NUR 751 Exam 3 2024 Study Guide Summer.docx

Study Guide for NUR 751 Exam 3 2024 *Disclaimer: Be aware this outline is not exhaustive. To be successful on Exam 3 you must have read and processed the following textbook chapters as well as reviewed the PowerPoint presentations. You all are literally going to be passing gas for a living, you sho...

Study Guide for NUR 751 Exam 3 2024 *Disclaimer: Be aware this outline is not exhaustive. To be successful on Exam 3 you must have read and processed the following textbook chapters as well as reviewed the PowerPoint presentations. You all are literally going to be passing gas for a living, you should know this stuff inside and out.* 1. Stoelting: Chapter 4 Inhaled Anesthetics 2. Stoelting: Chapter 25 Respiratory Pharmacology 3. Guyton and Hall: Chapter 40 Principles of Gas Exchange I. Principles of Gas Exchange a. Be able to discuss the factors which influence to movement of gases across physiologic membranes to include: b. Ventilation and respiration are driven by gradients i. During ventilation, the negative pressure sucks air in (i.e. pressure gradient) and diffusion drives respiration (i.e. concentration gradient) ii. Partial pressure -- partial pressure of gas is proportional to the concentration of the molecules 1. Partial pressure of a gas is a reflection of its concentration and solubility coefficient i.e. Henry's Law a. Partial pressure = concentration/solubility coefficient 2. Henry's Law states that the partial pressure of an anesthetic in blood is proportional to the partial pressure of the anesthetic in alveoli 3. Dalton's Law of partial pressures P1+P2+P3 = Ptotal iii. Energy for diffusion is molecular kinetic energy iv. Net rate of diffusion is driven by pressure gradients, solubility, distance through which the gas must diffuse, cross-sectional area of the diffusion pathway, molecular weight of gas, temperature (temperature is relatively constant in human body), and diffusion coefficient 4. Diffusion coefficient is determined by the solubility and molecular weight of the substance (Graham's Law) b. Diffusion coefficient = relative rates at which different gases at the same partial pressure levels will diffuse c. O2 diffusion coefficient 1 d. CO2 diffusion coefficient is 20 e. CO2 is 20x more soluble than O2 v. Solubility -- the greater the solubility of gas, the greater the number of molecules available to diffuse for any pressure gradient 5. Gas/solubility coefficient is the likelihood of a gas being dissolved in blood 6. Solubility coefficient = measure of gas solubility in water f. When molecules are attracted in water, more of them can be dissolved without building up partial pressure g. When molecules are repelled by water, higher partial pressures will develop with fewer dissolved particles vi. Molecular weight vii. Temperature viii. Gases of respiratory importance (e.g. O2, CO2, N, etc) are all highly soluble in lipids and therefore highly soluble in cell membranes 7. Limiting factor in the diffusion of gases in tissues is the rate in which the gas diffuses through water c. Describe the changes in the partial pressures of atmospheric gases as they move from air to the alveolus. ix. Net diffusion is determined by difference between partial pressures x. In O2, partial pressure is greater in the gas phase in the alveoli so it will diffuse to lower pressure areas in blood xi. In CO2, partial pressure is greater in its dissolved state in blood, so it will diffuse to lower pressure in alveoli xii. Air (i.e. N+O+CO2) is almost totally humidified before reaching the alveoli xiii. Water vapor dilutes all the gases in air, which drives the partial pressures of the gases (N+O+CO2) down d. Discuss the importance of Functional Residual Capacity for maintaining a reservoir for gas exchange and limiting sudden changes in gas concentrations in the plasma. xiv. FRC is about 2300 mL, but only 350 mL of alveolar air is exchanged per breath xv. Multiple breaths are required to exchange most alveolar air xvi. Slow replacement of alveolar air is crucial to preventing sudden changes to gas concentrations in blood (e.g. you won't desaturate immediately when apneic due to FRC) e. Define: xvii. Dead space 8. Dead space air is air that does not participate in gas exchange/come in contact with the alveoli and is found in the respiratory passageways (e.g. pharynx, larynx, trachea) 9. Dead space air = anatomic dead space air + alveolar dead space air 10. Alveolar dead space air = air in alveoli that are ventilated but not perfused xviii. Expired air = dead space air + alveolar air xix. Respiratory unit = respiratory bronchiole, alveolar duct, atria, and alveolus xx. Pulmonary blood flow is described as a sheet of flowing water f. Predict the concentration of oxygen and carbon dioxide in an alveolus which: xxi. The concentrations and partial pressures of both O2 and CO2 in the alveoli are determined by the rates of absorption or excretion of the two gases and by the amount of alveolar ventilation. xxii. V/Q = ventilation perfusion ratio xxiii. Is ventilated but not perfused. i.e. V/0 11. When alveoli are ventilated but not perfused, the V/Q = infinity 12. Alveolar air equilibrates with the inspired air xxiv. Perfused but not ventilated. i.e. 0/Q 13. When alveoli are perfused but not ventilated, the V/Q = 0 14. Alveolar gas equilibrates with pulmonary capillary air to resemble the same pressures as mixed venous blood returning to the lungs 15. PO2 = 40; PCO2 = 45 xxv. Ventilated and perfused. 16. Matching of ventilation and perfusion 17. PO2 = 104; PCO2 = 40 xxvi. Shunt when V/Q is below normal 18. Shunt is blood passing through the pulmonary vasculature and not oxygenated resulting in underventilated alveoli 19. Perfusion \> ventilation h. Normal perfusion but inadequate ventilation 20. Total amount of shunted blood = physiologic shunt 21. There is a normal anatomic shunt in healthy individuals 22. The greater the physiological shunt, the greater the amount of blood that fails to be oxygenated as it passes through the lungs xxvii. Dead space when V/Q is greater than normal 23. Dead space occurs when alveolar ventilation is wasted because the work of ventilation never makes it to the blood 24. Ventilation \> perfusion i. Normal ventilation but inadequate perfusion j. Physiologic dead space = alveolar dead space + anatomic dead space xxviii. Smoking can lead to obstruction causing shunt and dead space ventilation g. Define diffusing capacity and the role of carbon monoxide is estimating diffusing capacity. xxix. Diffusion capacity = volume of gas that will diffuse through the membrane per minute per 1 mmHg partial pressure difference xxx. Diffusion capacity will be increased during exercise due to recruitment of capillaries, improved V/Q, and increased alveolar ventilation xxxi. Diffusion capacity for CO is used to estimate diffusion capacity for O2 25. Plasma concentration for CO is basically zero 26. Have patient inhale a known amount of CO and measure the amount of CO exhaled 27. Pressure difference across the respiratory membrane is equal to its partial pressure in measurement 28. DLCO in healthy men = 17 mL/min/mmHg h. Discuss the factors affecting the rate of diffusion of gases across the respiratory membranes. xxxii. Factors that determine rate of diffusion through the respiratory membrane = thickness of membrane, surface areas of membrane, diffusion coefficient, and the partial pressure difference xxxiii. Respiratory membranes will be thicker in edema and fibrosis -- harder for gases to diffuse across thicker membranes xxxiv. Surface area of membrane will be decreased in emphysema 29. Less surface area for gas exchange 30. 