Physiology Lecture 1 & 2 Notes

Water Distribution
 Human body is – 50-75% H2O by weight
 Variation of H2O is inversely related to adipose tissue
o More fat, less water

Body Fluid Compartments

 Extracellular (30% H2O)
o Plasma (25%)
o Interstitial Fluid (75%)
 Transcellular (1%): CSF, joints, pleura
 Intracellular (67%)

Body Fluid Constituents

Ions Important for ECF ICF Resting Equilibrium
Resting Action Permeability Potential
Potentials and
Synaptic Potentials
Na+ 145 mEq/L 12 mEq/L Low +66
K+ 4 mEq/L 155 mEq/L High -97
Ca++ 5 mEq/L < 1 mEq/L
Cl- 120 mEq/L 4 mEq/L Very High -90
A- (organic anion) 0 HIGH Zero

Osmolarities
 Aquaporin channels- water moves freely
 Cell membranes are almost completely impermeable to most solutes
 Number of osmoles = amount of solute; generally remains unchanged in ICF and ECF
 ECF solute concentration is altered by: IVs, dehydration, water intoxication
 Osmolarity- determined by the number of solutes in a solution
 1 mole of a substance is its molecular weight in grams
 Normal ECF and ICF osmolarity is 300 mOsm
 Osmosis- movement of H2O across membrane due to solute’s concentration gradient
 Osmotic pressure- pressure that is applied to stop fluid movement
 Tonicity- cell expands/swells or contracts/shrinks when put into a solution
o Isotonic: cell does not swell nor shrink
 Isotonic Expansion- 1L 0.9% Na enters the body, fluid increases but
osmolarity stays the same so no fluid shift
 Isotonic Contraction- lose 1L of blood, no osmolarity change, no water
movements, just decreased ECF
o Hypotonic: cell swells; osmolarity inside cell is greater than outside cell so water
moves into cell
 Hypotonic Expansion- drink a lot of water, ECF expands and osmolarity
decreases, fluid goes to ICF
 o Hypertonic: cells shrink; osmolarity outside the cell is greater than inside the cell
so water moves out of cell
 Hypertonic Contraction- lose 1L with 100 mOsm, increases the osmolarity
making fluid from ICF go into ECF
 Hypertonic Expansion: give hypertonic saline/drink sea water, increases
the volume and osmolarity moving fluid from ICF to ECF

Fluid Homeostasis
 Intake- 2300mls
o Food/Fluid- 2100mls
o IV
o Metabolism- 200mls
 Absorption
o Gut
 Distribution
o Compartments
 Excretion- 2300mls
o Urine-1400mls
o Bowel- 100mls
o Lungs- 350mls
o Skin- 350mls

Excitable Membranes
 Simple reflex/myotatic reflex: receptor is activated – action potential occurs and repeats
itself across the axon to get to the neuron – enters central synapse – action potential goes
to output neuron – goes across axon – releases signal at the neuromuscular junction –
muscle contraction
 Axon/cell body- surrounded by plasma membrane, which is a lipid bilayer where each
lipid molecule is polar/amphipathic (one end of the molecule is charged (hydrophilic
head) and the other is neutral (hydrophobic tails)), that contains channels, pumps,
receptors, and its job is to separate ICF and ECF
o Because of the lipid bilayer, H2O and H2O molecules cannot get through the
membrane, therefore there are proteins to transport them
 Membrane proteins-
o Integral proteins- cannot be separated from the membrane without destroying;
have polar and non-polar regions
o Peripheral proteins- polar region, usually inside the cell, bound to integral
proteins
o Receptor proteins- bind transmitters that can alter membrane permeability/release
messenger molecules
o Ion channel proteins- can be gated or non-gated, allow certain ions to pass
o Carrier proteins- transport molecules across membrane

