• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-.

Cover of Madame Curie Bioscience Database

Madame Curie Bioscience Database [Internet].

Show details

Hyperemesis Gravidarum and Maternal Liver Disease

, , and *.

* Corresponding Author: Section on Gastroenterology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, 27157 U.S.A. Email: kkoch@wfubmc.edu

Figure 1. Spectrum of nausea and vomiting of pregnancy.

Figure 1

Spectrum of nausea and vomiting of pregnancy. Over 50% of patients with NVP experience mild nausea alone, while nearly 45% have moderate nausea with or without vomiting. While HG represents the most severe form of pathology within NVP, it comprises no (more...)

Hyperemesis gravidarum (HG) is the most severe form of illness within the spectrum of nausea and vomiting of pregnancy (NVP). HG affects millions of pregnant women annually, imparts significant cost to society, and places mother and her unborn child at risk. The nausea and vomiting characteristic of HG presents early in pregnancy and usually terminates by the 20th gestational week. Liver disease, usually consisting of mild serum transaminase elevation, occurs in almost 50% of patients with HG. While multiple risk factors have been proposed, the etiology of HG and the maternal liver disease seen in HG remains unclear. Current investigations underscore the potential roles of starvation injury, placental release of inflammatory cytokines, and impairment of fatty acid oxidation in the pathogenesis of the maternal liver disease observed in HG.

“Let me speak the plain truth—my sufferings are very great—my nights indescribable —sickness with scarce a reprieve—I strain until what I vomit is mixed with blood.” Charlotte Bronte, author of Jane Eyre, purported to have died from hyperemesis gravidarum.

NVP is a common entity which affects up to 90% of pregnancies.1 The breadth of disease in NVP is considerable. Pathology can range from mild nausea to HG which is marked by unrelenting nausea and vomiting causing dehydration, metabolic derangements, and nutritional deficiencies. The spectrum of NVP is illustrated in Figure 1.

Nausea and Vomiting of Pregnancy

NVP affects the great majority of pregnancies. Over 4 million women suffer with NVP each year and the condition results annually in approximately 8.6 million lost hours of paid employment and 5.8 million lost hours of household work.2 NVP typically consists of mild nausea and vomiting presenting during the first trimester of pregnancy. Physical examination and laboratory findings in most patients with NVP are within normal limits. NVP is more common in young, nulliparous, and obese women while maternal age greater than 35 years and cigarette smoking may confer protective effects.3 NVP is frequently seen in Western countries and is relatively rare in African and Asian populations.

NVP is a diagnosis of exclusion and the differential diagnosis of nausea in pregnancy is vast. Mechanical obstruction, peptic and biliary disease, hormonal and metabolic imbalances, medication effects, and central nervous systems disorders must all be ruled out before one makes the diagnosis. Once the diagnosis of NVP is certain, supportive care including dietary modifications with small and frequent meals abundant in protein as well as pharmacologic therapy with phenothiazine antiemetics treat most cases of NVP successfully.

The etiology of NVP remains uncertain, although numerous hypotheses have been proposed. Backed by the study of Fairweather et al in 1968, hysteria and other psychological factors were for many years believed to be largely responsible for NVP.4,5 Subsequent studies, however, have not corroborated these findings. The association between NVP and esophageal and gastric dysmotility was first reported over 20 years ago. Recent studies have confirmed the association between gastric dysrhythmias and NVP and treatment of women in their first-trimester of pregnancy with high-protein meals decreased their nausea and gastric dysrhythmias.6,7 The mechanisms of both the gastric dysrhythmias and the beneficial effects of protein meals are unknown. The proposal of hormones such as human chorionic gonadotropin (hCG), estrogen, and progesterone as etiologic agents in NVP is underscored by their rapid degree of elevation during the early phases of pregnancy. Unfortunately, multiple studies measuring hormonal levels of hCG, estrogen and progesterone in patients with NVP have yielded inconsistent results.8Helicobacter pylori (H. pylori) has received much recent press as a potential cause of NVP based on the findings of a study conducted in Taiwan which reported correlation between seropositivity for H. pylori infection and the presence of NVP.9 The role of H. pylori in NVP is not well supported by the data, however, as seropositivity for infection did not correspond with the gastrointestinal symptoms of NVP.

