BLOCK 1 PHYSIO-I REVIEW

Homeostasis= maintenance of bodys internal environment by regulating set points.

Total body water= 60% wt ~42L
Intracellular Fluid 28L (2/3 body water)= within cell cytoplasm
Extracellular Fluid 14L (1/3 body water, interstitial fluid, & plasma)= blood w/o cells & ultra-filtrate plasma

Milliequivalent quantities (mEq/L=mM*valence)
Steady State Balance not equilibrium bc vary in solute concentrations that must stay within specific range.
Homeostatic conditions of the internal environment has constant osmolality of ECF & ICF ~300mOsm/Kg
ECF Osmolality= 2*plasma [Na+]~300mOsm/kg H2O (determinant Osmolality of persons blood)
ICF Osmolality=2*cellular [K+]~300mOsm/kg H2O
>300mOsm hyperosmotic, <300mOsm hypoosmotic, ~300mOsm isosmotic
Homeostatic Control: Sensor (chemoreceptors, baroreceptors) determines change from Set point,
established via Control center, this change in Parameter (essential narrow range) will initiate the control
center to stimulate an Effector with a response that typically corrects change via feedback.
Ex: Low BV, BP,& hyperosmolality are sensed via baro- & chemo-
receptors, this signals thirst, increased water retention (ADH) in kidneys,
increase HR to act as effectors to regain fluid balance and raise BP.
Ex: Fed state rising glucose levels (>70-90mg/dL) stimulate pancreas B
cells to release insulin & hepatocytes to recruit GLUT-2 transporters to
PM. Insulin recruits GLUT-4 transporters that induce glucose uptake into
cells (liver, muscle, heart) for storage as glycogen or glycolysis. As cells
take up glucose, blood glucose levels decrease and return to homeostasis.
+ Feedback mechanism amplify signal or product auto-stimulates further release until major event occurs.
Ex: Parturition (labor) is a +FB mech in which the head of fetus pushes against cervix, baroreceptors sense
stretch and stimulate post pituitary neural release of Oxytocin, which is carried to uterus to stimulate uterine
contractions. Further contractions stimulate further stretching and this continuous cycle of Oxy release
amplifies until birth of the baby.
Ex: Production of an Action Potential occurs when a stimulus causes an EPSP to slightly depolarize the
membrane potential. This stimulates opening of Voltage-gated Na+ channels (VGNCs), influx of Na+ into
the cell further depolarizes the membrane potential in an amplificatory manner until threshold is reached
and an AP is initiated and propagated.
The Plasma Membrane is a phospholipid bilayer containing many PLs (amphipathic lipids) with
hydrophobic tails in intermembrane space and hydrophilic heads outside and inside the cell membrane. PLs
are primarily composed of 2FAs + Glycerol + Phosphate + functional group (Ethanolamine, serine, inositol,
choline, etc) and some Sphingomyelin PLs.
Fluid Mosaic Model of the PM has the PL bilayer w/ many membrane proteins (integral or peripheral),
carbohydrates (may be lipid/protein bound), and cholesterol. Unsaturated PLs create kinks (C=C) and
increase fluidity of the PM. Cholesterol stabilizes unsat-PLs. Saturated PLs (C-C) reside in rigid lipid rafts.
NERNST
EQUATION gives
Ion Equilibrium
Potentials

BLOCK 1 PHYSIO-I REVIEW
Vesicular Transport via endocytosis, exocytosis, organelle vesicular fusion allows transport of
nonpermeable particles within the cell. (Phagocytosis, pinocytosis, clathrin coated vesicles, exocytosis)
Passive Diffusion: transport of particles through PM down concentration gradients (chemical driving force)
o Permeability coeff, solubility, molecular size, and charge all affect simple diffusion.
o Electrical potential difference in PM will attract/repel ions toward opposite/like charge w/o conc grad.
