Menselijke biologie en ziekteleer

1. Chemistry of Life (hoofdstuk 2 handboek)

1.1 From atoms to molecules (NIET KENNEN EXAMEN)
• Important terms
o Matter is anything that takes up space and has mass. It can exist as a solid (vast), gas,
liquid (vloeibaar), or plasma.
▪ Examples: humans are composed of matter, but so if food, water, air, …
o An element is one of the basic building blocks of matter; it cannot be broken down
by chemical means.
▪ Over 90% of the human body is composed of just four elements: carbon
(koolstof), nitrogen (stikstof), oxygen (zuurstof), and hydrogen (waterstof).
▪ Even so, other elements, such as iron (ijzer), are important to our health.
o An atom is the smallest unit of an element that still retains (behouden) the chemical
and physical properties of the element. The same name is given to the element and
the atoms of the element. It is possible to split an atom.
They bond together to form a molecule (zie verder).
▪ The three best known subatomic particles are
positively charged protons, uncharged
neutrons, and negatively charged electrons.
Protons and neutrons are located within the
nucleus of an atom, and electrons move about
the nucleus (kern).
▪ The circle around the nucleus of the atom
represents an electron shell, which represents
the average location of electrons.
▪ All atoms of an element have the same number of protons housed in the
nucleus. This is called the atomic number, which accounts for the unique
properties of this type of atom.
▪ Each atom also has its own mass number,
dependent on the number of subatomic
particles in that atom. The mass number is the sum of the protons and
neurons in the nucleus.
▪ The atomic mass (the number below the atomic symbol on the periodic
table) is the average of the AMU (atomic mass unit) for all the isotopes
(discussed next) of that atom.
o Isotopes of the same type of atom have the same number of protons but different
numbers of neutrons. Therefore, they have the same atomic number but their mass
numbers are different.
▪ Radioisotopes release various types of energy in the form of rays and
subatomic particles. This is because they are unstable. The radiation given
off by radioisotopes can be detected in various ways.
- Low levels of radiation are useful in dating old objects, imaging body
organs and tissues (weefsel) through X-rays, can be used to diagnose
the presence of turmors, and can be used as PET scans.
- High levels of radiations can harm cells, damage DNA, and cause
cancer, however they can also be put to good use for sterilizing food

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 by killing bacteria and fungi, which increases the shelf life of the food
and physicians can use radiation therapy to kill cancer cells.
o Atoms often bond with one another to form a chemical unit called a molecule. They
can contain atoms of the same type (O2) or atoms of different types (H²O). When the
atoms are different, a compound is formed.
▪ Two types of bonds join atoms: ionic bonds and covalent bonds.
- Atoms with more than one shell are most stable when the outer
shell, also called the valence shell, contains eight electrons. During
an ionic reaction, atoms give up or take on an electron or electrons
to achieve a stable valence shell.
- Ions are particles that carry either a positive (+) or a negative (−)
charge. The attraction between oppositely charged ions form an
ionic bond.
❖ For example: table salt (sodium chloride)
❖ The balance of various ions in the body is important to our
health. Too much sodium in the blood can contribute to high
blood pressure, for example.
❖ Ionic bonds can be dissolved (in water for example), so those
bonds are a bit weaker.
- Atoms share electrons in covalent bonds. The overlapping,
outermost shells indicate that the atoms are sharing electrons.
❖ In a double bond, atoms share two pairs of electrons
❖ In a triple bond, atoms share three pairs of electrons
➢ Those bonds are stronger.
➢ Structural and molecular formulas
» Structural formulas use straight lines to
show the covalent bonds between the
atoms.
» Molecular formulas indicate only the
number of each type of atom making up a
molecule.

1.2 Water and life

• Water
o Water is the most abundant (overvloedige) molecule in living organisms, usually
making up about 60–70% of the total body weight. Furthermore, the physical and
chemical properties (eigenschappen) of water make life as we know it possible.
o Water is a polar molecule: the oxygen end of the molecule has a slight negative
charge (δ−), and the hydrogen end has a slight positive charge (δ+).

• Hydrogen bonds
o A hydrogen bond is the attraction of a slightly positive, covalently bonded hydrogen
to a slightly negative atom in the vicinity.
▪ These usually occur between a hydrogen and either an oxygen or a nitrogen
atom.
▪ A hydrogen bond is represented by a dotted line because it is relatively weak
and can be broken rather easily.

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• Properties (eigenschappen) of water
o Because of hydrogen bonding, water molecules cling together, and this association
gives water its unique chemical properties.
▪ Without hydrogen bonding between molecules, water would freeze at
−100°C and boil at −91°C, making most of the water on earth steam and life
unlikely.
▪ Hydrogen bonding is responsible for water being a liquid at temperatures
typically found on the earth’s surface (room temperatures). It freezes at 0°C
and boils at 100°C. These and other unique properties of water make it
essential to the existence of life as we know it.
o Water has a high heat capacity
▪ Water holds on to its heat, and its temperature falls more slowly than that of
other liquids. Because the temperature of water rises and falls slowly, we are
better able to maintain our normal internal temperature and are protected
from rapid temperature changes → thermal stability.
o Water has a high heat of evaporation
▪ Water’s high heat of vaporization gives our bodies an efficient way to release
excess body heat in a hot environment. When we sweat, or get splashed
with water, body heat is used to vaporize the water, thus cooling us down.
o Water is solvent (oplosmiddel)
▪ Due to its polarity, water facilitates chemical reactions, both outside and
within living systems. As a solvent, it dissolves a great number of substances,
especially those that, like water, are polar. A solution (een oplossing)
contains dissolved substances, which are then called solutes.
- For example NaCl in water!
▪ Molecules that can attract water are said to be hydrophilic. When ions and
molecules disperse in water, they move about and collide, allowing reactions
to occur.
▪ Molecules that cannot attract water, also known as nonpolar molecules, are
said to be hydrophobic. Hydrophilic molecules tend to attract other polar
molecules; similarly, hydrophobic substances usually associate with other
nonpolar molecules.
o Water molecules are cohesive and adhesive.
▪ Cohesion refers to the ability of water molecules to cling to each other. This
is due to the hydrogen bonds between water molecules.
- Because of cohesion, water exists as a liquid under the conditions of
temperature and pressure present at the earth’s surface.
▪ Adhesion refers to the ability of water molecules to cling to a surface.
Because water is polar, it is attracted to other polar surfaces.
o Frozen water is less dense than liquid water
▪ As liquid water cools, the molecules come closer together. At temperatures
below 4°C, only vibrational movement occurs, and hydrogen bonding
becomes more rigid but also more open.
- This means that water expands as it reaches 0°C and freezes.
- It also means that ice is less dense than liquid water, and therefore
ice floats on liquid water.

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• Acids and bases
o When water molecules dissociate (break up), they release an equal number of
hydrogen ions (H+) and hydroxide ions (OH−). A mole is a unit of scientific
measurement for atoms, ions, and molecules.
o Acidic solutions (High H+ concentrations)
▪ Acids (zuren) are substances that dissociate in water, releasing hydrogen
ions (H+). The acidity (de zuurtegraad) of a substance depends on how fully
it dissociates in water.
o Basic solutions (low H+ concentrations)
▪ Bases are substances that either take up hydrogen ions (H+) or release
hydroxide ions (OH−).
o Some acids and bases are strong, meaning that they donate a large number of H+ or
OH− ions.
▪ You should not taste strong acids or bases, because they are destructive to
cells.
o Ph-scale
▪ The pH scale is used to indicate the acidity or basicity
(alkalinity) of a solution.
- The pH scale ranges from 0 to 14.
- A pH of 7 represents a neutral state in which
the hydrogen ion and hydroxide ion
concentrations are equal (pure water).
- A pH below 7 is an acidic solution, because the
hydrogen ion concentration is greater than the
hydroxide concentration.
- A pH above 7 is basic, because the [OH−] is
greater than the [H+].
▪ Further, as we move down the pH scale from pH 14 to pH 0, each unit is 10
times more acidic than the previous unit. As we move up the scale from 0 to
14, each unit is 10 times more basic than the previous unit.
▪ The pH scale was devised to eliminate the use of cumbersome numbers.
o Buffers
▪ Buffers help keep the pH within normal limits, because they are chemicals or
combinations of chemicals that take up excess hydrogen ions (H+) or
hydroxide ions (OH−).

1.3 Molecules of life

• Molecules
o Four categories of organic molecules—carbohydrates, lipids, proteins, and nucleic
acids—are unique to cells. In biology, “organic” refers to a molecule that contains
carbon (C) and hydrogen (H) and is usually associated with living organisms.
o Each type of organic molecule in cells is composed of subunits.
▪ When a cell constructs a macromolecule, a molecule that contains many
subunits, it uses a dehydration reaction, a type of synthesis reaction.
▪ To break down macromolecules, the cell uses a hydrolysis reaction in which
the components of water are added during the breaking of the bond
between the molecules.

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1.3.1 Carbohydrates
• Carbohydrates
o Carbohydrates are almost universally used as an energy source for living organisms,
including humans.
o Simple carbohydrates: monosaccharides
▪ Monosaccharides (mono = one; saccharide = sugar) consist of only a single
sugar molecule and are commonly called simple sugars. A monosaccharide
can have a carbon backbone of three to seven carbons.
- Most common = glucose (it’s a hexose, so 6 carbons)
- Other common hexoses are fructose (in fruits), galactose (in milk)
▪ Monosaccharides are the monomers that are used to build longer
carbohydrate chains.
o Disaccharides
▪ A disaccharide (di, “two”; saccharide, “sugar”) is made by joining only two
monosaccharides together by a dehydration reaction.
- Maltose, for example, is a disaccharide formed by a dehydration
reaction between two glucose molecules.
❖ When our hydrolytic digestive juices break down maltose,
the result is two glucose molecules.
- Sucrose = combination of fructose and glucose, is known as table
sugar!
- Lactose = combination of galactose and glucose
❖ People who are lactose intolerant cannot break down the
galactose.
o Complex carbohydrates: polysaccharides
▪ Long polymers such as starch, glycogen, and cellulose
are polysaccharides (poly, many) that contain long chains of glucose
subunits.
- Due to their length, they are sometimes referred to as complex
carbohydrates.
▪ Starch and glycogen have slightly different structures.
- Starch (zetmeel) has fewer side branches, or chains, than does
glycogen. Because starches are the storage form of carbohydrates in
plants, we typically find them in roots (such as potatoes) and in
seeds, such as wheat.
- Glycogen is an animal complex carbohydrate, it is the storage form
in animals. It is more branched than starch.
▪ The polysaccharide cellulose, commonly called fiber, is found in plant cell
walls. In cellulose, the glucose units are joined by a slightly different type of
linkage than that in starch or glycogen.
- It is also a plant complex carbohydrate.

1.3.2 Lipids
• Lipids
o Lipids are diverse in structure and function, but they have a common characteristic:
they do not dissolve in water.
▪ Their low solubility in water is due to an absence of hydrophilic polar groups.
They contain little oxygen and consist mostly of carbon and hydrogen atoms.

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o Lipids contain more energy per gram than other biological molecules; therefore, fats
in animals and oils in plants function well as energy storage molecules.
o Steroids are a large class of lipids that includes, among other molecules, the sex
hormones.
o Sorts of lipids
▪ Triglycerides: fats and oils
- The most familiar lipids are called the triglycerides. You may
commonly know these as fats and oils.
❖ Fats, usually of animal origin (e.g., lard and butter), are solid
at room temperature.
❖ Oils, usually of plant origin (e.g., corn oil and soybean oil),
are liquid at room temperature.
- The term triglyceride refers to the three-part structure of the
molecule. Triglycerides are formed when one glycerol molecule
reacts with three fatty acid molecules (vetzuur staarten) using a
dehydration synthesis reaction.
❖ A fatty acid is a carbon-hydrogen chain that ends with the
acidic group —COOH. Most of the fatty acids in cells contain
16 or 18 carbon atoms per molecule, although smaller ones
with fewer carbons are also known. Fatty acids are either
saturated or unsaturated.
➢ Saturated fatty acids have no double bonds
between the carbon atoms. The chain is saturated,
so to speak, with all the hydrogens it can hold.
➢ Unsaturated fatty acids have double bonds in the
carbon chain wherever the number of hydrogens is
less than two per carbon.
➢ Even more harmful than naturally occurring
saturated fats are the trans fats (trans in Latin
means “across”) that are created artificially from
vegetable oils. Their bonds are difficult to break,
allowing these trans fats to accumulate in the
circulatory system. Trans fats are found in
shortenings, solid margarines, and many processed
foods (snack foods, baked goods, and fried foods).
- Triglycerides have several functions in the body.
❖ They are used for long-term energy storage
❖ Insulate against heat loss
❖ Form a protective cushion around major organs
▪ Phospholipids
- Phospholipids have a phosphate group. They are constructed like
fats, except that in place of the third fatty acid, there is a phosphate
group or a grouping that contains both phosphate and nitrogen
(which are ionised).
- Phospholipids are the primary components of the plasma
membranes in cells. In a water environment, they spontaneously
form a bilayer (a sort of molecular “sandwich”) in which the
hydrophilic heads (the sandwich “bread”) face outward toward

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 watery solutions, and the tails (the sandwich “filling”) form the
hydrophobic interior.
▪ Steroids
- Steroids are lipids that have an entirely different structure from
those of fats. Steroid molecules have a backbone of four fused
carbon rings. Each one differs primarily in the functional
groups attached to the rings. One example of a steroid is cholesterol.
❖ Cholesterol is a component of an animal cell’s plasma
membrane and is the precursor of several other steroids,
such as the sex hormones oestrogen and testosterone. The
liver usually makes all the cholesterol the body needs.
➢ The male sex hormone testosterone is formed
primarily in the testes; the female sex hormone
oestrogen is formed primarily in the ovaries.
➢ Testosterone and oestrogen differ only by the
functional groups attached to the same carbon
backbone. However, they have a profound effect on
the body and the sexuality of humans and other
animals.
➢ The taking of anabolic steroids, usually to build
muscle strength, is illegal because the side effects
are harmful to the body

1.3.3 Proteins
• Proteins (eiwitten)
o Proteins are of primary importance in the structure and function of cells. Some of
their many functions in humans include:
▪ Support: Some proteins are structural proteins. Keratin, for example, makes
up hair and nails. Collagen lends support to ligaments, tendons, and skin.
▪ Enzymes: Enzymes bring reactants together and thereby speed chemical
reactions in cells. They are specific for one particular type of reaction and
only function at body temperature.
- Properties of enzymes:
❖ Most enzymes are proteins.
❖ They are often named for the molecules that they work on,
called substrates.
❖ They are specific to what substrate they work on.
❖ Enzymes have active sites where a substrate binds.
❖ They are not used up in a reaction but instead are recycled.
❖ Enzymes lower the amount of energy of activation needed
❖ Some enzymes are aided by nonprotein molecules called
coenzymes.
▪ Transport: Channel and carrier proteins in the plasma membrane allow
substances to enter and exit cells. Some other proteins transport molecules
in the blood of animals; hemoglobin in red blood cells is a complex protein
that transports oxygen.

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 ▪ Defense: Antibodies are proteins. They combine with foreign substances,
called antigens. In this way, they prevent antigens from destroying cells and
upsetting homeostasis.
▪ Hormones: Hormones are regulatory proteins. They serve as intercellular
messengers that influence the metabolism of cells. The hormone insulin
regulates the content of glucose in the blood and in cells. The presence of
growth hormone determines the height of an individual.
▪ Motion: The contractile proteins actin and myosin allow parts of cells to
move and cause muscles to contract. Muscle contraction facilitates the
movement of animals from place to place.
o The structures and functions of vertebrate cells and tissues (weefsels) differ
according to the type of proteins they contain.
o Proteins are macromolecules with amino acid subunits (proteins are made of
subunits, called amino acids). The central carbon atom in an amino acid bonds to a
hydrogen atom and to three other groups of atoms.
▪ The name amino acid is appropriate because one of these groups is an —
NH2 (amino group) and another is a —COOH (carboxyl group, an acid). The
third group is the R group for an amino acid.
▪ Amino acids differ according to their particular R group.
- The R groups range in complexity from a single hydrogen atom to a
complicated ring compound.
- Some R groups are polar and some are not.
▪ The covalent bond between two amino acids is called a peptide bond. When
three or more amino acids are linked by peptide bonds, the chain that results
is called a polypeptide.
o Shape of proteins
▪ Proteins cannot function unless they have a specific shape. When proteins
are exposed to extremes in heat and pH, they undergo an irreversible change
in shape called denaturation. Once a protein loses its normal shape, it is no
longer able to perform its usual function.
- Researchers recognize that a change in protein shape is responsible
for diseases such as Alzheimer disease and Creutzfeldt–Jakob disease
(the human form of mad cow disease).
o Levels of protein organisation
▪ At least three levels of organization but can have four levels.
- The first level, called the primary structure, is the linear sequence of
the amino acids joined by peptide bonds. Each particular polypeptide
has its own sequence of amino acids.
- The secondary structure of a protein comes about when the
polypeptide takes on a certain orientation in space. Hydrogen
bonding is possible between the C=O of one amino acid and the N—
H of another amino acid in a polypeptide. Coiling of the chain results
in an α (alpha) helix, or a right-handed spiral, and a folding of the
chain results in a β (beta) pleated sheet. Hydrogen bonding between
peptide bonds holds the shape in place.
- The tertiary structure of a protein is its final, three-dimensional
shape. In enzymes, the polypeptide bends and twists in different
ways. In most enzymes, the hydrophobic portions are packed on the

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 inside and the hydrophilic portions are on the outside, where they
can make contact with water.
❖ The tertiary structure of the enzymes determines the types
of molecules with which they will interact.
❖ The tertiary shape of a polypeptide is maintained by various
types of bonding between the R groups; covalent, ionic, and
hydrogen bonding all occur. Some proteins have only one
polypeptide; others have more than one polypeptide, each
with its own primary, secondary, and tertiary structures.
- These separate polypeptides are arranged to give these proteins a
fourth level of structure, termed the quaternary structure.
Hemoglobin is a complex protein having a quaternary structure;
many enzymes also have a quaternary structure.
❖ Each of four polypeptides in hemoglobin is tightly associated
with a nonprotein heme group. A heme group contains an
iron (Fe) atom that binds to oxygen; in that way, hemoglobin
transports O2 to the tissues.

1.3.4 Nucleic acids

• Nucleic acids
o Each cell has a storehouse of information that specifies how a cell should function,
respond to the environment, and divide to make new cells. Nucleic acids, which are
polymers of nucleotides, store information, include instructions for life, and conduct
chemical reactions.
o Two types of nucleic acids are important in the storage and processing of the genetic
information.
▪ DNA (deoxyribonucleic acid) is the type of nucleic acid that not only stores
information about how to copy, or replicate, itself but also specifies the
order in which amino acids are to be joined to make a protein.
▪ RNA (ribonucleic acid) is a diverse type of nucleic acid that has multiple uses.
- Messenger RNA (mRNA) is a temporary copy of a gene in the DNA
that specifies what the amino acid sequence will be during the
process of protein synthesis.
- Transfer RNA (tRNA) is also necessary in synthesizing proteins and
helps translate the sequence of nucleic acids in a gene into the
correct sequence of amino acid during protein synthesis.
- Ribosomal RNA (rRNA) works as an enzyme to form the peptide
bonds between amino acids in a polypeptide. A wide range of other
RNA molecules also perform important functions within the cell.
▪ Not all nucleotides are made into DNA or RNA polymers. Some nucleotides
are directly involved in metabolic functions in cells. For example, some are
components of coenzymes, nonprotein organic molecules that help regulate
enzymatic reactions.
- ATP (adenosine triphosphate) is a nucleotide that stores large
amounts of energy needed for synthetic reactions and for various
other energy-requiring processes in cells.

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• How the structures of DNA and RNA differ
o Nucleotide structure
▪ Each nucleotide is a molecular complex of three types of subunit
molecules—phosphate (phosphoric acid), a pentose (5-carbon) sugar, and a
nitrogen-containing base.
▪ The nucleotides in DNA contain the
sugar deoxyribose, and the nucleotides
in RNA contain the sugar ribose; this
difference accounts for their respective
names.
▪ There are four different types of bases
in DNA: adenine (A), thymine (T),
guanine (G), and cytosine (C). The base
can have two rings (adenine or
guanine) or one ring (thymine or cytosine). In RNA, the base uracil (U)
replaces the base thymine.
- These structures are called bases because their presence raises the
pH of a solution.
o DNA and RNA structure
▪ DNA is double-stranded, with the two strands twisted about each other in
the form of a double helix. In DNA the two strands are held together by
hydrogen bonds between the bases.
- When coiled, DNA resembles a spiral staircase. When unwound, it
resembles a stepladder.
- The uprights (sides) of the ladder are made entirely of phosphate
and sugar molecules, and the rungs of the ladder exhibit
complementary base pairing.
- Thymine (T) always pairs with adenine (A), and guanine (G) always
pairs with cytosine (C). Complementary bases have shapes that fit
together.
❖ Complementary base pairing allows DNA to replicate in a
way that ensures that the sequence of bases will remain the
same. This is important because it is the sequence of bases
that determines the sequence of amino acids in a protein.
▪ RNA is single-stranded. When RNA forms, complementary base pairing with
one DNA strand passes the correct sequence of bases to RNA. RNA is the
nucleic acid directly involved in protein synthesis.

• ATP: an energy carrier

o In addition to being the subunits of nucleic acids, nucleotides have metabolic
functions. When adenosine (adenine plus ribose) is modified by the addition of three
phosphate groups instead of one, it becomes ATP (adenosine triphosphate), which is
an energy carrier in cells.
o Structure of ATP suits its function
▪ ATP is a high-energy molecule, because the last two phosphate bonds are
unstable and easily broken. Usually in cells, the last phosphate bond is
hydrolysed, leaving the molecule ADP (adenosine diphosphate) and a
molecule of inorganic phosphate.

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▪ The energy released by ATP breakdown is used by the cell to synthesize
macromolecules, such as carbohydrates and proteins. In muscle cells, the
energy is used for muscle contraction; in nerve cells, it is used for the
conduction of nerve impulses. After ATP breaks down, it can be recycled by
adding P to ADP.

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2. Cell structure and function (hoofdstuk 3 handboek)
2.1 What is a cell?
2.2 How cells are organised

• Organisation of cells
o Biologists classify cells into two broad categories—the prokaryotes and eukaryotes.
▪ The primary difference between a prokaryotic cell and a eukaryotic cell is the
presence or absence of a nucleus, a membrane-bound structure that houses
the DNA.
▪ Prokaryotic cells lack a nucleus, whereas eukaryotic cells possess a nucleus.
The prokaryotic group includes two groups of bacteria, the eubacteria and
the archaebacteria.
▪ Within the eukaryotic group are the animals, plants, and fungi, as well as
some single-celled organisms called protists.

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 ▪ Despite their differences, both types of cells have a plasma membrane, an
outer membrane that regulates what enters and exits a cell.
- The plasma membrane is a phospholipid bilayer—a “sandwich”
made of two layers of phospholipids. Their polar phosphate
molecules form the top and bottom surfaces of the bilayer, and the
nonpolar lipid lies in between.
- The phospholipid bilayer is selectively permeable, which means it
allows certain molecules—but not others—to enter the cell.
- Proteins scattered throughout the plasma membrane play important
roles in allowing substances to enter the cell.
▪ All types of cells also contain cytoplasm, which is a semifluid medium that
contains water and various types of molecules suspended or dissolved in the
medium. The presence of proteins accounts for the semifluid nature of the
cytoplasm.
- The cytoplasm of a eukaryotic cell contains organelles, internal
compartments that have specialized functions. Originally the term
organelle referred to only membranous structures, but we will use it
to include any well-defined subcellular structure.
- Eukaryotic cells have many types of organelles. Organelles allow for
the compartmentalization of the cell. This keeps the various cellular
activities separated from one another.

• Evolutionary history of the eukaryotic cell

o The first cells on earth were prokaryotic cells.
▪ Today these cells are represented by the bacteria and archaea, which differ
mainly by their chemistry.
o Evidence widely supports the hypothesis that eukaryotic cells evolved from the
archaea. The internal structure of eukaryotic cells is believed to have evolved as the
series of events.

2.3 The plasma membrane and how substances cross it

• Plasma membrane
o Like all cells, a human cell is surrounded by an outer plasma membrane.
▪ The plasma membrane marks the boundary between the outside and the
inside of the cell.
▪ The integrity and function of the plasma membrane are necessary to the life
of the cell.
o It is a phospholipid bilayer with attached or embedded proteins.
▪ A phospholipid molecule has a polar head and nonpolar tails.
▪ When phospholipids are placed in water, they naturally form a spherical
bilayer.
- The polar heads, being charged, are hydrophilic (attracted to water).
❖ They position themselves to face toward the watery
environment outside and inside the cell.
- The nonpolar tails are hydrophobic (not attracted to water).
❖ They turn inward toward one another, where there is no
water.

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 ▪ At body temperature, the phospholipid bilayer is a liquid. It has the
consistency of olive oil. The proteins are able to change their position by
moving laterally (lateraal).
o The fluid-mosaic model is a working description of membrane structure.
▪ It states that the protein molecules form a shifting pattern within the fluid
phospholipid bilayer. Cholesterol lends support to the membrane.

• Plasma membrane functions

o The plasma membrane isolates the interior of the cell from the external
environment.
▪ In doing so, it allows only certain molecules and ions to enter and exit the
cytoplasm freely. Therefore, the plasma membrane is said to be selectively
permeable.
- Small, lipid-soluble molecules, such as oxygen and carbon dioxide,
can pass through the membrane easily.
❖ The small size of water molecules allows them to freely cross
the membrane by using protein channels called aquaporins.
- Ions and large molecules cannot cross the membrane without more
direct assistance, which will be discussed later.
o Diffusion
▪ Diffusion is the random movement of molecules from an area of higher
concentration to an area of lower concentration, until they are equally
distributed.
▪ It is a passive way for molecules to enter or exit a cell. No cellular energy is
needed to bring it about.
o Osmosis
▪ Osmosis is the net movement of water across a selectively permeable
membrane.
▪ The direction by which water will diffuse is determined by the tonicity of the
solutions inside and outside the cell.
- Tonicity is based on dissolved particles, called solutes, within a
solution. The higher the concentration of solutes in a solution, the
lower the concentration of water, and vice versa.
- Typically water will diffuse from the area that has less solute (low
tonicity, and therefore more water) to the area with more solute
(high tonicity, and therefore less water).
▪ Normally body fluids are isotonic to cells. There is the same concentration of
nondiffusible solutes and water on both sides of the plasma membrane.
- Therefore, cells maintain their normal size and shape. Intravenous
solutions given in medical situations are usually isotonic.
▪ Solutions that cause cells to swell or even to burst due to an intake of water
are said to be hypotonic. A hypotonic solution has a lower concentration of
solute and a higher concentration of water than the cells.
- If red blood cells are placed in a hypotonic solution, water enters the
cells. They swell to bursting.
❖ Lysis is used to refer to the process of bursting cells.
❖ Bursting of red blood cells is termed hemolysis.

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 ▪ Solutions that cause cells to shrink or shrivel due to loss of water are said to
be hypertonic. A hypertonic solution has a higher concentration of solute
and a lower concentration of water than do the cells.
- If red blood cells are placed in a hypertonic solution, water leaves
the cells; they shrink. The term crenation refers to red blood cells in
this condition. These changes have occurred due to osmotic
pressure: it controls water movement in our bodies.
o Facilitated transport
▪ During facilitated transport, a molecule is transported across the plasma
membrane from the side of higher concentration to the side of lower
concentration.
- This is a passive means of transport, because the cell does not need
to expend energy to move a substance down its concentration
gradient.
o Active transport
▪ During active transport, a molecule is moving from an area of lower to an
area of higher concentration.
- Active transport requires a protein carrier and the use of cellular
energy obtained from the breakdown of ATP. When ATP is broken
down, energy is released.
❖ In this case, the energy is used to carry out active transport.
Proteins involved in active transport often are called pumps.
o Bulk transport
▪ Cells use bulk transport to move large molecules, such as polysaccharides or
polypeptides, across the membrane.
- These processes use vesicles (blaasjes) rather than channel or
transport proteins.
- During endocytosis, a portion of the plasma membrane invaginates,
or forms a pouch, to envelop a substance and fluid. Then the
membrane pinches off to form an endocytic vesicle inside the cell.
❖ Some white blood cells are able to take up pathogens
(diseasecausing agents) by endocytosis. This process is given
a special name: phagocytosis. Usually cells take up small
molecules and fluid, and then the process is called
pinocytosis.
- During exocytosis, a vesicle fuses with the plasma membrane as
secretion (secretie) occurs.

2.4 The nucleus and endomembrane system

The nucleus contains the genetic instructions that are necessary for the manufacture of the proteins
that are involved in most cellular functions. The endomembrane system is a series of membrane
organelles that function in the processing of materials for the cell.

• The nucleus
o The nucleus, a prominent structure in eukaryotic cells, stores the genetic information
as DNA organized into linear structures called chromosomes.
▪ Located on the chromosome are collections of genes. Genes are segments of
DNA that contain information for the production of specific proteins.

15
 - These proteins have many functions in cells, and they help
determine a cell’s specificity.
- While every cell in the body contains the same genes, cells vary in
which genes are turned on and off, and this enables them to perform
their function in the tissue or organism.
▪ Chromatin is the combination of DNA molecules and proteins that make up
the chromosomes.
- The chromosomes are responsible for transmitting genetic
information from one generation to the next.
- Chromatin can coil (oprollen) tightly to form visible chromosomes
during cell division.
- Most of the time, however, the chromatin is uncoiled (ontrold).
❖ While uncoiled, the individual chromosomes cannot be
distinguished and the chromatin appears grainy in electron
micrographs of the nucleus.
- Chromatin is surrounded by a semifluid medium called the
nucleoplasm. A difference in pH suggests that nucleoplasm has a
different composition than cytoplasm.
- Micrographs of a nucleus often show a dark region (or sometimes
more than one) of chromatin. This is the nucleolus, where ribosomal
RNA (rRNA) is produced.
❖ This is also where rRNA joins with proteins to form the
subunits of ribosomes.
o The nucleus is separated from the cytoplasm by a double membrane known as the
nuclear envelope. This is continuous with the endoplasmic reticulum (ER), a
membranous system of saccules and channels, discussed in the next section.
▪ The nuclear envelope has nuclear pores of sufficient size to permit the
passage of ribosomal subunits out of the nucleus and proteins into the
nucleus.

• Ribosomes
o Ribosomes are organelles composed of proteins and rRNA.
▪ Ribosomes are often attached to the endoplasmic reticulum, but they also
may occur free within the cytoplasm, either singly or in groups called
polyribosomes.
▪ Proteins synthesized at ribosomes attached to the endoplasmic reticulum
have a different destination from that of proteins manufactured at
ribosomes free in the cytoplasm.

• The endomembrane system

o The endomembrane system consists of the nuclear envelope, the endoplasmic
reticulum, the Golgi apparatus, lysosomes, and vesicles (= tiny, membranous sacs).
▪ The endoplasmic reticulum (ER)
- It has two portions.
❖ Rough ER is studded with ribosomes on the side of the
membrane that faces the cytoplasm.

16
 ➢ The proteins that are synthesized at these ribosomes
enter the interior of the ER for additional processing
and modification.
❖ The smooth ER is continuous with the rough ER, but it does
not have attached ribosomes.
➢ Smooth ER synthesizes the phospholipids and other
lipids that occur in membranes.
➢ It also has various other functions, depending
on the particular cell.
- The ER forms transport vesicles in which large molecules are
transported to other parts of the cell.
❖ Often these vesicles are on their way to the plasma
membrane or the Golgi apparatus.
▪ The Golgi apparatus (het golgi apparaat)
- It consists of a stack of slightly curved saccules, whose appearance
can be compared to a stack of pancakes.
- Here proteins and lipids received from the ER are modified.
- The vesicles that leave the Golgi apparatus move to other parts of
the cell.
❖ Some vesicles proceed to the plasma membrane, where they
discharge their contents.
- In all, the Golgi apparatus is involved in processing, packaging, and
secretion.
▪ Lyosomes
- Lysosomes, membranous sacs produced by the Golgi apparatus,
contain hydrolytic enzymes.
- They are found in all cells of the body but are particularly numerous
in white blood cells that engulf disease-causing microbes.
o This system compartmentalizes the cell, so that chemical reactions are restricted to
specific regions. The vesicles transport molecules from one part of the system to
another.

2.5 The cytoskeleton, cell movement and cell junctions

• The cytoskeleton
o The cytoplasm of the cell is crisscrossed by several types of protein fibers, collectively
called the cytoskeleton.
▪ The cytoskeleton helps maintain a cell’s shape and either anchors the
organelles or assists in their movement, as appropriate.
o In the cytoskeleton, microtubules are much larger than actin filaments.
▪ Each is a cylinder that contains rows of a protein called tubulin.
▪ The regulation of microtubule assembly is under the control of a microtubule
organizing centre called the centrosome.
▪ Microtubules help maintain the shape of the cell and act as tracks along
which organelles move.
▪ During cell division, microtubules form spindle fibres (vezels), which assist in
the movement of chromosomes.
▪ Actin filaments, made of a protein called actin, are long, extremely thin
fibres that usually occur in bundles or other groupings.

17
 - Actin filaments are involved in movement. Microvilli, which project
from certain cells and can shorten and extend, contain actin
filaments.
▪ Intermediate filaments, as their name implies, are intermediate in size
between microtubules and actin filaments.
- Their structures and functions differ according to the type of cell.

• Cilia and flagella

o Cilia (sing., cilium) and flagella (sing., flagellum) are involved in movement.
▪ They are made of microtubules.
- Cilia are about 20 times shorter than flagella.
▪ The ciliated cells that line our respiratory tract sweep back up the throat the
debris trapped within mucus. This helps keep the lungs clean.
▪ Similarly, ciliated cells move an egg along the uterine tube, where it may be
fertilized by a flagellated sperm cell.

• Junctions between cells

o Human tissues are known to have junctions between their cells that allow them to
function in a coordinated manner. There are three main types of cell junctions in
human cells.
▪ Adhesion junctions mechanically attach adjacent cells. In these junctions,
the cytoskeletons of two adjacent cells are interconnected.
- They are a common type of junction between skin cells.
▪ In tight junctions, connections between the plasma membrane proteins of
neighboring cells produce a zipperlike barrier.
- These types of junctions are common in the digestive system and the
kidney, where it is necessary to contain fluids (digestive juices and
urine) within a specific area.
▪ Gap junctions serve as communication portals between cells. In these
junctions, channel proteins of the plasma membrane fuse, allowing easy
movement between adjacent cells.

