|Lecture Notes:: 21 January
© R. Paselk 2008
- I want to give a brief overview of some organismic biology
before we begin our discussion of toxicology. One of the sacrifices
made by organisms when they become multicellular is a loss in
surface area for exchange vs. volume. Thus multicellular organism
must create special organs with large surfaces for exchange of
nutrients, gases etc. Of course these surfaces also allow the
exchange of toxicants. Lets look at the major organ systems involved
in exchanges with the environment:
- We can begin with the gastrointestinal tract:
- Just to put things in perspective we should note that the
gastrointestinal tract is like the hole in a donut - things in
the digestive tract are not inside of your body. Thus,
in the figure the esophagus, the stomach, the small intestine,
the large intestine, the gall bladder, and the worm-like appendage
(appendix) are all segments or dents in the hole in the donut.
All of these organs provide exchange surfaces. The gall bladder
is excretory: it both excretes wastes (including toxics) and
it provides detergents to aid in digesting fats and oils. The
remaining organs will be mostly ingestion. Where a chemical will
enter this system will depend on the relative surface areas,
the nature of the surface, and the conditions in the compartment.
Thus the small intestine is by far the most important absorbing
organ for most things because it is very long, increasing its
relative surface area, but more important, its surface is tremendously
increased by microscopic villi (finger-like projections made
up of many cells), which in turn have microvilli (finger-like
projections from individual cells). Factors such as pH also influence
absorption by changing the polarity of chemicals and making them
more or less soluble in membranes. The pH in the stomach can
be very acidic, for example in carnivores around pH 2, while
the pH of the small intestine is often slightly basic, around
- Next we can look at the respiratory system:
- The respiratory system consists of a long tube, the trachea,
which then branches repeatedly down to the very fine bronchioles
which end in the tiny alveoli (sacs):
- This system provides a tremendous surface area for gas exchange.
Again different parts of this system will be major points for
exchange or damage by different toxins. Here one major factor
is the relative solubility of a toxin in aqueous fluids (very
soluble substances will dissolve early and thus not get far down
the system, localizing damage and/or exchange to the trachea,
low solubility substances may reach all of the way to the alveoli
where most exchange will take place due to the larger surface
for interaction and lesser surface coating). A second factor
for point of action is particle or aerosol size. Larger aerosols/particles
will be trapped in the trachea, whereas very fine particles/aerosols
may reach down into the bronchioles etc.
- A third major system for exchange and potential damage is
the urinary system. This system is used for excretion. It is
subject to high exposure to some toxins because so much of the
blood circulation passes through the kidneys, and of course the
kidneys then concentrate various substance for excretion. The
kidneys also have a high level of metabolic competence like the
liver, and thus toxify some compounds. The overall metabolic
effect of the kidneys is relatively low however, because of the
large difference in size between the liver and the kidneys. Thus
most metabolic transformation will take place in the liver.
- Finally, a very obvious surface for exchange is the skin.
Note that the outer "horny" layer of the skin is dead,
so exposure is only a problem if this outer layer is penetrated.
As aqueous organisms exposed to a largely aqueous environment,
the skins outer layer is designed to be most resistant to polar
molecules. Thus the skins (or outer surfaces) of most organisms
are rich in lipids (oils and waxes) which are excellent barriers
to aqueous solutions and polar molecules. On the other hand,
non-polar molecules, like the oily toxin of poison oak, penetrate
easily. However, these toxins are then mostly confined to the
skin itself, since they are not soluble in the aqueous environment
of the body itself! So there is, in a sense a double barrier.
Cells and Cell Compartments
Look at handout/overhead on compartmentation of cells.
- Eukaryotes differ from prokaryotes in having a nucleus and cell organelles (their cells are physically compartmentalized). As a point of reference, an E. coli (bacterial) cell is about the size of a typical mammalian mitochondria.
- Cytosol: Glycolysis and most of gluconeogenesis; Pentose Phosphate shunt; Fatty acid biosynthesis.
- Mitochondria: Kreb's Citric Acid Cycle; Electron transport system and Oxidative Phosphorylation; Fatty acid oxidation; Amino acid catabolism; Interconversion of carbon skeletons.
- Endoplasmic Reticulum: Lipid Synthesis; Steroid synthesis; Phase one detoxification reactions; Biosynthesis and modification of membrane and export proteins.
- Golgi Complex: Further modification of membrane and export proteins.
- Lysosomes: Hydrolytic (digestive) enzyme localization.
- Peroxisomes: Amino acid oxidases, catalase-oxidative degradation reactions.
- Nucleus: DNA replication, synthesis and processing of messenger RNA's.
- Nucleolus: localized region of the nucleus in which ribosomal RNA's are synthesized and processed.
- Plasma Membrane: Active and passive transport systems; receptors and signal processing systems (synthesis of various second messengers etc.).
- Ribosomes: protein synthesis (associated with ER for membrane and export proteins).
The figures illustrating the various organs were scanned from:
Worthington Hooker and J.A. Sewall. Hooker's New Physiology.
Sheldon & Co., NY (1884).
Last modified 22 January 2010
© RA Paselk 2001