Organs of protection and detoxification
Toxins can enter the body in three
ways: by absorption through the skin;
by inhalation through the respiratory tract
into the lungs; or by ingestion through the
mouth into the gastrointestinal tract. The
skin, lungs, intestines, and kidneys have all
developed some protective mechanisms and
methods of detoxification, although the liver
is the body's major organ of detoxification.
The skin
The skin consists of two major layers. The
outer layer, the epidermis, is made of four
thin layers of epithelial cells. The inner
layer, the dermis, is composed of connective tissue.
- THE EPIDERMIS
- This outer layer of protective skin is approximately 1 millimeter thick and is composed of
tightly packed cells. The top layer of the epidermis is pigmented and varies in thickness
in different areas of the body, determining
how easily chemicals can penetrate the skin
and how rapidly they are absorbed. An exception is the palm of the hand, where this layer is thicker than in other areas of the
body, yet absorbs chemicals more readily.
New skin cells form in the basal cell
layer, replacing the entire epidermis approximately once a month. Melanocyte cells,
which form part of the epidermis, produce
melanin pigment. Melanin determines skin
color, and also protects against ultraviolet
injury, sunburn, and skin cancer. Melanin
absorbs ultraviolet and visible light, and quenches free radicals.
Epidermal cells produce lipids and a protein called keratin. Lipids, which include
cholesterol and free fatty acids, help protect
the skin against water loss and cracking.
With the aid of sunlight, the epidermis also
produces vitamin D, an essential nutrient
for maintaining calcium and phosphate levels in the body (needed for the growth and repair of bones).
- THE DERMIS
- The thicker dermis lies under the epidermis
and is composed of the proteins collagen
and elastin. These proteins make the skin
elastic and give it strength. Unlike the epidermis, it is well supplied with blood, lymph
vessels, and nerves.
The dermis also contains the eccrine and
apocrine sweat glands, sebaceous glands,
and hair follicles. Eccrine sweat glands are
distributed over the body's surface, helping
to regulate its temperature. Apocrine sweat
glands open into hair follicles and lose cells
as they release secretions. Sebaceous glands
are located near hair follicles. They secrete
sebum, a lipid mixture that has some antibacterial and antifungal properties. Sebum
also helps the body excrete lipid-soluble toxins, but only in small amounts.
- HOW TOXINS ENTER THE SKIN
- Toxins vary in their ability to enter the skin,
and several factors affect their absorption. To
be absorbed, a toxin must also be somewhat
water-soluble. Toxins that are only lipid-soluble or only water-soluble are poorly absorbed. Oily solutions usually penetrate the
skin easily, as it readily absorbs lipids. When
the skin is wet, water-soluble chemicals penetrate more easily. At higher environmental
temperatures, the skin is more absorbent. In
addition, chemicals penetrate cracked or injured skin more easily than intact skin.
Some toxins are absorbed directly through
hair follicles in the skin.
Solvents can easily penetrate the skin because of their lipid (fat) solubility. Caustic
chemicals, such as acids and alkaline solutions, can also penetrate the skin. Once a
chemical has penetrated the epidermis, it
moves into the dermis. The rich blood supply of the dermis readily transports the
chemical into the bloodstream.
- PROTECTIVE DEVICES
- The normal microbial flora of the skin is a
major barrier to infection, as is the sebum.
Although sebum helps to prevent the invasion of substances from the external environment, such as bacteria, it cannot block
the absorption of toxins through the skin.
The epidermal cells are also capable of producing a variety of lipids that afford protection similar to that of sebum, but cannot
stop toxins. Hair on the skin can be protective if it prevents a toxic substance from reaching the skin.
Some people use physical barriers in an
attempt to protect against toxic skin exposures. Barrier creams are one method, although they cannot usually block toxin absorption. Rubber gloves may be useful, but
some chemicals and microorganisms can
penetrate the gloves. Thin plastic gloves prevent toxins from contacting the skin. However, if a chemical gets inside the glove, it
will actually be absorbed more readily.
- DETOXIFICATION
- Because it contains the enzyme cytochrome P-450 the skin can metabolize drugs,
steroid hormones, and some xenobiotics. It
converts these chemicals into more water-soluble forms, which can then be excreted
from the body. Small amounts of toxins are
eliminated in the sweat excreted from the
pores and through the sebaceous glands of the skin.
