Kidneys

Definition: Kidneys are the organs that control the amount and composition of body water by separating the blood into waste products (which leave the body as urine) and nutrients (which are returned to the blood).

Anatomy or system affected: Abdomen, circulatory system, urinary system

Specialties and related fields:Hematology, nephrology, urology

Structure and Functions

The normal human body has two kidneys, fist-sized organs located behind the abdomen and under the diaphragm. Each kidney, shaped like a bean, has a notch called the hilum, and the backbone separates the two kidneys. The kidneys make urine from blood. The renal artery transports blood into the kidney, while the renal vein transports blood out of the kidney. The blood vessels and the ureter connect with the kidney at its hilum.

The two kidneys are essentially identical in structure and function; consequently, kidney function can be discussed in the singular. The kidneys are a major functional unit of the circulatory system, unlike organs such as the brain, skin, or uterus, which are merely supported by that circulation. The kidney controls the environment of all cells of the body, an activity that is essential to life. That environment is salt water, and to understand the structure and function of the kidney, it is necessary to understand the nature of salt water in the body.

The human body is about 56 percent water, and the composition of this fluid is very important. One-third of this water is outside the cells; some of this extracellular fluid is between cells, and some of it is the liquid in blood vessels (blood is composed of liquid and cells). Two-thirds of the body's water is inside cells. The cell membrane surrounding each cell retains the intracellular fluid, but the water molecules move freely across the cell membrane. The size of each cell is determined by its water content. Cells swell or shrink based on the accumulation or loss of water molecules. The concentration of substances dissolved in the water determines whether water will accumulate inside or outside cells. Some of these dissolved substances are gases such as oxygen, hydrogen, and carbon dioxide; some are minerals such as sodium and calcium; some are sugars or proteins; and others are nutrients and waste products.

The amount and the composition of body water is controlled by the kidneys. Two other organs that aid in controlling the composition of body water are the lungs and the digestive tract; they can add or remove materials from the body water. The kidneys control the composition of body water primarily by removing materials from body water. Unlike the lungs and the digestive tract, however, the kidneys also regulate the amount of body water. The kidneys carry out both of these functions by acting on the blood. The kidney has three other important functions: It helps to control blood pressure, helps to control the manufacture of red blood cells, and participates in the manufacture of vitamin D. This article focuses on function of the normal kidney and what can make the kidney function abnormally.

Each kidney contains more than a million nephrons, its functional units, arranged in cones. A nephron is composed of blood vessels and a Bowman's capsule, a cup of renal cells containing the capillary tuft called a glomerulus and attached to a renal tubule.

A kidney has between eight and eighteen cones of nephrons. The base of each cone is near the surface of the kidney, and the peak of each cone is pointed at the renal pelvis, the central sac that collects and channels urine. Each nephron acts like a very sophisticated filtration system for the blood. Approximately 20 to 25 percent of all the blood in the body flows through the blood vessels of the kidneys every minute.

The action of the nephron actually begins with a porous filter, the glomerulus, that separates particles from a liquid. In this case, the liquid is blood plasma and the particles are blood cells and those protein molecules that are too large to pass through the glomerular pores. About 20 percent of the liquid in the blood seeps through the wall of glomeruli and into the inner space of Bowman's capsules. This liquid that crosses into a Bowman's capsule contains water, minerals, sugars, amino acids, and products of cell metabolism. The body needs to retain many of these substances, including water, so they must be recaptured by nephrons and returned to the blood.

The recapturing process occurs in the renal tubules. This is the process in which the nephron differs from an ordinary filter. The tubules have special cells that are capable of selectively reabsorbing those materials that must be retained by the body. These materials are passed from the liquid inside the tubules, through the tubule cells, and into blood capillaries that are laced or braided around the outside wall of the tubules. About 99 percent of the water molecules that seep into the renal tubules from the glomeruli are returned to the blood. The substances that do not need to be retained by the body continue to flow through the tubules and eventually leave the kidney as urine.

