Renal Blood Flow and its Regulation

Learning Objectives

By the end of this section, you will be able to:

  • Describe the nerve supply to the kidney.
  • Describe how the nervous system, hormones, and the kidney regulate glomerular filtration.
  • Describe how the nephron regulates water excretion.

Vasculature of the kidney

The renal artery provides the blood flow to the kidney.  The renal artery first divides into segmental arteries, followed by further branching to form multiple interlobar arteries that pass through the renal columns to reach the cortex. The interlobar arteries, in turn, branch into arcuate arteries, cortical radiate arteries, and then into afferent arterioles. The afferent arterioles service about 1.3 million nephrons in each kidney.

This figure shows the network of blood vessels and the blood flow in the kidneys.

Figure 4. Blood Flow in the Kidney

 

It is vital that the flow of blood through the kidney be at a suitable rate to allow for filtration. This rate determines how much solute is retained or discarded, how much water is retained or discarded, and ultimately, the osmolarity of blood and the blood pressure of the body.

Vascular surrounding individual nephrons

Nephrons are the “functional units” of the kidney. Because nephrons function is to cleanse the blood and balance the constituents of the circulation, they obviously require a close connection to the blood supply. The filtration apparatus of the nephron, Bowman’s capsule, removes a large volume of filtrate from the blood. It does this by surrounding a high pressure fenestrated capillary bed that is about 200 µm in diameter called the glomerulus. The glomerulus has unusually high pressure relative to other capillary beds. It is the only capillary bed that has both an efferent arteriole (instead of the expected efferent venule). This high pressure helps drive the continued movement of fluid from the blood, across the filtration membrane, and into Bowman’s capsule. The glomerulus and Bowman’s capsule together form the renal corpuscle.

After passing through the renal corpuscle, the capillaries form a second arteriole, the efferent arteriole. These efferent arterioles will feed the next capillary networks around the more distal portions of the nephron tubule, the peritubular capillaries and vasa recta, before returning to the venous system. Peritubular capillaries and vasa recta have a more standard anatomical arrangement, with afferent arterioles and efferent venules. Because of this, they also have a more typical blood pressure, which is substantially lower than the pressure in glomeruli.

As the filtrate moves through the nephron tubules, these capillary networks recover most of the solutes and water, and return them to the circulation. Since a capillary bed (the glomerulus) drains into a vessel that in turn forms a second capillary bed, the definition of a portal system is met. This is the only portal system in which an arteriole is found between the first and second capillary beds. (Portal systems also link the hypothalamus to the anterior pituitary, and the blood vessels of the digestive viscera to the liver.)

This image shows the blood vessels and the direction of blood flow in the nephron.

Figure 3. The two capillary beds are clearly shown in this figure. The efferent arteriole is the connecting vessel between the glomerulus and the peritubular capillaries and vasa recta.

 Visit this link to view an interactive tutorial of the flow of blood through the kidney.

Regulation of filtrate formation

The rate of filtration is directly correlated to the amount of filtrate being produced by the renal corpuscle at any time. To increase filtration, the blood flow to the glomerulus must be increased, as this will permit additional filtrate to be produced. To reduce the filtration rate, the blood flow to the glomerulus is reduced, as this will consequently reduce the pressure in the glomerulus, thereby limiting filtrate formation. The blood flow to the glomerulus is regulated  by several mechanisms.

Sympathetic Nerves

The kidneys are innervated by the sympathetic neurons of the autonomic nervous system via the celiac plexus and splanchnic nerves. Reduction of sympathetic stimulation results in vasodilation and increased blood flow through the kidneys during resting conditions. Therefore, a reduction in sympathetic stimulation results in increased urine production. Conversely, an increase in sympathetic stimulation would reduce filtrate formation, and ultimately, urine production.

When the frequency of sympathetic stimulation increases, the arteriolar smooth muscle constricts (vasoconstriction), resulting in diminished glomerular flow, so less filtration occurs. Under conditions of stress, sympathetic nervous activity increases, resulting in the direct vasoconstriction of afferent arterioles (norepinephrine effect) as well as stimulation of the adrenal medulla. The adrenal medulla, in turn, produces a generalized vasoconstriction through the release of epinephrine. This includes vasoconstriction of the afferent arterioles, further reducing the volume of blood flowing through the kidneys. This process redirects blood to other organs with more immediate needs.

