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Pathology Summary
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CELL INJURY, CELL DEATH,ADAPTATIONS
Etiology and pathogenesis of diseases
A disease is a dysfunction of an organ or tissue, because of damage to the cells. The damage can be of
many causes, such as chemical, thermal, radiation, DNA damage, micro bacterial, etc. The damaging
agent is the etiology and the influence on and the changes in cellular processes reflect the pathogenesis.
One change can have a major effect. For example the substitution of proline instead of histidine. Proline
kinks the chain of proteins, which leads to a structural change in the protein. This protein is called a
pathogenic protein, because it underwent change. Sickle cell anaemia is a mutation in DNA coding for
haemoglobin and is about 1 base pair that is changed. Because of the changed base pair, the red blood
cell will crystalize at low oxygen levels. Nice round blood cells will become sickle shaped, cluster and
cause blockage of cells.
The etiology of cholera is a bacterium, which can lead to enormous diarrhoea, because the bacterium
produces a toxin that damages the gut cells and loads of water are lost. Since cells can’t keep the water
inside, lots of people suffer from dehydration. In this case, the pathogenesis is the toxin made by the
bacteria.
Communities of cells
Cells are rarely alone, they are shaped and grouped together to form communities. A person is a
community of cells. Sometimes these communities can arise if matter dictates things. Conditions of
amoeba are unfavourable, so they will aggregate. Cooperation is vital to survive.
Multicellularity is a coping mechanism, but also gives problems. A good internal milieu attracts intruders,
so defence mechanisms are needed. Bacteria and viruses want to enter cells for their good internal
milieu. Also, there needs to be an organisation and a clear division of tasks. Close control on proliferation
is needed desperately for some cells (blood cells) and others don’t need to be proliferated (brain cells,
because no more space in skull). Proliferation needs to be tightly controlled, because when something
goes wrong, cancer will arise. Specialization is also necessary, not all cells can perform all tasks.
,Stress and stressors
A disease is caused by damage to cells (or parts of or groups). This is the etiology of the disease. Initial
damage can cause further damage, also to other cells. The organism or cell will react in order to minimize
the damage or repair it. Sometimes, this causes change in an organ or a group of cells, which is called
adaptation. When adaptation is not possible, it will lead to cell death. One cell dying is not a problem,
but loads of cells dying is.
Adapted myocyte Normal myocyte Death myocyte
When the blood pressure is high, the heart needs to do more work and the heart will adapt with making
the cells bigger and the heart will become bigger as well. This is known as hypertrophy of the heart.
However, these bigger cells need more oxygen, so there is a chance of additional damage because there
is no sufficient oxygen supply. When the heart cell is insufficiently equipped to less oxygen, it will die.
Heart cells can’t divide, so they are lost. When too much cells die, this can lead to a myocardial
infarction. The dead cells will become a scar if the patient is able to survive.
• Hypertrophy is the increase in size of cells, but not in number of cells. This is because muscle
cells can’t divide and have to become bigger to cope with change (for example the uterus after
pregnancy).
• Myocardial hypertrophy is caused by an increased workload. This can result in mechanical
stretch, because the blood pressure rises. It can also be caused by drugs or growth factors. All
the proteins in the heart that are involved in contraction need to increase in number to increase
the workload.
• Hyperplasia is another way to cope with change. It is an increase in the number of cells, not in
the size of them. For example in the breast, during pregnancy, which is important for lactation.
• Tissue can also adapt by becoming smaller. This is atrophy, which is a decrease in cell size and/or
number of cells. Atrophy usually happens by apoptosis (programmed cell death). Parts of cells
can also be taken out, which happens by autophagy. This is when cells takes out parts of itself,
without killing itself. Therefore, the cells shrinks and the tissue gets smaller. Another way of
destroying cell components is proteasomal degradation, which also cleans up garbage and
makes the cell smaller.
• Metaplasia is the replacement of one tissue by another
tissue, which should be normal. This happens in airways
with people that smoke. The smoke is hot and contains
toxic chemicals, while the cell line in normal airways is
only 1 layer thick respiratory epithelium with cilia on top. The cell remodulates to get multi-
layered (squamous) epithelium, to protect from the hot smoke, but this doesn’t contain cilia.
When keeping on smoking, squamous epithelium will become normal, and can even become
cancerous.
One of the major reasons for cells to die or be damaged is by lack of oxygen. This causes swelling of cells,
because energy is needed to pump out water and oxygen is needed for energy. This lack of energy causes
failure of pumps, such as Na+-K+-ATPase. Because there is lots of water in cells, cells will blow up.
Necrosis and apoptosis
Supplying oxygen can solve the oxygen deprivation, when it hasn’t been going on for too long. Some cells
are quickly damaged by oxygen loss, for example, oxygen deprivation in the brain and heart is
irreversible after 5 minutes. Other cells can withstand this for a longer period of time. There are 2 ways of
dying in cellular pathology, which are necrosis and apoptosis. Necrosis is always caused by a trigger from
the outside (usually oxygen deprivation) and apoptosis is usually triggered by the inside of the cell
(suicide).
