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

II

12

III

16

20

IV

24

HOURS

28

16

24

32

DAYS

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

40

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

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:

JCAHO-mandated database
more to come...