Outline the causes, and the principles of management of lactic acidosis in the critically ill.
• 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).
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:
Causes of lactic acidosis can be better classified according to the lesser-known (but biochemically superior) Phuypers and Pierce system:
Increased rate of glycolysis due to lack of ATP
Increased rate of glycolysis due to exogenous pro-glycolytic stimulus
Unregulated substrate entry into glycolysis
Pyruvate dehydrogenase inactivity
Defects of oxidative phosphorylation
Decreased lactate clearance
|
The approach to the management of lactic acidosis can be divided into two main approaches:
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.
Outline the way in which you would evaluate the aetiology of metabolic acidosis in the critically ill.
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).
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:
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.
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.
Outline the way in which you would evaluate the aetiology of metabolic alkalosis in the critically ill.
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).
This question closely resembles Question 7 from the first paper of 2008.
Outline your approach to determining the appropriate magnitude of respiratory compensation for a metabolic acidosis and a metabolic alkalosis.
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.
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
Roberts, Kathleen E., et al. "Evaluation of respiratory compensation in metabolic alkalosis." Journal of Clinical Investigation 35.2 (1956): 261.
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.
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).
This is not a pure ABG interpretation question; it required some thinking about the management of severe asthma.
But first, lets interpret the ABG.
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:
Breathing:
Circulation
Oh's Intensive Care manual: Chapter 35 (pp. 401) Acute severe asthma by David V Tuxen and Matthew T Naughton.
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.
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.
Let us dissect these results systematically.
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:
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.
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 |
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.
Let us dissect these results systematically.
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.
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.
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
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
Let us dissect these results systematically.
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:
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:
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.
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.
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
Base excess definition
Standard base excess
"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.
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.
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
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 I Phenformin
- Alcohols
- Cyanide, nitroprusside
- Salicylates
This question is frequently repeated. Notable duplicates include the following:
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.
Discuss the advantages and limitations of the anion gap in the evaluation of acid-base disturbance
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
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
Limitations of the anion gap
A discussion of the anion gap is available locally in two forms: as a quick revision summary and as a massive rambling digression.
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.
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..
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
Let us dissect these results systematically.
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.
Low urinary potassium
High urinary potassium with acidosis
|
High urinary potassium with alkalosis
|
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.
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.
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
Drugs:
1) RTA 1 or 2
2) Ampho B,
3) Acetazolamide
4) GI losses
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:
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:
Story DA. Hyperchloraemic acidosis: another misnomer? Crit Care Resusc. 2004 Sep;6(3):188-92.
List the causes of metabolic alkalosis and explain how you will evaluate a patient with metabolic alkalosis.
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
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.
This flowchart can be converted into the form of a point-form answer:
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
Recent history
Examination
Biochemistry
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.
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.
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.
Let us dissect these results systematically.
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.
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.
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 |
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.
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.
Let us dissect these results systematically.
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:
Sankaran, Ramkumar T., et al. "Laboratory abnormalities in patients with bacterial pneumonia."CHEST Journal 111.3 (1997): 595-600.
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 |
39 mmHg (5.2 kPa) |
35-45 mmHg (4.7-6.0 |
PaO2 |
203 mmHg (33.6 kPa) |
94 mmHg (12.5 kPa) |
75-98 mmHg (10.0- |
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 |
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?
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
This question is identical to Question 15.2 from the second paper of 2009.
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
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
This question is identical to Question 15.3 from the second paper of 2009.
Outline how pH, PCO2 and PO2 are measured in a blood gas analyser and briefly state the underlying principle behind each of those measurements.
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
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:
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.
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?
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.
Let us dissect these results systematically.
Three causes of normal anion gap metabolic acidosis?
The mnemonic PANDA RUSH comes to mind, even though it is not very good.
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.
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.
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.
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.
Let us dissect these results systematically.
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.
Oh, M. S., H. J. Carroll, and J. Uribarri. "Mechanism of normochloremic and hyperchloremic acidosis in diabetic ketoacidosis." Nephron 54.1 (1990): 1-6.
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).
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).
Let us dissect these results systematically.
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 PAO2 of 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.
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 | |
|
|
|
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?
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.
Let us dissect these results systematically.
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.
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.
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.
Drug Anion
Ethanol - Lactate
Methanol - Formate or formic acid
Ethylene glycol - Glycolate / oxalate
Ethanol overindulgeance can indeed cause a lactic acidosis, but I would have chosen a different drug:
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.
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?
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)
Analysis of the biochemistry:
Analysis of the haematology:
Analysis of the ABG:
Causes of the lactic acidosis in this case:
Management priorities:
Something like this benefits from a structured approach.
Airway:
Breathing:
Circulation:
Disability/neurology is not a matter of priority at present.
Electrolyte derangement however is.
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 |
94 mmHg (12.5 |
75 – 98 (10.0-13.0 kPa) |
Actual |
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 |
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?
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
Let us dissect these initial results systematically.
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:
Phypers, Barrie, and JM Tom Pierce. "Lactate physiology in health and disease." Continuing Education in Anaesthesia, Critical Care & Pain 6.3 (2006): 128-132.
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.
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
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.
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.
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
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.
24.1. List the acid-base abnormalities.
24.2. What are the causes of elevated plasma lactate in sepsis?
Copying directly from Question 22.2:
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.
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.
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.
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) |
• 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.
These biochemistry results are provided without any history.
Let us dissect them systematically.
Thus, this high anion gap metabolic acidosis is also associated with a raised osmolar gap.
Most likely differentials:
Less likely differentials (osmolar gap is probably a bit too high for these to be realistic differentials):
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.
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) |
• Raised osmolar gap with normal AG
• Mannitol
• Glycine
• Ethanol
These biochemistry results are provided without any history.
Let us dissect them systematically.
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:
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.
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.
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.
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
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:
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:
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:
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:
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).
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.
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.
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
This question is identical to Question 6.1 from the first paper of 2013.
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.
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
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:
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.
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.
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?
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
This question is identical to Question 6.3 from the first paper of 2013.
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.
a) List the acid-base abnormalities.
Lactic acidosis
Anion gap elevation (37 mEq/L) Metabolic alkalosis
Respiratory alkalosis
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.
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.
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
Let us dissect these results systematically.
The college suggests the following explanations for this gas:
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.
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.
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
a) Interpret these results
Metabolic alkalosis with partial respiratory compensation and severe hypokalaemia
b) List 2 likely diagnoses
c) Give 2 drugs used to treat this condition
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
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.
Chloride depletion
Bicarbonate excess (real or apparent)
|
Potassium depletion
Calcium excess
|
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.
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.
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
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)
Logically, (b) is the question one ought to answer first, in order to answer (a).
Thus: a systematic approach:
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:
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.
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.
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.
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
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)
This is another one of these "interpret an ABG" questions.
How did they arrive at these answers?
Normal osmolar gap
The calculated osmolality is 298.4, from ((2 ×139) + 15.3 + 5.1))
This gives an osmolar gap of 1.6.
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 complete 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.
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.
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?
a)
Metabolic alkalosis
A-a DO2 295
b)
Resolution of respiratory acidosis with delayed correction of metabolic compensation
Diuretic therapy
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.
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.
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?
a) Normal anion gap severe metabolic acidosis with incomplete compensation
b)Renal tubular acidosis Type 1 distal secondary to chronic toluene abuse
How did they reach these conclusions?
Let us approach this systematically.
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.
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
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
a)
Metabolic alkalosis with respiratory compensation
b)
Diuretic therapy
Steroid therapy
Vomiting from gastric outlet obstruction
Post hypercapnoeic alkalosis
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.
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:
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.
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?
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.
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.
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.
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
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
a) Describe the abnormalities on the above arterial blood gas profile
b) List three causes of a raised lactate in sepsis
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) - 28.8 = 185.1, thus the A-a difference is 195.5-107 = 78.1.
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.
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.
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?
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?
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).
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.
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
i.
ii.
This question is a fairly straightforward ABG interpretation exercise.
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.
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.
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 |
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.
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:
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.
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
i.
ii.
Any other reasonable cause
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 PCO2 in 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.
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?
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.
Let us dissect these results systematically.
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:
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:
One would want to stop feeding this man the paracetamol and flucloxacillin.
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
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 |
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.
This question is very similar to Question 6.2 from the first paper of 2013.
Let us dissect these results systematically.
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.
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.
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 |
a)
b)
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.
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 |
a)
b)
Let us dissect these results systematically.
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:
I do not see how listing "death" as a complication earns any marks in this exam.
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.
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 |
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
Let us dissect these results systematically.
The lactate is 13, which can actually account for all of the increase in the anion gap. The anion gap is 23, which means it has increased by 11. The lactate is 13. What other anions do you need here?
Perhaps they want a better explanation for the change in SBE? True, there is a very large base deficit. Taking the simplistic view that lactate is a fully dissociated ion and for every mole of lactic acid there should be a mole of hydrogen ions, one would still fall short of explaining the SBE of -19.
