A nervous system cell that provides support for neurons and helps them transmit nerve impulses.

Created by CK-12 Foundation/Adapted by Christine Miller

Pictured in Figure 16.4.1 is a steak and kidney pie; this savory dish is a British favorite. When kidneys are on a menu, they typically come from sheep, pigs, or cows. In these animals (as in the human animal), kidneys are the main organs of excretion.

The two bean-shaped kidneys are located high in the back of the abdominal cavity, one on each side of the spine. Both kidneys sit just below the diaphragm, the large breathing muscle that separates the abdominal and thoracic cavities. As you can see in the following figure, the right kidney is slightly smaller and lower than the left kidney. The right kidney is behind the liver, and the left kidney is behind the spleen. The location of the liver explains why the right kidney is smaller and lower than the left.

Kidney Anatomy

The shape of each kidney gives it a convex side (curving outward) and a concave side (curving inward). You can see this clearly in the detailed diagram of kidney anatomy shown in Figure 16.4.3. The concave side is where the renal artery enters the kidney, as well as where the renal vein and ureter leave the kidney. This area of the kidney is called the hilum. The entire kidney is surrounded by tough fibrous tissue — called the renal capsule — which, in turn, is surrounded by two layers of protective, cushioning fat.

Internally, each kidney is divided into two major layers: the outer renal cortex and the inner renal medulla (see Figure 16.4.3 above). These layers take the shape of many cone-shaped renal lobules, each containing renal cortex surrounding a portion of medulla called a renal pyramid. Within the renal pyramids are the structural and functional units of the kidneys, the tiny nephrons. Between the renal pyramids are projections of cortex called renal columns. The tip, or papilla, of each pyramid empties urine into a minor calyx (chamber). Several minor calyces empty into a major calyx, and the latter empty into the funnel-shaped cavity called the renal pelvis, which becomes the ureter as it leaves the kidney.

The renal circulation is an important part of the kidney’s primary function of filtering waste products from the blood. Blood is supplied to the kidneys via the renal arteries. The right renal artery supplies the right kidney, and the left renal artery supplies the left kidney. These two arteries branch directly from the aorta, which is the largest artery in the body. Each kidney is only about 11 cm (4.4 in) long, and has a mass of just 150 grams (5.3 oz), yet it receives about ten per cent of the total output of blood from the heart. Blood is filtered through the kidneys every 3 minutes, 24 hours a day, every day of your life.

As indicated in Figure 16.4.4, each renal artery carries blood with waste products into the kidney. Within the kidney, the renal artery branches into increasingly smaller arteries that extend through the renal columns between the renal pyramids. These arteries, in turn, branch into arterioles that penetrate the renal pyramids. Blood in the arterioles passes through nephrons, the structures that actually filter the blood. After blood passes through the nephrons and is filtered, the clean blood moves through a network of venules that converge into small veins. Small veins merge into increasingly larger ones, and ultimately into the renal vein, which carries clean blood away from the kidney to the inferior vena cava.

Figure 16.4.4 gives an indication of the complex structure of a nephron. The nephron is the basic structural and functional unit of the kidney, and each kidney typically contains at least a million of them. As blood flows through a nephron, many materials are filtered out of the blood, needed materials are returned to the blood, and the remaining materials form urine. Most of the waste products removed from the blood and excreted in urine are byproducts of metabolism. At least half of the waste is urea, a waste product produced by protein catabolism. Another important waste is uric acid, produced in nucleic acid catabolism.

Components of a Nephron

Figure 16.4.5 shows in greater detail the components of a nephron. Each nephron is composed of an initial filtering component that consists of a network of capillaries called the glomerulus (plural, glomeruli), which is surrounded by a space within a structure called glomerular capsule (also known as the Bowman's capsule). Extending from glomerular capsule is the renal tubule. The proximal end (nearest glomerular capsule) of the renal tubule is called the proximal convoluted (coiled) tubule. From here, the renal tubule continues as a loop (known as the loop of Henle) (also known as the loop of the nephron), which in turn becomes the distal convoluted tubule. The latter finally joins with a collecting duct. As you can see in the diagram, arterioles surround the total length of the renal tubule in a mesh called the peritubular capillary network.

Function of a Nephron

The simplified diagram of a nephron in Figure 16.4.6 shows an overview of how the nephron functions. Blood enters the nephron through an arteriole called the afferent arteriole. Next, some of the blood passes through the capillaries of the glomerulus. Any blood that doesn’t pass through the glomerulus — as well as blood after it passes through the glomerular capillaries — continues on through an arteriole called the efferent arteriole. The efferent arteriole follows the renal tubule of the nephron, where it continues playing a role in nephron functioning.

 

Filtration

As blood from the afferent arteriole flows through the glomerular capillaries, it is under pressure. Because of the pressure, water and solutes are filtered out of the blood and into the space made by glomerular capsule, almost like the water you cook pasta is is filtered out through a strainer. This is the filtration stage of nephron function. The filtered substances — called filtrate — pass into glomerular capsule, and from there into the proximal end of the renal tubule.  Anything too large to move through the pores in the glomerulus, such as blood cells, large proteins, etc., stay in the cardiovascular system.  At this stage, filtrate (fluid in the nephron) includes water, salts, organic solids (such as nutrients), and waste products of metabolism (such as urea).

Reabsorption and Secretion

As filtrate moves through the renal tubule, some of the substances it contains are reabsorbed from the filtrate back into the blood in the efferent arteriole (via peritubular capillary network). This is the reabsorption stage of nephron function and it is about returning "the good stuff" back to the blood so that it doesn't exit the body in urine. About two-thirds of the filtered salts and water, and all of the filtered organic solutes (mainly glucose and amino acids) are reabsorbed from the filtrate by the blood in the peritubular capillary network. Reabsorption occurs mainly in the proximal convoluted tubule and the loop of Henle, as seen in Figure 16.4.7.

At the distal end of the renal tubule, some additional reabsorption generally occurs. This is also the region of the tubule where other substances from the blood are added to the filtrate in the tubule. The addition of other substances to the filtrate from the blood is called secretion. Both reabsorption and secretion (shown in Figure 16.4.7) in the distal convoluted tubule are largely under the control of endocrine hormones that maintain homeostasis of water and mineral salts in the blood. These hormones work by controlling what is reabsorbed into the blood from the filtrate and what is secreted from the blood into the filtrate to become urine. For example, parathyroid hormone causes more calcium to be reabsorbed into the blood and more phosphorus to be secreted into the filtrate.

Collection of Urine and Excretion

By the time the filtrate has passed through the entire renal tubule, it has become the liquid waste known as urine. Urine empties from the distal end of the renal tubule into a collecting duct. From there, the urine flows into increasingly larger collecting ducts. As urine flows through the system of collecting ducts, more water may be reabsorbed from it. This will occur in the presence of antidiuretic hormone from the posterior pituitary gland. This hormone makes the collecting ducts permeable to water, allowing water molecules to pass through them into capillaries by osmosis, while preventing the passage of ions or other solutes. As much as 75% of the water may be reabsorbed from urine in the collecting ducts, making the urine more concentrated.

Urine finally exits the largest collecting ducts through the renal papillae. It empties into the renal calyces, and finally into the renal pelvis. From there, it travels through the ureter to the urinary bladder for eventual excretion from the body. An average of roughly 1.5 litres (a little over 6 cups) of urine is excreted each day. Normally, urine is yellow or amber in colour (see Figure 16.4.8). The darker the colour, generally speaking, the more concentrated the urine is.

 

Besides filtering blood and forming urine for excretion of soluble wastes, the kidneys have several vital functions in maintaining body-wide homeostasis. Most of these functions are related to the composition or volume of urine formed by the kidneys. The kidneys must maintain the proper balance of water and salts in the body, normal blood pressure, and the correct range of blood pH. Through the processes of absorption and secretion by nephrons, more or less water, salt ions, acids, or bases are returned to the blood or excreted in urine, as needed, to maintain homeostasis.

Blood Pressure Regulation

The kidneys do not control homeostasis all alone. As indicated above, endocrine hormones are also involved. Consider the regulation of blood pressure by the kidneys. Blood pressure is the pressure exerted by blood on the walls of the arteries. The regulation of blood pressure is part of a complex system, called the renin-angiotensin-aldosterone system. This system regulates the concentration of sodium in the blood to control blood pressure.

The renin-angiotensin-aldosterone system is put into play when the concentration of sodium ions in the blood falls lower than normal. This causes the kidneys to secrete an enzyme called renin into the blood. It also causes the liver to secrete a protein called angiotensinogen. Renin changes angiotensinogen into a proto-hormone called angiotensin I. This is converted to angiotensin II by an enzyme (angiotensin-converting enzyme) in lung capillaries.

Angiotensin II is a potent hormone that causes arterioles to constrict. This, in turn, increases blood pressure. Angiotensin II also stimulates the secretion of the hormone aldosterone from the adrenal cortex. Aldosterone causes the kidneys to increase the reabsorption of sodium ions and water from the filtrate into the blood. This returns the concentration of sodium ions in the blood to normal. The increased water in the blood also increases blood volume and blood pressure.

Other Kidney Hormones

Hormones other than renin are also produced and secreted by the kidneys. These include calcitriol and erythropoietin.

• Calcitriol is secreted by the kidneys in response to low levels of calcium in the blood. This hormone stimulates uptake of calcium by the intestine, thus raising blood levels of calcium.
• Erythropoietin is secreted by the kidneys in response to low levels of oxygen in the blood. This hormone stimulates erythropoiesis, which is the production of  erythrocytes in bone marrow. Extra red blood cells increase the level of oxygen carried in the blood.

Kidney failure is a complication of common disorders including diabetes mellitus and hypertension. It is estimated that approximately 12.5% of Canadians have some form of kidney disease.  If the disease is serious, the patient must either receive a donated kidney or have frequent hemodialysis, a medical procedure in which the blood is artificially filtered through a machine. Transplant generally results in better outcomes than hemodialysis, but demand for organs far outstrips the supply. The average time on the organ donation waitlist for a kidney is four years.  There are over 3,000 Canadians on the wait list for a kidney transplant and some will die waiting for a kidney to become available.

For the past decade, Dr. William Fissell, a kidney specialist at Vanderbilt University, has been working to create an implantable part-biological and part-artificial kidney. Using microchips like those used in computers, he has produced an artificial kidney small enough to implant in the patient’s body in place of the failed kidney. According to Dr. Fissell, the artificial kidney is “... a bio-hybrid device that can mimic a kidney to remove enough waste products, salt, and water to keep a patient off [hemo]dialysis.”

The filtration system in the artificial kidney consists of a stack of 15 microchips. Tiny pores in the microchips act as a scaffold for the growth of living kidney cells that can mimic the natural functions of the kidney. The living cells form a membrane to filter the patient’s blood as a biological kidney would, but with less risk of rejection by the patient’s immune system, because they are embedded within the device. The new kidney doesn’t need a power source, because it uses the natural pressure of blood flowing through arteries to push the blood through the filtration system. A major part of the design of the artificial organ was devoted to fine tuning the fluid dynamics so blood flows through the device without clotting.

Because of the potential life-saving benefits of the device, the implantable kidney was given fast-track approval for testing in people by the U.S. Food and Drug Administration. The artificial kidney is expected to be tested in pilot trials by 2018. Dr. Fissell says he has a long list of patients eager to volunteer for the trials.

Attributions

Figure 16.4.1

Steak and Kidney Pie by Charles Haynes on Flickr is used under a CC BY-SA 2.0 (https://creativecommons.org/licenses/by-sa/2.0/) license.

Figure 16.4.2

Gray Kidneys by Henry Vandyke Carter (1831-1897) on Wikimedia Commons is in the  public domain (https://en.wikipedia.org/wiki/public_domain). (Bartleby.com: Gray’s Anatomy, Plate 1120).

Figure 16.4.3

Blausen_0592_KidneyAnatomy_01 by BruceBlaus on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 16.4.4

Diagram_showing_how_the_kidneys_work_CRUK_138.svg by Cancer Research UK on Wikimedia Commons is used under a CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0) license.

Figure 16.4.5

Blood_Flow_in_the_Nephron by OpenStax College on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 16.4.6

1024px-Physiology_of_Nephron by Madhero88 on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 16.4.7

Nephron_Secretion_Reabsorption by OpenStax College on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 16.4.8

Urine by User:Markhamilton at English Wikipedia on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

Figure 16.4.9

Renin_Angiotensin_System-01 by OpenStax College on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

References

Betts, J. G., Young, K.A., Wise, J.A., Johnson, E., Poe, B., Kruse, D.H., Korol, O., Johnson, J.E., Womble, M., DeSaix, P. (2013, June 19). Figure 25.10 Blood flow in the nephron [digital image].  In Anatomy and Physiology (Section 25.3). OpenStax. https://openstax.org/books/anatomy-and-physiology/pages/25-3-gross-anatomy-of-the-kidney

Betts, J. G., Young, K.A., Wise, J.A., Johnson, E., Poe, B., Kruse, D.H., Korol, O., Johnson, J.E., Womble, M., DeSaix, P. (2013, June 19). Figure 25.17 Locations of secretion and reabsorption in the nephron [digital image].  In Anatomy and Physiology (Section 25.6). OpenStax. https://openstax.org/books/anatomy-and-physiology/pages/25-6-tubular-reabsorption

Betts, J. G., Young, K.A., Wise, J.A., Johnson, E., Poe, B., Kruse, D.H., Korol, O., Johnson, J.E., Womble, M., DeSaix, P. (2013, June 19). Figure 26.14 The renin-angiotensin system [digital image].  In Anatomy and Physiology (Section 26.3). OpenStax. https://openstax.org/books/anatomy-and-physiology/pages/26-3-electrolyte-balance

Blausen.com Staff. (2014). Medical gallery of Blausen Medical 2014. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436

Hamada Abass. (2013). Urine formation. YouTube. https://www.youtube.com/watch?v=es-t8lO1KpA&feature=youtu.be

TED-Ed. (2015, February 9). How do your kidneys work? - Emma Bryce. YouTube. https://www.youtube.com/watch?v=FN3MFhYPWWo&feature=youtu.be

TED-Ed. (2013, March 15). Printing a human kidney - Anthony Atala. YouTube. https://www.youtube.com/watch?v=bX3C201O4MA&feature=youtu.be

 

Created by CK-12 Foundation/Adapted by Christine Miller

Why do dogs pee on fire hydrants? Besides “having to go,” they are marking their territory with chemicals in their urine called pheromones. It’s a form of communication, in which they are “saying” with odors that the yard is theirs and other dogs should stay away. In addition to fire hydrants, dogs may urinate on fence posts, trees, car tires, and many other objects. Urination in dogs, as in people, is usually a voluntary process controlled by the brain. The process of forming urine — which occurs in the kidneys — occurs constantly, and is not under voluntary control. What happens to all the urine that forms in the kidneys? It passes from the kidneys through the other organs of the urinary system, starting with the ureters.

