OpenStax blood_lecture 22
The Cardiovascular System: Blood
Introduction
A single drop of blood contains millions of red blood cells, white blood cells, and platelets.
Chapter Objectives:
Identify the primary functions of blood, its fluid and cellular components, and its physical characteristics.
Identify the most important proteins and other solutes present in blood plasma.
Describe the formation of the formed element components of blood.
Discuss the structure and function of red blood cells and hemoglobin.
Classify and characterize white blood cells.
Describe the structure of platelets and explain the process of hemostasis.
Explain the significance of AB and Rh blood groups in blood transfusions.
Discuss a variety of blood disorders.
Overview of Blood
Single-celled organisms obtain nutrients directly and excrete wastes directly into their environment, thus they do not need blood.
Humans need blood to deliver nutrients to and remove wastes from trillions of cells.
The heart pumps blood throughout the body in a network of blood vessels.
The cardiovascular system is comprised of blood, the heart, and blood vessels.
Functions of Blood
Primary function of blood is to deliver oxygen and nutrients to and remove wastes from body cells.
Specific functions also include defense, distribution of heat, and maintenance of homeostasis.
Transportation
Nutrients from digested food travel in the bloodstream to the liver for processing and release to body cells.
Oxygen from inhaled air diffuses into the blood, which moves from the lungs to the heart, then to the rest of the body.
Endocrine glands release hormones into the bloodstream for transport to target cells.
Blood transports cellular wastes (e.g., carbon dioxide) to organs (lungs, kidneys, liver) for removal from the body.
Defense
White blood cells (WBCs) protect the body from external threats (e.g., bacteria) and internal threats (e.g., cancerous cells or virus-infected cells).
Blood platelets and plasma proteins interact to block ruptured blood vessels, preventing further blood loss.
Maintenance of Homeostasis
Blood distributes heat, maintaining body temperature.
Blood proteins act as buffers, regulating the pH of body tissues.
Blood regulates the water content of body cells.
Composition of Blood
Blood tests measure substances within blood and the quantities and types of formed elements.
Hematocrit: A blood test which measures the percentage of red blood cells (RBCs), also known as erythrocytes, in a blood sample.
Blood sample is spun in a centrifuge causing heavier elements to separate from the liquid plasma.
Erythrocytes settle at the bottom of the hematocrit tube.
Buffy coat: A pale, thin layer above the erythrocytes comprises WBCs (leukocytes) and platelets (thrombocytes), which normally constitutes less than 1 percent of blood sample.
Blood plasma, a pale, straw-colored fluid, is located above the buffy coat and constitutes the remainder of the sample.
Packed cell volume (PCV) is the volume of erythrocytes after centrifugation.
Normal blood: About 45 percent of sample is erythrocytes.
Hematocrit can vary by gender and other factors, about 36–50 percent.
Normal hematocrit values for females range from 37 to 47, with a mean value of 41.
Normal hematocrit values for males range from 42 to 52, with a mean of 47.
Mean plasma percentage is the percent of blood that is not erythrocytes:
For females, approximately 59 (100 minus 41).
For males, approximately 53 (100 minus 47).
Characteristics of Blood
Blood color varies with oxygen saturation (bright red when oxygenated, dusky red when deoxygenated).
Blood is viscous, approximately five times greater than water, and sticky.
Viscosity is influenced by plasma proteins and formed elements.
Viscosity impacts blood pressure and flow (more viscous = greater resistance to flow).
Normal blood temperature is slightly higher than body temperature: about (100.4 °F), compared to (98.6 °F).
Blood vessels create friction and resistance, producing heat.
Blood pH averages about 7.4, ranging from 7.35 to 7.45 in a healthy person.
Blood is slightly more basic (alkaline) than pure water (pH 7.0).
Blood contains buffers to regulate pH.
Blood constitutes approximately 8 percent of adult body weight.
Adult males average 5–6 liters of blood.
Females average 4–5 liters.
Blood Plasma
Plasma is about 92 percent water. The other 8 percent consists of dissolved substances, mostly proteins.
