NUTRITIONAL DISORDERS I

1. NUTRITIONAL DISORDERS I Myrna D.C. San Pedro, MD, FPPS

2. MALNUTRITION A pathological state resulting from a relative or absolute deficiency or excess of one or more essential nutrients; clinically manifested or detected only by biochemical, anthropometric or physiological tests.

3. Forms of Malnutrition • Undernutrition: Marasmus • Overnutrition: Obesity, Hypervitaminoses • Specific Deficiency: Kwashiorkor, Hypovitaminoses, Mineral Deficiencies • Imbalance: Electrolyte Imbalance

4. ETIOLOGY

7. Classification of Undernutrition • Gomez Classification: uses weight-for-age measurements; provide grading as to prognosis Weight-for-Age%Status 91-100 Normal 76-90 1st degree 61-75 2nd degree <60 3rd degree

8. Wellcome Classification: simple since based on 2 criteria only - wt loss in terms of wt for age% & presence or absence of edema Wt-for-Age%EdemaNo Edema 80-60 Kwashiorkor Undernutrition < 60 Marasmic- Marasmus Kwashiorkor

9. Waterlow Classification: adopted by WHO; can distinguish between deficits of weight-for-height% (wasting) & height-for-age% (stunting) NMildModSevere Ht-for-Age% >95 90-95 80-90 <80 Wt-for-Ht% >90 80-89 70-79 <70

10. Protein Energy Malnutrition Iceberg

11. Marasmus • Common in the 1st year of life Etiology: • “Balanced starvation” • Insufficient breastmilk • Dilute milk mixture or lack of hygiene

12. Clinical Manifestations: Wasting Muscle wasting Growth retardation Mental changes No edema Variable-subnormal temp, slow PR, good appetite, often w/diarrhea, etc. Laboratory Data: Serum albumin N Urinary urea/ gm crea N Urinary hydroxyproline/ gm crea low, early Serum essential a.a. index N Anemia uncommon Glucose tolerance curves diabetic type K+ deficiency present Serum cholesterol low Diminished enzyme activity Bone growth delayed Liver biopsy N or atrophic Marasmus

13. Kwashiorkor • Between 1-3 yrs old Etiology: • Very low protein but w/calories from CHO • In places where starchy foods are main staple • Never exclusively dietary

14. Clinical Manifestations: Diagnostic Signs Edema Muscle wasting Psychomotor changes Common Signs Hair changes Diffuse depigmentation of skin Moonface Anemia Occasional Signs: Flaky-paint rash Noma Hepatomegaly Associated Laboratory: Decreased serum albumin EEG abnomalities Iron & folic acid deficiencies Liver biopsy fatty or fibrosis may occur Kwashiorkor

15. Kwashiorkor

16. Treatment of PEM • Severe PEM is an emergency, hospitalization 1-3 mo desirable • On admission, treat vitamin deficiencies, dehydration & associated infections • In the acute phase, feeding started as soon as rehydrated & when edema is lost, full-strength feeds given with maintenance calories & protein; recovery after 2-3 wks • Rehabilitation with high energy feeds (150-200 kcal/kg/day) started once full-strength feeds tolerated; recovery expected within 4-6 wks on high energy feeds

17. Prognosis of PEM • Permanent impairment of physical & mental growth if severe & occurs early especially before 6 months old • First 48 hours critical, with poor treatment mortality may exceed 50% • Even with thorough treatment, 10% mortality may still occur • Some mortality causes are endocrine, cardiac or liver failure, electrolyte imbalance, hypoglycemia & hypothermia

18. Obesity • Definition: Generalized, excessive accumulation of fat in subcutaneous & other tissues • Classification according to “desirable” weight standard: Overweight ~ >10% while Obese ~ >20% • The Centers for Disease Control (CDC) avoids using "obesity" instead suggest two levels of overweight: 85th percentile of BMI ~ "at risk" level & 95th percentile of BMI ~ the more severe level • The American Obesity Association uses: The 85th percentile of BMI for overweight because ~ BMI of 25, overweight for adults and the 95th percentile of BMI for obesity because ~ BMI of 30, the marker for obesity in adults

19. Obesity • Appears most frequently in the 1st year, 5-6 years & adolescence Etiology: • Excessive intake of food compared w/ utilization • Genetic constitution • Psychic disturbance • Endocrine & metabolic disturbances rare • Insufficient exercise or lack of activity

20. Obesity Clinical Manifestations: • Fine facial features on a heavy-looking taller child • Larger upper arms & thighs • Genu valgum common • Relatively small hands & fingers tapering • Adiposity in mammary regions • Pendulous abdomen w/ striae • In boys, external genitalia appear small though actually average in size • In girls, external genitalia normal & menarche not delayed • Psychologic disturbances common • Bone age advanced

