Comprehensive Human Physiology Notes

Page 1: Introduction to Human Physiology

• Instructor: Dr. Jason Ortega • He / Him
• Contact: jason.ortega@uafs.edu
• Office: MS 238F
• Office Hours: TBA & By appointment

Page 2: Lecture Tips

• Attend lecture regularly
• Rewrite the lecture notes
• Use the textbook to fill gaps or look up topics
• Focus studying on the lecture notes
• After rewriting notes, take the chapter quiz
• After each quiz, review every question
• For integrative material: walk through the steps verbally, draw sketches, and “teach the concepts” to another person
• Ask for help!

Page 3: Core Concepts – Anatomy vs Physiology

• Anatomy – What? Where? Study of external/internal structures; naming parts; how parts fit together
• Anatomy dictates physiology; specific anatomical structures have specific physiological functions
• Physiology – How? Why? Study of how the body functions from first principles
• Homeostatic mechanisms: how the body reacts to changes and strives to return to baseline ranges
• Time scales:
  • Acute: rapid & short; seconds to minutes
  • Chronic: slow & long lasting; minutes to hours to days

Page 4: Levels of Biological Organization (Scale) and Organ Systems

• Size & level definitions:
  • Molecules (Chemical/Molecular Level): 0.1 nm
  • Complexes: 10 nm
  • Contractile protein fibers: 10 µm
  • Cardiac muscle cells & tissue organization: 1 mm
  • Heart walls built from cardiac muscle tissue
  • Tissue Level: 120 mm (organ-level context varies by organism)
  • Organ Level: The heart is a complex 3D organ
  • Organ System Level: Endocrine, Cardiovascular, Lymphatic, Respiratory, Digestive, Urinary, Reproductive, Nervous, Muscular, Integumentary, Skeletal
  • Organism Level: All organ systems work together to keep the body healthy
  • Organism example: Humans composed of 11 organ systems; reproduction transmits genes; phenotype influenced by genes and environment
• Organ systems illustrated in the cardiovascular integration context
• The cardiovascular system components: heart, blood, blood vessels
• Organism-level integration: 11 organ systems; interdependence

Page 5: Hierarchy of Biological Organization (Continued)

• Molecules dictate structure and function of cells
• Cellular Level: smallest living unit; contains organelles
• Tissue Level: cells plus surrounding material
• Organ Level: combination of tissues
• Organ System Level: combination of various organs
• Organisms: Humans with 11 organ systems; reproduction; phenotype influenced by genes and environment
• Population: gene frequencies shaped by evolution; life-history traits

Page 6: Body Composition – Elements and Molecules

• Elements by percentage in the human body (molecular composition):
  • Hydrogen: 62%
  • Oxygen: 26%
  • Carbon: 10%
  • Nitrogen: 1.5%
  • Other elements: 1%
• Major elemental/biomolecule distribution (Molecular composition):
  • Water: 66%
  • Proteins: 20%
  • Lipids: 10%
  • Carbohydrates: 3%
  • Minerals (Calcium, Phosphorus, etc.): ~1%
• Trace elements: silicon, fluorine, copper, manganese, zinc, selenium, cobalt, molybdenum, cadmium, chromium, tin, aluminum, boron
• Note: ©2018 Pearson Education, Inc. for figures on elemental/molecular composition

Page 7: Characteristics of Life

• Responsiveness: adapt to changes via acute or chronic adjustments; homeostasis
• Growth & Differentiation:
  • Hypertrophy: increase in cell size
  • Hyperplasia: increase in cell number
  • Differentiation: cells acquire specialized functions
• Reproduction
• Movement: internal and/or external

Page 8: Metabolism & Excretion – Key Processes

• Metabolism comprises chemical reactions:
  • Anabolism: synthesis of complex molecules
  • Catabolism: breakdown of complex molecules
• Absorption: material uptake into the body
• Respiration: oxygen uptake, transport, and use
• Excretion: elimination of waste, CO2, excess ions

