Newsletter July 1997
SHORTAGE OF PARENTERAL MULTIVITAMINS
While this shortage was initially believed only to affect MVI Paediatric © there is now further information to suggest that current production of MVI-12 is unable to meet the demand of the international market. As a result it is likely we are also to experience shortages of MVI-12 in Australia within months. While these shortages were initially believed to be short-term it is now feared that the problem will be more long-term. Alternative sources of vitamins suitable for intravenous use are being sought internationally and information will be provided as soon as this becomes available. In the meantime the following recommendations are advised.
RECOMENDATIONS FOR PAEDIATRICS
The only IV multivitamin preparation suitable for paediatric patients in Australia currently is MVI-Paediatric. In view of the current shortages alternative multivitamin preparations have been investigated and recommendations for these products will be available soon. Until an alternative paediatric multivitamin preparation is available in Australia the following suggestions have been made:-
Neonates less than 36 weeks gestation or under 1500g
Reserve MVI-Paediatric for use in neonates <36 weeks gestation or under 1500g. Infants and children are at greatest risk of developing vitamin deficiency. MVI-12 contains propylene glycol and polysorbate 80 and 20 which may be potentially toxic for neonates. Therefore MVI-12 should not be substituted for MVI-Paediatric in infants <1500 grams.
Infants >1500g and >36 weeks gestation and children <11 years of age
To compensate for these deficiencies it is suggested that Vitamin K, 200 mcg/day should be added in infants >2.5 kg and children. In preterm infants <2.5 kg, Vitamin K added at a dose of 80 mcg/kg/d is suggested. If calcium and phosphate is adequate in the parenteral nutrition solution it is believed that the dose of vitamin D provided in MVI-12 at 2 ml/kg will be sufficient for most patients. Infants and children with rickets or metabolic bone disease may require additional Vitamin D. Vitamin E is not currently available commercially as an individual IV product. The dose of Vitamin A required is not well defined in low birth weight infants. Vitamin A requirements above that present in MVI-Paediatric should be assessed on an individual patient basis.
RECOMMENDATIONS FOR CHILDREN >11 YEARS OF AGE AND ADULTS
Patients receiving long-term TPN are at greatest risk of developing clinically significant deficiencies in the absence of parenteral multivitamins. In the US cases of vitamin deficiency due to this shortage have already been reported. Vitamins at particular risk of causing clinical problems due to deficiency in these patients include:
At this stage it is suggested that stocks of MVI-12 be conserved as long as possible by:
Dr Julie Bines, President of AuSPEN.
In this era of political and economic change the Council believes that it is timely to reassess the aims and responsibilities of the Society. To help with this process it has been proposed that a Planning Meeting be conducted on 20th and 21st September. We would like to encourage anyone with ideas, suggestions or issues for discussion to contact Dr Julie Bines or Dr Margaret Allman. Some topics worth considering are Membership, Affiliations with other Professional Societies, Educational Roles, Advisory Roles at the State and Federal Govt. levels, Communication with Members, Role in Research and Development, Role in Professional Development, Interaction with Commercial Organisations, International Links, etc.
As this Newsletter is going to press the Conference flyer and Registration documents are going through their final draft prior to printing. As a result the most up to date information will be given on a `Stop Press' flyer in this Newsletter. In addition we will use the AuSPEN Homepage to post new developments and information as and when they come to hand.
Main Programme Topics
Guest Speakers :
We are privileged to have excellent international guest speakers:
Workshops are planned for Thursday afternoon which, due to the time difference, will still allow many delegates to fly in on Thursday morning and be able to attend the afternoon sessions. Our international speakers have agreed to participate in the workshop(s).
The Esplanade Hotel in Fremantle is an outstanding conference venue with recent refurbishments enhancing all aspects of the hotel, including the convention facilities and accommodation. Social functions are being planned to make the most of these opportunities and we can guarantee you will enjoy them. We will be especially encouraging everyone to attend the Thursday night cocktail party and the Friday night dinner which we intend to make memorable occasions. We hope to see you all here?
The Conference Organising Committee for Perth 1997:
Please contact any of the above if you have particular queries about the Conference.
Registration Brochures for the 23rd Scientific Meeting are on their way
Guest Speakers confirmed
No increase in Registration Fees
Dr. Paul Woods, Intensive Care Unit, Sir Charles Gairdner Hospital, Nedlands, Western Australia, 6009
The body of the abstract should contain:
An introduction including the study hypothesis:
Abstracts should be prepared in the following manner:
Your abstract can be considered for an oral presentation or a poster presentation. Please indicate your preference. Written confirmation of your presentation style will be forwarded by September 26, 1997.
CLOSING DATE FOR ABSTRACTS
COMPLETE THE FORM ENCLOSED AND RETURN IT WITH YOUR SUBMISSION TO:
Please circle your Presentation preference................ORAL............POSTER
IMPORTANT: The Registration Form can only be accepted if accompanied by full payment and accommodation deposit if applicable.
Attention: Non Members If you wish to join the Society and take full advantage of being a member, please contact Dr. Margaret Allman (02) 9351 3758 for an application form.
ACCOMMODATION REQUEST - ANNUAL SCIENTIFIC MEETING
[.....] [.....] [.....] [.....] [.....] [.....] [.....] [.....] [.....] [.....] [.....] [.....] [.....] [.....] [.....] [.....]
Signature: .................................................................. Exp.Date: ..............................
Cheques should be made payable to AuSPEN and forwarded to the Conference
Secretariat: Susan Adler Conference Planning 72 Napier St, COTTESLOE WA 6011. Telephone/Facsimile: (08) 9384 4213
ACKNOWLEDGEMENT OF REGISTRATIONS
All registrations received at the Secretariat by October 10 will be acknowledged in writing.
REFUND & CANCELLATION POLICY
A refund of Registration Fees, less a service fee of $95, will be made if notification is received in writing at the Secretariat prior to September 19, 1997. Requests for refunds received after this date will be considered individually. All refunds will be made after the conclusion of the Conference.
