Medical Nutrition

Biochemical Assessment of Nutrition Status – Immunocompetence and Hematological Assessment

August 3, 2016 Hematology, Immunology, Medical Nutrition No comments , , , , , , , , , , , ,

Immunocompetence Assessment

Historically, evaluation of immunocompetence has been included as a part of any discussion of protein and nutrition assessment. This is logical, since adequate and appropriate immune function is dependent in part on adequate protein status. Protein deficiency routinely results in increased risk of infection as well as altered immune and inflammatory responses. But in clinical practice, the use of this type of nutrition assessment is complicated by the presence of disease and infection, which of course also affect all components of the immune system.

Nutrition Care Indicator: Total Lymphocyte Count (TLC) When evaluating a complete blood count (CBC) and differential count, calculaltion for TLC can be completed as follows:

TLC = WBC X % lymphocytes / 100

Total lymphocyte count will be affected by presence of infection, trauma, stress, and diseaes such as cancer and HIV, as well as medications that influence the immune system (e.g., chemotherapy and corticosteroids).

Nutrition Care Indicators for Hematological Assessment

Evaluation of erythrocytes (red blod cells, or RBC) can be an important component of nutrition assessment and is key to diagnosis of all anemia types. A complete blood count includes measurement of the total number of blood cells in the volume of blood. Many types of anemias exist, including those caused by deficiencies of iron, folate, or vitamin B12 and those arising from chronic diseases such as renal failure and congestive heart failure. Anermias are diagnosed by evaluation of the complete blood count and by the microscopic evaluation of the size, shape, and color of erythrocytes.

Hemoglobin (Hgb) Hemoglobin is a protein found in erythrocytes that functions to deliver oxygen to cells and to pick up carbon dioxide for expiration by the lungs. Measurement of hemoglobin is common in diagnosis of anemias, particularly iron-deficiency anemia. Additionally, hemoglobin is decreased in some chronic diseases and protein-energy malnutrition. Even though it is commonly measured, it is not the most sensitive or the most specific of hematological assessments of nutritional status. For example, in iron deficiency, iron stores may be depleted before serum hemoglobin levels will be affected.

Hematocrit (Hct) Hematocrit is defined as the percentage of blood that is actually composed of red blood cells. Hematocrit, like hemoglobin, will be decreased only in the final stage of iron deficiency. Hematocrit is affected by other nutrient deficiencies as well as by hydration status.

Mean Corpuscular Volume (MCV) Mean corpuscular volume is a measure of the average size of an individual red blood cell. A variety of anemias are characterized by changes in RBC size; for example, MCV is reduced in iron an copper deficiencies and elevated in folic acid and vitamin B12 deficiencies.

Mean Corpuscular Hemoglobin (MCH) Mean corpuscular hemoglobin is an estimate of the amout of hemoglobin in each cell. Thi value can reflect total serum hemoglobin levels. In some situations, however, MCH remains normal while the number of red blood cells is low, resulting in low total Hgb. Abnormalities are generally specific to iron deficiency and other nutritional anemias.

Mean Corpuscular Hemoglobin Concentration (MCHC) Mean corpuscular hemoglobin concentration also estimates the amount of hemoglobin in each red blood cell, but it expresses the value as a percentage.

Ferritin Ferritin is a protein that serves as a storage form of iron; therefore, serum ferritin is an estimate of iron stores. Ferritin is a sensitive and specific measure of iron status and will be one of the first indices to change in iron deficiency.

Transferrin Saturation As discussed earlier under "Protein Assessment," transferrin is a serum protein responsible for transport of iron systemically. Each molecule of transferrin can carry two molecules of iron. Under normal conditions, approximately 30% of iron binding sites on the transferrin molecule are saturated (i.e., have iron attached). The body's requirement for iron and overall iron status will be reflected by changes in transferrin saturation. When iron status is low, transferrin is less saturated. Transferrin is calculated by using the ratio of serum levels to total iron biding capacity (TIBC). TIBC is the test used to measure the saturation ability for transferrin. TIBC is higher during iron deficiency and lower after repletion. There are numerous equations to calculate transferrin from TIBC, but, as mentioned earlier, transferrin is not the most reliable indicator of protein status due to the effect of iron status.

