Physiology 2130A First Semester PDF

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1         Physiology 2130  Seth Kadish  2 Module 1: Introduction to Physiology Physiology ● physiology​ → study of function in living organisms ○ explores mechanisms which organism maintain internal environment ○ explain physical, chemical factors for normal function an...

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    Physiology 2130 Seth Kadish

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Module 1: Introduction to Physiology Physiology ● physiology → study of function in living organisms ○ explores mechanisms which organism maintain internal environment ○ explain physical, chemical factors for normal function and disease development ● internal environment: blood, organs, extracellular fluid; interstitial fluid and blood plasma ● external environment: region contiguous with external environment; digestive, respiratory systems ● homeostasis → maintenance of relatively stable conditions within internal environment Feedback control systems ● Positive Feedback (PFCS; feedforward): works to stimulate or amplify controlled variable ● Negative Feedback (NFCS): works to negate controlled variable ■ set point, control center (integrator), effector, controlled variable, and sensor (receptor) ○ essentially controlled variable (detected by sensor) shuts off its own production by effector △ e.g. NFCS works maintain body temperature at 37 C ⬠ if temperature drops below, organs generate heat by shivering and reducing blood flow ⬠ if temperature rises above, organs signal sweat glands to cool down skin layer ● all bodily systems use PFCS and NFCS to maintain homeostasis △ nervous system is useful for rapid communication through network of neurons and nerves △ endocrine system responds more slowly, communicating through release of hormones in blood Levels of organization in human body ● Atom → Molecule → Macromolecule → Organelle → Cell → Tissue → Organs → System → Organism ● cells form specialized structures (tissues) that employ distinct functional cell types △ heart cells form muscle tissue, forms heart tissue and blood vessels → circulatory system Homeostasis ● human body functions to maintain relatively stable conditions ○ i.e. body temperature, water balance, salt concentrations, etc. ● bodily systems detect changes, respond using FCS

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Module 2: Bodily Fluids Fluid Compartments ● intracellular (ICF) and extracellular (ECF) fluid compartment ○ ICF → 67% tbw ○ ECF → 26.4 % interstitial tbw, 6.6% plasma tbw ● ECF: a. interstitial fluid compartment (fluid directly outside cells) b. plasma (watery portion of blood) Plasma ● colloidal solution (e.g. suspended, non-settling substances) ● 92% water and 8% other (i.e. proteins, ions, nutrients, gases, waste products) ● plasma volume remains static, as digestive tract absorption matches loss Chemical Composition ● differences in chemical composition accounted for by cell membrane ○ selectively- permeable barrier formed between ICF and ECF ○ channels and pores regulate passage of molecules across membrane ● body = 60% water ○ compartments allow for gradients to establish (e.g. along cell membrane); help drive certain processes (i.e. K+ pump)

Module 3: Cells Organelles ● Golgi body: packaging proteins from RER into membrane-bound vesicles a. secretory vesicles: transport proteins to cell membrane for release into ECF b. storage vesicles: keep contents remaining in cell ● free ribosomes: dense units of rRNA and protein; translates mRNA into polypeptide chains (building blocks of proteins) ● lysosome: storage vesicles ACTS to digest cellular components (i.e. damaged organelles, invasive bacteria, etc.) ● mitochondrion: production of ATP (energy source) via oxidative phosphorylation; contains own set of DNA helps reproduce without regard for mitotic stages ● endoplasmic reticulum: continuation of nuclear membrane, used to synthesize, store, and transport proteins and lipid molecules a. RER: proteins synthesis, b. SER: lipid/fatty acid synthesis ● cell membrane: selectively permeable membrane regulates substances into and out of cell; detects chemical signals and physical changes in adjacent cells ● centriole: cylindrical bundles of microtubules; assists motion of DNA strand during cell division ● nucleolus: dense body within nucleus containing DNA that produces ribosomal RNA Cell Membrane ● composed of lipid bilayer, proteins, carbohydrates, cholesterol ○ allows selected substances to pass through ● phospholipid bilayer ○ hydrophilic (polar) phosphate heads aligned outside ■ facilitate entry to fat-soluble substances (i.e. oxygen, carbon dioxide, steroid hormones) ○ hydrophobic (non-polar) lipid tail aligned inside ■ major barrier to water-soluble substances (e.g. ions, glucose, urea, etc.) ○ cholesterol maintains fluidity at temperature extremes ■ assists in impermeability to water

