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Cell death
Cellular adaption
• Atrophy- decrease in cell size
• Hypertrophy- increase in cell size
• Hyperplasia- increase in number of cells
• Metaplasia- one cell form to another
• Dysplasia- change is cellular shape
https://www.slideshare.net/DeepakKuma
rGupta2/cellular-adaptation-53513522
Example of apoptosis in embryo
https://www.khanacademy.org/science/biology/developmental-biology/apoptosis-in-development/a/apoptosis
Human embryo hand
development inutero
Apoptosis versus necrosis
https://www.gregtrimble.com/to-the-litterbug-that-threw-a-starbucks-cup-out-their-car-window/
Apoptosis
Necrosis
https://www.123rf.com/photo_87383404_stock-vector-trash-in-garbage-cans-with-sorted-garbage-vector-icons-recycling-garbage-separation-collection-and-r.html
Apoptosis programmed cell death
• Apoptosis means- dropping off
• Reference to dropping off cell that are no
longer useful
• Part of normal development
– Apoptosis prunes the embryonic ducts during
gender specific development
• Tissue turnover
• Role in the immune system
• Undesirable cells
Role of apoptosis
Key roles in-
• Growth
• Immune surveillance
• Neoplastic development
https://slideplayer.com/slide/4446840/
Cycle of apoptosis
Extrinsic apoptosis
Intrinsic apoptosis
• Bcl-2 controlled pathway
• Activation of caspases from inside the cell
• Formation of an intracellular caspase-9-activating
complex (apoptosome)
• Apoptosome forms after cytochrome c is released
from the mitochondria
Apoptosome
Bcl-2 family
• Consists of a hydrophobic α-helix surrounded by amphipathic
α-helices
• Some members of the family have transmembrane domains at
their c-terminus
• Bcl2 stops channel formation on the surface of mitochondria so
cytochrome c not released through the channel
https://www.easybiologyclass.com/intrinsic-pathway-of-apoptosis-apoptosis-molecular-mechanism-part-1/
Caspase
• Cysteine protease
• The intrinsic apoptotic pathway is characterized by
permeabilisation of the mitochondria and release
of cytochrome c into the cytoplasm.
• Cytochrome c then forms a multi-protein complex
known as the "apoptosome" and initiates activation of
the caspase cascade through caspase 9
https://www.slideshare.net/dineshthangavel1/apoptosis-9298529
Overview of the apoptotic pathway
https://oncohemakey.com/the-scientific-basis-of-cancer/
Morphological features of apoptosis in
comparison
• Chromatin aggregation - nuclear and cytoplasmic
condensation to form apoptotic bodies
• Organelles remain intact
• Intact membrane surrounds apoptotic bodies
• No inflammatory response
• Apoptotic bodies phagocytosed by adjacent cells and
macrophages
• Typically affects isolated cells
• Surrounding cells remain in tact
https://www.youtube.com/watch?v=-
vmtK-bAC5E
Neurodegeneration from apoptosis
• Huntingdon's disease
• Alzheimer's
• Parkinson’s
https://www.dreamstime.com/stock-illustration-apoptosis-neuron-which-observed-different-diseases-such-as-viral-encephalitits-neurodegenerative-psychiatric-image79864414
Apoptotic nerve cells
Genetic defects in apoptosis
• Mutations rare but-
• Common mutation in Fas gene
• Mutation in FasL gene
• Caspase-1 mutation occurs rarely (NALP3
gene)
Autoimmune lymphoproliferative disorder
(ALPD)
Necrosis un-programmed cell
death
Necrosis means making dead
Accidental death of cells through-
• Injury
• Infection
• Cancer
• Infarction
• Toxins
• Inflammation
• No regulated signals to phagocytes to ‘clear’
necrotic cells and avoid immune surveillance
https://www.youtube.com/watch?v=vAYB6QWuOdM
Chromatin aggregation
Mechanism of necrosis
• Unable to pump out Na+
• Cell swells though osmosis
• Insult of necrosis injures many surrounding
cells
• Intracellular products initiate an inflammatory
response
• This can harm surrounding healthy tissues
Detailed events of necrosis
• Cell shrinkage and rounding occur because of the
retraction lamellipodia and the breakdown of the proteinaceous
cytoskeleton by caspases.
