Basic Pathology: Nutritional diseases

Nutritional diseases
An appropriate diet should provide(1) Sufficient energy, in the form of carbohydrates, fats, and proteins (2) Amino acids and fatty acids to be used as building blocks and (3) Vitamins and minerals, which function as coenzymes or hormones or as in the case of calcium and phosphate, as important structural components. In primary malnutrition, one or all of these components are missing from the diet. In secondary malnutrition, the supply of nutrients is adequate, but malnutrition results from insufficient intake, malabsorption, impaired utilization or storage, excess loss, or increased need for nutrients. There are several conditions that may lead to malnutrition Poverty Infections Acute and chronic illnesses Chronic alcoholism Ignorance and failure of diet supplementation Self-imposed dietary restriction

Protein energy malnutrition (PEM)

Severe PEM is a serious, often lethal disease affecting children. It is common in low-income 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. Malnutrition is determined according to the body mass index ( BMI, weight in kilograms divided by height in meters squared). A BMI less than 16 kg/m 2 is considered malnutrition (normal range 18.5 to 25 kg/m2). In malnourished children, PEM presents as a range of clinical syndromes, all characterized by
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Basic Pathology: Nutritional diseases

a dietary intake of protein and calories inadequate to meet the body's needs. The two ends of the spectrum of PEM syndromes are known as marasmus and kwashiorkor. From a functional standpoint, there are two differentially regulated protein compartments in the body: the somatic compartment, represented by proteins in skeletal muscles, and the visceral compartment, represented by protein stores in the visceral organs, primarily the liver. As we shall see, the somatic compartment is affected more severely in marasmus, and the visceral compartment is depleted more severely in kwashiorkor.

1. Marasmus
A child is considered to have marasmus when weight falls to 60% of normal for sex, height, and age. A marasmic child suffers growth retardation and loss of muscle, the latter resulting from catabolism and depletion of the somatic protein compartment. This seems to be an adaptive response that provides the body with amino acids as a source of energy. The visceral protein compartment, which is presumably more precious and critical for survival, is only marginally depleted, and hence serum albumin levels are either normal or only slightly reduced. In addition to muscle proteins, subcutaneous fat is also mobilized and used as fuel. With such losses of muscle and subcutaneous fat, the extremities are emaciated; by comparison, the head appears too large for the body. Anemia and manifestations of multiple vitamin deficiencies are present, and there is evidence of immune deficiency, particularly T cellmediated immunity. Hence, concurrent infections are usually present, which impose additional nutritional demands.

2. Kwashiorkor
Kwashiorkor occurs when protein deprivation is relatively greater than the reduction in total calories. Less severe forms may occur worldwide in persons with chronic diarrheal states in which protein is not absorbed or in those with chronic protein loss (the nephrotic syndrome), or after extensive burns. In kwashiorkor, marked protein deprivation is associated with severe loss of the visceral protein compartment, and the resultant hypoalbuminemia gives rise to generalized or dependent edema. The loss of weight in these patients
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Basic Pathology: Nutritional diseases

is masked by the increased fluid retention. In further contrast to marasmus, there is relative sparing of subcutaneous fat and muscle mass. Children with kwashiorkor have characteristic skin lesions, with alternating zones of hyperpigmentation, areas of desquamation, and hypopigmentation, giving a flaky paint appearance. Hair changes include overall loss of color or alternating bands of pale and darker hair. Other features that differentiate kwashiorkor from marasmus include an enlarged, fatty liver and the development of apathy, listlessness, and loss of appetite. Vitamin deficiencies are likely to be present, as are defects in immunity and secondary infections.

3. Cachexia
PEM is a common complication in patients with AIDS or advanced cancers, and in these settings it is known as cachexia. Cachexia occurs in about 50% of cancer patients, most commonly in individuals with gastrointestinal, pancreatic, and lung cancers, and is responsible for about 30% of cancer deaths. It is characterized by extreme weight loss, fatigue, muscle atrophy, anemia, anorexia, and edema. Mortality is generally the consequence of atrophy of the diaphragm and other respiratory muscles.

Vitamin deficiencies
Thirteen vitamins are necessary for health; vitamins A, D, E, and K are fatsoluble, and all others are water-soluble.

1. Vitamin A
The important dietary sources of vitamin A are liver, fish, eggs, milk and butter. Yellow and leafy green vegetables such as carrots, squash, and spinach supply large amounts of carotenoids.