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○ ○

enzymes catalyze reactions immediately inside or outside membrane carbohydrates form glycocalyx layer ■ help with cell recognition and immune response Membrane Protein ● Functions: 1. cell reception of chemical hormones and neurotransmitters 2. enzymatic catalysis of metabolic processes 3. ion channels or pores transport for water-soluble substances 4. membrane-transport carriers (e.g. gated channels) 5. cell-identity markers (e.g. antigens, glycoproteins) ● Transport: a. endocytosis/exocytosis (and pinocytosis) ○ larger molecules can be engulfed; ATP-dependent b. lipid bilayer diffusion (for fat soluble molecules) c. protein-channel facilitated diffusion (for water-soluble molecules) ○ solute entry along electrochemical gradient; limited number of channels d. active transport ○ pumps molecules against electrochemical gradient Diffusion ● passive molecular movement [H] to [L] ○ down chemical gradient electrically-charged molecules tend toward opposite charge (e.g. X+ moves toward - region) ○ down electrical gradient ✓ if chemical and electrical gradient oppose each other, net movement balance of two ○ (i.e. electrochemical gradient) Diffusion Factors i. protein channels size (e.g. glucose cannot fit) ii. molecular charge (e.g. X+ cannot go through + channel) iii. electrochemical gradient (e.g. > gradient, > movement) iv. number of membrane channels (e.g. > channels, > # ions diffusion) Facilitated Diffusion ● some water-soluble substances alter protein’s shape to open diffusion pathway (e.g. keycard entry) ○ energy neutral; powered by electrochemical gradient ● limitations exist based on number of protein channels ○ [H] can saturate channels, dampen diffusion ability ● proteins exhibit chemical specificity → interacting only with one specific molecule ○ channels may be completely inhibited by similarly shaped molecules Active Transport ● membrane-bound protein transport Na+ /K+ pump using ATP as driving force ○ against (or, up) concentration gradient ● similar to facilitated diffusion: ○ can be saturated, exhibits chemical specificity, and shows competitive inhibition Osmosis ● water-diffusion typically toward equal volumes against solute CG (i.e. from [L] to [H]) ○ requires special pores (due to hydrophobic lipid layer) ● osmosis-causing particle → osmotically active particle ● number of osmotically active particles → osmole ● osmolality: number of osmoles per kilogram of water or per litre of solution ○ assume these two units of concentration are same ●

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Factors Affecting Osmosis a. solute-specific membrane permeability b. solute CG c. pressure gradient across cell membrane Isotonic, Hypotonic, and Hypertonic Solutions ● isotonic (=300 mOsm/kg): cell and solution equal in concentration (equilibrium) ● hypotonic (300 mOsm/kg): [solution] > [cell]; H2O฀ cell; cell shrinks Concentration Gradients and Membrane Permeabilities ● Na+, Ca2+  , and Cl- → [H] outside cell; K+ → [H] inside cell ○ membrane prevent diffusion of unwanted ions into or out of cell ○ Na+, Ca2+  , and Cl- lack ion channels in membrane; K+ can diffuse small amounts through membrane along gradient ● permeability changes under different circumstances ○ chemical changes, voltage, and stimuli Membrane Potentials ● charged particles move by electrical gradients (i.e. unlike attract, like repel like) ● electric potential (membrane potential): charge difference between inside cell- and outside cell+ a. equilibrium potentials b. resting membrane potentials c. action potential (AP) d. excitatory postsynaptic potentials and inhibitory postsynaptic potentials e. generator potentials Resting Membrane Potential (-70 mV) ● fluids inside and outside of cells electrolytic (ion-containing) ● excess (-) charge often accumulates directly inside cell; opposing (+) charge will accumulate outside cell ○ electrical potential difference results in “resting,” non-charged cells Equilibrium Potentials (E) a. chemical concentration gradient (CG)→ difference between [H] and [L] b. electrical gradient → difference between (+) and (-) ■ two forces equal in magnitude, but opposite charge = electrochemical equilibrium (no net movement) ● E value = charge that must be applied to prevent movement down CG i. E(K+) → -90 mV ■ K+ leakage occurs due to higher relative RMP ii. E(Na+) → +60 mV ■ Na+ attracted inner membrane due to opposite charge; membrane prevents free diffusion - iii. E(Cl ) → -70 mV ■ inner cell membrane electrically balanced to prevent Cl- from entering Sodium/Potassium (Na/K) Pump ● integral membrane protein pumps 3 Na+ out and 2 K+ in ● contributes to addition of negative charge to cell → electrogenic ● active transport against CG; works to maintain static CG Significance of Resting Membrane Potential ● excitable cells harness membrane potential for work in nerves and muscles Quick Look Back ● cell membrane selectively permeable barrier due to phospholipid bilayer (hydrophobic, hydrophilic) ○ proteins, channels, receptors, etc. transport ions, larger substances through membrane ● molecules transported by diffusion, facilitated transport, active transport, ion-gated channels, etc. ○ osmosis works to neutralize [H] solute ● Na+/K+ leakage→ resolved through Na+/K+ Pump; responsible for resting membrane potential (-70mV) ● tonicity: ability of solution to osmosis across cell membrane

