes 20.4 (1971): 228-238.

 

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes." Diabetes care 32.7 (2009): 1335-1343.

 

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes a consensus statement from the American Diabetes Association." Diabetes care 29.12 (2006): 2739-2748.

 

Ellis, E. N. "Concepts of fluid therapy in diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma." Pediatric clinics of North America 37.2 (1990): 313-321.

 

Pinies, J. A., et al. "Course and prognosis of 132 patients with diabetic non ketotic hyperosmolar state." Diabete & metabolisme 20.1 (1993): 43-48.

Question 4 - 2006, Paper 2

The following arterial blood gas and biochemistry results are from a patient  with chronic cardiac and respiratory disease and recent profuse vomiting.

FiO2   0.4  
pH   7.5  
PaO2                     58.0 mmHg  
PaCO2                  47.0mmHg  
HCO3-                 34.8 mmol/L (22 - 27)
BE 10.2 mmol/L   (-2.0 to +2.0)
Na+ 137mmol/L (135 - 145)
K+ 2.5mmol/L (3.5 - 5.0)
Cl-             92mmol/L   (95 - 105)

a)  Describe the acid-base and the metabolic disturbance.

b)  List the potential causes of these abnormalities in this patient.

c)  Outline the management of the metabolic and acid-base disturbance

College Answer

The major abnormalities are:

a)  Metabolic alkalosis with respiratory compensation

b)  Hypokalemia and hypochloremia

c)  Normal anion gap

d)  An increased apparent strong ion difference [(Na + K) – Cl] = 47

Possible causes in this patient include

a)  Diuretic therapy

b)  Steroid therapy

c)  Vomiting from gastric outlet obstruction

d)  Post hypercapnic alkalosis

Outline the management of the metabolic and acid-base disturbance.

1) Normal saline administration

2) K supplements

3) Acetazolamide

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high:
    PAO2 = (0.4 × 713) - (47 × 1.25) = 226.45
    Thus, A-a = ( 226.45 - 58) = 168.mmHg.
    But you did not need to know the A-a gradient to recognise that the patient is hypoxic.
  2. There is alkalaemia
  3. The PaCO2 is compensatory
  4. The SBE is 10.2, suggesting a metabolic alkalosis
  5. The respiratory compensation is adequate - the expected PaCO2( 0.7 × 34.8) + 20 = 44.4mmHg, and this falls within the +/- 5mmHg error range of this blood gas rule. If we were to use the Copenhagen rules, the expected PaCO2 would be around 50mmHg (40+ SBE).

Thus, this is a reasonably well compensated metabolic alkalosis.

There is also hypochloraemia and hypokalaemia.

The patient has chronic cardiac and respiratory disease, and has been vomiting.

Thus, the broad list of potential causes of metabolic alkalosis can be narrowed to the following:

  • Diuretics (for CCF)
  • Corticosteroids (for COPD)
  • Gastric secretion loss though vomiting
  • β-lactam use (for exacerbation of COPD)
  • Post-hypercapneic alkalosis is possible, but less likely (because this metabolic alkalosis is well-compensated, and with post-hypercapneic alkalosis the respiratory compensation is by definition inadequate, i.e. the calculated "expected" PaCO2 should be higher than the measured PaCO2)

The college then go on to suggest three uninspired management options. For instance, they want to replace potassium, which is a sensible reaction to a low potassium, but not an elegant solution to any underlying problem. Similarly, acetazolamide and sodium chloride may seem essentially cosmetic measures, as they only serve to improve the appearance of the blood gas. 

Management of metabolic alkalosis is discussed in greater detail elsewhere. Most of the detail can be found in the following literature sources:

In brief:

  • Address the underlying problem:
    • Stop the diuretics, treat the hyperaldosteronism, etc etc.
  • Correct volume depletion - ideally with normal saline
  • Correct hypokalemia - ideally with potassium chloride
  • Alternative strategies if the patient is fluid-overloaded:
    • Acetazolamide
    • Hydrochloric acid (HCl)
    • Infusions of cationic amino acids such as lysine and arginine
    • Correction of hypoalbuminaemia

References

Tripathy, Swagata. "Extreme metabolic alkalosis in intensive care." Indian journal of critical care medicine: peer-reviewed, official publication of Indian Society of Critical Care Medicine 13.4 (2009): 217.

 

Galla, John H. "Metabolic alkalosis." Journal of the American Society of Nephrology 11.2 (2000): 369-375.

 

Pahari, D. K., et al. "Diagnosis and management of metabolic alkalosis."JOURNAL-INDIAN MEDICAL ASSOCIATION 104.11 (2006): 630.

 

Palmer, Biff F., and Robert J. Alpern. "Metabolic alkalosis." Journal of the American Society of Nephrology 8.9 (1997): 1462-1469.

 

Gennari, F. John. "Pathophysiology of metabolic alkalosis: a new classification based on the centrality of stimulated collecting duct ion transport." American Journal of Kidney Diseases 58.4 (2011): 626-636.

 

Ferrara, A., et al. "[Physiopathological and clinical data on post-hypercapnic metabolic alkalosis. A case of severe hypercapnia treated with drugs and in an" iron lung"]." Minerva medica 70.1 (1979): 67-73.

 

Banga, Amit, and G. C. Khilnani. "Post-hypercapnic alkalosis is associated with ventilator dependence and increased ICU stay." COPD: Journal of Chronic Obstructive Pulmonary Disease 6.6 (2009): 437-440.

Webster, Nigel R., and Vivek Kulkarni. "Metabolic Alkalosis in the Critically III." Critical reviews in clinical laboratory sciences 36.5 (1999): 497-510.

 

Question 9 - 2006, Paper 2

a)  Define base excess.
b)  List 2 conditions in which there is a negative base excess without any changes in the anion gap.
c)  List 1 condition in which there is an increase in the anion gap without a negative base excess.

College Answer

a) Base excess is defined as the amount of strong acid or base required to titrate pH of an in vitro sample of blood back to 7.40 at 37C at a PCO2 of 40 mm Hg.

b) Negative base excess without anion gap elevation

1)  Dilutional acidosis from saline resuscitation
2)  Renal tubular acidosis
3)  Ureterosigmoidostomy
4)  Acetazolamide therapy

c)  Lactic acidosis in a patient with pre-existing metabolic alkalosis

Discussion

Base excess definition

  • Dose of acid or base required to return the pH of a blood sample
  • Measured at standard conditions: 37°C and 40mmHg PaCO2
  • Thus, isolates the metabolic disturbance from the respiratory

Standard base excess

  • Dose of acid or base required to return the pH of an anaemic blood sample
  • Calculated for a Hb of 50g/L
  • Haemoglobin buffers both the intravascular and the extravascular fluid
  • Thus, SBE assesses the buffering of the whole extracellular fluid, not just the haemoglobin-rich intravascular fluid

"Base Excess" is the amount of acid or base required to titrate a blood sample (of whole blood) to a pH of 7.40, at standard temperature and pressure, with a standard PaCO2 of 40mmHg.

The "Standard Base Excess" is different because it uses extracellular fluid rather than whole blood. (of course, you dont sample the extracellular fluid - the ABG machine calculates the SBE for anaemic blood, with a Hb of 50g/L). The argument for this is the buffering ability of haemoglobin. It would be inappropriate to extrapolate whole blood findings to the total extracellular fluid, because though circulating haemoglobin buffers all extracellular fluid, it does so from the intravascular compartment to which it is confined.

An example of a base deficit in the presence of a normal anion gap is essentially any cause of normal anion gap metabolic acidosis- take your pick.

Examples of a normal base excess in the presence of a raised anion gap would include any situation where the high anion gap metabolic acidosis occurs in the setting of a chronic metabolic alkalosis. A favourite example is a raised lactate in the diuretic-using CCF patient, but one could just as easily use the case of the torrentially vomiting methanol drinker. LITFL also mention salicylate toxicity and HAGMA masked by uncorrected hypoalbuminaemia.

References

SIGGAARD‐ANDERSEN, O., and N. FOGH‐ANDERSEN. "Base excess or buffer base (strong ion difference) as measure of a non‐respiratory acid‐base disturbance." Acta Anaesthesiologica Scandinavica 39.s107 (1995): 123-128.

 

Ole Siggard-Andersen has his own website, which is an excellent anthology of acid-base information. This man has pioneered the concept of base excess in 1958, two years after his graduation from University of Copenhagen as candidatus medicinae (laudabilis præ ceteris et quidem egregie).

 

Kraut, Jeffrey A., and Nicolaos E. Madias. "Serum anion gap: its uses and limitations in clinical medicine." Clinical Journal of the American Society of Nephrology 2.1 (2007): 162-174.

 

Shock, Nathan W., and A. Baird Hastings. "Studies of the acid-base balance of the blood IV. Characterization and interpretation of displacement of the acid-base balance." Journal of Biological Chemistry 112.1 (1935): 239-262.

Question 18 - 2007, Paper 1

A 33 year old female presented with high fever and abdominal pain. She 
has gram negative bacteraemia and septic shock. The following are data 
from blood gas analysis. ·

Parameter

Patient Value

Normal Range

FiO2

0.3

pH

7.43

7.35 – 7.45

PaCO2

23* mmHg (3.0 kPa)

35 – 45 (4.6 – 6.0)

PaO2

107 mmHg (14 kPa)

HCO3

15* mmHg

22 – 26

Standard base excess

-8.6* mmol/l

-2 – +2

Sodium

147* mmol/l

135 – 145

Potassium

6.7* mmol/l

3.2 – 4.5

Chloride

95* mmol/l

100 – 110

Lactate

23.0* mmol/l

< 2

a} List the acid-base abnormalities

b)  What are the causes of elevated plasma lactate in sepsis? 

c)  Name 3 drugs which result in plasma hyperlactaemia

College Answer

a} List the acid-base abnormalities

High anion gap metabolic acidosis with raised lactate Metabolic alkalosis (Delta BE <Delta AG) Respiratory alkalosis

b)  What are the causes of elevated plasma lactate in sepsis? 
1)  Circulatory failure due to hypotension and hypoxia
2)  Microvascular shunting and mitochondrial failure (cytopathic hypoxia)
3)  Use of adrenaline as an inotrope
4)  Inhibition of pyruvate dehydrogenase (PDH) by endotoxin.

c)  Name 3 drugs which result in plasma hyperlactaemia
-     Catecholamines
-    Metformin Phenformin 
-      Alcohols
-    Cyanide, nitroprusside
-     Salicylates

Discussion

This question is frequently repeated. Notable duplicates include the following:

References

Grubbs, Robert D., and Michael E. Maguire. "Magnesium as a regulatory cation: criteria and evaluation." Magnesium 6.3 (1986): 113-127.

 

Martin, Kevin J., Esther A. González, and Eduardo Slatopolsky. "Clinical consequences and management of hypomagnesemia." Journal of the American Society of Nephrology 20.11 (2009): 2291-2295.

 

Chakraborti, Sajal, et al. "Protective role of magnesium in cardiovascular diseases: a review." Molecular and cellular biochemistry 238.1-2 (2002): 163-179.

Question 23 - 2007, Paper 1

Discuss the advantages and limitations of the anion gap in the evaluation of acid-base disturbance

College Answer

Definition AG -a derived variable for the evaluation of metabolic acidosis to 
determine the presence of unmeasured anions.


AG = [(Na + K)-(Cl + HC03)], normal reference range: 8-12 meq/ L


Utility: A raised AG is seen with elevated lactate, ketoacidosis, salicylates, alcohol 
poisonings, and pyroglutamate


Advantages of the anion gap: 
a) A simple measure to quantify and evaluate acid-base disturbance 
b) Can be· easily done at the bedside


Limitations: 
1) Reduced unmeasured anions such as hypoalbuminemia (frequently seen in critical 
illness) will reduce the AG and may mask an elevated AG 
2) UnmeasUred cations such as elevated Li and hyperglobulinemia will reduce AG. 
3) Hypercalcemia and hypermagnesemia will also reduce the AG. 
4) Calculation of AG involves measurement of electrolytes and therefore depends on 
the accuracy of the measurement process.


To overcome the effects of the hypoalbuminemia on the AG, the corrected AG can be 
used which is AG + (0.25 * (40-albumin) expressed in G/L

Discussion

The article by Kraut and Nicolaos is an excellent longform answer to this question.

The question itself is not even a "critically evaluate" type of question. It asks simply for the advantages and limitations.

Thus, there they are.

Advantages of the anion gap

  • Easy to calculate: (Na+ + K+) - (Cl- + HCO3-)
  • Offers a simple stratification of acid-base disorders into HAGMA and NAGMA

Limitations of the anion gap

  • Subject to laboratory error in the measurement of any of the constituents
  • Spurious sodium results can alter the anion gap (eg. in "pseudohyponatremia")
  • Spurious chloride results can alter the anion gap (eg. bromide and iodide can be mistaken for chloride in the laboratory)
  • Unmeasured or uncounted cation excess can alter the anion gap (eg. lithium, calcium, magnesium)
  • Strongly cationic drugs can decrease the anion gap, or even make it negative (eg. polymyxin B)
  • Modified by hypoalbuminaemia, and needs to be corrected (there is a 1mmol/L decrease in the "normal" anion gap for every 4g/L of albumin deficit below 40g/L)
  • Modified by hyperprotinaemia, eg. in some sort of myeloma-like illness (an excess of charged proteins changes the anion gap; it is impossible to say in which direction, as the proteins may be anionic or cationic)

A discussion of the anion gap is available locally in two forms: as a quick revision summary and as a massive rambling digression.

References

EMMETT, MICHAEL, and ROBERT G. NARINS. "Clinical use of the anion gap."Medicine 56.1 (1977): 38-54.

 

Figge, James, et al. "Anion gap and hypoalbuminemia." Critical care medicine26.11 (1998): 1807-1810.

 

Salem, Mahmoud M., and Salim K. Mujais. "Gaps in the anion gap." Archives of internal medicine 152.8 (1992): 1625-1629.

 

Kraut, Jeffrey A., and Nicolaos E. Madias. "Serum anion gap: its uses and limitations in clinical medicine." Clinical Journal of the American Society of Nephrology 2.1 (2007): 162-174.

Question 5 - 2007, Paper 2

A normotensive 39 year old female presents with severe hypokalaemia (1.1 mmol/L) and a four day history of progressive weakness. For two months she has noticed intermittent diarrhoea. She admits to taking no medication .

After 24 hours of potassium replacement at 20 mmol/hr, her strength has improved, and her blood gas and electrolyte analyses are as follows:

pH

7.45

Normal range

PaCO2

25mm Hg

HCO3-

17mmol/L

Standard base excess

-6.0mmol/L

Sodium

144mmol/L

(135 -145)

Potassium

2.9mmol/L

(3.2 - 4.5)

Chloride

119mmol/L

(100 -110)

Urea

3.2mmol/L

(3.0 - 8.0)

Creatinine

60Dmol/L

(50 - 100)

Glucose

11.0mmol/L

(3.0 – 6.0)

Ca2+

0.9mmol/L

(1.13 – 1.30)

LDH

806U/L

(100 - 200)

AST

225U/L

(10 – 45)

ALT

55U/L

(5 – 45)

ALP

92U/L

(30 – 100)

Bilirubin total

<2mmol/L

(<20)

Urinary potassium

15mmol/L

24 hr urinary

potassium excretion

18mmol

Minimum

daily urine loss

10 – 20 mmol

1.  Describe her acid-base status.

2.  What is the likely cause of the abnormal enzymes, and how can this be verified?

3.  Provide a differential diagnosis for her hypokalaemia. Give your reasoning..

College Answer

1.  Compensated respiratory alkalosis, or else a respiratory alkalosis superimposed on

a normal anion gap metabolic acidosis.

2.  Most likely rhabdomyolysis secondary to severe hypokalaemia. We need to examine muscle compartments, and measure the plasma CK.

3.  The mild metabolic acidosis may just be compensatory for her respiratory alkalosis. However, it could be a primary process (with a separate superimposed respiratory alkalosis from anxiety for example) in which case it is more consistent with enteric potassium loss, or else a proximal (Type 2) renal tubular acidosis. However urinary potassium loss of 18 mmol / day is low, and close to the obligatory minimum. Therefore bowel loss is more likely, or else transcellular potassium shifts (periodic paralysis). The persistent hypokalaemia after 24 hours of aggressive replacement makes periodic paralysis unlikely, as is the fact that this is the first episode. Apart from that, the absence of metabolic alkalosis and urinary potassium wasting are against Cushing’s and Conn’s syndromes as well as diuretic abuse, and the absence of hypertension is also against Cushing’s and Conn’s syndrome. Therefore on balance and with the history of diarrhoea, bowel loss is the most likely.

Bowel loss (eg villous adenoma, aperient abuse)

Diuretic abuse

Conn’s syndrome

Cushing’s syndrome

Periodic paralysis.

Renal tubular acidosis

Discussion

Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated
  2. There is no acidaemia
  3. The PaCO2 suggests a compensatory respiratory alkalosis
  4. The SBE is -6, suggesting a metabolic acidosis
  5. The respiratory compensation is excessive; the expected PaCO2(17 × 1.5) + 8 = 33.5mmHg, and thus there is definitely also a respiratory alkalosis
  6. The anion gap is normal:
    (144) - (119 + 17) = 8, or 10.9 when calculated with potassium

The urinary potassium loss is also normal, suggesting that gastrointestinal potassium losses must account for this hypokalemia.

Thus: this is a normal anion gap metabolic acidosis with respiratory alkalosis.

Let us leave the respiratory alkalosis well alone for the moment.

There are several differentials  for NAGMA.

The college asks for an explanation of the raised enzyme levels. The LDH and AST are not exclusively hepatic enzymes; they can also leak from damaged muscle, and the lady has presented with weakness, which might suggest that she is suffering from hypokalemia-associated rhabdomyolysis (though unless I am grossly mistaken, damaged muscle should also leak potassium, resulting in hyperkalemia). Certainly a CK an urinary/serum myoglobin levels will set this matter straight.

Differential diagnosis of hypokalemia is discussed at lengths elsewhere.

Below is a table of differentials which is organised according to the findings of investigations.

Causes of Hypokalemia

Low urinary potassium

High urinary potassium with acidosis

  • Distal tubular acidosis (Type 1)
  • Proximal tubular acidosis (Type 2)
  • Diabetic ketoacidosis

High urinary potassium with alkalosis

  • Diuretics
  • Gastrointestinal secretion losses (eg. vomiting, excessive NG suction, etc)
  • Bartter syndrome
  • Gitelman syndrome
  • Derangement of renin-aldosterone axis
    • Low renin, high aldosterone
      • Primary hyperaldosteronism
    • High renin, high aldosterone
      • Cardiac failure
      • Renal artery stenosis
      • Renin-secreting tumours
    • Low renin, low aldosterone
      • Adrenal hyperplasia
      • Cushing syndrome
      • Exogenous corticosteroid excess
      • Liddle syndrome
    • Cushings disease
    • Exogenous corticosteroid excess
    • Adrenal hyperplasia

This lady falls into the "low urinary potassium" category, which suggests that the potassium losses are occurring though the gut. Familial hypokalemic periodic paralysis is not out of the question, but this tends to start in adolescence so its unlikely.

The absence of alkalosis and hypertension steers the candidate away from thinking about the derangements of the renin-angiotensin-aldosterone axis. There is a normal anion gap metabolic acidosis present, which could be contributing to the picture. Of the possibilities, one may focus most on Type 1 and Type 2  renal tubular acidosis, seeing as Type 4 renal tubular acidosis tends to cause hyperkalemia instead. Of course, in all forms of hypokalemic RTA, the renal potassium losses are significant, and one would not have such a tiny 24-hour urinary K+ level. And on top of that the hypokalemic forms of RTA tend to present with profound acidosis - the pH would be very abnormal and the HCO3- would be very low.

References

Singhal, P. C., et al. "Hypokalemia and rhabdomyolysis." Mineral and electrolyte metabolism 17.5 (1990): 335-339.

 

Assadi, Farahnak. "Diagnosis of hypokalemia: a problem-solving approach to clinical cases." Iranian journal of kidney diseases 2.3 (2008): 115-122.

 

Weiner, I. David, and Charles S. Wingo. "Hypokalemia--consequences, causes, and correction." Journal of the American Society of Nephrology 8.7 (1997): 1179-1188.

 

Links, Thera P., et al. "Familial hypokalemic periodic paralysis: clinical, diagnostic and therapeutic aspects." Journal of the neurological sciences 122.1 (1994): 33-43.

 

Gennari, F. John. "Hypokalemia." New England Journal of Medicine 339.7 (1998): 451-458.

 

Huang, Chou-Long, and Elizabeth Kuo. "Mechanism of hypokalemia in magnesium deficiency." Journal of the American Society of Nephrology 18.10 (2007): 2649-2652.

 

Question 6.1 - 2008, Paper 1

16 year old male has been treated all night for diabetic ketoacidosis. In the morning the blood gas printout is as follows:

Barometric pressure

760mm Hg

FiO2

0.21

pH

7.32

pO2

100mm Hg (13.2 kPa)

pCO2

30mm Hg    (4kPa)

HCO3-

15.2mmol/L

Standard base excess

-11.4mmol/L

Sodium

136mmol/L

(135 – 145)

Chloride

105mmol/L

(100 -110)

Potassium

3.5mmol/L

(3.2 - 4.5)

Lactate

1.3mmol/L

(0.2 - 2.5)

Glucose

5.3mmol/L

(3.6 – 7.7)

a) Describe the acid-base status.

b) Does he need continuation of insulin therapy over the next 6 hours? Give your reasoning.

College Answer

a) Describe the acid-base status.
Raised anion gap metabolic acidosis with appropriate respiratory compensation

b) Does he need continuation of insulin therapy over the next 6 hours? Give your reasoning.

The patient will require insulin therapy for the next few hours as the anion gap is raised, indicating ongoing ketoacidosis.

Discussion

Let us dissect these results systematically.
 

  1. The A-a gradient is normal.
    PAO2 = (0.21 × 713) - (30 × 1.25) = 112.2
    Thus, A-a = ( 112.2 - 100) = 12.2mmHg.
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is -9.9, suggesting a metabolic acidosis
  5. The respiratory compensation is adequate - the expected PaCO2(15.2 × 1.5) + 8 = 30.8mmHg
  6. The anion gap is (136) - (105 + 15) = 16, or 19.5 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (16 - 12) / (24 - 15) = 0.44. This delta ratio suggests that there is a mixed high anion gap and normal anion gap metabolic acidosis

This questions would seem identical to Question 7.1 from the first paper of 2009, but the examiners have changed the chloride and glucose. In 2009, this 16 year old patient has a normal anion gap and slightly raised glucose, forcing us to conclude that the ketoacidosis has resolved. No mention is made of insulin.

This time, the ketoacidosis persists. One would be tempted to continue the insulin/dextrose infusion until the anion gap is normal, and only the NAGMA remains.

References

UpToDate has a nice summary of this topic for the paying customer.

Oh's Intensive Care manual: Chapter 58  (pp. 629) Diabetic  emergencies  by Richard  Keays

Umpierrez, Guillermo E., Mary Beth Murphy, and Abbas E. Kitabchi. "Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome." Diabetes Spectrum15.1 (2002): 28-36.

Question 6.3 - 2008, Paper 1

Sodium 143  mmol/L (137-145)
Potassium 2.6   mmol/L (3.1-4.2)
Chloride 117  mmol/L (101-109)
Bicarbonate   18 mmol/L (22-32)
Urea       7.0  mmol/L   (3.0-8.0)
Creatinine  0.08 mmol/L (0.05-0.12)

List 3 likely causes for the above plasma biochemistry

College Answer

Drugs:

1) RTA 1 or 2
2) Ampho B,
3) Acetazolamide
4) GI losses

Discussion

Let us dissect this set of results.

There is some sort of acidosis. There is no SBE, but the bicarbonate is 18. The anion gap is (143) - (117 + 18) = 8, or 10.6 when calculated with potassium

Thus, it is a normal anion gap metabolic acidosis.

What could possibly cause a normal anion gap metabolic acidosis?

In the absence of history, one falls back on broad differentials:

  • Pancreatic secretion loss
  • Acetazolamide, or renal tubular acidosis Type 2
  • Normal saline intoxication
  • Diarrhoea
  • Aldosterone antagonists
  • Renal tubular acidosis Type 1 (distal)
  • Ureteric diversion
  • Small bowel fistula
  • Hyperalimentation (TPN)

Those offered by the college are frankly bizarre. I cannot imagine how a candidate could have scored full marks with that. Acetazolamide use is a pharmacological form of Type 2 RTA, and "Ampho B" probably refers to amphotericin-induced distal (Type 2) renal tubular acidosis (and I cannot imagine how even the most time-constrained examiner might have been so rushed that they actually failed to finish the word "amphotericin" in their model answer).

Thus, the three non-overlapping causes I would have given would be the following:

  • Normal saline intoxication
  • Renal tubular acidosis (Type 1 or 2) - not 4, as the K+ is low
  • Diarrhoea or other gastrointestinal losses

References

Story DA. Hyperchloraemic acidosis: another misnomer? Crit Care Resusc. 2004 Sep;6(3):188-92.

Question 7 - 2008, Paper 1

List the causes of metabolic alkalosis and explain how you will evaluate a patient with metabolic alkalosis.

College Answer

Evaluation of causes of metabolic alkalosis requires a systematic approach involving history, examination and some specific investigations. Categories of aetiology include
• loss of hydrogen ions (gastrointestinal, renal)

• intracellular shift of hydrogen ions

• administration of alkali

• contraction alkalosis

•    History and examination will reveal, documented fluid losses

-(vomiting & gastric losses, laxative induced diarrhoea),

-signs of volume depletion (loss of bicarbonate free fluids),

- administered drugs (mineralocorticoids, diuretics , and antacids in renal failure) , alkali (bicarbonate, lactate, citrate etc)

• and recent hypercapnia.

• Blood investigations may reveal hypokalemia (with hydrogen shifting into cells), hypochloremia

•    Urinary findings may include excessive potassium excretion (reabsorbing hydrogen), alkaline pH (increased bicarbonate) and inappropriately elevated chloride excretion (diuretic therapy, hypokalaemia).

•          Using Stewart’s physicochemical approach, an isolated increase in Strong ion difference (SID) seen with the use of solutions such as plasmalyte or NaHCO3 or a reduction in ATOT seen with hypoalbuminemia can lead to metabolic alkalosis

Discussion

The diagnostic approach to metabolic alkalosis is discussed in more detail elsewhere.

Instead of a text excess, I will reproduce the diagnostic flowchart which was suggested by a Medscape article, and which seemed like a nice way of remembering this process.

diagnostic algorithm for metabolic alkalosis

This flowchart can be converted into the form of a point-form answer:

  • History and examination
    • Recent exogenous bicarbonate administration
    • Milk-alkali syndrome
    • Hypercalcemia
    • β-lactam use
    • Cystic fibrosis
  • Low urinary chloride
    • Recent diuretic therapy
    • Gastric losses via NG suction or vomiting,
    • Villous adenoma of colon
    • Post-hypercapneic (compensatory) alkalosis
  • High urinary chloride and normal blood pressure
    • Ongoing diuretic therapy (must be effective, the blood pressure is normal...)
    • Bartter syndrome
    • Gitelman’s syndrome
    • Hypokalemia
    • Hypomagnesaemia
  • High urinary chloride, hypertension and high renin activity
    • Ongoing diuretic therapy
    • Renal artery stenosis
    • Renin-secreting tumour
    • Malignant hypertension
  • High urinary chloride, hypertension and normal renin-aldosterone axis
    • Cushing syndrome
    • Corticosteroid use
    • 17-hydroxylase deficiency
    • Liddle’s syndrome
    • Licorice overindulgeance
  • High urinary chloride, hypertension and hyperaldosteronism without high renin levels
    • Adrenal adenoma
    • Adrenal hyperplasia
    • Aldosterone synthase hyperactivity

Thus, the following is a list of the necessary details one will need to determine from the patients history, physical examination, and biochemistry values:

Background history

  • History of congential adrenal hypoplasia
  • History of cystic fibrosis
  • History of CCF (suggesting chronic exposure to diuretics)
  • History of uncontrolled hypertension (malignant hypertension or renal artery stenosis)

Recent history

  • Recent antacic consumption
  • Recent use of calcium supplements
  • β-lactam antibiotic use
  • Massive abuse of licorice
  • History of diarrhoea (villous adenoma) or vomiting (chloride loss)
  • History of recent hypercapneic respiratory failure

Examination

  • Clinically, findings consistent with severe hypertension (eg. retinal changes)
  • Renal artery stenosis bruit
  • Peripheral oedema (suggesting chronic exposure to diuretics)

Biochemistry

  • Serum potassium
  • Serum magnesium
  • Urinary chloride
  • Serum renin levels
  • Serum aldosterone levels

References

Gennari, F. John. "Pathophysiology of metabolic alkalosis: a new classification based on the centrality of stimulated collecting duct ion transport." American Journal of Kidney Diseases 58.4 (2011): 626-636.

Tripathy, Swagata. "Extreme metabolic alkalosis in intensive care." Indian journal of critical care medicine: peer-reviewed, official publication of Indian Society of Critical Care Medicine 13.4 (2009): 217.

Galla, John H. "Metabolic alkalosis." Journal of the American Society of Nephrology 11.2 (2000): 369-375.

Pahari, D. K., et al. "Diagnosis and management of metabolic alkalosis."JOURNAL-INDIAN MEDICAL ASSOCIATION 104.11 (2006): 630.

Palmer, Biff F., and Robert J. Alpern. "Metabolic alkalosis." Journal of the American Society of Nephrology 8.9 (1997): 1462-1469.

Gennari, F. John. "Pathophysiology of metabolic alkalosis: a new classification based on the centrality of stimulated collecting duct ion transport." American Journal of Kidney Diseases 58.4 (2011): 626-636.

Question 3.1 - 2008, Paper 2

A 43 year old man, with no history of previous illnesses is admitted with septic shock requiring administration of high dose vasopressor. His blood results on 40% oxygen, pressure support ventilation are as follows:

Parameter

Value

Normal range

pH

7.64

7.35-7.45

PaCO2

28 mmHg (3.7 kPa)

35-45 mmHg (4.7-6.0 kPa)

PaO2

189 mmHg (25.2 kPa)

75-98 mmHg (10.0-13.0 kPa)

Actual
bicarbonate

29 mmol/l

22-26 mmol/l

Sodium

147 mmol/l

134-145 mmol/l

Potassium

3.5 mmol/l

3.5-5.1 mmol/l

a. Describe the acid-base  abnormality
b. List 3 likely causes of each acid-base  abnormality in this patient.

College Answer

a. Describe the acid-base abnormality

Respiratory and metabolic alkalosis

b. List 3 likely causes of each acid-base abnormality in this patient. Respiratory alkalosis: Hyperventilation – spontaneous or IPPV induced, septic
encephalopathy, pneumonia
Metabolic alkalosis: Diuretics, volume contraction, upper GI losses, steroids.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is normal.
    PAO2 = (0.4 × 713) - (28 × 1.25) = 250.2
    Thus, A-a = ( 250.2 - 189) = 61.2mmHg.
  2. There is alkalaemia
  3. The PaCO2 is contributing to the alkalaemia
  4. The SBE is not supplied, but the bicarbonate is 29, suggesting that there is a metabolic alkalosis.
  5. If the metabolic alkalosis is the primary disorder, then there is no respiratory compensation- the expected PaCO2(29 × 0.7) + 20 = 40.3mmHg. Alternatively, if we assume that acute respiratory alkalosis is the primary disorder, then the expected bicarbonate is 26.4mmol/L: 
    (measured bicarbonate + 2mmol/L per every 10mmHg decrease in PaCO2). Thus, there are two coexisting disorders - a metabolic alkalosis and a respiratory alkalosis - irrespective of how you look at it.

What the hell is driving this derangement in this septic patient?

The disturbances are not connected. Each likely has a separate cause.

The respiratory alkalosis can be driven by spontaneous hyperventilation, or by excessive mechanical ventilation (i.e. somebody has increased the pressure support level to a point where the patient is generating unnecessarily massive tidal volumes). Alternative explanations include pain, encephalopathy (of whatever cause) and pneumonia.

The  causes of metabolic alkalosis are numerous; those relevant to this question can include the following:

  • Gastric losses by vomiting or drainage
  • Diuretics: loop diuretics or thiazides
  • Diarrhoea 
  • Posthypercapneic state (hypercapnea recently reversed by mechanical ventilation)
  • Recent use of corticosteroids
  • Hypoalbuminaemia

References

Sankaran, Ramkumar T., et al. "Laboratory abnormalities in patients with bacterial pneumonia."CHEST Journal 111.3 (1997): 595-600.

Question 3.2 - 2008, Paper 2

A 41 year old man is admitted to your Emergency Department, unconscious, with the first set of blood results. The second set of blood gases are taken  1 hour later.

Parameter

Initial values

1 hour later

Normal range

pH

7.05

7.35

7.35-7.45

PaCO2

34 mmHg (4.6
kPa)

39 mmHg (5.2 kPa)

35-45 mmHg (4.7-6.0
kPa)

PaO2

203 mmHg (33.6 kPa)

94 mmHg (12.5 kPa)

75-98 mmHg (10.0-
13.0 kPa)

Actual bicarbonate

9 mmol/l

21

22-26 mmol/l

Sodium

137 mmol/l

134-145 mmol/l

Potassium

4.2 mmol/l

3.5-5.1 mmol/l

Glucose

11.2 mmol/l

Ionised
Calcium

1.21 mmol/l

2.15-2.55 mmol/l

Chloride

105 mmol/L

95-105 mmol/L

a. Describe the initial acid-base  disturbance
b. List 3 clinical scenarios which may produce such a pattern of arterial blood gas derangement?

College Answer

3.2a. The initial acid-base disturbance is a mixed metabolic and respiratory acidosis with a raised anion gap.

3.2b. Seizures
Resuscitated cardiac arrest
Near drowning
Near hanging

Discussion

This question is identical to Question 15.2 from the second paper of 2009.

References

Question 3.3 - 2008, Paper 2

A 48 year old diabetic  with a history of alcohol abuse is admitted with abdominal pain and the following results:

Parameter

Value

Normal range

pH

6.87

7.35-7.45

PaCO2

8 mmHg (1.1 kPa)

35-45 mmHg (4.7-6.0 kPa)

PaO2

149 mmHg (20 kPa)

75-98 mmHg (10.0-13.0 kPa)

Actual bicarbonate

1.4 mmol/l

22-26 mmol/l

Lactate

16 mmol/l

<2 mmol/l

Sodium

142 mmol/l

134-145 mmol/l

Potassium

4.7 mmol/l

3.5-5.1 mmol/l

Urea

14 mmol/l

3.4-8.9 mmol/l

Creatinine

170 micromol/L

(60-110 micromol/L)

AST

60

(<40 U/L)

ALT

70

(<40U/L)

LDH

1400

50-150 U/L

Total bilirubin

20

4-25 micromol/L)

Glucose

6.5 mmol/l

Serum osmolality

314

275-295 mOsm/kg

a. Give the three most likely diagnoses
b. List two additional investigations that you would perform based on the above information

College Answer

3.3
a) Diagnoses: 3 ischaemic bowel, 2 metformin induced lactic acidosis, thiamine deficiency, pancreatitis.

b) Two of the following investigations: Diagnostic laparoscopy or laparotomy, CT abdomen, red cell transketolase, lipase

Discussion

This question is identical to Question 15.3 from the second paper of 2009.

References

Question 9.1 - 2008, Paper 2

Outline  how pH, PCO2 and PO2  are measured in a blood gas analyser and briefly state the underlying principle behind  each of those measurements.

College Answer

pH  –                glass electrode,   The specimen is put in a capillary tube surrounded by buffer solution. The tube is made of pH sensitive glass across which a potential difference is generated,           Measures potential difference across the electrodes


PCO2                    modified glass electrode , comprises a glass pH electrode which is in contact with a thin film of NaHCO3 solution. This is separated from the specimen by a membrane that is permeable to CO2 – CO2 diffuses from specimen into the HCO3 solution where it dissociates with a change in pH which is measured by the electrode. Measures potential difference across the electrodes


PO2 –               Clark electrode or polarographic electrode,   polarographic or measures current generated (an amperometric system) or the current flow across the Clark electrode is determined by the PO2 of the solution

Discussion

The scientific principles behind the measurements which magically occur behind the shiny glass of the ABG machine are discussed in greater detail elsewhere

In brief:

  • pH is measured by a glass electrode
    • The potential difference across the electrode is proportional to the pH difference, and this can be measured.
  • PaCO2 is measured by a modified glass electrode
    • The electrode contains some sodium bicarbonate, which reacts with the CO2; the reaction changes the pH in the electrode, which corresponds to a change in potential difference, and this is measured. The CO2 is then inferred from the change in pH.
  • PO2 is measured by a Clark electrode or polarographic electrode
    • O2 in an aqueous buffer is reduced to OH- ions with the application of current (600-800mV); this causes a current to flow between two submerged electrodes. Increasing the voltage across this system also increases the current - up to a plateau. The plateau level depends upon, and is proportional to, the concentration of oxygen.

References

 

LITFL give a good overview, in sufficient detail for the time-poor exam candidate:

The best resource for this sort of stuff is the handbook and user guide for the blood gas machine. The brief brochure for our hometown machine can be found here, at the Radiometer website.

There is also a comprehensive operations manual.

The Radiometer Blood Gas Handbook is also a valuable resource. However, it tries to explain what the parameters mean for clinical decisionmaking, rather than how they are measured.

An excellent professional resource on this topic can be found at The Deep Picture.

And if one wants to go to town on this topic, Severinghaus (yes, THE Severinghaus) has published a series of articles on this theme:

Severinghaus, John W., and Paul B. Astrup. "History of blood gas analysis. I. The development of electrochemistry." Journal of clinical monitoring 1.3 (1985): 180-192.

Severinghaus, John W., and Poul B. Astrup. "History of blood gas analysis. II. pH and acid-base balance measurements." Journal of clinical monitoring 1.4 (1985): 259-277.

Severinghaus, John W., and Poul B. Astrup. "History of blood gas analysis. III. Carbon dioxide tension." Journal of clinical monitoring 2.1 (1986): 60-73.

Severinghaus, John W., and Poul B. Astrup. "History of blood gas analysis. IV. Leland Clark's oxygen electrode." Journal of clinical monitoring 2.2 (1986): 125-139.

Severinghaus, John W., and Poul B. Astrup. "History of blood gas analysis. V. Oxygen measurement." Journal of clinical monitoring 2.3 (1986): 174-189.

Severinghaus, John W., and Poul B. Astrup. "History of blood gas analysis. VI. Oximetry." Journal of clinical monitoring 2.4 (1986): 270-288.

Severinghaus, John W., and Yoshiyuki Honda. "History of blood gas analysis. VII. Pulse oximetry." Journal of clinical monitoring 3.2 (1987): 135-138.

Question 18.2 - 2008, Paper 2

A 63 year old patient with a background of type II diabetes  had vascular surgery 24 hours previously. His post operative course has been uncomplicated except for consistently  elevated serum potassium measurements. He is not receiving supplemental potassium and vital recordings have been stable. His most recent arterial blood gases and plasma  biochemistry are presented below:

Arterial blood

Value

Reference range

pH

7.24

7.36-7.44

PCO2

24 mmHg  (3.2 kPa)

40 mmHg       (5.3-5.7 kPa)

PO2

90 mmHg (12.0 kPa)

80-100 mmHg (10.5-13.0 kPa)

HCO3 -

10

22-33 mmol/L

Na+

135

135 -145 mmol/L

K+

5.7

3.2-4.5 mmol/L

Urea

15

3.0-8.0 mmol/L

Creatinine

180

50-100 umol/L

Cl -

120

100-110 mmol/L

Albumin

35

35-50 G/L

a) Describe the acid base abnormality

b) List three causes of the acid-base  abnormality.

c)  What is the most likely cause of the abnormality in this patient?

College Answer

a) Describe the acid base abnormality

This is a normal anion gap metabolic acidosis.

b) List three causes of the acid-base  abnormality.

The major causes are:
o   Loss of bicarbonate (eg diarrhoea, pancreatic biliary drainage and urinary diversions (ureterosigmoidostomy)
o   Renal tubular acidosis (RTA).
o   Other: saline loading, TPN and cholestyramine use. 

c)  What is the most likely cause of the abnormality in this patient?

Type 4 RTA.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated, as no FiO2 is supplied to us
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is not supplied, but the bicarbonate is 10, suggesting a severe metabolic acidosis
  5. The respiratory compensation is adequate and lurks around the natural limits of human respiratory compensation for metabolic acidosis- the expected PaCO2(10 × 1.5) + 8 = 23mmHg
  6. The anion gap is (135) - (120 + 10) = 5, or 10.7 when calculated with potassium.
  7. Urinary pH and electrolytes are not supplied, but they would be interesting.

Three causes of normal anion gap metabolic acidosis?

The mnemonic PANDA RUSH comes to mind, even though it is not very good.

  • Pancreatico-duodenal fistula
  • Acetazolamide
  • Normal saline intoxication (or any other sort of exogenous chloride excess)
  • Diarrhoea
  • Aldosterone antagonists
  • Renal tubular acidosis Type 1 (distal)
  • Ureteric diversion
  • Small bowel fistula
  • Hyperalimentation (TPN)

In the question text, the college harps on about the raised potassium. Truly, there is only one sort of normal anion gap acidosis which is stereotypically associated with hyperkalemia:  Type 4  renal tubular acidosis, or the use of spironolactone. Of all the other causes, none have any firm commitment to hyperkalemia.

References

Laing, Christopher M., et al. "Renal tubular acidosis: developments in our understanding of the molecular basis." The international journal of biochemistry & cell biology 37.6 (2005): 1151-1161.

An excellent overview of the physicochemical approach to RTA can be found in this article from Critical Care.

Ring, Troels, Sebastian Frische, and Søren Nielsen. "Clinical review: Renal tubular acidosis–a physicochemical approach." Critical Care 9.6 (2005): 573.

Question 7.1 - 2009, paper 1

A 16 year old male has been treated all night for diabetic ketoacidosis. In the morning the blood gas printout is as follows:

Barometric pressure

760mm Hg

FiO2

0.21

pH

7.32

pO2

100 mm Hg(13.3 kPa)

pCO2

30 mm Hg (4 kPa)

HCO3-

15.0mmol/L

Standard base excess

-9.9mmol/L

Sodium

135mmol/L

(135 – 145)

Chloride

114mmol/L

(100 -110)

Potassium

3.5mmol/L

(3.2 - 4.5)

Lactate

1.3mmol/L

(0.2 - 2.5)

Glucose

14.3mmol/L

(3.6 – 7.7)

a) Describe the acid-base status.
b) Has the keto-acidosis resolved? Give your reasoning.

College Answer

Q7.1a) Normal anion gap metabolic acidosis with appropriate respiratory compensation.

Q7.1b) Yes The anion gap is normal, indicating resolution of ketoacidosis. The persistent acidosis reflects saline fluid replacement coupled with the chloride retention during the period of ketonuria.

Discussion

Let us dissect these results systematically.
 

  1. The A-a gradient is normal.
    PAO2 = (0.21 × 713) - (30 × 1.25) = 112.2
    Thus, A-a = ( 112.2 - 100) = 12.2mmHg.
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is -9.9, suggesting a metabolic acidosis
  5. The respiratory compensation is adequate - the expected PaCO2(15 × 1.5) + 8 = 30.5mmHg
  6. The anion gap is (135) - (114 + 15) = 6, or 9.5 when calculated with potassium. 

Has the ketoacidosis resolved? Well, there is no more anion gap, so yes- one would be forced to conclude that it has. A normal anion gap acidosis now prevails, likely due to either vigorous resuscitation with normal saline, or to the normal hyperchloraemia in the recovery phase of ketoacidosis.

References

Oh, M. S., H. J. Carroll, and J. Uribarri. "Mechanism of normochloremic and hyperchloremic acidosis in diabetic ketoacidosis." Nephron 54.1 (1990): 1-6.

Question 7.2 - 2009, paper 1

You are asked to review a drowsy 80-year-old male with chronic obstructive pulmonary disease, 6 hours after internal fixation of a fractured hip. He is normotensive, and rousable with stimulation. The following are data from arterial blood.

Barometric pressure

760mm Hg

FiO2

0.4

pH

7.47

pO2

170mm Hg 22.6 (kPa)

pCO2

65mm Hg 8.6 (kPa)

HCO3-

46.6mmol/L

Standard base excess

20.9mmol/L

a) Describe the acid- base status.
b) List four measures which might improve his acid-base status (apart from mechanical ventilation).

College Answer

Q7.2a) Metabolic alkalosis and respiratory acidosis.
Q7.2b) Cease narcotics; Naloxone (cautious); Reduce FiO2 and titrate to SpO2 90-95%; Reverse metabolic alkalosis (acetazolamide, KCl if hypokalaemia).

Discussion

Let us dissect these results systematically.
 

  1. The A-a gradient is almost normal.
    PAO2 = (0.4 × 713) - (65 × 1.25) = 203.95
    Thus, A-a = ( 203.95 - 170) = 33.95mmHg.
  2. There is no acidaemia
  3. The PaCO2 is raised, suggesting a respiratory acidosis. The history suggests that this is probably the primary disorder.
  4. The SBE is 20.9, suggesting a metabolic alkalosis
  5. The metabolic compensation is excessive. The PaCO2 increase is (65 - 40)/10 = 2.5; if this were an acute respiratory acidosis we would expect a HCO3around 26.5 mmol/L (bicarbonate + 2.5 × 1), and if it were chronic we would expect 34 mmol/L (bicarbonate + 2.5 × 4). There must also be a metabolic alkalosis. 
    If the metabolic alkalosis were thought to be the primary disorder, the respiratory compensation would appear to be excessive: the expected PaCO(0.7 × 46.6) + 20 = 52.6mmHg. Thus, any way you look at it, there is both a metabolic alkalosis and a respiratory acidosis.

