Nutritional disorders 47

NUTRITIONAL DISORDERS
Malnutrition is defined as a pathological state resulting from a relative or absolute deficiency, or
excess of one or more essential nutrients. It is one of the leading causes of morbidity and mortality
in childhood especially in tropics and subtropics. It is due to lack of protein and calories in varying
proportions.
Forms of malnutrition
a- Under-nutrition: results from the consumption of an inadequate quantity of food over an
extended period of time. It is due to either deficiency of all nutrients or of one or more
components.
b- Over-nutrition: denotes a pathological state resulting from excess intake of all or of one or
more of nutrients.
Assessment of nutritional status
1- Feeding history: age of the patient, duration of exclusive breast feeding, time of introduction,
type, amount and frequency of food given to children particularly in weaning period, number of
attacks of diarrhea and history of repeated starvation during attacks of diarrhea.
2- Clinical examination for signs of malnutrition.
3- Anthropometric measurements: are usually practical, low cost and do not need much skill or time.
These include height, weight, skin fold thickness, mid upper arm circumference………etc
International standards of normal child growth under optimum conditions from birth to 5 yr have
been established.

The standards allow normalization of anthropometric measures in terms of z scores

z scores (standards deviation scores) is a measure of the dispersion of data (j.e the spread of
data away from normal reference population)

Standard deviations can also be called z scores

Normal standard deviation values range from -1 to +1

The terminology of -2 z scores means -2 standard deviations below the average.

The terminology of- 3 z scores means -3 standard deviations below the average.
Calculation of exact z scores by using this formula

z scores = Measured value height (weight) –Average value in the reference population
standard deviations of the reference population
a- Height-for-age (or length-for-age for children<2yr ) is a measure of linear growth ,a deficit
represents chronic malnutrition
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Nutritional disorders
b- Weight for age: is the most commonly used index for assessing the nutritional status by
monthly weighing the infant .Weight deficit appears early in the course of malnutrition, it does not
differentiate between wasting and stunting.
c- Weight for height: ,or wasting ,usually indicates acute malnutrition .
d- Mid-arm circumference: (midway between the acromion and olecranon). It measures the
subcutaneous fat and muscles. It is a simple and quick screening method for malnutrition that
demonstrates the degree of muscle wasting and is not affected by edema; normally it is 13.5 cm
from age 6-59 mo. Levels between 11.5 and 12.5 cm indicate moderate malnutrition, while levels
below 11.5 cm indicate severe malnutrition.
e- Body mass index:is calculated by dividing weight in kg by the square of height in meters.
BMI-for-age can be used from birth to 20 yr and is a screening tool for wasting (<-2SD).
f- Skin fold thickness: the skin and subcutaneous fat are pinched by a special caliber over the
deltoid or sub scapular region, this thickness is measured and it reflects amount of the
subcutaneous fat.

Table 6-1 Assessment of nutritional status

classification Index Grading
Gomez 90-75% of expected weight Crade 1(mild)
(underweight) 75-60% of expected weight Crade 2(moderate)
median weight-for – age <60% of expected weight Crade 3(servere)
WHO (wasting ) <-2 to>-3 SD Moderate
Weight-for-height <-3 Severe
WHO (wasting) 115-125 mm Moderate
mid-upper arm circumference <115mm Severe
(for age group 6-59 mo)

Classification of malnutrition
Malnutrition comprises a variety of very closely interrelated clinical syndromes ranging from mild
and moderate forms to severe syndromes of marasmus (severe wasting),
kwashiorkor(characterized by edema) ,marasmic- kwashiorkor (severe wasting and edema).

Mild malnutrition
This form of malnutrition manifests by inadequate physical growth. It is the commonest form of
malnutrition in the post-weaning period from about 6 months- 2 years. The main features are:
1- Growth failure: children are small for their age as manifested by:
 Nutritional disorders 49

a- Slowing or cessation of weight gain or loss of weight.

b- Slow or cessation in linear growth (length), with normal or diminished weight/height ratio.
c- Decrease in mid-arm circumference.
d- Normal or diminished skin fold thickness.
The best way to measure a child’s nutritional status is to weigh him regularly every one or two
months and plot these weights on charts that show standard growth curves for comparison.
2- High rate of infection: e.g. diarrhea, pneumonia and parasitic infestation due to decreased
immunity.
3- Decreased activity: the child is less active than normal children of the same age.
4- Retardation of motor development: malnourished children may walk later than normal children
of similar age.
5- Anemia: there is a moderate degree of nutritional anemia in children with malnutrition.

SEVERE ACUTE MALNUTRITION

Definition: severe acute malnutrition is defined as severe wasting and/or bilateral edema.
Severe wasting is extreme thinness diagnosed by weight for length or height below -3 SD of the
WHO growth standards. In children aged 6-59 months, mid arm circumference <115 mm also
denotes extreme thinness.
Pathophysiology
The liver
 It makes glucose less available, making the child more prone to hypoglycemia .
 It synthesizes less albumin, transferrin, and other transport proteins.
 It is less able to cope with excess dietary protein and less able to excrete toxins.
The heart
 It is smaller and weaker .
 Heart failure (see complications)

The kidneys
 They are less able to excrete excess fluid and sodium .
The gut
 It produces less gastric acid and enzymes.
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Nutritional disorders
 Motility is reduced, and bacteria may colonize the stomach and small intestine, damaging
the mucosa.
 The level of disaccharidases in brush border is low due to atrophy of gut mucosa. There is
lactose intolerance, due to lactase deficiency.
 Digestion and absorption are impaired.
Heat production: it is less, making the child more vulnerable to hypothermia.
Sodium
 Normally sodium and potassium pump preserves potassium intracellular and sodium
extracellular. Sodium builds up inside cells due to damage of cell membranes and reduced
activity of the sodium /potassium pump, leading to excess intracellular sodium, fluid
retention with edema and hyponatremia.
Potassium
Leaks out of cells and is excreted in urine lead to hypokalemia.
Micronutrients deficiency
- Vitamin A deficiency
- Iron deficiency anemia
- Zinc deficiency increases risk of mortality from diarrhea, pneumonia and has adverse
effects on linear growth
Immune function
 It is impaired, especially cell-mediated immunity

Kwashiorkor

Definition
The term kwashiorkor is taken from language of Ghana and refers to the deposed child. It
describes the affection of a child on arrival of a new baby who deposes or deprives him from the
breast, so it usually becomes evident after weaning. It results mainly from lack of protein in the
diet.

Etiology
Dietetic error: feeding of child with an imbalanced diet very low in protein (mainly high
biological value proteins) but contains normal or high amount of carbohydrates, such as cereal
grains, starchy products or fruits.
 Nutritional disorders 51

