Human Physiology PDF

Module 1: Levels of Organization Definition of Physiology ​ Physiology = molecules → cells → tissues → organs → organ systems → organisms → populations of one species Life Processes 1.​ Require energy 2.​ Respond to stimuli 3.​ Grow 4.​ Reproduce 5.​ Maintain hom...

Module 1: Levels of Organization Definition of Physiology ​ Physiology = molecules → cells → tissues → organs → organ systems → organisms → populations of one species Life Processes 1.​ Require energy 2.​ Respond to stimuli 3.​ Grow 4.​ Reproduce 5.​ Maintain homeostasis Key Themes ​ Structure/function relationships ​ Compartmentation (Molecular interactions, mechanical properties of cells, tissues, and organs) ​ Biological energy use (Living organisms need energy to grow) ​ Communication (Information flow coordinates body functions) ​ Homeostasis & Control Systems (Maintains internal stability) Homeostasis ​ The body's ability to maintain a stable internal environment ​ Monitored by critical variables: O₂, CO₂, HR, RR, BG (within a range of values) ​ Failure to maintain homeostasis leads to disease/pathology Homeostasis Equilibrium: ​ Plasma-dynamic steady state: Materials move between ICF (intracellular fluid) & ECF (extracellular fluid) ​ Example: K⁺ is high in ICF, Na⁺ is high in ECF Control Systems ​ Local systems & response loops regulate homeostasis ​ Regulation from local to long-distance: 1.​ Input signal (cell signaling—can be systemic or localized) 2.​ Integrating Center (control center: negative feedback for homeostatic stabilization)  3.​ Output signal Types of Feedback Loops: ​ Negative feedback loop (homeostatic & stabilizing) ​ Positive feedback loop (e.g., labor, blood clotting) ​ Feed-forward response (anticipates homeostasis disruption) Example of a Control System 1.​ Stimulus: Water temperature drops below setpoint 2.​ Sensor: Thermometer detects temperature change 3.​ Input signal: Signal sent from sensor to control box via wire 4.​ Integrating Center: Control box responds to temperature change 5.​ Output signal: Signal sent through wire to the heater 6.​ Target: Heater turns on to restore temperature Causes of Disease 1.​ Internal Causes ○​ Abnormal cell growth (e.g., cancer) ○​ Production of self-antibodies (autoimmune diseases) ○​ Cell process failure or death 2.​ External Causes ○​ Physical trauma ○​ Toxic chemical exposure ○​ Foreign pathogens Body’s Internal Environment ​ ECF (extracellular fluid) = Fluid that surrounds cells ​ ICF (intracellular fluid) = Fluid inside cells ​ Buffer zone: ECF serves as a buffer between external environment and ICF ​ Transition zone: Adapts to keep ICF stable when external conditions change Set Point ​ Definition: Optimum value for a regulated variable ​ Example: Body temperature = 98.6°F ​ Biological/Circadian rhythms: Regular fluctuations around critical values in the body ​ Acclimation: Lab-controlled environmental adaptation ​ Acclimatization: Natural environmental adaptation Module 2: Compartmentation, Cells, and Tissues Membranes and Compartments ​ Compartments are separated by membranes ​ Cell membrane = Plasmalemma (Phospholipid bilayer) ○​ Hydrophobic tails (inside) ○​ Hydrophilic heads (outside) ​ Cell membrane is studded with proteins (glycoproteins, glycolipids) ​ Glycocalyx: Protective outer coating of the membrane Main Functions of Cell Membrane 1.​ Physical Isolation: Separates ICF from ECF 2.​ Regulation of Exchange: Controls entry/exit of nutrients, ions, waste products 3.​ Communication: Membrane proteins recognize/respond to external signals 4.​ Structural Support: Cytoskeleton provides shape & stability Fluid Mosaic Model ​ Glycocalyx: Outer membrane coating (cell protection) ​ Cell membrane contains lipids, proteins, carbs, cholesterol ​ Cholesterol waterproofs membrane and makes it flexible Intracellular Components 1.