Essentials of Anatomy and Physiology - Chapter 3: Cells

Cytology and Cellular Foundations

• Cellular Activity:
  • Cellular activity serves as the fundamental foundation for all bodily functions.
  • Cellular dysfunction is the root source of disease.
  • Understanding cellular structure and function forms the essential foundation for the study of anatomy and physiology.
• Cytology:
  • Defined as the scientific study of cellular structure and function.
  • The human body is composed of approximately $200$ distinct kinds of cells.

Major Components of the Cell and Fluid Compartments

• Major Cellular Components:
  • Plasma Membrane (Cell Membrane): Forms the outer surface boundary defining the cell.
  • Cytoplasm: The material contained between the plasma membrane and the nucleus.
  • Nucleus: The largest organelle within the cell.
• Detailed Structures of a Generalized Cell:
  • Surfaces: Apical cell surface, basal cell surface, lateral cell surface, intercellular space, and basement membrane.
  • Cell Extensions and Surface Structures: Microvillus, desmosome, hemidesmosome.
  • Cytoplasmic Structures and Organelles: Centrosome, centrioles, free ribosomes, nucleus, nucleolus, nuclear envelope, mitochondrion, microfilaments, terminal web, Golgi vesicles, Golgi complex, intermediate filament, lysosome, microtubule, rough endoplasmic reticulum, smooth endoplasmic reticulum, fat droplet, and secretory vesicles (including those undergoing exocytosis).
• Cytoplasmic Subdivisions:
  • Cytoskeleton: A supportive framework composed of protein filaments and tubules.
  • Organelles: Diverse compartmentalized structures that perform specific metabolic tasks for the cell.
  • Inclusions: Accumulated cell products such as lipids, pigments, and bacteria.
  • Cytosol: The clear gel (matrix) in which all other cytoplasmic components are embedded.
• Body Fluids:
  • Intracellular Fluid (ICF): Another term for the cytosol contained within cells.
  • Extracellular Fluid (ECF): Refers collectively to all body fluids located outside of cells.
  • Tissue Fluid: The specific ECF located in the spaces between cells.
  • Other ECF Subdivisions: Includes blood plasma, lymph, and cerebrospinal fluid.

Structure and Composition of the Plasma Membrane

• Definition and Function:
  • The plasma membrane defines the physical boundary of the cell.
  • Governs all interactions and communications with other cells.
  • Maintains essential chemical composition differences between the ECF and ICF.
  • Consists of a two-layered lipid film with embedded functional proteins.
• Membrane Faces:
  • Extracellular Face: The outer surface layer facing the extracellular fluid.
  • Intracellular Face: The inner surface layer facing the intracellular fluid.
• Membrane Lipids:
  • Phospholipids:
    • Account for $75BA$ of all membrane lipids.
    • Arranged in a bilayer: Hydrophilic phosphate heads face the water-based environments on both the exterior and interior of the cell, while two hydrophobic fatty acid tails form the middle region away from water.
  • Cholesterol:
    • Accounts for $20BA$ of membrane lipids.
    • Regulates membrane fluidity.
    • Excessive cholesterol inhibits membrane proteins and enzymes; insufficient cholesterol causes the plasma membrane to become excessively fragile.
  • Glycolipids:
    • Account for the remaining $5BA$ of membrane lipids.
    • Composed of phospholipids with short carbohydrate chains attached on the extracellular face.

Functional Roles of Membrane Proteins

• Protein Classes:
  • Integral Proteins: Penetrate into or entirely through the lipid bilayer; most are glycoproteins containing attached carbohydrates.
  • Peripheral Proteins: Do not protrude into the phospholipid bilayer; typically adhere to the intracellular face.
• Specific Functions of Membrane Proteins:
  • Receptors: Specialized to receive and bind chemical signal molecules sent from other cells.
  • Enzymes: Carry out chemical reactions directly at the membrane surface (e.g., degrading signal molecules or breaking down dietary nutrients).
  • Channel Proteins: Contain tunnels that permit water and hydrophilic solutes to enter or exit the cell. Some channels remain constantly open, whereas gated channels open and close in response to specific stimuli (e.g., controlling the firing of the heart's pacemaker).
  • Carriers: Transporters that bind a substance on one side of the membrane and release it on the opposite side; transport glucose, amino acids, ions, and other solutes.
  • Cell-Identity Markers: Glycoproteins and glycolipids that act as unique cellular identification tags, enabling the immune system to distinguish self-cells from foreign entities.
  • Cell-Adhesion Molecules (CAMs): Proteins that physically link cells to one another or to extracellular material, binding tissues together. CAMs are also essential for sperm-egg binding and immune cell attachment.