2.6 Metabolism and energy reactions

• Metabolic pathways
o Cellular respiration is an important component of metabolism, which includes all the
chemical reactions that occur in a cell. Often metabolism requires metabolic
pathways and is carried out by enzymes sequentially arranged in cells:

▪ The letters, except A and G, are products of the previous reaction and the
reactants for the next reaction.
▪ A represents the beginning reactant, and G represents the final product. The
numbers in the pathway refer to different enzymes.
▪ Each reaction in a metabolic pathway requires a specific enzyme. The
mechanism of action of enzymes has been studied extensively, because
enzymes are so necessary in cells.

18
 ▪ Metabolic pathways are highly regulated by the cell. One type of regulation
is feedback inhibition.
- In feedback inhibition, one of the end products of the metabolic
pathway interacts with an enzyme early in the pathway. In most
cases this feedback slows down the pathway, so that the cell does
not produce more product than it needs.

• Enzymes
o Enzymes are metabolic assistants that speed up the rate of a chemical reaction.
o The reactant(s) that participate(s) in the reaction is/ are called the enzyme’s
substrate(s).
o Enzymes have a specific region, called an active site, where the substrates are
brought together so they can react.
▪ An enzyme’s specificity is caused by the shape of the active site.
o Coenzymes are nonprotein molecules that assist the activity of an enzyme and may
even accept or contribute atoms to the reaction.
▪ It is interesting that vitamins are often components of coenzymes.

• Mitochondria and cellular respiration

o Mitochondria (sing., mitochondrion) are often called the powerhouses of the cell.
▪ The mitochondria convert the chemical energy of glucose products into the
chemical energy of ATP molecules.
▪ In the process, mitochondria use up oxygen and give off carbon dioxide.
- Therefore, the process of producing ATP is called cellular
respiration.
▪ The structure of mitochondria is appropriate to the task.
- The inner membrane is folded to form little shelves called cristae.
These project into the matrix, an inner space filled with a gel-like
fluid.
- The matrix of a mitochondrion contains enzymes for breaking down
glucose products. ATP production then occurs at the cristae.
❖ They produce energy in the form of ATP
- The structure of a mitochondrion supports the hypothesis that
mitochondria were originally prokaryotes that became engulfed by a
cell.
❖ Mitochondria are bound by a double membrane, as a
prokaryote would be if it were taken into a cell by
endocytosis.
▪ Mitochondria have their own genes—and they reproduce themselves!
o After blood transports glucose and oxygen to cells, cellular respiration begins. It
involves the production of ATP in a cell.
▪ Cellular respiration breaks down glucose to carbon dioxide and water.
▪ Three pathways are involved in the breakdown of glucose: glycolysis, the
citric acid cycle, and the electron transport chain.
- Glycolysis
❖ Means sugar splitting
❖ Is found in almost every type of cell
❖ Is an anaerobic pathway, because it doesn’t need oxygen.

19
 ❖ During glycolysis, hydrogens and electrons are removed from
glucose, and NADH results. The breaking of bonds releases
enough energy for a net yield of two ATP molecules.
- Citric acid cycle, also called the Krebs cycle
❖ Is a cyclical series of enzymatic reactions that occurs in the
matrix of mitochondria.
❖ The purpose is to complete the breakdown of glucose by
breaking the remaining C—C bonds.
- Electron transport chain
❖ NADH molecules from glycolysis and the citric acid cycle
deliver electrons to the electron transport chain.
❖ The members of the electron transport chain are carrier
proteins grouped into complexes.
➢ These complexes are embedded in the cristae of a
mitochondrion.
❖ Each carrier of the electron transport chain accepts two
electrons and passes them on to the next carrier. The
hydrogens carried by NADH molecules will be used later.
➢ High-energy electrons enter the chain, and as they
are passed from carrier to carrier, the electrons lose
energy.
➢ Low-energy electrons emerge from the chain.
❖ Oxygen serves as the final acceptor of the electrons at the
end of the chain.
➢ After oxygen receives the electrons, it combines with
hydrogens and becomes water.
➢ The presence of oxygen makes the electron
transport chain aerobic.
➢ Oxygen does not combine with any substrates during
cellular respiration.
➢ Breathing is necessary to our existence, and the sole
purpose of oxygen is to receive electrons at the end
of the electron transport chain.
❖ The energy, released as electrons pass from carrier to
carrier, is used for ATP production

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3. Organisation and regulation of body systems (hoofdstuk 4 handboek)
3.1 Types of tissues
• Types of tissues
o Tissue—a collection of cells of the same type that perform a common function.
o There are 4 major tissue types in the body:
▪ Connective tissue (bindweefsel)—binds and supports body parts (organs, …).
▪ Muscular tissue (spierweefsel)—moves the body and its parts.
▪ Nervous tissue (zenuwweefsel)—conducts nerve impulses.
▪ Epithelial tissue (epitheel weefsel)—covers body surfaces; lines body
cavities.

3.2 Connective tissue connects and supports

• Connective tissue
o Has three main components: specialized cells,
ground substance, and protein fibers.
▪ Ground substance (Grondsubstantie):
is noncellular material between the
cells.
- Varies in consistency from
solid (bone) to fluid (blood).
o There are three types of protein fibers:
▪ Collagen fibers—flexible and strong.
▪ Reticular fibers—thin, highly branched
collagen fibers.
▪ Elastic fibers—contain elastin, a protein that stretches and recoils.
o There are three main types of connective tissue: fibrous, supportive, and fluid.
▪ Fibrous connective tissue.
- Comes in two main forms: loose and dense.
❖ Both contain fibroblasts separated by matrix (ground
substance and fibers).
❖ Loose fibrous connective tissue.
➢ Includes areolar connective tissue, reticular
connective tissue and adipose tissue.
➢ Loose fibrous connective tissue supports epithelium
and many internal organs.
» Adipose tissue stores fat.
» Has very little extracellular matrix.
» Adipocytes—cells filled with liquid fat.
» Functions in energy storage, insulation and
cushioning.
» Found primarily under the skin and around
some organs.
❖ Dense fibrous connective tissue.
➢ Found in tendons (connect muscles to bones) and
ligaments (connect bones to bones).
➢ Dense fibrous connective tissue contains densely
packed collagen fibers.

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 ▪ Supportive connective tissue.
- Two major types: cartilage and bone.
❖ Cartilage (kraakbeen).
➢ Chondrocytes—cells that lie in small spaces called
lacunae.
➢ Matrix is solid but flexible.
➢ Lacks a direct blood supply, so heals slowly.
➢ 3 types, distinguished by the type of fibers found in
the matrix:
» Hyaline cartilage—fine collagen fibers.
 Found in the tip of the nose, ends of
long bones and the fetal skeleton.
» Elastic cartilage—lots of elastic fibers.
 Found in the outer ear.
» Fibrocartilage—strong collagen fibers.
 Found in the disks between
vertebrae.
❖ Bone
➢ The most rigid connective tissue.
➢ Matrix is made of collagen and calcium salts.
➢ There are two types of bone tissue: compact and
spongy.
- Functions in structure, shape, protection, and leverage for
movement.
▪ Fluid connective tissue
- There are two types of fluid connective tissue: blood and lymph.
❖ Blood.
➢ Made of a fluid matrix called plasma and cellular
components called formed elements.
» 3 formed elements:
 Red blood cells (erythrocytes)—cells
that carry oxygen.
 White blood cells (leukocytes) —
cells that fight infection.
 Platelets (thrombocytes)—pieces of
cells that clot blood.
❖ Lymph.
➢ Derived from the fluid surrounding the tissues.
➢ Contains white blood cells.
➢ Lymphatic vessels absorb excess interstitial fluid and
return lymph to the cardiovascular system.

3.3 Muscular tissue moves the body

• Muscular tissue moves the body
o Muscular tissue.
▪ Specialized to contract.
▪ It is composed of cells called muscle fibers, which contain actin and myosin
filaments.

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 - The interaction of these filaments accounts for movement
▪ Three types: skeletal, smooth, and cardiac.
- Skeletal muscle (also called voluntary muscle) is attached by tendons
to the bones of the skeleton.
❖ When it contracts, body parts move.
❖ Contraction of skeletal muscle is under voluntary control and
occurs faster than in the other muscle types.
- Smooth muscle (also called visceral muscle) is so named because the
cells lack striations (strepen).
❖ It is involuntary, meaning that it is not under conscious
control.
❖ It is found in the walls of viscera (intestine, bladder, and
other internal organs) and blood vessels.
❖ It contracts more slowly than skeletal muscle but can remain
contracted for a longer time.
- Cardiac muscle is found only in the walls of the heart.
❖ Its contraction pumps blood and accounts for the heartbeat.
❖ Cardiac muscle combines features of both smooth and
skeletal muscle.
➢ Like skeletal muscle, it has striations, but the
contraction of the heart is involuntary for the most
part.
❖ Cardiac muscle cells also differ from skeletal muscle cells in
that they usually have a single, centrally placed nucleus. The
cells are branched and seemingly fused together.
❖ Cardiac muscle cells are separate, but they are bound end to
end at intercalated disks.
➢ These are areas where folded plasma membranes
between two cells contain adhesion junctions and
gap junctions

3.4 Nervous tissue communicates

• Nervous tissue
o It consists of nerve cells, called neurons, and neuroglia, the cells that support and
nourish the neurons.
▪ A neuron is a specialized cell that has three parts: dendrites, a cell body, and
an axon.
- A dendrite is an extension that receives signals from sensory
receptors or other neurons.
- The cell body contains most of the cell’s cytoplasm and the nucleus.
- An axon is an extension that conducts nerve impulses.
❖ Long axons are covered by myelin, a white, fatty substance.
❖ Fiber is here referred to an axon along with it myelin sheath,
if it has one. Outside the brain and spinal cord, fibers bound
by connective tissue form nerves.
➢ Nerves conduct signals from sensory receptors to
the spinal cord and the brain, where integration, or
processing, occurs.

23
 ➢ They also conduct signals from the spinal cord and
brain to muscles, glands, and other organs. This
triggers a characteristic response from each tissue.
▪ Neuroglia are cells that outnumber neurons nine to one and take up more
than half the volume of the brain.
- Although the primary function of neuroglia is to support and nourish
neurons, research is being conducted to determine how much they
directly contribute to brain function.
- They do not have long extensions (like axons or dendrites). However,
research found that neuroglia communicate among themselves and
with neurons, even without these extensions.
- Examples of neuroglia
❖ Microglia, in addition to supporting neurons, engulf bacterial
and cellular debris.
❖ Astrocytes provide nutrients to neurons and produce a
hormone known as glial-derived neurotrophic factor (GDNF).
❖ Oligodendrocytes form the myelin sheaths around fibers in
the brain and spinal cord.
❖ Outside the brain, Schwann cells are the type of neuroglia
that encircle long nerve fibers and form a myelin sheath.
o It is the central component of the nervous system, which servers three primary
functions: sensory input, integration of data and motor output.

3.5 Epithelial tissue protects

• Epithelial tissue protects
o Epithelial tissue (epithelium, or plural, epithelia).
▪ Made of tightly packed cells that form a continuous layer.
▪ It lines body cavities, covers body surfaces, and is found in glands.
▪ Usually it has a protective function. It can also be modified to carry out
secretion, absorption, excretion, and filtration.
▪ It is anchored to underlying connective tissue by a basement membrane on
one side and is free on the other side.
- A basement membrane is a thin layer of various types of
carbohydrates and proteins.
▪ They are named by their appearance, for the number of cell layers and the
shape of the cells.
o Is either simple or stratified (depends on the way they are stacked (=gestapeld))
▪ Simple epithelium.
- Single layer of cells.
- They are classified according to the cell type:
❖ Simple squamous epithelium.
➢ Single layer of flattened cells.
➢ It is found in the air sacs of lungs and walls of blood
vessels, where it functions in gas exchange.
❖ Simple cuboidal epithelium.
➢ Single layer of cube-shaped cells.
➢ Found in our glands

24
 ➢ It also covers the ovaries and lines kidney tubules,
the portions of the kidney in which urine is formed.
❖ Simple columnar epithelium.
➢ Single layer of column-shaped cells.
➢ It is found in the uterine tubes, where it propels the
egg toward the uterus.
❖ Pseudostratified columnar epithelium.
➢ Because of the location of the nuclei, it appears to
be layered, but this is not true, because every cell
touches the basement membrane.
➢ It often has cilia (trilhaartjes), which move mucus
(slijm) across its surface.
➢ It is found in our trachea (luchtpijp)
▪ Stratified epithelia.
- Multiple layers of cells on top of each other
❖ Only the bottom layer touches the basement membrane.
- Different types
❖ Stratified squamous epithelia
➢ This forms the outer layer of the skin and lines the
mouth and esophagus (slokdarm).

❖ Transitional epithelia.
➢ The tissue changes in response to tension.
➢ It forms the lining of the urinary bladder, the ureters
(the tubes that carry urine from the kidneys to the
bladder), and part of the urethra (the single tube
that carries urine to the outside).

• Glands (klieren)
o Are one or more cells that make and secrete (afscheiden) a product.
o Two types: exocrine and endocrine.
▪ Exocrine glands secrete into ducts (kanalen).
▪ Endocrine glands secrete into the bloodstream; have no ducts.

3.6 Integumentary system

• The integumentary system (= an organ system)
o It contains many different organs that cooperate to carry out a process.
o It includes the skin.
▪ The skin is an organ comprising all four tissue types: epithelial, connective,
muscular, and nervous tissue.
▪ Because the skin has several accessory organs (hair, nails, sweat glands, and
sebaceous glands), it is also sometimes referred to as the integumentary
system.
- Nails are a protective covering of the distal part of fingers and toes,
collectively called digits.
❖ The nails grow from epithelial cells at the base of the nail in
the portion called the nail root.

25
 ❖ The cuticle is a fold of skin that hides the nail root. The
whitish colour of the half-moon-shaped base, or lunula,
results from the thick layer of cells in this area.
❖ The cells of a nail become keratinized as they grow out over
the nail bed.
- Hair follicles begin at a bulb in the dermis and continue through the
epidermis, where the hair shaft extends beyond the skin.
❖ A dark hair colour is largely due to the production of true
melanin by melanocytes present in the bulb.
❖ If the melanin contains iron and sulphur, hair is blond or red.
❖ Greying occurs when melanin cannot be produced, but white
hair is due to air trapped in the hair shaft.
- Each hair follicle has one or more oil glands, also called sebaceous
glands, which secrete sebum.
❖ Sebum is an oily substance that lubricates the hair in the
follicle and the skin.
❖ Acne is an inflammation of the sebaceous glands, which
most often occurs during adolescence due to hormonal
changes.
- Sweat glands, also called sudoriferous glands, are numerous and
present in all regions of skin.
❖ It is a tubule that begins in the dermis and either opens into
a hair follicle or, more often, opens onto the surface of the
skin.
❖ Sweat glands play a role in modifying body temperature:
when body temperature starts to rise, sweat glands become
active. Sweat absorbs body heat as it evaporates. Once the
body temperature lowers, sweat glands are no longer active.
▪ It is the most conspicuous (opvallend) organ system in the body.
▪ The skin has numerous functions:
- It protects underlying tissues from physical trauma, pathogen
invasion, and water loss.
- It also helps regulate body temperature. Therefore, skin plays a
significant role in homeostasis, the relative constancy of the internal
environment.
- The skin even synthesizes certain chemicals that affect the rest of
the body.
- Skin contains sensory receptors, such as touch and temperature
receptors. Thus, it helps us to be aware of our surroundings and to
communicate with others
o Skin has 2 main regions: the epidermis and the dermis.
▪ Epidermis (= thin, outermost layer of the skin)
- It is made up of stratified squamous epithelium.
- New epidermal cells for the renewal of skin are derived from stem
(basal) cells.
❖ The importance of these stem cells is observed when there is
an injury to the skin. If an injury, such as a burn, is deep
enough to destroy stem cells, then the skin can no longer

26
 replace itself. The damaged tissue is removed asap and skin
grafting begins.
➢ Autografting: the skin needed for grafting is usually
taken from other parts of the patient’s body
➢ Allografting: the graft is received from another
person and is sometimes obtained from cadavers.
➢ It can also be grown in the lab and can be
transplanted back to the patient.
- Newly generated skin cells become flattened and hardened as they
push to the surface.
❖ Hardening takes place because the cells produce keratin, a
waterproof protein.
➢ These cells are also called keratinocytes.
» Outer skin cells are dead and keratinized, so
the skin is waterproof. This prevents water
loss and helps maintain water homeostasis.
» It also prevents water from entering the
body when the skin is immersed.
- Two types of specialized cells are located deep in the epidermis.
❖ Langerhans cells are macrophages, white blood cells that
phagocytize infectious agents and then travel to lymphatic
organs.
➢ There they stimulate the immune system to react to
the pathogen.
❖ Melanocytes, lying deep in the epidermis, produce melanin,
the main pigment responsible for skin colour.
➢ People have the same number of melanocytes but
the amount of melanin produced varies, which leads
to variation in the skin colour.
➢ When skin is exposed to the sun, melanocytes
produce more melanin. This protects the skin from
the damaging effects of the ultraviolet (UV) radiation
in sunlight. The melanin is passed to other epidermal
cells, and the result is tanning.
➢ Another pigment, called carotene, is present in
epidermal cells and in the dermis. It gives the skin of
some Asian populations its yellowish hue. The
pinkish colour of fair-skinned people is due to the
pigment haemoglobin in the red blood cells in the
blood vessels of the dermis.
❖ Epidermal cells produce vitamin D when exposed to UV rays.
➢ Vitamin D is important in the regulation of calcium
and phosphorus levels in the body, and those are
important in the proper development and
mineralisation of the bones.

27
 - Skin cancer
❖ Too much ultraviolet radiation is dangerous and can lead to
skin cancer.
➢ Basal cell carcinoma, derived from stem cells gone
awry, is the most common type of skin cancer and is
the most curable.
➢ Melanoma skin cancer derived from melanocytes, is
extremely serious.
▪ The dermis (= thick, inner layer of the skin)
- It is a region of dense fibrous connective tissue beneath the
epidermis.
- It contains collagen and elastic fibers.
❖ The collagen fibers are flexible but offer great resistance to
overstretching. They prevent the skin from being torn.
❖ The elastic fibers maintain normal skin tension but also
stretch to allow movement of underlying muscles and joints.
- Contains blood vessels, sensory receptors, and glands.
❖ The blood vessels nourish the skin
➢ When blood rushes into these vessels, a person
blushes.
❖ Sensory receptors also account for the use of the skin as a
means of communication between people, such as touch,
pressure, pain, hot, and cold.
o A subcutaneous layer, sometimes called the hypodermis, is found between the skin
and any underlying structures, such as muscle or bone.
▪ Technically it is not part of the skin
▪ This layer is composed of loose connective tissue and adipose tissue, which
stores fat.
- Fat is a stored source of energy in the body.
- Adipose tissue helps thermally insulate the body from either gaining
heat from the outside or losing heat from the inside.

3.7 Organ systems, body cavities and body membranes

• Organ systems, body cavities, and body membranes
o Organ — a group of tissues performing a common function.
▪ Groups of organs with a similar function form an organ system
- Some of these organ systems (for example, the respiratory system)
occupy specific cavities; others, (for example, the muscular system)
are found throughout the body.
- The most important organ systems are listed on the picture on the
next page.
▪ Organs and cavities are lined with membranes, many of which secrete fluid.

28
o Body cavities (holtes)
▪ They are divided into two main cavities: ventral cavity and dorsal cavity.
- Ventral cavity.
❖ Contains the thoracic, abdominal, and pelvic cavities.
➢ The thoracic cavity contains the lungs and the heart.
» It is separated from the abdominal cavity by
a horizontal muscle called the diaphragm.
➢ The stomach, liver, spleen, pancreas, and gallbladder
and most of the small and large intestines are in the
abdominal cavity.
➢ The pelvic cavity contains the rectum, the urinary
bladder, the internal reproductive organs, and the
rest of the small and large intestines.
» Males have an external extension of the
abdominal wall called the scrotum, which
contains the testes.
- The dorsal cavity has two parts
❖ The cranial cavity within the skull contains the brain.
❖ The vertebral canal, formed by the vertebrae, contains the
spinal cord.

29
o Body membranes line cavities and the internal spaces of organs and tubes that open
to the outside.
▪ Four types: mucous, serous, and synovial membranes and the meninges.
- Mucous membranes
❖ Line the tubes of the digestive, respiratory, urinary, and
reproductive systems.
❖ They are composed of an epithelium overlying a loose
fibrous connective tissue layer.
❖ The epithelium contains specialized cells that secrete mucus.
➢ Mucus usually protects the walls of the stomach and
small intestine from digestive juices (maagsappen).
This protection breaks down when a person
develops an ulcer (een zweer).
- Serous membranes
❖ Line and support the lungs, the heart, and the abdominal
cavity and its internal organs.
❖ They secrete a watery fluid that keeps the membranes
lubricated.
❖ Serous membranes support the internal organs and
compartmentalize the large thoracic and abdominal cavities.
❖ They have specific names according to their location
➢ The pleurae (sing., pleura) line the thoracic cavity
and cover the lungs.
➢ The pericardium forms the pericardial sac and
covers the heart
➢ The peritoneum lines the abdominal cavity and
covers its organs.
» A double layer of peritoneum, called
mesentery, supports the abdominal organs
and attaches them to the abdominal wall.
» Peritonitis is a life-threatening infection of
the peritoneum.
- Synovial membranes
❖ Composed only of loose connective tissue line the cavities of
freely movable joints.
❖ They secrete synovial fluid into the joint cavity.
➢ This fluid lubricates (smeren) the ends of the bones,
so that they can move freely.
➢ In rheumatoid arthritis, the synovial membrane
becomes inflamed and grows thicker, restricting
movement.
- The meninges
❖ These are membranes within the dorsal cavity.
❖ They are composed only of connective tissue and serve as a
protective covering for the brain and spinal cord.
❖ Meningitis is a life-threatening infection of the meninges.

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3.8 Homeostasis
• Homeostasis
o Is the body’s ability to maintain a relative constancy of its internal environment by
adjusting its physiological processes.
o Even though external conditions may change dramatically, we have physiological
mechanisms that respond to disturbances and limit the amount of internal change.
o Conditions usually stay within a narrow range of normalcy.
▪ For example, blood glucose, pH levels, and body temperature typically
fluctuate during the day, but not greatly.
▪ If internal conditions change to any great degree, illness results.

31
4. Cardiovascular system: heart and blood vessels (hoofdstuk 5 handboek)
4.1 Overview of the cardiovascular system
• The cardiovascular system
o Consist of
▪ The heart, which pumps blood
▪ The blood vessels, through which the blood flows
o Circulation performs exchanges
▪ Even though the circulation of blood depends on the beating of the heart,
the overall purpose of circulation is to service the cells of the body.
- Blood removes waste products from that fluid.
- Blood also provides the interstitial fluid with the oxygen and
nutrients cells require to continue their existence.
▪ At the lungs, blood drops off carbon dioxide and picks up oxygen.
▪ Gas exchange is not the only function of blood.
- Nutrients enter the bloodstream at the intestines and transport
much-needed substances to the body’s cells.
- Blood is purified of its wastes at the kidneys, and water and salts are
retained as needed.
▪ The liver is important, because it takes up amino acids from the blood and
returns needed proteins.
- Liver proteins transport substances such as fats in the blood.
- The liver also removes toxins and chemicals that may have entered
the blood at the intestines, and its colonies of white blood cells
destroy bacteria and other pathogens.
o Functions of the cardiovascular system
▪ Transport: it not only transports oxygen to the cells of the body but also
removes carbon dioxide and other waste products of metabolism.
- It also transports nutrients from the digestive system and hormones
from the endocrine system to the cells of the body.
▪ Protection: it transports the cells of the immune system.
- These cells, and their associated antibodies and chemical signals,
help protect the body from infection.
▪ Regulation: it participates in the homeostasis of a variety of the body’s
conditions, including temperature, pH balance, and water and electrolyte
levels.
o The lymphatic system assists the cardiovascular system, because lymphatic vessels
collect excess interstitial fluid and return it to the
cardiovascular system
o What is the main pathway of blood in the body?
▪ Closed, one directional circuit
▪ 3 layers
- Connective tissue
- Smooth muscle (with elastic
fibers)
- Endothelium

32
4.2 The types of blood vessels
• The cardiovascular system consists of three types of blood vessels— arteries, veins, and
capillaries —that transport blood to and from the tissues of the body.
o The arteries: from the heart
▪ An artery is a blood vessel that transports blood away from the heart.
- The structure of an artery is well suited for the transport of blood
leaving the heart under pressure.
- The arterial wall has three layers:
❖ The innermost of which is a thin layer of cells called
endothelium.
❖ A relatively thick middle layer of smooth muscle and elastic
tissue, which allows an artery to expand and absorb the
pressure.
❖ The artery’s outer layer is connective tissue. The strong
walls of an artery give it support when blood enters under
pressure.
▪ Arterioles are small arteries that regulate blood pressure.
- When the smooth muscles relax, the diameter increase (vaso-
relaxation)
- When the smooth muscles contract, the diameter decrease (vaso-
constriction)

• The capillaries (haarvaten): exchange (zie verder)

o Arterioles branch into capillaries, the
smallest of the blood vessels.
o The structure of a capillary is adapted for
the exchange of materials with the cells of
the body.
o Each capillary is an extremely narrow, microscopic tube with a wall composed only of
endothelium. Capillary endothelium is formed by a single layer of epithelial cells
with a basement membrane.
o Capillary beds (networks of many capillaries) are present in all regions of the body,
so no cell is far from a capillary and thus not far from gas exchange with blood.
▪ Rings of muscle called precapillary sphincters control the blood flow through
a capillary bed.
▪ Constriction of the sphincters closes the capillary bed. When a capillary bed
is closed, the blood moves to an area where gas exchange is needed, going
directly from arteriole to venule through a pathway called an arteriovenous
shunt.

• The veins: to the heart

o Veins are blood vessels that return blood to the heart.
o Venules are small veins that drain blood from the capillaries and then join to form a
vein.
o The walls of both veins and venules have the same three layers as arteries
(endothelium, smooth muscle and elastic tissue, connective tissue).

33
 ▪ However, there is less smooth muscle in the middle layer of a vein and less
connective tissue in the outer layer. Therefore, the wall of a vein is thinner
than that of an artery.
o Because the blood leaving the capillaries is usually under low pressure, veins often
have valves (kleppen), which allow blood to flow only towards the heart when open
and prevent backward flow of blood when closed.
▪ Valves are extensions of the inner wall layer and are found in the veins that
carry blood against the force of gravity, especially the veins of the lower
extremities.

• How can you tell the difference

between an artery and vein?
o Wall composition/thickness
o Inner lumen (diameter)
o Valves

4.3 The heart is a double pump

• The heart
o It is a cone-shaped, muscular
organ located between the lungs, directly behind the sternum (breastbone).
o The heart is tilted, so that the apex (the pointed end) is oriented to the left.
o The heart consists of two big parts
▪ The major portion of the heart is the interior wall of tissue called the
myocardium, consisting largely of cardiac muscle tissue.
- The muscle fibers of myocardium are branched. Each fiber is tightly
joined to neighbouring fibers by structures called intercalated disks.
❖ The intercalated disks also include cell junctions like gap
junctions and desmosomes.
➢ Gap junctions aid in the simultaneous contractions
of the cardiac fibers.
➢ Desmosomes include arrangements of protein fibers
that tightly hold the membranes of adjacent cells
together and prevent overstretching.
▪ The heart is surrounded by the pericardium, a thick, membranous sac that
supports and protects the heart.
- The inside of the pericardium secretes pericardial fluid (a lubrication
fluid), and the pericardium slides smoothly over the heart’s surface
as it pumps the blood.
o Internally, a wall called the septum separates the heart into a right side and a left
side.
o The heart has four chambers:
▪ The two upper, thin-walled atria are called the right and the left atrium.
- Each atrium has a wrinkled, earlike flap on the outer surface called
an auricle.
▪ The two lower chambers are the thick-walled ventricles, called the right
ventricle and the left ventricle.

34
 o Heart valves
▪ The valves that lie between the atria and the ventricles are called the
atrioventricular (AV) valves.
- These valves are supported by strong, fibrous strings called chordae
tendineae, which are attached to papillary muscles that project from
the ventricular walls.
- The chordae anchor the valves, preventing them from inverting
when the heart contracts.
- The AV valve on the right side is called the tricuspid valve, because it
has three flaps, or cusps.
- The AV valve on the left side is called the bicuspid valve, because it
has two flaps.
❖ The bicuspid valve is commonly referred to as the mitral
valve, because it has a shape like a bishop’s hat, or miter.
▪ The remaining two valves are the semilunar valves, with flaps shaped like
half-moons.
- These valves lie between the ventricles and their attached vessels.
- The semilunar valves are named for their attached vessels:
❖ The pulmonary semilunar valve lies between the right
ventricle and the pulmonary trunk.
❖ The aortic semilunar valve lies between the left ventricle
and the aorta.

• Coronary circulation: the hearts blood supply

o The myocardium – the middle, muscular layer of the three layers of the walls of the
heart—receives oxygen and nutrients from the coronary arteries.
▪ The coronary arteries serve the heart muscle itself.
▪ These arteries are the first branches off the aorta.
- They originate just above the aortic semilunar valve. They lie on the
exterior surface of the heart, where they divide into diverse
arterioles.
▪ The coronary capillary beds join to form venules, which converge to form
the cardiac veins, which empty into the right atrium.
- Because they have a very small diameter, they can become easily
clogged, leading to coronary artery disease. If these vessels become
completely clogged, oxygen and nutrients such as glucose will not
reach the muscles of the heart. This may result in a myocardial
infarction, or heart attack.
o Likewise, wastes are removed by the cardiac veins.
o The blood that flows through the heart contributes
little to either nutrient supply or waste removal.

• Passage of blood through the heart

o By sending electrical signals between cells, both
atria and then both ventricles contract
simultaneously.
o For a concrete trace of the path: book!

35
• Conclusion
o The heart is a double pump, because the right ventricle of the heart sends blood
through the lungs and the left ventricle sends blood throughout the body. Thus, the
left ventricle has the harder job of pumping blood.
o Valves control blood flow
o Muscles contract in sequence (wave) for optimal pump effect
o The arteries are more muscular than veins to withstand the higher pressure exerted
on them.
o The veins have a thinner wall and a larger center to contain blood (reserve).

4.4 Features of the cardiovascular system

• Blood flow is regulated
o Blood pressure moves blood in arteries
▪ Blood pressure is the pressure of blood against the wall of a blood vessel.
- The highest arterial pressure, called the systolic pressure, is reached
during ejection of blood from the heart.
- The lowest arterial pressure, called the diastolic pressure, occurs
while the heart ventricles are relaxing.
- High blood pressure is called hypertension, and low blood pressure
is called hypotension.
❖ Both systolic and diastolic blood pressure decrease with
distance from the left ventricle, because the total cross-
sectional area of the blood vessels increases — there are
more arterioles than arteries.
❖ The decrease in blood pressure causes the blood velocity
(snelheid) to gradually decrease as it flows toward the
capillaries.
o Blood flow is slow in the capillaries
▪ This is important because the slow progress allows time for the exchange of
substances between the blood in the capillaries and the surrounding tissues.
▪ Any needed changes in flow rate are adjusted by the opening and closing of
the precapillary sphincters.
o Blood flow in veins returns blood to heart
▪ The velocity of blood flow increases from capillaries to veins.
▪ Blood pressure plays only a small role in returning venous blood to the heart.
▪ Venous return is dependent on three additional factors:
- The skeletal muscle pump, dependent on skeletal muscle contraction
❖ The skeletal muscle pump functions
every time a muscle contracts. When
skeletal muscles contract, they
compress the weak walls of the veins.
This causes the blood to move past a
valve.
- The respiratory pump, dependent on breathing
(inhaling, exhaling)
- Valves in veins

36
4.5 Two cardiovascular pathways
• The blood flows in two major circuits
o The pulmonary circuit, which circulates blood through
the lungs (exchanges of gases)
▪ Starting at the right atrium, we can trace the
path of blood in the body. The right atrium
collects blood from the systemic circuit of the
body. The blood then passes into the right
ventricle, which pumps it into the pulmonary
trunk. The pulmonary trunk divides into the
right and left pulmonary arteries, which branch
as they approach the lungs. The arterioles take
blood to the pulmonary capillaries, where
carbon dioxide is given off and oxygen is picked
up. Blood then passes through the pulmonary
venules, which lead to the four pulmonary veins
that enter the left atrium.
▪ Blood in the pulmonary arteries is oxygen-poor
but blood in the pulmonary veins is oxygen-rich,
so it is not correct to say that all arteries carry
blood high in oxygen and all veins carry blood
low in oxygen.
o The systemic circuit, which serves the needs of body
tissues (exchanges with interstitial fluid)
▪ The largest artery in the systemic circuit, the
aorta, receives blood from the heart
▪ The largest veins, the superior and inferior venae cavae (sing., vena cava),
return blood to the heart.
- The superior vena cava collects blood
from the head, the chest, and the
arms
- The inferior vena cava collects blood
from the lower body regions.
- Both enter the right atrium.
o [Coronary circulation – blood supply to the heart
(muscles)]
▪ This is a third one, but less important

• Hepatic portal system: specialized for blood filtration

o The hepatic portal vein drains blood from the capillary beds of the digestive tract to
a capillary bed in the liver.
▪ The term portal indicates that it lies between two capillary beds.
o The blood in the hepatic portal vein is oxygen-poor but is rich in glucose, amino
acids, and other nutrients absorbed by the small intestine.
o The liver stores glucose as glycogen, and it either stores amino acids or uses them
immediately to manufacture blood proteins.
▪ The liver also purifies the blood of toxins and pathogens that have entered
the body by way of the intestinal capillaries.

37
 ▪ After blood has filtered slowly through the liver, it is collected by the hepatic
vein and returned to the inferior vena cava.

