Subjects and Topics in Basic Medical Science-A Imhotep Virtual Medical School Primer

Subjects and Topics in Basic
Medical Science
A Imhotep Virtual Medical School Primer
Compiled and Edited by Marc Imhotep Cray, M.D.

Contents
Articles
Anatomy 1
Embryology 3
Biochemistry 6
Histology 14
Epidemiology 20
Biostatistics 31
Molecular biology 34
Genetics 39
Cell biology 55
Endocrinology 60
General pathology 65
Immunology 67
Microbiology 71
Physiology 76
Pathophysiology 78
Pathology 80
Pathogenesis 85
Neuroscience 85
Pharmacology 93
Toxicology 98
Medicine 100
Medical history 114
Chief complaint 116
History of the present illness 117
Past medical history 119
Review of systems 121
Biological system 123
Family history (medicine) 124
List of childhood diseases and disorders 125
Social history (medicine) 127
Allergy 128
Doctor-patient relationship 142
Differential diagnosis 146
Symptom 148
Compiled and Edited by Marc Imhotep Cray , M.D.

Medical sign 149
Physical examination 154
References
Article Sources and Contributors 157
Image Sources, Licenses and Contributors 163
Article Licenses
License 165
Subjects and Topics in Basic Medical Science A Imhotep Virtual Medical School Primer

Anatomy 1
Anatomy
Anatomy lesson carried out in Java, Dutch East
Indies, date unknown.
Anatomy (from the Greek ἀνατομία anatomia, from ἀνατέμνειν ana:
separate, apart from, and temnein, to cut up, cut open) is a branch of
biology and medicine that is the consideration of the structure of living
things. It is a general term that includes human anatomy, animal
anatomy (zootomy) and plant anatomy (phytotomy). In some of its
facets anatomy is closely related to embryology, comparative anatomy
and comparative embryology,
[1]
through common roots in evolution.
Anatomy is subdivided into gross anatomy (or macroscopic anatomy)
and microscopic anatomy.[1]
Gross anatomy (also called topographical
anatomy, regional anatomy, or anthropotomy) is the study of
anatomical structures that can be seen by unaided vision with the naked
eye.
[1]
Microscopic anatomy is the study of minute anatomical structures assisted with microscopes, which includes
histology (the study of the organization of tissues),
[1]
and cytology (the study of cells).
The history of anatomy has been characterized, over time, by a continually developing understanding of the
functions of organs and structures in the body. Methods have also improved dramatically, advancing from
examination of animals through dissection of cadavers (dead human bodies) to technologically complex techniques
developed in the 20th century including X-ray, ultrasound, and MRI imaging.
Anatomy should not be confused with anatomical pathology (also called morbid anatomy or histopathology), which
is the study of the gross and microscopic appearances of diseased organs.
Superficial anatomy
Superficial anatomy or surface anatomy is important in anatomy being the study of anatomical landmarks that can be
readily seen from the contours or the surface of the body.
[1]
With knowledge of superficial anatomy, physicians or
veterinary surgeons gauge the position and anatomy of the associated deeper structures. Superficial is a directional
term that indicates one structure is located more externally than another, or closer to the surface of the body.
Human anatomy
Para-sagittal MRI scan of the head
Human anatomy, including gross human anatomy and histology, is primarily
the scientific study of the morphology of the adult human body.
[1]
Generally, students of certain biological sciences, paramedics, prosthetists
and orthotists, physiotherapists, occupational therapy, nurses, and medical
students learn gross anatomy and microscopic anatomy from anatomical
models, skeletons, textbooks, diagrams, photographs, lectures and tutorials.
The study of microscopic anatomy (or histology) can be aided by practical
experience examining histological preparations (or slides) under a
microscope; and in addition, medical students generally also learn gross
anatomy with practical experience of dissection and inspection of cadavers
(dead human bodies).
Human anatomy, physiology and biochemistry are complementary basic medical sciences, which are generally
taught to medical students in their first

Anatomy 2
An X-ray of a human chest.
Human heart and lungs, from an older
edition of Gray's Anatomy.
year at medical school. Human anatomy can be taught regionally or
systemically;
[1]
that is, respectively, studying anatomy by bodily regions such
as the head and chest, or studying by specific systems, such as the nervous or
respiratory systems. The major anatomy textbook, Gray's Anatomy, has
recently been reorganized from a systems format to a regional format,[2] [3]
in
line with modern teaching methods. A thorough working knowledge of
anatomy is required by all medical doctors, especially surgeons, and doctors
working in some diagnostic specialities, such as histopathology and
radiology.
Academic human anatomists are usually employed by universities, medical
schools or teaching hospitals. They are often involved in teaching anatomy,
and research into certain systems, organs, tissues or cells.
Other branches
• Comparative anatomy relates to the comparison of anatomical structures
(both gross and microscopic) in different animals.
[1]
• Anthropological anatomy or physical anthropology relates to the
comparison of the anatomy of different races of humans.
• Artistic anatomy relates to anatomic studies for artistic reasons.
Notes
[1] "Introduction page, "Anatomy of the Human Body". Henry Gray. 20th edition. 1918" (http://www.bartleby.com/107/1.html). . Retrieved
19 March 2007.
[2] "Publisher's page for Gray's Anatomy. 39th edition (UK). 2004. ISBN 0-443-07168-3" (http://web.archive.org/web/20071012104507/
http://intl.elsevierhealth.com/catalogue/title.cfm?ISBN=0443071683). Archived from the original (http://www.intl.elsevierhealth.com/
catalogue/title.cfm?ISBN=0443071683) on 2007-10-12. . Retrieved 19 March 2007.
[3] "Publisher's page for Gray's Anatomy. 39th edition (US). 2004. ISBN 0-443-07168-3" (http://web.archive.org/web/20070209134753/
http://www.us.elsevierhealth.com/product.jsp?isbn=0443071683). Archived from the original (http://www.us.elsevierhealth.com/
product.jsp?isbn=0443071683) on 9 February 2007. . Retrieved 19 March 2007.
References
• "Anatomy of the Human Body". 20th edition. 1918. Henry Gray (http://www.bartleby.com/107/)
External links
• Anatomy Mnemonics (http://www.lifehugger.com/anatomy) Mnemonics in Anatomy.
• Journal - Journal of Anatomy (http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1469-7580)*
• Anatomy (http://www.bbc.co.uk/programmes/p005488j) on In Our Time at the BBC. ( listen now (http://
www.bbc.co.uk/iplayer/console/p005488j/In_Our_Time_Anatomy))
• Anatomia 1522–1867: Anatomical Plates from the Thomas Fisher Rare Book Library (http://link.library.
utoronto.ca/anatomia/)
• Anatomy of the Human Body (http://www.bartleby.com/107/) Gray, Henry. Philadelphia: Lea & Febiger,
1918
• High-Resolution Cytoarchitectural Primate Brain Atlases (http://brainmaps.org/)
• Anatomy in the 16th century (http://www.bium.univ-paris5.fr/histmed/medica/anatomie.htm#vonseng)
studies and digitized texts by the BIUM (Bibliothèque interuniversitaire de médecine et d'odontologie, Paris)

Anatomy 3
(http://www.bium.parisdescartes.fr) see its digital library Medic@ (http://www.bium.univ-paris5.fr/
histmed/medica.htm).
• 19th Century Anatomy Lesson (http://burkeandhare.com/bhlesson.htm) Animated dissection following Gray's
Anatomy
Embryology
1 - morula, 2 - blastula
1 - blastula, 2 - gastrula with blastopore; orange - ectoderm, red -
endoderm.
Embryology (from Greek ἔμβρυον, embryon, "unborn,
embryo"; and -λογία, -logia) is a science which is about
the development of an embryo from the fertilization of
the ovum to the fetus stage. After cleavage, the dividing
cells, or morula, becomes a hollow ball, or blastula,
which develops a hole or pore at one end.
In bilateral animals, the blastula develops in one of two
ways that divides the whole animal kingdom into two
halves (see: Embryological origins of the mouth and
anus). If in the blastula the first pore (blastopore)
becomes the mouth of the animal, it is a protostome; if
the first pore becomes the anus then it is a deuterostome.
The protostomes include most invertebrate animals, such
as insects, worms and molluscs, while the deuterostomes
include the vertebrates. In due course, the blastula
changes into a more differentiated structure called the
gastrula.
The gastrula with its blastopore soon develops three
distinct layers of cells (the germ layers) from which all
the bodily organs and tissues then develop:
• The innermost layer, or endoderm, gives rise to the
digestive organs, lungs and bladder.
• The middle layer, or mesoderm, gives rise to the
muscles, skeleton and blood system.
• The outer layer of cells, or ectoderm, gives rise to the nervous system and skin.
In humans, the term embryo refers to the ball of dividing cells from the moment the zygote implants itself in the
uterus wall until the end of the eighth week after conception. Beyond the eighth week, the developing human is then
called a fetus. Embryos in many species often appear similar to one another in early developmental stages. The
reason for this similarity is because species have a shared evolutionary history. These similarities among species are
called homologous structures, which are structures that have the same or similar function and mechanism having
evolved from a common ancestor.

Embryology 4
History
Human embryo at six weeks
gestational age
Histological film 10 day mouse embryo
Beetle larvae
As recently as the 18th century, the prevailing notion in human embryology
was preformation: the idea that semen contains an embryo — a preformed,
miniature infant, or "homunculus" — that simply becomes larger during
development. The competing explanation of embryonic development was
epigenesis, originally proposed 2,000 years earlier by Aristotle. According to
epigenesis, the form of an animal emerges gradually from a relatively
formless egg. As microscopy improved during the 19th century, biologists
could see that embryos took shape in a series of progressive steps, and
epigenesis displaced preformation as the favored explanation among
embryologists.
[1]
Modern embryological pioneers include Karl Ernst von Baer, Charles
Darwin, Ernst Haeckel, J.B.S. Haldane, and Joseph Needham, while much
early embryology came from the work of Aristotle and the great Italian
anatomists: Aldrovandi, Aranzio, Leonardo da Vinci, Marcello Malpighi,
Gabriele Falloppio, Girolamo Cardano, Emilio Parisano, Fortunio Liceti,
Stefano Lorenzini, Spallanzani, Enrico Sertoli, Mauro Rusconi, etc.
[2]
Other
important contributors include William Harvey, Kaspar Friedrich Wolff,
Heinz Christian Pander, August Weismann, Gavin de Beer, Ernest Everett
Just, and Edward B. Lewis.
After the 1950s, with the DNA helical structure being unravelled and the
increasing knowledge in the field of molecular biology, developmental
biology emerged as a field of study which attempts to correlate the genes with
morphological change, and so tries to determine which genes are responsible
for each morphological change that takes place in an embryo, and how these
genes are regulated.
Vertebrate and invertebrate embryology
Many principles of embryology apply to both invertebrate animals as well as
to vertebrates.
[3]
Therefore, the study of invertebrate embryology has
advanced the study of vertebrate embryology. However, there are many
differences as well. For example, numerous invertebrate species release a
larva before development is complete; at the end of the larval period, an
animal for the first time comes to resemble an adult similar to its parent or
parents. Although invertebrate embryology is similar in some ways for
different invertebrate animals, there are also countless variations. For
instance, while spiders proceed directly from egg to adult form many insects
develop through at least one larval stage
Modern embryology research
Currently, embryology has become an important research area for studying
the genetic control of the development process (e.g. morphogens), its link to cell signalling, its importance for the
study of certain diseases and mutations and in links to stem cell research.

