Appendix 6: Blood Flow Kidney Podcast Transcript

Hey guys, it’s Santana and Erica again and welcome to the Kidney Unit! Welcome to the kidney unit! Here you will be introduced to the anatomy and vasculature within the kidneys as well as the overall fluid flux and hormonal regulation of the kidney. This podcast segment will focus on the key takeaways and trouble points regarding each of these sections throughout this unit.

First we will talk about the anatomy of the kidney. Understanding the general anatomy of the kidney is essential to understanding how the kidneys work as a filter for the blood and how they regulate volume within the body, which will be discussed later. You may or may not know that your body has 2 kidneys, each with the same general anatomy. If you were looking at a cross-section of a kidney, you would see an outer region, known as the cortex, and an inner region, known as the medulla. What you would not see are the thousands of tiny, microscopic structures known as nephrons, which are the functional units of the kidney. Each nephron is functionally compartmentalized, meaning it is a long tube with different parts that all work to form filtrate. Filtrate consists of the unwanted substances filtered from the blood that flow through the nephron to eventually form urine which is excreted from the body. The pathway of filtrate through each nephron starts at the Bowman’s capsule, then flows into the proximal tubule, loop of henle, distal tubule and then the collecting duct. By the time filtrate reaches the collecting duct it is essentially urine that will enter your ureter to be eliminated from the body. There are two different types of nephrons: a cortical nephron and a juxta-medullary nephron. There is one major difference between these: the cortical nephron has all of its parts primarily within the cortex, whereas a juxta-medullary nephron has a loop of henle that extends deep into the medullary space. For the rest of this unit, we mainly focus our discussions on juxta-medullary nephrons! Don’t forget to try the practice questions at the end of this unit to ensure you have a good understanding of the general anatomy of the kidney! This understanding is very important before you move on to the rest of this unit.

Now that you have an understanding of the anatomy of the kidney, and more importantly, the nephron, let’s talk about blood flow. Each nephron is closely associated with a vasculature network. If you want to see this a little bit better, you can refer to the e-textbook for a super helpful diagram showing the pathway of blood flow through each nephron. You may notice that blood flow in the kidney is different from blood flow in other tissues, such as the heart that we talked about in the previous unit. The kidney has 2 sets of arterioles: afferent and efferent arterioles. Both the afferent and efferent arteriole can relax and contract to allow for control of volume into and out of the glomerular capillary bed, which influences pressure in the glomerulus. Pressure in the glomerulus is a variable that influences filtration within the kidney. Make sure to practice drawing the flow diagrams and to help understand how vasoconstriction or vasodilation of the afferent and efferent arterioles changes pressure in the glomerulus!

The vasculature within the kidney must be tightly regulated to ensure there are not huge changes in filtration at the kidney. For example, when you’re exercising, blood pressure increases which would increase pressure in the glomerulus and increase filtration at the kidney. But, we don’t want to be changing fluid flux and losing more fluid from the body just based on relaxing or exercising. So to ensure blood flow remains constant over a wide range of mean arterial pressures, there is a mechanism known as autoregulation and the myogenic response. Many of you will be familiar with this mechanism already as it is used to regulate blood flow and vasculature in many other tissues of the body, as discussed in previous classes. Besides, we can’t forget about the equation Q equals P1 minus P2 over R quite yet! Refer to the eBook for helpful videos and diagrams to help jog your memory of this important and common concept in physiology. There is also nervous, local and endocrine control of the radius and resistance of the afferent and efferent arterioles. The key takeaway here is endocrine control, and how different hormones will dilate or constrict the arterioles to change the pressure in the glomerulus. Don’t panic yet, these hormones will be discussed in much more detail later in this podcast!

Now that you are comfortable with the anatomy and blood flow in the kidney, let’s talk about the major functions of the kidney. Keep in mind that fluid is filtered from the blood in the glomerulus into the tubule of the nephron at the Bowman’s capsule. Then, the kidney works to reabsorb the important things back into the blood and everything else is eliminated from the body as urine. The process of producing urine involves; filtration, reabsorption, secretion and excretion. Each of these processes occurs at several points along each nephron. Our discussions this class mainly focus on filtration and reabsorption. So first, let’s get into filtration. Filtration occurs at one spot along the nephron, and that’s from the blood in the glomerulus into the tubule at the bowman’s capsule. Filtration is highly dependent upon the glomerular filtration rate, or GFR. It’s extremely important that GFR remains constant despite changes in your body position or exercise rate. A big problem can occur if there is an increase in GFR resulting in increased filtration of substances into the tubule of the nephron but reduced time to reabsorb these substances back into the blood. Thus, GFR must be kept constant to prevent the loss of important solutes and fluid through excretion. GFR is regulated locally at the kidney by 3 mechanisms: the first is autoregulation and the myogenic response, hopefully, you aren’t tired of this yet! The second is tubuloglomerular feedback which is when a vasoconstrictor is released from the cells of macula densa to cause vasoconstriction of the afferent arterioles to decrease GFR. Third, there is a decreased release of the hormone renin which will decrease the local release of angiotensin II and cause vasodilation of the efferent arterioles to decrease GFR. Overall, these 3 mechanisms work to keep filtration constant and ensure there is sufficient time for reabsorption in the nephron…which we will discuss next!  Reabsorption is the movement of fluids and important solutes from the tubule back into the blood. This is extremely important as you do not want to lose things such as water, glucose, sodium or potassium in your urine. Reabsorption occurs at several places along the nephron. The vast majority of reabsorption, about 70%, occurs at the proximal tubule and the other 30% occurs in the loop on henle, late distal tubule and the collecting duct. The key takeaway here is that reabsorption in the latter half of the nephron is highly dependent upon the presence of certain hormones, which we discuss next.