Page 9: Organ Systems and Integration

• FIG. 1.2 Organ Systems overview
• System names with includes and representative functions:
  • Circulatory: Heart, blood vessels, blood; Transport of materials between all cells
  • Digestive: Stomach, intestine, liver, pancreas; Conversion of food into transportable particles; elimination of some wastes
  • Endocrine: Glands; Regulation via regulatory molecules
  • Integumentary: Skin; Protection from environment; barrier and sensing
  • Immune: Lymphoid tissues; Defense against foreign invaders
  • Musculoskeletal: Skeletal muscles, bone; Support and movement
  • Nervous: Brain, spinal cord; Electrical signaling and regulation
  • Respiratory: Lungs, airways; Gas exchange
  • Digestive: already listed above; (included here for integration emphasis)
  • Reproductive: Ovaries, uterus, testes; Perpetuation of species
  • Urinary: Kidneys, bladder; Water and solute balance; waste removal
  • Musculoskeletal (reiteration for emphasis)
• Integration figure: shows how integumentary, respiratory, nervous, digestive, circulatory, endocrine, reproductive, urinary, musculoskeletal systems interrelate; hollow organ interiors are part of external environment in schematic

Page 10: Energy Principles and ATP

• Laws of thermodynamics govern energetics:
  • 1st Law: Energy cannot be created or destroyed; energy changes form
  • 2nd Law: Every energy transformation loses some energy as heat; not all energy is reusable
• Energy values often expressed in Joules: $J = ext{Joules}$
• Adenosine triphosphate (ATP) for short-term energy storage and use by cells
• Catabolism: Substrate + O2 → H2O + CO2 + Heat
• Note: Enzymatic steps and efficiencies affect usable energy; E-values typically in Joules

Page 11: Extracellular & Intracellular Fluid; Mass Balance

• (a) Extracellular fluid (ECF) as a buffer between cells and outside world; cells contain intracellular fluid (ICF); cell membranes separate cells from ECF
• (b) Mass balance in the body (Law of Mass Balance):
  • Mass balance = Existing body load + Intake or metabolic production − Excretion or metabolic removal
• (c) Animal cell in summary (key factors):
  • Input: Intake through intestine, lungs, skin
  • Body load: Existing load
  • Output: Excretion by kidneys, liver, lungs, skin
  • Metabolism: production leading to new substances
• Diagrammatic note of intracellular/extracellular fluid and Na+/K+/Cl− distribution across the cell membrane in steady state

Page 12: Basic Principles – Surface Area, Volume, and Flux

• Heat, water, and ions move along concentration gradients
• Surface area-to-volume (SA:V) ratio influences flux
• Higher SA:V → faster flux; examples:
  • SA:V = 2 → X; SA:V = 1.25 → X; SA:V = 0.27 → X; SA:V = 30 → X (illustrative ratios)
• Concept: small organisms or cell surfaces with greater SA:V flux faster; larger cells have slower flux per unit volume

Page 13: Animal Cell – Summary Parameters

• Extracellular fluid (ECF) and intracellular fluid (ICF) with ion concentrations (example schematic):
  • 140 mmol/L Na+ in ICF/ECF distribution varies by membrane transport
  • 3 Na+ out, 2 K+ in per ATP hydrolysis cycle (Na+/K+-ATPase activity)
  • Equilibrium vs homeostasis: steady-state disequilibrium maintained by active transport
• Na+, Cl−, K+ distribution across cell membrane; ADP/ATP cycling; balance of ions
• Concentration gradients and membrane potential depend on transporter activity and membrane permeability

Page 14: Fick’s Law of Diffusion

• J – rate of diffusion (mol/s)
• A – surface area for diffusion (m^2)
• D – diffusion coefficient (m^2/s)
• ΔC – difference in solute concentration (mol/m^3)
• ΔX – diffusion distance or membrane thickness (m)
• Practical form (approximate):$J \,=\,-D\,A\,\frac{\Delta C}{\Delta X}$

Page 15: Variables Governing Cellular Control

• Key variables (not absolute):
  • Range of environmental factors that affect cells
  • Materials for cell needs
  • Signaling compounds
• Local control: cell or tissue level
• Reflexes: higher-order responses requiring CNS

Page 16: Homeostasis and Control Systems

• Feedback loops modulate response:
  • Negative feedback: homeostatic stabilization of a variable
  • Positive feedback: reinforces changes; not generally homeostatic
• Feedforward control: anticipates changes to maintain stability

Page 17: Biomolecules – Four Major Groups and Basic Functions

• Carbohydrates, Lipids, Proteins, Nucleotides
• Basic functions: energy provision and building blocks for structures and processes

Page 18: Lipids and Energy Storage

• Lipids provide energy storage; fatty acids (FAs) as energy substrate
• Some fatty acids are nutritionally essential
• Structural feature: more unsaturated carbons → more kinked shape; affects membrane fluidity

