Pathology of Nutritional Disorders

Muriel Lambert, Ph.D. December 5, 2003 (Friday)

10:00 am

NUTRITIONAL DISORDERS

There are three broad categories of causes for nutritional imbalances. The first is inadequate or excessive intake. The second is poor digestion and absorption. The third is an increased requirement due to physical activity, rapid growth, infection, acute or chronic illness, pregnancy, drug therapy, or increased loss of nutrients.

In economically under-developed areas calorie and protein deficiencies are presently the most important nutritional problems. Vitamin deficiencies usually coexist with protein-calorie deficiency. In economically developed areas, on the other hand, there is excessive intake of certain types of food, particularly lipids, and inappropriate eating patterns sometimes result invitamin deficiencies.

The major nutritional disturbances result from imbalances in (1) proteins, carbohydrates and fats, (2) vitamins and (3) minerals and water.

I. PROTEIN, CARBOHYDRATE, AND LIPID IMBALANCES

In addition to a minimal overall intake of protein, carbohydrates, and lipids, there are eight essential amino acids that are necessary in the human diet. These are: tryptophan, lysine, phenylalanine, leucine, isoleucine, threonine, methionine and valine. There are also threeessential fatty acids: arachidonic, linoleic and linolenic. Some of the major diseases resulting from imbalance of these essential nutrients are described below.

A. Protein-Energy Malnutrition

Protein-energy malnutrition is currently an important cause of child death in many parts of the world. The two main clinical syndromes are kwashiorkor and nutritional marasmus.

1. KwashiorkorKwashiorkor results from a dietary deficiency of protein, usually in the presence of an adequate caloric intake.

a. Occurrence:1) Mainly in children 1 to 3 years of age2) Common in many underdeveloped countries and in poverty stricken areas of

developed countries3) Most prevalent during the weaning period when the child's diet changes from

maternal milk to primarily carbohydrates

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Dr. M. Lambert - Nutrition

b Clinical Manifestations:1) Growth failure2) Edema3) Hepatomegaly (liver enlargement)4) Anemia5) Hair changes - changes in texture, color, strength6) Dermatoses - wax paper-type desquamation, depigmentation and

hyperpigmentation7) Apathy, anorexia (loss of appetite), listlessness8) Impaired intelligence

c. Histopathology1) Atrophy of the mucosa of the small bowel2) Erythroid hypoplasia in the bone marrow3) Decrease in number of lymphocytes4) Fatty change of the liver

2. Nutritional marasmusMarasmus is a state of malnutrition resulting from a deficiency of total calories.

a. Occurrence1) Common in nearly all underdeveloped countries2) Common in children under 1 year of age3) May occur secondary to such diseases as hepatic fibrosis, celiac disease or

overwhelming infection

b. Clinical Manifestations1) Growth failure2) Wasting - little or no subcutaneous fat, loss of muscle3) Growth retardation4) Ravenous appetite5) Alert mental state6) Many of the manifestations of kwashiorkor except edema

c. Histopathology1) Erythroid hypoplasia of the bone marrow

3. Marasmus-KwashiorkorKwashiorkor and marasmus can be regarded as two extremes of protein-calorie malnutrition; most cases of protein-calorie malnutrition, however, are intermediate between the two. These patients usually manifest other deficiencies as well, particularly of dietary vitamins and manganese.



4. Marasmus-like and kwashiorkor-like syndromesa) Secondary forms of these two syndromes may develop in chronically or acutely ill

hospitalized patientsb) Takes weeks or months to develop

B. Obesity

This type of malnutrition is prevalent in the U.S. and other developed countries. It is characterized by:

1. Abnormally increased adipose tissue which is the result of caloric intake greater than energy expenditure.

2. High mortality rate associated with an increased risk for development of many diseases (cardiovascular and pulmonary diseases, hypertension, cholelithiasis (gallstones) and diabetes mellitus.

3. Genetic influences and environmental factors play an important role in human obesity

4. Obese children and adolescents are a major source for the relatively intractable adult obesity.

C. Lipid Disorders

1. Marked increases in incidence of arteriosclerosis and its complications, particularly coronary heart disease, are associated with metabolic disorders in which blood lipidsare elevated.

2. Levels of triglycerides and cholesterol are the factors most closely associated with development of these diseases.

3. Dietary factors are important in determining lipid and cholesterol levels. Serum cholesterol can be reduced by lowering dietary intake of saturated fats and cholesterol

and increasing the intake of polyunsaturated fats.