1/3 to ¼ decrease in surface area is a serious impediment to gas exchange II. Respiratory Pharmacology i. Autonomic NS and Non-adrenergic non-cholinergic (NANC) system influences bronchomotor tone j. Discuss the role and mechanism of action of inhaled beta~2~ agonists, anticholinergics agents, and corticosteroids in the management of asthma and chronic obstructive pulmonary disease \[COPD\]. xxxv. Inhaled B2 agonists 31. B2 agonists work by binding to the B2 receptor of pulmonary smooth muscle where stimulatory G proteins turn ATP into cAMP. The overall effect of this is smooth muscle relaxation/bronchodilation 32. Short acting b2 agonists used for rapid relief of wheezing, bronchospasm, and airway obstruction k. Albuterol, levabuterol, metaproterenol, pirbuterol l. Used for rapid relief of wheezing, bronchospasm, and airway obstruction 33. Long acting b2 agonists used for maintenance therapy m. Salmeterol, formoterol, aformoterol n. Used for maintenance therapy 34. Side effects of B2 agonists = tremors, tachycardia o. Temporary increased perfusion of poorly ventilated areas can lead to transient decreases in PaO2 p. Tolerance can develop due to downregulation and desensitization xxxvi. Systemic adrenergic agents are for rescue only xxxvii. Anticholinergic agents 35. Anticholinergic agents are not used for asthma maintenance 36. PNS is primarily responsible for bronchomotor tone 37. Anticholinergic act on M1 and M3 receptors in airway to reduce tone q. Anticholinergics inhibit binding of Ach to muscarinic receptors this causing reduced smooth muscle tone by decreasing release of calcium from intracellular stores 38. M1 and M3 receptors when bound by Ach produce bronchoconstriction and mucus production r. Ach binds to GPGR (M1 and M3) and causes smooth muscle contraction via increase in cGMP or G-protein activation 39. Ipatropium is short acting and used for maintenance in COPD. Ipatropium used for rescue therapy in COPD and asthma exacerbations 40. Tiotropium is long acting and used for COPD maintenance therapy xxxviii. Corticosteroids 41. In asthma, inhaled corticosteroids can be used as a monotherapy but is commonly used as a multimodal therapy 42. In COPD, inhaled corticosteroids are used in combination with long-acting beta2 agonists to synergistically reduce inflammation in SEVERE to VERY SEVERE COPD only 43. Mechanism of action = corticosteroid binds to glucocorticoid receptor and reducing expression of inflammatory gene products k. Discuss the mechanism of action of: xxxix. Leukotriene modifiers 44. Leukotrienes promote inflammatory responses in the lung and are responsible for bronchoconstriction and increased permeability in inflammation 45. Leukotriene modifiers are used in long term asthma therapy 46. Used in combination with short acting B agonists and or inhaled corticosteroids as an adjunct for asthma but not a first line therapy 47. Inhibitors decrease the production of leukotrienes 48. Antagonists block the receptor after leukotrienes are produced xl. Mast cell stabilizers 49. Reduce the granulation and release of the substances from mast cells (e.g. histamine) that are products of inflammation 50. Used for asthma 51. Not for emergency treatment or acute exacerbations xli. Methylxanthines 52. Very narrow therapeutic index -- not a first line treatment for asthma or COPD 53. Non-selective phosphodiesterase inhibitor s. Increases cAMP and cGMP t. Produces smooth muscle relaxation through inhibition of phosphodiesterase u. Inhibits mast cell release of histamine and leukotrienes 54. Side effects = diuresis, seizures, dysrhythmias, death 55. Require close monitoring e.g. blood level monitoring l. Compare and contrast the common features of COPD and asthma the differences in their management. xlii. COPD and asthma share inflammation as a common feature of their pathogenesis xliii. Asthma has mast cells xliv. COPD has neutrophils m. Describe the influence of the following classes of drugs on pulmonary artery pressure: xlv. NMDA receptor antagonists 56. E.g. ketamine 57. Stimulates the release and inhibits the neuronal uptake of catecholamines causing cardiostimulatory and bronchodilutory effects 58. Some studies note an increase in PVR (pulmonary vascular resistance) but it's a mixed picture due to its ability preserve cardiac stability xlvi. Ketamine, propofol, and midazolam all reduce bronchomotor tone xlvii. Volatile inhalation agents and N~2~O 59. Little to no effect on pulmonary vascular resistance (blood vessels) as compared to bronchorelaxation (smooth muscles) 60. Decreases in PAP likely reflect decreases in CO 61. N2O can cause pulmonary artery vasoconstriction due to catecholamine release -- typically avoided in PHTN 62. Deleterious effects of N2O can be offset with fentanyl at 50 mcg/kg (not a great idea....) xlviii. Neuromuscular blocking agents 63. **Rocuronium, cis-atracurium, and vecuronium** (intermediate acting NMBers) are noted for their cardiac stability and are unlikely to cause histamine release 64. **Cis-atracurium** is least likely to cause histamine release. **Atracurium** causes histamine release 65. **Pancuronium** can increase HR -- antagonistic/vagolytic effect on muscarinic receptors xlix. Vasopressors and inotropes 66. Sympathetic activation increases PVR l. Nitric oxide (NO) 67. Inhaled nitric oxide is preferentially delivered to ventilated lung units, decreasing intrapulmonary shunt 68. Approved for infants with ARDS 69. Can cause methemoglobinemia -- levels and nitrogen dioxide levels need to be monitored li. Phosphodiesterase inhibitors 70. Decrease metabolism and breakdown of cAMP and cGMP to cause vasodilation 71. Enhance the effects of NO III. Volatile Inhalation Agents and N~2~O n. Be familiar with the characteristics of the individual agents described in Ch. 4 in Stoelting's Pharmacology text. lii. Relative potency (MAC) = lower the MAC, the higher the potency liii. Immobility is how potency is measured 72. Immobility is mediated at spinal cord by depressing AMPA and NMDA currents 73. MAC amnesia is lower than MAC unconsciousness which is lower than MAC immobility liv. Blood gas coefficient = lower the BGC, the faster the onset and emergence lv. Determinants of alveolar partial pressures 74. The PA (arterial pressure) and ultimately the Pbr (partial pressure in brain) of an inhaled anesthetic are determined by input (delivery) into the alveoli minus uptake (loss) of the drug from the alveoli into the pulmonary arterial blood. Input of the inhaled anesthetic depends on the PI, alveolar ventilation, and characteristics of the anesthetic breathing system. Uptake of the inhaled anesthetic depends on the solubility, cardiac output (CO), and alveolar-to-venous partial pressure difference (PA − Pv). These six factors act simultaneously to determine the PA. lvi. Second gas effect = the ability of high-volume uptake of one gas (i.e. first gas) to increase the concentration of other gases (second gas) in the alveoli which ultimately speeds up the uptake of the second gas 75. When nitrous oxide is used as a carrier gas, it can speed up the onset of inhalational anesthetic agents lvii. How do inhalation agents work? 76. The mechanism is not fully understood, but may influence K+ channels, protein binding, dissolvability in lipids (Meyer-Overton hypothesis), potentiate inhibitory glycine receptors, decrease neurotransmission at glutamate receptors, block the effects of NMDA receptors lviii.  By controlling the inspired partial pressure (PI) (same as the concentration \[%\] when referring to the gas phase) of an inhaled anesthetic, a gradient is created such that the anesthetic is delivered from the anesthetic machine to its site of action, the brain. The primary objective of inhaled anesthesia is to achieve a constant and optimal brain partial pressure (Pbr) of the anesthetic. o. Diffusion hypoxia in nitrous oxide administration lix. Occurs when nitrous oxide is discontinued abruptly, leading to a reversal of partial pressure gradients such that nitrous oxide leaves the blood to enter the alveoli lx. Nitrous oxide dilutes the existing O2 in alveoli p. Be able to describe or discuss agents: lxi. Absorption/Solubility = from vaporizer to alveoli to pulmonary capillary lxii. Distribution = from capillary to site of action lxiii. Metabolism = liver or renal 77. Metabolism of agents reflect the chemical structure, hepatic enzyme activity, genetic factors, and blood concentration of the agent 78. Halothane metabolized in liver the most (15-20%) followed by sevoflurane, enflurane, isoflurane, and desflurane lxiv. Elimination/Recovery 79. Inhalation agents are primarily removed through lungs 80. Reversal of movement from absorption so agent will move from blood to alveoli to airway passages for exhalation 81. Washout of inhaled anesthetics