Malnutrition, Starvation and Malnutrition, Starvation and Refeeding Syndrome Refeeding Syndrome

Khursheed JeejeebhoyKhursheed Jeejeebhoy

Starvation and Semi-starvationStarvation and Semi-starvation

State of Negative Protein-Energy BalanceState of Negative Protein-Energy Balance– Absence of nutrient intakeAbsence of nutrient intake– Intake below requirementsIntake below requirements

Metabolic Adaptation to StarvationMetabolic Adaptation to Starvation

Post Absorptive state --- Overnight fast after a meal

Fast lasting 12-24 Hours

Fast lasting > 3days

Prolonged Starvation

Post-Absorptive StatePost-Absorptive State

The Brain Must receive GlucoseThe Brain Must receive Glucose Insulin levels fall:Insulin levels fall: Glucose delivery to Tissues 8-10 g/hrGlucose delivery to Tissues 8-10 g/hr

– Increased Glycogenolysis 50%Increased Glycogenolysis 50%– Continued Gluconeogensis 50%Continued Gluconeogensis 50%

Lactate and Pyruvate 50%Lactate and Pyruvate 50% Amino acids 50%Amino acids 50%

Muscle uses mainly fatty acidsMuscle uses mainly fatty acids– 2/3 fuel oxidation is derived from fatty acids2/3 fuel oxidation is derived from fatty acids

Fasting ~ 2-4 daysFasting ~ 2-4 days Liver glycogen depletedLiver glycogen depleted Insulin levels fallInsulin levels fall Glucose production by Gluconeogenesis:Glucose production by Gluconeogenesis:

– Lactate and PyruvateLactate and Pyruvate– Amino acidsAmino acids

Nitrogen loss from amino acid is 10-12 g/dayNitrogen loss from amino acid is 10-12 g/day Branched chain aminoacids released by muscle Branched chain aminoacids released by muscle

and oxidizedand oxidized Ketone production increasesKetone production increases Brain reduces glucose utilization and increases Brain reduces glucose utilization and increases

Ketone body oxidationKetone body oxidation

Prolonged StarvationProlonged Starvation

Metabolic rate fallsMetabolic rate falls Nitrogen losses decrease to 4-5 g/dayNitrogen losses decrease to 4-5 g/day Brain now uses ketones as the sole source Brain now uses ketones as the sole source

of energyof energy Muscle uses fatty acid and spares Muscle uses fatty acid and spares

branched-chain amino acid oxidationbranched-chain amino acid oxidation

Clinical Effects of StarvationClinical Effects of Starvation

Resting Energy Expenditure fall by about Resting Energy Expenditure fall by about 25-35% by 3 weeks25-35% by 3 weeks

Serum Albumin Concentrations remain Serum Albumin Concentrations remain normalnormal

Serum Prealbumin fallsSerum Prealbumin falls Death occurs when body fat is depletedDeath occurs when body fat is depleted Obese persons can withstand prolonged Obese persons can withstand prolonged

starvationstarvation

Clinical effects of Fasting: Clinical effects of Fasting: Weight lossWeight loss

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Weight and Sodium lossWeight and Sodium loss

Fall in insulin level reduces sodium Fall in insulin level reduces sodium reabsorption by the kidneyreabsorption by the kidney– Increased sodium excretionIncreased sodium excretion– DiuresisDiuresis

Reduced sodium intake increases negative Reduced sodium intake increases negative sodium balancesodium balance

Water loss main cause of rapid weight loss Water loss main cause of rapid weight loss seen early in starvationseen early in starvation

MalnutritionMalnutrition Malnutrition is a condition in which there is unbalanced deficiency of nutrients.Malnutrition is a condition in which there is unbalanced deficiency of nutrients. Causes are:Causes are:

– Macronutrient deficiencyMacronutrient deficiency Protein-energy malnutritionProtein-energy malnutrition Protein deficiencyProtein deficiency Energy deficiencyEnergy deficiency