​ Cytoplasm: Space inside the cell, surrounded by the cell membrane ○​ Cytosol: Fluid portion of the cytoplasm ○​ Inclusions: Non-membrane-bound materials (e.g., nutrient granules, lipid droplets) 2.​ Protein Fibers: ○​ Microfilaments (e.g., actin) ○​ Intermediate filaments (e.g., keratin) ○​ Microtubules (e.g., centrioles, cilia, flagella) Functions of the Cytoskeleton 1.​ Cell shape 2.​ Internal organization 3.​ Intracellular transport 4.​ Assembly of cells into tissues 5.​ Movement (e.g., motor proteins like myosin, kinesins, dyneins) Organelles ​ Mitochondria: Powerhouse of the cell (ATP production) ​ Rough ER: Contains ribosomes → Protein synthesis ​ Smooth ER: Lipid, fatty acid, and steroid synthesis ​ Golgi Apparatus: Sorts, modifies, packages proteins into vesicles ​ Vesicles: Small sacs (e.g., lysosomes, peroxisomes) ​ Lysosomes: Break down old cell material/pathogens (failure can lead to rheumatoid arthritis) ​ Nucleus: Control center, contains DNA ○​ Nuclear envelope (2 membranes) ○​ Nuclear pore complexes (Allow controlled communication with the cytoplasm) ○​ Nucleoli (Direct ribosomal RNA synthesis) Types of Tissues ​ Cell junctions form tissues via cell adhesion molecules (CAMs) ​ Types of junctions: ○​ Gap junctions: Communication ○​ Tight junctions: Selective permeability (e.g., kidneys) ○​ Anchoring junctions: Strength & stability 1) Epithelial Tissue (Protection & Exchange) ​ Covers internal environment & regulates material exchange ​ Basal lamina: Anchors epithelium in place ​ Types: ○​ Exchange epithelia (Simple squamous, gas exchange in lungs/blood vessels) ○​ Ciliated epithelia (Moves fluids/particles, found in respiratory tract) ○​ Protective epithelia (Resist stress, e.g., epidermis) ○​ Secretory epithelia (Sweat, mucus, endocrine glands) ○​ Transporting epithelia (Selective transport, mitochondria-rich) 2) Connective Tissue (Support & Barriers) ​ Characterized by extensive extracellular matrix ​ Types: 1.​ Loose connective tissue (Elastic, found under skin) 2.​ Dense connective tissue (Tendons, ligaments) 3.​ Supporting connective tissue (Cartilage, bone) 4.​ Adipose tissue (Fat—white vs. brown) 5.​ Blood (Fluid connective tissue) 3) Muscle Tissue (Contraction for Movement) ​ Types: ○​ Skeletal muscle ○​ Cardiac muscle ○​ Smooth muscle 4) Neural Tissue (Excitable, Sends Signals) ​ Neurons: Transmit electrical signals ​ Glial cells (neuroglia): Support and protect neurons Tissue Remodeling ​ Plasticity: The ability of a cell to specialize into a different type from its original purpose ​ Necrosis: Cell death due to trauma, toxins, or lack of oxygen ​ Apoptosis: Programmed (intentional) cell death, beneficial for proper development and maintenance ​ Stem Cells: ○​ Totipotent: Can become any type of cell in the human body ○​ Pluripotent: Can become most cells but not all ○​ Multipotent: Can specialize into one type of tissue Module 5: Membrane Dynamics Osmosis ​ Humans are ~60% water ○​ ⅔ of total water is intracellular fluid (ICF) ○​ ⅓ is extracellular fluid (ECF) ​ Osmosis: Movement of water across a membrane due to a concentration gradient of solutes ○​ Water moves toward the higher solute concentration ○​ Osmotic equilibrium is reached when solute concentrations are equal on both sides ○​ Osmotic pressure: The force required to oppose osmotic movement ○​ Water naturally wants to move across membranes to balance concentration differences Osmolarity & Osmolality ​ Osmolarity: Number of osmotically active particles per liter of solution  ​ Osmolality: Number of osmotically active particles