Embryology 5
References
[1] Campbell et al. (p. 987)
[2] Massimo De Felici, Gregorio Siracus, The rise of embryology in Italy: from the Renaissance to the early 20th Century, (http://www.ijdb.
ehu.es/fullaccess/fulltext.0009/ft515.pdf) Int. J. Dev. Biol. 44: 515-521 (2000).
[3] Parker, Sybil. "Invertebrate Embryology," McGraw-Hill Encyclopedia of Science & Technology (http://books.google.com/
books?vid=ISBN0079115047&id=CMC32Rmo9tYC&q="invertebrate+embryology"+and+"mcgraw-hill"&dq="invertebrate+
embryology"+and+"mcgraw-hill"&pgis=1) (McGraw-Hill 1997).
Embryology - History of embryology as a science." Science Encyclopedia. Web. 06 Nov. 2009.
<http://science.jrank.org/pages/2452/Embryology.html>.
"Germ layer." Encyclopædia Britannica. 2009. Encyclopædia Britannica Online. 06 Nov. 2009
<http://www.britannica.com/EBchecked/topic/230597/germ-layer>.
Further reading
• Apostoli, Pietro; Catalani, Simona (2011). "Chapter 11. Metal Ions Affecting Reproduction and Development". In
Astrid Sigel, Helmut Sigel and Roland K. O. Sigel. Metal Ions in Toxicology. Metal Ions in Life Sciences. 8. RSC
Publishing. pp. 263-303. doi:10.1039/9781849732116-00263.
• Scott F. Gilbert. Developmental Biology. Sinauer, 2003. ISBN 0-87893-258-5.
• Lewis Wolpert. Principles of Development. Oxford University Press, 2006. ISBN 0-19-927536-X.
External links
• Indiana University's Human Embryology Animations (http://www.indiana.edu/~anat550/embryo_main/index.
html)
• What is a human admixed embryo? (http://www.cambridgenetwork.co.uk/views/biolines)
• UNSW Embryology (http://embryology.med.unsw.edu.au/) | UNSW Embryology (http://php.med.unsw.
edu.au/embryology/index.php?title=Main_Page) Large resource of information and media
• Definition of embryo according to Webster (http://www2.merriam-webster.com/cgi-bin/
mwmednlm?book=Medical&va=embryo)

Biochemistry 6
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms,
including, but not limited to, living matter. Biochemistry governs all living organisms and living processes. By
controlling information flow through biochemical signalling and the flow of chemical energy through metabolism,
biochemical processes give rise to the incredible complexity of life. Much of biochemistry deals with the structures
and functions of cellular components such as proteins, carbohydrates, lipids, nucleic acids and other biomolecules
although increasingly processes rather than individual molecules are the main focus. Over the last 40 years
biochemistry has become so successful at explaining living processes that now almost all areas of the life sciences
from botany to medicine are engaged in biochemical research. Today the main focus of pure biochemistry is in
understanding how biological molecules give rise to the processes that occur within living cells which in turn relates
greatly to the study and understanding of whole organisms.
Among the vast number of different biomolecules, many are complex and large molecules (called biopolymers),
which are composed of similar repeating subunits (called monomers). Each class of polymeric biomolecule has a
different set of subunit types.
[1]
For example, a protein is a polymer whose subunits are selected from a set of 20 or
more amino acids. Biochemistry studies the chemical properties of important biological molecules, like proteins, and
in particular the chemistry of enzyme-catalyzed reactions.
The biochemistry of cell metabolism and the endocrine system has been extensively described. Other areas of
biochemistry include the genetic code (DNA, RNA), protein synthesis, cell membrane transport, and signal
transduction.
History
It once was generally believed that life and its materials had some essential property or substance distinct from any
found in non-living matter, and it was thought that only living beings could produce the molecules of life. Then, in
1828, Friedrich Wöhler published a paper on the synthesis of urea, proving that organic compounds can be created
artificially.
[2] [3]
The dawn of biochemistry may have been the discovery of the first enzyme, diastase (today called amylase), in 1833
by Anselme Payen. Eduard Buchner contributed the first demonstration of a complex biochemical process outside of
a cell in 1896: alcoholic fermentation in cell extracts of yeast. Although the term “biochemistry” seems to have been
first used in 1882, it is generally accepted that the formal coinage of biochemistry occurred in 1903 by Carl Neuberg,
a German chemist. Previously, this area would have been referred to as physiological chemistry. Since then,
biochemistry has advanced, especially since the mid-20th century, with the development of new techniques such as
chromatography, X-ray diffraction, dual polarisation interferometry, NMR spectroscopy, radioisotopic labeling,
electron microscopy and molecular dynamics simulations. These techniques allowed for the discovery and detailed
analysis of many molecules and metabolic pathways of the cell, such as glycolysis and the Krebs cycle (citric acid
cycle).
Another significant historic event in biochemistry is the discovery of the gene and its role in the transfer of
information in the cell. This part of biochemistry is often called molecular biology. In the 1950s, James D. Watson,
Francis Crick, Rosalind Franklin, and Maurice Wilkins were instrumental in solving DNA structure and suggesting
its relationship with genetic transfer of information. In 1958, George Beadle and Edward Tatum received the Nobel
Prize for work in fungi showing that one gene produces one enzyme. In 1988, Colin Pitchfork was the first person
convicted of murder with DNA evidence, which led to growth of forensic science. More recently, Andrew Z. Fire
and Craig C. Mello received the 2006 Nobel Prize for discovering the role of RNA interference (RNAi), in the
silencing of gene expression.

Biochemistry 7
Today, there are three main types of biochemistry. Plant biochemistry involves the study of the biochemistry of
autotrophic organisms such as photosynthesis and other plant specific biochemical processes. General biochemistry
encompasses both plant and animal biochemistry. Human/medical/medicinal biochemistry focuses on the
biochemistry of humans and medical illnesses.
Biomolecules
The four main classes of molecules in biochemistry are carbohydrates, lipids, proteins, and nucleic acids. Many
biological molecules are polymers: in this terminology, monomers are relatively small micromolecules that are
linked together to create large macromolecules, which are known as polymers. When monomers are linked together
to synthesize a biological polymer, they undergo a process called dehydration synthesis.
Carbohydrates
A molecule of sucrose (glucose +
fructose), a disaccharide.
Carbohydrates are made from monomers called monosaccharides. Some of these
monosaccharides include glucose (C
6
H
12
O
6
), fructose (C
6
H
12
O
6
), and deoxyribose
(C
5
H
10
O
4
). When two monosaccharides undergo dehydration synthesis, water is
produced, as two hydrogen atoms and one oxygen atom are lost from the two
monosaccharides' hydroxyl group.
Lipids
A triglyceride with a glycerol molecule
on the left and three fatty acids coming
off it.
Lipids are usually made from one molecule of glycerol combined with other
molecules. In triglycerides, the main group of bulk lipids, there is one
molecule of glycerol and three fatty acids. Fatty acids are considered the
monomer in that case, and may be saturated (no double bonds in the carbon
chain) or unsaturated (one or more double bonds in the carbon chain).
Lipids, especially phospholipids, are also used in various pharmaceutical
products, either as co-solubilisers (e.g. in parenteral infusions) or else as drug
carrier components (e.g. in a liposome or transfersome).
Proteins
The general structure of an
α-amino acid, with the
amino group on the left and
the carboxyl group on the
right.
Proteins are very large molecules – macro-biopolymers – made from monomers called
amino acids. There are 20 standard amino acids, each containing a carboxyl group, an
amino group, and a side chain (known as an "R" group). The "R" group is what makes
each amino acid different, and the properties of the side chains greatly influence the
overall three-dimensional conformation of a protein. When amino acids combine, they
form a special bond called a peptide bond through dehydration synthesis, and become a
polypeptide, or protein.
To determine if two proteins are related or in other words to decide whether they are
homologous or not, scientists use sequence-comparison methods. Methods like Sequence
Alignments and Structural Alignments are powerful tools that help scientist identify
homologies between related molecules. The relevance of finding homologies among proteins goes beyond forming
an evolutionary pattern of protein families. By finding how similar two protein sequences are, we acquire knowledge
about their structure and therefore their function.

Biochemistry 8
Nucleic acids
The structure of deoxyribonucleic acid (DNA), the
picture shows the monomers being put together.
Nucleic acids are the molecules that make up DNA, an extremely
important substance which all cellular organisms use to store their
genetic information. The most common nucleic acids are
deoxyribonucleic acid and ribonucleic acid. Their monomers are
called nucleotides. The most common nucleotides are Adenine,
Cytosine, Guanine, Thymine, and Uracil. Adenine binds with
thymine and uracil; Thymine only binds with Adenine; and
Cytosine and Guanine can only bind with each other.
Carbohydrates
The function of carbohydrates includes energy storage and
providing structure. Sugars are carbohydrates, but not all
carbohydrates are sugars. There are more carbohydrates on Earth
than any other known type of biomolecule; they are used to store
energy and genetic information, as well as play important roles in
cell to cell interactions and communications.
Monosaccharides
Glucose
The simplest type of carbohydrate is a monosaccharide, which among
other properties contains carbon, hydrogen, and oxygen, mostly in a
ratio of 1:2:1 (generalized formula C
n
H
2n
O
n
, where n is at least 3).
Glucose, one of the most important carbohydrates, is an example of a
monosaccharide. So is fructose, the sugar commonly associated with
the sweet taste of fruits.
[4] [a]
Some carbohydrates (especially after
condensation to oligo- and polysaccharides) contain less carbon
relative to H and O, which still are present in 2:1 (H:O) ratio.
Monosaccharides can be grouped into aldoses (having an aldehyde group at the end of the chain, e. g. glucose) and
ketoses (having a keto group in their chain; e. g. fructose). Both aldoses and ketoses occur in an equilibrium (starting
with chain lengths of C4) cyclic forms. These are generated by bond formation between one of the hydroxyl groups
of the sugar chain with the carbon of the aldehyde or keto group to form a hemiacetal bond. This leads to saturated
five-membered (in furanoses) or six-membered (in pyranoses) heterocyclic rings containing one O as heteroatom.
Disaccharides
Sucrose: ordinary table sugar and probably the
most familiar carbohydrate.
Two monosaccharides can be joined together using dehydration
synthesis, in which a hydrogen atom is removed from the end of one
molecule and a hydroxyl group (—OH) is removed from the other; the
remaining residues are then attached at the sites from which the atoms
were removed. The H—OH or H
2
O is then released as a molecule of
water, hence the term dehydration. The new molecule, consisting of
two monosaccharides, is called a disaccharide and is conjoined
together by a glycosidic or ether bond. The reverse reaction can also

