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.
Nutrition 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.