88 Questions
What is the primary difference between apoptosis and necrosis?
Apoptosis is programmed cell death, while necrosis is unregulated cell death in response to external factors such as toxins, trauma, and infection.
What is the result of oxygen deprivation in cells, and what are some possible causes of this condition?
Oxygen deprivation, or hypoxia, can result in a reduction in aerobic oxidative respiration, leading to cellular injury or death. Possible causes include reduced blood flow, inadequate oxygenation of the blood, and decreased blood oxygen-carrying capacity.
What is the effect of cellular swelling on ion concentrations and water influx?
Cellular swelling causes changes in ion concentrations and water influx, leading to a depletion of energy stores in the form of adenosine triphosphate (ATP).
What is the process by which intracellular components, including organelles, are packaged into miniature membrane pockets?
apoptosis
What type of necrosis is typically caused by ischemia or infarction and tends to occur in tissues such as the heart, kidney, and adrenal glands?
Coagulative necrosis
What are some examples of physical agents that can cause cellular injury?
Examples of physical agents that can cause cellular injury include mechanical trauma, extremes of temperature, sudden changes in atmospheric pressure, radiation, and electric shock.
What are the primary differences between necrotic cell death and apoptotic cell death?
Necrotic cell death involves swelling of the endoplasmic reticulum, membrane breakdown, and release of cellular contents, leading to an inflammatory response. Apoptotic cell death, on the other hand, involves chromatin condensation, DNA cleavage, and membrane blebbing, resulting in a more controlled and regulated process.
What is the result of the denaturation of intracellular proteins and enzymatic digestion in necrotic cells?
Loss of membrane integrity and leakage of cellular contents
What is the role of pro-inflammatory macrophages in necrotic cell death?
Pro-inflammatory macrophages are recruited in response to necrotic cell death, eliciting an inflammatory response and leading to the degradation of dead cells.
What is the condition that occurs when a person experiences an injury to an area of fatty tissue, resulting in the fat being replaced with the oily contents of fat cells?
Fat necrosis
What is the effect of ischemia on cellular injury and death?
Ischemia, or reduced blood flow, can result in oxygen deprivation, leading to cellular injury and death.
What is the term for the death of tissue due to a lack of blood flow?
Gangrenous necrosis
What are some nuclear changes that occur during apoptotic cell death?
During apoptotic cell death, chromatin condenses, and DNA is cleaved into discreet 200 base pair units.
What is the process by which phagocytes engulf and degrade apoptotic bodies?
Phagocytosis
What is the type of necrosis that involves the transformation of cellular mass into a liquid viscous mass, commonly associated with bacterial and fungal infections?
Liquefactive necrosis
What is the term for the morphologic appearance of necrosis resulting from denaturation of intracellular proteins and enzymatic digestion?
Morphology of necrosis
What is the earliest histologic evidence of necrosis, and how long does it take to become apparent?
The earliest histologic evidence of necrosis may not become apparent until 4 to 12 hours.
What is the characteristic appearance of cytoplasm in necrotic cells, and what is the cause of this change?
The cytoplasm becomes vacuolated and appears moth-eaten, due to the digestion of cytoplasmic organelles by enzymes.
What are myelin figures, and how do they form in necrotic cells?
Myelin figures are large, phospholipid masses derived from damaged cell membranes, and they form when dead cells are replaced by these structures.
What is the outcome of karyolysis, and what is the underlying mechanism?
Karyolysis is the fading of chromatin, which appears to reflect loss of DNA due to enzymatic degradation by endonucleases.
What is the effect of mitochondrial damage on oxidative phosphorylation in coagulative necrosis?
Mitochondrial damage leads to a significant decrease in oxidative phosphorylation.
What is the role of anaerobic glycolysis in coagulative necrosis, and how does it contribute to cellular damage?
Anaerobic glycolysis is enhanced, leading to an accumulation of lactic acid and a decrease in cellular pH, which contributes to chromatin clumping.
What is the effect of ischemia on cellular swelling, and what is the underlying mechanism?
Ischemia leads to cellular swelling due to the accumulation of calcium and sodium ions, combined with water retention.
What is the outcome of karyorrhexis, and what is the characteristic feature of this nuclear change?
Karyorrhexis is the fragmentation of the pyknotic nucleus, and it is characterized by the breaking up of the nucleus into smaller fragments.
What is the eventual outcome of the breakdown of membranes, cytoskeletal proteins, and genomic and mitochondrial DNA?
Necrosis
What is the role of caspase 9 in the intrinsic apoptotic pathway?
Cleaves Caspase 3, 6, and 7, initiating the caspase cascade
What is the significance of apoptosis during the development of an embryo?
It is necessary for the removal of webbing between appendages
What is the effect of ischemia on cellular injury and death?
It leads to necrosis, particularly coagulative necrosis
What is the outcome of cellular swelling due to an increase in ion concentrations and water influx?
Necrosis
What is the characteristic feature of nuclear changes during apoptotic cell death?
