Chapter 4

Leukocyte Function and Clinical Interpretation

 

 

                    

4.1 Required reading assignments:

Schalm's Veterinary Hematology - Jain

4.2 Objectives and/or study questions:

Students should be able to perform the following tasks upon completion of this section:

4.3 INTRODUCTION

Now that you have examined the erythrocytes and have a good understanding about their origin and function in health and disease, let us now examined the leukocytes. The total number of leukocytes present in the blood is far less than that of erythrocytes. This total number varies with species and with physiologic and pathologic states of individuals of the same species. Factors such as stress, exercise, feeding and age can cause great fluctuations in total leukocyte count. To account for normal variation in the total WBC count, the number of leukocytes per microliter of blood for a particular species is presented as a range. The generally accepted ranges for the domestic species are listed in the table of normal values located in the appendix of this syllabus. 

4.4 GENERAL CONSIDERATIONS

The term "Leukocyte" includes all white blood cells and their precursors. The granulocytes - neutrophils, eosinophils, and basophils - have their origin in bone marrow. Lymphocytes are produced in the spleen, lymph nodes, and lymphocytic foci scattered throughout the body. The origin of the monocyte is debatable, but its phagocytic potentialities point to the reticuloendothelial system as a most likely source. The leukocytes use the blood stream as a means of transport from point of origin to their destination in tissues. 

4.5 FUNCTIONS OF THE LEUKOCYTES

Leukocytes function as a first line of defense against foreign protein entering the body.

4.5.1 NEUTROPHILS

Neutrophils are the most active leukocytes in the initial stages of inflammation. In severe infections, immature forms of neutrophils, namely, myelocytes, metamyelocytes, and band neutrophils, may appear in peripheral blood; this is referred to as a "shift to the left." The neutrophils destroy bacteria, especially the cocci forms, by phagocytosis.

4.5.2 EOSINOPHILS

Eosinophils are found at the port of entry of foreign materials, that is, in the gut wall, subcutis, and lining of the respiratory tract. They accumulate at the site of antigen-antibody reactions and they inactivate histamine or histamine-like toxic materials. They increase in situations involving decomposition of body protein and this may reflect a function of detoxification.

4.5.3 LYMPHOCYTES

4.5.4 MONOCYTES

Monocytes are macrophages and their special enzyme systems are called upon to handle difficult pathogens, such as, fungi, protozoa, and tubercle bacilli. They digest tissue debris. Monocytosis indicates chronicity of the inflammatory process or infection with higher bacteria or fungi.

4.5.5 BASOPHILS

4.6 TOTAL LEUKOCYTE COUNT

The total white blood cell count is essential if one is to determine if there has been an increase or decrease in the number of leukocytes in circulation. The total white blood cell count varies from one species to another.

An increase in the total white blood cell count above the normal range is referred to as a leukocytosis. The leukocytosis is most frequently due to an increase in neutrophils, although, it may on occasions be due to an increase in one of the other main types. The total white cell count is elevated due to excitement, especially in the cat and horse (physiologic). Therefore, specimen should be obtained when the animal is calm.

A decrease in the total white blood cell count below the normal range in a given species is referred to as a leukopenia. A leukopenia is often associated with viral diseases but may be the result of an overwhelming bacterial infection or bone marrow exhaustion. In addition, numerous drugs and chemicals have been associated with a leukopenia (chloramphenicol, sulfonamide). An important point to remember here is that the bovine will show a leukopenia in acute bacterial infection such as acute mastitis. 

4.7 INCREASES IN THE LEUKOCYTES

An increase in a particular cell type may be associated with a number of diseases and/or conditions to include the following:

4.7.1 NEUTROPHILIA

4.7.2 EOSINOPHILIA

4.7.3 LYMPHOCYTOSIS

4.7.4 MONOCYTOSIS

4.7.5 BASOPHILIA

4.8 DIFFERENTIAL LEUKOCYTE COUNT

The stained blood smear is examined under the microscope to determine the relative number of the various types of leukocytes. This is essential if one is to determine which type of leukocyte has increased. In order to do the differential, at least one hundred leukocytes are observed and classified according to type. The results are recorded as the percent of the total which each type represents.

4.8.1 TYPES OF LEUKOCYTES TO BE EXPECTED

4.8.2 RELATIVE VS ABSOLUTE DIFFERENTIAL COUNTS

When the differential count is reported as the percentage of each cell type which makes up the total, it is called a "relative differential count".

The absolute differential count cannot be misinterpreted the way the relative count can. It consists of representing the various cell types according to the actual number of each type which is in the blood.

Serious misinterpretations may result when one uses the relative differential count alone for diagnostic purposes. Let us consider this analogy:

If we have 75 white balls and 25 black balls in a jar; 75% of the balls are white, 25% are black. Then if we take away 50 white balls, we have 25 of each type left or 50% of each. The black balls changed from 25% to 50% of the total even though there was no change in their number. Whenever there is a significant change in one cell type in the differential, there will always be an opposite change in the percentage of the other cells too, even though they did not really change in number at all.

