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1. Front Back You bet! • This tutorial will take you through the RAA System (RAAS). • Here's how it's organized: • This space will give you information about the pathway, and feedback on your answers. • Main navigation buttons are to the left. • Buttons to answer questions are to the right  • And the questions you are supposed to answer appear in the bar below. Not right now Ready to start?

2. The Renin-Angiotensin-Aldosterone System is one of the most important pathways in your body. • It’s part of the vital Generalized Stress Response that you use to survive injuries and emergencies. High blood pressure High BP isn’t good for you, but it’s not an emergency. Right! That needs to be fixed pronto! That’s your rest and digest system… not an emergency. Low blood pressure Para-sympathetic system But what turns it on?

3. Good work! The Renin-Angiotensin-Aldosterone System will turn on when your blood pressure drops. • It’s often activated by the Sympathetic System, your ‘fight or flight’ response. But it can be activated by another organ too. The first word gives you a clue. liver The liver makes plasma proteins, but doesn’t turn on the RAAS. Right! The kidneys start the RAAS The spleen can release blood into the circulation, but not turn on the RAAS. kidney spleen What organ can activate the RAAS?

4. The kidneys won’t put up with low blood pressure, and they turn on the RAAS to fix it. Central baro-receptors These notice low BP and alert the SNS, not the RAAS. This is the end of the kidneys’ job. It makes more sense for them to react at thje beginning. Right! Low urine pro-duction Low renal blood flow But how did they know the BP was low?

5. That's right! decreased renal blood flow will alert the kidneys to your decrease in blood pressure. • This means that sometimes the kidneys make a mistake. If your renal arteries were blocked, for instance, the kidneys would always be turning on the RAA System, even if your blood pressure was fine. contract Decreased blood flow to kidneys They don’t have any muscle fibers. This would raise BP – but it’s from the adrenal medulla. Good work! Release epi-nephrine Release renin What will the kidneys do when they sense decreased renal blood flow?

6. This is in the pathway, but we haven’t made it yet. This is from the adrenal medulla, not made in the blood. Good work! • Right! • Renin is secreted into the blood like a hormone, but it doesn't directly influence other cells. Instead, it interacts with another protein in the blood. Angio-tensin Decreased blood flow to kidneys epi-nephrine Kidneys secrete RENIN into blood Angio-tensino-gen What protein does renin react with?

7. Angio-tensin That’s right! Angiotensin-ogenmeans ‘angiotensin maker’ – ‘gen’ as in ‘genesis’. This is from kidneys, but it’s not part of this pathway. This is actually used to make cheese… don’t mix it up with renin! Decreased blood flow to kidneys Kidneys secrete RENIN into blood Erythro-poietin RENIN reacts with angiotensinogen rennin And what will it make?

8. Look at the word again. Angio=blood vessels. Tensin=tighten Look at the word again. Angio=blood vessels. Tensin=tighten Right! • This first angiotensin is called Angiotensin I. You will see a different kind of angiotensin later. Increase heart rate Decreased blood flow to kidneys Kidneys secrete RENIN into blood RENIN reacts with angiotensinogen Increase blood volume Angiotensin I is formed Increase peripheral resistance What would something called angiotensin do to raise BP?

9. Right! This constricts vessels, but it isn’t related to angiotensin. This is the compound that created the angiotensin I! • Right! Angiotensin I constricts blood vessels in the other tissues, so there will be a higher blood pressure in the kidneys. But it isn't a very strong vasoconstrictor, so the body turns it into another compound that is stronger. Angio-tensin II Decreased blood flow to kidneys Kidneys secrete RENIN into blood RENIN reacts with angiotensinogen Epin-ephrine Angiotensin I is formed Angio-tensin-ogen What do you think it will be turned into?

10. This stands for anti-diuretic hormome Right! This stands for angiotensin converting enzyme This is atrial natriuretic factor • Right! Angiotensin II is a much stronger vasoconstrictor. It can raise the renal blood flow and make the kidneys happier. ADH Decreased blood flow to kidneys Kidneys secrete RENIN into blood RENIN reacts with angiotensinogen ACE Angiotensin I is formed A weak vasoconstrictor A strong vasoconstrictor converted to Angiotensin II ANF What enzyme turned angiotensin I angiotensin II?

11. brain A lot of your blood does go to the brain, but does all of it? Good! All the blood from the body goes through the lungs on its next circuit The kidneys get a lot of blood, but do they get all of it? • Angiotensin Converting Enzyme is so important in this pathway that some people are given drugs to block it – ACE inhibitors. Decreased blood flow to kidneys Kidneys secrete RENIN into blood RENIN reacts with angiotensinogen lungs Angiotensin I is formed A weak vasoconstrictor ACE A strong vasoconstrictor converted to Angiotensin II kidneys Where should ACE be located to process the angiotensin circulating in the blood?

12. Less blood flow Right! there still isn’t enough blood – and the kidneys are getting it! If the vessels are constricted? But there still isn’t enough blood – and the kidneys are getting it! • Since all the blood in your body has to return to the right heart and be sent through the lungs, ACE located in the lungs will be able to affect all the Angiotensin I. • Now that Angiotensin II has been produced and is constricting vessels and raising the blood pressure, the kidneys' problem might be solved. Decreased blood flow to kidneys Kidneys secrete RENIN into blood RENIN reacts with angiotensinogen More blood flow Angiotensin I is formed A weak vasoconstrictor ACE A strong vasoconstrictor converted to Angiotensin II Nothing much But what’s happening to the other organs?

