nutri Flashcards
Triglyceride (TG) present in adipose tissue is the body’s major fuel reserve and is critical for survival during periods of starvation
The high energy density and hydrophobic nature of
TGs make them a five-fold better fuel per unit mass than glycogen.
TGs liberate 9.3 kcal/g when oxidized and are stored compactly as oil inside the fat cell
comparison, glycogen produces only 4.1 kcal/g on oxidation and is stored intracellularly as a gel
During endurance exercise, glycogen and TGs in muscle tissue provide an important source of fuel for working muscles
Daily total energy expenditure (TEE) has three components:
resting energy expenditure (REE) (≈70% of TEE);
the energy expenditure of physical activity (≈20% of TEE)
the thermic effect of feeding (≈10% of TEE), which is thetemporary increase in energy expenditure that accompanies enteral ingestion or parenteral administration of nutrients
REE represents energy expenditure while a person lies quietly awake in an interprandial state; under these conditions, about 1 kcal/kg body weight is consumed per hour in healthy adults.
The liver, intestine, brain, kidneys, and heart constitute roughly 10% of total body weight but account for about 75% of REE.
In contrast, skeletal muscle at rest consumes some 20% of REE, but represents approximately 40% of body weight
Adipose tissue consumes less than 5% of REE but usually accounts for greater than 20% of body weight.
accurate assessment of REE is best obtained by indirect calorimetry, in which in vivo energy expenditure is estimated by measuring carbon dioxide production and oxygen consumption
while the subject is at rest.
Although indirect calorimetry is considered a gold standard for determining REE, obtaining such a measurement is not always practical
Harris-Benedict and Mifflin equations are designed for use in adults, whereas the WHO formulas includes equations for both children and adults.
Protein energy malnutrition (PEM) and hypocaloric feeding without superimposed illness each decrease REE to values 10% to 15% below those expected for actual body size, whereas acute illness or trauma predictably increases energy expenditure
Highly trained athletes can increase their TEE 10- to 20-fold during athletic events
The energy expended during a particular physical activity is equal to (REE per hour) × (activity factor) × (duration of activity in hours).
TEE represents the summation of energy expended during all daily activities, including rest periods
Eating or infusing nutrients increases metabolic rate.
Dietary protein causes the greatest stimulation of metabolic rate, followed by carbohydrate
and then fat.
A meal containing all these nutrients usually increases metabolic rate by 5% to 10% of ingested or infused calories
In arriving at a nutritional plan for hospitalized patients, it is usually not necessary to obtain actual measurements of energy expenditure with a bedside indirect calorimeter
The increase in energy expenditure is roughly proportional to the magnitude of the stress
Thus, the total daily energy requirement of an acutely ill patient can be estimated by multiplying the predicted REE (as determined by the Harris-Benedict or WHO equations) by a stress factor:
In acutely ill hospitalized patients, it is not usually necessary to include an activity factor
An alternative and simple formula for adult inpatients,
although accompanied by some further loss in accuracy, is
20 to 25 kcal/kg of actual body weight (ABW)/day for unstressed or mildly stressed patients
25 to 30 kcal/ABW/day for moderately stressed patients
30 to 35 kcal/ABW/day for severely stressed patients
In using this formula, adjustments are necessary when the ABW is a misleading reflection of lean body mass.
An adjusted ideal body weight (IBW) should be substituted for ABW in obese individuals who are more than 30% heavier than their IBW (desirable body weights
Using an adjusted IBW helps prevent an overestimation of energy requirements and is calculated as:
Adjusted IBW = IBW + 0.5 (ABW − IBW)
Relative Thermic Effect of Various Levels of Physical Activity
Resting 1.0
Very light Standing, driving, typing 1.1-2.0
Light Walking 2-3 miles/hr, shopping, light housekeeping 2.1-4.0
Moderate Walking 3-4 miles/hr, biking, gardening, scrubbing floors
4.1-6.0
Heavy Running, swimming, climbing, basketball
6.1-10.0
In patients with large artifactual increases in weight due to extracellular fluid retention (e.g., ascites), the IBW should be used to estimate energy requirements rather than the ABW
The most accurate and extensively validated equation for predicting daily energy expenditure in ill patients is one that does not incorporate a stress factor; it does, however, require knowledge of the minute ventilation, so its use is restricted to patients on mechanical ventilation.
This formula (often referred to as the “Penn State Equation”)
Injury or Illness Relative Stress Factor*
Second- or third-degree burns, >40% BSA
1.6-2.0
Multiple trauma 1.5-1.7
Second- or third-degree burns, 20%-40% BSA
1.4-1.5
Severe infections 1.3-1.4
Acute pancreatitis 1.1-1.2
Second- or third-degree burns, 10%-20% BSA
1.2-1.4
Long bone fracture 1.2
Peritonitis 1.2
Uncomplicated postoperative state 1.1
*A stress factor of 1.0 is assumed for healthy controls.
significantly reduced in those randomized to intensive insulin therapy who maintained serum glucose levels below 111 mg/dL, compared with those whose glucose values were maintained below 215 mg/dL.
popular nutritional approach to such patients is
so-called hypocaloric feeding, in which only 60% to 70% of the estimated energy requirement (or 11 to 14 kcal/kg of ABW) is delivered in conjunction with 2 to 2.5 grams of protein/kg of IBW per day,
the latter minimizing the risk of producing net protein catabolism and loss of lean body mass purported advantages of hypocaloric feeding include improved glycemic control and prevention of metabolic complications like hypercapnia and hypertriglyceridemia.
