Immune System

Introduction

This chapter discusses several different mechanisms used to defend the body against pathogens and toxic chemicals. The first line of defense consists of barriers that prevent harmful substances from entering the body.
If the barriers become breached and foreign materials enter the body, a number of mechanisms act to prevent them from doing harm. Innate immunity refers to nonspecific mechanisms that are generally effective against a variety of infections. The effectiveness of innate immunity is not enhanced by exposure to infectious agents.
The detection of foreign particles involves the use of receptors. A reaction is triggered when foreign particles bind to a receptor. Receptors used in the innate immune response are able to bind to molecules that are common in pathogens but are not found in the animal's body.
Adaptive immunity refers to  mechanisms that are specific for one type of  infection. Adaptive immunity is generally acquired after exposure to the infecting particles or cells.
Receptors used in adaptive immunity are specific. They often function for a specific type of molecule which may be found only in a specific kind of infection. Due to their specificity, a large variety of these receptors are needed in order to respond to a large number of possible infective agents. When one specific kind of these receptors binds to molecules, the resulting reactions produce many more of the same kind of receptor. Thus, exposure to an infective agent increases the number of receptors capable of binding to that agent.
Innate immunity is found in all animals. Adaptive immunity is found only in vertebrates.

Barriers

The skin and epithelial tissue covering the body's exterior and interior surfaces are the main barrier preventing the entry of foreign organisms and particles. The cells of these surface tissues are linked by tightjunctions which prevents the passage of materials between the cells.
The low pH of skin oils and sweat glands weaken or kill bacteria.
Mucus, produced by mucous membranes, traps microorganisms and other small particles. Cilia lining the respiratory tract sweep mucus and trapped particles to the pharynx where they are swallowed.
The low pH of the stomach kills microorganisms that are swallowed.
Tears wash the eyes.
Saliva helps clean teeth, preventing dental caries.
Urine flow prevents colonization of the urinary tract.
The low pH of the vagina kills or inhibits many kinds of microorganisms. Vaginal secretions move microorganisms out of the reproductive tract.
Lysozyme is found in tears, saliva, and mucus. It inhibits many kinds of bacteria by breaking down their cell walls.
The normal bacterial colonists of the skin, gut, and vagina prevent harmful microorganisms from colonizing the areas.

Innate Immunity

Innate Cellular Responses

A variety of white blood cells (leukocyes) function in both innate and adaptive immunity.

Some leukocytes are phagocytic (capable of phagocytosis). They contain toll-like receptors that are able to recognize certain patterns of molecules typically found in pathogens but not in the host. Pathogens that are identified by this method are then phagocytized.

During phagocytosis, the foreign particle is engulfed by the phagocyte and brought into the cell within a vesicle. The vesicle containing the foreign material then fuses with a lysosome containing digestive enzymes that are capable of destroying the contents of the vesicle. Next, the vesicle containing the remnants of digestion fuses with the plasma membrane, emptying its contents to the outside.

Phagocytes

Neutrophils are found in the blood. They are attracted to damaged or infected tissue by chemical signals.

Macrophages are found in the blood and also  in the tissues.

Dendritic cells are found on surfaces that are exposed to the environment.

Natural Killer Cells

Virus-infected cells may have abnormal proteins on their surface due to their infection. These proteins can be recognized by natural killer cells which kill the infected cell, thus preventing the spread of infection.

Natural killer cells are able to recognize and then kill virus-infected cells and cancer cells because they have fewer MHC (major histocompatability complex) proteins on their surface than normal body cells.

Inflammatory Reaction

The inflammatory reaction is a local response to injury or infection.
Damaged tissue stimulates mast cells to release histamine which causes an increase in blood vessel diameter (vasodilation) and increased permeability of the blood vessels. This brings more blood flow to the area including more infection-fighting leukocytes (white blood cells) such as monocytes and neutrophils.
Inflammation occurs when fluids and infection-fighting cells leak from the blood vessels into the tissues. The swelling and redness associated with inflammation is due to increased blood flow to the area and to fluid leaking from the blood vessels into the tissues.
Macrophages are activated when their toll-like receptors bind to foreign molecules. These activated macrophages release signaling molecules called cytokines which, like histamine, cause vasodilation and increased permeability of the blood vessels.Cytokines released by macrophages attract neutrophils and monocytes to the area. Within the tissues, monocytes differentiate into macrophages.
The toll-like receptors of neutrophils and macrophages enable them to identify foreign material which they phagocytize.
Bacteria may release chemicals that kill leukocytes. In addition, neutrophils are often killed as a result of chemical processes used to kill pathogens after phagocytosis. Pus is a substance that contains a large number of dead leukocytes, particularly neutrophils, and other debris that remains at the infection or damage site.
Some pathogenic organisms are too large to be phagocytized. Instead, these organisms are killed by chemicals released by macrophages, neutrophils, and eosinophils.

The Complement System

The complement system consists of a number of different proteins that help defend the body when they are activated. It is called complement because it enhances (complements) other immune responses such as the inflammatory reaction (an innate response discussed above) and the antibody-mediated response (an adaptive response discussed later).
Compliment proteins function in innate immunity when they are activated by molecules on the surface of microorganisms. Each activated complement protein activates many others so that a large number of active proteins are produced.
Some activated complement proteins form membrane attack complexes which produce holes in bacterial cell membranes. The holes disrupt the osmotic balance by allowing salts and fluids to enter, rupturing the cell.
Activated compliment proteins also stimulate mast cells, promoting the release of histamine and enhancing the inflammation reaction discussed above.

Some Other Important Molecules

Interferons are proteins produced by virus-infected animal cells that stimulate themselves and other nearby cells to produce substances that interfere with viral replication. Interferons may also activate natural killer cells.

Lysozyme is an enzyme capable of breaking down the cell walls of gram-positive bacteria. It is found in sweat, tears, saliva, nasal secretions, and tissue fluids.
Epithelial tissues, along with neutrophils, produce chemical substances called defensins that attach to microbial cell membranes forming pores in the membrane, thus killing the microorganism.

Adaptive Immunity

Antigens

Antigens are usually foreign molecules that have entered the body. The body is able to recognize that they are foreign because it has antigen receptors that are able to bind to specific antigens.

Antigen receptors are able to attach to a portion of the antigen because the shape matches. The portion of the antigen that matches the shape of the receptor is called an epitope.

The body does not produce antigen receptors that bind to its own (self) antigens. Therefore particles that are bound to antigen receptors are foreign.

MHC Proteins

The two kinds of immunity discussed in this section require that the body be able to identify its own cells (self) from foreign particles and foreign cells. When antigens are discovered, they need to be displayed so that other immune cells can be activated and then remove the foreign particles. The lymphocytes involved also need to be able to distinguish which self cells have been infected so that the infected cells can be destroyed.
Body cells contain proteins on their surface called MHC (major histocompatability complex) proteins. Every person has unique MHC proteins. When a body cell is infected, the infected cell will attach antigens from the pathogen to class I MHC proteins and then move the MHC-antigen complex to the surface of the cell. This marks the cell as being infected and certain other lymphocytes that can see the MHC-antigen complex will destroy the infected cell, preventing the infection from spreading.
The class I MHC proteins attached to the cell in the drawing below indicate that it is one of the body's own cells. The antigen fragments attached to the class I MHC proteins indicate that the cell is infected. Antigen fragments which are attached to class I MHC proteins originated from pathogens inside the cell.