Page 19: Lipid-Related Molecules and Membrane Structure

• Eicosanoids: modified 20-carbon fatty acids with ring structures; include prostaglandins, thromboxanes, leukotrienes; regulate physiological functions
• Steroids: four-ring structure; examples include cortisol, pregnenolone, aldosterone, testosterone, estradiol
• Phospholipids: glycerol backbone with two fatty acids and a phosphate group; hydrophilic heads and hydrophobic tails; key membrane component
• Cholesterol: essential component influencing membrane fluidity and steroid synthesis
• The phospholipid bilayer arrangement places polar heads toward aqueous environments and nonpolar tails inward

Page 20: Energy Sources and Storage Molecules

• Fatty acids as major energy substrate; acetyl-CoA formation feeds into metabolism
• Glycogen: carbohydrate storage molecule in animals; stored in skeletal muscle and liver in limited amounts
• Lipid storage is favored for energy reserve

Page 21: Amino Acids and Proteins

• 20 amino acids; 9 essential for humans
• Peptides → Proteins (polypeptide chains)
• Roles of proteins:
  • Structural (e.g., collagen, elastin, keratin)
  • Enzymes: catalyze reactions
  • Signaling molecules and receptors
  • Energy source (to a limited extent)

Page 22: Protein Structure

• Secondary structure: hydrogen bonds between backbone segments; α-helix and β-strands (sheets)
• Tertiary structure: three-dimensional folding of a single polypeptide; stabilized by disulfide bonds, ionic bonds, hydrogen bonds, hydrophobic interactions
• Quaternary structure: multiple subunits assembled noncovalently (e.g., hemoglobin)
• Structure determines function; extremes of pH and temperature can denature proteins

Page 23: Protein Denaturation – Temperature and pH Effects

• Temperature and pH changes can disrupt protein structure and function
• Example: a protein denatures around a certain heat threshold; activity declines as structure unfolds

Page 24: Protein Functions and Protein-Ligand Interactions

• Protein homeostatic functions include:
  • Enzymes
  • Membrane transporters
  • Signaling molecules & receptors
  • Binding proteins
  • Immunoglobulins
  • Regulatory proteins
• Key terms:
  • Ligand: binds to another molecule
  • Substrate: ligand that binds to an enzyme or transporter
  • Cofactor: vitamins or other molecules required for activity

Page 25: Enzyme Regulation and Activation

• Proteolytic activation: inactive protein becomes active after peptide fragments are removed
• Allosteric activator: binds away from and increases activity of binding site
• Cofactors: required for active binding site; without them, the protein is inactive
• Competitive inhibitor: blocks ligand binding at the active site
• Allosteric inhibitor: modulates away from binding site to inactivate the site

Page 26: Physiological pH and Buffers

• Physiological pH range: human body typically maintains 7.35 to 7.45; extremes can be life-threatening
• pH definitions:
  • pH = -\log [\mathrm{H^+}] = \log \frac{1}{[\mathrm{H^+}]}
• Acid-base concepts:
  • Acids: [H+] 0 to 6
  • Neutral (water): pH 7
  • Bases: pH 8 to 14
• Buffering: H2O + CO2 ⇌ H2CO3 ⇌ H+ + HCO3− (carbonic acid–bicarbonate buffering system)
• Notable element: trace elements contribute to catalytic and signaling roles

Page 27: Nucleotides, Nucleic Acids, and Gene Expression

• Nucleotides: energy currency and signaling molecules
• Nucleic acids provide information storage and transmission
• Transcription: DNA → RNA (mRNA, tRNA, rRNA)
• Translation: mRNA → protein (amino acid sequence)
• Post-translational modifications regulate protein function
• rRNA forms the core of ribosomes

Page 28: Ions and Polarity

• Cations: Na+, K+, Ca2+, Mg2+; Anions: Cl−, bicarbonate (HCO3−), phosphate (Pi), sulfate
• Nonpolar molecules do not form ions in solution and often require carriers for transport

Page 29: Hydrophilic vs Hydrophobic Interactions and Membrane Formation

• Hydrophilic interactions: polar regions or ionic bonds dissolve in water; hydration shells form around ions; lowers freezing point via hydration effects
• Hydrophobic interactions: nonpolar molecules resist water; phospholipids form bilayers with polar heads outward and nonpolar tails inward, enabling membrane formation
• Membrane bilayer basis for biological membranes and cellular compartments