, Necrosis Apoptosis
Necrosis always causes inflammation as a reaction. This inflammatory response induces repair, no such
thing happens in apoptosis. Here, the cell disintegrates in little fragments. The inside of the cell is not
exposed to the surrounding and there will be no inflammation induced. Apoptosis can be part of the
physiology, for example the development of the hands starts as a clump and the area between the
fingers will be removed via apoptosis. Necrosis is never physiological, always pathological. Apoptosis is a
strictly regulated process in which the cell decides to end its life. This doesn’t happen in necrosis, because
this is induced from the outside. There are different types of necrosis:
• Coagulation necrosis → Is characterized by the formation of a gelatinous substance in dead
tissues in which the architecture of the tissue is maintained, but there are no living cells.
• Colliquative necrosis → Will make an area disappear and a big hole will be left. This is common
in the brain.
• Caseous necrosis → Is a combination of coagulative and colliquative necrosis. The necrotic tissue
appears as white and friable, like clumped cheese.
• Fat necrosis → Happens in fatty tissue and is caused by chemical compounds that are released
from fatty tissue, which are highly irritative.
• Fibrinoid necrosis → Caused by vascular damage and is marked by complexes deposited within
arterial walls, together with fibrin.
Apoptosis happens during a lot of different processes in the human body, with different purposes:
1. Embryonal development, because there is a massive overproduction of cells
2. To get rid of virus-infected cells
3. To stop an inflammatory response
4. For normal tissue homeostasis
5. Selection of early maturational stages of lymphocytes by antigen receptors
6. Involution or atrophy
7. Elimination of stressed cells by natural killer
cells (NK-cells)
8. Elimination of damaged cells
Apoptosis can happen via the intrinsic pathway, that
is regulated by a family of proteins, from which BCL-2
is anti-apoptotic and BAX is pro-apoptotic. These
proteins usually balance each other out, but this
balance can shift via regulation. Once apoptosis wins,
a cascade will activate caspases, which cut everything
, in cells. Apoptosis can also happen via the extrinsic pathway, which is triggered by
factors from the outside. The Fas receptor is located on the cell membrane and once
another cell with Fas-ligand binds to it, the same cascade of caspases will be
activated inside the cell.
Tumours of lymph nodes are called lymphoma’s. One of the most prevalent tumours
is follicular lymphoma. In this case, BCL-2 is upregulated, because it is translocated
into the genome and becomes under the influence of the heavy chain of the
immunoglobulin genes. B-cells use these very frequently. So, the BCL-2 gene will be
transcribed much more, which will lead to overexpression. Therefore, cells no longer undergo apoptosis
and keep stacking up. This causes the tumour to grow.
Cytochrome C forms an apoptosome, which is the body that performs apoptosis. This body activates
caspases and sets of the apoptotic process by activating caspase-9. Cytochrome C binds to APAF-1, which
is apoptosis-activating factor-1. The thus formed heptamer complex binds procaspase-9 and ATP.
Procaspase-9 is activated and the cascade of caspase-activations follows. Executioner caspases (3 and 6)
cut in the DNA in a reproducible manner. They do it in small bits of 32 base pairs. The cutting in 32 base
pairs results in a DNA ladder.
In the normal situation, there is phosphatidylserine, which is bound to the cell membrane at the inside of
the cell. In apoptosis, it goes to external side of cell. This causes the cell to be recognized by other cells.
This also helps for researchers to determine which cells undergo apoptosis, because phosphatidylserine
can bind annexin V, which is a fluorescent die. This binding only happens when phosphatidylserine is
located on the outside of the cell.
Necroptosis is no necrosis and no apoptosis, it is a programmed form of necrosis. There is a little
inflammatory response. Is not as bad as necrosis, but worse than apoptosis.
Storage of molecules
Another way to deal with stressors is the storage of molecules. When cells can’t deal with proteins, they
can take them up and store them. Sometimes, these proteins comes from the inside of the cell, for
example with an enzyme defect in cell, that can be caused by a DNA effect. When these proteins can’t be
broken down or only in the wrong way that results in abnormal proteins or lipids, they are stored in the
cell. One of the most frequent genetic diseases in men is the accumulation of iron in cells. These cells die,
because iron is toxic in large amounts.
Some tissue are marked damaged, because they accumulate calcium. Calcium is deposited in abnormal
tissue, which stiffens the tissue, for example in the aortic valve. It is a way to mark abnormal tissue. For
example, atherosclerosis, which is caused by exposure to too much fat. Calcium can also be deposited in
tumorous tissue. This is used to diagnose the tumour.
The ultimate cell damage is caused by aging. One of the factors that causes people to age is shortening of
telomeres. The ends of chromosomes are the telomeres. When cells divide, they replicate DNA, which is
evenly divided over both daughter cells. During division, the telomere shortens, so after each division, the
telomere becomes shorter. After so much divisions, the telomere will be gone. A short telomere region
induces a DNA damage response, which leads to an irreversible proliferation stop, called the cellular
senescence. Forced proliferation in the presence of short telomeres can lead to end-to-end joining of
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