Intro - some of apoptosis and necrosis

Question 1

Is apoptosis energy dependent?

Answer 1

yes

Question 2

List some inhibitors of apoptosis

Answer 2

growth factors
extracellular matrix
sex steroids
some viral proteins

Question 3

List some inducers of apoptosis

Answer 3

Lack of growth factors
loss of matrix attachment
glucocorticoids
some viruses
free radicals
ionising radiation
DNA damage

Question 4

Which family has both pro and anti-apoptotic members

Answer 4

BcI-2 (includes BcI-2 and Bax)
They are the intrinsic apoptosis pathway
The ratio of BcI-2 to Bax determines cell’s susceptibility to apoptosis stimuli

Question 5

What does BcI2 do

Answer 5

Inhibits caspases and therefore apoptosis

when an inhibitor triggers it

Question 6

What does Bax do

Answer 6

Promotes caspases to apoptose the cell

when p53 or an inducer stimulates it

Question 7

What does the Fas receptor do

Answer 7

It is a death receptor.
When a Fas ligand bind to it, it causes a cascade of event culminating in caspases becoming active and apoptosing the cell.
It is on the surface so is part of the extrinsic apoptosis pathway.
Note this is the mechanism the immune system uses to eliminate self-antigen producing lymphocytes

Question 8

What does the p53 gene do?

Answer 8

Codes p53 which is a protein that is produced when there is DNA damage (so technically is a sense of whether DNA damage is present or not)

Question 9

What does the p53 protein do?

Answer 9

It can take the cell out of the cell cycle and induce either DNA damage repair (and then cell division) or apoptosis via activation of Bax

Question 10

What is Coagulative necrosis?

Answer 10

Commonest
Thick and gooey - caused by ISCHAEMIA -> cells retain their outline as proteins coagulate and metabolic activity stops (firm) -> the inflammatory response is triggered -> digestion by macrophages -> soft texture

Question 11

What is a risk of coagulative necrosis?

Answer 11

Organ rupture e.g. if this occurs after an MI then the ventricle can rupture

Question 12

What is liquefactive/colliquative necrosis?

Answer 12

Necrotic area liquifies e.g. brain, due to lack of stromal support

Question 13

What is caseous necrosis?

Answer 13

Looks like soft cheese
TB is characterised by this
multinucleate giant cells present

Question 14

What is gangrenous necrosis?

Answer 14

Affected tissue is black due to iron deposits from degraded Hb
ISCHAEMIA may lead to this type of necrosis or certain BACTERIA e.g. clostridia

Question 15

What is fibrinoid necrosis?

Answer 15

Arterioles under so much PRESSURE that there is necrosis of smooth muscle wall and plasma leaks out and deposits fibrin in the media

Question 16

What is fat necrosis?

Answer 16

TRAUMA e.g. to the breast, to the adipose tissue and fat moves extracellularly.
Then there’s a brisk inflammatory response ultimately leading to phagocytosis of the fat and fibrosis (so palpable mass)

Question 17

General causes of necrosis

Answer 17

O2 lack (anaerobic -> acidotic -> Ca inflow -> mitochondrial Ca overload -> mitochondrial membranes fail -> no ATP -> mitochondrial contents leaks into cytoplasm -> ROS burst -> DNA damage)
Mitochondrial failure (no ATP -> ion pumps stop -> no homeostasis -> water influx -> lysis -> cell death)
Trauma
High pressure in vessels
Damage to ion pumps (see first point)
Free radicals, radiation, poisons (damage membranes and pathways)