Created by: CK-12/Adapted by Christine Miller

The 25-metre long sculpture shown in Figure 4.6.1 is a recognition of the beauty of one of the metabolic functions that takes place in the cells in your body.  This artwork brings to life an important structure in living cells: the ribosome, the cell structure where proteins are synthesized. The slender silver strand is the messenger RNA(mRNA) bringing the code for a protein out into the cytoplasm.  The purple and green structures are ribosomal subunits (which together form a single ribosome), which can "read" the code on the mRNA and direct the bonding of the correct sequence of amino acids to create a protein.  All living cells — whether they are prokaryotic or eukaryotic — contain ribosomes, but only eukaryotic cells also contain a nucleus and several other types of organelles.

An organelle is a structure within the cytoplasm of a eukaryotic cell that is enclosed within a membrane and performs a specific job. Organelles are involved in many vital cell functions. Organelles in animal cells include the nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus, vesicles, and vacuoles. Ribosomes are not enclosed within a membrane, but they are still commonly referred to as organelles in eukaryotic cells.

The nucleus is the largest organelle in a eukaryotic cell, and it's considered the cell’s control center. It contains most of the cell’s DNA(which makes up chromosomes), and it is encoded with the genetic instructions for making proteins. The function of the nucleus is to regulate gene expression, including controlling which proteins the cell makes. In addition to DNA, the nucleus contains a thick liquid called nucleoplasm, which is similar in composition to the cytosol found in the cytoplasm outside the nucleus. Most eukaryotic cells contain just a single nucleus, but some types of cells (such as red blood cells) contain no nucleus and a few other types of cells (such as muscle cells) contain multiple nuclei.

As you can see in the model pictured in Figure 4.6.2, the membrane enclosing the nucleus is called the nuclear envelope. This is actually a double membrane that encloses the entire organelle and isolates its contents from the cellular cytoplasm. Tiny holes called nuclear pores allow large molecules to pass through the nuclear envelope, with the help of special proteins. Large proteins and RNA molecules must be able to pass through the nuclear envelope so proteins can be synthesized in the cytoplasm and the genetic material can be maintained inside the nucleus. The nucleolus shown in the model below is mainly involved in the assembly of ribosomes. After being produced in the nucleolus, ribosomes are exported to the cytoplasm, where they are involved in the synthesis of proteins.

The mitochondrion (plural, mitochondria) is an organelle that makes energy available to the cell. This is why mitochondria are sometimes referred to as the "power plants of the cell." They use energy from organic compounds (such as glucose) to make molecules of ATP (adenosine triphosphate), an energy-carrying molecule that is used almost universally inside cells for energy.

Mitochondria (as in the Figure 4.6.3 diagram) have a complex structure including an inner and out membrane.  In addition, mitochondria have their own DNA, ribosomes, and a version of cytoplasm, called matrix.  Does this sound similar to the requirements to be considered a cell?  That's because they are!

Scientists think that mitochondria were once free-living organisms because they contain their own DNA. They theorize that ancient prokaryotes infected (or were engulfed by) larger prokaryotic cells, and the two organisms evolved a symbiotic relationship that benefited both of them. The larger cells provided the smaller prokaryotes with a place to live. In return, the larger cells got extra energy from the smaller prokaryotes. Eventually, the smaller prokaryotes became permanent guests of the larger cells, as organelles inside them. This theory is called endosymbiotic theory, and it is widely accepted by biologists today. (See the video in section 4.3 to learn all about endosymbiotic theory.)

The endoplasmic reticulum (ER) is an organelle that helps make and transport proteins and lipids. There are two types of endoplasmic reticulum: rough endoplasmic reticulum (rER) and smooth endoplasmic reticulum (sER). Both types are shown in Figure 4.6.4.

• rER looks rough because it is studded with ribosomes. It provides a framework for the ribosomes, which make proteins. Bits of its membrane pinch off to form tiny sacs called vesicles, which carry proteins away from the ER.
• sER looks smooth because it does not have ribosomes. sER makes lipids, stores substances, and plays other roles.

The Golgi apparatus (shown in the Figure 4.6.4 diagram) is a large organelle that processes proteins and prepares them for use both inside and outside the cell. You can see the Golgi apparatus in the figure above. The Golgi apparatus is something like a post office. It receives items (proteins from the ER), then packages and labels them before sending them on to their destinations (to different parts of the cell or to the cell membrane for transport out of the cell). The Golgi apparatus is also involved in the transport of lipids around the cell.

Both vesicles and vacuoles are sac-like organelles made of phospholipid bilayer that store and transport materials in the cell. Vesicles are much smaller than vacuoles and have a variety of functions. The vesicles that pinch off from the membranes of the ER and Golgi apparatus store and transport protein and lipid molecules. You can see an example of this type of transport vesicle in the Figure 4.6.4. Some vesicles are used as chambers for biochemical reactions.

There are some vesicles which are specialized to carry out specific functions.  Lysosomes, which use enzymes to break down foreign matter and dead cells, have a double membrane to make sure their contents don't leak into the rest of the cell.  Peroxisomes are another type of specialized vesicle with the main function of breaking down fatty acids and some toxins. 

Centrioles are organelles involved in cell division. The function of centrioles is to help organize the chromosomes before cell division occurs so that each daughter cell has the correct number of chromosomes after the cell divides. Centrioles are found only in animal cells, and are located near the nucleus. Each centriole is made mainly of a protein named tubulin. The centriole is cylindrical in shape and consists of many microtubules, as shown in the model pictured in Figure 4.6.5.

Ribosomes are small structures where proteins are made. Although they are not enclosed within a membrane, they are frequently considered organelles. Each ribosome is formed of two subunits, like the ones pictured at the beginning of this section (Figure 4.6.1) and in  Figure 4.6.6. Both subunits consist of proteins and RNA. mRNA from the nucleus carries the genetic code, copied from DNA, which remains in the nucleus. At the ribosome, the genetic code in mRNA is used to assemble and join together amino acids to make proteins. Ribosomes can be found alone or in groups within the cytoplasm, as well as on the rER.

Attributes

Figure 4.6.1 

Ribosomes at Work by Pedrik on Flickr is used under a CC BY-NC-SA 2.0 (https://creativecommons.org/licenses/by-nc-sa/2.0/) license.

Figure 4.6.2

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

Figure 4.6.3 

Mitochondrion_structure.svg by Kelvinsong; modified by Sowlos on Wikimedia Commons is used and adapted by Christine Miller under a CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) license.

Figure 4.6.4

Endomembrane_system_diagram_en.svg by Mariana Ruiz [LadyofHats] on Wikimedia Commons is released into the public domain (https://en.wikipedia.org/wiki/Public_domain).

Figure 4.6.5

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

Figure 4.6.6

Ribosome_shape by Vossman on Wikimedia Commons is used and adapted by Christine Miller under a CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) license.

References

Blausen.com staff. (2014). Nucleus - Medical gallery of Blausen Medical 2014. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. https://en.wikiversity.org/wiki/WikiJournal_of_Medicine/Medical_gallery_of_Blausen_Medical_2014

Blausen.com staff (2014). Centrioles - Medical gallery of Blausen Medical 2014. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436.https://en.wikiversity.org/wiki/WikiJournal_of_Medicine/Medical_gallery_of_Blausen_Medical_2014

Nucleus Medical Media. (2015, March 18). Biology: Cell structure I Nucleus Medical Media. YouTube. https://www.youtube.com/watch?v=URUJD5NEXC8&feature=youtu.be

TED. (2007, July 24). David Bolinsky: Visualizing the wonder of a living cell. YouTube. https://www.youtube.com/watch?v=Id2rZS59xSE&feature=youtu.be

 

 

Created by CK-12 Foundation/Adapted by Christine Miller

Did you ever hear of a person looking at something or someone with a “jaundiced eye”? It means to take a negative view, such as envy, maliciousness, or ill will. The expression may be based on the antiquated idea that liver bile is associated with such negative emotions as these, as well as the fact that excessive liver bile causes jaundice, or yellowing of the eyes and skin. Jaundice is likely a sign of a liver disorder or blockage of the duct that carries bile away from the liver. Bile contains waste products, making the liver an organ of excretion. Bile has an important role in digestion, which makes the liver an accessory organ of digestion, too.

Accessory organs of digestion are organs that secrete substances needed for the chemical digestion of food, but through which food does not actually pass as it is digested. Besides the liver, the major accessory organs of digestion are the gallbladder and pancreas. These organs secrete or store substances that are needed for digestion in the first part of the small intestine — the duodenum — where most chemical digestion takes place. You can see the three organs and their locations in Figure 15.6.2.

Liver

The liver is a vital organ located in the upper right part of the abdomen. It lies just below the diaphragm, to the right of the stomach. The liver plays an important role in digestion by secreting bile, but the liver has a wide range of additional functions unrelated to digestion. In fact, some estimates put the number of functions of the liver at about 500! A few of them are described below.

Structure of the Liver

The liver is a reddish brown, wedge-shaped structure. In adults, the liver normally weighs about 1.5 kg (about 3.3 lb). It is both the heaviest internal organ and the largest gland in the human body. The liver is divided into four lobes of unequal size and shape. Each lobe, in turn, is made up of lobules, which are the functional units of the liver. Each lobule consists of millions of liver cells, called hepatic cells (or hepatocytes). They are the basic metabolic cells that carry out the various functions of the liver.

As shown in Figure 15.6.3, the liver is connected to two large blood vessels: the hepatic artery and the portal vein. The hepatic artery carries oxygen-rich blood from the aorta, whereas the portal vein carries blood that is rich in digested nutrients from the GI tract and wastes filtered from the blood by the spleen. The blood vessels subdivide into smaller arteries and capillaries, which lead into the liver lobules. The nutrients from the GI tract are used to build many vital biochemical compounds, and the wastes from the spleen are degraded and excreted.

Functions of the Liver

The main digestive function of the liver is the production of bile. Bile is a yellowish alkaline liquid that consists of water, electrolytes, bile salts, and cholesterol, among other substances, many of which are waste products. Some of the components of bile are synthesized by hepatocytes. The rest are extracted from the blood.

As shown in Figure 15.6.4, bile is secreted into small ducts that join together to form larger ducts, with just one large duct carrying bile out of the liver. If bile is needed to digest a meal, it goes directly to the duodenum through the common bile duct. In the duodenum, the bile neutralizes acidic chyme from the stomach and emulsifies fat globules into smaller particles (called micelles) that are easier to digest chemically by the enzyme lipase. Bile also aids with the absorption of vitamin K. Bile that is secreted when digestion is not taking place goes to the gallbladder for storage until the next meal. In either case, the bile enters the duodenum through the common bile duct.

Besides its roles in digestion, the liver has many other vital functions:

• The liver synthesizes glycogen from glucose and stores the glycogen as required to help regulate blood sugar levels. It also breaks down the stored glycogen to glucose and releases it back into the blood as needed.
• The liver stores many substances in addition to glycogen, including vitamins A, D, B12, and K. It also stores the minerals iron and copper.
• The liver synthesizes numerous proteins and many of the amino acids needed to make them. These proteins have a wide range of functions. They include fibrinogen, which is needed for blood clotting; insulin-like growth factor (IGF-1), which is important for childhood growth; and albumen, which is the most abundant protein in blood serum and functions to transport fatty acids and steroid hormones in the blood.
• The liver synthesizes many important lipids, including cholesterol, triglycerides, and lipoproteins.
• The liver is responsible for the breakdown of many waste products and toxic substances. The wastes are excreted in bile or travel to the kidneys, which excrete them in urine.

The liver is clearly a vital organ that supports almost every other organ in the body. Because of its strategic location and diversity of functions, the liver is also prone to many diseases, some of which cause loss of liver function. There is currently no way to compensate for the absence of liver function in the long term, although liver dialysis techniques can be used in the short term. An artificial liver has not yet been developed, so liver transplantation may be the only option for people with liver failure.

The gallbladder is a small, hollow, pouch-like organ that lies just under the right side of the liver (see Figure 15.6.5). It is about 8 cm (about 3 in) long and shaped like a tapered sac, with the open end continuous with the cystic duct. The gallbladder stores and concentrates bile from the liver until it is needed in the duodenum to help digest lipids. After the bile leaves the liver, it reaches the gallbladder through the cystic duct. At any given time, the gallbladder may store between 30 to 60 mL (1 to 2 oz) of bile. A hormone stimulated by the presence of fat in the duodenum signals the gallbladder to contract and force its contents back through the cystic duct and into the common bile duct to drain into the duodenum.

Pancreas

The pancreas is a glandular organ that is part of both the digestive system and the endocrine system. As shown in Figure 15.6.6, it is located in the abdomen behind the stomach, with the head of the pancreas surrounded by the duodenum of the small intestine. The pancreas is about 15 cm (almost 6 in) long, and it has two major ducts: the main pancreatic duct and the accessory pancreatic duct. Both of these ducts drain into the duodenum.

As an endocrine gland, the pancreas secretes several hormones, including insulin and glucagon, which circulate in the blood. The endocrine hormones are secreted by clusters of cells called pancreatic islets (or islets of Langerhans). As a digestive organ, the pancreas secretes many digestive enzymes and also bicarbonate, which helps neutralize acidic chyme after it enters the duodenum. The pancreas is stimulated to secrete its digestive substances when food in the stomach and duodenum triggers the release of endocrine hormones into the blood that reach the pancreas via the bloodstream. The pancreatic digestive enzymes are secreted by clusters of cells called acini, and they travel through the pancreatic ducts to the duodenum. In the duodenum, they help to chemically break down carbohydrates, proteins, lipids, and nucleic acids in chyme. The pancreatic digestive enzymes include:

• Amylase, which helps digest starch and other carbohydrates.
• Trypsin and chymotrypsin, which help digest proteins.
• Lipase, which helps digest lipids.
• Deoxyribonucleases and ribonucleases, which help digest nucleic acids.