So. This 80-year-old has enjoyed a nice dose of perioperative opiates, and is now drowsy. The metabolic alkalosis is preventing acidaemia from developing, and the CO2 climbs ever higher, fogging up the level of consciousness. This is not helped by the generous oxygenation, which has abolished the normal contribution of hypoxic respiratory drive. Imagine: if this patient was on room air, the alveolar gas equation yields a PAOof only 68mmHg; and with his elderly lungs in charge of gas exchange the PaO2 would be in the 50s, driving the respiratory effort.

Thus, there are various ways of dealing with this acid-base disturbance.

  • Stop the opiates.
  • Stop the oxygen. Go with room air, or whatever is required to maintain an SpO2 of 88-90% (the college generously recommends 90-95%)
  • Reverse the opiates with naloxone
  • Stop the diuretics
  • Administer sodium chloride, potassium chloride or ammonium chloride.
  • Administer acetazolamide

References

Question 7.3 - 2009, paper 1

A 21 year old female is brought to ICU extubated post Caesarian section for pre- eclampsia and foetal distress. The following are data from blood gas analysis.

Barometric pressure 760 mm Hg


FiO2


0.5

pH

7.31

pO2

150 mm Hg

20 kPa

pCO2

42  mm Hg

5.6 kPa

HCO3-

20.5

mmol/L

Standard base excess

-4.9

mmol/L

a) Describe and explain the acid-base status.
b) If she had normal lung function, what should her PaO2  be?
c) Name three possible causes of her reduced oxygen transfer?

College Answer

Q7.3a) Acute respiratory acidosis following previous compensated respiratory alkalosis of pregnancy. At 38 weeks pregnancy the normal PaCO2 is <30 mm Hg with compensatory HCO3- reduction. The blood gases therefore indicate acute CO2 retention, probably due to pain and narcotics.

Q7.3b) > 250 mm Hg.

Q7.3c) Potential explanations include loss of FRC post abdominal surgery, segmental collapse or consolidation, aspiration, pulmonary oedema.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high:
    PAO2 = (0.5 × 713) - (42 × 1.25) = 304
    Thus, A-a = ( 304-150) = 104mmHg.
  2. There is acidaemia
  3. The PaCO2 is contributing to the acidosis
  4. The SBE is -4.9, suggesting a metabolic acidosis
  5. The respiratory compensation would seem inadequate - the expected PaCO2(20.5 × 1.5) + 8 = 38.75mmHg; given that at the end of pregnancy the normal CO2 is around 30mHg, this would represent a respiratory acidosis.

However, one should point out that the empirical rules for blood gas interpretation were developed from data collected in non-pregnant individuals, and do not account for the changes in homeostatic setpoints of pregnancy. Indeed, if we were to consider that the pregnant woman has well-compensated respiratory alkalosis at term (with a chronically decreased PaCO2, down to 30mmHg) we would expect the HCO3- to decrease by 5mmol/L, which would give us an expected HCO3- of 19mmol/L.

If this pregnant woman with a HCO3- of 19mmol/L were to suddenly develop a respiratory acidosis, the HCO3- would increase by 1mol/L for every 10mmHg of PaCO2 elevation. The expected HCO3- in this woman would therefore be slightly over 20mmol/L; ... which it is. Thus, there is probably no metabolic acid-base disturbance here.

The normal arterial oxygen for this woman should be well over 270, especilly if she had a normal PaCO2.

Why is the A-a gradient so great?

Apart from the guesses offered by the college ("loss of FRC post abdominal surgery, segmental collapse or consolidation, aspiration, pulmonary oedema") one can also suggest PE, amniotic fluid embolism and cardiomyopathy of pregnancy. In addition, merely being supine can cause modest hypoxia in pregnant women at term, though this is a pre-partum phenomenon.

References

AWE, ROBERT J., et al. "Arterial oxygenation and alveolar-arterial gradients in term pregnancy." Obstetrics & Gynecology 53.2 (1979): 182-186.

Milne, J. A. "The respiratory response to pregnancy." Postgraduate medical journal 55.643 (1979): 318-324.

Yeomans, Edward R., and Larry C. Gilstrap III. "Physiologic changes in pregnancy and their impact on critical care." Critical care medicine 33.10 (2005): S256-S258.

Fadel, Hossam E., et al. "Normal pregnancy: a model of sustained respiratory alkalosis." Journal of Perinatal Medicine-Official Journal of the WAPM 7.4 (1979): 195-201.

Question 19.2 - 2009, paper 1

List 3 drugs or poisons that, when taken as an overdose, result in both a raised osmolar gap and anion gap. List the major anion associated with each drug responsible for the rise in anion gap.

College Answer

Drug                                            Anion
Ethanol                                   - Lactate
Methanol                                 - Formate or formic acid
Ethylene glycol                       - Glycolate / oxalate

Discussion

Ethanol overindulgeance can indeed cause a lactic acidosis, but I would have chosen a different drug:

  • Toxicological causes of high anion and high osmolar gap
    • Methanol intoxication (the anion is formic acid)
    • Ethylene glycol intoxication (the anions are glycolic acid and oxalic acid)
    • Diethylene glycol intoxication (the anion is 2-hydroxyethoxyacetic acid, HEAA)
    • Propylene glycol intoxication (the anions are pyruvate, lactate and acetate)
    • Salicylate intoxication (the anions are salicylate and lactate)
    • Any toxin causing massive lactic acidosis, eg. isoniazid
  • Endocrine and metabolic causes of high anion and high osmolar gap
    • Lactic acidosis
    • Alcoholic or diabetic ketoacidosis
    • Acute kidney injury

References

Erstad, Brian L. "Osmolality and osmolarity: narrowing the terminology gap."Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy23.9 (2003): 1085-1086.

Gennari, F. John. "Current concepts. Serum osmolality. Uses and limitations."The New England journal of medicine 310.2 (1984): 102-105.

Hoffman, Robert S., et al. "Osmol gaps revisited: normal values and limitations."Clinical Toxicology 31.1 (1993): 81-93.

Dorwart, William V., and Leslie Chalmers. "Comparison of methods for calculating serum osmolality from chemical concentrations, and the prognostic value of such calculations." Clinical chemistry 21.2 (1975): 190-194.

Kraut, Jeffrey A., and Shelly Xiaolei Xing. "Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis." American Journal of Kidney Diseases 58.3 (2011): 480-484.

Question 13 - 2009, Paper 2

A 45 year old previously healthy man was admitted to your ICU five (5) days ago after a motor vehicle accident with chest and abdominal injuries. He is currently intubated and ventilated, is on 100% oxygen and PEEP of 10cm water. He is deeply sedated and on noradrenaline and adrenaline infusions at 10mcg/min each. He has become oliguric.

His blood biochemistry, haematology and arterial blood gases are as follows:

Venous biochemistry

Test

Value

Normal Range

Sodium

138 mmol/L

135 -145

Potassium*

7.1 mmol/L

3.5 - 4.5

Chloride

104 mmol/L

95 -105

Urea*

27 mmol/L

2.9 - 8.2

Creatinine*

260   mol/L

70 -120

Haematology

Test

Value

Normal Range

Hb*

120 G/L

135 -180

WBC*

12.8 x 109/L

4.0 -11.0

Platelets*

42 x 109/L

140 - 400

Arterial blood gases

Test

Value

Normal Range

pH*

7.01

7.35 – 7.45

PCO2*

45 mm Hg (6 kPa)

40 - 44

PO2*

70 mm Hg (9.3 kPa)

80 - 100

Bicarbonate*

11 mmol/L

22 - 26

Base Excess*

-19 mmol/L

-2.0 to +2.0

Glucose*

7.5 mmol/L

4 - 6

Lactate*

13 mmol/L

<2.0

13.1     Summarise the findings of the blood tests.

13.2     What are the likely underlying causes of the lactic acidosis?

13.3     What are your management priorities at this point?

College Answer

13.1     Summarise the findings of the blood tests.

•    High anion gap metabolic acidosis (with apparent normal SID). Note AG 33 which is NOT adequately explained just by a lactate of 13 mmol
•    Inadequate or inappropriate respiratory compensation
•    Hypoxaemia (P/F ratio 70)
•    Acute renal failure (note urea:creatinine ratio).
•    Hyperkalaemia

13.2     What are the likely underlying causes of the lactic acidosis?

•    Sepsis with shock
•    Ongoing hypovolaemia
•    Hypoperfusion eg septic cardiomyopathy; abdominal compartment syndrome
•    Possible gut ischemia
•    Perhaps adrenaline (also seen with other catecholamines – unpredictable

13.3     What are your management priorities at this point?

•    Optimise cardiovascular function. Urgent echocardiogram. Volume replacement if possible. Measure continuous cardiac output (PiCCO or PAC). Measure SvO2 or ScvO2. Exclude abdominal compartment syndrome.


•    Optimise ventilation. Exclude pneumothorax. Probably needs more PEEP after some volume. Minimise airway prtessures, limit tidal volume, tolerate hypercarbia (though concerned about pH < 7!!!)


•    Rationalise inotropes. Stop adrenaline, use noradrenaline as required


•    Emergency management of hyperkalaemia with calcium, bicarbonate, insulin, dextrose and then haemodialysis!


•    Urgent CRRT – for both potassium and acidosis use of hemosol buffer


•    Broad spectrum IV antibiotics (rational answer required)

Discussion

Analysis of the biochemistry:

  • Life-threatening hyperkalemia
  • Acute renal failure

Analysis of the haematology:

  • Thrombocytopenia

Analysis of the ABG:

  • Severe hypoxia
  • High anion gap metabolic acidosis with failure of respiratory compensation (pCOshould be about 25mmHg) - thus, a respiratory acidosis is also present.
  • The anion gap is (138) - (104 + 11) = 23, or 30.1 when calculated with potassium. It is not clear where the college got their value of 33 from.
  • The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (23 - 12) / (24 - 11) = 0.84, giving you the impression that there is some non-anion gap acidosis mixed in with the HAGMA. 
     
  • The lactate is 13.  Notably, the college forcefully points out that the lactate of 13 is insufficient to explain the entire rise in the anion gap. This could be argued. It must be remembered that the lactate does not need to account for all of the calculated 23 mmol/L of the anion gap.  Depending on the laboratory and the anion gap equation which you decided to use (sans or avec potassium), your acceptable standard anion gap could be 12 or 16, and this scenario's anion gap could be 23 or 30 (...or 33?). Ergo, the anion gap has risen by some value in the low teens (let's say 10 to 14). Therefore, the lactate accounts for almost all of the anion gap increase, with only maybe 1 mmol/L remaining unaccounted for. Given that the college do not follow on with any additional suggestions as to the origin of these mysterious anions, it is unclear where they were going with their "NOT adequately explained" statement, or how it factored into their marking rubric.

Causes of the lactic acidosis in this case:

  • Increased production:
    • Hypovolemia and poor tissue perfusion
    • Cardiac injury and cardiogenic shock
    • Sepsis
    • Hypoxia
    • Use of adrenaline
    • Massive rhabdomyolysis
    • Gut ischaemia and abdominal compartment syndrome
    • Toxicity due to mitochondrial toxins
  • Decreased clearance
    • Hepatic injury, ischaemic hepatitis or pre-existing hepatic disease
    • Failure of renal clearance (with lactate above 10mmol/L, renal clearance begins to play a role)

Management priorities:

Something like this benefits from a structured approach.

Airway:

  • Exclude acute airway obstruction
  • Ensure the ETT is well positioned (not in the right main bronchus)
  • Ensure ETT is not kinked and not semiobstructed with secretions or blood, and that it is of an appropriate diameter for this patient (CO2 clearance could be impaired)

Breathing:

  • Exclude tension pneumothorax by clinical examination
  • Exclude more minor pneumothorax with CXR or bedside ultrasonography
  • Increase PEEP to 12
  • Increase I:E ratio to 1:1.5 or 1:1 if the EtCO2 trace does not demonstrate an obstructive pattern (otherwise, hypercapnea could be exacerbated)

Circulation:

  • Exclude cardiac tamponade with bedside TTE
  • Assess fluid responsiveness by static or dynamic manoeuvres; administer volume
  • Assess cardiac output by combination of physical examination, measured variables (PAC or PiCCO) and surrogate measures (ScvO2, A-V CO2 difference)
  • Wean β-2 agonist medications to minimise pharmacological causes of lactate excess. Move on to pure α-1 agonists in pursuit of a normal MAP.

Disability/neurology is not a matter of priority at present.

Electrolyte derangement however is.

  • Administer sodium bicarbonate to replenish buffer systems, correct pH to improve catecholamine efficacy and at the same time shift potassium into the intracellular compartment
  • Administer calcium gluconate to stabilise excitable tissues and prevent arrhythmia
  • Consider insulin and dextrose
  • CVVHDF is indicated:
    • Without renal clearance, dialysis may be the only option to remove the potassium from this organism. One may consider calcium resonium resin if the GI tract is working.
    • In any case, given the history, there is likely massive rhabodomyolysis, and CVVHDF is indicated for this alone.
  • The college also recommends broad spectrum antibiotics. Sepsis is not excluded, so a broad spectrum beta lactam like piperacillin/tazobactam would be a sensible choice.
 

References

Question 15.2 - 2009, Paper 2

A 41 year old man is admitted to your Emergency Department, unconscious, with the first set of blood results. The second set of blood gases are taken 1 hour later.

Parameter

Initial values

1 hour later

Normal range

pH

7.05*

7.35

7.35 – 7.45

PaCO2

34 mmHg (4.6 kPa)

39 mmHg (5.2 kPa)

35 – 45 (4.7-6.0 kPa)

PaO2

203 mmHg (33.6
kPa)

94 mmHg (12.5
kPa)

75 – 98 (10.0-13.0 kPa)

Actual
bicarbonate

9 mmol/l*

21 mmol/l

22 – 26

Sodium

137 mmol/l

134 –145

Potassium

4.2 mmol/l

3.5 – 5.1

Glucose*

11.2 mmol/l

4 – 6

Ionised
Calcium

1.21 mmol/l

1.15 – 1.35

Chloride

105 mmol/L

95 – 105

a)          Describe the initial acid-base disturbance.

b)         List 3 clinical scenarios which may produce such a pattern of arterial blood gas derangement?

College Answer

a)          Describe the initial acid-base disturbance.

The initial acid-base disturbance is a mixed metabolic and respiratory acidosis with a raised anion gap.

b)         List 3 clinical scenarios which may produce such a pattern of arterial blood gas derangement?

Seizures
Resuscitated cardiac arrest
Near drowning
Near hanging

Discussion

Let us dissect these initial results systematically.
 

  1. The A-a gradient cannot be calculated - the FiO2 is not supplied
  2. There is acidaemia
  3. The PaCO2 is vaguely compensatory
  4. The SBE is not supplied, but the bicarbonate is 9 , suggesting a severe metabolic acidosis
  5. The respiratory compensation is inadequate - the expected PaCO2(9 × 1.5) + 8 = 21.5mmHg, and thus there is also a respiratory acidosis
  6. The anion gap is raised: (137) - (105 + 9) = 23, or 27.2 when calculated with potassium. The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (23 - 12) / (24 - 9) = 0.73, suggesting that there is a mixed high and normal anion gap metabolic acidosis. 

In the subsequent gas, the acidosis is almost completely corrected- and it only took one hour.

What could cause this sort of picture?

Well.

Whatever the extra anion was, it has either been buffered well, or it has been eliminated in some way, or it has been metabolised.

Thus, the following things may have happened:

  • The patient received some IV bicarbonate
  • The anion was lactate and virtually all of it has been metabolised; that means the cause was reversible, and has been reversed.
    • Circulatory failure (eg. cardiac arrest, tension pneumothoroax, cardiac tamponade)
    • Hypoxia (asphyxiation of some sort, be it drowning, hanging, etc)
    • Seizures
 

References

Phypers, Barrie, and JM Tom Pierce. "Lactate physiology in health and disease." Continuing Education in Anaesthesia, Critical Care & Pain 6.3 (2006): 128-132.

Question 15.3 - 2009, Paper 2

A 48 year old diabetic with a history of alcohol abuse is admitted with abdominal pain and the following results:

Parameter

Value

Normal range

pH*

6.87

7.35 - 7.45

PaCO2*

8 mmHg (1.1 kPa)

35 - 45 (4.7-6.0 kPa)

PaO2

149 mmHg (20 kPa)

75 - 98 (10.0-13.0 kPa)

Actual bicarbonate*

1.4 mmol/l

22 - 26

Lactate*

16 mmol/l

<2

Sodium

142 mmol/l

134 -145

Potassium

4.7 mmol/l

3.5 - 5.1

Chloride*

107 mmol/L

95 - 105

Urea*

14 mmol/l

3.4 - 8.9

Creatinine*

170 micromol/L

60 - 110

AST*

60

<40 U/L

ALT*

70

<40 U/L

LDH*

1400

50 - 150 U/L

Total bilirubin

20 micromol/L

4 - 25

Glucose*

6.5 mmol/l

4 - 6

Serum osmolality*

314 mOsm/kg

275 - 295

a) Give the three most likely diagnoses.

b) List two additional investigations that you would perform based on the above information.

College Answer

a) Give the three most likely diagnoses.

Diagnoses: 3 ischaemic bowel, 2 metformin induced lactic acidosis, thiamine deficiency, pancreatitis

b) List two additional investigations that you would perform based on the above information.

Two of the following investigations: Diagnostic laparoscopy or laparotomy, CT
abdomen, red cell transketolase, lipase

Discussion

This question is identical to Question 21.2 from the second paper of 2009, and Question 26.4 from the second paper of 2013 . The answer to the latter contains a comprehensive discussion.

 

References

Question 24 - 2010, Paper 1

A 33 year old female presented with high fever and abdominal pain. She has Gram negative bacteraemia and septic shock. The following is data from a blood gas analysis:

Test

Value

Normal Range

Barometric pressure

760 mm Hg

FiO2

0.3

pH

7.43

pO2

107 mm Hg

pCO2

23 mm Hg

HCO3 *

15 mmol/L

(24 – 26)

Standard base excess*

- 8.6 mmol/L

(-2.0 – 2.0)

Lactate*

23.0 mmol/L

(0.2 – 2.5)

Sodium*

147 mmol/L

(135 –145)

Potassium*

6.7 mmol/L

(3.2 – 4.5)

Chloride*

95 mmol/L

(100 –110)

24.1.   List the acid-base abnormalities.

24.2.   What are the causes of elevated plasma lactate in sepsis?

24.3.   Name three (3) drugs (each from a different class of drugs) which result in plasma hyperlactaemia.

24.4.   List two (2) inborn errors of metabolism associated with lactic acidosis.

College Answer

24.1.   List the acid-base abnormalities.

•    High anion gap metabolic acidosis with raised lactate
•    Metabolic alkalosis ( Delta BE < Delta AG)
•    Respiratory alkalosis

24.2.   What are the causes of elevated plasma lactate in sepsis?

•    Circulatory failure due to hypotension and hypoxia
•    Microvascular shunting and mitochondrial failure (cytopathic hypoxia)
•    Use of adrenaline as an inotrope
•    Inhibition of pyruvate dehydrogenase (PDH) by endotoxin.

24.3.   Name three (3) drugs (each from a different class of drugs) which result in plasma hyperlactaemia.

•          Catecholamines
•         Metformin / Phenformin
•          Alcohols
•         Cyanide, nitroprusside
•          Salicylates
•         Lactate containing solutions – HRL, dialysates

24.4.   List two (2) inborn errors of metabolism associated with lactic acidosis.

•  Glucose 6 phosphatase deficiency
•  Fructose 1,6 diphosphatase deficiency
•  Pyruvate carboxylase deficiency
•  Deficiency of enzymes of oxidative phsophorylation

Discussion

The actual ABG itself and the attached patient history are identical to Question 22.2 from the second paper of 2011, and Question 18 from the first paper of 2007.

Generally, this question is frequently repeated, though the exact wording changes.
Question 6.4 from the first paper of 2013 contains a detailed discussion of the answer.

Let us dissect these results systematically.

  1. Yes, the A-a gradient is raised: 
    (0.3 x 713) - 28.8 = 185.1, thus the A-a difference is 195.5-107 = 78.1
  2. There is no acidaemia.
  3. The PaCO2 is compensatory
  4. The SBE is -8.6, suggesting a severe metabolic acidosis
  5. The respiratory compensation is excessive- the expected PaCO2(15 × 1.5) + 8 = 30.3mmHg, and thus there is also a respiratory alkalosis.
  6. The anion gap is raised:
     (147) - (95  + 15) = 37, or 43.7 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (37 - 12) / (24 - 15) = 2.77
    This delta ratio suggests that there is a high anion gap metabolic acidosis coexisting with a metabolic alkalosis.
     

24.1. List the acid-base abnormalities.

  • Respiratory alkalosis
  • High anion gap metabolic acidosis
  • Metabolic alkalosis

24.2. What are the causes of elevated plasma lactate in sepsis?

Copying directly from Question 22.2:

  • Tissue hypoperfusion and hypoxia
  • Use of adrenaline (increased glycolytic flux)
  • Down regulation of pyruvate dehydrogenase by inflammatory mediators
  • Underlying ischaemic tissue
  • Microvascular shunting
  • Sepsis-associated cardiomyopathy

It is interesting to note that though these two questions are identical, the answers are not.

24.3. Name three (3) drugs (each from a different class of drugs) which result in plasma hyperlactaemia.

  • Metformin
  • Isoniazid
  • Iron
  • Toxic alcohols
  • Isoniazid
  • Cyanide
  • Salicylates
  • Catecholamines

24.4. List two (2) inborn errors of metabolism associated with lactic acidosis.

These are discussed in (slightly) greated detail in the chapter on the inherited defects of lactate metabolism. The full list is extensive; the college asks for only two.

The sleep-deprived candidate is likely to remember only glucose-6-phosphatase deficiency. "Deficiency of enzymes of oxidative phsophorylation" is a good all-encompassing statement which is general but still accurate.

References

Christopher, Rita, and Bindu P. Sankaran. "An insight into the biochemistry of inborn errors of metabolism for a clinical neurologist." Annals of Indian Academy of Neurology 11.2 (2008): 68.

 

DiMauro S, Schon EA. Mitochondrial respiratory-chain diseases. N Engl J Med 2003;348(26):2656–68.

 

D C Gore, F Jahoor, J M Hibbert, and E J DeMaria Lactic acidosis during sepsis is related to increased pyruvate production, not deficits in tissue oxygen availability. Ann Surg. 1996 July; 224(1): 97–102.

Question 19 - 2010, Paper 2

A 56 year old, homeless man was admitted to the Emergency Department with clinical features suggestive of a bowel obstruction.  As he is confused, it is not possible to elicit a clear history.

The first set of blood tests show:

Test

Value

Normal Range

Sodium

137 mmol/L

(137 – 145)

Potassium

4.0 mmol/L

(3.1 – 4.2)

Chloride*

98 mmol/L

(101 – 109)

Bicarbonate*

15 mmol/L

(22 – 32)

Glucose*

48 mmol/L

(4.0 – 6.0)

Urea*

18 mmol/L

(3.0 – 8.0)

Creatinine*

0.2 mmol/L

(0.05 – 0.12)

a)  Outline the possible causes of his metabolic acidosis.

b)  What is the corrected serum sodium?

c)  Outline your approach to the correction of his metabolic abnormalities.

d) List the possible complications of this condition and its treatment.

College Answer

a)  Outline the possible causes of his metabolic acidosis.

High anion gap metabolic acidosis

Lactic acidosis 
•    Severe dehydration from osmotic diuresis from hyperglycaemia.
•    Ischaemic bowel
•     Sepsis
•    Metformin (if known type 2 diabetes)

Keto-acidosis 
•  Diabetic (unlikely to be first presentation at 56 yrs with type I diabetes)
•  Alcoholic keto-acidosis (possible although sugar too high)
•  Starvation keto-acidosis (possible although sugar too high)

Toxins

Salicyates, methanol, ethylene glycol,

Renal Failure

b)  What is the corrected serum sodium?

Corrected Sodium= Measured sodium + glucose/4 (Credit was given to people using a range of different formulae) approximately =149 mmol/L.

c)  Outline your approach to the correction of his metabolic abnormalities.

Fluid replacement:
Generally Normal Saline/Hartmanns solution, even if hypernatraemia present to expand ECF volume rapidly.

After initial restoration of normotension, free water replacement .
Fluid titrated to clinical status- organ perfusion, filling pressures, etc. Elderly patients with likely co-existent cardiac disease need more careful monitoring/less aggressive replacement

•     Insulin
-       Blood glucose can fall rapidly when urine output re-established and dehydration corrected. High risk of hypoglycaemia.
-      Treatment with insulin to decrease the serum osmolality by no greater than
2mosmol/kg/hr and blood glucose by no more than 3-4mmol/hr

•     Electrolytes potassium supplements required. Attention to magnesium and phosphate supplementation also required.

•     Correction of underlying cause (in this case, surgery for bowel obstruction)

d)             List the possible complications of this condition and its treatment.

• Cerebral oedema with rapid correction
• Pre-renal azotaemia & renal failure
•  Shock 
• Hypercoagulable state-  thromboembolic complications- DVT, stroke, AMI
• Fluid overload/congestive  cardiac failure with correction
• Metabolic and electrolyte abnormalities- hypokalaemia,
• hypomagnesaemia,  hypophosphataemia,  hypoglycaemia, hyperchloraemic
(non-anion gap) acidosis (normal saline therapy)
• Infections and sepsis

Discussion

In this question, the candidates are presented with a picture closely resembling a HONK.

The proper calculation of the anion gap is fuddled by the presence of vast quantities of glucose, and thus an inaccurate reported sodium.

Unadjusted, the biochemistry suggests that the anion gap may be significantly raised:

(137 + 4) - (98 + 15) = 28.

However, if we adjust the sodium, we find that it is even worse.

(149 + 4) - (98 + 15) = 40

Thus, the candidate ought to remember that up-adjusting the sodium for hyperosmolar states will only make the anion gap wider.

The delta ratio, calculated from the corrected and uncorrected anion gaps, is either 1.7 or 3.1

(28 - 12) / ( 24 - 15) or (40 - 12) / (24 - 15)

Thus, there is a high anion gap metabolic acidosis which coexists with a metabolic alkalosis.

a) Outline the possible causes of his metabolic acidosis.

The list of differentials provided by the college is comprehensive.

One may divide it into a MUDPILES mnemonic, or organise it by unmeasured anions:

  • Lactate:
    • Hypovolemic shock
    • Sepsis
    • Cardiogenic shock
    • Mitochondial toxicity
    • Thiamine deficiency
    • Biguanide poisoning
  • Toxic metabolites
    • Methanol
    • Ethylene glycol
  • Ketoacids
    • Diabetic ketoacidosis
    • Alcoholic ketoacidosis
    • Starvation ketoacidosis
  • Unmeasured non-volatile metabolic acids
    • Renal failure

b) What is the corrected serum sodium?

The college gave the candidates credit for mentioning a number of formulae.

There are indeed several different ways of calculating the corrected sodium.

They all follow the same trend: Corrected Na+ = measured Na+ + (correction factor)

The correction factor is a matter of debate, and there are several variations:

  • Glucose in mmol/L divided by 4
  • (Glucose in mg/dL - 100) multiplied by 0.016
  • (Glucose in mg/dL - 100) multiplied by 0.024

c) Outline your approach to the correction of his metabolic abnormalities.

One would not need to approach this in an algorithmic fashion. It is a question specifically about the metabolic abnormalities, and so one does not need to go on at lengths about securing the airway.

Thus:

  • Correct fluid deficit with fluid resuscitation
  • Correct hyperglycaemia with insulin
    • careful monitioring for hypoglycaemia (the college points out that once the renal function begins to recover, urinary losses of glucose will be rapid)
  • Correct electrolytes by careful monitoring and replacement
  • Correct underlying disorder (bowel obstruction)

d) List the possible complications of this condition and its treatment.

Complications of HONK are discussed in greater detail elsewhere.

In brief, the major ones are listed below:

  • Cardiac arrest
  • Cardiovascular collapse
  • Myocardial infarction
  • Stroke
  • Cerebral oedema and brain injury
  • Venous thrombosis

In addition to these, the college has thrown in infection/sepsis as a complication of bowel obstruction, as well as complication of HONK management (electrolyte bewilderment and fluid overload).

References

Hillier, Teresa A., Robert D. Abbott, and Eugene J. Barrett. "Hyponatremia: evaluating the correction factor for hyperglycemia." The American journal of medicine 106.4 (1999): 399-403.

Roscoe, J. M., et al. "Hyperglycemia-induced hyponatremia: metabolic considerations in calculation of serum sodium depression." Canadian Medical Association Journal 112.4 (1975): 452.

Question 25.2 - 2010, Paper 2

List 3 causes for the following combination  of findings observed on a serum sample.

Test

Value

Normal Range

Measured osmolality*

340 mOsm/kg

(280 – 290)

Sodium

138 mmol/L

(135 – 145)

Potassium

4 mmol/L

(3.5 – 5.0)

Chloride

98 mmol/L

(95 – 105)

Bicarbonate*

15 mmol/L

(22 – 32)

Glucose

6 mmol/L

(4 – 6)

Urea

8 mmol/L

(6 – 8)

College Answer

•    Raised osmolar gap with raised AG
•     Methanol
•    Ethylene glycol
•     Ethanol
•    Lactic acidosis can lead to a raised OG and AG, however, the osmolar gap does not reach the levels seen here.

Discussion

These biochemistry results are provided without any history.

Let us dissect them systematically.

  1. The A-a gradient cannot be calculated
  2. The pH is not supplied
  3. The PaCO2 is not reported
  4. The SBE is not offered, but the bicarbonate is 15, suggetsing a metabolic acidosis.
  5. The respiratory compensation cannot be assessed.
  6. The anion gap is raised:
    (138) - (98  + 15) = 25, or 29 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (25 - 12) / (24 - 15) = 1.44
    This delta ratio suggests that there is a pure high anion gap metabolic acidosis here.
  7. The osmolar gap is raised: 340 - (2 × 138 + 6 + 8) = 50

Thus, this high anion gap metabolic acidosis is also associated with a raised osmolar gap.

Most likely differentials:

  • Toxic alcohol intoxication, which includes ethanol intoxication. This is probably the only commonly seen cause of such a massively raised osmolar gap associated with a high anion gap metabolic acidosis.

Less likely differentials (osmolar gap is probably a bit too high for these to be realistic differentials):

References

Jacobsen, Dag, et al. "Anion and osmolal gaps in the diagnosis of methanol and ethylene glycol poisoning." Acta Medica Scandinavica 212.1‐2 (1982): 17-20.

Question 25.3 - 2010, Paper 2

List 2 causes for the following combination  of findings observed on a serum sample.

Test

Value

Normal Range

Measured osmolality*

310 mOsm/L

(280 – 290)

Sodium*

125 mmol/L

(135 – 145)

Potassium

4 mmol/L

(3.5 – 5.0)

Chloride

98 mmol/L

(95 – 105)

Bicarbonate*

21 mmol/L

(22 – 32)

Glucose

6 mmol/L

(4 – 6)

Urea

8 mmol/L

(6 – 8)

 

College Answer

•    Raised osmolar gap with normal AG
•     Mannitol
•     Glycine
•     Ethanol

Discussion

These biochemistry results are provided without any history.

Let us dissect them systematically.

  1. The A-a gradient cannot be calculated
  2. The pH is not supplied
  3. The PaCO2 is not reported
  4. The SBE is not offered, but the bicarbonate is 21, suggesting a trend towards metabolic acidosis.
  5. The respiratory compensation cannot be assessed.
  6. The anion gap is normal:
     (125) - (98  + 21) = 6, or 10 when calculated with potassium
  7. The osmolar gap is raised: 310 - (2 × 125 + 6 + 8) = 46

So, this is a hyperosmolar state without metabolic acidosis. It stands to reason that the extra osmoles are probably not participating in any sort of metabolism.

This sort of picture is consistent with the following scenarios:

  • Mannitol therapy
  • Glycine (post-TURP syndrome)
  • Alcohol intoxication (early in the night)

Glucose and urea may contribute in other scenarios, but in this set of biochemistry results they are represented by normal values.

The possible contributors to the hyperosmolarity are discussed briefly in the chapter on hyperosmolar hypernatremia.

 

References

Yun JJ, Cheong I. Mannitol-induced hyperosmolal hyponatraemia. Intern Med J. 2008 Jan;38(1):73.

Rothenberg, David M., Arnold S. Berns, and Anthony D. Ivankovich. "Isotonic hyponatremia following transurethral prostate resection." Journal of clinical anesthesia 2.1 (1990): 48-53.

 

Liamis, George L., et al. "Mechanisms of hyponatraemia in alcohol patients."Alcohol and Alcoholism 35.6 (2000): 612-616.

Taivainen, Hanna, et al. "Role of plasma vasopressin in changes of water balance accompanying acute alcohol intoxication." Alcoholism: Clinical and Experimental Research 19.3 (1995): 759-762.

Question 6.1 - 2011, Paper 1

This blood gas report was taken from a lady hospitalised for recurrent urinary tract infections. She was transferred to the ICU because of nosocomial pneumonia.

Test

Value

Normal Range

FiO2

0.3

pH

7.53

7.35 – 7.45

pCO2*

31 mmHg (4  kPa)

35 – 45  (4.6 – 5.9)

pO2

83.7 mmHg (11 kPa)

80 – 110  (10.5 – 14.5)

Bicarbonate

25 mmol/L

24 – 32

Standard Base Excess*

3.3 mmol/L

-2.0 – +2.0

a)  Comment on the acid-base status.

b)  List 2 likely causes of the acid-base derangement in this patient.

College Answer

a)  Comment on the acid-base status.

Mixed respiratory and metabolic alkalosis

b)  List 2 likely causes of the acid-base derangement in this patient.

Respiratory alkalosis from the hyperventilation due to the pneumonia

Metabolic alkalosis from vomiting or diuretic use

Discussion

 This question is identical to Question 6.1  from the first paper of 2013.

References

Question 6.2 - 2011, Paper 1

A  40  year  old  70  kg  male  has  gram  negative  sepsis  and  has  developed bilateral pulmonary infiltrates. The following are data from blood gas analysis.

Test

Value

Normal Range

FiO2

0.5

pH*

7.31

7.35 – 7.45

pCO2*

31 mmHg (4 kPa)

35 – 45  (4.6 – 5.9)

pO2

110 mmHg (14.5 kPa)

80 – 110  (10.5 – 14.5)

Bicarbonate*

15.1 mmol/L

24 – 32

Standard Base Excess*

-10.0 mmol/L

-2.0 – +2.0

a)  Could this blood gas be consistent with the definition of acute respiratory distress syndrome (ARDS)? Give your reasoning.

b)  What dose of sodium bicarbonate (in mmol) would be required to reverse the metabolic acidosis? Show your calculation method.

College Answer

a)  Could this blood gas be consistent with the definition of acute respiratory distress syndrome (ARDS)? Give your reasoning.

No. The P/F ratio is 220. By definition, the problem would be acute lung injury rather that ARDS at this stage.

b)  What dose of sodium bicarbonate (in mmol) would be required to reverse the metabolic acidosis? Show your calculation method.

Dose sodium bicarbonate = Wt (kg) x 0.3 x -SBE = 70 x 0.3 x 10 = 210 mmol

Discussion

Unlike the majority of these questions about ABGs, this one does not require indepth interpretation of the acid-base disturbance.

The first question refers to the now-extinct definition of ARDS, which is distinct from the new definition of ARDS. The issues surrounding ARDS classification are discussed in full elsewhere, and I will not rant about this extensively, except to mention the following ranges of the PaO2/FiO2 ratio:

  • 300-200 = "mild" ARDS, ~ 27% mortality
  • 200-100 = "moderate" ARDS ~32% mortality
  • under 100 = "Severe" ARDS, ~ 45% mortality

This patient has an P/F ratio which is 110/0.5 = 220; thus the patient falls into a "mild" ARDS category, or "Acute Lung Injury" according to the old definition. The new ARDS definition has replaced the old as of 2012, about 1 year after the candidates were exposed to this question paper.

Now, as for the bicarbonate:

There are actually several methods of estimating the amount of bicarbonate required to titrate somebody's body fluids back to normal pH. They are all equally inaccurate. Assumptions are made about the volume of distribution of bicarbonate, which is about 50% of body weight at normal pH and about 100% at a low pH. These things are discussed in greater detail in a distant chapter where I attempted to explain to myself the physiological response to an infusion of sodium bicarbonate.

For example, the following equations give an answer as bicarbonate dose in mmol.

  • body weight in kg × 1
  • body weight × 0.3 × SBE
  • body weight × 0.3 × (desired HCO3- - measured HCO3-)
  • body weight × ( 0.4 + 2.6 / measured HCO3-)

References

Reversal of metabolic acidosis with bicarbonate, and the various equation used to calculate it, is discussed at great length in a 2008 article by Sabatini and Kurtzman.

The old definition of ARDS and ALI is described in this seminal paper:

Bernard G, Artigas A, Brigham K, Carlet J, Falke K, Hudson L, Lamy M, Legall J, Morris A, Spragg R (1994). "The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination". Am J Respir Crit Care Med 149 (3 Pt 1): 818–24

However, it is not available as free full text.

Though the JAMA site is still paywalled, The Sociedad Uruguaya de Neonatologia Y Pediatria Intensiva have mirrored the Berlin Definition statement article for your viewing pleasure:

CV. Marco Ranieri, MD (2012). "The ARDS Definition Task Force*. Acute Respiratory Distress Syndrome: The Berlin Definition". JAMA 307 (23): 2526-2533.

The new definition is discussed here; it was revised by the ARDS Definition Task Force: "Acute Respiratory Distress Syndrome." Jama307.23 (2012): 2526-2533.

Schwartz, William B., and Arnold S. Relman. "A Critique of the Parameters Used in the Evaluation of Acid-Base Disorders: Whole-Blood Buffer Base and Standard Bicarbonate Compared with Blood pH and Plasma Bicarbonate Concentration." New England Journal of Medicine 268.25 (1963): 1382-1388.

Sabatini, Sandra, and Neil A. Kurtzman. "Bicarbonate therapy in severe metabolic acidosis." Journal of the American Society of Nephrology 20.4 (2009): 692-695.

Garella, Serafino, Clare L. Dana, and Joseph A. Chazan. "Severity of metabolic acidosis as a determinant of bicarbonate requirements." New England Journal of Medicine 289.3 (1973): 121-126.

Fernandez, Pedro C., Raphael M. Cohen, and George M. Feldman. "The concept of bicarbonate distribution space: the crucial role of body buffers."Kidney international 36.5 (1989): 747.

Question 6.3 - 2011, Paper 1

Following  laparotomy  for haemoperitoneum,  a patient  is transferred  to ICU.
Blood biochemistry  and arterial blood gas analysis on admission  to ICU are as follows:

Test

Value

Normal Range

Sodium*

147 mmol/L

135 – 145

Potassium

3.6 mmol/L

3.2 – 4.5

Chloride*

124 mmol/L

100 – 110

Haemoglobin*

106 G/L

115 – 155

pH

7.32

7.35 – 7.45

pCO2*

32.4 mmHg (4.3 kPa)

35 – 45  (4.6 – 5.9)

pO2*

63 mmHg (8.4 kPa)

80 – 110  (10.5 – 14.5)

Bicarbonate*

16.0 mmol/L

24 – 32

Standard Base Excess*

-9.0 mmol/L

-2.0 – +2.0

a)  Describe the acid-base status.

b)  What is the likely cause of this disturbance?

c)  What is the underlying biochemical mechanism?

College Answer

a)  Describe the acid-base status.
Normal anion gap metabolic acidosis with appropriate respiratory compensation

b)  What is the likely cause of this disturbance?
Resuscitation with large volume saline infusion.

c)  What is the underlying biochemical mechanism?
ECF dilution by fluid with strong ion difference of zero

Discussion

 This question is identical to Question 6.3  from the first paper of 2013.

References

Question 6.4 - 2011, Paper 1

A 33 year old female has gram negative  bacteraemia  and septic shock. The following are data from blood gas analysis.

Test

Value

Normal Range

Barometric pressure

760 mmHg (100 kPa)

FiO2

0.3

pH

7.43

7.35 – 7.45

pCO2*

23 mmHg (3.1 kPa)

35 – 45  (4.6 – 5.9)

pO2

107 mmHg (14.3 kPa)

80 – 110  (10.5 – 14.5)

Bicarbonate*

15 mmol/L

24 – 32

Standard Base Excess*

-8.6 mmol/L

-2.0 – +2.0

Lactate*

23.0 mmol/L

0.2 – 2.5

Sodium*

147 mmol/L

137 – 145

Potassium*

6.7 mmol/L

3.2 – 4.5

Chloride*

95 mmol/L

100 – 110

a)  List the acid-base abnormalities.

College Answer

a)  List the acid-base abnormalities.
Lactic acidosis
Anion gap elevation (37 mEq/L) Metabolic alkalosis
Respiratory alkalosis

Discussion

This question is frequently repeated. A list of duplicates can be found in a chapter on the causes of lactic acidosis in sepsis. Question 6.4 from the first paper of 2013 contains a detailed discussion of the answer.

References

Question 9.2 - 2011, Paper 1

You  are  asked  to  review  a  44  year  old  male  known  epileptic  following  a prolonged  generalised  tonic-clonic  convulsion.     He is  intubated  and ventilated. Arterial blood gas analysis is as follows:

Test

Value

Normal Range

FiO2

0.5

pH*

7.15

7.35 – 7.45

pCO2

35 mmHg (4.6 kPa)

35 – 45 (4.6 – 6)

pO2*

105 mmHg (14 kPa)

75 – 98 (10 – 13)

HCO3-*

10.3 mmol/l

22 – 26

a)  List the abnormalities  on the blood gas and give the most likely cause of each abnormality.

College Answer

a)  List the abnormalities  on the blood gas and give the most likely cause of each abnormality.

•    Metabolic acidosis – lactic acidosis secondary to prolonged seizures
•    Respiratory  acidosis  (or  inadequate  compensation)  –  central  hypoventilation  or inadequate mechanical ventilation
•    Increased A-a gradient  - aspiration pneumonia

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high:
    PAO2 = (0.5 × 713) - (35 × 1.25) = 312.75
    Thus, A-a = ( 312.75 - 105) = 207.75mmHg.
    In fact, the PaO2/FiO2 ratio is (105/0.5) = 210, which puts this man's hypoxia in a "mild ARDS" category by the 2012 Berlin definition.
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is not offered, but the bicarbonate is low, suggesting a severe metabolic acidosis
  5. The respiratory compensation is inadequate - the expected PaCO2 = (10.3 × 1.5) + 8 = 23.5 mmHg, and thus there is also a respiratory acidosis
  6. The anion gap cannot be calculated.

The college suggests the following explanations for this gas:

  • Hypoxia = aspiration
  • Hypercapnea = obtundation
  • Metabolic acidosis = seizure-associated rise in lactate.

This explanation is certainly within reason. One could even get into a discussion about MELAS. Often in the postictal state there is still appropriate respiratory compensation for the lactic acidosis, with most postictal patients averaging a PaCO2 around 17mmHg in a 1977 study of post-seizure lactic acidosis. However, postictal hypopnoea is a known cause of respiratory acidosis after a seizure, and may be a factor in SUDEP - Sudden Unexplained Death in Epilepsy.

To consider alternative explanations, this mixed acid-base disturbance can also be accounted for by the complications of toxic alcohol ingestion, a hypoglycaemic episode, opiate overdose, and numerous others.

References

Pavlakis, Steven G., et al. "Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome." Annals of neurology 16.4 (1984): 481-488.

Orringer, Carl E., et al. "Natural history of lactic acidosis after grand-mal seizures: a model for the study of an anion-gap acidosis not associated with hyperkalemia." New England Journal of Medicine 297.15 (1977): 796-799.

Bateman, Lisa M., Mark Spitz, and Masud Seyal. "Ictal hypoventilation contributes to cardiac arrhythmia and SUDEP: Report on two deaths in video‐EEG–monitored patients." Epilepsia 51.5 (2010): 916-920.

Question 18.2 - 2011, Paper 1

A 35-year-old female with a history of poorly controlled hypertension presents with paraesthesia and weakness. Her blood results are shown below:

Patient value

Normal range

Sodium

145 mmol/L

135 – 145

Potassium

1.8 mmol/L

3.5 – 5.0

Chloride

85 mmol/L

97 – 109

Bicarbonate

40 mmol/L

24 – 32

Urea

3.4 mmol/L

3.0 – 8.0

Creatinine

80 µmol/L

70 – 110

Arterial blood gases

Patient value

Normal range

pH

7.56

7.35 – 7.45

pO2

85 mmHg           (11.3 kPa)

80 – 110 mmHg      (10.5 – 14.5 kPa)

pCO2

46 mmHg           (6.1 kPa)

35 – 45 mmHg        (4.6 – 5.9 kPa)

Bicarbonate

40 mmol/L

23 – 33

a) Interpret these results

b) List 2 likely diagnoses

c) Give 2 drugs used to treat this condition

d) List 3 other potential causes of these biochemical abnormalities

College Answer

a) Interpret these results

Metabolic alkalosis with partial respiratory compensation and severe hypokalaemia

b) List 2 likely diagnoses

  • Primary  Hyperaldosteronism   most  likely  secondary  to  an  aldosterone  producing adenoma (Conn’s syndrome – 50-60%) or adrenal hyperplasia (40-50%)
  • Licorice ingestion
  • Liddle’s syndrome
  • Excessive diuretic use

c) Give 2 drugs used to treat this condition

  • Aldosterone antagonist (spirinolactone or eplerenone)
  • Amiloride

d) List 3 other potential causes of these biochemical abnormalities

1/ laxative abuse
2/vomiting
3/diarrhoea
3/cushings and ACTH tumors
5/ primary metabolic alkalosis

Discussion

Let us dissect this ABG according to the classical rules.

With a bicarbonate level of 40, the PCO2 should be (0.7 × 40 + 20) - or about 48, ± 5mmHg.

The gas we get from the college gives us a PCO2 of 46 mmHg, which is within the range of error.

I could call that a compensated disorder, but - lets be fair - its 2mmHg lower than the predicted value, so the savage ABG purist would be forced to label this as "partial" compensation.

The only other (massive) abnormality is the almost-unsurvivable K+ level (1.8mmol/L).

