{"id":822,"date":"2015-02-16T08:40:42","date_gmt":"2015-02-16T08:40:42","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=822"},"modified":"2017-01-05T05:59:34","modified_gmt":"2017-01-05T05:59:34","slug":"serum-protein-albumin-globulin-levels-and-ag-ratio-in-hiv-positive-patients","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol2no2\/serum-protein-albumin-globulin-levels-and-ag-ratio-in-hiv-positive-patients\/","title":{"rendered":"Serum Protein, Albumin, Globulin Levels, and A\/G Ratio in HIV Positive Patients"},"content":{"rendered":"

Introduction<\/strong><\/p>\n

AIDS is a devastating disease caused by HIV, that render the host profoundly immunoincompetent. Diarrhoea is a common presenting feature of AIDS.\u00a0 Many patients with AIDS who develop diarrhea have some degree of jejunal villous atrophy and over 70% have some evidence of malabsorption.\u00a0 In AIDS diarrhea is often associated with reduced serum albumin (< 10 gm\/lt), probably due to hypercatabolism, though other factors may contribute, including malabsorption and a protein losing enteropathy as indicated by an increase in faecal alpha-1-antitrypsin.<\/p>\n

Severe weight loss is common among AIDS patients. HIV wasting syndrome is defined as weight loss of over 10 % of baseline with no other cause over 30 days or more either diarrhea or weakness with fever. In weight loss of malnutrition the fat tissue is preferentially depleted and muscle protein is preserved. In contrast acute infection, trauma, burns tend to be accompanied by protein catabolism and a negative nitrogen balance.\u00a0 Although serum total protein estimation has limited diagnostic importance when compared to albumin because of the compensatory increases in other serum proteins (the globulins) during infections, its relevance in the evaluation of patients with some clinical conditions such as malnutrition, malignancy, renal and liver diseases & immune disorders cannot be ignored [Gray CH, etal (1985)].<\/p>\n

Material and Methods<\/strong><\/p>\n

Clinical Material \u2013 The present work, on \u201cthe study of serum protein, albumin, globulin and A:G ratio in HIV positive patients\u201d, was carried out on 40 HIV positive patients admitted in Medicine wards in Government Medical College, Aurangabad, Maharashtra. Forty healthy & jHIV negative control cases were included in the study.\u00a0 Mean age of morbid (27 males & 13 females) & control cases (28 males and 12 females) was approximately 35 years.<\/p>\n

Inclusion criteria \u2013 HIV positive patients were included.<\/p>\n

Exclusion criteria \u2013 Patients suffering from diabetes, renal disorders, and cases with fever & vomiting were excluded.<\/p>\n

Methods<\/strong><\/p>\n

The serum samples were collected from the Department of Microbiology after they were confirmed to be HIV positive by the ELISA Recombigen Test and Rapid Capillus Latex Agglutination Test. Blood samples from healthy individuals were collected in the OPD, processed for HIV testing in the Department of Microbiology and after confirming HIV negativity the samples were analyzed biochemically. All blood samples were collected in plain bulbs. The biochemical investigations were performed on the fully automated analyzer \u2013 Erba Superstat 919, except serum globulin and A: G ratio, which was calculated mathematically. All the values were calculated in gram%.\u00a0 The data were statistically analyzed using \u2018t-test\u2019.\u00a0 Following table shows the method employed with normal values of all biochemical parameters tested.<\/p>\n\n\n\n\n\n\n\n
S.No:<\/strong><\/td>\nBiochemical Parameter<\/strong><\/td>\nMethod<\/strong><\/td>\nWavelength<\/strong><\/p>\n

(nms)<\/strong><\/td>\n

Formula<\/strong><\/td>\nNormal Value (gm%)<\/strong><\/td>\n<\/tr>\n
1.<\/td>\nTotal Protein<\/td>\nBiuret Method<\/td>\n546<\/td>\nA (T)<\/u> * Conc of S (6 gm%)<\/sub><\/p>\n

A (S)<\/p>\n

 <\/td>\n

6 \u2013 8.3<\/td>\n<\/tr>\n
2.<\/td>\nSerum Albumin<\/td>\nBCG (Bromo Cresol Green) Enzymatic method (Doumas et al)<\/td>\n659<\/td>\nA (T)<\/u> * Conc of S (6 gm%)<\/sub><\/p>\n