Serum is a sample of plasma after clotting factors have been removed.
Plasma Proteins
About 7 percent of the volume of plasma is made of proteins, including plasma proteins, regulatory proteins, enzymes, and some hormones.
Three major groups of plasma proteins:
Albumin: Most abundant plasma protein, manufactured by the liver, serves as a binding protein and transport vehicle for fatty acids and steroid hormones.
Lipids are hydrophobic and binding to albumin enables their transport in the watery plasma.
Albumin is most significant contributor to osmotic pressure of blood and helps to maintain blood volume & blood pressure.
Accounts for approximately 54 percent of the total plasma protein content, in clinical levels of 3.5–5.0 g/dL blood.
Globulins: Second most common plasma proteins. Heterogeneous group with three main subgroups (alpha, beta, and gamma globulins).
Alpha and beta globulins transport iron, lipids, and fat-soluble vitamins A, D, E, and K to the cells; also contribute to osmotic pressure.
Gamma globulins (immunoglobulins) are proteins involved in immunity and are better known as antibodies.
Although other plasma proteins are produced by the liver, immunoglobulins are produced by specialized leukocytes known as plasma cells.
Globulins make up approximately 38 percent of the total plasma protein volume, in clinical levels of 1.0–1.5 g/dL blood.
Fibrinogen: Least abundant plasma protein, produced by the liver, and essential for blood clotting.
Accounts for about 7 percent of the total plasma protein volume, in clinical levels of 0.2–0.45 g/dL blood.
Other Plasma Solutes
Plasma contains electrolytes (sodium, potassium, calcium ions), dissolved gases (oxygen, carbon dioxide, nitrogen), organic nutrients (vitamins, lipids, glucose, amino acids), and metabolic wastes.
All nonprotein solutes combined contribute approximately 1 percent to the total volume of plasma.
Phlebotomy and Medical Lab Technology
Phlebotomists are professionals trained to draw blood.
Venipuncture: Drawing blood from a surface vein in the arm.
Capillary stick: Collection of small quantity of blood from finger, earlobe, or heel of an infant.
Arterial stick: Collection of blood from an artery, used to analyze blood gases.
Blood is analyzed by medical laboratories or used for transfusions, donations, or research.
The American Society of Phlebotomy Technicians issues certificates to individuals passing a national examination.
Medical or clinical laboratories employ a variety of individuals in technical positions:
Medical technologists (MT), also known as clinical laboratory technologists (CLT), typically hold a bachelor’s degree including
perform a wide variety of tests on body fluids, including blood.Medical laboratory technicians (MLT) typically have an associate’s degree but may perform duties similar to those of an MT.
Medical laboratory assistants (MLA) spend the majority of their time processing samples and carrying out routine assignments within the lab.
Production of the Formed Elements
The lifespan of formed elements is brief; most erythrocytes, leukocytes, and platelets live only hours to weeks.
The body must form new blood cells and platelets quickly and continuously.
Donating a unit of blood (approximately 475 mL) requires about 4 to 6 weeks to replace the blood cells, restricting donation frequency.
Hemopoiesis (hematopoiesis): The process by which blood cells are replaced.
Sites of Hemopoiesis
Prior to birth, hemopoiesis occurs in the yolk sac of the developing embryo, the fetal liver, spleen, lymphatic tissue, and red bone marrow.
Following birth, most hemopoiesis occurs in the red marrow, a connective tissue within the spaces of spongy bone tissue.
In children, hemopoiesis can occur in the medullary cavity of long bones.
Extramedullary hemopoiesis: The liver and spleen maintain their ability to generate the formed elements outside the medullary cavity of adult bones.
May be initiated when a disease destroys the bone marrow.
Differentiation of Formed Elements from Stem Cells
All formed elements arise from stem cells of the red bone marrow.
Stem cells undergo mitosis and cytokinesis to give rise to new daughter cells.
Stem cells occupy a hierarchal system, with some loss of the ability to diversify at each step.
Stem Cell Hierarchy:
Totipotent stem cell (zygote): Gives rise to all cells of the human body.
