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Factors affecting the total protein, albumin & globulin levels in humans

Hundreds of proteins are found dissolved within the plasma of the blood
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Jerry Kaneko, 1997)
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Total serum protein is the quantitative measurement of the concentrations of all proteins present
within the serum, excluding clotting factors
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The normal serum protein level is 6-8 g/dl
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5-5 g/dl & globulin levels
making up the total at 2-2
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Plasma proteins such as albumin & globulin account for the majority
of proteins located within the plasma & serve an innumerable variety
of essential functions within the body
...
As all plasma proteins,
albumin in synthesized by the liver & catabolised by all metabolically
active tissues, it is the most osmotically active plasma protein due to
its abundance & small size & accounts for 75% of osmotic activity of
plasma (J
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As well as regulating blood volume
through maintaining the colloid osmotic pressure, albumin also serves
as a general binding & transport protein, primary responsible for the
transport of non-esterified fatty acids, hormones, haeme & lipophilic
xenobiotics through the bloodstream (Lexa KW, 2014)
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Structure of Human Albumin with binding sites
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Sites I & II are shown in a purple colour & the haeme
binding sites are shown in blue
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Compromised of hundreds of serum proteins including carrier proteins, complement &
immunoglobulins (Walker HK, 1990) globulins generally serve as antibodies involved in defence
mechanisms of the body & transport of substances in the blood & are comprised of four major
groups: α1, α2, β, & γ (M
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Majority of these globulins are synthesized by
the liver, however immunoglobulins are synthesized by plasma B cells
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Lee Lerner,
2003)
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Lee Lerner, 2003)
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Immunoglobulins come in a variety of known
isotopes, with there being five known isotopes recognised in placental
mammals: IgG, IgA, IgM, IgE, & IgD (James D
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The
quantities of each of these globulins in the blood can be diagnostic of
specific diseases or malfunctions in the body
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Diagram showing the structure of an
immunoglobulin molecule
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(George L
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These chains are held together by a combination of
covalent interchain disulphide bonds & non-covalent interactions, forming a bilateral symmetric
structure (D
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Each heavy & light chain possesses a variable & constant region,
however the light chains constant & variable regions & are either kappa (κ) or lambda (λ) type
(Walker HK, 1990)
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Elevations of serum
albumin concentration occur infrequently & is primarily due to severe dehydration, this being the
only clinical cause of elevation (Walker HK, 1990)
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The most common causes of hypoalbuminemia are related to acute & chronic inflammatory
disorders, with there being four probable causative factors, including heamodilution, increased
consumption by cells locally, loss of extravascular space & decreased synthesis (Judy Hankins, 2006)
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Also loss of albumin can occur through a kidney disorder known as nephrotic
syndrome, proliferation permeability of the capillary walls of the glomerulus leads to high presence
of protein passing from the blood serum into the urine
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Consequences of
hypoalbuminemia can lead to a shift of fluid from the intravascular to the interstitial space, thus
resulting in intravascular volume depletion & formation of edema (Walker HK, 1990)
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Alpha 1&2 globulins
are simply endogenously synthesised either due to acute & chronic inflammatory responses to
disease also because alpha-1 antitrypsin is an acute phase reactant (Walker HK, 1990) whilst betaglobulins are elevated on account of hyperlipidaemia; a disorder in which the body possesses
complications in the breakdown of fats & is one of the most striking features of nephrotic syndrome
(J
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Beaumont, 1974)
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Although synthesis of gamma-globulins appears to be largely dependent on antigenic experience
through exposure to foreign antigenic substances e
...
bacterial & viral infections, gamma-globulin
catabolism is generally accelerated due to chronic inflammatory disease such as plasma cell
malignancies e
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multiple myelomas (John L
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However multiple myeloma is more predominant; a neo plastic plasma cell disorder that is
categorised by clonal proliferation of malignant plasma cells within the bone marrow including
overproduction of monoclonal immunoglobulins, presence of monoclonal proteins within the blood/
urine & related organ dysfunction (Antonio Palumbo, 2011)
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Abnormal elevations in gamma-globulins are seen in both acute & chronic liver disease, acute liver
disease such as hepatitis leads to a moderate increase in gamma-globulins, though levels return to
normal state once the hepatitis subdues
...
B
...

Depletion of alpha-1 globulin concentration simply occurs due to congenital alpha 1 antitrypsin
deficiency & decreased production of the globulin as result of liver disease (Theodore X
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Alpha-2 globulin depletion is affected by acute haemolytic anaemia & haemolysis of the red
blood cells, haptoglobin (α2) decreases after haemolytic reaction because the haptoglobin
complexes with free haemoglobin & is cleared from circulation (Walker HK, 1990) whereas Betaglobulin reduction is attributed to abnormally low levels of LDL & malnutrition, the body not
absorbing enough protein efficiently
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The serum
concentration of gamma-globulins is decreased & fractional rate of catabolism increased, implying
that kidney contributes to presence of proteinuria (Kaysen GA, 1990)
...