What are the causes of metabolic alkalosis, then? Particularly with such hypokalemia?

Answers b) and d) essentially ask the candidate to spew forth a torrent of differentials. Its a game of "how many causes of metabolic alkalosis can you think of in under 3 minutes". Judging by the pass rate, a fair few of us are rather good at this.

Even though this list of differentials is discussed in another chapter (Causes of metabolic alkalosis), I reproduce it here in order to simplify revision.

Differential Diagnosis for the Causes of Metabolic Alkalosis

Chloride depletion

  • Gastric losses by vomiting or drainage
  • Diuretics:
    • loop diuretics
    • thiazides
  • diarrhoea
  • posthypercapneic state (chronic compensatory renal loss)
  • dietary chloride deprivation
  • gastrocystoplasty
  • cystic fibrosis (loss due to high sweat chloride content)

Bicarbonate excess (real or apparent)

  • Iatrogenic alkalinisation
  • Recovery from starvation
  • Hypoalbuminemia

Potassium depletion

  • Primary hyperaldosteronism
  • Mineralocorticoid oversupplementation
  • Licorice (glycyrrhizic acid)
  • β-lactam antibiotics
  • Liddle syndrome
  • Severe hypertension
  • Bartter and Gitelman syndromes
  • Laxative abuse
  • Clay ingestion

Calcium excess

  • Hypercalcemia of malignancy
  • Milk-alkali syndrome

Lastly, management is asked about. It requires little imagination to answer "block the aldosterone excess", and a receptor blocker such as spironolactone is a convenient and reasonably safe means of doing so.

References

Tripathy, Swagata. "Extreme metabolic alkalosis in intensive care." Indian journal of critical care medicine: peer-reviewed, official publication of Indian Society of Critical Care Medicine 13.4 (2009): 217.

Galla, John H. "Metabolic alkalosis." Journal of the American Society of Nephrology 11.2 (2000): 369-375.

Question 22 - 2011, Paper 1

A 45 year old man was admitted to the intensive care unit after sustaining 40% BSA burns  in a house  fire.  He was  transported  initially  to a local  hospital where initial resuscitation  was commenced  including  mechanical  ventilation for suspected inhalational injury.  On arrival in your ICU an arterial blood gas was taken which is shown below:

Patient value

Normal range

pH

7.14

pCO2

34 mmHg         (4.5 kPa)

pO2

195 mmHg

Bicarbonate

8 mmol/L

24 – 32

Standard Base Excess

-16.1 mmol/L

-2.0 – +2.0

Chloride

120 mmol/L

98 – 108

Sodium

145 mmol/L

133 – 145

Potassium

4.8 mmol/L

3.2 – 4.5

Haemoglobin

180 g/L

115 – 160

Arterial Lactate

3.8 mmol/L

< 1.5

a)  List four potential contributing causes of the metabolic derangement

b)  How would you classify the acid base derangement and explain your reasoning?

c) The serum albumin is 18g/L. Outline how would this affect the anion gap.

d)  Whilst on your ward round the RMO asks your opinion on the Stewart approach to acid base physiology. List the 3 independent variables that comprise this approach

College Answer

a)  List four potential contributing causes of the metabolic derangement

•    Shock/Underesuscitation/hypovolaemia (elevated Hb and Lactate)
•    Normal (0.9%) Saline fluid resuscitation
•    Carbon monoxide poisoning
•    Cyanide toxicity from smoke inhalation (elevated anion gap acidosis)
•    Other   missed   injuries   e.g.  abdominal   trauma,   bleeding   etc  leading   to  hypo perfusion/shock
•    Potential concurrent ingestions e.g. methanol, ethylene glycol

b)  How would you classify the acid base derangement and explain your reasoning?

•    Mixed metabolic acidosis

(Note: CO2 is also high for pH but less relevant because patient on IPPV)
Delta ratio indicates a greater fall in [HCO3-] than expected given increase in AG. This can be explained  by a mixed metabolic  acidosis,  i.e. a combined high anion
gap and normal anion gap acidosis.

c) The serum albumin is 18g/L. Outline how would this affect the anion gap.

•    The   plasma   proteins   are   the   major   source   of   unmeasured   anions.   Hypo albuminemia may mask an increased concentration  of gap anions by lowering the value of the anion gap. Adjustment of the anion gap can be made by the application of correction factors (see Figge et al, CCM 1998).

d)  Whilst on your ward round the RMO asks your opinion on the Stewart approach to acid base physiology. List the 3 independent variables that comprise this approach

Strong ion difference
Partial CO2 tension
Total concentration of weak acid (ATOT)

Discussion

Logically, (b) is the question one ought to answer first, in order to answer (a).

Thus: a systematic approach:

  1. The A-a gradient cannot be calculated; all that can be said is that this gentleman is not hypoxic
  2. There is acidaemia
  3. The PaCO2 is compensatory (34mmHg)
  4. The SBE is -16.1, suggesting a severe metabolic acidosis
  5. The respiratory compensation is inadequate - the expected PaCO2( 8 × 1.5) + 8 = 20mmHg, and thus there is also a respiratory acidosis
  6. The anion gap is raised:
    (145) - (120 + 8) = 17, or 21.8 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (17 - 12) / (24 - 8) = 0.31
    This delta ratio suggests that there is a mixed high anion gap and normal anion gap metabolic acidosis here.

 If we adjust the anion gap to compensate for the low albumin (which is discussed later), the "normal" anion gap value ends up being about 6.5, which means the delta ratio is in fact 0.65. 

Now, for question (a): the following are potential causes of a mixed metabolic acidosis in a severe burns patient:

  • Shock due to hypovolemia (hemoconcentration is apparent from the high Hb level)
  • Shock due to sepsis
  • High lactate due to carbon monoxide poisoning
  • High lactate due to cyanide poisoning

c) Albumin is a negatively charged protein, and thus it contributes to the anion gap in solution. Indeed for every 4 grams per litre of albumin, the "normal" anion gap value changes by 1. Thus, if we assume that the "normal" albumin value is about 40, this patient has an "albumin deficit" of 22g/L, and the normal value for anion gap should actually be 6.5 (12 - 22/4).

d) The college asks the candidate to list the three independent variables of Stewart's interpretation of acid-base physiology.

  • Strong ion difference
  • Partial CO2 tension
  • Total concentration of weak acid (ATOT)

The Stewart approach can be found heavily marketed at acid-base.org. The original paper, describing the dependent and independent variables, can be found here but is available as an abstract only. Fortunately, the acid-base.org people have published Stewart's original book online, for free.

References

Figge, James, et al. "Anion gap and hypoalbuminemia." Critical care medicine26.11 (1998): 1807-1810.

Stewart, Peter A. "Independent and dependent variables of acid-base control." Respiration physiology 33.1 (1978): 9-26.

Question 3.1 - 2011, Paper 2

A 70-year-old, 42kg female with chronic renal failure, Type 2 diabetes and a history of alcohol abuse was admitted for management of leg ulcers infected with MSSA. Ten days into her admission she became increasingly short of breath and was referred to ICU.

Parameter Patient value    Normal range
Sodium                                      139 mmol/l 134 – 146
Potassium                        4.4  mmol/l        3.4 – 5.0
Chloride                  115 mmol/l           100 – 110
Urea                           15.3* mmol/l 3.0 – 8.0
Creatinine                 309* umol/l 50 – 120
Glucose                     5.1 mmol/l 3.0 – 5.4
pH                               7.11* 7.35 – 7.45
PCO2                                    13* mmHg (1.7* kPa) 35 – 45 (4.6 – 6.0)
HCO3                                   4* mmol/l 22 – 27
Base excess              -24*                             -2 – +2
Measured osmolality  300 mOsm/kg           280 – 300

a) Describe this acid-base picture

b) Give three possible causes

College Answer

a)
Severe compensated metabolic acidosis with a raised anion gap (~20), normal osmolar gap and delta ratio 0.4 (Some candidates might say that there is both a high AG and normal AG acidosis rather than stating the delta ratio and that is also correct).

b)
Renal failure

Pyroglutamic acidosis (renal and liver dysfunction and possible flucloxacillin and paracetamol exposure) 

Sepsis

Metformin related lactic acidosis
(delta ratio suggests mixed AG and NAG MA or renal failure)

Discussion

This is another one of these "interpret an ABG" questions.

How did they arrive at these answers?

Normal or slightly raised osmolar gap     

= 300 - ((1.86 x 139) + 15.4 + 5.1 + 9) = 12.

High anion gap                                            
The anion gap is (139) - (115 + 4) = 20, or 24.4 when calculated with potassium
 

Delta ratio = 0.4    
 The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, is
(20 - 12) / (24 - 4) = 0.4                                      
 

Thus, this is a high anion gap metabolic acidosis with hyperchloraemia, with normal osmolar gap, and incomplete respiratory compensation.

The MSSA mentioned in question 3.1 is a hint at flucloxacillin exposure, to make you think of pyroglutamic acidosis. Having never heard of pyroglutamic acidosis, I have found this article to explain it to myself. There is also another article here. A local summary of pyroglutamic acidosis is also available.

Pyroglutamic acidosis occurs due to glutathione depletion in patients who receive flucloxacillin or vigabatrin  together with paracetamol. The key feature is loss of feedback inhibition because of glutathione depletion, which results in overproduction of pyroglutamic acid.

References

Wrenn K. The delta gap: an approach to mixed acid-base disorders. Ann Emerg Med 1990 Nov; 19(11) 1310-3.

Dempsey GA Lyall HJ, Corke CF, Scheinkestel CD. Pyroglutamic acidemia: a cause of high anion gap metabolic acidosis. Crit Care Med. 2000Jun;28(6):1803-7.

 

 

 

Question 3.2 - 2011, Paper 2

These results are from the arterial blood gas report of a 41-year-old female ventilated in ICU for three weeks with H1N1 influenza and ARDS

Parameter Patient value     Normal range
FiO2                       0.6  
pH                               7.5* 7.35 – 7.45 
PO2      79.0 mmHg (10.5 kPa)  
PCO2               48.0* mmHg (6.3 kPa)         35 – 45 (4.6 – 6.0)
HCO3                                   36* mmol/L   22 – 27 
Base excess              12* -2.0 – +2.0
Sodium                      138 mmol/L 135 – 145
Potassium                 5.0 mmol/L 3.5 – 5.0
Chloride                     97 mmol/L 95 – 105                 

a) Describe this acid-base picture

b) What is the likely cause of the acid-base disturbance?

College Answer

a)
Metabolic alkalosis
A-a DO2 295

b)
Resolution of respiratory acidosis with delayed correction of metabolic compensation
Diuretic therapy

Discussion

This is another one of these "interpret an ABG" questions.

Widened A-a gradient? yes there is; by the standard equation,

(713 x 0.6) – (48 x 1.25) – (79) =288.8

On FiO2 of 60%, the PaO2 should be about 378.

There is also a metabolic alkalosis with normal chloride and normal potassium. The hint is that this patient has been ventilated for 3 weeks. ARDS ventilation typically involves "permissive hypercapnea", which leads to a gradual renal compensation, with the retention of bicarbonate. As the respiratory acidosis resolves, an alkalaemia develops because the increase in the rate of bicarbonate excretion is delayed.

References

For all your acid-base needs, visit anaesthesiamcq.org

Williamson JC. Acid-base disorders: classification and management strategies. Am Fam Physician 1995 Aug; 52(2) 584-90.  

 

Question 3.3 - 2011, Paper 2

A 26-year-old man with a history of solvent abuse presents to the Emergency Department

Parameter Patient value     Normal range
FiO2 0.4  
pH                               6.94*                           7.35 – 7.45 
PO2                                        140 mmHg  
PCO2                                    17* mmHg               35 – 45 (4.6 – 6.0)          
HCO3                                   4* mmol/L                  22 – 27
Base excess               -28*                             -2.0 – +2.0
Sodium                      127* mmol/L 135 – 145          
Chloride           113* mmol/L              95 – 105
Urinary pH                 7.2                                         4.6 – 8.0               

a) Describe this acid-base picture

b)What is the likely cause of the acid-base disturbance?

College Answer

a) Normal anion gap severe metabolic acidosis with incomplete compensation

b)Renal tubular acidosis Type 1 distal secondary to chronic toluene abuse

Discussion

How did they reach these conclusions?

Let us approach this systematically.

  1. The A-a gradient is slightly raised:
    PAO2 = (0.4 × 713) - (17 × 1.25) = 263.95
    Thus, A-a = ( 263.95 - 140) = 143.95mmHg.
  2. There is severe acidaemia
  3. The PaCO2 is low, suggesting an attempt at compensation
  4. The SBE is -28, suggesting a severe metabolic acidosis
  5. The respiratory compensation is either complete, or there is a mild respiratory acidosis:
    Boston rules: the expected CO2 is (1.5 × 4) + 8 = 14mmHg (plus-minus 3)
    Copenhagen rules: the expected CO2 is (40-SBE) = 12
  6. The anion gap cannot be calculated in the conventional sense, but if you ignore the potassium it ends up being (127 – 113 – 4) = 10.

There is not enough information to calculate the osmolar gap.
This is a normal anion gap severe metabolic acidosis with incomplete compensation.

The solvent abuse mentioned in the question points to toluene.
Toluene toxicity alone would have caused a high anion gap metabolic acidosis (due to accumulation of hippuric acid). However, the hippurate anion is rapidly excreted via the kidneys, whereas the hydrogen ions remains. The RTA due to toluene is a type 1, which is a hyperchloremic hypokalemic acidosis due to a failure to acidify the urine in the distal tubule. Another characteristic feature is the extremely alkaline urinary pH which contrasts with the extremely acidic blood pH; such a situation tends to only occur in the case of a Type 1 (distal) RTA, whereas with the other RTAs the urinary acidification is at least somewhat preserved.

References

For a scenic overview of renal tubular acidosis, I turn to UpToDate.

An even better (free) resource is a beautiful article by Juan Rodríguez Sorianoentitled "Renal Tubular Acidosis: The Clinical Entity" which is available online.

Batlle DC, Sabatini S, Kurtzman NA. On the mechanism of toluene-induced renal tubular acidosis. Nephron. 1988;49(3):210-8.

Unwin RJ, Capasso G,The renal tubular acidoses J R Soc Med. 2001 May; 94(5): 221–225.

Chan JCM, Scheinman JI, Roth KS. Renal Tubular Acidosis Pediatrics in Review Vol.22 No.8 August 2001 2

 

Question 9.1 - 2011, Paper 2

The following arterial blood gas and biochemistry results are from a patient with cardiac and respiratory disease and recent profuse vomiting.

Parameter Patient value    Normal range
 FiO2                                0.4  
  pH                                        7.5                               7.35 – 7.45        
 PaO2                                         58.0 mmHg (7.6 kPa)          
 PaCO2                                  47* mmHg (6.2 kPa)           35 – 45 (4.6 – 6.0)     
 HCO3                                      34.8* mmol/l                22 – 27    
Base Excess               10.2*                  -2.0 – +2.0         
Sodium                        137 mmol/l                  135 – 145               
 Potassium                        2.5* mmol/l                  3.5 – 5.0                
 Chloride                       92* mmol/l                  95 – 105                     

a) Describe the acid-base disturbance(s)

b) List the potential causes of the acid-base abnormalities in this patient

College Answer

a)
Metabolic alkalosis with respiratory compensation 

b)
Diuretic therapy 
Steroid therapy 
Vomiting from gastric outlet obstruction 
Post hypercapnoeic alkalosis

 

Discussion

This question is a fairly straightforward ABG interpretation exercise.

I could add nothing more to these answers. The question plainly states there has been profuse vomiting.

Let us dissect these results systematically.

  1. The A-a gradient is high:
    PAO2 = (0.4 × 713) - (47 × 1.25) = 155.05
    Thus, A-a = (155.05 - 58) = 97.05mmHg.
  2. There is alkalaemia
  3. The PaCO2 is compensatory
  4. The SBE is 10.2, suggesting a metabolic alkalosis
  5. The respiratory compensation is reasonable - the expected PaCO2(0.7 × 34.8) + 20 = 44.36mmHg, which is within +/- 5mmHg of the recorded value
  6. The anion gap is normal: (137) - (92 + 34) = 11, or 13.5 when calculated with potassium

Thus, this patient has a metabolic alkalosis - likely due to vomiting. A diagnostic approach to metabolic alkalosis is offered elsewhere, and goes through this in some detail. In brief, potenial causes include the following:

  • Gastric losses by vomiting or drainage
  • Diuretics:
    • loop diuretics
    • thiazides
  • diarrhoea
  • posthypercapneic state (chronic compensatory renal loss)
  • Primary hyperaldosteronism
  • Mineralocorticoid oversupplementation
  • Licorice (glycyrrhizic acid)
  • β-lactam antibiotics
  • Liddle syndrome
  • Severe hypertension
  • Bartter and Gitelman syndromes
  • Laxative abuse
  • Clay ingestion
  • Recovery from starvation
  • Hypoalbuminemia
  • Hypercalcemia of malignancy
  • Milk-alkali syndrome

References

Khanna, Apurv, and Neil A. Kurtzman. "Metabolic alkalosis." J NEPHROL 2006; 19 (suppl 9): S86-S96

Tripathy, Swagata. "Extreme metabolic alkalosis in intensive care." Indian journal of critical care medicine: peer-reviewed, official publication of Indian Society of Critical Care Medicine 13.4 (2009): 217.

Galla, John H. "Metabolic alkalosis." Journal of the American Society of Nephrology 11.2 (2000): 369-375.

 

Question 9.2 - 2011, Paper 2

A 35-year-old woman with pre-eclampsia is admitted to ICU following an emergency Caesarian section under general anaesthesia for failure to progress during labour at 38 weeks gestation. Arterial blood gas, full blood count and electrolytes post extubation are as follows:

Parameter Patient value    Normal range
 FiO2                                0.5  
  pH                                        7.31*                               7.35 – 7.45        
 PaO2                                        150 mmHg (19.7 kPa)  
 PaCO2                                  42 mmHg (5.5 kPa) 35 – 45 (4.6 – 6.0)     
 HCO3                                      20.1* mmol/l    22 – 27    
Base Excess               -5      -2.0 – +2.0         
Sodium                        137 mmol/l     135 – 145               
 Potassium                        4.3 mmol/l   3.5 – 5.0                
 Haemoglobin                   110* g/l                        125 – 165   
 White cell count          19.8* x 109/l                 4.0 – 11.0                 
 Neutrophils                       17.3* x 109/l                  1.8 – 7.5   
 Lymphocytes                       2.5 x 109/l                    1.5 – 4.0

a) Describe and explain the acid-base status

b) Calculate and interpret the A-a gradient

c) What is the likely significance of the anaemia and the leukocytosis?

College Answer

a)
Acute respiratory acidosis

At 38 weeks pregnancy the normal PaCO2 is <30 mmHg with a compensatory reduction in bicarbonate. The blood gases therefore indicate acute CO2 retention probably due to pain and narcotics. 
In the non-pregnant patient these results would indicate an uncompensated normal anion gap metabolic acidosis.

b)
A-a gradient – this is raised at 154 mmHg, suggesting shunt and/or V/Q mismatch. Possible explanations are the loss of FRC after abdominal surgery, segmental collapse/consolidation or aspiration

c)
Hb and WCC – the mild anaemia is physiological in pregnancy and the neutrophil leukocytosis is a normal feature during labour and early post-partum.

Discussion

This ABG interpretation question is testing the candidate's knowledge of normal changes in the biochemistry of the pregnant woman.

This question closely resembles Question 18 from the first paper of 2006.

Instead of trying to justify why one identical question ended up in the O&G section and the other among the acid-base questions, I will instead focus on the acid-base and gas exchange abnormalities, for a second forgetting that the patient is pregnant. The obstetric flavour is dealt with in the other version of this discussion section.

For b)

There is a mild respiratory acidosis. The normal CO2 of late pregnancy is around 30mmHg, which is generally sustained with a bicarbonate of 20. In this scenario the bicarbonate has not changed, and the CO2 is elevated by 12mmHg.

That makes one think: is the pH influenced by any other disorder? One of the standard equations comes to mind. Every 1mmHg of change in Pa CO2 leads to a 0.008 change in pH. The use of the standard equation yields an expected pH of 7.304 for this 12mmHg change in CO2- very close to the measured pH (7.31)

The anion gap is normal if you calculate it without the potassium. It is 15.3 with potassium included, trivially elevated (by 3.3).

Now, as for the A-a gradient:

A-a gradient = (FiO2 x (760-47) - (PCO2 x 1.25) - PaO2

The humidity is always 100% so the left side of the equation is always FiO2 x 713.

So: (0.5 x 713) - (42 x 1.25)

Thus, the alveolar oxygen concentration is 303 mmHg, and the A-a gradient is 153 (303 - 150)

Given that there is a history of abdominal surgery and pregnancy, the causes of this could be
- Post-operative atelectasis 
- Aspiration 
- pulmonary thromboembolism or amniotic fluid embolism

for c), I note that a 15% drop in Hb is normal in pregnancy.

Normal acid-base changes in pregnancy are discussed elsewhere.

References

For a review of physiological changes of pregnancy, one is directed to any obstetrics textbook. I found Obstetric Evidence Based Guidelines By Vincenzo Berghella to have a nice chapter on it.

 

Oh's Intensive Care manual:

Chapter 64   (pp. 684) General  obstetric  emergencies by Winnie  TP  Wan  and  Tony  Gin

Chapter 65   (pp. 692) Severe  pre-existing  disease  in  pregnancy by Jeremy  P  Campbell  and  Steve  M  Yentis

 

Question 22.2 - 2011, Paper 2

A 63-year-old female presented with high fever and abdominal pain. She has gram- negative bacteraemia and septic shock. The following data are from an arterial blood gas analysis:

Parameter

Patient Value

Normal Range

FiO2

0.3

pH

7.43

7.35 – 7.45

PaCO2

23* mmHg (3.0 kPa)

35 – 45 (4.6 – 6.0)

PaO2

107 mmHg (14 kPa)

HCO3

15* mmHg

22 – 26

Standard base excess

-8.6* mmol/l

-2 – +2

Sodium

147* mmol/l

135 – 145

Potassium

6.7* mmol/l

3.2 – 4.5

Chloride

95* mmol/l

100 – 110

Lactate

23.0* mmol/l

< 2

a)  Describe the abnormalities on the above arterial blood gas profile

b)  List three causes of a raised lactate in sepsis

College Answer


a)  Describe the abnormalities on the above arterial blood gas profile

  • Raised A-a DO2 (78)
  • High anion gap (37) metabolic acidosis with markedly raised lactate
  • Metabolic alkalosis (delta ratio > 3)
  • Respiratory alkalosis (PCO2 lower than expected for HCO3)

b)  List three causes of a raised lactate in sepsis

  • Tissue hypoperfusion and hypoxia
  • Use of adrenaline (increased glycolytic flux)
  • Down regulation of pyruvate dehydrogenase by inflammatory mediators
  • Underlying ischaemic tissue

Discussion

This is a straighforward question about ABG interpretation; it presents the candidate with a triple disorder.

This question is frequently repeated. The chapter on the causes of lactic acidosis in sepsis contains a list of past SAQs which are either identical or very similar.

Yes, the A-a gradient is raised: (0.3 x 713) - 18.4 = 195.5, thus the A-a difference is 195.5-107 = 88.5.

How they got 78 I am not sure.

The anion gap is (147) - (95 + 15) = 37, or 43.7 when calculated with potassium.
The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (37 - 12) / (24 - 15) = 2.77. This suggests there is also a metabolic alkalosis.

The PaCO2 expected for this sort of bicarbonate level is 30.3 (15 x 1.5 + 8) which suggests that there is also a respiratory alkalosis.

As for the causes of raised lactate in sepsis... The question asks for 3 causes. In the past, the examiners have been firm in saying that if you produce more than the [requested number] of answers, you will only be marked on the first [requested number] answers.

In any case one can usually come up with a few reasons a septic patient might have a raised lactate. The topic of pyruvate dehydrogenase being inhibited by inflammatory mediators is explored in this article.

References

D C Gore, F Jahoor, J M Hibbert, and E J DeMaria Lactic acidosis during sepsis is related to increased pyruvate production, not deficits in tissue oxygen availability. Ann Surg. 1996 July; 224(1): 97–102.

Question 22.3 - 2011, Paper 2

A 45-year-old man is admitted unconscious to the Emergency Department. His electrolytes are as follows:

Parameter

Patient Value

Normal Range

Sodium

119* mmol/l

135 – 145

Potassium

5.5* mmol/l

3.2 – 4.5

Chloride

80* mmol/l

100 – 110

Bicarbonate

<5* mmol/l

22 - 27

Urea

10* mmol/l

3.0 – 8.0

Creatinine

105 µmol/l

50 – 100

Glucose

13.0* mmol/l

3.0 – 6.0

Lactate

8.8* mmol/l

<2

Measured osmolality

340* mOsm/kg

275 – 295

Urine ketones

Negative

a)  What are the abnormalities?

b)  Give a possible diagnosis

c)  What further tests would you consider to elucidate the cause of the acid base disturbance?

College Answer


a)  What are the abnormalities?

  • Metabolic acidosis with increased anion gap (34 mmol) Increased osmolar gap (approx 85 mmol)
  • Hyperosmolar hyponatraemia
  • Hyperlactataemia
  • Mild hyperglycaemia

b)  Give a possible diagnosis

  • Toxic alcohol ingestion (eg methanol, ethylene glycol)
  • Alcoholic ketoacidosis
  • Formaldehyde ingestion
  • DKA possible but osmolar gap in this case higher than expected for DKA

c)  What further tests would you consider to elucidate the cause of the acid base disturbance?

  • Specific assays for methanol, ethylene glycol, alcohol
  • Urinary calcium oxalate crystals (ethylene glycol)
  • Formate level (metabolite of methanol)

Discussion

This is a straighforward question about high osmolar gap high anion gap metabolic acidosis.

The anion gap is (119) - (80 + 5) = 34, or 39.5 when calculated with potassium
The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (34 - 12) / (24 - 5) = 1.15, making this a pure HAGMA.

There is also a high osmolar gap of 79 (340- (119x2 + 10+ 13))

Hyperosmolar hyponatremia is not asked about, but is still interesting as an aside.

The causes of a metabolic acidosis with a raised anion gap and a raised osmolar gap are numerous, and well discussed in the literature. Specifically, methanol and the other toxic alcohols are a common cause, and are dealt with in detail elsewhere.

Alcoholic ketoacidosis is mentioned as a differential, although the urinary ketones are absent from the scenario sample. This may be because beta-hydroxybutyrate, the major ketone in alcoholic ketoacidosis, is not detected by urine dipsticks (which look for acetone and acetoacetate).

 

References

Smith SW, Manini AF, Szekely T, Hoffman RS.. Bedside detection of urine beta-hydroxybutyrate in diagnosing metabolic acidosis. Acad Emerg Med. 2008 Aug;15(8):751-6.

Kraut JA, Xing SX. Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis. Am J Kidney Dis. 2011 Sep;58(3):480-4.

Question 8.1 - 2012, Paper 1

a) A 74-year-old man with known ischaemic heart disease was admitted to hospital for treatment of worsening heart failure (day 1). Despite treatment for heart failure he failed to improve and was referred for urgent intensive care assessment on day 5.


Parameter

Measured value

Normal range

Day 1

Day 5

pH

7.52

7.06

7.35-7.45

PaCO2

45 (5.9)

109* (14.3*)

35-45 mmHg (4.6-6.0 kPa)

PaO2

141(18.5)

86.2 (11.3)

80-100 mmHg (10.5-13.0 kPa)

Oxygen Saturation

99.7

89.4

>95%

HCO3

36.5*

29.5*

22-27 mmol/l

Base Excess

12.6*

-0.2

-2 to +2 mmol/L

Hb

94*

112*

130-150 g/L

Sodium

141

132*

135-145 mmol/l

Potassium

4.2

5.2*

3.2-4.5 mmol/l

Chloride

97*

92*

100-110 mmol/l

Glucose

6.0

19.4*

3.0-6.0 mmol/l

Lactate

1.8

6.8*

< 2.0 mmol/l

Creatinine

83

73

50-100 μmol/l

i. Describe the acid-base abnormality on the Day 1 blood gas and give a clinical explanation that most likely caused this picture

ii. Describe the acid-base abnormality on the Day 5 blood gas and give three possible clinical explanations

College Answer

i.

  • Chronic metabolic alkalosis with partial respiratory compensation
  • Background of chronic metabolic alkalosis with partial respiratory compensation could be due to diuretic therapy for heart failure (“contraction alkalosis")

ii.

  • Superimposed acute respiratory acidosis and metabolic acidosis (raised lactate)
  • Concomitant metabolic alkalosis given that the acidosis is not severe for the degree of PCO2 and lactate + BE is normal for the lactate + AG is also normal.
  • The acute superimposed pathology:
    • Cardiogenic shock
    • Sepsis
    • Respiratory depression from opiate or illness
    • PE

Any other reasonable cause

Discussion

This is another one of those "analyse this ABG" questions.

So, lets.

In the first gas, the result that stands out is the high pH, with a relatively normal (or slightly elevated) pCO2 and with a raised bicarbonate. This makes one think of metabolic alkalosis. However, is it properly compensated?

For one the pH is 7.52, and the PCO2 seems too low by gut feel.

The compensation equation for metabolic alkalosis is 0.7 x [HCO3-] + 20; so the PCOin this case should be something like 40-50. (the equation gives us 45mmHg, and it allows +/- 5mmHg error). So, in actual fact the metabolic alkalosis is properly compensated, at least according to the commonly used bedside rules.

So, I suppose we can blame this on frusemide.

Now, for the day 5 gas.

The pH is low; there is acidaemia.

The pCO2 is raised; and it was not raised on day 1, so it is an acute hypercapnea.

If this were a purely respiratory disorder, we would expect the bicarbonate to increase by 1mmol/L for every 10mmHg increase in CO2. There is an increase of 69mmHg of CO2, which should give us a bicarbonate value of 31mmol/L or so.

However, the measured bicarbonate is 29.5, which means a metabolic acidosis is also in play.

The anion gap is (141) - (97 + 36) = 8, or 12.2 when calculated with potassium - essentially normal. 

There is a lactate rise, which contributes to this tiny increase in the anion gap. We know there is also a metabolic alkalosis in the background.

Thus, this is a triple disorder, where a metabolic alkalosis maintained by frusemide has been upset by an acute respiratory acidosis and an acute lactic acidosis.

The college answer does not delve too deeply into this.

They ask us then, what could have caused such a rise in lactate and such hypercapnea in this cardiac patient?

"any reasonable cause" is what they want. One can argue that this old man might have developed cardiogenic shock and his hypercapnea is due to his having lost consciousness from low cardiac output; or might have developed an aspiration pneumonia (SaO2 is 89%). Or sepsis of some unknown origin.

Any reasonable cause.

References

Question 8.2 - 2012, Paper 1

b) A 67-year-old lady is transferred from a regional hospital to a tertiary referral centre with a diagnosis of septic shock from a urinary source. She has not improved despite 48 hours of treatment with antibiotics and supportive care. 
 

Parameter

Measured value

Normal range

Admission

pH

6.93*

7.35-7.45

PaCO2

48* (6.3*)

35-45 mmHg (4.6-6.0 kPa)

PaO2

160 (21.0*)

80-100 mmHg (10.5-13.0 kPa)

Oxygen Saturation

99.2

>95%

HCO3

10*

22-27 mmol/l

Base Excess

-22*

-2 to +2 mmol/L

Sodium

123*

135-145 mmol/l

Potassium

5.4*

3.2-4.5 mmol/l

Chloride

95*

100-110 mmol/l

Glucose

7.0*

3.0-6.0 mmol/l

Lactate

2.8*

< 2.0 mmol/l

Urea

33.0*

3.5-7.2 mmol/l

Creatinine

541*

50-100 ol/l

i. Describe her biochemical profile on admission

ii. List the causes of a raised lactate in sepsis

College Answer

i.

  • Mixed acidosis: Severe metabolic acidosis with a raised anion gap + additional respiratory acidosis
  • Renal failure with hyponatraemia and hyperkalaemia

ii.

  • Adrenaline
  • Pyruvate dehydrogenase inhibtion by endotoxin
  • Liver dysfunction/failure
  • Tissue hypoxia

Discussion

This question is a fairly straightforward ABG interpretation exercise.

  1. The FiO2 is not known, but the patient has a reasonable PaO2 and oxygen saturation.
  2. There is severe acidaemia
  3. The CO2 is contributing.
  4. There is a severe metabolic acidosis. The bicarbonate is 10.
    The anion gap is (123) - (95 + 10) = 18, or 23.4 when calculated with potassium
     
  5. There is no compensation for the metabolic acidosis - the expected CO2 would be 18 (using the SBE) or 23 (using the Boston rules), meaning that there is also a respiratory acidosis.
  6. The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (18 - 12) / (24 - 10) = 0.42. Thus, this is a mixed high and normal anion gap metabolic acidosis, which is exactly the sort of thing you'd see in renal failure. Given that the lactate does not explain the entire magnitude of the anion gap increase, we can speculate that various non-volatile acids are to blame. 

There are many different reasons for why lactate might rise in sepsis. Apart from the shocked state, there is the catecholamine release, microvascular shunting, mitochondrial dysfunction due to pyruvate dehydrogenase inhibition, and diminished hepatic blood flow. I tried to explain this to myself in another chapter.

References

www.anaesthesiamcq, as always.

Jones, Alan E., and Michael A. Puskarich. "Sepsis-induced tissue hypoperfusion." Critical care clinics 25.4 (2009): 769.

Crouser, Elliott D. "Mitochondrial dysfunction in septic shock and multiple organ dysfunction syndrome." Mitochondrion 4.5 (2004): 729-741.

Levy, Bruno. "Lactate and shock state: the metabolic view." Current opinion in critical care 12.4 (2006): 315-321.

Bateman, Ryon M., Michael D. Sharpe, and Christopher G. Ellis. "Bench-to-bedside review: microvascular dysfunction in sepsis-hemodynamics, oxygen transport, and nitric oxide." CRITICAL CARE-LONDON- 7.5 (2003): 359-373.

Question 8.3 - 2012, Paper 1

b) A 75-year-old woman with a reduced level of consciousness is intubated and ventilated following a single grand mal convulsion.

List the pathophysiological disturbances revealed by the following arterial blood gas and electrolyte profile taken 10 mins after intubation and give the likely explanation.

Parameter

Measured value

Normal range

FiO2

1.0

pH

7.05*

7.35-7.45

PaCO2

43 (5.6)

35-45 mmHg (4.6-6.0 kPa)

PaO2

280 (36.8)

80-100 mmHg (10.5-13.0 kPa)

HCO3

11.5*

22-27 mmol/l

Base Excess

-16.8*

-2 to +2 mmol/L

Sodium

128*

135-145 mmol/l

Potassium

3.1*

3.2-4.5 mmol/l

Chloride

82*

100-110 mmol/l

Glucose

79*

3.0-6.0 mmol/l

Lactate

9.2*

< 2.0 mmol/l

Urea

22.0*

3.5-7.2 mmol/l

Creatinine

120*

50-100 μmol/l

College Answer

Uncompensated metabolic acidosis (or metabolic + respiratory acidosis) with raised anion gap not solely due to elevated lactate. 
Raised A-a gradient
Sodium adjusted to normoglycaemia is about 153 
Marked hyperglycaemia (candidates will say this but does not deserve a mark)

Hyperosmolar hyperglycaemic syndrome with component of ketoacidosis and post-ictal lactic acidosis.

Discussion

This ABG interpretation question is testing the candidate's knowledge of the sodium correction equation.

There is a widened A-a gradient, around 270mmHg. The expected PaO2 is around 550mmHg.

There is marked acidaemia; this is due to a metabolic acidosis.

The metabolic acidosis is poorly compensated - the expected CO2 is 24. Thus, there is also a respiratory acidosis.

This is because the patient is ventilated, and has no voluntary compensation mechanisms.

The anion gap is (128) - (82 + 11) = 35, or 38.1 when calculated with potassium. Some, but not all of this is accounted for by the raised lactate.
The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (35 - 12) / (24 - 11) = 1.76
This suggests a pure high anion gap metabolic acidosis. The glucose of 79 would suggest that ketones may be contributing to the high anion gap.

There is also some renal impairment.

There is hypernatremia- when adjusted for glucose, the sodium level is ~ 150 mmol/L.

(for every 5.6mmol/L of glucose, sodium drops by 1.6mmol/L)

Thus this is a hyperosmolar state with respiratory acidosis following intubation, metabolic acidosis likely due to ketones, and lactic acidosis likely due to seizures.

Specific summaries dealing with these topics are available:

References

 

Hyperglycemic Comas by P. VERNON VAN HEERDEN from Vincent, Jean-Louis, et al. Textbook of Critical Care: Expert Consult Premium. Elsevier Health Sciences, 2011.

 

Oh's Intensive Care manual: Chapter 58  (pp. 629) Diabetic  emergencies  by Richard  Keays

 

Umpierrez, Guillermo E., Mary Beth Murphy, and Abbas E. Kitabchi. "Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome." Diabetes Spectrum15.1 (2002): 28-36.

 

ARIEFF, ALLEN I., and HUGH J. CARROLL. "Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of theraphy in 37 cases." Medicine 51.2 (1972): 73-94.

 

Gerich, John E., Malcolm M. Martin, and Lillian Recant. "Clinical and metabolic characteristics of hyperosmolar nonketotic coma." Diabetes 20.4 (1971): 228-238.

 

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes." Diabetes care 32.7 (2009): 1335-1343.

 

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes a consensus statement from the American Diabetes Association." Diabetes care 29.12 (2006): 2739-2748.

 

Question 3.2 - 2012, Paper 2

A 64-year-old man with a background of heavy alcohol consumption has been admitted to your ICU for several days with a sensitive staphylococcus aureus (MSSA) epidural abscess which has been surgically drained.

The following results were obtained.

Parameter

Value

Normal Range

Sodium

143 mmol/L

134 – 146

Potassium

4.0 mmol/L

3.4 – 5.0

Chloride

114 mmol/L*

100 – 110

Urea

10.1 mmol/L*

3.0 – 8.0

Creatinine

104 mmol/L

50 – 120

Glucose

6.9 mmol/L

3.0 – 7.0

Urinary ketones

Negative

Measured osmolality

300 mOsm/Kg

280 – 300

On 30% oxygen arterial blood gas analysis as follows:

Parameter

Value

Normal Range

pH

7.22*

7.35

– 7.45

PO2

84 mmHg (11kPa)

PCO2

25 mmHg (3.2 kPa)*

35

45 (4.6 – 6.0)

Bicarbonate

10 mmol/L*

22

27

Lactate

1.8 mmol/L*

<2.0

What is the likely cause of the acid base disturbance?

How would you investigate and manage it?

 

College Answer

High anion gap metabolic acidosis secondary to pyroglutamic acidaemia.

Can be detected by requesting an organic acid screen, or by plasma or urine pyroglutamate levels.

Management – cessation of precipitating drugs likely paracetamol and flucloxacillin in this case.

N-Acetyl cysteine infusion has been advocated.


Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high:
    PAO2 = (0.3 × 713) - (25 × 1.25) = 182.55
    Thus, A-a = ( 182.55 - 84) = 98.55mmHg.
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is not offered but the bicarbonate is 10, suggesting a severe metabolic acidosis
  5. The respiratory compensation is adequate - the expected PaCO2(10 × 1.5) + 8 = 23mmHg (withn +/- 2mmHg of the reported value)
  6. The anion gap is raised:
     (143) - (114 + 10) = 19, or 23 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (19 - 12) / (24 - 10) = 0.5
    This suggests that there is mixed high anion gap and normal anion gap metabolic acidosis here.
  7. Urinary pH and electrolytes are not offered (but would be interesting)

So, what is making this drunk so acidotic? The lactate is not raised; so the differentials for the high anion gap here would include the following:

  • Methanol and the toxic alcohols in general
  • Ethylene glycol
  • Diabetic, alcoholic and starvation ketoacidosis
  • Pyroglutamic acidosis
  • Salicylate overdose
  • Iron overdose

Of course, the MSSA story suggests the college want us to consider pyroglutamic acidosis as a cause.
Investigations for these differentials would include the following:

  • 5-oxoproline level in urine
  • Urinary oxalate
  • Methanol levels
  • Ketone levels
  • Iron studies
  • Salicylate levels

One would want to stop feeding this man the paracetamol and flucloxacillin.

References

Dempsey GA Lyall HJ, Corke CF, Scheinkestel CD. Pyroglutamic acidemia: a cause of high anion gap metabolic acidosis. Crit Care Med. 2000Jun;28(6):1803-7.

Duewall, Jennifer L., et al. "5-Oxoproline (pyroglutamic) acidosis associated with chronic acetaminophen use." Proceedings (Baylor University. Medical Center) 23.1 (2010): 19.

Akhilesh Kumar and Anand K. Bachhawat Pyroglutamic acid: throwing light on a lightly studied metabolite ,SPECIAL SECTION: CHEMISTRY AND BIOLOGY. CURRENT SCIENCE, VOL. 102, NO. 2, 25 JANUARY 2012. 288

 

Question 6.1 - 2012, Paper 2

The following blood gases, electrolytes and full blood count relate to a 32-year-old woman post-extubation, following an emergency lower segment Caesarian section at 38 weeks gestation for foetal distress during labour:

Parameter

Result

Normal Values

Barometric pressure

760 mmHg

FiO2

0.5

pH

7.31*

7.35 – 7.45

PO2

150 mmHg (19.7 kPa)

PCO2

42 mmHg (5.5 kPa)

35 – 45 (4.6 – 6.0)

HCO3

20.3 mmol/L*

22 – 27

Standard BXS

-5.0 mmol/L*

-2 – +2

Sodium

137 mmol/L

135 – 145

Potassium

4.3 mmol/L

3.2 – 4.5

Chloride

106 mmol/L

100 – 110

Haemoglobin

110 G/L*

125 – 165

White cell count

19.8 x 109/L*

4.0 – 11.0

Neutrophils

17.3 x 109/L*

1.8 – 7.5

Lymphocytes

1.8 x 109/L

1.5 – 4.0

  • Comment on and interpret the arterial blood gases and the acid-base status.
  • What is the significance of the haemoglobin concentration and white cell count?
 

College Answer

a)

Raised A-a gradient of 154 mmHg suggestion shunt and/or V/Q mismatch. Potential explanations are loss of FRC post abdominal surgery, segmental collapse/consolidation or aspiration.

Acute respiratory acidosis – normal PCO2 for 38 weeks gestation is 30 mmHg with compensatory reduction in HCO3. CO2 retention is possibly due to pain, narcotics and/or sedation from anaesthetic agents

Normal anion gap

b)

Anaemia and leukocytosis – mild anaemia is physiological in pregnancy. Neutrophil leukocytosis is a normal feature during labour and early post-partum.

Discussion

This question is very similar to Question 6.2 from the first paper of 2013.

Let us dissect these results systematically.

  1. The A-a gradient is high; 
    PAO2 = (0.5 × 713) - (42 × 1.25) = 304
    Thus, A-a = (304-150) = 154mmHg.
  2. There is acidaemia
  3. The PaCO2 is contributing to the acidosis
  4. The SBE is -5, suggesting a metabolic acidosis
  5. The respiratory compensation is inadequate - the expected PaCO2(20.3 × 1.5) + 8 = 38.45mmHg, and thus there is also a mild respiratory acidosis (especially considering that in pregnancy the normal CO2 value is around 30mmHg)
  6. The anion gap is normal:
    (137) - (106 + 20) = 11, or 15.3 when calculated with potassium

Thus, the main disorder here is respiratory acidosis (as the metabolic contribution is minimal - the bicarbonate is close to its normal value in pregancy).

The leukocytosis and anaemia are quite normal peripurpureal findings.

References

Oh's Intensive Care manual:

Chapter 64   (pp. 684) General  obstetric  emergencies by Winnie  TP  Wan  and  Tony  Gin

Chapter 65   (pp. 692) Severe  pre-existing  disease  in  pregnancy by Jeremy  P  Campbell  and  Steve  M  Yentis

Hegewald, Matthew J., and Robert O. Crapo. "Respiratory physiology in pregnancy." Clinics in chest medicine 32.1 (2011): 1-13.

Milne, J. A. "The respiratory response to pregnancy." Postgraduate medical journal 55.643 (1979): 318-324.

 

Question 21.2 - 2012, Paper 2

A 52-year-old man with a history of alcohol abuse and Type 2 diabetes is admitted with the abdominal pain. His arterial blood gases and biochemical profile are as follows:

Parameter

Result

Normal Range

Barometric pressure

760 mmHg (100 kPa)

FiO2

0.5

pH

7.14*

7.35 – 7.45

PCO2

12 mmHg (1.1 kPa)*

35 – 45 (4.7 – 6.0)

PO2

149 mmHg (20 kPa)

Bicarbonate

4 mmol/L*

22 – 26

Lactate

16 mmol/L*

<2.0

Sodium

142 mmol/L

135 – 145

Potassium

4.7 mmol/L*

3.2 – 4.5

Urea

14 mmol/L*

3.0 – 8.0

Creatinine

0.17 mmol/L*

0.07 – 0.12

Glucose

6.5 mmol/L

3.6 – 7.7

Total Bilirubin

20 micromol/L

4 – 25

LDH

1400 U/L*

50 – 150

AST

60 U/L*

<40

ALT

70 U/L*

<40

Serum Osmolality

314 mOsm/Kg*

275 – 295

  1. Give three likely underlying diagnoses
  2. Give two additional investigations that would assist the diagnosis

College Answer

a)

  • Ischaemic bowel
  • Metformin induced lactic acidosis
  • Septic shock
  • Thiamine deficiency
  • Pancreatitis

b) 

  • CT abdomen
  • Blood cultures / septic screen
  • Lipase
  • Red cell transketolase 
    Diagnostic laparoscopy / laparotomy

Discussion

This question is identical to Question 15.3 from the second paper of 2009, and Question 26.4 from the second paper of 2013. The answer to the latter contains a comprehensive discussion.

