Physiology Block 1 Review SPRING 2025 PDF

Physiology Block 1 Review SPRING 2025  HOMEOSTASIS IS A STEADY STATE Homeostasis occurs at a price: energy Equilibrium: a state that does not involve energy consumption →when a vital parameter (e.g., the blood glucose level) is well regulated, that parameter is not in equilibrium Stead...

Physiology Block 1 Review SPRING 2025  HOMEOSTASIS IS A STEADY STATE Homeostasis occurs at a price: energy Equilibrium: a state that does not involve energy consumption →when a vital parameter (e.g., the blood glucose level) is well regulated, that parameter is not in equilibrium Steady state: →When a vital parameter is well-regulated →value is constant because the body or the cell carefully matches actions that lower the parameter value with other actions that raise it →the net effect is that the vital parameter is held at a constant value 2  NEGATIVE FEEDBACK: MOST COMMON FEEDBACK MECHANISM Self-limiting Reverses any deviation of the controlled variable from its stable point In general, if some factor becomes excessive or deficient, a control system initiates negative feedback, which consists of a series of changes that return the factor toward a certain mean value, thus maintaining homeostasis Review all the examples of negative feedback given. Returns variable to original set point 3  POSITIVE FEEDBACK: UNCOMMON FEEDBACK Positive feedback loop: maintains the direction of the stimulus, possibly accelerates i Self- augmenting Tends to exaggerate deviations of the controlled variable from its stable point Each cycle of this feedback leads to more of the same variable May cause a vicious cycles which can lead to more instability and death Less common than negative feedback Recall all the examples of positive feedback given. 4  Electrolyte content of Body Fluids Review the electrolyte content of the body fluids.  EFFECTIVE OSMOTIC PRESSURE: Reflection Coefficient (σ) Review the relation of osmotic pressure and reflection coefficient.  An isotonic solution is always iso-osmotic, BUT an iso-osmotic solution may not be isotonic when substances have reflection coefficient of 0 (σ = 0).  Urea is freely permeable and can move across the membrane → rapidly equilibrates between the 2 compartments: “Ineffective osmole”  It is the concentration of the impermeable solute(s) that determines osmotic pressure and consequently the movement of water. 6  TONICITY OF SOLUTIONS What are the effects of placing a cell in solutions of different tonicities? The terms isotonic, hypotonic, and hypertonic refer to whether solutions will cause a change in cell volume The tonicity of solutions depends on the concentration of impermeant solutes (σ = 1.0) Some solutes can still permeate the cell membrane 7 Review the effects of volume changes on osmolarity of body fluids. 8  TRANSPORT FUNCTION OF THE PLASMA MEMBRANE TRANSPORT PASSIVE OR ACTIVE TRANSPORT DISTINCTIVES EXAMPLES SIMPLE Follows the  Through the phospholipid layer O2, CO2, DIFFUSION electrochemical glycerol, gradient  Through protein channels or Na+, K+, H2O pores FACILITATED Follows the  Requires a protein carrier Fructose DIFFUSION electrochemical (GLUT5) gradient PRIMARY ACTIVE Against the  Uses ATP directly Na+-K+ ATPase electrochemical  Through a protein carrier Ca++ pump gradient (SERCA) SECONDARY Against the  Uses the electrochemical Na+-glucose ACTIVE electrochemical gradient produced by the (SGLT1) gradient primary active transport (Na+ Na+-Ca++ gradient) exchanger  Through a protein carrier Na+-amino acid BULK TRANSPORT Against the  Endocytosis – bulk intake of WBC electrochemical substances gradient  Exocytosis – bulk secretion of Neurotransmitt substances ers (Ach), 9  FICK’S LAW OF DIFFUSION - relates the diffusive flux to the gradient of the concentration What factors affect the rate of diffusion across the cell membrane? KDAC P = KD/∆X  J = PA J X Where: ∆C J = the amount of substance that will flow through a unit area during a unit time interval P = permeability coefficient K = partition coefficient (solubility in oil) D = diffusion coefficient (size of solute particle and viscosity of solution) ∆X = thickness of the membrane A = cross sectional area involved in diffusion ∆C = the difference in concentration of the substance between the two compartments *Temperature - the higher the temperature, the higher the rate of diffusion 10  1. SATURATION IN CARRIER-MEDIATED TRANSPORT Review the characteristics of carrier transport. o Based on the concept that carrier proteins have a limited number of binding sites for the solute o At low solute concentrations, many binding sites are available and the rate of transport increases steeply as the concentration increases o At high solute concentrations, the available binding sites become scarce and the rate of transport levels off o Transport maximum, or Tm – point in time when all of the binding sites are occupied Clinical significance: Tm-limited glucose transport in the proximal tubule of the kidney results in spillage of glucose in the urine when 11  2. STEROSPECIFICITY IN CARRIER-MEDIATED TRANSPORT Review the characteristics of carrier transport. o Binding sites for solute on the transport proteins are stereospecific/stereoselective o Clinical significance: the transporter for glucose in the renal proximal tubule recognizes and transports the natural isomer D-glucose, but it does not recognize or transport the unnatural isomer L-glucose 12  3. COMPETITION IN CARRIER-MEDIATED TRANSPORT Review the characteristics of carrier transport. o Although the binding sites for transported solutes are quite specific, they may recognize, bind, and even transport chemically related solutes o The transporter for glucose is specific for D-glucose, but it also recognizes and transports a closely related sugar, D-galactose o D-galactose inhibits the transport of D-glucose by occupying some of the binding sites and making them unavailable for glucose 13  ION CHANNEL CHARACTERISTICS What is conductance? What are the different types of protein channels?  