Chemical Reactions and Metabolism PDF

Chemical Reactions and Metabolism NSG 741: Genetics, Chemistry, and Physics of Anesthesia School of Nursing  Carbohydrate Metabolism and Formation of ATP Chapter 69 School of Nursing Metabolism The chemical processes that all...

Chemical Reactions and Metabolism NSG 741: Genetics, Chemistry, and Physics of Anesthesia School of Nursing  Carbohydrate Metabolism and Formation of ATP Chapter 69 School of Nursing Metabolism The chemical processes that allow cells to continue living. A most of the chemical reactions of the cell are concerned with taking chemical energy from foods and making it available for physiological processes. Two forms of metabolism are anabolism (synthesis) and catabolism (breakdown). School of Nursing Reactions Worth Knowing Dehydration synthesis (anabolic reaction) One monomer forms a covalent bond with another monomer , releasing H2O (Use energy). Hydrolysis (catabolic reaction) Polymers turn back to monomers when bond is lysed by addition of H2O (Release energy). School of Nursing Energy Foods Fats Carbohydrates Proteins These can be oxidized by the cell to release large amounts of energy. The phosphate bond is a high energy bond. Aerobic metabolism produces much more ATP than anaerobic. School of Nursing Coupled Reactions Chemical energy in foods must be released slowly. Energy is removed, then linked with reactions that drive cellular processes, like: Membrane pumps Protein synthesis Muscle contraction School of Nursing ATP – Adenosine Triphosphate ATP is an intermediate compound that has the ability to enter into many coupled reactions. Present throughout the cell. The amount of energy in each high-energy bond per mole of ATP is 12,000 calories in the body. School of Nursing Glucose (Dextrose) After absorption from the intestinal tract, much of fructose and almost all the galactose are rapidly converted to glucose in the liver. Glucose (C6H12O6) is the final common pathway for transport of carbohydrates into the cell. School of Nursing Transport of Glucose Through Cell Membrane Glucose cannot diffuse through membrane pores. Active co-transport or facilitated diffusion with a carrier protein is necessary. Insulin facilitates this process. School of Nursing Phosphorylation Immediately upon entry into the cell, glucose combines with a phosphate radical to form glucose-6- phosphate. Glucose can be used immediately for energy to the cell. This compound can be used immediately or stored in liver and muscles as glycogen, a polymer of glucose. School of Nursing Glycogenesis Formation of glycogen, a starch. School of Nursing Glycogenolysis Breakdown of glycogen to glucose in the liver. Makes glucose available. Each branch of the glycogen splits away by phosphorylation via phosphorylase. Hormones, epinephrine and glucagon can activate phosphorylase. School of Nursing Release of Energy from Glucose School of Nursing Glycolytic Pathway 1 gram-mole of glucose releases 686,000 calories of energy and only 12,000 calories is required to form 1 gram-mole of ATP. Many enzymes allow the glucose molecule to be oxidized a little at a time so that the maximum amount of energy is captured as ATP. Energy is released in packets yielding 38 moles of ATP per mole of glucose. School of Nursing Glycolysis The most important means of releasing energy from glucose is initiated by glycolysis (glucose lysing). 10 steps are involved. The end products of glycolysis are then oxidized to produce energy (ATP). Glycolysis occurs in the cytoplasm. Glucose (6 C) is split into 2 molecules of pyruvic acid (3 C). School of Nursing Glycolysis Net gain of ATP from one mole of glucose is 2 pyruvic acid molecules + 2 ATP molecules + 4 H. Efficiency of ATP formation is 43%. The 2 pyruvic acid molecules combine with Coenzyme A to form Acetyl-CoA which will yield up to 6 ATP molecules later. School of Nursing Citric Acid Cycle (Krebs Cycle) Reactions occur in matrix of mitochondria. The reaction begins when Acetyl CoA combines with oxaloacetic acid to form citric acid, the first product. The reaction begins and ends with the production of oxaloacetic acid. 24 hydrogen atoms are released for each molecule of glucose (4 during glycolysis, 4 forming acetyl-CoA, 16 Krebs cycle) 24 total so far. School of Nursing Citric Acid Cycle (Krebs Cycle) 20 of the hydrogen atoms combines with NAD+ via dehydrogenase. During the next several stages, water is added, and carbon dioxide and hydrogen atoms are released. 