NUTRITIONAL DISORDERS

NUTRITIONAL DISORDERS FARHANA ZAKARIA

An adequate diet should contain 1- Energy in the form of carbohydrates , fats , proteins 2- Essential aminoacids and fatty acids to be used as building blocks for synthesis of structural and functional proteins and lipids. 3- Vitamins and minerals- as coenzymes or hormones in vital metabolic pathways

Common causes of undernutrition : 1- Ignorance and poverty 2- Chronic alcoholism 3- Acute and chronic illnesses 4- Self- imposed dietary restriction Other less common causes are malabsorption syndromes, genetic diseases, specific drug therapies and total parenteral nutrition .

PEM • Severe PEM is a serious, often lethal disease. • It is common in third world countries, where up to 25% of children may be affected, and where it is a major factor in the high death rates among children younger than 5 years. • PEM refers to a range of clinical syndromes characterized by a dietary intake of protein and calories inadequate to meet the body's needs. • The two ends of the spectrum are known as Marasmus and Kwashiorkor.

PEM inadequate dietary intake of protein and calories . Diagnosis of PEM: • Body weight for a given height • Fat stores • Muscle mass • Thickness of skin folds • Measurement of serum proteins

There are two protein compartments in the body: • the somatic protein compartment, represented by skeletal muscles, if the somatic protein is catabolized,resultant reduction in muscle mass is reflected by reduced circumference of the midarm. • the visceral protein compartment, represented by protein stores in the visceral organs, primarily the liver. Measurement of serum proteins provides a measure of adequacy of visceral proteins compartment .

The diagnosis of PEM is obvious in its most severe form. • In mild to moderate forms, the usual approach is to compare the body weight for a given height with standard tables; other parameters are also helpful, including evaluation of fat stores, muscle mass, and serum proteins. • With a loss of fat, the thickness of skinfolds (which includes skin and subcutaneous tissue) is reduced. • A child whose weight falls to less than 80% of normal is considered malnourished

Marasmus refers to malnutrition caused primarily by severe reduction in calorie intake. • Results in greater than 60% reduction in body weight adjusted for height and sex. • Child with marasmus suffers growth retardation and a loss of muscle • Subcutaneous fat is also mobilized • The extremities appear emaciated , by comparison , the head appears too large for the body .

Anemia and manifestations of multivitamin deficiencies are present, and there is evidence of immune deficiency, particularly T cell- mediated immunity. • Hence, concurrent infections are usually present .

Kwashiorkor • Protein deprivation is relatively greater than the reduction in total calories. • Marked protein deprivation is associated with severe loss of the visceral protein component and the resultant hypoalbuminemia gives rise to generalized or dependent edema. • Weight is typically 60% to 80% of normal.

The true loss of weight is masked by the increased fluid retention (edema) • Relative sparing of subcutaneous fat and muscle mass. • Characteristic skin lesions with alternating zones of hyperpigmentation , areas of desquamation and hypopigmentation , giving a flaky paint appearance. • Hair changes include overall loss of colour or alternating bands of pale and darker hair, straightening, line texture, and loss of firm attachment to the scalp.

Enlarged fatty liver • Apathy , listlessness , loss of appetite. • Other vitamin deficiencies present • Defects in immunity and secondary infections.

Secondary PEM • Common complication in advanced cancer and AIDS Physical signs include: • Depletion of subcutaneous fat in the arms , chest wall , shoulders or metacarpal regions • Wasting of the quadriceps femoris and deltoid muscles • Ankle or sacral edema.

Morphology in PEM Central anatomic changes include: • Growth failure • Peripheral edema in kwashiorkor • Loss of body fat and atrophy of muscle more marked in marasmus

Kwashiorkor • Liver is enlarged and fatty , superimposed cirrhosis is rare. • Small bowel shows a decrease in the mitotic index in the crypts of the glands , associated with mucosal atrophy and loss of villi and microvilli. • Concurrent loss of small intestine enzymes occur most often manifested as disaccharidase deficiency . • Thus infants may initially not respond to a full strength milk based diet. • With treatment mucosal changes are reversible.

