|Year : 2016 | Volume
| Issue : 3 | Page : 171-174
Infiltration and Fat Droplet Phagocytosis by Macrophages in the Alveoli may be the Most Likely Characteristics of Fat Embolism
Bin Wang1, Fu Zhang2, Ning Xiao1, Xiang Xu1, Qi Wang1, Xiao-Hui Tan1, Tao Wang1, Hui-Jun Wang1, Dong-Ri Li1
1 Department of Forensic Medicine, Southern Medical University, Guangzhou 510515, PR China
2 Guangdong Public Security Department, Key Laboratory of Forensic Medicine, Guangzhou 510050, Guangdong Province, PR China
|Date of Web Publication||30-Sep-2016|
Department of Forensic Medicine, Southern Medical University, No. 1838, Guangzhou 510515, Guangdong Province
Source of Support: None, Conflict of Interest: None
We report a case of nontraumatic fat embolism syndrome with large amounts of macrophages with phagocytized fat droplets in the alveoli. A 46-year-old male presented with a glass-cut injury in his little finger. The wound was debrided and sutured at the hospital, but he was found dead 43 h after treatment. Autopsy results showed that the patient had steatohepatitis, accompanied by histological findings of fat droplets in the pulmonary capillaries. In the alveoli, we found a large number of macrophages with phagocytized fat droplets that showed stained. To the best of our knowledge, this is the first report of such a case, and the paper proposes that fat droplets phagocytized by a large number of macrophages may be a characteristic feature of fat embolism, which may be relevant to forensic pathology practice.
Keywords: Fat droplet, fat embolism, forensic pathology, macrophage, nontraumatic
|How to cite this article:|
Wang B, Zhang F, Xiao N, Xu X, Wang Q, Tan XH, Wang T, Wang HJ, Li DR. Infiltration and Fat Droplet Phagocytosis by Macrophages in the Alveoli may be the Most Likely Characteristics of Fat Embolism. J Forensic Sci Med 2016;2:171-4
|How to cite this URL:|
Wang B, Zhang F, Xiao N, Xu X, Wang Q, Tan XH, Wang T, Wang HJ, Li DR. Infiltration and Fat Droplet Phagocytosis by Macrophages in the Alveoli may be the Most Likely Characteristics of Fat Embolism. J Forensic Sci Med [serial online] 2016 [cited 2020 Mar 28];2:171-4. Available from: http://www.jfsmonline.com/text.asp?2016/2/3/171/191472
| Introduction|| |
Fat embolism syndrome (FES) develops when 10-40 μm fat droplets are released into the circulation due to bony or soft tissue trauma occurs, or when fat droplets have coalesced abnormally within the circulation due to nontraumatic disorders.  FES is dangerous and rapid in onset. The mortality rate is high, about 10%-25%.  The mortality rate in cases of sudden onset is higher than 50%.  FES is always found following fracture of the long bones or major trauma. , It is also associated with orthopedic surgery, especially in bone- and joint-related surgeries, including operations for bone fractures with interlocking intramedullary nailing  and spine fusion surgery.  The incidence rate of FES after hip and knee arthroplasty is about 0.13%.  Liposuction  and dystocia  may also induce FES. However, FES has rarely been reported in a variety of nontraumatic conditions, such as fatty liver, ,, diabetes mellitus,  acute pancreatitis, , sickle cell disease, , osteomyelitis, and sepsis. ,,,
The etiology of FES is multifactorial and complex. Two main factors have been theorized as responsible for the pathophysiology of FES. The mechanical factor of trauma causes the release of fat droplets, due to the disruption of fat cells in fatty marrow or adipose tissue. Then, the fat droplets enter the venous system and obstruct the pulmonary vascular bed.  The biochemical factor generates fat droplets from circulating blood lipids. The metabolic response to stress alters the physiologic emulsion of fat in plasma. 