Infections: diarrhea, respiratory infections and parasitic infestations play an important role in
precipitating the onset of kwashiorkor in already malnourished children.
Clinical picture
Age incidence: ranges from 6 months-3 years.
General appearance: a child with kwashiorkor may have a fat appearance with a doll like facies
(sugar baby) where the diet provides an adequate energy source and there is preservation of
subcutaneous fat. The illness is insidious because subcutaneous fat is frequently preserved
together with the gradual development of edema that masks the wasting of the underlying tissues.
Growth failure: it is a constant and early feature of kwashiorkor. There is decreased body
weight for age despite the presence of edema and preserved subcutaneous fat. The disturbances
of growth vary in degree depending on duration and severity of malnutrition.
Muscle wasting: it is a constant sign of kwashiorkor, muscles are wasted and their tone is
diminished. It is best determined by measuring the mid-arm circumference together with skin fold
thickness. In kwashiorkor, mid-arm circumference is below the lower limit of normal but skin fold
thickness is within normal range due to preservation of subcutaneous fat.
Pitting edema: it is a constant manifestation of kwashiorkor. Edema is pitting and starts in lower
limbs or dependant parts. It ranges from mild to gross forms affecting whole body. The main
causes are low serum albumin, and altered capillary permeability due to protein deficiency.
Ascites is very rare, if it is present, renal affection,
tuberculosis, low-grade peritonitis or liver cirrhosis should be excluded.
Mental changes: apathy is a constant, early and pathognomonic sign of kwashiorkor. Apathy
means decreased emotional reactivity. Most children are disinterested in their environment and
have an expression of misery and prefer darkness. They make no effort to secure interesting toys.
In some hospitals, the return of smiles signals the time of discharge. Mental changes have been
explained by hypoglycemia, imbalance in the ratio of essential to non-essential amino acids,
deficiency of some amino acids (e.g. phenylalanine), cerebral potassium deficiency,
hypomagnesaemia, zinc deficiency and/ or cerebral edema.
Skin changes: the skin changes consist of erythema, hyperpigmentation, desquamation,
depigmentation and ulceration. The pigmented areas become confluent with fissures in between.
The epidermis peels off in large scales, this gives rise to flaky (cracky) paint dermatosis.
Underneath these flacks the skin is atrophic and depigmented. Flaky paint dermatosis is a
pathognomonic sign of kwashiorkor. The distribution of the dermatosis is typically on the
buttocks, perineum and upper thighs (the area of soiling, wet diapers, continuous pressure or
irritation). The lesion may be found anywhere on the body especially extensor surfaces of the
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Nutritional disorders
body. It is probably due to deficiency of essential fatty acids, essential amino acids especially
tyrosine, nicotinic acid, vitamin A and zinc.
Hair changes: hypochromotrichia means reduced hair pigmentation; black hair becomes brown
or reddish yellow and sometimes even gray. The nutritional insult that causes dyspigmentation had
occurred l-3 months before the color changes could be seen in the scalp hair. Hypochromotrichia
is related to the lack of tyrosine needed for normal production of melanin and deficiency of copper
that is responsible for pigmentation of hair and skin. The hair becomes dry straight, sparse and can
be pulled out easily and without pain. Flag sign (segmental hypochromotrichia) means
appearance of alternating bands of depigmented and normal black hair. The pigmented areas
represent alternating periods of better nutrition. The dyspigmented areas represent periods of
malnutrition. Flag sign is pathognomonic for kwashiorkor.
Gastrointestinal disturbances
1- Anorexia: is a constant and early feature that may be severe and necessitates tube feeding.
2- Diarrhea: is almost always present in children with kwashiorkor and it is due to infection (by
Salmonella, Shigella, E-coli or Candida albicans) or due to disaccharidases deficiency (lactase,
sucrase and maltase). The stools are frequently of low pH and may contain excess unabsorbed
lactic acid.
3- Abdominal distension: due to hypokalemia, malabsoption of disaccharides which leads to
fermentation and distension, parasitic infestation (e.g. giardiasis) and toxic ileus.
4- Hepatomegaly: liver is enlarged and soft due to fatty infiltration.
Anemia: due to lack of iron, folic acid, vitamin B6 and vitamin B12. Bone marrow depression
secondary to protein deficiency, infection and parasitic infestation may occur. Microcytic
hypochromic, megaloblastic and normocytic normochromic anemias may be present.
Signs of vitamin deficiency: cracking of the lips (cheilosis) and angular stomatitis are common
due to vitamin B complex deficiency. Vitamin A absorption and probably transport are impaired.
Vitamin A deficiency leads to severe ocular lesions (xerophthalmia, Bitot spots and
keratomalacia).
Cardiovascular system: patients suffering severe malnutrition have cold, pale or cyanotic
extremities due to circulatory insufficiency.
Associated infection: pneumonia, infective diarrhea and urinary tract infection are common, due
to decreased immunity.
Table 6-2 Features of kwashiorkor
Constant features of kwashiorkor Pathognomonic signs Common signs
Present in every case of Kwashiorkor When present, they are diagnostic They are present in most cases
1- Apathy or misery. 1- Apathy. 1- Signs of vitamin deficiency.
 Nutritional disorders 53

2- Edema. 2- Cracky paint dermatosis 2- Anemia.

3- Anorexia. 3- Flag sign. 3- Skin changes.
4- Growth failure 4- Hair changes.
- Decreased body weight. 5- Infections and diarrhea
- Muscle wasting.
5- Fatty infiltration of liver.
6- Hypoproteinemia.

Differential diagnosis of kwashiorkor

I- Edema of kwashiorkor: should be differentiated from other causes of generalized edema
(renal, cardiac and hepatic edema), see table 6-3.
II- Differential diagnosis of dermatitis (skin lesions)
a- Napkin dermatitis: affects skin of external genitalia, inner sides of the thighs and the
buttocks.
b- Monilial infection: red, moist lesion with well defined edge.
c- Acrodermatitis enteropathica: it is due to deficiency of zinc. It manifests by chronic diarrhea,
skin lesions, stomatitis, growth retardation and intercurrent infection.
Laboratory features of kwashiorkor
1- Plasma proteins especially the albumin are decreased (normally total proteins are 6-8 gm/dL,
albumin is 4-5 gm/dL). Alpha and beta globulins are diminished, but gamma globulin is increased
especially with infection.
2- The essential amino acids are low especially leucine, isoleucine, valine and tyrosine. The non-
essential amino acids are usually elevated; there is a high ratio of non-essential/essential amino
acids.
3- Plasma beta lipoproteins, cholesterol, triglycerides and fat-soluble vitamins are decreased.
4- Serum levels of potassium, sodium, magnesium and copper are decreased.
5- Serum levels of amylase, lipase and alkaline phosphatase are also reduced.

Table 6-3 Differences between kwashiorkor, renal, cardiac, and hepatic edema
Item Kwashiorkor Renal Cardiac Hepatic
(nephritis–nephrosis) (heart failure) (liver cirrhosis)
History
- Age 6 months - 3 years 2-6 yr, in nephrosis, Any age Any age
5-12 yr, in nephritis
- Anorexia Severe & constant May be present May be present May be present

- Initial site of edema Dorsum of the feet Around the eyes Lower limbs Abdomen (ascites)

Examination
- Weight Decreased Normal or increased Normal or decreased Normal or decreased
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Nutritional disorders
- Blood pressure Normal High especially in Variable Normal
nephritis

- Jaundice Absent Absent Uncommon Commonly present

- Skin changes Cracky paint der- Pallor may be present Cyanosis may be Palmar erythema,
matosis may occur present spider nevi

- Flag sign of hairs May occur Absent Absent Absent

- Signs of heart failure Absent Uncommon Present Absent

- Liver Enlarged, soft Normal Enlarged, soft, may Firm, sharp edged,
be tender enlarged or shrunken

- Ascites Very rare May be present Late Early

Laboratory findings
- Proteinuria Mild Heavy in nephrosis Transient Absent
moderate in nephritis.

- Hematuria Absent More in nephritis With infective endo- May be present with
carditis bleeding tendency
- Hypoproteinemia present Present Absent Present

Marasmus
It is a chronic state of general under-nutrition with progressive loss of weight, gross wasting of
muscles and subcutaneous tissue.
Pathogenesis
With severe restriction of food intake, first the infant stops growing and begins to utilize his own
subcutaneous fat then his muscles leading to the gross appearance of skin over bone. The main
pathological changes are the marked loss of stored fat and muscle wasting. The basal metabolic
rate (BMR) and oxygen consumption fall due to decrease in the active form of thyroid hormone at
the cellular level. Rates of cellular division and protein synthesis are also decreased.
Etiology
Dietetic or primary causes (nutritional marasmus)
Nutritional marasmus is most commonly observed in tropics and is the result of starvation. The
diet may be adequate in quality but very insufficient in amount to satisfy the minimum daily
requirements of the rapidly growing child.
1- Infants fed exclusively on mother’s milk that is inadequate (breast fed starvation).
2- Cessation of breast-feeding due to failure of lactation or separation from the mother.
3- Artificially fed infant, given an over-diluted cow’s milk or infant formula.
 Nutritional disorders 55

4- Early weaning, giving insufficient amounts of foods.