Bone marrow in both are hypoplastic mainly because of decreased no. of red cell precursors. • Anaemia is usually present , most often microcytic hypochromic. • But a concurrent deficiency of folates may lead to a mixed microcytic macrocytic anaemia.

Brain: In some infants who suffer PEM during the first 1-2 years show cerebral atrophy, reduced number of neurons, impaired myelination of the white matter. • Other changes: • Thymic and lymphoid atrophy (More marked in kwashiorkor). • Anatomic alterations induced by intercurrent infections, • Deficiencies of other required nutrients such as iodine and vitamins

KWASHIORKOR • The infant shows generalised oedema, seen in the form of puffiness of the face, arms and legs.

Anorexia Nervosa and Bulimia • Anorexia nervosa is self-induced starvation, resulting in marked weight loss. • Bulimia is a condition in which the patient binges on food and then induces vomiting. • These eating disorders occur primarily in previously healthy young women who have developed an obsession with attaining thinness.

Clinical findings: • Amenorrhea, • Other common findings, related to decreased thyroid hormone release, include cold intolerance, bradycardia, constipation, and changes in the skin and hair.

The skin becomes dry' and scaly and may be yellow owing to excess carotene in the blood. • Body hair may be increased but is usually fine and pale (lanugo). • Bone density is decreased • As expected with severe PEM, anemia, lymphopenia, and hypoalbuminemia may be present. • A major complication of anorexia nervosa is an increased susceptibility to cardiac arrhythmia and sudden death, resulting in all likelihood from hypokalemia.

BULIMIA • In bulimia, binge eating is the norm. Huge amounts of food, principally carbohydrates are ingested, only to be followed by induced vomiting. • Although menstrual irregularities are common, amenorrhea occurs in less than 50% of bulimic patients • The major medical complications (1) electrolyte imbalances (hypokalemia),which predispose the patient to cardiac arrhythmias; (2) pulmonary aspiration of gastric contents; and (3) esophageal and stomach cardiac rupture.

Vitamin Deficiencies • Thirteen vitamins are necessary for health; four-A, D, E, and K-are fat-soluble, and the remainder are water soluble. • Certain vitamins can be synthesized endogenously-vitamin D from precursor steroids, vitamin K and biotin by the intestinal microflora, and niacin from tryptophan, an essential amino acid.

VITAMIN A • The fat-soluble vitamin A is actually a group of related natural and synthetic chemicals that exert a hormone-like activity or function. • Retinol is the most important form of vitamin A; it is the transport form and, as the retinol ester, also the storage form. It is oxidized in vivo to the aldehyderetinal (the form used in visual pigment) and retinoic acid. • Important dietary sources of vitamin A are animal-derived (e.g., liver, fish, eggs, milk, butter). Yellow and leafy green vegetables such as carrots, squash, and spinach .

Retinoids, refers to both natural and synthetic chemicals that are structurally related to vitamin A but do not necessarily have vitamin A activity. • As with all fats, the digestion and absorption of carotenes and retinoids require bile, pancreatic enzymes, and some level of antioxidant activity in the food. • Retinol, whether derived from ingested esters or from β-carotene , is transported in chylomicrons to the liver for esterification and storage.

More than 90% of the body's vitamin A reserves are stored in the liver, predominantly in the perisinusoidal stellate (lto) cells. • In healthy persons who consume an adequate diet, these reserves are sufficient for at least 6 months' deprivation. • Retinoic acid, on the other hand, can be absorbed unchanged; it represents a small fraction of vitamin A in the blood and is active in epithelial differentiation and growth but not in the maintenance of vision.

When dietary intake of vitamin A is inadequate, the retinol esters in the liver are mobilized, and released retinol is then bound to a specific retinol-binding protein (RBP), synthesized in the liver. • The uptake of retinol by the various cells of the body is dependent on surface receptors specific for RBP, rather than for the retinol. • Retinol is transported across the cell membrane, where it binds to a cellular retinol-binding protein, and the RBP is released back into the blood.

