13.3: Nephron — The Functional Unit of the Kidneys

The nephron is the kidney’s microscopic working unit, and is responsible for the regulation of water and soluble substances in blood.

Master this section and you'll be able to:

• Describe the major structural regions of a nephron.
• Trace the movement of filtrate and blood from the renal corpuscle through the nephron.  
• Explain what ADH is and its effect on the kidneys.

Structure of a Nephron

Within the kidneys are the microscopic functional units of the kidneys, called nephrons. Each kidney contains about one million nephrons, a number established by birth that does not increase throughout life. Each nephron filters the blood, adjusts the amounts of water and solutes that are reabsorbed or excreted, and ultimately produces urine. 

As each nephron begins to filter the blood, It allows water, electrolytes, and small solutes to enter a tubular system while keeping cells and large proteins in the bloodstream. This so called filtrate flows  through the nephron’s winding tubules, the kidneys have ample opportunity to fine-tune its composition by reabsorbing substances the body needs, such as water, glucose, and amino acids, and by secreting additional wastes or excess ions that must be eliminated.

Each nephron has two major regions: the renal corpuscle and the renal tubule:

1. The renal corpuscle includes the glomerulus, a capillary bed where filtration begins, and the Bowman’s capsule, which collects the filtered fluid.
    
2. The renal tubules make up the remainder of the nephron and include three main segments: the proximal convoluted tubule, the loop of Henle (with descending and ascending limbs), and the distal convoluted tubule. These winding tubules allow the kidneys to adjust the filtrate by reabsorbing needed substances and secreting additional wastes.

Overall, the nephron’s job is to filter the blood, reclaim essential water and solutes, and form urine from what the body does not need. Nephron activity helps regulate blood volume, blood pressure, and plasma osmolarity, and is influenced by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone.

Figure \(\PageIndex{1}\): Structure of a Nephron. Shown is the structure of a Juxtamedullary Nephron (left) and a Cortical Nephron (right). Nephrons are the functional units of the kidney. Filtration begins in the renal corpuscle, where blood is filtered into the start of the renal tubule. The filtrate then moves through the proximal convoluted tubule, descends and ascends through the loop of Henle, and continues into the distal convoluted tubule. These segments adjust the amounts of water and solutes that are reabsorbed or secreted. Multiple nephrons empty their final filtrate into a collecting duct, which carries forming urine toward the renal pelvis.

The Glomerulus

The glomerulus is a tuft of fenestrated capillaries, which means the capillary walls contain tiny pores that allow water and many small solutes to pass through quickly. Fenestrated capillaries are found in places where rapid filtration or exchange is essential, such as the kidneys, intestines, and endocrine glands.

Unlike other capillary beds, glomerular capillaries begin at an afferent arteriole and drain into an efferent arteriole, rather than into a venule. Because the efferent arteriole is narrower, pressure inside the glomerulus stays high. The body can adjust this pressure by changing the diameter of the afferent and efferent arterioles. The fluid and solutes filtered out of the glomerulus collect in Bowman’s capsule, beginning their journey through the nephron.

The Bowman’s capsule — also called the glomerular capsule — surrounds the glomerulus. It is composed of visceral (simple squamous epithelial cells; inner) and parietal (simple squamous epithelial cells; outer) layers. The visceral layer lies just beneath the thickened glomerular basement membrane and only allows fluid and small molecules like glucose and ions like sodium to pass through into the nephron.

Red blood cells and large proteins, such as serum albumins, cannot pass through the glomerulus under normal circumstances. However, in some injuries they may be able to pass through and can cause blood and protein content to enter the urine, which is a sign of problems in the kidney.

Proximal Convoluted Tubule (PCT)

The proximal convoluted tubule (PCT) is a significant component of the nephron. Starting at the Bowman's capsule in the renal cortex, the PCT plays a vital role in reabsorbing essential substances and regulating urine composition. It is a convoluted tube with a simple cuboidal epithelium lined by a brush border of microvilli on its luminal (apical) surface. The microvilli dramatically increases the surface area for absorption.

The PCT is the first site of water reabsorption into the bloodstream, and the site where the majority of water and salt reabsorption takes place. Water reabsorption in the proximal convoluted tubule occurs due to both passive diffusion and active transport from Na⁺/K⁺/ATPase pumps that actively transports sodium back into the blood.

Water and glucose follow sodium in a process called co-transport. Approximately 65% of water and — under normal conditions — 100% of the glucose in the nephron are reabsorbed by cotransport in the PCT. Various other essential solutes like amino acids, vitamins, and ions (e.g., sodium, potassium, calcium, and bicarbonate) are also reabsorbed in the PCT. Unfortunately, the PCT is highly susceptible to damage from various toxins and medications, which can disrupt its reabsorptive functions, a consideration in clinical settings where drug-induced kidney damage may occur.​

The PCT also participates in the secretion of specific organic molecules and waste products, such as drugs and hydrogen ions. The reabsorption of bicarbonate ions and the secretion of hydrogen ions help regulate the pH of the blood and, consequently, the body's overall acid-base balance. 

Filtrate leaving this tubule generally is unchanged due to the equivalent water and ion reabsorption, with an osmolarity (ion concentration) of 300 mOSm/L, which is the same osmolarity as normal plasma.

Nephron Loop or Loop of Henle 

The Loop of Henle is a U-shaped section of the nephron that carries filtrate from the PCT to the distal convoluted tubule (DCT). It is divided into two segments: the descending and ascending limbs.  Its two limbs have opposite jobs that help concentrate and then dilute the filtrate.

• The descending limb lets water leave but does not let ions leave. Because the medulla around it is very salty, water moves out of the LOH, making the filtrate more concentrated as it travels downward.
• The ascending limb does the opposite. It lets ions leave (especially sodium and chloride) but does not let water leave. As ions are pumped out, the filtrate becomes more dilute as it heads toward the distal tubule.