5- Erroneous concept of dietary restriction and keeping the infant on oral fluids for long period
for treatment of diarrhea.
6- Food allergy: is an infrequent cause of malnutrition.
Non-dietetic causes of marasmus
1- Secondary marasmus may be due to poor sanitary conditions of the environment in
developing countries leading to repeated attacks of diarrhea or chronic gastroenteritis.
. Chronic or recurrent attacks of diarrhea contribute to deterioration of nutritional state that
leads to reduction of host resistance, and worsening the outcome of infection, establishing a
vicious diarrhea-malnutrition cycle, see chapter 9.
Impaired immunity

Malnutrition Intestinal enzyme deficiency Diarrhea

Hypercatabolism

Malabsorption

2- Age of the child: rapidly growing young age groups are more susceptible to severe
malnutrition.- Premature and low birth weight infants are susceptible to marasmus because they
have difficulties in suckling, and low digestive and absorptive power.
3- Local disease or malformation of the mouth (e.g. cleft palate) that interferes with adequate
feeding.
4- Persistent vomiting as in cases of pylorospasm and congenital pyloric stenosis.
5- Chronic debilitating diseases such as TB., empyema, chronic meningitis, chronic
pyelonephritis, liver diseases, heart diseases or malignant disease
6- The prevalence of parasitic infestations: ascariasis and ankylostomiasis are commonly
associated with malnutrition.
7- Metabolic disorders such as galactosemia.
8- Malabsorption syndromes.
9- Endocrinal causes such as diabetes mellitus..
Clinical manifestations of severe marasmus
• Marasmus may occur at any age commonly from birth to 3 years. It is more frequent in infants
than in older children due to rapid rate of growth.
• A child with fully developed picture of marasmus is extremely emaciated, weighing less than
60% of standard weight for age.
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Nutritional disorders
• The infant is very hungry, cries much, sucks his fingers and sleeps little.
• The child is usually alert and looks like a little old man.
• There is loss of subcutaneous fat that leads to a thin wrinkled skin, and skin infection is
common. There is loss of skin elasticity.
• There is marked muscle wasting and the bony prominences are very obvious.
• Mid-arm circumference and skin fold thickness are markedly reduced.
• The chest circumference decreases to less than that of the head.
• The temperature is usually subnormal due to reduction of heat production. Cold extremities
and pulse may be slow.
• The hair is usually not altered, but may be scanty and dry.
• The liver and spleen are usually small in size.
• Constipation is common but diarrhea of infective nature or starvation diarrhea with frequent
small, soft, dark green stools containing mucus may occur.
Classification of marasmus
Marasmus is classified according to the degree of loss of subcutaneous (SC) fat and weight loss.
First-degree marasmus
-Weight for age is 75-90 % of expected weight.
Second-degree marasmus:
-Weight for age is 60-75 % of expected weight.
-A weight-for-length below -2SD of the WHO Child Growth Standards
-A mid-upper arm circumference in children ages 6-59 mo, between115-125mm..
Third-degree maras
- Weight for age is <60 % of expected weight.
-Weight-for-length below -3SD of the WHO Child Growth Standards
-A mid-upper arm circumference in children ages 6-59 mo is,<115mm
Table 6-4 Differences between marasmus and kwashiorkor
Item Marasmus Kwashiorkor
History and examination
- Age Common from 0-3 years 6 mo - 3 yrs

- Anorexia Uncommon, hungry Marked

- Body weight deficit +++ +

- Edema Absent Present

- Muscle wasting +++ +

- Subcutaneous fat Lost Preserved

- Mental changes Irritability Apathy

 Nutritional disorders 57

- Cracky paint dermatosis and Flag sign Absent May be present

of hairs
- - Liver size Not enlarged Enlarged

Laboratory findings
- Plasma albumin level Slightly reduced Markedly reduced

Non-essential/essential amino-acid ratio Normal (less than 2) High

Marasmic kwashiorkor
It is a combined form of severe malnutrition, with clinical signs of both marasmus and
kwashiorkor. Marasmic kwashiorkor usually starts as marasmus with loss of weight more than
40% of standard weight then children are suddenly put on a starchy diet very low in protein, and
signs of kwashiorkor develop such as apathy, anorexia, edema, skin changes and hair changes.
Investigations of malnutrition
1- Blood picture: for type and degree of anemia.
2- Plasma proteins.
3- Blood glucose and serum electrolytes (Na, K, Ca, Mg, zinc) are measured on admission and
throughout recovery.
4- Stool examination: to exclude intestinal helminthes. pH of stool is done to exclude lactose
intolerance.
5- Tuberculin test and x ray chest must be done to exclude tuberculosis which is common in
malnutrition. (See chapter VIII)
6- Blood culture: especially in cases with sepsis.
Complications of malnutrition
1- Dehydration, shock and acid base disturbances as a result of attacks of diarrhea.
2- Electrolyte disturbances: hypocalcemia, hypomagnesemia, hypokalemia, decrease serum
sodium and increase intracellular sodium.
3- Increased susceptibility to infections (bacterial, viral and fungal): such as respiratory,
gastrointestinal, urinary tract infection, otitis media and chronic infections as TB. Decreased
immunity leads to repeated infections. Septicemia is a serious complication that is fatal if
associated with shock, hypothermia and hypoglycemia. Measles is also a fatal disease in the
malnourished infants.
4- Heart failure: it is related to several factors:
a- Low hemoglobin level may result in anemic heart failure.
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Nutritional disorders
b- Excessive intake of salt in diet.
c- Weakened myocardium by nutritional deficiency.
d- Toxic myocarditis secondary to infection.
The impaired cardiac function combined with an expanded blood volume will lead to heart
failure with sudden collapse and peripheral circulatory failure.
5- Hypothermia: related to reduced SC fat, and to deficient energy intake. Unexplained and
prolonged hypothermia may be fatal if associated with hypoglycemia and or septicemia.
6- Hypoglycemia due to starvation, defective glucose metabolism and low glycogen stores in the
liver.
7- Hemorrhagic tendency: is grave and a bad prognostic sign. It is related to several factors:
a- Fragile blood vessels.
b- Deficiency of coagulation factors and platelets.
c- Disseminated intravascular coagulation (DIC): it is due to wide spread intravascular
deposition of fibrin which leads to tissue ischemia and necrosis and consumption coagulopathy
with bleeding tendency.
8- Other non fatal complications:
a- Severe malnutrition in early infancy and childhood may have a permanent retardation in
cognitive development. Attention span, memory, abstract thinking are more prone to be affected
by nutritional deficiencies.
b- Some permanent short stature may occur (nutritional dwarfism).
c- Blindness may occur due to vitamin A deficiency.

