# migrations

dir: embeddings_queue
filename: 00001-embeddings.sqlite.sql
hash: d3755dfd232be8e8301f4d7fcfb3a486
sql:
CREATE TABLE embeddings_queue (
    seq_id INTEGER PRIMARY KEY,
    created_at TIMESTAMP NOT NULL DEFAULT CURRENT_TIMESTAMP,
    operation INTEGER NOT NULL,
    topic TEXT NOT NULL,
    id TEXT NOT NULL,
    vector BLOB,
    encoding TEXT,
    metadata TEXT
);


dir: sysdb
filename: 00001-collections.sqlite.sql
hash: 38352d725ad1c16074fac420b22b4633
sql:
CREATE TABLE collections (
    id TEXT PRIMARY KEY,
    name TEXT NOT NULL,
    topic TEXT NOT NULL,
    UNIQUE (name)
);

CREATE TABLE collection_metadata (
    collection_id TEXT REFERENCES collections(id) ON DELETE CASCADE,
    key TEXT NOT NULL,
    str_value TEXT,
    int_value INTEGER,
    float_value REAL,
    PRIMARY KEY (collection_id, key)
);


dir: sysdb
filename: 00002-segments.sqlite.sql
hash: 2913cb6a503055a95f625448037e8912
sql:
CREATE TABLE segments (
    id TEXT PRIMARY KEY,
    type TEXT NOT NULL,
    scope TEXT NOT NULL,
    topic TEXT,
    collection TEXT REFERENCES collection(id)
);

CREATE TABLE segment_metadata (
    segment_id TEXT  REFERENCES segments(id) ON DELETE CASCADE,
    key TEXT NOT NULL,
    str_value TEXT,
    int_value INTEGER,
    float_value REAL,
    PRIMARY KEY (segment_id, key)
);


dir: sysdb
filename: 00004-tenants-databases.sqlite.sql
hash: 048867ce8fcdefe4023c7110e4433591
sql:
CREATE TABLE IF NOT EXISTS tenants (
    id TEXT PRIMARY KEY,
    UNIQUE (id)
);

CREATE TABLE IF NOT EXISTS databases (
    id TEXT PRIMARY KEY, -- unique globally
    name TEXT NOT NULL, -- unique per tenant
    tenant_id TEXT NOT NULL REFERENCES tenants(id) ON DELETE CASCADE,
    UNIQUE (tenant_id, name) -- Ensure that a tenant has only one database with a given name
);

CREATE TABLE IF NOT EXISTS collections_tmp (
    id TEXT PRIMARY KEY, -- unique globally
    name TEXT NOT NULL, -- unique per database
    topic TEXT NOT NULL,
    dimension INTEGER,
    database_id TEXT NOT NULL REFERENCES databases(id) ON DELETE CASCADE,
    UNIQUE (name, database_id)
);

-- Create default tenant and database
INSERT OR REPLACE INTO tenants (id) VALUES ('default_tenant'); -- The default tenant id is 'default_tenant' others are UUIDs
INSERT OR REPLACE INTO databases (id, name, tenant_id) VALUES ('00000000-0000-0000-0000-000000000000', 'default_database', 'default_tenant');

INSERT OR REPLACE INTO collections_tmp (id, name, topic, dimension, database_id)
    SELECT id, name, topic, dimension, '00000000-0000-0000-0000-000000000000' FROM collections;
DROP TABLE collections;
ALTER TABLE collections_tmp RENAME TO collections;


dir: sysdb
filename: 00005-remove-topic.sqlite.sql
hash: b1367c826b8fba5f96f27befdc1d42d2
sql:
-- Remove the topic column from the Collections and Segments tables

ALTER TABLE collections DROP COLUMN topic;
ALTER TABLE segments DROP COLUMN topic;


dir: sysdb
filename: 00006-collection-segment-metadata.sqlite.sql
hash: 4eea7468935bf25d4604a0fed2366116
sql:
-- SQLite does not support adding check with alter table, as a result, adding a check
-- involve creating a new table and copying the data over. It is over kill with adding
-- a boolean type column. The application write to the table needs to ensure the data
-- integrity.
ALTER TABLE collection_metadata ADD COLUMN bool_value INTEGER;
ALTER TABLE segment_metadata ADD COLUMN bool_value INTEGER;


dir: metadb
filename: 00001-embedding-metadata.sqlite.sql
hash: 2b4cf52c4bb2676e21d6860a4409f856
sql:
CREATE TABLE embeddings (
    id INTEGER PRIMARY KEY,
    segment_id TEXT NOT NULL,
    embedding_id TEXT NOT NULL,
    seq_id BLOB NOT NULL,
    created_at TIMESTAMP NOT NULL DEFAULT CURRENT_TIMESTAMP,
    UNIQUE (segment_id, embedding_id)
);

CREATE TABLE embedding_metadata (
    id INTEGER REFERENCES embeddings(id),
    key TEXT NOT NULL,
    string_value TEXT,
    int_value INTEGER,
    float_value REAL,
    PRIMARY KEY (id, key)
);

CREATE TABLE max_seq_id (
    segment_id TEXT PRIMARY KEY,
    seq_id BLOB NOT NULL
);

CREATE VIRTUAL TABLE embedding_fulltext USING fts5(id, string_value);


dir: metadb
filename: 00002-embedding-metadata.sqlite.sql
hash: 12a570f7121b3a8ce750a2a7c36da20f
sql:
-- SQLite does not support adding check with alter table, as a result, adding a check
-- involve creating a new table and copying the data over. It is over kill with adding
-- a boolean type column. The application write to the table needs to ensure the data
-- integrity.
ALTER TABLE embedding_metadata ADD COLUMN bool_value INTEGER


dir: metadb
filename: 00003-full-text-tokenize.sqlite.sql
hash: f97ad6334aeaa8f419f01110b648b97a
sql:
CREATE VIRTUAL TABLE embedding_fulltext_search USING fts5(string_value, tokenize='trigram');
INSERT INTO embedding_fulltext_search (rowid, string_value) SELECT rowid, string_value FROM embedding_metadata;
DROP TABLE embedding_fulltext;


# embeddings_queue

created_at: 2025-06-20 08:54:40
topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
id: 2f027411-2fe4-4187-849e-65f080e2fc3e
encoding: FLOAT32
metadata:
{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 0, "chroma:document": "1 - Nutritional Disorders\nChapter 1. Nutrition: General Considerations\nIntroduction\nNutrition is the science of food and its relationship to health. Nutrients are chemicals in foods that are\nused by the body for growth, maintenance, and energy. Nutrients that cannot be synthesized by the body\nand thus must be derived from the diet are considered essential. They include vitamins, minerals, some\namino acids, and some fatty acids. Nutrients that the body can synthesize from other compounds,\nalthough they may also be derived from the diet, are considered nonessential. Macronutrients are\nrequired by the body in relatively large amounts; micronutrients are needed in minute amounts.\nLack of nutrients can result in deficiency syndromes (eg, kwashiorkor, pellagra) or other disorders (see p.\n9\n). Excess intake of macronutrients can lead to obesity (see p. \n56\n) and related disorders; excess intake of\nmicro-nutrients can be toxic. Also, the balance of various types of nutrients, such as how much\nusaturated vs saturated fat is consumed, can influence the development of disorders.\nMacronutrients\nMacronutrients constitute the bulk of the diet and supply energy and many essential nutrients.\nCarbohydrates, proteins (including essential amino acids), fats (including essential fatty acids),\nmacrominerals, and water are macronutrients. Carbohydrates, fats, and proteins are interchangeable as\nsources of energy; fats yield 9 kcal/g (37.8 kJ/g); proteins and carbohydrates yield 4 kcal/g (16.8 kJ/g).\nCarbohydrates:\n Dietary carbohydrates are broken down into glucose and other monosaccharides.\nCarbohydrates increase blood glucose levels, supplying energy. Simple carbohydrates are composed of\nsmall molecules, generally monosaccharides or disaccharides, which increase blood glucose levels\nrapidly. Complex carbohydrates are composed of larger molecules, which are broken down into\nmonosaccharides. Complex carbohydrates increase blood glucose levels more slowly but for a longer\ntime. Glucose and sucrose are simple carbohydrates; starches and fiber are complex carbohydrates.\nThe glycemic index measures how rapidly consumption of a carbohydrate increases plasma glucose\nlevels. Values range from 1 (the slowest increase) to 100 (the fastest increase, equivalent to pure glucose\n\u2014see\nTable 1-1\n). However, the actual rate of increase also depends on what foods are consumed with the\ncarbohydrate.\nCarbohydrates with a high glycemic index may increase plasma glucose to high levels rapidly. It is\nhypothesized that, as a result, insulin levels increase, inducing hypoglycemia and hunger, which tends to\nlead to consumption of excess calories and weight gain. Carbohydrates with a low glycemic index\nincrease plasma glucose levels slowly, resulting in lower postprandial insulin levels and less hunger,\nwhich probably makes consumption of excess calories less likely. These effects are predicted to result in\na more favorable lipid profile and a decreased risk of obesity, diabetes mellitus, and complications of\ndiabetes if present.\nProteins:\n Dietary proteins are broken down into peptides and amino acids. Proteins are required for\ntissue maintenance, replacement, function, and growth. However, if the body is not getting enough\ncalories from dietary sources or tissue stores (particularly of fat), protein may be used for energy.\nAs the body uses dietary protein for tissue production, there is a net gain of protein (positive nitrogen\nbalance). During catabolic\n[\nTable 1-1.\n Glycemic Index of Some Foods]\nstates (eg, starvation, infections, burns), more protein may be used (because body tissues are broken\ndown) than is absorbed, resulting in a net loss of protein (negative nitrogen balance). Nitrogen balance is\nbest determined by subtracting the amount of nitrogen excreted in urine and feces from the amount of\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 1. Nutrition: General Considerations\n53"}


created_at: 2025-06-20 08:54:40
topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
id: c0699ef7-6ab6-4120-a20d-ab46988f4638
encoding: FLOAT32
metadata:
{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 1, "chroma:document": "nitrogen consumed.\nOf the 20 amino acids, 9 are essential amino acids (EAAs); they cannot be synthesized and must be\nobtained from the diet. All people require 8 EAAs; infants also require histidine.\nThe weight-adjusted requirement for dietary protein correlates with growth rate, which decreases from\ninfancy until adulthood. The daily dietary protein requirement decreases from 2.2 g/kg in 3-mo-old infants\nto 1.2 g/kg in 5-yr-old children and to 0.8 g/kg in adults. Protein requirements correspond to EAA\nrequirements (see\nTable 1-2\n). Adults trying to increase muscle mass need very little extra protein beyond the requirements in\nthe table.\nThe amino acid composition of protein varies widely. Biological value (BV) reflects the similarity in amino\nacid composition of protein to that of animal tissues; thus, BV indicates what percentage of a dietary\nprotein provides EAAs for the body. A perfect match is egg protein, with a value of 100. Animal proteins in\nmilk and meat have a high BV (~90); proteins in cereal and vegetables have a lower BV (~40), and some\nderived proteins (eg, gelatin) have a BV of 0. The extent to which dietary proteins supply each other's\nmissing amino acids (complementarity) determines the overall BV of the diet. The recommended daily\nallowances (RDA) for protein assumes that the average mixed diet has a BV of 70.\nFats:\n Fats are broken down into fatty acids and glycerol. Fats are required for tissue growth and hormone\nproduction. Saturated fatty acids, common in animal fats, tend to be solid at room temperature. Except for\npalm and coconut oils, fats derived from plants tend to be liquid at room temperature; these fats contain\nhigh levels of monounsaturated fatty acids or polyunsaturated fatty acids (PUFAs).\nPartial hydrogenation of unsaturated fatty acids (as occurs during food manufacturing) produces trans\nfatty acids, which are solid or semisolid at room temperature. In the US, the main dietary source of trans\nfatty acids is partially hydrogenated vegetable oils, used in manufacturing certain foods (eg, cookies,\ncrackers, chips) to prolong shelf-life. Trans fatty acids may elevate LDL cholesterol and lower HDL; they\nmay also independently increase the risk of coronary artery disease.\nEssential fatty acids (EFAs) are linoleic acid, an \n\u03c9\n-6 (n-6) fatty acid, and linolenic acid, an \n\u03c9\n-3 (n-3) fatty\nacid. Other \n\u03c9\n-6 acids (eg, arachidonic acid) and other \n\u03c9\n-3 fatty acids (eg, eicosapentaenoic acid,\ndocosahexaenoic acid) are required by the body but can be synthesized from EFAs.\nEFAs (see also p. \n19\n) are needed for the formation of various eicosanoids (biologically active lipids),\nincluding prostaglandins, thromboxanes, prostacyclins, and leukotrienes. Consumption of \n\u03c9\n-3 fatty acids\nmay decrease the risk of coronary artery disease.\n[\nTable 1-2.\n Essential Amino Acid Requirements in mg/kg Body Weight]\nRequirements for EFAs vary by age. Adults require amounts of linoleic acid equal to at least 2% of total\ncaloric needs and linolenic acid equal to at least 0.5%. Vegetable oils provide linoleic acid and linolenic\nacid. Oils made from safflower, sunflower, corn, soya, primrose, pumpkin, and wheat germ provide large\namounts of linoleic acid. Marine fish oils and oils made from flax-seeds, pumpkin, soy, and canola provide\nlarge amounts of linolenic acid. Marine fish oils also provide some other \n\u03c9\n-3 fatty acids in large amounts.\nMacrominerals:\n Na, Cl, K, Ca, P, and Mg are required in relatively large amounts per day (see\nTables 1-3\n,\n1-4\n, and\n5-2\n).\nWater:\n Water is considered a macronutrient because it is required in amounts of 1 mL/kcal (0.24 mL/kJ)\nof energy expended, or about 2500 mL/day. Needs vary with fever, physical activity, and changes in\nclimate and humidity.\n[\nTable 1-3.\n Macrominerals]\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 1. Nutrition: General Considerations\n54"}


created_at: 2025-06-20 08:54:40
topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
id: d1537dd0-f739-4906-836d-79cc6a6a20ba
encoding: FLOAT32
metadata:
{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 2, "chroma:document": "[\nTable 1-4.\n Recommended Dietary Reference Intakes* for Some Macronutrients, Food and Nutrition\nBoard, Institute of Medicine of the National Academies]\nMicronutrients\nVitamins and minerals required in minute amounts (trace minerals) are micronutrients (see \nChs. 4\n and \n5\n).\nWater-soluble vitamins\n are vitamin C (ascorbic acid) and 8 members of the vitamin B complex: biotin,\nfolate, niacin, pantothenic acid, riboflavin (vitamin B\n2\n), thiamin (vitamin B\n1\n), vitamin B\n6\n (pyridoxine), and\nvitamin B\n12\n (cobalamin).\nFat-soluble vitamins\n are vitamins A (retinol), D (cholecalciferol and ergocalciferol), E (\n\u03b1\n-tocopherol), and\nK (phylloquinone and menaquinone).\nOnly vitamins A, E, and B\n12\n are stored to any significant extent in the body; the other vitamins must be\nconsumed regularly to maintain tissue health.\nEssential trace minerals\n include chromium, copper, iodine, iron, manganese, molybdenum, selenium,\nand zinc. Except for chromium, each of these is incorporated into enzymes or hormones required in\nmetabolism. Except for deficiencies of iron and zinc, micromineral deficiencies are uncommon in\ndeveloped countries (see \nCh. 5\n).\nOther minerals (eg, aluminum, arsenic, boron, cobalt, fluoride, nickel, silicon, vanadium) have not been\nproved essential for people. Fluoride, although not essential, helps prevent tooth decay by forming a\ncompound with Ca (CaF\n2\n), which stabilizes the mineral matrix in teeth.\nAll trace minerals are toxic at high levels, and some (arsenic, nickel, and chromium) may cause cancer.\nOther Dietary Substances\nThe daily human diet typically contains as many as 100,000 chemicals (eg, coffee contains 1000). Of\nthese, only 300 are nutrients, only some of which are essential. However, many nonnutrients in foods are\nuseful. For example, food additives (eg, preservatives, emulsifiers, antioxidants, stabilizers) improve the\nproduction and stability of foods. Trace components (eg, spices, flavors, odors, colors, phytochemicals,\nmany other natural products) improve appearance and taste.\nFiber:\n Fiber occurs in various forms (eg, cellulose, hemicellulose, pectin, gums). It \nincreases GI motility,\nprevents constipation, and helps control diverticular disease. Fiber is thought to accelerate the elimination\nof cancer-causing substances produced by bacteria in the large intestine. Epidemiologic evidence\nsuggests an association between colon cancer and low fiber intake and a beneficial effect of fiber in\npatients with functional bowel disorders, Crohn's disease, obesity, and hemorrhoids. Soluble fiber\n(present in fruits, vegetables, oats, barley, and legumes) reduces the postprandial increase in blood\nglucose and insulin and can reduce cholesterol levels.\nThe typical Western diet is low in fiber (about 12 g/day) because of a high intake of highly refined wheat\nflour and a low intake of fruits and vegetables. Increasing fiber intake to about 30 g/day by consuming\nmore vegetables, fruits, and high-fiber cereals and grains is generally recommended. However, very high\nfiber intake may reduce absorption of certain minerals.\nNutritional Requirements\nGood nutrition aims to achieve and maintain a desirable body composition and high potential for physical\nand mental work. Balancing energy intake with energy expenditure is necessary for a desirable body\nweight. Energy expenditure depends on age, sex, weight (see \nTable 1-4\n), and metabolic and physical\nactivity. If energy intake exceeds expenditure, weight is gained. Taking in about 100 calories/day more\nthan needed results in a weight gain of about 4 to 5 kg in a year. If energy intake is less than expenditure,\nweight is lost.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 1. Nutrition: General Considerations\n55"}


created_at: 2025-06-20 08:54:40
topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
id: 583fd31b-2559-46d9-be68-64ab5ea22126
encoding: FLOAT32
metadata:
{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 3, "chroma:document": "Daily dietary requirements for essential nutrients also depend on age, sex, weight, and metabolic and\nphysical activity. Every 5 yr, the Food and Nutrition Board of the National Academy of Sciences/National\nResearch Council and the US Department of Agriculture (USDA) issues the dietary reference intakes\n(DRIs) for protein, energy, and some vitamins and minerals (see \nTables 1-4\n,\n4-1\n, and \n5-2\n). For vitamins and minerals about which less is known, safe and adequate daily dietary\nintakes are estimated.\nPregnant women (see p. \n2608\n) and infants (see p. \n2703\n) have special nutritional needs.\nThe USDA publishes the Food Guide Pyramid, which specifies the number of recommended daily\nservings of various food groups. The recommendations are individualized based on age, sex, and\nphysical activity (see\nTable 1-5\n). Generally, the recommended intake decreases with aging because physical activity tends to\ndecrease, resulting in less energy expended. The new Food Guide Pyramid emphasizes the following:\n\u2022 Increasing consumption of whole grains\n\u2022 Increasing consumption of vegetables and fruits\n\u2022 Substituting fat-free or low-fat milk products (or equivalents) for whole-fat milk products\n\u2022 Reducing consumption of saturated fats and trans fatty acids\n\u2022 Exercising regularly\nAdequate fluid intake is also important.\nFats should constitute \u2264 30% of total calories, and saturated and trans fatty acids should constitute <\n10%. Excess intake of saturated fats contributes to atherosclerosis. Substituting polyunsaturated fatty\nacids for saturated fats can decrease the risk of atherosclerosis. Routine use of nutritional supplements is\nnot necessary or beneficial; some supplements can be harmful. For example, excess vitamin A can lead to\nhypervitaminosis A, with headaches, osteoporosis, and rash.\nNutrition in Clinical Medicine\nNutritional deficiencies can often worsen health outcomes (whether a disorder is present or not), and\nsome disorders (eg, malabsorption) can cause nutritional deficiencies. Also, many patients (eg, elderly\npatients during acute hospitalization) have unsuspected nutritional deficiencies that require treatment.\nMany medical centers have multi-disciplinary nutrition support teams of physicians, nurses, dietitians, and\npharmacists to help the clinician prevent, diagnose, and treat occult nutritional deficiencies.\nOvernutrition may contribute to chronic disorders, such as cancer, hypertension, obesity, diabetes\nmellitus, and coronary artery disease. Dietary restrictions are necessary in many hereditary metabolic\ndisorders (eg, galactosemia, phenylketonuria).\nEvaluation of Nutritional Status\nIndications for nutritional evaluation include undesirable body weight or body composition, suspicion of\nspecific deficiencies or toxicities\n[\nTable 1-5.\n Recommended Dietary Intake for 40-yr-Olds with Moderate Physical Activity*]\nof essential nutrients, and, in infants and children, insufficient growth or development. Nutritional status\nshould be evaluated routinely as part of the clinical examination for infants and children, the elderly,\npeople taking several drugs, people with psychiatric disorders, and people with systemic disorders that\nlast longer than several days.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 1. Nutrition: General Considerations\n56"}


created_at: 2025-06-20 08:54:40
topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
id: 83f71ac4-04c3-4b7a-916a-48c0f25da92e
encoding: FLOAT32
metadata:
{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 4, "chroma:document": "Evaluating general nutritional status includes history, physical examination, and sometimes tests. If\nundernutrition is suspected, laboratory tests (eg, albumin levels) and skin tests for delayed\nhypersensitivity may be done (see p.\n13\n). Body composition analysis (eg, skinfold measurements, bioelectrical impedance analysis) is used to\nestimate percentage of body fat and to evaluate obesity (see p. \n58\n).\nHistory includes questions about dietary intake, weight change, and risk factors for nutritional deficiencies\nand a focused review of systems (see\nTable 2-1\n on p. \n11\n). A dietitian can obtain a more detailed dietary history. It usually includes a list of foods\neaten within the previous 24 h and a food questionnaire. A food diary may be used to record all foods\neaten. The weighed ad libitum diet, in which the patient weighs and writes down all foods consumed, is\nthe most accurate record.\nA complete physical examination, including measurement of height and weight and distribution of body\nfat, should be done. Body mass index (BMI)\u2014weight(kg)/height(m)\n2\n, which adjusts weight for height (see\nTable 6-2\n on p. \n59\n), is more accurate than height and weight tables. There are standards for growth and\nweight gain in infants, children, and adolescents (see p. \n2756\n).\nDistribution of body fat is important. Disproportionate truncal obesity (ie, waist/hip ratio > 0.8) is\nassociated with cardiovascular and cerebrovascular disorders, hypertension, and diabetes mellitus more\noften than fat located elsewhere. Measuring waist circumference in patients with a BMI of < 35 helps\ndetermine whether they have truncal obesity and helps predict risk of diabetes, hypertension,\nhypercholesterolemia, and cardiovascular disorders. Risk is increased if waist circumference is > 102 cm\n(> 40 in) in men or > 88 cm (> 35 in) in women.\nNutrient-Drug Interactions\nNutrition can affect the body's response to drugs; conversely, drugs can affect the body's nutrition.\nFoods can enhance, delay, or decrease drug absorption. Foods impair absorption of many antibiotics.\nThey can alter metabolism of drugs; eg, high-protein diets can accelerate metabolism of certain drugs by\nstimulating \ncytochrome P-450. Eating grapefruit can inhibit cytochrome P-450 34A, slowing metabolism of\nsome drugs (eg, amiodarone, carbamazepine, cyclosporine, certain Ca channel blockers). Diets that alter\nthe bacterial flora may markedly affect the overall metabolism of certain drugs. Some foods affect the\nbody's response to drugs. For example, tyramine, a component of cheese and a potent vasoconstrictor,\ncan cause hypertensive crisis in some patients who take monoamine oxidase inhibitors and eat cheese.\nNutritional deficiencies can affect drug absorption and metabolism. Severe energy and protein\ndeficiencies reduce enzyme tissue concentrations and may impair the response to drugs by reducing\nabsorption or protein binding and causing liver dysfunction. Changes in the GI tract can impair absorption\nand affect the response to a drug. Deficiency of Ca, Mg, or zinc may impair drug metabolism. Vitamin C\ndeficiency decreases activity of drug-metabolizing enzymes, especially in the elderly.\nMany drugs affect appetite, food absorption, and tissue metabolism (see\nTable 1-6\n). Some drugs (eg, metoclopramide) increase GI motility, decreasing food absorption. Other\ndrugs (eg, opioids, anticholinergics) decrease GI motility. Some drugs are better tolerated if taken with\nfood.\nCertain drugs affect mineral metabolism. For example, diuretics, especially thiazides, and corticosteroids\ncan deplete body K, increasing susceptibility to digoxin-induced cardiac arrhythmias. Repeated use of\nlaxatives may deplete K. Cortisol, desoxycorticosterone, and aldosterone cause marked Na and water\nretention, at least temporarily; retention is much less with prednisone, prednisolone, and some other\ncorticosteroid analogs. Sulfonylureas and lithium can impair the uptake or release of iodine by the thyroid."}


