Regarding regional citrate anticoagulation for continuous renal replacement therapy (CRRT):
a) What is the mechanism by which citrate provides anticoagulation? (20% marks)
b) What is the metabolic fate of the citrate? (10% mark)
c) What are the features of citrate toxicity? (30% marks)
d) What conditions may increase the risk of citrate toxicity? (20% marks)
e) What alternative(s) to citrate could you use in a patient with severe Heparin Induced Thrombocytopaenia (HIT)? (20% marks)
This question is virtually identical to Question 22 from the first paper of 2015, except the distribution of marks in 2021 was skewed, moving 10% of the marks from the metabolic fate of citrate and putting them into citrate toxicity. To the candidates, this is a signal that primary exam material is being de-emphasised.
What is the mechanism by which citrate provides anticoagulation?
Citrate is a calcium chelator, and by robbing the clotting cascade of its ionised calcium it disables the steps of the cascade in which calcium plays a role (many people dont realise that calcium used to be Factor IV). The following are clotting cascade proteins which require calcium to function:
So, 2, 7 9 and 10. Same as the Vitamin K-dependent factors.
What is the metabolic fate of the citrate?
The words "metabolic fate" are music to my ears.
In brief, citrate - in the course of its metabolism via the Krebs cycle - removes 3 H+ ions from the body, which has the equivalent effect of adding 3 HCO3- molecules. Thus, it is generally said that "citrate generates three bicarbonate molecules". It is true - its metabolism is the equivalent of buffering, and in excess citrate can cause a metabolic alkalosis. Thankfully, some of the citrate ends up being removed by the dialysis circuit, as it is a very small molecule.
What are the features of citrate toxicity?
Citrate toxicity - or rather, its biochemical features - is touched upon in the answer to Question 3.3 from the second paper of 2013.
In brief, the main features of citrate toxicity are as follows:
What conditions may increase the risk of citrate toxicity?
Citrate is mainly metabolised in the liver.
What alternative(s) to citrate could you use in a patient with severe HITS?
One might also mention using higher flow rates and pre-dilution as non-pharmacological means of increasing filter lifespan. In general, a massive list of strategies used to improve filter lifespan is also available somewhere around here, and it contains many options which don't involve citrate.
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