The lungs
The lungs are part of the respiratory tract.
The upper air passage of the respiratory tract consists of the nose, the pharynx, the hypo-pharynx, and the larynx, which houses the
vocal cords. The lower air passage stretches
from the vocal cords through the trachea and into the lungs.
As we breathe, air enters the upper passage, then traverses the trachea. This area is
the narrowest cross-section of the entire airway. The trachea branches into the right and
left main stem bronchi, or bronchial tubes,
behind the ribcage. One bronchi enters each
lung. The bronchi then divide into two to
three more branches, called bronchioles.
The bronchioles lead to air sacs called alveolar sacs or alveoli. Their total surface area is
estimated to be 70 square meters.
Oxygen is extracted from the air we
breathe into the lungs and supplied to millions of alveoli, which pass oxygen molecules into the capillaries. Oxygen then combines with hemoglobin in the red blood cells
and is carried to the rest of the body.
Exhaling diffuses carbon dioxide molecules from the capillaries into the alveoli and
expels them from the body through the
bronchi, trachea, and upper air passage.
Three diseases affect the bronchial tube
system: asthma, bronchitis, and emphysema. Asthma is characterized by attacks of
breathing difficulty. Bronchitis is an inflammation of the bronchial tubes. Toxins can
trigger both asthma and bronchitis, which
are reversible in their early stages. The toxins in cigarette smoke can cause both
chronic bronchitis and emphysema. Emphysema destroys lung elasticity by damaging the walls separating the alveoli from one
another, creating tiny craters. Other alveoli become permanently enlarged. Emphysema
is irreversible.
- HOW TOXINS ENTER THE LUNGS
- The lungs have the greatest exposure of any
organ to the environment. The air we
breathe contains microorganisms, chemicals, dust, and pollution. Small solid particles and liquid aerosols can easily enter
the lungs and be deposited in three ways:
impaction, sedimentation, and diffusion.
Gases are absorbed directly through the cells
lining the respiratory tract.
- IMPACTION
- In impaction, large particles continue in
straight paths through the airway passages.
Most larger particles land on the surface of
the nose and throat area (nasopharynx) or at
the branching of the bronchi. These particles become embedded in mucus or trapped
by nasal hairs and are eliminated by sneezing, swallowing, or blowing the nose. The nasopharynx removes 95 percent of particles 5 microns or larger.
- SEDIMENTATION
- Medium-sized particles, 1 micron (the size
of a cell) to 5 microns in diameter, are deposited in the lungs by sedimentation. Most
of these land in the mucus layer of the bronchioles, and are eventually either moved up
in the mucus and exhaled, or swallowed. If
the particles do reach the alveoli, they can become trapped permanently and may damage the lungs.
- DIFFUSION
- The smallest aerosol particles, less than 0.1
micron in diameter, are deposited in the
lungs by diffusion. Many of these particles are exhaled immediately, but those that become trapped can eventually cause lung disease, known as pneumoconiosis. Two types
of pneumoconiosis are asbestosis, caused by
asbestos fibers, and silicosis, caused by silica dust.
- ABSORPTION
- Gases are absorbed differently in the respiratory tract, depending on their solubility and
flow rate, and the duration of exposure. Most
absorption of gases takes place in the upper
air passages. Some gases dissolve in the
fluid that lines the epithelium (the cell layer
lining the respiratory tract).
The nose absorbs gases more readily
when air flow is increased, which may account for increased absorption by physically
active people. The gas may also alter the lining fluid, so that the rate of absorption is increased.
- PROTECTIVE DEVICES
- The lungs protect themselves against environmental pollutants with filters, epithelial
barriers, enzyme systems, and immune responses. Filters include mucus and cilia.
Mucus is produced by glands located beneath the epithelium. Certain cells contain
cilia, which are hair like projections that beat
in a synchronized fashion at about a thousand times per minute. Together, mucus
traps particles and cilia help to move them
out of the lungs. A person can then sneeze
and cough out the irritants. However, cilia
cannot transport particles if there is insufficient mucus. Influenza virus can paralyze
the cilia, leading to secondary bacterial infections. Some people have a condition known
as immotile cilia syndrome, which means their cilia do not move, and they are prone to
sinus and respiratory tract infections.
