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Terminology

• A solute is a material that gets dissolved and is present in the smaller quantity of the solution
• A solvent is a material that does the dissolving
• A solution is a homogeneous mixture that consists of one or more solutes uniformly dispersed at the molecular or ionic level throughout a medium known as the solvent
• A homogeneous mixture means it's not possible to discern phase boundaries between the components of the mixture
• A phase boundary separates regions of a mixture where the chemical or physical properties of the mixture change
• Solutions aren't necessarily liquids; air is a solution of nitrogen, oxygen, and a few other minor components, and mixtures of oxygen and nitrous oxide are also solutions

Solution Concentrations

Molarity

• Molarity, also called molar concentration, consists of moles of solute per liter of solution
• Molarity is a common concentration unit in chemistry
• Molarity is abbreviated with a capital M
• Molar concentrations serve as conversion factors

Molality

• Molality, also known as molal concentration, expresses concentration in terms of moles of solute per kilogram of solvent
• It can be used as a conversion factor between moles of solute and kilograms of solvent
• Molality is abbreviated with a lowercase m
• In a laboratory, solutions are usually measured by volume, making molarity very convenient to employ for stoichiometric calculations
• Molarity is defined on moles of solute per liter of solution, making molarity dependent on the temperature of the solution
• Molar concentration decreases as temperature increases
• Molality finds application in physical chemistry, where it is often necessary to consider the quantities of solute and solvent separately rather than as a mixture
• Mass does not depend on temperature, so molality is not temperature dependent
• Molality is less convenient in analysis because quantities of a solution measured out by volume or mass in the laboratory include both the solute and the solvent
• When doing stoichiometry, molality requires an additional calculation
• Molality is never equal to molarity, but the difference becomes smaller as solutions become more dilute
• To convert between molarity and molality, we need to know the density of the solution

Percentages

• Percent by Weight to Volume (%w/v) is a percent of concentration in a clinical setting when measuring out a volume of medicine in a syringe
• It's defined as grams of solute per 100 ml of solution
• The first weight to volume process is useful as a conversion factor between grams of solute and milliliters of solution
• The second weight to volume process is useful to calculate the concentration of a material
• Percent by Weight (% w/w) - topical creams uses:
  • Exactly analogous to the definition of percent weight to volume, except the denominator expresses the quantity of solution in terms
  • To relate percent by weight to percent weight to volume, we need to employ the density of the solution
• Percent by Volume (% v/v) is never used in an analytical laboratory, because volumes are not additive

Normality

• An equivalent is analogous to a mole
• Normality is analogous to molarity for acids and bases
• One equivalent of a substance contains 1 mole of chemical reactivity
• Normality is equal to the equivalents of solute per liter of solution
• Unless the context of the chemistry is specified, normality is ambiguous

Parts Per Million

• The concentration of extremely dilute solutions is often expressed as parts per million
• A ppm concentration is analogous to a percent concentration
• A safe exposure concentration for any halogenated anesthetic agent is less than 2 parts per million (ppm) collected over a one-hour period, or 25 ppm of nitrous oxide over an 8-hour time weighted average, so 2 grams in a million grams of air
• When nitrous oxide is used in combination with halogenated gas, nitrous oxide to 25 ppm during anesthesia should aim to minimize concentrations of the halogenated gases to less than 0.5 ppm.
• 100% N2O = 1,000,000 ppm
• 1% N2O = 10,000 ppm
• 0.01% N2O = 100 ppm
• 0.0025% N2O = 25 ppm

