Week 2

• Cellular Adaptation and Response to Injury involves understanding the normal physiology of a cell, the types of injurious stimuli it can face, and the various ways it can adapt and respond to injury.
• Normal Cell Physiology includes understanding the various stressors that a cell can face, such as physiological stress, and how it can adapt and survive.
• Injurious Stimuli can be physical, chemical, or infectious agents, and understanding their effects on a cell is crucial in understanding Cellular Adaptation and Response to Injury.
• Cell Injury can be caused by various factors, including nutritional imbalances, genetic defects, and intrinsic mechanisms such as sickle cell anaemia.
• Reversible and Irreversible Injury are different types of cell injury, each with its own set of targets and effects.
• Mitochondria are important in Cellular Adaptation and Response to Injury as they are the site of aerobic respiration, which leads to the production of ATP, a fundamental energy-carrying molecule in all living cells.
• Increased cytosolic calcium can cause various effects on a cell, including changes in gene expression and the activation of stress response pathways.
• Reactive Oxygen Species (ROS) can cause cell injury through various mechanisms, including oxidative stress and free radical-induced damage.
• Ischaemic and hypoxic damage are types of cell injury that can occur due to reduced oxygen carrying capacity of blood, such as in cases of anaemia or CO poisoning.
• Chemical injury can be caused by a long list of drugs and poisons, including arsenic and acids/alkaline.
• Infectious agents and immunological reactions can cause cell injury, as can autoimmune diseases and genetic defects.
• Nutritional imbalances can cause cell injury, as can physical agents such as mechanical trauma, extremes of temperature, and chemical agents and drugs.
• Cell Injury can cause various effects on a cell, including decreased organ function, abnormal organ function, and changes in morphology.
• Normal Morphology can be affected by cell injury, with changes including karyorrhexis, karyolysis, and nuclear changes.
• Decreased organ function can be mechanical, synthetic, or detoxification, and can lead to effects such as heart failure, synthetic liver failure, and liver detoxification failure.
• Abnormal organ function can include epilepsy, cardiac arrhythmias, and the initiation of a reaction to injury.
• Cell Injury can lead to changes in organ function, including decreased organ function and abnormal organ function.
• Cellular Adaptation and Response to Injury includes normal cell physiological stress, cell death, and embryogenesis.
• Examples of physiological apoptosis are Embryogenesis via tissue morphogenesis, Hormone-dependent involution through endometrium in the menstrual cycle, Cell deletion in proliferating populations as seen in intestinal crypt epithelium and Death of immune cells by deletion of autoreactive T cells
• Examples of pathological apoptosis are Cell death induced by radiation, anti-cancer drugs, Viral diseases such as viral hepatitis, and organ atrophy secondary to duct obstruction seen in pancreas for example and Cell death in tumours
• Morphological Features of Apoptosis

  • Cell shrinkage
  • Chromatin condensation and fragmentation
  • Formation of cytoplasmic blebs and apoptotic bodies
  • Phagocytosis of apoptotic bodies by adjacent parenchymal cells or by macrophages
• Apoptosis can be activated by various death-triggering signals, such as lack of growth factor or hormone, positive ligand-receptor interaction and specific injurious agents.
• Apoptosis is the endpoint of an (energy-dependent) cascade of molecular events:

  • signalling pathways that initiate apoptosis
  • control and integration of positive and negative intracellular regulatory molecules
  • common execution phase, consisting of the actual death program
  • removal of dead cells by phagocytosis
• Necrosis

  • the functional and morphological changes that lead to cell death in a living cell/ tissue
  • degradative action of lysosomal enzymes
  • infarction is extensive necrosis, with large groups of necrotic cells due to impaired blood supply

  Different types of necrosis depending on nature of tissue and injurious agent
• • Coagulative necrosis occurs due to ischemia, where cell outlines are preserved due to limited enzymatic destruction.
  • Cell fragments and debris are removed by infiltrating macrophages and neutrophils. Macroscopically, tissue appears firm
  • Most common pattern of tissue necrosis in Heart, kidney, and spleen
• Liquefactive necrosis is characterised by the complete lysis of cells with the transformation of dead tissue into a liquid viscous mass and is typical of ischaemic necrosis in the brain.
• Fatty necrosis is associated with fat embolism from ruptured adipose tissue. The lipid droplets within the cells undergo hydrolysis resulting in the formation of free fatty acids which cause coagulation necrosis.
• Gangrenous necrosis is caused by bacterial infection and results in liquefaction of tissues. This type of necrosis is most commonly found in the extremities.
• Fibrous necrosis is characterized by fibrosis replacing areas of infarcted tissue. This type of necrosis is often found in bone marrow following radiation therapy.
• Hyaline necrosis is characterized by the presence of hyalinized collagen in place of normal parenchymal cells. It is often seen in renal biopsies.
• Caseous necrosis is characterized by the presence of large amounts of eosinophilic material that stains positively with acid-fast stain. It is typically seen in tuberculosis.
• Necrotizing granulomas are characterized by the presence of epithelioid histiocytes surrounding an area of necrosis. They can be seen in various diseases such as sarcoidosis and Crohn's disease.