Protoporphyrin When there is inadeuate iron available for hemoglobin synthesis, zinc is substituted fro iron within hemoglobin. Consequently, zinc protoporphyrin (the protein transporter for zinc) levels rise during iron deficiency and are considered a sensitive measure of iron-deficiency anemia.

Serum Folate Coenzymes associated with folate are necessary for amino acid metabolism, including many one-carbon transfer reactions such as the conversion of histidine to glutamate. Folate coenzymes also play a cruical role in the synthesis of purine needed for DNA. Folate deficiency can be diagnosed when megaloblastic, macrocytic red blood cells are present and serum folate and red cell folate are decreased, while serum B12 remains within normal limits. If folate levels are inadequate for conversion of histidine to glutamate, an intermediate product, formiminoglutamate (FIGlu), is formed. Urinary levels of FIGlu are thus elevated in folate deficiency and serve as a diagnostic tool for the condition.

Serum B12 Anemia associated with B12 (cobalamin) deficiency can be diagnosed in several ways. Clinically, it will be similar to folate deficiency but can be distinguished by measuring serum B12 levels, including serum total cobalamin and serum holo-transcobalamin II (the transport protein for B12). Biomarkers of B12 include homocysteine and methylmalonic acid levels, which change early on in the development of B12 deficiency. Historically, the Schilling test allowed for determination of defective absorption (gastric vs. intestinal). In this test, B12 is given as an injection and the amount excreted in urine is measured. This allows problems with different steps of B12 absorption to be distinguished. The Schilling test is no longer used in clinical practice, though to date no other test has replaced it specific function.

Biochemical Assessment of Nutrition Status – Protein Assessment

August 2, 2016 Clinical Skills, Critical Care, Medical Nutrition No comments , , , , , , , , , , , , , , , , ,

Protein Assessment

Protein's unique function in supporting cellular growth and development elevates its significance in nutrition assessment. Even though a large amout of protein is stored in muscle and viscera, the body strives to protect it from being used as an energy source. Under healthy conditions or normal energy deficits, additional energy is drawn from fat and glycogen stores. But when the body is under metabolic stress, it draws protein from the muscles to meet its needs. No specific laboratory value can determine the precise protein status of an individual. Each test has its own limitations. Therefore, a comprehensive nutrition assessment must use a battery of tests in order to delineate the changes that mark the development of a nutrient deficiency.

Historically, protein assessment has focused on evaluation of two compartments: somatic and visceral. Somatic protein refers to skeletal muscle. Visceral protein refers to nonmuscular protein making up the organs, structrual components, erythrocytes, granulocytes, and lymphocytes, as well as other proteins found in the blood.

Somatic Protein Assessment

In addition to using anthropometric measures such as midarm muscle area, midarm circumference, and overall body weight and subjective global assessment, biochemical tests such as creatinine height index and nitrogen balance can be used to more specifically analyze somatic protein status.

Screen Shot 2016-08-01 at 2.59.17 PMNutrition Care Indicator: Creatinine Hight Index Creatinine is formed at a constant daily rate from muscle creatine phosphate. Creatine phosphate group, which is stored in muscle, provides the phosphate group needed to regenerate ATP during high-intensity exercise. Creatinine is not stored in muscle but is cleared and excreted by the kidney. Daily urine output of creatinine can be correlated with total muscle mass.

For Creatinine Height Index, a 24-hour urine collection is performed and the total amount of creatinine excreted in that 24-hour period is compared with either a standard based on height or (as a percentage) to a standard excretion for a particular reference individual of a specific height, gender, and age.

In Table 3.8, expected creatinine excretion is shown for various heights. Creatinine height index (CHI) is usually expressed as a percentage of a standard value and is calculated with the following equation:

CHI = 24-hour urine creatinine (mg) / expected 24-hour urine creatinine (mg) x 100

A value calculated to be 60%-80% of the standard suggests mild skeletal muscle depletion, 40%-59% suggests moderate skeletal muscle depletion, and <40% is considered to be a severe loss of skeletal muscle.