2 molecules of ATP are produced. School of Nursing Net Reaction per Molecule of Glucose in Citric Acid Cycle 2 Acetyl-CoA + 6 H2O + 2 ADP  4 CO2 + 16 H + 2 CoA + 2 ATP School of Nursing Oxidative Phosphorylation Oxygen is required. In the mitochondria, NADH is split into NAD+, H+, and e- by oxidation of hydrogen. The electrons enter the Electron Transport Chain. Energy released in these reactions is captured as a proton gradient, which is then used to make ATP. The process is called chemiosmosis. Electron Transport Chain + chemiosmosis = oxidative phosphorylation School of Nursing School of Nursing Summary of ATP Formation Glycolysis: 4 ATP made, 2 ATP used = 2 ATP Citric Acid Cycle: 2 ATP Electron Transport: 34 ATP TOTAL 38 ATP 456,000 cal stored as ATP and 686,000 cal available from glucose = 66% efficient. Feedback control mechanisms can initiate or stop ATP formation. School of Nursing Anaerobic Glycolysis This process is wasteful of the energy available in glucose. Pyruvic acid + NADH + H+ -> LACTIC ACID We measure this in the OR. It tells how well the cells are using oxygen. When oxygen is available again, lactic acid can be reconverted back to glucose or energy. School of Nursing Storage of Glucose Glycogen stores fill up first. The remaining excess is stored in fat. School of Nursing Gluconeogenesis When glucose is unavailable, it can be synthesized from fats (glycerol) and proteins (amino acids). Low blood glucose concentration is the trigger. Low blood glucose triggers the adenohypophysis to release corticotropin. This stimulates the adrenal cortex to release cortisol. Cortisol causes cells to break proteins into amino acids, which are ideal for the liver to convert to glucose. This is catabolic metabolism. School of Nursing Lipid Metabolism Chapter 69 School of Nursing Lipid Metabolism Lipids are the cellular fuels with the highest energy content. Lipids are the most efficient substances in which cells store energy. Lipids include triglycerides (neutral fat), phospholipids, cholesterol, and a few others. School of Nursing Fatty Acids Simple, long-chain hydrocarbon organic (carboxylic) acids. Contain –COOH (carboxylic group). Generalized formula: CH3(CH2)14COOH Palmitic acid: CH3(CH2)14COOH School of Nursing Triglycerides Three long-chain fatty acid molecules bound with one molecule glycerol. Glycerol is a triple alcohol: 3 –OHs School of Nursing Absorption of Fats Dietary triglycerides are broken to monoglycerides and fatty acids in the intestines. While passing through the intestinal epithelial cells, they are broken down and repackaged as new triglycerides called chylomicrons. Chylomicrons are absorbed into the lymphatic system. Plasma appears turbid 1 hour after a high-fat meal. School of Nursing Uptake Into Cells Lipoprotein lipase in capillary endothelium of fat and liver cells hydrolyzes triglycerides into fatty acids and glycerol. Fatty acids diffuse into cells. Once inside, fatty acids can resynthesize into triglycerides and are stored that way. School of Nursing Transport Through Body When lipids are needed, fat cells hydrolyze triglycerides to fatty acids and glycerol. These enter the blood and combine with albumin to become free fatty acids. School of Nursing Fat Deposits Adipose tissue is called fat deposits, or simple tissue fat. Fats are also stored in the liver. Can have NASH from this Fat cells of adipose tissue are 80-95% full of triglycerides. Lots of biproducts within fat, it is not benign, it is very responsive to factors. School of Nursing Use of Triglycerides for Energy Up to 50% of the calories in the typical American diet come from fats. Triglycerides hydrolyze to fatty acids and glycerol. Glycerol is changed to glycerol-3-phosphate and enters glycolytic pathway for glucose breakdown. Fatty acids enter mitochondria and are oxidized. School of Nursing Beta-Oxidation In several steps, fatty acids are converted to Acetyl-CoA, a process called beta-oxidation. Acetyl-CoA enters the citric acid cycle just as in carbohydrate metabolism. Tremendous amounts of ATP are formed from beta- oxidation of fatty acids. Complete oxidation of one molecule of stearic acid produces 148 molecules of ATP (2 ATP are used so net gain is 146 ATP). School of Nursing Ketosis When no carbs are available, fats are oxidized to fuel the body (Adkin’s diet). High concentrations of B-hydroxybutyric acid, acetoacetic acid, and acetone are metabolites. These substances are called ketone bodies. Causes: Starvation Diabetes mellitus High fat, low carb diet School of Nursing Regulation of Fat Utilization Epinephrine and norepinephrine activate triglyceride lipase, increasing FFA by as much as 8X. Rate of fatty acid use increases: Corticotropin release from anterior pituitary Glucocorticoid release from adrenal cortex Decreased secretion of insulin School of Nursing Phospholipids Contain a fatty acid molecule and a phosphoric acid radical. Also, a nitrogenous base. 3 types: Lecithins Cephalins Sphingomyelins School of Nursing Uses of Phospholipids Cell membranes – very important throughout the body. Constituents of lipoproteins. Thromboplastin – clotting. Sphingomyelin is a component of myelin sheaths surrounding nerve cells. Phospholipids act as phosphate radical donors. School of Nursing Uses of Cholesterol Forms cholic acid in liver, aiding digestion of fats (bile). Converted to adrenocortical hormones. Converted to estrogen, progesterone, and testosterone. Forms corneum of the skin, making us waterproof. School of Nursing Atherosclerosis A disease of the large arteries where fatty lesions (atheromatous plaques) are deposited. Similarly, arteriosclerosis causes thick, stiff vessels of all sizes. Lesions are primarily cholesterol. Connective tissue grows in the plaques, making vessel walls stiff (sclerotic). Plaque can occlude the vessel over time. Atherosclerotic vessels can easily rupture. School of Nursing Factors that Lead to Atherosclerosis