Biochemistry 9
occur, using a molecule of water to split up a disaccharide and break the glycosidic bond; this is termed hydrolysis.
The most well-known disaccharide is sucrose, ordinary sugar (in scientific contexts, called table sugar or cane sugar
to differentiate it from other sugars). Sucrose consists of a glucose molecule and a fructose molecule joined together.
Another important disaccharide is lactose, consisting of a glucose molecule and a galactose molecule. As most
humans age, the production of lactase, the enzyme that hydrolyzes lactose back into glucose and galactose, typically
decreases. This results in lactase deficiency, also called lactose intolerance.
Sugar polymers are characterised by having reducing or non-reducing ends. A reducing end of a carbohydrate is a
carbon atom which can be in equilibrium with the open-chain aldehyde or keto form. If the joining of monomers
takes place at such a carbon atom, the free hydroxy group of the pyranose or furanose form is exchanged with an
OH-side chain of another sugar, yielding a full acetal. This prevents opening of the chain to the aldehyde or keto
form and renders the modified residue non-reducing. Lactose contains a reducing end at its glucose moiety, whereas
the galactose moiety form a full acetal with the C4-OH group of glucose. Saccharose does not have a reducing end
because of full acetal formation between the aldehyde carbon of glucose (C1) and the keto carbon of fructose (C2).
Oligosaccharides and polysaccharides
Cellulose as polymer of β-D-glucose
When a few (around three to six) monosaccharides are joined together,
it is called an oligosaccharide (oligo- meaning "few"). These
molecules tend to be used as markers and signals, as well as having
some other uses. Many monosaccharides joined together make a
polysaccharide. They can be joined together in one long linear chain,
or they may be branched. Two of the most common polysaccharides
are cellulose and glycogen, both consisting of repeating glucose
monomers.
• Cellulose is made by plants and is an important structural component of their cell walls. Humans can neither
manufacture nor digest it.
• Glycogen, on the other hand, is an animal carbohydrate; humans and other animals use it as a form of energy
storage.
Use of carbohydrates as an energy source
Glucose is the major energy source in most life forms. For instance, polysaccharides are broken down into their
monomers (glycogen phosphorylase removes glucose residues from glycogen). Disaccharides like lactose or sucrose
are cleaved into their two component monosaccharides.
Glycolysis (anaerobic)
Glucose is mainly metabolized by a very important ten-step pathway called glycolysis, the net result of which is to
break down one molecule of glucose into two molecules of pyruvate; this also produces a net two molecules of ATP,
the energy currency of cells, along with two reducing equivalents in the form of converting NAD
+
to NADH. This
does not require oxygen; if no oxygen is available (or the cell cannot use oxygen), the NAD is restored by converting
the pyruvate to lactate (lactic acid) (e. g. in humans) or to ethanol plus carbon dioxide (e. g. in yeast). Other
monosaccharides like galactose and fructose can be converted into intermediates of the glycolytic pathway.

Biochemistry 10
Aerobic
In aerobic cells with sufficient oxygen, like most human cells, the pyruvate is further metabolized. It is irreversibly
converted to acetyl-CoA, giving off one carbon atom as the waste product carbon dioxide, generating another
reducing equivalent as NADH. The two molecules acetyl-CoA (from one molecule of glucose) then enter the citric
acid cycle, producing two more molecules of ATP, six more NADH molecules and two reduced (ubi)quinones (via
FADH
2
as enzyme-bound cofactor), and releasing the remaining carbon atoms as carbon dioxide. The produced
NADH and quinol molecules then feed into the enzyme complexes of the respiratory chain, an electron transport
system transferring the electrons ultimately to oxygen and conserving the released energy in the form of a proton
gradient over a membrane (inner mitochondrial membrane in eukaryotes). Thereby, oxygen is reduced to water and
the original electron acceptors NAD
+
and quinone are regenerated. This is why humans breathe in oxygen and
breathe out carbon dioxide. The energy released from transferring the electrons from high-energy states in NADH
and quinol is conserved first as proton gradient and converted to ATP via ATP synthase. This generates an additional
28 molecules of ATP (24 from the 8 NADH + 4 from the 2 quinols), totaling to 32 molecules of ATP conserved per
degraded glucose (two from glycolysis + two from the citrate cycle). It is clear that using oxygen to completely
oxidize glucose provides an organism with far more energy than any oxygen-independent metabolic feature, and this
is thought to be the reason why complex life appeared only after Earth's atmosphere accumulated large amounts of
oxygen.
Gluconeogenesis
In vertebrates, vigorously contracting skeletal muscles (during weightlifting or sprinting, for example) do not receive
enough oxygen to meet the energy demand, and so they shift to anaerobic metabolism, converting glucose to lactate.
The liver regenerates the glucose, using a process called gluconeogenesis. This process is not quite the opposite of
glycolysis, and actually requires three times the amount of energy gained from glycolysis (six molecules of ATP are
used, compared to the two gained in glycolysis). Analogous to the above reactions, the glucose produced can then
undergo glycolysis in tissues that need energy, be stored as glycogen (or starch in plants), or be converted to other
monosaccharides or joined into di- or oligosaccharides. The combined pathways of glycolysis during exercise,
lactate's crossing via the bloodstream to the liver, subsequent gluconeogenesis and release of glucose into the
bloodstream is called the Cori cycle.
Proteins
A schematic of hemoglobin. The red and
blue ribbons represent the protein globin;
the green structures are the heme groups.
Like carbohydrates, some proteins perform largely structural roles. For
instance, movements of the proteins actin and myosin ultimately are
responsible for the contraction of skeletal muscle. One property many
proteins have is that they specifically bind to a certain molecule or class of
molecules—they may be extremely selective in what they bind. Antibodies
are an example of proteins that attach to one specific type of molecule. In
fact, the enzyme-linked immunosorbent assay (ELISA), which uses
antibodies, is currently one of the most sensitive tests modern medicine uses
to detect various biomolecules. Probably the most important proteins,
however, are the enzymes. These molecules recognize specific reactant
molecules called substrates; they then catalyze the reaction between them. By
lowering the activation energy, the enzyme speeds up that reaction by a rate
of 10
11
or more: a reaction that would normally take over 3,000 years to
complete spontaneously might take less than a second with an enzyme. The enzyme itself is not used up in the
process, and is free to catalyze the same reaction with a new set of substrates. Using various modifiers, the activity of
the enzyme can be regulated, enabling control of the biochemistry of the cell as a whole.

Biochemistry 11
In essence, proteins are chains of amino acids. An amino acid consists of a carbon atom bound to four groups. One is
an amino group, —NH
2
, and one is a carboxylic acid group, —COOH (although these exist as —NH
3
+
and —COO
−
under physiologic conditions). The third is a simple hydrogen atom. The fourth is commonly denoted "—R" and is
different for each amino acid. There are twenty standard amino acids. Some of these have functions by themselves or
in a modified form; for instance, glutamate functions as an important neurotransmitter.
Generic amino acids (1) in neutral form, (2) as they exist physiologically, and (3) joined
together as a dipeptide.
Amino acids can be joined together via
a peptide bond. In this dehydration
synthesis, a water molecule is removed
and the peptide bond connects the
nitrogen of one amino acid's amino
group to the carbon of the other's
carboxylic acid group. The resulting
molecule is called a dipeptide, and
short stretches of amino acids (usually,
fewer than thirty) are called peptides or polypeptides. Longer stretches merit the title proteins. As an example, the
important blood serum protein albumin contains 585 amino acid residues.
The structure of proteins is traditionally described in a hierarchy of four levels. The primary structure of a protein
simply consists of its linear sequence of amino acids; for instance,
"alanine-glycine-tryptophan-serine-glutamate-asparagine-glycine-lysine-…". Secondary structure is concerned with
local morphology (morphology being the study of structure). Some combinations of amino acids will tend to curl up
in a coil called an α-helix or into a sheet called a β-sheet; some α-helixes can be seen in the hemoglobin schematic
above. Tertiary structure is the entire three-dimensional shape of the protein. This shape is determined by the
sequence of amino acids. In fact, a single change can change the entire structure. The alpha chain of hemoglobin
contains 146 amino acid residues; substitution of the glutamate residue at position 6 with a valine residue changes
the behavior of hemoglobin so much that it results in sickle-cell disease. Finally quaternary structure is concerned
with the structure of a protein with multiple peptide subunits, like hemoglobin with its four subunits. Not all proteins
have more than one subunit.
Ingested proteins are usually broken up into single amino acids or dipeptides in the small intestine, and then
absorbed. They can then be joined together to make new proteins. Intermediate products of glycolysis, the citric acid
cycle, and the pentose phosphate pathway can be used to make all twenty amino acids, and most bacteria and plants
possess all the necessary enzymes to synthesize them. Humans and other mammals, however, can only synthesize
half of them. They cannot synthesize isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan,
and valine. These are the essential amino acids, since it is essential to ingest them. Mammals do possess the enzymes
to synthesize alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, and tyrosine, the
nonessential amino acids. While they can synthesize arginine and histidine, they cannot produce it in sufficient
amounts for young, growing animals, and so these are often considered essential amino acids.
If the amino group is removed from an amino acid, it leaves behind a carbon skeleton called an α-keto acid.
Enzymes called transaminases can easily transfer the amino group from one amino acid (making it an α-keto acid) to
another α-keto acid (making it an amino acid). This is important in the biosynthesis of amino acids, as for many of
the pathways, intermediates from other biochemical pathways are converted to the α-keto acid skeleton, and then an
amino group is added, often via transamination. The amino acids may then be linked together to make a protein.
A similar process is used to break down proteins. It is first hydrolyzed into its component amino acids. Free
ammonia (NH
3
), existing as the ammonium ion (NH
4
+
) in blood, is toxic to life forms. A suitable method for
excreting it must therefore exist. Different strategies have evolved in different animals, depending on the animals'
needs. Unicellular organisms, of course, simply release the ammonia into the environment. Similarly, bony fish can
release the ammonia into the water where it is quickly diluted. In general, mammals convert the ammonia into urea,

