Nutritional Diseases PDF

## OBESITY Obesity is now regarded as a pandemic problem. It is defined as BMI >30 kg/m², and has been further categorized as: - Class I (BMI 30-34.9) - Class II (BMI 35-39.9) - Class III, extreme obesity with BMI beyond 40 People with BMI 25-29.9 are labeled as overweight. ### Causes of Obesit...

## OBESITY Obesity is now regarded as a pandemic problem. It is defined as BMI >30 kg/m², and has been further categorized as: - Class I (BMI 30-34.9) - Class II (BMI 35-39.9) - Class III, extreme obesity with BMI beyond 40 People with BMI 25-29.9 are labeled as overweight. ### Causes of Obesity - Accumulation of fat results from a discrepancy between energy consumption and energy expenditure. - A continuous small daily positive energy balance of only 0.2-0.8 M.J (50-200 kcal; < 10% of intake) would lead to weight gain of 2-20 kg over a period of 4-10 years. - Genetics also play a major role in the development of obesity. - Five genes affecting appetite in mice have been identified. - One gene codes for leptin protein in adipose tissue. Similar genes have been identified in humans. - It is proposed that most of human obesity develops from the interactions of multiple genes, environmental factors, behavior and changes in eating habits. - The rapid increase in obesity in the last several decades points to interplay of all these factors. - It is now estimated that more than 1/4th of adults in USA and UK are obese. The same is more or less true for other developed countries. - The incidence is also on the rise even in developing countries, especially in the cities, due to rapid urbanization, sedentary life styles and changing dietary habits like eating more refined carbohydrates and fast food. ### Clinical Evaluation #### History - It should include the age at which obesity started, family history, recent changes in eating pattern and any changes in personal and psycho-social history. - History should also be obtained regarding any depressive event in the life, sleeping pattern and use of antidepressants and alcohol use. - Attention should also be given to the use of hormones, nutritional supplements, and over the counter medications. #### Physical Examination - Assess the BMI, degree and distribution of body fat, overall nutritional status, and signs of secondary causes of obesity. - Upper body obesity i.e. excess fat around waist and flanks is a more serious health hazard than fat in buttocks and thighs (apple vs pear shape (figure) (fig 12-12). **Fig 12-12. Apple vs Pear distribution of body fat** - Less than 1% of obese patients have an identifiable secondary, non-psychiatric, cause of obesity. - Hypothyroidism and Cushing syndrome are two important causes of secondary obesity and are easily recognizable on clinical examination. The condition can later be confirmed by ordering required hormonal examination. - Also assess for: - Medical complications secondary to obesity and for - Metabolic syndrome. **This includes measurement of blood pressure, waist circumference, fasting glucose, low-density lipoprotein (LDL) and HDL cholesterol, and triglycerides.** #### Complications of Obesity | Complications of Obesity | | :------------------------------------ | | Metabolic syndrome | | Type 2 diabetes, Coronary heart disease | | Hypertension, Stroke, | | Hyperlipidemia, Diabetes complications | | Liver fat accumulation | | Non-alcoholic steatohepatitis (NASH) | | Cirrhosis | | Restricted ventilation | | Exertional dyspnea, | | Sleep apnea syndrome (Pickwickian) | | Mechanical effects of weight | | Urinary incontinence | | Osteoarthritis | | Varicose veins | | Others | | Psychological morbidity (depression) | | Gallstones | | Cancers, esp Colorectal cancer | | Skin infections (groin and submammary) | | Polycystic ovary syndrome | It is suggested that obesity at age 40 years can reduce life expectancy by up to 7 years for non-smokers and by 13 years for smokers. Coronary heart disease is the major cause of death but cancer rates are also increased in the overweight, especially colorectal cancer in males and cancer of the gallbladder, biliary tract, breast, endometrium and cervix in females. Obesity has little effect on life expectancy at > 70 years, but the obese do spend a greater proportion of their active life disabled. ### Treatment The health risks of obesity are largely reversible. Weight loss is associated with a reduction in cardiovascular diseases and the incidence of type 2 diabetes. Most patients seeking assistance with