APPLIED CHEMISTRY, BIOCHEMISTRY, AND PHYSICS

I. BASIC SCIENCES

APPLIED CHEMISTRY, BIOCHEMISTRY, AND PHYSICS

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CHEMISTRY AND BIOCHEMISTRY

PHYSICS

NONPHARMACHOLOGY RELATED MATHEMATICS

QUESTIONS

Chemistry and Biochemistry

AQUEOUS SOLUTIONS AND CONCENTRATIONS

A solution in which water is the solvent is known as an aqueous solution.
- A dilute solution has a small solute to solvent ratio.
- A concentrated solution has a large solute to solvent ratio.
An aqueous solution is a homogeneous mixture of water, the solvent, and one or more other compounds (otherwise known as the solutes).
Solutes are the chemicals that dissolve in the water to form the solution.

The plasma concentration of a drug is the most practical measurement for monitoring the receptor concentration. The dose of a drug, the resulting plasma concentration, and the drug effect’s intensity are closely related

AMOUNT = CONCENTRATION X VOLUME

ACIDS, BASES, AND SALTS

Acids
- Produce hydrogen ions in aqueous solutions
- Are proton donors
- Are electron pair acceptors
Bases
- Produce hydroxide ion in aqueous solutions
- Are proton acceptors
- Are electron pair donors
Most of the acids and bases that are involved in acid-base regulation are weak acids and bases. Meaning, they have less tendency to dissociate their ions.
The normal H⁺ is 40 nEq/L. The normal pH is = -log (0.00000004), or 7.4
The normal pH of arterial blood is 7.4 and venous blood is 7.35. The reason for an acidotic venous pH is because of the extra amounts of carbon dioxide released from the tissues to form H₂CO₃.
When the pH falls below 7.4, the value is acidotic.
When the pH rises above 7.4, the value is alkalotic.
Three systems regulate the hydrogen ion concentration:
- Chemical acid-base buffer systems
  - The buffer systems react within a fraction of a second to adjust the pH. They are not responsible for eliminating hydrogen ions but merely “hide” them until balance is restored.
  - The bicarbonate buffer system is the most important extracellular buffer in the body.
- Respiratory center
  - Acts within minutes to eliminate carbon dioxide (and H₂CO₃)
- Kidneys
  - The slowest regulator of pH but is the most effective.
- Chemical acid-base buffer systems
  - Bicarbonate buffer system
    - The bicarbonate buffer consists of a water solution that contains two ingredients:
      - H₂CO₃, which is a weak acid
      - A bicarbonate salt like NaHCO₃

CARBONIC ANHYDRASE

CO₂ + H₂O <——————————-> H₂CO₃

Carbonic anhydrase is present in the lung alveoli and the epithelial cells of renal tubules.

