Biological surveillance of

aquatic toxicants

Asima Alim
M.Phil Zoology
Toxicants exert their effects when they interact with
cells. This cellular interaction may occur:
(1) On the surface of the cell
(2) Within the cell
(3) In the underlying tissues and extracellular
(interstitial) space.
Although there are four different types of tissues in the
human body (epithelial, connective, muscle, and nerve),
it is a collection of epithelial cells that forms the
epithelium that covers the surface of the body (i.e.,
skin), and forms the lining of the lumen (or inside
walls) of the respiratory and digestive systems.
• Chemical characteristics of both the toxicant and cell
membrane determine whether any interaction occurs
on the surface of the cell or whether the barrier will
be effective in keeping the toxicant out of the
organism.
• Under normal conditions, the contacts between
adjacent epithelial cells will not permit the passage of
substances. This is due to the presence of occluding
cell junctions, which are formed by intramembranous
proteins arranged to “stitch” the membrane of
adjacent cells together
 Cell Membrane Structure
• The cell membrane is composed of phospholipid
molecules. As the term phospholipid implies, there are two
components to the molecule: phosphates and lipids.
• The phosphate head is a region that is hydrophilic. This
means that this portion of the molecule prefers associating
with water (hydro-, water; philic, attraction for or love of).
• In contrast, the lipid tail is a hydrophobic region, which is
repelled by water. Additionally, this region is said to be
lipophilic, or attractive to lipid-soluble substances
• The membrane is termed semipermeable since
it permits some molecules to move across,
while at the same time stopping or impeding
the progress of other molecules
 Process of Cellular Absorption
• Substances use a number of different passive
(spontaneous) and active (energy-requiring) transport
mechanisms to gain entrance into a cell. The most
commonly used process is simple diffusion.
• In this process the molecule relies on its
concentration gradient to enter the cell. This process
is passive, as opposed to active, since no cellular
energy is used to “power” the toxicant across the cell
membrane.
• Remember, diffusion is the movement of a
substance (in this case a toxicant) from a region of
high concentration into a region of low
concentration and, depending on the direction of
the concentration gradient, substances will
continue to move into or out of a cell until
equilibrium is reached.
• In the absence of a concentration on gradient, no
net movement of substances will occur
• A second process used to cross the cell membrane
is facilitated diffusion. In this process molecules
become bound to specific carrier proteins found on
the outer surface of the cell membrane.
• The molecule is then passed, or passively transported,
by the membrane protein into the cell. The “energy”
for transport is derived from the potential energy
stored in the concentration gradient, not from cell
energy input.
• Facilitated diffusion is a well-known mechanism in
the transport of nutrients, such as glucose, across the
cell membrane.
• Facilitated diffusion is thought to play only a minor
role in the transport of toxicants into the cell;
however, it does serve as an important transport
mechanism for the elimination of toxicants or their
metabolites from the cell
• Third, active transport, as a means to enter the
cell, involves the consumption of produced
energy, such as adenosine triphosphate (ATP).
• Whereas passive and facilitated diffusion make
good use of concentration gradients, active
transport enables the cell to transport molecules
against, or up, their concentration gradient.
• Although not a major route of toxicant entry into
the cell, active transport, like facilitated diffusion,
does play a vital role in the elimination of
toxicants or their metabolic intermediates from a
cell.
• It is impossible for many large molecules and
particulates to go into or leave the cell via passive or
active transport mechanisms. Instead, these
macromolecules enter and exit the cell by two
different processes called endocytosis and exocytosis,
respectively.
• During endocytosis the cell membrane will flow
around and engulf the macromolecules that are in
close proximity to the cell.
• Once engulfed, the particulates, now with its cell
membrane covering, will invaginate or turn inward to
form a vesicle.
• The vesicle will detach from the adjacent cell
membrane and become part of the cytoplasm.
• Phagocytosis (cellular eating) and pinocytosis (cellular
drinking) are two types of endocytosis.
• Phagocytosis, performed by special white blood cells,
is responsible for removing particulates from the small
sacs (alveoli) in the lung.
 Cellular Uptake of Toxicants
• Two features characterize toxicants that make use of
simple diffusion to enter a cell.
• First, they are nonpolar or lipid soluble. Nonpolar
means that they have a neutral molecular charge
distribution, unlike polar molecules, which have a
positive or negative charge.
• And lipid soluble indicates that the toxicant will
dissolve in lipids, such as would be found in the middle
of the phospholipid bilayer.
• Second, they have low molecular weights—that is, they
are small, usually with a molecular weight of less than
600 (MW)
• There is an inverse relationship between the
molecular weight of a chemical and its ability
to move through the cell membrane.
• Typically, a nonpolar, lipid-soluble toxicant
will diffuse across a cell membrane much
more rapidly than a polar, water-soluble
toxicant of the same size.
 Routes of Absorption
• Absorption is the process by which toxicants cross
the epithelial cell barrier.
• Depending on the nature of the toxicant, dose,
duration, and type of exposure, a toxicant may limit
its contact to the outer surface of the epithelial cell
barrier, or cross the cell membrane, enter the cell,
and possibly move completely through the cell and
into the underlying lymphatic or cardiovascular
divisions of the circulatory system
There are three primary routes of absorption:
(1) percutaneous (integumentary system), or
through the skin;
(2) the respiratory system; and
(3) the digestive system.
