2. Cell Injury, Cell Death and Adaptations Flashcards
Reversible cell injury
Cell swelling, fatty change, plasma membrane blebbing and loss of microvilli, mitochondrial swelling, dilation of the ER, eosinophilia (resulting from decreased cytoplasmic RNA)
Necrosis
Accidental cell death by increased cytoplasmic eosinophilia; nuclear shrinkage; fragmentation, and dissolution; breakdown of plasma membrane and organellar membranes; abundant myelin figures; leakage and enzymatic digestion of cellular contents
Patterns necrotic tissue
Coagulative (everywhere), liquefactive + colliquative (brain), gangrenous, caseous (typical for tuberculosis), fat (pancreatitis), and fibrinoid (arterial wall),
Apoptosis
regulated cell death to eliminate unwanted and irreparably damaged cells
enzymatic degradation of proteins and DNA
initiated by caspases and by rapid recognition and removal of dead cells by phagocytes
Intrinsic initiation of apoptosis (Mitochondrial)
Triggered by loss of survival signals, DNA damage and accumulation of misfolded proteins (ER stress)
Associated with leakage of proapoptotic proteins from mitochondrial membrane
There they trigger caspase activation
Inhibited by anti-apoptotic members of Bcl family (induced by survival signals (including growth factors)
Extrinsic initiation apoptosis (death receptor)
Elimination of self-reactive lymphocytes and damage by CTLs
Initiated by engagement of death receptors (members of TNF receptor family) by ligands on adjacent cells
Lethal signal from outside (FasL, TNF) triggers, thorugh receptor activation -> autocatalyc caspace activation
cytochrome c activates caspase 9
Phosphatidylserine flips to outside of cell membrane (signals other cells that cell can be taken up by other cells)
Necroptosis and pyroptosis
Necroptosis: regulated by particular signaling pathways (necrosis and apoptosis features)
Pyroptosis: can lead to release of proinflammatory cytokines and may initiate apoptosis
Autophagy
Adaptation to nutrient deprivation
Cells digest own organelles and recycle them to provide energy and substrates
Stress too severe: apoptosis
Hypoxia and ischemia
ATP depletion and failure of many energy-dependent functions
First reversible injury, then necrosis
Ischemia-reperfusion injury
Restoration of blood flow
Ischemic tissue exacerbates damage by increasing production of ROS and by inflammation
Oxidative stress
accumulation of ROS
damage cellular lipids, proteins, and DNA
associated with many initiating causes
Inflammation
associated with cell injury because actions of products of inflammatory leukocytes
hypertrophy
increased cell and organ size
in response to increased workload
induced by growth factors produced in response to mechanical stress or other stimuli
occurs in tissues incapable of cell division
hyperplasia
increased cell numbers
in response to hormones and other growth factors
occurs in tissues who are able to divide or contain abundant tissue stem cells
atrophy
decreased cell and organ size
result of decreased nutrient supply or disuse
associated with decreased synthesis of cellular building blocks and increased breakdown of cellular organelles and autophagy
proteosomal degradation
metaplasia
change in phenotype of differentiated cells
in response to chronic irritation (makes cells better able to withstand stress)
induced by altered differentiation pathway of tissue stem cells
may result in reduced functions or increased propensity for malignant transformation
replacement of one tissue by another tissue
Depositions of lipids
Abnormal deposits of lipids (and more)
result of excessive uptake or defective transport or catabolism
Fatty change and cholesterol deposition
fatty change
accumulation of free triglycerides in cells
results from excessive intake or defective transport (defects in synthesis of transport proteins)
manifestion of reversible cell injury
cholesterol deposition
result of defective catabolism and excessive intake
seen in macrophages and smooth muscle cells of vessel walls in atherosclerosis
deposition of proteins
reabsorbed proteins in kidney tubules; immunoglobulins in plasma cells
deposition of glycogen
in macrophages of patients with defects in lysosomal enzymes that break down glycogen (glycogen storage disease)
deposition of pigments
typically indigestible pigments (carbon, lipofuscin (breakdown of lipid peroxidation), or iron (overload (hemosiderosis)
Pathologic calcification
Deposition of caclium
Distrophic calcification at site of cell injury and necrosis
Metastatic calcification in normal tissues, caused by hypercalcemia (usually consequence of parathyroid hormone excess)
Combination of multiple progressive cellular alterations
accumulation of DNA damage and mutations
replicative senscence
defective protein homeostasis
aging
Damaging agent
Etiology (ie radiation): missense mutation
Pathogenesis: replacement nucleotide, incorrect amino acid, malfunctioning protein
Adaptation: cell or organ reacts to minimize damage impact
Cellular aging (telomere shortening)
DNA replicase cannot copy last piece of DNA
short telomere regions induce DNA damage response -> irreversible proliferation stop (cellular senscence)
Forced proliferation -> end-to-end joining of chromosomes -> chromosome breaks (aneuploidy, tumorigenesis)
telomerase can elongate telomeres (in stem cells and cancer cells)
