Blood 2

Leukemia's continued

In all leukemias the red bone marrow becomes almost totally occupied by cancerous leukocytes and immature WBCs flood into the bloodstream. The other blood cell lines are crowded out, so severe anemia and bleeding problems also result. Other symptoms include fever, weight loss, and bone pain. Although tremendous numbers of leukocytes are produced, they are nonfunctional and cannot defend the body in the usual way. The most common causes of death are internal hemorrhage and overwhelming infections.

treatment of leukemia

Irradiation and administration of antileukemic drugs to destroy the rapidly dividing cells have successfully induced remissions (symptoms free periods) lasting from months to years. Stem cell transplants are used in selected patients when compatible donors are available.

most abundant to least abundant

Students are often asked to list the leukocytes in order from most abundent to least abundent. The following phrase may help you with this task: Never Let Monkeys Eat Bananas (neutrophils, lymphocytes, monocytes, eosinophils, basophils).

granulocyte storage

The bone marrow stores mature granulocytes and usually contains about 10 times more granulocytes than are found in the blood. The normal ratio of granulocytes to erythrocytes produced is about 3:1, which reflects the much short life span (0.25 to 9.0 days) of the granulocytes. Most die combating invading microorganisms.

Function of eosinophils

The most important role of eosinophils is to lead the counterattack against parasitic worms, such as flatworms (tapeworms and flukes) and roundworms (pinworms and hookworms) that are too large to be phagocytized. These worms are ingested in food (especially raw fish) or invade the body via the skin and then typically burrow into the intestinal or respiratory mucosae. Eosinophils reside in the loose connective tissues at the same body sites, and when they encounter a parasitic worm "prey", they gather around and release enzymes from their cytoplasmic granules onto the parasite's surface, digesting it away. Eosinophils have complex roles in many other diseases including allergy and asthma. While they contribute to the tissue damage that occurs in many immune processes, we are also beginning to recognize them as important modulators of the immune response.

Basophils

Basophils are the rarest of WBCs, averaging only 0.5-1% of the leukocyte population. Their cytoplasm contains large, coarse, histamine-containing granules that have an affinity for the basic dyes and stain purplish-black. Histamine is an inflammatory chemical that acts as a vasodilator (makes blood vessels dilate) and attracts other white blood cells to the inflamed site; drugs called antihistamines counter this effect. The deep purple nucleus is generally U or S shaped with one or two conspicuous constrictions.

Agranulocyte lineages

Despite their similar appearances, the 2 types of agranulocytes have very different lineages. Monocytes are derived from myeloid stem cells, and share a common precursor with neutrophils that is not shared with the other granulocytes. Cells following the monocyte line pass through the monoblast and promonocyte stages before leaving the bone marrow and becoming monocytes. Lymphocytes derive from the lymphoid stem cell and progress through the lymphoblast and prolymphocyte stages. The prolymphocytes lave the bone marrow and travel to the lymphoid tissues, where their further differentiation occurs. Monocytes may live for several months, whereas the life span of lymphocytes varies from a few hours to decades.

Eosinophils

Eosinophils account for 2-4% of all leukocytes and are approximately the size of neutrophils. Their deep red nucleus usually resembles an old-fashioned telephone receiver--it has 2 lobes connected by a broad band of nuclear material.

leukocyte production

Figure 17.11 shows the pathways of leukocyte differentiation, starting with the hematopoetic stem cell, or hemocytoblast, that rise to all of the formed elements in the blood. An early branching of the pathway divides the lymphoid stem cells, which produce lymphocytes, from the myeloid stem cells, which give rise to all other formed elements. In each granulocyte line, the committed cells, called myeloblasts, accumulate lysosomes becoming promyelocytes. The distinctive granules of each granuloctye type appear next in the myelocyte stage and then cell division stops. In the subsequent stage, the nuclei arc, producing the band cell stage. Just before granulocytes leave the marrow and enter the circulation, their nuclei constrict, beginning the process of nuclear segmentation.

use of EPO and CSF in clinical patients

Many of the hematopoietic hormones (EPO and several of the CSF's) are used clinically to stimulate bone marrow of cancer patients who are receiving chemotherapy (which suppresses the marrow) and of those who have recived stem cell transplants, and to beef up the protective responses of AIDS patients.