Pluripotent stem cell: Gives rise to multiple types of cells of the body and some of the supporting fetal membranes.
Mesenchymal cell: Develops only into types of connective tissue, including fibrous connective tissue, bone, cartilage, and blood but not epithelium, muscle, and nervous tissue.
Hemopoietic stem cell (hemocytoblast): All of the formed elements of blood originate from this specific type of cell.
Hemopoiesis begins when the hemopoietic stem cell is exposed to hemopoietic growth factors, prompting division and differentiation.
One daughter cell remains a hemopoietic stem cell.
The other daughter cell becomes a more specialized stem cell:
Lymphoid stem cells: Give rise to lymphocytes (T cells, B cells, and natural killer (NK) cells), which function in immunity.
Lymphoid stem cells migrate from the bone marrow to lymphatic tissues (lymph nodes, spleen, and thymus).
B cells mature in the bone marrow, while T cells mature in the thymus.
Myeloid stem cells: Give rise to all other formed elements (erythrocytes, megakaryocytes that produce platelets, and a myeloblast lineage that gives rise to monocytes and granular leukocytes: neutrophils, eosinophils, and basophils).
Hemopoietic Growth Factors
Development from stem cells to precursor cells to mature cells is initiated by hemopoietic growth factors.
Erythropoietin (EPO): A glycoprotein hormone secreted by the interstitial fibroblast cells of the kidneys in response to low oxygen levels, and prompts the production of erythrocytes.
Thrombopoietin: Glycoprotein hormone produced by the liver and kidneys, and triggers the development of megakaryocytes into platelets.
Cytokines: Glycoproteins secreted by a variety of cells (red bone marrow, leukocytes, macrophages, fibroblasts, and endothelial cells) that act locally as autocrine or paracrine factors.
Stimulate the proliferation of progenitor cells and stimulate both nonspecific and specific resistance to disease.
Colony-stimulating factors (CSFs): Glycoproteins that act locally as autocrine or paracrine factors.
Trigger the differentiation of myeloblasts into granular leukocytes such as neutrophils, eosinophils, and basophils.
A different CSF induces the production of monocytes.
GM-CSF stimulates both granulocytes and monocytes.
Multi-CSF stimulates granulocytes, monocytes, platelets, and erythrocytes.
Synthetic forms of these hormones are often administered to patients with various forms of cancer who are receiving chemotherapy to revive their WBC counts.
Interleukins: Cytokine signaling molecules important in hemopoiesis, initially thought to be secreted uniquely by leukocytes to communicate only with other leukocytes, but are now known to be produced by a variety of cells including bone marrow and endothelium.
They may play other roles in body functioning, including differentiation and maturation of cells, and producing immunity and inflammation.
Generally numbered IL-1, IL-2, IL-3, etc.
Blood Doping
Blood doping originally referred to injecting supplemental RBCs into an individual, typically to enhance performance in a sport.
Additional RBCs deliver more oxygen to the tissues, providing extra aerobic capacity (VO2 max).
The source of the cells was from the recipient (autologous) or from a donor with compatible blood (homologous).
These practices are considered illegal in virtually all sports and run the risk of infection, significantly increasing the viscosity of the blood and the potential for transmission of blood-borne pathogens if the blood was collected from another individual.
With the development of synthetic EPO in the 1980s, it became possible to provide additional RBCs by artificially stimulating RBC production in the bone marrow.
Synthetic EPO is injected under the skin and can increase hematocrit for many weeks, and may also induce polycythemia and raise hematocrit to 70 or greater.
This increased viscosity raises the resistance of the blood and forces the heart to pump more powerfully; in extreme cases, it has resulted in death.
Other drugs such as cobalt II chloride have been shown to increase natural EPO gene expression.
Bone Marrow Sampling and Transplants
A bone marrow biopsy is a diagnostic test of a sample of red bone marrow. A bone marrow transplant is a treatment in which a donor’s healthy bone marrow replaces the faulty bone marrow of a patient.
