25-Year-Old Woman With Increasing Abdominal Girth and Shortness of Breath

Abstract

A 25-year-old woman presented to her local emergency department with symptoms of increasing abdominal girth and shortness of breath during the previous week. Her clothes no longer fit at her waist and she had gained 4.5 kg within the past week. In addition to feeling bloated, the patient had abdominal pain, nausea, and subjective fevers. The pain in her abdomen and back, which she rated as an 8 on a 10-point scale, became worse with movement. She had a complicated medical history, having been diagnosed as having neuroblastoma at the age of 6 months. She had been treated with a laminectomy of several thoracic vertebrae, chemotherapy, and radiation. She had resultant kyphoscoliosis, T4 paraplegia, and asymptomatic chronic hypoxia with a baseline hemoglobin saturation of around 80%. Alcohol use consisted of 12 to 16 drinks per week up until 1 year previously, with only minimal alcohol use since that time. She did not use tobacco or recreational drugs. On physical examination, the patient had severe kyphoscoliosis with a scoliotic angle of 116ϒ and T4 paraplegia. Cardiac examination revealed a grade 2/6 systolic murmur at the base with a faint diastolic component and a prominent pulmonic valve component (P2). Lung examination was difficult secondary to her anatomy, but no wheezes or rhonchi were auscultated bilaterally. Her abdomen was distended with shifting dullness and was nontender. She had pitting edema of both legs to the level of her knees. Her vital signs were as follows: respiratory rate, 20 breaths/min; hemoglobin saturation, 80% on blow by face mask supplemental oxygenation; heart rate, 86 beats/min; blood pressure, 99/58 mm Hg; and no fever. Laboratory studies yielded the following results (reference ranges shown parenthetically): B-type natriuretic peptide level, 606 pg/mL (<64 pg/mL); bicarbonate level, 35 mmol/L (22-29 mmol/L); and normal white blood cell and platelet counts and hemoglobin, sodium, potassium, and creatinine levels. An arterial blood gas study revealed a pH of 7.39 (7.35-7.45), a Po2 of 41 torr (70-100 torr), and a Pco2 of 54 torr (35-45 torr). Urinalysis showed nitrates with 3+ proteins, 1+ bilirubin, and a negative Gram stain. Computed tomography (CT) of the chest, abdomen, and pelvis performed at the local hospital revealed ascites with small bilateral pleural effusions, a small pericardial effusion, and normal spleen size, with no hepatic masses or bile duct dilatation. The patient was subsequently transferred to Saint Marys Hospital emergency department. 1.Which one of the following tests would provide the greatest amount of diagnostic information for this patient at this time? a.Measurement of hepatic enzyme activityb.24-hour urine protein collectionc.Urine pregnancy testd.Abdominal paracentesise.Liver ultrasonography The patient has ascites, as evidenced by findings on physical examination and CT. Measurement of hepatic enzyme activity might help show any liver abnormalities that could be causing the ascites; however, the differential diagnosis of ascites is wide and not limited to hepatic etiologies. These tests are reasonable with the patient's history of alcohol use but would not give the greatest diagnostic yield. A 24-hour urine protein collection again may be reasonable with the patient's 3+ protein on urinalysis but only allows the physician to evaluate a renal cause of ascites. A urine pregnancy test is reasonable in a woman of childbearing age, especially before any medication or diagnostic imaging modality is used that could be harmful to a fetus. In this patient, a urine pregnancy test is needed but would not give the greatest diagnostic yield because her physical examination and CT findings show ascites to be the cause of her increasing abdominal girth. An abdominal paracentesis would give the greatest diagnostic yield because it provides a variety of information. The color of the ascitic fluid, presence and types of cells, and the serum-to-ascites albumin gradient (SAAG) can help to narrow the differential diagnosis. The presence of a SAAG greater than or equal to 1.1 g/dL suggests portal hypertension as an underlying etiology, whereas a lower SAAG suggests other causes of ascites.1McHutchison JG Differential diagnosis of ascites.Semin Liver Dis. 1997; 17: 191-202Crossref PubMed Scopus (47) Google Scholar In addition, the total number of nucleated cells is diagnostic of spontaneous bacterial peritonitis, a potentially life-threatening condition that warrants expedient antibiotic therapy. Bacteria are only detectable in 42% to 65% of ascitic fluid cultures because of laboratory techniques, small volume cultures, and low bacterial concentrations in the fluid2Runyon BA Canawati HN Akriviadis EA Optimization of ascitic fluid culture technique.Gastroenterology. 1988; 95: 1351-1355PubMed Google Scholar; however, if findings on culture are positive, therapy can be assessed with antimicrobial susceptibilities. Finally, ultrasonography of the liver is an excellent test for visualizing liver masses or parenchymal changes but only looks at 1 potential cause of ascites. Furthermore, the liver parenchyma was noted to be normal on CT. An abdominal paracentesis was completed on admission and yielded 370 mL of serous fluid with 100 total nucleated cells/∞L, a glucose level of 71 mg/dL, a total protein level of 2.4 g/dL, and a SAAG of 1.3 g/dL. The patient's dyspnea and abdominal pain improved after the removal of the fluid. 2.Which one of the following studies would be most useful for confirming the etiology of the ascites? a.Liver ultrasonography with Doppler imagesb.Echocardiographyc.Liver biopsyd.24-hour urine protein collectione.Measurement of pancreatic enzyme activity The high SAAG of greater than 1.1 g/dL suggests a diagnosis of portal hypertension with many possible underlying etiologies, including cirrhosis, heart failure, Budd-Chiari syndrome, portopulmonary hypertension, and alcoholic hepatitis.1McHutchison JG Differential diagnosis of ascites.Semin Liver Dis. 1997; 17: 191-202Crossref PubMed Scopus (47) Google Scholar Ultrasonography of the liver with Doppler imaging would determine flow in the hepatic vein for evaluation of Budd-Chiari syndrome or thrombosis, which is possible but unlikely in this patient's scenario. Echocardiography is a noninvasive means of confirming a cardiac etiology of ascites, which seems most likely in this patient given the murmur, prominent P2 on physical examination, and elevated B-type natriuretic peptide levels. Liver biopsy could be considered if other diagnostic testing is unrevealing, but it would not be the test of choice at this juncture given the otherwise normal liver parenchyma on CT (no evidence of masses or parenchymal lesions). Renal and pancreatic causes for ascites are more often seen when the SAAG is less than 1.1 g/dL. Thus, urine protein collection and measurement of pancreatic enzyme activity are not likely to confirm the diagnosis in this patient who has an elevated SAAG. Transthoracic echocardiography revealed a left ventricular ejection fraction of 74%, a moderate to severe decrease in right ventricular function, severe right ventricular enlargement, a dilated inferior vena cava, right atrial enlargement compressing the left atrium, normal left atria, mild aortic and mitral valve regurgitation, moderate to severe tricuspid valve regurgitation, and an estimated right ventricular systolic pressure of 112 mm Hg in the setting of a systolic blood pressure of 99 mm Hg. Cardiac output was 3.69 L/min. Bedside pulmonary function testing revealed a forced vital capacity of 0.43 L (15% of predicted), a forced expiratory volume in 1 second of 0.36 L/s (14% of predicted), and a forced expiratory volume in 1 second to forced vital capacity ratio of 83.72%. 3.Which one of the following is the most likely cause of this patient's condition? a.Chronic pulmonary thromboembolic diseaseb.Chronic hypoxemiac.Idiopathic pulmonary hypertension (PH)d.Left ventricular dysfunctione.Valvular disease The echocardiographic findings suggest a diagnosis of PH. All the choices are potential causes of PH. Chronic pulmonary thromboembolic disease is a reasonable choice because of the patient's limited mobility. However, CT revealed no evidence of acute or chronic thromboembolic disease. Chronic hypoxemia is the most likely cause of the patient's PH given her low baseline oxygen saturation and pulmonary restriction with no evidence of underlying cardiac structural abnormalities revealed on echocardiography. Idiopathic PH is a diagnosis of exclusion, usually given when no other etiology is suggested by cardiac and pulmonary testing; such was not the case in our patient. Echocardiography revealed a normal left ventricular ejection fraction, making left ventricular dysfunction unlikely, and provided no evidence of substantial valvular disease. 4.On the basis of the classification of PH by the World Health Organization (WHO), into which one of the following groups would this patient's condition be categorized? a.Group 1b.Group 2c.Group 3d.Group 4e.Group 5 The WHO last updated the classification of PH in 2003. This classification scheme divides PH into 5 distinct categories on the basis of pathophysiology and symptom presentation. Group 1 is classified as pulmonary arterial hypertension (PAH) and contains idiopathic and familial etiologies as well as PAH caused by conditions of the thyroid, connective tissue, human immunodeficiency virus, and drugs. The remaining 4 groups are defined as PH. Group 2 is classified by left-sided heart disease. Group 3 PH is caused by chronic lung disease and hypoxemia, as was the case in our patient. Group 4 is defined as PH caused by chronic thromboembolic lung disease, and the last category, group 5, contains miscellaneous causes for PH, including sarcoidosis, histiocytosis X, and mass effect on the pulmonary vasculature.3Simonneau G Galiè N Rubin LJ et al.Clinical classification of pulmonary hypertension.J Am Coll Cardiol. 2004; 43: 5S-12SAbstract Full Text Full Text PDF PubMed Scopus (1549) Google Scholar The patient was seen in consultation by both pulmonary and pulmonary hypertension specialists who recommended positive pressure ventilation at night to assist with ventilatory support, continuous supplemental oxygen, and a right heart catheterization to assess her response to nitric oxide, confirm the diagnosis, and assess pressures. 5.Which one of the following is the goal of a nitric oxide trial in this patient? a.Assess for a change in pulmonary arterial pressureb.Assess for a change in systemic systolic blood pressured.Assess for a change in cardiac outpute.Determine if continuous medication infusion is appropriatef.Determine if anticoagulation is appropriate By assessing for a change in pulmonary arterial pressure, the nitric oxide test is used not only to help with the diagnosis of PH but also as a guide to which therapies will be tolerated by each patient. During the test, a patient is noted to be a responder if the mean pulmonary arterial pressure decreases by more than 10 mm Hg or decreases below 40 mm Hg. Such a response would suggest therapeutic benefits of a calcium channel blocker or other vasodilator. However, less than 15% of patients are deemed “responders” by this definition.4De Marco T Pulmonary arterial hypertension and women.Cardiol Rev. 2006; 14: 312-318Crossref PubMed Scopus (8) Google Scholar Although changes in systemic blood pressure and cardiac output may be seen with nitric oxide, these are not the primary variables assessed in nitric oxide testing. A continuous infusion of a medication such as epoprostenol may be a therapeutic option; however, several other variables must be considered before starting a continuous infusion.4De Marco T Pulmonary arterial hypertension and women.Cardiol Rev. 2006; 14: 312-318Crossref PubMed Scopus (8) Google Scholar Chest CT with contrast agent can determine whether a pulmonary embolus is present and whether anticoagulation should be considered. A right heart catheterization was attempted, but the patient developed respiratory depression and severe hypoxemia during the procedure because of prolonged recumbency, perhaps exacerbated by medications given for anxiety and back pain. Because of the patient's discomfort and inability to lie flat on her back, no further attempts at catheterization were made. A trial of nitric oxide was done noninvasively, and the patient's blood pressure remained stable; she had no adverse effects from the medication. The patient was prescribed sildenafil before being discharged, and her abdominal pain and shortness of breath improved. She was discharged with home oxygen and bilevel positive airway pressure, and follow-up appointments were scheduled with the pulmonary hypertension specialists as well as her primary care physician. Our patient was unusual in that she had severe kyphoscoliosis, present from a young age, and had resultant PH from chronic hypoxemia. Scoliosis is a curvature of the spine typically defined as being greater than 10ϒ on a chest radiograph using the Cobb method of angle calculation.5Kane WJ Scoliosis prevalence: a call for a statement of terms.Clin Orthop Relat Res. 1977 Jul-Aug; : 43-46PubMed Google Scholar The prevalence of scoliotic angles greater than 70% (which would include our patient) is 0.1 per 1000.6Bergofsky EH Respiratory failure in disorders of the thoracic cage.Am Rev Respir Dis. 1979; 119: 643-669PubMed Google Scholar Scoliosis and the association with restrictive lung disease are well documented. The Pao2, alveolar ventilation, and tidal volume were shown in earlier studies to be inversely related to the scoliotic angle.7Kafer ER Idiopathic scoliosis: gas exchange and the age dependence of arterial blood gases.J Clin Invest. 1976; 58: 825-833Crossref PubMed Scopus (32) Google Scholar Recent studies have confirmed that lung function becomes more impaired as the angle of scoliosis increases. Also, an apex of scoliosis at a spinal level higher than T10 has been associated with poorer respiratory function.8McMaster MJ Glasby MA Singh H Cunningham S Lung function in congenital kyphosis and kyphoscoliosis.J Spinal Disord Tech. 2007; 20: 203-208Crossref PubMed Scopus (46) Google Scholar Thus, the changes in ventilation seen with severe scoliotic angles may lead to chronic hypoxia and PH in some persons. Pulmonary hypertension is a complex and life-threatening disease characterized by elevated pulmonary arterial pressures. It is defined as a mean pulmonary arterial pressure of greater than 25 mm Hg at rest. This typically corresponds to a pulmonary arterial systolic pressure of greater than 35 to 40 mm Hg with exercise by Doppler echocardiography. The criterion standard of diagnosis remains right heart catheterization and is defined as a mean pulmonary arterial pressure of greater than 25 mm Hg at rest or greater than 30 mm Hg with exercise.9Barst RJ McGoon M Torbicki A et al.Diagnosis and differential assessment of pulmonary arterial hypertension.J Am Coll Cardiol. 2004; 43: 40S-47SAbstract Full Text Full Text PDF PubMed Scopus (832) Google Scholar The pathogenesis of PH and PAH is complex, stemming from their many etiologies; studies are ongoing to further elucidate these processes. Chronic hypoxia was thought to be the mechanism in our patient. Rat models have shown that chronic hypoxia causes lung injury and remodeling of the pulmonary vasculature, such as extension of the musculature into smaller arteries, thickening of the medial arterial musculature, and loss of smaller vessels in the lungs.10Rabinovitch M Gamble W Nadas AS Miettinen OS Reid L Rat pulmonary circulation after chronic hypoxia: hemodynamic and structural features.Am J Physiol. 1979; 236: H818-H827PubMed Google Scholar These changes lead to the abnormal flow and increased pulmonary vascular resistance. The prognosis in patients with PH varies by WHO classification and has not been well studied. One study surveyed mortality and hospitalizations due to PH in patients in the United States from 1980 to 2002. During this time period, the annual number of deaths from all causes of PH was estimated to be between 10,219 and 15,668. Mortality rates varied per year from 4.7 to 5.5 per 100,000. Mortality rates showed an increasing trend throughout the study years.11Hyduk A Croft JB Ayala C Zheng K Zheng ZJ Mensah GA Pulmonary hypertension surveillance—United States, 1980-2002.MMWR Surveill Summ. 2005; 54: 1-28PubMed Google Scholar Common presenting symptoms and signs suggestive of PH include dyspnea, lower extremity edema, fatigue, weakness, syncope, and angina in advanced disease.12Rich S Dantzker DR Ayres SM et al.Primary pulmonary hypertension: a national prospective study.Ann Intern Med. 1987; 107: 216-223Crossref PubMed Scopus (1739) Google Scholar Pulmonary hypertension may be asymptomatic; however, in its early stages it can be an incidental finding on echocardiography. Physical examination commonly reveals a loud P2. This finding was reported in 93% of participants in one study.12Rich S Dantzker DR Ayres SM et al.Primary pulmonary hypertension: a national prospective study.Ann Intern Med. 1987; 107: 216-223Crossref PubMed Scopus (1739) Google Scholar Other findings commonly heard are a third heart sound (S3), fourth heart sound (S4), and murmurs consistent with tricuspid regurgitation and pulmonic insufficiency. Cyanosis and lower extremity edema were seen in 20% and 32% of patients, respectively.12Rich S Dantzker DR Ayres SM et al.Primary pulmonary hypertension: a national prospective study.Ann Intern Med. 1987; 107: 216-223Crossref PubMed Scopus (1739) Google Scholar The evidence-based clinical practice guidelines of the American College of Chest Physicians suggest that, if the patient's history and physical examination give clues that point toward a diagnosis of PH, electrocardiography to evaluate for other cardiac diseases and chest radiography should be performed. The recommendations further suggest Doppler echocardiography as a noninvasive screening tool because it can estimate pulmonary pressures, evaluate right and left ventricular systolic function and size, and assess for structural abnormalities, including valvular disease and chamber enlargement.13McGoon M Gutterman D Steen V et al.Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines.Chest. 2004; 126: 14S-34SCrossref PubMed Scopus (733) Google Scholar Once the diagnosis of PH is suggested by echocardiography, further studies to elucidate the underlying etiology should be performed, such as testing for human immunodeficiency virus or work-up for thromboembolic and connective tissue disease. If a pulmonary etiology is suspected in PH, as in the case of our patient, pulmonary function and arterial blood gas oxygenation testing should be done to evaluate the extent of lung disease. Right heart catheterization, which should be performed to confirm the diagnosis in patients with PH of suspected pulmonary etiology, can help determine the extent of disease, determine medical management, and give insight on prognosis.13McGoon M Gutterman D Steen V et al.Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines.Chest. 2004; 126: 14S-34SCrossref PubMed Scopus (733) Google Scholar Treatment of PH differs slightly by classification. In group 3 patients, the hallmarks of therapy are continuous supplemental oxygen and pressure support ventilation at night. Pulmonary vascular-specific therapies have not been proven useful in group 3 patients. Patients with other classes of PH have been shown to respond to various pharmacotherapies, including therapies with prostanoids, calcium channel blockers, endothelin receptor antagonists, and phosphodiesterase inhibitors. Various surgical options including transplant are also available. The goal of therapy for PH is not cure but rather the attainment of the highest activity level possible by the patient. Overall, PH is a life-threatening disease with many causes. Early recognition of the signs and symptoms of disease in persons at risk of developing PH are important. Once PH has been recognized, the underlying cause should be sought expeditiously. Timely detection and recognition should be stressed because they may affect treatment choices and prognosis.