Aldosterone and ADH in the distal nephron
Two hormones act on the same stretch of tubule but do different jobs. Aldosterone moves sodium in and potassium and hydrogen out; ADH only opens water channels.
Chapters (10)
Describe how aldosterone and ADH act in the distal nephron, and predict what happens to sodium, potassium, hydrogen and water.
The short version
- Principal cells reabsorb sodium, secrete potassium and handle water; type A intercalated cells secrete hydrogen into the urine.
- Aldosterone raises ENaC and the sodium–potassium pump, so sodium goes in and, through the lumen-negative voltage, potassium and hydrogen go out.
- Too much aldosterone gives sodium retention, hypertension, low potassium and metabolic alkalosis; too little gives the reverse: high potassium and a normal anion gap acidosis.
- ADH acts through the V2 receptor, cAMP and aquaporin-2 to let water leave the collecting duct; without ADH the duct turns waterproof.
- The amount of sodium excreted barely changes with ADH, because sodium balance is aldosterone's job.
Aldosterone and ADH in the distal nephron: one hormone, one stretch of tubule
A man has a blood pressure of 160/98, a potassium of 2.9, a bicarbonate of 33 and a low renin. One hormone, acting on one stretch of tubule, can explain all of it.
This lesson covers aldosterone and ADH in the distal nephron: how each acts, and how to predict what happens to sodium, potassium, hydrogen and water. Last time, the countercurrent system built a salty medulla. That gradient is useless unless the collecting duct lets water follow it. Earlier in the series, potassium shifting between cells and blood was covered; today is the kidney's side, how much leaves in the urine.
Two cell types in the distal nephron
| Cell type | Job |
|---|---|
| Principal cell | Reabsorbs sodium, secretes potassium, and handles water |
| Type A intercalated cell | Handles acid and base; secretes hydrogen into the urine |
Keep these two apart. Aldosterone's work is mostly in the principal cell, with a knock-on effect on the type A cell. ADH acts on the principal cell.[3][1][4]
Aldosterone in the principal cell: ENaC and the sodium–potassium pump
Aldosterone is a steroid, so it enters the principal cell and binds the mineralocorticoid receptor. The receptor turns on genes, over hours, for more sodium channels and more sodium–potassium pumps.[2][1]
- The sodium channel, ENaC, sits on the apical membrane, facing the urine.
- The sodium–potassium pump sits on the basolateral membrane, facing the blood.
- Sodium slides in through ENaC, and the pump sends it into the blood.
The key step: the lumen-negative voltage drives K⁺ and H⁺ secretion
Positive charge leaves the lumen as sodium enters, so the lumen becomes electrically negative. That negative voltage pulls potassium out through ROMK channels on the apical membrane.[1][3][6]
It also makes it easier for type A intercalated cells to pump hydrogen out with their H⁺-ATPase.[3]
Net result: aldosterone gives sodium in, potassium and hydrogen out.[2]
| State | Sodium | Potassium | Acid–base |
|---|---|---|---|
| Too much aldosterone | Retention, hypertension | Low | Metabolic alkalosis |
| Too little aldosterone | Reverse | High | Normal anion gap acidosis |
The opening patient, with hypertension, low potassium and a high bicarbonate, fits the excess pattern.
ADH: V2 receptor, cAMP and aquaporin-2
ADH binds the V2 receptor on the basolateral side of the principal cell.[4][5]
- ReceptorThe V2 receptor couples to a stimulatory G protein.
- Second messengerThat raises cAMP and activates protein kinase A.
- Channel insertionThe kinase phosphorylates aquaporin-2, and vesicles carrying it fuse with the apical membrane.
- Water crossesWater enters through aquaporin-2 and leaves through aquaporins 3 and 4 on the basolateral side.
