Cell Injury And Death 1 Flashcards
Why does cell injury arise?
Severe changes in environment = cell adaptation, injury or cell death
Depends on type, severity, duration and tissue type
Response to injury
Adaptation —> injury (reversible) —> death (necrosis/apoptosis)
But can result in structural and functional changes
Cardiac myocytes response to cell injury (hypertension)
Increase workload (vascular resistance) Hypertrophy Increased weight and size of heart - workload is still too high - additional stress (atherosclerosis?) Cell injury and death (Myocardial Infarction)
Causes of cell injury
Hypoxia (deprivation of oxygen) Toxins - drugs, O2 Physical agents - trauma, temperature, pressure, electric currents Radiation Microorganisms Immune mechanisms Nutrition/diet - excess/deficiency Genetic and aging process
Types of hypoxia (HAIH)
Hypoxaemic - arterial oxygen content is low (high altitude/reduced absorption - lung disease)
Anaemic - Haemoglobin cannot carry O2 effectively (anaemia/carbon monoxide poisoning)
Isachaemic - interruption to blood supply (blockage/heart failure)
Histiotoxic - inability to utilise oxygen (oxidative phosphorylation fails - cyanide poison)
What things are toxic?
Glucose and salt in hypertonic solution Poison High oxygen Pollutant Insecticides/pesticides/herbicides Asbestos Alcohol Drugs Medicine
Immune system damage
Hypersensitivity - overly vigorous immune response, host tissue injured (hives)
Autoimmune - cannot distinguish between self and non self (attacks own cells eg Hashimotos)
Cell components susceptible to injury
Cell membranes - plasma and organelle
Nucleus - DNA
Proteins - structural and enzymes
Mitochondria - oxidative phosphorylation (ATP affected)
Low ATP effects on cell (reversible)
Mitochondria attacked:
Loss of ATP production via oxidative phosphorylation:
Na pump cannot work = influx of sodium water and calcium,
potassium leaks out (oncosis/swelling, loss of microvilli, blebs, ER swell, myelin figures)
Increased glycolysis = increase lactic acid - lower pH and glycogen (chromatin clump proteins denature)
Detachment of ribosomes = decreased protein synthesis, lipid deposition
Influx of calcium effects
Activation of: ATPase - lower ATP Phospholipase - decreased phospholipids Protease - membrane and cytoskeleton disrupted Endonuclease - nuclear chromatin damaged
Free radicals
ROS/RNS
Single unpaired electron in outer shell
Unstable - react with other molecules and produce further free radicals
Free radical examples
Superoxide (O2-) Hydrogen peroxide (H2O2) Hydroxyl radical (OH)
How are free radicals formed
Metabolism (ETC chain)
Radiation
Transition metals (Fenton reaction iron)
Drugs and chemicals (paracetamol metabolism, p450 system)
Inflammatory response - respiratory burst/oxidative burst
What do free radicals injury
Lipids - peroxidation damage membrane
Proteins - oxidation side chains/backbone, cross links, fragmentation
DNA - reaction with thymine, single strand breaks, mutagenic and carcinogenic
Bodies control of free radicals
Spontaneously decay
Free radical scavengers - vitamin ACE, metal carrier/storage proteins (transferrin)
Enzymes - superoxide dismutase (superoxide to hydrogen peroxide), catalase (hydrogen peroxide to water and oxygen), glutathione peroxidase
Body’s control of free radical damage (proteins)
cross link of proteins = fragmentation
Protein chaperones help folding
Heat shock proteins (hsp70/90) - mend misfolded proteins, maintain cell
Injured and dying cells change in appearance: (light microscope)
Cytoplasm - less pink from oncosis (swelling of water)
Nuclear changes (pyknosis - shrink, karyorrhexis - fragment, karyolysis - disappear)
Abnormal cellular accumulations
Electron microscope appearance of dying and injured cells:
reversible - blebs, swelling, ribosomes dispersed, ER/mitochondria swelling, clumping of chromatin, autophagy lysosomes
Irreversible - rupture of lysosomes and autolysis, defects in cell membrane, myelin figures, lysis of ER, nuclear changes
Oncosis
Cell death with swelling (prior to death)
Necrosis
Morphological changes that occur after a cell has died (12-24 hours) Can be: - coagulatative - liquefactive - caseous - fat - fibrinoid
Apoptosis
Programmed cell death
Coagulation necrosis
Protein denaturation
Solid organs
Cell architecture preserved
Liquefactive necrosis
Enzyme release
Loose tissues
Many neutrophils (infection)
Digestion of tissues
Caseous necrosis
Cheese like
Contains structures debris
Infection (TB especially)
Fat necrosis
Form chalky deposits
Usually occurs in pancreatitis - releases lipases, FA are released, form calcified deposits
Adipose blobs on slide