– Micronutrient deficiencyMicronutrient deficiency Electrolyte Electrolyte

– PotassiumPotassium– MagnesiumMagnesium– PhosphorusPhosphorus

Trace elementTrace element– ZincZinc– CopperCopper– ChromiumChromium– SeleniumSelenium

Vitamin DeficiencyVitamin Deficiency– Fat soluble - Vitamin DFat soluble - Vitamin D– Water soluble - ThiamineWater soluble - Thiamine

Protein-Energy MalnutritionProtein-Energy MalnutritionReduced intake of both Protein and energyReduced intake of both Protein and energy

1944-46 32 volunteers reduced their intake 1944-46 32 volunteers reduced their intake from 2400 kcals/d to 1600 kcals/day (Keys from 2400 kcals/d to 1600 kcals/day (Keys Minnesota study)Minnesota study)

Lost 70% body fat and 24% FFMLost 70% body fat and 24% FFM New equilibrium at 24 weeks into the diet.New equilibrium at 24 weeks into the diet.

PEM: Nitrogen adaptation PEM: Nitrogen adaptation Martin and Robison 1922Martin and Robison 1922

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Nitrogen AdaptationNitrogen Adaptation

Loss of labile nitrogen pool reduces nitrogen Loss of labile nitrogen pool reduces nitrogen outputoutput

Equilibrium restored unless protein intake fall Equilibrium restored unless protein intake fall below < 37 mg/Kg/day on a diet meeting below < 37 mg/Kg/day on a diet meeting energy requirementsenergy requirements

Energy AdaptationEnergy Adaptation

Body reduces energy requirements by:Body reduces energy requirements by:– Reduced metabolic rate of the body cell mass.Reduced metabolic rate of the body cell mass.– Reduced body cell mass.Reduced body cell mass.

Body weight equilibrates approximately at:Body weight equilibrates approximately at:– 28-30 kcal/kg/day28-30 kcal/kg/day

Hormonal response Hormonal response

Insulin levels fall promoting release of Insulin levels fall promoting release of glucose and free fatty acids for energyglucose and free fatty acids for energy

T3 levels reduced resulting in a lower T3 levels reduced resulting in a lower metabolic ratemetabolic rate

IGF -1 levels fall with starvation reducing IGF -1 levels fall with starvation reducing protein synthesisprotein synthesis

HypoproteinemiaHypoproteinemia Low prealbumin levels can be due to:Low prealbumin levels can be due to:

– Protein deficiencyProtein deficiency– Protein lossProtein loss– Acute Phase reactionAcute Phase reaction

Low Albumin levels are:Low Albumin levels are:– ?Low protein with high energy intake?Low protein with high energy intake– Protein lossProtein loss– Acute Phase reactionAcute Phase reaction

Hypoalbuminemia is a sign of disease not Hypoalbuminemia is a sign of disease not malnutritionmalnutrition

Micronutrient deficiencyMicronutrient deficiency Iron deficiency:Iron deficiency:

– Blood loss due to diseaseBlood loss due to disease– Dietary deficiency Dietary deficiency

intake of cereal iron (India)intake of cereal iron (India) Magnesium DeficiencyMagnesium Deficiency

– Dietary – AlcoholismDietary – Alcoholism– Renal Renal – Endocrine metabolic Endocrine metabolic – MalabsorptionMalabsorption– Short BowelShort Bowel– IatrogenicIatrogenic

Phosphorus deficiency – Iatrogenic– Alcoholism– Recovery from diabetic ketoacidosis

Zinc DeficiencyZinc Deficiency– IatrogenicIatrogenic– Gastrointestinal lossesGastrointestinal losses

Copper DeficiencyCopper Deficiency– Infants recovering from malnutritionInfants recovering from malnutrition– IatrogenicIatrogenic

Vitamin D deficiencyVitamin D deficiency– DietaryDietary– MalabsorptionMalabsorption– Lack of sun exposureLack of sun exposure

Micronutrient deficiencyMicronutrient deficiency Vitamin A deficiencyVitamin A deficiency

