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Date posted: November 29, 2011

Dr.Sreekumar.A

Leucocytes -Its Development, Functions, Normal Values, Variations.
Leucocytes or white blood cells have an important function in defending the body cells against the microbes and other foreign materials. Leucocytes are the largest blood cells and they account for about 1% of the blood volume. Most of the leucocytes are outside the circulation, and few in the bloodstream are in transit from one site to another. They are of two types.

1) Granulocytes
The term granulocyte is due to the presence of granules in the cytoplasm of these cells. In the different types of granulocytes, the granules are different which help us to distinguish them. In fact, these granules have a different affinity towards neutral, acid or basic stains and give the cytoplasm different colors. So, granulocytes distinguish themselves into Europhile (purple as they take both dyes), eosinophil or acidophil (take red in acid dye eosin) and basophil (alkaline dye methyelene blue).

2) Lymphoid cells or agranulocytes
The lymphoid cells are lymphocytes and monocytes. They have a large nucleus and have no granules in their cytoplasm.

Formation of White blood Cells

  • Haemopoetic cells are seen in yolk sac of a 2 week embryo. By 8 weeks haemopoesis gets established in liver. By 12-16 weeks, liver becomes the major site and continues to be active until a few weeks before birth.
  • During this period spleen is also active in lymphoid cell production. Also foetal thymus is a transient site for few lymphocytes in this period. By 20 weeks of gestation bone marrow becomes active. 
  • At birth red marrow occupies the entire capacity of bone. and continues so for 2-3 years 
  • Within 10 weeks of birth marrow becomes the major site of haemopoesis.Gradually red marrow is replaced by inactive, fatty, yellow lymphoid marrow. 
  • By 20-22 years red marrow is present only in the flat bones and upper ends of femur and humerus. 
  • However, because of the growth in body and bone size that has occurred during this period, the total amount of active red marrow (approximately 1000-1500 g) is nearly identical in the child and the adult.
  • About two-thirds of the marrow mass, functions in white cell production (leucopoiesis), and one-third in red cell production (erythropoiesis). However there are approximately 700 times as many red cells as white cells in peripheral blood. This apparent anomaly reflects the shorter life span and hence greater turnover of the white blood cells in comparison with the red blood cells.

It is now generally accepted that all blood cells are made from a relatively few ‘uncommitted’ cells which are capable of mitosis and of differentiation into ‘committed’ precursors of each of the main types of blood cell.  

LEUCOCYTES

Unlike red cells, leukocytes have a nucleus. It is easily visible under the microscope, but only after having stained the smear. The nucleus of these cells can show multiple lobes, or be indented or kidney-shaped (reniform). Usually, the shape of the nucleus of various kinds of leukocytes is different. Together with the different colors of granules, the shape of nucleus helps us to recognize these cells. Leukocytes are divided into granulocytes and lymphoid cells. In the drawings which follow, besides nuclei and granules, you can see even mitochondria, Golgi apparatus, endoplasmic reticula and ribosomes.

The neutrophil are the more common leukocytes. They have a diameter of 12-15 µm. You can recognize them as their nucleus is divided into 2 – 5 lobes connected by a fine nuclear strand or filament. The cytoplasm is transparent because its granules are small and purple as they take both dyes. In the nucleus of the neutrophil of cells from females, you may see an appendage like a little drumstick. It is the second X chromosome, inactivated.

Normally the eosinophils are quite rare in the blood and have the same size as the neutrophils.Generally nucleus is bi-lobed. But even nuclei with three or four lobes have been observed. The cytoplasm is full of large angular granules which assume a characteristic pink-orange color as they take acid stain-eosin.

Basophils are the rarest leukocytes: less than 1 %. They are quite small: 9-10 µm in diameter. Cytoplasm is very rich in large granules which take a dark purple color due to the alkaline dye methylene blue. The granules contain histamine and heparin. The nucleus is bi- or tri-lobed, but it is hard to see because of the number of granules which hide it.

LYMPHOID CELLS (or agranulocytes)

 They have a compact nucleus and a transparent cytoplasm.

Lymphocytes are quite common in the blood: 20-40%, 8-10 µm in diameter and generally they are smaller than the other leukocytes but they are still a few larger than red cells. The cytoplasm is transparent. The nucleus is round and large in comparison to the cell and it occupies most of it. In any case, some of the cytoplasm remains visible, generally in a lateral position. According to the quantity of cytoplasm, lymphocytes are divided into small, medium and large.