As shown in Figure 16.5.2, ureters are tube-like structures that connect the kidneys with the urinary bladder. They are paired structures, with one ureter for each kidney. In adults, ureters are between 25 and 30 cm (about 10–12 in) long and about 3 to 4 mm in diameter.

Each ureter arises in the pelvis of a kidney (the renal pelvis in Figure 16.5.3). It then passes down the side of the kidney, and finally enters the back of the bladder. At the entrance to the bladder, the ureters have sphincters that prevent the backflow of urine.

The walls of the ureters are composed of multiple layers of different types of tissues.  The innermost layer is a special type of epithelium, called transitional epithelium. Unlike the epithelium lining most organs, transitional epithelium is capable of stretching and does not produce mucus. It lines much of the urinary system, including the renal pelvis, bladder, and much of the urethra, in addition to the ureters. Transitional epithelium allows these organs to stretch and expand as they fill with urine or allow urine to pass through. The next layer of the ureter walls is made up of loose connective tissue containing elastic fibres, nerves, and blood and lymphatic vessels. After this layer are two layers of smooth muscles, an inner circular layer, and an outer longitudinal layer. The smooth muscle layers can contract in waves of peristalsis to propel urine down the ureters from the kidneys to the urinary bladder. The outermost layer of the ureter walls consists of fibrous tissue.

The urinary bladder is a hollow, muscular, and stretchy organ that rests on the pelvic floor. It collects and stores urine from the kidneys before the urine is eliminated through urination. As shown in Figure 16.5.4, urine enters the urinary bladder from the ureters through two ureteral openings on either side of the back wall of the bladder. Urine leaves the bladder through a sphincter called the internal urethral sphincter. When the sphincter relaxes and opens, it allows urine to flow out of the bladder and into the urethra.

Like the ureters, the bladder is lined with transitional epithelium, which can flatten out and stretch as needed as the bladder fills with urine. The next layer (lamina propria) is a layer of loose connective tissue, nerves, and blood and lymphatic vessels. This is followed by a submucosa layer, which connects the lining of the bladder with the detrusor muscle in the walls of the bladder. The outer covering of the bladder is peritoneum, which is a smooth layer of epithelial cells that lines the abdominal cavity and covers most abdominal organs.

The detrusor muscle in the wall of the bladder is made of smooth muscle fibres controlled by both the autonomic and somatic nervous systems. As the bladder fills, the detrusor muscle automatically relaxes to allow it to hold more urine. When the bladder is about half full, the stretching of the walls triggers the sensation of needing to urinate. When the individual is ready to void, conscious nervous signals cause the detrusor muscle to contract, and the internal urethral sphincter to relax and open. As a result, urine is forcefully expelled out of the bladder and into the urethra.

The urethra is a tube that connects the urinary bladder to the external urethral orifice, which is the opening of the urethra on the surface of the body. As shown in Figure 16.5.5, the urethra in males travels through the penis, so it is much longer than the urethra in females. In males, the urethra averages about 20 cm (about 7.8 in) long, whereas in females, it averages only about 4.8 cm (about 1.9 in) long. In males, the urethra carries semen (as well as urine), but in females, it carries only urine.  In addition, in males, the urethra passes through the prostate gland (part of the reproductive system) which is absent in women.

Like the ureters and bladder, the proximal (closer to the bladder) two-thirds of the urethra are lined with transitional epithelium. The distal (farther from the bladder) third of the urethra is lined with mucus-secreting epithelium. The mucus helps protect the epithelium from urine, which is corrosive. Below the epithelium is loose connective tissue, and below that are layers of smooth muscle that are continuous with the muscle layers of the urinary bladder. When the bladder contracts to forcefully expel urine, the smooth muscle of the urethra relaxes to allow the urine to pass through.

In order for urine to leave the body through the external urethral orifice, the external urethral sphincter must relax and open. This sphincter is a striated muscle that is controlled by the somatic nervous system, so it is under conscious, voluntary control in most people (exceptions are infants, some elderly people, and patients with certain injuries or disorders). The muscle can be held in a contracted state and hold in the urine until the person is ready to urinate. Following urination, the smooth muscle lining the urethra automatically contracts to re-establish muscle tone, and the individual consciously contracts the external urethral sphincter to close the external urethral opening.

Attributions

Figure 16.5.1

Cliche by Jackie on Wikimedia Common s is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0) license.

Figure 16.5.2

Urinary System Male by BruceBlaus on Wikimedia Commons is used under a CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0) license.

Figure 16.5.3

Adrenal glands on Kidney by NCI Public Domain by Alan Hoofring (Illustrator) /National Cancer Institute (photo ID 4355) on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

Figure 16.5.4

2605_The_Bladder by OpenStax College on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license. (Micrograph originally provided by the Regents of the University of Michigan Medical School © 2012.)

Figure 16.5.5

512px-Male_and_female_urethral_openings.svg by andrybak (derivative work) on Wikimedia Commons is used under a CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) license. (Original: Male anatomy blank.svg: alt.sex FAQ, derivative work: Tsaitgaist Female anatomy with g-spot.svg: Tsaitgaist.)

References

Betts, J. G., Young, K.A., Wise, J.A., Johnson, E., Poe, B., Kruse, D.H., Korol, O., Johnson, J.E., Womble, M., DeSaix, P. (2013, June 19). Figure 25.4 Bladder (a) Anterior cross section of the bladder. (b) The detrusor muscle of the bladder (source: monkey tissue) LM × 448 [digital image].  In Anatomy and Physiology (Section 7.3). OpenStax. https://openstax.org/books/anatomy-and-physiology/pages/25-2-gross-anatomy-of-urine-transport 

SciShow. (2016, January 22). What happens when you hold your pee? YouTube. https://www.youtube.com/watch?v=dg4_deyHLvQ&feature=youtu.be

TED. (2016, September 2). The taboo secret to better health | Molly Winter. YouTube. https://www.youtube.com/watch?v=2Brajdazp1o&feature=youtu.be

Created by CK-12 Foundation/Adapted by Christine Miller

Awareness ribbons are symbols meant to show support or to raise consciousness for a cause. Different colours are associated with different issues, often relating to health problems. The first ribbon to gain familiarity for a health issue was the red ribbon for HIV/AIDS, created in 1991. The pink ribbon for breast cancer awareness is probably the best known today. Do you know what a green ribbon like the one pictured in Figure 16.6.1 represents? Among several other health problems, a green ribbon is meant to show support or raise awareness for kidney disorders.

The kidneys play such vital roles in eliminating wastes and toxins — and in maintaining body-wide homeostasis — that disorders of the kidneys may be life threatening. Gradual loss of normal kidney function commonly occurs with a number of disorders, including diabetes mellitus and high blood pressure. Other disorders of the kidneys are caused by faulty inherited genes. Loss of kidney function may eventually progress to kidney failure.

Diabetic Nephropathy

Diabetic nephropathy is a progressive kidney disease caused by damage to the capillaries in the glomeruli of the kidneys, due to long-standing diabetes mellitus (see Figure 16.6.2). It is not fully understood how diabetes leads to damage of glomerular capillaries, but it is thought that high levels of glucose in the blood are involved. In people with diabetes, diabetic nephropathy is more likely if blood glucose is poorly controlled. Having high blood pressure, a history of cigarette smoking, and a family history of kidney problems are additional risk factors. Diabetic nephropathy often has no symptoms at first. In fact, it may take up to a decade after kidney damage begins for symptoms to appear. When they do appear, they typically include severe tiredness, headaches, nausea, frequent urination, and itchy skin.

Proteins are large molecules that are usually not filtered out of blood in the glomeruli. When the glomerular capillaries are damaged, it allows proteins (such as albumin) to leak into the filtrate from the blood. As a result, albumin ends up being excreted in the urine. Finding a high level of albumin in the urine is one indicator of diabetic nephropathy and helps to diagnose the disorder. Drugs may be prescribed to reduce protein levels in the urine. Controlling high blood sugar levels and hypertension (high blood pressure) is also important to help slow kidney damage, as is a reduction of sodium intake.

Polycystic Kidney Disease

Polycystic kidney disease (PKD) is a genetic disorder in which multiple abnormal cysts develop and grow in the kidneys. Figure 16.6.3 shows a pair of kidneys that are riddled with cysts from PKD. In people who inherit PKD, the cysts may start to form at any point in life, from infancy through adulthood. Typically, both kidneys are affected. Symptoms of the disorder may include high blood pressure, headaches, abdominal pain, blood in the urine, and excessive urination.

There are two types of PKD. The more common type is caused by an autosomal dominant allele, and the less common type is caused by an autosomal recessive allele. Both types together make PKD one of the most common hereditary diseases in Canada, affecting one in every 500 people. There is little or no difference in the rate of occurrence of PKD between genders or ethnic groups. Other than a kidney transplant, there is no known cure for this disease.

Kidney Failure

Both diabetic nephropathy and PKD may lead to kidney (or renal) failure(classified as end-stage kidney disease), in which the kidneys are no longer able to adequately filter metabolic wastes from the blood. Long-term, uncontrolled high blood pressure is another common cause of kidney failure. Symptoms of kidney failure may include nausea, more or less frequent urination, blood in the urine, muscle cramps, anemia, swelling of the extremities, and shortness of breath due to the accumulation of fluid in the lungs. If kidney function drops below the level needed to sustain life, then the only treatment option is kidney transplantation or some means of artificial filtration of the blood, such as by hemodialysis.

Hemodialysis is a medical procedure in which blood is filtered externally through a machine. You can see how it works in Figure 16.6.4. During dialysis, waste products (such as urea) are removed — along with excess water — from the patient’s blood before the blood is returned to the patient. Hemodialysis is typically done on an outpatient basis in a hospital or special dialysis clinic. Less frequently, it is done in the patient’s home. Depending on the patient’s size, among other factors, the blood is filtered for three to four hours roughly three times a week.

Kidney Stones

A kidney stone, (pictured in Figure 16.6.5) also known as a renal calculus, is a solid crystal that forms in a kidney from minerals in urine (see Figure 16.6.6). The majority of kidney stones consist of crystals of calcium salts. Kidney stones typically leave the body in the urine stream. A small stone may go undetected, because it can pass through the ureters and other urinary tract organs without causing symptoms. A larger stone may cause pain when it passes through the urinary tract. If a kidney stone grows large enough, it may block the ureter. Blockage of a ureter may cause a decrease in kidney function and damage to the kidney.

A kidney stone that causes pain is generally treated with pain medication, such as opiates, until it passes through the urinary tract. A stone that causes a blockage may be treated with lithotripsy. This is a medical procedure in which high-intensity ultrasound pulses are applied externally to cause fragmentation of the stone into pieces small enough to pass easily through the urinary tract. Although lithotripsy is noninvasive, it can cause damage to the kidneys. An alternative treatment for a stone that blocks urine flow is to insert a stent into the ureter to expand it and allow both urine and the stone to pass. In some cases, surgery may be required to physically remove a large stone from the ureter.  In minor cases, sometimes drinking apple cider vinegar or lemon juice can break down small kidney stones because of the citric acid these foods contain.

A combination of lifestyle and genetic factors seem to predispose certain people to develop kidneys stones. Risk factors include high consumption of cola soft drinks, eating a diet high in animal protein, being overweight, and not drinking enough fluids. Preventive measures are obvious. They include limiting cola consumption, eating less animal protein, losing weight, and increasing fluid intake.

Although disorders of the kidneys are generally the most serious urinary system disorders, problems that affect other organs of the urinary tract are generally more common. They include bladder infections and urinary incontinence.

Bladder Infection

A bladder infection, also called cystitis, is a very common type of urinary tract infection in which the urinary bladder becomes infected by bacteria (typically E. coli), and rarely by fungi. Symptoms of bladder infections may include pain with urination, frequent urination, and feeling the need to urinate despite having an empty bladder. In some cases, there may be blood in the urine. A much less common type of urinary tract infection is pyelonephritis, in which the kidney becomes infected. If a kidney infection occurs, it is generally because of an untreated bladder infection. Bladder infections are treated mainly with antibiotics.

Risk factors for urinary bladder infections include sexual intercourse, improper toileting technique, diabetes, obesity, and — most notably — female sex. Bladder infections are four times more common in women than in men. For women, they are the most common type of bacterial infections, and as many as one in ten women have a bladder infection in any given year. Female anatomy explains the sex difference in the incidence of bladder infections. The urethra is much shorter and closer to the anus in females than in males, so contamination of the urethra and then the bladder with GI tract bacteria is more likely in females than in males. Once the bacteria reach the bladder, they can attach to the bladder wall and form a biofilm that resists the body’s immune response.

Urinary Incontinence

Urinary incontinence is a chronic problem of uncontrolled leakage of urine. It is very common, especially at older ages, and especially in women. Sometimes, urinary incontinence is a sign of another health problem, such as diabetes or obesity. Regardless of the underlying cause, the symptoms of urinary incontinence alone may have a large impact on quality of life, frequently causing inconvenience, embarrassment, and distress.

In men, urinary incontinence is most commonly caused by an enlarged prostate gland or treatment for prostate cancer. In women, there are two common types of urinary incontinence with different causes: stress incontinence and urge incontinence.

• Stress urinary incontinence is caused by loss of support of the urethra, usually due to stretching of pelvic floor muscles during childbirth. It is characterized by leakage of small amounts of urine with activities that increase abdominal pressure, such as coughing, sneezing, or lifting. Treatment of stress urinary incontinence may include Kegel exercises to strengthen the pelvic muscles. More serious cases may call for surgery to improve support for the bladder.
• Urge urinary incontinence (commonly called “overactive bladder”) is caused by uncontrolled contractions of the detrusor muscle in the wall of the bladder. This causes the bladder to empty unexpectedly. Urge incontinence is characterized by leakage of large amounts of urine in association with insufficient warning to get to the bathroom in time. Treatment of urge incontinence may include taking a medication to relax the detrusor muscle.

