Cell Injury And Cell Death

Question 0

What are the causes of cell injury?

Answer 0

Hypoxic states
Ischemia: obstruction of blood flow
Anaemia: reduction in the number of RBC meaning less transport of O2.

Other causes
Physical agents: trauma, extremes of heat and cold, radiation.
Chemical agents: drugs, toxins
Infectious agents: bacteria, viruses, parasites, fungus
Free radicals
Genetic derangement: mutations, chromosomal abnormalities.

Question 1

What will happen to the liver if excessive alcohol is used over a long period?

Answer 1

Fatty change in the liver whereby the cytoplasm has a foamy or bubbly appearance which can be recovered to normal.

Question 2

Give three examples of how different cells show responses to injury.

Answer 2

Parenchymal cells are more sensitive than stromal cells
Brain and heart muscle cells are more susceptible to hypoxia and Ischemia, neuron dies in 3-4 minutes
Calf muscle tolerate 2-3 hours of Ischemia whereas cardiac muscle dies within 30 minutes.

Question 3

What are the mechanisms of cellular injury and what are the etiological agents?

Answer 3

Deficiency of metabolites including oxygen, glucose, hormones

Mechanical disruption caused by trauma and osmotic pressure

DNA damage or loss by ionising radiation, chemotherapy, free radicals

Membrane damage by free radicals

Failure of membrane functional integrity due to damage to ion pumps

Blockage of metabolic pathways such as interruption of protein synthesis by diptheria toxin and respiratory poisons

Question 4

Define the term ‘free radicals’.

Answer 4

An atom or group of atoms containing one or more unpaired electrons.

Question 5

Name two free radicals.

Answer 5

Hydrogen peroxide

Superoxide anion

Question 6

What are the consequences?

Answer 6

Membrane breakdown
DNA damage
Protein cross-linking
Loss of enzymatic activity

Question 7

What are the two types of cell injury caused by ionising radiation?

Answer 7

Apoptosis and necrosis

Question 8

How do free radicals get generated?

Answer 8

Ultraviolet light
Drugs and chemicals
Inflammation
Ionising radiation

Question 9

Give three examples of antioxidants that reduce ROS.

Answer 9

Vitamin A & E - singlet oxygen
Catalase - hydrogen peroxide
Vitamin C - Superoxide radical

Question 10

What are the cell responses to injury?

Answer 10

Adaptation - adjusting their structure and functions for various conditions.

Reversible injury:
Hydropic degeneration (cloudy swelling) - accumulation of fluid to Na pump failure 
Fatty change - lipid accumulation due to ribosomal function failure 

Irreversible injury:
Necrosis
Apoptosis

Question 11

What is included in reversible injury? And give an example

Answer 11

Cellular swelling, large vacuoles in the cytoplasm 
Swelling of endoplasmic reticulum 
Swelling of mitochondria 
Disaggregation of ribosomes 
Chromatin clumping 
Cell blebs

Fatty liver can be reversed.

Question 12

What are the differences between necrosis and apoptosis?

Answer 12

Necrosis Apoptosis
Number
of cells group of cells single cells

Cell size Enlarged Reduced
Nucleus. Pyknosis etc. fragmentation
Plasma
Membrane. Disrupted. Intact

Cellular Enzymatic digestion.Intact
Contents
Inflammation. Frequent. None
Pathological. Physiological

Question 13

Describe what necrosis is.

Answer 13

Death of cells in living tissues characterised by the breakdown of the cell membranes, always a pathological condition.

Question 14

What are the nuclear changes seen in necrosis?

Answer 14

Pyknosis: smaller deeply basophilic stained nucleus due to clumping of chromatin.
Karyorrhexis: nucleus breaks up into many smaller fragments scattered in cytoplasm
Karyolysis: nucleus disappears

Question 15

What are the main types of necrosis?

Answer 15

Coagulative
General architecture well preserved
Nuclear changes
Most often results from interruption of blood supply

Liquifactive
Enzymatic liquefaction of necrotic tissue e.g. Necrosis in brain, pus formation in other tissues

Caseous
Dead cells persist as coarse granular eosinophilic debris
Shares features of coagulation and liquefaction necrosis
Most commonly seen in tuberculosis granuloma

Question 16

Give one example of coagulative necrosis.