obesity are motivated to lose weight and many have even attempted to lose weight previously and sufficiently motivated patients should enter active treatment programs. Such patients can be identified by requesting a 3-day diet record. Most patients have miscalculated their energy requirements and have inaccurate perceptions of their energy intake. They should be explained that some individuals lose weight faster; hence the others need a greater deficits in energy balance in order to lose and sustain body weight. The management plan therefore has to be individualized with reasonable achievable goals. The common denominator is a decrease in daily calorie content. - A reasonable goal for most patients is to lose 10% of body weight. - A multidisciplinary approach is devised: - Behavior and life style modifications - Change eating behavior and - Maintain weight once reduced - Hypo-caloric diet - Medical treatment (drugs and surgery) **Fig 12-13. Multidisciplinary approach to lose weight** - Behavior and life style modifications - Behavior modification is the corner stone of losing weight. - Current lifestyles with labor saving devices, sedentary work and passive leisure activities have much lower energy requirements than the manual labor and household duties of previous generations. - It is advised that patient should have a: - Regular eating pattern and - Maximize their physical activity - Initiatives include promoting healthy eating in schools, enhancing walking and cycling options for adults while going to offices or to their work. **The food industry should be labeling the foods accurately so as to calculate the energy content of a food. It must be kept in mind that 'low-fat' foods are often still energy-dense and have lots of calories which need to be burnt to avoid weight gain. An important technique in behavior modification is to emphasize planning and record keeping. Regular self-monitoring of weight is also associated with improved long-term weight maintenance.** - Exercise - Aerobic exercise directly increases the daily energy expenditure and is particularly useful for long-term weight maintenance. - Exercise plus diet results in slightly greater weight loss than diet alone. Up to 1 hour of moderate exercise per day is associated with long term weight maintenance in individuals who have successfully lost weight. - Social support is essential for a successful weight loss program. Continued close contact with clinicians and involvement of the family and peer group are useful techniques for reinforcing behavioral change and preventing social isolation. Eating energy rich foods by family members in front of a person trying to lose weight should be avoided. - Weight loss diets Patients with severe obesity need to go on a low calorie intake diet program which may last 4-6 months, even more. Adhering to a diet of 800-1000 kcal/day helps one to lose around 1 kg weight per week. Weight loss is more rapidly achieved with if very-low-calorie diets are taken, but long term outcomes are equivalent. Most important advice is to avoid refined carbohydrates (of all cereals) and replace with vegetable and fruits. Side effects such as fatigue, orthostatic hypotension, cold intolerance, and fluid and electrolyte disorders may occur in these programs, therefore regular checkup is advised. Less common side effects include gout, gallbladder disease, and cardiac arrhythmias. ### Medications - Obesity reducing drugs may be used as an adjunct to diet reduction and behavior modification therapies and not alone. - Orlistat inhibits pancreatic and gastric lipases and thereby decreases the hydrolysis of ingested triglycerides, reducing dietary fat absorption by 1/3rd. The drug is not absorbed and adverse side effects relate to the effect of the resultant fat malabsorption on the gut: namely, loose stools, oily spotting, fecal urgency, flatus and the potential for malabsorption of fat-soluble vitamins. - Orlistat is taken with each of the three main meals of the day and the dose can be adjusted 60-120 mg three times a day. #### Surgery - Bariatric surgery, to reduce the size of the stomach, is by far the most effective long-term treatment for obesity and is the only anti-obesity intervention that has been associated with reduced mortality. - Several approaches are used and all can be performed laparoscopically. - Bariatric surgery should be done in motivated patients who have very high risks of complications of obesity and in whom extensive dietary and drug therapy has