 

Attributions

Figure 15.6.1

Scleral_Icterus by Sheila J. Toro on Wikimedia Commons is used under a  CC BY 4.0 (https://creativecommons.org/licenses/by/4.0) license.

Figure 15.6.2

Blausen_0428_Gallbladder-Liver-Pancreas_Location by BruceBlaus on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 15.6.3

Diagram_showing_the_two_lobes_of_the_liver_and_its_blood_supply_CRUK_376.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 15.6.4

Gallbladder by NIH Image Gallery on Flickr is used CC BY-NC 2.0 (https://creativecommons.org/licenses/by-nc/2.0/) license.

Figure 15.6.5

Gallbladder_(organ) (1) by BruceBlaus on Wikimedia Commons is used under a CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0) license. (See a full animation of this medical topic at blausen.com.)

Figure 15.6.6

Blausen_0698_PancreasAnatomy 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.

nature video. (2018, December 19). Scar wars: Repairing the liver. YouTube. https://www.youtube.com/watch?v=a0d1yvGcfzQ&feature=youtu.be

TED-Ed. (2014, November 25). What does the liver do? - Emma Bryce. YouTube. https://www.youtube.com/watch?v=wbh3SjzydnQ&feature=youtu.be

TED-Ed. (2015, February 19). What does the pancreas do? - Emma Bryce. YouTube. https://www.youtube.com/watch?v=8dgoeYPoE-0&feature=youtu.be

Created by CK-12 Foundation/Adapted by Christine Miller

If you had a skin rash like the one shown in Figure 15.7.1, you probably wouldn’t assume that it was caused by a digestive system disease. However, that’s exactly why the individual in the picture has a rash. He has a gastrointestinal (GI) tract disorder called Crohn’s disease. This disease is one of a group of GI tract disorders that are known collectively as inflammatory bowel disease. Unlike other inflammatory bowel diseases, signs and symptoms of Crohn’s disease may not be confined to the GI tract.

Inflammatory bowel disease (IBD) is a collection of inflammatory conditions primarily affecting the intestines. The two principal inflammatory bowel diseases are Crohn’s disease and ulcerative colitis. Unlike Crohn’s disease — which may affect any part of the GI tract and the joints, as well as the skin — ulcerative colitis mainly affects just the colon and rectum. Both diseases occur when the body’s own immune systemno post attacks the digestive system. Both diseases typically first appear in the late teens or early twenties, and occur equally in males and females.  Approximately 270,000 Canadians are currently living with IBD, 7,000 of which are children.  The annual cost of caring for these Canadians is estimated at $1.28 billion.  The number of cases of IBD has been steadily increasing and it is expected that by 2030 the number of Canadians suffering from IBD will grow to 400,000.

Crohn’s Disease

Crohn’s disease is a type of inflammatory bowel disease that may affect any part of the GI tract from the mouth to the anus, among other body tissues. The most commonly affected region is the ileum, which is the final part of the small intestine. Signs and symptoms of Crohn’s disease typically include abdominal pain, diarrhea (with or without blood), fever, and weight loss. Malnutrition because of faulty absorption of nutrients may also occur. Potential complications of Crohn’s disease include obstructions and abscesses of the bowel. People with Crohn’s disease are also at slightly greater risk than the general population of developing bowel cancer. Although there is a slight reduction in life expectancy in people with Crohn’s disease, if the disease is well-managed, affected people can live full and productive lives.  Approximately 135,000 Canadians are living with Crohn's disease.

Crohn’s disease is caused by a combination of genetic and environmental factors that lead to impairment of the generalized immune response (called innate immunity). The chronic inflammation of Crohn’s disease is thought to be the result of the immune system “trying” to compensate for the impairment. Dozens of genes are likely to be involved, only a few of which have been identified. Because of the genetic component, close relatives such as siblings of people with Crohn’s disease are many times more likely to develop the disease than people in the general population. Environmental factors that appear to increase the risk of the disease include smoking tobacco and eating a diet high in animal proteins. Crohn’s disease is typically diagnosed on the basis of a colonoscopy, which provides a direct visual examination of the inside of the colon and the ileum of the small intestine.

People with Crohn’s disease typically experience recurring periods of flare-ups followed by remission. There are no medications or surgical procedures that can cure Crohn’s disease, although medications such as anti-inflammatory or immune-suppressing drugs may alleviate symptoms during flare-ups and help maintain remission. Lifestyle changes, such as dietary modifications and smoking cessation, may also help control symptoms and reduce the likelihood of flare-ups. Surgery may be needed to resolve bowel obstructions, abscesses, or other complications of the disease.

Ulcerative Colitis

Ulcerative colitis is an inflammatory bowel disease that causes inflammation and ulcers (sores) in the colon and rectum. Unlike Crohn’s disease, other parts of the GI tract are rarely affected in ulcerative colitis. The primary symptoms of the disease are lower abdominal pain and bloody diarrhea. Weight loss, fever, and anemia may also be present. Symptoms typically occur intermittently with periods of no symptoms between flare-ups. People with ulcerative colitis have a considerably increased risk of colon cancer and should be screened for colon cancer more frequently than the general population. Ulcerative colitis, however, seems to primarily reduce the quality of life, and not the lifespan.

The exact cause of ulcerative colitis is not known. Theories about its cause involve immune system dysfunction, genetics, changes in normal gut bacteria, and lifestyle factors, such as a diet high in animal protein and the consumption of alcoholic beverages. Genetic involvement is suspected in part because ulcerative colitis tens to “run” in families. It is likely that multiple genes are involved. Diagnosis is typically made on the basis of colonoscopy and tissue biopsies.

Lifestyle changes, such as reducing the consumption of animal protein and alcohol, may improve symptoms of ulcerative colitis. A number of medications are also available to treat symptoms and help prolong remission. These include anti-inflammatory drugs and drugs that suppress the immune system. In cases of severe disease, removal of the colon and rectum may be required and can cure the disease.

Diverticulitis is a digestive disease in which tiny pouches in the wall of the large intestine become infected and inflamed. Symptoms typically include lower abdominal pain of sudden onset. There may also be fever, nausea, diarrhea or constipation, and blood in the stool. Having large intestine pouches called diverticula (see Figure 15.7.2) that are not inflamed is called diverticulosis. Diverticulosis is thought to be caused by a combination of genetic and environmental factors, and is more common in people who are obese. Infection and inflammation of the pouches (diverticulitis) occurs in about 10–25% of people with diverticulosis, and is more common at older ages. The infection is generally caused by bacteria.

Diverticulitis can usually be diagnosed with a CT scan and can be monitored with a colonoscopy (as seen in Figure 15.7.3). Mild diverticulitis may be treated with oral antibiotics and a short-term liquid diet. For severe cases, intravenous antibiotics, hospitalization, and complete bowel rest (no nourishment via the mouth) may be recommended. Complications such as abscess formation or perforation of the colon require surgery.

A peptic ulcer is a sore in the lining of the stomach or the duodenum (first part of the small intestine). If the ulcer occurs in the stomach, it is called a gastric ulcer. If it occurs in the duodenum, it is called a duodenal ulcer. The most common symptoms of peptic ulcers are upper abdominal pain that often occurs in the night and improves with eating. Other symptoms may include belching, vomiting, weight loss, and poor appetite. Many people with peptic ulcers, particularly older people, have no symptoms. Peptic ulcers are relatively common, with about ten per cent of people developing a peptic ulcer at some point in their life.

The most common cause of peptic ulcers is infection with the bacterium Helicobacter pylori, which may be transmitted by food, contaminated water, or human saliva (for example, by kissing or sharing eating utensils). Surprisingly, the bacterial cause of peptic ulcers was not discovered until the 1980s. The scientists who made the discovery are Australians Robin Warren and Barry J. Marshall. Although the two scientists eventually won a Nobel Prize for their discovery, their hypothesis was poorly received at first. To demonstrate the validity of their discovery, Marshall used himself in an experiment. He drank a culture of bacteria from a peptic ulcer patient and developed symptoms of peptic ulcer in a matter of days. His symptoms resolved on their own within a couple of weeks, but, at his wife's urging, he took antibiotics to kill any remaining bacteria. Marshall’s self-experiment was published in the Australian Medical Journal, and is among the most cited articles ever published in the journal.  Figure 15.7.4 shows how H. pylori cause peptic ulcers.

Another relatively common cause of peptic ulcers is chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen. Additional contributing factors may include tobacco smoking and stress, although these factors have not been demonstrated conclusively to cause peptic ulcers independent of H. pylori infection. Contrary to popular belief, diet does not appear to play a role in either causing or preventing peptic ulcers. Eating spicy foods and drinking coffee and alcohol were once thought to cause peptic ulcers. These lifestyle choices are no longer thought to have much (if any) of an effect on the development of peptic ulcers.

Peptic ulcers are typically diagnosed on the basis of symptoms or the presence of H. pylori in the GI tract. However, endoscopy (shown in Figure 15.7.5), which allows direct visualization of the stomach and duodenum with a camera, may be required for a definitive diagnosis. Peptic ulcers are usually treated with antibiotics to kill H. pylori, along with medications to temporarily decrease stomach acid and aid in healing. Unfortunately, H. pylori has developed resistance to commonly used antibiotics, so treatment is not always effective. If a peptic ulcer has penetrated so deep into the tissues that it causes a perforation of the wall of the stomach or duodenum, then emergency surgery is needed to repair the damage.

 

Gastroenteritis, also known as infectious diarrhea or stomach flu, is an acute and usually self-limiting infection of the GI tract by pathogens. Symptoms typically include some combination of diarrhea, vomiting, and abdominal pain. Fever, lack of energy, and dehydration may also occur. The illness generally lasts less than two weeks, even without treatment, but in young children it is potentially deadly. Gastroenteritis is very common, especially in poorer nations. Worldwide, up to five billion cases occur each year, resulting in about 1.4 million deaths.

Commonly called “stomach flu,” gastroenteritis is unrelated to the influenza virus, although viruses are the most common cause of the disease (see Figure 15.7.6). In children, rotavirus is most often the cause which is why the British Columbia immunization schedule now includes a rotovirus vaccine. Norovirus is more likely to be the cause of gastroenteritis in adults. Besides viruses, other potential causes of gastroenteritis include fungi, bacteria (most often E. coli or Campylobacter jejuni), and protozoa(including Giardia lamblia, more commonly called Beaver Fever, described below). Transmission of pathogens may occur due to eating improperly prepared foods or foods left to stand at room temperature, drinking contaminated water, or having close contact with an infected individual.

Gastroenteritis is less common in adults than children, partly because adults have acquired immunity after repeated exposure to the most common infectious agents. Adults also tend to have better hygiene than children. If children have frequent repeated incidents of gastroenteritis, they may suffer from malnutrition, stunted growth, and developmental delays. Many cases of gastroenteritis in children can be avoided by giving them a rotavirus vaccine. Frequent and thorough handwashing can cut down on infections caused by other pathogens.

Treatment of gastroenteritis generally involves increasing fluid intake to replace fluids lost in vomiting or diarrhea. Oral rehydration solution, which is a combination of water, salts, and sugar, is often recommended. In severe cases, intravenous fluids may be needed. Antibiotics are not usually prescribed, because they are ineffective against viruses that cause most cases of gastroenteritis.

Giardiasis, popularly known as beaver fever, is a type of gastroenteritis caused by a GI tract parasite, the single-celled protozoan Giardia lamblia (pictured in Figure 15.7.7). In addition to human beings, the parasite inhabits the digestive tract of a wide variety of domestic and wild animals, including cows, rodents, and sheep, as well as beavers (hence its popular name). Giardiasis is one of the most common parasitic infections in people the world over, with hundreds of millions of people infected worldwide each year.

Transmission of G. lamblia is via a fecal-oral route (as in, you got feces in your food). Those at greatest risk include travelers to countries where giardiasis is common, people who work in child-care settings, backpackers and campers who drink untreated water from lakes or rivers, and people who have close contact with infected people or animals in other settings. In Canada, Giardia is the most commonly identified intestinal parasite and approximately 3,000 Canadians will contract the parasite annually.

Symptoms of giardiasis can vary widely. About one-third third of people with the infection have no symptoms, whereas others have severe diarrhea with poor absorption of nutrients. Problems with absorption occur because the parasites inhibit intestinal digestive enzyme production, cause detrimental changes in microvilli lining the small intestine, and kill off small intestinal epithelial cells. The illness can result in weakness, loss of appetite, stomach cramps, vomiting, and excessive gas. Without treatment, symptoms may continue for several weeks. Treatment with anti-parasitic medications may be needed if symptoms persist longer or are particularly severe.

Attributions

Figure 15.7.1

BADAS_Crohn by Dayavathi Ashok and Patrick Kiely/ Journal of medical case reports on Wikimedia Commons is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0) license.

Figure 15.7.2

512px-Ds00070_an01934_im00887_divert_s_gif.webp by Lfreeman04  on Wikimedia Commons is used under a CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0) license.

Figure 15.7.3

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

Figure 15.7.4

H_pylori_ulcer_diagram by Y_tambe on Wikimedia Commons is used under a CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0/) license.

Figure 15.7.5

1024px-Endoscopy_training by Yuya Tamai on Wikimedia Commons is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0) license.

Figure 15.7.6

Gastroenteritis_viruses by Dr. Graham Beards [en:User:Graham Beards] at en.wikipedia on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 15.7.7

Giardia_lamblia_SEM_8698_lores by Janice Haney Carr from CDC/ Public Health Image Library (PHIL) ID# 8698 on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/public_domain).

