32 Questions
What is the most damaging reactive oxygen species (ROS) responsible for damaging lipids, proteins, and DNA?
Hydroxyl
Which process is characterized by the tightly regulated intracellular program that requires synthesis and activation of signaling and effector proteins?
Apoptosis
What is one of the causes of apoptosis as an adaptive response to pathology?
Death of host cells that served their purpose
Which cellular process is implicated in both cancer cell death and survival?
Highly regulated macro-autophagy
What is the final common pathway in dystrophic calcification?
Formation of crystalline calcium phosphate
Where does metastatic calcification primarily occur?
Interstitial tissues of the gastric mucosa
Which type of necrosis is characterized by the architecture of dead cells being preserved?
Coagulative necrosis
What are examples of cellular adaptations to stress?
Hypertrophy, hyperplasia, atrophy, metaplasia
What are the definitions of reversible and irreversible cell injury?
Reversible: cell/tissue overcomes stress and resumes normal function; Irreversible: cell/tissue becomes damaged and eventually dies
What are the types of insults to tissues or cells mentioned in the text?
Hypoxia and ischemia, infection, inflammation, toxins/chemical agents, trauma
What does the cellular response to injury depend on?
Type of injury: Ischemic, ROS, Physical, Chemical, Inflammatory
What are examples of long-term extracellular damage patterns mentioned in the text?
Calcification, cellular inclusions
Which factor significantly influences cellular injury?
Duration and severity of the injury
What are the pathophysiologic consequences of reversible cell injury?
Cellular swelling, nuclear changes, accumulation of lipids
What are the mechanisms of necrosis?
ATP depletion, mitochondrial damage, calcium accumulation
What can calcium accumulation in the cytosol lead to?
Activation of destructive enzymes, direct activation of caspases, and release from mitochondria
What are the effects of membrane damage during ischemic injury?
Leaky membranes and detergent-like effects due to lipid breakdown products
Which family of proteins includes both anti-apoptotic and pro-apoptotic members?
BCL2
What is the major role of caspases 3 and 6 in the intrinsic pathway of apoptosis?
Activation by cytochrome C and execution of apoptosis
What is the adaptive response to injurious stimuli such as radiation and cytotoxic anticancer drugs?
Apoptosis
What is the microscopic pathology of apoptosis characterized by?
Cell shrinkage, chromatin condensation, and formation of apoptotic bodies
What leads to the release of pro-apoptotic molecules into the cytoplasm in the intrinsic pathway of apoptosis?
Increased permeability of the mitochondrial outer membrane
What is the mechanism of activation for necroptosis?
Binding of ligand to a receptor
Which process leads to the synthesis of p53 and subsequent apoptosis?
DNA damage
What is the primary function of caspases 8, 9, and 10 in apoptosis?
Activation of executioner caspases
What triggers the initiation of the extrinsic pathway of apoptosis?
Activation of plasma membrane death receptors
What is the morphological resemblance of necroptosis to necrosis?
Cell/organelle swelling
Which of the following is true about Fas receptor and Fas ligand interaction?
FasL binds to Fas, forming a binding site called Fas-associated death domain (FADD), which activates Caspases 8 and 10
What is the mechanism of activation for necroptosis?
Binding of ligand to a receptor, leading to RIP-kinase activation and MLKL phosphorylation
Which factor triggers apoptosis via the intrinsic (mitochondrial) pathway?
Lack of growth factor signal
What is the role of Bcl-2 and Bcl-x in apoptotic pathways?
Bcl-2 and Bcl-x can prevent apoptosis in the presence of growth factors
What is the main difference between necroptosis and necrosis?
Necroptosis is triggered by genetically programmed signal transduction, while necrosis is not
Study Notes
Apoptosis: Key Concepts and Pathological Mechanisms
- Apoptosis is a programmed cell death mechanism that eliminates potentially harmful self-reactive lymphocytes before or after maturation.
- Cell death can be induced by cytotoxic T cells as a defense mechanism against viruses and tumors, and it is also responsible for the rejection of transplanted cells.
- Apoptosis is an adaptive response to various injurious stimuli such as radiation and cytotoxic anticancer drugs, which can lead to cell death if repair mechanisms fail to cope with the damage.
- Pathological apoptosis can occur during the accumulation of misfolded proteins, ER stress, and unfolded proteins, as well as in cases of atrophy/involution of secretory tissues in parenchymal organs after duct obstruction.
- The microscopic pathology of apoptosis involves cell shrinkage, chromatin condensation, the formation of cytoplasmic blebs and apoptotic bodies, and the subsequent phagocytosis of apoptotic cells by macrophages.
- Apoptosis involves two major stages – initiation and execution – and two major types – the intrinsic (mitochondrial) pathway and the extrinsic (death-receptor) pathway.
- The intrinsic pathway results from cellular damage or lack of growth factors, leading to increased permeability of the mitochondrial outer membrane and the release of pro-apoptotic molecules into the cytoplasm.
- The release of pro-apoptotic proteins is controlled by the BCL2 family of proteins, which includes anti-apoptotic (Bcl-2, Bcl-X, Mcl-1) and pro-apoptotic (Bax, Bak, Bim, Bad, Bid, Puma, Noxa) members.
- ER stress, lack of growth signals, and DNA damage can increase pro-apoptotic proteins, while the lack of BH4 molecules and BH3-only molecules can activate the mitochondrial leak channel, leading to cytochrome C leakage and activation of caspases.
- The balance between anti-apoptotic and pro-apoptotic members of the BCL2 family determines whether a cell will pursue apoptosis.
- Key executioner caspases in the intrinsic pathway include caspases 3 and 6, which are activated by cytochrome C and play a crucial role in the execution of apoptosis.
- Apoptosis is a highly regulated process involving complex molecular mechanisms and can occur in response to various physiological and pathological stimuli.
Test your understanding of apoptosis with this quiz covering key concepts and pathological mechanisms. Explore the stages, pathways, and molecular regulation of this programmed cell death process, as well as its role in response to injurious stimuli and pathological conditions.
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