Respiratory Flashcards
Conducting zone in the respiratory tree
The large airways consist of nose, pharynx, larynx, trachea, and bronchi. Small airways consist of bronchioles that further divide into terminal bronchioles (a large number of parallel creates the least resistance. They are responsible for warms, humidifies, and filters air but does not participate in gas exchange (anatomic dead space). Cartilage and goblet cells extend to the end of the bronchi. Pseudostratified ciliated columnar cells (clear mucus from lungs) extend to beginning of terminal bronchioles, then transition to cuboidal cells. Airway smooth muscle cells extend to the end of terminal bronchioles.
Respiratory zone
It is located in the lung parenchyma and consists of respiratory bronchioles, alveolar ducts, and alveoli. It participates in gas exchange. There are mostly cuboidal cells in respiratory bronchioles, then simple squamous cells up to the alveoli. Cilia terminate in the respiratory bronchioles. Alveolar macrophages clear debris and participate in immune responses.
Type I pneumocytes
They cover 97% of alveolar surfaces and line the alveoli. They are squamous; Thin is optimal for gas diffusion.
Type II pneumocytes
They secrete pulmonary surfactant, which decreases alveolar surface tension and prevents alveolar collapse (atelectasis). They are cuboidal and clustered. They also serve as precursors to type I cells and other type II cells. Type II cells proliferate during lung damage.
Club (Clara) cells
They are nonciliated, low columnar/cuboidal with secretory granules. They secrete a component of surfactant, degrade toxins, and act as a reserve cell.
Collapsing pressure (P)
P=(2 x surface tension)/radius. Alveoli have an increased tendency to collapse on expiration as radius increases (law of Laplace).
Surfactant
Pulmonary surfactant is a complex mix of lecithins, the most important of which is dipalmitoylphosphatidylcholine. Surfactant synthesis begins around week 26 of gestation, but mature levels are not achieved until around week 35. Lecithin to sphingomyelin ration is over 2 in amniotic fluid indicates fetal lung maturity.
Lung anatomy
The right lung has three lobes; Left has Less Lobes (2) and Lingula (homolog of the right middle lobe). The right lung is more common site for inhaled foreign body because the right main stem bronchus is wider and more vertical than the left. If you aspirate a peanut: while upright, it enters the lower portion of the right inferior lobe; while supine, it enters superior portion of the right inferior lobe. Instead of a middle lobe, the left lung has a space occupied by the heart. The relationship of the pulmonary artery to the bronchus at each lung hilum is described by RALS: Right Anterior, Left Superior.
Structures perforating the diaphragm
At T8, IVC passes through. At T10, esophagus and vagus (CN 10; 2 trunks) passes through. At T12, aorta (red), thoracic duct (white), azygos vein (blue) passes through (At T-1-2 its the red, white and blue). I (IVC) ate (8) ten (10) eggs (esophagus) at (aorta) twelve (12).
Innervation of the diaphragm
It is innervated by C3, 4, and 5 (phrenic nerve), which keeps the diaphragm alive. Pain from the diaphragm irritation (eg air or blood in the peritonial cavity) can be referred to shoulder (C5) and trapezius ridge (C3, C4).
Level of the common carotid bifurcation
Bifourcates at C4.
Level of the trachea bifurcation
Bifourcates at T4.
Level of the abdominal aorta bifurcation
Bifourcates at L4.
Inspiratory reserve volume (IRV)
Air that can still be breathed in after a normal inspiration.
Tidal volume (TV)
Air that moves into the lung with each quiet inspiration, typically around 500mL.
Expiratory reserve volume (ERV)
Air than can still be breathed out after a normal expiration.
Residual volume (RV)
The air in lung after maximal expiration. It cannot be measured on spirometry.
Inspiratory capacity (IC)
Inspiratory reserve volume (IRV) + tidal volume (TV)
Functional residual capacity (FRC
Expiratory reserve volume (ERV) + residual volume (RV). It is the volume of gas in lungs after normal expiration.
Vital capacity (VC)
Inspiratory reserve volume (IRV) + tidal volume (TV) + expiratory reserve volume (ERV). It is the maximum volume of gas that can be expired after a maxima inspiration.