Prognosis of severe malnutrition

Under the best conditions, the mortality rate in children with severe malnutrition admitted to
hospitals is still relatively high
Factors that influence prognosis of severe malnutrition Death is related to complications
such as severe dehydration with electrolyte imbalance, heart failure, bronchopneumonia due to
Gram-negative organisms, septicemia, bleeding tendency, hypoglycemia or hypothermia.
Prognosis varies according to age of child, duration and severity of malnutrition. Early treatment
will result in good prognosis.
a- Age of child: the younger the age the poorer the prognosis.
b- Duration and severity of malnutrition: children who suffer acute deficiencies of short
duration seem to recover more rapidly and completely, but those who have had long periods of
 Nutritional disorders 59

severe deficiencies are more liable to develop permanent retardation in physical and mental
development.
Management of malnutrition
Moderate malnutrition:
-There is no need for admission to hospital.
-Good maternal nutritional support.
-Follow guide lines of normal nutrition and weaning of infants and children.
Severe malnutrition:
Severe malnourished children must be admitted to hospital for emergency treatment.
Treatment of the cause:
e.g : T.B and parasitic infestation
Emergency treatment
Observation sheet is used for recording weight, height, temperature, respiratory rate, intake
and output .
1-Treatment of shock
N.B: treatment of malnourished children with shock is different than treatment of well
nourished children ( less rapid, small volume and different fluid)
- Give oxygen.
- I.V 10% glucose (5ml/kg).
- I.V ringer lactate or half normal saline (15 ml/kg) over one hour
- Measure and record pulse every 10 minutes
a) If there are signs of improvement: repeat I.V fluid (15 ml/kg) over one hour then switch to
oral rehydration therapy
b) If there are signs of no improvement: assume septic shock then give maintenance fluids
and fresh whole blood slowly.
2- Treatment of hypoglycemia: (see below)
3-Treatment of severe dehydration :.( see below)
4-Treatment of very severe anemia: give whole blood slowly if Hb < 4 g/dl, if there is heart
failure give packed RBCs, give furosemide at the start of transfusion
5-Treatment of corneal ulceration: give vitamin A and atropine eye drops.
The 10 steps of treatment, which are separated into 2 phases referred to as:
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Nutritional disorders
a - Stabilization: The aim of stabilization phase is to repair cellular function, correct fluid and
electrolyte imbalance, restore homeostasis, and prevent death from hypoglycemia, hypothermia
and infection (steps 1-7 ,table 6/5)
b –Rehabilition : the aim of rehabilitation phase is to restore wasted tissues (i.e., catch-up
growth)
N.B: 3 Fatal mistakes that should be avoided during treatment
- If you focus on the illness and treat as well nourished child.
- If you treat edema with diuretics
- If you give high protein diet in the early phase of treatment

Table6-5: Ten steps of treatment of acute severe malnutrition

Stabilization Rehabilitation
Day 1-2 Day 3-7 Week 2-6
1-prevent/treat hypoglycemia
2- prevent/treat hypothermia
3- prevent/treat dehydration
4-correct imbalance of electrolytes
5-treat infections
6-correct deficiencies of micronutrients No iron With iron
7-start cautious feeding
8-Rebuild waste tissues (catch-up growth)
9-Provide loving care and play
10-Prepare for follow-up

Table 6-6: Therapeutic directions of stabilization steps

Step Prevention Treatment
 Nutritional disorders
1-Prevent/treat a- Frequent feeding
hypoglycemia b- Keep warm
e.g. level< 54 mg/dl c- Treat infections
N.B: hypoglycemia and
hypothermia are signs of severe
infection and often coexist
2-Prevent/treat a- Keep warm and dry.
hypothermia b- feed frequently
Axillary c- treat infections
temperature<35 °C
3-Prevent/treat N.B: It is difficult to estimate
dehydration dehydration status in severely
malnourished child using clinical
signs alone. So assume all
children with watery diarrhea
may have dehydration
a- Replace stool losses by
Rehydration Solution of
Malnourished child "ReSoMal"
(low Na).
b- Keep feeding.
c- Encourage continuation of
breast feeding.
4-correct electrolyte N.B: all severely malnourished
imbalance children have excess intracellular
( K and Mg, body sodium. Extracellular
excess body sodium) sodium may be low
(giving high sodium loads is fatal)
5-Prevent/treat Minimize risk of cross-infection
infections a- Avoid overcrowding
b- Wash hands
6-Correct micronutrient deficiencies: give vitamin A, folic acid, zinc, copper and multivitamins.
N.B: do not give iron in the stabilization phase because iron makes infections worse.
61
If conscious
a- 10%glucose oral
b- Feed frequently
c- Keep warm
d- Start antibiotics
If unconscious
a- I.V glucose 10%
b- Other measures as conscious
a- Feed frequently
b- Skin to skin contact
c- Monitor temperature
 N.B: Do not give I.V fluids unless child
is shocked.
 In severe anorexia and vomiting use
nasogastric tube.
 Electrolyte level may be misleading
because of sodium leaking from blood to
cells and potassium leaking out of cells.
a- Give ReSoMal,
b- Monitoring of pulse and
c- respiratory rate
d- Stop when rehydrated.
a- Give extra potassium and magnesium
for at least 2 weeks.
b- Restriction of salt intake.
a-Give broad spectrum antibiotics to all
children on the first day.
b- Measles vaccine if child is >6months and
not immunized, delay if the child is in
shock. (Because measles is fatal in these
cases).
Note:
 Infections are often silent.
 Pyrexia and leukocytosis may be absent
but sudden changes in conscious level
or hypothermia may indicate
underlying sepsis.
 Avoid steroids as they depress immune
function
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Nutritional disorders
7-Start cautious feeding:
a- Encourage breast feeding beside complementary formula
b- Oral or nasogastric never parentral.
c- Small frequent feeds of low osmolarity and low lactose milk.
d- Give 100-130 ml/kg/day.
e- Milk formula contain
 100kcal/kg/day
 1-1.5 gm protein/kg/day.
f- Weight daily
8-Rehabilitation phase (catch up growth):
The signal to enter this phase is:
 Reduced edema
 Return of appetite
A controlled transition over 2-3 days is recommended. Through this period increase
amount of calories and protein gradually (increase 10 ml/feed as tolerated).
In the rehabilitation phase a vigorous approach to feeding is required to achieve high
intake and rapid weight gain >10 gm gain/kg/day.
After transition give:
 Encourage breast feeding
 Frequent feeds
 Give 200 ml/kg/day
 Milk formula contain
- 150-220 kcal/kg/day
- 4-6 gm protein/kg/day, higher intake of protein is not necessary because exess
protein is utilized for energy, so diet should contain sufficient calories to save
protein for growth.
 Continue to give potassium, magnesium and micronutrient.
 Add iron 3 mg/kg/day
 If the children have good appetite, are clinically well and gained weight, they can
be rehabilitated at home through community based therapeutic care to reduce
exposure to nasocomial infection.
For weaned infants, food needs to be rich in protein easily digestible, low cost and
available.
 Nutritional disorders 63

Animal protein as cheese especially cottage cheese, eggs, yogurt, minced meat may be
given.
Vegetable protein as mixed legumes (e.g. beans, peas, lentils, chick peas) is added to
increase their biological value as they contain different essential amino acids.
Seeds are added as maize and wheat.
9- Provide loving care and play
Children with severe malnutrition have developmental delay, so loving care and structured play,
during and after treatment are essential to aid recovery of brain function.
10- Prepare for follow up after recovery
A child who is 90% weight for height can be considered to have recovered. The child is still
likely to have a low weight for age. Good feeding practices and loving care should be continued at
home.
Show parents how to:
 Feed frequently with energy and nutrient rich foods.
 Give structured play therapy
Signs of recovery
1- Improvement of appetite with decrease of the edema.
2- Increasing alertness and interest in the surroundings.
3- Gradual gain in weight.
Prevention of malnutrition
1- Encouraging prolonged breast-feeding up to 2 years.
2- Use of locally available protein sources as lentils, beans and low cost milk diet as cottage
cheese and yogurt.
3- The best early indication that a child is at risk of poor growth. Supervision of a child’s
progress and recording his growth at a child health clinic are important tools in the early
detection and treatment of malnutrition. This will allow advice and treatment to be given well
before the severe affection occurs.
4- The clinician will also help in prevention of malnutrition by health education, immunization
programs and family planning.
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Rickets
Definition
• Rickets means failure of mineralization of growing bone.
Rickets is found only in growing children before epiphyseal fusion
Classification of rickets
Rickets may be classified as calcium-deficient or phosphate deficient rickets. As both calcium and
phosphate ions comprise bone minerals, insufficiency of either type results in rickets and
osteomalacia. The two types of rickets are distinguishable by their clinical manifestations.
I- Rickets due to calcium deficiency with secondary hyperparathyroidism
1- Lack of vitamin D (vitamin D deficient rickets)
a- Lack of exposure to sunlight.
b- Dietary deficiency of vitamin D.
c- Congenital.
2- Malabsorption of vitamin D.
3- Hepatic disease (hepatic rickets).
4- Renal osteodystrophy.
5- Anticonvulsants drugs.
6- Vitamin D-dependent rickets, type I.