In humans, the best-defined functions of Vitamin A are: • Maintaining normal vision in reduced light • Potentiating the differentiation of specialized epithelial cells, mainly mucus-secreting cells • Enhancing immunity to infections, particularly in children and particularly measles • The retinoids, β-carotene, and some related carotenoids have shown to function as photoprotective and antioxidant agents.

The visual process involves four forms of vitaminA-containing pigments: rhodopsin in the rods, and three iodopsins in cone cells, • The synthesis of rhodopsin from retinol involves (1) oxidation to all-trans-retinal, (2) isomerizationto 11-cis-retinal, and (3) interaction with the rod protein, opsin, to form rhodopsin. • When a photon of light impinges on the dark-adapted retina, rhodopsinundergoes a sequence of configurationalchanges to ultimately yield all-trans-retinal and opsin.

In the process, a nerve impulse is generated (by changes in membrane potential) that is transmitted via neurons from the retina to the brain. • During dark adaptation, some of the all-trans-retinal is reconverted to 11-cis-retinal. but most is reduced to retinol and lost to the retina,

Vitamin A plays an important role in the orderly differentiation of mucus-secreting epithelium; when a deficiency state exists, the epithelium undergoes squamous metaplasia and differentiation to a keratinizing epithelium. • Host resistance to infections, stimulate the immune system, possibly through the formation of a metabolite called 14-hydroxyretinol.

Vitamin A deficiency • One of the earliest manifestations of vitamin A deficiency is impaired vision, particularly in reduced light (night blindness). • Because vitamin A and retinoids are involved in maintaining the differentiation of epithelial cells, persistent deficiency gives rise to a series of changes,

Collectively, the ocular changes are referred to as xerophthalmia (dry eye). • First, there is dryness of the conjunctiva (xerosis conjunctivae) as the normal lachrymal and mucus-secreting epithelium is replaced by keratinized epithelium. • This is followed by the build-up of keratin debris in small opaque plaques (Bitot spots) and, eventually, erosion of the roughened corneal surface with softening and destruction of the cornea (keratomalacia) and total blindness.

VITAMIN A DEFICIENCY

The epithelium lining the upper respiratory passage and urinary tract is replaced by keratinizing squamous cells (squamous metaplasia). • Loss of the mucociliary epithelium of the airways predisposes to secondary pulmonary infections, and desquamation of keratin debris in the urinary tract predisposes to renal and urinary bladder stones. • Hyperplasia and hyperkeratinization of the epidermis with plugging of the ducts of the adnexal glands may produce follicular or papular dermatosis.

Vitamin A Toxicity • Both short- and long-term excesses of vitamin A may produce toxic manifestations • The clinical consequences of acute hypervitaminosis A include headache, vomiting, stupor, and papilledema, symptoms suggestive of brain tumor. • Chronic toxicity is associated with weight loss, nausea, and vomiting, • Although synthetic retinoids used for the treatment of acne are not associated with the complications listed, their use in pregnancy should be avoided owing to a, well-established increase in the incidence of congenital malformations.

VITAMIN D • The major function of the fat-soluble vitamin D is the maintenance of normal plasma levels of calcium and phosphorus. • With respect to tetany, vitamin D maintains the correct concentration of ionized calcium in the extracellular fluid compartment required for normal neural excitation and relaxation of muscle. • Insufficient ionized calcium in the extracellular fluid results in continuous excitation of muscle, leading to the convulsive state, hypocalcemic tetany.

Metabolism of Vitamin D • The major source of vitamin D for humans is endogenous synthesis in the skin by photochemical conversion of a precursor, 7-dehydrocholesterol, via the energy of solar or artificial ultraviolet (UV) light. • Depending on the skin's level of melanin pigmentation, which absorbs UV light, and the amount of exposure to sunlight, about 90% of the vitamin D needed is endogenously derived. • Only the small remainder must be obtained from dietary sources, such as deep-sea fish, plants, and grains; this requires normal fat absorption. • In plant sources, vitamin D is present in its precursor form (ergosterol), which is converted to vitamin D in the body.