Under accidental circumstances where there is an
unnatural interruption to the integrity of the
barrier (e.g., lacerations, punctures, chemical or
electrical burns), absorption can also take place in
the exposed tissues found beneath the epithelium,
such as subcutaneous fat and muscle.
• Each route of absorption has its own special type of
epithelial cells that unite to form specific tissues.
These unique cell and tissue characteristics present
the potential toxicant with a different set of structural
and functional features that must be overcome to gain
entrance into the body.
 Percutaneous Route
The integumentary system is the largest organ system in the human
body. Although the skin is the most obvious organ of the
integumentary system, this system also includes hair, fingernails and
toenails, and mammary glands. Skin plays an important role to
(1) Provide a barrier against the entrance of toxicants
(2) Protect against the harmful effects of ultraviolet radiation
(3) Prevent the entrance of microorganisms
(4) Assist in the biotransformation or metabolic detoxification of
toxicants
(5) Eliminate toxicants or their metabolites via sweat or other
glandular secretions
(6) Regulate body temperature
(7) House sensory receptors for temperature, pressure, and pain
• Several routes of absorption are possible through the skin.
The most common is the cutaneous adsorption of a
toxicant followed by passive diffusion through the
epidermis into the dermis where the toxicant might enter a
blood vessel.
• Passage into the dermis is enhanced if the toxicant enters
a sweat gland or hair follicle. Since these structures
originate in the dermis and penetrate through the
epidermis, this route effectively bypasses the protective
barrier provided by the epidermis
• Diffusion is also accelerated when the skin has been
pretreated with organic solvents, such as chloroform
(CHCl3), methanol (CH3OH), or dimethyl sulfoxide
([CH3]2SO). Enhanced epidermal permeability is
thought to result from the removal of extracellular
lipids by these solvents.
• Finally, when toxicants become localized in the
epidermis, local toxicity, rather than systemic
toxicity, is the likely result. This is because the
epidermis is avascular (having no blood vessels).
Without a transport mechanism, toxicants cannot be
distributed to other areas of the body where systemic
toxicity may result.
 Respiratory System Route
• The respiratory system is composed of the nasopharyngeal,
tracheobronchial, and pulmonary anatomical regions . Each
region contributes a unique functional component that
prohibits or limits the ability of toxicants to enter the body.
• In addition to the tissue type previously noted in the
epidermis of the skin (i.e., stratified squamous epithelial
tissue), the lumen of the respiratory system also contains
ciliated columnar epithelium and ciliated cuboidal
epithelium, the appearance of which resembles the names.
• Unlike in skin, the stratified squamous
epithelium in the respiratory system is non
keratinized
• Due to its non keratinized form, the stratified
squamous epithelium in the respiratory system
is less effective in serving as a barrier. Mucus
secreting cells, smooth muscle, cartilage, and
immune cells can be found in specific regions
of the respiratory system.
• The respiratory system, with its close anatomical
and physiological association with the
cardiovascular system, is one of the prime sites for
the absorption and distribution of toxicants.
• The cells lining the lumina of the respiratory
system are highly susceptible to toxicants, both
particulates and gases.
• Pneumocystis, which form the delicate alveoli, are
capable of rapidly transporting toxicants directly
into the pulmonary blood circulation for
distribution to the rest of the body.
 Digestive System Route
• The digestive system includes the mouth, oral cavity,
esophagus, stomach, small intestine, large intestine, rectum,
and anus, as well as accessory organs such as the pancreas and
liver. Four distinct zones are found in the digestive system:
(1) mucosa,
(2) Sub mucosa,
(3) Muscularis, and
(4) serosa.
Depending on the location in the digestive system, the mucosa
lining the lumen can be a tough, non keratinized, stratified
squamous epithelium (as in the mouth and esophagus) or a
simple columnar epithelium (as in the small intestine)
• Which functions well in absorption and secretion.
The mucosa is avascular and in some regions
(small intestine) has numerous projections called
villi, each of which will have about 2,500
microvilli protruding from its surface
• Again, as previously evidenced in the highly
branched alveolar region of the lung, the villi and
microvilli serve to increase the absorptive surface
area of the small intestine.
• Absorption can take place across the mucosal lining
anywhere along the entire length of the digestive
system.
• However, the time food and potential toxicants are in
the mouth and esophagus is usually too short to be a
major site of toxicant entry.
• The stomach, where food may remain for about 2
hours, is the site where mechanical digestion occurs
and where hydrochloric acid (HCl), gastric enzymes,
and bacteria help to chemically break down food
• Most absorption of food and toxicants takes place in
the small intestine. Pinocytosis is one way substances
can enter the systemic circulation via the lymph
vessels, which are abundant in the submucosa that
underlies the mucosa. This route of absorption is not
as direct as it may seem.
• Toxicants must enter and move through the mucosal
epithelium and continue into the submucosa, where
they enter the lymphatic system.
• Lymph is then transported through lymph ducts and
vessels up to the region of the heart, where two large
lymph vessels, the common thoracic duct and right
lymphatic duct, drain into the cardiovascular system
near the aorta.
• The large intestine is the final region of the
digestive system.
• This region lacks villi and is not considered a
major site for absorption of toxicants.
However, this region does function to remove
liquid from chyme (food that is mixed with
digestive “juices” such as HCl and enzymes),
thereby producing the more solid form of
indigestible waste called feces.