been not been effective. - Following procedures are included: - Roux-en-Y gastric bypass (RYGB) - Gastric banding - Sleeve gastrectomy (3/4th stomach resected) - RYGB results in maximum weight loss, even up to 30% but is associated with complications including nutritional deficiencies (iron, vitamin B12, folate, calcium, and vitamin D). Sleeve gastrectomy is hence gaining popularity. ### LIPID DISORDERS - The term lipid includes cholesterol, triglycerides and phospholipids. All three are not soluble in water and are therefore transported by lipoproteins. - Plasma cholesterol and triglycerides are clinically important as they are major treatable risk factors for cardiovascular disease, whilst severe hypertriglyceridemia also predisposes to acute pancreatitis. - Cholesterol is carried primarily on three different lipoproteins in serum i.e. the VLDL, LDL, and HDL molecules. - Total cholesterol equals the sum of these three components: - Total cholesterol = VLDL cholesterol + HDL cholesterol + LDL cholesterol. - Triglycerides, on the other hand, are found mainly in VLDL particles, which contain find times as much triglyceride by weight ve cholesterol. - Plasma lipoprotein levels are major modifiable risk factors for cardiovascular disease. Increased levels of cholesterol carrying lipoproteins are atherogenic, especially LDL. They contribute to the development of atherosclerosis. Increased plasma concentration of these lipoproteins, combined with reduced diameter of blood vessels, favor accumulation of these subendothelial lipoproteins. - Following chemical modifications such as oxidation, these lipoproteins are no longer cleared by normal mechanisms. They trigger a self-perpetuating inflammatory response during which they are taken up by macrophages to form foam cells, a hallmark of atherosclerotic lesions. - HDL removes cholesterol from the tissues to the liver for to be metabolized and excreted in bile. HDL may also reduce inflammation by preventing vascular adhesion of molecules to the endothelium. Therefore low HDL cholesterol levels predispose to atherosclerosis. - There is no true "normal" range for serum lipids. In Western populations, cholesterol values are about 20% higher than in Asian populations. Total and LDL cholesterol levels tend to rise with age in persons who are otherwise in good health. Cholesterol levels do not remain constant over time, especially from childhood through adolescence and young adulthood. Thus, children and young adults with relatively high cholesterol may have lower levels later in life, whereas those with low cholesterol may show increases. - Lipid measurements are usually performed for the following reasons after a 12 hour fast: - Screening for primary or secondary prevention of cardiovascular disease - Investigation of patients with clinical features of lipid disorders - Testing relatives of patients with one of the single gene defects causing dyslipidemia. - Lipid abnormalities may occur in following situations: - Primary disorders - Hypercholesterolemia - Hypertriglyceridemia - Mixed hyperlipidemias - Secondary to medical disorders - Hypothyroidism - Nephrotic syndrome - Diabetes mellitus - Cholestatic liver disease and - Corticosteroid treatment. - Primary lipid disorders are all single gene disorders which interact with environmental factors to produce the disease. - Clinical presentation Most patients with high cholesterol levels have no specific symptoms or signs. The lipid abnormalities are mostly detected by the laboratory, either as part of the workup of a patient with cardiovascular disease, diabetes or as part of a preventive screening strategy. - Extremely high levels of chylomicrons or VLDL particles (triglyceride level above 1000 mg/dL) result in the formation of eruptive xanthomas (red-yellow papules, especially on the buttocks). - High LDL concentrations result in tendon xanthomas on certain tendons (Achilles, patella, back of the hand) (fig 12-14). Such xanthomas usually indicate one of the underlying genetic hyperlipidemias. - Lipemia retinalis (cream-colored blood vessels in the fundus) is seen with extremely high triglyceride levels (above 2000 mg/dL). - Xanthelasma, yellow plaques on eye lids (fig 12-15), are common occurrence, but are nonspecific. **Fig 12-14. Eruptive xanthomas and tendon xanthoma on the back of elbow. (Courtesy Dr. Gary White, http://www.regionalderm.com/index.html)** **Fig 12-15. Xanthelasma around eyelids. (Courtesy Dr. Gary White, http://www.regionalderm.com/index.html)** ### TREATMENT