L1 & L2 Intro to Pathology, Cell Injury and Death

• Pathology


  Medicine that describes dis-ease, the abnormal
• Pathology


  • Starts by understanding NORMAL anatomy, physiology, biochemistry, genetics, proteonomics, etc
  • Provides the link between basic biological science and clinical practice- bench to bedside

  
• Most commonly observed major discrepancies were myocardial infarction, pulmonary embolism and pneumonia
• Importance of autopsies


  • To diagnose new problems
  • Inform family members- COD and genetic problems
  • Confirm clinical diagnoses
  • Assist the Justice system
  • Ensure accurate health statistics
  • For health spending
  • Medical education
  • Quality assurance – still the 'gold standard' in diagnosis

  
• Specialty of Pathology


  • Anatomic Pathology- Histology, Cytology, Surgical Pathology
  • Microbiology, Virology
  • Clinical Biochemistry, Chemical Pathology
  • Immunology
  • Haematology, Blood Transfusion Services
  • Cytogenetics, Genetics, Molecular Pathology
• H&E (haematoxylin and eosin) stains dense connective tissue, with mature fibroblasts (F) embedded in collagen fibers
• Causes of cell injury

  • Hypoxia – oxygen deprivation
  • Chemical agents
  • Infectious agents
  • Physical agents
  • Immunologic reactions
  • Genetic
  • Nutritional imbalance
  • Diabetes, Atherosclerosis
  • Starvation/Deficiency
  • Excess
• Ischaemia


  Loss of blood supply to a tissue, due to impeded arterial supply
• Cardio-respiratory failure


  Inadequate oxygenation e.g. pneumonia
• Reduced oxygen carrying capacity of blood


  Severe anaemia, Carbon monoxide poisoning
• Cell injury


  • Cell function is lost before morphological signs of injury are apparent
  • Cell Stress
  • Adaptation
  • Injury (reversible, irreversible)
  • Death
• Morphological cell changes with reversible injury and adaptation


  • Reversible cell swelling and blebbing
  • Cell accumulations
• Steatosis


  Accumulation of triglycerides, most noticeable in liver
• Hyperplasia


  Increase in number of cells and hence organ size
• Hypertrophy


  Increase in cell size and, consequently, organ size
• Physiologic hypertrophy


  • Increased blood pressure- Hypertension
• Atrophy


  Decrease in cell size and organ size
• Metaplasia


  Reversible change in adult cell type
• Limit to hypertrophy


  • Continued demand leads to necrosis
• Physiologic hypertrophy of the uterus

  During pregnancy
• Normal thickness LV wall

  • 10-15mm
• Increased blood pressure


  Hypertension
• Unilateral renal atrophy


  Due to impaired blood supply
• Atrophy of cerebral cortex

  In Alzheimer's disease
• Reversible change in adult cell type

  1. Reprogramming of stem cells, present in epithelium or mesenchyme

  2. Cells sensitive to a particular stress can be replaced by a "tougher" type

  3. Epithelial metaplasia

  4. Replacement of pseudostratified ciliated columnar epithelium of respiratory tract by squamous epithelium in cigarette smokers

  5. While it may confer survival advantages to epithelium, important functions are often lost

  6. Mucus secretion, ciliary action

  7. If stimulus persists, the metaplastic epithelium may become dysplastic and even progress to malignancy

  8. Squamous cell carcinomas of cervix and lung
• Dysplasia


  Disordered cellular morphology, organisation and function, a pre-malignant change
• Adaptation versus injury
• Necrosis


  Cell homicide
• Apoptosis


  Cell suicide
• Types of apoptosis


  • Physiological apoptosis
  • Pathological apoptosis
• Cellular response depends on cell type, severity of injury, and ability to regenerate
• Necrosis


  • Pyknosis
  • Karyorrhexis
  • Karyolysis
• Distinct morphological patterns of necrosis

  • Coagulative necrosis
  • Liquefactive necrosis
  • Caseous necrosis
  • Gangrenous necrosis
• Coagulative necrosis


  • Myocardial infarction
• Gangrenous necrosis


  • Ischaemic coagulative necrosis of a limb or digit
• Liquefactive necrosis


  Transformation of necrotic tissue into a liquid viscous mass
• Liquefactive necrosis


  • Brain abscess
  • Healed brain infarct (stroke)
• Caseous necrosis


  Necrosis associated with chronic inflammation, observed in tuberculosis, appears white and cheesy
• Key terms


  • Cell injury/organ injury
  • Oedema, cellular accumulations
  • Proliferation/regeneration, hyperplasia, hypertrophy, atrophy, metaplasia, dysplasia
  • Disturbance of function and irreversible injury
  • Cell death/organ death/death, necrosis, pyknosis, karyorrhexis, karyolysis, apoptosis
  • Coagulative, liquefactive, caseous
  • Acute inflammation, chronic inflammation, healing
• Inflammation


  A protective response, intended to detect and eliminate the cause of cell injury, and then "clean up" after the injury