II- Rickets due to primary phosphate deficiency

1- Familial hypophosphatemia.
2- Fanconi syndromes: ( Cystinosis, Tyrosinosis, Lowe syndrome).
3- Renal tubular acidosis, type II proximal.
4- Oncogenous rickets.
5- Phosphate deficiency supply or malabsorption.
III- End organ resistance to 1,25 dihydroxycholecalciferol
Vitamin D-dependent, rickets type II.
IV- Related conditions resembling rickets e.g. hypophosphatasia.

Vitamin D deficient rickets

Metabolism of vitamin D: there are two forms of vitamin D:
1- Vitamin D2 is present in animal source diet such as fish liver oil and egg yolk.
2- Vitamin D3 is found in some diet and in the skin as provitamin (7 dehydrocholesterol) that is
activated by ultraviolet rays of sunlight to cholecalciferol.
Both forms of vitamin D undergo 25 hydroxylation in the liver to 25-hydroxycholecalciferol.
Further hydroxylation takes place in the kidney to 1,25 dihydroxycholecalciferol. This end product
is considered a hormone and it is the active form of vitamin D.
Normal requirements of vitamin D
The usually recommended daily intake of vitamin D is 400 IU in infants less than 1 year and 600
IU in children more than 1 year.
 Nutritional disorders 65

In low birth weight infants, the daily requirement is 1000 IU.

Actions of vitamin D
1- It promotes intestinal absorption of calcium and phosphorus.
2- It increases reabsorption of calcium and phosphorus by kidney tubules.
3- It has a direct effect on mineral metabolism of bone (deposition and resorption). If
vitamin D is deficient, minimal amount of calcium is absorbed from the intestine. Hypocalcemia
stimulates the release of parathormone that leads to mobilization of calcium from bones to the
blood to maintain serum calcium level within normal, with increased excretion of phosphorus in
urine. Therefore when vitamin D is given therapeutically, calcium supplement is needed to avoid
occurrence of tetany.
Sequels of vitamin D deficiency
a- Defective mineralization of osteoid tissue leads to rickets.
b- Low serum phosphorus due to increased level of parathormone hormone which decreases
phosphorus reabsorption from the kidney with increased phosphaturia.
c- Elevated serum alkaline phosphatase due to increased osteoblastic activity.
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Fig. 6-1 Metabolism of vitamin D

Etiology of rickets
1- Decreased vitamin D in the diet. Breast and unfortified cow milk, cereals, vegetables and
fruits contain small amounts of vitamin D.
2- Inadequate direct exposure to ultraviolet rays of the sunlight. These rays do not pass through
ordinary window glass, and dusty atmosphere interferes with the passage of ultraviolet rays.
3- Black children are susceptible to rickets due to inadequate penetration of sunlight through the
skin.
4- Calcium and phosphorus homeostasis depends on intestinal absorption of dietary calcium and
phosphorus. Maximum calcium absorption occurs when the ratio of calcium to phosphorus in
diet is 2:1. Increased phosphate and phytates in diet decrease absorption of calcium.
5- Rapid growth increases the demands for vitamin D as in low birth weight infants and the first
year of life.
6- Malabsorption due to inability to absorb vitamin D, or calcium or both.
 Nutritional disorders 67

7- Anticonvulsant therapy may interfere with metabolism of vitamin D.

8- Congenital vitamin D deficiency: during pregnancy, vitamin D supplied by the mother is
adequate for intrauterine life and for few months after birth. These stores are deficient with
prematurity. In severe maternal deficiency of vitamin D, a rare congenital vitamin D deficiency
of the newborn infant occurs. These infants present with hypocalcaemia.
Rickets is a disease of growing bones and malnutrition causes deceleration or arrest of growth.
The presence of clinical manifestations of rickets in children suffering from malnutrition may be
explained by:
• The rachitic process preceded malnutrition (clinically bony changes persist for months or
years).
• malnutrition decreases the intestinal absorption of vitamin D and calcium with marked
deficiency of vitamin D supply, rickets may occur.
• malnutrition may be present in cases of vitamin D resistant rickets.
Pathology
Normally, there are two types of ossifications, endochondral and subperiosteal.
In long bones, endochondral ossification occurs at the growing ends of bones and leads to increase
in length while subperiosteal ossification leads to increase in thickness of the bone.
Osteoblasts deposit osteoid tissue matrix that is rapidly mineralized by deposition of calcium and
phosphorus.
At the growing end of bone, normally there are 4 zones
1- Zone of resting cartilage: formed of one layer of cells.
2- Zone of proliferating cartilage: formed of 5-6 rows of cells and arranged in regular columns.
It is avascular and free of calcium.
3- Zone of provisional line of calcification: old cartilage cells degenerate and calcium salts are
deposited in this layer. It is a thin area and it appears in the x-ray as a straight white line.
4- Zone of ossification: it is invaded by capillaries. Osteoblasts are formed and deposit a layer of
osteoid tissue that is rapidly mineralized by deposition of calcium and phosphorus.
Pathological changes in rickets
At the growing ends of bones the following changes occur:
Zone of resting cartilage: shows no change.
In the zone of proliferating cartilage: there is excessive proliferation of cartilage cells and they
fail to arrange themselves in columns. They are irregular, and fail to complete their normal cycle
of proliferation and degeneration.
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In the zone of provisional calcification: there is lack of calcification and it appears as irregular,
cupped and frayed area in radiogram.
In the zone of ossification: the osteoid tissue is not mineralized.
These changes result in wide irregular area of non-calcified cartilage and osteoid tissue (rachitic
metaphysis). It is less rigid than normal bone. This zone is responsible for many skeletal
deformities. It is compressed and bulged laterally producing flaring of ends of long bones and
rachitic rosaries.
• Regarding subperiosteal bone growth, there is defective mineralization of the outer newly
formed bone.
• There is rarefaction of the shaft that leads to deformities and fractures.
• There is excessive deposition of uncalcified matrix around ossific centers of flat bones e.g.
cranial bones.
Clinical manifestations of rickets
Age incidence: 3 months - 3 years.
A- Early clinical signs
1- Craniotabes: it is due to thinning and softening of the outer table of the skull bones and it is
detected by pressing firmly over the occiput or posterior parietal bone eliciting ping-pong ball
sensation. It is rarely present after 8 months of age.
2- Flaring of ends of the long bones.
a- Broad ends of radius and ulna.
b- Marfan sign: flaring of the lower tibial metaphyses forms a prominence above the normal
prominence of medial malleolus with a relative groove in between.
c - Rosary beads: they are due to enlargement of costo-chondral junctions. They are palpable.
3- Increased sweating around the head may be present.
B- Clinical signs of advanced rickets
1- Head
• Softness of the skull may cause asymmetry of the head with flattening of sites of continuous
pressure.
• The head may be larger than normal.
• There is bossing of the parietal and frontal bones due to excessive osteoid tissue. The head has
a box like appearance (caput quadratum).
• Delayed closure of anterior fontanel.
• Delayed eruption of teeth with defective enamel and tendency to develop caries.
2- Thorax
• Rosary beads: they are both palpable and visible.
 Nutritional disorders 69

