Marieb Human Anatomy and Physiology: Cells the Living Units Notes

Cells: The Structural and Functional Units of All Living Things

• Definition of Cells: Cells are the structural units of all living things.
• Cell Count: The human body is composed of approximately $50$ to $100$ trillion cells.
• Cell Theory Fundamentals:     * The cell is the smallest unit of life.     * All organisms consist of one or more cells.     * Cells arise exclusively from pre-existing cells.
• Cell Diversity:     * The human body contains over $250$ different types of cells.     * Variation in size, shape, and subcellular components leads to specialized functions.     * Types Based on Function:         * Connection, Linings, and Gas Transport: Fibroblasts, Erythrocytes (red blood cells), and Epithelial cells.         * Movement: Skeletal muscle cells and Smooth muscle cells.         * Nutrient Storage: Fat cells.         * Immune Defense: Macrophages.         * Information Gathering and Control: Nerve cells.         * Reproduction: Sperm cells.

The Generalized Cell and Extracellular Materials

• The Generalized Cell: While cells differ, they share common structures and functions organized into three basic parts:     1. Plasma Membrane: A flexible outer boundary.     2. Cytoplasm: Intracellular fluid containing metabolic machinery called organelles.     3. Nucleus: The DNA-containing control center.
• Extracellular Materials: Substances found outside the cells, categorized into:     * Extracellular Fluids (ECFs):         * Interstitial Fluid: The fluid in which cells are submersed or "bathed."         * Blood Plasma: The fluid component of blood.         * Cerebrospinal Fluid: The fluid surrounding the organs of the nervous system.     * Cellular Secretions: Includes substances such as saliva, mucus, and gastric fluids.     * Extracellular Matrix (ECM): A substance that acts as a "glue" to hold cells together.

Structure of the Plasma Membrane

• Definition and Function: The plasma membrane is an active, selectively permeable barrier separating intracellular fluid (ICF) from extracellular fluid (ECF). It controls what enters and exits the cell.
• Fluid Mosaic Model: Depicts the membrane as a moving structure made of many pieces:     * A bilayer of phospholipids with embedded proteins.     * Smaller amounts of cholesterol dispersed within.     * Surface sugars forming the glycocalyx.     * Specific junctions to hold cells together.
• Membrane Lipids:     * Phospholipids: Comprise the majority of the bilayer. Consist of polar (charged), hydrophilic "heads" and nonpolar (uncharged), hydrophobic fatty acid "tails."     * Cholesterol ($20\%$): Located between phospholipid tails to increase the stiffness of the membrane.

Membrane Proteins and Their Specialized Tasks

• Overview: Proteins make up about half the mass of the plasma membrane. They allow communication with the environment and perform specialized functions.
• Types of Membrane Proteins:     * Integral Proteins: Deeply inserted into the membrane. Most are transmembrane proteins (span the entire membrane). They have hydrophobic regions to interact with lipid tails and hydrophilic regions to interact with water.     * Peripheral Proteins: Loosely attached to integral proteins or anchored to the membrane surface.
• Six Primary Protein Functions:     1. Transport: Proteins provide hydrophilic channels selective for solutes or use $ATP$ to pump substances (carriers/pumps).     2. Receptors for Signal Transduction: Extracellular binding sites for chemical messengers (e.g., hormones) that initiate chemical reactions (signal transduction).     3. Enzymatic Activity: Enzymes catalyze sequential steps of metabolic pathways.     4. Cell-Cell Recognition: Glycoproteins (proteins bonded to short sugar chains) act as identification tags for short-lived recognition between cells.     5. Cell-to-Cell Joining: Proteins hook together for long-lasting junctions (e.g., tight or gap junctions). Cell adhesion molecules (CAMs) guide migration.     6. Attachment to Cytoskeleton and ECM: Maintain cell shape, fix protein locations, and play roles in movement.

