HISOPATH

• Etiology

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


  The steps in the development of disease, describing how etiologic factors trigger cellular and molecular changes that give rise to the specific functional and structural abnormalities that characterize the disease
• Stages of disease process


  • Stage of Susceptibility
  • Stage of Subclinical Disease
  • Stage of Clinical Disease
  • Stage of Recovery, Disability or Death

  
• Stage of Susceptibility


  Individuals are exposed to risk factors, the time of exposure
• Stage of Subclinical Disease


  Pathologic changes present but no signs and symptoms, or non-specific signs and symptoms

  
• Stage of Clinical Disease


  Observable signs and symptoms, time of diagnosis as signs and symptoms are specific

  
• Branches of pathology


  • Anatomical pathology
  • Clinical pathology
  • Molecular pathology
  • Forensic pathology
• Anatomical pathology


  Talks about cells and tissues
• Clinical pathology


  Also called "Laboratory Medicine", includes chemistry, hematology, microbiology, transfusion services
• Molecular pathology


  Includes cytogenetics and molecular diagnostics
• Forensic pathology


  Includes autopsy and forensic toxicology
• 10 steps in tissue processing


  • Fixation
  • Dehydration/Decalcification
  • Clearing
  • Infiltration
  • Embedding
  • Trimming
  • Microtomy
  • Staining
  • Mounting
  • Labeling
• Decalcification is only an additional step necessary for processing calcified tissues like bones and calcified cartilage
• Herophilus and Erasistratus


  Greek physicians considered the fathers of anatomical pathology and autopsy, performed the first scientific human cadaveric dissections
• Pathology


  From the Greek words "pathos" meaning disease/suffering and "logos" meaning study
• Histopathology


  The study of the disease of tissues, from the Greek words "histo" meaning tissue, "pathos" meaning disease/suffering, and "logos" meaning study
• If an organ, organ system or organism is affected, it could lead to the rise of signs and symptoms
• Cell theory timeline


  • Zacharias Janssen invented the first compound microscope in 1590
  • Robert Hooke used a light microscope to look at thin slices of plant tissue (cork) and coined the term "cell" in 1665
  • Anton Van Leeuwenhoek first saw living organisms under a microscope and termed them "animalcules" in 1673
  • Matthias Schleiden stated that all living plants are made of cells and developed the first two tenets of the cell theory in 1838
  • Theodore Schwann stated that all living animals are made of cells and developed the first two tenets of the cell theory in 1839
  • Rudolf Virchow stated that where a cell exists, there must have been a pre-existing cell, developing the third tenet of the cell theory
• Virchow's cell theory of disease


  The central premise is that disease starts from a cell as a result of its structural impairment
• Homeostasis


  Maintaining the stability or internal stability of our body
• Hemostasis


  The stopping or control of bleeding in response to an avascular injury
• Causes of cell stress or injury


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


  Lack of oxygen availability in tissues
• Hypoxemia


  Decrease in oxygen in the blood, arterial PO2 less than 80mmHg
• Dysoxia


  Lack of oxygen utilization by tissues, there is available oxygen but it is not well utilized
• Ischemia


  Decreased blood flow, a reversible process leading to hypoxia and angina/chest pain
• Infarction


  Complete cut-off of blood flow, an irreversible process leading to necrosis
• Ischemia can progress into infarction


  If the underlying cause is not corrected or treated
• Ischemia


  A common cause of acute cell injury, restricts delivery of oxygen and nutrients/substrates, leads to no aerobic metabolism and no anaerobic glycolysis
• Hypoxia


  Energy generation of anaerobic glycolysis can continue, but blood flow is oxygen deficient, leading to no aerobic metabolism
• Ischemia-reperfusion injury


  Restoration of blood flow to ischemic but viable tissues results in the death of cells that are not otherwise irreversibly injured, mainly caused by dysfunctional ion transport mechanisms and increased reactive oxygen species
• Causes of cell injury: chemical (toxic) injury


  • Direct toxicity - chemicals that directly damage cells
  • Metabolic toxicity - induced through toxic metabolites
• Mechanisms of cell injury


  • ATP depletion
  • Influx of calcium activating degradative enzymes
  • Mitochondrial damage decreasing ATP and increasing reactive oxygen species
  • Accumulation of reactive oxygen species
  • Accumulation of damaged DNA and proteins
  • Increased permeability of cellular membranes
• Cell pigments


  • Carbon - black
  • Lipofuscin - brownish-yellow "wear and tear pigment"
  • Melanin - brown-black
  • Hemosiderin - golden yellow-brown derived from hemoglobin
• Exogenous pigments


  Generated outside the body, e.g. carbon
• Endogenous pigments


  Generated inside the body, e.g. lipofuscin, melanin, hemosiderin
• Reversible vs irreversible cell injury

  • Reversible - cellular swelling, responses within homeostasis, cell returns to original state
  • Irreversible - heavy doses of toxins, anoxia, severe/prolonged hypoxia, unable to recover, leads to cell death (necrosis or apoptosis)
• Cellular adaptations to stress


  • Atrophy - decrease in number and size of cells
  • Hypertrophy - increase in size of cells
  • Hyperplasia - increase in number of cells
  • Metaplasia - transformation of one cell type into another
  • Dysplasia - abnormal development of cells
• Metaplasia


  One type of mature cell changing into another type, can occur in both epithelial and mesenchymal cells
• Dysplasia


  Change in phenotype (observable characteristics) of cells, pre-cancerous/disordered growth, can only occur in epithelial cells