Cell Injury And Death 1

Question 1

Why does cell injury arise?

Answer 1

Severe changes in environment = cell adaptation, injury or cell death
Depends on type, severity, duration and tissue type

Question 2

Response to injury

Answer 2

Adaptation —> injury (reversible) —> death (necrosis/apoptosis)
But can result in structural and functional changes

Question 3

Cardiac myocytes response to cell injury (hypertension)

Answer 3

Increase workload (vascular resistance)
Hypertrophy
Increased weight and size of heart
- workload is still too high
- additional stress (atherosclerosis?)
Cell injury and death (Myocardial Infarction)

Question 4

Causes of cell injury

Answer 4

Hypoxia (deprivation of oxygen)
Toxins - drugs, O2
Physical agents - trauma, temperature, pressure, electric currents
Radiation
Microorganisms
Immune mechanisms 
Nutrition/diet - excess/deficiency 
Genetic and aging process

Question 5

Types of hypoxia (HAIH)

Answer 5

Hypoxaemic - arterial oxygen content is low (high altitude/reduced absorption - lung disease)
Anaemic - Haemoglobin cannot carry O2 effectively (anaemia/carbon monoxide poisoning)
Isachaemic - interruption to blood supply (blockage/heart failure)
Histiotoxic - inability to utilise oxygen (oxidative phosphorylation fails - cyanide poison)

Question 6

What things are toxic?

Answer 6

Glucose and salt in hypertonic solution
Poison
High oxygen 
Pollutant
Insecticides/pesticides/herbicides
Asbestos
Alcohol
Drugs
Medicine

Question 7

Immune system damage

Answer 7

Hypersensitivity - overly vigorous immune response, host tissue injured (hives)
Autoimmune - cannot distinguish between self and non self (attacks own cells eg Hashimotos)

Question 8

Cell components susceptible to injury

Answer 8

Cell membranes - plasma and organelle
Nucleus - DNA
Proteins - structural and enzymes
Mitochondria - oxidative phosphorylation (ATP affected)

Question 9

Low ATP effects on cell (reversible)

Answer 9

Mitochondria attacked:

Loss of ATP production via oxidative phosphorylation:

Na pump cannot work = influx of sodium water and calcium,
potassium leaks out (oncosis/swelling, loss of microvilli, blebs, ER swell, myelin figures)

Increased glycolysis = increase lactic acid - lower pH and glycogen (chromatin clump proteins denature)

Detachment of ribosomes = decreased protein synthesis, lipid deposition

Question 10

Influx of calcium effects

Answer 10

Activation of:
ATPase - lower ATP
Phospholipase - decreased phospholipids
Protease - membrane and cytoskeleton disrupted
Endonuclease - nuclear chromatin damaged

Question 11

Free radicals

Answer 11

ROS/RNS
Single unpaired electron in outer shell
Unstable - react with other molecules and produce further free radicals

Question 12

Free radical examples

Answer 12

Superoxide (O2-)
Hydrogen peroxide (H2O2)
Hydroxyl radical (OH)

Question 13

How are free radicals formed

Answer 13

Metabolism (ETC chain)
Radiation
Transition metals (Fenton reaction iron)
Drugs and chemicals (paracetamol metabolism, p450 system)
Inflammatory response - respiratory burst/oxidative burst

Question 14

What do free radicals injury

Answer 14

Lipids - peroxidation damage membrane
Proteins - oxidation side chains/backbone, cross links, fragmentation
DNA - reaction with thymine, single strand breaks, mutagenic and carcinogenic

Question 15

Bodies control of free radicals

Answer 15

Spontaneously decay

Free radical scavengers - vitamin ACE, metal carrier/storage proteins (transferrin)

Enzymes - superoxide dismutase (superoxide to hydrogen peroxide), catalase (hydrogen peroxide to water and oxygen), glutathione peroxidase

Question 16

Body’s control of free radical damage (proteins)

Answer 16

cross link of proteins = fragmentation
Protein chaperones help folding

Heat shock proteins (hsp70/90) - mend misfolded proteins, maintain cell

Question 17

Injured and dying cells change in appearance: (light microscope)

Answer 17

Cytoplasm - less pink from oncosis (swelling of water)

Nuclear changes (pyknosis - shrink, karyorrhexis - fragment, karyolysis - disappear)

Abnormal cellular accumulations

Question 18

Electron microscope appearance of dying and injured cells:

Answer 18

reversible - blebs, swelling, ribosomes dispersed, ER/mitochondria swelling, clumping of chromatin, autophagy lysosomes

Irreversible - rupture of lysosomes and autolysis, defects in cell membrane, myelin figures, lysis of ER, nuclear changes

Question 19

Oncosis

Answer 19

Cell death with swelling (prior to death)

Question 20

Necrosis

Answer 20

Morphological changes that occur after a cell has died (12-24 hours)
Can be:
- coagulatative
- liquefactive
- caseous
- fat
- fibrinoid

Question 21

Apoptosis

Answer 21

Programmed cell death

Question 22

Coagulation necrosis

Answer 22

Protein denaturation
Solid organs
Cell architecture preserved

Question 23

Liquefactive necrosis

Answer 23

Enzyme release
Loose tissues
Many neutrophils (infection)
Digestion of tissues

Question 24

Caseous necrosis

Answer 24

Cheese like
Contains structures debris
Infection (TB especially)

Question 25

Fat necrosis

Answer 25

Form chalky deposits
Usually occurs in pancreatitis - releases lipases, FA are released, form calcified deposits
Adipose blobs on slide