References

Question 21.3 - 2012, Paper 2

A 79-year-old woman with a history of Type 2 diabetes presents with confusion and a decreased conscious state. The following are her blood results on admission:

Parameter

Result

Normal Range

Barometric pressure

760 mmHg (100 kPa)

FiO2

0.4

pH

7.32

7.35 – 7.45

PCO2

36 mmHg (4.0 kPa)

35 – 45 (4.7 – 6.0)

PO2

90 mmHg (12.0 kPa)

Bicarbonate

18 mmol/L*

22 – 26

Lactate

4.8 mmol/L*

<2.0

Sodium

140 mmol/L

135 – 145

Potassium

3.9 mmol/L

3.2 – 4.5

Chloride

105 mmol/L

100 – 110

Urea

21.8 mmol/L*

3.0 – 8.0

Creatinine

0.22 mmol/L*

0.07 – 0.12

Glucose

40 mmol/L*

3.6 – 7.7

  • What is the most likely condition consistent with these results? Give the rationale for your answer.
  • List four potential complications of this condition.

College Answer

a) 

  • Non-ketotic hyperosmolar state:
  • Marked hyperglycaemia – higher than usually seen in DKA
  • Hyperosmolar – approx. 342 mOsm/Kg
  • Relatively mild anion gap acidosis accounted for by raised lactate

b)

  • Cerebral oedema
  • Vascular thrombosis
  • Electrolyte derangement
  • Intercurrent events such as sepsis, AMI Hypotension and shock if inadequate resuscitation
  • Death


 

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high; 194 or 337.6mmHg depending on what FiO2 you think the Hudson mask is delivering.
    PAO2 = (0.4 × 713) - (36 × 1.25) = 240.2
    Thus, A-a = ( 240.2 - 90) = 150.2mmHg.
  2. There is acidaemia
  3. The PaCO2 is vaguely compensatory
  4. The SBE is not offered but the bicarbonate is 18, suggesting a metabolic acidosis
  5. The respiratory compensation is adequate - the expected PaCO2(18 × 1.5) + 8 = 35mmHg
  6. The anion gap is raised:
    (140) - (105 + 18) = 17, or 20.9 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (17 - 12) / (24 - 18) = 0.83
    This suggests that there is a mixed high anion gap and normal anion gap metabolic acidosis here.
     

The glucose of 40, urea creatinine and the raised lactate are all giveaway clues.

Ths patient has HONK and uremic renal failure. The calculated osmolarity is (140 × 2 + 21.8 + 40) = 341.8 mOsm/L.

Complications of HONK, as listed in the abovelinked page, are as follows:

  • Cardiac arrest
  • Cardiovascular collapse
  • Myocardial infarction
  • Stroke
  • Cerebral oedema and brain injury
  • Venous thrombosis

I do not see how listing "death" as a complication earns any marks in this exam.

References

Hyperglycemic Comas by P. VERNON VAN HEERDEN from Vincent, Jean-Louis, et al. Textbook of Critical Care: Expert Consult Premium. Elsevier Health Sciences, 2011.

Oh's Intensive Care manual: Chapter 58  (pp. 629) Diabetic  emergencies  by Richard  Keays

Umpierrez, Guillermo E., Mary Beth Murphy, and Abbas E. Kitabchi. "Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome." Diabetes Spectrum15.1 (2002): 28-36.

ARIEFF, ALLEN I., and HUGH J. CARROLL. "Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of theraphy in 37 cases." Medicine 51.2 (1972): 73-94.

Gerich, John E., Malcolm M. Martin, and Lillian Recant. "Clinical and metabolic characteristics of hyperosmolar nonketotic coma." Diabetes 20.4 (1971): 228-238.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes." Diabetes care 32.7 (2009): 1335-1343.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes a consensus statement from the American Diabetes Association." Diabetes care 29.12 (2006): 2739-2748.

Ellis, E. N. "Concepts of fluid therapy in diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma." Pediatric clinics of North America 37.2 (1990): 313-321.

Pinies, J. A., et al. "Course and prognosis of 132 patients with diabetic non ketotic hyperosmolar state." Diabete & metabolisme 20.1 (1993): 43-48.

Question 28 - 2012, Paper 2

A 76-year-old man is admitted to ICU following a Medical Emergency Team call for hypotension and tachypnea. He is three days post-laparoscopic anterior resection for sigmoid cancer.

Information from his arterial blood gas is as follows:

Parameter

Result

Normal Range

Sodium

138 mmol/L

135 – 145

Potassium

5.4 mmol/L*

3.5 – 4.5

Chloride

104 mmol/L

95 – 105

Barometric pressure

760 mmHg (100 kPa)

FiO2

0.4

pH

7.01*

7.35 – 7.45

PCO2

45 mmHg (6 kPa)

35 – 45 (4.6 – 6)

PO2

84 mmHg (11 kPa)

Bicarbonate

11 mmol/L*

22 – 27

Base Excess

-19 mmol/L*

-2.0 – +2.0

Haemoglobin

88 G/L*

135 - 180

Glucose

7.5 mmol/L*

3.5 – 7.0

Lactate

13 mmol/L*

<2.0

  • Comment on the above results
  • What are the likely underlying causes of the raised lactate?
  • What are your immediate management priorities for this man?

College Answer

a)

High anion gap metabolic acidosis

AG 23 not accounted for by just rise in lactate

Marked lactic acidosis

Respiratory acidosis

Hypoxaemia with A-a DO2 145

Anaemia

b)

Septic shock (intra-abdo, lung, other)

Hypovolaemic shock with intra-abdominal bleeding

Ischaemic gut

Cardiogenic shock (myocardial ischaemia or septic ardiomyopathy)

PE less likely with PO2 84 on FiO2 0.4 but cannot be excluded

c)

Resuscitation with simultaneous focussed assessment (history, examination, investigations) to ascertain diagnosis and institution of treatment (supportive and definitive)

Resuscitation – ensure adequate airway and ongoing adequate oxygenation and ventilation. Intubation and IPPV if needed. IV access and fluid resus plus/minus vasopressors.

Focussed assessment – differential diagnosis as above. Look for signs of bleeding, sepsis, intra-abdominal catastrophe, assess myocardial function

Investigations – FBC, U&E, coags, Troponin, septic screen, ECG, CXR, CT abdo (if stable) ± CTPA, bedside echo

Broad-spectrum antibiotics if sepsis suspected

Surgical review, consider proctoscopy, with urgent return to theatre if indicated (anastamotic leak, ischaemic gut)

Other urgent specific treatment as indicated eg stop bleeding, treat myocardial ischaemia Monitoring and transfer to ICU/HDU

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high:
    PAO2 = (0.4 × 713) - (45 × 1.25) = 157.55
    Thus, A-a = ( 157.55 - 84) = 73.55mmHg.
  2. There is acidaemia
  3. The PaCO2 is contributing to the acidosis
  4. The SBE is -19, suggesting a severe metabolic acidosis
  5. The respiratory compensation is inadequate - the expected PaCO2(11 × 1.5) + 8 = 24.5mmHg, and thus there is also a respiratory acidosis.
  6. The anion gap is raised:
    (138) - (104 + 11) = 23, or 28.4 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (23 - 12) / (24 - 11) = 0.84
    The delta ratio suggests that there is a mixed high anion gap and normal anion gap metabolic acidosis here.
     

The lactate is 13, which can account for most -but not all- of the increase in the anion gap.

So: why is it so high, the college asks?

Differentials relevant to this case might include the following:

  • Ischaemic gut
  • Sepsis with intra-abdominal collection
  • Cardiogenic shock
  • Haemorrhagic shock
  • "Obstructive" shock - PE or cardiac tamponade

Approaching the management systematically, one might respond to the last question in the following fashion:

  • Attention to the ABCS, with management of life-threatening problems simultanous with a rapid focused examination and a brief history
  • Airway
    • Assess the need to control the airway
    • This patient will probably require intubation
  • Breathing/ventilation
    • Aim for a lower PaCO2 to help correct the acidosis
    • Apply PEEP to improve oxygenation
    • A CXR would be helpful
  • Circulatory support
    • Fluid resuscitation should commence
    • Vasopressors will likely be required
    • Central venous access needs to be established
    • Invasive hemodynamic monitoring will be required
    • a TTE would be helpful
  • Specific investigations
    • A CT of the abdomen is required
    • A septic screen should be sent
  • Specific management
    • A surgical opinion is required
    • Broad-spectrum antibiotics cannot be delayed

References

Oh's Intensive Care manual: Chapter   45   (pp. 520) Abdominal  surgical  catastrophes by Stephen  J  Streat

Marshall, John C., and Marilyn Innes. "Intensive care unit management of intra-abdominal infection." Critical care medicine 31.8 (2003): 2228-2237.

Gajic, Ognjen, et al. "Acute abdomen in the medical intensive care unit."Critical care medicine 30.6 (2002): 1187-1190.

Question 3.4 - 2013, Paper 1

For each set of the following biochemical and arterial blood gas parameters:

  • Describe the abnormalities.
  • Give one example of an associated clinical scenario.

Any reasonable scenario accepted that was both biochemically correct AND clinically likely.

Test

Value

Normal Adult Range

Sodium

145 mmol/L

135 – 145

Potassium

4.0 mmol/L

3.2 – 4.5

Chloride

101 mmol/L

100 – 110

Bicarbonate*

34 mmol/L

24 – 32

pH*

7.2

7.35 – 7.45

pCO2*

90 mmHg (11.7 kPa)

35 – 45 (4.6 – 5.9)

College Answer

Acute respiratory acidosis with metabolic alkalosis.

Clinical scenario – acute respiratory failure in COAD (Acute on chronic respiratory failure.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated - the information is missing
  2. There is acidaemia
  3. The PaCO2 is massively elevated, suggesting a primary respiratory acidosis
  4. The SBE is not supplied, but the bicarbonate is 34, suggestive of a metabolic alkalosis
  5. The metabolic compensation may not have titrated the pH back to normality, but it appears to be excessive - the HCO3is expected to increase by 1mmol/L for every 10mmHg increase in CO2 in an acute respiratory acidosis, which would give us (10 × 5 + 24) = 29mmol/L. The fact that the HCO3- is 34mmol/L suggests that there is a metabolic alkalosis present.
  6. The anion gap is essentially normal: 
    (145) - (101 + 34) = 10, or 14 when calculated with potassium
  7. The delta ratio is of no use here.
  8. The urinary electrolytes and pH would not be helpful.

Thus, this is a respiratory acidosis with a coexisting  metabolic alkalosis. Anion gap is normal. Scenarios which might explain these findings may be any of the following:

  • Hypercapneic respiratory failure in chronic COPD
  • Respiratory failure due to acute pulmonary oedema in a patient on chronic loop diuretic therapy
  • Hypercapneic respiratory failure due to obtundation in a vomiting opium fiend

References

Bear, R., et al. "Effect of metabolic alkalosis on respiratory function in patients with chronic obstructive lung disease." Canadian Medical Association Journal117.8 (1977): 900.

Bruno, Cosimo Marcello, and Maria Valenti. "Acid-base disorders in patients with chronic obstructive pulmonary disease: a pathophysiological review."BioMed Research International 2012 (2012).

Question 3.5 - 2013, Paper 1

For each set of the following biochemical and arterial blood gas parameters:

  • Describe the abnormalities.
  • Give one example of an associated clinical scenario.

Any reasonable scenario accepted that was both biochemically correct AND clinically likely.

Test

Value

Normal Range

Sodium

135 mmol/L

135 – 145

Potassium

4.0 mmol/L

3.2 – 4.5

Chloride

105 mmol/L

100 – 110

Bicarbonate*

22 mmol/L

24 – 32

pH*

7.60

7.35 – 7.45

pCO2*

23 mmHg (3.0 kPa)

35 – 45 (4.6 – 5.9)

 

College Answer

Acute respiratory alkalosis. Clinical scenario – Psychogenic hyperventilation

Discussion

Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated - the information is missing
  2. There is alkalaemia
  3. The PaCO2 is decreased, suggesting that it is contributing to the alkalosis
  4. The SBE is not supplied, but the bicarbonate is 22, suggestive of a metabolic acidosis or metabolic compensation
  5. The metabolic compensation may not have titrated the pH back to normality, but it appears to be adequate - the HCO3is expected to fall by 2mmol/L for every 10mmHg of acute decrease in CO2 in an acute respiratory alkalosis, which would give us 20mmol/L. The fact that the HCO3- is 22mmol/L suggests that there is a mild metabolic alkalosis present.
  6. The anion gap is normal:
    (135) - (105 + 22) = 8, or 12 when calculated with potassium
    The delta ratio is of no use here.
  7. The urinary electrolytes and pH would not be helpful.

Thus, this is a respiratory alkalosis with virtually no other biochemical changes. A scenario which might explain these findings may be any cause of hyperventilation:

  • Anxiety
  • Fear
  • Pain
  • Dysregulation of central respiratory control (eg. severe brain injury)
  • Ridiculous ventilator settings

References

Barker, E. S., et al. "The renal response in man to acute experimental respiratory alkalosis and acidosis." Journal of Clinical Investigation 36.4 (1957): 515.

Foster, Guy T., Nostratola D. Vaziri, and C. S. Sassoon. "Respiratory alkalosis." Respiratory care 46.4 (2001): 384-391.

Giebisch, Gerhard, et al. "The extrarenal response to acute acid-base disturbances of respiratory origin." Journal of Clinical Investigation 34.2 (1955): 231.

Question 6.1 - 2013, Paper 1

The following arterial blood gas was taken from a female hospitalised for recurrent urinary tract infections. She was transferred to the ICU because of nosocomial pneumonia.

Test

Value

Normal Adult Range

Barometric Pressure

760 mmHg (100kPa)

FiO2

0.3

pH*

7.53

7.35 – 7.45

pCO2*

31 mmHg (4 kPa)

35– 45 (4.6 – 5.9)

pO2*

83 mmHg (11 kPa)

Bicarbonate

25 mmol/L

24– 32

Standard Base Excess*

3.3 mmol/L

-2.0 – +2.0

  • Comment on the acid-base status.
  • List two likely causes of the acid-base abnormality in this patient.

College Answer

6.1 a)

Mixed respiratory and metabolic alkalosis

6.1 b)

Respiratory alkalosis from the hyperventilation due to the pneumonia.

Metabolic alkalosis from vomiting or diuretic use.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high: 
    PAO2 = (0.3 × 713) - (31 × 1.25) = 175
    Thus, A-a = ( 175 - 83) = 92mmHg.
  2. There is alkalaemia
  3. The PaCO2 is contributing to the alkalosis
  4. The SBE is 3.3, suggesting a mild metabolic alkalosis
  5. There is no respiratory compensation.This disorder ends up a mixed metabolic and respiratory alkalosis whichever way you calculate it.
    The expected PaCO2 is (0.7 × 25) + 20 = 37.5mmHg, and thus there is also a respiratory alkalosis. 
    If you were to assume that the respiratory disorder is acute and the primary cause of the problem, you would calculate a 2mmol/L decrease in HCO3- for every 10mmHg drop in PaCO2. That would suggest that the expected HCO3- for this patient would be somewhere in the vicinity of 22mmol/L.

When offering a "likely diagnosis" to explain this gas, one can resort to mix-and-matching any cause of metabolic alkalosis (eg.vomiting, diuretic use) with any cause of respiratory alkalosis (eg. anxiety, pain, etc). For all we know, she maybe prone to panic attacks and has been binge-eating licorice.

References

McCurdy, Donna Kern. "Mixed metabolic and respiratory acid-base disturbances: diagnosis and treatment." CHEST Journal 62.2_Supplement (1972): 35S-44S.

Khanna, Apurv, and Neil A. Kurtzman. "Metabolic alkalosis." J NEPHROL 2006; 19 (suppl 9): S86-S96

Barker, E. S., et al. "The renal response in man to acute experimental respiratory alkalosis and acidosis." Journal of Clinical Investigation 36.4 (1957): 515.

Question 6.2 - 2013, Paper 1

A 29-year-old female is admitted to ICU extubated following an emergency Caesarian section at 38 weeks gestation for pre-eclampsia and failure to progress. The following data were taken on admission to ICU: 
 

Test

Value

Normal Adult Range

Barometric Pressure

760 mmHg (100 kPa)

FiO2

0.4

pH*

7.31

7.35 – 7.45

pCO2

42 mmHg (5.6 kPa)

35– 45 (4.6 – 5.9)

pO2

110 mmHg (14.5 kPa)

Bicarbonate*

20.5 mmol/L

24– 32

Standard Base Excess*

-4.9 mmol/L

-2.0 – +2.0

Comment on this arterial blood gas report and explain the abnormalities.

College Answer

  1. a)

Increased A-a DO2 secondary to decreased FRC post surgery or possible collapse/consolidation or aspiration or pulmonary oedema.

Acute respiratory acidosis on background compensated respiratory alkalosis of pregnancy. CO2 retention secondary to e.g. hypoventilation post anaesthetic.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high:
    PAO2 = (0.4 × 713) - (42 × 1.25) = 232.7
    Thus, A-a = ( 232.7 - 110) = 122.7mmHg.
  2. There is acidaemia
  3. The PaCO2 is contributing to the acidosis(if one recalls that in pregnancy, the PaCO2 is usually somewhat lower than normal)
  4. The SBE is -4.9, suggesting a metabolic acidosis
  5. The respiratory compensation is inadequate - the expected PaCO2(20.5 × 1.5) + 8 = 38.75mmHg, and thus there is also a mild respiratory acidosis. 
    One can also view this in terms of metabolic compensation. The chronic respiratory alkalosis of pregnancy drives the PaCO2 down to about 32-30mmHg, and thus the bicarbonate decreases by 5mmol/L to 19-20mmol/L. Knowing this normal range, one can surmise that in this patient the bicarbonate is actually within the normal range.
  6. The anion gap and delta gap cannot be calculated

Thus: this post-LSCS patient is hypoxic and acidotic, with a predominantly respiratory acidosis. This is not a completely unexpected picture. If she had a spinal, one would be tempted to check her sensory level, to ensure that the respiratory muscles are unaffected. However, the college tells us there was a general anaesthetic. Atelectasis, loss of FRC and opiates are to blame.

References

Loverro, G., et al. "Indications and outcome for intensive care unit admission during puerperium." Archives of gynecology and obstetrics 265.4 (2001): 195-198.

Question 6.3 - 2013, Paper 1

Following laparotomy for haemoperitoneum, a patient is transferred to ICU. Blood biochemistry and arterial blood gas analysis on admission to ICU are as follows:

Test

Value

Normal Adult Range

Sodium*

147 mmol/L

135 – 145

Potassium

3.6 mmol/L

3.2 – 4.5

Chloride*

124 mmol/L

100 – 110

Haemoglobin*

106 G/L

115 – 155

pH*

7.32

7.35 – 7.45

pCO2*

32 mmHg (4.3 kPa)

35 – 45 (4.6 – 5.9)

pO2*

63 mmHg (8.4 kPa)

Bicarbonate*

16.0 mmol/L

24 – 32

Standard Base Excess*

-9.0 mmol/L

-2.0 – +2.0

  • Describe the acid-base status.
  • What is the likely cause of this disturbance?
  • What is the underlying biochemical mechanism?

College Answer

a)

Normal anion gap metabolic acidosis with appropriate respiratory compensation.

b)

Resuscitation with large volume saline infusion.

c)

ECF dilution by fluid with strong ion difference of zero.


Discussion

Let us dissect these results systematically.

  1. The A-a gradient is probably high; the FiO2 is not supplied, but the patient is hypoxic.
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is -9, suggesting a metabolic acidosis
  5. The respiratory compensation is adequate - the expected PaCO2 is (16 × 1.5) + 8 = 32mmHg.
  6. The anion gap is normal:
     (147) - (124 + 16) = 7, or 10.6 when calculated with potassium
  7. Urinary pH and electrolytes would be interesting, but are not supplied.

Thus, this is a normal anion gap metabolic acidosis, which is well compensated. One possible reason for this might be an enthusiastic overabundance of saline.

Judging from the answer, the college was expecting a  Stewart-based physicochemical approach to acid-base analysis, which is rather refreshing to see. Normal saline intoxication is dealt with elsewhere.

References

Story DA. Hyperchloraemic acidosis: another misnomer? Crit Care Resusc. 2004 Sep;6(3):188-92.

Skellett, S., et al. "Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline fluid resuscitation." Archives of Disease in Childhood 83.6 (2000): 514-516.

Constable, Peter D. "Hyperchloremic acidosis: the classic example of strong ion acidosis." Anesthesia & Analgesia 96.4 (2003): 919-922.

Reid, Fiona, et al. "Hartmann’s solution: a randomized double-blind crossover study." Clinical Science 104 (2003): 17-24.

Question 6.4 - 2013, Paper 1

A 33 year old female has Gram-negative bacteraemia and septic shock. The following are data from blood gas analysis.

Test

Value

Normal Adult Range

Barometric pressure

760 mmHg (100 kPa)

FiO2

0.3

pH

7.43

7.35 – 7.45

pCO2*

23 mmHg (3.1 kPa)

35 – 45 (4.6 – 5.9)

pO2

107 mmHg (14.3 kPa)

Bicarbonate*

15 mmol/L

24 – 32

Standard Base Excess*

-8.6 mmol/L

-2.0 – +2.0

Lactate*

23.0 mmol/L

0.2 – 2.5

Sodium*

147 mmol/L

137 – 145

Potassium*

6.7 mmol/L

3.2 – 4.5

Chloride*

95 mmol/L

100 – 110

  • Describe the acid-base abnormalities.
  • What are the possible mechanisms for a raised lactate in sepsis?

College Answer

6.4 a)

Lactic acidosis with anion gap elevation (37 mEq/L).

Metabolic alkalosis (Delta ratio >2).

Respiratory alkalosis (PCO2 lower than predicted for HCO3).

6.4 b)

Tissue hypoperfusion and hypoxia

Use of adrenaline (increased glycolytic flux)

Down regulation of pyruvate dehydrogenase by inflammatory mediators Underlying ischaemic tissue

Discussion

This question is frequently repeated. A detailed discussion is carried out in the discussion of the answer for one such duplicate, Question 6.4 from the first paper of 2013. Otherwise, the causes of lactic acidosis in sepsis are discussed elsewhere.

Let us dissect these results systematically.

  1. The A-a gradient is high:
    PAO2 = (0.3 × 713) - (23 × 1.25) = 185
    Thus, A-a = ( 185 - 107) = 78mmHg.
    However, the college was only interested in the acid-base abnormalities
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is -8.6, suggesting a severe metabolic acidosis
  5. The respiratory compensation is somewhat excessive- the expected PaCO2(15 × 1.5) + 8 = 30.5mmHg, and thus there is also a respiratory alkalosis
  6. The anion gap is raised:
    (147) - (95  + 15) = 37, or 43.7 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (37 - 12) / (24 - 15) = 2.77
    This suggests that the high anion gap metabolic acidosis here is concurrent with a metabolic alkalosis
     

Thus, there is a triple disorder here:

  • Respiratory alkalosis
  • Metabolic alkalosis
  • Metabolic (high anion gap) acidosis

As for the question about sepsis: this is summarised  in the chapter on the causes of lactic acidosis in sepsis. Suffice to say, there are several contributing factors:

  • Shock state: inadequate tissue oxygenation, due to:
    • vasoplegia and low blood pressure
    • sepsis-associated cardiac dysfunction and decreased cardiac output
  • microvascular shunting
  • catecholamine excess influencing an increase in glycolysis
  • mitochondrial dysfunction (pyruvate dehydrogenase inhibition) due to endotoxins and cytokines

flowchart of lactic acidosis in sepsis

Microvascular stasis

Firstly, the slow circulation is to blame; this results in a delay in the delivery of oxygen to the tissues, as well as a delay in removing the metabolic byproducts, which has the tendency to concentrate the lactate. The evidence for this is strong; the term used to describe this is “microvascular stasis” where collecting post-capillary venules are so vasodilated that flow in them essentially halts. There is at least one excellent article which goes over the potential causes for this stasis, including the increased adhesion of blood cells to endothelia, decreased red cell deformability, microthrombi interfering with the flow, etc. etc.

Microvascular shunting

Another feature of sepsis is that in some tissues the circulatory beds are completely shut down, and there is microcirculatory shunting of oxygenated blood away from these tissues. The net result is decreased oxygen extraction from otherwise well oxygenated blood. This is the patient who has a raised lactate in spite of having a normal (or even elevated) ScVO2.

Catecholamine-related increase in glycolysis

Then, there is a catecholamine-driven increase in the rate of glycolysis, predominantly in the skeletal muscles, which leads to an excess of pyruvate. This is seen also in people receiving infusions of salbutamol or adrenaline – the mechanism is the same. Conversely, beta-blockade reverses this effect  and causes lactate to decrease.

Pyruvate dehydrogenase inhibition by cytokines and endotoxin

There is also a significant impairment of mitochondrial function, as a result of direct cytokine effects as well as bacterial endotoxin. The main dysfunction seems more to do with the disruption of mitochondrial enzyme complexes responsible for pyruvate metabolism, particularly pyruvate dehydrogenase.  The outcome of this is a switch to increased anaerobic metabolism, rather than pyruvate oxidation; and of course the amount of available pyruvate also increases.

References

Jones, Alan E., and Michael A. Puskarich. "Sepsis-induced tissue hypoperfusion." Critical care clinics 25.4 (2009): 769.

Crouser, Elliott D. "Mitochondrial dysfunction in septic shock and multiple organ dysfunction syndrome." Mitochondrion 4.5 (2004): 729-741.

Levy, Bruno. "Lactate and shock state: the metabolic view." Current opinion in critical care 12.4 (2006): 315-321.

Bateman, Ryon M., Michael D. Sharpe, and Christopher G. Ellis. "Bench-to-bedside review: microvascular dysfunction in sepsis-hemodynamics, oxygen transport, and nitric oxide." CRITICAL CARE-LONDON- 7.5 (2003): 359-373.

Jansen TC, van Bommel J, Schoonderbeek J, et al: Early lactate-guided therapy in ICU patients:
A multicenter, open-label, randomized, controlled trial
. Am J Respir Crit Care Med 2010 May 12

Nguyen HB, Rivers EP, Knoblich BP, et al. Early lactate clearance is associated with improved outcome

in severe sepsis and septic shock. Crit Care Med 2004;32:1637-42.

Luchette, Fred A., et al. "Adrenergic antagonists reduce lactic acidosis in response to hemorrhagic shock." The Journal of Trauma and Acute Care Surgery 46.5 (1999): 873-880.

Ince, Can, and Michiel Sinaasappel. "Microcirculatory oxygenation and shunting in sepsis and shock." Critical care medicine 27.7 (1999): 1369-1377.

Question 20.2 - 2013, Paper 1

A 23-year-old female was found unconscious at home and subsequently admitted to the ICU. At admission she had the following results:

Test

Value

Normal Adult Range

Sodium*

122 mmol/L

135 – 145

Potassium

3.8 mmol/L

3.2 – 4.5

Chloride*

91 mmol/L

100 – 110

Bicarbonate*

14 mmol/L

24 – 32

Glucose

4.0 mmol/L

3.0 – 6.0

Urea

6.8 mmol/L

2.7 – 8.0

Creatinine*

122 μmol/L

65 – 115

Measured Osmolality*

295 mosmol/Kg

275 – 290

Give the likely diagnosis and the rationale for your answer.

College Answer

Methanol (or some other alcohol) toxicity.

High anion gap acidosis, increased osmolar gap.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated.
  2. There is no pH supplied
  3. The PaCO2 is not given.
  4. The SBE is not available, but the bicarbonate is 14mmol/L, suggesting a metabolic acidosis.
  5. The respiratory compensation cannot be assessed.
  6. The anion gap is raised:
    (122) - (91  + 14) = 17, or 20.8 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (17 - 12) / (24 - 14) = 0.5
    This suggests that there is a mixed high anion gap and normal anion gap metabolic acidosis here.
     
  7. The osmolar gap is increased: 295 - (2 × 122 + 6.8 + 4.0) = 40.2

This young lady is suffering from a high anion gap metabolic acidosis with a high osmolar gap. Clearly, she swilled some sort of osmoles at home, of which only some are responsible for the acidosis. What sort of poisoning is this? Salicylate toxicity and ketoacidosis do not tend to cause such a high osmolar gap, nor does lactic acidosis (until you are nearly dead). Toxic alcohols are the answer implied by the young age of the victim, which suggests a certain sort of ageist cynicism among the examiners.

References

Kraut, Jeffrey A., and Ira Kurtz. "Toxic alcohol ingestions: clinical features, diagnosis, and management." Clinical Journal of the American Society of Nephrology 3.1 (2008): 208-225.

Question 20.3 - 2013, Paper 1

A 35-year-old male has presented to the Emergency Department with weakness and constipation. Whilst in the Emergency Department he had the following results:

Test

Value

Normal Adult Range

Sodium

138 mmol/L

135 – 145

Potassium*

2.6 mmol/L

3.2 – 4.5

Chloride*

119 mmol/L

100 – 110

Bicarbonate*

10 mmol/L

24 – 32

Glucose

5.5 mmol/L

3.0-6.0

Urea

6.4 mmol/L

2.7 – 8.0

Creatinine

98 μmol/L

65-115

Urine Sodium

35

Urine Potassium

50

Urine Chloride

45

Give the likely cause of this disturbance and the rationale for your answer. 

College Answer

Distal (Type 1) RTA 
Hyperchloraemic, normal AG acidosis and severe hypoK, with normal renal function and positive urinary anion gap.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated, for lack of relevant bits.
  2. There is no pH recorded
  3. There is no PaCO2 recorded
  4. The SBE is not offered, but the bicarbonate is very low, suggesting a metabolic acidosis
  5. The respiratory compensation cannot be assessed
  6. The anion gap is normal:
    (138) - (119 + 10) = 9, or 11.6 when calculated with potassium
  7. Urinary pH is not supplied, but the urinary anion gap can be calculated: (35+50) - 45 = 40
    The high urinary anion gap (ie. evidence that chloride excretion is sub-optimal) suggests that a renal tubular acidosis is at play.

Given the extremely low bicarbonate value, and the hypokalemia, one might be tempted to call it a Type 1 (distal) renal tubular acidosis. Type 4 typically has a high potassium.

References

Batlle, Daniel C., et al. "The use of the urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis." New England Journal of Medicine 318.10 (1988): 594-599.

Corey, Howard E., Alfredo Vallo, and Juan Rodríguez-Soriano. "An analysis of renal tubular acidosis by the Stewart method." Pediatric Nephrology 21.2 (2006): 206-211.

Soriano, Juan Rodríguez. "Renal tubular acidosis: the clinical entity." Journal of the American Society of Nephrology 13.8 (2002): 2160-2170.

Karet, Fiona E. "Mechanisms in hyperkalemic renal tubular acidosis." Journal of the American Society of Nephrology 20.2 (2009): 251-254.

Batlle, D. C., S. Sabatini, and N. A. Kurtzman. "On the mechanism of toluene-induced renal tubular acidosis." Nephron 49.3 (1988): 210-218.

Question 3.1 - 2013, Paper 1

For each set of the following biochemical and arterial blood gas parameters:

  • Describe the abnormalities.
  • Give one example of an associated clinical scenario.

Any reasonable scenario accepted that was both biochemically correct AND clinically likely.

Test

Value

Normal Adult Range

Sodium

135 mmol/L

135 – 145

Potassium

4.0 mmol/L

3.2 – 4.5

Chloride

110 mmol/L

100 – 110

Bicarbonate*

3 mmol/L

24 – 32

pH*

7.10

7.35 – 7.45

pCO2*

10 mmHg (1.3 kPa)

35 – 45 (4.6 – 5.9)

College Answer

Increased anion gap and normal anion gap metabolic acidosis with appropriate respiratory compensation.

Clinical scenario – diabetic ketoacidosis with ketonuria or DKA with N saline resuscitation.

Discussion

Let us dissect these results systematically.

  1. The bits to calculate the A-a gradient are not supplied
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is not reported, but the bicarbonate is 3, suggesting a severe metabolic acidosis
  5. The respiratory compensation is roughly adequate - the expected PaCO2(3 × 1.5) + 8 = 12.5mmHg.
  6. The anion gap is raised:
    (135) - (110 + 3 ) = 22, or 26 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (22 - 12) / (24 - 3 ) = 0.47
    This delta ratio suggests that there is mixed high anion gap and normal anion gap metabolic acidosis here.
     

Situations which might give rise to such findings include

  • Lactic acidosis with concomitant overinfusion of normal saline
  • DKA in the process of therapy
  • Uremic renal failure

One of the below-listed references is from a journal which refers to some sort of small animal clinics. However, given that we share so many enzyme pathways, even in the setting of random mammal outpatients the basics of acid-base metabolism should be preserved.

References

Adams, L. G., and D. J. Polzin. "Mixed acid-base disorders." The Veterinary clinics of North America. Small animal practice 19.2 (1989): 307-326.

Walmsley, R. N., and G. H. White. "Mixed acid-base disorders." Clinical chemistry 31.2 (1985): 321-325.

Reddi, Alluru S. "Mixed Acid–Base Disorders." Fluid, Electrolyte and Acid-Base Disorders. Springer New York, 2014. 429-442

Question 3.2 - 2013, Paper 1

For each set of the following biochemical and arterial blood gas parameters:

  • Describe the abnormalities.
  • Give one example of an associated clinical scenario.

Any reasonable scenario accepted that was both biochemically correct AND clinically likely.

Test

Value

Normal Adult Range

Sodium

145 mmol/L

135 – 145

Potassium

4.0 mmol/L

3.2 – 4.5

Chloride*

91 mmol/L

100 – 110

Bicarbonate

30 mmol/L

24 – 32

pH*

7.62

7.35 – 7.45

pCO2*

30 mmHg (3.9 kPa)

35 – 45 (4.6 – 5.9)

College Answer

Increased anion gap, metabolic alkalosis and respiratory alkalosis.

Clinical scenario – salicylate overdose.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated - the information is missing
  2. There is alkalaemia
  3. The PaCO2 is not compensatory - its contributing to the alkalosis
  4. The SBE is not supplied, but the bicarbonate is 30, suggesting that there is a metabolic alkalosis
  5. The respiratory compensation is inadequate - the expected PaCO2(0.7 × 30) + 20 = 41mmHg, and thus there is also a respiratory alkalosis
  6. The anion gap is raised:
    (145) - (91  + 30) = 24, or 28 when calculated with potassium
    The delta ratio is irrelevant here.
  7. The urinary electrolytes and pH would not be helpful.

This is a mixed respiratory and metabolic alkalosis with a raised anion gap. There is only one beast which presents in this way: the salicylate overdose. To be precise, metabolic acidosis and respiratory alkalosis are characteristic of salicylate toxicity, and the metabolic alkalosis is some sort of unrelated sideshow. It is either due to torrential vomiting (which frequently accompanies salicylate intoxication) or due to the forced alkaline diuresis (which is the favoured method of enhancing salicylate clearance). Either way, all three acid-base disturbances are frequently seen together in the suicidal aspirin eater.

This level of discussion is probably sufficient for a question which was probably worth no more than 2 marks in a ten-mark question. These derangements of physiology are discussed in greater detail in the chapter on salicylate overdose from the "Acid-Base Disturbances" section.

References

TROLL, MARY, and MAUD L. MENTEN. "Salicylate poisoning: report of four cases." Archives of Pediatrics & Adolescent Medicine 69.1 (1945): 37.

Brubacher, Jeffrey R., and Robert S. Hoffman. "Salicylism from topical salicylates: review of the literature." Clinical Toxicology 34.4 (1996): 431-436.

Dargan, P. I., C. I. Wallace, and A. L. Jones. "An evidence based flowchart to guide the management of acute salicylate (aspirin) overdose." Emergency Medicine Journal 19.3 (2002): 206-209.

Gabow, Patricia A., et al. "Acid-base disturbances in the salicylate-intoxicated adult." Archives of Internal Medicine 138.10 (1978): 1481.

Rapoport, S., and George M. Guest. "The effect of salicylates on the electrolyte structure of the blood plasma. I. Respiratory alkalosis in monkeys and dogs after sodium and methyl salicylate; the influence of hypnotic drugs and of sodium bicarbonate on salicylate poisoning." Journal of Clinical Investigation24.5 (1945): 759.

Segar, William E., and Malcolm A. Holliday. "Physiologic abnormalities of salicylate intoxication." New England Journal of Medicine 259.25 (1958): 1191-1198.

Reddi, Alluru S. "Respiratory Alkalosis." Fluid, Electrolyte and Acid-Base Disorders. Springer New York, 2014. 421-428.

McQueen, D. S., Isobel M. Ritchie, and G. J. Birrell. "Arterial chemoreceptor involvement in salicylate‐induced hyperventilation in rats." British journal of pharmacology 98.2 (1989): 413-424.

Bhargava, K. P., O. M. Chandra, and D. R. Verma. "The mechanism of the emetic action of sodium salicylate." British journal of pharmacology and chemotherapy 21.1 (1963): 45-50.

Question 3.3 - 2013, Paper 1

For each set of the following biochemical and arterial blood gas parameters:

  • Describe the abnormalities.
  • Give one example of an associated clinical scenario.

Any reasonable scenario accepted that was both biochemically correct AND clinically likely.

Test

Value

Normal Adult Range

Sodium

145 mmol/L

135 – 145

Potassium

4.0 mmol/L

3.2 – 4.5

Chloride*

96 mmol/L

100 – 110

Bicarbonate

25 mmol/L

24 – 32

pH

7.42

7.35 – 7.45

pCO2

40 mmHg (5.2 kPa)

35 – 45 (4.6 – 5.9)

College Answer

Increased anion gap metabolic acidosis and metabolic alkalosis.

Clinical scenario – acute renal failure with vomiting .

Discussion

Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated - the information is missing
  2. There is a normal pH
  3. The PaCO2 is normal
  4. The SBE is not supplied, but the bicarbonate is 25, which is slightly higher than expected, suggestive of a metabolic alkalosis
  5. The respiratory compensation is inadequate - the expected PaCO2(0.7 × 25) + 20 = 37.5mmHg, and thus there is also a very mild respiratory acidosis
  6. The anion gap is raised:
    (145) - (96  + 25) = 24, or 28 when calculated with potassium
    The delta ratio is of no use here.
  7. The urinary electrolytes and pH would not be helpful.

Thus, this is a high anion gap metabolic acidosis with a coexisting metabolic alkalosis. Scenarios in which this might arise include the following:

  • Any cause of metabolic acidosis with a high anion gap  (eg. lactic acidosis, uremic acidosis, etc etc), as well as
    • vomiting / high NG aspirates
    • diuretic use
    • recovery from hypercapnea

References

Goodkin, David A., Gollapudi G. Krishna, and Robert G. Narins. "The role of the anion gap in detecting and managing mixed metabolic acid-base disorders."Clinics in endocrinology and metabolism 13.2 (1984): 333-349.

Question 3.1 - 2013, paper 2

A 24-year-old female with a history of depression presents with seizures and decreased consciousness. 

The following are her arterial blood gas analysis, taken on FiO2 0.3:.

Parameter

Patient Value

Normal Adult Range

Barometric pressure

760 mmHg (100 kPa)

pH

7.39

7.35 – 7.45

PCO2

40 mmHg (5.3 kPa)

35 – 45

PO2

110 mmHg (14.6 kPa)

Bicarbonate

24 mmol/L

22 – 27

Base Excess

-0.4 mmol/L

-2 – +2

Sodium

136 mmol/L

135 – 145

Potassium

4 mmol/L

3.5 – 4.5

Chloride

118 mmol/L*

110 – 110

Glucose

4.2 mmol/L

3.0 – 7.8

Lactate

0.8 mmol/L

0.5 – 2.2

a) What is the likely cause of her presentation? 

b) Give your reasoning.

College Answer

a) Lithium toxicity. 

b) Negative anion gap and history of depression.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is slightly raised:
    PAO2 = (0.3 × 713) - (40 × 1.25) = 163.9
    Thus, A-a = ( 163.9 - 110) = 53.9mmHg.
  2. There is no acidaemia
  3. The PaCO2 is normal
  4. The SBE is -0.4, suggesting a normal acid-base balance
  5. The respiratory compensation is irrelevant (bicarbonate is ideal)
  6. The anion gap is negative:
    (136) - (118 + 24) = -6, or -2 when calculated with potassium

There are few causes of negative anion gap.

The usual reason for such a result is an abundance of a cation which does not get measured in the normal biochemistry panels. Of these cations, lithium is the most commonly encountered in the clinical setting, followed by Polymyxin B. Halides such as bromide and iodide can cause a negative anion gap in spite of actually being anions themselves; however, by being chemically similar to chloride these ions tend to confuse the chloride-measuring electrode, "posing" as chloride in the laboratory and generating a spuriously elevated chloride value. Magnesium and calcium elevation can also result in a negative anion gap, but this is because they are not routinely included in the calculation of the gap.

Artifactual causes of a low or negative anion gap may include hyperlipidaemia and hypoalbuminaemia (although the "normal" anion gap value will merely trend towards zero with decreasing albumin levels- even without any albumin, the expected "normal" AG is 2.)

In short, the causes of a negative anion gap are as follows:

  • Increase in unmeasured cations
    • Lithium
    • Polymyxin B
    • Magnesium
    • Calcium
  • Interference with the measurement of chloride
    • iodide
    • bromide

References

 

Vasuvattakul, S. O. M. K. I. A. T., et al. "A negative anion gap as a clue to diagnose bromide intoxication." Nephron 69.3 (1995): 311-313.

Fischman, Ronald A., Gordon F. Fairclough, and Jhoong S. Cheigh. "Iodide and negative anion gap." The New England journal of medicine 298.18 (1978): 1035. - This one is not even available as an abstract! Atrocious, NEJM. Somebody want to send me a copy?..

O'Connor, Daniel T., and Richard A. Stone. "Hyperchloremia and negative anion gap associated with polymyxin B administration." Archives of internal medicine138.3 (1978): 478-480.

GRABER, MARK L., et al. "Spurious hyperchloremia and decreased anion gap in hyperlipidemia." Annals of internal medicine 98.5_Part_1 (1983): 607-609.

Kraut, Jeffrey A., and Nicolaos E. Madias. "Serum anion gap: its uses and limitations in clinical medicine." Clinical Journal of the American Society of Nephrology 2.1 (2007): 162-174.

Silverstein, Freya J., et al. "The effects of administration of lithium salts and magnesium sulfate on the serum anion gap." American Journal of Kidney Diseases 13.5 (1989): 377-381.

Question 3.3 - 2013, paper 2

The following blood results were obtained from a 63-year-old female in the ICU. She has septic shock, coagulopathy and requires renal replacement therapy. Her condition has deteriorated in the last few hours:

Parameter

Patient Value

Normal Adult Range

Sodium

136 mmol/L

135 – 145

Potassium

4.3 mmol/L

3.2 – 4.5

Chloride

104 mmol/L

100 – 110

Bicarbonate

14 mmol/L*

22 – 27

Urea

15.0 mmol/L*

3.0 – 8.0

Creatinine

0.34 mmol/L*

0.07 – 0.12

Total Calcium

2.4 mmol/L

2.15 – 2.6

Ionised Calcium

0.9 mmol/L*

1.1 -1.3

Phosphate

1.3 mmol/L

0.7 – 1.4

Albumin

26 G/L*

33 – 47

Globulins

35 G/L

25 – 45

Total Bilirubin

35 micromol/L*

4 – 20

Conjugated Bilirubin

30 micromol/L*

1 – 4

g-Glutamyl Transferase

120 U/L*

0 – 50

Alkaline Phosphatase

180 U/L*

40 – 110

Lactacte Dehydrogenase

3800 U/L*

110 – 250

Aspartate Aminotransferase

210 U/L*

< 40

Alanine Aminotransferase

400 IU/L*

< 40

  • What complication has occurred?
  • Give the reasons for your answer.

College Answer

  • Citrate toxicity secondary to regional citrate anticoagulation for CRRT.
  • Evidenced by:
    • High anionic gap metabolic acidosis
    • Low ionised calcium
    • High total:ionised calcium ratio
    • Liver impairment

Discussion

Let us calculate the anion gap.

(136) - (104 + 14) = 18, or 22.3 when calculated with potassium

Thus, it is raised by about 6 mEq/L.

Given the story of sepsis and renal failure, one would be prone to jump to conclusions (its lactate and uremia, you might say).

The hint is in the calcium.

The ionised calcium in acidosis normally increases. Well, in respiratory acidosis it probably increases more than in lactic acidosis (because lactate forms calcium-lactate complexes), but still - it should be high, not low. At this point the savvy candidate will detect a hint in the question - the patient is coagulopathic, and heparinisation of the dialysis circuit is probably a bad idea. They must be using citrate, one surmises.

This notion is confirmed by the presence of a high total to ionised calcium ratio (i.e. the total calcium is normal, but the ionised fraction is low - this is because measurement instruments which detect calcium will also measure citrate-calcium complexes in the serum, but the electrode which measures ionised calcium will only measure the free fraction, which decreases with citrate toxicity).

A homage to the interaction of pH and ionisation of calcium can be found in the section dedicated to acid-base disturbances.

References

LITFL have an excellent point-form summary of citrate toxicity. Much of what we know about it is derived from the sorry experience of patients who were recipients of massive transfusions.

Uhl, L., et al. "Unexpected citrate toxicity and severe hypocalcemia during apheresis." Transfusion 37.10 (1997): 1063-1065.

Bushinsky, David A., and Rebeca D. Monk. "Calcium." The Lancet 352.9124 (1998): 306-311.

Schaer, H., and U. Bachmann. "Ionized calcium in acidosis: differential effect of hypercapnic and lactic acidosis." British journal of anaesthesia 46.11 (1974): 842-848.

Dzik, Walter H., and Scott A. Kirkley. "Citrate toxicity during massive blood transfusion." Transfusion medicine reviews 2.2 (1988): 76-94.

Tolwani, Ashita J., et al. "Simplified citrate anticoagulation for continuous renal replacement therapy." Kidney international 60.1 (2001): 370-374.

Bakker, Andries J., et al. "Detection of citrate overdose in critically ill patients on citrate-anticoagulated venovenous haemofiltration: use of ionised and total/ionised calcium." Clinical Chemical Laboratory Medicine 44.8 (2006): 962-966.

