Cell Injury And Cell Death Flashcards
What are the causes of cell injury?
Hypoxic states
Ischemia: obstruction of blood flow
Anaemia: reduction in the number of RBC meaning less transport of O2.
Other causes
Physical agents: trauma, extremes of heat and cold, radiation.
Chemical agents: drugs, toxins
Infectious agents: bacteria, viruses, parasites, fungus
Free radicals
Genetic derangement: mutations, chromosomal abnormalities.
What will happen to the liver if excessive alcohol is used over a long period?
Fatty change in the liver whereby the cytoplasm has a foamy or bubbly appearance which can be recovered to normal.
Give three examples of how different cells show responses to injury.
Parenchymal cells are more sensitive than stromal cells
Brain and heart muscle cells are more susceptible to hypoxia and Ischemia, neuron dies in 3-4 minutes
Calf muscle tolerate 2-3 hours of Ischemia whereas cardiac muscle dies within 30 minutes.
What are the mechanisms of cellular injury and what are the etiological agents?
Deficiency of metabolites including oxygen, glucose, hormones
Mechanical disruption caused by trauma and osmotic pressure
DNA damage or loss by ionising radiation, chemotherapy, free radicals
Membrane damage by free radicals
Failure of membrane functional integrity due to damage to ion pumps
Blockage of metabolic pathways such as interruption of protein synthesis by diptheria toxin and respiratory poisons
Define the term ‘free radicals’.
An atom or group of atoms containing one or more unpaired electrons.
Name two free radicals.
Hydrogen peroxide
Superoxide anion
What are the consequences?
Membrane breakdown
DNA damage
Protein cross-linking
Loss of enzymatic activity
What are the two types of cell injury caused by ionising radiation?
Apoptosis and necrosis
How do free radicals get generated?
Ultraviolet light
Drugs and chemicals
Inflammation
Ionising radiation
Give three examples of antioxidants that reduce ROS.
Vitamin A & E - singlet oxygen
Catalase - hydrogen peroxide
Vitamin C - Superoxide radical
What are the cell responses to injury?
Adaptation - adjusting their structure and functions for various conditions.
Reversible injury: Hydropic degeneration (cloudy swelling) - accumulation of fluid to Na pump failure Fatty change - lipid accumulation due to ribosomal function failure
Irreversible injury:
Necrosis
Apoptosis
What is included in reversible injury? And give an example
Cellular swelling, large vacuoles in the cytoplasm Swelling of endoplasmic reticulum Swelling of mitochondria Disaggregation of ribosomes Chromatin clumping Cell blebs
Fatty liver can be reversed.
What are the differences between necrosis and apoptosis?
Necrosis Apoptosis
Number
of cells group of cells single cells
Cell size Enlarged Reduced
Nucleus. Pyknosis etc. fragmentation
Plasma
Membrane. Disrupted. Intact
Cellular Enzymatic digestion.Intact
Contents
Inflammation. Frequent. None
Pathological. Physiological
Describe what necrosis is.
Death of cells in living tissues characterised by the breakdown of the cell membranes, always a pathological condition.
What are the nuclear changes seen in necrosis?
Pyknosis: smaller deeply basophilic stained nucleus due to clumping of chromatin.
Karyorrhexis: nucleus breaks up into many smaller fragments scattered in cytoplasm
Karyolysis: nucleus disappears
What are the main types of necrosis?
Coagulative
General architecture well preserved
Nuclear changes
Most often results from interruption of blood supply
Liquifactive
Enzymatic liquefaction of necrotic tissue e.g. Necrosis in brain, pus formation in other tissues
Caseous
Dead cells persist as coarse granular eosinophilic debris
Shares features of coagulation and liquefaction necrosis
Most commonly seen in tuberculosis granuloma
Give one example of coagulative necrosis.
Gangrene.
What are the features of reversible and irreversible cell injury.
Reversible injury Decreased ATP levels Ion imbalance Swelling Decreased pH Fatty change
Irreversible injury Severe membrane damage Lysosomal rupture Extensive DNA damage (pyknosis, karyorrhexis, karyolysis) Cell lysis
What is physiological and pathological apoptosis?
Physiological
Formation of digits from the limb buds (embryogenesis)
To maintain cell population in tissues
Immune cell development e.g deletion of autoreactive T-cells
To remove damaged cells by virus or radiation
Wound healing
Pathological
In tumour, apoptosis process is disturbed
Cell loss due to viral illness
What are the causes of apoptosis?
Ionising radiation
Viral infection
Cell stress
Death receptors
Define labile cells.
Proliferate continuously
Short life span
E.g. Epithelial cells, haemopietic cells
Define stable cells
Conditional renewal of cells
Proliferate rapidly when cells are stimulated or lost
E.g. Liver, endocrine glands, bones
Define permanent cells
Only proliferate during fetal life but not after birth
E.g. Neurons, cardiac muscle
Define atrophy
Decrease in the size of an organ due to decrease in size of cells. Causes include: ageing, disuse of organs, malnutrition.
Define hypertrophy
Increase in the size of an organ due to increase in size of cells. Causes include: excessive hormone stimulation, increased use.
Define hyperplasia.
Increase in the size of an organ or tissue caused by an increase in the number of cells e.g. Glandular proliferation in the breast during pregnancy.
Define metaplasia.
Replacement of one differentiated cell type by another e.g. Columnar replaced by squamous epithelium in the bronchus of smokers.
Define aplasia.
It is a failure of cell production. E.g. during fetal development, aplasia results in absence of organ.
Define hypoplasia.
Cell production that is less extreme than aplasia. E.g. Partial lack of growth and maturation of gonadal structures in Turner syndrome and klinefleter’s syndrome.
What is autophagy?
Involves the degradation of a cells own components (damaged proteins, organelles or nuclear content) through the lysosomal machinery. Occurs within membrane-bound vesicles where lysosomal enzymes mix with substrates.
What are the causes?
Starvation, oxidative stress, irradiation, accumulation of misfolded proteins.
What are the three types of autophagy?
Macro-autophagy: the substrates are first packaged in an autophagosome and then this fuses with lysosome.
Micro-autophagy: here lysosome itself engulf the substrate.
Chaperone mediated autophagy: here receptors on the surface of lysosome selectively bind specific substances and allow them to be transported into lysosome.
What are the two pathways for apoptosis?
Extrinsic: triggered by death receptors on the cell surface.
Intrinsic: initiated at the mitochondrial level.
Apoptosis is not energy dependent. True or False?
False. Requires ATP.
Describe what happens in the extrinsic and intrinsic pathways.
Intrinsic: Initiated within cells. Often activated in response to signals resulting from DNA damage, loss of cell survival factors, or other types of severe cell stress. Normally pro-apoptotic proteins are released from the mitochondria to activate caspase proteases and trigger apoptosis, without these the cell cannot die.
Extrinsic: begins outside the cell through activation of pro-apoptotic receptors on the cell surface. These are activated by molecules known as pro-apoptotic ligands. Binding causes receptors to cluster and ultimately form a death-inducing signalling complex (DISC). After this, the same effector caspase machinery is adopted.
