Top 5 Signs of Patient Stress & Excitement on Clinical Pathology

Evaluation of laboratory data for indicators of underlying disease is a mainstay of veterinary diagnostics. In addition to disease mechanisms, routine physiologic responses can also impact measured variables. A common example of an interpretive consideration is patient stress and/or excitement due to illness or unfamiliarity with the veterinary clinic.

Following are the author's top 5 signs of patient stress and excitement on clinical pathology.

1. Stress Leukogram

A stress leukogram is a common set of leukocyte responses caused by the release of endogenous corticosteroids that result from stress-related disease and hospitalization. Possible changes include segmented neutrophilia, lymphopenia, monocytosis, and eosinopenia, but all abnormalities are not always present,¹ and it is unusual for alterations to vary >2 to 3 times the reference values.² Lymphopenia is most common, and segmented neutrophilia is usually present.³ Monocytosis and eosinopenia are possible in dogs; however, they are more variable and frequently not present in cats. 

Neutrophilia is caused by decreased adherence to the vascular endothelium from receptor downregulation, which inhibits margination of cells and therefore increases the proportion of cells in the circulating pool inside blood vessels.⁴ Prolonged circulation time may cause neutrophils to appear hypersegmented,⁵ and increased release of neutrophils from bone marrow is possible.⁴ The segmented neutrophil count can double in dogs and triple in cats due to a larger number of cells in the marginating pool.⁶ Neither a left shift to band neutrophils or toxic changes are expected due to lack of inflammatory response.

Instead of entering circulation, lymphocytes become redistributed to and retained in lymphocytic tissue (eg, lymph nodes).⁶ It is suspected that monocytes increase in concentration due to mechanisms similar to those of neutrophils (eg, decreased margination), although this has not been definitively proven. Eosinopenia can be difficult to detect because eosinophils are rare and only a few may be present in circulation at baseline. 

The stress leukogram is transient, and cell dynamics return to normal when increased stress is resolved.³ The changes observed in a stress leukogram can also occur with consistently increased cortisol concentrations in patients with hyperadrenocorticism. Stressed patients with underlying illness may have a co-occurring inflammatory leukogram as suggested by the presence of a left shift and neutrophil toxicity; these do not occur with a stress response alone.

2. Physiologic Leukocytosis

Leukocytosis can be caused by fear, exercise, or excitement; is mediated by increased catecholamine concentrations (eg, epinephrine, norepinephrine); and should be considered a transient physiologic response. Catecholamine hormones can cause cells from the marginating pool to shift to the circulating pool in the vasculature.^5,7 This effect may double the total WBC concentration within minutes but is temporary, and, at least in horses, cell counts return to baseline values after 30 minutes.⁸ In addition, splenic contraction induced by catecholamine hormones can expel leukocytes into the peripheral circulation. 

Leukocytosis is usually characterized by segmented neutrophilia without a left shift. Lymphocytosis may be present, especially in kittens and young cats. The effect in cats is often considered a prominent lymphocytosis, which can be up to twice the upper reference value.^5,6

3. Erythrocytosis

Transient erythrocytosis occurs when catecholamines from excitement or stress cause splenic contraction, resulting in expulsion of stored erythrocytes into circulation.⁹ Transient erythrocytosis is most common in young horses, less frequent in dogs, and unusual in cats—possibly because the feline spleen is nonsinusoidal—but can occur under experimental conditions.^5,10 RBC concentration (ie, hematocrit) only slightly increases in most small animals, and the effect may not be appreciated because values may remain within reference intervals. In a study, the hematocrit of racing greyhounds increased immediately postrace, presumably due to catecholamine-induced splenic contraction, although decreased plasma volume may have also been a contributing factor.¹¹

4. Hyperglycemia

Transient stress hyperglycemia, or physiologic hyperglycemia, is particularly common in cats and is most likely due to catecholamine release in acute cases, resulting in glycogenolysis and suppression of insulin release.¹² An increase in glucose and lactate concentrations has been correlated with epinephrine and norepinephrine, but not cortisol, concentrations.¹² 

Stress hyperglycemia should be differentiated from diabetes mellitus, but this can be challenging, especially in cats, as blood glucose can become increased with stress alone. Diabetes mellitus is unlikely if repeat sampling for hyperglycemia is negative. In patients with chronic stress, endogenous corticosteroids may be more likely to cause hyperglycemia.¹³ Catecholamines and corticosteroids can be contributing factors for transient hyperglycemia in hospitalized patients. 

Measuring fructosamine concentration can also help discern stress-related hyperglycemia from diabetes mellitus.¹⁴ In dogs, infusion of a combination of glucagon, epinephrine, and cortisol (ie, stress hormones) more effectively induced hyperglycemia than individual hormones.¹⁵ Glucosuria may occur with stress-related hyperglycemia, particularly in cats, if the renal threshold is exceeded.

5. Increased Corticosteroid-Induced ALP Activity

Chronic stress in dogs can cause long-term increase of endogenous corticosteroids, which may result in increases in serum ALP activity. Increased activity is initially due to an increase in the liver ALP isoenzyme; corticosteroid-induced ALP (C-ALP) activity begins to increase after 7 days.¹⁶ Evidence indicates that hepatocytes upregulate a gene that generates C-ALP when exposed to corticosteroids.¹⁷ Cats do not have C-ALP. 

Enzymatic activity may remain increased for several weeks after stress has resolved due to the prolonged half-life of the hormones. C-ALP activity can be used to screen for hyperadrenocorticism, but screening can be challenging in stressed patients. Although C-ALP can be measured specifically, only total ALP activity is typically reported. It is thus important to consider the impact of stress when investigating liver disease.¹⁸

Conclusion

Patient stress and excitement may interfere with routine laboratory data interpretation. It is important to consider these factors so the most accurate conclusions are drawn and the patient is managed appropriately.