Ficks Law of Diffusion: J=DAC/X Net flux Solute=(Diffusion coeff)(CSarea)(Conc differ)/Distance
o High D, A, C cause high net flux; high X cause low netflux
Van Hoffs Equation: =gCRT determines Osmolarity of solution via dissociation of solutes in solution
Osmotic pressure=(#compounds dissociated)(Conc)(Ideal gas constant)(absolute Temp)
RT typically constant thus omitted. 150mM NaCl*2 ions= 300 mOsm/L osmolarity=osmotic pressure
Osmotic coefficients () illustrate deviation of solutes from ideal behavior
NaCl =0.93*300mOsm/L=279mOsm/L NaCl true osmotic pressure
Permeant/permeable solutes such as Urea can cause transient changes in osmolarity as they flow down
concentration gradients in attempt to reach equilibrium (loss of change).
Tonicity is determined by Impermeant solutes (NaCl). This determines steady state balance of the cell.
140mM NaCl= 280mOsm/L isotonic solution no change in cell volume
180mM NaCl= 360mOsm/L hypertonic solution pulls water out cell shrinking cell volume (creanate)
100mM NaCl= 200mOsm/L hypotonic solution pushes water into cell swelling volume (lysis)
Cell Volume Regulation: 375mOsm/L>changes<275mOsm/L, greater difference causes cell death
Hypotonicity Regulated Volume Decrease (RVD) increases K+/Cl- cotransporter efflux
Hypertonicity Regulated Volume Increase (RVI) increases Na+/K+/Cl- cotransporter influx
Protein Mediated Transport: carrier reaction rates, saturation, specificity, and competitive inhibition
Channels facilitate downhill transport, active site is simultaneously accessible from both sides
o Aquaporins transport water molecules (RBCs, alveoli, nephron, GIT lumen)
o Nonselective pores (Gap Junctions) allow passage of soluble molecules and electrical currents
o Ion channels: Leaky-always open, maintain resting membrane potential; Gated-only open period (closed
at rest) and primarily determined by membrane potential, ligands, chemicals, mechanical stimulants.
Na+ gated, Ach sensitive (nicotinic rec) gated for Na+, pressure Na+ (pacinian corpuscle)
Carriers facilitate downhill transport, active site only accessible from one side at a time
o Specific proteins are essential for transport of substances, GLUT transporters, AA transporters
Pumps facilitate transport AGAINST conc gradients and require some form of energy (Active Transport).
o Primary Active Transport: ATP breakdown for energy
Na+/K+ ATPase pump is most abundant dimer pumps, uphill transport uses conformational
change to expel 3 Na+ out of cell (ATP) and 2 K+ into cell. Found on basement membranes.
Cardiac Glycosides (Digoxin) block Na+/K+ ATPase to increase ICF [Na+] which
increases EC coupling, produces lower threshold for contractility, and increases CO.
Ca2+ ATPase pumps out of cell, H+/K+ ATPase H+ for HCl of parietal cells in stomach
o Secondary Active Transport: ionic concentration differences create electrical gradients as energy
Symporters co-transport in same direction: Na+/Glucose, Na+/AA, NaCl, KCl
Typically found apical/luminal side of cells
Furosemide (Lasix) & Thiazide blocks Na/Cl cotransporters (diuretics)
Antiporters counter-transport in opposite direction: 3Na+/Ca2+, Na+/H+, Cl-/HCO3-
Difference from Carrier mediated transport: uphill transport & requires energy
BLOCK 1 PHYSIO-I REVIEW
Transport Pathways: Paracellular pathway through leak tight junctions (TJs) in lateral intercellular space.
Lumen of the intestines and nephrons begin very leaky (Duodenum & PCT) then become tight (Ileum &
DCT/CD) for efficient solute reabsorption. Transcellular pathway through cell (endo- & exocytosis), into
cells from apical or basolateral membranes.
o ENaC= Epithelial Na Channel on apical surface of cells, if it is blocked in nephritic cell walls,
resorption of Na is reduced, tubule increase [Na] stimulates osmosis out of cell to form urine (diuresis).
Ionic Distributions determine chemical and electrical driving forces of concentration gradients. The sum of
these forces gives the electrochemical driving force with a net flow of direction.