Hyperemesis Gravidarum

HG is most severe form of NVP and affects a small but significant portion of pregnancies. HG, which occurs in approximately 1 out of every 200 pregnancies, is commonly defined as persistent first trimester vomiting that leads to weight loss in excess of 5% prepregnancy body weight as well as to ketonuria unrelated to other causes. Patients with HG are typically ill-appearing and show clinical signs of dehydration including poor skin turgor and dry mucous membranes. Jaundice is uncommon, but indicates liver involvement when present. Common laboratory derangements seen in HG include hypokalemia, hyponatremia, metabolic alkalosis, and polycythemia. Abnormal liver function tests, as discussed below, are common in patients with HG.

While HG is felt to share similar risk factors and pathogenesis with NVP as a whole, multiple gestations, molar pregnancies and fetal anomalies such as hydrops fetalis and trisomy 21 appear to impart particular risk for the development of HG.10,11 In contrast to most patients with NVP, hospitalization for intravenous fluids, intravenous antiemetics, and bowel rest is often required in HG. Although the effects of mild cases of NVP on mother and fetus is debated, the severe vomiting and malnourishment seen in HG appears to confer poor pregnancy outcomes such as preterm labor and hemorrhage, fetal malformations, and low birth weight.12

Liver Disease in Hyperemesis Gravidarum

Maternal liver disease occurs in nearly 50% of patients who require hospitalization for HG.13 In one series, HG accounted for 32% of liver function test abnormalities among pregnant women of all gestational ages and was responsible for 94% of liver function test abnormalities seen in pregnant women during their fist trimester of gestation.14 Unfortunately, despite the high incidence of liver disease in HG, clinical methods to predict which patients with HG are at risk for liver involvement are lacking.

Spectrum of Maternal Liver Disease in Hyperemesis Gravidarum

The spectrum of liver disease in HG is broad. With the exception of rare cases of jaundice, the clinical presentation of HG with and without liver involvement is nearly identical. Mild aminotransferase elevation (up to 200 U/l) is the most common liver laboratory abnormality seen in HG, although increased alkaline phosphatase up to twice normal values and mild hyperbilirubinemia (mixed direct and indirect fractions) up to 4 mg/dl may also occur.15 There are rare case reports of aminotransferases elevation greater than 1600 U/l, but fulminant liver failure in HG has not been reported.16,17 The severity of nausea and vomiting in patients with HG and liver disease, as a general rule, correlates with the degree of liver enzyme elevation.18 Imaging studies of the liver in patients with HG are usually unremarkable, although abdominal ultrasounds are always advised in patients with suspected HG in order to rule out gestational trophoblastic disease and multiple gestations. Liver biopsies are rarely necessary in HG and are performed in very few patients. When liver biopsies are done, they may show the histopathologic changes of necrosis, steatosis and bile plugs.15,19 The treatment for HG with liver disease is the same as HG without liver disease and usually entails hospitalization for intravenous fluids, intravenous antiemetics, bowel rest and, rarely, parenteral nutrition. Unlike the other pregnancy-related liver diseases discussed elsewhere in the text, HG with liver involvement is almost never fatal. Liver function abnormalities usually return to normal levels within a few days of volume expansion and the cessation of vomiting. No long-term sequelae of liver dysfunction have been described in patients with pregnancies complicated by HG and liver disease.

Differential Diagnosis of Liver Disease in Hyperemesis Gravidarum

HG with liver disease is a diagnosis of exclusion, and the differential diagnosis of nausea and vomiting in pregnancy with abnormal liver function tests is extensive. Before the diagnosis can be made, disease states unrelated to pregnancy such as gastrointestinal disorders (e.g., viral hepatitis and cholecystitis), metabolic disease (e.g., diabetes and hyperthyroidism), and medication effects, must be ruled out. Other pregnancy-related conditions with nausea, vomiting and liver dysfunction such as the acute fatty liver of pregnancy (AFLP) and the hemolysis elevated liver enzymes and low platelets (HELLP) syndrome typically present in the third trimester of gestation and thus are readily distinguished from HG in most cases.