The main aim of treating hyperlipidemias is to reduce the risk of cardiovascular diseases. - Various assessment methods have been devised for estimating overall risk for the development of cardiovascular disease of a patient in the next 10 years. The factors usually studied are age, sex, total cholesterol, HDL and smoking. - Patients 10 year risk is calculated by counting the total number of points scored. - Patients with low risk of developing cardiovascular diseases are advised: - Life style modifications and - Diet therapy, - Patients with high risk are advised: - Life style modifications - Diet therapy - Drugs - In general, patients who already have cardiovascular disease, diabetes mellitus, CKDLDL >190 mg/dl, or an absolute risk of cardiovascular disease of greater than 20% in the ensuing 10 years are regarded the candidates for the drug therapy. - Diet and life style modification - Dietary instructions include: - Reduce intake of total fats to 25-30% and saturated fats to less than 7-10% of total energy - Reduce intake of cholesterol to < 200 mg/day - Replace sources of saturated fat and cholesterol with alternative foods such as lean meat, low-fat dairy products and low glycemic index carbohydrates. This results in fewer total calories overall and facilitates weight loss in overweight. - Reduce energy rich foods like refined carbohydrates, fast food, fats and soft drinks and encourage physical activity and exercise to maintain or lose weight - Increase consumption of cardioprotective foods such as vegetables, unrefined carbohydrates, fish, pulses, nuts, legumes, fruit etc. - Reduce / stop alcohol consumption - Increase the intake of foods containing lipid. lowering nutrients such as n-3 fatty acids, dietary fiber and plant sterols. - Response to diet is usually apparent within 3-4 weeks. Hyperlipidemia in general and hypertriglyceridemia respond in a much better way while LDL-C reductions are often modest (5-10%). The effect of diet therapy, however, varies considerably among individuals, as some patients may have striking reductions in LDL cholesterol up to a 25-30%. In addition to the generalized dietary advices described above there are some other diet plans: - A total vegetarian diet plan which almost totally restricts fats and leads to a further reduction in total cholesterol, but this may also lead to a reduction in HDL as well. - Mediterranean diet, which maintains total fat at approximately 30-35% of total calories but replaces saturated fat with monounsaturated fat such as that found in canola oil and in olives, peanuts, avocados, and their oils. This diet is equally effective at lowering LDL cholesterol but is less likely to lead to reductions in HDL cholesterol. Several studies have suggested that this approach may also be associated with reductions in endothelial dysfunction, insulin resistance, and markers of vascular inflammation and may result in better resolution of the metabolic syndrome than traditional cholesterol lowering diets. - Other dietary changes include soluble fiber such as that found in oat bran or Psyllium. - Garlic, soy protein, vitamin C, pecans, and plant sterols may also result in reduction of LDL cholesterol. - Diets rich in antioxidants, found primarily in fruits and vegetables, may be helpful by preventing oxidation of LDL cholesterol which usually triggers atherosclerosis. ### Drug therapy - Hypercholesterolemia: Following group of drugs are used for hypercholesterolemia: - HMG-CoA reductase inhibitors i.e. Statins - Cholesterol absorption inhibitors i.e. Ezetimibe - Bile acid binding resins i.e. cholestyramine - Nicotinic acid (Niacin) - Statins are HMG-CoA reductase inhibitors and act by inhibiting the rate limiting enzyme in the synthesis of cholesterol. They reduce MI and overall mortality in secondary prevention. They also reduce the risk of stroke. All those patients who need drug treatment are put on Statins as a first line drug. The ACC/AHA guidelines define four groups of patients who benefit from statins: - Individuals clinically suffering from IHD due to atherosclerosis - LDL cholesterol greater than 190 mg/dL - Individuals aged 40-75 with diabetes and LDL greater than or equal to 70 mg/dL - Individuals aged 40-75 without diabetes, LDL 70-189mg/dL and CVD risk in next 10 years >7.5%. - Statins are divided into 2 groups; high and moderate intensity statins. High intensity statins lower LDL cholesterol by 50% e.g. atorvastatin 40-80 mg and rosuvastatin 20-40 mg. Moderate