Classification of PEM in young children

Condition Body weight as Oedema Deficit in weight-for-

percentage of length
international standard
Kwashiorko 80 – 60 + +
r
Marasmic < 60 + ++
kwashiorko
r
Marasmus < 60 0 ++
Nutritional < 60 0 Minimal
stunting
Underweig 80 – 60 0 +
ht child
Essentials of Human Nutrition, 2010
 Various classifications

Gomez classification

Waterlow’s classification

Wellcome classification

Indian Academy of Pediatrics (IAP)

classification

Standard deviation classification

 Clinical Forms of PEM

PEM occurs in three clinically distinguishable forms:

1. Kwashiorkor 2. 3. Marasmic kwashiorkor

Marasmus
 Kwashiorkor

Kwashiorkor is an African word, taken from the Ga language of

Ghana, meaning a “disease of the displaced child”, who is
deprived of adequate nutrition.

It is the form of malnutrition where there is inadequate

protein intake.

The term ‘kwashiorkor’ was first introduced by Cicely Williams

in 1933.

It occurs between the ages of 1 – 3 years, when they are

completely weaned (taken off the breast).
 Clinical signs of Kwashiorkor

Oedema
Underweight
Epathy and irritability
Moon face
Hair changes
Skin changes
Micronutrient deficiencies
Water and electrolyte imbalance
Changes in Kwashiorkor
 Marasmus

• The term marasmus comes from Greek word

‘marasmos’ meaning ‘to consume, exhaust’.
• It is a form of severe PEM characterized by
energy deficiency.
• It can occur at any age but most severe cases
are seen in children below 2 years of age.
• It can be described as a bonny cage having
nothing but “skin and bones”.
 Clinical signs of Marasmus

Severe growth retardation

Extreme emaciation

Loose and hanging skin folds

Old man’s or monkey face

Extreme muscle wasting

Changes in Marasmus
 Metabolic adaptation to energy deficiency in marasmus
Inadequate food
intake
Normal plasma
insulin

Reduced plasma
Adipose tissue insulin Skeletal muscle
lipids proteins

G Cortisol
H
Free fatty Free amino
acids 2 acids
NH
a
ß- De Hepatic
ox Energy m protein
ida
tio metabolism g synthesis
n Gn
Plasma
Energy proteins
Foods – Nutrition & Health, 2003
Endocrine adaptive functions in PEM

Modern Nutrition in Health and Disease, 2006

 Biochemical Findings In Kwashiorkor And Marasmus
Kwashiorkor Marasmus
Plasma albumin Very low Usually normal
Plasma amino acids Reduced branched chain More normal
and tyrosine
Serum amylase Very low Norma/ low normal
Plasma (total) cholesterol Very low Normal/low normal
Plasma free fatty acids Increased Increased
Plasma growth hormone Raised Not as high
Fasting blood glucose Low to normal Low
T lymphocytes Low Low
Plasma retinol Low Low
Plasma transferrin Very low Low to normal
Plasma urea Low Not as low
Plasma zinc Low Not as low

Essentials of human nutrition, ed. by Mann and Truswell, 2010 pp. 263
 Difference between Marasmus and Kwashiorkor
Features Marasmus Kwashiorkor
Essential features
Oedema None Lower legs, sometimes face or
generalized
Wasting Gross loss of Less obvious
subcutaneous fat, “all
skin and bones”
Muscle wasting Severe Sometimes
Growth retardation Severe Less than Marasmus
Mental changes Usually none Usually present
Variable features
Appetite Usually good Usually poor
Diarrhea Often Often
Skin changes Usually none Often
Hair changes Texture modified but no Often sparse and
dyspigmentation dyspigmentation
Moon face None Often
Hepatic enlargement None Frequent
 Marasmic Kwashiorkor

• In this, malnourished children exhibit the features

of marasmus as well as kwashiorkor.
• Transition from one form of malnutrition to the
other is not uncommon.
• Such a child will have extreme wasting of different
degrees (representing marasmus) and also oedema
(a sign of kwashiorkor).
Clinical signs of Marasmic kwashiorkor

