Methodical Instruction for Students homework
Theme: Peculiarities of the protein metabolism, semiotics of its
disturbances in children
Aim: To know etiology and pathogenesis of peculiarities of the protein
and metabolism, semiotics of its disturbances in children , to be able to
put the diagnosis of malnutrition on the base of diagnostic criteria, to prescribe
therapy, and prophylactic measures.
Students Professional Orientation.
Millions of infants and children throughout the world suffer and die each year
from lack or inadequate nourishment. The highest incidence of this morbidity and
mortality is in the technically underdeveloped countries where social, economic,
sanitary and educational factors are important contributors. The decrease in the
breast feeding in the absence of a cheap , acceptable and sanitary substitute is
perhaps the most important single factor. Intercurrent infections, particularly the
gastrointestinal tract, are the major constributor to morbidity and mortality.
Peculiarities of the protein metabolism, semiotics of its
disturbances in children is absence of adequate caloric and volume feeding of
the child There are numerous causes of malnutrition including recurrent bacterial
diarrhea, often upper respiratory tract infections, congenital gastrointestinal
diseases, diseases of the mother during pregnansy. This state is associated with
anergy, infectious complications, high mortality.
Basic Level.
Categories of Common Metabolic Disorders
Category
Disorders of amino acid metabolism
Mucopolysaccharidoses
Common Examples
Phenylcetonuria, homocystinuria, celiac
disease
Marfan syndrome, Mucopolysaccharidos
1. Etiology: inadequate feeding, low level of ferments of gastrointestinal tract.
Organic factors include congenital heart defects, neurologic lesions, microcephaly,
chronic urinary tract infection, gastroesophageal reflux, renal insufficiency,
endocrine dysfunction, cystic fibrosis. Malnutrition can also be caused by
psychosocial factors, the problem being between the child and primary caregiver,
usually the mother. In this situation the lack of physical growth and development is
secondary to the lack of emotional and sensory stimulation.
Pathogenesis: Digestive defects mainly include those conditions in which the
enzymes, necessary for digestion are diminished or absent, such as cystic fibrosis,
in which pancreatic enzymes are absent; biliary or liver disease, in which bile
production is affected, or lactase deficiency, in which there is congenital or
secondary lactose intolerance. Absorptive defects include those conditions in
which the intestinal mucosal transport system is impaired. It may be because of
primary defect such as celiac disease or gluten enteropathy or secondary to
inflammatory disease of the bowel, that results in impaired absorption because
bowel motility is accelerated. Anatomic defects such as short bowel syndrome,
affect digestion by decreasing the transit time of substances with the digestive
juices and affect absorption by compromising the absorptive surface. All this
causes leads to maldigestion and malabsorption syndrome, damage of
function of all organs and systems of the organism.
2. Main clinical symptoms are: abdomen pain, regurgitation, periodic
vomiting, bad appetite, frequent liquid stool, decreasing or absense of
subcutaneous fat. Becides the obvious signs of malnutrition and delayed
development, the child seems to have a characteristic posture of “body language”.
The child may be unpliable, stiff and rigid. He is uncomforted by unyielding to
cuddling and is very slow in smiling or social responding to others. The other
extreme is the floppy infant, who is like the rag doll.
Frequently there is a history of difficult feeding, vomiting, sleep
disturbances, excessive irritability. Difficulties of infant feeding may include poor
appetite, poor suck, crying during feeding, vomiting, hoarding food in the mouth,
ruminating after feeding, refuse of liquids and solids, aversion behavior such as
turning from food or spitting food. In addition, chronic reduction in caloric intake
can lead to appetite depression, which compounds the problem. Another
outstanding feature of children with malnutrition is their irregularity in activities of
daily living. Some of these children called as “difficult child pattern”. However,
another type is the passive, sleepy, lethargic child who does not awake up for
feeding.
