Nutrition and Metabolism Flashcards
TGs liberate ____ when oxidized and are stored compactly as oil inside the fat cell.
9.3 kcal/g
glycogen produces only ___ on oxidation and is stored intracellularly as a gel, containing approximately 2 g of water per gram of glycogen.
4.1 kcal/g
Daily total energy expenditure (TEE) has three components:
resting energy expenditure (REE) (≈70% of TEE); the energy expenditure of physical activity (≈20% of TEE);
and the thermic effect of feeding (≈10% of TEE), which is the temporary increase in energy expenditure that accompanies enteral ingestion or parenteral administration of nutrients.
Resting Energy Expenditure
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.
liver, intestine, brain, kidneys, and heart
constitute roughly 10% of total body weight but account for about 75% of REE.
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.
An accurate assessment of REE
best obtained by indirect calorimetry, in vivo energy expenditure is estimated by measuring carbon dioxide production and oxygen consumption while the subject is at rest.
The energy expended during a particular physical activity
is equal to (REE per hour) × (activity factor) × (duration of activity in hours)
Thermic Effect of Feeding
A meal containing all these nutrients usually increases metabolic rate by 5% to 10% of ingested or infused calories.
stress factor
TEE = REE × Stress 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 un- stressed or mildly stressed patients
25 to 30 kcal/ABW/day for moderately stressed patients
30 to 35 kcal/ABW/day for severely stressed patients
Adjusted IBW
Adjusted IBW = IBW + 0.5 (ABW−IBW)
Relative
Thermic Effect of Various Levels 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: basketball
6.1-10.0
In patients with large artifactual increases in weight due to extracellular fluid retention (e.g., ascites)
IBW should be used to estimate energy requirements
“Penn State Equation”) is:
TEE = (REE calculated by Mifflin equation × 0.96) + (Tmax × 167) + (Ve × 31) − 6212
Metabolic Stress Factors for Estimating Total Energy Expenditure in Hospitalized Patients
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
One reason for this conservatism is that acute illness and its management often exacerbate preexisting diabetes or produce de novo glucose intolerance.
hyperglycemia is a frequent consequence of enteral, and especially parenteral, nutrition.
Extremely tight control, with target range
a target range of 81 to 108 mg/dL
A panel of experts recently recommended instituting protocols to keep blood sugar levels at 150 mg/dL or lower in ICU patients, preferably by use of a continuous infusion of insulin, with monitoring every 1 to 2 hours so that appropriate adjustments can be made and blood sugar values less than 70 mg/ dL are avoided
Estimated Energy Requirements for Hospitalized Patients Based on Body Mass Index
<15 kg/m2: 35-40 kcal/kg/day
15-19kg/m2: 30-35kcal/kg/day
20-29 kg/m2: 20-25 kcal/kg/day
≥30 kg/m2: 15-20 kcal/kg/day
hypocaloric feeding,
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.
considered essential because their carbon skeletons cannot be synthesized by the body.
histidine, isoleucine, leucine, lysine, methio- nine, phenylalanine, threonine, tryptophan, valine, and possibly arginine
nonessential in most circumstances because they can be made from endogenous precursors or essential AAs
glycine, alanine, serine, cysteine, tyrosine, glutamine, glutamic acid, asparagine, and aspartic acid
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 bio- logical variance in requirement observed in a healthy population.
recommended Daily Protein Intake
Normal: 0.80g/kg IBW
Metabolic stress: 1.0-1.6g/kg IBW
Hemodialysis: 1.2-1.4g/kg/IBW
Peritoneal dialysis: 1.3-1.5g/kg/IBW
In normal adults, approximately _____ of total protein requirements should be in the form of essential AAs.
15-20%
Once adequate dialysis is available, protein delivery should be increased to the actual projected need,
including additional protein to compensate for losses resulting from dialysis
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
proxy measure of protein balance (i.e., whether the quantity of protein [or AAs] taken in is sufficient to prevent any net loss of protein).
Nitrogen Balance
N balance = (Grams of N administered as nutrition) − (Urinary urea N [g] + 4)
N balance (i.e., intake > loss) represents anabolism and a net increase in total body protein
positive N balance
represents net protein catabolism
negative N balance
Carbohydrates
Complete digestion of the principal dietary digestible carbohy- drates—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.
once glucose requirements for these tissues are met (≈150 g/day), the protein-sparing effects of carbohydrate and fat are similar.