The Glycocalyx and Intercellular Junctions

• Glycocalyx: A "sugar coating" of carbohydrates (glycolipids and glycoproteins) extending from the cell surface. It serves as a biological marker for recognition, allowing the immune system to distinguish "self" from "nonself."     * Clinical Relevance: Cancer cell glycocalyces change rapidly, allowing the mutated cells to evade immune destruction and replicate.
• Types of Intercellular Junctions:     * Tight Junctions: Integral proteins fuse together to form an impermeable barrier encircling the cell, preventing fluid movement between cells.     * Desmosomes (Anchoring Junctions): Linker proteins (cadherins) interlock like a zipper. These are anchored internally by "button-like" plaques and keratin filaments to prevent tearing.     * Gap Junctions: Transmembrane proteins (connexons) form hollow tunnels that allow ions and small molecules to pass between cells. These are vital for electrical signaling in cardiac and smooth muscle.

Passive Membrane Transport: Diffusion and Osmosis

• Passive Transport: Requires no cellular energy ($ATP$). Molecules move down their concentration gradient using intrinsic kinetic energy.
• Factors Influencing Diffusion Speed:     1. Concentration: Steeper gradients result in faster diffusion.     2. Molecular Size: Smaller molecules diffuse faster.     3. Temperature: Higher temperatures increase kinetic energy and speed.
• Types of Passive Transport:     * Simple Diffusion: Nonpolar, lipid-soluble (hydrophobic) substances (e.g., oxygen, carbon dioxide, steroids, fatty acids) pass directly through the phospholipid bilayer.     * Facilitated Diffusion: Assisted transport of hydrophobic/larger molecules.         * Carrier-mediated: Substances bind to transmembrane integral proteins that change shape to envelop and move the molecule.         * Channel-mediated: Movement through aqueous-filled cores. Includes "leakage channels" (always open) and "gated channels" (controlled by chemical or electrical signals).     * Osmosis: The movement of water through the bilayer or via specific channels called aquaporins (AQPs). Water moves from areas of low solute (high water) concentration to high solute (low water) concentration.
• Osmolarity: The total concentration of all solute particles in a solution, expressed in osmoles/liter ($osmol/L$).
• Osmotic Pressures:     * Hydrostatic Pressure: Back pressure exerted by water against the cell wall/membrane.     * Osmotic Pressure: Tendency of water to move into the cell.

Tonicity and Cellular Shapes

• Tonicity: The ability of a solution to change the shape or tension of a cell by altering internal water volume.
• Isotonic Solution: Same osmolarity as the cell; total volume remains unchanged.
• Hypertonic Solution: Higher osmolarity than inside the cell; water flows out, causing the cell to shrink (crenation).
• Hypotonic Solution: Lower osmolarity than inside the cell; water flows in, causing the cell to swell and potentially burst (lysing).
• Clinical Note: Damaged plasma membranes (e.g., in burn patients) lose the ability to maintain concentration gradients, leading to the loss of precious fluids and ions.

Active Membrane Transport

• Active Processes: Require energy ($ATP$) to move solutes against their concentration gradient (low to high).
• Primary Active Transport: Energy comes directly from the hydrolysis of $ATP$ by pump proteins.     * Sodium-Potassium ($Na^+-K^+$) Pump: An enzyme called $Na^+-K^+$ ATPase pumps $3$ $Na^+$ out and $2$ $K^+$ into the cell per $ATP$ molecule. This maintains electrochemical gradients essential for nerve and muscle function.
• Secondary Active Transport (Cotransport): Uses energy stored in concentration gradients established by primary transport.     * Symporters: Transport two different substances in the same direction.     * Antiporters: Transport one substance in and another out.

