Cell Injury and Death Mechanisms

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Questions and Answers

What characterizes necrosis as opposed to apoptosis?

Occurs in normal physiological conditions

Is a reversible form of cell injury

Is associated with cell swelling and organellar breakdown (correct)

Is a form of programmed cell death

Which of the following conditions can cause cell injury through hypoxia?

Inadequate oxygenation of the blood (correct)

Electric shock

Excessive temperature exposure

Sudden changes in atmospheric pressure

What aspect of cell injury is influenced by the type of cell and its health status?

Duration of the injurious stimulus

Severity of the injury

Presence of physical agents

Response to injurious stimuli (correct)

Which of the following intracellular systems is NOT vulnerable to injury?

Cellular energy production from glycolysis Signup and view all the answers

What role do calcium transporters play in cellular injury?

Maintaining low levels of cytosolic free calcium Signup and view all the answers

Which of the following is a common cause of cell injury caused by nutritional imbalances?

Vitamin deficiencies Signup and view all the answers

Which physiological response results when a cell encounters pathological stimuli and reaches its adaptive limits?

Cell injury Signup and view all the answers

What distinguishes ischemia from hypoxia?

Ischemia involves an inadequate blood supply, not directly oxygen. Signup and view all the answers

What is the first effect of hypoxia on cellular respiration?

Reduced intracellular ATP Signup and view all the answers

Which enzyme stimulates increased rates of anaerobic glycolysis when ATP and AMP levels decrease?

Phosphofructokinase Signup and view all the answers

What occurs with the accumulation of extracellular calcium during ischemic injury?

Activation of ATPases Signup and view all the answers

What is NOT a sign of irreversible cellular injury?

Enhanced protein synthesis Signup and view all the answers

What is a consequence of the continued loss of membrane phospholipids during irreversible injury?

Detachment of the cell membrane Signup and view all the answers

What happens when hypoxia leads to acute cellular swelling?

Accumulation of lactic acid Signup and view all the answers

What mediates cell death following the generation of oxygen free radicals?

Activation of phospholipases Signup and view all the answers

What role do toxic oxygen radicals play during reperfusion injury?

They activate proteolytic enzymes Signup and view all the answers

What is the primary cause of cytoplasmic eosinophilia?

Cytoplasmic acidosis and loss of ribosomes Signup and view all the answers

Which type of necrosis is characterized by the preservation of structural outlines of the coagulated cells or tissue?

Coagulative necrosis Signup and view all the answers

Which cellular change is associated with karyorrhexis?

Fragmentation of the pyknotic nucleus Signup and view all the answers

In which type of necrosis is the central necrotic area described as having a cheesy, white gross appearance?

Caseous necrosis Signup and view all the answers

Which ultrastructural change indicates damage to the mitochondria?

Swelling and phospholipid-rich amorphous densities Signup and view all the answers

What is the primary mechanism of autolysis during necrosis?

Enzymatic digestion of the cells from within themselves Signup and view all the answers

What process primarily leads to liquefactive necrosis?

Infection leading to white cell accumulation Signup and view all the answers

Which of the following accurately describes gangrenous necrosis?

Coagulative necrosis with superimposed liquefactive necrosis Signup and view all the answers

What is the consequence of fat necrosis following acute pancreatitis?

Destruction of fat due to pancreatic enzymes Signup and view all the answers

What is a key characteristic of apoptosis observed in stained sections?

Clusters of cells with intensely eosinophilic cytoplasm Signup and view all the answers

Which of the following can initiate apoptosis?

Radiation and toxins Signup and view all the answers

What type of intracellular accumulation results from a genetic enzymatic defect?

Storage diseases Signup and view all the answers

How does apoptosis differ from necrosis in terms of its cellular response?

Apoptosis does not elicit an inflammatory response Signup and view all the answers

What is a consequence of intracellular accumulation of harmful substances?

Decreased cellular function Signup and view all the answers

Which process is NOT associated with apoptosis?

