Chapter 38 Inflammation in Marine Mammals
The most common illnesses affecting marine mammals result from infectious agents that cause inflammation. Similarly, a number of less common, noninfectious diseases are equally capable of eliciting similar levels of inflammation. Armed with these clues, the clinician must be able to identify a morbid individual within a group of animals who are adept at masking clinical signs of illness. Frequently, blood samples are taken from suspicious individuals and judgments are made based on seemingly insignificant changes in hematologic and biochemical values.
This chapter defines the hallmark changes in clinical pathology indicative of inflammation and provides several new insights in identifying individual marine animals that might otherwise remain undetected.
Currently, the most reliable tests that indicate the presence of inflammation are white blood cell (WBC) counts, including differential counts and reticulocyte counts; hemoglobin or packed cell volume; fibrinogen; erythrocyte sedimentation rate; albumin; alkaline phosphatase; and iron.8,10 Almost all these tests are affected variably by all known inflammatory diseases of marine mammals.
Most of us as clinical veterinarians are familiar with total WBC and differential counts because they change with infection and the resulting inflammation. In an effort to detect early onset of inflammation more closely, we have redefined the criteria for “band” neutrophils. Rather than the more conventional definition (i.e., cells with pinched filaments >50% of filament diameter), we count any neutrophil with chromatin spanning the lobules as a band.
The reason for this new definition is simple. Although we use other indicators to make a diagnosis of inflammation, our goal is not to miss individuals who are in early stages of band production and not experiencing an obvious left shift. In the past we would have overlooked this early cell, so by redefining bands, we now observe 2% to 5% in normal individuals. By using the more conventional definition for bands, we would more likely miss early subclinical individuals. As with other inflammatory parameters, the astute clinician should weigh the importance of this finding with other changes in clinical pathology and in concert with the history and physical examination. The fundamental goal is to avoid the surprise of finding a significant change in the percentages of bands when a second blood sample is taken shortly after the first.
For the vast majority of marine mammal cases involving acute inflammation, hemoglobin (Hb) and packed cell volume (PCV) decrease an average of 7% to 10%. The reason is not entirely understood, but fluid shifts in response to the release of inflammatory mediators are presumably involved, rather than an actual blood loss. Once the inflammatory nidus is controlled, these parameters return to normal, generally without evidence of a regenerative hemogram. If, on the other hand, Hb and PCV slowly drop to subnormal levels, in the absence of responsiveness (i.e., PCV, mean cell volume, and reticulocyte counts increase, and polychromatic cells appear), anemia of chronic disease (ACD) is most likely, again rather than blood loss.
In animals with chronic inflammation and low-grade anemia, reticulocyte counts generally drop, most likely because of decreased red blood cell (RBC) regeneration. This must be distinguished from blood loss anemia, in which reticulocyte counts rise above normal while Hb and PCV continue to drop. As with other subjective tests (e.g., differential count), values for normal reticulocyte numbers must come from marine mammals under the veterinarian’s care.8
In my experience, plasma fibrinogen is the most reliable indicator of inflammation as long as the test is quantitative and not qualitative (as with heat precipitation methods). Some clinicians believe fibrinogen correlates directly with erythrocyte sedimentation rate (ESR); in my experience, however, variable effects are seen. In fact, fibrinogen levels are almost always elevated when the ESR is increased, but the converse is frequently not true. This is especially evident with dehydrated patients, in which increased viscosity slows the sedimentation of RBCs, but has little or no effect on the concentration of fibrinogen.
Serum albumin levels usually drop below normal from the direct effect of inflammatory mediators on the synthesis of messenger ribonucleic acid (mRNA) in the liver.13,14 The drop normally follows a rise in fibrinogen, which is rarely as dramatic; however, a 10% to 20% decline is expected with presence of inflammation. Globulin levels normally remain unchanged in the early stages of infections and generally increase if the process becomes chronic.
Serum alkaline phosphatase (ALP) levels vary with age, nutritional status, and presence of infection or inflammation. In cetaceans, ALP is extremely high early in life because of intense bone remodeling, and only malnutrition, inflammation, and infectious agents may reduce these levels. Even older individuals with significantly lower baseline levels, weight loss or gain, or extrahepatic infection may produce a corresponding increase and decease in levels of ALP. As with serum albumin, synthesis of mRNA in the liver appears to be sensitive to these effects. Unlike in most other mammals, ALP in marine mammals is not affected to the same extent as alanine transaminase (AST), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), and lactate dehydrogenase (LDH) in inflammatory hepatic diseases.
During an acute phase of a bacterial infection, serum iron may drop rapidly and rather dramatically. Iron is sequestered by iron-binding proteins and temporarily stored in the liver, rendering it unavailable for invading bacterial pathogens. Acute-phase proteins (e.g., interleukin-1, C-reactive protein, prostaglandins, tumor necrosis factor, interferon) help mediate this iron sequestration.2 The opposite is true of hepatocellular bacterial infections and even some noninfectious diseases, such as hemochromatosis, lipidosis, and azole hepatopathies, in which iron is liberated from the liver and into the serum.10 Trends in serum iron levels are important when evaluating clinical condition and prognosis, although changes in magnitude do not appear to correlate directly with severity.