Vesicular Transport

• Definition: Movement of large substances or amounts within membranous sacs called vesicles.
• Types of Vesicular Transport:     * Transcytosis: Moving substances into, across, and then out of the cell.     * Vesicular Trafficking: Moving substances between areas or organelles within a cell.     * Endocytosis: Transport into the cell.         * Phagocytosis ("Cell Eating"): Pseudopods flow around solid particles, forming a phagosome. Used by macrophages.         * Pinocytosis ("Cell Drinking"): Nonspecific infolding of the membrane to sample extracellular fluid and dissolved solutes.         * Receptor-Mediated Endocytosis: Highly selective process involving receptors to concentrate materials like enzymes, hormones (insulin), and low-density lipoproteins (LDLs). Pathogens like flu viruses can hijack this.     * Exocytosis: Ejection of material (hormones, neurotransmitters, mucus) from the cell. Involves docking proteins called v-SNAREs (on the vesicle) and t-SNAREs (on the target membrane) that trigger fusion and pore formation.

Membrane Potential

• Resting Membrane Potential (RMP): Voltage across the membrane in its resting state, typically ranging from $-50$ to $-100\,mV$. The negative sign indicates the interior is more negative than the exterior.
• Generating RMP: $K^+$ is the primary determinant. $K^+$ leaks out down its concentration gradient, leaving behind negative charge. It is pulled back by the electrical gradient. Equilibrium is usually reached around $-90\,mV$.
• Maintaining RMP: The $Na^+-K^+$ pump maintains the steady state by continuously counteracting the leakage of ions.

Cell Interaction Mechanisms

• Cell Adhesion Molecules (CAMs): Functions include anchoring cells, assisting movement, attracting white blood cells (WBCs) to injury, and transmitting intracellular signals for growth.
• Membrane Receptors:     * Contact Signaling: Direct touch for development and immunity.     * Chemical Signaling: Interaction between ligands (neurotransmitters, hormones) and receptors.     * G Protein-Coupled Receptors: Relays that use a G protein intermediary to activate enzymes or release second messengers (e.g., cyclic $AMP$ or calcium) inside the cell.

Cytoplasmic Organelles

• Cytoplasm Components: Cytosol (gel solution), Inclusions (insoluble molecules like glycogen or pigments), and Organelles.
• Membranous Organelles:     * Mitochondria: "Power plants" that produce $ATP$ via aerobic respiration. Feature inner folds called cristae and contain their own DNA, RNA, and ribosomes. They reproduce via fission.     * Endoplasmic Reticulum (ER):         * Rough ER: Studded with ribosomes; synthesizes secreted proteins, membrane proteins, and phospholipids.         * Smooth ER: Involved in lipid metabolism, steroid hormone synthesis, detoxification (liver/kidneys), glycogen conversion, and calcium storage (sarcoplasmic reticulum in muscle).     * Golgi Apparatus: Stacked cisterns that modify, concentrate, and package proteins/lipids into vesicles (secretory vesicles, membrane vesicles, or lysosomes).     * Lysosomes: Bags of acid hydrolases that digest bacteria/toxins and degrade nonfunctional organelles.         * Tay-Sachs Disease: Genetic lack of an enzyme to break down glycolipids in nerve cells, leading to blindness and death by age $5$.     * Peroxisomes: Contain oxidases (neutralize toxins to $H_2O_2$) and catalase (converts $H_2O_2$ to $H_2O$). Also handle fatty acid metabolism.
• Nonmembranous Organelles:     * Ribosomes: Sites of protein synthesis. Standard switchable forms: Free (cytosolic proteins) and Membrane-bound (secreted/membrane proteins).     * Cytoskeleton: Network of rods including Microfilaments (actin for strength/motility), Intermediate Filaments (rope-like fibers for resisting pull), and Microtubules (tubulin tubes for cell shape and organelle tracks).     * Centrosome/Centrioles: Microtubule organizing center consisting of a granular matrix and a pair of barrel-shaped centrioles ($9$ triplets of microtubules).

Cellular Extensions

• Cilia: Whiplike extensions used to move substances across cell surfaces (e.g., mucus in the respiratory tract). Move via a power stroke and recovery stroke.
• Flagella: Longer projections that propel the cell (e.g., sperm tail).     * Structure: Cilia and flagella have a "$9 + 2$" microtubule pattern.
• Microvilli: Fingerlike extensions designed to increase surface area for absorption, containing an actin microfilament core.