intensity statins lower LDL cholesterol by 30-50% e.g. atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin 20-40 mg, pravastatin 40-80 mg, and lovastatin 40 mg. - Side effects are muscle aches (10% patients) and mild gastrointestinal effects. Statins are associated with a 10% increase in the risk of diabetes. Some rare side effects include liver failure and myositis and rhabdomyolysis. Keeping this in mind LFT's are recommended before the start of therapy. - If desired effects of lowering cholesterol are not achieved, statins can be combined with the following drugs. These drugs can be given independently in cases where statins are intolerable to the patient. - Ezetimibe inhibits the intestinal absorption of dietary and biliary cholesterol by blocking passage across the intestinal wall by inhibiting a cholesterol transporter. The usual dose of ezetimibe is 10 mg/day orally. Ezetimibe reduces LDL cholesterol by 15% to 20% and when combined with statins they cause further reduction in cholesterol. The long term effect of ezetimibe on cardiovascular disease is not yet known. - Cholestyramine and other bile acids binding resins (colestipol, colesevelam) work by binding bile acid in the intestine. This causes a reduction in the pool of bile acids, liver compensates by increasing the production of new bile acid and hence using up hepatic cholesterol pool. Use of these resins in associated with a decrease in the incidence of MI but no decrease in overall mortality. The usual dosage is 12-36 g/day in divided doses. The usual side effects are Gl upsets, gas and constipation. These agents reduce the absorption of fat soluble vitamin and can also interfere with the absorption of other drugs. Resins are safe to use in pregnancy. - Nicotinic acid reduces the production of VLDL, thereby causing a secondary reduction in LDL and increases HDL. Niacin also reduces triglycerides. Side effects are common and most people can't tolerate a full dose. Niacin causes prostaglandin mediated flushing and pruritus. ### 2. Treatment for predominant hypertriglyceridemia - The primary therapy for high triglyceride levels is dietary. The patients are advised to decrease their overall calories. They are also advised against taking simple sugars, refined starches, saturated and trans-fatty acids, and restricting alcohol. - Patients with triglyceride levels above 500mg/dL or those who have had an episode of pancreatitis in past drug therapy is indicated. Drug therapy includes the use of fibric acid derivates (fibrates) like gemfibrozil, nicotinic acid and omega-3-acid ethyl esters. Omega-3 are fish oils and an intake of more than 2g/day lower the triglyceride levels. If needed a statin may also be used to reduce TG levels. These drugs can be given alone or in combination as well. ### PROTEIN ENERGY MALNUTRITION (PEM) - Protein-energy malnutrition occurs as a result of a relative or absolute deficiency of energy and protein. It may be primary, due to inadequate food intake, or secondary, as a result of other illness. - Primary protein energy malnutrition remains a significant health problem in developing countries. It occurs in two distinct syndromes (fig 12-16). - Kwashiorkor is caused by a deficiency of protein in the presence of adequate energy available from other foods. It is typically seen in weaning infants at the birth of a sibling. The diet of these weaned infants is replaced by carbohydrate rich and protein deficient diet. - Marasmus is caused by combined protein and energy deficiency, is seen where adequate quantities of food are simply not available. - **Fig12-16. Marasmus vs kwashiorkor** - In industrialized countries secondary from of protein energy malnutrition occurs due to presence of other diseases. - Kwashiorkor like secondary PEM can occur in hypermetabolic acute diseases like sepsis, burns or trauma. - Marasmus like secondary PEM can occur in chronic diseases like COPD, CCF and cancer. In both types of PEM the deficiency occurs both due to decreased intake or increased nutrient loss. ### Clinical Findings - Clinical manifestations of protein energy malnutrition range from mild growth retardation and weight loss to a number of distinct clinical syndromes like kwashiorkor and marasmus. - In marasmus there is a progressive weight loss and may proceed to severe cachexia. In severe cases most of the body fat stores disappear and muscle mass decreases, most noticeably in the temporalis and interosseous muscles. Laboratory studies may be unremarkable. Serum