created_at: 2025-06-20 08:54:40
topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
id: c29cff0f-2d66-4871-b3cf-c95e89f7f365
encoding: FLOAT32
metadata:
{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 4, "chroma:document": "corticosteroid analogs. Sulfonylureas and lithium can impair the uptake or release of iodine by the thyroid.\nOral contraceptives can lower blood zinc levels and increase copper levels. Certain antibiotics (eg,\ntetracyclines) reduce iron absorption, as can certain foods (eg, vegetables, tea, bran).\nCertain drugs affect vitamin absorption or metabolism. Ethanol impairs thiamin utilization, and isoniazid\ninterferes with niacin and pyridoxine metabolism. Ethanol and oral contraceptives inhibit folate (folic acid)\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 1. Nutrition: General Considerations\n57"}


created_at: 2025-06-20 08:54:40
topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
id: 80c5ce06-d8ab-42cd-a487-0f1d1013263c
encoding: FLOAT32
metadata:
{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 5, "chroma:document": "absorption. Most patients receiving phenytoin, phenobarbital, primidone, or phenothiazines develop folate\ndeficiency, probably because hepatic microsomal drug-metabolizing enzymes are affected. Folate\nsupplements may\n[\nTable 1-6.\n Effects of Some Drugs on Nutrition]\nmake phenytoin less effective. Anticonvulsants can cause vitamin D deficiency. Malabsorption of vitamin\nB\n12\n can occur with use of aminosalicylic acid, slow-release K iodide, colchicine, trifluoperazine, ethanol,\nand oral contraceptives. Oral contraceptives with a high progestin dose can cause depression, probably\nbecause of metabolically induced tryptophan deficiency.\nFood Additives and Contaminants\nAdditives:\n Chemicals are often combined with foods to facilitate their processing and preservation or to\nenhance their desirability. Only amounts of additives shown to be safe by laboratory tests are permitted in\ncommercially prepared foods.\nWeighing the benefits of additives (eg, reduced waste, increased variety of available foods, protection\nagainst food-borne illness) against the risks is often complex. For example, nitrite, which is used in cured\nmeats, inhibits the growth of \nClostridium botulinum\n and improves flavor. However, nitrite converts to\nnitrosamines, which are carcinogens in animals. On the other hand, the amount of nitrite added to cured\nmeat is small compared with the amount from naturally occurring food nitrates converted to nitrite by the\nsalivary glands. Dietary vitamin C can reduce nitrite formation in the GI tract. Rarely, some additives (eg,\nsulfites) cause food hypersensitivity (allergy) reactions. Most of these reactions are caused by ordinary\nfoods (see p. \n1118\n).\nContaminants:\n Sometimes limited amounts of contaminants are allowed in foods because the\ncontaminants cannot be completely eliminated without damaging the foods. Common contaminants are\npesticides, heavy metals (lead, cadmium, mercury), nitrates (in green leafy vegetables), aflatoxins (in nuts\nand milk), growth-promoting hormones (in dairy products and meat), animal hairs and feces, and insect\nparts.\nFDA-estimated safe levels are levels that have not caused illness or adverse effects in people. However,\ndemonstrating a causal relationship between extremely low level exposures and adverse effects is\ndifficult; long-term adverse effects, although unlikely, are still possible. Safe levels are often determined\nby consensus rather than by hard evidence.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 1. Nutrition: General Considerations\n58"}


