Urine Production in Kidneys

The kidneys of the urinary system are primarily responsible for water and electrolyte (electrically charged chemical) regulation in the body. A nephron is the primary structure in the kidney that produces urine, by filtering blood and modifying the filtrate (portion of blood that enters the nephron). This process removes waste products and excess solutes (dissolved substances) from the body, keeping the body fluids at homeostasis. Each human kidney contains around a million nephrons. Nephrons consist of long, looped tubes that begin and end in the renal cortex (outer layer of the kidney) but that dip down into the renal medulla (the inner region of the kidney that looks like pyramids in the frontal section). At one end of the tube is a closed, cuplike structure where blood filtration occurs, called the glomerular capsule (Bowman's capsule). This capsule surrounds a capillary bed, called the glomerulus, where blood filtration takes place. Together these structures make up the renal corpuscle. The glomerular capsule leads to the renal tubules.

The glomerulus and glomerular capsule of the nephron filter blood, and the filtrate flows into the nephron. As the filtrate moves through the renal tubules, it is modified through the secretion and reabsorption of different substances. Secretion is the process of moving solutes that hadn't been filtered from the blood during the filtration process into the tubule fluid. Reabsorption is the process of removing tubular fluid back into the blood. The final product of the nephron then moves to the collecting duct, where the modified filtrate is ultimately converted to urine.

During filtration a portion of blood passing through the glomerulus is forced out of the capillary bed and into the glomerular capsule. The substances that cross are primarily dependent on size. Proteins and cells are too large to pass, but smaller dissolved solutes enter the nephron. This initial filtrate is similar to the composition of plasma (the fluid portion of blood) without the blood proteins. Since this process is not very selective, the filtrate needs to be further modified to keep important solutes, such as glucose and amino acids, through reabsorption and to eliminate extra substances, such as toxins and excess electrolytes, via secretion.

The proximal convoluted tubule (PCT) is the segment of the nephron that receives the initial filtrate from the glomerular capsule and modifies the filtrate through the process of reabsorption and secretion. The PCT is responsible for reabsorbing about 85 percent of the contents of the filtrate. The walls of the PCT consist of epithelial cells (thin sheets of cells) covered in microvilli called brush border cells. These microvilli are fingerlike projections that greatly increase the surface area of the PCT. This increases the rate of reabsorption of nutrients and water from the filtrate back into the interstitial fluid and from there into the surrounding capillaries and back into the blood. After traveling through the PCT, the tubular fluid is primarily a mixture of water, salt, and urea (a toxic nitrogen-containing molecule generated from the breakdown of proteins during normal metabolism).

After the PCT the tubular fluid reaches the next part of the nephron, the nephron loop (loop of Henle), a section of the nephron that dips down into the renal medulla and functions to create a concentration gradient in the renal medulla. A concentration gradient is a gradual difference in the concentration of particles between two different regions, in this case between the top regions of the loop and the bottom region deep in the renal medulla. The first part of the loop, the descending limb, is permeable to water but not to salts or urea. The second part of the loop, the ascending limb, has a thin and a thick portion. The thin ascending limb is impermeable to water but permeable to salts. The thick ascending limb is also impermeable to water, and it actively transports salts out of the tubular fluid. The countercurrent flow (flow in opposite directions) between the parallel and adjacent descending and ascending limbs and the difference in how each limb handles water and sodium ions set up the concentration gradient. As the filtrate moves down the descending limb, the fluid becomes more concentrated as water leaves the tubule. While traveling up the ascending limb, sodium is actively being pumped out, making the fluid more dilute. The filtrate is at its most dilute when leaving the ascending limb of the nephron loop.

After traveling through the nephron loop, the tubular fluid reaches the distal convoluted tubule (DCT), the final segment of the nephron, where ion concentrations are further modified through secretion and reabsorption. This additional secretion and reabsorption takes place to refine blood pH, sodium and potassium levels, and calcium levels. The DCT ends in the connecting tubule, which leads to the collecting duct. The collecting duct is a duct in the kidney that collects the fluid produced by the nephron. This structure determines the final concentration of the urine based on hormonal input.

There are two types of nephrons, cortical nephrons and juxtamedullary nephrons. The renal corpuscle of a cortical nephron is found in the outer region of the renal cortex, and the nephron loop does not descend very far into the renal medulla. The renal corpuscle of a juxtamedullary nephron is located in the inner region of the renal cortex, and the nephron loop descends deep into the renal medulla. The juxtamedullary nephrons only make up about 15 percent of the nephrons but play an essential role in the ability of the kidney to concentrate urine.

Although the nephrons are responsible for producing urine, the role of the blood vessels associated with the nephron is equally important. Afferent arterioles carry unfiltered blood to the glomerulus, and efferent arterioles carry the newly filtered blood out of the glomerulus. These arterioles help regulate the rate of filtration, where a portion of the plasma (fluid noncellular portion of blood) and small, soluble blood components including waste products and nutrients leave the blood and enter the glomerular capsule. Nonfilterable blood components, such as platelets (cell fragments used for blood clotting), large proteins, and blood cells, are left behind in the efferent arteriole.

