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:– 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 -->-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:

• 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:– 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

4 8 12 16 20 24 28 2 8 16 24 32 40

HOURS DAYS

III III IV V

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%– 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

• 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• 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”

• Wounds, surgical stress, cancer, inflammatory conditions Wounds, surgical stress, cancer, inflammatory conditions and infectionand 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 unabatedProtein 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

Hypermetabolic State and CachexiaHypermetabolic State and Cachexia

PCM: Clues to Cause From PCM: Clues to Cause From Body Composition AnalysisBody Composition Analysis

• Energy depletion (reduced fat stores) out of proportion to LBM loss:Starvation = MarasmusStarvation = Marasmus

• Predominant protein depletion (reduced LBM): Cachexia = KwashiorkorCachexia = Kwashiorkor

• Combined (Marasmic Kwashiorkor): Most common PCM seen in hospitalized patients

PCM – Marasmus in PCM – Marasmus in Hospitalized PatientsHospitalized Patients

Severe Energy Depletion: Temporal wasting Severe Energy Depletion: Temporal wasting observed with ageing and reduced intakeobserved with ageing and reduced intake

TemporalTemporalwastingwasting

PCM – Marasmus in PCM – Marasmus in Hospitalized PatientsHospitalized Patients

Severe Energy Depletion: Loss of Severe Energy Depletion: Loss of Skinfold ThicknessSkinfold Thickness

Nutrition AssessmentNutrition AssessmentHospital or Clinic ScreeningHospital or Clinic Screening

• Identifying and treating malnutrition • Preventing Hospital-Acquired Malnutrition

• Assessing nutrition risk on admission: JCAHO-mandated database

• more to come...