Used to assist in the diagnosis and treatment of various severe forms of anemia (thalassemia major and sickle cell anemia), as well as some types of cancer (leukemia).
Location for procedure: Iliac crest of the pelvic bones.
Now, direct sampling of bone marrow can often be avoided by isolating stem cells in just a few hours from a sample of a patient’s blood.
For an individual requiring a transplant, a matching donor is essential to prevent tissue rejection.
To treat patients with bone marrow transplants, it is first necessary to destroy the patient’s own diseased marrow through radiation and/or chemotherapy.
Donor bone marrow stem cells are then intravenously infused and establish themselves in the recipient’s bone marrow.
Erythrocytes
The erythrocyte, commonly known as a red blood cell (or RBC), is the most common formed element.
Males have about 5.4 million erythrocytes per microliter (µL) of blood, and females have approximately 4.8 million per µL.
Erythrocytes are estimated to make up about 25 percent of the total cells in the body, with a mean diameter of only about 7–8 micrometers (µm).
Primary functions are to pick up inhaled oxygen from the lungs and transport it to the body’s tissues, and to pick up some (about 24 percent) carbon dioxide waste at the tissues and transport it to the lungs for exhalation.
Erythrocytes remain within the vascular network. Movement of erythrocytes from the blood vessels is abnormal.
Shape and Structure of Erythrocytes
As an erythrocyte matures in the red bone marrow, it extrudes its nucleus and most of its other organelles.
During the first day or two that it is in the circulation, an immature erythrocyte, known as a reticulocyte, will still typically contain remnants of organelles.
Reticulocytes should comprise approximately 1–2 percent of the erythrocyte count.
Mature, circulating erythrocytes have few internal cellular structural components.
Lacking mitochondria, they rely on anaerobic respiration.
They also lack endoplasmic reticula and do not synthesize proteins.
Erythrocytes contain some structural proteins (e.g., spectrin) help maintain their unique structure and enable them to change their shape to squeeze through capillaries.
Erythrocytes are biconcave disks; that is, plump at their periphery and very thin in the center.
The biconcave shape gives erythrocytes are greater surface area.
In the capillaries, the oxygen carried by the erythrocytes can diffuse into the plasma and then through the capillary walls to reach the cells, whereas some of the carbon dioxide produced by the cells as a waste product diffuses into the capillaries to be picked up by the erythrocytes.
Capillary beds are extremely narrow, slowing the passage of the erythrocytes, and erythrocytes may have to fold in on themselves if they are to make their way through.
In wider vessels, erythrocytes may stack up much like a roll of coins, forming a rouleaux.
Hemoglobin
Hemoglobin is a large molecule made up of proteins and iron.
It consists of four folded chains of a protein called globin, designated alpha 1 and 2, and beta 1 and 2.
Each of these globin molecules is bound to a red pigment molecule called heme, which contains an ion of iron ().
Each iron ion in the heme can bind to one oxygen molecule.
Each hemoglobin molecule can transport four oxygen molecules.
An individual erythrocyte may contain about 300 million hemoglobin molecules, and therefore can bind to and transport up to 1.2 billion oxygen molecules.
In the lungs, hemoglobin picks up oxygen, which binds to the iron ions, forming oxyhemoglobin.
The bright red, oxygenated hemoglobin travels to the body tissues, where it releases some of the oxygen molecules, becoming darker red deoxyhemoglobin, sometimes referred to as reduced hemoglobin.
About 76 percent of carbon dioxide dissolves in the plasma, some of it remaining as dissolved , and the remainder forming bicarbonate ion. About 23–24 percent of it binds to the amino acids in hemoglobin, forming a molecule known as carbaminohemoglobin.
Ineffective hematopoiesis results in insufficient numbers of RBCs and results in one of several forms of anemia.
An overproduction of RBCs produces a condition called polycythemia.
Ineffective hematopoiesis results in insufficient numbers of RBCs resulting in anemia, while an overproduction of RBCs produces a condition called polycythemia.
In patients with insufficient hemoglobin, the tissues may not receive sufficient oxygen, resulting in another form of anemia.