Certain cells of the immune system may also encounter antigens that are not inside body cells. These particles are typically phagocytized, digested, and then antigen fragments are attached to class II MHC proteins which are then moved to the surface. Antigens attached to class II MHC proteins communicate that the cell is not infected. It enables the cell to display the antigen to other cells so that they can become activated.
The cell in the drawing below is not infected. The presence of antigen fragments attached to class II MHC proteins indicates that the antigens originated outside of the cell.

In summary, antigens attached to class I MHC proteins indicate that the cell displaying the antigen is infected; the antigen originated inside the cell. Antigens attached to class II MHC proteins indicate that the cell is not infected because the antigen originated outside of the cell; it was phagocytized.

Summary Diagram of Adaptive Immunity

The diagram below might be a helpful reference as you read about adaptive immunity below.

Cell-mediated Immunity and T lymphocytes

Cell mediated immunity involves the use of T lymphocytes (T cells) to fight other body cells that may have become harmful such as virus-infected cells and cancer cells. It also fights single-celled fungi and other parasites, and the cells of an organ transplant.
All lymphocytes are produced in the bone marrow. T lymphocytes move to the thymus to mature. B lymphocytes mature in the bone marrow.
T cells must become activated before they function in immunity. Activated helper T cells are needed to activate cytotoxic T cells, which are used to destroy infected cells and some cancer cells. Activated helper T cells are also needed to activate B lymphocytes needed in antibody-mediated immunity.
T cells contain antigen receptors on their surface and the cells become activated when the antigen receptors bind with antigen/MHC complexes from a host cell. There are millions of different kinds of antigen receptors on the surface of T cells but all of the receptors on the surface of a single T cell are identical; they are all capable of binding with the same antigen/MHC complex. Other T cells have different antigen receptors.
The type of antigen receptor is due to genetics. When a T cell is initially activated, it divides by mitosis to produce a clone of cells, each with identical antigen receptors. T cells with antigen receptors that do not match the antigen will not bind with the antigen and will not be activated or cloned.

Helper T Cells

Helper T cells cannot recognize antigens unless an antigen-presenting cell such as a dendritic cell or a macrophage presents an antigen to them.
The antigen-presenting cell first phagocytizes the antigen (or bacterium, virus, etc.), digests the particles, and moves fragments of the foreign antigens to its surface linked to class II MHC proteins.
Activated helper T cells are produced when the antigen receptors of a T cell attach to antigens displayed on type II MHC proteins of antigen-displaying cells. After activation, they divide to produce a clone of identical helper T cells. These new activated helper T cells are able to activate other T cells and B cells by secreting cytokines.
This process is summarized below:

CD4⁺  T cell  encounters an antigen presenting cell with antigen-MHC type II → clone of T cells → some become helper T cells, others become memory helper T cells → activateB cells and cytotoxic T cells

HIV (the virus that causes AIDS) attacks helper T cells as well as other cells in the immune system. HIV therefore prevents adaptive immunity from becoming activated.

Cytotoxic T Cells

Infected cells contain antigens attached to type I MHC proteins on their surface. Cytotoxic T cells (also called killer T cells) kill these infected cells.
A clone of cytotoxic T cells is produced when a T cell encounters a body cell with matching antigen attached to MHC type 1 protein. Their production also requires the presence of cytokines secreted by helper T cells (discussed earlier). Some of the cloned cells are cytotoxic T cells, others are memory cytotoxic T cells.
Cytotoxic T cells with receptors that recognize the antigen and also the MHC type 1 proteins will release proteins that kill the cell, thus stopping the spread of infection. Some of the proteins released by cytotoxic T cells penetrate the target cell membrane, producing holes in the membrane. Salts and fluid enter through the holes, causing the cell to rupture. Other proteins released by the cytotoxic T cell enter the target cell and stimulate apoptosis.
This process is summarized below:

CD8⁺  T cell  encounters a cell with antigen-type I MHC in the presence of cytokines from helper T cells  → clone of T cells → some become cytotoxic T cells, othters become memory cytotoxic T cells → cytotoxic T cells kill infected cells (cells with with antigen-MHC type I)

Some cancer cells display abnormal antigens in type I MHC proteins and are killed by cytotoxic T cells.

Memory Cells

Some of the cloned helper T cells become memory helper T cells and some of the cloned cytotoxic T cells become memory cytotoxic T cells. These memory cells persist after the infection and are available for activation if the body encounters the same infection in the future.

Antibody-mediated (Humoral) Immunity

Antibodies

Antibodies are similar to antigen receptors except that they are not attached to cells. They are Y-shaped molecules with a constant region and two binding sites that vary from one antibody to the next.
Particles that are bound to antibodies are foreign because, like antigen receptors, the body does not normally produce antibodies that are able to bind to its own antigens.
The following occurs to cells, particles, or molecules that are marked with antibodies:

1. Opsonization- The presence of antibodies bound to antigens enhances phagocytosis.
2. Neutralization- Toxic molecules that are attached to antibodies may not be able to affect cells.
3. Agglutination- Bacteria, viruses, and other particles may agglutinate (clump together) because each antibody is capable of binding to two antigens. If the antigens are chemicals that are dissolved in the body fluids, the clumps of antibody-bound particles will precipitate. Antigens attached to cells will cause the cells to clump together and the clumps are then phagocytized. Agglutination of pathogens can stop the spread of the infection.
4. Activation of the complement system.  Membrane attack complexes form and produce holes in the plasma membranes of bacterial cells, killing the cell.

During our life, we will encounter over 1 million different antigens, so we need at least 1 million different antibodies, each corresponding to a specific antigen. It has been estimated that our bodies are able to produce 100 million different kinds of antibodies.
There are 5 different classes of antibodies (IgA, IgD, IgG, IgH, IgM).
Antibodies are produced by a special kind of B lymphocyte called plasma cells.

Antibody Structure and Diversity

An antibody is composed of two identical light chains of amino acids and two identical heavy chains arranged in the shape of a "Y". Each antibody contains a constant region that does not vary from antibody to antibody and it also contains a variable region that does vary. The antigen binding site is within the variable region. The structure shown below is typical of IgM antibodies and of antigen receptors on B cells. The antigen receptors of T cells have only one antigen binding site.

The human genome contains approximately 20,000 genes but humans have approximately 100,000,000 different antibodies and antigen receptors. This large number of antibodies and receptors is possible due to rearrangements of randomly-selected regions of DNA when lymphocytes mature. 

For example, an immature B lymphocyte contains a large region of DNA that will become the functional gene. When the lymphocyte matures, randomly selected regions from two different areas of this DNA will be reassembled to form the part of the gene that codes for the variable region of the antibody. The two regions are called the V region (red in the diagram below) and the J region (green). The DNA between the V and the J areas is deleted. The two randomly selected regions are combined with a constant region (C region) to form the functional gene. DNA between the randomly selected J area and the C area forms an intron. Its genetic code is deleted during the formation of a mature mRNA transcript.