Anyway: why is the lactate so high, the college asks?
Differentials relevant to this case might include the following:
Approaching the management systematically, one might respond to the last question in the following fashion:
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.
For each set of the following biochemical and arterial blood gas parameters:
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) |
Increased anion gap, metabolic alkalosis and respiratory alkalosis.
Clinical scenario – salicylate overdose.
Let us dissect these results systematically.
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.
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.
For each set of the following biochemical and arterial blood gas parameters:
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) |
Increased anion gap metabolic acidosis and metabolic alkalosis.
Clinical scenario – acute renal failure with vomiting .
Let us dissect these results systematically.
Thus, this is a high anion gap metabolic acidosis with a coexisting metabolic alkalosis. Scenarios in which this might arise include the following:
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.
For each set of the following biochemical and arterial blood gas parameters:
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) |
Acute respiratory acidosis with metabolic alkalosis.
Clinical scenario – acute respiratory failure in COAD (Acute on chronic respiratory failure.
Let us dissect these results systematically.
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:
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).
For each set of the following biochemical and arterial blood gas parameters:
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) |
Acute respiratory alkalosis. Clinical scenario – Psychogenic hyperventilation
Let us dissect these results systematically.
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:
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.
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 |
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.
Let us dissect these results systematically.
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.
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.
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.
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.
Let us dissect these results systematically.
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.
Loverro, G., et al. "Indications and outcome for intensive care unit admission during puerperium." Archives of gynecology and obstetrics 265.4 (2001): 195-198.
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 |
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.
Let us dissect these results systematically.
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.
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.
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 |
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
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.
Thus, there is a triple disorder here:
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:
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.
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.
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.
Methanol (or some other alcohol) toxicity.
High anion gap acidosis, increased osmolar gap.
Let us dissect these results systematically.
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.
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.
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.
Distal (Type 1) RTA
Hyperchloraemic, normal AG acidosis and severe hypoK, with normal renal function and positive urinary anion gap.
Let us dissect these results systematically.
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.
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.
For each set of the following biochemical and arterial blood gas parameters:
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) |
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.
Let us dissect these results systematically.
Situations which might give rise to such findings include
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.
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
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.
a) Lithium toxicity.
b) Negative anion gap and history of depression.
Let us dissect these results systematically.
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:
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.
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 |
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.
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.
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?
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.
Let us dissect these results systematically.
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.
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.
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.
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).
Let us dissect these results systematically.
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):
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.
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.
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?
a) Hypoadrenalism or Addisonian crisis.
b) Random cortisol.
Let us dissect these results systematically.
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.
And yes, to confirm hypoadrenalism, one would ask for a random cortisol, as well as a short synacthen test. 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. As a reader had pointed out (thank you Damian), this may be an allusion to the increased risk of a cold-loving northdweller being exposed to the hot sweatiness of a Mediterranean holiday. As Dineen et al (2019) had put it, "In the case of a hot climate or strong perspiration, it is necessary to increase the fludrocortisone dose (0.1–0.2mg/ day) or the salt intake to compensate."
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.
Dineen, Rosemary, Christopher J. Thompson, and Mark Sherlock. "Adrenal crisis: prevention and management in adult patients." Therapeutic advances in endocrinology and metabolism 10 (2019): 2042018819848218.
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?
a) Normal anion gap severe metabolic acidosis with incomplete compensation.
b) Renal tubular acidosis Type 1 distal secondary to chronic toluene abuse.
Let us dissect these results systematically.
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.
Batlle, D. C., S. Sabatini, and N. A. Kurtzman. "On the mechanism of toluene-induced renal tubular acidosis." Nephron 49.3 (1988): 210-218.
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.
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
Let us dissect these results systematically.
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
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
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.
a)
b)
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.
Let us dissect these results systematically.
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
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
Ventilation
Circulation
Shock state needs to be investigated; potential causes include
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
Electrolytes
Fluid balance
Abdominal injuries
Haematological disturbances
Infectious complications
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.
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.
a)
Metabolic alkalosis (PCO2 appropriate using 0.7 x [HCO3] + 20 +/- 5) A-a DO2 = 295 (P/F 130 “moderate” ARDS)
b)
Let us dissect these results systematically.
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.
Khanna, Apurv, and Neil A. Kurtzman. "Metabolic alkalosis." J NEPHROL 2006; 19 (suppl 9): S86-S96
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.
Let us dissect these results systematically.
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).
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.
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.
a) Rhabdomyolysis.
b)
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:
Rhabdomyolysis is discussed at greater length in the discussion of Question 16 from the first paper of 2008.
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.
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.
a)
b)
Let us dissect these results systematically.
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.
Thus, investigations could include any two of the following:
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.
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?
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.
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:
Thus, acid-base disorders can be classified as:
Advantages of the Stewart method:
Disadvantages of the Steward method:
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.
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.
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.
This question is identical to Question 18.2 from the first paper of 2011.
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 |
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.)
Let us dissect these results systematically.
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
Endocrine and metabolic disturbances
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.
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.
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 |
Raised osmolar gap with normal AG
Mannitol
Glycine
Ethanol
Let us dissect these results systematically.
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:
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.
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.
a)
Mixed respiratory and metabolic alkalosis
b)
Respiratory alkalosis from the hyperventilation due to the pneumonia
Metabolic alkalosis from vomiting (or diuretic use).
Let us dissect these results systematically.
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.
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
a)
Let us dissect these results systematically.
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
Risk factors for dysfunction of 5-oxoprolinase
Risk factors for diminished 5-oxoproline clearance
The college also include old age as a risk factor.
d)
Specific management consists of addressing the synthesis and clearance of 5-oxoproline.
Thus:
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.
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.
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)
a)
Let us dissect these results systematically.
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:
Type A lactic acidosis: impaired tissue oxygenation
Type B1 lactic acidosis, due to a disease state
|
Type B2 drug-induced lactic acidosis
Type B3 : inborn errors of metabolism
|
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.
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)
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.)
Let us dissect these results systematically.
It is pleasing to see the use of Stewart's physicochemical approach to acid-base analysis in the college answer.
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)
Lactic acidosis
Anion gap elevation (37 mEq/L)
Metabolic alkalosis
Respiratory alkalosis
This is a triple disorder.
Let us dissect these results systematically.
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)
Acute respiratory acidosis with metabolic alkalosis
Clinical scenario – acute respiratory failure in COAD (Acute on chronic respiratory failure)
Let us dissect these results systematically.
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)
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.
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
Compartment shift
Metabolism by live cells
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.
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)
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
Let us dissect these results systematically.
Thus, there is:
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).
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)
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
Let us dissect these results systematically.
So, in summary, the blood abnormalities are:
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.
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.
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)
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.
a) Let us dissect the results systematically:
Thus, in summary:
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.
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.
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)
a)
Metabolic alkalosis
Raised A-a gradient
b)
Diuretics
Steroids
NG losses
Post hypercapnia
A systematic approach to this problem would resemble the following:
In summary:
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.
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.
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)
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:
Let us dissect these results systematically.
In summary:
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)
a)
b)
a)
Let us dissect these results systematically.
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.
Generic causes of a lactic acidosis are also offered below, for completeness
Type A lactic acidosis: impaired tissue oxygenation
Type B1 lactic acidosis, due to a disease state
|
Type B2 drug-induced lactic acidosis
Type B3 : inborn errors of metabolism
|
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)
a)
b)
a)
Let us dissect these results systematically.
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.
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.
Define the terms 'base excess' and 'standard base excess' (20% marks)
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.
In brief:
Base excess definition
Standard base excess
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.
Critically evaluate the role of monitoring blood lactate levels in the critically ill
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
Evidence:
Three studies have looked at lactate-directed versus non-lactate-directed therapy in:
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:
Overall:
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:
Rationale for lactate monitoring in critical illness
Advantages of lactate monitoring in critical illness
Errors of lactate measurement
Errors of lactate interpretation
Evidence for and against the use of lactate as a biomarker
Lactate as a prognostic marker:
Lactate as a guide to therapy:
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.
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)
a) Mixed respiratory, high anion gap and normal anion gap metabolic acidosis.
b) Toxidrome – sympathomimetic agent.
a)
Let us dissect these results systematically.
The college only wanted us to comment on the acid-base abnormalities, but other features are also interesting. In summary:
b)
Informed by the above features, the differentials must include:
If he didn't come from the street, malignant hyperthermia would also have to be mentioned.
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)
a)
Raised anion gap metabolic acidosis, lactic acidosis, with appropriate respiratory compensation (Anion gap 143 – 115 = 28)
b)
Let us dissect these results systematically.
Thus, this is a pure lactic acidosis.
b)
Causes of such extreme lactic acidosis?
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)
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
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.
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).
Fernández-Rodríguez, E., and E. Camarero-González. "[Patient with Crohn's disease and seizures due to hypomagnesemia]." Nutricion hospitalaria 22.6 (2006): 720-722.