Total lung capacity (TLC)
Inspiratory reserve volume (IRV) + tidal volume (TV) + expiratory reserve volume (ERV) + residual volume (RV). It is volume of gas present in lungs after a maximal inspiration.
Determination of physiologic dead space
Vd=physiologic dead space= anatomic dead space of conducting airways plus alveolar dead space. The apex of a healthy lung is the largest contributor of alveolar dead space. Volume of inspired air that does not take part in gas exchange. Vd = Vt x (PaCO2 -PeCO2)/PaCO2. Vt = tidal volume. PaCO2= arterial PCO2. PeCO2 = expired air PCO2. (Taco, Paco, PEco, Paco is the order of variables in the equation).
Minute ventilation (Ve)
Total volume of gas entering lungs per minute. Ve= Vt x respiratory rate (RR). Vt = tidal volume.
Alveolar ventilation (Va)
Volume of gas per unit of time that reaches the alveoli. Va=(Vt-Vd) x RR.
Elasticity of the lung and chest wall
Elastic recoil is the tendency for lungs to collapse inward and chest wall to spring outward. At functional residual capacity, the inward pull of the lung is balanced by the outward pull of the chest wall, and system pressure is atmospheric. Elastic properties of both the chest wall and lungs determine their combined volume. At functional residual capacity, airway and alveolar pressures are 0, and intrapleural pressure is negative (which prevents a pneumothorax). Pulmonary vascular resistance is at a minimum.
Compliance of the lung and chest wall
Is the change in lung volume for a given change in pressure. It decreases in pulmonary fibrosis, pneumonia, pulmonary edema. It increases in emphysema and normal aging.
Hemoglobin
Hemoglobin is a tetramer (consisting of 4 subunits), with each subunit containing a centric heme molecule. Each heme molecule can carry 1 oxygen molecule. Hemoglobin has several variants including: Hemoglobin A (α2β2) which is found in adults; Hemoglobin A2 (α2δ2), which is also found in adults but in lesser quantities; Hemoglobin F (α2γ2), found predominately in fetal life.
Taut vs relaxed hemoglobin
Hemoglobin’s subunits switch between two conformations with different affinities for oxygen: The Taut (T) form has a low affinity for oxygen and the Relaxed (R) form has a high affinity for oxygen (over 300x). When two oxygen molecules are bound to hemoglobin in the taut conformation, its conformation switches to the relaxed form so that all four heme sites may be filled, occurring in a high oxygen tension environment (e.g. lungs). The relaxed conformation of hemoglobin switches to the taut conformation under times of low oxygen tension, such as in the peripheral tissues where oxygen needs to be unloaded. Hemoglobin acts a buffer for H ions. Hemoglobin modifications (eg methemoglobin and carboxyhemoglobin) lead to tissue hypoxia from decreased O2 saturation and decreased O2 content.
Specific conditions favor the taut hemoglobin conformation over the relaxed conformation
Specific conditions favor the taut hemoglobin conformation over the relaxed conformation, allowing oxygen to be unloaded peripherally and moving the oxygen dissociation curve to the right: CO2 allosterically binding the N-terminus; Acidic environments (i.e. low pH); 2,3-DPG (Fetal Hb has a lower affinity than adult Hb and thus has a higher affinity for O2), produced during glycolysis and stabilizes the taut conformation; Elevation by decreasing oxygen tension; Temperature elevation. Mnemonic: A CADET faces right.
Carboxyhemoglobin
Carboxyhemoglobin, resulting from carbon monoxide poisoning or chronic tobacco smoking, produces a cherry-red appearance of the skin typically in deceased patients. Treatment for carboxyhemoglobinemia is 100% O2 or hyperbaric O2.