21. Obesity

22. Treatment of Obesity • 1st principle: decrease energy intake • Initial med exam to R/O pathological causes • 3-day food recall to itemize child’s diet • Plan the right diet • Avoid all sweets, fried foods & fats • Limit milk intake to not >2 glasses/day • For 10-14 yrs, limit to 1,100-1300 cal diet for several months • Child must be properly motivated & family involvement essential • 2nd principle: increase energy output • Obtain an activity history • Increase physical activity • Involve in hobbies to prevent boredom

23. Complication of Obesity Pickwickian Syndrome • Rare complication of extreme exogenous obesity • Severe cardiorespiratory distress & alveolar hypoventilation • Includes polycythemia, hypoxemia, cyanosis, CHF & somnolence • High O2 conc dangerous in cyanosis • Weight reduction ASAP & quick

24. The Energy-Releasing Vitamins

25. Typical symptoms for the group include: Dermatitis Glossitis Cheilitis Diarrhea Nerve cells use lots of energy, so symptoms also show up in the nervous tissue: Peripheral neuropathy Depression Mental confusion Lack of motor coordination Malaise Thiamine, Riboflavin, Niacin, Pyridoxineare cofactors to enzymes in energy metabolism, hence, deficiencies show up in quickly growing tissues such as epithelium.

26. Thiamine (Vitamin B1) Deficiency Beriberi Pathology: Biochemically, there is accumulation of pyruvic and lactic acid in body fluids causing: • Cardiac dysfunction such as cardiac enlargement esp right side, edema of interstitial tissue & fatty degeneration of myocardium • Degeneration of myelin & of axon cylinders resulting in peripheral neuropathy and • In chronic deficiency states, vascular dilatation & brain hemorrhages of Wernicke’s Disease, resulting in weakness of eye movement, ataxia of gait and mental disturbance

27. Thiamine Deficiency (Beriberi) Three forms: • Wet beriberi: generalized edema, acute cardiac symptoms and prompt response to thiamine administration • Dry beriberi: edema not present, condition similar to peripheral neuritis w/ neurological disorders present • Infantile beriberi divided into: • Acute cardiac - ages 2-4 months; sudden onset of cardiac s/sx such as cyanosis, dyspnea, systolic murmur & pulmonary edema w/ rales • Aphonic - ages 5-7 months; insidious onset of hoarseness, dysphonia or aphonia • Pseudomeningeal - ages 8-10 months; signs of meningeal irritation w/ apathy, drowsiness & even unconsciousness; occurs more often

28. Diagnosis: Clinical manifestations not conclusive Therapeutic test w/ parenteral thiamine = dramatic improvement Blood lactic & pyruvic acid levels elevated after oral load of glucose Decreased red cell hemolysate transketolase RDA: Infants 0.4mg Older children 0.6-1.2mg Nursing mothers 1.5mg Adults 1-1.3mg Prevention: Richest sources are pork, whole grain, enriched cereal grains and legumes Improved milling of rice conserve thiamine Excessive cooking of vegetables or polishing of cereals destroy In breast-fed infants, prevention achieved by maternal diet w/ sufficient amounts Treatment: Children: 10mg p. o. daily for several weeks Adults 50mg Thiamine Deficiency (Beriberi)

29. Thiamine Deficiency (Beriberi)

30. Thiamine Deficiency (Beriberi)

31. Riboflavin (Vitamin B2) Deficiency Functions: • Acts as coenzyme of flavoprotein important in a. a., f. a. & CHO metabolism & cellular respiration • Needed also by retinal eye pigments for light adaptation Clinical Manifestations: • Characteristic lesions of the lips, the most common of which are angular stomatitis and cheilosis • Localized seborrheic dermatitis of the face may result such as nasolabial seborrhea or dyssebacia and angular palpebritis • Scrotal or vulvar dermatosis may also occur • Ocular s/sx are photophobia, blurred vision, itching of the eyes, lacrimation & corneal vascularization

32. Riboflavin Deficiency Diagnosis: • Urinary riboflavin determination • RBC riboflavin load test RDA: Infants & children <10yrs 0.6-1.4mg Children >10yrs 1.4-2mg depending on food intake Adults 0.025mg/gm dietary protein Prevention: • Best sources: eggs, liver, meat, fish, milk, whole or enriched ground cereals, legumes, green leafy vegetables • Also present in beer • Impaired absorption in achlorhydria, diarrhea & vomiting Treatment: • Riboflavin 2-5mg p. o. daily w/ increased B complex • Parenteral administration if relief not obtained

