The Blood
A few nights working in a trauma center would tend to
convince one that the body is just a huge bag of blood. In fact, an
"average" 70 liter human body contains only about 5 liters of blood,
or 7% by volume. In the normal state, blood has no business anywhere except in
the confines of the heart and blood vessels and in the sinusoids of the marrow,
liver, and spleen. Of the average 5 L of blood, only 2.25 L, or 45%, consists
of cells. The rest is plasma, which itself consists of 93% water (by weight)
and 7% solids (mostly proteins, the greatest proportion of which is albumin).
Of the 2.25 L of cells, only 0.037 L (1.6%) are leukocytes. The entire
circulating leukocyte population, if purified, would fit in a bartender's
jigger. The total circulating platelet volume is even less -- about 0.0065 L --
or a little over one teaspoonful.
Erythrocytes
Structurally the simplest cell in the body, volumes
have been written about the lowly red blood cell. The basic function of the rbc
is the creation and maintenance of an environment salutary to the physical
integrity and functionality of hemoglobin. In the normal state, erythrocytes
are produced only in the skeleton (in adults only in the axial skeleton), but
in pathologic states (especially myelofibrosis, which will be covered
subsequently) almost any organ can become the site of erythropoiesis. Numerous
substances are necessary for creation of erythrocytes, including metals (iron,
cobalt, manganese), vitamins (B12, B6, C, E, folate, riboflavin, pantothenic acid, thiamin), and amino
acids. Regulatory substances necessary for normal erythropoiesis include
erythropoietin, thyroid hormones, and androgens. Erythrocytes progress from
blast precursors in the marrow over a period of five days. Then they are
released into the blood as reticulocytes, distinguishable from regular
erythrocytes only with special supravital stains. The reticulocyte changes to
an erythrocyte in one day and circulates for 120 days before being destroyed in
the reticuloendothelial system.
Clinical laboratories measure several important
parameters that reflect rbc structure and function. These measurements are used
to 1) evaluate the adequacy of oxygen delivery to the tissues, at least as is
related to hematologic (as opposed to cardiopulmonary) factors, and 2) detect
abnormalities in rbc size and shape that may provide clues to the diagnosis of
a variety of hematologic conditions. Most of these tests are performed using
automated equipment to analyze a simple venipuncture sample collected in a
universal lavender- (or purple-) top tube containing EDTA as an anticoagulant.
Let us consider each of these tests.
A. Hemoglobin concentration
in whole blood
Referred to simply as
"hemoglobin," this test involves lysing the erythrocytes, thus
producing an evenly distributed solution of hemoglobin in the sample. The
hemoglobin is chemically converted mole-for-mole to the more stable and easily
measured cyanmethemoglobin, which is a colored compound that can be measured
colorimetrically, its concentration being calculated from its amount of light
absorption using Beer's Law. The normal range for hemoglobin is highly age- and
sex-dependent, with men having higher values than women, and adults having
higher values than children (except neonates, which have the highest values of
all). For a typical clinical lab, the young adult female normal range is
12 - 16 g/dL; for adult males it is 14 - 18 g/dL.
This is an easy test to perform, as
hemoglobin is present in the blood in higher concentration than that of any
other measured substance in laboratory medicine. The result is traditionally
expressed as unit mass per volume, specifically grams per deciliter (g/dL).
Ideologues in lab medicine have been maintaining for years that this unit will
be replaced by Système Internationale (SI) units of moles per liter, but this
has not gained any significant acceptance in clinical medicine except in the
most nerdly circles.
B. Erythrocyte count
Also referred to as just "rbc,"
this simply involves counting the number of rbcs per unit volume of whole
blood. Manual methods using the hated hemocytometer have been universally
replaced by automated counting. The major source of error in the rbc count is
an artificially reduced result that occurs in some conditions where rbcs stick
together in the sample tube, with two or more cells being counted as one. The
result of the test is expressed as number of cells per unit volume,
specifically cells/µL. A typical lab's normal range is 4.2 - 5.4 x 106/µL
for females; for adult males it is 4.7 - 6.1 x 106
/µL.