Monocytes are the biggest leukocytes: 16-20 µm. They have a great reniform or horseshoe-shaped nucleus, in some cases even bi-lobed. The cytoplasm is transparent, but with an appearance of “ground glass”. 

Functions

Neutrophils- Prime function of which is to ingest and kill bacteria, fungi and damaged cells.Neutrophils are attracted to sites of infection or inflammation by chemotaxins.Recognition of foreign or dead material is aided by coating of particles with immunoglobulin and compliment as neutrophils have their receptors. The material is ingested into vacuoles where it is subjected to enzymic destruction.

Eosinophils- Play an important role in allergic responses and in the defense against infections with helminthes and protozoa.

Basophil secretes anti-coagulant and vasodilatory substances as histamines and serotonin. Even if they have a phagocytory capability, their main function is secreting substances which mediate the hypersensitivity reaction.

Lymphocytes are cells which, besides being present in the blood, populate the lymphoid tissues and organs too, as well as the lymph circulating in the lymphatic vessel. The lymphoid organs include thymus, bone marrow (in bird’s bursa), spleen, lymphoid nodules, palatine tonsils, Peyer’s patches and lymphoid tissue of respiratory and gastrointestinal tracts.

Most lymphocytes circulating in the blood is in a resting state. They look like little cells with a compact round nucleus which occupies nearly all the cellular volume. As a consequence, the cytoplasm is much reduced. The lymphocytes of the lymphoid tissues and organs can be activated in a different amount following antigenic stimulation.

The cells of the immune system, chiefly lymphocytes, cooperate amongst themselves to activate, boost or make more precise the immune response. To attain this scope, there exist different types of lymphocytes, with different functions: T and B lymphocytes.

T-Lymphocytes processed by the thymus gland provide cell-mediated immunity. It is programmed to recognize only one type of antigen. In their turn, the T cells are divided into three categories: Tc (cytotoxic), Th (helpers), Ts (suppressors).

 Cytotoxic lymphocytes breed quickly when they are activated. They do not release antibodies in the bloodstream, but they keep the antibodies on their membrane and use them to recognize cells. The cytotoxic lymphocytes kill cells by means of osmotic lysis (cell-mediated response).

The helper lymphocytes are needed to activate both B and Tc lymphocytes which, even though they recognize extraneous agents, seldom enter into direct action.

Suppressor lymphocytes reduce the intensity of the immune response.

B-Lymphocytes are processed in the bone marrow. They produce anti bodies or immunoglobulin which are proteins designed to bind and cause the destruction of of antigen. They thus provide antibody mediated or humoral immunity. When the B cells are activated, they breed quickly (clonal selection) and they become plasma cells which secrete a great deal of antibodies in the blood stream (humoral response).

Monocytes are the precursors of macrophages. The monocytes – Macrophage system is sometimes called the reticuloendothelial system. They are larger blood cells, which after attaining maturity in the bone marrow, enter the blood circulation where they stay for 24-36 hours. Then they migrate into the connective tissue, where they become macrophages and move within the tissues. In the presence of an inflammation site, monocytes quickly migrate from the blood vessel and start an intense phagocytory activity. The role of these cells is not solely in phagocytosis because they have also had an intense secretory activity. They produce substances which have defensive functions such as lysozyme, interferons, cytokines and other substances which modulate the functionality of other cells. Macrophages cooperate in the immune defense. They expose molecules of digested bodies on the membrane and present them to more specialized cells, such as B and Th lymphocytes. 

Normal Values:

Total count –        4,000 to 11,000 per mm3

                                             4.0 to 11.0 x 109 /l

Each type of leukocyte is present in the blood in different proportions. In the child up to the age of 7years, Lymphocytes are the predominant white cell type but after the age of 7 neutrophils is the most predominant type.

Neutrophil     50 – 70 %          (2.5 to 7.5 x 109/l)
Eosinophil     2 – 4 %              (0.04 to 0.44 x 109/l)
Basophil        0.5 – 1 %           (0.015 to 0.1 x 109/l)
Lymphocyte 20 – 40 %            (1.5     to 3.5 x 109/l)
Monocytes      3 – 8 %             (0.2 to 0.8 x 109/l)

Absolute Eosinophil Count – The number of eosinophil cells in a given area per 100 cells is counted. The percentage of eosinophil is multiplied by the wbc count   give the absolute eosinophil count. – Less than 350 cells/mol. 