33. Riboflavin Deficiency

34. Niacin (Vitamin B3) Deficiency Pellagra Etiology: • Diets low in niacin &/or tryptophan • Amino acid imbalance or as a result of malabsorption • Excessive corn consumption Clinical Manifestations: • Start w/ anorexia, weakness, irritability, numbness & dizziness • Classical triad of dermatitis, diarrhea & dementia • Dermatitis may develop insidiously to sunlight or heat • First appears as symmetrical erythema • Followed by drying, scaling & pigmentation w/ vesicles & bullae at times • Predilection for back of hands, wrists, forearms (pellagrous glove), neck (Casal’s necklace) & lower legs (pellagrous boot) • GIT s/sx are diarrhea, stomatitis or glossitis; feces pale, foul milky, soapy or at times steatorrheic • Mental changes include depression, irritability, disorientation, insomnia & delirium

35. Niacin Deficiency (Pellagra) Diagnosis: • History & manifestations of diet poor in niacin or tryptophan • In niacin deficiency, urinary levels of N-methyl-nicotinamide low or absent Differential diagnoses: Kwashiorkor, Infantile Eczema, Combination deficiencies of amino acids & trace minerals such as zinc RDA: Infants & children <10yrs 6-10mg Older individuals 10-20mg Prevention: • Rich sources include meat, peanuts and legumes, whole grain and enriched breads and cereals • Avoid too large a proportion of corn Treatment: • Niacin 50-300mg daily which may be taken for a long time • Skin lesions may be covered w/ soothing lotions

36. Niacin Deficiency (Pellagra)

37. Pyridoxine (Vitamin B6) Deficiency Functions: • Vitamin B6 is involved in the synthesis and catabolism of amino acids, synthesis of neurotransmitters, porphyrins and niacin • Plays important role in clinical conditions such as anemia, hyperemesis gravidarum, cardiac decompensation, radiation effects, skin grafting, INH therapy & seborrheic dermatitis Etiology: • Losses from refining, processing, cooking & storing • Malabsorptive diseases such as celiac disease may contribute • Direct antagonism might occur between INH & pyridoxal phosphate at the apoenzyme level

38. Pyridoxine Deficiency Clinical Manifestations: • Three different types • Neuropathic, due to insufficient neurotransmitter synthesis, such as irritability, depression & somnolence • Pellagrous, due to low endogenous niacin synthesis, such as seborrheic dermatitis, intertrigo, angular stomatitis & glossitis • Anemic, due to low porphyrin synthesis, such as microcytic anemia & lymphopenia • In genetic diseases involving pyridoxal phosphate enzymes also xanthurenic aciduria, cystathioninuria & homocystinuria

39. Pyridoxine Deficiency Diagnosis: As screening test, tryptophan load test done -100mg/kg BW tryptophan will give large amount of xanthurenic acid in urine Prevention: • Firm requirement not established but usually recommended: Infant 0.1-0.5mg, Child 0.5-1.5mg & Adult 1.5-2mg • Rich sources include yeast, whole wheat, corn, egg yolk, liver and lean meat • Toxicity at extremely high doses has been described; infants whose mothers received large doses during pregnancy should be observed for seizures due to dependency • Children receiving INH therapy should be observed for neurologic s/sx in w/c case pyridoxine should be given Treatment: • Pyridoxine 100mg IM injection for seizures due to deficiency • Children w/ pyridoxine dependency should be given 2-10mg IM injection or 10-100mg oral vitamin B6

40. The Hematopoietic Vitamins

41. Functions: Needed for RBC & DNA formation, cell multiplication esp. GI cells Newly discovered functions: Prevents neural tube defects Prevents heart disease (reduces homocysteine levels) Prevents colon cancer Etiology: Peak incidence 4-7 months Deficient dietary intake: goat’s milk deficient & powdered milk poor source Deficient absorption as in celiac disease, achlorhydria, anticonvulsant drugs, zinc deficiency & bacterial overgrowth Impaired metabolism w/ ascorbic acid deficiency, hypothyroidism, drugs like trimethoprim & alcoholism Increased requirement during rapid growth & infection Increased excretion/loss may occur subsequent to vitamin B12 deficiency & chronic alcoholism Increased destruction possible in cigarette smoking Folic Acid (Vitamin B9) Deficiency

42. Clinical Manifestations: Megaloblastic anemia w/ irritability, failure to gain wt & chronic diarrhea Thrombocytopenic hemorrhages advanced cases Scurvy may be present Laboratory Findings: Anemia macrocytic Serum folic acid <3ng/ml, normal level=5-20ng/ml RBC folate levels indicator of chronic deficiency, normal level=150-600ng/ml Serum iron & vitamin B12 normal or elevated Formiminoglutamic acid in urine esp after oral histidine Serum LDH markedly high Bone marrow hypercellular RDA: 20-50mcg/24 hrs Treatment: Parenteral folic acid 2-5mg/24 hrs, response in 72 hrs, therapy for 3-4 wks Transfusions only when anemia severe Satisfactory responses even w/ low doses of 50mcg/24 hrs, have no effect on primary vitamin B12 deficiency If pernicious anemia present, prolonged use of folic acid should be avoided Folic Acid Deficiency