4.6 Exchange at the capillaries

• Exchange at the capillaries
o Two forces control the movement of fluid through the capillary wall
▪ Blood pressure, which tends to cause fluids in the blood to move from
capillary to tissue spaces
▪ Osmotic pressure, which tends to cause water to move in the opposite
direction.
o Midway along the capillary, where blood pressure is lower, the two forces essentially
cancel each other, and there is no net movement of fluid.
▪ Solutes now diffuse according to their concentration gradient:
- Oxygen and nutrients (glucose and amino acids) diffuse out of the
capillary
- Carbon dioxide and wastes diffuse into the capillary

4.7 Cardiovascular disorders

• Why should we care about cardiovascular disease?
o Cardiovascular disease (CVD) is the most common cause of death in the Western
world.
▪ 31% deaths are due to CVD (heart attacks, strokes)
▪ Blood vessel and or heart

• Disorders of the blood vessels

o Hypertension (high blood pressure)
▪ Occurs when blood moves through the arteries at a higher pressure than
normal.
- Hypertension: resting BP >130/85 mmHg
- Many risk factors! Age, lifestyle, genetics
❖ Narrowing of diameter of arterioles
❖ Reduced flexibility of arterioles
▪ It is a silent killer because there are few symptoms
▪ It increases workload for heart and arteries
- Heart attack, stroke

38
 ▪ It is often seen in individuals who have atherosclerosis.
- Atherosclerosis is caused by the formation of lesions (damage of the
tissue), or atherosclerotic plaques, on the inside of blood vessels.
❖ The plaques narrow blood vessel diameter, choking off blood
and oxygen supply to the tissues.
▪ It leads to thickening of heart muscles (less flexible, less effective)
▪ How to treat hypertension? Decrease pressure by
- Decreasing blood volume (diuretics)
- Decreasing effect of (stress) hormones (betablockers)
- Increasing vasorelaxation (ACE inhibitors)
- Decreasing formation of atherosclerosis (reducing cholesterol)
- Reducing stress, lifestyle changes etc.
o Atherosclerosis (zie eerder, hierboven)
▪ Is an injury (lesion) of the blood
vessel wall
▪ It is build-up of plaque (fat,
cholesterol, calcium, etc.)
▪ It causes narrowing of blood vessel:
- Partial blockage of passage:
angina pectoris
❖ This leads to choking off blood and oxygen supply to the
tissues
❖ Silent or with angina (pain)
➢ Triggers
➢ Symptoms:
» Chest pain or discomfort (centre/left chest)
» Pressure, squeezing, fullness, pain,
indigestion
» Upper body discomfort
» Pain in arms, back, shoulder, neck, jaw
» Shortness of breath
- Complete block of passage: heart attack or myocardial infarction
❖ Part of myocardium dies due to lack of oxygen
▪ Injuries on blood vessel wall trigger blood clot formation (platelets , fibrin,…)
- Clot that is stationary is called a thrombus
- Embolus is when it detaches and can move to distant sites.
- Stroke, heart attack
▪ Weakening of the blood vessel wall can lead to aneurysm
▪ How to treat atherosclerotic plaque in coronary arteries
- Coronary bypass surgery
❖ Grafted vessels (e.g., saphenous vein)
- Balloon angioplasty
❖ Placing of stent
o Stroke (cerebrovascular accident (CVA))
▪ Often results when a small cranial arteriole bursts or is blocked by an
embolus.
▪ Lack of oxygen causes a portion of the brain to die, and paralysis or death
can result.

39
 ▪ A person is sometimes forewarned of a stroke by a feeling of numbness in
the hands or the face, difficulty in speaking, or temporary blindness in one
eye.
o Heart attack (myocardial infarction (MI))
▪ It occurs when a portion of the heart muscle dies due to lack of oxygen.
- If a coronary artery becomes partially blocked, the individual may
then suffer from angina pectoris.
▪ Characteristic symptoms of angina pectoris include a feeling of pressure,
squeezing, or pain in the chest. Pressure and pain can extend to the left arm,
neck, jaw, shoulder, or back.
- Nausea and vomiting, anxiety, dizziness, and shortness of breath
may accompany the chest discomfort.
▪ Nitro-glycerine or related drugs dilate blood vessels and help relieve the
pain.
▪ When a coronary artery is completely blocked, perhaps because of a
thromboembolism, a heart attack occurs.
o Aneurysm
▪ It is a ballooning of a blood vessel, most often the abdominal artery or the
arteries leading to the brain.
▪ Atherosclerosis and hypertension can weaken a vessel and cause ballooning.
▪ Treatment
- Medication to lower blood pressure
- Surgery, stents

• Disorders of the heart

o Heart failure
▪ Heart cannot pump enough blood to meet body’s need
- Heart does not fill properly during diastole
- Heart does not contract forcefully enough
▪ Symptoms:
- Shortness of breath, trouble breathing, fatigue, fluid build-up such as
swelling ankles, feet, legs, etc.
▪ Treatment
- Medication to lower BP or reduce blood volume
- Surgery (LVAD: left ventricle assist device)
- Heart transplant
o Arrhythmia
▪ A problem with the rate or rhythm of your heartbeat. It means that your
heart beats too quickly, too slowly, or with an irregular pattern.
▪ When the heart beats faster than normal, it is called tachycardia.
▪ When the heart beats too slowly, it is called bradycardia.

40
5. Cardiovascular system: blood (hoofdstuk 6 handboek)
5.1 An overview: blood
• Functions of blood
o The functions of blood fall into three general categories: transport, defense, and
regulation.
▪ Blood is the primary transport medium.
- It transports oxygen, dioxide, wastes, nutrients, hormones, …
▪ Blood defends the body against pathogen invasion and blood loss.
- An antibody is a protein that combines with and disables specific
pathogens. Disabled pathogens can then be destroyed by the
phagocytic white blood cells.
- When an injury occurs, blood clots and defends against blood loss.
Blood clotting involves platelets and proteins.
▪ Blood plays an important role in regulating the body’s homeostasis.
- It helps regulate body temperature by picking up heat, mostly from
active muscles, and transporting it about the body.
- If the body becomes too warm, blood is transported to dilated blood
vessels in the skin. Heat disperses to the environment, and the body
cools to a normal temperature.

• Composition of blood
o Blood is a tissue and, like any tissue, it contains cells and cell fragments. Collectively
the cells and cell fragments are called the formed elements. The cell and cell
fragments are suspended in a liquid called plasma. Therefore, blood is classified as a
liquid connective tissue.
▪ Formed elements
- Consist of red blood cells, white blood cells, and platelets and are
produced in red bone marrow.
❖ Red blood cells = erythrocytes (RBCs)
❖ White blood cells = leukocytes (WBCs)
❖ Platelets = thrombocytes
- Red bone marrow contains pluripotent stem cells, the parent cells
that divide and give rise to all the types of blood cells
▪ Plasma
- Is the liquid medium for carrying various substances in the blood.
❖ It also distributes the heat generated as a by-product of
metabolism, particularly muscle contraction.
- It consists of 91% water and 9% salts (ions) and organic molecules.
❖ These salts are dissolved in the plasma and, along with
plasma proteins, help maintain the osmotic pressure of
blood.
❖ Salts also function as buffers that help maintain blood pH
- The most abundant organic molecules in blood are called the plasma
proteins (mostly produced in the liver).
❖ The plasma proteins have many functions that help maintain
homeostasis.

41
 ❖ Three major types of plasma proteins
➢ Albumins – most abundant and important for
plasma’s osmotic pressure as well as transport
» They also combine with and help transport
other organic molecules
➢ Globulins – also important in transport and gamma
globulins are known as our antibodies!
» 3 types: α-, β-, γ- globuline
➢ Fibrinogen is an inactive plasma protein. Once
activated, fibrinogen forms a blood clot.
• Origin of blood cells

5.2 Red blood cells and transport of oxygen

• Red blood cells (RBCs), also known as erythrocytes
o The presence of haemoglobin in these cells, and their unique internal structure,
makes them a unique cell type in the body.
▪ Haemoglobin (Hb)
- Oxyhemoglobin: oxygen bound to Hb
❖ In lungs
- Deoxyhemoglobin: after oxygen is released
❖ In tissue
- Carbaminohemoglobin: CO 2 binds to Hb
❖ Removing carbon dioxide from tissue
o They are also very abundant; there are 4 to 6 million red blood cells per microliter
(μl) of whole blood.

42
• How RBCs carry oxygen
o Red blood cells are highly specialized for oxygen (O2) transport.
o RBCs contain haemoglobin (Hb), a pigment with a high affinity (attraction) for
oxygen.
▪ Hb is also responsible for the red coloration of RBCs and the blood.
o Each haemoglobin molecule can transport 4 molecules of O2, and each RBC contains
about 280 million haemoglobin molecules.
▪ This means that each red blood cell can carry over a billion molecules of
oxygen

• Production of red blood cells

o RBCs are produced in the red bone marrow from stem cells
o The structure of a RBC is well suited to its function in the body.
▪ As red blood cells mature, they acquire haemoglobin and lose their nucleus
and other internal organelles.
▪ The lack of internal organelles means that RBCs are incapable of conducting
many of the functions of other eukaryotic cells in the body.
▪ Also, due to their lack of a nucleus, RBCs are unable to replenish important
proteins and repair cellular damage.
- Therefore, red blood cells live only about 120 days. When they age,
red blood cells are phagocytized by white blood cells (macrophages)
in the liver and spleen.
o The body has a way to boost the number of RBCs when insufficient oxygen is being
delivered to the cells: the kidneys release a hormone called erythropoietin (EPO),
which stimulates the stem cells in bone marrow to produce more red blood cells.
▪ The liver and other tissues also produce EPO for the same purpose.

• Disorders involving RBCs

o If the liver fails to excrete it, heme accumulates in tissues, causing a condition called
jaundice.
▪ The skin and whites of the eyes turn yellow (neonatal jaundice)
o Anaemia appears when there is an insufficient number of red blood cells or the cells
do not have enough haemoglobin
▪ The individual has a tired, run-down feeling.
▪ Different types of anaemia
- Iron-deficiency anaemia is the most common form.
❖ It results from an inadequate intake of dietary iron, which
causes insufficient haemoglobin synthesis.
- A lack of vitamin B12 causes pernicious anaemia, in which stem cell
activity is reduced due to inadequate DNA production.
- Folic-acid deficiency anaemia also leads to a reduced number of
RBCs, particularly during pregnancy.
- Haemolysis is the rupturing of red blood cells.
❖ In haemolytic anaemia, the rate of red blood cell destruction
increases.
- Sickle cell disease is a hereditary condition in which the individual
has sickle-shaped red blood cells, which tend to rupture as they pass
through the narrow capillaries.

43
5.3 White blood cells and defence against disease
• White blood cells (leukocytes)
o They differ from red blood cells in that they are usually larger, have a nucleus, lack
haemoglobin, and are translucent unless stained.
o White blood cells are not as numerous as red blood cells; there are only 5,000–
11,000 per microliter (μl of blood).
o White blood cells are derived from stem cells in the red bone marrow, where most
types mature.
o There are several types of white blood cells, and the production of each type is
regulated by a protein called a colony-stimulating factor (CSF).
▪ In a person with normally functioning bone marrow, the numbers of white
blood cells can double within hours, if needed.
o White blood cells fight infection; thus, they are an important part of the immune
system.
▪ The immune system, consists of a variety of cells, tissues, and organs that
defend the body against pathogens, cancer cells, and foreign proteins.
▪ White blood cells have various ways to fight infection
- Some white blood cells produce antibodies, proteins that combine
with antigens.
❖ An antigen is a cell or other substance foreign to the
individual that invokes an immune response.
o Many white blood cells live only a few days; often they die while fighting pathogens.
Others live for months or even years.

• Types of white blood cells

o White blood cells are classified as either granular leukocytes or agranular
leukocytes.
▪ Granular leukocytes have noticeable cytoplasmic granules, which can be
easily seen when the cells are stained and examined with a microscope.
- Granules contain various enzymes and proteins.
- They include neutrophils, eosinophils, and basophils.
❖ Neutrophils have a multilobed nucleus, so they are called
polymorphonuclear leukocytes, or “polys.”
➢ Compared to other granular leukocytes, the granules
of neutrophils are not easily stained with either
acidic red dye or basic purple dye.
➢ They are usually first responders to bacterial
infection, and their intense phagocytic activity is
essential to overcoming an invasion by a pathogen.
➢ Neutrophils, and other types of white blood cells
such as the macrophages, have the ability to
squeeze through pores in the capillary wall;
therefore, they are also found in interstitial fluid and
lymph.
❖ Eosinophils have a bilobed nucleus.
➢ Their large, abundant granules take up eosin and
become a red colour.

44
 ➢ They are involved in the protection of the body
against large parasites (the parasitic worms) and the
phagocytosis of the allergens and proteins
associated with the inflammatory response.
❖ Basophils are the rarest of the white blood cells, but they
play an important role in the immune response.
➢ They have a U-shaped or lobed nucleus. Their
granules take up the basic stain and become a dark-
blue colour.
➢ Mast cells (such as basophils) release histamine
associated with allergic reactions.
▪ Agranular leukocytes contain only sparse, fine granules, which are not easily
viewed under a microscope.
- They include the lymphocytes and the monocytes. Lymphocytes and
monocytes do not have granules but do have non-lobular nuclei.
They are sometimes called the mononuclear leukocytes.
❖ Lymphocytes are responsible for specific immunity to
particular pathogens and toxins (poisonous substances).
➢ The lymphocytes are of two types: B cells and T cells.
» Mature B cells called plasma cells produce
antibodies, the proteins that combine with
target pathogens and mark them for
destruction.
» Some T cells (cytotoxic T cells) directly
destroy pathogens. The AIDS virus attacks
one of several types of T cells. In this way,
the virus causes immune deficiency, an
inability to defend the body against
pathogens.
❖ Monocytes are the largest of the white blood cells.
➢ After taking up residence in the tissues, they
differentiate into even larger macrophages. In the
skin, they become dendritic cells.

• Disorders involving WBCs

o Some immune deficiencies can be inherited, such as severe combined
immunodeficiency (SCID)
▪ When the stem cells of white blood cells lack an enzyme called adenosine
deaminase.
- Without this enzyme, B and T lymphocytes do not develop and the
body cannot fight infections.
▪ Treatment
- Injections of the missing enzyme can be given twice weekly
- Bone marrow transplant
❖ Bone marrow contains multipotent stem cells
❖ Matching donor needed, based on genetic profile
- Gene therapy to replace malfunctioning gene

45
 o Leukemia: a group of cancers that involve uncontrolled white blood cell proliferation
▪ Therefore, they are incapable of performing their normal defense functions.
o Infectious mononucleosis – “kissing disease”
▪ Occurs when the Epstein-Barr virus (EBV) infects lymphocytes resulting in
fatigue, sore throat, and swollen lymph nodes
▪ Spreads via saliva (speeksel)

• What do leukocytes look like?

5.4 Platelets and blood clotting

• Platelets (thrombocytes)
o They result from fragmentation of large cells, called megakaryocytes, in the red bone
marrow.
o About 200 billion platelets are made per day.
o These formed elements are involved in the process of blood clotting, or coagulation.
▪ The blood-clotting process helps the body maintain homeostasis in the
cardiovascular system by ensuring that the plasma and formed elements
remain within the blood vessels.
▪ Platelets and the injured tissues release a clotting factor called prothrombin
activator, which converts prothrombin in the plasma to thrombin.
▪ After the blood clots, a yellowish fluid called serum escapes from the clot. It
contains all the components of plasma except fibrinogen and prothrombin.

• Disorders related to blood clotting (coagulation)

o Hemophilia (bleeding disorder)
▪ Caused by a deficiency of one or more clotting proteins
- Hemophilia A—lack of factor VIII
❖ Today, Factor VIII can be made by genetic engineering to
supplement hemophiliacs
- Hemophilia B –lack of factor IX (“Royal” disease)

46
 o Thrombocytopenia
▪ When there is an insufficient number of platelets
o Thrombosis (obstructive clotting)
▪ Obstruction of blood vessels by a blood clot (thrombus)
o Embolism
▪ Lodging of an embolus (blood clot) inside a blood vessel and blocking it
o Some medications interfere with hemostasis (= reduce blood clotting)
▪ Aspirin
▪ Warfarin (rat poison)

5.5 Blood typing and transfusions

• Human blood types
o The term blood type refers to variations in the surface proteins that are found on the
surface of red blood cells (RBCs).
▪ These proteins play an important role in blood transfusions, or the transfer
of blood from one individual to another.
- For transfusions to be done safely, blood must be typed, so that
agglutination (clumping of red blood cells) does not occur when
blood from different people is mixed.
❖ Blood typing usually involves determining the ABO blood
group and whether the individual is Rh-negative (Rh– ) or Rh-
positive (Rh+).

• ABO blood groups

o Terminology to understand ABO blood typing
▪ Antigen – a foreign (non-self) marker, often a
polysaccharide or a protein, that stimulates an
immune response
- Epitope: part of the antigen that is
recognized by immune system
▪ Antibody – a protein made in response to an
antigen binding specifically to that
antigen/epitope
o Only certain types of blood transfusions are safe, because
the plasma membranes of red blood cells carry
glycoproteins that can be antigens to other individuals.
o ABO blood typing is based on the presence or absence of
two possible antigens, called type A antigen and type B
antigen.
▪ Whether these antigens are present or not
depends on the inheritance of the individual.
o Blood compatibility
▪ Blood compatibility is very important when
transfusions are done. The antibodies in the
plasma must not combine with the antigens on
the surface of the red blood cells or else
agglutination occurs.

47
 ▪ With agglutination, anti-A antibodies have combined with type A antigens,
and anti-B antibodies have combined with type B antigens.
- Therefore, agglutination is expected if the donor has type A blood
and the recipient has type B blood.
▪ Type O blood is sometimes called the universal donor, because the red
blood cells of type O blood lack A and B antigens.
- Type O donor blood should not agglutinate with any other type of
recipient blood.
▪ Likewise, type AB blood is sometimes called universal recipient blood,
because the plasma lacks A and B antibodies.
- Type AB recipient blood should not agglutinate with any other type
of donor blood.

• Rh blood groups
o The designation of blood type usually also includes whether the person has or does
not have the Rh factor on the red blood cell.
▪ Rh-negative individuals normally do not have antibodies to the Rh factor, but
they make them when exposed to the Rh factor.
o Rh (D) factor positive or negative (e.g., O+, A+; AB-)
o Exposure to Rh+ blood can trigger antibody production in Rh- people
▪ Pregnancy: hemolytic disease of the newborn
- Pregnancy in RH- mothers
❖ During birth, foetal Rh-positive red blood cells leak across
placenta into mother's blood stream. Mother forms anti-Rh
antibodies that cross the placenta and attack foetal Rh+ red
blood cells. During the next pregnancy, the maternal
immune system quickly produces antibody against the
foetus RBC. The foetus is attacked.
- The Rh problem is prevented by giving Rh-negative women an Rh
immunoglobulin injection no later than 72 hours after giving birth to
an Rh-positive child.
❖ This injection contains anti-Rh antibodies that attack any of
the baby’s red blood cells in the mother’s blood before these
cells can stimulate her immune system to produce her own
antibodies.
❖ Called RhoGAM, this treatment does not harm the new-
born’s red blood cells; however, the treatment is not
beneficial if the woman has already begun to produce
antibodies.
➢ Therefore, the timing of the injection is most
important.

48
• Homeostasis
o The picture summarizes how the organ systems of the body interact with the
cardiovascular system to maintain homeostasis.

49
6. Lymphatic and immune system (hoofdstuk 7 handboek)
6.1 The lymphatic system
• The lymphatic system
o Consists of lymphatic vessels and the lymphatic organs.
o Has 4 main functions that contribute to homeostasis:
▪ Fluid transport: Lymphatic capillaries absorb excess tissue fluid and return it
to the bloodstream.
▪ Lipid transport: Lymphatic capillaries (lacteals) in the small intestine absorb
fats associated with proteins and transport them to the bloodstream
▪ Immune defense: it is responsible for the production, maintenance, and
distribution of lymphocytes in the body.
▪ It helps in defense against
pathogens.

• Components of the lymphatic system (see

picture)
o Lymphatic duct
o Lymphatic nodes
o Tonsil, adenoids
o Red bone marrow
o Thymus
o Spleen

• Lymphatic vessels
o Lymphatic vessels form a one-way system of capillaries to vessels and, finally, to
ducts.
▪ These vessels take lymph to cardiovascular veins in the shoulders.
o The fluid inside lymphatic vessels is called lymph.
▪ Lymph is usually a colourless liquid, but after a meal it appears creamy
because of its lipid content.
o The lymphatic capillaries join to form lymphatic vessels that merge before entering
either the thoracic duct or the right lymphatic duct.
o The construction of the larger lymphatic vessels is similar to that of cardiovascular
veins, including the presence of valves.
o They pick up bacteria for destruction in lymph nodes.

• Lymphatic organs
o The lymphatic organs are divided into two categories.
▪ The primary lymphatic organs include the red bone marrow and the thymus
▪ The lymph nodes and spleen represent the secondary lymphatic
organs.
o Primary lymphatic organs
▪ Red bone marrow (myeloid tissue)
- Produces all types of blood cells
❖ Stem cells blood cell production!
- It is found in selected bones (by adults, see picture of
skeletal).

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 ▪ Thymus
- Is a soft, bi-lobed gland
- It is largest in children and shrinks as we age (whereas it gets
replaced by fat cells).
- Two functions
❖ It produces thymic hormones, such as thymosin, thought to
aid in the maturation of T lymphocytes.
❖ Immature T lymphocytes migrate from the bone marrow
through the bloodstream to the
thymus, where they mature (and
become T-cells).
➢ Hormone Thymosin regulates
maturation
o Secondary lymphatic organs
▪ Lymph nodes
- Small, bean-shaped structures found along the
lymphatic vessels
- Filled with B cells, T cells, and macrophages
- Common in the neck, armpit, and groin regions
- They filter lymph to lymphocytes and those
identify and fight infection
▪ Spleen
- Largest lymphatic organ (similar to lymph node)
- They filter blood: removal of RBC, recycling iron
- Connective tissue divides the spleen into regions
❖ White pulp: antibody producing B
lymphocyte
❖ Red pulp: monocytes and macrophages help filtering the
blood

6.2 Innate immune defences

• 3 lines of defence (see next for further explanation)
o Barriers
o Unspecific defence
▪ Protective proteins
▪ Phagocytosis
▪ Inflammation
o Specific defence
▪ Antibody (humoral) mediated immunity
▪ Cell-mediated immunite

• Non-specific and innate immune defenses (yes you are born with it!)
o First line of defense against and infection by pathogens:
▪ Barriers: both physical and chemical
- The skin
❖ The keratin of the skin prevents microbial growth, and the
surface of the skin is constantly being lost to exfoliation
(afschilfering).

51
 ❖ A chemical barrier in the form of secretions of sebaceous
(oil) glands of the skin. This acidic mixture contains chemicals
that weaken or kill certain bacteria on the skin.
- Mucous membranes lining the respiratory,
digestive, reproductive, and urinary tracts are
also physical barriers to entry by pathogens.
❖ The ciliated cells that line the upper
respiratory tract sweep mucus and
trapped particles up into the throat,
where they can be coughed or spit out
or swallowed.
- Perspiration, saliva, and tears contain an
antibacterial enzyme called lysozyme.
- A significant chemical barrier to infection is
created by the normal flora, microbes that
usually reside in the mouth, intestine, and other areas.
o Second line of defense against infections by pathogens:
▪ Protective proteins: complement, interferons
- Complement
❖ Group of blood plasma proteins that help in immune
response
➢ Involved in the inflammatory response by binding to
mast cells, causing them to release histamine
➢ Attract phagocytes to pathogens by binding them
➢ Form a membrane attack complex that makes holes
in some bacteria and viruses, causing them
to burst
- Interferons: communication molecules
❖ These are proteins produced by virus-infected cells
and sent out to warn neighboring healthy cells
➢ Uninfected cells: destroy viral RNA and
reduce protein synthesis
➢ Infected cells: apoptosis (the process of
programmed cell death)
➢ It activates immune cells
▪ Phagocytes and Natural killer cells
▪ Inflammation response

- Five hallmark symptoms are redness, heat, swelling, pain, and loss of
function.

52
6.3 Adaptive immune defences
• Third line of defence: adaptive response
o Adaptive defences overcome an infection by doing away with the particular disease-
causing agent that has entered the body
▪ It helps us protect against specific pathogens when nonspecific defences fail
o Recognition of antigen (non-self markers)
o Helps protect us against cancer
o Depends on the action of lymphocytes
▪ B-cells= Antibody mediated immune response
▪ T-cells = cell mediated immune response (see next)

• Adaptive immune defence: antigen detection

o Antigens are markers of NON-SELF
▪ It is a substance that mobilizes immune system
(epitopes)
▪ Made of proteins, polysaccharides
▪ For example: surface markers on RBC
o Markers of SELF
▪ Made of Major Histocompatibility Complex
(MHC) proteins
▪ (re: blood type markers!)

• Humoral immunity = defence by B cells or antibody-mediated immunity

o B cells are produced with specific ‘detection antennae’ (BCR= B-cell
receptor) during maturation in bone marrow
o Functions of B cells
▪ Antigen recognition (1)
- Antigen binds to specific BCR
▪ B cell activation: cytokines (2)
▪ Clonal expansion (3)
- Plasma cells: antibody production
- Memory cells: retain antigen information
▪ Apoptosis (4)

• Structure of antibodies
o The basic unit that composes antibody molecules is a Y-shaped
protein molecule with two arms.
▪ Each arm has a “heavy” (long) polypeptide chain and a “light” (short)
polypeptide chain.
o 5 classes of antibodies (only 3 types we have to know)
▪ IgG (= main antibody, old infection)
- Presence: main antibody type in
circulation; crosses the placenta
from mother to foetus
- Function: binds to pathogens,
activates complement, and
enhances phagocytosis by white
blood cells

53
 ▪ IgM (fresh infection)
- Presence: antibody type found in circulation; largest antibody; first
antibody formed by a newborn; first antibody formed with any new
infection
- Function: activates complement and clumps cells
▪ IgA (niet kennen)
- Presence: Main antibody type in secretions such as saliva and breast
milk
- Function: Prevents pathogens from attaching to epithelial cells in
digestive and respiratory tracts
▪ IgD (niet kennen)
- Presence: Antibody type found on surface of immature B cells
- Function: Signifies readiness of B cell
▪ IgE (antibody in allergic responses)
- Presence: antibody type found as antigen receptors on mast cells in
tissues
- Function: responsible for immediate allergic response and protection
against certain parasitic worms

• T cell: cell mediated immunity (they directly attack diseased cells and cancer cells)
o T cells are unable to recognize an antigen without help. The
antigen must be displayed to them by an antigen-presenting
cell (APC), such as a macrophage.
▪ Phagocytosis (= proces waarbij kleine deeltjes zoals
bacteriën, parasieten, dode of stervende cellen en ander
lichaamsvreemd materiaal door een cel, een fagocyt, wordt
opgenomen)
▪ Formation of complex with MHC
o MHC: major histocompatibility complex
▪ MHC: marker for self
- Human Leukocyte Antigens (HLA)
▪ Combines with antigen → flag to stimulate cell
mediated immune response
o T cells produced with specific ‘detection antennae’ (TCR= T cell
receptor) during maturation in thymus
▪ Activation: APC + MHC complex (1)
▪ Clonal expansion (2)
- Cytotoxic T cell: perforin and granzyme
❖ Have vacuoles containing granzymes and perforins.
❖ Perforins punch holes in target cells
❖ Granzymes cause the cell to undergo apoptosis.
- T helper cells: producing cytokines
- Memory cells: retain AG information
▪ Apoptosis: programmed cell death (3)
- Apoptosis is programmed cell death.
❖  necrosis (uncontrolled cell death)
- When the infection is over, plasma cells are removed by apoptosis.
❖ Recycling of cell components

54
6.4 Acquired immunity
• Acquired immunity
o Immunity is the ability to combat diseases (pathogens) and cancer.
o It can be brought naturally through an infection or artificially through medical
intervention.
o There are 2 types of immunity, active and passive.
▪ Active immunity
- = Body makes antibodies against a particular antigen.
- Natural infection or through immunization involving vaccines.
- Primary immune response:
❖ First encounter with
antigen → recognition +
clonal expansion of B and
T cells → production of
memory cells
❖ Lag time for AB
production
- Secondary immune response
(booster)
❖ Recognition and clonal expansion
❖ Fast and increased AB production (memory cells)
- This type of immunity is usually long-lasting.
- It depends on the memory of B and T cells.
▪ Passive immunity
- = An individual is given antibodies against a particular antigen.
- This type of immunity is short-lived.
- Naturally:
❖ Pregnancy
❖ Breast feeding
- Antibody injection
❖ Emergency treatment (rabies, hepatitis virus, venomous
bites)
• Vaccination
o Smallpox (pokken)
▪ Serious, contagious sometimes fatal disease
▪ Direct face-face contact
▪ Prodrome: Fever, malaise, aches
▪ Rash: rash > liquid filled bumps,> scab > scar
▪ Four types: severe –mild: fatality rate 30%
▪ Eradicated in 1980 due to a WW vaccination program
o Measles (mazelen)
▪ Highly contagious, airbourne virus 2h infectious
▪ Serious illness, high fever for up to 7d
▪ Runny nose, cough, red & watery eyes
▪ Rash on face/upper neck spreading to limbs
▪ Complications (5<>20y): blindness, encephalitis, diarrhoea, pneumonia
▪ Death 10% of cases (2013: 400 deaths/d)

55
6.5 Hypersensitivity reactions
• How can the immune system harm the body
o Allergies
▪ Hyperreaction of the immune system to an allergen (e.g. dust mites, hay
fever, food allergies)
▪ Hypersensitivity reaction, excessive inflammatory response mediated by IgE
(mast cells, basophils)
- Antigen binds to IgE -> activates mast cells/basoph to release
histamine
- Localized: affect only the area exposed
❖ Runny nose/eyes (hayfever), itchy rash (contact allergy)
- Systemic: affecting several organ systems
- Bronchoconstriction, vasodilation, increased capillary leakage
▪ Anaphylatic shock
- Severe systemic allergic reaction
❖ To food, insect bites/stings, medication
- Fast onset and life threatening
❖ Massive release of inflammatory mediators (histamine)
❖ Symptoms: swelling, itching, difficulty breathing, vomiting,
circulatory collapse, low blood pressure
- Emergency: Epinephrine injection (counters shock)-> vasoconstrictor
+ increase of heartbeat
o Tissue rejection
▪ Organ transplantation: donor organs
- MHC foreign (human leukocyte antigens (HLA))
▪ Tissue rejection can occur when cytotoxic T cells respond to tissue that is not
recognized as “self.”
▪ This can be controlled by giving patients immunosuppressive drugs and by
transplanting organs that have the same (or very similar) MHC proteins in
the donor and recipient.
▪ Organs lacking HLA grown in lab
o Immune system disorders (auto-immune diseases)
▪ Autoimmune disease
- Defective recognition of “self”
- Multiple sclerosis, myasthenia gravis, and rheumatoid arthritis,
- Neuropsychiatric systemic lupus erythematosus
❖ Redness in face, pain, fever, fatigue, neuro-psychiatric
symptoms (schizophrenia, anxiety, depression, cognitive
impairment)
▪ Immunodeficiency disease
- A disease in which the immune system is compromised and thus
unable to defend the body against disease
- Examples: AIDS and SCID

56
7. Biology of infectious diseases (hoofdstuk 8 handboek)
• Introduction
o Poliomyelitis (Polio)
o CNS => paralysis
o Before 1955: >15 000/y (US)
o Jonas Salk and Albert Sabin
o 1957: 80-90% drop in new cases

7.1 Bacteria and viruses

• How do microbes and humans interact?
o Microbes are microscopic organisms, that are very abundant (overvloedig), both in
the environment and as inhabitants of our bodies.
▪ Microbiome: 10x more bacterial cells than own cells
o We use microbes to make many foods and we even use them to make drugs.
o Microbes are important as decomposers to recycle nutrients.
o Some microbes cause disease in humans; we call these pathogens.

• What are microbes?

o Microbes are microscopic organisms and particles that include bacteria, viruses,
prions, and other organisms such as fungi (candida albicans), multicellular parasites
(worms)…

• How do the sizes of our cells, bacteria, and viruses compare?

• What are bacteria?

o Single-celled, prokaryotes that do not have a nucleus.
o They have a plasma membrane and are (often) protected by a
cell wall.
o Motile bacteria usually have long, very thin appendages called
flagella (sing., flagellum).
▪ The flagella rotate 360° and cause the bacterium to
move backward.
o Some bacteria have fimbriae, stiff fibers that allow the
bacteria to adhere to surfaces such as host cells.
▪ Fimbriae allow a bacterium to cling to and gain access
to the body.

57
 o In contrast, a pilus is an elongated, hollow appendage used to transfer DNA from one
cell to another.
▪ Genes that allow bacteria to be resistant to antibiotics can be passed
between bacterial cells through a pilus by a process called conjugation.
o DNA is packaged in a single chromosome arranged in a plasmid
o Some bacteria have accessory rings of DNA called plasmids (antibiotic resistance).
o Ribosomes
o Bacteria reproduce by a process called binary fission, resulting in 2 cells that are
identical to the original cell.

• What are viruses

o Viruses are small, nonliving, acellular (= not composed of cells) parasites
o They bridge the gap between the living and the non-living.
o Outside a host, viruses are essentially chemicals that can be stored on a shelf.
▪ But when the opportunity arises, viruses replicate inside cells, and during this
period they clearly appear to be alive.
o They reproduce inside of a host cell.
▪ No cell organelles
o All viruses have an outer protein coat (capsid) and nucleic acid (RNA or DNA) inside.
o Some viruses have an envelope (which is part of host cell membrane).
o Viruses are specific to which cell type they will attach to and enter.

• What are prions?

o Prions are infectious misfolded protein particles
o They cause degenerative disease of the nervous system, also called wasting diseases:
▪ Bovine spongiform encephalitis (BSE, “mad cow disease”)
▪ Creutzfeld-Jacob disease (CJD)

7.2 Infectious diseases and human health

• Infectious diseases, can be classified as:
o Epidemic: there are more cases of the disease than expected in a certain area for a
certain period
o Outbreak: the epidemic is confined to a local area
o Pandemic: a global epidemic

• Determination of Health Risk

o Transmissibility: how easily it is passed from person to person
o Mode of transmission: respiratory, fecal–oral, body fluids
o Virulence: how much damage is caused by the infection

• History of HIV: human immunodeficiency virus

o Origins in Africa: HIV was originally found in nonhuman primates (monkeys) and may
have mutated.
o Exact dates of the first human cases are still being investigated.
o The first documented death in the US was in 1969.
o HIV was found to be the cause of AIDS in 1983-1984.