References

Ashok, D., & Kiely, P. (2007). Bowel associated dermatosis - arthritis syndrome: a case report. Journal of medical case reports, 1, 81. https://doi.org/10.1186/1752-1947-1-81

Marshall, B. J., Armstrong, J. A., McGechie, D. B., & Glancy, R. J. (1985). Attempt to fulfil Koch's postulates for pyloric Campylobacter. The Medical Journal of Australia, 142(8), 436–439.

Marshall, B. J., McGechie, D. B., Rogers, P. A., & Glancy, R. J. (1985). Pyloric campylobacter infection and gastroduodenal disease. The Medical Journal of Australia, 142(8), 439–444.

TED-Ed. (2017, September 28). The surprising cause of stomach ulcers - Rusha Modi. YouTube. https://www.youtube.com/watch?v=V_U6czbDHLE&feature=youtu.be

TED-Ed. (2018, January 4). Who's at risk for colon cancer? - Amit H. Sachdev and Frank G. Gress. YouTube. https://www.youtube.com/watch?v=H5zin8jKeT0&feature=youtu.be

Created by CK-12 Foundation/Adapted by Christine Miller

From Bram Stoker’s famous novel about Count Dracula, to films such as Van Helsing and the Twilight Saga, fantasies featuring vampires (like the one in Figure 14.5.1) have been popular for decades. Vampires, in fact, are found in centuries-old myths from many cultures. In such myths, vampires are generally described as creatures that drink blood — preferably of the human variety — for sustenance. Dracula, for example, is based on Eastern European folklore about a human who attains immortality (and eternal damnation) by drinking the blood of others.

The average adult body contains between 4.7 and 5.7 litres of blood. More than half of that amount is fluid. Most of the rest of that amount consists of blood cells. The relative amounts of the various components in blood are illustrated in Figure 14.5.2. The components are also described in detail below.

Blood performs many important functions in the body. Major functions of blood include:

• Supplying tissues with oxygen, which is needed by all cells for aerobic cellular respiration.
• Supplying cells with nutrients, including glucose, amino acids, and fatty acids.
• Removing metabolic wastes from cells, including carbon dioxide, urea, and lactic acid.
• Helping to defend the body from pathogens and other foreign substances.
• Forming clots to seal broken blood vessels and stop bleeding.
• Transporting hormones and other messenger molecules.
• Regulating the pH of the body, which must be kept within a narrow range (7.35 to 7.45).
• Helping regulate body temperature (through vasoconstriction and vasodilation).

Plasma is the liquid component of human blood. It makes up about 55% of blood by volume. It is about 92% water, and contains many dissolved substances. Most of these substances are proteins, but plasma also contains trace amounts of glucose, mineral ions, hormones, carbon dioxide, and other substances. In addition, plasma contains blood cells. When the cells are removed from plasma, as in Figure 14.5.2 above, the remaining liquid is clear but yellow in colour.

The cells in blood include erythrocytes, leukocytes, and thrombocytes. These different types of blood cells are shown in the photomicrograph (Figure 14.5.3) and described in the sections that follow.

Erythrocytes

The most numerous cells in blood are red blood cells, also called erythrocytes. One microlitre of blood contains between 4.2 and 6.1 million red blood cells, and red blood cells make up about 25% of all the cells in the human body. The cytoplasm of a mature erythrocyte is almost completely filled with hemoglobin, the iron-containing protein that binds with oxygen and gives the cell its red colour. In order to provide maximum space for hemoglobin, mature erythrocytes lack a cell nucleus and most organelles. They are little more than sacks of hemoglobin.

Erythrocytes also carry proteins called antigens that determine blood type. Blood type is a genetic characteristic. The best known human blood type systems are the ABO and Rhesus systems.

• In the ABO system, there are two common antigens, called antigen A and antigen B. There are four ABO blood types, A (only A antigen), B (only B antigen), AB (both A and B antigens), and O (neither A nor B antigen). The ABO antigens are illustrated in Figure 14.5.4.
• In the Rhesus system, there is just one common antigen. A person may either have the antigen (Rh+) or lack the antigen (Rh-).

Blood type is important for medical reasons. A person who needs a blood transfusion must receive blood of a compatible type. Blood that is compatible lacks antigens that the patient's own blood also lacks. For example, for a person with type A blood (no B antigen), compatible types include any type of blood that lacks the B antigen. This would include type A blood or type O blood, but not type AB or type B blood. If incompatible blood is transfused, it may cause a potentially life-threatening reaction in the patient’s blood.

Leukocytes

Leukocytes (also called white blood cells) are cells in blood that defend the body against invading microorganisms and other threats. There are far fewer leukocytes than red blood cells in blood. There are normally only about 1,000 to 11,000 white blood cells per microlitre of blood. Unlike erythrocytes, leukocytes have a nucleus. White blood cells are part of the body’s immune systemno post. They destroy and remove old or abnormal cells and cellular debris, as well as attack pathogens and foreign substances. There are five main types of white blood cells, which are described in Table 14.5.1: neutrophils, eosinophils, basophils, lymphocytes, and monocytes. The five types differ in their specific immune functions.

Table 14.5.1: Major Types of White Blood Cells

Type of Leukocyte	Per cent of All Leukocytes	Main Function(s)
Neutrophil	62%	Phagocytize (engulf and destroy) bacteria and fungi in blood.
Eosinophil	2%	Attack and kill large parasites; carry out allergic responses.
Basophil	less than 1%	Release histamines in inflammatory responses.
Lymphocyte	30%	Attack and destroy virus-infected and tumor cells; create lasting immunity to specific pathogens.
Monocyte	5%	Phagocytize pathogens and debris in tissues.

Thrombocytes

Thrombocytes, also called platelets, are actually cell fragments. Like erythrocytes, they lack a nucleus and are more numerous than white blood cells. There are about 150 thousand to 400 thousand thrombocytes per microlitre of blood.

The main function of thrombocytes is blood clotting, or coagulation. This is the process by which blood changes from a liquid to a gel, forming a plug in a damaged blood vessel. If blood clotting is successful, it results in hemostasis, which is the cessation of blood loss from the damaged vessel. A blood clot consists of both platelets and proteins, especially the protein fibrin. You can see a scanning electron microscope photomicrograph of a blood clot in Figure 14.5.5.

 

Coagulation begins almost instantly after an injury occurs to the endothelium of a blood vessel. Thrombocytes become activated and change their shape from spherical to star-shaped, as shown in Figure 14.5.6. This helps them aggregate with one another (stick together) at the site of injury to start forming a plug in the vessel wall. Activated thrombocytes also release substances into the blood that activate additional thrombocytes and start a sequence of reactions leading to fibrin formation. Strands of fibrin crisscross the platelet plug and strengthen it, much as rebar strengthens concrete.

Formation and Degradation of Blood Cells

Blood is considered a connective tissue, because blood cells form inside bones. All three types of blood cells are made in red marrow within the medullary cavity of bones in a process called hematopoiesis. Formation of blood cells occurs by the proliferation of stem cells in the marrow. These stem cells are self-renewing — when they divide, some of the daughter cells remain stem cells, so the pool of stem cells is not used up. Other daughter cells follow various pathways to differentiate into the variety of blood cell types. Once the cells have differentiated, they cannot divide to form copies of themselves.

Eventually, blood cells die and must be replaced through the formation of new blood cells from proliferating stem cells. After blood cells die, the dead cells are phagocytized (engulfed and destroyed) by white blood cells, and removed from the circulation. This process most often takes place in the spleen and liver.

Many human disorders primarily affect the blood. They include cancers, genetic disorders, poisoning by toxins, infections, and nutritional deficiencies.

• Leukemia is a group of cancers of the blood-forming tissues in the bone marrow. It is the most common type of cancer in children, although most cases occur in adults. Leukemia is generally characterized by large numbers of abnormal leukocytes. Symptoms may include excessive bleeding and bruising, fatigue, fever, and an increased risk of infections. Leukemia is thought to be caused by a combination of genetic and environmental factors.
• Hemophilia refers to any of several genetic disorders that cause dysfunction in the blood clotting process. People with hemophilia are prone to potentially uncontrollable bleeding, even with otherwise inconsequential injuries. They also commonly suffer bleeding into the spaces between joints, which can cause crippling.
• Carbon monoxide poisoning occurs when inhaled carbon monoxide (in fumes from a faulty home furnace or car exhaust, for example) binds irreversibly to the hemoglobin in erythrocytes. As a result, oxygen cannot bind to the red blood cells for transport throughout the body, and this can quickly lead to suffocation. Carbon monoxide is extremely dangerous, because it is colourless and odorless, so it cannot be detected in the air by human senses.
• HIV is a virus that infects certain types of leukocytes and interferes with the body’s ability to defend itself from pathogens and other causes of illness. HIV infection may eventually lead to AIDS (acquired immunodeficiency syndrome). AIDS is characterized by rare infections and cancers that people with a healthy immune systemno post almost never acquire.
• Anemia is a disorder in which the blood has an inadequate volume of erythrocytes, reducing the amount of oxygen that the blood can carry, and potentially causing weakness and fatigue. These and other signs and symptoms of anemia are shown in Figure 14.5.8. Anemia has many possible causes, including excessive bleeding, inherited disorders (such as sickle cell hemoglobin), or nutritional deficiencies (iron, folate, or B12). Severe anemia may require transfusions of donated blood.

Donating blood saves lives. In fact, with each blood donation, as many as three lives may be saved. According to Government Canada, up to 52% of Canadians have reported that they or a family member have needed blood or blood products at some point in their lifetime. Many donors agree that the feeling that comes from knowing you have saved lives is well worth the short amount of time it takes to make a blood donation. Nonetheless, only a minority of potential donors actually donate blood. There are many myths about blood donation that may help explain the small percentage of donors. Knowing the facts may reaffirm your decision to donate if you are already a donor — and if you aren’t a donor already, getting the facts may help you decide to become one.

Myth	Reality
"Your blood might become contaminated with an infection during the donation."	There is no risk of contamination because only single-use, disposable catheters, tubing, and other equipment are used to collect blood for a donation.
"You are too old (or too young) to donate blood."	There is no upper age limit on donating blood, as long as you are healthy. The minimum age is 16 years.
"You can’t donate blood if you have high blood pressure."	As long as your blood pressure is below 180/100 at the time of donation, you can give blood. Even if you take blood pressure medication to keep your blood pressure below this level, you can donate.
"You can’t give blood if you have high cholesterol."	Having high cholesterol does not affect your ability to donate blood. Taking cholesterol-lowering medication also does not disqualify you.
"You can’t donate blood if you have had a flu shot."	Having a flu shot has no effect on your ability to donate blood. You can even donate on the same day that you receive a flu shot.
"You can’t donate blood if you take medication."	As long as you are healthy, in most cases, taking medication does not preclude you from donating blood.
"Your blood isn’t needed if it’s a common blood type."	All types of blood are in constant demand.

Attributions

Figure 14.5.1

vampire_PNG32 from pngimg.com is used under a CC BY-NC 4.0 (https://creativecommons.org/licenses/by-nc/4.0/) license.

Figure 14.5.2

Blood-centrifugation-scheme by KnuteKnudsen at English Wikipedia on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 14.5.3

SEM_blood_cells by Bruce Wetzel and Harry Schaefer (Photographers)/ NCI AV-8202-3656 on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/en:Public_domain).

Figure 14.5.4

ABO_blood_type.svg by InvictaHOG on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/en:Public_domain).

Figure 14.5.5

Blood_clot_in_scanning_electron_microscopy by Janice Carr from CDC/ Public Health Image LIbrary (PHIL) ID #7308 on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/en:Public_domain).

Figure 14.5.6

Blausen_0740_Platelets by BruceBlaus on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license. 

Figure 14.5.7

Platelet_Party_900x by Awkward Yeti (used with permission of the author) © All Rights Reserved

Figure 14.5.8

Symptoms_of_anemia.svg by Mikael Häggström on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/en:public_domain).

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.

Blood, organ and tissue donation. (2020, April 28). Government of Canada. https://www.canada.ca/en/public-health/services/healthy-living/blood-organ-tissue-donation.html#a3

Canadian Blood Services. (n.d.). There is an immediate need for blood as demand is rising. https://www.blood.ca

Science Plus. (2016, March 2). Can synthetic blood help the world's blood shortage? https://www.youtube.com/watch?v=hgp8LtwFSBA&feature=youtu.be

TED. (2014, November 20). Joe Landolina: This gel can make you stop bleeding instantly. YouTube. https://www.youtube.com/watch?v=e-5wqwp64MM&feature=youtu.be

TED-Ed. (2020, January 27). How bones make blood - Melody Smith. YouTube. https://www.youtube.com/watch?v=1Qfmkd6C8u8&feature=youtu.be

The central nervous system organ inside the skull that is the control center of the nervous system.

Created by CK-12 Foundation/Adapted by Christine Miller

Art in a Cup

Who knew that a cup of coffee could also be a work of art? A talented barista can make coffee look as good as it tastes. If you are a coffee drinker, you probably know that coffee can also affect your mental state. It can make you more alert, and it may improve your concentration. That’s because the caffeine in coffee is a psychoactive drug. In fact, caffeine is the most widely consumed psychoactive substance in the world. In North America, for example, 90 per cent of adults consume caffeine daily.

Psychoactive drugs are substances that change the function of the brain and result in alterations of mood, thinking, perception, and/or behavior. Psychoactive drugs may be used for many purposes, including therapeutic, ritual, or recreational purposes. Besides caffeine, other examples of psychoactive drugs include cocaine, LSD, alcohol, tobacco, codeine, and morphine. Psychoactive drugs may be legal prescription medications (codeine and morphine), legal nonprescription drugs (alcohol and tobacco), or illegal drugs (cocaine and LSD).

Cannabis (or marijuana) is also a psychoactive drug that while illegal in many countries is legal for use in Canada by individuals over the age of 19 years. Legal prescription medications (such as opioids) are also used illegally by increasingly large numbers of people. Some legal drugs, such as alcohol and nicotine, are readily available almost everywhere, as illustrated by the images below.

