Chronic Obstructive Pulmonary Disease - Essay Example

Running Head: Chronic Obstructive Pulmonary Disease Name Grade Course Tutor’s Name Case Study: Chronic Obstructive Pulmonary Disease (COPD) Pathophysiology template COPD is a heterogeneous process characterized by the presence of chronic bronchitis, and emphysema that leads to the development of airflow limitation that is partially reversible, progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases (GOLD, 2011 and Nicki, Walker & Stuart, 2010). Both chronic bronchitis and emphysema are usually regarded to be independent processes though they share common etiological factors and are often encountered together in the same patient. COPD is caused by long-term exposure to toxic particles and gases with cigarette smoking responsible for over 90% of cases (Nicki, Walker & Stuart, 2010). Also inhalation of smoke from biomass fuels in poorly ventilated areas, occupational exposure in coal miners and other indoor and outdoor pollution. Infections and poorly developed lungs predisposes to the development of emphysema (Kumar & Abbas, 2007). Genetic deficiency of antiprotease α1-antitrypsin, leads to increased tendency to develop emphysema that is enhanced by smoking and about 1% of all patients with emphysema have α1-Antitrypsin (α1AT) deficiency that can be either congenital or functional resulting from oxidative inactivation (Kumar & Abbas, 2007). Emphysema arises from two imbalances; the protease-antiprotease imbalance and oxidant-antioxidant imbalance which are summative in producing the end result of tissue damage (Kumar & Clark, 2007). The imbalance causes destructive effect from high protease activity in subjects with low antiprotease activity in genetic deficiency of the antiprotease α1-antitrypsin and development of emphysema. The inflammatory response is not entirely clear (Kumar & Clark, 2007), but chemoattractant effects of nicotine and the effects of reactive oxygen species contained in smoke activate inflammatory cells and enhance elastase activity in macrophages with production of cellular proteases resulting in tissue damage. Smoking also depletes these antioxidant mechanisms thereby inciting tissue damage. Clinical features include persistent productive cough with the production of sputum, wheeze and breathlessness. These may vary depending on the predominant condition (emphysema or chronic bronchitis) and the severity. Investigations: Pulmonary Function Tests, X-rays, Arterial Blood Gases, Hb levels, Sputum studies, α1-Antitrypsin levels, ECG and Echocardiogram as needed. Treatment- Bronchodilators such as β2 agonists, Anticholinergics, Corticosteroids and Antibiotics. Others are Oxygen (PRN) α1-Antitrypsin replacement (Kumar & Abbas, 2007) and managing complications Prevention- Smoking cessation, Vaccines (Influenza) Prognosis- COPD has variable course, stopping smoking improves the prognosis significantly (Nicki, Walker & Stuart, 2010), most patients die of respiratory failure with 50% of patients with severe breathlessness dying within 5 years (Kumar & Clark, 2007). Question 1 Mrs. White has smoked for more than 50 pack years contributing to her disease. Nicotine from tobacco smoke has direct chemoattractive effects and the reactive oxygen species in smoke plays a key role in the development of COPD. Activation of the transcription factor NF-κB leads encoding of TNF and chemokines (e.g. IL-8) that attract and activate neutrophils releasing their granules containing cellular proteases e.g. neutrophils elastase and cathepsin (Kumar & Clark, 2007). These proteases damage terminal respiratory units with the loss of alveolar-capillary bed and the supportive elastic connective tissue decreasing the elastic recoil and increasing lung compliance resulting in a premature expiratory airway collapse resulting in dyspnoea and obstructive symptoms.(Barnes, 2003) Smoking also perpetuates the oxidant-antioxidant imbalance leading to the development of oxidative damage. The free radicals in tobacco smoke deplete the antioxidant measures contributing to tissue damage. Mrs. White’s cough and increasing mucus production is induced by smoking. The irritant effects induce hypertrophy of mucous glands in the trachea and bronchi with a marked increase in mucin-secreting goblet cells. Also inflammation with infiltration of CD8+ T cells, macrophages, and neutrophils occur causing destruction and hence its coexistence with emphysema (Kumar & Clark, 2007). Loss of ciliated epithelium and irritation from smoke and inflammatory mediators account for the chronic cough. Microbial infection may have exacerbated Mrs. White’s condition as suggested by fever worsening the symptoms. Diaphragmatic movements account for 75% of the change in intrathoracic volume (Ganong, 2003) during normal breathing but when pathology ensues as in Mrs. White’s case, use of accessory muscles of respiration such as scalene and sternocleidomastoid muscles occur to maintain adequate ventilation. This results from detection of changes in blood gases majorly PCO2 by central respiratory control centre in the medulla that recruits accessory muscles. The anxiety can be due