Podcast
Questions and Answers
What is the primary focus of General Pathology?
What is the primary focus of General Pathology?
Which of the following best describes adaptations in cells?
Which of the following best describes adaptations in cells?
Which condition is most directly associated with hypoxia?
Which condition is most directly associated with hypoxia?
What outcome is most likely when a cell cannot maintain homeostasis?
What outcome is most likely when a cell cannot maintain homeostasis?
Signup and view all the answers
Which of the following is NOT a cause of cell injury?
Which of the following is NOT a cause of cell injury?
Signup and view all the answers
What role does ATP depletion play in cell injury?
What role does ATP depletion play in cell injury?
Signup and view all the answers
Which factor does NOT influence the cell's response to injury?
Which factor does NOT influence the cell's response to injury?
Signup and view all the answers
What is the primary consequence of severe mitochondrial damage?
What is the primary consequence of severe mitochondrial damage?
Signup and view all the answers
Which of the following is a characteristic of hypertonic concentrations of glucose or salt?
Which of the following is a characteristic of hypertonic concentrations of glucose or salt?
Signup and view all the answers
How does chronic nutritional excess, such as obesity, contribute to cell injury?
How does chronic nutritional excess, such as obesity, contribute to cell injury?
Signup and view all the answers
What role do reactive oxygen species (ROS) play in cellular injury?
What role do reactive oxygen species (ROS) play in cellular injury?
Signup and view all the answers
Which mechanism leads to membrane damage in ischemic cells?
Which mechanism leads to membrane damage in ischemic cells?
Signup and view all the answers
What consequence does mitochondrial membrane damage have?
What consequence does mitochondrial membrane damage have?
Signup and view all the answers
How does the p53 protein respond to DNA damage?
How does the p53 protein respond to DNA damage?
Signup and view all the answers
What is one of the mechanisms that leads to decreased phospholipid synthesis?
What is one of the mechanisms that leads to decreased phospholipid synthesis?
Signup and view all the answers
Which factor contributes to the activation of p53 in cells?
Which factor contributes to the activation of p53 in cells?
Signup and view all the answers
What can extensive DNA damage lead to if not repaired?
What can extensive DNA damage lead to if not repaired?
Signup and view all the answers
Which of the following can cause direct damage to the plasma membrane?
Which of the following can cause direct damage to the plasma membrane?
Signup and view all the answers
What role does increased cytosolic calcium play in cellular injury?
What role does increased cytosolic calcium play in cellular injury?
Signup and view all the answers
What effect does lysosomal membrane damage have on a cell?
What effect does lysosomal membrane damage have on a cell?
Signup and view all the answers
Study Notes
General Pathology - Introduction
- Pathology is the study of disease processes, examining changes in cells and tissues
- General pathology addresses cellular responses to injury, while systemic pathology focuses on specific organs.
- Key aspects include:
- Etiology: Genetic and environmental factors leading to disease.
- Pathogenesis: Sequence of events leading to disease.
- Morphologic changes : Structural changes in cells and tissues.
- Clinical manifestations: Signs and symptoms of disease.
Cell Homeostasis, Adaptation, and Injury
- Cell Homeostasis: Cells maintain a stable internal environment crucial for optimal function.
-
Adaptations: Reversible changes in cell function and structure in response to physiological or pathological stimuli.
- Adaptations allow cells to survive and function despite environmental changes.
-
Cell Injury: Disruption of cell homeostasis due to harmful influences.
- Can be reversible or irreversible depending on severity of stress.
Loss of Homeostasis & Cell Injury
- When a cell's ability to maintain homeostasis is compromised, it leads to cell injury.
- Sever or prolonged injury can lead to cell death.
Causes of Cell Injury
-
Oxygen Deprivation (Hypoxia):
- Decrease in oxygen supply to cells, leading to cell injury.
- Causes:
- Ischemia: Loss of blood supply due to blocked arteries.
- Inadequate Oxygenation: Respiratory or cardiac failure impairing oxygen delivery.
- Reduced Oxygen-Carrying Capacity: Conditions like anemia or carbon monoxide poisoning.
-
Physical Agents:
- Mechanical trauma, temperature extremes (burns, frostbite), pressure changes, radiation, electric shock.
-
Chemical Agents and Drugs:
- Simple chemicals (glucose, salt) can directly injure cells or disrupt electrolyte balance.
- Toxicity: High concentrations of oxygen can be toxic.
- Environmental/Occupational Hazards: Pollutants, insecticides, herbicides, asbestos, alcohol.
-
Infectious Agents:
- Viruses, bacteria, fungi, parasites.
-
Immunologic Reactions:
- Immune system can cause cell injury in autoimmune diseases.
-
Genetic Abnormalities:
- Chromosomal Abnormalities: Extra chromosomes, as in Down syndrome.
- Single-Gene Mutations: Base pair substitution in sickle cell anemia.
