Severe malnutrition Nutrition rehabilitation centres Nutrition rehabilitation centres can have a valuable educative effect in teaching mothers appropriate ways to wean and feed young children. The experience with these centres is that they have not been as successful as originally hoped, Patt of this failure is due to unrealistic expectations from the centres and part due to failure to appreciate the nature of the illness itself, with undue emphasis being placed upon the provision of a high protein diet Children are only likely to benefit if all the underlying disease problems are recognized and adequately treated. In particular the anorectic child is unlikely to benefit from simply being offered more food, regardless of how appetizingly it has been made. Health centres Local clinies where minor ailments, infections. cuts, and diarrhoea ccan be seen and treated have an important role to play in the pre- vention of malnutrition, [National food and nutrition policies Many countries, recognizing the important role that adequate nutrition and good health play in national development, have formulated some form of national food and nutrition poliey. By their very nature these policies involve many different sectors of | the society and therefore it is essential that decisions be taken at the highest level of government, and they enjoy the support of the political will and administrative skill, if they are to be suecessul Furthermore, most policies require considerable co-operation at an international level. Conclusion ‘The problems raised by severe undernutrition cover the whole spectrum of human experience. from that of the individual to that of society. Childhood undernutrition is the most common serious illness in the world today. Lessons learnt from the study and man- agement of these children have relevance for malnourished indi- viduals ofall ages and for those in whom malnutrition is secondary to a wide spectrum of disorders, A clear understanding of the aetiology and pathogenesis of this disorder is a prerequisite for designing effective intervention and prevention at an early stage References: Alleyne, G. A. 0., Hay, R. W., Picou, D. Land Whitehead, R. G. (1977), Prowin-energy malnutrition. Arnold. London. Ashworth, A. (19M0). Practical aspects of dietary management during ‘chabilitation [rom severe protein-energy malnutetion. J Human Nur 34. 360-309. Beaton, G. H. and Bengoa. 3. M. (1976). Nutrition in preventive medicine “Monograph Series No 62. World Health Organization, Geneva Biswas, MC and Pinstrup-Andersen, . (1985). Nuiion and development. ‘Oxlord University Press, Oxfor Brozek, J. and Schurch, B. (1984). Malnurition and behaviour: critical ‘assessment of key issues. Nestle Foundation. Switzerland. Golden, M. H. Nand Jackson. A. A. (1986). Generalized malnutition, ‘in basic aed clinical murron (ed. R. K. Chandra). Lange Medical Pub Tications, California, Landman, J.P. and Jackson, A. A. (1981). The role of protein deficiency inthe actiology ofkwashiorkor. W. Ind. Med. J. 20,239, Mata, L.J. (1978). The children of Santa Maria Caugue. Massachusetts Institute of Technology Press. Cambridge. Mas. Cbsen, RE. (1975) Priein-calorie malnuirition. Academic Press, New York Picou, D. Alleyne, G. A, O., Brooke, O.. Kerr, D.S., Miler. C. Jack Son, A.A. Hill, A, Bogues.J-and Patrick, J (1978). Malwaration and [wstroemerits in children: a manual for hospital ereaiment and manage ‘ment, Carbean Food and Nuteition Tastute, Kingston, Jamaica Waterlow. J. C. (1981). Nutrition of man. Be. med. Bull. 37. 1-108. Vitamins The vitamins, essential in the diet. are a group of organic sub- stances that are required in very small amounts for specific met 8.23 bolie reactions within the cell. They are chemically unrelated, but are usually classified according to their solubility in either fat or \water as this in part determines their transport, storage. and excretion in the body. In fact many vitamins are a group of struc turally related compounds (vitaminers) which behave in a similar way physiologically, although in general the main function is limited to one active form to which the related forms are con: verted. ‘Notwithstanding the florid features that characterize the clasi cal presentation of deficiency syndromes, itis far more difficult (in practice) to identify vitamin deficiencies. The main reason for this is that the full blown syndromes represent a late stage in the dis: ease process, a stage that is often dificult to treat as irreparable damage may already have been done. Ideally the deficiency should be identified at an earlier stage, before clinical signs develop, but unfortunately appropriate biochemical tests are