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lecture 1

Nurse 231: Pathopharmacology - Part One: Pathology

Overview of Course Structure

  • The course is divided into two parts:

    • Part One: Pathology

    • Part Two: Pharmacology

  • The structure will alternate between studying pathology and pharmacology throughout the course.

Focus of Today's Lecture

  • Main topics:

    • Human Cell

    • Cellular Injury

    • Adaptation

    • Death

  • There will also be a focus on essential aspects like cellular communication and pathways leading to cellular adaptation and injury, concluding with a discussion of gangrene.

Instructor Information

  • Professor: Chajokio Keke

Course Objectives

  1. Review the basic human cell structure with a focus on aspects relevant to pathology.

  2. Understand key organelles:

    • Nucleus

    • Mitochondria

    • Plasma Membrane

  1. Discuss the DNA replication cycle and the role of enzymes, particularly p53, in cellular function and cancer risk.

  2. Explore cellular communication and its importance in cellular function and adaptation.

  3. Examine types of cellular adaptations and the progression to cellular injury and death.

  4. Define gangrene and its types.

Key Components of the Human Cell

  • Plasma Membrane:

    • Surrounds the cell and regulates the internal environment.

    • Functions:

    • Facilitates communication and nutrient transport.

    • Maintains cellular integrity.

  • Cytoplasm:

    • Gel-like substance inside the plasma membrane.

    • Contains organelles, where metabolic processes occur.

  • Nucleus:

    • Control center of the cell containing DNA.

    • Responsible for transcription of DNA into RNA.

  • Mitochondria:

    • The powerhouse of the cell, organelle where ATP (energy) is produced through cellular respiration.

Human Cell Functions

  • Cells work in coordination as multicellular organisms.

  • Key functions include:

    • Movement (e.g., muscle contractions)

    • Sensory perception (e.g., environmental response)

    • Communication (e.g., neuronal signals)

    • Absorption (e.g., oxygen intake)

    • Secretions (e.g., hormones, enzymes)

    • Excretion (e.g., removal of toxins)

    • Respiration (e.g., oxygen and glucose utilization)

    • Reproduction (cell replication, except for highly specialized cells like neurons)

Key Cellular Processes

DNA Replication Cycle

  • Stages of the cell cycle:

    • G0 Phase: Non-dividing state.

    • G1 Phase: Cell growth and preparation for DNA synthesis.

    • S Phase: DNA synthesis and replication.

    • G2 Phase: Preparation for mitosis (M Phase).

    • M Phase: Mitosis and cytokinesis, resulting in two daughter cells.

Transcription Process

  • RNA Synthesis:

    • The process of copying specific segments of DNA into messenger RNA (mRNA).

    • mRNA guides protein synthesis at ribosomes.

Protein Synthesis

  • mRNA moves to ribosomes, where transfer RNA (tRNA) facilitates the assembly of amino acids into proteins.

Errors in Cellular Processes

  • Mutations can occur during DNA replication, which may lead to diseases (e.g., cancer).

  • Specific examples include:

    • Cancer: Uncontrolled cell proliferation due to genetic mutations.

    • Hemophilia B: Genetic condition resulting from mutations.

  • The importance of p53 Protein:

    • Acts as a tumor suppressor, regulating the cell cycle and DNA repair.

  • Mitochondria have their own DNA, which can also mutate, causing mitochondrial diseases.

Cellular Metabolism

  • Catabolism: Breakdown of substances to generate energy (e.g., from glycogen to glucose for ATP production).

  • Anabolism: Building and synthesizing substances (e.g., synthesizing glycogen from glucose).

  • Enzymes: Proteins that catalyze biochemical reactions. Proper enzyme function requires accurate DNA sequences.

  • Substrate Hydrolysis: Digestion of carbohydrates, proteins, and fats into simpler molecules for metabolism.

Plasma Membrane Structure

  • Phospholipid Bilayer: Contains hydrophilic (water-attracting) heads and hydrophobic (water-repelling) tails.

  • Characteristics:

    • Fluid mosaic model: not rigid, allows flexibility and movement.

    • Proteins embedded within for transport and communication (e.g., channels for glucose transport).

  • Transport Mechanisms:

    • Active Transport: Requires energy (ATP) to move molecules against their concentration gradient (e.g., sodium-potassium pump).

    • Passive Transport: Does not require energy; substances move freely across the membrane (e.g., osmosis for water).

Cell Communication

  • Importance of communication between cells:

    • Essential for maintaining homeostasis and coordinated activity.

  • Types of Signaling:

    • Autocrine: Cell signals itself.

    • Paracrine: Cell signals nearby cells.

    • Endocrine: Hormonal signals across long distances instigated by glands.

Cellular Injury

Causes of Cellular Injury

  1. Physical Agents:

    • Mechanical forces (e.g., trauma), extreme temperatures (hypothermia/hyperthermia).

    • Electrical injuries (e.g., electrocution).

  1. Radiation: Harmful ionizing radiation affecting cellular structures (e.g., DNA damage).

  2. Chemical Agents: Toxic substances (e.g., heavy metals like lead, carbon tetrachloride).

  3. Biological Agents: Viruses, bacteria, and parasites causing infection and inflammation.

  4. Nutritional Imbalances: Excess or deficiencies affecting metabolic processes (e.g., too much cholesterol).

  5. Free Radicals: Highly reactive molecules causing oxidative stress that damages cells.

Types of Cellular Injury Responses

  • Reversible Injury:

    • Cells can recover from mild stress or damage (e.g., temporary hypoxia).

  • Irreversible Injury:

    • Severe damage leading to cell death (e.g., necrosis or apoptosis).

Calcification Related to Cellular Injury

  • Calcification: The pathological deposition of calcium salts in tissues.

  • Dystrophic Calcification: Occurs in damaged, degenerating, or necrotic tissues (e.g., areas of old injury, dead cells, atheromas) despite normal blood calcium levels. It's a sign of previous tissue damage.

  • Metastatic Calcification: Occurs in otherwise normal tissues due to abnormally high levels of calcium in the blood (hypercalcemia). This is typically caused by systemic disturbances rather than direct tissue injury (e.g., hyperparathyroidism, vitamin D toxicity, renal failure).

Cell Adaptation Mechanisms

  1. Atrophy: Decrease in cell size due to decreased workload or stimulation.

  2. Hypertrophy: Increase in cell size indicating greater workload (e.g., muscle growth).

  3. Hyperplasia: Increase in cell number (e.g., in skin cells due to chronic irritation).

  4. Metaplasia: Change of one cell type to another (replacing dysfunctional cells).

  5. Dysplasia: Abnormal growth of cells with loss of cellular orientation and structure.

Types of Cell Death

  • Apoptosis:

    • Programmed cell death, a controlled process not damaging surrounding tissues.

    • Examples include the removal of webbing during development or T-cell mediated destruction of infected cells.

  • Necrosis:

    • Uncontrolled cell death due to injury, leading to inflammation and tissue damage.

Gangrene

  • Expansion of necrosis, typically involving large areas of tissue.

  • Types of Gangrene:

    • Dry Gangrene: Associated with ischemia, leading to shriveled skin and a brownish appearance due to blood supply loss.

    • Wet Gangrene: Due to bacterial infection, characterized by swelling, blackened tissue, and a foul odor indicating rapid spread.

Key Takeaways

  • Pathology is essential in understanding how cellular function goes awry, leading to disease.

  • Communication between cells is