If blood pressure falls, the sympathetic nerves will also stimulate the release of renin. Additional renin increases production of the powerful vasoconstrictor angiotensin II. Angiotensin II, as discussed above, will also stimulate aldosterone production to augment blood volume through retention of more Na+ and water. Only a 10 mm Hg pressure differential across the glomerulus is required for a normal glomerular filtration rate, so very small changes in afferent arterial pressure significantly increase or decrease glomerular filtration rate.

Autoregulation of blood flow to kidneys

The kidneys are very effective at regulating the rate of blood flow over a wide range of blood pressures. Your blood pressure will decrease when you are relaxed or sleeping. It will increase when exercising. Yet, despite these changes, the filtration rate through the kidney will change very little. This is due to two internal autoregulatory mechanisms that operate without outside influence: the myogenic mechanism and the tubuloglomerular feedback mechanism.

Arteriole Myogenic Mechanism

The myogenic mechanism regulating blood flow within the kidney depends upon a characteristic shared by most smooth muscle cells of the body. When you stretch a smooth muscle cell, it contracts; when you stop, it relaxes, restoring its resting length. This mechanism works in the afferent arteriole that supplies the glomerulus. When blood pressure increases, smooth muscle cells in the wall of the arteriole are stretched and respond by contracting to resist the pressure, resulting in little change in flow. When blood pressure drops, the same smooth muscle cells relax to lower resistance, allowing a continued even flow of blood.

Tubuloglomerular Feedback

The tubuloglomerular feedback mechanism involves the juxtaglomerular apparatus (Figure 3) and a paracrine signaling mechanism utilizing adenosine triphosphate (ATP), adenosine, and nitric oxide (NO). This mechanism stimulates either contraction or relaxation of afferent arteriolar smooth muscle cells. Recall that the distal convoluted tubule is in intimate contact with the afferent and efferent arterioles of the glomerulus. Specialized macula densa cells in this segment of the tubule respond to changes in the fluid flow rate and Na+ concentration. As the glomerular filtratation rate increases, there is less time for NaCl to be reabsorbed in the proximal convoluted tubule, resulting in higher osmolarity in the filtrate. The increased fluid movement more strongly deflects single nonmotile cilia on macula densa cells. This increased osmolarity of the forming urine, and the greater flow rate within the distal convoluted tubule, activates macula densa cells to respond by releasing ATP and adenosine (a metabolite of ATP). ATP and adenosine act locally as paracrine factors to stimulate the myogenic juxtaglomerular cells of the afferent arteriole to constrict, slowing blood flow and reducing the glomerular filtratation rate. Conversely, when the glomerular filtratation rate decreases, less Na+ is in the forming urine, and most will be reabsorbed before reaching the macula densa, which will result in decreased ATP and adenosine, allowing the afferent arteriole to dilate and increase the glomerular filtratation rate. Nitric oxide has the opposite effect, relaxing the afferent arteriole at the same time ATP and adenosine are stimulating it to contract. Thus, nitric oxide fine-tunes the effects of adenosine and ATP on the glomerular filtratation rate.

Table 1. Paracrine Mechanisms Controlling Glomerular Filtration Rate
Change in GFR NaCl Absorption Role of ATP and adenosine/Role of NO Effect on GFR
Increased GFR Tubular NaCl increases ATP and adenosine increase, causing vasoconstriction Vasoconstriction slows GFR
Decreased GFR Tubular NaCl decreases ATP and adenosine decrease, causing vasodilation Vasodilation increases GFR
Increased GFR Tubular NaCl increases NO increases, causing vasodilation Vasodilation increases GFR
Decreased GFR Tubular NaCl decreases NO decreases, causing vasoconstricton Vasoconstriction decreases GFR

Lying just outside Bowman’s capsule and the glomerulus is the juxtaglomerular apparatus (Figure 3). At the juncture where the afferent and efferent arterioles enter and leave Bowman’s capsule, the initial part of the distal convoluted tubule comes into direct contact with the arterioles. The wall of the distal convoluted tubule at that point forms a part of the JGA known as the macula densa. This cluster of cuboidal epithelial cells monitors the fluid composition of fluid flowing through the distal convoluted tubule. In response to the concentration of Na+ in the fluid flowing past them, these cells release paracrine signals. They also have a single, nonmotile cilium that responds to the rate of fluid movement in the tubule. The paracrine signals released in response to changes in flow rate and Na+ concentration are ATP and adenosine.