Epinephrine

• Epinephrine concentration is measured differently:
  • A 1 mg ampule of 1:1000 epinephrine means that the solution contains 1 mg of epinephrine per ml
• Epinephrine is commercially available in two ampule sizes:
  • A 1 ml ampule containing 1 mg (i.e., 1:1000 or 1000 mcg per ml)
  • A 10 ml ampule containing 1 mg (i.e., 1:10,000 or 100 mcg per ml)
  • SO, 1:10,000 = 1 gram/10,000 = 1000 mg/10,000 or 1 mg/10 ml or 1000 mcg/10 ml = 100 mcg/ml
• OR a 1:100,000 solution contains 10 micrograms per ml
• OR a 1:200,000 solution contains 5 micrograms per ml
• OR a 1:400,000 solution contains 2.5 micrograms per ml
• Avoid in locations lacking collateral vessels - fingers, nose, toes, ears
• To prepare 25 ml of 2% lidocaine with 1:250,000 epinephrine:
  • An ampule of 1:1000 epinephrine (i.e., 1 mg/ml) must be acquired
  • 10 ml of saline to give 1:10,000 (i.e., 100 micrograms per ml) must be added
  • To this epinephrine solution, 1 ml must be added to 24 ml of 2% plain lidocaine. (i.e., 100 micrograms per 25 ml = 4 micrograms per ml)
• To prepare a 1:200,000 solution of epinephrine in 20 ml of 1% lidocaine:
  • Epinephrine must be acquired
  • 0.1 ml of epinephrine from a 1:1000 ampule must be taken and added to and add it to 19.9 ml of 1% plain lidocaine (100 mcg/20 ml = 5 mcg/ml)
• An epidural test dose most often consists of 3 ml of 1.5% lidocaine with 1:200,000 epinephrine

Solubility

• Some solutes are much more soluble in a given solvent than others
• The solubility of a solute is the amount of the solute that will dissolve in a given amount of solvent at a given temperature
• Increased water solubility allows medications to reach the bloodstream more quickly
• Factors affecting solubility can be intermolecular interactions between the substances, temperature, and pressure
• A medication able to form hydrogen, dipole-dipole, or ion-dipole and not covalent bonds will be more water-soluble (alkanes and alkenes cannot form hydrogen bonds with water)
• A saturated solution contains the maximum amount of a solute, as defined by its solubility
• A supersaturated solution contains more solute than allowed by the solubility of the solute
  • Not a stable system, because there is more solute dissolved in the sample than the solvent can accommodate
  • The excess solute will come out of solution, crystallizing as a solid, separating as a liquid, or bubbling out as a gas
• Two liquids are miscible if they are soluble in each other in all proportions
• Solubility is enhanced by intermolecular interactions between substances that have similar electron configurations, referred to as "Like dissolves like"
  • Polar solutes are more soluble in polar solvents, while nonpolar solutes are more soluble in nonpolar solvents
  • Salt (NaCl) solubility in water is an example as The similar polarity of water and salt's constituent parts promote dissolving.
• Substances like nitrogen, carbon dioxide, and oxygen are nonpolar and typically insoluble in a polar compound like water

Temperature

• Solid and liquid solutes in liquid solvents' solubility generally increases with increasing temperature (with a few exceptions)
• Gas solubility in liquids is inversely related to temperature:
  • As temperature increases, less gas is able to dissolve into a liquid
    • An increased temperature represents greater kinetic energy which allows dissolved gas molecules to escape and prevents further dissolving
  • Lower temperature slows the kinetic energy of gas molecules, allowing them to dissolve into liquids
• A clinical example of temperature affecting solubility is seen with a slower emergence of hypothermic patients receiving volatile agent general anesthetics.

Energy changes

• When a solute dissolves in a solvent, there is an associated energy change, and there is often times a noticeable change in the temperature of the solution (bond breakage).
• The energy change when using hot or cold packs is called the heat of solution or the enthalpy of solution: hsoln
• Defined as the energy change that accompanies dissolving exactly 1 mole of solute in a given solvent
• H (Enthalpy) is equal to the heat Q as long as the pressure remains constant.
• The energy change may be endothermic or exothermic
  • If the solution process is exothermic, energy flows out of the system (solvent and solute) into the surroundings, resulting in a temperature increase in the solution
  • If the solution process is endothermic, energy flows from the surroundings into the system, resulting in a temperature decrease in the solution
• Whether the heat of solution is endothermic or exothermic depends on the relative magnitudes of the lattice energy and the heat of solvation
• If tearing the ions apart requires more energy than is released by solvation, then Hsoln is going to be positive (endothermic) - consumes heat
• If the energy released by solvation is greater than the energy
• Energy is absorbed to break bonds which is an endothermic process, while energy is released when new bonds form which is an exothermic process
• Whether a reaction is endothermic or exothermic depends on the difference between the energy needed to break bonds and the energy released when new bonds form
• If more heat energy is released when making the bonds than was taken in, the reaction is exothermic; If more heat energy was taken in when making the bonds than was released, the reaction is endothermic
  • If the temperature increases with an endothermic reaction, it is essentially like adding more reactants to the system
  • If the temperature increases with an exothermic reaction, it is essentially like adding more products to the system
• Solubility of a solute decreases with increasing temperature if ∆Hsoln is negative (exothermic)
• Solubility of a solute increases with increasing temperature if ∆Hsoln is positive (endothermic)
• Le Châtelier's Principle states More reactants (endothermic) would favor a shift in the equilibrium to the right (products)
• More products (exothermic) will shift the equilibrium to the left (reactants)