When ADH falls, aquaporin-2 is pulled back inside and the duct turns waterproof. This step reclaims about 10 percent of the filtered water.[4][5]
Predicting water and sodium handling
Fluid reaches the late distal tubule at about 100 mOsm/kg. The medullary interstitium reaches about 1200.
- With ADH: aquaporin-2 is in place, water leaves, and urine climbs toward 1200.
- Without ADH: almost no water leaves, and urine stays near 100 or lower.
- Sodium: the amount excreted barely changes in either case, because sodium balance is aldosterone's job.
Practice question
Original · USMLE styleA 66-year-old man with a 20-year history of type 2 diabetes mellitus and chronic kidney disease comes for a routine follow-up visit. He has no symptoms. He takes no potassium supplements and no medication that affects the renin-angiotensin-aldosterone system. Venous blood studies show:
| Na⁺ | 135 mEq/L |
|---|---|
| K⁺ | 5.8 mEq/L |
| Cl⁻ | 108 mEq/L |
| HCO₃⁻ | 19 mEq/L |
| Plasma renin activity | low |
| Plasma aldosterone | low |
| Arterial pH | 7.32 |
| Anion gap | normal |
Common questions
What does aldosterone do in the distal nephron?
It binds the mineralocorticoid receptor in the principal cell and, over hours, raises ENaC and the sodium–potassium pump. Sodium goes in, and the resulting lumen-negative voltage pulls potassium and hydrogen out.
How does aldosterone cause potassium and hydrogen secretion?
Sodium entry through ENaC leaves the lumen electrically negative. That voltage pulls potassium out through ROMK and makes it easier for type A intercalated cells to pump hydrogen out with their H⁺-ATPase.
What happens with too much or too little aldosterone?
Too much gives sodium retention, hypertension, low potassium and metabolic alkalosis. Too little gives the reverse: high potassium and a normal anion gap acidosis.
How does ADH work on the collecting duct?
ADH binds the V2 receptor, which raises cAMP and activates protein kinase A. The kinase phosphorylates aquaporin-2, which fuses with the apical membrane so water can leave the duct.
What happens when ADH falls?
Aquaporin-2 is pulled back inside and the duct turns waterproof. Almost no water leaves, and urine stays near 100 mOsm/kg or lower.
Transcript
Read the full narration, by chapter668 words
0:00One hormone, one tubule
A man with blood pressure 160 over 98. His potassium is 2.9, his bicarbonate is 33, and his renin is low. One hormone, acting on one stretch of tubule, can explain all of it. Today: describe how aldosterone and ADH act in the distal nephron, and predict what happens to sodium, potassium, hydrogen and water. First, the mental model.
0:25The mental model
Last time, the countercurrent system built a salty medulla. That gradient is useless unless the collecting duct lets water follow it. And earlier, we saw potassium shift between cells and blood. Today is the kidney's side: how much leaves in the urine. Two cell types matter here.
0:44Two cell types
Principal cells reabsorb sodium, secrete potassium, and handle water. Intercalated cells handle acid and base, and the type A cell secretes hydrogen into the urine. Start with aldosterone.
0:58Aldosterone in the principal cell
It is a steroid, so it enters the principal cell and binds the mineralocorticoid receptor. That receptor turns on genes, over hours, for more sodium channels and more sodium potassium pumps. The sodium channel, called EN a C, sits on the apical membrane, facing the urine. The pump sits on the basolateral membrane, facing the blood. Sodium slides in through EN a C, and the pump sends it into the blood. Now the key step.
1:29The key step: lumen voltage, K+ and H+ secretion
Positive charge leaves the lumen, so the lumen becomes electrically negative. That negative voltage pulls potassium out through ROMK channels on the apical membrane. It also makes it easier for type A intercalated cells to pump hydrogen out with their H plus ATPase. So aldosterone: sodium in, potassium and hydrogen out. Too much aldosterone gives sodium retention,
1:56Too much, too little aldosterone
hypertension, low potassium and a metabolic alkalosis. That fits our patient. Too little gives the reverse: high potassium and a normal anion gap acidosis.