You probably have had to “donate” a urine specimen for analysis in conjunction with a medical visit. A thorough medical exam often includes clinical tests for urine. Understanding what your urine can reveal about your health may help you appreciate the need for such tests.

The most common urine test is called urinalysis. In a routine urinalysis, a urine sample may be analyzed by sight and smell, and with simple urine test strips. If a particular disorder is suspected, urinalysis may be more extensive. The urine may be analyzed with specific tests or viewed under a microscope to identify abnormal substances in the urine. If a bacterial infection is suspected, a sample of urine may be cultured in the lab to see if it grows bacteria, and which type of bacteria grow. Knowing the type of bacteria is important for deciding which class of antibiotics is likely to be most effective in treating the infection.

The colour and clarity of urine may be obvious first indicators of disorders or other abnormalities. Normal urine is yellow to amber in colour, and looks clear. If urine is nearly colourless, it could be a sign of excessive fluid intake, or it might be a sign of diabetes. Very dark urine may indicate dehydration, but it could also be caused by taking certain medications or ingesting some other substances. If urine has a reddish tinge, it is often a sign of blood in the urine, which could be due to a urinary tract infection, kidney stone, or even cancer. If urine appears cloudy instead of clear, it could be due to white blood cells in the urine, which may be another sign of a urinary tract infection.

If it is very diluted, normal urine may have virtually no odor. It will have a stronger odor if it is concentrated. Brief changes in the normal odor of urine often occur due to the ingestion of certain foods or medications. After eating asparagus, for example, urine may have a peculiar and distinctive odor for several hours. More significant is urine that has a sweet smell, because this may indicate sugar in the urine, which is a sign of diabetes.

Urine test strips (shown in Figure 16.6.7), much like the familiar litmus test strips used to detect acids and bases in chemistry lab, are used to identify abnormal levels of certain components in the urine. For example, urine test strips can detect and quantify the presence of nitrites in urine, which is usually a sign of infection with certain types of bacteria. Urine test strips can also be used to identify proteins such as albumin in urine, which may be a sign of a kidney infection or of kidney failure. Levels of sodium in urine can also be measured with test strips, and higher-than-normal levels may be another indication of kidney failure. In addition, test strips can identify and quantify the presence of white blood cells and blood in a urine specimen, both of which are likely to be a sign of a urinary tract infection or some other urinary system disorder.

Besides the use of urine test strips, other simple urine tests that are often performed include Benedict’s test, which is a test for the presence and quantity of glucose in urine. If the level is high, it likely indicates diabetes. The test is so simple that it may even be done by the patient at home to monitor how well sugar levels are being controlled. Testing for some other substances in urine requires the patient to collect urine over a 24-hour period. This is the case when testing for the adrenal hormone cortisol. When urine cortisol levels are higher than normal, it may indicate Cushing’s syndrome. When the levels are lower than normal, it may indicate Addison’s disease.

Attributions

Figure 16.6.1

512px-Green_ribbon.svg by MesserWoland on Wikimedia Commons is used under a CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0/) license.

Figure 16.6.2

1024px-Blausen_0310_DiabeticNephropathy by BruceBlaus on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 16.6.3

1024px-Polycystic_kidneys,_gross_pathology_CDC_PHIL by Dr. Edwin P. Ewing, Jr. / CDC's Public Health Image Library (PHIL) #861. on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

Figure 16.6.4

1000px-Hemodialysis-en.svg by User:YassineMrabet on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 16.6.5

512px-Kidney_stone_1 by User:Михајло Анђелковић on Wikimedia Commons is used under a CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) license.

Figure 16.6.6

Blausen_0595_KidneyStones by BruceBlaus on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 16.6.7

Amanda Cotton – Urinalysis Test Strips by Dominic Alves on Flickr is used under a  CC BY 2,0 (https://creativecommons.org/licenses/by/2.0/) license.

References

Alila Medical Media. (2016, September 8). Urinary tract infections, animation. YouTube. https://www.youtube.com/watch?v=lY2bZjggc08&feature=youtu.be

Blausen.com Staff. (2014). Medical gallery of Blausen Medical 2014. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436.

Michelle Kenway. (2013, February 1). Kegel exercises beginners workout for women. YouTube. https://www.youtube.com/watch?v=wRKhtfbJHdo&feature=youtu.be

TED-Ed. (2017, July 3). What causes kidney stones? - Arash Shadman. YouTube. https://www.youtube.com/watch?v=W0GpIMNTPYg&feature=youtu.be

Updated Canadian expert consensus published to guide optimal management of ADPKD. (2018, December 18). PDK Foundation of Canada. https://www.endpkd.ca/canadian_expert_consensus_2018

Created by CK-12 Foundation/Adapted by Christine Miller

Twenty-six-year-old Hakeem wasn’t feeling well. He was more tired than usual, dragging through his workdays despite going to bed earlier, and napping on the weekends. He didn’t have much of an appetite, and had started losing weight. When he pressed on the side of his neck, like the doctor is doing in Figure 17.1.1, he noticed an unusual lump.

Hakeem went to his doctor, who performed a physical exam and determined that the lump was a swollen lymph node. Lymph nodes are part of the immune system, and they will often become enlarged when the body is fighting off an infection. Dr. Hayes thinks that the swollen lymph node and fatigue could be signs of a viral or bacterial infection, although he is concerned about Hakeem’s lack of appetite and weight loss. All of those symptoms combined can indicate a type of cancer called lymphoma. An infection, however, is a more likely cause, particularly in a young person like Hakeem. Dr. Hayes prescribes an antibiotic in case Hakeem has a bacterial infection, and advises him to return in a few weeks if his lymph node does not shrink, or if he is not feeling better.

Hakeem returns a few weeks later. He is not feeling better and his lymph node is still enlarged. Dr. Hayes is concerned, and orders a biopsy of the enlarged lymph node. A lymph node biopsy for suspected lymphoma often involves the surgical removal of all or part of a lymph node. This helps to determine whether the tissue contains cancerous cells.

The initial results of the biopsy indicate that Hakeem does have lymphoma. Although lymphoma is more common in older people, young adults and even children can get this disease. There are many types of lymphoma, with the two main types being Hodgkin's lymphoma and non-Hodgkin's lymphoma. Non-Hodgkin lymphoma (NHL), in turn, has many subtypes. The subtype depends on several factors, including which cell types are affected. Some subtypes of NHL, for example, affect immune system cells called B cells, while others affect different immune system cells called T cells.

Dr. Hayes explains to Hakeem that it is important to determine which type of lymphoma he has, in order to choose the best course of treatment. Hakeem’s biopsied tissue will be further examined and tested to see which cell types are affected, as well as which specific cell-surface proteins — called antigens — are present. This should help identify his specific type of lymphoma.

As you read this chapter, you will learn about the functions of the immune system, and the specific roles that its cells and organs — such as B and T cells and lymph nodes — play in defending the body. At the end of this chapter, you will learn what type of lymphoma Hakeem has and what some of his treatment options are, including treatments that make use of the biochemistry of the immune system to fight cancer with the immune system itself.

Attributions

Figure 17.1.1

Lymph nodes/Is it a Cold or the Flu  by Lee Health on Vimeo is used under Vimeo's Terms of Service (https://vimeo.com/terms#licenses).

Figure 17.1.2

mitchell-luo-ymo_yC_N_2o-unsplash [photo] by Mitchell Luo on Unsplash is used under the Unsplash License (https://unsplash.com/license).

Figure 17.1.3

Lymph node biopsy by US Army Africa on Flickr is used under a  CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/) license.

References

Mayo Clinic Staff. (n.d.). Hodgkin's lymphoma [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/hodgkins-lymphoma/symptoms-causes/syc-20352646

Mayo Clinic Staff. (n.d.). Non-Hodgkin's lymphoma [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/non-hodgkins-lymphoma/symptoms-causes/syc-20375680

 

 

Created by CK-12 Foundation/Adapted by Christine Miller

The white patches on either side of the throat in Figure 17.3.1 are signs of tonsillitis. The tonsils are small structures in the throat that are very common sites of infection. The white spots on the tonsils pictured here are evidence of infection. The patches consist of large amounts of dead bacteria, cellular debris, and white blood cells — in a word: pus. Children with recurrent tonsillitis may have their tonsils removed surgically to eliminate this type of infection. The tonsils are organs of the lymphatic system.

The lymphatic system is a collection of organs involved in the production, maturation, and harboring of white blood cells called lymphocytes. It also includes a network of vessels that transport or filter the fluid known as lymph in which lymphocytes circulate. Figure 17.3.2 shows major lymphatic vessels and other structures that make up the lymphatic system. Besides the tonsils, organs of the lymphatic system include the thymus, the spleen, and hundreds of lymph nodes distributed along the lymphatic vessels.

The lymphatic vessels form a transportation network similar in many respects to the blood vessels of the cardiovascular system. However, unlike the cardiovascular system, the lymphatic system is not a closed system. Instead, lymphatic vessels carry lymph in a single direction — always toward the upper chest, where the lymph empties from lymphatic vessels into blood vessels.

The return of lymph to the bloodstream is one of the major functions of the lymphatic system. When blood travels through capillaries of the cardiovascular system, it is under pressure, which forces some of the components of blood (such as water, oxygen, and nutrients) through the walls of the capillaries and into the tissue spaces between cells, forming tissue fluid, also called interstitial fluid (see Figure 17.3.3). Interstitial fluid bathes and nourishes cells, and also absorbs their waste products. Much of the water from interstitial fluid is reabsorbed into the capillary blood by osmosis. Most of the remaining fluid is absorbed by tiny lymphatic vessels called lymph capillaries. Once interstitial fluid enters the lymphatic vessels, it is called lymph. Lymph is very similar in composition to blood plasma. Besides water, lymph may contain proteins, waste products, cellular debris, and pathogens. It also contains numerous white blood cells, especially the subset of white blood cells known as lymphocytes. In fact, lymphocytes are the main cellular components of lymph.

The lymph that enters lymph capillaries in tissues is transported through the lymphatic vessel network to two large lymphatic ducts in the upper chest. From there, the lymph flows into two major veins (called subclavian veins) of the cardiovascular system. Unlike blood, lymph is not pumped through its network of vessels. Instead, lymph moves through lymphatic vessels via a combination of contractions of the vessels themselves and the forces applied to the vessels externally by skeletal muscles, similarly to how blood moves through veins. Lymphatic vessels also contain numerous valves that keep lymph flowing in just one direction, thereby preventing backflow.

Lymphatic vessels called lacteals (see Figure 17.3.4) are present in the lining of the gastrointestinal tract, mainly in the small intestine. Each tiny villus in the lining of the small intestine has an internal bed of capillaries and lacteals. The capillaries absorb most nutrients from the digestion of food into the blood. The lacteals absorb mainly fatty acids from lipid digestion into the lymph, forming a fatty-acid-enriched fluid called chyle. Vessels of the lymphatic network then transport chyle from the small intestine to the main lymphatic ducts in the chest, from which it drains into the blood circulation. The nutrients in chyle then circulate in the blood to the liver, where they are processed along with the other nutrients that reach the liver directly via the bloodstream.

The primary immune function of the lymphatic system is to protect the body against pathogens and cancerous cells. This function of the lymphatic system is centred on the production, maturation, and circulation of lymphocytes. Lymphocytes are leukocytes that are involved in the adaptive immune system. They are responsible for the recognition of — and tailored defense against — specific pathogens or tumor cells. Lymphocytes may also create a lasting memory of pathogens, so they can be attacked quickly and strongly if they ever invade the body again. In this way, lymphocytes bring about long-lasting immunity to specific pathogens.

There are two major types of lymphocytes, called B cells and T cells. Both B cells and T cells are involved in the adaptive immune response, but they play different roles.

Production and Maturation of Lymphocytes

Like all other types of blood cells (including erythrocytes), both B cells and T cells are produced from stem cells in the red marrow inside bones. After lymphocytes first form, they must go through a complicated maturation process before they are ready to search for pathogens. In this maturation process, they “learn” to distinguish self from non-self. Only those lymphocytes that successfully complete this maturation process go on to actually fight infections by pathogens.

B cells mature in the bone marrow, which is why they are called B cells. After they mature and leave the bone marrow, they travel first to the circulatory system and then enter the lymphatic system to search for pathogens. T cells, on the other hand, mature in the thymus, which is why they are called T cells. The thymus is illustrated in Figure 17.3.5. It is a small lymphatic organ in the chest that consists of an outer cortex and inner medulla, all surrounded by a fibrous capsule. After maturing in the thymus, T cells enter the rest of the lymphatic system to join B cells in the hunt for pathogens. The bone marrow and thymus are called primary lymphoid organs because of their role in the production and/or maturation of lymphocytes.

Lymphocytes in Secondary Lymphoid Organs

The tonsils, spleen, and lymph nodes are referred to as secondary lymphoid organs. These organs do not produce or mature lymphocytes. Instead, they filter lymph and store lymphocytes. It is in these secondary lymphoid organs that pathogens (or their antigens) activate lymphocytes and initiate adaptive immune responses. Activation leads to cloning of pathogen-specific lymphocytes, which then circulate between the lymphatic system and the blood, searching for and destroying their specific pathogens by producing antibodies against them.

Tonsils

There are four pairs of human tonsils. Three of the four are shown in Figure 17.3.6. The fourth pair, called tubal tonsils, is located at the back of the nasopharynx. The palatine tonsils are the tonsils that are visible on either side of the throat. All four pairs of tonsils encircle a part of the anatomy where the respiratory and gastrointestinal tracts intersect, and where pathogens have ready access to the body. This ring of tonsils is called Waldeyer's ring.

Spleen

The spleen (Figure 17.3.7) is the largest of the secondary lymphoid organs, and is centrally located in the body. Besides harboring lymphocytes and filtering lymph, the spleen also filters blood. Most dead or aged erythrocytes are removed from the blood in the red pulp of the spleen. Lymph is filtered in the white pulp of the spleen. In the fetus, the spleen has the additional function of producing red blood cells. This function is taken over by bone marrow after birth.

Lymph Nodes

Each lymph node is a small, but organized collection of lymphoid tissue (see Figure 17.3.8) that contains many lymphocytes. Lymph nodes are located at intervals along the lymphatic vessels, and lymph passes through them on its way back to the blood.