• Mitochondria become ‘leaky’
• The cytoplasm appears dense, and the organelles appear tightly
packed.
• Chromatin undergoes condensation into compact patches against
the nuclear envelope (also known as the perinuclear envelope) in a
process known as pyknosis, a hallmark of apoptosis.
• The nuclear envelope becomes discontinuous and the DNA inside it
is fragmented in a process referred to as karyorrhexis. The nucleus
breaks into several discrete chromatin bodies ornucleosomal
units due to the degradation of DNA
Cell shrinkage and rounding occur because of the
retraction lamellipodia and the breakdown of the proteinaceous
cytoskeleton by caspases.
Leaky mitochondria
Intrinsic apoptosis
Morphological features of Necrosis
Cell membrane integrity lost and lysosomal hydrolases
released, resulting in -
• Nuclei small, condensed
• Pyknosis- nuclei stain deeply with hematoxylin (basophilic)
• Karyorrhexis- nuclei fragmented into particles
• Karyolysis- nuclear lysis
• Cytoplasm deeply eosinophilic (RNA loss, protein
coagulation)
• Typically affects large groups of cells
https://en.wikipedia.org/wiki/Pyknosis
Morphological patterns of Necrosis
• Coagulative necrosis, typically in hypoxic cells with few
lysosomes
• MI
• Infarct of spleen
• Liquifactive necrosis in cells with numerous lysosomes
or where bacteria attract neutrophils
• Pneumonia
• Brain hypoxia
• Gummatous necrosis restricted to spirochaetal infections
• Syphylis
• Haemorrhagic necrosis - blockage of venous drainage
of tissue or organ
• eg. Testicular torsion
Types of necrosis
Coagulative necrosis Liquefactive necrosis
Digestive release of lysosomal enzymes
turn tissue into pus (CNS)
Can also occur in lungs with abscesses
Typically occurs with infarcts or ischemia
Architecture of dead tissue preserved
`regeneration can occur with enough viable cells
Types of necrosis
Fat necrosis Fibrinoid necrosis
Seen in autoimmune diseases, vasculitisChalky white deposites
Examples of different types of necrosis
Caseous necrosis
Cheese like, yellow-white area
Combines features of Coagulative and liquefative.
Found in centre of tuberculous infections
Gumatous necrosis
Rubbery texture of tissue of the hard pallet
Diseases associated with necrosis
• Autoimmune vasculitis
• Peripheral vascular disease
• Osteonecrosis of the jaw
• Aseptic bone necrosis
• Gangrene
• Ishaemic cascade (stroke)
• Necrotoxins cause necrosis
• Cystic medial necrosis
• Tumour necrosis due to hypoxia-angiogenesis
Gangrenous necrosis
Irreversible versus reversible necrosis
Irreversible
• Cell digestion by lytic
enzymes
• Protein denaturation
• Hypoxia, chemical and
physical agents, microbial,
immunological injury
Reversible
Initiator caspases
Cell Death
Necrosis
• Pathological cell death - external factors
• Hypoxia, chemical toxins cause necrosis
• Damage to cell physiology
• Degradation of the cell
• Influx of water and ions
• Cellular organelles swell and rupture
Apoptosis
• Programmed or physiological cell death
• Constituent genes cause cell death
ApoptosisNecrosis
Morphological patterns of Necrosis
• Coagulative necrosis, typically in hypoxic cells with few
lysosomes
• MI
• Infarct of spleen
• Liquifactive necrosis in cells with numerous lysosomes
or where bacteria attract neutrophils
• Pneumonia
• Brain hypoxia
• Gummatous necrosis restricted to spirochaetal infections
• Syphylis
• Haemorrhagic necrosis - blockage of venous drainage
of tissue or organ
• eg. Testicular torsion
Diseases associated with necrosis
• Autoimmune vasculitis
• Peripheral vascular disease
• Osteonecrosis of the jaw
• Aseptic bone necrosis
• Gangrene
• Ishaemic cascade (stroke)
• Necrotoxins cause necrosis
• Cystic medial necrosis
• Tumour necrosis due to hypoxia-angiogenesis
Etiological Importance of Apoptosis
• Suppressed apoptosis
– Neoplasia
– Autoimmunity
• Abnormally induced
– AIDS
– Neurodegenerative disease
https://www.khanacademy.org/scienc
e/biology/developmental-
biology/apoptosis-in-
development/a/apoptosis

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Cell death

  • 2. Cellular adaption • Atrophy- decrease in cell size • Hypertrophy- increase in cell size • Hyperplasia- increase in number of cells • Metaplasia- one cell form to another • Dysplasia- change is cellular shape https://www.slideshare.net/DeepakKuma rGupta2/cellular-adaptation-53513522
  • 3.