Tissue enlargement due to inflammation Signup and view all the answers

Which of these describes an abnormal endogenous substance accumulation?

Excessive fat in liver due to inadequate metabolism Signup and view all the answers

What is dystrophic calcification characterized by?

Calcium deposition in dead or dying tissues Signup and view all the answers

In which condition might metastatic calcification occur?

Primary endocrine dysfunction Signup and view all the answers

Which option does NOT typically cause hypercalcemia?

Hormonal regulation Signup and view all the answers

What happens to cells during atrophy?

Cells shrink by loss of cell substance Signup and view all the answers

What is a common cause of atrophy?

Decreased workload Signup and view all the answers

How does hypertrophy primarily occur?

Increased synthesis of structural proteins Signup and view all the answers

Which of the following is NOT a characteristic of dystrophic calcification?

Accompanied by metabolic derangement Signup and view all the answers

Where is metastatic calcification most likely to occur?

In interstitial tissues Signup and view all the answers

What is the most common organ affected by fatty change (steatosis)?

Liver Signup and view all the answers

Which type of accumulation results in xanthomas?

Cholesterol and cholesterol esters Signup and view all the answers

What common cause of fatty change could impair the liver's ability to synthesize apoproteins?

Alcohol hepatotoxins Signup and view all the answers

Under the light microscope, how does fatty change present in parenchymal cells?

Vacuoles coalescing to clear spaces Signup and view all the answers

What is pathologic calcification characterized by?

Abnormal accumulation of calcium salts Signup and view all the answers

What leads to the formation of foamy cells in atherosclerosis?

Lipid debris in macrophages Signup and view all the answers

What pigment accumulates in the epidermis to cause freckles?

Melanin Signup and view all the answers

Which of the following conditions is most likely to result in an abnormal accumulation of glycogen?

Diabetes mellitus Signup and view all the answers

What is the primary process responsible for the disaggregation of granular elements in necrotic cells?

Hydrolytic enzyme digestion Signup and view all the answers

Which type of necrosis is primarily associated with anoxic cell death in all tissues except the brain?

Coagulative necrosis Signup and view all the answers

What histological feature is specifically associated with karyolysis during necrosis?

Digestion of DNA Signup and view all the answers

What change occurs in the mitochondria as a result of cellular injury?

Diminished ATP production Signup and view all the answers

Which of the following best describes gangrenous necrosis?

Ischemic coagulative necrosis with superimposed infection Signup and view all the answers

In which type of necrosis would you expect to see a 'cheesy' gross appearance of the necrotic area?

Caseous necrosis Signup and view all the answers

What type of cellular change is associated with cytoplasmic eosinophilia during necrosis?

Loss of ribosomes Signup and view all the answers

What is a common outcome of liquefactive necrosis?

Formation of pus and fluid accumulation Signup and view all the answers

What is the consequence of decreased ATP levels during hypoxia?

Increased intracellular calcium Signup and view all the answers

Which enzyme is stimulated due to decreased levels of ATP and AMP in hypoxic conditions?

Phosphofructokinase Signup and view all the answers

What is an early irreversible change observed in cells after persistent hypoxia?

Vacuolization of mitochondria Signup and view all the answers

What role do oxygen free radicals play in cell injury?

They are mediators of cell death. Signup and view all the answers

Which of the following is NOT associated with irreversible injury?

Accumulation of lactic acid Signup and view all the answers

What happens to ribosomes during early stages of hypoxic injury?

They detach from the rough endoplasmic reticulum. Signup and view all the answers

What characterizes the formation of myelin figures in dead cells?

Replacement by whorled masses of phospholipids. Signup and view all the answers

Which cellular component is damaged by toxic oxygen radicals during reperfusion injury?

Cell membrane phospholipids Signup and view all the answers

What does fat necrosis specifically describe?

Focal areas of fat destruction from pancreatic enzyme release Signup and view all the answers

Which of the following best describes the appearance of apoptotic cells under H&E staining?

Round masses with eosinophilic cytoplasm and condensed nuclear chromatin Signup and view all the answers

What is the primary initiator of apoptosis?

