I am working on a handout for a workshop on acid-base and electrolyte disorders. This entry is my attempt to explain renal ammonia physiology. I hope a few readers will critique my attempt.

Each day the average American creates 1 mEq/kg of acid which needs buffering. Most of the acid comes from protein. Our kidneys normally do all the buffering through 2 main systems – titratable and non-titratable acids Titratable acids (phosphates and sulfates) are relatively fixed in buffering capacity. Non-tritatable acids (ammonium – NH4+) does vary appropriately in patients having normally functioning kidneys. Thus, we adjust our buffering using ammonium.

If we cannot produce enough ammonium, then we develop a normal gap metabolic acidosis. Understanding the physiology of ammonium excretion helps us understand the possible problems.

1 (see figure) – in the proximal tubular cells, glutamine converts to alpha ketoglutarate to produce NH3 (ammonia). Ammonia goes into the tubule and converts to NH4+. Thus, as patients lose proximal tubular cells they may lose buffering capacity because they cannot make enough ammonia.

2 – in the ascending limb of the loop of Henle, NH4+ goes into the intersitium by means of the sodium potassium 2 chloride cotransporter (this is the site which loop diuretics block). The NH4+ then converts back to NH3 and becomes part of the countercurrent multiplier system. Thus the medullary part of the kidney has very high concentrations of NH3.

3 – in the distal tubule, we acidify the urine. Here NH3 diffuses into the distal tubule, converts back to NH4+, creating the desired buffer effect.

Renal acidosis (normal gap) can occur for 3 major reasons.

1. Distal RTA – inability to acidify the urine – cannot excrete the ingested acid if we cannot make mEq portions of NH4+ (which requires an acidified urine)

2. Type IV RTA – this one is interesting. The problem in type IV RTA is primarily hyperkalemia (most commonly called hyporenin/hypoaldo). Increased potassium levels inhibit the enzyme glutaminase which is responsible for the production of ammonia (see 1 in the figure). Thus if we correct the hyperkalemia, we usually resolve the acidosis.

3. The acidosis of CKD – two problems for these patients – decreased production of ammonia and decreased concentration in the medulla. As CKD worsens, the countercurrent mechanism does not function as efficiently, decreasing the concentrations of solutes in the medulla. Thus, less ammonia is available to enter the distal tubule for buffering.

I hope these explanations make sense. Please suggest any clarifications or ask any questions which will force me to do a better job explaining.

Thanks