albumin may be slightly decreased (up to 2.8g/dl). In contrast, owing to its rapidity of onset, kwashiorkor like malnutrition may develop in patients with normal subcutaneous fat and muscle mass. The serum protein level however declines and the serum albumin is often less than 2.8 g/dL (28 g/L). Dependent edema, ascites, or anasarca may develop. As with primary protein-energy malnutrition, combinations of the marasmus-like and kwashiorkor-like syndromes can occur simultaneously, typically in patients with progressive chronic disease in whom superimposed acute illness develops. ### Treatment: - The treatment of severe protein energy malnutrition is a slow process requiring great care. Initial efforts should be directed at correcting fluid and electrolyte abnormalities and infections. Of particular concern are depletion of potassium, magnesium, and calcium and acid base abnormalities. - The second phase of treatment is directed at repletion of energy, protein, and micronutrients. Treatment is started with modest quantities of protein and calories calculated based on the patient's actual body weight. Adult patients are given 1 g/kg of protein and 30 kcal/kg of calories. Concomitant administration of vitamins and minerals is necessary. It is preferable to use the enteral route, though parenteral route can be used if needed. Patients with less severe malnutrition can be given calories and protein simultaneously with the correction of fluid and electrolyte abnormalities. - Patients who are re-fed too rapidly may develop a number of untoward clinical sequelae, including electrolyte imbalances, diarrhea and even heart failure if excess fluid is administered. ### VITAMIN DEFICIENCIES : - Vitamin deficiency diseases are most prevalent in developing countries, but can occur in certain populations of developed countries e.g. elderly, alcoholics and patients with GIT and liver disorders. Nutritional deficiencies are also common in pregnancy, again more so in developing world, and can affect both mother and the developing fetus. Some vitamins also have pharmacological actions when given at supra-physiological doses, e.g. the use of vitamin A for acne. Vitamins have no caloric value but many patients regard them as 'energy medicines'. Hence taking vitamin supplements has become fashionable in many countries, although there is no evidence of benefit. They should be prescribed when needed according to the clinical condition and biochemical assessment. Injudicious use may even cause toxic effects, especially following high doses of vitamins A, B6 and D. ### THIAMINE (B1) DEFICIENCY (Beri-Beri) - Worldwide the biggest cause of thiamine deficiency is alcoholism along with poor diet. The body has very limited stores of thiamine, so deficiency is manifested after only 1 month on a thiamine-free diet. Thiamine deficiency can also occur secondary to malabsorption and liver disorders. Thiamine deficiency can be precipitated in patients with marginal thiamine status when given intravenous dextrose infusions, a practice quite common in developing countries. The clinical feature of the deficiency occur due to two reasons: - In thiamine deficiency aerobic **metabolism of the glucose gets impaired, hence neuronal cells are affected most and leads to their inability to generate ATP. The neurological form is called as 'dry beri-beri'.** - **Impaired glucose oxidation also causes an accumulation of pyruvic and lactic acids, which produce vasodilatation and increased cardiac output causing high output failure (wet beri-beri). Due to vasodilatation extremities remain warm.** - There clinical manifestations include: - Dry beri-beri - Chronic peripheral neuropathy with wrist and/or foot drop, - Korsakoff's psychosis and - Wernicke's encephalopathy - Wet beri-beri (features of CCF): - Generalized edema - Pulmonary edema - SOB - Orthopnea/PND - Wernicke-korsakoff syndrome - Nystagmus - Opthalmoplegia - Ataxia - Confusion and amnesia - Diagnosis - In most instances, the clinical response to empiric thiamine therapy is used to support a diagnosis of thiamine deficiency. A transketolase activity coefficient greater than 15-20% in erythrocytes suggests thiamine deficiency. - Treatment - Wernicke's encephalopathy and wet beri-beri should be treated without delay with intravenous Bl. Fifty to 100 mg/day is administered intravenously for the first few days, followed by daily oral doses of 5-10 mg/day. All patients should simultaneously receive therapeutic doses of other water-soluble