Accommodation is available at the following hotels. Block Bookings will be held until the end of August with the exception of the Esplanade Hotel who will hold rooms up till one month prior to the conference. Please let Conference Secretariat know as soon as possible if you have accommodation requirements. A deposit of one nights accommodation is required with your booking. All prices quoted below are on a per night basis.
The final Newsletter for this year will be published in October this year; the first one in 1998 will be appear in January. If contributors could get items to the Editor by the middle of the third week of the month preceeding that will assist greatly with the planning of the issue. If copy is not ready at that time but will be by the end of that month please let me know so that I can reserve the space.
Contributions on any relevant subject are always very welcome. If you have an idea for an article but are not too sure about its relevance do not hesitate to give the Editor a call or email to discuss and develop the idea first.
The Editor has been forwarded brochures etc. on the following two meetings. Photocopies can be supplied on request.
October 29th - 31st, The 3rd Congress of PENSA (The Parenteral and Enteral Nutrition Society of Asia) will be held in Bangkok at the Central Plaza Hotel. The programme includes
Registrations are due by the 1st October 1997.
Contact : Assist Prof Preyanuj Yamwong MD, Research Centre for Nutritional Support, Faculty of Medicine, Siriraj Hospital, Bangkok 10700, Thailand. Ph 66-2-419-7740-1 Fax 66-2-412-9841
email : email@example.com
January 19th - 21st, 1998. 22nd Clinical Congress of ASPEN, will be held in Orlando, Florida, USA. The organisers have provided copies of the forms required to submit a Scientific Paper or a Nutrition Practice Poster. The dateline for the receipt of either abstract is 22nd August 1997. "The Nutrition Practice Poster Session" provides an informal forum for the exchange of information of the practice of nutrition support and metabolic care of patients. It is especially suited for nutrition support practitioners to present information on their unique experiences in team management, patient care, and case studies as well as small clinical studies reporting on clinical outcomes, drug utilisation and evaluation, clinical observations, and use of computer or information technology in nutrition support practice. The Nutrition Practice Poster Session is not the appropriate forum for the presentation of significant basic or clinical research. Abtracts that report the results of hypothesis based research studies (basic or clinical) will not be accepted by the Nutrition Practice Poster Review Committee, but should be submitted to the Scientific Abstract Review Committee using the "Scientific Abstract Form."
July 23 - 26, 1997. Sixth World Congress on Clinical Nutrition : Antioxidants and Disease, Banff, Alberta, Canada. Contact Tapan Basu, Dept of Agricultural Food and Nutritional Sciences, University of Alberta, Edmonton, AB T6G 2P5, Cananda. (403)4 92- 4921 . Fax 403-492-9130.
July 20th - 23rd. 2nd World Congress of Allied Health Professionals :'Sustainable Health Care in the 21st Century. A Global Perspective'. University of Wolverhampton, Priorslee Hall, Telford, Shropshire, England. email firstname.lastname@example.org
July 27 - Aug 1 : 16th International Congress of Nutrition . Montreal. Contact Congress Secretariat, IUNS '97, National Research Council Canada, Building M-19, Montreal Road, Ottawa, ON, Canada K1A OR6. (613)993-7271. Fax 613-993-7250.
August 31st - September 3rd. : 19th ESPEN Congress on Clinical Nutrition and Metabolism. Rai Congress Centre, Amsterdam. Contact : Van Namen and Westrerlaken Congress Organisation Services, PO Box 1558, 6501 BN Nijmege, The Netherlands. Ph 31-24-3234471 Fax 31-3360-1159.
September 7th - 11th : Tachykinins in Health and Disease. Cairns, Queensland. Home Page = http://iuphar.pharmacology.unimelb.edu.au/iupar/meeting_970907.html
September 12th - 13th : 'New Concepts in Lipid Nutrition' is the theme of the Annual Meeting of the European Academy of Nutritional Sciences, Warsaw, Poland. Contact : Anna Gronowska-Senger or Mariola Arauez, Department of Human Nutrition, Warsaw Agricultural University (SGGW), Nowoursynowska 166, 02-787 WARSAW, Poland.
October 1st - 5th. VIIIth Biennial Meeting of the International Society for Free Radical Research. Contact. Mr Merce Ferrer, Pacifico SA, E Granados, 44 Pral., 08008 Barcelona Spain. Tel +34-3-4545400. Fax +34-3-4517438
October 16th - 19th : 22nd Australia & New Zealand Intensive Care Society Scientific Meeting, Wrest Point Convention Centre, Hobart, Tasmania. Keynote Speakers : Prof. Michael Pinsley, Dr Stephen Crawford and Ms Karin Mitchell-Supple e. Contact Cartherin Gordon, 22nd Annual Scientific Meeting, PO Box 255, SANDY BAY 7006. Ph 03-6222-8013, Fax 03-6222-8010. Email email@example.com
October 24th - 25th. 23rd Annual Scientific Meeting of AuSPEN, at the Esplanade Hotel, Fremantle, Western Australia. Contact Dr Paul Woods, +61-9-346-3333 Ext 1010 or Fax +61-9-386-8541 or Susan Adler Conference Planning Ph/Fax +61-9-384-4213
November 1st - 3rd : Annual Paediatric Nutrition Workshop: 'Nutrition during Adolescence' at Royal's Children Hospital, Brisbane, Queensland. Sponsored by Children's Nutrition Research Centre, Department of Paediatrics and Child Health, University of Queensland. Contact Charles Fleetwood, Consult Fleetwood Management Services, P.O. Box 5560, Stafford Heights, Qld 4053. Phone: 07 3264 5970, Fax: 07 3264 3520. Email: firstname.lastname@example.org.
November 13th - 17th. 23rd Annual Scientific Meeting of the Society of Hospital Pharmacists of Australia, Adelaide Convention Centre, South Australia. Further details from Dave Cosh, Pharmacy Dept, Repatriation General Hospital, Daw Park, SA 5041. Ph 08-2751-799 Fax 08-3740-225 email email@example.com, or from Hartley Management Group Pty Ltd, PO Box 20, Kent Town, SA 5071, Ph 08-363-4399, Fax 08-3634-577, email firstname.lastname@example.org.