The diagnosis of FES is usually based on a history of trauma and the clinical symptoms. Transparent vacuoles can be found with hematoxylin and eosin (H and E) staining, and are confirmed when the fat droplets are stained with Sudan III, which is direct evidence for the diagnosis of FES. In clinical diagnosis, some reports stated that fat staining of sputum, bronchoalveolar lavage fluid testing, and thrombocytopenia can be important in the diagnosis of fat embolism. ,,, In the absence of a relevant medical history, and without significant numbers of fat vacuoles on H and E staining, the diagnosis of FES can be difficult. This article describes the case of a patient with fatty liver who died of a nontraumatic fat embolism. Only a small area of lipid accumulation as vacuoles was observed with H and E staining. However, in the alveoli, we found a large number of macrophages with phagocytized fat droplets that were stained. To the best of our knowledge, this is the first report of such a case, and the paper proposes that fat droplets phagocytized by a large number of macrophages in the alveoli may be a characteristic feature of fat embolism, which is relevant to forensic pathology practice.
| Case Report|| |
A 46-year-old healthy male with no history of high blood pressure or diabetes presented with an accidental glass-cut of his little finger. The wound was debrided and sutured at the hospital on the 27 th at night. By the afternoon of the 28 th , the patient had a fever. Vital signs included the following: Temperature, 38.3°C; pulse, 88/min; respiratory rate, 20/min; and blood pressure, 130/80 mmHg. He had dizziness and weakness. Routine tests showed the following: White blood cells, 0.8 × 10 9 /L; neutrophils, 41.0%; mononuclear cells, 23.5%; and platelets, 42 × 10 9 /L. At 9 am on the 29 th , his blood pressure decreased, and he had cold extremities and shortness of breath. His heart rate was 132/min, blood pressure was 80/40 mmHg, respirations 34/min, and SaPO2 was 68%-70%. Physical examination showed decreased breath sounds in the right chest. The differential diagnosis included septic shock, pulmonary embolism, and hematopathy. He died at 5 pm on the 29 th .
A complete autopsy was performed on a well-developed and well-nourished male (height, 174 cm) 24 h after death. A sutured wound was present in his left little finger [Figure 1]. About 160 ml of fawn-colored fluid was found in his thoracic cavity. The left lung weighed 1300 g, and the right lung weighed 1920 g. Macroscopically, the surface of the lungs showed petechiae and the sectioned lungs showed severe edema. The liver weighed 2420 g (normal liver weight is 1369 ± 369 g in an 18-59 years old).  The surface and section of the liver had a yellowish-brown color. The remaining organs showed congestion and edema.
|Figure 1: The sutured wound was found in the little finger on the left hand|
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The alveolar spaces showed severe congestion, and the alveolar walls were ruptured. Large numbers of monocytes and sloughed Type II epithelial cells were found in the alveoli. Transparent vacuoles with a string-of-beads appearance were found in small vessels of the lungs and capillaries in the alveolar walls. Fat droplets were found in small vessels within the alveolar spaces and the cytoplasm of monocytes in the alveoli with Sudan III staining [Figure 2]. No fat droplets were found in other organs. Diffuse hepatic steatosis suggestive of steatohepatitis was present [Figure 3].
|Figure 2: Histological findings ([a and c]: H and E on paraffin embedded sections, ×200, [b and d]: Sudan III staining on frozen sections, ×200). (a) Transparent vacuoles presented changes of string-of-beads in small vessels of lungs and also capillaries of alveolar walls. (b) Fat staining reveals numerous brown fat droplets in the capillaries of alveolar walls. (c) Infiltration of a large number of monocytes and the shedding of Type II epithelial cells were found in alveolus. (d) Fat droplets were found in cytoplasm of monocytes in alveolus with Sudan III staining|
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|Figure 3: (a) The surface of liver presented a yellowish-brown color. (b) Diffuse hepatic steatosis like steatohepatitis was presented (H and E on paraffin embedded sections, ×50)|
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General screening of blood and urine samples with headspace gas chromatography (GC) with flame ionization detection, GC-mass spectrometry (MS), and liquid chromatography-high resolution MS,  excluded the presence of alcohol and drugs.
| Discussion|| |
The incidence of FES is highest following trauma, especially in the case of long-bone fractures. However, FES has been reported in many other conditions and is difficult to diagnose due to the lack of reliable criteria.  Through changes in chemical mediators, emulsification of blood lipid becomes unstable and induces the release of fat droplets.