There are at least 500 lymph nodes in the human body. Many of them are clustered at the base of the limbs and in the neck. Figure 17.3.9 shows the major lymph node concentrations, and includes the spleen and the region named Waldeyer’s ring, which consists of the tonsils.

When lymph nodes become enlarged and tender to the touch, they are obvious signs of immune system activity. Because it is easy to see and feel swollen lymph nodes, they are one way an individual can monitor his or her own health. To be useful in this way, it is important to know the myths and realities about swollen lymph nodes.

 

Myth	Reality
"You should see a doctor immediately whenever you have swollen lymph nodes."	Lymph nodes are constantly filtering lymph, so it is expected that they will change in size with varying amounts of debris or pathogens that may be present. A minor, unnoticed infection may cause swollen lymph nodes that may last for a few weeks. Generally, lymph nodes that return to their normal size within two or three weeks are not a cause for concern.
"Swollen lymph nodes mean you have a bacterial infection."	Although an infection is the most common cause of swollen lymph nodes, not all infections are caused by bacteria. Mononucleosis, for example, commonly causes swollen lymph nodes, and it is caused by viruses. There are also other causes of swollen lymph nodes besides infections, such as cancer and certain medications.
"A swollen lymph node means you have cancer."	Cancer is far less likely to be the cause of a swollen lymph node than is an infection. However, if a lymph node remains swollen longer than a few weeks — especially in the absence of an apparent infection — you should have your doctor check it.
"Cancer in a lymph node always originates somewhere else. There is no cancer of the lymph nodes."	Cancers do commonly spread from their site of origin to nearby lymph nodes and then to other organs, but cancer may also originate in the lymph nodes. This type of cancer is called lymphoma.

 

Attributions

Figure 17.3.1

512px-Tonsillitis by Michaelbladon at English Wikipedia on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).  (Transferred from en.wikipedia to Commons by Kauczuk)

Figure 17.3.2

Blausen_0623_LymphaticSystem_Female by BruceBlaus  on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 17.3.3

2201_Anatomy_of_the_Lymphatic_System (cropped) by OpenStax College on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 17.3.4

1000px-Intestinal_villus_simplified.svg by Snow93 on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

Figure 17.3.5

2206_The_Location_Structure_and_Histology_of_the_Thymus by OpenStax College on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 17.3.6

Blausen_0861_Tonsils&Throat_Anatomy2 by BruceBlaus  on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 17.3.7

Figure_42_02_14 by CNX OpenStax on Wikimedia Commons is used under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0) license.

Figure 17.3.8

Illu_lymph_node_structure by NCI/ SEER Training on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain). (Archives: https://web.archive.org/web/20070311015818/http://training.seer.cancer.gov/module_anatomy/unit8_2_lymph_compo1_nodes.html)

Figure 17.3.9

1000px-Lymph_node_regions.svg by Fred the Oyster (derivative work) on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain). (Original by NCI/ SEER Training)

References

Betts, J. G., Young, K.A., Wise, J.A., Johnson, E., Poe, B., Kruse, D.H., Korol, O., Johnson, J.E., Womble, M., DeSaix, P. (2013, June 19). Figure 21.2 Anatomy of the lymphatic system [digital image].  In Anatomy and Physiology (Section 21.1). OpenStax. https://openstax.org/books/anatomy-and-physiology/pages/21-1-anatomy-of-the-lymphatic-and-immune-systems

Betts, J. G., Young, K.A., Wise, J.A., Johnson, E., Poe, B., Kruse, D.H., Korol, O., Johnson, J.E., Womble, M., DeSaix, P. (2013, June 19). Figure 21.7 Location, structure, and histology of the thymus [digital image].  In Anatomy and Physiology (Section 21.1). OpenStax. https://openstax.org/books/anatomy-and-physiology/pages/21-1-anatomy-of-the-lymphatic-and-immune-systems

Blausen.com Staff. (2014). Medical gallery of Blausen Medical 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436

Compton Care. (2016, March 7). What is lymphoedema or lymphedema? YouTube. https://www.youtube.com/watch?v=RMLPwOiYnII&feature=youtu.be

OpenStax. (2016, May 27) Figure 14. The spleen is similar to a lymph node but is much larger and filters blood instead of lymph [digital image]. In Open Stax, Biology (Section 42.2). OpenStax CNX.  https://cnx.org/contents/GFy_h8cu@10.8:etZobsU-@6/Adaptive-Immune-Response

Simple Nursing. (2015, June 28). Spleen physiology What does the spleen do in 2 minutes. YouTube. https://www.youtube.com/watch?v=ah74jT00jBA&feature=youtu.be

University Hospitals Bristol and Weston NHS FT. (2020, May 13). How to check your lymph nodes. YouTube. https://www.youtube.com/watch?v=L4KexZZAdyA&feature=youtu.be

 

A joint in which the opposing bony surfaces are covered with a layer of hyaline cartilage or fibrocartilage and in which some degree of free movement is possible.

Created by CK-12 Foundation/Adapted by Christine Miller

Eyes that are red, watery, and itchy are typical of an allergic reaction known as allergic rhinitis. Commonly called hay fever, allergic rhinitis is an immune system reaction, typically to the pollen of certain plants. Your immune system usually protects you from pathogens and keeps you well. However, like any other body system, the immune system itself can develop problems. Sometimes, it responds to harmless foreign substances as though they were pathogens. This is the basis of allergies like hay fever.

An allergy is a disorder in which the immune system makes an inflammatory response to a harmless antigen. It occurs when the immune system is hypersensitive to an antigen in the environment that causes little or no response in most people. Allergies are strongly familial. Allergic parents are more likely to have allergic children, and those children’s allergies are likely to be more severe, which is evidence that there is a heritable tendency to develop allergies. Allergies are more common in children than adults, because many children outgrow their allergies by adulthood.

Allergens

Any antigen that causes an allergy is called an allergen. Common allergens are plant pollens, dust mites, mold, specific foods (such as peanuts or shellfish), insect stings, and certain common medications (such as aspirin and penicillin). Allergens may be inhaled or ingested, or they may come into contact with the skin or eyes. Symptoms vary depending on the type of exposure, and the severity of the immune system response. Some of the most common causes of allergies are shown in Figure 17.6.2: latex, pollen, dust mites, pet dander, insect stings and various foods. Inhaling pollen may cause symptoms of allergic rhinitis, such as sneezing and red itchy eyes. Insect stings may cause an itchy rash. This type of allergy is called contact dermatitis.

Prevalence of Allergies

There has been a significant increase in the prevalence of allergies over the past several decades, especially in the rich nations of the world, where allergies are now very common disorders. In the developed countries, about 20% of people have or have had hay fever, another 20% have had contact dermatitis, and about 6% have food allergies. In the poorer nations of the world, on the other hand, allergies of all types are much less common.

One explanation for the rise in allergies in the developed world is the hygiene hypothesis. According to this hypothesis, people in developed countries live in relatively sterile environments because of hygienic practices and sanitation systems. As a result, people in these countries are exposed to fewer pathogens than their immune system evolved to cope with. To compensate, their immune system “keeps busy” by attacking harmless antigens in allergic responses.

How Allergies Occur

The diagram in Figure 17.6.3 shows how an allergic reaction occurs. At the first exposure to an allergen, B cells are activated to form plasma cells that produce large amounts of antibodies to the allergen. These antibodies attach to leukocytes called mast cells. Subsequently, every time the person encounters the allergen again, the mast cells are already primed and ready to deal with it. The primed mast cells immediately release cytokines and histamines, which in turn cause inflammation and recruitment of leukocytes, among other responses. These responses are responsible for the signs and symptoms of allergies.

Treating Allergies

The symptoms of allergies can range from mild to life-threatening. Mild allergy symptoms are often treated with antihistamines. These are drugs that reduce or eliminate the effects of the histamines that produce allergy symptoms.

Treating Anaphylaxis

The most severe allergic reaction is a systemic reaction called anaphylaxis. This is a life-threatening response caused by a massive release of histamines. Many of the signs and symptoms of anaphylaxis are shown in Figure 17.6.4. Some of them include a drop in blood pressure, changes in heart rate, shortness of breath, and swelling of the tongue and throat, which may threaten the patient with suffocation unless emergency treatment is given. People who have had anaphylactic reactions may carry an epinephrine autoinjector (widely known by its brand name EpiPen®) so they can inject themselves with epinephrine if they start to experience an anaphylactic response. The epinephrine helps control the immune reaction until medical care can be provided. Epinephrine constricts blood vessels to increase blood pressure, relaxes smooth muscles in the lungs to reduce wheezing and improve breathing, modulates heart rate, and works to reduce swelling that may otherwise block the airways.

Immunotherapy for Allergies

Another way to treat allergies is called immunotherapy, commonly called “allergy shots.” This approach may actually cure specific allergies, at least for several years if not permanently. It may be particularly beneficial for allergens that are difficult or impossible to avoid (such as pollen). First, however, patients must be tested to identify the specific allergens that are causing their allergies. As shown in Figure 17.6.5, this may involve scratching tiny amounts of common allergens into the skin, and then observing whether there is a localized reaction to any of them. Each allergen is applied in a different numbered location on the skin, so if there is a reaction — such as redness or swelling — the responsible allergens can be identified. Then, through periodic injections (usually weekly or monthly), patients are gradually exposed to larger and larger amounts of the allergens. Over time, generally from months to years, the immune system becomes desensitized to the allergens. This method of treating allergies is often effective for allergies to pollen or insect stings, but its usefulness for allergies to food is unclear.

Autoimmune Diseases

Autoimmune diseases occur when the immune system fails to recognize the body’s own molecules as self. As a result, instead of ignoring the body’s healthy cells, it attacks them, causing damage to tissues and altering organ growth and function. Most often, B cells are at fault for autoimmune responses. They are generally the cells that lose tolerance for self. Why does this occur? Some autoimmune diseases are thought to be caused by exposure to pathogens that have antigens similar to the body’s own molecules. After this exposure, the immune system responds to body cells as though they were pathogens, as well.

Certain individuals are genetically susceptible to developing autoimmune diseases. These individuals are also more likely to develop more than one such disease. Gender is a risk factor for autoimmunity — females are much more likely than males to develop autoimmune diseases. This is likely due, in part, to gender differences in sex hormones.

At a population level, autoimmune diseases are less common where infectious diseases are more common. The hygiene hypothesis has been proposed to explain the inverse relationship between infectious and autoimmune diseases, as well as the prevalence of allergies. According to the hypothesis, without infectious diseases to “keep it busy,” the immune system may attack the body’s own cells instead.

Common Autoimmune Diseases

An estimated 15 million or more people worldwide have one or more autoimmune diseases. Two of the most common autoimmune diseases are type I diabetes and multiple sclerosis. In terms of the specific body cells that are attacked by the immune system, both are localized diseases. In the case of type I diabetes, the immune system attacks and destroys insulin-secreting islet cells in the pancreas. In the case of multiple sclerosis, the immune system attacks and destroys the myelin sheaths that normally insulate the axons of neurons and allow rapid transmission of nerve impulses.

Some relatively common autoimmune diseases are systemic — or body-wide — diseases. They include rheumatoid arthritis and systemic lupus erythematosus (SLE). In these diseases, the immune system may attack and injure many tissues and organs. For example, as you can see in Figure 17.6.6, symptoms of SLE may involve the muscular, skeletal, integumentary, respiratory, and cardiovascular systems.

Treatment for Autoimmune Diseases

None of these common autoimmune diseases can be cured, although all of them have treatments that may help relieve symptoms and prevent some of the long-term damage they may cause. Traditional treatments for autoimmune diseases include immunosuppressive drugs to block the immune response, as well as anti-inflammatory drugs to quell inflammation. Hormone replacement may be another option. Type I diabetes, for example, is treated with injections of the hormone insulin, because islet cells in the pancreas can no longer secrete it.

Immunodeficiency occurs when the immune system is not working properly, generally because one or more components of the immune system are inactive. As a result, the immune system may be unable to fight off pathogens or cancers that a normal immune system would be able to resist. Immunodeficiency may occur for a variety of reasons.

Causes of Immunodeficiency

Dozens of rare genetic diseases can result in a defective immune system. This type of immunodeficiency is called primary immunodeficiency. One is born with one of these diseases, rather than acquiring it after birth. Probably the best known of these primary immunodeficiency diseases is severe combined immunodeficiency (SCID). It is also known as “bubble boy disease,” because people with this disorder are extremely vulnerable to infectious diseases, and some of them have become well known for living inside a bubble that provides a sterile environment. SCID is most often caused by an X-linked recessive mutation that interferes with normal B cell and T cell production.

Other types of immunodeficiency are not present at birth, but are acquired due to experiences or exposures that occur after birth. Acquired immunodeficiency is called secondary immunodeficiency because it is secondary to some other event or exposure. Secondary immunodeficiency may occur for a number of different reasons:

• Some pathogens attack and destroy immune system cells. An example is the virus known as HIV, which attacks and destroys T cells.
• The immune system naturally becomes less effective as people get older. This age-related decline — called immunosenescence — generally begins around the age of 50 and worsens with increasing age. Immunosenescence is the reason older people are generally more susceptible to disease than younger people.
• The immune system may be damaged by another disorder, such as obesity, alcoholism, or the abuse of other drugs.
• In developing countries, malnutrition is the most common cause of immune system damage and immunodeficiency. Inadequate protein intake is especially damaging to the immune system. It can lead to impaired complement system activity, phagocyte malfunction, and lower-than-normal production of antibodies and cytokines.
• Certain medications can suppress the immune system. This is the intended effect of immunosuppressant drugs given to people with transplanted organs so they do not reject them. In many cases, however, immunosuppression is an unwanted side effect of drugs used to treat other disorders.

Human immunodeficiency virus (HIV) is the most common cause of immunodeficiency in the world today. HIV infections of human hosts are a relatively recent phenomenon. Scientists think that the virus originally infected monkeys, but then jumped to human populations. most likely from a bite, probably sometime during the early to mid-1900s. This most likely occurred in West Africa, but the virus soon spread around the world. HIV was first identified by medical researchers in 1981. Since then, HIV has killed almost 40 million people worldwide, and its economic toll has also been enormous. The hardest hit countries are in Africa, where the virus has infected human populations the longest, and medications to control the virus are least available.  In 2016, over 63,000 Canadians were living with HIV.