per kilogram of water ​ Typical human body osmolarity: 280-296 milliosmoles (mOsM) Tonicity ​ Tonicity: Describes how a solution affects cell volume based on water movement ○​ Hypertonic solution: Water moves out of the cell → Cell shrinks ○​ Isotonic solution: No net water movement → Cell stays the same size ○​ Hypotonic solution: Water moves into the cell → Cell swells ​ Osmolarity alone cannot predict tonicity because it also depends on solute permeability ○​ Penetrating solutes: Can cross the membrane (e.g., urea) ○​ Non-penetrating solutes: Cannot cross (e.g., NaCl) Transport Processes 1) Bulk Flow ​ Most general form of transport ​ Movement of gases and liquids from high to low pressure ​ Examples: ○​ Respiration (air moving in and out of lungs) ○​ Blood flow (arteries → veins) 2) Selective Permeability of Cell Membranes ​ Passive Transport (No energy required) ○​ Simple diffusion (Movement down a concentration gradient) ​ Active Transport (Requires energy - ATP) ○​ Moves substances against the concentration gradient (low → high) 3) Diffusion ​ Passive process (no energy required) ​ Moves from high to low concentration ​ Does NOT apply to ions (because they rely on electrochemical gradients) ​ Influencing Factors: ○​ Faster over short distances ○​ Affected by electrical and chemical gradients ○​ Faster at higher temperatures ○​ Slower for larger/heavier molecules ​ Fick’s Law of Diffusion: ○​ Diffusion is proportional to:  1.​ Surface area of the membrane 2.​ Concentration gradient 3.​ Membrane permeability (Depends on lipid solubility, molecular size, and membrane composition) Protein-Mediated Transport ​ For molecules that are too large or lipophobic to cross the membrane directly ​ Types of Transport: 1.​ Facilitated Diffusion: Uses carrier proteins, passive (moves down concentration gradient) 2.​ Active Transport: Uses carrier proteins, requires energy (ATP) (moves against concentration gradient) 4 Major Functions of Membrane Proteins 1.​ Structural Proteins: ○​ Create cell junctions ○​ Connect membrane to cytoskeleton for cell shape 2.​ Membrane Enzymes: ○​ Catalyze chemical reactions on the inner/outer membrane 3.​ Membrane Receptor Proteins: ○​ Facilitate cell signaling & communication 4.​ Membrane Transport Proteins: ○​ Channel Proteins (Allow small molecules to pass) ​ Aquaporins (Water channels) ​ Ion channels ​ Leak channels (always open) ​ Gated channels (open/close due to stimuli) ​ Chemically gated (Ligand-binding) ​ Voltage-gated (Electrical charge changes) ​ Mechanically gated (Pressure, stretch) ​ Carrier Proteins (Slower than channel proteins) ○​ Uniport: Transports one type of molecule ○​ Co-transporters: Transport multiple molecules at the same time ​ Symport: Same direction ​ Antiport: Opposite directions ​ Examples: ○​ GLUT (glucose transport) → Facilitated diffusion ○​ Na⁺/K⁺ ATPase pump → Active transport Vesicular Transport ​ Used for large molecules that cannot pass through membrane proteins 1.​ Phagocytosis ("cell eating") ○​ Engulfs large particles (e.g., bacteria) ○​ Forms a phagosome that merges with lysosomes to digest contents 2.​ Endocytosis ("cell intake") ○​ Engulfs extracellular material into the cell ○​ Types: ​ Pinocytosis ("cell drinking") – Non-selective intake of extracellular fluid ​ Receptor-mediated endocytosis – Specific uptake via receptors ​ Caveolae-mediated endocytosis – Involves lipid rafts (linked to muscular dystrophy) 3.​ Exocytosis ("cell export") ○​ Removes large waste products ○​ Example: Removing low-density lipoproteins (LDL, "bad cholesterol") from the bloodstream ○​ If LDL removal fails → Atherosclerosis (plaque buildup in arteries) Epithelial Transport ​ Transport of substances across epithelial layers 1.