C. Hematocrit
This is also called the packed cell volume
or PCV. It is a measure
of the total volume of
the erythrocytes relative to the total volume of whole blood in a sample. The result is expressed as a
proportion, either unitless (e.g., 0.42) or with volume units (e.g., 0.42 L/L,
or 42 cL/L [centiliters/liter]). An archaic way of expressing hematocrit is
"volumes per cent" or just "percent" (42%, in the above
illustration). Small office labs and stat labs measure hematocrit simply by
spinning down a whole blood sample in a capillary tube and measuring the length
of the column of rbcs relative to the length of the column of the whole
specimen. Larger labs use automated methods that actually measure the volume
individually of each of thousands of red cells in a measured volume of whole
blood and add them up. The volume of individual erythrocytes can be
electronically determined by measurement of their electrical impedance or their
light-scattering properties. The normal range is 0.37 - 0.47 L/L for
females, and 0.42 - 0.52 L/L for males.
D. Erythrocyte indices
The three cardinal rbc measurements
described above (hemoglobin, hematocrit, and rbc count) are used to
arithmetically derive the erythrocyte indices - mean corpuscular
volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin
concentration. As much as we all hate memorization, it is important to know how
to calculate these indices and have some idea of the normal ranges. We will
consider these individually.
1. Mean corpuscular volume
(MCV)
This is the mean volume of all the
erythrocytes counted in the sample. The value is expressed in volume units, in
this case very small ones - femtoliters (fL, 10-15 liter). The normal
range is 80 - 94 fL. The formula for the calculation in general terms
is
MCV = hematocrit ÷ rbc count
When using specific units, decimal
fudge factors are required; for example,
MCV (in fL) = (hematocrit [in
L/L] x 1000) ÷ (rbc count [in millions/µL])
I think that it is easier to forget
the fudge factors, use the first formula, multiply out the values while
ignoring the bothersome decimal, and reposition the decimal in the final result
so as to approximate the order of magnitude of the normal range. This is safe,
since you will not see an MCV of 8 fL, or one of 800 fL.
When the MCV is low, the blood is
said to be (strong>microcytic</STRONGmacrocytic. Normocytic
refers to blood with a normal MCV. Keep in mind that the MCV measures only
average cell volume. The MCV can be normal while the individual red cells of
the population vary wildly in volume from one to the next. Such an abnormal
variation in cell volume is called anisocytosis. Some machines can
measure the degree of anisocytosis by use of a parameter called the red cell
distribution width (RDW). This is simply a standardized parameter (similar
to the standard deviation) for mathematically expressing magnitude of
dispersion of a population about a mean. The normal range for RDW is
11.5 - 14.5 %.
2. Mean corpuscular
hemoglobin (MCH)
The MCH represents the mean mass of
hemoglobin in the RBC and is expressed in the mass unit, picograms (pg, 10-12
gram). The value is determined by the formula,
MCH (in pg) = (hemoglobin [in
g/dL] x 10 ÷ (rbc count [in millions/µL])
Again, a fudge factor is required in
this equation, so it helps to get some feel for the normal range
(27 - 31 pg) and gestalt the decimal point, as described for MCV,
above. Since small cells have less hemoglobin than large cells, variation in
the MCH tends to track along with that of the MCV. The MCH is something of a
minor leaguer among the indices in that it adds little information independent
of the MCV.
3. Mean corpuscular
hemoglobin concentration (MCHC)
This is the mean concentration of
hemoglobin in the red cell. Since whole blood is about one-half cells by
volume, and all of the hemoglobin is confined to the cells, you would correctly
expect the MCHC to be roughly twice the value for hemoglobin in whole blood and
to be expressed in the same units; the normal range is 32 - 36 g/dL.
The value is calculated using the formula,
MCHC [in g/dL] = hemoglobin [in
g/dL] ÷ hematocrit [in L/L]
Cells with normal, high, and low
MCHC are referred to as normochromic, hyperchromic, and hypochromic,
respectively. Again, these terms will have importance in anemia classification.
Iron
Iron
is essential in cells that carry or store oxygen such as red blood cells and
muscle cells. In addition, iron strengthens the immune system, forestalls
fatigue and helps in growth and development. Iron, along with calcium, is one
of the major dietary deficiencies in American women. Because of the blood lost during
menstrual periods, women often benefit from iron supplements. Others that may
benefit include young children, vegetarians, and people who use aspirin.
Deficiency
Red blood cells
Iron
deficiency anemia is a reduction in red blood cell content of the blood. As red
blood cells carry oxygen, anemia results in weakness and fatigue. Iron
deficiency may also be associated with a decreased immune function and impaired
learning ability in children.
Food Sources
Iron
is found in red meat, dried fruit, enriched and whole-grain cereals, peas,
dried beans, asparagus, leafy greens, strawberries, nuts, poultry, and oatmeal.
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