Shock is also considered a cause of FES. , Stelzig and Kössling have discussed hepatogenic fat embolism in their extensive studies. They believe that atraumatic and traumatic ruptures of hepatic fat cysts, toxic-necrotizing liver changes, and extrahepatic factors (phenomena of shock and changes in blood content, especially lipase activity) are responsible for fat embolism.  Even in cases with excessive fatty degeneration of the liver, usually only a minimal transfer of lipids from the liver into the lungs was noted in their studies. 
In experiments on rats with fatty livers, pulmonary fat embolism was induced by elevation of core body temperature. The possibility of FES onset increases with elevation of body temperature. , Moreover, in patients with fatty liver, fulminant hepatitis, viral hepatitis, and other stress states can induce the onset of pulmonary fatty embolism. ,
Nontraumatic fatty embolism is easily overlooked and requires greater attention due to the risk of rapid onset and sudden death. In the forensic evaluation, an obvious traumatic history and sudden onset of neurologic and pulmonary complications, accompanied by histological findings of fat droplets in pulmonary capillaries, simplifies the diagnosis of fatty embolism.
However, if the relevant clinical information is lacking and no deposition of fat droplets is found, misdiagnosis is likely. The possibility of fatty embolism requires a high degree of suspicion, especially in cases with nontraumatic fatty embolism, if any contributory factors are found during autopsy or case investigation.
A complete autopsy and serologic and toxicologic examination excluded the possibility of sudden onset of cardiovascular and neurovascular disease in this case. Moreover, the possibility of intoxication was also excluded from this study. We noted that there were some fat droplets in bilateral pulmonary parenchymal capillaries, but the involved area was relatively small.
Specific pathological findings included massive infiltration of monocytes into the bilateral pulmonary alveolar spaces, pulmonary edema, alveolar wall rupture, and intra-alveolar hemorrhage. With this clinical information, decreased numbers of monocytes and platelets were found. Therefore, we considered the possibility of fat embolism. A small amount of fat droplets had entered the alveolar capillaries, and a large number of monocytes had infiltrated into the bilateral pulmonary spaces and ingested fat droplets. The final diagnosis was fat embolism after other causes of death were excluded from this study.
This case progressed to death following a cut on the finger with a piece of glass, resulting in a small wound and only slight bleeding. Because the vital signs were stable after admission and proper medical treatment was administered, we excluded FES triggered by the wound.
According to clinical history, the deceased had no recent surgery, and no FES-related diseases were found, such as acute pancreatitis or diabetes mellitus. However, his family reported that he had an alcoholic history for many years, and steatohepatitis was found on forensic pathology examination. Therefore, FES caused by acute pancreatitis, diabetes mellitus, and iatrogenic reasons was excluded. We decided that the possibility of bilateral pulmonary FES caused by fatty liver could not be ruled out.
In this case, the deceased had a fatty liver, which could have been the cause of FES. Moreover, he had a fever and was injured while working. We could not exclude the possibility of other unknown factors, including FES caused by fever or a stress state. Therefore, further research and evaluation were needed.
Clinical examination showed an obvious decrease in the numbers of monocytes and platelets, and many monocytes had infiltrated into the alveoli and ingested fat droplets, as shown with Sudan III staining. The fat droplets had changed from a halo shape to granules, with no observation of monocytes with ingested fat droplets on H and E staining. This was related to the reduced numbers of monocytes and the fact that the area with fatty droplets was relatively small in the capillaries of the pulmonary spaces.
According to the literature, staining of aspirated sputum and bronchial lavage fluid can be used for clinical diagnosis of FES. , If a large number of macrophages with phagocytized fat droplets are found in sputum or bronchial lavage fluid, FES can be diagnosed, but this method has not been reported in the forensic pathology literature. The findings in this study have great significance for both clinical medicine and forensic practice. Further research on animal models should be performed to explore this mechanism of FES.
This is the first report to suggest that fat droplets phagocytized by numerous monocytes may be an important feature of fat embolism, with relevance to forensic pathology practice. It is essential to combine clinical and forensic examination to diagnose fat embolism. Our results suggest that clinicians and forensic pathologists should be more aware of fat embolism, especially in nontraumatic conditions. Reduced numbers of monocytes and platelets may indicate the possibility of fat embolism in the lungs. When we do not suspect the presence of factors contributory to fat embolism, fat staining of phagocytic monocytes, even in the absence of lipid vacuoles, may provide significant evidence for FES in forensic diagnosis.
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Conflicts of interest
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