HIV Transmission

HIV is transmitted through direct contact of mucous membranes or body fluids such as blood, semen, or breast milk. As shown in Figure 17.6.7, transmission of the virus can occur through sexual contact or the use of contaminated hypodermic needles. It can also be transmitted from an infected mother’s blood during late pregnancy or childbirth, or through breast milk after birth. In the past, HIV was also transmitted occasionally through blood transfusions. Because donated blood is now screened for HIV, the virus is no longer transmitted this way.

HIV and the Immune System

HIV infects and destroys helper T cells, the type of lymphocytes that regulate the immune response. This process is illustrated in the diagram in Figure 17.6.8. The virus injects its own DNA into a helper T cell and uses the T cell’s “machinery” to make copies of itself. In the process, the helper T cell is destroyed, and the virus copies go on to infect other helper T cells. HIV is able to evade the immune system and keep destroying helper T cells by mutating frequently so its surface antigens keep changing, and by using the host cell’s membrane to hide its own antigens.

Acquired immunodeficiency syndrome (AIDS) may result from years of damage to the immune system by HIV. It occurs when helper T cells fall to a very low level and opportunistic diseases occur. Opportunistic diseases are infections and tumors that are rare, except in people with a damaged immune system. The diseases take advantage of the “opportunity” presented by people whose immune system cannot fight back. Opportunistic diseases are usually the direct cause of death for people with AIDS.

Treating HIV/AIDS

For patients who have access to HIV medications, infection with the virus is no longer the death sentence that it once was. By 1995, combinations of drugs called “highly active antiretroviral therapy” were developed. For some patients, these drugs can reduce the amount of virus they are carrying to undetectable levels. However, some level of virus always hides in the body’s immune cells, and it will multiply again if a patient stops taking the medications. Researchers are trying to develop drugs to kill these hidden viruses, as well. If their efforts are successful, it could end AIDS.

EpiPens® and their sole manufacturer (pharmaceutical company Mylan) were featured in headlines in 2016, but not for a good reason. The media outburst was triggered by a drastic price hike in EpiPens® — and Mylan’s apparent greed.

EpiPens® are auto-injectable syringes preloaded with a measured dose of epinephrine, a drug that can rapidly stop a life-threatening anaphylactic response to an allergen. Using the device is easy and does not require any special training. The injector just needs to be jammed against the thigh, which can be done through clothing or on bare skin. Each year, doctors write millions of prescriptions for EpiPens®. Many people with severe allergies always carry two of the devices with them, just in case they experience anaphylaxis, although most of them never need to use them. Other people with severe allergies have literally had their lives saved multiple times by EpiPens® when they had anaphylactic reactions. Even when the devices haven’t been used, they must be replaced each year due to expiration of the epinephrine.

You might think that EpiPens® would be relatively inexpensive, given their life-saving potential. As recently as 2009, a two-pack of EpiPens® cost about $100. However, in just seven years, the cost of the same two-pack of EpiPens® skyrocketed by an incredible 400%! By 2016, the cost was $600 or more. Mylan apparently raised the price for the sole purpose of increasing profits. The company also raised prices significantly on many other drugs. The price hike in EpiPens® alone was certainly profitable. In 2015, the sale of EpiPens® earned Mylan $1 billion. Mylan’s CEO took home almost $19 million the same year, which was an increase of more than 600% over her prior salary.

News coverage of the price hike in EpiPens® began in the summer of 2016 after a price increase in May of that year. Both private citizens and elected officials expressed outrage over the price increase, especially when coupled with the gluttonous profits of the company and its CEO. By late August, Mylan responded to the backlash by offering discount coupons for EpiPens®. A few days later, the company promised to introduce a cheaper, generic version of the device. Analysts quickly determined that selling a generic version would allow Mylan to make more money on the product than reducing the price of the name-brand device, which they still declined to do. By September of 2016, Mylan was being investigated for antitrust violations related to sales of EpiPens® to public schools in New York City.

The Mylan/EpiPen® story may still be making the news. But whatever its outcome, the story has already added fuel to public and private debates about important ethical issues — issues such as the excessive costs of life-saving drugs and the huge profits of big pharma. What is the most recent news on EpiPens® and Mylan? If you are interested, you can check the headlines online to find out. What are your views on the ethical issues they raise?

 

Attributions

Figure 17.6.1

Oedema by Championswimmer on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/en:public_domain).

Figure 17.6.2

• Medical (latex) gloves from pngimg.com is used under a CC BY-NC 4.0 (https://creativecommons.org/licenses/by-nc/4.0/) license.
• House dust mites (5247996458) by Gilles San Martin from Namur, Belgium on Wikimedia Commons is used under a CC BY-SA 2.0 (https://creativecommons.org/licenses/by-sa/2.0/deed.en) license.
•  Honey bee macro by Karunakar Rayker on Flickr is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/) license.
• Peanuts by Karolina Grabowska on Pexels is used under a CC0 1.0 Universal Public Domain Dedication license (https://creativecommons.org/publicdomain/zero/1.0/).
• Photo of dog and grey cat by ERC4N51 on pxhere is used under a CC0 1.0 Universal Public Domain Dedication license (https://creativecommons.org/publicdomain/zero/1.0/).
• Tags: Pollen Allergy Spring by Castagnari53 on Pixabay, is used under the Pixabay License (https://pixabay.com/service/license/).

Figure 17.6.3

512px-Mast_cells by National Institute of Allergy and Infectious Diseases (U.S.) & National Cancer Institute (p.29) is in the public domain (https://en.wikipedia.org/wiki/en:public_domain).

Figure 17.6.4

Signs_and_symptoms_of_anaphylaxis by Mikael Häggström on Wikimedia Commons is used under a CC0 1.0 Universal Public Domain Dedication license (https://creativecommons.org/publicdomain/zero/1.0/).

Figure 17.6.5

Allergy Tests by Dan Pupius on Flickr is used under a CC BY-NC-SA 2.0 (https://creativecommons.org/licenses/by-nc-sa/2.0/) license.

Figure 17.6.6

1024px-Symptoms_of_SLE by Mikael Häggström on Wikimedia Commons is used under a CC0 1.0 Universal Public Domain Dedication license (https://creativecommons.org/publicdomain/zero/1.0/).

Figure 17.6.7

HIV transmission by CK-12 Foundation is used under a CC BY NC 3.0 (https://creativecommons.org/licenses/by-nc/3.0/) license.

Figure 17.6.8

HIV life cycle by CK-12 Foundation is used under a CC BY NC 3.0 (https://creativecommons.org/licenses/by-nc/3.0/) license.

©CK-12 Foundation Licensed under  • Terms of Use • Attribution

Figure 17.6.9

Epipen by Stock Catalog on flickr by Stock Catalog on Flickr is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/) license.

References

Brainard, J/ CK-12 Foundation. (2016). Figure 8 HIV may be transmitted in all of the ways shown here [digital image]. In CK-12 College Human Biology (Section 19.6) [online Flexbook]. CK12.org. https://www.ck12.org/book/ck-12-human-biology/section/19.6/

Brainard, J/ CK-12 Foundation. (2016). Figure 9 This diagram shows how HIV infects and destroys helper T cells [digital image]. In CK-12 College Human Biology (Section 19.6) [online Flexbook]. CK12.org. https://www.ck12.org/book/ck-12-human-biology/section/19.6/

CBS News. (2016, August 16). Rising cost of potentially life-saving EpiPen puts pinch on families [online article]. CBS Interactive Inc. https://www.cbsnews.com/news/allergy-medication-epipen-epinephrine-rising-costs-impact-on-families/

Gross Science. (2015, June 29). What are tonsil stones? | Gross Science. YouTube. https://www.youtube.com/watch?v=RiMSmDBvgto&feature=youtu.be

Häggström, M. (2014). Medical gallery of Mikael Häggström 2014. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436

National Institute of Allergy and Infectious Diseases (NIAID). (n.d.). Severe combined immunodeficiency (SCID) [online article]. National Institute of Health (NIH). https://www.niaid.nih.gov/diseases-conditions/severe-combined-immunodeficiency-scid

National Institute of Allergy and Infectious Diseases (U.S.) & National Cancer Institute (U.S.). (2003, September). Understanding the immune system and how it works [NIH Publication No. 03-5423]. Scholar Works -  Indiana University. https://scholarworks.iupui.edu/handle/1805/748

[The] New York Times. (2015, December 15). The boy in the bubble | Retro Report | The New York Times. YouTube. https://www.youtube.com/watch?v=pJa6KVLwl9U&feature=youtu.be

Seeker. (2014, October 3). Why are peanut allergies becoming so common? YouTube. https://www.youtube.com/watch?v=Mjr9h_QmdeM&feature=youtu.be

Summary: Estimates of HIV incidence, prevalence, and Canada's progress on meeting the 90-90-90 HIV targets 2016. (2018, July). Public Health Agency of Canada. https://www.canada.ca/content/dam/phac-aspc/documents/services/publications/diseases-conditions/summary-estimates-hiv-incidence-prevalence-canadas-progress-90-90-90/pub-eng.pdf

Swetlitz, I., Silverman, E. (2016, August 25). Mylan may have violated antitrust law in its EpiPen sales to schools, legal experts say [online article]. STATNews.com. https://www.statnews.com/2016/08/25/mylan-antitrust-epipen-schools/

TED-Ed. (2016, May 26). Why do people have seasonal allergies? - Eleanor Nelsen. YouTube.  https://www.youtube.com/watch?v=-q7Fz7NIMWM&feature=youtu.be

TED-Ed. (2015, March 16). Why it’s so hard to cure HIV/AIDS - Janet Iwasa, https://www.youtube.com/watch?v=0TipTogQT3E&feature=youtu.be

 

Created by CK-12 Foundation/Adapted by Christine Miller

These people are participating in a bike ride to raise funds for leukemia and lymphoma research (Figure 17.7.1). Leukemia and lymphoma are blood cancers. In 2020,  approximately 6,900 Canadians will be diagnosed with leukemia and 3,000 will die from this cancer. Lymphoma is the most common type of blood cancer. As a lymphoma patient, Hakeem, who you learned about in the beginning of this chapter, may eventually benefit from research funded by a bike ride like this one.

What type of blood cell is affected in lymphoma? As the name implies, lymphoma is a cancer that affects lymphocytes, which are a type of leukocyte. As you have learned in this chapter, there are different types of lymphocytes, including the B and T cells of the adaptive immune system. Different types of lymphoma affect different types of lymphocytes in different ways. It is important to correctly identify the type of lymphoma, so that patients can be treated appropriately.

You may recall that one of Hakeem’s symptoms was a swollen lymph node, and he was diagnosed with lymphoma after a biopsy of that lymph node. Swollen lymph nodes are a common symptom of lymphoma. As you have learned, lymph nodes are distributed throughout the body along lymphatic vessels, as part of the lymphatic system. The lymph nodes filter lymph and store lymphocytes. Therefore, they play an important role in fighting infections. Because of this, they will often swell in response to an infection. In Hakeem’s case, the swelling and other symptoms did not improve after several weeks and a course of antibiotics, which caused Dr. Hayes to suspect lymphoma instead. The biopsy showed that Hakeem did indeed have cancerous lymphocytes in his lymph nodes.

But which type of lymphocytes were affected? Lymphoma most commonly affects B or T lymphocytes. The two major types of lymphoma are called Hodgkin (HL) or non-Hodgkin lymphoma (NHL). NHL is more common than HL. In 2020, the Canadian Cancer Society estimates 10,400 Canadians will be diagnosed with non-Hodgkin lymphoma, whereas 1,000 will be diagnosed with Hodgkin lymphoma. While HL is one distinct type of lymphoma, NHL has about 60 different subtypes, depending on which specific cells are affected and how.

Hakeem was diagnosed with a type of NHL called diffuse large B-cell lymphoma (DLBCL) — the most common type of NHL. This type of lymphoma affects B cells and causes them to appear large under the microscope. In addition to Hakeem’s symptoms of fatigue, swollen lymph nodes, loss of appetite, and weight loss, common symptoms of this type of lymphoma include fever and night sweats. It is an aggressive and fast-growing type of lymphoma that is fatal if not treated. The good news is that with early detection and proper treatment, about 70% of patients with DLBCL can be cured.

How do physicians determine the specific type of lymphoma? Tissue obtained from a biopsy can be examined under a microscope to observe physical changes (such as abnormal cell size or shape) that are characteristic of a particular subtype of lymphoma. Additionally, tests can be performed on the tissue to determine which cell-surface antigens are present. Recall that antigens are molecules that bind to specific antibodies. Antibodies can be produced in the laboratory and labeled with compounds that can be identified by their colour under a microscope. When these antibodies are applied to a tissue sample, this colour will appear wherever the antigen is present, because it binds to the antibody. This technique was used in the photomicrograph in Figure 17.7.2 to identify the presence of a cell-surface antigen (shown as reddish-brown) in a sample of skin cells. This technique, called immunohistochemistry, is also commonly used to identify antigens in tissue samples from lymphoma patients.

Why would identifying cell-surface antigens be important in diagnosing and treating lymphoma? As you have learned, the immune system uses antigens present on the surface of cells or pathogens to distinguish between self and non-self, and to launch adaptive immune responses. Cells that become cancerous often change their cell-surface antigens. This is one way that the immune system can identify and destroy them. Also, different cell types in the body can sometimes be identified by the presence of specific cell-surface antigens. Knowing the types of cell-surface antigens present in a tissue sample can help physicians identify which cells are cancerous, and possibly the specific subtype of cancer. Knowing this information can be helpful in choosing more tailored and effective treatments.

One treatment for NHL is, in fact, the use of medications made from antibodies that bind to cell-surface antigens present on cells affected by the specific subtype of NHL. This is called immunotherapy. These drugs can directly bind to and kill the cancerous cells. For patients with DLBCL like Hakeem, immunotherapy is often used in conjunction with chemotherapy and radiation as a course of treatment. Although Hakeem has a difficult road ahead, he and his medical team are optimistic that — given the high success rate when DLBCL is caught and treated early — he may be cured. More research into how the immune system functions may lead to even better treatments for lymphoma — and other types of cancers — in the future.

Attributions

Figure 17.7.1

Cycling to Beat Blood Cancer by Blood Cancer UK (Formerly Bloodwise) on Flickr is used under a CC BY-NC-ND 2.0 (https://creativecommons.org/licenses/by-nc-nd/2.0/) license.