Fragmentation of DNA and nucleus
What is the role of initiator caspases in the apoptotic pathway?
They transmit signals from extracellular signals and initiate the caspase cascade
What is the significance of apoptosis in adult humans?
It occurs continuously to maintain tissue homeostasis, with the rate of apoptosis equal to the rate of cell renewal and growth
What is the mechanism by which cytochrome C is released from the mitochondrial membrane during apoptosis?
Cytochrome C is released from the mitochondrial membrane during apoptosis due to cardiolipin oxidation via cardiolipin-specific oxygenase, which is stimulated by mitochondrial ROS.
What is the role of Apaf-1 in the formation of the Apoptosome?
Apaf-1 is an adaptor protein that binds to cytochrome C to form the Apoptosome, which is necessary for the progression of the apoptotic signal.
What is the function of caspase 3 in the execution phase of apoptosis?
Caspase 3 cleaves ICAD to produce CAD, which is responsible for the fragmentation of DNA in a controlled manner.
What is the role of Gelsolin in the execution phase of apoptosis?
Gelsolin is a protein that mediates cytoskeletal reorganization and disintegration during the execution phase of apoptosis.
What is the consequence of cardiolipin oxidation on cytochrome C binding?
Cardiolipin oxidation releases cytochrome C from its binding to the mitochondrial membrane, allowing it to participate in the apoptotic signal.
What is the role of IAPs in regulating the apoptotic signal?
IAPs (Inhibitor of Apoptosis Proteins) regulate the apoptotic signal by inhibiting the activity of caspases.
What is the consequence of cytochrome C binding to Apaf-1?
Cytochrome C binding to Apaf-1 promotes the formation of the Apoptosome, which is necessary for the progression of the apoptotic signal.
What is the role of procaspase 9 in the formation of the Apoptosome?
Procaspase 9 is activated to form caspase 9, which is necessary for the formation of the Apoptosome.
What is the function of caspase 9 in the intrinsic apoptotic pathway?
Cleaves and activates caspases 3, 6, and 7, initiating the caspase cascade
What is the outcome of DNA fragmentation during apoptosis?
Genomic DNA degradation
What is the role of initiator caspases in the apoptotic pathway?
Initiation of the caspase cascade
What is the result of cytoskeletal reorganization during apoptosis?
Disruption of the cytoskeleton
What is the role of cytochrome C in the intrinsic apoptotic pathway?
Formation of the Apoptosome
What is the outcome of Apoptosome formation?
Execution of apoptosis
What is the function of caspase 3?
Involved in the activation cascade of caspases responsible for apoptosis execution
What is the role of procaspase 9 in the formation of the Apoptosome?
Formation of the Apoptosome
What is the primary function of caspase 7 in the apoptotic pathway?
Activation of sterol regulatory element binding proteins
What is the result of poly(ADP-ribose) polymerase (PARP) cleavage?
DNA fragmentation
Which protein is cleaved by caspase 3 in the execution phase of apoptosis?
Gelsolin
What is the role of FADD in the extrinsic apoptotic pathway?
Transmission of the death signal through the cytoplasm
What is the function of TRADD in the TNF receptor-mediated apoptotic pathway?
Transmission of the death signal through the cytoplasm
What is the role of Bax and Bak in the intrinsic apoptotic pathway?
Activation of pro-apoptotic proteins
What is the result of the binding of Fas ligand to the Fas receptor?
Transmission of the death signal through the cytoplasm
What is the primary effect of chromatin condensation during apoptotic cell death?
Packaging and degradation of DNA
What is the role of Apaf-1 in the intrinsic apoptotic pathway?
Formation of the Apoptosome
What is the typical size of DNA fragments resulting from DNA cleavage during apoptosis?
200 base pair units
What is the primary role of caspase 3 in the apoptotic pathway?
Execution of the apoptotic signal
What is the effect of cytoskeletal reorganization during apoptosis?
Formation of membrane blebs
What is the role of Apaf-1 in the apoptotic pathway?
Formation of the apoptosome
What is the consequence of procaspase 9 activation during apoptosis?
Activation of caspase 3
What is the role of gelsolin in the apoptotic pathway?
Cleavage of cytoskeletal proteins
What is the consequence of cardiolipin oxidation during apoptosis?
Release of cytochrome C from the mitochondria
What is the role of cardiolipin oxidation in apoptotic signaling?
It releases cytochrome C from its anchor, allowing for progression of the apoptotic signal
What is the primary function of caspase 3 in the execution phase of apoptosis?
It cleaves ICAD, producing CAD, which is responsible for DNA fragmentation
What is the role of Apaf-1 in the intrinsic apoptotic pathway?
It requires the addition of cytochrome C to form the Apoptosome
What is the consequence of cytochrome C binding to Apaf-1?
It activates procaspase 9, leading to the progression of the apoptotic signal
What is the role of Gelsolin in the execution phase of apoptosis?
It mediates cytoskeletal reorganization and disintegration
What is the role of IAPs in regulating the apoptotic signal?