Estimated Energy Requirements for Hospitalized Patients Based on Body Mass Index
Energy Requirements (kcal/kg/ day)*
<15 =35-40
15-19 =30-35
20-29 =20-25
≥30 =15-20
These values are recommended for critically ill patients and all obese patients; add 20% of the total calories when estimating energy requirements in non–critically ill patients.
Twenty different amino acids (AAs) are commonly found in human proteins.
Some AAs (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, and possibly arginine) are considered essential because their carbon skeletons cannot be synthesized by the body
The body of an average 75-kg man contains about 12 kg of protein. In contrast to fat and carbohydrate, there is no storage depot for protein, so excess intake is catabolized and the nitrogen component is excreted
The U.S. Recommended Daily Allowance (RDA) of protein has been established at 0.8 g/kg/day, which reflects a mean calculated requirement of 0.6 g/kg/day plus an added factor to take into account the biological
variance in requirement observed in a healthy population
Clinical Condition Daily Protein Requirement (g/kg IBW)
Normal 0.80
Metabolic stress 1.0-1.6
Hemodialysis 1.2-1.4
Peritoneal dialysis 1.3-1.5
As metabolic stress (and with it, metabolic rate) increases, nitrogen excretion increases proportionately; quantitatively, the relationship is approximately 2 mg nitrogen (N)/kcal of REE.
in metabolic stress, a larger proportion of the total substrate oxidized for energy is from protein.
The first is that illness, by increasing catabolism and metabolic rate, increases the absolute requirement
for protein and does so in a manner that is
roughly proportional to the degree of stress.
Second, because a greater proportion of energy substrate in acute illness comes from protein, nitrogen balance is more readily achieved if a larger proportion
of the total calories are from protein
Most patients with hepatic encephalopathy respond
to simple pharmacologic measures and, therefore, do not require protein restriction; those who do not respond may benefit from a modest protein restriction (≈0.6 g/kg/day)
Nitrogen (N) balance is commonly used as a proxy measure of protein balance
Every 6.25 g of administered protein (or AAs) contains approximately 1 g of N.
The additional 4 g of N loss incorporated into
the equation is intended to account for the insensible losses from the other sources listed and because urinary urea N only accounts for approximately 80% of total urinary nitrogen.
N balance is a suitable surrogate for protein balance, because roughly 98% of total body N is in protein, regardless of one’s health.
A positive N balance (i.e., intake > loss) represents anabolism and a net increase in total body protein, whereas a negative N balance represents net protein catabolism.
For example, a negative N balance of 1 g/day represents a 6.25 g/day loss of body protein, which is equivalent to a 30 g/day loss of hydrated lean tissue
Complete digestion of the principal dietary digestible carbohydrates— starch, sucrose, and lactose—generate monosaccharides (glucose, fructose, and galactose).
In addition, 5 to 20 g of indigestible carbohydrates (soluble and insoluble fibers) are typically
consumed daily.
glucose is the required or preferred fuel for red and white blood cells, the renal medulla, eye tissues, peripheral nerves, and the brain.
However, once glucose requirements for these tissues are met (≈150 g/day), the protein-sparing effects of carbohydrate and fat are similar
Dietary lipids are composed mainly of TGs,
which contain saturated and unsaturated long-chain fatty acids (FAs) of 16 to 18 carbons.
Use of fat as a fuel requires hydrolysis
of endogenous or exogenous TGs and cellular uptake of released FAs (see Chapter 102).
Long-chain FAs are delivered across the outer and inner mitochondrial membranes by a carnitine- dependent transport system.
Humans lack the desaturase enzyme needed to produce the n-3 (double bond between carbons 3 and 4) and n-6 (double bond between carbons 6 and 7) FA series.
Linoleic acid (C18:2, n-6) and linolenic acid (C18:3, n-3) are essential FAs and, therefore, should constitute at least 2% and 0.5%,
Adults who have moderate-to-severe fat malabsorption
(fractional fat excretion >20%) from other causes and
who are not TPN-dependent also frequently display a biochemical profile of EFAD
The biochemical diagnosis of EFAD is defined as an absolute and relative deficiency in the 2 EFAs in the plasma FA profile.