H₂CO₃ <——————————> H⁺ + HCO₃^–

H₂CO₃ ionizes weakly to form small amounts of H⁺ and HCO₃^–

NaHCO₃ <————————–> Na⁺ + HCO₃^–

This is the second component of the buffering system, which is the bicarbonate salt.
The tendency of the buffering system is to decrease the CO₂ levels in the blood. This leads the respiratory system to decrease respiration and limits CO₂
The Henderson-Hasselbalch equation calculates the pH as long as the molar concentration of HCO₃^– and P_CO2 are known.
- Metabolic derangements are caused by bicarbonate concentration.
- Respiratory derangements are caused by carbon dioxide concentration.
Phosphate buffer system
- A major buffer for the renal tubular fluid and intracellular fluids.
Proteins
- Approximately 60 to 70 per cent of the total chemical buffering of the body fluids is inside the cells, and most of this results from the intracellular proteins.
Respiratory
- DIFFERENT WAYS TO SAY THE SAME THING:
  - When ventilation is increased, CO₂ is eliminated from the body, and this reduces the H⁺
  - The higher the alveolar ventilation, the lower the Pco2; conversely, the lower the alveolar ventilation rate, the higher the Pco2.
  - Respiratory control cannot return the H+ concentration all the way back to normal when a disturbance outside the respiratory system has altered pH.
  - WHEN BREATHING INCREASES, pH INCREASES (H⁺ DECREASES)
- THE LUNGS ARE THE INTERMEDIATE HELP… MEANING, THEY ARE NOT AS FAST AS THE CHEMICAL BUFFER SYSTEM BUT NOT AS SLOW AS THE KIDNEYS IN CORRECTING ACID-BASE IMBALANCE
  - The respiratory compensation for an increase in pH is not nearly as effective as the response to a marked reduction in pH.
  - Respiratory regulation of acid-base balance is a physiologic type of buffer system because it acts rapidly and keeps the H+ concentration from changing too much until the slowly responding kidneys can eliminate the imbalance.
- About 1.2 mol/ L of dissolved CO2 normally is in the extracellular fluid, corresponding to a Pco2 of 40 mm Hg.
- The respiratory system is a negative feedback for H⁺ concentration and pH.
Renal
- The kidneys control acid-base balance by excreting either an acidic or a basic urine.
- The primary mechanism for removal of nonvolatile acids from the body is renal excretion. They are referred to as nonvolatile because they are not H₂CO₃ and cannot be exhaled by the lungs.
- The kidneys also filter and reabsorb bicarbonate which conserves the primary buffer system of the extracellular fluid.
- The kidneys regulate extracellular fluid H+ concentration through three fundamental mechanisms:
  - Secretion of H+
  - Reabsorption of filtered HCO3-
  - Production of new HCO3-
- 85% of HCO₃^– is reabsorbed in the proximal tubule. The remaining is absorbed in the thick ascending loop of Henle and the remaining in the collecting duct.
Phosphate and ammonia combine with excess H⁺ to form new HCO₃^– in the kidneys.
Examples
- OPPOSITES ATTRACT
  - Ionic compounds are formed by oppositely charged ions/compounds.
    - Sodium (Na⁺) routinely combines with chloride (Cl^–) to for a salt NaCl.
    - Morphine is a weak base, so the anion sulfate (SO₄^2-) combines with it to form a salt.
    - Lidocaine is a weak base and combines with hydrochloride (HCl^–).
    - Thiopental is a weak acid because it combines with the cation sodium (Na⁺) to form sodium thiopental.
  - Ionization
    - The pKa is a measure of the strength of a compound’s interaction with a proton (H⁺). The lower the pKa, the more acidic it is. The higher the pKa, the more basic it is.
    - The pKa value means half of the compound is ionized (hydrophilic) and the other half is nonionized (lipophilic).
    - Ions carry a charge and is hydrophilic so it’s not able to cross the lipid membrane. The more of the compound that is available in the lipophilic (nonionized form), the easier it is able to cross the lipid membrane and exert its effect.
    - A conjugate acid is the species that remains after a base gains a proton, and a conjugate base is thespecies that remains after an acid loses a proton.
  - Isomers
    - Enantiomers (substances of opposite shape) are a pair of molecules existing in two forms that are mirror images of one another.
    - These enantiomers are differentiated by how that rotate polarized light, meaning clockwise (dextrorotatory) or counterclockwise (levorotatory). When the mixture of enantiomers is equal, it is called a racemic mixture and the polarized light does not rotate.

CHEMICAL REACTIONS: OXIDATION, REDUCTION, HYDROLYSIS, AND CONJUGATION

The main organ for drug metabolism is the liver, even though metabolism can occur in the plasma, lungs, GI tract, kidneys, heart, brain, and skin. The goal of metabolism is to change lipid-soluble agents into more water-soluble forms so the kidneys can eliminate them. Drug metabolism occurs in two phases. Phase 1 are oxidation, reduction, and hydrolysis reactions and generally result in increased polarity of the molecule, transforming a lipid-soluble compound to a water-soluble one. Phase 2 reactions involve conjugation reactions, in which a drug or metabolite is conjugated with an endogenous substrate such as glucuronic, sulfonic, or acetic acid.
- Phase 1
  - Oxidation involve adding oxygen to the molecule or increasing the oxygen content. These enzymes are catalyzed by the cytochrome P-450 system.
  - Reduction involves the gain of electrons and also the cytochrome P-450 system.
  - Hydrolysis is adding water to an ester or amide to break the bond and create two smaller molecules.
    - Examples: pseudocholinesterase (succinylcholine, cocaine, procaine, neostigmine) and nonspecific esterases (remifentanil, atracurium, cisatracurium, esmolol)
  - Phase 1 make the compounds or molecules more water-soluble so that the kidneys can excrete them easier. Also, phase 1 helps prepare these molecules for phase 2 reactions.
- Phase 2
  - Conjugation involves adding glucuronic acid, sulfuric acid, glycine, acetic acid, or a methyl group to form a new compound.
  - Leads to a more polar compound that is highly ionized and more easily removed by the kidneys.