Extreme muscle
wasting – “skin and
bones”
Old man’s or
monkey’s face

Absolute weakness

Oedema
 Treatment of Protein Energy Malnutrition

Treatment strategy
Resolving life- Restoring nutritional
status without
threatening disrupting
conditions homeostasis

• Fluid & electrolyte • Therapeutic dietary

balance regimens Ensuring
• Infections
• Structural nutritional
increments rehabilitation
• Severe anemia • Sequential
• Hypothermia & administrations of
hypoglycemia two formulations
with different
• Severe vitamin A
nutrient
deficiency concentrations
 EFFECT OF PROTEIN ENERGY
MALNUTRITION ON HUMAN BODY
 PEM and
Skin change
s

PEM and PEM and

Other Immunity

EFFECTS

PEM and
PEM and
Biochemical
Cognition
changes
 Protein Energy
Malnutrition and
Skin Changes
Effect of protein malnutrition on the skin epidermis of hairless
mice

A low
Dityrosine was immuno
protein
stained in the cytoplasm of
diet
epidermal cells in the
given to
low protein diet group.
mice.

• thinning of the skin epidermis

• a decrease of cell proliferative activity in epidermal cells
• a decrease of stratum corneum hydration
• Plasma advanced oxidation protein product (AOPP) levels were significantly
more increased

Results: protein malnutrition adversely affects the structure and water

barrier and reservoir functions of the skin epidermis, and these pathological
changes are associated with the expressions of protein oxidation markers,
dityrosine and AOPP.
Sugiyama et al, 2011
 Experimental models of malnutrition and its effect on skin
trophism.
• 30 rats – controlled diet
Subjects • 30 rats – established diet
• body mass index, clinical signs and serum albumin was measured.
• histology was performed to analyze the thickness of the dermis and
epidermis
Method
• Collagen was analyzed

• Body mass index was lower in malnourished group

• No difference in serum albumin
• Thinner dermis of the malnourished animals
Results • Percentage of collagen was lower

• Skin thickness measurements were lower in the

malnourished animals, showing the negative effect
Conclusion
of malnutrition on skin trophism.
Leite et al, 2011
 Protein Energy
Malnutrition and
Immunity
 Study of lymphocyte subpopulations in bone marrow in a model of
PEM

Swiss mice were subjected to PEM using a low-protein diet containing

4% protein until the experimental group had lost about 20% of their
original body weight

Blood and bone marrow cells were collected and the hemogram, the
myelogram, bone marrow lymphoid markers using flow cytometry, and
the cell cycle in CD5+ bone marrow was evaluated.

Conclusion: bone marrow hypoplasia, maturation interruption,

prominent lymphopenia with depletion in the lymphoid lineage, and
changes in cellular development was observed. These changes are
some of the primary causes of lymphopenia in cases of PEM and partly
explain the increase in susceptibility to infections found in malnourished
individuals.

Fock et al, 2010

 Prostaglandin E2 is raised in kwashiorkor

Method
Plasma PGE2 Results Conclusion
and plasma proteins Higher PGE2 levels
were measured in Plasma PGE2 was
in children
children admitted higher in children
with with kwashiorkor
with kwashiorkor  (reason for the
oedematous kwashior
kor, and compared than in control depression of
with PGE2 in children children. immune function)
with cerebral palsy.

Iputo et al, 2002

 EFFECTS OF PEM ON THE IMMUNE SYSTEM

PEM is believed to lead to an increased susceptibility to

infection, or cause impaired immunity. Infection, occurring with
malnutrition, is a major cause of morbidity in all age groups and
is responsible for two-thirds of all death under 5 yr of age in
developing countries. Many cells of the immune system are
known to depend for their function on metabolic pathways that
employ various nutrients as critical factors. The most consistent
changes in immune competence in PEM are in cell-mediated
immunity, the bactericidal function of neutrophils, the
complement system, the secretory immunoglobin A, and
antibody response.
Masrizal, 2003
Effects of PEM on NF-kappaB signalling in murine peritoneal
macrophages.

