V. APPENDIX5.1. Lectures

5.1.1. Anomalies of Constitution

We speak about constitution’s anomalies when organism’s functions are in a state of un-steady equilibrium; when an organism has some individual congenital, hereditary and sometimes acquired constant characteristics, which predispose it to pathologic reactions at external harmful-ness, make it incline to proper diseases and to their severe course (M.S. Maslov).

The term “diathesis” corresponds to the notion “predisposition”, that is narrower than no-tion “constitution’s anomaly” and is determined by Veltischev Yu.E. as polygenically heritable susceptibility to diseases, objectively recognizable deviations from normal phenotype.

Four diatheses are described in pediatrics from 20th years of the 20th century: exudative–catarrhal, lymphatic-hypoplastic, neuroarthritic and allergic. First three of them are anomalies of constitution and we use the term “diathesis” conditionally, having in mind that these diathesis are specific dysfunctions of maturation, overstrain in proper systems. Expediency of marking out of indicated constitution’s anomalies in separate diagnosis is determined by a consideration that they designate concrete conditions in infants, which demand peculiar approach to organization of diet, regimen, vaccinations, treatment of diseases appeared on the ground of diathesis.

EXUDATIVE – CATARRHAL DIATHESISThe notion “exudative diathesis” (ED) was used for the first time by A. Cherny in 1905,

and means peculiar state of reactivity in infants, which is characterized with susceptibility to re-current infiltrative, desquamate skin and mucous membranes lesions, to development of allergic reactions and prolonged course of inflammative processes, to lymphoid hyperplasia, lability of water-salt metabolism.

Transitory signs of ED and/or infantile eczema are marked in 40-60% of infants during first two years of life.

Etiology. The great majority of pediatricians consider allergy to play the main role in eti-ology and pathogenesis of ED. At the same time ED may be only an episode in infant’s life; al-lergic diseases will develop later only in 25% of children.

Infants have decreased barrier intestine function because of lack of enzymes’ activity for complete proteolysis, hyperpermeability of intestine’s wall, decreased synthesis activity of secre-tory IgA.

The majority of children have non-immune (allergoid) genesis of ED, that is pathochemi-cal and pathophysiological phases of allergic reaction of immediate type develop without first immunologic phase. On the one hand it may be stipulated by excessive secretion and liberation of histamine from mast cells (liberatory variant), on the other hand – by its insufficient inactiva-tion (hystaminaze variant).

Peptons, proteolytic enzymes, toxins and poisons, monoamines and other substances may be histamine liberators (except complex antigen-antibody). Besides intestine’s hyperpermeability for proteins there is low stability of mitochondrial and lysosomal membranes in infants, and be-cause of it – great quantity of proteolytic enzymes in blood.

Insufficient inactivation of biogenic amines in infant’s blood is stipulated by low activity of histaminaze and ability to histaminopexia, and by decreasing activity of carboxypolypepti-dase, monoaminooxidase, and acetylholinesterase.

Tissue’ sensitivity of infants to histamine is higher than in children of school age, and liberation of great quantities of histamine from mast cells may occur due to meteorological fac-

168

tors (e.g. supercooling), vitamin deficiency, different diseases (e.g. ARI, intestinal infections, dysbacteriosis).

Factors, which provoke clinical manifestations of ED are the following: proteins of cow milk (especially in overloading – more then 3 g/kg/day), eggs, citric plants, wild and garden strawberries. It is necessary to underline that eggs, wild and garden strawberries, lemons, ba-nanas, chocolate, fish contain liberators of endogenic histamine (without participation of rea-gins). In infants receiving breast-feeding diathesis may appear because their mothers could eat these food products.

Pathogenesis. Principal difference of infants with ED from infants with atopic diathesis is food dose–dependence of ED manifestations. Only great quantity of food eaten by mother or by infant may provoke allergic reaction. In atopic diathesis even minimal quantities of allergen lead to severe generalized allergic reaction.

Infants with ED have hydrolability – on the one hand, susceptibility to retention of water, sodium, and due to it – excessive weight gain, friability, on the other hand – quick dehydration with great weight loss in a course of intercurrent diseases. Other metabolic peculiarities of in-fants with ED: metabolic acidosis, activation of free-radical peroxide lipid oxidation, tendency to hypoproteinemia, hyperglycemia, hyperlipidemia because of liver function disorder, suscepti-bility to hypovitaminosis, Fe-deficient anemia, deficiency of microelements. Because of de-creased activity of some digestive glands infants with ED have instable stool, and because of pe-culiarities of immunologic reactivity they have increased lymph nodes, intestine dysbacteriosis.

There is common pathogenetic link of ED and atopic diathesis – intrauterine sensibiliza-tion because of nutritional defects in pregnant women. They do not only abuse food obligatory allergens (honey, chocolate, nuts, eggs, cheese, fish, wild and garden strawberries etc.), but there was excess of animal protein and lack of vegetables in their diet.

Clinic. Persistent intertrigo in skin folds from the first month of life, xerodermia and skin pallor, and adipose seborrhea sales on the scalp (“potato chips”) are revealed. Characteristical symptoms of ED: milk crust (temperature depending cheek’s reddening and peeling), wrong weight gain (more often excessive weight gain, but may be steep curve of mass accumulation and prolonged – of its assimilation, that is delay of weight gain), skin eruptions (erythema-tovesicular, erythematopapular), strophulus (itching nodes with serous contents), “geographical tongue”, prolonged conjunctivitis, rhinites, catarrh of respiratory tract with obstructive syn-drome, anemia, elevated content of epithelial cells in urine, unstable stool.

The course of ED is undulating; at the end of the second year its manifestations alleviate and disappear, but in 25-30% of children eczema, neurodermitis, bronchial asthma and other al-lergic diseases may develop.

Diagnosis. Diagnosis usually is not difficult; it’s necessary to differentiate it from infan-tile eczema and other skin diseases.

We can speak about true eczema when allergic essence of disease is clear, hereditary ag-gravation as for allergy exists, not only overloading with cow milk leads to appearance of skin lesions but even its minimal quantity has the same result.

Treatment. Rational feeding. Infant with ED has to receive proteins, fats and carbohy-drates with accordance to age norm and type of feeding. It is useful to restrict caloric value ow-ing to easily assimilated carbohydrates (sugar, porridge, and kissel – kind of starchy jelly). It is expedient to introduce approximately 30% of fat owing to vegetable fats, rich with polyunsatu-rated fat acids. For all of them restriction of salt, additive prescription of potassium salts is rec-ommended. Mother has to exclude obligatory allergens from her diet.

For infants received formula feeding and mixed feeding it is necessary to diminish quan-tity of cow milk; it’s better prepare porridge not with milk but with vegetable water, to give yo-

169

ghurt instead of milk because during souring lactoablumen (the main allergic protein of cow milk) is destroyed.

In some cases of persistent diathesis, especially in demonstrated allergy to cow milk, it’s necessary to feed an infant with milk of almonds or soybean. It is expedient to give additional food for infants with formula feeding at 4-4.5 months, vegetable puree is preferable. For infants with breast-feeding – vice versa – it is recommended to give additional food later than for healthy infants. In many infants ED manifestations alleviate while substitution sugar with fruc-tose in ratio 1.0:0.3. It’s possible to give porridge from 6-6.5 months.

Rational vitaminizaton of food. It is proposed to give vitamin B6 in a dose of 50-75 mg/day. In dry eczema it is useful to prescribe vitamin A 1000 ME/kg during 3 weeks, but not more than 10000 ME/day. In exacerbation of process co-enzymes are evident: cocarboxylase, ri-boflavine mononucleotide, calcium pantothenate (vitamin B5) 100-150 mg/day, calcium panga-mate (vitamin B15) 50-100 mg/day, tocoferol (vitamin E) 25-30 mg/day.

Since in majority of cases allergens enter with food, courses of lactobacterin, bifidum-bacterin, magnesium sulfate have positive influence.

We use 7-10 days courses of antihistaminic drugs. Sometimes it is useful to prescribe aminicapronic acid as antibradikynine remedy. Fitotherapy is recommended as well.

Local therapy of skin lesions is necessary.

ALLERGIC DIATHESIS.The term “allergic diathesis” (AD) was introduced in clinical practice in 20 th years of our

century by Hugoe Kemerer and signify ability to appearance of sensibilization, allergic reactions and diseases because of hereditary, congenital or acquired peculiarities of immunity, metabo-lism, neuro-vegetative system.

Allergic diseases develop in 30% of infants if father has allergic disease, in 50% - if mother has it and in 75% - if allergy is diagnosed in both parents.

I.M.Vorontsoff (1985) proposed to distinguish the following variants of AD: atopic, au-toimmune, and infectious-allergic.

Atopic diathesis : positive family allergic history, laboratory data – increased quantity of IgE in blood serum, decreased indices of histaminopexia, decreased level of noradrenalin in blood serum, diminution of glycemia to adrenaline, enforcement of spontaneous histamine liber-ation from leukocytes; results of functional tests – white dermographism, sharp rise of skin sen-sitiveness to intradermal injection of histamine with elevation of skin temperature.

Autoimmune diathesis : elevated skin sensitiveness to UV-irradiation, marked rise of gamma-globulin in blood, not rare exposure of LE-cells, antinuclear factors in a condition of full well-being.

Infectious-allergic diathesis : prolonged periods of elevated ESR and subfebrile tempera-ture after ARI, appearance in their course such symptoms as cardialgia and arthralgia. Suscepti-bility to vasculitis is observed.

There is association with HLA: in AD – B8, B18, B16; in autoimmune diathesis – B8, DRw3, DR3, SCO1, Cw7; in infectious-allergic diathesis – B12, DRw6, DRw4.

In change of AD to allergic disease, besides contact with allergen, the following causes play a role: existence of local foci of infection in respiratory tract and intestine; thermal, chemi-cal, physical skin irritation, insufficiency of detoxic liver function, appearing after its infectious lesion, hypovitamonoses, not rational feeding, dysbacteriosis.

Clinical picture has not typical constitutional features, although these infants are more often hyperstenics. At the first year of life there are signs of ED, rarely – of lymphohypoplastic or neuro-arthritic diatheses. These are the infants with nerve hyperexcitability and irritability, sleep disorders, decreased appetite, capricious. As a rule they have enlarged liver, signs of dyski-

170

nesia of biliary tract or cholecystitis, dysbacteriosis (constipation or unstable stool, abdomen pains, meteorism, “geographical tongue”). Foci of chronical infection, increased lymph nodes and spleen, prolonged periods of subfebrile temperature, lingering course of infectious diseases, especially respiratory infections with obstructive syndrome, are often. They don’t tolerate inten-sive physical load (attacks of pain, collapses, etc.).

AD at the first year of life more often changes to skin lesions, at the under school age – to respiratory allergoses, including bronchial asthma, in school years - to eczema, neurodermitis, dermorespiratory allergosis.

Diagnosis. History data lay in a basis of diagnostic. In a great majority of cases there are relatives, more often in mother’s brunch, with allergic diseases. It’s necessary to underline that not proper allergic disease is heritable but readiness to allergic reaction, so, nosology of diseases in relatives may be different. Detailed questions about development, feeding, diseases, reactions to vaccination, medical drugs are necessary. Names of drugs and food products must be written down on the cover of case history and underlined with red pencil.

Prevention must be complex with its beginning in antenatal period. In polyclinics it is necessary:

-to keep food diary;-maximally prolonged breast-feeding with relatively late intake of juices (from 3 months)

and additional food (from 6-7 months). Juices and additional food with high sensibilizing activ-ity must be excluded from infant’s feeding, especially juices from red and yellow fruits. In mixed and formula feeding it’s expedient to use sour milk products, 1-2 times per year to pre-vent dysbacteriosis with bifidumbacterin;

-after 1 year the diet is prescribed without obligatory allergens, extractive substances (broth, flavoring, spices, canned food, and piquant and salt dishes);

-creation of hypoallergenic conditions at home: humid tidying twice a day, including ra-diators, floor under the beds, tops of wardrobes; domestic animals, fishes in aquarium, flowers are undesirable; the floor must be covered with linoleum or varnish; carpets, books in unclosed shelves, washing with synthetic washing soda in the child’s presence, downy and feather pil-lows, mattresses and blankets are intolerable;

-individualization of vaccination plan and preparing of infant to vaccination with non-specific hyposensibilising therapy;

-excluding of obligatory allergenic remedies (penicillin, biologic drugs) and use of mini-mum drugs in diseases;

-early exposure and active treatment of foci of chronic infection, dyskinesia of biliary tract, anemia, rickets, helmintoses, hypotrophia, dysbacteriosis.

Vaccination is possible only in 6 months after last exacerbation of allergosis.

LYMPHOHYPOPLASTIC DIATHESIS (LHD)The term “lymphohypoplastic diathesis” was used for the first time by Austrian patholo-

gist A.Paltauff and pediatrician T.Esherich in 1889-1890 y.y.Lymphatic diathesis – constitutional anomaly which is characterized by the generalized

constant increase of lymph nodes even in the absence of infections, dysfunction of endocrine system (dysfunction of adrenal gland and sympathico-adrenal system, dysplasia of thymus) with decreased adaptation to influences of surroundings, susceptibility to allergic reactions.

Since such children have hypoplasia of chromaffine tissue, reticuloepithelial apparatus of thymus – Hassal’s corpuscles (with simultaneous hyperplasia of reticular stroma of lymph nodes), sexual glands, cardio-vascular apparatus, non-striated muscles, it is more correct to speak about lymphohypoplastic diathesis. It occurs in 3.2 – 6.8% of children under school age.

171

Etiology. Factors of surroundings, acting both in intrauterine (gestoses of pregnant women, mother’s diseases leading to increased placental permeability and passive fetal sensibi-lization, mother’s infectious diseases of the second half of pregnancy) and in extrauterine period (prolonged infectious-toxic diseases, unrational feeding with excess of proteins or carbohydrates etc.) play the main role in forming of LHD.

LHD occurs more often in children from families with allergic predisposition that brings together its pathogenesis with pathogenesis of ED. It is difficult to differentiate these conditions clearly; on one hand, children with ED often have signs of “lymphatism”, on another hand – children with LHD (approximately 1/3 part) have exudative-catarrhal skin lesions. Probably, prolonged toxico-infectious diseases play the main role in formation of LHD while allergic fac-tors of surroundings – in formation of ED. Under influence of prolonged infectious-toxic factors on the ground of allergic predisposition function both of peripheral and central (thymus) lymph apparatus gets broken that leads to renal gland and chromaffine system dysfunction.

Pathogenesis. There is interaction between thymus and renal glands like inverse link. Probably, substances which are synthesized by reticuloepithelial apparatus of thymus, suppress glucocorticoid secretion, while hormones which are synthesized by lymphoid apparatus, stimu-late it. Maybe, correlative interaction of thymus and adrenal gland realized on the level of hypo-thalamus, as on the one hand, hormones stimulating secretion of renal glands’ hormones and on the other hand – substances influencing thymus function, were isolated from it, and level of ACTH in LHD has a tendency to decrease.

It has been proved that intensity of synthesis of catecholamines and glucocorticoids in children with LHD is decreased, and on this ground ratio of synthesis of glucocorticoids-miner-alocorticoids is moved to the side of mineralocorticoids, that favored the secondary hyperplasia of lymphoid tissue, retention of sodium, water and chlorides in organism. Water metabolism in such children is unstable. It stipulates great variations of body weight, easy development of edema. Blood sugar level is not high as a rule.

Besides lymphocytosis low level of thymic factor in blood serum is seen, as well as ele-vated quantity of B-lymphocytes and T-suppressors and diminution of total quantity of T-lym-phocytes and T-helpers (ratio of T-helpers/T-suppressors which makes 2.0 in norm decreased to 1.0 and less).

Clinic. Children with LHD are pale, flabby, apathetic, they have excessive body weight; tissue’s turgor is decreased, skin fold is flaccid, muscles are badly developed, their tonus is de-creased. Height corresponds to the age norm or exceeds it owing to more long extremities. Short neck, wide bones but at the same time not long narrow scapulas, narrowing of upper thorax aperture, horizontal position of ribs, genu valga, pedes plani (flat, splay foot). The children quickly get tired, badly tolerate long and strong irritations.

Susceptibility to constant increase of peripheral lymph nodes and thymus is the most typ-ical feature as well as increase of mesenteric, mediastinal lymph nodes, lymphatic folliculi of posterior wall of pharynx, tongue, palatine and pharyngeal tonsils. Adenoid vegetations lead to disorders of nasal respiration, rhinitis, peculiar adenoidal type of face, deteriorate brain blood flow.