Nernst Equation E=60/z*log[Eo]/[Ei] calculates Equilibrium Potential necessary to match the force of a
chemical gradient of specific ions.
o If the chemical and electrical forces are in opposite directions:
E(ion) > membrane potential then chemical force>electrical force & net flux follows chemical
E(ion)< membrane potential then electrical force>chemical force & net flux follows electrical
o E potential difference of about 60mV is required to balance 10x conc difference of univalent ion
[K+]i=140mM[K+]o=14mM movement of cation out cell E= -60mV
[Na+]i=15mM[Na+]o=150mM movement of cation into cell E=+60mV
100x difference requires 120mV; 1000X difference requires 180mV etc
o E potential difference of about 89mV is required to balance 30x conc difference of univalent ion
[Cl-]i=3.33mM[Cl-]o=100mM move of anion into cell E= -89mV
Resting Membrane Potential (Vm) is maintained by leaky Na+ & K+ channels down electrochemical
gradients. Na+/K+ ATPase contributes ~4mV to RPM.
Goldman-Hodgkin-Katz Equation is used to calculate RPM
Vm=61*log PK[K+]o + PNa[Na+]o + PCl[Cl-]i
PK[K+]i + PNa[Na+]i + PCl[Cl-]o
RMP approaches the E potential for any ion whose permeability increases compared to others.
If PK increases then RPM approaches -95mV (a 10x fold change in [K+]o will change RPM by 60mV)
If PNa increases then RPM approaches +61mV
If PCl increases then RPM approaches -85mV (not as many Na/Cl channels for conc change to affect RPM).
Conductance (g=1/R) describes ability of an ion to carry electrical current across the PM. Ohms Law
predicts amplitude of Ion Flux current (pA) I=(Vm-Eion)/R (Resistance typically=1)
o +pA ion flux moves out cell; pA ion flux moves into cell
Membrane potential can be measured via electrophysiology w/ pipette electrodes.
Depolarization is a decrease in potential difference (more positive RMP, increased excitability)
Hyper or repolarization is an increase in potential difference (more negative RMP, decreased excitability)

BLOCK 1 PHYSIO-I REVIEW
An AP is a depolarization of the Vm for a brief time.
It is created by switching permeability of K+ at rest
to Na+ for excitability.
Na+ channels have 2 gates (1 active and 1 inactive),
K+ channels have single activation gate.
Resting Level: high K+ permeability out cell Vm~ -60mV
Both activation gates of K/Na are closed, Na+
inactivation gate is open.
Threshold: EPSP (cations move into cell) slightly
depolarizes Vm~ -55mV which actively recruits voltage-gated Na+ channels to open and further depolarize.
Rising Phase: + Feedback further depolarizes Vm and critical number voltage-gated Na+ channels open.
Na+ activation gates continually open for Na+ influx. K+ activation gate is still closed.
Overshoot: Vm reverses polarity and membrane is most permeable to Na+ influx (approaches ENa)
Peak: At or near top Na+ permeability begins to decrease as first recruited voltage-gated channels close and
K+ permeability increases efflux as voltage-gated K+ channels open.
All Na activation gates are open, first recruited Na inactivation gates begin to close. Some K+ activation
gates begin to open for K+ efflux.
Repolarization: Change in conductance drives Vm EK as K+ efflux increases and Na+ influx decreases.
All K+ activation gates are open and Na+ inactivation gates continually close.
Afterhyperpolarization: Vm is more negative due to continued K+ efflux, when voltage-gated K+ channels
close the Vm will go back to resting Vm ~60mV.
Na+ inactivation gates are closed and K+ activation gates begin to close.
Measure of APs can be done using electrophysiology pipettes or isolate channels within electrode patches
both visualize change in voltage within ion channels. (downward deflection amplitude is an inward
current depolarization of Vm)
Ionic Conductances that generate Aps can be blocked by channel inhibitors:
o Tetrodotoxin (TTX) and Saxitoxin (STX) are Na+ channel inhibitors that block depolarization
and there prevent APs even in presence of EPSP, lowered Vm.
o Tetraethylammonium (TEA) is a K+ channel inhibitor that blocks repolarization and sustains AP,
however eventual inactivation of voltage-gated Na+ channels will overtime lead Vm back to rest.
