Cell Injury (Reversible and Irreversible)

Question 1

List the cellular adaptations to stress

Answer 1

• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia

Question 2

What is atrophy

Answer 2

• Morphology: Shrinkage of cell size by loss of substance, organ shrinkage, occurs in combination with autophagy (consumption of own tissue)
• Effect: Gradually decline in effectiveness due to underuse
• Cause: Decreased protein synthesis, increased protein degradation

Question 3

What is hypertrophy

Answer 3

• Morphology: Increase in cell size beyond what is normal for that cell, more cellular organelles and cytoplasm, enlarged organ
• Effect: Overuse, increased burden cannot be compensated for
• Cause: Physiologic or pathologic, increased functional demand, growth factor stimulation and hormonal simulation

Question 4

What is hyperplasia

Answer 4

• Morphology: Enlargement of an organ or tissue
• Cause: Increased production rate cells, accompanied by hypertrophy
  Effect:
• Physiologic or pathologic, increased functional demand
• Development and maturation (bone growth), growth factor stimulation, hormonal simulation
• Pathologicalhyperplasiato significant abnormalities in organisation and cyto-morphology

Question 5

What is metaplasia

Answer 5

• Morphology: Adult cell type replaced by another cell / converted to another cell type
• Effect: New function dependent on cell type, initially beneficial as defence but other properties are lost and if persistent may predispose to malignant transformation of epithelium
• Cause: Differentiation of stem cells along a new pathway

Question 6

What are is and are the causes and morphology of cell injury

Answer 6

Injury
- Normal cell undergoes reversible injury and recovery
- When recovery doesn’t occur it undergoes irreversible progressive injury
Causes:
- Hypoxia (tissue), ischaemia (vessel), chemical agents, infectious agents
- Immunologic, genetic defects, nutritional imbalances
- Physical and ageing
Morphology:
- All stresses and injuries exert effects at molecular / biochemical level
- Cellular function may be long lost before cell death occurs
- Morphologic changes lag far behind both, ultrastructural (EM, minutes to hours) and light microscope (hours to days)

Question 7

What are light microscope changes (reversible)

Answer 7

Cell Swelling:
- Increase in cell size by increased fluid
- Hydropic change, vacuoles fail to stain, entire organ can be affected
- Loss of function of cell membrane Na-K pump
- Inability to maintain ionic and fluid homeostasis
Fatty Change:
- Presence of lipid vacuoles in cytoplasm (cells involved in fat metabolism)
- Cell nucleus displaced to periphery of cell, increased eosinophilic staining
- Caused by hypoxic, toxic or metabolic injury

Question 8

What are ultrastructural changes (reversible)

Answer 8

• Alterations of cell membrane
• Swelling of RER cristae and detachment of ribosomes
• Swelling of, and presence of small phospholipid-rich amorphous deposits in mitochondria
• Nuclear alterations with clumping of chromatin

Question 9

List the biochemical changes (reversible)

Answer 9

• ATP depletion
• Damage to mitochondria
• Loss of calcium homeostasis
• Free radical formation
• Oxidative stress
• Defects in membrane permeability
• Damage to DNA and proteins

Question 10

What occurs during ATP depletion (biochemical - reversible)

Answer 10

ATP Depletion
- ATP produced in mitochondria, +O2  (oxidative phosphorylation) and -O2 (glycolysis)
Causes: 
- Inadequate O2 supply
- Inadequate nutrient supply
- Mitochondrial damage
- Chemical (toxic) injury
- Ineffective ATP dependant pumps

Question 11

What happens when damage to mitochondria occurs (biochemical - reversible)

Answer 11

Causes:
- Hypoxia, toxins and radiation
Effect:
- Abnormal oxidative phosphorylation
- Depletion of ATP, formation of reactive oxygen species
- Formation of mitochondrial permeability transition pore (loss membrane potential+pH)
- Leakage of mitochondrial proteins in cytosol

Question 12

What happens when loss of calcium homeostasis occurs (biochemical - reversible)

Answer 12

• Ca2+ within cytosol about 10000 x lower than extracellular or Ca2+ within mitochondria or ER controlled by ATP dependant Ca2+ transporters
• Ischaemia and toxins can lead to increased cytosolic Ca2+
• Increased cytosolic Ca2+ activates enzymes

Question 13

What happens when free radical are formed (biochemical - reversible)

Answer 13

• Excessive accumulation of highly reactive oxygen-derived free radicals (ROS, NO)
• Attack nucleic acids, proteins and lipids
• Superoxide: Generated by ETC and converted to H2O2, hydroxyl free radical or peroxynitrite (ONOO-)
• Phagocyte Oxidase: Enzyme in phagosomes of leukocytes generates superoxide

Question 14

What happens when oxidative stress occurs (biochemical - reversible)

Answer 14

Effects:

• Injuries
• Lipid peroxidation of membranes (oxidative degradation oflipids)
• Cross-linking and changes in proteins and DNA damage

Question 15

What happens when defects in membrane permeability occurs (biochemical - reversible)

Answer 15

Causes:
- Ischaemia, free radicals
- Cytosolic Ca2+
- Microbial toxins, viral protein, complement components and chemicals
Effect:
- Direct damage to plasma membrane
- Mitochondrial / plasma / lysosome membrane damage

Question 16

What happens when damage to DNA and proteins occurs (biochemical - reversible)

Answer 16

• DNA proof reading enzyme (base excision)
• Inability to repair of double-strand breaks in DNA
• Proteasomal degradation

Question 17

What are irreversible changes to cells

Answer 17

• Mitochondrial irreversibility
• Irreversible membrane defects
• Lysosomal digestion
• Irreversible mitochondrial dysfunction
• Profound membrane disturbances