The top panel of this image shows the cross section of the juxtaglomerular apparatus. The major parts are labeled.

Figure 3. (a) The juxtaglomerular apparatus allows specialized cells to monitor the composition of the fluid in the distal convoluted tubule and adjust the glomerular filtration rate. (b) This micrograph shows the glomerulus and surrounding structures. LM × 1540. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

A second cell type in this apparatus is the juxtaglomerular cell. This is a modified, smooth muscle cell lining the afferent arteriole that can contract or relax in response to ATP or adenosine released by the macula densa. Such contraction and relaxation regulate blood flow to the glomerulus. If the osmolarity of the filtrate is too high (hyperosmotic), the juxtaglomerular cells will contract, decreasing the glomerular filtration rate (GFR) so less plasma is filtered, leading to less urine formation and greater retention of fluid. This will ultimately decrease blood osmolarity toward the physiologic norm. If the osmolarity of the filtrate is too low, the juxtaglomerular cells will relax, increasing the glomerular filtration rate and enhancing the loss of water to the urine, causing blood osmolarity to rise. In other words, when osmolarity goes up, filtration and urine formation decrease and water is retained. When osmolarity goes down, filtration and urine formation increase and water is lost by way of the urine. The net result of these opposing actions is to keep the rate of filtration relatively constant. A second function of the macula densa cells is to regulate renin release from the juxtaglomerular cells of the afferent arteriole (Figure 4). Active renin is a protein comprised of 304 amino acids that cleaves several amino acids from angiotensinogen to produce angiotensin I. Angiotensin I is not biologically active until converted to angiotensin II by angiotensin-converting enzyme (ACE) from the lungs. Angiotensin II is a systemic vasoconstrictor that helps to regulate blood pressure by increasing it. Angiotensin II also stimulates the release of the steroid hormone aldosterone from the adrenal cortex. Aldosterone stimulates Na+ reabsorption by the kidney, which also results in water retention and increased blood pressure.

This diagram shows the pathway of action of the renin-aldosterone-angiotensin system. An arrow in the center of the image shows the sequence of events that take place, and branching off from this arrow are indications of where in the body these events take place.

Figure 4. The enzyme renin converts the pro-enzyme angiotensin I; the lung-derived enzyme ACE converts angiotensin I into active angiotensin II.

Chapter Review

The kidneys are innervated by sympathetic nerves of the autonomic nervous system. Sympathetic nervous activity decreases blood flow to the kidney, making more blood available to other areas of the body during times of stress. The arteriolar myogenic mechanism maintains a steady blood flow by causing arteriolar smooth muscle to contract when blood pressure increases and causing it to relax when blood pressure decreases. Tubuloglomerular feedback involves paracrine signaling at the juxtaglomerular apparatus to cause vasoconstriction or vasodilation to maintain a steady rate of blood flow.Contractile mesangial cells further perform a role in regulating the rate at which the blood is filtered. Specialized cells in the juxtaglomerular apparatus produce paracrine signals to regulate blood flow and filtration rates of the glomerulus. Other juxtaglomerular apparatus cells produce the enzyme renin, which plays a central role in blood pressure regulation

Self Check

Answer the question(s) below to see how well you understand the topics covered in the previous section.

Critical Thinking Questions

  1. Explain what happens to Na+ concentration in the nephron when GFR increases.
  2. If you want the kidney to excrete more Na+ in the urine, what do you want the blood flow to do?

Glossary

myogenic mechanism: mechanism by which smooth muscle responds to stretch by contracting; an increase in blood pressure causes vasoconstriction and a decrease in blood pressure causes vasodilation so that blood flow downstream remains steady

tubuloglomerular feedback: feedback mechanism involving the JGA; macula densa cells monitor Na+ concentration in the terminal portion of the ascending loop of Henle and act to cause vasoconstriction or vasodilation of afferent and efferent arterioles to alter GFR