Page 30: The Cell – Basic Architecture and Compartments

• Cell components: plasma membrane, cytoplasm, nucleus, membranous organelles, cytosol, inclusions
• Membranes provide protection, selective exchange, separation of compartments, and sensing of extracellular stimuli
• Phospholipid bilayer constitutes the fundamental membrane unit
• Pericardial membrane note: tissue surrounding the heart; membranes surround cells and organelles
• Ova, red blood cells, and other cell types have characteristic sizes for scale context

Page 31: Major Organelles and Cellular Architecture

• Organelles listed: Microvilli, free and fixed ribosomes, centriole, centrosome, cytoskeleton, secretory vesicles, mitochondrion, Golgi apparatus, peroxisomes, lysosomes, endoplasmic reticulum (rough and smooth), ribosomes, cytosol, nucleus, nucleoplasm, chromatin, nuclear pores, nucleolus
• Tubular and vesicular trafficking is central to protein processing and transport

Page 32: Plasma Membrane Components and Functions

• Functions:
  • Cell-to-cell communication
  • Structural support and adhesion
  • Regulation of exchange with extracellular fluid
  • Physical barrier
  • Senses extracellular stimuli
• Components:
  • Phospholipids, proteins, glycolipids, sterols
  • Some channel proteins are gated and respond to ligands or stimuli

Page 33: Mitochondria, Peroxisomes, Golgi, Lysosomes, ER, and Nucleus

• Mitochondria: double membrane, cristae; site of ATP synthesis; matrix and intermembrane space
• Peroxisomes: enzymes for fatty acid breakdown and detoxification
• Golgi apparatus: cisternae with vesicles; protein modification and packaging
• Lysosomes: digestive enzymes in vesicles
• Endoplasmic reticulum: Rough ER with ribosomes for protein synthesis; Smooth ER for lipid synthesis and Ca2+ storage
• Centrioles and nucleus: nuclear envelope with pores; nucleolus; chromatin

Page 34: Four Primary Tissue Types

• Epithelial, Connective, Muscular, Neural
• Examples:
  • Connective: fat, bone, blood, lymph, tendons
  • Epithelial: lining and exchange surfaces
  • Muscular: muscle tissues
  • Neural: neurons and glial cells

Page 35: Neural Tissue Components

• Neuroglia: supporting cells; can divide
• Neurons: electrical signal conduction; long cells; cannot reproduce easily
• Dendrites: receive stimuli
• Axons: transmit signals (action potentials)

Page 36: Muscle Types

• Cardiac muscle: myogenic, branched, scar tissue; pumps blood
• Skeletal muscle: multinucleated; attaches to bones; voluntary or reflex; hypertrophy
• Smooth muscle: nonstriated; can replicate (hyperplasia); reflex or myogenic control

Page 37: Glandular Epithelium

• Classified by secretion type and gland structure; modes of secretion
• Exocrine: ducts to epithelial surface or body lumen
• Endocrine: secretions into extracellular fluid then blood/lymph; hormones
• Epithelium as site of exchange with environment

Page 38: Epithelium – Exchange, Transport, Ciliated, Protective, Secretory

• Exchange Epithelium: thin, flat cells; rapid movement across epithelium
• Transporting Epithelium: selective transport between lumen and ECF; tight junctions prevent paracellular movement; substances cross the epithelial cell
• Ciliated Epithelium: cilia create fluid currents
• Protective Epithelium: multilayered, constantly renewing (e.g., skin)
• Secretory Epithelium: mucus secretion (exocrine) and hormone release into blood (endocrine)
• Goblet cells secrete mucus into lumen

Page 39: Energy Use in Cells

• Energy is the capacity to do work
• Chemical work: forming/breaking chemical bonds
• Transport work: moving ions, molecules; creating concentration gradients
• Mechanical work: moving organelles; contracting muscles

Page 40: Free Energy and Enzymes

• Exergonic reactions release energy (products lower energy than reactants)
• Endergonic reactions require energy input (activation energy > products initially)
• Enzymes lower activation energy, increasing reaction rate

Page 41: Types of Enzymatic Reactions

• Phosphorylation: addition of a phosphate group
• Oxidation-reduction (redox): reduced species gain electrons; oxidized lose electrons
• Hydrolysis and dehydration synthesis: water as product in dehydration; water addition in hydrolysis
• Addition-subtraction-exchange reactions: functional groups added/removed/exchanged
• Kinases: add phosphate groups
• Deamination: remove amino group; Amination: add amino group; Transamination: transfer amino group
• Ligation (synthesis): synthases join molecules

