pathoma

• Homeostasis


  An organ is in balance with the physiologic stress placed on it
• Growth adaptation


  An increase, decrease, or change in stress on an organ can result in changes in organ size
• Hyperplasia


  • Increase in the number of cells in an organ
• Hypertrophy


  • Increase in the size of cells in an organ
• Hyperplasia and hypertrophy


  Generally occur together, except in permanent tissues which can only undergo hypertrophy
• Pathologic hyperplasia can progress to dysplasia and cancer, except for benign prostatic hyperplasia
• Atrophy


  • Decrease in organ size due to decrease in cell size and number
• Metaplasia


  Change in cell type in response to a change in stress on an organ
• Metaplasia


  • Barrett's esophagus
  • Keratomalacia
  • Myositis ossificans
• Dysplasia


  Disordered cellular growth, often a precursor to cancer
• Aplasia


  Failure of cell production during embryogenesis
• Hypoplasia


  Decrease in cell production during embryogenesis, resulting in a relatively small organ
• Cellular injury occurs when a stress exceeds the cell's ability to adapt
• Hypoxia


  Low oxygen delivery to tissue, an important cause of cellular injury
• Causes of hypoxia


  • Ischemia
  • Hypoxemia
  • Decreased O2-carrying capacity of blood
• Ischemia


  Decreased blood flow through an organ
• Causes of ischemia


  • Decreased arterial perfusion
  • Decreased venous drainage
  • Shock
• Hypoxemia


  Low partial pressure of oxygen in the blood
• Causes of hypoxemia


  • High altitude
  • Hypoventilation
  • Diffusion defect
• Hypoxia


  Low oxygen delivery to tissue; important cause of cellular injury
• Oxidative phosphorylation


  1. Oxygen is the final electron acceptor

  2. Decreased oxygen impairs oxidative phosphorylation

  3. Decreased ATP production

  4. Lack of ATP leads to cellular injury
• Causes of hypoxia


  • Ischemia
  • Hypoxemia
  • Decreased O2-carrying capacity of blood
• Causes of ischemia


  • Decreased arterial perfusion (e.g. atherosclerosis)
  • Decreased venous drainage (e.g. Budd-Chiari syndrome)
  • Shock-generalized hypotension resulting in poor tissue perfusion
• Hypoxemia


  Low partial pressure of oxygen in the blood (PaO2 < 60 mm Hg, SaO2 < 90%)
• Causes of hypoxemia


  • High altitude-Decreased barometric pressure results in decreased PAO2
  • Hypoventilation-Increased PaCO2 results in decreased PAO2
  • Diffusion defect-PAO2 not able to push as much O2 into the blood due to a thicker diffusion barrier (e.g. interstitial pulmonary fibrosis)
  • V/Q mismatch-Blood bypasses oxygenated lung (circulation problem, e.g. right-to-left shunt), or oxygenated air cannot reach blood (ventilation problem, e.g. atelectasis)
• Decreased O2-carrying capacity


  Arises with hemoglobin (Hb) loss or dysfunction
• Examples of decreased O2-carrying capacity


  • Anemia (decrease in RBC mass)-PaO2 normal; SaO2 normal
  • Carbon monoxide poisoning-CO binds hemoglobin more avidly than oxygen, PaO2 normal; SaO2 decreased
  • Methemoglobinemia-Iron in heme is oxidized to Fe3+, which cannot bind oxygen, PaO2 normal; SaO2 decreased
• Reversible cellular injury


  Hallmark is cellular swelling
• Reversible injury


  • Cytosol swelling results in loss of microvilli and membrane blebbing
  • Swelling of the rough endoplasmic reticulum (RER) results in dissociation of ribosomes and decreased protein synthesis
• Irreversible cellular injury


  Hallmark is membrane damage
• Irreversible injury


  • Plasma membrane damage results in cytosolic enzymes leaking into the serum and additional calcium entering the cell
  • Mitochondrial membrane damage results in loss of the electron transport chain and cytochrome c leaking into cytosol (activates apoptosis)
  • Lysosome membrane damage results in hydrolytic enzymes leaking into the cytosol, which are activated by the high intracellular calcium
• The end result of irreversible injury is cell death
• Necrosis


  Death of large groups of cells followed by acute inflammation
• Necrosis is never physiologic, it is due to some underlying pathologic process</b>
• Types of necrosis based on gross features


  • Coagulative necrosis
  • Liquefactive necrosis
  • Gangrenous necrosis
  • Caseous necrosis
  • Fat necrosis
  • Fibrinoid necrosis
• Coagulative necrosis


  Necrotic tissue that remains firm, cell shape and organ structure are preserved by coagulation of proteins, but the nucleus disappears
• Liquefactive necrosis


  Necrotic tissue that becomes liquefied, enzymatic lysis of cells and protein results in liquefaction
• Gangrenous necrosis


  Coagulative necrosis that resembles mummified tissue (dry gangrene)
• Caseous necrosis


  Soft and friable necrotic tissue with "cottage cheese-like" appearance, combination of coagulative and liquefactive necrosis
• Fat necrosis


  Necrotic adipose tissue with chalky-white appearance due to deposition of calcium