Download Protein Calorie Malnutrition

Protein Calorie Malnutrition
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
Malnutrition in Hospitalized Pts
• Consequences for hospitalized pts:
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poor wound healing
higher rate of infections
greater length of stay
greater costs
Increased morbidity and mortality
Definitions
• Fast: exclusion of all food energy
• Starvation: prolonged inadequate intake of
protein and/or energy
• Cachexia: wasting induced by metabolic
stress
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
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
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
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
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
Gluconeogenesis
• Cori cycle in Liver
– glucose --> converted to lactate/pyruvate in
skeletal muscle (anaerobic)-->travels back to
liver for conversion to glucose
Gluconeogenesis
• Glucose-Alanine Cycle: Liver
– AA deaminated in muscle
– C-skeleton used for energy -->pyruvate and
NH2 --> alanine
– alanine returns to liver for deamination
– NH2 -->urea for excretion
– pyruvate --> glucose via GNG
Gluconeogenesis
• Glutamine cycle in Kidney
– Muscle 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 days
• GNG ongoing, sources of substrate:
– endogenous glycerol
– alanine and glutamine from muscle
– lactate and pyruvate
• Ketosis
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
Fast longer than 2-3 days
• Significant protein loss during first 7-10
days
– Body protein losses:
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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 <1/3 of initial (not yet
understood)
Long Term Starvation (>7-10d)
• 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
Long Term Starvation (>7-10d)
• Decreased glucose availability
– Brain:
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fed state: uses 75% (140g/day), completely oxidized
>3 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
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 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
Minnesota study (1944-1946)
• Decrease in metabolic rate by 40%
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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”
Starvation
• Functional alterations
– hormonal changes
• decreased thyroid fx --> decreased BMR
• decreased gonadotropins
• decreased somatomedins --> decreased
muscle/cartilage synthesis, decreased growth
– decreased metabolic rate and caloric need
– decreased body temp
– decreased activity, increased sleep
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
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
Starvation
• Changes in Organ Function
– Cardiovascular system
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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
Starvation
• Changes in Organ Function
– Kidney
• decreased perfusion, decreased GFR
• increased GNG
• increased NH4 excretion
– Immune function
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decreased T-lymphocyte count
decreased cytokine activity
anergy
increased infection rate (pneumonia)
Starvation
• Changes in Organ Function
– Nervous system:
• decrease in nerve myelination
• decrease brain growth
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
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”
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
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
PCM – Marasmus in Hospitalized
Patients
Severe Energy Depletion: Temporal wasting
observed with ageing and reduced intake
Temporal
wasting
PCM – Marasmus in
Hospitalized Patients
Severe Energy Depletion: Loss of Skinfold
Thickness
Nutrition Assessment
Hospital or Clinic Screening
• Identifying and treating malnutrition
• Preventing Hospital-Acquired Malnutrition
• Assessing nutrition risk on admission: JCAHOmandated database
• more to come...