scholarly journals Reasons why hypoalbuminaemia may or may not appear in protein-energy malnutrition

1977 ◽  
Vol 38 (1) ◽  
pp. 115-126 ◽  
Author(s):  
W. A. Coward ◽  
R. G. Whitehead ◽  
P. G. Lunn

1.Investigations have been carried out in experimentally-malnourished rats in an attempt to explain the reasons for the development of the two main forms of protein-energy malnutrition in children, kwashiorkor and marasmus.2.Isoenergetic diets with values for protein: energy (P:E) of 0.21 (control diet; C) 0.032 (low-protein diet; LP) and 0.005 (very-low-protein diet; VLP) were fed to groups of twenty-six rats either ad lib. or in restricted amounts from 5 weeks of age. Rats were killed at the start of the experiment and 1, 2 and 3 or 4 weeks later. Estimations were made of plasma albumin, insulin, corticosterone and amino acid concentrations and of the total protein content of the gastrocnemius muscles and liver.3.Rats given diet LP ad lib. gained weight slowly and by week 1 plasma albumin concentration was slightly reduced. Rats given diet VLP ad lib. gradually lost weight and plasma albumin concentrations decreased continuously.4.In contrast the major effect of dietary restriction during the first 2 weeks of the experiment was to maintain plasma albumin concentrations at normal values, irrespective of the diet given.5.At later stages, however, when the ‘restricted’ animals had become very severely wasted, albumin concentrations decreased rapidly to values approaching those found in rats given diet VLP ad lib.6.When diets LP and VLP were given ad lib. body protein was proportionally distributed in favour of muscle rather than liver. For ‘restricted’ rats the reverse was true, at least up to the time when plasma albumin concentration began to decrease.7.Plasma corticosterone concentrations increased and insulin concentrations decreased when diets LP and VLP were fed in both an ad lib. and a ‘restricted’ regimen but the effects were significantly greater in the latter situation.8.Ad lib. feeding of diets LP and VLP produced a distorted plasma amino acid pattern resembling that of kwashiorkor, but although dietary restriction resulted in a decrease in total amino acid concentration, the plasma concentration ratio, non-essential amino acids:essential amino acids was virtually unaffected.9.It was concluded that whilst the lower the protein concentration in the diet the greater is the extent of hypoalbuminaemia which develops, dietary restriction with an increase in plasma glucocorticoid concentration and body-wasting can initially delay the development of the hypoalbuminaemia. However, in the final stages of wasting which ensue, low plasma albumin concentrations can appear because of a failure of the mechanisms which had earlier been able to preserve them at normal levels. It is possible that these two separate and distinct routes to hypoalbuminaemia observed in this study may have parallels in human situations in developing countries.

1986 ◽  
Vol 70 (5) ◽  
pp. 469-475 ◽  
Author(s):  
P. G. Lunn ◽  
C. A. Northrop ◽  
R. H. Behrens ◽  
J. Martin ◽  
M. Wainwright

1. Alterations in plasma albumin concentration and gastrointestinal permeability have been investigated in rats infected with the nematode Nippostrongylus brasiliensis and fed adequate or low protein diets. 2. Infection caused only minor changes in growth and food consumption of well nourished rats but resulted in significant reductions in those fed the low protein diet. 3. Animals in both dietary groups were able to mount an immune response beyond day 10 postinfection (p.i.) which caused expulsion of the parasites, but this was less effective in rats fed the low protein food. 4. Uninfected rats fed the low protein diet had significantly lower plasma albumin concentrations than their well nourished counterparts. Animals of both dietary groups showed a progressive reduction in plasma albumin concentration as the infection developed but values returned towards normal as the parasites were expelled. 5. The reduction in plasma albumin concentration was closely associated with increases in gastrointestinal leakage of plasma protein but losses were far greater in the protein deficiency animals. Beyond day 10 p.i. protein loss decreased in both dietary groups and by day 21 p.i. had returned to normal in well nourished animals but not those fed the low protein diet. 6. Intestinal permeability measured by the lactulose:mannitol ratio technique gave similar results to the protein loss data. Permeability increased as the infection progressed then fell as the worms were expelled but remained above control values in infected protein deficient animals. 7. Overall, animals fed the low protein diet were more severely affected by the parasite than were their well fed counterparts. The data clearly demonstrated that the combined effects of infection and dietary deficiency resulted in a more severe reduction in plasma albumin values than either factor produced alone. The results are discussed with reference to the aetiology of hypoalbuminaemia and kwashiorkor in man.