The important physiological functions of the kidney are regulated by several key hormones. This is the most challenging section of this unit for most students but also the most important as these concepts are the main focus for test questions. To better help your understanding, let’s walk through each hormone and understand its major roles in the regulation of fluid flux at the kidney.  First, we have ADH. ADH is a hormone released from the posterior pituitary in the brain. Its main stimulus for release is a decrease in blood volume or mean arteriole pressure. Once released, ADH acts on the late distal tubule and collecting duct to make them permeable to water, allowing more water to be reabsorbed back into the blood. ADH also vasoconstricts the afferent arterioles greater than the efferent arterioles which will decrease GFR and increase water reabsorption. So as you can see, ADH has a pretty important role in reabsorbing water and ensuring the urine that is excreted is in small volumes that are very concentrated. Renin is a hormone that is released from the cells of the afferent and efferent arterioles in the nephrons of the kidneys. Renin is released in response to decreasing blood pressure or volume, increased SNS activity or decreased sodium chloride delivery to the macula densa. Renin converts angiotensinogen into angiotensin one which is then converted into angiotensin two. Angiotensin two is a hormone that has important roles both locally and systemically. Locally at the kidney, angiotensin two vasoconstricts the afferent arterioles to increase GFR. Systemically when angiotensin two is released in the whole body, it vasoconstricts the afferent and efferent arterioles equally to cause no change in GFR. Angiotensin two also stimulates the release of ADH and aldosterone.  Aldosterone is released from the adrenal glands and works to increase symporters in the thick ascending limb of the loop of henle. This overall causes an increase in water reabsorption. Finally, ANP is a hormone released from the heart in response to increased venous return and increased blood volume in the right atria. ANP has many opposing effects to the hormones we just talked about. Once released, it vasodilates the afferent arteriole and vasoconstricts the efferent arterioles to increase GFR and decrease water reabsorption. It also inhibits ADH and renin release resulting in decreased aldosterone release. Hopefully, this general overview of each of these 5 hormones helped your understanding of their very important roles within our body.

So, let’s go over some questions. These next 2 questions are going to focus on the integration of everything you have learned in this unit, as that depth of understanding will best help you prepare for tests! It’s also important that you understand how each hormone we have discussed in this unit can be used as a tool to help regulate the body, both locally and systemically. So for question one, let’s consider what would happen if an individual had tachycardia, meaning an increase in heart rate which would increase their mean arteriole pressure within the body. Using what you know from this unit, what would change to bring MAP back to normal Santana? Okay, a key point to remember in answering this question is that anytime there is decreased water reabsorption, there is decreased blood volume and a decrease in MAP. So, all of the hormones we know and love can be used to fix this whole-body problem. Another important relationship to note is that an increased mean arterial pressure will decrease SNS output, which will decrease renin release. Decreasing renin will inhibit the release of angiotensin two, ADH and aldosterone. In this case, decreased angiotensin two and ADH will cause systemic vasodilation to decrease MAP. A decrease in both ADH and aldosterone will also decrease water reabsorption which we know will decrease blood volume and MAP back to normal. An increase in MAP would also increase blood volume which would cause stretch of the right atria causing ANP release. We know that the release of ANP will vasodilate the afferent arterioles and vasoconstrict the efferent arterioles which will increase GFR, and decrease water reabsorption. We also know that ANP will inhibit ADH, renin and aldosterone release also causing decreased water reabsorption. So, this decrease in water reabsorption will decrease blood volume and decrease MAP! Erica and I both know that hearing these words might not put them in your brain, so go back, practice everything we just talked about and write it down and practice how everything would change if an individual had a decreased heart rate and mean arterial pressure!

Okay question two, let’s consider what happens when you lie down to go to bed and decrease your arterial pressure at the kidney and decreases GFR. How is GFR restored back to normal? First, we must identify that this problem is occurring locally at the kidney. Let’s see what local mechanisms we know of that will help to regulate GFR. The first way to increase GFR back to normal is by autoregulation and the myogenic response, which occurs in the body without conscious control. Recall that autoregulating and the myogenic response work to keep GFR constant over a range of changing mean arterial pressures. The second mechanism of regulating GFR in this situation is tubuloglomerular feedback. Locally, a decrease in GFR would decrease the delivery of sodium chloride to the macula densa in the distal tubule. In this case, a decreased delivery of sodium chloride to the macula densa would decrease the release of a vasoconstrictor from the cells of macula densa, causing vasodilation of the afferent arterioles. This vasodilation then increases GFR. Finally, a decreased delivery of sodium chloride to the macula dense is a stimulus to cause the release of renin which will increase the local release of angiotensin two and cause vasoconstriction of the efferent arterioles to increase GFR. So, from this question we now know there are 3 important mechanisms of the body to locally regulate GFR.

Amazing job everyone! We hope these two questions helped you to distinguish between local and central control and identify the tools that can be used for each situation to help regulate key functions within the body. Thanks for listening to this podcast and we hope you now have a little better understanding and appreciation for your kidneys!