58
• Immune deficiency
o AIDS: acquired immune deficiency syndrome
▪ Infection by the human immunodeficiency virus (HIV)
▪ It is a retrovirus, it must use reverse transcription to convert its RNA into
viral DNA.
o HIV targets specific immune cells
o Retrovirus attaches to CD4 receptors on the surface of a helper T cell or macrophage
o Transmission: via body fluids (i.e. blood, semen, breast milk, vaginal secretions)

• Structure of HIV (see pictures on the right)

o It consists of two single strands of RNA, various proteins and an
envelope with spikes (Gp120)
o Carries 3 enzymes
▪ Reverse transcriptase catalyses reverse transcription, the
conversion of the viral RNA to viral DNA.
▪ Integrase catalyses the integration of viral DNA into the
DNA of the host cell.
▪ Protease catalyses the breakdown of the newly
synthesized viral polypeptides into functional viral
proteins.

• HIV life cycle: 3 categories

o Category A, acute Phase:
▪ Asymptomatic but highly
infectious (high viral
load), initially low
antibody count
▪ CD4 count above 500
cells/mm3
▪ Flu like symptoms,
functioning immune
system
▪ Production of CD4 =
destruction of CD4
o Category B, chronic Phase:
▪ Symptoms related to impaired immune system (herpes lesions, diarrhea,
fever, dysplasia)
▪ HIV virus load increases
▪ CD4 count between 200-499 cells/mm3
o Category C, AIDS:
▪ Opportunistic infections that eventually cause death
- Fungal (pneumocystis), bacterial (mycobacterium), parasites
(toxoplasmosis), cancer (Kaposi sarcoma)
▪ Increasing viral load
▪ CD4 count has fallen below 200 cells/mm 3

59
• Transmission and prevention of HIV
o Transmission is through sexual contact, dirty needles, a blood transfusion, or to a
baby from the mother.
o Globally, heterosexual sex is the most common mode of transmission.
o HIV is not passed through casual contact.
o Prevention is through abstinence, sex with only one uninfected partner, and proper,
consistent use of condoms!

• HIV testing and treatment

o HIV tests detect antibodies, virus antigen/RNA.
o Most people develop antibodies within 2-8 weeks of infection, but it can take 3-6
months
o Treatments:
▪ Drug therapy: Highly active antiretroviral therapy (HAART) uses a
combination of drugs to inhibit HIV replication.
▪ Vaccines: Scientists have studied more than 50 different preventive vaccines
and 30 therapeutic vaccines.

• Science Focus: AIDS vaccines

o Difficulties in vaccine development:
▪ No vaccine has ever proven to be 100% effective at blocking a virus from
entry into cells.
▪ HIV viruses are genetically different locally and globally.
▪ Vaccines may only provide short-term protection from infection.
▪ There are concerns that the vaccine may increase the chances of getting the
disease or even cause the disease.
▪ HIV inserts its genetic material into human cells and hides from the immune
system.
▪ There is no ideal animal model for testing besides humans themselves.

7.3 Emerging diseases

• Emerging diseases
o An infectious disease may be classified as an emerging disease if
▪ It is occurring for the first time in human populations
▪ It is rapidly increasing in its incidence (or frequency) in humans
▪ It is entering into new geographic regions
o First time in humans
▪ Bird flu, swine flu, SARS, MERS-CoV
o Re-emerging
▪ Plague (yersinia pestis), smallpox
o Increase in cases/correct identification
▪ Microcephaly: ZIKA
▪ Gastric ulcers: helicobacter pylori

7.4 Antibiotic resistance

• Antibiotic resistance
o Some well-known pathogens are becoming more difficult to fight due to the advent
of antibiotic resistance.

60
• And against bacteria…
o Antibiotica
▪ Molecules produced by microorganisms to fight other microorganisms
(bacteria)
▪ Penicillin (Alexander Fleming 1928)
▪ Interfere with:
- Protein synthesis
- Cell wall synthesis
- Damaging cell wall structure
- Metabolism

• Antibiotic resistance
o Penicillin was introduced in 1943.
▪ Four years later, resistant bacteria were noted.
o Antibiotic use does not cause humans to become resistant to the drugs; pathogens
become resistant.
o Resistant strains of the TB bacterium and Staphylococcus aureus are of particular
concern.
▪ Nosocomial infections
o The best way to fight antibiotic resistance is by using antibiotics wisely.

• How does antibiotic resistance develop?

61
8. Digestive system and nutrition (hoofdstuk 9 handboek)
8.1 Overview of digestion
• Digestive system
o The organs of the digestive system are located within a tube called the
gastrointestinal (GI) tract.
o The purpose of the digestive system is to hydrolyse, or break down using water, the
macromolecules found in food to their subunit molecules.
▪ These molecules include carbohydrates, fats, and proteins, which generally
are too large to cross the plasma membrane.
o The main processes in the digestive process
▪ Ingestion – intake of food via the mouth
▪ Digestion – mechanically or chemically breaking down foods into their
subunits
- Mechanical digestion occurs primarily by chewing in the mouth and
by wavelike contractions of the smooth muscles in the stomach.
- During chemical digestion, digestive enzymes hydrolyse our food’s
macromolecules into absorbable subunits. It begins in the mouth,
continues in the stomach, and is completed in the small intestine.
▪ Movement – food must be moved along the GI tract in order to fulfill all
functions
▪ Absorption – movement of nutrients across the GI tract wall to be delivered
to cells via the blood
▪ Elimination – removal of indigestible molecules

• An overview of the digestive system

62
• Wall of the digestive tract
o We can compare the GI tract to a garden hose that has a beginning (mouth) and an
end (anus).
o The lumen is the open area of a hollow organ or vessel and in the GI tract is the
central space that contains food being digested.
o The wall of the GI tract has four layers.
▪ Each layer can be associated with a particular function and disorder.
- The inner layer of the wall next to the lumen is called the mucosa.
❖ The mucosal layer contains cells that produce and secrete
mucus used to protect all the layers of the tract from the
digestive enzymes inside the lumen.
❖ Diverticulosis is a condition in which portions of the mucosa
of any part of the GI tract—but primarily the large
intestine—have pushed through the other layers and formed
pouches (zakjes), where food can collect.
- The second layer in the GI wall is called the submucosa.
❖ The submucosal layer is a broad band of loose connective
tissue that contains blood vessels, lymphatic vessels, and
nerves.
➢ These are the vessels that will carry the nutrients
absorbed by the mucosa.
❖ Lymph nodules, called Peyer patches, are also in the
submucosa. Like the tonsils, they help protect us from
disease.
❖ The submucosa contains blood vessels, so it can be the site
of an inflammatory response that leads to inflammatory
bowel disease (IBD).
➢ Chronic diarrhoea, abdominal pain, fever, and
weight loss are symptoms of IBD.
- The third layer is termed the muscularis.
❖ It contains two layers of smooth muscle.
➢ The inner, circular layer encircles the tract.
➢ The outer, longitudinal layer lies in the same
direction as the tract.
❖ The contraction of these muscles, under nervous and
hormonal control, accounts for peristalsis and subsequent
movement of digested food from the oesophagus to the
anus.
o Visualizing the layers of the GI tract
▪ See picture on the right

63
8.2 The mouth, pharynx and oesophagus
• The GI tract
o The mouth, the pharynx and the oesophagus are in the upper portion of the GI tract

• The mouth (also called the oral cavity)

o It receives food and begins the process of mechanical and chemical digestion.
o The roof of the mouth separates the nasal cavities from the oral cavity.
▪ The roof has two parts
- An anterior (toward the front) hard palate
- A posterior (toward the back) soft palate
o Three pairs of salivary glands secrete salivary amylase that begins carbohydrate
digestion.
▪ 3 salivary glands produce saliva
- All three glands connect to the oral cavity via ducts.
- Saliva moistens food, making it easier to chew and swallow
▪ Saliva contains
- Mucin: mucus-like protein holding food particles for easy swallowing
- Salivary amylase: cleaving carbohydrates into smaller pieces
- Bicarbonate (HCO3 -): maintains the pH of the mouth between 6.5
and 7.5
- Lysozyme: inhibits bacterial growth
o Tonsils at the back of the mouth are lymphatic tissues, that are important in fighting
diseases.
o The mouth contains teeth that begin the mechanical breakdown of food.
o The tongue is covered in taste buds and also assists in the mechanical breakdown
and movement of food.
o The tongue forms a bolus (mass of chewed food) and moves it toward the pharynx (a
hollow space at the back of the throat).

• Swallowing: delivering food to stomach

o Step 1: voluntary phase
▪ The oesophagus is a muscular tube that moves food into
the stomach, because other possible avenues are blocked.

o Step 2: Involuntary phase

64
• Peristalsis
o Pushes food forward
o Lump of food (bolus) stretches a portion of the GI tract
▪ In front of bolus: smooth muscle relax
▪ Behind bolus: muscles contract.
o Peristaltic wave of contraction
▪ Mixing the contents of the stomach
▪ Pushing the contents of the esophagus and intestines
forward

8.3 The stomach and small intestine

• The stomach
o Is a thick-walled, J-shaped organ that lies on the left side of the body beneath the
diaphragm.
o The stomach is continuous with the oesophagus above and the duodenum of the
small intestine below.
o It stores food, initiates the
digestion of protein, and
controls the movement of
food into the small intestine.
▪ Nutrients are not
absorbed by the
stomach.
▪ But it does absorb
alcohol, because
alcohol is fat soluble
and can pass
through membranes
easily.
o The oblique layer also allows the stomach to stretch and to mechanically break
down food into smaller fragments that are mixed with gastric juice.
o The mucosa of the stomach has deep folds called rugae.
▪ These disappear as the stomach fills to an approximate capacity of one liter.
▪ The mucosa of the stomach has millions of gastric pits, which lead into
gastric glands.
- The gastric glands produce gastric juice. Gastric juice contains an
enzyme called pepsin, which digests protein, plus hydrochloric acid
(HCl) and mucus.
❖ HCl causes the stomach to be very acidic with a pH of about
2. This acidity is beneficial, because it kills most bacteria
present in food. Although HCl does not digest food, it does
break down the connective tissue of meat and activates
pepsin.
o When food leaves the stomach, it is a thick, soupy liquid of partially digested food
called chyme.
▪ Chyme’s entry into the small intestine is regulated, so that small amounts
enter at intervals.

65
 ▪ Peristaltic waves move the chyme toward the pyloric sphincter, which closes
and squeezes most of the chyme back, allowing only a small amount to enter
the small intestine at one time

• Small intestine: digestion and absorption

o It is named for its small diameter
o It is a very long tube (~6m), so it has a large surface area for absorption.
o Functions
▪ Digestion
- Neutralizes acid from stomach
- Adds digestive enzymes and bile (gal)
- Breaks proteins, carbohydrates, and lipids to absorbable materials
▪ Absorption
- 95% of nutrients are absorbed in small intestine
o Anatomy of the small intestine

• How are nutrients digested and transported out of the small intestine?
o Carbohydrate is digested to glucose, which is actively transported into the cells of
intestinal villi. From there, glucose moves into the bloodstream.
o Proteins are digested to
amino acids, which are
actively transported into the
cells of intestinal villi. From
there, amino acids move into
the bloodstream.
o Fats are emulsified by bile
and digested to
monoglycerides (glycerol)
and fatty acids. These diffuse
into cells, where they
recombine and join with proteins. These lipoproteins, called chylomicrons, enter a
lacteal.

66
• What are the major digestive enzymes?

8.4 The accessory organs and regulation of secretions

• Accessory organs
o Pancreas
▪ Fish-shaped spongy
organ behind the
stomach
▪ Exocrine function
- Secretes
enzymes into
the small
intestine
❖ Trypsin
digests proteins.
❖ Lipase digests fats.
❖ Pancreatic amylase digests carbohydrates.
- Secretes bicarbonate into the small intestine to neutralize stomach
acids
▪ Endocrine function
- Secretes insulin into the blood to keep blood sugar levels under
control
o Liver
▪ The liver is a large metabolic organ that lies under the diaphragm and is
made of 100,000 lobules.
▪ Functions of the liver
- Storage
❖ Stores iron (Fe2+), the water-soluble vitamin B12, and the
fat-soluble vitamins A, D, E, and K
❖ Stores glucose as glycogen after a meal; breaks down
glycogen to glucose to maintain the glucose concentration of
blood between eating periods
- Production
❖ Makes plasma proteins, such as albumins and fibrinogen,
from amino acids
❖ Produces urea after breaking down amino acids

67
 ❖ Helps regulate blood cholesterol level, converting some to
bile salts
- Detox
❖ Destroys old red blood cells; excretes bilirubin, a breakdown
product of hemoglobin in bile, a liver product
❖ Detoxifies blood by removing and metabolizing poisonous
substances
o Gallbladder

• Endocrine and nervous systems regulate digestion

8.5 The large intestine and defecation

• The large intestine
o The large intestine includes the cecum, the
colon, the rectum, and the anal canal.
o The large intestine is larger in diameter than
the small intestine (6.5 cm compared with 2.5
cm), but it is shorter in length.
o Functions of the large intestine
▪ The large intestine does not produce
any digestive enzymes, and it does
not absorb any nutrients.
▪ It absorbs water to prevent
dehydration.
▪ It absorbs vitamins (B complex and K)
produced by intestinal flora.
▪ It forms and rids the body of feces through the anus
- Bevrijdt het lichaam van uitwerpselen via de anus

• Disorders of the colon and rectum

o Diarrhea – increased peristalsis and failure to reabsorb water, due to either an
infection or nervous stimulation
o Constipation – feces are dry and hard; condition may be controlled with water and
fiber

68
 o Hemorrhoids – enlarged and inflamed blood vessels of the anus due to chronic
constipation, pregnancy, aging, or anal intercourse
o Diverticulosis – occurrence of pouches of mucosa from weak spots in the muscularis
layer that can become infected; often occur in the descending colon
o Polyps and cancer – small growths found in the epithelial lining that can be benign
(goedaardig) or cancerous

8.6 Nutrition and weight control

• Nutrition
o Obesity
▪ Obesity is defined as abnormal or excessive fat accumulation that presents a
risk to health (WHO).
▪ Crude estimate is BMI (body weight (in kg) /height2 (in cm)).
- BMI (body mass index) > 30 = obese
▪ Risk factors for chronic diseases:
- Diabetes
- Cardiovascular diseases
- Cancer
o Classes of nutrients
▪ Nutrients are components of food that are needed to perform physiological
body functions.
▪ Nutrients include
- Carbohydrates
❖ Carbohydrates are sugars (simple) or polysaccharides
(complex) that are digested into the simple sugars which are
an important energy source.
❖ Grains, beans, tubers, nuts, fruits source for carbohydrates
❖ Can carbohydrates be harmful?
➢ High intake can lead to obesity
➢ A chronically high insulin level may lead to insulin
resistance, type 2 diabetes and increased fat
deposition.
➢ Craving for sweets (sugar dependence)
- Proteins
❖ Proteins are digested into 20 different amino acids which are
used to produce cellular proteins.
❖ Essential amino acids are the 8 amino acids that must be
attained through diet.
❖ Complete proteins that have all essential amino acids are
usually derived from animals such as meat and dairy.
❖ Non-animal sources of proteins are found in legumes, seeds,
nuts.
- Lipids
❖ Essential for every living cell
➢ Cell membrane, steroid hormones
❖ Functions
➢ Mechanical protection
» Cushions, insulation

69
 ➢ Storage for lipophilic vitamins
➢ Source of energy
❖ Saturated fats
➢ Two hydrogen atoms for every carbon atom; Solid at
room temperature
➢ Meat, dairy products, palm kernel oil
➢ Tend to raise LDL (“bad”) cholesterol
❖ Unsaturated fats
➢ Missing one or more pairs of hydrogen atoms;
liquids at room temperature;
➢ Tend to lower LDL (“bad”) cholesterol
➢ Plant sources, olive, safflower, corn, canola oils
➢ Fish (omega-3 fatty acids)
➢ Linked to reduced risk of heart disease
➢ Linoleic acid and linolenic acid are essential fatty
acids (safflower or corn oil)
❖ Can lipids be harmful?
➢ CVD (cardio vascular disease) is often a result of
arteries blocked by plaque made of cholesterol and
saturated fats.
➢ Low density lipoprotein (LDL) is the “bad”
cholesterol because it carries cholesterol from the
liver to the cells.
» HDL (high density lipoprotein) is the “good”
cholesterol removes lipids from tissue
➢ LDL is increased by saturated fats and decreased by
unsaturated fats.
- Minerals
❖ The body contains > 5g of each major mineral and < 5g of
each trace mineral.
➢ Major minerals make up components of cells, body
fluids, and tissues (i.e., calcium).
➢ Minor minerals are components of larger molecules
(i.e., iron in hemoglobin).
❖ A varied and complete diet usually provides necessary
minerals.
- Vitamins
❖ Essential organic compounds needed for metabolism
❖ Vitamins are often enzyme helpers (coenzymes).
❖ There is a total of 13 vitamins in two groups: fat soluble and
water soluble.
❖ Fat-soluble vitamins (see picture)
❖ Water-soluble vitamins (see picture)
➢ Scorbutus, scurvy
» Ascorbic acid essential for collagen
synthesis
» Lethargy, reduced RBC, gum disease, poor
wound healing

70
 ➢ Beriberi:
» Thiamine required for ATP synthesis
» Alcohol abuse (Wernicke–Korsakoff
syndrome)
» Weight loss, emotional disturbances,
impaired sensory perception
➢ B12 deficiency
» Neuropsychiatric symptoms (mania,
psychosis)
» Sensory & motor deficiency, spinal cord
degeneration, seizures, dementia
» Nerve damage

• Eating disorders
o Characterized by abnormal eating habits that damage individual’s health
o Types of eating disorders:
▪ Obesity
▪ Anorexia nervosa: distorted body image & excessive dieting, possibly to the
point of starvation and death

71
 - It is a severe psychological disorder characterized by an irrational
fear of getting fat. Victims refuse to eat enough food to maintain a
healthy body weight.
▪ Bulimia nervosa: binge eating followed by purging (vomiting and/or laxative
use) to avoid gaining weight.
▪ Binge eating disorder: a condition characterized by episodes of overeating
without purging.
- Stress, anxiety, anger, and depression can trigger food binges.
o Often underlying complex emotional issues
o It are also mental disorders (DSM-5): anorexia, bulimia, binge eating

72
9. Respiratory system (hoofdstuk 10 handboek)
9.1 The respiratory system
• The respiratory system
o The organs of the respiratory system ensure that oxygen enters the body and carbon
dioxide leaves the body.
▪ During inspiration, or inhalation (breathing in), air is conducted from the
atmosphere to the lungs by a series of cavities, tubes, and openings.
▪ During expiration, or
exhalation (breathing out),
air is conducted from the
lungs to the atmosphere by
way of the same structures.
o Ventilation is another term for
breathing that includes both
inspiration and expiration.
▪ During ventilation, the
respiratory system depends
on the cardiovascular system
to transport oxygen (O2)
from the lungs to the tissues
and carbon dioxide (CO2)
from the tissues to the lungs.
o Overview of the respiratory system
▪ See picture

9.2 The upper respiratory tract

• The upper respiratory tract
o The nose
▪ The nose opens at the nares (nostrils) that
lead to the nasal cavities.
- The nasal cavities are narrow canals
separated from each other by a
septum composed of bone and
cartilage
▪ Function
- Filters, moistens, warms air
- Smell /odor receptors
❖ They give rise to the sense of smell
o The pharynx (the throat)
▪ It is a funnel shaped passageway that connects the nasal and oral cavities to
the larynx.
- The pharynx has three parts:
❖ The nasopharynx, where the nasal cavities open above the
soft palate
❖ The oropharynx, where the oral cavity opens
❖ The laryngopharynx, which opens into the larynx.

73
 ▪ The tonsils (amandelen) form a protective ring at the junction of the oral
cavity and the pharynx.
- The tonsils, which are composed of lymphoid tissue, are actually
part of the immune system. They contain lymphocytes, which
protect against invasion of inhaled foreign antigens. The tonsils are
the primary defence during breathing, because inhaled air passes
directly over the tonsils. In the tonsils, B cells and T cells respond to
antigens that may subsequently invade internal tissues and fluids.
▪ Functions
- Connection between nasal and oral cavity
- Lymphoid tissue
o The Larynx
▪ It is a cartilaginous structure that serves as
a passageway for air between the pharynx
and the trachea.
▪ The larynx is also called the voice box,
because it houses the vocal cords.
- The vocal cords are mucosal folds supported by elastic ligaments,
and the slit between the vocal cords is called the glottis.
- When air is expelled through the glottis, the vocal cords vibrate,
producing sound.
▪ Ordinarily when food is swallowed, the larynx moves
upward against the epiglottis, a flap of tissue that
prevents food from passing into the larynx.

9.3 The lower respiratory tract

• The lower respiratory tract
o The Trachea (the windpipe)
▪ It is a tube connecting the larynx to the primary bronchi.
▪ Its walls consist of connective tissue and smooth muscle
reinforced by C-shaped cartilaginous rings.
▪ The rings prevent the trachea from collapsing.
o Bronchial tree
▪ Trachea divides into left and right bronchi (which divides
into more branches until it becomes bronchioles), which
lead to the left and right lungs.
- Each bronchiole leads to an elongated space
enclosed by a multitude of air pockets, or sacs,
called alveoli.
o Lungs
▪ The lungs are paired, cone-shaped organs in the thoracic
cavity.
▪ In the center of the thoracic cavity are the trachea, heart,
thymus, and oesophagus.
▪ The lungs are on each side of the trachea.
- The right lung has three lobes, and the left lung
has two lobes, allowing room for the heart, which
points left.

74
 - Each lobe is further divided into lobules, and each lobule has a
bronchiole serving many alveoli (see next).
▪ Each lung is enclosed by pleurae (sing., pleura), two layers of serous
membrane that produce serous fluid.
o The Alveoli
▪ The lungs have about 300 million alveoli, with a total cross-sectional area of
50–70 m2 (size of a tennis court).
▪ Alveoli are surrounded by blood capillaries.
▪ Blood-air barrier: gas exchange occurs between air in the alveoli and blood in
the capillaries.
- Endothelium-simple squamous epithelium.
▪ Lined with surfactant that act as a film of lipoprotein to keep alveoli open.

9.4 Mechanism of breathing

• Mechanism of breathing
o Ventilation of breathing has two phases
▪ 1. Inspiration – an active process of inhalation that
brings air into the lungs
▪ 2. Expiration – a typically passive process of exhalation
that expels air from the lungs
o Ventilation is governed by Boyle’s Law
▪ At a constant temperature, the pressure of a given
quantity of gas is inversely proportional to its volume.

• Inspiration: active phase of ventilation

o The diaphragm and intercostal muscles contract.
o The diaphragm flattens and the rib cage moves upward and
outward.
o Volume of the thoracic cavity and lungs increase.
o The air pressure within the lungs decreases.
o Air flows into the lungs.

• Expiration: passive
o The diaphragm and intercostal muscles relax.
o The diaphragm moves upward and becomes dome-shaped.
o The rib cage moves downward and inward.
o Volume of the thoracic cavity and lungs decreases.
o The air pressure within the lungs increases.
o Air flows out of the lungs.

• Lung volume
o The picture shows the measurements recorded by a spirometer
when a person breathes as directed by a technician.
▪ Tidal volume
- Normally, when we are relaxed, only a small amount of air moves in
and out with each breath, similar perhaps to the tide at the beach.

75
 ▪ Vital capacity
- It is possible to increase the amount of air inhaled and, therefore,
the amount exhaled by deep breathing.
❖ The maximum volume of air that can be moved in plus the
maximum amount that can be moved out during a single
breath is called the vital capacity.
▪ The inspiratory reserve volume
- As noted previously, we can increase inspiration by expanding the
chest and by lowering the diaphragm to the maximum extent
possible.
❖ It is a definite increase over the tidal reserve volume
▪ The expiratory reserve volume
- We can increase expiration by contracting the abdominal and
thoracic muscles.
▪ Residual volume
- The residual volume is the amount of air that can’t be exhaled from
the lungs.

9.5 Control of ventilation

• Nervous control of breathing
o The rhythm of ventilation is controlled by a respiratory
control centre located in the medulla oblongata of the
brain.
▪ The respiratory control centre automatically
sends out nerve signals to the diaphragm and
the external intercostal muscles of the rib cage,
causing inspiration to occur.
▪ When the respiratory centre stops sending
nerve signals to the diaphragm and the rib
cage, the muscles relax and expiration occurs.
o Conscious control resides in the cerebral cortex
▪ Able to modify breath to speak and sing
▪ Able to hold breath temporarily, but can’t
override indefinitely; automatic controls located in medulla oblongata
o Unconscious control by ANS and through chemicals
▪ Medulla oblongata: autonomous nervous control
- Respiratory control center in the brain sends out nerve impulses to
contract muscle for inspiration (see before).

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 - Cardiovascular center regulates the heart rate
- Vasomotor center regulates the blood pressure
- Reflex center for sneezing, vomiting, swallowing, coughing

• Chemical control of breathing

o Two sets of chemoreceptors sense the drop in pH (↑ protons):
▪ Peripherally placed set is located in the aortic and carotid bodies
▪ Centrally placed set (CNS) is located in the medulla oblongata
o ↑ protons (acidosis) ~ increase in CO 2 blood
o ↑ protons (acidosis) >> rate and depth of breathing increases
o ↑ breathing >> more CO 2 removed from blood
o Note, the concentration of oxygen in blood is less monitored

9.6 Gas exchange in the body

• Exchange of gases in the body
o Oxygen and carbon dioxide are exchanged by passive diffusion
o Partial pressure is the amount of pressure each gas exerts (P CO2 or PO2).

• Respiration at 3 levels
o External respiration: gas exchange between air and blood
▪ External respiration: environment-blood
- Exchange of gases between the lung alveoli and the blood capillaries
by passive diffusion.
- PCO2 is higher in the lung capillaries than the air, so CO2 diffuses out
of the capillary to the alveoli.
- The partial pressure pattern for O2 is just the opposite, so O2
diffuses from the alveoli to capillary
▪ Carbon dioxide transport in blood in form of bicarbonate:

▪ Oxygen transport:

o Internal respiration: gas exchange between blood and tissues

▪ The exchange of gases between the blood in the capillaries outside of the
lungs and the tissue fluid/cells.
▪ PO2 is higher in the capillaries than the cells, thus O 2 diffuses out of the blood
into the cells.
▪ Oxyhemoglobin gives up oxygen:

▪ Most CO2 is carried as a bicarbonate ion:

o Cellular respiration: oxygen is used to produce ATP, carbon dioxide as waste.

77
9.7 Respiration and health
• Respiratory problems
o Upper respiratory tract infections
▪ Airborne pathogens, allergens, toxins
▪ Common infections of URT (upper respiratory tract)
- Sinusitis – blockage of sinuses
- Tonsillitis – inflammation of the tonsils
- Laryngitis – infection of the larynx that leads to loss of voice
- Otitis media – infection of the middle ear
o Disorders of the Lower Respiratory System
▪ Lower respiratory tract disorders include infections, restrictive pulmonary
disorders, obstructive pulmonary disorders, and lung cancer.

▪ Tuberculosis
- Mycobacterium tuberculosis, waxy coat provides protection
❖ Infection by inhalation of droplets
❖ Lung scaring
❖ 1/3 world population has latent TB (carrier, not ill, no
transmitter)
❖ World’s top infectious killer (1.5 M deaths in 2013), high risk
for immune-compromised people (HIV)
➢ ‘La dame aux Camelias (Dumas)’, Violetta from ‘La
Traviata’
- Antibiotics for 6-9 months, multidrug-resistant TB
- Oral vaccine
▪ Malignant Mesothelioma:
- Life expectancy: 1-2y after diagnosis
- Mesothelioma: 35-45 y latency
- Banned in 1989 (EPA), 2001 (Belgium)
▪ Cystic fibrosis (mucoviscidosis): gene defect results in thick, sticky mucus
from exocrine glands (lungs, liver, pancreas)
- Genetic mutation
- Belgium 1/20 carrier, ~1200 with CF, 1 baby/week born with CF
- Patient (20y) ~ 2y physical therapy, ~3h/day therapy
- Life expectancy limited: Lung transplantation

78
10. The urinary system (hoofdstuk 11 handboek)
10.1 The urinary system
• The urinary system
o The organ system of the body that
plays a major role in maintaining the
salt, water, and pH homeostasis
of the blood.
o Collectively these organs carry out the
process of excretion, or the removal
of metabolic wastes from the body.
▪ These metabolic waste
materials are the by-products
of the normal activities of the
cells and tissues.

• Functions of the urinary system

o Excretion of metabolic wastes
▪ Mostly water & CO2, but also proteins, …
▪ Mostly of nitrogenous wastes
- Urea is made by the breakdown of amino acids in the liver.
- Uric acid is made by / the final product of the breakdown of
nucleotides.
- Creatinine is made by muscle cells from the breakdown of creatine
phosphate.
o Maintenance of water-salt balance
▪ These are homeostatic mechanisms.
▪ The water-salt balance helps to maintain blood pressure.
o Maintenance of acid-base balance
▪ These are homeostatic mechanisms.
▪ The kidneys excrete hydrogen ions and reabsorb bicarbonate ions.
- This acid-base balance helps maintain a blood pH of 7.4 .
o Hormone secretion: renin and erythropoietin (EPO)
▪ Renin – secreted by the kidneys to allow the adrenal glands to secrete
aldosterone to help regulate water-salt balance
▪ Erythropoietin – secreted by the kidneys to stimulate red blood cell
production when blood oxygen is low
o Reabsorb filtered nutrients and synthesize vitamin D
▪ The urinary system (especially the kidneys) is responsible for reabsorbing
filtered nutrients.
▪ Vitamin D is a molecule/hormone that promotes calcium absorption from
the digestive tract.

• Organs of the urinary system

o Kidneys
▪ Are a pair of organs located one on each side of the vertebral column at the
same level as the small of the lower back.

79
 o Ureters
▪ They conduct urine from the kidneys to the bladder.
▪ The wall of a ureter has three layers
- An inner mucosa (mucous membrane)
- A smooth muscle layer
- An outer fibrous coat of connective tissue.
o Urinary bladder
▪ It stores urine until it is expelled from the
body, sphincters keep it closed.
▪ The bladder has three openings: two for the
ureters and one for the urethra, which drains
the bladder.
▪ The expandable wall contains a middle layer of
circular fibers of smooth muscle and 2 layers of
longitudinal smooth muscle.
▪ Lining of transitional epithelium allows
expansion of mucosa.
▪ Filling activates stretch receptors which signal
to spinal cord.
o Urethra
▪ It is a small tube that extends from the urinary bladder to an external
opening.
▪ Its function is to remove urine from the body

10.2 Structure of the kidney

• Kidneys
o Three regions of the kidney
▪ Renal cortex – an outer
granulated layer
▪ Renal medulla – cone-
shaped tissue masses
called renal pyramids
▪ Renal pelvis – central
cavity that is continuous
with the ureter

• What are nephrons?

o Microscopic functional unit of the
kidney that produces urine
▪ > 1 million per kidney
o Anatomy of a nephron
▪ Glomerulus – a knot of capillaries inside the glomerular capsule where pores
produce a blood filtrate.
▪ Proximal convoluted tubule – epithelial layer with a brush border of
microvilli to allow reabsorption of filtrate components.

80
 ▪ Loop of nephron – U-shaped
structure that has a descending
limb to allow water to leave and
an ascending limb that pushes
out salt.
▪ Distal convoluted tubule – made
of epithelial cells rich in
mitochondria and thus is
important for movement of
molecules from the blood to the
tubule (tubular secretion).
▪ Collecting ducts – several
nephrons share a collecting duct
which serve to carry urine
to the renal pelvis.
o How does the nephron form urine
(see picture)?
▪ When there’s a lot of sugar
(glucose) in your blood
(because of bad absorption)
and therefore also in your
urine, we speak of diabetes.

10.3 Urine formation

• What are the three processes in the
formation of urine?
o Glomerular filtration
▪ It occurs when whole blood
enters the glomerulus by
way of the afferent
arteriole.
▪ Water and small molecules
move from the glomerulus
to the glomerular capsule,
while large molecules and
formed elements remain in
the glomerular blood.
o Tubular reabsorption
▪ It occurs as molecules and
ions are passively and
actively reabsorbed from the
nephron into the blood of
the peritubular capillary
network.
o Tubular secretion
▪ Tubular secretion is a second way to remove substances such as drugs, H+
and creatinine from the blood.

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10.4 Kidneys and homeostasis
• The urinary system and homeostasis
o The kidneys play a major role in homeostasis, from maintaining the water-salt
balance in the body to regulating the pH of the blood.
▪ In doing so, the kidneys interact with every other organ system.

• How do the kidneys maintain homeostasis?

o By excreting wastes
▪ Urea, creatinine, and uric acid
o By maintaining the water-salt balance of blood
▪ Helps regulate the blood volume and pressure
o By maintaining the acid-base balance of blood
▪ Helps regulate the pH-value.
o By giving assistance to other systems
▪ Endocrine, cardiovascular, skeletal, muscular,
nervous, and digestive

• What is the juxtaglomerular apparatus?

o Where the afferent arteriole and the distal convoluted
tubule touch each other.
o It secretes renin, which causes the release of aldosterone
by the adrenal cortex.

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• How is blood volume and pressure maintained by the kidneys?
o Reabsorption of salt – it increases the blood volume.
▪ Aldosterone (mineralocorticoid produced by
adrenal cortex) promotes the excretion of K+
and the reabsorption of Na +.
▪ Atrial natriuretic hormone (ANH) is secreted by
the heart when blood volume increases and
inhibits the secretion of aldosterone which
promotes the excretion of Na +.
o Establishment of solute gradient – a greater
concentration of solute gradient is towards the inner
medulla.
o Reabsorption of water – due to the solute gradient,
water leaves the descending limb of the loop of the
nephron
▪ Then antidiuretic hormone (ADH) from the
pituitary plays a role in water reabsorption at
the collecting duct.
- Alcohol inhibits ADH secretion and thus
increases the amount of urine and dehydration.

• Maintenance of the acid-base balance

o Buffers are a chemical or a combination of chemicals that can take up excess H + or
excess OH-
▪ When H+ are added to blood:
- H+ + HCO3- → H2CO3
▪ When OH- are added to blood:
- OH- + H2CO3 → HCO3- + H2O
o How is the acid-base balance maintained?
▪ The respiratory center in the brain can increase breathing rate if the buffers
cannot maintain the pH-value.
▪ Ultimately, the kidneys are responsible for maintaining blood pH-value.

