Lect16 Pcm

Protein Calorie Malnutrition

Protein-Calorie Malnutrition PCM affects ~ 1 billion individuals world-wideIn US, 30-50% of patients will be malnourished at admission to hospital69% will have a decline in nutrition status during hospitalization 25-30% will become malnourished during hospitalization

Malnutrition in Hospitalized PtsConsequences for hospitalized pts:poor wound healinghigher rate of infectionsgreater length of staygreater costsIncreased morbidity and mortality

DefinitionsFast: exclusion of all food energyStarvation: prolonged inadequate intake of protein and/or energyCachexia: wasting induced by metabolic stress

Brief Review of Fed StateExogenous fuel utilizationAbsorption of glucose and amino acids stimulates insulin secretionDeposition of nutrients in tissueGlucose: glycogen, triglyceride synthesisAmino Acids: protein synthesis, mainly in muscle

Fuels in Fed StateGlucose-dependent: brain, blood cells and renal medullaBrain uses 50% of available glucosePreferential users of glucose: heart, renal cortex and skeletal muscleFatty acids: liverProtein/AA: not used as fuels unless excessive intake

Postabsorptive StateFed state ends when last nutrient is absorbed, body switches to endogenous fuel utilizationDecrease level of insulin, increase in glucagonRelease, transfer and oxidation of fatty acidsRelease of glucose from liver glycogenRelease of free amino acids from muscle as a source of fuel

Progression of FastingNormal post-absorptive state: 12 hoursDraw on short term reserves to maintain blood glucose levels for glucose-dependent tissues (brain, blood cells, and renal medulla)release and oxidation of fatty acidsrelease of glucose from liver glycogenLiver glycogen capacity: approximately 1000 kcal Equivalent to 250g carbohydrate/glucose

Fast Longer than 24 hoursFurther decrease in insulin, increase in glucagonProteolysis and release of amino acids from muscle as a source of fuelActivation of hormone sensitive lipaseincrease in lipolysisincrease in circulating FFA and TGGluconeogenesis increases

GluconeogenesisCori cycle in Liver glucose --> converted to lactate/pyruvate in skeletal muscle (anaerobic)-->travels back to liver for conversion to glucose

GluconeogenesisGlucose-Alanine Cycle: LiverAA deaminated in muscle C-skeleton used for energy -->pyruvate and NH2 --> alaninealanine returns to liver for deaminationNH2 -->urea for excretionpyruvate --> glucose via GNG

GluconeogenesisGlutamine cycle in KidneyMuscle glutamine --> kidney --> glutamate + NH3 -->a-ketoglutarate --> glucose

Kidney is initially a minor source, over time increases to supply up to 50% of glucose

Fast longer than 2-3 daysGNG ongoing, sources of substrate: endogenous glycerolalanine and glutamine from musclelactate and pyruvateKetosis

Fast longer than 2-3 daysKetosischaracterized by presence of ketone bodiesacetoacetate, acetone, b-hydroxybutyrate byproduct of fatty acid oxidation in livercan be used by all tissues with mitochondriautilized by brain, decreasing glucose consumption by 25%Can be prevented by providing 150g glucose per day

Long Term Starvation (>7-10d)Decreased metabolic ratedecreased activity, body temperatureConservation of proteindecrease in muscle pro breakdown from 75g to 20 g per dayIncreased fatty acid oxidationLiver, heart and muscle use ketone bodies

Long Term Starvation (>7-10d)Decreased glucose availabilityBrain:fed state: uses 75% (140g/day), completely oxidized>3 week of fast: replace 50% of glucose with ketonesdecreased complete oxidation, recycles via GNGBlood cells/Renal medullaanaerobic glycolysis to pyruvate and lactate

Origin of blood glucose:(I) Exogenous; (II) Glycogen, Liver gluconeogenesis; (III) Liver gluconeogenesis, Glycogen; (IV & V)Liver and Kidney gluconeogenesis

