细胞对于stress的反应

这是一篇关于细胞对于stress的反应的思维导图，主要内容有Cellular responses to stress、Causes of cell injury、Mechanisms of cell injury。

cellular adaptation

• Cellular responses to stress
  • Cells normally maintain a steady-state called homeostasis in which physiological parameters are kept
  • If cells encounter a physiological stress or pathological stimuli they can undergo adaptation, achieving a new steady state and preserving viability and function生存能力和功能
  • principal adaptive responses
    • hypertrophy肥大
      • Hypertrophy is an increase in the size of cells resulting in increase in the size of the organ
      • 细胞的数量不变，但细胞变大
      • can be 生理性的或病理性的 and can be caused either by
        • increased functional demands
        • growth factors or hormonal stimulation
    • hyperplasia增生
      • Hyperplasia is characterised by an increase in cell number because of proliferation of differentiated cells and replacement by tissue stem cells
      • can be physiological or pathological
        • 在两者情况下，cellular proliferation都是由很多类细胞所产生的生长因子所刺激
        • physiological hyperplasia:2
          • Hormonal hyperplasia
            • i.e. the proliferation of the glandular epithelium of the female breast during pregnancy
          • Compensatory hyperplasia
            • in which residual tissue grows after removal or loss of part of an organ (i.e. liver restoration after a surgery
        • pathological hyperplasia:
          • caused by excessive hormonal or growth factor stimulation
          • 所以增生过程需要被控制，如果触发增生过程的信号停止，增生消失
          • 增生对于正常的管控控制有反应，这能够区分病理性增生和cancer
          • 病理性激素增生例子Hyperplasia reversible with appropriate treatment
            • benign prostate hyperplasia
            • goiters甲状腺肿
              • endemic-dietary iodine deficiency or goitrogen ingestion
              • Graves's disease(autoimmune stimulation of TSH receptor by an IgG)
      • 总结:increased cell number in response to hormones and growth factors
    • atrophy萎缩
      • is the shrinkage of the size of cells by the loss of cell substance细胞数目不变，细胞大小减少
      • Atrophic cells have diminished functions, but they are not dead
      • 总结：Decreased cell and organ size, as a result of decreased nutrient supply or disease
    • metaplasia化生
      • is a reversible change in which one adult (differentiated) cell type is replaced by another adult cell type
      • squamous changes that occur in the lungs of cigarette smokers：columnar become squamous
      • 总结：Change in phenotype of differentiated cells in response to chronic irritation. May result in decreased function or increased propensity formalignant transformation
  • If the adaptive capability is exceeded or if the external stress is harmful, cell injury develops
    • reversible,cell may return to a stable baseline
    • irreversible,if stress is severe, persistent and rapid in onset
      • the affected cells will die
  • adaptation
    • Adaptations are reversible changes in the number, size, phenotype, metabolic activity or function of cells
      • Physiological adaptations:usuall 代表了细胞对于正常次级的反应，比如激素
      • pathological adaptation：是一种允许细胞去调整他们结构和功能因此逃避损伤的对于压力的反应
• Causes of cell injury
  • ischemia and hypoxia
  • physical agents(温度，pressure,electricity,radiation,trauma)
  • chemicals(drugs,poisons,venoms毒液）
  • microbes(病毒，细菌，真菌，protozoa,worms)
  • immunological reactions
  • genetical defects
  • nutrition(deficiency,imbalance)
  • ageing
• Mechanisms of cell injury
  • 细胞对于有害刺激的反应取决于types of injury,its duration and its severity
  • 对于有害刺激的结果取决于受损害细胞的类型，status adaptability,genetic makeup腿部肌肉细胞在完全缺血状态下可停留2-3小时，而心肌细胞在20-30分钟内死亡
  • 4 mechanisms
    • Mitochondria and their ability to generate ATP and ROS under pathological conditions
      • energy depletion(ATP)
        • 细胞膜ATP-dependent sodium pump的活性减少，anaerobic glycosis 补偿性增加，prolonged ATP depletion cause structural disruption of protein synthetic apparatus核糖体
      • mitochondrial permeability
        • 线粒体破坏，dysfunction:causes
          • depletion of ATP,导致细胞坏死
          • 导致ROS的形成
          • 线粒体通透性孔的形成，leading to pH and 膜电位的改变
          • 细胞凋亡
      • free radicals, reactive oxygen species(ROS)
        • Free radicals are chemical species with a single unpaired electron in an outer orbital • Such chemical states are extremely unstable and they may attack nucleic acids and cellular proteins and lipids • Reactive Oxygen Species (ROS) are a type of oxygen-derived free radicals that may induce cell injury
          • 在线粒体氧化还原反应中ROS在所有细胞中正常地被少量产生
          • ROS被phagocytic白细胞产生去毁灭摄入的微生物
        • effect of ROS
          • damage of ROS is determined by their rates of production and removal
            • Generation of ROS may be increased under several circumstances (UV-light, X-rays, inflammation)
            • Cells have developed mechanisms to remove free radicals and to minimise injury
    • Disturbance in calcium homeostasis
      • cytosolic calcium increase
        • Increased cytosolic Ca2+activates a number of enzymes with many cellular effects and may induce apoptosis
    • Damage to cellular membrane
      • membrane damage and permeability changes
        • Increased membrane permeability ultimately leads to necrosis Several biochemical mechanisms may contribute to membrane damage:
          • decreased phospholipid synthesis
          • increased phospholipid breakdown(and products)
          • ROS
          • cytoskeletal abnormalities
    • DNA damage and misfolding of proteins
      • DNA and protein structural damage
        • In particular conditions (i.e. UV light, Xrays…) DNA and proteins can get damaged
        • Structural damage of DNA and proteins will alter their function and will imbalance the pathways they regulate,这会导致细胞死亡
• ROS
• cell death 2
  • necrosis:Necrosis happens when damage to membranes is severe, enzymes leak out of lysosomes and digest the cell, the major pathway of cell death in many injuries (i.e. ischemia, infections and trauma)
  • apoptosis:Apoptosis happens in a cell damaged beyond repair which commits itself to “suicide”