Monocytes

Monocytes account for 3-8% of WBCs. They have an average diameter of 18 um and are the largest leukocytes. They have abundant pale-blue cytoplasm and a darkly staining purple nucleus, which is distinctly U or kidney shaped

mononucleosis

Once called the kissing disease; infectious mononucleosis is a highly contagious viral disease most often seen in young adults. Caused by the Epstein-Barr virus, its hallmark is excessive numbers of agranulocytes, many of which are atypical. The affected individual complains of being tired and achy, and has a chronic sore throat and a low-grad fever. there is no cure, but rest the condition typically runs its course to recovery in a few weeks.

overproduction of abnormal leukocytes

Overproduction of abnormal leukocytes occurs in leukemia and infectious mononucleosis. At the opposite pole, leukopenia is an abnormally low WBC count. commonly induced by drugs, particularly glucocorticoids and anticancer agents.

Agranulocytes

The agranulocytes include lymphocytes and monocytes, WBCs that lack visible cytoplasmic granules. Although they are similar structurally, they are functionally distinct and unrelated cell types. Their nuclei are typically spherical or kidney shaped.

acute leukemia

The more serious acute forms primarily affect children. Chronic leukemia is seen more often in elderly people. Without therapy, all leukemias are fatal, and only the time course differs.

mast cells

Granulated cells similar to basophils, called mast cells, are found in connective tissue. Although mast cell nuclei tend to be more oval than lobed, the cells are similar microscopically, and both cell types bind to a particular antibody (immunoglobulin E) that causes the cells to release histamine. However, they arise from different cell lines.

Granulocytes

Granulocytes, which include neutrophils, basophils, and eosinophils, are all roughly spherical in shape. They are larger and much shorter lived (in most cases) than erythrocytes. They characteristically have lobed nuclei (rounded nuclear masses connected by thinner strands of nuclear material), and their membrane-bound cytoplasmic granules stain quite specifically with Wright's stain. Functionally, all granulocytes are phagocytes to a greater or lesser degree.

T lymphocytes and B lymphocytes

Large numbers of lymphocytes exist in the body, but only a small proportion of them (mostly small lymphocytes) are found in the bloodstream. In fact, lymphocytes are so called because most are closely associated with lymphoid tissues (lymph nodes, spleen, ect.), where they play a crucial role in immunity. T lymphocytes (T cells) function in the immune response by acting directly against virus-infected cells and tumor cells. B lymphocytes (B cells) give rise to plasma cells, which produce antibodies (immunoglobins) that are released to the blood.

Eosinophils continued

Large, coarse granules that stain from brick red to crimson with acid (eosin) dyes pack the cytoplasm. These granules are lysosome-like and filled with a unique variety of digestive enzymes. However, unlike typical lysosomes, they lack enzymes that specifically digest bacteria.

leukocytes and diapedesis

Leukocytes are crucial to our defense against disease. They form a mobile army that helps protect the body from damage by bacteria, viruses, parasites, toxins, and tumor cells. As such, they have some special functional characteristics. Red blood cells are confined to the bloodstream, and they carry out their functions in the blood. But white blood cells are able to slip out of the capillary blood vessels-- a process called diapedesis--and the circulatory system is simply their means of transport to areas of the body (mostly loose connective tissues or lymphoid tissues) where they are needed to mount inflammatory or immune response.

granulocytes and agranulocytes

Leukocytes are grouped into 2 major categories on the basis of structural and chemical characteristics. Granulocytes contain obvious membrane-bound cytoplasmic granules, and agranulocytes lack obvious granules

WBCs

Leukocytes, or white blood cells (WBCs), are the only formed elements that are complete cells, with nuclei and the usual organelles. Accounting for less than 1% of total blood volume, leukocytes are far less numerous than red blood cells. On average, there are 4800-10,800 WBCs/ul of blood.

