Substances that are nonfilterable in the glomerulus exit the nephron through the afferent arteriole.

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Urine is formed in three steps: filtration, reabsorption, and secretion.

Learning Objectives

• Summarize the steps in urine formation

Key Points

• Filtration involves the transfer of soluble components, such as water and waste, from the blood into the glomerulus.
• Reabsorption involves the absorption of molecules, ions, and water that are necessary for the body to maintain homeostasis from the glomerular filtrate back into the blood.
• Secretion involves the transfer of hydrogen ions, creatinine, drugs, and urea from the blood into the collecting duct, and is primarily made of water.
• Blood and glucose are not normally found in urine.

• urine: A liquid excrement consisting of water, salts, and urea, which is made in the kidneys then released through the urethra.
• glomerulus: A small, intertwined group of capillaries within nephrons of the kidney that filter the blood to make urine.

Urine is a waste byproduct formed from excess water and metabolic waste molecules during the process of renal system filtration. The primary function of the renal system is to regulate blood volume and plasma osmolarity, and waste removal via urine is essentially a convenient way that the body performs many functions using one process.
Urine formation occurs during three processes:

1. Filtration
2. Reabsorption
3. Secretion

During filtration, blood enters the afferent arteriole and flows into the glomerulus where filterable blood components, such as water and nitrogenous waste, will move towards the inside of the glomerulus, and nonfilterable components, such as cells and serum albumins, will exit via the efferent arteriole. These filterable components accumulate in the glomerulus to form the glomerular filtrate.

Normally, about 20% of the total blood pumped by the heart each minute will enter the kidneys to undergo filtration; this is called the filtration fraction. The remaining 80% of the blood flows through the rest of the body to facilitate tissue perfusion and gas exchange.

The next step is reabsorption, during which molecules and ions will be reabsorbed into the circulatory system. The fluid passes through the components of the nephron (the proximal/distal convoluted tubules, loop of Henle, the collecting duct) as water and ions are removed as the fluid osmolarity (ion concentration) changes. In the collecting duct, secretion will occur before the fluid leaves the ureter in the form of urine.

During secretion some substances±such as hydrogen ions, creatinine, and drugs—will be removed from the blood through the peritubular capillary network into the collecting duct. The end product of all these processes is urine, which is essentially a collection of substances that has not been reabsorbed during glomerular filtration or tubular reabsorbtion.

Urine is mainly composed of water that has not been reabsorbed, which is the way in which the body lowers blood volume, by increasing the amount of water that becomes urine instead of becoming reabsorbed. The other main component of urine is urea, a highly soluble molecule composed of ammonia and carbon dioxide, and provides a way for nitrogen (found in ammonia) to be removed from the body. Urine also contains many salts and other waste components. Red blood cells and sugar are not normally found in urine but may indicate glomerulus injury and diabetes mellitus respectively.

Normal kidney physiology: This illustration demonstrates the normal kidney physiology, showing where some types of diuretics act, and what they do.

Nephrons: The Functional Unit

Nephrons take a simple filtrate of the blood and modify it into urine. Many changes take place in the different parts of the nephron before urine is created for disposal. The term forming urine will be used hereafter to describe the filtrate as it is modified into true urine. The principle task of the nephron population is to balance the plasma to homeostatic set points and excrete potential toxins in the urine. They do this by accomplishing three principle functions—filtration, reabsorption, and secretion. They also have additional secondary functions that exert control in three areas: blood pressure (via production of renin), red blood cell production (via the hormone EPO), and calcium absorption (via conversion of calcidiol into calcitriol, the active form of vitamin D).

Urine is a waste byproduct formed from excess water and metabolic waste molecules during the process of renal system filtration. The primary function of the renal system is to regulate blood volume and plasma osmolarity, and waste removal via urine is essentially a convenient way that the body performs many functions using one process.

Steps involved in urine formation are  Glomerular filtration,  Tubular reabsorption   and Tubular secretion

Figure 1:Steps involved in urine formation.

Glomerular Filtration

During filtration, blood enters the afferent arteriole and flows into the glomerulus where filterable blood components, such as water and nitrogenous waste, will move towards the inside of the glomerulus, and nonfilterable components, such as cells and serum albumins, proteins  will exit via the efferent arteriole. These filterable components accumulate in the glomerulus to form the glomerular filtrate.

Glomerular filtration filters out most of the solutes due to high blood pressure and specialized membranes in the afferent arteriole. The blood pressure in the glomerulus is maintained independent of factors that affect systemic blood pressure. The “leaky” connections between the endothelial cells of the glomerular capillary network allow solutes to pass through easily. All solutes in the glomerular capillaries, except for macromolecules like proteins, pass through by passive diffusion. There is no energy requirement at this stage of the filtration process. Glomerular filtration rate (GFR) is the volume of glomerular filtrate formed per minute by the kidneys. GFR is regulated by multiple mechanisms and is an important indicator of kidney function.

Tubular Reabsorption and Secretion

1. Tubular reabsorption occurs in the PCT part of the renal tubule. Almost all nutrients are reabsorbed, and this occurs either by passive or active transport. Reabsorption of water and some key electrolytes are regulated and can be influenced by hormones. Sodium (Na ) is the most abundant ion and most of it is reabsorbed by active transport and then transported to the peritubular capillaries. Because Na is actively transported out of the tubule, water follows it to even out the osmotic pressure. Water is also independently reabsorbed into the peritubular capillaries due to the presence of aquaporins, or water channels, in the PCT. This occurs due to the low blood pressure and high osmotic pressure in the peritubular capillaries. However, every solute has a transport maximum and the excess is not reabsorbed

Figure 2: Countercurrent exchange in Loop of Henle

In the loop of Henle, the permeability of the membrane changes. The descending limb is permeable to water, not solutes; the opposite is true for the ascending limb. Additionally, the loop of Henle invades the renal medulla, which is naturally high in salt concentration and tends to absorb water from the renal tubule and concentrate the filtrate. The osmotic gradient increases as it moves deeper into the medulla. Because two sides of the loop of Henle perform opposing functions, as illustrated in Figure 2, it acts as a countercurrent multiplier. The vasa recta around it acts as the countercurrent exchanger.

