5.1 Flashcards

Question

What are the two types of cell death?

Answer 1

1. Apoptosis = programmed cell death by the immune system. It is a controlled process that the cell initiates in response to internal cues or external signals. It is a necessary aspect of development and cellular turnover. 2. Necrosis = cell death caused by TRAUMA --> external factors such as injury, infection, or toxins, leading to the uncontrolled destruction of cell structures.

Answer 2

1. Morphologically: - Apoptosis = cells shrink, condense, and their parts are neatly packaged into vesicles called apoptotic bodies. Apoptotic bodies are phagocytosed by other cells therefore = preventing inflammation. - Necrosis = cells swell, burst, and release their contents into the surrounding tissue therefore = cause inflammation. 2. Roles in disease: - Apoptosis = plays critical roles in both normal physiological processes (e.g. embryonic development and immune function) and disease (e.g. cancer, where its dysregulation can lead to uncontrolled cell growth). - Necrosis = is associated with diseases where damage and inflammation are prevalent. e.g. heart attacks (myocardial infarction) and strokes.

Answer 3

Occurs when the extent, type or duration of the stress or injury surpasses the cell's ability to adapt and recover.

Answer 4

1. Cell-related factors (factors intrinsic to the cell): - Genetics --> variations in the cytochrome P450 enzymes, can affect how cells respond to toxins, potentially making some cells more susceptible to damage. - Adaptability --> cells' ability to adapt to stress through mechanisms like upregulating stress responses or repair pathways influences their survival. - Cell types --> different types of cells have varying tolerances to ischemia (oxygen deprivation). Skeletal muscle cells can withstand 2-3 hours of ischemia, cardiac muscle cells around 20-30 minutes, and neurons only 3-5 minutes. - State --> metabolic state of the cell, such as its glycogen stores, can affect its ability to undergo anaerobic glycolysis and survive during periods of low oxygen. 2. Injury-related factors (nature of the injury itself): - Type of injury --> chemical, physical, or biological = all have diff effects. - Duration --> longer exposure time = increases likelihood of irreversible damage. - Severity --> more severe injuries = overwhelm defensive/repair systems. - Exposure --> short, low dose VS long, high dose to toxins or hypoxia.

Answer 5

The study of the structure, shape, and appearance of cells and tissues to assess their health, function, and response to various conditions including disease and injury.

Answer 6

- Allows scientists and medical professionals to observe and diagnose diseases/damage in cells and tissues. - By examining the gross/microscopic appearance of cells and tissues = pathologists can infer the physiological and pathological conditions affecting the tissues.

Answer 7

- Most cells = are naturally transparent. - Staining procedures make cells visible under a microscope. - Haematoxylin and eosin (H&E) staining: - Haematoxylin stains acidic or basophilic structures, including nucleic acids, giving the nucleus a purplish-blue colour. Eosin stains basic or acidophilic structures, such as most proteins, pink or red, enhancing contrast and detail in cytoplasmic components.

Answer 8

1. reduction in the conc of O2 to the mitochondria (hypoxia). 2. decreased ATP production --> bc mitochondria require O2 to produce ATP efficiently, therefore, decreased O2 = decreased ATP production. ATP = essential for the synthetic (building up) and degradative (breakdown) metabolic processes. 3. damage to mitochondria --> ongoing hypoxia and reduced ATP production = stress mitochondria and lead to structural and functional damage. Damaged mitochondria = less efficient at producing ATP (EXACERBATING ENERGY CRISIS WITHIN CELLS). 4. Influx of Ca^2+ --> Ca2+ levels = tightly regulated bc Ca2+ ions play a crucial role in activating various cellular enzymes. Disruptions in energy production = impair the cell's ability to regulate Ca2+ --> leads to an influx. High intracellular Ca2+ levels = activate enzymes that DEGRADE cellular components (further damaging the cell!!). 5. Accumulation of reactive oxygen species (ROS) --> ROS = by products of normal cellular metabolism (mostly aerobic respiration). Under normal conditions = cells have mechanisms to scavenge these molecules and prevent DAMAGE. HOWEVER, in stressed/damage = increased ROS = overwhelm these mechanisms --> leading to oxidative stress and damage to macromolecules (e.g. lipids, proteins, nucleic acids). 6. Membrane damage --> accumulation of ROS (and other stressors like high Ca2+ levels) = damage to various cellular membranes - including mitochondrial membrane, plasma membrane, and lysosomal membranes. DAMAGE = impairs func and integrity of these membranes, disrupting cellular homeostasis and leading to cell death if severe. 7. DNA and Protein Damage --> damaged membranes and oxidative stress = lead to direct damage of DNA and proteins. When DNA and proteins = damaged beyond repair --> triggers programmed cell death mechanisms (apoptosis)/lead to necrotic cell death if the damage is extensive/sudden.