Skin lesions revealed in ED not rare occur in infants with LHD, but they are not consid-erable, though respiratory allergoses are typical for them.

These children have susceptibility to slight appearance and severe long course of inflam-matory diseases of upper respiratory tract with development of neurotoxicosis, disorders of mi-crocirculation. Sometimes there is small, so called “drop heart”, sometimes – heart enlargement, functional systolic murmur on the apex, more rarely – hypoplasia of aortic arch, congenital heart disease.

172

Maximal manifestations of LHD develop usually at 3-6 years, later they smooth over or disappear, though retardation of sexual maturation may be seen.

Diagnosis and differential diagnosis. It is necessary to remember that increased thymus in thorough clinico-radiological investigation may present in 30-50% of infants, oftener after diseases. This is a physiological condition. Besides this, there is some hyperplasia of peripheral lymphoid apparatus in children of 3-6 years old. Its cause isn’t clear. It is possible to diagnose LHD when there is typical outward appearance in combination with constant significant increase of thymus and lymph nodes, preserved even in period free from infections. It’s expedient to prove decrease of renal gland function by laboratory methods.

Rise of cardio-thymico-thoracic index (ratio of cardio-thymic width in a place of tracheal bifurcation to transversal thoracic diameter at the level of diafragmal cupola expressed in %) in first 6 months of life - >50%, 6-12 months - > 43%, elder 1 year - >38%, 3-6 years - 35 %, 7 years and more - >27% is a rentgenologic sign of thymus enlargement.

It’s necessary to exclude hereditary immune deficiency, diseases which lead to general-ized enlargement of lymph nodes.

Treatment. Maintenance of day regimen, enough stay at plain air, planned hardiness, massage and gymnastics play main role in the treatment.

It is expedient to restrict cow milk and easily assimilated carbohydrates in infant’s feed-ing. It is better to change fresh milk to sour one, to give vegetable and fruit additional food. Pre-scription of adaptogens, stimulating defensive forces of organism and adrenal glands function is useful (ginseng, dibasol, metacil, pentoxil, vitamin B5, B6, B12, A, E, potassium orotate), besides, it is necessary to diagnose and treat rickets, anemia, concomitant infections.

It is necessary to resect adenoid vegetation only in complete absence of nasal respiration or in often recurrent inflammations of respiratory tract organs. Not rarely they may appear again after adenoidectomy.

Prevention. Treatment of infections, transmitted by sexual way (>20), rational diet of pregnant women and infant’s feeding in accordance to age, maintenance of day regimen, stay at plain air, hardiness, massage and gymnastics has an important value.

NEUROARTHRITIC DIATHESIS (NAD).The term “neuro-arthritic diathesis” was introduced to pediatrics by D.Kombi in 1901-

1902 y.y.NAD is characterized by nerve hyperexcitability, nutritional disorders, susceptibility to

ketoacidosis, and more later – to obesity, interstitial nephritis, nephrocalcinosis, gout and meta-bolic arthritis, that is stipulated by purine metabolism’s disorders.

Etiology. On the one hand, inheritance of some pathologic characteristics of metabolism, and on the other hand – diet, regimen, surroundings play a role in formation of NAD. In a fam-ily of infant with NAD it is revealed, as a rule on father’s branch, such diseases as gout, obesity, hemicrania, neuralgia, nephrocalcinosis.

Pathogenesis. The following disturbances have the main value in NAD pathogenesis:1) high level of excitability at any level of reception;2) purine metabolism’s disorders with their elevated concentration in blood and urine;3) low acetylizing liver ability.

The most typical laboratory test in this diathesis is elevated level of uric acid in blood (>268 mcmol/l). Increase of uric acid synthesis, not decrease of its dissociation, is seen.

Susceptibility to allergic diseases in NAD may be explained with the fact that uric acid inhibits synthesis of cyclic nucleotides, adenilatcyclase. Decrease of glucose blood level, lypoly-sis in starvation (vomit, long intervals between food intake), acute diseases, stresses, and excess

173

quantities of fat in food stipulate ketogenesis and development of ketoacidosis up to coma. But to 9-11 years acetonemic attacks cease.

Clinic. Already in infants nerve hyperexcitability may be seen. Elder children become even more excitable, for example, may cry because of mosquito bites. Psychical development of children with NAD pass ahead of norm: they are inquisitive, vivid, easily keep in mind poems. They are often said to be infant prodigy. They have strong unbalanced hyperexcitable type of nerve system. Not rare they have night fears, tics, and chorea like attacks, steady resistant anorexia. The great majority of children with NAD are thin, but some of them are stout. Some-times, more often the girls quickly gain weight in pubertal age. The smell of acetone from the mouth may be in the morning. Stool as a rule is abundant nevertheless decreased appetite.

Periodically repeated indomitable vomit lasting 1-2 days, fit like abdomen pains, acetone smell from mouth may appear all of a sudden or after short indisposition (excitement, headache, anorexia, nausea, constipation, acholic stool). Later exicosis, toxic breathing, hemodynamic dis-orders, hyperthermia and coma may develop. This condition is named acetonemic vomit (crisis). Acute diseases, stresses, abuse of meat and fatty food with insufficient quantity of carbohy-drates, feeding under compulsion may provoke this state.

Children with NAD may have causeless rise of temperature, hemicrania attacks, urtic and papulous eruptions after mosquito bites, edema of Quincke, nettle rash, asthmatic bronchitis, and bronchial asthma. Uricosuric nephropathy is characterized with proteinuria, microhematuria, leukocyturia, cilindruria, interstitial nephritis with decrease of concentrative renal ability, sus-ceptibility to hypertension, pyelonephritis, urolithiasis. These children have infectious processes with the same frequency as other children. Typical gout attacks at the infantile age are absent, though many children complain of periodical transitory joint pains.

Differential diagnosis. It is necessary to differentiate NAD from neuroses, rheumatic fever, infect arthritis, pyelonephritis, and subfebrile conditions because of chronic infection foci, chronic pancreatitis and cholecystitis. Hereditary anomaly of purine metabolism – syndrome of Lesh-Nihan – is known.

Treatment. The main method of treatment is rational regimen and diet. It is necessary to protect the children from intensive physical load, limit reviews of TV-programs. Systemic hardi-ness, physical exercises in the morning, walks are of great use.

Milk products, vegetables, fruits must prevail in diet. Meat, paultry, fish (especially fried, smoked), broth, fats (except vegetable), sugar, confectionery are limited. Products rich in purine base and coffein (liver, brain, kidneys, herring, pate, sardine, chocolate, cacao, coffee) are ex-cluded from diet. It is of no use to feed children under compulsion, but it’s necessary to avoid long intervals between food intakes. At night it is better to give hardly assimilated carbohydrates (porridge, buckwheat porridge, potato, vegetables, and rye-bread). In bad appetite it is useful to prescribe abomine, gastric juice, and vitamin B1, B6, potassium orotate.

In initial symptoms of acetonemic attack it is expedient to give glucose solution, sweat tea, fresh fruit juices, melon, watermelon, alkaline mineral water or 0.5-1% solution of sodium bicarbonate every 10-15 minutes. Food with easily assimilated carbohydrates and minimal quan-tities of fat (milk, sour milk, potato or vegetable puree) are indicated. Cleansing enema is neces-sary. Essentiale forte (1-2 capsules/day during 1-2 weeks) or vitamin B12 (100-300 micrograms every second day i.m.) is prescribed. In severe attacks of acetonemic vomit it is necessary to in-ject i.v. by drops 5-10% solution of glucose in two with 0.9% solution of sodium chloride, co-carboxylase, ascorbinic acid, if pH < 7.2 – 4% solution of sodium hydrocarbonate. Cleansing en-ema and gastric lavage are necessary.

Pathogenetically repeated courses of vitamin B5 (100-150 mg/day), potassium orotate (50-100 mg/day), allopurinol (10 mg/kg/day) with uricosuric remedies (ethamid, atophan, citric mixture) and hepatotrophic remedies (LIV-52, essentiale, etc.) are indicated.

174

Prevention. Maintenance of day regimen, rational diet, protection against excessive physical and psychical loads.

5.1.2. Chronic disorders of nutrition (CDN)CDN are seen predominantly in infants and may be of 2 types: adiposity and malnutrition

(hypotrophy).The main, most often variant of hypotrophy is protein energy malnutrition (PEM). As a

rule, there are hypovitaminoses and sometimes trace elements deficiency in such children.Protein energy malnutrition (PEM)Undernutrition is widely recognized as a major health problem in the developing coun-

tries of the world. The frequency of undernutrition cannot be easily estimated from the preva-lence of commonly recognized clinical syndromes of malnutrition such as marasmus and kwash-iorkor because these constitute only proverbial tip of the iceberg. Cases with mild to moderate undernutrition are likely to remain unrecognized because clinical criteria for their diagnosis are imprecise and difficult to interpret accurately.

Undernutrition is often diagnosed by comparing the weight, height and mid-arm circum-ference of an individual with the anthropometrical norms for the corresponding age in that com-munity. Reliable anthropometry is not easily available in most developing counties. It is difficult to define “what constitutes an appropriate and optimum body size”. Children who receive less food do remain small. The prevalence of undernutrition cannot be judged solely from an estima-tion of the quantity of food consumed by an individual in the recent past. Human body has a re-markable capacity to adjust its metabolism to meet some variations in the daily intake of food. Unless nutritional deprivation is severe and prolonged, short-term deficit may not produce any significant physiological disturbance.

By data of WHO there are 20-30% of infants in developing countries who have PEM and other variants of undernutrition.

Causes of undernutritionInability to pay for food.The most common cause of malnutrition is poverty. The poor cannot purchase adequate

amount of food of the desired quality for meeting their and their family nutritional requirements. This deprivation adversely affects their capacity for physical work and endurance. They earn less and these starts a vicious cycle of poverty – undernutrition – diminished work capacity – low earning and poverty. In the new social milieu, competing demands for non-food expendi-ture, such as, on housing, clothing and entertainment have gone up significantly often at the cost of the expenditure on food.

Feeding habits.Exclusive breast-feeding gives a nutritional advantage to the babies during the first few

months of life. If the lactation fails or if the breast milk supply is not sufficient to satisfy the nu -tritional needs of the infant, artificial feeding is employed. In most rural household weaning is delayed, often beyond one year. Diluted cow or buffalo’s milk in small quantities supplements breast feeds. Solid energy dense and protein rich foods are started late. Enteric infections espe-cially diarrhea is not unusual during the weaning period. The weaning diarrhea is wrongly attrib-uted to teething by parents, who often withhold food supplements or dilute the milk still further during episodes of diarrhea. Prevailing dietary practices and cultural taboos on consumption of certain types of foods are the other conditioning factors leading to malnutrition.

Advertising of baby foods high pressure.

175

High pressure of advertising by baby food manufacturers and social demands on the ur-ban educated working women has encouraged early discontinuation of breast-feeding. Unfortu-nately evaporated dry milk powders and packaged foods are expensive. Poor mother tends to economize on their use and offers diluted milk formula to the infant. Unhygienic feeding prac-tices on the preparation of milk formula result on frequent episodes of diarrhea and diminished absorption of food by the infant.

InfectionsInfections such as malaria and measles precipitate acute malnutrition and aggravate the

existing nutritional deficit. Recurrent attacks of diarrhea on preschool children are a major con-tributory factor in etiology. During infections, child’s appetite is impaired. There may be iatro-genic restriction of food by the parents. The patient catabolizes his own tissues to produce the additional heat energy, which is lost during fever. Therefore such infants lose weight. Metabolic demands for protein during infections are higher. Protein is lost because of tissue breakdown and in pus and exudates. Malnutrition may adversely affect the immune status and make the mal-nourished individuals more vulnerable to infections. This sets up a vicious cycle of malnutrition – infection – malnutrition.

EtiologyThe causes of PEM in infants are the following:

1. Alimentary factors – quantitative undernutririon (hypogalactia, administration of insufficient quantity of mixtures) or qualitative undernutrition (insufficiency of proteins, vitamins, trace elements).

2. Infectious factors – intrauterine generalized infections, sepsis, pyelonephritis and urinary tract infections, other foci of infection, which lead to hypovitaminoses, disorders of utiliza-tion of nutritional substances in intestine and tissues. Infectious diseases of gastrointestinal tract leading to prolonged diarrhea, morphologic changes of intestine mucous membrane, in-cluding atrophy of intestinal villi are the most often cause of hypotrophy.

3. Zinc and other trace elements deficiency, hypovitaminoses, toxic factors (ecological, hyper-vitaminosis A or D, drugs poisoning etc.).

4. Anorexia because of perinatal or other brain diseases, unfavorable factors of surroundings, neuroses.

5. Malformations of mouth, gastrointestinal tract such as ileus, pylorostenosis etc.6. Syndrome of “short bowel” after extensive intestinal resections.7. Syndromes of malabsorption (intolerance of lactose, saccharose, glucose, protein of cow or

soya milk; celiac disease, cystic fibrosis of pancreas, exudative enteropathy, enteropathic acrodermatitis, atrophy of villi of small intestine.

8. Hereditary anomalies of metabolism (galactosemia, leucinosis, fructosemia, diseases of Ni-man-Pick, Tey-Saks), immunodeficiencies (predominantly of T-system).

PathogenesisDespite of different causes leading to malnutrition, there is disorder of utilization of nu-

tritional substances (proteins first of all) both in intestine and in tissues. All patients proportion-ally to deficiency of body weight to height have elevated excretion of nitrous substances with urine and disorder of ratio between nitrogen of urea and total nitrogen of urine. This ratio is named ”index of protein nutrition” (IPN). IPN in healthy children, not depending on type of feeding, makes 83-85%; in malnourished infants it is usually decreases (70-35%); in excessive protein feeding – always elevated.

Activity of gastric, intestine, pancreatic enzymes is decreased, as a rule, proportionally to degree of body weight deficit; because of it nutritional load adequate to healthy infant may cause acute disorder of digestion (dyspepsia) in sick one. Intestine in such children is elongated, di-lated, so constipations are typical, as well as dysbacteriosis.

176

Functions of liver (protein-synthetic, antitoxic, carbohydrative, acetylizing etc.), heart, kidneys, lungs are disturbed. Anemia isn’t rare, not only because of protein deficiency, but be-cause of deficiency of zinc, copper, iron, folic acid, piridoxin.

Here there are not disorders of humoral immunity, but disorders of phagocytes activity of neutrophiles and macrophages, depression of T-system with lymphocytopenia (deficit of T-helpers is obvious, so as activity of T-suppressors is normal or slightly decreased) are typical, that lead to frequent infectious processes, which may have latent course.

Hypoproteinemia, hypoalbuminemia, aminoaciduria, plane sugar curves and susceptibil-ity to hypoglycemia, acidosis, hypokalemia, hypokalehystia, hypernatrhystia, retention of sodium, hypocalcemia, hypophosphatemia are typical. Disorders of sodium and potassium me-tabolism are connected probably with activation of renal glands. In mild degrees of hypotrophia there are signs of activation of sympatho-adrenal system that is considered as chronic stress; on the contrary, in severe hypotrophy functional insufficiency of internal glands activity may occur. Hypovolemia is typical for all patients. They are susceptible to cooling.

ClassificationPEM may be classified according to the severity, course and the relative contributions of

energy or protein deficit. Classifications are based on anthropometric measurements, mainly weight and height. Accordingly several classifications are suggested.

Weight for age classification. Gomez’s is an international classification that takes a weight of more than 90% of expected for that age (50th centile) as normal. Weights for age be-tween 76-90%, 61-75% and less than or equal to 60% are classified as grade 1, 2 and 3 malnutri-tion respectively.

Height for age classifications. McLaren classification defines children with less than 80% height of expected for age as dwarf. Those with a height of between 80 to 93% are classified as short and more than 93% of height is seen in normal children. According to Waterlow, children with a height of more than 95% of expected for the age are termed normal. Marginal, moderate and severe malnutrition is labeled when the height is 90-95%, 85-90% and <85% of expected re-spectively for corresponding age.

Weight for age classifications (proposed by Waterlow)Weight for height Height for age Label ≥ 80% ≥ 90%

< 90%NormalStunted

< 80% ≥ 90%< 90%

WastedWasted & Stunted

Protein energy malnutrition can also be classified as being acute or chronic based on an-thropometry. In acute malnutrition weight is primarily affected. A proportionate reduction in weight and height points towards a chronic course. A greater and disproportionate reduction in weight as compared to reduction in height indicates acute or chronic PEM.

Clinical manifestations of protein energy malnutritionClinical manifestations of malnutrition depend on the severity and duration of nutritional

deprivation, the age of the undernourished subject, relative lack of different proximate principles of food and the presence or absence of associated infections. In India and many other developing countries, the major limiting factor in the diet of preschool children is energy. Lack of protein in the diet is more often due to low food intake, rather than a qualitative defect in the diet.

