Cell Injury and Types of Cell Death

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Questions and Answers

What characterizes necrosis in cells?

Cell swelling and protein denaturation (correct)

Programmed cell death

Apoptosis and cellular adaptation

Reduction in organelle size

Which of the following is primarily caused by inadequate oxygenation of the blood?

Aging

Nutritional imbalances

Hypoxia (correct)

Genetic defects

Which intracellular system is NOT vulnerable to injury?

Aerobic respiration

Cell membrane integrity

Protein synthesis

Hormonal response (correct)

Which of the following results from a physiological response to stress or stimulus?

Apoptosis Signup and view all the answers

What can lead to the release of mitochondrial calcium, promoting further cell injury?

Influx of extracellular calcium during ischemia Signup and view all the answers

Which of these is NOT a cause of cell injury?

Social influences Signup and view all the answers

Which of the following mechanisms is responsible for maintaining low cytosolic free calcium levels?

Calcium transporters Signup and view all the answers

What type of cell injury is caused by anaphylactic reactions?

Immunologic reactions Signup and view all the answers

Which condition is primarily associated with hypercalcemia?

Hyperparathyroidism Signup and view all the answers

What is the primary cause of metastatic calcification?

Hypercalcemia Signup and view all the answers

Which cellular adaptation is characterized by an increase in cell size?

Hypertrophy Signup and view all the answers

What triggers compensatory hyperplasia?

Removal or disease of part of the tissue Signup and view all the answers

Which adaptation involves the replacement of one adult cell type with another?

Metaplasia Signup and view all the answers

Which statement about atrophy is correct?

Atrophy results in the shrinkage of cells. Signup and view all the answers

What is a common cause of hyperplasia?

Excessive hormonal or growth factor stimulation Signup and view all the answers

Which tissue is most commonly affected by metastatic calcification?

Interstitial tissues Signup and view all the answers

What is the primary characteristic of coagulative necrosis?

Acidophilic coagulated anucleated cells Signup and view all the answers

Which type of necrosis is commonly associated with tuberculous infections?

Caseous necrosis Signup and view all the answers

What defines liquefactive necrosis?

Focal bacterial or fungal infection with white cell accumulation Signup and view all the answers

Which of the following correctly describes fat necrosis?

Associated with acute pancreatitis and triglyceride hydrolysis Signup and view all the answers

What initiates the process of apoptosis?

Engagement of specific receptors and withdrawal of growth factors Signup and view all the answers

In which situation would intracellular accumulation of normal endogenous substances occur?

With increased rate of synthesis and inadequate metabolism Signup and view all the answers

Which of the following best describes the morphology of apoptotic cells?

Cells with fragmented nuclei and eosinophilic cytoplasm Signup and view all the answers

Which type of necrosis is often seen with ischaemic conditions and can involve superimposed infections?

Gangrenous necrosis Signup and view all the answers

What is the primary consequence of decreased ATP levels during hypoxic injury?

Increased extracellular sodium levels Signup and view all the answers

Cholesterol accumulation in macrophages is most notably associated with which condition?

Atherosclerosis Signup and view all the answers

What is dystrophic calcification?

Calcium deposition in dead or dying tissues regardless of serum calcium levels Signup and view all the answers

What is a common feature of reversible cell injury observed under a light microscope?

Clear vacuoles in the cytoplasm Signup and view all the answers

Which of the following is NOT a mechanism of irreversible cell injury?

Dissociation of polysomes from the ribosomes Signup and view all the answers

Which condition is least likely to lead to fatty change in the liver?

Dehydration Signup and view all the answers

How do free radicals primarily cause cellular damage?

By reacting with lipids, DNA, and proteins Signup and view all the answers

What occurs during the process of apoptosis?

Formation of apoptotic bodies that are phagocytized Signup and view all the answers

What effect does reperfusion have on previously ischemic tissue?

It can lead to calcium-mediated injury. Signup and view all the answers

Which pigment accumulation is caused by local or systemic excess iron?

Hemosiderin Signup and view all the answers

Fatty change in tissues primarily involves which substance?

Triglycerides Signup and view all the answers

Which type of necrosis maintains the structural outline of the tissue for some time?

Coagulative necrosis Signup and view all the answers

In chemical injury, how do certain chemicals induce toxicity?

By converting into reactive toxic metabolites within the body Signup and view all the answers

Which of the following leads to cytoplasmic eosinophilia in reversible cell injury?

Cytoplasmic acidosis Signup and view all the answers

What is one of the key roles of the decrease in ATP levels during hypoxic conditions?

