Pathology 6: chronic inflammation + wound healing

Question 1

List 5 causes of chronic inflammation

Answer 1

Persistent infection (most common cause).
Infection with viruses, mycobacteria, parasites and fungi.
Autoimmune disease.
Foreign material.
Carcinoma.

Question 2

Name 3 chronic inflammatory cells

Answer 2

Lymphocyte.
Plasma cell.
Macrophage.

Question 3

Where do macrophages come from?

Answer 3

Macrophages are derived from stem cells in the bone marrow and circulate in the blood stream as monocytes. The half-life of a monocyte is about a day whereas macrophages can live in tissues for months to years.

Question 4

What is a granuloma?

Answer 4

A collection of activated macrophages/epithelioid histiocytes. Granulomas may be caseating or non-caseating ie. may show caseous necrosis or not.

Question 5

What is repair and when does it happen?

Answer 5

Repair is replacement of damaged tissue with a collagen rich or fibrous scar. This occurs when regenerative stem cells are lost or when the tissue which is injured lacks regenerative capacity eg. heart muscle which undergoes ischaemic necrosis.

Question 6

What is granulation tissue?

Answer 6

Granulation tissue formation is seen in the initial phase of repair and granulation tissue consists of proliferated capillaries (which provide nutrients) fibroblasts (which deposit type 3 collagen) and myofibroblasts (which mediate wound contraction).

Question 7

What are the layers of an ulcer?

Answer 7

The first layer of an ulcer contains neutrophils, fibrin, and red blood cells. Deep to this layer there is a layer of granulation tissue which comprises a proliferation of blood vessels and fibroblasts. These fibroblasts secrete collagen and the layer beneath the granulation tissue layer comprises predominantly fibroblasts with associated collagen representing scar tissue.

Question 8

List 5 important growth factors which are necessary for repair and their actions

Answer 8

Transforming growth factor (TGF) alpha. Epithelial cell and fibroblast proliferation.
TGF-beta. Fibroblast proliferation and inhibition of inflammation.
Platelet-derived growth factor (PDGF). Growth of endothelium, smooth muscle and fibroblasts.
Fibroblast growth factor (FGF). Angiogenesis.
Vascular endothelial growth factor (VEGF). Angiogenesis.

Question 9

What are the four phases of normal wound healing?

Answer 9

Normal wound healing processes can be divided into 4 overlapping phases:

Coagulation or clotting phase.
Inflammatory phase.
Proliferative phase or granulation tissue formation phase.
Remodelling phase.

Question 10

What happens in the coagulation and inflammatory phases of wound healing?

Answer 10

Blood-borne cells, that is neutrophils, macrophages and platelets play critical roles. These cells provide growth factors which are needed for recruitment of epithelial cells and connective tissue cells into the wound bed.

Question 11

What happens in the proliferative phase of wound healing?

Answer 11

The proliferative phase starts approximately 3 days after injury and is characterized by increased levels of epithelial and fibroblast proliferation and migration. There is also extracellular matrix synthesis in response to autocrine and paracrine growth factors and angiogenesis or new blood vessel growth. Because of the presence of blood vessels, the tissue has a granular appearance termed granulation tissue.

Question 12

What happens in the remodelling phase of wound healing?

Answer 12

Approximately 1 to 2 weeks after injury, myofibroblasts that are present within the granulation tissue begin to remodel the extracellular matrix which is followed by apoptosis of resident cells which leads to the formation of an acellular scar.

Question 13

What is the difference between wound healing by primary and secondary intention?

Answer 13

• In primary intention, wound edges are brought together with sutures which leads to minimal scarring
• In secondary intention, the edges are not brought together and granulation tissue will fill the gap and then myofibroblasts contract the wound in which case scar tissue will form.

Question 14

What is the difference between a keloid scar and a hypertrophic scar?

Answer 14

A hypertrophic scar is defined as excess production of scar tissue that is localised to the area of the wound.

A keloid scar is exuberant production of scar tissue that is out of proportion to the wound size. Keloids are associated with excess type 3 collagen deposition and are more common in black people. They often affect the ear lobes, face and upper extremities.

Question 15

Name one vitamin and two minerals which are important for wound healing and how these contribute to the wound healing process.

Answer 15

Vitamin C, copper and zinc.

Deficiencies of vitamin C and copper will delay healing as these two elements are involved in the formation of collagen crosslinks.

Zinc deficiency is also associated with poor wound healing as zinc is a co-factor for collagenase which is required to replace type 3 collagen with type 1 collagen.

Question 16

List 5 reasons other than mineral/vitamin deficiency for impaired wound healing.

Answer 16

Presence of foreign bodies.
Infection.
Poor blood supply.
Diabetes.
Malnutrition.

Question 17

Describe the pathogenesis of the 4 types of hypersensitivity reaction and give one example of a disease caused by each type.

Answer 17

• Type I reactions: immediate allergic reactions, caused by preformed IgE antibodies activating mast cells and basophils (eg. anaphylaxis, food or pollen allergies and asthma)
• Type II hypersensitivity reactions: (eg. autoimmune haemolytic anaemia (where red cells are the target) and pemphigus vulgaris (where desmosomes are attacked))
• Type III hypersensitivity reactions immune complex-mediated with tissue damage caused by antigen-antibody complex deposition (eg. SLE, glomerulonephritis and vasculitis)
• Type IV hypersensitivity reactions: delayed and cell-mediated and are the only hypersensitivity reaction that involves sensitized T-lymphocytes rather than antibodies (eg. RA, psoriasis and allergic contact dermatitis)

Question 18

Summarise the pathogenesis of autoimmune disorders.

Answer 18

• Autoimmune disorders are characterised by immune mediated damage to self-tissues and they involve a loss of self-tolerance
• The disorders are more common in women and it is thought that this may be due to the presence of oestrogen which is known to reduce apoptosis in B-cells allowing them to persist and to damage self
• The cause of autoimmune disease is likely to be an environmental trigger in genetically programmed people and they are clinically characterised by progressive disease with relapses and remissions
• The diseases often show overlapping features and this is partially explained by the idea of epitope spreading
• This means that the disease starts out with an autoimmune reaction to a single epitope and with time new B or T-cell reactions develop to other antigens.