Nutritional marasmus and kwashiorkor are two extreme forms of malnutrition. Patients showing features of both syndromes are said to have marasmic kwashiorkor. Such extreme forms account for a small proportion of cases of malnutrition. A much larger number of subjects

177

suffer mild to moderate nutritional deficit. Patients with mild to severe manifestations of nutri -tional deficiencies, in whom low protein intake in a common denominator but consumption of carbohydrates and fat as sources of energy varies are described as suffering from protein-energy malnutrition.

Mild to moderate undernutrition. If the dietary intake is deficient for a short period, the body adapts its metabolism to compensate the deficit to some extent. Energy and protein in the diet are expended more efficiently and nitrogen excretion in the urine and stools is reduced.

If the food deficit persists for a longer period, the malnourished subject conserves his en-ergy by curtailing physical activity. Moderately malnourished children appear slower and less energetic. If the nutrition deficit continues longer, growth of the child is affected. Growth lag is more pronounced in weight than the length. With prolonged deprivation height is also stunted. Head circumference is not reduced significantly. Chest circumference normally exceeds the head circumference by the age of 1 year, but it may not do so till much later in malnourished children. The weight of the child is reduced and appears disproportionate with long body, thin limbs and unduly large head. Buttocks are flattened with wrinkling of skin over the front of thighs. The scapulae look winged. Abdominal wall is thin and therefore abdomen appears distended. As the nutritional deficit exaggerates with the onset of infections, the child may become marasmic or develop kwashiorkor.

Marasmus. A marasmic subject is markedly emaciated. The body weight is less than 60 percent of the expected one for the age. The fat in the adipose tissues is severely depleted be-cause it is used up for providing energy. The contour of atrophic muscles is evident under the thin and wrinkled skin. Loose folds of skin are prominent over the glutei and the inner side of thigh. The buccal pad of fat is preserved till the malnutrition becomes extreme. A higher propor-tion of saturated fatty acids is stored there and the saturated fat is the last to be depleted. The skin appears dry and inelastic and is prone to be infected. The hair is hypopigmented. The ab-domen is distended due to wasting and hypotonia of abdominal wall muscles. Gaseous disten-sion occurs due to bacterial fermentation of unsplit sugars in the colon. The mid- arm circumfer-ence is reduced. The bony points appear unduly prominent due to emaciation. The baby appears alert, but is often irritable. Marasmic children may show voracious appetite.

Kwashiorkor. Essential features. Markedly retarded growth, psychomotor changes and edema of dependent parts are three essential clinical features of kwashiorkor. The edema starts in the lower extremities and later involves upper limbs and the face. Muscles of the upper limbs are wasted, but the lower extremities appear swollen. The face appears moon-shaped and puffy. The trunk is affected to a lesser extent. In a previously malnourished child edema is precipitated by debilitating illnesses such as measles or diarrhea. With the onset of kwashiorkor, the previ-ously peevish and irritable undernourished child becomes lethargic, listless and apathetic. He takes little interest in the environment and does not play with his toys.

Other usual clinical features.The kwashiorkor patient appears miserable and resents examination by the physician.

Appetite is impaired and it is difficult to feed him orally. The hair is thin, dry, brittle and devoid of their normal sheen. It becomes straight and hypopigmented. The length of the hair that grows during the period of nutritional deprivation appears reddish brown. During the phases of better nutrition, the growing part of the hair gets appropriately pigmented. This gives appearance of al-ternate bands of hypopigmented and normally pigmented hair. These children often suffer from recurrent episodes of diarrhea, respiratory and skin infections.

Features which are present but are not essential for the diagnosis.The liver is enlarged with rounded lower margin and soft consistency in about one-third

of cases. Histological examination shows fatty infiltration. The skin changes are not essential for the diagnosis of kwashiorkor. Large areas of skin show erythema, followed by hyperpigmenta-

178

tion. The skin becomes dry and hyperkeratotic. The epidermis peels off in large scales, exposing tender raw area underneath. It gives appearance of old paint flaking off the surface of the wood. The underlying raw skin is easily infected. The skin lesions are marked in areas of the body, most exposed to continuous pressure and irritation. Normally moist areas of skin appear sodden.

Petechiae or ecchymoses appear in severe cases. Dry, inelastic, mosaic skin with follicu-lar keratosis is not pathognomonic of kwashiorkor. This may be due to exposure to dust and in-clement weather.

Multiple nutritional deficiencies. As the nutritional deficiencies are generally multiple, anemia due to iron, protein, vitamin B12 or folate deficiency is often associated. Deficiencies of vitamin B complex factors, especially ariboflavinosis, are common. Keratomalacia due to vita-min A deficiency is reported in 10 to 20 percent of patients with kwashiorkor. Associated scor-butic changes manifest as bleeding gums, subperiosteal hemorrhage or even ecchymotic spots. Subclinical ascorbic acid deficiency is frequent in malnutrition. The clinical evidence of florid rickets may not be so evident in a case of protein-energy malnutrition when growth has stopped, since rickets is a disease of growing bones. As long as the child is not growing, skeletal changes of rickets may not be clinically overt. The latter become evident after the child is put on ade-quate calories and proteins, but without vitamin D supplementation. Cases of atrophic rickets may, however, be seen even with severe malnutrition.

Mild to moderate undernutrition1. Reduced physical activity.2. Slow gain in weight, arrested growth, underweight. 3. Thin buttocks, wrinkling of skin over front of thighs. 4. Chest circumference lags behind head circumference after the age of 1 year.

Marasmus1. Emaciated. Muscles markedly wasted, loose folds of skin wrapped over the bones.2. Body weight less than 60 percent of expected weight for age.3. Mid-arm circumference less than 12.5 cm.4. Dry inelastic skin, more prone to develop pyoderma.5. Distended abdomen.6. Irritable.7. Voracious appetite.

KwashiorkorEssential

1. Retarded growth.2. Edema of dependent parts.3. Mental changes (apathy, listlessness, lethargy).

Usual4. Impaired appetite.5. Hair thin, dry, brittle, straight, hypopigmented (reddish brown) “flag sign” with alternating

bands of black and brown hair.6. Diarrhea.7. Recurrent infections.8. Distended abdomen.

May be 9. Skin changes. Flaky paint dermatosis.10. Enlarged liver with rounded lower margin. Fatty infiltration of liver.

Role of malnutrition in infant mortality and early childhood deaths.

179

Infant mortality rate in India is very high and is presently computed as 79 per 1000 live births (1994). Of these 50 percent deaths occur in the first month of postnatal life. Most of these deaths are due to causes peculiar to infants, such as preterm birth and low birth weight. These babies are more vulnerable to suffering from infections in the neonatal period. Thus nutritional deficit is a major, albeit indirect, factor leading to high infant mortality rate. Mortality of chil-dren at the second year of life is also high due to combined effect of malnutrition and diarrhetic disease.

Nutrition and resistance to infection.The resistance of the human organism to infections is adversely affected in malnutrition.1) The skin and mucosa do not offer effective physical barriers against infection.2) Impaired chemotaxis, normal phagocytosis, defective candidacidal and bactericidal

capacity were observed in in-vitro studies of polymorphonuclear leukocytes.3) Cell mediated immunity. The bacterial infections, which require cell mediated im-

mune responses for protection against them, tend to be unusually severe in malnour-ished subjects. The thymus gland and thymus dependent lymphoid tissues are atro-phied and cases of PEM cannot be sensitized easily by several antigens. Delayed hy-persensitivity reactions, which recall previous sensitization, are also reduced.

4) Humoral antibodies. Circulating immunoglobulin levels are usually normal or ele-vated in malnourished subjects. Malnourished subjects without associated infections do not show elevation of immunoglobulin level. Elevation of IgA is attributed to fre-quent association of gastrointestinal and respiratory infections.

The number and proportion of B-lymphocytes are not altered. Humoral antibody re-sponse to a variety of immunizing antigens such as tetanus and diphtheria toxoids, polio and measles vaccine is adequate.

As the secretory IgA is generally reduced, recovery from infections is delayed and infec-tions tend to be severe in malnourished subjects. The period of infectivity is prolonged because of the increased duration of replication and shedding of pathogens. Systemic spread is also more likely.

Diagnosis and differential diagnosis. The thickness of adipose layer is the main diag-nostic criterion of hypotrophy and its degree. In hypotrophy of the I degree it is thin all over the body surface except face; in the II degree adipose layer disappear from abdomen, sometimes from chest, but is seen on extremities; in the III degree it disappears completely. In differential diagnostics it is necessary to take into account all diseases mentioned above (Etiology). In pa-tients with hypostature (even lag in height and weight) it is necessary to exclude different kinds of nanism both disproportional (chondrodystrophy, congenital osteopsathyrosis, vitamin D–re-sistent forms of rickets, grave vitamin D–dependent rickets) and proportional (hypophisial, hy-pothyroid, mitral, cerebral etc). It is necessary to remember about constitutional hyposomia. In some families tendency to delayed rate of growth exists because of different hereditary peculiar-ities of endocrine system. It’s considered that height of a healthy child may fluctuate within the limits ±1.5δ of healthy children height arithmetical mean. If their height oversteps these limits hyper– or hyposomia are spoken about. Hyposomia in the limits 1.5-2.5δ may be both normal variant and consequence of pathologic condition. When the child’s height is less than mean mi-nus 3δ, nanism is diagnosed.

Hypotrophy may occur both in children with normosomia, and with hyper– and hyposo-mia. Therefore permissible fluctuations of height for infant of first 6 months are 4-5 sm., till 3 years – 5-6 sm.; for body weight these figures are 0.8 and 1.5 kg (in ratio to arithmetical mean of these indices).

Management of protein-energy malnutritionPrinciples

180

1. The patient is evaluated for the severity of protein-energy malnutrition, presence or absence of systemic infections, other nutritional deficits such as vitamin deficiencies or anemia and fluid and electrolyte disturbances.

2. Epidemiological factors responsible for malnutrition are considered and attempt is made to eliminate them.

3. The intake of food is promoted by all available means. Locally available and culturally ac-ceptable foods, which the family can afford, are advised.

4. Complications of malnutrition, sequela and death are prevented and treated if present, by careful surveillance and prompt remedial action.

Nutritional therapy. Nutritional treatment is based on estimating of the degree of malnu-trition. But degree of body weight deficiency and deprivation of appetite not always correlates with seriousness of disease because of lesions of gastrointestinal tract and central nervous system (CNS). Therefore, two-phase feeding is the basic principle of nutritional therapy: 1) period of finding out (ascertaining) of food tolerance; 2) period of high-caloric diet. Food overload may lead to dyspepsia.

The important principles of nutritional therapy are the following: 1) use of easily assimi-lated food at the initial stages of treatment (breast milk, or formula) as dysbacteriosis, intestinal lactase insufficiency are often seen in patient with malnutrition; 2) more often food intake (7- in mild malnutrition, 8 - in moderate, 10- in severe); 3) adequate systemic control of nutrition, stool, diuresis, quantity of fluids taken in and injected, calculation of food load once a week, co-program – twice a week.

Period of finding out of food tolerance lasts in mild cases 1-3 days, in moderate – 3-5 days, in severe – 7-10 days.

Daily food volume in mild cases at first year of life must correspond to infant’s age and weight, caloric value – 110-130 Kcal/kg/day, in moderate and severe cases – initial food volume 2/3-1/2 of due volume, caloric value – 100-95 Kcal/kg/day. In very severe cases its necessary to begin with daily quantity of breast milk of 60 ml/kg and augmentate it by 20 ml/kg/day. Protein load in severe hypotrophy is 0.6g/kg. It is important to secure increase of weight from 3-4 day by 20g/day and more.

Lack of fluid is necessary to give orally (5% glucose solution, glucose–salt solutions). Parenteral feeding is used rarely (in vomits, diarrhea, ileus). Daily quantity of potassium both at enteral and parenteral feeding must be 4 mmol/kg (1.5 times higher than in norm), sodium – not more than 2-2.5 mmol/kg, as patients retent sodium easily, but have potassium deficiency. Ex-cessive quantity of potassium is given approximately 2 weeks. Restoration of normal volume of circulating blood and supportance and correction of disordered metabolism of electrolytes, stim-ulation of protein synthesis are the main tasks of first two days of therapy in severe hypotrophy. Use of 5% albumin, solutions of aminoacids during parenteral feeding is desirable. During pe-riod of high-caloric diet in mild malnutrition the infant receive approximately 140-160-180 Kcal/day, in moderate and severe cases – 180-200 Kcal/day. Proteins consist 10-15% of caloric value (in healthy infants – 7-9%), or 3.5-4 g/kg. Greater quantities of protein are not assimilated and therefore are useless, besides they may provoke metabolic acidosis, hepatomegaly.

Augmentation of food load is make after its calculation and under control of coprogram (once per 3-4 days).

All mentioned above – is schema of nutrition therapy of patients with malnutrition, but individual approach to diet is necessary for every sick child.

Organization of nursing. It’s possible to treat patients with mild malnutrition at home. Moderately and severe malnourished children should be treated in the hospital. The patient has to stay in light, spacious, regularly ventilated room. Air temperature must be not lower than 24-25o C, but not higher than 26-27o C, as infants may be overheated or supercooled easily. In ab-

181

sence of contraindications to walks it’s useful to go for a walk several times a day when temper-ature isn’t lower than -5o C. In autumn and winter hot water bottle on the legs is recommended. It’s very important to create positive emotions, to pay attention to prevention of cross infections, to bath a child every day (to 38o C); massage and gymnastics are necessary as well.

Lactose malabsorption. Some malnourished children do not tolerate milk because of as-sociated lactose intolerance. This should be suspected if the pH of the stools is lower than 5,5 on two separate occasions, while the child is on milk diet. In such children it is desirable to reduce the total lactose load in the diet by diluting the milk for 2 to 4 days or substituting a part of milk feeds by formulae based on lactose free milk protein (calcium caseinate), sugar and oil, soybean, meat or vegetable protein mixtures. Lactase ferment is also commercially available. Six drops of lactase enzyme (Nolac-Raptakos Bret) in 250 ml of milk hydrolyses the lactose in to glucose and galactose.

As a general rule, the diet prescribed for the child should be in the way that the family can afford to provide for the baby within its limited income, can be easily cooked at home, does not perish easily, is culturally acceptable and easily available in the local market. Expensive prestige foods may not necessarily be the most nutritious foods. Routine advice for giving fruit and eggs etc. should be made only after due consideration of the family’s economic constraints.

Treatment of associated nutritional deficiencies. Concurrent nutritional deficiencies should be treated promptly. Vitamin A deficiency is

not an infrequent association and is an important cause of blindness caused by keratomalacia. Skeletal manifestations of rickets are generally not florid during phases of arrested epiphyseal growth of bones in severe malnutrition. Biochemical evidence of rickets e.g., raised alkaline phosphatase is often present. These patients should therefore be treated with vitamin D.

Hypochromic anemia is usually associated and is treated with oral ferrous sulfate (200 mg/day). Folic acid (5-15 mg/day orally) and vitamin B12 (100 mcg/day) are indicated if red blood cells in the peripheral blood smear show macrocytosis.

Treatment of dehydration.A diarrhetic episode may precipitate acute onset of kwashiorkor. Diarrhea also produces

dehydration. Evaluation of dehydration in such cases is difficult. Loss of elasticity of skin may either be due to loss of the subcutaneous fat in marasmus or loss of extracellular water in dehy-dration. In dehydration, the oral mucosa feels dry to the palpating finger, which is gently rolled on the inner side of the infants cheek. There are no tears in dehydration. Dehydration should be appropriately treated.

Treatment of infections.The child should be clinically examined for the presence of infections and adequately

treated. Tuberculin test may become negative in severe malnutrition. This aspect should be given due consideration in evaluation for tuberculosis.

Prevention of death in malnourished infants and children during early phases of treat-ment.

Severely malnourished children may suddenly die due to following causes: I. HypothermiaII. HypoglycemiaIII. DyselectrolytemiaIV. Diarrhea and dehydrationV. Congestive cardiac failureVI. Infections

Sudden deaths should be averted by the following measures:

182

1. Malnourished children should be kept snugly covered during the night, even in warm tropi-cal climate since room temperature may fall in early morning. Their body temperature should be kept under check with the low-temperature-recording thermometer.

2. Intravenous infusion of 50 to 100 ml of 10 percent glucose solution should be given at the start of therapy to prevent hypoglycemia deaths.