Leukopoiesis- interleukins and CSFs

Like erythrocytes, leukopoiesis, or the production of white blood cells, is stimulated by chemical messengers. These messengers, which can act either as paracrines or hormones, are glycoproteins that fall into 2 families of hemotopoietic factors, interleukins and colony-stimulating factors, or CSFs. The interleukins are numbered (eg. IL-3, IL-5), but most CSFs are named for the leukocyte population they stimulate--for example, granulocyte-CSF (G-CSF) stimulates production of granulocytes. Hematopoietic factors, released by supporting cells of the red bone marrow are mature WBCs, not only prompt the white blood cell precursors to divide and mature, but also enhance the protective potency of mature leukocytes

Lymphocytes

Lymphocytes, accounting for 25% or more of the WBC population, are the second numerous leukocytes in the blood. When stained, a typical lymphocyte has a large, dark-purple nucleus that occupies most of the cell volume. The nucleus is usually spherical but may be slightly indented, and it is surrounded by a thin rim of pale-blue cytoplasm. Lymphocytes diameter ranges from 5 to 17 um, but they are often classified according to size as small (5-8 um), medium (10-12 um), and large (14-17 um).

polymorphonuclear leukocytes

Neutrophil nuclei consist of 3 to 6 lobes. Because of this nuclear variability, they are often called polymorphonuclear leukocytes (PMNs) or simply polys.

respiratory burst

Neutrophils are our body's bacteria slayers, and their numbers increase explosively during acute bacterial infection such as meningitis and appendicitis. Neurophils are chemically attracted to sites of inflammation and are active phagocytes. They are especially partial to bacteria and some fungi, and bacterial killing is promoted by a process called a respiratory burst. In the potent germ-killer oxidating substances such as bleach and hydrogen peroxide, and granules containing defensin-meditated lysis occurs. It appears that when the granules containing defensins are merged with a microbe-containing phagosome, the defensins form peptide "spears that pierce holes in the membrane of the ingested "foe".

Neutrophils

Neutrophils are the most numerous of the white blood cells, accounting for 50-70% of the WBC population. Neutrophils are about twice as large as erythrocytes.

defensins

The neutrophil cytoplasm stains pale lilac and contains very fine granules (of 2 varieties) that are difficult to see. They are called neutrophils because their granules take up both basis (blue) and acidic (red) dyes. Together, the 2 types of granules give the cytoplasm a lilac color. Some of these granules contain hydrolytic enzymes, and are regarded as lysosomes. Others, especially the smaller granules, contain a potent "brew" of antimicrobial proteins, called defensins.

amoeboid motion and positive chemotaxis

The signals that prompt the WBCs to leave the bloodstream at specific locations are cell adhesion molecules displayed by endothelial cells forming the capillary walls at sites of inflammation. Once out of the bloodstream, leukocytes move through the tissue spaces by amoeboid motion (they form flowing cytoplasmic extensions that move them along). By following the chemical trail of molecules released by damaged cells or other leukocytes, a phenomenon called positive chemotaxis, they can pinpoint areas of tissue damage and infection and gather there in largge numbers to destroy foreign substances or dead cells.

Leukemia

The term leukemia, literally "white blood cell", refers to a group of cancerous conditions involving white blood cells. As a rule, the renegade leukocytes are members of a single clone (descendents of a singe cell) that remain unspecialized and proliferate out of control, impairing normal red bone marrow function. The leukemias are named according to the abnormal cell type primarily involved. For example, myelocytic leukemia involves myeloblast descendents, whereas lymphocytic leukemia involves the lymphocytes. Leukemia is acute (quickly advancing) if it derives from blast-type cells like lymphoblasts, and chronic (slowly advancing) if it involves proliferation of later cell stages myelocytes.

Monocytes continued

When circulating monocytes leave he bloodstream and enter the tissues, they differentiate into highly mobile macrophages with prodigious appetites. Macrophages are actively phagocytic, and they are crucial in the body's defense against viruses, certain intracellular bacterial parasites, and chronic infections such as tuberculosis. Macrophages are also important in activating lymphocytes to mount the immune response.

leukocytosis

Whenever white blood cells are mobilized for action, the body speeds up their production and twice the normal number may appear in the blood within a few hours. A white blood cell count of over 11,000 cells/ul is leukocytosis. This condition is a normal homeostatic response to an infection in the body.