The diagram below shows DNA from a lymphocyte before it is modified. A randomly-selected portion of the V region (orange) is combined with a randomly-selected portion of the J region (black). The DNA between these two regions is discarded.

 

The modified DNA is shown below. The remainder of the J region is an intron (green). It is removed from the pre-mRNA transcript. 

 

The region of V that is in front of the randomly selected segment (red) is not transcribed. The DNA between V and J was eliminated. The region between C and the randomly-selected part of J is removed from the pre-mRNA transcript as an intron. The mRNA transcript is shown below.

Because the DNA of the lymphocyte is changed, all of the antibodies produced by the cell will be identical. Moreover, when the cell reproduces by mitosis, all of its descendents will be genetically identical and produce the same kind of antibodies.

The variable region of the light and the heavy chains of antibodies and of B-cell and T-cell receptors are created by a similar process to that described above.

B Cells

B lymphocytes (B cells) mature in the bone marrow.
B cells have antigen receptors attached to their surface. They function to detect antigens by binding to the antigen.
All of the antigen receptors on the surface of one B cell are identical. A single B cell can therefore detect only one kind of antigen. Other B cells can detect other antigens. Our bodies have millions of different antigen receptors on B cells and can therefore detect millions of different antigens.
B cells must be activated before they can synthesize antibodies. Activation requires that the B cell attach to the antigen. The B cell must also be stimulated by a helper T cell that has also been exposed to the same antigen.
Once activated, the B cells will divide many times producing plasma cells, which in turn produce antibodies. The antibodies are identical to the receptors on the surface of the B cell that was initially stimulated by antigen. The antibodies therefore can adhere to the type of invader that initially activated the B cell.
Plasma cells do not have antigen receptors on their surface and they live for approximately 4 to 5 days.
Clonal selection refers to the idea that activated B cells and T cells produce a clone of cells, each capable of responding to the same antigen that was responsible for activating the parent cell.
Large numbers of B-cells are found in the lymph nodes and in the spleen.
Pathogens typically have many different antigens on their surface. A single infection will therefore result in the production of many different kinds of antibodies, each capable of attaching to an antigen on the surface of the pathogen.

Activation of B Cells

B cells must be activated before they divide to produce plasma cells and memory cells.
First, a specific antigen must attach to the antigen receptor on the surface of the B cell.
The particles bound to the antigen receptors of a B cell are brought into the cell by receptor-mediated endocytosis. This process encloses the particles within a vesicle and brings them into the cell. The vesicle will then fuse with a lysosome and digestive enzymes from the lysosome will digest the contents. The foreign proteins are broken down to peptide fragments.
The peptide fragments are attached to class II MHC proteins and then moved to the surface of the B cell.
A helper T cell that has been activated by exposure to the same antigen from an antigen displaying cell will bind to the B cell containing the antigen-MHC complex. The helper T cell will release signaling molecules called cytokines that stimulate the B cell to begin dividing and producing plasma cells and memory B cells.
This process is summarized below:

a B cell phagocytizes antigen, attaches fragments to MHC type II proteins, moves the antigen-MHC complexes to the surface → an activated helper T cell with matching antigen receptors attaches and releases cytokines → the B cell divides by mitosis producing a clone of genetically identical cells → some of the clone become plasma cells which secrete antibody, others become memory B cells

Immunological Memory

Activated B cells also divide to produce more B cells with the same type of antigen receptors. They are called memory B cells because they may remain in the body for many years, ready to respond to the same antigen. Memory helper T cells are also long-lived, enabling a quick response to the same infection.

Primary and Secondary Immune Response

There is a time delay from the time of first exposure to an antigen to the time when significant amounts of antibodies are produced. This is because B cells and T cells must be stimulated as discussed above. After this, clonal selection produces plasma cells and plasma cells produce antibodies. This sequence of events is called the primary immune response. Peak antibody production occurs between 10 and 17 days after initial exposure to the antigen.
After a primary immune response has occurred, memory B cells and memory T cells remain in the body. Future exposure to the same antigen will result in antibody production sooner and at higher levels due to the presence of these memory cells. This response to a subsequent infection is a secondary immune response.

Active and Passive Immunity

Active immunity is produced in individuals by administering foreign antigens. These antigens may come from weakened or dead microorganisms. This process is called vaccination.
Genetically engineered bacteria are currently being used to produce some antigens. Examples: malaria, hepatitis B.
After exposure to antigens in a vaccine, the level of antibodies in the blood begins to increase after several days, levels off, then declines. After a secondary exposure (called a booster), the level increases rapidly.
Memory B cells and memory T cells allow an individual to be actively immune. If the individual is exposed to the disease, a rapid immune response will occur because they already have large numbers of the correct B and T cells.

Passive immunity occurs when an individual receives antibodies instead of making their own. Passive immunity is short-lived because the person's B and T cells have not been stimulated to produce antibodies. The immunity lasts only as long as the antibodies they received remain in their bloodstream.

Examples of Passive Immunity

Newborn babies have antibodies they received from their mother.
Breast-fed babies receive antibodies from their mother's milk.

Allergies

Allergies are due to an overactive immune system.
Allergens are antigens that stimulate B cells to release IgE antibodies. IgE antibodies attach to mast cells in the connective tissues and to basophils in the blood. IgE antibodies attached to mast cells and basophils are able to bind to antigens. Mast cells and basophils will release histamine if their IgE antibodies attach to antigens (allergens).
Histamine causes mucus secretion, airway constriction, and inflammation due to blood vessels leaking. Leaky blood vessels cause the tissues to swell.
Allergy shots stimulate the body to produce high levels of antibodies. The antibodies react with the allergens before they have a chance to interact with the mast cells.

Lymphatic System

Functions of the Lymphatic System

1.  take up excess tissue fluid and return it to the circulatory system
2.  absorb fats at the intestinal villi and transports it to the circulatory system
3.  defend against disease

Lymphatic Vessels

Lymphatic vessels are similar to veins, including the presence of valves. They depend on the movement of skeletal muscles to move the fluid inside.
The fluid they contain is called lymph.
They empty into the circulatory system via the thoracic duct and the right lymphatic duct. The thoracic duct is much larger than the right lymphatic duct.

Lymph Nodes

Lymph nodes are small (1-25 mm), spherical or ovoid structures that are connected to lymphatic vessels. They contain open spaces (sinuses), each with many leukocytes which function to remove infectious pathogens and foreign particles.
The structures listed below are groups of nodules that also function to purify lymph:

tonsils - back of mouth
adenoids - back of mouth above the soft palate
Peyer's patches - intestinal wall

Spleen

The spleen stores blood.
It helps purify blood that passes through it by removing bacteria and worn-out or damaged red blood cells.

Thymus Gland

T lymphocytes mature in the thymus.

Bone Marrow

Most leukocytes are produced in the bone marrow. T lymphocytes mature in the thymus gland, small intestine, and in the skin.

