1. Adaptation
    1. Atrophy
      1. ↓cellular size
      2. Physiologic atrophy
        1. e.g. Thymusgland
      3. Pathologic atrophy
        1. ↓workload, pressure, blood supply, nutrition, hormonal stimulation and nervous stimulation
        2. Immobilization- disuse atrophy
        3. Aging- brain cells and endocrine- dependent
      4. cellular properties
        1. Less endoplasmic reticulum
        2. Fewer mitochondria and myofilaments
        3. Decrease protein synthesis
        4. Increase protein catabolism
          1. Pathway
          2. Ubiquitin- proteosme pathway
          3. protein are first conjugated to ubiquitin Degrade within a large cytoplasmic proteolytic complex or proteosome
          4. Metabolic acidosis
          5. Glucocorticoids
          6. Thyroid hormone
          7. Chronic malnutrition
          8. Autophagic vacuoles
          9. Membrane
          10. Destroyed by lysosomes
          11. Lipofuscin
    2. Hypertrophy
      1. ↑cellular size & organ size by ↑protein in the cellular components
        1. Physiologic hypertrophy
          1. ↑workload
        2. Compensatory hypertrophy
          1. e.g. kidney
        3. Pathologic hypertrophy
          1. e.g. hypertension
    3. Hyperplasia
      1. mitotic division occur ↑ number of cell by:
        1. Increased workload
        2. Hormonal stimulation
        3. Decrease tissue density
      2. Physiologic
        1. e.g. endometrium
        2. Breast and uterine...pregnancy
      3. Compensatory
        1. regeneration of the liver after partial hepatectomy
      4. Pathologic
        1. Excessive hormone stimulation
    4. Metaplasia
      1. Reversible change of one cell type with another cell type
      2. Reprogramming of undifferentiated stem cells
      3. Causes
        1. Chronic irritation
        2. inflammation
      4. Physiologic
        1. e.g. monocytes trans. into macrophage
      5. Pathologic
        1. Extrinsic toxin or stressor, generally irreversible
        2. Exposure to cigerette smoke
    5. Dysplasia
      1. Abnormal differentiation of dividing cells
      2. abnormal in size, shape and appearance
      3. Potentially reversible
      4. may be a precursor of cancer
  2. Injury
    1. Hypoxic injury
      1. Result from
        1. ↓oxygen in the air
        2. ↓hemoglobin
        3. ↓production of RBC
        4. diseases of the resp. and CV systems
        5. poisoning of the oxidative enzymes
        6. ischemia
          1. arteriosclerosis
          2. thrombosis, embolus (cause anoxia)
      2. mechanisms
        1. ↓mitochondrial phophorylation
        2. ↓ATP production
        3. ↑ anaerobic metabolism - ↑ ATP from glycogen
        4. ↓Glycogen ↓anaerobic metabolism
        5. ↓ATP- failure of Na- K pump
        6. Sodium- calcium exchange fail
        7. Intracellular accumulation of sodium and calcium
        8. Diffusion of potassium out of the cell
        9. Sodium and water enter the cell freely
        10. Cellular swelling
        11. Cells bathe in the fluid rich in the calcium ions
        12. Cell membrane damage- rapid movement of calcium intracellularly
        13. Early dilation of the endoplasmic reticulum
        14. Ribosomes detach and reduce protein synthesis
      3. Cellular response
        1. Reversible if oxygen is restored
        2. If not, vacuolation within the cytoplasm, swelling of the lysosomes, mitochondrial swollen and membrane damage
        3. Accumulation of calcium- activates multiple enzyme systems
        4. Resulting in cytoskeleton disruption, membrane damage, activation of inflammation, DNA degradation and eventual cell death