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)
Let us dissect this systematically:
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)
Let us dissect this systematically;
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.
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.
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)
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
A systematic approach:
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.
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)
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
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:
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.
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)
a)
b)
Specific details of the assays not required.
To go though it systematically:
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.
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.
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)
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.
a)
Let's dissect this systematically. First, the acid-base disturbance
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:
The other abnormalities (and explanations) are:
b)
Biochemistry
Imaging
Adrogué, Horacio J., and Nicolaos E. Madias. "Hypernatremia." New England Journal of Medicine 342.20 (2000): 1493-1499.
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)
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
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 CO2 = (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:
Explanations? "Potential reasons for each"?
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.
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 |
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.
Another disembodied gas, not even a stumpy end of a clinical setting.
To approach this systematically:
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)
Rawla, Prashanth, et al. "Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma." Endocrinology, diabetes & metabolism case reports 2017.1 (2017).
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 |
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
Let us dissect these results systematically:
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:
Other unofficial possibilities include:
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 |
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.
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:
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".
List the causes of an elevated lactate immediately following an aortic valve replacement procedure.
Outline your approach to determining the cause.
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
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:
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.
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.
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 |
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
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:
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 :
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.
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 |
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.
"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.
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 |
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)
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.
Let us dissect these data;
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:
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.
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)
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.
Let us dissect these data;
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.
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.
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 |
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.
"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:
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:
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.
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 |
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
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:
Anions |
Cations |
Chloride depletion
Bicarbonate excess (real or apparent)
|
Potassium depletion
Calcium excess
|
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.
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 |
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)
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).
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.
A 60-year-old male with alcoholic cirrhosis and atrial fibrillation on regular flucloxacillin and paracetamol is admitted to your ICU post-variceal banding. His coagulation screen is displayed below:
Parameter |
Patient Value |
Adult Normal Range |
Prothrombin time (PT) |
28.0 sec* |
12.0 – 16.5 |
International normalised ratio (INR) |
2.4* |
0.9 – 1.3 |
Activated partial thromboplastin time (APTT) |
21.0 sec |
27.0 – 38.5 |
Fibrinogen |
2.1 g/L |
2.0 – 4.0 |
D-Dimer |
0.5 mg/L |
< 0.5 |
The arterial blood gas and biochemistry results from the same patient are given below:
Parameter |
Patient Value |
Adult Normal Range |
FiO2 |
0.21 |
|
pH |
7.23* |
7.35 – 7.45 |
pO2 |
90 mmHg (12 kPa) |
|
pCO2 |
22.0 mmHg (2.93 kPa)* |
35.0 – 45.0 (4.60 – 6.00) |
SpO2 |
92% |
|
Bicarbonate |
9.0 mmol/L* |
22.0 – 26.0 |
Base Excess |
-16.7 mmol/L* |
-2.0 to +2.0 |
Lactate |
1.3 mmol/L |
0.5 – 1.6 |
Parameter |
Patient Value |
Adult Normal Range |
Sodium |
135 mmol/L |
135 – 145 |
Potassium |
4.0 mmol/L |
3.5 – 5.0 |
Chloride |
100 mmol/L |
95 – 105 |
Bicarbonate |
9.0 mmol/L* |
22.0 – 26.0 |
Glucose |
6.0 mmol/L |
3.5 – 6.0 |
Urea |
7.0 mmol/L |
3.0 – 8.0 |
Creatinine |
120 μmol/L* |
45 – 90 |
Examiners Comments:
When asked for a specific number of responses (e.g. 'three causes of') please supply this number of responses. Extra responses will not gain extra marks. If there are more causes, then list the most likely. Many candidates did not appear to pay attention to the mark allocation and gave insufficient detail in sections of the question worth the most marks.
1) An isolated normal PT in a middle-aged alcoholic with known AF? What could it be??
2) A systematic approach to this gas:
Thus, this is a well-compensated severe metabolic acidosis with a high anion gap. And it's not due to lactate or uraemia. To apply a well-worn mnemonic, the differentials are
The investigations, therefore, are:
EMMETT, MICHAEL, and ROBERT G. NARINS. "Clinical use of the anion gap."Medicine 56.1 (1977): 38-54.
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 clini
A 32-year-old male is admitted to your ICU after an appendicectomy for a perforated appendix. He has a background of schizoaffective disorder. On admission, he is receiving vasopressor support with noradrenaline at 7 mcg/min. and has a temperature of 41ºC. The first arterial blood gas on admission is given below:
Parameter | Patient Value | Adult Normal Range |
FiO2 | 50% | |
pH |
7.01* |
7.35 – 7.45 |
pO2 |
120.0 mmHg (16.4 kPa) |
|
pCO2 |
58.0 mmHg (9.6 kPa)* |
35.0 – 45.0 (4.6 – 6.0) |
SpO2 |
96% |
|
Bicarbonate |
14.0 mmol/L* |
22.0 – 26.0 |
Base Excess |
-15.0 mmol/L* |
-2.0 to +2.0 |
Lactate |
8.5 mmol/L* |
0.5 – 1.6 |
Sodium |
135 mmol/L |
135 – 145 |
Potassium |
5.2 mmol/L* |
3.5 – 5.0 |
Chloride |
99 mmol/L |
95 – 105 |
Glucose |
8.0 mmol/L* |
3.5 – 6.0 |
a) Comment on the acid base status. (10% marks)
b) List four likely explanations for these findings other than sepsis. (10% marks)
So: let's go through this ABG systematically.
In summary, this is a severe high anion gap metabolic acidosis as well as a respiratory acidosis.
Four likely explanations for this? The college examiners have loaded this SAQ with plenty of background information. Specifically, they've given this patient a history of mental illness. The expectation here, of course, is that the candidates would form the impression of somebody who is likely to be using illicit drugs while recovering from appendicectomy. Because that's clearly what mentally ill people always do.
Anyway, the hints are:
Inevitably, the following elements must be in your list of differentials:
These are the four most likely culprits. The college throws thyrotoxicosis and transfusion reaction in there, but the history and biochemistry do nothing to promote those differentials. So if we're going to just throw random causes of lactic acidosis around, then, dear reader, have at you:
Type A lactic acidosis: impaired tissue oxygenation
Type B1 lactic acidosis, due to a disease state
|
Type B2 drug-induced lactic acidosis
Type B3 : inborn errors of metabolism
|
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.
A 58-year-old female presents with muscle weakness and fatigue. Her arterial blood gas is given below:
Parameter |
Patient Value |
Adult Normal Range |
FiO2 |
0.21 |
|
pH |
7.01* |
7.35 – 7.45 |
pO2 |
88.0 mmHg (5.6 kPa) |
|
pCO2 |
29.0 mmHg (3.9 kPa)* |
35.0 – 45.0 (4.6 – 6.0) |
Bicarbonate |
7.0 mmol/L* |
22.0 – 26.0 |
Base Excess |
-21.0 mmol/L* |
-2.0 to +2.0 |
Lactate |
0.5 mmol/L |
0.5 – 1.6 |
Sodium |
120 mmol/L* |
135 – 145 |
Potassium |
2.3 mmol/L* |
3.5 – 5.0 |
Chloride |
97 mmol/L |
95 – 105 |
Glucose |
4.8 mmol/L |
3.5 – 6.0 |
Urinary pH |
6.1 |
a) Comment on the acid base status. What is the likely cause for her symptoms and give a rationale for your answer. (30% marks)
A systematic dissection:
Thus, this is a severe normal anion gap metabolic acidosis, as well as a respiratory acidosis because of inadequate respiratory compensation. The urinary pH, however, is 6.1, which is completely useless. What are you doing, kidneys? You're supposed to be acidifying the urine... Clearly, there is a renal tubular acidosis happening here. Judging by the potassium, you'd expect the problem to be in the distal tubule (i.e. a Type 1 RTA).
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.
Ring, Troels, Sebastian Frische, and Søren Nielsen. "Clinical review: Renal tubular acidosis–a physicochemical approach." Critical Care 9.6 (2005): 573.
McCurdy, Donna Kern, Myron Frederic, and J. Russell Elkinton. "Renal tubular acidosis due to amphotericin B." New England Journal of Medicine 278.3 (1968): 124-131.
Cohen, Eric P., et al. "Absence of H (+)-ATPase in cortical collecting tubules of a patient with Sjogren's syndrome and distal renal tubular acidosis." Journal of the American Society of Nephrology 3.2 (1992): 264-271.
Pitts, Robert F. "Renal production and excretion of ammonia." The American journal of medicine 36.5 (1964): 720-742.
