Fat embolism syndrome pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Feham Tariq, MD [2]

Fat embolism syndrome (FES) is the presence of fat globules in the circulation post traumatic insult which can lodge into the small sized capillaries in the lung, brain and skin leading to devastating clinical manifestations. The two widely accepted theories which explain the pathophysiology of FES are mechanical and biochemical theory. The mechanical theory proposes that there is mechanical obstruction by fat cells from the bone marrow in the end-capillaries after trauma. Biochemical theory attributes the clinical manifestations of FES to the pro inflammatory effect of fat emboli.

Two major theories have been described to explain the pathophysiology of fat embolism syndrome(FES):^[1][2]

• Mechanical theory
• Biochemical theory

The theory proposes that there is mechanical obstruction by fat cells from the bone marrow in the end-capillaries after trauma.

• Post traumatic insult, the fat cells travel via venous sinusoids to the capillaries.
• These cells have potent prothrombotic and proinflammatory potential.
• They trigger rapid aggregation of platelets and accelerated fibrin generation as they travel through the venous system, eventually lodging in the pulmonary arterial circulation.
• Pulmonary capillary obstruction leads to interstitial hemorrhage and edema, alveolar collapse, and reactive hypoxemic vasoconstriction.
• Massive fat emboli may also lead to macrovascular obstruction and shock.
• Fat cells may also enter the arterial circulation via a patent foramen ovale or directly through the pulmonary capillary bed, causing the characteristic neurological and dermatologic findings of FES.

This theory attributes the clinical manifestations of FES to the pro inflammatory effect of fat emboli.^[3][4][5]

• Tissue lipases break down the fat in the bone marrow, forming high levels of the following toxic intermediaries:^[6][7]
  • Free fatty acids:

Free fatty acids are released into the circulation after hydrolysis and deposit into the end capillaries of the lung, manifesting as acute respiratory distress syndrome.^[8][9]

• Cytokines:

Patients with FES are also found to have high levels of certain cytokines such as tumor necrosis factor alpha, phospholipase A2, interleukin 1 and 6.^[10][11]

• C-reactive proteins:

The elevation in c-reactive proteins is responsible for lipid agglutintion in FES which results in microvasculature obstruction and stagnant blood flow.

• Eventually, these intermediate products lead to end-organ dysfunction.
• In the lung, toxic injury to pneumocytes and pulmonary endothelial cells causes vasogenic and cytotoxic edema as well as hemorrhage.
• Acute lung injury or acute respiratory distress syndrome results from damaged pulmonary endothelium that triggers a proinflammatory cytokine cascade.

Following pathological sequence of events occur after an orthopedic trauma such as long bone fracture.

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• There is no genetic association of FES.

There is no characteristic gross pathology associated with fat embolism.

Hematoxylin and eosin staining shows the following changes in the lungs, kidneys and brain:^[12]

Lung:

• Alveolar haemorrhagic edema
• Fat droplet deposition
• Fibrin thrombi
• Multiple fat droplets

Immunohistochemical staining shows the following changes:

• Raised levels of iNOS in the alveolar macrophages.

Kidney:

• Hematoxylin and eosin staining shows fat deposits in the glomeruli.

Brain:

• Fat droplets are seen in vessels.