Epithelial barriers consist of special cells
in the epithelium. Alveolar macrophages, a
type of white cell, ingest particles, and kill
bacteria and viruses, which they then present to lymphocytes. The lymphocytes,
another type of white cell, destroy them.
Alveolar macrophages also contain aryl hydrocarbon hydroxylase, a type of enzyme that detoxifies chemicals.
In addition, an enzyme system helps to
protect the lungs. When particles are inhaled, inflammatory enzymes, known as
proteases, are released. These proteases can
damage the lung cells or the connective tissue in the lungs. Specific proteins known as
antiproteases protect the alveoli by combining with proteases to inactivate them. Cigarette smoke destroys the balance between
proteases and antiproteases, increasing the
activity of the proteases. The most common
antiprotease is alpha-I-anti-trypsin. People
with a deficiency of this antiprotease are more prone to emphysema.
- DETOXIFICATION
- The lungs contain enzymes from the mixed function oxidase family, enabling them to
metabolize drugs and xenobiotics to more
water-soluble chemicals, which can then be
excreted by the kidneys.
The lungs also have antioxidant enzymes to counteract free radicals, including
superoxide dismutase, glutathione enzymes, and catalase. In addition, alveolar
lining fluid, containing transferrin, ceruloplasmin, and glutathione, protects the lungs
from oxidant stress. Vitamin E, an antioxidant found in cell membranes, protects the
lungs against toxic lipid peroxides produced
by the cell membranes of the lungs when attacked by organisms. In patients who smoke
cigarettes, the fluid lining the alveloi can be
deficient in vitamin E.
Finally, the lungs have immune responses to protect them against inhaled organisms. Lymphocytes in the lungs produce
immunoglobulins (antibodies), while other
immunoglobulins cross from the blood into
the lungs. Immunoglobulins IgA, IgG, and
IgE have all been found in the respiratory
tract. IgA neutralizes many viruses, and it
seems to prevent antigen absorption across
the lung cells. T-lymphocytes (white blood
cells that help fight infection) help protect
the lungs against microbes and tumor cells.
T-lymphocytes also release lymphokines,
which are molecules that activate and stimulate macrophages (white blood cells that ingest foreign material).
The gastrointestinal tract
The gastrointestinal (GI) tract includes the
mouth, pharynx, esophagus, stomach, small
intestine, large intestine, and rectum. The
other portion of the gastrointestinal system
is made up of glandular organs that secrete
substances into the gastrointestinal tract.
These glands include the salivary glands,
liver, gallbladder, and pancreas. The function of the gastrointestinal system is to
process the food we eat into a form that the
circulatory system can distribute to the cells of the body.
The GI tract is a tube that runs through
the body from the mouth to the anus. In
adults, this tube is approximately 15 feet long. The contents of the lumen, which is
the interior of this tube, are technically outside the body. For example, millions of bacteria populate the large intestine. Most of
them are beneficial, but if these bacteria
should leave the intestine and enter the
body, they are harmful and can even be lethal.
Food is taken into the mouth where it is
mixed with saliva, which moistens and lubricates the food particles so they may be swallowed easily. The saliva contains an enzyme
called amylase that aids in digesting carbohydrates.
The pharynx and esophagus serve as a
pathway to deliver the food from the mouth
to the stomach. The movement of these two
parts of the gastrointestinal tract controls
the process of swallowing.
The stomach mixes the food with hydrochloric acid, pepsin, gastrin, and mucus.
The pepsin processes protein, and gastrin
stimulates the release of hydrochloric acid.
These materials break the food down into
even smaller particles, and the resulting
mixture is known as chyme. In addition to
breaking down the particles of food, the hydrochloric acid also kills almost all the bacteria that enter the body with the food. Some
do survive and subsequently begin to live
and multiply in the large intestine. The
stomach also stores food while it is being
partially digested. It then delivers fluid and
partially digested food to the small intestine
in amounts that allow for maximum digestion and absorption.
The last stages of digestion and absorption take place in the small intestine, which
is the longest portion of the digestive tract. Enzymes from the pancreas break down
chyme into monosaccharides, fatty acids,
and amino acids. These substances then
cross the layer of epithelial cells that line the
intestinal wall and enter the blood and
lymph, the watery fluid in the lymph vessels.