They inhibit the activation of procaspase 9
What is the consequence of procaspase 9 activation?
It leads to the activation of caspase 3, allowing for DNA fragmentation
What is the role of caspase 9 in the intrinsic apoptotic pathway?
It is required for the formation of the Apoptosome through the intrinsic pathway
What is the term for the transformation of cellular mass into a liquid viscous mass commonly associated with bacterial and fungal infections?
Liquefactive necrosis
What is the process by which intracellular components, including organelles, are packaged into miniature membrane pockets called apoptotic bodies?
Apoptosis
What is the term for the death of tissue due to a lack of blood flow?
Gangrenous necrosis
What is the outcome of the denaturation of intracellular proteins and enzymatic digestion in necrotic cells?
Leakage of cellular contents
What is the condition that occurs when a person experiences an injury to an area of fatty tissue, resulting in the fat being replaced with the oily contents of fat cells?
Fat necrosis
What is the term for the morphologic appearance of necrosis resulting from denaturation of intracellular proteins and enzymatic digestion?
Morphology of necrosis
What is the process by which phagocytes engulf and degrade apoptotic bodies?
Phagocytosis
What is the term for a type of necrosis characterized by accumulation of amorphous, basic, proteinaceous material in the tissue matrix?
Fibrinoid necrosis
What are the 2 main categories of Caspases?
Procaspase – Non-active caspases containing inhibitory domains Cytochrome C – Key protein in progression of intrinsic apoptotic pathway
What are the exact initiator caspases?
Caspase-8 and caspase-9 Capases 2 and caspase 10
What is the role of initiator caspases in the cell?
They initiate the caspase cascade, triggering the apoptotic pathway.
What are the roles of Executioner caspases?
Cleaving and activating other caspases, and degrading cytoskeletal and nuclear proteins, ultimately leading to apoptotic cell death
What is the main characteristic of the Extrinsic Death receptor mediated pathway?
Involves the activation of caspase-8
What is the primary mechanism of the intrinsic - mitochondria mediated pathway of apoptosis?
Release of cytochrome c
What are the key proteins involved in the Intrinsic Mitochondria Mediated pathway?
Cytochrome c, Apaf-1, and Caspase-9
Which Bcl-2 family proteins are involved in the intrinsic - mitochondria mediated pathway?
Bcl-xL and Bcl-2/ bAX AND Bak
Study Notes
Apoptosis and Necrosis
- Apoptosis: programmed cell death, a tightly regulated suicide program controlled by specific genes
- Necrosis: unregulated cell death in response to external factors such as toxins, trauma, and infection, leading to release of cellular machinery into surrounding tissues
Cellular Injury
- Caused by:
- Oxygen deprivation (hypoxia)
- Physical agents (mechanical trauma, extreme temperatures, radiation, electric shock)
- Chemical agents and drugs
- Infectious agents
- Immunologic reactions
- Genetic derangements
- Nutritional imbalances (protein-calorie and/or vitamin deficiencies, overnutrition)
Necrotic Cell Death
- Stages:
- Swelling of the endoplasmic reticulum and membrane blebing
- Plasma membrane breakdown and cell contents leak out
- Organelle breakdown and leakage of contents
- Pro-inflammatory macrophage recruitment and inflammatory response
- Release of "volatile" intracellular components, leading to damage to surrounding cells
- Neutrophil infiltration to degrade dead cells
Apoptotic Cell Death
- Stages:
- Chromatin condenses and DNA cleaves into 200 base pair units
- Membrane blebbing
- Release of cytochrome C from mitochondria into cytosol
- Formation of an Apoptosome and activation of effector caspases
- Execution phase: activation of caspase 3, cleavage of ICAD, and fragmentation of DNA
- Apoptotic bodies are engulfed by phagocytes and recycled
Types of Necrosis
- 6 types:
- Coagulative necrosis: typically caused by ischemia or infarction, occurs in tissues such as heart, kidney, and adrenal glands
- Liquefactive necrosis: involves transformation of cellular mass into a liquid viscous mass, commonly associated with bacterial and fungal infections
- Caseous necrosis: tissue maintains a cheese-like appearance, dead tissue appears as a soft and white proteinaceous dead cell mass
- Fat necrosis: occurs when a person experiences an injury to an area of fatty tissue, resulting in fat being replaced with oily contents of fat cells
- Fibrinoid necrosis: characterized by accumulation of amorphous, basic, proteinaceous material in the tissue matrix
- Gangrenous necrosis: death of tissue due to a lack of blood flow
Morphology of Necrosis
- Result of denaturation of intracellular proteins and enzymatic digestion
- Necrotic cells unable to maintain membrane integrity, leading to leakage of contents and potential inflammation in surrounding tissue
- Enzymes that digest necrotic cells derived from lysosomes of dying cells and leukocytes
- Digestion of cellular contents and host response may take hours to develop
Quiz about programmed cell death (apoptosis) and necrotic cell death in response to cell injury, including causes and effects on surrounding tissues.
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