Methemoglobinemia
Methemoglobinemia results from oxidation of ferrous iron (Fe2+) to ferric iron (Fe3+) leading to a reduced affinity for oxygen. Classic findings for patients with methemoglobinemia include cyanosis and chocolate colored blood. The most common chemicals and drugs that may cause acquired methemoglobinemia: Anesthetics (e.g. benzocaine), Benzenes, Antibiotics (e.g. dapsone, chloroquine, sulfonamides), Nitrites (used as additives to prevent meat from spoiling). Methemoglobinemia is treated with: Methylene blue, acting as a cofactor to propagate the methemoglobin to hemoglobin transition; Vitamin C, which may be beneficial by acting as an electron donor to limit reactive oxygen species formation or by altering iron levels
Myoglobin
Myoglobin is similar in structure to hemoglobin, but is a monomer.
Oxygen-hemoglobin dissociation curve
The oxygen-hemoglobin dissociation curve is a plot of percent saturation of hemoglobin as a function of pO2. The curve has a sigmoidal shape, which reflects the positive cooperativity of hemoglobin. Positive cooperativity of hemoglobin refers to the fact that when each O2 binds hemoglobin, the resulting conformational change in the hemoglobin molecule causes an increase in its affinity for additional O2 molecules (until fully saturated). The p50 of a curve (pO2 at which 50% saturation is achieved) can be used to compare different curves with one another. The normal value for p50 is 26.7mmHg.
Right shift of the hemoglobin dissociation curve
When P50 is greater than 26.7mmHg, the hemoglobin dissociation curve is said to exhibit a “right shift.” With a right shift, hemoglobin has less affinity for O2, which facilitates unloading of O2 in the tissues. Right shift occurs with: Increased temperature (ex: tissues with increased metabolic activity); Increased [H+] (decreased pH); Higher altitude; Increased [2,3-BPG] (aka 2,3-DPG); CHRONIC anemia, which causes an increase in [2,3-BPG]. The factors that cause a right shift in the oxygen hemoglobin dissociation curve can be remembered with mnemonic (CADETs face right): CO2 (increased [CO2] ); Acidosis, Anemia; 2,3-DPG; Elevation; Temperature increase.
Left shift of the hemoglobin dissociation curve
A “left shift” of the oxygen hemoglobin dissociation curve refers to when the p50
Oxygen content of blood
O2 content = (O2 binding capacity x % saturation) + dissolved O2. Normally 1 g Hb can bind 1.34 mL O2. The normal Hb amount in the blood is 15g/L. Cyanosis results when deoxygenated Hb over 5g/dL. O2 binding capacity is about 20.1 mL O2/dL. With a decrease in Hb there is a decrease in O2 content of arterial blood but no change in O2 saturation and arterial PO2. O2 delivery to tissue=cardiac output x O2 content of blood.
Oxygen content with CO poisoning
Hb concentration is normal, % O2 sat of Hb decreases (CO competes with O2), dissolved O2 (PaO2) is normal, and total O2 content is decreased.
Oxygen content with anemia
Hb concentration is decreased, % O2 sat of Hb normal, dissolved O2 (PaO2) is normal, and total O2 content is decreased.
Oxygen content with polycythemia
Hb concentration is increased, % O2 sat of Hb normal, dissolved O2 (PaO2) is normal, and total O2 content is increased.
Pulmonary circulation
There is normally a low-resistance, high compliance system. PO2 and PCO2 exert opposite effects on pulmonary and systemic circulation. A decrease in PAO2 causes a hypoxic vasoconstriction that shifts blood away from poorly ventilated regions of lung to well ventilated regions of the lung.
Cor pulmonale
A consequence of pulmonary hypertension is cor pulmonale and subsequent right ventricular failure (jugular venous distention, edema, and hepatomegaly.
Perfusion limited gases
Some gases diffuse so rapidly across the alveolar membrane that their diffusion into blood is only limited by the perfusion of the alveoli. Such gases include O2 (in healthy lungs), CO2, and N2O and are referred to as “perfusion limited.” Upon inhalation, these gases equilibrate with the blood early along the total length of the pulmonary capillary, and diffusion can only be increased if blood flow increases. Gases that diffuse slowly across the alveolar membrane and do not equilibrate in the time that the blood traverses the pulmonary capillary are said to be “diffusion limited.” Such gases include CO, as well as O2 in the setting of emphysema or pulmonary fibrosis.