November 30th - December 2nd. 21st Annual Scientific Meeting of the Nutrition Society of Australia, Brisbane, Queensland. Further information contact Joan Breakey, 75, Bishops Road, BEACHMERE Ph: 07-496-8207 email : email@example.com
April 30th - May 2nd 1998 : 8th Beijing International Symposium of Parenteral and Enteral Nutrition. Beijing International Hotel, Beijing, China. Contact : Dr Zhu-Ming Jiang, Department of Surgery, Peking Union Medical College Hospital, Geiji ng 100730, China. Ph 6513-4563 Fax 8610-6512-4876 email firstname.lastname@example.org
September 16th - 19th 1998 : 20th ESPEN Congress on Clinical Nutrition and Metabolism will be held in Nice, France. Contact : Nice Acropolis, Development Dept., 1 Esplanade Kennedy, BP 83, 06302 Nice Cedex 4, France. Ph 33-04-9392-8300 Fax 33-04-9392-8255
October 31st - November 3rd 1998 : Growth Factors and Nutrients in Intestinal Health and Disease. International GUT Symposium, Osaka, Japan. Contact : Dr Kinya Sando, Dept of Paediatric Surgery, Osaka University Medical School, 2-2 Yamadaoka , Sui ta, Osaka, 656, Japan. Ph 81-06-8793-753 Fax 81-06-7893-759
Rational classifications of amino acids has been a long standing interest. As an analytical biochemist I became familiar with the classification based upon their order of elution from an anion exchange chromatograph : acidics then neutrals then basics. With the advent of practical high pressure liquid chromatograhic (HPLC) methods this order no longer holds sway. In HPLC methods there are a variety of column fillings and elution programmes which in turn dictate their own character istic orders of elution. The classic dietary restriction experiments of Rose in the 1920's gave us the classification based on eight essential, two semi-essential and eleven non-essential amino acids. But in contemporary nutrition this classification is probably not that useful. So in this article I want to explore some other biochemical and physiological classifications of amino acids.
The first is to decribe the classification that arises out of a consideration of the metabolic charts from a largely 'catabolic' point of view; most of our TPN patients are in a catabolic state and so it could be argued to be an appropriate starting point. Others, however, may regard this as not being an entirely satisfactory approach for the TPN practitioner. In TPN our aim is to supply amino acids for protein synthesis not as an alternative source of amphibolic substrates for the Citric Acid Cycle. Surely a significant flux of infused amino acids down these pathways is reducing the TPN amino acid solution to an expensive caloric source ? That view will be balanced by a broad classification based upon a review of the organ uptake and release of amino acids which adds the perspective of amino acid fluxes to the discussion.
Gluconeogenesis From Amino Acids
The gluconeogenic cycle starts with the feeding in of Citrate originating from the conversion of Acetyl-CoA. The pathway then follows the following conversions :
Citrate -> Alpha-Ketoglutarate -> Succinyl-Coa -> Fumarate - > Oxaloacetate -> Glucose
Reference to the metabolic chart shows that at each point there is the possibility of feeding in these substrates from carbon skeletons that have been derived from amino acid sources. The following classification is based broadly upon these opportunities.
The Acetyl-CoA - Acetoacetate Equilibrium Group (LEU, ILE, PHE, TYR, LYS)
This equilibrium is fed by the irreversible conversions of the brached chain amino acids Leucine and Isoleucine, the aromatic amino acids Phenylalanine and Tyrosine and by the essential amino acid Lysine. Phenylalanine, Tyrosine and Leucine can form the ketone body acetoacetate and for this reason they are also classified as Ketogenic Amino Acids.
The Alpha-Ketoglutarate - Glutamate - Glutamine Equilibrium Group (GLU, GLN, HIS, PRO, HYP, LYS)
The members of this group, in addition to Glutamate and Glutamine are Histidine, Proline, Hydoxyproline and Lysine. Looking at the metabolic chart we can also see a dependence upon the Urea Cycle because the conversion of Glutamine to Glutamate involves the release of ammonia which must be metabolised by the Urea Cycle. The bidirectional nature of the Proline - Glutamate reaction also means that theoretically Proline levels can buffer Glutamate levels and vice versa. Alpha-ketoglutarate, which is not an amino acid, can also influence the level of Glutamate because that reaction is also bidirectional. The conversions of Histidine and Lysine to Glutamate, however, are unidirectional ie. strictly catabolic. The catabolic conversion of Lysine also feeds substrate into Acetyl-CoA - Acetoacetate Equilibrium Group.
The Succinyl-CoA Group (VAL, ILE, THR, MET)
The members of this group are Valine, Isoleucine, Threonine and Methionine. The conversions are all unidirectional and hence should be classified as catabolic.
The Fumarate Group (PHE, TYR)
The amino acids Phenylalanine and Tyrosine are catabolised to fumarate.
Oxaloacetate Group (ASP)This has a sole member - Aspartate - but this is a dynamic equlibrium and so the concentration of one should theoretically be able to buffer the concentration of the other.
The Pyruvate Group (MET, SER, CYS, TRY, ALA, THR, GLY)
Pyruvate does not exist within the Citric Acid Cycle but the unidirectional conversion of pyruvate to oxaloacetate is an important unidirectional reaction which can lead to the catabolism of the amino acids in this group viz Methionine, Serine, Cysteine, Tryptophan, Alanine, Threonine and Glycine. Within this group there are two equilibria involving three of the amino acids. The first involves Glycine and Serine which are interconvertable. The second involves Alanine and the non-amino acid pyruvate which form an equilibrium pair and are in fact the key components in the Glucose - Alanine Cycle. Amino groups from catabolised amino acids in muscle tissue are reacted with pyruvate to produce Alanine molecules which are then exported to the liver where they are deaminated back to pyruvate. The pyruvate is converted to glucose via oxaloacetate.
The Urea Cycle Group (ORN, ARG)
This is a simple cycle in which Ammmonia is reacted with Ornithine to form Arginine which is converted back to Ornithine with the release of a molecule of Urea.