Figure 8.8.2 These psychoactive drugs are legal and accessible almost anywhere.  

Psychoactive drugs are divided into different classes based on their pharmacological effects. Several classes are listed below, along with examples of commonly used drugs in each class.

• Stimulants are drugs that stimulate the brain and increase alertness and wakefulness. Examples of stimulants include caffeine, nicotine, cocaine, and amphetamines (such as Adderall).
• Depressants are drugs that calm the brain, reduce anxious feelings, and induce sleepiness. Examples of depressants include ethanol (in alcoholic beverages) and opioids, such as codeine and heroin.
• Anxiolytics are drugs that have a tranquilizing effect and inhibit anxiety. Examples of anxiolytic drugs include benzodiazepines (such as diazepam/Valium), barbiturates (such as phenobarbital), opioids, and antidepressant drugs (such as sertraline/Zoloft).
• Euphoriants are drugs that bring about a state of euphoria, or intense feelings of well-being and happiness. Examples of euphoriants include the so-called "club drug" MDMA (ecstasy), amphetamines, ethanol, and opioids (such as morphine).
• Hallucinogens are drugs that can cause hallucinations and other perceptual anomalies. They also cause subjective changes in thoughts, emotions, and consciousness. Examples of hallucinogens include LSD, mescaline, nitrous oxide, and psilocybin.
• Empathogens are drugs that produce feelings of empathy, or sympathy with other people. Examples of empathogens include amphetamines and MDMA.

Many psychoactive drugs have multiple effects, so they may be placed in more than one class. One example is MDMA, pictured below, which may act both as a euphoriant and as an empathogen. In some people, MDMA may also have stimulant or hallucinogenic effects. As of 2016, MDMA had no accepted medical uses, but it was undergoing testing for use in the treatment of post-traumatic stress disorder and certain other types of anxiety disorders.

Psychoactive drugs generally produce their effects by affecting brain chemistry, which in turn may cause changes in a person’s mood, thinking, perception, and behavior. Each drug tends to have a specific action on one or more neurotransmitters or neurotransmitter receptors in the brain. Generally, they act as either agonists or antagonists.

• Agonists are drugs that increase the activity of particular neurotransmitters. They might act by promoting the synthesis of the neurotransmitters, reducing their reuptake from synapses, or mimicking their action by binding to receptors for the neurotransmitters.
• Antagonists are drugs that decrease the activity of particular neurotransmitters. They might act by interfering with the synthesis of the neurotransmitters or by blocking their receptors so the neurotransmitters cannot bind to them.

Consider the example of the neurotransmitter GABA. This is one of the most common neurotransmitters in the brain, and it normally has an inhibitory effect on cells. GABA agonists — which increase its activity — include ethanol, barbiturates, and benzodiazepines, among other psychoactive drugs. All of these drugs work by promoting the activity of GABA receptors in the brain.

You may have been prescribed psychoactive drugs by your doctor. For example, your doctor may have prescribed you an opioid drug, such as codeine for pain (most likely in the form of Tylenol with added codeine). Chances are you also use nonprescription psychoactive drugs (like caffeine) for mental alertness. These are just two of the many possible uses of psychoactive drugs.

Medical Uses

General anesthesia is one use of psychoactive drugs in medicine. With general anesthesia, pain is blocked and unconsciousness is induced. General anesthetics are most often used during surgical procedures and may be administered in gaseous form, as in Figure 8.8.4. General anesthetics include the drugs halothane and ketamine. Other psychoactive drugs are used to manage pain without affecting consciousness. They may be prescribed either for acute pain in cases of trauma (such as broken bones) or for chronic pain caused by arthritis, cancer, or fibromyalgia. Most often, the drugs used for pain control are opioids, such as morphine and codeine.

Many psychiatric disorders are also managed with psychoactive drugs. Antidepressants like sertraline, for example, are used to treat depression, anxiety, and eating disorders. Anxiety disorders may also be treated with anxiolytics, such as buspirone and diazepam. Stimulants (such as amphetamines) are used to treat attention deficit disorder. Antipsychotics (such as clozapine and risperidone) — as well as mood stabilizers, such as lithium — are used to treat schizophrenia and bipolar disorder.

Ritual Uses

Certain psychoactive drugs, particularly hallucinogens, have been used for ritual purposes since prehistoric times. For example, Native Americans have used the mescaline-containing peyote cactus (pictured in Figure 8.8.5) for religious ceremonies for as long as 5,700 years. In prehistoric Europe, the mushroom Amanita muscaria, which contains a hallucinogenic drug called muscimol, was used for similar purposes. Various other psychoactive drugs — including jimsonweed, psilocybin mushrooms, and cannabis — have also been used for millennia, by various peoples, for ritual purposes.

 

The recreational use of psychoactive drugs generally has the purpose of altering one’s consciousness and creating a feeling of euphoria commonly called a “high.” Some of the drugs used most commonly for recreational purposes are cannabis, ethanol (alcohol), opioids, and stimulants (such as nicotine). Hallucinogens are also used recreationally, primarily for the alterations they cause in thinking and perception.

Some investigators have suggested that the urge to alter one’s state of consciousness is a universal human drive, similar to the drive to satiate thirst, hunger, or sexual desire. They think that this instinct is even present in children, who may attain an altered state by repetitive motions, such as spinning or swinging. Some nonhuman animals also exhibit a drive to experience altered states. They may consume fermented berries or fruit and become intoxicated. The way cats respond to catnip (see Figure 8.8.6) is another example.

Addiction, Dependence, and Rehabilitation

Psychoactive substances often bring about subjective changes that the user may find pleasant (euphoria) or advantageous (increased alertness). These changes are rewarding and positively reinforcing, so they have the potential for misuse, addiction, and dependence. Addiction refers to the compulsive use of a drug, despite negative consequences that such use may entail. Sustained use of an addictive drug may produce dependence on the drug. Dependence may be physical and/or psychological. It occurs when cessation of drug use produces withdrawal symptoms. Physical dependence produces physical withdrawal symptoms, which may include tremors, pain, seizures, or insomnia. Psychological dependence produces psychological withdrawal symptoms, such as anxiety, depression, paranoia, or hallucinations.

Rehabilitation for drug dependence and addiction typically involves psychotherapy, which may include both individual and group therapy. Organizations such as Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) may also be helpful for people trying to recover from addiction. These groups are self-described as international mutual aid fellowships, and their primary purpose is to help addicts achieve and maintain sobriety. In some cases, rehabilitation is aided by the temporary use of psychoactive substances that reduce cravings and withdrawal symptoms without creating addiction themselves. The drug methadone, for example, is commonly used to treat heroin addiction.

In North America, a lot of media attention is currently given to a rising tide of opioid addiction and overdose deaths. Opioids are drugs derived from the opium poppy or synthetic versions of such drugs. They include the illegal drug heroin, as well as prescription painkillers such as codeine, morphine, hydrocodone, oxycodone, and fentanyl. In 2016, fentanyl received wide media attention when it was announced that an accidental fentanyl overdose was responsible for the death of music icon Prince. Fentanyl is an extremely strong and dangerous drug, said to be 50 to 100 times stronger than morphine, making risk of overdose death from fentanyl very high.

The dramatic increase in opioid addiction and overdose deaths has been called an opioid epidemic. It is considered to be the worst drug crisis in Canadian history. Consider the following facts:

• In 2016, there were almost 2,500 opioid-related deaths in Canada — almost 7 per day.
• The number of prescriptions written for opioids quadrupled between 1999 and 2010.  If you have been prescribed codeine, fentanyl, morphine, oxycodone, hydromorphone or medical heroin, then you have been prescribed an opiate.
• There are many long-term health effects of using opioids, which include:
  • Increased tolerance to the drug.
  • Liver damage.
  • Substance use disorder or addiction.

Doctors, public health professionals, and politicians have all called for new policies, funding, programs, and laws to address the opioid epidemic. Changes that have already been made include a shift from criminalizing to medicalizing the problem, more treatment programs, and more widespread distribution and use of the opioid-overdose antidote naloxone (Narcan). Opioids can slow or stop a person's breathing, which is what usually causes overdose deaths. Naloxone helps the person wake up and keeps them breathing until emergency medical treatment can be provided.

What, if anything, will work to stop the opioid epidemic in Canada and the United States? Keep watching the news to find out.

 

Attributions

Figure 8.8.1

Cappucino Art by drew-coffman-tZKwLRO904E [photo] by Drew Coffman on Unsplash is used under the Unsplash License (https://unsplash.com/license).

Figure 8.8.2

• 3804, Saint-Laurent, Montreal - Cannabis Culture shop by Exile on Ontario St (Montreal, Canada) on Wikimedia Commons is used under a CC BY SA 2.0 (https://creativecommons.org/licenses/by-sa/2.0/deed.en) license.
• Drive Through Cigarette Store by Cosmo Spacely on Flickr is used under CC BY-NC-SA 2.0 (https://creativecommons.org/licenses/by-nc-sa/2.0/) license.
• Franklin-Nicollet Liquors by Max Sparber on Flickr is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/deed.en) license.

Figure 8.8.3

Ecstasy_monogram by Drug Enforcement Administration on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

Figure 8.8.4

US Navy 030513-N-1577S-001 Lt. Cmdr. Joe Casey, Ship's Anesthetist, trains on anesthetic procedures with Hospital Corpsman 3rd Class Eric Wichman aboard USS Nimitz (CVN 68) by U.S. Navy photo by Photographer’s Mate Airman Timothy F. Sosais on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

Figure 8.8.5

Peyote Lophophora_williamsii_pm by Peter A. Mansfeld on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/deed.en) license.

Figure 8.8.6

Cat under effects of catnip/Self Indulgence by Katieb50 on Flickr is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/deed.en) license.

 

References

Alcoholics Anonymous World Services, Inc. (n.d.). Regional correspondent U.S. and Canada [website]. https://www.aa.org/pages/en_US/regional-correspondent-us-and-canada

Belzak, L., & Halverson, J. (2018). The opioid crisis in Canada: a national perspective. La crise des opioïdes au Canada : une perspective nationale. Health promotion and chronic disease prevention in Canada : research, policy and practice, 38(6), 224–233. https://doi.org/10.24095/hpcdp.38.6.02

British Columbia Regional Service Committee of Narcotics Anonymous. (n.d.). Welcome to the B.C. region of N.A. [website]. https://www.bcrna.ca/

Centers for Disease Control and Prevention (CDC). (2011 November 4). Vital signs: overdoses of prescription opioid pain relievers—United States, 1999–2008. Morbidity and Mortality Weekly Report (MMWR),60(43):1487-1492. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6043a4.htm

TED-Ed. (2017, June 29). How do drugs affect the brain? - Sara Garofalo. YouTube. https://www.youtube.com/watch?v=8qK0hxuXOC8&feature=youtu.be

TED-Ed. (2017, July 17). How does caffeine keep us awake? - Hanan Qasim. YouTube. https://www.youtube.com/watch?v=foLf5Bi9qXs&feature=youtu.be

TED-Ed. (2019, December 2). Is marijuana bad for your brain? - Anees Bahji. YouTube. https://www.youtube.com/watch?v=Nlcr1jd_Tok&feature=youtu.be

 

A signal transmitted along a nerve fiber.

Created by CK-12 Foundation/Adapted by Christine Miller

These moms (Figure 12.5.1) are setting a great example for their children by engaging in physical exercise. Adopting a habit of regular physical exercise is one of the most important ways to maintain fitness and good health. From higher self-esteem to a healthier heart, physical exercise can have a positive effect on virtually all aspects of health, including physical, mental, and emotional health.

Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness. We generally think of physical exercise as activities that are undertaken for the main purpose of improving physical fitness and health. However, physical activities that are undertaken for other purposes may also count as physical exercise. Scrubbing a floor, raking a lawn, or playing active games with young children or a pet are all activities that can have fitness and health benefits, even though they generally are not done mainly for this purpose.

How much physical exercise should people get? In the Canada, both the Canadian Food Guide and the Canadian Society for Exercise Physiology  recommend that every child and  adult who is able should participate in moderate exercise for a minimum of 60 minutes a day. This might include walking, swimming, and/or household or yard work.

Physical exercise can be classified into three types, depending on the effects it has on the body: aerobic exercise, anaerobic exercise, and flexibility exercise. Many specific examples of physical exercise (including playing soccer and rock climbing) can be classified as more than one type.

Aerobic Exercise

Aerobic exerciseis any physical activity in which muscles are used at well below their maximum contraction strength, but for long periods of time. Aerobic exercise uses a relatively high percentage of slow-twitch muscle fibres that consume a large amount of oxygen. The main goal of aerobic exercise is to increase cardiovascular endurance, although it can have many other benefits, including muscle toning. Examples of aerobic exercise include cycling, swimming, brisk walking, jumping rope, rowing, hiking, tennis, and kayaking as shown in Figure 12.5.2 .

Anaerobic Exercise

Anaerobic exercise is any physical activity in which muscles are used at close to their maximum contraction strength, but for relatively short periods of time. Anaerobic exercise uses a relatively high percentage of fast-twitch muscle fibres that consume a small amount of oxygen. Goals of anaerobic exercise include building and strengthening muscles, as well as improving bone strength, balance, and coordination. Examples of anaerobic exercise include push-ups, lunges, sprinting, interval training, resistance training, and weight training (such as biceps curls with a dumbbell, as pictured in Figure 12.5.3).

Flexibility Exercise

Flexibility exercise is any physical activity that stretches and lengthens muscles. Goals of flexibility exercise include increasing joint flexibility, keeping muscles limber, and improving the range of motion, all of which can reduce the risk of injury. Examples of flexibility exercise include stretching, yoga (as in Figure 12.5.4), and tai chi.