​ Two membrane barriers: ○​ Apical membrane (faces the lumen) ○​ Basolateral membrane (faces ECF) 2.​ Absorption vs. Secretion ○​ Absorption: Movement from lumen → ECF (e.g., intestine absorbing nutrients) ○​ Secretion: Movement from ECF → Lumen (e.g., salivary glands releasing saliva) 3.​ Paracellular vs. Transcellular Transport ○​ Paracellular transport: Between epithelial cells ○​ Transcellular transport: Through the epithelial cell (crosses two membranes) 4.​ Transcytosis (Combination of endocytosis & exocytosis) ○​ Allows large molecules to cross epithelial barriers while staying intact Resting Membrane Potential (RMP) ​ RMP ≈ -70 mV (inside of cell is negative relative to outside) ​ Nernst Equation: Used to calculate equilibrium potential for ions ​ Key Features of RMP: 1.​ Electrical disequilibrium (Inside of the cell is more negative) 2.​ Cell membrane is 40% more permeable to potassium (K⁺)  3.​ Changes in membrane permeability alter RMP: ​ Depolarization: Becomes less negative ​ Repolarization: Returns to resting state ​ Hyperpolarization: Becomes more negative than RMP Example: Cystic Fibrosis ​ Cause: Malfunction of CFTR transporter ​ What Happens? 1.​ Cl⁻ ions cannot exit cells properly 2.​ Na⁺ ions follow Cl⁻ imbalance 3.​ H₂O leaves the cell → Thickens mucus 4.​ Results in difficulty clearing mucus in the lungs Module 6: Communication, Integration, and Homeostasis Topic 1: Cell-to-Cell Communication Types of Cell Communication 1.​ Electrical Signals: Changes in membrane potential 2.​ Chemical Signals: Ligands (molecules that bind to receptors) Four Ways Cells Communicate 1.​ Gap junctions: Create cytoplasmic bridges between cells 2.​ Contact-dependent signals: Require direct cell-to-cell contact 3.​ Local chemical signaling: Molecules diffuse through extracellular fluid (ECF) to nearby cells 4.​ Long-distance signaling: Uses chemical and electrical signals (e.g., nervous and endocrine systems) Local Communication ​ Gap junctions: Use connexin proteins to form a connexon channel ​ Allows cells to act as a syncytium (a group of cells functioning as one unit) ○​ Example: Cardiac muscle (heart cells contract together) ​ Paracrine signaling: Chemical signals between neighboring cells ​ Autocrine signaling: A cell releases a signal to itself Long-Distance Communication  ​ Endocrine System: Uses hormones (chemical signals) transported through the bloodstream ​ Nervous System: Uses neurocrines (chemical signals released by neurons) ○​ Neurotransmitters: Fast-acting, cross synapses ○​ Neuromodulators: Slower, act as auto/paracrine signals ○​ Neurohormones: Enter the bloodstream and affect multiple organs Cytokines (Regulatory Peptides) ​ Act like hormones but have broader effects ​ Differences from hormones: 1.​ Cytokines affect a wider range of cells than hormones 2.​ Cytokines are produced by all nucleated cells, while hormones are made by specific glands 3.​ Cytokines are made on demand, while hormones can be stored Topic 2: Signal Pathways Signal Pathway Components 1.​ Chemical signal (First Messenger): A ligand that binds to a receptor 2.​ Receptor activation: Triggers an intracellular response 3.​ Intracellular signal molecules: Activated in response to the receptor 4.​ Response: Modification of proteins or synthesis of new ones Signal Transduction ​ Process of converting an external signal into an internal cellular response ​ Amplification: One signal molecule activates multiple second messengers (cascade effect) Types of Membrane Receptors 1.​ Ligand-Gated Ion Channels (Chemically Gated Channels) ○​ Ligand binding opens/closes an ion channel ○​ Example: Acetylcholine (ACh) binding → Na⁺ influx → muscle contraction 2.