METABOLISM

Carbohydrates
- The final products of carbohydrate digestion are glucose, fructose, and galactose; glucose makes up 80%. Even then, the liver converts most of the remaining monosaccharides into glucose.
- Glucose cannot readily pass through the cell membrane’s pores because the molecular weight is 180 (particles with a molecular weight of 100 can readily pass). Through facilitated diffusion and active sodium-glucose co-transport, glucose is delivered to the cells.
- In the presence of insulin, glucose transport into most cells increases by 10 times.
- Upon entering the cell, glucose is almost immediately phosphorylated so that it remains in the cell for use and is called glucose-6-phosphate. This phosphorylation is almost completely irreversible except in the liver, renal tubular epithelial cells, and the intestinal epithelial cells because these contain the enzyme glucose phosphatase. Glucose phosphatase can reverse the reaction when needed.
- Glucose is converted into glycogen in a process called glycogenesis. This is done primarily in the liver and muscle cells. The conversion allows for future use of glucose for energy.
- Glycogenolysis is the process where glycogen is phosphorylated, or broken down, by glucose phosphate and converted to glucose for energy.
- The phosphorylase enzyme is inactive during rest but is activated by two enzymes, epinephrine and glucagon. Both of these hormones work by forming cyclin AMP and then leads to phosphorylation.
  - Epinephrine is released by the adrenal medulla when the sympathetic nervous system is stimulated.
  - Glucagon is a hormone that is secreted by the alpha cells of the pancreas when blood glucose levels fall.
- The process of splitting the glucose molecule into two molecules of pyruvic acid is called glycolysis. The two pyruvic acid molecules combine with coenzyme A to yield Acetyl-CoA, 2 carbon dioxide molecules, and 4 hydrogen molecules. The next stage of glucose degradation is the Kreb’s cycle, which takes place in the mitochondria. The 4 hydrogen atoms from glycolysis, 4 hydrogen atoms yielded during the formation of acetyl CoA from pyruvic acid, and 16 in the Kreb’s cycle (24 total) are then combined with nicotinamide adenine dinucleotide (NAD⁺) to form tremendous quantities of ATP.
- Only 2 ATP molecules from glycolysis and 2 from the Kreb’s cycle are yielded. 90% of the total ATP is created by oxidative phosphorylation. ADP is converted to ATP by adding a free ionic phosphate radical.
- For each glucose molecule that is broken down, 38 moles of ATP is yielded. Specifically:
  - A net gain of 2 from glycolysis (4 are made but 2 expended for phosphorylation)
  - 2 moles of ATP from Kreb’s cycle
  - 30 ATP moles from the 24 hydrogen atoms that are released
  - 4 more from chemiosmotic oxidative schema in the mitochondria
- 66% maximum efficiency for energy transfer and the remaining 34% of the calories stored from these processes become heat and are lost.
- Anaerobic energy means energy that can be derived from foods without the simultaneous utilization of oxygen; aerobic energy means energy that can be derived from foods only by oxidative metabolism. Carbohydrates are the only significant foods that can be used to provide energy without the utilization of oxygen; this energy release occurs during glycolytic breakdown of glucose or glycogen to pyruvic acid. For each mole of glucose that is split into pyruvic acid, 2 moles of ATP are formed.
- In times of insufficient oxygen, energy can still be released because the breakdown of glucose to pyruvic acid does not require oxygen. This is termed anaerobic energy. The process of anaerobic energy is wasteful of glucose in that only 3% is metabolized for energy. As the metabolic end products buildup from glycolysis, lactic acid forms in the absence of oxygen. It can rapidly be reconverted to pyruvic acid when oxygen is available so that the energy is not lost. The organ most responsible for this conversion is the liver.
- The heart is also capable of converting lactic acid to pyruvic acid for energy.
- Pentose phosphate pathway is a 2^nd way to breakdown and oxidize glucose. It makes up 30% of the glucose breakdown but even more in fat cells. The hydrogen that is released during the pentose phosphate pathway combines with NADP⁺. This is important because NADPH is used for the synthesis of fats from carbohydrates.
- The liver and muscle cells store enough glycogen for up to 24 hours, the remaining glucose is converted to fat.
- Gluconeogenesis is the process of converting amino acids and the glycerol portion of fat into glucose when carbohydrate stores are low. In the presence of low circulating carbohydrates, the anterior pituitary (adenohypophysis) secretes corticotropin which stimulates the adrenal cortex to produce cortisol. Cortisol is responsible for mobilizing proteins so that amino acids can be used in gluconeogenesis.
Lipid
- The first stage in the hydrolysis of triglycerides yields fatty acids and glycerol. They are then transported to tissues for oxidation for energy. Only brain tissue and RBCs cannot use fatty acids for energy.
- As is the case for glycolysis, lipid degradation and oxidation can only occur in the mitochondria, primarily in the liver.
- Beta oxidation is the process by which the fatty acid molecule releases acetyl coenzyme A (acetyl-CoA).
- The acetyl-CoA molecules formed by beta-oxidation of fatty acids enter into the Kreb’s cycle. The acetyl-CoA from fatty acids is the same as the acetyl-CoA formed from pyruvic acid in glycolysis.

