Week 2 - Cell Adaptations, Injury and Death Flashcards
What are the cell survival requirements?
Constant energy supply, intact plasma membrane, efficient cellular activities, genomic integrity, controlled cell division, internal homeostatic mechanism
When does cell injury occur?
When the cell is unable to adapt through hyperplasia, hypertrophy, metaplasia, etc.
What are the types of lethal cell injury?
Necrosis, apoptosis
What are the types of sub lethal cell injury?
Fatty change (steatosis), hydropic change
How are mechanisms of cell injury classified?
According to causative agents and cellular targets
What can causative agents be?
Physical, chemical, biological
What are examples of physical causative agents?
Passive cell destruction, trauma and thermal injury, freezing, shearing forces
What is the mechanism of chemical causative agents?
Toxic to specific metabolic pathways
What are examples of biological causative agents?
Enzymes & toxins secreted by microorganisms, bacterial endotoxin, and viruses
How do bacterial endotoxins cause cell injury?
Metabolic products/secretions are toxic to surrounding cells
What is the effect of bacterial endotoxins?
They have a strong immune/inflammatory response, leading to damage to nearby cells.
How do viruses cause cell injury?
They cause infected cells to physically rupture, resulting in local tissue damage from the host immune response.
What can cellular targets be subdivided into?
Blockade of metabolic pathways, failure of membrane integrity, and DNA damage
What are examples of cell injury due to blockade of metabolic pathways?
Cellular respiration, glucose deprivation, inhibition of protein synthesis, loss of growth factor/hormonal stimulus, ischemia & reperfusion injury
What are examples of cell injury due to failure of membrane integrity?
Cell membrane damage, specific blockage of ion channels, failure of membrane ion pumps, free radical attack
What may cause membrane damage?
Complement mediated cytolysis or perforin mediated cytolysis
What may result from failure of membrane ion pumps?
Cells lysing
What are mechanisms of cell injury due to DNA damage?
Single/double strand break, base alteration, or cross linkage
What is a non-lethal cell injury due to DNA damage?
Inherited by daughter cells, leading to neoplastic transformation
What are features of irreversible cell injury?
Irreversible mitochondrial dysfunction, profound membrane dysfunction
What are examples of reversible cell injury?
Hydropic change, fatty change, autophagy
What causes hydropic change?
Interference with membrane structure, interruption of energy supplies to membrane exchange systems, leading to dysregulated ion and water movement in/out of the cell
What are features of hydropic change?
Pale and swollen cell cytoplasm, fluid accumulation
How do cells that have undergone hydropic change survive for weeks?
No membrane and internal structure rupture, enough membrane function is present, allowing metabolic processes to function.
Where are fatty changes mostly seen?
Liver, heart, kidney, which are cells with high lipid content/synthesis
What is the mechanism for fatty change?
Uncoupling of lipid from protein metabolism, accumulation of triglycerides, leading to fatty globule formation in cells
What are common causes of fatty changes/steatosis?
Toxins, chronic hypoxia, diabetes mellitus
What is the pathogenesis of fatty change?
Increased mobilization of free fatty acids & cellular uptake, increased conversion of free fatty acids to triglycerides, decreased oxidation of triglycerides to acetyl-CoA, decreased lipid acceptor proteins preventing export of formed triglycerides
What are causes of irreversible damage?
Free radicals, calcium ions, energy shortage, cell membrane dysfunction
What is apoptosis?
Programmed/controlled cell death
What is necrosis?
Uncontrolled cell death as a result of injury
What are the types of necrosis?
Coagulative, colliquative, caseous, gangrene, fibrinoid necrosis, fat necrosis
What are features of nuclear degeneration?
Karyopyknosis, karyorrhexis, karyolysis
What is a pyknotic nucleus?
A small, condensed, and intensely haematoxylin stained/basophilic nucleus of a necrotic cell
What is karyorrhexis?
Pyknotic nuclei fragmented into several particles
What is karyolysis?
Complete breakdown of the nucleus
What is the most common type of necrosis?
Coagulative necrosis
What is coagulative necrosis?
Protein denaturation/coagulation followed by repair and regeneration
What is colliquative/liquefactive necrosis?
Enzymatic digestion leading to cyst formation
What is gangrene?
Necrosis with putrefaction of tissues, leading to black deposits of iron sulphide from degraded hemoglobin
What are the causes of gangrene?
Bacterial infection, poor blood supply
What is dry gangrene?
Gangrene affecting the toes
What is wet gangrene?
Gangrene affecting the bowel
What is fibrinoid necrosis?
Necrosis characterized by the deposition of fibrin-like protein in tissue
What are apoptotic inhibitors?
Growth factors, extracellular matrix (ECM), sex steroids, some viral proteins
What are apoptotic inducers?
Growth factor withdrawal, loss of ECM attachment, some viruses, free radicals, ionizing radiation, DNA damage, ligands binding death receptors
What are the pathways of apoptosis?
Mitochondrial (intrinsic) pathway or death receptor (extrinsic) pathway
What are the phases of apoptosis?
Activation of caspase 8 (initiator), cleaves executioner caspases (caspase 3 & 7), degradation of cellular components, caspases activate DNAse (fragments DNA), nucleus shrinks and fragments, cell shrinks, changes to membrane induce phagocytosis, if cell not phagocytosed, forms apoptotic body
What are stimuli of the intrinsic pathway?
Growth factors, biochemical stress, DNA damage
What does the intrinsic pathway of apoptosis cause?
Alterations in relative levels of pro and anti-apoptotic members of the Bcl-2 family
What is Bcl-2?
A protein that inhibits apoptosis
What is Bax?
A protein that stimulates apoptosis
What is the extrinsic pathway of apoptosis?
Death receptors bind onto the cell surface, stimulating caspases
What are death receptors?
TNF receptor 1, Fas
What are causes of pathological apoptosis?
Radiation, chemotherapy, drugs
What is asymmetric cell division?
One daughter cell progresses along the differentiation pathway and another replaces the parent cell
What is the healing process?
Fibrin scab protects underlying skin, cells proliferate and spread as a thin sheet until the defect is covered, replaced from bottom up
What is the process of repair?
Endothelial cells form vascular channels, fibroblasts proliferate and secrete collagen and other ECM proteins, combination of capillary loops and myofibroblasts leads to granulation tissue
What are the consequences of large wound skin repair?
Loss of sweat glands and hair, keloid (raised) scar
What stimulates skin repair of large wounds?
Cytokines and growth factors
What factors affect repair?
Damage to fetus, old age, nutritional deficiencies, corticosteroids, disseminated malignancy, local ischemia, diabetes mellitus
What is transmural infarction?
Myocardial infarction that involves full thickness of myocardium, extending through the muscularis propria to the serosa