3. Severely malnourished children with superimposed diarrhea or infections may develop se-vere hypokalemia and clinically manifest with weakness of abdominal, skeletal muscles and even of respiratory muscles. This may mimic poliomyelitis. The muscle weakness is re-versible on administration of potassium. ECG shows ST depression, T waves inversion and presence of U wave.

4. Dehydration should be treated promptly. Lactose content of the diet should be low in the ini-tial phases of treatment. This may be achieved by using formula based on calcium caseinate, corn or other vegetable oil and glucose in water or by adding 6 drops of lactase ferment (no-lac) in 150 ml of milk.

5. Sodium intake should be restricted to prevent sodium overload and water retention during the initial phases of treatment. Sodium in the diet may precipitate congestive heart failure.

6. Infections should be treated promptly and adequately. Children with severe malnutrition are more prone to have fulminating gram negative and opportunistic infections. Antibiotics should be chosen depending on their weight rather than the age.

5.1.3. Rickets

Rickets – is a disease of children of the 1st years, with disorders of bone production and deficiency of their mineralization. The main pathogenetic factors are deficiency of vit D and its active metabolites in a period of most intensive organism’s growth.

Etiology. There are the following predisposal factors for appearance of rickets:1. Deficiency of UV irradiation and staying out-doors, because 90% of endogenously

created vit D3 in organism is synthesized in skin under influence of sun beams. It is necessary to take into account that because of pollution of atmosphere of big towns, only minimal quantity of sun beams having antirachitic activity reaches the earth.

2. Food factors. Increase of frequency and severity of rickets was confirmed in groups of children receiving:a) non-adapted mixtures (to which vit D is not added);b) milk feeding only for a long time (1L of woman’s milk contains 40-70 IU of vit

D, cow’s milk - 5-40 IU), late prescription of additional food (1 g of egg’s yolk contains 140-390 IU of vit D);

c) vegetarian additional food predominantly (vegetables, porridges) without suffi-cient quantity of animal proteins and fats.

It is necessary to pay attention that not deficiency of vit D in food is a cause of rickets, but feeding not providing optimal conditions for entering of P and Ca from food and for pro-teins, lipids, microelements, other vitamins metabolism.

In particular, there is a lot of phytin acid in cereals, which binds Ca in intestine, and lignin as well which provide the same effect upon vit D and its metabolites. A great quantity of vegetables and cow milk nowdays contain plenty of phosphates (because of wide use of phos-phate fertilizers), that inhibits absorption of Ca.

3. Perinatal factors. Prematurity predispose to rickets because the most intensive income of Ca and P from mother to fetus takes place during last months of pregnancy, so a

183

baby born earlier than 30 weeks of gestation very often has osteopenia – more low content of mineral substances in bone. At the same time, they are need in greater quantity of Ca and P in food because of greater rate of postnatal growth compara-tively with mature children. Besides, prematurity, as well as placental insufficiency, is combined with much more low reserve in organism and more low level of vit D and its metabolites in cord blood.

4. Insufficient motor activity because of not only perinatal encephalopathies, but ab-sence of physical culture for blood flow of long bones is augmented during muscular activity.

5. Dysbacteriosis with diarrhea.6. Anticonvulsive prolonged therapy, which leads to speeding up metabolism of active

forms of vit D.7. Syndromes of malabsorption, chronic diseases of liver and kidney, which lead to dis-

orders of formation of active forms of vit D.8. Hereditary anomalies of metabolism of vit D, Ca and P.9. Ecological factors. Excess of strontium, zinc and other metals in soil, water, food

leads to partial substitution of Ca by these substances.10. Pigmentation of skin decreases intensity of creation of cholecalciferol in skin.Pathogenesis. Endogenous vit D3 (cholecalciferol) is synthesized in skin from 7-dihydro-

cholesterin under influence of ultraviolet rays. More than 60 its metabolites are created in organ-ism later, but nowadays, only 2 of them are considered to influence actively upon metabolism of Ca and P – 1.25-dihydrocholecalciferol and 24.25-dihydrocholecalciferol. Both of them are cre-ated in kidneys, and intermediate metabolit (25-hydrocholecalciferol) – in liver. The main ef-fects of active metabolites of vit D3 are stimulation of absorption of Ca and P in intestine and stimulation of bone’s mineralization. They activate synthesis of Ca-bounding proteins and in-crease activity of adenilatcyclase; that’s why we consider vit D3 to be hormone.

Hypocalcemia leads to increased function of parathyroid glands. Parathormone decreases (and vit D increases) reabsorption of phosphates in kidney tubules, stimulates absorption of Ca in intestine, resorbtion of Ca from bone and thus – liquidates hypocalcemia.

Insufficiency of vit D provokes aminoaciduria, leads to disorder of structure of organic matrix of bone (collagen). Disorder of ossification is seen in epiphysis, in metaphysis we see ex-cessive growth of osteoid tissue.

Clinical manifestations. Osseous changes of rickets can be recognized after several months of vitamin D deficiency. In breast-fed infants whose mothers have osteomalacia, rickets may develop within 2 mo. Florid rickets appears toward the end of the 1st and during the 2nd year of life. Later in childhood, manifest vitamin D deficient rickets is rare.

One of the early signs of rickets, craniotabes, is due to thinning of the outer table of the skull and detected by pressing firmly over the occiput or posterior parietal bones. A ping-pong-ball sensation will be felt. Craniotabes near the suture lines is a normal variant. Low-birthweight infants are particularly susceptible to the early development of rickets and to craniotabes. Palpa-ble enlargement of the costochondral junctions (the "rachitic rosary") and thickening of the wrists and ankles are other early evidences of osseous changes. Increased sweating, particularly around the head, may also be present.

Head. Craniotabes may disappear before the end of the 1st year, although the rachitic process continues. The softness of the skull may result in flattening and, at times, permanent asymmetry of the head. The anterior fontanel is larger than normal; its closure may be delayed until after the 2nd year of life. The central pans of the parietal and frontal bones are often thick-ened, forming prominences or bosses, which give the head a boxlike appearance (caput quadra-tum). The head may be larger than normal and may remain so throughout life. Eruption of the

184

temporary teeth may be delayed, and there may be defects of the enamel and extensive caries. The permanent teeth that are calcifying may also be affected; the permanent incisors, canines, and first molars usually show enamel defects.

Thorax. Enlargement of the costochondral junctions may become prominent; the beading of the ribs is not only palpable but also visible. The sides of the thorax become flattened, and the longitudinal grooves develop posterior to the rosary. The sternum with its adjacent cartilage ap-pears to be projected forward, producing the so-called pigeon breast deformity. Along the lower border of the chest develops a horizontal depression, Harrison groove, which corresponds with the costal insertions of the diaphragm. There may be a variety of other thoracic deformities, in-cluding those of the shoulder girdle.

Spinal Column. Slight to moderate degrees of lateral curvature (scoliosis) are common, and a kyphosis may appear in the dorsolumbar region of rachitic children when sitting. Lordosis of the lumbar region may be seen in the erect position.

Pelvis. In children with lordosis, there is frequently a concomitant deformity of the pelvis, which is also retarded in growth. The pelvic entrance is narrowed by a forward projection of the promontory the exit, by a forward displacement of the caudal part of the sacrum and the coccyx. In the female, these changes, if they become permanent, add to the hazards of childbirth and may necessitate cesarean section.

Extremities. As the rachitic process continues, the epiphyseal enlargement at the wrists and ankles becomes more noticeable. The enlarged epiphyses can be seen or palpated but are not distinct in roentgenograms because they consist of cartilage and uncalcified osteoid tissue. Bend-ing of the softened shafts of the femur, tibia, and fibula results in bowlegs or knock-knees; the femur and the tibia may also acquire an anterior convexity. Coxa vara is sometimes the result of rickets. Greenstick fractures occur in the long bones; often there are no clinical symptoms.

Deformities of the spine, pelvis, and legs result in reduced stature, rachitic dwarfism.Ligaments. Relaxation of ligaments helps to produce deformities and partly accounts for

knock-knees, overextension of the knee joints, weak ankles, kyphosis, and scoliosis.Muscles. The muscles are poorly developed and lack tone. As a result, children with

moderately severe rickets are late in standing and walking. Potbelly depends to a large extent on weakness of the abdominal muscles; weakness of the gastric and intestinal walls may contribute.

Differential diagnosis: Vit D-dependent rickets of I type: defect of 25-hydroxyvitamin D-I-hydroxylase in kidney lays in its basis. Laboratory signs are following: hypocalcemia, hy-pophosphatemia, high levels of parathormone in blood, increased activity of alkaline phos-phatase, aminoaciduria, gllucosuria. Usual doses of vit D are ineffective.

Vit D-dependent rickets of II type: almost the same, but total alopecia and retarded growth are present; level of 1,25 (OH)2 D3 is normal, but hypocalcemia and hypophosphatemia are preserved.

Phosphat-diabetes – defect is not quite clear, but it concerns reabsorption of phosphates in renal tubules and decreased activity of convertion of 25 (OH) D3 in 1,25 (OH)2 D3. There are O-shaped legs; hypophosphatemia may be revealed by chance from the 1st month of life, signs of hypocalcemia, hyperplasia of osteoid tissue, myopathy are absent, level of blood Ca is normal or slightly decreased, parathormone in blood is normal, alkaline phosphatase elevated a little bit.

Hypophosphatasia – the length of tubular bones is diminished, disorders of ossification of all skeletal bones, activity of alkaline phosphatase in blood is very low. Hypercalcemia, nephrocalcinosis, renal insufficiency may be seen.

Treatment. Rational diet, walks outdoors, massage and gymnastics. In initial stage of rickets 1.300-2000 IU of vit D2 is enough (total dose 100-120 000 IU). In moderate and severe rickets it’s necessary to prescribe 3 - 4 000 IU/d (200-400 000 IU). Criterion of finishing the treatment is normalization of laboratory findings. Dose of calcifediol (25(OH)D3) and calcitriol

185

(1,25(OH)2D3) are 10 and 1 mcg correspondently. After the course of treatment it’s necessary to give preventive dose (400 IU/d). UV irradiation is effective. Prescription of citrates is of great use.

Prevention – may be antenatal and postnatal, specific and non-specific. Specific preven-tion is not indicated in women elder 35 years, because of excessive Ca deposits in placenta and fetal hypoxia, atherosclerosis in women.

Specific postnatal prevention we begin from 2nd week with 400 IU of vit D all year round + vit C 0.03 g + B1, B2 - 0,001 g, B5 0.003 g 2 weeks in a month. It is possible to alternate vit D with UV irradiation, after course of which it is not necessary to give vit D 3-4 weeks. Once in 2-3 weeks it is necessary to provide test of Sulkowitz, if it is positive, vit D must be abolished.

Tetany is a disease of infants characterized by disposition to tonic and tonico-clonal convulsions.

Pathogenesis. Association of tetany with rickets has been observed long ago, but it was proved only in 70 s. when low level of 25-hydroholecalciferol was revealed in all children with tetany.

Clinical features. There are latent and manifest forms of tetany.Most frequent symptoms and signs of latent tetany:- Chvostek’s sign – tapping in anterior to the ear elicits contractions of mimic

muscles;- Trousseau’s sign – pressing the shoulder with an elastic tourniquet for 3 min

causes convulsive contraction of fingers (hand of obstetrician);- Maslov’s sign– if we prick the child apnoe at the height of inspiration will be

seen;- Lust’s sign – quick adduction of foot after knocking under the head of fibula.Manifest tetany:- Laryngospasm – this is manifested with hoarse inspiration while crying and ap-

noe for some seconds; at first pallor of skin, than cyanosis, unconsciousness, clonic convulsions appear. The attack ends with deep sonorous inspiration after which the child cries and in some minutes falls asleep. In severe cases death may occur as a result of cardiac arrest.

- Carpopedal spasm – spasm of distal muscles of arms and foots; it may be either short-term or may be seen for some hours and even days.

- Eclampsia – clonic convulsions with unconsciousness after short-term tonic con-vulsions.

Diagnosis is easy. In all patients concentration of ionized Ca is decreased (<0.9 mmol/l, N=1.1-1.4), decrease of total Ca is seen more rarely.

Differential diagnosis. In hypoparathyroidism which is very rare in babies, hypocal-cemia and hyperphosphatemia are usual. In renal osteodystrophy there are signs of renal insuffi-ciency. Eclamptic form is necessary to differentiate from epilepsy.

Treatment. In laryngospasm it is necessary to create a dominant focus of excitement in the brain (irritation of nasal mucosa, skin with a prick, tap). In convulsions – 0.5% seduxen 0.1 ml/kg, MgSO4 0.5 ml/kg, natrii oxybutyras 0.5 ml/kg are injected i.m. Restriction of cow milk because of great quantity of phosphates is of use. Orally 5% Ca gluconate, lactate, chloride 1-2% are given. After 3-4 days – vit D 2-4 000 twice a day is prescribed.

Hypervitaminosis D

186

Pathogenesis – direct toxic action upon cellular membranes, metabolism, and conse-quences of hypercalcemia (concentration of 1,25 (OH)2 D 3 is normal, 25 (OH)D3 – significantly evaluated).

Clinical picture – in acute form severe intoxication, anorexia, muscular flabbiness, vomit, headache, polyuria, dehydration, constipation, excitement and than apathy up to coma, convulsions, central paralysis are typical.

In chronic hypervitaminosis disorder of sleep, irritation, perspiration, pallor of skin, polyuria and polydipsia, dehydration, proteinuria, pyuria and other signs of nephrocalcinosis, pains in bones, constipation, calcification of the vessels, retinopathy, myocardiopathy, renal in-sufficiency, hypertension are present.

Treatment: i.v. infusion of albumin, 5% glucose, Ringer’s solution, cocarboxilase, pred-nisolone (2mg/kg with gradual diminishing of a dose during 10-14 days), vit A (5-10000 IU/day), phenobarbital, vit C (100-200 mg/day), vit E, furosemid (1 mg/kg 3 times a day), 3% chloride ammonium (1 teaspoonful 3 times a day), chlolestiramine (0.5 g/kg 3 times/day), al-magel, xidiphone (10-15 mg/kg 2 times/day), trilon B 50 mg/kg 2-3 times/day orally, in severe cases –i.v. are used.

5.1.4. Infections of urinary tract. Acute and Chronic Pyelonephritis

Renal development and function Renal development: kidneys start to develop between 3-4 weeks of fetal age. By the 15 th

week minor calyces, renal papillae and renal lobes are present and by the 22nd week medulla and cortex are clearly demarcated and a third of nephrons are formed. Nephron induction ceases at about the 26th week of gestation. The last generations of nephrons are situated in the cortex and they are immature. These have underdeveloped proximal tubules and short Henle’s loops. The full complete set of nephrons is present by the 36th week. The neonatal kidney shows marked nephron heterogenecity, which disappears by the end of the first year of life. Dysgenesis at vari-ous stages of development accounts for the large variety of the congenital anomalies of the kid-ney and urinary tract. The growth of kidneys parallels general somatic growth but the latent ca-pacity of the kidneys to grow continues well into adulthood. When one kidney is removed, the other kidney hypertrophies by increase in the size of individual nephrons.

In the human fetus, urine formation is believed to start between 9-12 weeks of gestation, initiating urine formation and contributing to amniotic fluid. In later stages of pregnancy, the amniotic fluid is largely derived from fetal urine.

Renal physiology. Glomerular filtration depends upon the higher pressure in afferent ar-terioles. The filtration barrier is constituted by the endothelium with slit pores, basement mem-brane and epithelium with its interdigitating foot processes. Filtration of macromolecules de-pends upon the molecular size, shape as well as their electrical charge. Electrostatic hindrance is provided by fixed negatively charged component of glomerular capillary wall. Podocytes carry a rich surface coat of sialoproteins, which are highly negatively charged. The filtrate contains all the diffusible and ultrafiltrable substances present in plasma. Small quantities of protein are present in the filtrate amounting to 1mg/dl. Most of it is reabsorbed in proximal tubules. Nor-mally about 20% of plasma appears as filtrate. As it flows down the tubule, bulk of it is reab-sorbed so that finally about 0.5 percent of the amount filtered is excreted as urine.

International classification of diseases, traumas and death’s causes of 10 th revision fore-sees the diagnosis “urinary infections without other indications”. Indeed, sometimes leucocy-touria, mild proteinuria and bacteriuria are revealed in patient with acute respiratory infection (ARI) or pneumonia, but they quickly disappear on the ground of rational therapy. There are

187

these cases when the diagnosis of urinary tract infection (UTI) is possible. But this diagnosis must be established after a thorough observation of the patient and urineanalysis. The diagnosis of UTI is possible on the ground of isolated bacteriuria as well. Asymptomatic bacteriuria is ob-served in 1-2% of schoolgirls, but 1/3 of them has vesicourethral reflux (VUR). It is necessary to investigate such children repeatedly including USE.