A (S)<\/p>\n

 <\/td>\n

3.2 \u2013 5.3<\/td>\n<\/tr>\n
3.<\/td>\nSerum Globulin<\/td>\n<\/td>\n<\/td>\n(serum total protein) \u2013 (serum albumin)<\/td>\n1.8 \u2013 3.6<\/td>\n<\/tr>\n
4.<\/td>\nA: G<\/td>\n<\/td>\n<\/td>\nserum albumin\/serum globulin<\/td>\n1.5:1 \u2013 2:1<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Results and Discussion<\/strong><\/p>\n

\u00a0Table 1:\u00a0 Mean Age in Control and Morbid Group \u2013<\/strong><\/p>\n\n\n\n\n\n
S.No:<\/td>\nGroup<\/td>\nMean Age (Years)<\/td>\n<\/tr>\n
1.<\/td>\nControl<\/td>\n35.17<\/td>\n<\/tr>\n
2.<\/td>\nHIV Positive Cases<\/td>\n34.65<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

The mean age of the control group including morbid group was calculated to be 35.17 years (22 to 53 years) & 34.65 years (22 to 55 years).<\/p>\n

Table 2:\u00a0 Sex Differentiation in Morbid and Control Group \u2013<\/strong><\/p>\n\n\n\n\n\n
S.No:<\/td>\nGroup<\/td>\nNo: of Males<\/td>\nNo: of Females<\/td>\n<\/tr>\n
1.<\/td>\nControl<\/td>\n28<\/td>\n12<\/td>\n<\/tr>\n
2.<\/td>\nHIV Positive<\/td>\n27<\/td>\n13<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

The above table shows the sex differentiation in morbid test and control groups<\/p>\n

Table 3:\u00a0 Mean \u00b1 SD in Control & Morbid Groups \u2013<\/strong><\/p>\n\n\n\n\n\n\n\n\n
S. No:<\/strong><\/td>\nBiochemical<\/strong><\/p>\n

Parameter<\/strong><\/td>\n

Max-Min Range [Control]<\/strong><\/td>\nMax-Min Range [Morbid]<\/strong><\/td>\nMean \u00b1 SD (gram %)<\/strong><\/td>\n<\/tr>\n
Control Group<\/strong><\/td>\nMorbid Group<\/strong><\/td>\n<\/tr>\n
1.<\/td>\nTotal Protein<\/td>\n7.5-6.7<\/td>\n8.3-6.9<\/td>\n7.07 \u00b1 0.22<\/td>\n7.43 \u00b1 0.43<\/td>\n<\/tr>\n
2.<\/td>\nAlbumin<\/td>\n5.0-4.0<\/td>\n3.2-2.4<\/td>\n4.45 \u00b1 0.26<\/td>\n2.67 \u00b1 0.34<\/td>\n<\/tr>\n
3.<\/td>\nGlobulin<\/td>\n3.3-2.1<\/td>\n5.6-3.9<\/td>\n2.6 \u00b1 0.29<\/td>\n4.76 \u00b1 0.41<\/td>\n<\/tr>\n
4.<\/td>\nA:G Ratio<\/td>\n2.3-1.2<\/td>\n0.7-0.3<\/td>\n1.7 \u00b1 0.26<\/td>\n0.56 \u00b1 0.1<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Thus following is evident from the above table \u2013<\/p>\n

The mean serum total protein level in control group was 7.07 \u00b1 0.22 gm% which was increased to 7.43 \u00b1 0.43 gm % in HIV positive patients; statistical analysis showed significant (p<0.01) relationship between control & morbid groups.<\/p>\n

The mean serum albumin level in the control group was 4.45 \u00b1 0.26 gm % which was found to be decreased upto 2.67 \u00b1 0.34gm % in HIV positive patients and the decrease was statistically highly significant (p<0.001).<\/p>\n

The mean serum globulin level in the control group was 2.6 \u00b1 0.29 gm % which was increased to 4.76 \u00b1 0.42 in HIV positive patients.\u00a0 It was found to be statistically highly significant (p<0.001).<\/p>\n

The mean serum A: G ratio in the control group was 1.7 \u00b1 0.26 whereas in HIV positive patients it was found to be reversed; values being 0.56 \u00b1 0.1 (p < 0.001).<\/p>\n

The above data on statistical analysis showed following p values \u2013<\/p>\n

Table 4:\u00a0 Statistical Analysis between Control Group Vs Morbid Group \u2013<\/p>\n\n\n\n\n\n\n\n
S.No:<\/strong><\/td>\nBiochemical<\/strong><\/p>\n