Familial Physical inactivity and obesity Diabetes mellitus Hypertension Hyperlipidemia Smoking School of Nursing Prevention of Atherosclerosis Eat a low-fat diet - Most important! Don’t smoke Exercise Control blood pressure Control blood glucose Eat oat bran - binds bile acids in gut Statins inhibit HMG-CoA reductase, needed for synthesis of cholesterol School of Nursing Protein Metabolism Chapter 70 School of Nursing Protein Metabolism 3/4 of body solids are proteins. Proteins are made up of a variety of 20 amino acids. Chains are AA are held together by peptide linkages and then hydrogen bonding. Functions: Structure; Enzymes; Oxygen transport; Nucleoproteins; Muscle contraction; Cellular functions School of Nursing Regulatory Protein Regulatory Protein – Transmits a message from a chemical signal to another portion of the cell. G Protein Coupled Receptor – Regulatory protein that passes a message through the cell membrane. Cell communication. Ligand is the chemical substance binding to this receptor. The internal receptor binds to a G protein. Door-bell second messenger event. Downstream events are termed second-messenger events. These additional messages are received by other cells resulting in action in the second cell. Thus, cell communication. School of Nursing Transport of Amino Acids When proteins are digested in the gastrointestinal tract, they are converted to amino acids. Protein digestion and absorption take 2-3 hours. Amino acids enter cells by active transport or facilitated diffusion. Amino acids are lost in the urine if their concentrations exceed renal threshold for reabsorption. School of Nursing Storage of Amino Acids Almost immediately after entering cell, amino acids are incorporated into new proteins. When blood levels of an amino acid are low, these amino acids are transported out to restore the supply. A reversible balance of amino acids and various proteins exists. Cancer cells are prolific users of amino acids; therefore, the proteins of other cells can be depleted. School of Nursing Major Plasma Proteins Albumin – colloid osmotic pressure Globulins – enzymes, immune system Fibrinogen – coagulation School of Nursing Dietary Amino Acids 10 Essential AAs – cannot be synthesized; must be ingested 10 Nonessential AAs – can be synthesized, but are still needed for protein synthesis School of Nursing Use of Proteins for Energy Occurs in the liver. Begins with deamination – removal of an amino group (- NH2) from an amino acid. Aminotransferases are enzymes responsible for deamination. School of Nursing Urea Ammonia created through deamination of AAs is removed from blood through conversion to urea. Ammonia is a neurotoxin. Urea is synthesized in the liver. Excreted by the kidneys. School of Nursing Oxidation of Deaminated Amino Acids The resulting keto acid is degraded into a substance that can enter the citric acid cycle. This substance is oxidized like acetyl-CoA to produce ATP. Conversion of AAs into keto acids or fatty acids is called ketogenesis. School of Nursing Obligatory Degradation of Proteins 20-30 g of protein is degraded to AA and oxidized regardless of dietary intake. Eating less protein than this results in starvation. Carbohydrates are protein sparers. School of Nursing Hormonal Regulation of Protein Metabolism Growth hormone: increases transport of AA into cell, promoting protein synthesis. Insulin accelerates transport of AA into cells. Glucocorticoids: increase breakdown of extrahepatic proteins increasing available AAs. Testosterone: increases deposition of proteins in muscle tissues. Thyroxine: increases rate of metabolism, either catabolism or anabolism. School of Nursing School of Nursing  Aqueous Solutions & Concentrations; Solubility, Diffusion, and Osmosis NSG 741: Genetics, Chemistry, and Physics of Anesthesia School of Nursing Terminology Solute—the material that got dissolved; the component of the solution present in the smaller quantity. Solvent—material that does the dissolving. Solution—homogeneous mixture that consists of one or more solutes uniformly dispersed at the molecular or ionic level throughout a medium known as the solvent. Homogeneous mixture—not possible to discern phase boundaries between the components of the mixture. 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 gases. School of Nursing Mixtures of oxygen and nitrous oxide are also solutions. Solution Concentrations Molarity Molality Also called molar concentration Also known as molal Moles of solute per liter of concentration solution Expresses concentration in Common concentration unit in terms of moles of solute per chemistry kilogram of solvent Abbreviated with a capital M Can be used as a conversion Because molarity has units of factor between moles of solute and kilograms of moles per liter, molar solvent concentrations are conversion factors between moles of Abbreviated with a lowercase material and liters of solution m School of Nursing Solution Concentrations: Molality Because solutions in the laboratory are usually measured by volume, molarity is very convenient to employ for stoichiometric calculations. However, since molarity is defined on moles of solute per liter of solution, molarity depends on the temperature of the solution. Molar concentration will decrease as the 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. It is useful for physical chemistry. School of Nursing Solution Concentrations: Molality Much 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 to take this into account. 