Describe the underlying pathology of COPD and the common pathological characteristics of the condition. Discuss the impact these pathological changes have on normal function, including how alveolar ventilation might be different in Mr Wenham compared to a normal individual.
The hallmark pathological attributes of chronic obstructive pulmonary disease (COPD) are one, poorly reversible airflow obstruction and two, a progressive atypical inflammatory response within the lungs. The abnormal inflammatory response denotes the responses of the innate and adaptive immune systems to long-standing exposure to noxious gases and particles especially cigarette smoke. Notably, all cigarette smokers have some degree of inflammation in their lungs. Those who develop COPD, however, have a heightened or atypical response to inhalation of toxic agents. This enhanced response can result in emphysema, chronic bronchitis, and bronchiolitis. Emphysema is due to tissue destruction while chronic bronchitis is due to hypersecretion of mucus. Bronchiolitis is due to inflammation and fibrosis in the small airways that occurs as a result of disruption of the normal defense and repair mechanisms. These pathological alterations lead to increased airflow resistance in the small airways, lung compliance, trapping of air, and progressive obstruction to airflow (MacNee, 2006).
COPD is marked by increased numbers of inflammatory cells that are macrophages, neutrophils, and T-lymphocytes in the lungs. These cells produce a variety of inflammatory mediators and cytokines take part in the inflammatory process. The two other processes involved in the pathophysiology of COPD are protease and antiprotease imbalance and oxidative stress in the lungs. The protease and antiprotease imbalance results from enhanced production/activation of proteases and reduced production/inactivation of antiproteases. Cigarette smoke and resultant inflammation produce oxidative stress. This oxidative stress primes a number of inflammatory cells to produce several proteases and at the same time inactivates a number of antiproteases through oxidation. The increase in oxidative stress in COPD is due to oxidants from cigarette smoke as well as reactive nitrogen and oxygen species elicited by inflammatory cells. The increase in oxidants leads to an oxidant-antioxidant imbalance and oxidative stress. Oxidative stress can stimulate mucus production or lead to the inactivation of proteases. In addition, it can enhance inflammation by increasing activation of transcription factor and in effect, gene expression of mediators of inflammation (MacNee, 2006).
The pathogenic mechanisms described above lead to pathological changes that in turn lead to physiological abnormalities. Resultant physiological anomalies include hypersecretion of mucus and ciliary dysfunction, obstruction of airflow and hyperinflation, abnormalities in gas exchange, pulmonary hypertension, and lastly, systemic effects. Hypersecretion of mucus causes a chronic productive cough and is a characteristic feature of chronic bronchitis. Mucus hypersecretion occurs as a result of squamous metaplasia and an increase in the number of goblet cells and size of submucosal glands of the bronchial secondary to protracted irritation by noxious gases and particles. Ciliary dysfunction results from squamous metaplasia involving epithelial cells and to mucociliary escalator dysfunction and difficulties in expectoration. Airflow obstruction occurs mostly in the small conducting airways. It is due to airway remodeling as a result of inflammation and narrowing and presence of inflammatory exudates within the small airways. Loss of the elastic recoil of the lungs secondary to tissue destruction of the alveolar walls as well as destruction of alveolar support also contributes to airflow obstruction. Airway obstruction leads to progressive trapping of air during expiration. This results in hyperinflation and dynamic hyperinflation at rest and during exercise respectively. The two features cause breathlessness and exercise intolerance. Gas exchange abnormalities occur in advanced COPD. They are characterized by arterial hypoxemia that can or fail to be accompanied by hypercapnia. They are caused by regional imbalances in ventilation and perfusion that result from destruction of alveoli as well as pulmonary vasculature. This destruction reduces the surface area available for diffusion of air. Breathlessness and exercise intolerance are also caused by pulmonary hypertension and impairments in cardiac function in advanced disease. Pulmonary hypertension develops in late disease as a result of arterial constriction secondary to hypoxia, endothelial dysfunction, remodeling of pulmonary arteries, and destruction of pulmonary capillary bed. Changes in the structure of the pulmonary arterioles cause persistent pulmonary hypertension as well as right ventricular hypertrophy and dysfunction (cor pulmonale). Systemic inflammation in COPD causes wasting and dysfunction of skeletal muscles. Easy fatiguability of skeletal muscles is posited to be one of the causes of dyspnea in COPD. Acute exacerbations of COPD are caused by bacterial or viral infections, changes in ambient temperature, and air pollution (Brashier and Kodgule, 2012).