Fick’s law
The diffusion of gas across the alveolar membrane into the blood can be represented by Fick’s law of diffusion: Vgas = (A/T) x Dk x ΔP. A = total diffusing surface area of alveoli. T = alveolar wall thickness. Dk = diffusion constant (based upon the solubility and molecular weight of the gas). ΔP = difference in the partial pressures of the gas across the membrane (P1 - P2)
Pulmonary Vascular Resistance (PVR)
Pulmonary Vascular Resistance (PVR) can be calculated with the following equation: PVR = ( P pulm artery - P left atrium ) / CO. This equation is a derivative of the equation R = ΔP/Q. Ppulm artery = pulmonary artery pressure. Pleft atrium = capillary wedge pressure. CO = cardiac output. R = resistance. Q = flow. ΔP = change in pressure over the length of the vessel. Remember: ΔP = Q x R, so R= ΔP/Q. R=8nl/Pi to the fourth. n = viscosity of blood; 1=vessel length; r=vessel radius.
Alveolar gas equation
The alveolar gas equation is: PAO2 = PiO2 – (PaCO2/R). PAO2 = alveolar PO2 in mmHg. PiO2 = pressure of inspired oxygen in mmHg (can sometimes be approximated to 150). PaCO2 = arterial PCO2 in mmHg. R = respiratory quotient, which = (CO2 produced)/(O2 consumed). The alveolar gas equation allows us to calculate the PAO2 from an arterial blood gas sample, which can be used to ultimately estimate the A-a gradient..
Calculating the pressure of inspired oxygen
When breathing environmental air at sea level, the PiO2 can be approximated to ~150. However, if there is a known altitude change, to calculate the altitude adjusted PiO2: Take the atmospheric pressure (ex: 760 if at sea level) and subtract the H2O vapor pressure (normally ~ 47) which is the moisture added to inspired air as it is humidified by the respiratory mucosa. For example, at sea level this would be: (760 – 47) = 713. Then multiply the result by the FiO2, which is the percentage of O2 in the air (normally 21%). So continuing with the example at sea level, (713) x (.21) = 149.73. Therefore, the FiO2 of room air is 0.21 and the PiO2 of room air is 150 mmHg.
A-a gradient
The A-a gradient is a value that reflects the integrity of oxygen diffusion across the alveolar and pulmonary arterial membranes. The A-a gradient can be calculated by subtracting the arterial partial pressure of oxygen from the alveolar partial pressure of oxygen (PAO2 – PaO2). PAO2 = alveolar oxygen pressure. PaO2 = arterial oxygen pressure. A normal resting A-a gradient in healthy middle aged adults ~ 5-10 mmHg. A-a gradient is normal during conditions of hypoxia caused by Hypoventilation, Decreased FiO2 (experimentally, or at high altitude due to decreased PiO2). Increased A-a gradient may occur in: Shunting, V/Q mismatch, Aging, and Diffusion impairments (ex: interstitial fibrosis or pulmonary edema).
Hypoxemia
A decrease in PaO2. Causes with a normal A-a gradient include high altitude and hypoventilation (eg opioid use). Causes with an increased A-a gradient includes V/Q mismatch, diffusion limitation, right to left shunt.
Hypoxia
A decrease in O2 delivery to tissue. Causes include decreased cardiac output, hypoxemia, anemia, and CO poisoning.
Ischemia
Loss of blood flow. Causes include impeded arterial flow and decreased venous drainage.
V/Q mismatch
Ideally, ventilation is match to perfusion (ie V/Q=1) for adequate gas exchange. Lung zones: V/Q at the apex of lung=3 (wasted ventilation); V/Q at base of lung=0.6 (wasted perfusion). Both ventilation and perfusion are greater at the base of the lung than at the apex of the lung. With exercise (increased cardiac output), there is vasodilation of apical capillaries causes V/Q ratio approaches 1. Certain organisms that thrive in high O2 (eg TB) flourish in the apex.
Shunt
When V/Q=0, there is an airway (Oirway) obstruction (shunt). In a shunt, 100% O2 does not improve PaO2.
Physiologic dead space
When V/Q=infinity, there is a blood flow obstruction (physiologic dead space). Assuming that there is less than 100% dead space, 100% O2 improves PaO2.