Primary form hypogammaglobulinemia implies a merely reduced rate of synthesis of gammaglobulins, whereas the secondary from results in increased rate of breakdown (Shardah Agarwal,
2007)
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The most widely used method of measuring serum protein is with biuret reaction due to its
simplicity, rapidity & reliability
...
The intensity of the violet colour is directly proportional to concentration of
protein (Walker HK, 1990)
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Sensitivity of the reaction can be increased by addition of Folin-Ciocalteu reagent; Cu2+ is used
as in the Biuret assay; phosphomolybdate is reduced by tyrosine & tryptophan residues which
generates an intense blue colour measured at 750nm (Rea, 2015)
...

Electrophoresis is another common, easy & inexpensive means of fractionating serum proteins;
exposed to an electrical current the differences in the proteins electrical charge will cause them to
migrate at different rates towards the anode or cathode, separating them into discrete bands
(Theodore X
...
Characteristic but non-specific patters are associated with various
conditions however the only diagnostic use of this technique is to detect monoclonalimmunoglobulins, of which are found in patients with myelomas and other malignancies of B-cells
(Theodore X
...
Immunoelectrophoresis is used to evaluate an increase in the
gamma-globulin fraction, specific to each antisera to each immunoglobulin type are used to
determine whether the increase is monoclonal or polyclonal (Walker HK, 1990)
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Diagram displaying the typical normal pattern for serum
protein electrophoresis
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(Theodore X
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Figure 4
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O’Connell, 2005)
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O
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Virtually all proteins exhibit a strong UV absorbance at 210nm, displaying the sensitivity of
the test & are generally proportional to the size of the protein (Rea, 2015)
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Words:
1557/1650

References
 Walker HK, Hall WD, & Hurst JW
...
Clinical Methods: The
history, physical, & laboratory examination, 3rd edition
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Jerry Kaneko, John W
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Bruss (1997) Clinical Biochemistry of Domestic Animals
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USA
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 Lexa KW, Dolghih E, Jacobson MP (2014) A Structure-Based Model for Predicting Serum Albumin Binding
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doi:10
...
pone
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Ahmadi-hamedani, K
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Kokhaei, M
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Mahdavi (2014) Comparison of effects of
age & sex on serum protein electrophoretic patters in one-humped camels (camelus dromedarius) in
Semnan, Iran
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4(1): 4-8
 K
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Detroit
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 D
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(2015) Antibody structure & classes of immunoglobulins
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Thermo Scientific
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piercenet
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Plasma & blood proteins
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 James D
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O’Connor (2010) The immune system of Ruminants
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Advancing Nutrition for Healthy Animals
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theomnigendifference
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pdf
[Assessed: 28/02/2015]
 George L
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(2009) Immunochemical Staining Methods
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Dako North
America, Carpinteria, California
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(2006) The role of albumin in fluid & electrolyte balance
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Volume
29(5) p 260-265
 John L
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Robinson
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Metabolism
service, National cancer institute, National industries of health, Bethesda
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L
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Guedon & R
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(1974) Nephrotic syndrome, monoclonal
gammopathy & auto-immune hiperlipidemia
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M
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Foch et Institute National de la Sante et de la Recherche Midicale, France
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Harris & William E
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(2012) Multiple Myeloma & related serum protein disorders
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1st edition
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(2011) Multiple Myeloma
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Giovanni Battista, Turin,
Italy (A
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); & the Department of Medicine, Harvard Medical School, Division of Hematolgic Neoplasia,
Dana–Farber Cancer Institute, Boston (K
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 T
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Tomasi Jun & William A
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(1964) Serum gamma-globulins in acute & chronic liver diseases
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University of Vermont College of Medicine, Burlington, Vermont, &
Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire
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O’Connell, Timothy J
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(2005) Understanding & interpreting serum
protein electrophoresis
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Kaiser Permanente Woodland Hills Family Medicine Residency
Program
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1;71(1):105-112
 Kaysen GA & Al Bander H
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PubMed
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 Shardah Agarwal & Charlotte Cunningham-Rundles
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NCIB
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99(3): 281–283
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(2015) Protein assays: Determining protein concentration
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 C
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B Okoye, A
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Chukwuneke, N
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Ekere and J
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Ihedioha (2013) Simultaneous ultraviolet-visible (UVVIS) spectrophotometric quantitative determination of PH, Hg, Cd, As and Ni ions in aqueous solution using
cyaniding as a chromogenic reagent
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8(3), pp
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 William Marshall
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(find full reference)



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