Answer 9

Mechanism of injury involving the retention of H2O = typically relates to disruptions in ATP-dependent ion channels. - ATP-dependent Ion Channels = use ATP to actively transport ions (e.g. Sodium and Potassium) across the cell membrane. This maintains osmotic balance and cellular volume. REDUCTION IN ATP DUE TO DAMAGE = malfunctioning of these ion channels - therefore, results in the inability to properly regulate ion gradients across the cell membrane. - Water retention = occurs because of ion pump failure. Sodium accumulates in the cell, therefore, water travels down the concentration gradient to try and balance, therefore leads to cell swelling/bursting. - Ca2+ ion homeostasis = in normal cells, Ca2+ play NB role in numerous cellular processes: signalling, muscle contraction, and enzyme activity. Proper regulation of Ca2+ levels w/in cells = essential for cellular health and function. DISRUPTION = seen when cell injury affects Ca2+ channels or pumps - lead to an overload of Ca2+ in cells. Overload of Ca2+ = activate destructive enzymes --> further damaging cellular structures and exacerbating cell injury. NOTE: excessive Ca2+ interferes with with ETC (which is crucial with ATP production). When ETC effected by Ca2+ interference - therefore it begins to leak e- --> leaked e- can react with oxygen to form ROS.

Answer 10

1. Reduced Oxygen/Nutrients to the mitochondria cause damage. Additionally, toxins (e.g. cyanide) inhibit the ETC. 2. Decreased ATP production bc of mitochondrial damage - ATP = critical fro numerous cell funcs including energy for active transport mechanisms. 3. Ion channel dysfunction = ATP-dependent ion channels fail without sufficient ATP - disrupting the ion balance across the cell membrane. 4. Ion imbalance = Ca2+ and Na+ accumulate inside the cell, while K+ exits the cell. This solute imbalance attracts water into the cell osmotically. 5. Cell and ER swelling = influx of H2O causes cell and the ER to swell. This can lead to the membrane 'blebbing'/forming blisters. 6. Anaerobic glycolysis = in response to hypoxia, hepatocytes increase anaerobic glycolysis --> leading to rapid glycogen depletion and lactic acid build up. 7. Acidic intracellular Environment - accumulation of lactic acid lowers the intracellular pH, one of the 1st morphological changes visible under a microscope as nuclear chromatin clumping (???). 8. Protein synthesis disruption = lower pH and cell stress = leads to ribosomes detaching from the rough ER - THEREFORE, reducing protein synthesis, and potentially leading to further blebbing.

Answer 11

Disrupt cellular function in several critical ways. 1. Opening of the mitochondrial permeability transition pore (MPTP) --> allows solutes to move freely across the mitochondrial membrane (disrupting mito membrane potential and impairing the mitochondria's ability to generate ATP). 2. Decreased efficiency of aerobic respiration --> reduces ATP production and also lead to increased production of ROS. ROS = damaging to cellular components and can exacerbate mito damage. 3. Release of cytochrome C from the inner membrane space into the cytoplasm can occur if mito damaged. Once in cytoplasm, CC-C = activate pathways that lead to apoptosis/programmed cell death.

Answer 12

- Ca2+ = deliberately kept low inside of the cell. - This is maintained using ATP-dependent transport (channels, pumps, etc). - Ca2+ = can activate phospholipases, proteases, endonucleases and ATPases. - As a consequence, when Ca2+ conc increases in the cell --> membrane and nuclear damage occurs. - Ca2+ can also activate caspases which can induce APOPTOSIS.

Answer 13

- ROS = oxygen-derived free radicals (have unpaired e- in outer orbital, unstable, and reactive, and attack nucleic acids, proteins, and lipids). - ROS = by-product of respiration and produced by phagocytic leukocytes. Removed by scavengers (catalase). - If cell makes an increased number of ROS/scavengers aren't working --> ROS increases and cell = under oxidative stress. EFFECTS OF ROS: - Peroxidation of lipids (plasma membrane and organelle membranes). - Oxidative modification of proteins - change the active site of enzymes, change protein structure, or increase proteasomal degradation of damaged proteins. - Lesions in DNA - causes cross-linking and strand breaks. All of the above = moving towards membrane damage.