Other clinical symptoms range from moderate growth failure ( a common
occurance in underdeveloped countries ) to more severe conditions such as
marasmus and kwashiorcor. The former results from an anadequate intake of a
suitable diet; the latter resulrs from a diet with a low protein, energy ratio,
frequently with protein of poor biologic quality. The three stages of proteinenergy
malnutrition
are
marasmus,
marasmic-kwashiorcor
and
kwashiorcor.They are compounded by a whole spectrum of nutritional disorders
that include deficiences of one or more vitamins, minerals and trace minerals. The
three stages of protein-energy malnutrition can be differenciated most clearly on
the basis of clinical findings. Intermediate forms known as marasmic-kwashiorcor
also are seen. Growth retardation, weight loss, psychic changers, muscular atrophy,
pellagroid dermatitis, hair changes, edema, gastrointestinal changers and other
abnormalities are present in various combinations. Marasmus which predominate
in infancy, is characterised by severe weight reduction , gross wasting of muscle
and subcutaneous tissue, no detectable edema and marked stunting. Marasmus
results from inadequate energy intake, impaired absorption of protein, energy,
vitamins and minerals. The hair and skin changes and hepatomegaly resulting from
fatty infiltration of the liver. The marasmic child, characteristically irritable and
apathetic, is the skin and bones portrait of the skeleton.
Kwashiorcor results from either inadequate protein
intake , or, more
commonly, from acute or chronic infection. It appears predominantly in older
infants and younger children. Clinically it is characterised by edema, skin lesions,
hair changers, apathy, anorexia, a large fatty liver, and decreased a serum
albumine. Weight loos is also usual, without a decrease of energy intake. The
edema of kwashiorcor can only partially be explained by the low serum albumine,
other contributing factors include increased capillary permeability, increase
cortisol, and antidiuretic hormones lewel.
Marasmic – Kwashiorcor presents with the clinical findings of both
marasmus and kwashiorcor. The child has edema, gross wasting and usually
stunted. There may also be mild hair and skin changers and a palpable fattyinfiltrated liver. The child with marasmus-kwashiorcor is one who demonstrated
the combined defects of an inadequate intake of nutrients to meet requirements
plus superimposed infection.
3. General examination of the patient: patients have asthenic constitution,
reduced degree of nourishment, weight loss, the abdomen is great, distended,
meteorism, the skin and mucus membranes are dry, turgor of skin is decreased,
muscular hypotonia, abdomen is asymmetrical, CNS dysfunktion (retardation of
the development).
4. Classification: malnutrition of the I stage - weight loss on 10-20%;
II stage - weight loss on 20-30%;
III stage - weight loss 30% and more.
I stage – 10-20% weight loss.
The general condition of the patient is satisfactory; Psychomotorical
development is adequate to age; coefficient weight / length is about 5560;proportion index changes; the index degree of nourishment of Chulitskaya
reduces to 10-15; skin elastisity and turgor moderately reduced also.Subcutaneous
fat on abdomen 0.8-1 sm.
II stage – 20-30% weight loss.
State of moderate severity; pallorness, dryiness of the skin; psychomotorical
development is reduced; muskle hypotonia, Decreasing of appetite, vomiting;
coefficient weight / length low than 56; proportion index changes; the index degree
of nourishment of Chulitskaya reduces to 0-10; polyhypovitaminosis, anemia,
hypo and dysproteinemia; signs of rickets; frequent intercurrent infections with
poor symptoms. Decreases immunologic reactivity.
III stage – more than 30% weight loss.
General state of the patient is grave, severe emaciation, cachexia,
subcutaneous fat is absent, menthal retardation, somnolents, athrophy of the
muscles, temperature of the body is low, regurgitation, vomiting, frequent stools,
weight loss more than 30%, lenght loss – more than 4 sm, the index degree of
nourishement of Chulitskaya is negative, skin elastisity and turgor are absent, skin
and mucus are very dry, great abdomen, breathing is difficult. Heart beats are
quiet, bradycardia, immunologic reactivity paralyses, all systems and organs are
impaired – anemia, rickets, bacterial infections.
Malnourished children are clearly more susceptible to infection. The
consequent interaction of infection with malnutrition is one of the major factors of
the increased morbidity and mortality. Many authors demonstrated that nutritional
deficiency was associated with 60,9% of the death from infectious diseases.
