IATROGENIC PULMONARY FAT EMBOLISM AFTER SURGERY IN A PATIENT WITH FATTY LIVER JATROGENA MASNA EMBOLIJA PLUĆA POSLE HIRURŠKE INTERVENCIJE KOD BOLESNIKA SA MASNOM JETROM

Introduction. Fat embolism refers to the presence of fat globules in the lung parenchyma and its peripheral circulation. Obstruction of the lung vessels by fat emboli can lead to acute cor pulmonale when the compensatory capabilities of the pulmonary vasculature are exceeded. Case report. We presented a case of a 78-year old man who suffered a dissection of abdominal aortic aneurysm. Urgent surgical procedure was performed and aneurysm replaced with aortobifemoral bypass grafting using a Dacron graft. Despite the procedure the patient died the following day. The autopsy revealed that the cause of death was hypovolemic shock. There were no bone fractures (also no fractures of ribs and sternum from cardiopulmonary resuscitation) or injuries of the subcutaneous fat tissue or other organs (besides those from the surgery). However, additional autopsy findings included fatty liver change, small liver hemorrhages (confirmed microscopically), as well as a presence of fat droplets in the hepatic veins, as well as in the pulmonary vessels, i.e. pulmonary fat embolism [confirmed with hematoxylin/ eosin (H/E), and Sudan III staining], which could be the contributing cause of death. Conclusion. The presented case indicates that pulmonary (or even systemic) fat embolism should be considered as the possible iatrogenic cause of unexpected and unexplained death in the cases where elective surgical procedures were performed in patients with fatty liver change. Pathologists must be aware of this possibility, since it is not easily recognized on routine H/E staining, and some of the special staining technique should be applied.


Introduction
A presence of fat droplets in the lung circulation presents a pulmonary fat embolism.With the obstruction of the sufficient percent of pulmonary vessels by the fat emboli, with the exceeding of its compensatory capabilities, acute right heart failure may develop [1][2][3].
Commonly, lung fat embolism after sustained trauma is a subclinical event: droplets of fat are sucked into the venous system at a site of fracture and then get stuck in the pulmonary circulation.Once entering the lungs, fat globules might enter the systemic circulation, reaching different organs.The clinical manifestation of systemic fat embolism, primarily with progressive respiratory distress and a deterioration in central nervous system function is called fat embolism syndrome [2].Although most commonly associated with trauma [1][2][3], there are some described cases of non-trauma related fat embolism [4][5][6][7][8][9][10].We presented one such case, most probably caused iatrogenicly, in a setting of previously existing fatty liver change.

Case Outline
A 78-year-old man was admitted to the hospital, after being transferred from a regional medical center with the CT confirmed rupture of abdominal aortic aneurysm.The diameter of aneurysm was 87x79 mm and the rupture was localized on the right lateral side of abdominal aorta, just below the renal arteries.The urgent surgical procedure was performed: open transperitoneal resection of the ruptured part of the aortic aneurysm, which was replaced with a Dacron graft aorto-bifemoral bypass.During the entire course of the operation, the patient was hypotensive.Several hours after the procedure, the patient died with the clinical signs of hemorrhagic shock.
The autopsy was performed the following day.The macroscopic examination showed signs consistent with hemorrhagic shock, as well as signs of the described surgical procedure.
The signs of severe atherosclerosis were most prominent in the aorta, and slightly less in coronary arteries.The lungs were livid and heavy (total lung weight was about 1600 g), while the liver showed signs of fatty change, as well as small subcapsular bleedings on its surface.There were no bone fractures (including with the excepiton and also no fractures of ribs and sternum from CPR) or injuries of the subcutaneous fat tissue or other organs (besides those from surgery).Microscopic examination (H/E staining) of the liver showed moderate to severe fatty change in hepatocytes, but also small subcapsular fresh hemorrhages (Fig. 1a, 1b).Examination of the lungs, however, revealed the possible presence of fat droplets in the pulmonary vessels, i.e. pulmonary fat embolism (Fig. 2a).
Therefore, additional Sudan III-staining was performed on samples taken from the lungs, as well as the brain, kidneys and liver.The histological findings of frozen sections of the lungs confirmed the pulmonary fat embolism: red sausage-shaped or rounded, multiple, disseminated fat emboli were present in every microscopic field (Fig. 2b, 2c, 2d).These findings corresponded with the moderate, second grade of lung fat embolism, according to the classification proposed by Felicia et al.Fat droplets were not found in the brain and kidneys.On the other hand, this special staining confirmed fatty change in the hepatocytes, but also showed the presence of multiple fat globules in middle caliber hepatic veins (Fig. 1c, 1d).The main cause of death was attributed to hemorrhagic shock due to rupture of abdominal aortic aneurysm, while pulmonary fat embolism was the contributing factor.