Metabolism of vitamin D as follows • Absorption of vitamin D along with other fats in the gut or synthesis from precursors in the skin. • Binding to plasma α1-globulin (D-binding protein) and transport to liver. • Conversion to 25-hydroxyvitamin D (25-0H-D) by 25-hydroxylase in the liver. • Conversion of 25-0H-D to 1,25-dihydroxyvitamin D [1,25(OH)2-D] by α1-hydroxylase in the kidney; biologically this is the most active form of vitamin D.

The production of 1,25(OH)2-D by the kidney is regulated by three mechanisms: • In a feedback loop, increased levels of 1,25(OH)2-D down-regulate synthesis of this metabolite by inhibiting the action of α1-hydroxylase, and decreased levels have the opposite effect. • Hypocalcemiastimulates secretion of parathyroid hormone (PTH), which in turn augments the conversion of 25-0H-D to 1,25(OH)2-D by activating α1-hydroxylase. • Hypophosphatemia directly activates α1-hydroxylase and thus increases formation of 1,25(OH)2-D.

The active form of vitamin D • Stimulates intestinal absorption of calcium and phosphorus • Collaborates with PTH in the mobilization of calcium from bone • Stimulates the PTH-dependent reabsorption of calcium in the distal renal tubules

The effects of vitamin D on bone depend on the plasma levels of calcium. On the one hand, with hypocalcemia, 1,25(OH)2-D collaborates with PTH in the resorptionof calcium and phosphorus from bone to support blood levels. • On the other hand, vitamin D is required for normal mineralization of epiphyseal cartilage and osteoidmatrix. • Vitamin D favors the formation of osteoclasts from their precursors (monocytes) • The main function of vitamin D may be to maintain calcium and phosphorus at supersaturated levels in the plasma.

Vitamin D clearly activates osteoblasts to synthesize the calcium-binding protein, osteocalcin, involved in the deposition of calcium into osteoid matrix and may thus contribute to bone mineralization.

Vitamin D-deficiency • Rickets in growing children and osteomalacia in adults are worldwide skeletal diseases. • They may result from deficient diets, but probably more important is limited exposure to sunlight (heavily veiled women, children born to vitamin D-deficient mothers, northern climates with scant sunlight).

Rickets : The bowing of legs in a toddler due to the formation of poorly mineralized bone

A deficiency of vitamin D tends to cause hypocalcemia. • When hypocalcemia occurs, PTH production is increased, which • activates renal α1-hydroxylase, thus increasing the amount of active vitamin D and calcium absorption; • mobilizes calcium from bone; • decreases renal calcium excretion; and • increases renal excretion of phosphate. • Thus, the serum level of calcium is restored to near normal, but hypophosphatemia persists, and so mineralization of bone is impaired.

CAUSES OF RICKETS OR OSTEOMALACIA 1. Decreased endogenous synthesis of vitamin D • a. Inadequate exposure to sunlight • b. Heavy melanin pigmentation of skin (blacks) 2. Decreased absorption of fat-soluble vitamin D in the intestine • a. Dietary lack • b. Biliary tract, pancreatic, or intestinal dysfunction 3. Enhanced degradation of vitamin D and 25-0H-D • a. Phenytoin, phenobarbital, rifampin induction of cytochrome P-450 enzymes 4. Impaired synthesis of 25-0H-D • a. Diffuse liver disease

5. Decreased synthesis of 1,25(OH)2-D • a. Advanced renal disease with failure • b. Vitamin D-dependent rickets type I (inherited deficiency of renal α1-hydroxylase) 6. Target organ resistance to 1,25(OH)2-D • a. Vitamin D-dependent rickets type II (congenital lack of or defective receptors for active metabolite) 7. Phosphate depletion • a. Poor absorption-long-term use of antacids, which bind phosphates and render them insoluble • b. Renal tubular disorders, acquired or genetic, causing increased excretion

NUTRITIONAL DISORDERS