from brain should be rapid because inhaled anesthetics are not highly soluble in brain 82. Continued uptake/removal in other tissues will depend on solubility and duration of exposure lxv. Goal of inhaled anesthetics is to establish alveolar partial pressure in the brain. The blood is the intermediary between the two lxvi. Factors influence the rate of anesthetic induction with inhalation agents: 83. Age -- decreases in lead body mass, increases in fat, and decreased cardiac output can make anesthetics more potent at smaller volumes v. Low cardiac output can lead to abrupt increases in alveolar pressure 84. Co-existing disease 85. Co-administration of other pharmacologic agents - lxvii. Factors influencing MAC 86. MAC is inversely affected by age 87. Decreased during pregnancy and returns to baseline in 12-72 hrs 88. Red hair coupled with female gender increases MAC 89. MAC values for inhaled agents are additive 90. Opioids synergistically reduced inhaled anesthetic requirements 91. Dose-response curves are steep therapeutic index is narrow lxviii. Define MAC = minimum alveolar concentration at 1 atm to prevent skeletal muscle movement in response to painful stimuli in 50% of patients lxix. MAC values for inhaled anesthetics are additive e.g. 0.5 MAC of N2O + 0.5 MAC of isoflurane has the same effect as 1 MAC of either anesthetic alone lxx. Opioids have a synergistic effect on inhaled anesthetics q. Complications associated with inhalation agent administration to include: lxxi. Cardiac dysrhythmia -- halothane has a risk of cardiac depression and VT 92. Halothane sensitizes heart to the arrythmogenic effects of catecholamines lxxii. Hepatic disease -- halothane has a risk of postoperative hepatic dysfunction lxxiii. Kidney injury 93. Enflurane is metabolized in liver but produces fluoride ions which are nephrotoxic 94. When sevoflurane is exposed to CO2 absorbents, it can produce compound A which is nephrotoxic lxxiv. Hypotension 95. Decreases in MAP are due to decreases in SVR with isoflurane, desflurane, and sevoflurane 96. Decreases in MAP are due to decreased inotropy and decreased CO in halothane lxxv. Nitrous oxide can increase MAP or have no effect lxxvi. Halothane can trigger malignant hypertension lxxvii. **Myocardial ischemic preconditioning occurs when** the myocardium has been briefly exposed to an ischemic event 97. Potassium channels tend to be hyperpolarized 98. When exposed to another ischemic event, the potassium channel doesn't react so heart is protected from sustained ischemic or hypoxic insult 99. Brief exposure to volatile inhalation agents appear to provide a similar protective effect r. Be able to discuss the influence of inhalation agents: lxxviii. Cardiovascular performance 100. Cardiac output w. Halothane decreases cardiac output and inotropy x. Cardiac output influences uptake the blood. Higher CO will result in more rapid uptake and slowing induction. Lower CO will result in less uptake in blood and faster induction 101. Isoflurane, desflurane, and sevoflurane increase HR 102. CVP will increase with halothane, isoflurane, and desflurane 103. Systemic vascular resistance y. Isoflurane, desflurane, and sevoflurane decrease SVR 104. Pulmonary vascular resistance z. All volatile agents have little to no effect on PVR a. N2O increases PVR and should avoided in PHTN lxxix. Respiratory dynamics 105. Rate and depth of ventilation b. Inhaled anesthetics increase the RR c. Inhaled anesthetics decrease Vt (except N2O) d. Inhaled anesthetics depress ventilation and blunt the ventilatory response to hypoxia and hypercapnia 106. Bronchiole smooth muscle tone/airways resistance e. sevoflurane produces bronchodilation lxxx. Volatile anesthetics decrease renal blood flow and GFR in a dose-dependent fashion. Preoperative hydration can reduce these effects lxxxi. Central nervous system effects 107. Cerebral blood flow f. Inhalation agents produce dose dependent increases in cerebral blood flow g. Increased cerebral blood flow causes increases in ICP h. Hyperventilation to a PaCO2 of 30 can counter the effects of increased ICP 108. EEG i. At MAC\