vitamins. - Korsakoff's psychosis is irreversible and does not respond to thiamine treatment. - There is no toxicity of thiamine. ### Riboflavin (B2) deficiency - Riboflavin (B2) deficiency occurs along with other vitamin deficiencies. - Manifestations of riboflavin deficiency include cheilosis, angular stomatitis, glossitis, seborrheic dermatitis, weakness and anemia. - The deficiency is treated by giving foods such as meat, fish, and dairy products or with oral preparations of the vitamin. Rapid recovery usually follows administration of riboflavin. ### NIACIN (NICOTINIC ACID) B3 (Pellagra) - It is an essential component of co-enzyme nicotinamide adenine dinucleotide (NAD). - Niacin can be synthesized by amino acid tryptophan. It is present in proteins containing tryptophan, dairy products, vegetables and cereals. - Pellagra was formerly endemic among the poor whose staple diet was mainly maize, which contains niacytin, a form of niacin that the body cannot utilize. The disease is still a problem in some parts of Africa, malabsorption patients and alcoholics. - Pellagra can develop in only 8 weeks in individuals eating diets that are very deficient in niacin and tryptophan. - Mild deficiency causes anorexia, weakness, irritability, mouth soreness, glossitis, stomatitis, and weight loss. Severe deficiency causes a triad of 3 D's called as Pellagra: - Dermatitis - Diarrhea, and - Dementia - The dermatitis is symmetric, involving sun-exposed areas but sparing face (casal's necklace). Skin lesions are dark, dry, and scaling. The dementia begins with insomnia, irritability, and apathy and progresses to confusion, memory loss, hallucinations, and psychosis. The diarrhea can be severe and may result in malabsorption due to atrophy of the intestinal villi. Advanced pellagra can result in death. - Treatment is with nicotinamide, both oral and parenteral forms are available. Excessive use can cause toxicity, especially hepatic. Nicotinic acid is a lipid-lowering agent, but at doses above 200mg a day gives rise to vasodilatory symptoms ('flushing' and/or hypotension). ### VITAMIN B, DEFICIENCY - Vitamin B6 deficiency most commonly occurs as a result of interactions with medications, especially isoniazid, cycloserine, penicillamine, and oral contraceptives. It can also occur in alcoholism. - Clinical Features Vitamin B6 deficiency results in clinical symptoms similar to those of other B vitamin deficiencies, including mouth soreness, glossitis, cheilosis, weakness, and irritability. Severe deficiency can result in peripheral neuropathy, anemia, and seizures. - Diagnosis The diagnosis of vitamin B6 deficiency can be confirmed by measurement of pyridoxal phosphate in blood. Normal levels are greater than 50 ng/mL. ### Treatment: - Vitamin B6 deficiency can be effectively treated by giving the vitamin orally (10-20 mg/day). Patients taking medications like isoniazid may need doses as high as 50-100 mg/day orally. - Patients taking high doses of vitamin B6 may develop toxicity in the form of irreversible neuropathy. ### VITAMIN C DEFICIENCY (SCURVY) (Ascorbic acid) - Vitamin C deficiency causes defective formation of collagen with impaired healing of wounds, capillary hemorrhage and reduced platelet adhesiveness (normal platelets are rich in ascorbate). - As with most of other vitamins, deficiency occurs due to dietary inadequacy or due to alcoholism. Deficiency can occur in individuals who do not take fruits or vegetables for more than 2 months. Early manifestations of vitamin C deficiency are nonspecific and include malaise and weakness. In more advanced stages, the typical features of scurvy develop. Manifestations include: - Perifollicular hemorrhages, - Petechiae and purpura. - Bleeding from gums is an important feature (fig 12-17). - Hemarthrosis may also occur. - Anemia is common - Wound healing is impaired. - In late stages scurvy can cause edema, oliguria, neuropathy, intracerebral hemorrhage and death. **Fig 12-17. Bleeding and hyperplastic gums in scurvy** - The diagnosis can be made clinically in most cases and can be confirmed by low plasma levels of ascorbic acid. - Treatment consists of oral vitamin C 300- 1000 mg/day. Excessive doses of vitamin C can cause diarrhea and the formation of renal oxalate stones. ### VITAMIN A DEFICIENCY - Globally, the most important consequence of vitamin A deficiency is blindness, especially in young malnourished children of Asia. Adults are not usually at risk because of liver stores of vitamin A, but deficiency