Distal Convoluted Tubule (DCT) and Collecting Duct (CD)

The distal convoluted tubule (DCT) and the collecting duct are the last places where the nephron can adjust what stays in the body and what becomes urine. Their permeability to water and ions is not fixed. Instead, their permeability changes depending on hormones, allowing the kidneys to help control blood osmolarity, volume, blood pressure, and pH.

The DCT also secretes substances into the filtrate, including potassium ions and certain drugs or toxins.

Multiple DCTs drain into a shared collecting duct, which is not considered part of any one nephron but is continuous with them. Each collecting duct receives filtrate from many nephrons and carries it downward through the cortex and into the medulla for final adjustments. As these ducts descend, they merge to form larger terminal ducts that open at the renal papilla.

The collecting duct (CD) functions much like the DCT, especially in its response to the antidiuretic hormone. When ADH is present, the walls of the collecting duct become more permeable to water, allowing additional water to be reabsorbed into the bloodstream. By the time the fluid finishes its passage through the collecting duct and enters the renal pelvis on its way to the ureter, all processing is complete and the filtrate is now considered urine.

Anti-Diuretic Hormone Feedback

One of the hormones that acts on the distal convoluted tubule (DCT) and especially the collecting duct is ADH (antidiuretic hormone). Antidiuretic means “against making urine.” An antidiuretic substance reduces the amount of urine the body produces. The main antidiuretic in the human body is the antidiuretic hormone. When your body needs to save water, ADH tells the kidneys to reabsorb more water and release less of it as urine. As a result, urine volume goes down and the body conserves water.

ADH is released from the posterior pituitary gland when plasma osmolarity increases, meaning the blood has become too concentrated. This usually happens when plasma volume drops or when ion concentration rises relative to the amount of water in the blood.

Osmoreceptors in the hypothalamus detect this increase in osmolarity and signal the posterior pituitary to release ADH. Once released, ADH travels to the kidneys and acts on the nephrons to retain water, lower plasma osmolarity, and produce urine that is more concentrated.

ADH works by increasing the water permeability of the DCT and the collecting duct, which are normally impermeable to water. With ADH present, more water is reabsorbed back into the bloodstream. This reabsorption increases blood volume and reduces the volume of urine produced.

When plasma volume goes up and therefore osmolarity returns to normal, the hypothalamic osmoreceptors stop sending signals, ADH release decreases, and the system returns to baseline. This makes ADH regulation a clear example of negative feedback.

 

Many substances that we ingest can act as diuretics or antidiuretics, albeit with different mechanisms.

A common example is alcohol and water ingestion, which directly inhibit ADH secretion in the pituitary gland.

Alternatively caffeine is a diuretic because it interferes with sodium reabsorption (reducing the amount of water reabsorbed by sodium cotransport) and increases the glomerular filtration rate by temporarily increasing blood pressure. Also, many medications act as diuretics because they slow water reabsorption.

Peritubular Capillaries

After blood leaves the glomerulus through the efferent arteriole, it does not return directly to the veins. Instead, it enters a second capillary network called the peritubular capillaries, which wrap closely around the proximal and distal convoluted tubules. These capillaries are low-pressure vessels that allow easy movement of water, ions, glucose, and other useful solutes back into the bloodstream. They also provide a route for the secretion of additional wastes from the blood into the nephron. In this way, the peritubular capillaries work hand-in-hand with the nephron tubules to fine-tune the composition of the filtrate and maintain homeostasis.

Figure \(\PageIndex{2}\): The Nephron and Its Associated Blood Vessels. Filtrate moves through the nephron while interacting closely with the kidney’s blood supply. Filtration starts in the glomerulus within the glomerular capsule, where water and small solutes enter the nephron. The filtrate then flows through the PCT for major reabsorption, continues through the descending and ascending limbs of the nephron loop , and reaches the DCT for further ion regulation. It then enters the collecting duct, where water reabsorption is hormonally controlled. The peritubular capillary network, return reabsorbed substances to the bloodstream.  

Do the Kidneys Have a Portal System?

You have previously learned that a portal system is a special circulatory pathway in which blood flows through two consecutive capillary beds before returning to the heart. Instead of going straight from one capillary bed back to the venous system, the blood is routed into a second capillary network. This arrangement allows substances picked up or released in the first capillary bed to be modified, filtered, or adjusted in the second. You learned about the hypophyseal portal system and the hepatic portal system in previous modules.

The kidneys do indeed have two capillary beds in a row, but they are not considered a portal system. A true portal system requires a vein connecting one capillary bed to the next. In the kidneys, the first capillary bed (the glomerulus) drains into an efferent arteriole, which then leads to the second capillary bed (the peritubular capillaries). Because an arteriole, not a vein, connects the two, the kidneys do not meet the definition of a portal system.

Nevertheless, the kidney’s design is still unusual and highly specialized. The two capillary beds in the kidneys are the

1. Glomerular capillaries, located inside the renal corpuscle. These capillaries are uniquely specialized for filtration. They are high-pressure, fenestrated capillaries that push plasma out of the blood to form the initial filtrate.
    
2. Peritubular capillaries, surrounding parts of the nephron, they are designed for reabsorption and secretion. Their job is to reclaim water, ions, glucose, and other useful materials from the filtrate and return them to the blood. 

In Summary

A portal system requires: capillary bed → vein → second capillary bed.

But in the kidneys, the connection is: capillary bed → arteriole → second capillary bed.

Therefore, the kidneys do not have a portal system. Their very specialized vessel set-up, however, matters greatly, because arterioles can change diameter and therefore regulate pressure entering the second capillary bed. This regulation is essential for kidney function.