Mcv 5 Nqhctbc41

volume

Example If a patient has a hematocrit of 45 percent red blood cells and if that same person has 5 million red blood cells in each cubic millimeter of blood. Estimate the MCV.

MCV 5-6RBC45 10003 mm3 5 90 3 10"8 m" 5 90 ^

mm3 m3

1 micron 5 1026 meters

A second index measures the amount of hemoglobin in a red blood cell. That index is known as the mean corpuscular hemoglobin index or MCH. MCH may be calculated as shown in Eq. (4.2).

volume

Example If a patient has a hemoglobin concentration of 15 g per 100 mL of whole blood and also has five million red blood cells in each mm3 of blood, then the MCH can be calculated in the following manner:

100 ml 100 ml cm3 103 mm3 12 gm MCH 5 ----- 5-----5 30 x 10-12 - s

5 x 106 RBC/mm3 5 x 106 RBC RBC

A third erythrocyte index is mean corpuscular hemoglobin concentration or MCHC. This index is a measure of the concentration of hemoglobin in whole blood (mass/volume). The MCHC may be calculated as shown below in Eq. (4.3).

Hematocrit

Example For a patient with a hemoglobin concentration of 15 g per 100 mL of whole blood and a hematocrit of 0.45 the MCHC can be calculated as shown below.

15 gm

_ 100 ml _ 0.33 gm of hemoglobin 5 0.45 _ 100 ml blood

4.4.4 Abnormalities of the blood

Anemia is defined as a reduction below normal in the oxygen carrying capacity of blood. This reduction in oxygen carrying capacity could be a result of a decrease in the number of red blood cells in the blood, or it could be a result in a decrease in hemoglobin in each red blood cell, or it could be caused by both.

A macrocytic hyperchromic anemia is an anemia in which a greatly reduced number of red blood cells are too large (macrocytic), have too much hemoglobin and are therefore too red (hyperchromic). These large, red erythrocytes lack erythrocyte maturation factor. This lack can sometime be related to a vitamin B12 deficiency.

Polycythemia is defined as an increase in the number of erythrocytes per cubic millimeter of whole blood above 6 million. Relative polycythemia can be a result of increased concentration of red blood cells due to decreased blood volume, for example as a result of dehydration. Polycythemia vera, however, results from hyperactivity of the bone marrow. It is sometimes difficult to determine the cause of polycythemia vera, but it may be symptomatic of tumors in the bone marrow, kidney, or brain.

4.5 Leukocytes

Leukocytes are also known as white blood cells. Leukocytes can be broadly defined into two groups, arranged by function—phagocytes and immuno-cytes. They could also be arranged into two groups by appearance— granulocytes and agranulocytes. Healthy whole blood normally contains approximately 4000 to 11,000 leukocytes in each cubic millimeter. If you compare that number to 5 million erythrocytes per cubic millimeter, then one would expect to see around 500 erythrocytes for every leukocyte.

TABLE 4.1 Various Types of Leukocytes Grouped in Order of Their Relative Numbers

Name

Count per mm3

Size, ^

Neutrophil

2500-7500

10-15

Lymphocyte

1000-3000

10-20

Monocyte

200-800

20-25

Eosinophil

40-400

10-15

Basophil

10-100

10-12

Total leukocytes

4000-11000

Leukocytes are translucent. If we look at an unstained blood smear under the microscope normally, we will not see any leukocytes. If we searched very carefully and diligently, perhaps we could find what appears as a white blood cell ghost. Leukocytes each contain a nucleus and other organelles and are easy to find after staining.

The two groups of leukocytes based on function are the phagocytes, which spend their time eating foreign bodies, and immunocytes, which are involved in the body's immune response. Phagocytes include neu-trophils, eosinophils, monocytes, and basophils. The cells known as immunocytes are lymphocytes (see Table 4.1).

If we divide white blood cells into groups based on appearance, rather than function, the two groups are granulocytes and agranulocytes. The granulocytes are more granular in appearance compared to the agran-ulocytes. Granulocytes include neutrophils, eosinophils, and basophils. The agranulocytes include monocytes and lymphocytes. Monocytes are the only phagocytes that are not granulocytes.