Engagement of specific cell receptors Signup and view all the answers

Which type of intracellular accumulation is characterized by an inadequate metabolism rate of a normal substance?

Fatty change of the liver Signup and view all the answers

What event primarily occurs during the process of apoptosis?

Formation of apoptotic bodies Signup and view all the answers

Which of the following is NOT a form of stimuli that can initiate apoptosis?

Engagement of anti-apoptotic receptors Signup and view all the answers

How is apoptosis generally characterized in terms of inflammation?

It occurs without triggering an inflammatory response. Signup and view all the answers

Which process contributes to the formation of apoptotic bodies during apoptosis?

Activation of endonucleases Signup and view all the answers

What underlying condition may lead to hypercalcemia due to increased parathyroid hormone levels?

Hyperparathyroidism Signup and view all the answers

In which scenario would dystrophic calcification most likely occur?

In areas of necrosis with normal calcium levels Signup and view all the answers

What is the primary difference between atrophy and hypertrophy?

Atrophy is the shrinking of cells; hypertrophy is the enlargement of cells. Signup and view all the answers

Which of the following describes a common result of cellular hypertrophy?

Increased synthesis of structural proteins Signup and view all the answers

What may induce both apoptosis and atrophy in cells?

Loss of hormonal stimulation Signup and view all the answers

What condition is most likely to cause metastatic calcification?

Hyperparathyroidism Signup and view all the answers

How are intracellular and extracellular calcifications generally characterized?

Intracellular calcifications are generally basophilic deposits; extracellular calcifications often form bone. Signup and view all the answers

What is the primary regulatory factor of cellular adaptations in response to stress?

Hormonal stimulation Signup and view all the answers

Study Notes

### Necrosis vs. Apoptosis

Necrosis: Characterized by cell swelling, membrane rupture, and inflammation, uncontrolled cell demise.
Apoptosis: Programmed cell death, characterized by cell shrinkage, nuclear fragmentation, and formation of apoptotic bodies, without inflammation.

Hypoxia and Cell Injury

Hypoxia: (low oxygen) can cause cell injury by affecting various cellular processes like ATP production, and causing membrane damage
Conditions causing hypoxia: Cardiac arrest, severe anemia, respiratory failure, severe blood loss, and circulatory shock.

Factors Influencing Cell Injury

Type of cell and its health status: Influences the severity and nature of cell injury due to differences in metabolic rates, enzyme levels, and reserve capacity.

Intracellular Systems Vulnerable to Injury

Vulnerable: Cell membranes, mitochondria, DNA, and ribosomes.
Not vulnerable: Cellular nuclei (nucleus can have damage but is not the initial target)

Calcium Transporters in Cellular Injury

Calcium Transporters: Regulate intracellular calcium levels, playing a crucial role in cell survival and death.
Role: Dysfunction during injury leads to increased intracellular calcium, causing activation of enzymes which damage cellular components.

Nutritional Imbalances and Cell Injury

Common Cause: Prolonged malnutrition, vitamin deficiency, and alcohol abuse, can lead to nutritional deficiencies and oxidative stress.

Adaptive Limits and Cell Injury

Adaptive Limits: When a cell encounters pathological stimuli exceeding its adaptive capacity, triggers cell injury or death.
Result: Adaptive mechanisms like hypertrophy, hyperplasia, and atrophy can be overwhelmed leading to cell injury.

### Ischemia vs. Hypoxia

Ischemia: Reduced blood flow to tissues, meaning reduced oxygen and nutrients, and accumulation of metabolic waste products
Hypoxia: Low oxygen tension in tissues.

Hypoxia and Cellular Respiration

First effect: Decreased ATP production, impacting energy-dependent cellular functions.

Enzyme Activation in Hypoxia

Enzyme: Phosphofructokinase, which stimulates increased rates of anaerobic glycolysis. This helps compensate for decreased ATP production, but leads to lactic acid build-up.