Parameter<\/strong><\/td>\n

p-value<\/strong><\/td>\nTest of Significance<\/strong><\/p>\n

[t-test]<\/strong><\/td>\n<\/tr>\n

1.<\/td>\nTotal Protein<\/td>\np < 0.01<\/td>\nSignificant<\/td>\n<\/tr>\n
2.<\/td>\nAlbumin<\/td>\np < 0.001<\/td>\nHighly Significant<\/td>\n<\/tr>\n
3.<\/td>\nGlobulin<\/td>\np < 0.001<\/td>\nHighly Significant<\/td>\n<\/tr>\n
4.<\/td>\nA:G Ratio<\/td>\np < 0.001<\/td>\nHighly Significant<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

According to the present study mean serum total protein level in control group was 7.07 \u00b1 0.22 gm% which was increased to 7.43 \u00b1 0.43 gm % in HIV positive patients (p<0.01).\u00a0 Ulrich R. etal (1989) demonstrated the average value of total serum protein for HIV positive patients was 73 gm\/lt whereas for serum albumin it was 38 gm\/lt.(19)<\/sup><\/p>\n

The mean serum albumin level in the control group in the present study was 4.45 \u00b1 0.26 gm % which was found to be decreased upto 2.67 \u00b1 0.34gm % in HIV positive patients and the decrease was statistically highly significant (p<0.001).\u00a0 Hypoalbuminemia and was reported by Schniedermann D etal (1987) (3.2 gm %), Dworkin B., etal (1987) (3.0 gm%), Dworkin B, etal (1985) (mean = 3.3 gm\/dl), & Keithley J.K. etal (1989).(16, 5, 4, 11)<\/sup>\u00a0 Guenter P. et al (1993) observed that the serum albumin levels and weight loss were related to CD 4 counts. They stated hat the relative risk for subjects with low serum albumin levels (<3.5 gm\/dl) was 3.6 times greater (p<0.021) than that for subjects with normal serum albumin levels (>3.5 gm\/dl) and CD 4 counts.(10)<\/sup> Fernandez p etal (1995) evaluated the serum albumin levels < 30 gm\/lt were related with a poor prognosis.(7)<\/sup>\u00a0 Scuttman U et al (1995) observed decreased serum albumin levels were observed in 14 % predominantly in more advanced stage of the disease. They stated that 14 of the 32 patients died and the survivors shoed significantly larger initial serum albumin levels compared with non survivors.(17)<\/sup>\u00a0 Gerard L. et al (1996) concluded that factors contributing to a higher mortality included type of opportunistic infection, weight, CD 4 cell count, and serum albumin level.(8)<\/sup> Wilcox C. M. et al (1996) stated, that in a study of 71 HIV positive patients, death was strongly associated with reduced serum albumin concentration.(20)<\/sup> Colin J. F. etal (1999) stated that HIV positive patients had lower serum albumin levels (p = 0.0009).(3)<\/sup>\u00a0 Joel E. Gallant (2004) explained that<\/em> a low albumin typically occurs at advanced stages of HIV disease and reflects poor nutritional status. However, the elevated total protein and globulin fraction can occur in otherwise healthy HIV-positive individuals.\u00a0 It probably reflects a generalized, polyclonal gammopathy, with increased antibody production, which is an attempt on the part of the immune system to compensate for cellular immunodeficiency.<\/p>\n

The mean serum globulin level in the control group was 2.6 \u00b1 0.29 gm % which was increased to 4.76 \u00b1 0.42 in HIV positive patients (p<0.001).\u00a0 The increase in the anion gap may be associated with increased level of IgG (hyperglobulinemia).<\/p>\n

Hyperglobulinemia in HIV patients was demonstrated by studies by Slucher B. etal (1993), Quensel A et al (1994), Miguez \u2013 Burban M.J. et al (1995) ( p = 0.003), & Moja P etal (1997).(18, 15, 13, 14) <\/sup>\u00a0Hyperglobulinemia seen in HIV positive patients may be due to increased levels of IgA and IgG in this disease.<\/p>\n

Ball S.G. (1994) stated that AIDS diarrhea is often associated with reduced serum albumin, as low as 10 gm\/lt in severe cases, probably due to hypercatabolism, though other factors may contribute including malabsorption and protein losing enteropathy. He also states that polyclonal hyperglobulinemia may be sufficient to raise the total protein typically by some 10 to 15 gm\/lt.(1)<\/sup><\/p>\n