created_at: 2025-06-20 08:54:40
topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
id: 0de11a00-a2bd-43f1-9390-2a40a9236028
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 6, "chroma:document": "Chapter 2. Undernutrition\nIntroduction\nUndernutrition is a form of malnutrition. (Malnutrition also includes overnutrition\u2014see \nCh. 6\n).\nUndernutrition can result from inadequate ingestion of nutrients, malabsorption, impaired\nmetabolism, loss of nutrients due to diarrhea, or increased nutritional requirements (as occurs\nin cancer or infection). Undernutrition progresses in stages; each stage usually takes\nconsiderable time to develop. First, nutrient levels in blood and tissues change, followed by\nintracellular changes in biochemical functions and structure. Ultimately, symptoms and signs\nappear.\nRisk Factors\nUndernutrition is associated with many disorders and circumstances, including poverty and social\ndeprivation. Risk is also greater at certain times (ie, during infancy, early childhood, adolescence,\npregnancy, breastfeeding, and old age).\nInfancy and childhood:\n Infants and children are particularly susceptible to undernutrition because of\ntheir high demand for energy and essential nutrients. Because vitamin K does not readily cross the\nplacenta, neonates may be deficient, so all are given a single injection of vitamin K within 1 h of birth to\nprevent hemorrhagic disease of the newborn, a life-threatening disorder (see pp. \n46\n and\n2783\n). Infants fed only breast milk, which is typically low in vitamin D, are given supplemental vitamin D;\nthey can develop vitamin B\n12\n deficiency if the mother is a vegan. Inadequately fed infants and children\nare at risk of protein-energy undernutrition (PEU\u2014previously called protein-energy malnutrition) and\ndeficiencies of iron, folate (folic acid), vitamins A and C, copper, and zinc. During adolescence, nutritional\nrequirements increase because the growth rate accelerates. Anorexia nervosa (see p. \n1535\n) may affect\nadolescent girls in particular.\nPregnancy and breastfeeding:\n Requirements for nutrients increase during pregnancy and\nbreastfeeding. Aberrations of diet, including pica (consumption of nonnutritive substances, such as clay\nand charcoal), may occur during \npregnancy. Anemia due to iron deficiency is common, as is anemia due\nto folate deficiency, especially among women who have taken oral contraceptives. Vitamin D deficiency is\ncommon during late pregnancy, predisposing the child to decreased bone mass.\nOld age:\n Aging\u2014even when disease or dietary deficiency is absent\u2014leads to sarcopenia (progressive\nloss of lean body mass), starting after age 40 and eventually amounting to a muscle loss of about 10 kg\n(22 lb) in men and 5 kg (11 lb) in women. Undernutrition contributes to sarcopenia, and sarcopenia\naccounts for many of the complications of undernutrition (eg, decreased nitrogen balance, increased\nsusceptibility to infections). Causes of sarcopenia include the following:\n\u2022 Decreased physical activity\n\u2022 Decreased food intake\n\u2022 Increased levels of cytokines (particularly interleukin-6)\n\u2022 Decreased levels of growth hormone and mechano growth factor (insulin-like growth factor-3)\n\u2022 In men, decreasing androgen levels\nAging decreases basal metabolic rate (due mainly to decreased fat-free mass), total body weight, height,\nand skeletal mass; aging increases mean body fat (as a percentage of body weight) to about 30% (from\n20%) in men and to 40% (from 27%) in women.\nFrom age 20 to 80, food intake decreases, especially in men. Anorexia due to aging itself has many\ncauses, including reduced adaptive relaxation of the stomach's fundus, increased release and activity of\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2. Undernutrition\n59"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 7, "chroma:document": "cholecystokinin (which produces satiation), and increased leptin (an anorectic hormone produced by fat\ncells). Diminished taste and smell can decrease eating pleasure but usually decrease food intake only\nslightly. Anorexia may have other causes (eg, loneliness, inability to shop or prepare meals, dementia,\nsome chronic disorders, use of certain drugs). Depression is a common cause. Occasionally, anorexia\nnervosa (sometimes called anorexia tardive in the elderly), paranoia, or mania interferes with eating.\nDental problems limit the ability to chew and subsequently to digest foods. Swallowing difficulties (eg, due\nto strokes, other neurologic disorders, esophageal candidiasis, or xerostomia) are common. Poverty or\nfunctional impairment limits access to nutrients.\nThe institutionalized elderly are at particular risk of PEU. They are often confused and may be unable to\nexpress hunger or preferences for foods. They may be physically unable to feed themselves. Chewing or\nswallowing may be very slow, making it tedious for another person to feed them enough food.\nIn the elderly, particularly the institutionalized elderly, inadequate intake and often decreased absorption\nor synthesis of vitamin D, increased demand for vitamin D, and inadequate exposure to sunshine\ncontribute to osteomalacia (see p. \n41\n).\nDisorders and medical procedures:\n Diabetes, some chronic disorders that affect the GI tract, intestinal\nresection, and certain other GI surgical procedures tend to impair absorption of fat-soluble vitamins,\nvitamin B\n12\n, Ca, and iron. Gluten enteropathy, pancreatic insufficiency, or other disorders can result in\nmalabsorption. Decreased absorption possibly contributes to iron deficiency and osteoporosis. Liver\ndisorders impair storage of vitamins A and B\n12\n and interfere with metabolism of protein and energy\nsources. Renal insufficiency predisposes to protein, iron, and vitamin D deficiencies. Anorexia causes\nsome patients with cancer or depression and many with AIDS to consume inadequate amounts of food.\nInfections, trauma, hyperthyroidism, extensive burns, and prolonged fever increase metabolic demands.\nAny condition that increases cytokines may be accompanied by muscle loss, lipolysis, low albumin levels,\nand anorexia.\nVegetarian diets:\n Iron deficiency can occur in ovo-lacto vegetarians (although such a diet can be\ncompatible with good health). Vegans may develop vitamin B\n12\n deficiency unless they consume yeast\nextracts or Asian-style fermented foods. Their intake of Ca, iron, and zinc also tends to be low. A fruit-only\ndiet is not recommended because it is deficient in protein, Na, and many micronutrients.\nFad diets:\n Some fad diets result in vitamin, mineral, and protein deficiencies; cardiac, renal, and\nmetabolic disorders; and sometimes death. Very low calorie diets (< 400 kcal/day) cannot sustain health\nfor long.\nDrugs and nutritional supplements:\n Many drugs (eg, appetite suppressants, digoxin) decrease\nappetite; others impair nutrient absorption or metabolism. Some drugs (eg, stimulants) have catabolic\neffects. Certain drugs can impair absorption of many nutrients; eg, anticonvulsants can impair absorption\nof vitamins.\nAlcohol or drug dependency:\n Patients with alcohol or drug dependency may neglect their nutritional\nneeds. Absorption and metabolism of nutrients may also be impaired. IV drug addicts typically become\nundernourished, as do\n[\nTable 2-1.\n Symptoms and Signs of Nutritional Deficiency]\nalcoholics who consume \u2265 1 quart of hard liquor/day. Alcoholism can cause deficiencies of Mg, zinc, and\ncertain vitamins, including thiamin.\nSymptoms and Signs\nSymptoms vary depending on the cause and type of undernutrition (see p. \n15\n and \nChs. 4\n and \n5\n).\nEvaluation\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2. Undernutrition\n60"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 8, "chroma:document": "Diagnosis is based on results of medical and diet histories, physical examination, body composition\nanalysis (see p. \n58\n), and selected laboratory tests.\nHistory:\n History should include questions about dietary intake (see\nFig. 2-1\n), recent changes in weight, and risk factors for undernutrition, including drug and alcohol use.\nUnintentional loss of \u2265 10% of usual body weight during a 3-mo period indicates a high probability of\nundernutrition. Social history should include questions about whether money is available for food and\nwhether the patient can shop and cook.\nReview of systems should focus on symptoms of nutritional deficiencies (see \nTable 2-1\n). For example,\nimpaired night vision may indicate vitamin A deficiency.\nPhysical examination:\n Physical examination should include measurement of height and weight,\ninspection of body fat distribution, and anthropometric measurements of lean body mass. Body mass\nindex (BMI = weight(kg)/height(m)\n2\n) adjusts weight for height (see\nTable 6-2\n on p. \n59\n). If weight is < 80% of what is predicted for the patient's height or if BMI is \u2264 18,\nundernutrition should be suspected. Although these findings are useful in diagnosing undernutrition and\nare acceptably sensitive, they lack specificity.\n[\nFig. 2-1.\n Mini nutritional assessment.]\nThe mid upper arm muscle area estimates lean body mass. This area is derived from the triceps skinfold\nthickness (TSF) and mid upper arm circumference. Both are measured at the same site, with the patient's\nright arm in a relaxed position. The average mid upper arm circumference is about 32 \u00b1 5 cm for men and\n28 \u00b1 6 cm for women. The formula for calculating the mid upper arm muscle area in cm\n2\n is as follows:\nThis formula corrects the upper arm area for fat and bone. Average values for the mid upper arm muscle\narea are 54 \u00b1 11 cm\n2\n for men and 30 \u00b1 7 cm\n2\n for women. A value < 75% of this standard (depending on\nage) indicates depletion of lean body mass (see\nTable 2-2\n). This measurement may be affected by physical activity, genetic factors, and age-related\nmuscle loss.\nPhysical examination should focus on signs of specific nutritional deficiencies. Signs of PEU (eg, edema,\nmuscle wasting, skin changes) should be sought. Examination should also focus on signs of conditions\nthat could predispose to nutritional deficiencies, such as dental problems. Mental status should be\nassessed, because depression and cognitive impairment can lead to weight loss.\nThe widely used Subjective Global Assessment (SGA) uses information from the patient history (eg,\nweight loss, change in intake, GI symptoms), physical examination findings (eg, loss of muscle and\nsubcutaneous fat, edema, ascites), and the clinician's judgment of the patient's nutritional status. The\nMini Nutritional Assessment (MNA) has been validated and is widely used, especially for elderly patients\n(see \nFig. 2-1\n). The Simplified Nutrition Assessment Questionnaire (SNAQ), a simple, validated method of\npredicting future weight loss, may be used (see\nFig. 2-2\n).\nTesting:\n The extent of laboratory testing needed is unclear and may depend on the patient's\ncircumstances. If the cause is obvious and correctable (eg, a wilderness survival situation), testing is\nprobably of little benefit. Other patients may require more detailed evaluation.\nSerum albumin measurement is the laboratory test most often used. Decreases in albumin and other\nproteins (eg, prealbumin [transthyretin], transferrin, retinol-binding protein) may indicate protein deficiency\nor PEU. As undernutrition progresses, albumin decreases slowly; prealbumin, transferrin, and retinol-\nbinding protein decrease rapidly. Albumin measurement is inexpensive and predicts morbidity and\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2. Undernutrition\n61"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 9, "chroma:document": "mortality better than measurement of the other proteins. However, the correlation of albumin with\nmorbidity and mortality may be related to nonnutritional as well as nutritional factors. Inflammation\nproduces cytokines that cause albumin and other nutritional protein markers to extravasate, decreasing\nserum levels. Because prealbumin, transferrin, and retinol-binding protein decrease more rapidly during\nstarvation than does albumin, their measurements are sometimes used to diagnose or assess the severity\nof acute starvation. However, whether they are more sensitive or specific than albumin is unclear.\nTotal lymphocyte count, which often decreases as undernutrition progresses, may be determined.\nUndernutrition causes a marked decline in CD4+ T lymphocytes, so this count may not be useful in\npatients who have AIDS.\nSkin tests using antigens can detect impaired cell-mediated immunity in PEU and in some other disorders\nof undernutrition (see p.\n1098\n).\nOther laboratory tests, such as measuring vitamin and mineral levels, are used selectively to diagnose\nspecific deficiencies.\n[\nTable 2-2.\n Mid Upper Arm Muscle Area in Adults]\n[\nFigure 2-2.\n Simplified Nutrition Assessment Questionnaire (SNAQ).]\nProtein-Energy Undernutrition\nProtein-energy undernutrition (PEU), previously called protein-energy malnutrition, is an energy\ndeficit due to chronic deficiency of all macronutrients. It commonly includes deficiencies of\nmany micronutrients. PEU can be sudden and total (starvation) or gradual. Severity ranges from\nsubclinical deficiencies to obvious wasting (with edema, hair loss, and skin atrophy) to\nstarvation. Multiple organ systems are often impaired. Diagnosis usually involves laboratory\ntesting, including serum albumin. Treatment consists of correcting fluid and electrolyte deficits\nwith IV solutions, then gradually replenishing nutrients, orally if possible.\nIn developed countries, PEU is common among the institutionalized elderly (although often not suspected)\nand among patients with disorders that decrease appetite or impair nutrient digestion, absorption, or\nmetabolism. In developing countries, PEU affects children who do not consume enough calories or\nprotein.\nClassification and Etiology\nPEU is graded as mild, moderate, or severe. Grade is determined by calculating weight as a percentage\nof expected weight for length or height using international standards (normal, 90 to 110%; mild PEU, 85 to\n90%; moderate, 75 to 85%; severe, <75%).\nPEU may be primary or secondary. Primary PEU is caused by inadequate nutrient intake. \nSecondary PEU\nresults from disorders or drugs that interfere with nutrient use.\nPrimary PEU:\n Worldwide, primary PEU occurs mostly in children and the elderly who lack access to\nnutrients, although a common cause in the elderly is depression. PEU can also result from fasting or\nanorexia nervosa. Child or elder abuse may be a cause.\nIn children, chronic primary PEU has 2 common forms: marasmus and kwashiorkor. The form depends on\nthe balance of nonprotein and protein sources of energy. Starvation is an acute severe form of primary\nPEU.\nMarasmus (also called the dry form of PEU) causes weight loss and depletion of fat and muscle. In\ndeveloping countries, marasmus is the most common form of PEU in children.\nKwashiorkor (also called the wet, swollen, or edematous form) is associated with premature abandonment\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2. Undernutrition\n62"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 10, "chroma:document": "of breastfeeding, which typically occurs when a younger sibling is born, displacing the older child from the\nbreast. So children with kwashiorkor tend to be older than those with marasmus. Kwashiorkor may also\nresult from an acute illness, often gastroenteritis or another infection (probably secondary to cytokine\nrelease), in a child who already has PEU. A diet that is more deficient in protein than energy may be more\nlikely to cause kwashiorkor than marasmus. Less common than marasmus, kwashiorkor tends to be\nconfined to specific parts of the world, such as rural Africa, the Caribbean, and the Pacific islands. In\nthese areas, staple foods (eg, yams, cassavas, sweet potatoes, green bananas) are low in protein and\nhigh in carbohydrates. In kwashiorkor, cell membranes leak, causing extravasation of intravascular fluid\nand protein, resulting in peripheral edema.\nStarvation is a complete lack of nutrients. It occasionally occurs when food is available (as in fasting or\nanorexia nervosa) but usually occurs because food is unavailable (eg, during famine or wilderness\nexposure).\nSecondary PEU:\n This type most commonly results from the following:\n\u2022 Disorders that affect GI function: These disorders can interfere with digestion (eg, pancreatic\ninsufficiency), absorption (eg, enteritis, enteropathy), or lymphatic transport of nutrients (eg,\nretroperitoneal fibrosis, Milroy's disease).\n\u2022 Wasting disorders: In wasting disorders (eg, AIDS, cancer) and renal failure, catabolism causes cytokine\nexcess, resulting in undernutrition via anorexia and cachexia (wasting of muscle and fat). End-stage\nheart failure can cause cardiac cachexia, a severe form of undernutrition; mortality rate is particularly\nhigh. Factors contributing to cardiac cachexia may include passive hepatic congestion (causing\nanorexia), edema of the intestinal tract (impairing absorption), and, in advanced disease, increased O\n2\nrequirement due to anaerobic metabolism. Wasting disorders can decrease appetite or impair\nmetabolism of nutrients.\n\u2022 Conditions that increase metabolic demands: These conditions include infections, hyperthyroidism,\npheochromocytoma, other endocrine disorders, burns, trauma, surgery, and other critical illnesses.\nPathophysiology\nThe initial metabolic response is decreased metabolic rate. To supply energy, the body first breaks down\nadipose tissue. However, later when these tissues are depleted, the body may use protein for energy,\nresulting in a negative nitrogen balance. Visceral organs and muscle are broken down and decrease in\nweight. Loss of organ weight is greatest in the liver and intestine, intermediate in the heart and kidneys,\nand least in the nervous system.\nSymptoms and Signs\nSymptoms of moderate PEU can be constitutional or involve specific organ systems. Apathy and irritability\nare common. The patient is weak, and work capacity decreases. Cognition and sometimes\nconsciousness are impaired. Temporary lactose deficiency and achlorhydria develop. Diarrhea is common\nand can be aggravated by deficiency of intestinal disaccharidases, especially lactase (see p. \n157\n).\nGonadal tissues atrophy. PEU can cause amenorrhea in women and loss of libido in men and women.\nWasting of fat and muscle is common in all forms of PEU. In adult volunteers who fasted for 30 to 40\ndays, weight loss was marked (25% of initial weight). If starvation is more prolonged, weight loss may\nreach 50% in adults and possibly more in children.\nIn adults, cachexia is most obvious in areas where prominent fat depots normally exist. Muscles shrink\nand bones protrude. The skin becomes thin, dry, inelastic, pale, and cold. The hair is dry and falls out\neasily, becoming sparse. Wound healing is impaired. In elderly patients, risk of hip fractures and pressure\n(decubitus) ulcers increases.\nWith acute or chronic severe PEU, heart size and cardiac output decrease; pulse slows\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2. Undernutrition\n63"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 11, "chroma:document": "[\nTable 2-3.\n Values Commonly Used to Grade the Severity of Protein-Energy Undernutrition]\nand BP falls. Respiratory rate and vital capacity decrease. Body temperature falls, sometimes contributing\nto death. Edema, anemia, jaundice, and petechiae can develop. Liver, kidney, or heart failure may occur.\nCell-mediated immunity is impaired, increasing susceptibility to infections. Bacterial infections (eg,\npneumonia, gastroenteritis, otitis media, UTIs, sepsis) are common in both forms of PEU. Infections result\nin release of cytokines, which cause anorexia, worsen muscle wasting, and cause a marked decrease in\nserum albumin levels.\nMarasmus in infants causes hunger, weight loss, growth retardation, and wasting of subcutaneous fat\nand muscle. Ribs and facial bones appear prominent. Loose, thin skin hangs in folds.\nKwashiorkor is characterized by peripheral and periorbital edema. The abdomen protrudes because\nabdominal muscles are weakened, the intestine is distended, the liver enlarges, and ascites is present.\nThe skin is dry, thin, and wrinkled; it can become hyperpigmented and fissured and later hypopigmented,\nfriable, and atrophic. Skin in different areas of the body may be affected at different times. The hair can\nbecome thin, reddish brown, or gray. Scalp hair falls out easily, eventually becoming sparse, but eyelash\nhair may grow excessively. Alternating episodes of undernutrition and adequate nutrition may cause the\nhair to have a dramatic \"striped flag\" appearance. Affected children may be apathetic but become irritable\nwhen held.\nTotal starvation is fatal in 8 to 12 wk. Thus, certain symptoms of PEU do not have time to develop.\nDiagnosis\n\u2022 Diagnosis usually based on history\n\u2022 To determine severity: BMI, serum albumin, total lymphocyte count, CD4+ count, serum transferrin\n\u2022 To diagnose complications and consequences: CBC, electrolytes, BUN, glucose, Ca, Mg, phosphate\nDiagnosis can be based on history when dietary intake is markedly inadequate. The cause of inadequate\nintake, particularly in children, needs to be identified. In children and adolescents, child abuse and\nanorexia nervosa should be considered.\nPhysical examination findings can usually confirm the diagnosis. Laboratory tests are required if dietary\nhistory does not clearly indicate inadequate caloric intake. Measurement of serum albumin, total\nlymphocyte count, CD4+ T lymphocytes, transferrin, and response to skin antigens may help determine\nthe severity of PEU (see \nTable 2-3\n) or confirm the diagnosis in borderline cases. Many other test results\nmay be abnormal: eg, decreased levels of hormones, vitamins, lipids, cholesterol, prealbumin, insulin\ngrowth factor-1, fibronectin, and retinol-binding protein. Urinary creatine and methylhistidine levels can be\nused to gauge the degree of muscle wasting. Because protein catabolism slows, urinary urea level also\ndecreases. These findings rarely affect treatment.\nLaboratory tests are required to identify causes of suspected secondary PEU. C-reactive protein or\nsoluble interleukin-2 receptor should be measured when the cause of undernutrition \nis unclear; these\nmeasurements can help determine whether there is cytokine excess. Thyroid function tests may also be\ndone.\nOther laboratory tests can detect associated abnormalities that may require treatment. Serum\nelectrolytes, BUN, glucose, and possibly levels of Ca, Mg, and phosphate should be measured. Levels of\nserum glucose, electrolytes (especially K, occasionally Na), phosphate, Ca, and Mg are usually low. BUN\nis often low unless renal failure is present. Metabolic acidosis may be present. CBC is usually obtained;\nnormocytic anemia (usually due to protein deficiency) or microcytic anemia (due to simultaneous iron\ndeficiency) is usually present.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2. Undernutrition\n64"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 12, "chroma:document": "Stool cultures should be obtained and checked for ova and parasites if diarrhea is severe or does not\nresolve with treatment. Sometimes urinalysis, urine culture, blood cultures, tuberculin testing, and a chest\nx-ray are used to diagnose occult infections because people with PEU may have a muted response to\ninfections.\nPrognosis\nChildren:\n In children, mortality varies from 5 to 40%. Mortality rates are lower in children with mild PEU\nand those given intensive care. Death in the first days of treatment is usually due to electrolyte deficits,\nsepsis, hypothermia, or heart failure. Impaired consciousness, jaundice, petechiae, hyponatremia, and\npersistent diarrhea are ominous signs. Resolution of apathy, edema, and anorexia is a favorable sign.\nRecovery is more rapid in kwashiorkor than in marasmus.\nLong-term effects of PEU in children are not fully documented. Some children develop chronic\nmalabsorption and pancreatic insufficiency. In very young children, mild intellectual disability may develop\nand persist until at least school age. Permanent cognitive impairment may occur, depending on the\nduration, severity, and age at onset of PEU.\nAdults:\n In adults, PEU can result in morbidity and mortality (eg, progressive weight loss increases\nmortality rate for elderly patients in nursing homes). In elderly patients, PEU increases the risk of\nmorbidity and mortality due to surgery, infections, or other disorders. Except when organ failure occurs,\ntreatment is uniformly successful.\nTreatment\n\u2022 Usually, oral feeding\n\u2022 Possibly avoidance of lactose (eg, if persistent diarrhea suggests lactose intolerance)\n\u2022 Supportive care (eg, environmental changes, assistance with feeding, orexigenic drugs)\n\u2022 For children, feeding delayed 24 to 48 h\nWorldwide, the most important preventive strategy is to reduce poverty and improve nutritional education\nand public health measures.\nMild or moderate PEU, including brief starvation, can be treated by providing a balanced diet, preferably\norally. Liquid oral food supplements (usually lactose-free) can be used when solid food cannot be\nadequately ingested. Diarrhea often complicates oral feeding because starvation makes the GI tract more\nlikely to move bacteria into Peyer's patches, facilitating infectious diarrhea. If diarrhea persists\n(suggesting lactose intolerance), yogurt-based rather than milk-based formulas are given because people\nwith lactose intolerance can tolerate yogurt. Patients should also be given a multivitamin supplement.\nSevere PEU or prolonged starvation requires treatment in a hospital with a controlled diet. The first\npriority is to correct fluid and electrolyte abnormalities (see \nCh. 97\n) and treat infections. Next is to supply\nmacronutrients orally or, if necessary (eg, when swallowing is difficult), through a feeding tube, a\nnasogastric tube (usually), or a gastrostomy tube. Parenteral nutrition is indicated if malabsorption is\nsevere (see p. \n23\n).\nOther treatments may be needed to correct specific deficiencies, which may become evident as weight\nincreases. To avoid deficiencies, patients should take micronutrients at about twice the recommended\ndaily allowance (RDA) until recovery is complete.\nChildren:\n Underlying disorders should be treated. For children with diarrhea, feeding may be delayed 24\nto 48 h to avoid making the diarrhea worse; during this interval, children require oral or IV rehydration.\nFeedings are given often (6 to 12 times/day) but, to avoid overwhelming the limited intestinal absorptive\ncapacity, are limited to small amounts (< 100 mL). During the first week, milk-based formulas with\nsupplements added are usually given in progressively increasing amounts; after a week, the full amounts\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2. Undernutrition\n65"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 13, "chroma:document": "of 175 kcal/kg and 4 g of protein/kg can be given. Twice the RDA of micronutrients should be given,\nusing commercial multivitamin supplements. After 4 wk, the formula can be replaced with whole milk plus\ncod liver oil and solid foods, including eggs, fruit, meats, and yeast.\nEnergy distribution among macronutrients should be about 16% protein, 50% fat, and 34% carbohydrate.\nAn example is a combination of powdered cow's skimmed milk (110 g), sucrose (100 g), vegetable oil (70\ng), and water (900 mL). Many other formulas (eg, whole [full-fat] fresh milk plus corn oil and maltodextrin)\ncan be used. Milk powders used in formulas are diluted with water.\nUsually, supplements should be added to formulas:\n\u2022 Mg 0.4 mEq/kg/day IM is given for 7 days.\n\u2022 B-complex vitamins at twice the RDA are given parenterally for the first 3 days, usually with vitamin A,\nphosphorus, zinc, manganese, copper, iodine, fluoride, molybdenum, and selenium.\n\u2022 Because absorption of oral iron is poor in children with PEU, oral or IM iron supplementation may be\nnecessary.\nParents are taught about nutritional requirements.\nAdults:\n Underlying disorders should be treated. For example, if AIDS or cancer results in excess cytokine\nproduction, megestrol acetate or medroxyprogesterone may improve food intake. However, because\nthese drugs dramatically decrease testosterone in men (possibly causing muscle loss), testosterone\nshould be replaced. Because these drugs can cause adrenal insufficiency, they should be used only\nshort-term (< 3 mo).\nIn patients with functional limitations, home delivery of meals and feeding assistance are key.\nAn orexigenic drug, such as the cannabis extract dronabinol, should be given to patients with anorexia\nwhen no cause is obvious or to patients at the end of life when anorexia impairs quality of life. An\nanabolic steroid (eg, enanthate, nandrolone, testosterone) or growth hormone can benefit patients with\ncachexia due to renal failure and possibly elderly patients (eg, by increasing lean body mass or possibly\nby improving function).\nCorrection of PEU in adults generally resembles that in children; feedings are often limited to small\namounts. However, for most adults, feeding does not need to be delayed. A commercial formula for oral\nfeeding can be used. Daily nutrient supply should be given at a rate of 60 kcal/kg and 1.2 to 2 g of\nprotein/kg. If liquid oral supplements are used with solid food, they should be given at least 1 h before\nmeals so that the amount of food eaten at the meal is not reduced.\nTreatment of institutionalized elderly patients with PEU requires multiple interventions:\n\u2022 Environmental measures (eg, making the dining area more attractive)\n\u2022 Feeding assistance\n\u2022 Changes in diet (eg, use of food enhancers and caloric supplements between meals)\n\u2022 Treatment of depression and other underlying disorders\n\u2022 Use of orexigenics, anabolic steroids, or both\nThe long-term use of gastrostomy tube feeding is essential for patients with severe dysphagia; its use in\npatients with dementia is controversial. Increasing evidence supports the avoidance of unpalatable\ntherapeutic diets (eg, low salt, diabetic, low cholesterol) in institutionalized patients because these diets\ndecrease food intake and may cause severe PEU.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2. Undernutrition\n66"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 14, "chroma:document": "Complications of treatment:\n Treatment of PEU can cause complications (refeeding syndrome),\nincluding fluid overload, electrolyte deficits, hyperglycemia, cardiac arrhythmias, and diarrhea. Diarrhea is\nusually mild and resolves; however, diarrhea in patients with severe PEU occasionally causes severe\ndehydration or death. Causes of diarrhea (eg, sorbitol used in elixir tube feedings, \nClostridium difficile\n if\nthe patient has received an antibiotic) may be correctable. Osmotic diarrhea due to excess calories is rare\nin adults and should be considered only when other causes have been excluded.\nBecause PEU can impair cardiac and renal function, hydration can cause intravascular volume overload.\nTreatment decreases extra-cellular K and Mg. Depletion of K or Mg may cause arrhythmias.\nCarbohydrate metabolism that occurs during treatment stimulates insulin release, which drives phosphate\ninto cells. Hypophosphatemia can cause muscle weakness, paresthesias, seizures, coma, and\narrhythmias. Because phosphate levels can change rapidly during parenteral feeding, levels should be\nmeasured regularly.\nDuring treatment, endogenous insulin may become ineffective, leading to hyperglycemia. Dehydration\nand hyperosmolarity can result. Fatal ventricular arrhythmias can develop, possibly caused by a\nprolonged QT interval.\nCarnitine Deficiency\nCarnitine deficiency results from inadequate intake of or inability to metabolize the amino acid\ncarnitine. It can cause a heterogeneous group of disorders. Muscle metabolism is impaired,\ncausing myopathy, hypoglycemia, or cardiomyopathy. Infants typically present with\nhypoglycemic, hypoketotic encephalopathy. Most often, treatment consists of dietary L-\ncarnitine.\nThe amino acid carnitine is required for the transport of long-chain fatty acyl coenzyme A (CoA) esters\ninto myocyte mitochondria, where they are oxidized for energy. Carnitine is obtained from foods,\nparticularly animal-based foods, and via endogenous synthesis.\nCauses of carnitine deficiency include the following:\n\u2022 Inadequate intake (eg, due to fad diets, lack of access, or long-term TPN)\n\u2022 Inability to metabolize carnitine due to enzyme deficiencies (eg, carnitine palmitoyltransferase deficiency,\nmethylmalonicaciduria, propionicacidemia, isovalericacidemia)\n\u2022 Decreased endogenous synthesis of carnitine due to a severe liver disorder\n\u2022 Excess loss of carnitine due to diarrhea, diuresis, or hemodialysis\n\u2022 A hereditary disorder in which carnitine leaks from renal tubules\n\u2022 Increased requirements for carnitine when ketosis is present or demand for fat oxidation is high (eg,\nduring a critical illness such as sepsis or major burns; after major surgery of the GI tract)\n\u2022 Decreased muscle carnitine levels due to mitochondrial impairment (eg, due to use of zidovudine)\n\u2022 Use of valproate\nThe deficiency may be generalized (systemic) or may affect mainly muscle (myopathic).\nSymptoms and Signs\nSymptoms and the age at which symptoms appear depend on the cause. Carnitine deficiency may cause\nmuscle necrosis, myoglobinuria, lipid-storage myopathy, hypoglycemia, fatty liver, and hyperammonemia\nwith muscle aches, fatigue, confusion, and cardiomyopathy.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2. Undernutrition\n67"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 15, "chroma:document": "Diagnosis\nIn neonates, carnitine palmitoyltransferase deficiency is diagnosed using mass spectrometry to screen\nblood. Prenatal diagnosis may be possible using amniotic villous cells. In adults, the definitive diagnosis is\nbased on acylcarnitine levels in serum, urine, and tissues (muscle and liver for systemic deficiency;\nmuscle only for myopathic deficiency).\nTreatment\n\u2022 Avoidance of fasting and strenuous exercise\n\u2022 Dietary interventions, based on cause\nCarnitine deficiency due to inadequate dietary intake, increased requirements, excess losses, decreased\nsynthesis, or (sometimes) enzyme deficiencies can be treated by giving L-carnitine 25 mg/kg po q 6 h.\nAll patients must avoid fasting and strenuous exercise. Consuming uncooked cornstarch at bedtime\nprevents early morning hypoglycemia. Some patients require supplementation with medium-chain\ntriglycerides and essential fatty acids (eg, linoleic acid, linolenic acid). Patients with a fatty acid oxidation\ndisorder require a high-carbohydrate, low-fat diet.\nEssential Fatty Acid Deficiency\nEssential fatty acid (EFA) deficiency is rare, occurring most often in infants fed diets deficient in\nEFAs. Signs include scaly dermatitis, alopecia, thrombocytopenia, and, in children, growth\nretardation. Diagnosis is clinical. Dietary replenishment of EFAs reverses the deficiency.\nThe EFAs linoleic and linolenic acid are substrates for the endogenous synthesis of other fatty acids that\nare needed for many physiologic processes, including maintaining the integrity of skin and cell\nmembranes and synthesizing prostaglandins and leukotrienes. For example, eicosapentaenoic acid and\ndocosahexaenoic acid, synthesized from EFAs, are important components of the brain and retina.\nFor EFA deficiency to develop, dietary intake must be very low. Even small amounts of EFAs can prevent\nEFA deficiency. Cow's milk has only about 25% of the linoleic acid in human milk, but when ingested in\nnormal amounts, it has enough linoleic acid to prevent EFA deficiency. Total fat intake of people in many\ndeveloping countries may be very low, but the fat is often vegetable based, with large amounts of linoleic\nacid and enough linolenic acid to prevent EFA deficiency.\nBabies fed a formula low in linoleic acid, such as a skim-milk formula, can develop EFA deficiency. EFA\ndeficiency used to result from long-term TPN if fat was not included. But now, most TPN solutions include\nfat emulsions to prevent EFA deficiency. In patients with fat malabsorption or increased metabolic needs\n(eg, because of surgery, multiple trauma, or burns), laboratory evidence of EFA deficiency may be\npresent without clinical signs.\nDermatitis due to EFA deficiency is generalized and scaly; in infants, it can resemble congenital\nichthyosis. The dermatitis increases water loss from the skin.\nDiagnosis is usually clinical; however, laboratory assays are now available in large research centers.\nTreatment consists of dietary EFAs, reversing the deficiency.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 2. Undernutrition\n68"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 16, "chroma:document": "Chapter 3. Nutritional Support\nIntroduction\nMany undernourished patients need nutritional support, which aims to increase lean body mass. Oral\nfeeding can be difficult for some patients with anorexia or with eating or absorption problems. Behavioral\nmeasures that sometimes enhance oral intake include the following:\n\u2022 Encouraging patients to eat\n\u2022 Heating or seasoning foods\n\u2022 Providing favorite or strongly flavored foods\n\u2022 Encouraging patients to eat small portions\n\u2022 Scheduling around meals\n\u2022 Assisting patients with feeding\nIf behavioral measures are ineffective, nutritional support\u2014oral, enteral tube, or parenteral nutrition\u2014is\nindicated, except sometimes for dying or severely demented patients (see p. \n25\n).\nPredicting Nutritional Requirements\nNutritional requirements are predicted so that interventions can be planned. Requirements can be\nestimated by formulas or measured by indirect calorimetry. Indirect calorimetry requires use of a metabolic\ncart (a closed rebreathing system that determines energy expenditure based on total CO\n2\n production),\nwhich requires special expertise and is not always available. Thus, total energy expenditure (TEE) and\nprotein requirements usually are estimated.\nEnergy expenditure:\n TEE varies based on the patient's weight, activity level, and degree of metabolic\nstress (metabolic demands); TEE ranges from 25 kcal/kg/day for people who are sedentary and not under\nstress to about 40 kcal/kg/day for people who are critically ill. TEE equals the sum of\n\u2022 Resting metabolic rate (RMR, or resting energy expenditure rate), which is normally about 70% of TEE\n\u2022 Energy dissipated by metabolism of food (10% of TEE)\n\u2022 Energy expended during physical activity (20% of TEE)\nUndernutrition can decrease RMR up to 20%. Conditions that increase metabolic stress (eg, critical\nillness, infection, inflammation, trauma, surgery) can increase RMR but rarely by > 50%.\nThe Mifflin-St. Jeor equation estimates RMR more precisely and with fewer errors than the commonly\nused Harris-Benedict equation, usually providing results that are within 20% of those measured by\nindirect calorimetry. The Mifflin-St. Jeor equation estimates RMR as follows:\nMen\n: kcal / day = 66 + (13.7 \u00d7 wt[kg]) + (5 \u00d7 height[cm]) - (6.8 \u00d7 age)\nWomen\n: kcal / day = 665 + (9.6 \u00d7 wt[kg]) + (1.8 \u00d7 height[cm]) - (4.7 \u00d7 age)\nTEE can be estimated by adding about 10% (for sedentary people) to about 40% (for people who are\ncritically ill) to RMR.\nProtein requirements:\n For healthy people, protein requirements are estimated at 0.8 g/kg/day.\nHowever, for patients with metabolic stress or kidney failure and for elderly patients, requirements may be\nhigher (see\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 3. Nutritional Support\n69"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 17, "chroma:document": "Table 3-1\n).\nAssessing Response to Nutritional Support\nThere is no gold standard to assess response. Clinicians commonly use indicators of lean body mass\nsuch as the following:\n\u2022 Body mass index (BMI)\n\u2022 Body composition analysis\n\u2022 Body fat distribution (see pp.\n11\n and \n58\n)\nNitrogen balance, response to skin antigens, muscle strength measurement, and indirect calorimetry can\nalso be used.\n[\nTable 3-1.\n Estimated Adult Daily Protein Requirement]\nNitrogen balance,\n which reflects the balance between protein needs and supplies, is the difference\nbetween amount of nitrogen ingested and amount lost. A positive balance (ie, more ingested than lost)\nimplies adequate intake. Precise measurement is impractical, but estimates help assess response to\nnutritional support. Nitrogen intake is estimated from protein intake: nitrogen (g) equals protein (g)/6.25.\nEstimated nitrogen losses consist of urinary nitrogen losses (estimated by measuring urea nitrogen\ncontent of an accurately obtained 24-h urine collection) plus stool losses (estimated at 1 g/day if stool is\nproduced; negligible if stool is not produced) plus insensible and other unmeasured losses (estimated at\n3 g).\nResponse to skin antigens\n, a measure of delayed hypersensitivity, often increases to normal as\nundernourished patients respond to nutritional support. However, other factors can affect response to\nskin antigens.\nMuscle strength\n indirectly reflects increases in lean body mass. It can be measured quantitatively, by\nhand-grip dynamometry, or electrophysiologically (typically by stimulating the ulnar nerve with an\nelectrode).\nLevels of acute-phase reactant\n serum proteins (particularly short-lived proteins such as prealbumin\n[transthyretin], retinol-binding protein, and transferrin) sometimes correlate with improved nutritional\nstatus, but these levels correlate better with inflammatory conditions.\nEnteral Tube Nutrition\nEnteral tube nutrition is indicated for patients who have a functioning GI tract but cannot ingest enough\nnutrients orally because they are unable or unwilling to take oral feedings. Compared with parenteral\nnutrition, enteral nutrition has the following advantages:\n\u2022 Better preservation of the structure and function of the GI tract\n\u2022 Lower cost\n\u2022 Probably fewer complications, particularly infections\nSpecific indications\n for enteral nutrition include the following:\n\u2022 Prolonged anorexia\n\u2022 Severe protein-energy undernutrition\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 3. Nutritional Support\n70"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 18, "chroma:document": "\u2022 Coma or depressed sensorium\n\u2022 Liver failure\n\u2022 Inability to take oral feedings due to head or neck trauma or neurologic disorders\n\u2022 Critical illnesses (eg, burns) causing metabolic stress\nOther indications may include bowel preparation for surgery in seriously ill or undernourished patients,\nclosure of enterocutaneous fistulas, and small-bowel adaptation after massive intestinal resection or in\ndisorders that may cause malabsorption (eg, Crohn's disease).\nProcedure:\n If tube feeding is needed for \u2264 4 to 6 wk, a small-caliber, soft nasogastric or nasoenteric (eg,\nnasoduodenal) tube made of silicone or polyurethane is usually used. If a nasal injury or deformity makes\nnasal placement difficult, an orogastric or other oroenteric tube can be placed.\nTube feeding for > 4 to 6 wk usually requires a gastrostomy or jejunostomy tube, placed endoscopically,\nsurgically, or radiologically. Choice depends on physician capabilities and patient preference.\nJejunostomy tubes are useful for patients with contraindications to gastrostomy (eg, gastrectomy, bowel\nobstruction proximal to the jejunum). However, these tubes do not pose less risk of tracheobronchial\naspiration than gastrostomy tubes, as is often thought. Jejunostomy tubes are easily dislodged and are\nusually used only for inpatients.\nFeeding tubes are surgically placed if endoscopic and radiologic placement is unavailable, technically\nimpossible, or unsafe (eg, because of overlying bowel). Open or laparoscopic techniques can be used.\nFormulas:\n Liquid formulas commonly used include feeding modules and polymeric or other specialized\nformulas.\nFeeding modules\n are commercially available products that contain a single nutrient, such as proteins,\nfats, or carbohydrates. Feeding modules may be used individually to treat a specific deficiency or\ncombined with other formulas to completely satisfy nutritional requirements.\nPolymeric formulas\n (including blenderized food and milk-based or lactose-free commercial formulas)\nare commercially available and generally provide a complete, balanced diet. For oral or tube feedings,\nthey are usually preferred to feeding modules. In hospitalized patients, lactose-free formulas are the most\ncommonly used polymeric formulas. However, milk-based formulas tend to taste better than lactose-free\nformulas. Patients with lactose intolerance may be able to tolerate milk-based formulas given slowly by\ncontinuous infusion.\nSpecialized formulas\n include hydrolyzed protein or sometimes amino acid formulas, which are used for\npatients who have difficulty digesting complex proteins. However, these formulas are expensive and\nusually unnecessary. Most patients with pancreatic insufficiency, if \ngiven enzymes, and most patients with\nmalabsorption can digest complex proteins. Other specialized formulas (eg, calorie- and protein-dense\nformulas for patients whose fluids are restricted, fiber-enriched formulas for constipated patients) may be\nhelpful.\nAdministration:\n Patients should be sitting upright at 30 to 45\u00b0 during tube feeding and for 1 to 2 h\nafterward to minimize incidence of nosocomial aspiration pneumonia and to allow gravity to help propel\nthe food. Tube feedings are given in boluses several times a day or by continuous infusion. Bolus feeding\nis more physiologic and may be preferred for patients with diabetes. Continuous infusion is necessary if\nboluses cause nausea.\n[\nTable 3-2.\n Complications of Enteral Tube Nutrition]\nFor bolus feeding, total daily volume is divided into 4 to 6 separate feedings, which are injected through\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 3. Nutritional Support\n71"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 19, "chroma:document": "the tube with a syringe or infused by gravity from an elevated bag. After feedings, the tube is flushed with\nwater to prevent clogging.\nNasogastric or nasoduodenal tube feeding\n often causes diarrhea initially; thus, feedings are usually\nstarted with small amounts of dilute preparations and increased as tolerated. Most formulas contain 0.5,\n1, or 2 kcal/mL. Formulas with higher caloric concentration (less water per calorie) may cause decreased\ngastric emptying and thus higher gastric residuals than when more dilute formulas with the same number\nof calories are used. Initially, a 1-kcal/mL commercially prepared solution may be given undiluted at 50\nmL/h or, if patients have not been fed for a while, at 25 mL/h. Usually, these solutions do not supply\nenough water, particularly if vomiting, diarrhea, sweating, or fever has increased water loss. Extra water\nis supplied as boluses via the feeding tube or IV. After a few days, the rate or concentration can be\nincreased as needed to meet caloric and water needs.\nJejunostomy tube feeding\n requires greater dilution and smaller volumes. Feeding usually begins at a\nconcentration of \u2264 0.5 kcal/mL and a rate of 25 mL/h. After a few days, concentrations and volumes can\nbe increased to eventually meet caloric and water needs. Usually, the maximum that can be tolerated is\n0.8 kcal/mL at 125 mL/h, providing 2400 kcal/day.\nComplications:\n Complications are common and can be serious (see \nTable 3-2\n).\nTotal Parenteral Nutrition\nParenteral nutrition is by definition given IV.\nPartial parenteral nutrition\n supplies only part of daily nutritional requirements, supplementing oral\nintake. Many hospitalized patients are given dextrose or amino acid solutions by this method.\nTotal parenteral nutrition\n (TPN) supplies all daily nutritional requirements. TPN can be used in the\nhospital or at home. Because TPN solutions are concentrated and can cause thrombosis of peripheral\nveins, a central venous catheter is usually required.\nParenteral nutrition should not be used routinely in patients with an intact GI tract. Compared with enteral\nnutrition, it causes more complications, does not preserve GI tract structure and function as well, and is\nmore expensive.\nIndications:\n TPN may be the only feasible option for patients who do not have a functioning GI tract or\nwho have disorders requiring complete bowel rest, such as the following:\n\u2022 Some stages of Crohn's disease or ulcerative colitis\n\u2022 Bowel obstruction\n\u2022 Certain pediatric GI disorders (eg, congenital GI anomalies, prolonged diarrhea regardless of its cause)\n\u2022 Short bowel syndrome due to surgery\nNutritional content:\n TPN requires water (30 to 40 mL/kg/day), energy (30 to 60 kcal/kg/day, depending\non energy expenditure), amino acids (1 to 2.0 g/kg/day, depending on the degree of catabolism), essential\nfatty acids, vitamins, and minerals (see\nTable 3-3\n). Children who need TPN may have different fluid requirements and need more energy (up to\n120 kcal/kg/day) and amino acids (up to 2.5 or 3.5 g/kg/day).\nBasic TPN solutions are prepared using sterile techniques, usually in liter batches according to standard\nformulas. Normally, 2 L/day of the standard solution is needed. Solutions may be modified based on\nlaboratory results, underlying disorders, hypermetabolism, or other factors.\nMost calories are supplied as carbohydrate. Typically, about 4 to 5 mg/kg/day of dextrose is given.\nStandard solutions contain up to about 25% dextrose, but the amount and concentration depend on other\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 3. Nutritional Support\n72"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 20, "chroma:document": "factors, such as metabolic needs and the proportion of caloric needs that are supplied by lipids.\nCommercially available lipid emulsions are often added to supply essential fatty acids and triglycerides;\n20 to 30% of total calories are usually supplied as lipids. However, withholding lipids and their calories\nmay help obese patients mobilize endogenous fat stores, increasing insulin sensitivity.\nSolutions:\n Many solutions are commonly used. Electrolytes can be added to meet the patient's needs.\nSolutions vary depending on other disorders present and patient age, as for the following:\n\u2022 For renal insufficiency not being treated with dialysis or for liver failure: Reduced protein content and a\nhigh percentage of essential amino acids\n\u2022 For heart or kidney failure: Limited volume (liquid) intake\n\u2022 \nFor respiratory failure: A lipid emulsion that provides most of nonprotein calories to minimize CO\n2\nproduction by carbohydrate metabolism\n\u2022 For neonates: Lower dextrose concentrations (17 to 18%)\nBeginning TPN administration:\n Because the central venous catheter needs to remain in place for a\nlong time, strict sterile technique must be used during insertion and maintenance. The TPN line should\nnot be used for any other purpose. External tubing should be changed every 24 h with the first bag of the\nday. In-line filters have not been shown to decrease complications. Dressings should be kept sterile and\nare usually changed every 48 h using strict sterile techniques. If TPN is given outside the hospital,\npatients must be taught to recognize symptoms of infection, and qualified home nursing must be\narranged.\nThe solution is started slowly at 50% of the calculated requirements, using 5% dextrose to make up the\nbalance of fluid requirements. Energy and nitrogen should be given simultaneously. The amount of\nregular insulin given (added directly to the TPN solution) depends on the plasma glucose level; if the\nlevel is normal and the final solution contains 25% dextrose, the usual starting dose is 5 to 10 units of\nregular insulin/L of TPN fluid.\nMonitoring:\n Progress should be followed on a flowchart. An interdisciplinary nutrition team, if available,\nshould monitor patients. Weight, CBC, electrolytes, and BUN should be monitored often (eg, daily for\ninpatients). Plasma glucose should be monitored every 6 h until patients and glucose levels become\nstable. Fluid intake and output should be monitored continuously. When patients become stable, blood\ntests can be done much less often.\nLiver function tests should be done. Plasma proteins (eg, serum albumin, possibly transthyretin or retinol-\nbinding protein), PT, plasma and urine osmolality, and Ca, Mg, and phosphate should be measured\ntwice/wk. Changes in transthyretin and retinol-binding protein reflect overall clinical status rather than\nnutritional status alone. If possible, blood tests should not be done during glucose infusion. Full nutritional\nassessment (including BMI calculation and anthropometric measurements\u2014see pp. \n11\n and \n58\n) should be\nrepeated at 2-wk intervals.\nComplications:\n About 5 to 10% of patients have complications related to central venous access.\n[\nTable 3-3.\n Basic Adult Daily Requirements for Total Parenteral Nutrition]\nCatheter-related sepsis occurs in about \u2265 50% of patients. Glucose abnormalities (hyperglycemia or\nhypoglycemia) or liver dysfunction occurs in > 90% of patients.\nGlucose abnormalities\n are common. Hyperglycemia can be avoided by monitoring plasma glucose\noften, adjusting the insulin dose in the TPN solution and giving subcutaneous insulin as needed.\nHypoglycemia can be precipitated by suddenly stopping constant concentrated dextrose infusions.\nTreatment depends on the degree of hypoglycemia. Short-term hypoglycemia may be reversed with 50%\ndextrose IV; more prolonged hypoglycemia may require infusion of 5 or 10% dextrose for 24 h before\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 3. Nutritional Support\n73"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 21, "chroma:document": "resuming TPN via the central venous catheter.\nHepatic complications\n include liver dysfunction, painful hepatomegaly, and hyperammonemia. They can\ndevelop at any age but are most common among infants, particularly premature ones (whose liver is\nimmature).\n\u2022 Liver dysfunction may be transient, evidenced by increased transaminases, bilirubin, and alkaline\nphosphatase; it commonly occurs when TPN is started. Delayed or persistent elevations may result\nfrom excess amino acids. Pathogenesis is unknown, but cholestasis and inflammation may contribute.\nProgressive fibrosis occasionally develops. Reducing protein delivery may help.\n\u2022 Painful hepatomegaly suggests fat accumulation; carbohydrate delivery should be reduced.\n\u2022 Hyperammonemia can develop in infants, causing lethargy, twitching, and generalized seizures. Arginine\nsupplementation at 0.5 to 1.0 mmol/kg/day can correct it.\nIf infants develop any hepatic complication, limiting amino acids to 1.0 g/kg/day may be necessary.\nAbnormalities of serum electrolytes and minerals\n should be corrected by modifying subsequent\ninfusions or, if correction is urgently required, by beginning appropriate peripheral vein infusions. Vitamin\nand mineral deficiencies are rare when solutions are given correctly. Elevated BUN may reflect\ndehydration, which can be corrected by giving free water as 5% dextrose via a peripheral vein.\nVolume overload\n (suggested by > 1 kg/day weight gain) may occur when patients have high daily\nenergy requirements and thus require large fluid volumes.\nMetabolic bone disease\n, or bone demineralization (osteoporosis or osteomalacia), develops in some\npatients given TPN for > 3 mo. The mechanism is unknown. Advanced disease can cause severe\nperiarticular, lower-extremity, and back pain. Temporarily or permanently stopping TPN is the only known\ntreatment.\nAdverse reactions to lipid emulsions\n (eg, dyspnea, cutaneous allergic reactions, nausea, headache,\nback pain, sweating, dizziness) are uncommon but may occur early, particularly if lipids are given at > 1.0\nkcal/kg/h. Temporary hyperlipidemia may occur, particularly in patients with kidney or liver failure;\ntreatment is usually not required. Delayed adverse reactions to lipid emulsions include hepatomegaly, mild\nelevation of liver enzymes, splenomegaly, thrombocytopenia, leukopenia, and, especially in premature\ninfants with respiratory distress syndrome, pulmonary function abnormalities. Temporarily or permanently\nslowing or stopping lipid emulsion infusion may prevent or minimize these adverse reactions.\nGallbladder complications\n include cholelithiasis, gallbladder sludge, and cholecystitis. These\ncomplications can be caused or worsened by prolonged gallbladder stasis. Stimulating contraction by\nproviding about 20 to 30% of calories as fat and stopping glucose infusion several hours a day is helpful.\nOral or enteral intake also helps. Treatment with metronidazole, ursodeoxycholic acid, phenobarbital, or\ncholecystokinin helps some patients with cholestasis.\nNutritional Support for Dying or Severely Demented Patients\nAnorexia or loss of appetite is common among dying patients (see p. \n3485\n). Behavioral measures (eg,\nusing flexible feeding schedules, feeding slowly, giving small portions or favorite or strongly flavored\nfoods) can often increase oral intake. A small amount of a favorite alcoholic drink, given 30 min before\nmeals, may also help. Certain antidepressants, megestrol acetate, and dronabinol may stimulate appetite.\nMetoclopramide enhances gastric emptying, but it may take 1 to 2 wk to reach peak effectiveness.\nAdvanced dementia eventually leads to inability to eat; sometimes affected patients are given tube\nfeedings. However, there is no convincing evidence that tube feedings prolong life, provide comfort,\nimprove function, or prevent complications (eg, aspiration, pressure ulcers).\nTube feedings and parenteral nutrition cause discomfort and are usually not indicated for patients who"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 21, "chroma:document": "improve function, or prevent complications (eg, aspiration, pressure ulcers).\nTube feedings and parenteral nutrition cause discomfort and are usually not indicated for patients who\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 3. Nutritional Support\n74"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 22, "chroma:document": "are dying or too demented to eat. Forgoing nutritional support may be difficult for family members to\naccept, but they should understand that patients are usually more comfortable eating and drinking as they\nchoose. Sips of water and easy-to-swallow foods may be useful. Supportive care, including good oral\nhygiene (eg, brushing the teeth, moistening the oral cavity with swabs and ice chips as needed, applying\nlip salve), can physically and psychologically comfort the patients and the family members who provide\nthe care.\nCounseling may help family members who are dealing with anxieties about whether to use invasive\nnutritional support.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 3. Nutritional Support\n75"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 23, "chroma:document": "Chapter 4. Vitamin Deficiency, Dependency, and Toxicity\nIntroduction\nVitamins may be fat soluble (vitamins A, D, E, and K) or water soluble (B vitamins and vitamin C). The B\nvitamins include biotin, folate, niacin, pantothenic acid, riboflavin (B\n2\n), thiamin (B\n1\n), B\n6\n (eg, pyridoxine),\nand B\n12\n (cobalamins). For dietary requirements, sources, functions, effects of deficiencies and toxicities,\nblood levels, and usual therapeutic dosages for vitamins, see\nTables 4-1\n and\n4-2\n.\nDietary requirements for vitamins (and other nutrients) are expressed as daily recommended intake (DRI).\nThere are 3 types of DRI:\n\u2022 \nRecommended daily allowance (RDA):\n RDAs are set to meet the needs of 97 to 98% of healthy\npeople.\n\u2022 \nAdequate intake (AI):\n When data to calculate an RDA are insufficient, AIs are based on observed or\nexperimentally determined estimates of nutrient intake by healthy people.\n\u2022 \nTolerable upper intake level (UL):\n ULs are the largest amount of a nutrient that most adults can\ningest daily without risk of adverse health effects.\nIn developed countries, vitamin deficiencies result mainly from poverty, food faddism, drugs (see p. \n7\n and\nTable 4-3\n), alcoholism, or prolonged and inadequately supplemented parenteral feeding. Mild vitamin\ndeficiency is common among frail and institutionalized elderly people who have protein-energy\nundernutrition. In developing countries, deficiencies can result from lack of access to nutrients.\nDeficiencies of water-soluble vitamins (except vitamin B\n12\n) may develop after weeks to months of\nundernutrition. Deficiencies of fat-soluble vitamins and of vitamin B\n12\n take > 1 yr to develop because the\nbody stores them in relatively large amounts. Intake of vitamins sufficient to prevent classic vitamin\ndeficiencies (like scurvy or beriberi) may not be adequate for optimum health. This area remains one of\ncontroversy and active research.\nVitamin dependency results from a genetic defect involving metabolism of a vitamin. In some cases,\nvitamin doses as high as 1000 times the DRI improve function of the altered metabolic pathway. Vitamin\ntoxicity (hypervitaminosis) usually results from taking megadoses of vitamin A, D, C, B\n6\n, or niacin.\nBecause many people eat irregularly, foods alone may provide suboptimal amounts of some vitamins. In\nthese cases, the risk of certain cancers or other disorders may be increased. Because of this risk, routine\ndaily multivitamin supplements are sometimes recommended.\nBiotin and Pantothenic Acid\nBiotin acts as a coenzyme for carboxylation reactions essential to fat and carbohydrate metabolism.\nAdequate intake for adults is 30 \n\u03bc\ng/day. Pantothenic acid is widely distributed in foods; it is an essential\ncomponent of coenzyme A. Adults probably require about 5 mg/day. A beneficial role for pantothenic acid\nsupplementation in lipid metabolism, RA, or athletic performance remains unproved. Isolated deficiency of\nbiotin or pantothenic acid virtually never occurs.\nFolate\nFolate (folic acid) is now added to enriched grain foods in the US. Folate is also plentiful in various plant\nfoods and meats, but its bioavailability is greater when it is in supplements\n[\nTable 4-1.\n Recommended Daily Intakes for Vitamins]\nor enriched foods than when it occurs naturally in food.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n76"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 24, "chroma:document": "Folates are involved in RBC maturation and synthesis of purines and pyrimidines. They are required for\ndevelopment of the fetal nervous system. Absorption occurs in the duodenum and upper jejunum.\nEnterohepatic circulation of folate occurs. Folate supplements\n[\nTable 4-2.\n Sources, Functions, and Effects of Vitamins]\ndo not protect against coronary artery disease or stroke (by lowering homocysteine levels); their role in\nreducing the risk of various cancers is unclear. The upper limit for folate intake is 1000 \n\u03bc\ng; higher doses\n(up to 5 mg) are recommended for women who have had a baby with a neural tube defect. Folate is\nessentially nontoxic.\nFolate Deficiency\nFolate deficiency is common. It may result from inadequate intake, malabsorption, or use of various drugs.\nDeficiency causes megaloblastic anemia (indistinguishable from that due to vitamin B\n12\n deficiency).\nMaternal deficiency increases the risk of neural tube birth defects. Diagnosis requires laboratory testing\nto confirm. Measurement of neutrophil hypersegmentation is sensitive and readily available. Treatment\nwith oral folate is usually successful.\nEtiology and Pathophysiology\nThe most common causes are inadequate intake (usually in patients with undernutrition or alcoholism),\nincreased demand (eg, due to pregnancy or breastfeeding), and impaired absorption (eg, in tropical\nsprue, due to certain drugs). Deficiency can also result from inadequate bioavailability and increased\nexcretion (see\nTable 4-4\n).\nProlonged cooking destroys folate, predisposing to inadequate intake. Intake is sometimes barely\nadequate (eg, in alcoholics). Liver stores provide only a several-month supply.\nAlcohol interferes with folate absorption, metabolism, renal excretion, and enterohepatic reabsorption, as\nwell as intake. 5-Fluorouracil, metformin, methotrexate, phenobarbital, phenytoin, sulfasalazine,\ntriamterene, and trimethoprim impair folate metabolism.\nIn the US, many dietary staples (eg, cereals, grain products) are routinely enriched with folate, tending to\nreduce risk of deficiency.\n[\nTable 4-3.\n Potential Vitamin-Drug Interactions]\nSymptoms and Signs\nFolate deficiency may cause glossitis, diarrhea, depression, and confusion. Anemia may develop\ninsidiously and, because of compensatory mechanisms, be more severe than symptoms suggest.\nFolate deficiency during pregnancy increases the risk of fetal neural tube defects and perhaps other brain\ndefects (see p. \n2992\n).\nDiagnosis\n\u2022 CBC and serum vitamin B\n12\n and folate levels\nCBC may indicate megaloblastic anemia indistinguishable from that of vitamin B\n12\n deficiency. If serum\nfolate is < 3 \n\u03bc\ng/L or ng/mL (< 7 nmol/L), deficiency is likely. Serum folate reflects folate status unless\nintake has recently increased or decreased. If intake has changed, erythrocyte (RBC) folate level better\nreflects tissue stores. A level of < 140 \n\u03bc\ng/L or ng/mL (< 305 nmol/L) indicates inadequate status. Also, an\nincrease in the homocysteine level suggests tissue folate deficiency (but the level is also affected by\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n77"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 25, "chroma:document": "vitamin B\n12\n and vitamin B\n6\n levels, renal insufficiency, and genetic factors). A normal methylmalonic acid\n(MMA) level may differentiate folate deficiency from vitamin B\n12\n deficiency because MMA levels rise in\nvitamin B\n12\n deficiency but not in folate deficiency.\nTreatment\n\u2022 Supplemental oral folate\nFolate 400 to 1000 \n\u03bc\ng po once/day replenishes tissues and is usually successful even if deficiency has\nresulted from malabsorption. The normal requirement is 400 \n\u03bc\ng/day.\n[\nTable 4-4.\n Causes of Folate Deficiency]\n(CAUTION: \nIn patients with megaloblastic anemia, vitamin B\n12\n deficiency must be ruled out before\ntreating with folate. If vitamin B\n12\n deficiency is present, folate supplementation can alleviate the\nanemia but does not reverse and may even worsen neurologic deficits\n.) For pregnant women, the\nrecommended daily allowance (RDA) is 600 \n\u03bc\ng/day. For women who have had a fetus or infant with a\nneural tube defect, the recommended dose is 1000 to 5000 \n\u03bc\ng/day.\nNiacin\nNiacin (nicotinic acid, nicotinamide) derivatives include nicotinamide adenine dinucleotide (NAD) and\nnicotinamide adenine dinucleotide phosphate (NADP), which are coenzymes in oxidation-reduction\nreactions. They are vital in cell metabolism. Because dietary tryptophan can be metabolized to niacin,\nfoods rich in tryptophan (eg, dairy products) can compensate for inadequate dietary niacin.\nNiacin Deficiency\nDietary niacin deficiency (causing pellagra) is uncommon in developed countries. Clinical\nmanifestations include the \"three Ds\": localized pigmented rash (dermatitis); gastroenteritis\n(diarrhea); and widespread neurologic deficits, including cognitive decline (dementia).\nDiagnosis is usually clinical, and dietary supplementation (oral or, if needed, IM) is usually\nsuccessful.\nEtiology\nPrimary deficiency results from extremely inadequate intake of both niacin and tryptophan, which usually\noccurs in areas where maize (Indian corn) constitutes a substantial part of the diet. Bound niacin, found in\nmaize, is not assimilated in the GI tract unless it has been previously treated with alkali, as when tortillas\nare prepared. Corn protein is also deficient in tryptophan. The high incidence of pellagra in India among\npeople who eat millet with a high leucine content has led to the hypothesis that amino acid imbalance may\ncontribute to deficiency. Deficiencies of protein and many B vitamins commonly accompany primary niacin\ndeficiency.\nSecondary deficiency may be due to diarrhea, cirrhosis, or alcoholism. Pellagra also may occur in\ncarcinoid syndrome (tryptophan is diverted to form 5-hydroxytryptophan and serotonin) and in Hartnup\ndisease (absorption of tryptophan by the intestine and kidneys is defective).\nSymptoms and Signs\nPellagra is characterized by skin, mucous membrane, CNS, and GI symptoms. Advanced pellagra can\ncause a symmetric photosensitive rash, stomatitis, glossitis, diarrhea, and mental aberrations. Symptoms\nmay appear alone or in combination.\nSkin symptoms\n include several types of lesions, which are usually bilaterally symmetric. The distribution\nof lesions\u2014at pressure points or sun-exposed skin\u2014is more pathognomonic than the form of the lesions.\nLesions can develop in a glovelike distribution on the hands (pellagrous glove) or in a boot-shaped\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n78"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 26, "chroma:document": "distribution on the feet and legs (pellagrous boot). Sunlight causes Casal's necklace and butterfly-shaped\nlesions on the face.\nMucous membrane symptoms\n affect primarily the mouth but may also affect the vagina and urethra.\nGlossitis and stomatitis characterize acute deficiency. As the deficiency progresses, the tongue and oral\nmucous membranes become reddened, followed by pain in the mouth, increased salivation, and edema of\nthe tongue. Ulcerations may appear, especially under the tongue, on the mucosa of the lower lip, and\nopposite the molar teeth.\nGI symptoms\n early in the deficiency include burning in the pharynx and esophagus and abdominal\ndiscomfort and distention. Constipation is common. Later, nausea, vomiting, and diarrhea may occur.\nDiarrhea is often bloody because of bowel hyperemia and ulceration.\nCNS symptoms\n include psychosis, encephalopathy (characterized by impaired consciousness), and\ncognitive decline (dementia). Psychosis is characterized by memory impairment, disorientation, confusion,\nand confabulation; the predominant symptom may be excitement, depression, mania, delirium, or\nparanoia.\nDiagnosis\n\u2022 Clinical evaluation\nDiagnosis is clinical and may be straightforward when skin and mouth lesions, diarrhea, delirium, and\ndementia occur simultaneously. More often, the presentation is not so specific. Differentiating the CNS\nchanges from those in thiamin deficiency is difficult. A history of a diet lacking niacin and tryptophan may\nhelp establish the diagnosis. A favorable response to treatment with niacin can usually \nconfirm it. If\navailable, laboratory testing can help confirm the diagnosis, particularly when the diagnosis is otherwise\nunclear. Urinary excretion of N\n1\n-methylnicotinamide (NMN) is decreased; < 0.8 mg/day (< 5.8 \n\u03bc\nmol/day)\nsuggests a niacin deficiency.\nTreatment\n\u2022 Nicotinamide and other nutrients\nBecause multiple deficiencies are common, a balanced diet, including other B vitamins (particularly\nriboflavin and pyridoxine), is needed. Nicotinamide is usually used to treat deficiency, because\nnicotinamide, unlike nicotinic acid (the most common form of niacin), does not cause flushing, itching,\nburning, or tingling sensations. Nicotinamide is given in doses ranging from 40 to 250 mg/day po in\ndivided doses 3 to 4 times a day.\nNiacin Toxicity\nNiacin (nicotinic acid) in large amounts is sometimes used to lower low-density lipoprotein\n(LDL) cholesterol and triglyceride levels and to increase high-density lipoprotein (HDL)\ncholesterol levels. Symptoms may include flushing and, rarely, hepatotoxicity.\nImmediate- and sustained-release preparations of niacin (but not nicotinamide) may improve lipid levels.\nFlushing, which is prostaglandin-mediated, is more common with immediate-release preparations. It may\nbe more intense after alcohol ingestion, aerobic activity, sun exposure, and consumption of spicy foods.\nFlushing is minimized if niacin is taken after meals or if aspirin (325 mg) is taken 30 to 45 min before\nniacin. The chance of severe flushing can be reduced by starting immediate-release niacin at a low dose\n(eg, 50 mg tid) and increasing it very slowly. At intermediate doses (1000 mg/day), triglyceride levels\ndecrease 15 to 20%, and HDL cholesterol levels increase 15 to 30%. Reductions in LDL cholesterol are\nmodest (< 10%). Higher doses of niacin (3000 mg/day) reduce LDL cholesterol 15 to 20% but may cause\njaundice, abdominal discomfort, blurred vision, worsening of hyperglycemia, and precipitation of\npreexisting gout. People with a liver disorder probably should not take high-dose niacin.\nHepatotoxicity may be more common with some sustained-release preparations. Some authorities\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n79"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 27, "chroma:document": "recommend checking levels of uric acid, serum glucose, and plasma transaminases every 6 to 8 wk until\nthe dose of niacin has been stabilized.\nRiboflavin\nRiboflavin (vitamin B\n2\n) is involved in carbohydrate metabolism as an essential coenzyme in many\noxidation-reduction reactions. Riboflavin is essentially nontoxic.\nRiboflavin Deficiency\nRiboflavin deficiency usually occurs with other B-vitamin deficiencies. Symptoms and signs\ninclude sore throat, lesions of the lips and mucosa of the mouth, glossitis, conjunctivitis,\nseborrheic dermatitis, and normochromicnormocytic anemia. Diagnosis is usually clinical.\nTreatment consists of oral or, if needed, IM riboflavin.\nPrimary riboflavin deficiency results from inadequate intake of fortified cereals, milk, and other animal\nproducts. The most common causes of secondary deficiency are chronic diarrhea, malabsorption\nsyndromes, liver disorders, hemodialysis, peritoneal dialysis, long-term use of barbiturates, and chronic\nalcoholism.\nSymptoms and Signs\nThe most common signs are pallor and maceration of the mucosa at the angles of the mouth (angular\nstomatitis) and vermilion surfaces of the lips (cheilosis), eventually replaced by superficial linear fissures.\nThe fissures can become infected with \nCandida albicans\n, causing grayish white lesions (perleche). The\ntongue may appear magenta. Seborrheic dermatitis develops, usually affecting the nasolabial folds, ears,\neyelids, and scrotum or labia majora. These areas become red, scaly, and greasy.\nRarely, neovascularization and keratitis of the cornea occur, causing lacrimation and photophobia.\nDiagnosis\nThe lesions characteristic of riboflavin deficiency are nonspecific. Riboflavin deficiency should be\nsuspected if characteristic signs develop in a patient with other B vitamin deficiencies. Diagnosis can be\nconfirmed by a therapeutic trial or laboratory testing, usually by measuring urinary excretion of riboflavin.\nTreatment\nRiboflavin 5 to 10 mg/day po is given until recovery. Other water-soluble vitamins should also be given.\nThiamin\nThiamin (vitamin B\n1\n) is widely available in the diet. Thiamin is involved in carbohydrate, fat, amino acid,\nglucose, and alcohol metabolism. Thiamin is essentially nontoxic.\nThiamin Deficiency\nThiamin deficiency (causing beriberi) is most common among people subsisting on white rice\nor highly refined carbohydrates in developing countries and among alcoholics. Symptoms\ninclude diffuse polyneuropathy, high-output heart failure, and Wernicke-Korsakoff syndrome.\nThiamin is given to help diagnose and treat the deficiency.\nEtiology\nPrimary thiamin deficiency is caused by inadequate intake of thiamin. It is commonly due to a diet of\nhighly refined carbohydrates (eg, polished rice, white flour, white sugar). It also develops when intake of\nother nutrients is inadequate; it often occurs with other B vitamin deficiencies.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n80"}