Major fuel of brain:(I) - (III) Glucose; (IV) Glucose, ketone bodies;(V) Ketone bodies, glucose

Minnesota study (1944-1946)32 young, healthy volunteers consumed 2/3 of normal energy intake (1600 kcal) for 24 weeks wt loss of 23% of body weightloss of 70% of fat massloss of 24% of lean body masswt loss alone underestimated loss of body mass due to increase in edema

Minnesota study (1944-1946)Decrease in metabolic rate by 40%corresponds to decreased in food energycorrelates to loss of lean body massreduced per unit of remaining LBMlower thermal effect of food due to smaller mealsdecrease in physical activityachieve new energy balance

StarvationFunctional alterationshormonal changesdecreased thyroid fx --> decreased BMRdecreased gonadotropinsdecreased somatomedins --> decreased muscle/cartilage synthesis, decreased growthdecreased metabolic rate and caloric needdecreased body tempdecreased activity, increased sleep

StarvationChanges in Organ FunctionGI tract - loss of mass, decreased villi and cryptsdecreased enzyme secretionimpaired motilitytendency for bacterial overgrowthmaldigestion and malabsorption

StarvationChanges in Organ FunctionLiver: loss of massdecreased protein synthesisperiportal fat accumulation (fatty liver)hepatic insufficiencySkeletal musclecatabolized for GNG - decreased massutilization of ketones: slower contractionsdiminished function: intercostal muscles - decreased respiratory function

StarvationChanges in Organ FunctionCardiovascular systemdecreased cardiac outputbradycardia, hypotensiondilatation, degeneration, fibrosiscentral circulation takes precedence, leads to postural hypotensionRespiratory system: decreased cilia, reduced bacterial clearancedecreased deep breathing

StarvationChanges in Organ FunctionKidneydecreased perfusion, decreased GFRincreased GNGincreased NH4 excretionImmune functiondecreased T-lymphocyte countdecreased cytokine activityanergyincreased infection rate (pneumonia)

StarvationChanges in Organ FunctionNervous system:decrease in nerve myelinationdecrease brain growth

Successful AdaptationGoals:1. Maintain glucose homeostasis and conserve glucose pool.2. Preserve structural and functional lipids and proteins3. Preserve the organismPreferential visceral uptake of AA released by peripheral tissue

Failed adaptationMetabolic disease: hyperthyroidism/thyroid storm, insulinomaMicronutrient deficiency - mineral deficiency interferes with protein sparingFood restriction too severeMetabolic stressors such as infection, surgery lead to hypermetabolic state

Hypermetabolic State and CachexiaWounds, surgical stress, cancer, inflammatory conditions and infectionIncreased production of cortisol, interleukins, TNFhypercatabolic state with increased RMR = increased energy requirementsInsulin resistance, hyperglycemia - no starvation adaptation, poor utilization of stubstrateProtein breakdown continues unabatedIn some burn patients amount of protein catabolized can reach 200 g/d = ~0.5 lb/day lean body mass! Severe protein malnutrition results in as little as 1 week.Repletion of body stores is not achievable until metabolic stressor has been resolved

PCM: Clues to Cause From Body Composition AnalysisEnergy depletion (reduced fat stores) out of proportion to LBM loss:Starvation = MarasmusPredominant protein depletion (reduced LBM):Cachexia = KwashiorkorCombined (Marasmic Kwashiorkor):Most common PCM seen in hospitalized patients

PCM Marasmus in Hospitalized PatientsSevere Energy Depletion: Temporal wasting observed with ageing and reduced intake

PCM Marasmus in Hospitalized PatientsSevere Energy Depletion: Loss of Skinfold Thickness

Nutrition AssessmentHospital or Clinic ScreeningIdentifying and treating malnutrition Preventing Hospital-Acquired Malnutrition

Assessing nutrition risk on admission: JCAHO-mandated database

more to come...

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