Question 12

Describe the role of the kidneys in the excretion of non-volatile acid.

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College Answer

This is a complex but essential area of physiology for intensive care practice. It was expected 
candidates would indicate that non-volatile acids are those not able to eliminated by the lungs
(lactate, sulphate, phosphate and ketone bodies). The kidney plays a central role via bicarbonate 
(resorbing filtered bicarbonate and generating “new” bicarbonate = acid excretion). It was 
expected candidates could detail the processes in various parts of the renal tubules and the role 
or urinary buffers (dibasic phosphate and ammonia). 
While a number of candidates were able to provide some of the details of ion transports in the 
kidney, few showed understanding of the overarching concepts of the proximal bicarbonate 
reabsorption being necessary to allow the distal acid excretion.


The college answer has a few problems. For instance, ammonia is not a buffer, as its pKa is 9.15, and at physiological pH 99% of it is present in the form of ammonium (NH4+).  Also, it is unclear what was meant by "generating “new” bicarbonate = acid excretion". One becomes concerned with statements like this, because there is a real threat that the examiner marking your work may not be able to recognise a correct answer. With a pass rate this worrying (27%),  it would have been interesting to see exactly what elements were considered essential in the marking rubric. Without any further complaining, here is an answer which would probably satisfy some of the examiners, even though it probably violates the maximum possible 10-minute word count of a person writing by hand:

  • Non-volatile acids produced in the course of metabolism are:
    • Lactate
    • Ketones
    • Phosphate
    • Sulfate
    • Urate
    • Hippurate
  • Non-volatile acid handling in the tubule:
    • These are filtered freely in the proximal tubule
    • A large fraction is then reabsorbed in the pars recta, as many of these are essential metabolic substrates
    • The remaining fraction allows urine pH to be buffered
  • Contribution to acid-base regulation
    • Non-volatile acids buffer the pH of the urine, allowing more H+ to be excreted then would otherwise be possible
    • Phosphate is the most important of these buffers quantitatively
      • pKa of phosphate is 6.8
      • In the tubule it is present in two main forms, H2PO4- and HPO42-
      • With increased tubule acidity, HPO42- buffers H+ and produces H2PO4-, which is poorly absorbed
      • H2PO4- is then eliminated, taking  H+ with it. 
    • Other buffers include creatinine and citrate, which have a higher buffering capacity at low urine pH (around 5.0)
  • Excretion of ammonium is the most important mechanism of acid excretion
    • Ammonia (NH3) is produced in the kidney from the metabolism of glutamine, which also produces bicarbonate
    • In the proximal tubule, NH3 binds H+ in the lumen and becomes ammonium (NH4+)
    • Ammonium is then concentrated in the inner medulla by reabsorption in the thick ascending limb
    • Concentrated ammonium is then secreted in the collecting duct
    • This is quantitatively the most important mechanism of acid elimination 
    • Metabolism of glutamine can increase tenfold in response to metabolic acidosis


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McNamara, J., and L. Worthley. "Acid-base balance: part I. Physiology." Critical Care and Resuscitation 3 (2001): 181-187.

Atherton, John C. "Role of the kidney in acid–base balance." Anaesthesia & Intensive Care Medicine 16.6 (2015): 275-277.

Weiner, I. David, Jill W. Verlander, and Charles S. Wingo. "Renal acidification mechanisms." Core Concepts in the Disorders of Fluid, Electrolytes and Acid-Base Balance. Springer, Boston, MA, 2013. 203-233.

Madias, Nicolaos E., and Horacio J. Adrogué. "Cross-talk between two organs: how the kidney responds to disruption of acid-base balance by the lung." Nephron Physiology 93.3 (2003): p61-p66.

Hamm, L. Lee, Nazih Nakhoul, and Kathleen S. Hering-Smith. "Acid-base homeostasis." Clinical Journal of the American Society of Nephrology 10.12 (2015): 2232-2242.