The value of greatest interest in healthcare is the percent saturation which is the percentage of hemoglobin sites occupied by oxygen in a patient’s blood.
Normal pulse oximeter readings range from 95–100 percent. Lower percentages reflect hypoxemia, or low blood oxygen.
When this method is applied, the amount of oxygen present is expressed in terms of partial pressure of oxygen or simply and is typically recorded in units of millimeters of mercury, mm Hg.
The kidneys filter about 180 liters (~380 pints) of blood in an average adult each day, or about 20 percent of the total resting volume, and thus serve as ideal sites for receptors that determine oxygen saturation.
Interstitial fibroblasts within the kidney secrete EPO, thereby increasing erythrocyte production and restoring oxygen levels.
Populations dwelling at high elevations maintain a hematocrit higher than people living at sea level.
Lifecycle of Erythrocytes
Production of erythrocytes in the marrow occurs at the staggering rate of more than 2 million cells per second.
For this production to occur, a number of raw materials must be present in adequate amounts, including: glucose, lipids, and amino acids, and several trace elements:
Trace Elements:
Iron: Each heme group in a hemoglobin molecule contains an ion of the trace mineral iron. On average, less than 20 percent of the iron we consume is absorbed.
Heme iron, from animal foods such as meat, poultry, and fish, is absorbed more efficiently than non-heme iron from plant foods.
The bone marrow, liver, and spleen can store iron in the protein compounds ferritin and hemosiderin.
Ferroportin transports the iron across the intestinal cell plasma membranes and from its storage sites into tissue fluid where it enters the blood.
When EPO stimulates the production of erythrocytes, iron is released from storage, bound to transferrin, and carried to the red marrow where it attaches to erythrocyte precursors.
Copper: A trace mineral, copper is a component of two plasma proteins, hephaestin and ceruloplasmin. Without these, hemoglobin could not be adequately produced.
Located in intestinal villi, hephaestin enables iron to be absorbed by intestinal cells.
Ceruloplasmin transports copper.
Both enable the oxidation of iron from to , a form in which it can be bound to its transport protein, transferrin, for transport to body cells.
Zinc: Functions as a co-enzyme that facilitates the synthesis of the heme portion of hemoglobin.
B vitamins: Folate and vitamin B12 function as co-enzymes that facilitate DNA synthesis. Thus, both are critical for the synthesis of new cells, including erythrocytes.
Erythrocytes live up to 120 days in the circulation, after which the worn-out cells are removed by a macrophage, located primarily within the bone marrow, liver, and spleen.
Components of Degraded Erythrocytes:
Globin: The protein portion of hemoglobin, is broken down into amino acids, which can be sent back to the bone marrow to be used in the production of new erythrocytes.
Iron: It may be stored in the liver or spleen, primarily in the form of ferritin or hemosiderin, or carried through the bloodstream by transferrin to the red bone marrow for recycling into new erythrocytes.
Non-iron portion of heme: Is degraded into the waste product biliverdin, a green pigment, and then into another waste product, bilirubin, a yellow pigment.
Bilirubin binds to albumin and travels in the blood to the liver, which uses it in the manufacture of bile.
In the large intestine, bacteria breaks the bilirubin apart from the bile and converts it to urobilinogen and then into stercobilin.
Disorders of Erythrocytes
The size, shape, and number of erythrocytes, and the number of hemoglobin molecules can have a major impact on a person’s health.
When the number of RBCs or hemoglobin is deficient, the general condition is called anemia.
Two groupings clinicians often use in diagnosis:
Kinetic Approach: Focuses on evaluating the production, destruction, and removal of RBCs.
Morphological approach: Examines the RBCs themselves, paying particular emphasis to their size. A common test is the mean corpuscle volume (MCV), which measures size.
Normal-sized cells are referred to as normocytic, smaller-than-normal cells are referred to as microcytic, and larger-than normal cells are referred to as macrocytic.
An oxygen deficit in the brain impairs the ability to think clearly, and may prompt headaches and irritability. Lack of oxygen leaves the patient short of breath, even as the heart and lungs work harder in response to the deficit.