Function
Maintenance of normal vision Cell growth and differentiation Metabolic effects of retinoids Host resistance to infections
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Basic Pathology: Nutritional diseases

Deficiency states
1. One of the earliest manifestations of vitamin A deficiency is impaired vision, particularly in reduced light (night blindness). First, there is dryness of the conjunctiva (xerosis conjunctivae) as the normal lacrimal and mucus-secreting epithelium is replaced by keratinized epithelium. This is followed by softening and destruction of the cornea (keratomalacia) and total blindness. 2. 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.
3. Hyperplasia and hyperkeratinization of the epidermis with plugging of the ducts of the adnexal glands may produce follicular or papular dermatitis.

4. Immune deficiency, which is responsible for higher mortality rates from common infections such as measles, pneumonia, and infectious diarrhea.

2. Vitamin D
The major function of vitamin D is the maintenance of adequate plasma levels of calcium and phosphorus to support metabolic functions, bone mineralization, and neuromuscular transmission. Vitamin D is required for the prevention of bone diseases.

Functions
Stimulation of intestinal calcium absorption Stimulation of calcium reabsorption in the kidney Interaction with parathyroid hormone (PTH) in the regulation of blood calcium Mineralization of bone

Deficiency States

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Basic Pathology: Nutritional diseases

Rickets in growing children and osteomalacia in adults are skeletal diseases with worldwide distribution. They may result from diets deficient in calcium and vitamin D, but an equally important cause of vitamin D deficiency is limited exposure to sunlight. Other, less common causes of rickets and osteomalacia include renal disorders causing decreased synthesis of 1, 25dihydroxyvitamin D, phosphate depletion, malabsorption disorders, and some rare inherited disorders.

3. Thiamine (vitamin B1)

The major targets of the thiamine deficiency are the peripheral nerves, the heart and the brain. So persistent thiamine deficiency give rise to three distinctive syndromes: A polyneuropathy (dry beriberi) A cardiovascular syndrome (wet beriberi) Wernicke-Korsakoffs syndrome

Dry beriberi: Dry beriberi is usually a peripheral neuropathy with myelin degeneration and disruption of axons involving motor, sensory and reflex arcs. So these patients present with toe drop, foot drop and wrist drop. The progressive sensory loss is accompanied by muscle weakness and hyporeflexia. Wet beriberi: Wet beriberi is associated with peripheral vasodilatation, leading to more rapid arteriovenous shunting of blood, cardiac failure and eventually peripheral edema. The heart may be markedly enlarge and globular with pale, flabby myocardium. The dilation thins the ventricular walls.

Abdullah-Al-Faysal, Lecturer, SUB.

Basic Pathology: Nutritional diseases

Wernicke-Korsakoff syndrome: In severe deficiency state, in chronic alcoholism, Korsakoff syndrome may appear. Wernicke encephalopathy is marked by ophthalmoplegia, nystagmus, ataxia of gait and derangement of mental function characterized by global confusion, apathy, listlessness and disorientation. Korsakoff psychosis takes the form of serious retrograde amnesia, inability to acquire new information and confabulation.

4. Niacin (vitamin B3)

Niacin can be derived from the diet or may be synthesized endogenously from tryptophan. It is widely available in grains, legumes and seed oils. In maize (corn), it is present in bound form and therefore not absorbable. So the niacin deficiency syndrome, pellagra has appeared among native populations that subsist largely on maize.

Deficiency States
The term pellagra means rough skin. The clinical syndromes identified by the three Ds: dermatitis, diarrhea and dementia. Dermatitis: Dermatitis is found mainly on exposed areas of the body. The changes at first comprise redness, thickening and roughness of the skin, which may be followed by extensive sealing and desquamation, producing fissures and chronic inflammation. Similar lesions may occur in the mucus membranes of the mouth and vagina. Diarrhea: Diarrhea is caused by atrophy of the columnar epithelium of the gastrointestinal track mucosa followed by sub mucosal inflammation. Atrophy may be followed by ulceration. Dementia: Dementia results from degeneration of the neurons in the brain accompanied by degeneration of the corresponding tracts of the spinal cord.

Mineral deficiencies Zinc deficiency

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Basic Pathology: Nutritional diseases

The essential features of zinc deficiency are: 1. A distinctive rash around the eyes, nose, mouth, anus and distal parts 2. Anorexia 3. Growth retardation in children 4. Impaired wound healing 5. Altered immune function 6. An increase incidents of congenital malformations in infants of zinc deficient mothers

Abdullah-Al-Faysal, Lecturer, SUB.