Answer 16

Gangrene.

Question 17

What are the features of reversible and irreversible cell injury.

Answer 17

Reversible injury
Decreased ATP levels 
Ion imbalance 
Swelling 
Decreased pH
Fatty change 

Irreversible injury
Severe membrane damage 
Lysosomal rupture 
Extensive DNA damage (pyknosis, karyorrhexis, karyolysis) 
Cell lysis

Question 18

What is physiological and pathological apoptosis?

Answer 18

Physiological
Formation of digits from the limb buds (embryogenesis)
To maintain cell population in tissues
Immune cell development e.g deletion of autoreactive T-cells
To remove damaged cells by virus or radiation
Wound healing

Pathological
In tumour, apoptosis process is disturbed
Cell loss due to viral illness

Question 19

What are the causes of apoptosis?

Answer 19

Ionising radiation
Viral infection
Cell stress
Death receptors

Question 20

Define labile cells.

Answer 20

Proliferate continuously
Short life span
E.g. Epithelial cells, haemopietic cells

Question 21

Define stable cells

Answer 21

Conditional renewal of cells
Proliferate rapidly when cells are stimulated or lost
E.g. Liver, endocrine glands, bones

Question 22

Define permanent cells

Answer 22

Only proliferate during fetal life but not after birth

E.g. Neurons, cardiac muscle

Question 23

Define atrophy

Answer 23

Decrease in the size of an organ due to decrease in size of cells. Causes include: ageing, disuse of organs, malnutrition.

Question 24

Define hypertrophy

Answer 24

Increase in the size of an organ due to increase in size of cells. Causes include: excessive hormone stimulation, increased use.

Question 25

Define hyperplasia.

Answer 25

Increase in the size of an organ or tissue caused by an increase in the number of cells e.g. Glandular proliferation in the breast during pregnancy.

Question 26

Define metaplasia.

Answer 26

Replacement of one differentiated cell type by another e.g. Columnar replaced by squamous epithelium in the bronchus of smokers.

Question 27

Define aplasia.

Answer 27

It is a failure of cell production. E.g. during fetal development, aplasia results in absence of organ.

Question 28

Define hypoplasia.

Answer 28

Cell production that is less extreme than aplasia. E.g. Partial lack of growth and maturation of gonadal structures in Turner syndrome and klinefleter’s syndrome.

Question 29

What is autophagy?

Answer 29

Involves the degradation of a cells own components (damaged proteins, organelles or nuclear content) through the lysosomal machinery. Occurs within membrane-bound vesicles where lysosomal enzymes mix with substrates.

Question 30

What are the causes?

Answer 30

Starvation, oxidative stress, irradiation, accumulation of misfolded proteins.

Question 31

What are the three types of autophagy?

Answer 31

Macro-autophagy: the substrates are first packaged in an autophagosome and then this fuses with lysosome.
Micro-autophagy: here lysosome itself engulf the substrate.
Chaperone mediated autophagy: here receptors on the surface of lysosome selectively bind specific substances and allow them to be transported into lysosome.

Question 32

What are the two pathways for apoptosis?

Answer 32

Extrinsic: triggered by death receptors on the cell surface.

Intrinsic: initiated at the mitochondrial level.

Question 33

Apoptosis is not energy dependent. True or False?

Answer 33

False. Requires ATP.

Question 34

Describe what happens in the extrinsic and intrinsic pathways.

Answer 34

Intrinsic: Initiated within cells. Often activated in response to signals resulting from DNA damage, loss of cell survival factors, or other types of severe cell stress. Normally pro-apoptotic proteins are released from the mitochondria to activate caspase proteases and trigger apoptosis, without these the cell cannot die.

Extrinsic: begins outside the cell through activation of pro-apoptotic receptors on the cell surface. These are activated by molecules known as pro-apoptotic ligands. Binding causes receptors to cluster and ultimately form a death-inducing signalling complex (DISC). After this, the same effector caspase machinery is adopted.