Case uitwerking
BBS2002 Cradle to Grave Cases
- Instelling
- Maastricht University (UM)
Extensive cases for the Cradle to Grave course of BMS bachelor course.
[Meer zien]Voorbeeld 4 van de 127 pagina's
Voorbeeld 4 van de 127 pagina's
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Voorbeeld van de inhoud
Case 1 –1) Define the ability of Stem Cells; what are the different classes and what are their function?
Stem cells are biological cells that can differentiate into other cell types, and more importantly can
duplicate themselves to produce more of these stem cells and hence give raise to many more
differentiated cells; differentiated cells on their own however cannot renew themselves, hence these
stem cells are especially required during growth but also during tissue repair and renewal. For
mammals these stem cells can mainly be subdivided into Embryonic Stem Cells and Adult Stem Cells;
in the latter the stem cells are purely for tissue renewal, as where during embryonic development
the totipotent or omnipotent stem cells are actually required to generate new tissue.
Stem cells require two properties; 1) One being the self-renewal, in which the ability to go through
multiple cell division cycles while maintaining undifferentiated is of the utter most importance; 2)
The second one being the capacity to differentiate into an array of multiple different cells. This so-
called cell potency determines into how many different subtypes of cells the stem cell can
differentiate, in the adult human body mainly unipotent or multipotent stem cells are found, which
differentiate into one specific cell type or a rather small group of cell types respectively.
Self-Renewal
The self-renewal obligation can be acquired in mainly two
different mechanisms. Most likely the stem cells replicate
asymmetrically, in which one daughter cells maintains the
function of the stem cell, whereas the other acquires the
function of differentiation; in this way one stem cell can give rise
to many differentiated cells, and many equal stem cells. Within
stochastic differentiation on the other hand the stem cell
produces two daughter cells that differentiate into the required
ones, however the levels of stem cells need to be kept on track
by another stem cell that undergoes mitosis to produce the first
stem cell.
Potency
Potency specifies the potential of differentiation into a subset of differentiated cells, the range of this
array of cells however depends on the type of cells. The level of potency of stem cells can on average
be separated into five specific types.
- Totipotent stem cells are only found within the embryo until it forms the
blastocyst; totipotency allows the cells to differentiate into all cell types of
the human (embryonic) body, but additionally the totipotent stem cells
can also differentiate into the cells that will form the placenta (the outer
layer of the blastocyst).
- Pluripotent cells are the descendant of the totipotent stem cell, however
they cannot differentiate into placental cells anymore, but can still
differentiate into all possible cells of the human body; pluripotent cells as
such can differentiate into all cell types of the trilaminar disc.
- Multipotent stem cells are also found within the adult human body and
can differentiate fairly large array of related cells.
- Oligopotent cells are more specific than multipotent stem cells and can
differentiate into a smaller group of closely related cells.
- Unipotent stem cells can only differentiate into one single type of cells.
1
,The level of potency decreases over the life span of the embryo and during the early life of the infant,
at a certain point the level of potency for the cells will no longer decrease, but the rate of meiosis
and renewal will drop over time as well. The level of potency depends on the amount of DNA that is
methylated, or more general has epigenetic alterations that will be inherited onto daughter cells;
fully demethylated cells, that are encountered after fertilization, can differentiate into much more
cell types than stem cells that have certain parts of their genome methylated. The epigenetic
changes of the daughter cells will accumulated and hence the level of potency can only drop to a
lesser extent. Ageing however is not directly related to the decrease in potency of stem cells, but
much more to the mutations in DNA or to the general decrease of active stem cells; when the
amount of stem cells decrease also the rate/capacity of repair of tissue damage will decline.
A stem cell thus can replicate itself to give rise to two daughter stem cells, which can both
differentiate into a certain set of tissue cells, the range of this differentiation depends on the type of
stem cell and partially during what part of the development these stem cells can be found in the
human body; or stem cells can asymmetrically undergo mitosis to form a stem cell plus a cell that will
differentiate itself.
The somatic stem cells, which can differentiate into a fairly restricted set of cells, can be found in the
adult body, unlike the embryonic stem cells. There are multiple types of somatic stem cells in the
adults human body; as such the haematopoietic stem cells, that can differentiate into all types of
blood cells, but also intestinal stem cells that constantly have to provide a new array of cells that
protect the human body from the gastric acid or the pathogens that can be found in the food. Other
stem cells are olfactory stem cells, endothelial ones, mesenchymal and testicular stem cells.
To induce proliferation of stem cells
and differentiation of the stem
cells, or progenitors, into a specific
cell type, Growth Factors are
required; Growth factors bind to
the receptors of the cells and hence
alter the intracellular environment,
however also the cell growth
caused might induce different cell
type formations. Structure wise the
growth hormones are peptide-like
hormones; they can act on close
proximity tissues, but can also act
on more distant tissues by a
diffusible (endo-, para- and
autocrine) or non-diffusible (juxta-
or metacrine) manners, and
regulate a variety of cellular events
including cell migration, survival,
adhesion, proliferation and
differentiation.
In the human body some of these growth factors can also override the initial pluripotency of the
stem cells, hence allowing them to become much more versatile (I would take this is a rather rare
sight though?).
2
, 2) How do the lungs develop during pre-natal and post-natal development? (stem cells)
2.1) How do the lungs start working during the post-natal ‘shock’
Guyton 84 Marieb 800 – Chap 22
The pre-natal lung development can be subdivided into five stages;
1) During the Embryonic Stage (week 3-7/9) the
formation of the major airways occurs via the
bifurcation of the foregut into oesophagus and
trachea and primary lungs buds.