Pressure

• As pressure increases, the solubility of a gaseous solute in a liquid solvent increases
• Since solids and liquids are not very compressible, pressure has very little effect on the solubility of solid and liquid solutes
• Gas solubility in a liquid is directly proportional to pressure and is described by Henry's law
  • The quantitative relationship between pressure and solubility is given by Henry's law: S = kHPgas
  • S = solubility, kH = Henry's law constant, and Pgas = partial pressure of the gas
• Henry's law main application in anesthesia pertains to calculating how much dissolved O2 and dissolved CO2 is in the blood
• Henry's law states that at constant temperature, the amount of gas that dissolves in a liquid is directly proportional to the partial pressure of the gas in the gas phase above gas-liquid interface (p=kc, p is pressure, k is Henry's constant, c is concentration)
• Overpressurizing is the process of significantly increasing the concentration of volatile anesthetic (partial pressure) delivered to a, patient to increase the alveolar concentration, thereby increasing the amount dissolved in the blood and speeding uptake
• The amount of O2 that dissolves in blood is 0.003 ml/100 ml blood/mmHg partial pressure.
  • To calculate the amount of O2 dissolved in the blood, multiply the partial pressure of O2 by 0.003
  • So, O2 dissolved in arterial blood when the PaO2 is 300 mmHg is 0.9 ml O2 /100 ml blood dissolved
  • The blood increase when the PaO2 increases from 100 to 500 mmHg is, 0.3 versus 1.5 ml O2 /100 ml blood dissolved or a difference of 1.2
  • If the inspired ml O2 is given, estimate the PaO2 by multiplying the inspired concentration by 5
  • FiO2 is 40%? 40 x 5 = 200 mmHg x 0.003 = 0.6 ml O2 /100 ml blood dissolved
  • The amount of CO2 that dissolves in blood is 0.067 ml/100 ml blood/mmHg where CO2 dissolved in arterial blood when PaCO2 is 50 mmHg is 50 x 0.067 = 3.35 ml CO2/100 ml blood

Colligative Properties of Solutions

• The vapor pressure of a liquid results from the most energetic molecules near the surface of the liquid escaping into the gas phase

• The likely escape sites for the liquid molecules are at or near the surface of the liquid

• As we begin to introduce solute molecules, some of these escape sites are occupied by the solute molecules, so fewer solvent molecules can escape into the gas phase

• Therefore, the vapor pressure of the solution is less than the vapor pressure of the pure solvent

• Raoult's law states the pressure of a volatile component of a solution (P) is equal times the mole fraction the pure substance (Po) with P = xPo

• Henry's law takes care of what happens IN the solution when you have gas over it, with Raoult's law looks at what is happening OVER the solution when you mix a non-volatile solute to a solvent that has a known vapor pressure when it's pure

• Boiling point is the temperature at which the vapor pressure of the material is equal to the ambient pressure

• The boiling point of a solution increases as the concentration of solute(s) increases, The change in boiling point is directly proportional to the molal concentration of the solute particles

• Freezing point is the temperature at which the liquid phase of the material is in equilibrium with the solid phase

• In order to enter into the solid state, the molecules (or ions or atoms) of the sample need to settle into an orderly, crystalline lattice structure

  • The presence of solute particles interferes with this process by getting in the way
  • It is necessary to cool the sample to lower temperatures, thereby lowering the kinetic energy of the molecules even further, before they will settle into the solid phase.