4.5.1 Neutrophils

Neutrophils are the most abundant type of leukocyte and are granulocytes. Neutrophils have a characteristic appearance with a two to five lobed nucleus. Figure 4.4 shows a photograph of a neutrophil. The lifespan of neutrophils is around 10 h. Neutrophils are motile and phagocytic and they play a key role in the body's defense against bacterial invasion. They are the first leukocytes to arrive at an area of tissue damage.

Neutrophil leukocytosis is an increase in the number of circulating neutrophils to a level greater than 7500 per mm3. Neutrophil leukocytosis is the most frequently observed change in the blood count. A few causes of this include inflammation and tissue necrosis, for example, as a result of a myocardial infarction, acute hemorrhage, and bacterial infection. Acute infections such as appendicitis, smallpox, or rheumatic fever can result in leukocytosis. If the neutrophil count becomes considerably less than normal, it can also be due to a viral infection like influenza, hepatitis, or rubella.

Figure 4.4 A photomicrograph of a neutrophil. Note the four lobed nucleus.

Physiologic leukocytosis occurs in newborn infants, pregnancy and after strenuous exercise, when the number of circulating neutrophils can increase about 7500 per mm3 with no associated pathology.

4.5.2 Lymphocytes

Lymphocytes are the immunological component of our defense against foreign invasion of the body. The lymphocytes make up about a fourth of the circulating leukocytes. Lymphocytes are nonphagocytic and a primary function of these cells is the release of antibody molecule and antigen disposal.

B lymphocytes originate in the bone marrow and make up about 20 percent of lymphocytes. These cells synthesize antibody molecules. The type of immunity that involves B lymphocytes is known as humoral immunity. The B cells fight against bacteria.

T lymphocytes on the other hand originate in the thymus gland and make up about 80 percent of lymphocytes. These T cells are preconditioned to attack antigens either directly or by releasing chemicals to attract neutrophils and B lymphocytes. T lymphocytes do not produce antibodies directly. On the other hand, T cells multiply and clone more T cells which are also responsive to some antigen. This is known as cell mediated immunity. T cells fight against bacteria, viruses, protozoa, and fungi. T cells also fight against things like transplanted organs. Patients with acquired immune deficiency syndrome (AIDS) monitor their T-cell levels; an indicator of the AIDS virus' activity. Figure 4.5 shows a photomicrograph of a lymphocyte.

Figure 4.4 A photomicrograph of a neutrophil. Note the four lobed nucleus.

Figure 4.5 A photomicrograph of blood showing a lymphocyte.

Lymphocytosis is defined as an increase in the number of circulating lymphocytes above normal. There are normally 1000 to 3000 lymphocytes in a cubic millimeter of blood. When the number of circulating lymphocytes becomes 10,000 per mm3 for example, this is known as lymphocytosis. Some causes of acute lymphocytosis include infectious mononucleosis, rubella, mumps, and HIV. Some causes of chronic lym-phocytosis might include tuberculosis or syphilis.

The life span of a lymphocyte is weeks to months. A large number of inherited or acquired deficiencies in any of the components of the immune system may cause an impaired immune system response. Apri-mary lack of T lymphocytes, as in AIDS, leads not only to bacterial infections, but also to viral, protozoal, and fungal infections.

4.5.3 Monocytes

Monocytes are mobile and actively phagocytic and are larger than other leukocytes. They have a large central oval or indented nucleus. They circulate in the blood stream for 20 to 40 h and then leave the blood stream to enter the body's tissues and mature and differentiate into macrophages. Macrophages carry out a function similar to that of a neutrophil. Macrophages may live for several months or even years!

Three to nine percent of all circulation leukocytes are monocytes. They increase in number in patients with malaria, mononucleosis, typhoid fever, and Rocky Mountain spotted fever.

