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INTRODUCTION AND AIM OF WORK
REVIEW OF LITERATURE
- Malnutrition in COPD patients
- Adverse effects of malnutrition in COPD patients
- Nutritional assessment
- Tumour-necrosis factor-alpha (TNF-)
- Nutritional interventions in COPD patients
PATIENTS AND METHODS
SUMMARY AND CONCLUSION
All gratitude is to Allah almightly firstly and lastly. Many thanks for persons who were assigned to give me a precious hand so as to be able to fulfill this study.
I would like to express my profound gratitude and appreciation to Assitant Professor Olfat Moustafa El-Shinnawy, Assistant Professor of Chest diseases, Faculty of Medicine, Assiut University; for her supervision in this thesis, helping me in understanding many obscure points, continuous encouragement and support during conduction of this study.
I am deepty thankful to Assistant Professor Suzan Salama Sayed, Assistant Professor of Chest Diseases, Faculty of Medicine, Assiut University; for her sincere guidance, constructive criticism, meticulous help in every step in this work, great effort and indispensable support in revising this study.
I would like to express my profound gratitude to Assistant Professor Maha Atwa M. Ibraheem, Assistant Professor of Clinical Pathology, Faculty of Medicine, Assiut University; for her generous help in estimation of laboratory data for the studied groups; valuable advice and deep support during conduction of this thesis.
A wish to express my deep thanks to Professor Ahmed Hamed Osman, Professor and Head of Chest Department, Faculty of Medicine, Assiut University; for his kind support and continuous assistance all through this work.
Finally; I would like to express my great thanks to all patients included in this study; who taught me by their courage and suffering, to my parents and my wife who unselfishly endured my endeavours; all residents and nursing staff in the Chest Department, Laboratory technicians and every person supported and helped me in achieving this work.
Sherif Ahmed Abdel Wahab
Abbildung in dieser leseprobe nicht enthalten
Weight loss is a common feature in patients with chronic obstructive pulmonary disease (COPD) (Schols et al., 1993). The clinical importance of weight loss; particularely loss of fat-free mass (FFM) has been demonstrated in its adverse effects on physical performance and quality of life (Goris et al., 1997). Moreover; weight loss and a low body weight are unfavorable prognostic factors in survival, independent of lung function (Schols et al., 1998).
Mechanisms of malnutrition in those patients are not fully understood. Several factors have been implicated. Increased resting energy expenditure (REE) contributes the main hypothesis for weight loss in COPD patients. However, not all patients with COPD who lose weight are hypermetabolic (Congleton et al., 1993).
Recent data have shown that a systemic inflammatory response is present in patients with COPD (Schols, et al., 1996). A clear evidence for a relationship between weight loss and plasma tumour necrosis factor-alpha (TNF-) has been shown in COPD patients (Di Francia et al., 1994 and de Godoy et al., 1996).
TNF- produces a cachexia-like syndrome in animal models and has been implicated as a mediator of cachexia in several clinical conditions including cancer, chronic heart failure, cystic fibrosis and anorexia nervosa (Balkwill et al., 1987 and Norman et al., 1991).
Nutritional assessment for COPD patients is essential; to identify those individuals who will benifit from nutritional support therapies and to determine baseline values to measure the effectiveness of nutritional intervention (Veldee et al., 1994). It includes several methods, no simple recommendation can be given regarding the best method for nutritional assessment (Pingleton et al., 1998).
Because of the negative impact of malnutrition on the respiratory system in COPD patients, contributing to morbidity and mortality; it's valuable to include management strategies that increase energy balance in order to increase weight and fat-free mass in those malnourished COPD patients (Ferreira, et al., 2001).
The aim of this study is to determine the most valuable measurements to assess the nutritional status of COPD patients; as regards the anthropometric measurements, the somatic and visceral proteins and markers of inflammation; and to evaluate the correlation between serum TNF- levels and weight loss among those patients; as a trial to improve their clinical prognosis and quality of life.
The guidelines published by the American Thoracic Society (ATS) define COPD as "a disease state characterized by the presence of airflow obstruction due to chronic bronchitis or emphysema; the air flow obstruction is generally progressive, may be accompanied by airway reactivity, and may be partially reversible"(American Thoracic Society, 1995).
Patients are considered to be underweight if their body weight is 90% than their ideal body weight (IBW, 1983 Metropolitan Life Insurance Tables), or if their body mass index (BMI) weight/height squared is < 20 Kg/m2. (Metropolitan Life Insurance Company 1983 and World Health Organization, 1990).
In a study by deGodoy: et al., 1996; COPD patients were identified prospectively as "weight losers" if they reported > 5% weight loss during the preceding year or as " weight stable" if their body weight fluctuated 5%.
As many as 25 percent of outpatients with COPD may be malnourished, and almost 50 percent of patients with COPD who were admitted to the hospital have evidence of malnutrition. The incidence of malnatrition in critically ill patients with COPD and acute respiratory failure is 60 percent (Driver, et al., 1982). It was reported that; patients with COPD often lose weight and, depending on the population studied and the indicator used to determine the nutritional status, between 19 and 60% of patients are classified as malnourished (Laaban, et al., 1993). Malnutrition seems to affect emphysematous patients more than those with chronic bronchitis; Hughli; et al. (1991) reported that emphysematous patients are more frequently undernourished than those suffering form chronic bronchitis. Also, Schols, et al. (1999) reported that emphysematous patients were characterized by a lower body mass index due to a lower fat mass (FM) and by lower mean (detectable) leptin concentrations compared with bronchitic patients; and a significant partial correlation coefficient between leptin and serum tumour necrosis factor-alpha receptors 55 (STNF-R55) adjusted for FM and oral corticosteroid use was seen in emphysema but not in chronic bronchitis. (disease-subtype was defined by high-resolution computed tomography; HRCT).
Weight loss in COPD patients seems to involve both decrease in fat mass and fat free mass (FFM); Schols et al.; 1993 demonstrated that wight loss in COPD patients involves both decrease in fat mass and wasting of FFM. Also; Congleton, 1999 reported that both fat mass and fat-free mass become depleted, and that loss of FFM is the more important and appears to be due to a depression of protein synthesis.
Mechanisms of weight loss in COPD patients:
The various mechansims involved in COPD malnutrition are not fully understood (Laaban, et al., 1997 and Schols, et al., 2000).
Weight loss is generally considered as the result of an imbalance between energy intake and expenditure Malnutrition occurs when energy expenditure exceeds energy intake.
Increased resting energy expenditure (REE) contributes the main hypothesis for weight loss in COPD patients. However, not all patients with COPD who lose weight are hypermetabolic (Congleton, et al., 1993).