The mechanism in the renal tubular cells that selectively reabsorbs substances from the tubular liquid is quite special. The membrane of each cell contains proteins that act as chemical pumps. These pump proteins pick up substances to be reabsorbed from the tubular liquid and pass those substances into and through the tubular cells, where they enter renal capillaries. The reabsorbed substances may be salts or electrolytes, such as sodium or bicarbonate, or they may be sugars or even amino acids. As these substances are reabsorbed, much of the tubular water is also reabsorbed.

The pump proteins can work in the opposite direction as well. They can move substances from the renal capillaries surrounding the tubules, through the wall of the tubules, and into the tubular liquid. This process is called tubular secretion. Substances that commonly undergo tubular secretion are potassium, ammonium, and acid.

The remarkable action of the pump proteins requires fuel-in this case, adenosine triphosphate (ATP). ATP is made by living cells from oxygen, sugar, fatty acids, and nucleic acids in the blood. Pump proteins stop working when cells are unable to make ATP.

The pressure of the blood flow through the glomeruli and the reabsorption process of the renal tubules are closely controlled. This control takes place directly in the kidney, which contains sensing mechanisms that respond to changes in fluid composition. The kidney makes a hormone, called renin, that increases blood pressure. Other sensors that respond to changes in fluid composition are located in the brain. When these sensors detect changes that require action, the brain, acting through the pituitary gland, releases hormones, such as antidiuretic hormone (ADH), that act on the kidney. Another important hormone that controls kidney function, aldosterone, comes from the adrenal gland. The actual means by which these hormones control kidney function, however, is only partially understood.

By other mechanisms, the kidney detects whether the blood contains sufficient red blood cells (erythrocytes). Red blood cells are responsible for carrying oxygen to all the other cells in the body. When more red blood cells are needed, the kidney makes a hormone called erythropoietin, which stimulates the bone marrow and causes it to make more red blood cells.

Disorders and Diseases

The advantage of having a pair of kidneys becomes obvious if renal function becomes impaired. A person does quite well with one kidney; in fact, half of one kidney is sufficient to keep an individual alive.

A kidney problem may be suspected if an individual experiences changes in urination, such as pain on urination, changes in frequency of urination (more often or less often than usual), or changes in the urine that is formed (such as in its amount, appearance, or odor). Puffiness of the skin all over the body, but especially of the hands, feet, ankles, and face, may indicate abnormal renal function. This puffiness signifies water retention. Kidney disease can also be manifested by severe pain in the lower back, side, abdomen, or sex organs. The pain may be long-lasting or may occur with startling suddenness.

A person can be born with abnormal kidneys; this is a form of kidney disease. Normal kidneys, however, can malfunction because of a problem in the kidney itself, a problem in the blood circulation, or a problem in the flow of urine from the kidneys. Examples of abnormal kidneys at birth, abnormal urinary flow (kidney stones), and kidney infection will be discussed.

The formation of the kidneys by a fetus is quite complex and is controlled by genes. The development of the kidneys, other parts of the urinary tract (the ureters, bladder, and urethra), and the sex organs are all closely related. There are many opportunities for the developmental process to go wrong. Sometimes no kidneys are formed, sometimes the two kidneys are fused together, and sometimes more than one pair of kidneys is formed.

One of the most common malformations of the kidney is polycystic kidney disease, a hereditary (genetic) disorder affecting about 2 in 1,000 people. In the United States, it is ten times more common than sickle cell disease and fifteen times more common than cystic fibrosis. In polycystic kidney disease, each kidney contains numerous fluid-filled sacs, or cysts, scattered throughout the organ. The cysts are of different sizes, some very small and some the size of a grape. Polycystic kidneys are noticeably enlarged.

