Cell Injury and Death Mechanisms

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Questions and Answers

What is the primary consequence of cellular swelling during early stages of injury?

Inability to maintain ionic and fluid homeostasis (correct)

Loss of membrane integrity

Nuclear dissolution without membrane loss

Inflammatory response activation

Which statement accurately describes necrosis?

It is characterized by nuclear shrinkage and chromatin condensation.

It is always a physiological process.

It involves the activation of apoptosis mechanisms.

It results in the leakage of cellular contents into the extracellular space. (correct)

What change occurs during fatty change in cells?

Disintegration of the cell membrane

Appearance of large lipid vacuoles in the cytoplasm (correct)

Increased activity of lysosomal enzymes

Decrease in mitochondrial function

Which mechanism primarily leads to irreversible cell injury?

Severe disruption of cellular membranes Signup and view all the answers

Which of the following is NOT a cause of cell damage?

Excessive nutrient intake Signup and view all the answers

Which characteristic is indicative of apoptosis as opposed to necrosis?

Membrane integrity preservation Signup and view all the answers

What is the initial physiological change observed in reversible cell injury?

Cellular swelling Signup and view all the answers

What pathological process occurs with necrosis that is not a feature of apoptosis?

Pathologic process activation Signup and view all the answers

Which factor is most likely to contribute to the hypertrophy of the endoplasmic reticulum in response to injury?

Toxic chemical exposure Signup and view all the answers

What type of cell death always results from severe damage to cellular membranes?

Necrosis Signup and view all the answers

What is the primary consequence of reduced activity of plasma membrane ATP-dependent sodium pumps?

Intracellular sodium accumulation Signup and view all the answers

What triggers the activation of enzymes due to increased cytosolic Ca2+ concentration?

Ischemia and certain toxins Signup and view all the answers

What is a key function of glutathione (GSH) peroxidases in cellular processes?

Oxidative damage protection Signup and view all the answers

Which of the following statements best describes reactive oxygen species (ROS)?

Their role in cell injury is well established. Signup and view all the answers

Which enzyme is significantly involved in accelerating the decay of superoxide free radicals?

Superoxide dismutase Signup and view all the answers

What is the expected outcome from the failure of oxidative phosphorylation?

Progressive depletion of ATP Signup and view all the answers

What effect does the intracellular accumulation of sodium have on cells?

Cell swelling Signup and view all the answers

What cellular change is associated with necrosis?

Uncontrolled cell lysis Signup and view all the answers

Which enzyme class is primarily responsible for causing membrane damage when activated by increased intracellular calcium?

Phospholipases Signup and view all the answers

Which pathological process can lead to fatty change in cells?

Inhibition of oxidative phosphorylation Signup and view all the answers

What is the primary characteristic of fatty change in cells?

Formation of lipid vacuoles Signup and view all the answers

Which of the following alterations is NOT characteristic of necrotic cells?

Hydropic change Signup and view all the answers

In the context of cell injury, what is the fate of necrotic cells?

Necrotic cells can persist or be digested Signup and view all the answers

What typically causes necrosis in cells?

Loss of membrane integrity and enzyme action Signup and view all the answers

Which of the following mechanisms best describes the typical cellular response to injurious stimuli?

Dependent on type, duration, and severity of injury Signup and view all the answers

What is a possible consequence of biochemical alterations due to cellular injury?

Depletion of cellular energy stores Signup and view all the answers

Which type of nuclear change is characterized by the fragmentation of chromatin?

Karyorrhexis Signup and view all the answers

What tissue type can generally withstand complete ischemia for several hours without irreversible injury?

Striated skeletal muscle Signup and view all the answers

Which of the following best describes the role of lysosomal enzymes in necrosis?

Digesting dead cells and cellular debris Signup and view all the answers

Which condition is least likely to occur as a result of necrosis?

Promotion of tissue regeneration Signup and view all the answers

Study Notes

Local Reactions of the Organism

Cell damage occurs when cells are stressed severely, unable to adapt, or exposed to damaging agents/intrinsic abnormalities
Reversible cell injury—early/mild injury; functional & morphologic changes are reversible if the damaging stimulus is removed
Cell death—continued damage; irreversible; two types: necrosis & apoptosis, which differ in mechanisms, morphology, and roles in disease and physiology
Necrosis occurs when damage to membranes is severe; enzymes leak out of lysosomes, enter cytoplasm, digest the cell, resulting in necrosis.
Cellular contents leak into extracellular space, causing an inflammatory reaction.
Necrosis is always a pathologic process
Apoptosis—when a cell lacks growth factors or has damaged DNA/proteins beyond repair; the cell kills itself.
Apoptosis is characterized by nuclear dissolution, but without loss of membrane integrity, not always caused by pathologic cell damage
Apoptosis does not elicit inflammation.