Possible mechanisms include:
(1) Decreased food intake: (Caloric intake)
A variety of reports have examined caloric intake in malnourished COPD patients; Hunter and Coworkers (1981) estimated that caloric intake in 18 underweight COPD patients was 44% greater than the recommended daily allowance, based on dietary recall data. In a study of 41 malnourished patients with emphysema, Otte and colleagues 1989, found a high habitual energy intake relative to calculated basal energy expenditure. Also estimates of mean daily caloric intake for patients with severe COPD and recent weight loss approximates 140% of the basal energy expenditure (BEE) as estimated from the Harris Benedict equation (Wilson, et al., 1986). On the other hand, Openbrier and associates 1983; reported no differences in daily caloric intake between adequately nourished and undernourished COPD patients. Also, in a study included 16 COPD patients who had >5% weight loss; Braun and Coworkers 1984 found an adequate caloric intake based on an estimated daily caloric requirments determined from calculated basal energy expenditure.
Difficulties can arise in determining the adequacy of caloric intake and in comparing results between studies because of inaccuracy of patient recall and dietary recording, and differences in the method of determing energy expenditure (Ryan et al., 1993).
Notably; Harris-Benedict formula used for calculation of basal metabolic rate (BMR) provides an under-estimated measure. BMR is more accurately assessed by indirect calorimetry (Lamisse, 2000).
Limtation of food intake in COPD patients may be due to: eating and swallowing which worsen dyspnea and arterial oxygen desaturation, especially during bouts of evolution of the disease, also, hypoxia and tumour necrosis factor alpha (TNF-) are anorexiogenic (Lamisse, 2000).
(2) Elevated resting energy requirements:
Several reports indicate that malnourished COPD patients have elevated resting energy expenditure (REE); Wilson et al. (1990) found that REE measured by indirect calorimetry was significantly higher in stable malnurished COPD patients in comparison to adequately nourished ones; and concluded that there is a hypermetabolic state in stable malnourished COPD patients which may be a factor in weight loss, and that this elevated REE needs to be taken into account when determining caloric requirements for COPD patients. Schols, et al. (1991) also found that REE measured with ventilated hood system was significantly higher in weight-losing compared to weight stable COPD patients when values were normalized for predicted metabolic rate or kilogram fat-free mass using bioelectrical impedance. Fu et al. (1998) found that REE of malnourished COPD patients was significantly higher than that of the normourished patients, elevated REE may have a significant relationship with abnormal lung function, and it may be a cause of malnutrition in clinically stable patients with pulmonary emphysema. It was also found that the total daily energy expenditure (TDE) is significantly higher in COPD patients than healthy subjects and that; the non-resting component of TDE (TDE-REE: physical activity and diet-induced thermogenesis) was significantly higher in COPD patients than healthy subjects (Baarends et al., 1997).
Many believe that weight loss in COPD is due to a state of hypermetabolism that creates a negative energy balance and, eventually, weight loss (Mannix, et al., 1999). Hypermetabolism in these patients has been shown to be the result of several factors; including:
(1) Medications, including -agonists and theophylline compounds that could stimulate metabolism (Vaisman; et al., 1987).
(2) Elevated work of breathing.
(3) Ventilatory muscle inefficiency, resulting in a greater energy demand per amount of work performed. (Donahoe, et al., 1989)
(4) Increased levels of proinflommatery cytokines (deGodoy; et al., 1996).
The role of elevated O2 cost of ventilation (O2COV) in weight loss in COPD patients is a matter of controversy, Field, et al., (1982) stated that O2 cost of breathing can increase to as much as 24% during acute respiratory failure. Also, Donahoe et al. (1989) showed that O2 cost of breathing was higher in malnourished than in normally nourished COPD patients. Mannix, et al. (1999) concluded that elevated O2COV often seen in COPD patients is a significant factor in weight loss that often accompanies this disease process; There were a series of statistically significant relationships that linked poor lung function with an increased O2COV, and increased O2COV with a state of hypermetabolism, and the hypermetabolic state with reductions in the body mass index (BMI).
On the other hand Schols, et al. (1991) stated that malnutrition correlates only weakly with the severity of respiratory dysfunction. Ryan et al. (1993), believed that it is unlikely that patients with clinically stable COPD would have suffiently increased energy expenditue attributable to the increased work of breathing or ventilatory muscle inefficiency to cause a hypermetabolic state. Hugli, et al. (1995) found that the inhibition of diaphragmatic and intercostal muscles activity during non-invasive mechanical ventilation does not normalize REE in hypermetabolic patients with COPD. It should be noted that; although increased work of breathing may contribute to increased REE; there's no convining evidence that this is the sole explanation, and other factors which could stimulate metabolism have to be considered (Schols, et al., 1996).
Also, hypermetabolism alone as a possible mechanism of weight loss in COPD patients is unlikely because the metabolic requirements reported should be easily met by increase in the dietary intake (de Godoy, et al., 1996).
It seems to be that there is a nutritionl difference between patients with emphysema and those with chronic bronchitis; Jounieaux et al. (1995) compared the oxygen cost of breasthing (VO2 resp.) in 19 patients with severe COPD intubated for acute respiratory failure. They found that; despite similar expiratory airflow obstructhion, patients with emphysema exhibited significantly higher VO2 resp. than patients with chronic bronchitis. Morever, emphysema was associated with nutritional depletion assessed through decrease in BMI. This seemed to affect somatic stores [significant decrease in arm muscular circumference and triceps skin fold thickness (TSFT)], whereas visceral stores were preserved (no decrease in serum albumin, serum prealbumin, and retinol binding protein). Malnutrition appeared to be the consequence of a hypermetabolic state of the respiratory muscles, with a significant negative correlation between VO2 resp. and BMI, arm muscular circumferences and TSFT. Total O2 consumption normalized for body surface was similar in the 2 patient groups.Thus, in emphysemtous patients, the oxygen available for tissues other than respiratory muscles was significantly reduced. This could explain nutritional differences observed between patients with emphysema and those with chronic bronchitis.
(3) A step-decline process:
Weinsier et al. (1979): stated that patients with COPD obviously entered the hospital in a malnourished state. In view of the negative effect of hospitalization on nutritual status; this would place the patients with COPD in a catastrophic position nutritionally. Wilson et al. (1985) suggested that weight loss in COPD patients occurs during periods of clinical instability; such as intercurrent infections or exacerbation of chronic airflow limitation. Donahoe and Rogers (1993); have offered their hypothesis that; a "step-decline process" where in an initial event, i.e., a COPD exacerbation, results in hypermetabolism and/or a reduced caloric intake. The subsequent weight loss is accompanied by an incomplete metabolic adaptation, so that the caloric intake may only be sufficient to maintain a new stable, but lower, weight. This process continues as additional COPD exacerbations present themselves, ultimately resulting in a body weight low enough to be classified as protein energy malnutrition.