created_at: 2025-06-20 08:54:40
topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 28, "chroma:document": "Secondary thiamin deficiency is caused by increased demand (eg, due to hyperthyroidism, pregnancy,\nbreastfeeding, strenuous exercise, or fever), impaired absorption (eg, due to prolonged diarrhea), or\nimpaired metabolism (eg, due to hepatic insufficiency). In alcoholics, many mechanisms contribute to\nthiamin deficiency; they include decreased intake, impaired absorption and use, increased demand, and\npossibly an apoenzyme defect.\nPathophysiology\nDeficiency causes degeneration of peripheral nerves, thalamus, mammillary bodies, and cerebellum.\nCerebral blood flow is markedly reduced, and vascular resistance is increased.\nThe heart may become dilated; muscle fibers become swollen, fragmented, and vacuolized, with\ninterstitial spaces dilated by fluid. Vasodilation occurs and can result in edema in the feet and legs.\nArteriovenous shunting of blood increases. Eventually, high-output heart failure may occur.\nSymptoms and Signs\nEarly symptoms are nonspecific: fatigue, irritability, poor memory, sleep disturbances, precordial pain,\nanorexia, and abdominal discomfort.\nDry beriberi\n refers to peripheral neurologic deficits due to thiamin deficiency. These deficits are bilateral\nand roughly symmetric, occurring in a stocking-glove distribution. They affect predominantly the lower\nextremities, beginning with paresthesias in the toes, burning in the feet (particularly severe at night),\nmuscle cramps in the calves, pains in the legs, and plantar dysesthesias. Calf muscle tenderness,\ndifficulty rising from a squatting position, and decreased vibratory sensation in the toes are early signs.\nMuscle wasting occurs. Continued deficiency worsens polyneuropathy, which can eventually affect the\narms.\nWernicke-Korsakoff syndrome,\n which combines Wernicke's encephalopathy (see p. \n1522\n) and\nKorsakoff's psychosis (see p. \n1523\n), occurs in some alcoholics who do not consume foods fortified with\nthiamin. Wernicke's encephalopathy consists of psychomotor slowing or apathy, nystagmus, ataxia,\nophthalmoplegia, impaired consciousness, and, if untreated, coma and death. It probably results from\nsevere acute deficiency superimposed on chronic deficiency. Korsakoff's psychosis consists of mental\nconfusion, dysphonia, and confabulation with impaired memory of recent events. It probably results from\nchronic deficiency and may develop after repeated episodes of Wernicke's encephalopathy.\nCardiovascular (wet) beriberi\n is myocardial disease due to thiamin deficiency. The first effects are\nvasodilation, tachycardia, a wide pulse pressure, sweating, warm skin, and lactic acidosis. Later, heart\nfailure develops, causing orthopnea and pulmonary and peripheral edema. Vasodilation can continue,\nsometimes resulting in shock.\nInfantile beriberi\n occurs in infants (usually by age 3 to 4 wk) who are breastfed by thiamin-deficient\nmothers. Heart failure (which may occur suddenly), aphonia, and absent deep tendon reflexes are\ncharacteristic.\nBecause thiamin is necessary for glucose metabolism, glucose infusions may precipitate or worsen\nsymptoms of deficiency in thiamin-deficient people.\nDiagnosis\n\u2022 Favorable response to thiamin\nDiagnosis is usually based on a favorable response to treatment with thiamin in a patient with symptoms\nor signs of deficiency. Similar bilateral lower-extremity polyneuropathies due to other disorders (eg,\ndiabetes, alcoholism, vitamin B\n12\n deficiency, heavy metal poisoning) do not respond to thiamin. Single-\nnerve neuritides (mononeuropathies\u2014eg, sciatica) and multiple mononeuropathies (mononeuritis\nmultiplex) are unlikely to result from thiamin deficiency.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n81"}