Autoimmune Diseases

Autoimmune diseases result when the body produces antibodies that are capable of binding to its own tissues. They often appear in individuals that have recovered from other infections. Somehow the body seems to have learned to recognize its own antigens.

Examples

Myasthenia gravis - neuromuscular junctions are weakened
Multiple sclerosis - the myelin sheath of nerve fibers is attacked
Lupus erythematosus - Lupus is a chronic inflammatory disease. The skin, joints, kidneys and blood are most often affected but other organs may be affected as well.
Rheumatoid arthritis - the membranes that surround the joints are attacked
Type I diabetes - the insulin-producing cells (beta cells) of the pancreas are attacked

Summary of Cells Involved in Immunity

Neutrophils - phagocytize pathogens and foreign particles
Macrophages - phagocytize pathogens and foreign particles; function as antigen-presenting cells that activate T cells
Dendritic cells - phagocytic cells located on body surfaces that are in contact with the external environment; function as antigen-presenting cells that activate T cells
Monocytes - move out of the blood into other tissues and become macrophages
Eosinophils - kill parasites that are too large to phagocytize
Mast cells - secrete histamine when IgE receptors bind to antigen
Basophils - secrete histamine when IgE receptors bind to antigen
Natural Killer cells - kill virus-infected cells and cancer cells

B-lymphocytes - when stimulated, divide by mitosis to produce the following cell types:

Plasma cells - produce antibodies

Memory B lymphocytes - long-lived cells that are available to become activated if the body is exposed to the same antigen in the future.

T-lymphocytes

Helper T cells - secrete cytokines which activates B cells and cytotoxic T cells
Cytotoxic T cells - attack cells that bear antigens attached to MHC type 1 proteins
Memory helper T lymphocytes and memory cytotoxic T lymphocytes - long-lived cells that are available to become activated if the body is exposed to the same antigen in the future.

Digestive System

Introduction

Digestion is the chemical breakdown of large food molecules into smaller molecules that can be used by cells. The breakdown occurs when certain specific enzymes are mixed with the food.

Enzymes involved in Digestion

polysaccharides → maltose → glucose
proteins → peptides → amino acids
fats → fatty acids and monoglycerides

Mouth

Chewing breaks food into smaller particles so that chemical digestion can occur faster.

Enzymes

Salivary amylase breaks starch (a polysaccharide) down to maltose (a disaccharide).
Bicarbonate ions in saliva act as buffers, maintaining a pH between 6.5 and 7.5.
Mucins (mucous) lubricate and help hold chewed food together in a clump called a bolus.
The tongue contains chemical receptors in structures called taste buds. Theses are discussed in the chapter on sensory systems.
The tongue is muscular and can move food. It pushes food to back where it is swallowed.

Pharynx

The respiratory and digestive passages meet in the pharynx. They separate posterior to the pharynx to form the esophagus (leads to the stomach) and trachea (leads to the lungs).
Swallowing is accomplished by reflexes that close the opening to the trachea.
When swallowing, the epiglottis covers the trachea to prevent food from entering.
In the mouth, food is mixed with saliva and formed into a bolus.
Peristalsis refers to rhythmic contractions that move food in the gut. Peristalsis in the esophagus moves food from the mouth to the stomach.

Stomach

The stomach stores up to 2 liters of food.
Gastric glands within the stomach produce secretions called gastric juice.
The muscular walls of the stomach contract vigorously to mix food with gastric juice, producing a mixture called chyme.

Gastric juice

Pepsinogen is converted to pepsin, which digests proteins. Pepsinogen production is stimulated by the presence of gastrin in the blood (discussed below).
HCl

Hydrochloric acid (HCl) converts pepsinogen to pepsin which breaks down proteins to peptides. HCl maintains a pH in the stomach of approximately 2.0.
It also dissolves food and kills microorganisms.

Mucous protects the stomach from HCl and pepsin.

Secretion of Gastric Juice

Seeing, smelling, tasting, or thinking about food can result in the secretion of gastric juice.
Gastrin is a hormone that stimulates the stomach to secrete gastric juice. (See the discussion of hormones below.)

Ulcer

An ulcer is an irritation due to gastric juice penetrating the mucous lining of the stomach or duodenum. It is believed that ulcers are caused by the bacterium Helicobacter pylori, which, can thrive in the acid environment of the stomach. The presence of the bacteria on portions of the stomach lining prevents it from secreting mucous, making it susceptible to the digestive action of pepsin.

Duodenum

The duodenum is the first part of the small intestine.
Chyme enters through a sphincter.
It enters in tiny spurts.
At this point, proteins and carbohydrates are only partially digested and lipid digestion has not begun.

Pancreas

The pancreas acts as an exocrine gland by producing pancreatic juice which empties into the small intestine via a duct.
The pancreas also acts as an endocrine gland to produce insulin. (See the discussion on the Islets of Langerhans or Pancreatic Islets in the chapter on the endocrine system.)

Pancreatic Juice

Pancreatic juice contains sodium bicarbonate which neutralizes the acidic material from the stomach.
Pancreatic amylase digests starch to maltose.
Trypsin and Chymotrypsin digest proteins to peptides. Like pepsin (produced in the stomach), they are specific for certain amino acids, not all of them. They therefore produce peptides.
Lipase digests fats to monoglycerides and fatty acids.

Liver

The liver produces bile which is stored in gallbladder and sent to the duodenum through a duct.
Bile emulsifies fats (separates it into small droplets) so they can mix with water and be acted upon by enzymes.

Other Functions of the Liver

The liver detoxifies blood from intestines that it receives via the hepatic portal vein.
The liver stores glucose as glycogen (animal starch) and breaks down glycogen to release glucose as needed. This storage-release process maintains a constant glucose concentration in the blood (0.1%). If glycogen and glucose run short, proteins can be converted to glucose.
It produces blood proteins.
It destroys old red blood cells and converts hemoglobin from these cells to bilirubin and biliverdin which are components of bile.
Ammonia produced by the digestion of proteins is converted to a less toxic compound (urea) by the liver.

Hormones Involved in Digestion

The hormones listed below, like all hormones, reach their target cells by the circulatory system.

Hormone	Secreted by:	Stimulus for secretion	Effect
Gastrin	Stomach	Presence of food in the stomach	Stimulates the stomach to secrete gastric juice
Secretin	Duodenum	Chyme from the stomach	Stimulates the pancreas to produce sodium bicarbonate and the liver to secrete bile
CCK	Duodenum	Presence of food in the duodenum	Stimulates the gallbladder to release bile and the pancrease to produce pancreatic enzymes
GIP	Duodenum	Presence of food in the duodenum	Inhibits the gastric glands of the stomach and inhibits stomach motility

Gastrin

The presence of food in the stomach stimulates stretch receptors which relay this information to the medulla oblongata. The medulla stimulates endocrine cells in the stomach to secrete the hormone gastrin into the circulatory system. Gastrin stimulates the stomach to secrete gastric juice. This pathway of information is summarized below.

stretch receptors → medulla oblongata → endocrine cells in the stomach → gastrin → circulatory system → stomach → secretes gastric juice

Secretin

Secretin is produced by cells of the duodenum.
It’s production is stimulated by acid chyme from stomach.
It stimulates the pancreas to produce sodium bicarbonate, which neutralizes the acidic chyme. It also stimulates the liver to secrete bile.

