New bicarbonate: how the kidney excretes acid with ammonium
The kidney reclaims the bicarbonate it filters, but that never makes new bicarbonate. Only excreting acid does, on two urinary buffers: titratable acid and ammonium.
Chapters (10)
Explain how the proximal tubule reclaims filtered HCO₃⁻ (about 80% of it, with no new HCO₃⁻), how new HCO₃⁻ is made when acid is excreted, as titratable acid (H⁺ secreted by the alpha-intercalated cell) or as ammonium (from glutamine metabolism in the proximal tubule), and why ammonium is the adjustable buffer in chronic acidosis.
The short version
- Reclaiming filtered bicarbonate, about 80% of it in the proximal tubule, makes no new bicarbonate; only excreting acid does.
- Each H⁺ excreted on a urinary buffer adds one new HCO₃⁻ to the blood.
- Titratable acid (mainly phosphate, 10–40 mEq/day) is capped by the phosphate you filter.
- Ammonium is the adjustable buffer: 30–40 mEq/day normally, over 200 mEq/day in chronic acidosis, but it takes days to ramp up.
- Net acid excretion = titratable acid + NH₄⁺ − urinary HCO₃⁻, and in a steady state it matches the acid you make.
The puzzle: acid you can't breathe out
Every day you make about 70 mEq of acid that you cannot breathe out.[1][3] The kidney has to get rid of it, and the way it does so is the way it makes new bicarbonate.
The obvious route does not work. Even the most acidic urine, pH 4.5, holds only about 0.03 mEq of free H⁺ per litre.[1][3]
- Free H⁺ at pH 4.5 ≈ 0.03 mEq/L
- Daily acid ≈ 70 mEq
- 70 ÷ 0.03 → over 2,000 litres of urine a day
So the urine needs buffers. This lesson shows how the kidney reclaims bicarbonate, and how it makes new bicarbonate with titratable acid and ammonium.
The kidney's two jobs: reclaim bicarbonate, make new bicarbonate
The kidneys set the bicarbonate side of the pH ratio.[5][3] The daily acid, much of it sulfuric and phosphoric, is buffered, much of it by bicarbonate, and each H⁺ buffered uses one HCO₃⁻ up.[1][3]
- Reclaim: don't lose the bicarbonate you filter.
- Make new: replace the bicarbonate the acid used up.
Job one: proximal bicarbonate reabsorption
- Filtrate ≈ 180 L/day
- Plasma HCO₃⁻ ≈ 24 mEq/L
- 180 × 24 = 4,320 → over 4,000 mEq of HCO₃⁻ filtered a day
About 80% of it is reabsorbed in the proximal tubule.[1][4] Sources give figures from 70% to 90%.[1][3][4]
- H⁺ outThe cell swaps Na⁺ in for H⁺ out through the sodium–hydrogen exchanger (NHE3).[1][4]
- In the lumenCarbonic anhydrase on the brush border turns that H⁺ and filtered HCO₃⁻ into CO₂ and water.[1][4]
- Back to the bloodCO₂ enters the cell, where carbonic anhydrase rebuilds HCO₃⁻, which leaves across the basolateral side on a Na⁺–3HCO₃⁻ cotransporter. The H⁺ is recycled.[1][3]
One HCO₃⁻ vanishes from the lumen and one appears in the blood: reclaimed, not new, and no acid has left the body.[3][5]
Later segments, about 15% in the thick ascending limb and the rest further on, take up nearly all of what is left, so normal urine is almost bicarbonate free.[1][3]
Job two: new bicarbonate from the alpha-intercalated cell
New bicarbonate is made in two places. One is the alpha-intercalated cell of the collecting duct, described here.[1][3] The other, tied to ammonium, is the proximal tubule (see below).[2]
- Inside the cell, CO₂ and water make H⁺ and HCO₃⁻ (carbonic anhydrase).
- A proton pump (H⁺-ATPase) pushes the H⁺ into the urine.
- The HCO₃⁻ goes to the blood in exchange for Cl⁻.
That bicarbonate is brand new, as long as its H⁺ leaves in the urine. Each H⁺ excreted on a buffer adds one new HCO₃⁻ to the blood.[3][1] But free H⁺ cannot carry the load, so the urine needs buffers.