Question 3.4 - 2013, paper 2

The following results were obtained from a 32-year-old male:

Parameter

Patient Value

Normal Adult Range

Plasma

Sodium

138 mmol/L

135 – 145

Potassium

3.4 mmol/L

3.4 – 5.0

Chloride

118 mmol/L*

100 – 110

Bicarbonate

15 mmol/L*

22 – 27

Arterial Blood Gas

FiO2

0.3

pH

7.32*

7.35 – 7.45

PO2

125 mmHg (16.4 kPa)

PCO2

30 mmHg (4 kPa)*

35 – 45 (4.6 – 6.0)

Base Excess

-10 mmol/L*

-2 – +2

Urine

pH

5.0

4.6 – 8.0

Sodium

40 mmol/L

Potassium

10 mmol/L

Chloride

80 mmol/L

a) Describe the abnormalities on the blood investigations.

b) What is the underlying mechanism for the primary abnormality?

College Answer

Answer

a)

A-a gradient of 50.

Normal anion gap metabolic acidosis with appropriate respiratory compensation.

b)

Mechanism is bicarbonate loss from GI tract as urinary anion gap is negative.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is 51.4:
    PAO2 = (0.3 × 713) - (30 × 1.25) = 176.4;
    thus A-a = (176.4 - 125) = 51.4
  2. There is acidaemia.
  3. The PCO2 is a compensatory response.
  4. The SBE is negative, suggesting that there is a metabolic acidosis
  5. The respiratory compensation is adequate:
    The expected CO2 is (15 × 1.5) + 8 = 30.5mmHg
  6. The anion gap is normal:
    (138) - (118 + 15) = 5, or 8.4 when calculated with potassium
  7. The urinary anion gap is (40+10) - 80 = -30

A low urinary anion gap suggests that there is no RTA, and that GI losses are responsible for the NAGMA.

But of course one could come to this conclusion by looking at the urine pH (which is near-maximally acidic, suggesting that appropriate renal compensation is taking place).

Thus, the mechanism must be gastrointestinal. Or, somebody has infused this 32-year-old male with an absurd excess of normal saline.

References

Batlle, Daniel C., et al. "The use of the urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis." New England Journal of Medicine 318.10 (1988): 594-599.

Question 7.1 - 2013, paper 2

A 65-year-old male has been brought into the Emergency Department after being found unconscious at home. He has a heart rate of 87 beats/min, a blood pressure of 96/59 mmHg, and temperature of 31.2°C.
Below is his biochemical profile and arterial blood gas analysis on a Hudson mask delivering 6 L/min oxygen:

Arterial Blood Gas:

 

Parameter

Patient Value

Normal Adult Range

pH

7.07*

7.35 – 7.45

PaO2

59 mmHg (7.8 kPa)*

PaCO2

25 mmHg (3.3 kPa)*

35 – 45 (4.6 – 6.0)

Bicarbonate

7 mmol/L*

22 – 26

Base Excess

-22 mmol/L*

-2 – +2

Lactate

0.8 mmol/L

< 2.0

Venous Biochemistry:

Parameter

Patient Value

Normal Adult Range

Sodium

133 mmol/L*

135 – 150 mmol/L

Potassium

6.2 mmol/L*

3.4 – 5.0

Chloride

94 mmol/L*

100 – 110

Urea

25.9 mmol/L*

3.0 – 8.0

Creatinine

271 mmol/L*

50 – 120

Total Bilirubin

13 mmol/L

< 20

Albumin

42 G/L

35 – 50

Alanine Aminotransferase

360 U/L*

< 35

Aspartate Aminotransferase

612 U/L*

< 40

g-Glutamyl Transferase

52 U/L*

< 40

Alkaline Phosphatase

123 U/L

35 – 135

Creatine Kinase

335 U/L*

30 – 140

Calcium (corrected)

2.65 mmol/L*

2.15 – 2.60

Magnesium

1.52 mmol/L*

0.7 – 1.10

Phosphate

3.91 mmol/L*

0.8 – 1.50

Glucose

10.5 mmol/L*

3.0 – 5.4

Ketones

6.6 mmol/L*

< 0.5

a) Describe the acid-base abnormalities seen in the arterial blood gas analysis.
b) List three possible causes of the ketosis.
c) What is the most likely cause? Give your reasoning.

College Answer

a) High anion gap metabolic acidosis (ketones and other unmeasured anion). Respiratory acidosis / inadequate respiratory compensation.

b) Alcoholic ketosis. Diabetic (euglycaemic) ketoacidosis. Starvation ketosis.

c) Alcoholic ketosis. Combination of severe AG acidosis with high level of ketones (too high for starvation ketosis) and abnormal liver enzymes (less likely with DKA).

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high; 194 or 337.6mmHg depending on what FiO2 you think the Hudson mask is delivering.
    PAO2 = (0.4 or 0.6 × 713) - (25 × 1.25) = 253 or 396.6
    Thus, A-a = ( 253 or 396.6 - 59) = 194 or 337.6mmHg.
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is -22, suggesting a severe metabolic acidosis
  5. The respiratory compensation is inadequate - the expected PaCO2(7 × 1.5) + 8 = 18.5mmHg, and thus there is also a respiratory acidosis
  6. The anion gap is raised:
    (133) - (94  + 7) = 32, or 38.2 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (32 - 12) / (24 - 7) = 1.17
    This suggests that there is a pure high anion gap metabolic acidosis here.
     

The lactate cannot account for this, and the renal failure - though severe - is insufficiently severe to serve as an explanation for such a raised anion gap. Ketones remain as the only explanation.

The college asks for three differentials for ketosis, which is helpful (because there only three major types):

  • Alcoholic ketoacidosis
  • Starvation ketoacidosis
  • Diabetic ketoacidosis

Ketoacidosis mechanisms and management strategies for DKA are discussed elsewhere.

This patient is probably a veteran drinker. As the college points out, starvation ketoacidosis does not tend to have such a high ketone level, and DKA patients are unlikely to have such abnormal LFTs.

References

UpToDate has a nice summary of this topic for the paying customer.

Oh's Intensive Care manual: Chapter 58  (pp. 629) Diabetic  emergencies  by Richard  Keays

Umpierrez, Guillermo E., Mary Beth Murphy, and Abbas E. Kitabchi. "Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome." Diabetes Spectrum15.1 (2002): 28-36.

ARIEFF, ALLEN I., and HUGH J. CARROLL. "Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of theraphy in 37 cases." Medicine 51.2 (1972): 73-94.

Alberti, K. G. M. M., et al. "Role of glucagon and other hormones in development of diabetic ketoacidosis." The Lancet 305.7920 (1975): 1307-1311.

Kitabchi, Abbas E., et al. "Management of hyperglycemic crises in patients with diabetes." Diabetes care 24.1 (2001): 131-153.

Foster, Jennifer Ruth, Gavin Morrison, and Douglas D. Fraser. "Diabetic ketoacidosis-associated stroke in children and youth." Stroke research and treatment 2011 (2011).

Edge, J. A., et al. "The risk and outcome of cerebral oedema developing during diabetic ketoacidosis." Archives of disease in childhood 85.1 (2001): 16-22.

Woodrow, G., A. M. Brownjohn, and J. H. Turney. "Acute renal failure in patients with type 1 diabetes mellitus." Postgraduate medical journal 70.821 (1994): 192-194.

Bonfanti, R., et al. "Disseminated intravascular coagulation and severe peripheral neuropathy complicating ketoacidosis in a newly diagnosed diabetic child." Acta diabetologica 31.3 (1994): 173-174.

Chua, Horng-Ruey, et al. "Plasma-Lyte 148 vs 0.9% saline for fluid resuscitation in diabetic ketoacidosis." Journal of critical care 27.2 (2012): 138-145.

Stowe, Michele L. "Plasma-Lyte vs. Normal Saline: Preventing Hyperchloremic Acidosis in Fluid Resuscitation for Diabetic Ketoacidosis." (2012).

Jivan, Daksha. "A comparison of the use of normal saline versus Ringers lactate in the fluid resuscitation of diabetic ketoacidosis." (2013).

Basnet, Sangita, et al. "Effect of Normal Saline and Half Normal Saline on Serum Electrolytes During Recovery Phase of Diabetic Ketoacidosis." Journal of intensive care medicine 29.1 (2014): 38-42.

Hillman, K. "Fluid resuscitation in diabetic emergencies—a reappraisal."Intensive care medicine 13.1 (1987): 4-8.

Wagner, Arnd, et al. "Therapy of severe diabetic ketoacidosis. Zero-mortality under very-low-dose insulin application." Diabetes care 22.5 (1999): 674-677.

Chiasson, Jean-Louis, et al. "Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state." Canadian Medical Association Journal 168.7 (2003): 859-866.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes a consensus statement from the American Diabetes Association." Diabetes care 29.12 (2006): 2739-2748.

Question 7.2 - 2013, paper 2

A 50-year-old Scottish male tourist presents with a three-day history of nausea, vomiting, general lethargy and dizziness. He had similar symptoms one year previously while on holiday in Cyprus and has had multiple presentations to his GP since then with general lethargy and weight loss.
The results of his investigations are as follows:

Parameter

Patient Value

Normal Adult Range

FiO2

0.3

pH

7.29*

7.35 – 7.45

pCO2

22 mmHg (2.9 kPa)

35 – 45 (4.6 – 6.0)

PO2

108 mmHg

SaO2

99%

Bicarbonate

11 mmol/L*

22 – 26

Base Excess

-14 mmol/L*

-2 – +2

Lactate

0.8 mmol/L

< 2.0

Sodium

116 mmol/L*

135 – 150

Potassium

4.7 mmol/L

3.4 – 5.0

Chloride

89 mmol/L*

100 – 110

Urea

1.3 mmol/L*

3.0 – 8.0

Creatinine

40 mmol/L*

50 – 120

Glucose

4.8 mmol/L

3.0 – 5.4

Albumin

39 G/L

35 – 50

Calcium (corrected)

2.08 mmol/L*

2.15 – 2.64

 

a) What is the likely diagnosis?
b) What investigation would you order to confirm your diagnosis?

College Answer

a)  Hypoadrenalism or Addisonian crisis.

b)  Random cortisol.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high; 78.4mmHg
    PAO2 = (0.3 × 713) - (22 x 1.25) = 186.4
    Thus, A-a = (186.4 - 108) = 78.4mmHg.
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is -14, suggesting a severe metabolic acidosis
  5. The respiratory compensation is adequate - the expected PaCO2(11 x 1.5) + 8 = 24.5mmHg, and the measured 22mmHg is close enough for government work.
  6. The anion gap is raised:
    (116) - (89  + 11) = 16, or 20.7 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (16 - 12) / (24 - 11) = 0.3
    This suggests that there is a normal anion gap metabolic acidosis here, with just a hint of HAGMA.
  7. Urinary pH or electrolytes are not available.

There is a severe mixed metabolic acidosis with severe hyponatremia and moderate hypocalcemia, in the presence of a normal lactate and normal renal function. Hyperglycaemia is not to blame - the BSL is 4.8

If the patient had a higher serum potassium, the diagnosis of Addisonian crisis would be easier to conjure. Addison's disease is discussed briefly in the chapter on adrenal insufficiency; it causes a Type 4 renal tubular acidosis by interfering with the actions of aldosterone at the cortical collecting duct.

As for the anion gap? I cannot explain that. Nor can I explain why this patient had to be a Scotsman, or the involvement of Cyprus.

And yes, to confirm hypoadrenalism, one would ask for a random cortisol, as well as a short synacthen test.

References

Corey, Howard E., Alfredo Vallo, and Juan Rodríguez-Soriano. "An analysis of renal tubular acidosis by the Stewart method." Pediatric Nephrology 21.2 (2006): 206-211.

Soriano, Juan Rodríguez. "Renal tubular acidosis: the clinical entity." Journal of the American Society of Nephrology 13.8 (2002): 2160-2170.

Karet, Fiona E. "Mechanisms in hyperkalemic renal tubular acidosis." Journal of the American Society of Nephrology 20.2 (2009): 251-254.

Question 18.2 - 2013, paper 2

A 19-year-old male with a history of substance abuse presents to the Emergency Department with respiratory distress.

Parameter

Patient Value

Normal Adult Range

FiO2

0.4

pH

6.94*

7.35 – 7.45

PO2

140 mmHg (18.4 kPa)

PCO2

17* mmHg (2.2 kPa)

35 – 45 (4.6 – 6.0)

HCO3

4* mmol/L

22 – 27

Base Excess

-28 mmol/L*

-2.0 – +2.0

Sodium

127* mmol/L

135 – 145

Chloride

113* mmol/L

95 – 105

Potassium

3.9 mmol/L

3.5 – 5.0

Urine pH

7.2

4.6 – 8.0

a)Describe the acid-base disturbance.

b)What is the likely cause of the acid-base disturbance?

College Answer

a) Normal anion gap severe metabolic acidosis with incomplete compensation.

b) Renal tubular acidosis Type 1 distal secondary to chronic toluene abuse.

 

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high; ~127mmHg
    PAO2 = (0.4 × 713) - (17 × 1.25) = 266.95
    Thus, A-a = (266.95 - 140) = 126.95mmHg.
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is -28, suggesting a severe metabolic acidosis
  5. The respiratory compensation is slightly less than adequate - the expected PaCO2(4 × 1.5) + 8 = 14mmHg, and the measured 17mmHg is just outside the +/- 2mmHg error range for Winter's Rule.
  6. The anion gap is essentially normal:
    (127) - (113 + 4) = 10, or 13.9 when calculated with potassium
  7. Urinary electrolytes are not available, but the pH is 7.2 - in fact its even more alkaline than the blood pH!

A result like this has you asking, what the hell are the kidneys doing? Why are they not acidifying the urine? The answer may lay in the history of this young man's substance abuse. One may eventually arrive at the conclusion that he is a connoisseur of volatile solvents.

The recreational enjoyment of toluene can lead to a nasty Type 1 (distal) renal tubular acidosis.

References

Batlle, D. C., S. Sabatini, and N. A. Kurtzman. "On the mechanism of toluene-induced renal tubular acidosis." Nephron 49.3 (1988): 210-218.

Question 18.3 - 2013, paper 2

The following blood results are from a 78-year-old female with Type 2 diabetes and chronic renal failure presenting with breathlessness. Her GP has been treating her with flucloxacillin for cellulitis of her lower limbs.

Parameter

Patient Value

Normal Adult Range

Urea

15.3 mmol/L*

3 – 8

Creatinine

309 μmol/L*

45–90

Sodium

139 mmol/L

134 – 146

Potassium

4.4 mmol/L

3.4 – 5.0

Chloride

115 mmol/L*

100 – 110

Glucose

12.1 mmol/L*

3.0 – 5.4

pH

7.11*

7.35– 7.45

PCO2

13 mmHg (1.7 kPa)*

35– 45 (4.6 – 6.0)

Bicarbonate

4 mmol/L*

22–27

Base Excess

-24 mmol/L*

-2 – +2

Lactate

0.6 mmol/L

< 2.0

Measured osmolality

309 mOsm/L*

280 – 300

a) Describe the acid-base abnormalities in the above results.

b) List three possible causes for this biochemical disturbance.

College Answer

a) Severe compensated metabolic acidosis with a raised anion gap (! 20), normal osmolar gap and Δ gap 0.4 (Δ gap suggests mixed AG and NAG MA or renal failure)

b)Possible causes

    • DKA
    • Renal failure
    • Pyroglutamic acidosis

Discussion

Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated.
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is -24, suggesting a severe metabolic acidosis
  5. The respiratory compensation is adequate. 
    The expected PaCO2(4 × 1.5) + 8 = 14mmHg.
  6. The anion gap is raised:
    (139) - (115 + 4) = 20, or 24.4 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (20 - 12) / (24 - 4) = 0.4
    This suggests that there is a mixed high anion gap and normal anion gap metabolic acidosis here.
     
  7. The urinary pH and electrolytes are not supplied here.

However, we are supplied with a measured osmolality, which is high - 309 mOsm/L. Is there an osmolar gap? If we calculate the osmolality from the EUCs, we arrive at a value of (139 × 2 + urea + glucose) = 305.4 mOsm/L. So... there is no osmolar gap.

Thus, the only possible explanations must be

  • Renal failure
  • DKA
  • Pyroglutamic acidosis (the college mentioned flucloxacillin, and thus to omit this one from the list of differentials would be amiss)

References

Warnock DG. Uremic acidosis. Kidney Int. 1988 Aug;34(2):278-87.

Relman, Arnold S., Edward J. Lennon, and Jacob Lemann Jr. "Endogenous production of fixed acid and the measurement of the net balance of acid in normal subjects." Journal of Clinical Investigation 40.9 (1961): 1621.

Laffel, Lori. "Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes." Diabetes/metabolism research and reviews 15.6 (1999): 412-426.

Elisaf, Moses S., et al. "Acid-base and electrolyte disturbances in patients with diabetic ketoacidosis." Diabetes research and clinical practice 34.1 (1996): 23-27.

Dempsey GA Lyall HJ, Corke CF, Scheinkestel CD. Pyroglutamic acidemia: a cause of high anion gap metabolic acidosis. Crit Care Med. 2000Jun;28(6):1803-7.

Duewall, Jennifer L., et al. "5-Oxoproline (pyroglutamic) acidosis associated with chronic acetaminophen use." Proceedings (Baylor University. Medical Center) 23.1 (2010): 19.

Akhilesh Kumar and Anand K. Bachhawat Pyroglutamic acid: throwing light on a lightly studied metabolite ,SPECIAL SECTION: CHEMISTRY AND BIOLOGY. CURRENT SCIENCE, VOL. 102, NO. 2, 25 JANUARY 2012. 288

Question 23 - 2013, paper 2

A 37-year-old previously healthy man was admitted to your ICU five days ago after a motor vehicle crash with chest and abdominal injuries. He is currently intubated and ventilated, with FIO2 1.0 and PEEP 10 cmH2O. He is deeply sedated and on noradrenaline and adrenaline infusions at 10mcg/min each. He has become oliguric.

His blood biochemistry, haematology and arterial blood gases are as follows

Venous Biochemistry


Test

Value

Normal Adult Range

Sodium

138 mmol/L

135 – 145

Potassium

7.1 mmol/L*

3.5 – 4.5

Chloride

104 mmol/L

95 – 105

Urea

27 mmol/L*

2.9 – 8.2

Creatinine

260 μmol/L*

70 – 120

Haematology


Test

Value

Normal Adult Range

Haemoglobin

120 G/L*

135 -180

White Blood Cells

12.8 x 109/L*

4.0 -11.0

Platelets

42 x 109/L*

140 - 400

Arterial Blood Gases


Test

Value

Normal Adult Range

pH

7.01*

7.35 – 7.45

PCO2

45 mmHg (6 kPa)

35 – 45 (4.6 – 6.0)

PO2

70 mm Hg (9.3 kPa)*

Bicarbonate

11 mmol/L*

22 - 26

Base Excess

-19 mmol/L*

-2.0 – + 2.0

Glucose

7.5 mmol/L*

4 – 6

Lactate

13 mmol/L*

< 2.0

a) Summarise the findings of the blood tests.

b) List the likely causes of the raised lactate.

c) Briefly outline your management priorities for this man.

College Answer

a)

  • High anion gap metabolic acidosis Note AG 33 - NOT adequately explained just by a lactate of 13 mmol. Delta ratio approx. 2
  • Inadequate or inappropriate respiratory compensation
  • Hypoxaemia (P/F ratio 70)
  • Acute renal failure
  • Hyperkalaemia,
  • Thrombocytopenia
  • Anaemia
  • Leukocytosis
  • Mild hyperglycaemia (? Stress-induced)

b)

  • Sepsis with shock
  • Ongoing hypovolaemia
  • Hypoperfusion eg septic cardiomyopathy; abdominal compartment syndrome
  • Possible gut ischemia
  • Perhaps adrenaline (also seen with other catecholamines – unpredictable)

c)

Management Priorities should encompass both immediate resuscitation and investigation for the cause of the abnormalities.

Respiratory:

Clinical examination and CXR looking for cause of hypoxia – consider lung contusion, haemothorax/pneumothorax with shock, ARDS secondary to other process. Institute ARDS ventilation strategy if appropriate.

Cardiovascular:

Clinical examination and further investigations to determine cause of inotrope and vasopressor requirement. Consider ECHO. Fluid resuscitation if hypovolaemia suggested by examination /ECHO findings.

Cease adrenaline if possible.

Renal

Emergency management of hyperkalaemia – calcium, bicarbonate, dextrose, insulin, followed by institution of renal replacement therapy.

Examination and investigation for cause of deterioration:

Abdominal examination and measurement of intrabadominal pressures Examination for potential sources of infection, including GI, lines, ventilator acquired

pneumonia, wounds, urine. Consider empirical antibiotic treatment if thought to be septic aetiology.

Serum lipase, troponin, CK, blood cultures. 
Examination to exclude limb compartments, rhabdomyolysis.

Imaging as suggested by results of examination – may require abdominal/thoracic CT scan, renal USS if anuric, angiography/endoscopy if evidence of ongoing bleeding.

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is very high; 194 or 337.6mmHg depending on what FiO2 you are delivering.
    PAO2 = (1.0 × 713) - (45 × 1.25) = 656.75
    Thus, A-a = (656.75 - 70) = 586.75mmHg.
  2. There is acidaemia
  3. The PaCO2 is not compensatory, suggesting there is respiratory acidosis
  4. The SBE is -19, suggesting there is also a severe metabolic acidosis
  5. The respiratory compensation is totally lacking - the expected PaCO2(11 × 1.5) + 8 = 24.5mmHg, and thus there is also a significant respiratory acidosis
  6. The anion gap is raised:
    (138) - (104 + 11) = 23, or 30.1 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (23 - 12) / (24 - 11) = 0.84
    This suggests that there is mainly a high anion gap metabolic acidosis here, with some minor contribution from a normal anion gap acidosis. It is not accounted for by the lactate (13mmol/L)
  7. Urinary pH and electolytes are not reported, and are irrelevant.

Thus, in summary there is both a respiratory acidosis and a HAGMA, which is only partially related to lactate.

On top of that, the patient is severy hypoxic, thrombocytopenic, hyperkalemic, and in renal failure with uremia.

The likely causes of raised lactate are

  • Shock
  • Hypoxia
  • Gut ischaemia
  • Microvascular shunting due to sepsis
  • The use of adrenaline

In general, the causes of lactic acidosis are discussed at great length elsewhere.

The management priorities - if one were going to approach this with some sort of system - would resemble the following list:

Airway

  • Investigate ETT malfunction as a cause of hypoxia and hypercapnea (i.e. is it kinked, or leaking?)

Ventilation

  • Hypoxia needs to be investigated; potential causes include
    • ARDS
    • Lung contusion
    • Pneumothorax / haemothorax
  • These can be excluded with a quick bedside ultrasound and mobile CXR
  • Thereafter, one may adjust the ventilator accoridngly (eg. increase resp rate, go to 1:1 I:E ratio, increase the PEEP, decrease the tidal volume, practicing lung protective ventilation)

Circulation

Shock state needs to be investigated; potential causes include

  • Hypovolemia
  • Cardiogenic "pump failure" (eg. due to contusions or cardiac tamponade)
  • Vasoplegia (due to sepsis)

A TTE can rule out many of these causes.

Thereafter, it would be helpful to wean off adrenaline, and if need be change over to a non-catecholamine inotrope (eg. milrinone).

Sedation and paralysis

  • Neuromuscular blockade may improve ventilation

Electrolytes

  • Hyperkalemia needs immediate attention. Calcium gluconate and an insulin/dextrose bolus need to be administered, and bicarbonate should be considered (but it may impair the metabolism of lactate)

Fluid balance

  • CVVHDF should commence to correct the uremia and manage the hyperkalemia
  • Depending on dynamic assessment of fluid responsiveness, further fluids may be necessary

Abdominal injuries

  • Abdominal compartment pressure should be measured
  • A surgical opinion should be sought regarding mesentric ischaemia as the cause of the lactic acidosis
  • A serum lipase and LFTs should be sent to rule out pancreatitis and hepatic dysfunction as causes of the hyperlactataemic shock state.

Haematological disturbances

  • Hb should be checked at regular intervals to screen for non-obvious internal blood loss (eg. a retroperitoneal hematoma or aortic dissection)
  • A PR should be performed to look for melaena
  • The coagulation parameters should be measured
  • CoAgulopathy should be corrected if invasive procedures are planned or if bleeding is suspected

Infectious complications

  • A septic screen should be sent
  • Line sites and wounds should be inspected
  • If no evidence of infection is discovered, empirical antibiotics are not indicated.
 

References

Luft FC. Lactic acidosis update for critical care clinicians. J Am Soc Nephrol 2001 Feb; 12 Suppl 17 S15-9.

Ohs manual – Chapter 15 by D J (Jamie) Cooper and Alistair D Nichol, titled “Lactic acidosis” (pp. 145)

Cohen RD, Woods HF. Lactic acidosis revisited. Diabetes 1983; 32: 181–91.

Lange, H., and R. Jäckel. "Usefulness of plasma lactate concentration in the diagnosis of acute abdominal disease." The European journal of surgery= Acta chirurgica 160.6-7 (1994): 381.

WEIL, MAX HARRY, and ABDELMONEN A. AFIFI. "Experimental and clinical studies on lactate and pyruvate as indicators of the severity of acute circulatory failure (shock)." Circulation 41.6 (1970): 989-1001.

Question 26.1 - 2013, paper 2

The following results are from the arterial blood gas analysis of a 46-year-old male ventilated in ICU for three weeks with severe community-acquired pneumonia and ARDS:

Parameter

Patient Value

Normal Adult Range

FiO2

0.6

pH

7.5*

7.35 – 7.45

PO2

79.0 mmHg (10.5 kPa)

PCO2

45.0 mmHg (6.0 kPa)

35 – 45 (4.6 – 6.0)

Bicarbonate

36 mmol/L*

22 – 27

Base Excess

12 mmol/L*

-2.0 – +2.0

Sodium

138 mmol/L

135 – 145

Potassium

5.0 mmol/L

3.5 – 5.0

Chloride

97 mmol/L

95 – 105

a) Describe the abnormalities.

b) Give one likely cause.

College Answer

a)

Metabolic alkalosis (PCO2 appropriate using 0.7 x [HCO3] + 20 +/- 5) A-a DO2 = 295 (P/F 130 “moderate” ARDS)

b)

  • Resolution of primary respiratory acidosis with delayed correction of metabolic compensation
  • Diuretic therapy

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high:
    PAO2 = (0.6 x 713) - (45 x 1.25) = 371.55
    Thus, A-a = 292.55mmHg
  2. There is alkalaemia
  3. The PaCO2 is compensatory (increased, though still within the normal range)
  4. The SBE is 12, suggesting a metabolic alkalosis
  5. The respiratory compensation is adequate - the expected PaCO2(36× 0.7) + 20 = 45.2mmHg
  6. The anion gap is normal:
    (138) - (97  + 36) = 5, or 10 when calculated with potassium
  7. The urinary electrolytes and pH are irrelevant.

Thus, this patient has a metabolic alkalosis with respiratory compensation.

This is either a recovery from chronic respiratory acidosis, or the evidence of loop diuretic treatment.

Either is equally likely given this ARDS story.

 

References

Khanna, Apurv, and Neil A. Kurtzman. "Metabolic alkalosis." J NEPHROL 2006; 19 (suppl 9): S86-S96

Question 26.2 - 2013, paper 2

A 75-year-old female insulin-dependent diabetic presents to the Emergency Department semi-comatose. She has been unwell for several days and has a past medical history of left ventricular failure treated with digoxin and a thiazide diuretic.

The following data are from arterial blood gas analysis on admission:

Parameter

Patient Value

Normal Adult Range

FiO2

0.4

pH

7.40

7.35 – 7.45

PO2

82.0 mmHg (10.8 kPa)

PCO2

32.0 mmHg (4.2 kPa)*

35 – 45 (4.6 – 6.0)

Bicarbonate

19 mmol/L*

22 – 27

Potassium

2.7 mmol/L*

3.5 – 5.0

Glucose

67 mmol/L*

3.0 – 7.8

Anion Gap

34 mmol/L*

7 – 17

Interpret the acid-base disturbance and give your reasoning.

College Answer

  • High AG implies severe metabolic acidosis
  • ∆ Ratio > 3 indicates pre-existing metabolic alkalosis
  • PCO2 slightly lower than expected for compensation (1.5 x [HCO3] + 8) implying mild respiratory alkalosis
  • History suggests DKA and K+ depletion secondary to diuretic use
  • Severe compensated metabolic acidosis 2° DKA with mild respiratory alkalosis and pre-existing metabolic alkalosis

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high:
    PAO2 = (0.4 × 713) - (32 × 1.25) = 173.8
    Thus, A-a = 91.8 mmHg.
  2. There is a normal pH
  3. The PaCO2 is low, suggesting a respiratory alkalosis
  4. The SBE is not given but the bicarbonate is 19mmol/L, suggesting a metabolic acidosis
  5. The respiratory compensation is excessive - the expected PaCO2(19 × 1.5) + 8 = 36.5mmHg, confirming that there is also a respiratory alkalosis
  6. The anion gap is raised, and the college gave it to us (34)
    The delta ratio suggests that there is a pure high anion gap metabolic acidosis here, on the background of a metabolic alkalosis
    (34 - 12) / (24 - 19) = 4.4

So. What can account for such a massively raised anion gap?

Well. Firstly, the anion gap may be calculated incorrectly. One is not given a sodium value, and one wonders whether whoever calculated the anion gap corrected the sodium for hyperglycaemia. If one did this to only sodium and neglected all the other electrolytes, the anion gap would grow larger. In any case, there would be no point; the correction of sodium is really only a measure of dehydration, and a guard against unintelligent sodium replacement.

The extreme hyperglycaemia lends itself to the idea that a HONK state may be present. This is supported by the history - this patient is a diabetic who has been neglecting herself. However, she is an IDDM, which suggests that this is simply an extremely dehydrated DKA situation. The two conditions frequently overlap, after all. The low potassium supports this idea of severe dehydration; likely, while eschewing insulin, she continued to dutifully take her thiazides. The diuretics also explain the chronic metabolic alkalosis (if it were not the case, by this stage any self-respecting DKA patient would have a HCO3- level in the single digits).

 

References

Chiasson, Jean-Louis, et al. "Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state." Canadian Medical Association Journal 168.7 (2003): 859-866.

Lim, K. C., and C. H. Walsh. "Diabetic ketoalkalosis: a readily misdiagnosed entity." British medical journal 2.6026 (1976): 19.

Question 26.3 - 2013, paper 2

A 59-year-old male with a past medical history of hypertension and dyslipidaemia presents with sore muscles, jaundice and oliguria.

The following data are taken from venous blood investigations on his admission:

Parameter

Patient Value

Normal Adult Range

Urea

25.5 mmol/L*

3.0 – 8.0

Creatinine

523 μmol/L*

45 – 90

Sodium

138 mmol/L

134 – 145

Potassium

6.2 mmol/L*

3.4 – 5.0

Chloride

105 mmol/L

98 – 108

Bicarbonate

16 mmol/L*

22 – 32

Calcium (corrected)

2.07 mmol/L*

2.20 – 2.55

Phosphate

1.6 mmol/L*

0.8 – 1.5

Creatine Kinase

60110 U/L*

< 200

Bilirubin

108 μmol/L*

< 20

Alkaline Phosphatase

221 U/L*

35 – 135

Alamine Aminotransferase

1073 U/L*

< 40

g-Glutamyl Transferase

437 U/L*

< 60

Albumin

29 G/L*

35 – 50

a)  What is the diagnosis?

b)  Give four likely causes in this patient.

College Answer

a) Rhabdomyolysis.

b)

  • Muscle ishaemia / compartment syndrome secondary to peripheral vascular disease
  • Infection
  • Drugs / toxins e.g. statins, alcohol
  • Inflammatory myopathies
  • Endocrine disorders

Discussion

This question could just as easily have been slotted into the electrolyte disturbance section or the renal failure section. The patient plainly has rhabdomyolysis. The college were looking for a single-word answer. The decreased bicarbonate indeed suggests that a metabolic acidosis is in play, and it is a high anion gap sort of thing, with probably some combination of uremic, lactic and normal anion gap acidosis (given that the anion gap is (138) - (105 + 16) = 17, or 23.2 when calculated with potassium, and the delta ratio is (17 - 12) / (24 - 16) = 0.62.)

More interestingly, what could have caused it?

The general breakdown of differentials is as follows:

  • Vascular - muscle ischaemia, eg. ischaemic limb, or myocardial infarction
  • Infectious - eg. necrotising fasciitis
  • Neoplastic , eg. sarcoma
  • Drug-related , eg. due to MDMA or statins, or due to neuroleptic-malignant syndrome
  • Congenital, eg. some sort of congenital myopathy
  • Autoimmune , eg polymyositis or dermatomyositis
  • Traumatic, eg. crush injury, blast injury, compartment syndrome, immobilityetc
  • Environmental , eg. hyperthermic injury, "heat stroke"
  • Endocrine , eg. hyperthyroidism or phaeochromocytoma

Rhabdomyolysis is discussed at greater length in the discussion of Question 16 from the first paper of 2008.

References

Allison, Ronald C., and D. Lawrence Bedsole. "The other medical causes of rhabdomyolysis." The American journal of the medical sciences 326.2 (2003): 79-88.

Question 26.4 - 2013, paper 2

A 68-year-old Type 2 diabetic with a history of alcohol abuse is admitted with abdominal pain and the following results:

Parameter

Patient Value

Normal Adult Range

pH

6.87*

7.35 - 7.45

PaCO2

8 mmHg (1.1 kPa)*

35 - 45 (4.7-6.0 kPa)

PaO2

149 mmHg (20 kPa)

Bicarbonate

1.4 mmol/L*

22 – 26

Lactate

16 mmol/L*

< 2

Sodium

142 mmol/L

134 – 145

Potassium

4.7 mmol/L

3.5 – 5.1

Chloride

107 mmol/L*

95 – 105

Urea

14 mmol/L*

3.4 – 8.9

Creatinine

170 μmol/L*

60 – 110

Aspartate Aminotransferase

60 U/L*

< 40

Alanine Aminotransferase

70 U/L*

< 40

Lactate Dehydrogenase

1400 U/L*

50 - 150

Total bilirubin

20 μmol/L

< 20

Glucose

6.5 mmol/L*

3.0 – 5.4

Serum osmolality

314 mOsm/kg*

275 – 295

a) Give three likely diagnoses.

b) List two additional investigations that you would perform based on the above information.

College Answer

a)

  • Ischaemic bowel
  • Metformin induced lactic acidosis
  • Cardiogenic shock 
  • Thiamine deficiency
  • Pancreatitis
  • OR Any reasonable diagnosis

b)

  • Two of the following investigations:
    • Diagnostic laparoscopy or laparotomy
    • CT abdomen
    • Troponin
    • Red cell transketolase,
    • Lipase

Discussion

Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated, as no FiO2 is supplied to us
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is not supplied, but the bicarbonate is 1.4, suggesting a severe metabolic acidosis
  5. The respiratory compensation is adequate and lurks around the natural limits of human respiratory compensation for metabolic acidosis- the expected PaCO2(1.4 × 1.5) + 8 = 10.1mmHg
  6. The anion gap is raised:
    (142) - (107 + 1.) = 34, or 38.7 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (34 - 12) / (24 - 1.) = 0.95 (.e. mainly a high anion gap acidosis)
  7. Urinary pH and electrolytes are not supplied, and are irrelevant.

So, what is making this diabetic drunk so acidotic?

Well, the lactate of 16 is probably contributing. But it does not account for the whole of the anion gap.

The college kindly gives us a measured osmolality, so we can calculate the osmolar gap:

314 - (142 × 2 + 14 + 6.5) = 9.5

Thus, toxic alcohol ingestion (eg. ethylene glycol or methanol) is less likely.

Three likely culprits of any of the below causes is all the college wanted, or any reasonable diagnosis.

  • Alcoholic ketoacidosis
  • Lactic acidosis due to gut ischaemia
  • Lactic acidosis due to biguanide use
  • Lactic acidosis due to thiamine deficiency
  • Lactic acidosis due to maligancy
  • Pancreatitis
  • Cardiogenic shock
  • Sepsis

Thus, investigations could include any two of the following:

References

Smeets, E. H. J., H. Muller, and J. De Wael. "A NADH-dependent transketolase assay in erythrocyte hemolysates." Clinica chimica acta 33.2 (1971): 379-386.

Lonsdale, Derrick, and Raymond J. Shamberger. "Red cell transketolase as an indicator of nutritional deficiency." The American journal of clinical nutrition 33.2 (1980): 205-211.

FENNELLY, JAMES, et al. "Red blood cell-transketolase activity in malnourished alcoholics with cirrhosis." The American journal of clinical nutrition 20.9 (1967): 946-949.

Talwar, Dinesh, et al. "Vitamin B1 status assessed by direct measurement of thiamin pyrophosphate in erythrocytes or whole blood by HPLC: comparison with erythrocyte transketolase activation assay." Clinical chemistry 46.5 (2000): 704-710.

Rossouw, J. E., et al. "Red blood cell transketolase activity and the effect of thiamine supplementation in patients with chronic liver disease." Scandinavian journal of gastroenterology 13.2 (1978): 133-138.

Question 7.2 - 2014, Paper 1

List three causes for the following combination of findings observed on a serum sample:

Parameter

Patient Value

Normal Adult Range

Measured osmolality

340 mOsm/kg*

280 – 290

Sodium

138 mmol/L

135 – 145

Potassium

4.0 mmol/L

3.5 – 5.0

Chloride

98 mmol/L

95 – 105

Bicarbonate

15 mmol/L*

22 – 32

Glucose

6.0 mmol/L

4.0 – 6.0

Urea

8.0 mmol/L

6.0 – 8.0

College Answer

Raised osmolar gap with raised AG
Methanol
Ethylene glycol
Ethanol
(Lactic acidosis can lead to a raised OG and AG; however, the osmolar gap does not reach the levels seen here.)

Discussion

Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated.
  2. There is no pH measurement; one assumes that there must be an acidaemia because the bicarbonate value is low.
  3. The PaCO2 is not available, and it is therefore impossible to assess respiratory compensation
  4. The SBE is not reported.
  5. The respiratory compensation is irrelevant (see point 3).
  6. The anion gap is  raised:
    (138) - (98  + 15) = 25, or 29 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (25 - 12) / (24 - 15) = 1.44
    This  suggests a pure high anion gap metabolic acisosis:
  7. The osmolar gap is raised:
    Calculated osmolality is  (2×138) + (8 + 6) = 290 mOsm/L;
    whereas the measured osmolality is 340 mOsm/L, giving us a gap of 50mOsm.

So, what could account for this? Where did the extra osmoles come from?

Fortunately, Jeffrey Kraut comes to the rescue once again with an article which seems tailored to answering this question. In brief, there are a few situations which could cause the simultaneous increase of both the anion gap and the osmolar gap. Kraut lists the following as well-recognised causes:

Toxicological causes

  • Methanol intoxication
  • Ethylene glycol intoxication
  • Diethylene glycol intoxication
  • Propylene glycol intoxication
  • Isopropanol intoxication
  • Salicylate intoxication

Endocrine and metabolic disturbances

  • Lactic acidosis
  • Alcoholic or diabetic ketoacidosis
  • Acute kidney injury

Kraut also cautions us to respect the timeframe of toxic exposure. When one quaffs a facefull of methanol, one imbibes a substance which is not dissociated at physiological pH: methanol has a pKa of 15.5. There will be a raised osmolar gap, but the anion gap will not increase until the intoxicated patient has had some time to process all that methanol into its acidic metabolites. Then, for a period of time the biochemistry results will reveal the classical picture with an increase in both anion and osmolar gaps. Finally, at some hypothetical point (where the patient is blind and comatose but not yet completely dead) the osmolar gap may decrease to a virtually normal level, leaving only a high anion gap.

References

Kraut, Jeffrey A., and Shelly Xiaolei Xing. "Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis." American Journal of Kidney Diseases 58.3 (2011): 480-484.

Question 7.3 - 2014, Paper 1

List two causes for the following combination of findings observed on a serum sample:

Parameter

Patient Value

Normal Adult Range

Measured osmolality

310 mOsm/L*

280 – 290

Sodium

125 mmol/L*

135 – 145

Potassium

4.0 mmol/L

3.5 – 5.0

Chloride

98 mmol/L

95 – 105

Bicarbonate

21 mmol/L*

22 – 32

Glucose

6.0 mmol/L

4.0 – 6.0

Urea

8.0 mmol/L

3.0 – 8.5

College Answer

Raised osmolar gap with normal AG
Mannitol
Glycine
Ethanol

Discussion

Let us dissect these results systematically.

  1. The A-a gradient cannot be calculated.
  2. There is no pH measurement; one assumes that there must be an acidaemia because the bicarbonate value is low.
  3. The PaCO2 is not available, and it is therefore impossible to assess respiratory compensation
  4. The SBE is not reported.
  5. The respiratory compensation is irrelevant (see point 3).
  6. The anion gap is  normal:
    (125) - (98  + 21) = 6, or 10 when calculated with potassium
  7. The osmolar gap is raised:
    Calculated osmolality is  (2×125) + (8 + 6) = 264 mOsm/L;
    whereas the measured osmolality is 310 mOsm/L, giving us a gap of 46 mOsm/L.

What could raise the osmolar gap but not  the anion gap? Well, any osmotically active agent which is not anionic, for instance any substance which fails to dissociate at physiologic pH. Counterintuitively, virtually all toxic alcohols fall into this category, as do various soluble sugars. A high anion gap acidosis does not develop until after you have managed t metabolise a large amount of toxic alcohol into some sort of organic acid.

Thus, the list of explanations includes the following:

  • Mannitol therapy
  • Glycine absorption (TURP syndrome)
  • Non-metabolised glycols: propylene glycol or polyethylene glycol (found in IV drug ampoules)
  • Maltose (IV immunoglobulin is suspended in maltose)
  • Ethanol
  • Soon (immediately) after toxic alcohol ingestion.

References

Kraut, Jeffrey A., and Shelly Xiaolei Xing. "Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis." American Journal of Kidney Diseases 58.3 (2011): 480-484.

Question 24 - 2014, Paper 1

a) Briefly explain the concept of the quantitative approach (Stewart's approach) to acid-base analysis.

b) How does the quantitative approach classify acid-base disturbances?

College Answer

a)
The quantitative approach to acid-base chemistry provides a mathematical explanation of the relevant variables that control H+ in body fluids and their interactions. The approach treats body fluids as a sys- tem that contains multiple interacting constituents.
The Henderson-Hasselbach approach to evaluating acid-base status considers the interactions of only a few variables in the system, such as pH, PCO2, and bicarbonate, whereas Stewart considers the interactions among more variables and allows one to identify the variables that control H+.
Quantitative approach uses physical laws of aqueous solutions to write equations that describe the interactions among the variables in the system. These laws are the maintenance of electrical neutrality, the satisfaction of the dissociation equilibria for weak electrolytes (partially dissociated when dissolved in water), and the conservation of mass.

An important basic concept of Stewart's principles is the classification of variables in a system as independent or dependent. Independent variables can be altered from outside the system without affecting each other. Dependent variables are thought of as internal to the system. Their values depend on the values of the independent variables and reflect the behaviour of the equilibrium reactions in the system.
Three independent parameters are known to control acidity in arterial or venous plasma. These parameters are the strong ion difference (SID), which summarises the strong or fully dissociated electrolytes, the total weak acid concentration (Atot), which summarises the non-volatile weak or partially dissociated electrolytes, and the partial pressure of carbon dioxide (PCO2). It is these 3 independent variables that control [H+].
Basic equation such as below should feature:
[SID] = [Na+] + [K+] + [Ca2+] + [Mg2+] - [CL-] - [Other Strong Anions/lactate].
[ATOT] = [PiTOT] + [PrTOT] + albumin.
b)
Classification of Primary Acid–Base Disturbances
Respiratory ↑ PCO2 ↓ PCO2
Non-Respiratory
a. Abnormal SID
i .Water excess/deficit ↓ SID, ↓ [Na+] ↑ SID, ↑ [Na+]
ii. Imbalance of strong anions
Chloride excess/ deficit ↓ SID, ↑ [Cl-] ↑ SID, ↓ [Cl-]
Unidentified anion excess ↓ SID, ↑ [XA-]
b. Non-volatile weak acids
i. Serum albumin ↑ [Alb] ↓ [Alb]
ii. Inorganic phosphate ↑ [Pi] ↓ [Pi]

Indicate essential points to achieve pass:

Clear description of the quantitative approach. This question is not intended to be answered at PhD biochemistry level but rather at a level that demonstrates a good consultant understanding of the issues e.g. if asked by a visiting team about quantitative acid-base.

Examiners' comments: Candidates were not expected to have an advanced knowledge of biochemistry but an overall understanding of the principles involved e.g. to allow an explanation of the issues to colleagues.

Discussion

A concept requiring a 504-page book to explain needs to be compacted into a 10-minute exam answer. The college has this editorial from 2004 on their site, titled "What exactly is the strong ion gap and does anybody care?"

In its briefest form:

  • The acid-base system is an interaction of several variables
  • There are independent variables, which can be altered from outside the system.
  • There are dependent variables which are altered by changes in the independent variables.
  • pH and HCO3- are dependent variables.
  • The independent variables are:
    • SID - the strong ion difference
    • ATOT - the total weak acid concentration
    • PaCO2
  • Thus, changes in any of the independent variables can cause a change in pH and HCO3-, i.e. acidosis and alkalosis.

Thus, acid-base disorders can be classified as:

  • Respiratory: increased or decreased PaCO2
  • SID changes:
    • due to excess or deficit of water
    • due to excess or deficit of strong ions
  • ATOT changes: excess or deficit of inorganic phosphate or albumin

Advantages of the Stewart method:

  • Quantitative mathematical explanation of acid-base disorders
  • A more scientific approach - applies the concepts of physical chemistry to traditional acid-base concepts
  • Accessible, logical framework for the design of resuscitation fluids

Disadvantages of the Steward method:

  • Complex
  • Substantially different to the well-validated classical approach; thus, produces confusion
  • Numerous variables, each measured with a small error, are combined- thus amplifying the measurement error
  • Fails to incorporate the buffering contribution of haemoglobin
  • No evidence that this approach has any influence on mortality

References

Morgan, T. J. "What exactly is the strong ion gap, and does anybody care?" Critical Care and Resuscitation (2004) 6: 155-166.