The loop of Henle (seen in Figure 2) acts as a countercurrent multiplier that uses energy to create concentration gradients. The descending limb is water permeable. Water flows from the filtrate to the interstitial fluid, so osmolality inside the limb increases as it descends into the renal medulla. At the bottom, the osmolality is higher inside the loop than in the interstitial fluid. Thus, as filtrate enters the ascending limb, Na  and Cl− ions exit through ion channels present in the cell membrane. Further up, Na  is actively transported out of the filtrate and Cl− follows. Osmolarity is given in units of milliosmoles per liter (mOsm/L)

By the time the filtrate reaches the DCT, most of the urine and solutes have been reabsorbed. If the body requires additional water, all of it can be reabsorbed at this point. Further reabsorption is controlled by hormones, which will be discussed in a later section. Excretion of wastes occurs due to lack of reabsorption combined with tubular secretion. Undesirable products like metabolic wastes, urea, uric acid, and certain drugs, are excreted by tubular secretion. Most of the tubular secretion happens in the DCT, but some occurs in the early part of the collecting duct. Kidneys also maintain an acid-base balance by secreting excess H  ions.

Although parts of the renal tubules are named proximal and distal, in a cross-section of the kidney, the tubules are placed close together and in contact with each other and the glomerulus. This allows for exchange of chemical messengers between the different cell types. For example, the DCT ascending limb of the loop of Henle has masses of cells called macula densa, which are in contact with cells of the afferent arterioles called juxtaglomerular cells. Together, the macula densa and juxtaglomerular cells form the juxtaglomerular complex (JGC). The JGC is an endocrine structure that secretes the enzyme renin and the hormone erythropoietin. When hormones trigger the macula densa cells in the DCT due to variations in blood volume, blood pressure, or electrolyte balance, these cells can immediately communicate the problem to the capillaries in the afferent and efferent arterioles, which can constrict or relax to change the glomerular filtration rate of the kidneys.

By the time the filtrate reaches the DCT, most of the urine and solutes have been reabsorbed. If the body requires additional water, all of it can be reabsorbed at this point. Further reabsorption is controlled by hormones, which will be discussed in a later section. Excretion of wastes occurs due to lack of reabsorption combined with tubular secretion. Undesirable products like metabolic wastes, urea, uric acid, and certain drugs, are excreted by tubular secretion. Most of the tubular secretion happens in the DCT, but some occurs in the early part of the collecting duct. Kidneys also maintain an acid-base balance by secreting excess H ions.

Although parts of the renal tubules are named proximal and distal, in a cross-section of the kidney, the tubules are placed close together and in contact with each other and the glomerulus. This allows for exchange of chemical messengers between the different cell types. For example, the DCT ascending limb of the loop of Henle has masses of cells called macula densa, which are in contact with cells of the afferent arterioles called juxtaglomerular cells. Together, the macula densa and juxtaglomerular cells form the juxtaglomerular complex (JGC). The JGC is an endocrine structure that secretes the enzyme renin and the hormone erythropoietin. When hormones trigger the macula densa cells in the DCT due to variations in blood volume, blood pressure, or electrolyte balance, these cells can immediately communicate the problem to the capillaries in the afferent and efferent arterioles, which can constrict or relax to change the glomerular filtration rate of the kidneys.

Figure 3: Substances Filtered and Reabsorbed by the Nephron

Each part of the nephron seen in this figure performs a different function in filtering waste and maintaining homeostatic balance.

1. The glomerulus forces small solutes out of the blood by pressure.
2. The proximal convoluted tubule reabsorbs ions, water, and nutrients from the filtrate into the interstitial fluid (tubular reabsorption), and actively transports toxins and drugs from the interstitial fluid into the filtrate tubular secretion. The proximal convoluted tubule also adjusts blood pH by selectively secreting ammonia (NH3) into the filtrate, where it reacts with H  to form NH4 . The more acidic the filtrate, the more ammonia is secreted.
3. The descending loop of Henle is lined with cells containing aquaporins that  from the filtrate into the interstitial fluid.
4. In the thin part of the ascending loop of Henle, Na  and Cl− ions diffuse into the interstitial fluid. In the thick part, these same ions are actively transported into the interstitial fluid. Because salt but not water is lost, the filtrate becomes more dilute as it travels up the limb.
5. In the distal convoluted tubule, K  and H  ions are selectively secreted into the filtrate, while Na , Cl−, and HCO3− ions are reabsorbed to maintain pH and electrolyte balance in the blood.
6. The collecting duct reabsorbs solutes and water from the filtrate, forming dilute urine. (credit: modification of work by NIDDK)

A nephrologist studies and deals with diseases of the kidneys—both those that cause kidney failure (such as diabetes) and the conditions that are produced by kidney disease (such as hypertension). Blood pressure, blood volume, and changes in electrolyte balance come under the purview of a nephrologist.

Nephrologists usually work with other physicians who refer patients to them or consult with them about specific diagnoses and treatment plans. Patients are usually referred to a nephrologist for symptoms such as blood or protein in the urine, very high blood pressure, kidney stones, or renal failure.

Nephrology is a subspecialty of internal medicine. To become a nephrologist, medical school is followed by additional training to become certified in internal medicine. An additional two or more years is spent specifically studying kidney disorders and their accompanying effects on the body.