Chapter 2 cell injury, cell death and adaptions
Pathology is the study of the causes and effects of disease or injury. The word pathology also refers
to the study of disease in general, incorporating a wide range of biology research fields and medical
practices. However, when used in the context of modern medical treatment, the term is often
referred to the diagnosis of diseases, mostly through analysis of organs, tissues, cells, and body
fluids.
A disease is any abnormality that causes loss of health and is characterized by a specific set of
features (signs, symptoms, functional and morphological manifestations). Usually, disfunction of an
organ or tissue occurs due to damage to the cells. The damage can be of many causes, chemical,
thermal, radiation, DNA damage, micro bacterial, etc. The damaging agent is the etiology (e.g.,
radiation), the influence on and the changes in cellular processes reflect the pathogenesis.
Multicellular individuals
The social amoeba Dictyostelium discoideum survives periods of food shortage by organizing itself in
a multicellular aggregate → multicellular by choice.
Multicellular individuals: are a niche in nature, with its own possibilities, but also its own problems:
- internal milieu is optimized, and thus also attractive for intruders. Effective defense is
required → Infectious diseases
- organization and clear division of tasks is mandatory, incl. discipline of cells, 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 (adaption)
- damage can be reversible, lead to adaption or, ultimately to cell death.
Cell- & tissue adaption
- hypertrophy: increase in the size of the cells, not an
increase of number
- hyperplasia: increase in the number of cells, not in
the size
- Atrophy: decrease of tissue by decrease of cell size
and/or number
- Metaplasia: replacement of one tissue by a (normal)
other tissue. The most common type of metaplasia is
metaplasia of glandular epithelium into stratified
squamous epithelium. Metaplasia occurs due to
reprogramming of tissue stem cells.
Pathology 1
,Cell death
Necrosis versus apoptosis: the essential difference
Necrosis Apoptosis
Pro-inflammatory Anti-inflammatory
Induces repair and defense No induction of repair or specific defense
Cell contents are released extracellularly Cell contents are not released in surroundings
‘Cellular catastrophe’, no regulation ‘Cellular suicide’, under strict regulation
pathologic Part of normal physiology
Occurs now and then Occurs continuously
→ protein degradation in living cells is due to proteasomal degradation or autophagy.
Types of necrosis:
- Coagulation necrosis: Coagulative necrosis is a type of accidental cell death typically caused
by ischemia or infarction. In coagulative necrosis, the architectures of dead tissue are
preserved for at least a couple of days.
- Colliquative necrosis: Liquefactive necrosis (or colliquative necrosis) is a type of necrosis
which results in a transformation of the tissue into a liquid viscous mass. Often it is
associated with focal bacterial or fungal infections and can also manifest as one of the
symptoms of an internal chemical burn.
- Caseous necrosis (TBC): When the hilar lymph node for instance is infected with tuberculosis
and leads to caseous necrosis, its gross appearance can be a cheesy tan to white, which is
why this type of necrosis is often depicted as a combination of both coagulative and
liquefactive necrosis.
- Fat necrosis (in pancreatitis): Fat necrosis is a form of necrosis characterized by the action
upon fat by digestive enzymes. In fat necrosis the enzyme lipase releases fatty acids from
triglycerides. The fatty acids then complex with calcium to form soaps. These soaps appear
as white chalky deposits
- Fibrinoid necrosis (arterial wall): Fibrinoid necrosis is a specific pattern of irreversible,
uncontrolled cell death that occurs when antigen-antibody complexes are deposited in the
walls of blood vessels along with fibrin. It is common in the immune-mediated vasculitis
which are a result of type III hypersensitivity.
Regulated elimination and replacement
Proteins Proteasomal degradation and new synthesis
Parts of cells Autophagy and new synthesis
cells Apoptosis and compensatory cell division
tissues Menstrual cycle, regrowth of liver after partial removal
organism Death and reproduction
When apoptosis?
- Embryonal development: programmed cell death
- Normal tissue homeostasis: cell death and formation of new cells
- Selection of early maturational stages of lymphocytes by antigen receptors
- Involution or atrophy (endometrium during periods; breasts after lactation)
- Termination of inflammatory response or immune reaction
- Elimination of virus-infected cells or cells with other mutations
- Elimination of stressed cells
- Elimination of damaged cells
Pathology 2
, Extrinsic apoptosis-induction
A lethal signal from outside the cell (FasL, TNF) triggers, through receptor activation a cascade that
lead to apoptosis.
Mitochondrial (intrinsic) pathway of apoptosis-induction
Lack of survival signals, or damage, or stress of the cell itself induces apoptosis.
BCL-1 and B-cell (follicular) lymphoma
- Loss of apoptosis response by overexpression of BCL2-gen
- Cause: t(14;18)(q32;q21): BCL2-gen is, by translocation, brought under control of the
promotor of the heavy chain of the immunoglobulin
- Follicular lymphoma is a type of non-Hodgkin lymphoma (NHL). NHL is a cancer of the
lymphatic system. Follicular lymphoma develops when the body makes abnormal B
lymphocytes. These lymphocytes are a type of white blood cell that normally helps us fight
infections. When you have a lymphoma, the abnormal lymphocytes build up in the lymph
nodes or other body organs.
Cytochrome c
- Protein with a heme group, which is present in many unicellular organisms, plants, and
animals.