43. Folic Acid Deficiency

44. Cobalamine (Vitamin B12) Deficiency Absorption: Vitamin B12 + glycoprotein (intrinsic factor) from parietal cells of gastric fundus  terminal ileum absorption + intrinsic factor + Ca++  blood Function: Needed in reactions affecting production of methyl groups Etiology: • Congenital Pernicious Anemia: Lack of secretion of intrinsic factor by stomach manifest at 9 months-10 years as uterine stores become exhausted • Inadequate intake or dietary deficiency rare • Strict vegetarian diet • Not commonly seen in kwashiorkor or marasmus • Breast-fed infants whose mothers had deficient diets or pernicious anemia • Consumption or inhibition of the B12-intrinsic factor complex • Vitamin B12 malabsorption from disease of ileal receptor sites or other intestinal causes

45. Cobalamine Deficiency Clinical Manifestations: • Megaloblastic anemia that becomes severe • Neurological includes ataxia, paresthesias, hyporeflexia, Babinski responses, clonus & coma • Tongue smooth, red & painful Laboratory Findings: • Anemia macrocytic • Serum vitamin B12 <100pg/ml but serum iron & folic acid normal or elevated • Serum LDH activity markedly increased • Urinary excess of methylmalonic acid, a reliable & sensitive index

46. Cobalamine Deficiency • Schilling test to assess the absorption of vitamin B12: • Normal person ingests small amount of radioactive vitamin B12  none in urine **If flushing dose injected parenterally, 1000mcg of non-radioactive vitamin B12  10-30% of previous radioactive vitamin B12 appears in the urine • Pernicious anemia  2% or less **If modified: 30 mg intrinsic factor administered along  normal amounts • Disease of ileal receptor sites or other intestinal causes  no improvement even w/ intrinsic factor RDA: Infants 0.5 mcg/day Older children & adults 3mcg/day Treatment: • Prompt hematological response w/ parenteral vitamin B12 1-5mcg/24hrs • If there is neurological involvement 1mg IM daily for at least 2wks • Pernicious Anemia: Monthly vitamin B12 1mg IM necessary throughout patient’s life

47. Cobalamine Deficiency

48. Ascorbic Acid (Vitamin C) Deficiency Scurvy Functions: • Collagen is the major connective tissue in the body & hydroxyproline, found only in collagen, is formed from proline requiring ascorbic acid • If there is defective collagen formation, endochondral bone formation stops since oste, intercellular substance is no longer formed • Vitamin C is involved in hydroxylation reactions in the synthesis of steroids and epinephrine • Ascorbic acid also aids iron absorption by reducing it to ferrous state in the stomach, spares vitamin A, vitamin E and some B vitamins by protecting them from oxidation, and enhances the utilization of folic acid by aiding the conversion of folate to tetrahydrofolate Etiology: • More common 6-24 months • May develop in breastfed infant if mother’s diet deficient • Improper cooking practices produce significant nutrient losses & faulty dietary habits

49. Ascorbic Acid Deficiency (Scurvy) Clinical Manifestations: • Early stages are vague symptoms of irritability, digestive disturbances & anorexia • Mild vitamin C deficiency signs include ecchymoses, corkscrew hairs and the formation of petechiae due to increased capillary fragility resulting from weakened collagen fibrils • Severe deficiency results in decreased wound healing, osteoporosis, hemorrhaging, bleeding into the skin and friable bleeding gums with loosened teeth • A presenting feature is an infant w/ painful, immobile legs (pseudoparalysis), edematous in “frog position” & occasionally w/ mass • There is depression of sternum w/ a “rosary of scorbutic beads at the costochondral junction due to subluxation of the sternal plate • Orbital or subdural hemorrhages, melena & hematuria may be found • Low grade fever & anemia usually present • Impairment of growth & development

50. Ascorbic Acid Deficiency (Scurvy) Diagnosis: • History of vitamin C-deficient diet • Clinical picture • Therapeutic test • X-ray findings in the long bones: • Most prominent & early change is simple knee atrophy • Shaft trabeculae cannot be distinguished giving “ground glass appearance” • Cortex reduced to “pencil-point thinness” • Zone of well-calcified cartilage, white line of Fraenkel, seen as irregular & thickened white line w/c • Zone of rarefaction, a linear break in bone proximal & parallel to white line under at metaphysis • Calcifying subperiosteal hemorrhages cause bone to assume a dumb-bell or club shape