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. School of Nursing Solution Concentrations Percent Percent by Weight to Volume (%w/v) The percent of concentration you encounter in a clinical setting when measuring out a volume of medicine in a syringe. Defined as grams of solute per 100 ml of solution. There are two mathematically equivalent statements of this definition: The first formulation is useful as a conversion factor between grams of solute and milliliters of solution. School of Nursing Solution Concentrations Percent Percent by Weight (% w/w) – e.g., topical creams Exactly analogous to the definition of percent weight to volume, except the denominator expresses the quantity of solution in terms of grams, not milliliters. To relate percent by weight to percent weight to volume, we need to employ the density of the solution. Percent by Volume (% v/v) Never used in an analytical laboratory, because volumes are not additive. Because of strong intermolecular interactionsSchool of Nursing between ethanol Solution Concentrations Normality (acid-base) and Equivalents(talking about normality) An equivalent (abbreviated Eq) is analogous to a mole. Normality is analogous to molarity (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. School of Nursing  Solution Concentrations The concentration of extremely dilute solutions is often expressed as parts per million. A ppm concentration is analogous to a percent concentration, except you are comparing the amount of solute to a million grams of solution, rather than 100 grams. 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, control of nitrous oxide to 25 ppm during anesthesia should limit Schoolconcentrations of Nursing of the halogenated gases to less than 0.5 ppm. Solution Concentrations 100% N2O = 1,000,000 ppm 1% N2O = 10,000 ppm 0.01% N2O = 100 ppm 0.0025% N2O = 25 ppm School of Nursing 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.) School of Nursing Epinephrine How do you make up 25 ml of 2% lidocaine with 1:250,000 epinephrine? Take an ampule of 1:1000 epinephrine (i.e., 1 mg/ml). Add 10 ml of saline to give 1:10,000 (i.e., 100 micrograms per ml). Add 1 ml of this epinephrine solution to 24 ml of 2% plain lidocaine. (i.e., 100 micrograms per 25 ml = 4 micrograms per ml). How do you prepare a 1:200,000 solution of epinephrine in 20 ml of 1% lidocaine? Take 0.1 ml of epinephrine from a 1:1000 ampule 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% School of Nursing lidocaine with 1:200,000 epinephrine. How much of each drug 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). More water is needed, so it is not a covalent bond.School of Nursing Solubility 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. School of Nursing Solubility Solubility is enhanced by intermolecular interactions between substances that have similar electron configurations. “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. The similar polarity of water and salt's constituent parts promote dissolving. Substances like nitrogen, carbon dioxide, and oxygen are nonpolar. They are typically insoluble in a polar compound like water. School of Nursing  Effect of Temperature on Solubility The solubility of solid and liquid solutes in liquid solvents 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. Greater kinetic energy 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 the slower emergence of hypothermic patients receiving volatile agent general anesthetics. The hypothermic patient retains anesthetic gases in the blood because of increased solubility related to temperature. School of Nursing Energy Changes & the Solution Process 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. Enthalpy H is equal to the heat Q as long as the pressure remains constant. School of Nursing Energy Changes & the Solution Process 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. School of Nursing If the energy released by solvation is greater than the Energy Changes & the Solution Process Energy is absorbed to break bonds which is an endothermic process (cooling effect). Energy is released when new bonds form which is an exothermic process (warming effect). 