Healing And Repair

Question 0

Understand and describe fibrous repair

Answer 0

1. Cell migration
2. Blood vessels - angiogenesis
3. Extracellular matrix production and remodelling
   Cell migration - inflammatory cells (phagocytosis, chemical mediators), endothelial cells (angiogenesis), fibroblasts/myofibroblasts (ECM proteins e.g. collagen, wound contraction)
   Angiogenesis - development of a blood supply is vital to wound healing, induced by VEGF, pre existing vessels sprout new vessels. Endothelial proteolysis of basement membrane, migration of endothelial cell via chemotaxis, endothelial proliferation, endothelial maturation and tubular remodelling, recruitment of periendothelial cells.
   Extracellular matrix - supports and anchors cells, separates tissue compartments, sequesters growth factors, allows communication between cells, facilitates cell migration, matrix glycoproteins, proteoglycans, elastin.
   Inflammatory cells infiltrate, clot replaced by granulation tissue, maturation, left with fibrous scar.

Question 1

Define the terms ‘resolution’, ‘fibrous repair’, ‘regeneration’, ‘labile, stable and permanent tissue’

Answer 1

Resolution - the disappearance of a symptom or condition
Fibrous repair - the replacement of functional tissue by scar tissue
Regeneration - the replacement of dead or damaged cells by functional, differentiated cells (derived from stem cells)
Labile tissue - normal state is active cell division, usually rapid proliferation e.g. epithelial
Stable tissue - resting state G0, speed of regeneration variable e.g. hepatocytes
Permanent tissue - unable to divide G0, unable to regenerate e.g. neurones, cardiac myocytes

Question 2

Understand and describe regeneration

Answer 2

Unipotent - can only produce one type of differentiated cell e.g. epithelia
Multipotent - can produce several types of differentiated cell e.g. haematopoietic
Totipotent - can produce any type of cell e.g. embryonic stem
Growth factors - promote proliferation in stem cells, extracellular signals transduced into cell, promotes expression of genes controlling cell cycle, proteins, hormones, autocrine
Contact between basement membrane and adjacent cells - signalling through adhesion molecules, inhibits proliferation in intact tissue, contact inhibition, loss of contact promotes proliferation, exploited in cancer.

Question 3

Describe the healing of a clean, incised skin wound

Answer 3

Healing by primary intention - incised wound, apposed edges, minimal clot/granulation tissue, epidermis regenerates, dermis undergoes fibrous repair, sutures out at 5-10 days.
A clean sutured wound - transition from granulation tissue to scar tissue, maturation of scar continues for up to 2 years, minimal contraction and scarring, risk of trapping infection (abscess)

Question 4

Describe the healing of a large skin defect

Answer 4

Healing by secondary intention (infarct, abscess, ulcer or any large wound) - unapposed wound edges, large clot dries to form a scab, epidermis regenerates from the base up, repair process produces much more granulation tissue
Open wound - produces more contraction to reduce volume of defect, produces a larger scar, takes longer

Question 5

Briefly describe the structure of collagen

Answer 5

Composed of triple helices of various polypeptide alpha chains.
Polypeptide alpha chains synthesised in ER, enzymatic modification steps include vitamin C dependent hydroxylation, alpha chains align and cross-link to form procollagen triple helix, soluble procollagen is secreted.
After secretion, procollagen is cleaved to give tropocollagen. Tropocollagen polymerises to form fibrils –> fibres.

Question 6

Discuss factors influencing the efficacy of healing and repair

Answer 6

Local factors - type, size, location of wound, apposition (lack of movement), blood supply, infection, foreign material, radiation damage
General factors - age, drugs (steroids) and hormones, dietary deficiency, general state of health (chronic diseases), general cardiovascular status

Question 7

Describe special aspects of healing and repair in various tissues

Answer 7

Cardiac muscle - fibrosis
Bone - callus formation
Liver - acute damage –> regeneration, chronic damage –> cirrhosis
Peripheral nerve - Wallerian degeneration (proximal degeneration, distal proliferation ~1 mm/day)
CNS - no regenerative capacity, glial cells proliferate –> gliosis
Smooth muscle - permanent tissues. Will be replaced by scar. Vascular smooth muscle has some limited regeneration.
Skeletal muscle - limited regenerative capacity due to satellite cells

Question 8

Briefly discuss examples of collagen synthesis defects

Answer 8

Vitamin C deficiency –> scurvy. Inadequate vitamin C dependent hydroxylation of alpha chains leads to defective helix formation. Lacks strength, vulnerable to enzymatic degradation.
Ehlers-Danlos syndrome - defective conversion of procollagen to tropocollagen.
Osteogenesis imperfecta - abnormal or decreased alpha polypeptides