4. Inherent metabolic traits are also important factors in determining serum cholesterollevels.



II. VITAMIN IMBALANCES

Vitamins are chemically unrelated organic substances that are required for specific metabolic reactions; they are not adequately synthesized by the individual and are therefore essential in the diet in minute amounts.

Traditionally vitamins are classified according to their solubility in water or fat and physiologically this property determines their patterns of transport, excretion and storage. A large number of the vitamins form specific coenzymes.

At the present time it is difficult to precisely correlate the biochemical and physiological functions of individual vitamins with the clinical manifestations of their deficiencies.

A. Water Soluble Vitamins

This group of vitamins is rapidly and readily absorbed from the alimentary canal. Figure1 shows some of the key roles vitamins play as catalysts in the metabolism of carbohydrates, fats and proteins. The more important ones, described below, are markedwith an asterisk(*).*1. Vitamin B1 (Thiamine)

a. Chemistry and Biochemical Function. Thiamine is part of the coenzyme, thiamine pyrophosphate (TPP), which is an important factor in carbohydrate metabolism.

1) TTP has three important functions: (a) regulates oxidative decarboyxlation of pyruvate and a-ketoglutrate leading to synthesis of ATP (Fig. 1); (b) involved in glucose oxidation (pentose phosphate pathway); (c) maintains neural membranes and normal nerve conduction (chiefly of peripheral nerves).

2) Thus, the organ systems most severely affected by thiamine deficiency are those most dependent upon carbohydrate metabolism (i.e. the heart andnervous system).

b. Pathology of Thiamine Deficiency. Thiamine deficiency is widespread in the orient where the diet of the population consists largely of polished or refined rice.

It is also associated with chronic alcoholism. The best documented thiamine deficiency state is beriberi. Beriberi in Singhalese means "weakness". The changesoccurring in beriberi are, for the most part, confined to the heart and nervous system. Beriberi can be divided into several syndromes:

1) Wet Beriberi (Acute)a) Principally characterized by chronic heart failure; the heart is flabby and

dilated



1) Wet Beriberi (Acute) - continued b) Peripheral vasodilatationc) Extensive edema secondary to cardiac failure

2) Dry Beriberi (Chronic)a) Peripheral neuropathy, with degenerative changes also ccurring in the

central nervous systemb) Myelin egeneration and disruption of axonsc) Wrist-drop, foot-drop, marked wasting of lower extremities

3) Wernicke's disease - This disease is considered a subtype of dry beriberi and is mainly associated with chronic alcoholism. It is principally characterized by degenerative changes in the brain and central nervous systems, oculomotor disturbances and ataxia.

4) Korsakoff's pyschosis - This is usually associated with Wernicke's disease (Wernicke-Korsakoff syndrome) and is characterized by loss of memory ofthe immediate past and often elaborate confabulation which attempts to conceal this amnesia, generally without success.

c. Antagonists of thiamine - In certain fish (e.g. carp) a heat-labile enzyme (thiaminase) has been found which destroys thiamine. In those countries where large amounts of raw fish are eaten, thiamine deficiency sometimes occurs. Up to 3% of Japanese are thiamine deficient for this reason.

*2. Vitamin B2 (Riboflavin)

a. Chemistry and Biochemical Function - Riboflavin forms part of the structure of two coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which play an important role in both protein and energy metabolism. They serve as carriers in the electron transport system and participate in the oxidation of amino acids and purines (Fig. 1).

b. Riboflavin Deficiency - Symptoms first appear in the skin and mucous membranes. Other clinical signs are also seen.

1) Cheilosis: This is usually the first and most characteristic sign of the deficiency. It is characterized by cracks or fissures and crusts at the angles of the mouths which may extend into the mucous membrane inside the mouth.

2) Glossitis: This lesion of the tongue results from atrophy of the mucosa. This may be accompanied by superficial submucosal inflammation, producing a bright red or magenta hue.


Dr. M. Lambert - Nutritionb. Riboflavin Deficiency - continued

3) Eye Change: In avascular tissues, such as the cornea oxidation takes place by

means of a riboflavin-containing enzyme. In riboflavin deficiency attempts at oxygenation occur through neovascularization of these tissues.

4) Dermatitis: A scaling, greasy dermatitis occurs especially over the nasolabial folds with scrotal and vulvar lesions also common.