Diarrhea and measles were the diseases with the greatest morbidity and mortality
in which malnutrition was the main factor. The mechanism by which infection
leads to a malnourished child include a) anorexia; b) replacement of solid foods
with a low-energy, low-protein diet; c) decreased nutrient absorption resulting
from diarrhea and intestinal parasites; d) increased urinary losses of nitrogen,
potassium, magnesium, zinc, phosphate, sulfur and vitamins A, C, B2. Increased
urinary nitrogen excretion results from an increased mobilisation of amino asids
from peripheral muscle for gluconeogenesis in the liver with a deamination and
exretion of nitrogen in the form of the urea. Without an increased dietary intake, to
compensate for losses, a kwashiorcor-like syndrome results. Despite the
mobilisation of aminoasids from peripheral muscle, there is also the decrease in
whole blood amino acids after the exposure to an infectious agent. An increased
synthesis of acute-phase reactants, including haptoglobin, C-reactive protein, aantitrypsin, a2-macroglobulin, also occurs.
Diagnosis I. Damage of growth and development of the child
II. peripheral blood : leukocytosis with a prepoderanse ofneutrophils electrolyte
losses acidosis, hyponatremia, hypoalbuminemia polyhipovitaminoses, anemia,
low level of ferments, low level of T-, B-lymphocytes and immunoglobulines .
III. Stool examination for blood, leukocytes, pH, fat, reducing sugars or parasites;
IV.Culture of stool, urine and blood.
Children with protein-energy malnutrition may have either hypochromic
microcytic or normochromic normocytic anemia, which is the result of defective
hemoglobine synthesis. Infection also affects the endocrine system. Changes in
hormone levels occur simultaneously with infection and precede the changes in
amino acids.
During diarrhea, it is significant loss of potassium and magnesium in the
stools, leadind to a decrease in serum electrolytes. There is also urinary loss of
electrolytes as a result of increased muscle breakdown. Iron absorption and
methabolism are also affected by infection. Infections such as malaria and typhoid
may cause increased hemolysis and resultant acute hemolytic anemia.
5. Therapy: may be prescribed dietary support: yogurt, provision ofaproteine
hydrolysate formula, increasing fluid intake, administration of broad-spectrum
antibiotics in the case of infections, central venous hyperalimentation. The
nutritional support must provide adequate calories to meet metabolic
needs.Vitamines, ferments, anabolic hormones are also may be given. Treatment
consists of feeding adequate amounts of both calories and protein in a form
accepted and tolerated by the infant and measures to combat intercurrent infection.
Although the mortality rate is high, the response of the infants and young children
who do recover is gratifyingly rapid. Nitrogen is retained with great efficiency, and
"catch-up" growth readily occurs. The ratio of protein to calories in the diet need
be no different from that in normal diets; 10 to 15% of calories should come from
protein. Prevention of infant malnutrition is one of the largest challenges faced by
child health workers in the world. Diarrhea
malnutrition.
frequently accompanies severe
Failure To Thrive
Failure to thrive secondary to so-called environmental deprivation is a broad
term used to describe a distortion of physical, social, emotional, or other aspects of
somatic and psychic growth in poorly mothered children. The term implies more
than simply failure to grow.4 Infants and children with this condition have values
for height and weight below the 5th percentile on the NCHS Growth Charts (see
Appendix A). Their families are characterized by marital strife and financial
instability. Public welfare assistance is common, as is overcrowded and
substandard housing. These social factors, emotional instability, and inadequate
mothering result in a harsh, nonnurturing environment. The children frequently are
temperamental and difficult to care for. They are either intensely irritable or
immobile and unresponsive. Their behavior affects that of their caretakers.
Two current hypotheses have been proposed to explain the changes in weight and
length. Some clinicians5 have presented evidence that undereating is the main
etiologic factor; this theory is supported by the prompt gain in weight which frequently follows the removal of the child from the home. However, a
neuroendocrine derangement secondary to emotional deprivation has been another
hypothesis. No study has attempted to establish the relative roles played by the two
factors. The developmental and multidisciplinary nature of the problem makes it a
difficult research endeavor.