2) During the Pseudoglandular Stage (week 5-17)
the main terminal bronchioles are being formed,
however until the end of this stage no bronchial
regions, and definitely no alveoli are present.
3) In the Canalicular Stage (week 16-26) each
terminal bronchiole formed during the
pseudoglandular stage will divide into two or
more respiratory bronchioles, which on their
turn divide into between three and six alveolar
ducts.
4) During the Saccular or Terminal Sac Stage (week 26-36) primitive alveoli will form, of which some also will
form actual functioning alveoli, but many more alveoli will form after birth until adolescence, and capillaries
will be formed which establish the close contact between the external air and the internal blood, and allow for
the close distance between air exchange and produces the actual blood-air barrier. At this point of time also
the surfactant found within the lungs will be start being produced, in response to cortisol, however the lungs
are still almost entirely deflated, and the thickness of the cells founds within the lungs will harshly lower.
5) During the Alveolar Stage, which starts after birth, the major amounts of alveoli will be formed during the
secondary septation, highly increasing the surface for gas exchange and within a minute after birth the lungs
start inflating, although it might take up to two weeks to fully inflate the lungs.
These five steps cause two critical factors that are
important within the gas exchange in the infant lungs,
and of course in later stages; 1) The structural growth
and coincidental branching of the lung segments, next
to the actual bifurcation itself of course, and blood
vessels that create the extensive alveolar-capillary
network and the huge surface area for gas exchange,
and 2) The production of surfactant, which keeps the
alveoli open and allows easy lung expansion without
excessive effort.
Before birth the baby or foetus receives oxygen from
the mother herself, the oxygen from the mother’s
blood diffuses through the placenta into the infants
blood, as where the opposite story takes into account
the carbon dioxide waste exchange. The oxygen from
the mother could be pumped through the infants body
via the ductus arteriosus, hence mainly surpassing the
lungs as an organ; the lungs before birth are filled with
fluid and have a rather high resistance against the
blood flow, this forced the oxygen rich blood to pass
via the ductus arteriosus into the rest of the body.
3
, After birth however the first obstruction for the infants life is perfusing its body by oxygen acquired
by its own lungs (Foetal Breathing Movements also occur, but to a much lesser extent and are mainly
required to allow for normal development instead of actually being required to obtain the oxygen),
instead of the ever so convenient oxygen delivered via the placenta and maternal blood. Before and
during the birth the lungs are filled with lung fluid, which, even though it is in contact with the
amniotic cavity, is not essentially the same as the amniotic fluid. The shock in temperature change
and environmental change in general, causes the central nervous system to take action and forces a
sudden gasping breath. The additionally the asphyxiation caused by the decrease in CO2 removal via
the umbilical cord will initiate the breathing mechanism within the lung; even when the baby does
not start breathing within the first two seconds it will most likely start at one point or another, while
he/she becomes progressively more hypoxic and hypercapnic, eventually leading to a point where
the stimulus will be strong enough to force breathing (hopefully at least).
The fluid within the lungs is removed through the blood and lymph system (but to some extent also
removed via the mouth during the pressure within the vagina that clears up part of the lungs of the
lung fluid), and will be replaced by air; this alteration from fluid to air also harshly lowers the vascular
resistance against blood flow within the lungs and a vigorous blood circulation starts, additionally the
surface area of the gas exchange increases due to the loss of lung fluid. During these initial 30
seconds the pulmonary blood flows increases. In this time the
oxygen rich blood from the lungs will cause a constriction of
the umbilical arteries; in about three minutes the blood flow
originating from the placenta is nihil. The levels of oxygen
within the lungs allow for the diffusion of oxygen into the
blood, and of course carbon dioxide to diffuse from the blood
into the air within the lungs, the difference between resistance
before and after birth causes the blood to now mainly flow
through the lungs instead. This increase in pulmonary venous
return causes a slight increased left atrial pressure compared
to the right atrial pressure, this difference closes the foramen
ovale and allows it to grow together with the septum to fully
close the one-way valve. At this point in time the lungs also
produce bradykinin to shut off the ductus arteriosus (where it
functions as a vasoconstrictor! Unlike normally!), which
decreases the amount of oxygen poor blood that will be pumped into the aorta via the right
ventricle, and eventually will lead to the deterioration and eternal closure of the ductus arteriosus.
The decrease in fluid within the lungs finds place after birth, but can also already be initiated before
birth; hormonal changes within the female body for example will lower the fluid production and
might initiate the baby to start actively removing the fluid from the lungs. The raise in the PCO2 of the
baby’s blood also excites the respiratory centres, whilst the CO2 will build up without the active
removal, which up until then occurred via the placenta, and will cause the baby to start breathing.
The respiratory system comprises two branched structures: The respiratory tree and the adjacent
cardiopulmonary vasculature. The epithelium of the trachea and lungs derives from the anterior
foregut endoderm, which also gives rise to the oesophagus, liver and thyroid for example. The
bifurcation of this primitive tube will form the dorsal gut tube, more specifically the oesophagus
itself, as where the ventral lying bifurcated tube will give to the trachea and the entire epithelium of
the lungs itself. The mesenchymal components of the lungs on the other hand, such as the
vasculature, arise predominantly from a specialized region of lateral mesoderm contiguous with the
developing cardiac mesoderm.
4
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