​ G-Protein Coupled Receptors (GPCRs) ○​ Most common receptor type ○​ Ligand binding activates a G-protein, which can: 1.​ Open ion channels 2.​ Alter enzyme activity inside the cell  ○​ Example: GPCR activates cAMP (second messenger) → Activates Protein Kinase A (PKA) → Modifies proteins 3.​ Receptor-Enzymes ○​ Ligand binding activates an intracellular enzyme ○​ Examples: 1.​ Tyrosine Kinase: Phosphorylates proteins to alter responses 2.​ Guanylyl Cyclase: Produces cyclic GMP (cGMP) to amplify responses 4.​ Integrins ○​ Receptors that bind to the extracellular matrix (ECM) and cytoskeleton ○​ Can: 1.​ Activate intracellular enzymes 2.​ Change cytoskeleton structure ○​ Example: Blood clotting, wound healing, immune response Topic 3: Novel Signal Molecules These molecules play a role in cell signaling and physiological responses. 1.​ Calcium (Ca²⁺) ○​ Stored in the endoplasmic reticulum (ER) ○​ Binds to calmodulin to alter enzyme activity ○​ Found in all cells 2.​ Nitric Oxide (NO) ○​ Produced by endothelial cells ○​ Causes vasodilation (widens blood vessels) 3.​ Eicosanoids (Lipid-derived signals) ○​ Made from arachidonic acid ○​ Act through G-protein coupled receptors (GPCRs) ○​ Play a role in the immune response 4.​ Leukotrienes ○​ Lipid-derived paracrine signals ○​ Involved in asthma and anaphylaxis 5.​ Prostanoids (Prostaglandins & Thromboxanes) ○​ Produced by the COX enzyme ○​ Regulate sleep, pain, fever, and inflammation ○​ Example: Anti-inflammatory drugs (NSAIDs) inhibit COX to reduce pain and inflammation Topic 4: Modulation of Signal Pathways  ​ The receptor, NOT the ligand, determines the response ​ A receptor can bind multiple ligands (competition) ​ One ligand can have different effects in different tissues Modulation Mechanisms 1.​ Specificity: A receptor only binds to a specific ligand 2.​ Saturation: When all receptors are occupied, the response cannot increase further 3.​ Competition: Some ligands have a higher binding affinity than others Types of Ligands ​ Agonists: Bind to the receptor and activate a response ​ Antagonists: Bind to the receptor and block a response Example: Epinephrine’s Effects on Different Receptors ​ α-receptors: Cause vasoconstriction (narrowing of blood vessels) ​ β-receptors: Cause vasodilation (widening of blood vessels) Receptor Regulation ​ Up-Regulation: Increase in receptor numbers when a ligand is scarce ​ Down-Regulation: Decrease in receptor numbers when a ligand is too abundant Signal Termination ​ To stop a signal, the ligand must be removed 1.​ Ligand is degraded or removed from circulation 2.​ The receptor-ligand complex is internalized (endocytosis) Topic 5: Homeostatic Reflex Pathways Canon’s Four Postulates 1.​ The nervous system regulates the internal environment to maintain homeostasis 2.​ Tonic control: Signals can be increased or decreased (not just on/off) 3.​ Antagonistic control: Different signals have opposing effects 4.​ One chemical signal can have different effects in different tissues ○​ Example: Epinephrine causes vasoconstriction in some tissues and vasodilation in others Homeostatic Reflex Components 1.​ Stimulus → Detected by a sensor (Afferent signal → Approaching control center) 2.​ Integration Center → Processes information (Brain or endocrine gland) 3.​ Response → Sent to target tissue (Efferent signal → Exiting control center) Neural vs. Endocrine Pathways Feature Neural Pathways Endocrine Pathways Signal Electrical + Chemical (Neurotransmitters) Chemical (Hormones) Type Specificity One neuron targets one specific cell Hormones are systemic Speed Very fast Slower Duration Short-term Longer-lasting Intensity Increased firing frequency Increased hormone release