RAAS explained: renin, angiotensin II and aldosterone
The renin–angiotensin–aldosterone system explained step by step: three triggers for renin release, four jobs for angiotensin II, and what aldosterone does in the collecting duct.
Chapters (9)
Trace the triggers for renin release and the actions of angiotensin II and aldosterone on GFR, sodium handling and blood pressure.
The short version
- Renin comes from juxtaglomerular cells and is released by low afferent arteriolar pressure, low NaCl delivery to the macula densa, and sympathetic β₁ stimulation.
- Renin cuts angiotensinogen to angiotensin I; ACE, mostly on lung endothelium, makes angiotensin II.
- Angiotensin II constricts arterioles, constricts the efferent arteriole more than the afferent to keep GFR, raises proximal Na⁺–H⁺ exchange, ADH and thirst, and drives aldosterone release.
- Aldosterone acts on principal cells and intercalated cells: sodium and water are kept, potassium and hydrogen are lost.
- Excess aldosterone gives hypertension, low potassium and metabolic alkalosis; angiotensin II, pressure and macula densa NaCl switch renin off.
RAAS explained: why one narrowed artery raises blood pressure everywhere
A 24-year-old woman has a blood pressure of 176/108 mm Hg. Her potassium is 3.1 mmol/L and her bicarbonate is 32 mmol/L. One of her kidney arteries is narrowed. Why does her whole body become hypertensive?
The answer is the renin–angiotensin–aldosterone system (RAAS). This lesson follows it from the sensor in the kidney, through angiotensin II, to aldosterone in the collecting duct.[1][2]
Renin release: three triggers at the juxtaglomerular cells
Renin is made by juxtaglomerular cells in the wall of the afferent arteriole. Three things switch it on.[1][2][3]
- Low pressure in the afferent arteriole.
- Low NaCl delivery to the macula densa, at the start of the distal tubule.
- Sympathetic nerves acting on β₁ receptors.
The kidney releases renin whenever it senses low pressure or low salt, whether or not the body is truly dry. That is the key to the opening patient.
The RAAS cascade: angiotensinogen to angiotensin II
- Liver makes angiotensinogenThis is the substrate.
- Renin cuts it into angiotensin IRenin is an enzyme.
- ACE makes angiotensin IIAngiotensin-converting enzyme sits mostly on lung endothelium.
Renin is the controlled step: the cascade runs when the kidney releases it.[1][2][3]
Angiotensin II: four jobs, including protecting GFR
| Action | Effect |
|---|---|
| Systemic arteriolar vasoconstriction | Raises blood pressure |
| Efferent arteriole constricted more than the afferent | Holds glomerular pressure up when blood flow is low, so GFR is kept and the filtration fraction rises |
| Proximal tubule Na⁺–H⁺ exchange increased; ADH and thirst raised | More sodium and water retained |
| Adrenal cortex stimulated | Aldosterone is released |
The renal action is the one that is easy to forget. Tightening the efferent arteriole keeps glomerular pressure up, so filtration continues even when flow is low.[1][2][3]
Aldosterone: sodium kept, potassium and hydrogen lost
Aldosterone acts on the principal cells of the collecting duct. It increases the sodium channel ENaC, the Na⁺–K⁺ ATPase and the potassium channel. Sodium and water are kept, and potassium is lost.[1]
Aldosterone also increases H⁺-ATPase (proton pump) activity in the α-intercalated cells, so hydrogen is lost too.
The signature of excess aldosterone is therefore hypertension, low potassium and metabolic alkalosis. A high plasma potassium also stimulates aldosterone directly.
The brake on renin, and back to the patient
There is a brake. Angiotensin II, higher pressure and more salt at the macula densa all switch renin off.[2][3]
In the opening patient, a narrowed renal artery means low pressure beyond it. The kidney reads that as dryness and releases renin. Angiotensin II and aldosterone then push the body into hypertension, with potassium and acid loss: the low potassium and high bicarbonate.[1]
Worked example: an ACE inhibitor in bilateral renal artery stenosis
A 68-year-old man has both renal arteries narrowed and starts an ACE inhibitor.
- His kidneys depend on angiotensin II to keep the efferent arteriole tight
- The ACE inhibitor removes angiotensin II
- The efferent arteriole relaxes and glomerular pressure falls
- Creatinine rises from 1.0 to 1.9 mg/dL
Angiotensin II protects GFR when perfusion is low, so removing it can hurt.[1][2]
Practice question
Original · USMLE styleA 47-year-old man is brought to the emergency department after 3 days of vomiting and diarrhea. His blood pressure is 88/54 mm Hg and heart rate is 118/min. Mucous membranes are dry. Laboratory studies show:
| Blood urea nitrogen | 38 mg/dL |
|---|---|
| Serum creatinine | 1.6 mg/dL |
| Urine sodium | 8 mEq/L |
Common questions
What triggers renin release?
Three things: low pressure in the afferent arteriole, low NaCl delivery to the macula densa, and sympathetic stimulation of β₁ receptors on juxtaglomerular cells.
What does angiotensin II do to the kidney?
It constricts the efferent arteriole more than the afferent. This holds glomerular pressure up when blood flow is low, so GFR is kept and the filtration fraction rises.
What does aldosterone do?
It acts on principal cells to increase ENaC, the Na⁺–K⁺ ATPase and the potassium channel, so sodium and water are kept and potassium is lost. Aldosterone also increases proton pump activity in α-intercalated cells, so hydrogen is lost too.
Why can an ACE inhibitor raise creatinine?