A 65-year-old male is found wandering and incoherent in the street before presenting to hospital. His arterial blood gas is shown below:
Parameter |
Patient Value |
Adult Normal Range |
FiO2 |
0.3 |
|
pH |
7.50* |
7.35 – 7.45 |
pO2 |
105 mmHg (14 kPa) |
|
pCO2 |
20.0 mmHg (1.9 kPa)* |
35.0 – 45.0 (4.6 – 6.0) |
SpO2 |
98% |
|
Bicarbonate |
15.0 mmol/L* |
22.0 – 26.0 |
Base Excess |
-7.3 mmol/L* |
-2.0 to +2.0 |
Lactate |
2.3 mmol/L* |
0.5 – 1.6 |
Sodium |
120 mmol/L* |
135 – 145 |
Potassium |
3.9 mmol/L |
3.5 – 5.0 |
Chloride |
71 mmol/L* |
95 – 105 |
Glucose |
11.0 mmol/L* |
3.5 – 6.0 |
a) Comment on the acid base status. (30% marks)
Respiratory alkalosis, concomitant high anion gap metabolic acidosis (AG 34, delta-delta ratio 2.44) and pre-existing metabolic alkalosis. (3 marks)
Systematically:
But why? Why is this 65 yo male wandering and incoherent? How did they come to have this fascinating mixed disorder? And what are all these extra anions? Is it a toxic alcohol? Did this person imbibe a vast quantity of essential oils? Is a salicylate overdose responsible for the respiratory alkalosis? Exploring these issues would have made a much more interesting question, one which might even test some sort of higher-order abilities. For the record, the ABG interpretation in the "systematically" section above was generated automatically using a script written in Google Sheets.
A 51-year-old male with a history of cirrhosis secondary to Hepatitis C is admitted for the first time with haematemesis. His gastroscopy is complicated by aspiration. He is admitted to ICU ventilated.
The following results were obtained:
Parameter |
Patient Value |
Adult Normal Range |
FiO2 |
0.4 |
|
pH |
7.16* |
7.35 – 7.45 |
pO2 |
109 mmHg (14.1 kPa) |
|
pCO2 |
29.0 mmHg (3.87 kPa)* |
35.0 – 45.0 (4.60 – 6.00) |
SpO2 |
95% |
|
Bicarbonate |
10.0 mmol/L* |
22.0 – 26.0 |
Base Excess |
-17.0 mmol/L* |
-2.0 – +2.0 |
Lactate |
4.5 mmol/L* |
0.5 – 1.6 |
Sodium |
144 mmol/L |
135 – 145 |
Potassium |
4.4 mmol/L |
3.5 – 5.0 |
Chloride |
114 mmol/L* |
95 – 105 |
Glucose |
11.0 mmol/L* |
3.5 – 6.0 |
Parameter |
Patient Value |
Adult Normal Range |
Urea |
17.0 mmol/L* |
3.0 – 8.0 |
Creatinine |
110 µmol/L* |
45 – 90 |
Albumin |
23 g/L* |
35 – 50 |
Protein |
41 g/L* |
60 – 80 |
Total bilirubin |
56 µmol/L* |
< 26 |
Aspartate transferase |
67 U/L* |
< 35 |
Alanine transferase |
101 U/L* |
< 35 |
Alkaline phosphatase |
78 U/L* |
30 – 110 |
g-Glutamyl transferase |
36 U/L |
< 40 |
Calcium (total) |
2.13 mmol/L |
2.12 – 2.62 |
Interpret these results, giving likely reasons for the abnormalities. (40% marks)
UEs: low HCO3 indicates metabolic acidosis, elevated Urea to Cr ratio likely related to GIT bleed (other causes are dehydration, excessive diuretics, high protein diet, steroids), elevated Cr likely due to kidney injury (likely pre-renal, renal causes possible (including hepatorenal syndrome), post-renal causes less likely).
ABG: There is an increased anion gap metabolic acidosis (20).
The delta ratio is 0.57 indicating a mixed high and a normal anion gap metabolic acidosis. High anion gap component likely secondary to shock from hypovolaemia, possibly sepsis from aspiration. Normal anion gap component may reflect saline resuscitation, renal impairment. There is partial respiratory compensation (expect the CO2 to be 23=1.5xHCO3 + 8), which is likely due to mechanical ventilation. There is an increased Aa gradient, presumably because of the aspiration. The elevated lactate may represent shock, liver impairment or treatment with catecholamines. Mildly elevated glucose presumably a stress response.
LFTS: Low albumin could indicate chronic synthetic liver disease or be due to acute sepsis/SIRS or related to volume expansion with non-albumin fluids. Elevated ALT related to hepatocellular injury most likely Hep C plus/minus hypoperfusion related to the haematemesis. Elevated bilirubin likely related to chronic cirrhosis (pre-hepatic causes are possible (including transfusion), and biliary obstruction is less likely as GGT/ALP not elevated).
This college answer is by far the best biochemistry answer CICM examiners have ever written, and should represent some kind of standard for all future examiners' answers. They will all be measured against it.
Let's start with the gas:
Thus, this is an ABG of a patient who is
As for the biochemistry:
You are called to the Emergency Department to see a 56-year-old female with a diagnosis of acute severe asthma .
She has been given 4 sequential salbutamol nebulisers (5 mg dose), 200 mg IV hydrocortisone, and 500 mcg of subcutaneous adrenaline with no improvement.
When you arrive in the Emergency Department, she has some inspiratory stridor, and is only able to talk in single words. She is flushed, in sinus rhythm at 125 beats/minute, and has a blood pressure of 160/90 mmHg (no paradox). She is breathing room air with an O2 saturation of 100%.
Auscultation reveals symmetrical breath sounds. There are no signs of heart failure.
An arterial blood gas analysis shows the following results:
Parameter |
Patient Value |
Adult Normal Range |
F i O2 |
0.21 | |
pH |
7.56* |
7.35 - 7.45 |
pO2 |
117 mmHg |
|
pCO2 |
16.0 mmHg |
35.0 - 45.0 (4.6 - 6.0) |
SpO2 |
100% |
|
Bicarbonate |
14.0 mmol/L* |
22.0 - 26.0 |
Base Excess |
-8.7 mmol/L* |
-2.0- +2.0 |
Lactate |
5.2 mmol/L* |
0.5 - 1.6 |
Sodium |
141 mmol/L |
135 - 145 |
Potassium |
3.5 mmol/L |
3.5 - 5.0 |
Chloride |
112 mmol/L* |
95 - 105 |
Glucose |
11.0 mmol/L* |
3.5 - 6.0 |
Ionised calcium |
1.21 mmol/L |
1.10-1.35 |
a) Interpret the arterial blood gas provided above. (20% marks)
b) What are the disturbances in physiology contributing to her breathlessness? (30% marks)
Let's do this ABG first:
So, this "asthmatic". The asthma history does not sound plausible, as asthma usually is not associated with stridor. Also, one might expect some wheeze on auscultation. Could this be something else?
Possible causes of respiratory alkalosis include:
Possible differentials include:
Grahame-Smith, D. G. "Progress report: the carcinoid syndrome." Gut 11.2 (1970): 189.
A 73-year-old female presents to the Emergency Department with breathlessness, after a minor car accident two days earlier. Since the accident, she has had pain in her left knee and chest pain on breathing and coughing. She has previously had bilateral knee replacements. She deteriorates over 3 hours in the Emergency Department and now looks unwell. Her vital signs are as follows:
An arterial blood gas analysis is performed along with other blood tests as shown below:
Parameter |
Patient Value |
Adult Normal Range |
FiO2 |
0.5 |
|
pH |
7.18* |
7.35 – 7.45 |
pO2 |
68 mmHg (9.1 kPa) |
|
pCO2 |
42.0 mmHg (5.6 kPa) |
35.0 – 45.0 (4.6 – 6.0) |
SpO2 |
91% |
|
Bicarbonate |
15.0 mmol/L* |
22.0 – 26.0 |
Base Excess |
-9.2 mmol/L* |
-2.0 – +2.0 |
Lactate |
3.4 mmol/L* |
0.5 – 1.6 |
Sodium |
135 mmol/L |
135 – 145 |
Potassium |
5.0 mmol/L |
3.5 – 5.0 |
Chloride |
105 mmol/L |
95 – 105 |
Glucose |
10.1 mmol/L* |
3.5 – 6.0 |
Urea |
12.0 mmol/L* |
3.0 – 8.0 |
Creatinine |
150 µmol/L* |
45 – 90 |
Albumin |
30 g/L* |
35 – 50 |
Total bilirubin |
36 µmol/L* |
< 26 |
Aspartate transferase |
405 U/L* |
< 35 |
Alanine transferase |
336 U/L* |
< 35 |
Alkaline phosphatase |
168 U/L* |
30 – 110 |
g-Glutamyl transferase |
198 U/L* |
< 40 |
Ionised calcium |
1.04 mmol/L* |
1.10 – 1.35 |
CRP |
186 mg/L* |
< 5 |
Haemoglobin |
114 g/L* |
120 – 160 |
White Cell Count |
1.7 x 109/L* |
4.0 – 11.0 |
Platelet count |
87 x 109/L* |
150 – 350 |
International normalised ratio (INR) |
1.4* |
0.9 – 1.3 |
Activated partial thromboplastin ratio (APTT ) |
41.0 sec* |
27.0 – 38.5 |
Fibrinogen |
4.0 g/L |
2.0 – 4.0 |
a) Interpret the arterial blood gas analysis provided on page 7. (20% marks)
b) List six differential diagnoses for her presentation. (30% marks)
Lack of respiratory compensation for acidosis (or alternatively, a co-existing respiratory acidosis).