cither not readily available, or limited in their usefulness. Part of the reason why clinical signs are a late manifestation is that they only become evident when the metabolic demand for the vitamin exceeds the available supply. However. as a loss of appetite and the development of a catabolic state isa frequent response t0 3 deficiency. demand is unlikely to increase unless there is some ‘ther intervening stress, such as infection. or forced feeding. The patient's appetite represents an “automatic protection’ which can bbe overridden by the use of enteral or parenteral feeding, in a con- trolled environment with a formula diet. Some of the clearest des- criptions of deficiency states, e.g. biotin, have come from this experience. A further concern in patients receiving intravenous nutritional therapy is the specific role that the gastrointestinal flora plays in providing a source of vitamins, ¢.g. vitamin K, As the vitamins represent a varied group of compounds they engage in a wide range of functions, e.g. the B group are co- enzymes, vitamin D acts as a hormone, vitamin E serves to stabi lize membranes, whilst some have a very specific metabolic role e.g. vitamin A/thodopsin. The time taken for clinical signs to develop when the vitamin is absent from the diet will depend upon a number of factors, The most important factor is the extent t0 which the vitamin is stored in the body, but also includes the meta bolic demand. or the rate at which the vitamin is consumed and the other factors that are likely to affect turnover (the presence of activators. competitors. inhibitors). In general there isa sequence of identifiable changes as deficiency develops, with the first (most sensitive) being the demonstration of a metabolic or biochemical lesion, which may or may not have a recognizable clinical corre late. An intermediate stage presents as a covert deficiency. in which the metabolism can handle usual amounts of substrate but the reduced capacity is unable to cope with the stress of an inereased metabolic demand. The final stage of overt clinical deficiency often represents a state of severe illness requiri: ‘urgent intervention. ‘A number of factors determine the mechanism whereby vitamin deficiency might arise (Table 9). Vitamin A Vitamin A deficiency, including xerophthalmia. is one of the most widespread and serious nutritional disorders. First identified is growth factor in 1913, vitamin A is a generic term for about 30 compounds which are f ionine derivatives other than carotenoid, ‘The dietary sources of vitamin A are green leafy vegetables and fruits. The digestion and absorption of vitamin A is closely related to that of fats, requiring pancreatic juice. bile salts. and an intact mucosa, and it is stored as retinol esters in the liver as a complex, with retinol-binding protein (RBP). Vitamin A deficiency blocks the secretion of RBP and protein deficiency impaits its synthesis, Breakdown products of retinol. with no biological activity. are excreted in urine and there is an enterohepatic eycle with biliary excretion and reabsomption. “The vitamin is necessity for normal growth. normal vision, the8.24 Table 9 Major factors affecting the availability of ita 1 Intake 2 Metabolic demand: Absolute requirement Relative to substrate turnover. e.g. thigmine and carbohydrate Availability of precursor. e.g ryptophan:niacin 3 Digestion/absorption/malabsorption Increased gastrointestinal losses: especially fat-soluble vitamins in situations of fat malabsorption 4 Availabilty from food (a) Bound in unavailable form, .g, niacin (b) Losses in preparation: oxidation vitamin © {e) Antimutrients eg. thiamine (a) Stablity with storage 5 Microfloral bacterial interaction: e.g. production, vitamin K ‘consumption. vitamia By 6 Iatrogenic: Medication causing increased requirements Specific vitamin responsive syndromes Therapeutic rather than physiological dosage ‘maintenance of epithelial tissues, and, probably, reproduction, Light sensitive pigments, such as rhodopsin, contain a form of vit amin A. Rhodopsin is bleached by light resulting in liberation of protein and retinol in all trans form. Regeneration of the pigment equites isomerization of retinol back to the cis form, hence the level at which rhodopsin is maintained is dependent on the level of illumination. Because of the large liver stores a deficiency syn drome takes 9 months to develop, and is associated with a loss of appetite and failure to grow. Death is often associated with infec. tion, and the combination of severe undernutrition, measles, and vitamin A deficiency is particularly lethal. The integrity of epithe- lia is impaiced with replacement of normal mucus