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wherein: k = Boltzmanns constant
T = temperature in degrees Kelvin
r = radius of the molecule
= viscosity of the medium
2. What equation relates permeability to diffusion coefficient? What is the relationship between
molecular radius and permeability?
The equation
, wherein: p = permeability;
K = partition coefficient (oil-water)
D = diffusion coefficient
X = membrane thickness
This equation relates permeability to diffusion coefficient. There is an inverse relationship between
molecular radius and permeability. Thus, as the molecular radius increases, both the diffusion
coefficient and permeability decrease.
3. What is the relationship between oil-water partition coefficient and permeability? What are the units
of the partition coefficient? How is the partition coefficient measured?
There is a direct relationship between oil-water partition coefficient and permeability. Thus, the
higher the partition coefficient of a solute, the higher its oil or lipid solubility and the more readily it
dissolves in a lipid bilayer. The units of the partition coefficient (K) are described as follows: if it involves
to immiscible liquids, K has no units; whereas if gas and a solution is involved, then appropriate units
must be used for partition. Example units for gas and a solution is Pamol-3. The partition coefficient is in
the formula:
[( )]
[( )]
Both concentrations must be of the same unit. Example, molarity, moldm-3, gdm-3, mgcm-3.
Osmotic Pressure
1. What is osmolarity, and how is it calculated?
Osmolarity is the osmotic pressure generated by the dissolved solute molecules in 1 liter of
solvent. Osmolarity (mOsm/L) = concentration(mmol/L) x number of dissociable particles.
2. What is osmosis? What is the driving force for osmosis?
Osmosis is the movement of water from greater water concentration to lesser water
concentration. The forces are hydrostatic pressure, the ability of water to move out of its compartment,
and osmotic pressure, which keeps water within the compartment.
3. What is osmotic pressure, and how is it calculated? What is effective osmotic pressure, and how is it
calculated?
Osmotic pressure is determined solely by the number of molecules in that solution. It is not
dependent on each factor as the size of the molecules, their mass, or their chemical nature. Osmotic
pressure (), measured in atmospheres (atm), is calculated by Vans Hoffs Law as = nCRT wherein:
n= number of dissociable particles per molecule
C = total solute concentration
R = gas constant
T = temperature in degrees Kelvin
Effective osmotic pressure involves both concentration of solute particles and the extent to
which solute crosses the membrane. The effective osmotic pressure is as follows:
wherein:
eff = effective osmotic pressure (atm)
g = number of particles/mol in solution
C = concentration (eg. mmol/L)
R = gas constant (0.082 Latm/mol K)
T = absolute temperature (K)
= reflection coefficient (no. units; varies from 0 to 1)
Case 1
Melvin Dizon is a 16-year old sprinter on the high school tract team. Recently after he completed his
events, he felt extremely weak, and his legs became like rubber. Eating, especially carbohydrates,
made him feel worse. After the most recent meet, he was unable to walk and had to be carried from the
track on a stretcher. His parents were very alarmed and made an appointment for Melvin to be
evaluated. As part of the workup, the pediatrician measured Melvins serum K+ concentration which
was normal (4.5mEq/L). However, because the pediatrician suspected a connection with K+, the
measurement was repeated immediately after a strenuous exercise treadmill test. After the treadmill
test, Melvins serum K+ was alarmingly low (2.2mEq/L). Melvin was diagnosed as having an inherited
disorder and subsequently was treated with K+ supplementation.
Questions:
1. What is the diagnosis for Melvins case?
Melvin has hypokalemia, a serum K+ concentration below normal (4.5mEq/L).
2. Propose a mechanism whereby a decrease in the serum K+ concentration could lead to skeletal
muscle weakness.
A decrease in serum K+ concentration (hypokalemia) can hyperpolarize skeletal muscle cells,
impairing their ability to develop the depolarization necessary for muscle contraction. It also reduces
blood flow to skeletal muscles.
3. Why did Melvins weakness occur after exercise? Why did eating carbohydrates exacerbate (worsen)
the weakness?
Due to the reduction of blood flow and hyperpolarized muscles, the body is weak. Plus,
exercising reinforces the status and potassium depletion of the body, which can also provoke
rhabdomyolysis. Also, hypokalemia has a dual effect on glucose regulation by decreasing insulin release
and peripheral insulin sensitivity, thus, worsening his condition more with carbohydrates and
carbohydrates are rich in glucose.
4. How would K+ supplementation be expected to improve Melvins condition?
Since his hypokalemia, which is below 4.5 mEq/L, is severe, intravenous potassium should be
given with maintaining follow up care. Another inherited disorder, called primary hyperkalemic periodic
paralysis, involves an initial period of spontaneous muscle contractions (spasms), followed by prolonged
muscle weakness. Using your knowledge of the ionic basis for the skeletal muscle action potential,
propose a mechanism whereby an increase in the serum K+ concentration could lead to spontaneous
contractions followed by prolonged weakness.
The initial period of spontaneous muscle contractions (spasms) is due to hyperkalemia. The
increase of K+ concentration makes the K+ equilibrium potential and resting membrane potential
become depolarized. Due to this, the resting membrane potential is closer to the threshold potential
and as a result, less inward current is required to initiate the upstroke of action potential.
There are two sets of Na+ channels: inactivation gates and activation gates. The activation gates
on Na+ channels open in response to depolarization. Although inactivation gates close slowly than
activation gates open, in prolonged depolarization as to hyperkalemia, the inactivation gates close and
remains closed when the inactivation gates are closed, the Na+ channels are closed, regardless of the
position of activation gates, action potential upstroke occur only if both sets of Na+ channels are open,
because the inactivated gates are closed, no action potential occurs. Thus, there is no muscle
contraction.