10.5 Urinary system disorders

• Kidney function disorders
o Diabetes, hypertension, and inherited conditions are the most common cause of
renal (nier) disease and failure such as:
▪ Urethritis – localized infection of the urethra
▪ Cystitis – infection in the bladder

83
 ▪ Pyelonephritis – infection of the kidneys
- Can be very painful; the function of the kidneys is very important, so
when there’s an infection, it can bring other problems with him.
o Kidney stones – hard granules formed in the renal pelvis due to
urinary tract infections (UTIs), enlarged prostate, pH imbalances,
or intake of too much calcium.
o Uremia – high levels of urea and other waste substances in the
blood that cause a serious condition when water and salts are
retained due to extensive nephron damage.

• How can kidney failure be treated?

o Hemodialysis – uses an artificial kidney machine to subtract and add substances to
the blood as needed.
o Continuous ambulatory peritoneal dialysis (CAPD) – uses the peritoneal membrane
to filter the blood and allows a person to go about their normal life without
interruption.
o Kidney replacement – single kidney transplant with a high success rate.

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11. Skeletal system (hoofdstuk 12 handboek)
11.1 Overview of the skeletal system
• Functions of the skeletal system
o The skeleton does more than merely provide a frame for the body. In addition, it has
the following functions:
▪ Supports the body
▪ Protects the soft body parts
▪ Produces blood cells
▪ Stores minerals (calcium and phosphate) and fat
▪ Allows for movement by attaching muscles

• Anatomy of a long bone

o Diaphysis – shaft of the bone made of compact bone
and filled with yellow marrow
▪ Compact bone
- Is composed of osteons with a central
canal containing blood vessels.
- Contains living bone cells called
osteocytes in chambers called lacunae.
o Epiphysis – ends of the bone made mostly of spongy
bone
▪ Spongy bone is made of plates with spaces filled
with red bone marrow.
o Articular cartilage (kraakbeen) – hyaline cartilage found
on the ends of long bones
o Yellow bone marrow – stores fat
o Red bone marrow – makes blood cells, found in spongy
bone and flat bones
o Periosteum – living, outer covering of fibrous
connective tissue
o Ligaments – fibrous connective tissue that connects
bones

• 3 types of cartilage
o Cartilage is flexible connective tissue categorized based
on the type and arrangement of matrix fibers.
o Types
▪ Hyaline cartilage: located at the ends of long bones, nose, ends of ribs,
larynx and trachea
▪ Fibrocartilage: disks between vertebrae and in the knee; stronger than
hyaline cartilage
▪ Elastic cartilage: located in the ear flaps and epiglottis; more flexible than
hyaline cartilage

11.2 Bones of the axial skeleton

• 206 bones of the skeleton
o This pictures represents the axial and the appendicular skeletons.

85
• The axial skeleton, exists of:
o Skull – made of cranium (braincase) and facial bones

▪ The cranium
- Protects the brain.
- Is composed of eight bones (with adults).
- Has some bones that contain the sinuses.
▪ Facial bones, exists of:
- Mandible (bovenkaak)
- Maxillae (onderkaak)
- Zygomatic bones
- Nasal bones
o Hyoid bone
▪ Is the only bone that does not articulate with another bone
o Vertebral column (wervelkolom) – vertebrae and intervertebral
disks
▪ Types of vertebrae
- 33 vertebrae (wervels)

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 ❖ Cervical (7) → nekwervels
▪ Typisch voor zoogdieren, ook voor giraffen, enkel
één soort luipaard
hebben er 9.
❖ Thoracic (12)
❖ Lumbar (5)
❖ Sacrum (5 fused)
❖ Coccyx (4 fused into tailbone)
▪ Intervertebral disks
- Fibrocartilage between vertebrae
o Rib cage – ribs and sternum
▪ Rib(s)
- Protect the heart and lungs
- Is a flattened bone originating from
the thoracic vertebrae
- 12 pairs
❖ 7 pairs true ribs
❖ 3 pairs false ribs
❖ 2 pairs floating ribs
▪ Sternum (known as the breastbone)

11.3 Bones of the appendicular skeleton

• The appendicular skeleton, exists of
o Pectoral girdle and upper limb
▪ Pectoral girdle (gordel)
- Scapula and clavicle
▪ Upper limb
- Arm and hand bones
o Pelvic girdle and lower limb
▪ Pelvic girdle
- Coxal bone (hip bone)
▪ Lower limb
- Leg and foot bones

• Skeletal remains
o Characteristics to be determined
▪ Age is approximated through dentition, studying areas of bone ossification,
and joint condition.
▪ For gender, it is best to use the pelvic bone, but the thickness of long bones
or skull characteristics may also be used.
▪ Ethnicity is difficult to tell, but skull characteristics are most useful.

11.4 Articulations
• Types of joints (gewrichten) = where bones meet bones
o Fibrous – usually immovable such as the sutures (hechtingen) between cranial bones
o Cartilaginous – tend to be slightly movable such as the intervertebral disks
o Synovial – freely movable joints such as the ball-and-socket hip and shoulder joints,
and the hinge knee and elbow joints

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11.5 Bone growth and homeostasis
• What are the important cells in bone growth, remodeling, and repair?
o Osteoblasts – bone-forming cells
o Osteocytes – mature bone cells that maintain bone structure derived from
osteoblasts
o Osteoclasts – bone-absorbing cells
o Chondrocytes – cartilage-forming cells

• Bone development
o Ossification is the process of the formation of the bone in 2 distinct ways:
▪ Intramembranous ossification – bone development between sheets of
fibrous connective tissue → this is used in flat bones
▪ Endochondral ossification – cartilage is replaced by bone
- This is used by most bones

o Types of endochondral ossification

▪ The cartilage model – chondrocytes lay down hyaline cartilage in the shape
of the future bones
▪ The bone collar – osteoblasts secrete bone matrix and results in a collar
made of compact bone
▪ The primary ossification center – osteoblasts are brought interiorly by blood
and lay down spongy bone
▪ The medullary cavity and secondary ossification sites – spongy bone of the
diaphysis is absorbed by osteoclasts becoming the medullary cavity and
secondary ossification centers form in the epiphyses after birth
▪ The epiphyseal (growth) plate – a cartilage band that acts as a growth plate
that allows bones to lengthen

• How do bones lengthen?

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• Hormones affect bone growth
o Vitamin D is converted to a hormone that allows calcium absorption in the intestine
(ingewanden).
o Growth hormone (GH) stimulates general bone growth and the epiphyseal plates.
o Sex hormones increase growth during adolescence (but too much isn’t good either).

• Bone remodeling and homeostasis

o The process of bone renewal, often called bone remodeling, recycles as much as 18%
of bone each year.
▪ Bone remodeling
- Diameter increases as bone
absorption inside the shaft
is matched by bone
formation outside the shaft.
▪ Remodeling allows bones to
respond to stress.
o It regulates the calcium in the blood
through hormones.
▪ Parathyroid hormone (PTH) increases blood calcium by accelerating bone
recycling.
▪ Calcitonin decreases blood calcium.

• Osteoporosis
o It is a condition where bones are weakened due to a decreased bone mass.
o Bone reabsorption exceeds absorption usually by age 40.
o Risk factors include: women, white or Asian, thin, family history, early menopause,
smoking, diet low in calcium, excessive caffeine or alcohol consumption, and a
sedentary lifestyle.
o It can lead to fractures and other complications.
o It can be treated with drugs, hormones, and lifestyle change.

• Steps in bone repair

o Hematoma (6-8 hours) – blood clot
formed between broken bones
o Fibrocartilaginous callus (3 weeks) –
cartilaginous callus forms between
broken bones
o Bony callus (3-4 months) –
cartilaginous callus is turned to bone
o Remodeling – old bone tissue is
replaced by new bone tissue

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12. Muscular system (hoofdstuk 13 handboek)
12.1 Overview of the muscular system
• The muscular system
o Is involved with movement.
▪ This may be the movement of the entire organism (walking or running) or
the movement of materials (blood, food) within the organism.
o It is made up of muscles.
▪ The structure of a muscle allows it to provide movement by contracting, or
shortening.

• Types of muscles
o Humans have three types of muscle tissue: smooth, cardiac, and skeletal.
▪ Smooth – involuntary muscle found in hollow organs and vessels.
▪ Cardiac – involuntary muscle found in the heart.
▪ Skeletal – voluntary muscle that is attached to the skeleton.
o The cells of these tissues are called muscle fibres.

• Skeletal muscles of the body

o Our skeletal muscles are attached to the skeleton, and their contraction causes the
movement of bones at a joint.
o Functions of skeletal muscles
▪ Support the body by allowing us to stay upright.
▪ Allow for movement by attaching to the skeleton.
▪ Help maintain a constant body temperature.
▪ Assist in movement in the cardiovascular and lymphatic vessels.
▪ Protect internal organs and stabilize joints.
o Basic structure of skeletal muscles
▪ A whole muscle contains bundles of skeletal muscle fibres called fascicles.
- Within a fascicle, each fibre is surrounded by connective tissue; the
fascicle is also surrounded by connective tissue.

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 ▪ Muscles are covered with fascia, a type of connective
tissue that extends beyond the muscle and becomes its
tendon.
- Tendon – connective tissue that connects
muscle to bone.
- Small, fluid-filled sacs called bursae (sing.,
bursa) can often be found between tendons
and bones.
❖ The bursae act as cushions, allowing
ease of movement.
o Skeletal muscles work in pairs
▪ The origin (attachment of a muscle on a stationary
bone), and the insertion (attachment of a muscle on a
bone that moves).
- When a muscle contracts, it pulls on the
tendons at its insertion and the bone moves.
▪ Skeletal muscles usually function in groups.
- Consequently, to make a particular movement,
your nervous system does not stimulate a
single muscle.
- Rather, it stimulates an appropriate group of muscles.
▪ For any particular movement, one muscle does most of the work and is
called the agonist, or prime mover.
- A
- While a prime mover is working, other muscles called synergists
function as well. Synergists assist the agonist and make its action
more effective.
o How do skeletal muscles work?
▪ When muscles contract, they shorten.
- Therefore, muscles can only pull; they cannot push.
▪ This means that muscles work in opposite pairs.
- The muscle that acts opposite to a prime mover is called an
antagonist.
▪ Synergists are muscles working in groups for a common action.

12.2 Skeletal muscle fibre concentration

• Muscle fibres and how they slide
o A muscle fibre is a cell containing the usual cellular
components, but special names have been assigned
to some of these components.
▪ The plasma membrane is called the
sarcolemma.
- The sarcolemma encases hundreds
and sometimes even thousands of
myofibrils.
❖ Myofibrils are the contractile
portions of the muscle fibres.

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 ▪ The cytoplasm is called the sarcoplasm.
- The sarcoplasm also contains glycogen, which provides stored
energy for muscle contraction.
- In addition, sarcoplasm includes the red pigment myoglobin, which
binds oxygen until it is needed for muscle contraction.
▪ The SER of a muscle cell is called the sarcoplasmic reticulum and stores
calcium.
o Myofibrils and sarcomeres
▪ Notice that the muscle fibre is roughly cylindrical in shape. Grouped inside
this larger cylinder are smaller cylinders called myofibrils.
- Myofibrils run the entire length of the muscle fibre.
- Myofibrils are composed of even smaller cylinders called
myofilaments, that consists of two types:
❖ Thick myofilaments are made up of a protein called myosin.
❖ Thin myofilaments are composed of a second protein
termed actin.
- Myofibrils are further divided vertically into sarcomeres.
❖ Sarcomeres are the repeating units of actin and myosin
found along a myofibril.
❖ It is made of 2 protein myofilaments (myosin and actin):
➢ Primarily, a thin filament consists of two
intertwining strands of the protein actin.
➢ A thick filament is composed of several hundred
molecules of the protein myosin. Each myosin
molecule is shaped like a golf club.
» These filaments slide over one another
during muscle contraction.
- Thus, the muscle cell is a set of small cylinders (myofilaments)
assembled into larger cylinders (myofibrils) clustered within the
largest cylinder (the muscle fibre).
o The sliding filament model
▪ The movement of actin filaments in relation to myosin filaments is called the
sliding filament model of muscle contraction = the beginning of muscle
contraction
- Nerve impulses travel down a motor neuron to a neuromuscular
junction.
- Acetylcholine (ACh) is released from the neuron and binds to the
muscle fiber.
❖ This binding stimulates the fiber causing calcium to be
released from the sarcoplasmic reticulum.
▪ Muscle contraction continued:
- Released calcium combines with troponin, a molecule associated
with actin.
- This causes the tropomyosin threads around actin to shift and
expose myosin binding sites.
- Myosin heads bind to these sites forming cross-bridges.

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 - ATP binds to the myosin heads and is used for energy to pull the
actin filaments towards the center of the sarcomere – contraction
now occurs.
❖ ATP is needed to attach and detach the myosin heads from
actin.
❖ After death, muscle cells continue to produce ATP through
fermentation and muscle cells can continue to contract.
❖ When ATP runs out, some myosin heads are still attached
and cannot detach, causing rigor mortis.
➢ Rigor mortis and body temperature may be used to
estimate time of death.

• Importance of exercise
o Exercise increases muscle strength, endurance, and flexibility.
o It increases cardiorespiratory endurance.
o HDL (high-density lipoprotein) increases and thus improving cardiovascular health.
o The proportion of protein to fat increases favorably.
o Exercise may prevent certain cancers: colon, breast, cervical, uterine, and ovarian.
o It improves density of bones thus decreasing the likelihood of osteoporosis.
o Exercise enhances mood and may relieve depression.

12.3 Muscular disorders

• Common muscular disorders
o Spasms – sudden, involuntary muscle contractions that are usually painful.
o Convulsions (seizures) – multiple spasms of skeletal muscles.
o Cramps – strong, painful spasms often of the leg and foot.
o Strain – stretching or tearing of a muscle.
o Sprain – twisting of a joint involving muscles, ligaments, tendons, blood vessels, and
nerves.

• Muscular diseases
o These conditions are more serious and always require close medical care.
▪ Myalgia – achy muscles due to injury or infection
▪ Fibromyalgia – chronic achy muscles; not well understood
▪ Muscular dystrophy – group of genetic disorders in which muscles
progressively degenerate and weaken
▪ Myasthenia gravis – autoimmune disorder that attacks the ACh receptor and
weakens muscles of the face, neck, and extremities
▪ Amyotrophic lateral sclerosis (ALS) – commonly known as Lou Gehrig’s
disease; motor neurons degenerate and die leading to loss of voluntary
muscle movement
▪ Sarcomas – cancers that originate in muscle, or the connective tissue
associated with muscle

12.4 Homeostasis
• Both systems produce movement
o Movement is essential to maintaining homeostasis.
o The skeletal and muscular systems work together to enable body movement.

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 ▪ The muscular and skeletal systems work for other types of movements that
are just as important for maintaining homeostasis.

• Both systems protect body parts

o The skeletal system plays an important role by protecting the soft internal organs of
your body.
▪ The brain, heart, lungs, spinal cord, kidneys, and liver and most of the
endocrine glands are shielded by the skeleton.
▪ In particular, the nervous and endocrine organs must be defended, so that
they can carry out activities necessary for homeostasis.

• Muscles help maintain body temperature

o The muscular system helps regulate body temperature.
▪ When you are very cold, smooth muscle constricts inside the blood vessels
supplying the skin.
▪ Thus, the amount of blood close to the surface of the body is reduced. This
helps conserve heat in the body’s core, where vital organs lie.
o Skeletal muscle contraction requires ATP, and using ATP generates heat.

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13. Endocrine system (hoofdstuk 16 handboek)
13.1 Endocrine glands
• Endocrine glands
o The organs of the endocrine
system produce chemical signals
called hormones, which are
involved in the regulation of
other organs.
o The endocrine system works
very closely with the nervous
system to maintain homeostasis.
o Two main types of glands:
exocrine and endocrine.
▪ Exocrine glands — they
secrete their products
into ducts.
▪ Endocrine glands —
they secrete their
products into the
bloodstream, which
delivers them
throughout the body.
- Only target cells can respond to a hormone.
❖ They have receptor proteins for that hormone.
❖ The hormone and the receptor protein bind together like a
key and a lock.

• Comparison of the endocrine an nervous system

o The nervous and endocrine systems both use chemical signals. However, they have
different means of delivering these signals.
▪ The central nervous system (CNS) uses neurotransmitters, and is faster than
the endocrine system.
▪ The endocrine system takes time to deliver hormones, and it takes time for
cells to respond.
- The endocrine system’s effects are slower, but longer lasting.
- Both systems use negative feedback mechanisms.
❖ For example: ff the blood pressure falls, sensory receptors
signal a control centre in the brain. This centre sends out
nerve signals to the arterial walls, so that they constrict, and
blood pressure rises.

• Hormones are chemical signals

o Hormones are a means of communication between cells, between body parts, and
even between individuals.
▪ Most act at a distance from where they are secreted.
▪ They affect the metabolism of cells that have receptors to bind them.

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 o 2 types of hormones
▪ Local hormones affect neighboring cells; they are not carried elsewhere in
the bloodstream.
- That is, prostaglandins.
- That is, growth factors.
▪ Pheromones — they influence the behavior of other individuals.
- Animals rely heavily on pheromones to mark territory and attract a
mate.
- Humans also produce pheromones.

• The action of hormones

o Hormones have a wide range of effects on target cells.
▪ They increase the uptake of
particular substances (such
as glucose).
▪ They alter the target cell’s
structure in some way.
▪ They influence cell
metabolism.
o 2 types of hormones
▪ Peptide hormone—
peptides, proteins,
glycoproteins, and
modified amino acids.
- That is, growth
hormone is a
protein produced and secreted by the anterior pituitary.
- Most hormones are peptide hormones.
❖ Their actions vary depending on the target cell.
❖ That is, when the hormone epinephrine binds to a receptor
on a muscle cell, it breaks glycogen down to glucose for ATP
production.
▪ This occurs in steps: first, cyclic adenosine
monophosphate (cAMP) is formed.
▪ This activates a protein kinase enzyme in the cell,
which activates another enzyme, and so forth.
▪ This is called an enzyme cascade.
- Peptide hormones never enter target cells.
❖ Therefore, the hormone is called the first messenger; cAMP,
which sets the metabolic machinery in motion, is called the
second messenger.
▪ Steroid hormone—derived from cholesterol, so all have the same complex
of four carbon rings.
- Only the adrenal cortex, the ovaries, and the testes produce steroid
hormones.
❖ Thyroid hormones belong to a class of molecules called the
amines, which act in a similar way as steroid hormones.

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 - Steroid hormones do not bind to plasma membrane receptors.
❖ Because they are hydrophobic, they are able to cross the
plasma membrane.
❖ Once inside, it binds to a receptor in the nucleus or
cytoplasm.
- Inside the nucleus, the hormone–receptor complex binds with DNA
and activates certain genes.
❖ Messenger RNA (mRNA) moves to the ribosomes and protein
synthesis follows.
- In general, steroid hormones act more slowly than peptide
hormones, because it takes more time to synthesize new proteins
than to activate enzymes already present in cells.
❖ Their action, however, typically lasts longer.

13.2 Hypothalamus and pituitary gland

• Hypothalamus
o Hypothalamus — link between the nervous and endocrine systems.
▪ Regulates the internal environment via the autonomic nervous system.
- That is, helps control body temperature and water-salt balance.
- That is, also controls the secretions of the pituitary gland.
o Concluded
▪ The pituitary gland is connected to the hypothalamus by a stalk.
▪ The pituitary has two portions: the posterior and anterior pituitary.
- Posterior pituitary
❖ Neurosecretory cells in the hypothalamus produce the
hormones antidiuretic hormone (ADH) and oxytocin.
➢ These hormones pass into the posterior pituitary,
where they are stored.
❖ Certain neurons in the hypothalamus sense the water-salt
balance of the blood.
➢ When blood is too concentrated, ADH is released
from the posterior pituitary.
» ADH causes more water to be reabsorbed
into kidney capillaries.
» As blood becomes dilute, ADH is no longer
released.
 Negative feedback; the effect of the
hormone (to dilute blood) acts to
shut down the release of the
hormone.
❖ Diabetes insipidus—inability to produce ADH.
➢ Produce large amounts of urine, resulting in severe
dehydration and loss of important ions.
➢ Can be corrected with administering ADH.
❖ Oxytocin.
➢ Causes uterine contractions during childbirth and
milk letdown during breastfeeding.

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 » The more the uterus contracts, the more
nerve signals reach the hypothalamus,
causing oxytocin release.
➢ As a baby suckles while being breastfed, nerve
signals from the breasts reach the hypothalamus.
» The hypothalamus now produces oxytocin,
and it is released from the posterior
pituitary.
 Causes the woman’s breast milk to
be released.
➢ The release of oxytocin is controlled by positive
feedback.
» The stimulus continues to bring about an
effect that keeps increases in intensity.
» Positive feedback terminates due to some
external event.
- Anterior pituitary
❖ The hypothalamus controls the anterior pituitary by
producing hypothalamic-releasing and hypothalamic-
inhibiting hormones.
➢ These pass from the hypothalamus to the anterior
pituitary by way of the portal system.
➢ That is, thyroid-releasing hormone (TRH) and
thyroid-inhibiting hormone (TIH).
» TRH stimulates the anterior pituitary to
secrete thyroid-stimulating hormone, and
TIH inhibits it from secreting thyroid-
stimulating hormone.
❖ Thyroid-stimulating hormone (TSH).
➢ Stimulates the thyroid to make thyroid hormones.
❖ Adrenocorticotropic hormone (ACTH).
➢ Stimulates the adrenal cortex to produce cortisol.
❖ Gonadotropic hormones.
➢ Follicle-stimulating hormone (FSH) and luteinizing
hormone (LH) stimulate the gonads (testes and
ovaries) to produce gametes and sex hormones.
❖ Prolactin — produced only after childbirth.
➢ Causes the mammary glands to produce milk.
❖ Melanocyte-stimulating hormone — causes skin color
changes in other animals, but not humans.
❖ Growth hormone (GH), or somatotropic hormone, promotes
skeletal and muscular growth.
➢ Stimulates the rate of protein synthesis.
➢ Stimulates the production of insulin-like growth
factor 1 (IGF-1) by the liver, which also increases
growth and development.
➢ Effects of growth hormone.

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 » Quantities of GH are greatest during
childhood and adolescence.
» Pituitary dwarfism—too little GH in
children.
 Perfect proportions but small
stature.
» Gigantism—too much GH in children.
 Very large stature, and often have
other problems.
» Acromegaly—too much GH in adults.
 Long bone growth is no longer
possible in adults, so only the feet,
hands, and face become overly
large.

13.3 Thyroid and parathyroid glands

• Thyroid gland
o Regulates the metabolic rate of the body, and has a role in calcium homeostasis.
▪ Composed of follicles filled with triiodothyronine (T3), which contains three
iodine atoms, and thyroxine (T4), which contains four.
o If iodine is lacking in the diet, the thyroid cannot produce thyroid hormones.
▪ Low levels of thyroid hormones increases the secretion of TSH.
▪ Endemic goiter—enlarged thyroid from increased levels of TSH.
o Thyroid hormones increase the metabolic rate, but do not have a target organ.
▪ They stimulate all cells of the body to metabolize at a faster rate.
o Congenital hypothyroidism—underdeveloped thyroid at birth; under secretion of
thyroid hormone.
▪ Unless thyroid hormone therapy is begun in the first 2 months of life,
intellectual disability results.
o Myxedema—hypothyroidism in adults.
▪ Symptoms: lethargy, weight gain, loss of hair, slower pulse, lowered body
temperature.
▪ The administration of thyroid hormones restores normal function.
o Exophthalmic goiter—hyperthyroidism (oversecretion of thyroid hormone).
▪ The thyroid is overactive and enlarges, forming a goiter.
▪ Eyes protrude from edema in eye socket tissues.
▪ Symptoms: hyperactivity, nervousness, irritability.
▪ Treatment: surgical removal or destruction of a portion of the thyroid by
radioactive iodine.

• Calcitonin
o Secreted by the thyroid gland when blood calcium levels rise.
▪ Calcium ions have a role in nervous conduction, muscle contraction, and
blood clotting.
▪ Brings about the deposition of calcium into the bones, and reduces the
activity and number of osteoclasts.

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 ▪ When blood calcium levels lower to normal, the release of calcitonin is
inhibited.

• Parathyroid glands
o Parathyroid hormone (PTH) — produced by the parathyroid glands.
▪ Released in response to low blood calcium levels.
▪ Promotes the activity of osteoclasts, which remove calcium from the bones
(increasing blood calcium levels).
▪ Activates vitamin D (calcitriol), which promotes calcium reabsorption by the
kidneys and stimulates absorption of calcium ions from food.
- These effects bring the blood calcium level back to the normal range,
and PTH secretion stops.
o Hypoparathyroidism — insufficient PTH production.
▪ Causes a dramatic drop in blood calcium, followed by excessive nerve
excitability.
- Increased nerve signals cause tetany—continuous muscle
contraction.
▪ Without treatment, causes seizures, heart failure, and death.
o Hyperparathyroidism — over secretion of PTH.
▪ Can result in osteoporosis because of continuous calcium release from the
bones.
▪ May also cause kidney stones.

13.4 Adrenal glands

• Adrenal glands

o Adrenal glands sit atop the kidneys.

▪ Each consists of an inner portion called the adrenal medulla and an outer
adrenal cortex.
- Like the anterior and the posterior pituitary, they are two
functionally distinct endocrine glands.
- The adrenal medulla is under nervous control.
- Parts of the cortex are under the control of corticotropin-releasing
hormone (CRH) from the hypothalamus, and ACTH from the anterior
pituitary.

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• Adrenal medulla
o The hypothalamus sends signals that travel through preganglionic sympathetic nerve
fibers to the adrenal medulla to stimulate it to secrete its hormones.
o Epinephrine (adrenaline) and norepinephrine (noradrenaline)—bring about changes
that occur during a fight-or-flight response, a short-term response to stress.

• Adrenal cortex
o Divided into three regions: zona glomerulosa, zona fasciculata, zona reticularis.
▪ Hormones produced provide a long-term response to stress.
▪ Major types of hormones produced by the adrenal cortex: glucocorticoids,
mineralocorticoids.
- Glucocorticoids
❖ Secretion is controlled by ACTH.
❖ Regulate carbohydrate, protein, and fat metabolism.
❖ Produced in both the zona fasciculata and the zona
reticularis regions.
❖ Cortisol is a glucocorticoid that is active in the stress
response and the repair of damaged tissues.
❖ Glucocorticoids raise the blood glucose level in two ways:
➢ Promote the breakdown of muscle proteins to amino
acids, which are taken up by the liver.
» The liver then converts the amino acids to
glucose.
➢ Promote the metabolism of fatty acids rather than
carbohydrates; this spares glucose.

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 ❖ Cortisone and other glucocorticoids can relieve swelling and
pain from inflammation.
➢ However, by suppressing pain and immunity, they
can also make a person highly susceptible to injury
and infection.
- Mineralocorticoids
❖ Regulate ion balance in the body.
➢ Produced by the zona glomerulosa of the cortex.
➢ Aldosterone is the most important.
» Targets the kidney, where it promotes
absorption of Na+ and excretion of K+.
❖ Renin—secreted by the kidneys when blood Na + levels and
blood pressure are low.
➢ Renin is the enzyme that converts the plasma
protein angiotensinogen to angiotensin I.
➢ Angiotensin I is changed to angiotensin II by a
converting enzyme in lung capillaries.
➢ Angiotensin II stimulates the adrenal cortex to
release aldosterone.
❖ Renin–angiotensin–aldosterone system raises blood
pressure in two ways:
➢ Angiotensin II constricts arterioles.
➢ Aldosterone causes the kidneys to reabsorb Na +.
» This causes water to enter the blood,
increasing blood pressure.
❖ Atrial natriuretic hormone (ANH).
➢ Released by stretched cardiac cells after an increase
in blood volume.
➢ Inhibits the secretion of aldosterone from the
adrenal cortex.
➢ Causes natriuresis, the excretion of sodium ions.
» When sodium ions are excreted, so is water;
therefore, blood pressure lowers to normal.
▪ Also secretes a small amount of male and female sex hormones in both
sexes.
o Sex steroids
▪ In addition to glucocorticoids, the zona fasciculata and zona reticularis
secrete small amounts of sex hormones called gonadocorticoids.
- These include male sex hormones (androgens) and female sex
hormones (estrogen).
❖ The primary androgen is dehydroepiandrosterone (DHEA),
which is a precursor for testosterone, the male sex
hormone.
- In addition, it produces small amounts of estradiol, a form of
estrogen.
- Although in females, most estrogen is produced by the ovaries,
adrenal estradiol does play an important role in regulating growth of
the skeleton in puberty and maintaining bone mass.

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 o Malfunction of the adrenal cortex
▪ Addison disease—hyposecretion of glucocorticoids.
- The presence of excessive but ineffective ACTH causes a bronzing of
the skin (buildup of melanin).
- Without glucocorticoids, glucose cannot be replenished in a stressful
situation.
- Even a mild infection can lead to death.
- In some cases, hyposecretion of aldosterone results in a loss of
sodium and water.
❖ Low blood pressure and severe dehydration can develop as a
result.
▪ Cushing syndrome.
- Over secretion of glucocorticoids.
- Caused by tumors in either the pituitary gland, resulting in excess
ACTH secretion, or the adrenal cortex itself.
- The most common cause is taking glucocorticoids
to treat other conditions (that is, to suppress chronic inflammation).
- Excess glucocorticoids cause muscle protein to be broken down and
fat to be deposited in the midsection.
- Excess production of adrenal male sex hormones
in women may result in masculinization.
❖ That is, increase in body hair, deepening of the voice, and
beard growth.
- Treatment: a reduction in the amount of cortisone being taken,
cortisol-inhibiting drugs, or surgery to remove the tumor.

13.5 Pancreas
• Pancreas
o Located behind the stomach, near the duodenum.
▪ Both exocrine and endocrine.
- Exocrine tissue secretes digestive enzymes.
- Endocrine tissue is called pancreatic islets (islets of Langerhans) that
contain a variety of cell types:
❖ A cells—secrete glucagon.
❖ B cells—secrete insulin.
❖ D cells—secrete somatostatin.
➢ Regulate the digestive processes.
o Insulin
▪ Unlike most other endocrine organs, the pancreas is not under pituitary
control.
- It responds directly to changes in blood glucose levels.
▪ It is secreted when blood glucose levels are high (after eating).
▪ It stimulates the uptake of glucose by cells, especially liver cells, muscle cells,
and adipose cells.
- In these ways, insulin lowers blood glucose levels.
o Glucagon
▪ It is secreted when blood glucose levels are low (between meals).
▪ It stimulates the liver to break down glycogen to glucose.

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 ▪ Also promotes the use of fat and protein in preference to glucose as energy
sources.
▪ Adipose cells break down fat to glycerol and fatty acids.
- The liver takes these up and uses them to make glucose.
- In these ways, glucagon raises the blood glucose level.

• Diabetes mellitus
o = An excess of glucose in the blood.
o As blood glucose levels rise, glucose, along with water, is excreted in the urine.
▪ Diabetics urinate frequently and are always thirsty.
o Other symptoms: fatigue, constant hunger, and weight loss.
o The high blood glucose levels often cause an increase in blood pressure due to
osmosis.
▪ Can damage the small capillaries of the kidneys, eyes.
o Diabetics often experience vision problems due to diabetic retinopathy and swelling
in the lens.
o If untreated, often develop serious and even fatal complications.
▪ Sores that don’t heal develop into severe infections.
▪ Blood vessel damage causes kidney failure, nerve destruction, heart attack,
or stroke.
o Types of diabetes
▪ Two types of diabetes: Type 1 and Type 2.
- Type 1 is sometimes called juvenile diabetes or insulin-dependent
diabetes mellitus (IDDM).
❖ The pancreas does not produce enough insulin.
❖ Caused by exposure to an environmental agent, most likely a
virus.
❖ Autoimmune response destroys the pancreatic islets.
❖ The body metabolizes fat, which leads to the buildup of
ketones in the blood, called ketoacidosis.
➢ Increases acidity of the blood; can lead to coma,
death.
❖ Type 1 diabetics must inject insulin daily.
❖ Blood sugar level may swing between hypoglycemia (low
blood glucose) and hyperglycemia (high blood glucose).
➢ Symptoms of both: perspiration, pale skin, shallow
breathing, and anxiety.
➢ If the problem is hypoglycemia, the treatment is
ingesting sugar.
➢ If the problem is hyperglycemia, the treatment is
insulin.
- Type 2 is also known as adult-onset diabetes, or non-insulin-
dependent diabetes mellitus (NIDDM).
❖ Most adult diabetics have type 2 diabetes.
❖ Patient is often overweight or obese; adipose tissue
produces a substance that impairs insulin receptor function.
❖ Occurs more often in certain families or even ethnic groups.

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 ➢ That is, 77% more common in African Americans
than in non-Hispanic whites.
❖ Cells are insulin resistant.
❖ Can prevent or at least control type 2 diabetes by adhering
to a special diet and exercising regularly.
➢ If this fails, oral drugs can help.
❖ Millions of Americans may have type 2 diabetes without
knowing.
❖ The effects of untreated type 2 diabetes are as serious as
those of type 1.
▪ Although the causes of these forms of diabetes are different, they can occur
in children or adults.
o Testing for diabetes
▪ Oral glucose tolerance test for diabetes.
- After the patient ingests glucose, blood glucose concentration is
measured at intervals.
- In a diabetic, blood glucose levels rise greatly and remain elevated
for several hours, and glucose appears in the urine.
- In a nondiabetic person, the blood glucose level rises somewhat and
then returns to normal after about 2 hours.

13.6 Other endocrine glands

• Other endocrine glands
o Gonads – the male testes and female ovaries.
▪ Produce hormones and therefore are considered endocrine glands.
▪ In addition, the thymus and pineal gland, as well as some other tissues in the
body, have endocrine functions.
o The testes and ovaries are controlled by the hypothalamus and pituitary.
▪ The testes are located in the scrotum, and the ovaries are located in the
pelvic cavity.
- The testes produce androgens (male sex hormones), such as
testosterone.
- The ovaries produce estrogen and progesterone (female sex
hormones)
▪ Testosterone, estrogen, and progesterone feed back to control the
hypothalamic secretion of gonadotropin-releasing hormone (GnRH).
▪ The pituitary gland secretion of follicle-stimulating hormone (FSH) and
luteinizing hormone (LH), the gonadotropic hormones, is also controlled by
feedback from the sex hormones.
▪ Because of gonadotropic hormones, the testes begin to release increased
amounts of testosterone starting at puberty.
- Testosterone stimulates the growth of the penis and the testes.
❖ It also brings about male secondary sex characteristics:
➢ Facial, axillary (underarm), and pubic hair.
➢ The larynx and vocal cords enlarge (deeper voice).
➢ Stimulates oil and sweat glands (acne, body odor).
➢ Can cause baldness.