2013 ◽  
Vol 38 (8) ◽  
pp. 844-853 ◽  
Author(s):  
Shari E. Smith ◽  
Rafaela Andrade Ramos ◽  
Roberto Refinetti ◽  
Jonathan P. Farthing ◽  
Phyllis G. Paterson

Protein-energy malnutrition (PEM), present in 12%–19% of stroke patients upon hospital admission, appears to be a detrimental comorbidity factor that impairs functional outcome, but the mechanisms are not fully elucidated. Because ischemic brain injury is highly temperature-sensitive, the objectives of this study were to investigate whether PEM causes sustained changes in temperature that are associated with an inflammatory response. Activity levels were recorded as a possible explanation for the immediate elevation in temperature upon introduction to a low protein diet. Male, Sprague-Dawley rats (7 weeks old) were fed a control diet (18% protein) or a low protein diet (PEM, 2% protein) for either 7 or 28 days. Continuous core temperature recordings from bioelectrical sensor transmitters demonstrated a rapid increase in temperature amplitude, sustained over 28 days, in response to a low protein diet. Daily mean temperature rose transiently by day 2 (p = 0.01), falling to normal by day 4 (p = 0.08), after which mean temperature continually declined as malnutrition progressed. There were no alterations in activity mean (p = 0.3) or amplitude (p = 0.2) that were associated with the early rise in mean temperature. Increased serum alpha-2-macroglobulin (p < 0.001) and decreased serum albumin (p ≤ 0.005) combined with a decrease in serum alpha-1-acid glycoprotein (p < 0.001) suggest an atypical acute-phase response. In contrast, a low protein diet had no effect on the signaling pathway of the pro-inflammatory transcription factor, NFκB, in the hippocampus. In conclusion, PEM induces an aberrant and sustained acute-phase response coupled with long-lasting effects on body temperature.


1979 ◽  
Vol 42 (1) ◽  
pp. 21-31 ◽  
Author(s):  
Marta Fiorotto ◽  
W. A. Coward

1. Rats were made oedematous by feeding them low-protein diets (protein: energy (P:E) 0.005) ad lib., and measurements were made of plasma and interstitial fluid colloid osmotic pressures (πp and πi respectively) and interstitial fluid hydrostatic pressure (Pi) before, and at the onset of, oedema formation. Taken together as (πp − πi + Pi) these forces oppose capillary pressure (Pc) and thus determine rates of transcapillary water filtration. Interstitial fluid was sampled, in non-oedematous and oedematous animals, from perforated capsules implanted subcutaneously for the measurement of Pi. Blood, plasma and interstitial fluid volumes were also determined.2. In Expt I comparisons were made between animals fed on a control diet (P:E 0.210) and the lowprotein diet. In normal animals the ratio πp:πi was approximately 2, but in protein deficiency it was increased since reductions in the absolute value of πi matched those in πp. These changes were observed 2 weeks after the start of the experiment and became more exaggerated when oedema appeared (weeks 18–22).3. Pi was normally negative with respect to atmospheric pressure but increased to values close to zero when oedema formation occurred.4. Despite the reductions in πp that were seen in the protein-deficient animals the sum of the forces opposing filtration (πp − πi + Pi) did not change significantly during the experiment.5. Plasma and interstitial fluid volumes expressed per kg body-weight (measured using 125I-albumin and 35SO42−) were unchanged as πp initially decreased in the protein-deficient animals but increased markedly with the onset of oedema.6. In Expt 2 comparisons were made between animals fed the low-protein diet ad lib. and others fed on the control diet in restricted amounts so that weight loss was the same in the two groups of animals.7. The wasting induced by restriction of the control diet did not produce reductions in πp or πi and values for Pi were normal. Changes in the animals fed on the low-protein diet were similar to those observed in Expt I. By using 51Cr-labelled erythrocytes it was shown that the expansion in plasma volume that occurred when oedema appeared in the protein-deficient animals was mainly due to a reduction in total erythrocyte volume. Blood volume did not increase significantly.8. It was concluded that in the hypoproteinaemia induced in the experimental animals reductions in the value of πp, which might otherwise result in an imbalance of forces that would produce excessive rates of transcapillary water filtration, were compensated for by reductions in πi. Increases in Pi also compensated but were quantitatively less important.9. The significance of the results is discussed in terms of the pathogenesis of oedema in kwashiorkor and the concept of an oncotic threshold for oedema formation in hypoproteinaemia.