• Pigeon chest: the sternum with its adjacent cartilage appears to be projecting forwards.
• Vertical grooves (longitudinal grooves): these sulci are seen posterior to rosary beads due to
yielding of the chest wall at the weakest points i.e. the costochondral junctions under the effect
of atmospheric pressure.
• Harrison sulcus:a horizontal groove at the lower border of the chest along the costal insertion
of the diaphragm. The sulcus is the result of pulling of the diaphragm on soft ribs at the site of its
insertion.
3- Abdomen
• Displacement of liver and spleen downward due to thoracic deformity.
• Potbelly abdomen and constipation may occur due to hypotonia of abdominal and intestinal
muscles.
4- Spinal column: dorsal kyphosis appears during sitting and disappears when the child is pulled-
up by his arms (postural kyphosis). Scoliosis and lumbar lordosis may also occur.
5- Pelvis: contracted inlet and outlet may be present. Pelvic deformities may be responsible for
difficult labor in females and may necessitate cesarean section.
6- Extremities
• Enlargement of ends of bones: This may be visible.
• Bow legs (Genu varum) and knock knees (genu valgum).
• Fractures (complete or greenstick).
7- Muscles: muscle weakness and hypotonia are common causes of delayed motor activities as
delayed sitting, standing and walking.
8- Rachitic dwarfism: deformities of spine, pelvis and legs result in short stature.
9- Ligaments: relaxation of ligaments helps in the production of abnormal range of joint
movement and deformities.
Complications
1- Capacity of the chest to expand is limited by chest deformities. This increases the
susceptibility to respiratory infections and atelectasis.
2- Anemia may be due to iron deficiency.
3- There are bouts of diarrhea alternating with constipation.
4- Tetany occurs when total serum calcium level decreases below 7 mg/dL or when ionized
calcium is below 3 mg/dL.
5- In advanced cases, permanent bone deformities may occur.
Diagnosis
A- By clinical manifestations
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B- Biochemical changes
1- Increased phosphaturia.
2- Low serum phosphorus level (normal range: 4.5-6.5 mg/dL).
3- High alkaline phosphatase level (normally up to 450 U/L).
4- Serum calcium level is usually normal. Hypocalcemia may occur in advanced untreated cases.
C- Radiological changes
The lower ends of radius and ulna give the best information because they are readily accessible,
surrounded by thin tissue and site of rapid growth.
a- Active rickets
• Increased distance between the calcified part of metaphyses and the centers of ossification.
This is a result of increased thickness of uncalcified portion of the bone that does not appear on
x-ray.
• Flaring of metaphyseal ends due to massive formation of cartilagenous and osteoid tissue.
• Cupping of metaphyseal plate because it is soft and easily compressed.
• Fraying of the distal ends of bones: replacement of zone of provisional calcification that is
normally linear by a broad irregular zone.
• Decreased density of the shaft.
• Double contour appearance of the shaft, the less calcified recently deposited osteoid surrounds
the older more calcified tissue.
• Fractures may be present. They may be complete or incomplete (green stick fractures).
b- Healing rickets
Deposition of calcium in zone of provisional line of calcification. This line is separated from distal
end of the shaft by a zone of decreased calcification.
c- Healed rickets
• The calcification starts from the shaft of bones and progresses to involve the metaphyses.
• The last part to be mineralized is the metaphyses adjacent to zone of provisional calcification.
• The shaft becomes united with provisional line of calcification. Healing is complete and it is
termed “healed rickets”.
• Flaring, cupping and other bone deformities may remain and this takes months or years to be
corrected by a process of re-modeling during bone growth.
Assessment of healing of rickets
If vitamin D is given in adequate dose, healing will occur within 2-4 weeks and can be assessed by:
1- Clinical manifestations
 Nutritional disorders 71

• Disappearance of hypotonia: improvement of motor activities, (the child is able to sit, stand or
walk), disappearance of potbelly abdomen, kyphosis and constipation.
• Disappearance of craniotabes.
• The child may start teeth eruption.
2- Biochemical manifestations: the earliest signs of recovery are decreased level of phosphorus
in urine and increased serum phosphorus level. Alkaline phosphatase then drops.
3- Radiological manifestations: linear deposition of calcium in provisional line of calcification.
Differential diagnosis
1- Vitamin D deficient rickets must be differentiated from vitamin D resistant form by the
dramatic response to the usual therapeutic doses of vitamin D.
2- Rachitic craniotabes should be differentiated from other causes of craniotabes such as:
a- Physiologic craniotabes that occurs adjacent to suture lines in low birth weight infants and in
the first 3 months of life.
b- Hydrocephalus.
3- Rachitic rosaries should be differentiated from those of achondroplasia and scurvy and from
pseudo-rosaries of marasmus.
4- Delayed motor activities in rickets should be differentiated from other causes.

Prevention
Most cases of nutritional rickrts can be prevented by universal administration of 400 IU of vitamin
D to infants who are breastfed. Older children should receive 600 IU/day.
Treatment
Previous administration of vitamin D should be inquired about in the history to avoid
hypervitaminosis D. When rickets is complicated by tetany, tetany should be treated at first.
• Oral administration of vitamin D in a dose of 2000 -5000 IU per day in 3 divided doses. This
will produce healing within 4 weeks.
• Stoss therapy:300.000 – 600.000 IU of vitamin D is administered I.M as 2-4 doses over 1 day
or IM injection of 200.000 IU every week for three doses
• Elemental calcium is given in a dose of 30-75 mg/kg (start at higher dose and wean down to the
lower end of the range over 2- 6 weeks).
•Calcium and phosphorus administration can be given as dietary intake of fortified milk and milk
products.
After complete healing, the dose of vitamin D should be reduced to 400 -600 IU/day.
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Hypervitaminosis D
It results from administration of excessive amounts of vitamin D. Features develop after 1-3
months of administration of large doses of vitamin D.
Clinical and laboratory features
Anorexia, vomiting, hypotonia, constipation, polyuria, polydipsia, dehydration, hypertension,
retinopathy, clouding of the cornea, renal damage, metastatic calcifications, hypercalcemia and
hypercalciuria.
Treatment
• Discontinuation of vitamin D intake.
• Restriction of intake of calcium.
• For severe cases: aluminium hydroxide by mouth, or sodium versenate as calcium chelating
agents may be used. Corticosteroid therapy may also be used