Khot V.V. (1999) concluded that the total serum protein levels and serum globulin levels in HIV positive alcoholics and HIV positive non alcoholics were increased; serum albumin levels & A: G ratio were reduced in the above groups, but the differences were not statistically significant (p <0.05).\u00a0 She stated that the total serum proteins levels (p < 0.001) & serum globulin levels (p<0.001) in HIV positive non alcoholics were higher than HIV negative non alcoholics.\u00a0 Serum albumin levels were significantly decreased in HIV positive non alcoholics compared to HIV negative non alcoholics (p < 0.001). When HIV positive alcoholics were compared with HIV negative non alcoholics the total protein levels in HIV positive alcoholics was increased (p<0.001) whereas serum albumin levels were decreased in HIV positive alcoholics (p< 0.05). Serum globulin levels were increased in HIV positive alcoholics (p<0.001). (12)<\/sup>\u00a0 The present study demonstrates mean serum A:G ratio to be 1.7 \u00b1 0.26 (controls) whereas in morbid group it was found to be reversed; values being 0.56 \u00b1 0.1 (p < 0.001).\u00a0 Although serum total protein estimation has limited diagnostic importance when compared to albumin because of the compensatory increases in other serum proteins (the globulins) during infections, its relevance in the evaluation of patients with some clinical conditions such as malnutrition, malignancy, renal and liver diseases and immune disorders cannot be ignored [Gray CH, etal (1985)].\u00a0 Decrease in serum total protein in HIV infection has been associated with either increased losses &\/or catabolism or as a result of reduction in intake &\/or absorption due to sores in the mouth, pharynx &\/or oesophagus, fatigue, depression and side effects of medications (Macallan DC) (1999).(6)<\/sup><\/p>\n

Guardia J. A. et al (1997) concluded that in HIV positive patients the serum albumin level was on an average 2.3 gm %. The mean value of serum globulin in HIV positive patients was 3.1 gm %. They concluded that globulins play an important role in maintaining oncotic pressure in low albumin states.(9)<\/sup>\u00a0 Cirasino L. et al(1996) demonstrated in patients wherein the survival was significantly reduced for those groups which at the beginning of the followup showed CD 4 lymphocyte count < 240\/cubic mm, serum albumin < 4.13 gm\/dl (p = 0.04) and serum IgA > 2.5 gm\/dl (p = 0.043).(2)<\/sup><\/p>\n

Summary and Conclusions<\/strong><\/p>\n

Though the serum albumin levels were decreased in HIV positive patients, the serum globulin levels were increased, which resulted in the total serum protein levels remaining apparently in normal range.\u00a0 The serum globulin was increased above the upper limit of normal in all HIV positive patients.\u00a0 The A: G ratio was found to be reversed in HIV positive patients. Globulins play an important role in maintaining the oncotic pressure in low albumin states in these patients.\u00a0 HIV positive patients with serum albumin lower than 3 gm % generally have a poor prognosis; hence the serum albumin level can be used as a prognostic indicator.\u00a0 These depressed albumin levels could reflect the poor nutritional status, catabolic state of chronic disease evidenced by significant weight loss.<\/p>\n

References\u00a0<\/strong><\/p>\n

    \n
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  16. Schneiderman JD, Areneson DM , Cello JP et al. Hepatic disease in patients with AIDS. Hepatology 1987.\u00a0 7(5): 925-30.<\/li>\n
  17. Scuttman U, Ockenga J, Selberg O et al. Incidence and prognostic value of malnutrition and wasting in HIV infected outpatients. J AIDS and Human Retrovirol 1995.\u00a0 8(3): 239-246.<\/li>\n
  18. Slucher B, LevinsonSS et al.\u00a0 HIV and anion gap. Ann Clin Lab Science 1993.\u00a0 23(4): 249-55.<\/li>\n
  19. Ulrich R, Zeitz M, Heise W et al. Small intestinal structure and function in patients infected with HIV \u2013Evidence for HIV induced enteropathy. Ann Int Med 1989.\u00a0 111: 15-21.<\/li>\n
  20. Wilcox CM, Rabeneck L, Friedman S. AGA Technical Review. Malnutrition and cachexia, chronic diarrhea and hepatobiliary disease in patients with HIV. Gastroenterol 1996.\u00a0 111: 172-75.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Introduction AIDS is a devastating disease caused by HIV, that […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[],"class_list":["post-822","post","type-post","status-publish","format-standard","hentry","category-vol2no2"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/822","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=822"}],"version-history":[{"count":4,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/822\/revisions"}],"predecessor-version":[{"id":13152,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/822\/revisions\/13152"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=822"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=822"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=822"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}