One limitation of this measurement is that its accuracy depends on a complete collection of urine for 24 hours, which is a common source of error and makes the test more difficult to conduct. Interpretation of this test must also take into accouont the fact that creatinine excretion can be either higher or lower than the standard depending on certain clinical conditions. Creatinine excretion is increased by meat consumption, sepsis, trauma, fever, and strenuous exercise, and during the second half of the menstrual cycle. Creatinine excretion is decreased with compromised renal function, low urine output, aging, and muscle atrophy unrelated to malnutrition. Furthermore, standards that are used do not account for creatinine excretion changes with age, disease, physical training, frame size, or weight status.

Nutrition Care Indicator: Nitrogen Balance In healthy individuals, nitrogen excretion should be equal to nitrogen intake – thus indicating a state of nitrogen balance. A negative nitrogen balance develops when nitrogen excretion is greater than nitrogen intake, indicating catabolism or inadequate nitrogen intake, whereas a positive nitrogen blance occurs when nitrogen intake is greater than excretion. Measuring nitrogen balance assesses overall protein status. Additionally, it can serve as a metod of assessing the effectiveness of a nutrition intervention. Nitrogen balance is not routinely used for all acute-care patients but is more common in critical care, with nutrition support, and in research settings.

In order to measure nitrogen balance, the dietary intake of protein for a 24-hour period is estiamted while a 24-hour urine collection is gathered to measure total excretion of nitrogen. Nitrogen loss through other routes such as fecal excretion, normal skin breakdown, wound drainage, and nonurea nitrogen is estimated using a constant value of either 3 or 4. The following equation is used for calculation (6.25 g protein = 1 g nitrogen):

N2 balance = dietary protein intake / 6.25 – urine urea nitrogen – 4

Limitations of measuring nitrogen balance include the inherent error of 24-hour urine collection, failure to account for renal impairment, and inability to measure nitrogen losses from some wounds, burns, diarrhea, and vomiting. Nitrogen intake may also pose difficulties. Oral protein intake may be difficult to measure consistently and accurately except when the pateint is exclusively on enteral or parenteral nutrition support.

Visceral Protein Assessment

As stated previously, visceral protein refers to nonskeletal protein making up the organs, structrual components, erythrocytes, granulocytes, and lymphocytes, as well as other proteins found in the blood. Thus, visceral protein assessment indirectly measures these protein stores by assessing proteins made by these organs (primarily the liver) and present in blood or lymph fluid. Theoretically, serum protein measurement is affected by a change in the amount of amino acids needed for protein synthesis by the liver. Thus, a change in serum protein levels would be consistent with changes in visceral protein status. However, the synthesis rate of these transport proteins can be affected by factors other than protein intake or protein requirements. In general, transport protein synthesis is inhibited when the acute-phase protein synthesis rate is increased in response to inflammation, stress, or trauma. In the acute care setting where most patients are affected by these conditions, using transport proteins to measure protein status becomes difficult. The sensitivity and specificity of these assessment measures are often determined by the "half-life" of the protein. Half-life, in this clinical situation, means the amount of time it takes for half of the protein to be either eliminated or broken down by the body. Therefore, actual changes in serum levels will be reflected mroe quickly in proteins with a shorter half-life than in those with a longer half-life.

Acute-phase proteins are defined as "those whose plasma concentration increases (positive acute-phase proteins) or decreases (negative acute-phase proteins) by at least 25%" during inflammation, illness, and/or metabolic stress. C-reactive protein (CRP) is a common indicator for inflammation that has also been correlated with visceral protein markers. Increasing levels of CRP, indicating acute inflammation, are consistent with lower visceral protein markers as well as poor outcomes for the individual.