Sirker, A. A., et al. "Acid− base physiology: the ‘traditional’and the ‘modern’approaches."  Anaesthesia 57.4 (2002): 348-356.

Story, D. A., S. Poustie, and R. Bellomo. "Quantitative physical chemistry analysis of acid− base disorders in critically ill patients." Anaesthesia 56.6 (2001): 530-533.

Question 30.2 - 2014, Paper 1

A 35-year-old female with a history of poorly controlled hypertension presents with paraesthesia and weakness. Her blood results are shown below:

Parameter

Patient Value

Normal Adult Range

Sodium

145 mmol/L

135 – 145

Potassium

1.8 mmol/L*

3.5 – 5.0

Chloride

85 mmol/L*

95 – 105

Bicarbonate

40 mmol/L*

24 – 32

Urea

3.4 mmol/L

3.0 – 8.5

Creatinine

80 micromol/L

70 – 110

Parameter

Patient Value

Normal Adult Range

pH

7.56*

7.35 – 7.45

pO2

85 mmHg (11.3 kPa)

pCO2

46 mmHg* (6.1 kPa)*

35 – 45 mmHg (4.6 – 5.9 kPa)

Bicarbonate

40 mmol/L*

24 – 32

FiO2

0.21

a) Interpret these results.
 
b) List two likely diagnoses.
 
c) Give two drugs used to treat this condition.

College Answer

a)
Metabolic alkalosis with partial respiratory compensation and severe hypokalaemia.

b)
 Primary Hyperaldosteronism most likely secondary to an aldosterone producing adenoma (Conn's syndrome – 50 – 60%) or adrenal hyperplasia (40 – 50%).
 Licorice ingestion.
 Liddle's syndrome.
 Excessive diuretic use.

c)
 Aldosterone antagonist (spirinolactone or eplerenone).
 Amiloride.

Discussion

This question is identical to Question 18.2 from the first paper of 2011.

References

Question 12.3 - 2014, paper 2

The following arterial blood gas report was obtained from a 75-year-old female admitted to hospital with gastric outlet obstruction. She has had a rapid response team call for tachypnoea with a diagnosis of aspiration pneumonia.

Parameter Patient Value Normal Adult Range
FiO2 0.3  
pH 7.53* 7.35 – 7.45
PCO2 31 mmHg (4 kPa)* 35 – 45 (4.6 – 6.0)
PO2 83.7 mmHg (11 kPa)  
Bicarbonate 25 mmol/L 22 – 28
Standard Base Excess 3.3 mmol/L* -2.0 – +2.0

a) Comment on the acid-base status.
b) Give an explanation for these results.

College Answer

a)
Mixed respiratory and metabolic alkalosis

b)
Respiratory alkalosis from the hyperventilation due to the pneumonia
Metabolic alkalosis from vomiting (or diuretic use).

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high; ~91mmHg
  2. There is alkalaemia
  3. The PaCO2 is contributing
  4. The SBE is 3.3, suggesting a mild metabolic alkalosis
  5. The respiratory compensation is inadequate - the expected PaCO2 (25 × 0.7) + 20 = 37.5mmHg, and so there is also a respiratory alkalosis according to the Boston rules.
  6. The anion gap and delta ratio canot be calculated.

References

Question 23 - 2014, paper 2

A 72-year-old female, body mass index 17.5 kg/m2 , is admitted to the High Dependency Unit following a Medical Emergency Team call for tachypnoea and hypotension. She is known to have sepsis relating to a urinary tract infection and wound infection following extensive surgery for resection of a left thigh chondrosarcoma six weeks earlier.

Her biochemistry results are as follows:

Venous Sample
Parameter Patient Value Normal Adult Range
Sodium  139 mmol/L 134 – 146
Potassium  4.6 mmol/L 3.4 – 5.0
Bicarbonate  5.0 mmol/L* 22 – 32
Urea  11.2 mmol/L* 3.0 – 8.0
Creatinine 179 µmol/L* 45 – 90
Arterial Blood Gas
Parameter Patient Value Normal Adult Range
FiO2 0.3  
pH 7.18* 7.35 – 7.45
PCO2 14 mmHg (1.8 kPa) 35 – 45 (4.6 – 6.0)
PO2 104 mmHg (13.7 kPa)  
Bicarbonate 5.0 mmol/L* 22 – 28
Base Excess -22 mmol/L* -2.0 – +2.0
Sodium 141 mmol/L 134 – 146
Potassium 4.3 mmol/L 3.4 – 5.0
Chloride 114 mmol/L* 98 – 108
Glucose  6.9 mmol/L* 3.0 – 5.4
Lactate 1.0 mmol/L <1.5
Urinalysis
Parameter Patient Value
5-Oxoproline (Pyroglutamic acid)  > 3+ (16 mmol/mmol creatinine)
3-Hydroxybutyrate  1+
Acetoacetate 1+

a) Interpret her acid-base status.

With reference to her urinalysis:

b) Explain the significance.

c) List the likely predisposing factors in this patient.

d) Briefly outline the underlying pathophysiology.

e) List your management strategies.

College Answer

a)
Mixed high anion gap and normal anion gap metabolic acidosis with respiratory compensation
(AG = 22 and delta gap = 0.4 – 0.8)
[SIDA abbreviated = Na + K – Cl = 31.3 (decreased SID, raised Cl)]

b)
High levels of PGA imply that this is the cause of her underlying HAGMA
Low levels of ketones relate to relative starvation

c)
Predisposing factors in this patient are:
Elderly patient
Sepsis
Malnutrition
Renal impairment
May have had concomitant treatment with paracetamol and/or flucloxacillin
Liver function not given but liver dysfunction also predisposing factor
Congenital enzyme deficiencies unlikely

d)
Pathophysiology relates to glutathione depletion (sepsis, liver dysfunction, paracetamol via NAPQI) resulting in loss of negative feedback on synthesis of gamma-glutamylcysteine with subsequent increased production of pyroglutamic acid; or 5-oxoprolinase inhibition (flucoxacillin) resulting in decreased conversion of PGA to glutamate

e)
Management strategies
Supportive care and monitoring - oxygen, haemodynamic and renal support as indicated
Cease culprit drugs
Treat sepsis (appropriate antibiotics and surgical debridement)
Improve nutritional status
N-acetyl cysteine

Discussion

a)

Let us dissect these results systematically.

  1. The A-a gradient is high; ~92.4mmHg
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is -22, suggesting a severe metabolic acidosis
  5. The respiratory compensation is essentially complete - the expected PaCO2 (5 × 1.5) + 8 = 15.5mmHg, according to the Boston rules.
  6. The anion gap is (141) - (114 + 5) = 22, or 26.3 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (22 - 12) / (24 - 5) = 0.52
    Thus, there is both a HAGMA and a NAGMA here.

b)

The college rightly blames the high anion gap acidosis on pyroglutamic acid. The combined contribution from the ketones and lactate would not be enough to explain the anion gap.

c)

Pyroglutamic acidosis is discussed in greater detail elsewhere, and there is also a brief summary of this topic for revision. For a much deeper discussion, one can turn to Kortmann's 2008 article.

In brief, the predisposing factors to pyroglutamic acidosis in general are as follows:

Risk factors for depletion of glutathione

  • Paracetamol
  • Severe sepsis
  • Chronic alcoholism
  • Chronic liver failure of any cause
  • Weird diet, or malnutrition in general

Risk factors for dysfunction of 5-oxoprolinase

Risk factors for diminished 5-oxoproline clearance

  • Renal failure

The college also include old age as a risk factor.

d)

Specific management consists of addressing the synthesis and clearance of 5-oxoproline.

Thus:

  • Replenishing glutathione:
    • Adequate nutrition
    • N-acetylcysteine
    • Avoidance of paracetamol
    • Management of the sepsis
  • Increasing 5-oxoprolinase activity:
    • cessation of inhibitory drugs
  • Improving 5-oxoproline clearance
    • Fluid management of renal failure
    • Dialysis

References

Dempsey GA Lyall HJ, Corke CF, Scheinkestel CD. Pyroglutamic acidemia: a cause of high anion gap metabolic acidosis. Crit Care Med. 2000Jun;28(6):1803-7.

Duewall, Jennifer L., et al. "5-Oxoproline (pyroglutamic) acidosis associated with chronic acetaminophen use." Proceedings (Baylor University. Medical Center) 23.1 (2010): 19.

Akhilesh Kumar and Anand K. Bachhawat Pyroglutamic acid: throwing light on a lightly studied metabolite ,SPECIAL SECTION: CHEMISTRY AND BIOLOGY. CURRENT SCIENCE, VOL. 102, NO. 2, 25 JANUARY 2012. 288

Kortmann, W., et al. "5-Oxoproline as a cause of high anion gap metabolic acidosis: an uncommon cause with common risk factors." Neth J Med 66.8 (2008): 354-357.

Pitt, James J., and Simon Hauser. "Transient 5-oxoprolinuria and high anion gap metabolic acidosis: clinical and biochemical findings in eleven subjects." Clinical chemistry 44.7 (1998): 1497-1503.

 

Question 27 - 2014, paper 2

A 45-year-old previously healthy male was admitted to your ICU 5 days ago after a motor vehicle crash with chest and abdominal injuries. He is currently intubated and ventilated, is on FiO2 1.0 and positive end-expiratory pressure (PEEP) of 10 cmH2O. He is deeply sedated and on nor-adrenaline and adrenaline infusions at 10 μg/min each. He has become oliguric.

His blood biochemistry, haematology and arterial blood gases are as follows:

Venous Sample
Parameter Patient Value Normal Adult Range
Sodium  138 mmol/L 134 – 146
Potassium  7.1 mmol/L 3.4 – 5.0
Chloride  104 mmol/L 95 – 105
Urea  27 mmol/L* 3.0 – 8.0
Creatinine 260 µmol/L* 45 – 90
Haematology
Parameter Patient Value Normal Adult Range
Haemoglobin 120 g/L* 135 – 180
White blood cell 12.8 x 109 /L* 4.0 – 11.0
Platelets 42 x 109 /L* 140 – 400
Arterial Blood Gas
Parameter Patient Value Normal Adult Range
FiO2 1.0  
pH 7.01* 7.35 – 7.45
PCO2 45 mmHg (6 kPa) 35 – 45 (4.6 – 6.0)
PO2 70 mm Hg (9.3 kPa)  
Bicarbonate 11 mmol/L* 22 – 26
Base Excess -19 mmol/L* -2.0 – +2.0
Glucose  7.5 mmol/L* 4.0 – 6.0
Lactate 13 mmol/L* < 2.0

a) Summarise the findings of the blood tests.

b) What ae the likely underlying causes of the lactic acidosis?

c) Outline your immediate management priorities at this point.

College Answer

a)
High anion gap metabolic acidosis (with apparent normal SID). Note AG 33 which is NOT adequately
explained just by a lactate of 13 mmol
Inadequate or inappropriate respiratory compensation
Hypoxaemia (P/F ratio 70)
Acute renal failure (note urea:creatinine ratio).
Hyperkalaemia

b)
Sepsis with shock
Ongoing hypovolaemia
Hypoperfusion eg septic cardiomyopathy; abdominal compartment syndrome
Possible gut ischemia
Perhaps adrenaline (also seen with other catecholamines – unpredictable)

c)
Optimise ventilation.
Exclude pneumothorax.
Probably needs more PEEP after some volume.
Minimise airway pressures, limit tidal volume, tolerate hypercarbia (though concerned about pH < 7!!!)

Optimise cardiovascular function.
Urgent echocardiogram.
Volume replacement if possible.
Measure continuous cardiac output (PiCCO or PAC).
Measure SvO2 or ScvO2.
Exclude abdominal compartment syndrome
Rationalise inotropes. Stop adrenaline, use noradrenaline as required

Emergency management of hyperkalaemia with calcium, bicarbonate, insulin, dextrose and then haemodialysis!
Urgent CRRT – for both potassium and acidosis use of hemosol buffer

Broad-spectrum IV antibiotics (rational answer required)

Discussion

a)

Let us dissect these results systematically.

  1. The A-a gradient is high; ~586.8mmHg. The P/F ratio is 70.
  2. There is acidaemia
  3. The PaCO2 is not compensating for the acidaemia
  4. The SBE is -19, suggesting a severe metabolic acidosis
  5. The respiratory compensation is essentially non-existent - the expected PaCO2 (11 × 1.5) + 8 = 21mmHg, according to the Boston rules. Thus, there is also a respiratory acidosis.
  6. The anion gap is (138) - (104 + 11) = 23, or 30.1 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (23 - 12) / (24 - 11) = 0.84 Thus, this is an almost pure HAGMA, with some minor contribution from the normal anion gap acidosis.

The college seem to have used some sort of weird anion gap formula. Usually they omit potassium from the calculations, but if you did not include potassium, the anion gap would be 23. What mysterious cation did the college include? Who can say. There must have been either 2.9 or 10mmol/L of it, whatever it was. Anyway, it does not change the interpretation in this case, but it does demonstrate some of the shortcomings of the anion gap as a diagnostic tool.

b) The causes of lactic acidosis are discussed at great length elsewhere.

In brief, here is the familiar table of Cohen-Woods aetiologies, with the causes most relevant to this case highlighted in bold script:

Causes of Lactic Acidosis

Type A lactic acidosis: impaired tissue oxygenation 

  • Shock: circulatory collapse
  • Regional ischaemia (eg. the gut)
  • Severe hypoxia
  • Severe anaemia
  • Carbon monoxide poisoning

Type B1 lactic acidosis, due to a disease state

  • Malignancy
  • Thiamine deficiency
  • Ketoacidosis /HONK
  • Septic shock
  • Impaired hepatic or renal clearance

Type B2 drug-induced lactic acidosis

  • Beta-2 adrenoceptor agonists
  • Metformin
  • Isoniazid
  • Cyanide (and by extension nitroprusside)
  • Xylitol, sorbitol, fructose
  • Propofol
  • The toxic alcohols eg. methanol
  • Paracetamol
  • Salicylates
  • NRTIs (nucleoside reverse transcriptase inhibitors)

Type B3 : inborn errors of metabolism

  • Numerous possible defects:
    • Pyruvate dehydrogenase deficiency
    • Electron transport chain enzyme defects
    • G6PD

c)

The management priorities presented by the college are difficult to improve upon, short of pruning away some of the excess exclamation marks. It does not vary greatly from the many other "manage your way out of this multiorgan system failure" questions. The specific feature which the college wanted us to focus on seems to have been the hyperkalemia; any management strategy which failed to address it would probably have been viewed as irresponsible.

References

Question 3.1 - 2015, Paper 1

The following data are from the arterial blood gas analysis of a 71-year-old male with necrotising fasciitis:

Parameter Patient Value Normal Adult Range
Barometric pressure 760 mmHg (100 kPa) .
FiO2 0.3 .
pH 7.43 7.35 – 7.45
PCO2 23 mmHg (3.1 kPa)* 35 – 45 (4.6 – 5.9)
PO2 107 mmHg (14.3 kPa) .
Bicarbonate 15 mmol/L* 22 – 26
Standard Base Excess -8.6 mmol/L* -2.0 – +2.0
Lactate 23.0 mmol/L* 0.2 – 2.5
Sodium 147 mmol/L* 137 – 145
Potassium 6.7 mmol/L* 3.2 – 4.5
Chloride 95 mmol/L* 100 – 110

List the acid-base abnormalities. (30% marks)

College Answer

Lactic acidosis
Anion gap elevation (37 mEq/L)
Metabolic alkalosis
Respiratory alkalosis

Discussion

This is a triple disorder.

Let us dissect these results systematically.

  1. The A-a gradient is high; ~78mmHg
  2. There is neither alkalaemia nor acidaemia
  3. The PaCO2 is low, which is a move in the appropriate direction given the metabolic acidosis
  4. The SBE is -8.6, suggesting a metabolic acidosis
  5. The respiratory compensation is excessive - the expected PaCO2 (15 × 1.5) + 8 = 30.5mmHg, and so there is also a respiratory alkalosis according to the Boston rules.
    According to the Copenhagen rules, the the expected PaCO2 = (40 - SBE) = 31.4mmHg.
    So, in this case there is no Trans-Atlantic disagreement.
  6. The anion gap is (147) - (95  + 15) = 37, or 43.7 when calculated with potassium.
  7. The delta ratio (assuming an albumin of 40) would therefore be (37 - 12) / (24 - 15) = 2.77 thus there is a high anion gap metabolic acidosis which co-exists with a metabolic alkalosis.
    Note that without taking this step, the candidates would still have guessed that there is an underlying metabolic alkalosis. How else would you have a normal pH with a lactate of 23?
 

References

Question 3.2 - 2015, Paper 1

Inspect the following biochemical data:

Parameter Patient Value Normal Adult Range
Sodium 145 mmol/L 135 – 145
Potassium 4.0 mmol/L 3.2 – 4.5
Chloride 101 mmol/L 100 – 110
Bicarbonate 34 mmol/L* 22 – 26
pH 7.20* 7.35 – 7.45
pCO2 90 mmHg* (11.7 kPa)* 35 – 45 (4.6 – 5.9)

Describe the abnormalities and give an example of an associated clinical scenario. (20% marks)

College Answer

Acute respiratory acidosis with metabolic alkalosis
Clinical scenario – acute respiratory failure in COAD (Acute on chronic respiratory failure)

Discussion

Let us dissect these results systematically.

  1. Oxygenation cannot be assessed
  2. There is acidaemia
  3. The PaCO2 is high, and looks to be the cause of the acidosis
  4. The SBE is not available, but the bicarbonate is high, suggesting a metabolic alkalosis
  5. The increase in bicarbonate is excessive compared with the increase expected from the hypercapnia on its own: the expected HCO3 = (5 × 1) + 24 = 29 mmol/L, and so there is also a metabolic alkalosis according to the Boston rules. The Copenhagen rules cannot be applied in this case, as they require an SBE.
  6. The anion gap is (145) - (101 + 34) = 10, or 14 when calculated with potassiu, i.e. totally normal.
  7. The delta ratio is therefore irrelevant.
 

References

Question 3.3 - 2015, Paper 1

The following data are taken from a 74-year-old female who has just been admitted to ICU following surgery for revision of an infected hip prosthesis.

Parameter Patient Value Normal Adult Range
Sodium 147 mmol/L* 135 – 145
Potassium 3.6 mmol/L 3.2 – 4.5
Chloride 124 mmol/L* 100 – 110
Haemoglobin 106 g/L* 115 – 155
FiO2 0.3 .
pH 7.32* 7.35 – 7.45
PCO2 32 mmHg (4.3 kPa)* 35 – 45 (4.6 – 5.9)
PO2 63 mmHg (8.4 kPa) .
Bicarbonate 16.0 mmol/L* 22.0 – 26.0
Standard Base Excess -9.0 mmol/L* -2.0 – +2.0

a)  Describe the acid-base abnormalities.(20% marks)

b)  What is the likely cause of this disturbance? (20% marks)

c)  What is the underlying biochemical mechanism?(10% marks)

College Answer

a)
Normal anion gap metabolic acidosis with appropriate respiratory compensation.

b)
Resuscitation with large volume saline infusion.

c)
ECF dilution by fluid with strong ion difference of zero (or any reasonable explanation.)

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is increased (if the atmospheric pressure is 760mmHg, the gradient is  110, with a P/F ratio of 210)
  2. There is acidaemia
  3. The PaCO2 is low, which is appropriate in acidaemia
  4. The SBE is -9.0, suggesting a metabolic acidosis
  5. The respiratory compensation is appropriate: the expected PaCO2 = (16 × 1.5) + 8 = 32 mmHg (according to the Boston rules) The Copenhagen rules agree: the expected PaCO= (40 - SBE) = 31mmHg.
  6. The anion gap is normal: (147) - (124 + 16) = 7, or 10.6 when calculated with potassium
  7. The delta ratio is therefore irrelevant.

It is pleasing to see the use of  Stewart's physicochemical approach to acid-base analysis in the college answer.

 

References

Question 3.3 - 2015, Paper 2

You are asked to review a 44-year-old male known epileptic following a prolonged generalised tonic-clonic convulsion. He is intubated and ventilated.
The arterial blood gas analysis is as follows:

Parameter Patient value Normal adult range
FiO2 0.5  
pH 7.15* 7.35–7.45
pCO2 35 mmHg (4.6 kPa) 35-45 (4.6-6)
pO2 105 mmHg (14 kPa) 75-98 (10-13)
HCO3- 10.3 mmol/L 22.0-26.0

List the abnormalities on the blood gas and give the most likely cause of each abnormality.
(30% marks)

College Answer

Metabolic acidosis – lactic acidosis secondary to prolonged seizures
Respiratory acidosis (or inadequate compensation) – central hypoventilation or Inadequate mechanical ventilation
Increased A-a gradient - aspiration pneumonia

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high:
    The alveolar oxygen tension is (0.5 × 713) - (35 × 1.25) = 312 mmHg;
    thus the A-a gradient is around 208 mmHg.
  2. There is acidaemia
  3. The PaCO2 is low-normal, which is a move in the appropriate direction given that there is acidaemia.
  4. The SBE is not offered, but there is a low bicarbonate which suggests a metabolic acidosis.
  5. The respiratory compensation is inadequate - the expected PaCO2 (10.5 × 1.5) + 8 = 23.8 mmHg, and so there is also a respiratory acidosis according to the Boston rules. There is no base excess measurement, and thus the Copenhagen rules cannot be used.
  6. The anion gap or delta ratio cannot be calculated.

Thus, there is:

  • Hypoxia (widened A-a gradient)
  • Respiratory acidosis
  • Metabolic acidosis

The college expected their candidates to make an intuitive leap, and to assume that the history of prolonged seizure is enough to explain the acidosis (because lactate) and the hypoxia (because aspiration).

References

Question 20.1 - 2015, Paper 2

A 50-year-old male with a history of chronic pancreatitis presents with several days of nausea and vomiting. His biochemistry profile is as follows:

Parameter

Patient Value

Normal Adult Range

Arterial Blood Gas

FiO2

0.4

pH

7.62*

7.35 – 7.45

PCO2

62 mmHg* (8.2 kPa)*

36

– 45 (4.6 – 6.0)

PO2

133 mmHg (17.5 kPa)

Bicarbonate

65 mmol/L*

21

– 28

Base Excess

> 30 mmol/L*

-3 – +3

Sodium

149 mmol/L*

135 – 145

Potassium

3.3 mmol/L*

3.5 – 5.2

Chloride

53 mmol/L*

95

– 110

Calcium ionised

0.74 mmol/L*

1.12 – 1.32

Lactate

2.7 mmol/L*

< 1.3

Venous biochemistry

Urea

34.9 mmol/L*

3.0 – 8.0

Creatinine

431 micromol/L*

60

– 110

Interpret the abnormalities in the above results and give likely underlying causes.                             (30% marks)

College Answer

Severe metabolic alkalosis (raised SID)
Respiratory compensation (incomplete)

High anion gap (approx. 31) metabolic acidosis
Profound hypochloraemia

Gastric losses and fluid depletion causing chloride loss and metabolic alkalosis

Metabolic acidosis secondary to renal failure (acute? Acute on chronic?) +/- sepsis from pancreatitis and/or gastro-enteritis
CO2 retention as compensation for severe metabolic alkalosis

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high:
    The alveolar oxygen tension is (0.4 × 713) - (62 × 1.25) = 207.7;
    thus the A-a gradient is 74.7.
  2. There is alkalaemia.
  3. The PaCO2 is high, which is a move in the appropriate direction given the degree of alkalaemia.
  4. The SBE is  over 30 mmol/L, suggesting a severe metabolic alkalosis.
    If the SBE was not available, the bicarbonate of 65 would have been impressive enough.
  5. The respiratory compensation is adequate. Only to the Boston rules apply, as the precise value of SBE is not given.
    The expected PaCO2 (65 × 0.7) + 20 = 65.5mmHg, and so there is totally appropriate respiratory compensation.
  6. The anion gap is raised: (149) - (53  + 65) = 31, or 34.3 when calculated with potassium.
  7. The delta ratio cannot be calculated, as there is a metabolic alkalosis instead of a metabolic acidosis here.

So, in summary, the blood abnormalities are:

  • Hypoxia
  • Alkalaemia
  • Metabolic alkalosis with hypochloraemia
  • Hypernatremia
  • Hyperlactataemia
  • A high anion gap, which is not completely accounted for by the raised lactate, and which could represent ketones or non-volatile acids associated with renal failure.
  • Ionised hypocalcemia
  • Renal failure (impossible to say, acute or chronic)

The college make a few strange statements here. For instance, the respiratory compensataion for this metabolic alkalosis is complete, but they think it is not. Are we using the same Boston equations? If we were to use the Copenhagen rules instead, we would expect the PaCO2 to be 40 + (30 ×0.6) = 58mmHg, and that would still be withing 4mmHg of the measured value.

So, it is difficult to tell exactly why the college think the compensation is incomplete. Certainly, complete compensation does not mean the normalisation of pH has been achieved.

In 1984, in his educational article for Kidney International  John Harrington explored this issue, and concluded that the relationship between PaCO2 and HCO3- remains stable and near-linear for a broad range of values, extending even into the ridiculous.  Every 1mmol/L rise in bicarbonate was matched by a 0.7mmHg increase in PaCO2. in a series of cruel human experiments on alkalotic volunteers who were either fed bicarbonate and THAM for many days  by Goldring et al (1962), or had acetate administered via dialysis circuits by De Strihou et al (1973). If one plugs this rate of rise into an online calculator, one observes a rise of pH by about 0.01 for ever 1mmol increase in bicarbonate.

So, the pH will inevitably trend to alkalaemia. Furthermore, it is possible to demonstrate that the correction of pH back to 7.45 would require a PaCO2 of around 94mmHg, and this cannot be viewed as a physiologically beneficial move by any sane person. For this very sensible reason, respiratory compensation for truly severe metabolic alkalosis could never take place outside of mathematical models. To achieve a stable PaCO2 of 94mmHg the alkalotic person would have to be severely hypoxic on room air (with an alveolar oxygen tension no greater than 34 mmHg), and breathing at a rate of around 2 breaths per minute.

References

Goldring, Roberta M., et al. "Respiratory adjustment to chronic metabolic alkalosis in man." Journal of Clinical Investigation 47.1 (1968): 188.

De Strihou, C. Van Ypersele, and A. Frans. "The respiratory response to chronic metabolic alkalosis and acidosis in disease." Clinical Science 45.4 (1973): 439-448.

Harrington, John T. "Metabolic alkalosis." Kidney international 26.1 (1984): 88-97.

Question 20.2 - 2015, Paper 2

A 28-year-old previously fit male presents with a two-day history of fever, headache and a widespread rash.

Results of investigations are as follows:

Parameter

Patient Value

Normal Adult Range

FiO2

0.3

pH

6.99*

7.35 – 7.45

PCO2

26* mmHg (3.4 kPa)*

35

– 45 (4.6 – 6.0)

PO2

78 mmHg (10.3 kPa)

SpO2

96%

95

– 100

Base Excess

-27.5 mmol/L*

-3.0 – +3.0

Bicarbonate

6 mmol/L*

22

– 27

Sodium

126 mmol/L*

135 – 145

Potassium

5.1 mmol/L*

3.5 – 4.5

Creatinine

186 micromol/L*

60

– 110

Glucose

2.4 mmol/L*

3.6 – 7.7

Lactate

16.0 mmol/L*

0.2 – 2.0


Blood cultures show Gram-negative cocci.

a)    List the abnormalities shown by the ABG.    (10% marks)

b)    Give the most likely diagnosis.    (5% marks)

c)    What complication of this condition may have occurred?    (5% marks)

College Answer

a)

Severe lactic acidosis with inadequate respiratory compensation and acute renal impairment and hypoglycaemia.

b)
Meningococcal septicaemia

c)
Waterhouse Friderichsen syndrome.

Multi-organ failure with liver and renal dysfunction is a reasonable answer and was given some credit.

Discussion

a) Let us dissect the results systematically:

  1. The A-a gradient is high:
    The alveolar oxygen tension is (0.3 × 713) - (26 × 1.25) =
    Thus, the A-a gradient is 103.4.
  2. There is acidaemia.
  3. The PaCO2 is low, which is a move in the appropriate direction given the metabolic acidosis
  4. The SBE is -27.5, suggesting a severe metabolic acidosis.
  5. The respiratory compensation is insufficient.
    According to the Boston rules the expected PaCO2 is (6 × 1.5) + 8 = 17mmHg, and so there is also a respiratory acidosis.
    According to the Copenhagen rules, the the expected PaCO2 = (40 - SBE) = 12.5mmHg, which is an unrealistic number and which demonstrates the breakdown of these rule sets in the setting of truly extreme situations.
  6. The anion gap cannot be calculated, because no chloride is offered. One can only expect that it is  high, given the extremely low bicarbonate value and the extremely high lactate.

Thus, in summary:

  • Severe acidaemia
  • Severe lactic acidosis
  • Inadequate respiratory compensation (thus, respiratory acidosis)
  • Widened A-a gradient
  • Hyponatremia and mild hypokalemia
  • Renal failure (impossible to say whether acute or chronic)
  • Hypoglycaemia
  • gram negative cocci in the blood (and that could only be a few different things: namely, Moraxella or Neisseria among the aerobes, and Veilonella among the anaerobes)

b)

The trainees were expected to identify the meningococcaemia on the basis of "fever, headache and a widespread rash". This is probably somewhat unfair. The college, in recognition of this fact, acknowledged as correct any answer which explained the lactic acidosis by blaming it on sepsis-induced liver failure.

c)

The patient has features of hypoadrenalism, consistent with Waterhouse-Friedrichsen syndrome. If the trainee managed to connect the dots (gram negative cocci, low sodium, high potassium) they would have only earned a paltry 5% of the total marks for Question 20, which is a poor marks to effort ratio.

References

Rosenstein, Nancy E., et al. "Meningococcal disease." New England Journal of Medicine 344.18 (2001): 1378-1388.

Mautner, L. S., and W. Prokopec. "Waterhouse-Friderichsen Syndrome."Canadian Medical Association journal 69.2 (1953): 156.

Ferguson, J. Howard, and Orren D. Chapman. "Fulminating meningococcic infections and the so-called Waterhouse-Friderichsen syndrome." The American journal of pathology 24.4 (1948): 763.

Question 20.3 - 2015, Paper 2

The following arterial blood gas result was obtained from a 65-year-old lady with exacerbation of chronic obstructive pulmonary disease (COPD), day 7 in ICU following intubation and ventilation for respiratory failure.

Parameter

Patient Value

Normal Adult Range

FiO2

0.3

pH

7.48*

7.35

– 7.45

PCO2

42 mmHg (5.5 kPa)

35

45 (4.6 – 6.0)

PO2

104 mmHg (13.7 kPa)

Total haemoglobin

122 g/L

115 – 165

SpO2

98%

95

100

Base Excess

7.0 mmol/L*

-3.0 – +3.0

Bicarbonate

31 mmol/L

22

32

a)    Interpret the arterial blood gas.    (10% marks)

b)    Give four possible reasons for the acid-base disturbance seen.    (10% marks)

College Answer

a)

Metabolic alkalosis

Raised A-a gradient

b)

Diuretics

Steroids

NG losses

Post hypercapnia

Discussion

A systematic approach to this problem would resemble the following:

  1. The A-a gradient is high:
    The alveolar oxygen tension is (0.3 × 713) - (42 × 1.25) = 161.4
    thus the A-a gradient is 57.4
  2. There is alkalaemia.
  3. The PaCO2 is on the high end of normal, which is a move in the appropriate direction given the presence of alkalaemia
  4. The SBE is 7.0 mmol/L, suggesting a mild metabolic alkalosis
    If the SBE was not available, the bicarbonate of 31 would have been enough to call this a metabolic alkalosis
  5. The respiratory compensation is adequate.
    According to the Boston rules, the expected PaCO2 is (31 × 0.7) + 20 = 41.7mmHg, and so there is totally appropriate respiratory compensation.
    With the Copenhagen rules, we can expect a PaCO2 of 44.2mmHg, which is close enough.
  6. The anion gap cannot be calculated, and it is in any case irrelevant.

In summary:

  • Raised A-a gradient
  • Metabolic alkalosis

Why would this be? One may refer to the list of causes for metabolic alkalosis. In a ventilated COPD patient with a normal-looking PaCO2 one could very easily point the blame at a posthypercapneic state.In fact, that is the only thing you can conclude from the bare minimum history the college has given. However, the question asks for four possible reasons. The college model answer offers diuretics, steroids and NG losses as potential contributors. Because of how little history is given, rhese differentials are at least as likely as the use of β-lactam antibiotics, Liddle's syndrome or clay ingestion.

References

Banga, Amit, and G. C. Khilnani. "Post-hypercapnic alkalosis is associated with ventilator dependence and increased ICU stay." COPD: Journal of Chronic Obstructive Pulmonary Disease 6.6 (2009): 437-440.

Question 23.1 - 2015, Paper 2

A 70-year-old male presents to the ED with a 2-week history of increasing dyspnoea, cough with altered sputum and fever. Past history includes chronic obstructive airways disease (COPD), lung cancer seven years ago treated with chemotherapy and radiation therapy with no sign of recurrence since.

Examination findings included RR 30 breaths/min, BP 110/70mmHg, HR 145 bpm, Temp 37.4ºC, anxious and distress but tired and peripherally cold and cyanosed.

CXR shows findings consistent with COPD and right lower lobe infiltrate.

The following arterial blood gas is taken one hour after receiving 2 litres of fluid resuscitation, antibiotics and bi-level non-invasive ventilation (NIV), at FiO2 = 1.0.

Parameter

Patient Value

Normal Adult Range

FiO2

1.0

pH

7.16*

7.35

– 7.45

PCO2

33 mmHg* (4.3 kPa)*

35

45 (4.6 – 6.0)

PO2

272 mmHg (38.5 kPa)

Bicarbonate

11 mmol/L*

22

30

Base Excess

-17 mmol/L*

-3 – +3

Sodium

138 mmol/L

135 – 145

Potassium

4.3 mmol/L

3.5 – 5.0

Chloride

121 mmol/L*

95

110

Glucose

13.1 mmol/L*

3.5 – 7.8

Lactate

6.4 mmol/L*

0.6 – 2.4

Haemoglobin

131 g/L*

135 – 175

Creatinine

150 micromol/L*

70

120

a)  Give your interpretation of the arterial blood gas and outline potential causes. 

(40% marks)

College Answer

a)
ABG:

Metabolic acidosis, normal anion gap however mixed cause (hyperchloremic predominant), high lactate and renal impairment.

Respiratory compensation but less than expected (superimposed respiratory acidosis). Impaired oxygenation with moderate shunt PaO2:FiO2 272 – A-a DO2 400.
Hyperglycemia (stress response).

Dx.

Type 1 respiratory impairment secondary to pneumonia on background of COAD.
Inadequate respiratory compensation due to fatigue and reduced respiratory reserve (COAD).
Metabolic acidosis due to:

  • Chloride excess - fluid resuscitation
  • Lactate elevation – sepsis plus inadequate cardiac output.
  • Renal impairment

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high:
    The alveolar oxygen tension is (1.0 × 713) - (33 × 1.25) = 671.75mmHg
    Thus, the A-a gradient is 399.75.
    This would be consistent with a large shunt, though as has been discussed elsewhere, A-a gradient is an oxygen tension-based measure and therefore cannot be used to make the diagnosis of shunt (only to discriminate hypoventilation from all other causes of hypoxia). With the history of
  2. There is acidaemia.
  3. The PaCO2 is low, which is a move in the appropriate direction given the degree of acidaemia
  4. The SBE is -17, suggesting a metabolic acidosis.
  5. The respiratory compensation is inadequate, whichever side of the Atlantic debate you're on.
    The expected PaCO2 (11 × 1.5) + 8 = 24.5mmHg, and so there is also a respiratory acidosis according to the Boston rules.
    According to the Copenhagen rules, the the expected PaCO2 = (40 - SBE) = 23mmHg.
  6. The anion gap is (138) - (121 + 11) = 6, or 10.3 when calculated with potassium.
    Later in this same SAQ we get the albumin level (in Question 23.2) and it is 27g/L. The expected anion gap is therefore 8.75. Thus, this is a pure normal anion gap metabolic acidosis, with barely any contribution from the lactate.

In summary:

  • Widened A-a gradient
  • Normal anion gap metabolic acidosis, with minimal respiratory compensation (thus, also a respiratory acidosis).
  • Hyperlactataemia
  • Hyperglycaemia
  • Renal impairment

References

Question 3.2 - 2015, Paper 2

The following data were obtained from a patient who had been observed overnight in the Emergency Department with minor fractures. The patient is otherwise well and currently asymptomatic.

Venous Biochemistry

Parameter

Patient Value

Normal Adult Range

Sodium

131 mmol/L*

135 – 145

Potassium

>10 mmol/L*

3.5 – 4.5

Chloride

98 mmol/L

95

105

Bicarbonate

14 mmol/L*

22

26

Glucose

1.2 mmol/L*

3.5-6.1

Creatinine

70 μmol/L

70

120

Lactate dehydrogenase (LDH)

600 U/L*

60

100

Phosphate

2.10 mmol/L*

0.65

– 1.45

Lactate

4.3 mmol/L*

< 2.0

Give the most likely cause for the above biochemical abnormalities?

Justify your answer.    (40% marks)

College Answer

Artefact; – This blood sample was left longer than 6 hours before it was processed for above investigations. (Note to examiners - This is not just a haemolysed sample – haemolysis alone does not cause hypoglycaemia and lactic acidosis, though it will cause other abnormalities).

1)    Potassium, phosphate and LD enter the serum from red cell due to haemolysis and Na/K pump dysfunction.

2)    Low Na – shift into red cell in exchange for potassium.

3)    RBCs consume glucose and generate lactate.

Discussion

An ideal reference for this answer is a 2008 paper by Tanner et al, examining the delayed processing of samples collected in rural and remote areas. The studies have discovered that over 24 hours of stoarge various changes take place. These changes (and the reasons behind them) were as follows:

Escape of cellular contents due to haemolysis

  • Potassium increases. After 24 hours, Tanner et al found the original K+ level of 3.8 increased to 8.0.
  • Phosphate increases. In the same study, the PO4- went from an average value of 1.36 to 4.36.
  • Total protein increases
  • LDH increases

Compartment shift

  • Sodium decreases

Metabolism by live cells

  • Acidosis develops
  • LDH increases (also because of anaerobic metabolism)
  • Glucose decreases (consumed by RBCs)
  • Lactate increases (produced by RBCs)
  • PaO2 decreases and PaCO2 increases as a consequence of RBC metabolism (in the experiments by Biswas et al (1982), the PaO2 fell by up to 40% in samples which were stored at room temperature for twenty minutes. This ameliorated by storing the sample at 4°C, but all sorts of other problems develop as a consequence of this).

References

Baird, Geoffrey. "Preanalytical considerations in blood gas analysis." Biochemia medica 23.1 (2013): 19-27.

Biswas, C. K., et al. "Blood gas analysis: effect of air bubbles in syringe and delay in estimation." Br Med J (Clin Res Ed) 284.6320 (1982): 923-927.

Woolley, Andrew, and Keith Hickling. "Errors in measuring blood gases in the intensive care unit: effect of delay in estimation." Journal of critical care 18.1 (2003): 31-37.

Hankinson, S. E., et al. "Effect of transport conditions on the stability of biochemical markers in blood." Clinical Chemistry 35.12 (1989): 2313-2316.

Tanner, Melissa, et al. "Stability of common biochemical analytes in serum gel tubes subjected to various storage temperatures and times pre-centrifugation." Annals of Clinical Biochemistry 45.4 (2008): 375-379.

Question 4.1 - 2016, Paper 1

A previously fit and well 41 -year-old male underwent an anterior resection under general anaesthesia with regional blockade. In recovery he required additional analgesia for escalating pain and treatment for nausea, following which he had an apparent seizure.

The following arterial blood gas sample was taken during resuscitation:

Parameter

Patient Value

Normal Adult Range

FiO2

0.6

6.91*

7.35 - 7.45

PCO2

64 mmH 8.5 kPa *

35 —45 (4.6 —6.0

PO2

158 mmH 21 kPa *

75-98 (10- 13)

SaO2

96%

Bicarbonate

12 mmol/L*

22 - 26

Base Excess

-18 mmol/L*

Sodium

145 mmol/L

135 - 145

Potassium

4.1 mmol/L

3.5 - 5.2

Chloride

110 mmol/L

95- 110

Lactate

16 mmol/L*

Haemoglobin

166 g/L*

115- 160

Glucose

9.0 mmol/L*

3.6 - 7.7

Describe the acid-base abnormality. (20% marks)

Give six possible causes for this clinical and biochemical scenario. (30% marks)

College Answer

a)  

  • Severe acidaemia due to a mixed metabolic (high anion gap lactic acidosis) and respiratory acidosis. Anion Gap is 27.

b)                                        

  • Dystonic drug reaction
  • Intra-abdominal catastrophe
  • Acute Intracranial event e.g. SAH
  • Local Anaesthetic toxicity
  • Myocardial infarction
  • Anaphylaxis 
  • Seizure

Discussion

a)

Let us dissect these results systematically.

  1. The A-a gradient is high; ~347.8 mmHg.
    (713 × 0.6) - (64 × 1.25)
    The P/F ratio is 263.
  2. There is acidaemia
  3. The PaCO2 is not compensating for the acidaemia
  4. The SBE is -18, suggesting a severe metabolic acidosis
  5. The respiratory compensation is essentially non-existent - the expected PaCO2 (12 × 1.5) + 8 = 26mmHg, according to the Boston rules. Thus, there is also a respiratory acidosis.
    (Copenhagen rules can also be applied, and yield an expected PaCO2 of 22 mmHg)
  6. The anion gap is raised:  (145) - (110 + 12) = 23, or 27.1 when calculated with potassium (note that this is one of those few SAQs where the college examiners included the potassium value in their anion gap calculation).
    The delta ratio, usinng potassiumless values and assuming a normal anion gap is 12 and a normal bicarbonate is 24, would  be (23 - 12) / (24 - 12) = 0.91

Thus, this is an almost completely pure HAGMA and a respiratory acidosis.

b) The key features of history are abdominal surgery, worsening pain,  analgesia, and antiemetics. Then, the patient had an "apparent seizure". The college wanted explanations of this "clinical and biochemical" picture. The following differentials were constructed without the benefit of the college model answer, before the official paper was released, and they differ from the college answer. The college had the LA toxicity, but they also threw in a dystonic drug reaction, intra-abdominal catastrophe, myocardial infarction, anaphylaxis and subarachnoid haemorrhage. It is unclear whether the differentials offered below would have scored any marks.

  1. Sepsis: the lactic acidosis is due to sepsis, and the "seizure" was rigors.
  2. Hypovolemic shock due to third space losses: the haemoglobin is raised, suggesting that there has been haemoconcentration. Either there are ongoing  third space losses, or the anaesthetist was insufficiently generous with the IV fluids. Lactate is explained by the shock state.
  3. Epilepsy: the patient is an epileptic and the combination of abdominal sepsis and opiates lowered his seizure threshold
  4. Local anaesthetic toxicity: the patient had a seizure because some of the local anaesthetic from the regional blockade was inadvertantly administered intravenously (hence the worsening pain: the block was of poor quality)
  5. Obstructive sleep apnoea: the patient is polycythaemic, and may have long-standing OSA- this, in combination with the opiates he received, caused the respiratory failure component. Hypercapnea then caused a seizure.
  6. Neuroleptic malignant syndrome: the patient got some "analgesia" which might have been opiates or tramadol, and this might have interacted with his usual SSRIs. And then he got some metoclopramide or prochlorperazine, causing a seizure.

Generic causes of a lactic acidosis are also offered below, for completeness

References

Question 4.2 - 2016, Paper 1

The following venous blood results are from a 52-year-old female who has had a prolonged ICU course following extensive surgery for resection of a pelvic sarcoma, complicated by sepsis and multi-organ dysfunction.

Venous Blood Gas

Parameter

Patient Value

Normal Adult Ran e

7.06*

7.32 - 7.43

PC02

42 mmH (5.5 kPa)

27 - 50 (3.5 -6.6)

P02

44 mmH (5.8 kPa)

36 —44 (4.7 — 5.8)

Bicarbonate

11 mmol/L*

22 - 38

Base Excess

-18 mmol/L*

02 Saturation

70 - 80

Sodium

140 mmol/L

135 - 145

Potassium

3.8 mmol/L

3.5 - 5.2

Chloride

119 mmol/L*

95 - 110

Anion Gap

14 mmol/L

7 - 17

Calcium Ionised

1.30 mmol/L

1 .12 - 1 .32

Glucose

10.6 mmol/L*

3.0 — 5.4

Lactate

1.0 mmot/L

< 1.5

Haemo lobin

116

IL

115 - 160

Urea

9.3 mmol/L*

3.0 - 8.0

Creatinine

244 mol/L*

45 - 90

a) Describe the acid-base disturbance in the above results           (10% marks)

b) Give possible explanations. (20% marks)

College Answer

 a)                                     

  • Hyperchloraemic metabolic acidosis (normal/non-anion gap) with respiratory acidosis (no respiratory compensation acceptable)

 b)                                                                                                    

  • Renal tubular acidosis (probably Type 1) secondary to nephrotoxicity (sepsis, drugs, obstruction)
  • GI losses (complicated abdomino-pelvic surgery)
  • Resuscitation with hyperchloraemic fluids
  • Respiratory depression secondary to opiates (or any reasonable explanation)

Discussion

a)

Let us dissect these results systematically.

  1. The A-a gradient cannot be estimated, as the gas is venous.
  2. There is acidaemia.
  3. The PaCO2 is not compensating for the acidaemia.
  4. The SBE is -18, suggesting a severe metabolic acidosis
  5. The respiratory compensation is inadequate- the expected PaCO2 (11 × 1.5) + 8 = 24.5mmHg, according to the Boston rules. Thus, there is also a respiratory acidosis.
    (Copenhagen rules can also be applied, and yield an expected PaCO2 of 22 mmHg)
  6. The anion gap is 14, according to the college.
    Assuming the albumin is normal, the AG is raised by 2.
    The delta ratio is therefore (2 / 13) = 0.15

Thus, this is a pure NAGMA and a respiratory acidosis.

