- Fat embolism in the patient occurred within only 2.5 hours, but no obvious injuries were observed.
- The patient had fat embolism in multiple organs, not just in the lungs.
- Advanced age, hypertension, and hyperlipidemia may be risk factors for nontraumatic fat embolism.
- During the forensic pathological examination, attention should be paid to the detection of fat embolism in other organs not just the lungs.
Fat embolism refers to lipomicrons entering the blood circulation and blocking the microvascular and capillary vessels. It is mostly caused by fractures of the long bones or pelvis.1,2 The symptoms often appear 24 to 72 hours after injury, including pulmonary symptoms (shortness of breath, difficulty breathing), neurological symptoms (disordered consciousness, lethargy, coma), and dermatological symptoms (petechiae, rash), which together are known as fat embolism syndrome (FES).3,4
Fat embolism occurs usually after a wound, when lipids are released from the damaged bone or soft tissue into the blood, and the blood circulates into small blood vessels or capillaries, causing blood vessel embolism in the lung or brain.5–7 However, some patients with nontraumatic factors, such as hepatocellular carcinoma,8 bone marrow necrosis,9 sickle cell anemia,10,11 long-term usage of corticosteroids,12 fatty liver,13 diabetes,14 and renal angiomyolipoma,15,16 have also been reported to experience fat embolism. Hulman17 suggested that nontraumatic fat embolism occurs because of the accumulation of C-reactive protein (CRP) in the blood, which causes the aggregation of chylomicrons and very low-density lipoprotein, forming fat globules, which then form a thrombus to block blood vessels. The increase in the level of CRP can be caused by trauma, inflammation, tumors, myocardial infarction, sepsis, and so on. Sakashita et al8 reported a case of nontraumatic fat embolism in the lungs and kidneys of patients with liver cancer, indicating that nontraumatic fat embolism can occur in organs other than the lungs and brain. Thin-layer chromatography was used in that study to analyze the lipid composition of the fat thrombosis and found that the fat emboli may be related to triglycerides (TGs). Schulz et al13 reported the cases of 2 fatty liver patients who experienced nontraumatic fat embolism in the lungs, kidneys, heart, brain, and thyroid, which suggested that fat embolism is associated with hepatic steatosis. Nichols et al18 reported that a 2-year-old child experienced FES of the lungs, kidneys, and brain due to long-term abuse, although there were no fractures or extensive tissue damage, and the FES was thought to be caused by the combination of trauma and lipid emulsification in the blood. However, the mechanism underlying nontraumatic embolism is unclear.
This article reports a case of an elderly woman with hypertension and hyperlipidemia who died of systemic multiorgan fat embolism under stressful conditions and discusses the possible risk factors for nontraumatic fat embolism.
An 88-year-old woman with a history of hypertension for more than 10 years was suspected to have been knocked down by a car. At the time of the event, she was able to stand on her own and was conscious. Because there was no obvious trauma, the driver sent her home. After approximately 2 hours, she lost consciousness and became unresponsive. She was sent to the emergency department with no heartbeat or respiration. After half an hour of rescue attempts, her heartbeat did not recover, and she was declared dead. An autopsy was performed 1 day after she died.
The subject was an elderly woman with a corpse length of 157 cm, no abnormal development, poor nutrition, and a 5 × 2-cm subcutaneous hemorrhage under the right knee joint (Fig. 1).
The brain weighed 1350 g. A 2 × 1 × 0.5-cm-old cerebral infarction was observed in the right cerebellum parenchyma. The left and right lungs weighed 500 and 800 g, respectively. The cut surface of the lungs showed mild congestion and edema. The heart weighed 300 g. The left anterior descending coronary artery showed mild atherosclerosis with 10% luminal stenosis. The circumflex branch showed mild atherosclerosis with 25% luminal stenosis. The right coronary artery showed mild atherosclerosis with 25% luminal stenosis. The liver weighed 980 g. The hepatic capsule was pink-tan on the surface, and the cut surface showed congestion and edema. The spleen weighed 80 g, and the cut surface showed congestion and edema. The pancreas weighed 100 g, and the cut surface showed congestion and edema. The left and right kidneys weighed 120 and 100 g, respectively, and both cut surfaces showed congestion and edema.
Some small vessels in the subarachnoid space showed wall thickness and hyaline changes under the microscope after hematoxylin and eosin staining, and an old infarct was seen in the cerebellar parenchyma. Both sides of the lung interstitium showed signs of congestion. The microvasculature showed comprehensive vacuolation and beaded-voculation patterns in the capillary vessels. Some alveolar walls were disrupted, and some alveoli showed changes related to emphysema. Part of the liver showed fatty changes. Few glomeruli showed sclerosis. Protein casts were observed in part of the renal tubes. Some small arteries showed wall thickness and hyaline changes in the renal parenchyma. Some splenic arteries showed wall thickness and hyaline changes in the spleen parenchyma. Fat staining of frozen tissue sections of the brain, lung, liver, kidney, and pancreas (Sudan III staining) showed distinct fat embolism in multiple organs, including the brain, lungs, kidneys, liver, and pancreas, according to Falzi classification.19 Small blood vessels and capillaries in the lung tissue, glomerular capillaries, and small blood vessels in the brain, liver, and pancreas had multiple fat emboli. A large number of fat droplets stained orange were disseminated throughout every field of vision (Fig. 2). The Sudan III staining method has been used at our institution for decades in cases of suspected fat embolism. It is an advanced and effective staining method for observing fat embolism. In addition, oil Red O, Sudan Black, and osmium tetroxide methods can also be used for lipid staining in cases of fat embolization syndrome.20,21
The results of postmortem biochemistry tests of the heart blood showed the following: hemoglobin, 110 g/L (110–150 g/L); hemoglobin A1c, 6.8%; TG/high-density lipoprotein, 0.5 mmol/L (0.9–2.19 mmol/L); low-density lipoprotein (LDL), 16.31 mmol/L (<3.12 mmol/L); total cholesterol, 6.81 mmol/L (3.36–5.78 mmol/L); TG, 3.17 mmol/L (0.45–1.81 mmol/L); CRP, 5.96 mg/dL (≤1 mg/dL); and free fatty acid (FFA), 3.8 mmol/L (0.3–0.9 mmol/L).