CELLULAR MECHANISMS OF ACTION/ DRUG RECEPTOR INTERACTION

The smaller the molecular size of an agent, the better it crosses the lipid barriers and membranes of tissues. Transport across the membranes can occur due to active or passive transport. Active requires energy and is quicker. Passive transport does not require energy and transfers molecules from a high concentration to a low concentration.
Acids and bases exist in solutions in both ionized and nonionized forms. The ionized form is water soluble and the nonionized form is lipid soluble. Nonionized molecules are lipid soluble and therefore can penetrate cell membranes. Ionized molecules cannot.
The pK_a helps determine the dissociation of an agent at a particular site and its pH across the membrane. When the pK_a of an agent is equal to the pH, the ionized and nonionized forms are in equal concentrations.
There are two forms of endocytosis: pinocytosis and phagocytosis.
- Pinocytosis occurs when a small amount of particles is ingested that forms vesicles of extracellular fluid and particulate constituents inside the cell cytoplasm.
- Phagocytosis is the ingestion of large particles, like bacteria or whole cells.
All the respiratory passages, from the nose to the terminal bronchioles, are kept moist by a layer of mucus that coats the entire surface. The mucus is secreted partly by individual mucous goblet cells in the epithelial lining of the passages and partly by small submucosal glands.
Goblet cells function mainly in response to local irritation of the epithelium; they extrude mucus directly onto the epithelial surface to act as a lubricant that also protects the surfaces from excoriation and digestion in the GI tract.
Ciliary movement occurs only on the inside of the airway and fallopian tubes of the reproductive tract. In the nasal cavity and lower respiratory airways, the whiplike motion of cilia causes a layer of mucus to move at a rate of about 1 cm/min toward the pharynx, in this way continually clearing these passageways of mucus and particles that have become trapped in the mucus. In the uterine tubes, the cilia cause slow movement of fluid from the ostium of the uterine tube toward the uterus cavity; this movement of fluid transports the ovum from the ovary to the uterus.
GUYTON
Receptors
- The drug-response equation is fundamental to pharmacological principles. It is derived from the law of mass action.
- Law of mass action: At steady state, equilibrium exists between bound and unbound drug receptors and the concentration of free unbound drug at the site. The higher the concentration of free unbound drug or the higher the concentration of unbound receptor lends the higher likelihood of the formation of the drug-receptor complex.
- NAGELHOUT
- Receptor classification:
  - G protein-coupled receptors
  - Ion channels
  - Catalytic receptors
  - Nuclear hormone receptors
  - Transporters
  - Enzymes
  - Other protein targets
- Receptor types:
  - GABA
  - Opioid
  - Alpha
  - Beta
  - Acetylcholine
  - Histamine subtypes
  - Pain-related capsaicin receptor
  - Nicotinic
  - Muscarinic
  - Others
- Voltage-sensitive ion channels represent the classic ion channels like sodium, potassium, chloride, and calcium. These are present in neurons, skeletal muscles, and endocrine cells. At rest, the membrane potential is closed (-60 to -80 mV). When the cell membrane depolarizes (becomes less negative), an action potential occurs that allows the channel to open and ions to pass.
- Ligand-gated ion channels open and close in response to changes in the presence of extracellular ligands (neurotransmitters) and are involved primarily in fast synaptic transmission between excitable cells. Specific neurotransmitters bind to these receptors and transiently open or close the associated ion channels in the absence of second messengers to alter ion permeability of the plasma membranes and thus membrane potentials. STOELTING PHARMACOLOGY
  - Acetylcholine (nAChRs) and serotonin (5HT₃) are cation-selective and excitatory
  - Gamma-aminobutyric acid (GABA) and glycine are anion-selective and inhibitory
  - Ligand examples in anesthesia:
    - Neuromuscular blockers
    - Barbiturates
    - Benzodiazepines
    - Ketamine
  - Transmembrane receptors interact selectively with extracellular compounds to begin a process of biochemical changes for an intended pharmacologic or physiologic response.
  - Current understanding of molecular pharmacology suggests that the delay recorded from initial drug administration to the onset of the tissue response reflects the time required for molecular orientation and attachment to the receptor.
  - IV anesthetics act by binding to membrane receptor channel proteins.
  - Inhalation anesthetics have long been thought to produce their anesthetic action by dissolving in the lipid bilayer surrounding membrane ion channels and interfering with their ability to open and close.
  - Some endogenous proteins provide alternative drug-binding sites. These sites are more correctly termed acceptors; the acceptor reduces the amount of unbound drug available for receptor complexing.
    - Albumin generally binds to acidic drugs
    - Alpha1-acid glycoprotein and beta-globulin bind basic drugs
  - There are four concepts derived from a dose-response relationship:
    - Potency
    - Efficacy
    - Variability
    - Slope
  - Transduction
    - Signal transducers are surface receptor proteins that bind extracellular signaling molecules and convert this information into intracellular signals that alter target cell function. G protein-coupled receptors interact with specific guanine nucleotide proteins in plasma membranes which in turn activates or inhibits enzymes or ion channels. A hallmark of signal transduction by G protein-coupled receptors is their ability to amplify extracellular signals. Enzyme linked cell surface receptors are a heterogeneous group of receptors that are associated with intracellular enzymes (tyrosine kinases, guanylate cyclases) and receptor binding activates intrinsic catalytic activity.