Stimulation of anaerobic glycolysis Signup and view all the answers

What is a key characteristic of free radicals that contributes to their reactivity?

Presence of a single unpaired electron Signup and view all the answers

Which of the following mechanisms underlies the toxic effects of oxygen free radicals?

Oxidation of lipids and proteins Signup and view all the answers

During ischemic injury, what is the initial effect of hypoxia on mitochondrial function?

Decreased oxidative phosphorylation Signup and view all the answers

What is a consequence of sustained hypoxia on the cytoskeleton?

Disappearance of structural features Signup and view all the answers

What is a notable feature of necrosis following irreversible injury?

Loss of membrane integrity Signup and view all the answers

Study Notes

### Cell Injury

Cells strive to maintain a stable internal environment, but can adapt to stress to keep functioning.
If stress exceeds adaptive capabilities, cell injury develops.
There are two main types of cell death:
- Necrosis: Occurs due to noxious conditions, causing cell swelling, protein denaturation, and organelle breakdown.
- Apoptosis: Programmed cell death, often occurring under normal or physiologic conditions.

Causes of Cell Injury

Hypoxia: Inadequate oxygenation of the blood, inhibiting aerobic respiration.
- It differs from ischemia, which is reduced blood flow, also resulting in hypoxic injury.
Physical Agents: Trauma, extreme temperatures, radiation, electric shock, and sudden atmospheric pressure changes.
Chemicals and Drugs: Can alter membrane permeability, osmotic balance, or enzyme activity, leading to damage.
Microbiologic Agents: Viruses, bacteria, parasites, and fungi can cause cell injury.
Immunologic Reactions: Immune responses can cause cell injury, such as in anaphylaxis.
Genetic Defects: Examples include Down's syndrome and sickle cell anemia.
Nutritional Imbalances: Protein-calorie deficiency, vitamin deficiencies, and high animal fat diets can contribute to cell damage.
Aging: The aging process itself can lead to cellular damage.

Mechanisms of Cell Injury

Four major intracellular systems susceptible to injury:
- Cell membrane integrity, crucial for maintaining ionic and osmotic balance.
- Aerobic respiration, essential for ATP production.
- Protein synthesis, for building and repairing cellular components.
- Genetic apparatus, responsible for directing cell function and replication.
Calcium Imbalance:
- Normally tightly regulated within cells.
- Injury can cause calcium influx from the extracellular space and release from mitochondria.
- Elevated calcium activates enzymes, like phospholipases, proteases, ATPases, and endonucleases, causing further damage.
Free Radicals: Reactive chemical species with unpaired electrons, causing widespread damage.
- Involved in chemical and radiation injury, oxygen toxicity, aging, microbial killing, inflammation, and tumor killing.
- Generated through various mechanisms, including:
  - Absorption of radiant energy.
  - Redox reactions, producing superoxide radicals (O2.-), hydrogen peroxide (H2O2), and hydroxyl radicals (OH.-)
  - Enzymatic breakdown of chemicals, like CCl4, which generates free radicals.
- Free radicals react with:
  - Lipid peroxidation of membranes, disrupting their integrity.
  - DNA, causing mutations and damage.
  - Cross-linking of proteins, affecting their function.

Ischemic and Hypoxic Injury

Reversible Injury: Early response to hypoxia.
- Reduces aerobic respiration and ATP production.
- Leads to calcium influx, sodium pump dysfunction, and intracellular water accumulation, causing cell swelling.
- Decreased pH due to lactic acid build-up.
- Reduced protein synthesis.
Irreversible Injury: Prolonged hypoxia leads to:
- Severe mitochondrial damage and calcium accumulation.
- Extensive plasma membrane damage.
- Lysosomal swelling and release of enzymes, leading to cell degradation.
- Loss of cellular contents.

Mechanisms of Irreversible Injury

Progressive loss of membrane phospholipids.
Cytoskeletal abnormalities, leading to cell membrane detachment.
Toxic oxygen radicals produced during reperfusion.
Lipid breakdown products with detergent effects.

Chemical Injury

Two major mechanisms:
- Direct combination with cellular components, like mercury binding to sulfhydryl groups.
- Conversion of chemicals to toxic metabolites, often by P-450 oxidases in the smooth endoplasmic reticulum (SER).

Patterns of Acute Cell Injury

Reversible Injury:
- Light microscopy: Cell swelling, cytoplasmic eosinophilia, fatty change.
- Electron microscopy: Plasma membrane blebbing, mitochondrial swelling, endoplasmic reticulum dilatation, nuclear alterations.
Necrosis:
- Cell death characterized by enzymatic digestion and protein denaturation.
- Appearance: Eosinophilia, vacuolation, calcification (cytoplasm); Karyolysis, pyknosis, karyorrhexis (nucleus).