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. For example, if the temperature increases with an endothermic reaction, it is essentially like adding more reactants to the system. Then, if the temperature increases with an exothermic reaction, it is essentially like adding more products to the system. School of Nursing Energy Changes & the Solution Process Solubility of a solute decreases with increasing temperature if ΔHsoln is negative (exothermic). Solubility of a solute increases with increasing temperature if ΔHsoln is positive (endothermic). According to Le Châtelier’s Principle, the system will attempt to restore/maintain equilibrium. More reactants (endothermic) which would favor a shift in the equilibrium to the right (products). More products (exothermic) will shift the equilibrium to the left (reactants). School of Nursing Factors Affecting Solubility Effect of Pressure on Solubility As pressure increases, the solubility of a gaseous solute in a liquid solvent increases. Since solids and liquids are not very compressible, at least not compared to gases, 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 where S = solubility, kH = Henry’s law constant, and Pgas = partial pressure of the gas School of Nursing  Henry’s Law The main applications of Henry’s law 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. School of Nursing Henry’s Law 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, how much O2 is dissolved in arterial blood when the PaO2 is 300 mmHg? 0.9 ml O2 /100 ml blood dissolved How much does dissolved O2 in the blood increase when the PaO2 increases from 100 to 500 mmHg? 0.3 versus 1.5 ml O2 /100 ml blood dissolved or a difference of 1.2 School of Nursing Henry’s Law 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 How about CO2? The amount of CO2 that dissolves in blood is 0.067 ml/100 ml blood/mmHg. How much CO2 is dissolved in arterial blood when PaCO2 is 50 mmHg? 50 x 0.067 = 3.35 ml CO2/100 ml blood. School of Nursing 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 vapor pressure of a volatile component of a solution (P) is equal to the vapor pressure of the pure substance (Po) times the mole fraction (χ) of that substance. School of Nursing Henry’s Law vs. Raoult’s Law Overall, the difference is that Henry's law takes care of what happen IN the solution when you have gas over it. 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 (e.g., water). School of Nursing Colligative Properties of Solutions Boiling Point 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. School of Nursing Colligative Properties of Solutions Freezing Point 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. School of Nursing NACL Example The more salt (or any solute) added to water, the more you raise the boiling point. Freezing point is another colligative property that works the same way: If you add salt to water, you lower its freezing point as well as raise its boiling point. School of Nursing Colligative Properties of Solutions Diffusion is the net movement of one type of molecule through space as a result of random motion to minimize a concentration gradient. Temperature is directly proportional to kinetic energy. 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. Greater velocity correlates with faster diffusion. Thus, molecules with smaller mass will diffuse faster. KE = (½)mv2 School of Nursing Colligative Properties of Solutions 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. The formula for this relationship is as follows: 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. 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. School of Nursing Colligative Properties of Solutions Permeable/Semipermeable Membrane: Diffusion may occur through open space or through permeable membranes (tissues). Diffusion of a fluid (gas or liquid) through a permeable membrane is dependent on five factors: Concentration gradient, tissue area, and fluid tissue solubility are directly proportional to diffusion. Whereas membrane thickness and molecular weight are inversely proportional to diffusion. School of Nursing Colligative Properties of Solutions 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. School of Nursing Colligative Properties of Solutions 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. Normal oncotic pressure is approximately 28 mmHg. The vascular system is a semipermeable membrane that responds to intravascular delivery of colloids by sequestering fluid. School of Nursing Colligative Properties of Solutions Osmotic Pressure: Osmotic pressure (symbolized as capital pi, Π) 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. Most capillary walls are permeable to small solutes and do not exert an osmotic effect. Albumin (MW is 69,000) does not penetrate the capillary wall and does provide osmotic pressure. Albumin is the major determinant of intravascular volume. School of Nursing School of Nursing School of Nursing Diffusion and Anesthesia Diffusion is a passive process driven by entropy. A gas or liquid will become uniform over time. The diffusion rate varies depending on the medium (what tissue it's going through). The diffusion of oxygen and nitrous oxide represents both positive and negative consequences of this process. 