Answer 14

- DNA damage can be caused by drugs, radiation, or oxidative stress (ROS) - Protein damage/misfolding can be caused by inherited mutations and external triggers. Initiates suicide program if it cannot be repaired (apoptosis)

Answer 15

- Oxygen deficiency - Interferes with aerobic oxidative respiration - Caused by ischemia (loss of blood supply to tissue), pneumonia (inadequate oxygenation), blood loss/anaemia, CO poisoning.

Answer 16

Increased Staining with Eosin (Eosinophilia): In hypoxic conditions, heart cells (cardiomyocytes) undergo protein denaturation and digestion of RNA. Normally, RNA stains blue with hematoxylin due to its basophilic properties, but loss of RNA leads to less blue staining. The denatured proteins stain more intensely with eosin, making the cytoplasm appear more pink—a condition known as eosinophilia. Reduced Nuclei (Less Haematoxylin Staining): The nuclei may appear less prominent or reduced in number, which can be detected by lighter staining with hematoxylin. This change indicates potential nuclear degradation or damage, common in dying cells. Oedema (Swelling): Hypoxia can cause fluid accumulation in tissues (oedema), which leads to swelling. In the heart, this results in increased gaps between cardiomyocytes, observable in histological samples. Inflammatory Cells (Purple Staining): The presence of inflammation in response to tissue injury is marked by the infiltration of inflammatory cells, which are stained purple with hematoxylin. This is a typical response to cellular damage and necrosis. Intracellular Proteins Leak Through Damaged Cell Membrane: Due to the compromised integrity of the plasma membrane under hypoxic stress, intracellular proteins can leak out of the cardiomyocytes. Cardiac Specific Enzymes: The leakage of specific cardiac enzymes like the cardiac isoform of creatine kinase (CK-MB) and troponin into the bloodstream is a key marker used clinically to diagnose cardiac injury. These proteins are normally found within the cells, and their presence in blood typically indicates damage to the heart muscle. Serum Levels Reflect Tissue Injury: Myocardial Infarction: In cases of myocardial infarction, an irreversible injury, there is significant damage to the cardiac tissue, leading to loss of plasma membrane integrity. This allows cardiac enzymes to enter the bloodstream, where their levels can be measured. Angina: In contrast, angina is typically considered a reversible injury where the plasma membrane remains intact. However, severe or prolonged angina can stress cardiomyocytes enough to cause mild enzyme leakage, detectable in some cases.

Answer 17

Accumulations within cells occur when a cell is unable to metabolize a substance - causing it to accumulate within the cytoplasm, organelles, or nucleus of the cell. When do they occur? 1. Normal endogenous substance is produced at a normal/increased rate, but the rate of metabolism is inadequate to remove it. 2. Accumulation due to defects in folding, packaging, or degradation, typically due to mutation. 3. Failure to degrade due to enzyme deficiency (mutation). 4. Deposition of exogenous substance.

Answer 18

- Water accumulation in cells when the cell membrane permeability is increased, or ion pumps fail- Hydropic swelling (pale vacuolated cytoplasm) - Injury to cells involves fat metabolism can lead to accumulation of triglycerides- Steatosis or fatty change (accumulation of lipids displaces the nucleus) - The accumulation of cholesterol and cholesterol esters in macrophages and smooth muscle cells in the intimal layer of blood vessels gives these cells a foamy appearance (foam cells) aggregates of foam cells form atherosclerotic plaques - Exogenous pigments such as carbon found in air pollution are taken up by alveolar macrophages- the accumulation of carbon in tissue is known as anthracosis - Endogenous pigments include lipofuscin (polymers of lipids/ phospholipids/ proteins) a sign of free radical injury and lipid peroxidation - Endogenous pigments include hemosiderin, a major storage form of iron that accumulates in tissue when iron is in excess- accumulates as golden-brown granules (haemochromatosis) - Intracellular accumulation of proteins gives a homogenous, glassy pink appearance under H&E staining described as hyaline changeaggregation of specific proteins is associated with specific diseases and called proteinopathies of protein-aggregation diseases

5.1 Flashcards

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