Week 1 Pathology

Cell Injury

  • Causes of cell injury
    • ischaemia, toxins, infection, immune reactions, trauma, temperature extremes, genetic defects,
  • Sequence of events & appearances in reversible cell injury / irreversible cell injury / necrosis.
  • Reversible injury Irreversible injury
    Cell returns to normal if damaging stimulus is removed Cell will die
    Reduced oxidative phosphorylation –>ATP depletion–>failure of Na/K ATPase pump–> loss of cell membrane integrity –>cellular swelling(ion conc changes)Increased CA2+ intracellularly–> membrane and DNA damage

    Defects in protein synthesis–>cytoskeletal damage–>DNA damage

    Swelling of ER, loss of ribosomes, membrane blebs

    Irreversible mitochondrial injuryProfound membrane disturbance  and loss of integrity.

    Lysosomes rupture and digest cellular content, swollen mitochondria,

    Accumulation of reactive O2 species

    nuclear condensation, fading and fragmentation.

    Cell death

Free radical and chemically-induced injury.

  • Membrane lipid peroxidation
  • DNA fragmentation
  • Protein cross-linking and fragmentation.

Types of necrosis

  • Coagulative – architecture preserved eg MI
  • Liquefactive – liquid viscous mass – in brain hypoxic death, post bacterial infection
  • Caseous – white, granulomatous, no architecture – TB
  • Gangrenous – from infection
  • Fat necrosis – in pancreas
  • Fibrinoid – Ag-Ab mediated

Necrosis and Apoptosis

Feature Necrosis Apoptosis
Cell size Swelling Shrinks
Nucleus Fades–> shrinks and fragments Fragments into nucleosome size
Plasma membrane Disrupted Intact
Cellular content Enzymatic digestion, leakage out of cell, myelin figures Intact
Adjacent Inflammation None
Role Pathologic Physiologic or pathologic(DNA damage)


  • Hypertrophy – increase in cell size due to synthesis of more structural components – hypertrophic cardiomyopathy, post exercise, uterine in pregnancy.
  • Hyperplasia – increase in cell number – endometrial(DUB), breast in lactation, BPH
  • Atrophy – decrease in size of a cell due to decrease in cell substance. (disuse, denervation, decreased nutrients/blood supply, hormonal withdrawal, pressure) – eg muscle atrophy post fracture or denervation. Post menopausal vaginal atrophy.
  • Metaplasia – reversible change in adult cell type – eg barrett’s oesophagus – lining changes from stratified squamous to glandular columnar
  • Cell death – loss of function and existence of a cell.
  • Necrosis – cell death that occurs after abnormal stresses and is always pathological
  • Apoptosis – programmed cell death due to activation of internal suicide program, no inflammation
  • Ischaemia – loss of blood supply from impeded arterial flow or decreased venous drainage in a tissue. So affects O2 as well as other metabolic substrates.
  • Hypoxia – deficiency of oxygen
  • Reperfusion Injury – When reperfused tissues sustain loss of cells in addition to the cells that are irreversibly damaged at the end of ischaemia. Injury by reactive O2 and N species due to damaged mitochondria, inflammation due to chemotaxis causing further injuries, activation of complement.