This does not appear on the metabolic chart. It is synthesised from Cysteine Sulphinate via a unidirectional pathway.
This completes the classification scheme based upon the reactions involving amino acids that appear on Metabolic Charts. In closing this section it is appropriate to re-emphasise (1) Several amino acids have more than one entry point into the Citric Acid Cycle. (2) The possibilities for reversible reactions have the potential to act as buffers against the unidirectional flux of amino acids down catabolic pathways.
Metabolic Fluxes of Amino Acids
A Metabolic Chart lists the reactions that are possible in mammalian systems but does not necessarily show that some pathways may occur preferentialy in certain tissues and less in others. During the 1970's routine analyses of blood plasma for amino acids became a practical proposition and consequently the first experiments in organ uptake and release of amino acids were undertaken. Felig reviewed many of these in the 1975 Annual Review of Biochemistry, (Vol. 44, 1975). The the amino acids which demonstrated the major fluxes in the post absorptive statewere were as follows. Muscle exports Leucine, Isoleucine, Glutamine and Alanine. The gut is a net importer of Glutamine and exports Alanine. The kidney takes up Glutamine, Glycine and Proline and exports Alanine and Serine. The liver is a major importer of Alanine and Serine. Peripheral tissues are importers of Serine, Glutamine and Cysteine. These fluxes give a third dimension to the metabolism of amino acids. It is difficult to prepare a chart that illustrates this particularly because this third dimension is heavily dependent upon the time since the last meal and the endocrine and cytokine status of the individual at that particular time. In addition there is the possibility for effects which border on pharmacological when various amino acids are administered singly or in particular formulation profiles. For example is the preservation of gut integrity by the administration of Glutamine Dipeptide simultaneously with a routine TPN formula a nutritional response or a pharamcological effect given that the plasma Glutamine concentration almost doubled in the treatment group; (Lancet, v341, 1363-5, (1993))? Oral administration of Alanine, Glycine and Methionine as supplements to a casein based diet have each been shown increase the concentrations of urea cycle enzymes in rats (Snodgrass et al. J.Nutrit. 586, (1981)). Such enzyme inductions effectively increase the 'cycles per unit time' of the Urea Cycle ie. increase the capacity of the Urea Cycle to metabolise ammonia delivered to it via Glutamine. Rats with implanted Ward Tumour and then fed an Arginine - No Ornthine TPN solution showed enhanced tumour growth in comparison to Ornithine - No Arginine TPN solution fed Ward Tumour bearing rats. Could this be a pharmacological effect on the Urea Cycle in the tumour tissue; (Nutrit Cancer, v27, 102-6, (1997)). Animal nutritionists are interested in rapid growth of lean body mass. Their observation in healthy growing pigs suggest that 'after Lysine, Tryptophan, Threonine, Methionine and Isoleucine are the most common limiting amino acids in grower-finisher diets'; (Comp Cont Educ Prac Vet, v18, 1368, (1996)). Can these observations be extrapolated to apply in the TPN patient ? Clearly amino acid fluxes in various physiological states is a complex area and the following article by Anthony Kee explores and discus ses some of these possibilities in greater detail.
One of the most characteristic features of injury, sepsis and stress is loss of body weight and protein. There is no dedicated storage form of nitrogen in the body as virtually all nitrogen in the body is protein amino acids. Free amino acids in the blood and tissues comprise only a very small percentage (about 1%) of the total amino acid content of the body. Thus, the large and prolonged protein catabolism that occurs in critically individuals can lead to loss of normal physiological function and increase morbidity and mortality (22). Furthermore, hyper-metabolic individuals lose significant amounts of skeletal muscle as this is the major site of nitrogen in the body. Loss of muscle tone in these patients can compromise survival particularly when wasted intercostal muscles reduce the patient's ability to cough, which leads to sputum retention and pneumonia (1,22). Thus, the effects of stress on amino acid metabolism, particularly in skeletal muscle, has been an area of intense investigation.
As has been outlined in the accompanying article amino acid metabolism is to some extent tissue specific and there is therefore an extensive transfer of amino acids, via the blood stream, from one tissue to another. To understand the alterations in nitrogen metabolism that occurs during stressful situations one must have at least some information about inter-tissue amino acid exchanges or fluxes. Most of the data on amino acid fluxes have been obtained using the arteriovenous (AV) difference technique. In this technique the concentration difference of a substrate across a tissue bed, such as the leg, is measured. To give a more accurate measurement of flux the blood flow across the tissue bed must also be known. For this technique to give valid estimates of flux across tissues a number of criteria have to met. One of the most important criteria is that the venous blood must be obtained from vessels draining only the tissue of interest. In this regard there are potential difficulties in using peripheral tissue balance, ie leg or arm fluxes, as an indicator of muscle balance as the major veins of peripheral tissues drain a variety of tissues such as muscle, bone, connective and adipose tissue. There is some disagreement of the contribution of non-muscle tissues to the net balance of amino acids across peripheral tissues; values of between 10 and 60% have been reported (5,8). Whatever the true contribution of non-muscle tissue to peripheral flux the flux across the leg should provide a better estimate of skeletal muscle flux as it has a greater proportion of muscle to non-muscle tissue than the arm. Further discussion on this and other technical aspects of the AV difference technique can be found in the excellent review by Wernerman and Vinnars (18).
Amino Acid Fluxes Across Tissues in the Postabsorptive Period and During Starvation
As trauma is usually followed by a period of at least partial starvation it is necessary to understand the effects of starvation on amino acid tissue exchange before one can establish the effects of stress itself on amino acid metabolism. All tissue and organs of the body are involved in exchange of amino acids. However, quantitatively the major exchange of amino acids occurs between tissues of large size, ie, skeletal muscle, and/or high metabolic activity, ie liver, or tissu es that have large blood flow, ie., many visceral organs. Thus, the small intestine, liver, lungs, kidneys, skeletal muscle and brain are quantitatively the most important organs involved in exchange of amino acids in the body. In this review discussion will be largely confined to the skeletal muscle, liver, small intestine and kidneys as these are tissues for which there is most information available.
