Cell Injury

Question 1

List four possible causes of cell injury and death.

Answer 1

Hypoxia

Toxins

Physical agents - direct trauma, extremes of temperature, changes in pressure, electric currents.

Radiation

Micro-organisms

Immune mechanisms

Dietary insufficiency and deficiencies, dietary excess.

Question 2

What is hypoxia?

Answer 2

Hypoxia is when the body or some tissue within the body is deprived of oxygen.

Question 3

What are the causes of hypoxia?

Answer 3

Hypoxaemic hypoxia - arterial content of oxygen is low.

Anaemic hypoxia - decreased ability of haemoglobin to carry oxygen.

Ischaemic hypoxia - interruption to blood supply.

Histotoxic hypoxia - inability to utilise oxygen in cells due to disabled oxidative phosphorylation enzymes.

Question 4

List four toxins.

Answer 4

Glucose and salt in hypertonic solutions

High concentration of oxygen

Poisons

Pollutants

Insecticides

Herbicides

Asbestos

Alcohol

Narcotic drugs

Medicines

Question 5

Where are the principal structural targets for cell damage?

Answer 5

Cell membranes - plasma membrane, organelle membranes

Nucleus - DNA

Proteins - structural, (enzymes)

Mitochondria - oxidative phosphorylation

Question 6

List three free radicals that are of particular biological significance in cells.

Answer 6

OH. (Hydroxyl) - the most dangerous

O2- (superoxide)

H2O2 (hydrogen peroxide)

Question 7

How are free radicals removed from our bodies?

Answer 7

Spontaneous decay

Enzymes - superoxide dismutase (SOD) - produces H2O2 which is less toxic to cells.

Also, catalases and peroxidases complete process of removal: H2O2 to O2 and H2O.

Free radical scavengers - vit E, A and C

Question 8

What happens to the morphology of cells when they are damaged/die?

Answer 8

Detachment and loss of ribosomes and accumulation of denatured proteins. Nuclear changes - clumped chromatin - very subtle (reversible) followed by various combinations of pyknosis (shrinkage), karryohexis (fragmentation) and karryolysis (dissolution) (irreversible).

Question 9

What is pyknosis?

Answer 9

Shrinkage

Question 10

What is karryohexis?

Answer 10

Fragmentation

Question 11

What is karryolysis?

Answer 11

Dissolution

Question 12

What are abnormal accumulations which respect to cell injury and cell death?

Answer 12

Abnormal accumulations in reversibly injured cells reflect damaged proteins and accumulation of abnormal metabolites.

E.g. Mallory’s hyaline, seen in alcoholic liver disease - accumulation of altered keratin filaments.

Question 13

Define oncosis.

Answer 13

Spectrum of changes in injured cells prior to death. - process of death.

Question 14

Define necrosis.

Answer 14

Morphological changes that follow cell death in living tissue, largely due to progressive degradative action of enzymes on lethally injured cell.

Question 15

Define apoptosis.

Answer 15

Cell death induced by regulated intracellular program - cells activate enzymes that degrade cells’ own nuclear DNA and proteins. Cell suicide.

Question 16

List the different types of necrosis.

Answer 16

Two main types: coagulative and liquefactive.

Two other special types: caseous (TB) and fat necrosis.

NB. Gangrene and infarct are clinical terms - NOT types of necrosis.

Question 17

Where are you most likely to see liquefactive necrosis?

Answer 17

In the brain because it is a fragile tissue without support from a robust collagenous matrix.

Question 18

Where is fat necrosis most typically seen?

Answer 18

Pancreas as a consequence of pancreatitis.

Pancreatitis causes release of lipases from injured pancreatic acinar cells. Lipases act on fatty tissue of pancreas and fat elsewhere in the abdominal cavity causing fat necrosis.

Question 19

What is gangrene?

Answer 19

Gangrene is a clinical term for necrosis that is visible to the naked eye.

Question 20

What are the different types of gangrene?

Answer 20

Dry- coagulative necrosis

Wet - liquefactive necrosis typically due to infection.

NB. Everyone has had gangrene….remnant of the umbilical cord in a newborn.

Question 21

What type of necrosis is typically associated with tuberculosis?

Answer 21

Caseous

Question 22

Briefly describe the two pathways of apoptosis initiation.

Answer 22

Intrinsic - (cell stress pathways) p53 activation, cytochrome C release from mitochondria. Combines with APAF1 and caspase 9. Forms an apoptosome. This activates downstream caspases.

Extrinsic - (death receptor pathway) death ligands TRAIL & FAS bind receptors, activating procaspase 8, which activates downstream caspases.

Question 23

What is the pathway of paracetamol metabolism? What happens when glutathione runs out?

Answer 23

Question 24

What happens in a paracetamol overdose?

Answer 24

After an overdose, glutathione is depleted and NAPQI binds with sulphydryl groups on liver cell membranes, eventually causes hepatocyte necrosis and liver failure.

Some people have lower reserves of glutathione and paracetamol OD is more dangerous.

Question 25

What is the antidote to a paracetamol overdose?

Answer 25

N-acetylcysteine - increases availability of hepatic glutathione.

Question 26

When does cell damage become irreversible?

Answer 26

Increased calcium concentrations inside the cell causes enzymatic activation which leads to downstream processes (acting as a secondary messenger) that results in irreversible death (phospholipases, ATPases, proteases and endonucleases).

Question 27

Describe the mechanisms that result in cell injury as a result of ischaemia.

Answer 27

Lack of oxygen due to ischaemia results in lack of ATP (due to decreased oxidative phosphorylation) hence the Na-K+-ATPase pump on cell membranes cannot function so cell becomes depolarized ~ reversal of NCX so influx of Ca2+. Also get altered protein synthesis. Due to decreased ox-phos - increased glycolysis (increased lactic acid) - decreases pH - chromatin clumping.