2^nd messenger	Target responses	Examples
Cyclic adenosine monophosphate (cAMP)	Release protein kinases, beta-receptor stimulation of energy release, inotropic and chronotropic cardiac effects, production of adrenal and sex steroids, and other endocrine and neural processes	Catecholamines, caffeine, milrinone
Phosphoinositides and calcium	Activate calmodulin	Lithium
Cyclic guanosine monophosphate (cGMP)	Activate protein kinases	Nitroglycerin and sodium nitroprusside

ATP is converted to cAMP by adenylate cyclase, which is an intracellular enzyme.
Phosphodiesterases (PDEs) are enzymes that regulate levels of cAMP and cGMP in the cell.
Nitric oxide is synthesized in endothelial cells from the amino acid L-arginine by a family of calcium-activated enzymes known as NO synthases. As a gas, NO diffuses from the producing cells into target cells, where it activates guanylate cyclase to increase the cGMP concentration, which in turn results in vasodilation.

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Physics

UNITS OF MEASUREMENT

1 mm Hg = 1.36 cm H₂O
1 atm = 760 mm Hg = 14.7 psi = 101 kPa = 1 bar
1 psi = 54 mm Hg

Gases and Gas Laws

Law of Laplace
- The tension in the left ventricular wall during diastole increases.
Ohm’s law
- The equation for calculating systemic vascular resistance (SVR) is: 80 x SVR = (MAP – CVP)/CO, where MAP is mean arterial pressure, CVP is central venous pressure, and CO is cardiac output.
Le Chatelier’s principle
Superimposition principle
Bernoulli’s principle
Joule-Thompson effect
- Ice crystals forms on a cylinder releasing a compound gas.
Frank-Starling’s law
- The greater the tension in the ventricular wall at end-diastole, the greater the stroke volume.
Bohr effect
Henry’s law
- Used to calculate the amount of oxygen and carbon dioxide dissolved in the blood.
- O₂ dissolved = PO₂ x 0.003
- CO₂ dissolved = 0.067 x PCO₂
Dalton’s law
- Permits the calculation of the concentration percentage of a gas by dividing the partial pressure of the gas by the total pressure.
- Partial pressure calculation
Fick’s law
- The amount of gas that diffuses is directly proportional to:
  - Partial pressure difference of the gas across the membrane.
  - Membrane area
  - Gas solubility in the membrane
- The amount of gas that diffuses is indirectly proportional to:
  - Membrane thickness
  - Square root of the molecular weight of the gas
- When nitrous oxide is turned on, gas bubbles expand.
- Nitrous oxide is 34 times more soluble in blood than nitrogen.
- Diffusion hypoxia; concentration effect; second gas effect
- Diffusion is proportional to solubility.
Fick’s principle
- The Fick principle states that the amount of oxygen consumed equals the difference between arterial and mixed venous oxygen content multiplied by the cardiac output.
Poiseuille’s law
Van der Waal’s effect
- Gas molecules occupy volume and attract and repel each other.
Avogadro’s hypothesis
- Avogadro’s number is 6.02 x 10²³, or the number of molecules in one mole of a substance.
- One mole of gas at standard temperature and standard pressure occupies a volume of 22.4 L.
- One-half mole of oxygen occupies 11.2 L under standard conditions.
Boyle’s law
- The volume of a given mass of an ideal gas is inversely proportional to the pressure, provided that the temperature remains constant.
- A full E-cylinder of oxygen will empty 625-675 liters into the atmosphere.
- Explains normal tidal breathing.
- Squeezing an ambu-bag.
- Volume of gas released into the atmosphere from an O2 tank.
Charles’ law
- Volume is directly proportional to the absolute temperature at constant pressure.
- The cuff of an LMA expands in the autoclave.
Gay-Lussac’s law
- Pressure is directly proportional to absolute temperature if volume is constant.
Ideal gas law
- PV = nRT
  - P- pressure
  - V- volume
  - n- number of moles of gas
  - R- universal gas constant
  - T- absolute temperature
- Reynold’s number
  - Fluid velocity
  - Fluid viscosity
  - Tube diameter
- Beer’s law
  - Pulse oximeter
- Graham’s law
  - Helium will diffuse faster than oxygen.
- Vapor pressure is a function of temperature.
- Relative humidity
  - The ratio of the water vapor amount in the air to the maximum water vapor amount the air can hold at the same temperature.
- Density
  - The ratio of the mass of an object to its volume.
- Critical pressure
- Boiling point
  - Temperature at which the vapor pressure equals atmospheric pressure.
- Latent heat of vaporization
  - The amount of energy required to convert a liquid into a gas with constant temperature.
  - The latent heat of vaporization is more precisely defined as the number of calories required to change 1 g of liquid into vapor without a temperature change.
- A mass spectrometer measures the concentrations of inhaled agents by measuring molecular weight.

Solubility, Diffusion, and Osmosis

Graham’s law
- Helium will diffuse faster than oxygen.

Pressure and Fluid Flow

Reynold’s number
- Fluid velocity
- Fluid viscosity (inversely related)
- Tube diameter
When Reynold’s number exceeds 1500-2000, turbulent flow exists.
Resistance is dependent upon the viscosity of oxygen during normal laminar airflow