The Glycocalyx and Cell Surface Extensions

• The Glycocalyx:
  • A fuzzy carbohydrate coat covering the outer surface of cells, formed by the short sugar chains of glycolipids and glycoproteins.
  • Functions: Facilitates cell adhesion, cushions and protects the plasma membrane, determines blood types, and enables the body to distinguish healthy cells from diseased cells, foreign organisms, and transplanted tissues.
  • Associated with the brush border structure, measuring up to $1.0\,\mu\text{m}$ in depth.
• Cell Surface Extensions:
  • Microvilli:
    • Finger-shaped projections of the plasma membrane visible via electron microscopy (indistinct under a light microscope).
    • Function primarily to dramatically increase surface area.
    • Highly developed in cells specialized for absorption (e.g., cells of the small intestine, where they form the brush border).
    • Contain internal cores of actin microfilaments.
  • Cilia:
    • Hair-like extensions of the plasma membrane.
    • Abundant in the mucous membranes of the respiratory tract, where they sweep mucus from the lungs upward toward the throat.
    • Abundant in the uterine tubes, where they move the egg or embryo toward the uterus.
    • Primary Cilium: A single, nonmotile cilium found on most cells that performs sensory functions.
    • Modified Cilia: Serve specialized roles, including light-absorbing components in retinal cells, motion and balance perception in the inner ear, and sensory reception in olfactory cells of the nose.
  • Flagella:
    • Resembles a long, solitary cilium.
    • The only functional flagellum in humans is the tail of a sperm cell, utilized for propulsion along the mucous membrane of the female reproductive tract.
  • Pseudopods:
    • Cytoplasm-filled cellular extensions that continuously alter their shape, ranging from fine filamentous to blunt fingerlike processes.
    • Utilized by specialized cells like macrophages to move around and to engulf invading bacteria.

Intercellular Junctions

• Overview:
  • Structures formed by cell-surface proteins that link cells together and anchor them to extracellular materials.
  • Enable tissues to grow and divide normally, withstand mechanical stress, and communicate directly with one another.
• Three Main Types of Cell Junctions:
  • Tight Junctions:
    • Completely encircle epithelial cells near their upper (apical) edge, fusing adjacent plasma membranes tightly together.
    • Prevents substances from leaking between cells, ensuring that absorbed nutrients pass directly through digestive cells rather than slipping between them.
  • Desmosomes:
    • Patch-like junctions that hold cells together at specific points, preventing them from pulling apart under mechanical stress.
    • Common in tissues subjected to severe stretching, such as the skin and cardiac muscle.
    • Supported internally by intermediate filaments.
  • Gap Junctions:
    • Formed by a ring of proteins surrounding a central pore/channel.
    • Allows direct diffusion of ions, glucose, and other small solutes directly from the cytoplasm of one cell to another.
    • In cardiac muscle, gap junctions allow electrical excitation signals to pass instantly from cell to cell to coordinate contraction.