5) Retarded intellectual development has been noted in riboflavin-deficient children.

*3. Niacin (Nicotinic Acid)

a. Chemistry and Biochemical Function - Niacin is metabolically converted to nicotinamide, a component of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) which functionin electron transfer. These coenzymes are of major importance in glycolysis andcellular respiration where in the reduced state they donate hydrogens to the cell respiratory chain (Fig. 1).

b. Niacin deficiency 1) Pellagra. This disease is associated with corn (maize) eating peoples. Maize

is poor in usable niacin and very low in tryptophan content (niacin is synthesized from dietary tryptophan). Pellagra may not be a simple niacindeficiency; deficiency of several of the other B vitamins may also be involved.

a) Clinical Manifestations - Clinically the disease is characterized by the four D's - dermatitis, diarrhea, dementia, and death.

i. Dermatitis - Skin lesions tend to occur in regions of the body exposed to sunlight or chronic irritation such as the face, neck, hands, wrists, elbows, and knees. The lesions on the upper chest and lower neck are known as Casal's necklace.

ii. Diarrhea - This is presumed to be due to mucous membrane lesions, most prominent in the esophagus, stomach, and colon.

iii. Dementia - Degeneration of the ganglion cells of the brain and thetracts of the spinal cord occurs.

iv. Death - Pellagra may be quite rapidly fatal.



4. Pyridoxine (B6)

a. Chemistry and Biochemical functions. Pyridoxine is the accepted name of a group of three closely related compounds which are converted in the body to the coenzyme pyridoxal phosphate, whose major function is amino acid or protein metabolism (Fig. 1), and which is also a cofactor in the production of the inhibitory amine, a-amino butyric acid.

b. Pyridoxine deficiency. 1) Biochemical evidence of pyridoxine deficiency occurs in uremia and cirrhosis.

It can also occur with pharmacologic agents such as penicillamine. A significant percentage of women using oral contraceptives have altered pyridoxine metabolism.

2) The most common cutaneous sign of pyridoxine deficiency is a dermatitis of the face, scalp, neck and shoulders. Central nervous system alterations suchas somnolence and confusion occur commonly. Pyridoxine deficiency is also common in chronic alcoholics.

5. Pantothenic acid (B5)

a. Chemistry and Biochemical functions. Pantothenic acid is a component of coenzyme A (CoA). Pantetheine, a derivative of pantothenic acid, is the functional unit of coenzyme A and plays a vital role in numerous metabolicprocesses.

b. Deficiency of Pantothenic Acid. Though pantothenic acid is of physiological importance, evidence for lesions in man from deficiency of this vitamin are inconclusive. The "Burning Feet" syndrome, consisting of severe paresthesias and tenderness of the feet, observed among prisoners of war (in World War II) and in malnourished subjects in the Far East, responded to preparations containing pantothenic acid and probably represents a specific manifestation of deficiency of this vitamin.

*6. Vitamin B12 (Cyanocobalamin)

a. Chemistry and Biochemical functions. Vitamin B12 is the largest of all the vitamins and has been isolated in several different forms, of which cyanocobalaminis the principal one.

1) The absorption of vitamin B12 from the gastrointestinal tract is dependent on a constituent of the gastric juice designated "intrinsic factor," which is believed to interact with the vitamin and protect it during its transit to the ileum where it is absorbed.



*6. Vitamin B12 (Cyanocobalamin)

2) At least 5 different vitamin B12 coenzymes have been identified. The mechanism by which the B12 coenzymes function is not clear. Many of their

functions appear to be closely linked with tetrahydrofolic acid (FH4) in the metabolism of one-carbon groups. Present evidence suggests that theyparticipate in nucleic acid synthesis, protein synthesis, particularly biosynthesis of amino acids, and in lipid metabolism.

b. Vitamin B12 Deficiency. Primary dietary deficiency of vitamin B12 is rare. Deficiency is usually induced by mechanisms which include; (1) inadequate production of intrinsic factor; (2) interference with B12 or intrinsic factor function;(3) impaired absorption; or (4) loss in the body.

Deficiency produces cellular changes throughout the body, the most seriousconsequences of which is Pernicious Anemia which consists of:

1) Megaloblastic Anemia - characterized by erythroblasts that are larger than normal and which have an altered nuclear- cytoplasmic ratio. This is related todefective DNA synthesis.

2) Neurological disorders - Degeneration of the spinal cord (subacute combined system degeneration) occurs. This will be discussed in more detail in later lectures.