Pathogenesis

The Starvation Injury Hypothesis

The pathogenesis of liver disease in HG is not well understood. Initial reports by Adams et al in 1968 proposed that starvation injury might be responsible.20 For nearly twenty years, subsequent studies indirectly supported this hypothesis. First, elevated serum aminotransferases and bilirubin were noted in patients with kwashiorkor. Second, diminished bile excretion and bile flow was observed in rat models during fasting states. Third, a temporary elevation in liver enzymes was noted in a cohort of 46 obese patients in the midst of hypocaloric “starvation” diets resulting in rapid weight loss.21,22,23 Morali et al challenged the hypothesis of starvation injury in a retrospective review of the medical records of 80 patients hospitalized for HG between 1976 and 1986. Patients, all of whom had known urinary ketones (used as a starvation surrogate) and liver function tests, were divided into groups with either normal liver enzymes or abnormal liver enzymes. In these two groups of patients, Morali tested the statistical significance between ketonuria and elevated liver function tests and also gauged the relationship between quantitative ketonuria and the degree of liver enzyme elevation. Although ketonuria and elevated liver function tests were significantly associated, there was no correlation between the degree of ketonuria and the magnitude of liver enzyme elevation. This suggests that other factors, in addition to starvation injury, contribute to liver enzyme elevation in patients with HG.24 Placental release of inflammatory cytokines and disorders of fatty acid oxidation may represent some of these factors.

The Placental Cytokine Hypothesis

Cytokines are soluble, low molecular weight proteins secreted by activated macrophages and lymphocytes. Cytokines have multiple biologic functions, including the regulation of immunity and inflammation. In pregnancy, the placenta is inundated with macrophages and lymphocytes and is an important source of many inflammatory cytokines including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α).25-29 Even though cytokines are thought to be an integral part of the placental-maternal unit during normal gestation, over-expression of cytokine-producing cells has long been proposed as a potential cause of numerous pregnancy-associated diseases including preeclampsia and HG. While TNF-α-induced hepatotoxicity in viral hepatitis and alcoholic liver disease is relatively well-characterized, the hepatotoxic role inflammatory cytokines play in other conditions such as pregnancy remains unclear.30 In order to study the role of cytokines in patients with HG, Kaplan et al measured the levels of TNF-α, IL-2, and IL-6 in 30 healthy nonpregnant women, 30 healthy pregnant women, and 30 pregnant women meeting clinical criteria for HG.31 While there was no statistical difference between IL-2 and IL-6 levels among women with HG and the other two groups, TNF-α was found to be significantly elevated in HG patients compared with both the healthy pregnant and the healthy nonpregnant groups. Kaplan's data suggest that TNF-α may play a role in HG, although it is not clear whether cytokines are causative agents of liver disease associated with HG and liver disease or simply just by-products of the disease. Recent mouse models, however, have shown that elevated levels of TNF-α may directly lead to T-cell apoptosis within the liver which in turn could cause liver damage.32 Moreover, liver biopsies of mouse models genetically engineered to express high levels of TNF-α showed typical features of active hepatitis including lymphocytic infiltration and necrosis.33 While these findings are intriguing and may provide future avenues of investigation, the precise role of cytokines in HG and other pregnancy-induced liver disorders is as yet undetermined.

The Impaired Mitochondrial Fatty Acid Oxidation Defect Hypothesis

As highlighted in Chapter 5, fatty acid oxidation (FAO) is the principal means by which humans generate energy for survival. FAO usually occurs in the mitochondria of cells but can also take place in peroxisomes. Mitochondrial FAO involves transport of free fatty acids (FFA) across selectively permeable mitochondrial membranes and requires multiple successive steps catalyzed by distinct enzymes.34 The end products of FAO are the reduced forms of flavin adenine dinucleotide (FADH2) and nicotinamide adenine dinucleotide (NADH). The subsequent electron transfer from FADH2 and NADH ultimately to adenosine diphosphate (ADP) in oxidative phosphorylation leads to the production of energy-rich adenosine triphosphate (ATP).34

Pediatric defects in FAO are recessively inherited and have recently emerged as an important group of inborn errors of metabolism with clinical significance.35 Affected patients with FAO defects usually present in the first year of life with a Reye's-like syndrome complicated by hypoglycemia and encephalopathy. Coma and death quickly ensue unless the disorder is rapidly recognized and treated. Conversely, patients heterozygous for mutations in the FAO cascade are usually phenotypically normal except during periods of oxidative stress such as starvation and pregnancy.