Nutrition Care Indicator: Albumin Albumin is probably the most well-known measure of visceral protein status even though it is not the best. It is also the most abundant serum protein. Approximately 60% of the albumin in the body is found in extravascular spaces – in skin, muscle, and organs. The remaining albumin is found within the vascular space, which allows for its measurement. Normal serum levels of albumin are >=3.5 g/dL. Synthesized by the liver (120-170 mg/kg/day), albumin serves many significant functions within the body, most commonly as a transport protein and as a component of vascular fluid and electrolyte balance. Decreases in serum albumin occur due to a decreased synthesis rate, an increased degradation rate, or a change in fluid distribution (either total volume or between compartments). Using albumin as a nutritional assessment marker in acute care is complicated by the fact that most patients are experiencing at least one of these factors; thus, albumin changes often reflect illness and not necessarily nutritional status.

Albumin has been the subject of significant nutrition research and thus serves as a good prognostic screening tool, though it is not as reliable in the acute care setting as an overall indicator of protein and nutritional status due to the effects of disease, inflammation, hydration, and numerous other factors. Still, because it is easily measured and has an abundant body pool, albumin is readily available in the lab reports at the acute care setting. Decreased albumin levels have been correlated with increased morbidity, mortality, and length of hospital stay.

Some of the same factors contribute to its limitations as well. 1)Albumin has a long half-life (approximately 20 days), which decreases its sensitivity to short-term changes in protein status or to short-term interventions to improve protein status. 2)Albumin synthesis is also affected by acute stress and the inflammation response. 3)Albumin loss occurs with burn injuries, nephrotic syndrome, protein-losing enteropathy, and cirrhosis. 4)Other medical conditions that may result in hypoalbuminemia include infection, multiple myeloma, acute or chronic inflammation, and rheumatoid arthritis. 5)Levels also decrease with aging. On the other hand, 6)albumin levels will be higher with dehydration and when individuals are prescribed anabolic hormones and corticosteroids. Albumin levels must be interpreted carefully – the levels are a better indicator of stress and inflammation than of overall protein nutrition, even though they historically have been widely used for that purpose.

Nutrition Care Indicator: Transferrin Synthesized by the liver, transferrin serves as a transporter for iron throughout the body. It can also serve as an indicator of protein status because it has a shorter half-life (8-10 days) and thus is sensitive to acute changes in protein intake or requirments. Normal serum levels are 215-380 mg/dL. Transferrin can be measured directly or calculated from total iron binding capacity (TIBC) with the use of the following equation: Transferrin saturation (%) = (Serum iron level X 100%) / TIBC.

Transferrin's primary limitation is that its concentration is directly affected by iron status. When iron stores are decreased, transferrin levels will increase to accommodate the need for increased levels of transport. Other disease states such as hepatic and renal disease, inflammation, and congestive heart failure can also affect transferrin levels.

Nutrition Care Indicator: Prealbumin (Thyroxine-Binding Prealbumin or Transthyretin) Prealbumin is another example of an acute-phase transport protein synthesized by the liver. Prealbumin is responsible for transport of thyroxine and is associated with retinol-binding protein.

Research has shown that because of its very short half-life (2 days), prealbumin levels respond to short-term modifications in nutritional intake and interventions. Prealbumin is a more expensive test than albumin, but research has indicated that if it were used routinely during admission screening, approximately 44% more hospitalized patients would be identified as being at nutritional risk. The clinician evaluating prealbumin should recognize that levels are inceased with renal disease and Hodgkin's disease, and decreased with liver disorders such as hepatitis or cirrhosis, malabsorption, and hyperthyroidism. Furthermore, like albumin, prealbumin levels may decrease as a result of illness and inflammation and not necessarily malnutrition.

PS: 1/5-life of nutrition care indicators, albumin 193 hrs; transferrin 70 hrs; prealbumin 15 hrs; RBP 4 hrs.

Nutrition Care Indicator: Retinol-Binding Protein (RBP) Retinol-binding protein, synthesized by the liver, is an acute-phase respondent and serves as the transport molecule for vitamin A (retinol). RBP has the smallest body pool and shortest half-life (12 hours) of the serum proteins.