Biochemistry 12
via the urea cycle.
Lipids
The term lipid comprises a diverse range of molecules and to some extent is a catchall for relatively water-insoluble
or nonpolar compounds of biological origin, including waxes, fatty acids, fatty-acid derived phospholipids,
sphingolipids, glycolipids and terpenoids (e.g. retinoids and steroids). Some lipids are linear aliphatic molecules,
while others have ring structures. Some are aromatic, while others are not. Some are flexible, while others are rigid.
Most lipids have some polar character in addition to being largely nonpolar. Generally, the bulk of their structure is
nonpolar or hydrophobic ("water-fearing"), meaning that it does not interact well with polar solvents like water.
Another part of their structure is polar or hydrophilic ("water-loving") and will tend to associate with polar solvents
like water. This makes them amphiphilic molecules (having both hydrophobic and hydrophilic portions). In the case
of cholesterol, the polar group is a mere -OH (hydroxyl or alcohol). In the case of phospholipids, the polar groups are
considerably larger and more polar, as described below.
Lipids are an integral part of our daily diet. Most oils and milk products that we use for cooking and eating like
butter, cheese, ghee etc., are composed of fats. Vegetable oils are rich in various polyunsaturated fatty acids (PUFA).
Lipid-containing foods undergo digestion within the body and are broken into fatty acids and glycerol, which are the
final degradation products of fats and lipids.
Nucleic acids
A nucleic acid is a complex, high-molecular-weight biochemical macromolecule composed of nucleotide chains that
convey genetic information. The most common nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid
(RNA). Nucleic acids are found in all living cells and viruses. Aside from the genetic material of the cell, nucleic
acids often play a role as second messengers, as well as forming the base molecule for adenosine triphosphate, the
primary energy-carrier molecule found in all living organisms.
Nucleic acid, so called because of its prevalence in cellular nuclei, is the generic name of the family of biopolymers.
The monomers are called nucleotides, and each consists of three components: a nitrogenous heterocyclic base (either
a purine or a pyrimidine), a pentose sugar, and a phosphate group. Different nucleic acid types differ in the specific
sugar found in their chain (e.g. DNA or deoxyribonucleic acid contains 2-deoxyriboses). Also, the nitrogenous bases
possible in the two nucleic acids are different: adenine, cytosine, and guanine occur in both RNA and DNA, while
thymine occurs only in DNA and uracil occurs in RNA.

Biochemistry 13
Relationship to other "molecular-scale" biological sciences
Schematic relationship between biochemistry, genetics and
molecular biology
Researchers in biochemistry use specific techniques
native to biochemistry, but increasingly combine these
with techniques and ideas from genetics, molecular
biology and biophysics. There has never been a
hard-line between these disciplines in terms of content
and technique. Today the terms molecular biology and
biochemistry are nearly interchangeable. The following
figure is a schematic that depicts one possible view of
the relationship between the fields:
• Biochemistry is the study of the chemical substances
and vital processes occurring in living organisms.
Biochemists focus heavily on the role, function, and
structure of biomolecules. The study of the
chemistry behind biological processes and the
synthesis of biologically active molecules are
examples of biochemistry.
• Genetics is the study of the effect of genetic
differences on organisms. Often this can be inferred by the absence of a normal component (e.g. one gene). The
study of "mutants" – organisms with a changed gene that leads to the organism being different with respect to the
so-called "wild type" or normal phenotype. Genetic interactions (epistasis) can often confound simple
interpretations of such "knock-out" or "knock-in" studies.
• Molecular biology is the study of molecular underpinnings of the process of replication, transcription and
translation of the genetic material. The central dogma of molecular biology where genetic material is transcribed
into RNA and then translated into protein, despite being an oversimplified picture of molecular biology, still
provides a good starting point for understanding the field. This picture, however, is undergoing revision in light of
emerging novel roles for RNA.
• Chemical Biology seeks to develop new tools based on small molecules that allow minimal perturbation of
biological systems while providing detailed information about their function. Further, chemical biology employs
biological systems to create non-natural hybrids between biomolecules and synthetic devices (for example
emptied viral capsids that can deliver gene therapy or drug molecules).
Notes
a. It should be noted that fructose is not the only sugar found in fruits. Glucose and sucrose are also found in
varying quantities in various fruits, and indeed sometimes exceed the fructose present. For example, 32 % of the
edible portion of date is glucose, compared with 23.70 % fructose and 8.20 % sucrose. Conversely, peaches contain
more sucrose (6.66 %) than they do fructose (0.93 %) or glucose (1.47 %).
[5]
References
[1] Campbell, Neil A.; Brad Williamson; Robin J. Heyden (2006). Biology: Exploring Life (http://www.phschool.com/el_marketing.html).
Boston, Massachusetts: Pearson Prentice Hall. ISBN 0-13-250882-6. .
[2] Wöhler, F. (1828). "Ueber künstliche Bildung des Harnstoffs". Ann. Phys. Chem. 12: 253–256.
[3] Kauffman, G. B. and Chooljian, S.H. (2001). "Friedrich Wöhler (1800–1882), on the Bicentennial of His Birth". The Chemical Educator 6
(2): 121–133. doi:10.1007/s00897010444a.
[4] Whiting, G.C (1970). "Sugars". In A.C. Hulme. The Biochemistry of Fruits and their Products. Volume 1. London & New York: Academic
Press. pp. 1=31

Biochemistry 14
[5] Whiting, G.C. (1970), p.5
Further reading
• Hunter, Graeme K. (2000). Vital Forces: The Discovery of the Molecular Basis of Life. San Diego: Academic
Press. ISBN 0-12-361810-X. OCLC 162129355 191848148 44187710.
External links
• The Virtual Library of Biochemistry and Cell Biology (http://www.biochemweb.org/)
• Biochemistry, 5th ed. (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=stryer.
TOC&depth=2) Full text of Berg, Tymoczko, and Stryer, courtesy of NCBI.
• Biochemistry, 2nd ed. (http://www.web.virginia.edu/Heidi/home.htm) Full text of Garrett and Grisham.
• Biochemistry Animation (http://www.1lec.com/Biochemistry/) (Narrated Flash animations.)
• SystemsX.ch - The Swiss Initiative in Systems Biology (http://www.systemsX.ch/)
• Biochemistry Online Resources (http://www.icademic.org/97445/Biochemistry/) – Lists of Biochemistry
departments, websites, journals, books and reviews, employment opportunities and events.
biochemical families: prot · nucl · carb (glpr, alco, glys) · lipd (fata/i, phld, strd, gllp, eico) · amac/i · ncbs/i · ttpy/i
Histology
A stained histologic specimen, sandwiched between a glass microscope slide and
coverslip, mounted on the stage of a light microscope.
Histology (compound of the Greek words:
ἱστός "tissue", and -λογία -logia) is the
study of the microscopic anatomy of cells
and tissues of plants and animals. It is
performed by examining a thin slice
(section) of tissue under a light microscope
or electron microscope. The ability to
visualize or differentially identify
microscopic structures is frequently
enhanced through the use of histological
stains. Histology is an essential tool of
biology and medicine.
Histopathology, the microscopic study of
diseased tissue, is an important tool in
anatomical pathology, since accurate
diagnosis of cancer and other diseases
usually requires histopathological examination of samples. Trained medical doctors, frequently board-certified as
pathologists, are the personnel who perform histopathological examination and provide diagnostic information based
on their observations.

Histology 15
Microscopic view of a histologic specimen of human lung tissue stained with
hematoxylin and eosin.
The trained scientists who perform the
preparation of histological sections are
histotechnicians, histology technicians
(HT), histology technologists (HTL),
medical scientists, medical laboratory
technicians, or biomedical scientists. Their
field of study is called histotechnology.
Histology
Fixing
Chemical fixation with formaldehyde or
other chemicals
Chemical fixatives are used to preserve
tissue from degradation, and to maintain the
structure of the cell and of sub-cellular components such as cell organelles (e.g., nucleus, endoplasmic reticulum,
mitochondria). The most common fixative for light microscopy is 10% neutral buffered formalin (4% formaldehyde
in phosphate buffered saline). For electron microscopy, the most commonly used fixative is glutaraldehyde, usually
as a 2.5% solution in phosphate buffered saline. These fixatives preserve tissues or cells mainly by irreversibly
cross-linking proteins. The main action of these aldehyde fixatives is to cross-link amino groups in proteins through
the formation of CH
2
(methylene) linkage, in the case of formaldehyde, or by a C5H10 cross-links in the case of
glutaraldehyde. This process, while preserving the structural integrity of the cells and tissue can damage the
biological functionality of proteins, particularly enzymes, and can also denature them to a certain extent. This can be
detrimental to certain histological techniques. Further fixatives are often used for electron microscopy such as
osmium tetroxide or uranyl acetate
Formalin fixation leads to degradation of mRNA, miRNA and DNA in tissues. However, extraction, amplification
and analysis of these nucleic acids from formalin-fixed, paraffin-embedded tissues is possible using appropriate
protocols.[1]
Frozen section fixation
Frozen section is a rapid way to fix and mount histology sections. It is used in surgical removal of tumors, and allow
rapid determination of margin (that the tumor has been completely removed). It is done using a refrigeration device
called a cryostat. The frozen tissue is sliced using a microtome, and the frozen slices are mounted on a glass slide
and stained the same way as other methods. It is a necessary way to fix tissue for certain stain such as antibody
linked immunofluorescence staining. It can also be used to determine if a tumour is malignant when it is found
incidentally during surgery on a patient.
Processing - dehydration, clearing, and infiltration
The aim of Tissue Processing is to remove water from tissues and replace with a medium that solidifies to allow thin
sections to be cut. Biological tissue must be supported in a hard matrix to allow sufficiently thin sections to be cut,
typically 5 μm (micrometres; 1000 micrometres = 1 mm) thick for light microscopy and 80-100 nm (nanometre;
1,000,000 nanometres = 1 mm) thick for electron microscopy. For light microscopy, paraffin wax is most frequently
used. Since it is immiscible with water, the main constituent of biological tissue, water must first be removed in the
process of dehydration. Samples are transferred through baths of progressively more concentrated ethanol to remove