A small volume of water, minerals, and
undigested material passes into the large intestine. This material is temporarily stored
and acted upon by the intestinal bacteria.
The large intestine concentrates the material by removing water. The concentrated
material is then eliminated from the body
through defecation when the rectum becomes distended. The eliminated material is
called feces and consists of a small amount
of food that was not digested or absorbed,
toxins, cast-off cells, and bacteria, which
contribute to the bulk of the feces.
- HOW TOXINS ENTER THE GI TRACT
- Toxins arrive in the stomach after being ingested in food or water, or being breathed in
through the nose or mouth and swallowed.
The absorption of toxins in the stomach depends on the amount ingested, as well as the
degree of lipid or water solubility, degree of
ionization, molecular size, and pH of the
toxin. Digestive enzymes, hydrochloric acid,
and bile acids also affect the absorption and metabolism of toxins.
The intestines are exposed to bacteria,
viruses, yeasts and parasites, food and plant
ingredients, and toxins in food, water, and
the environment. Foreign chemicals may
also be absorbed into the body from the
small and large intestines. To be absorbed,
chemicals must be made soluble before they
come into contact with the intestinal mu-
cosa. Unabsorbed chemicals reach their
highest concentration in the colon (large intestine).
Chemicals are usually absorbed slowly
from the GI tract, but the amount absorbed
depends on how rapidly the chemicals move
through it. The faster a chemical passes
through, the less is absorbed. The degree of
intestinal absorption is also affected by gastric emptying time, intestinal motility, the
size and condition of the surface area of the
small intestine, blood flow to the intestine, diet, genetic factors, and age.
- PROTECTIVE DEVICES
- The GI tract has various defense mechanisms against bacteria, viruses, yeasts, parasites, and chemical toxins. It is protected by
enzymes, mucus, normal intestinal bacteria, intestinal secretions, and the innermost
layer of epithelial cells.
In the intestines, the first barrier to the
absorption of chemicals is the unstirred water layer. This layer of immobile fluid coats
the intestinal mucosa (mucous membrane).
It has a mucus layer and an acid micro layer
that is rich in protons (particles with a positive charge). It acts as a barrier to the chemical penetration of the mucosa. Nonpolar,
lipid-soluble chemicals diffuse through the
unstirred water layer more slowly than they
would penetrate a cell membrane. Pesticides, dyes, and food additives are examples of nonpolar chemicals.
The second barrier is gastrointestinal
mucus, which protects the intestinal mucosa from physical and chemical injury, and
acts as a lubricant. Cells in the esophagus,
stomach, small intestine, and large intestine
all produce mucus. Mucus consists of 95
percent water, with the remainder made up
of salts, proteins, nucleic acids, and mucins.
Mucins, composed of carbohydrates, lipids,
and proteins, give mucus its viscous, gel-like
texture. Mucus is sticky and can trap large
molecules, such as metallic chemicals. It
can also trap parasites and bacteria, and can
bind viruses, helping to eliminate them in the feces.
The third barrier to absorption of chemicals is the small intestine's acid microclimate layer, consisting mostly of protons.
This layer has a 5.9 pH, which is acidic compared to the 7.3 pH of the lumen of the small
intestine, which is mildly alkaline. The acid
microclimate layer may influence the permeability of weak acids and alkalis, by repelling acids and neutralizing alkalis.
The fourth barrier is the concentration of
bacteria in the large intestine or colon. More
than 400 species of bacteria reside in the
colon. Intestinal bacteria metabolize drugs
and other chemicals. However, bacteria may
metabolize chemicals in a manner completely opposite to the body's metabolism,
restoring a xenobiotic to its original form, allowing it to reenter circulation and again become part of the toxic load.
Another defense mechanism is the rapid
shedding of intestinal cells. They are some
of the most actively dividing cells in the body,
with up to 100 cells per hour formed in the
intestines, and billions of cells shed every
day. Metals and lipid-soluble chemicals may
be excreted from the intestines along with the old cells.
- DETOXIFICATION
- Both Phase I and Phase II detoxification systems are found in the GI tract, which is the
second major site of detoxification in the
body. Phase I changes the chemicals so that
Phase II can add a small molecule. The GI tract
contains the same biotransformation enzymes as the liver, but metabolism in the GI
tract is slower than in the liver. Depending
on the composition of the toxin, the GI tract
can transform a xenobiotic to either a less
toxic chemical or a more toxic chemical.