Without angiotensin II the efferent arteriole relaxes and glomerular pressure falls. In bilateral renal artery stenosis this can lower GFR, and creatinine rises.
What are the signs of excess aldosterone?
Hypertension, low potassium and metabolic alkalosis.
Transcript
Read the full narration, by chapter657 words
0:00Hypertension from one narrowed kidney artery
A 24-year-old woman has a blood pressure of 176 over one-oh-eight. Her potassium is 3.1, and her bicarbonate is 32 millimoles per litre. One of her kidney arteries is narrowed, so why does her whole body become hypertensive? Today: trace what triggers renin release, and what angiotensin two and aldosterone do. Last time, diuretics worked on the distal nephron. Now we meet the hormones that control that same nephron.
0:31The sensor: three triggers for renin release
Start with the sensor. Renin comes from juxtaglomerular cells in the wall of the afferent arteriole. Three things switch it on. One: low pressure in the afferent arteriole. Two: low sodium chloride delivery to the macula densa, at the start of the distal tubule. Three: sympathetic nerves, acting on beta one receptors. The kidney releases renin whenever it senses low pressure or low salt, whether or not the body is truly dry.
1:02The cascade: angiotensinogen to angiotensin II
Now the cascade. The liver makes angiotensinogen. Renin, an enzyme, cuts it into angiotensin one. Angiotensin converting enzyme, mostly on lung endothelium, makes angiotensin two.
1:17Four jobs of angiotensin II (and GFR protection)
Angiotensin two has four jobs. First, it constricts arterioles everywhere, raising blood pressure. Second, in the kidney it constricts the efferent arteriole more than the afferent. That holds glomerular pressure up when blood flow is low, so GFR is kept, and the filtration fraction rises. Third, it increases sodium hydrogen exchange in the proximal tubule, and it raises ADH and thirst. Fourth, it makes the adrenal cortex release aldosterone.
1:51Aldosterone: sodium kept, potassium and hydrogen lost
Aldosterone acts on principal cells of the collecting duct. It increases the sodium channel EN a C, the sodium potassium AT Pase, and the potassium channel. Sodium and water are kept, and potassium is lost. Intercalated cells add proton pumps, so hydrogen is lost too. The signature of excess aldosterone: hypertension, low potassium, and metabolic alkalosis. A high plasma potassium also stimulates aldosterone directly.
2:23The brake, and back to the patient
And there is a brake. Angiotensin two, higher pressure, and more salt at the macula densa all switch renin off. Back to our patient. A narrowed renal artery means low pressure beyond it. The kidney reads that as dryness, releases renin, and the body is pushed into hypertension with potassium and acid loss.
2:45Worked example: ACE inhibitor in bilateral stenosis
Now a drug. A 68-year-old man with both renal arteries narrowed starts an ACE inhibitor. Without angiotensin two, the efferent arteriole relaxes, glomerular pressure falls, and his creatinine rises from 1.0 to 1.9. Angiotensin two protects GFR when perfusion is low, so removing it can hurt.
3:09Practice question
Your turn. A 47-year-old man has had 3 days of vomiting and diarrhoea. His blood pressure is 88 over 54, and his heart rate is 118. Blood urea nitrogen is 38, creatinine is 1.6 milligrams per decilitre, and urine sodium is eight millimoles per litre. Which of the following best describes his renin response and its main renal action? A, decreased renin release with efferent arteriolar dilation. B, increased renin release with afferent arteriolar constriction and a lower filtration fraction. C, increased renin release with efferent arteriolar constriction and a higher filtration fraction. D, increased renin release with efferent arteriolar dilation and a higher filtration fraction. E, increased renin release with efferent arteriolar constriction and a lower filtration fraction. Pause here and decide. A is out: low pressure and low sodium delivery raise renin, they do not lower it. B is out: angiotensin two constricts the efferent arteriole more than the afferent, and a lower filtration fraction would drop GFR further. D is out: dilating the efferent arteriole would lower glomerular pressure, not raise filtration. E is out: efferent constriction raises the filtration fraction, so a lower one contradicts it. So the answer is C: renin up, efferent arteriole tightened, and filtration fraction higher, which keeps GFR going.
4:54High-yield recap and next lesson
Three things to keep. One: low afferent pressure, low macula densa salt, and beta one stimulation release renin. Two: angiotensin two constricts the efferent arteriole to protect GFR, and drives aldosterone. Three: aldosterone keeps sodium and wastes potassium and hydrogen. Next up: vomiting, where this system keeps a metabolic alkalosis going.
Sources
Numbers in the text, e.g. [1], point here- Renin-angiotensin system. Wikipedia. en.wikipedia.org/wiki/Renin%E2%80%93angiotensin_system
- Renin-Angiotensin-Aldosterone System. Cardiovascular Physiology Concepts (Klabunde). cvphysiology.com/blood-pressure/bp015
- Endocrine Regulation of Kidney Function. OpenStax Anatomy and Physiology 2e. openstax.org/books/anatomy-and-physiology-2e/pages/25-5-endocrine-regulation-of-kidney-function
- Medical Pharmacology: Renal-Kidney Pharmacology and Physiology. pharmacology2000.com. pharmacology2000.com/Renal/Renal10.htm
Example lab values are illustrative.
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. All video diagrams are original (code-drawn); no third-party artwork is used in the video. Thumbnail illustration: kidney, Servier Medical Art (smart.servier.com), licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/); adapted (recoloured, outlined, resized).
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-REN-030.
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