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Hyperproteinaemia in Cats and Dogs: an Approach to Diagnostic Investigation

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Hyperproteinaemia in Cats and Dogs: an Approach to Diagnostic Investigation Peer Reviewed VETcpd - Internal Medicine Hyperproteinaemia in cats and dogs: An approach to diagnostic investigation Increased serum protein concentrations can be associated with infl ammatory, infectious and neoplastic conditions. Hyperproteinaemia is a signifi cant biochemical fi nding in both dogs and cats that warrants further investigation. Due to the wide range of differential diagnoses it is essential that a systematic approach to the investigation of hyperproteinaemia is implemented in order to identify the underlying aetiology. This article will discuss the diagnostic approach to hyperproteinaemia and the potential differential diagnoses. Cecilia Stilwell BVMS MRCVS Cecilia Stilwell graduated from the Key words: Hyperproteinaemia, monoclonal gammopathy, polyclonal University of Glasgow in July 2014. gammopathy, serum protein electrophoresis She started her career in a busy fi rst opinion small animal practice near (monoclonal gammopathy) from Reading. Here she developed a keen Introduction proliferation of multiple plasma cell interest in internal medicine. Albumin and globulins account for the majority of the plasma proteins. lineages (polyclonal gammopathy). This Cecilia has completed a rotating Albumin is a large osmotically active distinction can allow the clinician to internship at Dick White Referrals, protein which accounts for approximately prioritise their list of diff erential diagnoses Cambridgeshire. During this time she 75% of colloid oncotic pressure (COP) accordingly. obtained a Post Graduate Certifi cate (McGrotty et al. 2016). Globulins in Veterinary Medicine and Surgery This article will discuss the diff erential from the University of Nottingham. comprise of a heterogeneous group of diagnoses for hyperproteinaemia and how Throughout her career she has treated proteins that include immunoglobulins to conduct a methodical investigation to patients with a variety of haematological (a.k.a. antibodies), acute phase proteins characterise the underlying aetiology. conditions. This has subsequently (APPs) and enzymes. Immunoglobulins become one of her primary interests (IgG, IgM, IgA and IgE) account for Characterising the within internal medicine. the largest component of globulins. They are synthesised by cells of B-lymphocyte hyperproteinaemia Email: [email protected] lineage, mostly diff erentiated B cells Artefact vs. true known as plasma cells, in response to Following the detection of hyperprotein- antigenic stimulation. Globulins are also aemia it is important to consider whether involved in drug transport and contribute the result could be attributed to laboratory to COP. Fibrinogen and clotting factors artefact. Measurement techniques based on are also present within plasma, but are refractometry or wet chemistry are both removed during the clotting process that subject to error. A lipaemic or, to a lesser forms serum. extent, a haemolysed sample can cause an If identifi ed during the investigation of artefactual increase in the measured serum clinical disease in cats and dogs, increased protein concentration. In addition, with serum or plasma protein concentrations some analysers, the presence of hyperbili- (hyperproteinaemia) is a useful and rubinaemia may result in an artefactual signifi cant fi nding that warrants further increase in the measured serum protein investigation. Hyperproteinaemia can concentration. be associated with either reduced whole body water levels (i.e. volume contractions Relative vs. absolute due to dehydration) or increased serum Once true hyperproteinaemia has been protein production due to a variety of established the investigation can proceed to For Internal Medicine referrals in infl ammatory, infectious and/or neoplastic diff erentiate between a relative or absolute your area: vetindex.co.uk/medicine conditions. hyperproteinaemia (Figure 1). For Lab Tests and Equipment: vetindex.co.uk/Lab Serum protein electrophoresis (SPE) is a In relative hyperproteinaemia there is a laboratory technique used to separate the proportional increase in all protein fractions Market your referrals in VetIndex! serum protein into measurable fractions. such that the albumin and globulin ratio is For further information call us on SPE can diff erentiate proliferation of normal. Typically, albumin concentration 01225 445561 or email: [email protected] a single plasma cell or B-lymphocyte is increased above the reference interval, VETcpd - Vol 4 - Issue 4 - Page 23 VETcpd - Internal Medicine with or without elevations