Many studies have shown that physical exercise is positively correlated with a diversity of health benefits. Some of these benefits include maintaining physical fitness, losing weight and maintaining a healthy weight, regulating digestive health, building and maintaining healthy bone density, increasing muscle strength, improving joint mobility, strengthening the immune system, boosting cognitive ability, and promoting psychological well-being. Some studies have also found a significant positive correlation between exercise and both quality of life and life expectancy. People who participate in moderate to high levels of physical activity have been shown to have lower mortality rates than people of the same ages who are not physically active and daily exercise has been shown to increase life expectancy up to an average of five years.

The underlying physiological mechanisms explaining why exercise has these positive health benefits are not completely understood. However, developing research suggests that many of the benefits of exercise may come about because of the role of skeletal muscles as endocrine organs. Contracting muscles release hormones called myokines, which promote tissue repair and the growth of new tissue. Myokines also have anti-inflammatory effects, which, in turn, reduce the risk of developing inflammatory diseases. Exercise also reduces levels of cortisol, the adrenal cortex stress hormone that may cause many health problems — both physical and mental — at sustained high levels.

Cardiovascular Benefits of Physical Exercise

The beneficial effects of exercise on the cardiovascular system are well documented. Physical inactivity has been identified as a risk factor for the development of coronary artery disease. There is also a direct correlation between physical inactivity and cardiovascular disease mortality. Physical exercise, in contrast, has been demonstrated to reduce several risk factors for cardiovascular disease, including hypertension (high blood pressure), “bad” cholesterol (low-density lipoproteins), high total cholesterol, and excess body weight. Physical exercise has also been shown to increase “good” cholesterol (high-density lipoproteins), insulin sensitivity, the mechanical efficiency of the heart, and exercise tolerance, which is the ability to perform physical activity without undue stress and fatigue.

Cognitive Benefits of Physical Exercise

Physical exercise has been shown to help protect people from developing neurodegenerative disorders, such as dementia. A 30-year study of almost 2,400 men found that those who exercised regularly had a 59 per cent reduction in dementia when compared with those who did not exercise. Similarly, a review of cognitive enrichment therapies for the elderly found that physical activity — in particular, aerobic exercise — can enhance the cognitive function of older adults. Anecdotal evidence suggests that frequent exercise may even help reverse alcohol-induced brain damage. There are several possible reasons why exercise is so beneficial for the brain. Physical exercise:

• Increases blood flow and oxygen availability to the brain.
• Increases growth factors that promote new brain cells and new neuronal pathways in the brain.
• Increases levels of neurotransmitters (such as serotonin), which increase memory retention, information processing, and cognition.

Mental Health Benefits of Physical Exercise

Numerous studies suggest that regular aerobic exercise works as well as pharmaceutical antidepressants in treating mild-to-moderate depression. A possible reason for this effect is that exercise increases the biosynthesis of at least three neurochemicals that may act as euphoriants. The euphoric effect of exercise is well known. Distance runners may refer to it as “runner’s high,” and people who participate in crew (as in Figure 12.5.5) may refer to it as “rower’s high.” Because of these effects, health care providers often promote the use of aerobic exercise as a treatment for depression.

Additional mental health benefits of physical exercise include reducing stress, improving body image, and promoting positive self-esteem. Conversely, there is evidence to suggest that being sedentary is associated with increased risk of anxiety.

Sleep Benefits of Physical Exercise

A recent review of published scientific research suggests that exercise generally improves sleep for most people, and helps sleep disorders, such as insomnia. In fact, exercise is the most recommended alternative to sleeping pills for people with insomnia. For sleep benefits, the optimum time to exercise may be four to eight hours before bedtime, although exercise at any time of day seems to be beneficial. The only possible exception is heavy exercise undertaken shortly before bedtime, which may actually interfere with sleep.

Other Benefits of Physical Exercise

Some studies suggest that physical activity may benefit the immune systemno post. For example, moderate exercise has been found to be associated with a decreased incidence of upper respiratory tract infections. Evidence from many studies has found a correlation between physical exercise and reduced death rates from cancer, specifically breast cancer and colon cancer. Physical exercise has also been shown to reduce the risk of type 2 diabetes and obesity.

Not everyone benefits equally from physical exercise. When participating in aerobic exercise, most people will have a moderate increase in their endurance, but some people will as much as double their endurance. Some people, on the other hand, will show little or no increase in endurance from aerobic exercise. Genetic differences in slow-twitch and fast-twitch skeletal muscle fibres may play a role in these different results. People with more slow-twitch fibres may be able to develop greater endurance, because these muscle fibres have more capillaries, mitochondria, and myoglobin than fast-twitch fibres. As a result, slow-twitch fibres can carry more oxygen and sustain aerobic activity for a longer period of time than fast-twitch fibres. Studies show that endurance athletes (like the marathoner pictured in Figure 12.5.6) generally do tend to have a higher proportion of slow-twitch fibres than other people.

There is also great variation in individual responses to muscle building as a result of anaerobic exercise. Some people have a much greater capacity to increase muscle size and strength, whereas other people never develop large muscles, no matter how much they exercise them. People who have more fast-twitch than slow-twitch muscle fibres may be able to develop bigger, stronger muscles, because fast-twitch muscle fibres contribute more to muscle strength and have greater potential to increase in mass. Evidence suggests that athletes who excel at power activities (such as throwing and jumping) tend to have a higher proportion of fast-twitch fibres than do endurance athletes.

Is it possible to exercise too much? Can too much exercise be harmful? Evidence suggests that some adverse effects may occur if exercise is extremely intense and the body is not given proper rest between exercise sessions. Athletes who train for multiple marathons have been shown to develop scarring of the heart and heart rhythm abnormalities. Doing too much exercise without prior conditioning also increases the risk of injuries to muscles and joints. Damage to muscles due to overexertion is often seen in new military recruits (see Figure 12.5.7). Too much exercise in females may cause amenorrhea, which is a cessation of menstrual periods. When this occurs, it generally indicates that a woman is pushing her body too hard.

Many people develop delayed onset muscle soreness (DOMS), which is pain or discomfort in muscles that is felt one to three days after exercising, and generally subsides two or three days later. DOMS was once thought to be caused by the buildup of lactic acid in the muscles. Lactic acid is a product of anaerobic respiration in muscle tissues. However, lactic acid disperses fairly rapidly, so it is unlikely to explain pain experienced several days after exercise. The current theory is that DOMS is caused by tiny tears in muscle fibres, which occur when muscles are used at too high a level of intensity.

Most people know that exercise is important for good health, and it’s easy to find endless advice about exercise programs and fitness plans. What is not so easy to find is the motivation to start exercising — and to stick with it. This is the main reason why so many people fail to get regular exercise. Practical concerns like a busy schedule and bad weather can certainly make exercising more of a challenge, but the biggest barriers to adopting a regular exercise routine are mental. If you want to exercise but find yourself making excuses or getting discouraged and giving up, here are some tips that may help you get started and stay moving:

• Avoid an all-or-nothing point of view. Don’t think you need to spend hours sweating at the gym or training for a marathon to get healthy. Even a little bit of exercise is better than nothing at all. Start out with ten or 15 minutes of moderate activity each day. Taking a walk around your neighborhood is a great way to begin! From there, gradually increase the amount of time until you are exercising to at least 30 minutes a day, five days a week.  Make it a routine.
• Be kind to yourself, and reinforce positive behaviors with rewards. Don’t be down on yourself because you are overweight or out of shape. Don’t beat yourself up because of a supposed lack of willpower. Instead, look at any past failures as opportunities to learn and do better. When you do achieve even small exercise goals, treat yourself to something special. Did you just complete your first workout? Reward yourself with a relaxing bath or other treat.
• Don’t make excuses for not exercising. Common complaints include being too busy or tired or not athletic enough. Such excuses are not valid reasons to avoid exercising, and they will sabotage any plans to improve your fitness. If you can’t find a 30-minute period to work out, try to find ten minutes, three times a day. If you’re feeling tired, know that exercise can actually reduce fatigue and boost your energy level. If you feel clumsy and uncoordinated, remind yourself that you don’t need to be athletic to take a walk or engage in vigorous house or yard work.
• Find an activity that you truly enjoy doing. Don’t think you have to lift weights or run on a treadmill to exercise your muscles. If you find such activities boring or unpleasant, you won’t stick with them. Any activity that increases your heart rate and uses large muscles can provide a workout, especially if you’re not in the habit of exercising, so find something you like to do. Do you like to dance? Put on some music and dance up a sweat! Do you enjoy gardening? Get out in the yard and dig up some dirt! Still not interested? Try an activity-based video game, such as Wii or Kinect. You may find it so much fun that it doesn’t seem like exercise until you realize you’ve worked up a sweat.
• Make yourself accountable. Tell friends and family members that you’re going to start exercising. You’ll be letting them — as well as yourself — down if you don’t follow through. Some people find that keeping an exercise log to track their progress is a good way to be accountable and stick to an exercise program. Perhaps the best way to keep at it is to find an exercise partner. If you’ve got someone waiting to exercise with you, you will be less likely to make excuses for not exercising.
• Add more physical activity to your daily life. You don’t need to follow a structured exercise program to increase your activity level. Do your house or yard work briskly for a workout. Park your car further than necessary from work or the mall, and walk the extra distance. If you live close enough, leave the car at home and walk to and from your destination. Rather than taking elevators or escalators, walk up and down stairs. When you take breaks at work, take a walk instead of sitting. Every time a commercial comes on while you’re watching TV, take a quick exercise break — run in place or do some curls with hand weights.

 

Attributions

Figure 12.5.1

stroller fit by Serge Melki from Indianapolis, USA on Wikimedia Commons is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0) license.

Figure 12.5.2

Children kayaking young sport by Hagerty Ryan, USFWS on Pixnio is used under a public domain (CC0) Certification (https://creativecommons.org/licenses/publicdomain/).

Figure 12.5.3

Bicep curls [photo] by Senior Airman Jarrod Grammel from U.S. Moody Air Force Base is released into the public domain (https://en.wikipedia.org/wiki/Public_domain).

Figure 12.5.4

Flexibility exercise by carl-barcelo-nqUHQkuVj3c [photo] by Carl Barcelo on Unsplash is used under the Unsplash License (https://unsplash.com/license).

Figure 12.5.5

Canadian women’s double scull silver Rio 2016 by Gerhard Pratt on Flickr is used under a CC BY-NC 2.0 (https://creativecommons.org/licenses/by-nc/2.0/) license.

Figure 12.5.6

Toronto Marathon 2012 by Marc Roberts on Flickr is used under a CC BY-NC-SA 2.0 (https://creativecommons.org/licenses/by-nc-sa/2.0/) license.

Figure 12.5.7

Muscle damage in military recruits by Lance Cpl. Bridget M. Keane from the United States Marine Corps Recruit Depot is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

References

Elwood, P., Galante, J., Pickering, J., Palmer, S., Bayer, A., Ben-Shlomo, Y., Longley, M., & Gallacher, J. (2013). Healthy lifestyles reduce the incidence of chronic diseases and dementia: evidence from the Caerphilly cohort study. PloS one, 8(12), e81877. https://doi.org/10.1371/journal.pone.0081877

Mayo Clinic Staff. (n.d.). Amenorrhea [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/amenorrhea/symptoms-causes/syc-20369299#

Mayo Clinic Staff. (n.d.). Coronary artery disease [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/coronary-artery-disease/symptoms-causes/syc-20350613

TED-Ed. (2016, June 28). How playing sports benefits your body ... and your brain - Leah Lagos and Jaspal Ricky Singh. YouTube. https://www.youtube.com/watch?v=hmFQqjMF_f0&feature=youtu.be

TED-Ed. (2019, April 18). The surprising reason our muscles get tired - Christian Moro. YouTube. https://www.youtube.com/watch?v=rLsimrBoYXc&feature=youtu.be

TED-Ed. (2015, November 3). What makes muscles grow? - Jeffrey Siegel. YouTube https://www.youtube.com/watch?v=2tM1LFFxeKg&feature=youtu.be

TED. (2014, November 14). Why some people find exercise harder than others | Emily Balcetis, YouTube. https://www.youtube.com/watch?v=QeIrdqU0o9s&feature=youtu.be

Wikipedia contributors. (2020, August 1). Delayed onset muscle soreness. In Wikipedia. https://en.wikipedia.org/w/index.php?title=Delayed_onset_muscle_soreness&oldid=970682631

 

 

One of two main divisions of the nervous system that includes the brain and spinal cord.

Created by CK-12 Foundation/Adapted by Christine Miller

Figure 16.3.1 The surprising uses of pee.

What do gun powder, leather, fabric dyes and laundry service have in common?  This may be surprising, but they all historically involved urine.  One of the main components in gun powder, potassium nitrate, was difficult to come by pre-1900s, so ingenious gun-owners would evaporate urine to concentrate the nitrates it contains.  The ammonium in urine was excellent in breaking down tissues, making it a prime candidate for softening leathers and removing stains in laundry.  Ammonia in urine also helps dyes penetrate fabrics, so it was used to make colours stay brighter for longer.

The actual human urinary system, also known as the renal system, is shown in Figure 16.3.2. The system consists of the kidneys, ureters, bladder, and urethra. The main function of the urinary system is to eliminate the waste products of metabolism from the body by forming and excreting urine. Typically, between one and two litres of urine are produced every day in a healthy individual.

The urinary system is all about urine. It includes organs that form urine, and also those that transport, store, or excrete urine.

Kidneys

Urine is formed by the kidneys, which filter many substances out of the blood, allow the blood to reabsorb needed materials, and use the remaining materials to form urine. The human body normally has two paired kidneys, although it is possible to get by quite well with just one. As you can see in Figure 16.3.3, each kidney is well supplied with blood vessels by a major artery and vein. Blood to be filtered enters the kidney through the renal artery, and the filtered blood leaves the kidney through the renal vein. The kidney itself is wrapped in a fibrous capsule, and consists of a thin outer layer called the cortex, and a thicker inner layer called the medulla.