The small intestine is the major site of absorption of amino acids and small peptides resulting from digestion of dietary protein. Approximately 30% of dietary protein is composed of glutamine, glutamate, asparate and alanine. Alanine and a mmonia are the major nitrogenous compounds released into the portal vein indicating that there is extensive metabolism of dietary amino acids by the small intestine (20). In the postabsorptive state there is a large uptake of glutamine and release of alanine, glycine and citrulline across the portal drained viscera (9). Much of the glutamine taken up by the intestine is utilised for energy as it is the predominate oxidative fuel of the intestinal mucosa (21).
The liver removes approximately 75% of the total amino acids derived from dietary protein. The large uptake of amino acids by the liver results in synthesis of proteins and degradation of excess amino acids. In addition to endogenous proteins the liver produces and releases a large amount of proteins (albumin and other immunoproteins) into the circulation (11). The net uptake of amino acids, particularly alanine, glycine and glutamine, by the liver continues in the postabsorptive state because of the increase in proteolysis of extrahepatic tissues.
The rise in amino acid concentrations in the blood following a meal leads to a net uptake of amino acids by the peripheral tissues (6). The branched-chain amino acids (BCAAs), leucine, isoleucine and valine, account for approximately half the total amino acids taken up by the peripheral tissues in first 2h after a meal (6). In spite of the rise in circulating concentrations of glutamine and alanine after a meal the peripheral tissues continue to release large amounts of alanine and glutamine (6). In the postabsorptive state and after an over-night fast, there is a net output of amino acids from peripheral tissues of all amino acids except glutamate and the BCAAs (9). This net outflow of amino acids is due to an increase in muscle proteolysis. The release of glutamine and alanine from peripheral tissues is disproportionate to their content in skeletal muscle proteins which has led to the suggestion that these amino acids are synthesised from amino acids, particularly the BCAAs, arising form proteolysis within the muscle cell (16). As such glutamine and alanine are thought to act as non-toxic carriers of amino-nitrogen from the periphery to the splanchnic tissues. In such a role the alanine released from the limbs is taken up by the liver where its amino-N group is converted to ammonia and its carbon skeleton is utilised for synthesis of glucose (12).
In the postabsorptive state the kidneys extracts glutamine, aspartate, proline and citrulline and releases net amounts of serine, glycine and arginine (9). Glutamine is the major source of urinary ammonia formed in the kidney in the maintenance of acid-base balance. The kidneys have large activity of arginine synthetase and it is believed that much of the citrulline taken up by the kidneys is converted to arginine which is released into the circulation. This is a key reaction in the overall metabolism of arginine which involves the liver, intestine and kidneys. The net production of citrulline and ammonia (derived principally from glutamine deamidation) by the intestine is important for maintenance of the urea cycle in the liver during fasting. However, the liver cannot use citrulline directly because there is no transporter for citrulline in the liver (13). Instead, citrulline is taken up by the kidney, converted to arginine, via. arginine synthetase and released into the circulation. The liver in turn takes up this arginine, and urea and ornithine are released.
The Effects of Trauma, Sepsis and Stress on Amino Acid Fluxes Across Tissues
In general, stress results in an increase in peripheral efflux of amino acids with the magnitude of the increase related to the severity of insult (17). The proportions of amino acids released are comparable to those seen in the postabsorptive state with alanine and glutamine accounting for 40-60% of the total amino acid output. Associated with the increase in efflux of amino acids from the periphery is a decrease in skeletal muscle intracellular amino acid concentrations. Although many amino acids are decreased in the muscle during stress by far the greatest decrease in intracellular amino acid concentrations is for glutamine (17). The decrease in glutamine concentration is relatively rapid, occurring in the first few days after injury or surgery (14). In contrast, the normalisation of intracellular glutamine concentrations after elective surgery takes many months (14). It is not known whether the fall in intramuscular glutamine concentration has any effect on muscle function. Although it has been observed that decrease in intramuscular glutamine is proportional to the severity of the stressful insult. A number of investigators believe that the fall in glutamine concentration is a major stimulus for the net loss of muscle protein that occurs in stressful situations (15). However, evidence for a direct causal link between glutamine concentration and protein turnover has yet to be obtained.
Markers of Muscle Protein Balance.
Tyrosine and phenylalanine are two amino acids which are not synthesised or degraded in peripheral tissue. Thus, a net input or output of tyrosine or phenylalanine from peripheral tissues indicates a state of net proteosynthesis or proteolysis, respectively. Thus, following trauma a net efflux of tyrosine and phenylalanine is commonly observed (8). 3-methylhistidine is another marker of muscle protein breakdown. This amino acid is found predominantly in the myofibrillar proteins actin and myosin and is produced by post-translational methylation of histidine residues in proteins. It can not be reutilised or degraded by any tissue in the body (23). Thus, an increase in 3-methylhistidine efflux from the peripheral tissues, as occurs following surgery, indicates an increase in net proteolysis.
There is a reciprocal relationship between peripheral and splanchnic amino acid fluxes. Following surgery there is a marked increase in uptake of amino acids by the splanchnic region (11). This is due to a large increase in glutamine uptake by the liver and intestinal tissues, and a large hepatic uptake of alanine arising from the intestines. The uptake of amino acids by the splanchnic tissues following trauma serves two purposes. Firstly, the carbon skeletons of the amino acids are used for glucose production, and secondly, the extra amino acids are utilised for increased production of acute phase proteins.
Mediators of the Increased Peripheral Tissue Amino Acid Release During Stress
The flow phase of injury is generally characterised by increased plasma concentrations of insulin, glucagon, cortisol, adrenaline and noradrenaline (3). However, the concentrations of these hormones are quite variable, particularly the catecholamines (3). In spite of the increased insulin concentrations following surgery and during critical illness hyperglycaemia develops, fat oxidation increases and there is a net loss of protein from the skeletal muscle (3). Thus, a state of insulin resistance develops following surgery and critical illness.