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 ▪ Anabolic steroids—made of testosterone Effects of estrogen and
progesterone.
- Estrogen secreted at puberty stimulates the growth of the uterus
and the vagina.
- Estrogen is necessary for egg maturation.
- Female secondary sex characteristics:
❖ Body hair and fat distribution, more fat under the skin.
❖ The pelvic girdle is wider, breasts.
❖ Monthly menstruation.
o Thymus—beneath the sternum.
▪ Reaches its largest size and is most active during childhood.
- With aging, the organ gets smaller and becomes fatty.
▪ Thymosins —cause lymphocytes to mature.
- As lymphocytes from the bone marrow pass through the thymus,
they are transformed into T lymphocytes.
o Pineal gland—in the brain.
▪ Produces melatonin, primarily at night.
- Regulates daily sleep–wake cycle.
❖ We get sleepy at night when melatonin levels increase and
awaken once daylight returns and melatonin levels are low.
❖ Circadian rhythms—daily 24-hour cycles; controlled by the
hypothalamus.
- Also regulates sexual development.

• Hormones from other organs or tissues.

o Erythropoietin (EPO)—secreted by the kidneys in response to a low oxygen blood
level.
▪ Stimulates red blood cell formation in the red bone marrow.
o Many organs and cells produce peptide growth factors, which stimulate cell division.
▪ Some are released into the blood; others diffuse to nearby cells.
o Leptin—produced by adipose tissue.
▪ Acts on the hypothalamus; it signals satiety (fullness).
▪ Obese people may have plenty, but it may be defective or they may not have
enough receptors.
o Prostaglandins—made from arachidonate, a fatty acid.
▪ Not distributed in the blood; they act locally.
▪ Are produced by damaged tissues; cause pain.
▪ In the uterus, cause muscles to contract (cramps).
▪ Help cause fevers.
▪ Reduce gastric secretion, so treat gastric reflux.
▪ Lower blood pressure, so treat hypertension.
▪ Inhibit platelet aggregation, so prevent thrombosis.

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14. Reproductive system (handboek hoofdstuk 17)
14.1 Human life cycle
• The reproductive system
o Quite different in males and females.
▪ In both males and females, the
reproductive system is responsible for the
production of gametes, the cells that
combine to form a new individual of the
species.
▪ In females, the reproductive system has the
added function of protecting and
nourishing the developing foetus until
birth.
o The reproductive organs, or genitals, have the
following functions:
▪ Males produce sperm within testes, and
females produce eggs within ovaries.
▪ Males nurture and transport the sperm in
ducts until they exit the penis. Females
transport the eggs in uterine tubes to the
uterus.
▪ The male penis functions to deliver sperm
to the female vagina, which receives the sperm. The vagina also transports
menstrual fluid to the exterior and acts as the birth canal.
▪ The uterus of the female allows the fertilized egg to develop within her body.
After birth, the female breast provides nourishment in the form of milk.
▪ The testes and ovaries produce the sex hormones. The sex hormones have a
profound effect on the body, because they bring about masculinization or
feminization of various features. In females, the sex hormones also allow a
pregnancy to continue.
o Unlike animals, the reproductive system of humans does not begin to fully function
until puberty is complete.
▪ At the completion of puberty, the individual is capable of producing children.

• Mitosis and meiosis

o During the majority of our life cycle, our cells divide by a process called mitosis.
▪ Mitosis is duplication division, meaning that each of the cells that exit mitosis
has the same complement of 46 chromosomes.
- In other words, when a cell divides, it produces exact copies of itself
by mitosis.
▪ Mitosis is the type of cell division that plays an important role during growth
and repair of tissues.
o For the purposes of reproduction, special cells in the body undergo a type of cell
division called meiosis.
▪ Meiosis takes place only in the testes of males during the production of
sperm and in the ovaries of females during the production of eggs.

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 ▪ It has two functions (see further, chapter 19), the first of which is called
reduction division.
- During meiosis, the chromosome number is reduced from the
normal 46 chromosomes, called the diploid or 2n number, down to
23 chromosomes, called the haploid or n number of chromosomes.
- This process requires two successive divisions, called meiosis I and
meiosis II, and is involved in the formation of gametes, or sex cells.
▪ Meiosis also introduces genetic variation, thus ensuring that the new
individual is not an exact copy of either parent.
o The fusing of the egg and sperm form a cell called the zygote.
▪ Because a sperm has 23 chromosomes and the egg has 23 chromosomes, the
zygote has 46 chromosomes altogether.
▪ Without meiosis, the chromosome number in each generation of humans
would double, and the cells would no longer be able to function.

14.2 Male reproductive system

• The male reproductive system

o The male gonads, or primary sex organs, are paired testes (sing., testis), suspended
within the sacs of the scrotum.
o Sperm produced by the testes mature within the epididymis (pl., epididymides), a
tightly coiled duct lying just outside each testis.
▪ Maturation seems to be required for sperm to swim to the egg.
o When sperm leave an epididymis, they enter a vas deferens (pl., vasa deferentia),
also called the ductus deferens.
▪ The sperm may be stored for a time in the vas deferens.
▪ Each vas deferens passes into the abdominal cavity, where it curves around
the bladder and empties into an ejaculatory duct.
- The ejaculatory ducts enter the urethra.
o At the time of ejaculation, sperm leave the penis in a fluid called semen.
o A pair of seminal vesicles lie at the base of the bladder, and each has a duct that
joins with a vas deferens.
o The prostate gland is a single, doughnut-shaped gland that surrounds the upper
portion of the urethra just below the bladder.

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 o Bulbourethral glands (also called Cowper's glands) are pea-sized organs that lie
posterior to the prostate on either side of the urethra.
▪ Their secretion makes the seminal fluid gelatinous.

• The penis and male orgasm

o The penis is the male organ of sexual intercourse.
▪ It also contains the urethra of the urinary system.
▪ The penis has a long shaft and an enlarged tip called the glans penis.
▪ The layer of skin covering the glans penis is called the foreskin.
▪ Spongy, erectile tissue containing distensible blood spaces extends through
the shaft of the penis.
▪ During sexual arousal, autonomic nerves release nitric oxide (NO).
- This stimulus leads to the production of cGMP (cyclic guanosine
monophosphate), a high-energy compound similar to ATP.
❖ The cGMP causes the smooth muscle of incoming arterial
walls to relax and the erectile tissue to fill with blood.
❖ The veins that take blood away from the penis are
compressed, and the penis becomes erect.
▪ Erectile dysfunction (ED) or impotency is the inability to achieve or maintain
an erection suitable for sexual intercourse.
▪ As sexual stimulation intensifies, sperm enter the urethra from each vas
deferens, and the glands contribute secretions to the seminal fluid.
- Once seminal fluid is in the urethra, rhythmic muscle contractions
cause it to be expelled from the penis in spurts (ejaculation).
▪ The psychological sensation of pleasure is centred in the brain.
- However, the physiological reactions involve the reproductive organs
and associated muscles, as well as the entire body.

• Male gonads: the testes

o The testes, which produce sperm as well as the male sex hormones, lie outside the
abdominal cavity of the male, within the scrotum.
o Sperm production
▪ Sperm are produced within the seminiferous tubules of the testes.
▪ Sertoli cells help nourish sperm and regulate the process of sperm
production (spermatogenesis).
o Sperm anatomy: three parts

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 ▪ The head is covered by a cap called the acrosome which stores enzymes
needed to penetrate the egg.
▪ The middle piece contains mitochondria to make ATP.
▪ The tail provides movement for the sperm.

• Hormonal regulation in males

o Gonadotropin-releasing hormone (GnRH) – secreted by the thalamus to control the
release of other hormones
▪ Two gonadotropic hormones
- Follicle-stimulating hormone (FSH) – promotes the production of
sperm
- Luteinizing hormone (LH) – controls the production of testosterone
o Testosterone is important for normal development and functioning of the male
reproductive organs.
▪ Testosterone also brings about and maintains the male secondary sex
characteristics that develop at the time of puberty.
▪ Testosterone causes males to develop noticeable hair on the face, the chest,
and occasionally other regions of the body, such as the back.
▪ Testosterone is responsible for the greater muscular development in males.

14.3 Female reproductive system

• The female reproductive system

o The female gonads are paired ovaries that lie in shallow depressions, one on each
side of the upper pelvic cavity.
▪ The ovaries produce eggs, also called ova (sing., ovum), and the female sex
hormones oestrogen and progesterone.

• The genital tract

o The uterine tubes, also called the oviducts or fallopian tubes, extend from the uterus
to the ovaries. However, the uterine tubes are not attached to the ovaries.
▪ Instead, they have finger like projections called fimbriae (sing., fimbria) that
sweep over the ovaries.

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 o When an egg (ovum) bursts from an ovary during ovulation, it is usually swept into a
uterine tube by the combined action of the fimbriae and the beating of cilia that line
the uterine tube.
▪ Once in the uterine tube, the egg is propelled slowly by ciliary movement
and tubular muscle contraction toward the uterus.
o Fertilization, and therefore zygote formation, usually takes place in the uterine tube.
▪ A developing embryo normally arrives at the uterus after several days, and
then implantation occurs.
o The uterus is a thick-walled, muscular organ about the size and shape of an inverted
pear.
▪ The uterine tubes join the uterus at its upper end. At its lower end, the cervix
enters the vagina nearly at a right angle.
o Development of the embryo and foetus normally takes place in the uterus.
▪ The lining of the uterus, called the endometrium, participates in the
formation of the placenta.
- The endometrium supplies nutrients needed for embryonic and
foetal development.
- The endometrium has two layers:
❖ A functional layer that is shed during each menstrual period.
➢ In the nonpregnant female, the functional layer of
the endometrium varies in thickness according to a
monthly reproductive cycle called the uterine cycle.
❖ A basal layer of reproducing cells.

• External genitals
o The external genital organs of the female are
known collectively as the vulva.
▪ The vulva includes two large, hair-
covered folds of skin called the labia
majora.
- The labia minora are two small
folds lying just inside the labia
majora.
o The glans clitoris is the organ of sexual arousal in
females.
▪ Like the penis, contains a shaft of erectile tissue that becomes engorged with
blood during sexual stimulation.
o The urinary and reproductive systems in the female are entirely separate.

• Orgasm in females
o Orgasm occurs at the height of the sexual response.
▪ Blood pressure and pulse rate rise, breathing quickens, and the walls of the
uterus and uterine tubes contract rhythmically.
o A sensation of intense pleasure is followed by relaxation when organs return to their
normal size.
o Females have no refractory period, and multiple orgasms can occur during a single
sexual experience.

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14.4 The ovarian cycle
• The ovary
o An ovary contains many
follicles, each containing
an immature egg (oocyte).
▪ A female is born
with over 2
million, but at
puberty a female
has 300,000-
400,000 follicles.
▪ During the lifetime
of a female only
400 follicles
mature, because a
female usually
produces only one egg per month during her reproductive years.
- It matures until menopause (= the end of ovarian and uterine
cycles).
▪ As the follicle matures during the ovarian cycle, it changes from a primary to
a secondary to a vesicular (Graafian) follicle.
o Ovulation is the monthly release of an oocyte from the ovary when a follicle
ruptures.
o Phases of the ovarian cycle
▪ During the first half, or follicular phase, FSH promotes the development of
follicles that primarily secrete oestrogen.
▪ Next, the luteal phase begins. During the luteal phase of the ovarian cycle, LH
promotes the development of the corpus luteum.
- The corpus luteum secretes high levels of progesterone and some
oestrogen.
o Oestrogen and progesterone
▪ Oestrogen and progesterone affect not only the uterus but other parts of the
body as well.
- Oestrogen is largely responsible for the secondary sex characteristics
in females, including body hair and fat distribution.
- Both oestrogen and progesterone are also required for breast
development.
❖ Other hormones are involved in milk production (prolactin)
following pregnancy and milk let down (oxytocin) when a
baby begins to nurse.
▪ Menopause, the period in a woman’s life during which the ovarian cycle
ceases, is likely to occur between ages 45 and 55.
- The ovaries are no longer responsive to the gonadotropic hormones
produced by the anterior pituitary, and the ovaries no longer secrete
oestrogen or progesterone.

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• Uterine cycle: nonpregnant
o The female sex hormones, oestrogen
and progesterone, have numerous
functions.
▪ One function of these
hormones affects the
endometrium, causing the
uterus to undergo a cyclical
series of events known as the uterine cycle.
▪ 28 day cycles are divided as follows (see picture).

• Fertilization and pregnancy

o Only one sperm is needed to fertilize the egg, which is then called a zygote.
▪ Development begins even as the zygote travels down the uterine tube to the
uterus.
▪ The endometrium is now prepared to receive the developing embryo.
o The placenta, which sustains the developing embryo and later the foetus, originates
from both maternal and foetal tissues.
▪ It is the region of exchange of molecules between foetal and maternal blood,
although the two rarely mix.
▪ At first, the placenta produces human chorionic gonadotropin (HCG), which
maintains the corpus luteum in the ovary.
▪ Eventually, the placenta produces progesterone and some oestrogen. The
corpus luteum is no longer needed and it regresses.

14.5 Control of reproduction

• Birth control methods
o They are used to regulate the number of children an individual or a couple has.
▪ The most reliable method of birth control is abstinence—not engaging in
sexual intercourse.
- This form of birth control has the added advantage of preventing
transmission of sexually transmitted diseases.
▪ The withdrawal method is one of the least effective methods of
contraception, with an effectiveness of 75%.
o Contraceptives are medications and devices that reduce the chance of pregnancy.
▪ Oral contraception, known as birth control pills, is the most effective form of
contraception.
- These pills contain a combination of oestrogen and progesterone.
- Most birth control pills are taken daily.
❖ For the first 21 days, the pills contain active hormones. This
is followed by 7 days of inactive pills.
- The oestrogen and progesterone in the birth control pill or a patch
applied to the skin effectively shuts down the pituitary production of
both FSH and LH.
❖ Follicle development in the ovary is prevented. Because
ovulation does not occur, pregnancy cannot take place.
o An intrauterine device (IUD) is a small piece of moulded plastic, and sometimes
copper, that is inserted into the uterus by a physician.

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 ▪ IUDs alter the environment of the uterus and uterine tubes to reduce the
possibility of fertilization.
▪ If fertilization should occur, implantation cannot take place.
o The diaphragm is a soft latex cup with a flexible rim that lodges behind the pubic
bone and fits over the cervix.
▪ The diaphragm can be inserted into the vagina no more than 2 hours before
sexual relations.
▪ It must be used with spermicidal jelly or cream and should be left in place at
least 6 hours after sexual relations.
o The male and female condoms offer some protection against sexually transmitted
diseases in addition to helping prevent pregnancy.
▪ Female condoms consist of a large polyurethane tube with a flexible ring that
fits onto the cervix.
▪ A male condom is most often a latex sheath that fits over the erect penis.
- The ejaculate is trapped inside the sheath and thus does not enter
the vagina.
o For individuals who are experiencing infertility, or an inability to achieve pregnancy,
a number of assisted reproductive technologies may be used to increase the chances
of conceiving a child.

• Emergency contraception
o Emergency contraception, or “morning-after pills,” consists of medications that can
prevent pregnancy after unprotected intercourse.
▪ Some treatments can be started up to 5 days after unprotected intercourse.
o Types of emergency contraception
▪ Preven, a morning-after pill, upsets the normal uterine cycle so an embryo
has a hard time implanting (85% effective).
▪ RU-486 (mifepristone) causes loss of an implanted embryo (95% effective).

• Surgical methods
o Vasectomy and tubal ligation are two methods used to bring about sterility, the
inability to reproduce.
▪ Vasectomy consists of cutting and sealing the vas deferens from each testis
so that the sperm are unable to reach the seminal fluid ejected at the time of
orgasm.
▪ Tubal ligation consists of cutting
and sealing the uterine tubes.
- Pregnancy rarely occurs,
because the passage of the
egg through the uterine
tubes has been blocked.
o It is best to view a vasectomy or tubal
ligation as permanent.

• Infertility
o Infertility is the failure of a couple to achieve pregnancy after 1 year of regular,
unprotected intercourse.
o The cause of infertility can be evenly attributed to the male and female partners.

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 ▪ The most frequent cause of infertility in males is low sperm count and/or a
large proportion of abnormal sperm, which can be due to environmental
influences.
- It appears that a sedentary lifestyle coupled with smoking and
alcohol consumption is most often the cause of male infertility.
▪ Body weight appears to be the most significant factor in causing female
infertility.
- In overweight women, leptin levels are higher, which impacts GnRH
and FSH.
- The ovaries of many overweight women contain many small follicles
that fail to ovulate.
▪ Other causes of infertility in females are blocked uterine tubes due to pelvic
inflammatory disease and endometriosis.
- Endometriosis is the presence of uterine tissue outside the uterus,
particularly in the uterine tubes and on the abdominal organs.
❖ The cells go through the usual uterine cycle, causing pain and
structural abnormalities that make it more difficult for a
woman to conceive.
o Assisted reproductive technologies
▪ It consists of techniques used to increase the chances of pregnancy.
▪ Often, sperm and/or eggs are retrieved from the testes and ovaries, and
fertilization takes place in a clinical or laboratory setting.
- Artificial Insemination by Donor (AID)
❖ Sperm are placed in the vagina by a physician. Sometimes a
woman is artificially inseminated by her partner’s sperm.
➢ This is especially helpful if the partner has a low
sperm count, because the sperm can be collected
over time and concentrated, so that the sperm count
is sufficient to result in fertilization.
❖ Often, however, a woman is inseminated by sperm acquired
from a donor who is a complete stranger to her.
❖ At times, a combination of partner and donor sperm is used.
- In Vitro Fertilization (IVF)
❖ Conception occurs in laboratory glassware.
❖ Ultrasound machines can now spot follicles in the ovaries
that hold immature eggs.
➢ The immature eggs are then brought to maturity in
glassware, and then concentrated sperm are added.
➢ After about 2 to 4 days, the embryos are ready to be
transferred to the uterus of the woman, who is now
in the secretory phase of her uterine cycle.
- Gamete intrafallopian transfer (GIFT)
❖ Similar to IVF, except the eggs and sperm are placed in the
oviducts immediately after they have been brought together
- Surrogate mothers
❖ Women are legally paid to have babies
- Intracytoplasmic sperm injection (ICSI)

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 ❖ A single sperm is injected into an egg, typically when a man
has infertility problems.
o Another option is adoption
▪ Then you get the legal custody of a nonbiological child.

14.6 Sexually transmitted diseases

• Sexually transmitted diseases are caused by viruses, bacteria, fungi, and parasites.
o STD’s caused by viruses
▪ They cannot be treated with antibiotics, but there are some antivirals.
- HIV
- Genital warts
- Genital herpes
- Hepatitis
o STD’s caused by bacteria
▪ They can be treated with antibiotics.
- Chlamydia
- Gonorrhea
- Syphilis

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 15. Development and aging (hoofdstuk 18 handboek)
15.1 Fertilization
• Fertilization
o This is the union of a sperm and an egg to form a zygote, the first cell of that new
individual.
o Steps of fertilization
▪ Sperm makes its way through the corona radiata.
- A few layers of adhering follicular cells are collectively called the
corona radiata.
▪ Acrosomal enzymes digest a portion of zona pellucida.
- Zona pellucida = an extra cellular matrix
▪ Sperm binds to and fuses with oocyte plasma membrane.
▪ Sperm nucleus enters cytoplasm of oocyte.
▪ Cortical granules release enzymes. Zona pellucida become fertilization
membrane.
▪ Sperm and egg pronuclei are enclosed in a nuclear envelope.

15.2 Pre-embryonic and embryonic development

Human development proceeds from pre-embryonic to embryonic development and then through
foetal development.

• Processes of development
o Cleavage – cells undergo division without the embryo increasing in size.
o Growth – cells undergo division as well as increase in size.
o Morphogenesis – the embryo begins to take shape as cells migrate.
o Differentiation – when cells take on specific structure and function (the nervous
system is the first visible system).

• Stages of development
o Pre-embryonic development encompasses the events of the first week after
fertilization.
▪ Immediately after fertilization, the zygote divides repeatedly as it passes
down the uterine tube to the uterus (= cleavage).
▪ A morula is a compact ball of embryonic cells that becomes a blastocyst.
- The many cells of the blastocyst arrange themselves so that there is
an inner cell mass surrounded by an outer layer of cells.
❖ The inner cell mass will become the embryo, and the layer of
cells will become the chorion.
➢ The early appearance of the chorion emphasizes the
complete dependence of the developing embryo on
this extraembryonic membrane (see further).
o The extraembryonic membranes are not part of the embryo and foetus.
▪ Instead, as implied by their name, they are outside the embryo.
▪ Different types of the extraembryonic membranes and their function
- Chorion – fetal half of the placenta, the organ that provides the
embryo with nourishment and gets rid of wastes.

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 - Allantois – gives rise to the bladder and the blood
vessels of the umbilical cord that carry blood to
and from the fetus.
- Yolk sac – contains many blood vessels and where
blood cells first form (there is little yolk in
humans).
- Amnion – contains amniotic fluid that cushions
and protects the embryo.
o Embryonic development begins with the second week after
fertilization and lasts until the end of the second month.
▪ In the second week
- Pregnancy begins after implantation.
- Human chorionic gonadotropin (HCG) is secreted, maintaining the
corpus luteum and the endometrium.
❖ HCG is the basis for a pregnancy test.
- The inner cell mass detaches itself and becomes the embryonic disk
that will go through gastrulation to become three primary germ
layers (ectoderm, mesoderm, and endoderm).
▪ In the third week
- Nervous system begins to develop.
- The posterior neural tube will become the spinal cord and brain.
- Development of the heart begins.
▪ In the fourth and fifth weeks
- During the fourth week, the embryo is barely larger than the height
of this print.
❖ A body stalk (future umbilical
cord) connects the embryo to
the chorion, which has treelike
projections called chorionic
villi.
❖ Once this process is complete,
the umbilical cord is fully
formed.
➢ The umbilical cord
connects the
developing embryo to
the placenta.
❖ Soon, limb buds appear.
➢ Later, the arms and legs develop from the limb buds,
and even the hands and feet become apparent
- During the fifth week, the head enlarges and the sense organs
become more prominent.
❖ It is possible to make out the developing eyes and ears, and
even the nose.
▪ Six through eight weeks
- During the sixth through eighth weeks of development, the embryo
changes to form an easily recognized as a human.

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 - The nervous system is developed well enough to permit reflex
actions, such as a startle response to touch.

15.3 Foetal development

• Foetal development
o The placenta is the source of progesterone and oestrogen during pregnancy.
▪ These hormones have two functions
- Because of negative feedback on the hypothalamus and anterior
pituitary, they prevent any new follicles from maturing.
- They maintain the endometrium.
❖ Menstruation does not usually occur during pregnancy.
▪ The placenta has a foetal side contributed by the chorion and a maternal
side consisting of uterine tissue.
o Foetal circulation
▪ The umbilical cord stretches between the placenta and the foetus.

• Events of foetal development

o Foetal development includes the third through the ninth months of development.
▪ At this time the foetus is recognizably human, but many refinements still
need to be added.
▪ The foetus usually increases in size and gains the weight it needs to live as an
independent individual.
o Third and fourth months
▪ At the beginning of the third month, the foetal head is still very large relative
to the rest of the body.
- Head growth begins to slow down as the rest of the body increases
in length.
▪ Fingernails, nipples, eyelashes, eyebrows, and hair on the head appear.
▪ Cartilage begins to be replaced by bone as ossification centres appear in
most of the bones.
- Cartilage remains at the ends of the long bones, and ossification is
not complete until age 18 or 20 years.
▪ The skull has six large, membranous areas called fontanels.
- These permit a certain amount of flexibility as the head passes
through the birth canal and they allow rapid growth of the brain
during infancy.
❖ Progressive fusion of the skull bones causes the fontanels to
close, usually by 2 years of age.
▪ During the fourth month, the foetal heartbeat is loud enough to be heard
when a physician applies a stethoscope to the mother’s abdomen.
o Fifth through seventh months
▪ Fetal movement can be felt by the mother.
▪ Fetus is in fetal position, with the head bent down and in contact with the
flexed knees.
▪ Eyelids are fully open.
▪ Fetus size has increased to 300mm and 1380g.

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 o Eighth through ninth months
▪ At the end of 9 months, the foetus is about 530 mm long and weighs about
3,400 g.
- Weight gain is due largely to an accumulation of fat beneath the
skin.
▪ As the end of development approaches, the foetus usually rotates, so that
the head is pointed toward the cervix.

• Preventing birth defects

o Get physical exams by a trained doctor.
o Have good health habits: proper nutrition and adequate sleep and exercise.
o Avoid smoking, alcohol, and drug abuse.
o Avoid having X-rays.
o Avoid certain medications and supplements.
o Avoid sexually transmitted diseases or know if you have one.

• Development of the sex organs

o Sex of an individual is determined at conception (XX is female and XY is male).
o If the SRY (the sex-determining region on the Y chromosome) gene is present at
week 6 then the embryo develops into a male.
▪ Anti-Mϋllerian hormone secreted by the testes prevents the development of
female sex organs.
o Abnormal development of the sex organs
▪ XY female syndrome - an individual develops into a female because a piece
of the Y chromosome containing the SRY gene is missing.
▪ XX male syndrome – an individual develops into a male because the same
small piece of the Y containing the SRY gene is present on an X chromosome.
o Ambiguous sex determination
▪ Results from the absence of testosterone, anti-Mϋllerian hormone and/or
DHT (= Dihydrotestosterone, it directs the development of the urethra,
prostate gland, penis and scrotum).
- Androgen insensitivity syndrome – all hormones are made, but
testosterone receptors on cells are ineffective; thus the individual
has testes that do not descend and outwardly appears to be female
- Male pseudo-hermaphroditism – an individual appears female until
puberty when anti-Mϋllerian hormone is produced, but the testes
never produce testosterone or DHT

15.4 Pregnancy and birth

• Pregnancy
o The major changes that take place in the mother’s body during pregnancy are due
largely to the effects of the hormones progesterone and oestrogen.
▪ Nausea and vomiting are common symptoms early on (morning sickness).
▪ Some mothers report an overall increase in energy levels and sense of
wellbeing.
▪ Acid reflux and constipation are common problems.
▪ There is an increase in vital capacity.
▪ Edema and varicose veins can result.

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 ▪ Incontinence is not uncommon.
▪ The placenta produces peptide
hormones that make cells resistant to
insulin, so diabetes can result.
▪ Stretch marks are common.
▪ Melanocyte activity increases in some
areas.

• Birth
o The uterus has contractions throughout
pregnancy.
▪ At first these are light, lasting about 20
to 30 seconds and occurring every 15 to
20 minutes.
▪ Near the end of pregnancy, the contractions may become stronger and more
frequent, so that a woman thinks she is in labour.
- “False labour” contractions are called Braxton Hicks contractions.
o Stage 1
▪ During the first stage of labour, the uterine contractions occur in such a way
that the cervical canal slowly disappears as the lower part of the uterus is
pulled upward toward the baby’s head.
- This process is called effacement, or “taking up the cervix”.
o Stage 2
▪ During the second stage of parturition, the uterine contractions occur every
1 to 2 minutes and last about 1 minute each.
- They are accompanied by a desire to push, or bear down.
- As the baby’s head gradually descends into the vagina, the mother’s
desire to push becomes greater.
▪ To enlarge the vaginal orifice, an episiotomy is often performed.
- This incision, which enlarges the opening, is sewn together later.
▪ Once the baby is breathing normally, the umbilical cord is cut and tied,
severing the child from the placenta.
o Stage 3
▪ The placenta, or afterbirth, is delivered during the third stage of parturition.
- About 15 minutes after delivery of the baby, uterine muscular
contractions shrink the uterus and dislodge the placenta.
❖ The placenta then is expelled into the vagina

15.5 Aging
• Aging
o Development does not cease once birth has occurred but continues throughout the
stages of life: infancy, childhood, adolescence, and adulthood.
▪ Infancy, the toddler years, and the preschool years are times of remarkable
growth.
- During the birth to 5-year-old stage, humans acquire gross motor
and fine motor skills.
- Language usage begins during this time and will become increasingly
sophisticated throughout childhood.

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 ▪ The preadolescent years, from 6 to 12 years of age, are a time of continued
rapid growth and learning.
- Preadolescents form identities apart from parents, and peer
approval becomes very important.
- Adolescence begins with the onset of puberty as the young person
achieves sexual maturity.
❖ For girls, puberty begins between 10 and 14 years of age,
whereas for boys it generally occurs between ages 12 and
16.
➢ During this time, the sex-specific hormones cause
the secondary sex characteristics to appear.
➢ Profound social and psychological changes are also
associated with the transition from childhood to
adulthood.
o Aging encompasses the progressive changes from infancy until eventual death.
▪ Gerontology = the study of aging, is of great interest, because there are now
more older individuals in our society than ever before.

• Cellular aging
o Aging is a complex process affected by multiple factors.
▪ Hormonal and genetic influences
▪ Mitochondrial activity
▪ Caloric intake
o Damage accumulation
▪ = Accumulation of cellular damage over time (some avoidable, some
unavoidable).

• Effect of age on body systems

o Skin becomes thinner, less elastic, and dry.
o Less adipose tissue in the skin, so one feels cold more easily.
o Decrease in melanocytes leading to gray hair, while some of the remaining cells are
larger leaving “age spots” (dark spots on the skin).
o Heart shrinks and arteries become more rigid.
o Reaction time slows and senses are muted.
o Lenses in the eyes lose ability to accommodate.
o Blood pressure usually increases.
o Bone density declines.
o Muscle mass decreases.
o Weight gain results from a decrease in metabolism and an increase in inactivity.
o Females undergo menopause and males andropause.

• Conclusion
o We have examined many adverse effects of aging; however, these effects are not
inevitable.
▪ Diet and exercise are factors that are under our personal control.

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16. Patterns of chromosome inheritance
16.1 Chromosomes
• Chromosomes
o The genetic material is arranged into chromosomes.
▪ = Structures that assist in the transmission of genetic information from one
generation to the next.
o The instructions in each chromosome are contained within genes, which in turn are
composed of DNA.
o Chromosomes also contain proteins that assist in the organizational structure of the
chromosome.
▪ Collectively, the DNA and proteins are called chromatin.
o Humans have 46 chromosomes, which occur in 23 pairs.
▪ Twenty-two of these pairs are called autosomes.
- All these chromosomes are found in both males and females.
▪ One pair of chromosomes is called the sex chromosomes, because this pair
contains the genes that control gender.
- Males have the sex chromosomes X and Y.
- Females have two X chromosomes.

• A karyotype
o Any cell in the body except red
blood cells, which lack a nucleus,
can be a source of chromosomes for
examination.
o The display of our chromosomes is a
karyotype (see picture).
▪ It tells us a lot about a body
cell.
- A normal body cell
is diploid (= pair of
chromosome (2n)).
▪ The enlargement of a pair of chromosomes shows that in dividing cells each
chromosome is composed of two identical parts, called sister chromatids.
- They are said to be replicated or duplicated chromosome, because
they contain the same genes.
❖ Genes are the units of heredity that control the cell.
❖ Replication of the chromosomes is possible only because
each chromatid contains a DNA double helix.
▪ The chromatids are held together at a region called the centromere.
- A centromere holds the chromatids together until a certain phase of
mitosis, when the centromere splits.
❖ Once separated, each sister chromatid is a chromosome.

16.2 The cell cycle

• The cell cycle
o Is an orderly process that has two parts: interphase and cell division.
▪ Interphase
- Most of the cell cycle in spent in this part

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 - This is the time when the organelles in the cell carry on their usual
functions.
- As the cell continues through interphase, it gets ready to divide:
❖ The cell grows larger.
❖ The number of organelles doubles.
❖ The amount of chromatin doubles as DNA replication occurs.
- Interphase is divided into three main stages
❖ The G1 stage occurs before DNA synthesis.
➢ The cell returns to normal size and resumes its
function in the body.
➢ A cell doubles its organelles (e.g., mitochondria and
ribosomes), and it accumulates the materials needed
for DNA synthesis.
❖ The S stage includes DNA replication.
➢ A copy is made of all the DNA in the cell.
➢ DNA replication occurs: each chromosome consists
of two identical DNA double-helix molecules.
» These molecules occur in the strands called
sister chromatids.
❖ The G2 stage occurs after DNA replication.
➢ The cell synthesizes the proteins needed for cell
division, such as the protein found in microtubules.
- The amount of time the cell takes for interphase varies widely.
▪ Cell division
- Cell division has two stages: M (for “mitotic”) stage and cytokinesis.
❖ Mitosis is a type of nuclear division.
➢ Mitosis is also referred to as duplication division
» Each new nucleus contains the same number
and type of chromosomes as the former cell.
➢ During mitosis, the sister chromatids of each
chromosome separate, becoming chromosomes
distributed to two daughter nuclei.
➢ Mitosis is balanced by the process of apoptosis, or
programmed cell death.
» Apoptosis occurs when cells are no longer
needed or have become excessively
damaged.
❖ Cytokinesis is division of the cytoplasm.
➢ When cytokinesis is complete, two daughter cells are
now present.
o The cell cycle, including interphase and cell division, occurs continuously in certain
tissues.

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• Cell cycle control
o The cell cycle is controlled by
checkpoints, which can delay
the cell cycle until certain
conditions are met.
▪ Three important
checkpoints: G1, G2
and the mitotic
checkpoint
o In addition, the cell cycle may be controlled by external factors, such as hormones
and growth factors.
▪ Some external signals, such as hormones and
growth factors, can stimulate a cell to go through
the cell cycle.
- Reception: Growth factor activates
receptor
- Signal transduction: Second messenger
cascade
- Gene expression: initiation of gene
transcription + translation
- Response: regulatory proteins
o Failure of the cell cycle control mechanisms may result in
unrestricted cell growth, or cancer.

16.3 Mitosis
• Mitosis
o Mitosis is responsible for new cells in the developing
embryo, foetus, and child.
o It is also responsible for replacement cells in an
adult.
o It is often referred to as duplication division,
because at the conclusion of mitosis the nuclei of the
two new cells have same number and types of
chromosomes as the original cell.
▪ The cell that divides is called the parent cell,
and the new cells are called daughter cells.

• Overview of mitosis (see picture)

o As mitosis begins, the proteins in the chromatin
assist in causing the chromosomes to become highly
condensed.
▪ Once this occurs, the chromosomes become
visible under a light microscope.
o During mitosis, the centromeres divide and the sister
chromatids separate.
▪ Following separation during mitosis, each
chromatid is called a chromosome.