A-a gradient of about 240, P:F ratio 136; implies severe hypoxia.
"Interpret the arterial blood gas analysis" is what they specifically asked for. Thus:
So: what are six differentials for this? The other bloods show a bunch of other abnormalities which we were not asked to report on:
So; integrating this with the salient features of history, you'd have to list the following differentials:
The following results were obtained from a 32-year-old female admitted with severe asthma.
Parameter | Patient Value |
Adult Normal Range |
FiO2 | 0.4 | |
pH | 6.92* | 7.35 – 7.45 |
PO2 | 81 mmHg (10.8 kPa) | |
PCO2 | 71.0 mmHg (9.5 kPa) * |
35.0 – 45.0 (4.6 – 6.0) |
SpO2 | 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. (40% marks)
Not available.
Let's go through this ABG in some detail.
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.
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 |
a) Comment on the abnormalities on this arterial blood gas. (15% marks)
b) List five likely causes for the acid-base disturbance. (15% marks)
Not available.
When invited to "comment on the abnormalities", one is always tempted to write "damn, those are some hideous abnormalities". As "comment" does not appear in the GLOSSARY OF TERMS at the beginning of the question paper, one must interpret this direction themselves. What they probably meant was "describe". "Describe the abnormalities on this arterial blood gas".
Let's go through this ABG in some detail.
So, for a measly 15% of the marks, in 1.5 minutes of writing, what could you possibly comment here?
a) The abnormalities on this gas are:
b) Five causes for this picture are easy to find. Most likely any reasonable answer would have been accepted. From AF being given as background history, one would absolutely have to include ischaemic gut due to embolic phenomena in their differentials (in fact it would have to be the first differential). Thus:
Ketoacidosis with dehydration could also go in there, but the glucose just looks too normal.
The following arterial blood gas was obtained from a 19-year-old chemistry student who presents with dyspnoea, cyanosis and feeling unwell. He has been handling chemicals today and admits to recreational drug use but takes no prescribed medicines. His observations on 8 L/min oxygen via a Hudson mask are as follows:
Temperature: 37.2ºC
Heart rate: 130 beats/min sinus
Blood Pressure: 140/73 mmHg
Oxygen Saturation: 82%
His initial arterial blood gas analysis is given below:
Parameter | Patient Value | Adult Normal Range |
FiO2 | 0.4 | |
pH | 7.45 | 7.35 – 7.45 |
pO2 | 219 mmHg (29.2 kPa) | |
pCO2 | 37.8 mmHg (5.04 kPa) | 35.0 – 45.0 (4.60 – 6.00) |
SpO2 | 98.1% | |
Bicarbonate | 26.6 mmol/L* | 22.0 – 26.0 |
Base Excess | 2.6 mmol/L* | -2.0 – +2.0 |
Lactate | 0.9 mmol/L | 0.5 – 1.6 |
Sodium | 139 mmol/L | 135 – 145 |
Potassium | 3.9 mmol/L | 3.5 – 5.0 |
Chloride | 107 mmol/L* | 95 – 105 |
Ionised Calcium | 1.18 mmol/L | 1.15 – 1.29 |
Glucose | 7.1 mmol/L* | 3.5 – 6.0 |
a) What is the diagnosis? (10% marks)
b) Name two recreational drugs and two chemical compounds that can cause this condition other than prescribed medicines. (20% marks)
c) What emergency treatment would you give? (20% marks)
d) In what circumstance would your treatment of choice be contraindicated? (10% marks)
Not available.
a) This is methaemoglobinaemia. The chemistry student is hopped up on nitrites. The specific clues to this diagnosis are
Thus, this is methaemoglobinaemia.
Now, one should point out that when you write "SpO2", the little "p" usually means "pulse", and so it is confusing and weird to see it in the ABG results. Usually the blood gas analyser will report an "SaO2", where the "a" stands for "arterial". It may seem pedantic to pick on these minor elements, but then some might say that ICU is all about being thorough and detailed. It is especially confusing to find this mistake in a question where specifically the difference between the pulse oximeter and the arterial oximeter is a critically important part of the diagnosis.
Anyway: methaemoglobinaemia.
b) Recreational drugs which cause methaemoglobinaemia are:
Non-recreational chemical compounds are numbered in the countless thousands; though the author confesses he has not personally audited this list to make sure none of these substances has any enjoyable effects. Briefly:
You could also have used use nitric oxide, so long as you mention that it is a part of internal combustion engine exhaust (even though it could theoretically also be used medically to treat pulmonary hypertension). In case it is necessary in some future version of this question, prescribed medicines which cause methaemoglobinaemia include:
c) Emergency treatment of methaemoglobinaemia:
This is discussed in much more detail in Question 1 from the second paper of 2004, where it was a full 10-mark question. Here, for 20% of the mark, you would only have time to write this much:
d) "your treatment of choice be contraindicated" if the patient has G6PD deficiency. If your treatment of choice was ascobic acid, you would be just fine.
Wright, Robert O., William J. Lewander, and Alan D. Woolf. "Methemoglobinemia: etiology, pharmacology, and clinical management."Annals of emergency medicine 34.5 (1999): 646-656.
ROSEN, PETER J., et al. "Failure of methylene blue treatment in toxic methemoglobinemiaAssociation with glucose-6-phosphate dehydrogenase deficiency." Annals of internal medicine 75.1 (1971): 83-86.
A 44-year-old male presents following an intentional overdose. His arterial blood gases (ABG) are presented below:
Parameter |
Patient Value |
Adult Normal Range |
FiO2 |
0.21 |
|
pH |
7.36 |
7.35 – 7.45 |
pCO2 |
16.0 mmHg (2.13 kPa) * |
35.0 – 45.0 (4.60 – 6.00) |
pO2 |
111 mmHg (14.8 kPa) |
|
SpO2 |
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)
His lactate as measured on ABG is 25 mm/L, but the result on a venous 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)
Not available.
How very exciting. This SAQ must have been sitting on somebody's desk for two decades now, waiting for its turn. Yes, reader, this is a case of the fabled lactate gap, described in loving detail by Bala Venkatesh in his 2002 grimoire, Data Interpretation in Critical Care Medicine. It goes without saying that all trainees should own this book, as it has been a source of countless weird metabolic problems and ABG interpretation questions. Interestingly (in case anybody is interested), the patient data in this SAQ are totally different to the ABG in Venkatesh's book (Question 1.12), but exactly the same as Question 20.2 from the second paper of 2017.
But first, a), the acid base abnormalities:
but, the lactate
Yes; the discrepancy between the lab lactate and the gas lactate is due to the lactate electrode being confused by the glycolic acid in this patient's bloodstream. The patient has obviously overdosed on ethylene glycol.
The amperometric measurement of lactate uses the lactate-sensitive electrode, 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.
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.
The following results were obtained from a 32-year-old male:
Parameter |
Patient Value |
Adult Normal 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 (4.0 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.
a) What is the underlying mechanism for the primary abnormality?
(20% marks)
Not available.
This question is identical to Question 3.4 from the second paper of 2013.
Let us dissect these results systematically.
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.
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.
A 54-year-old male presents with new onset confusion followed by seizures and convulsions, leading to intubation. His full blood count is shown:
Parameter |
Patient Value |
Adult Normal Range |
Haemoglobin |
105 g/L* |
135 – 145 |
Mean Cell Volume |
98 fL |
80 – 100 |
Platelets |
67 x 109/L* |
150 – 400 |
White Cell Count |
110 x 109/L* |
4 – 11 |
Blasts |
52%* |
0 |
a) What is the likely cause of his presentation and underlying diagnosis?
b) What other organ is most likely to be affected by this phenomenon?