(4) An adaptive mechanism:
Starvation studies in animals and humans suggest that weight loss may be an adaptive mechanism serving to minimize total oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (Corbett et al., 1986). In these studies, weight loss due to food restriction was accompanied by a disproportionately large reduction in REE. Ryan et al. (1993) reasoned that, a similar mechanism might be operative in malnutrition, and that during periods of clinical stability, malnounished COPD patients would have a reduced REE.
(5) Abnormal tissue oxygenation:
A hypothesis for weight loss in COPD states that tissue oxygenation may be abnormal in COPD; even in those with relatively normal arterial oxygen content (Filley, et al., 1968 and Donahoe, et al., 1992). This abnormality, along with a deficiency of high-energy phosphate molecules within the peripheral and respiratory muscles of COPD patients may interfere with the adequate delivery of nutrients, resulting in weight loss (Gertz, et al., 1977).
(6) Impaired gastrointestinal function:
Gomaa et al. (1982), demonstrated increased gastric secretion in COPD patients in response to hypoxemia and hypercapnia; an effect which might have contributed to increased incidence of peptic ulceration in this group of patients. David et al. (1985) suggested that patients with COPD are more prone to gastrointestinal disorders of non-specific nature such as abdominal bloating and blenching, it was demonstrated that some patients with severe COPD may experience significant arterial oxygen desaturation during meals. Hamed et al. (1993) found that, the frequency of gastroesophageal reflux disease (GERD) among a group of COPD patients was 55%. Reflux was more in patient with low flat diaphragm than in those with normal diaphragm. Also it was more in smokers with irreversible COPD than non smokers. It was suggested that esophageal reflux should be thought in patients with irreversible COPD and anti-reflux therapy might be expected to improve the pulmonary symptomatology in those patients. Arafa et al. (2000) reported that gastroesophegeal reflux has definitely a strong relationship with broncial hyper-reactivity.
On the other hand; Wilson et al. (1986), demonstrated normal gastrointestinal function in a group of emphysema patients and those patients were able to increase their caloric intake to levels well above their caloric needs without any manifestations of malabsroption.
(7) Role of cytokines - TNF-:
Recently, cytokine-mediated metabolic derangments have begun to be considered as among the candidates responsible for cachexia in COPD patients. Recent data have shown that a systemic inflammatory response is present in patients with COPD, based on elevated concentrations of acute phase proteins, tumour necrosis factor (TNF)- receptors and soluble adhesion molecules in the peripheral blood (Riise; et al., 1994 and Schols, et al., 1996).
A selective depletion of fat-free mass (FFM) was found in those hypermetabolic COPD patients who exhibited an acute phase response. This finding suggests that a catabolic response may be present in this subgroup of patients and is consistent with the hypothesis that; during an acute phase response; cytokines redirect host protein metabolism away from peripheral tissues such as muscle and towards the liver; and it was concluded that inflammatory mediators could be useful markers to include in the selection and follow up of interventions aimed at reversal of tissue depletion in patients with COPD (Schols, et al., 1996).
In addition, clear evidence for a relationship between weight loss and plasma TNF- has ben shown in COPD; diFrancia, et al. (1994) found that TNF- serum levels (measured by immunoradiometric assay) were significantly higher in weight-losing than weight stable COPD patients, and since renal function was in normal range; increased TNF- production; and not decreased clearance, was concluded to be a likely cause of weight loss in COPD patients. Also deGodoy, et al. (1996), demonstrated that monocytes of COPD patients with recent weight loss present elevated TNF- production, when compared with monocytes of weight-stable COPD patients and control subjects; and although no cause-effect relationship could be established in this study; these findings suggest a possible role for TNF- production as a marker of the weight-losing processes in these patients. TNF- produces a cachexia-like syndrome in animal models and has been implicated as a mediator of cachexia in several clinical conditions including cancer, chronic heart failure, cystic fibrosis, and anorexia nervosa (Balkwill, et al., 1987; Levine, et al., 1990; Schattner et al., 1990; Norman et al., 1991). In animal models, chronic exposure of the host to elevated circulating TNF- is capable of inducing a cachectic state characterized by anorexia and net catabolism of the whole body lipid and protein (Tracey, et al., 1988). The catabolic effects of TNF- on muscle remain, even when caloric needs are met by total parentral nutrition (Matsui, et al., 1993).
Studies in cancer patients and normal individuals have shown that a single injection of recombinant TNF- reproduces many of the physiologic and metabolic changes associated with the acute phase response including; fever, neuroendocrine stimulation, and increased lipid and amino acid turnover (Warren et al., 1987; Starnes et al., 1988; Poll, et al., 1991). Also, TNF- is an important mediator of the host response to infection (Tracey et al., 1988). This cytokine modulates the function of lymphocytes and polymorphs at sites of inflammation where its effects are essentially protective to the host. Increased TNF- production may enhance an injury process locally, and elevated circulating levels may have deleterious systemic effects (Schols et al., 1996).
Regarding passible explanation for the role of cytokines in cachexia of COPD patients; it was stated that; besides the fact that inflammatory cytokines may induce anoroxia such as observed in experimental studies (Fong et al., 1989); enhanced levels of acute phase proteins have been related to an increased REE in COPD (Schols, et al., 1996).
Regarding possible mechansims; by which TNF- acts; causing weight loss in COPD patients.
1-TNF- production may contribute to the alterations in systemic metabolism and protein turnover in these patients leading to progressive cachexia. Alternatively, this marker may serve to identify a second pathophysiologic process, such as allered dietary intake, which is also characteristic of malnourished patients (deGodoy; et al., 1996).
2- The physiologic relevance of the slightly but significantly increased TNF- levels in the COPD patients is difficult to explain, but several speculations warrant further discussion (Takabatake, et al., 1999). First, inflammation is not only the source of activation of the TNF- system hypoxia , for example, can induce TNF- and sTNF-R release in a human macrophage cell line (Scannell et al., 1993).
Also, Ghezzi et al., (1991) and Hempel, et al., (1996) found that hypoxia has a potentiating effect on the in-vitro production of inflammatory cytokines (IL-1 and TNF-) after endotoxin stimulation that was postulated to be due to a decreased antiinflammatory prostaglandin PGE2 synthesis. Second, although TNF- exerts its effect at least partly in a paracrine/autocrine fashion in each tissue, there is no significant correlation between TNF- levels at local sites and in the systemic circulation (Torre-Amione, et al., 1995). It may be passible that circulating TNF- is spilled from the lung tissue of COPD patients (Rich, et al. 1989 and Nakamura et al., 1996). Third, it was reported that circulating TNF-, sTNF-R55 and sTNF-R75 were increased in patients with congestive heart failure (Nozaki et al., 1997) to levels similar to those observed in our COPD patients, Since the levels of both sTNF-R55 and sTNF-R75 were affected in close proportion to the disease severity and hemodynamic variables in patients with congestive heart failure, the increased levels of circulating TNF- and sTNF-Rs found in this study would be related to the pathophysiology of right-sided heart failure associated with COPD.