The efferent arterioles lead to the peritubular capillaries, the capillaries that are interwoven around the tubules of the nephrons. The blood in these capillaries picks up materials reabsorbed from the nephrons. Some solutes, such as potassium, acids, bases, drugs, and toxins, that are still in the blood when it reaches the peritubular capillaries are secreted into the nephron tubules. In juxtamedullary nephrons the peritubular capillaries that run parallel to the long nephron loops are ladder-shaped and referred to as vasa recta. These vessels are permeable to water and solutes, which allows for the maintenance of the concentration gradient set up by the nephron loop. As the vasa recta vessels descend into the renal medulla, the osmotic concentration of the blood is allowed to increase along with the other extracellular fluids.

Urine production occurs in three processes: blood filtration, tubular reabsorption, and tubular secretion. The passive process involving the transfer of water and soluble components, such as nutrients, electrolytes (electrically charged chemicals), and waste from the blood into the glomerular capsule of the nephron is called blood filtration. The glomerular capillaries are fenestrated, meaning they have perforations in their walls. The types of materials filtered out of the blood are based on their size. Salts, sugars, amino acids, and hydrogen ions are small enough to pass through the openings in the filtration membranes, whereas blood cells, platelets, and proteins are too large. Therefore, cells and proteins are not present in the filtrate. The filtrate produced has a similar composition to blood plasma (the fluid noncellular portion of blood) but does not contain proteins, as they are too large to pass through the capillaries.

Afferent and efferent arterioles can regulate the hydrostatic pressure within the glomerulus, which can change the glomerular filtration rate, or how quickly the blood is filtered. Hydrostatic pressure is the pressure exerted on the walls of the arterioles from the physical force of blood being pumped through the vessels. The higher the hydrostatic pressure, the more fluid is pushed through the walls of the glomerulus capillary and the glomerular capsule of the nephron. Hydrostatic pressure in the glomerulus is the main driving force determining the filtration rate. This pressure is counteracted by the osmotic pressure of the blood from the proteins that cannot leave, thus drawing water back into the glomerulus, and by the hydrostatic pressure of the glomerular capsule. The afferent and efferent arterioles contain sphincters that can be adjusted to change the blood pressure within the glomerulus, changing the filtration rate. If blood pressure is too high in the glomerulus, the walls could be damaged. The afferent arteriole walls will constrict when overall blood pressure rises to prevent this from happening. Filtration rate may need to be lowered if blood moves too quickly through the glomerulus, not allowing enough time to filter out the materials. The juxtamedullary complex is the point of contact between the end of the ascending limb of the nephron loop and the afferent arteriole. This complex allows self-regulation of the glomerular filtration rate in the renal corpuscle. The sodium concentration of the tubular fluid in the nephron loop provides feedback to the arterioles about whether there is enough time for sodium reabsorption to occur. If sodium levels are too high, the glomerular filtration rate decreases until the sodium concentration in the tubular fluid entering the distal convoluted tubule decreases.

The filtrate is modified as it moves through the nephron by reabsorption and secretion. Substances the body should keep are reabsorbed back into the bloodstream, and additional substances still left in the peritubular capillaries are secreted into the filtrate. The nephron loop sets up a concentration gradient, so when the modified filtrate travels down the collecting tubule, water can be reabsorbed to produce a highly concentrated urine.

Most of the water and dissolved substances that are filtered out of the blood are reabsorbed by the nephron tubules. Reabsorption is the transport of materials from the nephron back into the bloodstream. Depending on the substance being reabsorbed, this process can be active or passive. Some substances move through the nephron cells (transcellular), and other substances move between the cells (paracellular). Important molecules such as sugars and amino acids are completely reabsorbed into the bloodstream while electrolyte reabsorption depends on the levels in the blood. Substances reabsorbed in the PCT include water, electrolytes (sodium, potassium, chloride, magnesium, calcium, etc.), glucose, amino acids, vitamins, and urea. The nephron loop reabsorbs water and electrolytes (primarily sodium, chloride, and potassium) and does so in a way that allows an osmotic concentration gradient to form. The reabsorption of substances in the DCT is tightly regulated by hormones in order to make final adjustments to the tubular fluid prior to reaching the collecting duct. Sodium, chloride, and calcium are reabsorbed in the DCT.

Because sodium is the most predominant positively charged electrolyte in extracellular fluid, it is also the most abundant in the filtrate. Transport of sodium ions out of the tubule is transcellular and allows reabsorption of other solutes and water. Sodium is actively transported through the basal surface (side facing the outside of the tubule) of the tubule cell and into the interstitial space using Na+/K+ ATPase pumps. On the apical surface (the inside of the tubule), sodium ions are transported using facilitated diffusion (passive transport using a protein carrier) or using secondary active transport, where sodium ions move down their concentration gradient as another solute such as glucose, amino acids, vitamins, or other electrolytes is actively transported. These cotransported solutes leave the basal side by facilitated diffusion. Water passively follows the solutes through aquaporins, water channels embedded in the cell membranes.

Secretion is the transport of a substance from the blood into the nephrons. These are substances such as waste products, some drugs, minerals, potassium, and hydrogen ions. Some of these are secreted because of their toxicity and others to help regulate the normal blood levels. Nitrogenous waste products from protein metabolism are toxic to cells and therefore are secreted into the tubular fluid. Urea is the most abundant and least toxic of these nitrogenous waste products, but other forms, such as ammonia and uric acid, are also secreted. Secretion of minerals, potassium, and hydrogen ions is dependent on the internal composition of these solutes. When in excess, secretion on the solute is upregulated. The mechanism of secretion is the same as in reabsorption except in the opposite direction.