Extracellular Calcium Accumulation

Ischemic Injury: Accumulation of extracellular calcium in the injured tissue, contributes to cell death by triggering the release of harmful enzymes (e.g., phospholipases).

Irreversible Cellular Injury

Sign: Cellular swelling, nuclear fragmentation, and mitochondrial damage, are signs of irreversible injury.
Not a sign: Initially decreased ATP, an early sign of reversible injury.

### Membrane Phospholipid Loss

Consequence: Loss of membrane integrity, leading to leakage of intracellular contents, further contributing to cell death.

Hypoxia and Cellular Swelling

Hypoxia: Leads to acute cellular swelling due to impaired ion pumps, causing a buildup of intracellular fluid.

### Oxygen Free Radicals and Cell Death

Mediation: Oxygen free radicals (ROS) contribute to cell death by causing oxidative damage to lipids, proteins, and DNA.

Toxic Oxygen Radicals in Reperfusion Injury

Role: Toxic oxygen radicals are generated during reperfusion injury, further exacerbating tissue damage due to oxidative stress.

Cytoplasmic Eosinophilia

Cause: Increased eosinophilia (pink staining) of the cytoplasm in necrotic cells is due to the loss of cytoplasmic RNA and increased binding of eosin stain to denatured proteins.

Coagulative Necrosis

Characteristic: Preservation of the structural outlines of the coagulated cells or tissues.
Example: Most commonly seen in tissues with abundant protein, like the heart, kidney, and liver.

Karyorrhexis

Association: Karyorrhexis (nuclear fragmentation) is associated with chromatin clumping and nuclear fragmentation, signifying irreversible cell damage.

Caseous Necrosis

Description: Central necrotic area with a cheesy, white gross appearance.
Example: Tuberculosis infection.

### Mitochondrial Damage

Ultrastructural change: Mitochondrial swelling, rupture, and formation of vacuoles.

Autolysis in Necrosis

Mechanism: Autolysis is a process of self-digestion, where lysosomal enzymes released from dying cells break down the cellular components leading to necrosis.

### Liquefactive Necrosis

Process: Process where dead cells get dissolved and liquefied by enzymatic activity.
Example: Occurs in the brain due to the abundance of lysosomes, and also in abscesses (where the contents are liquefied).

### Gangrenous Necrosis

Description: A form of necrosis caused by ischemia, typically affecting extremities.
Types: Dry gangrene occurs in the presence of good blood supply, whereas wet gangrene occurs with poor blood supply.
Characteristics: Dry gangrene is characterized by shrunken tissues with dark brown discoloration, while wet gangrene is characterized by swollen tissues with a foul odor.

### Fat Necrosis

Consequence: Fat necrosis following acute pancreatitis is characterized by pancreatic lipase-mediated breakdown of triglycerides, leading to saponification (formation of soap-like substances).

### Apoptosis in Stained Sections

Characteristic: Cell shrinkage, nuclear fragmentation, and formation of apoptotic bodies which appear as small, round, membrane-bounded fragments

### Initiators of Apoptosis

Initiators: These triggers include, DNA damage, cellular stress, withdrawal of growth factors, and activation of death receptors.

### Intracellular Accumulation Due to Genetic Defect

Result: Lysosomal storage disease due to inherited genetic defects affecting lysosomal enzymes, leading to accumulation of undigested substances.

### Apoptosis vs. Necrosis

Apoptosis: Programmed cell death that is energy dependent, involves activation of specific caspases, and does not cause inflammation.
Necrosis: Uncontrolled cell death associated with cell injury caused by external factors like trauma, toxins, or ischemia, causing inflammation.

### Consequence of Harmful Substance Accumulation

Consequence: Cellular toxicity, dysfunction, and even cell death depending on the nature and amount of the substance.

### Process Not Associated with Apoptosis

Process: Inflammation. Apoptosis is a silent process with no inflammation associated with it.

### Abnormal Endogenous Substance Accumulation

Example: Accumulation of glycogen in various tissues like the liver and muscle in patients with glycogen storage diseases.
Cause: Due to a defect in enzymes involved in glycogen metabolism.