Method Results Conclusion

Experimenta Anemia, leucopenia and PEM

l - 2-mth old severe reduction in changes
peritoneal cavity
mice with a cellularity was NF-kB
low- observed. TNF-alpha signalling
protein diet mRNA pathway
(2% protein) and protein levels of in
macrophages
Control – stimulated with macropha
(12% protein (lipopolysaccharide) LPS ges to LPS
) were significantly lower. stimulus.
NF-kappaB activation
after LPS stimulation
was also decreased.
Fock et al, 2010
 Protein Energy
Malnutrition and
Cognition
 Early Postnatal Protein-Calorie Malnutrition and Cognition: A
Review of Human and Animal Studies

Reviewed 18 human and 37 animal studies relating malnutrition to cognitive

development, focusing in correlational and interventional data, and to provide a
discussion of possible mechanisms by which malnutrition affects cognition.

Human studies found that severe postnatal protein-calorie malnutrition negatively

influences cognitive development. These co relational studies have demonstrated
significant associations between malnutrition and deficits in analytic and
reasoning skills, language i.e. verbal fluency, vocabulary, verbal comprehension;
visuospatial working memory; visuospatial functions, attention and learning;
intellectual performance (including IQ) and educational achievement.

In prenatal and postnatal malnourished rats leads to increased motivation for food or water
in response to emotional reactivity and sensitivity to painful stimuli, reduction in cognitive
flexibility and learning and memory impairments.

Summary: Malnutrition imposed in early life has significant and lasting implications for the
development of cognition both in humans and animals.

Laus et al, 2011

The effects of PEM on the central nervous system in children

Computerised tomography brain

scans and MRI in children
suffering from malnutrition show
images that are compatible with PEM produces notable morphological
cerebral atrophy. The lack of changes in the brains of children in
environmental stimulation the developing world. These changes
associated with malnutrition damage the intellectual potential of
worsens the damage to the those who survive and limit their
central nervous system. All the capacity to become part of the
alterations that are observed in competitive world.
such cases give rise to important
compromise of the child's higher
brain functions, which may well
lead to permanent
neuropsychological damage. Cornelio-Nieto, 2007
 Cognitive development in children with chronic PEM

Method:
Conclusion:
NIMHANS
Chronic PEM (stunting)
neuropsychological
affects the ongoing
battery for children
development of higher
Subjects: sensitive to the effects of
cognitive processes during
20 brain dysfunction and
childhood years. Stunting
malnourished age related improvement
could result in slowing in
children was employed. The
the age related
20 nourished battery consisted of tests
improvement in certain and
children of motor speed,
not all higher order
attention, visuospatial
cognitive processes and
ability, executive
may also result in long
functions,
lasting cognitive
comprehension and
impairments.
learning and memory

Kar et al, 2008

 The effects of perinatal protein malnutrition on spatial
learning and memory behaviour and brain-derived
neurotrophic factor concentration in the brain tissue in
young rats
9 pregnant rats • Rat pups fed with low protein diet had lower body weight
Group 1 = control and slightly lighter brain compared to the control pups.
diet (20% protein) • Total protein levels in hippocampus and cerebral cortex
Group 2 = 6% protein were significantly lower in malnourished pups than the
from gestation day 8 controls.
till 4 weeks after • The concentration of BDNF in the hippocampus was also
birth significantly lower in rat pups suffered protein malnutrition
Group 3 = 6% protein from early pregnancy than in the controls.
from gestation day • Morris Water Maze (MWM) tests showed that perinatal
15 till 4 weeks after protein deprivation, particularly from early pregnancy,
birth significantly impaired learning and memory ability.
Perinatal protein malnutrition had adverse influence on spatial navigation and
brain BDNF levels in rats. The decreased hippocampal BDNF concentration might
partially contribute to the poor learning memory performance in the protein
deprived rats.
Wang and Xu, 2007
 Protein Energy
Malnutrition and
Biochemical Changes
 The effects of early protein malnutrition and environmental
stimulation on behavioral and biochemical parameters in rats

W – well-nourished rats (16% protein diets)

M – malnourished rats (6% protein diets) and were divided into stimulated or
non-stimulated groups.