– Dietary deficiency in developing countriesDietary deficiency in developing countries– IatrogenicIatrogenic

Thiamine deficiencyThiamine deficiency– AlcoholismAlcoholism– IatrogenicIatrogenic– DiureticsDiuretics

Folate deficiencyFolate deficiency– AlcoholismAlcoholism– MalabsorptionMalabsorption

Vitamin B12 DeficiencyVitamin B12 Deficiency– VegansVegans– MalabsorptionMalabsorption– Poor intake in an ageing populationPoor intake in an ageing population

Refeeding SyndromeRefeeding Syndrome

Refeeding a malnourished patient results in:Refeeding a malnourished patient results in:– Rise of insulin levelsRise of insulin levels

Sodium and water retentionSodium and water retention Potassium retentionPotassium retention Phosphorus retentionPhosphorus retention Magnesium retentionMagnesium retention

Refeeding may cause serious:Refeeding may cause serious:– HypokalemiaHypokalemia– HypophosphatemiaHypophosphatemia

Refeeding SyndromeRefeeding Syndrome

Refeeding a malnourished patient can result Refeeding a malnourished patient can result in Heart failure due to:in Heart failure due to:– Atrophic myocardium in malnutritionAtrophic myocardium in malnutrition– Muscle depletion of Mg, K, PMuscle depletion of Mg, K, P– Sodium and water overloadSodium and water overload– Increased metabolic rateIncreased metabolic rate

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Heymsfiled In Heart Diseases 1988

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Heymsfield In Heart Disease 1988

Heymsfield In Heart Disease 1988

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

Micronutrient DeficienciesMicronutrient DeficienciesIn Malnutrition and the HeartIn Malnutrition and the Heart

MICRONUTRIENT SYNDROMEThiamine deficiency Heart Failure Magnesium Deficiency ArrhythmiasPhosphorus Deficiency CardiomyopathySelenium Deficiency CardiomyopathyPotassium Deficiency Arrhythmias

Myocardial injury

Refeeding SyndromeRefeeding Syndrome

High CHO intake exacerbates the refeeding High CHO intake exacerbates the refeeding syndromesyndrome

Low protein High energy diet causes fat gain Low protein High energy diet causes fat gain but not lean tissuebut not lean tissue

High protein diet can reduce nitrogen loss High protein diet can reduce nitrogen loss even if energy deficienteven if energy deficient

Exercise important to regain muscle massExercise important to regain muscle mass

Relationship of Protein and Energy to Relationship of Protein and Energy to Nitrogen retentionNitrogen retention

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

Case controlled study in Geriatric wardCase controlled study in Geriatric ward 325 had hypophosphatemia325 had hypophosphatemia 326 normal plasma phosphorus levels326 normal plasma phosphorus levels

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

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

Refeeding SyndromeRefeeding SyndromeAm J Clin Nutr 1979;32:981-91Am J Clin Nutr 1979;32:981-91

Severely starved men fed: 27 g/day protein Severely starved men fed: 27 g/day protein + 2250 Kcal/d+ 2250 Kcal/d

Weight gainWeight gain– Increased CholesterolIncreased Cholesterol– Albumin levels fellAlbumin levels fell– Nitrogen balance 0Nitrogen balance 0

Protein intake increased to 100 g/dayProtein intake increased to 100 g/day– Positive nitrogen balancePositive nitrogen balance– Rise in serum albuminRise in serum albumin

Refeeding SyndromeRefeeding SyndromeAm J Clin Nutr 1979;32:981-91Am J Clin Nutr 1979;32:981-91

Refeeding of malnourished patients:Refeeding of malnourished patients:– 20 kcal/kg/day and 1.5-2.0 g/protein/day20 kcal/kg/day and 1.5-2.0 g/protein/day– Low CHO and higher fatLow CHO and higher fat– Monitor K, P, Mg and weight gainMonitor K, P, Mg and weight gain– Diuretics if rquiredDiuretics if rquired– Gradually increase energy intake depending on Gradually increase energy intake depending on

response.response.