CCK (cholecystokinin)

CCK production is stimulated by the presence of food in the duodenum.
It stimulates the gallbladder to release bile and the pancreas to produce pancreatic enzymes.

GIP (Gastric Inhibitory Peptide)

Food in the duodenum stimulates certain endocrine cells to produce GIP.
It has the opposite effects of gastrin; it inhibits gastric glands in the stomach and it inhibits the mixing and churning movement of stomach muscles. This slows the rate of stomach emptying when the duodenum contains food.

Small Intestine

The small intestine is approximately 3 m long.
Like the stomach, it contains numerous ridges and furrows. In addition, there are numerous projections called villi that function to increase the surface area of the intestine. Individual villus cells havemicrovilli which greatly increase absorptive surface area.
The total absorptive surface area is equivalent to 500 or 600 square meters.
Each villus contains blood vessels and a lacteal (lymph vessel).
Peptidases and maltase are embedded within the plasma membrane of the microvilli.

Peptidases complete the digestion of peptides to amino acids.
Maltase completes the digestion of disaccharides.

Absorption

Absorption is an important function of the small intestine.
Active transport moves glucose and amino acids into the intestinal cells, then out where they are picked up by capillaries.
Monoglycerides and fatty acids produced by the digestion of fat enter the villi by diffusion and are reassembled into fat (triglycerides). They combine with proteins and are expelled by exocytosis. They move into the lacteals for transport via the lymphatic system.

Large Intestine

The large intestine is also called the colon.
It receives approximately 10 liters of water per day. 1.5 liters is from food and 8.5 liters is from secretions into the gut. 95% of this water is reabsorbed.
The large intestine also absorbs sodium and other ions but it excretes other metallic ions into the wastes.
If water is not absorbed, diarrhea can result, causing dehydration and ion loss.
It absorbs vitamin K produced by colon bacteria.
The last 20 cm of the large intestine is the rectum.
Feces is composed of approximately 75% water and 25% solids. One-third of the solids is intestinal bacteria, 2/3’s is undigested materials.
The cecum is a pouch at the junction of the small intestine and large intestine. In herbivorous mammals, it is large and houses bacteria capable of digesting cellulose. In human ancestors, the cecum was larger but has been reduced by evolutionary change to form the appendix.

Polyps

Polyps are small growths in the epithelial lining of the colon.
They can be benign or cancerous and can be removed individually.
A low-fat, high-fiber diet promotes regularity and is recommended as a protection against colon cancer.

Appendix

The appendix is attached to cecum.
Appendicitis is an infection. The appendix may swell and burst, leading to peritonitis (infection of the abdominal lining).

Summary of Digestive Enzymes

The digestive enzymes in the table below are summarized according to type of food that they digest.

FOOD TYPE	ENZYME	SOURCE	PRODUCTS
CARBOHYDRATES	Salivary amylasePancreatic amylase Maltase	Salivary glandsPancreas Small intestine	MaltoseMaltose Glucose
PROTEINS	PepsinTrypsin Peptidases	Stomach mucosaPancreas Intestinal mucosa	PeptidesPeptides Amino acids
FATS	Lipase	Pancreas	Fatty acids and monoglycerides

The table below shows digestive enzymes grouped by source of the enzyme.

SOURCE	ENZYME	FOOD	PRODUCT
MOUTH (salivary glands)	Salivary amylase	Polysaccharides	Maltose
STOMACH	Pepsin	Proteins	Peptides
PANCREAS	Pancreatic amylaseTrypsin Lipase	PolysaccharidesProteins Fats	MaltosePeptides Fatty acids and monoglycerides
SMALL INTESTINE	MaltasePeptidases	MaltosePeptides	GlucoseAmino acids

Practice

Fill in the source of each enzyme in the table below and state the product produced by the enzyme.

FOOD TYPEenzyme	SOURCE	PRODUCTS
CARBOHYDRATESsalivary amylase pancreatic amylase disaccharidases
PROTEINSpepsins trypsin, chymotrypsin carboxypeptidase aminopeptidase
FATSlipase

Respiratory System

Introduction

Oxygen is needed by aerobic organisms because it is the final electron acceptor during cellular respiration. The diagram below shows that Cellular respiration is a process in which electrons are removed from glucose in a series of steps. The electrons are carried by NADH and FADH2 to the electron transport system. The electron transport system uses the energy in the electrons to synthesize ATP. The remaining carbon atoms in the glucose molecule are released as CO₂, a waste product. The equation for the complete breakdown of glucose by aerobic eukaryotes  is:
 C₆H₁₂O₆  +  6O₂  -->   6CO₂  +  6H₂O  +  36 ATP

Atmosphere

78% N₂, 21% O₂, 1% argon, noble gases, CO₂

Some Properties of Gases

Diffusion refers to movement of molecules from an area of higher concentration to an area of lower concentration.
Partial pressure is the pressure exerted by one gas in a mixture.

Total atmospheric pressure at sea level = 760 mm Hg.
Partial pressure O₂ = 760 X .21 = 160 mm Hg.

Gasses move by diffusion from areas of higher partial pressure to areas of lower partial pressure.

Respiratory Surfaces

All animals need to take in O₂ and eliminate CO₂. Lungs are membranous structures designed for gas exchange in a terrestrial environment. Gills are designed for gas exchange in an aquatic environment.
Oxygen must be dissolved in water before animals can take it up. Therefore, the respiratory surfaces of animals (gills, lungs, etc.) must always be moist. This is true of all animals.
Very small organisms don't need respiratory surfaces because they have a high surface:volume ratio.

Skin

The skin can be used as a respiratory surface but it does not have much surface area compared to lungs or gills. Animals that rely on their skin as a respiratory organ are small and either have low metabolic rates or they also have lungs or gills.
Like all respiratory surfaces, the skin must remain moist to function in gas exchange.
Amphibians, most annelids, some mollusks, and some arthropods use their skin as a respiratory organ.

Gills

Gills provide a large surface area for gas exchange in aquatic organisms.
It is difficult to circulate water past gills because water is dense and the O₂ concentration in water is low. There is 5% as much oxygen in water as there is in air. To circulate water past the gills, amphibian larvae physically move their gills, mollusks pump water into mantle cavity which contains the gills, and some crustacean gills are attached to branches of the walking legs.
The flow of blood in the gills of fish is in the opposite direction that water passes over the gills. This arrangement (called countercurrent flow) enables fish to extract more oxygen from the water than if blood moved in the same direction as the passing water.

Gills cannot be used in air because they lack structural support; they would collapse. Their use in air would also result in too much water loss by evaporation.

Tracheal System

Insects, centipedes, and some mites and spiders have a tracheal respiratory system.
Tracheae are a network of tubules that bring oxygen directly to the tissues and allow carbon dioxide to escape. The openings to the outside, called spiracles, are located on the side of the abdomen.
Trachea and lungs are internal to reduce water loss.

