Cell Injury and Its Causes

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Questions and Answers

What characterizes dystrophic calcification?

Always causes significant organ impairment.

Is primarily related to increased calcium levels in the blood.

Is associated with normal serum levels of calcium. (correct)

Occurs in living tissues affected by metabolic derangement.

Which of the following conditions can lead to hypercalcæmia?

Chronic dehydration.

Hypoparathyroidism.

Chronic liver disease.

Primary hyperparathyroidism. (correct)

What is the primary difference between atrophy and hypertrophy?

Atrophy leads to an increase in cell size, while hypertrophy decreases it.

Hypertrophy is a response to decreased workload, while atrophy occurs during increased function.

Atrophy involves shrinkage in cell size, whereas hypertrophy involves an increase in cell size. (correct)

Both atrophy and hypertrophy result in the same cellular function.

In metastatic calcification, which statement is correct?

It can occur in normal tissues during hypercalcæmia. Signup and view all the answers

What is a common cause of atrophy in cells?

Decreased blood supply. Signup and view all the answers

What is a key characteristic of necrosis?

Cell swelling and organellar breakdown Signup and view all the answers

Which of the following best distinguishes hypoxia from ischemia?

Ischemia results in hypoxic cell injury Signup and view all the answers

Which intracellular system is particularly vulnerable to injury?

Cell membrane integrity Signup and view all the answers

How does aging contribute to cell injury?

Through physiological changes affecting adaptability Signup and view all the answers

What type of injury involves adaptive capability being exceeded?

Cell death Signup and view all the answers

Which of the following is a physical agent that can cause cell injury?

Extreme temperatures Signup and view all the answers

What role do chemicals and drugs play in cell injury?

They can alter membrane permeability Signup and view all the answers

Which aspect does not contribute to the severity of cell injury?

External environmental conditions Signup and view all the answers

What does cytoplasmic eosinophilia indicate?

Cytoplasmic acidosis Signup and view all the answers

What type of necrosis is characterized by preservation of cellular outlines for days?

Coagulative necrosis Signup and view all the answers

Which of the following is a morphological change seen in necrosis?

Karyolysis due to digestion of DNA Signup and view all the answers

Which type of necrosis is commonly associated with tuberculosis?

Caseous necrosis Signup and view all the answers

What cellular change leads to a glassy appearance in necrotic cells?

Loss of glycogen Signup and view all the answers

Which process is responsible for the enzymatic digestion in necrosis?

Autolysis Signup and view all the answers

What is a key feature of liquefactive necrosis?

Transformation into a viscous liquid Signup and view all the answers

Which of the following is NOT a nuclear alteration observed in necrosis?

Cell hypertrophy Signup and view all the answers

Which factor is NOT associated with fatty change in tissues?

Increased glycolysis Signup and view all the answers

What distinguishes gangrenous necrosis from other types of necrosis?

It involves ischæmic coagulative necrosis with infection. Signup and view all the answers

What is the initial effect of hypoxia on cellular respiration?

Reduction of aerobic respiration Signup and view all the answers

What results from the influx of extracellular calcium during ischæmic injury?

Activation of cellular enzymes Signup and view all the answers

Which of the following is a characteristic of irreversible injury?

Extensive plasma membrane damage Signup and view all the answers

What is the role of mitochondrial calcium release during cellular injury?

To activate proteases Signup and view all the answers

What occurs as a result of the accumulation of lactic acid during hypoxia?

Decreased intracellular pH Signup and view all the answers

What happens during reperfusion of an ischæmic area?

Calcium-mediated injury Signup and view all the answers

Which process occurs when ribosomes detach from the rough endoplasmic reticulum during hypoxia?

Reduced protein synthesis Signup and view all the answers

What is indicated by cytoplasmic eosinophilia under light microscopy?

Accumulation of lactic acid and inorganic phosphates Signup and view all the answers

Which factor contributes to cell death during ischæmic injury?

Formation of myelin figures Signup and view all the answers

What is the primary result of decreased ATP and AMP levels during cellular injury?

Increased rate of anaerobic glycolysis Signup and view all the answers

What is the primary trigger for apoptosis in cells?

Injury by radiation and toxins Signup and view all the answers

What characterizes fat necrosis in the context of acute pancreatitis?

Focal areas of fat destruction Signup and view all the answers

Which of the following statements about apoptosis is incorrect?

Apoptosis can lead to inflammation Signup and view all the answers

Which of the following can occur due to intracellular accumulation?

Temporary storage of normal substances Signup and view all the answers

What is the consequence of protease activation during apoptosis?

Formation of apoptotic bodies Signup and view all the answers

Which type of apoptosis is responsible for cell deletion in the thymus?

Deletion of autoreactive T cells Signup and view all the answers

What appearance do apoptotic cells typically have under H&E staining?

Intensely eosinophilic cytoplasm Signup and view all the answers

Which of the following describes a characteristic of storage diseases?

Faulty metabolism of certain substances due to enzymatic defects Signup and view all the answers

What happens during karyorrhexis in apoptosis?

Nuclear chromatin condenses and aggregates Signup and view all the answers

What might cause intracellular accumulation in normal cells?