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Module 4: Nerves Overview ● excitable → nerve, muscles cells utilize RMP to generate electrochemical impulse (AP) ○ nerve cell “communication” and muscle cell movement ● dendrites: thin, branching structures that receive electrochemical impulses ● cell body (soma): control center, containing nucleus, and organelles ● axon: projection of cell body, carrying outgoing AP impulses to other cells ● myelin sheath: lipid insulator limits ionic changes to nodes ● node of ranvier: small exposed axon regions where AP utilizes saltatory conduction along axon ● collaterals: axon branching; increase number of target cells for outgoing signals ● terminal bouton or axon terminal: swelling at end of axon collateral; containing mitochondria and membrane bound molecules; facilitate transmission of signal across synapse toward target cell Action Potential (AP) ● membrane potential rapidly reverses (-70mV to +35mV) ○ due to ionic movement across membrane (notably Na+ and K+ ) ● begins at axon hillock (largest number of voltage-gated channels) i. strong depolarization at axon hillock opens most Na+ channels ii. Na+ rushes through channels into neuron, down CG; depolarization to +35mV iii. Na+ channels inactivate while K+ channels activate iv. K+ rushes out of cell, down CG; repolarization back to -70mV v. ineffective channel closing, leaks more K+; hyperpolarizes cell to -90mV vi. MP slowly returns to - 70mV Voltage-Gated Channels (VGc) ● two types: a) Na+ and b) K+ ● VGc essential for propagating AP ● in neuron, VGc found in axon; as Na+ enters, depolarization occurs producing AP Voltage-Gated Sodium Channels (VG(Na+ )c) ● both inactivation and activation gates are on cellular side of membrane ● events at VG(Na+ )c occur as follows: a. membrane depolarization occurs with opening of activation gate; Na+ enters, flowing down CG b. after period: inactivation gate closes, Na+ can no longer flow into cell c. channel returns to resting configuration (inactivation gate open and activation gate closed) d. channel ready to operate again Refractory Periods ● absolute: period when, regardless of strength of depolarization, Na+ gates will not respond to AP ● relative: period during hyperpolarization when K+ ions slowly leak out; AP possible, but only with much stronger stimulus Voltage-gated Potassium Channels (VG(K+ )c) ● channels contain only single gate; activated by inactivation of Na+ channels a. membrane depolarization occurs; after brief pause, K+ voltage-gated channels open b. K+ flow out of cell, down ECG c. channel returns to resting configuration (activation gate closes) d. channel ready to operate again ○ unlike Na+ channel, no refractory period Threshold for Starting an AP ● APs do not always occur with depolarization ○ require strong depolarization at axon hillock to initiate opening of Na+ channels ● if smaller depolarization occurs, then cell works to maintain resting potential in order to fire AP, depolarizing force from Na + must exceed natural repolarizing forces from K+ and Cl_ ● threshold of -55mV

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Changes in Permeability/Conductance during AP Na+

K+

channels react quickly

channels react slowly

depolarizing stage due to Na+ entering cell higher (+) charge inside

repolarizing stage due to K+ leaving cell during Na+ impermeability shifts to (-) inside

Important Facts about APs ● very few ions transported during AP (1/17 of available ions) ● many thousand APs can be generated before ECG break down AP Propagation and Saltatory Conduction ● AP travels (or propagates) down from axon hillock to axon terminal ● if threshold not reached, natural repolarizing force return cell to RMP ○ therefore, all-or-nothing principle applies: either AP is propagated fully or not at all a. unmyelinated nerve: AP propagation 1. following depolarization: (+) charge exists inside membrane (+35mV) 2. (+) charge attracted to (-) resting areas→ area depolarize ■ absolute refraction guarantees unidirectional propagation 3. depolarization triggers VG(Na+ )c to open ■ Na+ rushes into cell, depolarizes region beyond threshold 4. through this process, AP propagates along membrane b. myelinated nerve: saltatory conduction ○ myelin (fatty insulating material) produced from Schwann cells or oligodendrocytes ○ saltatory conduction faster than unmyelinated conduction ○ insulates axon to prevent ionic leakage; ■ dissipates signal→ VGc only present at gaps nodes of Ranvier 1. node of Ranvier - at RMP attracts existing AP+ toward it 2. node of Ranvier depolarizes, opening Na+ channels 3. Na+ enters, depolarizes region beyond threshold potential → new AP+ generated 4. through this process, myelinated nerves propagate APs Multiple Sclerosis ● autoimmune disease causes severe damage to myelin sheaths; result in diminished AP propagation leading to limited mobility or paralysis Synaptic Transmission ● chemical synapse: connection between neuron and nerve, muscle, or other organ cell ● neuromuscular junction (NMJ): connection between neuron and muscle cell where APs exchange Structure of Neuromuscular Junction ● motor nerve fiber → neuron that contacts muscle cell ● (presynaptic) axon terminal contains Ca++ voltage-gated channels ○ also triggered by membrane depolarization ● neurotransmitter acetylcholine (ACh) synaptic vesicles found in axon terminal ● sarcolemma end plate contains acetylcholinesterase  (AchE) transport pathway? ● acetylcholine receptors also present, associated with ligand-gated  ion channels Events at NMJ a. presynaptic motor nerve fiber AP triggers Ca++  voltage-gated channels to open ○ Ca++ flows into synaptic cleft, down CG b. Ca++ triggers fusing of synaptic vesicles to presynaptic membrane ○ ACh exocytosed to synaptic cleft

