Basic Pathology

Question 1

What is hypertrophy?

Answer 1

An increase in cell size.

Question 2

What is hyperplasia?

Answer 2

An increase in cell numbers.

Question 3

What is atrophy?

Answer 3

A decrease in the size of cells.

Question 4

What is metaplasia?

Answer 4

A change in a cell from one type to another.

Question 5

What are the two main types of cell death?

Answer 5

Apoptosis

Necrosis

Question 6

What are the different patterns of necrosis?

Answer 6

• Coagulative necrosis: underlying architecture is preserved. This is characteristic of infarction (except in the brain).
  Liquefactive necrosis: the tissue becomes a viscous liquid. Characteristic of an infraction of the CNS.
  Gangrenous necrosis: usually refers to a limb that has undergone coagulative necrosis due to ischemia.
  Caseous necrosis: ‘cheese-like’ necrosis. Usually occurs with a tuberculosis infection.
  Fat necrosis: local area of fat destruction with saponification (white chalky areas).
  Fibrinoid necrosis: usually occurs where immune complexes are deposited in walls of blood vessels, producing a reaction in the vessel wall that appears like fibrin on H&E staining.

Question 7

Give examples of when apoptosis can be physiological.

Answer 7

During embryogenesis;
During normal cell turnover;
At the end of an immune response;
To remove self-reactive lymphocytes.

Question 8

Explain the intrinsic pathway of apoptosis.

Answer 8

The intrinsic pathway is responsible for apoptosis in most situations.
This occurs when mitochondrial membranes become permeable –> causing cytochrome C to leak into the cytoplasm –> activates caspases –> causes apoptosis. The permeability of mitochondria is closely regulated by BCL-2, which is produced in response to stimuli such as growth factors. It counteracts the pro-apoptotic Bax and Bak.
When the cell is deprived of growth factors –> BCL-2 decreases –> Bax and Bak become more active –> the Bax and Bak form channels in the mitochondrial membrane –> cytochrome C leaks out –> caspases activated –> apoptosis

Question 9

Explain the extrinsic pathway of apoptosis.

Answer 9

Cells can express death receptors on their surface, and binding of ligands for these receptors can trigger apoptosis. For example, Fas ligand binding to Fas –> activates caspases –> apoptosis.

Question 10

How does hypoxia cause cell injury?

Answer 10

Lack of oxygen supply –> failure of oxidative phosphorylation –> insufficient production of ATP –> failure of energy-dependent cell processes:

(1) Failure of Na-K-ATPase –> Na accumulates in the cell and there is K efflux.
(2) There is an attempt to increase ATP production by anaerobic glycolysis –> but his leads to a build-up of lactic acid –> decreases intracellular pH –> decreases activity of many essential enzymes.
(3) Ribosomes detach from the endoplasmic reticulum –> failure to synthesize protein
(4) Irreversible damage to mitochondrial membranes

Question 11

Explain oxidative stress.

Answer 11

Oxidative stress occurs when reactive oxygen species (have an unpaired electron in their outer orbit, which makes them unstable and reactive with other molecules) are increased. They are produced normally, but this production can be increased when, for example, there is inflammation or exposure to radiation. The cell has mechanisms to remove the ROS, such as glutathione, but if this is overcome, the ROS lead to damage: (1) attack cell membranes; (2) cross-link proteins; (3) damage DNA.

Question 12

What are the clinical features of acute inflammation?

Answer 12

• Redness
• Heat
• Swelling
• Pain
• Loss of function

Question 13

Outline the process of acute inflammation.

Answer 13

(1) Vascular events:
- Dilation of arteries and capillaries with increased blood flow to the site.
- Increased blood vessel permeability, mostly in venules.
(2) Cellular events:
- Neutrophils undergo: margination, rolling and adhesion to the vessel wall –> migrate between endothelial cells –> chemotaxis to the site of inflammation –> phagocytose pathogens and dead cells.

Question 14

What are the 4 possible outcomes of acute inflammation?

Answer 14

• Resolution
• Healing by scar formation
• Progression to chronic inflammation
• Tissue destruction leading to death

Question 15

What are the microscopic features of acute inflammation?

Answer 15

There is a mix of tissue destruction and healing.
Inflammatory cells are mostly macrophages (rather than neutrophils as in acute inflammation).
There can also be lymphocyte and eosinophils.

Question 16

Describe the process of healing by primary intention.

Answer 16

In the first 24 hours, there is acute inflammation and the defect fills with a clot/scab.
By day 3, the neutrophils are being replaced by macrophages; the clot is progressively digested by the phagocytes and granulation tissue is starting to form. Collagen is deposited.
By day 5, the wound is filled with granulation tissue and collagen is abundant.
By 2 weeks, the tissue becomes less vascular, with fibroblasts and collagen abundant.
Within 1 month, there is development of a narrow scar and the tensile strength of the skin is regained.

Question 17

Outline the process of healing by second intention.

Answer 17

When there is a large wound healing by first intention may not be possible. Healing by second intention is characterised by:

• More pronounced inflammation
• Granulation tissue progressively fills the defect
• There is contraction of the wound
• Loss of specialised structures in the skin, such as sweat glands

Question 18

What are the causes of chronic inflammation?

Answer 18

• Persistent infections
• Persistent exposure to toxins
• Autoimmune disease
• Repetitive bouts of inflammation and healing