in globulins. This form of hyperproteinaemia is often accompanied by erythrocytosis and Hyperproteinaemia possibly pre-renal azotaemia. It occurs as a result of haemoconcentration (i.e. dehydration leading to reduced whole Confirmed result Laboratory artefact e.g. lipaemia, haemolysis, body water levels) and will resolve hyperbilirubinaemia following correction of uid de cits. In the clinical setting there may be a history of increased uid losses (e.g. Repeat analysis on new vomiting; diarrhoea; polyuria) or reduced sample water intake (e.g. water deprivation). Physical examination ndings may reveal evidence of dehydration (e.g. dry mucus Relative hyperproteinaemia Absolute hyperproteinaemia membranes; skin tent). In absolute hyperproteinaemia there is increased production of either Haemoconcentration / Hyperalbuminaemia Hyperglobulinaemia dehydration globulin or (rarely) albumin, resulting in an abnormal albumin to globulin ratio. Confirm with serum Monitor. Absolute hyperproteinaemia secondary protein electrophoresis Recheck once rehydrated Assess for underlying Evaluate the liver to hyperglobulinaemia occurs as a result inflammatory / infectious of increased globulin production due to aetiology in ammation, infection or neoplasia. In many cases there is also a ‘compensatory’ Serum protein hypoalbuminaemia. A single case report electrophoresis describes absolute hyperproteinaemia secondary to hyperalbuminaemia in a dog Monoclonal / biclonal with a massive hepatocellular carcinoma Polyclonal gammopathy Oligoclonal gammopathy gammopathy (Cooper et al. 2009). In this case there were no clinical or clinicopathological ndings consistent with dehydration or Infection / inflammation Neoplasia >> Infection / haemoconcentration, and the hyperal- > neoplasia inflammation buminemia resolved following surgical removal of the neoplasia. Physical exami- nation ndings relating to increased blood Figure 1: Initial approach to hyperproteinaemia. viscosity (i.e. hyperviscosity syndrome) may been seen in dogs and cats with and electrical charge) by application Alpha-globulin fraction hyperproteinaemia. These include bleeding of an electrical charge across a strip of The α1-globulin fraction includes: diathesis, hypertension, retinopathy and agarose gel or cellulose acetate. Separated protease inhibitor α1-antitrypsin; APP neurological abnormalities. proteins are stained and their density α1-acid glycoprotein; and lipid transport The greater the degree of hyperprotein- measured, resulting in a graphical trace protein α1-lipoprotein. This fraction can aemia the more signi cant the nding (a.k.a. electrophoretogram; Figures 2 be increased with pregnancy, neoplasia and and the greater the need for further and 3A-D). Capillary gel electrophoresis acute in ammation. has more recently been described as an investigation. Mild hyperglobulinaemia is The α2-globulin fraction includes: frequently encountered with many chronic alternative method. The shape of the APPs ceruloplasmin, haptoglobin and electrophoretogram can be evaluated and infectious and in ammatory diseases. α2-macroglobulin; hormone transport Moderate to severe hyperglobulinaemia is the approximate protein concentrations protein thyroxine-binding globulin; and more frequently associated with chronic for each fraction calculated from the renin substrate angiotensinogen. This systemic infection or lymphoproliferative percentage density and total protein fraction can be increased in the presence of disorders. The history, physical examination concentration. acute in ammation, nephrotic syndrome, and clinicopathological ndings, including and advanced diabetes mellitus. serum protein electrophoresis, should be Serum Protein Fractions considered together to allow prioritisation Serum proteins are separated into six Beta-globulin fraction of the list of di erential diagnoses (Table 1). fractions: albumin and alpha-1 (α1), alpha-2 The β1-globulin fraction is primarily (α2), beta-1 (β1), beta-2 (β2), and gamma (γ) composed of transferrin, a negative APP. globulins (Figure 2). Electrophoresis The β2-globulin fraction includes: Electrophoresis is a relatively inexpensive, Albumin fraction β-lipoproteins; complement; C-reactive specialist laboratory technique that can In the healthy cat or dog, albumin is the protein (CRP); and some immunoglobu- be applied to both serum and urine largest protein fraction of serum, it is lins (primarily IgA and IgM; occasionally proteins. Proteins are separated according demonstrated on the electrophoretogram IgG). This fraction can be with in amma- to their physical properties (size, mass in Figure 2 as the tallest band. tion, neoplasia and hepatic disease. Page 24 - VETcpd - Vol 4 - Issue 4.
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