Sample Paper: Pathology Report: Bronchopulmonary Dysplasia
Introduction to the Pathology
Bronchopulmonary dysplasia (BPD) is an illness that affects the lungs of newborns. The disease has higher prevalence rates in premature newborns. BPD affects how the breathing of newborns, making them require oxygen therapy. The oxygen is given through a breathing tube, a mask, and nasal prongs (National Heart, Lung, and Blood Institute, n.d.). Proper gas exchange occurs when there is an increased lung surface area with an expanded number of blood vessels, an increased number of alveoli, and a thin alveolar-capillary barrier. The surface area of the lung increases at the later stages of lung development. These are the saccular and alveolar stages. This stage of lung development is interrupted in patients with BPD. This then leads to an ineffective respiratory system that cannot achieve gas exchange. Respiratory support is therefore needed to enable gas exchange. Advances in neonatal and perinatal care of preterm infants have changed the pathology of BPD. Treatments such as gentle ventilation, postnatal surfactant, and antenatal steroids have changed how BPD affects infants. The classic pathology of BPD was characterized by hypertensive remodeling of the pulmonary arteries, extensive alveolar septal fibrosis marked airway smooth muscle hyperplasia, and squamous metaplasia. The new pathology is characterized by mild airway smooth muscle thickening, reduced dysmorphic vascular bed with rare epithelial lesions, and a simplified alveolar structure (Thekkeveedu, Guaman & Shivanna, 2017).
Etiology of the Pathology
Antenatal factors contribute to the disease. These factors include genetic susceptibility. Twin studies demonstrate that genetics contribute to BPD. The occurrence of moderate to severe BPD is higher in identical twins as compared with non-identical twins. Candidate genes that contribute to the BPD have also been identified using a genome-wide association study. Population-based studies, however, do not demonstrate the relationship between genomic loci with moderate to severe BPD. These findings demonstrate that BPD is caused by multiple genes and pathways. Intrauterine growth restriction (IUGR) also contributes to the disease. It is hypothesized that biological mechanisms that lead to IUGR can also contribute to restricted fetal lung growth. These factors include vascular endothelial growth factor (VEGF), VEGF receptor and placental dysfunction, and deficiency of insulin growth factor. Chorioamnionitis also contributes to BPD. This condition occurs due to the inflammation of the membranes that surround the fetus (amnion and chorion) due to a bacterial infection. Pregnancy-induced hypertensive disorders also contribute to the condition. Pregnancy-induced hypertensive disorders include eclampsia, preeclampsia, and gestational hypertension. These disorders cause an imbalance between pro and anti-angiogenetic mediators, which then leads to decreased angiogenesis. This then interrupts lung development. Maternal smoking also contributes to the condition. Studies have consistently demonstrated that maternal smoking increases the incidence of preterm birth and complications related to preterm birth, such as BPD. Cigarette smoke disrupts normal lung development and function through dysregulated angiogenesis, altered alveolar type II cell metabolism, placental dysfunction, and epigenetic changes (Thekkeveedu, Guaman & Shivanna, 2017).
Natal factors also contribute to BPD. These factors include premature birth and low birth weight, which are the strongest risk factors for BPD. Preterm birth contributes to BPD due to functional immaturity. It also contributes to the disease due to routine life-saving interventions such as mechanical ventilation and oxygen supplementation that are used on preterm birth infants. These interventions injure the lungs and may interrupt lung development (Thekkeveedu, Guaman & Shivanna, 2017).
