HC9: Tissue injury and repair

Cell adaptations

All diseases are results of visible cell abnormalities. There are 4 kinds of cell adaptations:

• Hypertrophy
• Atrophy
• Hyperplasia
• Metaplasia

Hypertrophy:

Hypertrophy is an increase in size of cells, resulting in increase in the size of an organ. This typically occurs in non-dividing cells and can be:

• Physiologic: hormonal → for example uterus growth
  • During pregnancy, cells in the uterus increase in size → the amount of cytoplasm increases
• Pathologic: increased workload → for example cardiac hypertrophy due to hypertension or faulty valves

Hypertrophy has a specific mechanism:

1. Sensors on the outside of the cell sense mechanical stress
2. In the nucleus of the cell, transcription factors are activated
3. Signaling pathways to make more contracting proteins are activated
4. Because there are more elements, the cytoplasm becomes bigger
5. The efficiency of the cell increases

Atrophy:

Atrophy is a reduction in cell size, resulting in a decrease in the size of the organ. This also can be physiologic of pathologic:

• Physiologic: embryonic development or a postmenopausal uterus
• Pathologic: many causes

The main causes of atrophy are:

• Decreased workload
  • Mainly in muscles
• Denervation
  • For example 2nd motor neuron disorders
• Decreased blood supply
• Decreased nutrition
• Aging
  • For example involution → loss of hormonal stimulation
• Pressure
  • For example tumors

Hyperplasia:

Hyperplasia is an increase in the number of cells, resulting in an increase in the size of an organ. This typically occurs in dividing cells and can be:

• Physiologic: hormonal or compensatory
  • Compensatory hyperplasia: after liver resection, the liver can create new cells to grow back
• Pathologic: excess of growth factors
  • This can occur as an adaptation to stress

Pathologic hyperplasia is distinct from cancer, but it will constitute a fertile soil in which cancerous proliferation may eventually rise.

Metaplasia:

Metaplasia is a reversible change in which one differentiated cell is replaced by another type, for example:

• Columnar → squamous
  • In the cervix and anus
• Squamous → columnar
  • In the esophagus

The body is divided in an inside and an outside world. Between these "worlds", there are junctions, for example:

• Gastro-esophageal
• Recto-anal
• Ecto-endocervical

When cells in the inside world get exposed to particles from the outside world, they adapt using metaplasia. They transform into layered squamous epithelia with lots of cytoplasm. An example of where this occurs is in the lung of a smoker.

Cell death

Death is defined by an irreversible injury:

• Reversible injuries → lead to recovery
  • There isn't much visibility
• Irreversible injuries → result in death

1. Biochemical alterations → cell death
2. Ultrastructural changes
3. Light microscopic changes
4. Gross morphologic changes

Some injuries can lead to death if they're prolonged and/or severe enough:

• Adaptation → reversible injury → irreversible injury → death

Many things can cause cell injury:

• Hypoxia
  • Decrease in oxygen
• Physical agents
  • For example trauma
• Chemical agents
  • For example medication or alcohol
• Infectious agents
  • For example viruses
• Immunologic
  • For example auto-immune diseases
• Nutritional
  • For example vitamin deficiency
• Genetic
  • For example inherited defects

Reversible cell injury:

Reversible cell injury is very subtle and hardly visible. A cause for reversible cell injury is hypoxia:

1. There is an oxygen shortage in a cell
2. The cell becomes stressed  → the ER and mitochondria swell and chromatin starts clumping
3. Recovery

Irreversible cell changes:

Cell changes become irreversible after:

• Mitochondrial irreversible damage
• Irreversible membrane defects
• Lysosomal digestion

There are many forms of necrosis:

• Liquefactive necrosis: the brain is not capable of forming scars → in case of an infarction in the brain, cells die and leave a hole in the brain → this hole is filled with liquid
• Gangrenous necrosis: occurs in case of ischemia → body parts don't get enough blood
• Caseous necrosis: looks different from normal necrosis, but isn't special
  • It can occur after TBC

Fat necrosis: when fat dies, fat tissue cannot be replaced and becomes a white mass which looks like a tumor