A word of thanks is offered to one of the commentators for bringing attention to the fact that the college have used conventional arterial gas interpretation rules to interpret this venous sample. How valid is this practice? Let us reason though it.

Consider that mixing CO2 with blood will yield a predictable increase in HCO3- no matter where that blood is kept. Thus, the change in bicarbonate associated with acute hypercapnoea should be consistent on both sides of the circulation. However, the venous side of the circulation has a higher CO2. There may arise situations during which the venous CO2 is higher by a significant degree, giving rise to the impression that the respiratory compensation for metabolic acidosis is inadequate. Of course, that blood still has not yet passed through the pulmonary circulation, and so one cannot convincingly say that the respiratory system has failed at compensation (it hasn't even had a go yet). 

Thus, one might expect the venous gas to occasionally give a false impression of a mixed metabolic and respiratory acidosis (or, to fail to reveal a respiratory alkalosis). One can imagine that this might happen in states where the arterio-venous CO2 difference is somehow elevated. In fact, this has been demonstrated experimentally, in dissertations by Murphy (1982) and Berner (1983) who used exsanguinating dogs. The arteriovenous CO2 gap is thought to be a reasonably good marker of circulatory efficacy in shock states, good enough to guide therapy (Mallat et al, 2016). In contrast, it would appear that either there is probably little difference between arterial and venous samples during states with normal circulation, as demonstrated by Ilkiw et al (2008) whose dogs were not exsanguinating. 

So it it fair to say that the patient in this SAQ has a respiratory acidosis on the basis of a venous gas? Probably not, one should think. Sepsis and multi organ system failure do not sound like they describe a state of circulatory adequacy. However, the college examiners decided not to mention it. They seem to have just used the standard rules anyway. In their defense, it should be pointed out that in order for the corresponding arterial blood sample to have adequate compensation, the A-v CO2 difference would have to be about 18 mmHg, consistent with severe shock (it's meant to be under 6 mmHg).

In summary, the savvy exam candidate will be aware of this caveat, and be prepared to discuss it if questioned, but will probably be safe to ignore it in future venous blood gas questions.

b)

The college only asked for possible explanations of the acid-base disturbance. The generic causes of NAGMA are given below. Any of them could potentially be applicable.

References

Ilkiw, Jan E., R. J. Rose, and I. C. A. Martin. "A Comparison of Simultaneously Collected Arterial, Mixed Venous, Jugular Venous and Cephalic Venous Blood Samples in the Assessment of Blood‐Gas and Acid‐Base Status in the Dog." Journal of veterinary internal medicine 5.5 (1991): 294-298.

SIGGAARD‐ANDERSEN, Ole, and Ivar H. Gøthgen. "Oxygen and acid‐base parameters of arterial and mixed venous blood, relevant versus redundant." Acta Anaesthesiologica Scandinavica 39.s107 (1995): 21-27.

Griffith, K. K., et al. "Mixed venous blood-gas composition in experimentally induced acid-base disturbances." Heart & lung: the journal of critical care 12.6 (1983): 581.

Berner, Barbara J. "The Use of mixed venous blood to assess acid-base status in states of decreased cardiac output when respiration is controlled." (1983).

Murphy, Janet A. "The use of mixed venous blood for assessment of acid-base status in states of decreased cardiac output." (1982).

Mallat, Jihad, et al. "Use of venous-to-arterial carbon dioxide tension difference to guide resuscitation therapy in septic shock." World journal of critical care medicine 5.1 (2016): 47.

Question 4.3 - 2016, Paper 1

Define the terms 'base excess' and 'standard base excess' (20% marks)

College Answer

Base excess is defined as the amount of acid or alkali that must be added to fully oxygenated blood to return the pH to 7.40 at a temperature of 37°C and a pCO2 of 40 mmHg.

Standard base excess is the amount of acid or alkali to return the ECF pH to 7.40 at a temperature of 37°C and a pCO2 of 40 mmHg and is calculated for blood at a Hb of 50 g/L.

Discussion

In brief:

Base excess definition

  • Dose of acid or base required to return the pH of a blood sample
  • Measured at standard conditions: 37°C and 40mmHg PaCO2
  • Thus, isolates the metabolic disturbance from the respiratory

Standard base excess

  • Dose of acid or base required to return the pH of an anaemic blood sample
  • Calculated for a Hb of 50g/L
  • Haemoglobin buffers both the intravascular and the extravascular fluid
  • Thus, SBE assesses the buffering of the whole extracellular fluid, not just the haemoglobin-rich intravascular fluid

References

Reade, M. C. "Temporary epicardial pacing after cardiac surgery: a practical review." Anaesthesia 62.3 (2007): 264-271.

Reade, M. C. "Temporary epicardial pacing after cardiac surgery: a practical review: Part 2: Selection of epicardial pacing modes and troubleshooting."ANAESTHESIA-LONDON- 62.4 (2007): 364.

Gammage, Michael D. "Temporary cardiac pacing." Heart 83.6 (2000): 715-720.

Sanders, Richard S. "The Pulse Generator." Cardiac Pacing for the Clinician. Springer US, 2008. 47-71.

Question 8 - 2016, Paper 1

Critically evaluate the role of monitoring blood lactate levels in the critically ill

ollege Answer

Introduction:

Lactate measurement is easy, widely available and accurate. High blood lactate levels may represent increased production from tissues and/or decreased metabolic clearance.

Uses

  • End-point of resuscitation – lactate clearance.
  • Diagnosis of inadequate tissue oxygenation / ischaemia.
  • Risk stratification in ED and ICU – predictor of non-survival.
  • Prognostication and assessment of severity in liver disease.
  • Prognosis post cardiac arrest.
  • Lactate gap (lactate value from POC analyser – lactate value from lab) assists diagnosis in ethylene glycol toxicity.

Evidence:

  • Lactate levels proportional to mortality – lactate ≥ 4 is associated with poorer outcome.
  • Poor lactate clearance in trauma patients associated with bad prognosis.
  • High lactate levels may indicate underlying sepsis in patients who otherwise appear stable (in Rivers EGDT in sepsis trial, 50% patients with MAP >100 had high lactate).
  • Multi-centre study of 100 patients post cardiac arrest showed lower lactate levels in first 24 hours and increased lactate in first 12 hours post arrest were associated with survival and good neurological outcome.
  • Sustained high levels of lactate in paracetamol toxicity related ALF may be a trigger for need for transplantation.

Three studies have looked at lactate-directed versus non-lactate-directed therapy in: 

  • Post-cardiac surgery patients – showed reduction in morbidity but not powered to look at mortality.
  • Septic patients in the ED – testing non-inferiority with ScvO2 showed no difference in outcomes although some limitations of study.
  • ICU patients with raised lactate levels – used GTN when ScvO2 normalised but lactate remained high. Showed statistically significant reduction in morbidity and trend to reduction in mortality but course of lactate levels in both groups was similar.

Practical points:

Monitoring alone does not improve outcome and treatment needs to target the underlying disease. Adequate understanding of the anaerobic and aerobic mechanisms of production and clearance is essential to correctly interpret the significance of raised lactate levels. Lactate levels should be interpreted with clinical correlation.

Lactate levels not useful in:

  • Elevated lactate levels with beta agonist therapy (increased lactate production from increased glycolytic flux).
  • Post seizures.

Overall: 

  • Lactate levels in critical illness not fully understood.
  • Lack of high-level evidence showing use of lactate monitoring improves outcomes.

Summary statement:

For example: Lactate appears to be an epiphenomenon and marker of severity in the critically ill. My practice is to use it as an end-point of resuscitation and an indicator of possible underlying tissue ischaemia in the shocked patient but not necessarily to react in patients who are otherwise haemodynamically stable with adequate tissue O2 delivery.

Additional comments:

Candidates were given credit for including valid points not included in the template. The detail of the studies given in the above template was not required for a pass mark.

Satisfactory answer for a pass mark was expected to include:

  • The uses of lactate monitoring 
  • Some reference to the supporting evidence
  • Limitations of lactate monitoring

Discussion

Rationale for lactate monitoring in critical illness

  • Lactate is a product of anaerobic metabolism
  • Anaerobic metabolism in human tissues is an abnormal physiological state, be it of poor tissue perfusion or impaired oxygen utilisation.
  • Lactate clearance is rapid in the presence of normal hepatic function
  • Serum lactate may therefore be useful as a biomarker, a measure of anaerobic metabolism.
  • Conditions which result in a raised lactate may not be easy to identify in critically ill patients (eg. ischaemic gut, ischaemic limbs, sepsis, etc) and so lactate levels may be the only feature of such conditions

Advantages of lactate monitoring in critical illness

  • A simple test, widely available, and can be performed as a part of blood gas analysis
  • Venous and arterial lactate levels correlate conveniently
  • Lactate is cheap to test - there may be a saving in healthcare costs
  • Its clearance by kidneys and dialysis is proportionally poorer than hepatic clearance, which means as a biomarker it is neither obscured by dialysis nor falsely elevated in the presence of renal failure.

Errors of lactate measurement

  • Storage delay: metabolism by blood cells can cause an elevated lactate
  • Collection error: A sample accidentally mixed with compound sodium lactate will cause a spuriously elevated lactate level.
  • Measurement error: a "lactate gap" is generated when the lactate-sensing electrode in the b;lood gas machine confuses lactate with ethylene glycol

Errors of lactate interpretation

  • Tissue perfusion may be normal, and lactate clearance may be impaired (as in liver disease)
  • Lactate may be raised due to poor tissue oxygen utilisation, rather than poor perfusion (eg. in septic shock)
  • Lactate may be raised in the absence of acidosis (eg. exogenous compound sodium lactate administration).
  • Lactate may be raised because of increased production by abnormal metabolic processes in neoplastic tissue

Evidence for and against the use of lactate as a biomarker

Lactate as a prognostic marker:

  • It correlates well with mortality in sepsis: patients with a presenting lactate over 4.0mmol/L were almost five times more  likely to die (Mikkelsen et al, 2009)
  • High levels may reveal underlying "occult" sepsis in otherwise stable patients (Rivers et al, 2001).
  • It is associated with a poor prognosis in trauma. Specifically, failure to normalise the lactate over the first 2 days is associated with worse organ failure and increased mortality (Manikis et al, 1995)
  • It predicts poor recovery from cardiac arrest. Survivors and patients with good neurological outcome had lower lactate levels at 0, 12 and 24 hours (Donnino et al, 2015 is the 100-patient study mentioned by the college)
  • It acts as a trigger for liver transplatation: lactate predicts non-survivors from paracetamol toxicity earlier than the King's College Criteria (Bernal et al, 2002). However, somehow the effect of adding lactate to the King's College Criteria actually decreases their diagnostic odds ratio slightly, from about 27 to about 26. (Craig et al, 2010)

Lactate as a guide to therapy:

  • In sepsis, it is non-inferior to mixed venous saturation as a goal of early sepsis therapy (Jones et al, 2010).
  • Following cardiothoracic surgery, it can be used to guide therapy in haemodynamically unstable patients (though neither Pölönen et al in 2000 nor Shrestha et al in 2015 were able to demonstrate a statistically significant mortality benefit, because their studies were underpowered)
  • To target the use of GTN when ScvO2 normalised but lactate remained high : The literature on the subject is somewhat mixed. As an example, in 2010 Janssen et al used GTN to optimise the microcirculation along with several other EGDT-era manoeuvres (eg. the use of CVP to guide fluid responsiveness). GTN infusion was commenced if the lactate levels did not fall with conventional therapy even after the ScvO2 had returned to normal. Eight hours of such lactate-guided therapy produced a mortality reduction from 43.5% to 33.9%, which is weird because there was no difference in the lactate levels between the groups.  Ther practice is also mentioned in the review by Bakker et al (2013, where one of the et als was Janssen), where an (unpublished?) study by Lima et al (2012) is discussed, using GTN to normalise lactate . Bakker (also a co-author of Lima et al, 2012) was critical of this technique in his later review article, saying that the evidence did not support this use of lactate monitoring (or GTN infusion). 

References

Jansen, Tim C., Jasper van Bommel, and Jan Bakker. "Blood lactate monitoring in critically ill patients: A systematic health technology assessment*." Critical care medicine 37.10 (2009): 2827-2839.=

Okorie, Okorie Nduka, and Phil Dellinger. "Lactate: biomarker and potential therapeutic target." Critical care clinics 27.2 (2011): 299-326.

Mikkelsen, Mark E., et al. "Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock*." Critical care medicine 37.5 (2009): 1670-1677.

Manikis, Panagiotis, et al. "Correlation of serial blood lactate levels to organ failure and mortality after trauma." The American journal of emergency medicine 13.6 (1995): 619-622.

Jones, Alan E., et al. "Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial." Jama 303.8 (2010): 739-746.

Fuller, Brian M., and R. Phillip Dellinger. "Lactate as a hemodynamic marker in the critically ill." Current opinion in critical care 18.3 (2012): 267.

Bakker, Jan, Maarten WN Nijsten, and Tim C. Jansen. "Clinical use of lactate monitoring in critically ill patients." Annals of intensive care 3.1 (2013): 1.

Shrestha, K. R., B. Pradhan, and B. Koirala. "A prospective randomized study of goal oriented hemodynamic therapy in cardiac surgical patients." Journal of Institute of Medicine (2015).

Lima A, van Genderen M, Van Bommel J, Bakker J: "Nitroglycerine dose-dependent improves peripheral perfusion in patients with circulatory shock: results of a prospective cross-over study". Intensive Care Med 2012, 38(Suppl 1):S127.- cited in Bakker et al, 2013

Bernal, William, et al. "Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study." The Lancet 359.9306 (2002): 558-563.

Jansen, Tim C., et al. "Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial." American journal of respiratory and critical care medicine 182.6 (2010): 752-761.

Question 13.1 - 2016, Paper 2

A 26-year-old male found was collapsed in the street. On arrival in the Emergency Department, he was unresponsive and hypotensive with a temperature of 42°C. The following is his arterial blood gas result following intubation:

Parameter

Patient Value

Normal Adult Range

Fi02

1.0

pH

7.21*

7.35 - 7.45

PC02

54 mmHg (7.1 kPa)*

35 - 45 (4.6 - 6.0)

P02

500 mmHg (65.8 kPa)

Bicarbonate

21 mmol/L

21 - 28 (10 - 13)

Base Excess

-6 mmol/L*

-2 - +2

Sodium

143 mmol/L

135 - 145

Potassium

4.9 mmol/L*

3.5 - 4.5

Chloride

112 mmol/L*

95 - 110

Calcium ionised

1.09 mmol/L*

1.12 - 1.32

Glucose

9.6 mmol/L*

3.0 - 5.4

Lactate

2.3 mmol/L*

< 1.3

Creatinine

219 µmol/L*

60 - 110

Haemoqlobin

139 q/L

135 - 180

a) Describe the acid-base abnormality. (20% marks)

b) Give the likely underlying cause for this clinical picture. (15% marks)

College answer

a)    Mixed respiratory, high anion gap and normal anion gap metabolic acidosis.      
 
b)    Toxidrome – sympathomimetic agent.      
 

Discussion

a)

Let us dissect these results systematically.

  1. The A-a gradient is raised; at 100% FiO2 the PaO2 should be 645mmHg
  2. There is acidaemia
  3. The PaCO2 is contributing
  4. The SBE is -6, suggesting a mild metabolic acidosis
  5. The respiratory compensation is inadequate - the expected PaCO2 (21 × 1.5) + 8 = 39.5mmHg, and so there is also a respiratory acidosis according to the Boston rules.
  6. The anion gap is essentially normal:
    (143) - (112 + 21) = 10, or 14.9 when calculated with potassium. 
    It is not clear where the college gets their answer from, as typically they both omit potassium and use normal values for the anion gap which are probably anachronistic in this era of ion-sensing electrodes. Even with new values and with poassium included, it is impossible to generate a delta ratio in the 0.4-0.8 range.

The college only wanted us to comment on the acid-base abnormalities, but other features are also interesting. In summary:

  • Decreased level of consciousness
  • Extreme hyperthermia
  • Hypotension
  • Raised creatitinine, which could be
    • due to acute renal failure in the context of shock
    • due to rhabdomyolysis
  • Slightly low calcium (consistent with rhabdomyolysis, if that's what is happening)

b)

Informed by the above features, the differentials must include:

  • Heat stroke
  • Neuroleptic-malignant syndrome
  • Serotonin syndrome
  • Seizures
  • Amphetamine toxicity
  • Sepsis

If he didn't come from the street, malignant hyperthermia would also have to be mentioned.

References

Question 17.1 - 2016, Paper 2

A 75-year-old female, with a past history of Parkinson's disease and a recent admission for behavioural disturbance, presents with a fluctuating conscious state. Her temperature is 37.2°C, respiratory rate 26 breaths/min, blood pressure 100/80 mmHg, pulse rate 100 beats/min, and Sp02 98% on 0.4 Fi02.

Her investigations are as follows:

Parameter

Patient Value

Normal Adult Range

Haemoglobin

85 g/L*

115 - 160

White Cell Count

20.9 x 1O\l/L*

4.0 - 11.0

Platelets

82 x 1O\l/L*

150 - 400

Albumin

34 q/L

35 - 50

Total Bilirubin

10 µmol/L

< 20

Alanine  aminotransferase

421 U/L*

< 35

Alkaline phosphatase

60 U/L

30 - 110

y-Glutamyl transferase

23 U/L

< 40

Sodium

140 mmol/L

135 - 145

Potassium

3.4 mmol/L*

3.5 - 5.2

Bicarbonate

12 mmol/L*

22 - 32

Chloride

103 mmol/L

100 - 110

Urea

3.6 mmol/L

3.0 - 8.0

Creatinine

88 umol/L

45 - 90

Lactate

17 mmol/L*

< 2

International normalised ratio

2.9*

0.9 - 1.3

Activated partial thromboplastin time

58.0 sec*

25 .0 - 37.0

Fi02

0.4

pH

7.21*

7.35 - 7.45

PC02

25 mmHg (3.3 kPa)*

35 - 45 (4.6 - 6.0)

P02

204 mmHq (26.8 kPa)

Bicarbonate

10 mmol/L*

22 - 26  

a) Comment on her acid-base status. (20% marks)

b) List three differential diagnoses for this patient's presentation, with confirmatory investigations for each. (50% marks)

College answer

a)

Raised anion gap metabolic acidosis, lactic acidosis, with appropriate respiratory compensation (Anion gap 143 – 115 = 28)

b)

  • Sepsis / Septic shock – Meningo-encephalitis, biliary, urinary § Blood, Urine cultures
    • CT brain or chest/abdo
    • LP
  • Drug toxicity: quetiapine, side effects of Parkinson‟s meds, paracetamol
    • Urinary drug screen
    • Paracetamol levels
  • Seizures
  •  EEG
  • Ischaemic gut less likely but possible
  • CT abdo
  • Serotonin syndrome – less likely
  • CK
  • Acute liver failure unlikely as LFTs only mildly deranged, bilirubin normal and although coagulopathy, albumin is normal

Discussion

Let us dissect these results systematically.

  1. The A-a gradient is slightly raised; at 40% FiO2 the PaO2 should be 253.9 mmHg
  2. There is acidaemia
  3. The PaCO2 is appropritely low
  4. The SBE is not offered, but the bicarbonate is 10, suggesting a severe metabolic acidosis
  5. The respiratory compensation is adequate - the expected PaCO2 (10 × 1.5) + 8 = 23mmHg, close enough to the actual measured value.
  6. The anion gap is raised: (140) - (103 + 12) = 25, or 28.4 when calculated with potassium. Again, this is one of these rare ABG questions where the college examiners decided to include potassium in the calculation, though judging by their working they only included some of the potassium (3.0mmol instead of 3.4).
    Anyway. The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (25 - 12) / (24 - 12) = 1.08. 
    Thus this is probably a pure high anion gap metabolic acidosis). The lactate is raised (17), which probably accounts for much (all!) of this anion gap change.

Thus, this is a pure lactic acidosis.

b)

Causes of such extreme lactic acidosis?

  • Sepsis. the WCC is elevated and there is depletion of platelets and clotting factors. One would send cultures and inflamatory markers
  • Seizures. Both anti-Parkinsons drugs and antipsychotics lower the seizure threshold. This lady has recently been admitted for come sort of delirium- who knows what pharmacological agents were used to keep her quiet. One would send a CK level and perform an EEG.
  • Liver disease. The LFTs are deranged, and there is thrombocytopenia and coagulopathy. This lady's earlier confusion could be accounted for by hepatic encephalopathy. The lactate might be raised because of a failure of its clearance. Wilsons' disease is a possibility, given that Parkinsonian symptoms are common in that group. Serum ceruloplasmin and serum copper are the correct tests.
  • Thiamine deficiency. The haemoglobin is low, raising the possibility of macrocytic anaemia. Red cell transketolase would be an appropriate test (however, this condition has already come up earlier in this paper, so thiamine deficiency is unlikely to be the answer).

References

Question 17.2 - 2016, Paper 2

A 60-year-old male presents following a generalised tonic clonic seizure. He has chronic abdominal pain and Crohn's disease with previous complicated small bowel surgery resulting in an ileostomy. The seizure spontaneously resolves after 3 minutes.

Blood investigations taken after the seizure are as follows:

Parameter

Patient Value

Normal Adult Range

Sodium

135 mmol/L

135 - 145

Potassium

2.5 mmol/L*

3.5 - 5.2

Chloride

105 mmol/L

100 - 110

Bicarbonate

11 mmol/L*

22 - 32

Lactate

6.8 mmol/L*

< 2.0

Calcium (Total)

1.45 mmol/L*

2.15 - 2.60

Maqnesium

0.28 mmol/L*

0.70 - 1.00

Fi02

pH

7.06*

7.35 - 7.45

PC02

40 mmHQ (5.3 kPa)

35 - 45 (4.6 - 6.0)

P02

280 mmHg (37 kPa)

Bicarbonate

11 mmol/L*

22 - 26

a) What is the likely cause of his seizure? (10% marks)

b) Describe and explain the acid-base abnormality with potential causes. (20% marks)

College answer

a)      
Hypomagnesemia. 
Other possibility is hypocalcaemia however corrected and iCa++ not given. 
  
b)      
•    Severe metabolic acidosis 
•    Concurrent respiratory acidosis (CO2 high for bicarbonate) o Respiratory depression post seizure 
•    High anion gap due to lactic acid o Seizure activity 
•    Concurrent normal anion gap acidosis (Delta Ratio 0.7) 
o GI loses from high output stoma o RTA e.g. from NSAIDs for analgesia  o Chloride resuscitation 
 

Discussion

a)

The most likely cause of the seizure is electrolyte derangement. The magnesium is probably the biggest culprit. Interestingly, case reports of such things have been published (eg. Fernández-Rodríguez et al, 2007). Seizures disappeared when the magneisum was corrected.

b)

Let us dissect these results systematically.

  1. The A-a gradient is not calculated, and presumed to be near normal
  2. There is acidaemia
  3. The PaCO2 is unhelpfully high.
  4. The SBE is not offered, but the bicarbonate is 11, suggesting a severe metabolic acidosis
  5. The respiratory compensation is inadequate - the expected PaCO2 (11 × 1.5) + 8 = 24.5mmHg, and so there is also a respiratory acidosis (using the Boston rules)
  6. The anion gap is raised:
    (135) - (105 + 11) = 19, or 21.5 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (19 - 12) / (24 - 11) = 0.53. 
    That makes this a mixed high and normal anion gap metabolic acidosis.

The lactate is probably coming from the post-convulsive muscles, and the normal anion gap acidosis is probably the consequence of bicarbonate loss via the ileostomy (or, using a Stewardian explanation, it is the consequence of ineffective cation resorption by the shortened gut).

References

Fernández-Rodríguez, E., and E. Camarero-González. "[Patient with Crohn's disease and seizures due to hypomagnesemia]." Nutricion hospitalaria 22.6 (2006): 720-722.

Question 20.2 - 2017, Paper 1

A 46-year-o ld male presents with vomiting for the past five days.

His arterial blood gas result on room air is shown below:

Parameter

Patient Value

Adult Normal Range

pH

7.74*

7.35 -7.45

pCO2

48.5 mmHg (6.4 kPa)*

35.0 -45.0 (4.6 - 6.0)

pO2

80 mmHg (10.5 kPa)

80 - 100 (10.5 -13.0}

Bicarbonate

62 mmol/L*

20- 30

Base Excess

39.6 mmol/L*

-2.0 - +2.0

SpO2

97.6%

95.0 -98.0

Sodium

131 mmol/L*

135 - 145

Potassium

3.1 mmol/L*

3.5 - 5.0

Chloride

47 mmol/L*

95 - 105

Glucose

10.5 mmol/L*

3.5 - 6.0

Lactate

5.6 mmol/L*

< 2.0

Describe the acid-base derangements seen        (30% marks)

College answer

  • Profound metabolic alkalosis with inadequate respiratory compensation
  • Lactic acidosis (raised anion gap)

Discussion

Let us dissect this systematically:

  1. The A-a gradient is about 10 (alveloar O2 is about 89 mmHg). There is no problem with gas exchange.
  2. There is severe alkalaemia
  3. The CO2 is appropriately elevated
  4. There is metabolic alkalosis; SBE is 39.6 mmol/L
  5. The compensation is probably inadequate, and the extreme example demonstrates the limitations of compensation. The expected CO2 by Boston rules is (62 × 0.7) + 20 = 63.4 mmHg; the SBE-based Copenhagen rules give us a number closer to 64 mmHg. Either way, the rules of compensation recommend a CO2 level which approaches the maximal possible level for compensation. With an alveolar CO2 of 64 on room air, the alveolar oxygen tension would be around 55-60 mmHg, which means hypoxia would drive the respiratory rate (alkalaemia being a relatively weak depressant of respiratory drive). 
    In any case, there is inadequate respiratory compensation.
  6. The potassium is low and the lactate is high, which is consistent with hypovolaemia. The patient is severely dehydrated and this has stimulated aldosterone secretion, worsening the alkalosis and promoting hypokalemia. 

References

Question 20.3 - 2017, Paper 1

The following arterial blood gas result was obtained from a 70-year-old female with type 2 diabetes, presenting with acute exacerbation of asthma.

Parameter

Measured Value

Adult Normal Range

Fi02

0.21

pH

7.21'

7.35 - 7.45

PaCO2

60 mmHg (8.0 kPa)*

35 -45 (4.6 - 6.0)

PaO2

55 mmHg (7 kPa)

Bicarbonate

23 mmol/L

22 - 27

Base Excess

-4 mmol/L*

-2 - +2

Sodium

135 mmol/L

135 - 145

Potassium

5.3 mmol/L*

3.5 - 5.0

Chloride

100 mmol/L

100 - 110

Glucose

9.2 mmol/L*

3.5 - 6.0

Urea

8.3 mmol/L*

3.5 -7.2

Creatinine

120 umol/L*

50 - 100

Lactate

4.8 mmol/L*

< 2.0

HbA1c

11.0 mmol/mol*

50 -60

Describe the abnormalities in the above results, giving likely explanations             (30% marks)

College answer

  • Normal A-a gradient (20) for 70 year old – hypoventilation
  • Respiratory acidosis – acute type 2 respiratory failure tiring from acute asthmatic attack
  • Normal anion gap metabolic acidosis  – underlying type IV RTA secondary to diabetic  nephropathy (or any reasonable cause)
  • Hyperlactataemia – beta-2 agonist induced
  • Hyperkalaemia and raised creatinine- renal impairment
  • Poor diabetic control (high BSL and HbA1C) 

Discussion

Let us dissect this systematically;

  1. The patient is hypoxic (PaO2 of 55 mmHg) but the A-a gradient is minimally raised (~ 19) which suggests that alveolar hypoventilation is the main cause of the hypoxia.
  2. There is acidaemia
  3. The CO2 is contributing to the acidaemia
  4. The SBE is -4, suggesting that there is also a mild metabolic acidosis
  5.  The urea and creatinine are slightly raised, reflecting the possibility that in this asthma episode the patient has been too breathless to eat and drink normally.
  6. The lactate is raised, suggesting that salbutamol is being administered (or else, that hypovolaemia is quite severe)
  7. The glucose is slightly elevated and the HbA1c is raised, suggesting that this patient is a diabetic and their attention to their BSl control is patchy and haphazard
  8. Now, to the acid-base disturbance. The anion gap is (135) - (100 + 23) = 12, or 17.3 when calculated with potassium. Thus, this is a normal anion gap acidosis.

Let's explore that anion gap reference value. 

According to the RCPA, the anion gap range with potassium is 8-16, i.e. you'd take 12 as the middle reference value for delta ratio calculations. Without potassium the range is 4-13, i.e. the reference value would be 8.5. Unfortunately the RCPA use Sirker et al (2002) as their reference, an article which completely ignores this issue and gives no reference ranges. So, I am not sure where they got their numbers from; I only used them because of their relatively weighty authority (Royal College, etc).

However, they seem legit: the change in reference values from the higher values (16 with potassium, 12 without) is due to a change in measurement methodology and laboratory reference ranges which appears to have occurred in the late 1980s-early 1990s (Winter et al, 1990).  The reference ranges are always based on healthy volunteers who should have no acid-base disturbances, and those guys have not changed, but now we tend to use ion-selective electrodes instead of older photometric methods, a practice which has shifted the reference range for the anion gap into a lower range (mainly because of a drift in the chloride measurements).  There’s a few studies reporting this change in the last 20 years (and it’s always different, 5-10 mmol/L, or 3-11 mmol/L or, 4-12 mmol/L). A representative paper is Lolekha et al (2001) who got a range of 5-12 mmol/L.

However, this knowledge is of absolutely no use to the CICM trainee, because the college examiners continue using the pre-1990s reference ranges. 

If we use the (slightly different) modern reference ranges, we get significantly different results, because the numbers involved here are also quite small, near the borders of normality (obviously the change in reference ranges is going to play a minimal role whenever the acid-base disturbance is profound and obvious). Let's use the with-potassium formula for the anion gap. We get an anion gap of 17.3, and assuming the albumin is normal we would expect a normal value of 12, which means it has risen by 5.3.  The delta ratio is therefore 5.3 / 1.0 = 5.3, i.e it points to a co-existing metabolic alkalosis.   If you omit the use of potassium in the anion gap equation you get an anion gap of 12; with an expected normal anion gap value of  8.5 the delta ratio is still 3.5. 

References

Sirker, A. A., et al. "Acid− base physiology: the ‘traditional’and the ‘modern’approaches." Anaesthesia 57.4 (2002): 348-356.

Lolekha, Porntip H., Somlak Vanavanan, and Somsak Lolekha. "Update on value of the anion gap in clinical diagnosis and laboratory evaluation." Clinica chimica acta307.1-2 (2001): 33-36.

Winter, Sara D., et al. "The fall of the serum anion gap." Archives of internal medicine 150.2 (1990): 311-313.

Question 20.2 - 2017, Paper 2

A 58-year-old female presents following an intentional overdose. Her arterial blood gases are presented below:                                                                                              
 

Parameter Patient Value Adult Normal Range
Fi02 0.21  
pH 7.36 7.35 - 7.45
pC02 16.0 mmHg (2.13 kPa)* 35.0 - 45.0 (4.60 - 6.00)
p02 111 mmHg (14.8 kPa)  
Sp02 97%  
Bicarbonate 9.0 mmol/L* 22.0 - 26.0
Base Excess -15.0 mmol/L* -2.0 - +2.0
Lactate 25.0 mmol/L* 0.5 - 1.6
Sodium 150 mmol/L* 135 - 145
Potassium 4.5 mmol/L 3.5 - 5.0
Chloride 117 mmol/L* 95 - 105
Glucose 4.0 mmol/L 3.5 - 6.0

a) Describe the acid base abnormalities. (40% marks)


Her lactate as measured on ABG is 25 mm/L, but the result on a blood sample taken at the same time and measured in the laboratory is only 5 mmol/L.

b) What is the most likely diagnosis? Explain the mechanism of the differences in measured lactates.
(20% marks)

College answer

a)  

  • Metabolic acidosis and respiratory alkalosis  
  • Elevated anion gap  
  • Delta AG/Delta HCO3- 0.8 evidence of non-anion gap acidosis
  • Elevated lactate

b)  

  • Ethylene glycol toxicity
  • Less commonly reported = paracetamol and isoniazid
  • Ethylene glycol itself is not involved in lactate production.
  • EG metabolites (glycolic and glyoxylic acid) react with the analytical reagant L-lactate oxidase used in lactate electrodes which equip many blood gas analyses due to similar structures with lactic acid.  Serum lactate measured using a different technique so “lactate gap” develops

Specific details of the assays not required.

Discussion

To go though it systematically:

  • There is normoxia on room air.
  • The pH is normal
  • There is a severe metabolic acidosis (SBE < 15)
  • The CO2 is inappropriately low (it should be around 25 mmHg) and so there is also a respiratory alkalosis
  • The anion gap is (150 + 4.5 - 117 - 9) = 28.5. Or, if you omit potassium, it is 24. With the first value, assuming a normal albumin, the anion gap is raised by 16.5 and the bicarbonate is depressed by 15, which gives a delta ratio of 1.1 - i.e. this is a pure high anion gap metabolic acidosis. With omission of the potassium, the delta ratio is 0.8. 

This (apart from demonstrating the limitations of the anion gap and delta ratio as diagnostic instruments) also illustrates the diversity in presentations. By classical teaching, you'd expect ethylene glycol toxicity to generate a pure high anion gap metabolic acidosis. However, it turns out almost half of these patients have a raised chloride and a degree of NAGMA (Soghoian et al, 2008). The mechanisms for this are not completely understood- the authors lament their lack of access to data regarding urinary ammonia and suchlike. Their hypothesis was that the high fractional urinary excretion of anionic metabolites of ethylene glycol depresses the HAGMA component, exaggerating the NAGMA which is produced by the renal failure associated with oxalate. 

The "lactate gap" to which this question refers to is due to the lactate electrode being confused by the glycolic acid in her bloodstream. The patient has obviously overdosed on ethylene glycol. We know this because this SAQ draws on a classic ABG question (Question 1.12) from the 2003 edition of Data Interpretation in Intensive Care Medicine by Bala Venkatesh et al. 

The amperometric measurement of lactate uses the lactate-sensitive electrode ("which equip many blood gas analyses"), relying on the use of lactate oxidase. This enzyme catalyses the reaction which converts lactate into pyruvate, producing hydrogen peroxide which is reduced at the measurement cathode. Glycolic acid, the metabolic byproduct of ethylene glycol metabolism, also acts as the substrate for this enzyme. Therefore, in ethylene glycol poisoning the lactate measurement by the blood gas analyser will be spuriously elevated. The formal lactate measurement by use of a lactate dehydrogenase enzyme assay will still yield a correct result. The difference between the "formal" and the ABG lactate is described as the "lactate gap", and is a well known phenomenon of ethylene glycol toxicity (eg. Marwick et al, 2012).  Apart from paracetamol and isoniazid as other potential culprits, the Reference Manual for the local ABG analyser lists a large number of molecules which can potentially cause interference with lactate measurement- notably ascorbic acid, bilirubin, citrate, EDTA, ethanol, heparin, glucose, paracetamol, salicylate and urea.

References

Marwick, J., R. O. C. Elledge, and A. Burtenshaw. "Ethylene glycol poisoning and the lactate gap." Anaesthesia 67.3 (2012): 299-299.

Soghoian, Sari, et al. "Ethylene Glycol Toxicity Presenting with Non‐Anion Gap Metabolic Acidosis." Basic & clinical pharmacology & toxicology 104.1 (2009): 22-26.

Question 4.1 - 2017, Paper 2

4.1
The following results are from a 35-year-old female with fever, shortness of breath and known renal calculi.

Parameter

Patient Value

Adult Normal Range

Fi02

0.21

 

pH

7.30*

7.35 - 7.45

pC02

25.0 mmHg (3.3 kPa)*

35.0 - 45.0 (4.6 - 6.0)

p02

117 mmHg (15.6 kPa) /

 

Sp02

98%

 

Bicarbonate

12.0 mmol/L*     /

22.0 - 26.0

Base Excess

-15.0 mmol/L*
'

-2.0 - +2.0

Lactate

1.7 mmol/L* .,

0.5 - 1.6

 

Sodium

135 mmol/L

135 - 145

Potassium

4.1 mmol

3.5 - 5.0

Chloride

105 mmol/L

95 - 105/

Glucose

5.8 mmol/L

3.5 - 6.0

Creatinine

324 µmol/L*

45 - 90

Urea

29.0 mmol/L*  '

3.0 - 8.0

Albumin

42 g/L

35 - 50


a) Describe the acid base abnormalities. (30% marks)


b) Suggest one likely aetiology. (20% marks)

College answer

a)    Describe the acid base abnormalities.                               
 
Metabolic acidosis  
Anion gap elevated (18) 
Delta ratio 0.5 – so coexisting normal AG acidosis 
 
b)    Suggest one likely aetiology.                                    
 
Renal tubular acidosis (type 1) secondary to renal stones for NAGMA and urosepsis for HAGMA

 Guidance – any plausible answer that addresses all the acid-base abnormalities 
 

Discussion

A systematic approach:

  1. The patient is normoxic (PaO2 of 117 mmHg) and the A-a gradient is 1.5mmHg, which suggests that alveolar ventilation is satisfactory and there is probably no major gas exchange problems. 
  2. There is acidaemia.
  3. The CO2 is appropriately depressed. The expected CO2 is in fact 25 (by SBE method or by using the Boston rules).
  4. The SBE is -15, suggesting that there is a severe metabolic acidosis
  5. The anion gap is (135) - (105 + 12) = 18, or 22.1 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (18 - 12) / (24 - 12) = 0.5
    Thus, . there is a mixed high and normal anion gap metabolic acidosis.

The urea and creatinine are significantly raised, suggesting acute kidney injury.

The lactate is minimally raised, suggesting that retained non-volatile acids of renal failure are mainly responsible for the raised anion gap.

Given the history of renal calculi and fever, one might surmise that this lady probably suffers from an untreated renal tubular acidosis (as RTA Type I and Type II are associated with nephrolithiasis) and now has obstructive uropathy because of the stones. The fever may mean the stones are infected, but we got no information about any of that, so it falls in the realm of wild speculation. "Any plausible answer", etc.

References

Question 4.2 - 2017, Paper 2

A 69-year-old male has been intubated and ventilated  in the Emergency Department for worsening respiratory distress and abdominal pain. He was diagnosed with oesophageal cancer 3 months ago and has received chemotherapy followed by an oesophageal stent. He has non-insulin dependent diabetes.

The following blood results were obtained:

Parameter               Patient Value         Adult Normal Range
Fi02               0.5                      
pH               7.13*               7.35 - 7.45
p02               253 mmHg (33 kPa)              
pC02               25.0 mmHg (3.3 kPa)*     35.0 - 45.0 (4.6 - 6.0)
Sp02               99%                      
Bicarbonate             8.0 mmol/L*           22.0 - 26.0
Base Excess             -19.0 mmol/L*         -2.0 - +2.0
Lactate               10.0 mmol/L* ./         0.5 - 1.6  
                                         
Sodium               136 mmol/L           135 - 145
Potassium               4.6 mmol/L           3.5 - 5.0  
Chloride               103 mmol/L           95 - 105  
Glucose               15.5 mmol/L*           3.5 - 6.0  
Urea               54.0 mmol/L*           3.0 - 8.0  
Creatinine               644 µmol/L*           45 - 90  
Albumin               20 g/L*             35 - 50  
Ionised calcium             1.15 mmol/L           1.10 - 1.35

Interpret the data provided and give likely causes for the abnormalities in this patient.    (50% marks)

College answer

Interpret the data provided and give likely causes for the abnormalities in this patient      
 
Increased Aa gradient – aspiration, ARDS, fluid overload – any plausible cause 
High anion gap metabolic acidosis, elevated lactate – sepsis in immunosuppressed individual, consider oesophageal perforation, cardiac failure, metformin toxicity 
Respiratory acidosis – primary lung pathology, inadequate ventilator settings for degree of acidosis 
Delta ratio 1.1 (taking into account albumin)  
Renal impairment- sepsis, dehydration,  
Hyperglycaemia, low albumin – diabetes, stress response, malnutrition. 
 
Guidance to examiners: answers which are more specific to the known patient problems score more 
– e.g. oesophageal perforation, metformin toxicity 

 

Discussion

The history offered here suggests strongly that the gas exchange and metabolic problem is probably related to the oesophageal stent somehow.

A systematic dissection of these results:

  1. The patient is hyperoxic (PaO2 of 253 mmHg) and the A-a gradient is raised (72.3mmHg)
  2. There is acidaemia.
  3. The CO2 is appropriately depressed.  The expected CO2 is in fact 21 (by SBE method) or 20 (by using the Boston rules), and so there is also be a mild respiratory acidosis.
  4. The SBE is -19, suggesting that there is a severe metabolic acidosis
  5. The anion gap is  (136) - (103 + 8) = 25, or 29.6 when calculated with potassium.
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (25 - 12) / (24 - 8) = 0.81. Even though we have been recently instructed not to correct the anion gap for albumin "unless otherwise specified in the question stem",  the college examiners here clearly did expect the candidates to do this even though the stem does not mention it.  Seeing that the albumin is 20 we would expect an anion gap of 7.0, which means that the delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (25 - 12) / (24 - 8) = 1.12.
    Thus, unless one corrected the anion gap, one would not realise that this is a pure high anion gap metabolic acidosis.

The lactate is 10, which does not completely account for the change in the anion gap. One might interpret the raised glucose and sky-high urea and creatinine as signs that the patient is severely dehydrated and has some contribution from diabetic ketoacidosis (even though NIDDM is stated in the college question). The alternative explanation is uraemia, i.e. the retention of non-volatile acids in renal failure.  

References

Question 5.1 - 2018, Paper 1

A 68-year-old female with type 2 diabetes mellitus and hypertension has been unwell for a week with a history of abdominal pain, vomiting and loss of appetite. She was brought to the Emergency Department where she is found to be hypothermic, hypotensive and delirious.

Her blood test results are shown below:

Parameter

Patient Value

Adult Normal Range

Fi02

0.6

pH

7.07*

7.35 - 7.45

P02

125 mmHg (16.67 kPa)

PC02

18.0 mmHg (2.53

35 . 0 —45.0 (4.60 — 6.00)

Sp02

Bicarbonate

5.0 mmol/L*

22.0 - 26.0

Base Excess

-23.0 mmol/L*

_2,0 _ +2.0

Lactate

11.5 mmol/L*

0.5-1 6

Sodium

141 mmol/L

135 - 145

Potassium

5.4 mmol/L*

3.5 - 5.0

Chloride

93 mmol/L*

95- 105

Glucose

9.2 mmol/L*

3.5 - 6.0

Urea

29.0 mmol/L*

3.0 - 8.0

Creatinine

372 umol/L*

45 — 90

Ionised calcium

1.26 mmol/L

1.10 - 1.35

Calcium corrected

2.41 mmol/L

2.12 - 2.62

Phosphate

3.17 mmol/L*

0.80 - 1.50

Creatinine Kinase

99 u/L

55 - 170

Haemoglobin

77 g/L*

120 - 160

White Cell Count

16.4 x 109/L*

4.0 - 11.0

Platelet count

296 x 109/L

150 - 350

a) Describe the abnormalities in her blood test results and give a possible cause for each.
(30% marks)

b) List six other investigations you would order. (30% marks)
 

College answer

a)

1. Severe HAGMA Anion gap 43 – sepsis, shock from any cause 2. Lactic acidosis – ischaemic bowel, sepsis, metformin toxicity 
3.    Delta ratio 1.6, pure high anion gap acidosis as per a. 
4.    Hyperglycaemia, stress response, not high enough to be primary cause of metabolic abnormalities 
5.    Renal impairment – sepsis, shock, impaired perfusion 
6.    Hyperkalaemia and hyperphosphatemia likely secondary to renal impairment 7. Anaemia – sepsis 
8.    Leucocytosis – sepsis, stress response 
9.    Elevated A-a Gradient @ 292mmHg – aspiration, pneumonia 

 (Any plausible answer acceptable.)

b)

1.    Serum Ketones 
2.    Measured osmolality 
3.    Lipase 
4.    Septic screen 
5.    CXR 
6.    ECG and troponin 
7.    Transthoracic echocardiogram 
8.    CT abdomen (or USS) 
9.    Renal USS 
10.    LFT’s 
 

Examiner Comments:

 Examiners noted a lack of detail in some answers with anion gap or Aa gradient not mentioned.

Discussion

a)

Let's dissect this systematically. First, the acid-base disturbance

  • The patient is hypoxemic. The P/F ratio is 208.
  • If the atmospheric pressure is 760 and the alveolar gas mixture has an 100% relative humidity, the alveolar O2 partial pressure is 405 mmHg:
    0.6 × (760-47) - (18 / 0.8) = 405
    Thus, the A-a gradient is (405-125) = 280 mmHg. Where they got 192 from, one can only guess.
  • There is acidaemia.
  • There is a metabolic acidosis (the SBE is -23).
  • The CO2 is making an appropriate attempt at compensation; the expected CO2 is 17 mmHg according to the Copenhagen method, or (5 × 1.5) +8 = 15.5 mmHg according to the Boston rules  
  • The anion gap is raised, no matter how you calculate it (48.4 if you include potassium, and 43 if you do not).
  • The delta ratio is (43-12) / (24-5) = 1.63, which suggests this is a pure high anion gap acidosis. If you used potassium in your anion gap equation, you get 1.91 which still suggests a pure high anion gap acidosis.
  • The lactate is elevated, but the 11 mmol of lactate does not account for all of the anion gap or base deficit (in terms of mole-per-mole stoichiometry).