secreting cells, ‘and Keratinization of epithelia, It has been suggested that vitamin ‘A plays a role in the glycosylation of glycoproteins, specifically ‘mannosyl glycoprotein, thereby affecting the function of cellular ‘The eye signs of vitamin A deficiency, known collectively as xer ophthalmia, cover both the disorder of visual function and the structural changes that affect the conjunctiva and comea. Night blindness, a useful screening tool, correlates closely with other evidence of vitamin A deficiency (Fig. 5). Conjunctival xerosis consists of patches of dry, non-wettable conjunctiva which initially involves the interpalpebral area of the temporal quadrant, but spreads more widely later. Best seen by oblique illumination these lesions are associated with variable degrees of conjunctival thick- ening, wrinkling, and pigmentation. Bitor’s spots. not necessarily specific for vitamin A deficiency, are seen as foamy cheesy ‘material, covering the xerotic surface and consisting of keratinized Fig. 5 The eales sign of vitamin A deficiency is conjunctival xross, dry ‘srinkling ofthe temporal quadtant. (Reproduced courtesy of Dr C.J. K. Henry.) Nutrition conjunctival epithelial cells (Fig. 6). Males are more susceptible than females and responsive lesions disappear within one week of treatment. On careful ophthalmic examination, a majority of chil- dren with either night blindness and/or conjunctival xerosis, will bbe found to have punctate keratopathy. intially inthe inferonasal {quadrant of the cornea. Extension will lead to corneal xerosis, and frank loss of epithelial stroma will lead to ulceration of various sizes and may extend to involve the entire cornea, either partial or full thickness. Even with prompt appropriate therapy. perforation may cause loss of the anterior segment, or even the entire intra- ‘ocular contents. Melting of the full thickness of the comea. keratomalacia, occurs when vitamin A deficieney is found in association with severe undernutrition, and is very unresponsive to treatment (Fig. 7) ‘The clinical features of deficiency are seen when the liver reserves of vitamin A are virtually exhausted, and indicates a ‘medical emergency. The World Health Organization recommends that on diagnosis children above | year of age should receive ret ‘ol palmitate, 110 mg. of retinol acetate, 66 mg orally, or retinol palmitate, 55 mg intramuscularly, The following day. retinol pal ‘mitate, 110 mg, or retinol acetate, 66 mg, orally is repeated. Prior to discharge, or if clinical deterioration ‘occurs, or 2 to 4 weeks later a further dose of retinol palmitate, 110 mg, or retinol acetate 166 mg, should be given, [a an attempt to prevent the disease, pro- phylactic retinol palmitate, 55-110 mg. oF retinol acetate, 33-66 img, has been given on 2 community-wide basis every 4 10 6 months, Care should be exercised with pregnant women as vit. ‘amin A is known to be teratogenic in animals. Fortification of Fig. 7 Severe vitamin A deficiency associated with malnutrition. may result in keratomalacia, and the loss of intraocular contents, (Reproduced courtesy of Dr C.K. Henry.)‘Severe malnutrition foodstuffs, such as sugar in Central America or monosodiumgluta ‘mate in Indonesia, can be effective, provided the population at risk receive the fortified food. Dried skim milk used in food aid programmes should be enriched with vitamin A. Hypervitamino- sis of vitamin A due to excessive intake may present as lethargy. abdominal pain. headaches, and increased intracranial pressure. Vitamin k . Vitamin K, a fat-soluble vitamin, is necessary for the hepatic pro: duction of blood clotting factors, Deficiency is associated with a low plasma prothrombin (factor Il) as well as depressed levels of factors VII. IX, and X. Vitamin K is an essential co-factor for a membrane-bound carboxylase activity. found in liver. kidney. and bone, and modifies the amino acid glutamic acid in the protein chain to carboxyglutamyl residues. The modified protein has par. ticular calcium-binding properties which may be regulated by vit amin D. Vitamin K is widespread in the diet. and also made in an available form by the gastrointestinal microflora. Newborns, especially preterm infants. are at risk of deficiency because of limited placental transfer and a sterile gastrointestinal traet. Clini cal deficiency may occur with antagonists (e. g. warfarin, dicou- marol), gut sterilization with antibiotics, liver or gastrointestinal disease, especially if associated with fat malabsorption. A single parenteral dose of 1-2 mg vitamin K. or its analogue, is recom. mended for newborns immediately after delivery: excessive doses have led to haemolytic anaemia and kernicterus. Vitamin ‘Tocopherol, oF vitamin E. is fat soluble and widely found in food, although the richest source is vegetable oils. number of vita miners, « B. 7. 