4.5.4 Eosinophils

Eosinophils are granulocytes and they have a special role in allergic response or defense against parasites and in the removal of fibrin formed during inflammation. The primary function of eosinophils is detoxification of foreign proteins. The number of eosinophils in whole blood is

Figure 4.5 A photomicrograph of blood showing a lymphocyte.

normally zero to three percent of leukocytes. However, in allergic reactions this percentage increases. Eosinophils increase in numbers due to bronchitis, bronchial asthma, or hay fever.

4.5.5 Basophils

Basophils are only occasionally seen in normal peripheral blood. One function of a basophil is to release histamine in an area of tissue damage in order to increase blood flow and to attract other leukocytes to the area of damage. Basophils increase in number in response to hemolytic anemia or chicken pox.

4.5.6 Leukemia

Leukemia is a group of disorders characterized by the accumulation of abnormal white cells in the bone marrow. Another way to say this is that there is a purposeless malignant proliferation of leukopoietic tissue. Leukopoietic tissue is the tissue, which forms leukocytes. This type of leukopoietic tissue is found in bone marrow, lymph nodes, spleen, and thymus for example. Some common features of leukemia include a raised total white cell count, abnormal white blood cells in peripheral blood, and evidence of bone marrow failure.

4.5.7 Thrombocytes

Thrombocytes are also known as platelets. Platelets come from megakaryocytes which are giant (30 |im) cells from bone marrow. The mean diameter of a platelet is about 1 to 2 |im or about 1/4 to 1/8 the diameter of an erythrocyte.

The normal lifespan of thrombocytes is seven to ten days. The normal platelet count in healthy humans is about 250,000 platelets per cubic millimeter of whole blood. Young platelets spend up to 36 h in the spleen after being released from the bone marrow.

Platelets are granular in appearance and have mitochondria but no nucleus. The main function of platelets is the formation of mechanical plugs during normal hemostatic response to vascular injury. Platelet reactions of adhesion, secretion, aggregation, and fusion are important to this hemostatic function. Thrombocytes are shown in Fig. 4.6 and are marked with a "t."

4.6 Blood Types

ABO blood types are genetically inherited. To understand blood types, we must first learn a few vocabulary words related to the immune system and genetics. Antibodies, or immunoglobulins, are a structurally related

Figure 4.6 Shows a photomicrograph of blood showing thrombocytes, marked "t."

class of glycoprotein, which are produced in response to a specific antigen. Antigens on the other hand, are any substance, which attracts antibodies. This could include foreign proteins, toxins, bacteria, and virus.

An allele is any alternative form of a gene that can occupy a particular chromosomal locus. A genotype is the genetic makeup of an individual; or the alleles present at one or more specific loci. A phenotype is the entire physical, biochemical, and physiological makeup of an individual (as opposed to genotype).

The three alleles associate with the ABO blood groups are IA, IB, and i. Alleles IA and IB are dominant to i, but show no dominance with respect to one another. Each person has two alleles, one inherited from each parent. For example, if a person inherits the IA allele from each parent, he or she will have the IA/IA genotype and blood type A (phenotype).

Agglutination is the term for the aggregation of erythrocytes into clumps. Severe agglutination can lead to death. Agglutinogens (or antigens) are substances on the membranes of erythrocytes. Agglutinins are antibodies in the plasma, which try to attack specific agglutino-gens. This is known as an antibody-antigen reaction.

Persons with type A blood have the IA/IA genotype and their erythrocytes have the A antigen (agglutinogen) and the 3 or anti-B antibody (agglutinin). If this person received a transfusion of type B blood, his/her antibodies would attack the antigens on the donor erythrocytes and cause agglutination.

Persons with type B blood have the B antigen. Persons with type AB blood have both the A and the B antigens on their erythrocytes. Finally, people with type O blood have no A or B antigens on their erythrocytes.