The full clinical EFAD syndrome includes alopecia, scaly dermatitis, capillary fragility, poor wound healing, increased susceptibility to infection, fatty liver, and growth retardation in infants and children
Major minerals are inorganic nutrients that are required in large (>100 mg/day) quantities and are important for ionic equilibrium, water balance, and normal cell function
Micronutrients (vitamins and trace minerals) are a diverse array of dietary components that are necessary to sustain health
none of the fat-soluble vitamins appear to serve as coenzymes, whereas almost all of the watersoluble
vitamins appear to function in that role
Calcium 1000-1200 mg
5-15
Metabolic bone disease, tetany, arrhythmias
24-hr urinary calcium = Reflects recent intake
Dual energy radiation absorptiometry= Reflects bone calcium content
Magnesium 300-400 mg
5-15
Weakness, twitching, tetany,
arrhythmias, hypocalcemia
Serum magnesium = May not reflect body stores
Urinary magnesium= May not reflect body stores
Phosphorus 800-1200 mg
20-60
Weakness, fatigue, leukocyte and platelet dysfunction, hemolytic anemia, cardiac failure, decreased oxygenation
Plasma phosphorus = May not reflect body stores
Potassium 2-5 g
60-100
Weakness, paresthesias, arrhythmias
Serum potassium =May not reflect body stores
Sodium 0.5-5 g
60-150
Hypovolemia, weakness
Urinary sodium May not reflect body stores
clinical evaluation is best
Vit A
Follicular hyperkeratosis and night blindness are early indicators.
Conjunctival xerosis, degeneration of the cornea (keratomalacia), and dedifferentiation of rapidly proliferating epithelia are later indications of deficiency.
Bitot spots (focal areas of the conjunctiva or cornea with foamy appearance) are an indication of xerosis.
Blindness caused by corneal destruction and retinal dysfunction may ensue.
Increased susceptibility to infection is also a consequence (1 μg of retinol is equivalent to 3.33 IU of
vitamin A; F, 700 μg; M, 900 μg)
Vit A
In adults, >150,000 μg may cause acute toxicity: fatal intracranial hypertension, skin exfoliation, and
hepatocellular injury. Chronic toxicity may occur with habitual daily intake of >10,000 μg: alopecia, ataxia, bone
and muscle pain, dermatitis, cheilitis, conjunctivitis, pseudotumor cerebri, hepatic fibrosis, hyperlipidemia, and hyperostosis are common. Single large doses of vitamin A (30,000 μg) or habitual intake of >4500 μg/ day during early pregnancy can be teratogenic. Excessive intake of carotenoids causes a benign
condition characterized by yellowish discoloration of the skin (3000 μg).
Retinol concentration in the plasma, as well as vitamin A concentrations in milk and tears, are reasonably accurate measures of status. Toxicity is best assessed by elevated levels of retinyl esters in plasma. A quantitative measure of dark adaptation for night vision and electroretinography are useful functional tests.
VitD D
Deficiency results in decreased mineralization of newly formed bone, a condition called rickets in childhood and osteomalacia in adults.
Deficiency also contributes to osteoporosis in later life and is common following gastric bypass procedures.
Expansion of epiphyseal growth plates and replacement of normal bone with unmineralized
bone matrix are the cardinal features of rickets;
the latter feature also characterizes osteomalacia.
Deformity of bone and pathologic fractures result.
Decreased serum concentrations of calcium and
phosphate may occur (1 μg is equivalent to 40 IU;
15 μg, ages 19-70; 20 μg, ages > 70).
Excess amounts result in abnormally high concentrations of calcium and phosphate in the serum; metastatic calcifications, renal damage, and altered mentation may occur (100 μg for ages >9).
Serum concentration of the major circulating metabolite, 25-hydroxyvitamin D, is an excellent indicator of systemic
status except in advanced kidney disease (stages 4-5), in which impairment of renal 1-hydroxylation results in dissociation of the mono- and dihydroxy vitamin concentrations; measuring the serum concentration of
1,25-dihydroxyvitamin D is then necessary.
Vitamin E
Deficiency caused by dietary inadequacy is rare in developed countries. Usually seen in premature
infants, individuals with fat malabsorption, and
individuals with abetalipoproteinemia.
RBC fragility occurs and can produce hemolytic
anemia. Neuronal degeneration produces
peripheral neuropathies, ophthalmoplegia, and
destruction of the posterior columns of the
spinal cord.
Neurologic disease is frequently
irreversible if deficiency is not corrected early
enough.
May contribute to hemolytic anemia and retrolental fibroplasia in premature infants. Has been reported to suppress cell-mediated immunity (15 mg).
Depressed levels of vitamin K-dependent procoagulants, potentiation of oral anticoagulants, and impaired leukocyte function have been reported. Doses of 800 mg/day have been reported to increase slightly the incidence of hemorrhagic stroke (1000 mg).
