Week 6 Flashcards
Describe the most likely pulmonary disease based on this patient’s clinical features (worsening dyspnea on exertion over an 18-month period. He has lost 15 pounds unintentionally during this time. He has a 50 pack-year history of smoking. He demonstrates pursed-lip breathing, but no acrocyanosis) and pulmonary function findings. ( (FEV1) 57%, (FVC) 65% , FEV1/FVC ratio 49% with a non-significant response to bronchodilators. A chest radiograph reveals large lung volumes, a large retrosternal airspace, and a low and flattened diaphragm.
the most likely pulmonary disease is emphysema. pathologic changes produce a decrease in the efficiency of the flattened diaphragm resulting in weight loss due to increased work of breathing. The pursed lip breathing technique is an attempt to maintain positive end-airway pressure and prevent early dynamic compression due to septal destruction. These patients (in contrast to patients with chronic bronchitis) rarely present with cyanosis. The patient’s 50-pack-year smoking history is the most likely pathogenetic factor for his emphysema (smoking is the cause of COPD in 80% of cases). The reduced flow rates in conjunction with a reduced FEV1 and FVC is consistent with an obstructive disorder. (Asthma is ruled out because no change is seen in the FEV1% in response to bronchodilators).
Explain how the morphologic features in his distal airways caused by emphysema lead to functional airflow obstruction
Functional airflow obstruction occurs due to loss of elastic tissue in the walls of alveoli in emphysema. Distal airways are normally held open by the elastic recoil of the lung parenchyma. Loss of elastic tissue in alveolar walls surrounding respiratory bronchioles reduces radial traction, causing respiratory bronchioles to collapse during expiration
Explain why a patient with emphysema would have impaired pulmonary gas exchange.
This patient’s emphysema is associated with a destruction in alveolar septal tissue and alveolar vessels increasing alveolar dead space. The result is alveolar-capillary units with a high V/Q or ventilation but no perfusion. In addition, the damage to the alveolar-capillary units reduces the surface area for diffusion. This decreases the volume of air diffusing from the alveoli into the capillaries. Together, the V/Q mismatch and loss of surface area impairs gas exchange
On exam, his PCP observes the Hoover sign on deep inspiration. Explain the anatomic changes related to advanced COPD that have led to the development of this physical exam finding.
Structurally, the diaphragm in the COPD patient creates a straighter line between the subcostal margins at a lower level in the thorax, thereby significantly reducing the zone of apposition as well as the overall surface area of the muscle.
When attempting deep inhalations from the flattened (end-stage) state with a marked reduction in the zone of apposition, the subcostal margin is drawn inward during diaphragmatic contraction because the diaphragm cannot flatten any further. This paradoxical motion is termed the Hoover sign
The patient reports persistent symptoms of exertional dyspnea and functional limitation of activities despite use of a rescue inhaler. The physician prescribes salmeterol. Describe the mechanism(s) and site(s) of action of salmeterol-mediated bronchodilation and include the drug’s subclass.
Long-acting β2-adrenergic agonists (LABAs) such as salmeterol bind to β2-adrenergic receptors that are abundant on airway smooth muscle cells. Agonist binding changes the conformation of the receptor, which activates heteromeric Gαs-proteins to stimulate adenylyl cyclase and increase the formation of intracellular cAMP to increase the activity of protein kinase A (PKA). In the smooth muscle, cAMP inhibits myosin light chain kinase, inducing relaxation of airway smooth muscle. In addition, LABAs also inhibit the release of bronchoconstricting mediators from mast cells.
Explain why the physician prescribed inhaled budesonide in combination with an inhaled long-acting β2-adrenergic agonist (LABA). Include budesonide’s drug subclass and mechanism(s) of action in your response.
The physician prescribed an inhaled corticosteroid (ICS), budesonide, in combination with a long-acting β2-adrenergic agonist (LABA, such as salmeterol) because prolonged bronchodilation can mask the symptoms of bronchial inflammation and consequently increase the risk of COPD exacerbations. [Additionally, corticosteroids may potentiate the effects of β agonists on bronchial smooth muscle and prevent and reverse β receptor desensitization in airways, as has been demonstrated in vitro and in vivo.] In addition, controller medications such as salmeterol have a longer duration of action (12 h) compared to short acting β2-adrenergic agonists (4-6hr), which helps to increase patient compliance and decrease the incidence of COPD exacerbations.
Corticosteroids, like inhaled budesonide, affect gene transcription by binding nuclear glucocorticoid receptors, increasing the transcription of several anti-inflammatory genes and suppressing transcription of many inflammatory genes (e.g. cyclooxygenase). They also directly inhibit phospholipase A2 (PLA2), an arachidonic acid precursor, to further reduce the synthesis of inflammatory mediators. Corticosteroids inhibit inflammatory cell recruitment and infiltration/structural cell damage in the airway.