However, further studies examining the relationship between energy intake, TNF- production, and body composition in weight-losing COPD patients are indicated.
It should be noted that TNF- has important relationships to different parameters related to the weight loss process in COPD patients;
It was found that serum TNF- levels in patients with COPD were significantly correlated with fat mass and no association was observed between lean mass and serum TNF- levels, and it was concluded that TNF- may cause a decreases in fat mass in patients with COPD (Yamamoto, et al., 1997).
Non-malnourished, clinically stable, non-severely hypoxic COPD patients display an increased REE that is related with plasma TNF- concentration (without apparent systemic inflammation) and to theophylline treatment, but that is independent of parameters of respiratory function (Nguyen, et al., 1999).
It was found that, the presence of potentially pathogenic micro-organisms (PPMs) was significantly associated with higher percentages of neutrophils and TNF- concentration in the bronchoalveolar lavage (BAL) of COPD patients .
As prescribed previously; systemic hypoxemia noted in patients with COPD is associated with activation of the TNF- system in vivo, which may be a factor contributing to weight loss in COPD patients.
(Takabatake, et al., 2000).
(8) Role of leptin:
Leptin, an adipocyte-derived hormone, plays an important role in energy haemostasis by signaling the brain about the amount of adipose tissue stored in the body (Flier, et al., 1997 and Auwerx et al., 1998). After interaction with specific receptors located in the CNS and in peripheral tissues, leptin induces a complex response, including control of body weight and energy expenditure (Tartaglia, et al., 1997).
Improvements in lipid metabolism and glucose haemostasis, and increased thermogenesis, are considered to be some of the important metabolic effects of leptin. Administration of recombinant leptin to oblob mice, which have a genetic defect in leptin production, decreases food intake, increases energy expenditure and decreases bady weight (Flier, et al., 1997 and Auwerx et al., 1998). Circulating leptin levels are reported to correlate with the body mass index (BMI) in humans. (Maffei, et al., 1995, and Considine, et al., 1996)
Tokabatake et al., 1999; found that serum leptin levels in COPD patients were not elevated over those in healthy controls; although serum TNF- levels were significantly increased in COPD patients. Furthermore , they were unable to find any relationship between circulating leptin and TNF- levels. These observations suggested that leptin is not primarily under the control of the TNF- system, and it seems not to play an important role in weight loss in COPD patients. The positive correlation between serum leptin levels and body mass index in patients with COPD confirms that circulating leptin levels remain regulated even in patients in the cachectic status seen in COPD.
Schols et al. (1999) found that emphysematous patients were characterized by a lower BMI due to a lower fat mass (FM) and by lower mean (detectable) leptin concentrations compared with bronchitic patients. Furthermore, a significant partial correlation coefficient between leptin and sTNF-R55 adjusted for FM and oral corticosteroid use was seen in emphysema but not in chronic bronchitis. Also, in predominantly emphysematous depleted female patients with COPD, baseline plasma leptin divided by FM was in addition logarithmitically inversly related to baseline dietary intake and to the degree of weight change after 8 weeks of nutritional support. They concluded that this proposed cytokine-leptin link in pulmonary cachexia may explain the poor response to nutritional support in some of the cachectic patients with COPD and may open a novel approach in combating this significant morbidity in COPD.
Openbrier, et al. (1984) demonstrated that psychosocial factors have been explored by several investigators and found not to be substantially different between nourished and malnourished patients with COPD.
Field, et al. (1984) stated that factors related to increased energy consumption relative to the work output may contribute; these factors include respiratory muscle parameters (such as variation in coupling between different muscles, the amounts of isometric contraction, the pattern of contraction, the use of accessory muscles as fixators of the rib cage, the work by the diaphragm on the abdomen, and the amount of respiratory muscle blood flow). Also, the work consumed by chest wall distortion (ribcage-abdomen partitioning) may contribute.
Adverse effects of malnutrition on respiratory function include:
(1) Decreased respiratory muscle strength.
(2) Altered ventilatory drive.
and (3) Impaired immunologic function
(1) Effects of malnutrition on respiratory muscles in COPD:
Thurlbeck (1978), found in an autopsy study that the diaphragmatic weight of patients with pathologic evidence of emphysema was decreased and the decrease was out of proportion to the reduction in body weight. Likewise, Campbell et al. (1980) found a decrease in the size of fibers in the external intercostal muscles of patients with COPD. Both diaphragmatic muscle weight and sternocleidomastoid muscle thickness were reduced in underweight as compared to normal weight patients with COPD (Arora and Rochester, 1982).
In COPD; inspiratory muscle weakness must be severe for hypercapnia to occur. In patients with myopathy, hypercapnia occurs when inspiratory pressures are less than one-third of normal. However, hypercapnia is found in the majority of patients with COPD when inspiratory pressures are only less than one-half of normal (Rochester; et al., 1985).
Chronic airflow limitation leads to a marked increase in the flow resistive work of breathing and to hyper inflation . The latter causes further demands to be placed on inspiratory muscles as a result of a marked decrease in the ability to inflate the rib cage because two of the muscle groups which do so at normal lung volumes become ineffective, (Diaphragm and rib cage muscles). Furthermore, hyperinflation decreases inspiratory muscle strength and efficiency by placing the respiratory muscles on an inefficient part of their length-tension curve. The resultant increased work, but decreased strength and mechanical effectiveness, of the inspiratory muscles puts them at risk of developing fatigue. Fatigue is potentially aggravated by malnutrition because of decrease in diaphragmatic mass, strength, endurance, and perhaps, energy stores per contractile unit of muscle (Edelman et al., 1986). Also; Rochester et al. (1986) stated that COPD increases the lung volume and airway resistance, thereby increasing the work of breathing and placing the inspiratory muscles at a mechanical disadvantage. Nutritional and metabolic events further compromise respiratory muscle function and affect the expiratory as well as the inspiratory muscles. In addition to reduced muscle mass and hyperinflation; a number of other nutritional factors can alter the diaphrogmatic strength in patients with COPD as well as other respiratory diseases, mineral and electrolyte defiencies impair respiratory muscle function, Aubier, et al. (1985) demonstrated that hypophosphatemia decreases the diaphragmatic contractile strength; as measured by transdiaphragmatic pressures in mechanically ventilated patients with acute respiratory failure. Hypocalcemia and hypomagnesemia are also associated with reduced diaphragmatic function. Fiaccadori et al., (1994) found that muscle phosphorus content of both respiratory and peripheral muscles was significantly reduced in COPD patients; and that phophorus depletion could depend, at least in part, on malnutrition and a condition of renal phosphorus wasting possibly linked to some drugs commonly used in patients with COPD (xanthine derivatives, diuretics, etc).