- Protein Function Deficiency: Enzyme defects in metabolic disorders, accumulation of damaged DNA/misfolded proteins.
-
Nutritional Imbalances:
- Deficiencies: Protein-calorie deficiencies, vitamin deficiencies.
- Excesses: Obesity, excessive calorie intake.
-
Cell Aging:
- As cells age, they become more susceptible to injury, contributing to age-related diseases.
Mechanism of Cell Injury
- Nature, Duration, and Severity of Injury:
- The cellular response to injury depends on the nature, duration, and intensity of the harmful stimulus.
- Cell Type, State, and Adaptability:
- The type of cell, its current condition, and its ability to adapt determine its response to injury.
- Individual Variability:
- Genetic differences influence individual responses to the same injurious agent.
- Multiple Interconnected Mechanisms:
- Injurious stimuli often activate multiple interconnected pathways leading to cell damage.
Mitochondrial Damage and Its Role in Cell Injury
-
Mitochondria are crucial for cell survival as they produce ATP.
-
Mitochondrial damage is a critical determinant of cell fate (survival, apoptosis, necrosis).
-
Major Consequences of Mitochondrial Damage:
-
ATP Depletion:
- Caused by mitochondrial damage, reduced oxygen/nutrient supply, exposure to toxins.
- ATP depletion compromises critical cellular functions.
-
Disruption of Cellular Functions:
- Sodium-Potassium Pump Failure: Disrupts ion gradients.
- Altered Metabolism: Shifts to anaerobic glycolysis, leading to acidification.
- Protein Synthesis Impairment: Reduced protein synthesis and increased misfolding.
-
Irreversible Cell Damage and Death:
- Necrosis: Uncontrolled cell death due to severe mitochondrial damage.
- Reactive Oxygen Species (ROS) Generation: Exacerbates cell injury.
- Apoptosis Initiation: Mitochondrial pathway of programmed cell death.
-
ATP Depletion:
Membrane Damage and Its Role in Cell Injury
-
Membrane damage is a consistent feature of cell injury.
-
Mechanisms of Membrane Damage:
- ATP Depletion and Calcium-Mediated Phospholipase Activation: Leads to breakdown of membrane phospholipids.
- Direct Damage by External Agents: Bacterial toxins, viral proteins, physical agents, chemicals.
- Reactive Oxygen Species (ROS): Oxidative damage to cell membranes.
- Decreased Phospholipid Synthesis: Reduced phospholipid production impairs membrane function.
- Increased Phospholipid Breakdown: Increased breakdown of membrane phospholipids.
- Cytoskeletal Abnormalities: Damage to cytoskeletal filaments weakens membrane structure.
-
Consequences of Membrane Damage:
- Mitochondrial Membrane Damage: Decreased ATP production, release of apoptotic proteins.
- Plasma Membrane Damage: Disrupts osmotic balance, loss of cellular contents.
- Lysosomal Membrane Damage: Release of digestive enzymes into cytoplasm, leading to cellular breakdown.
DNA Damage and its Consequences in Cell Injury
-
DNA damage is a critical factor in cell injury, activating cellular responses for repair or elimination of damaged cells.
-
Causes of DNA Damage:
- External Factors: Radiation, chemotherapy, reactive oxygen species (ROS).
- Spontaneous and Aging-Related Damage: Occurs over time.
-
Cellular Response to DNA Damage:
- Activation of p53: Tumor suppressor protein that halts the cell cycle.
- G1 Phase Arrest: Gives the cell time to repair DNA damage.
-
DNA Repair Mechanisms: Activate mechanisms to correct DNA damage.
- Successful Repair: Cell cycle continues.
-
Outcome of Failed DNA Repair:
- Induction of Apoptosis: Programmed cell death.
- Role in Cancer Prevention: Prevents proliferation of cells with potentially oncogenic mutations.
-
Cancer and p53 Mutations:
- Mutations in p53 can impair its ability to arrest the cell cycle or induce apoptosis, increasing the risk of cancer.
Oxidative Stress and Accumulation of Oxygen-Derived Free Radicals
-
Free radicals (ROS) play a significant role in cell injury across various pathological conditions.
-
Overview:
- Free radicals have an unpaired electron, making them highly reactive and capable of damaging essential molecules.
-
Generation of Free Radicals:
- Normal Metabolic Processes: Produced during cellular respiration.
- Radiant Energy: Ultraviolet light and X-rays.
- Inflammation: Activated leukocytes produce ROS bursts.
- Enzymatic Metabolism: Metabolism of certain chemicals or drugs.
- Transition Metals: Iron and copper catalyze free radical formation.
- Nitric Oxide (NO): Can act as a free radical.
-
Removal of Free Radicals:
- Spontaneous Decay: Inherent instability of free radicals.
- Antioxidants: Neutralize free radicals.
- Metal Binding Proteins: Sequester iron and copper to prevent harmful reactions.