RBP is considered to be one of the more sensitive indicators of protein status in the non-critical ill. Theoretically, it should reflect short-term changes and responses to nutrition support interventions. Lee and Nieman note that it is most likely a better measure of recent dietary intake than an indicator of overall nutrition status. The literature does not support its use preferentially over other measures of serum proteins. Note that RBP levels are elevated with renal failure and decreased with hyperthyroidism, liver failure, vitamin A deficiency, zinc deficiency, and metabolic stress.

Nutrition Care Indicator: C-Reactive Protein (CRP) C-reactive protein is a positive acute-phase protein that is released during periods of inflammation and infection. As the levels of acute-phase protein increase, hepatic reprioritization decreases synthesis of other transport proteins, such as prealbumin or albumin. Increasingly, CRP is being used to investigate the contribution of inflammation to malnutrition syndromes. Since albumin and prealbumin levels may be reduced by the inflammatory process, they are not reliable prognostic indicators during periods of inflammation and infection; in these situations, the CRP level becomes a component of nutrition assessment. Higher CRP levels are assocaited with increased nutritional risk during stress, illness, and trauma.

Estimate the Energy Requirements

February 5, 2016 Medical Nutrition No comments , , , , , , ,

The total amount of energy required by an individual is the sum of three basic components: basal energy expenditure (BEE) or basal metabolic rate (BMR) + energy for physical activity or exercise (PA) + thermic effect of food (TEF) 5 total energy expenditure (TEE). Basal energy expenditure is de ned as energy used for physiological functions that maintain life, such as respiration and heartbeat, and accounts for approximately 60% of an individual’s energy requirement. When the term basal energy expenditure is used, it refers to a measurement of oxygen consumed by a patient who has gone without food for at least 12 hours and has been lying down with little movement in a constant-temperature environment overnight.68 Additionally, during the actual measurement, the patient should not be moving, talking, sleeping, or using muscles other than those for breathing (i.e., be completely still and relaxed). Due to these strict measurement requirements, actual basal expenditure is in a practical sense theoretical and thus di cult to measure.  erefore, in many discussions regarding energy requirements, the term REE (resting energy expenditure) or RMR (resting metabolic rate) is used. Resting refers to measurement condi- tions where the individual is resting in a comfortable position without any other restrictions. RMR is usually estimated to be approximately 10% higher than BMR/BEE.

Physical activity (PA) is the most variable portion of an individual’s energy needs and  uctuates depending on the type, duration, and intensity of physical activity. In most individuals, PA accounts for approximately 15%–20% of energy requirements. TEF is estimated to be approximately 10% of an individual’s caloric intake and represents the energy needed for absorption, transport, and metabolism of nutrients.

Measuring or Estimating the Resting Energy Expenditure

There are three different ways to calculate the resting energy requirements, including:

  • Indirect calorimetry measurement
  • Equations estimation
  • DRI based method

Energy requirements could be accurately measured or be approxmiately estimation. The most accurate method of measuring REE/RMR (resting energy expenditure/resting metabolic rate) in a clinical setting is to use indirect calorimetry. The rationale of measuring energy requirements lies the fact and principle that the amount of oxygen and carbon dioxide in both inspired and expired air (VO2 and VCO2 or respiratory quotient [RQ]) are measured, and the volume (V) of gas exchanged is equated to known energy constants (specific numbers of kcal per mL of oxygen consumed). These values are then converted to REE/RMR using computer software within the measuring equipment. Calculations are based on the Weir equation: REE (kcal/day) = 1.44 x (3.9 x VO2 + 1.1 x VCO2). The literature recommends that nutrition support be provided at 100% of the measured RMR with the following substrate recommendations: carbohydrate at 50%, lipid at 20%-30%, and protein at 15%-20% of total kcal.

Screen Shot 2016-02-04 at 2.44.46 PMBecause the measuring of energy requirements needs special equipment, its routine use is limited. It is more common in clinical situations to calculate an estimation of an individual's energy requirements and, therefore, clinicians must reply on prediction equations. The method of estimation will vary depending on whether the patient is an adult or child; in a steady healty state or acutely ill; and independently breathing or mechanically ventilated.

