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Physiology 3120 Study Guide - Final Guide: Fluid Compartments, Extracellular Fluid, Facilitated Diffusion

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Tom Stavraky
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Physiology 3120 April Exam Notes
Body Fluids and Excitable Cells
Physiology is the study of function of the living
organism, and encompasses both normal and
pathological states.
The body can be divided into the internal and the
external environment. The external
environment is made up of the parts of the body
that are directly connected to the outside world
(i.e. the respiratory system, the GI system,
and urogenital tract). The internal
environment is basically the extracellular fluid,
including the blood and interstitial fluid; put
another way, the cells are “bathed in” the internal
environment. The intracellular fluid is part of
neither internal nor external environment.
Homeostasis is the act of maintaining relatively
stable internal conditions. It can be controlled by both the nervous system (responsible for
fast, minute-to-minute changes) and endocrine system (responsible for slower, long-term
changes), and is often maintained by a negative feedback mechanism. In this
mechanism, a set point is stored in the comparator (HYPOTHALAMUS) and sensors
(TEMPERATURE SENSORS) sense the current value of some controlled variable
(TEMPERATURE); if the current value varies from the set point, the comparator sends
signals to effector organs (VASCULAR SMOOTH MUSCLE CELLS) that causes a change that
brings the controlled variable back to the set point. It is this counteraction of change that
gives the mechanism its “negative feedback” name.
About 60% of any person is made up of water; this volume is referred to as total body
water (TBW). Intracellular fluid accounts for about 67% of TBW, whereas the ECF fluid
accounts for the remaining 33% (7% in plasma, 26% in interstitial fluid).
Because of the selective permeability of the cell
membrane, ion concentrations in the ICF and ECF differ.
Sodium (Na) is more concentrated in the ECF; potassium (K)
is more concentrated in the ICF; calcium (Ca) is more
concentrated in the ECF; and chloride (Cl) is more
concentrated in the ECF. These ionic distributions create a
chemical force that wants to move the ions down their
concentration gradients (e.g. Na in, K out).
The cell membrane itself is made up primarily of
phospholipids that are amphipathic (hydrophobic
at one end, hydrophilic at the other). Due to the
nonpolar inner layer, charged particles have difficulty
passing through the membrane, and because of the
small spaces between phospholipid molecules, large
molecules have the same difficulty. Membrane also
contains many membrane proteins that serve a
variety of functions, including transport, cytoskeletal
anchorage, catalysis, acting as receptors for ligands, and serving as antigens for cell
Although the cell membrane is useful in maintaining the ion concentration gradients,
substances still need to pass through the membrane into the cell. There are various
transport mechanisms that perform these functions
1. Simple diffusion

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This is the slowest and least efficient mechanism because it relies on the
random thermal motion of the molecules. The end result is a uniform
concentration throughout the medium as molecules move down their
concentration gradient. The reason this mechanism is so inefficient is that the
time required increases proportionally with the square of the distance, so
doubling the radius will increase the time required 4-fold.
2. Diffusion across cell membrane
In order to diffuse through the cell membrane directly, substances must be
nonpolar in order to pass through the hydrophobic interior; examples of
substances that use this route are O2, CO2, fatty acids, and steroids. The
driving force of this form is the concentration gradient of the substance,
and the rate is predicted by Fick’s first law of diffusion. The equation is
preceded by a negative sign because the substance moves from high to low
concentration, and therefore graphically will have a negative slope.
Diffusion rate (flux) INCREASES when: (1) concentration gradient
increases, (2) temperature increases, (3) total diffusion area increases,
(4) viscosity decreases, and (5) atomic radius decreases
Polar molecules cross the membrane by traversing through specialized pores
or channels (i.e. aquaporins, ion channels, etc.). Once again the driving force
is the concentration gradient, but movement is affected by a number of
factors: (1) size of the molecule, (2) charge on the molecule, (3) the size of
the concentration gradient, (4) the size of the pressure gradient, and (5)
hydration energy of the molecule because the hydration shell around ions
must be stripped off before passing through and this can only be done by its
specific channel/pore. Factors (1), (2) and (5) are filtering mechanisms in
that they prevent certain molecules from passing, but they are not the same
as the specificity mechanisms described below
3. Facilitated diffusion
A form of carrier-
mediated transport that
is used to transport
substances that can’t easily
cross the cell membrane
directly down their
concentration gradients.
The carriers, when bound to
the molecule of interest,
undergo a conformational
change to help the
molecules cross the
membrane. This form of transport (1) is specific, (2) shows saturability, and
(3) shows competitive inhibition.
4. Active transport
Another form of carrier-mediated
transport, but differs from facilitated
diffusion in that it requires energy (in the
form of ATP) to move substances against
their concentration gradients. It also
shows (1) specificity, (2) saturability, and (3)
competitive inhibition.
An example of a primary active
transport mechanism is the Na/K
ATPase, which moves 3 Na into the cell
and 2 K out of the cell for every ATP
molecule it hydrolyzes. Initially, 3 Na
bind to their intracellular binding sites;

