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Think not disdainfully of death, but look on it with favor; for even death is one of the things that Nature wills. - PowerPoint Presentation
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Think not disdainfully of death, but look on it with favor; for even death is one of the things that Nature wills. - - PowerPoint PPT Presentation


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Golden lads and girls all must, As chimney-sweepers, come to dust. - William Shakespeare, Cymbeline (Guiderius at IV, ii). Think not disdainfully of death, but look on it with favor; for even death is one of the things that Nature wills. - Marcus Aurelius Antoninus

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slide1

Golden lads and girls all must,

As chimney-sweepers, come to dust.

- William Shakespeare, Cymbeline (Guiderius at IV, ii)

Think not disdainfully of death, but look on it with favor; for even death is one of the things that Nature wills.

- Marcus Aurelius Antoninus

(121-180) Emperor of Rome 161–180, distinguished Stoic philosopher

Meditations

death disaster or design

Death: Disaster or Design?

Necrosis versus Apoptosis

Dr Geoffrey Rowden Pathology Dept.

Dalhousie University

geoffr@dal.ca

outline
Outline
  • Cell damage and death - relationship to disease
  • Disastrous death – Swelling (Oncosis) followed by necrosis (Since 1870 or so)
  • Planned cell death – Apoptosis with or without necrosis (Since 1974 or so)
slide4

Rudolf Virchow – (1821-1902)

“All diseases are traceable to alterations in cells”

cells response to stress
Cells response to Stress
  • Adapt and live on at a lower or higher state of activity
  • Fail to cope with the stress and die
traditional cell death
Traditional cell death
  • Cells swell because they lose the ability to maintain salt balances across their membranes –”pump failure”
  • Mostly due to shutdown of energy generation by Mitochondria
  • Termed Necrosis – but should be called Oncosis
post oncosis coagulative necrosis
Post-Oncosis Coagulative Necrosis
  • Commonest form
  • Main causes - Ischemia (no blood flow)/hypoxia (no oxygenation)
  • Protein denaturation with little initial enzyme activation - Lack of water
  • Cell outlines initially preserved
  • Eosinophilic (Pink stained) cytoplasm
  • EXAMPLE: Myocardial infarct
oncosis accidental cell death
Oncosis (Accidental Cell Death)
  • “Accidental death” is typified by cell swelling due to energy depletion and ion pump failure. Necrosis is the post mortem result.
  • Release of cell contents provokes an inflammatory response. Not seen in apoptosis.
apoptosis
Apoptosis
  • First described in 1974 – John Kerr
  • Programmed cell death
  • Other names: Necrobiosis, Shrinkage necrosis, Single cell deletion.
  • Counterbalance to mitosis.
oncosis versus apoptosis
Oncosis Versus Apoptosis
  • Apoptosis is the defaultdisposal system to delete cells that have accumulated unrepairable DNA damage. Genomic integrity is protected . May have arisen in response to viral attack on cells.
  • Stereotyped morphologic pattern.
  • Linkage to DNA repair systems like p53 (Guardian of the genome).
role in tissue homeostasis
Role in Tissue Homeostasis
  • Predictable developmental remodeling. e.g. tadpole tail, digits, soft palate kidney remodelling, brain development, etc.
  • Adult remodeling e.g.cyclical proliferation/atrophy as in the endometrium, breast or hair follicles.
  • Gene regulated.
apoptosis neural development
Apoptosis - Neural Development

Surplus neurons deleted

dna ladders
DNA Ladders

DNA is chopped up in a controlled manner

genes of cell death
Genes of Cell Death
  • Caenorhabditis elegans (a nematode) deletes 131 cells by apoptosis during the development from egg to adult.
  • Mutations identify genes (ced 3/4 ) as necessary for cell death. (pro-apoptotic).
  • Ced 9 gene is anti-apoptotic and Bcl-2 is the mammalian homologue.
poison cupboard of caspases
Poison Cupboard of Caspases
  • The enzymes that do the controlled chopping
  • Cysteine proteases with preference for cleavage at an aspartate residue.
  • Activation of pro-caspases e.g. caspase 8
  • Cascade of caspase activation. e.g. c10, c3, c7, c6, c2.
slide26

Must not all things at the last be swallowed up in death?

Plato (427 BC - 347 BC), Dialogues, Phaed

bcl 2 family
Bcl-2 Family
  • Anti-apoptotic - Bcl-2 , - mostly membrane associated, especially on mitochondrial outer membranes.
  • Pro-apoptotic - Bax, - cytoplasmic. Form competitive links to dimerize with Bcl-2. Inactivate the protective functions.
bcl 2 bax and cancer
Bcl-2/Bax and Cancer

How the balance shifts to cause more or less cells surviving

recap
Recap
  • Cell damage and death - relationship to disease
  • Disastrous death – Swelling (Oncosis) followed by necrosis
  • Planned cell death – Apoptosis with or without necrosis
slide33

For three days after death hair and fingernails continue to grow but phone calls taper off.

Johnny Carson