Plasma or serum concentration of alpha-tocopherol is used most commonly. Additional accuracy is obtained by expressing this value per mg of total plasma lipid. The RBC peroxide hemolysis test is not entirely specific but is a useful measure of the susceptibility of cell membranes to oxidation
Vit K
Deficiency syndrome is uncommon except in breast-fed newborns (in whom it may cause “hemorrhagic disease of the newborn”), adults who have fat malabsorption or are taking drugs that interfere with vitamin K metabolism (e.g., warfarin, phenytoin, broad-spectrum antibiotics), and individuals taking large doses of vitamin E and anticoagulant drugs. Excessive hemorrhage is the usual manifestation (F, 90 μg; M, 120 μg).
Rapid IV infusion of vitamin K1 has been associated with dyspnea, flushing, and cardiovascular
collapse; this is likely related to the dispersing agents in the dissolution solvent.
Supplementation may interfere with warfarin-based
anticoagulation.
Pregnant women taking large amounts of the
provitamin menadione may deliver infants with hemolytic anemia, hyperbilirubinemia, and kernicterus
(TUL not established).
Prothrombin time is typically used as a measure of functional vitamin K status; it is neither sensitive nor specific for vitamin K deficiency.
Determination of fasting plasma vitamin K is an accurate indicator.
Undercarboxylated plasma prothrombin is also an accurate metric, but only for detecting the deficient state, and is less widely available.
Thiamine (vitamin B1)
Classic deficiency syndrome (beriberi) remains
endemic in Asian populations consuming polished
rice diet.
Globally, alcoholism, chronic renal dialysis, and persistent nausea and vomiting after bariatric surgery are common precipitants.
High carbohydrate intake increases the need for B1. Mild deficiency commonly produces irritability, fatigue,
and headaches.
More pronounced deficiency can produce peripheral neuropathy, cardiovascular and cerebral dysfunction.
Cardiovascular involvement (wet beriberi) includes heart failure and low peripheral vascular resistance.
Cerebral disease includes nystagmus, ophthalmoplegia, and ataxia (Wernicke encephalopathy), as well as hallucinations, impaired short-term memory, and confabulation (Korsakoff psychosis).
Deficiency syndrome responds within 24 hr to parenteral thiamine but is partially or wholly irreversible after a certain stage (F, 1.1 mg; M, 1.2 mg).
Excess intake is largely excreted in the urine, although parenteral doses of >400 mg/day are reported to cause
lethargy, ataxia, and reduced tone of the GI tract (TUL not established).
The most effective measure of vitamin B1 status is the RBC transketolase activity coefficient, which measures enzyme activity before and after addition of exogenous
TPP;
RBCs from a deficient individual express a substantial
increase in enzyme activity with addition of TPP. Thiamine concentrations in the blood or urine are also measured
Riboflavin
(vitamin B2)
Deficiency is usually seen in conjunction with deficiencies of other B vitamins.
Isolated deficiency of riboflavin produces hyperemia
and edema of nasopharyngeal mucosa, cheilosis, angular stomatitis, glossitis, seborrheic
dermatitis, and normochromic, normocytic
anemia (F, 1.1 mg; M, 1.3 mg).
Toxicity has not been reported in humans (TUL not established).
Most common method of assessment is determining the activity coefficient of glutathione
reductase in RBCs (the test is invalid for individuals with glucose- 6-phosphate dehydrogenase
deficiency).
Measurements of blood and urine concentrations are less desirable methods.
Niacin (vitamin B3)
Pellagra is the classic deficiency syndrome and is
often seen in populations in which corn is the major
source of energy.
Still endemic in parts of China, Africa, and India. Diarrhea, dementia (or associated symptoms of anxiety or insomnia), and a pigmented dermatitis that develops in sun-exposed areas are typical features. Glossitis, stomatitis, vaginitis, vertigo, and burning dysesthesias are early signs.
Occasionally occurs in carcinoid syndrome, because tryptophan is diverted to other synthetic pathways (F, 14 mg; M, 16 mg).
Human toxicity is known largely through studies examining hypolipidemic effects; includes flushing,
hyperglycemia, hepatocellular injury, and hyperuricemia (35 mg).
Assessment of status is problematic; blood levels of the vitamin are not reliable.
Measurement of urinary excretion of the niacin
metabolites N-methylnicotinamide and 2-pyridone are thought to be the most effective means of assessment.
Pantothenic acid (vitamin B5)
Deficiency is rare; reported only as a result of
feeding semisynthetic diets or consumption
of an antagonist such as calcium homopantothenate, which has been used to treat Alzheimer disease.
Experimental isolated deficiency in humans produces fatigue, abdominal pain and vomiting, insomnia, and
paresthesias of the extremities (5 mg).
Diarrhea is reported to occur with doses exceeding 10 g/day (TUL not established).
Whole blood and urine concentrations of pantothenic
acid are indicators of status; serum levels are not thought to be accurate.
Pyridoxine
(vitamin B6)
Deficiency is usually seen in conjunction with other
water-soluble vitamin deficiencies. Stomatitis,
angular cheilosis, glossitis, irritability, depression,
and confusion occur in moderate to severe
depletion; normochromic, normocytic anemia
has been reported in severe deficiency.
Abnormal EEGs and, in infants, convulsions also have been reported.