Figure 17.7.2

antigen stain by Ed Uthman from Houston, TX, USA on Wikimedia Commons is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0) license.

References

Hodgkin lymphoma statistics [online article]. (2020). Canadian Cancer Society. https://www.cancer.ca:443/en/cancer-information/cancer-type/hodgkin-lymphoma/statistics/?region=on

Non-Hodgkin lymphoma statistics [online article]. (2020). Canadian Cancer Society. https://www.cancer.ca:443/en/cancer-information/cancer-type/non-hodgkin-lymphoma/statistics/?region=on

TED-Ed. (2015, April 30). What is leukemia? - Danilo Allegra and Dania Puggioni. YouTube. https://www.youtube.com/watch?v=Z3B-AaqjyjE&feature=youtu.be

 

Created by CK-12 Foundation/Adapted by Christine Miller

This false-colour image (Figure 18.4.1) shows real human sperm. The tiny gametes are obviously greatly magnified in the picture, because they are actually the smallest of all human cells. In fact, human sperm cells are small, even when compared with sperm cells of other animals. Mice sperm are about twice the length of human sperm! Human sperm may be small in size, but in a normal, healthy man, huge numbers of them are usually released during each ejaculation. There may be hundreds of millions of sperm cells in a single teaspoon of semen. Producing sperm is one of the major functions of the male reproductive system.

A mature sperm cell has several structures that help it reach and penetrate an egg. These are labeled in the drawing of a sperm shown in Figure 18.4.2.

• The head is the part of the sperm that contains the nucleus — and not much else. The nucleus, in turn, contains tightly coiled DNA that is the male parent’s contribution to the genetic makeup of a zygote (if one forms). Each sperm is a haploid cell, containing half the chromosomal complement of a normal, diploid body cell.
• The front of the head is an area called the acrosome. The acrosome contains enzymes that help the sperm penetrate an ovum (if it reaches one).
• The midpiece is the part of the sperm between the head and the flagellum. The midpiece is packed with mitochondria that produce the energy needed to move the flagellum.
• The flagellum (also called the tail) can rotate like a propeller, allowing the sperm to “swim” through the female reproductive tract to reach an ovum if one is present.

The process of producing sperm is known as spermatogenesis. Spermatogenesis normally starts when a male reaches puberty, and it usually continues uninterrupted until death, although a decrease in sperm production generally occurs at older ages. A young, healthy male may produce hundreds of millions of sperm a day! Only about half of these, however, are likely to become viable, mature sperm.

Where Sperm Are Produced

Spermatogenesis occurs in the seminiferous tubules in the testes. Spermatogenesis requires high concentrations of testosterone. Testosterone is secreted by Leydig cells, which are adjacent to the seminiferous tubules in the testes.

Sperm production in the seminiferous tubules is very sensitive to temperature. This may be the most important reason the testes are located outside the body in the scrotum. The temperature inside the scrotum is generally about 2 degrees Celsius cooler than core body temperature. This lower temperature is optimal for spermatogenesis. The scrotum regulates its internal temperature as needed by contractions of the smooth muscles lining the scrotum. When the temperature inside the scrotum becomes too low, the scrotal muscles contract. The contraction of the muscles pulls the scrotum higher against the body, where the temperature is warmer. The opposite occurs when the temperature inside the scrotum becomes too high.

Events of Spermatogenesis

Figure 18.4.3 summarizes the main cellular events that occur in the process of spermatogenesis. The process begins with a diploid stem cell called a spermatogonium (plural, spermatogonia), and involves several cell divisions. The entire process takes at least ten weeks to complete, including maturation in the epididymis.

1. A spermatogonium undergoes mitosis to produce two diploid cells called primary spermatocytes. One of the primary spermatocytes goes on to produce sperm. The other replenishes the reserve of spermatogonia.
2. The primary spermatocyte undergoes meiosis I to produce two haploid daughter cells called secondary spermatocytes.
3. The secondary spermatocytes rapidly undergo meiosis II to produce a total of four haploid daughter cells called spermatids.
4. The spermatids begin to form a tail, and their DNA becomes highly condensed. Unnecessary cytoplasm and organelles are removed from the cells, and they form a head, midpiece, and flagellum. The resulting cells are sperm (spermatozoa).

As shown in Figure 18.4.4, the events of spermatogenesis begin near the wall of the seminiferous tubule — where spermatogonia are located — and continue inward toward the lumen of the tubule. Sertoli cells extend from the wall of the seminiferous tubule inward toward the lumen, so they are in contact with developing sperm at all stages of spermatogenesis. Sertoli cells play several roles in spermatogenesis:

• They secrete endocrine hormones that help regulate spermatogenesis.
• They secrete substances that initiate meiosis.
• They concentrate testosterone (from Leydig cells), which is needed at high levels to maintain spermatogenesis.
• They phagocytize the extra cytoplasm that is shed from developing sperm cells.
• They secrete testicular fluid that helps carry sperm into the epididymis.
• They maintain a blood-testis barrier, so immune system cells cannot reach and attack the sperm.

Maturation in the Epididymis

Although the sperm produced in the testes have tails, they are not yet motile (able to “swim”). The non-motile sperm are transported to the epididymis in testicular fluid that is secreted by Sertoli cells with the help of peristaltic contractions. In the epididymis, the sperm gain motility, so they are capable of swimming up the female genital tract and reaching an ovum. The mature sperm are stored in the epididymis until ejaculation occurs.

Sperm are released from the body during ejaculation, which typically occurs during orgasm. Hundreds of millions of mature sperm — contained within a small amount of thick, whitish fluid called semen — are propelled from the penis during a normal ejaculation.

How Ejaculation Occurs

Ejaculation occurs when peristalsis of the muscle layers of the vas deferens and other accessory structures propel sperm from the epididymes, where mature sperm are stored. The muscle contractions force the sperm through the vas deferens and the ejaculatory ducts, and then out of the penis through the urethra. Due to the peristaltic action of the muscles, the ejaculation occurs in a series of spurts.

The Role of Semen

As sperm travel through the ejaculatory ducts during ejaculation, they mix with secretions from the seminal vesicles, prostate gland, and bulbourethral glands to form semen (see Figure 18.4.5 ). The average amount of semen per ejaculate is about 3.7 mL, which is a little less than a teaspoonful. Most of this volume of semen consists of glandular secretions, with the hundreds of millions of sperm cells actually contributing relatively little to the total volume.

The secretions in semen are important for the survival and motility of sperm. They provide a medium through which sperm can swim. They also include sperm-sustaining substances, such as high concentrations of the sugar fructose, which is the main source of energy for sperm. In addition, semen contains many alkaline substances that help neutralize the acidic environment in the female vagina. This protects the DNA in sperm from being denatured by acid, and prolongs the life of sperm in the female reproductive tract.

Besides providing a way for sperm to leave the body, the main role of the penis in reproduction is intromission, or depositing sperm in the vagina of the female reproductive tract. Intromission depends on the ability of the penis to become stiff and erect, a state referred to as an erection. The human penis, unlike that of most other mammals, contains no erectile bone. Instead, in order to reach its erect state, it relies entirely on engorgement with blood of its columns of spongy tissue. During sexual arousal, the arteries that supply blood to the penis dilate, allowing more blood to fill the spongy tissue. The now-engorged spongy tissue presses against and constricts the veins that carry blood away from the penis. As a result, more blood enters than leaves the penis, until a constant erectile size is achieved.

In addition to sperm, the penis also transports urine out of the body. These two functions cannot occur simultaneously. During an erection, the sphincters that prevent urine from leaving the bladder are controlled by centres in the brain so they cannot relax and allow urine to enter the urethra.

The final major function of the male reproductive system is the production of the male sex hormone testosterone. In mature males, this occurs mainly in the testes. Testosterone production is under the control of luteinizing hormone (LH) from the pituitary gland. LH stimulates Leydig cells in the testes to secrete testosterone.

Testosterone is important for male sexual development at puberty. It stimulates maturation of the male reproductive organs, as well as the development of secondary male sex characteristics (such as facial hair). Testosterone is also needed in mature males for normal spermatogenesis to be maintained in the testes. Follicle stimulating hormone (FSH) from the pituitary gland is also needed for spermatogenesis to occur, in part because it helps Sertoli cells in the testes concentrate testosterone to high enough levels to maintain sperm production. Testosterone is also needed for proper functioning of the prostate gland. In addition, testosterone plays a role in erection, allowing sperm to be deposited within the female reproductive tract.

If you’re a man and you use a laptop computer on your lap for long periods of time, you may be decreasing your fertility. The reason? A laptop computer generates considerable heat, and its proximity to the scrotum during typical use results in a significant rise in temperature inside the scrotum. Spermatogenesis is very sensitive to high temperatures, so it may be adversely affected by laptop computer use. If you want to avoid the potentially fertility-depressing effect of laptop computer use, you might want to consider using your laptop computer on a table or other surface rather than on your lap — at least when you log on for long computer sessions. Other activities that raise scrotal temperature and have the potential to reduce spermatogenesis including soaking in hot tubs, wearing tight clothing, and biking. Although the effects of short-term scrotal heating on fertility seem to be temporary, years of such heat exposure may cause irreversible effects on sperm production.

Attributions

Figure 18.4.1

Sperm-20051108 by Gilberto Santa Rosa from Rio de Janeiro, Brazil on Wikimedia Commons is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0) license.

Figure 18.4.2

Sperm Anatomy by Christinelmiller on Wikimedia Commons is used under a  CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0) license.

Figure 18.4.3

Spermatogenesis by OpenStax College is used and adapted by Christine Miller under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 18.4.4

Testis-cross-section by CK-12 Foundation is used under a CC BY-NC 3.0 (https://creativecommons.org/licenses/by-nc/3.0/) license.

Figure 18.4.5

Human_semen_in_a_petri_dish by Digitalkil on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/en:public_domain).

Figure 18.4.6

Laptop by logan-weaver-b76PEyeIptQ-unsplash [photo] by LOGAN WEAVER on Unsplash is used under the Unsplash License (https://unsplash.com/license).

References

Betts, J. G., Young, K.A., Wise, J.A., Johnson, E., Poe, B., Kruse, D.H., Korol, O., Johnson, J.E., Womble, M., DeSaix, P. (2013, June 19). Figure 27.5 Spermatogenesis [digital image].  In Anatomy and Physiology (Section 27.1). OpenStax. https://openstax.org/books/anatomy-and-physiology/pages/27-1-anatomy-and-physiology-of-the-male-reproductive-system

Brainard, J/ CK-12 Foundation. (2016). Figure 4 Cross-section of a testis and seminiferous tubules [digital image]. In CK-12 College Human Biology (Section 20.4) [online Flexbook]. CK12.org. https://www.ck12.org/book/ck-12-college-human-biology/section/20.4/

Janux. (2015, January 10). Human physiology - Reproduction: spermatogenesis. YouTube. https://www.youtube.com/watch?v=krSMZDsjLuU&feature=youtu.be

Seeker. (2014, June 16). How you're destroying your sperm! YouTube. https://www.youtube.com/watch?v=gNHSTa0Yct4&feature=youtu.be

 

Created by CK-12 Foundation/Adapted by Christine Miller

The geometric design on the ancient stone carving in Figure 18.6.1 represents a powerful symbol of female fertility: the vagina. The symbol is called yoni in Hindu, and it reflects the value placed by Hindu culture on the ability of females to give birth. The vagina is one of several organs in the female reproductive system.

The female reproductive system is made up of internal and external organs that function to produce haploid female gametes called ova (or oocytes), secrete female sex hormones (such as estrogen), and carry and give birth to a fetus. The internal female reproductive organs include the vagina, uterus, oviducts, and ovaries. The external organs — collectively called the vulva — include the clitoris and labia.

The vagina is an elastic, muscular canal leading from its opening in the vulva to the neck of the uterus, called the cervix. It is about 7.5 cm (about 3 in) long at the front, and about 9 cm (3.5 in) long at the back. The vagina accommodates the penis and is the site where sperm are usually ejaculated during sexual intercourse. In the context of pregnancy and natural (vaginal) childbirth, the vagina is referred to as the birth canal. In addition, it channels the flow of menstrual blood from the uterus.

Structure of the Vagina

Muscles and ligaments support the vagina within the pelvic cavity. The vagina itself is made up of several layers of fibrous and muscular tissues and lined with mucous membranes. Folds in the mucosa provide the vagina with extra surface area so it can stretch in both length and width during intercourse or childbirth. The elasticity of the vagina and the extra mucosa allow it to stretch to many times its normal diameter in order to deliver a baby.

Bacteria and pH in the Vagina

A healthy vagina is home to many symbiotic bacteria that help prevent pathogens (such as yeast) from colonizing the vagina. The pH in the vagina is normally between 3.8 and 4.5, and this acidity also helps keep pathogenic microorganisms from colonizing it. The vagina constantly sheds its epithelium, so it is considered self-cleaning. As a consequence, there is no need for douching to clean it. Physicians actually discourage the practice, as it may upset the normal bacterial and pH balance in the vagina, although washing the vulva with a mild soap is good practice.

The uterus (commonly called the womb) is a pear-shaped, muscular organ that is about 7.6 cm (about 3 in) long. It is located above the vagina and behind the bladder in the centre of the pelvis. The position of the uterus in the pelvis is stabilized by several ligaments and bands of supportive tissue. The uterus is where a fetus develops during gestation, and the organ provides mechanical protection and support for the developing offspring. Contractions of the muscular wall of the uterus are responsible for pushing the fetus out of the uterus during childbirth.

Parts of the Uterus

As shown in Figure 18.6.2, the lower end of the uterus forms the cervix, which is also called the neck of the uterus. The cervix is about 2.5 cm (almost 1 in) long and protrudes downward into the vagina. A small canal runs the length of the cervix, connecting the uterine cavity with the lumen of the vagina. This allows semen deposited in the vagina to enter the uterus, and a baby to pass from the uterus into the vagina during birth. Glands in the cervix secrete mucus that varies in water content and thickness, so it can function either as a barrier to keep microorganisms out of the uterus during pregnancy, or as a transport medium to help sperm enter the uterus around the time of ovulation. The rest of the uterus above the cervix is called the body of the uterus. The upper end of the uterus is connected with the two oviducts.