Malnutrition may further compromise already reduced lung function; dyspnea may worsen in the spontaneously breathing patients with COPD and hypercapnic respiratory failure may be precipitated and weaning from mechanical ventilation made more difficult in the malnourished patients with COPD compared with the normally nourished patients with COPD (Pingleton, 1998).
(2) Altered ventilatory drive:
Malnutrition also affects ventilatory drive. The interaction of nutrition and ventilatory drive appears to be a direct function of the influence of nutrtion on metabolic rate. In general, conditions that reduce metabolic rate reduce ventilatery drive. A decrease in metabolic rate occurs with staruation (Pingleton et al., 1998).
A parallel fall in metabolic rate and hypoxic ventilatory response has been documented in humans . A 58 percent reduction in the ventilatory response to hypoxia was found in volunteers placed on a balanced diet of 550 kcal per day for 10 days. The ventilatory response returned to normal with refeeding (Askanazi et al., 1980).
Ventilatory response is also affected by dietary constituents. After a 7 days, protein-free diet, a blunted ventilatory response to carbon dioxide has been observed (Askanazi et al., 1984).
Some conditions can predispose to ventilatory failure; as COPD; by increasing the work of breathing. Specific reasons for muscle weakness include critical illness (electrolyte imbalance, acidemia, shock, sepsis), chronic illness (poor nutrition, cachexia), and neuromuscular diseases. Inspiratory muscle weakness from mechanical disadvantage to the diaphragm is characteristic for asthma and COPD. Acute treatment of respiratory muscle failure involves respiratory muscle rest through mechanical ventilation and removal of noxious influences (infection, metabolic disarray), whereas chronic treatment involves rebuilding the contractile apparatus by nutritional repletion and training (Rochester, et al., 1993).
Consequences of decreased respiratory strength and decreased ventilatory drive may include impaired cough and, hence, increased risk for atelectasis and pneumonia in spontaneously breathing patients with respiratory disease. Decreased respiratory muscle strength and drive may also prolong the duration of mechanical ventilation in patients who, otherwise, are candidates for weaning. Thus, the potential for adverse outcome is present in patients who are malnourished from their disease, as well as in patients with respiratory disease who develop malnutrition as a consequence of other intercurrent diseases (Pingleton, 1998).
(3) Malnutrition and immunity:
Hunter, et al. (1981) stated that; because malnutrition is associated with loss of humoral and cell-mediated immunity; an acquired immune deficiency in malnourished patients with COPD may exist and partly explain the increased premorbid susceptibility to infections in these patients. Also thay stated that relative and absolute skin test anergy have been reported in patients with COPD and weight loss.
Although normal total lymphocyte counts are characteristic for patients with stable COPD; lymphopenia may exist after weight loss is noted. And; perhaps; lymphopenia exists in the settings of severe illness or acute respiratory failure; but not in patients with COPD slowly-losing weight (Openbrier, et al., 1983).
Edelman et al. (1986), had studied major lung defense systems in relation to nutrition; antioxidant defense system, surfactant production and immunologic competence;
(1) Antioxidant defense system: It was clear that nutritional deficiencies may impair antioxidant protective mechanisms; such deficiencies include lack of sulfur-containing amino acids, copper, selenium, iron, vitamins (-dl tocopherol, carotenes and ascorbic acid), degree of fatty acid saturation in lipids, and caloric intake.
(2) Surfactant production: it was recommended that greater clinical priority should be given to nutrition as a vigorous part of total support in premature infants; as it was found that prenatal (intrauterine) nutritional deprivation can exert a deterimental effect on the oxygen tolerance of the newborn.
(3) Immunologic competence: It was stated that;
Nutrition is an important factor to the immunologic and, most likely, other defenses of the lungs.
The main aspects of immunity that are impaired in protein-caloric malnutrition (PCM) include; cell-mediated immunity, secretory IgA, antibody response, the complement system, and bactericidal capacity of neutrophils.
- The respiratory mucosa provides a surface that is constantly exposed to a variety of contaminants, pathogens and sensitizing substances, which, by a variety of defense mechanisms, are prevented from entering into the lung tissue or systemic sites.
- Recent data indicate that nutritional deficiency is associated with increased number of lymphatic cells in alveolar bronchial washings, reduction of T-helper to T-suppressor cell ratio, reduction of ciliary movement and increased bacterial adherence to epithelial cells.
- Deficencies of individual nutrients such as vitamin A, pyridoxine, zinc and others can also impair immunocompetence and leads to increased vulnerability to infection.
Mohsenin et al. (1989) found that; malnutrition has profound effects on cell-mediated immune response and humoral immuity with reduced levels of secretory IgA. In patients with COPD, colonization of respiratory tract bears a direct relationship with parameters of nutritional status; Patients with significant nutritional impairment have more tracheal cell bacteria adhered to and the tracheas were more frequently colonized by psudomonas species. The improvement of nutrition in these patients resulted in less bacterial cell binding to tracheal epithelial cells, it was found that refeeding and weight gain were associated with a significant increase in the absolute lymphocytic count and improvements in skin test anergy after 21 days of refeeding; in nine patients with advanced COPD and recent weight loss (Fuenzalida, et al., 1990).
Protein caloric malnutrition is one of the most frequent causes of acquired immunodeficiency in humans. Chemotaxis and opsonic function and phagocytic function usually remain normal or are mildly depressed, and intracellular killing is decreased. The thymus, spleen, and lymph nodes become markedly atrophic, and lymphocyte numbers may decrease. Although immunoglobulin levels remain normal or are slightly increased, antibody responses may be depressed. Consequences of altered immune function may include increased respiratory infections, such as pneumonia (Pingleton, 1998).
Delayed type of hypersensitivity (DTH) tests were used to evaluate the nutritional and immune status in a group of COPD patients and to predict outcome in various conditions; it was found that; patients with COPD in stable condition have diminished DTHs and late allergic reaction (LARs); and that magnitude of the LAR may be a prognostic marker in patients with COPD (Dahlen, et al., 1999).
Malnutrition and clinical course of the disease:
Malnutrition in COPD patients has a considerable impact on both morbidity and mortality; as evidenced by reports of increased frequency of hospitilization, corpulmonale, heart failure and increased mortality (Hoch, et al., 1984). Elders with chronic airflow limitation who are undernourished are at risk for a variety of complications, including atelectasis, pneumonia, respiratory muscle deficiencies , hypoxemia, and even respiratory failure (DeLetter, et al., 1991). Malnutrtion may contribute to the onset of acute respiratory failure, it limits the ability to produce surfactant, leads to reduced protein synthesis, reduces cell mediated immune responses raising the patient's susceptibility to lung infection and affects the functiong of peripheral and respiratory muscles (Pezza, et al., 1994). An acute exacerbation of COPD is accompanied by an impaired energy balance due to a decreased dietary intake and an increased resting energy expenditure (Vermeeren, et al., 1997).
