Hypertriglyceridemia-Rare Etiological Condition of Necrotic- Hemorrhagic Pancreatitis

CRISTINA SERBAN1,2, MIHAELA DEBITA1*, AUREL NECHITA4,5, DRAGOS VOICU2*, MIHAELA DUMITRU3, LAURA REBEGEA3,4, DOREL FIRESCU1,2 1Sf. Ap. Andrei Emergency Clinical Hospital, Surgery Clinic II, 177 Brailei Str., 800366, Galati, Romania 2Dunarea de Jos University of Galati, Faculty of Medicine, Surgical Clinical Department, 47 Domneasca Str., 800008, Galati, Romania 3Sf. Ap. Andrei Emergency Clinical Hospital, Department of Radiotherapy, 177 Brailei Str., 800366, Galati, Romania 4Dunarea de Jos University of Galati, Faculty of Medicine, Medical Clinical Department, 47 Domneasca Str., 800008, Galati, Romania 5Sf.Ioan Emergency Clinical Hospital for Children, Pediatric Clinic II, 2 Ghe. Asachi Str., 800494, Galati, Romania

Acute pancreatitis induced by hypertriglyceridemia was found in 1.3-3.8% of patients [1]. Hypertriglyceridemia is the most common etiology after alcohol consumption and gallstones [1,2]. The risk of acute pancreatitis is of approximately 5% at triglyceride levels above 1000 mg / dL and of 10% -20% at values higher than 2000 mg / dL [4]. The pathophysiological mechanisms include hydrolysis of triglycerides by pancreatic lipase, excessive formation of free fatty acids, secondary inflammatory changes and capillary lesions [3][4][5][6][7]. The hyper-viscosity of the blood with tissue's ischemia plays an additional role.
We present a rare pathological situation of a young patient of 24 years old with acute necrotic-hemorrhagic pancreatitis induced by hypertriglyceridemia.

Experimental part Material and method
A 24-year-old patient with newly discovered insulinrequiring type II diabetes is transferred from the Internal Medicine Department to the Surgery Clinic IIof Sf. Apostol Andrei Emergency Hospital, Galati, with the diagnosis of acute pancreatitis.
The abdominal and pelvic CT with contrast agent had revealed left pleural effusion with a liquid blade with maximum thickness of 26 mm, right pleural effusion with a liquid blade with maximum thickness of 22 mm, pancreas with increased dimensions, low contrast agent capture, infiltrated aspect of peripancreatic tissues, inaccurate fluid clusters delimited in the bilateral peritoneal and retroperitoneal cavity, infiltrated aspect of bilateral lumbar muscle planes.

Results and discussions
Surgery was performed, with the diagnosis of severe acute pancreatitis induced by hypertriglyceridemia and necrotic-hemorrhagic pancreatitis, enzyme peritonitis, hepatomegaly, chronic alithiasis cholecystitis has been reported. Capsulotomy, necrectomy, lavage, multiple peritoneal drainage were performed.
The post surgery evolution was unfavorable, ending with the patient's death 3 days after surgery.
The microscopic examination described the epiploic fragment (6320 / 29.11.2017) with necrosis areas, where the adipocytes lose nuclei, retaining only the contour of the cell membranes, the cytoplasm being replaced by a granular, eosinophilic, opaque sediment, with areas more basophilic, occurred through the fat's hydrolysis followed by the precipitation of calcium salts. Moderate acute granulocytic inflammatory infiltration and diffuse hematic infiltration were also found. The histopathological aspects correspond to the changes from cytosteatonecrosis.
The extracted pancreatic tissue (6321 / 29.11.2017) was composed of completely necrotic tissue fragments with rich acute granulocyte infiltration and fibrin deposits.
The pathogenic mechanism of how HTG can cause acute pancreatitis remains unclear and controversial. Several theories have been suggested, most frequently referring to the excess of triglycerides that are hydrolyzed by pancreatic lipase, and free fatty acids (FFAs) are formed in high concentrations [8][9][10][11][12].
FFA overloads the ability of attachment of albumin and of the self-aggregate to the micellar structures with detergent properties [13][14][15][16]. Thus, acinar cell lesion and pancreatic capillary lesion are formed. The resulting ischemia creates an acidic environment that further enhances the FFA toxicity [17][18][19]. Another underlying physiopathologic principle may be hyperviscosity due to high levels of chylomicrons. The hyperviscosity due to hyperchylomicronemia is believed to evolve to ischemia and acidosis in the pancreatic capillaries. In addition, there is evidence that FFA affects the endothelium and thus acute pancreatitis may be associated with microtrombosis and subsequent ischemia [20,21]. The stress of the endoplasmic reticulum would also be involved in the HTGP mechanism [22]. There are also reports on specific genes associated with HTGP. A Chinese study reported a CFTR mutation and a TNF promoter polymorphism, which were independent risk factors for HTGP. CFTR gene's mutation rates in HTG with and without acute pancreatitis were 26.1% (12 of 46) and 1.3% (one out of 80) [22], respectively. Another recent Spanish study finds that the e4 allele of the APOE gene is more common in patients with HTGP [23,24]. It is likely that all the theories described contribute to the development of HTGP to a certain degree. However, additional research efforts in this area will be needed to shed more light on HTGP pathophysiology.
Hypertriglyceridemia is also an independent risk factor for acute renal lesions [24]. This hypothesis refers to the action of pancreatic enzymes on the triglycerides accumulated in the kidneys, which may explain acute renal lesions in the early stage of the disease [25][26][27][28][29][30][31][32][33].
Interestingly, beyond the apparent significance of a triglyceride threshold for the initialization of acute pancreatitis, its stringency does not seem to correlate directly with triglyceride levels. Although the patient is under treatment, the clinician should investigate the etiology of hypertriglyceridemia by verifying the effects of the patient's chronic medication, of his/her medical history or of his/her family members in his/her search for familial hyperlipidemias.

Conclusions
Acute pancreatitis induced by hypertriglyceridemia remains still a Pandora's box with surprising types of patients.
A severe, fatal acute pancreatitis may complicate an asymptomatic, undiagnosed hypertriglyceridemia.
Various diagnostic methods can be very useful in determining the cause of the pancreatic inflammation, but nevertheless, the most valuable approach remains a detailed anamnesis and the clinical examination.