Mechanisms of Membrane Transport

• Selective Permeability:
  • The plasma membrane selectively allows specific substances to pass while restricting others, maintaining the precise internal conditions necessary for cellular life.
• Filtration:
  • A process in which physical pressure forces fluid through a selectively permeable barrier.
  • Large particles are held back while water and small dissolved solutes pass through.
  • Examples: Water leaving blood capillaries to deliver nutrients to surrounding tissues, and the filtering of blood by the kidneys.
• Simple Diffusion:
  • The net movement of particles down a concentration gradient from an area of high concentration to an area of low concentration.
  • Does not require cellular ATP expenditure; driven entirely by the random kinetic motion of molecules.
  • Nonpolar and hydrophobic substances diffuse directly through the lipid regions of the membrane.
  • Hydrophilic substances diffuse through open protein channels.
• Osmosis:
  • The net movement of water across a membrane from a region of lower solute concentration to a region of higher solute concentration (i.e., down the water concentration gradient).
  • Essential for homeostasis and regulating cell volume (e.g., fluid absorption by blood capillaries).
• Tonicity:
  • The ability of an extracellular solution to alter a cell's intracellular pressure and volume.
  • Determined by the concentration of nonpermeating solutes (particles that cannot cross the membrane).
  • Isotonic Solution: Has a solute concentration equal to that of the ICF. Cells gain and lose water at equal rates, keeping cell volume constant (e.g., intravenous saline therapy).
  • Hypertonic Solution: Has a higher solute concentration than the ICF. Draws water out of the cell via osmosis, causing the cell to shrink (crenate).
  • Hypotonic Solution: Has a lower solute concentration than the ICF. Water flows rapidly into the cell, causing it to swell and potentially rupture (lyse).
• Carrier-Mediated Transport:
  • Facilitated Diffusion:
    • Employs transmembrane carrier proteins to move solutes that cannot cross the lipid bilayer independently.
    • Moves solutes down their concentration gradient (from high to low concentration).
    • Requires no energy (ATP) expenditure by the cell.
    • Example: Absorption of sugars from digested food into mucosal cells.
  • Active Transport:
    • Employs carrier proteins to move solutes up their concentration gradient (from low concentration to high concentration).
    • Requires direct energy input in the form of ATP; transport halts immediately if ATP production stops.
  • Sodium-Potassium Pump ($\text{Na}^+/\text{K}^+$ Pump):
    • A crucial active transport process consuming a significant portion of daily caloric expenditure.
    • Sodium ($\text{Na}^+$) is maintained at higher concentrations in the ECF, while potassium ($\text{K}^+$) is maintained at higher concentrations in the ICF.
    • Binds and pumps $3\,\text{Na}^+$ out of the cell while simultaneously binding and pumping $2\,\text{K}^+$ into the cell per cycle.
    • Functions: Controls cellular volume, generates body heat, and provides potential energy to drive other transport pumps.

Vesicular Transport Mechanisms

• Overview:
  • Transports large particles, fluid droplets, or numerous molecules simultaneously across the plasma membrane inside bubble-like membrane vesicles.
  • Requires continuous expenditure of ATP energy.
• Endocytosis:
  • Processes that bring external matter into the cell.
  • Phagocytosis ("Cell Eating"):
    • Foot-like pseudopods extend from the cell to surround a foreign particle or microorganism, engulfing it into a membrane-bound vesicle called a phagosome where it is enzymatically degraded.
    • Prominent in white blood cells known as macrophages, which clean up tissues.
  • Pinocytosis ("Cell Drinking"):
    • Occurs in all human cells.
    • Begins with dimpling of the plasma membrane, which then caves inward and pinches off to form internal vesicles containing droplets of ECF.
  • Receptor-Mediated Endocytosis:
    • A highly selective form of endocytosis.
    • Specific target molecules in the ECF bind to complementary receptor proteins clustered together on the plasma membrane.
    • The membrane sinks inward at the receptor site, pinching off to form a vesicle carrying the concentrated target molecule (e.g., uptake of insulin from the bloodstream).
• Exocytosis:
  • The process of exporting material out of the cell (endocytosis in reverse).
  • A intracellular secretory vesicle migrates to the cell surface and fuses with the plasma membrane, releasing its contents into the ECF.
  • The membrane of the vesicle integrates directly into the plasma membrane.
  • Examples: Secretion of digestive enzymes by pancreatic glands, release of milk components by mammary gland cells.