The cysts are caused by a malformation of the renal tubules. A cyst is formed when a renal tubule develops a branch from the main tubule. Tubules are not supposed to form branches; if this occurs, however, then the branch may become sealed off from the original tubule so that it has no entrance or exit. These sealed-off tubules are the cysts. They are capable of secretory activity because their cells contain pump proteins. The cysts enlarge as they accumulate fluid, putting pressure on the blood vessels, their capillaries, and the nephrons. The flow of blood and of urine is hindered. Patients with polycystic kidney disease often develop high blood pressure, kidney stones, and kidney infections. The disease can begin before birth, but symptoms may not occur until childhood or early adulthood. The intensity or severity of the disease varies greatly, from symptomless to life-threatening. Treatment of mild polycystic kidney disease may consist of relieving the pain, curing the infection, and controlling the blood pressure. Treatment of severe or life-threatening polycystic renal disease requires dialysis or kidney transplantation.

Stones in the urinary tract are very common. About 1 in 100 Americans has stones, and 1 in 1,000 adults experiences such severe symptoms that hospitalization is required. Kidney stones are caused by a prolonged high concentration of certain minerals in the urine, usually calcium, oxalate, or urate. The stones usually consist of crystals bound together by proteins.

The size and shape of kidney stones vary greatly. They may be microscopic or the size of a pea or even larger; they may be smooth or jagged. The stones may be passed from the urinary tract during urination, but some require removal by a urologist. Microscopic stones may not cause any symptoms, while larger stones can be very painful and may produce blood in the urine. Because stones hinder the flow of urine, their presence can allow bacteria to grow in the urinary tract, producing an infection.

Kidney stones that produce symptoms and are not passed by the patient must be removed. Some stones may be removed with a ureteroscope while the patient is under general anesthesia. A ureteroscope is a urological instrument like a hollow tube. It is inserted into the urinary tract through the external opening of the urethra and passed through the bladder and into the ureter. The tube can actually be inserted into the renal pelvis. The optical system of the ureteroscope allows the physician to see inside the urinary tract. Through the ureteroscope, kidney stones may be broken up (a process known as lithotripsy) by applying ultrasonic, laser, or electrohydraulic (acoustic shock-wave) energy.

An alternative means of removing large kidney stones is extracorporeal shock-wave lithotripsy, or ESWL. ESWL is desirable because it uses shock waves to break up the stones, thus eliminating the need to insert medical instruments into the patient. In one method of ESWL, the anesthetized patient is placed in a tub of water. X-ray imaging locates and monitors the stones as shock waves crush them. The patient's tissues are not damaged, and the sandy remains of the stones are then passed with urine. The development of ESWL has offered a useful means of treating kidney stones, but it has not eliminated the need for surgical or ureteroscopic removal of these stones from some patients. Each patient and each stone is different; they require the professional evaluation of a urologist.

Urinary tract infections are common, affecting 10 to 20 percent of women at some point in their lives; they are less common in men. Pathogens usually infect the kidneys by ascending the urinary tract via the urethra, bladder, and ureters. The normal bladder is an effective barrier to these infections, but any obstruction to the flow of urine, such as enlarged prostate, renal cysts, pregnancy, or a urinary stone, will weaken this barrier. Sometimes, pathogens infect the kidneys through the blood. Most urinary tract infections can be effectively treated with antibiotics. It is important for the physician to choose an antibiotic that is effective against the causative pathogen. Each antibiotic is effective against only a few types of bacteria, and many different bacteria can cause urinary tract infections.

Infections involving the kidney are especially serious. Because the kidneys are essential to life, these infections must be treated promptly and completely. Some infections affect the kidney even after the infection is cured. The body reacts to pathogens by producing proteins called antibodies, which circulate in the bloodstream. Antibodies in the blood can coat and damage the glomerular filters in Bowman's capsules. This reduces the effectiveness of the filters, allowing blood and protein to enter the urine and causing the body to become puffy. The medical term for this serious kidney disease is glomerulonephritis. Treatment is available, but it is better to prevent the disease from occurring. If left untreated, the kidney damage may be so extensive that dialysis or transplantation is required to prevent death from renal failure.

