T1: INTRO TO PATHO

• Pathology

  The study (logos) of disease (pathos, suffering)
• Etiology


  The origin of a disease, including the underlying causes and modifying factors
• Pathogenesis


  The steps in the development of disease. It describes how etiologic factors trigger cellular and molecular changes that give rise to the specific functional and structural abnormalities that characterize the disease
• Herophilus and Erasistratus provided a beginning for anatomical pathology and autopsy by performing the first scientific human cadaveric dissections over a period of 30 to 40 years
• Cell theory of disease by Virchow: A central premise is that disease starts from a cell as a result of its structural impairment
• Cells


  • Normally maintain a steady state called homeostasis in which the intracellular milieu is kept within a fairly narrow range of physiologic parameters
  • Can undergo adaptation, achieving a new steady state and preserving viability and function as they encounter physiologic stresses or pathologic stimuli
• Causes of cell stress or injury

  • Chemical agents
  • Immunologic reactions
  • Oxygen deprivation
  • Infectious agents
  • Genetic factors
  • Nutritional imbalances
  • Aging
  • Physical agents
• Ischemia


  Diminished blood flow to a tissue, a common cause of acute cell injury

  
• Hypoxia


  Reduced oxygen supply, in which energy generation by anaerobic glycolysis can continue (albeit less efficiently than by oxidative pathways)
• Ischemia-reperfusion injury: Restoration of blood flow to ischemic but viable tissues can result in the death of cells that are not otherwise irreversibly injured

  
• Chemical (toxic) injury


  Chemicals can act directly by combining with a critical molecular component or cellular organelle, or be converted to reactive toxic metabolites which then act on target cells
• Mechanisms of cell injury

  • Mitochondrial damage
  • Influx of calcium
  • Accumulation of reactive oxygen species
  • ATP depletion
  • Accumulation of damaged DNA and proteins
  • Increased permeability of cellular membranes
• ATP depletion


  Reduced supply of oxygen and nutrients, mitochondrial damage, and the actions of some toxins can cause ATP depletion, which is required for virtually all synthetic and degradative processes within the cell
• Influx of calcium


  Ischemia and certain toxins can cause an increase in cytosolic calcium concentration, which activates enzymes with potentially deleterious cellular effects
• Mitochondrial damage and dysfunction


  • Can result in failure/abnormal oxidative phosphorylation, high conductance formation in mitochondrial pore, and mitochondria signalling distress proteins
• Oxidative stress


  Free radicals are extremely unstable chemical species that avidly attack nucleic acids, cellular proteins and lipids
• Membrane permeability defects


  Increased membrane permeability leading to overt membrane damage is a consistent feature of most forms of cell injury that culminate in necrosis
• Damaged DNA and misfolded proteins can accumulate in cells under some circumstances
• Cell pigments

  • Carbon
  • Lipofuscin
  • Melanin
  • Hemosiderin
• Carbon


  A common exogenous pigment that is inhaled and phagocytosed by alveolar macrophages, blackening the draining lymph nodes and pulmonary parenchyma (anthracosis)
• Lipofuscin


  An insoluble brownish-yellow granular intercellular material that accumulates in tissues as a function of age or atrophy, a marker of past free radical injury
• Melanin


  An endogenous, brown-black pigment synthesized by melanocytes that acts as a screen against harmful ultraviolet radiation
• Hemosiderin


  A hemoglobin-derived granular pigment that accumulates in tissues when there is a local or systemic excess of iron
• Cellular adaptation to stress can involve changes in size, number and characteristics of cells
• Situs inversus is a rare genetic condition in which the organs in the chest and abdomen are reversed, usually harmless
• Types of necrosis

  • Coagulative necrosis
  • Colliquative necrosis
  • Caseous necrosis
  • Fat necrosis
• Primary changes in somatic death

  • Circulatory failure
  • Respiratory failure
  • CNS failure

  
• Secondary changes in somatic death

  • Algor mortis
  • Rigor mortis
  • Livor mortis
  • Postmortem clotting
  • Desiccation
  • Putrefaction
  • Autolysis
• Inflammation is the universal response to tissue injury
• White blood cells play a key role in inflammation
• Inflammation can be acute or chronic