Pathology Aantekeningen Deeltentamen 1
Week 1 Chapter 2 (Cell injury, cell death and adaptations)
What is disease?
A disease is the dysfunction of an organ or tissue as a result of damage to the cells.
- The damage can be caused by chemical, radiation, microbacterial and DNA damage for example
- The damaging agent is the etiology. The influence on and the changes in cellular processes reflect
on the pathogenesis.
What is normal?
In the first shown slide, the etiology is radiation.
- The radiation causes DNA damage, which results in the pathogenesis (the replacement of a single
nucleotide).
On the second slide, the etiology is cholera.
- The bacteria Cholera produces a toxin that influences the cell by increasing chloride ion secretion.
With this secretion, water comes along and this leads to water leaking out of the cell (this causes
diarrhea which can be fatal).
Normal relates to the most frequent state in a population defined by factors such as age distribution,
gender, et cetera.
Dictyostelium discoideum is a amoebe that can survive during food shortage by organizing itself in a
multicellular aggregate.
Cell damage, stress & stressors
Disease is caused by damage to (a part of) a cell or group of cells (etiology).
- The initial damage can cause further damage (pathogenesis)
- The cell/organ reacts to the damage by minimizing the impact of it (adaption)
Slide 14: Heart cells cannot divide, so if there is an increased load of the heart has to pump
through the body (high blood pressure), hypertrophy will be the result (the cells of the heart
cells are becoming bigger). This is an example of adaptation.
Slide 14: However, if the heart cell does not receive any oxygen anymore, the heart cell will
die. This will cause cell death (route B).
- Damage can be reversible as it leads to adaptation or, ultimately, the death of the cell
Slide 15 hoef je niet helemaal te kennen qua alle stoffen en dergelijke.
Cell and tissue adaption
Apart from hypertrophy, hyperplasia can also occur. This refers to the increase in the number of cells
(not in the size of cells!).
The third form of adaption is atrophy. This refers to the decrease of tissue by decrease of cell size
and/or number.
- Atrophy occurs through proteasomal degradation, autophagy and apoptosis (see slide 19).
The fourth form of adaption is metaplasia. This refers to the replacement of one tissue by a (normal)
other tissue.
Cell and tissue death
The first form of cell/tissue death is oxygen shortage.
- The cell needs energy to upkeep an optimal internal environment. This is guaranteed by having
high concentration of sodium ions outside the cell and a high concentration of potassium ions
inside the cell. This phenomenon is realized by the Na+-K+-ATPase pumps. When there is a lack of
oxygen, all the sodium ions will come into the cell while all the potassium ions will migrate
outside. This causes the cell to swell, and if it continues to do so, the cell will die.
- The process of the swelling is reversible to some extent: if there is an oxygen flow to the cells that
occurs on time, the pumps will start working again and the cell will return to normal.
Cell damage: necrosis and apoptosis
, Slide 23 gewoon leren.
Necrosis versus apoptosis: the essential differences
The biggest difference between apoptosis and necrosis is that necrosis causes an inflammatory
response and apoptosis does not.
- Necrosis induces repair and defense, but also the formation of scar tissue.
Het groene lijstje gewoon leren.
Caseous necrosis (TBC) looks like French cheese.
- This type of necrosis solely occurs in tuberculosis patients.
Fat necrosis (in pancreatitis) can occur when the pancreas gets damaged. The pancreas contains
lipases that will cause harm to the surrounding fat tissues when released due to damage. This leads to
depositions of calcium salts (the white spots are depositions of calcium salts, lung fatty acids. Overall it
is dead tissue).
Fibrinoid necrosis occurs in the arterial wall when it is inflamed. This type of necrosis causes the cells
in the blood vessel walls to disappear due to necrosis. The structure of this phenomenon resembles
fibrin, hence the name.
Regulated elimination and replacement
These are examples of natural processes in the body where apoptosis plays a role in the physiology. In
comparison to apoptosis, necrosis never has a physiological function.
When does apoptosis occur?
Lijstje gewoon leren.
Extrinsic apoptosis-induction
The extrinsic apoptosis pathway is induced when a lethal signal from outside the cell (FasL, TNF)
triggers, through the activation of a receptor, a cascade that leads to apoptosis.
- The activation through a Fas/FasL binding often occurs in virus infected cells where the T cells are
FasL positive.
Dia uit je hoofd leren.
Mitochondrial (intrinsic) pathway
The intrinsic mitochondrial apoptosis pathway is induced when there is a lack of survival signals or
damage/stress to the cell itself leads to apoptosis.
- The mitochondria consist of BCL-2 or BCL-XL (or BAX) that can form complexes … ???
- BCL-2 is anti-apoptopic. In B-cell (follicular) lymphoma there is a loss of a apoptosis response
because the BCL2 gene is overexpressed.
- Dia 37 en 38 gewoon leren.
Dia uit je hoofd leren.
Unfolded protein response: ER stress
This slide shows that a certain amount of misfolded proteins won’t necessarily cause apoptosis of the
cell (it will ensure a reduced load of misfolded proteins instead). However, if the amount of misfolded
proteins exceeds a boundary, the cell will be forced to go into apoptosis.
DNA breakdown in apoptosis
Caspase 3 and 6 specifically cut into 32 basepair fragments and this will cause a ladder as shown on the
left figure. If you see this ladder, you know that the DNA went into apoptosis. This is a way to see if a
cell underwent apoptosis or not.
Phsophatidylserine
, Another way of researching the occurrence of apoptosis is by looking at the phospholipid bilayer of the
cell. This bilayer contains phosphatidylserine and is normally placed on the inside of the cell.
However, if the cell is going into apoptosis, this phosphatidylserine will flip around to the other side (so
towards the outside of the cell). When you add a fluorescent dye, it will bind to the phosphatidylserine
and the green dots on the slide present apoptopic bodies (the aforementioned binding).
Another form of dealing with cell stressors: storage of the molecules
If there is a small amount of cell stressors, these molecules can be storaged by the cell through an
intracellular or an extracellular manner.
- People eat too much fat can have a storage of fat (triglyceride) in the liver cell. The result of this is
named fatty liver.
- It is also possible that there is a lack of a certain enzyme that will inhibit the metabolization of a
substrate and therefore it will be accumulated inside the cell. However, if the cell dies, all these
substrates will be released again and this whole process will be repeated.
Dystrophic calcification
On slide 46, all the white spots represent calcification (deposits of calcium).
The ultimate cell damage: cellular aging
Gewoon leren.
Eponyms
Eponyms are diseases that are named after the person who discovered it. There has been a lot of
controversy regarding whether this is okay or not, because it is being said that it is better to name
diseases after their genetic background.