Page 42–43: Aerobic and Anaerobic Metabolism of Glucose

• Anaerobic metabolism (glycolysis only):
  • C6H12O6 → 2 C3H5O3− + 2 H+ (pyruvate reduced to lactate in some tissues) + net ATP = 2
• Aerobic metabolism (glycolysis + Citric Acid Cycle + Electron Transport System):
  • 1 glucose + 6 O2 → 6 CO2 + 6 H2O + 30–32 ATP
• Pathway summary:
  • Glycolysis (cytoplasm): 4 ATP produced, net 2 ATP; 2 NADH produced
  • Pyruvate to Acetyl-CoA (mitochondria): produces NADH
  • Citric acid cycle (mitochondria): produces NADH, FADH2, GTP (or ATP)
  • Electron transport system (mitochondria): oxidative phosphorylation yields the bulk of ATP
• ATP yield caveat: Cytoplasmic NADH from glycolysis may yield ~2.5 ATP/NADH when shuttled into mitochondria, or ~1.5 ATP/NADH in some shuttles (e.g., glycerol phosphate shuttle)
• Key equations:
  • Glycolysis net: $\text{Glucose} + 2\,\mathrm{NAD^+} + 2\,\mathrm{ADP} + 2\,\mathrm{P<em>i} \rightarrow 2\,\mathrm{Pyruvate} + 2\,\mathrm{NADH} + 2\,\mathrm{ATP} + 2\,\mathrm{H</em>2O} + 2\,\mathrm{H^+}$
  • Aerobic glucose oxidation (overall): $\mathrm{C<em>6H</em>{12}O<em>6} + 6\, \mathrm{O</em>2} \rightarrow 6\, \mathrm{CO<em>2} + 6\, \mathrm{H</em>2O} + \text{ATP (30-32)}$
• Pyruvate is the branch point between aerobic and anaerobic metabolism (see Page 48 for details)
• Citric acid cycle and ETC details summarized on the navigator diagrams (GTP/ATP yields, NADH, FADH2 totals)

Page 44: Amino Acids – Metabolism and Interconversions

• Amino acids listed: Alanine, Cysteine, Glycine, Serine, Threonine, Tryptophan, etc.
• Pathways:
  • Pyruvate can be converted to lactate or feed into Acetyl-CoA
  • Other amino acids feed into citric acid cycle intermediates: OAA, α-KG, citrate, isocitrate, succinyl-CoA, fumarate, malate
• Some amino acids convert to glycerol or fatty acids for energy/storage pathways
• Gluconeogenesis and energy production can reuse amino acids for ATP generation

Page 45–46: Oxidative Phosphorylation and Proton Motive Force

• Mitochondrion structure and the electron transport chain create a proton gradient across the inner membrane
• Proton motive force drives ATP synthesis via ATP synthase
• Steps:
  1) NADH and FADH2 donate electrons and protons to the ETS
  2) Electron flow pumps protons into the intermembrane space; gradient forms
  3) Electrons end at O2 to form water; NAD+ and FAD are regenerated
  4) Protons flow back through ATP synthase to phosphorylate ADP to ATP
  5) A portion of energy is released as heat
• ATP synthase: roughly 3 H+ translocated per ATP synthesized (empirical value varies with organism and conditions)

Page 46–48: Pyruvate Branching and Lactate Shuttles

• When oxygen becomes available again after anaerobic metabolism, lactate and pyruvate can be converted back to glucose or supplied to the mitochondria for oxidation
• Lactate dehydrogenase converts pyruvate to lactate (and back) as part of the anaerobic–aerobic transition
• Some tissues use lactate as a gluconeogenic precursor or fuel source in oxidative metabolism

Page 49: Gene Expression

• Gene concepts:
  • Gene: region of DNA transcribed into RNA; some genes are constitutively active; others are regulated (induced or repressed)
• Transcription: DNA → RNA (mRNA, tRNA, rRNA)
• Translation: mRNA → protein (assembly of amino acids into polypeptide chain)
• Post-translational modifications alter protein function
• rRNA is a core component of ribosomes

Page 50–51: Fluid Compartments and Homeostasis

• Two main fluid compartments: Cells (ICF) and Extracellular Fluid (ECF)
• Osmotic equilibrium vs chemical and electrical disequilibrium
• Homeostasis is not the same as equilibrium (except for water)