*7. Folic Acid (Pteroylmonoglutamic acid) (Vitamin M)

a. Biochemistry and Biochemical function. The active form of folic acid is tetrahydrofolic acid (FH4). This coenzyme is a carrier for and donates one carbongroups and is mainly involved in the biosynthesis of the nucleic acids necessaryfor DNA synthesis. It is necessary for mitosis in actively dividing cells such asthose of the alimentary tract and bone marrow.

b. Folic Acid Deficiency. The typical reaction to folic acid deficiency is a megaloblastic red cell maturation in the bone marrow with a resulting megaloblastic anemia which may be accompanied by intestinal malabsorption and glossitis.Certain vitamin B12 deficiency findings may be attributed to a defect in folate utilization.



*8. Vitamin C (Ascorbic Acid)

a. Biochemistry and Biochemical function. Ascorbic acid is a hexose derivative. 1) It functions as a reducing agent required as a coenzyme for the enzymes

proline hydroxylase and lysine hydroxylase, which are important in synthesisof collagen and intercellular cement substance. Hence, Vitamin C is critical forgrowth and tissue repair.

2) Vitamin C has antioxidant properties. It can directly scavenage free radicals in

cells and indirectly regenerate the antioxidant form of vitamin E. Thus vitamins C and E can act in concert.

b. Vitamin C Deficiency. Gross vitamin C deficiency results in the disease scurvy.

Metabolic stress, such as acute illness or surgery, markedly increases requirements for vitamin C. Scurvy sometimes occurs in intensive care units. A lack of vitaminC affects:

1) Capillary Walls. Deficiency of intercellular cement substance and connective

tissue support weakens capillary walls and leads to their rupture and extensive hemorrhage. Hemorrhages are one of the most striking manifestations of scurvy. These occur most often in the subcutaneous tissues (producing petechiae and ecchymoses), joints, nose (epistaxis-nosebleed), and mucousmembranes of the mouth.

2) Bone formation. In scurvy, the principal deficiency is in formation of osteoid matrix, not, as rickets, in mineralization or calcification. As a consequence,

bone growth, formation and strength are severely disrupted. Deficiencies in collagen and cement substance also occur and as a result the periosteum becomes detached and extensive subperiosteal hematomas occur.

3) Wound healing. Ascorbic acid deficiency leads to failure of collagen formation and as a result impaired wound healing. Also there is a constant turnover of collagen in old wounds, so that reopening of old wounds may occur in scurvy.

4) Teeth - Resorption of the alveolar bone may cause the teeth to soften, loosen or fall out.

5) Gingiva - Swelling, hemorrhages and secondary marginal infections of the gingiva may occur.

A patient with scurvy may have some of the above symptoms and not appear seriously ill, however, he or she may suddenly collapse and die.


Dr. M. Lambert - Nutrition 9. Biotin (Vitamin H)

a. Chemistry and Biochemical function. Biotin is a relatively simple monocarboxylic acid. Its primary function is as the coenzyme for enzymatic reactions involving the addition of carbon dioxide to other units (carboxylation reactions). It has also been attributed an important role in the intermediary metabolism of carbohydrates, proteins and fats (Fig. 1).

Raw egg white contains avidin, a protein which combines with biotin and acts as an antagonist. Paradoxically, egg yolk is a very rich source of biotin.

b. Biotin deficiency. Deficiency of biotin can be acquired or genetic. Acquired biotin

deficiency is extremely rare due to its ubiquity among foods and because it is produced by intestinal bacteria. Occasionally biotin deficiency occurs in an individual who has for some reason consumed a diet consisting mainly of raw egg whites. Two forms of genetic biotin deficiency occur, neonatal and infantile. Exfoliative dermatitis has been observed in these infants. Neuropsychiatric changes are noted in all forms of biotin deficiency.

B. Fat Soluble Vitamins

This group of vitamins is absorbed in association with dietary fats and requires the presence of bile salts for adequate uptake from the alimentary canal.

*1. Vitamin A (Retinol)

a. Chemistry and Biochemical function. Vitamin A is a long chain alcohol (retinol) which exists in a number of isometric forms. Vitamin A can be obtained directlyin the diet or more commonly as the proto-vitamin precursors, the carotenes. Themost important of these carotenoids is B-carotene (which consists of twocovalently linked molecules of retinol). The carotenoids present in the diet arecleaved within the intestinal wall to form Vitamin A. Vitamin A has a number of roles, the best understood of which is in vision. The aldehyde of retinol, retinal, isa constituent of the visual pigments rhodopsin and iodopsin, in the rod and conecells, respectively, of the retina.

