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 Malnutrition Reduced 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 Deficiencies In 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 Syndrome Refeeding Syndrome Journal of Internal Medicine 2005; 257: 461–468  Case controlled study in Geriatric ward  325 had hypophosphatemia  326 normal plasma phosphorus levels

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

33. Refeeding Syndrome Am 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 Syndrome Am 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.