Introduction:
Hypertriglyceridemia with rising serum triglyceride levels, acute pancreatitis risk, and severity rise is an unusual but well-established cause of acute pancreatitis associated with high morbidity and death. Therefore, it is essential to determine that hypertriglyceridemia is causing pancreatitis and start the proper course of treatment. The first supportive care is comparable to managing other acute pancreatitis causes with additional targeted medications designed to reduce serum triglyceride levels. This comprises heparin infusion, insulin, hemofiltration, and plasmapheresis. After the acute episode, hypolipidemic medications should be started with dietary and lifestyle changes to stop future attacks.
The two most frequent causes of acute pancreatitis are gallstones and excessive alcohol consumption (AP). With a reported prevalence of 2 to 4 %, hypertriglyceridemia is a rare but well-established cause of acute pancreatitis. Triglyceride (TG) levels are classified by the National Cholesterol Education Program ATP III as
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Normal (150 mg/dL).
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Borderline high (150 to 199 mg/dL).
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High (200 to 499 mg/dL).
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Very high (>500 mg/dL) (1 mmol = 88.5736 mg/dL).
TG levels above 1000 mg/dL have typically been linked to AP, but the exact threshold varies and varies from person to person.
What Is the Etiology of Hypertriglyceridemia?
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Primary and secondary are the two main types of hypertriglyceridemia (HTG) etiology. However, the major factor that makes HTG more severe by the interaction of the primary and secondary variables.
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In the genomic era, Fredrickson Type I, IV, and V, familial chylomicronemia syndrome (FCS), primary hypertriglyceridemia, and mixed hypertriglyceridemia were the conditions most frequently associated with severe hypertriglyceridemia. While primary hypertriglyceridemia (IV) manifests in adulthood and is typically brought on by a secondary source, FCS (I) and mixed hypertriglyceridemia (V) cause more severe hypertriglyceridemia and frequently occur early.
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Along with mutations in GPIHBP1 (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1), LMF1(lipase maturation factor1), and other genes involved in lipoprotein synthesis and metabolism, common genetic defects causing severe hypertriglyceridemia to include lipoprotein lipase deficiency, LPL gene mutation, and apolipoprotein C II deficiency. While mild to moderate HTG is likely to have polygenic inheritance, severe hypertriglyceridemia is more likely to have a monogenic pattern. According to several research, individuals with HTG-AP frequently have one or more secondary causes.
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Obesity, alcohol misuse, uncontrolled diabetes mellitus, hypothyroidism, chronic renal failure, and medications, including estrogen, corticosteroids, and retinoids, are secondary variables linked to HTG.
What Is The Pathophysiology behind Hypertriglyceridemia?
It is still being determined how hypertriglyceridemia causes AP with absolute certainty. Most recognized hypotheses are based on animal models that explain how excessive TGs are converted by pancreatic lipase to free fatty acids (FFA), which causes damage and ischemia to pancreatic cells. It has also been suggested that increased TGs in pancreatic capillaries cause hyperviscosity, which causes ischemia; however, it is unclear why this ischemia exclusively affects the pancreas and not other organs. HTG-AP has been linked to certain genetic alterations, such as CFTR and ApoE gene variants. HTG-induced AP is likely the consequence of intricate interactions between several variables, each contributing differently to each patient. The precise pathophysiology of HTG-AP has to be clarified by more studies.
Hyperlipidemia is widely documented to play a role in acute pancreatitis as a precipitant and an epiphenomenon. Coexisting medical disorders like diabetes should prompt further investigation. Less than 5 % of cases of hypertriglyceridemia have genetic causes, and the condition is more frequently secondary to conditions like diabetes, obesity, pregnancy, excessive carbohydrate consumption, hypothyroidism, alcoholism, hepatitis, sepsis, renal failure, and medications like thiazide, tamoxifen, cyclosporine protease inhibitors, and isotretinoin.
What Are Chylomicrons And How Does It Cause Pancreatitis?
Triglyceride-rich lipoprotein particles are known as chylomicrons. They circulate in the blood when triglycerides exceed ten mmol/l (900 mg/dl). These are big enough to block the pancreatic capillaries, causing ischemia, a structural change in the acinar tissue, and the release of pancreatic lipase. Increased concentrations of free fatty acids brought on by enhanced lipolysis trigger the production of inflammatory mediators and free radicals, which result in inflammation, edema, and necrosis. After quitting the hyperlipidemic medication four times, our patient developed pancreatitis (four episodes altogether; triglycerides > 900 mg/dl each time). The result of dietary fat absorption is chylomicrons.
What Is The Management of Hyperlipidemia?
Non-Pharmacological: Non-pharmacological strategies include
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Losing weight.
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Consuming fewer calories, fats.
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Processed carbohydrates.
Pharmacological: Fibrates are the cornerstone of treatment; they improve HDL cholesterol by 20 percent while lowering plasma triglyceride levels by up to 50 percent. They affect the liver's PPARs (peroxisome proliferator-activated receptors), which results in enhanced lipolysis of plasma triglycerides and reduced VLDL production from the liver. Additionally, they raise HDL and lower tiny dense LDL particles by blocking hydroxyl-methylglutaryl CoA reductase. Statins lower cholesterol, which lowers the risk of coronary heart disease in people with type 2 diabetes.
Niacin is recommended as an adjuvant treatment with fibrates for patients with severe HTG (TGs > 500 mg/dL). All antihyperlipidemic medications except Fibrates are effective at lowering TG levels. Myopathy, cholelithiasis, and reversible creatinine elevation are typical side effects of fibrates.
Insulin and Heparin: Insulin stimulates lipoprotein lipase (LPL) activity, which speeds up the breakdown of chylomicrons and lowers TG levels. Additionally, insulin will give the pancreatic tissue a break, and by increasing the expression of the human leukocyte antigen on monocytes and lowering cell apoptosis, it may help with immunoparalysis. In two to three days, insulin reduces TGs levels by 50 to 75 %. Heparin causes the endothelium cell to release stored lipoprotein lipase, which lowers TGs levels. In case reports and case series, a combination of insulin and heparin has been used to reduce TGs levels, with a mean drop in TGs levels by 50 % within 24 hours. Rebound hypertriglyceridemia is a worry since continuous or long-term heparin infusion has been demonstrated to deplete LPL, which lowers chylomicron catabolism and raises TG levels.
Plasmapheresis: By swiftly eliminating TGs and chylomicrons from the blood, plasmapheresis (PEX) stops the spread of inflammation and pancreatic damage. Compared to conservative treatment, which often takes several days to achieve the same reduction in TG levels, PEX significantly lowers lipid levels in just a few hours. Most patients only need one PEX session because it is said to reduce TG levels by 50 to 80 %.
Conclusion:
Compared to other causes, HTG is more frequently linked to severe pancreatitis, although no difference in mortality has been noted. According to many studies, the severity of acute pancreatitis is related to the degree of triglyceride rise. However, additional elements, including pancreatic lipase activity, the effectiveness of fatty acid (FA) removal from the serum, and the gravity of the underlying pancreatic damage, are likely to impact the severity of acute pancreatitis.
