Hypolipoproteinemia pathophysiology: Difference between revisions
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Template:Hypolipidemia 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 hypolipidemia
Genetic mutations cause an underproduction or increased clearance of Low Density Lipoproteins (LDL) and result in lipid levels low enough to cause significant consequences.
- Abetalipoproteinemia (Bassen-Kornzweig syndrome): is a rare autosomal recessive disorder that interferes with the normal absorption of fat and fat-soluble vitamins from food. It is caused by a mutation in microsomal triglyceride transfer protein, resulting in deficiencies in the apolipoproteins B-48 and B-100, which are critical to chylomicron and very-low-density lipoprotein (VLDL) formation.[1] Dietary fat cannot be absorbed, and lipoproteins in both metabolic pathways are virtually absent from serum, TC is typically < 45 mg/dL (< 1.16 mmol/L), TGs are < 20 mg/dL (< 0.23 mmol/L), and LDL is undetectable. The condition is often first noticed in infants with fat malabsorption, steatorrhea, and failure to thrive.
- Hypobetalipoproteinemia: is an autosomal dominant disorder, defined as below 5th percentile LDL-cholesterol or apolipoprotein (apo) B in the plasma. Subjects are generally heterozygous and asymptomatic except for TC < 120 mg/dL and LDL cholesterol < 80 mg/dL, TGs are normal. Homozygous patients have lower lipid levels (TC < 80 mg/dL, LDL cholesterol < 20 mg/dL), or absent apo B synthesis, leading to symptoms and signs of abetalipoproteinemia.[2]
- Chylomicron retention disease: is a very rare autosomal recessive condition caused by an unknown mutation leading to deficient apo B secretion from enterocytes. Chylomicron synthesis is absent, but VLDL synthesis remains intact.
Secondary hypolipidemia
- In anemia:
Mechanisms suggested that high-erythropoitic activity-associated hypocholesterolemia is due to increased cholesterol requirements by the proliferating erythoid cells.[3]
- In hyperthyroidism:
Thyroid hormone dysfunction affect composition and transport of lipoproteins,[4] Moreover, the triiodothyronine (T3) enhances the gene expression of the LDL receptor and hence the receptor activity.[4]
- In critical illness:
Downregulation of hepatic synthesis due to decreased production of cholesterol precursors particularly lanosterol and lathosterol.[5][6] Other different mechanisms include loss of apoproteins in burns, increased cholesterol catabolism, and Low cholesterol concentrations associated with high levels of cytokines such as interleukin (IL)-6 and IL-10 may be involved.[7][6][8]
- In malignancy:
Elevated LDL receptor activity in malignant cells may be a contributing factor to hypocholesterolemia in some cancer patients.[9]
- In malabsorption:
The loss of the main source of exogenous fat can lead to hypolipidemia.[10]
- In infection:
The chronic effect of proinflammatory cytokines on lipoprotein metabolism, which is mediated by different cytokines as IL-1 and tumor necrosis factor-alpha (TNF) which are involved in the acute phase response during sepsis.[11] It has been observed that Convalescing patients ready discharge have improved cholesterol levels, whereas dying patients appear to have progressive hypocholesterolemia.[12]
- In Chronic liver disease:
Isolated deficiency of apolipoprotein B indicates abetalipoproteinemia or familial hypobetalipoproteinemia, which can result in liver involvement in the form of elevated transaminases, fatty liver and cirrhosis. While deficiency of both apolipoprotein A and apolipoprotein B is a manifestation of advanced chronic liver disease.[13]
- In Chronic inflammation:
Hypolipedemia occur in chronic inflamation due to the chronic effect of proinflammatory cytokines on lipoprotein metabolism. Ettinger et al demonstrated that chronic IL-6 injection causes acquired hypocholesterolemia in nonhuman primates.[14]
References
- ↑ Benayoun L, Granot E, Rizel L, Allon-Shalev S, Behar DM, Ben-Yosef T (2007). "Abetalipoproteinemia in Israel: evidence for a founder mutation in the Ashkenazi Jewish population and a contiguous gene deletion in an Arab patient". Mol Genet Metab. 90 (4): 453–7. doi:10.1016/j.ymgme.2006.12.010. PMID 17275380.
- ↑ Schonfeld G, Lin X, Yue P (2005). "Familial hypobetalipoproteinemia: genetics and metabolism". Cell Mol Life Sci. 62 (12): 1372–8. doi:10.1007/s00018-005-4473-0. PMID 15818469.
- ↑ 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.
- ↑ 4.0 4.1 Liberopoulos EN, Elisaf MS (2002). "Dyslipidemia in patients with thyroid disorders". Hormones (Athens). 1 (4): 218–23. PMID 17018450.
- ↑ Bakalar B, Hyspler R, Pachl J, Zadak Z (2003). "Changes in cholesterol and its precursors during the first days after major trauma". Wien Klin Wochenschr. 115 (21–22): 775–9. PMID 14743581.
- ↑ 6.0 6.1 Giovannini I, Boldrini G, Chiarla C, Giuliante F, Vellone M, Nuzzo G (1999). "Pathophysiologic correlates of hypocholesterolemia in critically ill surgical patients". Intensive Care Med. 25 (7): 748–51. PMID 10470581.
- ↑ Coombes EJ, Shakespeare PG, Batstone GF (1980). "Lipoprotein changes after burn injury in man". J Trauma. 20 (11): 971–5. PMID 7431454.
- ↑ Bonville DA, Parker TS, Levine DM, Gordon BR, Hydo LJ, Eachempati SR; et al. (2004). "The relationships of hypocholesterolemia to cytokine concentrations and mortality in critically ill patients with systemic inflammatory response syndrome". Surg Infect (Larchmt). 5 (1): 39–49. doi:10.1089/109629604773860291. PMID 15142422.
- ↑ Peterson C, Vitols S, Rudling M, Blomgren H, Edsmyr F, Skoog L (1985). "Hypocholesterolemia in cancer patients may be caused by elevated LDL receptor activities in malignant cells". Med Oncol Tumor Pharmacother. 2 (3): 143–7. PMID 4068801.
- ↑ 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.
- ↑ 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.
- ↑ Shah SS, Desai HG (2001). "Apolipoprotein deficiency and chronic liver disease". J Assoc Physicians India. 49: 274–8. PMID 11225145.
- ↑ 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.