Membrane Transport Mechanism- how things get across the membrane

  Bulk flow: pressure; solute and solvent are moved across permeable membrane because
of pressure
 Simple diffusion: solutes move from high to low concentrations due to electrochemical
gradient; how lipid soluble the substance is will determine how easily it can diffuse;
diffusion will continue until solute concentration is equal on both sides of the membrane
o Current- depends on solute concentration gradient; >concentration gradient =
more solute diffuse across; greater the concentration, greater the current
 Simple facilitated diffusion: solutes move from high to low concentration due to
electrochemical gradient BUT they are transported
o Carrier- solute binds to the carrier and is transported across the membrane then
released on the other side
o Channel- solute passes through without dissolving in the membrane
o Characteristics of simple facilitated diffusion
 Specificity- ability to move one molecule or group of closely related
molecules
 Competition- can move several substrates, but they will compete with one
another
 Saturability- limited number of carriers, so eventually they will all be
bound up; which stops the increasing diffusion current
 Primary (traditional) active transport: transport is against electrochemical gradient;
requires energy from splitting ATP; transported molecule interacts with the carrier
(specificity, competition, saturability); energy is used
 Secondary Active Transport (Coupled/Facilitated Diffusion): two solutes on the same
side move across the membrane on the same carrier by facilitated diffusion; energy is
stored
o One solute moves up its electrochemical gradient
o One solute moves down its electrochemical gradient
o Energy is from the downhill solute moving from high to low concentration; the
energy was previously stored in the gradient and NOT made at the site of
transport
 Vesicular Transport: transports materials into or out of the cell with a vesicle
o Endocytosis: into the cell; a vesical in the cellular membrane is filled with
material from ECF and enters ICF
o Exocytosis: out of the cell; material is put in a vesicle that fuses to cellular
membrane and empties contents into ECF

Neurons:
 Motor neuron- transmitting information over distances (max 2m) using action potentials
 Action potential- brief change in internal electrical potential of the neuron; propagates
from one end of the axon to the other transmitting information in the process

Potentials
 Neurons, skeletal, cardiac, and smooth muscle all have a different potential inside
compared to outside the cell (polarized)
 Resting Potential: measured when there are no action or synaptic potentials
 o Inside the cell is between -5 to -100 millivolts (mV) (-30 smooth muscle; -90
skeletal/cardiac)
o Ease of ions crossing the membrane depend on cell properties and the different
ion concentration in ECF and ICF
 Permeability (Px)- measures how easily an ion can cross the membrane
o High permeability- easily crosses membrane; membrane potential is closer to
equilibrium potential
o Low permeability- difficult crossing membrane; membrane potential is farther
from equilibrium potential
o Semipermeable- some substances can cross easier than others
o Ex: Pna = 0 means no sodium can’t pass Pk >0 means potassium can get through
 Axon membrane is semipermeable, but impermeable to water and water soluble ions,
which need to cross with the help of integral proteins through channels, holes, or pores
that are usually filled with water so ions do not have to dissolve in the membrane’s lipid
interior
o Selective channels- allow particular ions to pass, rejecting others
 Aquaporin channel- selective channel that only allows water to pass
o Non-gated (leaky) channels- channels are constantly open and ions are free to
pass depending on concentration and voltage differences
o Gated channels- impermeable to all ions while closed, but permeable to some
when open; gates open and close due to:
 Mechanical stimulation- touch receptors
 Transmitter (ligands/synaptic channels)- bind to gated channel making it
open and close
 Voltage (action potential channels)- gated channels open and close in
response to voltage
 Drugs
 Anion- NEGATIVELY charged; attracted to anode (positive charge); ex: Cl-
 Cation- POSIVIVELY charged; attracted to cathode (negative charge); ex: Na+
 A- : organic anion that is the general term for large negative substances inside the cell;
ex: aspartate, acetate, pyruvate, phosphates, some proteins
o Negatively charged and too large to pass through any membrane channels
 Electrochemical gradient- difference in charge and ion concentration across the
membrane; can result in
o Membrane potentials
o Action potentials
o Synaptic potentials
o Electro and concentration gradient will become equal and opposite stopping the
net current
 Equilibrium potential- membrane potential when one ion gets through and one can’t; and
there is no net movement across membrane; if there are two ions in the cell that is what
the membrane potential will be
o Equilibrium potential is calculated by Nernst Equation: Ek=(RT/zF)ln(Ko/Ki);
which converts concentration gradient into electrical potential
 R- universal gas constant
  T- temperature
 Z- charge on the ion
 F- Faraday’s constant
 Ko- concentration outside of the cell
 Ki- concentration inside the cell

