Week 4 Flashcards
Identify the pathophysiologic mechanisms that contribute to this patient’s symptoms of asthma, including early and late phase pulmonary changes.
Inhalation of allergen immediately triggers constriction of bronchial smooth muscle resulting in bronchospasm and a reduction in airflow. If the initial inflammatory response progresses, late phase bronchoconstriction increases as the result of interstitial fluid accumulating in and around the airway.
, justify why albuterol and not epinephrine is the preferred treatment for the relief of this patient’s bronchoconstriction
- Albuterol is a selective β2-adrenergic receptor agonist. Albuterol selectively binds β2-adrenergic receptors located on bronchial smooth muscle cells, couples to Gs-protein, stimulates adenylyl cyclase and increases intracellular cAMP, which inhibits myosin light chain kinase phosphorylation and relaxes airway smooth muscle. Epinephrine is a non-selective β1, β2, and α-adrenergic receptor agonist. It non-selectively binds multiple adrenergic receptor subtypes located on the cell surface of the myocardium (β1) as well as bronchial (β2) and vascular smooth muscles (α). Actions of epinephrine at the β1-adrenergic receptors in the myocardium are associated with increased risk of tachycardia, arrhythmias, and decreases in serum potassium levels. Additionally, actions of epinephrine at α-adrenergic receptors increase vascular resistance (vasoconstriction) with resultant (iatrogenic) hypertension and reduced pulmonary perfusion. - Selective β2 -adrenergic receptor agonists like albuterol do not have the β1- and α-adrenergic receptor-mediated adverse effects associated with epinephrine, and therefore albuterol has replaced epinephrine as the mainstay treatment for asthma
. Describe one lifestyle change to reduce exposure to potential allergens and briefly describe another lifestyle change to reduce the patient’s allergenic response.
- For indoor asthma triggers, frequent house-cleaning and use of HEPA (high-efficiency particulate absorbing, MERV 7+) air filters can reduce the amount of myriad allergens contained in house-dust. Dust mites frequently trigger symptoms in atopic patients, and removal of carpeting/curtains, use of allergen-proof bed covers, and regular washing of cloth (bedding; plush/stuffed toys; and other “fomites”) is recommended. - The ideal diet should emphasize cold-water fish for omega-3s and colorful fruits and vegetables for antioxidant phytonutrients (e.g., polyphenols). These foods help to reduce inflammation and oxidation, respectively.
Describe three different ways that the cells primarily responsible for maintaining the anti-inflammatory environment in the lungs during asthma might be altered compared to healthy individuals.
Alveolar macrophages (AMs) are the cells that are primarily responsible for maintaining the normally anti-inflammatory environment in the lung parenchyma (in healthy individuals). They do this in multiple ways, including the following: -production of inactive TGF-β, an important anti-inflammatory cytokine that inhibits activation of T cells and promotes differentiation of T cells to Tregs -expression of the IL-10 (another important anti-inflammatory cytokine) receptor, which is important for maintaining the anti-inflammatory phenotype in AMs -production of IL-10 -expression of CD200R, the receptor for CD200, the “don’t eat me signal” found on alveolar epithelial cells, which, when bound, decreases inflammation by downregulating pro-inflammatory cytokine production and increases anti-inflammatory cytokine production in AMs (by inhibiting NF-kB translocation to the nucleus)
Explain the mechanism for this patient with PE having hypoxemia.
The patient has hypoxemia as a result of inadequate pulmonary perfusion due to the presence of pulmonary emboli. This creates ventilation/perfusion (V/Q) inequality in which there is ventilation but no perfusion. The result is infinite V/Q and alveolar dead space in the affected distribution, which results in overall impairment of pulmonary gas exchange with a reduction in oxygen diffusion from the alveoli to the pulmonary capillaries, thus leading to the patient’s hypoxemia.
Outline why a patient with a PE would exhibit jugular venous distension.
The presence of pulmonary emboli significantly reduces the radius of the pulmonary vessels causing marked elevations in pulmonary vascular resistance. This increases the work of the right side of the heart, and in this patient, this excessive increase in right ventricular wall stress induces contractile failure. The resultant backup of blood from the right ventricle into the right atrium into the vena cava increases central venous pressure, which is further transmitted through the superior vena cava into the jugular veins that can be visualized as jugular venous distension (JVD / elevated jugular venous pressure).
Identify one acceptable pharmacologic agent for the initial (short-term) treatment of the patient’s acute emboli.
- Fondaparinux is an acceptable alternative to LMW heparin in non-pregnant patients, with a similar efficacy and safety profile (but at a markedly higher cost). - Low-molecular-weight (LMW) heparin, most commonly enoxaparin, is often chosen due to its higher rates of thrombus regression and lower rates of complications (recurrent thrombosis, major bleeding, and mortality) compared to unfractionated heparin. - Unfractionated heparin is the preferred anticoagulant for patients with severe renal failure, hemodynamic instability, and/or a high likelihood of a surgical procedure requiring rapid reversal of anti-coagulation.
Identify the most likely diagnosis and the expected changes in intrapleural/intrathoracic pressure and diaphragmatic motion resulting from the stab wound.