Tissues of the Uterus

As indicated in Figure 18.6.3, the uterus consists of three tissue layers, called the endometrium, myometrium, and perimetrium.

• The endometrium is the innermost tissue layer of the uterus. It consists of epithelial tissue, including mucous membranes. This layer thickens during each menstrual cycle and, unless an egg is fertilized, sloughs off during the following menstrual period. If an ovum is fertilized, the thickened endometrium is maintained by hormones and provides nourishment to the embryo. As gestation progresses, the endometrium develops into the maternal portion of the placenta.
• The placenta is a temporary organ that consists of a mass of maternal and fetal blood vessels through which the mother’s and fetus’s blood exchange substances.
• The myometrium is the middle layer of the uterus. It consists mostly of a thick layer of smooth muscle tissue. Powerful contractions of the smooth muscle allow the uterus to contract and expel an infant during childbirth.
• The perimetrium is the outermost layer of the uterus. It covers the outer surface of the uterus. This layer actually consists of two layers of epithelium that secrete fluid into the space between them. The fluid allows for small movements of the uterus within the pelvis, without causing it to rub against other organs.

The oviducts (often referred to as Fallopian tubes) are two thin tubes that lie between the ovaries and the uterus. The oviducts are not attached to the ovaries, but their broad upper ends — called infundibula — lie very close to the ovaries. The infundibula also have fringe-like extensions called fimbriae that move in a waving motion to help guide eggs from the ovaries into the oviducts. The lower ends of the oviducts are attached to the upper part of the body of the uterus on either side of the body. They open into the uterus.

The oviducts are made up of multiple tissue layers. The innermost layer consists of mucosal epithelium. The epithelium is covered with cilia, which can move in a sweeping motion to help ova move through the tube from the ovary to the uterus. In between the ciliated cells of the epithelium are cells that secrete a fluid called tubular fluid. This fluid contains nutrients for sperm, ova, and zygotes. The secretions in tubular fluid also remove certain molecules from the plasma membrane of sperm so they are better able to penetrate an egg. Other layers of the oviducts consist of connective tissue and smooth muscle. Contractions of the smooth muscle allow peristalsis to help move eggs through the tubes.

Like the testes in males, the ovaries in females are gonads that produce gametes and secrete sex hormones. The gametes produced by the ovaries are called ova, or oocytes. The main sex hormone secreted by the ovaries is estrogen. The position of the paired ovaries relative to the other reproductive system organs is shown in Figure 18.6.4. Each ovary lies along one side of the uterus and is about 4 cm (a little more than 1.5 in) long. Fibrous ligaments attach one end of each ovary to its nearby oviduct and the other and to its side of the uterus. These ligaments keep the ovaries in place within the pelvis.

Ovarian Follicles

The ovary consists of two main layers, called the ovarian medulla (the inner layer) and the ovarian cortex (the outer layer). The ovary also contains blood and lymphatic vessels. The ovarian cortex consists primarily of the functional units of the ovaries, which are called ovarian follicles. The follicles are nests of epithelial cells, within each of which is an ovum. The photomicrograph in Figure 18.6.5 shows an ovarian follicle and the developing ovum inside it. If an ovum and follicle complete maturation, the follicle ruptures and the ovum is released from the ovary. This event is called ovulation.

Ova in the Ovaries

Whereas the male testes produce sperm continuously after puberty, the female ovary already contains all the ova it will ever produce by the time a female is born. At birth, a baby girl’s ovaries contain at least a million eggs, each of which is contained within a follicle. Only about 500 of these eggs will eventually mature and be ovulated. This process starts at puberty and typically continues at monthly intervals until menopause occurs around age 52. The remaining eggs never mature, and their number declines as the woman ages. By menopause, a woman’s reserve of eggs is nearly depleted, and ovulation no longer occurs.

The vulva is a general term for all of the external female reproductive organs. The vulva includes the clitoris, labia, and external openings for the urethra and vagina.

Labia

The labia (singular, labium) refer to the “lips” of the vulva, which are folds of tissue that contain and protect the other, more delicate structures of the vulva (as shown in Figure 18.6.6). There are two pairs of labia: the outer and larger labia majora, and the inner and smaller labia minora. The labia minora contain numerous sebaceous glands. These glands release secretions that help lubricate the labia and vulvar area.

Clitoris

The clitoris, is located at the front of the vulva where the labia minora meet. The visible portion of the clitoris is called the glans clitoris. It is roughly the size and shape of a pea. It is highly sensitive, because it contains many nerve endings. A hood of tissue called the clitoral hood (shown in Figure 18.6.5 above), or prepuce, normally covers and protects the clitoris. The clitoris is the homologue to the male penis, and they both contain spongy tissue.  Stimulation of the glans clitoris during sexual activity generally results in sexual arousal in females, and may lead to orgasm. The glans clitoris is the only part of the overall clitoris visible externally, but this spongy tissue extends down either side of the openings to the urethra and vagina, as seen in Figure 18.6.7.

Other Vulvar Structures

The area between the two labia minora is called the vestibule of the vulva. Both the urethra and vagina have openings to the outside of the body in the vestibule. As you can see in Figure 18.6.7 above, the urethral opening (or meatus) is located just in front of, and is much smaller than, the vaginal opening. Both openings are protected by the labia. Two glands — called Bartholin’s glands — open on either side of the vaginal opening. These glands secrete mucus and a vaginal and vulvar lubricant.

The breasts are not directly involved in reproduction, but because they contain mammary glands, they can provide nourishment to an infant after birth. The breasts overlay major muscles in the chest from which they project outward in a conical shape. The two main types of tissues in the breast are adipose (fat) tissue and glandular tissue that produces milk. As shown in Figure 18.6.8, each mature breast contains many lobules, where milk is produced and stored during pregnancy. During breastfeeding (or lactation), the milk drains into ducts and sacs, which in turn converge at the nipple. Milk exits the breast through the nipple in response to the suckling action of an infant and is regulated by a positive feedback loop. The nipple is surrounded by a more darkly pigmented area called the areola. The areola contains glands that secrete an oily fluid, which lubricates and protects the nipple during breastfeeding.

Betts, J. G., Young, K.A., Wise, J.A., Johnson, E., Poe, B., Kruse, D.H., Korol, O., Johnson, J.E., Womble, M., DeSaix, P. (2013, June 19). Figure 27.10 The vulva [digital image].  In Anatomy and Physiology (Section 27.2). OpenStax. https://openstax.org/books/anatomy-and-physiology/pages/27-2-anatomy-and-physiology-of-the-female-reproductive-system

Janux. (2015, January 10). Human physiology - Functional anatomy of the female reproductive system. YouTube. https://www.youtube.com/watch?v=9rs2gNchQig&feature=youtu.be

TED. (2019, March 22). The uncomplicated truth about women's sexuality | Sarah Barmak. YouTube.  https://www.youtube.com/watch?v=SkB4gG8ke7Q&feature=youtu.be

Teixeira, J., Rueda, B.R., and Pru, J.K. (September 30, 2008). Figure 1 Uterine anatomy. In Uterine Stem Cells (StemBook, ed.). The Stem Cell Research Community, StemBook, doi/10.3824/stembook.1.16.1, http://www.stembook.org

Created by CK-12 Foundation/Adapted by Christine Miller

The banner in Figure 18.8.1 was carried in a 2014 march in Uganda as part of the celebration of Menstrual Hygiene Day. Menstrual Hygiene Day is an awareness day on May 28 of each year that aims to raise awareness worldwide about menstruation and menstrual hygiene. Maintaining good menstrual hygiene is difficult in developing countries like Uganda because of taboos on discussing menstruation and lack of availability of menstrual hygiene products. Poor menstrual hygiene, in turn, can lead to embarrassment, degradation, and reproductive health problems in females. May 28 was chosen as Menstrual Hygiene Day because of its symbolism. May is the fifth month of the year, and most women average five days of menstrual bleeding each month. The 28th day was chosen because the menstrual cycle averages about 28 days.

The menstrual cycle refers to natural changes that occur in the female reproductive system each month during the reproductive years. The cycle is necessary for the production of ova and the preparation of the uterus for pregnancy. It involves changes in both the ovaries and the uterus, and is controlled by pituitary and ovarian hormones. Day 1 of the cycle is the first day of the menstrual period, when bleeding from the uterus begins as the built-up endometrium lining the uterus is shed. The endometrium builds up again during the remainder of the cycle, only to be shed again during the beginning of the next cycle if pregnancy does not occur. In the ovaries, the menstrual cycle includes the development of a follicle, ovulation of a secondary oocyte, and then degeneration of the follicle if pregnancy does not occur. Both uterine and ovarian changes during the menstrual cycle are generally divided into three phases, although the phases are not the same in the two organs.

Menarche and Menopause

The female reproductive years are delineated by the start and stop of the menstrual cycle. The first menstrual period usually occurs around 12 or 13 years of age, an event that is known as menarche. There is considerable variation among individuals in the age at menarche. It may occasionally occur as early as eight years of age or as late as 16 years of age and still be considered normal. The average age is generally later in the developing world, and earlier in the developed world. This variation is thought to be largely attributable to nutritional differences.

The cessation of menstrual cycles at the end of a woman’s reproductive years is termed menopause. The average age of menopause is 52 years, but it may occur normally at any age between about 45 and 55 years of age. The age of menopause varies due to a variety of biological and environmental factors. It may occur earlier as a result of certain illnesses or medical treatments.

Variation in the Menstrual Cycle

The length of the menstrual cycle — as well as its phases — may vary considerably, not only among different women, but also from month to month for a given woman. The average length of time between the first day of one menstrual period and the first day of the next menstrual period is 28 days, but it may range from 21 days to 45 days. Cycles are considered regular when a woman’s longest and shortest cycles differ by less than eight days. The menstrual period itself is usually about five days long, but it may vary in length from about two days to seven days.

The events of the menstrual cycle that take place in the ovaries make up the ovarian cycle. It consists of changes that occur in the follicles of one of the ovaries. The ovarian cycle is divided into the following three phases: follicular phase, ovulation, and luteal phase. These phases are illustrated in Figure 18.8.2.

Follicular Phase

The follicular phase is the first phase of the ovarian cycle. It generally lasts about 12 to 14 days for a 28-day menstrual cycle. During this phase, several ovarian follicles are stimulated to begin maturing, but usually only one — called the Graafian follicle — matures completely so it is ready to release an egg. The other maturing follicles stop growing and disintegrate. Follicular development occurs because of a rise in the blood level of follicle stimulating hormone (FSH), which is secreted by the pituitary gland. The maturing follicle releases estrogen, the level of which rises throughout the follicular phase. You can see these and other changes in hormone levels that occur during the menstrual cycle in the following chart.

Ovulation

Ovulation is the second phase of the ovarian cycle. It usually occurs around day 14 of a 28-day menstrual cycle. During this phase, the Graafian follicle ruptures and releases its ovum. Ovulation is stimulated by a sudden rise in the blood level of luteinizing hormone (LH) from the pituitary gland. This is called the LH surge. You can see the LH surge in the top hormone graph in Figure 18.8.3. The LH surge generally starts around day 12 of the cycle and lasts for a day or two. The surge in LH is triggered by a continued rise in estrogen from the maturing follicle in the ovary. During the follicular phase, the rising estrogen level actually suppresses LH secretion by the pituitary gland. However, by the time the follicular phase is nearing its end, the level of estrogen reaches a threshold level above which this effect is reversed, and estrogen stimulates the release of a large amount of LH. The surge in LH matures the ovum and weakens the wall of the follicle, causing the fully developed follicle to release its secondary oocyte.

Luteal Phase

The luteal phase is the third and final phase of the ovarian cycle. It typically lasts about 14 days in a 28-day menstrual cycle. At the beginning of the luteal phase, FSH and LH cause the Graafian follicle that ovulated the egg to transform into a structure called a corpus luteum. The corpus luteum secretes progesterone, which in turn suppresses FSH and LH production by the pituitary gland and stimulates the continued buildup of the endometrium in the uterus. How this phase ends depends on whether or not the ovum has been fertilized.

• If fertilization has not occurred, the falling levels of FSH and LH during the luteal phase cause the corpus luteum to atrophy, so its production of progesterone declines. Without a high level of progesterone to maintain it, the endometrium starts to break down. By the end of the luteal phase, the endometrium can no longer be maintained, and the next menstrual cycle begins with the shedding of the endometrium (menses).
• If fertilization has occurred so a zygote forms and then divides to become a blastocyst, the outer layer of the blastocyst produces a hormone called human chorionic gonadotropin (HCG). This hormone is very similar to LH and preserves the corpus luteum. The corpus luteum can then continue to secrete progesterone to maintain the new pregnancy.

The events of the menstrual cycle that take place in the uterus make up the uterine cycle. This cycle consists of changes that occur mainly in the endometrium, which is the layer of tissue that lines the uterus. The uterine cycle is divided into the following three phases: menstruation, proliferative phase, and secretory phase. These phases are illustrated in Figure 18.8.4.

Menstruation

Menstruation (also called menstrual period or menses) is the first phase of the uterine cycle. It occurs if fertilization has not taken place during the preceding menstrual cycle. During menstruation, the endometrium of the uterus, which has built up during the preceding cycle, degenerates and is shed from the uterus, flowing through an opening in the cervix, and out through the external opening of the vagina. The average loss of blood during menstruation is about 35 mL (about 1 oz or 2 tablespoons). The flow of blood is often accompanied by uterine cramps, which may be severe in some women.

Proliferative Phase

The proliferative phase is the second phase of the uterine cycle. During this phase, estrogen secreted by cells of the maturing ovarian follicle causes the lining of the uterus to grow, or proliferate. Estrogen also stimulates the cervix of the uterus to secrete larger amounts of thinner mucus that can help sperm swim through the cervix and into the uterus, making fertilization more likely.

Secretory Phase

The secretory phase is the third and final phase of the uterine cycle. During this phase, progesterone produced by the corpus luteum in the ovary stimulates further changes in the endometrium so it is more receptive to implantation of a blastocyst. For example, progesterone increases blood flow to the uterus and promotes uterine secretions. It also decreases the contractility of smooth muscle tissue in the uterine wall.

 

Bringing it All Together

It is important to note that the pituitary gland, the ovaries and the uterus are all responsible for parts of the ovarian and uterine cycles.  The pituitary hormones, LH and FSH affect the ovarian cycle and its hormones.  The ovarian hormones, estrogen and progesterone affect the uterine cycle and also feedback on the pituitary gland.  Look at Figure 18.8.5 and look at what is happening on different days of the cycle in each of the sets of hormones, the ovarian cycle and the uterine cycle.