created_at: 2025-06-20 08:54:40
topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 29, "chroma:document": "Electrolytes, including Mg, should be measured to exclude other causes. For confirmation in equivocal\ncases, erythrocyte transketolase activity and 24-h urinary thiamin excretion may be measured.\nDiagnosis of cardiovascular beriberi can be difficult if other disorders that cause heart failure are present.\nA therapeutic trial of thiamin can help.\nTreatment\n\u2022 Supplemental thiamin, with dose based on clinical manifestations\nEnsuring that dietary supplies of thiamin are adequate is important regardless of symptoms. Because IV\nglucose can worsen thiamin deficiency, alcoholics and others at risk of thiamin deficiency should receive\nIV thiamin 100 mg before receiving IV glucose solutions.\nFor mild polyneuropathy, thiamin 10 to 20 mg po once/day is given for 2 wk. For moderate or advanced\nneuropathy, the dose is 20 to 30 mg/day; it should be continued for several weeks after symptoms\ndisappear. For edema and congestion due to cardiovascular beriberi, thiamin 100 mg IV once/day is given\nfor several days. Heart failure is also treated.\nFor Wernicke-Korsakoff syndrome, thiamin 50 to 100 mg IM or IV bid must usually be given for several\ndays, followed by 10 to 20 mg once/day until a therapeutic response is obtained. Anaphylactic reactions\nto IV thiamin are rare. Symptoms of ophthalmoplegia may resolve in a day; improvement in patients with\nKorsakoff psychosis may take 1 to 3 mo. Recovery from neurologic deficits is often incomplete in\nWernicke-Korsakoff syndrome and in other forms of thiamin deficiency.\nBecause thiamin deficiency often occurs with other B vitamin deficiencies, multiple water-soluble vitamins\nare usually given for several weeks. Patients should continue to consume a nutritious diet, supplying 1 to\n2 times the daily recommended intake of vitamins; all alcohol intake should stop.\nVitamin A\nVitamin A (retinol) is required for the formation of rhodopsin, a photoreceptor pigment in the retina. Vitamin\nA helps maintain epithelial tissues. Normally, the liver stores 80 to 90% of the body's vitamin A. To use\nvitamin A, the body releases it into the circulation bound to prealbumin (transthyretin) and retinol-binding\nprotein. \n\u03b2\n-Carotene and other provitamin carotenoids, contained in green leafy and yellow vegetables\nand deep- or bright-colored fruits, are converted to vitamin A. Carotenoids are absorbed better from\nvegetables when they are cooked or homogenized and served with some fats or oils.\nRetinol activity equivalents (RAE) were developed because provitamin A carotenoids have less vitamin A\nactivity than preformed vitamin A; 1 \n\u03bc\ng retinol = 3.33 IU.\nSynthetic vitamin analogs (retinoids) are being used increasingly in dermatology. The possible protective\nrole of \n\u03b2\n-carotene, retinol, and retinoids against some epithelial cancers is under study. However, risk of\ncertain cancers may be increased after \n\u03b2\n-carotene supplementation.\nVitamin A Deficiency\nVitamin A deficiency can result from inadequate intake, fat malabsorption, or liver disorders.\nDeficiency impairs immunity and hematopoiesis and causes rashes and typical ocular effects\n(eg, xerophthalmia, night blindness). Diagnosis is based on typical ocular findings and low\nvitamin A levels. Treatment consists of vitamin A given orally or, if symptoms are severe or\nmalabsorption is the cause, parenterally.\nEtiology\nPrimary vitamin A deficiency is usually caused by prolonged dietary deprivation. It is endemic in areas\nsuch as southern and eastern Asia, where rice, devoid of \n\u03b2\n-carotene, is the staple food. Xerophthalmia\ndue to primary deficiency is a common cause of blindness among young children in developing countries.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n82"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 30, "chroma:document": "Secondary vitamin A deficiency may be due to decreased bioavailability of provitamin A carotenoids or to\ninterference with absorption, storage, or transport of vitamin A. Interference with absorption or storage is\nlikely in sprue, cystic fibrosis, pancreatic insufficiency, duodenal bypass, chronic diarrhea, bile duct\nobstruction, giardiasis, and cirrhosis. Vitamin A deficiency is common in prolonged protein-energy\nundernutrition not only because the diet is deficient but also because vitamin A storage and transport is\ndefective. In children with complicated measles, vitamin A can shorten the duration of the disorder and\nreduce the severity of symptoms and risk of death.\nSymptoms and Signs\nImpaired dark adaptation of the eyes, which can lead to night blindness, is an early symptom.\nXerophthalmia (which is nearly pathognomonic) results from keratinization of the eyes. It involves drying\n(xerosis) and thickening of the conjunctivae and corneas. Superficial foamy patches composed of\nepithelial debris and secretions on the exposed bulbar conjunctiva (Bitot's spots) develop. In advanced\ndeficiency, the cornea becomes hazy and can develop erosions, which can lead to its destruction\n(keratomalacia).\nKeratinization of the skin and of the mucous membranes in the respiratory, GI, and urinary tracts can\noccur. Drying, scaling, and follicular thickening of the skin and respiratory infections can result. Immunity\nis generally impaired.\nThe younger the patient, the more severe are the effects of vitamin A deficiency. Growth retardation and\ninfections are common among children. Mortality rate can exceed 50% in children with severe vitamin A\ndeficiency.\nDiagnosis\n\u2022 Serum retinol levels, clinical evaluation, and response to vitamin A\nOcular findings suggest the diagnosis. Dark adaptation can be impaired in other disorders (eg, zinc\ndeficiency, retinitis pigmentosa, severe refractive errors, cataracts, diabetic retinopathy). If dark\nadaptation is impaired, rod scotometry and electroretinography are done to determine whether vitamin A\ndeficiency is the cause.\nSerum levels of retinol are measured. Normal range is 28 to 86 \n\u03bc\ng/dL (1 to 3 \n\u03bc\nmol/L). However, levels\ndecrease only after the deficiency is advanced because the liver contains large stores of vitamin A. Also,\ndecreased levels may result from acute infection, which causes retinol-binding protein and transthyretin\n(also called prealbumin) levels to decrease transiently. A therapeutic trial of vitamin A may help confirm\nthe diagnosis.\nPrevention\nThe diet should include dark green leafy vegetables, deep- or bright-colored fruits (eg, papayas,\noranges), carrots, and yellow vegetables (eg, squash, pumpkin). Vitamin A-fortified milk and cereals, liver,\negg yolks, and fish liver oils are helpful. Carotenoids are absorbed better when consumed with some\ndietary fat. If milk allergy is suspected in infants, they should be given adequate vitamin A in formula\nfeedings. In developing countries, prophylactic supplements of vitamin A palmitate in oil 60,000 RAE\n(200,000 IU) po every 6 mo are advised for all children between 1 and 5 yr of age; infants < 6 mo can be\ngiven a one-time dose of 15,000 RAE (50,000 IU), and those aged 6 to 12 mo can be given a one-time\ndose of 30,000 RAE (100,000 IU).\nTreatment\n\u2022 Vitamin A palmitate\nDietary deficiency is traditionally treated with vitamin A palmitate in oil 60,000 IU po once/day for 2 days,\nfollowed by 4500 IU po once/day. If vomiting or malabsorption is present or xerophthalmia is probable, a\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n83"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 31, "chroma:document": "dose of 50,000 IU for infants < 6 mo, 100,000 IU for infants 6 to 12 mo, or 200,000 IU for children > 12 mo\nand adults should be given for 2 days, with a third dose at least 2 wk later. The same doses are\nrecommended for infants and children with complicated measles. Infants born of HIV-positive mothers\nshould receive 50,000 IU (15,000 RAE) within 48 h of birth. Prolonged daily administration of large doses,\nespecially to infants, must be avoided because toxicity may result.\nFor pregnant or breastfeeding women, prophylactic or therapeutic doses should not exceed 10,000 IU\n(3000 RAE)/day to avoid possible damage to the fetus or infant.\nVitamin A Toxicity\nVitamin A toxicity can be acute (usually due to accidental ingestion by children) or chronic. Both\ntypes usually cause headache and increased intracranial pressure. Acute toxicity also causes\nnausea and vomiting. Chronic toxicity also causes changes in skin, hair, and nails; abnormal\nliver test results; and, in a fetus, birth defects. Diagnosis is usually clinical. Unless birth defects\nare present, adjusting the dose almost always leads to complete recovery.\nAcute vitamin A toxicity in children may result from taking large doses (> 100,000 RAE [> 300,000 IU]),\nusually accidentally. In adults, acute toxicity has occurred when arctic explorers ingested polar bear or\nseal livers, which contain several million units of vitamin A.\nChronic toxicity in older children and adults usually develops after doses of > 30,000 RAE (> 100,000\nIU)/day have been taken for months. Megavitamin therapy is a possible cause, as are massive daily\ndoses (50,000 to 120,000 RAE [150,000 to 350,000 IU]) of vitamin A \nor its metabolites, which are\nsometimes given for nodular acne or other skin disorders. Adults who consume > 1500 RAE (> 4500\nIU)/day of vitamin A may develop osteoporosis. Infants who are given excessive doses (6,000 to 20,000\nRAE [18,000 to 60,000 IU]/day) of water-miscible vitamin A may develop toxicity within a few weeks. Birth\ndefects occur in children of women receiving isotretinoin (which is related to vitamin A) for acne treatment\nduring pregnancy.\nAlthough carotene is converted to vitamin A in the body, excessive ingestion of carotene causes\ncarotenemia, not vitamin A toxicity. Carotenemia is usually asymptomatic but may lead to carotenodermia,\nin which the skin becomes yellow. When taken as a supplement, \n\u03b2\n-carotene has been associated with\nincreased cancer risk; risk does not seem to increase when carotenoids are consumed in fruits and\nvegetables.\nSymptoms and Signs\nAlthough symptoms may vary, headache and rash usually develop during acute or chronic toxicity. Acute\ntoxicity causes increased intracranial pressure. Drowsiness, irritability, abdominal pain, nausea, and\nvomiting are common. Sometimes the skin subsequently peels.\nEarly symptoms of chronic toxicity are sparsely distributed, coarse hair; alopecia of the eyebrows; dry,\nrough skin; dry eyes; and cracked lips. Later, severe headache, pseudotumor cerebri, and generalized\nweakness develop. Cortical hyperostosis of bone and arthralgia may occur, especially in children.\nFractures may occur easily, especially in the elderly. In children, toxicity can cause pruritus, anorexia, and\nfailure to thrive. Hepatomegaly and splenomegaly may occur.\nIn carotenodermia, the skin (but not the sclera) becomes deep yellow, especially on the palms and soles.\nDiagnosis\n\u2022 Clinical evaluation\nDiagnosis is clinical. Blood vitamin levels correlate poorly with toxicity. However, if clinical diagnosis is\nequivocal, laboratory testing may help. In vitamin A toxicity, fasting serum retinol levels may increase from\nnormal (28 to 86 \n\u03bc\ng/dL [1 to 3 \n\u03bc\nmol/L]) to > 100 \n\u03bc\ng/dL (> 3.49 \n\u03bc\nmol/L), sometimes to > 2000 \n\u03bc\ng/dL (> 69.8\n\u03bc\nmol/L). Hypercalcemia is common.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n84"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 32, "chroma:document": "Differentiating vitamin A toxicity from other disorders may be difficult. Carotenodermia may also occur in\nsevere hypothyroidism and anorexia nervosa, possibly because carotene is converted to vitamin A more\nslowly.\nPrognosis\nComplete recovery usually occurs if vitamin A ingestion stops. Symptoms and signs of chronic toxicity\nusually disappear within 1 to 4 wk. However, birth defects in the fetus of a mother who has taken\nmegadoses of vitamin A are not reversible.\nTreatment\nVitamin A is stopped.\nVitamin B\n6\nVitamin B\n6\n includes a group of closely related compounds: pyridoxine, pyridoxal, and pyridoxamine. They\nare metabolized in the body to pyridoxal phosphate, which acts as a coenzyme in many important\nreactions in blood, CNS, and skin metabolism. Vitamin B\n6\n is important in heme and nucleic acid\nbiosynthesis and in lipid, carbohydrate, and amino acid metabolism.\nVitamin B\n6\n Deficiency and Dependency\nBecause vitamin B\n6\n is present in most foods, dietary deficiency is rare. Secondary deficiency\nmay result from various conditions. Symptoms can include peripheral neuropathy, a pellagra-\nlike syndrome, anemia, and seizures, which, particularly in infants, may not resolve when\ntreated with anticonvulsants. Impaired metabolism (dependency) is rare; it causes various\nsymptoms, including seizures, intellectual disability, and anemia. Diagnosis is usually clinical;\nno laboratory test readily assesses vitamin B\n6\n status. Treatment consists of giving oral vitamin\nB\n6\n and, when possible, treating the cause.\nDietary deficiency, though rare, can develop because extensive processing can deplete foods of vitamin\nB\n6\n. Secondary deficiency most often results from protein-energy undernutrition, malabsorption,\nalcoholism, use of pyridoxine-inactivating drugs (eg, anticonvulsants, isoniazid, cycloserine, hydralazine,\ncorticosteroids, penicillamine), or excessive loss. Rarely, it results from increased metabolic demand (eg,\nin hyperthyroidism).\nRare inborn errors of metabolism can affect pyridoxine metabolism.\nThe role of vitamin B\n6\n deficiency in increasing plasma homocysteine levels and in contributing to vascular\ndisorders is under study.\nSymptoms and Signs\nDeficiency causes a pellagra-like syndrome, with seborrheic dermatitis, glossitis, and cheilosis, and, in\nadults, can cause depression, confusion, EEG abnormalities, and seizures. Rarely, deficiency or\ndependency causes seizures in infants. Seizures, particularly in infants, may be refractory to treatment\nwith anticonvulsants. Normocytic, microcytic, or sideroblastic anemia can also develop.\nDiagnosis\n\u2022 Clinical evaluation\nVitamin B\n6\n deficiency should be considered in any infant who has seizures, any patient who has seizures\nrefractory to treatment with anticonvulsants, and any patient with deficiencies of other B vitamins,\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n85"}


created_at: 2025-06-20 08:54:40
topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 33, "chroma:document": "particularly in patients with alcoholism or protein-energy undernutrition. Diagnosis is usually clinical.\nThere is no single accepted laboratory test of vitamin B\n6\n status; measurement of serum pyridoxal\nphosphate is most common.\nTreatment\n\u2022 Pyridoxine\n\u2022 Elimination of risk factors when possible\nFor secondary deficiency, causes (eg, use of pyridoxine-inactivating drugs, malabsorption) should be\ncorrected if possible. Usually, pyridoxine 50 to 100 mg po once/day corrects the deficiency in adults. Most\npeople taking isoniazid should also be given pyridoxine 30 to 50 mg/day. For deficiency due to increased\nmetabolic demand, amounts larger than the daily recommended intake may be required. For most cases\nof inborn errors of metabolism, high doses of pyridoxine may be effective.\nVitamin B\n6\n Toxicity\nThe ingestion of megadoses (> 500 mg/day) of pyridoxine (eg, taken to treat carpal tunnel syndrome or\npremenstrual syndrome although efficacy is unproved) may cause peripheral neuropathy with deficits in a\nstocking-glove distribution, including progressive sensory ataxia and severe impairment of position and\nvibration senses. Senses of touch, temperature, and pain are less affected. Motor and central nervous\nsystems are usually intact.\nDiagnosis is clinical. Treatment is to stop taking vitamin B\n6\n. Recovery is slow and, for some patients,\nincomplete.\nVitamin B\n12\nCobalamin is a general term for compounds with biologic vitamin B\n12\n activity. These compounds are\ninvolved in nucleic acid metabolism, methyl transfer, and myelin synthesis and repair. They are necessary\nfor the formation of normal RBCs.\nFood-bound vitamin B\n12\n is released in the stomach's acid environment and is bound to R protein\n(haptocorrin). Pancreatic enzymes cleave this B\n12\n complex (B\n12\n-R protein) in the small intestine. After\ncleavage, intrinsic factor, secreted by parietal cells in the gastric mucosa, binds with vitamin B\n12\n. Intrinsic\nfactor is required for absorption of vitamin B\n12\n, which takes place in the terminal ileum.\nVitamin B\n12\n in plasma is bound to transcobalamins I and II. Transcobalamin II is responsible for delivering\nvitamin B\n12\n to tissues. The liver stores large amounts of vitamin B\n12\n. Enterohepatic reabsorption helps\nretain vitamin B\n12\n. Liver vitamin B\n12\n stores can normally sustain physiologic needs for 3 to 5 yr if B\n12\nintake stops (eg, in people who become vegans) and for months to 1 yr if enterohepatic reabsorption\ncapacity is absent.\nLarge amounts of vitamin B\n12\n seem to be nontoxic but are not recommended for regular use (ie, as a\ngeneral tonic).\nVitamin B\n12\n Deficiency\nDietary vitamin B\n12\n deficiency usually results from inadequate absorption, but deficiency can\ndevelop in vegans who do not take vitamin supplements. Deficiency causes megaloblastic\nanemia, damage to the white matter of the spinal cord and brain, and peripheral neuropathy.\nDiagnosis is usually made by measuring serum vitamin B\n12\n levels. The Schilling test helps\ndetermine etiology. Treatment consists of oral or parenteral vitamin B\n12\n. Folate (folic acid)\nshould not be used instead of vitamin B\n12\n because folate may alleviate the anemia but allow\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n86"}