Table 4.2 shows phenotypes and genotypes of the four blood groups along with their respective antigens and antibodies. Note that persons with A blood have the 3 antibody, persons with type B blood have the a

TABLE 4.2 Blood Types, Distributions and Their Associate Antigens and Antibodies

Population

distribution

Blood type

Blood group

Erythrocyte antigen

Plasma antibody

whites, lowa

phenotype

genotype

(agglutinogens)

(agglutinins)

(for example)

A

IA/IAor IA/i

A

Anti-B (b)

42%

B

IB/IB or IB/i

B

Anti-A (a)

9%

AB

IA/IB

A and B

Neither

4%

O

i/i

Neither

Anti-A and

antibody and persons with O blood have both the a and b antibodies. Figure 4.7 shows the relative population distributions of the various blood types among white North Americans.

Persons with AB blood have no antibodies and are therefore known as universal recipients. Persons with type O blood have both antibodies but no A or B antigens on their red blood cells and are therefore known as universal donors.

H is a weak antigen and nearly all people have it. The IA and IB alle-les cause H to be converted to the A or B antigen. On the other hand, people with type O have more H antigen since it is not converted.

4.6.1 Rh blood groups

Rh antigen was named for the rhesus monkey in which it was first detected. Today over 40 Rh antigens are known in humans. One of these antigens is a strong antigen and can lead to transfusion problems.

A person who is Rh negative does not have the Rh antigen and normally does not have the antibody. Upon exposure to the Rh antigen, Rh negative persons develop the antibody. An Rh— mother can produce antibodies after the birth of an Rh+ neonate after mixing of the mother's

Figure 4.7 Shows the population distribution of ABO blood types among white Iowans.

blood and the newborn's blood occurs. If that Rh—ve mother with antibodies has a second pregnancy and the fetus is Rh+ve, the antibodies will cross over the placenta and begin to destroy fetal erythrocytes (ery-throblastosis fetalis). Some of these babies can be saved by transfusion.

Tests can now reveal the presence of the fetal Rh+ve cells in the blood stream of the Rh—ve mother. When such cells are present, the expectant mother is given injections of the antibody. Because the antibody reacts with and covers up the antigen, the mother's immune system is not stimulated to produce its own antibodies.

4.6.2 M and N blood group system

Many other antigens exist and although they may not be medically important in transfusions, they can be used to study genetics and are used in tests involving disputed parenthood.

Two antigens, M and N exist and the alleles for production of these antigens show no dominance to each other. There are therefore three corresponding genotypes: M, MN, and N. The M phenotype is the blood type with the M antigen located on the erythrocyte and is associated with the M/M genotype. Table 4.3 shows a list of MN phenotypes along with their respective genotypes and antigens.

4.7 Plasma

Plasma is a transparent amber fluid and is 90 percent water by volume. The 10 percent that is not water on the other hand adds some very important characteristics to the function of blood.

Plasma contains inorganic substances like sodium ions, potassium ions, chloride ions, bicarbonate ions, calcium ions and those chemicals make up about 1 percent of the plasma by volume. Plasma proteins make up about 7 percent of plasma by volume. Those proteins include albumins, globulins, and fibrinogens. In plasma there is a further ~1 percent by volume of nonprotein organics and also varying amounts of hormones, enzymes, vitamins, and dissolved gases.

Plasma proteins are large molecules with high molecular weight that do not pass through the capillary wall. They remain in the blood vessel and establish an osmotic gradient.

TABLE 4.3 MN Phenotypes and Their Associated Genotypes and Antigens

Phenotype

Genotype

Erythrocyte antigen

M

M/M

M

MN

M/N

M and N

N

N/N

N

Albumin accounts for most of the plasma protein osmotic pressure. Human plasma contains about 4 to 5 g of albumin per 100 mL of plasma. Albumin is important in binding certain substances that are transported in plasma, such as barbiturates and bilirubin.

Globulins are present in human plasma at the rate of approximately 2 to 3 g per 100 mL plasma. The normal albumin/globulin ratio is approximately two. Fibrinogen is a plasma protein that is involved in hemo-stasis. Hemostasis is the process by which loss of blood from the vascular system is reduced (blood clotting).

4.7.1 Plasma viscosity

Plasma viscosity is a function of the concentration of plasma proteins of large molecular size. This is particularly true of the proteins with pronounced axial asymmetry. Fibrinogen and some of the immunoglobulins fall in this category. Normal values of viscosity at room temperature are in the range of 1.5 to 1.7 cP (1.5 to 1.7 X 10~3 Ns/m2).

