| THE ACUTE PHASE RESPONSE AND C-REACTIVE PROTEIN (CRP)
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| The acute phase response is a nonspecific response to tissue injury or infection; it affects several organs and tissues
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| During the acute phase response, there is a characteristic pattern of change in certain proteins-in particular, a marked increase in the synthesis of some proteins (predominantly in the liver), along with a decrease in the plasma concentration of some others (Fig. 3.8). An increase in the synthesis of proteins such as proteinase inhibitors (α1-antitrypsin), coagulation proteins (fibrinogen, prothrombin), complement proteins, and CRP is of obvious clinical benefit (Fig. 3.9). The synthesis of albumin, transthyretin (prealbumin), and transferrin decreases during the acute phase response, and they are thus termed the 'negative acute phase reactants'.
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| CRP is a major component of the acute phase response and a marker of bacterial infection. It is synthesized in the liver and is constructed of five polypeptide subunits, having a molecular weight of around 130 kDa. It is present in only minute quantities (<1 mg/L in normal serum) and is believed to mediate binding of foreign polysaccharides, phospholipids, and complex polyanions, and also activating complement via the classical pathway (see Chapter 36).
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| Figure 3.7 Comparison of gel electrophoretic appearance of normal serum and that containing monoclonal immunoglobulins. The scanning pattern peaks (solid line) represent the relative concentrations of the separated proteins. (A) Normal serum. (B) Monoclonal gammopathy: a strongly stained band is present in the γ-globulin region on electrophoresis, and there is an associated reduction of staining in the remainder of the γ-region (immunoparesis). |
| Figure 3.8 Acute phase response. Gel electrophoretic pattern observed in serum during the acute phase response. Albumin is decreased, the sum of α1- and α2-globulins is increased, β1-globulins are decreased, β2-globulins are increased and there is a mild increase in γ-globulins. |
| Figure 3.9 C-reactive protein (CRP) and the post-operative acute phase reaction. The concentration of CRP increases as part of the acute phase response to surgical trauma, and a further increase may be observed if recovery is complicated by infection. (The dotted line represents response to uncomplicated surgery). |
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| A 45-year-old woman suffered severe lower limb injuries in a road traffic accident. After her admission to hospital, biochemical profiling revealed slightly decreased concentrations of total serum protein (58 g/L) (normal 63-86 g/L) and serum albumin (35 g/L) (normal 35-45 g/L). Serum electrophoresis revealed an increase in the α1 and α2 protein fractions. Four days after her operation, the patient's condition deteriorated, and she developed an increased temperature, sweating, and confusion. An acute infection was diagnosed and treatment with appropriate antibiotics was commenced. CRP concentrations peaked 5 days after the operation (Fig. 3.9). |
| Comment. Increased concentrations of α1 and α2 proteins (which include α1-antitrypsin, α1-acid glycoprotein, and haptoglobin), together with a decrease in serum albumin concentration, suggest an acute phase response. This response is also associated with an increase in CRP, the erythrocyte sedimentation rate (ESR), and increased plasma viscosity. A therapeutic response to treatment of infection can be assessed by a decrease in plasma CRP concentration. |
| Using assay for CRP, which is approximately a hundred times more sensitive than the conventional CRP measurement method, one may detect minimal fluctuations in the concentration of this protein. Interestingly, very small increases in CRP concentration, much smaller than those seen in an acute infection, seem to indicate a state of
chronic-low-grade inflammation which is associated, for instance, with an increased risk of heart disease (see Chapter 42). Other inflammatory conditions such as inflammatory bowel disorders, type 2 diabetes and the metabolic syndrome (see Chapter 20). Abdominal aortic aneurysm and premature rupture of membranes during pregnancy have also been associated with these minute increases in serum CRP concentration.
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