created_at: 2025-06-20 08:54:40
topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 34, "chroma:document": "neurologic deficits to progress.\nEtiology\nInadequate vitamin B\n12\n intake is possible in vegans but is otherwise unlikely. Breastfed babies of vegan\nmothers may develop vitamin B\n12\n deficiency by age 4 to 6 mo because their\n[\nTable 4-5.\n Causes of Vitamin B\n12\n Deficiency]\nliver stores (which are normally extensive) are limited and their rapid growth rate results in high demand.\nVitamin B\n12\n deficiency usually results from inadequate absorption (see \nTable 4-5\n and p. \n153\n), which, in\nthe elderly, most commonly results from decreased acid secretion. In such cases, crystalline vitamin B\n12\n(such as that available in vitamin supplements) can be absorbed, but food-bound vitamin B\n12\n is not\nliberated and absorbed normally. Inadequate absorption may occur in blind loop syndrome (with\novergrowth of bacteria) or fish tapeworm infestation; in these cases, bacteria or parasites use ingested\nvitamin B\n12\n so that less is available for absorption. Vitamin B\n12\n absorption may be inadequate if ileal\nabsorptive sites are destroyed by inflammatory bowel disease or are surgically removed. Less common\ncauses of inadequate vitamin B\n12\n absorption include chronic pancreatitis, gastric surgery, malabsorption\nsyndromes, AIDS, use of certain drugs (eg, antacids, metformin), repeated exposure to nitrous oxide, and\na genetic disorder causing malabsorption in the ileum (Imerslund-Graesbeck syndrome).\nPernicious anemia\n is often used synonymously with vitamin B\n12\n deficiency. However, pernicious\nanemia specifically refers to anemia resulting from vitamin B\n12\n deficiency caused by an autoimmune\nmetaplastic atrophic gastritis with loss of intrinsic factor (see p. \n133\n). Patients with classic pernicious\nanemia, most commonly younger adults, are at increased risk of stomach and other GI cancers.\nSubacute combined degeneration\n refers to degenerative changes in the nervous system due to\nvitamin B\n12\n deficiency; they affect mostly brain and spinal cord white matter. Demyelinating or axonal\nperipheral neuropathies can occur.\nSymptoms and Signs\nAnemia usually develops insidiously. It is often more severe than its symptoms indicate because its slow\nevolution allows physiologic adaptation. Occasionally, splenomegaly and hepatomegaly occur. Various GI\nsymptoms, including weight loss and poorly localized abdominal pain, may occur. Glossitis, usually\ndescribed as burning of the tongue, is uncommon.\nNeurologic symptoms develop independently from and often without hematologic abnormalities. In early\nstages, decreased position and vibratory sensation in the extremities is accompanied by mild to moderate\nweakness and hyporeflexia. In later stages, spasticity, extensor plantar responses, greater loss of position\nand vibratory sensation in the lower extremities, and ataxia emerge. These deficits may develop in a\nstocking-glove distribution. Tactile, pain, and temperature sensations are usually spared but may be\ndifficult to assess in the elderly.\nSome patients are also irritable and mildly depressed. Paranoia (megaloblastic madness), delirium,\nconfusion, spastic ataxia, and, at times, postural hypotension may occur in advanced cases. The\nconfusion may be difficult to differentiate from age-related dementias, such as Alzheimer's disease.\nDiagnosis\n\u2022 CBC and vitamin B\n12\n and folate levels\n\u2022 Sometimes methylmalonic acid levels or Schilling test\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n87"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 35, "chroma:document": "Diagnosis is based on CBC and vitamin B\n12\n and folate levels. It is important to remember that severe\nneurologic disease may occur without anemia or macrocytosis.\nCBC detects megaloblastic anemia. Tissue deficiency and macrocytic indexes may precede the\ndevelopment of anemia. A vitamin B\n12\n level < 200 pg/mL (< 145 pmol/L) indicates vitamin B\n12\n deficiency.\nThe folate level is measured because vitamin B\n12\n deficiency must be differentiated from folate deficiency\nas a cause of megaloblastic anemia; folate supplementation can mask vitamin B\n12\n deficiency and may\nalleviate megaloblastic anemia but allow the neurologic deficits to progress or even accelerate.\nWhen clinical judgment suggests vitamin B\n12\n deficiency but the vitamin B\n12\n level is low-normal (200 to\n350 pg/mL [145 to 260 pmol/L]) or hematologic indexes are normal, other tests can be done. Measuring\nserum methylmalonic acid (MMA) levels may be useful. An elevated MMA level supports vitamin B\n12\ndeficiency but may be due to renal failure. MMA levels can also be used to monitor the response to\ntreatment. MMA levels remain normal in folate deficiency; homocysteine levels may be elevated with\neither vitamin B\n12\n or folate deficiency. Less commonly, holotranscobalamin II (transcobalamin II-B\n12\ncomplex) content is measured; when holotranscobalamin II is < 40 pg/mL (< 30 pmol/L), vitamin B\n12\n is\ndeficient.\nAfter deficiency is diagnosed, additional tests may be indicated for younger adults but usually not for the\nelderly. Unless dietary vitamin B\n12\n is obviously inadequate, measurement of serum gastrin levels or\nautoantibodies to intrinsic factor may be done; sensitivity and specificity of these tests may be poor.\nSchilling test:\n The Schilling test is useful only if diagnosing intrinsic factor deficiency is important, as in\nclassic pernicious anemia. This test is not necessary for most elderly patients. The Schilling test\nmeasures absorption of free radiolabeled vitamin B\n12\n. Radiolabeled vitamin B\n12\n is given orally, followed\nin 1 to 6 h by 1000 \n\u03bc\ng (1 mg) of parenteral vitamin B\n12\n, which reduces uptake of radiolabeled vitamin\nB\n12\n by the liver. Absorbed radiolabeled vitamin B\n12\n is excreted in urine, which is collected for 24 h. The\namount excreted is measured, and the percentage of total radiolabeled vitamin B\n12\n is determined. If\nabsorption is normal, \u2265 9% of the dose given appears in the urine. Reduced urinary excretion (< 5% if\nkidney function is normal) indicates inadequate vitamin B\n12\n absorption. Improved absorption with the\nsubsequent addition of intrinsic factor to radiolabeled vitamin B\n12\n confirms the diagnosis of pernicious\nanemia. The test is often difficult to do or interpret because of incomplete urine collection or renal\ninsufficiency. In addition, because the Schilling test does not measure absorption of protein-bound vitamin\nB\n12\n, the test does not detect defective liberation of vitamin B\n12\n from foods, which is common among the\nelderly. The Schilling test repletes vitamin B\n12\n and can mask deficiency, so it should be done only after all\nother diagnostic tests and therapeutic trials.\nIf malabsorption is identified, the Schilling test can be repeated after a 2-wk trial of an oral antibiotic. If\nantibiotic therapy corrects malabsorption, the likely cause is intestinal overgrowth of bacteria (eg, blind-\nloop syndrome).\nTreatment\n\u2022 Supplemental vitamin B\n12\nVitamin B\n12\n 1000 to 2000 \n\u03bc\ng po can be given once/day to patients who do not have severe deficiency or\nneurologic symptoms or signs. A nasal gel preparation of vitamin B\n12\n is available at a higher price. Large\noral doses can be absorbed by mass action, even when intrinsic factor is absent. If the MMA level\n(sometimes used to monitor treatment) does not decrease, patients may not be taking vitamin B\n12\n. For\nmore severe deficiency, vitamin B\n12\n 1 mg IM is usually given 1 to 4 times/wk for several weeks until\nhematologic abnormalities are corrected; then it is given once/mo."}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 35, "chroma:document": "12\n. For\nmore severe deficiency, vitamin B\n12\n 1 mg IM is usually given 1 to 4 times/wk for several weeks until\nhematologic abnormalities are corrected; then it is given once/mo.\nAlthough hematologic abnormalities are usually corrected within 6 wk (reticulocyte count should improve\nwithin 1 wk), resolution of neurologic symptoms may take much longer. Neurologic symptoms that persist\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n88"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 36, "chroma:document": "for months or years become irreversible. In most elderly people with vitamin B\n12\n deficiency and dementia,\ncognition does not improve after treatment. Vitamin B\n12\n treatment must be continued for life unless the\npathophysiologic mechanism for the deficiency is corrected.\nInfants of vegan mothers should receive supplemental vitamin B\n12\n from birth.\nVitamin C\nVitamin C (ascorbic acid) plays a role in collagen, carnitine, hormone, and amino acid formation. It is\nessential for wound healing and facilitates recovery from burns. Vitamin C is also an antioxidant, supports\nimmune function, and facilitates the absorption of iron.\nVitamin C Deficiency\nIn developed countries, vitamin C deficiency can occur as part of general undernutrition, but\nsevere deficiency (causing scurvy) is uncommon. Symptoms include fatigue, depression, and\nconnective tissue defects (eg, gingivitis, petechiae, rash, internal bleeding, impaired wound\nhealing). In infants and children, bone growth may be impaired. Diagnosis is usually clinical.\nTreatment consists of oral vitamin C.\nSevere deficiency results in scurvy, a disorder characterized by hemorrhagic manifestations and abnormal\nosteoid and dentin formation.\nEtiology\nIn adults, primary deficiency is usually due to inadequate diet. The need for dietary vitamin C is increased\nby febrile illnesses, inflammatory disorders (particularly diarrheal disorders), achlorhydria, smoking,\nthyrotoxicosis, iron deficiency, cold or heat stress, surgery, burns, and protein deficiency. Heat (eg,\nsterilization of formulas, cooking) can destroy some of the vitamin C in food.\nPathophysiology\nFormation of intercellular cement substances in connective tissues, bones, and dentin is defective,\nresulting in weakened capillaries with subsequent hemorrhage and defects in bone and related\nstructures.\nBone tissue formation becomes impaired, which, in children, causes bone lesions and poor bone growth.\nFibrous tissue forms between the diaphysis and the epiphysis, and costochondral junctions enlarge.\nDensely calcified fragments of cartilage are embedded in the fibrous tissue. Subperiosteal hemorrhages,\nsometimes due to small fractures, may occur in children or adults.\nSymptoms and Signs\nIn adults, symptoms develop after weeks to months of vitamin C depletion. Lassitude, weakness,\nirritability, weight loss, and vague myalgias and arthralgias may develop early.\nLater, symptoms related to defects in connective tissues develop. Follicular hyperkeratosis, coiled hair,\nand perifollicular hemorrhages may develop. Gums may become swollen, purple, spongy, and friable; they\nbleed easily in severe deficiency. Eventually, teeth become loose and avulsed. Secondary infections may\ndevelop. Wounds heal poorly and tear easily, and spontaneous hemorrhages may occur, especially as\necchymoses in the skin of the lower limbs or as bulbar conjunctival hemorrhage.\nOther symptoms and signs include femoral neuropathy due to hemorrhage into femoral sheaths (which\nmay mimic deep venous thrombosis), lower-extremity edema, and painful bleeding or effusions within\njoints.\nDiagnosis\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n89"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 37, "chroma:document": "\u2022 Usually, skin or gingival findings and risk factors\nDiagnosis is usually made clinically in a patient who has skin or gingival signs and is at risk of vitamin C\ndeficiency. Laboratory confirmation may be available. Anemia is common. Bleeding, coagulation, and PT\nare normal.\nSkeletal x-rays can help diagnose childhood (but not adult) scurvy. Changes are most evident at the ends\nof long bones, particularly at the knee. Early changes resemble atrophy. Loss of trabeculae results in a\nground-glass appearance. The cortex thins. A line of calcified, irregular cartilage (white line of Fraenkel)\nmay be visible at the metaphysis. A zone of rarefaction or a linear fracture proximal and parallel to the\nwhite line may be visible as only a triangular defect at the bone's lateral margin but is specific. The\nepiphysis may be compressed. Healing subperiosteal hemorrhages may elevate and calcify the\nperiosteum.\nLaboratory diagnosis, which requires measuring blood ascorbic acid, is sometimes done at academic\ncenters. Levels of < 0.6 mg/dL (< 34 \n\u03bc\nmol/L) are considered marginal; levels of < 0.2 mg/dL (< 11 \n\u03bc\nmol/L)\nindicate vitamin C deficiency. Measurement of ascorbic acid levels in the WBC-platelet layer of\ncentrifuged blood is not widely available or standardized.\nIn adults, scurvy must be differentiated from arthritis, hemorrhagic disorders, gingivitis, and protein-energy\nundernutrition. Hyperkeratotic hair follicles with surrounding hyperemia or hemorrhage are almost\npathognomonic. Bleeding gums, conjunctival hemorrhages, most petechiae, and ecchymoses are\nnonspecific.\nTreatment\n\u2022 Nutritious diet with supplemental ascorbic acid\nFor scurvy in adults, ascorbic acid 100 to 500 mg po tid is given for 1 to 2 wk, until signs disappear, and\nfollowed by a nutritious diet supplying 1 to 2 times the daily recommended intake. In scurvy, therapeutic\ndoses \nof ascorbic acid restore the functions of vitamin C in a few days. The symptoms and signs usually\ndisappear over 1 to 2 wk. Chronic gingivitis with extensive subcutaneous hemorrhage persists longer.\nPrevention\nVitamin C 75 mg po once/day for women and 90 mg po once/day for men prevents deficiency. Smokers\nshould consume an additional 35 mg/day. Five servings of most fruits and vegetables (recommended\ndaily) provide > 200 mg of vitamin C.\nVitamin C Toxicity\nThe upper limit for vitamin C intake is 2000 mg/day. Up to 10 g/day of vitamin C are sometimes taken for\nunproven health benefits, such as preventing or shortening the duration of viral infections or slowing or\nreversing the progression of cancer or atherosclerosis. Such doses may acidify the urine, cause nausea\nand diarrhea, interfere with the healthy antioxidant-prooxidant balance in the body, and, in patients with\nthalassemia or hemochromatosis, promote iron overload. Intake below the upper limit does not have toxic\neffects in healthy adults.\nVitamin D\nVitamin D has 2 main forms: D\n2\n (ergocalciferol) and D\n3\n (cholecalciferol); the latter is the naturally\noccurring form and the form used for low-dose supplementation. Vitamin D\n3\n is synthesized in skin by\nexposure to direct sunlight (ultraviolet B radiation) and obtained in the diet chiefly in fish liver oils and salt\nwater fish. In some developed countries, milk and other foods are fortified with vitamin D. Human breast\nmilk is low in vitamin D, containing an average of only 10% of the amount in fortified cow's milk.\nRequirements for vitamin D increase with age because skin synthesis declines. Sunscreen use and dark\nskin pigmentation also reduce skin synthesis of vitamin D.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n90"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 38, "chroma:document": "Vitamin D is a prohormone with several active metabolites that act as hormones. Vitamin D is metabolized\nby the liver to 25(OH)D, which is then converted by the kidneys to 1,25(OH)\n2\nD (1,25-\ndihydroxycholecalciferol, calcitriol, or active vitamin D hormone). 25(OH)D, the major circulating form, has\nsome metabolic activity, but 1,25(OH)\n2\nD is the most metabolically active. The conversion to 1,25(OH)\n2\nD\nis regulated by its own concentration, parathyroid hormone (PTH), and serum concentrations of Ca and\nphosphate.\n[\nTable 4-6.\n Actions of Vitamin D and its Metabolites]\nVitamin D affects many organ systems (see \nTable 4-6\n), but mainly it increases Ca and phosphate\nabsorption from the intestine and promotes normal bone formation and mineralization. Vitamin D and\nrelated analogs may be used to treat psoriasis, hypoparathyroidism, renal osteodystrophy, and possibly\nleukemia and breast, prostate, and colon cancers; they may also be used for immunosuppression.\nVitamin D Deficiency and Dependency\nInadequate exposure to sunlight predisposes to vitamin D deficiency. Deficiency impairs bone\nmineralization, causing rickets in children and osteomalacia in adults and possibly contributing\nto osteoporosis. Treatment usually consists of oral vitamin D; Ca and phosphate are\nsupplemented as needed. Prevention is often possible. Rarely, hereditary disorders cause\nimpaired metabolism of vitamin D (dependency).\nVitamin D deficiency is a common cause of rickets and osteomalacia, but these disorders may also result\nfrom other conditions, such as various renal tubular disorders, familial hypophosphatemic (vitamin D-\nresistant) rickets (see p. \n2991\n), chronic metabolic acidosis, hypoparathyroidism (which reduces vitamin D\nabsorption), inadequate dietary Ca, and disorders or drugs that impair the mineralization of bone matrix.\nVitamin D deficiency causes hypocalcemia, which stimulates production of PTH, causing\nhyperparathyroidism. Hyperparathyroidism increases absorption, bone mobilization, and renal\nconservation of Ca but increases excretion of phosphate. As a result, the serum level of Ca may be\nnormal, but because of hypophosphatemia, bone mineralization is impaired.\nEtiology\nVitamin D deficiency may result from the following.\nInadequate exposure or intake:\n Inadequate direct sunlight exposure (or sunscreen use) and\ninadequate intake usually occur simultaneously to result in clinical deficiency. Susceptible people include\nthe elderly (who are often undernourished and are not exposed to enough sunlight), and certain\ncommunities (eg, women and children who are confined to the home or who wear clothing that covers the\nentire body and face). Inadequate vitamin D stores are common among the elderly, particularly those who\nare house-bound, institutionalized, or hospitalized or who have had a hip fracture. Recommended direct\nsunlight exposure is 5 to 15 min (suberythemal dose) to arms and legs, or face, arms and hands, at least\n3 times a week.\nReduced absorption:\n Malabsorption can deprive the body of dietary vitamin D; only a small amount of\n25(OH)D is recirculated enterohepatically.\nAbnormal metabolism:\n Vitamin D deficiency may result from defects in the production of 25(OH)D or\n1,25(OH)\n2\nD. People with a chronic renal disorder commonly develop rickets or osteomalacia because\nrenal production of 1,25 (OH)\n2\nD is decreased and phosphate levels are elevated. Hepatic dysfunction\ncan also interfere with production of active vitamin D metabolites.\nType I hereditary vitamin D-dependent rickets is an autosomal recessive disorder characterized by absent\nor defective conversion of 25(OH)D to 1,25(OH)\n2\nD in the kidneys. X-linked familial hypophosphatemia\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n91"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 39, "chroma:document": "reduces vitamin D synthesis in the kidneys. Many anticonvulsants and glucocorticoid use increase the\nneed for vitamin D supplementation.\nResistance to effects of vitamin D:\n Type II hereditary vitamin D-dependent rickets has several forms\nand is due to mutations in the 1,25(OH)\n2\nD receptor. This receptor affects the metabolism of gut, kidney,\nbone, and other cells. In this disorder, 1,25(OH)\n2\nD is abundant but ineffective because the receptor is not\nfunctional.\nSymptoms and Signs\nVitamin D deficiency can cause muscle aches, muscle weakness, and bone pain at any age.\nVitamin D deficiency in a pregnant woman causes deficiency in the fetus. Occasionally, deficiency severe\nenough to cause maternal osteomalacia results in rickets with metaphyseal lesions in neonates. In young\ninfants, rickets causes softening of the entire skull (craniotabes). When palpated, the occiput and\nposterior parietal bones feel like a ping pong ball. In older infants with rickets, sitting and crawling are\ndelayed, as is fontanelle closure; there is bossing of the skull and costochondral thickening.\nCostochondral thickening can look like beadlike prominences along the lateral chest wall (rachitic rosary).\nIn children 1 to 4 yr, epiphyseal cartilage at the lower ends of the radius, ulna, tibia, and fibula enlarges;\nkyphoscoliosis develops, and walking is delayed. In older children and adolescents, walking is painful; in\nextreme cases, deformities such as bowlegs and knock-knees develop.\nTetany is caused by hypocalcemia and may accompany infantile or adult vitamin D deficiency. Tetany may\ncause paresthesias of the lips, tongue, and fingers; carpopedal and facial spasm; and, if very severe,\nseizures. Maternal deficiency can cause tetany in neonates.\nOsteomalacia predisposes to fractures. In the elderly, hip fractures may result from only minimal trauma.\nDiagnosis\n\u2022 Levels of 25(OH)D (D\n2\n+D\n3\n)\nDiagnosis may be suspected based on any of the following:\n\u2022 A history of inadequate sunlight exposure or dietary intake\n\u2022 Symptoms and signs of rickets, osteomalacia, or neonatal tetany\n\u2022 Characteristic bone changes seen on x-ray\nX-rays of the radius and ulna plus serum levels of Ca, phosphate, alkaline phosphatase, PTH, and\n25(OH)D are needed to differentiate vitamin D deficiency from other causes of bone demineralization.\nAssessment of vitamin D status and serologic tests for syphilis can be considered for infants with\ncraniotabes based on the history and physical, but most cases of craniotabes resolve spontaneously.\nRickets can be distinguished from chondrodystrophy because the latter is characterized by a large head,\nshort extremities, thick bones, and normal serum Ca, phosphate, and alkaline phosphatase levels.\nTetany due to infantile rickets may be clinically indistinguishable from seizures due to other causes. Blood\ntests and clinical history may help distinguish them.\nBone changes, seen on x-rays, precede clinical signs. In rickets, changes are most evident at the lower\nends of the radius and ulna. The diaphyseal ends lose their sharp, clear outline; they are cup-shaped and\nshow a spotty or fringy rarefaction. Later, because the ends of the radius and ulna have become\nnoncalcified and radiolucent, the distance between them and the metacarpal bones appears increased.\nThe bone matrix elsewhere also becomes more radiolucent. Characteristic deformities result from the\nbones bending at the cartilage-shaft junction because the shaft is weak. As healing begins, a thin white\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n92"}


