Week 1: Altered Cellular and Tissue Biology

• Atrophy


  1. Cells shrink and reduce their differentiated functions in response to normal and injurious factors

  2. General causes: Disuse

  3. Denervation

  4. Ischemia

  5. Nutrient starvation

  6. Interruption of endocrine signals

  7. Persistent cell injury
• Hypertrophy


  1. Increase in cell mass accompanied by an augmented functional capacity in response to physiologic and pathophysiologic demands

  2. General cause: increased cellular protein content
• Hyperplasia


  1. Increase in functional capacity related to an increase in cell number due to mitotic division

  2. Usually in response to increased physiologic demands or hormonal stimulation

  3. Other causes: persistent cell injury, chronic irritation of epithelial cells

  4. Hyperplasia can lead to cancer: Example increased endometrial tissue with unopposed estrogen can lead to atypical hyperplasia then to endometrial cancer

  5. Callus formation
• Metaplasia


  1. Replacement of one differentiated cell type with another

  2. Common cause: adaptation to persistent injury, with replacement of a cell type that is better suited to tolerate injurious stimulation

  3. Fully reversible when injurious stimulation is removed

  4. Example is conversion of ciliated columnar epithelium to stratified squamous epithelium in response to chronic irritation of the bronchial mucosa by cigarette smoke- usually not cancerous
• Dysplasia


  1. Disorganized appearance of cells because of abnormal variations in size, shape, and arrangement

  2. Represents an adaptive effort gone astray

  3. Significant potential to transform into cancerous cells (preneoplastic lesions)

  4. Dysplasia that is seen on a biopsy of the cervix is called cervical intraepithelial neoplasia (CIN). It is grouped into three categories: CIN I -- mild dysplasia

  5. CIN II -- moderate to marked dysplasia

  6. CIN III -- severe dysplasia to carcinoma in situ
• Etiology of Cell Injury


  • Ischemia –lack of blood flow
  • Hypoxia –lack of oxygen
  • Nutrition deficits
  • Infection
  • Immune responses
  • Chemical
  • Physical and mechanical
• Ischemia


  An inadequate blood supply to an organ or part of the body
• Hypoxemia


  • Reduced oxygenation of arterial blood
  • Measured by ABG or pulse oximetry (O2 saturation)
• Hypoxia


  • Reduced oxygenation of cells in tissues
  • Difficult to measure (assume when blood flow or PaO2 is low)
  • Can be hypoxemia, low cardiac output, or a number of other variables
  • Pulse oximeter measures saturation of O2 in the blood. Normal oximetry readings are 95-100%. Below 90% is considered low.
• Ischemia causes more damage because

  Lack of nutrition and waste removal
• Tissue hypoxia is most often caused by ischemia


  Causes power failure in the cell
• Ischemic and Hypoxic Injury


  1. ↓O2 to mitochondria cause ATP production to stall and energy-dependent pumps to fails

  2. Na+ accumulation in cell results in swelling through osmosis

  3. Excess intracellular Ca2+ collects in mitochondria causing further dysfunction

  4. Anaerobic glycolysis produces some ATP but leads to pyruvate end products converted to lactate

  5. Lactate escapes in to bloodstream resulting in lactic acidosis

  6. Cellular proteins and enzymes become progressively more dysfunctional as the pH falls

  7. Cell death happens when the plasma, mitochondria and lysosome membranes are critically damaged.
• Ischemia-Reperfusion Injury


  • Exacerbation of cellular dysfunction and death following restoration of blood flow to previously ischemic tissues
  • A multi-factorial process resulting in extensive tissue destruction
  • Occurs in a wide range of organs including the heart, lung, kidney, gut, skeletal muscle and brain and may involve not only the ischemic organ but may also induce systemic damage to distant organs, potentially leading to multi-system organ failure.
• Ischemia-Reperfusion Injury


  1. Calcium overload inside cell

  2. Can trigger apoptosis or activate enzymes that degrade lipids

  3. Formation of free radicals

  4. Reactive oxygen molecules* (free radicals) generated that damage cell membranes, denature proteins and disrupt cell chromosomes

  5. Initiate the inflammation

  6. *superoxide (O2-); peroxide (H2O2); hydroxyl radicals (OH-)
• Ischemia-reperfusion Injury


  • Subsequent inflammation
  • WBCs recruited to the area release enzymes and other chemicals that further damage cells
• Necrosis


  • Usually occurs as a consequence of ischemia or toxic injury
  • Cell rupture, spilling of contents into extracellular fluid, and inflammation
• Apoptosis


  • Occurs in response to injury that does not directly kill the cell
  • Triggers intracellular cascades
  • Activates a cellular suicide response
  • Not always a pathologic process
  • Does not cause inflammation