ELECTRICITY AND ELECTRICAL SAFETY

Ohm’s law: E (electromotive force, in volts) = I (current, in amperes) x R (resistance, in ohms)
This law is the basis for: BP = CO X SVR
A conductor permits the flow of electrons. When the flow is in the same direction, it’s known as direct current (DC). When the electron flow reverses direction regularly, it is known as alternating current (AC).
An insulator is something that opposes the electron flow.
Two parallel conductors that are separated by an insulator is a capacitor. Capacitance refers to how much a substance can store a charge.
Inductance is a property of AC circuits in which an opposing electromotive force can be electromagnetically generated in the circuit.
Electrical shocks occur when an individual completes the electrical circuit. Damage can occur in 2 ways:
- Normal electrical cellular function can be damaged (brain function, breathing, heart rhythm, etc.
- Electrical, or thermal, burns from the electricity that entered the body and dissipated through tissues.
The severity of the shock is determined by current (amps) and the duration of the current flow. Power companies maintain the line voltage constant at 120 V.
Electrical shock is divided into two categories:
- Macroshock– large amounts of current flowing through an individual that can cause harm or death. The current is conducted through all tissues of the body according to their conductivity. Meaning, the density of the current is not as intense as the charge that contacted the skin surface.
- Microshock– electrically susceptible individual who has an external conduit that is in direct contact with the heart. E.g. pacing wires and central venous pressure catheter.
The power that is used in the operating room is usually ungrounded, which means the current is isolated from the ground potential. This provides a layer of protection due to the conditions of the OR, that is, multiple electronic devices, power cords, fluids, puddles, etc.
The ungrounded power is supplied by an isolation transformer. This power is isolated from the ground and the wires are known as line 1 and line 2.
So, with ungrounded electrical power, an individual will only receive a shock if lines 1 and 2 are contacted. This is contrasted to grounded electrical power where the “hot” line is contacted and the person’s feet on the ground complete the circuit.
The line isolation monitor (LIM) is a device that continuously monitors the integrity of an isolated power system (IPS).
LIMs alarm when the impedance falls below 60,000 ohms on either side of the IPS. This does not necessarily mean a dangerous situation, only that the system is no longer isolated from the ground. The alarm is triggered differently according to the generation:
- 1^st generation- alarms at 2 mA but could not isolate the faulty line
- 2^nd generation- alarms at 2 mA was able to isolate the faulty but could interfere with physiologic monitoring
- 3^rd generation- bypassed the “false” alarms by alarming at 5 mA and addressed the prior generations’ issues.
Microshock, as previously stated, occurs when a small current has a direct path to the heart but produces a large current density and will cause ventricular fibrillation. The line isolation monitor does not provide protection from microshock.
Electrosurgical units (ESU), like a Bovie, generate high-frequency currents between 500,000 to 1 million Hz. These very high-frequency currents have a low tissue penetration and do not excite contractile cells (meaning it won’t cause ventricular fibrillation).
Do not be confused by electrocautery and electrosurgery. Electrocautery is a small, handheld, battery operated device that uses an electrical current to heat a metal wire for cauterization of tissues.
