Cell Injury And Death Notes

Question 1

What factors determine the degree of cell injury

Answer 1

Type of injury
Severity of injury
Duration of injury
Type of tissue

Question 2

List the causes of cell injury

Answer 2

Environmental:
Hypoxia
Toxins/poisons
Immune mediated
Physical agents
Infections
Nutritional/dietary

Non-environmental:
Genetic
Ageing

Question 3

Describe the different causes of hypoxia

Answer 3

1. Hypoxaemic hypoxia - arterial content of oxygen is low
2. Anaemia hypoxia - decreased ability of haemoglobin carry oxygen
3. Ischaemic hypoxia - interruption to blood supply
4. Histiotoxic hypoxia - inability to utilise oxygen due to disabled oxidative phosphorylation enzymes

Question 4

What are the 2 mechanisms of immune mediated cell injury?

Answer 4

Hypersensitivity reactions - secondary to excessive immune reaction to non-self antigens

Autoimmune reactions - immune system over reacts to a self antigen causing tissue damage

Question 5

What are the physical agents that lead to cell injury and death?

Answer 5

Trauma
Extreme temperature
Electric currents
Radiotherapy

Question 6

What can cause infection leading to cell damage?

Answer 6

Bacteria
Virus
Parasite
Fungi

Question 7

What are the nutritional/dietary causes of cell damage?

Answer 7

Obesity
Anorexia
Dietary deficiencies or excess

Question 8

What are the genetic/age causes of cell damage?

Answer 8

Inborn errors in metabolism
Enzyme deficiencies
Dysfunctional proteins

Question 9

What are the 6 mechanisms of cell injury

Answer 9

Depletion of ATP
Direct mitochondrial damage
Direct membrane damage
Disruption to calcium homeostasis
Oxidative stress
Direct damage to DNA and proteins

Question 10

How can calcium influx cause irreversible damage?

Answer 10

Can activate ATPases, phospholipases, proteases and endonucleases

Question 11

What can free radicals damage within cells?

Answer 11

Lipids, proteins and DNA

Question 12

Describe free radical damage of lipids

Answer 12

Unsaturated fatty acids get attacked by free radicals. This causes cell membrane and organelle damage, resulting in calcium influx, damage to Na/K pump etc.

Question 13

Describe free radical damage of protein

Answer 13

Promotes protein-protein cross links (disulphide bonds) and oxidation of proteins.
This causes protein fragmentation and thus cell damage

Question 14

Describe free radical damage of DNA

Answer 14

Free radicals target nuclear and mitochondrial DNA
They cause single and double strand breaks in DNA

Question 15

how does the body remove free radicals?

Answer 15

Anti-oxidants
Transport proteins
Enzymes

Question 16

How does the body control free radical damage?

Answer 16

Heat shock proteins e.g. ubiquitin.
They help repair and re-fold damaged proteins, or they label them for degradation
In times of stress, all cells reduce their usual protein synthesis and increase heat shock protein synthesis

Question 17

Describe reversible and irreversible cell injury

Answer 17

Reversible:
Swelling
Clumped chromatin
Ribosome dispersion
Cystoplasmic ‘blebs’ (membrane is intact)

Irreversible:
Nuclear changes
Membrane defects
Lysosome rupture
Lysis of endoplasmic reticulum

Question 18

What are the differences between physiological and pathological apoptosis?

Answer 18

Physiological - embryogenesis

Pathological - cell death in viral infection

NOTE: in apoptosis, cells shrink, no inflammation, neat and tidy

Question 19

What are the 2 pathways of apoptosis?

Answer 19

Intrinsic (mitochondrial) - mitochondria release cytochrome C which activates caspases which induce apoptosis

Extrinsic (death receptor) - death receptors (secreted from T killer cells) attach to the cell membrane which then activate caspases which lead to cell death

Question 20

Describe necrosis

Answer 20

Cells swell, disorganised and messy

Characteristic nuclear changes: pyknosis (shrinkage), karyorrhexis (fragmentation), karyolysis (dissolution)

Types of necrosis: coagulative, liquefactive, caseous, fat necrosis, fibrinoid necrosis

Question 21

Describe coagulative necrosis

Answer 21

Solid organs
Retains ghost outline of cells and tissue architecture
Protein desaturation prominent in the cell injury/death

Question 22

Describe liquefactive necrosis

Answer 22

Damage of ‘loose’ tissue
Complete loss of architecture
Release of enzymes which break down tissue

Question 23

Describe fat necrosis

Answer 23

Due to direct trauma to fatty areas and acute pancreatitis

Question 24

What molecules are released by injured cells?

Answer 24

Potassium
Enzymes
Myoglobin

Question 25

Cell injury causes deranged metabolism. What can accumulate within cells due to this?

Answer 25

Normal cell components - e.g. cerebral oedema: hypoxic cell injury -> sodium enters cell, water follows -> cell swelling Abnormal cell components - e.g. fatty liver disease: liver cell injury -> deranged metabolism -> fat accumulation within hepatocytes Pigment - e.g. tattoo: artificial pigment into skin -> pigment phagocytosed by macrophages -> pigment remains in macrophages of dermis

Question 26

What is gangrene?

Answer 26

Necrosis visible to the naked eye

Question 27

what is an infarction?

Answer 27

Necrosis caused by reduction in arterial blood flow - a cause of necrosis Can result in gangrene

Question 28

What is ischaemia?

Answer 28

Inadequate blood supply to tissue Can result in infarction

Question 29

Hat is the difference between dry and wet gangrene?

Answer 29

Both involve necrosis Dry - exposure to air. Coagulative necrosis Wet - infection. Liquefactive necrosis

Question 30

What is the difference between white and red infarct?

Answer 30

White: No associated haemorrhage. Occlusion of an end artery -> often wedge shaped Red: Haemorrhage (into dead tissue) Organs with a dual blood supply Previous vascular congestion

Question 31

What is pathological calcification? What are the two different types?

Answer 31

Abnormal deposition of calcium within tissues 1) Localised in dying tissue (dystrophic) - most common; nothing to do with calcium metabolism 2) Generalised (metastatic) - deposition in otherwise normal tissue; metabolic error causing high levels of circulating calcium; can be fatal