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c. d. e. f.

ACh diffuses across synaptic cleft; attaches to channels/receptors on muscle cell/fiber membrane ACh binds, triggers ligand-gated Na + ion channels in end plate potential (EPP) depolarization EPP depolarization and Na+ inflow initiates AP propagation across muscle fiber ACh digested into acetic acid and choline by AChE enzyme; choline reused in axon terminal

Module 5: Muscles Introduction ● muscles utilize chemical energy (ATP) from metabolism to perform useful work ● 3 types of muscles: a. skeletal: voluntary motion b. smooth: walls of blood vessels, airways, various ducts, urinary bladder, uterus, and digestive tract c. cardiac: heart ● 3 principal functions: a. movement b. heat production c. body support and posture Whole Look at Structure of Muscles ● whole muscles → bundles of fasciculi surrounded by perimysium (white connective tissue) ● fascicle → groups of long, striated muscle cells or fibres ● muscle cell → bundles of myofibrils ● myofibrils → thin and thick myofilaments ● thin myofilaments → proteins actin and trace amounts of troponin and tropomyosin ● thick myofilaments → protein myosin ○ thin and thick myofilaments interaction results in muscle contraction Structure of Skeletal Muscle ● muscle cells (or fibres) → long, striated fibres with multiple nuclei surrounded by sarcolemma (muscles cell membrane) ● small tube-like projections transverse (T) tubules extend down cell ○ T tubules conduct AP deep into cell to contractile proteins ● long, cylindrical myofibrils contain c ontractile proteins (thin and t hick microfilaments)  ) → essential for ● sarcoplasmic reticulum (SR) surrounds myofibrils; contains mesh-like tube network of calcium ions (Ca++ contraction ● at either end of SR are terminal cisternae (membranous enlargement of SR) Thin Myofilament ● composed mostly of globular protein actin (purple balls) ○ each actin contains site for myosin (concavities in purple balls) ○ long tropomyosin (turquoise strand) proteins cover binding sites for myosin at rest

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 troponin A: binds to actin, troponin T: binds to tropomyosin, troponin C: binds with Ca++ at rest, troponin A, T complex holds tropomyosin to cover myosin binding sites when Ca++  binds to troponin C, tropomyosin removed from myosin binding sites by troponin Thick Myofilament ● composed of many myosin molecules arranged to form one thick filament→ long, bendable tail with two heads/bindings sites on each side ● another site binds ATP → releases energy powering contraction Actin/Myosin Relationship ● thin (actin), thick (myosin) myofilaments in repeating pattern along myofibril ● region between z disk to another → sarcomere (smallest contractile unit) ○ each thin group extends laterally from central Z disk (line) ○ each thick group extend laterally from central M line ○ each myofilament is parallel to length of myofibril and muscle cell ● repeating pattern gives striated or banded appearance ○ thick filaments appear as dark A bands ○ thin filaments appear as lighter I bands ● ● ●

Muscle Contraction - Sliding Filament Theory ● interaction between actin and myosin leads to muscle contraction ● sarcomeres shorten/compress: a. head of myosin molecule attaches to binding site on actin → forms crossbridge b. change in shape causes myosin head to swing, propelling forward → produces power stroke c. power stroke slides actin past myosin; ● throughout process neither thin nor thick filaments shorten during muscle contraction but rather slide along to fill in space Excitation-Contraction Coupling and Muscle Contraction ● excitation-contraction coupling → AP in sarcolemma excites muscle cell to produce muscle contraction a. AP produced at NMJ spreads over sarcolemma, down T-tubules into muscle cell core b. AP travels near SR, opening Ca++  channels, causing release of Ca++  from terminal cisternae Ca++ binds to troponin C on thin myofilaments, causing tropomyosin to uncover myosin binding sites on actin d. myosin can now attach and initiate power stroke Relaxation of Muscle c.

● once AP ends, Ca++  no longer diffuses out of SR  back into SR, against CG(ATP consuming) ● Ca++ pumps rapidly expel Ca++ ● without Ca++  present, tropomyosin recover myosin binding sites again ● actin will be unable to bin...