Cell Injury

Question 1

Define Hypoxia

Answer 1

A state of oxygen deprivation

Question 2

What are the four causes of hypoxia?

Answer 2

Hypoxaemic hypoxia
Anaemic hypoxia
Ischaemic hypoxia
Histocytic hypoxia

Question 3

What is Hypoxaemic Hypoxia?

Answer 3

Low arterial oxygen content
Possible causes:
- high altitudes
- reduced oxygen absorption due to lung disease

Question 4

What is Anaemic Hypoxia?

Answer 4

Deceased oxygen carrying ability of oxygen
Possible causes
- Anaemia
- CO poisoning

Question 5

What is Ischaemic Hypoxia?

Answer 5

Interruption to blood supply
Possible causes
- Blockage of a vessel
- Heart failure

Question 6

What is Histocytic Hypoxia?

Answer 6

The inability to use oxygen due to disabled oxidative phosphorylation enzymes
Possible causes
- cyanide poisoning

Question 7

Give examples of toxins that can cause cell injury

Answer 7

High concentration of oxygen - promotes free radical formation
Medicines - e.g. chemotherapy
Narcotic Drugs
Pollutants
Glucose and Salt in hyper-tonic solutions

Question 8

How can heat injure cells?

Answer 8

Heat can cause proteins to unfold. Cells exposed to heat release heat shock proteins which try to mend these misfolded proteins

Question 9

List some other causes of cell injury

Answer 9

Cold
Trauma
Radiation
Micro-organisms - e.g bacteria, viruses, fungi, parasites
Immune mechanisms - hypersensitivity, autoimmune diseases

Question 10

Explain hypersensitivity

Answer 10

overly vigorous immune reaction results in accidental destruction of host cells

Question 11

Explain Autoimmune diseases

Answer 11

Failure to distinguish self cells from non-self cells

Question 12

What are the principal structural targets for cell damage?

Answer 12

Plasma Membranes
Organelle Membranes - e.g. lysosomes
Nucleus - specifically DNA
Proteins - structural and enzymes
Mitochondria

Question 13

What are the features of reversible hypoxia?

Answer 13

Decreased ATP production which leads to:

• loss of activity of sodium potassium pump
• anaerobic respiration
• ribosomes detach from ER and protein synthesis is disrupted

Question 14

Explain the effects of loss of the sodium-potassium pump

Answer 14

Intracellular Na+ concentration rises
Water enters cell
Cell and organelles swell
Ca2+ enters and damages the cell components

Question 15

Explain the effects of anaerobic respiration

Answer 15

Build up of lactic acid
Decrease pH
Affects enzyme activity
Chromatin Clumping

Question 16

Explain the effects of the ribosomes detaching

Answer 16

Intracellular accumulation of fat, denatured proteins etc.

Question 17

What happens in irreversible hypoxia?

Answer 17

Development of profound disturbances in membrane integrity
Accumulation of cytosolic Ca2+ through entering the plasma membrane of damaged cells and by being released from intracellular stores

Question 18

What are the effects of increased cytosolic Ca2+?

Answer 18

Activates ATPase, further decreasing ATP concentration
Activates phospholipases resulting in more damage to the membrane
Activates proteases which breakdown the membrane and cytoskeleton
Activates endonucleases which damage DNA

Question 19

What is Ischaemic-Reperfusion Injury?

Answer 19

Blood flow returned to an ischaemic tissue that is not yet necrotic

Question 20

What are the effects of Ischaemic-Reperfusion Injury?

Answer 20

Increased production of oxygen free radicals
Increased neutrophils leading to more inflammation so increased tissue injury
Delivery of complement proteins and activation of the complement pathway

Question 21

How can free radicals cause cell injury?

Answer 21

Attack lipids in membrane, causing lipid peroxidation
Damage proteins and nucleic acids (i.e. mutagenic)
React with other molecules to make more free radicals

Question 22

What are free radicals?

Answer 22

Molecules with a single, unpaired electron
Important in cell signalling
Produced by leukocytes to kill bacteria

Question 23

Give three examples of free radicals

Answer 23

Hydroxyl (OH’)
Superoxide (O2-)
Hydrogen Peroxide (H2O2)

Question 24

Describe the three ways in which hydroxyl ions can be produced

Answer 24

Radiation - lyses water to OH’
Fenton reaction (uses Fe3+)
Haber-Weiss Reaction (uses superoxide and hydrogen peroxide)

Question 25

Define oxidative stress

Answer 25

Imbalance between free radical production and free radical scavenging

Question 26

What are the components of the anti-oxidant system?

Answer 26

SOD enzyme - catalyses superoxide into hydrogen peroxide
Catalases and Peroxidases - catalyse hydrogen peroxide into oxygen and water
Free Radical Scavengers
Storage Proteins

Question 27

Name some free radical scavengers

Answer 27

Vitamins A,C and E

Glutathione

Question 28

How do storage proteins work?

Answer 28

They sequester transition metals that catalyse the formation of free radicals

Question 29

Define oncosis

Answer 29

Cell death with swelling

Question 30

Define Necrosis

Answer 30

Morphological changes that follow cell death in living tissue

Question 31

Define Apoptosis

Answer 31

Cell death with shrinkage

Question 32

What changes that occur in cell injury are visible with a light microscope?

Answer 32

Cytoplasmic changes
Nuclear Changes
Abnormal intracellular accumulations

Question 33

What reversible changes are visible with an electron microscope?

Answer 33

Swelling of the cell and its organelles
Cytoplasmic blebs
Clumped Chromatin
Ribosome separation from ER

Question 34

What irreversible changes are visible with an electron microscope?

Answer 34

Further Cell Swelling
Nuclear changes - pyknosis, karyolysis and karyorrhexis
Swelling and rupture of lysosomes
Membrane defects
Appearance of myelin figures
Lysis of ER
Amphorous densities in swollen mitochondria