Isoniazid, cycloserine, penicillamine, ethanol, and theophylline are drugs that can inhibit B6 metabolism (ages 19-50, 1.3 mg; >50 yr, 1.5 mg for women, 1.7 mg for men)
Chronic use with doses exceeding 200 mg/day (in adults) may cause peripheral neuropathies and photosensitivity (100 mg).
Many useful laboratory methods of assessment exist. Plasma or erythrocyte PLP levels are most common.
Urinary excretion of xanthurenic acid after an oral
tryptophan load or activity indices of RBC aminotransferases (ALT and AST) all are functional measures of B6-dependent enzyme activity
Biotin (vitamin B7)
Isolated deficiency is rare.
Deficiency in humans has been produced experimentally by dietary inadequacy, prolonged administration of TPN that lacks the vitamin, and ingestion of large quantities of raw egg white, which contains avidin, a protein that binds biotin with such high affinity that it renders it bio-unavailable.
Alterations in mental status, myalgias, hyperesthesias, and anorexia occur. Later, seborrheic dermatitis and alopecia develop. Biotin deficiency is usually accompanied by lactic acidosis and organic aciduria (30 μg).
Toxicity has not been reported in humans, with doses as high as 60 mg/day in children (TUL not established).
Plasma and urine concentrations of biotin are diminished in the deficient state. Elevated urine concentrations of methyl citrate, 3-methylcrotonylglycine, and 3-hydroxyisovalerate are also observed in deficiency
Folate (Vitamin B9)
Women of childbearing age are the most likely
to develop deficiency.
The classic deficiency syndrome is a megaloblastic anemia.
Hematopoietic cells in the bone marrow become
enlarged and have immature nuclei, reflecting
ineffective DNA synthesis.
The peripheral blood smear demonstrates macro-ovalocytes and polymorphonuclear leukocytes with an average of more than 3.5 nuclear lobes.
Megaloblastic changes in other rapidly proliferating epithelia (e.g., oral mucosa, GI tract) produce glossitis
and diarrhea, respectively.
Sulfasalazine and diphenytoin inhibit absorption, predisposing to deficiency.
Habitually low intake may increase the risk of colorectal cancer. (400 μg of dietary folate equivalent [DFE]; 1 μg folic acid = 1 μg DFE; 1 μg food folate = 0.6 μg DFE)
Daily dosage >1000 μg may partially correct the anemia of B12 deficiency and therefore mask
(and perhaps exacerbate) the
associated neuropathy.
Large doses are reported to lower seizure
threshold in individuals prone to
seizures.
Parenteral administration is rarely reported to cause allergic phenomena from dispersion agents
(1000 μg).
Serum folate levels reflect short-term folate balance, whereas RBC folate is a better reflection of tissue
status.
Serum homocysteine levels rise early in deficiency but
are nonspecific because B12 or B6 deficiency, renal insufficiency, and older age may also cause elevations.
Cobalamin (vitamin B12)
Dietary inadequacy is a rare cause of deficiency,
except in strict vegetarians.
The vast majority of cases of deficiency arise from loss of intestinal absorption—a result of pernicious anemia,
pancreatic insufficiency, atrophic gastritis, SIBO,
or ileal disease.
Megaloblastic anemia and megaloblastic changes in other epithelia (see “Folate”) are the result of sustained depletion.
Demyelination of peripheral nerves, the posterior
and lateral columns of the spinal cord, and
nerves within the brain may occur. Altered
mentation, depression, and psychoses occur.
Hematologic and neurologic complications may
occur independently.
Folate supplementation in doses exceeding 1000 μg/day may partly correct the anemia, thereby masking (or perhaps exacerbating) the neuropathic complications (2.4 μg
A few allergic reactions have been reported from crystalline B12 preparations and are probably due to impurities, not the vitamin (TUL not established).
Serum or plasma concentrations are generally accurate.
Subtle deficiency with neurologic complications is increasingly recognized among those ≥ 60 yr of
age, and can best be established by concurrently measuring the concentration of plasma B12 and (1) serum methylmalonic acid (MMA) or (2) holotranscobalamin II (holoTCII) because the latter are sensitive indicators of cellular deficiency.
A low-normal plasma B12 of 200-350 pg/mL (=148-258
pmol/L) with an elevated MMA or decreased holoTCII should be considered a state of deficiency
Ascorbic and dehydroascorbic acid (vitamin C)
Overt deficiency is uncommonly observed in
developed countries.
The classic deficiency syndrome is scurvy, characterized by fatigue, depression, and widespread abnormalities in connective tissues (e.g., inflamed gingivae, petechiae, perifollicular hemorrhages, impaired wound healing, coiled hairs, hyperkeratosis, and bleeding into body cavities).
In infants, defects in ossification and bone growth may occur. Tobacco smoking lowers plasma and leukocyte
vitamin C levels (F, 75 mg; M, 90 mg; the requirement for cigarette smokers is increased by 35 mg/day).