The child suspected of failure to thrive should be hospitalized
Protein-calorie Malnutrition for observation in a controlled environment.
Usually no organic disease is present. However, this cannot be taken for granted,
and appropriate studies should be performed. In some instances 4 the syndrome is
superimposed on another disease process. Because of the secondary malnutrition,
studies of intestinal absorption should be delayed until after 10 to 14 days of
feeding, when many of the gastrointestinal symptoms will have disappeared. There
is a fine line between failure to thrive and child abuse.
Treatment of the infant or child with failure to thrive usually is a slow process.
Adequate nourishment and a loving and supportive environment are necessary.
6. Prognosis: is excellent with early treatment.
PHENYLCETONURIA.
Phenylketonuria (PKU), one of the best understood genetic disorders and the first
to be screened for in Hawaii (1966) (10), results from phenylalanine hydroxylase
(PAH) deficiency. The enzyme deficiency leads to build-up of phenylalanine that
is toxic in high levels to brain growth and nerve myelination. This causes mental
retardation, abnormal behaviors and skin rashes. In addition, the PAH enzyme is
necessary to convert phenylalanine to tyrosine which is required for melanin
synthesis. With a defective enzyme, the individual is unable to produce proper
levels of tyrosine which results in poor pigmentation of skin and hair (10,12).
1.Etiology a deficiency of the enzyme phenylalanine hydroxylase prevents
conversion of phenylalanine to tyrosine with buildup of the toxic metabolites
phenylacetic acid. The metabolite phenylpyruvic acid ( a breakdown produkt of
phenylalanine) spills into the urine to give the disorder the name. This causes urine
to have a typical musty or “mouse” odor. This is a very strong odor that often
pervades not only the urine but the entire child. Tyrosine is necessary for building
body pigment and thyroxine. Without it, body pigment fades and the child
becomes very fair skinned, blonde and blue eyes.The child have poor growth
standards owing to the luck of thyroxine production. Mane children develop an
accompanying seizure disorder. The skin is prone to ekzema ( atopic dermatitis).
2. Clinical features: develops after 6 month of life, hypopigmentation (white
skin, blue eyes), emotional indifference, cramps, mental retardation, neurologic
manifestations, including hypertonicity and tremor, unusual odor of urine ( like
mouse )
3. Diagnosis: Phelling’s test, microbiologic tests, biochemical tests.
4. Therapeutic management: Early identification of the disorder is essential to
the prevention of menthal retardation. Infants must be screen close to birth.
Infants in whome this disease is detected in the first few days of life can be plased
on an extremely low phenylalanune formula. If the diet prescribed so early,
mental retardation can be prevented. A dietitian may reccomended a small
amount of milk in the infants diet every day so that the child does receive some
phenylalanine because this essential aminoacid is necessary for growth and repair
body cells. Preparing the diet for child with PKU is a difficult task. There is no
natural proteine with both a low phenylalanine concentration and a normal
concentration of other essential amino acids. A diet of just protein restriction
therefore, would result in restriction of all essential amino acids. Fods highest in
phenylalanine are all protein-rich foods: meat, eggs, milk. Low phenylalanine
foods include juice, bananas, potatoes, lettuce, spinach, peas.
4. Prevention : restriction of dietary intake of phenylalanine ( milk, meat, eggs ).
CELIAC DISEASE
DEFINITION:
A malabsorptive disorder characterized by a permanent gluten-sensitive
enteropathy resulting in malabsorption, failure to thrive, and gastrointestinal
manifestations.
EPIDEMIOLOGY:
 incidence: 20/100,000 (declining with peak in early 70's);prevalence: 1/5003000 ; age of onset: usually develops before age 2 ; risk factors:
 food - BROW (barley, rye, oats, wheat)
 sex - F > M (1.3-2.8:1) ;geographic : Western Ireland, Europe .
 diet - decreased duration of breast feeding
 early introduction of gluten into diet
 immunologic HLA types:
 Class I antigen - HLA-B8 (60-90%)
 " II " - " -DQw2 (80-100%)
 " -DR3 or DR7 (70-80%)
 infection with adenovirus type 12 (homology between viral peptide and
gliadin peptide)
 genetic
 monozygotic twins - 70% concordance
 first degree relatives:
 10% prevalence rate of occult celiac disease
 2-5% risk of developing overt "
1.Etiology a deficiency of the enzyme gliadinamynopeptidas e resulting in
malapsorbtion of cereal proteins ( gliadine and avenine ).