The importance of the counter-regulatory hormones, glucagon, cortisol and the catecholamines in mediating the metabolic response to the flow phase of injury has been demonstrated by a number of investigators who infused them into normal volunteers at a rate to give plasma concentrations similar to those seen in the flow phase of injury (2). These investigators were able to stimulate the hyperglycaemia, hyperinsulinemia, increased energy expenditure and muscle protein catabolism, and insulin resistance of injured patients (2). However, the magnitude of the protein catabolic response is far less following hormone infusions than it is in severely stressed patients. This is undoubtedly due to the added catabolic actions of cytokines which are elaborated during critical illness but would not be expected to be increased during hormone infusion in healthy subjects.
The increased concentration of growth hormone and the counter-regulatory hormones in the flow phase of injury and during sepsis lead to an increased mobilisation of endogenous fuels, glycogen and amino acids, for maintenance of endogenous glucose. The cells involved in inflammation and wound repair rely on glucose as a primary fuel (19). Thus, the increased glucose turnover may be seen as a way of optimising host defenses and ensuring wound repair by providing essential fuel for inflammatory and reparative tissue. However, continued utilisation of amino acids leads to muscle wasting and loss of essential functions which are associated with negative outcomes.
Effect of Intravenous Nutrition on Inter-Tissue Amino Acid Exchange
In general, the effects of IVN on inter-tissue amino acid exchange are qualitatively similar to that of oral nutrition. Glucose infusion decreases the net release of amino acids from the periphery by mainly reducing the release of alanine (7). The reduction in alanine release is no doubt a response to a decrease in gluconeogenesis that occurs with glucose infusion. Amino acid infusion stimulates uptake of most amino acids across the splanchnic region and peripheral tissues, the only exception being alanine and glutamine who's output from the muscle increases or remains unchanged (10). The peripheral uptake of amino acids is dependant on the level of amino acid intake (10). We have found that to produce a net peripheral uptake of amino acids in preoperative relatively unstressed patients 0.4 gN/kgBW/day of a balanced TPN regimen is required, while only 0.22 - 0.25 gN/kgBW/day of oral nutrients are required to stimulate peripheral amino acid uptake (4). Thus, these results indicate that current TPN regimens are not as effective as oral nutrition in supporting anabolic processes. The reason for this inefficiency is currently unknown. However, it could be due to the lack of nutrients in the gut lumen during TPN, or the breakdown of the gut mucosa during TPN, or simply the wrong balance of nutrients in the TPN solution. In regard to the latter there are a number of amino acids (eg, glutamine, tyrosine, cysteine, taurine) which are present in oral diets but are not commonly given intravenously, due to insolubility or instability.
Although the measurement of interorgan amino acid fluxes have provided important information about amino acid metabolism during feeding, starvation and following stress it is associated with a number of limitations. The inter- and intra-individual variation in arterovenous difference is quite large. Thus, large groups of individuals are often needed to show significant differences effects of treatments. The flux value is only strictly valid for the instant at which it was measured. Because of this the AV difference technique provides useful information only in individuals whose metabolic and physiological state is stable. This precludes the technique from being useful in patients in the early stages after injury. One has to be fully aware of these limitations if one is use this technique to measure inter-tissue exchange of metabolic substrates.
1. Arora, N. S. and D. F. Rochester. Respiratory muscle strength and maximal voluntary ventilation in undernourished patients. Am. Rev. Respir. Dis. 126: 5-8, 1982.
2. Bessey, P. Q., J. M. Watters, T. T. Aoki, and D. W. Wilmore. Combined hormonal infusion stimulates the metabolic response to injury. Ann. Surg. 200: 264-281, 1984.
3. Douglas, R. G. and J. H. F. Shaw. Metabolic response to sepsis and trauma. Br. J. Surg. 76: 115-122, 1989.
4. Elia, M., P. Folmer, A. Schlatmann, A. Goren, and S. Austin. Carbohydrate, fat, and protien metabolism in muscle and in the whole body after mixed meal ingestion. Metabolism. 37: 542-551, 1988.
5. Elia, M. and A. Kurpad. What is the blood flow to resting human muscle? Clin. Sci. 84: 559-563, 1993.
6. Elia, M. and G. Liversey. Effects of ingested steak and infused leucine on forelimb metabolism in man and the fate of the carbon skeletons and amino groups of branch-chain amino acids. Clin. Sci. 64: 517-526, 1983.
7. Elia, M., G. Neale, and G. Liversey. Alanine and glutamine release from the human forearm: effects of glucose administration. Clin. Sci. 69: 123-133, 1985.
8. Frayn, K. N., J. Khan, S. W. Coppack, and M. Elia. Amino acid metabolism in human subcutaneous adipose tissue in vivo. Clin. Sci. 80: 471-474, 1991.
9. Kee, A. J. and R. C. Smith. Organ clearance of tyrosyl-arginine and its effect on amino acid metabolism in young sheep. Metabolism. 42: 958-966, 1993.
10. Loder, P. B., R. C. Smith, A. J. Kee, S. R. Kohlhardt, M. M. Fisher, M. Jones, and T. S. Reeve. What rate of infusion of intravenous nutrition solution is required to stimulate uptake of amino acids by peripheral tissues in depleted pat ients. Ann. Surg. 211: 360-368, 1990.
11. Lund, P. and D. H. Williamson. Inter-tissue nitrogen fluxes. Br. Med. Bull. 41: 251-256, 1985.
12. Mallette, L. E., J. H. Exton, and C. R. Park. Control of gluconeogenesis from amino acids in the perfused rat liver. J. Biol. Chem. 244: 5713-5723, 1969.
13. Meijer, A. J., W. H. Lamers, and R. A. F. M. Chamuleau. Nitrogen metabolism and ornithine cycle function. Physiol. Rev. 70: 701-748, 1997.
14. Petersson, B., S.-O. Waller, E. Vinnars, and J. Wernerman. Long-term effect of glycyl-glutamine after elective surgery on free amino acids in muscle. J. Parenter. Enteral. Nutr. 18: 320-325, 1994.