• Adding salt (or any solute) to water raises the boiling point

• Adding salt to water lowers the freezing point as well as raise its boiling point

• Diffusion is the net movement of one type of molecule through space as a result of random motion to minimize a concentration gradient with temperature directly proportional to kinetic energy

• Molecules with smaller mass diffuse faster as kinetic energy allows molecules to move freely in a fluid, and therefore mixtures of fluids tend to evenly distribute

• The velocity at which a molecule may distribute is determined by its molecular weight:

  • If the mass of a molecule is changed, there must be an opposite change in velocity Graham`s law:

• The rate of effusion (gas diffusion through an orifice) of a gas is inversely proportional to the square root of its molecular weight with r = 1/√mw where r is the rate of diffusion and mw is the molecular weight

• Graham's law describes the faster diffusion of smaller molecules compared to larger molecules

• Membrane thickness and molecular weight are inversely proportional to diffusion, while Concentration gradient, tissue area, and fluid tissue solubility are directly proportional to diffusion and Graham's law is helpful in understanding the effect of molecular weight on diffusion but is limited in fully describing all the factors influencing diffusion

Osmosis:

• Osmosis is the movement of water across a semipermeable membrane to equilibrate a concentration gradient
• The relative concentration of solutes in osmotic systems is called the tonicity
• Two solutions are isotonic if they contain equal concentrations of particles
• Entropy demands that osmosis occur between two solutions of unequal tonicity until the concentrations of the two solutions are equal
• Semipermeable membranes are permeable to water only and not to solutes
• Osmotic pressure is the force needed to stop osmosis from occurring
• Oncotic pressure is the osmotic pressure exerted by plasma proteins and electrolytes in capillaries (e.g., colloid osmotic pressure)
• Oncotic pressure balances the hydrostatic pressure tendency to push water out of capillaries with A normal oncotic pressure approximately as 28 mmHg
• The vascular system is a semipermeable membrane that responds to intravascular delivery of colloids by sequestering fluid
• Osmotic pressure (symbolized as capital pi, П) results from the potential drive for the concentration of water to equalize:
  • Osmotic pressure is a colligative property, and the osmotic pressure of a solution increases with increasing solute concentration
    • Albumin (MW is 69,000) does not penetrate the capillary wall and does provide osmotic pressure where albumin is the major determinant of intravascular volume
    • Most capillary walls are permeable to small solutes able and do not exert an osmotic effect

Diffusion and Anesthesia

• Diffusion is a passive process driven by entropy, where a gas or liquid will become uniform over time, and the diffusion rate varies depending the medium
• Fick's Law states that diffusion of a gas across a semipermeable membrane is directly proportional to the partial pressure gradient, the membrane solubility of the gas, and the membrane area, and is inversely proportional to the membrane thickness and the square root of the molecular weight of the gas.
  • Fick's Law can be used to determine the rate of diffusion, measure pulmonary gas exchange, to estimate gas exchange in COPD patients, cardiac output, the use of N2O to determine volume or pressure
• Nitrous oxide diffuses into air-filled cavities; therefore, delivery of nitrous oxide is contraindicated in patients with pneumothorax or where air-filled cavity expansion is undesirable
• Nitrous oxide expansion of endotracheal cuffs may cause tracheal mucosal damage where distention of the bowel during nitrous oxide delivery has also been documented
• Apneic oxygenation is well known and exemplifies the beneficial process of diffusion.
• Diffusion hypoxia results after the delivery of nitrous oxide is discontinued, and low inspired oxygen is administered
• Even though CO2 diffuses 22 times faster across the alveolar and capillary membranes than O2 because it is much more soluble in fluid than 02.
• Equilibration of an inhalational agent or any gas occurs everywhere in the body when the partial pressure of the gas is the same
• The process by which the fetus receives O2, and medications is simple diffusion
• Diffusion of a gas from alveoli to blood or the reverse requires a difference in partial pressure
• Main factors determining diffusion rate across membranes for non-gases is the concentration gradient for nonionized substances or electrochemical gradient for ions, lipid solubility, and size
• Agents that poorly penetrate the blood-brain barrier or placental barrier are lipid insoluble (ionized substances are lipid insoluble) and large (high molecular weights)
• Ions like Na do not penetrate lipid bilayers because ionized particles are hydrophilic and lipophobic

Colloids

• Colloids resemble solutions, the consist of one phase uniformly dispersed in a second phase. Examples: milk, blood, paint and jelly
• Colloids can occur in a particle size range of 10 nm to 200 nm, which is too large to produce a true solution from, ,as that size does not allow the individual constituents to form individual molecular bonds
• Colloidal solutions scatter light through particles large enough to display the Tyndall effect, while colloids are stable under a specific set of controlled circumstances