Increased production of substances Signup and view all the answers

Study Notes

Cell Injury

Cells maintain a narrow range of physiological activities within their intracellular milieu
Cell injury occurs when the adaptive capability of a cell is exceeded
There are two principal patterns of cell death: necrosis and apoptosis
Necrosis occurs after exposure to noxious conditions and is characterized by cell swelling, protein denaturation and organellar breakdown
Apoptosis is programmed cell death occurring in normal or physiological conditions

Causes Of Cell Injury

Hypoxia: Impedes aerobic oxidative respiration; should be distinguished from ischemia, which also results in hypoxic cell injury
Physical agents: Trauma, temperature extremes, radiation, electric shock, sudden atmospheric pressure changes
Chemicals and drugs: May alter membrane permeability, osmotic homeostasis, or enzyme cofactor integrity
Microbiologic agents: Range from viruses to tapeworms
Immunologic reactions: Body's immune system can cause cell injury, e.g., anaphylactic reaction
Genetic defects: E.g., Down syndrome, sickle cell anemia
Nutritional imbalances: Protein-calorie insufficiency, vitamin deficiencies; diets rich in animal fat are implicated in atherosclerosis pathogenesis
Aging:

Mechanisms Of Cell Injury

Cell response to injuries depends on the type of injury, duration, and severity
Consequences of injury depend on the type of cell, current health status, and adaptability
Four intracellular systems are vulnerable to injury:
- Cell membrane integrity (altering ionic and osmotic homeostasis)
- Aerobic respiration
- Protein synthesis
- Genetic apparatus
Calcium influx:
- Cytosolic free calcium is maintained at low levels by ATP-dependent calcium transporters
- Ischemia or toxins allow calcium influx from the extracellular space, with mitochondrial calcium release
- Activates enzymes like phospholipases, proteases, ATPases, and endonucleases
Oxygen free radicals: Important mediators of cell death

Ischemic And Hypoxic Injury

Reversible Injury:
- First effect of hypoxia is on aerobic respiration, reducing intracellular ATP
- Reduced ATP leads to:
  - Influx of extracellular calcium
  - Reduced plasma membrane sodium pump activity
  - Intracellular sodium accumulation
  - Potassium diffusion out of the cell
  - Isosmotic water gain, resulting in acute cellular swelling
- Accumulation of metabolites: inorganic phosphates, lactic acid, purine nucleotides
- Increased anaerobic glycolysis due to decreased ATP and AMP, leading to glycogen depletion, lactic acid and inorganic phosphate accumulation, and reduced intracellular pH
- Detachment of ribosomes from the endoplasmic reticulum, reducing protein synthesis
- If hypoxia continues, the cytoskeleton disappears, resulting in loss of ultrastructural features (microvilli) and cell surface blebs
Irreversible Injury:
- Severe vacuolization of mitochondria and calcium particle accumulation
- Extensive plasma membrane damage
- Swelling of lysosomes
- Calcium-mediated injury upon reperfusion of oxygen
- Continued loss of proteins, coenzymes, and RNA from hyperpermeable membranes
- Leakage of lysosomal enzymes into the cytoplasm, degrading cytoplasmic components
- Dead cells may be replaced by whorled masses of phospholipids (myelin figures)

Mechanisms Of Irreversible Injury

Progressive loss of membrane phospholipids
Cytoskeletal abnormalities: Protease activation and increased calcium can detach the cell membrane
Toxic oxygen radicals: Generated after reperfusion of the ischemic area, released by neutrophils
Lipid breakdown products: Have detergent effects

Cellular Accumulations

Cells may accumulate abnormal substances transiently or permanently, harmful or injurious, located in the cytoplasm or nucleus
Substances may be synthesized by the cell or produced elsewhere
Accumulations categorized into three types:
- Normal endogenous substance produced at normal or increased rate, with inadequate metabolism (e.g., fatty change of the liver)
- Normal or abnormal endogenous substance that can't be metabolized due to genetic enzymatic defect (storage diseases)
- Deposition in dead or dying tissues (dystrophic calcification)

Dystrophic Calcification

Deposition occurs despite normal serum calcium levels and absence of calcium metabolic derangement
Encountered in areas of necrosis, seen in atheromas of advanced atherosclerosis, intimal injuries of large arteries, aging, aortic valves
Appears as intracellular or extracellular basophilic deposits; sometimes heterotopic bone may be formed

Metastatic Calcification

Occurs in normal tissues when hypercalcemia exists
Causes of hypercalcemia include:
- Primary endocrine dysfunction (hyperparathyroidism)
- Tumors associated with increased bone catabolism (multiple myeloma, metastatic cancer, leukemia)
- Ingested exogenous substances causing vitamin D intoxication or milk alkali syndrome
- Sarcoidosis
- Advanced renal failure (secondary hyperparathyroidism due to phosphate retention)
Metastatic calcification may occur widely in tissues, primarily in the interstitial tissues, kidneys, lungs, and gastric mucosa
Usually does not significantly impair organ function, but extensive nephrocalcinosis can cause impairment

Cellular Adaptations Of Growth And Differentiation

Physiologic adaptations are responses to normal stimulation by hormones or endogenous chemicals (e.g., breast growth and lactation)
Pathologic adaptations often share the same underlying mechanisms, allowing cells to modulate their environment and avoid injury

Atrophy

Shrinkage in cell size due to loss of cell substance; may involve the entire organ
Atrophied cells have diminished function but are not dead
Apoptotic death can be induced by the same signals causing atrophy
Causes:
- Decreased workload
- Loss of innervation
- Diminished blood supply
- Inadequate nutrition
- Loss of endocrine stimulation
- Aging
Cells become smaller, reaching an equilibrium with reduced blood supply, nutrition, or trophic stimulation
Biochemically: Decreased synthesis, increased catabolism, or both

Hypertrophy

Increase in cell size due to increased synthesis of structural proteins and organelles, resulting in an enlarged organ
Examples:
- Increased muscle mass due to exercise (physiological hypertrophy)
- Enlargement of the heart in hypertension (pathological hypertrophy)

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Description

This quiz explores the concepts of cell injury, including the mechanisms behind necrosis and apoptosis. Additionally, it covers various causes of cell injury such as hypoxia, physical agents, chemicals, and immunologic reactions. Test your understanding of cellular responses to harmful conditions.