MCB Lecture 57 Cell Death Flashcards
Describe necrosis
This is the morphological features of cells after it has died due to a pathological injury
The cell did not control the death
What are the two modes of cell death?
Apoptosis and Necrosis
What is apoptosis?
Apoptosis is the highly controlled and regulated death of a cell
What causes cell death by necrosis?
What causes cell death by apoptosis?
Necrosis: pathological stress
Apoptosis: physiological or pathological
Describe the morphology of necrotic cells
Increased eosinophilia staining Nucleus: pyknosis, karyolysis, karyorrhexia Myelin figures Membranes are burst Organelles have been digested
What are myelin figures, and when are they produced?
Myelin figures are whorls of phospholipid from the cell membrane that has been disrupted
They are produced in irreversible cell damage
Describe the different morphologies of the nucleus that are seen in necrosis
Karyolysis: nucleic acid has been degraded (decreased basophilia)
Pyknosis: condensation of the nucleic acid (increased basophilia)
Karyorrhexia: fragmentation of the nucleic acid
What does the appearance of necrotic tissue depend on?
Depends on which type of necrosis has occured, ie. coagulation or digestion of the protein in the tissues
Balance between coagulation and liquefactive
What are the six types of necrosis?
Coagulative Liquefactive Caseous Fat necrosis Fibrinoid Gangrenous
What causes coagulative necrosis?
Severe ischemia
What causes liquefactive necrosis?
Bacterial or fungal infection
What causes caseous necrosis?
Mycobacterium tuberculosis infection
What causes fat necrosis?
Acute pancreatitis
What causes fibrinoid necrosis?
Immune vasculitis
What causes gangrenous necrosis?
Blood supply to a lower extremity is cut off
Bacterial infection (wet necrosis)
Describe the features of coagulation necrosis
Denaturant ion of the enzymes within cells
Cell architecture is maintain
Cells are dead, nucleus is gone
Describe the features of liquefactive necrosis
Digestion of the proteins of cells
Cell architecture is gone
Fluid filled cysts form
Ischemia in the brain leads to which type of necrosis?
What is the morphology?
Liquefactive, a fluid filled cyst forms
Where does coagulative necrosis mostly occur?
Solid organs
What are the features of caseous necrosis?
This is when both liquefactive and coagulative are occurring
The tissue has a crumbly texture like cheese
The tissue architecture is lost
What is happening in fibrinoid necrosis?
Proteinaceious material is deposited in the tissue matrix and fibrin plugs in the blood vessels
Deposition of immune complexes in the blood vessels
Where does fibrinoid necrosis occur?
In the tissue matrix and in the lumen of blood vessels
Where does gangrenous necrosis occur?
Extremities, eg. Feet
What is wet gangrene
This is when there is liquefactive necrosis occurring as well, in response to a bacterial infection
What is going on in gangrene?
Blood supply to the extremity is lost, and the cells undergo coagulative necrosis (and sometimes liquefactive)
Describe the morphology of cells undergoing apoptosis
Cell shrinks in size Nucleus condenses and fragments Apoptotic bodies form Organelles are digested Cytoplasmic is intensely eosinophilic
Which physiological stimuli cause apoptosis?
a. Embryogenesis: eg. Developing digits
b. Involution: shrinking of an organ, eg. Uterus after pregnancy
c. Removing cells at their use by date
d. Autoreactive T lymphocytes
e. CD8+ killing
Which pathological stimuli cause apoptosis?
a. Growth factor deprivation
b. DNA damage
c. Accumulation of misfolded protein
d. Infection
e. Atrophy
What are the two apoptotic pathways?
Intrinsic: Mitochondrial
Extrinsic: Death receptor
What are the stimuli for the intrinsic pathway?
a. DNA damage
b. Misfolded protein
c. GF withdrawal
Describe the intrinsic apoptotic pathway
- Stimulus detected by Bcl-2 family receptor
- Activation of Bcl family effectors (Bax, Bak)
- Signalling to mitochondria to
4a. Release cytochrome c
4b. Release pro-apoptotic proteins - Initiator caspases
Regulation:
Bcl-2 and Bcl-x
Which stimuli activate the extrinsic pathway?
Cytotixic T cell killing (Fas, Fas-l)
Removal of autoreactive lymphocytes
Describe the death receptor pathway
1. Ligand - receptor interaction Fas & Fas-L TNF & TNF-Receptor 2. Adaptor proteins 3. Initiator caspases
Where do the two apoptotic pathways converge?
At the initiator caspases
Can the two cell death pathways coexist?
Yes they often do
What is inflammation?
Response to eliminate the cause and consequence of injury
What happens if we don’t have inflammation?
A wound or injury will never heal
Which suffix denotes inflammation
-itis
What is fat saponification, and when does it occur?
Fat saponification is the break down of the membranes of fat cells, releasing fatty acids
The fatty acids combine with extracellular calcium to form the patchy white lesions
What is Bcl-2, Bax, Bak and Bcl-x?
Bcl-2: B-cell lymphoma receptor, receptor in the intrinsic pathway of apoptosis
Bax: Bcl-2 associated X protein
Bak: Bcl-2 homologous antagonist killer
These are effector proteins of apoptosis
Bcl-x negative inhibitor
Describe the apoptotic pathway after the convergence of the signals
- Initiator caspases
- Executioner caspases
- Degredation of protein (nuclear, cytosolic, membrane, cytoskeleton)
- Formation of apoptotic bodies
- Phagocytosis of the apoptotic bodies
What stimulation do phagocytes get to come and eat the apoptotic bodies?
- Dying cells release factors that attract phagocytes
2. Phosphatidyl serine flip detected
Compare the organelles in reversible and necrosis
Reversible: swollen
Necrosis: digested
Compare the cell membrane in reversible and necrosis
Reversible: blebs
Necrosis: discontinuous
Compare the mitochondria in reversible and irreversible
Reversible: swollen
Irreversible: lost the membrane potential & cytochrome c
Which is the most common type of necrosis?
Coagulative
DNA damage is one of the stimuli for the intrinsic pathway of apoptosis.
Describe how this may occur
- Radiation
- UV damage
- Infection
- Hypoxia
- ROS
Why is cell death triggered when there is DNA damage?
To prevent propagation of the mutated DNA
Misfolded proteins are one of the triggers of the intrinsic apoptosis pathway.
How does this arise?
- Mutation
- Extrinsic factors
Compare cell size in apoptosis and necrosis
Apoptosis: shrunken
Necrosis: swollen