15. Rennie, M. J., P. A. MacLennan, H. S. Hundal, B. Weryk, K. Smith, P. M. Taylor, C. Egan, and P. W. Watt. Skeletal muscle glutamine transport, intramuscular glutamine concentration, and muscle-protein turnover. Metabolism. 38: 47-51, 1989 .
16. Snell, K. Muscle alanine synthesis and hepatic gluconeogenesis. Biochem. Soc. Trans. 8: 205-213, 1980.
17. Vinnars, E., F. Hammarqvist, A. Von der Decken, and J. Wernerman. Role of glutamine and its analogs in posttraumatic muscle protein and amino acid metabolism. J. Parenter. Enteral. Nutr. 14: 125S-129S, 1990.
18. Wernerman, J. and E. Vinnars. The effect of trauma and surgery on interorgan fluxes of amino acids in man. Clin. Sci. 73: 129-133, 1987.
19. Wilmore, D. W. Are the metabolic alterations associated with critical illness related to the hormonal environment? Clin. Nutr. 5: 9-19, 1986.
20. Windmueller, H. G. and A. E. Spaeth. Vascular perfusion of rat small intestine: metabolic studies with isolated and in situ preparations. Fed. Proc. 36: 177-181, 1977.
21. Windmueller, H. G. and A. E. Spaeth. Identification of ketone bodies and glutamine as the major respiratory fuels in vivo for postabsorptive rat small intestine. J. Biol. Chem. 253: 69-76, 1978.
22. Windsor, J. A. and G. L. Hill. Weight loss with physiological impairment: a basic indicator of surgical risk. Ann. Surg. 207: 290-296, 1988.
23. Young, V. R., S. D. Alexis, B. S. Baliga, H. N. Munro, and W. Muecke. Metabolism of administered 3- methylhistidine. J. Biol. Chem. 247: 3592-3600, 1972.
ALTERNATIVE FUELS IN THE GASTROINTESTINAL TRACT
Burrin DG. Reeds PJ. Current Opinion in Gastroenterology. 13(2):165-170, 1997 Mar.
MCCOLLUM-AWARD-LECTURE, 1996 - PROTEIN-ENERGY MALNUTRITION IN MAINTENANCE DIALYSIS PATIENTS
Kopple JD. American Journal of Clinical Nutrition. 65(5):1544-1557, 1997 May.
GLUTAMINE AND OTHER AMINO ACID LOSSES DURING CONTINUOUS VENOVENOUS HEMODIAFILTRATION
Novak I. Sramek V. Pittrova H. Rusavy Z. Tesinsky P. Lacigova S. Eiselt M. Kohoutkova L. Vesela E. Opatrny K. Artificial Organs. 21(5):359-363, 1997 May.
METABOLIC SUPPORT OF THE GASTROINTESTINAL TRACT - POTENTIAL GUT PROTECTION DURING INTENSIVE CYTOTOXIC THERAPY
Wilmore DW. Cancer. 79(9):1794-1803, 1997 May 1.
PROINFLAMMATORY CYTOKINES, NUTRITIONAL SUPPORT, AND THE CACHEXIA SYNDROME - INTERACTIONS AND THERAPEUTIC OPTIONS [Review]
Moldawer LL. Copeland EM. Cancer. 79(9):1828-1839, 1997 May 1.
PROTEIN AND ENERGY METABOLISM IN ACUTE RENAL FAILURE
Hirschberg R. Maroni BJ. Seminars in Dialysis. 10(2):74-81, 1997 Mar-Apr.
THE IMPACT OF MAINTENANCE HEMODIALYSIS ON PROTEIN AND ENERGY REQUIREMENTS
Graham KA. Goodship THJ. Seminars in Dialysis. 10(2):82-86, 1997 Mar-Apr.
ADMIXTURE OF A MULTIVITAMIN PREPARATION TO PARENTERAL NUTRITION - THE MAJOR CONTRIBUTOR TO IN VITRO GENERATION OF PEROXIDES
Lavoie JC. Belanger S. Spalinger M. Chessex P. Pediatrics. 99(3):E 61-E 65, 1997 Mar.
PARENTERAL ADMINISTRATION OF DIFFERENT AMOUNTS OF BRANCH-CHAIN AMINO ACIDS IN SEPTIC PATIENTS - CLINICAL AND METABOLIC ASPECTS
Garciadelorenzo A. Ortizleyba C. Planas M. Montejo JC. Nunez R. Ordonez FJ. Aragon C. Jimenez FJ. Critical Care Medicine. 25(3):418-424, 1997 Mar.
A PROSPECTIVE RANDOMIZED STUDY OF GLUTAMINE-ENRICHED PARENTERAL COMPARED WITH ENTERAL FEEDING IN POSTOPERATIVE PATIENTS
Fish J. Sporay G. Beyer K. Jones J. Kihara T. Kennedy A. Apovian C. Jensen GL. American Journal of Clinical Nutrition. 65(4):977-983, 1997 Apr.
PHENYLALANINE REQUIREMENTS DETERMINED BY USING L-[1-C-14]PHENYLALANINE IN NEONATAL PIGLETS RECEIVING TOTAL PARENTERAL NUTRITION SUPPLEMENTED WITH TYROSINE
House JD. Pencharz PB. Ball RO. American Journal of Clinical Nutrition. 65(4):984-993, 1997 Apr.
ACUTE CHANGES IN LEUCINE AND PHENYLALANINE KINETICS PRODUCED BY PARENTERAL NUTRITION IN PREMATURE INFANTS
Clark SE. Karn CA. Ahlrichs JA. Wang JY. Leitch CA. Liechty EA. Denne SC. Pediatric Research. 41(4 Part 1):568-574, 1997 Apr.
TYROSINE KINETICS AND REQUIREMENTS DURING TOTAL PARENTERAL NUTRITION IN THE NEONATAL PIGLET - THE EFFECT OF GLYCYL-L-TYROSINE SUPPLEMENTATION
House JD. Pencharz PB. Ball RO. Pediatric Research. 41(4 Part 1):575-583, 1997 Apr.
