Protein Calorie Malnutrition

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Protein Calorie Malnutrition
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Protein-Calorie Malnutrition

• PCM affects 1 billion individuals world-wide
• In US, 30-50 of patients will be malnourished
  at admission to hospital
• 69 will have a decline in nutrition status
  during hospitalization
• 25-30 will become malnourished during
  hospitalization

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Malnutrition in Hospitalized Pts

• Consequences for hospitalized pts
• poor wound healing
• higher rate of infections
• greater length of stay
• greater costs
• Increased morbidity and mortality

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Definitions

• Fast exclusion of all food energy
• Starvation prolonged inadequate intake of
  protein and/or energy
• Cachexia wasting induced by metabolic stress

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Brief Review of Fed State

• Exogenous fuel utilization
• Absorption of glucose and amino acids stimulates
  insulin secretion
• Deposition of nutrients in tissue
• Glucose glycogen, triglyceride synthesis
• Amino Acids protein synthesis, mainly in muscle

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Fuels in Fed State

• Glucose-dependent brain, blood cells and renal
  medulla
• Brain uses 50 of available glucose
• Preferential users of glucose heart, renal
  cortex and skeletal muscle
• Fatty acids liver
• Protein/AA not used as fuels unless excessive
  intake

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Postabsorptive State

• Fed state ends when last nutrient is absorbed,
  body switches to endogenous fuel utilization
• Decrease level of insulin, increase in glucagon
• Release, transfer and oxidation of fatty acids
• Release of glucose from liver glycogen
• Release of free amino acids from muscle as a
  source of fuel

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Progression of Fasting

• Normal post-absorptive state 12 hours
• Draw on short term reserves to maintain blood
  glucose levels for glucose-dependent tissues
  (brain, blood cells, and renal medulla)
• release and oxidation of fatty acids
• release of glucose from liver glycogen
• Liver glycogen capacity approximately 1000 kcal
• Equivalent to 250g carbohydrate/glucose

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Fast Longer than 24 hours

• Further decrease in insulin, increase in glucagon
• Proteolysis and release of amino acids from
  muscle as a source of fuel
• Activation of hormone sensitive lipase
• increase in lipolysis
• increase in circulating FFA and TG
• Gluconeogenesis increases

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Gluconeogenesis

• Cori cycle in Liver
• glucose --gt converted to lactate/pyruvate in
  skeletal muscle (anaerobic)--gttravels back to
  liver for conversion to glucose

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Gluconeogenesis

• Glucose-Alanine Cycle Liver
• AA deaminated in muscle
• C-skeleton used for energy --gtpyruvate and NH2
  --gt alanine
• alanine returns to liver for deamination
• NH2 --gturea for excretion
• pyruvate --gt glucose via GNG

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Gluconeogenesis

• Glutamine cycle in Kidney
• Muscle glutamine --gt kidney --gt glutamate NH3
  --gta-ketoglutarate --gt glucose
• Kidney is initially a minor source, over time
  increases to supply up to 50 of glucose

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Fast longer than 2-3 days

• GNG ongoing, sources of substrate
• endogenous glycerol
• alanine and glutamine from muscle
• lactate and pyruvate
• Ketosis

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Fast longer than 2-3 days

• Ketosis
• characterized by presence of ketone bodies
• acetoacetate, acetone, b-hydroxybutyrate
• byproduct of fatty acid oxidation in liver
• can be used by all tissues with mitochondria
• utilized by brain, decreasing glucose consumption
  by 25
• Can be prevented by providing 150g glucose per
  day

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Fast longer than 2-3 days

• Significant protein loss during first 7-10 days
• Body protein losses
• 10-12 g urinary N/day
• 360 g LBM per day initially
• 1-2 kg LBM over first 7 days
• Lethal depletion after 3 weeks if no adaptation
  occurs - by the end of 2-3 weeks, decrease muscle
  protein catabolism to lt1/3 of initial (not yet
  understood)

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Long Term Starvation (gt7-10d)

• Decreased metabolic rate
• decreased activity, body temperature
• Conservation of protein
• decrease in muscle pro breakdown from 75g to 20 g
  per day
• Increased fatty acid oxidation
• Liver, heart and muscle use ketone bodies