Vitamin A is necessary for growth and development, and is involved in the normal functioning of the eyes, skin and gonads.



b. Vitamin A Imbalance

1) Hypovitaminosis A a) Night blindness. Visual acuity in subdued light depends on excitation of

rhodopsin in the retina. During the visual process some retinal is degraded, thus a constantly available source of Vitamin A is necessary in order to maintain adequate levels of rhodopsin due to retinal loss. Inadequate levels of Vitamin A result in a loss of vision in low intensity light (night blindness).

b) Epithelial Metaplasia. By an as yet unknown mechanism vitamin A is necessary for the maintenance of mucous membranes and epithelial of the eyes, respiratory, gastrointestinal, and genitourinary tracts, and the lining of numerous gland ducts. Deficiency leads to atrophy and replacement by stratified squamous epithelium which keratinizes.

i. Xerophthalmia - The conjunctional and corneal mucosal surfaces of the eye become dry and rough, and keratin debris accumulates in whitish plaques (Bitot's spots). Visual acuity is impaired.

ii. Keratomalacia. This disease may develop, particularly in children, if Xeropthalmia is left untreated. The corneal surface ulcerates,becomes opaque, and softens. Secondary infection may occur leading to perforation of the cornea and blindness.

iii.

Skin lesions. Even though the skin is normally keratinized, Vitamin A deficiency may lead to hyperplasia and hyperkeratinization of the epidermis.

iv. Squamous metaplasia of epithelium lining the upper respiratory passages and urinary tract. The epithelium lining is replaced by keratinizing squamous cells. This predisposes to secondary pulmonary infections and renal and kidney stones.

c) Immune deficiency. Vitamin A plays some role in host resistance to

infections. It stimulates the immune system. This impairment of immunity, during vitamin A deficiency, leads to high mortality rates from common infections such as measles, pneumonia and infectious diarrhea.

2) Hypervitaminosis A Excess vitamin A can lead to irritability, anorexia, nausea, hepatomegaly,

headaches with increased cerebrospinal fluid pressure leading to hydrocephalus, and hyperkeratosis and desquamation of the skin.



*2. Vitamin D (Ergocalciferol, cholecalciferol)

a. Chemistry and Biochemical function. Several forms of Vitamin D exist, all arise from the irradiation of sterols.

1) In plants, ergosterol is activated by sunlight to form ergocalciferol (D2), and in animals 7-dehydrocholesterol is activated to form cholecalciferol (D3). Both forms of vitamin D undergo metabolic transformation in the liver and kidneys to an active form.

2) Vitamin D deficiency results from three major causes: (1) inadequate intake , (2) chronic liver or kidney disease, or (3) inadequate sun exposure.

3) The major function of vitamin D is the maintenance of normal plasma levels of calcium and phosphorus. Vitamin D facilitates the transport of calcium across intestinal epithelium and its antirachitic activity appears to be due primarily to this function.

b. Vitamin D deficiency. The two main vitamin D deficiency disease states are rickets, which occurs in children, and osteomalacia, occurring in adults, These are characterized by:

1) Failure of mineralization of osteoid matrix leading to marked skeletal deformities in children.

2) Progressive loss of calcium from the matrix of long bones. This is usually evident on X-ray as increased radiolucency of bone. This may lead to: compression fractures of vertebrae and spontaneous fractures.

c. Hypervitaminosis D. Huge overdoses of Vitamin D lead to hypercalcemia, metastatic calcification and hypercalciuria. This last abnormality predisposes toward formation of renal stones. Calcium is also mobilized from the bones with resulting osteoporosis.

3. Vitamin E (tocopherol)

Vitamin E was first described as an antisterility vitamin in 1922 when it was found to prevent resorption of fetuses in pregnant female rats and testicular degeneration in males. The name tocopherol is derived from the Greek tokos (childbirth) and phero

(to bear).

a. Biochemistry and Biochemical function. Several substances, designated collectively as tocopherols, comprise the vitamin E group.



a. Biochemistry and Biochemical function - continued

1) Vitamin E serves as an antioxidant that scavenges free radicals throughout the body.