        5. Irreversible damage
      4. Reperfusion
        1. Xanthine dehydrogenase→ xanthine oxidase
        2. superoxide and hydrogen peroxide
          1. membrane damage and mitochondria calcium overload
    2. Free radical injury
      1. sources
        1. Byproduct of many normal cellular reactions
          1. Energy generation
          2. Breakdown of lipids and proteins
          3. killing microbes by phagocytic white blood cell
        2. Molecular oxygen (O2)
          1. In mitochondria,+4e- toproduce duce water
          2. partially reduced intermediate species
          3. O2-, H2O2, OH.
        3. Transition metals
        4. Nitric oxide NO
      2. Initiated by
        1. Absorption of extreme energy sources
        2. Endogenous
        3. Enzymatics metabolic of exogenous chemical or drugs
      3. Reactions
        1. Lipid peroxidation x1
        2. Alterations of protein x2
        3. Alteration of DNA x6
      4. major antooxidant enzymes
        1. SOD
        2. Catalase
        3. Glutathione peroxidase
      5. Antioxidants
    3. Impaired calcium homeostasis
      1. Calcium/magnesium- ATPase exchange systems keep low intracellular calcium level
      2. Increase influx of Ca++ across the membrane and release from mitochrondria and E.R. when ischemia and presence of toxin
      3. Activates enzymes to damage cell membrane and cytoskeleton
    4. cellular injury
      1. Intentional and unintentional injuries
        1. Contusion
        2. Hematoma
        3. Blunt force injury
          1. Abrasion
          2. Laceration
          3. Fractures
        4. Sharp force injuries
        5. Gunshot wounds
          1. Entrance wounds
          2. Exit wounds
        6. Asphyxial injury- deprivation of oxygen
          1. Suffocation
          2. Strangulation
          3. Chemical asphyxiants
          4. Drowning
      2. Injury from physical agents
        1. Temperature extremes
          1. Hypothermic injury
          2. Hyperthermic injury
        2. Changes in atmospheric pressure
          1. Blast injury
          2. Decompression sickness or caisson disease
        3. Ionizing radiation
          1. X-rays, gamma rays, alpha and beta particles
        4. Illumination
          1. Flourescent lamps
          2. Eyestrain, obscured vision, and cataract formation
          3. Caused by light modulation
        5. Mechanical stresses
          1. Physical impact or irritation
        6. Noise
          1. Acoustic trauma and noise-induced hearing loss
      3. Chemical injury
        1. Lead
        2. Carbon monoxide
        3. Ethanol
          1. Acute alcoholism
          2. Acetaldehyde
          3. Fetal alcohol syndrome
        4. Mercury
        5. Social or street drugs-
      4. Injury from biologic agents
        1. Pathogenicity of a microorganism
        2. Virulence of a microorganism
        3. Disease-producing potential
          1. Invasion and destruction
          2. Toxin production
          3. Production of hypersensitivity reactions
        4. Immunologic and Inflammatory Injury
        5. Injurious Genetic Factors
      5. Injury from nutritional imbalances
        1. Essential nutrients are required for cells to function normally
        2. Deficient intake
        3. Excessive intake
  3. Neoplasia
  4. Aging
  5. death
    1. Necrosis
      1. Sum of cellular changes after local cell death and the process of cellular autodigestion
      2. Processes
        1. Clumping of the nucleus
        2. Karyolysis
        3. Karyorrhexis
      3. Coagulative necrosis
        1. Kidneys, heart, and adrenal glands
        2. Due to hypoxia
        3. Protein denaturation
          1. Gelatine transparent → firm, opaque
          2. Abnormality in intracellular level of Ca++
      4. Liquefactive necrosis
        1. Neurons and glial cells of the brain
        2. Soft, liquefies
        3. Causes: ischemic or bacterial
      5. Caseous necrosis
        1. Tuberculous pulmonary infection
        2. coagulative+liquefactive necrosis
      6. Fat necrosis
        1. Action of lipases
        2. Opaque and chalk white
      7. Gangrenous
        1. arteriosclerosis/ blockage of major arteries, esp. in lower leg
    2. Somatic Death
      1. Death of an entire person
      2. Postmortem changes