0, are expressed as tocopherol equivalents, Deficiency can be produced with relative ease in experimental ani- mals leading to a wide range of disorders. In humans. long-term deprivation has produced increased haemolysis which was acceler- ated if the consumption of polyunsaturated fatty acids. was increased. Infants, especially i preterm or malnourished. are sus- ceptible to vitamin E deficiency, and present with a syndrome of anaemia, oedema, and skin changes. Evidence of vitamin E deficiency is seen in fat malabsorption syndromes, particularly ‘those associated with biliary obstruction, Vitamin E functions bo: logically asan integral structural component of membranes, main taining their stability and metabolic integrity. It also acts as an ‘antioxidant, or free radical scavenger. to prevent or minimize lipid peroxidation. acting in concert with a range of other metabolites, ‘especially vitamins A and C, The role of vitamin E in a wide range Of conditions associated with free radical damage oxidant stress is under active investigation. ine (vitamin B, aneurin) There is no effective body store of thiamine, which is widely avail able in fresh foods and cereals, with useful quantities in meat legumes. green vegetables, fruit, and milk. There is little or none in polished rice. sugar. alcohol. fat oF refined foods, and it may be readily lost in cooking. Some foods contain antithiamine factors fish. tannic or caffeic acid. myoglobin, haemoglobin, Thiamine is readily absorbed by passive diffusion with ill-efined active trans- port at low concentrations, Absorption is deereased by alcohol or in the face of folate deficiency. The phosphorylated form. this mine pyrophosphate acts as a co-cnzyme for thiamine pyrophos- phokinase in a range of important metabolic reactions: (@) Oxidative decarboxylation of Keto acids (c.g. pyruvate, ketoglutarate, keto analogues of branched chain amino acids). of mportance in energy metabolism (b) Transketolase (of the pentose phosphate pathway). of importance in the synthesis of fatty acids and ribose for RNA, (6) Condensation reactions involving aldehyde transferases. The most useful biochemical test for deficiency is to assess the effect of added thiamine pyrophosphate on the ia vivo function of 8.25 sed cell transketolase activity. Dietary deficiency of thiamine pro- duces symptoms in one to two months: anorexia. emotional disturbance, paraesthesiae and altered sensation. weakness. dsp ngea, cardiac dysthythmia, and gastrointestinal symptoms. The clinical syndrome beriberi is found in areas where polished rice is the staple diet and in chronic alcoholics, especially ifliver function is impaired. In dry beriberi, a peripheral neuropathy develops with loss oF impairment of sensory. motor. and reflex function with the distal effects being most marked. Wernicke’s encephalo: pathy (Section 21), an acute cerebral disorder found in alcohol abuse and characterized by mental confusion, nystagmus, VIth nd ataxia, represents a medical emergency which is treated early. In wet beriberi, biventricular enlarge- ‘ment of the heart is associated with systemic venous hypertension and bounding arterial pulsation; so-called high output cardiac fail- ure. The onset of heart failure may be sudden in the face of a severe deficiency, and there may be a rapid, dramatic response t0 parenteral thiamine. Infantile beriberi during the first 6 months of| life, presents with aphonia acute cardiac failure. and pseudomen- ingitc signs. Acute deficiency responds well within hours or days to intravenous thiamine, 100 mg followed by 50 mg daily for a week, In the chronic state longer courses may be necessary although there may be irreparable damage. The daily requirement for thiamine is 0.5 mg/1000 kcal Riboflavin (vitamin B,) Riboflavin functions as a co-enzyme in all cells, being the prosthe- tic group for specific favoproteins in the form of flavin mononuc- leotide (FMN) or flavine adenine dinucleotide (FAD). The favoproteins play a central role in oxidation-reduction reactions in which hydrogen atoms are eventually taken up by molecular oxygen. Riboflavin is widely distributed in foods, and is water soluble. [tis absorbed by a specialized transport process, which is influenced by the presence of food or bile, and transported bound to plasma proteins. Flavoproteins are relatively unstable, and readily lost in the urine in conditions of stress, or following the ingestion of oral contraceptives, chlorpromazine/phenothiazine, imipramine/amitryptyline. Riboflavin