Pingleton (1998) noted that consequences of reduced respiratory muscle strength and reduced ventilatory drive in malnourished COPD patients may include: impaired cough raising the risk of atelectasis and pneumina in spontaneously breathing patients and prolonged duration of mechanical ventitation in patients who, otherwise, are candidates for weaning. Also malnutrition may further compromise already reduced lung function: dyspnea may worsen in the spontaneously breathing patients with COPD and hypercapnic respiratory failure may be precipitated and weaning from mechanical ventilation made more difficult in malnourished patients with COPD compared with the normally nourished patients with COPD.
Malnutrition and Respiratory failure in COPD patients:
Driver and LeBrun (1980); stated that malnutrition is a relatively common problem in critically ill patients who are being mechanically ventilated. Drivers et al. (1982) had observed more severe nutritional depletion in patients with respiratory failure than other COPD patients. It's unknown if these nutritional changes result from or contribute to the poor clinical status. Pingleton and Eulberg (1983), stated that critically ill patients require many modalities of supportive care; nutrition is an important therapeutic modality in the critically ill patients with acute respiratory failure from primary lung disease.
In malnourished patients responding to nutritional therapy with a rise in serum albumin levels and diuresis of expanded extracellular fluid compartment, mortality in the form of length of hospitilization and postoperative complications is decreased (Askanazi et al., 1986). It was noted that nutritional impairment can alter cellular resistance of the tracheobronchial mucosa to bacterial cells which can not only precipitate respiratory failure especially in patients with underlying primary lung disease, but also can delay recovery from this critical situation (Pingleton and Harmon, 1987). Also, it was noted that malnutrition was more frequent in those COPD patients who required mechanical ventilation than in those who did not; and it was suggested that malnutrition may have deleterious effects on weaning off mechanical ventilation (Laaban et al., 1993).
Malnutrition and Mortality in COPD patients:
Weight loss has long been known to be associated with increased mortality rates (Vanderberg and Colleagues, 1967).
Wilson and coworkers (1989) reported that the survival experience of male patients with COPD without hypoxemia and found body weight to be a significant predictor of survival after controlling for FEV1, total lung capacity, exercise capacity, and resting heart rate .
In a study of 348 patients with severe COPD, it was found that low BMI was a strong predictor of death from respiratory causes after adjustment for age, gender, current smoking status, FEV1, and use of home oxygen; although BMI was not found to be a significant predictor of all-cause mortality in a subgroup of non hospitilized patients, probably because of a small sample size (Gray-Donald, et al., 1996). When adjusted for age, gender, pulmonary functions, arterial blood gases, hematocrite, use of steroids, and use of oxygen; BMI was a significant predictor of survival in 135 nonsmoking patients with severe COPD and moderate hypoxemia. (Gorecka and Caleagues, 1997).
Schols et al. (1998) provided furthermore evidence to support the hypothesis that body weight (BW) has an independent effect on survival in COPD, and morever; the negative effect of low BW can be reversed by appropriate therapy. Irrespective of stage of the disease; underweight is an important independant risk factor for mortality. In mild to moderate COPD; the best prognosis is found in normal-weight or overweight subjects, whereas in severe COPD overweight and even obesity is associated with a better survival (Landbo, et al., 1999).
The role of low BMI as a determinant of poor survival in COPD patients could have been due to several factors; such as impaired immune response (Hunter, et al., 1981), impaired gas exchange (Braun; 1984 and Schols; 1989) and respiratory muscle weakness (Donahoe; et al., 1989); all of which have been related to malnutrition in COPD patients. It is still possible; however, that the decline in BMI in patients with COPD is a marker of advanced disease; corresponding to a carrently unknown factor or factors that are also responsible for the decline in pulmonary function and progression of the disease (Landbo; et al., 1999).
Other risk factors for mortality in COPD patients include diffusing capacity for carbon monoxide (B oushy, et al., 1973), cor pulmonale (Traver et al., 1979), age (Anthonisen et al., 1986), form of COPD, asthmatic or not, (Burrows et al., 1987), smoking behaviour (Postma et al., 1989), hypoxemia (MacNee, 1992) and hypercapnia (Boushy et al., 1973 and MacNee, 1992).
Nutritional assessment is the integration and interpretation of anthropometric, biochemical, clinical, and dietary data to determine the nutritional and health status of individuals and population groups (Kuezmarski, et al., 1993). The objectives of clinical nutritional assessment are: to (1) identify individuals who will benifit from nutrition support therapies, (2) determine baseline values by which to measure the effictiveness of nutritional intervention, and (3) detect and treat vitamin and mineral deficiencies (Veldee et al., 1994).
Nutritional assessment includes the following:
(1) Nutritional history.
(2) Physical examination.
and (3) Some physical and biochemical measurements.
(Veldee et al., 1994).
I- Nutritional history:
The history should include specific questions concerning usual body weight, recent weight changes, dietary habits (including frequency and amount of alcohol ingestion), appetite, gastrointestinal function, the use of vitamin /mineral supplements, and the use of drugs that might interfere with nutrient absorption or utilization. A complete history can determine a patient's risk of caloric, protein, vitamin, or mineral deficency (Veldee et al., 1994).
II- Physical examination:
The physical examination looks for overt symptoms of nutrient deficiencies. Overt symptoms characteristic of a single-nutrient deficency, however, are rarely seen. More common, is the general appearance of poor health and subcutaneous fat and muscle wasting (Veldee et al., 1994).
III- Physical and biochemical measurements:
The following are some physical and biochemical measurements that are used in evaluating protein-energy malnutrition.
(A) Measurements of body Composition:
Body composition can be described in either chemical or anatomical terms (Veldee et al., 1994). This figure illustrates the composition of a hypothetical 70 kg adult man in both chemical and anatomical units. Values vary from one individnal to another.
Body composition can be measured indirectly in many ways that differ in case of determination, accuracy, total cost, and thus applicability to the clinical setting.
At present, in-hospital body composition measures are limited to anthropometric measurements, quantitation of urine 3-methylhistidine, bioelectric impedance analysis, isotope dilution studies, and infrared interactance. Research methods with potential for future clinical application include ultrasound, computed tomography (CT), neutron activation analysis, magnetic resonance imaging, and single or dual photon absorptiometry (Lukaski, 1987).
 Anthropometric measurements:
Anthropometric measurements are particularly useful in detecting moderate and severe degrees of malnutrition, notably imbalances of protein and energy (Kuezmarski, et al., 1996). They include the following:
(1) Body weight:
Body weight is a simple, noninvasive predictor of body fat and caloric balance. A patient's actual (current) weight is commonly compared with the reported usual weight or "ideal" weight obtained from standard tables. The most commonly used tables are published by the Metropolitan Life Insurance Company and represent the range of weight for a given height associated with longevity . The rate of weight loss also is an important factor in determing the extent of nutritional depletion (Veldee, et al., 1994)
This table lists weight criteria commonly used to deterine nutritional risk:
Table (1): Weight Criteria used to determine nutritional risk
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* Per cent weight loss is calculated using usual body weight (UBW) and current body weight (CBW): % loss= [(UBW-CBW)/UBW] x 100.
