Malnutrition, Starvation and Refeeding Syndrome

1. Malnutrition, Starvation and Refeeding Syndrome Khursheed Jeejeebhoy

2. Starvation and Semi-starvation • State of Negative Protein-Energy Balance • Absence of nutrient intake • Intake below requirements

3. Metabolic Adaptation to Starvation Post Absorptive state --- Overnight fast after a meal Fast lasting 12-24 Hours Fast lasting > 3days Prolonged Starvation

4. Post-Absorptive State • The Brain Must receive Glucose • Insulin levels fall: • Glucose delivery to Tissues 8-10 g/hr • Increased Glycogenolysis 50% • Continued Gluconeogensis 50% • Lactate and Pyruvate 50% • Amino acids 50% • Muscle uses mainly fatty acids • 2/3 fuel oxidation is derived from fatty acids

5. Fasting ~ 2-4 days • Liver glycogen depleted • Insulin levels fall • Glucose production by Gluconeogenesis: • Lactate and Pyruvate • Amino acids • Nitrogen loss from amino acid is 10-12 g/day • Branched chain aminoacids released by muscle and oxidized • Ketone production increases • Brain reduces glucose utilization and increases Ketone body oxidation

6. Prolonged Starvation • Metabolic rate falls • Nitrogen losses decrease to 4-5 g/day • Brain now uses ketones as the sole source of energy • Muscle uses fatty acid and spares branched-chain amino acid oxidation

7. Clinical Effects of Starvation • Resting Energy Expenditure fall by about 25-35% by 3 weeks • Serum Albumin Concentrations remain normal • Serum Prealbumin falls • Death occurs when body fat is depleted • Obese persons can withstand prolonged starvation

8. Clinical effects of Fasting: Weight loss

10. Weight and Sodium loss • Fall in insulin level reduces sodium reabsorption by the kidney • Increased sodium excretion • Diuresis • Reduced sodium intake increases negative sodium balance • Water loss main cause of rapid weight loss seen early in starvation

11. Malnutrition • Malnutrition is a condition in which there is unbalanced deficiency of nutrients. • Causes are: • Macronutrient deficiency • Protein-energy malnutrition • Protein deficiency • Energy deficiency • Micronutrient deficiency • Electrolyte • Potassium • Magnesium • Phosphorus • Trace element • Zinc • Copper • Chromium • Selenium • Vitamin Deficiency • Fat soluble - Vitamin D • Water soluble - Thiamine

12. Protein-Energy MalnutritionReduced intake of both Protein and energy • 1944-46 32 volunteers reduced their intake from 2400 kcals/d to 1600 kcals/day (Keys Minnesota study) • Lost 70% body fat and 24% FFM • New equilibrium at 24 weeks into the diet.

13. PEM: Nitrogen adaptation Martin and Robison 1922 Neg N balance Pos. N balance

14. Nitrogen Adaptation • Loss of labile nitrogen pool reduces nitrogen output • Equilibrium restored unless protein intake fall below < 37 mg/Kg/day on a diet meeting energy requirements

15. Energy Adaptation • Body reduces energy requirements by: • Reduced metabolic rate of the body cell mass. • Reduced body cell mass. • Body weight equilibrates approximately at: • 28-30 kcal/kg/day

16. Hormonal response • Insulin levels fall promoting release of glucose and free fatty acids for energy • T3 levels reduced resulting in a lower metabolic rate • IGF -1 levels fall with starvation reducing protein synthesis

17. Hypoproteinemia • Low prealbumin levels can be due to: • Protein deficiency • Protein loss • Acute Phase reaction • Low Albumin levels are: • ?Low protein with high energy intake • Protein loss • Acute Phase reaction • Hypoalbuminemia is a sign of disease not malnutrition

18. Micronutrient deficiency • Iron deficiency: • Blood loss due to disease • Dietary deficiency • intake of cereal iron (India) • Magnesium Deficiency • Dietary – Alcoholism • Renal • Endocrine metabolic • Malabsorption • Short Bowel • Iatrogenic • Phosphorus deficiency • Iatrogenic • Alcoholism • Recovery from diabetic ketoacidosis • Zinc Deficiency • Iatrogenic • Gastrointestinal losses • Copper Deficiency • Infants recovering from malnutrition • Iatrogenic • Vitamin D deficiency • Dietary • Malabsorption • Lack of sun exposure

19. Micronutrient deficiency • Vitamin A deficiency • Dietary deficiency in developing countries • Iatrogenic • Thiamine deficiency • Alcoholism • Iatrogenic • Diuretics • Folate deficiency • Alcoholism • Malabsorption • Vitamin B12 Deficiency • Vegans • Malabsorption • Poor intake in an ageing population

20. Refeeding Syndrome • Refeeding a malnourished patient results in: • Rise of insulin levels • Sodium and water retention • Potassium retention • Phosphorus retention • Magnesium retention • Refeeding may cause serious: • Hypokalemia • Hypophosphatemia

21. Refeeding Syndrome • Refeeding a malnourished patient can result in Heart failure due to: • Atrophic myocardium in malnutrition • Muscle depletion of Mg, K, P • Sodium and water overload • Increased metabolic rate

24. REFEEDING EDEMA: CARDIAC FAILURE 36 year old Anorexia fed by NG 3200 kcal/d

25. Micronutrient DeficienciesIn Malnutrition and the Heart MICRONUTRIENTSYNDROME Thiamine deficiency Heart Failure Magnesium Deficiency Arrhythmias Phosphorus Deficiency Cardiomyopathy Selenium Deficiency Cardiomyopathy Potassium Deficiency Arrhythmias Myocardial injury

26. Refeeding Syndrome • High CHO intake exacerbates the refeeding syndrome • Low protein High energy diet causes fat gain but not lean tissue • High protein diet can reduce nitrogen loss even if energy deficient • Exercise important to regain muscle mass

29. Relationship of Protein and Energy to Nitrogen retention Energy intake kcal/d

30. Refeeding SyndromeJournal of Internal Medicine 2005; 257: 461–468 • Case controlled study in Geriatric ward • 325 had hypophosphatemia • 326 normal plasma phosphorus levels

31. Refeeding SyndromeJournal of Internal Medicine 2005; 257: 461–468

32. Refeeding SyndromeJournal of Internal Medicine 2005; 257: 461–468

33. Refeeding SyndromeAm J Clin Nutr 1979;32:981-91 • Severely starved men fed: 27 g/day protein + 2250 Kcal/d • Weight gain • Increased Cholesterol • Albumin levels fell • Nitrogen balance 0 • Protein intake increased to 100 g/day • Positive nitrogen balance • Rise in serum albumin

34. Refeeding SyndromeAm J Clin Nutr 1979;32:981-91 • Refeeding of malnourished patients: • 20 kcal/kg/day and 1.5-2.0 g/protein/day • Low CHO and higher fat • Monitor K, P, Mg and weight gain • Diuretics if rquired • Gradually increase energy intake depending on response.