Infections of the urinary tract are a significant cause of morbidity in girls and, more im-portantly, irreversible renal damage in association with abnormalities of the urinary tract and vesicourethral reflux. The precise incidence of urinary tract infections is not known since urine-analysis is often not performed as a part of diagnostic evaluation, particularly in infants in whom clinical features of UTI are non-specific.

In the newborn period, the incidence of UTI is about the same in boys and girls, since 1) the route of infection may be hematogenous and 2) boys have a higher incidence of urinary tract anomalies, particularly posterior urethral valve. Beyond infancy the incidence of UTI is higher in girls. Asymptomatic bacteriuria is also more frequent in girls, although its significance is not clear.

Cystitis. Inflammation of cystic mucous membrane is often caused by E. coli or St. au-reus. Infection may penetrate the urinary bladder by the following routs:

1) descending route from kidneys;2) ascending route from urethra;3) hematogenic route ;4) contact (the rarest route).

Etiology. Anatomic peculiarities of the urinary tract in girls (short and wide urethra) pre-dispose to higher incidence of cystitis in them than in boys, since ascending infection prevails. If hygienic regimen is insufficient or intestine dysfunction occurs, there is high possibility of mi-crobic penetration through the urethra. Enterobius vermicularis plays an important role in ap-pearance of cystitis: during the sleep they crawl into the urethra and, probably, the urinary blad-der and contaminate it.

Possibility of abacterial cystitis (allergic or viral) is proved. Hemorrhagic cystitis during adenoviral infection (11th and 21st types) may occur, as well as complication of therapy (e.g. cy-clophosphan). Appearance of cystitis in girls after exposure to cold (bathing in cold water) is well known. Cystitis may occur in appendicitis because of pelvic position of the appendix.

Morphologically cystitis may be catarrhal, purulent, hemorrhagic, pseudomembranous-necrotic and gangrenous.

Clinical picture. The illness begins with infant’s anxious behavior. Pain in the pubic re-gion, disuric symptoms appear: imperative inclination to micturition, frequent (pollakiuria), painful with small portions micturition. Sometimes enuresis appears. If the infant can not speak it is possible to notice disuric symptoms by frequent micturition, anxiety and cry, after which wet swaddling clothes appear.

The course of acute cystitis may be different: from mild to severe forms with intoxica-tion. Improvement in acute cystitis comes in 3-5 days, the urine becomes normal. If at correct treatment urine does not normalize, urologic investigation including intravenous urography is necessary.

Diagnosis and differential diagnosis. The diagnosis is based on excretion of turbid urine, sometimes with clots of fresh blood, that is the sign of severe inflammatory process. There are the traces of protein, numerous leukocytes, microbes and fresh erythrocytes in the urine; besides it there may be a large amount of squamous epithelium. Pathogenic microflora is observed in inoculation. It is necessary to differentiate cystitis from vulvitis, vulvovaginitis of trichomoniasal origin, and from phimosis and balanitis in boys. It is necessary to examine exter-

188

nal genitals thoroughly. If vulvitis is present, redness of vulva, traces of vaginal discharge on the underwear may be seen. It is possible to differentiate the diseases finally by investigation of 3 portions of urine taken from the urinary bladder with a sterile catheter. If leukocytes have vagi-nal or vulval origin, they would be absent in urine taken from urinary bladder with a catheter.

Dysuric disturbances may be the first sign of acute appendicitis in its retrocecal, retroperitoneal and pelvic position. Differential difficulties are stipulated by absence of tender-ness on palpation and tension of anterior abdominal wall muscles, and Schetkin-Blumberg sign may be negative. Instead of it there is muscular tension and marked tenderness in right lumbar region, positive Goldflame-Pasternatsky sign. Rectal digital investigation is of great use for cor-rect diagnose with the help of which it is possible to reveal overhanging of infiltrate at the right side.

It is necessary to differentiate cystitis from primary and secondary forms of pyelonephri-tis (PEN). It is considered that if urinary microbes are surrounded with antibodies, the diagnosis of PEN must be established (immunofluorescent bacterioscopy). If there is granular cystitis, it is necessary to exclude tuberculosis.

Treatment. As for the regimen, it must be bed rest. Irrigation with warm 0.02% solution of furacillin, decoction of matricary as well as physiotherapy are indicated.

For augmentation of diuresis it is useful to give plenty of water to the child. The diet is usual, extractive and spicy food is excluded, mineral water is useful. If anorexia, vomiting and dehydration are present, it is necessary to inject solutions of glucose and Ringer’s solution (2:1) intravenously. Antibiotics or sulfonamides, analgesics are prescribed.

Prognosis is favorable in correct treatment. All pathologic phenomena disappear in 1-2 weeks.

Pyelonephritis (PEN). This is microbial inflammatory kidney disease with lesion of calyces, pelvises and later interstitial tissue of parenchyma and tubules. According to different authors PEN is revealed in 2-3% of grown-up persons; the disease begins in early childhood in 50-70% of cases.

Etiology. Bacteria which caused PEN are, as a rule, intestinal commensals, that is mi-crobes living in the intestine of healthy persons: E.coli, Proteus, Enterococci, Klebsiellas, more rarely St.aureus or epidermidis, Pseudomonas aeruginosa.

There are particular varieties of E.coli and Proteus in urine: E.coli with antigens 01, 02, 04, 06, 075 and K-1, K-2 antigens; Proteus rettregi or mirabilis. The change of bacterial strain or even species of pathogens is seen in the course of disease; not rarely recurrent exacerbations are caused by mixed bacterial flora.

Absence of bacteriuria in patients with pyelonephritis after antibacterial therapy does not testify to the fact that bacteria do not play the main role in pathogenesis of subsequent kidney le-sion. It has been proved that bacterial antigens (lipopolysaccharides) are revealed in kidneys of sick persons 5-6 months after the disease exacerbation in absence of bacteriuria during 2-5 months. Prolonged circulation of amorphous bacterial antigen in the kidneys of patients with pyelonephritis may create conditions for more easy reinfection than in healthy children. L-forms of bacteria (so called protoplasts, that is bacteria without cell membrane) play an impor-tant role in pathogenesis of chronic pyelonephritis. Protoplasts perish in hypotonic media of or-ganism tissues, but in hypertonic medium of renal medulla or in conditions of intraepithelium parasitism they may survive and turn into vegetative form, e.g. under the influence of intercur-rent infections.

Viruses, Mycoplasms, Chlamydias play the role in persistence of bacterial antigens in the kidneys.

Chronic renal diseases (first of all PEN) in the family, especially in the mother (particu-

189

larly PEN during pregnancy) are the most important predisposing factors for development of PEN.

Pathogenesis. According to contemporary investigations, there are disorders of urody-namics in great majority of patients with PEN. It is considered that disorders of urodynamics precede the appearance of PEN, which can occur only in their presence. Urogenic (ascendant) way of contamination is the main one for the infection to get into pelvises, tubules and intersti -tium. The doctrine about reflux (backward flow) explains how the microbes get into the kidney when usual urine flow is from top to bottom.

Reflux are pathologic conditions appeared as a result of anatomical defects, which pre-vent urine flow, or disorders of nervous regulation of muscular tonus of different parts of the urinary system. Vesicourethral (VUR) and pelviorenal (PRR) reflux are known. The latter is di-vided in pelvio-tubular and fornical.

There are 5 grades of VUR according to International classification: grade I – contrast goes only into ureters during cystography; grade II – contrast fills unchanged ureter, pelvis and calyces; grade III – mild or moderate distortion and/or curve of ureter, moderate distortion of pelvis, smoothed picture of calyces; IV grade – marked distortion and/or curve of ureter, pelvis, calyces, total disappearance of acute angles in the calyx picture, but preservation of papillary picture in the majority of calyces; V grade – strongly pronounced distortion and curve of ureter (megaureter) and calyces, loss of papillary picture of calyces.

VUR may be stipulated by:1. Anatomical defects (diverticulum or doubling of urethra; short intramuscular part of urethra,

that is part in a wall of urinary bladder); muscular and nervous pathology in the region of Li-eto triangle (triangle among foramens of ureters and urethra) etc.

2. Cystitis. 3. Disorders of nervous regulation of muscular wall and bladder sphincters (so-called neuro-

genic bladder – NB).The term “neurogenic bladder” unites different forms of disorders of reservoir and evacu-

ator urinary bladder functions, which develop because of nervous system lesions at different lev-els (from cerebral cortex to intramural apparatus). The most severe forms of NB with VUR of III-V degree are seen in myelodysplasias (according to some authors 1/3-1/2 of such patients have myelomeningocele), injuries (including birth spinal injury), tumors, inflammatory–degen-erative diseases of the spinal cord.

According to contemporary theories the independent pathology – reflux nephropathy – exists, which is prerequisite not only for development of PEN, but arterial hypertension as well. It is characterized by gross renal cortical scarring predominantly at both poles. The scars are usually sharply demarcated from the adjacent unscarred parenchyma. The underlying calyces show clubbing and loose their normal concave shape, which is due to papillary distortion and re-traction following scar contraction. Such scarring occur early in the life while the kidney is still growing and formation of fresh scars after the age of 5 years is uncommon.

VUR of grade I may disappear in 89% of cases, grade II – in 86%, III – in 83%, IV-V – in 41%. Severe fetal VUR may lead to great loss of renal parenchyma and renal insufficiency even in the newborn. In newborns VUR is invariably complicated by infection and further PEN.

The lesions of interstitial renal tissue are the second condition for appearance of PEN (the first one is disorder of urodynamics). Viral and Mycoplasma infections, drug lesions (e.g. hypervitaminosis D), dysmetabolic nephropathies may be their cause. As a result of the above metioned obstructive disorders, which form VUR, lesions of renal interstitial tissue, so called “locus minoris resistaentiae”, are formed in the kidneys, and PEN may appear on the ground of reduced organism reactivity.

Intercurrent diseases of the genital organs (vulvitis, vulvovaginitis), dental caries, chronic

190

cholecystitis, colitis, tonsillitis may be the cause of bacteriuria and bacteriemia as well as pathol-ogy of the gastrointestinal tract.

Autoallergy plays the role in pathogenesis of chronic PEN. Detection of antibodies to Tamm-Hoursefield protein in the blood, development of hypersensitivity reaction of delayed type indicates it.

Thus, the following factors play the role in pathogenesis of PEN:1) disorders of urodynamics;2) bacteriuria;3) preceding lesions of interstitial renal tissue;4) disorders of the organism reactivity.

The role of hereditary factors in pathogenesis of chronic PEN is obvious. In particular, chronic PEN may be the manifestation of hereditary disorders of metabolism and tubulopathies, hereditary immune defects, fetopathies which lead to renal dysembryogenesis etc.

Due to uneven bacterial invasion pathological process in the kidneys is not diffuse and may be even one-sided (unilateral).

ClassificationThere are the following forms of PEN: according to pathogenesis – 1) primary; 2) secondary: a) obstructive, in anatomic anomalies of the urinary tract;

b) in renal dysembryogenesisc) in dysmetabolic nephropathies

according to the course - 1) acute; 2) chronic: a) manifest recurrent form;

b) latent form. according to the period - 1) exacerbation (active); 2) development of reverse (partial remission). according to the function - 1) without functional renal disorders; 2) with functional renal disorders;

3) chronic renal failure.Chronic PEN is diagnosed when clinical and laboratory signs of PEN are observed for

more than 6 mo.Clinical picture. Clinical picture of acute PEN in typical case is characterized by:

1) pain syndrome (abdominal or lumbar pains);2) dysuric disorders (imperative inclinations, pollakiuria, pain or sensation of itch, burning dur-

ing micturition, noctiuria, enuresis);3) symptoms and signs of intoxication (elevation of temperature with chill, headache, flabbi-

ness, weakness, bad appetite, pallor with mild icteric tint). The pain is markedly intensified in change of body position, jumps, inclines and is re-

laxed in warming of the lumbar region. Edema is absent, as a rule, blood pressure (BP) is nor-mal, diuresis is moderately increased. The urine is turbid, with an unpleasant smell.

Palpation of the ureter projection at the side of the lesion, in the renal region, in the angle between the vertebral column and the last rib, is painful, as well as thrashing of lumbar region.

In urine there is proteinuria (to 1%), neutrophil leucocyteuria, microhematuria (in 25-30%), large amount of cellular epithelium and sometimes of salts. Daily dyuresis is moderately increased. Specific gravity of the urine is normal or slightly decreased, its reaction may be both acid (more often) and alkaline. Cylindruria is absent in great majority of cases, since there is no such important condition of cylinder formation as diuresis diminution.

Common symptoms prevail in clinical picture of acute PEN in infants: flabbiness or anx-

191

iety, anorexia, hyperthermia, vomiting, constipation or dyspepsia, loss of weight, sometimes jaundice, convulsions, meningeal signs. Dysuric manifestations may be mild. Marked suscepti-bility to generalization of infection, rapid development of disorders of water-salt, protein and other kinds of metabolism, disorder not only of renal function, but also liver function with fur-ther appearance of severe intoxication and dehydration, collapse may be seen. The clinical pic-ture resembles sepsis.

At the same time in infants with chronic PEN only such general symptoms as lack of ap-petite, insufficient augmentation of body weight and height, retardation of psychomotor devel-opment, subfebrile temperature may be revealed.

In elder children the signs of intoxication prevail as well: apathy, flabbiness, headaches, bad appetite, disorders of nutrition, subfebrile temperature, abdominal pains of uncertain local-ization, rarely pains in lumbar region with minimal dysuric disorders or even without them. PEN may have latent course with minimal changes in the urine. There are chronic foci of infection in great the majority of patients.

ComplicationsApostematous nephritis (lots of abscesses in kidneys). This is acute septic disease with

high, more often of hectic type, temperature, marked intoxication and poor general condition (nausea, vomiting, convulsions, dehydration).

Carbuncle manifests with squeezed calyces and pelvis or with amputation of one or few calyces on excretory urogram (as if it were tumor).

Paranephritis. Lumbar pain is the main symptom, leucocytes appear in the urine later. High temperature may occur. Goldflame-Pasternatsky sign is positive. Sometimes the child lays in forced position with his leg banded in hip joint without limitation of mobility in it. This posi -tion occurs because of lumbar muscle contracture, which is stipulated by the inflammatory process. Fluoroscopy demonstrates limitation of lung margin’s mobility and absence of renal displacement during respiration is seen. Swelling in the lumbar region appears more lately.

These complications of acute PEN in children are seen more rarely than in grown-up per-sons.

Nephrocalcinosis, nephrogenic hypertension, chronic renal failure due to arteriosclerotic kidney are complications of chronic PEN.

Diagnosis and differential diagnosis. In acute course or in exacerbation of chronic process there are no difficulties in diagnosis. It is necessary to carry out the following complex of investigations:

Urineanalysis once per 7-10 days. If there are no clear findings for diagnosis, it is neces-sary to carry out Nechiporenko (Amburgeau, Kakovskiy-Addis) test. Revealing of the so-called “active leukocytes” in the urine sediment has some auxiliary significance.

Urine inoculation (not less than 3 times) with definition of microbe sensitivity to antibi-otics. It is necessary to wash external genital organs with sterile tampons moistened in furacillin (including boys without circumcision of prepuce) and than with sterile water because they may be contaminated with microflora. It is important to wash girls from the front to back.

Determination of bacteriuria degree. It is considered significant if there are 100000 of microbes in 1 ml of urine.

Determination of renal functional condition with 1) Zimnitsky’s test once per 7-10 days; 2) Reberg’s test; 3) determination of secretory renal function and renal blood flow. Besides it is desirable (in specialized hospitals it is obligatory) to determinate the indices, which characterize the function of distal nephrons (ammonia, filtrated acidity of urine), proximal tubules (β2-mi-croglobulin in urine, proteinuria, calciuria, phosphaturia), Henle’s loop (osmotic concentration of the urine).

Biochemical analyses of blood. Total protein, cholesterole, residual nitrogen are normal

192

for a long time in PEN. Revealing of dysproteinemia (with elevated levels of α2- and γ-globu-lins), rise of cialic acids, mucoproteins, positive C-reactive protein reaction are of diagnostic value.

Ultrasonography of kidneys for establishing diagnosis of VUR.X-ray and other investigations of the urinary tract 1 month after the acute period. De-

scending urography should be carried out in every patient with PEN (especially in infants). It is possible to reveal deformation or distortion, spasm of calyces or other parts of the urinary tract, disorder of excretory function of one or both kidneys, sometimes reflux. Radioisotope renogra-phy is useful in all patients with PEN as it gives possibility to evaluate excretory and secretory renal functions, asymmetry of their lesion. Cystography and cyctoscopy are obligatory for all children with dysuric disorders, enuresis.