Blood is filtered and urine is formed by tiny filtering units called nephrons. Each kidney contains at least a million nephrons, and each nephron spans the cortex and medulla layers of the kidney. After urine forms in the nephrons, it flows through a system of converging collecting ducts. The collecting ducts join together to form minor calyces (or chambers) that join together to form major calyces (see Figure 16.3.3 above). Ultimately, the major calyces join the renal pelvis, which is the funnel-like end of the ureter where it enters the kidney.

Ureters, Bladder, Urethra

After urine forms in the kidneys, it is transported through the ureters (one per kidney) via peristalsis to the sac-like urinary bladder, which stores the urine until urination. During urination, the urine is released from the bladder and transported by the urethra to be excreted outside the body through the external urethral opening.

Waste products removed from the body with the formation and elimination of urine include many water-soluble metabolic products. The main waste products are urea — a by-product of protein catabolism — and uric acid, a by-product of nucleic acid catabolism. Excess water and mineral ions are also eliminated in urine.

Besides the elimination of waste products such as these, the urinary system has several other vital functions. These include:

• Maintaining homeostasis of mineral ions in extracellular fluid: These ions are either excreted in urine or returned to the blood as needed to maintain the proper balance.
• Maintaining homeostasis of blood pH: When pH is too low (blood is too acidic), for example, the kidneys excrete less bicarbonate (which is basic) in urine. When pH is too high (blood is too basic), the opposite occurs, and more bicarbonate is excreted in urine.
• Maintaining homeostasis of extracellular fluids, including the blood volume, which helps maintain blood pressure: The kidneys control fluid volume and blood pressure by excreting more or less salt and water in urine.

The formation of urine must be closely regulated to maintain body-wide homeostasis. Several endocrine hormones help control this function of the urinary system, including antidiuretic hormone, parathyroid hormone, and aldosterone.

• Antidiuretic hormone (ADH), also called vasopressin, is secreted by the posterior pituitary gland. One of its main roles is conserving body water. It is released when the body is dehydrated, and it causes the kidneys to excrete less water in urine.
• Parathyroid hormone is secreted by the parathyroid glands. It works to regulate the balance of mineral ions in the body via its effects on several organs, including the kidneys. Parathyroid hormone stimulates the kidneys to excrete less calcium and more phosphorus in urine.
• Aldosterone is secreted by the cortex of the adrenal glands, which rest atop the kidneys, as shown in Figure 16.3.4. Through its effect on the kidneys, it plays a central role in regulating blood pressure. It causes the kidneys to excrete less sodium and water in urine.

Once urine forms, it is excreted from the body in the process of urination, also sometimes referred to as micturition. This process is controlled by both the autonomic and the somatic nervous systems. As the bladder fills with urine, it causes the autonomic nervous system to signal smooth muscle in the bladder wall to contract (as shown in Figure 16.3.5), and the sphincter between the bladder and urethra to relax and open. This forces urine out of the bladder and through the urethra. Another sphincter at the distal end of the urethra is under voluntary control. When it relaxes under the influence of the somatic nervous system, it allows urine to leave the body through the external urethral opening.

Figure 16.3.1

• File:Pyrodex powder ffg.jpg by Hustvedt on Wikimedia Commons is used under a CC BY SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0/deed.en).
• Brown leather satchel bag by Álvaro Serrano on Unsplash is used under the Unsplash Licence (https://unsplash.com/license).
• Laundry basket by Andy Fitzsimon on Unsplash is used under the Unsplash Licence (https://unsplash.com/license).
• Tags: Wool Skeins Natural Dyed Colorful Himalayan Weavers by  on Pixabay is used under the Pixabay License (https://pixabay.com/service/license/).

Figure 16.3.2

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 16.3.3

2610_The_Kidney by OpenStax College on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 16.3.4

Adrenal glands on Kidney  by Alan Hoofring (Illustrator)/ NCI Visuals Online is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

Figure 16.3.5

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

References

Alexandria Doody. (2016, March 29). Maple syrup urine disease. YouTube. https://www.youtube.com/watch?v=pyMcTUQYMQw&feature=youtu.be

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 25.8 Left kidney [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

FuseSchool. (2017, June 19). The urinary system - An introduction | Physiology | Biology | FuseSchool. YouTube. https://www.youtube.com/watch?v=dxecGD0m0Xc&feature=youtu.be

Gross Science. (2015, September 15). Three ways pee could change the world. YouTube. https://www.youtube.com/watch?v=xt1Tj5eeS0k&feature=youtu.be

Seeker. (2016, January 16). How accurate are drug tests? YouTube. https://www.youtube.com/watch?v=3z-xjfdJWAI&feature=youtu.be

 

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

A long extension of the cell body of a neuron that transmits nerve impulses to other cells.

Created by: CK-12/Adapted by Christine Miller

Jumping for Joy!

The people in Figure 6.2.1 illustrate some of the great phenotypic variation displayed in modern Homo sapiens. The lighter-skinned men in the photo are Euro-American tourists in Kenya (East Africa). The darker-skinned men are native Kenyans who belong to a tribal group named the Maasai. These men come from populations on different continents on opposite sides of the globe. Their populations have unique histories, environments, and cultures. Besides differences in skin colour, the men have different hair and eye colours, facial features, and body builds. Based on such obvious physical differences, you might think that our species is characterized by a high degree of genetic variation. In fact, there is much less genetic variation in the human species than there is in many other mammalian species, including our closest relatives — the chimpanzees.

No two human individuals are genetically identical unless they are monozygotic (identical) twins. Between any two people, DNA differs, on average, at about one in one thousand nucleotide base pairs. We each have a total of about three billion base pairs, so any two people differ by an average of about three million base pairs. That may sound like a lot, but it's only 0.1% of our total genetic makeup. This means that two people chosen at random are likely to be 99.9 per cent identical genetically, no matter where in the world they come from.

At an individual level, most human genetic variation is not very important biologically, because it has no apparent adaptive significance. It neither enhances nor detracts from individual fitness. Only a small percentage of DNA variations actually occur in coding regions of DNA — which are sequences that are translated into proteins — or in regulatory regions, which are sequences that control gene expression. Differences that occur in other regions of DNA have no impact on phenotype. Even variations in coding regions of DNA may or may not affect phenotype. Some DNA variations may alter the amino acid sequence of a protein, but not affect how the protein functions. Other DNA variations do not even change the amino acid sequence of the encoded protein.

At a population level, genetic variation is crucial if evolution is to occur. Genetically-based differences in fitness among individuals are the key to evolution by natural selection. Without genetic variation within populations, there can be no differential fitness by genotype, and natural selection cannot occur.

Patterns of Human Genetic Variation

Data comparing DNA sequences from around the world show that only about ten per cent of our total genetic variation occurs between people from different continents, like the American tourists and African Maasai pictured in Figure 6.1.1. The other 90 per cent of genetic variation occurs between people within continental populations, such as between North Americans or between Africans. Within any human population, many genes have two or more normal alleles that contribute to genetic differences among individuals. The case in which a gene has two or more alleles in a population at frequencies greater than one per cent is called a polymorphism. A single nucleotide polymorphism (SNP) involves variation in just one nucleotide in a DNA sequence. SNPs account for most of our genetic differences. Other types of variations (such as deletions and insertions of nucleotides in DNA sequences) account for a much smaller proportion of our overall genetic variation.

Different populations may have different allele frequencies for polymorphic genes. However, the distribution of allele frequencies in different populations around the world tends not to be discrete or distinct. Instead, the pattern is more often one of gradual geographic variations, or clines, in allele frequencies. You can see an example of a clinal distribution of allele frequencies in the map (Figure 6.2.2) below. Clinal distributions like this may be a reflection of natural selection pressures varying continuously over geographic space, or they may reflect a combination of genetic drift and gene flow of neutral alleles.

The reason for the different population frequencies for the Duffy antigen appears to be natural selection. People who lack the Duffy antigen are relatively resistant to malaria, which is one of the oldest and most devastating human diseases. Malaria has been a persistent and widespread disease in sub-Saharan Africa for tens of thousands of years. DNA analyses suggest that the allele associated with lack of the Duffy antigen evolved at least twice in Africa and was strongly selected for, causing it to increase in frequency. The Duffy gene is just one of many genes that have polymorphic alleles, because one of the alleles protects against malaria. In fact, a greater number of known genetic polymorphisms may be attributed to selection because of malaria than any other single selective agent.

Factors Influencing the Level of Human Genetic Variation

The age and size of a population increases the genetic variation within that population. You would expect an older, larger population to have more genetic variation. The older a population is, the longer it has been accumulating mutations. The larger a population is, the more people there are in which mutations can occur. Anatomically modern humans evolved less than a quarter million years ago, which is a relatively short period of time for mutations to accumulate. Our population was also quite small at some point in the past, perhaps consisting of no more than ten thousand adults, which reduced genetic variation even more. These factors explain why humans are relatively homogeneous genetically as a species.

Knowledge of genetic variation can help us understand our similarities and differences, our origins, and our evolutionary past. It can also help us understand human diseases and — hopefully — find new ways to treat them.

Human Origins

The data on human genetic variation generally supports the out-of-Africa hypothesis for human origins. According to this hypothesis, the common ancestor of all modern humans evolved in Africa around 200 thousand years ago. Then, starting no later than about 60 thousand years ago, part of the African population left Africa and migrated to Europe and Asia. As the migrants spread throughout the Old World, they replaced (and/or absorbed) the populations of archaic humans they encountered.

Most studies of human genetic variation find there is greater genetic diversity in African than non-African populations. This is consistent with the older age of the African population proposed by the out-of-Africa hypothesis. In addition, most of the genetic variation in non-African populations is a subset of the variation in African populations. This is consistent with the idea that part of the African population left Africa much later and migrated to other places in the Old World.

Recent comparisons of modern human and archaic human (including Neanderthal and Denisovan) DNA show that interbreeding occurred between their populations, but to differing degrees. The result of new DNA sequences entering a population’s gene pool through interbreeding is called admixture. There is greater admixture with archaic humans in modern European, Asian, and Oceanic populations than in modern African populations. Populations with the greatest admixture are those in Melanesia. About eight per cent of their DNA came from archaic Denisovans in East Asia.

Human Population History

Patterns of human genetic variation can be used to reconstruct population history. That history is literally recorded in our DNA. Any major population event (such as a significant reduction in population size or a high rate of migration) leaves a mark on a population’s genetic variation.

• Going through a dramatic size reduction decreases intra-population genetic variation (variation occurring within a population). As a case in point, DNA analyses suggest that there may have been drastic size reductions in the human populations that colonized the New World between 15 thousand and 20 thousand years ago. There were also size reductions in the human populations that first left Africa at least 60 thousand years ago, which helps explain the lower genetic diversity of modern non-African populations.
• A high rate of migration between populations may lead to gene flow, and this changes genetic variation in two ways. Gene flow decreases inter-population genetic variation (variation occurring between populations), while it increases intra-population variation. Gene flow — primarily between nearby populations — may contribute to the formation of clines in allele frequencies, as on the map in Figure 6.2.2.

Human Genetic Variation and Disease

An important benefit of studying human genetic variation is that we can learn more about the genetic basis of human diseases. The more we understand the causes of diseases, the more likely it is that we will be able to find effective treatments and cures for them.

Some disorders are caused by mutations in a single gene. Most of these disorders are generally rare, but some of them occur at significantly higher frequencies in certain populations. For example, Ellis-van Creveld syndrome has an unusually high frequency in Pennsylvania Amish populations, and Tay-Sachs disease has a relatively high frequency in Ashkenazi Jewish populations. Albinism is another single-gene disorder that has a variable frequency. In North America and Europe, rates of albinism are approximately 1:18,000. In Africa, in contrast, the rates range from 1:5,000 to 1:15,000. Some African populations have estimated albinism rates as high as 1:1000. The photo below (Figure 6.2.3) shows an African albino man from Mali, where there is a relatively high rate of albinism. High population-specific frequencies of single-gene disorders like these may be attributable to a variety of factors, such as small founding populations and a relative lack of gene flow.

 

Attributions

Figure 6.2.1

Maasai_men_and_tourists_jumping by Christopher Michel on Wikimedia Commons is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/deed.en) (license.

Figure 6.2.2

Geospatial_distribution_of_SNP_rs1426654-A_allele by Basu Mallick C, Iliescu FM, Möls M, Hill S, Tamang R, Chaubey G, et al. on Wikimedia Commons is used under a  CC BY 2.5 (https://creativecommons.org/licenses/by/2.5/deed.en) license.