Vertebrate Lungs

Simple lungs evolved 450 million years ago in fish.

Some evolved into swim bladders.
Others evolved into more complex lungs.

Paired lungs are the respiratory surfaces in all reptiles, birds, and mammals.

Amphibians

lung is a simple convoluted sac
have small lungs but obtain much O₂ by diffusion across moist skin
ventilate lungs by positive pressure; (reptiles, birds and mammals use negative pressure)

Reptiles

The skin is watertight; it is not used as a respiratory surface.
The lungs possess alveoli.
All diffusion occurs across the alveolar surface.

Birds and Mammals

The lungs of birds and mammals are more branched with smaller, more numerous alveoli.

Birds

Birds have one-way flow of air in their lungs. As a result, the lungs receive fresh air during inhalation and again during exhalation.
advantages of one-way flow:

no residual volume; all old (stale) air leaves with each breath
crosscurrent flow (crosscurrent = 90 degrees ; countercurrent = 180 degrees; crosscurrent is not as efficient but is still more efficient than mammalian lung)

One-way flow is accomplished by the use of air sacs as illustrated below. During inspiration, the air sacs fill. During expiration, they empty.

  

Human Respiratory System

Surface area of human lung is 60 to 80 sq. meters

Structures

pharynx -->  epiglottis (open space is the glottis) -->  larynx with vocal cords -->  trachea -->  bronchi -->  bronchioles -->  alveoli

Nasal Cavities

hair and cilia filter dust and particles.
Blood vessels warm air and mucus moistens air.

Ventilation

To inhale, the diaphragm contracts and flattens.
Muscles move the rib cage which also contributes to expanding the chest cavity.
To exhale, the muscles relax and elastic lung tissue recoils.

The Heimlich Maneuver

Choking results when food enters the trachea instead of the esophagus.
The Heimlich maneuver can force air out of the lungs to dislodge the obstruction.

Respiratory pigments

Hemoglobin

Hemoglobin is a protein that carries oxygen and is found in the blood of most animals.
It is synthesized by and is contained within erythrocytes (red blood cells).
Oxygen is bound reversibly to the iron portion.
Hemoglobin increases the oxygen-carry capacity of the blood by 70 times. 95% of the oxygen is transported by hemoglobin, 5% in blood plasma.
The bright red color occurs when it is bound with oxygen.

Hemocyanin

Hemocyanin is a carrier protein found in many invertebrates
It uses copper instead of iron.
It does not occur within blood cells; it exists free in the blood. (Their blood is called hemolymph.)
It is bright blue when bound with oxygen.

Gas Exchange and Transport

Gas Exchange in humans occurs in alveoli. Gasses must diffuse across the alveolar wall, a thin film of interstitial fluid, and the capillary wall.

Partial pressures

	LUNGS	TISSUES
OXYGEN	high	low
CO2	low	high

The partial pressure of CO₂ is higher in the tissues because respiring tissues produce CO₂ as a result of the breakdown of glucose (C₆H₁₂O₆) during cellular respiration.

Oxygen Transport

1 hemoglobin molecule + 4 oxygen molecules -->  oxyhemoglobin.
The amount of oxygen that combines depends upon the partial pressure. More oxygen is loaded at higher partial pressures of oxygen.
Hemoglobin does not necessarily release (unload) all of its oxygen as it passes through the body tissues. Oxyhemoglobin releases its oxygen when:

-the partial pressure of O₂ is low.
-the partial pressure of CO₂ is high. High CO₂ causes the shape of the hemoglobin molecule to change and this augments the unloading of oxygen.
-the temperature is high.
-the pH is low (high acidity).

Active tissues need more oxygen and all of the conditions listed above are characteristic of actively metabolizing tissues. Therefore, these tissues receive more oxygen from hemoglobin than less active tissues.
CO (carbon monoxide) binds to hemoglobin 200 times faster than O₂ and does not readily dissociate from the hemoglobin. Small amounts of CO can cause respiratory failure.

Carbon Dioxide Transport

Carbon dioxide is transported to the lungs by one of the following ways:

dissolved CO₂
bound to hemoglobin (HbCO₂)
HCO₃^- (bicarbonate ions).

Most CO₂ enters red blood cells where bicarbonate ions are produced.

CO₂   +   H₂O    <-->     H₂CO₃    <-->     HCO₃^-   +   H⁺                                       carbonic           bicarbonate
                                          acid                     ion

The hemoglobin picks up the H⁺, preventing the blood from becoming acidic. The bicarbonate ion diffuses into the plasma where it is transported.
In the lungs, the partial pressure of CO₂ is low, so the equation above moves toward the left. Bicarbonate ions enter red blood cells, hemoglobin releases its hydrogen ions, and CO₂ is released.
The equation above moves toward the right when the partial pressure of CO₂ is high. When the partial pressure of CO₂ is low, it moves to the left and CO₂ comes out of solution.
In the active tissues, the CO₂ partial pressure is high, so CO₂ becomes dissolved in water, forming H₂CO₃, which then forms HCO₃^- and H⁺. In the lungs, the partial pressure of CO₂ is low because the concentration of CO₂ in the atmosphere is low. As blood passes through the lungs, HCO₃^- + H⁺ form H₂CO₃ which then forms CO₂ + H₂O.
Carbonic anhydrase (in red blood cells) speeds up this reaction 150 times.

Control of breathing rate

Eliminating CO₂ is usually a bigger problem for terrestrial vertebrates than obtaining O₂. The body is therefore more sensitive to high CO₂ concentration than low O₂ concentration.
Aquatic vertebrates are more sensitive to low O₂ because O₂ is more limited in aquatic environments.

Neural Control Mechanisms in terrestrial vertebrates

During inhalation, the diaphragm and intercostal muscles are stimulated. Other neurons inhibit these when exhaling.
Respiration is not under voluntary control.

Monitoring H⁺ and CO₂

Chemoreceptors in the respiratory control center of the brain (medulla oblongata) detect changes in CO₂ by monitoring pH of cerebrospinal fluid. High CO₂ lowers the pH (an acid is a solution with a high H⁺concentration).

CO₂ + H₂O -->  H₂CO₃ -->  HCO₃^- + H⁺

Chemoreceptors in the aorta and carotid artery are also sensitive to pH and to greatly reduced amounts of O₂.

Bronchiole diameter

The primary bronchus branches extensively into bronchioles. Terminal bronchioles are surrounded by smooth muscle.
The diameter of the bronchioles (and blood vessels) increases or decreases in response to needs. It is adjusted by smooth muscle under the control of the nervous system. The parasympathetic nervous system(discussed in the chapter on nervous systems) stimulates these muscles to contract, reducing the diameter of the airways. This is advantageous when the body is relaxing and breathing is shallow. Narrow bronchioles result in less air remaining within the lungs after each exhalation.
The sympathetic nervous system relaxes these muscles as a response to stressful situations. This allows a more rapid rate of intake and expulsion of air.
Allergens trigger histamine release which constricts muscles.

