Hypolipoproteinemia pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamed Moubarak, M.D. [2]
Overview
Multiple mechanisms have been described in different diseases and clinical conditions that are found to be associated with hypolipidemia. Secondary causes are far more common than primary causes and include anemia, hyperthyroidism, critical illness, malignancy, malabsorption, infection, Chronic liver disease, and Chronic inflammation.
Pathophysiology
Primary Lipoprotein Disorders
Shown below is a table summarizing the primary hypolipoproteinemia along with the involved gene and main lipoprotein.
| Primary Hypolipoproteienmia | Gene | Main Lipoprotein Involved |
|---|---|---|
| Abetalipoproteienmia | Microsomal triglyceride transfer protein (MTR) | LDL |
| Apolipoprotein 1 deficiency | Apolipoprotein AI | HDL |
| Chylomicron retention disease | SAR1B | Multiple |
| Familial combined hypolipidemia | ANGPTL3 | Multiple |
| Familial hypoalphalipoproteinemia | ||
| Hypobetalipoproteinemia | Apo B | LDL |
| LCAT deficiency | LCAT | HDL |
| PCSK9 deficiency | PCSK9 | LDL |
| Tangier disease | ABCA1 | HDL |
| Type A Niemann-Pick disease | SMPD1 | HDL |
| Type B Niemann-Pick disease | SMPD1 | HDL |
| Type C Niemann-Pick disease | NPC1 | HDL |
Secondary Lipoprotein Disorders
Hypolipedemia has been found in association with different clinical conditions.
- Anemia: Hypolipedemia has been identified in association with different types of anemia e.g.congenital dyserythropoietic anemia, congenital spherocytosis, sickle cell anemia, beta-thalassemia, aplastic anemia, and sideroblastic anemia.[1][2][3][4][5] The exact etiology of hypolipidemia in anemic patients is not known, some studies outlined different mechanisms,[6][5] another study suggest that hypolipidemia might be the cause rather than the consequence of anemia, which is explained by that cholesterol deficiency leads to rigidity of the erythrocytes, making them more prone to destruction.[7]
- Hyperthyroidism: Thyroid hormone influence lipid metabolism and are common in dyslipidemic patients, and its dysfunction affect composition and transport of lipoproteins,[8] hence the importance of Biochemical screening for thyroid dysfunction in all dyslipidemic patients.
- Critical illness: Cholesterol levels drop at the onset of acute illness, and normalize after recovery. This may predispose the critically ill patient to sepsis and adrenal failure, and early enteral nutrition and tight glycemic control recommended to accelerate the recovery of the cholesterol levels.[9][10]
- Malignancy: Several epidemiological studies suggested an inverse relation between serum cholesterol level and cancer mortality.[11]
- Malabsorption: Fat malabsorption can lead to hypolipidemia, as the dietary fats constitute the exogenous source of body lipids. Brar et al demonstrated that celiac disease is associated with hypocholesterolemia and a gluten-free diet will result in rising of total cholesterol and HDL.[12]
- Infection: The chronic effect of proinflammatory cytokines on lipoprotein metabolism seen in acute and chronic, bacterial, viral, and parasitic infections all might induce hypocholesterolemia.[13]
- Chronic liver disease: Hypolipidemia is frequently observed in severe chronic hepatic insufficiency, as the hepatocytes is the main site for lipid metabolism.[14]
- Chronic inflammation: In the acute phase response to inflammation, reduction in plasma lipid levels is a well known phenomenon, it is explained by the chronic effect of proinflammatory cytokines on lipoprotein metabolism.[15][16]
References
- ↑ Shalev H, Kapelushnik J, Moser A, Knobler H, Tamary H (2007). "Hypocholesterolemia in chronic anemias with increased erythropoietic activity". Am J Hematol. 82 (3): 199–202. doi:10.1002/ajh.20804. PMID 17039515.
- ↑ Johnsson R, Saris NE (1981). "Plasma and erythrocyte lipids in hereditary spherocytosis". Clin Chim Acta. 114 (2–3): 263–8. PMID 7285349.