### Dystrophic Calcification

Characterized: Localized deposition of calcium salts, primarily in areas of previous tissue injury or necrosis where there is damaged tissue and tissue degradation.

### Metastatic Calcification

Condition: Hypercalcemia (high levels of calcium in the blood)
Description: Abnormal calcium deposition in normal tissues, often seen in tissues with high phosphate levels, such as the kidneys, lungs, and blood vessels.

### Hypercalcemia

Causes: Primary hyperparathyroidism, malignancy, excessive intake of vitamin D, and immobilization.
Not a cause: Renal failure is associated with hypocalcemia, not hypercalcemia.

Atrophy in Cells

Cellular change: Decrease in cell size due to a reduction in organelles.

### Common Cause of Atrophy

Cause: Decreased workload, malnutrition, diminished blood supply, and hormonal stimulation.

### Mechanism of Hypertrophy

Primarily occurs: Due to increased production of cellular proteins and organelles, leading to larger cell sizes and a greater functional capacity.

### Characteristics of Dystrophic Calcification

Characteristic: It is not associated with hypercalcemia.
Location: It occurs in dying or dead tissues, where the tissues undergo necrosis and calcification.

### Metastatic Calcification Location

Most likely location: Kidney, lungs, and blood vessels, due to their high phosphate levels and ability to excrete calcium.

### Fatty Change

Most common organ: The liver, due to its central role in lipid metabolism.

### Xanthomas

Result: Lipid accumulation in macrophages, forming characteristic tumor-like deposits in the skin.

### Impaired Liver Function and Fatty Change

Impairment: Fatty change can be caused by impairment in the synthesis of apoproteins, crucial components for the transport of lipids, leading to their accumulation in the liver.

### Fatty Change Histology

Parenchymal cells: Fatty change is evident under a light microscope, appearing as small vacuoles or large globules in the cytoplasm of parenchymal cells.

### Pathologic Calcification

Characterized: Abnormal calcification, either dystrophic (in dead or injured tissues) or metastatic (in normal tissues with high blood calcium levels).

### Formation of Foamy Cells

Process: Accumulation of cholesterol and cholesterol esters within macrophages, giving them a foamy appearance, contributing to atherosclerosis plaque formation.

### Freckles and Pigment Accumulation

Pigment: Melanin, accumulating in the epidermis, leads to freckles, which are focal areas of increased melanin pigmentation.

### Abnormal Glycogen Accumulation

Condition: Glycogen storage diseases, genetic disorders affecting enzymes involved in glycogen metabolism, leading to excessive glycogen accumulation in various tissues.

### Disaggregation of Granular Elements

Primary process: Cell injury, causing the disintegration of cellular components.

### Anoxic Cell Death

Necrosis type: Coagulative necrosis, occurring in most tissues except the brain.

### Karyolysis

Histological feature: Nuclear fading, a characteristic of karyolysis, where genetic material is degraded by DNAases.

### Mitochondrial Damage

Change: Cellular injury, especially hypoxia, causes swelling, rupture, and the formation of vacuoles, which disrupt the functions of mitochondria.

### Gangrenous Necrosis Description

Description: A form of necrosis resulting from ischemia, particularly affecting extremities, affecting tissue due to lack of blood flow.

### Caseous Necrosis Appearance

Appearance: Cheesy, white gross appearance of the necrotic area, commonly seen in tissues affected by tuberculosis.

### Cytoplasmic Eosinophilia in Necrosis

Association: The accumulation of eosinophilic (pink-staining) proteins due to loss of cytoplasmic RNA and protein denaturation.

### Liquefactive Necrosis Consequence

Consequence: Liquefied debris and pus formation, often seen in the brain, bacterial infections, and abscesses.

### Decreased ATP Levels in Hypoxia

Consequence: Leads to impaired cellular functions, including membrane ion pumps, causing cell swelling and eventual cell death.

