Chapter 2: Cellular Responses to Stress and Toxic Insults

Question 1

Define cell injury.

Answer 1

Cell injury occurs when a pathological stimulus exceeds the capability of the adaptive response.
It is reversible to a point, but then progresses to irreversible cell injury and then to cell death.

Question 2

What are the two types of cell death?

Answer 2

Necrosis and apoptosis.

Question 3

Define an adaptation.

Answer 3

Adaptations are reversible functional and structural responses to a physiologic state (eg. pregnancy) or a pathological stimulus.

Adaptive responses may include hypertrophy, hyperplasia, metaplasia or atrophy.

Question 4

Discuss hypertrophy.

Answer 4

Hypertrophy is cell enlargement with increasing the number of cells. It involves increased production of cellular proteins.

It usually occurs in response to increased workload (eg. skeletal muscle, myocardium) but can also occur in response to hormone effects (eg. uterus during pregnancy).

Question 5

Discuss hyperplasia.

Answer 5

Hyperplasia is the increase in the number of cells in a tissue in response to a stimulus.

Hyperplasia can physiologic or pathologic, and occurs due to growth factors or hormones driving mature cell proliferation. Rarely it can stimulate stem cells division.

Question 6

Discuss atrophy.

Answer 6

Atrophy is the reduction in the size of an organ or tissue due to decreased cell size and/or number.

Causes include decreased workload (eg. due to disease), denervation, ischaemia, inadequate nutrition (eg. cachexia), loss of endocrine stimulation (eg. menopause) or due to pressure.

Cellular atrophy is often reversible, as the reduced metabolic demands allow it to survive in a new equilibrium. However atrophy can be a precursor to cell death (eg. in the setting of ischaemia).

Question 7

What is the mechanism of atrophy?

Answer 7

Atrophy results in reduced protein synthesis and increased protein degradation.

Cellular protein degradation occurs via the ubiquitin-proteasome pathway, in which ubiquitins ‘tag’ proteins for destruction by proteasomes.

Often there is also a degree of autophagy.

Question 8

Define metaplasia.

Answer 8

Metaplasia is a reversible change in which one differentiated cell type is replaced by another. Examples include Barrett’s and smokers’ respiratory epithelium.

It is important to note that metaplasia does not terminally differentiated cells to change their phenotype, but rather reprograms stem cells to pursue an alternative differentiation pathway.

Question 9

What are the characteristics of reversible cell injury?

Answer 9

• Reduced oxidative phosphorylation with depletion of ATP stores
• Cellular swelling due to loss of ion and water balance across the membrane.

Question 10

What are the morphologic features of cell injury?

Answer 10

REVERSIBLE CELL INJURY

• cell and organelle swelling
• mitochondrial swelling
• fatty change
• blebbing of the plasma membrane
• dilatation of the endoplasmic reticulum
• clumping of nuclear chromatin
• eosinophilia (due to reduced cellular RNA)

NECROSIS

• eosinophilia
• nuclear shrinkage, fragmentation and dissolution
• breakdown of plasma membrane and organelle membranes
• abundant myelin figures
• leakage and enzymatic digestion of cellular contents

Question 11

What are the different patterns of necrosis?

Answer 11

• Coagulative necrosis. Architecture of dead tissue is preserved temporarily. Classically seen following ischaemia due to vascular obstruction. Virtually all ‘infarcts’ except in the brain.
• Liquefactive necrosis. Digestion of dead cells by enzymes. Examples include focal bacterial and fungal infection with formation of pus, and infarcts in the central nervous system.
• Caseous necrosis. Usually seen in focal tuberculous infection. Cheese-like areas filled with disorganised cells and debris.
• Fat necrosis. Due to necrosis of fatty tissue classically in setting of acute pancreatitis. Triglycerides are split into fatty acids that then undergo saponification with calcium.
• Fibrinoid necrosis. Specialised form of necrosis seen in vasculitides.

Question 12

List the mechanisms and biochemical pathways of cell injury.

Answer 12

• ATP depletion
• mitochondrial damage
• influx of calcium and loss of calcium homeostasis
• accumulation of oxygen-derived free radicals (oxidative stress)
• defects in membrane permeability
• damage to DNA and cell proteins

Figure 2-16