Blood loss anemias may be due to ulcers, hemorrhoids, inflammation of the stomach (gastritis), and some cancers of the gastrointestinal tract. The excessive use of aspirin or other nonsteroidal anti-inflammatory drugs such as ibuprofen can trigger ulceration and gastritis. Excessive menstruation and loss of blood during childbirth are also potential causes.
* Anemias caused by faulty or decreased RBC production include sickle cell anemia, iron deficiency anemia, vitamin deficiency anemia, and diseases of the bone marrow and stem cells.
A characteristic change in the shape of erythrocytes is seen in sickle cell disease (also referred to as sickle cell anemia):
A genetic disorder, it is caused by production of an abnormal type of hemoglobin, called hemoglobin S, which delivers less oxygen to tissues and causes erythrocytes to assume a sickle (or crescent) shape, especially at low oxygen concentrations.
These abnormally shaped cells can then become lodged in narrow capillaries because they are unable to fold in on themselves to squeeze through, blocking blood flow to tissues and causing a variety of serious problems from painful joints to delayed growth and even blindness and cerebrovascular accidents (strokes).
Iron deficiency anemia is the most common type and results when the amount of available iron is insufficient to allow production of sufficient heme.
Vitamin-deficient anemias generally involve insufficient vitamin B12 and folate.
*Megaloblastic anemia involves a deficiency of vitamin B12 and/or folate, and often involves diets deficient in these essential nutrients. Lack of meat or a viable alternate source, and overcooking or eating insufficient amounts of vegetables may lead to a lack of folate.
*Pernicious anemia is caused by poor absorption of vitamin B12 and is often seen in patients with Crohn’s disease (a severe intestinal disorder often treated by surgery), surgical removal of the intestines or stomach (common in some weight loss surgeries), intestinal parasites, and AIDS.
Assorted disease processes can also interfere with the production and formation of RBCs and hemoglobin.
Aplastic anemia: The condition in which there are deficient numbers of RBC stem cells. Aplastic anemia is often inherited, or it may be triggered by radiation, medication, chemotherapy, or infection.
Thalassemia: An inherited condition typically occurring in individuals from the Middle East, the Mediterranean, African, and Southeast Asia, in which maturation of the RBCs does not proceed normally. The most severe form is called Cooley’s anemia.
Lead exposure from industrial sources or even dust from paint chips of iron-containing paints or pottery that has not been properly glazed may also lead to destruction of the red marrow.
Various disease processes also can lead to anemias. These include chronic kidney diseases often associated with a decreased production of EPO, hypothyroidism, some forms of cancer, lupus, and rheumatoid arthritis.
Polycythemia is an elevated RBC count that is detected in a patient’s elevated hematocrit. It can occur transiently in a person who is dehydrated; when water intake is inadequate or water losses are excessive, the plasma volume falls. As a result, the hematocrit rises. Polycythemia vera (from the Greek vera = “true”) causes an excessive production of immature erythrocytes. Polycythemia vera can dangerously elevate the viscosity of blood, raising blood pressure and making it more difficult for the heart to pump blood throughout the body. It is a relatively rare disease that occurs more often in men than women, and is more likely to be present in elderly patients those over 60 years of age.
Leukocytes and Platelets
The leukocyte, commonly known as a white blood cell (or WBC), is a major component of the body’s defenses against disease. Leukocytes protect the body against invading microorganisms and body cells with mutated DNA, and they clean up debris. Platelets are essential for the repair of blood vessels when damage to them has occurred; they also provide growth factors for healing and repair.
Characteristics of Leukocytes
Leukocytes: Originate from hematopoietic stem cells in the bone marrow
Far less numerous than erythrocytes: Typically there are only 5000 to 10,000 per µL
Larger than erythrocytes and are the only formed elements that are complete cells, possessing a nucleus and organelles
Many types, with most having a much shorter lifespan than that of erythrocytes a few hours or even a few minutes in the case of acute infection
One of the most distinctive characteristics of leukocytes is their movement: Whereas erythrocytes spend their days circulating within the blood vessels, leukocytes routinely leave the bloodstream to perform their defensive functions in the body’s tissues.
