**10. Biochemical hypothesis**

In 1927, Lehman and Moore first postulated that a substance exists that causes destabilization of the emulsion of chylomicrons in the bloodstream with coalescence of fat

Taviloglu & Yanar, 2007)

2002; Robert et al., 1993; Weinhouse, January 2011)

1993)

2000)

(Bulger et al., 1997; Haber et al., 1988; Jenkins et al., 2002; Kitchell & Balogh, 1986; Rayburg et al., 2010; Ritter et al., 1997; Robert et al.,

Cyclosporine A solvent (Weinhouse, January 2011)

Carbon tetrachloride poisoning (Macmahon & Weiss, 1929;

Intraosseous fluid and drug administration (Hasan et al., 2001; Vichinsky et al.,

In view of the large number of patients who are treated with liposome-embedded drugs, reports of fatal FE caused by intravenous liposome drug delivery or intra-venous

Pathophysiology of FES remains unknown. Two main theories, namely mechanical and biochemical, dominate the literature and have gained acceptance (Bulger et al., 1997; Choi et

Gauss first proposed the mechanical theory of fat embolization which requires that large fat cells in the bone marrow rupture into the venous circulation through torn venules at the fracture site in the setting of a favorable pressure gradient (increased intra-medullary pressure). These fat globules subsequently embolize to the lungs and obstruct the pulmonary capillaries (Gauss, 1924). Systemic embolization takes place via intra-cardiac shunts or PFO. Small fat droplets (7-10 micrometers) can pass through pulmonary capillaries (Parisi et al., 2002) causing systemic embolization in the absence of anatomic shunt. The clinical picture is dictated by the extent of the organ(s) involved. However,

• "Latent period": from the time of onset of injury to the onset of symptoms and signs of

Therefore factors other than mechanical obstruction must be playing a role which led to the

In 1927, Lehman and Moore first postulated that a substance exists that causes destabilization of the emulsion of chylomicrons in the bloodstream with coalescence of fat

hyperalimentation are debatable (Kitchell & Balogh, 1986; Tolentino et al., 2004).

Corticosteroids (Bulger et al., 1997; Jenkins et al.,

**8. Drugs associated with fat embolization (Table-4)** 

Infusion of lipids at a rate greater than normal

al., 2002; Mellor & Soni, 2001; Parisi et al., 2002).

mechanical theory does not explain the following observations:

• Not all patients who have fat emboli develop FES (Aoki et al., 1998)

clearing capacity, i.e. 3.8 gm/kg/day,

Table 4. Drugs related

**9. Mechanical hypothesis** 

• Non-Traumatic causes of FES

**10. Biochemical hypothesis** 

biochemical hypothesis.

FES

stores in response to stress and catecholamine release (Lehman & Moore, 1927). Currently the most widely held view is that there is physiochemical alteration leading to degradation of embolized fat and production of toxic intermediates—mainly Free Fatty Acids (FFAs). Circulating FFAs originating from triglycerides at the fracture site may become concentrated as a result of systemic lipolysis induced by catecholamines. Alternatively, fat emboli trapped in pulmonary vessels may be metabolized to FFAs and glycerol by lipase secreted by lung parenchymal cells (P. L. Baker et al., 1971). However the exact source of FFAs remains unknown. Regardless of the source of the FFAs, circulating FFAs level is elevated in patients with fractures and in animal models of nontraumatic fat embolism. It has been postulated that decreased hepatic clearance as in shock, sepsis, or decreased plasma concentration of albumin also increase the risk of FES ( Mays, 1970; Moylan et al., 1976). FFAs have been shown in both animal and human studies to have the following systemic effects

	- capillary leak
	- curtailed surfactant production
	- interstitial hemorrhage and pulmonary edema (Herndon, 1975; Parker et al., 1974; Szabo et al., 1977)

Coagulation cascade activation, disseminated intravascular coagulation (DIC), and antifibrinolytic pathways may further contribute to lung injury (E. G. King et al., 1971; Saldeen, 1970).The biochemical theory, could explain "latent period" and nontraumatic forms of FES (Schnaid et al., 1987). It must be emphasized that evidence is largely circumstantial and the exact pathophysiologic mechanism responsible for FES remains unknown.