Histology 16
the water. This is followed by a hydrophobic clearing agent (such as xylene) to remove the alcohol, and finally
molten paraffin wax, the infiltration agent, which replaces the xylene. Paraffin wax does not provide a sufficiently
hard matrix for cutting very thin sections for electron microscopy. Instead, resins are used. Epoxy resins are the most
commonly employed embedding media, but acrylic resins are also used, particularly where immunohistochemistry is
required. Thicker sections (0.35μm to 5μm) of resin-embedded tissue can also be cut for light microscopy. Again, the
immiscibility of most epoxy and acrylic resins with water necessitates the use of dehydration, usually with ethanol.
Embedding
After the tissues have been dehydrated, cleared, and infiltrated with the embedding material, they are ready for
external embedding. During this process the tissue samples are placed into molds along with liquid embedding
material (such as agar, gelatine, or wax) which is then hardened. This is achieved by cooling in the case of paraffin
wax and heating (curing) in the case of the epoxy resins. The acrylic resins are polymerised by heat, ultraviolet light,
or chemical catalysts. The hardened blocks containing the tissue samples are then ready to be sectioned.
Because Formalin-fixed, paraffin-embedded (FFPE) tissues may be stored indefinitely at room temperature, and
nucleic acids (both DNA and RNA) may be recovered from them decades after fixation, FFPE tissues are an
important resource for historical studies in medicine.
Embedding can also be accomplished using frozen, non-fixed tissue in a water-based medium. Pre-frozen tissues are
placed into molds with the liquid embedding material, usually a water-based glycol, OCT, TBS, Cryogel, or resin,
which is then frozen to form hardened blocks.
Sectioning
Sectioning can be done in limited ways. Vertical sectioning perpendicular to the surface of the tissue is the usual
method. Horizontal sectioning is often done in the evaluation of the hair follicles and pilosebaceous units. Tangential
to horizontal sectioning is done in Mohs surgery and in methods of CCPDMA.
For light microscopy, a steel knife mounted in a microtome is used to cut 10-micrometer-thick tissue sections which
are mounted on a glass microscope slide. For transmission electron microscopy, a diamond knife mounted in an
ultramicrotome is used to cut 50-nanometer-thick tissue sections which are mounted on a 3-millimeter-diameter
copper grid. Then the mounted sections are treated with the appropriate stain.
Frozen tissue embedded in a freezing medium is cut on a microtome in a cooled machine called a cryostat.
Staining
Biological tissue has little inherent contrast in either the light or electron microscope. Staining is employed to give
both contrast to the tissue as well as highlighting particular features of interest. Where the underlying mechanistic
chemistry of staining is understood, the term histochemistry is used. Hematoxylin and eosin (H&E stain) is the most
commonly used light microscopical stain in histology and histopathology. Hematoxylin, a basic dye, stains nuclei
blue due to an affinity to nucleic acids in the cell nucleus; eosin, an acidic dye, stains the cytoplasm pink. Uranyl
acetate and lead citrate are commonly used to impart contrast to tissue in the electron microscope.
Special staining: There are hundreds of various other techniques that have been used to selectively stain cells and
cellular components. Other compounds used to color tissue sections include safranin, oil red o, Congo red, fast green
FCF, silver salts, and numerous natural and artificial dyes that were usually originated from the development dyes
for the textile industry.
Histochemistry refers to the science of using chemical reactions between laboratory chemicals and components
within tissue. A commonly performed histochemical technique is the Perls Prussian blue reaction, used to
demonstrate iron deposits in diseases like hemochromatosis.

Histology 17
Histology samples have often been examined by radioactive techniques. In historadiography, a slide (sometimes
stained histochemically) is X-rayed. More commonly, autoradiography is used to visualize the locations to which a
radioactive substance has been transported within the body, such as cells in S phase (undergoing DNA replication)
which incorporate tritiated thymidine, or sites to which radiolabeled nucleic acid probes bind in in situ hybridization.
For autoradiography on a microscopic level, the slide is typically dipped into liquid nuclear tract emulsion, which
dries to form the exposure film. Individual silver grains in the film are visualized with dark field microscopy.
Recently, antibodies have been used to specifically visualize proteins, carbohydrates, and lipids. This process is
called immunohistochemistry, or when the stain is a fluorescent molecule, immunofluorescence. This technique has
greatly increased the ability to identify categories of cells under a microscope. Other advanced techniques, such as
nonradioactive in situ hybridization, can be combined with immunochemistry to identify specific DNA or RNA
molecules with fluorescent probes or tags that can be used for immunofluorescence and enzyme-linked fluorescence
amplification (especially alkaline phosphatase and tyramide signal amplification). Fluorescence microscopy and
confocal microscopy are used to detect fluorescent signals with good intracellular detail. Digital cameras are
increasingly used to capture histological and histopathological image
Common laboratory stains
Stain Common use Nucleus
Cytoplasm
Red blood
cell (RBC)
Collagen
fibers
Specifically stains
Haematoxylin General staining
when paired with
eosin (i.e. H&E)
Blue N/A N/A N/A Nucleic acids—blue ER (endoplasmic
reticulum)—blue
Eosin General staining
when paired with
haematoxylin (i.e.
H&E)
N/A Pink Orange/red Pink Elastic fibers—pink Collagen fibers—pink
Reticular fibers—pink
Toluidine blue General staining Blue Blue Blue Blue Mast cells granules—purple
Masson's
trichrome stain
Connective tissue Black Red/pink Red Blue/green Cartilage—blue/green Muscle fibers—red
Mallory's
trichrome stain
Connective tissue Red Pale red Orange Deep blue Keratin—orange Cartilage—blue Bone
matrix—deep blue Muscle fibers—red
Weigert's elastic
stain
Elastic fibers Blue/black N/A N/A N/A Elastic fibers—blue/black
Heidenhain's
AZAN trichrome
stain
Distinguishing cells
from extracellular
components
Red/purple Pink Red Blue Muscle fibers—red Cartilage—blue Bone
matrix—blue
Silver stain Reticular fibers,
nerve fibers, fungi
N/A N/A N/A N/A Reticular fibers—brown/black Nerve
fibers—brown/black
Wright's stain Blood cells Bluish/purple Bluish/gray Red/pink N/A Neutrophil granules—purple/pink
Eosinophil granules—bright red/orange
Basophil granules—deep purple/violet
Platelet granules—red/purple
Orcein stain Elastic fibres Deep blue [or
crazy red]
N/A Bright red Pink Elastic fibres—dark brown Mast cells
granules—purple Smooth muscle—light
blue
Periodic
acid-Schiff stain
(PAS)
Basement membrane,
localizing
carbohydrates
Blue N/A N/A Pink Glycogen and other
carbohydrates—magenta

Histology 18
Table sourced from Michael H. Ross, Wojciech Pawlina, (2006). Histology: A Text and Atlas. Hagerstown, MD:
Lippincott Williams & Wilkins. ISBN 0-7817-5056-3.
The Nissl method and Golgi's method are useful in identifying neurons.
Alternative techniques
Alternative techniques include cryosection. The tissue is frozen using a cryostat, and cut. Tissue staining methods are
similar to those of wax sections. Plastic embedding is commonly used in the preparation of material for electron
microscopy. Tissues are embedded in epoxy resin. Very thin sections (less than 0.1 micrometer) are cut using
diamond or glass knives. The sections are stained with electron dense stains (uranium and lead) so that they can
possibly be seen with the electron microscope.
History
In the 19th century, histology was an academic discipline in its own right. The 1906 Nobel Prize in Physiology or
Medicine was awarded to histologists Camillo Golgi and Santiago Ramon y Cajal. They had dueling interpretations
of the neural structure of the brain based in differing interpretations of the same images. Cajal won the prize for his
correct theory and Golgi for the staining technique he invented to make it possible.
Histological classification of animal tissues
There are four basic types of tissues: muscle tissue, nervous tissue, connective tissue, and epithelial tissue. All tissue
types are subtypes of these four basic tissue types (for example, blood cells are classified as connective tissue, since
they generally originate inside bone marrow).
• Epithelium: the lining of glands, bowel, skin, and some organs like the liver, lung, and kidney
• Endothelium: the lining of blood and lymphatic vessels
• Mesothelium: the lining of pleural and pericardial spaces
• Mesenchyme: the cells filling the spaces between the organs, including fat, muscle, bone, cartilage, and tendon
cells
• Blood cells: the red and white blood cells, including those found in lymph nodes and spleen
• Neurons: any of the conducting cells of the nervous system
• Germ cells: reproductive cells (spermatozoa in men, oocytes in women)
• Placenta: an organ characteristic of true mammals during pregnancy, joining mother and offspring, providing
endocrine secretion and selective exchange of soluble, but not particulate, blood-borne substances through an
apposition of uterine and trophoblastic vascularised parts
• Stem cells: cells with the ability to develop into different cell types
Note that tissues from plants, fungi, and microorganisms can also be examined histologically. Their structure is very
different from animal tissues.

Histology 19
Related sciences
• Cell biology is the study of living cells, their DNA and RNA and the proteins they express.
• Anatomy is the study of organs visible by the naked eye.
• Morphology studies entire organisms.
Artifacts
Artifacts are structures or features in tissue that interfere with normal histological examination. These are not always
present in normal tissue and can come from outside sources. Artifacts interfere with histology by changing the
tissues appearance and hiding structures. These can be divided into two categories:
Pre-histology
These are features and structures that have being introduced prior to the collection of the tissues. A common example
of these include: ink from tattoos and freckles (melanin) in skin samples.
Post-histology
Artifacts can result from tissue processing. Processing commonly leads to changes like shrinkage, washing out of
particular cellular components, color changes in different tissues types and alterations of the structures in the tissue.
Because these are caused in a laboratory the majority of post histology artifacts can be avoided or removed after
being discovered. A common example is mercury pigment left behind after using Zenker's fixative to fix a section.
Notes
[1] Weiss AT, Delcour NM, Meyer A, Klopfleisch R. (2010). "Efficient and Cost-Effective Extraction of Genomic DNA From Formalin-Fixed
and Paraffin-Embedded Tissues.". Veterinary Pathology 227. PMID 20817894.
References
1. Merck Source (2002). Dorland's Medical Dictionary. Retrieved 2005-01-26.
2. Stedman's Medical Dictionaries (2005). Stedman's Online Medical Dictionary (http://stedmans.com/).
Retrieved 2005-01-26.
3. 4,000‫ﻱ‬online histology images (2007). (http://histology-online.com)
External links
• Histology Protocols (http://www.ihcworld.com/protocol_database.htm)
• Histoweb (http://www.kumc.edu/instruction/medicine/anatomy/histoweb)
• SIU SOM Histology (http://www.siumed.edu/~dking2/index.htm)
• Visual Histology Atlas (http://www.visualhistology.com/Visual_Histology_Atlas/)
• Histology Glossary (http://www.histology-world.com/glossary/glossary1.htm)
• Histology Group of Victoria Incorporated (http://www.hgv.org.au)
• Histology Photomicrographs (http://www.histology-world.com/photoalbum/)
• Virtual Slidebox (http://www.path.uiowa.edu/virtualslidebox)
• Blue Histology (http://www.lab.anhb.uwa.edu.au/mb140/)