Titratable acid and ammonium: the two urinary buffers
Titratable acid is mainly filtered phosphate picking up H⁺ (HPO₄²⁻ + H⁺ → H₂PO₄⁻, pK 6.8), normally 10–40 mEq a day.[3][1] It is limited mostly by the phosphate you filter, so it can rise only about 2–3 fold.[5][1]
Ammonium is the buffer the kidney can turn up. The proximal tubule breaks each glutamine into two NH₄⁺ and two new HCO₃⁻. The HCO₃⁻ goes to the blood; the ammonia heads for the urine, where it enters the collecting-duct lumen as NH₃ and is trapped there as NH₄⁺ by secreted H⁺.[2][3]
| Titratable acid | Ammonium (NH₄⁺) | |
|---|---|---|
| What it is | Mainly filtered phosphate + H⁺ | Made from glutamine in the proximal tubule |
| Normal excretion | 10–40 mEq/day | 30–40 mEq/day |
| In chronic acidosis | Rises only ~2–3×, capped by filtered phosphate | Can pass 200 mEq/day, over days |
| Role | Supply-limited buffer | Adjustable buffer |
Chronic acidosis and net acid excretion
Normally you excrete 30–40 mEq of ammonium a day. In chronic acidosis that can pass 200 mEq a day, but it takes days to ramp up, one reason renal compensation is slow.[2][3][1] Maximal renal adaptation to an acid load takes about 3–5 days.[1]
In a steady state, net acid excretion (the new HCO₃⁻ made) matches the acid you make each day.
That closes the loop from the opening puzzle: the daily acid leaves bound to phosphate and as ammonium, and every H⁺ that leaves this way puts one new HCO₃⁻ back in the blood.[3][1]
Practice question
Original · USMLE styleA 34-year-old man comes to the physician because of 5 days of profuse watery diarrhea that began after a trip abroad. He has had no vomiting and takes no medications. Pulse is 104/min and blood pressure is 108/68 mm Hg. Mucous membranes are dry. Laboratory studies show:
| Serum Na⁺ | 136 mEq/L |
|---|---|
| Serum K⁺ | 3.2 mEq/L |
| Serum Cl⁻ | 114 mEq/L |
| Serum HCO₃⁻ | 14 mEq/L |
| Arterial pH | 7.31 |
| Arterial PCO₂ | 29 mm Hg |
| Urine pH | 5.0 |
Common questions
Does proximal bicarbonate reabsorption make new bicarbonate?
No. It reclaims filtered HCO₃⁻: one HCO₃⁻ leaves the lumen and one enters the blood, and no acid leaves the body. New bicarbonate is made only when acid is excreted.
What is titratable acid?
H⁺ excreted on filtered buffers, mainly phosphate (HPO₄²⁻ + H⁺ → H₂PO₄⁻). It is normally 10–40 mEq a day and is limited by the phosphate you filter.
Why is ammonium more important than titratable acid in chronic acidosis?
The kidney can turn ammonium production up: excretion rises from 30–40 mEq a day to over 200. Titratable acid rises only about 2–3 fold because it is capped by filtered phosphate.
What is the formula for net acid excretion?
Net acid excretion = titratable acid + NH₄⁺ − urinary HCO₃⁻. In a steady state it matches the acid you make each day.
Why can't the kidney just excrete free H⁺?
Even at the minimum urine pH of 4.5, a litre holds only about 0.03 mEq of free H⁺, so excreting about 70 mEq of daily acid that way would take over 2,000 litres of urine.
Transcript
Read the full narration, by chapter698 words
0:00The puzzle: 70 mEq of acid a day, 0.03 mEq/L of free H⁺
Every day, you make about 70 milliequivalents of acid you can't breathe out. Even your most acidic urine, pH 4.5, holds just 0.03 mEq of free hydrogen per litre. So to excrete that acid free, you'd need over 2000 litres of urine a day.
