Lecture 8 - necrosis

Question 1

Question 2

term necrosis

Answer 2

from Greek nekros, for “corpse”, “death” or “causing to die”
has been used in the last 2000 years, describing the drastic changes in tissue morphology that is visible to the naked eye

Question 3

historically, cell death was thought to be

Answer 3

an abnormal response, all forms were collectively described as necrotic

Question 4

necrosis has originally been considered as an

Answer 4

accidental cell death that operates rather uncontrolled and passively, as a consequence of physical or chemical stress –> as uncontrolled, chaotic, and disordered process of cell destruction

Question 5

necrosis is characterized by

Answer 5

a loss in membrane integrity with subsequent rupture as well as cytoplasmic and organellar swelling

Question 6

cellular swelling prior to necrosis onset has been termed

Answer 6

oncosis derived from “oncos”, meaning swelling

Question 7

Question 8

Question 9

Recommended definition

Answer 9

“Necrosis’ is usually considered as a type of cell death with no signs of apoptosis or of autophagy, which is a negative definition. The morphological appearance of necrosis is often that of oncosis. The expression ‘oncosis’ defines a cell death morphology with cytoplasmic swelling, mechanical rupture of the plasma membrane, dilation of cytoplasmic organelles (mitochondria, endoplasmic reticulum and Golgi apparatus), as well as moderate chromatin condensation. The NCCD recommends limiting the use of the expression ‘oncosis’, as it overlaps with necrosis. Although the name ‘oncosis’ corresponds well to the morphological appearance of this type of cell death, ‘necrosis’ should be maintained for historical reasons.”

Question 10

has been suggested that the signaling for necrosis takes place

Answer 10

long before the manifestation in a morphologically visible necrotic cell death subroutine

Question 11

term necrosis does not precisely indicate the actual

Answer 11

cause of cell death but rather the consequence thereof, manifesting in the above morphology

Question 12

A need to address the scenario where the cell attempts to respond, with a potential apoptotic outcome, however, the circumstances (eg lactic acid accumulation, ion pump failure, increase in osmolarity) are causing the cell to lyse

Question 13

if cellular energetic balance can be maintained sufficiently, to allow ion pump function etc to prevail, necrotic cell death can be avoided, given that the initial insult was temporary in nature and its magnitude below a defined level

Question 14

Question 15

Loss of ATP

Answer 15

(metabolic failure, due to various reasons) is central to necrosis

Question 16

Question 17

Question 18

Question 19

Question 20

Question 21

Question 22

Question 23

Question 24

Loss of membrane integrity, ATP and ATP synthesis are hallmarks for necrosis

Answer 24

Release of LDH
Release of HMGB1
Loss of ATP (to <50%)
Loss of function of ATP generating systems
Loss of lysosomal stability and cathepsin release
Organellar swelling
ROS accumulation

Question 25

Question 26

Question 27

Question 28

What exactly is happening inracellularly?

Answer 28

Membranes start to become leaky:

threshold of metabolic collapse,
ion balance collapse
lysosomal enzyme release (ATP-ases)

The progression in these events determine reversibility, governed by the severity of initial insult and duration of the initial insult

Question 29

Question 30

Question 31

Question 32

Necrosis-physiological role

Answer 32

plays an important role in the maintenance of physiologic conditions

Inducing an inflammatory response, provokes strong inflammatory responses and cytokine production

maintain tissue and organism integrity by initiating adaptive and reparative responses in the host (release of TNF-α, cytokines, heat shock proteins (HSP), HMGB1)

Question 33

Question 34

Question 35