Tetany
Definition
It is a state of hyperexcitability of the central and peripheral nervous system.
Causes
Hypocalcemia, hypomagnesemia and alkalosis.
I- Hypocalcemic tetany
Calcium in blood is present in plasma. The normal serum total calcium value is 9-11mg/dL. It is
present in the following forms:
(a) Ionized calcium is about 50% of serum total calcium.
(b) Calcium bounds to serum proteins, principally albumin is about 40%.
(c) Calcium bounds to serum anions, mostly phosphate, citrate and sulphate is about 10%.
Ionized calcium is the only biologically available form of calcium. Its level is 4.8 mg/dL. Tetany
develops if total serum calcium level is below 7mg/dL or when ionized calcium is below 3 mg/dL.
Causes
A- In neonatal period: hypocalcemia is mainly due to transient hypoparathyroidism, parathyroid
gland being not fully mature. Increased calcium in fetal life-from physiologic maternal
hyperparathyroidism- may inhibit parathyroid gland in the fetus.
Neonatal hypocalcemia is classified into:
1- Early onset hypocalcemia (during the first 3 days):
a- Low birth weight infants.
b- Infant of diabetic mother.
 Nutritional disorders 73

c- Birth asphyxia.
2- Late onset hypocalcemia: (usually presents at the end of the first week).
a- Congenital vitamin D deficiency. b- Malabsorption.
c- Administration of cow’s milk to newborn infants due to increased phosphate load and
inability of the kidney to excrete phosphate.
B - In children
1- Rickets.
2- Chronic renal insufficiency with marked hyperphosphatemia because increased phosphate
combines with ionized calcium and forms calcium phosphate-protein complex.
3- Diarrhea especially if it is complicated by calcium depletion.
4- Malnutrition, where hypocalcemia is common.
5- Following transfusion of large volumes of citrated blood as in exchange transfusion as citrate
chelates ionized calcium.
6- Hypoparathyroidism.
II- Hypomagnesemic tetany
Normal serum magnesium level ranges from 1.6-2.6 mg/dL. Tetany develops when total serum
magnesium level declines below 1.3 mg/dL.
Causes
1- Impaired absorption of magnesium from the intestine.
2- Persistent diarrhea.
3- Malnutrition.
4- Prolonged parenteral fluid therapy.
5- Hypoparathyroidism. Serum magnesium as well as calcium are both reduced.

III- Alkalotic tetany

Reduction in hydrogen ion concentration results in tetany because it decreases the ionized calcium
Causes
1- Persistent vomiting as in cases with hypertrophic pyloric stenosis.
2- Administration of large doses of sodium bicarbonate.
3- Hyperventilation due to increased CO2 wash.
Clinical manifestations of tetany
Clinical manifestations of manifest tetany
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1-Carpopedal spasm: abduction of hands, flexion of the wrist, flexion of the
metacarpophalangeal joints, extension of interphalangeal joints and adduction of the thumb. Feet
are extended, with the sole cupped and toes flexed.
2- Laryngismus stridulous: laryngospasm may cause suffocation, due to laryngeal obstruction.
3- Convulsions: they are usually generalized and brief. There are no abnormal neurologic
manifestations between the attacks.
Signs of latent tetany
These latent signs may be elicited when manifest tetany is not present. Mechanical, ischemic or
electric stimulation of motor nerves are required to elicit tetany.
1- Chvostek sign (mechanical stimulation), tap on the facial nerve (anterior to external auditory
meatus). The response is contraction of orbicularis oris. It is not considered as sign of tetany in
newborn infants.
2- Peroneal sign (mechanical stimulation), tap on peroneal nerve (just below or over the head of
fibula). This leads to dorsiflexion and abduction of foot.
3- Trousseau sign (ischemic stimulation), a blood pressure cuff on arm is inflated above systolic
blood pressure for 3 minutes, carpal spasm develops.
4- Erb sign (electric stimulation), electrical stimulation by galvanic currents less than that
required for stimulation of muscles under physiologic condition produces muscle contraction.
Treatment
Treatment of the cause.
1- Hypocalcemic tetany
IV injection of calcium gluconate 10% solution. Tissue necrosis may occur if solution is given IM
or extravasates. The dose is 2ml / kg (18 mg/kg elemental calcium). Calcium solution should be
given IV very slowly with continuous intravenous drip with monitoring the heartbeats to avoid
bradycardia or cardiac arrest. There is a dramatic response immediately after calcium injection.
The dose may be repeated every 8 hours until serum calcium level reaches normal values.
I.V therapy should be followed by oral medication . Elemental calcium is given in a dose of 30-75
mg/kg (start at higher dose and wean down to the lower end of the range over 2- 6 weeks).
2- Hypomagnesemic tetany
 IM injection of magnesium sulfate in a dose of 0.2ml / kg of 50% solution. This dose may be
repeated every 6 hr for 3-4 doses.
3- Alkalotic tetany
a- Hyperventilation is treated by rebreathing in a bag to increase Pco 2 concentration.
b- Metabolic alkalosis is treated by giving ammonium chloride.
 Nutritional disorders 75

c- Surgical treatment for cases with pyloric stenosis.

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THE NEWBORN INFANT

Neonatal hyperbilirubinemia
The normal adult serum bilirubin is less than 1mg/dL. Adults appear jaundiced when the serum
bilirubin is greater than 2 mg/dL, while newborns appear jaundiced when the serum bilirubin is
greater than 7 mg/dL due to increased number of red blood cells. Jaundice is observed during the
1st week of life in about 60% of term infants and 80% of pre-term infants.
Bilirubin metabolism
Most of bilirubin is produced from the breakdown of heme portion of erythrocyte hemoglobin.
The remaining 15% to 25% of bilirubin is derived from non erythroid heme proteins (marrow and
extramedullary).
Bilirubin metabolism is initiated in the reticuloendothelial system as old or abnormal red blood
cells are removed from the circulation. This bilirubin in its unconjugated or indirect form is
released into the plasma.

Transport
Bilirubin bound to plasma albumin is carried to the liver and transported into the hepatocyte.
Intracellulary, bilirubin is bound to ligandin (Y and Z proteins).
Conjugation
Conjugation occurs within the smooth endoplasmic reticulum of the liver cell. This reaction is
catalyzed by the enzyme glucuronyl transferase.
Excretion
Conjugated bilirubin is excreted in bile and reaches the gastrointestinal tract, intestinal flora
reduces most of it to stercobilinogen and is then eliminated in stool. Remaining conjugated
bilirubin may be converted back to unconjugated bilirubin by the intestinal enzyme beta-
glucouronidase. Reabsorption of bilirubin from the gastrointestinal tract into the circulation back
to the liver for reconjugation is called enterohepatic circulation.
Causes of neonatal hyperbilirubinemia are shown in table 7-5.
 Nutritional disorders 77

Table 7-5 Causes of neonatal jaundice

U nco nj ug ated Mixed Conjugated hyperbilirubinemia
hyperbilirubine mia hyperbilirubine mia
Hemolytic jaundice Abnormalities of liver cells Decreased rate of excretion
a- Rh and ABO incompatibilities a- Neonatal hepatitis a- Congenital biliary atresia
b- Spherocytosis. b- Infections: TORCH, b- Obstruction due to pressure on
c- Red cell enzyme defects neonatal sepsis. biliary passages by tumor or cyst.
(e.g.G6PD deficiency)
d- Drugs (e.g. excess Vit. k).
e- Cephalhematoma.
Defective conjugation
a- Physiologic jaundice.
b- Crigler-Najjar syndrome.
c- Congenital hypothyroidism.
d- Breast milk jaundice.
Causes of neonatal hyperbilirubinemia according to the age of onset
1- Jaundice, that is present at birth or appears within the first 24 hr of life
a- Rh and ABO incompatibilities (this must be considered till proved otherwise).
b- Cephalhematoma.
c- Intrauterine infection: toxoplasmosis, rubella, cytomegalovirus, herpes simplex (TORCH).
d- Neonatal sepsis.

2- Jaundice that first appears on the 2nd or 3rd day

a- Physiological jaundice.
b- Familial non hemolytic icterus (Crigler-Najjar syndrome). It is a genetically inherited disease
due to deficiency of the enzyme glucuoronyl tansferase.
c- Neonatal sepsis.
3- Jaundice appearing after the 3rd day and within the first week
a- Neonatal sepsis.
b- TORCH infection.
c- Extensive body ecchymosis.
4- Jaundice appearing after the first week of life
a- Neonatal sepsis. b- Neonatal hepatitis.
c- Biliary atresia. d- Breast milk jaundice.
e- Hypothyroidism. f- Spherocytosis.
g- Red cells enzyme defects (e.g. G6PD) deficiency.
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Nutritional disorders
h- Galactosemia (inborn error of galactose metabolism).
5- Persistent jaundice after 2 weeks of life
a - Neonatal hepatitis. b- Biliary atresia.
c- Cytomegalic inclusion disease, $, toxoplasmosis. d- Congenital hypothyroidism.
e- Inspissated bile syndrome (following severe hemolytic disease).
Physiological jaundice
A large proportion of healthy newborns develop jaundice due to increased bilirubin production
following breakdown of fetal red blood cells and due to transient immaturity of the hepatic
glucoronyl transferase enzyme necessary for conjugation of bilirubin.
Clinical Manifestations of Physiological jaundice:
1- Onset at 2nd or 3rd day of life.
2- Disappears at the age of 7-10 days.
3- Infants are healthy with no abnormal physical signs.
Jaundice associated with breast-feeding
Breast milk Jaundice
The milk of some mothers contains substances that may competitively inhibit glucoronyl
transferase enzyme activity.