Action/Resting potentials
 Membrane permeability and Na-K ATPase pump determine where the resting potential is
 Ions move across membranes to try to bring the resting potential to their specific
equilibrium potentials
o Driving force- difference between the equilibrium potential and cell’s membrane
potential
 Driving force = membrane potential (current cell potential) – equilibrium
potential (where the ion wants membrane potential to be)
 Ex:
 Sodium: driving force = -90 - +66 = - 156; therefore there is a
large inward driving force; but the permeability for Na is low
 Potassium: driving force = -90 - -97 = +7; small outward desire
 Depolarization/decreasing membrane potential- increasing from resting potential
 Hyperpolarization/increasing membrane potential- decreasing from resting potential
 Membrane potential can be changed by
o Changing ion membrane permeability
o Changing ICF/ECF ionic concentrations
o Stimulation- injecting current into the cell
o Drugs- poison, anesthetics, psychoactives
 An action or synaptic potential occurs by changing the membrane’s permeability
 Na permeability is very low so there is not much influence on the resting potential

Established a baseline with resting potential- constant resting potential says nothing is happening
in the cell- to produce muscle contraction we need to change the resting potential

Action Potential
 Action potential is going to be the same amplitude every time
 Threshold- where stimulus reaches and the action potential will occur 50% of the time
 Cells that produce action potentials are excitable cells:
o Cardiac muscle (0.5 sec)
o Skeletal muscle (1-2ms)
o Neurons (0.5ms)
o Smooth muscle (some)
 ICF usually becomes positive at the peak of the action potential

Voltage gated Na and K channel

 Voltage gated Na+ channel has two gates closed at resting potential
o 1 gate opens when cell depolarizes
o 1 gate is open when cell is resting, slowly closes with depolarization
  Voltage gated K+ channel has one gate that is closed at resting potential
o 1 gate opens very slowly with depolarization

Action Potential
1. Sodium wants to go in but can’t because of low permeability
2. Stimulus hits
3. Causes depolarization
a. Sodium gate opens and other gate slowly starts to close
b. K+ gate slowly opens
4. Sodium rushes into cell- large + charge causing depolarization and the action potential
5. K+ channel near peak opens with high permeability and driving force high so outward
K+ current which helps repolarization; At peak of action potential Na starts to decrease
because driving force decreases; smaller inward Na+ current; driving force difference
between membrane potential and equilibrium potential
6. Na+ channels are closed with top gate open
7. K+ permeability is still high so K+ still leaving cell repolarizing toward resting potential
8. Na+ channel top channel is now closed, both gates are closed
9. Na+ lower (slow) gate reopens
10. Hyperpolarized to threshold
11. K+ channel closes gate
12. Back to resting potential

Effects of Local anesthetics- prevent voltage-gated sodium channels from opening with
depolarization, which means no action potential = no pain

 Refractory Period- time which new action potential is difficult or impossible

o Absolute- initiation of new action potential is impossible
 Beginning of action potential until partial repolarization
 During depolarization almost all Na+ channels are open so an extra
stimulus can’t open more
 During repolarization Na+ channels are inactivated and the slowly closing
gates are closed further stimulation will close them further
o Relative refractory- new action potential is possible with large amplitude
stimulation
 Occurs final stages of repolarization
 Na+ channels are partially reactivated, fast opening gates are closed but
some slowly closing gates have reopened
 Strong stimulation will get a smaller action potential
 Should not happen in the body, can happen in the heart
*Cell is repolarized by K+ leaving the cell

Permeability of Na+ controls AP

- Na+ permeability depends on a voltage-gated channel
- Na+ permeability controls membrane potential (voltage)
Voltage controls permeability; permeability controls voltage
- Depolarization opens more channels, which increases Na+ permeability, Na+ enters
increases cell – plus charge entering cell – increases depolarization which increases more
open channels
o Slow gate closes stopping the current breaking the link between current and
permeability
Inactivation/closing of Na+ channel does not repolarize the cell; to repolarize the cell have to get
rid of positive charge, so K+ leaves producing hyperpolarization making the gate closes

