5 Tissue Injury & Repair

Question 1

Tissue Injury & Repair

Answer 1

Why is it important to learn about tissue injury and repair?
What is homeostasis?
What is tissue injury?
What are the various responses to tissue injury?
What are some common causes of tissue injury?
What are the mechanisms of tissue injury?
What is tissue regeneration, repair, and fibrosis?
What is involved in the sequence of healing?
What factors influence repair?
What complications may arise from repair?

Question 2

Why Important?

Answer 2

To help avoid injuries in the clinical environment

To minimise damage when there is injury

To help facilitate repair

To monitor repair

To recognise complications of repair

Question 3

Introduction

Answer 3

Homeostasis

Injury

Excessive physiologic stresses or adverse pathologic stimuli 
Adaptation
Reversible injury
Irreversible injury + cell death

Question 4

Cellular Adaptation

Answer 4

Increased demand/stimulation  hypertrophy, hyperplasia
Decreased nutrients/stimulation  atrophy
Chronic irritation  metaplasia

Question 5

Cellular Injury

Answer 5

Acute and transient stimuli 
	e.g. hypoxia, chemical injury, microbial infection
 Reversible injury
 Irreversible injury  cell death
Apoptosis
Necrosis

Question 6

Causes of Cellular Injury

Answer 6

Hypoxia

Physical agents

Chemical agents

Infectious agents

Immunologic reactions

Genetic derangements

Nutritional imbalances

Question 7

Mechanisms of Cellular Injury

Answer 7

ATP depletion

Mitochondrial damage

Increased intracellular Ca2+

Oxidative stress

Membrane damage

DNA and protein damage

Question 8

Tissue Regeneration & Repair

Answer 8

Regeneration: complete reconstitution
Tissues with high proliferative capacity
Requires viable stem cells and intact connective tissue scaffolding
Repair: combination of regeneration and scar formation
Relative contribution of two processes depends on capacity to regenerate, extent of injury, and extent of scarring/fibrosis

Question 9

Mechanisms of Regeneration

Answer 9

Amphibians versus Mammals

Limited examples of true regeneration
Epithelium following superficial skin injury
Bone following fracture

Mostly compensatory
Hypertrophy (e.g. nephrons following nephrectomy)
Hyperplasia (e.g. hepatocytes following partial hepatectomy)

Question 10

Healing by Repair, Scarring, Fibrosis

Answer 10

Severe tissue injury with damage to parenchyma and stroma

Fibro-proliferative response
Deposition of collagen and ECM components (scar)
“Patches” tissue

Persistent damage  chronic inflammation  fibrosis

Question 11

Sequence of Healing

Answer 11

Inflammation

Angiogenesis/Neovascularization

Migration and proliferation of parenchymal cells and fibroblasts

Scar formation

Connective tissue remodeling

Question 12

Factors Affecting Wound Healing

Answer 12

Local Factors
Size
Location (i.e. how well vascularised)
Type (infectious/necrotic/traumatic)
Infections, mechanical forces, foreign bodies delay healing

Systemic Factors
Nutritional status
Metabolic status (e.g. diabetes mellitus)
Circulatory/vascular status
Hormones (e.g. glucocorticoids)

Question 13

Complications of Repair

Answer 13

Deficient scar formation

Excessive repair
Excessive granulation tissue (proud flesh)
Excessive collagen accumulation  hypertrophic scar
Keloid

Formation of contractures

Question 14

Summary

Answer 14

Tissue injury and repair is a vast but important topic to understand
Response to tissue injury involves both cellular and vascular responses
The aim of repair is to clear dead tissue and restore function as much as possible
Where normal tissue architecture cannot be restored, it is mostly replaced by fibrous tissue
The essential steps of repair are similar for all tissues but the outcomes can vary
A number of local and systemic factors affect the speed and outcome of repair
There may be complications of repair