APs can propagate without decrement in an all or none response w/ voltage inactivation.
Refractory Periods for APs determine ability to produce a new AP.
o Absolute RP= During the AP peak where cell CANNOT start new AP.
o Relative RP= During afterhyperpolarization in which a new but smaller AP CAN begin.
The threshold for APs during the relative RP increase thus require larger stimulus.
Accommodation is when a nerve is depolarized slowly and normal threshold may be passed w/o AP
firing. High [K+] (hyperpolarization) due to Hyperkalemia prevents depolarization by inactivation of
voltage-gated Na+ channels, so no AP. The increased gK makes it less likely to excite.
BLOCK 1 PHYSIO-I REVIEW
Propagation of an AP through axons; AP initiated at axon hillock & sent to a postsynaptic cell
Rate of Propagation is affected by passive properties of axonal membranes:
Space (length) constant = Sqrt(Rm*d)/4Ri= Sqrt(resistance*diameter axon)/(4longitudinal resistance)
The greater the length, the greater the propagation velocity
Time constant = RmCm = (Resistive properties =1/permeability)* (Capacitance=ability to store charge)
Smaller = greater ability of membrane to respond rapidly to stimulus and greater propagation velocity
Types of nerve conduction: unmyelinated axons electronic conduction velocity is proportional to diameter
& myelinated axons saltatory conduction velocity is proportional to distance between nodes of Ranvier.
Saltatory conduction in myelinated axons nodes of Ranvier propagation occurs through new APs.
o Schwan cells secrete myelin layers in PNS, Oligodendrocyte cells wrap axon and secrete myelin in CNS
Synapses transmit information between neurons by influencing excitability of postsynaptic neuron (delay,
diverge, converge, repeat, or sustain transmission) soma=cell body
Electrical Synapses (via Gap junctions w/ bidirectional flow of ions/small molecules to adjacent cells)
Chemical Synapses (most predominant via unidirectional vesicle exocytosis and postsynaptic receptors)
1. NTs are packed into synaptic vesicles and propagated along axon
2. AP arrives at the presynaptic terminal and stimulates voltage-gated Ca2+ channels to open
3. Ca2+ influx depolarize and triggers fusion of synaptic vesicles with presynaptic membrane
4. Vesicle docks via neural SNARES (synaptobrevin to syntaxin), Synaptogamin senses Ca2+ influx
binds and catalyzes membrane fusion. (exocytosis)
5. NTs diffuse across PM into postsynaptic cell synaptic cleft to bind postsynaptic membrane receptors
6. Activation of channels by synaptic current produces a postsynaptic potential (delay w/ diffusion)
7. Postsynaptic potential depolarization stimulates another AP to propagate the signal.
Synaptic Contacts: Axodendritic (proximity of synapses to trigger zone determines effectiveness),
Axosomatic (stronger signal and greater influence on outcome at trigger zone), Axoaxonic (regulated
release of NTs regulate effectiveness, no effect on trigger zone)
NTs at synapse will bind receptors, diffuse away, reuptake by postsynaptic cell, or breakdown (metabolite)
Quanta= release of NTs in small packets (# vesicles), Quantum= amount of NTs in a vesicle,
Unit synaptic potential= postsynaptic potential change proportional to quantum
Drugs Affecting Neural Transmission: TTX & STX block Na+ channels; Dendrotoxin (DTX) blocks
K+ channels; Tetanus & Botulism block synaptobrevins (ACh release); d-Tubocurarine & a-
Bungarotoxin block ACh receptors (nicotinic)
EPSP= excitatory postsynaptic potential from a stimulus to initiate threshold and depolarization to AP
IPSP= inhibitory PSP from a stimulus to initiate hyperpolarization to prevent threshold and AP
Temporal Summation: Consecutive synaptic potentials arrive at postsynaptic cell and add together
Spatial Summation: Two separate inputs from different directions arrive simultaneously at postsynapse

BLOCK 1 PHYSIO-I REVIEW
Ionotropic Receptors: Direct ion gated postsynaptic receptors (neuroactive substance FAST response)
o ex: ACh stimulate Na+ channel directly to depolarize for muscle contraction.