4.7.2 Electrolyte composition of plasma

One equivalent (eq) contains Avogadro's number of positive or negative charges (6 X 1023 charges).

Therefore, for singly charged (univalent ions) one equivalent of ions is equal to 1 mole and therefore 1 meq = 1 mmol.

Table 4.4 shows the electrolyte composition of plasma. Note that sodium is an important ion in plasma, which contains 142 meq/L. This is the same as 142 mmol/L. Plasma also contains 5 meq/L of calcium ion, which is the same as 2.5 mmol per liter because calcium is a doubly charged ion.

Osmotic pressure is defined as the pressure that builds up as a result of the tendency of water to diffuse down the concentration gradient. On the other hand, oncotic pressure is osmotic pressure due to plasma proteins.

Osmolarity, in units of Osm/L, is the measure of the concentration of a solute, which would cause an osmotic pressure. Osmolarity is equal to molar concentration multiplied by the number of ionized particles in

TABLE 4.4 Electrolyte Composition of Plasma

Substance

Symbol

meq/L

Substance

Symbol

meq/L

Sodium

Na+

142

Chlorine

Cl~

103

Potassium

K+

4

Bicarbonate

HCO3

28

Calcium

Ca++

5

Proteins

17

Magnesium

Mg+

2

Others

5

Total

153

153

the solution. When a solute has the concentration of 1 Osmole (Osm) it would have an osmotic pressure of 22.4 atm compared to pure water. Human plasma has the same osmotic pressure as 0.9 percent NaCl solution (physiologic or isotonic saline).

0.9 percent NaCl is a solution that has 9 g of NaCl in 1000 g of water or 9 g of NaCl per liter of water. One mole of NaCl contains 23 g of solium and 35 g of chlorine for a total of 58 g of sodium chloride. The molar concentration of isotonic saline is 9 g of sodium chloride in 1 L of water or 9/58 = 155 mmolar. The osmolarity of isotonic saline is 155 mmolar multiplied by 2 ionized particles (sodium and chloride) or 310 mOsm.

When erythrocytes are placed in an isotonic solution, they do not change size. When they are placed in a hypertonic solution, water passes out of the cell and they shrink. When the erythrocytes are placed in a hypotonic solution (0.35 percent NaCl for example) they swell to a nearly spherical shape and in some cases undergo hemolysis.

4.8 Blood pH

The pH or normal healthy blood is in the range of 7.35 to 7.45. When the pH is less than 7.35 this condition is defined as acidosis. When the pH is greater than 7.45, this condition is defined as alkalosis. CO2 dissolved in water in plasma produces carbonic acid, which lowers blood pH. Bicarbonate and carbonic acid form an acid-base buffer pair, which help to keep the arterial pH near 7.4. When PCO2 decreases, then the pH increases.

The ratio of bicarbonate concentration to partial pressure of CO2 in blood is a ratio of metabolic compensation to respiratory compensation. The Henderson Hasselback equation can be used to calculate the pH of arterial blood based on that ratio.

Where the bicarbonate concentration is given in milliequivalents per liter and the partial pressure of carbon dioxide is given in millimeters of mercury. The normal ratio of metabolic compensation to respiratory compensation can be estimated as follows:

4.9 Clinical Features

An imbalance of acid generation or removal due to either lungs or kidneys is usually compensated by a nearly equal and opposite change in the other organ. For example, diarrhea with a loss of bicarbonate-containing fluids will trigger hyperventilation and respiratory compensation to eliminate enough CO2 to compensate for the bicarbonate loss in the stool. Conversely, vomiting with loss of stomach hydrochloric acid results in metabolic alkalosis for which hypoventilation and an increase in blood CO2 is the compensation.

Bibliography

Hoffbrand AV, Pettit JE., Essential Haematology. 3rd ed. Blackwell Science; 1998. Selkurt EE. Basic Physiology for the Health Sciences. Boston, Little, Brown & Co; 1982.

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