Narrower bronchioles result in decreased ventilation of the lungs.
Severe attacks may be life-threatening.

Defense Mechanisms in the Respiratory Tract

Large particles are filtered out by the nose.
Small particles become trapped in mucous and are moved upward, out of the respiratory tract by cilia lining the bronchi and bronchioles.

Bronchitis

Bronchitis is an inflammation of the airways that causes mucous to accumulate. The normal cleansing activity of cilia is reduced and not sufficient to remove the mucous. Coughing attempts to clear the mucus.
Smoking and other irritants increase mucus secretion and diminish cilia function.

Emphysema

Emphysema occurs when the alveolar walls lose their elasticity. Damage to the walls also reduces the amount of surface available for gas exchange.
Emphysema is associated with environmental conditions, diet, infections, and genetics. It can result from chronic bronchitis when the airways become clogged with mucous and air becomes trapped within the alveoli.

Effects of Cigarette Smoke

Cigarette smoke prevents the cilia from beating and stimulates mucus secretion.
Coughing is necessary to expel excess mucous but it contributes to bronchitis and emphysema.
Cigarette smoke also kills phagocytic cells in respiratory epithelium. These cells normally help rid the lungs of foreign particles and bacteria.
Cigarette smoke contains compounds that are modified in the body to form carcinogens.
Smoking causes 80% of lung cancer deaths.

Excretory Systems

Excretory System

Function of the Excretory System

The excretory system functions in ridding the body of nitrogenous (nitrogen-containing, discussed below) and other wastes.
It also regulates the amount of water and ions present in the body fluids.

Review of Excretory Systems in Animals

Water Balance

Isotonic Animals

The concentration of solutes in isotonic animals is approximately equal to that of their environment. As a result, they do not gain or lose water.
Only marine invertebrates and cartilaginous fish (chondrichthyes) are isotonic.
The concentration of solutes in the tissues of isotonic animals is approximately equal to that of the ocean. This is 100 times higher than that found in the mammalian bodies. The high concentration of solutes in chondrichthyes is due mostly to the presence of urea.

Marine Bony Fish

The rate of water loss is high in marine bony fish. They drink water seawater at a rate of approx. 1% of their body weight/hour.
Specialized cells in the gills excrete excess salt.

Freshwater Bony Fish

Freshwater bony fish tend to gain water from their environment due to osmosis.
They produce large quantities of dilute urine (approx. 1/3 of their body weight/day) and do not drink water.
Salt-absorbing cells in he gills use active transport (energy is required) to pump salts into their body.

Birds and reptiles near the sea

Birds and reptiles living near the sea consume a large amount of salt in their diet. Nasal salt glands remove this excess salt from their body by secreting a concentrated salt solution.

Sea Mammals

The kidneys of sea mammals (ex: seals, whales, porpoises) are able to maintain a constant salt concentration in their bodies by producing urine that has a high concentration of salt.
They are able to drink seawater because the salt concentration of their urine is higher than that of sea water.

Terrestrial Animals

Most terrestrial animals drink water, some do not.
Metabolic water produced from cellular respiration may be sufficient to meet the needs of some animals. The equation below shows that six molecules of water are produced for every molecule of glucose oxidized.

C₆H₁₂O₆ + 6O₂  --> 6CO₂ + 6H₂O + 36 ATP

Example: Kangaroo Rat
Kangaroo rats of southwestern US deserts never have to drink. Their water comes from metabolic water released during cellular respiration and water present in their food.
They emerge from their burrows only at night, when the air is cooler and more humid than during the day. This helps prevent water loss from their bodies and reduces the amount needed to keep cool (sweating).
They avoid movement while in their burrow. This minimizes heat production and thus, the need for sweating.
Dry food stored in their burrows absorbs moisture lost in breathing. This moisture is taken back in when the food is eaten.
Their noses become cooled during inhalation as a result of evaporating water but the cooled membranes cause the moisture to condense during exhalation.
Their large intestine absorbs almost all water present in the digestive tract. Their feces are dry, hard pellets.
Their kidneys conserve water by excreting concentrated urine.

Organs of Excretion

Contractile Vacuoles

paramecium

Flame Cells, Protonephridia

Planarians have two protonephridia composed of branched tubules that empty wastes through excretory pores on their surface. The protonephridia contain numerous bulblike flame cells with clustered, beating cilia that propel fluid into the tubules.
These structures function in waste excretion and osmotic regulation.

Metanephridia

Earthworms have two metanephridia in almost all of the body segments.
Each metanephridium consists of a tubule with ciliated opening (nephrostome) on one end and an excretory pore (nephridiopore) that opens to the outside of the body at the other end. Fluid is moved in by cilia. Some substances and water are reabsorbed in a network of capillaries that surround the tubule.
This system produces large amount of urine (60% of body wt./day).

Malpighian Tubules

The excretory organs of insects are malpighian tubules. They collect water and uric acid from surrounding hemolymph (blood) and empty it into the gut. Water and useful materials are reabsorbed by the intestine but wastes remain in the intestine.

Kidneys

The kidneys of vertebrates (discussed below) function in the removal of nitrogenous and other wastes and in osmotic regulation of the body fluids.

Nitrogenous wastes

Cells use amino acids to construct proteins and other nitrogen-containing molecules. Amino acids can also be oxidized for energy or converted to fats or carbohydrates.
When amino acids are oxidized or converted to other kinds of molecules, the amino (NH₂) group must be removed. The nitrogen-containing compounds produced as a result of protein breakdown are toxic and must be removed by the excretory system.
Nitrogenous wastes of animals are excreted in form of ammonia, urea, or uric acid.

Ammonia

Ammonia is formed immediately after the amino group is removed from an amino acid. This process requires very little energy.
Ammonia is highly soluble in water but very toxic. Aquatic animals such as bony fishes, aquatic invertebrates, and amphibians excrete ammonia because it is easily eliminated in the water.

Urea

Terrestrial amphibians and mammals excrete nitrogenous wastes in the form of urea because it is less toxic than ammonia and can be moderately concentrated to conserve water.
Urea is produced in the liver by a process that requires more energy to produce than ammonia does.

Uric Acid

Insects, reptiles, birds, and some dogs (Dalmatians) excrete uric acid. Reptiles and birds eliminate uric acid with their feces. The white material seen in bird droppings is uric acid.
It is not very toxic and is not very soluble in water. Excretion of wastes in the form of uric acid conserves water because it can be produced in a concentrated form due to its low toxicity.
Because it is relatively insoluble and nontoxic, it can accumulate in eggs without damaging the embryos.
The synthesis of uric acid requires more energy than urea synthesis.