When they arrive, they are often given distinct names, such as macrophage or microglia, depending on their function.
Diapedesis (dia- = “through”; -pedan = “to leap”): Leave the capillaries—the smallest blood vessels—or other small vessels- or Emigration (from the Latin for “removal”) in which they squeeze through adjacent cells in a blood vessel wall.
Positive Chemotaxis: Attracting of leukocytes occurs because of chemical signals in which injured or infected cells and nearby leukocytes emit the equivalent of a chemical “911” call, attracting more leukocytes to the site.
In clinical medicine, the differential counts of the types and percentages of leukocytes present are often key indicators in making a diagnosis and selecting a treatment.
Classification of Leukocytes
Granular leukocytes: Contain abundant granules within the cytoplasm. They include neutrophils, eosinophils, and basophils
While granules are not totally lacking in agranular leukocytes, they are far fewer and less obvious. Agranular leukocytes include monocytes, which mature into macrophages that are phagocytic, and lymphocytes, which arise from the lymphoid stem cell line.
Granular Leukocytes
All of these are produced in the red bone marrow and have a short lifespan of hours to days.
Typically have a lobed nucleus and are classified according to which type of stain best highlights their granules:
Neutrophils: Normally comprise 50–70 percent of total leukocyte count. They are 10–12 µm in diameter, significantly larger than erythrocytes. and are called neutrophils because their granules show up most clearly with stains that are chemically neutral (neither acidic nor basic).
The nucleus has a distinct lobed appearance and may have two to five lobes, the number increasing with the age of the cell. Older neutrophils have increasing numbers of lobes and are often referred to as polymorphonuclear (a nucleus with many forms), or simply "polys."
Neutrophils are rapid responders to the site of infection and are efficient phagocytes with a preference for bacteria.
Abnormally high counts of neutrophils indicate infection and/or inflammation, particularly triggered by bacteria, but are also found in burn patients and others experiencing unusual stress. A burn injury increases the proliferation of neutrophils in order to fight off infection that can result from the destruction of the barrier of the skin
Low counts may be caused by drug toxicity and other disorders and may increase an individual’s susceptibility to infection
Eosinophils: Typically represent 2–4 percent of total leukocyte count. They are also 10–12 µm in diameter. The granules of eosinophils stain best with an acidic stain known as eosin.
The nucleus of the eosinophil will typically have two to three lobes and, if stained properly, the granules will have a distinct red to orange color.
The granules of eosinophils include antihistamine molecules, which counteract the activities of histamines, inflammatory chemicals produced by basophils and mast cells Some eosinophil granules contain molecules toxic to parasitic worms, which can enter the body through the integument, or when an individual consumes raw or undercooked fish or meat.
High counts of eosinophils are typical of patients experiencing allergies, parasitic worm infestations, and some autoimmune diseases Low counts may be due to drug toxicity and stress.
Basophils: The least common leukocytes, typically comprising less than one percent of the total leukocyte count. They are slightly smaller than neutrophils and eosinophils at 8–10 µm in diameter. The granules of basophils stain best with basic (alkaline) stains
Contain large granules that pick up a dark blue stain and are so common they may make it difficult to see the two-lobed nucleus. In general, basophils intensify the inflammatory response. They share this trait with mast cells. In the past, mast cells were considered to be basophils that left the circulation. However, this appears not to be the case, as the two cell types develop from different lineages
The granules of basophils release histamines, which contribute to inflammation, and heparin, which opposes blood clotting.
High counts of basophils are associated with allergies, parasitic infections, and hypothyroidism Low counts are associated with pregnancy, stress, and hyperthyroidism
Agranular Leukocytes: Agranular leukocytes contain smaller, less-visible granules in their cytoplasm than do granular leukocytes. The nucleus is simple in shape, sometimes with an indentation but without distinct lobes. There are two major types of agranulocytes: lymphocytes and monocytes. Lymphocytes are the only formed element of blood that arises from lymphoid stem cells.