Page 51–53: Diffusion and Osmosis Fundamentals

• Diffusion basics: movement of solutes from high to low concentration
• Diffusion stops when AC = 0 (chemical potential balance)
• Osmosis: diffusion of water across membranes via aquaporins; osmolarity vs tonicity concepts
• Osmolarity: osmotically active solutes per liter of solution (mOsM/L)
• Osmolality: osmotically active solutes per kilogram of solvent (mOsM/kg)
• Isosmotic, Hyposmotic, Hyperosmotic definitions based on solute activity and membrane permeability

Page 54–55: Extracellular and Interstitial Fluid; Volume Regulation

• Intracellular fluid (ICF): within cells
• Extracellular fluid (ECF): outside cells; includes interstitial fluid and blood plasma
• Blood plasma is the extracellular fluid inside vessels; interstitial fluid bathes most cells
• Body water distribution and compartmentalization

Page 56–57: Osmotic Stress and Tonicity

• Hypotonic solutions can cause cells to swell and potentially lyse if solute removal is slow
• Cells cannot actively pump water; they regulate water permeability and solute concentrations to maintain volume
• Osmolarity is not tonicity; tonicity depends on solute permeability (penetrating vs nonpenetrating solutes)
• Example relationships: Hyperosmotic, Isosmotic, Hyposmotic relative to cell interior

Page 58–59: Membrane Proteins and Transporters

• Channel proteins create water-filled pores; gating mechanisms control opening
• Membrane proteins are categorized by structure (integral vs peripheral) and function (transporters, channels, receptors, enzymes, cytoskeleton links, cell adhesion)
• Gated channels include mechanically gated, voltage-gated, chemically gated channels
• Receptors can trigger intracellular signaling upon ligand binding

Page 60–63: Membrane Transport – Diffusion, Osmosis, and Active Transport

• Membrane transport types:
  • Diffusion (simple and facilitated)
  • Osmosis (water movement via aquaporins)
  • Facilitated diffusion (carrier proteins like GLUT transporters for glucose)
  • Active transport (uses ATP to move solutes against gradients)
• Primary active transport uses ATP directly (e.g., Na+/K+-ATPase; antiporters and symporters)
• Secondary active transport uses ion gradients to drive transport of other solutes (e.g., Na+-glucose symporter; indirect energy source via Na+ gradient)
• Na+-K+-ATPase pumps 3 Na+ out and 2 K+ in per ATP hydrolyzed, helping maintain ionic gradients and resting potential
• Epithelial transport concepts:
  • Apical (luminal) vs basolateral membranes
  • Transcellular (through cells) vs paracellular (between cells) transport
  • Tight junctions regulate paracellular movement
• Absorption vs secretion across epithelia; transcytosis and caveolae-mediated pathways
• Primary and secondary active transport examples are illustrated (e.g., glucose uptake in intestine and kidney tubules)

Page 64–65: Endocytosis, Exocytosis, and Vesicular Transport

• Endocytosis processes:
  • Phagocytosis: engulfment of large particles; phagosome fuses with lysosome
  • Pinocytosis: non-specific uptake of extracellular fluid with solutes
  • Receptor-mediated endocytosis: specific uptake via receptor-coated pits; receptors recycled via vesicles
• Exocytosis: release of vesicle contents via SNARE complex (v-SNAREs on vesicles and t-SNAREs on plasma membrane)
• Vesicular trafficking includes endosomes and lysosomes; membrane components recycled through exocytosis
• All these processes require ATP

Page 65–66: Transcellular Transport and Epithelial Polarity

• Transepithelial transport includes absorption and secretion across polarized epithelia
• Caveolae and vesicular transport contributions to transcytosis and protein trafficking
• Membrane specialization with apical and basolateral domains enables directional transport

Page 66–69: Resting Membrane Potential and Ion Gradients

• Resting membrane potential (Em) around -70 mV in typical cells
• Em arises from:
  • Selective membrane permeability to ions
  • Electrogenic Na+/K+-ATPase pumps
  • Donnan equilibrium (intracellular proteins contribute to charge balance)
• Nernst equation (for a single ion):$E<em>m = \frac{RT}{zF} \ln \left(\frac{[X^+]</em>o}{[X^+]_i}\right)$
• Goldman-Hodgkin-Katz equation provides membrane potential considering multiple ions and their permeabilities
• Em is typically stable but can vary; excitability arises with transient changes (graded potentials) leading to action potentials in excitable cells