created_at: 2025-06-20 08:54:40
topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 40, "chroma:document": "line of calcification appears at the epiphysis, becoming denser and thicker as calcification proceeds.\nLater, the bone matrix becomes calcified and opacified at the subperiosteal level.\nIn adults, bone demineralization, particularly in the spine, pelvis, and lower extremities, can be seen on x-\nrays; the fibrous lamellae can also be seen, and incomplete ribbonlike areas of demineralization\n(pseudofractures, Looser's lines, Milkman's syndrome) appear in the cortex.\nBecause levels of serum 25(OH)D reflect body stores of vitamin D and correlate with symptoms and signs\nof vitamin D deficiency better than levels of other vitamin D metabolites, 25(OH)D (D\n2\n+D\n3\n) measurement\nis generally considered the best way to diagnose deficiency. Goal 25(OH)D levels are 30 to 40 ng/mL\n(about 75 to 100 nmol/L); whether higher levels may be beneficial remains uncertain.\nIf the diagnosis is unclear, serum levels of 1,25(OH)\n2\nD and urinary Ca concentration can be measured. In\nsevere deficiency, serum 1,25(OH)\n2\nD is abnormally low, usually undetectable. Urinary Ca is low in all\nforms of the deficiency except those associated with acidosis.\nIn vitamin D deficiency, serum Ca may be low or, because of secondary hyperparathyroidism, may be\nnormal. Serum phosphate usually decreases, and serum alkaline phosphatase usually increases. Serum\nPTH is elevated.\nType I hereditary vitamin D-dependent rickets results in normal serum 25(OH)D, low serum 1,25(OH)\n2\nD\nand Ca, and normal or low serum phosphate.\nTreatment\n\u2022 Correction of Ca and phosphate deficiencies\n\u2022 Supplemental vitamin D\nCa deficiency (which is common) and phosphate deficiency should be corrected. As long as Ca and\nphosphate intake is adequate, adults with osteomalacia and children with uncomplicated rickets can be\ncured by giving vitamin D 40 \n\u03bc\ng (1600 IU) po once/day. Serum 25(OH)D and 1,25(OH)\n2\nD begin to\nincrease within 1 or 2 days. Serum Ca and phosphate increase and serum alkaline phosphatase\ndecreases within about 10 days. During the 3rd wk, enough Ca and phosphate are deposited in bones to\nbe visible on x-rays. After about 1 mo, the dose can usually be reduced gradually to the usual\nmaintenance level of 10 to 15 \n\u03bc\ng (400 to 600 IU) once/day. If tetany is present, vitamin D should be\nsupplemented with IV Ca salts for up to 1 wk (see p. \n841\n). Elderly patients may need 25 to \u2265 50 \n\u03bc\ng (1000\nto \u2265 2000 IU) daily to maintain a 25(OH)D level > 30 ng/mL (> 75 nmol/L); this dose is higher than the\nrecommended daily allowance (RDA) for people > 70 yr (600 IU) and may exceed the current upper limit\nof 2000 IU/day.\nBecause rickets and osteomalacia due to defective production of vitamin D metabolites are vitamin D-\nresistant, they do not respond to the doses usually effective for rickets due to inadequate intake.\nEndocrinologic evaluation is required because treatment depends on the specific defect. When 25(OH)D\nproduction is defective, vitamin D 50 \n\u03bc\ng (2000 IU) once/day increases serum levels and results in clinical\nimprovement. Patients with kidney disorders often need 1,25(OH)\n2\nD supplementation.\nType I hereditary vitamin D-dependent rickets responds to 1,25(OH)\n2\nD 1 to 2 \n\u03bc\ng po once/day. Some\npatients with type II hereditary vitamin D-dependent rickets respond to very high doses (eg, 10 to 24\n\u03bc\ng/day) of 1,25(OH)\n2\nD; others require long-term infusions of Ca.\nPrevention\nDietary counseling is particularly important in communities whose members are at risk of vitamin D\ndeficiency. Fortifying unleavened chapati flour with vitamin D (125 \n\u03bc\ng/kg) has been effective among Indian\nimmigrants in Britain. The benefits of sunlight exposure for vitamin D status must be weighed against the\nincreased skin damage and skin cancer risks.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n93"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 41, "chroma:document": "increased skin damage and skin cancer risks.\nAll breastfed infants should be given supplemental vitamin D 5 \n\u03bc\ng (200 IU) once/day from birth to 6 mo; at\n6 mo, a more diversified diet is available. For adolescents at risk, a single IM dose of ergocalciferol 2.5\nmg (100,000 IU) given in the fall can maintain adequate 25(OH)D levels throughout the winter. The\nrecommended daily allowance (RDA) for vitamin D is 400 IU for people aged 51 to 70 and \n600 IU for\nthose >70; many consider this intake too low, and the 2005 Dietary Guidelines for Americans\nrecommends that healthy older adults consume 1000 IU/day.\nVitamin D Toxicity\nUsually, vitamin D toxicity results from taking excessive amounts. Marked hypercalcemia\ncommonly causes symptoms. Diagnosis is typically based on elevated blood levels of 25(OH)D.\nTreatment consists of stopping vitamin D, restricting dietary Ca, restoring intravascular volume\ndeficits, and, if toxicity is severe, giving corticosteroids or bisphosphonates.\nBecause synthesis of 1,25(OH)\n2\nD (the most active metabolite of vitamin D) is tightly regulated, vitamin D\ntoxicity usually occurs only if excessive doses (prescription or megavitamin) are taken. Vitamin D 1000 \n\u03bc\ng\n(40,000 IU)/day causes toxicity within 1 to 4 mo in infants. In adults, taking 1250 \n\u03bc\ng (50,000 IU)/day for\nseveral months can cause toxicity. Vitamin D toxicity can occur iatrogenically when hypoparathyroidism is\ntreated too aggressively (see p.\n844\n).\nSymptoms and Signs\nThe main symptoms result from hypercalcemia. Anorexia, nausea, and vomiting can develop, often\nfollowed by polyuria, polydipsia, weakness, nervousness, pruritus, and eventually renal failure.\nProteinuria, urinary casts, azotemia, and metastatic calcifications (particularly in the kidneys) can develop.\nDiagnosis\n\u2022 Hypercalcemia plus risk factors or elevated serum 25(OH)D levels\nA history of excessive vitamin D intake may be the only clue differentiating vitamin D toxicity from other\ncauses of hypercalcemia. Elevated serum Ca levels of 12 to 16 mg/dL (3 to 4 mmol/L) are a constant\nfinding when toxic symptoms occur. Serum 25(OH)D levels are usually elevated > 150 ng/mL (> 375\nnmol/L). Levels of 1,25(OH)\n2\nD, which need not be measured to confirm the diagnosis, may be normal.\nSerum Ca should be measured often (weekly at first, then monthly) in all patients receiving large doses of\nvitamin D, particularly the potent 1,25(OH)\n2\nD.\nTreatment\n\u2022 IV hydration plus corticosteroids or bisphosphonates\nAfter stopping vitamin D intake, hydration with IV normal saline and corticosteroids or bisphosphonates\n(which inhibit bone resorption) are used to reduce blood Ca levels.\nKidney damage or metastatic calcifications, if present, may be irreversible.\nVitamin E\nVitamin E is a group of compounds (including tocopherols and tocotrienols) that have similar biologic\nactivities. The most biologically active is \n\u03b1\n-tocopherol, but \n\u03b2\n-, \n\u03b3\n-, and \n\u03b4\n-tocopherols, 4 tocotrienols, and\nseveral stereoisomers may also have important biologic activity. These compounds act as antioxidants,\nwhich prevent lipid peroxidation of polyunsaturated fatty acids in cellular membranes. Plasma tocopherol\nlevels vary with total plasma lipid levels. Normally, the plasma \n\u03b1\n-tocopherol level is 5 to 20 \n\u03bc\ng/mL (11.6 to\n46.4 \n\u03bc\nmol/L). High-dose vitamin E supplements do not protect against cardiovascular disorders;whether\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n94"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 42, "chroma:document": "supplements can protect against Alzheimer's disease, tardive dyskinesia, and prostate cancer among\nsmokers is controversial.\nAlthough the amount of vitamin E in many fortified foods and supplements is given in IU, current\nrecommendations are to use mg.\nVitamin E Deficiency\nDietary vitamin E deficiency is common in developing countries; deficiency among adults in\ndeveloped countries is uncommon and usually due to fat malabsorption. The main symptoms\nare hemolytic anemia and neurologic deficits. Diagnosis is based on measuring the ratio of\nplasma \n\u03b1\n-tocopherol to total plasma lipids; a low ratio suggests vitamin E deficiency. Treatment\nconsists of oral vitamin E, given in high doses if there are neurologic deficits or if deficiency\nresults from malabsorption.\nVitamin E deficiency causes fragility of RBCs and degeneration of neurons, particularly peripheral axons\nand posterior column neurons.\nEtiology\nIn developing countries, the most common cause is inadequate intake of vitamin E. In developed\ncountries, the most common causes are disorders that cause fat malabsorption, including\nabetalipoproteinemia (Bassen-Kornzweig syndrome, due to genetic absence of apolipoprotein B), chronic\ncholestatic \nhepatobiliary disease, pancreatitis, short bowel syndrome, and cystic fibrosis. A rare genetic\nform of vitamin E deficiency without fat malabsorption results from defective liver metabolism.\nSymptoms and Signs\nThe main symptoms are mild hemolytic anemia and nonspecific neurologic deficits. Abetalipoproteinemia\nresults in progressive neuropathy and retinopathy in the first 2 decades of life (see p. \n904\n).\nVitamin E deficiency may contribute to retinopathy of prematurity (also called retrolental fibroplasia) in\npremature infants and to some cases of intraventricular and subependymal hemorrhage in neonates.\nAffected premature neonates have muscle weakness.\nIn children, chronic cholestatic hepatobiliary disease or cystic fibrosis causes neurologic deficits, including\nspinocerebellar ataxia with loss of deep tendon reflexes, truncal and limb ataxia, loss of vibration and\nposition senses, ophthalmoplegia, muscle weakness, ptosis, and dysarthria.\nIn adults with malabsorption, vitamin E deficiency very rarely causes spinocerebellar ataxia because\nadults have large vitamin E stores in adipose tissue.\nDiagnosis\n\u2022 Low \n\u03b1\n-tocopherol level or low ratio of serum \n\u03b1\n-tocopherol to serum lipids\nWithout a history of inadequate intake or a predisposing condition, vitamin E deficiency is unlikely.\nConfirmation usually requires measuring the vitamin level. Measuring RBC hemolysis in response to\nperoxide can suggest the diagnosis but is nonspecific. Hemolysis increases as vitamin E deficiency\nimpairs RBC stability.\nMeasuring the serum \n\u03b1\n-tocopherol level is the most direct method of diagnosis. In adults, vitamin E\ndeficiency is suggested if the \n\u03b1\n-tocopherol level is < 5 \n\u03bc\ng/mL (< 11.6 \n\u03bc\nmol/L). Because abnormal lipid\nlevels can affect vitamin E status, a low ratio of serum \n\u03b1\n-tocopherol to lipids (< 0.8 mg/g total lipid) is the\nmost accurate indicator in adults with hyperlipidemia.\nIn children and adults with abetalipoproteinemia, serum \n\u03b1\n-tocopherol levels are usually undetectable.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n95"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 43, "chroma:document": "Treatment\n\u2022 Supplemental \n\u03b1\n-tocopherol\nIf malabsorption causes clinically evident deficiency, \n\u03b1\n-tocopherol 15 to 25 mg/kg po once/day should be\ngiven. However, larger doses given by injection are required to treat neuropathy during its early stages or\nto overcome the defect of absorption and transport in abetalipoproteinemia.\nPrevention\nAlthough premature neonates may require supplementation, human milk and commercial formulas have\nenough vitamin E for full-term neonates.\nVitamin E Toxicity\nMany adults take relatively large amounts of vitamin E (\n\u03b1\n-tocopherol 400 to 800 mg/day) for months to\nyears without any apparent harm. Occasionally, muscle weakness, fatigue, nausea, and diarrhea occur.\nThe most significant risk is bleeding. However, bleeding is uncommon unless the dose is > 1000 mg/day\nor the patient takes oral coumarin or warfarin. Thus, the upper limit for adults aged \u226519 yr is 1000 mg for\nany form of \n\u03b1\n-tocopherol. Recent analyses of previous studies report that high vitamin E intakes may\nincrease the risk of hemorrhagic stroke and premature death.\nVitamin K\nVitamin K\n1\n (phylloquinone) is dietary vitamin K. Dietary fat enhances its absorption. Infant formulas\ncontain supplemental vitamin K. Vitamin K\n2\n refers to a group of compounds (menaquinones) synthesized\nby bacteria in the intestinal tract; the amount synthesized does not satisfy the vitamin K requirement.\nVitamin K controls the formation of coagulation factors II (prothrombin), VII, IX, and X in the liver. Other\ncoagulation factors dependent on vitamin K are protein C, protein S, and protein Z; proteins C and S are\nanticoagulants. Metabolic pathways conserve vitamin K. Once vitamin K has participated in formation of\ncoagulation factors, the reaction product, vitamin K epoxide, is enzymatically converted to the active form,\nvitamin K hydroquinone.\nThe actions of vitamin K-dependent proteins require Ca. The vitamin K-dependent proteins, osteocalcin\nand matrix \n\u03b3\n-carboxy-glutamyl (Gla) protein, may have important roles in bone and other tissues. Forms of\nvitamin K are common therapy for osteoporosis in Japan and other countries.\nVitamin K Deficiency\nVitamin K deficiency results from extremely inadequate intake, fat malabsorption, or use of\ncoumarin anticoagulants. Deficiency is particularly common among breastfed infants. It impairs\nclotting. Diagnosis is suspected based on routine coagulation study findings and confirmed by\nresponse to vitamin K. Treatment consists of vitamin K given orally or, when fat malabsorption\nis the cause or risk of bleeding is high, parenterally.\nVitamin K deficiency decreases levels of prothrombin and other vitamin K-dependent coagulation factors,\ncausing defective coagulation and, potentially, bleeding.\nEtiology\nWorldwide, vitamin K deficiency causes infant morbidity and mortality. Vitamin K deficiency causes\nhemorrhagic disease of the newborn, which usually occurs 1 to 7 days postpartum. In affected neonates,\nbirth trauma can cause intracranial hemorrhage. Neonates are prone to vitamin K deficiency because of\nthe following:\n\u2022 The placenta transmits lipids and vitamin K relatively poorly.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n96"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 44, "chroma:document": "\u2022 The neonatal liver is immature with respect to prothrombin synthesis.\n\u2022 Breast milk is low in vitamin K, containing about 2.5 \n\u03bc\ng/L (cow's milk contains 5000 \n\u03bc\ng/L).\n\u2022 The neonatal gut is sterile during the first few days of life.\nLate hemorrhagic disease (occurring 3 to 8 wk postpartum) is usually associated with breastfeeding,\nmalabsorption, or a liver disorder. If the mother has taken phenytoin anticonvulsants, coumarin\nanticoagulants, or cephalosporin antibiotics, the risk of both types of hemorrhagic disease is increased.\nIn healthy adults, dietary vitamin K deficiency is uncommon because vitamin K is widely distributed in\ngreen vegetables and the bacteria of the normal gut synthesize menaquinones. However, biliary\nobstruction, malabsorption, cystic fibrosis, and resection of the small intestine can contribute to vitamin K\ndeficiency.\nCoumarin anticoagulants interfere with the synthesis of vitamin K-dependent coagulation proteins (factors\nII, VII, IX, and X) in the liver. Certain antibiotics (particularly some cephalosporins and other broad-\nspectrum antibiotics), salicylates, megadoses of vitamin E, and hepatic insufficiency increase risk of\nbleeding in patients with vitamin K deficiency.\nSymptoms and Signs\nBleeding is the usual manifestation. Easy bruisability and mucosal bleeding (especially epistaxis, GI\nhemorrhage, menorrhagia, and hematuria) can occur. Blood may ooze from puncture sites or incisions.\nHemorrhagic disease of the newborn and late hemorrhagic disease in infants may cause cutaneous, GI,\nintrathoracic, or, in the worst cases, intracranial bleeding. If obstructive jaundice develops, bleeding\u2014if it\noccurs\u2014usually begins after the 4th or 5th day. It may begin as a slow ooze from a surgical incision, the\ngums, the nose, or GI mucosa, or it may begin as massive bleeding into the GI tract.\nDiagnosis\n\u2022 Usually, prolonged PT that decreases after phytonadione\nVitamin K deficiency or antagonism (due to coumarin anticoagulants) is suspected when abnormal\nbleeding occurs in a patient at risk. Blood coagulation studies can preliminarily confirm the diagnosis. PT,\nusually reported as the INR, is prolonged, but PTT, thrombin time, platelet count, bleeding time, and\nlevels of fibrinogen, fibrin-split products, and D-dimer are normal. If phytonadione (USP generic name for\nvitamin K\n1\n) 1 mg IV significantly decreases PT within 2 to 6 h, a liver disorder is not the likely cause, and\nthe diagnosis of vitamin K deficiency is confirmed. Some centers can detect vitamin K deficiency more\ndirectly by measuring the serum vitamin level. The serum level of vitamin K\n1\n ranges from 0.2 to 1.0 ng/mL\nin healthy people consuming adequate quantities of vitamin K\n1\n (50 to 150 \n\u03bc\ng/day). Knowing vitamin K\nintake can help interpret serum levels; recent intake affects levels in serum but not in tissues.\nMore sensitive indicators of vitamin K status, such as PIVKA (\nP\nrotein \nI\nnduced in \nV\nitamin \nK A\nbsence or\nA\nntagonism) and under-carboxylated osteocalcin, are under study.\nTreatment\n\u2022 Phytonadione\nWhenever possible, phytonadione should be given po or sc. The usual adult dose is 5 to 20 mg. (Rarely,\neven when phytonadione is correctly diluted and given slowly, IV replacement can result in anaphylaxis or\nanaphylactoid reactions.) INR usually decreases within 6 to 12 h. The dose may be repeated in 6 to 8 h if\nINR has not decreased satisfactorily. Phytonadione 2.5 to 10 mg po is indicated for \nnonemergency\ncorrection of a prolonged INR in patients taking anticoagulants. Correction usually occurs within 6 to 8 h.\nWhen only partial correction of INR is desirable (eg, when INR should remain slightly elevated because of\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n97"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 45, "chroma:document": "a prosthetic heart valve), lower doses (eg, 1 to 2.5 mg) of phytonadione can be given.\nIn infants, bleeding due to deficiency can be corrected by giving phytonadione 1 mg sc or IM once. The\ndose is repeated if INR remains elevated. Higher doses may be necessary if the mother has been taking\noral anticoagulants.\nPrevention\nPhytonadione 0.5 to 1 mg IM (or 0.3 mg/kg for preterm infants) is recommended for all neonates within 6 h\nof birth to reduce the incidence of intracranial hemorrhage due to birth trauma and of classic hemorrhagic\ndisease of the newborn (increased bleeding risks 1 to 7 days after birth). It is also used prophylactically\nbefore surgery. Some clinicians recommend that pregnant women taking anticonvulsants receive\nphytonadione 10 mg po once/day for the 1 mo or 20 mg po once/day for the 2 wk before delivery. The low\nvitamin K\n1\n content in breast milk can be increased by increasing maternal dietary intake of phylloquinone\nto 5 mg/day.\nVitamin K Toxicity\nVitamin K\n1\n (phylloquinone) is not toxic when consumed orally, even in large amounts. However,\nmenadione (a synthetic, water-soluble vitamin K precursor) can cause toxicity and should not be used to\ntreat vitamin K deficiency.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 4. Vitamin Deficiency, Dependency & Toxicity\n98"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 46, "chroma:document": "Chapter 5. Mineral Deficiency and Toxicity\nIntroduction\nSix macrominerals are required by people in gram amounts. Four (Na, K, Ca, and Mg) are cations; two (Cl\nand P) are accompanying anions (see p. \n820\n). Daily requirements range from 0.3 to 2.0 g. Bone, muscle,\nheart, and brain function depend on these minerals.\nNine trace minerals (microminerals) are required by people in minute amounts: chromium, copper, iodine,\niron, fluorine, manganese, molybdenum, selenium, and zinc. (For sources, functions, effects of deficiency\nand toxicity, and dietary requirements, see\nTables 5-1\n and\n5-2\n.) All trace minerals are toxic at high levels; some minerals (arsenic, nickel, and chromium) may be\ncarcinogens.\nMineral deficiencies (except of iodine, iron, and zinc) do not often develop spontaneously in adults on\nordinary diets; infants are more vulnerable because their growth is rapid and intake varies. Trace mineral\nimbalances can result from hereditary disorders (eg, hemochromatosis, Wilson's disease), kidney dialysis,\nparenteral nutrition, or restrictive diets prescribed for people with inborn errors of metabolism.\nChromium\nOnly 1 to 3% of biologically active trivalent chromium (Cr) is absorbed. Normal plasma levels are 0.05 to\n0.50 \n\u03bc\ng/L (1.0 to 9.6 nmol/L). Chromium potentiates insulin activity and increases the growth rate in\nundernourished children. Supplements do not enhance muscle size or strength in men.\nDeficiency:\n Four patients receiving long-term TPN developed possible chromium deficiency, with\nglucose intolerance, weight loss, ataxia, and peripheral neuropathy. Symptoms resolved in 3 who were\ngiven trivalent chromium 150 to 250 mg.\nToxicity:\n High doses of trivalent chromium given parenterally cause skin irritation, but lower doses given\norally are not toxic. Exposure to hexavalent chromium (CrO\n3\n) in the workplace may irritate the skin, lungs,\nand GI tract and may cause perforation of the nasal septum and lung carcinoma.\nCopper\nCopper is a component of many body proteins; almost all of the body's copper is bound to copper\nproteins. Unbound (free) copper ions are toxic. Genetic mechanisms control the incorporation of copper\ninto apoproteins and the processes that prevent toxic accumulation of copper in the body. Copper\nabsorbed in excess of metabolic requirements is excreted through bile.\n[\nTable 5-1.\n Trace Minerals]\nAcquired Copper Deficiency\nIf the genetic mechanisms controlling copper metabolism are normal, dietary deficiency rarely causes\nclinically significant copper deficiency. The only reported causes are kwashiorkor, persistent infantile\ndiarrhea (usually associated with a diet limited to milk), severe malabsorption (as in sprue), and excessive\nzinc intake.\nDeficiency may cause neutropenia, impaired bone calcification, and hypochromic anemia not responsive\nto iron supplements.\nDiagnosis is based on low serum levels of copper and ceruloplasmin, although these tests are not always\nreliable. Treatment is directed at the cause, and copper 1.5 to 3 mg/day po (usually as copper sulfate) is\ngiven.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5. Mineral Deficiency & Toxicity\n99"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 47, "chroma:document": "Inherited Copper Deficiency\n(Menkes Syndrome)\nInherited copper deficiency occurs in male infants who inherit a mutant X-linked gene. Incidence is about\n1 in 50,000 live births. Copper is deficient in the liver, serum, and essential copper proteins, including\ncytochrome-c oxidase, ceruloplasmin, and lysyl oxidase.\nSymptoms are severe intellectual disability, vomiting, diarrhea, protein-losing enteropathy,\nhypopigmentation, bone changes, and arterial rupture; the hair is sparse, steely, or kinky.\nDiagnosis\n\u2022 Serum copper and ceruloplasmin levels\n\u2022 Serum levels of dopamine, norepinephrine, dihydroxyphenylacetic acid, and dihydroxyphenylglycol in\ninfants at risk\nDiagnosis is based on low copper and ceruloplasmin levels in serum, although these tests are not always\nreliable. Because early diagnosis and treatment seem to result in a better prognosis, the disorder is\nideally detected before age 2 wk. However, diagnostic accuracy of these tests is limited. Thus, infants at\nrisk (eg, those with a family history) can be screened by measuring dopamine, norepinephrine,\ndihydroxyphenylacetic acid, and dihydroxyphenylglycol in serum. A dihydroxyphenylacetic\nacid:dihydroxyphenylglycol ratio of > 4 seems to indicate deficiency, and a dopamine:norepinephrine ratio\nof > 0.2 seems to confirm it.\nTreatment\n\u2022 Copper histidine\nParenteral copper is usually given as copper histidine 250 \n\u03bc\ng sc bid to age 1 yr, then 250 \n\u03bc\ng sc once/day\nuntil age 3 yr; monitoring kidney function is essential during treatment. Despite early treatment, many\nchildren have abnormal neurodevelopment.\nAcquired Copper Toxicity\nAcquired copper toxicity can result from ingesting or absorbing excess copper (eg, from ingesting an\nacidic food or beverage that has had prolonged contact with a copper container). Self-limited\ngastroenteritis with nausea, vomiting, and diarrhea may occur.\n[\nTable 5-2.\n Guidelines for Daily Intake of Minerals]\nMore severe toxicity results from ingestion (usually with suicidal intent) of gram quantities of a copper salt\n(eg, copper sulfate) or from absorption of large amounts through the skin (eg, if compresses saturated\nwith a solution of a copper salt are applied to large areas of burned skin). Hemolytic anemia and anuria\ncan result and may be fatal.\nIndian childhood cirrhosis, non-Indian childhood cirrhosis, and idiopathic copper toxicity are probably\nidentical disorders in which excess copper causes cirrhosis. All seem to be caused by ingesting milk that\nhas been boiled or stored in corroded copper or brass vessels. Recent studies suggest that idiopathic\ncopper toxicity may develop only in infants with an unknown genetic defect.\nDiagnosis usually requires liver biopsy, which shows Mallory hyalin bodies.\nTreatment\n\u2022 Chelation\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5. Mineral Deficiency & Toxicity\n100"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 48, "chroma:document": "\u2022 Supportive measures\nFor copper toxicity due to ingesting grams of copper, prompt gastric lavage is done. Copper toxicity that\ncauses complications such as hemolytic anemia, anuria, or hepatotoxicity is also treated with either oral\npenicillamine 250 mg q 6 h to 750 mg q 12 h (1000 to 1500 mg/day in 2 to 4 doses) or dimercaprol 3 to 5\nmg/kg IM q 4 h for 2 days, then q 4 to 6 h (see also\nTable 340-4\n and copper salts in\nTable 340-8\n). If used early, hemodialysis may be effective. Occasionally, copper toxicity is fatal despite\ntreatment.\nInherited Copper Toxicity\n(Wilson's Disease)\nInherited copper toxicity results in accumulation of copper in the liver and other organs. Hepatic\nor neurologic symptoms develop. Diagnosis is based on a low serum ceruloplasmin level, high\nurinary excretion of copper, and sometimes liver biopsy results. Treatment consists of a low-\ncopper diet and chelation, usually with penicillamine or dimercaprol.\nWilson's disease is a progressive disorder of copper metabolism that affects 1 person in 30,000. Affected\npeople are homozygous for the mutant recessive gene, located on chromosome 13. Heterozygous\ncarriers, who constitute about 1.1% of the population, are asymptomatic.\nPathophysiology\nThe genetic defect impairs copper transport. The impaired transport decreases copper secretion into the\nbile, thus causing the copper overload and resultant accumulation in the liver, which begins at birth. The\nimpaired transport also interferes with incorporation of copper into the copper protein ceruloplasmin, thus\ndecreasing serum levels of ceruloplasmin.\nHepatic fibrosis develops, ultimately causing cirrhosis. Copper diffuses out of the liver into the blood, then\ninto other tissues. It is most destructive to the brain but also damages the kidneys and reproductive\norgans and causes hemolytic anemia. Some copper is deposited in Descemet's membrane of the cornea,\ncausing Kayser-Fleischer rings.\nSymptoms and Signs\nSymptoms usually develop between ages 5 and 40. In almost half of patients, particularly adolescents,\nthe first symptom is hepatitis\u2014acute, chronic active, or fulminant. But hepatitis may develop at any time.\nIn about 40% of patients, particularly young adults, the first symptoms reflect CNS involvement. Motor\ndeficits are common, including any combination of tremors, dystonia, dysarthria, dysphagia, chorea,\ndrooling, and incoordination. Sometimes the first symptoms are cognitive or psychiatric abnormalities. In 5\nto 10% of patients, the first symptom is incidentally noted gold or greenish gold Kayser-Fleischer rings or\ncrescents (due to copper deposits in the cornea), amenorrhea or repeated miscarriages, or hematuria.\nDiagnosis\n\u2022 Slit-lamp examination for Kayser-Fleischer rings\n\u2022 Serum ceruloplasmin and 24-h urinary copper excretion\n\u2022 Sometimes confirmation by penicillamine provocation test or liver biopsy\nWilson's disease should be suspected in people < 40 with any of the following:\n\u2022 An unexplained hepatic, neurologic, or psychiatric disorder\n\u2022 An unexplained persistent elevation in hepatic transaminases\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5. Mineral Deficiency & Toxicity\n101"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 49, "chroma:document": "\u2022 A sibling, parent, or cousin with Wilson's disease\n\u2022 Fulminant hepatitis\nIf Wilson's disease is suspected, slit-lamp examination for Kayser-Fleischer rings is required, and serum\nceruloplasmin and copper levels and 24-h urinary copper excretion are measured. Transaminase levels\nare also often measured; high levels are consistent with the diagnosis.\nKayser-Fleischer rings:\n These rings plus typical motor neurologic abnormalities or a decrease in\nceruloplasmin are nearly pathognomonic for Wilson's disease. Rarely, these rings occur in other liver\ndisorders (eg, biliary atresia, primary biliary cirrhosis), but ceruloplasmin levels should be unaffected.\nCeruloplasmin:\n Serum ceruloplasmin (normally 20 to 35 mg/dL) is usually low in Wilson's disease but\ncan be normal. It can also be low in heterozygous carriers and those with other liver disorders (eg, viral\nhepatitis, drug- or alcohol-induced liver disease). A low ceruloplasmin level in a patient with a \nKayser-\nFleischer ring is diagnostic. Also, a level of < 5 mg/dL is highly suggestive regardless of clinical findings.\nSerum copper:\n Despite the copper accumulation in the body, serum copper levels are decreased\nbecause of the decreased ceruloplasmin levels.\nUrinary copper excretion:\n In Wilson's disease, 24-h urinary copper excretion (normally, \u2264 30 \n\u03bc\ng/day) is\nusually > 100 \n\u03bc\ng/day. If serum ceruloplasmin is low and urinary copper excretion is high, diagnosis is\nclear. If levels are equivocal, measuring urinary copper excretion after penicillamine is given\n(penicillamine provocation test) may confirm the diagnosis; this test is not usually done in adults because\ncutoff values are not well-established.\nLiver biopsy:\n In unclear cases (eg, elevated transaminases, no Kayser-Fleischer rings, indeterminate\nvalues for ceruloplasmin and urinary copper), the diagnosis is made by doing a liver biopsy to measure\nhepatic copper concentration. However, false-negative results may occur because of a sampling error\n(due to large variations in copper concentrations in the liver) or fulminant hepatitis (causing necrosis that\nreleases large amounts of copper).\nScreening:\n Because early treatment is most effective, screening is indicated for anyone who has a\nsibling, cousin, or parent with Wilson's disease. Screening consists of a slit-lamp examination and\nmeasurement of transaminase levels, serum copper and ceruloplasmin, and 24-h urine copper excretion.\nIf any results are abnormal, liver biopsy is done to measure hepatic copper concentration. Infants should\nnot be tested until after age 1 yr because ceruloplasmin levels are low during the first few months of life.\nChildren < 6 yr with normal test results should be retested 5 to 10 yr later.\nGenetic testing is under investigation.\nPrognosis\nPrognosis is usually good, unless disease is advanced before treatment begins. Untreated Wilson's\ndisease is fatal, usually by age 30.\nTreatment\n\u2022 Penicillamine or another chelating drug if needed to remove accumulated copper\n\u2022 Low-copper diet\n\u2022 For maintenance, lifelong low-dose chelation therapy or oral zinc\nContinual, lifelong treatment is mandatory regardless of whether symptoms are present. Accumulated\ncopper should be removed with chelating drugs. A low-copper diet (eg, avoiding beef liver, cashews,\nblack-eyed peas, vegetable juice, shellfish, mushrooms, and cocoa) and use of either low-dose chelation\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5. Mineral Deficiency & Toxicity\n102"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 50, "chroma:document": "therapy or oral zinc can prevent copper from accumulating.\nPenicillamine is the most commonly used chelating drug but has considerable toxicity (eg, fever, rash,\nneutropenia, thrombocytopenia, proteinuria). Cross-reactivity may occur in people with penicillin allergy.\nPatients > 5 yr are given oral doses of 62.5 mg q 6 h to 250 mg q 12 h (250 to 500 mg/day in 2 to 4\ndoses) and slowly increased to a maximum of 250 mg q 6 h to 750 mg q 12 h (1000 to 1500 mg/day in 2\nto 4 doses). Younger children are given 10 mg/kg bid or 6.7 mg/kg tid (20 mg/kg/d) po. Pyridoxine 25 mg\npo once/day is given with penicillamine. Occasionally, use of penicillamine is associated with worsening\nneurologic symptoms.\nTrientine hydrochloride is an alternative treatment to penicillamine. Doses are 375 to 750 mg po bid or\n250 to 500 mg po tid (750 to 1500 mg/day).\nZinc acetate 50 mg po tid can prevent reaccumulation of copper in patients who cannot tolerate\npenicillamine or trientine or who have neurologic symptoms that do not respond to the other drugs.\n(CAUTION: \nPenicillamine or trientine must not be given with zinc because either drug can bind zinc,\nforming a compound with no therapeutic effect\n.)\nPoor long-term adherence to drug therapy is common. After 1 to 5 yr of therapy, lower dose maintenance\ndrug therapy can be considered. Regular follow-up care with an expert in liver disease is recommended.\nLiver transplantation may be lifesaving for patients who have Wilson's disease and fulminant hepatic\nfailure or severe hepatic insufficiency refractory to drugs.\nFluorine\nMost of the body's fluorine (F) is contained in bones and teeth. Fluoride (the ionic form of fluorine) is\nwidely distributed in nature. The main source of fluoride is fluoridated drinking water.\nDeficiency:\n Fluorine deficiency can lead to dental caries and possibly osteoporosis. Fluoridation of\nwater that contains < 1 ppm (the ideal) reduces the incidence of dental caries. If a child's drinking water is\nnot fluoridated, oral fluoride supplements can be prescribed.\nToxicity:\n Excess fluorine can accumulate in teeth and bones, causing fluorosis. Drinking water\ncontaining > 10 ppm is a common cause. Permanent teeth that develop during \nhigh fluoride intake are\nmost likely to be affected. Exposure must be much greater to affect deciduous teeth.\nThe earliest signs are chalky white, irregularly distributed patches on the surface of the enamel; these\npatches become stained yellow or brown, producing a characteristic mottled appearance. Severe toxicity\nweakens the enamel, pitting its surface. Bony changes, including osteosclerosis, exostoses of the spine,\nand genu valgum, can develop but only in adults after prolonged high intake of fluoride.\nNo tests to diagnose toxicity are available.\nTreatment involves reducing fluoride intake; eg, in areas with high fluoride water levels, patients should\nnot drink fluoridated water or take fluoride supplements. Children should always be told not to swallow\nfluoridated toothpastes.\nIodine\nIn the body, iodine (I) is involved primarily in the synthesis of 2 thyroid hormones, thyroxine (T\n4\n) and\ntriiodothyronine (T\n3\n). Iodine occurs in the environment and in the diet primarily as iodide. In adults, about\n80% of the iodide absorbed is trapped by the thyroid gland. Most environmental iodine occurs in\nseawater as iodide; a small amount enters the atmosphere and, through rain, enters ground water and\nsoil near the sea. Thus, people living far from the sea and at higher altitudes are at particular risk of\ndeficiency. Fortifying table salt with iodide (typically 70 \n\u03bc\ng/g) helps ensure adequate intake (150 \n\u03bc\ng/day).\nRequirements are higher for pregnant (220 \n\u03bc\ng/day) and breastfeeding (290 \n\u03bc\ng/day) women.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5. Mineral Deficiency & Toxicity\n103"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 51, "chroma:document": "Iodine Deficiency\nDeficiency is rare in areas where iodized salt is used but common worldwide. Iodine deficiency develops\nwhen iodide intake is < 20 \n\u03bc\ng/day. In mild or moderate deficiency, the thyroid gland, influenced by thyroid-\nstimulating hormone (TSH), hypertrophies to concentrate iodide in itself, resulting in colloid goiter.\nUsually, patients remain euthyroid; however, severe iodine deficiency in adults may cause hypothyroidism\n(endemic myxedema). It can decrease fertility and increase risk of stillbirth, spontaneous abortion, and\nprenatal and infant mortality. Severe maternal iodine deficiency retards fetal growth and brain\ndevelopment, sometimes resulting in birth defects, and, in infants, causes cretinism, which may include\nintellectual disability, deaf-mutism, difficulty walking, short stature, and sometimes hypothyroidism.\nDiagnosis\n\u2022 Assessment of thyroid structure and function\nDiagnosis in adults and children is usually based on thyroid function, examination for goiter, and imaging\ntests identifying abnormalities in thyroid function and structure (see p.\n776\n). All neonates should be screened by measuring the TSH level.\nTreatment\n\u2022 Iodide with or without levothyroxine\nInfants with iodine deficiency are given L-thyroxine 3 \n\u03bc\ng/kg po once/day for a week plus iodide 50 to 90\n\u03bc\ng po once/day for several weeks to quickly restore a euthyroid state. Children are treated with iodide 90\nto 120 \n\u03bc\ng once/day. Adults are given iodide 150 \n\u03bc\ng once/day. Iodine deficiency can also be treated by\ngiving levothyroxine. Serum TSH levels are monitored in all patients until the levels are normal (ie, < 5\n\u03bc\nIU/mL).\nIodine Toxicity\nChronic toxicity may develop when intake is > 1.1 mg/day. Most people who ingest excess amounts of\niodine remain euthyroid. Some people who ingest excess amounts of iodine, particularly those who were\npreviously deficient, develop hyperthyroidism (Jod-Basedow phenomenon). Paradoxically, excess uptake\nof iodine by the thyroid may inhibit thyroid hormone synthesis (called Wolff-Chaikoff effect). Thus, iodine\ntoxicity can eventually cause iodide goiter, hypothyroidism, or myxedema. Very large amounts of iodide\nmay cause a brassy taste in the mouth, increased salivation, GI irritation, and acneiform skin lesions.\nPatients exposed to frequent large amounts of radiographic contrast dyes or the drug amiodarone also\nneed to have their thyroid function monitored.\nDiagnosis is usually based on thyroid function and imaging test findings (see p. \n776\n), which are\ncorrelated with clinical data. Iodine excretion may be more specific but is not usually measured. Treatment\nconsists of correcting thyroid abnormalities and, if intake is excessive, dietary modification.\nIron\nIron (Fe) is a component of hemoglobin, myoglobin, and many enzymes in the body. \nHeme iron, contained\nmainly in animal products, is absorbed much better than nonheme iron (eg, in plants and grains), which\naccounts for > 85% of iron in the average diet. However, absorption of nonheme iron is increased when it\nis consumed with animal protein and vitamin C.\nDeficiency:\n Iron deficiency is one of the most common mineral deficiencies in the world. It may result\nfrom the following:\n\u2022 Inadequate iron intake, common in infants, adolescent girls, and pregnant women\n\u2022 Malabsorption (eg, celiac sprue)\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5. Mineral Deficiency & Toxicity\n104"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 52, "chroma:document": "\u2022 Chronic bleeding\nChronic bleeding due to colon cancer is a serious cause in middle-aged people and the elderly.\nWhen deficiency is advanced, microcytic anemia develops (see p. \n924\n).\nIn addition to anemia, iron deficiency may cause pica (a craving for nonfoods) and spoon nails and is\nassociated with restless leg syndrome. Rarely, iron deficiency causes dysphagia due to postcricoid\nesophageal web.\nDiagnosis involves CBC, serum ferritin, and possibly measurement of transferrin saturation (iron\ncapacity).\nAll people with moderate or severe iron deficiency and some people with mild deficiency require iron\nsupplementation.\nToxicity:\n Iron may accumulate in the body because of\n\u2022 Iron therapy given in excessive amounts or for too long\n\u2022 Repeated blood transfusions\n\u2022 Chronic alcoholism\n\u2022 Overdose of iron\nIron overload can also result from an inherited iron overload disease (hemochromatosis\u2014see p. \n1032\n), a\npotentially fatal but easily treatable genetic disorder in which too much iron is absorbed.\nHemochromatosis affects > 1 million Americans.\nAn overdose of iron is toxic (see p. \n3341\n), causing vomiting, diarrhea, and damage to the intestine and\nother organs.\nDiagnosis is similar to that for iron deficiency.\nTreatment often involves deferoxamine, which binds with iron and is excreted in urine.\nManganese\nManganese (Mn), necessary for healthy bone structure, is a component of several enzyme systems,\nincluding manganese-specific glycosyltransferases and phosphoenolpyruvate carboxykinase. Median\nintake is between 1.6 and 2.3 mg/day; absorption is 5 to 10%.\nDeficiency has not been conclusively documented, although one experimental case in a volunteer\nresulted in transient dermatitis, hypocholesterolemia, and increased alkaline phosphatase levels.\nToxicity is usually limited to people who mine and refine ore; prolonged exposure causes neurologic\nsymptoms resembling those of parkinsonism or Wilson's disease.\nMolybdenum\nMolybdenum (Mo) is a component of coenzymes necessary for the activity of xanthine oxidase, sulfite\noxidase, and aldehyde oxidase.\nGenetic and nutritional deficiencies of molybdenum have been reported but are rare. Genetic sulfite\noxidase deficiency was described in 1967 in a child. It resulted from the inability to form the molybdenum\ncoenzyme despite the presence of adequate molybdenum. The deficiency caused intellectual disability,\nseizures, opisthotonus, and lens dislocation.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5. Mineral Deficiency & Toxicity\n105"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 53, "chroma:document": "Molybdenum deficiency resulting in sulfite toxicity occurred in a patient receiving long-term TPN.\nSymptoms were tachycardia, tachypnea, headache, nausea, vomiting, and coma. Laboratory tests\nshowed high levels of sulfite and xanthine and low levels of sulfate and uric acid in the blood and urine.\nAmmonium molybdate 300 \n\u03bc\ng/day IV caused dramatic recovery.\nA case of molybdenum toxicity may have occurred in 1961; it caused goutlike symptoms and\nabnormalities of the GI tract, liver, and kidneys.\nSelenium\nSelenium (Se) is a part of the enzyme glutathione peroxidase, which metabolizes hydro-peroxides formed\nfrom polyunsaturated fatty acids. Selenium is also a part of the enzymes that deiodinate thyroid\nhormones. Generally, selenium acts as an antioxidant that works with vitamin E. Some epidemiologic\nstudies associate low selenium levels with cancer. In children with Down syndrome, selenium\nsupplements may help prevent bacterial infections. Plasma levels vary from 8 to 25 \n\u03bc\ng/dL, depending on\nselenium intake. Diagnosis is usually clinical; sometimes blood glutathione peroxidase is measured.\nDeficiency:\n Deficiency is rare, even in New Zealand and Finland, where selenium intake \nis 30 to 50\n\u03bc\ng/day, compared with 100 to 250 \n\u03bc\ng/day in the US and Canada. In certain areas of China, where intake\naverages 10 to 15 \n\u03bc\ng/day, selenium deficiency predisposes patients to Keshan disease, an endemic viral\ncardiomyopathy affecting primarily children and young women. This cardiomyopathy can be prevented\nbut not cured by sodium selenite supplements of 50 \n\u03bc\ng/day po. Patients receiving long-term TPN have\ndeveloped selenium deficiency with muscle pain and tenderness that responded to a selenomethionine\nsupplement. In Siberian Russia and China, growing children with selenium deficiency may develop\nchronic osteoarthropathy (Kashin-Beck disease). Selenium deficiency may contribute synergistically with\niodine deficiency to the development of goiter and hypothyroidism.\nDiagnosis is made clinically or sometimes by measuring glutathione peroxidase activity or plasma\nselenium, but neither of these tests is readily available. Treatment consists of sodium selenite 100 \n\u03bc\ng/day\npo.\nToxicity:\n At high doses (> 900 \n\u03bc\ng/day), selenium causes toxicity. Manifestations include hair loss,\nabnormal nails, dermatitis, peripheral neuropathy, nausea, diarrhea, fatigue, irritability, and a garlic odor of\nthe breath. Toxic levels of plasma selenium are not well defined.\nZinc\nZinc (Zn) is contained mainly in bones, teeth, hair, skin, liver, muscle, leukocytes, and testes. Zinc is a\ncomponent of several hundred enzymes, including many nicotinamide adenine dinucleotide (NADH)\ndehydrogenases, RNA and DNA polymerases, and DNA transcription factors as well as alkaline\nphosphatase, superoxide dismutase, and carbonic anhydrase. A diet high in fiber and phytate (eg, in\nwhole-grain bread) reduces zinc absorption.\nDeficiency:\n Dietary deficiency is unlikely in healthy people. Secondary zinc deficiency can develop in the\nfollowing:\n\u2022 Some patients with hepatic insufficiency (because the ability to retain zinc is lost)\n\u2022 Patients taking diuretics\n\u2022 Patients with diabetes mellitus, sickle cell disease, chronic renal failure, or malabsorption\n\u2022 Patients with stressful conditions (eg, sepsis, burns, head injury)\n\u2022 Elderly institutionalized and homebound patients (common)\nMaternal zinc deficiency may cause fetal malformations and low birth weight.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5. Mineral Deficiency & Toxicity\n106"}


