Robbins 7th ed - Chapter 3 - Tissue Renewal & Repair (2)

Question 1

Name the five phases of the cell cycle.

Answer 1

G0 – Permanent, non-dividing state
G1 – Quiescent, stable state, presynthetic
S – DNA synthesis
G2 – DNA checks, premitotic
M – Mitosis

Question 2

Name the three categories of cells based on their cell cycle activity.

Answer 2

Permanent, non-dividing cells: e.g. neurons, skeletal muscle, cardiac muscle.
Quiescent, low-level dividing cells that can undergo rapid divisions in times of need: e.g. liver, kidney, fibroblasts, smooth muscle, endothelial cells
Labile, continuously dividing cells: e.g. epithelial cells, bone marrow hematopoietic cells.

Question 3

How does skeletal muscle regenerate after injury?

Answer 3

Skeletal muscle cells themselves are terminally differentiated and do not divide. If they are lost in injury, they are replaced by satellite cells which are a stem cell pool in adult muscle.

Question 4

What is the process by which the liver regenerates after partial hepatectomy, assuming healthy liver tissue?

Answer 4

Mature hepatocytes replicate to regenerate the lost tissue. There is no stem cell involvement, unless there is fulminant hepatic failure, in which case the liver stem cells (which reside in the canals of Hering) can differentiate into either hepatocytes or biliary epithelial cells.

Question 5

What type of collagen is most of the collagen in skin and bone?

Answer 5

Type I

Question 6

What type of collagen is most of the collagen in cartilage?

Answer 6

Type II

Question 7

What type of collagen is most of the collagen in basement membranes?

Answer 7

Type IV

Question 8

Name some of the families of cell adhesion molecules.

Answer 8

Cadherins, Integrins, Selectins, Fibronectin, Laminin.

Question 9

Briefly describe hyaluronan.

Answer 9

Hyaluronan is a component of the ECM. It is a huge molecule with many disaccharide repeats. It serves as a ligand for cell surface receptors and other core proteins. It binds large amounts of water, giving the ECM its turgor and ability to resist compression.

Question 10

What is the difference between “regeneration” and “healing”?

Answer 10

Regeneration involves restitution of tissue identical to that lost by injury. Healing is a fibroproliferative response that “patches” rather than restores a tissue.

Question 11

What is a scar? Which tissues avoid scar formation in injury?

Answer 11

A scar is a fibrous ECM deposition, produced during the repair of injuries that are unable to completely regenerate and restore to the original anatomy. Some tissues that may not form a scar after injury include bone after fracture, and superficial skin wounds.

Question 12

Name the four steps of scar formation, starting with tissue injury.

Answer 12

1 – Tissue injury
2 – Inflammation (migration of fibroblasts, macrophages)
3 – Formation of granulation tissue (incl. angiogenesis)
4 – Scar formation (collagen meshwork forms, connective tissue remodelling)

Question 13

What are the basic components of granulation tissue?

Answer 13

Fibroblasts, loose connective tissue, thin-walled leaky capillaries formed by angiogenesis.

Question 14

During scar formation in wound healing, when does collagen deposition start?

Answer 14

Fibroblasts begin laying down collagen at about day 3, after they have been recruited.

Question 15

Which proteins are used to degrade collagens and other ECM proteins?

Answer 15

Matrix metalloproteinases (so called because they are dependent on metal ions – e.g. zinc – for their activity), which is a large family of collagenases and stromelysins, capable of degrading multiple ECM proteins. Matrix metalloproteinases are produced by fibroblasts, neutrophils, macrophages and others.

Question 16

Name some factors that can impede tissue repair.

Answer 16

Diabetes, Infection, Nutritional deficiencies, Steroids, Foreign body, Poor perfusion, Local mechanical pressure/tension, Nature of tissues injured, etc.

Question 17

What is meant by the term “fibrosis”?

Answer 17

This refers to the same process of collagen deposition and other ECM components as in scar formation, except that it happens in excess and is pathologic. It is usually due to persistent injurious stimuli and chronic inflammation.

Question 18

What is the most important growth factor triggering the synthesis and deposition of ECM proteins during scar formation and fibrosis?

Answer 18

TGF-β

Question 19

Which type of collagen is laid down during healing by first intention in the skin

• initially?
• later?

Answer 19

Type III initially, and then later replaced by the stronger Type I.

Question 20

During healing by first intention, when is neovascularisation maximal?

Answer 20

Day 5

Question 21

Name as many cell types as you can that are capable of phagocytosis.

Answer 21

Monocytes, Macrophages, Neutrophils, Dendritic cells, Mast cells, Eosinophils.

Question 22

During healing of a clean wound by first intention, how much of original tissue strength is attained by:

• Day 7?
• 3 months?

Answer 22

Day 7: 10%

3 months: 80%

Question 23

Name the three phases of bone fracture healing.

Answer 23

1. Reactive phase
2. Reparative phase
3. Remodelling phase

Question 24

What happens in the reactive phase of bone fracture healing?

Answer 24

A haematoma forms, which attracts neutrophils and other inflammatory cells. This fibrin meshwork sets up a framework for the formation of procallus.

Question 25

Name the two processes that occur during the reparative phase of bone fracture healing.

Answer 25

1. Endochondral ossification: hyaline cartilage is replaced with lamellar bone.
2. Bony substitution: woven bone is replaced with lamellar bone.

Question 26

What happens in the remodelling phase of bone fracture healing?

Answer 26

The trabecular bone (which replaced the lamellar bone) is resorbed by osteoclasts, creating shallow pits (Howship’s lacuna), into which osteoblasts deposit compact bone.

Question 27

In bone fracture healing, what is callus made of?

Answer 27

Most commonly, callus is made of hyaline cartilage and woven bone, but not all callus contains cartilage.