status is assessed most use fully by measuring the activity of the red cell enzyme glutathione reductase. Aribotlavinosis classically leads to lesions of the lips (Fig. 8). mouth, eyes, skin, and genitalia, but none of these signs is specific. Angular stomatitis and cheilosis develop, with cracking land fissuring of the lips extending to the mucous membranes, Giossitis, papillary atrophy, and magenta tongue may be present Scrotal or vulval dermatitis has been well described in which intense itching leads to desquamation and secondary excoriation, Eye lesions include photophobia, corneal vascularization, and ‘cataract. [n addition dyssebacea of the naso-labial folds, anaemia, hair loss, degeneration of nerve tissue, ataxia, personality changes, retarded intellectual development, and fatty liver have been described. The prevalence of riboflavin deficiency. especialy in pregnant women and newborns, may he much greater than pre viously appreciated. Recent work from the Gambia has suggested that widespread riboflavin deficiency may represent one of the most important nutritional problems of groups with marginal putitional status. Pyridoxine (vitamin Bs) Vitamin B, covers three pyridine derivatives occurring in food. pyridoxal and pyridoxamine in animal products. and pyridoxine in plants, which are converted to the active pyridoxal phosphate in humans. Absorption is non-saturable. and pyridoxal is carried in red cells and plasma, Pyridoxal phosphate is bound to the encyme elycogen phosphorylase in muscle, hence per cent of the pyti- ‘doxal is of limited availability unless muscle is eatabolized. Pyri doxal also has « major role in the intermediary metabolism of amino acids, Assessment of the aminotransferase reaction forms the basis of tests for pyridoxal status. Experimental deficiency leads to loss of appetite and lassitude, There is increased oxaluria,8.26 Nutrition Fig. 8 In riboflavin deficiency angular stomatitis, cheilsis, gloss, and papillary atrophy may be present with a tendeney to urinary stone formation, Infants with low stores fare at Fisk, especially if their mothers have used oral contracep- tives over jong periods. Hyperirritablity, convulsions, and anae- mia may be seen. Increased requirements have been described in inborn errors of metabolism, alcholism or following treatment of tuberculosis with isoniazid (pyridoxine 10-20 mg/day). Toxicity has been deseribed in men on intakes as high as 300 mg/day Niacin (nicotinic acid) Niacin is the generic term for pyridine 2-carboxylic acid and its erivatives which exhibit the biological activity of nicotinamide. Niacin is very stable, required by all living cells, and hence widely distributed in foodstuffs. Niacin (1 mg) can be formed from tryp- tophan (60 mg). In cereals (especially maize, which is also low in tryptophan) niacin may be bound in a form not readily available biologically, unless the cereal is pretreated with either alkali or by roasting. Niacin is readily absorbed by simple diffusion and per- forms its specific biochemical function as a component of nicotin amide adenine dinucleotide (NAD) or nicotine adenine dinucleo- tide phosphate (NADP) which are central to oxidation- reduction reactions within the cell. Assessment of the niacin status of an individual is based upon the measurement of urinary metabolites. ‘The deficiency state is known as pellagra, with the triad of symp: toms, dermatitis, diarrhoea, and dementia, The disease follows relapsing course with non-specific changes, loss of weight, poor appetite, sore mouth, indigestion, insomnia, and confusion. The skin changes are said to be pathognomonic, the distribution relat ing to exposed surfaces (Fig. 9). Erythema and pruritus develop into discoloured flakes or bullous formation. The flakes become progressively darker, or black, with cracks and fissures, which may lead to weeping lesions and secondary infection (Fig. 10). The characteristic distribution of the rash around the neck and upper chest is known as Casal’s necklace. A conditioned niacin, deficiency may be produced following treatment with isoniazid, in ‘malignant carcinoid where the synthesis of hydroxytrypramine consumes a large proportion of the available tryptophan, or in Fig. 9 The dermatosis of pellagra develops on the exposed area of the skin Fig. 10 Extensive pellagroid changes on the arms and hands, showing dark, flaking skin that leveloped fissures. cracks and weeping areas Hartnup disease (page 9.29). Excessive dietary leucine by inhibit- the conversion of tryptophan to niacin, may cause a deficiency that can be reversed with additional isoleucine in the det. In phat: ‘macological doses nicotinic acid exerts