Drawing up the genealogy with indication of all persons with renal pathology.It is necessary to differentiate PEN from renal tuberculosis (contact with patient with tu-

berculosis is important). Hematuria and mycobacteria tuberculosis are revealed in the urine.Differential diagnosis with glomerulonephritis is the most important.

Differential diagnostic signs of acute diffuse glomerulonephritis and acute pyelonephritisSigns Acute glomerulonephritis Acute pyelonephritisOnset of disease 2-3 weeks after angina, scarlet

fever, ARIOn the ground of acute bacte-rial and viral infections

Dysuric disorders Not typical Typical Lumbar pains Present in 25-30% of patients Present in the majority of

school age childrenTemperature As a rule, normal or subfebrile As a rule, febrile or subfebrileUrinary syndrome Hematuria and cylindruria

(sometimes leucocyturia in first 2-3 days), oliguria. Specific gravity is normal or elevated.

Leucocytouria, normal or ele-vated diuresis, monotonous, de-creased specific gravity of the urine in different portions

Urine inoculation Always sterile Positive in 85% of casesResidual nitrogen, urea Elevated Normal Edemas Typical Absent Hypertension Present in most patients Is not typical

Main indices of renal function:FiltrationReabsorption

Secretion

DecreasedNormal

Normal

NormalMore often normal, but may be decreased

More often decreasedMorphologic changes of kid-neys

Glomerular capillaries lesions are typical, proliferation of Bowman’s capsule cells

Primary lesion of interstitial re-nal tissue

It is established at present that PEN is a typical complication of hereditary tubulopathies, therefore it is useful to exclude these diseases by carrying out the following tests: daily excretion with urine of amino acids (norm 0.001-0.005g/kg), calcium (0.004-0.008g/kg, but less than 300mg/d), phosphates (0.01-0.04g/kg, but less than 1g/day), oxalates (0.001g/kg, but less than 40mg/day), citrates (0.006-0.012g/kg), uric acid (<0.001 g/ml of urine, not more than 2g/day), titratable acids (1-2mmol/kg), ammonia (1-3mmol/kg), urea (0.3g/1g of protein in diet).

It is necessary to differentiate PEN from vulvitis, vulvovaginitis. If changes in urine do not disappear after the treatment of these diseases it is necessary to investigate the girl in suspi -

193

cion to PEN.It was proposed to differentiate PEN from infection of urinary tract with the help of urine

bacterioscopy with labeled antisera to immunoglobulins G and A. If microbes are covered with immunoglobulins, the diagnosis of PEN is established.

Treatment. It is necessary to hospitalize the child in acute period. Bed rest in absence of renal insufficiency is indicated during the fever period and 3-4 days more.

If intoxication is present, the treatment is begun with forced diuresis. Daily quantity of liquid 1.5 times exceeds the age requrements. The patients receive supplementary liquid with water–melon, cranberries or red bilberries water, juices etc. Fresh vegetables and fruits, espe-cially melons, vegetable marrow are of use. In acute period it is expedient to give milk-vegetable diet with moderate limitation of protein (1.5-2g/kg) and salt (to 2-3g). Diet limitations depend on salts in the urine sediment, its acidity.

In painful syndrome antispastic therapy is prescribed (no-spa, baralgin, papaverin).If reflux exists, forced micturitions are useful (every 1.5-2 hours in squatting position).Antibacterial drugs are necessary with preliminary urine inoculation and determination of

microbe sensitivity. In presence of intoxication the treatment is begun with antibiotics – ampi-cillin, cefalosporins, and carbenicillin injected i.m. 3-4 times/day. Aminoglycosides are antibi-otics of reserve. They are prescribed only if antibiotics mentioned above are not effective. Tak-ing into account their potential nephrotoxicity, it is necessary to administer them twice a day in middle therapeutic doses and not longer than for 7 days. Oliguria, renal insufficiency are con-traindications for their administration. Antibiotics are used untill intoxication and temperature disappear. After the antibiotics the course of lactobacterin is necessary.

Nitrofurans (5-8mg/kg 4 times/day), nalidixic acid (negram, nevigramon 50-60mg/kg 4 times/day), 5-NOK, nitroxolin (8-10mg/kg 4 times/day), biseptol (2mg/kg of trimetoprim twice a day), sulphonamides (0.1g/kg 4 times/day) are used after a course of antibiotics.

After 2-4 courses of antibiotics alternative courses of uroseptics are prescribed for 3-6 months in acute PEN and 6-9 months in chronic PEN (10 days/month). If there are no signs of intoxication and high temperature, it is possible to begin the treatment with uroseptics without preliminary antibiotic therapy.

Phytotherapy is usually used. The types species are prescribed: diuretic, litholytic, anti-septic, antiinflammatory, consolidating vascular wall.

Physiotherapy is indicated as well. UHF-therapy or ultrasound therapy (5-8 treatments) are carried out in the acute period, later SHF-therapy (6-8 treatments) and then electrophoresis with 1% solution of furadonin and ampicillin (10 treatments).

It is necessary to reveal and treat in proper time the foci of chronic infection and sensibi-lization (dental caries, chronic tonsillitis, cholecystitis, helminthiasis, especially enterobiosis).

Treatment of VUR may be surgical of conservative. Ultrasound control of VUR is neces-sary every 6 months. Surgical correction of obstructive anatomical disorders is of great use, but antireflux operations in functional obstructions give the same effect as conservative therapy ac-cording to international group of experts.

Prognosis depends on the character of disease (primary or secondary), intensity of treat-ment, presence of accompanying diseases. If in secondary PEN it is impossible to liquidate the cause of urostasis, long term prophylaxis may be necessary to keep the urine sterile. At the same time, especially in infants, complete recovery is possible. Primary PEN is curable in 40-60% of cases, primary chronic PEN – in 25-35% of cases. But prognosis as to complete recovery is nec-essary to put very carefully after 5 years of observation and determination of renal function.

5.1.5. Interstitial nephritis. Tubulopathies

194

Interstitial nephritis (IN) – it is abacterial inflammation of renal connective tissue with following involvement in pathologic process of tubules, blood and lymph vessels of renal stroma. Frequency of IN in childhood is not established.

Etiology. There are various causes of IN: viral, Leptospirosa and Mycoplasma infections, drugs lesions (antibiotics: ampicillin, oxacillin, meticillin, carbenicillin, tetracyclin, ce-falosporins of first generation, aminoglycosides, rifampicin, polymyxin, vancomycin, ampho-tericin B; diuretics: diacarb, hypothiazid, furosemid; non-steroid anti-inflammatory drugs: metindol, aspirin, analgin ; all sulfonamides, aminocapronic acid, boric acid, mannitol, hemodes, rheopolyglukin, cytostatics, bismuth, iron, copper etc.), hypervitaminosis D, poisonings, burns, intravascular hemolysis, shock, collapse, tubercular intoxication, dysmetabolic disturbances. Drug lesions on the ground of hereditary peculiarities, burns, chock take first place in the etiol-ogy of acute IN, as well as dysmetabolic nephropathies in etiology of chronic IN.

Pathogenesis. Injury of tubule basal membrane with drugs, toxins, viruses, formation of complex antigens (alien antigen and antigen of tubules), hemotaxis to the place of lesion of com-plement, leukocytes, immune compleces are of particular importance in pathogenesis of IN.

In some patients synthesis of autoantibodies to basal membrane proteins is of great sig-nificance (for example, to tubule glycoprotein of Tamm-Hoursefield). This protein and antibod-ies to it appear in the patient’s urine as well. There are signs of atopia in some part of children – high level of blood IgE, its deposits in perivascular infiltrates in interstitium. Hereditary and ac-quired defects of phagocytic link function play a predisposal role in development of IN.

Chronic IN appears more often in hereditary dysmetabolic nephropathies because of ac-cumulation of urates, oxalates in interstitium, which cause mononuclear infiltration, stroma edema, release of inflammation mediators from leukocytes, activation of kynin system and fac-tor XII, and, as a result, blood coagulation.

Inflammation and edema in interstitial tissue of renal medullar layer leads to mechanical pressure of vessels, tubules, diminishes renal blood flow and elevates intratubular pressure; olig-uria, azotemia are observed even in intact glomeruli. Involvement of tubules in inflammatory process leads to theirs dystrophy, necrosis, disorders of function – isohypostenuria, acidosis, polyuria, hypokalemia.

Clinical picture. Acute IN may develop on the ground of acute disease (ARI, sepsis, chock); oliguria, dysuria, nausea, headache, pain in lumbar region appear, that is, acute renal failure (ARF) develops, which lasts from 2-3 days to 2-3 weeks. In blood anemia, high ESR, azotemia, acidosis, hyperkalemia, in urine - isohypostenuria, hematuria, mononuclear or eosinophilic leukocyturia are revealed. Sometimes there are temperature, chill, skin rashes.

Proteinuria may be of tubular origin (not glomerular); in such cases there is high quantity of β-2-microglobulins, low molecular proteins, because of their low reabsorption in proximal tubules.

The onset of chronic IN is almost asymptomatic; it may be diagnosed by chance when urineanalysis is performed because of different causes. There is no specific picture, but 4 symp-toms are more or less constant: hematuria, dysuria-polyuria, tubular acidosis and “salt-loss” kid-ney. Loss of salts leads to development of muscular and arterial hypotonia, weakness, osteodys-trophy, formation of urolithiasis. Abdominal pains (renal colic), bad appetite, maldigestion may occur. Development of pyelonephritis is a typical outcome of chronic IN; nephrosclerosis with secondary arterial hypertonia, cronic renal failure (CRF) may be seen.

Diagnosis. It is very difficult to diagnose IN as there are abortive forms. ARF (in patients without previous renal lesion) on the ground of ARI, shock, hemolysis, poisoning is very suspi-cious as for IN. Laboratory findings described above help to diagnose IN.

195

Differential diagnosis. It is necessary to differentiate IN from pyelonephritis, diffuse and hereditary glomerulonephritis, renal tuberculosis, tumors, urolithiasis, dysmetabolic nephropathies.

Treatment. This depends on etiology. Abolition of all drugs is necessary. The diet de-pends on peculiarities of renal function and the character of nephropathy. Vitamin A, B6, E, anti-histaminic drugs are administered. In ARF hemodyalisis is of great use. As pathogenetic therapy in acute IN glucocorticoid hormones are necessary, in chronic IN – vitamin A, E, B6, orotic acid, ATA, cocarboxylase, sometimes immunostimulative therapy, phytotherapy, physiotherapy.

TubulopathiesDisorders of tubular functions involve single or multiple transport mechanisms in the

presence of normal glomerular function. They may be congenital or acquired. There are the fol-lowing tubulopathies:

- primary transport defect in reabsorption of one or more specific dissolved substances from glomerular filtrate, e.g. cystinuria or renal glucosuria;

- inability of tubular cells to react to normal hormonal stimulator, e.g. pseudohy-poparathyroidism or nephrogenic diabetes;

- inability to formation or preservation of electric or chemical gradient which permit tubules to fulfil the main specific function, e.g. distal tubular acidosis.

Some tubular disorders are secondary. For example, tubular dysfunction is possible: in systemic diseases because of accumulation of metabolic products such as cystine

crystals in cystinosis or fructose-1-phosphate in congenital fructose intolerance; as a result of action of remedies or toxins, e.g. tubular acidosis after treatment with

amphotericin B or generalized dysfunction of proximal tubules after poisoning with lead (Pb).

Renal glucosuria. Renal glucosuria is an isolated defect of tubular glucose transport, characterized by the presence of glucose in urine at normal blood glucose levels. Glucose metab-olism and other renal tubular transport mechanisms are normal. The abnormal tubular glucose reabsorption consists of a low threshold and a reduced tubular maximum for glucose, or a low threshold and an exaggerated splay but a normal tubular maximum. The disorder is hereditary, asymptomatic and benign.

Cystinuria. The proximal tubular reabsorption of cystine and the diabasic aminoacids or-nithine, lysine and arginine is impaired. Supersaturation of urine with cystine crystals may lead to recurrent calculus formation. Cystine calculi are radioopaque. A large fluid intake, alkaliniza-tion of urine and administration of D-penecillamine will help to prevent calculus formation.

Nephrogenic diabetes insipidus. In this condition, the distal tubules and collecting ducts do not respond to antidiuretic hormone, so that they remain impermeable and there is no passive diffusion of water to equilibrate with the hyperosmolar medulla. Urine is always hypotonic to plasma, except when extreme dehydration is present. In case of infancy failure to thrive, unex-plained fever and dehydration may be significant. These infants are often suspected to have some infection and undergo extensive laboratory investigations. An observant mother may no-tice that the infant continues to pass urine even when dehydrated. Hypernatremia is a character-istic feature. Polyuria and polydipsia are more striking in the older children. Treatment consists of provision of large water intake, sodium restriction and administration of chlorothiazide.

Renal tubular acidosis (RTA). Renal tubular acidosis encompasses a complex group of conditions characterized by a defect of renal acidification, which results in hyperchloremic meta-bolic acidosis and inappropriately high urine pH. The renal function is normal or only slightly reduced. Two main forms are recognized: distal RTA (type 1) and proximal RTA (type 2).

196

Distal renal tubular acidosis. Distal RTA is not uncommon in infants and children. The correct diagnosis is often delayed or missed. The patients have failure of distal urinary acidifica-tion and cannot lower the urine pH below 6. The reduced H+ secretion by the collecting ducts may result from a primary defect of H+ secretory pump or increased cell membrane permeability causing back leak of H+ ions from lumen to cell. The biochemical abnormalities include meta-bolic acidosis, hypokalemia and increased urinary excretion of calcium, sodium and potassium, and decreased urinary citrate. Urinary net acid (titratable acid and ammonia) is markdly reduced. Proximal bicarbonate absorption is characteristically normal in older children but infants may have bicarbonate wasting.

The clinical features include failure to thrive, polyuria and polydipsia, muscular weak-ness, refractory rickets, unexplained fever and episodes of dehydration. Nephrocalcinosis may be detected on ultrasonography for an unrelated problem.

The diagnosis can be made by finding of inappropriate level of urine alkaline during sys-temic acidosis. In incomplete forms of distal RTA or when it is associated with hyperkalemia, detailed laboratory investigations such as measurement of titratable acid after acid loading, de-termining the difference between urine and blood PCO2, can be done.

Treatment. Acidosis can usually be corrected with relatively small doses of alkali, e.g. 3-5 mEq/kg/day, except in infants with bicarbonate wasting. Adequate treatment of acidosis will promote physical growth and heal the rickets. Administration of vitamin D is not necessary. Potassium supplements should be given initially.

Proximal renal tubular acidosis. The capacity of the proximal tubules to reabsorb bicar-bonate is decreased, so that large amounts of bicarbonate are delivered to distal tubules. In com-parison with proximal tubules, distal tubules can only reabsorb much less quantities of bicarbon-ate. Therefore most of the bicarbonate that reaches distal part of nephron is excreted in urine. Consequently as the serum bicarbonate level falls, less quantity of bicarbonate is filtered by the glomeruli till a level is reached, when all the filtered bicarbonate can be reabsorbed by the distal tubules. At that point, the distal nephron can again acidify the urine. The patients loose large amounts of fluid, develop compensatory hyperaldosteronism which causes hypokalemia. The main clinical feature is growth retardation. Rickets and nephrocalcinosis are rare.

Large doses of bicarbonate have been used to correct acidosis but the resulting increase in blood bicarbonate level leads to large urinary losses. Sodium restriction is beneficial since it causes contraction of blood volume and reduces the filtration of bicarbonate. Administration of chlorothiazide has a similar effect.

5.1.6. Acute and Chronic Renal Failure

Acute renal failure (ARF) denotes an acute impairment of renal function, which re-sults in several clinical and biochemical derangements. Anuria or severe oliguria (urine flow less than 300 ml/m2/day or 10-12 ml/kg/day – necessary quantity of urine for excretion of 600 mosmol of osmotic active substances, created during 24 hours in normal diet and metabolism) is the most important feature, although rarely urine output may not be decreased. K.N. Drammond considers that in infants oliguria – it is urine flow less than 180 ml/m2/d, anuria – 60 ml/m2/d (2-3 ml/kg/d), except newborns of first two days when anuria – it is urine flow less than 1 ml/kg/d.