The Cytoskeleton

• Overview:
  • A intricate network of protein filaments and tubules distributed throughout the cytoplasm.
  • Structurally supports the cell, determines shape, organizes organelle locations, transports materials internally, contributes to cell movements, and anchors to plasma membrane proteins.
• Cytoskeletal Components:
  • Microfilaments:
    • The thinnest cytoskeletal components, measuring approximately $6\,\text{nm}$ in diameter.
    • Composed of the protein actin.
    • Form the structural cores of microvilli and a dense fibrous network on the internal plasma membrane face called the terminal web.
  • Intermediate Filaments:
    • Stiff components measuring $8\text{ to }10\,\text{nm}$ in diameter.
    • Provide structural support and strength to desmosomes.
    • Composed of tough proteins such as keratin, which fills epidermal skin cells to impart mechanical strength.
  • Microtubules:
    • The thickest cytoskeletal components, measuring $25\,\text{nm}$ in diameter.
    • Hold organelles in place, form structural bundles that maintain cell shape, and form the mitotic spindle and centrioles.

Structure and Function of Cellular Organelles

• Nucleus:
  • The largest cellular organelle; functions as the genetic control center.
  • Most cells possess a single nucleus; mature red blood cells have none (anucleate), whereas skeletal muscle cells contain multiple nuclei (multinucleate).
  • Nuclear Envelope: A double-membrane structure enclosing the nucleus, perforated by nuclear pores that regulate molecular traffic into and out of the nucleus and hold the two membranes together.
  • Nucleoli: One or more dense masses within the nucleus where ribosomal subunits are synthesized.
  • Chromosomes and Chromatin:
    • Chromosomes are threadlike bodies composed of DNA and protein present during cell division; most human cells contain $46$ chromosomes.
    • Chromatin refers to the fine, uncoiled filaments of DNA dispersed throughout the nucleus during non-dividing stages.
• Endoplasmic Reticulum (ER):
  • A continuous network of interconnected membranous channels called cisternae.
  • Synthesizes steroids and other lipids, detoxifies drugs, and manufactures cellular membranes, phospholipids, and proteins.
  • Rough Endoplasmic Reticulum (Rough ER):
    • Cisternae are studded with ribosomes.
    • Continuous with the outer membrane of the nuclear envelope.
    • Extremely abundant in cells actively involved in massive protein synthesis.
  • Smooth Endoplasmic Reticulum (Smooth ER):
    • Cisternae lack attached ribosomes.
    • Continuous with the Rough ER.
    • Abundant in cells that synthesize steroid hormones (e.g., testes and ovaries) and cells specialized in drug and toxin detoxification (e.g., liver cells).
• Ribosomes:
  • Small granules composed of ribosomal RNA (rRNA) and proteins.
  • Subunits are assembled in the nucleolus and exported to the cytoplasm.
  • Read genetic messenger molecules from the nucleus and translate them to assemble amino acids into proteins.
  • Found attached to the nuclear envelope and Rough ER, or floating free in the cytosol.
• Golgi Complex:
  • A cluster of small, flattened, curved membranous sacs called cisternae.
  • Synthesizes carbohydrates and puts the finishing touches on protein and glycoprotein synthesis.
  • Golgi Vesicles: Membranous sacs that pinch off from the edges of Golgi cisternae carrying modified secretory products. Some vesicles become lysosomes, some integrate into the plasma membrane, and others become secretory vesicles for exocytosis (e.g., release of breast milk).
• Lysosomes:
  • Membrane-enclosed packages containing digestive enzymes, typically round or oval in shape.
  • Function to break down unneeded intracellular molecules, ingested microbes, and worn-out organelles.
  • Execute programmed cell death (apoptosis).
• Peroxisomes:
  • Membrane-enclosed sacs resembling lysosomes but containing distinct oxidative enzymes.
  • Abundant in liver and kidney cells.
  • Break down fatty acids into two-carbon molecules that can be utilized for ATP synthesis.
  • Neutralize free radicals, detoxify alcohol and drugs, kill bacteria, and produce hydrogen peroxide ($\text{H}_2\text{O}_2$).
• Mitochondria:
  • Organelles specialized for synthesizing cellular ATP.
  • Surrounded by a double membrane: The inner membrane features deep infoldings called cristae, which contain the enzyme complexes responsible for generating the majority of cellular ATP.
  • Mitochondrial Matrix: The internal space between cristae containing enzymes, ribosomes, and a small circular DNA molecule designated as mitochondrial DNA (mtDNA).
  • Evolutionary Origin: Evolved from primitive free-living bacteria that were internalized by an ancestral eukaryotic cell. mtDNA closely resembles bacterial DNA and is distinct from nuclear DNA. Mutations in mtDNA cause specific metabolic diseases affecting muscle, heart, and eye tissues.
• Centrioles and Centrosomes:
  • Centrioles: Short, cylindrical assemblies composed of organized microtubules.
  • Centrosome: A specialized clear area of cytoplasm near the nucleus containing a pair of perpendicular centrioles; plays a critical role in organizing spindle fibers during cell division.