In the stomach, pepsin and hydrochloric
acid can help break down chemicals and toxins. The intestines contain bile acids and
various enzymes, such as proteases, lipases,
and glucuronidases, which can also break down chemicals and toxins.
The mixed-function amine oxidase system is most active in the duodenum, the first
part of the small intestine. Mature enterocytes, the cells lining the intestine, contain
the largest amount of cytochrome P-450 activity. The activity of these Phase I enzymes
decreases from the duodenum to the colon.
Many factors affect the ability of the intestines to metabolize xenobiotics. For example, when people go on starvation or
semi-starvation diets, the activity of many of
the metabolic enzymes decreases. Iron deficiency and selenium deficiency can reduce cytochrome P-450 activity. Cruciferous
plants (cabbage, cauliflower, broccoli) increase the activity of the mixed-function
amine oxidase system. Chemicals can decrease or increase enzyme activity, depending on the type of chemical. Enzyme activity
in a portion of the small intestine called the
jejunum has been found to be lower in females than in males. The very young and the
very old also seem to have less active detoxification enzymes.
The gut itself can act as an organ of excretion for toxins. Cells lining the intestinal
walls can secrete xenobiotics into the intestines. Strong acids and digitalis compounds
are secreted from the bloodstream into the
intestinal lumen, where they are then excreted in the feces.
The liver
The liver is a dome-shaped gland that fits
under the diaphragm, just under the right
ribcage. It is considered a gland because it
secretes bile, and it is the largest gland in the body.
The liver is divided into two major regions, the right and left lobes. The right lobe,
which has three smaller lobes, is larger than
the left, which has two smaller lobes. Each of
the five lobes is composed of compartments called liver lobules.
The central vein passes through the center of each lobule and drains away waste
products from the liver. The cells of the lobule closest to the central vein are known as
centrilobular hepatocytes (liver cells). Cytochrome P-450 is most highly concentrated
in these cells, and detoxification activity is also highest in this area.
On the other side of the liver, the hepatic
artery and portal vein are known as the periportal system. The hepatic artery supplies
oxygen to the liver directly from the heart
and lungs. The cells of the lobule closest to
the hepatic artery have the highest concentration of oxygen in the liver. They also have
the highest concentration of nutrients because the liver is the first organ to receive nutrients absorbed by the GI tract, delivered by
the portal vein. These cells also have the
highest exposure to xenobiotics in the liver,
as well as higher concentrations of glutathione and transaminase enzymes. The levels of these enzymes are tested in the standard blood chemistry test for liver function.
- HOW TOXINS ENTER THE LIVER
- The liver is situated to receive a majority of
the venous blood from the lower body, the
kidneys, the spleen, and the gastrointestinal
tract. Approximately 1500 ml of blood, containing many different toxins, flows through the liver every minute.
The liver is the main organ for biotransformation of chemicals. However, it is susceptible to tissue injury from the toxic effects
of chemicals, and if it becomes overloaded,
can be permanently damaged. Some chemicals are toxic to specific parts of the liver.
- PROTECTIVE DEVICES
- Adequate levels of the conjugation enzymes
needed for Phase II are protective for the liver. They help prevent the buildup of toxic
substances formed as a result of biotransformation during Phase I of detoxification. The
presence of adequate antioxidants to quench
free radicals is also protective for the liver.
Even when 80 percent of the cells of the
liver are damaged, the liver can continue to
function, but with reduced efficiency. It has
the ability to restore and replace these damaged cells, and can recover if the sources of the toxins are removed.
- DETOXIFICATION
- The bulk of toxic substances are detoxified in
the liver. The liver removes chemicals that
have been absorbed into the blood, and excretes them into the bile stored in the gallbladder. Both Phase I and Phase II detoxification processes are active in the cells of the
liver, and the liver's cytochrome P-450 system is the body's first-line site for the detoxification of foreign chemicals.
Over 300 known chemicals can induce
(increase) enzyme system activity in the
liver. These chemicals can lead to more enzymes being present and a faster rate of detoxification. They also increase the amount
of endoplasmic reticulum (membranes in
the cell where detoxification occurs) in the liver.