Page 70–71: Signaling and Communication Modalities

• Acute membrane potential changes (APs) occur in excitable cells (muscle, neurons, fertilized eggs, some endocrine cells)
• Direct cell signaling: autocrine, paracrine, endocrine, neural, neuroendocrine
• Hormones vs cytokines:
  • Hormones: secreted by endocrine glands/cells; can act at distant targets via blood
  • Cytokines: peptides released by many cells; act locally (autocrine and paracrine)
• Neuroendocrine signaling: neurons releasing neurohormones into the blood for distant targets
• Lipophilic signals diffuse through membranes and bind intracellular or nuclear receptors; lipophobic signals bind membrane receptors

Page 72–74: Long-Distance Signaling and Signal Types

• Long-distance signaling pathways include electrical signals (neurons) and chemical signals (hormones)
• Endocrine signaling: hormones into blood; target cells with receptors respond
• Neurotransmitters: chemicals released by neurons to diffusing across synapses to adjacent cells
• Neurohormones: neurosecretory signals released into the blood for distant targets
• Receptors and signal specificity

Page 75–79: Signal Transduction Pathways

• Basic signal transduction model:
  • Signal molecule binds to membrane receptor (first messenger) → transducer → second messengers → kinases and other effectors → cellular response
• GPCR pathways (two examples):
  • GPCR-Adenylyl Cyclase pathway:
    1) Signal binds receptor → activates G protein
    2) G protein activates adenylyl cyclase
    3) Adenylyl cyclase converts ATP to cyclic AMP (cAMP)
    4) cAMP activates protein kinase A (PKA)
    5) PKA phosphorylates target proteins → cellular response
  • Chemical diagram highlights ATP, cAMP, Ca2+ as signaling players
  • GPCR-Phospholipase C (PLC) pathway:
    1) Signal binds receptor → activates G protein
    2) G protein activates PLC
    3) PLC cleaves membrane phospholipids into DAG and IP3
    4) IP3 triggers Ca2+ release from ER; DAG activates PKC
    5) PKC phosphorylates target proteins → cellular response
• Ionotropic vs metabotropic signaling:
  • Ionotropic: ligand directly gates ion channels
  • Metabotropic: receptor activation triggers chemical cascade impacting ion channels later
• Signaling components and consequences include cytoskeletal changes, gene activity modulation, and enzyme activity changes
• Receptor specificity, saturation, and competition; agonists and antagonists; receptor up- and down-regulation; termination of signaling

Page 80–81: Control of Signaling and Regulation

• Tonic control: constant regulation (dimmer switch) with continuous signal
• Antagonistic control: opposing systems modulate outcomes (toggle switch)

Page 82–83: Reflexes and Sensory Receptors

• Reflex arc: sensory receptor → afferent neuron → integrating center (IC) → efferent neuron → effector organ
• Types of reflexes:
  • Somatic reflex: skeletal muscle effector
  • Visceral reflex: smooth muscle, cardiac muscle, glands, adipose tissue
• Receptors can be:
  • Central (CNS) receptors: located in brain/spinal cord
  • Peripheral (PNS) receptors: outside CNS
• Sensory receptors classifications:
  • Special sense receptors: smell, taste, vision, balance, hearing
  • Visceral (internal) receptors: monitor cardiovascular, respiratory, digestive, urinary, and reproductive systems
  • Somatic receptors: monitor body position, skin sensations (touch, pain, temperature, etc.)
• Central receptors vs peripheral receptors; sensory modalities and pathways

Page 84–85: Receptor Organization and Autonomic Regulation

• Various signaling patterns and reflex examples:
  • Receptor → integrating center → efferent pathway → effector → response (neural, endocrine, or neuroendocrine pathways)
• Neuroendocrine examples include rapid signaling in certain reflexes and hormone release patterns
• Autonomic nervous system (ANS) anatomy (illustrative):
  • Sympathetic division: ‘Fight or Flight’; originates in thoracic and lumbar regions; collateral ganglia; effects on eyes, heart, lungs, digestive organs, liver, kidney, bladder, etc.
  • Parasympathetic division: ‘Rest and Digest’; craniosacral origins (e.g., vagus nerve X); effects on glands, heart, lungs, digestive tract, urinary, reproductive organs
• Interaction between parasympathetic and sympathetic systems underlies homeostatic regulation of organ function