Clinical picture
The infants develop significant indirect hyperbilirubinemia reaching maximum concentration (10-
30mg/dL) during the 2nd-3rd week. If nursing is discontinued for 48 hours, the serum bilirubin
falls.
Hemolytic disease of the newborn
This term denotes a hemolytic process due to Rh or A B O incompatibilities.
Rh isoimmuization: the mother is Rh-negative and the fetus is Rh-positive (inherited from Rh-
positive father). The problem occurs after the mother has been sensitized by either mismatched
blood transfusion or from fetal blood entering her circulation during a previous Rh-positive
pregnancy at delivery or abortion.
The mother reacts to the fetal blood by producing antibodies that cross the placenta to attack and
hemolyse the red cells in the fetal circulation. In general, the first Rh-positive baby is usually not
affected and the condition becomes more severe in successive Rh-positive pregnancies.
ABO incompatibility is more common than Rh incompatibility. The mother is usually group O
and the baby is group A or B.
 Nutritional disorders 79

Clinical manifestations of severe hemolytic disease

Icterus gravis neonatorum: the hemolysis is marked and jaundice due to rise of unconjugated
bilirubin develops in the first 24 hr after birth and may reach dangerous level leading to
kernicterus. There is marked anemia and hepatosplenomegaly.
Hydrops fetalis (Erythroblastosis fetalis): it denotes the most severe clinical form of hemolytic
disease of the newborn. The fetus is delivered prematurely either as hydropic, stillbirth or as an
edematous anemic live birth that survives only for few hours.
Prevention of Rh incompatibility hemolytic disease
Rhesus hemolytic disease is a preventable condition by giving anti-D globulin (200 μg IM) within
72 hours to all Rh-negative mothers who deliver Rh-positive infants or after abortion.

Table 7-6 Differences between physiological and pathological jaundice

Item Physiological jaundice Pathological jaundice

Onset 2 –3 day in term infant
nd rd
At any time in neonatal period

Level of total bilirubin Up to13 mg/dL. >13mg/dL.

Hyper bilirubinemia Indirect Direct, indirect or mixed

Rate of accumulation <5mg/dL/ 24 hr >5mg/dL/ 24hr

of bilirubin
Duration of jaundice 7-10 days of age in full term and Jaundice may persist after the 2nd wk of
14 days in pre-term life

Examination Good general condition Abnormal manifestations according to

the cause e.g. clay colored stool, pallor,
petechiae or hepatosplenomegaly.

Prognosis Good Kernicterus may complicate untreated

unconjugated hyperbilirubinemia.

Kernicterus (bilirubin encephalopathy)

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The unconjugated, fat soluble, bilirubin is toxic to the developing brain. Kernicterus develops
when unconjugated bilirubin passes the blood brain barrier and is deposited in the brain cells
particularly the basal ganglia. This occurs when the levels of unconjugated bilirubin exceeds
20mg/dL in term infants but at somewhat lower levels in pre-term and those suffering from
asphyxia or sepsis.
The earliest clinical manifestations include: poor feeding, lethargy, hypotonia, high-pitched cry
and poor reflexes.
Later, convulsions, bulging fontanel and hypertonicity are evident.
Kernicterus usually ends in death and those who survive are left with choreoathetoid cerebral
palsy, mental retardation or nerve deafness.
Direct or conjugated hyperbilirubinemia
It is due to failure to excrete conjugated bilirubin from the hepatocyte into the duodenum. It
manifests by a conjugated bilirubin over 1.5 mg/dL. It may be associated with hepatomegaly,
splenomegaly, pale stools and dark urine. Conjugated bilirubin is found in urine.
Causes of direct hyperbilirubinemia
1- Liver cell injury: e.g. neonatal hepatitis.
2- Biliary atresia (intra or extrahepatic), choledochal cyst, stenosis of bile duct or inspissated bile
syndrome (secondary to increased bilirubin load).
Table 7-7 Differences between neonatal hepatitis and biliary atresia
Item Neonatal hepatitis Biliary atresia
Stool color Intermittent or transient pale stools Persistent pale stools
Investigations
- Serum bilirubin Biphasic Mainly direct
- SGOT.SGPT Marked Increase Mild increase
- Alkaline phosphatase Mild increase Marked increase

Hepatobiliary scintegraphy Sluggish uptake, but excretion of the Hepatocyte function is intact and
isotope into the biliary tract and unimpaired uptake, but excretion
intestine eventually occurs. into the intestine is absent.

Sonography of the liver No dilatation of biliary tree Dilatation present in patients with
extra hepatic biliary atrezia

Liver biopsy Shows distortion of lobular The basic hepatic lobular

architecture, marked infiltration architecture is intact but there are
with inflammatory cells and focal bile ductular proliferation,
hepatocellular necrosis. perilobular edema and fibrosis
Investigations of neonatal hyperbilirubinemia
1- Serum bilirubin (direct-indirect) level should be monitored at regular intervals.
2- Low Hb level and increased reticulocyte count suggest hemolysis.
3- Blood group Rh and ABO typing.
4- Coomb’s test: it is positive in isoimmunization (e.g. Rh or ABO).
 Nutritional disorders 81

5- Specific tests: blood culture, liver function tests, red cell enzyme studies, serology for
common intrauterine infections (TORCH).
6- Ultrasonography and isotope scanning.
7- Liver biopsy.
Treatment of neonatal jaundice
The aim is to correct the etiologic condition and to bring down the level of serum bilirubin to
prevent kernicterus. In physiologic jaundice close observation is usually all what is needed. Early
feeding and adequate hydration help the liver to conjugate bilirubin efficiently.
1- Phototherapy should be started if the bilirubin level continues to rise. This involves exposing
the infant to light (usually with a wave length around 450 nm). Photodegradation converts
bilirubin to a non-toxic water-soluble product that is excreted in urine. The eyes of the infants
should be covered and care is needed for temperature control and fluid balance.
2- Exchange transfusion: when unconjugated bilirubin ≥ 20 mg /dL in term infant in spite of
phototherapy, exchange transfusion is performed. In preterm infants exchange transfusion may
be done at lower levels of bilirubin. An exchange of approximately 2 blood volumes of the
infant (2 X 85ml/kg) is needed.
3- Intravenous immunoglobulin (IVIG): used in hemolytic jaundice, early administration of
IVIG may reduce hemolysis, peak serum bilirubin levels, the need for exchange transfusion,
duration of phototherapy, and the length of hospitalization. A single dose of 0.5-1 gm/kg may
be used.
4- Treatment of chronic cholestasis: a major concern is growth failure due to malabsorption
and malnutrition resulting from ineffective digestion and absorption of dietary fat. Usage of a
medium-chain triglyceride-containing formula, replacement of fat soluble vitamins (A,D,E and
K) and micronutrients (ca, phosphate, zinc) may improve caloric balance.
Surgical interference may be needed. Liver transplantation is indicated in patients with
advanced liver disease.