Molecular Mechanisms of Protein Synthesis

• Overview of Protein Synthesis:
  • Genes contained on nuclear DNA code for the production of specific proteins.
  • Step 1: Transcription: The synthesis of a messenger RNA (mRNA) copy of a gene in the nucleus.
  • Step 2: Translation: The reading of the mRNA code by ribosomes in the cytoplasm to assemble amino acids in the precise order specified by DNA.
• Transcription Steps:
  1. An unzipping enzyme uncoils and opens the DNA double helix at the site of the target gene, exposing the bases of the coding strand.
  2. An RNA-synthesizing enzyme reads the exposed DNA bases on the coding strand, draws free RNA nucleotides from the nuclear pool, and links them into a single-stranded mRNA molecule.
  3. Base Pairing Rules:
     • Thymine ($\text{T}$) on DNA pairs with Adenine ($\text{A}$) on mRNA.
     • Guanine ($\text{G}$) on DNA pairs with Cytosine ($\text{C}$) on mRNA (and vice versa).
     • Adenine ($\text{A}$) on DNA pairs with Uracil ($\text{U}$) on mRNA.
     • Example: A DNA sequence of $\text{TACCGTCCA}$ produces a complementary mRNA sequence of $\text{AUGGCAGGU}$.
  4. mRNA Processing: The raw mRNA transcript is edited inside the nucleus; noncoding segments are spliced out, and coding segments are joined together to form mature mRNA, which then exits through nuclear pores into the cytoplasm.
• Translation Steps:
  1. A two-part ribosomal subunit complex (composed of rRNA and protein) binds to the mature mRNA strand and moves along its length, reading its sequence.
  2. Genetic Code and Codons: The genetic message on mRNA is organized into three-base units called codons, each specifying a particular amino acid (e.g., codon $\text{AUG}$ codes for methionine).
  3. Transfer RNA (tRNA) Interaction:
     • Each tRNA molecule carries a specific amino acid and features a three-base anticodon that is complementary to a specific mRNA codon.
     • Example: An mRNA codon of $\text{GGU}$ selectively binds a tRNA molecule bearing the anticodon $\text{CCA}$.
  4. As the ribosome advances codon-by-codon, tRNAs deliver their respective amino acids, which the ribosome links together via peptide bonds to grow the polypeptide chain. Once the amino acid is delivered, the free tRNA dissociates to pick up another amino acid.
  5. Upon reaching a stop codon, the ribosome releases the completed polypeptide and dissociates from the mRNA.
• Protein Processing and Secretion:
  • For proteins destined for lysosomes or secretion, the ribosome-mRNA complex docks onto the Rough ER during assembly.
  • The growing protein is spooled directly into the ER cisterna, where specific amino acid sequences may be cut and spliced.
  • Transport vesicles bud off from the ER and deliver the altered protein to the Golgi complex.
  • The Golgi complex modifies (e.g., adding carbohydrate chains), sorts, and passes the protein through its cisternae.
  • Golgi vesicles containing the final product bud off, becoming lysosomes or migrating to the plasma membrane for exocytosis.

