Cells and cell injury

Copyright Information

  • Copyright © 2015 Wolters Kluwer Health | Lippincott Williams & Wilkins

  • Copyright © 2020 Wolters Kluwer • All Rights Reserved

Objectives

  • Understand the structure and function of a eukaryotic cell, including:

    • Nucleus

    • Mitochondria

    • Plasma membrane

  • Understand the P53 enzyme and its role:

    • Regulation of the cell cycle

    • Reducing cancer risk

  • Understand cellular communication processes:

    • Roles of receptors

    • Signal transduction pathways

    • Cellular responses

  • Understand mechanisms of cellular adaptation to stress:

    • Hypertrophy

    • Hyperplasia

    • Atrophy

    • Apoptosis

  • Recognize modes of cellular injury and the progression to cell death.

  • Understand gangrene development and differences between its types.

Functional Components of the Cell

  • Nucleus: Control center of the cell

  • Nuclear Envelope: Membrane surrounding the nucleus

  • Chromosomes and DNA: Genetic material

  • Microtubules: Provide structural support

  • Microfilaments: Aid in movement and shape maintenance

  • Mitochondria: Site of cellular respiration

  • Plasma Membrane: Regulates entry and exit of substances

  • Centrioles: Involved in cell division

  • Vesicles: Transport materials within the cell

  • Lysosome: Digests waste materials

  • Rough Endoplasmic Reticulum: Synthesizes proteins

  • Smooth Endoplasmic Reticulum: Synthesizes lipids

  • Golgi Body: Modifies and packages proteins

Primary Cellular Functions

  • Movement: Muscle cell contraction

  • Conductivity: Creating action potentials across the cell surface

  • Absorption: Intake of substances from surroundings

  • Secretion: Releasing substances into surroundings

  • Excretion: Eliminating waste products

  • Respiration: Metabolizing nutrients to produce energy

  • Reproduction: Making new cells (exception: Neurons and Muscle Cells)

Nucleus: Control Center of the Cell

  • DNA: Contains all genetic information of the body

  • RNA: Copies segments of DNA for protein synthesis

  • Cellular Differentiation: Process by which cells become specialized

A Cell's Life Cycle & Cell Division

  • Phases of the Cell Cycle:

    • G1 (Gap 1): Cell grows and performs its functions

    • S (Synthesis): DNA replication

    • G2 (Gap 2): Prepares for mitosis

    • M (Mitosis): Cell divides into two daughter cells

  • Mitosis Phases:

    • Prophase: Chromosomes condense

    • Metaphase: Chromosomes align at the center

    • Anaphase: Chromosomes separate

    • Telophase: Nuclear membranes form around each set of chromosomes

  • Cytokinesis: Division of cytoplasm following mitosis

DNA Processes

  • DNA Replication: Copying of DNA for cell division

  • DNA Transcription: Process of making messenger RNA (mRNA) from DNA

  • DNA Translation: Synthesizing proteins from mRNA

DNA Replication Errors & Potential Diseases

  • Consequences of Errors:

    • Cancer

    • Hemophilia

    • Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)

    • Mitochondrial Depletion Syndrome (MDS)

The Role of the P53 Gene

  • APC Gene: Destroys β-Catenin to prevent uncontrolled cellular proliferation

  • P53 Protein: Prevents proliferation of mutated cells; crucial in cancer prevention

Mitochondria: Powerplants of the Cell

  • Function: Performs cellular respiration and produces ATP, the energy molecule

Cellular Metabolism

  • Definition: Chemical tasks maintaining essential cellular functions, primarily energy production

Enzymes in Metabolism

  • Function: Catalyze biochemical reactions, manage timing of chemical reactions

  • Example: Amylase catalyzes the digestion of carbohydrates into glucose

Cellular Intake of Nutrients

  • We consume proteins, fats (lipids), and starches (polysaccharides)

  • Breakdown Products:

    • Amino Acids (AAs)

    • Fatty Acids (FAs) & Glycerol

    • Glucose (simple sugars)

  • Process: Nutrients are absorbed, circulated, and taken up by cells to form ATP (Universal Molecular Currency)

  • Metabolic Process: Hydrolysis releases energy through catabolism

Plasma Membrane Structure

  • Composition: Phospholipid bilayer, amphipathic nature, micelle structure

  • Model: Fluid Mosaic Model

Plasma Membrane Structure Components

  • Glycoproteins

  • Carbohydrates

  • Proteins (peripheral and transmembrane)

  • Filament of the cytoskeleton

Plasma Membrane Functionality

  • Transport Mechanisms:

    • Passive Transport:

    • Diffusion, Osmosis, Facilitated Diffusion

    • Active Transport:

    • Primary active transport

    • Secondary active transport: Symport & Antiport

    • Endocytosis: Phagocytosis

    • Exocytosis: Excretion

Cellular Signaling

  • Types of Signal Transduction:

    • Indirect vs. Direct Signaling

  • Neuron Communication: Unique, relies on ion channels

  • Ion Channels: Distribute & balance ions across cell membranes, creating electrical potentials essential for neuron communication

Cell-to-Cell Communication

  • Importance:

    • Regulate growth and division

    • Organize into tissues

    • Coordinate specialized functions

  • Methods of Communication:

    • Gap Junctions

    • Receptors

    • Chemical signaling

  • Consequences of Faulty Communication: Results in malfunction and disease

Causes of Cell Injury

  • Physical Agents:

    • Mechanical forces

    • Extreme temperatures

    • Electrical forces

  • Radiation Injury:

    • Ionizing radiation

    • Ultraviolet radiation

    • Nonionizing radiation

  • Chemical Injury:

    • Drugs, Carbon Tetrachloride, Lead toxicity, Mercury

  • Biologic Agents: Viruses, parasites, bacteria

  • Nutritional Imbalances: Excesses and deficiencies

Mechanisms of Cell Injury: Chemical

  • Free Radicals: Reactive oxygen species (ROS), highly reactive chemical species that cause cell injury

  • Free Radical Injury Consequences:

    • Lipid peroxidation

    • Oxidative modifications of proteins

    • Effects on DNA

Sources of Intracellular Accumulations

  • Normal Body Substances: Lipids, proteins, carbohydrates, etc. (e.g., LDLs related to clogged arteries)

  • Abnormal Endogenous Products: Resulting from inborn errors of metabolism (e.g., diabetes related to insulin & blood glucose)

  • Exogenous Products: Environmental agents and pigments not broken down (e.g., lead causing disruption in enzymes)

Calcification: Accumulation of Calcium in Tissues

  • Types:

    • Dystrophic Calcification: Sign of tissue damage, occurs in damaged tissues

    • Metastatic Calcification: Sign of physical dysfunction (e.g., in end-stage renal disease)

    • Question: Which type is reversible?

Hypoxic Cell Injury**

  • Definition: Decrease in oxygen supply

  • Oxygen's Role: Fuels cellular respiration

  • Reversibility: Possible if restoration occurs quickly; irreversible if prolonged shortage

  • Causes:

    • Decreased oxygen in air

    • Respiratory diseases

    • Impaired oxygen use

    • Edema

    • Ischemia

Cellular Responses to Stress & Injury

  • Responses:

    • Mild Injury: Reversible injury

    • Severe Injury: Irreversible injury

    • Stress exceeding adaptive responses leads to injury or cell death

  • Adaptive Responses:

    • Hypertrophy: Increase in cell size

    • Hyperplasia: Increase in cell number

    • Atrophy: Decrease in cell size

    • Metaplasia: Replacement of one cell type with another

    • Necrosis and Apoptosis: Types of cell death

Reversible Cell Injury

  • Definition: Impairs function but does not cause cell death

  • Types of Reversible Cell Injury:

    • Cellular Swelling: Due to impairment in Na+/K+ ATPase pump; often linked to hypoxia

    • Fatty Change: Linked to fat accumulation in cells

Mechanisms of Acquiring Cellular Injury

  • Mechanical Forces

  • Extreme Temperature

  • Chemical Injuries

  • Radiation Injuries

  • Biological Agents

  • Nutritional Imbalances

Cellular Adaptation

  • Definition: Building resilience by adapting to internal environment changes

  • Methods of Adaptation:

    • Change in size (atrophy, hypertrophy)

    • Change in number (hyperplasia)

    • Change in form (metaplasia)

Results of Cell Adaptation

  • Atrophy: Decrease in cell size

  • Hypertrophy: Increase in cell size

  • Hyperplasia: Increase in cell number

  • Metaplasia: Replacement of adult cells by another type

  • Dysplasia: Deranged cell growth of a specific tissue

Note on Cell Death

  • Necrosis: Cell death occurring in living tissue; interferes with tissue regeneration

Gangrene

  • Definition: Significant tissue necrosis

  • Types:

    • Dry Gangrene:

    • Impaired perfusion leading to dry, shrunken, dark tissue

    • Spreading rate: Slow

    • Wet Gangrene:

    • Bacterial infection leading to cold, swollen, pulseless tissue

    • Symptoms: Moist, black skin, tension, presence of blebs, rapid spreading with foul odor

Questions for Study

  • Question 1: Describes cellular adaptation in chronic cigarette smokers?

    • Answer: Metaplasia (Cell damage induces tougher replacement cells)

  • Question 2: True or False? Dystrophic calcification results from prolonged ischemia.

    • Answer: True (Ischemia stresses tissue, leads to death, and calcium precipitates)

  • Question 3: Best describes the primary function of plasma membrane?

    • Answer: Filtering out harmful substances and protecting the cell from external damage

  • Question 4: Best describes membrane potential?

    • Answer: Electrical potentials existing across membranes as a result of ion distribution