Discussion
Fat embolism is most commonly associated with trauma (i.e.fractures) 1-3, however there is relatively small number of described cases of fat embolism in the absence of trauma, associated with alcoholic or steroid-induced fatty liver, acute hepatic necrosis or diabetes 4-8, and only a few papers of postoperative fat embolism 9.One of the studies found quite surprising incidence of fat embolism in cases of sudden deathin 34 out of 65 cases 10.
Fat embolism represents as the mechanical blockage of the blood vessels by circulating fat globules.Lungs are most commonly affected organ, but fat embolism also might affect organs such as brain, retina, and skin [11].Systemic fat embolism syndrome is defined as clinical manifestation of systemic fat embolism [2], and it could be potentially fatal complication of trauma or surgical procedure.Typical occurrence is 12 to 72 h after the surgery, presenting with progressive respiratory insufficiency, consciousness disorders and petechiae.Different neurological disorders may be present, ranging from mental confusion to altered level of consciousness, and also transient and reversible disorders manifesting as generalized convulsions and focal deficits [11].
There are several theories that explain the pathophysiological features of far embolism.So called infloating theory, or the traditional view of fat embolism explains that fat is physically pushed into the veins after trauma, most typically after fracture of long bones [1].Lipase theory explains that trauma causes an elevation of plasma lipase titer, which then destabilizes circulating fats by de-emulsification, saponification and mobilizing lipid stores.A second biochemical theory invokes the possible histotoxic effects of free fatty acids from bone marrow.Finally, shock and coagulation theory is based on noting that many patients who develop post-traumatic fat embolism are also hypovolemic.
Hypovolemia leads to a slowing down of circulation with "slugging" of blood components and forming of micro aggregates in the lungs.Tissue trauma worsens this by damaging vessels' intimal layer causing platelet activation.Fat from bone marrow then might provide a possible adherence surface for the activated platelets [1].
In the presented case, in the absence of fractures or extensive necrosis of fat tissue, lung fat embolism could be explained by some of the latter theories.However, both gross and microscopic findings of small subcapsular hemorrhages in the liver, together with the presence of fat globules and fatty changed hepatocytes in hepatic veins (Fig. 1) indicated a somewhat different mechanism.Most probably, the mechanical pressure on the fatty changed liver during the urgent surgical procedure of abdominal aorta, led to liver injury with small hemorrhages and release of fat from injured hepatocytes.Fat emboli from hepatocytes then entered venous circulation, and finally led to pulmonary fat embolism (Fig. 2).Pulmonary fat embolism could have additionally exacerbated the existing hypovolemic shock.Although undoubtedly the main cause of death in the presented case was hypovolemic shock due to abdominal aortic aneurysm rupture, iatrogenic pulmonary fat embolism could be considered as additional, contributory cause of death.
There is as yet no specific treatment for either pulmonary embolism or fat embolism syndrome [11].However, it is essential that support measures, especially in treating adult respiratory distress syndrome, such as oxygen therapy or mechanical ventilation, be taken in more severe cases.

Conclusion
The presented case indicates that iatrogenic pulmonary (or even systemic) fat embolism should be considered as the possible cause of unexpected and unexplained death in the cases where elective surgical procedures were performed in patients with fatty liver change.
The pathologists must be aware of this possibility, since it is not easily recognized on routine H/E staining, and some of the special staining technique should be applied, i.e. the one must search for fat embolism in order to establish the correct diagnosis.Online First April, 2018.

Fig. 2 -
Fig. 2a H/E staining of the lungs shows the presence of fat globules in small pulmonary vessels.b,c,d Frozen Sudan III-stained sections of the lungs show red, drop, sausage-and branching-shaped fat emboli in pulmonary vessels.