Zone 1 of the lung
It is in the apex. PA is greater than Pa, which is greater than Pv. A slight decrease in V and a large decrease Q causes V/Q to increase.
Zone 2 of the lung
Pa is greater than PA, which is greater than Pv.
Zone 3 of the lung
Pa is greater than Pv, which is greater than PA. A slight increase in V and a large increase in Q causes V/Q to decrease.
CO2 transport
CO2 is transported from tissues to lungs in 3 forms: HCO3 (90%); Carbaminohemoglobin or HbCO2 (5%). CO2 bound to Hb at N-terminus of globin (not heme). CO2 binding favors the taut for (O2 is unlocked); Dissolved CO2 (5%).
Haldane effect
The Haldane effect describes the property of hemoglobin that promotes the release of bound H+ in the presence of increased [O2]. The binding of O2 to hemoglobin makes the Hgb-H+ bond less stable, thus promoting the release of H+. The resulting increase in free [H+] facilitates CO2 formation and expiration at the lungs via the reaction catalyzed by carbonic anhydrase (H+ + HCO3- -> H2CO3 -> CO2 + H2O). This reaction occurs in RBCs. The majority of blood CO2 is carried as HCO3 in the plasma.
Bohr effect
The Bohr effect describes the decrease in hemoglobin’s affinity for oxygen in the presence of increased CO2 and decreased pH. This occurs in peripheral tissue.
Response to high altitude
A decrease atmospheric oxygen (PO2) decreases PaO2, which increases ventilation thus decreasing PaCO2). There is also a chronic increase in ventilation. There is an increase in erythropoietin, which increases hematocrit and Hb (chronic hypoxia). It also increases 2,3-BPG, which binds to Hb so that Hb releases more O2. There are cellular changes like increased number of mitochondria. There is an increase in renal excretion of HCO3 to compensate for respiratory alkalosis (can be augment with acetazolamide). Chronic hypoxic pulmonary vasoconstriction results in RVH.
Response to exercise
There is increased CO2 production, increased O2 consumption, and increased ventilation rate to meet O2 demand. V/Q ratio from apex to base becomes more uniform. There is increased pulmonary blood flow due to increased cardiac output. There is also a decrease pH during strenuous exercise (secondary to lactic acidosis). There is no change in PaO2 and PaCO2, but there is an increase in venous CO2 content and a decrease in venous O2 content.
Rhinosinusitis
Obstruction of sinus drainage into nasal cavity causing inflammation and pain over affected area (typically maxillary sinuses in adults). The most common acute cause is viral URI, which may cause a superimposed bacterial infection, most commonly S. pneumoniae, H influenzae, M. catarrhalis.
Epistaxis
Nose bleed. It most commonly occurs in the anterior segment of the nostril (Kiesselbach plexus). Life threatening hemorrhages occur in the posterior segment (sphenopalatine artery, a branch of maxillary artery).
Deep venous thrombosis
A blood clot within a deep vein causes swelling, redness, warmth, and pain. It is predisposed by Virchow triad (SHE): Stasis. Hypercoagulability (eg defect in the coagulation cascade proteins, such as factor V Leiden. Endothelial damage (exposed collagen triggers clotting cascade). Approximately 95% of pulmonary emboli arise from proximal deep veins of lower extremity. The Homan sign is calf pain with dorsiflexion of the foot. Treatment is unfractionated heparin or low molecular weight heparins (eg enoxaparin) for prophylaxis and acute management. Use oral anticoagulants (eg warfarin, rivaroxaban) for long-term prevention.
Pulmonary emboli
V/Q mismatch causes hypoxemia, which leads to respiratory alkalosis. Symptoms include sudden-onset dyspnea, chest pain, tachypnea, tachycardia. It may also present as sudden death. Lines of Zafn are interdigitating areas of pink (platelets, fibrin) and red (RBCs) found only in the thrombi formed before death, which helps in distinguish pre and postmortem thrombi. Types include Fat, Air, Thrombus, Bacteria, Amniotic fluid, and Tumor. An embolus moves like a FAT BAT. CT pulmonary angiography is imaging test of choice for PE (look for filling defects).