Epidemiology 20
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a society. It is the
cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by
identifying risk factors for disease and targets for preventive medicine. Epidemiologists are involved in the design of
studies, collection and statistical analysis of data, and interpretation and dissemination of results (including peer
review and occasional systematic review). Major areas of epidemiologic work include outbreak investigation,
disease surveillance and screening (medicine), biomonitoring, and comparisons of treatment effects such as in
clinical trials. Epidemiologists rely on a number of other scientific disciplines such as biology (to better understand
disease processes), biostatistics (to make efficient use of the data and draw appropriate conclusions), and exposure
assessment and social science disciplines (to better understand proximate and distal risk factors, and their
measurement).
Etymology
Epidemiology, literally meaning "the study of what is upon the people", is derived from Greek epi, meaning "upon,
among", demos, meaning "people, district", and logos, meaning "study, word, discourse", suggesting that it applies
only to human populations. However, the term is widely used in studies of zoological populations (veterinary
epidemiology), although the term 'epizoology' is available, and it has also been applied to studies of plant
populations (botanical epidemiology).
[1]
The distinction between 'epidemic' and 'endemic' was first drawn by Hippocrates,
[2]
to distinguish between diseases
that are 'visited upon' a population (epidemic) from those that 'reside within' a population (endemic).
[3]
The term
'epidemiology' appears to have first been used to describe the study of epidemics in 1802 by the Spanish physician
Villalba in Epidemiología Española.
[3]
Epidemiologists also study the interaction of diseases in a population, a
condition known as a syndemic.
The term epidemiology is now widely applied to cover the description and causation of not only epidemic disease,
but of disease in general, and even many non-disease health-related conditions, such as high blood pressure and
obesity.
History
The Greek physician Hippocrates has been called the father of epidemiology.
[4]
He is the first person known to have
examined the relationships between the occurrence of disease and environmental influences.
[5]
He coined the terms
endemic (for diseases usually found in some places but not in others) and epidemic (for disease that are seen at some
times but not others).
[6]
Epidemiology is defined as the study of distribution and determinants of health related states in populations and use
of this study to address health related problems. One of the earliest theories on the origin of disease was that it was
primarily the fault of human luxury. This was expressed by philosophers such as Plato
[7]
and Rousseau,
[8]
and social
critics like Jonathan Swift.
[9]
In the middle of the 16th century, a doctor from Verona named Girolamo Fracastoro was the first to propose a theory
that these very small, unseeable, particles that cause disease were alive. They were considered to be able to spread by
air, multiply by themselves and to be destroyable by fire. In this way he refuted Galen's miasma theory (poison gas
in sick people). In 1543 he wrote a book De contagione et contagiosis morbis, in which he was the first to promote
personal and environmental hygiene to prevent disease. The development of a sufficiently powerful microscope by
Anton van Leeuwenhoek in 1675 provided visual evidence of living particles consistent with a germ theory of
disease.

Epidemiology 21
Original map by John Snow showing the clusters of cholera cases in the London
epidemic of 1854
John Graunt, a professional haberdasher and
serious amateur scientist, published Natural
and Political Observations ... upon the Bills
of Mortality in 1662. In it, he used analysis
of the mortality rolls in London before the
Great Plague to present one of the first life
tables and report time trends for many
diseases, new and old. He provided
statistical evidence for many theories on
disease, and also refuted many widespread
ideas on them.
Dr. John Snow is famous for his
investigations into the causes of the 19th
century cholera epidemics. He began with
noticing the significantly higher death rates
in two areas supplied by Southwark
Company. His identification of the Broad
Street pump as the cause of the Soho
epidemic is considered the classic example
of epidemiology. He used chlorine in an
attempt to clean the water and had the
handle removed, thus ending the outbreak. This has been perceived as a major event in the history of public health
and can be regarded as the founding event of the science of epidemiology.
Other pioneers include Danish physician Peter Anton Schleisner, who in 1849 related his work on the prevention of
the epidemic of neonatal tetanus on the Vestmanna Islands in Iceland.
[10] [11]
Another important pioneer was
Hungarian physician Ignaz Semmelweis, who in 1847 brought down infant mortality at a Vienna hospital by
instituting a disinfection procedure. His findings were published in 1850, but his work was ill received by his
colleagues, who discontinued the procedure. Disinfection did not become widely practiced until British surgeon
Joseph Lister 'discovered' antiseptics in 1865 in light of the work of Louis Pasteur.
In the early 20th century, mathematical methods were introduced into epidemiology by Ronald Ross, Anderson Gray
McKendrick and others.
Another breakthrough was the 1954 publication of the results of a British Doctors Study, led by Richard Doll and
Austin Bradford Hill, which lent very strong statistical support to the suspicion that tobacco smoking was linked to
lung cancer.
• History of emerging infectious diseases
The profession
To date, few universities offer epidemiology as a course of study at the undergraduate level. Many epidemiologists
are physicians, or hold graduate degrees such as a Master of Public Health (MPH), Master of Science or
Epidemiology (MSc.). Doctorates include the Doctor of Public Health (DrPH), Doctor of Pharmacy (PharmD),
Doctor of Philosophy (PhD), Doctor of Science (ScD), or for clinically trained physicians, Doctor of Medicine (MD)
and Doctor of Veterinary Medicine (DVM) . In the United Kingdom, the title of 'doctor' is by long custom used to
refer to general medical practitioners, whose professional degrees are usually those of Bachelor of Medicine and
Surgery (MBBS or MBChB). As public health/health protection practitioners, epidemiologists work in a number of
different settings. Some epidemiologists work 'in the field'; i.e., in the community, commonly in a public

Epidemiology 22
health/health protection service and are often at the forefront of investigating and combating disease outbreaks.
Others work for non-profit organizations, universities, hospitals and larger government entities such as the Centers
for Disease Control and Prevention (CDC), the Health Protection Agency, The World Health Organization (WHO),
or the Public Health Agency of Canada. Epidemiologists can also work in for-profit organizations such as
pharmaceutical and medical device companies in groups such as market research or clinical development.
The practice
Epidemiologists employ a range of study designs from the observational to experimental and generally categorized
as descriptive, analytic (aiming to further examine known associations or hypothesized relationships), and
experimental (a term often equated with clinical or community trials of treatments and other interventions).
Epidemiological studies are aimed, where possible, at revealing unbiased relationships between exposures such as
alcohol or smoking, biological agents, stress, or chemicals to mortality or morbidity. The identification of causal
relationships between these exposures and outcomes is an important aspect of epidemiology. Modern
epidemiologists use informatics as a tool.
The term 'epidemiologic triad' is used to describe the intersection of Host, Agent, and Environment in analyzing an
outbreak.
As causal inference
Although epidemiology is sometimes viewed as a collection of statistical tools used to elucidate the associations of
exposures to health outcomes, a deeper understanding of this science is that of discovering causal relationships.
It is nearly impossible to say with perfect accuracy how even the most simple physical systems behave beyond the
immediate future, much less the complex field of epidemiology, which draws on biology, sociology, mathematics,
statistics, anthropology, psychology, and policy; "Correlation does not imply causation" is a common theme for
much of the epidemiological literature. For epidemiologists, the key is in the term inference. Epidemiologists use
gathered data and a broad range of biomedical and psychosocial theories in an iterative way to generate or expand
theory, to test hypotheses, and to make educated, informed assertions about which relationships are causal, and about
exactly how they are causal. Epidemiologists Rothman and Greenland emphasize that the "one cause - one effect"
understanding is a simplistic mis-belief. Most outcomes, whether disease or death, are caused by a chain or web
consisting of many component causes. Causes can be distinguished as necessary, sufficient or probabilistic
conditions. If a necessary condition can be identified and controlled (e.g., antibodies to a disease agent), the harmful
outcome can be avoided.
Bradford-Hill criteria
In 1965 Austin Bradford Hill detailed criteria for assessing evidence of causation.
[12]
These guidelines are
sometimes referred to as the Bradford-Hill criteria, but this makes it seem like it is some sort of checklist. For
example, Phillips and Goodman (2004) note that they are often taught or referenced as a checklist for assessing
causality, despite this not being Hill's intention.
[13]
Hill himself said "None of my nine viewpoints can bring
indisputable evidence for or against the cause-and-effect hypothesis and none can be required sine qua non".
[12]
1. Strength: A small association does not mean that there is not a causal effect, though the larger the association,
the more likely that it is causal.
[12]
2. Consistency: Consistent findings observed by different persons in different places with different samples
strengthens the likelihood of an effect.
[12]
3. Specificity: Causation is likely if a very specific population at a specific site and disease with no other likely
explanation. The more specific an association between a factor and an effect is, the bigger the probability of a
causal relationship.
[12]

Epidemiology 23
4. Temporality: The effect has to occur after the cause (and if there is an expected delay between the cause and
expected effect, then the effect must occur after that delay).
[12]
5. Biological gradient: Greater exposure should generally lead to greater incidence of the effect. However, in some
cases, the mere presence of the factor can trigger the effect. In other cases, an inverse proportion is observed:
greater exposure leads to lower incidence.[12]
6. Plausibility: A plausible mechanism between cause and effect is helpful (but Hill noted that knowledge of the
mechanism is limited by current knowledge).
[12]
7. Coherence: Coherence between epidemiological and laboratory findings increases the likelihood of an effect.
However, Hill noted that "... lack of such [laboratory] evidence cannot nullify the epidemiological effect on
associations".
[12]
8. Experiment: "Occasionally it is possible to appeal to experimental evidence".
[12]
9. Analogy: The effect of similar factors may be considered.
[12]
Legal interpretation
Epidemiological studies can only go to prove that an agent could have caused, but not that it did cause, an effect in
any particular case:
"Epidemiology is concerned with the incidence of disease in populations and does not address the
question of the cause of an individual's disease. This question, sometimes referred to as specific
causation, is beyond the domain of the science of epidemiology. Epidemiology has its limits at the point
where an inference is made that the relationship between an agent and a disease is causal (general
causation) and where the magnitude of excess risk attributed to the agent has been determined; that is,
epidemiology addresses whether an agent can cause a disease, not whether an agent did cause a specific
plaintiff's disease."
[14]
In United States law, epidemiology alone cannot prove that a causal association does not exist in general.
Conversely, it can be (and is in some circumstances) taken by US courts, in an individual case, to justify an inference
that a causal association does exist, based upon a balance of probability.
The subdiscipline of forensic epidemiology is directed at the investigation of specific causation of disease or injury
in individuals or groups of individuals in instances in which causation is disputed or is unclear, for presentation in
legal settings.
Advocacy
As a public health discipline, epidemiologic evidence is often used to advocate both personal measures like diet
change and corporate measures like removal of junk food advertising, with study findings disseminated to the
general public to help people to make informed decisions about their health. Often the uncertainties about these
findings are not communicated well; news articles often prominently report the latest result of one study with little
mention of its limitations, caveats, or context. Epidemiological tools have proved effective in establishing major
causes of diseases like cholera and lung cancer,
[12]
but experience difficulty in regards to more subtle health issues
where causation is not as clear. Notably, conclusions drawn from observational studies may be reconsidered as later
data from randomized controlled trials becomes available, as was the case with the association between the use of
hormone replacement therapy and cardiac risk.
[15]