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. Distention of the bowel during nitrous oxide delivery has also been documented. School of Nursing Diffusion and Anesthesia Apneic oxygenation is well known and exemplifies the beneficial process of diffusion. The diffusion of gases across biological tissues is expressed by Fick’s Law: 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 equation allows determination of pulmonary gas exchange. The diffusion hypoxia that occurs after the delivery ofNursing School of nitrous oxide is discontinued, and low inspired oxygen is Fick’s Law of Diffusion Diffusion Rate (J) = (P1-P2) x (Area) x (Solubility) (Membrane thickness) x (√MW) Fick’s law of diffusion for gas explains: Diffusion hypoxia COPD patient and slow gas induction Cardiac output calculation N2O leads to increased volume (or pressure) in gas spaces of the body Graham’s law explains why smaller substances diffuse in greater quantities. Second gas effect (interrelated with concentration effect) High fresh gas flow turbulence (density) School of Nursing Need to Know Even though CO2 is larger than O2, CO2 diffuses 22 times faster across the alveolar and capillary membranes than O2 because it is much more soluble in fluid than O2. Equilibration of an inhalational agent or any gas occurs in the body when the partial pressure of the gas is the same everywhere. 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. School of Nursing Need to Know Non-gases? Our drugs. Liquids we would give The 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) Large (high molecular weights) Why do ions like Na NOT penetrate lipid bilayers? Ionized particles are hydrophilic and lipophobic! School of Nursing Colloids Colloids are similar to solutions in that they consist of one phase uniformly dispersed in a second phase. Examples: milk, blood, paint, and jelly. Not true solutions because the particles in the dispersed phase are not the size of molecules or ions. Particles in a colloid range in size from 10 nm to 200 nm Colloidal particles cannot be filtered and do not settle out of solution. Colloids can be stable for years if they are stored under controlled conditions. Colloids exhibit the Tyndall effect, whereas solutions do not. Particles of a colloid are large enough to scatter light School of Nursing passing through. School of Nursing  Acids, Bases, and Salts NSG 741: Genetics, Chemistry, and Physics of Anesthesia School of Nursing Who cares? Overview Many biological and drug molecules have acidic and or basic properties. In the patient, acidic and basic properties of a drug are important for two reasons. Water solubility (lipophilic-alkanes, benzene; hydrophilic- alcohols, amines) Binding to the site of action An acid is a molecule that donates a proton. A base is a molecule that accepts a proton. An acid that has donated a proton is a conjugate base. A base that has accepted a proton is a conjugateSchool acid. of Nursing Who cares? Overview An acid can accept a pair of electrons. A base can donate a pair of electrons. pH is a value between 0 and 14. A strong acid fully dissociates into H+ and its conjugate base. A weak acid does not fully dissociate. The pKa puts a number to a molecule's acidity or basicity – how weak of an acid or base. Knowing the pH and pKa allows you know if the drug will be more ionized or unionized. School of Nursing Chemical Equilibria Le Châtelier’s (le-SHOT-lee-ay) Principle States that equilibrium is a good thing, and nature strives to attain and/or maintain a state of equilibrium. Changing Concentration If you add products, the equilibrium will shift toward reactants. If you remove products, the equilibrium will shift toward products. Changing Temperature Increasing temperature favors endothermic processes. Changing Volume and Pressure Significantly impacts equilibrium reactions only when at least one of the reactants or products is a gas. Decreasing volume increases pressure. School of Nursing Chemical Equilibria The Equilibrium Constant A system is in a state of equilibrium when there is a balance between reactants and products. This balance is defined by thermodynamic parameters, namely bond strengths and the intermolecular forces between all the molecules in the system. The equilibrium constant (K) is the numerical description of that balance. School of Nursing  Chemical Equilibria As K increases, the reaction tends to increasingly favor products and the forward reaction becomes more favorable. As K decreases, the reaction tends to increasingly favor starting materials, and the reverse reaction becomes more favorable. Solids and Liquids Pure solids or liquids comprise a different phase from where reactions in aqueous media occur. The concentration of solids, liquids, and water (as a solvent) do not appear explicitly in the equilibrium constant expression. Reversing a Reaction When you reverse the equation for a chemical reaction, Kforward is the reciprocal of Kreverse. Products to reactants or materials. School of Nursing Acids and Bases Definition of Acids and Bases Arrhenius definition (most operational definition) Acid–species that increases the hydronium ion (H3O+) concentration in an aqueous solution. Base–species that increases the hydroxide ion (OH–) concentration in an aqueous solution. Brønsted definition (most generally useful definition) Acid–species that donates a hydrogen ion (H+) to a base. Base–species that accepts a hydrogen ion (H+) from an acid. School of Nursing Acids and Bases Conjugate Acid-Base Pairs The charge on the conjugate acid is always one greater than the charge on its conjugate base. When an acid gives away its hydrogen ion to a base, the acid is converted into its conjugate base. When a base accepts a proton from an acid, the base is converted into its conjugate acid. In generic form, we can express this process as: HA + B → A− + BH+ Amphiprotic Species Can behave as either an acid or a base. School of Nursing Acids and Bases Strong Acids Very determined to foist their proton off onto a base. Essentially 100% ionized when dissolved in water, but this is not an equilibrating process, so all of the starting materials are converted into products. Strong acids are relatively rare. Strong Bases In water, the strongest possible base is the hydroxide ion, OH−. A strong base ionizes essentially 100% to produce the OH − ion, so a strong base is a soluble ionic hydroxide. School of Nursing Acids and Bases Weak Acids Are able to donate hydrogen ions to bases but are less determined to do so than strong acids. When a weak acid dissolves in water, it establishes a dynamic equilibrium between the molecular form of the acid and the ionized form. Weak Bases Can accept hydrogen ions from acids but are less determined to do so than strong bases. Do not completely ionize in water to produce an equivalent concentration of the hydroxide ion, because when a weak base dissolves in water, it establishes a dynamic equilibrium between the molecular form and the ionized form. School of Nursing Acids and Bases Polyprotic Acids A diprotic acid has two hydrogen ions to donate, so a diprotic acid can behave as an acid twice. A triprotic acid has three hydrogen ions to donate. Being able to act as acid twice or three times. The number of acidic protons is not necessarily the number of hydrogens in the molecular formula. The acidic hydrogen is bonded to a highly electronegative oxygen atom. The O—H bond is polarized toward the oxygen to a point that a base can snatch away the hydrogen as an H+ ion from the acetic acid molecule. School of Nursing The other three hydrogens are bonded to a carbon atom, and Acids and Base Strength Acid/Base Strength of Conjugate Acid–Base Pairs The stronger the acid, the weaker its conjugate base. The stronger the base, the weaker its conjugate acid. General guidelines The conjugate base of a really strong acid has no base strength. The conjugate base of a weak acid has base strength. The conjugate acid of a weak base has acid strength. School of Nursing Acid–Base Reactions Involve a transfer of a hydrogen ion from the acid to the base In order to predict the products of an acid–base reaction: Identify which is the acid and which is the base. Move an H+ ion from the acid to the base, converting the acid into its conjugate base and the base into its conjugate acid. Any acid–base reaction has two acids and two bases: One acid and one base on the reactant side. Conjugate acid and conjugate base on the product side. The base almost always has a lower (more negative) charge than the acid. School of Nursing The reaction equilibrium always favors the formation of the Measuring Acidity: The pH Function The p in pH is a mathematical operator that means the negative logarithm of, and the H in pH means hydrogen ion concentration, so the definition of pH is pH = −log[H+]. A logarithm function is a way to map a vast range of values onto a much smaller set of values. pH values have no intrinsic units—logarithms represent “pure numbers”. Each change of 1 pH unit means the hydrogen ion concentration is changing by a factor of 10, so small changes in pH correspond to much larger changes in acidity level. School of Nursing Measuring Acidity: The pH Function Water has some very weak acid–base properties, and therefore sets some limits on the parameters of the pH scale. A tiny fraction of water molecules dissociates or ionizes into a hydrogen ion and a hydroxide ion: H2O ⇄ H+ + OH−. In pure water, the concentrations of the H+ and OH− ions are equal: [H+] = [OH−] in pure water The pH of pure water is 7.00. School of Nursing Measuring Acidity: The pH Function Relationship Between pH and pOH Because pH and pOH are derived from the ionization of water, there is a fixed relationship between them. The pH plus the pOH of any aqueous solution (at 25°C) always adds up to 14.00: 14.00 = pH + pOH pKa and pKb The equilibriums constants for acids and bases are commonly presented as p-functions. The pKa and pKb of a conjugate acid–base pair sum to give School of Nursing 14.00: Other Acidic Species Nonmetal oxides dissolve in water to give acid solutions. The most physiologically important example is carbon dioxide. Buildup of carbon dioxide in the blood results in acidosis. In cellular tissue, where the carbon dioxide concentration is relatively high, the increased acidity slightly alters the structure of hemoglobin and facilitates the release of oxygen. School of Nursing Other Acidic Species Carbon dioxide is a nonmetal oxide because it is a compound composed of a nonmetal and oxygen. Nonmetal oxides are sometimes called acid anhydrides because they are produced by stripping water from an acid. When carbon dioxide dissolves in water, it combines with a water molecule to give carbonic acid: CO2 + H2O ⇄ H2CO3. When the carbonic acid forms, it dissociates according to its acid strength: H2CO3 ⇄ H+ HCO−3. So, when CO2 dissolves in water, the pH drops. School of Nursing Buffers A pH buffer is a solution that resists changes in pH. It contains a weak acid (HA) and its conjugate base (A−) or a weak base and its conjugate acid. If a strong base is added to a buffered solution, the weak acid in the buffer HA reacts with the hydroxide ion to give water and the weak base A−. HA + OH− ⇄ H2O + A− This results in converting a strong base OH− into a weak base A−. If a strong acid is added to a buffered solution, the weak base in the buffer (A− ) reacts with the H+ ion to give HA. School of Nursing A− + H+ ⇄ HA Henderson–Hasselbalch Equation (Estimates pH of the buffer system) This equation predicts that when a basic drug is placed into a relatively more acidic environment, the conjugate acid will predominate. If the molecule is a weak base and pH is > the pKa of the drug, then the unionized fraction predominates. If the molecule is a weak acid and the pH is < the pKa of the drug, then the unionized fraction predominates. If the molecule is a weak base and pH is < the pKa of the drug, then the ionized fraction predominates. If the molecule is a weak acid and the pH is > the pKa of the drug, then the ionized fraction predominates. As pKa get further away from physiologic pH, the degree of ionization increases. The closer the pKa is to the pH of the blood, the faster the onset. School of Nursing Henderson–Hasselbalch Equation School of Nursing School of Nursing Acid-Base Balance & Respiratory System The respiratory system plays an important role in maintaining normal pH balance within the body. It works along with the kidneys and the buffer systems to balance the acids and bases of the blood and other body tissues, allowing them to function normally. Hydrogen ions interact with negatively charged regions of other molecules, such as proteins, altering their structural conformation and in doing so altering their behavior. Blood pH alters the activity of various enzymes, thereby changing metabolic functions in all body tissues. School of Nursing Acid-Base Balance &Respiratory System In addition to the efforts of the respiratory system and kidneys to regulate pH levels, buffers in the human body maintain pH within the physiologic range. The buffers consist mainly of bicarbonate, phosphate, and proteins. From values for PaCO2 and HCO3 are used to determine if the disturbance is respiratory or metabolic. The respiratory system can rapidly compensate for metabolic acidosis or alkalosis by altering alveolar ventilation. The total body bicarbonate deficit is equal to the base deficit (in mEq/ L) that is obtained from the blood gas values. Complete correction of the base deficit is not indicated; only half of the calculated dose of bicarbonate is initially recommended. School of Nursing Human Buffer Systems Blood System: Normal: Bicarbonate buffer is the most important. pH – 7.35-7.45 Hemoglobin is the second PaCO2 – 35-45 most important. HCO3 – 22-26 Respiratory System: Altering ventilation to change PaCO2 is the key. Renal System: Reabsorption of filtered bicarbonate. Removal of titratable acids. Formation of ammonia. School of Nursing Anion Gap – Metabolic acidosis Anion gap helps determine the cause of the metabolic acidosis. Anion gap = Major cations – Major Anions or NA – Cl + HCO3 The value is usually 8-12 mEq/L. Accumulation of acid? > 12? Gap acidosis. Loss of bicarbonate or ECF dilution? Non-gap acidosis. School of Nursing Interpretation of Arterial Blood Gases Analysis of ABGs can provide useful information concerning the relationship of acid production and acid removal by the lungs and kidneys. Acid-base disturbances can be categorized into four major groups: respiratory acidosis, metabolic acidosis, respiratory alkalosis, and metabolic alkalosis. Each can be considered compensated under certain conditions. In spite of observing a compensatory change in CO2 or bicarbonate, an acid-base disorder is considered uncompensated if that mechanism has not been able to bring the pH back into a normal range. School of Nursing Acidosis Any process that leads to an elevation in PaCO2 tends to lower arterial pH, resulting in respiratory acidosis. An acute change in PaCO2 of 10 mm Hg is associated with a change in pH of 0.08 units. An increase in PaCO2 with a normal bicarbonate level is termed uncompensated respiratory acidosis. Metabolic acidosis should more properly be referred to as nonrespiratory acidosis because it does not always involve alterations in metabolism. Causes of this condition include ingestion (poisoning), infusion, production of a fixed acid (lactic acidosis), and decreased excretion of acid by the kidneys. A base change of 10 mEq/L is associated with a pH change of 0.15 unit. School of Nursing Alkalosis As the pH rises, this hyperventilation results in respiratory alkalosis. Metabolic alkalosis occurs when fixed acid loss is increased or when the intake of bases is abnormally high. School of Nursing School of Nursing Treatment of Blood Gas Abnormalities For the patient who is mechanically ventilated, respiratory acidosis and respiratory alkalosis can be treated with a simple increase or decrease in the amount of alveolar ventilation. To restore stable and spontaneous circulation, mild to moderate metabolic acidosis can be treated with hyperventilation and correction of shock. School of Nursing School of Nursing