 

Attributions

Figure 18.8.1

WaterforPeople_Uganda by WaterforPeople_Uganda on Wikimedia Commons is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0) license.

Figure 18.8.2

Ovarian Cycle by CNX OpenStax on Wikimedia Commons is used and adapted under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0) license.

Figure 18.8.3

Figure_43_04_04 by CNX OpenStax on Wikimedia Commons is used under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0) license. (Original: modification of work by Mikael Häggström)

Figure 18.8.4

Ovarian and menstrual cycle by OpenStax College on Wikimedia Commons is used under a  CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 18.8.5

1000px-MenstrualCycle2_en.svg by Isometrik on Wikimedia Common is used under a CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) license.

References

Betts, J. G., Young, K.A., Wise, J.A., Johnson, E., Poe, B., Kruse, D.H., Korol, O., Johnson, J.E., Womble, M., DeSaix, P. (2013, June 19). Figure 27.15 Hormone levels in ovarian and menstrual cycles [digital image].  In Anatomy and Physiology (Section 27.2). OpenStax. https://openstax.org/books/anatomy-and-physiology/pages/27-2-anatomy-and-physiology-of-the-female-reproductive-system

National Geographic. (2007, May 31). Girl's rite of passage | National Geographic. YouTube. https://www.youtube.com/watch?v=5B3Abpv0ysM&feature=youtu.be

OpenStax. (2016, May 27) Figure 4 Rising and falling hormone levels result in progression of the ovarian and menstrual cycles [digital image]. In Open Stax, Biology (Section 43.4). OpenStax CNX. https://cnx.org/contents/GFy_h8cu@10.53:Ha3dnFEx@6/Hormonal-Control-of-Human-Reproduction

TED-Ed. (2015, October 19). Why do women have periods? YouTube.  https://www.youtube.com/watch?v=cjbgZwgdY7Q&feature=youtu.be

A synovial joint in which an oval-shaped process of one bone fits into a roughly elliptical cavity of the other, allowing movement in two planes.

Created by CK-12 Foundation/Adapted by Christine Miller

Figure 18.10.1 Families all have something in common.

What do all these families (Figure 18.10.1) have in common?  They were born!  Every person on this planet was conceived, carried in utero and then born.  While families come in all shapes, sizes and styles, we all came into existence in the same way.  Virtually all human societies past and present — value having children. Indeed, for many people, parenthood is an important life goal. Unfortunately, some people are unable to achieve that goal because of infertility.

Infertility is the inability of a sexually mature adult to reproduce by natural means. For scientific and medical purposes, infertility is generally defined as the failure to achieve a successful pregnancy after at least one year of regular, unprotected sexual intercourse. Infertility may be primary or secondary. Primary infertility applies to cases in which an individual has never achieved a successful pregnancy. Secondary infertility applies to cases in which an individual has had at least one successful pregnancy, but fails to achieve another after trying for at least a year. Infertility is a common problem. The government of Canada reported that in 2019, 16% of Canadian couples experience infertility, a number which has doubled since the 1980s. If you look around at the couples you know, that means that almost 1 in 6 of them are having issues with fertility.

Pregnancy is the result of a multi-step process. In order for a normal pregnancy to occur, a woman must release an ovum from one of her ovaries, the ovum must go through an oviduct, a man’s sperm must fertilize the ovum as it passes through the oviduct, and then the resulting zygote must implant in the uterus. If there is a problem with any of these steps, infertility can result.

A couple’s infertility may be due to a problem with either the male or the female partner. As shown in the circle graph below (Figure 18.10.2), about 40% of infertility cases are due to female infertility, and about 30% are due to male infertility. The remaining 30% of cases are due to a combination of male and female problems or unknown causes.

Causes of Male Infertility

Male infertility occurs when there are no, or too few, sperm, or when the sperm are not healthy and motile and cannot travel through the female reproductive tract to fertilize an egg. A common cause of inadequate numbers or motility of sperm is varicocele, which is enlargement of blood vessels in the scrotum. This may raise the temperature of the testes and adversely affect sperm production. In other cases, there is no problem with the sperm, but there is a blockage in the male reproductive tract that prevents the sperm from being ejaculated.

Factors that increase a man’s risk of infertility include heavy alcohol use, drug abuse, cigarette smoking, exposure to environmental toxins (such as pesticides or lead), certain medications, serious diseases (such as kidney disease), and radiation or chemotherapy for cancer. Another risk factor is advancing age. Male fertility normally peaks in the mid-twenties and gradually declines after about age 40, although it may never actually drop to zero.

Causes of Female Infertility

Female infertility generally occurs due to one of two problems: failure to produce viable ova by the ovaries, or structural problems in the oviducts or uterus. The most common cause of female infertility is a problem with ovulation. Without ovulation, there are no ova to be fertilized. Anovulatory cycles (menstrual cycles in which ovulation does not occur) may be associated with no or irregular menstrual periods, but even regular menstrual periods may be anovulatory for a variety of reasons. The most common cause of anovulatory cycles is polycystic ovary syndrome (PCOS), which causes hormone imbalances that can interfere with normal ovulation. Another relatively common cause of anovulation is primary ovarian insufficiency. In this condition, the ovaries stop working normally and producing viable eggs at a relatively early age, generally before the age of 40.

Structural problems with the oviducts or uterus are less common causes of female infertility. The oviducts may be blocked as a result of endometriosis. Another possible cause is pelvic inflammatory disease, which occurs when sexually transmitted infections spread to the oviducts or other female reproductive organs (see Figure 18.10.3). The infection may lead to scarring and blockage of the oviducts. If an ovum is produced and the oviducts are functioning — and a woman has a condition such as uterine fibroids — implantation in the uterus may not be possible. Uterine fibroids are non-cancerous clumps of tissue and muscle that form on the walls of the uterus.

Factors that increase a woman’s risk of infertility include tobacco smoking, excessive use of alcohol, stress, poor diet, strenuous athletic training, and being overweight or underweight. Advanced age is even more problematic for females than males. Female fertility normally peaks in the mid-twenties, and continuously declines after age 30 and until menopause around the age of 52, after which the ovary no longer releases eggs. About 1/3 of couples in which the woman is over age 35 have fertility problems. In older women, more cycles are likely to be anovulatory, and the eggs may not be as healthy.

Diagnosing Causes of Infertility

Diagnosing the cause(s) of a couple’s infertility often requires testing both the man and the woman for potential problems. In men, the semen is likely to be examined for the number, shape, and motility of sperm. If problems are found with sperm, further studies are likely to be done, such as medical imaging to look for structural problems with the testes or ducts.

In women, the first step is most often determining whether ovulation is occurring. This can be done at home by carefully monitoring body temperature (it rises slightly around the time of ovulation) or using a home ovulation test kit, which is available over the counter at most drugstores. Whether or not ovulation is occurring can also be detected with blood tests or ultrasound imaging of the ovaries. If ovulation is occurring normally, then the next step may be an X-ray of the oviducts and uterus to see if there are any blockages or other structural problems. Another approach to examining the female reproductive tract for potential problems is laparoscopy. In this surgical procedure, a tiny camera is inserted into the woman’s abdomen through a small incision. This allows the doctor to directly inspect the reproductive organs.

Infertility often can be treated successfully. The type of treatment depends on the cause of infertility.

Treating Male Infertility

Medical problems that interfere with sperm production may be treated with medications or other interventions that may lead to the resumption of normal sperm production. If, for example, an infection is interfering with sperm production, then antibiotics that clear up the infection may resolve the problem. If there is a blockage in the male reproductive tract that prevents the ejaculation of sperm, surgery may be able to remove the blockage. Alternatively, the man’s sperm may be removed from his body and then used for artificial insemination of his partner. In this procedure, the sperm are injected into the woman’s reproductive tract.

Treating Female Infertility

In females, it may be possible to correct blocked Fallopian tubes or uterine fibroids with surgery. Ovulation problems, on the other hand, are usually treated with hormones that act either on the pituitary gland or on the ovaries. Hormonal treatments that stimulate ovulation often result in more than one egg being ovulated at a time, thus increasing the chances of a woman having twins, triplets, or even higher multiple births. Multiple fetuses are at greater risk of being born too early or having health and developmental problems. The mother is also at greater risk of complications arising during pregnancy. Therefore, the possibility of multiple fetuses should be weighed in making a decision about this type of infertility treatment.

Assisted Reproductive Technology

Some cases of infertility are treated with assisted reproductive technology (ART). This is a collection of medical procedures in which ova are removed from the woman’s body and sperm are taken from the man’s body to be manipulated in ways that increase the chances of fertilization occurring. The eggs and sperm may be injected into one of the woman’s oviducts for fertilization to take place in vivo (in the body). More commonly, however, the eggs and sperm are mixed together outside the body so fertilization takes place in vitro (in a test tube or dish in a lab). The latter approach is illustrated in Figure 18.10.4. With in vitro fertilization, the fertilized eggs may be allowed to develop into embryos before being placed in the woman’s uterus.

ART has about a 40% chance of leading to a live birth in women under the age of 35, but only about a 20%t chance of success in women over the age of 35. Some studies have found a higher-than-average risk of birth defects in children produced by ART procedures, but this may be due to the generally higher ages of the parent — not the technologies used.

Other Approaches

Other approaches for certain causes of infertility include the use of a surrogate mother, a gestational carrier, or sperm donation.

• A surrogate mother is a woman who agrees to become pregnant using the man’s sperm and her own egg. The child, who will be the biological offspring of the surrogate and the male partner, is given up at birth for adoption by the couple. Surrogacy might be selected by women with no eggs or unhealthy eggs. A woman who carries a mutant gene for a serious genetic disorder might choose this option to ensure that the defective gene is not passed on to the offspring.
• A gestational carrier is a woman who agrees to receive a transplanted embryo from a couple and carry it to term. The child, who will be the biological offspring of the couple, is given to the parents at birth. A gestational carrier might be used by women who have normal ovulation but no uterus, or who cannot safely carry a fetus to term because of a serious health problem (such as kidney disease or cancer).
• Sperm donation is the use of sperm from a fertile man (generally through artificial insemination) for cases in which the male partner in a couple is infertile, or in which a woman seeks to become pregnant without a male partner. A lesbian couple may use donated sperm to enable one of them to become pregnant and have a child. Sperm can be obtained from a sperm bank, which buys and stores sperm for artificial insemination, or a male friend or other individual may donate sperm to a specific woman.

For people who have a strong desire for children of their own, infertility may lead to deep disappointment and depression. Individuals who are infertile may even feel biologically inadequate. Partners in infertile couples may argue and feel resentment toward each other, and married couples may get divorced because of infertility. Infertility treatments — especially ART procedures — are generally time-consuming and expensive. The high cost of the treatments can put them out of financial reach of many couples.

Ethical Concerns

Some people question whether the allocation of medical resources to infertility treatments is justified, and whether the resources could be better used in other ways. The status of embryos that are created in vitro and then not used for a pregnancy is another source of debate. Some people oppose their destruction on religious grounds, and couples may sometimes argue about what should be done with their extra embryos. Ethical issues are also raised by procedures that increase the chances of multiple births, because of the medical and developmental risks associated with multiple births.

Infertility in Developing Countries

Infertility is an under-appreciated problem in the poorer nations of the world, because of assumptions about overpopulation problems and high birth rates in developing countries. In fact, infertility is at least as great a problem in developing as in developed countries. High rates of health problems and inadequate health care in the poorer nations increase the risk of infertility. At the same time, infertility treatments are usually not available — or are far too expensive — for the vast majority of people who may need them. In addition, in many developing countries, the production of children is highly valued. Children may be needed for family income generation and economic security of the elderly. It is not uncommon for infertility to lead to social stigmatization, psychological problems, and abandonment by spouses.

Attributions

Figure 18.10.1

• Gay Pride Parade NYC 2013 - Happy Family by Bob Jagendorf on Flickr is used under a CC BY-NC 2.0 (https://creativecommons.org/licenses/by-nc/2.0/) license.
• #beaches #summer #family #blue #water by Jove Duero on Unsplash is used under the Unsplash License (https://unsplash.com/license).
• Photograph of five men near outdoor by Dollar Gill on Unsplash is used under the Unsplash License (https://unsplash.com/license). 
• Família by Laercio Cavalcanti on Unsplash is used under the Unsplash License (https://unsplash.com/license). 
• Happiness 🙂 by Ashwini Chaudhary on Unsplash is used under the Unsplash License (https://unsplash.com/license). 

Figure 18.10.2

Causes of infertility in Canada by Christine Miller is in the Public Domain (https://creativecommons.org/publicdomain/mark/1.0/).

Figure 18.10.3

1024px-Blausen_0719_PelvicInflammatoryDisease by BruceBlaus on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license. 

Figure 18.10.4

1024px-Blausen_0060_AssistedReproductiveTechnology by BruceBlaus on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license. 

References

Blausen.com Staff. (2014). Medical gallery of Blausen Medical 2014. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436.

David Pakman Show. (2015, September 1). Smoking marijuana may lower sperm count by 33%. YouTube. https://www.youtube.com/watch?v=iqA8uAjvEdM

Fertility Specialist Sydney. (2014, April 11). ivf embryo developing over 5 days by fertility Dr Raewyn Teirney. YouTube. https://www.youtube.com/watch?v=V6-v4eF9dyA&t=5s

Public Health Agency of Canada. (2019, May 28). Fertility. Government of Canada. https://www.canada.ca/en/public-health/services/fertility/fertility.html

TED-Ed. (2015, May 7). How in vitro fertilization (IVF) works - Nassim Assefi and Brian A. Levine.  YouTube. https://www.youtube.com/watch?v=P27waC05Hdk&t=4s

TEDx Talks. (2014, June 26). A journey through infertility -- over terror's edge | Camille Preston | TEDxBeaconStreet. YouTube. https://www.youtube.com/watch?v=6BBmMtVfZ4Y&t=2s

TEDx Talks. (2016, November 15). Homosexuality: It's about survival - not sex | James O'Keefe | TEDxTallaght. YouTube. https://www.youtube.com/watch?v=4Khn_z9FPmU&t=1s

A rigid organ that constitutes part of the vertebrate skeleton in animals.