The Nucleus and Chromatin

• Structure:     * Nuclear Envelope: Double-membrane barrier with circular nuclear pores. The inner layer is the nuclear lamina (protein mesh for shape).     * Nucleoli: Dense bodies for ribosomal RNA ($rRNA$) synthesis.     * Chromatin: Composed of $30\%$ DNA, $60\%$ histone proteins, and $10\%$ RNA.
• Functional Units: Nucleosomes are DNA wrapped twice around eight histone proteins. Chromosomes are condensed chromatin protecting DNA during division.

The Cell Cycle and DNA Replication

• Interphase: Routine activities and preparation for division.     * $G_1$: Growth and metabolism (permanently ceased cells enter $G_0$).     * S (Synthesis): DNA replication.     * $G_2$: Final preparation for division.
• DNA Replication Steps:     1. Uncoiling: Enzymes unwind the double helix.     2. Separation: Strands unzip at the replication fork.     3. Assembly: DNA polymerase builds a leading strand (continuously) and a lagging strand (discontinuously in segments). DNA ligase splices segments.     * Semiconservative Replication: Each new DNA molecule contains one old and one new strand.

Mitosis and Cytokinesis

• Mitosis (Nuclear Division):     1. Prophase: Chromatin condenses into chromosomes (sister chromatids joined by centromere). The mitotic spindle forms from centrosomes. The nuclear envelope fragments.     2. Metaphase: Chromosomes align at the equator (metaphase plate).     3. Anaphase: Centromeres split; sister chromatids are pulled toward opposite poles.     4. Telophase: Chromosomes uncoil into chromatin, nuclear membranes reform, and the spindle disappears.
• Cytokinesis: Division of the cytoplasm via a contractile ring of actin resulting in a cleavage furrow.
• Control Mechanisms: Ratio of surface area to volume, growth factors, and checkpoints (especially the $G_1$ restriction point). Contact inhibition prevents overgrowth.

Protein Synthesis (Transcription and Translation)

• Genetic Code: DNA triplets are segments of three bases that specify amino acids. Genes contain coding exons and noncoding introns.
• Transcription (DNA to mRNA): Occurs in the nucleus. RNA polymerase binds to a promoter, elongates the RNA strand by matching bases (Uracil replaces Thymine), and terminates at a signal. Spliceosomes remove introns to create functional mRNA.
• Translation (mRNA to Protein): Occurs in the cytoplasm at ribosomes.     * Codons: Three-base sequences on mRNA ($64$ possible).     * Anticodons: Complementary three-base sequences on tRNA that carry specific amino acids.     * Ribosome Sites: A (aminoacyl), P (peptidyl), and E (exit).     * Polyribosome Arrays: Multiple ribosomes translating one mRNA simultaneously.
• mRNA Vaccines: Use mRNA coding for pathogen-specific spike proteins (e.g., COVID-19) to train the immune system.

Cellular Life Cycle and Aging

• Disposal:     * Autophagy: Disposing of unneeded organelles via autophagosomes.     * Ubiquitin-Proteasome Pathway: Marking misfolded proteins with ubiquitin for destruction by proteasomes.     * Apoptosis: Programmed cell death involving caspases that degrade DNA and the cytoskeleton.
• Developmental Aspects:     * Cell Differentiation: Development of specific features as certain genes are turned on or off.     * Hyperplasia: Accelerated growth increasing cell numbers.     * Atrophy: Decrease in cell size due to loss of stimulation/use.
• Theories of Aging:     * Genetic Theory: Mitosis cessation is programmed. Telomeres (protective nucleotide strings) shorten with every division. Telomerase (found in embryos and cancer) can lengthen them.
• Progeria: A rare disease causing rapid aging due to defective progerin protein destabilizing the nuclear lamina. Treated by lonafarnib (Zokinvy).