Quantities exceeding 500 mg/day (in
adults) sometimes cause nausea and
diarrhea.
Acidification of the urine with vitamin C supplementation, and the potential for enhanced
oxalate synthesis, have raised concerns regarding nephrolithiasis, but this has yet to be demonstrated.
Supplementation with vitamin C may interfere with laboratory tests based on redox potential (e.g., fecal occult blood testing, serum cholesterol,
serum glucose).
Withdrawal from chronic ingestion of high doses of vitamin C supplements should occur gradually over 1 month because accommodation does seem to occur, raising a concern for rebound scurvy (2000 mg).
Plasma ascorbic acid concentration reflects recent dietary intake, whereas leukocyte levels more
closely reflect tissue stores.
Plasma levels in women are ≈20% higher than in men for any given dietary intake.
Chromium Deficiency in humans is only described for patients on long-term TPN containing inadequate
chromium
Hyperglycemia or impaired glucose tolerance is uniformly observed
Copper Dietary deficiency is rare
it has been observed in premature and low-birth-weight infants exclusively fed a cow’s milk diet and in
individuals on long-term TPN without copper.
Clinical manifestations include depigmentation
of skin and hair, neurologic disturbances, leukopenia and hypochromic, microcytic anemia, skeletal abnormalities, and poor wound healing
The deficiency syndrome, except the anemia and leukopenia, is also observed in Menkes disease, a rare inherited condition associated with impaired copper uptake (900 μg).
Acute copper toxicity has been described after excessive oral intake and with absorption of copper salts applied to burned skin.
Toxicity may be seen with doses as low as 70 μg/kg/day.
Chronic toxicity is also described.
Wilson disease is a rare inherited disease associated with abnormally low ceruloplasmin levels and accumulation of copper particularly in the liver and brain,
Fluoride
Intake of <0.1 mg/day in infants and 0.5 mg/ day in children is associated with an increased incidence of dental caries.
Optimal intake in adults is between 1.5 and 4.0 mg/day (F, 3 mg; M, 4.0 mg).
Acute ingestion of >30 mg/kg body weight of fluoride is likely to cause death.
Excessive chronic intake (0.1 mg/kg/ day) leads to mottling of the teeth (dental fluorosis), calcification of tendons and ligaments, and exostoses, and may
increase brittleness of bones (10 mg).
Maternal iodine deficiency leads to fetal deficiency, which produces spontaneous abortions, stillbirths, hypothyroidism, cretinism, and dwarfism.
Rapid brain development continues through the second year, and permanent cognitive deficits may be induced by iodine deficiency during that period. In adults, compensatory hypertrophy of the thyroid
(goiter) occurs, along with varying degrees of
hypothyroidism (150 μg).
Large doses (>2 mg/day in adults) may induce hypothyroidism by blocking thyroid hormone synthesis.
Supplementation with >100 μg/day to an individual who was formerly deficient occasionally induces hyperthyroidism (1.1 mg).
Iron
Most common micronutrient deficiency in the
world.
Women of childbearing age constitute
the highest risk group because of menstrual
blood losses, pregnancy, and lactation.
Hookworm infection is the most common
cause worldwide.
The classic deficiency syndrome is hypochromic microcytic anemia.
Glossitis and koilonychia (spoon nails) are also
observed.
Easy fatigability often develops as an
early symptom before appearance of anemia.
In children, mild deficiency of insufficient severity to cause anemia is associated with behavioral disturbances and poor school performance (postmenopausal F, 8 mg; M, 8 mg; premenopausal F, 18 mg).
Iron overload typically occurs when habitual dietary intake is extremely high, intestinal absorption is excessive, repeated parenteral administration of iron occurs, or a combination of these factors exists.
Excessive iron stores usually accumulate in reticuloendothelial tissues and cause little damage (hemosiderosis).
If overload continues, iron will eventually begin to accumulate in tissues such as hepatic parenchyma, pancreas, heart, and synovium, damaging these
tissues (hemochromatosis).
Hereditary hemochromatosis arises as a result of homozygosity of a common recessive trait.
Excessive intestinal absorption of iron is observed in homozygotes (45 mg).
Negative iron balance initially leads to depletion of iron stores in the bone marrow; bone marrow biopsy and
the concentration of serum ferritin are accurate and early indicators of such depletion.
As deficiency becomes more severe, serum iron (SI) decreases and total iron binding capacity (TIBC) increases; an iron saturation (= SI/TIBC) of <16%
suggests iron deficiency.
Microcytosis, hypochromia, and anemia ensue in
latter stages of the deficient state.
Elevated levels of serum ferritin or an iron saturation >60% raises suspicion of iron overload, although systemic inflammation elevates serum ferritin level regardless of iron status.
Manganese
It is said to cause hypocholesterolemia, weight loss, hair and nail changes, dermatitis, and impaired synthesis of vitamin K–dependent proteins
Toxicity by oral ingestion is unknown in humans.
