Obgy

• Hypoxia


  The most common cause of cell injury
• Ischemia


  The most common cause of Hypoxia
• Brain/neurons


  • The most sensitive cell to Hypoxia
• Fibroblast


  • The most resistant cell to Hypoxia
• Myelin Figures


  Also called Concentric Lamellation, composed primarily of phospholipids and minor calcium
• Cell injury


  1. Injury

  2. Adaptation fails

  3. Reversible cell injury

  4. Injury continues

  5. Irreversible (cell death) cell injury
• Reversible Cell Injury


  • Mitochondrial Dysfunction causes decrease in ATP production
  • Anaerobic Glycolysis causes acidic pH and nuclear chromatin clumping
  • Decrease in Protein Synthesis
  • Failure of Na K ATPase Pump causes H2O influx and Hydropic Change (cellular swelling, ER swelling, flattening of microvilli, cytoplasmic blebs)
  • Ribosome detachment leads to decreased protein synthesis
  • Associated with fatty change
• Irreversible Cell Injury

  • Severe Membrane Damage causes influx of calcium and activation of phospholipase, protease, and nuclease enzymes
  • Severe Mitochondrial Damage causes calcium deposition and Amorphous Flocculent Densities
• Pyknosis


  Nucleus becomes small and dark due to nuclear chromatin condensation
• Karyorrhexis


  Nuclear Fragmentation
• Karyolysis


  Nucleus gets dissolved
• Necrosis


  Pathological Cell Death associated with inflammation
• Ghost Cells


  Associated with Coagulative Necrosis, seen in skin-generated tumors like Pilomatrixoma
• Apoptosis


  Programmed cell death, both physiological and pathological, involving mitochondria and caspase-dependent pathways
• Mechanism of Apoptosis


  1. Initiation (Extrinsic Pathway via CD95/Fas and Intrinsic Mitochondrial Pathway)

  2. Execution (activation of caspase 3, 6, 7 leading to DNA fragmentation and formation of apoptotic bodies)
• Efferocytosis


  Phagocytosis of apoptotic bodies by macrophages, signaled by "eat me" markers like phosphatidylserine
• Cancer cells express CD47 as a "do not eat me" signal to avoid phagocytosis by macrophages
• Apoptosis can be identified by markers like Annexin V, CD95/Fas, nuclear chromatin condensation, TUNEL staining, and DNA laddering
• Necroptosis


  Caspase-independent programmed necrotic cell death, involved in processes like steatohepatitis, pancreatitis, and reperfusion injury
• Newer cell death pathways include necroptosis, pyroptosis, ferroptosis, and anoikis
• in which skeletal muscles?
• Rectus Abdominis


  A skeletal muscle
• Newer Cell Deaths
• Newer cell death types

  • Necroptosis
  • Pyroptosis
  • Ferroptosis
  • Anoikis
• Necroptosis


  Necrosis + Apoptosis
• Necroptosis


  Caspase independent programmed cell death
• Characteristics of Necrosis, Apoptosis, and Necroptosis

  • Necrosis: Morphology, Inflammation
  • Apoptosis: Programmed cell death
  • Necroptosis: Physiological (Growth Plate Formation in Human Body), Pathological (Steatohepatitis, Pancreatitis, Reperfusion Injury)
• Programmed Necrosis


  New term for Necroptosis
• CMV does not undergo apoptosis due to the presence of caspase inhibitors, it undergoes necroptosis (caspase independent)
• Mechanism of Necroptosis


  1. TNF binds to TNF receptor

  2. RIPK1, RIPK3, PROCASPASE 8 form a trio

  3. MLKL phosphorylation results in cell death
• Pyroptosis


  Pyro means Fever, tosis means cell death, associated with microorganisms
• Pyroptosis mechanism

  Bacteria enters body, binds to NOD receptors, activates inflammasomes, activates CASPASE 1, activates IL-1, causes fever, leads to cell death
• Anoikis

  Type of apoptosis that occurs when cells lack their natural environment
• Incorrect statement about Necroptosis: Caspase 8 is required
• Incorrect statement about Pyroptosis: TLR is used
• Cellular Adaptations


  • Hypertrophy
  • Hyperplasia
  • Atrophy
  • Metaplasia
• Dysplasia


  Precancerous condition
• Hypertrophy

  Increase in cell size, number remains same
• Hyperplasia


  Increase in cell number, size remains same
• Benign Prostatic Hyperplasia is now called Nodular Hyperplasia of the Prostate, caused by testosterone converting to DHT via 5 alpha reductase