Lymphocytes: Account for about 20–30 percent of all leukocytes, and are essential for the immune response.The size range of lymphocytes is quite extensive, with some authorities recognizing two size classes and others three. Typical Lymphocytes includes :Natural killer cells which are capable of recognizing cells that do not express “self” proteins on their plasma membrane: Large Lymphocytes. B cells and T cells, also called B lymphocytes and T lymphocytes, which play prominent roles in defending the body against specific pathogens and are involved in specific immunity Smaller Lymphocytes are B or T cells.
Most smaller lymphocytes are either B or T cells, although its impossible to differentiate in a normal blood smear
Smaller lymphocytes are either B or T cells, although they cannot be differentiated in a normal blood smear High lymphocyte counts are characteristic of viral infections as well as some types of cancer Low lymphocyte counts are characteristic of prolonged (chronic) illness or immunosuppression, including that caused by HIV infection and drug therapies that often involve steroids
Some Smaller lymphocytes are B or T cells, although they cannot be differentiated in a normal blood smear Abnormally high lymphocyte counts are characteristic of viral infections as well as some types of cancer Abnormally low lymphocyte counts are characteristic of prolonged (chronic) illness or immunosuppression, including that caused by HIV infection and drug therapies that often involve steroids
Monocytes: Originate from myeloid stem cells. They normally represent 2–8 percent of the total leukocyte count They are typically easily recognized by their large size of 12–20 µm and indented or horseshoe-shaped nuclei Macrophages are monocytes that have left the circulation that:
Phagocytize debris, foreign pathogens, worn-out erythrocytes, and many other dead, worn out, or damaged cells. Macrophages also release antimicrobial defensins and chemotactic chemicals that attract other leukocytes to the site of an infection. Some macrophages occupy fixed locations, whereas others wander through the tissue fluid Abnormally high counts of monocytes are associated with viral or fungal infections, tuberculosis, and some forms of leukemia and other chronic diseases Abnormally low counts are typically caused by suppression of the bone marrow
Lifecycle of Leukocytes
Most leukocytes have a relatively short lifespan, typically measured in hours or days
Production of all leukocytes begins in the bone marrow under the influence of CSFs and interleukins
Secondary production and maturation of lymphocytes occurs in specific regions of lymphatic tissue known as germinal centers
Lymphocytes are fully capable of mitosis and may produce clones of cells with identical properties. This capacity enables an individual to maintain immunity throughout life to many threats that have been encountered in the past
Disorders of Leukocytes
Leukopenia: A condition in which too few leukocytes are produced. If this condition is pronounced, the individual may be unable to ward off disease
Leukocytosis: Excessive leukocyte proliferation. Although leukocyte counts are high, the cells themselves are often nonfunctional, leaving the individual at increased risk for disease
Leukemia: A cancer involving an abundance of leukocytes. It may involve only one specific type of leukocyte from either the myeloid line (myelocytic leukemia) or the lymphoid line (lymphocytic leukemia) In chronic leukemia, mature leukocytes accumulate and fail to die In acute leukemia, there is an overproduction of young, immature leukocytes In both conditions the cells do not function properly
Lymphoma: A form of cancer in which masses of malignant T and/or B lymphocytes collect in lymph nodes, the spleen, the liver, and other tissues As in leukemia, the malignant leukocytes do not function properly, and the patient is vulnerable to infection Some forms of lymphoma tend to progress slowly and respond well to treatment Others tend to progress quickly and require aggressive treatment, without which they are rapidly fatal
Platelets
You may occasionally see platelets referred to as thrombocytes, but because this name suggests they are a type of cell, it is not accurate A platelet is not a cell but rather a fragment of the cytoplasm of a cell called a megakaryocyte that is surrounded by a plasma membrane
Megakaryocytes are descended from myeloid stem cells and are large, typically 50–100 µm in diameter, and contain an enlarged, lobed nucleus
Thrombopoietin, a glycoprotein secreted by the kidneys and liver, stimulates the proliferation