2:10ADH: V2 receptor, cAMP, aquaporin-2
Now ADH. It binds the V two receptor on the basolateral side of the principal cell. That receptor couples to a stimulatory G protein, which raises CAMP and activates protein kinase A. The kinase phosphorylates aquaporin two, and vesicles carrying it fuse with the apical membrane. Water enters through aquaporin two, and leaves through aquaporins three and four on the basolateral side. When ADH falls, aquaporin two is pulled back inside, and the duct turns waterproof. This step reclaims about 10% of the filtered water. So ADH opens water channels, and aldosterone drives sodium, potassium and hydrogen. Two hormones, two jobs. Let's predict.
2:59Predicting water and sodium
Fluid reaches the late distal tubule at about 100 milliosmoles per kilogram. The medullary interstitium reaches about 1200. With ADH, aquaporin two is in place, water leaves, and urine climbs toward 1200. Without ADH, almost no water leaves, and urine stays near 100 or lower. The amount of sodium excreted barely changes in either case, because sodium balance is
3:26Practice question
aldosterone's job. Your turn. A 66-year-old man has long-standing type two diabetes and chronic kidney disease. Sodium is 135, potassium 5.8, chloride 108, bicarbonate 19. Renin and aldosterone are both low. Which best explains his potassium and bicarbonate? A, increased EN a C insertion. B, less sodium entry through EN a C. C, impaired aquaporin two insertion. D, increased ROMK expression. E, loss of the chloride bicarbonate exchanger in type A cells. Pause here and decide. A is out: more EN a C would deepen the negative voltage and cost potassium, giving low potassium. C is out: that affects water, not potassium or bicarbonate. D is out: more ROMK would secrete more potassium, so the level would fall. E is out: that is a primary acid secretion defect, and it does not explain low aldosterone or the high potassium. So the answer is B: with low aldosterone, less sodium enters, the lumen is less negative, and potassium and hydrogen are both retained. Three things to keep.
4:52High-yield recap and next lesson
One: aldosterone raises EN a C and the pump, making sodium in, potassium and hydrogen out. Two: ADH, through V two, CAMP and aquaporin two, lets water leave the duct. Three: too much aldosterone gives low potassium and alkalosis, too little gives the reverse. Next up: diuretics by nephron segment.
Sources
Numbers in the text, e.g. [1], point here- Pearce D, et al. Pflugers Arch 2022. doi:10.1007/s00424-022-02732-5
- Tsilosani A, et al. Front Physiol 2022;13:770375.
- Rodriguez-Soriano J. J Am Soc Nephrol 2002. doi:10.1097/01.ASN.0000023430.92674.E5
- Vukicevic T, et al. Front Pharmacol 2016;7:23.
- Kharin S, Klussmann E. J Physiol 2024. doi:10.1113/JP284100
- eClinPath: Sodium and potassium transport in principal cells.
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. Nephron icon: "nephron 2d" by EmilyADaniel (bioicons.com), CC0 1.0 (https://creativecommons.org/publicdomain/zero/1.0/); recoloured, outlined, resized. All other diagrams are original (code-drawn). Example lab values are illustrative.
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-REN-028.
For exam study only, not medical advice. Read the medical disclaimer.
In this series
Playlist on YouTube- EP 01GFR and Starling forces at the glomerulus5:25
- EP 02Afferent vs efferent arteriole: GFR, RPF and filtration fraction5:16
- EP 03Renal clearance: inulin, creatinine and PAH5:20
- EP 04Glucose transport maximum, splay and SGLT24:55
- EP 05Countercurrent multiplier: how the kidney concentrates urine5:02
- EP 06Aldosterone and ADH in the distal nephron5:20
- EP 07Diuretics by nephron segment: loop, thiazide and more5:53
- EP 08RAAS explained: renin, angiotensin II and aldosterone5:23