5.1

• Growth


  Increase in size and mass (volume) of individuals, organs, cells, sub-cellular organelles
• Differentiation


  An unspecialised cell becomes specialised, undifferentiated → differentiated
• Maturation


  A differentiated cell has specific structures and performs specific functions
• Normal growth & differentiation

  1. Haploid gametes fuse to form diploid zygote (totipotent cell)

  2. Zygote undergoes replication by mitosis to form multi-cellular organism (growth)

  3. Replicative proliferation of cells accompanied by differentiation to mature and produce many different types of somatic cells
• Genome & gene expression

  Human genome contains ~20,000 protein-coding genes, different patterns of genes expressed in different cell types, tissues, developmental stages or diseases
• Abnormalities of growth and differentiation can occur at any stage of embryological development
• Abnormal growth and differentiation can result in foetal death, foetal abnormalities (anatomical defects, biochemical/functional defects, rare childhood syndromes)
• Progenitor cells


  Adult stem cells that can renew themselves through mitotic division without limit, produce "daughter" progenitor cells that replicate and proliferate to replenish tissues
• Progenitor cell cycle


  1. Quiescent adult stem cell

  2. Mitosis (max 50-70 times)

  3. Senescence, cell cycle arrest

  4. Maturation, differentiation
• Types of cells based on replication rate

  • Labile cells (rapid replication, 16-24h cycle)
  • Stable cells (quiescent, can re-enter cell cycle when stimulated)
  • Static cells (terminally differentiated, do not typically divide)
• Labile cells in constant cell cycle have increased risk of DNA mutations due to replication errors, environmental exposures
• Stable cells


  Quiescent progenitor cells that can be stimulated to re-enter cell cycle and replenish tissues
• Static cells


  Mature, highly differentiated "permanent" cells that are not typically replaced when lost or damaged
• Adaptive growth


  Cells can divide (mitosis) to increase cell number, be selectively deleted (apoptosis) to decrease cell number, get larger (hypertrophy) to increase tissue size, or 'shrink' (atrophy) to decrease tissue size
• Hypertrophy


  Increased cell size (volume)
• Hyperplasia


  Increased cell number due to replication and/or decreased cell loss by apoptosis
• Hypertrophy is the only adaptive option for increased functional demand in static, terminally differentiated cells that cannot easily increase cell number
• Cardiac hypertrophy in systemic hypertension is an adaptive response, but increased risk of cell death and heart failure if not accompanied by increased arteriole density
• Hyperplasia can be a normal adaptive response (e.g. enlargement of sex organs at puberty, breast tissue in pregnancy) or associated with disease (e.g. endometrial glandular hyperplasia)
• Atrophy


  Decreased size of an organ due to decreased cell size and/or cell number, results in diminished functional ability
• Atrophy can be reversible if due to decreased cell size or decreased cell number in labile or stable tissues, but irreversible in static tissues that cannot replace lost cells
• Increased number of glandular endometrial cells

  • Due to high levels of oestrogens, combined with insufficient levels of the progesterone-like hormones in conditions such as polycystic ovary syndrome
• Atrophy


  Decreased size of an organ
• Atrophy


  • Results in a decreased size of the organ
  • May be due to a decrease in cell size and/or cell number
  • Results in a diminished functional ability
  • Can be reversible if due to a decrease in cell size or if due to a decrease in cell number in a labile or stable tissue
  • Cell death in tissues with static ("permanent") cells results in irreversible cellular atrophy
• Causes of atrophy


  • Immobilisation (less functional requirement) leading to skeletal muscle atrophy
  • Starvation leading to atrophy of white adipose tissue
  • Atherosclerosis interfering with blood supply leading to skeletal muscle atrophy
  • Normal aspect of aging e.g. decrease in endometrial cellularity after menopause
• Hypoplasia


  Failure of a tissue to reach normal size during development due to decreased proliferation or mismatch between replacement and death of cells
• Hypoplasia is different from adaptive atrophy
• Metaplasia


  An acquired change in differentiation of a cell due to changes in environmental/cellular communication signals, resulting in a different cell type more suited to the environmental insult/stimulus
• Metaplasia


  • Altered differentiation (transformation)
  • An adaptive and reversible change
  • Involves changes in cellular communication
  • A protective mechanism against persistent cellular trauma
  • Reverses when the environmental "stress" is removed
• Types of metaplasia


  • Squamous metaplasia - change from columnar to squamous epithelium
  • Glandular metaplasia - change from squamous to glandular epithelium
• Squamous metaplasia of respiratory epithelium occurs in smokers, where the normal columnar respiratory epithelium changes to more resilient squamous epithelium
• Glandular metaplasia of the oesophagus occurs due to chronic gastro-oesophageal reflux disease (GERD), where the normal squamous epithelium transforms to a gastric-type epithelium
• Dysplasia


  Abnormal organisation of cells due to mutational changes in genes and abnormal differentiation, resulting in atypical cells with unusual shape and size
• Dysplasia


  • Increased replication rate of cells in response to cellular injury
  • Increased number of mitotic cells (labile cells) in the tissue
  • Aberrant cellular communication and atypical tissue architecture
  • Accumulation of abnormalities (mutations) in the somatic genome
• Mild/early forms of dysplasia may reverse if the chronic stimulus is removed, but severe dysplasia can progress to development of neoplasm
• Neoplasia


  Uncontrolled excessive autonomous growth and disordered (aberrant) differentiation and organisation of cells, resulting in a neoplasm that can only stop growing when there is no more oxygen and nutrients
• Dysplasia


  Pre-neoplastic condition, can progress to neoplasia with additional somatic mutations
• The key difference between dysplasia and neoplasia is that dysplastic cells are not autonomous and do not have an indefinite replicative ability, while neoplastic cells are immortal and have autonomous growth