As discussed extensively in Chapters 4 and 5, fetal FAO defects are now recognized to cause AFLP and the HELLP syndrome in the obligate heterozygous mothers during the third trimester.36 The most commonly reported enzymatic mutation in the FAO pathway leading to pregnancy-induced liver disease is that of long chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD).34 A retrospective review of the obstetric records of 29 Finnish infants diagnosed with LCHAD deficiency by Tyni et al showed that over 10% of those pregnancies were complicated by HG in the other.37 Fetal mutations in other enzymes of the FAO pathway leading to HG have also surfaced.34,38 Innes et al reported a case of HG linked with fetal deficiency of hepatic carnitine palmitoyltransferase I (HCPT I), the enzyme responsible for actively transporting long chain FFA from the cytoplasm of cells across the outer mitochondrial membrane.39

Recent research underscores the importance of mitochondrial FAO in placental metabolism and subsequent fetal development. While maternal glycolysis was for years felt to represent the principal fetal metabolic source, Strauss and colleagues showed that the activity of the enzymes of FAO is high in placental tissues, especially during the first-trimester.40 Furthermore, FAO-deficient mouse models have been shown to suffer from intrauterine fetal growth retardation, hypoglycemia and early death.41

In light of all available data, we speculate that women heterozygous for FAO defects develop HG associated with liver disease while carrying fetuses with FAO defects due to the accumulation of fatty acids in placenta and subsequent generation of reactive oxygen species. Alternatively, it is possible that starvation leading to peripheral lipolysis and increased load of fatty acids in maternal-fetal circulation, combined with reduced capacity of the mitochondria to oxidize fatty acids in mothers heterozygous for FAO defects, can also caused HG and liver injury while carrying nonaffected fetuses. This hypothesis is illustrated in Figure 2.

Figure 2. A unifying hypothesis for development of liver disease in HG secondary to fetal and/or maternal defect in fatty acid oxidation.

Figure 2

A unifying hypothesis for development of liver disease in HG secondary to fetal and/or maternal defect in fatty acid oxidation. Fetuses with defective FAO may lead to accumulation of fatty acid and their metabolites in the placenta with subsequent placental (more...)

Liver Disease Associated with Hyperemesis Gravidarum and Fetal Fatty Acid Oxidation Defects

Since mitochondrial FAO is highly active in predominantly fetal-derived placental tissues,40 FFA intermediates might accumulate in the placenta of pregnancies complicated by fetal FAO defects. Studies in nonobstetric populations have shown that FFA intermediates can lead to free-radical induced damage to cellular membranes with activation of the cytochrome P-450 and lipid peroxidation.42,43 Fetal-derived FFA intermediates could then lead directly to placental endothelial damage followed by the recruitment of inflammatory cytokines ultimately circulated to the maternal liver. Damage to the maternal liver could follow, since inflammatory cytokines are potentially hepatotoxic.32,33

Liver Disease Associated with Hyperemesis Gravidarum and Nonaffected Fetuses

The starvation commonly seen in patients with HG can lead to enhanced peripheral lipolysis and an increased influx of FFA into mitochondria. Heterozygous mothers, while usually phenotypically normal, have limited capacity for mitochondrial FAO which subsequently leads to increased levels of plasma FFA intermediates and causes enhanced extramitochondrial FAO leading to the generation of reactive oxygen species. The maternal-derived FFA intermediates which accumulate in the circulation of the obligate heterozygous mothers could induce free-radical damage of placental endothelium with the subsequent release of inflammatory cytokines, resulting in maternal liver damage.

Summary

NVP is a common affliction during the first trimester of pregnancy, of which HG represents the most severe form. Liver involvement occurs in nearly one-half of all cases of HG and typically consists of mild elevation in serum transaminases. Liver test abnormalities resolve quickly in most cases after cessation of vomiting and volume repletion. No long-term sequelae of liver dysfunction have been described in mothers suffering with HG and liver test abnormalities. The pathogenesis of liver disease in HG is likely multifactorial. Starvation injury, placental inflammatory cytokines, and impaired FAO in either the fetus and/or mother are all likely to play a part. More research is required to help clarify the roles of the above factors, as well as the roles of as yet undetermined factors, in the etiology of the pregnancy-induced liver disease in HG.