Variations: 

1) Leucopenia – When total leukocyte count is less than 4000/cu.mm

a.     Granulocytopenia – General term used to indicate an abnormal reduction in the number of circulating granulocytes commonly called Neutropenia because 40  to 75% of granulocytes are neutrophils.Neutrophils less than 1500/ml.

Causes –

  • Congenital -(Kostmann’s syndrome)
  • Racial – common in Black races
  • Infection -  viral, bacterial(typhoid)
  • Felty’s syndrome
  • Auto immune Neutropenia
  • Pancytopenia – marrow aplasia
  • Genetic cyclic Neutropenia every 2-3 weeks

b. Agranulocytosis – Extreme shortage or absence of granulocytes.

2) Leucocytosis – When total leucocyte count is more than   11,000/cu.mm.With any tissue necrosis there is a release of various soluble factors, causing leucocytosis.

Neutrophil leucocytosis – greater than 10,000/cu.mm

  • Bacterial infections
  • Tissue necrosis
  • Myocardial infarction
  • Trauma
  • Drugs
  • Corticosteroids
  • Lithium

        Hematological

  • Myeloproliferative disease
  • Leukaemoid reaction
  • Leucoerythroblastic anaemia

        Physiological

  • Pregnancy
  • Exercise
  • Malignant diseases
  • Metabolic
  • Renal failure, acidosis.

Eosinophilia – greater than 4,000/cu.mm

· Parasitic infestations

o   Ascaris,Hookworm,Strongyloides

· Allergic disorders

o   Hay fever,Hypersensitivity reactions

· Skin disorders

o   Pemphigus,Eczema,Urticaria

· Pulmonary disorders

o   Bronchial asthma

o   Tropical pulmonary eosinophilia

o   Allergic bronchopulmonary aspergillosis

·        Malignant disorders

o   Hodgkin’s disease

o   Carcinoma

o   Eosinophilic leukemia

·   Miscellaneous

o   Sarcoidosis

o   Hypoadrenalism

o   Eosinophilic gastroenteritis

Basophils – Usually few but are significantly increased in myeloproliferative disorders like PV,CML,ET.

 Lymphocytosis – greater than 5,000/cu.mm occurs in response to

· Viral infections

o   EBV,CMV,HIV

· Chronic infections

o   TB,Toxoplasmosis

· Chronic lymphocytic leukemia

· Lymphomas

Monocytosis – greater than 800/cu.mm may be seen in

·  chronic bacterial infections such as

o   tuberculosis

o   infective endocarditis

· Chronic neutropenia

· Patients with myelodysplasia

Other variations-

  • Toxic granulation – When granule staining becomes more intense in response to infection.
  • Right shift – In megaloblastic or iron deficiency anemia six or more nuclear segments appear in neutrophils.
  • Immature neutrophils have a band-shaped or horse shoe-shaped nucleus and are known as band cells.
  • Leucoerythroblastic picture – Appearance of more primitive myeloid precursors in blood associated with presence of nucleated red cells.
  • Leukemia – Is a malignant proliferation of white blood cell precursors by the bone marrow which results in uncontrolled increase in the production of leucocytes and/or their precursors.

Homoeopathic Actions 

1) IODUM (William Boericke)
Iodine arouses the defensive apparatus of the system by assembling the mononuclear leucocytes whose phagocytic action is marked, at a given point.

2) Natr sulph (Clarke) :Nat.sul. withdraws water from the superannuated leucocytes, and thus causes their destruction.  The latter salt is, therefore a remedy for leukemia.

3) X-RAY :A general suppression of all cellular elements of blood except the heterophile leucocytes which increases.

4) ARSENICUM ALBUM (Neatby) :The red corpuscles and leucocytes of the blood are decreased in numbers.

5) CINCHONA : PATHOGENESIS the leucocytes soon become spheroidal and motionless in contact with a solution of quinine.

6) COLCHICUM (Neatby) : The polynuclear leucocytes are first collected in the marrow and tissues, but later they are greatly increased in the blood

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