cell injury

• Lecture 1: Cell injury, adaptations and cell death

  27.1.2021
• Cell injury

  A variety of stresses a cell encounters as a result of changes to its internal and external environment
• Types of cell injury

  • Reversible (sublethal damage)
  • Irreversible (lethal damage)
• Cell injury exists on a spectrum
• Aetiology of cell injury

  • hypoxia
  • ischemia
  • toxin-induced (e.g., ethanol and cigarette smoking)
  • infectious agents
  • genetic abnormalities
  • aging
  • imbalances in nutrition
  • physical causes (e.g. trauma)
• Mechanism of injury

  1. Extensive DNA damage and chromatin clumping, changes to nucleus (pyknosis, karyorrhexis and karyolysis)

  2. ATP levels are reduced leading to reduced Na+/K+ ATPase activity causing cellular and endoplasmic reticulum swelling, reduced calcium pump activity which alters calcium homeostasis (reduced activity of NCX pump)

  3. ↑ anaerobic glycolysis which subsequently leads to glycogen depletion and ↑ lactic acid

  4. Mitochondrial damage (caused by reactive oxygen species, increased intracellular calcium levels and hypoxia), can lead to increased mitochondrial permeability which causes reduced oxidative phosphorylation and leakage of apoptotic proteins, ↑ reactive oxygen species
• Pyknosis

  Nuclear shrinkage
• Karyorrhexis

  Nuclear fragmentation
• Karyolysis

  Nuclear fading
• Reversible injury

  • Decreased ATP levels
  • Amorphous densities in the mitochondria and increased mitochondria permeability
  • Ion imbalances (Na+ and Ca++)
  • Severe membrane damage in cell and organelle membranes
  • Cellular swelling
  • Lysosomal rupture and autolysis
  • Decreased pH due to anaerobic metabolism
• Irreversible injury

  • Extensive DNA damage and chromatin clumping
  • Ribosomal detachment
  • Changes to nucleus (pyknosis, karyorrhexis and karyolysis)
• Reversible and irreversible injury effects

  • Intracellular oedema (impaired Na+, K+ ion conc. at membrane)
  • Fatty change (accumulation of fat in non-fatty cells; steatosis of liver)
  • Amyloidosis (deposition of fibrillary protein substance called amyloid)
  • Pathological pigment accumulation (melanin, lipofuscin, haemosiderin)
• Cell death is a state of irreversible injury
• Changes that follow cell death

  • Gangrene
  • Pathologic calcification
• Cellular adaptations

  Reversible changes in size, number, phenotype, metabolic activity or function of cells in response to changes in their environment
• Cell must constantly adapt
• Types of cellular adaptations

  • Physiological change to stimulation by hormones or endogenous chemical substances
  • Pathological changes may share similar underlying mechanisms
• Metaplasia

  Reversible change in differentiation from one type of fully differentiated cell type to another, usually in response to chronic irritation
• Dysplasia

  Abnormal maturation of cells resulting in change in shape, size and organisation, this is premalignant but may however be reversible
• Epithelial metaplasia

  • Squamous metaplasia: changes in the bronchus due to smoke
  • Columnar metaplasia: intestinal metaplasia in Barrett's oesaphagus
• Mesenchymal metaplasia

  • Cartilaginous metaplasia
• Dysplasia

  • Dysplastic changes in the uterine cervix epithelial
• Metaplasia of columnar to squamous epithelium in the bronchus
• Hyperplasia

  Increase in the number of cells in a tissue or organs
• Hypertrophy

  Increase in tissue or organ size owing to increase in the size of cells, without the increase in the number of cells
• Atrophy

  Acquired loss of size due to reduction of cell size or number of parenchyma cells in an organ
• Hyperplasia

  • Hormonal: influence of hormonal stimulation- hyperplasia of the female breast epithelium at puberty or during pregnancy
  • Compensatory: Hyperplasia occurring following removal of an organ- regeneration of the liver following partial hepatectomy
  • Pathological: Excessive stimulation of hormones or growth factors- endometrial hyperplasia
• Hypertrophy

  • Physiological: hypertrophy and hyperplasia of the uterus during pregnancy
  • Pathological: hypertrophy of the left ventricle
• Atrophy

  • Atrophy of brain due to aging
  • Atrophy of gonads after menopause
  • Pathological atrophy: Starvation atrophy, Ischaemic atrophy
• Types of cell death

  • Programmed
  • Non-programmed
  • Programmed necrosis
  • Apoptosis
  • Necrosis
  • Necroptosis
  • Pyroptosis
  • Ferropotosis
  • Autophagy
• Cell death due to various injurious agents
• Necrosis

  The unprogrammed death of cells or tissue in a living organisms, it is a pathological process following cellular injury that incites an inflammatory reaction
• Necrosis is due to loss of plasma membrane integrity with rupture and leakage of cell contents into the surrounding tissue
• The dead cells are degraded either by their own lysosomal content or that of other cells
• Aetiology of Necrosis


  • Depletion of intracellular energy systems
  • Production of oxygen free radicals
  • Disintegration of the nucleus
  • Plasma membrane alterations, disruption or failure
  • Alteration in ionic transport mechanisms
• Types of necrosis


  • Coagulative necrosis
  • Liquefactive necrosis
  • Caseous necrosis (caseation)
• Coagulative necrosis

  The most common form of necrosis, where the dead tissue is initially swollen and firm, but later becomes soft as a result of digestion by macrophages
• Coagulative necrosis is usually caused by ischaemia in solid tissue (i.e. kidney)
• Coagulative necrosis takes hours to develop
• The lack of plasma membrane during necrosis allows the leakage of cardiac enzymes into the bloodstream, the levels of these enzymes (i.e. troponin T/I) in the blood aid the diagnosis of a MI