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ATP is then hydrolyzed, and when the ADP is released, the Na are
pumped out of the cell. Then, 2 K attach to their extracellular binding
sites, and release of the Pi followed by attachment of a new ATP
molecule shuffles the K into the cell. This pump has a number of
functions, such as (1) maintaining concentration gradients, (2)
maintaining relatively high negativity inside the cell, and (3) prevents
the cell from swelling by pumping more ion out than in. This pump can
be inhibited by ouabain, digoxin/digitalis, or hypoxia.
Secondary active transport occurs when one molecule moves down
its concentration and the energy released is used to move another
molecule against its concentration gradient. The two molecules can
move in the same (symporter) or opposite (antiporter) directions,
and many physiological systems use secondary active transport to
absorb nutrients (i.e. Na/glucose symporter in the intestinal lumen)
and primary active transport to move nutrients into the blood and
maintain concentration gradients.
5. Osmosis is the movement of water down its concentration gradient
Water will move to where the osmolarity is the highest. Osmolarity is
defined as the number of osmotically active particles are present in a
given volume of solvent (for example, 1 mole of CaCl2 produces 3 osmoles
of osmotically active particles). Just as with movement of other particles, the
rate of osmosis is affected by the permeability of the membrane (must be
more permeable to water than to the solute[s]), the concentration gradient,
and the pressure gradient. The osmotic pressure is the pressure required to
counteract osmosis.
Tonicity is the ability of a solution to cause osmosis across a semi-permeable membrane.
The normal tonicity of bodily fluids is about 290-300 mOsmoles/kgwater. An isotonic
solution has the same osmolarity as the intracellular fluid (ICF) and therefore does not
cause osmosis; a hypotonic solution has a lower osmolarity than the ICF and therefore
cause osmosis INTO the cell; and a hypertonic solution has a higher osmolarity than
the ICF and therefore causes osmosis OUT OF the cell.
Fluid shifts may occur at the membrane in
response to ingestion of high water loads or
high salt loads. To visualize the changes in
volume and osmolarity that occur in the ICF
and ECF, use the Barrow-Yanet diagram.
In a water load the ECF initially
increases in volume and decreases
osmolarity. Water wants to move into
the cell to lower osmolarity in the ICF,
which causes an increase in ICF
volume and decrease in ICF
In a water loss, the ECF initially experiences a decrease in volume and increase in
osmolarity. Water wants to move out of the cell to lower osmolarity in the ECF,
which causes a decrease in ICF volume and increase in ICF osmolarity.
In a solute load, the ECF initially experiences an increase in both osmolarity and
volume. Water wants to move out of the cell to lower osmolarity in the ECF, which
causes a decrease in ICF volume and increase in ICF osmolarity.
In a solute loss, the ECF initially experiences a decrease in osmolarity but no
change in volume. Water wants to move into the cell to lower osmolarity in the ICF,
which causes an increase in ICF volume and a decrease in ICF osmolarity.
An isotonic NaCl load will increase the ECF volume, but will cause no osmosis.
Fluid shifts also occur between the plasma and the interstitial fluid (the Barrow-Yanet
diagram refers to fluid shifts between ICF and the interstitial fluid) take place at the
capillary endothelium, where there are 8nm slits through which almost everything
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