Malnutrition increased corticosterone levels and decreased plasma protein and

anxiety. The exploratory behavior was analyzed using the elevated plus-maze
(EPM) test. Non-stimulated rats tested in the EPM had increased corticosterone
levels and decreased frontal cortex, striatum and hippocampus protein and
polyamines contents.
both malnutrition and EPM testing are distressing situations, as indicated by
increased corticosterone levels.

Sampaio et al, 2008

 Serum vitamin A levels in children with PEM

Subjects: Methodology:
197 children = The serum vitamin
98 A level, serum
malnourished + albumin and body
97 healthy mass index was
estimated.
Results:
Serum Vitamin A, serum albumin
and BMI were significantly Conclusion:
decreased. When comparison was vitamin A is
done between malnourished significantly lowered
children suffering from kwashiorkor in malnourished
and the marasmic children, children irrespective
significant decrease was observed in of the class of PEM.
serum albumin of children suffering
from kwashiorkor but not in serum
Ikekpeazu et al, 2010
vitamin A level and BMI.
Impaired glucose absorption in children with severe
malnutrition.

Conclusion:
Severe
Results: malnutrition is
lowest glucose associated with an
absorption were impaired glucose
Intervention: found absorption and
Primed (13 in kwashiorkor gro decreased glucose
mg/kg), constant up and marasmic absorption
infusion (0.15 children with correlates with
mg/kg/min) of hypoalbuminemia. oxidative stress in
Subjects:
Kwashiorkor (n = glucose for 4.5
these children.
6) hours
Marasmus (n =
9) Bandsma et al, 2011
Control (n = 3)
 Serum zinc and copper level in children with PEM

Subjects
n = 68
Group I (Control; n=20)
Group II-(children with PEM; n=48): 3
subgroups
Group IIA: Marasmus (n=19)
Group IIB: Kwashiorkor (n=14)
Group IIC: Marasmic Kwashiorkor (n=15)
Method
Serum zinc and copper levels
were determined by Atomic
Absorption
Spectrophotometric method.

Results
Serum zinc and serum copper in Marasmus, Kwashiorkor and
Marasmic Kwashiorkor were all significantly lower than in control
group.
Conclusion
Serum zinc and copper level significantly decrease in children with
PEM.
Gautam et al, 2008
 Hypo-phosphataemia in children under five years
with kwashiorkor and marasmic kwashiorkor.

Conclusion
Subjects Hypo-
165 children = phosphataemia is
107 kwashiorkor, frequent among
58 children
marasmic kwashio Results with kwashiorkor an
rkor. There was a positive d
association between marasmic kwashiork
severity of serum or.
phosphate level and
mortality. There were
no deaths among
children with normal
serum phosphate
levels.
Kimutai et al, 2009
Kwashiorkor and marasmus are both associated with impaired
glucose clearance related to pancreatic β-cell dysfunction

A primed Glucose Glucose

Kwashiorkor

Intervention
Subjects

Results

Conclusion
clearance rates clearance rates
=6 (13 mg/kg), are affected in
constant correlated with marasmus as well
Marasmic = infusion plasma as kwashiorkor,
8 (0.15 mg/kg/ albumin which correlate
min) of concentrations with plasma
Healthy = 3 glucose for 4 h . Insulin albumin
concentrations.
with serial responses
The disturbed
blood were strongly glucose clearance
impaired in is related to an
sampling.
both impairment in
kwashiorkor insulin
and marasmus. availability.

Spoelstra et al, 2012

 Antioxidant Status and Nitric Oxide in the Malnutrition
Syndrome Kwashiorkor

In comparison with local healthy controls, the plasma total

antioxidant status was reduced to less than 50% in the kwashiorkor
patients. Similarly, the major plasma antioxidant albumin and
erythrocyte glutathione were decreased, whereas the levels of
bilirubin and uric acid were not significantly altered. Nitrite and
nitrate were found to be increased by a factor of 2 in kwashiorkor.

Oxidative stress play a role in the pathophysiology of edematous

malnutrition.

Fechner et al, 2001