A 52-year-old male presents to his family physician with a six-month history of progressively worsening dyspnea on exertion, dry cough, and chest discomfort. He denies fever, chills, recent sick contacts, or any known exposures to tuberculosis. He has a 30 pack-year history of smoking and works in construction. Chest X-ray reveals bilateral linear densities in the lower lobes with no areas of consolidation. Sputum gram stain and cultures are negative.
High-resolution CT scan demonstrates nodular densities in the upper lobes and the hilum. The patient’s symptoms improve significantly with an empirical course of corticosteroid therapy. Why is this NOT Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia?
The HRCT findings note upper lobe and hilar involvement, not typical of IPF/UIP which would show basilar, peripheral, and paraseptal predominance. Also, the patient improved with steroids, which would typically have no effect on IPF/UIP.
escribe how crystalline silica particles can cause pulmonary effects.
Cutting, grinding, or drilling silica (SiO2 – found in over 95% of the earth’s crust) releases crystalline particles that may be inhaled during quarrying, mining, sandblasting, and other industrial/commercial activities. Silica particles are toxic and provoke a severe fibrous reaction consisting of concentric whorls of dense collagen fibers in the lung. Heavy and/or prolonged silica inhalation may induce pulmonary fibrosis, with a restrictive pattern of pulmonary function, severe dyspnea and hypoxemia with physical exertion (exercise), and a reduced diffusing capacity (DLCO).
explains the utility of CPAP for obstructive sleep apnea. Relate the pathophysiology of her condition to the mechanism of action of CPAP.
Obstructive sleep apnea (OSA) occurs because the soft tissues of the upper airway – particularly the soft palate, tongue, and lateral pharyngeal wall – lack the support framework of cartilaginous rings found lower in the airway. This renders the upper airway susceptible to collapse. Ordinarily, the pharyngeal dilator muscles maintain a patent (open) airway, but during sleep, these muscles become less active. When pressure from the surrounding (extraluminal) soft tissues is combined with negative airway (luminal) pressure during inspiration, the balance in pharyngeal transmural (transpharyngeal) pressure shifts toward upper airway obstruction (collapse).
Because OSA patients tend to have excessive upper airway soft tissue (e.g., larger tongues, longer soft palates, and increased neck circumference due to obesity), they typically require a higher airway (luminal) pressure to maintain upper airway patency. Continuous Positive Airway Pressure (CPAP) delivers a fixed pressure during both inspiration and expiration that counteracts the collapse of the soft palate (retropalatal), tongue (retroglossal), and lateral pharyngeal walls (parapharyngeal fat pads).
A basic metabolic panel (BMP) reveals a bicarbonate level of 32 mmol/L (22-29 mmol/L), but pulmonary function testing appears normal. Name the most likely condition causing the patient’s hypercapnia, identify one possible mechanism of pathogenesis, and identify one potential treatment
This patient’s hypercapnia is most likely due to Obesity Hypoventilation Syndrome (OHS).
Several mechanisms may be contributing to the patient’s OHS; one of the following is an acceptable response:
- Obesity directly impairs respiratory system mechanics and increases the work of breathing.
- Obstructive sleep apnea triggers recurrent pulmonary hypoxia leading to reactive oxygen species and inflammation.
- Leptin resistance (from obesity) blunts the central hypercapnic and hypoxic ventilatory drive.
The typical management of OHS includes weight loss (to reduce obesity) and treatment of underlying OSA using CPAP (Continuous Positive Airway Pressure).
Explain why patient with untreated OSA has right-sided heart failure
This patient has pulmonary hypertension as a result of structural changes in her pulmonary vasculature causing increased pulmonary vascular resistance. This vascular remodeling is most likely a result of obstructive sleep apnea, with repetitive nocturnal hypoxia during apneic episodes while sleeping. In addition, she also appears to be manifesting signs of obesity hypoventilation syndrome with further (diurnal) hypoxemia during the day. The increased afterload in the pulmonary arteries 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.
Explain the rationale for prescribing sildenafil for patient’s with pulmonary HTN. Include the drug subclass, mechanism of action, and site of action in your response.
Due to the enrichment of phosphodiesterase-5 (PDE-5) in pulmonary vascular beds, PDE-5 inhibitors such as sildenafil (and tadalafil) induce vasodilation and reductions in pulmonary hypertension. PDE-5 inhibitors potentiate the actions of NO in pulmonary vascular beds by inhibiting PDE-5-mediated degradation of cGMP within the pulmonary vasculature. cGMP activates myosin light chain phosphatase to elicit smooth muscle relaxation and vasodilation that subsequently facilitates relief of pulmonary arterial hypertension.