effects, There is a stimula: tory activity on the CNS, reduction of circulating levels. of cholesterol and lipids and reduced blood sugar. with possible predisposition to diabetes, hepatic injury, and peptic ulceration, Vitamin Vitamin C, ascorbie acid, is a water-soluble carbohydrate which is essential in humans because of the absence of the microsomal tenzyme t-ulonolactone oxidase. Vitamin C is not widely present in foodstuffs. being found mainly in fruit and vegetables, and is easily lost in cooking or processing. It is readily absorbed by an‘Severe malnutrition active process. Its specific biochemical function is unclear, but relates 0 its ability to engage in hydroxylation reactions, for example. in the hydroxylation of lysine and proline residues in col- lagen biosynthesis, or trimethyl lysine and butyrobetaine in carni- tine biosynthesis. It also plays a role in the metabolism of iron and copper in maintaining the oxidoreductive state and protects, against free radicals in synergy with vitamin E. ‘Suhelinical deficiency has been associated with ulceration or poor wound healing. Onset or signs of deficiency are insidious with non-specific weakness. fatigue. shortness of breath, and ach- ing in the limbs. Keratosis and plugging of hair follicles leads 10 capillary congestion, proliferation. and haemorrhage. Gum changes are associated with gingivitis. and the swollen spongy appearance gives rise to necrosis and bleeding (Fig. 11). Infantile scurvy develops around the first birthday with irritability, weak ‘unproductive cough. bony tenderness. and pseudoparalysis. Sub- periosteal haemorrhages may be palpable on long bones. Costo- chondral beading is difficult to differentiate from rickets, although there may be subluxation. Anaemia may be present, but gum signs are only found in the presence of erupted teeth, Characteristic radiological signs include subperiosteal haemorrhage, atrophy of the cortex and trabecular structure, widening of the provisional zone of calcification (white line of Frankel) with rarefaction immediately below the zone of provisional ealkfication (corner fracture sign), Laboratory confirmation of the diagnosis is best carried out by estimation of white cell ascorbic acid. Oral treatment is with ascor- bic acid, 100-200 mg for 7 to 10 days, Excess intake has been associated with hypoglycaemia, urico- suria, impaired bactericidal activity of leucocytes, and excessive absorption of food iron. Rebound scurvy has been described in individuals who suddenly stop taking large doses of the vitamin. Pantothenic acid is an essential nutrient for most living. forms, and so is widely available. As an essential component of co: ‘enzyme A, pantothenic acid plays a central role in metabolic pro- Fig. 11 Scorbutie gums have a swollen. spongy appearance, and bleed readily 827 cesses, Clinical deficiency in humans is not well described, but symptoms include abdominal pain nausea, paraesthesiae of the extremities, and "burning feet" syndrome. Biotin deficiency is unusual, as there is extensive synthesis by the gastrointestinal micro-organisms. Biotin is required for the normal Function of a range of carboxylase enzymes involved in the fixation and transfer of CO.. Patients on parenteral nutrition have devel- ‘oped erythematous rash, exfoliative alopecia, waxy pallor, irita- bility, lethargy, mild hypotonia, and organic acidosis, all responsive to biotin. Excessive ingestion of raw eggs may lead to biotin deficiency. The vitamin is bound to avidin in ege white and is metabolically unavailable. Genetic deficiencies of carboxylase enzymes are associated with neurological manifestations that may respond to large doses of biotin, Other vitamins Vitamin D. vitamin Bjs, and folie acid are considered in detail elsewhere (see also Sections 17, 10, 12. and 19), Trace elements At present 14 elements (fluorine, silicon, vanadium, chromium. manganese, iron, cobalt, nickel, copper. zinc, selenium, tin, and iodine) are'required by the body in small amounts so that each ‘comprises less than 0.01 per cent of body weight. They are the ‘essential trace elements. Nine of them occur in the transition series of the periodic table. These elements are all highly reactive chemically, readily forming compounds and catalysing reactions: they are used extensively in industry for these purposes. In the body they function in a similar way: one or more of the elements is required at the active site of more than half the enzymes of the body and virtually all enzymes have mineral elements loosely associated with them which function to stimulate or inhibit their activity at physiological concentrations. Although of great bio- chemical interest, the