  • 4. Example of apoptosis in embryo https://www.khanacademy.org/science/biology/developmental-biology/apoptosis-in-development/a/apoptosis
  • 7. Apoptosis programmed cell death • Apoptosis means- dropping off • Reference to dropping off cell that are no longer useful • Part of normal development – Apoptosis prunes the embryonic ducts during gender specific development • Tissue turnover • Role in the immune system • Undesirable cells
  • 8. Role of apoptosis Key roles in- • Growth • Immune surveillance • Neoplastic development https://slideplayer.com/slide/4446840/
  • 10.
  • 12. Intrinsic apoptosis • Bcl-2 controlled pathway • Activation of caspases from inside the cell • Formation of an intracellular caspase-9-activating complex (apoptosome) • Apoptosome forms after cytochrome c is released from the mitochondria
  • 14. Bcl-2 family • Consists of a hydrophobic α-helix surrounded by amphipathic α-helices • Some members of the family have transmembrane domains at their c-terminus • Bcl2 stops channel formation on the surface of mitochondria so cytochrome c not released through the channel
  • 16. Caspase • Cysteine protease • The intrinsic apoptotic pathway is characterized by permeabilisation of the mitochondria and release of cytochrome c into the cytoplasm. • Cytochrome c then forms a multi-protein complex known as the "apoptosome" and initiates activation of the caspase cascade through caspase 9
  • 18. Overview of the apoptotic pathway https://oncohemakey.com/the-scientific-basis-of-cancer/
  • 19. Morphological features of apoptosis in comparison • Chromatin aggregation - nuclear and cytoplasmic condensation to form apoptotic bodies • Organelles remain intact • Intact membrane surrounds apoptotic bodies • No inflammatory response • Apoptotic bodies phagocytosed by adjacent cells and macrophages • Typically affects isolated cells • Surrounding cells remain in tact
  • 20. https://www.youtube.com/watch?v=- vmtK-bAC5E Neurodegeneration from apoptosis • Huntingdon's disease • Alzheimer's • Parkinson’s https://www.dreamstime.com/stock-illustration-apoptosis-neuron-which-observed-different-diseases-such-as-viral-encephalitits-neurodegenerative-psychiatric-image79864414
  • 22. Genetic defects in apoptosis • Mutations rare but- • Common mutation in Fas gene • Mutation in FasL gene • Caspase-1 mutation occurs rarely (NALP3 gene) Autoimmune lymphoproliferative disorder (ALPD)
  • 23. Necrosis un-programmed cell death Necrosis means making dead Accidental death of cells through- • Injury • Infection • Cancer • Infarction • Toxins • Inflammation • No regulated signals to phagocytes to ‘clear’ necrotic cells and avoid immune surveillance https://www.youtube.com/watch?v=vAYB6QWuOdM
  • 25. Mechanism of necrosis • Unable to pump out Na+ • Cell swells though osmosis • Insult of necrosis injures many surrounding cells • Intracellular products initiate an inflammatory response • This can harm surrounding healthy tissues
  • 26. Detailed events of necrosis • Cell shrinkage and rounding occur because of the retraction lamellipodia and the breakdown of the proteinaceous cytoskeleton by caspases. • Mitochondria become ‘leaky’ • The cytoplasm appears dense, and the organelles appear tightly packed. • Chromatin undergoes condensation into compact patches against the nuclear envelope (also known as the perinuclear envelope) in a process known as pyknosis, a hallmark of apoptosis. • The nuclear envelope becomes discontinuous and the DNA inside it is fragmented in a process referred to as karyorrhexis. The nucleus breaks into several discrete chromatin bodies ornucleosomal units due to the degradation of DNA
  • 27. Cell shrinkage and rounding occur because of the retraction lamellipodia and the breakdown of the proteinaceous cytoskeleton by caspases.