The patient is most likely to have developed a tension pneumothorax (potentially complicated by a hemothorax if a blood vessel is lacerated, with dullness to percussion over the lower lung field). The intrapleural and intrathoracic pressure become positive because of the connection to atmospheric pressure. The compromised integrity of the system results in alveolar collapse and depression of the hemidiaphragm due to the increased intrathoracic pressure.
Based on the location of the stab wound (left lateral chest) , identify the layers of the pleurae that could be disrupted by the stab wound. Describe the normal function of the pleural cavity and the effect the stab wound would have on this space
The layers of pleurae that could be disrupted include both the costal parietal pleurae and the visceral pleurae (with longer blade lengths). Between the parietal and visceral pleurae is a thin, serous fluid which acts as a lubricant – reducing friction as the two membranes slide across one another when the lungs expand and contract with respiration. The surface tension of the pleural fluid also couples the visceral and parietal pleura to one another, thus preventing the lungs from collapsing. Since the potential exists for a space between the two membranes, this area is called the pleural cavity or pleural space. The stab wound inflicted upon this patient would cause disruption of the pleural surface tension, increasing the intrapleural pressure and thus causing the lung to collapse
Describe the screening OSE findings that could be expected on a patient’s exam who has just been stabbed
- costal cage contour would feel depressed on the left side. - Acute tissue texture changes (warmth, bogginess, erythema) would likely be noted in the T2-T7 paraspinal area (sympathetic Viscerosomatic reflexes) and at the spinal level of the stab wound (sympathetic Somatosomatic reflexes). Acute tissue texture changes and somatic dysfunction may also be found at the Occiput (parasympathetic Viscerosomatic reflexes) and at the C3-C5 paraspinal area (thoracoabdominal diaphragm somatosomatic reflexes). Chapman’s reflexes may also be found anteriorly at the 2nd, 3rd, and 4th intercostal spaces and posteriorly at the T2-T4 transverse processes, representing the Bronchus, upper lungs, and lower lungs respectively.
Based on the patient’s diagnosis (idiopathic pulmonary fibrosis), predict the following results of her forced expiratory volume (FEV1), forced vital capacity (FVC), and FEV1/FVC and explain your answer.
Interstitial pulmonary fibrosis is a restrictive lung disease in which there is a decreased compliance with increased elastic recoil. Because of the lung’s increased elastic recoil pressure and low lung volumes, the patient’s FEV1 and FVC are reduced proportionally. As a result the FEV1/FVC could be normal or increased in this patient.
Based on the patient’s diagnosis (idiopathic pulmonary fibrosis), justify her reduced functional residual capacity (FRC).
FRC is that lung volume at which the inward recoil force of the lung is balanced by the outward recoil force of the chest wall at the end of expiration. FRC is reduced when lung compliance is reduced (as in this patient). This occurs because decreased lung compliance increases the inward recoil force at end-expiration to a level above the outward recoil force of the chest wall. This increased lung recoil force causes the lung-chest wall unit to move to a smaller volume where the inward lung recoil force is again equal to the outward chest wall recoil force.
Predict the appearance of a patient’s flow-volume during expiration and inspiration if he has emphysema. Correlate your answer to the patient’s underlying disease.
Chronic bronchitis and emphysema (COPD) are obstructive diseases that interfere with airflow. Emphysema is classically associated with high lung volumes, and COPD in general is associated with flow rates that are lower than normal (regardless of lung volume). Even though the lung volumes are high, there is still a reduction in the elastic recoil due to the destruction of the airways with a decrease in the number of small airways. During expiration, as the intrapleural pressure increases, there is less traction on these airways causing them to collapse and decrease the pressure gradient for flow. The result is a concave appearance on the effort-independence portion of the expiratory curve. During inspiration, the airways are tethered open by radial traction exerted by the surrounding alveolar walls. Therefore, the inspiratory curve may be normal or close to normal.
Describe why a patient with emphysema has a reduced forced vital capacity (FVC).
With COPD, there is greater difficulty in achieving high airflow rates during forced expiration. This is because of the destruction of the alveolar septal tissue, which reduces the elastic recoil of the lungs. This results in less traction to oppose dynamic compression and a reduction in the driving pressure of airflow. With each forced expiration, the intrapleural pressure becomes more and more positive, causing more and more dynamic compression of smaller airways, which results in the patient’s low FVC.
explain the mechanism responsible for the long-acting effects associated with tiotropium. Include the drug subclass and specific receptor subtypes affected.
Tiotropium is an anticholinergic / long-acting muscarinic antagonist (LAMA) that antagonizes cholinergic nerve-induced smooth muscle contractions. Tiotropium has equal affinity for muscarinic M1, M2, and M3 receptors, but the rate of tiotropium dissociation varies among the muscarinic receptor subtypes. The rate of tiotropium dissociation from M3 receptors is slow, whereas the rate of tiotropium dissociation from M1 and M2 receptors is rapid. Compared to short-acting antimuscarinic agents, the slow M3 receptor dissociation kinetics of tiotropium is associated with long-acting bronchodilation in patients with chronic obstructive pulmonary disease (COPD).