Epidemiology 24
Population-based health management
Epidemiological practice and the results of epidemiological analysis make a significant contribution to emerging
population-based health management frameworks.
Population-based health management encompasses the ability to:
• Assess the health states and health needs of a target population;
• Implement and evaluate interventions that are designed to improve the health of that population; and
• Efficiently and effectively provide care for members of that population in a way that is consistent with the
community's cultural, policy and health resource values.
Modern population-based health management is complex, requiring a multiple set of skills (medical, political,
technological, mathematical etc.) of which epidemiological practice and analysis is a core component, that is unified
with management science to provide efficient and effective health care and health guidance to a population. This task
requires the forward looking ability of modern risk management approaches that transform health risk factors,
incidence, prevalence and mortality statistics (derived from epidemiological analysis) into management metrics that
not only guide how a health system responds to current population health issues, but also how a health system can be
managed to better respond to future potential population health issues.
Examples of organizations that use population-based health management that leverage the work and results of
epidemiological practice include Canadian Strategy for Cancer Control, Health Canada Tobacco Control Programs,
Rick Hansen Foundation, Canadian Tobacco Control Research Initiative.
[16] [17] [18]
Each of these organizations use a population-based health management framework called Life at Risk that combines
epidemiological quantitative analysis with demographics, health agency operational research and economics to
perform:
• Population Life Impacts Simulations: Measurement of the future potential impact of disease upon the population
with respect to new disease cases, prevalence, premature death as well as potential years of life lost from
disability and death;
• Labour Force Life Impacts Simulations: Measurement of the future potential impact of disease upon the labour
force with respect to new disease cases, prevalence, premature death and potential years of life lost from disability
and death;
• Economic Impacts of Disease Simulations: Measurement of the future potential impact of disease upon private
sector disposable income impacts (wages, corporate profits, private health care costs) and public sector disposable
income impacts (personal income tax, corporate income tax, consumption taxes, publicly funded health care
costs).
Types of studies
Case series
Case-series may refer to the qualititative study of the experience of a single patient, or small group of patients with a
similar diagnosis, or to a statistical technique comparing periods during which patients are exposed to some factor
with the potential to produce illness with periods when they are unexposed.
The former type of study is purely descriptive and cannot be used to make inferences about the general population of
patients with that disease. These types of studies, in which an astute clinician identifies an unusual feature of a
disease or a patient's history, may lead to formulation of a new hypothesis. Using the data from the series, analytic
studies could be done to investigate possible causal factors. These can include case control studies or prospective
studies. A case control study would involve matching comparable controls without the disease to the cases in the
series. A prospective study would involve following the case series over time to evaluate the disease's natural
history.
[19]

Epidemiology 25
The latter type, more formally described as self-controlled case-series studies, divide individual patient follow-up
time into exposed and unexposed periods and use fixed-effects Poisson regression processes to compare the
incidence rate of a given outcome between exposed and unexposed periods. This technique has been extensively
used in the study of adverse reactions to vaccination, and has been shown in some circumstances to provide
statistical power comparable to that available in cohort studies.
Case control studies
Case control studies select subjects based on their disease status. A group of individuals that are disease positive (the
"case" group) is compared with a group of disease negative individuals (the "control" group). The control group
should ideally come from the same population that gave rise to the cases. The case control study looks back through
time at potential exposures that both groups (cases and controls) may have encountered. A 2x2 table is constructed,
displaying exposed cases (A), exposed controls (B), unexposed cases (C) and unexposed controls (D). The statistic
generated to measure association is the odds ratio (OR), which is the ratio of the odds of exposure in the cases (A/C)
to the odds of exposure in the controls (B/D), i.e. OR = (A/C) / (B/D) .
..... Cases Controls
Exposed A B
Unexposed C D
If the OR is clearly greater than 1, then the conclusion is "those with the disease are more likely to have been
exposed," whereas if it is close to 1 then the exposure and disease are not likely associated. If the OR is far less than
one, then this suggests that the exposure is a protective factor in the causation of the disease.
Case control studies are usually faster and more cost effective than cohort studies, but are sensitive to bias (such as
recall bias and selection bias). The main challenge is to identify the appropriate control group; the distribution of
exposure among the control group should be representative of the distribution in the population that gave rise to the
cases. This can be achieved by drawing a random sample from the original population at risk. This has as a
consequence that the control group can contain people with the disease under study when the disease has a high
attack rate in a population.
Cohort studies
Cohort studies select subjects based on their exposure status. The study subjects should be at risk of the outcome
under investigation at the beginning of the cohort study; this usually means that they should be disease free when the
cohort study starts. The cohort is followed through time to assess their later outcome status. An example of a cohort
study would be the investigation of a cohort of smokers and non-smokers over time to estimate the incidence of lung
cancer. The same 2x2 table is constructed as with the case control study. However, the point estimate generated is
the Relative Risk (RR), which is the probability of disease for a person in the exposed group, P
e
= A / (A+B) over
the probability of disease for a person in the unexposed group, P
u
= C / (C+D), i.e. RR = P
e
/ P
u
.

Epidemiology 26
..... Case Non case Total
Exposed A B (A+B)
Unexposed C D (C+D)
As with the OR, a RR greater than 1 shows association, where the conclusion can be read "those with the exposure
were more likely to develop disease."
Prospective studies have many benefits over case control studies. The RR is a more powerful effect measure than the
OR, as the OR is just an estimation of the RR, since true incidence cannot be calculated in a case control study where
subjects are selected based on disease status. Temporality can be established in a prospective study, and confounders
are more easily controlled for. However, they are more costly, and there is a greater chance of losing subjects to
follow-up based on the long time period over which the cohort is followed.
Outbreak investigation
For information on investigation of infectious disease outbreaks, please see outbreak investigation.
Validity: precision and bias
Random error
Random error is the result of fluctuations around a true value because of sampling variability. Random error is just
that: random. It can occur during data collection, coding, transfer, or analysis. Examples of random error include:
poorly worded questions, a misunderstanding in interpreting an individual answer from a particular respondent, or a
typographical error during coding. Random error affects measurement in a transient, inconsistent manner and it is
impossible to correct for random error.
There is random error in all sampling procedures. This is called sampling error.
Precision in epidemiological variables is a measure of random error. Precision is also inversely related to random
error, so that to reduce random error is to increase precision. Confidence intervals are computed to demonstrate the
precision of relative risk estimates. The narrower the confidence interval, the more precise the relative risk estimate.
There are two basic ways to reduce random error in an epidemiological study. The first is to increase the sample size
of the study. In other words, add more subjects to your study. The second is to reduce the variability in measurement
in the study. This might be accomplished by using a more precise measuring device or by increasing the number of
measurements.
Note, that if sample size or number of measurements are increased, or a more precise measuring tool is purchased,
the costs of the study are usually increased. There is usually an uneasy balance between the need for adequate
precision and the practical issue of study cost.
Systematic error
A systematic error or bias occurs when there is a difference between the true value (in the population) and the
observed value (in the study) from any cause other than sampling variability. An example of systematic error is if,
unbeknown to you, the pulse oximeter you are using is set incorrectly and adds two points to the true value each time
a measurement is taken. The measuring device could be precise but not accurate. Because the error happens in every
instance, it is systematic. Conclusions you draw based on that data will still be incorrect. But the error can be
reproduced in the future (e.g., by using the same mis-set instrument).
A mistake in coding that affects all responses for that particular question is another example of a systematic error.

Epidemiology 27
The validity of a study is dependent on the degree of systematic error. Validity is usually separated into two
components:
• Internal validity is dependent on the amount of error in measurements, including exposure, disease, and the
associations between these variables. Good internal validity implies a lack of error in measurement and suggests
that inferences may be drawn at least as they pertain to the subjects under study.
• External validity pertains to the process of generalizing the findings of the study to the population from which the
sample was drawn (or even beyond that population to a more universal statement). This requires an understanding
of which conditions are relevant (or irrelevant) to the generalization. Internal validity is clearly a prerequisite for
external validity.
Three types of bias
Selection bias
Selection bias is one of three types of bias that can threaten the validity of a study. Selection bias occurs when study
subjects are selected or become part of the study as a result of a third, unmeasured variable which is associated with
both the exposure and outcome of interest.
[20]
Examples of selection bias are volunteer bias (the opposite of which is non-response bias)
[21]
in which participants
and non participants differ in terms of exposure and outcome. For instance, it has repeatedly been noted that cigarette
smokers and non smokers tend to differ in their study participation rates. (Sackett D cites the example of Seltzer et
al., in which 85% of non smokers and 67% of smokers returned mailed questionnaires)[21]
It is important to note that
such a difference in response will not lead to bias if it is not also associated with a systematic difference in outcome
between the two response groups.
Confounding
Confounding has traditionally been defined as bias arising from the co-occurrence or mixing of effects of extraneous
factors, referred to as confounders, with the main effect(s) of interest.
[22] [23]
A more recent definition of
confounding invokes the notion of counterfactual effects.
[23]
According to this view, when one observes an outcome
of interest, say Y=1 (as opposed to Y=0), in a given population A which is entirely exposed (i.e. exposure X=1 for
every unit of the population) the risk of this event will be R
A1
. The counterfactual or unobserved risk R
A0
corresponds to the risk which would have been observed if these same individuals had been unexposed (i.e. X=0 for
every unit of the population). The true effect of exposure therefore is: R
A1
- R
A0
(if one is interested in risk
differences) or R
A1
/R
A0
(if one is interested in relative risk). Since the counterfactual risk R
A0
is unobservable we
approximate it using a second population B and we actually measure the following relations: R
A1
- R
B0
or R
A1
/R
B0
.
In this situation, confounding occurs when R
A0
≠ R
B0
.
[23]
(NB: Example assumes binary outcome and exposure variables.)
Information bias
Information bias is bias arising from systematic error in the assessment of a variable.
[22]
An example of this is recall
bias. A typical example is again provided by Sackett in his discussion of a study examining the effect of specific
exposures on fetal health: "in questioning mothers whose recent pregnancies had ended in fetal death or
malformation (cases) and a matched group of mothers whose pregnancies ended normally (controls) it was found
that 28%; of the former, but only 20%,; of the latter, reported exposure to drugs which could not be substantiated
either in earlier prospective interviews or in other health records".
[21]
In this example, recall bias probably occurred
as a result of women who had had miscarriages having an apparent tendency to better recall and therefore report
previous exposures.