NUTRITION IN ACUTE RENAL FAILURE
Riella MC. Renal Failure. 19(2):237-252, 1997.
ALANYLGLUTAMINE-ENRICHED TOTAL PARENTERAL NUTRITION IMPROVES PROTEIN METABOLISM MORE THAN BRANCHED CHAIN AMINO ACID-ENRICHED TOTAL PARENTERAL NUTRITION IN PROTRACTED PERITONITIS
Naka S. Saito H. Hashiguchi Y. Lin MT. Furukawa S. Inaba T. Fukushima R. Wada N. Muto T. Journal of Trauma-Injury Infection & Critical Care. 42(2):183-190, 1997 Feb.
ENTERAL ADMINISTRATION OF ORNITHINE ALPHA-KETOGLUTARATE OR ARGININE ALPHA-KETOGLUTARATE - A COMPARATIVE STUDY OF THEIR EFFECTS ON GLUTAMINE POOLS IN BURN-INJURED RATS
Leboucher J. Coudraylucas C. Lasnier E. Jardel A. Ekindjian OG. Cynober LA. Critical Care Medicine. 25(2):293-298, 1997 Feb.
HEPATIC AMINO ACID AND PROTEIN METABOLISM IN NON-ANORECTIC, MODERATELY CACHECTIC TUMOR-BEARING RATS
Deblaauw I. Deutz NEP. Boers W. Vonmeyenfeldt MF. Journal of Hepatology. 26(2):396-408, 1997 Feb.
THE DIETARY MANAGEMENT OF CROHNS DISEASE [Review]
King TS. Woolner JT. Hunter JO. Alimentary Pharmacology & Therapeutics. 11(1):17-31, 1997 Feb.
COMBINED EFFECTS OF CALORIC RESTRICTION AND BRANCHED-CHAIN AMINO ACID SUPPLEMENTATION ON BODY COMPOSITION AND EXERCISE PERFORMANCE IN ELITE WRESTLERS
Mourier A. Bigard AX. Dekerviler E. Roger B. Legrand H. Guezennec CY. International Journal of Sports Medicine. 18(1):47-55, 1997 Jan.
THE METABOLIC ROLES, PHARMACOLOGY, AND TOXICOLOGY OF LYSINE [Review]
Flodin NW. Journal of the American College of Nutrition. 16(1):7-21, 1997 Feb.
GROWTH HORMONE MODULATES AMINO ACID OXIDATION IN THE SURGICAL PATIENT - LEUCINE KINETICS DURING THE FASTED AND FED STATE USING MODERATE NITROGENOUS AND CALORIC DIET AND RECOMBINANT HUMAN GROWTH HORMONE
Carli F. Webster JD. Halliday D. Metabolism: Clinical & Experimental. 46(1):23-28, 1997 Jan.
THE ROLE OF SUBSTRATES IN THE REGULATION OF PROTEIN METABOLISM [Review]
Tessari P. Barazzoni R. Zanetti M. Kiwanuka E. Tiengo A. Baillieres Clinical Endocrinology & Metabolism. 10(4):511-532, 1996 Oct.
GLUTAMINE DEPLETION AND INCREASED GUT PERMEABILITY IN NONANORECTIC,
NON-WEIGHT-LOSING TUMOR-BEARING RATS
Deblaauw I. Deutz NEP. Vanderhulst RRWW. Vonmeyenfeldt MF. Gastroenterology. 112(1):118-126, 1997 Jan.
GLUTAMINE - FROM BASIC SCIENCE TO CLINICAL APPLICATIONS
Ziegler TR. Szeszycki EE. Estivariz CF. Puckett AB. Leader LM. Nutrition. 12(11-12 Suppl S):S 68-S 70, 1996 Nov-Dec.
PARENTERAL GLUTAMINE SUPPLY IN INTENSIVE CARE PATIENTS
Griffiths RD. Palmer TEA. Jones C. Nutrition. 12(11-12 Suppl S):S 73-S 75, 1996 Nov-Dec.
DEVELOPMENT OF AN INTRAVENOUS GLUTAMINE SUPPLY THROUGH DIPEPTIDE TECHNOLOGY
Langer K. Nutrition. 12(11-12 Suppl S):S 76-S 77, 1996 Nov-Dec.
GLUTAMINE - AN ESSENTIAL AMINO ACID FOR THE GUT
Vanderhulst RRWJ. Vonmeyenfeldt MF. Soeters PB. Nutrition. 12(11-12 Suppl S):S 78-S 81, 1996 Nov-Dec.
A REVIEW OF CURRENT AMINO ACID ESTIMATES FOR SWINE .2. [Review]
Friesen KG. Tokach MD. Nelssen JL. Goodband RD. Compendium on Continuing Education for the Practicing Veterinarian. 18(12):1368 ff., 1996 Dec.
A PARENTERAL NUTRITION REGIMEN WITH ORNITHINE SUBSTITUTED FOR ARGININE ALTERS THE AMINO ACID, BUT NOT POLYAMINE, CONTENT OF THE WARD COLON TUMOR
Grossie VB. Nishioka K. Nutrition & Cancer. 27(1):102-106, 1997.
ON THE USEFULNESS OF GLYCYLGLYCINE IN HEMODIALYSIS AND PERITONEAL DIALYSIS SOLUTIONS [Review]
Yatzidis H. Dombros NV. Digenis GE. ASAIO Journal. 42(6):984-992, 1996 Nov-Dec.
ALANYL-GLUTAMINE-SUPPLEMENTED TOTAL PARENTERAL NUTRITION IMPROVES SURVIVAL AND PROTEIN METABOLISM IN RAT PROTRACTED BACTERIAL PERITONITIS MODEL
Naka S. Saito H. Hashiguchi Y. Lin MT. Furukawa S. Inaba T. Fukushima R. Wada N. Muto T. JPEN 20(6):417-423, 1996
If any readers have interesting nutrition related sites that they would like others to know about please email me the details and I shall include them in the next Newsletter.
fax : +61-3-6231-3145
36, Pregnells Road
SANDFLY, TASMANIA 7150