0:20The kidney's two jobs: reclaim vs make new HCO3⁻
Today: how the kidney reclaims bicarbonate, and makes new bicarbonate with titratable acid and ammonium. Remember, the kidneys set the bicarbonate side of the ratio. That daily acid, much of it sulfuric and phosphoric, is buffered, much of it by bicarbonate, and each hydrogen ion buffered uses one up. So the kidney has two jobs: don't lose the bicarbonate you filter, and replace what the acid used. But here's the catch: reclaiming bicarbonate never makes new bicarbonate. Only excreting acid does.
0:56Job 1: proximal HCO3⁻ reclamation (NHE3, carbonic anhydrase)
Job one. You filter about 180 litres a day, at a bicarbonate of about 24. That's over 4000 milliequivalents, and about 80% is reabsorbed in the proximal tubule. The cell swaps sodium in for hydrogen out, through the sodium-hydrogen exchanger. In the lumen, carbonic anhydrase turns that hydrogen and filtered bicarbonate into carbon dioxide and water. Carbon dioxide enters the cell, where bicarbonate is rebuilt and sent into the blood. One bicarbonate vanishes from the lumen, one appears in the blood: reclaimed, not new, and no acid has left.
1:37Acetazolamide and the rest of the nephron
Block carbonic anhydrase with acetazolamide, and bicarbonate spills into the urine: the normal gap acidosis from lesson 2. Later segments take up nearly all the rest, so normal urine is almost bicarbonate free.
1:53Job 2: making new HCO3⁻, site 1: the alpha-intercalated cell
Job two, making new bicarbonate, happens in two places. The first is the alpha intercalated cells of the collecting duct. Inside the cell, carbon dioxide and water make hydrogen and bicarbonate. A proton pump pushes the hydrogen into the urine, and the bicarbonate goes to the blood, in exchange for chloride. That bicarbonate is brand new, as long as its hydrogen leaves in the urine.
2:20Buffer 1: titratable acid (phosphate)
But free hydrogen can't carry the load, so the urine needs buffers. Buffer one is titratable acid: mainly filtered phosphate picking up hydrogen, normally 10 to 40 milliequivalents a day. But it's limited by how much phosphate you filter, so it can't rise nearly as much as the next buffer.
2:41Buffer 2: ammonium, and the liver twist
Buffer two is ammonium, and this one the kidney can turn up. The proximal tubule breaks each glutamine into two ammonium ions and two new bicarbonates. The bicarbonate goes to the blood; the ammonium heads for the urine, trapped there by secreted hydrogen. Here's the twist: that bicarbonate only counts if the ammonium is excreted. If it returns to the blood, the liver makes urea from it, and that uses the bicarbonate up again.
3:10Ammonium in chronic acidosis and net acid excretion
Normally, you excrete 30 to 40 milliequivalents of ammonium a day. In chronic acidosis, that can pass 200, but it takes days to ramp up, one reason renal compensation is slow. So net acid excretion is titratable acid plus ammonium, minus urinary bicarbonate, and in a steady state it matches the acid you make.
3:34Practice question
Your turn. A 34-year-old man has 5 days of watery diarrhea. Sodium 136, potassium 3.2, chloride 114, bicarbonate 14. pH 7.31, PaCO2 29, urine pH 5. Which renal process accounts for most of the increase in new bicarbonate added to his blood? A, proximal bicarbonate reabsorption. B, free hydrogen ion excretion. C, hydrogen bound to filtered phosphate. D, glutamine metabolism with ammonium excretion. E, bicarbonate secretion by type B intercalated cells. Pause and decide. A is out: it reclaims bicarbonate, but makes none. B is out: at a urine pH of five, a litre carries just a hundredth of a milliequivalent of free hydrogen. E is out: secreting bicarbonate would worsen his acidosis. C is real, but it rises far less, capped by the phosphate he filters. So the answer is D: ammonium excretion rises several-fold, and each ammonium excreted leaves a new bicarbonate behind.
4:55High-yield recap and next lesson
Three things to keep. One: reclaiming filtered bicarbonate, about 80% of it in the proximal tubule, makes none new. Two: each hydrogen excreted on a buffer adds one new bicarbonate to the blood. Three: ammonium is the adjustable buffer, so it does most of the extra work in acidosis. Next, we sort the high anion gap acidoses by the acid behind each one.