While some chemicals increase the
liver's metabolic action, others inhibit the
activity of cytochrome P-450 and other detoxification enzymes. Chemicals can cause
inhibition in several ways:
- competition between two or more compounds for the same detoxifying enzymes
- inhibition of enzyme synthesis
- inactivation or destruction of enzymes or the endoplasmic reticulum
- overwhelming of the detoxification enzyme systems
- depletion of necessary cofactors for Phase II
Inhibition of cytochrome P-450 can lead
to the buildup of toxins in the body. For example, theophylline is a drug used to control
asthma and belongs to the same family as
caffeine. It can build up to toxic levels if the
patient is given erythromycin simultaneously, which inhibits the cytochrome P-450
enzyme system from breaking down the theophylline. Erythromycin and antifungals
such as ketoconazole can also inhibit the
breakdown of Seldane, an antihistamine.
Because the resulting high levels of Seldane
can cause heart rhythm disturbances, it has been taken off the market.
The kidneys
The principal excretory organs in all vertebrates, the kidneys lie in the back of the abdominal wall, one on each side of the backbone. They are bean-shaped, and on the
concave side of each one is an area called the
hilus, where the renal (kidney) artery enters
and the renal vein exits. The adrenal glands
sit on top of the kidneys. The kidneys are
also regulatory organs, helping to maintain
homeostasis (physiological balance between all body organs).
Each of the kidneys consists of the outer
cortex and the inner medulla. The cortex receives 85 percent of the total renal blood flow
and is composed of nephrons, which are excretory units. Each kidney has over one million nephrons. Each nephron has three parts:
- the vascular or blood circulation component, composed of interconnected capillaries;
- the glomerulus, the filtering tissues of the kidney; and
- the tubules, small tubes or ducts that reabsorb 98 to 99 percent of the salts and water filtered by the glomerulus, for the body's use. The last tubule, the collecting duct, concentrates the remainder of the fluid as urine.
The nephron's tubular element joins
the ureter, which exits from the same side
of the kidney as the renal vein and artery.
The ureter carries the urine to the bladder, a
balloon-shaped storage chamber. As urine
enters the bladder, its walls of smooth muscle unfold to the volume needed to contain
the urine. When the bladder becomes distended, receptors are stimulated to contract
the bladder. The urine then flows under
voluntary control through the urethra, and out of the body.
Kidneys filter out cellular waste, metabolic waste (mostly breakdown products of
protein metabolism), drugs, and toxins from
the blood. In addition to filtering the blood
and draining wastes, the kidneys eliminate
foreign chemicals from the body, and regulate the body's pH balance, calcium metabolism, electrolyte balance, fluid balance, and
extra cellular volume (circulating fluid outside the cells). The kidneys produce a hormone that stimulates red blood cell production, helps to regulate blood pressure, and
also plays a role in vitamin D metabolism.
- HOW TOXINS ENTER THE KIDNEYS
- The kidneys have an even higher blood flow
than the brain, liver, or heart, and receive 25
percent of the body's total blood volume,
causing high exposure to chemicals carried
in the blood. They reabsorb and redistribute
about 99 percent of the blood volume received, and 0.1 percent of the blood filtered becomes urine.
- PROTECTIVE DEVICES
- An adequate supply of Phase II enzymes is
protective for the kidney, as is the intake of
adequate fluids. Kidney stones, which can
damage the kidneys, can form when there is
too little fluid. Accurate pH control of the
urine is also protective, as kidney stones
tend to form when urine pH is not optimum.
Kidney disease can be quite advanced before it is detected, as the kidneys can lose 80 percent of their function before symptoms appear.
- DETOXIFICATION
- The kidneys excrete chemicals that have
been prepared by Phase II detoxification in
other parts of the body. Phase II converts
lipid-soluble nonpolar substances into more
polar substances. This makes them less fat-soluble and less likely to be reabsorbed by
the kidney tubules. They are then available
for excretion in the urine.
Some chemicals (for example, ammonia) are secreted by the tubules and move
into fluid in the lumen (interior) of the
tubule, where they are then eliminated from
the body in the urine. Tubule cells are also
capable of catabolizing (breaking down) certain organic compounds, which destroys
them even though they are not excreted in the urine.
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