(Cited from Veldee, 1994)
As regards COPD patients:
Schols and celleagues (1993) reported that; a substantial number of normal weight patients with COPD with abundant fat mass have a depletion of fat-free mass.
Also, Saudny-Unterberger, et al. (1997) stated that changes in body weight as a measure of change in nutritional status in acute exacerbations of COPD is not very useful; as fluid balance is often disturbed, small changes in weight may be the result of either fluid retention or fluid loss complicated by steroid treatment.
Limitation: Unfortunately, edema or severe dehydration can distort actual body weight measurements and lead to misinterpretation of relative weight for height values and weight changes (Pingleton et al., 1998).
In contrast to the difficulties of evaluating changes in body weight in this population, short-term changes in body protein (which is more important) can be estimated using nitrogen balance (Mackenzie, et al., 1985).
Wilson et al. (1989) studied the relationship between body weight and some pulmonary functions and survival in a group of COPD patients. They found that body weight (expressed as a percent of the ideal (% IBW) was directely related to FEV, and inversly related to % TLC, after adjusting for FEV1. It was a powerful positive correlate with exercise capacity; afte adjusting for FEV1. Also it was a powerful predicter of diffusing capacity in patients with the same FEV1. Mortality appeared to be influenced by body weight , independent of FEV1.
(2) Body mass index (BMI):
Assessment of BMI (weight in Kg divided by height in m2) has the advandage of simplicity and is useful for assessing both over-and under nutrition. A normal BMI is defined as 18.5 to 24.9 Kg/m2. Overweight is a BMI of 25.0 to 29.9 kg/m2, obesity is a BMI of 30.0 to 39.9 kg/m2, and morbid obesity is a BMI >40 kg/m2. Conversly, the risk for protein-energy malnutrition can be graded as mild: BMI = 17.0 to 18.4 kg/m2; moderate: BMI = 16.0 to 16.9 kg/m2, and severe : BMI < 16.0 kg/m2. BMI of 13 to 15 kg/m2 suggests that the total body fat content is less than 5 percent of weight (Denke and Wilson, 1998).
Sahebjami et al. (1993) studied the prevalence of abnormalities in the nutritional status, and their correlation with pulmonary function tests , in a group of outpatients with stable COPD. They concluded that; BMI is simple and accurate indicator of nutritional status in these patients; A significant and positive correlation was found between BMI as the independent variable and diffusing capacity for carbon monoxide (DLCO), FEV1 and its ratio to FVC. Also, a significant and negative correlation existed between BMI and RV and its ratio to TLC. Also, Pascual et al., (1996) found that BMI is the nutritional value that better predicts the FEV1% in outpatients with stable and severe COPD.
Limitation: The BMI is simple and is a widely used means of estimating energy balance, but it does not take into account differences in frame size (Denke and Wilson, 1998).
(3) Skin-fold thickness:
Because more than half of the total body fat is subcutaneous, measurement of skin-fold thickness provides a noninvasive index of body fatness. The sum of skin-fold measurements taken from several body sites can be used to estimate percent of total body fat (Durnin, et al., 1974). The skin and adjacent subcutaneous tissue are grasped between the thumb and forefinger, gently shaken to include underlying muscle, and pulled away from the body to allow the jaws of the caliper to spinge upon the skin. Measurements are read after allowing tissue compression and are repeated at least three times (Veldee, 1994). The triceps skinfold thickness is measured on the back of the mid-upper arm over the triceps muscle. A calibrated skinfold caliper such as the lange, Harpenden, or Holtain should be used for the measurement. The triceps skin thickness differs with frame size and height (Denke and Wilson, 1998). The precision of skin-fold measurements depends on the skill of the anthropometrist, size of subcutaneous fat mass, and the site measured. An experienced individual can attain a precision within 5% Errors in predicting densitometrically determined body fat mass from anthropometry are between 3 and 9% (Veldee, 1994).
Limitation: Skin-fold measurements are relatively insensitive to acute changes in nutritional status and, therefore, are of limited use as a monitoring tool in the acute care setting. Also, Clinical judegment must be used in cases with edema or skewed patterns of body fat distribution (Veldee, 1994).
More direct techniques to measure percent body fat such as underwater weighing, x-ray absorptionometry, and nuclear magnetic resonance imaging can also be employed under some circumstances (Denke and Wilson, 1998).
(4) Circumference measurements:
The mid-arm circumference (MAC) and triceps skin-fold (TSF) thickness can be used to calculate the mid-arm muscle area (MAMA) and thereby provide an index of lean body mass. MAMA is calculated using the following fromulas; (Heymsfield, et al., 1982). (all the measures are in centimeters)
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This assessment is a valuable means of identifying protein malnutrition, a particular problem in the elderly: (Denke and Wilson, 1998). However, the above formulas have been shown to over estimate the MAMA by 20 to 25% in comparison with computerized tomography (CT); owing to the inclusion of bone in the calculation of the MAMA by the arthopometric method.
A close correlation exists between 24.h urinary creatinine (a measurement of total body muscle mass and the MAMA. An adult MAMA < 4 cm2 has been associated with eventual death values between 9 and 14 cm2 are considered indicative of severe protein-energy malnutrition (Chiba, et al., 1989).
 Urinary creatinine and creatinine/height index:
Creatinine is a normal waste product of muscle energy metabolism formed by the nonenzymatic hydrolysis of free creatine librated during the dephosphorylation of creatine-phosphate. Twenty-four hours urinary creatinine excretion correlates well with total body mescle mass in individuals with normal renal function, sufficient food intake, and a diet of constant composition (LBM can be estimated: LBM (kg)= 7.138 + 0.02908 + urine creatinine (mg) (Margo; 1998). Creatinine excretion declines with age and is increased by acute infection, injury, severe emotional stress, vigorous exercise, and diet high in protein, creatine, and creatinine (Heymsfield et al., 1983 and Lukaski et al., 1987).
The creatinine/height index (CHI), relates the 24-hours creatinine excretion in an individual (patient) to published values for a normal healthy adult (control) of the same sex, age and height (Bistrian et al., 1974).
Abbildung in dieser leseprobe nicht enthalten
Creatinine height index value of 60-80% indicates mild somatic protein depletion, 40-60% moderate, and less than 40% severe (Blackburn and Thorton, 1979).
Limitations: Certain requirements, such as the need for a 24-hs and perferably 72 hours urine collection limits its practicality (Veteri and Alvarado, 1970). Also, the creatinine height standards are based on a small number of individuals. Furthermore, the CHI assumes that kidney function is normal, which is often not the case among hospitalized patients (Gray and Gray, 1980).