Sources
Numbers in the text, e.g. [1], point here- Hamm LL, Nakhoul N, Hering-Smith KS. Acid-Base Homeostasis. Clin J Am Soc Nephrol 2015;10(12):2232–42. doi:10.2215/CJN.07400715. pmc.ncbi.nlm.nih.gov/articles/PMC4670772/
- Weiner ID, Verlander JW. Renal Ammonia Metabolism and Transport. Compr Physiol 2013;3(1):201–20. pmc.ncbi.nlm.nih.gov/articles/PMC4319187/
- Madias NE. Introduction to Acid/Base Physiology. Tufts University School of Medicine OpenCourseWare, Renal Pathophysiology. oerafrica.org/FTPFolder/Website%20Materials/Health/OER%20Sampler/Univ%20Botswana%20Medical%20School/resources/TUFTS%20OPENCOURSEWARE/Renal%20Pathophysiology/Intro%20to%20Acid%20Base%20Physiology%5D.pdf
- Yartsev A. Renal regulation of acid-base balance. Deranged Physiology, CICM primary ch. 016. derangedphysiology.com/main/cicm-primary-exam/required-reading/renal-system/Chapter%20016/renal-regulation-acid-base-balance
- Lewis JL III. Acid-Base Regulation; Metabolic Acidosis. MSD Manual Professional Version (2025). msdmanuals.com/professional/endocrine-and-metabolic-disorders/acid-base-regulation-and-disorders/acid-base-regulation · msdmanuals.com/professional/endocrine-and-metabolic-disorders/acid-base-regulation-and-disorders/metabolic-acidosis
- Alam P et al. Am J Physiol Renal Physiol 2020;319(3):F366–F379. pmc.ncbi.nlm.nih.gov/articles/PMC7509283/
- OpenAnesthesia. Acetazolamide. openanesthesia.org/acetazolamide
- Kandasamy N et al. Life-threatening metabolic alkalosis in Pendred syndrome. Eur J Endocrinol 2011;165(1):167–70. pmc.ncbi.nlm.nih.gov/articles/PMC3118492/
The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.
Image credits. Illustrations: Servier Medical Art (smart.servier.com), licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/); adapted (recoloured, outlined, resized): nephron, liver. All other diagrams are original.
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-REN-021.
For exam study only, not medical advice. Read the medical disclaimer.
In this series
Playlist on YouTube- EP 01ABG interpretation, made simple5:35
- EP 02Anion gap explained: high vs normal gap metabolic acidosis5:25
- EP 03Winters' formula: the expected PaCO₂ in metabolic acidosis5:10
- EP 04Delta ratio: find the hidden second acid–base disorder5:09
- EP 05New bicarbonate: how the kidney excretes acid with ammonium5:23
- EP 06High anion gap metabolic acidosis causes, sorted by the anion5:54
- EP 07Osmolar gap: how toxic alcohols hide from the anion gap5:31
- EP 08Urine anion gap: telling diarrhea from RTA5:33
- EP 09Renal tubular acidosis: tell RTA types 1, 2 and 4 apart5:24
- EP 10Metabolic alkalosis: generation, maintenance and urine chloride5:30
- EP 11Vomiting metabolic alkalosis: why the urine turns acid5:36
- EP 12Bartter vs Gitelman: NKCC2, NCC and urine calcium5:21
- EP 13Respiratory acidosis compensation: acute vs chronic5:22
- EP 14Respiratory alkalosis compensation: acute vs chronic5:33
- EP 15Metabolic alkalosis compensation: the expected PaCO₂5:12
- EP 16Salicylate poisoning acid-base: a classic mixed disorder5:31
- EP 17Type A vs type B lactic acidosis: split it by mechanism5:33
- EP 18DKA anion gap explained: from high gap to hyperchloraemic acidosis5:42
- EP 19Acidosis and hyperkalemia: how pH shifts potassium5:43
- EP 20ABG interpretation in 6 steps: the acid-base algorithm5:32
- EP 21Acid-base practice cases: three ABG vignettes, one algorithm5:44