Toxic inhalation causes hallucinations, other alterations in mentation, and extrapyramidal movement disorders (11 mg).
Selenium
Such individuals have myalgias and/or cardiomyopathy.
Populations in some regions of the world, most notably some parts of China, have marginal intake of selenium.
It is in these regions of China that Keshan disease is endemic,
Toxicity is associated with nausea, diarrhea, alterations in mental status, peripheral neuropathy, and loss of hair and nails; such symptoms were observed in adults who inadvertently consumed between 27 and 2400 mg (400 μg
Zinc
Deficiency of zinc has its most profound effect
on rapidly proliferating tissues.
Mild deficiency causes growth retardation in children.
More severe deficiency is associated with growth
arrest, teratogenicity, hypogonadism and infertility,
dysgeusia, poor wound healing, diarrhea,
dermatitis on the extremities and around orifices,
glossitis, alopecia, corneal clouding, loss of dark
adaptation, and behavioral changes.
Impaired cellular immunity also is observed. Excessive loss of GI secretions (e.g., through chronic diarrhea or
fistulas) may precipitate deficiency.
Acrodermatitis
enteropathica is a rare recessively inherited
disease in which intestinal absorption of zinc is
impaired
Alkaline phosphatase is a zinc-dependent protein,
and therefore serum activity of the enzyme has sometimes been
proposed as a functional measure of zinc status.
Some reports have indicated that TPN solutions that deliver several-fold more manganese than what is recommended in
may lead to deposition of the mineral in the basal ganglia, with resulting extrapyramidal symptoms, seizures, or both.
The mean vitamin B12 status of most populations,
for example, declines significantly with older age, in large part because of the high prevalence of atrophic gastritis and its resultant impairment of protein-bound vitamin B12 absorption
Guidelines for Daily Administration of Parenteral
Micronutrients in Adults
A 1000 μg (= 3300 IU)
D 5 μg (= 200 IU)
E 10 mg (= 10 IU)
K 1 mg
Both fat- and water-soluble micronutrients are absorbed predominantly in the proximal small intestine, the only exception being vitamin B12, which is absorbed in the ileum.
The polyethylene glycol succinate form of vitamin E
(Nutr-E-Sol) is very effective in patients with severe fat malabsorption who cannot absorb conventional alpha-tocopherol
Maldigestion usually results from chronic pancreatic insufficiency, which, if untreated, frequently causes fat malabsorption and deficiencies of fat-soluble vitamins.
Vitamin B12 malabsorption also can be demonstrated in this setting, but clinical vitamin B12 deficiency is rare unless other conditions known to diminish its absorption are also present (e.g., atrophic gastritis or chronic administration of PPIs
Whether long-term administration of PPIs alone warrants occasional checks of vitamin B12 status is a matter of debate
Regardless, malabsorption of vitamin B12 from atrophic gastritis or with PPIs is confined to dietary sources of vitamin B12.
Monitoring of serum calcium levels is indicated in
the first few weeks of therapy with hydroxylated forms of vitamin D, because they are considerably more potent than vitamin D2 or D3, and risk of vitamin D toxicity exists
Regardless, malabsorption of vitamin B12 from atrophic gastritis or with PPIs is confined to dietary sources of vitamin B12.
Small supplemental doses of crystalline vitamin B12 are absorbed readily in both cases. Histamine-2 receptor antagonists also inhibit protein-bound vitamin B12 absorption, although the effect generally is believed to be less potent than with the PPIs.
Cholestyramine
Vitamin D, folate
Adsorbs nutrient, decreases absorption
Dextroamphetamine, fenfluramine, levodopa
Potentially all micronutrients
Induces anorexia
Isoniazid Pyridoxine Impairs uptake of vitamin B6
NSAIDs Iron GI blood loss
Penicillamine Zinc Increases renal excretion
PPIs Vitamin B12 Modest bacterial overgrowth, decreases gastric acid/ pepsin, impairs absorption
Sulfasalazine
Folate Impairs absorption and inhibits folate-dependent enzymes
During the first 24 hours of fasting, the most readily available energy substrates (i.e., circulating glucose, FAs and TGs, and liver and muscle glycogen) are used as fuel sources.
The sum of energy provided by these stores in a 70-kg man, however, is only about 5000 kJ (1200 kcal) and therefore is less than a full day’s requirements
Oxidation of FAs released from adipose tissue TGs accounts for about 65% of the energy consumed during the first 24 hours of fasting.
Approximately 15% of the REE is provided by oxidation
of protein
The relative contribution of gluconeogenesis to hepatic glucose production increases as the rate of hepatic glycogenolysis declines because the latter process becomes redundant; after 24 hours of fasting, only 15% of liver glycogen stores remain.
During short-term starvation (1 to 14 days), several adaptive responses appear that lessen the loss of lean mass.
