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Advanced Clinical Immuno Nutrition & Its Application Soly James Chief Dietician S.L.Raheja hospital-A Fortis Associate Mahim, Mumbai A high proportion of patients in hospital are malnourished and that malnourishment impairs immune function. The capacity for nutrients to modulate the actions of the immune system and, to affect clinical outcome has thus become an important issue in clinical practice. (McWhirter & Pennington, 1994) Immunonutrition Immunonutrition is defined as modulation of the activities of the immune activation by nutrients or specific food items fed in amounts above those normally encountered in the diet Immunomodulatory substance interfere with 3 basic area of the immune responses directly or indirectly; (i) the mucosal barrier function (ii) the cellular defence function and (iii) the local or systemic inflammatory response Conditions associated with low immunity Trauma (Accidents & Burns) Illness & Stress Post Operative complication Surgery Cancer Critically ill Trauma , surgery & critically ill Stress response Glycolysis, Lipolysis Proteolysis Auto-catabolism Pro-inflammatory cascades Immuno-suppression Induce hormonal, metabolic & inflammatory changes Peripheral Blood Mononuclear Cell Key Processes Initiated by secretion of the pro-inflammatory cytokines interleukin (IL) 1, IL-6 and Tumour Necrosis Factor (TNF) α. (1) creation of a hostile environment (for pathogens); (2) provision of nutrients for the immune system from endogenous sources; (3) strengthening of the protective and control systems against damage to healthy tissue by the immune response (Grimble, 1998a) Trauma and infection and burn Immunonutrition Immune system activation Pro-inflammatory cytokines (IL1&6, TNF) T& B Cells glucose Immunonutrients (glutamine) Nutrient release from host tissue S amino acid Acute phase protein synthesis Glutathione synthesis Antioxidant defense strengthened How can we enhance the Immunity? Omega-3 fatty acids (PUFA-3) “Conditionally Essential” amino acids ◦ Arginine ◦ Glutamine Nucleotides S. D. Heys et al Nutr. Hosp. (2004) XIX (6) 325-332 (Grimble,1998a; O.Flaherty & Bouchier Hayes, 1999) IMF in the Critical Care… Review of 26 studies (surgical, trauma, burn, mixed population) ◦ ◦ ◦ ◦ ◦ ◦ ◦ Decreased infection rate: Intra-abdominal abscess (74% reduction) Nosocomial pneumonia (46% reduction) Wound infections (54% reduction) 2.25 less vent days 1.6 less ICU days 3.4 less hospital days reduces significantly the rate of severe mucosal toxicity during concomitant chemoradiotherapy for advanced local-regional squamous cell carcinomas of the head and neck. Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings Montejo, Clinical Nutrition, 2003, Kenneth A. Kudsk Annu. Rev. Nutr. 2006 Omega 3 Fatty Acids Clinical data Biochemical data • Inflammatory response Cardiac arrhythmias Tissue microperfusion Graft function Cancer in cell lines Limits omega-6 immune suppression • Maturation of CNS • Clearance • • • • • • Biological regulators • Cell membrane structure and function • Influences membrane fluidity • Alters receptors activity • Eicosanoid metabolism • Cytokine production • Gene expression Intensive Care Med. 2008 Nov;34(11):1980-90. Crit Care. 2009;13(3):305. L-Arginine L-arginine is converted in the body into a chemical called nitric oxide. ◦ Vasodilator ◦ Stimulates the release of growth hormone & insulin Improves recovery after surgery ◦ L-arginine with RNA and EPA reduce the recovery time reduce infections improve wound healing Improves immune system in people with head and neck cancer Improves helper T-cell numbers (lymphocyte proliferation) American Journal of Critical Care. 2004 Heyland DK al (2001) JAMA 286, Glutamine One of the 20 amino acids Glutamine is a nonessential amino acid, which becomes “conditionally essential” during periods of catabolic stress When the body is stressed, it releases high levels of hormone cortisol into the bloodstream which can lower the body's stores of glutamine Buchman AL, Am J Clin Nutr, 2001 Why Glutamine? • During stress- drastic reduction in the glutamine level (more than 50%) • Requirement increases in critical illness • Synthesis rate is very less • Demand increases but rate of synthesis does not increase • Only BCAA – is not sufficient because synthesis of glutamine from BCAA is limited • Normal Diet might provide 3-5 gms glutamine/day GLN Therapy GI Tract Major source of energy for enterocytes Supports nucleotide biosynthesis May protect epithelial cells against endotoxin Enhances HSP expression post stress Immune Cell function Kidney Acid Muscle Lungs Major source of energy for proliferating cells Supports neutrophil killing & macrophage function Enhances HSP expression post stress Vital for appropriate cytokine secretion base regulation NH3 metabolism Increase protein synthesis Major source of energy for endothelial cells May protect epithelial cells against endotoxin Enhances HSP expression post stress Glutamine & Cancer Chemotherapy Mucositis, Stomatitis, Enterocolitis, Bacterial translocation, Endotoximia Radiotherapy Abdominal pain, bloody diarrhea, malabsorption and bacterial translocation because of… - Destruction of crypt cells - Decreased villous height - Ulceration - Necrosis of GI epithelium Glutamine and cancer. J Nutr. 2001;131 Clin J Oncol Nurs, 2002 Glutamine Dosage Clinical Condition Dosage Critical condition 0.57 g / kg bw /day Before chemotherapy/radiation treatment During chemotherapy/radiation treatment BMT 5-10 g / day Paediatric oncology 0.65 gm /kg bw/day 20-30 g /day 20-30 g /day Contraindications • End stage liver diseases • End stage kidney diseases • Elderly people who have decreased kidney function Dietary Nucleotides Building blocks for DNA and RNA. Conditionally essential in stressed states Improves T-cell function Required for almost all cell activity and growth Essential for rapidly replicating cells to help support immune function Benefits of supplementation: Protein synthesis Liver recovery Digestion Intestinal repair When to feed an IMF? Immune Modulating Formulations (supplemented with agents such as arginine, glutamine, nucleic acid, omega-3 fatty acids, and antioxidants) should be used for the appropriate patient population (major elective surgery, trauma, burns, head and neck cancer, and critically ill patients on mechanical ventilation), being cautious in patients with severe sepsis (Grade A). SCCM/ASEPN Critical Care Nutrition Guidelines, 2009 (Cowley et al. 1996; Arnalich et al. 2000). Pharmaconutrients can positively or negatively effect clinical outcome just as any other pharmacologic agent would Administer the right nutrients, in the right amounts, at the right time Thank You… ZINC:3mg (as Zinc Sulphate monohydrate) A critical element Small deficiency is a disaster. Role in tissue repair. Helps the body use carbohydrate, protein, and fat. Helps to maintain proper immune function, including promoting wound healing. Maintaining a sense of taste and smell. Maintaining normal vitamin A levels and usage. SELENIUM: 15mcg (as L-Selenomethionine) • Essential trace mineral required for normal human health and reproduction. • Needed by certain enzymes that help with normal body functions. • Aids in protein synthesis, and enhances fertility and growth and development. • An anti-oxidant-thus helps protect the body from damaging effects of free radicals. • May also prevent or slow tumor growth.