(15% marks)
Post intubation, the patient’s SpO2 holds steady at 98% on FiO2 25%. An arterial blood gas result arrives from the lab:
Parameter |
Patient Value |
Adult Normal Range |
pH |
7.31* |
7.35 – 7.45 |
PaCO2 |
54 mmHg* |
35 – 45 |
PaO2 |
45 mmHg* |
80 – 100 |
SpO2 |
67%* |
93 – 100 |
c) What is the likely cause of this discrepancy? (10% marks)
Not available.
a) This is some sort of horrible blast crisis due to an acute haematological malignancy. From the presented data it would be impossible to say what kind of malignancy with any precision, apart from narrowing it down to some sort of leukaemia.
b) "What other organ is most likely to be affected by this phenomenon" is a strange question to ask in this top-tier elite exit exam, as it is not clear what it's testing apart from basic reading comprehension. The stem clearly gave us seizures and coma. This blast crisis patient probably has some kind of leukostasis-related complication related to an increase in their blood viscosity (most likely either an ischaemic stroke or a cerebral venous sinus thrombosis). If the reader interpreted the question as asking "other than the brain, what other organ is most likely to be affected by this process?" then the answer could include:
c) This is "leukocyte larceny", spurious hypoxemia on the ABG which is the consequence of ongoing metabolism of the oxygen by the blasts in the sample. One must nod approvingly at the college examiners who introduced a sample processing delay into the question ("arrives from the lab" they mentioned quietly, i.e. it was not analysed by a locally available point-of-care device which would usually eliminate this phenomenon). While the intern was running the blood gas to pathology, the blasts in the syringe were misappropriating all the oxygen like Russian oligarchs. The result was a falsely depressed PaO2 in the sample. The lab would not have to be very far away: according to the data collected by Fox et al, the rate of metabolism can be very rapid. For blood samples with the highest WCC counts, the investigators observed a PaO2 drop of up to 72 mmHg over two minutes.
Sacchetti, Alfred, et al. "Leukocyte larceny: spurious hypoxemia confirmed with pulse oximetry." The Journal of emergency medicine 8.5 (1990): 567-569.
Fox, Michael J., et al. "Leukocyte larceny: a cause of spurious hypoxemia." The American journal of medicine 67.5 (1979): 742-746.
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 |
Adult Normal Range |
FiO2 |
0.6 |
|
pH |
6.91* |
7.35 – 7.45 |
pCO2 |
64 mmHg (8.5 kPa)* |
35 – 45 (4.6 – 6.0) |
pO2 |
158 mmHg (21 kPa)* |
75 – 98 (10 – 13) |
SaO2 |
96% |
|
Bicarbonate |
12 mmol/L* |
22 – 26 |
Base Excess |
-18 mmol/L* |
-2 – +2 |
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* |
< 2 |
(30% marks)
Not available.
This question is identical to Question 4.1 from the first paper of 2016, except instead of "Give six possible causes for this clinical and biochemical scenario", the question itself was revised into something a lot more reasonable, with clearer expactations.
Let us dissect these results systematically.
Thus, this is an almost completely pure HAGMA and a respiratory acidosis.
Why the lactate? Only three reasons?
In the last iteration of this SAQ, where six reasons for the clinical scenario were asked for, the college had also included local anaesthetic toxicity, dystonic drug reaction, intra-abdominal catastrophe, myocardial infarction, anaphylaxis and subarachnoid haemorrhage.
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.
Parameter |
Patient Value |
Adult Normal Range |
pH |
7.06* |
7.32 – 7.43 |
PCO2 |
42 mmHg (5.5 kPa) |
27 – 50 (3.5 – 6.6) |
PO2 |
44 mmHg (5.8 kPa) |
36 – 44 (4.7 – 5.8) |
Bicarbonate |
11 mmol/L* |
22 – 38 |
Base Excess |
-18 mmol/L* |
-3 – +3 |
O2 Saturation |
80% |
70 – 80 |
Sodium |
140 mmol/L |
135 – 145 |
Potassium |
3.8 mmol/L |
3.5 – 5.2 |
Chloride |
119 mmol/L* |
95 – 110 |
Calcium Ionised |
1.30 mmol/L |
1.12 – 1.32 |
Glucose |
10.6 mmol/L* |
3.0 – 5.4 |
Lactate |
1.0 mmol/L |
< 1.5 |
Haemoglobin |
116 g/L |
115 – 160 |
Urea |
9.3 mmol/L* |
3.0 – 8.0 |
Creatinine |
244 mmol/L* |
45 – 90 |
a) State the acid-base disturbance in the above results.
b) List three likely explanations for the acid-base status.
(30% marks)
Not available.
This question, with the exception of trivial changes in the question wording, is identical to Question 4.2 from the first paper of 2016.
a) State the acid-base disturbance in the above results.
Let us dissect these results systematically.
Thus, this is a pure NAGMA and a respiratory acidosis. The interesting question of whether you can call respiratory acidosis on the basis of a venous CO2 is debated in the discussion section from Question 4.2 (tl;dr: yes, it's usually reasonable, but not when the patient is as shocked as this, where the A-v CO2 difference could be quite large).
b) List three likely explanations for the acid-base status.
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.
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.
Hypoalbuminemia is common in the long-term ICU patient.
a) How does this finding alter your interpretation of acid-base data?
b) List two methods of how you would adjust for this.
(40% marks)
Not available.
This is an excellent stem made surprising only by the fact that we have never seen the like of it in CICM past papers. Certainly, through history, CICM trainees have been asked to adjust their calculations for albumin, but never have they been asked to spell out the exact scenarios where this is necessary, or how they would do it.
Moreover, the question specifically asked for the ways in which hypoalbuminaemia bedevils acid-base interpretation (i.e. mentioning calcium correction would probably not have scored any marks). The longer version of these explanations is available in the short chapter on the sources of error in blood gas analysis. Here, only a brief point-form answer is attempted, commensurate with the modest 40% weighting of the question.
a) How does hypoalbuminaemia alter your interpretation of acid-base data?
b) List two methods of how you would adjust for this.
For the reader who wants to add more to this answer and who enjoys complex equations, the best single resource which seems to collect them all is Patrick J. Nelligan's chapter on the diagnosis of acid-base disorders from Evidence-Based Practice of Critical Care (2010).
Neligan, Patrick J., and Rory O’Donoghue. "56 How Should Acid-Base Disorders Be Diagnosed and Managed?." Clifford S. Deutschman A2MS A2MD A2FCCM, Patrick J. Neligan, MA, MB, FRCARCSI, eds. Evidence-Based Practice of Critical Care. Philadelphia: WB Saunders (2010): 389-396.
Story, David A., Hiroshi Morimatsu, and Rinaldo Bellomo. "Strong ions, weak acids and base excess: a simplified Fencl–Stewart approach to clinical acid–base disorders." British journal of anaesthesia 92.1 (2004): 54-60.
Rossing, T. H., N. Maffeo, and V. Fencl. "Acid-base effects of altering plasma protein concentration in human blood in vitro." Journal of applied physiology 61.6 (1986): 2260-2265.
Berend, Kenrick. "Diagnostic use of base excess in acid–base disorders." New England Journal of Medicine 378.15 (2018): 1419-1428.
A 24-year-old female with a history of depression presents with seizures and decreased consciousness. Her arterial blood gas analysis is shown below, taken on FiO2 0.3.
Parameter |
Patient Value |
Adult Normal Range |
Barometric pressure |
760 mmHg (100 kPa) |
|
pH |
7.39 |
7.35 – 7.45 |
PCO2 |
40 mmHg (5.3 kPa) |
35 – 45 (4.6 – 6.0) |
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 |
4.0 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) State the reasoning for your answer.
(20% marks)
Not available.
This question is identical to Question 3.1 from the second paper of 2013. The only difference is that you are asked to "state the reasoning for your answer", whereas in 2013 you merely had to "give your reasoning". One's imagination swims with terrible ideas as to the causes and meanings of these changes.
Let us dissect these results systematically.
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:
Marshall, John C. "Gastrointestinal flora and its alterations in critical illness."Current Opinion in Critical Care 5.2 (1999): 119.
van Saene, H. K. F., et al. "Microbial gut overgrowth guarantees increased spontaneous mutation leading to polyclonality and antibiotic resistance in the critically ill." Current drug targets 9.5 (2008): 419-421.
Camus, Christophe, et al. "Short-Term Decline in All-Cause Acquired Infections With the Routine Use of a Decontamination Regimen Combining Topical Polymyxin, Tobramycin, and Amphotericin B With Mupirocin and Chlorhexidine in the ICU: A Single-Center Experience*." Critical care medicine 42.5 (2014): 1121-1130.
Daneman, Nick, et al. "Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis." The Lancet infectious diseases 13.4 (2013): 328-341.
Price, Richard, Graeme MacLennan, and John Glen. "Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis." BMJ: British Medical Journal 348 (2014).
Petros, Andy J., et al. "2B or Not 2B for Selective Decontamination of the Digestive Tract in the Surviving Sepsis Campaign Guidelines." Critical care medicine 41.11 (2013): e385-e386.
Hurley, James C. "Paradoxical ventilator associated pneumonia incidences among selective digestive decontamination studies versus other studies of mechanically ventilated patients: benchmarking the evidence base." Crit Care15 (2011): R7.
Ochoa-Ardila, María E., et al. "Long-term use of selective decontamination of the digestive tract does not increase antibiotic resistance: a 5-year prospective cohort study." Intensive care medicine 37.9 (2011): 1458-1465.