To determine the absolute count, one multiplies the total count by the percentage of each type which is present. 

Example:

Total white count = 10,000/ul

Mature Neutrophils = 75%

Lymphocytes = 25%

The absolute count of neutrophils is 10,000 x 75% = 7500/ul The absolute count of lymphocytes is 10,000 x 25% = 2500/ul

The following example should indicate the misinterpretation that results from inspection of only the relative differential count:

NORMAL

Neutrophils 80% 60-77%

Lymphocytes 5% 12-30%

Eosinophils 15% 21-10%

Quick inspection of the differential suggests that this dog has a neutrophilia, a lymphopenia, and an eosinophilia. Can all of this be true?

The total white count is 4000/ul. Knowing this may give us some different ideas but will probably just confuse the issue.

Absolute differential count on this patient:

NORMAL

Neutrophils 80% x 4000/ul =3200 3,000-11,000

Lymphocytes 5% x 4000/ul = 200 1,000- 4,800

Eosinophils 15% x 4000/ul = 600 100- 1,250

Interpretation:

In terms of actual numbers of cells, the following has occurred:

4.9 THE EFFECTS OF GLUCOCORTICOID HORMONES ON THE HEMOGRAM

The administration of these steroids to animals induces a marked change in the leukogram (leukocyte blood picture). These changes include:

4.10 EFFECTS OF CORTICOSTERIODS HORMONES ON LEUKOCYTES

The release of ACTH from the pituitary under conditions of stress and disease, stimulates the release of corticosteriods from the adrenal gland. Leukocyte responses under conditions of stress are characterized by a leukocytosis with a neutrophilia, eosinopenia, and lymphopenia. A monocytosis may be observed in the dog and cow. The hemogram of animals being treated with steroids may be misinterpreted when the effects due to the drug are not understood. The following changes were observed in the hemograms of animals given ACTH intra-muscularly:

4.10.1 DOG

4.10.2 HORSE

4.10.3 CAT

4.10.4 COW

The increase in total leukocytes is due to an increase in the output of mature neutrophils from bone marrow storage and maturation pool and a decrease in the output of these cells from the blood stream. 

4.11 LEUKOCYTES IN DISEASE 

4.11.1 GENERAL CONSIDERATIONS

When antigen injures tissue cells, chemical substances are released which initiate and perpetuate the inflammatory reaction. Leukotaxine increases capillary permeability and, by chemotaxis, it attracts neutrophils into the area of injured cells. A leukocytosis-promoting factor, also produced from injured cells, is carried by the blood stream to the bone marrow where it stimulates granulopoiesis, thereby increasing the supply of neutrophils. In development of a severe inflammatory response, the need for neutrophils in large numbers is immediate. A neutrophil maturation and storage pool" exists in the bone marrow to meet the initial demand, whereas production of new neutrophils requires two to three days from the time of initial stimulus. Mature neutrophils are preferentially released over band cells from the maturation and storage pool into the peripheral blood. When the need for neutrophils exceeds the ability of bone marrow to supply that need in the form of mature neutrophils, then immature forms (band, metamyelocytes, etc.) are released to peripheral blood. Thus, the intensity of a disease process may be gauged by the extent of the shift to the left. 

4.11.2 CLASSIFICATION OF THE LEUKOCYTE RESPONSE

The ability of the bone marrow to respond to a bacterial infection is measured by the magnitude of the total leukocyte count; the intensity of the response is gauged by the extent of the left shift.

4.11.2.1 REGENERATIVE LEFT SHIFT

Characterized by a leukocytosis due to a neutrophilia with the appearance of immature granulocytes in peripheral blood.

  • 1. A slight left shift is limited to the occurrence of band neutrophils.
  • 2. A moderate left shift includes both band and metamyelocytes.
  • 3. A marked left shift includes myelocytes and progranulocytes.

4.11.2.2 DEGENERATIVE LEFT SHIFT

The total leukocyte count remains in the normal range or is only slightly elevated, while the immature granulocytes are markedly increased.

  • 1. It reflects the inability of the bone marrow to response to the infection.
  • 2. It is commonly seen in bacterial infection with septicemia.

4.11.2.3 LEUKOMOID BLOOD PICTURE

Similar to a regenerative left shift except the total white count is extremely elevated suggesting a granulocytic leukemia.

  • 1. The process stimulating the count is other than leukemia.
  • 2. A leukemoid hemogram may be seen in pyometra of the dog, abscess formation, severe hemorrhage or hemolytic crisis. 

4.11.3 TOXIC CHANGES IN NEUTROPHILS

The severity of the infection is measured by the occurrence of toxic changes in the neutrophils. The following are recognized as manifestations of toxicity: