The Journal of Emergency Medicine Vol 5, pp 415-419, 1987 PrInted in the USA ?? CopyrIght 8~’ 1987 Pergamon Journals Ltd PERIPHERAL EDEMA AND CHEST PAIN IN A YOUNG MALE ?? Dr Kenneth V. Iserson: Today we will discuss the case of a patient presenting to the emergency department with pleuritic chest pain and peripheral edema. The dis- cussant will be Steven M. Chernow, MD, of the Section of Emergency Medicine, Uni- versity of Arizona College of Medicine. An 18-year-old man presented to the emergency department with two days of left pleuritic chest pain. The pain was de- scribed as sharp, persistent, nonradiating, and mildly relieved by leaning forward. He denied fever, chills, cough, shortness of breath, or upper respiratory symptoms. Three weeks prior to his emergency de- partment visit, the patient noted swelling of both lower extremities. The patient had a 3-year history of hypertension treated with hydrochlorothiazide/triamterene (DyazideTM). He smoked one pack of ciga- rettes per day and denied using alcohol or drugs. Family history and review of sys- tems were unremarkable. On physical examination in the emer- gency department, the patient appeared well nourished and in no acute distress. His vital signs were as follows: tempera- ture, 99°F; blood pressure, 125/90 mm Hg; pulse rate, 95 beats per minute; and respirations, 20/min. Head and neck ex- amination findings were unremarkable. His chest was clear to auscultation and percussion. Cardiac exam revealed a nor- mal first and second heart sound without gallops, rubs, clicks, or murmurs. Pulses were present and symmetric. His abdo- men was soft with normal bowel sounds and no organomegaly. Bilateral pitting edema of both lower extremities was not- ed. Rectal examination findings were nor- mal and there were no neurologic deficits. Initial laboratory studies included the following: WBC 6,OOO/pL with a normal differential; hemoglobin, 12.7 g/dL; sodi- um, 137 mmol/L; potassium, 3.8 mmol/ L; chloride, 100 mmol/L; bicarbonate, 29 mmol/L; BUN, 16 mg/dL; creatinine, 1.3 mg/dL; and glucose, 102 mg/dL. Urinal- ysis revealed a specific gravity of 1.021, pH of 6.0, 4+ protein, negative for glu- cose, 0 to 2 RBCs, 15 to 20 WBCs, 2 to 4 hylaine casts, and refractile lipid bodies consistent with lipiduria. A room air blood gas determination revealed a pH of 7.43, pC0, of 35 torr, and p0, of 98 torr. The chest x-ray study was normal. An ECG was normal except for what was in- terpreted as J-point elevation. An echo- cardiogram demonstrated no evidence for a pericardial effusion. A ventilation-per- fusion scan yielded a large segmental mis- matched defect. The patient was admitted with a diag- nosis of pulmonary embolus and possible nephrotic syndrome. Heparin therapy was initiated. Further laboratory studies in- Emergency Case Records originates from case conferences held at Denver General Hospital’s Department of Emergency Medical Services and is coordinated by Michael Brunko, MD. RECEIVED: 24 November 1986; ACCEPTED: 3 February 1987 0736-4679/87 $3.00 + .OO 415
Transcript
The Journal of Emergency Medicine Vol 5, pp 415-419, 1987 PrInted in the USA ?? CopyrIght 8~’ 1987 Pergamon Journals Ltd
PERIPHERAL EDEMA AND CHEST PAIN IN A YOUNG MALE
??Dr Kenneth V. Iserson: Today we will discuss the case of a patient presenting to the emergency department with pleuritic chest pain and peripheral edema. The dis- cussant will be Steven M. Chernow, MD, of the Section of Emergency Medicine, Uni- versity of Arizona College of Medicine.
An 18-year-old man presented to the emergency department with two days of left pleuritic chest pain. The pain was de- scribed as sharp, persistent, nonradiating, and mildly relieved by leaning forward. He denied fever, chills, cough, shortness of breath, or upper respiratory symptoms.
Three weeks prior to his emergency de- partment visit, the patient noted swelling of both lower extremities. The patient had a 3-year history of hypertension treated with hydrochlorothiazide/triamterene (DyazideTM). He smoked one pack of ciga- rettes per day and denied using alcohol or drugs. Family history and review of sys- tems were unremarkable.
On physical examination in the emer- gency department, the patient appeared well nourished and in no acute distress. His vital signs were as follows: tempera- ture, 99°F; blood pressure, 125/90 mm Hg; pulse rate, 95 beats per minute; and respirations, 20/min. Head and neck ex- amination findings were unremarkable. His chest was clear to auscultation and percussion. Cardiac exam revealed a nor-
mal first and second heart sound without gallops, rubs, clicks, or murmurs. Pulses were present and symmetric. His abdo- men was soft with normal bowel sounds and no organomegaly. Bilateral pitting edema of both lower extremities was not- ed. Rectal examination findings were nor- mal and there were no neurologic deficits.
Initial laboratory studies included the following: WBC 6,OOO/pL with a normal differential; hemoglobin, 12.7 g/dL; sodi- um, 137 mmol/L; potassium, 3.8 mmol/ L; chloride, 100 mmol/L; bicarbonate, 29 mmol/L; BUN, 16 mg/dL; creatinine, 1.3 mg/dL; and glucose, 102 mg/dL. Urinal- ysis revealed a specific gravity of 1.021, pH of 6.0, 4+ protein, negative for glu- cose, 0 to 2 RBCs, 15 to 20 WBCs, 2 to 4 hylaine casts, and refractile lipid bodies consistent with lipiduria. A room air blood gas determination revealed a pH of 7.43, pC0, of 35 torr, and p0, of 98 torr. The chest x-ray study was normal. An ECG was normal except for what was in- terpreted as J-point elevation. An echo- cardiogram demonstrated no evidence for a pericardial effusion. A ventilation-per- fusion scan yielded a large segmental mis- matched defect.
The patient was admitted with a diag- nosis of pulmonary embolus and possible nephrotic syndrome. Heparin therapy was initiated. Further laboratory studies in-
Emergency Case Records originates from case conferences held at Denver General Hospital’s Department of Emergency Medical Services and is coordinated by Michael Brunko, MD.
RECEIVED: 24 November 1986; ACCEPTED: 3 February 1987 0736-4679/87 $3.00 + .OO
415
416 Steven M. Chernow and Kenneth V. lserson
eluded normal liver enzymes, a total pro- tein of 4.2 g/dL, albumin of 1.4 g/dL, cholesterol of 549 mg/dL, normal com- plement levels, negative antinuclear anti- bodies, nonreactive VDRL, and a nega- tive hepatitis B surface antigen. A 24-hour urine contained 11.4 g of protein with a creatinine clearance of 150 mL/min. A re- nal biopsy demonstrated focal glomerular sclerosis.
??Dr Chernow: The patient had a nephrotic syndrome characterized by heavy proteinuria (greater than 3.5 g/24 h), hypoalbuminemia, and edema. Lipi- duria and hyperlipidemia also character- ize the disease. Hypertension may or may not be present and is usually related to the glomerular disease. Patients also have de- creased thyroxin and thyroid binding glo- bulin. However, most remain euthy- roid.1J,3 Many are hypercoagulable and are at risk for renal vein thrombosis and pulmonary embolus. 4~5,7 When this patient presented, the differential diagnoses caus- ing peripheral edema and chest pain in a young man had to be considered.
There are four common causes for pe- ripheral edema: congestive heart failure, cirrhosis, nephrotic syndrome, and idio- pathic. In the latter, the edema may be persistent or episodic. The term cyclic edema refers to the episodic form. Other causes include pregnancy, hypothyroid- ism, venous stasis, and certain drugs. A thorough history and physical examina- tion, along with a few simple laboratory studies such as liver function tests, urinal- ysis, and chest x-ray study will usually in- dicate the cause.
Chest pain in a young individual is a relatively common occurrence. Although ischemic pain is unlikely, cardiac causes such as mitral valve prolapse and pericar- ditis must be considered. The latter may mimic pulmonary causes. Pneumonia and pneumothorax also frequently cause chest pain in young patients. Other noncardiac causes of atypical chest pain include eso- phageal spasm, rupture, and reflux. Mm
culoskeletal causes include costochon- dritis or Tietze’s syndrome.
??A physician: What was the etiology of this patient’s nephrotic syndrome?
??lDr Chernow: The nephrotic syndrome is classified as either primary or second- ary. The pathology or etiologies in each group are summarized in the Table. Since the fundamental cause of the renal lesion in primary glomerular diseases is un- known, the etiology is grouped according to renal pathology. 2,3~12 Secondary glo- merular diseases have extrarenal involve- ment as the cause for the renal pathology. These include drugs and nephrotoxins, al- lergens, infections, neoplasms, systemic and collagen vascular diseases, hereditary, and others grouped into a miscellaneous category, It is interesting to note that focal glomerular sclerosis is a primary glomeru- lar disease and has also been associated with intravenous heroin use. However, there was nothing in our patient’s history or physical to suggest a secondary cause of his renal disease. He thus presumably had a primary glomerular disorder of idi- opathic etiology.
??A physician: Why was a renal biopsy performed?
??Dr Chernow: A biopsy is necessary to classify the renal disease. This may have therapeutic implications as well as assist in finding a possible secondary cause. There is less need for a biopsy in children as 80% of the renal lesions are minimal changes that respond well to steroid therapy. Mini- mal change disease accounts for only 20% of adult pathology.6+sJ2 This patient had focal glomerular sclerosis on renal biopsy.
??A physician: What is characteristic about focal glomerular sclerosis?
??lDr Chernow: The first description of focal glomerular sclerosis was by Arnold Rich in 1957.9 Since that time much con-
Peripheral Edema and Chest Pain 417
Table. Conditions Associated With Nephrotic Syndrome
troversy has centered on whether the le- sion is a distinct entity or a progression from other diseases. The disease accounts for approximately 10% to 15 070 of patients with idiopathic nephrotic syndrome. The lesion is characterized by the presence of intracapillary deposits of periodic acid Schiff s positive hyaline material. Mesan- gial proliferation may be seen and implies a poor prognosis. Electron microscopy re- veals diffuse foot process alterations. Complement and IgM deposits have been noted in areas of sclerosis, although se- rum complement remains normal. Clini- cally, the disease has a male predominance and affects all age groups. Hypertension and decreased renal function are com- mon. Fifty percent of patients progress to renal failure in 10 years. The disease is usually steroid resistant, and the role of immunosuppressive therapy is unclear. There is a high recurrence after renal transplantation.2~3~8~‘2
??A physician: Why are patients with nephmtic syndrome hypercoagulable?
??Dr Chernow: There are a number of risk factors for hypercoagulation with the nephrotic syndrome, although the exact cause remains unclear.15 Many patients are relatively immobile and on corticoste- roids. Overzealous use of diuretics in the face of an already decreased plasma vol- ume also may contribute to the risk of thromboembolus. Of particular interest are the changes in the coagulation cascade (Figure) that occur in the nephrotic syn- drome. Factor VIII procoagulant activity is generally greatly elevated in most pa- tients with nephrotic syndrome. This is thought to reflect increased synthesis by endothelial cells and contraction of the in- travascular distribution of this high mo- lecular weight protein. Factor V pro- coagulant activity is elevated for the same reasons with nephrotic syndrome, al- though not to the same degree as factor VIII. The increased plasma fibrinogen, frequently seen in patients with nephrotic syndrome, often correlates with increased cholesterol levels. Increased hepatic syn- thesis and contracted intravascular distri-
418 Steven M. Chemow and Kenneth V. lserson
Intrinsic Pathway
Extrinsic Pathway
XII I
TissuqFactor
XII VII
0 Xl-Xb tt
&-
IX -IX,+VIII+ ~~~~J~‘+Ca”
ft Fibrinogen 0b Fibrin
I( XIII,
Crosslinked Fibrin
Figure. Coagulation factors affected in the nephrotic syndrome. The coagulation cascade is shown for clarity. tt Markedly increased in nephrotic syndrome; t increased in nephrotic syn- drome.
bution are believed to be the mechanism for this increase.5~‘3~14~15
A deficiency of antithrombin III, a ma- jor inhibitor of thrombin, has also been implicated in the hypercoagulable state of the nephrotic syndrome.4 The effect of this deficiency is markedly increased in the presence of heparin.rO Familial defi- ciencies of antithrombin III are associated with hypercoagulable states, which lead to such events as primary mesenteric venous thrombosis and deep-vein thrombosis.” Conflicting data exist as to whether there is a true deficiency, rather than just
an effective decrease of antithrombin III activity in patients with nephrotic syndrome. 15
??Dr Iserson: This patient’s hospital course was benign. He was started on anticoagulation therapy for his pulmo- nary embolus. After discharge from the hospital, it was continued on an outpa- tient basis. Steroid therapy, begun on the outside chance of renal improvement, was of no benefit. He continues to be followed as an outpatient.
REFERENCES
I. Glassock R: Management of the idiopathic nephrotic syndrome. Conuib Nephrol 1980; 23:158-180.
thromboses in the nephrotic syndrome. Am J Med 1978; 65:607.
2. Glassock RJ, Cohen AH, Bennett CM, et al: Primary glomerular disease, in Brenner BM, Rector FC Jr (eds): The Kidney. Philadelphia, WB Saunders, 1981, pp 1351-1492.
3. Heptinstall RH: The nephrotic syndrome, in Heptinstall RH (ed): Pafhology of the Kidney, 3rd ed, vol II. Boston, Little, Brown and Co, 1983, pp 637.
5. Kendall AG, Lohmann RC, Dossetor JB: Nephrotic syndrome: A hypercoagulable state. Arch Intern Med 1971; 127:1021-1027.
7. Llach F, Koffler A, Finck E, et al: On the inci- dence of renal vein thromboses in the nephrotic syndrome. Arch Intern Med 1977; 137:333- 336.
4. Kauffman FH, Veltkamp JJ, Van Tilburg NH, et 8. Newman JW, Tisher CG, McCoy RC, et al: Fo- al: Acquired antithrombin III deficiency and cal glomerular sclerosis: Contrasting clinical pat-
Peripheral Edema and Chest Pain 419
9.
10.
11.
12.
terns in children and adults. Medicine 1976; 55:67-87. Rich AR: A hitherto undescribed vulnerability of the juxta-medullary glomeruli in lipoid nicro- sis. Bull Johns Hopkins Hosp 1957; 100:173- 186. Rosenberg RO: Actions and interactions of anti- thrombin and heparin. N Engl J Med 1975; 292:146-151. Schafer AI: The hypercoagulable states. Ann In- tern Med 1985; 102:814-828. Tisher CC: Glomerular disorders, in Wyngaar-
13.
14.
15.
den JB, Smith LH Jr: Cecil T&book of Medi- cine. Philadelphia, WB Saunders, 1982, pp 520-534. Thompson AR: Factor XII and other hemostatic protein abnormalities in nephrotic syndrome pa- tients. Thromb HaetnosIas 1982; 48:27-32. Thomson C: Changes in blood coagulation and fibrinolysis in the nephrotic syndrome. Q J Med 1974; 43:399-407. Vaziri ND: Nephrotic syndrome and coagulation and fibrinolytic abnormalities. AM J Nephrol 1983; 3: 1-6.