in adults can occur following malabsorption of fats. The clinical features include: - Night blindness is the earliest symptom. - Dryness of the conjunctiva (xerosis) - Bitot spots (small white patches on the conjunctiva). - Ulceration and necrosis of the cornea (keratomalacia), - Perforation of cornea - Endophthalmitis, and - Blindness - Skin findings are: - Xerosis and - Hyperkeratinization of the skin - Poor wound healing, and - loss of taste may also occur. - Diagnosis is strongly suggested if someone is unable to see in the dark. Serum levels below the normal range of 30-65 mg/dL are commonly seen in advanced deficiency. ### Treatment: - Night blindness, poor wound healing, and other signs of early deficiency can be effectively treated with vitamin A 30,000 international units orally daily for 1 week. Advanced deficiency may need increased doses for initial few days. ### Prevention: - In countries where vitamin A deficiency is endemic, pregnant women should be advised to eat dark green leafy vegetables and yellow liver), and infants should be fed the same. - WHO advises single oral dose of 60mg retinyl palmitate to preschool children in countries with high incidence of xeropthalmia. This also reduces mortality from gastroenteritis and respiratory infections. - Vitamin A toxicity Chronic ingestion of daily doses of over 50,000 international units/day for more than 3 months can lead to hypervitaminosis A. which can be quite toxic and is teratogenic. Early manifestations include dry, scaly skin, hair loss, mouth sores, painful hyperostoses, anorexia, and vomiting. Later hypercalcemia may occur with increased intracranial pressure, papilledema, headaches, and decreased cognition. The condition is teratogenic. Acute toxicity can result from ingestion of massive doses of vitamin A, such as in drug overdoses. Manifestations include nausea, vomiting, abdominal pain, headache, papilledema, and lethargy. Excess intake of beta-carotenes (hypercarotenosis) results in staining of the skin a yellow-orange color but is otherwise benign. It differs from jaundice as the scleras remain white. The diagnosis can be confirmed by elevations of serum vitamin A levels. The only treatment is withdrawal of vitamin A from the diet. Most symptoms and signs improve rapidly. ### Vitamin E - Clinical deficiency of vitamin E is most commonly due to severe malabsorption or chronic cholestatic liver disease, biliary atresia, or cystic fibrosis in children. Manifestations of deficiency include cramps, disturbances of gait, decreased vibration and proprioception, depressed reflexes and ophthalmoplegia. Plasma vitamin E levels can be measured and are depressed. Treatment consists of giving oral preparations. If needed larger doses can be given parenterally. Large doses of vitamin E given for longer period of time can result in an increase in all cause mortality rates. - Randomized controlled trials have not demonstrated cardioprotective effects of vitamin E or other antioxidants. ### Vitamin K - Vitamin K deficiency leads to delayed coagulation and bleeding. In obstructive jaundice, dietary vitamin K is not absorbed and it is essential to administer the vitamin in parenteral form before surgery. Warfarin and related anticoagulants act by antagonizing vitamin K. - Vitamin K is given routinely to newborn babies to prevent hemorrhagic disease. ### Vitamin D - The effects of vitamin D deficiency include: - Calcium deficiency - Rickets and - Osteomalacia These diseases are discussed elsewhere. Treatment consists of various forms of vitamin D. Excessive doses of cholecalciferol, ergocalciferol or the hydroxylated metabolites cause hypercalcemia. ### Vitamin B12 and Folic acid - The deficiency of these vitamins causes hematological and neurological disorders: - Megaloblastic anemia - Subacute combined degeneration of cord - Neuropathies - Folate deficiency in addition has major consequences on fetus, causing three major birth defects: - Spina bifida, - Anencephaly and - Encephalocele resulting from imperfect closure of the neural tube, which takes place 3-4 weeks after conception. Maternal supplements with folate reduces the risk - Folate deficiency has also been associated with heart disease, dementia and cancer. Both are discussed in chapter on blood diseases. ### Biotin - Biotin deficiency is very rare. It may occur following consumption of large amounts of egg white or after prolonged TPN. The clinical features of deficiency include scaly dermatitis, alopecia and paresthesia.