Etiology. Pre-renal, renal and post-renal (obstructive) ARF are marked out.Pre-renal ARF (renal hypoperfusion): hypovolemia and/or hypotension caused by dehy-

dration (vomiting, diarrhea, severe and prolonged fever, decrease of colloid-oncotic blood pres-

197

sure (protein loss in exudative enteropathy, nephrotic syndrome), peritonitis, ascites, burns, sep-tic chock, hemorrhage, congenital heart failure.

Renal:-Acute tubular necrosis: fluid loss, hemorrhage, shock, intravascular hemolysis, sepsis,

nephrotoxic drugs, chemical, radiocontrast media, major surgical procedures, road accidents, ex-tensive burns, hepatic failure, congenital cardiac failure;

-Glomerular disease: acute glomerulonephritis, hemolitic uremic syndrome;-Interstitial nephritis: acute bacterial pyelonephritis, meticillin, sulfonamides;-Miscellaneous: snakebite, renal vein thrombosis;Post-renal (obstructive). Calculi, blood dots, crystals of uric acid, sulfonamides.Pathogenesis. It has been extensively studied in experimental models. Leakage of

glomerular filtrate back into the circulation across the damaged tubular epithelium and tubular obstruction from impaction of proteinaceous casts and cellular debris have been long considered to be responsible for oliguria. The latter may be important in intravascular hemolysis and methe-moglobinuria with renal failure. Glomerular filtration rate (GFR) and renal blood flow are mark reduced, the latter by 50 to 75 percents. The importance of tubular obstruction, back leak of fil-trate and persistent renal vasoconstriction will vary, depending on the cause and duration of re-nal failure. Intense renal vasoconstriction may be caused by increased renin-angiotensis activity which could follow increased delivery of sodium to the macula densa due to proximal tubular dysfunction. Intravascular coagulation may play an important role in cases with sepsis and hemolitic uremic syndrome. Patients with glomerulonephritis and renal failure show severe glomerular lesions, often characterized by extensive crescents.

Ischemic changes consist of focal or patchy necrosis in any part of tubule, but most fre-quently in distal tubules especially at the corticomedullary junction. Proximal tubules are often dilated, but necrosis is uncommon. Nephrotoxic agents cause strong and uniform epithelial dam-age especially in the proximal tubules, without disruption of tubular basement membrane. In post-ischemic injury there is poor correlation between histologic changes and renal functional impairment. Subtle changes in intracellular organelles may be observed by electronmicroscopy in the cells which are not clearly necrotic.

Clinical features. A history of anuria or severe oliguria is present. In a small proportion of cases urine output may not be diminished (“nonoliguric” ARF). Depending upon the underly-ing cause and the duration of renal failure, the child may look remarkably well or extremely sick.

There are 4 phases in ARF: 1) initial(pre-anuric),2) oligo-anuric,3) diuretic,4) convalescence.

In initial phase clinical features of main disease may be seen (1-3 days).Oligo-anuric phase (2-2.5 weeks): decrease of urine output, deterioration of general con-

dition, pallor with jaundice (sometimes hemorrhages on skin, itch), adynamia, headache, weak-ness, nausea, vomiting, diarrhea, tachycardia, decrease of BP, especially diastolic, and after it – hypertension, irregularities of cardiac rhythm and conduction, acidotic breathing, convulsions, abdomen pains, pulmonary edema are seen. Signs of hyperkalemia may be present (muscular weakness, arrhythmia, cardiac arrest), as well as signs of fluid overload (edema of optic papilla, hypertension, cardiac enlargement, gallop rhythm, increase of body weight, pulmonary edema). It is life threatening situation where proper assessment and adequate treatment is highly reward-ing.

198

Diuretic phase (1-6 weeks): urine output starts to increase steadily, general condition im-proves, but hypo-isostenuria, hyponatremia, hypokalemia, hypomagnemia, hypocalcemia, polyuria appear. The patient may get dehydrated if these losses are not adequately replaced. Anemia progresses. Infections are deposited because of depression of humoral and cellular im-munity. Infectious complications are the main cause of death in patients with ARF.

Diagnosis. It is important to detect functional oliguria (“pre-renal type of ARF”) which will rapidly respond to fluid replacement. The bladder should be catheterized to accurately mea-sure the urine output. Increase in urine flow (6 to 10 ml/kg in 1 to 3 hours) is indicative of intact renal function. Determination of ratios of urine and plasma urea and osmolality, and fractional excretion of sodium also help in differentiating functional oliguria from established renal failure. These are based on the impairment of tubular functions in the latter situation, resulting in in-creased sodium excretion in the urine and failure to concentrate the urine. Anemia, elevated ESR, azotemia with concentration of RN more than 72 mmol/l, urea more than 16.7 mmol/l, cre-atinine more than 0.18mmol/l, hyperkalemia more than 6mmol/l, hypocalcemia more than 2 mmol/l, hyperphosphatemia more than 1.8mmol/l, decompensated metabolic acidosis (BE more than 10mmol/l) are typical for ARF.

Treatment. Diet, fluid and electrolytes. It is important to provide sufficient calories to meet nutritional needs. It will also reduce endogenous protein breakdown and thus the metabolic load. Sugar and fat may be freely given. Proteins, sodium and potassium should not be allowed initially. Insensible losses (300 ml/m2/day) should be replaced in the form of water with sugar. This amount should be increased to quantitatively replace the previous 24 hours urine output and any other losses. Administration of calories becomes difficult in presence of vomiting and infu-sion of intravenous glucose may have to be resorted to. The daily vitamin requirement should be given. The child should be accurately weighed daily. With proper management the child should loss about 0.5% of his body weight per day, because of tissue breakdown.

Hyperkalemia. Raised serum potassium level can be temporarily brought down by intra-venous administration of glucose 0.5 g/kg along with soluble insulin 0.1U/kg over a period of 90 min. Calcium antagonizes the cardiotoxicity of hyperkalemia, and intravenous administration of calcium gluconate may be employed for its immediate effect during an emergency (serum potas-sium >8 mEq/l). It should be injected very slowly, the dose being 2.0 ml/kg of a 10% solution over a period of 5 minutes. Persistent hyperkalemia, especially when anuria, infection, hemoly-sis and trauma are present, requires prompt institution of dialysis. Administration of sodium bi-carbonate promptly lowers serum level of potassium by favoring its uptake by the cell; 3 ml/kg of a 7.5% solution of NaHCO3 should be injected.

Metabolic acidosis. Severe acidosis manifested by deep rapid breathing should be treated by administration of sodium bicarbonate, 1 to 2 mEq/kg, the aim being to raise the serum bicar -bonate level to above 15 mEq/l. Since sodium cannot be excreted, it will increase fluid retention and may aggravate hypertension. Persistent acidosis requires dialysis treatment.

Hypertension. Severe hypertension may occur with acute glomerulonephritis and hemolitic uremic syndrome leading to encephalopathy and heart failure. Furosemide 1-2 mg/kg i.v., nifedipine 0.15 mg/kg sublingually may be used. Diazoxid also has a prompt effect and is given as i.v. bolus in a dose of 2 to 5 mg/kg/dose. Hydralasine (0.2mg/kg) may be given i.v. or i.m. and repeated after 3 hours; a precipitous fall of BP may occasionally occur and cause cere-bral or ocular complications. Controlled infusion of sodium nitroprussid with close monitoring of BP is safer in managing hypertensive encephalopathy. After the blood pressure has been brought down, methyldopa or hydralasine may be continued to keep it under control.

General supportive care. The child with acute renal failure should be isolated and man-aged under intensive care conditions. Accurate records of intake and output and daily weight should be maintained. Urine should be collected by condom drainage; bladder should not be

199

catheterized. The risk of infection is very high and appropriate preventive measures should be undertaken. Venipuncture and venisection should be done with strict aseptic precautions. Pro-phylactic antibiotics are not recommended but infections should be detected early and vigorously treated. Their clinical manifestations are often mild and subtle. Sepsis may be indicated by low grade fever, tachycardia and hypotension. Attempts should be made to identify the pathogens, since unusual and opportunistic organisms may be involved. The dosage of antibiotics should be appropriately modified since their excretion is impaired. The total dose or dosing interval or both of these may be varied. The longer the child remains in renal failure, the higher is the inci-dence of infection.

Dialysis. Increasing deterioration of clinical and biochemical status necessitates institu-tion of dialysis. In most cases peritoneal dialysis is the procedure of choice in view of its sim-plicity and easy availability. The need for dialysis should be anticipated. The procedure must be not delayed till the child becomes critically ill. Early dialysis is particularly indicated in the pa-tients with hemolytic uremic syndrome, infections and extensive trauma. The usual guidelines indicating the need for dialysis include: 1) blood urea level of over 250 mg/dL or rapidly rising values; 2) serum potassium higher then 7 mEq/L; 3) serum bicarbonate below 10 mEq/L; 4) overhydration with cardiac embarrassment; 5) sensorial changes or rapid deterioration of neuro-logical status. The decision to dialyze is seldom based on any one criterion, but on careful evalu-ation of all clinical and biochemical data.

Outcome. Acute renal failure still carries a very high mortality, particularly in infants. It is chiefly related to the underlying etiologic condition and the duration of renal failure, which in-creases chances of infection. Septicemia, hemolytic uremic syndrome and glomerulonephritis with prolonged anuria are usually associated with a poor prognosis. The outlook is satisfactory in cases of acute tubular necrosis without complicating factors.

Continuous arteriovenous hemofiltration (CAVH). It is an extracorporeal method for the management of hypervolemia and electrolyte disorders in patients with oliguria. CAVH has been reported to be especially useful in critically ill patients having undergone major surgery and multiorganic failure, who are hemodynamically unstable and where peritoneal dialysis cannot be performed.

Chronic renal failure (CRF) implies permanent, irreversible, severe decrease in re-nal function. This eventually results in end-stage renal disease.

Clinical features and altered physiology. Increased thirst and frequent passage of urine including nocturia are common because of loss of urinary concentrating power. Moderate and at times severe normocytic and normochromic anemia is present. There is bone marrow depression and decrease in iron utilization for hemoglobin synthesis. Erythropoietin production is low mainly because of reduction of functional renal mass. Mild hemolysis and increased loss of blood from gastrointestinal tract also occur.

Growth retardation is a main feature, contributed to by chronic azotemia, anorexia and resultant inadequate nutrition, and bony changes. Skeletal deformities, including rickets and genu valgum may be striking and occasionally present. Osteodystrophy results from a lack of re-nal formation of 1,25(OH)2 D3, malabsorption of calcium and chronic acidosis. The blood pres-sure is increased and the optic fundus shows hypertensive retinopathy.

Systemic acidosis results from severe loss of nephrons with decreased ammonia forma-tion and consequent failure to buffer H+ ions and conserve bicarbonate. Initially it is asympto-matic, but in late stages there may be acidotic breathing, nausea and vomiting. Muscular weak-ness (severe, proximal myopathy may occasionally occur), peripheral neuropathy, itching, pur-pura, pericarditis and infections are late features. Infections are common and may precipitate ter-minal renal failure.

200

It is important to remember that failure to thrive, growth retardation, anemia, hyperten-sion and rickets may occasionally be present in СRF, without there being a clear history of a pre-vious renal disease.

Investigations. The patient should be investigated to find the cause of renal failure and detect reversible factors (e.g., urinary tract obstruction, urinary tract or other infections). Appro-priate imaging studies should be done. Hemogram, serum calcium, phosphate and alkaline phos-phates levels and acid base studies should be obtained. Blood urea and serum creatinine clear-ance should be done. X-ray films of the hands, knees, pelvis and spine should be obtained to document bony abnormalities, and periodically repeated to evaluate the effect of therapy.

Management. Although a cure is not possible, adequate conservative management, pre-vention and treatment of complications can preserve renal function and prolong active life.

I. Diet. Careful attention to details is essential.a) Proteins: The protein intake should be 1g/kg/day, preferably of high biologic value.b) Sodium: The dietary intake of salt should be individualized. Renal regulation of

sodium reabsorption is impaired. Some patients lose large amounts of sodium which can be determined by measuring 24 hours excretion on a fixed sodium intake. Excess sodium will lead to water retention and aggravation of hypertension, whereas a low intake will cause reduction in fluid volume, decreased renal perfusion and increase in azotemia.

c) Potassium: Renal regulation of potassium balance is maintained until very late stages, but the capacity to excrete a rapid potassium load is impaired. Dietary articles with a large potassium content should be avoided.

d) Calcium and phosphorus: Calcium supplements are given in the form of calcium glu-conate or calcium carbonate. Dairy products contain large amounts of phosphates and are restricted.

e) Calories and vitamins. Recommended daily amounts should be given. There is no re-striction of carbohydrates and fats.

f) Water. Liberal water intake should be provided. Dehydration should be quickly cor-rected since it may rapidly cause reduction of renal perfusion and aggravate azotemia.

II. Hypertension. It should be adequately treated to keep the diastolic values below 75-80 mmHg. Hydralasine, propanalol and nifedipine may be used as necessary.

III. Anemia. Iron and folic acid supplements may be given if the blood picture shows hypochromic anemia. Usually the anemia is normocytic and normochromic and results from a deficiency of erythropoietin. The availability of recombinant human erythropoietin has revolu-tionized the management of anemia in chronic renal failure. With its administration, satisfactory levels of hemoglobin and hematocrit can be maintained. The drug, however, is very expensive. If the hemoglobin level falls below 6 g/dL, small packed cell transfusions may be given to in-crease the level to 8-9 g/dL. Blood should be transfused very slowly, under careful supervision, since it may occasionally aggravate hypertension and precipitate heart failure.

IV. Infections. Urinary tract infections and other infections should be promptly treated with effective and least toxic drugs. The dosage of drags should be modified (reduction of dosage or increase in dosing interval or both of these measures), depending upon the serum crea-tinine levels or the creatinine clearance.

V. Growth. Administration of recombinant human growth hormone has been shown to increase the rate of growth in children with chronic renal failure.

VI. Renal (azotemic) osteodystrophy. Azotemic osteodystrophy is a more serious prob-lem in children as it occurs during the period of growth. Its prevention and adequate treatment are crucial, the lack of which may result in crippling deformities and incapacitation. The proxi-

201

mal nephron is the chief site of synthesis of calcitriol, the most potent metabolite of vitamin D. Its deceased productions is an important factor in the pathogenesis of secondary hyperparathy-roidism in CRF. During reduction of renal function, phosphate balance is initially maintained by its increased excretion from the remaining normal nephrons. However, when the GFR falls be-low 25% blood phosphate levels rise.

Clinical features. Initially the symptoms are vague and nonspecific. Bone pains and mus-cular weakness may be present. Growth retardation and later skeletal deformities such as genu valgum are marked. Other features of rickets are present.

Investigation. Blood examination shows hypocalcemia, hyperphosphatemia and raised levels of alkaline phosphatase and parathormone. Radiological abnormalities include metaphy-seal changes suggestive of rickets. Features of secondary hyperparathyroidism such as bone re-sorption, typically seen in the phalanges, clavicles, ischium, pubis and sacroiliac joints may be visible. The skull may show ground glass appearance, mottling and focal sclerosis.

Management. The treatment is based on dietary restriction of phosphate and administra-tion of phosphate binders and vitamin D. When GRF is reduced below 50%, phosphate contain-ing dietary articles (mostly dairy products) should be curtailed. Calcium carbonate or calcium acetate should be used to reduce intestinal absorption of phosphate. These are given in a dose of 0.5-1 g/day with meals. Aluminum salts are not used as aluminum may cause bone disease. Blood phosphate levels should be maintained in the normal range and hypophosphatemia avoided. Vitamin D analogs with short half life are preferable. Calcitriol 20-60 ng/kg/day or standard vitamin D in large doses (10 000-50 000 U/day) may be used. Hypercalcemia and hy-percalciuria should be avoided otherwise renal damage may be aggravated. Orthopedic treatment may be required to correct deformities of lower extremities.

VII. Long term care. The rate of progression of chronic renal injury is very variable. In some disorders (e.g, hemolytic uremic syndrome, crescentic glomerulonephritis) the final stage of a renal disease may develop within a few weeks or months. In several other conditions, partic-ularly reflux nephropathy and some forms of glomerulonephritis, the rate of deterioration of re-nal function may be very slow lasting over a period of several years.

A rapid deterioration in renal function indicates a search for a reversible complication (infection, fluid loss, hypertension, use of nephrotoxic drug). Eventually, however, the final stage of a renal disease necessitates some form of renal replacement therapy.

Optimal management of chronic renal failure involves a team approach including pedi-atric nephrologist, trained nurse, dietitian, social worker and orthopedic surgeon. Every attempt should be made to keep the child ambulatory and let him carry out his usual activity. Constant encouragement and emotional support are necessary.