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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 54, "chroma:document": "Zinc deficiency in children causes impaired growth and impaired taste (hypogeusia). Other symptoms and\nsigns in children include delayed sexual maturation and hypogonadism. In children or adults, symptoms\ninclude hypogonadism, alopecia, impaired immunity, anorexia, dermatitis, night blindness, anemia,\nlethargy, and impaired wound healing.\nZinc deficiency should be suspected in undernourished patients with typical symptoms or signs. However,\nbecause many of the symptoms and signs are nonspecific, clinical diagnosis of mild zinc deficiency is\ndifficult. Laboratory diagnosis is also difficult. Low albumin levels, common in zinc deficiency, make serum\nzinc levels difficult to interpret; diagnosis usually requires the combination of low levels of zinc in serum\nand increased urinary zinc excretion. If available, isotope studies can measure zinc status more\naccurately.\nTreatment consists of elemental zinc 15 to 120 mg/day po until symptoms and signs resolve.\nAcrodermatitis enteropathica\n (a rare, once fatal autosomal recessive disorder) causes malabsorption\nof zinc. Psoriasiform dermatitis develops around the eyes, nose, and mouth; on the buttocks; and in an\nacral distribution. The disorder also causes hair loss, paronychia, impaired immunity, recurrent infection,\nimpaired growth, and diarrhea. Symptoms and signs usually develop after infants are weaned from breast\nmilk. In such cases, doctors suspect the diagnosis. If deficiency is diagnosed, zinc sulfate 30 to 150\nmg/day po usually results in complete remission.\nToxicity:\n The recommended upper limit for zinc intake is 40 mg/day. Toxicity is rare. Ingesting doses of\nelemental zinc ranging from 100 to 150 mg/day for prolonged periods interferes with copper metabolism\nand causes low blood copper levels, RBC microcytosis, neutropenia, and impaired immunity; higher\ndoses should be given only for short periods of time and the patient should be followed closely. Ingesting\nlarger amounts (200 to 800 mg/day), usually by consuming acidic food or drink from a galvanized (zinc-\ncoated) container, can cause anorexia, vomiting, and diarrhea. Metal fume fever, also called brass-\nfounders' ague or zinc shakes, is caused by inhaling industrial zinc oxide fumes; it results in neurologic\ndamage. Symptoms usually resolve after 12 to 24 h in a zinc-free environment.\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 5. Mineral Deficiency & Toxicity\n107"}


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topic: persistent://default/default/7627526d-b178-41ff-8809-6c76a194a102
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{"source": "Nutritional Medical Reference/Nutritional Disorders.pdf", "page": 55, "chroma:document": "Chapter 6. Obesity and the Metabolic Syndrome\nObesity\nObesity is excess body fat; consequences depend not only on the absolute amount but also on\nthe distribution of the fat. Complications include cardiovascular disorders, diabetes mellitus,\nmany cancers, cholelithiasis, fatty liver and cirrhosis, osteoarthritis, reproductive disorders in\nmen and women, psychologic disorders, and premature death. Diagnosis is based on body\nmass index (BMI\u2014calculated from height and weight) and waist circumference. BP, fasting\nplasma glucose, and lipid levels should be measured. Treatment includes physical activity,\ndietary and behavioral modification, and sometimes drugs or surgery.\nPrevalence of obesity in the US is high and is increasing, particularly among children and adolescents\n(see\nTable 6-1\n).\nPrevalence is more than twice as high at age 55 as at age 20. Obesity is twice as common among women\nin a lower socioeconomic group as among those in a higher group. Prevalence among black and white\nmen does not differ significantly, but it is higher among black women than white women. More than 50%\nof black women \u2265 40 yr are obese; > 80% are overweight.\nIn the US, obesity and its complications cause as many as 300,000 premature deaths each year, making\nit second only to cigarette smoking as a preventable cause of death.\n[\nTable 6-1.\n Changes in Prevalence of Obesity According to Nhanes]\nEtiology\nAlmost all cases of obesity result from a combination of genetic predisposition and a chronic imbalance\nbetween energy intake, energy utilization for basic metabolic processes, and energy expenditure from\nphysical activity.\nGenetic factors:\n Heritability of BMI is about 66%. Genetic factors may affect the many signaling\nmolecules and receptors used by parts of the hypothalamus and GI tract to regulate food intake (see\nSidebar 6-1\n). Rarely, obesity results from abnormal levels of peptides that regulate food intake (eg, leptin)\nor abnormalities in their receptors (eg, melanocortin-4 receptor).\nGenetic factors also regulate energy expenditure, including BMR, diet-induced thermogenesis, and\nnonvoluntary activity-associated thermogenesis. Genetic factors may have a greater effect on the\ndistribution of body fat, particularly abdominal fat (see \nMetabolic Syndrome\n on p. \n64\n), than on the amount\nof body fat.\nEnvironmental factors:\n Weight is gained when caloric intake exceeds energy needs. Important\ndeterminants of energy intake include portion sizes and the energy density of the food. High-fat foods,\nprocessed foods, and diets high in refined carbohydrates, soft drinks, fruit juices, and alcohol promote\nweight gain. Diets high in fresh fruit and vegetables, fiber, and complex carbohydrates, with water as the\nmain fluid consumed, minimize weight gain. A sedentary lifestyle promotes weight gain.\nRegulatory factors:\n Prenatal maternal obesity, prenatal maternal smoking, intrauterine growth\nrestriction, and insufficient sleep can disturb weight regulation. About 15% of women permanently gain \u2265\n20 lb with each pregnancy. Obesity that persists beyond early childhood makes weight loss in later life\nmore difficult.\nDrugs, including corticosteroids, lithium, traditional antidepressants (tricyclics, tetracyclics, and\nmonoamine oxidase inhibitors [MAOIs]), benzodiazepines, and antipsychotic drugs, often cause weight\ngain.\nUncommonly, weight gain is caused by one of the following disorders:\nThe Merck Manual of Diagnosis & Therapy, 19th Edition Chapter 6. Obesity & the Metabolic Syndrome\n108"}


created_at: 2025-06-20 09:01:24
topic: persistent://default/default/1f920443-a7fb-48ff-bd9f-00de86a1df63
id: f7351f79-d87e-4bf2-8181-30b98948daa7
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{"original_content": "[['Inadequate absorption', ''], ['Common Causes', 'Decreased acid secretion in the elderly'], ['Other Causes', 'Blind loop syndrome, fish tapeworm infestation'], ['Less Common Causes', 'Chronic pancreatitis, gastric surgery, malabsorption syndromes, AIDS, use of certain drugs (eg, antacids, metformin), repeated exposure to nitrous oxide, Imerslund-Graesbeck syndrome']]", "source": "Nutritional Disorders.pdf", "page": 35, "type": "table", "chroma:document": "1. What are the common causes of inadequate absorption in the elderly?  \n2. What are some less common causes of inadequate absorption related to medical conditions or drug use?  \n3. How can blind loop syndrome or fish tapeworm infestation contribute to inadequate absorption?  "}