PATHOGENESIS:Gluten is the major form of stored protein in wheat and gliadin is
a glycoprotein extract from gluten and this latter component is toxic to the small
bowel mucosa of those with celiac disease. The pathophysiology of gliadininduced damage to the mucosa is unknown but there are at least three hypotheses:
1. Toxic: catablism of gliadin may produce a metabolite which causes direct
injury to the enterocytes ; excess gliadin directly binds to an abnormal receptor
on the surface membrane of the enterocyte -> injury - an abnormal
immunologic response to gliadin ;Mild cases involve the proximal small bowel
with distal spread to the whole small bowel in more severe cases. As the lesion
is con-tinuous and not patchy, to make the diagnosis only the proximal small
bowel needs to be biopsied. When a gluten-free diet is initiated, the mucosal
recovery progresses proximally so that the upper small bowel recovers last.
CLINICAL FEATURES: develops after initiation of proteins – containing feeding (
cereals, bread ), in about 5-6 month of life, diarrhea, stools with bad
odor in a big quantity,enlarged abdomen, thin arms and legs, anemia,
edema, pseudoascites.
1. Gastrointestinal Manifestations







failure to thrive
diarrhea - chronic or recurrent, occasionally fulminant
flatulence +/- abdominal pain or vomiting
malabsorption signs and symptoms:
protein
fat
others - vit. B12, iron
2. Musculoskeletal Manifestations
 wasting: limbs & buttock with marked abdominal distension
3. Others
 anasarca, anemia, apathetic, delayed puberty, hypotonic, irritable, mouth
sores, pale, peripheral edema, rectal prolapse, smooth tongue, clubbing,
dental enamal hypoplasia
INVESTIGATIONS:
1. For Malabsorption
2. Imaging Studies
 upper GI may show intestinal dilatation and thickening of the mucosal folds
3. Biopsy
1. Duodenum or Jejunum











crypts - hyperplastic & elongated with decreased life span
villi - atrophy (total or subtotal) -> flat & blunted
mucous membrane inflammation
lymphocytic infiltration of the epithelium by cyto-toxic/suppressor T cells
plasma cell infiltration of the lamina propria
morphologic changes in surface enterocytes
columnar -> cuboidal or flattened
increased RNA content -> basophillic cytoplasm
nuclear disarray
poorly defined brush border
decreased enzyme activity (i.e., disaccharidases)
4. Serum Screening
 CBC, ferritin, folic acid
 decreased albumin, calcium, magnesium, and iron
DIAGNOSIS:
1. Gluten Challenge
 first advocated in 1970
 3 biopsies: 1st - typical histologic findings on gluten diet ; 2nd - full
recovery of the mucosa on gluten-free diet ; at 2-3 months after start of
gluten-free diet ; 3rd - histologic relapse on gluten diet; changes detectable
within 2 months .
2. Screening Tests. 1. Absorption/Permeability Tests : D-xylose absorption
test , Urinary lactulose-to-mannitol ratio.
2. Serum Antibodies: antigliadin IgG and IgA; antireticulin " ;
antiendomysial IgA - connective tissue component .
MANAGEMENT:
1. Dietary Management restriction of dietary intake of gliadine-containing food.
(weat cereals, bread), taking ferments and vitamines.
1. Avoid wheat, barley, rye, and oats , processed foods (wheat flour).
2. Prefer rice, soya, corn flours, unprocessed foods.
2. Follow-up growth curves (declining weight and height are the most consistent features of Celiac) , nutritional deficiencies .

long-term complications: esophageal carcinoma , small bowel
adenocarcinoma , small bowel lymphoma .