Figure 6.2.3

Mali_Salif_Keita2_400 [cropped] by unknown from The Department of State, Washington, DC. on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

References

Basu Mallick C., Iliescu, F.M., Möls, M., Hill, S., Tamang, R., Chaubey, G., et al. (2013). The light skin allele of SLC24A5 in South Asians and Europeans shares identity by descent: Figure 2. Isofrequency map illustrating the geospatial distribution of SNP rs1426654-A allele across the world. PLoS Genetics, 9(11): e1003912. doi:10.1371/journal.pgen.1003912 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003912

HealthLinkBC. (2019, November 5). Health topics: Malaria [online article]. BC Government (gov.bc.ca). https://www.healthlinkbc.ca/health-topics/hw119119

Mayo Clinic Staff. (n.d.). Albinism [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/albinism/symptoms-causes/syc-20369184

Mayo Clinic Staff. (n.d.). Heart disease [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/heart-disease/symptoms-causes/syc-20353118

Mayo Clinic Staff. (n.d.). HIV/AIDS [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/hiv-aids/symptoms-causes/syc-20373524

Mayo Clinic Staff. (n.d.). Type 2 diabetes [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/syc-20351193

National Geographic. (2013, March 13). The journey of your past | National Geographic. YouTube. https://www.youtube.com/watch?v=RGtaq3PiIoU&feature=youtu.be

National Institutes of Health/ National Library of Medicine. (n.d.). Genes: CCR5 gene - C-C motif chemokine receptor 5 [online article]. US Government. https://ghr.nlm.nih.gov/gene/CCR5

National Organization for Rare Disorders (NORD). (2012). Ellis Van Creveld syndrome [online article]. RareDiseases.org. https://rarediseases.org/rare-diseases/ellis-van-creveld-syndrome/

National Organization for Rare Disorders (NORD). (2017). Tay Sachs disease [online article]. RareDiseases.org. https://rarediseases.org/rare-diseases/tay-sachs-disease/

Seeker. (2015, July 25). Why are some people albino?. YouTube. https://www.youtube.com/watch?v=cHRM2S_fBOk&feature=youtu.be

TED. (2011, August 30). Svante Pääbo: DNA clues to our inner neanderthal. YouTube. https://www.youtube.com/watch?v=kU0ei9ApmsY&feature=youtu.be

Wikipedia contributors. (2020, June 18). Melanesia. In Wikipedia. https://en.wikipedia.org/w/index.php?title=Melanesia&oldid=963224885

Wikipedia contributors. (2020, June 4). Old world. In Wikipedia. https://en.wikipedia.org/w/index.php?title=Old_World&oldid=960713597

 

 

 

Created by CK-12 Foundation/Adapted by Christine Miller

Does the organism in Figure 17.2.1 look like a space alien? A scary creature from a nightmare? In fact, it’s a 1-cm long worm in the genus Schistosoma. It may invade and take up residence in the human body, causing a very serious illness known as schistosomiasis. The worm gains access to the human body while it is in a microscopic life stage. It enters through a hair follicle when the skin comes into contact with contaminated water. The worm then grows and matures inside the human organism, causing disease.

The Schistosoma worm has a parasitic relationship with humans. In this type of relationship, one organism, called the parasite, lives on or in another organism, called the host. The parasite always benefits from the relationship, and the host is always harmed. The human host of the Schistosoma worm is clearly harmed by the parasite when it invades the host’s tissues. The urinary tract or intestines may be infected, and signs and symptoms may include abdominal pain, diarrhea, bloody stool, or blood in the urine. Those who have been infected for a long time may experience liver damage, kidney failure, infertility, or bladder cancer. In children, Schistosoma infection may cause poor growth and difficulty learning.

Like the Schistosoma worm, many other organisms can make us sick if they manage to enter our body. Any such agent that can cause disease is called a pathogen. Most pathogens are microorganisms, although some — such as the Schistosoma worm — are much larger. In addition to worms, common types of pathogens of human hosts include bacteria, viruses, fungi, and single-celled organisms called protists. You can see examples of each of these types of pathogens in Table 17.1.1. Fortunately for us, our immune system is able to keep most potential pathogens out of the body, or quickly destroy them if they do manage to get in. When you read this chapter, you’ll learn how your immune system usually keeps you safe from harm — including from scary creatures like the Schistosoma worm!

Table 17.1.1: Types of Disease-Causing Pathogens

Type of Pathogen		Description	Disease Caused
Bacteria: Example shown: Escherichia coli		Single celled organisms without a nucleus	Strep throat, staph infections, tuberculosis, food poisoning, tetanus, pneumonia, syphillis
Viruses: Example shown: Herpes simplex		Non-living particles that reproduce by taking over living cells	Common cold, flu, genital herpes, cold sores, measles, AIDS, genital warts, chicken pox, small pox
Fungi: Example shown: Death cap mushroom		Simple organisms, including mushrooms and yeast, that grow as single cells or thread-like filaments	Ringworm, athletes foot, tineas, candidias, histoplasmomis, mushroom poisoning
Protozoa: Example shown: Giardia lamblia		Single celled organisms with a nucleus	Malaria, "traveller's diarrhea", giardiasis, typano somiasis ("sleeping sickness")

What is the Immune System?

The immune systemno post is a host defense system. It comprises many biological structures —ranging from individual leukocytes to entire organs — as well as many complex biological processes. The function of the immune system is to protect the host from pathogens and other causes of disease, such as tumor (cancer) cells. To function properly, the immune system must be able to detect a wide variety of pathogens. It also must be able to distinguish the cells of pathogens from the host’s own cells, and also to distinguish cancerous or damaged host cells from healthy cells. In humans and most other vertebrates, the immune system consists of layered defenses that have increasing specificity for particular pathogens or tumor cells. The layered defenses of the human immune system are usually classified into two subsystems, called the innate immune system and the adaptive immune system.

Innate Immune System

The innate immune system (sometimes referred to as "non-specific defense") provides very quick, but non-specific responses to pathogens. It responds the same way regardless of the type of pathogen that is attacking the host. It includes barriers — such as the skin and mucous membranes — that normally keep pathogens out of the body. It also includes general responses to pathogens that manage to breach these barriers, including chemicals and cells that attack the pathogens inside the human host. Certain leukocytes (white blood cells), for example, engulf and destroy pathogens they encounter in the process called phagocytosis, which is illustrated in Figure 17.2.2. Exposure to pathogens leads to an immediate maximal response from the innate immune system.

Adaptive Immune System

The adaptive immune system is activated if pathogens successfully enter the body and manage to evade the general defenses of the innate immune system. An adaptive response is specific to the particular type of pathogen that has invaded the body, or to cancerous cells. It takes longer to launch a specific attack, but once it is underway, its specificity makes it very effective. An adaptive response also usually leads to immunity. This is a state of resistance to a specific pathogen, due to the adaptive immune system's ability to “remember” the pathogen and immediately mount a strong attack tailored to that particular pathogen if it invades again in the future.

Both innate and adaptive immune responses depend on the immune system's ability to distinguish between self- and non-self molecules. Self molecules are those components of an organism’s body that can be distinguished from foreign substances by the immune system. Virtually all body cells have surface proteins that are part of a complex called major histocompatibility complex (MHC). These proteins are one way the immune system recognizes body cells as self. Non-self proteins, in contrast, are recognized as foreign, because they are different from self proteins.

Antigens and Antibodies

Many non-self molecules comprise a class of compounds called antigens. Antigens, which are usually proteins, bind to specific receptors on immune system cells and elicit an adaptive immune response. Some adaptive immune system cells (B cells) respond to foreign antigens by producing antibodies. An antibody is a molecule that precisely matches and binds to a specific antigen. This may target the antigen (and the pathogen displaying it) for destruction by other immune cells.

Antigens on the surface of pathogens are how the adaptive immune system recognizes specific pathogens. Antigen specificity allows for the generation of responses tailored to the specific pathogen. It is also how the adaptive immune system ”remembers” the same pathogen in the future.

Immune Surveillance

Another important role of the immune system is to identify and eliminate tumor cells. This is called immune surveillance. The transformed cells of tumors express antigens that are not found on normal body cells. The main response of the immune system to tumor cells is to destroy them. This is carried out primarily by aptly-named killer T cells of the adaptive immune system.

The lymphatic system is a human organ system that is a vital part of the adaptive immune system. It is also part of the cardiovascular system and plays a major role in the digestive system (see section 17.3 Lymphatic System). The major structures of the lymphatic system are shown in Figure 17.2.3 .

The lymphatic system consists of several lymphatic organs and a body-wide network of lymphatic vessels that transport the fluid called lymph. Lymph is essentially blood plasma that has leaked from capillaries into tissue spaces. It includes many leukocytes, especially lymphocytes, which are the major cells of the lymphatic system. Like other leukocytes, lymphocytes defend the body. There are several different types of lymphocytes that fight pathogens or cancer cells as part of the adaptive immune system.

Major lymphatic organs include the thymus and bone marrow. Their function is to form and/or mature lymphocytes. Other lymphatic organs include the spleen, tonsils, and lymph nodes, which are small clumps of lymphoid tissue clustered along lymphatic vessels. These other lymphatic organs harbor mature lymphocytes and filter lymph. They are sites where pathogens collect, and adaptive immune responses generally begin.

The brain and spinal cord are normally protected from pathogens in the blood by the selectively permeable blood-brain and blood-spinal cord barriers. These barriers are part of the neuroimmune system. The neuroimmune system has traditionally been considered distinct from the rest of the immune system, which is called the peripheral immune system — although that view may be changing. Unlike the peripheral system, in which leukocytes are the main cells, the main cells of the neuroimmune system are thought to be nervous system cells called neuroglia. These cells can recognize and respond to pathogens, debris, and other potential dangers. Types of neuroglia involved in neuroimmune responses include microglial cells and astrocytes.

• Microglial cells are among the most prominent types of neuroglia in the brain. One of their main functions is to phagocytize cellular debris that remains when neurons die. Microglial cells also “prune” obsolete synapses between neurons.
• Astrocytes are neuroglia that have a different immune function. They allow certain immune cells from the peripheral immune system to cross into the brain via the blood-brain barrier to target both pathogens and damaged nervous tissue.

“They’ll have to rewrite the textbooks!”

That sort of response to a scientific discovery is sure to attract media attention, and it did. It’s what Kevin Lee, a neuroscientist at the University of Virginia, said in 2016 when his colleagues told him they had discovered human anatomical structures that had never before been detected. The structures were tiny lymphatic vessels in the meningeal layers surrounding the brain.

How these lymphatic vessels could have gone unnoticed when all human body systems have been studied so completely is amazing in its own right. The suggested implications of the discovery are equally amazing:

• The presence of these lymphatic vessels means that the brain is directly connected to the peripheral immune system, presumably allowing a close association between the human brain and human pathogens. This suggests an entirely new avenue by which humans and their pathogens may have influenced each other’s evolution. The researchers speculate that our pathogens even may have influenced the evolution of our social behaviors.
• The researchers think there will also be many medical applications of their discovery. For example, the newly discovered lymphatic vessels may play a major role in neurological diseases that have an immune component, such as multiple sclerosis. The discovery might also affect how conditions such as autism spectrum disorders and schizophrenia are treated.

Attributions

Figure 17.1.1

Schistosome Parasite by Bruce Wetzel and Harry Schaefer (Photographers) from the National Cancer Institute, Visuals online is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

Figure 17.1.2

Phagocytosis by Rlawson at en.wikibooks on Wikimedia Commons is used under a CC BY ­SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0/deed.en) license. (Transferred from en.wikibooks to Commons by User:Adrignola.)

Figure 17.1.3

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

 

Table 17.1.1 

• EscherichiaColi NIAID [photo] by Rocky Mountain Laboratories,  NIH National Institute of Allergy and Infectious Diseases (NIAID) on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).
• Herpes simplex virus TEM B82-0474 lores by Dr. Erskine Palmer/ CDC Public Health Image Library (PHIL) on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).
• Red death cap mushroom by Rosendahl on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain). (Transferred from Pixnio by Fæ.)
• Scanning electron micrograph (SEM) of Giardia lamblia by Janice Haney Carr/ CDC, Public Health Image Library (PHIL) Photo ID# 8698 is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

References

Barney, J. (2016, March 21). They’ll have to rewrite the textbooks [online article]. Illimitable - Discovery. UVA Today/ University of Virginia. https://news.virginia.edu/illimitable/discovery/theyll-have-rewrite-textbooks

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

Handwritten Tutorials. (2011, October 25). Overview of the immune system. YouTube. https://www.youtube.com/watch?v=Nw27_jMWw10&feature=youtu.be

ImmiflexImmuneSystem. (2013). Neutrophil phagocytosis - White blood cell eats staphylococcus aureus bacteria. YouTube. https://www.youtube.com/watch?v=Z_mXDvZQ6dU

Kurzgesagt – In a Nutshell. (2016, March 16). The antibiotic apocalypse explained. YouTube. https://www.youtube.com/watch?v=xZbcwi7SfZE&feature=youtu.be

Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., Derecki, N. C., Castle, D., Mandell, J. W., Lee, K. S., Harris, T. H., & Kipnis, J. (2015). Structural and functional features of central nervous system lymphatic vessels. Nature, 523(7560), 337–341. https://doi.org/10.1038/nature14432

Mayo Clinic Staff. (n.d.). Autism spectrum disorder [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/autism-spectrum-disorder/symptoms-causes/syc-20352928

Mayo Clinic Staff. (n.d.). Multiple sclerosis [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269

Mayo Clinic Staff. (n.d.). Schizophrenia [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/schizophrenia/symptoms-causes/syc-20354443

TED-Ed. (2016, April 19). The surprising reason you feel awful when you're sick - Marco A. Sotomayor. YouTube. https://www.youtube.com/watch?v=gVdY9KXF_Sg&feature=youtu.be

 

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

 

Created by CK-12 Foundation/Adapted by Christine Miller

It’s just a paper cut, but the break in your skin could provide an easy way for pathogens to enter your body. If bacteria were to enter through the cut and infect the wound, your innate immune system would quickly respond with a dizzying array of general defenses.

The innate immune system is a subset of the human immune system that produces rapid, but non-specific responses to pathogens. Innate responses are generic, rather than tailored to a particular pathogen. The innate system responds in the same general way to every pathogen it encounters. Although the innate immune system provides immediate and rapid defenses against pathogens, it does not confer long-lasting immunity to them. In most organisms, the innate immune system is the dominant system of host defense. Other than most vertebrates (including humans), the innate immune system is the only system of host defense.

In humans, the innate immune system includes surface barriers, inflammation, the complement system, and a variety of cellular responses. Surface barriers of various types generally keep most pathogens out of the body. If these barriers fail, then other innate defenses are triggered. The triggering event is usually the identification of pathogens by pattern-recognition receptors on cells of the innate immune system. These receptors recognize molecules that are broadly shared by pathogens, but distinguishable from host molecules. Alternatively, the other innate defenses may be triggered when damaged, injured, or stressed cells send out alarm signals, many of which are recognized by the same receptors as those that recognize pathogens.