References

1.
Weigel MM, Weigel RM. Nausea and vomiting of early pregnancy and pregnancy outcome. An epidemiological study. Br J Obstet Gynaecol. 1989;96:1304–1311. [PubMed: 2611169]
2.
Broussard C, Richter J. Nausea and vomiting of pregnancy. Gastroenterol Clin North Am. 1998;27:123–151. [PubMed: 9546087]
3.
Klebanoff MA, Koslowe PA, Kaslow R. et al. Epidemiology of vomiting in early pregnancy. Obstet Gynecol. 1985;66:612–616. [PubMed: 3903578]
4.
Fairweather DV. Nausea and vomiting in pregnancy. Am J Obstet Gynecol. 1968;102:135–175. [PubMed: 4877794]
5.
Quinlan JD, Hill DA. Nausea and vomiting of pregnancy. Am Fam Physician. 2003;68:121–128. [PubMed: 12887118]
6.
Koch KL, Stern RM, Vasey M. et al. Gastric dysrhythmias and nausea of pregnancy. Dig Dis Sci. 1990;35:961–968. [PubMed: 2384042]
7.
Jednak MA, Shadigian EM, Kim MS. et al. Protein meals reduced nausea and gastric slow wave dysrhythmic activity in first trimester pregnancy. Am J Physiol. 1999;277:G855–861. [PubMed: 10516152]
8.
Goodwin TM. Hyperemesis gravidarum. Clin Obstet. 1998;41:597. [PubMed: 9742356]
9.
Wu CY, Tseng JJ, Chou MM. et al. Correlation between Helicobacter pylori infection and gastrointestinal symptoms in pregnancy. Advan Ther. 2000;17:152–158. [PubMed: 11183452]
10.
Philip B. Hyperemesis gravidarum: Literature review. WMJ. 2003;102:46–51. [PubMed: 12822290]
11.
Koch KL, Frissora CL. Nausea and vomiting during pregnancy. Gastroenterol Clin Am. 2003;32:201–234. [PubMed: 12635417]
12.
Tsang I, Katz V, Wells S. Maternal and fetal outcomes in hyperemesis gravidarum. Int J Gynecol Obstet. 1996;55:231–235. [PubMed: 9003948]
13.
Abell T, Riely C. Hyperemesis gravidarum. Gastroenterol Clin North Am. 1992;21:835. [PubMed: 1478739]
14.
Wong HY, Tan JYL, Lim CC. Abnormal liver function tests in the symptomatic pregnant patient: The local experience in Singapore. Ann Acad Med. 2004;33:204–208. [PubMed: 15098635]
15.
Larry D, Rueff B, Feldmann G. et al. Recurrent jaundice caused by recurrent hyperemesis gravidarum. Gut. 1984;25:1414. [PMC free article: PMC1420189] [PubMed: 6510771]
16.
Conchillo JM, Koek GH. Hyperemesis gravidarum and severe liver enzyme elevation. J Hepatol. 2002;37:162–166. [PubMed: 12076879]
17.
Orazi G, Dufour PH, Puech F. Jaundice induced by hyperemesis gravidarum. Int J Gynecol Obstet. 1998;61:181–183. [PubMed: 9639224]
18.
Bacq Y, Funai EF, Riely CA. Hyperemesis gravidarum Up To Datewww.utdol.com.
19.
Knox TA, Olans LB. Liver disease in pregnancy. N Engl J Med. 1996;335:569–576. [PubMed: 8678935]
20.
Adams RH, Gordon J, Combes B. Hyperemesis gravidarum. I Evidence of hepatic dysfunction. Obstet Gynecol. 1968;31:659. [PubMed: 5646397]
21.
Webber B, Freiman I. The liver in kwashiorkor. Arch Pathol. 1974;98:400–408. [PubMed: 4138580]
22.
Mahn J, Duraldestin P, Dhumeaux D. et al. Biliary transport of cholephilic dyes: Evidence for two different pathways. Am J Physiol. 1977;232:E445–450. [PubMed: 871154]
23.
Friis R, Vaziri D, Akbarpour F. et al. Effect of rapid weight loss supplemented fasting on liver tests. J Clin Gastroenterol. 1987;9:204–207. [PubMed: 3571895]
24.
Morali GA, Braverman DZ. Abnormal liver enzymes and ketonuria in hyperemesis gravidarum. J Clin Gastroenterol. 1990;12:303–305. [PubMed: 2362099]
25.
Romero R, Mazor M. Infection and preterm labor. Clin Obstet Gynecol. 1988;31:553–584. [PubMed: 3066544]
26.
Kameda T, Matsuzaki N, Sawai K. et al. Production of interleukin-6 by normal human trophoblast. Placenta. 1990;11:205–213. [PubMed: 2371251]
27.