Chronic dialysis. Appropriate dialysis catheters and dialysis bags are now available. Chronic dialysis, peritoneal or hemodialysis, should be undertaken when renal transplantation is an option. The socioeconomic factors should always be taken into account.

Renal transplantation. The feasibility and efficacy of renal transplantation in children has been well established.

In economically advanced countries the procedure is employed as standard therapeutic modality for children with the final stage of a renal disease. Successful renal transplants have been carried out even in infants. With advances in surgical skills, technical problems have become rare. The immunosuppressive management is now safer and more effective with the use of antilymphocyte globulin and cyclosporin A, and that of acute rejection of OKT3. Renal transplantation requires teamwork and long-term supervision. The procedure should be employed in carefully selected cases at centers where adult transplant services are well established.

202

5.2. Practical skills which are necessary for students of IV course of medical faculty

NN Practical skills Practicallesson

Level ofmaster-ing

AttestationPass-examina-tion

Exam

theoretical practical

1 2 3 4 5 6 7

1. To be able to prescribe diet for a child with malnutrition

N4 (malnutri-tion)

A N1 + +

2. To calculate dose of vit D fora) treatment and b) prevention of rickets

N3(hypovita-minoses, rick-ets)

A N 1 + +

N4 A N1 +

3. To be able to render first aid in tetany

N3 A N1 +

4. To be able to render first aid inconvulsions in children

N3 A N1 +

5. To be able to render first aid inhypervitaminosis D in children

N3 A N1 +

6. To be able to render first aid inneuro-toxicosis (infectious - toxic shock) in children

N7(Acute pneu-monias)

A N2 +

7. To calculate necessary volumeof infusion solutions for correction of water- electrolyte disorders inintestinal toxicosis of differentdegrees (as a variant of infectious-toxic shock)

N5(Acute disor-ders of diges-tion)

A N1 +

8. To be able to evaluate the resultsof general analyses of:a) bloodb) urinec) stoold) samples for activity of inflam

matory process in somatic dis-eases in children

NN2-6 A N1N1N1

+++

+++

9. To be able to evaluate the results of X- ray of chest in pneumonias and their complications

N6,7,8 A N2 + +

10. To be able to prescribe measures of N7 A N2 + +

236

rehabilitation for children with so somatic pathology of respiratory tract

11. To be able to render first aid in hy-pertermia in children

N7 A N2 +

12. To be able to render first aid in res-piratory insufficiency

NN6,7,8 A N2 +

13. To be able to render first aid in asthmatic status

NN6,7,8 A N2 +

14. Carrying out of oxygen therapy NN6,7,8 A N2 +

15. Liquidation of valvular pneumo- thorax

N7 B N2 +

16. Carrying out of pleural punction in children

N7 B N2 +

17. To be able to define activity of rheumatic process

N9 A N2 +

18. To be able to calculate the thera-peutic and saturation dose of heart glycozides

N9 A N2 +

19. To be able to render first aid in short wind cyanotic attack

N9 A N2 +

20. To be able to render first aid in pul-monary edema

NN 6,7,8 A N2 +

21. To be able to render first aid in at-tack of paroxismal tachycardia

N9 A N2 +

22. To be able to prescribe course of treatment with iron in children with anemia

N3 A N2 +

23. To be able to render first aid in gas-trointestinal hemorrhage as a com-plication of gastric ulcer

N10 A N2 +

24. To be able to render first aid in vomiting syndrome in children

N13 A N2 +

25. To be able to render first aid in acute vessels insufficiency in chil-dren(syncope, swoon)

N9 A N2 +

26. To be able to make up properly the case history of a child who stays in hospital, on discharge, to fill in a list of prescription

N1 A N1 + +

27. To be able to evaluate the gravity of patient's condition

N1 A N1 + +

237

5.3. List of drugs1. Ergocalciferol2. Calcium Gluconas3. Calcium Chloride4. Diazepam ( Sibazonum, Seduxen, Re-

lanium)5. Natrii Oxybutyras ( Oxybutyrate

Sodium)6. Diphenhydraminum (Dimedrolum)7. Chloropyraminum ( Suprastinum)8. Clemastinum ( Tavegyl)9. Loratadinum ( Claritin)10. Cetitizinum 11. Allopurinolum12. Riboflavin13. Domperidonum (motilium)14. Loperamid15. Smecta (Diosmetium)16. Chloramphenicolum17. Festal18. Mesym-forte19. Kreon (Pancreatinum) 20. Linex21. Thiamine ( Thiamini Bromidi) 22. Pyridoxine ( Pyridoxini hydrochlo-

ridum)23. Interferonum alfa24. Analgin25. Aspirin26. Paracetamol27. Aminophyllinum28. Acetylcysteinum29. Ambroxolum30. Benzylpenicillinum31. Amoxicillinum32. Augmentin33. Cefasolinum34. Cefuroximum35. Ceftriaxon36. Cefotaximum37. Ciprofloxacinum38. Azitromycinum39. Spiramycinum 40. Erytromycinum41. Amicacinum42. Gentamicinum43. Acidum Ascorbinicum44. Cocarboxilazum45. Hyaluronidasum

46. Ribomunil47. Tylede (Nedochromil)48. Acidum chromoglicum (Intal)49. Salbutamol50. Fenoterolum51. Prednisolonum52. Beclometasonum53. Ketotifenum54. Bicilin 1,3,555. Potassium choridis56. Panangin57. ATA58. Verapamilum59. Sthrophantinum60. Digoxinum61. Almagel62. Bismuthi Subcitras (De-nol)63. Ranitidinum64. Omeprazolum65. Metronidasol66. Drotaverinum67. Magnesii sulfas68. Essentiale69. Silimarin70. Contrical71. Dextrosum72. Natrii chloridum73. Enalaprilum74. Curantyl (Dipiridamolum)75. Dimephosphonum76. Tocopheroli Acetas77. Cyclophosphamidum78. Chlorambucilum79. Nifedipinum80. Chloroquinum81. Furocemidum82. Co-trimoxazolum83. Furazidinum

239

5.4. List of Test questions. 1. The main principles of organization of health care for children in Ukraine. Recent advances in pediatric diagnosis. Indices of the activity of the medical institutions: infant mortality, total mortality in childhood.2. Ethics in pediatric care. Medical mistakes in pediatrics.3. Constitution’s anomalies. Etiology. Pathogenesis. Age peculiarities of the clinic. Treatment and prevention.4. Atopic diathesis. Diagnosis, clinical picture and treatment. Infantile eczema. Clinical manifes-tations. Treatment.5. Classification of acute disorders of gastro-intestinal tract in infants. Dyspepsia simplex. Eti-ology, pathogenesis, clinics. Treatment, prevention.6. Immunodeficiencies in childhood. Main clinical forms. Principles of treatment.7. Malabsorbtion syndrome in childhood. Clinical manifestations of cystic fibrosis. Principles of treatment.8. Rickets. Etiology, pathogenesis, classification, clinical manifestations.9. Treatment of rickets, prevention.10. Hypervitaminosis D. Diagnosis, clinics, urgent help, prevention.11. Hereditary tubular disorders in childhood. Differential diagnosis with rickets.12. Tetany in rickets. Clinical manifestations, diagnosis and treatment.13. Differential diagnosis of convulsions in childhood. Principles of urgent help.14.Chronic nutritional disorders. Classification. Clinical manifestations of hypotrophy. Paratro-phy. Treatment and prevention.15. Treatment of chronic nutritional disorders depending on etiology and degree of gravity. Pe-culiarities of diet therapy.16. Intestinal toxicosis with dehydration. Symptoms of dehydration in dependence on it’s sever-ity.17. Diet therapy of the intestinal toxicosis. Antibiotic, symptomatic treatment. Peculiarities of infusion therapy in dependence on degree of dehydration. Oral rehydration therapy.18. Neurotoxicosis. Etiology, pathogenesis. Urgent help.19. Disbacteriosis in childhood.20. Acute respiratory disorders in childhood. Clinical forms.21. Bronchitis in childhood. Classification. Clinical forms. Bronchiolitis. Antiviral treatment.22. Spasmodic crup in childhood. Urgent help.23. Acute pneumonia. Etiology. Pathogenesis. Classification. Clinical forms.24. Pneumonia in childhood. Clinics, diagnosis. Differential diagnosis. Peculiarities of clinical forms in dependence on etiology.25. Clinical manifestations of segmental and polysegmental pneumonia. Roentgenografic find-ings. Antibiotic, desintoxicative treatment and immunotherapy.26. Interstitial pneumonia in childhood. Clinical manifestations. Diagnosis. Treatment.Complications of pneumonia (pleuritis, pneumothorax). Clinical manifestations. Diagnosis. Treatment.28. Staphylococcal pneumonia in infants. Clinical manifestations. Diagnosis. Treatment.29. Staphylococcal destruction of lungs: abscess, empyema, and pneumothorax. Urgent help.30. Main clinical symptoms of the complications of pneumonia. Treatment of cardio-pulmonary insufficiency in childhood. Urgent help.31. Principles of the complex treatment of acute pneumonia. Aerotherapy, antibiotic treatment and immunotherapy. Physiotherapy.32. Syndromal treatment of acute pneumonia in childhood.33. Clinical-roentgenografic peculiarities of the staphylococcal destruction of lungs ( abscess, bulla, pleural complications). Urgent help. Indications for drainage.34. Chronic bronchitis. Clinical variants. Diagnosis. Differential diagnosis with cystic fibrosis.

241

35. Acute obstructive bronchitis and recurrent bronchitis. Clinical manifestations. Diagnosis. Treatment. Physiotherapy.36. Pulmonary insufficiency in childhood. Classification. Clinical manifestations. Treatment.37. Treatment of chronic bronchitis. Aerotherapy. Rational antibiotic and hormone treatment. Immunotherapy. Physiotherapy. Therapeutic bronchoscopy.38. Allergic disorders of the respiratory system in childhood. Classification. Clinical forms.39. Bronchial asthma. Etiology and pathogenesis. Immune and nonimmune forms. Asthma of exertion.40. Differential diagnosis between forms of bronchial asthma. Clinical manifestations of status asthmaticus.41. Urgent help for children with status asthmaticus. Bronchodilators medication. Therapeutic bronchoscopy.42. Treatment of bronchial asthma in acute phase. Urgent help in status asthmaticus and dysp-nea. Indications for mechanical ventilation.43. Treatment of bronchial asthma in remission phase.44. Rheumatic fever in childhood. Clinical forms. Peculiarities of course of rheumatic fever de-pending on age.45. Rheumatic fever. Criteria for diagnosis. Classification. Diagnosis of endocarditis.46. Carditis in rheumatic fever. Clinical manifestations. Diagnosis. Differential diagnosis with other carditis.47. Noncardial manifestations of rheumatic fever. Diagnosis. Differential diagnosis with rheumatoid arthritis. Treatment.48. Treatment of rheumatic fever. Indications for tonsillectomy.49. Primary and secondary prophylaxis of rheumatic fever.50. Acquired heart defects. Clinical variants. Modern methods of diagnosis.51. Acquired aortic defects. Aortic stenosis and insufficiency. Peculiarities of blood circulation. Clinical manifestations.52. Acquired mitral defects. Mitral stenosis. Insufficiency of mitral valve. Mitral disease. Pecu-liarities of blood circulation. Clinical manifestations.53. Acute heart failure. Clinics. Treatment.54. Chronic heart failure. Clinics. Treatment. Methods of digitalization.55. Nonrheumatic carditis in childhood. Diagnosis. Clinical manifestations. Treatment.56. Cardiomyopathies in childhood. Peculiarities of clinical manifestations.57. Clinical variants of rheumatic fever. Rheumatic chorea. Differential diagnosis with hyperky-nesias. Treatment.58. Methods of determination of rheumatic fever activity.59. Congenital heart and magistral vessels diseases. Classification. Phases of the adaptation of blood circulation in congenital heart diseases. Conservative treatment of congenital heart dis-eases. Methods of digitalization.60. Acyanotic congenital heart diseases. Clinical forms. Peculiarities of blood circulation.61. Atrioventricular septal defect and ventricular septal defect. Disturbance of blood circulation. Indications for surgical treatment.62. Congenital heart diseases with decreased pulmonary blood flow. Clinical forms.63. Tetralogy of Fallot. Disturbance of blood circulation. Clinical manifestations. Treatment.64. Urgent help for patients with paroxismal hypercyanotic attacks.65. Aortic stenosis. Coarctation of the aorta. Clinical manifestations. Treatment. Indications for surgical treatment.66. Acute and chronic gastritis. Peculiarities of clinical manifestations.67. Peptic ulcer disease in children. Clinical manifestations. Treatment. Prophylaxis.68. Acute and chronic gastritis. Etiology, clinics, treatment. Physiotherapy.

242

69. Gastroduodenitis and duodenitis in childhood. Methods of diagnosis of functions of stomach and duodenum. Main medicaments for treatment.70. Peptic ulcer disease in children. Peculiarities of clinical manifestations depending on age. Diagnosis. Treatment. Diet therapy.71. Chronic disorders of liver and biliary system. Dysfunction of biliary system. Clinical vari-ants. Treatment. Physiotherapy.72. Cholecystitis and cholangitis in childhood. Etiology, pathogenesis. Clinical manifestations. Treatment. Physiotherapy.73. Cholecystitis. Lambliosis. Diagnosis. Clinical manifestations. Treatment.74. Cholelithiasis in children. Diagnosis. Clinical manifestations. Treatment.75. Prophylactic system for patients with disorders of liver and biliary system. Peculiarities of diet. Sanatorium treatment.76. Pancreatitis in childhood. Etiology, pathogenesis. Classification. Clinical forms. Treatment.77. Chronic pancreatitis in children. Peculiarities of clinical manifestations and treatment. 78. Chronic hepatitis in childhood. Diagnosis. Clinical manifestations. Treatment.79. Hepatic cirrhosis. Diagnosis. Clinical manifestations. Treatment.80. Ascariasis in childhood. Diagnosis. Clinical manifestations. Treatment. Prevention.81. Enterobiasis. Diagnosis. Clinical manifestations. Treatment.82. Trichuriasis. Diagnosis. Clinical manifestations. Treatment.83. Classification of kidney diseases. Methods of diagnosing of kidney diseases.84. Acute glomerulonephritis in children. Etiology, pathogenesis. Classification. Clinical forms. Treatment.85. Differential diagnosis between acute glomerulonephritis and kidney infection.86. Acute and chronic renal failure. Treatment. Indications for hemodialysis.87. Treatment of acute glomerulonephritis. Peculiarities of diet therapy. Prevention.88. Pathogenesis of edema, anemia and hypertension in acute glomerulonephritis. Treatment.89. Chronic glomerulonephritis. Etiology, pathogenesis. Classification. Clinics. Complications.90. Principles of treatment of chronic glomerulonephritis depending on clinical form and phase of disease.91. Hereditary nephritis ( Alport syndrome).92. Nephrotic syndrome in childhood. Clinical manifestations. Treatment.93. Urinary tract infections in childhood. Classification. Etiology, pathogenesis. Clinics. Com-plications.94. Cystitis in children. Diagnosis. Clinical manifestations. Treatment. Physiotherapeutic meth-ods of treatment.95. Acute pyelonephritis in children. Etiology, pathogenesis. Classification. Primary and sec-ondary pyelonephritis. Clinical forms.96. Diagnosis of acute pyelonephritis. Differential diagnosis.97. Treatment of acute pyelonephritis. Diet therapy. Peculiarities of antibiotics treatment. Phys-iotherapeutic methods of treatment.98. Chronic pyelonephritis in children. Etiology, pathogenesis. Classification. Clinics. Compli-cations.99. Pylorostenosis and pylorospasm. Diagnosis and treatment.100. Anemia due to iron or vitamin deficiency. Diagnosis and treatment.101. Disorders of esophagus. Clinical manifestations. Treatment.102. Dysmetabolic nephropathies in children. Clinical manifestations. Treatment.103. Acute vascular insufficiency in children ( shock, swoon, collapse).104. Sanatorium treatment of patients with cardiovascular pathology.105. Sanatorium treatment of patients with gastro-intestinal pathology.106. Sanatorium treatment of patients with renal pathology.107. Sanatorium treatment of patients with respiratory tract pathology.

243

108. Rehabilitation of children after diseases of cardio respiratory system, gastro-intestinal tract, renal system.109. Medical prophylactic system for children.110. Groups of health in children.111. Acute disorders of gastro-intestinal tract in infants. Simple dyspepsia. Etiology, pathogene-sis. Clinics. Complications.112. Respiratory viral infections in children. Antiviral treatment.113. Obstructive bronchitis in children. Treatment. Physiotherapeutic methods of treatment.

244