Hurley, James C. "The perfidious effect of topical placebo: A calibration of Staphylococcus aureus Ventilator Associated Pneumonia incidence within Selective Digestive Decontamination (SDD) studies versus the broader evidence base." Antimicrobial agents and chemotherapy (2013): AAC-00424.
Liberati, Alessandro, et al. "Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care." Cochrane Database Syst Rev 1 (2004).
Safdar, Nasia, Adnan Said, and Michael R. Lucey. "The role of selective digestive decontamination for reducing infection in patients undergoing liver transplantation: A systematic review and meta‐analysis." Liver transplantation10.7 (2004): 817-827.
Derde, L. P. G., and M. J. M. Bonten. "Controlling antibiotic resistance in intensive care units." Netherlands Journal of Critical Care, VOLUME 19 - NO 1 - FEBRUARY 2015
De Smet, A. M. G. A., et al. "Decontamination of the digestive tract and oropharynx in ICU patients." New England Journal of Medicine 360.1 (2009): 20.
Cuthbertson, B. H., et al. "A study of the perceived risks, benefits and barriers to the use of SDD in adult critical care units (The SuDDICU study)." Trials 11.1 (2010): 117.
A 50-year-old female is admitted to ICU following an elective anterior communicating artery aneurysm clipping procedure. The patient was extubated post-procedure. Her background medical conditions include hypertension, Type 2 diabetes mellitus (T2DM) and dyslipidaemia. Her medications include perindopril, metformin, pioglitazone, empagliflozin, and atorvastatin. The following arterial blood gas analysis was taken on day 2 post-operative.
Parameter | Patient Value | Adult Normal Range | ||||||||||
FiO2 | 0.21 | |||||||||||
pH | 6.81* | 7.35 – 7.45 | ||||||||||
pO2 | 138 mmHg (18.4 kPa) | |||||||||||
pCO2 | 11.0 mmHg (1.5 kPa)* | 35.0 – 45.0 (4.6 – 6.0) | ||||||||||
SpO2 | 98% | |||||||||||
Bicarbonate | 2.0 mmol/L* | 22.0 – 26.0 | ||||||||||
Base Excess | -31.3 mmol/L* | -2.0 – +2.0 | ||||||||||
Lactate | 3.2 mmol/L* | 0.5 – 1.6 | ||||||||||
Sodium | 142 mmol/L | 135 – 145 | ||||||||||
Potassium | 4.3 mmol/L | 3.5 – 5.0 | ||||||||||
Chloride | 116 mmol/L* | 95 – 105 | ||||||||||
Glucose | 10.5 mmol/L* | 3.5 – 6.0 | ||||||||||
Osmolal gap | 8 | < 10 |
a) List the abnormalities on the blood gas analysis. (20% marks)
b) Explain the most likely diagnosis and outline how you would investigate this further.
(20% marks)
Not available.
Empagliflozin? They are basically throwing this at you.
No, wait, wait. Let us dissect these results systematically.
So, this high anion gap metabolic acidosis in a euglycaemic diabetic. What could this possibly be?
Euglycaemic ketoacidosis comes to mind. It is the natural conclusion in this situation, where the stem clearly gives a history of an SGLT2 inhibitor. It is possible that the college would have wanted more detail, as they asked to "explain" rather than "list" or "give" the most likely diagnosis. In that case, one could go into the mechanism, where:
Or at least that's the shortest version of a mechanism described by Bui & Nawathe (2018). Now, to "outline how you would investigate this further". The diagnosis of EDKA rests on the finding of a high anion gap acidosis with raised ketones, where the BSL is below 200 mg/dL, which is 11.1 mmol/L in local terms (Barski et al, 2019). So... a blood ketone level is "how you would investigate this further". However, the college have attributed 20% of the marks to this question, which suggests they might have expected something more than just a one-liner. If one felt compelled to write more, one could hold forth as follows:
Kalra, Sanjay, and Yashdeep Gupta. "The insulin: glucagon ratio and the choice of glucose-lowering drugs." Diabetes Therapy 7.1 (2016): 1-9.
Wahid, Maryam, Abdul Khaliq Naveed, and Imad Hussain. "Insulin and glucagon ratio in the patho-physiology of diabetic ketoacidosis and hyperosmolar hyperglycemic non-ketotic diabetes." Journal of the College of Physicians and Surgeons--pakistan: JCPSP 16.1 (2006): 11-14.
Bui, Patrick, and Amar C. Nawathe. "Euglycemic Diabetic Ketoacidosis: Challenge is in the Diagnosis." Proceedings of UCLA Healthcare 22 (2018).
Barski, Leonid, et al. "Euglycemic diabetic ketoacidosis." European journal of internal medicine 63 (2019): 9-14.
A 64-year-old female patient is admitted to ICU following lung volume reduction surgery for bullous emphysematous lung disease. She is an ex-smoker with 40 pack year history, with a background history of hypertension and cor pulmonale. She was extubated post-procedure, prior to ICU admission. Her medications include amlodipine, frusemide, and bronchodilators. The following blood gas analysis was done on day 2 post-operative.
Parameter | Patient Value | Adult Normal Range | ||||||||||||
FiO2 | 0.25 | |||||||||||||
pH | 7.40 | 7.35 – 7.45 | ||||||||||||
pO2 | 57 mmHg (7.6 kPa) | |||||||||||||
pCO2 | 64.0 mmHg (8.5 kPa)* | 35.0 – 45.0 (4.6 – 6.0) | ||||||||||||
SpO2 | 88% | |||||||||||||
Bicarbonate | 39.0 mmol/L* | 22.0 – 26.0 | ||||||||||||
Base Excess | 12.3 mmol/L* | -2.0 – +2.0 | ||||||||||||
Lactate | 0.8 mmol/L | 0.5 – 1.6 | ||||||||||||
Sodium | 134 mmol/L* | 135 – 145 | ||||||||||||
Potassium | 4.4 mmol/L | 3.5 – 5.0 | ||||||||||||
Chloride | 101 mmol/L | 95 – 105 | ||||||||||||
Glucose | 7.7 mmol/L* | 3.5 – 6.0 |
Not available.
Let us dissect these results systematically:
So. This is a double disorder, a metabolic alkalosis as well as a respiratory acidosis. This heavy smoker has just had some of her gas exchange surface removed, and is under the effects of opiates following surgery, which explains this underwhelming respiratory performance. The metabolic alkalosis could be explained by some degree of chronic renal adaptation to hypercapnia, as well as the effects of long-term frusemide therapy.
A 72-year-old female is admitted to ICU after decortication of her left lung, due to empyema. Her background history includes insulin dependent diabetes mellitus, rheumatoid arthritis and hypertension. She was previously hospitalised 2 weeks ago for a methicillin sensitive Staphylococcus aureus bacteremia, and is on high dose intravenous flucloxacillin. She is persistently febrile.
Parameter | Patient Value | Adult Normal Range | ||||||||||
FiO2 | 0.6 | |||||||||||
pH | 6.94* | 7.35 – 7.45 | ||||||||||
pO2 | 85.0 mmHg (11.3 kPa) | |||||||||||
pCO2 | 43.0 mmHg (5.7 kPa) | 35.0 – 45.0 (4.6 – 6.0) | ||||||||||
SpO2 | 98% | |||||||||||
Bicarbonate | 9.0 mmol/L* | 22.0 – 26.0 | ||||||||||
Base Excess | -15 mmol/L* | -2.0 – +2.0 | ||||||||||
Lactate | 4.0 mmol/L* | 0.5 – 1.6 | ||||||||||
Sodium | 141 mmol/L | 135 – 145 | ||||||||||
Potassium | 5.0 mmol/L | 3.5 – 5.0 | ||||||||||
Chloride | 92 mmol/L* | 95 – 105 | ||||||||||
Glucose | 3.8 mmol/L | 3.5 – 6.0 | ||||||||||
Urea | 18.0 mmol/L* | 3.0 – 8.0 | ||||||||||
Creatinine | 145 μmol/L* | 45 – 90 |
a) List the abnormalities on the blood gas analysis. (15% marks)
b) Outline how you would investigate this further. (15% marks)
Not available.
Let us dissect these results systematically:
So, on this gas, there is:
So: wherever the stem volunteers a history of flucloxacillin or MSSA, the expectation is that the trainees will mention pyroglutamic acidosis in their list of differentials. However, this is a diabetic and she has renal failure. So: relevant investigations should include:
A 50-year-old female with a history of depression and osteoarthritis has presented to hospital with a suspected ingestion of 50 tablets of Panadol Osteo® (modified release paracetamol 665 mg/tablet). It is believed there was suicidal intent and roughly occurred five hours prior. She remains asymptomatic, is remorseful of her actions, and quite anxious.
Her vital parameters are stable; and paracetamol level is plotted in the nomogram below (Figure 12.1):
a) Outline the initial specific investigations and management. (30% marks)
b) Explain the role and rationale of N-acetylcysteine (NAC) (based on nomogram) in this patient.