Epidemiology 28
Journals
A list of journals:
[24]
General journals:
• American Journal of Epidemiology
• Canadian Journal of Epidemiology and Biostatistics
[25]
• Epidemiologic Reviews
[26]
• Epidemiology
• International Journal of Epidemiology
• Annals of Epidemiology
• Journal of Epidemiology and Community Health
[27]
• European Journal of Epidemiology
• Emerging themes in epidemiology
• Epidemiologic Perspectives and Innovations
[28]
• Eurosurveillance
[29]
Specialty journals:
• Cancer Epidemiology Biomarkers and Prevention
[30]
• Genetic epidemiology
• Journal of Clinical Epidemiology
• Epidemiology and Infection
• Paediatric Perinatal Epidemiology
[31]
• Pharmacoepidemiology and Drug Safety
[32]
• Preventive Medicine
[33]
Areas
By physiology/disease:
• Infectious disease epidemiology
• Occupational Injury & Illness epidemiology
• Cardiovascular disease epidemiology
• Cancer epidemiology
• Neuroepidemiology
• Epidemiology of Aging
• Oral/Dental epidemiology
• Reproductive epidemiology
• Obesity/diabetes epidemiology
• Renal epidemiology
• Intestinal epidemiology
• Psychiatric epidemiology
• Veterinary epidemiology
• Epidemiology of zoonosis
• Respiratory Epidemiology
• Pediatric Epidemiology
• Quantitative parasitology
By methodological approach:
• Environmental epidemiology
• Economic epidemiology
• Clinical epidemiology
• Conflict epidemiology
• Cognitive epidemiology
• Genetic epidemiology
• Molecular epidemiology
• Nutritional epidemiology
• Social epidemiology
• Lifecourse epidemiology
• Epi methods development / Biostatistics
• Meta-analysis
• Spatial epidemiology
• Tele-epidemiology
• Biomarker epidemiology
• Pharmacoepidemiology
• Primary care epidemiology
• Infection control and hospital epidemiology
• Public Health practice epidemiology
• Surveillance epidemiology (Clinical surveillance)
• Disease Informatics

Epidemiology 29
References
Notes
[1] Nutter, Jr., F.W. (1999). "Understanding the interrelationships between botanical, human, and veterinary epidemiology: the Ys and Rs of it
all". Ecosys Health 5 (3): 131–40. doi:10.1046/j.1526-0992.1999.09922.x.
[2] Hippocrates. (~200BC). Airs, Waters, Places.
[3] Carol Buck, Alvaro Llopis, Enrique Nájera, Milton Terris. (1998). The Challenge of Epidemiology: Issues and Selected Readings. Scientific
Publication No. 505. Pan American Health Organization. Washington, DC. p3.
[4] Alfredo Morabia (2004). A history of epidemiologic methods and concepts (http://books.google.com/books?id=E-OZbEmPSTkC&
pg=PA93&dq&hl=en#v=onepage&q=&f=false). Birkhäuser. p. 93. ISBN 3764368187. .
[5] Ray M. Merrill (2010). Introduction to Epidemiology (http://books.google.com/books?id=RMDBh6gw1_UC&pg=PA24&dq&
hl=en#v=onepage&q=&f=false). Jones & Bartlett Learning. p. 24. ISBN 0763766224. .
[6] "Changing Concepts: Background to Epidemiology" (http://www.duncan-associates.com/changing_concepts.pdf). Duncan & Associates. .
Retrieved 2008-02-03.
[7] Plato. "The Republic" (http://classics.mit.edu/Plato/republic.4.iii.html). The Internet Classic Archive. . Retrieved 2008-02-03.
[8] "A Dissertation on the Origin and Foundation of the Inequality of Mankind" (http://www.constitution.org/jjr/ineq_03.htm). Constitution
Society. .
[9] Swift, Jonathan. "Gulliver's Travels: Part IV. A Voyage to the Country of the Houyhnhnms" (http://www.jaffebros.com/lee/gulliver/bk4/
chap4-7.html). . Retrieved 2008-02-03.
[10] Ólöf Garðarsdóttir; Loftur Guttormsson (June 2008). "An isolated case of early medical intervention. The battle against neonatal tetanus in
the island of Vestmannaeyjar (Iceland) during the 19th century" (http://ftp.ieg.csic.es/workshop/pdf/olofpaper.pdf). Instituto de
Economía y Geografía. . Retrieved 2011-04-19.
[11] Ólöf Garðarsdóttir; Loftur Guttormsson (25 August 2009). "Public health measures against neonatal tetanus on the island of Vestmannaeyjar
(Iceland) during the 19th century". The History of the Family 14 (3): 266–79. doi:10.1016/j.hisfam.2009.08.004.
[12] Hill, Austin Bradford (1965). "The environment and disease: association or causation?" (http://www.edwardtufte.com/tufte/hill).
Proceedings of the Royal Society of Medicine 58: 295–300. PMC 1898525. PMID 14283879. .
[13] Phillips, Carl V.; Karen J. Goodman (October 2004). "The missed lessons of Sir Austin Bradford Hill" (http://www.epi-perspectives.com/
content/1/1/3). Epidemiologic Perspectives and Innovations 1 (3): 3. doi:10.1186/1742-5573-1-3. PMC 524370. PMID 15507128. .
[14] Green, Michael D.; D. Michal Freedman, and Leon Gordis (PDF). Reference Guide on Epidemiology (http://www.fjc.gov/public/pdf.
nsf/lookup/sciman06.pdf/$file/sciman06.pdf). Federal Judicial Centre. . Retrieved 2008-02-03.
[15] Gabriel Sanchez R, Sanchez Gomez LM, Carmona L, Roqué i Figuls M, Bonfill Cosp X. Hormone replacement therapy for preventing
cardiovascular disease in post-menopausal women. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD002229. DOI:
10.1002/14651858.CD002229.pub2
[16] Smetanin, P.; P. Kobak (October 2005). "Interdisciplinary Cancer Risk Management: Canadian Life and Economic Impacts". 1st
International Cancer Control Congress (http://www.cancercontrol2005.com).
[17] Smetanin, P.; P. Kobak (July 2006). "A Population-Based Risk Management Framework for Cancer Control" (http://www.riskanalytica.
com/Library/Papers/Population Based Risk Management Framework for Cancer Control.pdf) (PDF). The International Union Against
Cancer Conference (http://www.2006conferences.org/u-index.php). .
[18] Smetanin, P.; P. Kobak (July 2005). "Selected Canadian Life and Economic Forecast Impacts of Lung Cancer" (http://www.riskanalytica.
com/Library/Papers/Canadian Lung Cancer Abstract Jan 2005.pdf) (PDF). 11th World Conference on Lung Cancer. .
[19] Hennekens, Charles H.; Julie E. Buring (1987). Mayrent, Sherry L. (Ed.). ed. Epidemiology in Medicine. Lippincott, Williams and Wilkins.
ISBN 978-0316356367.
[20] (http://journals.lww.com/epidem/Fulltext/2004/09000/A_Structural_Approach_to_Selection_Bias.20.aspx) 23
[21] (http://www.epidemiology.ch/history/PDF bg/Sackett DL 1979 bias in analytic research.pdf) 24
[22] Special:BookSources/0195135547 21
[23] (http://www.annualreviews.org/doi/full/10.1146/annurev.publhealth.22.1.189) 22
[24] "Epidemiologic Inquiry: Impact Factors of leading epidemiology journals" (http://www.epidemiologic.org/2006/10/
impact-factors-of-epidemiology-and.html). Epidemiologic.org. . Retrieved 2008-02-03.
[25] http://www.cjeb.ca/
[26] http://epirev.oxfordjournals.org
[27] http://jech.bmj.com
[28] http://www.epi-perspectives.com
[29] http://www.eurosurveillance.org
[30] http://cebp.aacrjournals.org
[31] http://www.blackwellpublishing.com/journal.asp?ref=0269-5022
[32] http://eu.wiley.com/WileyCDA/WileyTitle/productCd-PDS.html
[33] http://www.elsevier.com/wps/find/journaldescription.cws_home/622934/description#description

Epidemiology 30
Bibliography
• Clayton, David and Michael Hills (1993) Statistical Models in Epidemiology Oxford University Press. ISBN
0-19-852221-5
• Last JM (2001). "A dictionary of epidemiology", 4th edn, Oxford: Oxford University Press. 5th. edn (2008),
edited by Miquel Porta (http://www.oup.com/us/catalog/general/subject/Medicine/
EpidemiologyBiostatistics/?view=usa&ci=9780195314502)
• Morabia, Alfredo. ed. (2004) A History of Epidemiologic Methods and Concepts. Basel, Birkhauser Verlag. Part
I. (http://books.google.es/books?id=Hgnnhu1ym-8C&dq=Morabia,+Alfredo.+ed.+(2004)+A+History+
of+Epidemiologic+Methods&printsec=frontcover&source=bn&hl=es&ei=U4ARSvbaEJGUjAew8LnCBg&
sa=X&oi=book_result&ct=result&resnum=4) (http://www.springer.com/public+health/book/
978-3-7643-6818-0)
• Smetanin P., Kobak P., Moyer C., Maley O (2005) "The Risk Management of Tobacco Control Research Policy
Programs" The World Conference on Tobacco OR Health Conference, July 12–15, 2006 in Washington DC.
• Szklo MM & Nieto FJ (2002). "Epidemiology: beyond the basics", Aspen Publishers, Inc.
• Rothman, Kenneth, Sander Greenland and Timothy Lash (2008). "Modern Epidemiology", 3rd Edition,
Lippincott Williams & Wilkins. ISBN 0781755646, ISBN 978-0781755641
• Rothman, Kenneth (2002). "Epidemiology. An introduction", Oxford University Press. ISBN 0195135547, ISBN
978-0195135541
External links
• The Health Protection Agency (http://www.hpa.org.uk)
• The Collection of Biostatistics Research Archive (http://www.biostatsresearch.com/repository/)
• Statistical Applications in Genetics and Molecular Biology (http://www.bepress.com/sagmb/)
• The International Journal of Biostatistics (http://www.bepress.com/ijb/)
• European Epidemiological Federation (http://www.iea-europe.org/index.htm)
• BMJ (http://bmj.bmjjournals.com/epidem/epid.html) - Epidemiology for the Uninitiated' (fourth edition), D.
Coggon, G. Rose, D.J.P. Barker British Medical Journal
• Epidem.com (http://www.epidem.com) - Epidemiology (peer reviewed scientific journal that publishes original
research on epidemiologic topics)
• NIH.gov (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.chapter.631) - 'Epidemiology' (textbook
chapter), Philip S. Brachman, Medical Microbiology (fourth edition), US National Center for Biotechnology
Information
• UTMB.edu (http://gsbs.utmb.edu/microbook/) - 'Epidemiology' (plain format chapter), Philip S. Brachman,
Medical Microbiology
• Monash Virtual Laboratory (http://vlab.infotech.monash.edu.au/simulations/cellular-automata/epidemic/) -
Simulations of epidemic spread across a landscape
• EMER (http://sist-emer.net/?lang=en)- Epizootic Diseases, Emerging and Re-emerging Diseases
• Umeå Centre for Global Health Research
• Epidemiology and Public Health Sciences, Umeå International School of Public Health (http://www8.umu.se/
phmed/epidemi/index.html/)
• Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (http://
dceg.cancer.gov/)
• The Centre for Research on the Epidemiology of Disasters (CRED) at the Université catholique de Louvain
(UCL) (http://www.cred.be)
• People's Epidemiology Library (http://www.epidemiology.ch/history/betaversion.htm)

Subjects and Topics in Basic Medical Science-A Imhotep Virtual Medical School Primer

Subjects and Topics in Basic Medical Science-A Imhotep Virtual Medical School Primer

Recommended

Recommended

More Related Content

What's hot

What's hot (19)

Viewers also liked

Viewers also liked (20)

Similar to Subjects and Topics in Basic Medical Science-A Imhotep Virtual Medical School Primer

Similar to Subjects and Topics in Basic Medical Science-A Imhotep Virtual Medical School Primer (20)

More from Imhotep Virtual Medical School

More from Imhotep Virtual Medical School (20)

Recently uploaded

Recently uploaded (20)

Subjects and Topics in Basic Medical Science-A Imhotep Virtual Medical School Primer