Table ( 2 ): Ideal Urinary creatinine values:
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* Creatinine coefficient (men) = 23 mg/g of ideal body weight.
Creatinine coefficient (women) * 18 18 mg/kg of ideal body weight.
From Blackburn G.L., Bistrian B.R., Maini B.S., Schlamm H.T., Smith M.F.: Nutritional and metabolic assessment of the hospitalized patient J.P.E.N. 1977; 1: 11.
 Endogenous 3-Methyl Histidine excretion:
The measurement of 3-methyl histidine (3-MH) excretion (or formation) has been suggested as a simple test to estimate skeletal muscle mass. Post-translational methylation of specific histidine residues in muscle fiber actin and in white muscle fiber myosin produces 3-M.H. As a consequence of normal myofibrillar protein turnover, 3 MH is released and subsequently excreted in the urine in amounts proportional to total body skeletal muscle mass as determined by densitometry and indirect measurements of total body nitrogen and potassium. The 3-MH exeretion test has been shown to predict the Lean Body Mass (LBM) with an error of approximately 4 kg over a range of 50 to 82 kg versus an approximately 5-kg error by creatinine excretion (Lukaski, et al., 1987).
Limitation: Use of 3 MH excretion to predict skeletal muscle mass in acute care setting is limited by several factors; conditions of sepsis, trauma, steroid administration, or starvation, as those, can accelerate protein degradation and thereby disproportionally increase 3 MH excretion (Lowry, et al., 1985).
 Bioelectric Impedance Analysis: (BIA)
Determination of body composition by fixed-frequency BIA delineates the human bady into two major compartments; fat and fat-free mass (FFM). FFM can be further divided into body cell mass (BCM) and extracellular mass (ECM). Although this characterisation is simplistic, it provides a working model of body composition for BIA. BCM is defined as the total mass of functioning work-performing cells of the body whereas ECM reflects the constituents involved in transport and support, such as extracellular fluids and skeleton. The balance between these two body compartments may be represented by: (Na)e- (K)e ratio (ratio of exchangeable sodium to potassuim) determined by multiple-isotope dilution (Shizgal, 1985 and Tellado-Radriguez, 1987). In normal individuals, ECM and BCM are almost equal in size, leading to an averge (Na)e - (K)e ratio of 0.98 +/- 0.02 (Forse and Shizgal, 1980). BIA relies on the conduction of a low-voltage current through electrolyte-containing fluids of the body. Resistance to current flow is the measured voltage drop and can be used directly to calculate lean bady mass (LBM). Reactance, or capacitative resistance, represents the component of current stored in cell walls. Determination of reactance is important for estimating the relative proportion of extracellular versus intracellular mass (BCM). Application of relationships derived in hospitilized medical and surgical patients, validated by isotope-dilution techniques , can thus be used to estimate BCM and ECM (Robert, et al., 1993).
Whole-body electric impedance (Z) is related to whole-body electric resistance (R) and whole-body reactance (Xc) by the following: Z2 = R2 + Xc2 (Shizgal, et al., 1990).
 Isotope Dilution:
Isotopically labelled water [deuterium, tritrium, or oxygen (18O)], sodium (22Na), and potassium (42K) can be used to quantitate body compartments by isotope dilution in both healthy and sick individuals. The principle of this method is based on the anhydrous nature of body fat and assumes that isotopes will distribute and exchange proportionally. Thus, the equilibrium concentration of deutrium, tritrium, or 18O 22Na, and 42K in a blood sample is proportional to total body water, sodium, or potassium respectively (after correcting for urinary loss of tracer) (Veldee, 1994).
Malnutrition results in a decrease in the BCM and expansion of the ECM. This is reflected in an increase in the ratio Nae/Ke. Shizgal, et al. (1987) had defined malnutrition as a Nae/Ke ratio greater than 1.22. This ratio has also been shown to be superior to a variety of nutrition indicators, including serum albumin, transferrin , percentage of recent weight loss, and triceps skin-fold thickness, in predicting mortality in a high-risk group (Tellado-Rodriguez, et al., 1987).
 Infra-red Interactance:
It's based on that; the absorptive, reflective, or transmissive properties of a tissue exposed to near-infrared radiation (700-1100 nm) depend on the tissue's chemical composition. Therefore, these properties can be used to evaluate body composition. Infrared interactance has three important advantages for application in the clinical setting; safety, portability and low cost (Veldee et al., 1994).
(B) Biochemical measurements:
Biochemical markers can identify when anablism has been induced prior to measureable improvements in body composition. The ideal biochemical protein-energy markers should have a short biological half-life, exist primarily within an accessible body fluid, have limited homeostatic controls and a constant catabolic rate, and be unaffected by vitamin or mineral status or pathophysiological states. The most common biochemical protein-energy indices are serum proteins and urinary nitrogen excretion (Veldee; 1994).
(I) Plasma proteins:
Several plasma proteins of hepatic origin have been suggested to be good dynamic indices of nutritional status. During periods of inadquate dietary protein or energy, a reduction in hepatic synthesis and secretion of these proteins causes plasma levels to fall. Reinstitution of an adequate diet induces protein synthesis, returning plasma concentrations to normal. The rate of change in protein's plasma concentration in response to nutritional inadequacy depends on the protein's biological half-life. An imbalance between the rate of symthesis or secretion and catabolism of a plasma protein will be apparent earlier in proteins with short biological half-lives (Veldee, 1994).
The following table shows serum proteins commonly used to monitor nutritional therapy:
Table (3): Sensitivity, specificity and predictive value of weekly rise in plasma protein levels in detecting positive nitrogen balance patients receiving 2 weeks of TPN (Church and Hill, 1987).
Abbildung in dieser leseprobe nicht enthalten
Limitation: Several factors can affect the serum concentration of these proteins including fluid status, hepatic function, and abnormal losses via the gastrointestinal tract or kidneys. It also must be emphasized that the liver reprioritizes protein synthesis in response to stress by decreasing production of these normal constitutive proteins so as to produce more acute phase proteins . Also, affection by aging, steroids, and chronic infection; lessen the usefulness of plasma proleins as a nutritional assessment tool (Donahoe, 1997).
Albumin is the major protein of human plasma, has a MW of 64.000, and makes up to 60% of the total plasma protein, 40% of albumin is present in the plasma, and the other 60% is present in the extracellular space. The liver produces about 12 gm of albumin per day. Prolonged, uncomplicated protein deficiency will cause albumin concentrations to fall; and values defining mild, moderate, and severe depletion are usually 28 to 35, 21 to 27, and less than 21 gm/L, respectively. Many surveys have found hypoalbuminemia to be an accurate prognostic indicator of increased morbidity, mortality, and increased length of stay among hospitilized patients (Mullen, et al., 1979; Apelgren, et al., 1982; Pettigrew, et al., 1986 and Velanovich, 1991).
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