Conductance(g) of a channel depends on the probability that it is open o The higher the probability that the channel is open, the higher is its conductance or permeability o speeds up the rate of diffusion  Gates on ion channels are controlled by different types of sensors 1) Voltage-gated channels: respond to changes in membrane potential 2) Ligand-gated channels: responds to changes in ligands such as hormones or neurotransmitters 3) Second-messenger-gated channels: respond to changes in signaling molecules 4) Mechanically-gated channels: respond to changes in membrane tension 14  MECHANISMS RESPONSIBLE FOR THE RESTING MEMBRANE POTENTIAL What factors determine the difference in concentration of substances across the cell membrane? Chemical gradients generated by active transport pumps (mainly Na+-K+ ATPase pump): the concentration of ions are significantly different between the intracellular and extracellular fluid, e.g. the ratio of potassium ions is 35:1 Selective membrane permeability: the cell membrane is selectively ion- permeable, specifically it is much more permeable to potassium (K+) ions Electrical gradients are generated because potassium leak (via K2P channels) from the intracellular fluid creates a negative intracellular charge intracellularly: this charge attracts potassium ions back into the cell and thus opposes the chemical gradient Electrochemical equilibrium: develops when electrical and chemical forces are in balance for each specific ion species - described by the Nernst equation 15  EQUILIBRIUM POTENTIAL What is equilibrium potential and what is its relation to membrane potential? The equilibrium potential for an ion is the membrane potential at which the diffusive force (chemical gradient) is exactly balanced by the electrical force (electrical charge) The ion always diffuses in a direction that brings the Em (membrane potential) toward its equilibrium The overall current flow of the ion is directly proportional to the net force and conductance (determined by ion channel state, i.e., permeability) of the membrane for the ion The Em moves toward the equilibrium potential of the most permeable ion The number of ions that actually move across the membrane is negligible. Thus, opening of ion channels does not alter intracellular or extracellular concentrations of ions under normal circumstances 16  DRIVING FORCE FOR DIFFUSION: EQUILIBRIUM POTENTIAL VS. RMP When RMP is -70 mV, driving potentials for How does driving force affect the diffusion of ions across th diffusion of ions are: for K+ = -70 - (-94) = 24 cell membrane? E =120 Ca mV for Cl- = -70 - (-90) = 20 100 +120 mV mV for Na+ = -70 - 60 = -130 80 Membrane potential (mV) mV for Ca2+ = -70 - 120 = - 60 ENa = +60 190 mV mV 40 At equilibrium chemical IF driving force is: force = electrical force → 20 Negative net force = 0 (+) ion or cation will enter 0 the cell (-) ion or anion will leave -20 the cell Net driving potential for Positive -40 diffusion = RMP - (+) ion or cation will leave Equilibrium potential the cell -60 (-) ion or anion will enter RMP: -70 -80 the cell mV ECl = -90 -100 mV EK = -94 mV 17  CHARACTERISTICS OF ACTION POTENTIALS What are the characteristics of action  Stereotypical size and shape potentials? o Each normal AP for a given cell type: looks identical depolarizes to the same potential, and repolarizes back to the same resting potential  Propagation o the action potential is generally propagated down the entire length of the axon without decrement (non- decremental) Action potential of neurons, skeletal o it maintains its size and shape because muscle and cardiac muscle it is regenerated as it travels along the axon  All-or-none response o only a threshold or suprathreshold stimulus produces an AP o any stimulus below threshold will not 18 What are the sequence of events that occur during an action potential?  REFRACTORY PERIODS Differentiate between absolute and relative Absolute Refractory Period refractory periods. During this period, no matter how great the stimulus, no new AP can be elicited Basis: Inactivation gates of the Na+ channels are closed during depolarization These inactivation gates are in the closed position until the cell is repolarized back to RMP or slightly earlier Relative Refractory Period RRP begins at end of ARP and overlaps primarily with the period of the hyperpolarizing afterpotential AP can be elicited, but only if a greater than usual depolarizing (inward) current is applied Basis: Higher K+ conductance than is present at rest Because membrane potential is closer to K+ equilibrium potential, more inward current is  PROPAGATION OF ACTION POTENTIALS How are action potentials propagated along a nerve axon? Propagation of APs down a nerve or muscle fiber occurs by spread of local currents from active regions to adjacent inactive regions Action potential propagation in a neuron At rest, the entire nerve axon is at RMP, with the cell interior negative APs are initiated in the initial segment of the axon (hillock), nearest the nerve cell body then they are propagated down the axon by spread of local currents FACTORS AFFECTING CONDUCTION VELOCITY IN NERVES Review the factors affecting conduction velocity. What are Membrane resistance, Internal Resistance and Capacitance?  Review the different receptors, signaling pathways and messengers Receptor Class 1stinvolved. messenger Signal transduction pathway 2nd messenger Ligand-gated ion GABA, Ach (muscle), Opening/closing of channels – None channels ATP, glutamate, NMDA membrane currents: Na+, K+, Ca++, Cl- G protein-coupled Ach, peptides, cytokines G proteins: α and βꝩ Gs: cAMP (GPCRs) receptors odorants, lipids Gq: DAG, IP3 – Ca++ Gi: inhibits AC, K+ G12: RhoA Enzyme-linked Insulin, EGF, Receptor tyrosine kinase multiple receptors erythropoietin Adhesion molecules, Receptor tyrosine phosphatase suppress their neurotrophin receptors enzymatic activity upon ligand binding ANP Receptor Guanylate cyclase cGMP TGF-β Receptor Serine/Threonine multiple kinase Nuclear receptors Steroid hormones: Bind to regulatory sequences in estrogen, DNA and increase or decrease testosterone gene transcription