Mammals

Structures of the excretory system

kidneys
ureters
urinary bladder
urethra

Regions of the Kidney

cortex (outer)
medulla (inner)
renal pelvis (innermost chamber)- collects the urine

Nephrons

microscopic; about 1 million/kidney
some are primarily in the cortex, others dip down into the medulla

Parts

glomerulus- a capillary tuft from which fluid leaves the circulatory system (filtration)
Bowman's capsule- a funnel-like structure that collects filtrate from the glomerulus
proximal convoluted tubule
loop of the nephron
distal convoluted tubule
collecting duct- delivers urine to renal pelvis

Blood Supply

The path of blood flow through a kidney is listed below.
Blood enters the kidney through a branch of the aorta called the renal artery.
Branches of the renal artery within the kidney produce afferent arterioles.
Each afferent arteriole leads to a network of capillaries called a glomerulus. Fluid leaks out of the capillaries of the glomerulus but large molecules and cells do not fit through the pores. This process is called filtration.
Blood leaves the capillaries of the glomerulus via an efferent arteriole and enters capillaries in the medulla called peritubular capillaries, which collect much of the water that was lost through the glomerulus.
Venules from the peritubular capillaries lead to the renal vein, which exits the kidney and returns blood to the inferior vena cava.

Urine Formation

Glomerulus

Pressure filtration occurs in the glomerulus.
Blood enters the glomerulus via an afferent arteriole where blood pressure forces water and small molecules out through pores in the glomerular capillaries.
The filtrate has approximately the same composition as tissue fluid.
Blood leaves the glomerulus via the efferent arteriole.
Approximately 45 gallons of liquid per day are filtered from the blood in the glomerulus.

Proximal Convoluted Tubule

A large amount of nutrients and water is filtered from the blood in the glomerulus. It is necessary to reabsorb most of the nutrients and water but leave wastes in the tubule.
Selective reabsorption occurs in the proximal convoluted tubule. Glucose, vitamins, important ions and most amino acids are reabsorbed from the tubule back into the capillaries near the proximal convoluted tubule.
These molecules are moved into the peritubular capillaries by active transport, a process that requires energy.
Cells of the proximal convoluted tubule have numerous microvilli and mitochondria which provide surface area and energy.
When the concentration of certain substances in the blood reaches a certain level, the substance is not reabsorbed; it remains in the urine. This prevents the composition of the blood from fluctuating. This process regulates the levels of glucose and inorganic ions such as sodium, potassium, bicarbonate phosphate, and chloride.
Urea remains in the tubules.
Without reabsorption, death would result from dehydration and starvation.

Loop of Henle

In mammals, the loop of Henle conserves water resulting in concentrated urine.
This is done by the gut in birds and reptiles.

Descending Loop

Water moves out of the descending loop as it passes through the area of high salt concentration produced by the ascending loop.
The descending loop is not permeable to ions.

Ascending Loop

Fluid that moves into the lower part of the ascending loop is concentrated. This part of the loop is permeable to Na+ and Cl-. These ions move out, contributing the high osmotic concentration.
As fluid moves further up the ascending loop, salt is actively pumped out.
This ascending loop is impermeable to water reentry.
The ascending loop thus creates a concentration gradient with a higher concentration in the medulla (interior region).

Countercurrent Mechanism, Collecting Duct

The movement of sodium out of the ascending loop and into the medulla results in water loss and concentrated urine in the descending loop. The water loss and increased salt concentration that occurs in the descending loop further enhances the ability of the ascending loop to pump more salt out into the medulla. High salt in the medulla acts to help remove water in the descending loop. This phenomena is called the countercurrent multiplier because the effect of the ascending loop enhances the effect of the descending loop and the effect of the descending loop enhances the effect of the ascending loop.
Urea is concentrated in the fluid; some is able to move out of the lower portion of the collecting duct. It does not enter the blood stream, however, so little urea is lost once a concentration gradient is established.
The combination of urea and salt produces a high osmotic concentration in the medulla.

Length of the Loop of Henle

A longer loop of Henle will function to produce a greater concentration of urea and salt in the medulla. The higher concentration gradient enables the removal of more water as fluid moves through the collecting duct.
The length of the loop of Henle varies among mammals. The beaver, which does not need to conserve water, has a relatively short loop.
Desert-dwelling mammals have very long loops and are capable of producing extremely concentrated urine resulting in very little water loss.

Distal Convoluted Tubule

Some wastes are actively secreted into the fluid in the distal convoluted tubule by a process called tubular secretion. Some of these are H⁺, K⁺, NH₄⁺ toxic substances and foreign substances (drugs, penicillin, uric acid, creatine).
Secretion of H⁺ adjusts the pH of the blood.

Collecting Duct

Several renal tubules drain into a common collecting duct.
The collecting ducts pass through the concentration gradient that was established by the loops of Henle. As fluid passes through the collecting ducts, much of the water moves out due to osmosis. The permeability of the collecting duct to water is regulated by hormones (discussed below).

Hormones that Regulate Water Loss

Antidiuretic Hormone (ADH)

ADH increases the permeability of the distal convoluted tubule and collecting duct.
If the osmotic pressure of blood increases (becomes more salty, not enough water); the posterior pituitary will release ADH and the permeability of the collecting ducts will increase, allowing water to leave by osmosis. The water returns to the blood.
If osmotic pressure of blood decreases, pituitary does not release ADH and more water is lost in urine due to decreased permeability of the collecting duct.
Alcohol inhibits the secretion of ADH, thus increases water loss.
Diuretic drugs cause increased water loss in urine, lowering blood pressure.

Aldosterone

Aldosterone secretion is not under the control of the anterior pituitary.
When pressure is low, the afferent arteriole cells secrete renin.
Renin initiates a series of chemical reactions that ultimately result in the adrenal cortex releasing aldosterone, which acts primarily on the distal convoluted tubule to promote absorption of sodium and excretion of potassium. (renin => adrenal cortex => aldosterone => distal convoluted tubule => reabsorption of sodium from the tubule and excretion of potassium)
The increased osmotic pressure associated with increased sodium levels contributes to the retention of water and thus increased blood volume. In the absence of aldosterone, more sodium is excreted and the lower sodium levels result in decreased blood volume and lower blood pressure.

Atrial Natriuretic Hormone

The presence of too much blood in the circulatory system stimulates the heart to produce atrial natriuretic hormone. This hormone inhibits the release of aldosterone by the adrenal cortex and ADH by the posterior pituitary causing the kidneys to excrete excess water. The loss of water and sodium contribute to lowering the blood volume.

pH of the Blood

Breathing

Adjustment of the breathing rate can make slight alterations in the pH of the blood by reducing the amount of carbonic acid. Rapid breathing moves the equation below to the left, thus increasing the pH (less acidic). Slow breathing results in less CO₂ being given off and the equation moves to the right.

CO₂ + H₂O -->  H₂CO₃ -->  HCO₃^- + H⁺

Kidneys

The kidneys provide a slower but more powerful means to regulate pH. They excrete or absorb hydrogen ions (H⁺) and bicarbonate ions (HCO₃^-) as necessary for adjusting pH.
When the pH is low (acidic), hydrogen ions are excreted and bicarbonate ions are reabsorbed. The loss of hydrogen ions from the blood make it less acidic. Bicarbonate ions in the blood also reduce pH by taking up hydrogen ions (see the equation above).
When the pH is too high (too basic), fewer hydrogen ions are excreted and fewer sodium and bicarbonate ions are reabsorbed.