Sodium Potassium ATPase Pump does NOT repolarize the cell during the action potential it
maintains the gradient
 Determines the resting potential
o Na+ leaks in
o K+ leaks out
SOOOOOO
o Pump puts Na+ out of cell
o Pump puts K+ into cell
 Uses ATP to transport 3 Na+ out and 2 K+ in breaks down to ADP and Pi
 Ouabain- cardiac glycoside that inhibits pump activity to increase cardiac contractility

Action Potential Propagation-

1. Stimulus occurs, creating action potential
2. Na enters the cell producing depolarization
a. Na goes backwards to where it cannot get out, but K can
i. K leaves the cell causing hyperpolarization
b. Na goes forwards where it neutralizes the negative charges inside the cell causing
depolarization

 Conduction velocity- how soon a new action potential is created; depends on

o The charge: more charge the faster it is
o Current: how much inward current and current leaks there are
o Access the axon has
- All dependent on axion diameter and myelination
o Non-myelinated axon: entire axon is exposed to ECF, current from the first
action potential spreads causing depolarization and produces new action
potentials, but as current spreads, some leaks out of the axon through non-gated
leakage channels reducing the amount of depolarization
 The amount of current leaking out determines how far along the axon the
new action potential is generated
 The leaker the axon the closer the new action potential is to the
original and the slower the conduction velocity
 Velocity in nonmyelinated axon is proportional to the square root
of the radius: if you double the axon it will make faster conduction
o Myelinated axon: insulates the axon from the ECF, small gaps in the insulation
(nodes of Ranvier) expose the axon to ECF; increases the conduction velocity
  Action potentials are actively produced at the nodes of Ranvier
 Schwann cells- peripheral neuron that is a single myelin segment
around a single axon
 Oligodendrocytes- CNS neuron; forms multiple sheaths around
different axons
 Saltatory conduction- electrical impulse skips from node to node down the
length of an axon, speeding the conduction
 Conduction velocity still increases with the radius
 Because there aren’t as may leaky gates there is a decrease in the
work of the NA-K-ATPase pump and there doesn’t need to be as
much current

 Demyelinating Disease- immune system attacks myelin and you still get an action potential
but the current leaks out so the action potential may not move on; when the myelin is
destroyed, there are more K+ channels that cause an increase in hyperpolarization
o Can block action potential or can slow the conduction velocity
o Ex: Multiple sclerosis; Guillain-Barre syndrome

 At rest K+ dominates the membrane potential due to the high resting permeability
o K+ controls membrane potential at rest
 Action potential is produced by the conductance change and ion gradients
o Increased Na at high levels and slow output of K changes the potential
 During depolarization the sodium permeability controls the membrane potential
 During repolarization the potassium returns to controlling the membrane potential
 Throughout an action potential the concentration gradients remain constant

Review
 Water goes across the cell membrane to correct an osmotic imbalance
 Bulk flow: solute and solvent move because of pressure
 Simple diffusion: solutes move from high to low concentrations due to electrochemical
gradient
 Simple facilitated diffusion: solutes are transported from high to low concentration due
to electrochemical gradient
 Primary (traditional) active transport: transport ions against electrochemical gradient;
uses energy from splitting ATP
 Secondary Active Transport (Coupled/Facilitated Diffusion): two solutes are transported
across the membrane on the same carrier; stored energy is used
 Vesicular Transport: vesicles transport materials into or out of the cell
 The net driving force for an ion is the difference between concentration and electrical
gradients
o Na+ driving force: same- into cell
 Concentration is high outside and low inside (wants to go in)
  Electrical is high outside and low inside (wants to go in)
o K+ driving force: opposite- slight out of the cell
 Concentration is high inside and low outside (wants to go out)
 Electrical is high inside and low outside (wants to stay in)
 The membrane’s permeability to that ion determines how close the membrane potential is
to that particular ion’s equilibrium potential
 If KCl is increased in the ECF the K+ concentration gradient will decrease, K+ won’t be
leaving the cell but Na+ will be entering so there will be a significant depolarization
 If there is low K+ in the ECF the Na+ will enter as normal, but the concentration gradient
of K+ will increase causing hyperpolarization
o This can hinder an action potential from producing
 Diameter and myelination will increase the conduction velocity of an action potential