1976 ◽  
Vol 36 (2) ◽  
pp. 219-230
Author(s):  
P. G. Lunn ◽  
R. G. Whitehead ◽  
B. A. Baker

1. Free amino acid concentrations in the plasma have been compared with those in liver and quadriceps muscle, in rats fed on diets containing 209 (control) and 31 (low-protein) g protein/kg. The effects of the low-protein diet on diurnal variations in these values were also measured.2. In the plasma, the total amino acid concentration was significantly lower in animals given the low-protein diet, at all times of day except 12.00 hours. In the liver, and to a lesser extent the muscle, total amino acid concentration was maintained.3. In the control animals, diurnal variation in the concentrations of both essential and non-essential amino acids was very similar in plasma, liver and muscle. In animals given the low-protein diet, although the same diurnal pattern was maintained for non-essential amino acids, that occurring among the essential amino acids had virtually disappeared.4. In plasma, the mean 24 h concentration of essential amino acids decreased from 24· mmol/l in control animals to only 1·29 mmol/l in the low-protein-fed animals. Concentrations in muscle and liver were reduced by a similar proportion (from 8·6 to 5·56 μmol/g and from 8·67 to 5·05 μmol/g respectively). Conversely the concentrations of non-essential amino acids in animals given the low-protein diet were increased in plasma (from 1·53 to 2·00 mmol/l), muscle (from 12·5 to 14·3 μmol/g), and liver (from 16·8 to 20·5 μmol/g), muscle showing the lowest increase.5. With the exceptions of lysine, threonine, cystine and tyrosine, the concentrations of all other essential amino acids were reduced more in liver than in muscle. The relationship between this and the failure to maintain plasma albumin concentrations is discussed.


2019 ◽  
Vol 109 (3) ◽  
pp. 517-525 ◽  
Author(s):  
Casey M Rebholz ◽  
Zihe Zheng ◽  
Morgan E Grams ◽  
Lawrence J Appel ◽  
Mark J Sarnak ◽  
...  

ABSTRACT Background Accurate assessment of dietary intake is essential, but self-report of dietary intake is prone to measurement error and bias. Discovering metabolic consequences of diets with lower compared with higher protein intake could elucidate new, objective biomarkers of protein intake. Objectives The goal of this study was to identify serum metabolites associated with dietary protein intake. Methods Metabolites were measured with the use of untargeted, reverse-phase ultra-performance liquid chromatography–tandem mass spectrometry quantification in serum specimens collected at the 12-mo follow-up visit in the Modification of Diet in Renal Disease (MDRD) Study from 482 participants in study A (glomerular filtration rate: 25–55 mL · min−1 · 1.73 m−2) and 192 participants in study B (glomerular filtration rate: 13–24 mL · min−1 · 1.73 m−2). We used multivariable linear regression to test for differences in log-transformed metabolites (outcome) according to randomly assigned dietary protein intervention groups (exposure). Statistical significance was assessed at the Bonferroni-corrected threshold: 0.05/1193 = 4.2 × 10−5. Results In study A, 130 metabolites (83 known from 28 distinct pathways, including 7 amino acid pathways; 47 unknown) were significantly different between participants randomly assigned to the low-protein diet compared with the moderate-protein diet. In study B, 32 metabolites (22 known from 8 distinct pathways, including 4 amino acid pathways; 10 unknown) were significantly different between participants randomly assigned to the very-low-protein diet compared with the low-protein diet. A total of 11 known metabolites were significantly associated with protein intake in the same direction in both studies A and B: 3-methylhistidine, N-acetyl-3-methylhistidine, xanthurenate, isovalerylcarnitine, creatine, kynurenate, 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE (P-16:0/20:4), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4), 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4), sulfate, and γ-glutamylalanine. Conclusions Among patients with chronic kidney disease, an untargeted serum metabolomics platform identified multiple pathways and metabolites associated with dietary protein intake. Further research is necessary to characterize unknown compounds and to examine these metabolites in association with dietary protein intake among individuals without kidney disease. This trial was registered at clinicaltrials.gov as NCT03202914.


1973 ◽  
Vol 103 (5) ◽  
pp. 720-729 ◽  
Author(s):  
Vernon R. Young ◽  
Gaston Vilaire ◽  
Paul M. Newberne ◽  
Robert B. Wilson

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