clinical and nutritional importance of many of the clements has not vet been established. They may occur as ubiquitous dietary contaminants, the dietary requirements for which are met under nearly all circumstances. However, evidence is becoming available that for zine. copper, and selenium, as well as iron and iodine, sections of the population and patients with specific diseases are likely to have clinical deficiency Iron, iodine, and cobalt (only needed in the form of vitamin B,:) are considered elsewhere (page 10.36 and Section 19). Zine Specific and unequivocal severe zinc deficiency has been observed under three ciscumstances. (1) When there is a congenital defect in zine absorption; this presents alter weaning as acrodermatiis enteropathica. 2) When there is a maternal defect in the transpor tation of zine into breast milk, so that the zine concentration is exceptionally low; this presents in the breastfed child as the feral ‘milk syndrome. (3) When patients of any age are given very highly refined therapeutic diets, either enterally or intravenously. which are almost devoid of zine. In each case the clinical presentation is similar. Characteristi cally skin lesions appear first, starting around the nostnils and cor- ners of the mouth as erythematous crusted lesions which do not itch. They spread to the perineum, fingers. toes. and any other ‘area which is traumatized. The skin lesions are sometimes associ ated with a discrete papulo-pustular eruption. resembli vulgaris, or with vesico-bullous lesions, The patient's hair becomes thin and sparse and stops growing. chronic diarrhoea supervenes, and mental apathy or depression is prominent. Most ints develop chronic infections, particularly muco-cutaneous, tandidiasis, but any of the other infections associated with defec tive T-cell function may be present. The patients are anorexic and may deteriorate rapidly ifforce ted8.28 There is no funetional body store of zine. The body is dependent upon a continuous supply: this must come either fom the diet or by catabolizing whole tissue to release the zinc that is locked away in bone and protein. Its probably for this reason that anorexia is feature of zine deficiency. for this will lead to tissue catabolism and the endogenous release of zine Less severe forms of chronic zine deficiency do not present with ‘any specific clinical signs, There isa diminution in the rate of lon- gitudinal growth, so that the children become progressively Stunted, In clinical trials a growth response to zinc is only consist- cently reported in male children. There may also be thymic atrophy tand an impairment of the cell-mediated immune system. so that the patients often present with infections and the underlying mild zinc deficiency is not suspected, ‘An inadequate dietary zine supply may also lead to an abnormal body composition. Lean tissue is much richer in zine than adipose tissue. In patients recovering from severe wasting a low dietary zinc leads to limitation of lean tissue. particularly muscle. synthe sis. and the laying down of disproportionately large quantities of adipose tissue. ‘The diagnosis of zine deficiency cannot be made on the basis of zine determinations alone. There is almost no reduetion in tissue zine concentration even with overt severe zine deficieney. There is ‘profound reduction in plasma concentration. However, a reduc~ tion in plasma zinc is also seen with any acute infection or trauma, There is an extremely rapid clinical response to zine adminis tion. The clinical picture of severe zine deficiency changes within a imatier of hours of zinc administration, often associated with an increase in plasma alkaline phosphatase level. Ifzine deficiency is suspected a therapeutic trial of zinc is, at present. the only way of establishing zine deficiency. It will shortly be possible to diffe tiate the low plasma zine of zine deticiency from that of infection ‘on the basis of a concomitant measurement of plasma metallothio- nein, This sulphur rich zine-binding protein is decreased in zine deficiency and increased with the other causes of hypozincaemia, Copper Copper deficiency occurs in premature infants, weighing less than 1500 g at birth, who are reared exclusively on cow's milk-based diets. Normally, the fetus accumulates copper in the liver before birth, so that its copper concentration is ten times the adult value. Milk is very low in copper. cow's milk having lower levels than human milk. The fetal store is meant to carry the infant from birth to weaning. Premature infants bor before the hepatic store accumulates are thus prone to copper deficiency. which may develop on a milk-based diet Children who are