  • 29.
  • 31. Morphological features of Necrosis Cell membrane integrity lost and lysosomal hydrolases released, resulting in - • Nuclei small, condensed • Pyknosis- nuclei stain deeply with hematoxylin (basophilic) • Karyorrhexis- nuclei fragmented into particles • Karyolysis- nuclear lysis • Cytoplasm deeply eosinophilic (RNA loss, protein coagulation) • Typically affects large groups of cells
  • 33. Morphological patterns of Necrosis • Coagulative necrosis, typically in hypoxic cells with few lysosomes • MI • Infarct of spleen • Liquifactive necrosis in cells with numerous lysosomes or where bacteria attract neutrophils • Pneumonia • Brain hypoxia • Gummatous necrosis restricted to spirochaetal infections • Syphylis • Haemorrhagic necrosis - blockage of venous drainage of tissue or organ • eg. Testicular torsion
  • 34. Types of necrosis Coagulative necrosis Liquefactive necrosis Digestive release of lysosomal enzymes turn tissue into pus (CNS) Can also occur in lungs with abscesses Typically occurs with infarcts or ischemia Architecture of dead tissue preserved `regeneration can occur with enough viable cells
  • 35. Types of necrosis Fat necrosis Fibrinoid necrosis Seen in autoimmune diseases, vasculitisChalky white deposites
  • 36. Examples of different types of necrosis Caseous necrosis Cheese like, yellow-white area Combines features of Coagulative and liquefative. Found in centre of tuberculous infections Gumatous necrosis Rubbery texture of tissue of the hard pallet
  • 37. Diseases associated with necrosis • Autoimmune vasculitis • Peripheral vascular disease • Osteonecrosis of the jaw • Aseptic bone necrosis • Gangrene • Ishaemic cascade (stroke) • Necrotoxins cause necrosis • Cystic medial necrosis • Tumour necrosis due to hypoxia-angiogenesis Gangrenous necrosis
  • 38. Irreversible versus reversible necrosis Irreversible • Cell digestion by lytic enzymes • Protein denaturation • Hypoxia, chemical and physical agents, microbial, immunological injury Reversible
  • 39.
  • 40.
  • 42.
  • 43. Cell Death Necrosis • Pathological cell death - external factors • Hypoxia, chemical toxins cause necrosis • Damage to cell physiology • Degradation of the cell • Influx of water and ions • Cellular organelles swell and rupture Apoptosis • Programmed or physiological cell death • Constituent genes cause cell death
  • 44.
  • 46. Morphological patterns of Necrosis • Coagulative necrosis, typically in hypoxic cells with few lysosomes • MI • Infarct of spleen • Liquifactive necrosis in cells with numerous lysosomes or where bacteria attract neutrophils • Pneumonia • Brain hypoxia • Gummatous necrosis restricted to spirochaetal infections • Syphylis • Haemorrhagic necrosis - blockage of venous drainage of tissue or organ • eg. Testicular torsion
  • 47. Diseases associated with necrosis • Autoimmune vasculitis • Peripheral vascular disease • Osteonecrosis of the jaw • Aseptic bone necrosis • Gangrene • Ishaemic cascade (stroke) • Necrotoxins cause necrosis • Cystic medial necrosis • Tumour necrosis due to hypoxia-angiogenesis
  • 48. Etiological Importance of Apoptosis • Suppressed apoptosis – Neoplasia – Autoimmunity • Abnormally induced – AIDS – Neurodegenerative disease