Li Y, Matsuzaki N, Masuhiro K. et al. Trophoblast-derived tumor necrosis factor-alpha induces release of human chorionic gonadotropin using interleukin-6 and IL-6-receptor-dependent system in the healthy human trophoblasts. J Clin Endocrinol Metab. 1992;74:184–191. [PubMed: 1727819]
28.
Casey ML, Cox SM, Beutler B. et al. Cachectin/tumor necrosis factor-alpha formation in human deciduas: Potential role of cytokines in infection-induced preterm labor. J Clin Invest. 1989;83:430–436. [PMC free article: PMC303698] [PubMed: 2913048]
29.
Romero R, Manogue KR, Mitchell MD. et al. Cachectin-tumor necrosis factor in the amniotic fluid of women with intraamniotic infection and preterm labor. Am J Obstet Gynecol. 1989;161:336–341. [PubMed: 2764054]
30.
Neuman MG. Cytokines—central factors in alcoholic liver disease. Alcohol Res Health. 2003;27:307–316. [PubMed: 15540802]
31.
Kaplan PB, Gucer F, Sayin NC. et al. Maternal serum cytokine levels in women with hyperemesis gravidarum in the first trimester of pregnancy. Fertil Steril. 2003;79:498–502. [PubMed: 12620429]
32.
Murray DA, Crispe IN. TNF-alpha controls intrahepatic T-cell apoptosis and peripheral T-cell numbers. J Immunol. 2004;173:2402–2409. [PubMed: 15294953]
33.
Mohammed FF, Smookler DS, Taylor SE. et al. Abnormal TNF activity in Timp3-/- mice leads to chronic hepatic inflammation and failure of liver regeneration. Nat Genet. 2004;36:969–977. [PubMed: 15322543]
34.
Rakheja D, Bennett MJ, Rogers BB. Long-Chain L-3-Hydroxyacyl-Coenzyme a dehydrogenase deficiency: A molecular and biochemical review. Lab Invest. 2002;82:815–824. [PubMed: 12118083]
35.
Ibdah JA, Yang Z, Bennett MJ. Liver disease in pregnancy and fetal fatty acid oxidation defects. Mol Genet Metab. 2000;71:182–9. [PubMed: 11001809]
36.
Schoeman MN, Batey RG, Wilcken B. Recurrent acute fatty liver of pregnancy associated with a fatty-acid oxidation defect in the offspring. Gastroenterology. 1991;100:544–548. [PubMed: 1985050]
37.
Tyni T, Ekholm E, Pihko H. Pregnancy complications are frequent in long-chain 3-hydroxyacyl-coenzyme a dehydrogenase deficiency. Am J Obstet Gynecol. 1998;178:603–608. [PubMed: 9539533]
38.
Ibdah JA, Bennett MJ, Rinaldo P. et al. A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women. N Engl J Med. 1999;340:1723–1731. [PubMed: 10352164]
39.
Innes AM, Seargeant LE, Balachandra K. et al. Hepatic carnitine palmitoyltransferase I deficiency presenting as a maternal illness in pregnancy. Pediatr Res. 2000;47:43–45. [PubMed: 10625081]
40.
Shekhawat P, Bennett MJ, Sadovsky Y. et al. Human placenta metabolizes fatty acids: Implications for fetal fatty acid oxidation disorders and maternal liver diseases. Am J Physiol Endocrinol Metab. 2003;284:E1098–E1105. [PubMed: 12582009]
41.
Ibdah JA, Paul H, Zhao Y. et al. Lack of mitochondrial trifunctional protein in mice causes neonatal hypoglycemia and sudden death. J Clin Invest. 2001;107:1403–1409. [PMC free article: PMC209324] [PubMed: 11390422]
42.
Mak IT, Kramer JH, Weglicki WB. Potentiation of free radical-induced lipid peroxidative injury to sarcolemmal membranes by lipid amphiphiles. J Biol Chem. 1986;261:1153–1157. [PubMed: 3003057]
43.
Singh AK, Yoshida Y, Garvin AJ. et al. Effect of fatty acids and their derivatives on mitochondrial structures. J Exp Pathol. 1989;4:9–15. [PubMed: 2778551]
Copyright © 2000-2013, Landes Bioscience.
Bookshelf ID: NBK6104
PubReader format: click here to try

Views

  • PubReader
  • Print View
  • Cite this Page

Related information

  • PMC
    PubMed Central citations
  • PubMed
    Links to pubmed

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...