Bipolar ESU is different from unipolar in that the current passes only between the two blades of a pair of forceps. Bipolar ESUs generate much less power than unipolar.
For the patient that presents for surgery with automatic implantable cardioverter defibrillator (AICD), they are at risk of ventricular fibrillation caused by electrical interference. The use of unipolar ESU and electroconvulsive therapy are both capable of triggering a defibrillation pulse in patients with an AICD. The device should be shut off with a magnet. For the patient with an AICD, an external defibrillator and a noninvasive pacemaker should be in the OR.
Fire prevention is best accomplished when the “fire triad” is prevented from coming together at the same time (heat/ignition, fuel, and oxidizer). Communication is KEY in preventing OR fires because, often, a different individual is responsible for each of the limbs of the fire triad (OR nurse- fuel source; anesthesia- oxidizer; surgeon- ignition source).
The most common OR fire occurs involve a head/neck surgery under regional or MAC anesthesia where high oxygen flows are used. FiO₂ is important as well; lowering the oxygen content decreases the likelihood of ignition.
Airway fires can occur during laser surgery and the tracheal tube will act as a blowtorch to the lungs during ventilation.
- “Laser-resistant” tracheal tubes should be used during these surgeries. LaserFlex is an option during laser surgery that utilizes CO₂ This tube has two cuffs that can be inflated with methylene blue so that the surgeon can see when one of the cuffs has been ruptured.
- The Lasertubus can be used for the Nd:YAG laser. It has a soft rubber shaft that is covered by a corrugated silver foil and that is covered in a Merocel sponge jacket. The Merocel must be kept moist with saline.

REFERENCE: Ehrenwerth et al. Anesthesia Equipment: Principles and Applications 3^rd edition, pages 526-555

VAPORIZATION AND HUMIDIFICATION

Dalton’s law states that the total pressure of a mixture of gases is equal to the sum of the pressure of each individual gas. The partial pressure is EQUAL to the fractional concentration MULTIPLIED BY the total pressure.
Humidity is the moisture content of the atmosphere. It is also the water present as a vapor in a gas mixture.
Vapor describes the gaseous state of a substance that appears ordinarily as a liquid or solid. Vapor pressure can be described as the amount of gas and liquid molecules of a substance in equilibrium at a specific temperature.
For a substance to change from a liquid to a gas, a certain amount of energy is required to overcome the force that binds them together in the liquid state. This force is known as van der Waals. The specific amount of heat is referred to as the latent heat of vaporization of a substance.
Evaporation is when a liquid changes to a gas at a temperature that is below the boiling point.
At a substance’s boiling point, the vapor pressure of a liquid is equal to the atmospheric pressure. For example, water’s vapor pressure at 100^oC is 760 mm Hg.
Humidity can be further discussed in terms of absolute humidity and relative humidity.
- Absolute humidity is the mass of water vapor per unit volume of the gas mixture.
- Relative humidity refers to the ratio of the actual water vapor content of the gas mixture to its total capacity at the given temperature.
The amount of water vapor a gas can contain is directly proportional to the temperature of the gas.

When a liquid turns into a gas, the temperature of the liquid decreases. This is vaporization. This flow of energy from a warmer area to the cooler area is called heat.