So, there is a high anion gap metabolic acidosis with appropriate respiratory compensation, which is only partly explained by the raised lactate. Scenarios which could explain this are:

  • Shock of any cause with acute renal failure
  • DKA/HHS
  • Intoxication with toxic alcohol (including ethylene glycol, in which case the lactate is spurious)

The other abnormalities (and explanations) are:

  • High potassium (renal failure, acidosis)
  • High phosphate (renal failure)
  • High glucose (stress response, or diabetes)
  • High urea and creatinine (acute or chronic renal failure)
  • Anaemia (chronic renal failure, acute blood loss, iron deficiency)
  • Elevated WCC (sepsis, steroids, stress response, vomiting, etc)

b)

Biochemistry

  • LFTs
  • Lipase
  • Inflammatory markers
  • Laboratory lactate
  • Serum ketones
  • Osmolality
  • Glycolic acid level

Imaging

  • CXR (respiratory source of sepsis)
  • ECG (myocardial infarction, tricyclic toxicity)
  • TTE (cardiogenic cause of shock)
  • CT of the abdomen
  • Renal tract ultrasound

References

Adrogué, Horacio J., and Nicolaos E. Madias. "Hypernatremia." New England Journal of Medicine 342.20 (2000): 1493-1499.

Question 12.1 - 2018, Paper 1

The following results were obtained from a 23-year-old female admitted with severe asthma.

Parameter

Patient Value

Adult Normal Range

Fi02

0.4

pH

6.92*

7.35 -7 45

P02

81 mmHg 10.8 kPa)

PC02

71.0 mmHg (9.5

350- . 45 0 . 4.6 — 6 0)

sp02

95%

Bicarbonate

14.0 mmol/L*

22.0 - 26.0

Base Excess

-16.0 mmol/L*

_2.0 _ +2.0

Lactate

9.0 mmol/L*

0.5 - 1.6

Sodium

139 mmol/L

135 - 145

Potassium

4.2 mmol/L

3.5-5 0

Chloride

108 mmol/L*

95 - 105

Glucose

19.2 mmol/L*

3.5 - 6.0

      a) Describe the abnormalities and give a potential reason for each.                           (30% marks)

College answer

Primary respiratory acidosis – likely secondary to asthma, 
Secondary high anion gap metabolic acidosis – shock, sepsis 
Concomitant non-anion gap metabolic acidosis – fluid resuscitation, (delta ratio 0.5) 
Increased Aa gradient – pulmonary sepsis 
Elevated lactate – sepsis, B2 agonist use 
Elevated glucose – pre-existing diabetes, stress, B2 agonist, steroids 
 

Discussion

The abnormalities addressed systematically are as follows:

1) There is no hypoxia per se, but the A-a gradient is widened (114)

2) There is profound acidaemia.

3) The CO2 is a major contributor to the acid-base disturbance.

4) There is a metabolic acidosis; the SBE is -16. As such, the expected CO2 is 28. To use the Boston rules,  the expected CO= (14 ×1.5) + 8 = 29, close enough for government work. Regardless of which acid-base church you follow, we should all be convinced that there is a combination of a severe metabolic acidosis with a severe respiratory acidosis.

5) The anion gap is (139 + 4.2) - (108 + 14) = 21.2, or 17 if you omit the potassium as the college frequently do.

6) The delta ratio is therefore either 0.92 or 0.5; depending on whether or not you included the potassium you could come to the conclusion that either there is a minor contribution from NAGMA, or that the contribution is substantial. Either way, the delta ratio points to a mixed acidosis. The lactate on its own certainly does not explain all of the base deficit.

Thus:

  • There is a mixed respiratory and metabolic acidosis
  • The metabolic acidosis is a mixed high and normal anion gap acidosis
  • There is also hyperglycaemia

Explanations? "Potential reasons for each"?

  • The respiratory acidosis is due to the failure of CO2 clearance associated with severe asthma
  • The A-a gradient is raised- this could be due to increased shunt resulting from a high intrinsic PEEP, or there may be pneumonia.
  • The lactate component of the acidosis is likely due to salbutamol administration
  • The hyperglycaemia is another phenomenon associated with β2-adrenoceptor stimulation (Dawson et al, 1995)
  • The hyperchloraemia is likely due to normal saline resuscitation or the reverse chloride shift which occurs in the arterial circulation (where chloride moves out of RBCs in exchange for bicarbonate)

References

Dawson, K. P., A. C. Penna, and P. Manglick. "Acute asthma, salbutamol and hyperglycaemia.Acta Paediatrica 84.3 (1995): 305-307.

Westen, Edward A., and Henry D. Prange. "A reexamination of the mechanisms underlying the arteriovenous chloride shift." Physiological and Biochemical Zoology 76.5 (2003): 603-614.

Question 12.3 - 2018, Paper 1

a) Describe the acid base abnormalities in the following results and suggest a possible cause.

(20% marks)

Parameter

Patient Value

Adult Normal Range

Fi02

0.5

pH

7.37

7.35 - 7.45

P02

90 mmHa (12 kPa)

PC02

25.0 mmHg (3.6

35 . 0- 45.0 

sp02

Bicarbonate

14.0 mmol/L*

22.0 - 26.0

Base Excess

-10.0 mmol/L*

Lactate

Sodium

1.2 mmol/L

145 mmol/L

135 - 145

Potassium 

4.2 mmol/L

Chloride

93 mmol/L*

95 - 105

Glucose

5.0 mmol/L

College answer

a) 
Metabolic acidosis 
Concomitant respiratory alkalosis  
Elevated anion gap 
Delta ratio 2.6 – concomitant metabolic alkalosis 
 
Salicylate toxicity

Sepsis with vomiting/pain

Any other plausible. 
 

Discussion

Another disembodied gas, not even a stumpy end of a clinical setting. 

To approach this systematically:

  1. We weren't asked about the oxygenation ("describe the acid base abnormalities" they asked) and  so it would attract no marks to point out that there is a substantial A-a gradient (235, a P/F ratio of 180). 
  2. There is a normal pH
  3. There is a metabolic acidosis with a base deficit of -10. The expected CO2 is actually 30 (or 29 by the Boston rules); therefore there is also a respiratory alkalosis
  4. The anion gap is (145+4.2) - (93+14) = 42.2; or 38 sans potassium. Whichever rules you use, clearly there's an anion gap problem.

And so the SAQ unravels  with a tedious inevitability. What could give rise to a high anion gap without much of an acidosis?  For 20% of a 10-mark SAQ, you are only expected to give one differential ("suggest a possible cause", they asked).  The patient is also a bit hypoxic, so - with some stretch of  the imagination - one could generate a multiple myeloma scenario where there is renal failure with some fluid overload and pulmonary oedema, and  the additional anions are accounted for by a raised phosphate and paraprotein. Any other plausible. A reader has submitted euglycaemic DKA as a completely sensible alternative (Rawla et al, 2017)

References

Rawla, Prashanth, et al. "Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma." Endocrinology, diabetes & metabolism case reports 2017.1 (2017).

Question 7.1 - 2018, Paper 2

The following arterial blood gas results are from a 72-year-old male admitted for investigation of nausea, vomiting and severe abdominal pain. He has a history of type 2 diabetes and atrial fibrillation. 


a)    Comment on the abnormalities on this arterial blood gas.               (15% marks) 
 
b)    List five likely causes for the acid-base disturbance.                  (15% marks) 

Parameter

Patient Value

Adult Normal Range

FiO2

0.6

pH

6.98*

7.35 – 7.45

pO2  

92 mmHg  (12.3 kPa)

pCO2

31.0 mmHg (4.1 kPa)*

35.0 – 45.0 (4.6 – 6.0)

SpO2

99%

Bicarbonate 

7.0 mmol/L*

22.0 – 26.0 

Base Excess 

-22.0 mmol/L*

-2.0 – +2.0 

Lactate 

14.5 mmol/L*

0.5 – 1.6

Sodium 

146 mmol/L*

135 – 145 

Potassium 

5.3 mmol/L*

3.5 – 5.0

Chloride 

103 mmol/L

95 – 105

Glucose 

7.7 mmol/L*

3.5 – 6.0

Creatinine

711 μmol/L*

60 – 110

Haemoglobin

108 g/L*

135 – 180

College answer

a) 
Elevated Aa gradient 
Profound lactic acidosis 
High Anion Gap Metabolic Acidosis (36)  
Associated respiratory acidosis or incomplete compensation  
Delta ratio 1.41 – suggests pure elevated anion gap acidosis 
Renal impairment  
 
b) 

Metformin induced 
Ischaemic gut 
Pancreatitis 
Sepsis 
Cardiogenic shock 

Discussion

Let us dissect these results systematically:

  • The A-a gradient is raised (the expected alveolar O2 concentration is = (0.6 × 713) - (3 ×0.8) = 389, so the A-a gradient must be around 297) 
  • There is acidaemia.
  • There is a metabolic acidosis (SBE is -22). Lactate is responsible for virtually all of  it (lactate is 14 mmol/L)
  • The CO2 is appropriately decreased, but not enough. The expected CO2 for "full compensation" would be 28 mmHg by the Copenhagen rules or (7 × 1.5) +8 = 18.5 mmHg by Winter's rule. Thus, there is also a respiratory acidosis
  • The anion gap is raised; it is 36 if you omit potassium and 41.3 if you include it (the consequences of using different equations for this are discussed elsewhere).
  • Assuming an albumin value of 40g/L, the delta ratio is either 1.41 or 1.72, but either way there is a pure HAGMA.
  • Urea is not available, but the creatinine of over 700 strongly suggests that something is wrong with the kidneys.

The college answer gives up only five causes, so one would be expected to at least include these in their list. Here they are again with justifications:

  • Ischaemic gut (AF, nausea, vomiting, abdominal pain)
  • Sepsis (safe differential for everything)
  • Pancreatitis (abdominal pain)
  • Cardiogenic shock (diabetic, AF suggests structural cardiac disease)
  • Metformin (diabetic, therefore presumably on metformin)

Other unofficial possibilities include:

  • Portal vein thrombosis with ascites and hepatorenal syndrome (explains lactate, abdominal pain, and to some extent the creatinine)
  • Malignancy (eg. perforated colorectal cancer with bowel obstruction, which explains everything)

References

Question 9.1 - 2018, Paper 2

A 60-year-old male was admitted after an argument with his partner who found him, 2 hours later, unconscious in his workshop, having likely ingested an unknown substance with empty liquid bottles around him.

 a) Describe the significant abnormalities in the results below.                                                         (20% marks)

Parameter

Patient Value

Adult Normal Range

FiO2

1.0

pH

7.04*

7.35 – 7.45

pO2  

452 mmHg (60.3 kPa)

pCO2

38.0 mmHg (5.07 kPa)

35.0 – 45.0 (4.60 – 6.00)

SpO2

95%

Bicarbonate 

10.0 mmol/L*

22.0 – 26.0 

Base Excess 

-18.0 mmol/L*

-2.0 – +2.0 

Lactate 

15.0 mmol/L*

0.5 – 1.6

Sodium 

141 mmol/L

135 – 145

Potassium  

2.9 mmol/L*

3.5 – 5.0

Chloride 

99 mmol/L

95 – 105

Bicarbonate 

10.0 mmol/L*

22.0 – 26.0 

Glucose 

22.4 mmol/L*

3.5 – 6.0

Urea 

4.7 mmol/L

3.0 – 8.0

Creatinine  

97 μmol/L*

45 – 90 

Magnesium

1.10 mmol/L*

0.75 – 0.95

Albumin 

44 g/L

35 – 50 

Protein 

66 g/L

60 – 80

Total bilirubin 

7 μmol/L

< 26

Aspartate aminotransferase (AST)

98 U/L*

< 35

Alanine aminotransferase (ALT)

20 U/L

< 35

Alkaline phosphatase (ALP)

65 U/L

30 – 110

γ-Glutamyl transferase (GGT)

113 U/L*

< 40

Calcium corrected 

2.08 mmol/L*

2.12 – 2.62

Phosphate 

1.78 mmol/L*

0.80 – 1.50

Creatinine Kinase 

66 U/L

55 – 170 

Osmolality

382 mOsm/kg*

275 – 295

College answer

a) Describe the significant abnormalities in the results. (2 marks) 
(a)    Elevated A-a Gradient (214mmHg) 
(b)    HAGMA 
(c)    Respiratory acidosis (or incomplete compensation) 
(d)    Delta ratio 1.4 (uncomplicated HAGMA) 
(e)    Lactic Acidosis 
(f)    High Osmolar Gap (65) 
(g)    Hyperglycaemia 
(h)    Hypokalemia 
 

Examiners Comments: 
 
Generally, these questions were answered well. Those candidates that failed, missed all or part of the question or misinterpreted what was being asked, reiterating how important it is to read the question and understand what is required before starting to answer. 

 

Discussion

This is another one of the dying breed of CICM PArt II SAQs which ask the trainees to detect a list of abnormalities, which are easy to mark but which unfortunately do not test any sort of higher order analytic skills.

Let us dissect these results systematically:

1) There is an elevated A-a gradient: (1.0  × 713) - (38 / 0.8) - 452 = 213.5 mmHg. The patient is generally hyperoxic (i.e. it is not clear that they need all of that FiO2

2) There is profound acidaemia

3) There is a metabolic acidosis - the SBE is -18

4) There is no respiratory compensation; the expected PaCO2 is (1.5 × 10) + 8 = 23 mmHg, or 22 mmHg by using the Copenhagen SBE-based method of assessing compensation. The upshot of this is that there is a co-existing respiratory acidosis

5) The anion gap is raised (34.9 if you include potassium, 32 if you don't) -  the raised lactate of 15 mmol/L does not explain all of  this gap.

6) The delta ratio is 1.4, which suggests that there is a pure high anion gap acidosis

7) The osmolar gap is raised: calculated osmolality is  (2 × 141 + 22.4 + 4.7) = 309.1, whereas the measured osmolality is 382. The osmolar gap is therefore 73.9 cOsm/kg. The college quote a slightly different value, perhaps because of using a different formula for calculated osmolality. If one includes potassium, the value is closer to the college answer (67.1). Nitpicking aside, it's raised. 

8) Notable abnormalities include:

  • Hypokalemia
  • Hyperglycaemia
  • High albumin (suggesting dehydration)
  • Trivial LFT derangement (GGT)
  • Hypocalcemia
  • Hyperphosphataemia

9) Notable "normalities" include normal renal function, normal CK and essentially normal LFTs.

A nice way to continue this question into the direction of actually testing something meaningful would have been to then ask the trainees, "what three possible causes could have given rise to this biochemical pattern".

References

Question 12 - 2018, Paper 2

List the causes of an elevated lactate immediately following an aortic valve replacement procedure.  
 
Outline your approach to determining the cause. 

College answer

Causes:

Pre- operative drug therapy: - metformin, linezolid, anti-retroviral therapy

Prolonged bypass time

Lactate containing priming solution

Inadequate bypass flow rates

Prolonged hypothermia

Low cardiac output post-surgery – 

Tamponade, 

Myocardial ischaemia/infarction, 

Inadequate replacement valve function

Splanchic ischaemia

Hepatic insufficiency

High dose inotrope therapy

Measurement error

Ischaemic muscle/rhabdomyolysis

Thiamine deficiency

Determining cause

History:

          Review patients comorbidities, and drug history

          History of liver disease or alcohol/malnutrition

          Review course of procedure including bypass time and any complications

Examination

          Current infusions, including beta agonists

          Evidence of poor cardiac output

          Temperature

          Evidence of bleeding – drain losses

Evidence of tamponade – CVP, urine output, drains

          Abdominal examination for gut ischaemia

          Signs of liver failure

          Compartments for signs of muscle ischemia

Investigations

Confirm measurement with repeat

Standard haematology, coagulation and biochemistry tests including creatinine kinase – specifically for evidence of bleeding or liver failure

CXR – evidence of bleeding

ECHO if suspicion of tamponade/valve failure

CT /USS abdomen if suspicion of gut ischaemia/hepatic failure Red cell transketolase if thiamine deficiency suspected

Examiner Comments:

Many candidates provided a general list of causes of hyperlactataemia without being specific to immediately following an aortic valve replacement. When outlining an approach to diagnosing the cause of the elevated lactate, some candidates instead outlined an approach to managing the patient

Discussion

Among the questions which demand a mindless regurgitation of the Cohen-Woods classification of lactic acidosis, this CICM SAQ shines brightest because it then goes on to stress the higher cognitive functions of the candidates with some analysis and interpretation. The aortic valve replacement patient could have a raised lactate for a thousand reasons.

The examiner comments warn against producing a "general list of causes of hyperlactataemia",  but if they then go on to include things like thiamine deficiency and lactated priming solution in their model answer, then surely anything is permitted and no stretch of the imagination is too tenuous. Maybe this patient has HIV, was getting the valve replaced because of syphilitic aortitis, and the lactate is raised because of the effect of antiretroviral drugs. In view of this, a general list of causes is offered here, of which some are more related to a recent AVR than others. (In the colleges' defence, the bypass circuit does cause depletion of thiamine levels).

Increased rate of glycolysis due to lack of ATP

Increased rate of glycolysis due to exogenous pro-glycolytic stimulus

Pyruvate dehydrogenase inactivity

Defects of oxidative phosphorylation

Decreased lactate clearance

With regards to the investigations for this problem, the college answer is actually quite good, and little can be done to improve on it. One may merely reorganise it into some different shape. Thus:

Urgent ABCs:

  • A) Confirm that the airway is well-placed and hypoxia is not being caused by tube kinking or dislodgement
  • B) Ensure oxygenation is satisfactory and ventilation is unaffected:
    • Check the patient (pneumothorax, haemothorax)
    • Check the ventilator (make sure it is connected to gas, and that the waveforms suggest correct ventilation)
    • CXR to confirm auscultation findings
  • C) Assess circulation:
    • Infusions: excessive catecholamines? Catastrophic shock?
    • Adequacy of perfusion of the extremities (palpation, inspection)
    • Adequacy of preload: CVP, PAOP, any evidence of tamponade on TTE
    • Signs of fluid responsiveness (eg. arterial line reverse pulsus paradoxus)
    • Adequacy of cardiac contractility (TTE, cardiac index measurement)
    • Adequacy of valve function (TTE, auscultation - looking for torrential paravalvular leak)
    • Adequacy of graft perfusion (ECG)
  • D) Neurological causes:
    • Assess toxic effects of sedation
      • Propofol dose
      • Paracetamol dose 
    • Exclude seizures through history and examination
  • E) Repeat electrolytes
    • Confirm lactic acidosis is not a measurement error
    • Send red cell transketolase to exclude thiamine deficiency
    • Ensure ionised hypocalcemia is not contributing to shock state
  • F) Assess renal function
    • Exclude rhabdomyolysis - examine muscle compartments and check CK level
    • Ensure there is urine output (aortic dissection or embolic phenomena?)
  • G) Assess hepatic function
    • Exclude pre-exisitng liver disease through history and examination
    • Exclude new onset of liver dysfunction by LFTs and ultrasound
  • H) Exclude anaemia/ blood loss 
    • Coags, FBC, fibrinogen level
  • I) Consider infectious causes
    • Explore infection history and examine for features of infective endocarditis
    • Investigate history for HIV (NRTIs) tuberculosis (isoniazid) or malignancy.
    • Culture blood, urine, sputum

References

Narins RG, Krishna GG, Yee J, Idemiyashiro D, Schmidt RJ: The metabolic acidoses. In: Maxwell & Kleeman's Clinical Disorders of Fluid and Electrolyte Metabolism, edited by Narins RG, New York, McGraw-Hill, 1994, pp769 -825

Luft FC. Lactic acidosis update for critical care clinicians. J Am Soc Nephrol 2001 Feb; 12 Suppl 17 S15-9.

Ohs manual – Chapter 15 by D J (Jamie) Cooper and Alistair D Nichol, titled “Lactic acidosis” (pp. 145)

Cohen RD, Woods HF. Lactic acidosis revisited. Diabetes 1983; 32: 181–91.

Reichard, George A., et al. "Quantitative estimation of the Cori cycle in the human." Journal of Biological Chemistry 238.2 (1963): 495-501.

Andres, Reubin, Gordon Cader, and Kenneth L. Zierler. "The quantitatively minor role of carbohydrate in oxidative metabolism by skeletal muscle in intact man in the basal state. Measurements of oxygen and glucose uptake and carbon dioxide and lactate production in the forearm." Journal of Clinical Investigation 35.6 (1956): 671.

Phypers, Barrie, and JM Tom Pierce. "Lactate physiology in health and disease." Continuing Education in Anaesthesia, Critical Care & Pain 6.3 (2006): 128-132.

Donnino, Michael W., et al. "Coronary artery bypass graft surgery depletes plasma thiamine levels." Nutrition 26.1 (2010): 133-136.

Question 18.1 - 2018, Paper 2

A previously well 23-year-old male has been an inpatient on your ICU for six days following an isolated traumatic brain injury. He has been extremely agitated and required constant infusions of propofol and fentanyl. A full workup has confirmed there are no other injuries, and he has been stable from a haemodynamic, respiratory and metabolic standpoint since admission. This morning he has become hypotensive, and the following results are available. 

  1. List the significant abnormalities.                                                               (30% marks)
  2. What is the likeliest diagnosis?                                                                  (10% marks)

Parameter

Patient Value

Adult Normal Range

FiO2

0.4

pH

7.16*

7.35 – 7.45

pO2  

120 mmHg (16 kPa)

pCO2

35.0 mmHg (4.7 kPa)

35.0 – 45.0 (4.6 – 6.0)

SpO2

97%

Bicarbonate 

12.0 mmol/L*

22.0 – 26.0 

Base Excess 

-15 mmol/L*

-2.0 – +2.0 

Lactate 

9.2 mmol/L*

0.5 – 1.6

Sodium 

145 mmol/L

135 – 145

Potassium  

6.3 mmol/L*

3.5 – 5.0

Chloride 

98 mmol/L

95 – 105

Bicarbonate 

12.0 mmol/L*

22.0 – 26.0 

Glucose 

10.2 mmol/L*

3.5 – 6.0

Urea 

6.7 mmol/L

3.0 – 8.0

Creatinine  

70 μmol/L

45 – 90 

Creatinine Kinase 

43,500 U/L*

55 – 170 

College answer

a) 
High anion gap metabolic acidosis 
Associated respiratory acidosis 
Delta ratio 1.9 suggesting pure HAGMA 
Elevated Aa gradient 
Rhabdomyolysis 
 
b) 
Diagnosis: 
Propofol Infusion Syndrome 

      

Discussion

To approach this systematically:

1) The A-a gradient is raised;  (0.4 × 713) - (35 / 0.8) - 120 = 121.5 mmHg.

2) There is severe acidaemia.

3) There is a severe metabolic acidosis (SBE is -15)

4) There is minimal effort at respiratory compensation - the expected CO2 is  25 mmHg by the Copenhagen SBE rules, or 26 using Winter's rule where expected CO2 = (1.5 ×12)+ 8. Thus, there is also a respiratory acidosis.

5) The anion gap is elevated; it is 35 if you omit potassium from the equation, or 41.3 if you do not. The delta ratio therefore also changes. Assuming a normal albumin of 40g/L, the delta ratio is either 2.4 (with potassium) or 1.9 (without). Thus, depending on whether or not you include that electrolyte in your anion gap equation, you'd either develop the impression that there is a co-existing metabolic alkalosis, or that this is a pure HAGMA. The evils of the anion gap and whether or not one ought to involve the potassium ions are debated elsewhere.

Other abnormalities which can be seen:

  • High lactate 
  • Rhabdomyolysis

The diagnosis of propofol infusion syndrome is suggested by the story, where this young man is pickled in propofol for some days following his traumatic brain injury. Other features of PRIS are :

  •     Acute bradycardia leading to asystole.
    • A prelude to the bradycardia is a sudden onset RBBB with ST elevation in V1-V3; Kam’s article has the picture of this ECG. 
  •     Arrhythmias    
  •     Heart failure, cardiogenic shock
  •     Metabolic acidosis (HAGMA) with raised lactate (and also due to fatty acids)
  •     Rhabdomyolysis
  •     Hyperlipidaemia
  •     Fatty liver and hepatomegaly
  •     Coagulpathy
  •     Raised plasma malonylcarnitine and C5-acylcarnitine

References

 Underwood, Ao H., and E. A. Newsholme. "Properties of phosphofructokinase from rat liver and their relation to the control of glycolysis and gluconeogenesis." Biochemical Journal 95.3 (1965): 868.

Kam, P. C. A., and D. Cardone. "Propofol infusion syndrome." Anaesthesia62.7 (2007): 690-701.

Marinella, Mark A. "Lactic acidosis associated with propofol." CHEST Journal109.1 (1996): 292-292.

Vasile, Beatrice, et al. "The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome." Intensive care medicine 29.9 (2003): 1417-1425.

Schenkman KA, Yan S. Propofol impairment of mitochondrial respiration in isolated perfused guinea pig hearts determined by reflectance spectroscopy. Critical Care Medicine 2000; 28: 172–7.

Question 18.3 - 2018, Paper 2

A 28-year-old female has presented with a severe asthma attack. She is 26 weeks pregnant. 

        a) Comment on her arterial blood gas result shown below.                                                           (40% marks)

Parameter

Patient Value

Adult Normal Range

FiO2

0.6

pH

7.31*

7.35 – 7.45

pO2 

120 mmHg (16 kPa)

pCO2

42.0 mmHg (5.6 kPa)

35.0 – 45.0 (4.6 – 6.0)

SpO2

98%

Bicarbonate 

20.0 mmol/L*

22.0 – 26.0 

Base Excess 

-4.9 mmol/L*

-2.0 – +2.0 

Lactate 

3.0 mmol/L*

0.5 – 1.6

Sodium 

136 mmol/L

135 – 145 

Potassium 

3.2 mmol/L*

3.5 – 5.0

Chloride 

105 mmol/L

95 – 105

Glucose 

8.1 mmol/L*

3.5 – 6.0

College answer

a) 

Respiratory acidosis 
Metabolic acidosis 
Normal anion gap High A-a gradient 
Suggests imminent fatigue, as CO2 should be lower in pregnancy. The reduced bicarbonate may indicate chronic compensation for preexisting respiratory alkalosis of pregnancy. 
The elevated lactate and glucose are likely secondary to B2 agonist treatment and stress response. 
 

Discussion

"Comment on her arterial gas result shown below" is a curious choice of SAQ wording, and certainly the (usually essay-related) instruction word  "comment" is not a part of the standard repertoire of CICM SAQ stems (for example, it does not appear in the glossary of terms at the front of the paper). That violation of SAQ design is probably forgivable because the candidates (being intelligent people) would have done past papers before, and will have worked out quickly that the CICM examiners really just wanted them to interpret the results and list the abnormalities.

Thus, in a systematic fashion:

1) There is a widened A-a gradient. The gradient is  (0.6  × 713) - (42 / 0.8) - 120 = 255.3 mmHg

2) There is mild acidaemia

3) There is a mild metabolic acidosis (SBE -4.9)

4) The respiratory compensation in non-existent, as the CO2 in pregnancy is expected to be lower. For a non-pregnant patient, the CO2 should be 35.1 mmHg by the SBE method, or 38 mmHg by Winter's rule. In short, there is respiratory acidosis. 

5) The anion gap calculated with potassium is 14.2, or 11 without it. In other words, it is essentially normal, insofar as it would be embarrassing to try to calculate the delta ratio.

6) Other abnormalities are well explained by the (no doubt continuous) salbutamol.

The salient feature pointed out by the college here is the respiratory acidosis, which- no matter pregnant or not - is a bad sign in severe acute asthma.

References

Question 3.1 - 2019, Paper 1

A 69-year-old female with a past history of multiple bowel surgeries and severe rheumatoid arthritis presents to the ICU with hypotension. The following results are obtained:

Parameter

Patient Value

Adult Normal Range

FiO2

0.30

pH

7.36

7.35 – 7.45

pO2

79.7 mmHg (10.6 kPa)

pCO2

22.0 mmHg (2.9 kPa)*

35.0 – 45.0 (4.6 – 6.0)

SpO2

96.1%

Bicarbonate

12.0 mmol/L*

22.0 – 26.0

Base Excess

-12.0 mmol/L*

-2.0 – +2.0

Lactate

3.9 mmol/L*

0.5 – 1.6

Sodium

133 mmol/L*

135 – 145

Potassium

5.3 mmol/L*

3.5 – 5.0

Chloride

109 mmol/L*

95 – 105

Glucose

4.1 mmol/L

3.5 – 6.0

  1. Describe the acid base abnormality.   (10% marks)
  2. Give three potential causes for this patient’s hypotension consistent with these results. Provide a rationale for each cause.    (30% marks)

College answer

Describe the acid base abnormality: (10% marks)

Normal anion gap metabolic acidosis and respiratory alkalosis

Give three potential causes for this patient’s hypotension consistent with this ABG. Provide a rationale for each cause. (30% marks)

  1. Addisonian crisis. Hypotension, normal anion gap acidosis, high potassium and low sodium all fit. Patient likely to be on long term steroid treatment for rheumatoid making her vulnerable to this condition. (Note: if this was secondary adrenal insufficiency the potassium would not normally be raised; )
  2. Hypovolemia from fistula – Na consistent, and history of bowel surgery suggestive. Again, would expect a non-anion gap acidosis.
  3. Hypovolemia from diarrhoea: patients history makes her vulnerable to infective causes especially. NAGMA fits.

Coexistent respiratory alkalosis likely to be secondary to hyperventilation from pain/distress (any other plausible explanation acceptable – note candidates not required to comment on this)

Examiners Comments:

Some candidates paid insufficient attention to the clinical information in the stem, leading to generic responses and inappropriate prioritisation of information. Some failed to list potential causes of hypotension consistent with the ABG and lost potentially easy marks as a result of not slowing down and reading the question.
 

Discussion

Let us dissect these data;

  • The A-a gradient is raised:  (0.3 x 713) - (22.0 x 1.25) - 79.7 = 106.7 mmHg
  • There is acidaemia
  • There is a metabolic acidosis (SBE = -12)
  • The CO2 is lower than it should be: the expected value is 28 mmHg (using the SBE method) or 26 mmH (using Winter's formula).
  • The anion gap is (133  + 5.3 ) - (109  + 12.0) = 17.3, or 12 when calculated sans potassium. Considering the college answer is NAGMA, we can assume they also omitted potassium in their calculation and used the older value range for the anion gap. 

Thus: this is a metabolic acidosis, which is either completely or almost completely a normal anion gap phenomenon, with some respiratory alkalosis. The college suggests that this alkalosis may be due to pain or distress, which is plausible. There is an A-a gradient but the patient is not particularly hypoxaemic, i.e. hypoxia is not driving this tachypnoea.

Potential causes for this patient’s hypotension:

The college suggestions make sense, and the college answer is well-reasoned: 

  • Addisonian crisis
  • Hypovolemia from fistula 
  • Hypovolemia from diarrhoea

An alternative suggestion could be basic bog-standard sepsis of abdominal origin. The raised lactate, suggestive history, impaired immunity - these raise sepsis as a possibility. Being resuscitated with saline in the ward would account for the hyperchloraemia.

References

Question 3.2 - 2019, Paper 1

An 84-year-old male with a recent diagnosis of myeloma and osteoarthritis is admitted to ICU following a three-day history of constipation followed by diarrhoea.

Parameter

Patient Value

Adult Normal Range

FiO2

0.21

pH

7.22*

7.35 – 7.45

pO2

98 mmHg (13 kPa)

pCO2

10.0 mmHg (1.3 kPa)*

35.0 – 45.0 (4.6 – 6.0)

SpO2

99.6%

Bicarbonate

4.0 mmol/L*

22.0 – 26.0

Base Excess

-22.0 mmol/L*

-2.0 – +2.0

Lactate

1.4 mmol/L

0.5 – 1.6

Sodium

133 mmol/L*

135 – 145

Potassium

5.7 mmol/L*

3.5 – 5.0

Chloride

113 mmol/L*

95 – 105

Glucose

4.4 mmol/L

3.5 – 6.0

a)    Describe the acid base abnormality.    (10% marks)

b)    Give a physiological rationale for the acid base abnormalities in this patient.
(20% marks)
 

College answer

Describe the acid base abnormality. (10% marks)

High anion gap metabolic acidosis, respiratory alkalosis, delta ratio of 0.2 suggesting associated normal anion gap metabolic acidosis.

Give a physiological rationale for the acid base abnormalities in this patient (20% marks)

HAGMA without elevated lactate in this scenario may be renal failure (multiple possible causes) or starvation ketosis

Coexisting NAGMA from diarrhoea

Respiratory alkalosis from hyperventilation secondary to pain/distress

Only one rationale per abnormality required.

Discussion

Let us dissect these data;

  • The A-a gradient is close to zero. 
  • There is acidaemia
  • There is a metabolic acidosis (SBE = -22)
  • The CO2 is lower than it should be: the expected value is 18 mmHg (using the SBE method) or 14 mmH (using Winter's formula).
  • The anion gap is (133  + 5.7 ) - (113  + 4.0) = 21.7, or 16 when calculated sans potassium.
  • The delta ratio is (21.7-12)/(24-4.0) = 0.49, or 0.2 if older values are used (where the standard anion gap value is 12, and the gap is calculated without potassium). 

This is weird. Irrespective of which formula you use, the delta ratio range associated with a mixed disturbance is probably 0.4-0.8 (according to Brandis), as the older  0.8-1.2  range had poorer sensitivity (according to Rastegar, 2007). Either way, delta ratio of 0.2 is not expected to be associated with a mixed disorder. Taken literally, this value suggests that the rise in the anion gap accounts for only 20% of the drop in the bicarbonate. Using updated values and incorporating the nontrivial potassium (5.7mmol/L) one arrives at a delta ratio of 0.5 or so, which is more consistent with a mixed disturbance. 

Physiological rationale for the acid base abnormalities in this patient:

There are multiple possible causes for a mixed distrubance. Individually, the causes of metabolic acidosis are: 

High anion gap

Normal anion gap

MUD PILES

PANDA RUSH

This old man with constipation and diarrhoea could potentially have any number of these causes, considering that we have zero history. Renal failure is a plausible cause of this acid-base disturbance because the acidosis is usually mixed in that setting, and the history suggests some fluid depletion.  

References

Rastegar, Asghar. "Use of the ΔAG/ΔHCO3− Ratio in the Diagnosis of Mixed Acid-Base Disorders." Journal of the American Society of Nephrology 18.9 (2007): 2429-2431.

Dinubile, MarkJ. "The increment in the anion gap: overextension of a concept?." The Lancet 332.8617 (1988): 951-953.

Question 3.3 - 2019, Paper 1

A 44-year-old female, who is a type II diabetic, has been fasting for elective morning surgery. She is currently on oral anti-diabetic drugs.

On admission to the day surgery unit, she describes feeling nauseous with diffuse abdominal pain. The following results are obtained:

Parameter

Patient Value

Adult Normal Range

FiO2

0.21

pH

7.28*

7.35 – 7.45

pO2

102 mmHg (13.6 kPa)

pCO2

40.0 mmHg (5.3 kPa)

35.0 – 45.0 (4.6 – 6.0)

SpO2

97%

Bicarbonate

18.0 mmol/L*

22.0 – 26.0

Base Excess

-8.0 mmol/L*

-2.0 – +2.0

Sodium

141 mmol/L

135 – 145

Potassium

3.6 mmol/L

3.5 – 5.0

Chloride

103 mmol/L

95 – 105

Glucose

6.0 mmol/L

3.5 – 6.0

Ketones

5 mg/L*

< 1

  1. Comment on the acid base status. (10% marks)
  1. List three potential causes of the elevated ketone level in this patient. (20% marks

College answer

a)    Comment on the acid base status.    (10% Mark)
High AG metabolic acidosis
Secondary respiratory acidosis

b)    List three potential causes of the elevated ketone level in this patient? (20% mark)
1.    SGLT2 Inhibitor
2.    Starvation
3.    Alcohol
 

(Note to examiners – diabetic ketoacidosis not accepted unless described as adverse effect of the SGLT2 inhibitor.)

Examiners Comments:

Some candidates paid insufficient attention to the clinical information in the stem, leading to generic responses and inappropriate prioritisation of information. Some failed to list potential causes of hypotension consistent with the ABG and lost potentially easy marks as a result of not slowing down and reading the question.
 

Discussion

"Comment on the acid base status" they asked. The college's "GLOSSARY OF TERMS" from the beginning of the paper does not contain a specific description of the term "comment". The common language definition, "to express an opinion about something", may not be appropriate, as one's opinion of the acid base status may be "it's fucked".  

Anyway, let's assume they wanted us to intrpret the ABG result:

  • The A-a gradient is close to zero. 
  • There is a mild acidaemia
  • There is a mild metabolic acidosis (SBE = -8)
  • The CO2 is higher than it should be: the expected value is 32 mmHg (using the SBE method) or 35 mmH (using Winter's formula). Thus, there is a coexisting (mild) respiratory acidosis.
  • The anion gap is (141 + 3.6) - (103  + 18) = 23.6, or 20 when calculated sans potassium.
  • The delta ratio is (23.6-12)/(24-18) = 1.93, or 1.3 if older values are used (where the standard anion gap value is 12, and the gap is calculated without potassium). Regardless of which formula you subscribe to, the ratio suggests that this is a pure HAGMA. 

List three potential causes of the elevated ketone level in this patient:

The combiation of ketoacidosis, normal glucose and the history of being a Type 2 diabetic on "oral anti-diabetic drugs" is stronly suggestive of SGLT2 inhibitor effects. This sort of ketoacidosis is classically euglycaemic (Rosenstock et al, 2015). Other causes of ketoacidosis can be suggested to explain these findings on the basis of an excellent article by Davids et al 92004), which, though highly informative, is unfortunately written using an imaginary ward round  as a narrative device.

Anyway, the causes:

  • Diabetic ketoacidosis following the commencement of insulin therapy
  • Alcoholic ketoacidosis 
  • Starvation ketoacidosis due to fasting for eletive surgery
  • Inhibition of of insulin release  (α-adrenergic agents and diazoxide) 
  • Acetate excess (eg. unregulated nonglucose carbohydrate excess)
  • Inhibition of acetyl-CoA carboxylase (eg. by firsocostat)

References

Rosenstock, Julio, and Ele Ferrannini. "Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors." Diabetes care 38.9 (2015): 1638-1642.

Davids, M. R., et al. "An unusual cause for ketoacidosis.Qjm97.6 (2004): 365-376.

Question 18.1 - 2019, Paper 1

A 76-year-old male with a background of emphysema is now Day 7 after an elective colectomy. His ICU stay was complicated by intra-abdominal sepsis and ongoing high-volume nasogastric aspirates. There is difficulty in weaning him from the ventilator. The following arterial blood gases are obtained:

Parameter

Patient Value

Adult Normal Range

FiO2

0.35

pH

7.58*

7.35 – 7.45

pO2

82.0 mmHg (10.9 kPa)

pCO2

52.0 mmHg (6.9 kPa)*

35.0 – 45.0 (4.6 – 6.0)

SpO2

94%

Bicarbonate

47.0 mmol/L*

22.0 – 26.0

Base Excess

23.7 mmol/L*

-2.0 – +2.0

  1. Describe the acid-base disturbance. (10% marks)
  2. List three likely causes. (15%marks)

College answer

a)    There is a primary metabolic alkalosis which is appropriately compensated.

b)    Likely causes
1.    Volume depletion due to high naso-gastric losses causing contraction alkalosis
2.    Any cause of hyperaldosteronism (e.g., Glucocorticoids for emphysema, Barrter’s syndrome, Cushing’s disease etc)
3.    Chloride loss in urine from diuretics; e.g. frusemide
 

Discussion

Let us dissect these results systematically:

1)  The A-a gradient is significantly increased:
(0.35 x 713) - (52 x 1.25) - 82 = 102.55 mmHg

2) There is an alkalaemia

3) The CO2 is appropriately elevated

4)  There is a metabolic alkalosis (the SBE is 23.7)

5) The respiratory compensation is appropriate:  (0.7 × 47) + 20 = 52.9 mmHg, or (0.6  × 23.7) + 40 = 54.22 mmHg, depending on which formula you use.  

Causes of metabolic alkalosis in this case could include a broad range of differentials, but the question text clearly describes a man who is losing chloride constantly from the NG tube and whose COPD history predisposes him to a compensatory post-hypercapnia alkalosis. One could also safely wager that steroids and frusemide have at some stage been used in their care. For completeness, here is the full list:

Causes of Metabolic Alkalosis; Organised by Inorganic Ion

Anions

Cations

Chloride depletion

  • Gastric losses by vomiting or drainage
  • Diuretics: loop or thiazides
  • Diarrhoea
  • Posthypercapneic state
  • Dietary chloride deprivation
  • Gastrocystoplasty
  • Cystic fibrosis (loss due to high sweat chloride content)

Bicarbonate excess (real or apparent)

  • Iatrogenic alkalinisation
  • Recovery from starvation
  • Hypoalbuminemia

Potassium depletion

  • Primary hyperaldosteronism
  • Mineralocorticoid oversupplementation
  • Licorice (glycyrrhizic acid)
  • β-lactam antibiotics
  • Liddle syndrome
  • Severe hypertension
  • Bartter and Gitelman syndromes
  • Laxative abuse
  • Clay ingestion

Calcium excess

  • Hypercalcemia of malignancy
  • Milk-alkali syndrome

References

Cogan, Martin G. "Chronic hypercapnia stimulates proximal bicarbonate reabsorption in the rat." Journal of Clinical Investigation 74.6 (1984): 1942.

Khanna, Apurv, and Neil A. Kurtzman. "Metabolic alkalosis." studies 28 (2006): 29.

Tripathy, Swagata. "Extreme metabolic alkalosis in intensive care." Indian journal of critical care medicine: peer-reviewed, official publication of Indian Society of Critical Care Medicine 13.4 (2009): 217.

Galla, John H. "Metabolic alkalosis." Journal of the American Society of Nephrology 11.2 (2000): 369-375.

Pahari, D. K., et al. "Diagnosis and management of metabolic alkalosis."JOURNAL-INDIAN MEDICAL ASSOCIATION 104.11 (2006): 630.

Palmer, Biff F., and Robert J. Alpern. "Metabolic alkalosis." Journal of the American Society of Nephrology 8.9 (1997): 1462-1469.

Gennari, F. John. "Pathophysiology of metabolic alkalosis: a new classification based on the centrality of stimulated collecting duct ion transport." American Journal of Kidney Diseases 58.4 (2011): 626-636.

Question 18.2 - 2019, Paper 1

A 28-year-old female presented to the Emergency Department with general malaise. The following results are obtained from blood and urine respectively:

Parameter

Patient Value

Adult Normal Range

Blood Results:

FiO2

0.21

pH

7.29*

7.35 – 7.45

pO2

106 mmHg (14 kPa)

pCO2

26.0 mmHg (3.5 kPa)*

35.0 – 45.0 (4.6 – 6.0)

SpO2

97%

Bicarbonate

12.0 mmol/L*

22.0 – 26.0

Base Excess

-13.0 mmol/L*

-2.0 – +2.0

Sodium

137 mmol/L

135 – 145

Potassium

0.9 mmol/L*

3.5 – 5.0

Chloride

119 mmol/L*

95 – 105

Glucose

8.1 mmol/L*

3.5 – 6.0

Phosphate

0.3 mmol/L*

0.8 – 1.5

Urine Results:

pH

7.50

Sodium

36 mmol/L*

10 – 20

Potassium

37 mmol/L*

5 – 15

Chloride

22 mmol/L

20 – 40

  1. Describe the acid base abnormality on the blood results. (10% marks)
  1. Give three potential causes of these findings with a rationale for your answer.
    (15% marks)

College answer

a)    There is a non-anion gap metabolic acidosis.

b)    Likely causes
1.    Type 1 or 2 Renal Tubular Acidosis (High urinary pH)
2.    Salt wasting nephropathies (high urinary Na)
3.    Diuretic use/abuse (High urinary Na and K, low K and Phos)
4.    Conns (High urinary Na and K, low plasma K)
 

Discussion

Let us dissect these results systematically:

1)  The A-a gradient is essentially normal:
(0.21 x 713) - (26 x 1.25) - 106 = 11.23 mmHg

2) There is an acidaemia, which is mild.

3) The CO2 is appropriately low

4)  There is a metabolic acidosis (the SBE is -13)

5) The respiratory compensation is appropriate:  (1.5 × 12) + 8 = 26 mmHg, or (40 - 13) = 27 mmHg, depending on which formula you use.  

6) The anion gap is (137) - (119 + 12) = 6, or 6.9 when calculated using the absurdly low potassium value. To calculate the delta ratio would therefore be pointless.

7) The urinary anion gap is (36+37) - 22 = 51, i.e. it is a positive urinary anion gap.  This suggests a renal cause of the acidosis. A negative (neGUTive) anion gap would suggest that gastrointestinal causes of NAGMA are in play, as the kidneys are doing their job. However, the combination of low urinary chloride and a urinary pH higher than the serum pH suggests that clearly they are not. 

Additional findings include a low phosphate and a higher than expected glucose.

So, what are the possible renal-related reasons for a NAGMA?

The inclusion of Conn's syndrome, or primary aldosteronism, is somewhat unexpected, as the excess of aldosterone (and therefore the increased activity of sodium-reabsorbing eNaC channels in the collecting duct) is actually expected to cause a decrease in the urinary sodium concentration. So much so in fact that the change in the ratio of serum to urinary sodium has been used as a cheap tool to screen for Conn's syndrome (Willenberg et al, 2009). 

References

Willenberg, H. S., et al. "The serum sodium to urinary sodium to (serum potassium) 2 to urinary potassium (SUSPPUP) ratio in patients with primary aldosteronism.European journal of clinical investigation 39.1 (2009): 43-50.

Kraut, Jeffrey A., and Nicolaos E. Madias. "Metabolic acidosis: pathophysiology, diagnosis and management." Nature Reviews Nephrology 6.5 (2010): 274-285.

Fencl, Vladimir, et al. "Diagnosis of metabolic acid–base disturbances in critically ill patients." American journal of respiratory and critical care medicine162.6 (2000): 2246-2251.

Moviat, M. A. M., F. M. P. Van Haren, and J. G. Van Der Hoeven. "Conventional or physicochemical approach in intensive care unit patients with metabolic acidosis." Critical Care 7.3 (2003): R41.