to the central response to rising levels of PCO2. Blood Gas analysis features such as low pH is due to CO2 retention, low PaO2 and increased PaCO2 due to airflow limitation and increased HCO3 levels are due to compensatory mechanisms to maintain a normal pH. The reduction in flow rates result from the destructive effects causing a loss of elastic recoil in the support tissue of the airways causing an increased dynamic airway compression worse on forced expiration. The expiratory time prolongation with premature airway closure caused by loss of elastic recoil, and the resulting air trapping resulting in increased RV and FRC subsequently increasing TLC (Scalm et al., 2000). The X-ray findings showing a flattened diaphragm and lung hyperinflation with increased AP diameter of the chest is due to obstructive process and air retention. Question 2: Progressive hypertrophy and hyperplasia of the mucus-secreting goblet cells of the bronchial tree occurring due to irritation result in progressive mucus hypersecretion as in Mrs. White’s case. The inflammatory process from the infiltration of the walls of the bronchi and bronchioles with acute and chronic inflammatory cells that occur promotes the above structural changes and may cause scarring and remodeling process that thickens the walls and leads to widespread narrowing in the small airways leading to dyspnoea (Kumar & Clark, 2007). Cough is a protective reflex in response to noxious stimuli. Tobacco smoke and its contents are irritating to the airway and damage the normal epithelium exposing nerve endings and allowing foreign particles to reach terminal airway hence triggering the cough reflex. Central cyanosis results from the reduced arterial oxygen saturation and is usually caused by cardiac or pulmonary disease (Swash & Glyn, 2007). In Mrs. White’s situation it is due to poor ventilation from COPD causing a higher concentration of deoxygenated hemoglobin. With long standing disease cardiac complication (Cor Pulmonale) sets in due to pulmonary hypertension (Kumar & Clark, 2007) and may explain her blood pressure(140/90mmHg). Dyspnoea is worse on exertion due increased demands for oxygen that cannot be met by her present physiological state as most of ventilator reserve is exhausted. She has tachypnoea which is meant to aid oxygen delivery and is due to central stimulus (Ganong, 2003). Her decreased breath sounds on auscultation is due to obstruction limiting airflow and hyperinflation that restricts diaphragm movement. She is febrile indicating an underlying infection. Question 3: Salbutamol is a sympathomimetic agent acting on β2 receptors causing relaxation of airway smooth muscle hence bronchodilation. Action β2 receptor also relaxes airway smooth muscle, and inhibits inflammatory mediator release. The obstruction due to acute bronchospasms and structural changes from destruction is relieved by Salbutamol and also muscarinic responses are relieved by physiological antagonism of Salbutamol. This is very useful especially during acute exacerbations due to acute reliever effects of Salbutamol and bronchodilation is maximal within 15–30 minutes and persists for 3–4 hours (Betram, 2007).Many patients feel better following the inhalation of a β adrenergic agonist and objectively have an improved peak flow rates (Kumar & Clark, 2007). Prednisolone a corticosteroid that reduces bronchial reactivity and airway obstruction through their contraction of engorged mucosal vessels and their potentiating effects on β2 receptor agonists. Prednisolone given orally daily for 2 weeks with pulmonary function tests is associated with is objective evidence of a substantial improvement in airflow limitation (FEV1 increase > 15%), (Kumar & Clark, 2007) and this is replaced by inhaled corticosteroids adjusted according to patients response. It inhibits the concentration, distribution, and function of peripheral leukocytes with suppression of the inflammatory cytokines and chemokines other inflammatory mediators (Betram, 2007) reducing airway remodeling. References Barnes, P.J. (2003). New concepts in chronic obstructive pulmonary disease. Annu Rev Med; 54:113. [PMID: 12359824] Betram, G. K. (ED 10). (2007). Basic & Clinical Pharmacology. New York: McGraw-Hill. Fauci & Braunwald. et al. (Ed 17). (2008). Harrison’s PRINCIPLES OF INTERNAL MEDICINE. New York: McGraw Hill, USA. Ganong, F. W. (Ed 21). (2003). Review of Medical Physiology. New York: McGraw-Hill. Global Initiative for Obstructive Lung Disease (GOLD). (December, 2011). Retrieved from < http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html> Kumar & Abbas. (2007). Robbins Basic Pathology. Saunders. Elsevier Health Sciences. Kumar, P. & Clark, M. (6th Ed). (2007).Clinical medicine. Saunders: Elsevier Health Sciences. Nicki, R., Walker, R. & Stuart, H. (ED 21). (2010). Davidson's Principles and Practice of Medicine: Principles & Practice of Medicine. Saunders: Elsevier Health Sciences. Scalm P. D. et al. (2000). Am Resp Crit Centre Med 161:381-390 Swash, M. & Glyn, M. (2007). Hutchison’s Clinical Methods: An Integrated approach to Clinical Practice. Saunders: Elsevier Health Sciences. Read More