2) The tocopherols in part protect vitamin A and polyunsaturatedlipids, particularly those in cellular membranes, from destructive oxidation

b. Vitamin E deficiency. The nervous system is a particular target of vitamin E deficiency, for reasons that are not clear, possibly through effects on cell membranes. There is degeneration of axons in the posterior columns of the spinal cord, and loss of nerve cells in the dorsal root ganglia. This leads to depressed or absent tendon reflexes; ataxia, dysarthria, loss of position and vibration sense, loss of pain sensation, muscle weakness and disorders of eye movement.

*4. Vitamin K (Naphtoquinones)

a. Biochemistry and Biochemical function. Vitamin K was named from the Danish word Koagulation. It occurs in several closely related forms, and structurally is similar to vitamin E.

1) Vitamin K is a required cofactor for a liver microsoma carboxylase which

carboxylates glutamate residues.

2) Vitamin K is essential for the synthesis of prothrombin as well as factors VII, IX, and X, which all require carboxylation of glutamate residues for functional activity and in its absence the mechanism for blood coagulation is inadequate.

3) Vitamin K also appears to favor calcification of bone proteins through its ability to facilitate carboxylation of these proteins.

b. Vitamin K deficiency . Avitaminosis K leads to the production of hemorrhagic disease. In adults simple deficiency is rare because of the abundance of this vitamin in common foods and because of its formation by intestinal bacteria. Usually, deficiency is due to chronic liver disease or biliary obstruction. In neonates, its most serious manifestation is intracranial hemorrhage.

c. Hypervitaminosis K. Excessive doses of synthetic vitamin K have lead to hemolytic anemia in infants.



*4. Vitamin K (Naphtoquinones) Posterior columns of three - continued

d. Antagonists - Dicomarol is a naturally occurring antagonist blocking the action of vitamin K. It was originally isolated from spoiled sweet clover and shown to be responsible for hemorrhagic disease observed in cattle and sheep. Commercially it is used in rat poison and medically in the treatment of atherosclerotic heart disease, to reduce the risk of thrombosis in the coronary arteries, and of phlebothrombosis, to reduce new clot formation and subsequent embolization.

III. MINERAL AND WATER IMBALANCE

A. A number of minerals are essential for maintenance of various biological processes. Some of these function entirely as components of enzymes or compounds while others act as structural components and are important in maintaining electrolyte balance. Those minerals known to be essential and which are present in fairly large quantities are: calcium, phosphorous, potassium, sodium, chlorine, magnesium and sulfur.

The principal trace elements include; iron, zinc, copper, selenium, iodine, cobalt, manganese, and molybdenum. The nutritional importance of a few of these are briefly indicated below:

1. Iron. It is an essential component of hemoglobin. A deficiency in iron can lead to iron deficiency anemia in which there is inadequate synthesis of hemoglobin.

2. Iodine. This element is absorbed as iodide and quickly oxidized to iodine in the thyroid, where it becomes a constituent of thyroxine and related compounds. Low dietary intak may lead to simple goiter and hypothyroidism which is endemic in many areas of the world.

3. Zinc. A number of metalloenzymes in the body that regulate lipid, protein and nucleic acid synthesis and degradation require zinc. Premature infants are especially susceptible to zinc deficiency since they are born with inadequate zinc stores and decreased absorptive ability. Disorders of zinc metabolism can occur in alcoholics. Zinc deficiency can also be genetic.

Clinical manifestations of zinc deficiency involve multiple organ systems. Growth retardation and anorexia can occur. There is a lack of genital and secondary sexual development. There are also central nervous system changes, gastrointestinal effects, eye changes, immune abnormalities and severe dermatoses.



4. Copper. It is a component of a number of enzymes such as cytochrome C oxidase. Acquired copper deficiency is rare. Deficiency leads to an impairment of copper-dependent enzymes. Infants with marked protein-energy malnutrition or those on strict cow's milk diets constitute the majority of cases. The kinky hair syndrome is an X-linked recessive disorder of copper metabolism in which hairs have repetitive twisting. Muscular weakness, severe mental retardation abnormal colagen cross-linking can ocur.

B. Water is the most critical of all nutrients. The human body contains more water than any other compound. Approximately 70% of the fat-free body is water. Regulation of body temperature is dependent upon water. Excessive water loss from the body results in dehydration and loss of electrolytes, and replenishing the body water without concurrent repletion of electrolytes leads to water intoxication.


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Pathology of Nutritional Disorders