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Long Term Starvation (gt7-10d)

• Decreased glucose availability
• Brain
• fed state uses 75 (140g/day), completely
  oxidized
• gt3 week of fast replace 50 of glucose with
  ketones
• decreased complete oxidation, recycles via GNG
• Blood cells/Renal medulla
• anaerobic glycolysis to pyruvate and lactate

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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
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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 weight
• loss of 70 of fat mass
• loss of 24 of lean body mass
• wt loss alone underestimated loss of body mass
  due to increase in edema

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Minnesota study (1944-1946)

• Decrease in metabolic rate by 40
• corresponds to decreased in food energy
• correlates to loss of lean body mass
• reduced per unit of remaining LBM
• lower thermal effect of food due to smaller meals
• decrease in physical activity
• achieve new energy balance

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Starvation

• Functional alterations
• hormonal changes
• decreased thyroid fx --gt decreased BMR
• decreased gonadotropins
• decreased somatomedins --gt decreased
  muscle/cartilage synthesis, decreased growth
• decreased metabolic rate and caloric need
• decreased body temp
• decreased activity, increased sleep

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Starvation

• Changes in Organ Function
• GI tract - loss of mass, decreased villi and
  crypts
• decreased enzyme secretion
• impaired motility
• tendency for bacterial overgrowth
• maldigestion and malabsorption

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Starvation

• Changes in Organ Function
• Liver loss of mass
• decreased protein synthesis
• periportal fat accumulation (fatty liver)
• hepatic insufficiency
• Skeletal muscle
• catabolized for GNG - decreased mass
• utilization of ketones slower contractions
• diminished function intercostal muscles -
  decreased respiratory function

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Starvation

• Changes in Organ Function
• Cardiovascular system
• decreased cardiac output
• bradycardia, hypotension
• dilatation, degeneration, fibrosis
• central circulation takes precedence, leads to
  postural hypotension
• Respiratory system
• decreased cilia, reduced bacterial clearance
• decreased deep breathing

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Starvation

• Changes in Organ Function
• Kidney
• decreased perfusion, decreased GFR
• increased GNG
• increased NH4 excretion
• Immune function
• decreased T-lymphocyte count
• decreased cytokine activity
• anergy
• increased infection rate (pneumonia)

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Starvation

• Changes in Organ Function
• Nervous system
• decrease in nerve myelination
• decrease brain growth

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Successful Adaptation

• Goals
• 1. Maintain glucose homeostasis and conserve
  glucose pool.
• 2. Preserve structural and functional lipids and
  proteins
• 3. Preserve the organism
• Preferential visceral uptake of AA released by
  peripheral tissue

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Failed adaptation

• Metabolic disease hyperthyroidism/thyroid storm,
  insulinoma
• Micronutrient deficiency - mineral deficiency
  interferes with protein sparing
• Food restriction too severe
• Metabolic stressors such as infection, surgery
  lead to hypermetabolic state

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Hypermetabolic State and Cachexia

• Wounds, surgical stress, cancer, inflammatory
  conditions and infection
• Increased production of cortisol, interleukins,
  TNF
• hypercatabolic state with increased RMR
  increased energy requirements
• Insulin resistance, hyperglycemia - no starvation
  adaptation, poor utilization of stubstrate
• Protein breakdown continues unabated
• In 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

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PCM Clues to Cause From Body Composition Analysis

• Energy depletion (reduced fat stores) out of
  proportion to LBM loss Starvation Marasmus
• Predominant protein depletion (reduced
  LBM) Cachexia Kwashiorkor
• Combined (Marasmic Kwashiorkor) Most common PCM
  seen in hospitalized patients

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PCM Marasmus in Hospitalized Patients

• Severe Energy Depletion Temporal wasting
  observed with ageing and reduced intake

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PCM Marasmus in Hospitalized Patients

• Severe Energy Depletion Loss of Skinfold
  Thickness

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Nutrition AssessmentHospital or Clinic Screening

• Identifying and treating malnutrition
• Preventing Hospital-Acquired Malnutrition
• Assessing nutrition risk on admission
  JCAHO-mandated database
• more to come...