Week 3 Pathology


  • Excess deposition of collagen and ECM in chronic disease (compared to breakdown)
  • Frustrated healing and chronic inflammation
  • Persistent stimulus (infection, autoimmune)
  • Macrophage/leukocyte activation
  • Growth factors – PDGF, FGF, TGF
    • proliferation of fibroblasts, endothelial cells and spec fibrogenic cells
    • activation of macrophages (IL4, IL 13, cytokines)–> attract monocytes, fibroblast activation and proliferation, increased collagen synthesis, inhibit metalloproteinases
  • Eg: cirrhosis, pulmonary fibrosis, chronic pancreatitis, constrictive pericarditis

Wound healing by primary / secondary intention.


Primary intention – when the incision is closed with sutures or glue

  •  24hrs -haematoma/scab formation,  epithelial cells move from wound edges and fuse in midline, neutrophil migration to edge of wound
  • Up to 3d – inflammation: neutrophils, leaky blood vessels–> oedema
  • 3-5 days – granulation tissue, neutrophils replaced by macrophages and fibroblasts enter(collagen laid), epithelial cells proliferate and thicken the epidermal layer
  • Day 5 – angiogenesis, incision filled with granulation tissue and epidermis recovers its original thickness.
  • 2 Weeks – continued accumulation of collagen fibres – decreased leukocytes, oedema and vasularity.
  • 1 month – wound contraction(myofibroblasts), connective tissue remodelling, scar is made of connective tissue devoid of inflammatory infiltrate. Intact epidermis.
  • Recovery of tensile strength – 10% at 1 week, 70-80% at 3months.

Secondary intention – when the wound is left open and allowed to heal naturally

  • Epithelialisation and contraction
  • Same steps but slower and more likely to have a larger scar and possibly hypertrophic scaring.


Factors influencing healing.

Local Systemic
Poor wound approximation Malnutrition
FB Diabetes
Infection Sepsis
Poor blood supply Smoking
Denervation Immunosuppression
Necrotic tissue Hypoxia
Mobility at site Anaemia
Tissue type Vitamin deficiency
Necrotic tissue Old age


Pathological aspects of wound repair.

  • Hypertrophic scars – within boundary of original scar but can be red, raised and pruritic – often self resolves
  • Keloid scars – go beyond original scar, more common in dark skinned people, needs treatment with steroids, surgery etc.
  • Chronic wounds – require debridement, irrigation and healing by secondary or tertiary intention.


  • Formation of new blood vessels in the adult
  • Endothelial progenitor cells from marrow
  • Branching and growth of existing vessels
  • Vasodilation
  • Proteolytic degradation of basement membrane
  • Endothelial migration to angiogenic stimuli
  • Maturation
  • Capillary formation
  • Recruitment of periendothelial cells for support structure.
  • Examples
    • Wound healing, growth
    • Hypertrophy eg skeletal muscle or uterus in pregnancy.
    • Tumours.

Overview of cell cycle


  • G0 – at rest, can be influenced by cytokines and growth factors/growth inhibitors to start G1
  • G1 – start of cycle, growth in mass, cetrosome duplication, restriction point, check point for dna damage before next stage
  • S – chromosome duplication
  • G2 – check point for dna faults or incomplete copying
  • M – mitosis
  • Labile tissues eg skin, GIT continuously cycle
  • Quiescent cells like hepatocytes can enter the cycle when required
  • Permanent cells eg neurons have lost their ability to proliferate



Collagen: Characteristics of different types

Collagen type Tissue distribution Genetic disorders
I Ubiquitous in hard and soft tissues Osteogenesis imperfecta, Ehlers- Danlos
II Cartilage, Intervertebral discs, vitreous Achondrogenesis
III Hollow organs, soft tissue Ehlers – danlos
IV Basement membrane Alport syndrome
V Soft tissue, blood vessels Ehlers Danlos

Other constituents of extracellular matrix

  • Proteoglycan
  • Laminin
  • Elastin
  • Hyaluronan
  • Glycoproteins