Question 21.1

Angoff score
6.70
Highest mark
9.25
Pass rate
??
Other SAQs in this topic:
Other SAQs in this paper:

A 51-year-old patient presents with a decreased conscious state, Glasgow Coma Scale (GCS) 12, confusion and myoclonus. The patient is on treatment for a seizure disorder. The CT brain scan shows no acute intracranial abnormality.
The investigations are as follows:

Parameter

Patient Value          

Adult Normal Range

Sodium

138 mmol/L

135 – 145

Potassium

4.1 mmol/L

3.5 – 5.2

Bicarbonate

18 mmol/L*

22 – 32

Urea

14.2 mmol/L*

3.0 – 8.0

Creatinine

210 mmol/L*

45 – 90

Bilirubin

54 mmol/L*

< 20

Alanine transferase

2710 U/L*

< 35

Aspartate transferase

1365 U/L*

< 35

Alkaline phosphatase

103 U/L

30 – 110

g-Glutamyl transferase       

67 U/L*

< 40

Albumin

37 g/L

35 – 50

Protein

61 g/L

60 – 80

Ammonia

156 mmol/L*

< 50

a) List four possible causes of the hyper-ammonaemia in this patient. (4 marks)

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College answer

Syllabus topic/section:

2.1.6 Gastrointestinal Intensive Care / Acute hepatic failure: L1
2.1.5 Renal Intensive Care / Acid base and electrolyte disorders: L1
2.1.11 Haematological and Obstetric Intensive Care / Anaemia: L1
2.1.12 Obstetric Intensive Care: / Physiological change related to pregnancy: L1

Discussion:  

This was a repeat data interpretation question. Surprisingly the pass rate was low for this question. Lower scores were associated with not being specific about causes of hyperammonemia, but rather listed causes of hepatic dysfunction. A lack of synthesis of findings was also a feature of the answers failing to reach the standard required.

Discussion

This was indeed a repeat of  Question 9.1 from the first paper of 2017. That time, the college left us with a model answer, which looked like this:

  • Liver failure
  • Anti-epileptic drugs – Sodium valproate and Carbamazepine
  • Other drugs / toxins eg paracetamol, salicylates, mushrooms
  • Urosepsis with urea-splitting organisms e.g. Klebsiella, Proteus
  • Urea-cycle disorders (Patients with high ammonia from drugs or urosepsis usually have undiagnosed mild disorders of urea-cycle metabolism)

Causes of hyperammonaemia more broadly could be any of the following:

Pre-analytical error

  • Prolonged pre-transport time
  • Room temperature storage of sample

Increased substrate for ammoniagenesis

  • Excess protein catabolism:
    • Essential amino acid deficiency
    • Primary dietary carnitine deficiency
    • Steroids
    • Immobility
    • Severe exercise
    • Increased tissue turnover, eg haematological malignancy
  • Excess protein intake:
    • Weird diet
    • Parenteral nutrition

Bypass of normal metabolism

  • TIPS procedure
  • Portosystemic shunts

Acquired urea cycle defects

  • Fulminant hepatitis of any cause
  • Reye's syndrome
  • Drugs, eg. glycine or valproate

Congenital urea cycle defects

  • Inherited urea cycle defects
  • Organic aciduria
  • Fatty acid oxidation defects

Excess of exogenous ammonia

  • Ammonium chloride therapy
  • Excess generation of ammonia:
    • Gastric bypass
    • Urease-producing organisms
    • UTI

Reabsorption of excreted ammonia

  • Distal renal tubular acidosis
  • Ureteric diversion
  • Urinary tract infections
  • Vesicoureteric reflux
  • Bladder perforation

References

Conway, Edward Joseph, and Robert Cooke. "Blood ammonia." Biochemical Journal 33.4 (1939): 457.

Shambaugh, G. E. "Urea biosynthesis I. The urea cycle and relationships to the citric acid cycle." The American journal of clinical nutrition 30.12 (1977): 2083-2087.

McDermott Jr, William V., Raymond D. Adams, and Athol G. Riddell. "Ammonia metabolism in man." Annals of surgery 140.4 (1954): 539.

Hashim, Ibrahim A., and Jennifer A. Cuthbert. "Elevated ammonia concentrations: Potential for pre-analytical and analytical contributing factors." Clinical biochemistry 47.16 (2014): 233-236.

Clay, Alison S., and Bryan E. Hainline. "Hyperammonemia in the ICU." CHEST Journal 132.4 (2007): 1368-1378.

Weng, Te-I., Frank Fuh-Yuan Shih, and Wen-Jone Chen. "Unusual causes of hyperammonemia in the ED." The American journal of emergency medicine 22.2 (2004): 105-107.

Hawkes, N. D., et al. "Non-hepatic hyperammonaemia: an important, potentially reversible cause of encephalopathy." Postgraduate medical journal 77.913 (2001): 717-722.

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