13. Lower blood volume It’s already too low – that’s why BP dropped in the first place. You’ll need the kidneys to clean the blood. This is really the only way, isn’t it? • The kidneys may be happy, but the other organs may not be! This isn’t a good long-term solution. Decreased blood flow to kidneys Kidneys secrete RENIN into blood RENIN reacts with angiotensinogen Shut down kidneys Angiotensin I is formed A weak vasoconstrictor ACE A strong vasoconstrictor converted to Angiotensin II Raise blood volume What would solve the long-term problem?

14. Hypo- thalamus This controls a lot of blood composition, but is it near the kidneys? Not really a gland… Right! Adrenal means above kidneys. • To recap: There wasn’t enough blood reaching the kidneys, so they secreted RENIN to start the RAAS. • That caused angiotensin I and II to form, and those compounds constricted blood vessels, raising BP. But there still wasn’t enough blood, so now the body needs to increase blood volume. • Angiotensin II starts this process by stimulating a gland just above the kidneys. converted to Angiotensin II Cerebral cortex Adrenal cortex What gland could that be?

15. Cardiac muscle This moves the blood, but it doesn’t make more blood. Right! This makes red blood cells, but not plasma. • Right! The adrenal cortex stimulates an increase in blood volume by secreting ALDOSTERONE. • But since the adrenal cortex doesn't have the ability to make plasma, it has to tell another organ to do it. Angiotensin II Adrenal cortex releases Aldosterone Renal Na+/K+ pump Bone marrow What will the aldosterone activate to increase plasma volume?

16. 3 Na+ to blood, 2 K+ to urine Right! That would actually decrease blood volume. It’s an exchange pump, so it can’t do this. • Right! The Na+/K+ ATPase in the kidneys controls the movement of ions between the urine and the blood. Angiotensin II Adrenal cortex releases Aldosterone Renal Na+/K+ pump activated 3 Na+ to urine, 2 K+ to blood Both to blood Which way will it move these ions?

17. Into blood Right! Water follows the solutes! There are more solutes moving into the blood, so water will follow. There’s a net movement of solutes into blood, isn’t there? • The renal Na+/K+ ATPase is just like the Na+/K+ ATPase in your cells. It moves 3 Na+ from urine to blood and 2 molecules of K+ from blood to urine. • In kidney physiology, we say the Na+ is ‘reabsorbed’ and the K+ is ‘secreted.’ Angiotensin II Adrenal cortex releases Aldosterone Renal Na+/K+ pump activated Into urine 2 K+ secreted into urine 3 Na+ reabsorbed into blood No net move-ment Which way will water move?

18. Blood will become hyper-tonic This happens when blood gains solutes. This happens when blood gains water. Good! The blood gained water AND solutes, so its tonicity didn’t change. • Good work! When the 3 Na+ are reabsorbed into the blood, water will follow them. Angiotensin II Adrenal cortex releases Aldosterone Blood will become hypo-tonic Renal Na+/K+ pump activated 2 K+ secreted into urine 3 Na+ reabsorbed into blood Water follows by osmosis Blood tonicity won’t change How will this movement of water and solutes into the blood change blood osmolarity (tonicity)?

19. increase Right! You just added salt water to the blood. How will that change its volume? You just added salt water to the blood. Won’t that change its volume? • Right! As both solutes and water enter the blood, blood tonicity will not change. Angiotensin II Adrenal cortex releases Aldosterone decrease Renal Na+/K+ pump activated 2 K+ secreted into urine 3 Na+ reabsorbed into blood Water follows by osmosis No change What will happen to blood volume?

20. increase You just took salt water out of the urine. How will that change its volume? Right! You just took salt water out of the urine. Won’t that change its volume? Angiotensin II Adrenal cortex releases Aldosterone Renal Na+/K+ pump activated decrease 2 K+ secreted into urine 3 Na+ reabsorbed into blood Water follows by osmosis No change Blood volume increases What will happen to urine volume?

21. increase You moved a bunch of K+ into the urine. Will there be more or less in the blood? Right! You moved a bunch of K+ into the urine. Won’t that change blood K+? Angiotensin II Adrenal cortex releases Aldosterone Renal Na+/K+ pump activated decrease 2 K+ secreted into urine 3 Na+ reabsorbed into blood Water follows by osmosis No change Blood volume increases Urine volume decreases What will happen to blood K+ levels?

22. increase Right! You increased blood volume, didn’t you? You increased blood volume, didn’t you? Angiotensin II Adrenal cortex releases Aldosterone Renal Na+/K+ pump activated decrease 2 K+ secreted into urine 3 Na+ reabsorbed into blood Blood [K+] decreases Water follows by osmosis Urine [K+] increases No change Blood volume increases Urine volume decreases How will all this affect blood pressure?

23. Adrenal cortex releases Aldosterone They’ll need less blood They’re working hard! They need O2 to make ATP. Right! Blood volume is up, so kidneys get more! You increased blood volume, didn’t you? Renal Na+/K+ pump activated 2 K+ secreted into urine 3 Na+ reabsorbed into blood They’ll get more blood Blood [K+] decreases Water follows by osmosis Urine [K+] increases Blood volume increases Urine volume decreases No change Blood pressure increases How will all this affect the kidneys?

24. Renal Na+/K+ pump activated 3 Na+ reabsorbed into blood Water follows by osmosis Blood volume increases Urine volume decreases Blood pressure increases Renal blood flow returns to normal: kidneys stop secreting renin and the RAAS stops. Good work! You might want to try the quiz now.

25. This pathway can be found in any Anatomy and Physiology text. • cite this program as: • Bowne, P., 2015. Renin-Angiotensin-Aldosterone System Tutorial. Retrieved on [insert today's date] from the World Wide Web at [insert the URL by which you reached this tutorial]. • You can contact the author at: • pat.bowne@alverno.edu • Patricia S. Bowne • Biology Department • Alverno College • 3401 S. 39th St. • Milwaukee, WI 53234