Metabotropic Receptors: GPCR that links ion channel indirectly (NTs w/ DELAY signal, 2
nd
messengers)
o Ex: ACh stimulates GPCR (muscarinic), B-G subunit activates K+ channel to hyperpolarize
for decrease heart rate.
Neurotransmitters: synthesized in soma, present in presynaptic terminal, released in Quanta to stimulate a
unit synaptic potential, exogenous or endogenous NTs have same action, specific down regulation mech.
o Small molecule NTs: rapid acute responses of CNS/PNS (sensory and motor signals)
o Neuropeptides: prolonged chronic responses, typically neuromodulators (# receptors, period
open/close ion channels) released a distance from postsynapse, actions terminated by proteases.
NT Nerve RECEPTOR Regulation FUNCTION
Acetylcholine
(ACh)
ALL
preganglionic,
Postganglionic-
PNS
Cholinergic: nicotinic (iono),
muscarinic (meta),
ACh-esterase enz
Curare (rabies)
inhibits nAChR,
atropine inhibits
mAChR
Movement, cognition,
ANS rest & digest
Dopamine (Da) Midbrain
neurons
Dopaminergic (D1 & D2) Imipramine, cocaine
inhibit
Movement, affect,
reward
Glutamate (Glu) CNS AMPA, NMDA (reqs Gly),
Kainate, Quisqualate A
(iono), QB (meta)
PCP inbits NMDA Excitation (EPSPs),
learning, memory
Glycine (G) Lower CNS Ligand gated Cl- channels Inhibition
GABA Stabilize
electrical
activity in brain
GABAa (iono)=Ligand
gated Cl- channels
GABAb (meta)=GPCR to
activate K+ channels block
Ca2+
Benzos enhance
GABA (valium).
Picrotoxin/bicuculline
inhibit
Inhibition (IPSPs),
learning & memory
Nitric Oxide (NO) Vasodilation, metabolic
Norepinephrine/
epinephrine
(NE/E)
Postganglionic-
SNS, adrenal
medulla
Adrenergic (a & B) Imipramine, cocaine,
pargyline
Fight or Flight, alertness
Serotonin (5-HT) brain Inhibitory effects on 5-HT
receptors
Selective Serotonin
reuptake inhibitors
(SSRIs)-prozac, paxil,
Zoloft, lexapro
Mood, arousal, pain,
appetite by increasing
[5-HT] in blood
(dysfunction=depression
& bipolar, etc)
Catecholamine Synthesis (NE/E): TyrL-DopaDaNEE
Synaptic Integration: Input-Output relations:
Single Synapse (1:1 APs in pre and post synaptic cells)- NMJ
Divergence (1:many APs amplify a signal in postsynaptic cells)- Renshaw cells of CNS
Convergence (many:1 APs at target cell integrates signals from many sources)- Motor neurons PNS
Local graded potentials (EPSPs, IPSPs, receptor potentials) code information via amplitude
Weak stimuli evoke small potential intensities, and strong stimuli evoke large potential intensities.
Stronger stimuli activates greater # of receptors, thus intensity corresponds to receptor population size.
Increase amplitude & duration of receptor potential will increase frequency & duration of APs (w/
exponential decrease as NTs run out)
Regulation of information Transfer:
Presynaptic Inhibition=IPSPs at presynaptic terminal decreases postsynaptic potential (GABA, tetanus..)
Presynaptic Facilitation=EPSPs at presynaptic terminal increase postsynaptic potential (Glutamate)
Synaptic Plasticity: facilitation (increase strength), potentiation (increase #NTs), or depression (fatigue)