### Enzyme Stimulation in Hypoxic Conditions

Enzyme: Phosphofructokinase, stimulated due to decreased ATP and AMP levels, increases anaerobic glycolysis to compensate for reduced ATP production.

### Early Irreversible Change

Change: Irreversible cell damage, characterized by extensive mitochondrial swelling, disruption of cell membranes, and cell death.

### Role of Oxygen Free Radicals

Role: They contribute to damaging cell membranes, proteins, and DNA, leading to cell injury.

### Irreversible Injury

Not associated: Decreased ATP levels, an early sign of reversible cell injury.

### Ribosomes in Hypoxic Injury

Change: Detach from the endoplasmic reticulum, impairing protein synthesis, contributing to cell malfunction.

### Myelin Figures

Formation: Derived from degraded cell membranes during cell injury.
Appearance: Layered, concentric, whorled structures, often visible under microscopy.

### Cell Component Damaged by Toxic Oxygen Radicals

Component: Cell membranes, particularly the phospholipid bilayer, are vulnerable to oxidative stress caused by toxic oxygen radicals.

### Fat Necrosis Description

Description: Refers to the destruction of adipose tissue, typically occurring in the pancreas, caused by the release of pancreatic lipase, which breaks down fat into fatty acids and glycerol.

### Apoptotic Cells Under Microscopy

Appearance: Apoptotic cells shrink and display nuclear fragmentation, forming small, round, membrane-bound bodies, known as apoptotic bodies.

### Primary Initiator of Apoptosis

Initiator: The activation of caspases, a family of cysteine proteases, plays a crucial role in triggering the cascade of events leading to apoptosis.

### Intracellular Accumulation Due to Inadequate Metabolism

Type: Lysosomal storage diseases, a group of genetic disorders resulting from deficient enzymes involved in the breakdown of various molecules.
Example: Accumulation of glycogen in glycogen storage diseases or accumulation of lipids in lipid storage diseases.

### Event During Apoptosis

Event: Nuclear fragmentation, involving the breakdown of DNA by endonucleases.

### Stimuli that can Initiate Apoptosis

Stimuli: Growth factor deprivation, DNA damage, exposure to cytotoxic T cells, and activation of death receptors.
Not a Stimuli: Increased intracellular sodium levels is not a typical initiator of apoptosis.

### Apoptosis and Inflammation

Characteristic: Apoptosis is generally characterized by being anti-inflammatory.

### Apoptotic Bodies Formation

Process: Cells undergoing apoptosis fragment into small membrane-enclosed bodies, known as apoptotic bodies, containing cellular components.

### Hypercalcemia Cause

Cause: Increased parathyroid hormone (PTH) levels can lead to hypercalcemia due to increased bone resorption and reduced calcium excretion by the kidneys.

### Dystrophic Calcification Scenario

Scenario: Damaged or dead tissues, such as areas of necrosis, atherosclerotic plaques, and old hematomas.

### Atrophy vs. Hypertrophy

Difference: Atrophy is a decrease in cell size, while hypertrophy is an increase in cell size.

### Cellular Hypertrophy Result

Result: Increased functional capacity of the affected tissue or organ.

### Inducer of Apoptosis and Atrophy

Inducer: Cellular stress, including inadequate nutrition, prolonged hypoxia, and toxic substances can trigger both apoptosis and atrophy in cells.

### Metastatic Calcification Cause

Cause: Hypercalcemia, due to high calcium levels in the blood.

### Intracellular and Extracellular Calcifications

Characterized: Intracellular calcification occurs within the cytoplasm of cells, while extracellular calcification occurs in the extracellular matrix or in tissues.

### Cellular Adaptations to Stress

Primary regulatory factor: The cellular environment, specifically the presence of growth factors, hormones, and other external stimuli, play a crucial role in regulating cellular adaptations.

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Description

This quiz explores the concepts of cell injury, including the differences between necrosis and apoptosis. It covers various causes of cell injury such as hypoxia, physical agents, chemicals, and genetic defects. Test your understanding of how these factors contribute to cellular changes and ultimately cell death.