Causes of Cell Damage

Oxygen deprivation (hypoxia)
Chemical agents (e.g., CO, asbestos)
Infectious agents (e.g., fungi, bacteria)
Immunologic reactions (e.g., autoimmune reactions)
Nutritional imbalances
Physical agents (e.g., shock, temperature)
Aging

Types of Cell Damage

Reversible & irreversible cell damage
The graph shows stages of reversible & irreversible cell injury, from cell function to stages of death, indicating the severity of changes as well.

Reversible Injury

Two key changes: cellular swelling & fatty change
Cellular swelling—result of pump failure; inability to maintain ionic/fluid homeostasis.
Fatty change—occurs in hypoxic injury and other toxic/metabolic injuries; small or large lipid vacuoles in the cytoplasm appear
Injurious insults induce changes in cellular organelles (e.g., endoplasmic reticulum, or ER)
This may be an adaptive response with important functional consequences.

Cellular Swelling

First manifestation of injury to cells
Causes pallor (compression of capillaries), increased turgor, and increase in organ weight
Clear vacuoles within cytoplasm (distended & pinched-off segments of endoplasmic reticulum (ER))
Also called hydropic change or vacuolar degeneration

Fatty Change

Manifested by appearance of lipids in the cytoplasm.
Primarily found in fat-metabolizing cells (e.g., hepatocytes, myocardial cells), and is reversible
Plasma membrane alterations (blebbing, blunting, distortion of microvilli)
Endoplasmic reticulum (ER) dilation, ribosome detachment, and polysome dissociation
Chromatin clumping noted.

Irreversible Cell Damage

Necrosis—loss of membrane integrity & leakage of cellular contents, dissolution of injured cells.
Enzymes from dying cells & leukocytes digest the cells.
Associated with inflammation

Cytoplasmic Changes (necrosis)

Necrotic cells show increased eosinophilia
Nuclear changes occur; one of three patterns (due to DNA/chromatin breakdown): karyolysis, pyknosis, or karyorrhexis
Fates of necrotic cells may persist, be digested, or disappear

Mechanism of Cell Damage

Cellular response to injurious stimuli depends on injury type, duration, severity, status
Consequences depend on the injured cell's type, adaptability, & genetic makeup.
Cell injury results from abnormalities in several essential cellular components
Multiple biochemical alterations can be triggered by a single injurious insult
Examples: muscle tissues show different tolerance times to ischemia.

Mitochondrial Damage and Dysfunction

Failure of oxidative phosphorylation leads to progressive ATP depletion
Abnormal oxidative phos., leads to reactive oxygen species (ROS) formation

Influx of Calcium

Cytosolic free calcium normally maintained at low levels by calcium transporters (ATP-dependent)
Ischemia & certain toxins increase cytosolic calcium
Increased cytosolic calcium activates enzymes: phospholipases & proteases
These enzymes damage membranes and cytoskeletal proteins.

Oxidative Stress

Free radicals (single unpaired electron)
Reactive oxygen species (ROS)
Role in cell injury.

ROS (Reactive Oxygen Species) in Inflammation & Host Defense

Produced in phagocytic leukocytes (e.g., neutrophils, macrophages).
Used to destroy ingested microbes/substances.
NO (nitric oxide) is another reactive free radical.
Protective mechanisms exist to remove ROS: superoxide dismutases (SODs) & glutathione peroxidases (GSH).

Defective Membrane Permeability

Decreased phospholipid synthesis (due to low ATP levels)
Increased phospholipid breakdown
ROS (damaging effect)
Cytoskeletal abnormalities
Disturbances in membrane architecture, motility, and signaling resulting from changes.
Lipid breakdown products

3 Main reactions that cause cell damage

Lipid peroxidation of membranes
Changes/Cross-linking in proteins
DNA damage

Damage to DNA & Proteins

Cells repair DNA damage, but severe damage triggers apoptosis

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Description

This quiz focuses on understanding local reactions of organisms related to cell injury and death. It covers topics such as reversible and irreversible cell injury, necrosis, and apoptosis. Test your knowledge on the differences between these processes and their implications in disease and physiology.