The Cell Cycle and DNA Replication

• The Cell Cycle:
  • The lifecycle of a cell extending from one cell division to the next.
  • Divided into four primary phases:
    • $\text{G}_1$ (First Gap Phase)
    • $\text{S}$ (Synthesis Phase)
    • $\text{G}_2$ (Second Gap Phase)
    • $\text{M}$ (Mitotic Phase)
• Interphase:
  • Consists of the collective time spanning the $\text{G}_1$, $\text{S}$, and $\text{G}_2$ phases (the period between active cell divisions).
• First Gap Phase ($\text{G}_1$):
  • The interval between a previous cell division and DNA replication.
  • Characterized by vigorous protein synthesis, cellular growth, and performance of normal metabolic tasks.
  • Centrioles begin replicating, and materials needed for DNA replication are accumulated.
• Synthesis Phase ($\text{S}$):
  • The dedicated phase for DNA replication.
  • The DNA double helix unzips into two separate single strands.
  • DNA Polymerase: The enzyme that reads the exposed base sequence on an old DNA strand and matches free nucleotides from the pool to build a new complementary strand. Two DNA polymerase enzymes work simultaneously in opposite directions on the two unzipped strands.
  • Semiconservative Replication: Each resulting double-stranded DNA molecule is composed of one original parent strand and one newly synthesized daughter strand.
• Second Gap Phase ($\text{G}_2$):
  • A relatively brief interval occurring between DNA replication and active cell division.
  • Centriole replication is completed.
  • Enzymes that control and direct cell division are synthesized.
• Mitotic Phase ($\text{M}$):
  • The period of nuclear division (mitosis) and cytoplasmic division (cytokinesis).
  • The nucleus replicates its content, dividing the genetic material into two identical sets.
  • At the conclusion of the $\text{M}$ phase, the cell pinches in two to yield two genetically identical daughter cells.

Mitosis and Cytokinesis

• Division Mechanisms:
  • Mitosis: Somatic cell division used for body growth (development of a fertilized egg into an individual, organ growth after birth) and repair of damaged tissues.
  • Meiosis: Specialized cell division producing gametes (sperm and egg cells).
• Phases of Mitosis:
  1. Prophase:
     • Chromatin condenses and coils into short, dense, visible rods (chromosomes), making genetic material easier to distribute.
     • Each chromosome consists of two genetically identical bodies called sister chromatids, joined together at a pinched central point called the centromere.
     • The cell contains $46$ chromosomes, each comprising $2$ chromatids ($92$ DNA molecules total).
     • The nuclear envelope disintegrates, releasing chromosomes into the cytosol.
     • Spindle fibers (elongated microtubules) sprout from centrioles and push centriole pairs apart to opposite poles of the cell.
     • Spindle fibers attach to centromeres and tug chromosomes until they align along the midline of the cell.
  2. Metaphase:
     • Chromosomes are fully aligned along the cell equator (midline).
     • Spindle fibers form a complete mitotic spindle; some fibers stretch from centrioles to centromeres, while others anchor the assembly to the inner plasma membrane.
  3. Anaphase:
     • An enzyme cleaves each centromere in two, separating sister chromatids into individual, genetically identical daughter chromosomes.
     • Spindle fibers shorten and pull daughter chromosomes toward opposite poles of the cell, led by their centromeres with chromosome arms trailing behind.
     • Ensures both future daughter cells receive an identical, complete set of genes.
  4. Telophase:
     • Daughter chromosomes gather in clusters at each pole of the cell.
     • Chromosomes uncoil and return to the dispersed chromatin state.
     • A new nuclear envelope forms around each chromosome cluster, and new nucleoli appear within each nucleus.
     • The mitotic spindle vanishes, marking the completion of nuclear division.
• Cytokinesis:
  • The division of the cytoplasm, which overlaps chronologically with telophase.
  • Initiated by the appearance of a crease called the cleavage furrow surrounding the cell equator.
  • The cell pinches entirely in two, forming two separate, genetically identical daughter cells that transition into interphase to begin a new cell cycle.
• Summary of Mitotic Stage Events:
  • Chromosome Alignment at Equator: Occurs during Metaphase.
  • Chromosome Coiling and Chromatid Visibility: Occurs during Prophase.
  • Centromere Splitting and Chromatid Separation: Occurs during Anaphase.
  • New Nuclear Envelope Formation: Occurs during Telophase.