A decline in levels of plasma insulin, an increase in plasma epinephrine levels, and an increase in lipolytic sensitivity to catecholamines stimulate adipose tissue lipolysis
A maximal rate of ketogenesis is reached by 3 days of starvation, and plasma ketone body concentration is increased 75-fold by 7 days
In contrast to FAs, ketone bodies can cross the blood-brain barrier and provide most of the brain’s energy needs by 7 days of starvation
Whole-body glucose production decreases by greater than 50% during the first few days of fasting because of a marked reduction in hepatic glucose output
During long-term starvation (14 to 60 days), maximal adaptation is reflected by a plateau in lipid, carbohydrate, and protein metabolism. The body relies almost entirely on adipose tissue for its fuel, providing greater than 90% of daily energy requirements
Muscle protein breakdown decreases to less
than 30 g/day, causing a marked decrease in urea nitrogen production and excretion.
The decrease in osmotic load diminishes urine volume to 200 mL/day, thereby reducing fluid requirements.
Total glucose production decreases to approximately 75 g/day, providing fuel for glycolytic tissues (40 g/day) and the brain (35 g/day) while maintaining a constant plasma glucose concentration.
Energy expenditure decreases by 20% to 25% at 30 days of fasting and remains relatively constant thereafter despite continued starvation
In humans, it has been proposed that there are certain
thresholds beyond which lethality is inevitable:
depletion of total body protein between 30% and 50% and of fat stores between 70% and 95%,
or reduction of BMI below 13 kg/m2 for men and 11 kg/m2 for women
Primary PEM is caused by inadequate intake of protein, calories, or both, or, less commonly, when the protein ingested is of such poor quality that one or more essential AAs becomes a limiting factor
in the maintenance of normal protein metabolism.
Secondary PEM is caused by illness or injury
Illness and injury also commonly induce anorexia (see later for mechanisms), so primary and secondary factors often act in concert to create PEM in the setting of illness.
Illness or injury may directly interfere with nutrient assimilation; for example, extensive ileal disease or resection may directly produce fat malabsorption and a caloric deficit.
The most common causes of secondary PEM, however, are the remarkable increases in protein catabolism and energy expenditure that occur as a result of a systemic inflammatory response
A healthy adult typically loses about 12 g N/day in urine, and excretion may increase to as much
as 30 g/day during critical illness.
Because 1 g of urinary N represents the catabolism of approximately 30 g of lean mass, it follows that severe illness may produce a daily loss of up to about 0.5 kg of lean mass as a result of excess protein catabolism
Most of this loss comes from skeletal muscle, where the efflux of AAs increases two- to six-fold in critically ill patients.
Over 95% of energy expenditure resides in the lean body mass, which, therefore, contains the bulk of metabolism that sustains homeostasis
kwashiorkor
“disease of the displaced child” because it was commonly seen after weaning
The presence of peripheral edema distinguishes
children with kwashiorkor from those with marasmus
and nutritional dwarfism. Children with kwashiorkor also have characteristic skin and hair changes
The abdomen is protuberant because of weakened abdominal muscles, intestinal distention, and hepatomegaly, but ascites is rare
Children with kwashiorkor are typically lethargic and apathetic, but become very irritable when held. Kwashiorkor most often occurs when a physiologic stress (e.g., infection) is superimposed on an already malnourished child.
Kwashiorkor is characterized by leaky cell membranes
that permit movement of potassium and other intracellular ions into the extracellular space, causing water movement and edema.
Kwashiorkor Appetite Poor Edema Present Mood Irritable when picked up, apathetic when alone Weight for age (% expected) 60-80 Weight for height Normal or decreased
Marasmus Appetite Good Edema Absent Alert Weight for age (% expected) <60 Weight for height Markedly decreased
Nutritional Dwarfism Appetite Good Edema Absent Alert Weight for age (% expected) <60 Weight for height Normal
Marasmus
Weight loss and marked depletion of subcutaneous fat and muscle mass are characteristic features of children with marasmus.
Ribs, joints, and facial bones are prominent, and the skin
is thin, loose, and lies in folds.
In contrast, the visceral protein compartment is relatively spared, a fact that often is reflected by a normal serum albumin level, which in turn sustains normal oncotic pressure in the vascular compartment, thus minimizing edema and helping to distinguish these children from those with kwashiorkor.
Nutritional Dwarfism
The child with failure to thrive may be of normal weight for height but have short stature and delayed sexual development.
Providing appropriate feeding can stimulate catch-up growth and sexual maturation.
The diagnosis of PEM is different in adults than in children, because adults do not grow in height. Therefore, undernutrition in adults causes wasting rather than stunting.
In addition, although pure forms of kwashiorkor and marasmus can occur in adults, contemporary studies of adult PEM in high-income societies typically focus on hospitalized patients with secondary PEM, coexisting illness or injury, and overlapping features of kwashiorkor and marasmus.
functional atrophy of the small intestinal mucosa, as evidenced by a loss of brush border enzymes and diminished integrity of the epithelial barrier.
Villus atrophy may also be observed with lack
of intestinal stimulation, but in the absence of PEM, the degree of structural atrophy is minor