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 ▪ Each daughter cell gets a complete set of chromosomes and is diploid (2n).
- Therefore, each daughter cell receives the same number and types
of chromosomes as the parent cell.
- Each daughter cell is genetically identical to the other and to the
parent cell.

• The mitotic spindle

o Another event of importance during mitosis is the
duplication of the centrosome, the microtubule
organizing centre of the cell.
▪ After centrosomes duplicate, they separate
and form the poles of the mitotic spindle,
where they assemble the microtubules that
make up the spindle fibres.
- The chromosomes are attached to
the spindle fibres at their centromeres.
o An array of microtubules called an aster (because it looks like a star) is also at the
poles.
o Each centrosome contains a pair of centrioles, which consist of short cylinders of
microtubules.
▪ The centrioles lie at right angles to one another.

• Phases of mitosis (for pictures, see book)

o Early prophase
▪ Centrosomes have duplicated.
▪ Chromatin is condensing into chromosomes
▪ Nuclear envelope is fragmenting.
o Prophase
▪ Nucleolus has disappeared
▪ Chromosomes are visible.
▪ Centrosomes begin moving apart
▪ Spindle is in process of forming.
o Prometaphase
▪ Each chromatid is attached to a spindle fiber.
▪ Chromosomes are randomly placed in the nucleus.
o Metaphase
▪ Centromeres of duplicated chromosomes are aligned at the equator (=
centre of fully formed spindle).
▪ Spindle fibres attached to the sister chromatids come from opposite spindle
poles.
o Anaphase
▪ Sister chromatids part and become daughter chromosomes that move
toward the spindle poles.
▪ In this way, each pole receives the same number and kinds of chromosomes
as the parental cell.
o Telophase
▪ Chromosomes arrive at the poles.
▪ Chromosomes become indistinct chromatin again.

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 ▪ Nucleoli reappear.
▪ Spindle disappears.
▪ Nuclear envelope reassembles.

• Cytokinesis
o This is the division of the cytoplasm and organelles.
o In human cells, a slight indentation called a cleavage furrow passes around the
circumference of the cell.
▪ Actin filaments form a contractile ring; as the ring becomes smaller, the
cleavage furrow pinches the cell in half.
▪ As a result, each cell becomes enclosed by its own plasma membrane.

16.4 Meiosis
• Meiosis (= reduction division)
o Reduces the chromosome number in the daughter cells.
▪ To do this, meiosis involves two consecutive cell divisions, without an
intervening interphase.
o The end result is four daughter cells, each of which has one of each type of
chromosome and, therefore, half as many chromosomes as the parent cell.
▪ The parent cell has the diploid (2n) number of chromosomes.
▪ The daughter cells have half this number, called the haploid (n) number of
chromosomes.
o Meiosis introduces genetic variation, which means that each of the resulting
daughter cells is not a genetic replicate of the parent cell.

• Overview of meiosis
o At the start of meiosis, the parent cell is diploid (2n), and the chromosomes occur in
pairs.
▪ The members of a pair are called homologous chromosomes, or
homologues, because they look alike and carry genes for the same traits
(such as type of hair or colour of eyes).
o The two cell divisions of meiosis are called meiosis I and meiosis II.
▪ Prior to meiosis I, DNA replication has occurred and the chromosomes are
duplicated.
▪ During meiosis I, the homologous chromosomes come together and line up
side by side.
- This is called synapsis, and it results in an association of four
chromatids that stay in close proximity during the first two phases of
meiosis I.
▪ Only during meiosis I is it possible to observe paired chromosomes at the
equator.
▪ The time between meiosis I and meiosis II is called interkinesis.

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• The phases of meiosis
o Meiosis I (first picture)
▪ Prophase I
- Homologous chromosomes pair during synapsis.
- An exchange of genetic material may occur between the
non-sister chromatids of the homologous pair.
❖ This exchange is called crossing-over.
▪ Metaphase I
- The homologous pairs align independently at the
equator/metaphase plate.
❖ The maternal or paternal member may be
oriented toward either pole.
▪ Anaphase I
- Homologous chromosomes separate, pulled to opposite
poles by centromeric spindle fibres.
▪ Telophase I
- Daughter cells have one chromosome from each
homologous pair.
▪ Interkinesis
- Chromosomes still consist of two chromatids.
o Meiosis II
▪ Prophase II
- Cells have one chromosome from each homologous pair.
▪ Metaphase II
- Chromosomes align at the
metaphase plate.
▪ Anaphase II
- Sister chromatids separate and move
toward the poles.
▪ Telophase II
- Spindle disappears, nuclei form, and
cytokinesis takes place.
▪ Daughter Cells
- Meiosis results in four haploid
daughter cells.

• Spermatogenesis and oogenesis

o Meiosis is a part of spermatogenesis, the production
of sperm in males, and oogenesis, the production of
eggs in females (together these processes are called
‘gametogenesis’).
▪ Spermatogenesis (power in number)
- Sperm production
- Continual process after puberty.
- ~ 400 million sperm per day.
▪ Oogenesis (size matters)
- Egg production
❖ Meiosis I in embryo (before birth!)

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 ❖ Arrested in Meiosis II, completed after fertilization
- Telophase unequal: 1 egg and 2 (3) polar bodies are formed.
- 1 egg per month (~400 lifetime)

16.5 Comparison of meiosis and mitosis

• Mitosis vs. meiosis
o General comparison
▪ Mitosis
- Growth and repair of cells
- Occurs in body cells
- 1 division
- Results in 2 diploid, genetically identical cells
▪ Meiosis
- Formation of gametes
- Occurs in sex cells
- 2 divisions
- Results in 4 haploid, genetically different cells
o Comparison of the process
▪ Mitosis
- Prophase: no synapsis
- Metaphase: chromosomes align at the metaphase plate
- Anaphase: sister chromatids separate
- Telophase: daughter cells form
- Result: daughter nuclei are genetically identical to parental cell
▪ Meiosis I
- Prophase: synapsis and crossing-over occur
- Metaphase: homologues align independently
- Anaphase: homologues separate
- Telophase: daughter cells form
- After this, meiosis II makes sure that sister chromatids separate
- Result: daughter nuclei are not genetically identical to parental cell

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16.6 Chromosome inheritance
• Changes in chromosome number

o Nondisjunction
▪ Both members of a homologous pair go into the same daughter cell during
meiosis I OR when sister chromatids fail to separate in meiosis II.
o Results of nondisjunction
▪ Monosomy: cell has only 1 copy of a chromosome
- e.g., Turner syndrome (only 1 X chromosome)
▪ Trisomy: cell has 3 copies of a chromosome
- e.g., Down syndrome (3 copies of chromosome 21)
• Genetic inheritance
o Autosomal recessive disorder: cystic fibrosis
▪ Mutation on one of the autosomes
▪ Recessive: healthy gene is dominant -> healthy carrier
▪ 2 mutated alleles to have CF
o Huntington disease
▪ Mutation on one of the autosomes
▪ Dominant: one allele enough to develop syndrome
o Haemophilia
▪ Mutation on X chromosome
▪ Recessive allele only apparent in boys
o Rett syndrome
▪ Located on X chromosome
▪ Affected father: only affected daughters
▪ Affected mother: affected sons and daughters

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17. Cancer
17.1 Overview of cancer
• Cancer
o A disease characterized by uncontrolled cell growth.
▪ Although there are many different types of cancer, and the causes vary
widely, most cancers are a result of a cell accumulating mutations that
ultimately cause a loss of control over the cell cycle.

• Characteristics of cancer cells

o Cancer cells share general traits that distinguish them from normal cells.
▪ Cancer cells lack differentiation
- Differentiation is the process of cellular development by which a cell
acquires a specific structure and function.
- Cancer cells are nonspecialized and do not contribute to the
functioning of a body part.
▪ Cancer cells have abnormal nuclei
- The nuclei of cancer cells are enlarged and may contain an abnormal
number of chromosomes.
- The nuclei of the cervical cancer cells have increased to the point
that they take up most of the cell.
- In addition to nuclear abnormalities, cancer cells often have
chromosomal mutations.
- Ordinarily, cells with damaged DNA undergo apoptosis, or
programmed cell death.
❖ Cancer cells fail to undergo apoptosis, even though they are
abnormal cells.
▪ Cancer cells have unlimited potential to replicate
- Ordinarily cells divide about 60 to 70 times and then just stop
dividing and eventually undergo apoptosis.
- Cancer cells are immortal and keep on dividing for an unlimited
number of times.
▪ Cancer cells form tumours
- Cancer cells have lost all restraint. They pile on top of one another
and grow in multiple layers, forming a tumour.
❖ As cancer develops, the most aggressive cell becomes the
dominant cell of the tumour.
▪ Cancer cells disregard growth factors
- Cancer cells keep on dividing even when stimulatory growth factors
are absent, and they do not respond to inhibitory growth factors.
▪ Cancer cells gradually become abnormal
- Carcinogenesis, the development of cancer, is a multistage process
that can be divided into these three phases:
❖ Initiation: A single cell undergoes a mutation that causes it
to begin to divide repeatedly
❖ Promotion: A tumour develops, and the tumour cells
continue to divide. As they divide, they undergo mutations.

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 ❖ Progression: One cell undergoes a mutation that gives it a
selective advantage over the other cells. This process is
repeated several times; eventually there is a cell that has the
ability to invade surrounding tissues.
▪ Cancer cells undergo angiogenesis and metastasis
- Angiogenesis is the formation of new blood vessels.
❖ The low oxygen content in the middle of a tumour may turn
on genes coding for angiogenic growth factors that diffuse
into the nearby tissues and cause new vessels to form.
- When these cells begin new tumours far from the primary tumour,
metastasis has occurred.
- Malignancy occurs when cancer cells are found in nearby lymph
nodes.

• Cancer results from gene mutation

o Checkpoints in the cell cycle monitor the condition of the cell and regulate the ability
to divide.
▪ Mutations in these checkpoint proteins cause the cell to lose control of the
cell cycle, resulting in cancer.
▪ The two classes of checkpoint proteins are as follows:
- Proto-oncogenes code for proteins that promote the cell cycle and
prevent apoptosis.
❖ They are often likened to the gas pedal of a car, because
they cause acceleration of the cell cycle.
- Tumour suppressor genes code for proteins that inhibit the cell cycle
and promote apoptosis.
❖ They are often likened to the brakes of a car, because they
inhibit acceleration.
o Proto-oncogenes become oncogenes
▪ When proto-oncogenes mutate, they become cancer-causing genes called
oncogenes.
- These mutations can be called “gain-of-function,” or dominant,
mutations, because overexpression is the result.
▪ In general, whatever a proto-oncogene does, an oncogene does it better.
o Tumour suppressor genes become inactive
▪ When tumour suppressor genes mutate, their products no longer inhibit the
cell cycle or promote apoptosis.
- Therefore, these mutations can be called “loss-of-function,” or
recessive, mutations.
▪ Unlike proto-oncogenes, both copies of the tumour suppressor gene in the
cell must be mutated to lose cell cycle control.

• Types of cancer
o The patient’s prognosis (probable outcome) depends on
▪ Whether the tumour has invaded surrounding tissues.
▪ Whether there are metastatic tumours in distant parts of the body.

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 o Tumours are classified according to their place of origin
▪ Carcinomas are cancers of the epithelial tissues, and adenocarcinomas are
cancers of glandular epithelial cells.
- Carcinomas include cancer of the skin, breast, liver, pancreas,
intestines, lung, prostate, and thyroid.
▪ Sarcomas are cancers that arise in muscles and connective tissue, such as
bone and fibrous connective tissue.
▪ Leukaemia’s are cancers of the blood, and lymphomas are cancers of
lymphoid tissue.
▪ A blastoma is a cancer composed of immature cells.
o Common cancers
▪ In the respiratory system, lung cancer is the most common type.
- Overall, this is one of the most common types of cancer, and
smoking is known to increase a person’s risk for this disease.
❖ Smoking also increases the risk for cancer in the oral cavity.
▪ In the digestive system, colorectal (colon/rectum) cancer is another common
form of cancer.
- Other cancers of the digestive system include those of the pancreas,
stomach, oesophagus, and other organs.
▪ In the cardiovascular system, cancers include leukaemia and plasma cell
tumours.
▪ In the lymphatic system, cancers are classified as either Hodgkin or non-
Hodgkin lymphoma.
- Hodgkin lymphomas develop from mutated B cells.
- Non-Hodgkin lymphomas can arise from B cells or T cells.
▪ Thyroid cancer is the most common type of tumour in the endocrine system.
▪ Reproductive system cancers, such as breast cancer in women (although it
occasionally also occurs in men) and prostate cancer in men are some of the
more common forms of cancer.
- Cancers of the cervix, ovaries, and other reproductive structures also
occur in women.
- Other cancers of the male reproductive system include cancer of the
testis and the penis.
▪ Bladder and kidney cancers are associated with the urinary system.
▪ Skin cancers include melanoma and basal and squamous cell carcinomas.

17.2 Causes and prevention of cancer

• Causes of cancer
o Heredity, diet and hormones all have influence on the development of cancer
▪ They are being influenced by
- Some chemicals (tar, asbestos, vinyl chloride, …)
- Some viruses or bacteria (Hepatitis, HIV, HPV, …)
- Radiation (UV light, X-rays, gamma, …)
o Environmental causes of cancer
▪ Mutations induced by radiation
- Purines and pyrimidines absorb ultraviolet light (~260nm) forming
dimers
- Dimers distort the DNA conformation and inhibit replication

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 - X-rays, gamma rays and cosmic rays are high energetic short waves
- Tissue penetration
- Ionization of molecules
❖ Kicking out electrons from atoms
❖ Creating radicals
- Breaking of molecular bonds and structure
▪ Viruses
- Hepatitis B and C viruses can cause liver cancer.
- Human papillomavirus can cause cervical cancer (HPV vaccination)
- HIV and associated herpesvirus (KSHV), can cause Kaposi’s sarcoma
and certain lymphomas.
▪ Nutrition
- Toxins: aflatoxin (mold)
- Acrylamide: at high T° asparagine (aa) reacts with carbohydrates and
forms acrylamide
- Nutrition is emerging as a way to help prevent cancer!

• Prevention of cancer
o Protective behavior
▪ Radiation protection (sunscreen, x-ray)
▪ Avoid carcinogens (smoking, asbestos, toxins, etc.)
o Vaccination (HPV, Hep A + B)

17.3 Diagnosis of cancer

• Diagnosis of cancer
o The earlier a cancer is detected, the more likely it can be effectively treated.
▪ At present, physicians have ways to detect several types of cancer before
they become malignant (= kwaadaardig).
o 7 warning signs
▪ The American Cancer Society publicizes seven warning signals, which spell
out the word CAUTION and of which everyone should be aware:
- C: Change in bowel or bladder habits
- A: A sore that does not heal
- U: Unusual bleeding or discharge
- T: Thickening or lump in breast or elsewhere
- I: Indigestion or difficulty in swallowing
- O: Obvious change in wart or mole
- N: Nagging cough or hoarseness
▪ Keep in mind that these signs do not necessarily mean that you have cancer.
- However, they are an indication that something is wrong and a
medical professional should be consulted.
▪ Unfortunately, some of these symptoms are not obvious until cancer has
progressed to one of its later stages.

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• Routine screening tests
o Early detection increases survival
▪ Cancers develop over years
▪ Screening
- High sensitivity: detection at early stages
- High specificity: false positive/negative
❖ Cervical, colorectal, prostate
▪ Self-examination
- Detecting small changes, increasing awareness
❖ Skin cancer, breast cancer, testicular cancer
▪ High mortality cancers: e.g. pancreas (8% survive first 5y) pose real challenge
o Self-examination, followed by examination by a physician, can help detect the
presence of cancer.
▪ For example, the letters ABCDE can help you examine your skin for
melanoma, the most serious form of skin cancer.
- A = asymmetry
- B = border
- C = colour
- D = diameter (> 6mm)
- E = elevated
o Routine screening tests for cancer
▪ Colonoscopy – every five years starting at age 50
- For gastrointestinal and liver diseases (maag, darm en leverziekten)
▪ Mammogram – yearly after age 50
- For breastcancer
▪ Pap test – should begin three years after vaginal intercourse or no later than
age 21.
o Other ways to detect cancer
▪ Tumor marker tests – blood tests for tumor antigens/antibodies
- CEA (carcinoembryonic antigen) antigen can be detected in someone
with colon cancer
- PSA (prostate-specific antigen) test for prostate cancer
- AFP (alpha-fetoprotein) test for liver tumors
▪ Genetic tests – tests for mutations in proto-oncogenes and tumor suppressor
genes
- RET gene (thyroid cancer)
- P16 gene (associated with melanoma)
- BRCA1/2 (breast cancer)
▪ A diagnosis of cancer can be confirmed by performing a biopsy

17.4 Treatment of cancer

• Standard therapies
o Surgery – removal of small cancers
o Radiation therapy – localized therapy that causes chromosomal breakage and
disrupts the cell cycle
o Chemotherapy – drugs that treat the whole body and kill cancer cells by damaging
their DNA or interfering with DNA synthesis
o Bone marrow transplants – transplant bone marrow from one individual to another

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18. DNA biology and technology
18.1 DNA and RNA structure and function
• What does DNA do?
o Function
▪ DNA stores information.
▪ It replicates to be passed on to the next generation (cell division).
▪ It undergoes mutations to provide genetic diversity.
o 3 billion base pairs
▪ 50-300 Mio base pairs /chromosome
▪ 30 000 genes → proteins
o Structure
▪ It is a double-stranded helix.
▪ DNA is composed of repeating nucleotides (made of a pentose sugar,
phosphate, and a nitrogenous base).
- Sugar and phosphate make up the backbone, while the bases make
up the “rungs” of the ladder.
▪ Bases have complementary pairing:
- Cytosine (C) with guanine (G),
- Adenine (A) with thymine (T).
▪ DNA in anti-parallel configuration
▪ 3’ and 5’ refers to the carbon molecule on the deoxyribose
- This is important for the direction of
❖ Replication
❖ Transcription

• Replication of DNA
o When cells divide, each new cell gets an exact copy of DNA.
▪ The process of copying a DNA helix is called DNA replication.
o DNA replication is termed semiconservative, because each new double helix has one
original strand and one new strand.
▪ In other words, one of the original strands is conserved, or present, in each
new double helix.
o Each original strand has produced a new strand through complementary base
pairing, so there are now two DNA helices identical to each other and to the original
molecule.
o The major events in DNA replication include:
▪ The enzyme DNA helicase unwinds and “unzips” double-stranded DNA by
breaking the weak hydrogen bonds between the paired bases.
▪ New complementary DNA nucleotides (composed of a sugar, phosphate, and
one nitrogen-containing base), always present in the nucleus, are fit into
place by the process of complementary base pairing.
- These are positioned and joined by the enzyme DNA polymerase.
▪ Because the strands of DNA are oriented in an antiparallel configuration, and
the DNA polymerase may add new nucleotides onto one end of the chain,
DNA synthesis occurs in opposite directions.

136
 - The leading strand follows the helicase enzyme, while synthesis on
the lagging strand results in the formation of short segments of DNA,
called Okazaki fragments.
▪ To complete replication, the enzyme DNA ligase seals any breaks in the
sugar-phosphate backbone.
- The DNA returns to its coiled structure.
▪ The two double-helix molecules are identical to each other and to the
original DNA molecule.

• The structure and function of RNA

o Ribonucleic acid
o Single-stranded.
o Composed of repeating nucleotides.
o Sugar-phosphate is the backbone.
o Bases are Adenine, Cytosine, Guanine, and uracil (U).
o There are three major types of RNA
▪ Messenger RNA (mRNA) carries genetic information from DNA to the
ribosomes.
▪ Ribosomal RNA (rRNA) joins with proteins to form ribosomes.
▪ Transfer RNA (tRNA) transfers amino acids to a ribosome to make
polypeptide chain.
o Another type of RNA: Small RNA
▪ They are divided into several classes.
▪ Small nuclear RNAs (snRNAs) are involved in splicing the mRNA before it is
exported from the nucleus to the cytoplasm for translation.
▪ Small interfering RNAs (siRNAs) also bind to mRNAs.
- Attachment of an siRNA prepares the mRNA for degradation.
• Comparison of DNA and RNA
o Similarities
▪ Nucleic acids
▪ Composed of nucleotides
▪ Sugar-phosphate backbone
▪ Four different types of bases
o Differences

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18.2 Gene expression
• Gene expression
o As we will see, DNA provides the cell with a blueprint for synthesizing proteins.
▪ In simplest terms, DNA acts as a template for making RNA, which in turn acts
as a template for the manufacture of proteins.
o In gene expression, also known as protein synthesis, the process of transcription
makes an RNA copy of DNA, and the process of translation makes protein from the
RNA.
o Two steps of gene expression
▪ Transcription (= to make a faithful copy)
- DNA is copied into mRNA
❖ mRNA is made from a specific DNA template.
➢ Only the gene of interest is transcribed from
template strand
➢ Transcription starts at specific point: transcription
initiation site
➢ Transcription stops at specific termination point
➢ mRNA is processed and leaves nucleus
- Processing of mRNA after transcription
❖ DNA contains regions that
➢ Encode a protein (Exon)
➢ Do not encode (Intron)
❖ Both exons and introns are transcribed to mRNA.
❖ During maturation, introns are removed
▪ Translation
- At ribosomes, mRNA is translated into a protein (cytoplasm)
❖ Matured mRNA trans-locates to ribosomes (leaves nucleus)
❖ Codon: genetic code corresponds to a three base (letter)
sequence in mRNA (=codon)
➢ How genetic encoded information is translated into
proteins
» The four bases (A/U,G/C) can form a unique
triplet code (codon)
» Bases act as a code for 20 different amino
acids used in translation.
» Reading frame: Where to start? => start
codon (AUG)
» Reading frame: where to stop? → stop
codon
❖ Each codon represents/encodes one amino acid (aa)
- 3 steps in translation
❖ Initiation: assembly of ribosomes
➢ mRNA binds to the small ribosomal subunit and
causes the two ribosomal units to associate
❖ Elongation: assembly of polypeptide chain
➢ tRNA picks up an amino acid.
➢ tRNA has an anticodon that is complementary to the
codon on the mRNA.

138
 ➢ tRNA anticodon binds to the codon and drops off an
amino acid to the growing polypeptide.
❖ Termination: release of polypeptide chain
➢ A stop codon on the mRNA causes the ribosome to
fall off the mRNA

139
 19. Clinical topic 1: Covid 19 due to SARS-Cov-2
50% van het examen staat op de klinische topics

• Clinical case
o 52 year old man, BMI 34, takes drugs for hypertension (hoge bloeddruk)
o For 7 days already : fever 38,6, very tired, anorexia
o 3 days ago shortness of breath, could not talk very well, admission in the hospital.
▪ PCR Diagnosis of Covid-19.
▪ R/oxygen therapy
o Evening of the day of admission (-3 days):
▪ Worsening (Oxygen saturation < 70%)
▪ Admission on intensive care
▪ R/ artificial ventilation, steroid therapy
▪ Krijgt ook medicatie tegen inflammatie (ontsteking), dus cortisone en
steroïde
o Today: multi-organ failure and myocardial infarctions, collaps/shock
o “Died at 19.53”

• Covid-19
o Is een luchtweginfectie waarvan het beloop mild kan zijn, maar ook zeer ernstig met
ziekenhuisopname en sterfte tot gevolg;
o Wordt veroorzaakt door een infectie
met een nieuw coronavirus, het SARS-
CoV-2 virus, dat eind 2019 voor het
eerst bij mensen werd gedetecteerd.
o Coronavirussen
▪ Veel verschillende types
- 7 gekend bij de
mensen:
❖ 4 zijn
endemisch
globaal en zijn verantwoordelijk voor
10-30% van de besmettingen
➢ Milde symptomen:
veelvoorkomende verkoudheid
❖ 3 zijn heel besmettelijk/ziekmakend
(geweest):
➢ SARS – 2002 – SARS-CoV
➢ MERS – 2012 – MERS-CoV
➢ SARS-CoV2 – 2019
❖ Dat wil dus zeggen dat veel van ons
waarschijnlijk vroeger al besmet zijn
geweest met een coronavirus, maar die
waren niet zo ziekmakend als deze.

140
• Besmettingen
o Het coronavirus (SARS-CoV-2) is een besmettelijk virus. Je kan het makkelijk van
andere mensen krijgen of doorgeven.
o Overdracht van SARS-CoV-2 van persoon tot persoon:
▪ Door direct contact met druppeltjes van een geïnfecteerde persoon die
hoest, niest of spreekt (80% van de besmettingen)
▪ Door indirect contact als druppeltjes of secreties op handen of oppervlakken
komen (deurklinken, kranen…). Zo kan het virus andere mensen bereiken als
die met besmette handen hun gezicht aanraken.
o Risico op besmetting is het grootst bij langdurig nauw contact: meer dan 15 minuten
op minder dan 1,5m
o Incubatieperiode: 2-14 dagen (gemiddeld 5-6 dagen)
o Besmettelijke periode: begint 48u voor eerste symptomen tot 7 dagen na de start
van symptomen (uitzonderingen zijn kwetsbare mensen)

▪ Het RNA van het virus kan op zichzelf

niets doen.
- Heeft lysosomen, mRNA, etc.
nodig om zich te verspreiden.
o Komt binnen via nasale/ademhalingsmucosa
o Meest voorkomende doodsoorzaak en
morbiditeit is ademhalingsproblemen
▪ Dat leidt verder tot multiorgaan falen:
- Longen
- Hersenen
- Hart
- Lever
- Nieren

• Hoe COVID-19 herkennen?

o Begin: meestal plotse hoge koorts (>38,5°C) en hoest.
o Eerste symptomen treden gewoonlijk 4 tot 5 dagen na de besmetting op, soms
vroeger (minstens na 2 dagen) of later (tot max. 14 dagen).

• Symptomen
o De belangrijkste symptomen zijn:
▪ Hoest
▪ Kortademigheid
▪ Pijn of drukkend gevoel op de borst
▪ Koorts (of verhoging)

141
 - Bacteriën en virussen kunnen niet tegen
hoge temperaturen, vandaar dat ons
lichaam koorts aanmaakt, zodat we die
virussen/bacteriën doden
▪ Spierpijn
▪ Vermoeidheid
▪ Verlies van geur- en smaakzin
▪ Verstopte neus
▪ Keelpijn
▪ Diarree
o De besmetting kan ook asymptomatisch verlopen

• Afbeelding van longen

o Pneumonie (klein cirkeltje links) = longontsteking
o Astma = de luchtwegen naar de longblaasjes vallen veel te
snel dicht (klein cirkeltje rechtsonder)

• Wat is ARDS
o Acute respiratory distress syndrome
o Serieuze longinfectie dat laag zuurstofniveau
veroorzaakt
▪ Vloeistof bouwt zich op in de
luchtzakjes in uw longen, wat leidt
tot verlies van surfactant (helpt de
luchtzakjes openhouden bij het
inademen), dat leidt op zijn beurt tot
lage zuurstofgehaltes en dat kan
uiteindelijke eindigen in
littekenweefsel.
o Er bestaat een hart-longmachine dat de longen overneemt, wat hier als behandeling
kan gebruikt worden.
▪ Je kan ook perfect leven met één long, maar dan moet je al serieus indijken
in longcapaciteit en dat brengt ook gevolgen met zich mee.

Kinderen kunnen ook ziek worden van het virus, dat komt omdat hun ACE2 receptoren nog heel fel
aan het ontwikkelen zijn.

142
• Diagnose
o Zonder test geen onderscheid tussen andere luchtweginfecties en COVID-19
o Op basis van een PCR-test wordt bepaald of een persoon COVID-positief is
▪ Testing ten gevolge van hoog risico contact of symptomen
o Strategieën
▪ Detection of the virus RNA genetic material (Nucleic acid test)
- Strategy based on Polymerase Chain Reaction technique (PCR)
- From a few DNA copies and thanks to iterative cycles of, high yield of
genetic material can be obtained, detected using fluorescent labels
- Voordelen:
❖ Gevoeligheid, sensitiviteit ligt zeer hoog: betrouwbaarheid!
- Nadelen:
❖ Zeer arbeidsintensief, zeer kostelijk
▪ Detection of the intact virus (antigen detection test)
- Detection of the intact virus through the outer virus proteins (viral
antigens) by using specific antibodies
- Voordelen:
❖ Sneller resultaat, lage kosten, hoge productie, …
▪ Detection of antibodies (serological test)
- Detection of antibodies produced by the infected person during he
disease (detection of antibodies present in blood/Serum samples)
• Gevolgen van Covid-19
o Meeste mensen (+-80%) maken COVID-19 asymptomatisch door of vertonen milde
symptomen, zonder noodzaak tot hospitalisatie
o Zonder bijkomende complicaties is de zieke na ongeveer 1 week genezen
o Bij ongeveer 20% zijn er complicaties:
▪ Tekort aan zuurstof
▪ Bloedvergiftiging met of zonder shock
▪ Ontstaan van bloedklonters
▪ Uitval van meerdere organen
▪ Overlijden
o Complicaties kunnen bij iedereen voorkomen maar zijn frequenter bij:
▪ 65-plussers
▪ Mensen met onderliggende aandoeningen, bv. te hoge bloeddruk, hartlijden,
longlijden, suikerziekte, ernstig overgewicht, kanker, nier- en leverziekten
o Lange-termijn gevolgen (denk aan Long-Covid):
▪ Aanhoudende moeheid
▪ Ademhalingsproblemen
▪ Verlies van reuk en smaak
▪ Hoesten
- Opgelet: dit wil niet per se zeggen dat longen niet slecht werken,
maar de patiënten blijven wel negatieve gevolgen ervaren (zonder
dat het af te leiden is uit medische onderzoeken)

• Pandemie
o Wereldwijd: (week 10, 2021)
▪ 120 268 427 mensen met een bewezen infectie door COVID-19
▪ 2 659 802 overleden

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 o In België: (22 maart 2021)
▪ 837 006 mensen met een bewezen infectie door COVID-19
▪ >22.000 overleden
- Totaal overlijdens als gevolg van Covid-19: 22 707

• Herbesmetting
o Na genezing van COVID-19 kunnen er antilichamen in je lichaam aanwezig zijn.
o Deze antilichamen bieden kortstondig (2 maanden) en onvolledig bescherming.
o Herbesmetting is mogelijk!

• Hoe voorkomen?
o 7 gouden regels
▪ 1. Respecteer de hygiënemaatregelen
- Regelmatig handen wassen met water en zeep of alcoholische
handgel gebruiken
- Nies- en hoesthygiëne:
❖ Gebruik papieren zakdoekjes
❖ Gooi de zakdoekjes in de vuilbak na eenmalig gebruik
❖ Bedek bij niezen of hoesten de neus/mond met een
zakdoekje, de voorarm of elleboog
- Raak zo min mogelijk je mond, neus of ogen aan.
- Als je ziek bent, blijf dan thuis en contacteer je huisarts.
▪ 2. Organiseer je activiteiten buiten
▪ 3. Denk aan kwetsbare mensen
▪ 4. Hou afstand (1,5m)
▪ 5. Beperk je nauwe contacten
▪ 6. Draag je mondmasker
▪ 7. Beperk bijeenkomsten
o Vaccinatie
▪ Hoe werkt het?
- Na het inspuiten van een vaccin maakt je afweersysteem antistoffen
en specifieke afweercellen aan om de virusdeeltjes te bestrijden. Dit
kost tijd.
- Bij blootstelling nadien aan
echt virus: je afweersysteem
herkent het virus, en kan
sneller in actie komen.
- Hierdoor worden mensen niet
ziek of zijn de klachten
minder ernstig.
▪ Verschillende merken
- Beschikbaar
❖ Pfizer-BioNTech:
Comirnaty®
❖ Moderna
❖ AstraZeneca
❖ Johnson & Johnson

144
 - In ontwikkeling/goedkeuring
❖ Curevac
❖ Sanofi-GSK
▪ mRNA-vaccins, hoe werken ze?
- Het Pfizer en Moderna vaccin
zijn mRNA-vaccins.
- mRNA stimuleren het lichaam
om het stekeleiwit van het virus
zelf aan te maken.
- Dit eiwit circuleert maar kort in
je lichaam, ook het mRNA
verdwijnt snel.
- Voorts verloopt het proces als
bij een klassiek vaccin
▪ Werkzaamheid Pfizer en Moderna
vaccin
- Effectiviteit: 100% bescherming
tegen ernstige ziekten
- Duur werking: studies tonen
minstens 2 maanden aan, maar
er wordt voorzichtig geschat op
1 jaar.
▪ Vector vaccins, hoe werken ze?
- Het AstraZeneca en Johnson & Johnson vaccin zijn vector vaccins.
❖ AstraZeneca-vaccin
➢ Doelgroep: 18+
➢ Effectiviteit is zeer goed
» Tegen ernstige infecties + hospitalisatie
 94% 28-34 dagen na dosis 1
 100% 14 dagen na dosis 2
» Tegen milde infecties
 80% 14 dagen na dosis 2
➢ Duur werking: studies tonen minstens 2 maanden
aan, maar er wordt voorzichtig geschat op 1 jaar.
❖ Johnson & Johnson vaccin
➢ Doelgroep: 18+
➢ 1 dosis
➢ Effectiviteit
» Tegen ernstige infecties + hospitalisatie
 76,7% 14 dagen na vaccinatie
» Tegen milde infecties
 66,9% 14 dagen na vaccinatie
➢ Duur werking: studies tonen minstens 2 maanden
aan, maar er wordt voorzichtig geschat op 1 jaar.

145
 - Onderzoekers passen bestaande virussen aan zodat het geen
levende virussen meer
zijn, maar vectoren die het
spike-eiwit tot expressie
brengen. De virussen zijn
niet langer ziekmakend en
kunnen zich niet meer
vermenigvuldigen. Ze
stimuleren wel je
afweersysteem om
antilichamen te maken
tegen de spike-eiwitten,
en je T-cel immuniteit te
activeren.

• AstraZeneca-vaccin en bloedklonters
o ‘Trombose’: verzamelnaam van een reeks ziekteverschijnselen, waaronder een
aantal zeer zeldzame ziektebeelden, zoals de combinatie van tromboses en
trombocytopenie.
o Hoeveel? 25 voorgevallen op 20 miljoen gevaccineerden
o Er is wetenschappelijk gezien geen verband tussen vaccinatie en een hoger risico op
tromboses.
o Voordelen van het vaccin bij de bestrijding van COVID-19 wegen op tegen het risico
op bijwerkingen.
o Symptomen 4-14 dagen na vaccinatie: contacteer arts
▪ Kortademigheid
▪ Pijn op de borst en in de maag
▪ Zwelling en kou in een lidmaat
▪ Ongewone, zeer hevig hoofdpijn, vooral als deze verergert en/of niet
reageert op een pijnstillende behandeling
▪ Troebel/wazig zicht
▪ Aanhoudende bloedingen met of zonder significante trombocytopenie
▪ Verscheidene kneuzingen, roodachtige/paarse petechiën, hemorragische
blaasjes.