MEASUREMENT OF OXYGEN, CARBON DIOXIDE, AND HYDROGEN IONS

Gas sampling systems can be non-diverting/mainstream analyzers or sidestream/diverting systems. Quantification of gas molecules occurs by infrared radiation of each atom. The infrared (IR) analyzer measures partial pressure.
- For the non-diverting or mainstream analyzers, gas passes the analyzer interface which is in the main gas stream. Waste gas scavenging is not necessary for these systems.
- Sidestream or diverting systems are more commonly used because they are more versatile. The gas from the breathing circuit is continually drawn by an adapter between the circuit and patient’s airway (Y-piece).
Mass spectrometry separates the molecular component of a gas mixture and determines the proportion of each gas.
Henry’s law states the amount of a given gas dissolved in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid.
- The amount of O₂ that dissolves in blood is 0.003 mL/100 mL blood. To obtain the amount of O₂that is dissolved in blood, the partial pressure of O₂ must be multiplied by 0.003.
- The amount of CO₂ that dissolves in blood is 0.067 mL/100 mL blood. To obtain the amount of CO₂ that is dissolved in blood, the partial pressure of CO₂ must be multiplied by 0.067.
Beer-Lambert law
- The absorbance of a light-absorbing material is directly proportional to its concentration in solution and the path length through which the light travels.
- Pulse oximetry utilizes these laws.
- Capnography also relies on these laws.
The normal H⁺ is 40 nEq/L. The normal pH is = -log (0.00000004), or 7.4 The normal pH of arterial blood is 7.4.

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Nonpharmacology Related Mathematics

Non-Pharmacology Related Math

Dalton’s law
- Permits the calculation of the concentration percentage of a gas by dividing the partial pressure of the gas by the total pressure.

4-2-1 Maintenance Fluid

Body weight (in kg)	Hourly fluid rate (in mL/kg)
0-10	4
11-20	2
> 20	1

Examples
- Patient weighs 66 kg. What is the hourly fluid requirement?
  - First 10 kg = 40 mL/hr
  - Next 10 kg = 20 mL/hr
  - Last 46 kg = 46 mL/hr
    - = 106 mL/hr
  - If the patient’s weight in kg is > 40 kg, the hourly fluid requirement will be 40 PLUS their weight. MEANING, the same patient who weighs 66 kg, just add 40 to 66 and it gives you the same amount of 106 mL/hr.
- Neonate weighs 12 kg. What is the hourly fluid requirement?
  - First 10 kg = 40 mL/hr
  - Next 2 kg = 4 mL/hr
    - = 44 mL/hr
  - Estimated (NPO) fluid deficit- Hourly maintenance x hours NPO
    - Example
      - Patient weighs 81 kg. What is the estimated deficit if the patient has been NPO for 8 hours?
        First 10 kg = 40 mL/hr
        Next 10 kg = 20 mL/hr
        Last 61 kg = 61 mL/hr
        = 121 mL/hr
        121 mL/hr x 8 hours NPO
        = 968 mL

Surgical (Evaporative) Loss

Trauma extent	mL/kg/hr
Superficial	1-2
Minimal	2-4
Moderate	4-6
Severe	6-8

Average Blood Volumes

Age	Blood volume (mL/kg)
Premature	90-105
Term	80-90
Infant	70-75
Male	70
Female	65
Obese	Lean body weight plus 20%

Maximum allowable blood loss (MABL)
- (Estimated blood volume x (Initial hematocrit – Lowest acceptable hematocrit)) / initial hematocrit
- Lowest acceptable hematocrit is variable. A generally accepted low hematocrit value for a patient without myocardial ischemia is 21%. With myocardial ischemia, the accepted low hematocrit value is 27-30%.
- Example
  - The male patient weighs 82 kg and his initial hematocrit is 36%. This patient has no history of heart problems.
  - 82 kg x 70 mL/kg
    - = 5740 mL blood volume
  - (5740 mL x (36 – 21)) / 36
  - 5740 x 15 / 36
    - 2391 mL blood loss is estimated before the hematocrit would fall to 21%
  - % concentration means grams / 100 mL
  - 1:1,000 means 1 gram / 1,000 mL
  - Be able to convert % concentration to mg/mL; just move decimal place one place to the right.
  - Convert 1:100,000, 1:250,000 to mcg/mL
    - Just divide the denominator by 1 million
  - Concentration = amount / volume
  - Amount = concentration x volume
  - SVR = ( (MAP – CVP) / CO ) X 80
  - Cardiac output
  - Bmi

REFERENCE: Nagelhout Nurse Anesthesia 7^th edition, pages 55-79.

I. BASIC SCIENCES