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.

(This blood gas is discussed in Question 23.1 )

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

 

Six hours later the patient remains on NIV, is conscious, reports feeling slightly better, feet remain cyanosed, BP 105/72 mmHg, HR 108 bpm, RR 30 breaths/min, urine output 10 – 20 mL/hr and the following biochemistry profile is obtained:

Parameter

Patient Value

Normal Adult Range

Sodium

139 mmol/L

135 – 145

Potassium

5.5 mmol/L*

3.5 – 5.2

Chloride

110 mmol/L

95

– 110

Bicarbonate

12 mmol/L*

22

– 32

Urea

20.0 mmol/L*

2.7 – 7.8

Creatinine

220 μmol/L*

70

– 120

Estimated glomerular filtration rate (eGFR)

25 mL/min/1.73 m2*

> 90

Anion gap

22 mmol/L*

8 – 18

Total protein

57 g/L*

60

– 80

Albumin

27 g/L*

35

– 50

Total bilirubin

24.9 μmol/L

< 25

Alkaline phosphatase (ALP)

81 IU/L

30

– 110

Alanine transaminase (ALT)

6138 IU/L*

< 65

Aspartate transaminase (AST)

10122 IU/L*

< 50

g-Glutamyl transferase (GGT)

88 IU/L

< 90

C-reactive protein (CRP)

22.5 mg/L*

< 8

b)  Give your interpretation of these findings. Include likely aetiologies.            (40% marks)

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College Answer

Increasing anion gap due to worsening renal impairment and possibly increasing lactate.

LFTs deranged with predominant finding of transaminitis. (This is likely to be associated with an increase in lactate).

Aetiologies

  • Liver ischaemia due to hypoperfusion
  • cardiac failure (poor output +/- liver congestion) severe sepsis with profound hypotension
  • other shock states e.g. obstructive thrombo-embolic disease
  • Drug related e.g. paracetamol (inadvertent or deliberate)
  • (NB Acute alcoholic hepatitis is unlikely with such a high AST)

Discussion

The following biochemical abnormalities are present in the second set of results:

  • High anion gap metabolic acidosis
  • Renal impairment (raised urea and creatinine)
  • Hypoalbuminaemia
  • Borderline raised bilirubin
  • Trivially elevated cholestatic liver enzymes
  • Massively elevated hepatic transaminases
  • A high AST to ALT ratio
  • Trivially elevated inflammatory markers

The raised transaminases are described as a "transaminitis" by the college, a term which has been in use since 1977, in spite of some authors referring to it as "made up and improper" (Stellpflug, 2011). The previous set of results from Question 23.1 demonstrated a raised lactate and severe acidaemia wioth a normal glucose and normal haemoglobin. From the list of causes of elevated transaminases, the following are relevant diferentials, and parenthesised comments as to why they are relevant:

  • Congestive heart failure (he has COPD: maybe the right heart?)
  • Portal vein thrombosis (past history of cancer)
  • Malignant infiltration (past history of cancer)
  • Drug overdose (this is always an option)
  • Viral hepatitis (this is always an option)
  • Fatty liver or NASH
  • Liver abscess (right lower lobe "infiltrate" may be sympathetic effusion)
  • α1-antitrypsin deficiency (the college has given a history of COPD, implying emphysema, but no history of any actual smoking)
  • Poor liver perfusion and ischaemia ("shock liver") - however, no history of profound hypotension

And then those things which this is not:

  • Alcoholic hepatitis (unlikely: no history of drinking and GGT is not elevated)
  • Pancreatitis (not a cholestatic picture)
  • Traumatic causes (no history of trauma)
  • Congenital issues, haemochromatosis, Wilson's disease (he's 70)

References

References

Stellpflug, Samuel J. "Transaminitis: The Lab Test That Has Inflammation…." Journal of Medical Toxicology 7.3 (2011): 252-253.

Johnston, David E. "Special considerations in interpreting liver function tests." American family physician 59 (1999): 2223-2232.

Limdi, J. K., and G. M. Hyde. "Evaluation of abnormal liver function tests." Postgraduate medical journal 79.932 (2003): 307-312.

Hoekstra, Lisette T., et al. "Physiological and biochemical basis of clinical liver function tests: a review." Annals of surgery 257.1 (2013): 27-36.