Types of Necrosis

Coagulative Necrosis: Structural outline of the dead cell is preserved, seen in myocardial infarction.
Liquefactive Necrosis: Cells are digested, forming a liquid mass, seen in bacterial and fungal infections, and in the brain.
Gangrenous Necrosis: Ischemic coagulative necrosis with superimposed infection, often described as "wet gangrene".
Caseous Necrosis: Characteristic of tuberculosis, features a structureless, cheesy appearance.
Fat Necrosis: Occurs in acute pancreatitis, with the release of pancreatic enzymes causing fat destruction.

Apoptosis

Programmed cell death, essential for development and regulation.
Involves single cells or small clusters, with characteristic nuclear fragmentation and formation of apoptotic bodies.
Does not trigger inflammation.
Triggered by:
- Withdrawal of growth factors or hormones.
- Engagement of specific receptors.
- Injury by radiation, toxins, or free radicals.
- Intrinsic protease activation.

Intracellular Accumulations

Cells can accumulate abnormal substances, leading to a variety of conditions.
Categories:
- Excess of normal endogenous substances.
- Normal or abnormal endogenous substances that can't be metabolized due to genetic defects.
- Abnormal exogenous substances that the cell can't break down or transport.

Fatty Change (Steatosis)

Abnormal accumulation of triglycerides, often in the liver.
Can be reversible, but can also occur in heart, skeletal muscle, and kidney.
Caused by toxins, diabetes mellitus, protein malnutrition, obesity, and anoxia.
Excess triglycerides can result from defects in any step of fatty acid entry or lipoprotein synthesis.

Cholesterol and Cholesterol Esters

Macrophages can accumulate cholesterol, becoming "foamy cells".
Important in atherosclerosis, where smooth muscle cells and macrophages become laden with cholesterol esters.
Xanthomas are cholesterol deposits in subcutaneous connective tissues.

Proteins

Less common, but can accumulate in conditions like proteinuria, leading to deposits in kidney tubules.

Glycogen

Accumulates when glucose or glycogen metabolism is disrupted, appearing as clear vacuoles in cells.

Pigments

Melanin: A brown pigment, normally found in skin and hair, can accumulate excessively in freckles.
Hemosiderin: A golden-brown pigment, derived from hemoglobin degradation, accumulates when iron levels are high.

Pathologic Calcification

Abnormal deposition of calcium salts, often with other minerals like magnesium and iron.
Dystrophic Calcification: Occurs in dead or dying tissues, regardless of serum calcium levels.
- Seen in areas of necrosis, atheromas, aging, valvular diseases.
Metastatic Calcification: Occurs in normal tissues when there is hypercalcemia.
- Causes of hypercalcemia include:
  - Hyperparathyroidism.
  - Tumors with increased bone breakdown.
  - Vitamin D intoxication.
  - Sarcoidosis.
  - Advanced renal failure.

Cellular Adaptations of Growth and Differentiation

Cells can adapt to stress by altering their size, number, and function.

Atrophy

Reduction in cell size due to loss of cell substance.
Caused by:
- Decreased workload.
- Loss of innervation.
- Diminished blood supply.
- Inadequate nutrition.
- Loss of endocrine stimulation.
- Aging.
Atrophic cells are smaller but still alive, although they have diminished function.

Hypertrophy

Increase in cell size due to increased synthesis of structural proteins and organelles.
Can be physiologic (due to increased function) or pathologic (due to hormonal stimulation).
Example: Uterine smooth muscle hypertrophy during pregnancy.

Hyperplasia

Increase in the number of cells in a tissue or organ due to increased cell division.
Often occurs alongside hypertrophy.
Can be physiologic:
- Hormonal hyperplasia (breast growth during pregnancy),
- Compensatory hyperplasia (liver regeneration after partial removal)
Pathologic hyperplasia is often caused by excessive hormone or growth factor stimulation.

Metaplasia

Reversible change where one cell type is replaced by another, often to better adapt to an adverse environment.
Example: Transformation of the lining of the bronchus from ciliated columnar epithelium to stratified squamous epithelium in response to chronic irritation from smoking.

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Description

This quiz covers the concepts of cell injury, exploring the mechanisms behind necrosis and apoptosis. It delves into various causes of cell injury, including hypoxia, physical agents, and chemical influences. Test your understanding of how cells respond to stress and injury.