Perspective and Prospects

The ancient Greeks seem to be the earliest people whose writings about the kidney have survived. They had no regard for the importance of this organ, mainly because their frame of reference consisted of four "humors." Even before 500 BCE, the Greeks were developing the doctrine of the four elements of the inanimate universe: air, fire, water, and earth. From this idea, Polybus, the son-in-law of Hippocrates, created the corollary of the four "humors" responsible for life: yellow bile (choler), blood, phlegm (pituita), and black bile (melancholia). The concept of humors dominated the thinking of Aristotle (384-322 BCE) when he wrote about his study of the anatomy of kidneys in several animals, including humans. This approach delayed an understanding of even the basic concept that kidneys and urine are related, an idea finally proposed about 290 BCE by Erasistratus of Ceos.

Knowledge of Erasistratus comes mainly from Galen (129–c. 199 CE). Galen, rather than applauding the advances of his forebears, ridiculed unfounded assertions. He conducted physiological experiments on living animals, such as observing the effect of cutting and tying one ureter while leaving the opposite one intact. His experiments yielded much information about renal physiology. The writings of Galen formed the foundation of medical knowledge for the next four hundred years. Students and teachers, rather than building upon the experimental process, accepted the proclamations of Galen as dogma.

The next great advance in renal knowledge came from the Italian anatomist Bartolommeo Eustachio (1520–1574), who, without the benefit of a microscope, discovered the renal tubules and their relationship to the renal vascular system. His descriptions and drawings of 1564 were lost in the Vatican library until 1714. In the meantime, another Italian, Lorenzo Bellini (1643–1704), independently discovered the renal tubules and discerned their function. A contemporary, Marcello Malpighi (1628–1694), discovered glomeruli and their relationship to tubules.

Subsequent advances had to wait until the nineteenth century, when knowledge of all aspects of human biology and medicine began a rapid advance. Many independent advances in the nineteenth and twentieth centuries-in surgery, pharmacology, and immunology-made the transplantation of kidneys and other major organs possible. General anesthesia was developed independently by two Americans: by Crawford Long in 1842 and by William T. G. Morton in 1846. Antiseptic procedures were originated in 1867 by the Englishman Joseph Lister, and vascular surgical techniques were developed in 1902 by the French surgeon Alexis Carrel and the Hungarian surgeon Emerich Ullman. Anticoagulants were developed in 1914 and 1915, and systemic antibiotics were developed in the 1930s and 1940s. Blood typing was begun in Europe by Karl Landsteiner (1868–1943). Tissue immunology was first explained in 1953, and tissue typing was introduced in France and the United States in the 1960s. Immunosuppressive drugs were developed during this same period. Kidney transplantation is also possible because of extracorporeal support devices such as the dialysis machine, the heart-lung machine, and the organ perfusion machine.

The first transplant of a human kidney between identical twins was performed on December 23, 1954, by Joseph E. Murray. He later performed the first human kidney transplant between unrelated persons on April 5, 1962. By the 1990s, tens of thousands of kidney transplants were being performed in the United States every year. There are many more persons waiting for a transplant than there are kidneys available for transplantation. The solution to this problem is unclear. Transplants between living persons in the same family may be encouraged, and transplants from animals to humans may be perfected. It is even possible that a transplantable artificial kidney can be developed, but this task will be enormously difficult, considering all the functions of a natural kidney. Stem cell technology opened the potential for the growth of replacement kidneys and other organs in laboratories.

Key Terms

Bowman's capsule: the group of renal cells that forms the cup of a nephron; fluids that seep from glomerular capillaries into the hollow wall of the capsule will be transformed into urine during their passage through the renal tubule leading from the capsule

glomerulus: a tuft or ball of capillaries contained within a Bowman's capsule

nephron: the almost-microscopic functional unit of the kidney, composed of special capillary blood vessels and of a Bowman's capsule connected to a renal tubule; each kidney has approximately 1.2 million nephrons

renal: of or relating to the kidneys

renal pelvis: the central pocket or sac of each kidney, which collects urine from all nephrons and channels it into the ureter

renal tubule: the tubular portion of a nephron that allows renal fluid to flow from the Bowman's capsule to the renal pelvis; these tubules, shaped like hairpins, are crucially important in the production of urine

ureter: the tube that transports urine from the renal pelvis to the urinary bladder

Bibliography

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