• Waartegen beschermt het COVID-vaccin

o Het vaccin beschermt tegen het ziek worden door een COVID-19 besmetting.
o Het vaccin vermindert de klachten bij matige tot ernstige ziekte bij het doormaken
van COVID-19.
o Het vaccin beschermt tegen ernstig verloop van COVID19 (bv. hospitalisatie)
o Verwacht: het vaccin verhindert de verspreiding bij een hoge vaccinatiegraad.
o Hoe lang het beschermt weten we nog niet.

• Veiligheid COVID vaccin?

o Grondig, diepgravend en voortgezet wetenschappelijk onderzoek naar de veiligheid
en werkzaamheid van het vaccin werd en wordt blijvend uitgevoerd.
o Geneesmiddelenveiligheidsbewaking is een uiterst betrouwbaar
controlemechanisme en heeft zijn nut al bewezen.

146
 o Ook onder de huidige hoogdringende context zijn er geen toegevingen gedaan aan
de hoge standaard van deze kwaliteitscontrole.
o De vaccinontwikkelaars willen tonen wat ze kunnen. Iedereen heeft op zijn terrein
gedaan wat mogelijk was om zo weinig mogelijk tijd te verliezen.

• Kan het vaccin zelf COVID-19 veroorzaken?

o Het vaccin bevat geen levend virus en kan dus geen COVID-19 veroorzaken.
o Kort na de vaccinatie toch ziek?
▪ Kort voor of na de inenting besmet: het duurt 10 à 14 dagen na de eerste
vaccinatie vooraleer je lichaam antistoffen ontwikkelt die goed beschermen
=> blijf de maatregelen goed volgen!
▪ De eerste dagen na vaccinatie kan je bijwerkingen vertonen
▪ Grieperig ziektebeeld door een ander virus

• Wat als je je niet laat vaccineren?

o Je hebt zelf geen bescherming, en je kan nog een besmettingsbron worden voor
anderen. Zelfs als je al eens besmet werd in het verleden.
o Je draagt niet bij aan de groepsimmuniteit.
o Verplicht in de zorg?
▪ Neen, alleen sterk aanbevolen.

• Wat met de maatregelen?

o We streven naar minstens 70% vaccinatie van de bevolking om groepsimmuniteit te
bereiken.
o Afhankelijk van de vaccinatiegraad en druk op het gezondheidszorgsysteem zullen
wijzigingen in de veiligheidsmaatregelen al dan niet mogelijk worden.
o Momenteel: na het ontvangen van een vaccinatie wijzigen de coronamaatregelen
niet.

147
20. Clinical topic 2: acute myocardial infarction (= acuut hartinfarct)
• Clinical case
o Woman of 61 , diabetes, BMI 29, secretary, sedentary life style
o Last 2 years: several episodes of chest pain for 1-5 minutes
o During cycling: acute pain thorax and left arm, persistent, shortness of breath, fall
and not reacting well
o Ambulance: oxygen, painkiller (morphine)
o Emergency department: ECG (electro cardiogram): ST elevation
o Diagnosis: Acute myocardial infarction
o R/ acute thrombolysis during catheterisation
o Outcome OK, treatment started with statins and aspirin for secondary prevention

• Hoe onstaat een hartinfarct?

o Ieder bloedvat heeft een kringvormige spier
▪ Het is tamelijk complex, ook al lijkt het niet zo
o De bloedvaten waar het hier over gaat zijn de bloedvaten die zorgen voor de
zuurstofbedeling van de hartspier zelf (= de coronaire bloedvaten)
▪ 3-tal grote coronaire bloedvaten, met veel vertakkingen
o Bij een hartinfarct: een van de bloedvaten is niet meer doorgankelijk voor bloed
(=atherosclerose).
▪ Een bepaalde zone krijgt geen bloed en dus zuurstof meer, en dat deel van
het hart sterft af.
o Waar kunnen er vooral problemen optreden met atherosclerose?
▪ Vooral in coronaire materies, dus rond het hart.
▪ Maar ook veel cerebrovasculair, dus in de hersenen.
o Het is een ziekte die langzaam ontwikkelt en verloopt en uiteindelijk zich op een
ernstige manier zal uiten en kan leiden tot de dood.

• Atherosclerose / atheromatose
o 2 manieren waarop het kan ontstaan
▪ Ofwel groeit de verkalking geleidelijk aan
totdat het bloedvat volledig dichtzit
▪ Ofwel ontstaat er een scheur in het bloedvat,
waardoor ons lichaam dit wil dichtdoen door
te stollen (dit komt het meeste voor bij
mensen met een acuut hartinfarct).
- Hierdoor ontstaat er een trombose of
een bloedklodder op de
atherosclerose.
- Medicatie die hierbij kan helpen
❖ Statine: zorgt ervoor dat die
atheromatose of
atherosclerose plak zo klein mogelijk blijft.
❖ Aspirine: zorgt ervoor dat er geen bloedklonter gaat
ontstaan op die atherosclerose plak.
o Kan ook ter hoogte van de nieren, de hersenen, maar vooral ter hoogte van het hart.
▪ Als het ter hoogte van de hersenen plaatsvindt: ontstaan van een beroerte.

148
 o Atheromatose plak
▪ Is een traag en progressief opbouwende plakkerige, vettige substantie
bestaande uit cholesterol, cellulair afval, producten, calcium, …
o Risicofactoren
▪ Grote risicofactoren (waar je niets aan kan veranderen)
- Toenemende leeftijd
- Mannelijk geslacht
- Familiegeschiedenis
- Genetische afwijkingen
▪ Kleinere risicofactoren, zijn minder aanwezig (staat wetenschappelijk nog
niet vast)
- Obesitas
- Fysieke beweging
- Postmenopauzale oestrogeen tekort
- Hoge inname van koolhydraten, te veel suiker
- Lipoproteïnes
- Inname van onverzadigde vetten
- Chlamydia infectie (chronische infectie)
▪ Risicofactoren die te vermijden zijn
- Hyperlipidemie (een te hoog cholesterolgehalte)
❖ Te hoog vetgehalte, te hoog cholesterolgehalte
❖ LDL (vetpartikel in je bloed, slechte cholesterol)
➢ Brengt vet naar je bloedvaten
❖ HDL (high density lipoprotein)
➢ Brengt vet naar je lever om daar verder verwerkt te
worden
- Hoge bloeddruk
❖ Moet regelmatig gecontroleerd worden
❖ Moet normaal 80 over 120 zijn.
➢ Vanaf hoger dan 80 en 120, stijgt uw risico op een
hartinfarct.
❖ Dit is een stille doder (vaak weet je het niet dat je het hebt,
totdat het zich volledig manifesteert).
- Roken
❖ Als je een pakje sigaretten per dag rookt, stijgt het risico op
overlijden met 200%
- Diabetes, hangt samen met obesitas
- C-reactief proteïne

• Factoren die uw cholesterolgehalte (LDL en HDL)mee bepalen

o Er is een genetische factor, maar we kunnen veel aanpassen met een dieet
▪ Goede vetten kiezen (visvetten), zorgt voor een lage LDL en een hoge HDL
- Vlees vetten zijn slecht
o Oefeningen, sport, maar ook 2 glazen alcohol per week zijn goed om onze HDL
omhoog te krijgen
▪ Obesitas en roken zorgen er dan weer voor dat deze HDL omlaag gehaald
wordt

149
 o Medicatie
▪ Statines dagelijks innemen zorgt voor een verlaging van de LDL
- Werkt op een metabole manier, dus uw cholesterol wordt niet meer
aangemaakt. Dit zijn zeer sterke medicaties om uw cholesterol laag
te houden.
• Hartinfarct
o Door te kijken welke plaats in je hart afgestorven is, kunnen ze kijken waar het
hartinfarct is ontstaan.
▪ Soms kan het herstellen, soms is dit wat moeilijker (en dan is het niet meer
acuut).
o Veel voorkomende symptomen
▪ Pijn in de borstkas (meest voorkomende)
- Straalt vaak uit naar de linkerarm of de kaak
▪ Licht in het hoofd, misselijk, braken
▪ Pijn in de nek, kaak, rug
▪ Kortademigheid (dyspnea)
▪ Soms ook pijn in de arm en schouder
▪ Hartkloppingen
▪ Verlies van bewustzijn
▪ Plotse dood, enkel wanneer het heel ernstig is.
o Acuut hartinfarct
▪ Het zuurstoftekort heeft te lang geduurd, waardoor een deel van je hart
kapot is en dus niet meer kan herstellen.

• Termen
o Patiënten met IHD (ishemic heart disease), dus zij die
niet genoeg zuurstoftoevoer krijgen naar het hart,
kunnen we opdelen in 2 grote groepen
▪ Patiënten met CAD (coronary arteries disease)
- Zij zitten in het beginstadium en
hebben nog een stabiele angina (pijn
aan de borstkas)
▪ Patiënten met acute coronary syndrome
- Onstabiele angina, is veel langduriger
en ernstiger
- Hebben een acute myocardial infarction
❖ STEMI (ST-Elevation)
o Stabiele vs. onstabiele angina

▪ Je kan overgaan van stabiele naar onstabiele angina.

▪ Als je patiënten goed behandeld, kunnen sommige patiënten lang leven met
een stabiele angina.

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• Levensstijl
o Letten op je voeding, minder vetten en suikers, enkel nog goede vetten!
o Maar er zijn natuurlijk ook oorzaken en factoren waar we niets aan kunnen doen, en
dat is zeer vervelend voor geneeskundigen.

• Behandeling
o Men probeert de bloedvaten weer open te krijgen, waardoor het bloed weer kan
verder stromen
▪ Het hart kunnen ze vaak niet meer herstellen, maar ze kunnen wel proberen
te vermijden dat er weer een verkalking in de bloedvaten ontstaat.
o Hiervoor gaan ze een stof inspuiten, waardoor de trombose gaat oplossen en het
bloed weer verder kan stromen (= trombolyse)
o Een andere optie is een stent plaatsen, waardoor het bloedvat open blijft.
o Bypass operatie: gezonde bloedvaten opzoeken en zo nieuwe wegen creëren om uw
hart te voorzien van genoeg bloed en dus zuurstof.

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21. Clinical topic 3: borstkanker
• Clinical case
o 42 year woman
o During sport activity: extreme pain in the back (lumbar region)
o Diagnosis: muscle pain due to exercise R/ painkillers and rest
o Two weeks later: feels ‘lump’ in the left breast
o Diagnosis with mammography: breast cancer (with bone metastasis)
o Biopsy and staging: stage IV
o R/ lumpectomy, chemotherapy, local spine radiation therapy
o Now 2 years in follow up (breast reconstruction planned)
o Genetics: BRCA2 positive: implications for her 2 daughters, 15 and 19 year old

• Hoe ontstaat kanker?

o Gebeurt in stappen
▪ Invasie
- Kankercellen groeien in de omliggende weefsels en bloedvaten
▪ Metastase
- Kankercellen worden getransporteerd door de bloedsomloop naar
de nabije sites
- Kankercellen groeien op hun nieuwe locatie
o Proces

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 • Oorzaken
o De hoeveelheid rood vlees dat u eet per dag
▪ Vooral bij longkanker
o Roken
▪ Aantal sigaretten per dag, vanaf 15 sigaretten per dag is het risico op
longkanker 15x hoger.
o Zonlicht of X-rays
▪ Door bestraling
o Infecties (virussen, bacteriën)
o Genetica: bij borstkanker speelt dit een zeer grote rol.

Zeer positief: de laatste jaren zien we dat mensen minder roken en minder rood vlees eten!

• Borstkanker
o De normale borst: opdeling

o Het lymfatisch systeem

▪ Bestaat uit vaten en organen en speelt 2 vitale rollen in ons leven
- De bloedvaten behouden onze vloeistoflevels
- De organen zorgen voor onze lichaamsverdediging tegen infecties
o Twee soorten
▪ Benning tumoren (goedaardige gezwellen)
- Geen kanker!
▪ Kwaadaardige tumoren, kunnen we opdelen in
- Invasief
❖ Bevatten kanker
❖ Zijn kwaadaardig
❖ Gaat zich verspreiden naar andere organen (metastase)
- Niet-invasief
❖ Pre-kanker
❖ Nog in zijn originele positie
❖ Zal uiteindelijk ontwikkelen tot een invasieve borstkanker

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o Twee grote structuren waar de kankers kunnen voorkomen
▪ Afvoerkanalen van de melk
- 80% van de kankers vindt hier plaats
▪ Lobules waar melk geproduceerd wordt
o Soorten borstkanker
▪ Ductal carcinoma
- Niet invasief
- Waar de melkkanalen gelegen zijn
- Kan invasief worden
- 80% begint hier (en breidt uiteindelijk uit naar andere organen)
▪ Inflammatory breast cancer
▪ Lobular carcinoma
- Veel minder frequent (10%)
- Ontstaat in de lobules, op dat moment nog perfect behandelbaar
- Groeit door de wand van die lobules
- Maar kan door metastase uitbreiden en naar de lymfen uitbreiden.
o Risicofactoren
▪ 1/11 vrouwen zal borstkanker meemaken in haar leven, dus zeer frequente
aandoening
▪ Kanker
- Geslacht (mannen kunnen ook borstkanker ontwikkelen, maar dit is
veel minder frequent)
- Leeftijd: hoe ouder, hoe meer kans
❖ 80% ontstaat boven de leeftijd van 50j.
- Genetische risicofactoren
❖ Geboren worden met een mutatie en een variant
➢ BRCA1 en BRCA2 zijn niet alleen risicofactoren voor
borstkanker, maar voor verschillende soorten
kanker.
- Familiegeschiedenis
- Persoonlijke geschiedenis
▪ Borstkanker
- Ras, etnische achtergrond
- Dicht borstweefsel
- Problemen met hormonale huishouden
- Bestraling van de longen in het verleden
▪ Andere factoren die hiertoe bijdragen
- Het niet hebben van kinderen of pas op latere leeftijd
- Verschillende anticonceptiemiddelen
- Hormoontherapie na menopauze
- Geen borstvoeding geven
- Alcohol
- Overgewicht of obesitas
- Tabak
- Nacht werk
o Signalen en symptomen
▪ Een bolletje, een gezwel in de borst
▪ Pijn in de oksels dat niet te verwijten is aan de menstruatie

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 ▪ Roodheid van de huid of de borst, of putjes in de huid (appelsienenhuid)
▪ Uitslag op of rond de tepels
▪ Een gezwel in de oksels
▪ Een verdikt weefsel in de borst
o Diagnose methoden
▪ Borstonderzoek
- Vanaf de leeftijd van 20j en 30j zouden vrouwen elke 3 jaar een
borstonderzoek moeten doen
- Na de leeftijd van 40j zou dit elk jaar moeten gebeuren
▪ Mammogram
▪ Ultrasound
▪ MRI scan
▪ Biopsie
o Fases van borstkanker
▪ TNM fase systeem
- Tumor grootte en uitspreiding (T)
- Of de kanker zich verspreid heeft naar lymfen (N)
- Of de kanker zich verspreid heeft naar de nabije organen voor
metastase (M)
▪ De verschillende fasen
- Fase 0: niet-invasief, nog niet verspreid
- Fase 1: gezwel is < 2cm, maar is nog niet verspreid
- Fase 2
❖ A: < 2 cm en verspreid naar de lymfen OF 2-5 cm en niet
verspreid
❖ B: 2-5 cm en verspreid naar lymfen OF > cm en niet verspreid
- Fase 3
❖ A: < 5 cm en verspreid om klonters te ontwikkelen OF >5 cm
en verspreid, maar geen klonters ontwikkelen
❖ B: eender welke grootte en verspreid naar de huid en de
borstwand
❖ C: eender welke grootte en verspreid naar de lymfen, huid
en de borstwand
- Fase 4: metastase.
o Behandeling
▪ Hangt af van
- Het type borstkanker
- De fase waarin de kanker zich bevindt
- Of het gevoelig is voor hormonen
- De algemene gezondheid van de patiënt
- De leeftijd van de patiënt
- De eigen voorkeuren van de patiënt
▪ Kan bevatten
- Operatie
- Radiatie therapie
- Biologische therapie
- Hormoontherapie: voor borstkankers die gevoelig zijn aan hormonen
- Chemotherapie

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22. Clinical topic 4: inflammatory bowel disease (IBD)
• Clinical case
o 31 year old male
o Start problems: age 27, no significant medical history
o For 3 weeks , decreased appetite, diarrhoea (sometimes bloody) and painful
abdominal cramps
o Weight loss -2kg/week
o Painful aphtous ulcers on the lips
o Family doctor: ‘ gastro-enteritis’, stool culture negative
o No improvement: coloscopy: diagnosis of ‘Colitis Ulcerosa’
o Acute treatment: 5-ASA and prednisone
o Chronic treatment: 5-ASA
o Last years: several episodes of rectal blood loss and diarrhoea, low fever

• What is inflammatory bowel diseases?

o Ziektes van maagdarm-systeem (buis met uitstulping, namelijk de maag)
o IBD is characterized by
▪ Chronic, immune-mediated inflammation in the gastrointestinal (GI) tract
- Chronisch, dus kan levenslang duren.
- Inflammatie = reactie van ons lichaam op een ontsteking
▪ Often has a progressive, destructive course
o The two major forms of IBD are Chron’s diseases (CD) and ulcerative colitis (UC)
▪ CD is iets erger dan de tweede vorm.
▪ Maar er zijn ook mengvormen, ongeveer 10%
o IBD is NOT IBS (irritable bowel syndrome)
▪ IBS is vooral bij mensen van middelbare leeftijd
▪ Vaak zonder dat er iets gevonden wordt.
o Incidence of IBD has significantly increased over time in the US
o An estimated 1.6-3.1 million are living with Crohn’s or ulcerative colitis in the US

• Epidemiology
o The peak age of onset of UC and CD is between 15 and 30 years old.
o A second peak occurs between the ages of 60 and 80

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• Comparison of UC and CD (zie foto)
o 10% does not fit into either group and are deemed
indeterminate colitis

• Clinical features
o Ulcerative colitis
▪ Start in het rectum en tast een deel van de
darm aan
▪ Colon only
▪ Rectal involvement
▪ Mucosal disease
▪ Diffuse ulceration (uitstulpingen),
granularity friability, bleeding, exudate
▪ No fistulas of granulomas
o Crohn’s disease
▪ Any segment
▪ Rectal sparing
▪ Skip lesions
▪ Transmural
▪ Aphthous ulcers, serpiginous ulcers, cobble
stoning
▪ Fistulae
▪ Granulomas

• Symptoms (heel moeilijk om op basis van de symptomen

alleen een onderscheid te maken tussen CD en UC!)
o Ulcerative colitis
▪ Predominant symptoms
- Rectal bleeding (onderste deel van maagdarmkanaal)
- Frequent, small volume, loose stools
- Mucous discharge from the rectum
- Tenesmus, urgency, rectal pain, abdominal pain
▪ Other symptoms
- Altered bowel movements
❖ Increased stool frequency
❖ Decreased stool consistency
- Abdominal pain
❖ LLQ cramping, relieved with defecation
❖ Tenesmus (neiging voelen om stoelgang te maken)
- Haematochezia (blood in stool)
o Crohn’s disease
▪ Altered bowel movements
- Chronic or nocturnal diarrhoea (geen controle hebben)
▪ Abdominal pain
- Postprandial RLD abdominal pain
- Distension
▪ Weight loss
▪ Fever

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• Pathogenesis of IBD (see picture)
o Genetics
o Environment, bv. stress
o Immunology
o Microbiome
o Mensen die geen appendix meer hebben, heb je veel minder
kans op het ontwikkelen van UC!

• Pathophysiology: schematische voorstelling

• Complications

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• Hoe diagnose stellen?

• Management
o The goal of the treatment is to
▪ Improve and maintain patient’s general well-being
▪ Treat acute disease
- Eliminate symptoms and minimize side effects and long-term
adverse effects
- Reduce intestinal inflammation and if possible heal the mucosa
▪ Prevent complications, hospitalisation and surgery
▪ Maintain good nutritional status
o The approach to treatment must be tailored to the individual. Factors that determine
the approach to treatment include
▪ Disease severity
▪ Anatomic location of the disease
▪ Previous response to medication
▪ Side effects of medication
▪ Co-morbidities (other diseases or medical conditions that the person has)

• Medicatie die kunnen helpen (niet vanbuiten kennen, maar principe erachter wel
o Eerst minder zware medicatie geven, als dat niet helpt overschakelen naar een hoger
niveau en dus zwaardere medicatie geven.

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23. Clinical topic 5: Mucoviscidosis / Cystic Fibrosis
• Clinical case
o Guus is nu 4 jaar en werd geboren na een normale zwangerschap. De eerste dagen
na geboorte kon hij geen stoelgang maken.
o In de eerste 3 levensjaren heeft hij 3x een longontsteking doorgemaakt en moest
daarvoor al 2 x opgenomen worden in het ziekenhuis voor intraveneuze antibiotica.
o Hij komt ook niet goed bij in gewicht. Percentiel voor G en L is <P3. Hij heeft ook
altijd een soort vettige stoelgang.
o Kinderarts vermoedt ‘mucoviscidose’ en laat een genetische test uitvoeren. Deze
toont een mutatie in het CFTR gen.

• Cystic fibrosis (CF) = mucoviscidosis

o Autosomal recessive disease
▪ Vader en moeder zijn drager, en geven allebei het
verkeerde allel door.
o Mutation in the CFTR gene: codes for an epithelial chloride
channel
o Dysfunction/absence of the CFTR channel
o > 1000 different mutations
o Incidence 1/4000
o Process (hoe ontwikkelt het zich?)
▪ Disturbed transport of water and electrolytes

▪ Abnormal viscosity of all exocrine secretions

▪ Multi-organ disease
- CF gaat bijna alle organen aantasten
o Consequences, dus welke organen het kan aantasten en de gevolgen daarvan
▪ Lung
- Sinusitis/nasal polyps
- Bronchial infections
▪ Pancreas
- Exocrine PI (85-90%)
- Endocrine PI
▪ Liver/gut
- Liver fibrosis
- Meconium ileus
- Constipation, maar ook diarree
▪ Other
- Salt loss in sweat (verhoogd gehalte aan zout in het zweet)
- Male infertility
o Eerste ziektetekens
▪ Chronische of herhaalde luchtweginfectie 50%
▪ Gewichtstagnatie 40%
▪ Veel wenen en altijd honger
▪ Vette diarree 30%
▪ Meconium ileus bij geboorte 10%
▪ Tekens van malabsorptie: oedeem, anemie, hematomen, ... <5%

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 ▪ Neuspoliepen, verlengde geelzucht, uitdroging, invaginatie, atypische
appendicitis, levercirrose, rectumprolaps, steriliteit, … <5%
▪ Er zijn ook mannen die het hebben, maar hier niet zo veel van ervaren en er
pas achter komen als ze merken dat ze niet vruchtbaar zijn.
o Diagnose
▪ New-born screening
- Flanders since jan 2019
- Wallonie since jan 2020
▪ Based on symptoms
- Sweat test
❖ Raised sweat chloride concentration
- Genetic diagnosis
❖ 2 disease causing mutations
o Overlevingskans is toegenomen
▪ Door betere therapieën
▪ Door vroegere diagnoses
- Maar vaak leven ze niet zo lang.

• Pancreas
o Exocrine = digestion (pancreas helpt bij vertering)
▪ Bij CF: progressive fibrosis of the pancreas leading to pancreatic dysfunction
▪ Treatment:
- Pancreatic enzyme supplements with every meal (Creon)
❖ Vervangt de normale enzyme
- Calory rich, fat rich meals
- Vitamin supplements ADEK
o Endocrine: CF related diabetes

• Diabetes Mellitus als gevolg

o Verlies van functie van de insuline
producerende cellen ter hoogte van de pancreas
(thv ‘eilandjes van Langerhans’).
o Minder insuline
▪ Geen verwerking van glucose leidt tot
hyperglycemie (= te veel glucose)
▪ Insuline ook belangrijk voor andere
stofwisselingsprocessen
o 2 soorten van diabetes
▪ Type 1 Noord-Europa  , insuline
dependent 2/1000
- Vooral bij kinderen
- Is niet te genezen
▪ Type 2 (Extreme) obesitas
- Vooral bij volwassen personen
- Niet altijd insulineafhankelijk
o Leeftijd zz < 1 jaar
▪ Piek - 12-13 jaar

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 o Korte symptoomperiode: polyurie, polydipsie, G-verlies, secundaire enuresis (=
opnieuw bedplassen)
o Diabetische keto acidose
▪ Dehydratie
▪ Acidose – diepe AH (DD pneumonie)
▪ Buikpijn (leidt soms tot verkeerde diagnose van appendicitis)
▪ Hypovolemische shock, suf, coma
o Diagnose
▪ Glycemie, >180mg/dL
▪ Glucosurie, ketonurie
- Vinden we in onze urine
o Chronische behandeling
▪ Diabetes team
- Multidisciplinair
- Teaching ++++
- Insuline en dieet (cave
hypo en hyperglycemie)
- Extra aandacht bij
ziekte: voorkom ketose
- Monitoring +++
- Normale groei en ontwikkeling
- Preventie van lange termijn verwikkelingen

• Nose and sinusses

o Viscous secretions and chronic nasal obstruction
o Nasal polyps
o Pansinusitis
o Treatment
▪ Nasal steroids
▪ Nasal lavage
▪ Endoscopic sinus surgery

• Lung (hier zit vooral het grootste probleem van CF)

o Chronic/recurrent infections
▪ S aureus, H influenzae and Pseudomonas aeruginosa
▪ Obstructive lung disease and progressive lung destruction and bronchiectasis
o Early and aggressive treatment of infections
▪ Antibiotics
▪ Inhaled therapy: Pulmozyme, Hypertonic saline
▪ Daily intensive ‘airway clearance’
o End stage lung disease
▪ BiPAP, lung transplantation

• CF patient follow-up
o Clinical FU
o Spirometry: kijken hoeveel lucht u kan inademen en hoe snel terug uitademen
o X ray/ CT scan
o Sputum cultures

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 • Possible therapies
o Gene replacement o Mucolytic drugs
o Protein replacement o Mucous clearance techniques
o Gene read through therapy o Antimicrobials
o Ion channel modulations o Anti-inflammatory agents
o Restore airway surface liquid o Lung transplant
Belang van neonatale screening: als je het tijdig opspoort, kan je het ook beter aanpakken en zijn
overlevingskansen groter!

• Chest physio in CF
o Conventional chest physiotherapy
▪ Postural drainage; percussion; chest shaking; huffing; and directed coughing.
o Positive expiratory pressure (PEP) mask therapy
▪ PEP is defined as breathing with a positive expiratory pressure of 10 to 25
cmH20.
o High pressure PEP (hPEP) mask therapy
▪ It is a modification of the above PEP technique but includes a full forced
expiration against a fixed mechanical resistance.
o Active cycle of breathing techniques (ACBT)
▪ This includes relaxation or breathing control, forced expiration technique
(FET), thoracic expansion exercises and may include postural drainage or
chest clapping.
o Autogenic Drainage (AD)
▪ As described originally by Chevalier or modified versions thereof.
o Exercise
▪ With the sole purpose of improving mucus clearance as the primary
intervention, with or without additional techniques.
o Oscillating devices
▪ Flutter or cornet, thoracic oscillation, and oral oscillation

• The chest physiotherapist in CF

o ‘Airway clearance’
o Inhalation therapy (nebs, puffs, dry powder inhaler)
▪ Technique
▪ Adherence
o Sputum induction
o Physical training/exercise
▪ Also post transplant
o Non invasive ventilation
o Nasal lavage
o Non –respiratory: muscolosceletal pain, pelvic floor muscle training (incontinence)

• Conclusion: Cystic fibrosis

o Severe and life shortening disease
o Morbidity mainly secondary to respiratory disease
o Airway clearance has a central role
o The advent of new CFTR modulators will change the face of CF in the near future

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24. Clinical topic 6: Tuberous sclerosis complex (TSC)
• Clinical case
o Joran is 3 year old boy and already has a complicated medical history.
o He was born at term without any problems.
o Around the age of 6 months he developed ‘epileptic spasms’ and was hospitalized for
14 days to stop the seizures with anti-seizure medication (vigabatrine).
o At that time the physician noted white depigmentation spots on the trunk and he
suspected the diagnosis of TSC. This was confirmed with genetic testing (TSC2).
o At the age of 2 years, he developed other types of seizures for which he needs anti-
seizure medication. Seizures are now less frequent but still present.
o For the parents, the most difficult problem is that they already notice that he has a
severe developmental delay and some autistic traits.
o On a recent MRI scan of the brain a small tumour is seen in the wall of the ventricle.
This will be treated with one of the new drugs for TSC: everolimus.

• TSC
o Werd voor de eerste keer beschreven door dhr.
Bourneville (lang geleden)
o Het is een multisysteem aandoening, dus kan in alle
organen voorkomen
▪ Maar komt vooral in de hersenen voor:
verschillende verdikkingen die er niet horen
te zijn
o Oorzaak
▪ Genetische oorzaak
- Autosomaal dominante aandoening:
als een van de twee ouders de ziekte
heeft, en die geeft het door aan het
kind, dan heeft het kind 50% kans op
het aanmaken van die ziekte
❖ Het kan zeer minimaal
aanwezig zijn bij de ouders,
maar toch grote gevolgen
hebben voor het kind
➢ Ouders zijn zich hier
niet bewust van,
raken zwanger en
het kind draagt er
dan grote gevolgen
van.
❖ Dit is eerder uitzonderlijk
- Meestal ontstaat het na de bevruchting (dus beide ouders zijn geen
dragers) door een mutatie op een bepaald gen.
- Bij een aantal kinderen is er geen mutatie te vinden en hebben ze de
ziekte toch (10-15%)
▪ Op de foto zie je hoe de ziekte zich dan ontwikkeling

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 o Ontwikkeling
▪ Er zijn twee cellen die de mTOR
pathway gaan inhibiteren, en als dat
gebeurt dan ontstaan er verkeerde
celgroei.
- Dit kan leiden tot zowel goed-
als kwaadaardige tumoren (op
allemaal verschillende
plaatsen)
- Dat wil dus eigenlijk zeggen dat
die mTOR pathway er normaal
voor zorgt dat er geen tumoren
kunnen ontstaan.
o We noemen het een neuro-cutane ziekte: het
doet zich vooral voor in de hersenen (neuro) en
in de huid (cutaan).

• TSC in onze hersenen

o Het loopt op alle gebieden verkeerd in de hersenen
▪ Cellen zien er verkeerd uit, er zijn veel te veel cellen, de cellen zijn niet zo
mooi uitgebouwd, er is veel verkeerd met de synapsen.
o Als je dat allemaal bekijkt, is het niet onlogisch dat de patiënt neurologische
problemen heeft
▪ Zoals epilepsie, gedragsproblemen (autisme), …

• Symptomen (zie foto)

o Kan van de ene patiënt tot de andere patiënt
variëren!
▪ Sommige hebben helemaal geen last,
andere hebben heel veel last!
o Als je voor de geboorte de diagnose kan stellen,
en je beseft dat de outcome niet goed is, dan
zijn er veel ouders die ervoor kiezen om de
zwangerschap te beëindigen.
▪ Dit is een moeilijke discussie, want
sommige ervaren hier helemaal niets
van
o Als de kinderen geboren worden en we hebben
de prenatale diagnose kunnen stellen, dan kunnen we heel snel tot behandeling
overgaan
▪ We kunnen dan persoonlijke behandeling/medicatie toepassen en dan is de
outcome veel positiever!

• Uitingen van TSC (afhankelijk van patiënt tot patiënt)

o Bolletjes op het lichaam (gelaat, lijkt op acne, maar is het niet)
o Pigmentvlekken (waar geen pigment is, dus witte vlekken)
o Gezwellen op het tandvlees, de nagels, in de hersenen, …
o Ook ter hoogte van de nieren angiomyoliopolen (AML)

165
• Diagnose
o We stellen de diagnose steeds vroeger!
▪ De meeste diagnoses worden gesteld voor het eerste levensjaar
o Er zit een soort systematiek in
▪ Cardio-problemen verdwijnen meer en meer (er ontstaat een tumor, maar
gaat ook weer weg)
▪ Longproblemen komen op latere leeftijd
▪ Huidproblemen komen op latere leeftijd
▪ Hersenproblemen ontstaan vaak op vroegere leeftijd
o We zien dat er voor de verschillende problemen een soort leeftijdsvoorkeur is
▪ Sommige problemen ontstaan al zeer vroeg, andere komen pas op latere
leeftijd naar boven, terwijl de mutatie al aanwezig is vanaf de geboorte

• Epilepsy in TSC
o Epilepsy in up to 90% of patients with TSC
o 71% of pts develop seizures in the first 2 years of life
▪ Ontstaat dus zeer vroeg
▪ Hoe vroeger epilepsie ontstaat, hoe ernstiger de impact op de rest van de
ontwikkeling
o Known genetic defect and disordered pathway (mTOR) = oorzaak
o Known morphological substrate of epilepsy (cortical tubers)
o Significant epileptic co-morbidities (speech delay, intellectual disability, autistic
behaviour)
o Possible prenatal diagnosis
▪ Maakt mogelijk dat we epilepsie sneller herkennen en erkennen en dus ook
kunnen behandelen, wat zal leiden tot hopelijk een betere outcome
o Hoe komt het tot uiting)
▪ Epileptische spasmes (knikken, lichaam trekt bijeen)
- Hier kunnen we een medicatie voor geven
▪ Focale epilepsie (kortdurend, trekkingen rond gezicht, armen, …)
- De eerste medicatie werkt hier niet goed bij, en daarbovenop is
epilepsie bij TSC patiënten heel
moeilijk te behandelen
❖ Als we medicatie geven aan
gewone epilepsiepatiënten,
dan stopt de epilepsie, terwijl
bij TSC patiënten dat
helemaal niet zo is.
▪ Symptomatische algemene epilepsie
- Zeer ernstige vorm van epilepsie,
waarvoor we bang zijn dat de patiënt
daar verder naar ontwikkelt
o Blijf onthouden dat de ontwikkeling van het ene kind niet samenhangt met de
ontwikkeling van het ander kind!
▪ We zien wel patronen, maar het kan helemaal anders verlopen.
▪ Het is dus niet te voorspellen!

166
• Common cognitive problems

• Common behavioural problems

167