Lipids Flashcards
Which particular fatty acids are critically important to proper development as well as inflammatory and other physiological processes?
Arachidonic acid, eicosapentaenoic acid (EPA), and docohexaenoic acid (DHA)
What are the basic contents of triglyceride structure?
A glycerol backbone and various fatty acids attached in ester linkage at the carbon-1 (sn-1), carbon-2 (sn-2), and carbon-3 (sn-3) positions
Why does a gram of fat stored in tissue have more recoverable energy than a gram of carbohydrate?
TGs have a lower intrinsic level of oxidation than carb, and the weight contribution of water common to carbs and proteins is missing from lipids
Which fatty acids necessary for life can humans not synthesize and why?
Linoleic acid and alpha-linolenic acid. The specific desaturase enzymes that can introduce a doube bond past position 9-10 within a given fatty acid are absent, which prevents the de novo synthesis of linoleic and alpha-linoleic acids.
Linoleic acid and alpha-linolenic acid serve as precursors for the synthesis of which other necessary long-chain unsaturated fatty acids?
Arachidonic acid (AA) and docohexaenoic acid (DHA)
What is the intestinal activity that is critical for metabolism of long-chain TGs?
The emulsification process and micelle formation that makes TGs and fatty acid esters available for hydrolysis by intestinal lipases and esterases
What types of fats can be directly absorbed in the villi of the intestinal mucosa?
Ingested glycerol and individual fatty acids. MCT (medium-chain triglycerides) lipid emulsions can be directly absorbed without requiring either bile salts for emulsification or energy for uptake
What are ILEs (lipid injectable emulsion), and what concentrations are available in commercial ILEs?
Oil-in-water emulsions consisting of 1 or more TG-containing oils, glycerin, and a phospholipid emulsifier, available in concentration of 10%, 20%, and 30% (w/v).
How can hypertriglyceridemia occur with the provision of lipids in PN?
It occurs when the body cannot clear TGs from plasma lipids via oxidation and/or storage in adipose tissue, and it may be caused when the supply of lipids into the bloodstream exceeds lipoprotein lipase activity or when lipoprotein activity is reduced
What is the most common pathway of oxidative degradation of fatty acids?
Beta-oxidation
What is the suggested % of total energy as linoleic acid and alpha-linolenic acid that should be provided to prevent essential fatty acid deficiency (EFAD)?
1-4% for linoleic acid
0.25-0.5% for alpha-linolenic acid
The two 100% soybean oil-based emulsions available for IV use in the US provide what percent of total energy from linoleic and alpha-linolenic acid?
55-60% of energy from linoleic acid and 3-4% total energy from alpha-linolenic acid
What is the most common lipid regimen in adult PN patients with 100% soybean oil-based ILEs that is prescribed to meet EFA requirements?
500 ml of a 20% ILE may be given weekly
ASPEN guideline when using soybean oil emulsion as the sole IV fat sourse?
The ILE should be held for the first week or given at a maximum of 100 g/week if there is concern or risk for EFAD
In adult patients requiring PN, ILEs should not exceed ___ g lipid per kg per day
2.5 g
It is recommended that the infusion rate for ILEs does not exceed ___ gm/kg/hour, for what reason?
Recommended to limit the infusion rate so it does not exceed 0.11 gm/kg/hour to prevent potential adverse reactions or toxicities associated with rapid infusion
What strategies can prevent adverse metabolic outcomes when propofol is used concomitantly with nutrition support?
Clinicians should monitor serum TG concentration frequently (twice per week).
To lower the total fat dose and possibly improve TF clearance, lipids should be removed from PN solutions.
Recommendations for acceptable TG levels are <250 mg/dL 4 hours after ILE infusion for “piggy backed” lipids and <400 mg/dL for continuous ILE infusion.
Patient could be started on a hypocaloric, fat-free PN (=/< 20 kcal/kg/day) (if failed trophic EN).
What are the biochemical and clinical manifestations of EFAD (that were observed in patients requiring PN for extended periods of time [2-4 weeks])?
Clinical symptoms: increased susceptibility to infection, impaired wound healing, and immune dysfunction
Biochemical changes in response to linoleic acid deficiency are manifested by a decrease in linoleic acid and AA levels and an increase in the mead acid level (mead acid primarily produced in humans in the absence of EFAs)
Triene:tetraene ratio > 0.2
Why might EFAD occur rapidly in patients receiving fat-free PN administration?
Due to elevated insulin levels that prevent adipose tissue lipolysis.
Why might the period of time be extended before a patient exhibits EFAD when receiving hypocaloric fat-free PN or a cyclic feeding schedule of fat-free PN?
It is thought that when PN is cycled or hypocaloric PN Is provided, essential fatty acids are mobilized and enter the circulation as a result of increased lipolysis of endogenous fat stores in response to a reduction in serum insulin concentration. In addition, hypocaloric feeding prevents the risk of hepatic dysfunction that may occur if the energy deficit (caused by the removal of lipids) is corrected by increasing the energy from dextrose or protein to maintain energy requirements
How can essential fatty acid deficiency (EFAD) be prevented when a lipid-free PN regimen is initiated in the ICU?