3. Natural History : exacerbations and remissions, long-term prognosis is
excellent
in the blood.
gland). Over time, there is an accumulation of galactose-1-phosphate which manifests as
vomiting, lethargy, diarrhea, cataracts, developmental delay and mental retardation, liver and
kidney disease. In galactosemia, there is an increased likelihood of sepsis from gram negative
organisms that may cause death in the neonatal period .
MARFAN SYNDROME
1.Etiology is production of abnormal fibrillin ( major protein of the myofibrills )
which result to connective tissue abnormalities.
2.Clinical features: Skin lesions, Skeletal manifestations:
a) unusually long, thin digits ( arachnodactyly) and limbs, disproportionate tall
stature.
b) Scoliosis and chest deformity ( pectus carinatum );
c) Hypermobile joints;
d) Long thin face with a high, narrow palate;
II Ocular manifestations :
a) Myopia ( may be very severe )
b) Lens subluxation may occur.
III.Cardiovascular manifestations:
a) Dilatation of the aortic root; mitral valve prolapse;
IV. Pulmonary manifestations:
a) Spontaneous pneumothorax;
b) Emphysema.
3. Diagnosis: to make the diagnosis, at least two major manifestations must be
present:
1. Skeletal manifestations;
2. Ocular manifestations;
3. Cardiovascular manifestations;
4. Pulmonary manifestations;
5. Positive family history.
Students Independent Study Programme.
I. Objectives for Students independent study. Great attention should be paid to
the following items:
1. Ethyology and pathogenesis malnutrition.
2. Classification of malnutrition.
3. Main clinical features of malnutrition.
4. Clinic diagnosis and laboratory examination of children with malnutrition .
5. Main principles of treatment.
II. Tests and Tasks for Independent Study.
Select the right statements:
1. Clinical features of malnutrition include all of the following, EXCEPT:
a) skin and mucus membranes are dry
b) turgor of skin is increased,
c) muscular hypotonia,
d) patients have asthenic constitution ;
e) children has intellectual defects
f) they has weight and length deficiency.
2. What laboratory and instrumental investigations helps in the diagnosis
of malnutrition :
a) Culture of stool;
b) Chest X-ray
c) Biochemical examination of the blood
d) Immunological tests
e) General examination of the blood,
3. What symptoms helps us to put the diagnosis of SEVERE FORM of
hypotrophya in the patients?
a) bradycardia,
b) dryiness of the skin and mucus membranes,
c) hypoglycemia
d) weight loss on 30 % and more
e) decreasing body temperature
Problem situations to be solved:
7. 1-month old child has a persistent diarrhea, skin is pale, regurgitation, periodic
vomiting, bad appetite, was born from II physiological pregnancy in term 39 week
with the weight 2.500 gr, length 47 sm. Patient have reduced degree of
nourishment, weight loss ( at the present time his weight is 2.800 gr), the abdomen
is great, distended, meteorism, the skin and mucus membranes are dry, turgor of
skin is decreased, muscular hypotonia Subcutaneous fat is absent on the abdomen,
legs and arms. The examination of the blood shows hyponatremia,
hypoalbuminemia ; Put your diagnosis
III. Test and Task Keys for Self-Assessment Study.
Tests: 1-b,e; 2-a,c,d,e; 3-a,c,d,e . Problem situation: Prenatal malnutrition of the III
stage.
Illustrative Material. Tables:
Test Tubes:
Student's Practical Activities.
Student's will be able to know:
A) Diagnostic criteria of malnutrition;
B) Main clinical features of malnutrition;
C) Diagnosis and diferential diagnosis of malnutrition;
D) Principles of treatment of malnutrition.
Student's will be able to do:
A) To take the patient's history;
B) To take the patient's complaints;
C) To find clinical symptoms, special for malnutrition;
D) To write the clinical diagnosis;
E) To manage the treatment of malnutrition in depending of the age of the child
and severity of disease.
Information Sources:
A)
Pediatrics ( 2nd edition, editor - Paul H.Dworkin, M.D.) - 1992. - 550 pp.
Prepared by: Nykytyuk Svitlana
Adopted in the Chair Sitting. Minutes N .....................