Module 4

• Adaptive changes


  Cells' responses to stress in an attempt to maintain homeostasis
• Types of adaptive changes

  • Hypertrophy: Increase in cell size
  • Hyperplasia: Increase in cell number
  • Atrophy: Degeneration of cells
  • Metaplasia: Change in cell type
  • Dysplasia: Change in cell abnormally
• Reversible injury


  Cells' more extreme response to continued cellular stress causing injury that without proper intervention will lead to severe pathologies that can cause death
• Reversible injury


  • Generalized cell swelling, plasma blebbing, clumping of nuclear chromatin, decreased ATP generation, loss of cell membrane integrity, defects in protein synthesis, cytoskeleton damage, and DNA damage

  
• Irreversible injury


  Cells' most extreme response to cellular stress over time with no choice but cellular death (apoptosis[controlled]; necrosis[uncontrolled])
• Irreversible injury


  • Severe ER and mitochondrial swelling, lysosome rupture, blebbing progresses to membrane fragmentation, as well as nuclear membrane rupture and chromatin fragmentation
• Factors determining cell response to stress/injury

  • Labile- continuously replicating cells
  • Stable- cells capable of division in response to demand (stress)
  • Permanent- non-dividing cells

  
• Common examples of cellular adaptations


  • Connective tissue in the brain from cell death
  • Increase in organ size due to hyperplasia
• Psychological adaptation


  Increase in workload either mechanically or metabolically, or due to hormonal stimulation
• Pathological adaptation


  Increase in resistance or abnormal increase in hormonal stimulation, could be caused due to a physical obstruction or may be genetically determined
• Possible causes of cell injury

  • Reactive oxygen and nitrogen species
  • Neoplasia causing increased hormone production and action
  • Physical obstruction or decrease in flow of nutrients
• Hydropic change


  Acute swelling due to a failure in energy dependent ion pumps within the membrane thus causing a disturbance in ion and fluid homeostasis leading to water overload
• Hydropic change


  • Macroscopic: enlarged and pale organs (rare to see unless extreme)
  • Microscopic: cytoplasm will be pale and clear, cloudy swelling
• Fatty change


  Increase lipids within the cells leading to hypoxic, or toxic/metabolic injury
• Fatty change


  • Macroscopic: enlarged and pale organs, soft and greasy
  • Microscopic: macrovesicular and microvesicular patterns
• Glycogen overload


  Buildup of glycogen similar to fatty change
• Chromatolysis


  Neurons' internal degeneration of special bodies called nissl bodies within their cell body and dispersed within the cell
• Common causes of reversible injury in domestic species


  • Reactive oxygen species
  • Physical agents
  • Chemicals
  • Drugs
  • Toxins
  • Infectious agents
  • Immunological dysfunction
  • Genetic defects
  • Nutritional deficiencies and imbalance
• Progression of reversible to irreversible cell injury

  1. Pyknosis

  2. Karyorrhexis

  3. Karyolysis

  4. Absence

  
• Oxidative stress


  Damage caused by free radicals (molecules with an unpaired electron) like ROS or RNS (and your antioxidant lvls are too low to fight of the higher lvls of free radicals)
• Hypoxia


  State at which oxygen is not available in sufficient amounts at the tissue level to maintain adequate homeostasis
• Ischaemia


  Condition in which blood flow (and thus oxygen) is restricted or reduced within a part of the body
• Infarction


  Death of tissue resulting from a failure of blood supply, commonly due to obstruction of a blood vessel by a blood clot or narrowing of the blood-vessel channel
• Apoptosis (physiological)


  Programmed cell death that allows the surrounding cells and the organ as a whole to continue to function and maintain homeostasis
• Apoptosis (pathological)

  Cell death caused by some type of disease
• Necrosis is less controlled than apoptosis
• Common intracellular/extracellular accumulations

  • Cytochrome C
  • Apoptotic proteins
  • BCL2 receptors
  • Receptor ligand interactions on the cell surface
• Amyloidosis (secondary)


  From chronic inflammation or neoplasia (over production of normal proteins)
• Amyloidosis (primary)

  From plasma cell tumours
• Dystrophic calcification

  Calcium build up associated with necrosis (coagulative, caseous, and fat) the dying cells can not regulate their cytoplasmic calcium leading to a build up of calcium in the mitochondria
• Metastatic calcification


  Calcium build up occurs in normal cells, secondary to hypercalcemia; large amounts of calcium enter the cell and build up on the organelles, primarily the mitochondria
• Gout

  Build up of crystals formed from uric acid, primarily an issue in reptiles, birds, and humans since they lack uricase. Commonly caused by a vit A deficiency, high protein diet, and/or renal injury.
• Necrosis

  Cell size increases, nucleus degrades from pyknosis to karyorrhexis to karyolysis, cell membrane is disrupted and the cell begins digesting itself from destroyed lysozyme enzyme leaking out
• Types of necrosis

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

  • Cellular outlines/basic tissues architecture is preserved temporarily; ischemia or toxin induced

  
• Liquefactive necrosis


  • Necrosis of cells in the CNS cavity filled with liquefactive necrotic material (pus)
• Caseous necrosis

  • Friable, "cheese like"; component cells dead and architecture lost
• Gangrenous necrosis

  • 3 types: Moist, Dry, Gas; necrosis with an infection
• Fat necrosis


  • Specific necrosis of fat
• Absorption


  Spread from the stomach and intestines into the bloodstream as the body takes in and digests the drug