Patients should be monitored for EFAD if all sources of lipids are removed from the diet for more than 2-4 weeks. The dosing of ILEs depends on energy expenditure, the patient’s clinical status, body weight, tolerance, and ability to metabolize lipids. Providing 2-4% of energy requirement as linoleic acid may correct EFA insufficiency. Should calculate the linoleic acid dose from 100% soybean ILE or an alternative ILE to ensure adequate dosing of EFAs. Initiation of low dose or trophic EN may also be used to offset risk of EFAD. A polymeric enteral formula containing soybean oil and a mixture of other high-linoleic oils may be used. Generally, a polymeric enteral formula that provides 10-15% of patient’s total energy requirements will supply adequate EFAs. However, when the patient is at high risk for fat malabsorption, or when enteral feeding is interrupted or stopped for a significant period (14 days) with no other lipid source provided, the linoleic acid dose and EFAD risk should be evaluated
What is the ASPEN recommendation regarding the use of immune modulating formulations in critical illness?
Immune-modulating enteral formulations of arginine with other agents - including EPA, DHA, glutamine, and nucleic acid - should not be used routinely in medical ICU. These formulas and similar ones (eg, fish oil with or without arginine) should not be administered to severely septic patients
Under which conditions does ASPEN recommend formulations that contain fish oil and arginine be considered?
Severe trauma and TBI
What is the primary source of SCFAs?
The large intestine via bacterial anaerobic fermentation of nondigestible dietary carbohydrates and fiber polysaccharides.
Fermentation of nondigestible carbohydrates and fiber polysaccharides produces which SCFAs?
Acetate, propionate, butyrate
Name some of the functions of SCFAs
A primary energy source for colonocytes, stimulation of water and sodium absorption in the colon, and trophic effects to the intestinal mucosa.
Which SCFA has been shown to be the most important in regulation and maintenance of colonic tissue and why?
Butyrate. An important role may be to modify inflammatory activity by inhibiting the release of the transcription factor, nuclear factor lambda-light-chain-enhancer, of activated B cells. Exhibits antitumorigenic effects on cancer cell lines and has been identified with gene regulation involving processes of cellular apoptosis, proliferation, and differentiation
Describe some differences between long-chain triglycerides and medium-chain triglycerides
MCTs are smaller and more water soluble, liberation of fatty acids through hydrolysis of MCTs in the intestinal lumen is significantly faster relative to LCTs, absorption of MCFAs is more rapid. MCTs do not require the presence of bile or pancreatic lipases for absorption and are transported directly to the liver via the portal vein. MCTs not stored to any significant degree in adipose tissue, nor do they affect reticuloendothelial system. MCTs are ketogenic, and may provide a useful energy source for enterocytes, lymphocytes, and cells of other tissues in hypermetabolically stressed patients. Oxygenation of MCTs is less affected by glucose and insulin than LCTs. Oxidation of LCTs can be impaired by slow elimination rates from the plasma or by the requirement of carnitine for intracellular transport; metabolism of MCTs is a carnitine-independent system for transport into the mitochondria.
What is the energy density of MCTs?
8.3 kcal/g
What are structured lipids?
“Designer” TG molecules that are specifically synthesized in the lab via chemical and/or enzymatic methodology or via genetic engineering. These TG mixtures contain a randomly esterified pattern of MCTs and LCTs that can contain within the same TG molecule both MCFAs and LCFAs
What are some benefits of a structured lipid?
Offer a defined mechanism to rapidly deliver MCFAs and to provide a more rapid availability of EPA and DHA with the entire attendant array of nutritionally positive aspects of these substances. Benefits also include better fatty acid absorption, lower infection rates, improved hepatic, renal, and immune function.
How do fatty acids in the omega-6 family influence the immune system?
Alteration of membrane structure and function, by modulation of immune function through AA metabolites, and by stimulation of inflammatory cytokines
What is Smoflipid?
A newer generation alternative ILE that is composed of a blend of soybean oil, olive oil, fish oil, and MCTs. Available in US. Contains approximately 67% less linoleic acid than soybean oil.
What is ClinOleic/Clinolipid?
A blended, alternative ILE composed of soybean and olive oil. Not commercially available in US. Contains approximately 66.2% less linoleic acid than soybean oil.
Why have commercial ILEs with high olive oil content been developed?
To reduce omega-6 fatty acid and thus the risk associated with in vivo oxidative stress and the potential for a proinflammatory environment
Describe various differences in olive-oil ILE compared to soybean oil ILE
Olive oil-based ILEs are less inhibitory of various neutrophil responses, including human neutrophil viability, phagocytic activity, inflammatory cytokine production, and oxidative burst induction. Greater immune-neutral effect
What are the benefits of MCT-LCT emulsions (50:50 w/w mixture) in PN solutions?
Providing a better oxidized energy source, improving nitrogen balance (attenuating protein catabolism in stress), and providing rapid clearance of lipid from the blood. Patients getting these emulsions have been shown to have a fatty acid profile that is closer to normal when compared with individuals who receive soybean-based ILEs
Which of the following showed improved nitrogen balance, more protection of the liver, more efficiently eliminated TGs, and a strong trend toward a shorter hospital LOS? Structured lipid, MCT-LCT PN emulsion (structured lipid group), or a physically mixed MCT-LCT PN emulsion (MCT/LCT group)?
Structured lipid group
What are the most common phytosterols and what are they?
Campesterol, sitosterol, and stigmasterol. They are plant analogues of cholesterol and are found in all currently available plant-based ILE formulations. May interfere with bile acid homeostasis
What is the hypothesis that data is consistent with regarding phytosterols in plant-based ILE formulations?
High phytosterol exposure is associated with PNALD and, reduction of soybean-based ILE and/or use of fish oil that does not contain any phytosterols can reduced the incidence of PNALD