-
Enzymatic Defense Mechanisms:
- Catalase: Decomposes hydrogen peroxide.
- Superoxide Dismutases (SODs): Convert superoxide anion.
- Glutathione Peroxidase: Reduces peroxides.
-
Pathological Effects of Free Radicals:
- Lipid Peroxidation: Damage to cell membranes.
- Oxidative Modification of Proteins: Protein damage and inactivation.
- DNA Damage: Single and double-strand breaks, cross-linking, adducts.
-
Physiological and Pathological Roles:
- ROS can induce apoptosis, but can also serve physiological functions in signaling pathways.
Disturbance in Calcium Homeostasis and Its Role in Cell Injury
-
Calcium ions (Ca²⁺) are essential second messengers.
-
Calcium as a Signaling Molecule:
- Under normal conditions, cytosolic Ca²⁺ remains low, but excessive elevation can lead to cell injury.
-
Normal Calcium Homeostasis:
- Low cytosolic Ca²⁺ is maintained by active transport mechanisms.
-
Causes of Calcium Disturbance:
- Ischemia and toxins causing Ca²⁺ release from intracellular stores and influx across the plasma membrane.
-
Mechanisms of Calcium-Induced Cell Injury:
- Mitochondrial Damage: Failure of ATP generation.
-
Enzyme Activation:
- Phospholipases: Breakdown of membrane phospholipids.
- Proteases: Degradation of cytoskeletal and membrane proteins.
- Endonucleases: Fragment DNA and chromatin.
- ATPases: Increased ATP consumption, exacerbating energy depletion.
Clinicopathologic Correlations: Hypoxia, Ischemia, and Reperfusion Injury
-
Hypoxia and Ischemia:
- Ischemia: Reduced blood flow causing tissue injury.
- Hypoxia: Reduced oxygen supply but blood flow is maintained.
Hypoxia vs Ischemia
-
Hypoxia: Reduced oxygen supply with maintained blood flow allows some energy production via anaerobic glycolysis.
-
Ischemia: Absence of blood flow prevents both aerobic and anaerobic metabolism, leading to rapid and severe cell and tissue injury.
Mechanisms of Ischemic Cell Injury
- Oxygen Deprivation: Decreased ATP production due to cessation of oxidative phosphorylation.
- ATP Depletion: Leads to reversible cell injury, such as cell and organelle swelling. Prolonged ischemia results in irreversible injury and necrosis.
Cellular Response to Hypoxia
- HIF-1: Hypoxia-inducible factor 1 promotes angiogenesis, glycolysis, and survival pathways.
- Therapeutic Hypothermia: Lowering body temperature to 92°F is used to minimize ischemic brain and spinal cord injury by reducing metabolic demands, decreasing swelling, suppressing free radicals, and inhibiting inflammation.
Reperfusion Injury
- Oxidative Stress: Reoxygenation leads to reactive oxygen and nitrogen species (ROS/RNS) production, exacerbating injury due to compromised antioxidant defenses during ischemia.
- Intracellular Calcium Overload: Increased calcium influx during reperfusion exacerbates calcium overload from ischemia, leading to mitochondrial permeability transition pore opening, ATP depletion, and further injury.
- Inflammation: Ischemia triggers an inflammatory response with danger signals from dead cells, cytokine secretion, and adhesion molecule expression, attracting neutrophils and causing further damage.
- Complement System Activation: IgM antibodies deposit in ischemic tissues, and upon reperfusion, complement proteins bind and activate, intensifying cell injury and inflammation.
Chemical (Toxic) Injury
-
Direct Toxicity: Some chemicals directly damage cells by interacting with critical molecular components.
- Mercuric Chloride Poisoning: Increases membrane permeability and disrupts ion transport, affecting cells in the gastrointestinal tract and kidneys.
- Cyanide Poisoning: Inhibits cytochrome oxidase, blocking oxidative phosphorylation and leading to cell death.
- Chemotherapeutic Agents and Antibiotics: Many exert cytotoxic effects by damaging targeted cells.
-
Conversion to Toxic Metabolites: Many chemicals are not toxic in their original form but become toxic after being metabolized.
- Carbon Tetrachloride (CCl₄): Converted to a reactive free radical by cytochrome P-450 enzymes, leading to lipid peroxidation and cellular damage.
- Acetaminophen: Metabolized in the liver to a toxic product that can cause liver injury, especially in overdose.
Reversible Cell Injury
- Cellular Swelling: The earliest sign of cell injury, occurs from loss of ion and fluid balance, leading to water accumulation in the cell.
- Fatty Change: Occurs in cells involved in lipid metabolism, particularly the liver, when toxic injury disrupts metabolic pathways and leads to lipid vacuole accumulation.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Description
Test your understanding of general pathology, focusing on the study of disease processes and the cellular responses to injury. This quiz covers key concepts such as etiology, pathogenesis, and cellular adaptations. Dive into what defines cell homeostasis and how injuries impact cellular function.