rehabilitated from severe malnutrition over months on exclusively milk-based diets also develop copper deficiency. as do patients that are given therapeutic diets very low in copper, Clinically. copper deficiency presents with osteoporosis (with ccostochondral cartilage cupping, flaring of the metaphyses of long. bones, and pathological fractures), general pallor of the skin and hypochromotrichia and with a hypochromic anaemia which is not responsive to iron supplements. There may also be leucopenia, ‘The features of mild copper deficiency in the human have not bbeen adequately elucidated: they may include hypercholesterolae- mia, decreased HDL fraction of lipoprotein, hyperuricaemia, non-specific ECG abnormalities. and hypercoagulable blood. Plasma copper cannot be used to measure copper status, This is because 90 per cent of plasma copper occurs in the protein caeru- Joplasmin. Caeruloplasmin is an acute phase reactant. secreted in large amounts by the liver in response (0 inflammatory stress Even in copper deficiency the liver can secrete sufficient caerulo- plasmin to elevate the circulating copper concentration. On the ‘other hand abnormalities of hepatic export protein synthesis, such Nutrition as liver disease and malnutrition. ean lead to very low levels of plasma caeruloplasmin and hence copper. Copper deficiency may be suspected if there is a reduction of red cell superoxide dismutase, This enzyme which contains both zine and copper is responsive in animals and in children to dietary copper intake (but not to zine status). No other condition is at present known to affect the level of # deficiency Selenium Selenium is at the active site of the enzyme glutathione peroxi dase. which catalyses the removal of hydrogen peroxide and ‘organic peroxides formed from fatty acids during free radical ‘damage. It thus has a broad role in protecting tissues from oxida ‘Severe selenium deficiency occurs in China giving rise to an endemic cardiomyopathy termed Keshan disease. The main path- ological feature of Keshan disease is multiple focal myocardial necrosis. The patients present with either acute heart failure, car= ddiogenic shock. and pulmonary oedema or with chronic congestive hheart failure and cardiomegaly. Since identification of the cause of this illness in China, selenium supplementation has led to its vir- tual elimination, ‘Selenium deficiency also occurs in malnutrition. where there are low levels of both selenium and glutathione peroxidase in plasma and red cells. These are correlated with the degree of hepatic dys- function, the heart failure sometimes seen during refeeding and the prognosis. However. it is uncertain to what extent these features are directly due to selenium deficiency per se and how far they are due 10 associated deficiencies. As glutathione peroxidase is but one of a series of protective mechanisms against free radical damage (vitamins E, A, C, carotene. glutathione, copper superox= ide dismutase. manganese superoxide dismutase, zinc) itis likely that overt selenium deficiency will only become apparent when several of the mechanisms are compromised or the selenium deficiency is profound ‘The diagnosis of selenium deficiency can be made on the basis of tissue or blood selenium concentrations or by the assay of red cell or platelet glutathione peroxidase activity. However, a defi nite diagnosis should be positively made before selenium adminis- tration as excess selenium i itself toxie and the margin between a ficient and a toxic intake seems to be quite narrow. The requirement for selenium is unknown, from the intakes reported from the Keshan disease area it seems that about 30 jgid is sufficient to prevent the disease: many special diets so not sup. ply this amount, Other trace elements None of the other trace elements have given rise to confirmed cli nical observations in humans under well-controlled conditions. References Barker. B. M. and Bender. D. A. (1980182). Vitamins n medicine 4th edn, Vol. (1980). Vol. 2 (1983). William Heineman Medical Books, Lon: don Golden. M. H. N. (1982), Trace elements in human nutrition. Human Nutr Clin, Nur 36C. 1NS-202 Gyorgy. P. and Pearson, W. N. (1967). The vitamins Vols VI-VIL, Acs fmic Press New Vor. Prasad. AS, (1976). Trace elements in human health and disease. Acs ‘demic Press. New York Sebel Je. W. HL and Har ‘demic Press, New York ‘Underwood. E. J. (1977), Trace elements in human and animals. Nuition “ivedn. Academic Press, New York WHOUNICEF'USAID Helen Keller International VACG_ Mec (1982). Control of vitamin A deficiency and verophuhalania. Teshnical Report Series 672, World Health Organization. Geneva R. S. (1967). The vitamins Vols IV. Acs