No alcohol or common drugs were found.
The exact mechanism of fat embolism remains unclear. There are 2 main hypotheses at present: the mechanical theory and the biochemical theory. The mechanical theory suggests that disrupted fat cells in the bone marrow or adipose tissue enter the broken veins, thereby entering the systemic circulation, causing fat embolism.1,22 Fat embolism caused by traumatic fractures can mostly be explained by mechanical theory.
The biochemistry theory suggests that under stress and the release of catecholamine, the levels of toxic metabolites such as FFA and CRP increase,17,23 leading to vascular endothelium injury, increased vessel permeability, and inhibition of pulmonary surfactants, which are related to acute respiratory distress syndrome or indirectly cause the accumulation of chylomicrons and LDL, leading to the formation of fat embolism.24 This is the commonly accepted theory of the mechanism underlying nontraumatic fat embolism. Moreover, Hulman17 suggested that nontraumatic fat embolism was related to the increase in the CRP level in the blood, which can be caused by various factors such as trauma, inflammation, tumors, myocardial infarction, and sepsis. Sakashita et al8 performed a lipid analysis on a case of liver cancer combined with nontraumatic fat embolism and suggested that fat thrombosis formation is related to TGs. Fat embolism has also been reported in hip surgery, osteomyelitis, alcoholic fatty liver disease, heat exposure, cardiopulmonary bypass surgery, decompression sickness, diabetes mellitus, corticosteroid therapy, parenteral lipid infusion, sickle cell disease, hemorrhagic pancreatitis, and carbon tetrachloride poisoning. We performed full differential diagnosis and eliminated all the aforementioned possible causes. The deceased had scattered hepatocyte fatty degeneration, but it was limited and far from reaching the level of fatty liver.25
Many reports claim that the fat embolism effect only occurs in the lungs because the trauma causes lipids to leak from injured vessels and enter the lungs via the blood. There are reports claiming that isolated pulmonary fat embolism is association with cardiopulmonary resuscitation.26,27 However, some nontraumatic fat embolism occurs not only in the lungs but also in many other organs, such as the brain, liver, kidneys, pancreas, and thyroid. In this case, the fat embolus in the deceased was also found in the brain, liver, kidney, and pancreas in addition to the lungs, leading to the conclusion that the occurrence of nontraumatic fat embolism may be systemic rather than localized to the lungs.
Fat embolism is one of the causes of death due to superficial soft tissue injuries.28,29 In this case, the deceased had only a small subcutaneous hemorrhage on the extensor side of the right knee joint and no fracture or massive soft tissue contusion. We flayed the skin to check the possible positive areas, but the fat embolism occurred in such a short time and no other subcutaneous hemorrhages were seen. Therefore, the mechanical theory could not explain the fat embolism in multiple organs of the deceased in this case.31 The deceased in our case was an 88-year-old woman with hypertension for more than 10 years. The results of the blood biochemistry tests showed different degrees of elevation of her LDL, cholesterol, TG, FFA, and CRP, suggesting that the deceased may have had dyslipidemia before her death. According to the test results and biochemistry theory, we presume that the deceased in this case experienced the accumulation of lipids such as chylomicrons and very low-density lipoprotein in the blood caused by stress after being hit by a car and frightened. Thus, the possibility of systemic fat embolism is established, and it is thought that under stressful conditions, aging, hypertension, and hyperlipidemia may be risk factors. Symptoms of pulmonary fat embolism often occur 24 to 48 hours after injury, but there are also reports of fulminant fat embolism occurring within a few hours after injury. Lever et al32 presented the case of a 72-year-old male patient with osteoarthritis and coronary amyloidosis who died of pulmonary fat embolism 2 hours after an elective right cementless total hip arthroplasty. İlhan et al33 reported that an 84-year-old woman died within 3 hours after a car crash due to multiple fractures combined with extensive fat embolism in the lung. In 17 cases of nontraumatic fat embolism (Table 1), 3 cases occurred within 24 hours, 2 of which involved multiple-organ fat embolism. With regard to fulminant fat embolism, even with the existence of traumatic factors, individual risk factors cannot be ignored.
This article reports a case of multiorgan nontraumatic fat embolism in a patient with hypertension and hyperlipidemia exposed to stressful conditions, and the results suggest that factors such as advanced age, hypertension, and hyperlipidemia may be risk factors for nontraumatic fat embolism. The diagnosis of nontraumatic fat embolism may involve the nature of death and the division of responsibilities. During the forensic pathological examination, attention should also be paid to the detection of fat embolism in other organs and not just the lungs. Multiorgan fat embolism could be a critical factor in the differential diagnosis of traumatic or nontraumatic fat embolism. The pathological mechanism underlying nontraumatic fat embolism and the specific risk factors are still unclear, and further case collection and research are needed.
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