- Two functions include:
o Electron transport in oxidative phosphorylation
o Induction of apoptosis
Pathology 3
Pathology is the study of the causes and effects of disease or injury. The word pathology also refers
to the study of disease in general, incorporating a wide range of biology research fields and medical
practices. However, when used in the context of modern medical treatment, the term is often
referred to the diagnosis of diseases, mostly through analysis of organs, tissues, cells, and body
fluids.
A disease is any abnormality that causes loss of health and is characterized by a specific set of
features (signs, symptoms, functional and morphological manifestations). Usually, disfunction of an
organ or tissue occurs due to damage to the cells. The damage can be of many causes, chemical,
thermal, radiation, DNA damage, micro bacterial, etc. The damaging agent is the etiology (e.g.,
radiation), the influence on and the changes in cellular processes reflect the pathogenesis.
Multicellular individuals
The social amoeba Dictyostelium discoideum survives periods of food shortage by organizing itself in
a multicellular aggregate → multicellular by choice.
Multicellular individuals: are a niche in nature, with its own possibilities, but also its own problems:
- internal milieu is optimized, and thus also attractive for intruders. Effective defense is
required → Infectious diseases
- organization and clear division of tasks is mandatory, incl. discipline of cells, 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 (adaption)
- damage can be reversible, lead to adaption or, ultimately to cell death.
Cell- & tissue adaption
- hypertrophy: increase in the size of the cells, not an
increase of number
- hyperplasia: increase in the number of cells, not in
the size
- Atrophy: decrease of tissue by decrease of cell size
and/or number
- Metaplasia: replacement of one tissue by a (normal)
other tissue. The most common type of metaplasia is
metaplasia of glandular epithelium into stratified
squamous epithelium. Metaplasia occurs due to
reprogramming of tissue stem cells.
Pathology 1
,Cell death
Necrosis versus apoptosis: the essential difference
Necrosis Apoptosis
Pro-inflammatory Anti-inflammatory
Induces repair and defense No induction of repair or specific defense
Cell contents are released extracellularly Cell contents are not released in surroundings
‘Cellular catastrophe’, no regulation ‘Cellular suicide’, under strict regulation
pathologic Part of normal physiology
Occurs now and then Occurs continuously
→ protein degradation in living cells is due to proteasomal degradation or autophagy.
Types of necrosis:
- Coagulation necrosis: Coagulative necrosis is a type of accidental cell death typically caused
by ischemia or infarction. In coagulative necrosis, the architectures of dead tissue are
preserved for at least a couple of days.
- Colliquative necrosis: Liquefactive necrosis (or colliquative necrosis) is a type of necrosis
which results in a transformation of the tissue into a liquid viscous mass. Often it is
associated with focal bacterial or fungal infections and can also manifest as one of the
symptoms of an internal chemical burn.
- Caseous necrosis (TBC): When the hilar lymph node for instance is infected with tuberculosis
and leads to caseous necrosis, its gross appearance can be a cheesy tan to white, which is
why this type of necrosis is often depicted as a combination of both coagulative and
liquefactive necrosis.
- Fat necrosis (in pancreatitis): Fat necrosis is a form of necrosis characterized by the action
upon fat by digestive enzymes. In fat necrosis the enzyme lipase releases fatty acids from
triglycerides. The fatty acids then complex with calcium to form soaps. These soaps appear
as white chalky deposits
- Fibrinoid necrosis (arterial wall): Fibrinoid necrosis is a specific pattern of irreversible,
uncontrolled cell death that occurs when antigen-antibody complexes are deposited in the
walls of blood vessels along with fibrin. It is common in the immune-mediated vasculitis
which are a result of type III hypersensitivity.
Regulated elimination and replacement
Proteins Proteasomal degradation and new synthesis
Parts of cells Autophagy and new synthesis
cells Apoptosis and compensatory cell division
tissues Menstrual cycle, regrowth of liver after partial removal
organism Death and reproduction
When apoptosis?
- Embryonal development: programmed cell death
- Normal tissue homeostasis: cell death and formation of new cells
- Selection of early maturational stages of lymphocytes by antigen receptors
- Involution or atrophy (endometrium during periods; breasts after lactation)
- Termination of inflammatory response or immune reaction
- Elimination of virus-infected cells or cells with other mutations
- Elimination of stressed cells
- Elimination of damaged cells
Pathology 2
, Extrinsic apoptosis-induction
A lethal signal from outside the cell (FasL, TNF) triggers, through receptor activation a cascade that
lead to apoptosis.
Mitochondrial (intrinsic) pathway of apoptosis-induction
Lack of survival signals, or damage, or stress of the cell itself induces apoptosis.
BCL-1 and B-cell (follicular) lymphoma
- Loss of apoptosis response by overexpression of BCL2-gen
- Cause: t(14;18)(q32;q21): BCL2-gen is, by translocation, brought under control of the
promotor of the heavy chain of the immunoglobulin
- Follicular lymphoma is a type of non-Hodgkin lymphoma (NHL). NHL is a cancer of the
lymphatic system. Follicular lymphoma develops when the body makes abnormal B
lymphocytes. These lymphocytes are a type of white blood cell that normally helps us fight
infections. When you have a lymphoma, the abnormal lymphocytes build up in the lymph
nodes or other body organs.
Cytochrome c
- Protein with a heme group, which is present in many unicellular organisms, plants, and
animals.
- Two functions include:
o Electron transport in oxidative phosphorylation
o Induction of apoptosis
Pathology 3