2. Discuss why you would administer salbutamol and describe how it works at the cellular level.
Salbutamol is a β2 receptor agonist. It stimulates β2 adrenoreceptors within the airways leading to the generation of cyclic AMP. This reduces intracellular calcium producing bronchodilation. Calcium is needed for constriction of bronchial smooth muscles. An increase in cyclic AMP also prevents the degranulation of mast cells. The rationale for administration of salbutamol to this patient is to produce bronchodilation and in effect, an improvement in the patient’s dyspnea. Indeed salbutamol has a fast onset of action and is selective in its action hence it is preferred for rescue of symptoms in airway diseases. Bronchodilators are the mainstay in the management of COPD (Cazzola, Page, Calzetta and Matera, 2012).
3. Discuss why they would take an arterial blood gas and explain what the results mean and how they relate to the pathophysiology you described.
Analysis of arterial blood gases is necessary in COPD exacerbations to determine the degree of airflow obstruction, ventilation-perfusion mismatch, and need for domiciliary oxygen. Airflow obstruction in mild exacerbations is either unchanged or increased slightly. Severe exacerbations, however, lead to worsening of gas exchange as well as respiratory muscle fatigue. Alveolar hypoventilation and respiratory muscle fatigue contribute to hypoxemia, hypercapnia, and respiratory acidosis. The latter can cause severe respiratory failure and death. The patient’s arterial blood gases show that he has hypercapnia (PaCo2 100 mmHg) and respiratory acidosis (pH of 7.12). These findings indicate the presence of alveolar hypoventilation and an increased imbalance in ventilation-perfusion. The two can be due to inflammation of the airway, edema, hypersecretion of mucus, bronchoconstriction, and pulmonary vasoconstriction (Brashier and Kodgule, 2012).
4. Overview the normal physiological control of breathing. Then, identify and discuss the issues surrounding the use of supplemental oxygen therapy in patients with severe exacerbations of COPD. What problems can it cause and why?
The respiratory center is found in the medulla oblongata of the brain stem. It initiates normal breathing that is quiet rhythmic breathing at rest or during sleep. The respiratory center contains two groups of neurons that are the ventral and dorsal groups. The dorsal group is also referred to as the inspiratory center is the respiratory ‘pacemaker’. It is uncertain whether these neurons are self-excitatory. In the absence of other influences, these group of neurons switch on and off for approximately 2 and 3 seconds respectively. The neurons in the medullary inspiratory center are linked to lung muscles. They stimulate the nerves of inspiratory muscles, phrenic nerve of the diaphragm as well as intercostal nerves that innervate the external intercostal muscles. Contraction of these muscles leads to expansion of the thorax and air is drawn into the lungs. The muscles relax when the neurons of the inspiratory center are inactive. Relaxation of the muscles causes expiration to occur passively. The respiratory rate and depth of each inspiration are determined by the amount of time the respiratory center is on and strength of nervous stimulus to lung muscles respectively. The ventral group of neurons in the medullais mostly active during forced respiration. They stimulate muscles involved in forced expiration and inspiration such as the internal intercostal muscles and abdominal muscles. The above breathing is influenced by several influences that include the pons, higher brain centers, receptors in the lungs, and chemical influences. Centers in the pons, the pontine respiratory group of neurons, fine-tune breathing and prevent overinflation of the lungs by constantly sending inhibitory signals to the medullary inspiratory center to limit the length of time of inspiration. Stretch receptors and receptors to irritants found in the lungs influence the respiratory center through the vagus nerve. Higher brain centers such as the limbic system and hypothalamus can alter the respiratory rate and depth by influencing the medullary respiratory center or the pons. The cortex, on the other hand, influences breathing by sending impulses directly to inspiratory muscles. Central and peripheral chemoreceptors respond to chemical changes in blood and cerebrospinal fluid. They then influence the medullary respiratory center and pons to adjust the respiratory rate and depth as appropriate (Rhoades and Bell, 2009).
On the issue of oxygen, supplemental oxygen should be administered judiciously to patients with COPD. Destruction of alveoli as well as the pulmonary vasculature in COPD decreases the surface area available for air-diffusion causing a chronic hypoxic and hypercapnic state. Chronic retention of carbon dioxide, on the other hand, reduces the sensitivity of central chemoreceptors in the brain stem which then cease to be the primary mechanism for respiratory drive. Respiration in COPD is instead driven by hypoxia via peripheral chemoreceptors in the aortic arch and carotid arteries. The hypoxia additionally causes vasoconstriction of pulmonary capillaries which redirect blood away from alveoli that are poorly ventilated. Aggressive correction of hypoxia in patients with COPD with high flow oxygen particularly during exacerbations decreases the respiratory drive in such patients which can be catastrophic. This is because blunting of the hypoxic respiratory drive can lead to hypoventilation and retention of carbon dioxide (Jindal, 2008).
5. When considering his blood gas analysis, do you think it is a good idea to remove Mr. Wenham’s oxygen and have him just breathing air? Provide an argument supporting why it is or why it is not.
In view of the results of the patient’s blood gas analysis, it is a good idea to stop administration of supplemental oxygen to the patient. The goal of supplementation of oxygen is usually to maintain a partial pressure of oxygen of 55-60 mmHg that corresponds to an Spo2 of 90%. The patients Pa02 is 100 mmHg. This implies that that the patient has received too much oxygen and as already discussed, this can precipitate retention of carbon dioxide, hypoventilation, and respiratory failure. Indeed the patient is already experiencing retention of carbon dioxide as his PaCo2 is too high at 110 mmHg. His blood PH of 7.12 also shows he is experiencing respiratory acidosis (Brashier and Kodgule, 2012; Jindal, 2008).
6. What is BIPAP? How might BIPAP help to improve Mr. Wenham’s clinical condition?
BIPAP is an acronym for bilevel positive airway pressure. It is a form of positive noninvasive pressure ventilation. Noninvasive pressure ventilation refers to a ventilation modality that mechanically supports respiration without intubation or presence of a surgical airway. In BIPAP, a pressure-cycled machine called BIPAP delivers intermittent positive airway pressure that provides ventilator support for patients using a face or nasal mask. Increased pressure levels assist ventilation during inspiration by reducing CO2 levels. The lower level of pressure, on the other hand, maintains the patency of the airway during expiration increasing oxygen levels. Therefore, BIPAP can help improve the patient’s condition by decreasing the work of breathing, respiratory rate, and CO2 levels, and resting respiratory muscles. It can also increase oxygen levels and volume of every breath and correct blood PH by improving alveolar ventilation (Credland, 2013).
7. What is spirometry?
Spirometry is a means of assessing lung function that is the gold standard in the diagnosis and monitoring of COPD. It measures the volume of air expelled from the lungs after maximal inspiration. The values derived from this expiratory maneuver are matched to predicted normal values and the presence or absence of COPD confirmed as well as its severity. A diagnosis of COPD is made if the postbronchodilator FEV1 (forced expiratory volume) in 1 second /forced vital capacity ratio is <0.7 and FEV1 is < 80% of predicted. Spirometry detects the presence of airway obstruction and resistance in the small conducting airways, a feature of COPD that particularly affects expiration of airflow during expiration (Brashier and Kodgule, 2012; Currie, 2011).
8. Discuss the significance of the results by examining differences between Mr. Wenham’s spirometry and that of a normal individual?
The FEV1/FVC ratio of this patient is 0.5. The normal range of the FEV1/FVC ratio in normal patients is 0.7-0.8 although the lower value of 0.65-0.8 is considered acceptable in elderly adults. Values <0.7 indicate the presence of airflow obstruction. Therefore, the FEV1/FVC ratio of the patient shows that there is significant obstruction to airflow in the patient’s small airways. This is especially significant because these values were obtained after the patient had been managed for and improved following an acute exacerbation of COPD. The FEV1 of this patient is 0.75L. This value is lower than the 1.76-4.16L predicted value for a 70-year old male patient. The patient seems to be experiencing significant obstruction although determination of the severity of the patient’s disease is not possible as his height and race are not provided (Currie, 2011).
9. How does the pathology of COPD explain these differences?
In COPD patients, inflammation in the small airways causes hypersecretion of mucus, mucus impaction, and airway fibrotic remodeling. The inflammation reduces the caliber of the airway and increases airway resistance leading to reductions in airflow especially during expiration. This prolongs air removal from the lungs and is detected through spirometry as reductions in FEV1 after maximal inhalation. Patients with COPD experience FEV1 reductions of 50-60ml per year as compared to normal healthy individuals who experience losses of 20-30 ml (Brashier and Kodgule, 2012).
References
Brashier, B. B. and Kodgule, R., 2012. Risk factors and pathophysiology of chronic obstructive pulmonary disease. Supplement to JAPI, 60, p. 17-22.
Cazzola, M., Page, C. P., Calzetta, L. and Matera, M. G., 2012. Pharmacology and therapeutics of bronchodilators. Pharmacological Reviews, 64(3), pp. 450-504.
Credland, N., 2013. Non-invasive ventilation in COPD exacerbations. Nursing Times, 109, pp. 16-21.
Currie, G. P., 2011. ABC of COPD. West Sussex: Blackwell Publishing Ltd.
Jindal, S. K., 2008. Oxygen therapy: Important considerations. Indian J Chest Dis Allied Sci., 50, pp. 97-107.
MacNee, W., 2006. Pathology, pathogensis, and pathophysiology. BMJ, 332(7551), 1202-1204.
Rhoades, R. and Bell, D. R., 2009. Medical physiology: Principles for clinical medicine. Philadelphia: Lippincott Williams and Wilkins.