Postnatal factors also contribute to the condition. These factors include oxidative stress and hyperoxia. The risk of oxidative stress is high in premature infants due to exposure to free iron, increased susceptibility to infection and inflammation, and immature antioxidant defenses. Oxidative stress then causes a disruption of lung development. The mechanisms that take place during the interrupted lung development are vasculogenesis, apoptosis, cell proliferation extracellular matrix assembly, and disruption of growth factor signaling. Another contributor to BPD is sepsis. Studies show an increased risk of BPD in postnatal sepsis. Sepsis affects lung development by causing endothelial injury in the lungs, oxidative stress, and inflammation. Patent ductus arteriosus (PDA) also contributes to BPD. The ductus arteriosus is usually present in fetuses where it shunts blood from the pulmonary artery to the aorta so as to avoid the high resistance of the non-functioning lungs. The ductus arteriosus closes a few days of birth; however, in some patients, the ductus arteriosus does not close leading to PDA. PDA is common in low birth weight patients and worsens lung injury. Respiratory microbial dysbiosis also contributes to BPD. Dysbiosis refers to an imbalance of the complex microbial communities inside the body or on the body. The microbial colonization of the human respiratory tract starts in utero or shortly after birth. Bacterial diversity can be decreased by bowel colonization, method of feeding, mode of delivery, antibiotic exposure, chorioamnionitis. These changes increase the microbial colonization in the lungs, which may then lead to inflammatory lung phenotype, which then plays a key role to the development of BPD (Thekkeveedu, Guaman & Shivanna, 2017).
The signs of BPD include premature newborns requiring oxygen therapy after reaching 36 weeks of gestation. Another sign is feeding problems. This leads to delayed growth. Another sign is pulmonary hypertension which is caused by increased pressure in the pulmonary artery. Cor palmonale also occurs in patients with BPD. This condition is characterized by failure in the right-hand side of the heart. This condition occurs when the blood pressure on the pulmonary artery and the lower right chamber of the heart is high (National Heart, Lung, and Blood Institute, n.d.).
The diagnostic procedures include the evaluation of the blood gas. The condition affects the breathing of the patient, and blood gas can reveal the existence of the disease. The examination of blood gas may reveal acidosis, hypercarbia, and hypoxia, all of which demonstrate BPD. The diagnosis also involves chest radiographs. This test shows decreased lung volumes, pulmonary interstitial emphysema, pulmonary edema, area of atelectasis, and hyperinflation. Diagnosis also involves using an echocardiogram. This device is used to examine pulmonary hypertension. The diagnosis of the disease done using postmenstrual age. Oxygen requirement at 36 weeks postmenstrual age signifies BPD. Differential diagnoses that should be examined include pulmonary interstitial emphysema, tracheomalacia, pulmonary hypertension, pneumonia, and pulmonary atelectasis (Sahni & Mowes, 2020).
Treatment strategies include preventing the development of BPD. This includes prenatal prevention. Prenatal prevention focuses on preventing premature birth. This happens by surgical closure of the cervix with cerclage, maternal progesterone supplementation, reducing the risk of multiple pregnancies by avoiding fertility treatment when several follicles are potentially available for ovulation, and encouraging pregnant women to avoid smoking.
Postnatal prevention involves ventilation. Avoiding lung overinflation and high tidal volumes is essential. This can be achieved by permissive hypercapnia with a partial pressure of carbon dioxide in the arterial blood (PaCO2) from 45 mmHg to 55 mmHg and a pH greater than 7.20. Intubation should also be reduced as much as possible. Non-invasive respiratory ventilation procedures are also encouraged. They include high flow nasal cannulas (HFNCs), nasal continuous positive airway pressure (NCPAP), and non-invasive positive pressure ventilation (NIPPV). Another preventive strategy is oxygen supplementation. In the first few minutes of life, the SpO2 should be 70% to 80%. After 5 minutes, the SpO2 should be maintained from 88% to 92%, with an alarm limit of 96%. The preventive treatments also include surfactant administration. Surfactant reduces preterm mortality and can be used to modify the mechanisms that contribute to BPD. Another preventive treatment is glucocorticosteroid administration. This reduces the risk of BPD in ventilated preterm patients. Caffeine is also a preventive treatment strategy. Caffeine reduces the risk of BPD development. This could happen due to the anti-inflammatory properties of caffeine which may reduce the pathogenic mechanisms of BPD. Vitamin A treatment can also be used to prevent the development of BPD. Vitamin A is important to the integrity and development of the respiratory tract. The supplementation of vitamin A might therefore reduce the risk of BPD. Nitric oxide is also a treatment to prevent the development of BPD. It has been found effective in treating term neonates with persistent pulmonary hypertension and hypoxemic respiratory failure. Another treatment is cell therapy. Exogenous stem or progenitor cells can be used to regenerate or protect a damaged lung (Principi, Di Pietro & Esposito, 2018).