(30% marks)
c) List the criteria for cessation in patients who require NAC beyond 20 hours. (20% marks)
d) List the criteria for consultation with liver transplant unit in patients with paracetamol toxicity.
(20% marks)
Not available.
The original college nomogram is not available, so this one is entirely the invention of the author.
Anyway: this is a relatively large overdose, 33.25g. Assuming this lady weighs 70kg, that would be 475mg/kg, an overdose which would be described as "massive" by local definitions.
a) Initial specific investigations and management:
Role and rationale of N-acetylcysteine (NAC) (based on nomogram) in this patient
The criteria for cessation in patients who require NAC beyond 20 hours:
Criteria for referral to a liver transplant unit:
Chiew, Angela L., et al. "Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand." Medical journal of Australia 212.4 (2020): 175-183.
The actual guideline document itself is marvellously comprehensive and contains everything you could possibly want for this SAQ:
A 38-year-old female presents to the Emergency Department with complaints of lower abdominal pain and vaginal bleeding. On examination, she is confused and, with cool peripheral perfusion and patchy ecchymoses over her extremities. Vaginal examination reveals clots, with tissue resembling products of conception. She is tachypneic, tachycardic with a non-invasive blood pressure of 88/42 mmHg.
(Parts 24.1 and 24.2 of the question are related to the initial blood results obtained from this patient.)
A peripheral venous blood sample including a venous blood gas analysis shows the following results:
Parameter | Patient Value | Adult Normal Range | |||||||||||||
FiO2 | 0.21 | ||||||||||||||
pH | 7.36 | 7.35 – 7.45 | |||||||||||||
pO2 | 46.0 mmHg (6.0 kPa) | ||||||||||||||
pCO2 | 20.0 mmHg (2.6 kPa)* | 45.0 – 51.0 (5.5 – 6.8 KPa) | |||||||||||||
SpO2 | 82% | ||||||||||||||
Bicarbonate | 11.0 mmol/L* | 23.0 – 29.0 | |||||||||||||
Base Excess | -12.0 mmol/L* | -2.0 – +2.0 | |||||||||||||
Sodium | 134 mmol/L* | 135 – 145 | |||||||||||||
Potassium | 2.9 mmol/L* | 3.5 – 5.0 | |||||||||||||
Chloride | 100 mmol/L | 95 – 105 | |||||||||||||
Glucose | 5.4 mmol/L | 3.5 – 6.0 |
a) Explain the acid base status, including your mathematical calculations where appropriate.
(20% marks)
b) List the most likely source of the metabolic acidosis in this patient. (10% marks)
c) List the most likely clinical diagnosis and underlying pathophysiology in this patient.
(10% marks)
d) Outline the advantages and disadvantages of a peripheral venous blood gas in critically ill patients.
(20% marks)
Not available.
"Including your mathematical calculations where appropriate"? I thought you'd never ask!
Now, this could well be a triple disorder (mixed high and normal anion gap metabolic acidosis as well as a respiratory alkalosis), but this is a venous gas, which really should not be used to assess compensation in a patient with such a terrible circulatory failure. The venous CO2 could be raised because of the extremely poor cardiac output, with an increased arteriovenous CO2 gradient, i.e. the respiratory alkalosis might be even more severe if you had an arterial sample.
Now:
b) List the most likely source of the metabolic acidosis in this patient.
They did not give us a lactate, but it's probably raised, and - not to cheat or anything - but on the same page, the next question about the same stem gives us a set of haematology values which is clearly demonstrating DIC. Thus, this looks like septic shock, and lactate is the most likely reason for the acidosis.
c) List the most likely clinical diagnosis and underlying pathophysiology in this patient.
The patient is falling apart from septic shock, in DIC, and there's "tissue resembling products of conception" in her vagina? What else could this be, if not septic abortion. There's barely anything to list. If it were not for those products, one could also consider toxic shock syndrome, eg. from a retained tampon. The pathophysiology is usually a polymicrobial infection by the normal flora of the vagina and endocervix.
d) The advantages and disadvantages of a peripheral venous blood gas in critically ill patients, in two minutes (because that's how long you have for this little 20% fragment), would have to be pretty brief:
Finkielman, Javier Daniel, et al. "The clinical course of patients with septic abortion admitted to an intensive care unit." Intensive care medicine 30.6 (2004): 1097-1102.
Stubblefield, Phillip G., and David A. Grimes. "Septic abortion." New England Journal of Medicine 331.5 (1994): 310-314.
Awasthi, Shilpi, Raka Rani, and Deepak Malviya. "Peripheral venous blood gas analysis: An alternative to arterial blood gas analysis for initial assessment and resuscitation in emergency and intensive care unit patients." Anesthesia, essays and researches 7.3 (2013): 355.
A 23-year-old male of Southeast Asian descent is admitted to the Emergency Department following an episode of syncope. He is currently resident in a medical research facility, taking part in a phase 1 trial of a novel anti-inflammatory agent. An extensive pre-trial health questionnaire did not reveal any concerns.
In the Emergency Department he is alert and comfortable with no respiratory distress, and noted to have an SpO2 of 83% on 15L O2 via a non-rebreathe mask.
His initial arterial blood gas results are shown below:
Parameter | Patient Value | Adult Normal Range | |||||||||||||
FiO2 | 0.9 | ||||||||||||||
pH | 7.52* | 7.35 – 7.45 | |||||||||||||
pO2 | 200 mmHg (26.3 kPa) | ||||||||||||||
pCO2 | 31.0 mmHg (4.1 kPa)* | 35.0 – 45.0 (4.6 – 6.0) | |||||||||||||
SaO2 | 100% | ||||||||||||||
Hb | 118 g/L* | 135 – 170 | |||||||||||||
FO2Hb | 90.6%* | 94.0 – 97.0 | |||||||||||||
FMetHb | 7.8%* | 0.0 – 1.5 | |||||||||||||
FCOHb | 2.1%* | 0.0 – 1.5 |
He has a baseline and repeat full blood count (at 24 hours), shown below:
Parameter | Patient Value | Adult Normal Range | |||||||||||||
On admission | At 24 hours | ||||||||||||||
Hb | 122 g/L | 77 g/L* | 120 – 160 | ||||||||||||
MCV | 91 | 92 | 80 – 100 | ||||||||||||
Platelets | 262 | 214 | 150 – 350 | ||||||||||||
WCC | 15.5 x 109/L* | 18.9 x 109/L* | 4.0 – 11.0 | ||||||||||||
Reticulocytes | - | 192 x 109/L* | 20 – 100 | ||||||||||||
Mega/myelocytes | 0.19 x 109/L* | 0.7 x 109/L* | 0.00 – 0.06 | ||||||||||||
Nucleated RBC | 1.1 | 6.4 | |||||||||||||
Film | Blister (helmet) cells ++, bite cells ++, polychromasia Occasional Howell-Jolly bodies |
a) List three potential causes of the discrepancy between SpO2 and SaO2 in this patient.
(15% marks)
b) List the likely diagnosis and underlying aetiology suggested by his investigations.
(30% marks)
c) List the additional tests you would order. List the results you would expect from these tests.
(25% marks)
d) List three potential causes for the elevated MetHb. (15% marks)
e) List three potential causes for the elevated COHb. (15% marks)
Not available.
a)
b)
Southeast Asian? Haemolysis? Surely this must G6PD deficiency, the most common hereditary enzymopathy among people from that part of the world. How did this happen?
c) Additional tests you would order:
d) Three potential causes for the elevated MetHb are asked for, but it is not clear whether they asked for causes in this patient or in general. Noting that the first part of this question specifies "in this patient", one can only conclude that generic causes of methaemoglobinaemia are asked for. But then, it asks for three potential causes for the elevated MetHb, not just an elevated MetHb. What are we to make of this?.. To be safe, the following differentials were tailored to the case scenario:
e) Three potential causes for the elevated COHb:
Beutler, Ernest. "G6PD deficiency." Blood 84.11 (1994): 3613-3636.
Frank, Jennifer E. "Diagnosis and management of G6PD deficiency." American family physician 72.7 (2005): 1277-1282.
Howes, Rosalind E., et al. "G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map." PLoS medicine 9.11 (2012): e1001339.
Luzzatto, Lucio, and Elisa Seneca. "G6 PD deficiency: a classic example of pharmacogenetics with on‐going clinical implications." British journal of haematology 164.4 (2014): 469-480.
Clark, Byron B., Robert W. Morrissey, and Dorothy Blair. "Relation of methemoglobin to hemolysis." Blood 6.6 (1951): 532-543.
Ata, Fateen, et al. "Favism Induced Methemoglobinemia in G6DP Deficient Patients: Case Series and Review of Literature." Blood 136.1 (2020): 11-12.
Jaffe, Todd A., et al. "Acute and delayed toxicity from co-ingestion of methylene chloride and methanol." Toxicology communications 3.1 (2019): 79-84.