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, Index
Index 2
Chapter 2. Cell injury, cell death and adaptations 3
Chapter 3. Inflammation and repair 6
Chapter 4. Hemodynamic disorders, thromboembolism and shock 10
Chapter 5. Diseases of the immune system 14
Chapter 5. Transplant rejection 20
Chapter 6. Neoplasia 24
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,Chapter 2. Cell injury, cell death and adaptations
What is a disease?
-Disfunction of an organ or a tissue because of damage to the cell.
The damage can be of many causes: chemical, thermal, radiation, DNA damage,
microbacterial etc. The damaging agent is the etiology, take for instance radiation which may
lead to a missense mutation. The influence on and the changes in cellular processes reflect the
pathogenesis, which is often a sequence. Sikkel cell anemia is a great example -> mutation.
Etiology vs pathogenesis (in dutch): etiologie beschrijft dus de oorzakelijke reden van de ziekte,
terwijl de pathogenese de fysiologische veranderingen beschrijft als gevolg van die ziekte.
Virchow -> the man who laid the foundation
for everything in pathology.
Multicellular individuals: a niche in nature,
with its own possibilities, but also its
problems:
-Internal milieu is optimized, and thus also
attractive for intruders. Effective defence is
required. INFECTIOUS DISEASES.
-Organisation and clear division of tasks is
mandatory, incl discipline of cells, a.o with
regards to proliferation. CANCER.
Cell damage, stress and stressors
-Disease is caused by damage to (part of) a cell or group of cells (etiology).
-The initial damage can cause further damage (pathogenesis).
-The cell/organ reacts to minimize impact of damage (adaptation)
-Damage can be reversible, lead to adaptation or, ultimately to death of the cell.
Adaption versus cell death -> higher workload -> hypertrophy. Also the organ will grow bigger.
If the stressor is permanent and to much for the cell to bear, it will die -> cell death.
• Hypertrophy -> increase in the size of cells, NO increase in number of cells!
• Myocardial hypertrophy -> mechanical stretch = increased work load.
• Hyperplasia -> increase in the number of cells (NOT in the size of cells)
• Atrophy -> decrease of tissue by decrease of cell size and/or cell number. There
are different types of atrophy:
1. Proteasomal degradation: a protein will be degraded in peptide fragments by a
proteasome.
2. Autophagy: a membrane forms around the part to be broken down. A lysosome
fuses with the membrane and degradation takes place.
3. Apoptosis: programmed cell death.
• Metaplasia -> replacement of one tissue by a (normal) other tissue.
Cell damage by oxygen shortage: the cell swells. See the picture below. Cause:
failure of Na+/K+-ATPase.
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, Cell damage, necrosis and apoptosis = irreversible.
• Necrosis -> inflammation -> further damage.
• Apoptosis -> cell disintegrate and shrinks.
Main differences between necrosis and apoptosis:
Necrosis Apoptosis
Induces repair and defence No induction of repair or specific defence
Cell contents are released extracellularly Cell contents are not released in surroundings
Cellular catastrophy’ no regulation Cellular suicide’, under strict regulation
Pathologic Part of normal physiology
Occurs now and then Occurs continuously
There are several ways of necrosis -> depends on the place/organ. For example, coagulation
necrosis, colliquative necrosis, caseous necrosis (TBC). Fat necrosis -> necrosis of fat cells (for
example in pancreatitis). Fibrinoïd necrosis (arterial wall).
When does apoptosis takes place?
-Embryonal development.
-Normal tissue homeostasis (cell death and formation of new cells).
-Selection of early maturational stages of lymphocytes by antigen receptors.
-Involution or atrophy.
-Termination of inflammatory response.
-Elimination of virus-infected cells.
-Elimination of stressed cells.
-Elimination of damaged cells.
Mitochondrial pathway and death receptor pathway (intrinsic vs extrinsic pathway)
Intrinsic: lack of survival signals, or damage or
stress of the cell itself, induces apoptosis.
Extrinsic: a lethal signal from outside the cell (FasL,
TNF) triggers, through receptor activation, a cascade
leads to apoptosis.
BCL-2 and B-cell (follicular) lymphoma:
-Loss of apoptosis-response by overexpression of
BCL2- gen. Cause: BCL2-gen is, by translocation,
brought under control of the promotor of the heavy
chain of the immunoglobulin.
In dutch: BCL-2 is een belangrijk eiwit die celdood
reguleert door apoptose te remmen of juist te
induceren. Je cel krijgt geen signaal voor apoptose
wanneer BCL-2 te veel aanwezig is, wat in bepaalde gevallen niet goed is!
Besides BCL-2, there is another important protein: Cytochrome C. The protein has two functions:
1. Electron transport in oxidative phosphorylation.
2. Induction of apoptosis.
The apoptosome activates Caspase-9.
Cytochrome C binds to Apaf-1 (apoptosis-activating factor-1). Then, the thus formed heptamere
complex binds procaspase-9 and ATP. In the end, procaspase-9 is activated and the cascade
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