A review of the literature reveals significant discussion of and attempts to determine the most accurate equations for use in these populations. AND (Academuy of Nutrition and Dietetics), through its Evidence Analysis Library, recommends that the Mifflin-St. Jeor equation be used to predict resting metabolic rate in both healthy obese and healthy non-obese Americans. The AND Evidence Analysis work group could not support the use of the Harris-Benedict, Ireton-Jones, or Fick equations in hospitalized, critical ill populations.

The Dietary Reference Intakes for macronutrients are standards of  intake that are age and gender specific and are designed to meet the nutrient requirements of about 98% of the healthy population. The DRI also include Estimated Energy Requirements (EER) that provide guidelines to meet the energy needs of approximately 50% of the healthy population. Because energy requirements vary considerably from individual to individual, the EER values are not meant to be goals of nutrient intake for individuals and hence are not recommended for estimating patient's energy requirements in a clinical setting. The DRI based energy requirements calculator is available on USDA at Note that this online calculator includes the activity factor.

Activity and Metabolic Stress Factors

Activity Factor

After resting energy expenditure has been determined, energy used in activity also must be estimated in order t oestimate total energy requirements. Previously activity and stress factors have been used to account for the metabolic stress of certain disease states and injuries. These have not been validated and are not recommended for practice.

There are many methods used to estimate the amount of energy needed for physical activity, especially in the nonhospitalized population. One total energy requirement formula developed by the Food and Nutrition Board incorporates a physical activity coefficient. Both the CDC and the American College of Sports Medicine use the exercise metabolic rate, or MET, to estimate the amount of energy used in various physical activities. One MET is equivalent to energy expenditure while sitting quietly, which for the average adult approximates 3.5 mL of oxygen uptake per kilogram of body weight per minute (One MET is approximately equal to 3.5 mL of oxygen uptake/VO2 per kilogram per minute, and that is 1.2 kcal/min for a 70-kg individual).

PS: Metabolic Equivalents (METs)
The impact of various physical activities is often described and compared in terms of METs (i.e., multiples of an individual’s resting oxygen uptake), and one MET is defined as a rate of oxygen (O2) consumption of 3.5 ml/kg/min in adults. Taking the oxygen energy equivalent of 5 kcal/L consumed, this corresponds to 0.0175 kcal/minute/kg (3.5 mL/min/kg x 0.005 kcal/mL). A rate of energy expenditure of 1.0 MET thus corresponds to 1.2 kcal/min in a man weighing 70 kg (0.0175 kcal/kg/minute x 70 kg) and to 1.0 kcal/minute in a woman weighing 57 kg (0.0175 kcal/kg/min x 57 kg). (Source:

Stress Factors

Disease, infection, and trauma can affect an individual's energy requirements. Hospitalized patients can be hypermetabolic; estimation of their energy needs should take this fact into account. The common practice of using a stress factor to calculate energy needs has not been validated consistently, and thus estimations of energy requirements during stress have been modified considerably over the past decade as understanding of the stress response has deepened. Overfeeding may be much more detrimental than underestimation of energy needs.

Causes of Metabolic Stress

  • Trauma
  • Closed head injury
  • Burns
  • Severe inflammation
  • Cancer
  • Sepsis
  • Hypoxic injury
  • Major surgery

The degree of metabolic stress generally correlates with the seriousness of the injury (Glasgow Coma Scale and APACHE II score are commonly used to rank the severity of injury).

Estimate the Energy of Exercise via MET

Energy of 1 MET should be '1 x 0.0175 x body weight (kg) x exercise duration (min)'. So for a 70-kg person to swim for 1 hour the enerugy expenditure shall be 7.0 x 0.0175 x 70 x 60 = 514.5 kcal.

Note that capacity of oxygenation delivery decreases as age grows so you must make sure the activiy perscribed won't expense a oxygen higher than the maximum value.

Unfinished Contents

1.How to estimate the energy requirements in patients with clinical conditions that affect energy requirement?

2.How to estimate the energy requirements needed by common physical activities? (Transform MET values into calories)