The body’s first line of defense consists of three different types of barriers that keep most pathogens out of body tissues. The types of barriers are mechanical, chemical, and biological barriers.

Mechanical Barriers

Mechanical barriers are the first line of defense against pathogens, and they physically block pathogens from entering the body. The skin is the most important mechanical barrier. In fact, it is the single most important defense the body has. The outer layer of skin — the epidermis — is tough, and very difficult for pathogens to penetrate. It consists of dead cells that are constantly shed from the body surface, a process that helps remove bacteria and other infectious agents that have adhered to the skin. The epidermis also lacks blood vessels and is usually lacking moisture, so it does not provide a suitable environment for most pathogens. Hair — which is an accessory organ of the skin — also helps keep out pathogens. Hairs inside the nose may trap larger pathogens and other particles in the air before they can enter the airways of the respiratory system (see Figure 17.4.2).

Mucous membranes provide a mechanical barrier to pathogens and other particles at body openings. These membranes also line the respiratory, gastrointestinal, urinary, and reproductive tracts. Mucous membranes secrete mucus, which is a slimy and somewhat sticky substance that traps pathogens. Many mucous membranes also have hair-like cilia that sweep mucus and trapped pathogens toward body openings, where they can be removed from the body. When you sneeze or cough, mucus and pathogens are mechanically ejected from the nose and throat, as you can see in Figure 17.4.3.  A sneeze can travel as fast as 160 Km/hr (about 99 mi/hour) and expel as many as 100,000 droplets into the air around you (a good reason to cover your sneezes!). Other mechanical defenses include tears, which wash pathogens from the eyes, and urine, which flushes pathogens out of the urinary tract.

Chemical Barriers

Chemical barriers also protect against infection by pathogens. They destroy pathogens on the outer body surface, at body openings, and on inner body linings. Sweat, mucus, tears, saliva, and breastmilk all contain antimicrobial substances (such as the enzyme lysozyme) that kill pathogens, especially bacteria. Sebaceous glands in the dermis of the skin secrete acids that form a very fine, slightly acidic film on the surface of the skin. This film acts as a barrier to bacteria, viruses, and other potential contaminants that might penetrate the skin. Urine and vaginal secretions are also too acidic for many pathogens to endure. Semen contains zinc — which most pathogens cannot tolerate — as well as defensins, which are antimicrobial proteins that act mainly by disrupting bacterial cell membranes. In the stomach, stomach acid and digestive enzymes called proteases (which break down proteins) kill most of the pathogens that enter the gastrointestinal tract in food or water.

Biological Barriers

Biological barriers are living organisms that help protect the body from pathogens. Trillions of harmless bacteria normally live on the human skin and in the urinary, reproductive, and gastrointestinal tracts. These bacteria use up food and surface space that help prevent pathogenic bacteria from colonizing the body. Some of these harmless bacteria also secrete substances that change the conditions of their environment, making it less hospitable to potentially harmful bacteria. They may release toxins or change the pH, for example. All of these effects of harmless bacteria reduce the chances that pathogenic microorganisms will be able to reach sufficient numbers and cause illness.

If pathogens manage to breach the barriers protecting the body, one of the first active responses of the innate immune system kicks in. This response is inflammation. The main function of inflammation is to establish a physical barrier against the spread of infection. It also eliminates the initial cause of cell injury, clears out dead cells and tissues damaged from the original insult and the inflammatory process, and initiates tissue repair. Inflammation is often a response to infection by pathogens, but there are other possible causes, including burns, frostbite, and exposure to toxins.

The signs and symptoms of inflammation include redness, swelling, warmth, pain, and frequently some loss of function. These symptoms are caused by increased blood flow into infected tissue, and a number of other processes, illustrated in Figure 17.4.4.

Inflammation is triggered by chemicals such as cytokines and histamines,which are released by injured or infected cells, or by immune system cells such as macrophages (described below) that are already present in tissues. These chemicals cause capillaries to dilate and become leaky, increasing blood flow to the infected area and allowing blood to enter the tissues. Pathogen-destroying leukocytes and tissue-repairing proteins migrate into tissue spaces from the bloodstream to attack pathogens and repair their damage. Cytokines also promote chemotaxis, which is migration to the site of infection by pathogen-destroying leukocytes. Some cytokines have anti-viral effects. They may shut down protein synthesis in host cells, which viruses need in order to survive and replicate.

See the video "The inflammatory response" by Neural Academy to learn about inflammatory response in more detail:

https://youtu.be/Fbzb75HA9M8

The inflammatory response, Neural Academy, 2019.

The complement system is a complex biochemical mechanism named for its ability to “complement” the killing of pathogens by antibodies, which are produced as part of an adaptive immune response. The complement system consists of more than two dozen proteins normally found in the blood and synthesized in the liver. The proteins usually circulate as non-functional precursor molecules until activated.

As shown in Figure 17.4.5, when the first protein in the complement series is activated —typically by the binding of an antibody to an antigen on a pathogen — it sets in motion a domino effect. Each component takes its turn in a precise chain of steps known as the complement cascade. The end product is a cylinder that punctures a hole in the pathogen’s cell membrane. This allows fluids and molecules to flow in and out of the cell, which swells and bursts.

Cellular responses of the innate immune system involve a variety of different types of leukocytes. Many of these leukocytes circulate in the blood and act like independent, single-celled organisms, searching out and destroying pathogens in the human host. These and other immune cells of the innate system identify pathogens or debris, and then help to eliminate them in some way. One way is by phagocytosis.

Phagocytosis

Phagocytosis is an important feature of innate immunity that is performed by cells classified as phagocytes. In the process of phagocytosis, phagocytes engulf and digest pathogens or other harmful particles. Phagocytes generally patrol the body searching for pathogens, but they can also be called to specific locations by the release of cytokines when inflammation occurs. Some phagocytes reside permanently in certain tissues.

As shown in Figure 17.4.6, when a pathogen such as a bacterium is encountered by a phagocyte, the phagocyte extends a portion of its plasma membrane, wrapping the membrane around the pathogen until it is enveloped. Once inside the phagocyte, the pathogen becomes enclosed within an intracellular vesicle called a phagosome. The phagosome then fuses with another vesicle called a lysosome, forming a phagolysosome. Digestive enzymes and acids from the lysosome kill and digest the pathogen in the phagolysosome. The final step of phagocytosis is excretion of soluble debris from the destroyed pathogen through exocytosis.

Types of leukocytes that kill pathogens by phagocytosis include neutrophils, macrophages, and dendritic cells. You can see illustrations of these and other leukocytes involved in innate immune responses in Figure 17.4.7.

Neutrophils

Neutrophils are leukocytes that travel throughout the body in the blood. They are usually the first immune cells to arrive at the site of an infection. They are the most numerous types of phagocytes, and they normally make up at least half of the total circulating leukocytes. The bone marrow of a normal healthy adult produces more than 100 billion neutrophils per day. During acute inflammation, more than ten times that many neutrophils may be produced each day. Many neutrophils are needed to fight infections, because after a neutrophil phagocytizes just a few pathogens, it generally dies.

Macrophages

Macrophages are large phagocytic leukocytes that develop from monocytes. Macrophages spend much of their time within the interstitial fluid in body tissues. They are the most efficient phagocytes, and they can phagocytize substantial numbers of pathogens or other cells. Macrophages are also versatile cells that produce a wide array of chemicals — including enzymes, complement proteins, and cytokines — in addition to their phagocytic action. As phagocytes, macrophages act as scavengers that rid tissues of worn-out cells and other debris, as well as pathogens. In addition, macrophages act as antigen-presenting cells that activate the adaptive immune system.

Dendritic Cells

Like macrophages, dendritic cells develop from monocytes. They reside in tissues that have contact with the external environment, so they are located mainly in the skin, nose, lungs, stomach, and intestines. Besides engulfing and digesting pathogens, dendritic cells also act as antigen-presenting cells that trigger adaptive immune responses.

Eosinophils

Eosinophils are non-phagocytic leukocytes that are related to neutrophil. They specialize in defending against parasites. They are very effective in killing large parasites (such as worms) by secreting a range of highly-toxic substances when activated. Eosinophils may become overactive and cause allergies or asthma.

Basophils

Basophils are non-phagocytic leukocytes that are also related to neutrophils. They are the least numerous of all white blood cells. Basophils secrete two types of chemicals that aid in body defenses: histamines and heparin. Histamines are responsible for dilating blood vessels and increasing their permeability in inflammation. Heparin inhibits blood clotting, and also promotes the movement of leukocytes into an area of infection.

Mast Cells

Mast cells are non-phagocytic leukocytes that help initiate inflammation by secreting histamines. In some people, histamines trigger allergic reactions, as well as inflammation. Mast cells may also secrete chemicals that help defend against parasites.

Natural Killer Cells

Natural killer cells are in the subset of leukocytes called lymphocytes, which are produced by the lymphatic system. Natural killer cells destroy cancerous or virus-infected host cells, although they do not directly attack invading pathogens. Natural killer cells recognize these host cells by a condition they exhibit called “missing self.” Cells with missing self have abnormally low levels of cell-surface proteins of the major histocompatibility complex (MHC), which normally identify body cells as self.

Many pathogens have evolved mechanisms that allow them to evade human hosts' innate immune systems. Some of these mechanisms include:

• Invading host cells to replicate so they are “hidden” from the immune system. The bacterium that causes tuberculosis uses this mechanism.
• Forming a protective capsule around themselves to avoid being destroyed by immune system cells. This defense occurs in bacteria, such as Salmonella species.
• Mimicking host cells so the immune system does not recognize them as foreign. Some species of Staphylococcus bacteria use this mechanism.
• Directly killing phagocytes. This ability evolved in several species of bacteria, including the species that causes anthrax.
• Producing molecules that prevent the formation of interferons, which are immune chemicals that fight viruses. Some influenza viruses have this capability.
• Forming complex biofilms that provide protection from the cells and proteins of the immune system. This characterizes some species of bacteria and fungi. You can see an example of a bacterial biofilm on teeth in Figure 17.4.8.

Attributions

Figure 17.4.1

Oww_Papercut_14365 by Laurence Facun on Wikimedia Commons is used under a CC BY 2.0 (https://creativecommons.org/licenses/by/2.0) license.

Figure 17.4.2

hairy-nose by Piotr Siedlecki  on publicdomainpictures.net is used under a CC0 1.0 Universal Public Domain Dedication (http://creativecommons.org/publicdomain/zero/1.0/) license.

Figure 17.4.3

1024px-Sneeze by James Gathany/ CDC Public Health Image library (PHIL) ID# 11162 on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/public_domain).

Figure 17.4.4

OSC_Microbio_17_06_Erythema by CNX OpenStax on Wikimedia Commons is used under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0) license.

Figure 17.4.5

2212_Complement_Cascade_and_Function by OpenStax College on Wikimedia Commons is used under a CC BY 3.0 (https://creativecommons.org/licenses/by/3.0) license.

Figure 17.4.6

512px-Phagocytosis2 by Graham Colm at English Wikipedia on Wikimedia Commons is used under a CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) license.

Figure 17.4.7

Innate_Immune_cells.svg by Fred the Oyster on Wikimedia Commons is in the public domain (https://en.wikipedia.org/wiki/Public_domain).

Figure 17.4.8

1024px-Gingivitis-before-and-after-3 by Onetimeuseaccount on Wikimedia Commons is used under a CC0 1.0 Universal Public Domain Dedication (http://creativecommons.org/publicdomain/zero/1.0/) 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 21.13 Complement cascade and function [digital image].  In Anatomy and Physiology (Section 21.2). OpenStax. https://openstax.org/books/anatomy-and-physiology/pages/21-2-barrier-defenses-and-the-innate-immune-response

Discovery. (2011, October 27). Cough grosser than sneeze? | Curiosity - World's dirtiest man. YouTube. https://www.youtube.com/watch?v=dy1D3d1FBcw&feature=youtu.be

Gross Science. (2017, January 31). Everything you didn't want to know about snot. YouTube. https://www.youtube.com/watch?v=shEPwQPQG4I&feature=youtu.be

Janux. (2015, January 10). Human physiology - Innate immune system. YouTube. https://www.youtube.com/watch?v=sYjtMP67vyk&feature=youtu.be

Mayo Clinic Staff. (n.d.). Anthrax [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/anthrax/symptoms-causes/syc-20356203

Mayo Clinic Staff. (n.d.). Influenza (flu) [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/flu/symptoms-causes/syc-20351719

Mayo Clinic Staff. (n.d.). Salmonella infection [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/salmonella/symptoms-causes/syc-20355329

Mayo Clinic Staff. (n.d.). Staph infection [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/staph-infections/multimedia/staph-infection/img-20008600

Mayo Clinic Staff. (n.d.). Tuberculosis [online article]. MayoClinic.org. https://www.mayoclinic.org/diseases-conditions/tuberculosis/symptoms-causes/syc-20351250

OpenStax. (2016, November 11). Figure 17.23 A typical case of acute inflammation at the site of a skin wound - Erythema [digital image]. In OpenStax, Microbiology (Section 17.5). https://openstax.org/details/books/microbiology?Bookdetails

TED. (2014, October 14). Myriam Sidibe: The simple power of handwashing. YouTube. https://www.youtube.com/watch?v=c64M1tZyWPM&feature=youtu.be

TED-Ed. (2015, November 5). How mucus keeps us healthy - Katharina Ribbeck. YouTube. https://www.youtube.com/watch?v=WW4skW6gucU&feature=youtu.be

A division of the autonomic nervous system that controls digestive functions.

division of the peripheral nervous system that controls involuntary activities