- ↑ Shores J, Peterson J, VanderJagt D, Glew RH (2003). "Reduced cholesterol levels in African-American adults with sickle cell disease". J Natl Med Assoc. 95 (9): 813–7. PMC 2594470. PMID 14527048.
- ↑ Hartman C, Tamary H, Tamir A, Shabad E, Levine C, Koren A; et al. (2002). "Hypocholesterolemia in children and adolescents with beta-thalassemia intermedia". J Pediatr. 141 (4): 543–7. doi:10.1067/mpd.2002.127498. PMID 12378195.
- ↑ 5.0 5.1 Yokoyama M, Suto Y, Sato H, Arai K, Waga S, Kitazawa J; et al. (2000). "Low serum lipids suggest severe bone marrow failure in children with aplastic anemia". Pediatr Int. 42 (6): 613–9. PMID 11192516.
- ↑ Asai K, Kuzuya M, Naito M, Funaki C, Kuzuya F (1988). "Effects of splenectomy on serum lipids and experimental atherosclerosis". Angiology. 39 (6): 497–504. PMID 3377269.
- ↑ Pok SJ, Deutsch E, Nemesánszky E, Sas G, Pálos LA, Bräuer H; et al. (1980). "[Cholesterol deficiency. A pathogenetic factor in chronic anemias? Preliminary report of a study in three states (author's transl)]". MMW Munch Med Wochenschr. 122 Suppl 3: S123–31. PMID 6779152.
- ↑ Liberopoulos EN, Elisaf MS (2002). "Dyslipidemia in patients with thyroid disorders". Hormones (Athens). 1 (4): 218–23. PMID 17018450.
- ↑ Marik PE (2006). "Dyslipidemia in the critically ill". Crit Care Clin. 22 (1): 151–9, viii. doi:10.1016/j.ccc.2005.08.008. PMID 16399025.
- ↑ Dunham CM, Fealk MH, Sever WE (2003). "Following severe injury, hypocholesterolemia improves with convalescence but persists with organ failure or onset of infection". Crit Care. 7 (6): R145–53. doi:10.1186/cc2382. PMC 374375. PMID 14624689.
- ↑ Tomiki Y, Suda S, Tanaka M, Okuzawa A, Matsuda M, Ishibiki Y; et al. (2004). "Reduced low-density-lipoprotein cholesterol causing low serum cholesterol levels in gastrointestinal cancer: a case control study". J Exp Clin Cancer Res. 23 (2): 233–40. PMID 15354407.
- ↑ Brar P, Kwon GY, Holleran S, Bai D, Tall AR, Ramakrishnan R; et al. (2006). "Change in lipid profile in celiac disease: beneficial effect of gluten-free diet". Am J Med. 119 (9): 786–90. doi:10.1016/j.amjmed.2005.12.025. PMID 16945614.
- ↑ Bentz MH, Magnette J (1998). "[Hypocholesterolemia during the acute phase of an inflammatory reaction of infectious origin. 120 cases]". Rev Med Interne. 19 (3): 168–72. PMID 9775136.
- ↑ D'Arienzo A, Manguso F, Scaglione G, Vicinanza G, Bennato R, Mazzacca G (1998). "Prognostic value of progressive decrease in serum cholesterol in predicting survival in Child-Pugh C viral cirrhosis". Scand J Gastroenterol. 33 (11): 1213–8. PMID 9867102.
- ↑ Elmehdawi R (2008). "Hypolipidemia: a word of caution". Libyan J Med. 3 (2): 84–90. doi:10.4176/071221. PMC 3074286. PMID 21499464.
- ↑ Ettinger WH, Sun WH, Binkley N, Kouba E, Ershler W (1995). "Interleukin-6 causes hypocholesterolemia in middle-aged and old rhesus monkeys". J Gerontol A Biol Sci Med Sci. 50 (3): M137–40. PMID 7743398.