Lipids
consist of TGs, sterols, and phospholipids.
they are essential FAs and, therefore, should constitute at least 2% and 0.5%, respectively, of the daily caloric intake to prevent a deficiency state.
Linoleic acid (C18:2, n-6) and linolenic acid (C18:3, n-3)
inorganic nutrients that are required in large (>100 mg/day) quantities and are important for ionic equilibrium, water balance, and normal cell function.
Major Minerals
MICRONUTRIENTS
micronutrients are distinguished from macronutrients (carbohydrates, fats, and proteins) and macrominerals (calcium, magnesium, and phosphorus).
Compelling evidence exists for the essential nature of 10 trace elements in humans
ron, zinc, copper, chromium, selenium, iodine, fluorine, manganese, molybdenum, and cobalt
Deficiency:
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).
Vitamin A
Vitamin A Toxicity:
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.
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).
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).
Vitamin D
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 D toxicity
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).
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).
Vitamin E
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.
Vitamin E toxicity
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).
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).
Vitamin K
Vitamin K toxicity
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).
Vitamin K
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.
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).
Thiamine (vitamin B1)
Deficiency (RDA)*
Classic deficiency syndrome (beriberi) remains endemic in Asian populations consuming polished
Thiamine (vitamin B1) toxicity
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.
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).
Riboflavin (vitamin B2)
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.
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).
Niacin (vitamin B3)
Niacin (vitamin B3) toxicity
Human toxicity is known largely through studies examining hypolipidemic effects; includes flushing, hyperglycemia, hepatocellular injury, and hyperuricemia (35 mg).
Niacin (vitamin B3) assessment
Measurement of urinary excretion of the niacin metabolites N-methylnicotinamide and 2-pyridone are thought to
be the most effective means of assessment.
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).
Pantothenic acid (vitamin B5)
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.
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).
Pyridoxine (vitamin B6)
Chronic use with doses exceeding 200 mg/day (in adults) may cause peripheral neuropathies and photosensitivity (100 mg).
Pyridoxine (vitamin B6) assessment
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.
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).
Biotin (vitamin B7)
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.
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).
Folate (Vitamin B9)
Folate (Vitamin B9) toxicity
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).
Folate assessment
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.
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 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).
Cobalamin (vitamin B12)
A few allergic reactions have been reported from crystalline B12 preparations and are probably due to impurities, not the vitamin (TUL not established).
Cobalamin (vitamin B12) toxicity
Cobalamin (vitamin B12) assessment
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.
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).
Ascorbic and dehydroascorbic acid (vitamin C)
Ascorbic and dehydroascorbic acid (vitamin C) toxicity
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).
Ascorbic and dehydroascorbic acid (vitamin C) assessment
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.
Deficiency in humans is only described for patients on long-term TPN containing inadequate chromium. Hyperglycemia or impaired
glucose tolerance is uniformly observed. Elevated plasma free fatty acid concentrations, neuropathy, encephalopathy, and abnormalities in nitrogen metabolism are also reported. Whether supplemental chromium may improve glucose tolerance in mildly glucose intolerant but otherwise healthy individuals remains controversial (F, 25 μg; M, 35 μg).
Chromium
Toxicity after oral ingestion is uncommon and seems confined to gastric irritation. Airborne exposure may cause contact dermatitis, eczema, skin ulcers, and bronchogenic carcinoma (No TUL established).
Chromium assessment
Plasma or serum concentration of chromium is a crude indicator of chromium status; it appears to
be meaningful when the value is markedly above or below the normal range.
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 anemia arises from impaired uptake of iron and is, therefore, a secondary form of iron deficiency anemia. 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).
copper
Acute copper toxicity
Acute copper toxicity has been described after excessive oral intake and with absorption of copper salts applied to burned skin. Milder manifestations include nausea, vomiting, epigastric pain, and diarrhea; coma and hepatocellular injury may ensue in severe cases. 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, eventually leading to damage of these 2 organs (10 mg).
