CBC, Peripheral Smear, Reticulocyte count, RBC indices, CRP, ESR, Blood Cell morphology Flashcards
is the process by which the formed elements of blood
are produced
Hematopoiesis
In the bone marrow, the first morphologically recognizable erythroid precursor is the
pronormoblast. This cell can undergo four to five cell divisions, which result in the production of 16–32 mature red
cells.
The mature red cell size
8 μm in diameter, anucleate, discoid in shape, and extremely pliable in order to traverse the microcirculation successfully; its membrane integrity
is maintained by the intracellular generation of ATP.
Normal red cell production results in the daily replacement of 0.8–1% of all circulating red cells in the body, since the average red cell lives 100–120 days. The organ responsible for red cell production is called the erythron.
The erythron is a dynamic organ made up of a rapidly proliferating pool of
marrow erythroid precursor cells and a large mass of mature circulating red blood cells.
The physiologic regulator of red cell production, the glycoprotein hormone
EPO, is produced and released by peritubular capillary lining cells within the kidney
A small amount of EPO is produced by hepatocytes. The fundamental stimulus for EPO production is the availability of O2 for tissue metabolic needs
Key to EPO gene regulation is
hypoxia-inducible factor (HIF)-1α. In the presence of O2, HIF-1α is hydroxylated at a key proline, allowing HIF-1α to be ubiquitinated and degraded via the proteasome
pathway.
EPO level
the normal level being 10–25 U/L. When the hemoglobin concentration falls below
100–120 g/L (10–12 g/dL), plasma EPO levels increase in proportion to the severity of the anemia (Fig. 77-2).
In circulation, EPO has a half-clearance time of 6–9 h. EPO acts by binding to specific receptors
on the surface of marrow erythroid precursors, inducing them to proliferate and to mature
With EPO stimulation, red cell production can increase four- to fivefold within a 1- to 2-week period, but only in the presence of adequate nutrients, especially iron.
mean hematocrit value for adult males and females is
47% (standard deviation, ±7%) and that for
adult females is 42% (±5%).
Any single hematocrit or hemoglobin value carries with it a likelihood of associated anemia.
Thus, a hematocrit of <39% in an adult male or <35% in an adult female has only about a 25% chance of being normal. Hematocrit levels are less useful than hemoglobin levels in assessing anemia because they are calculated rather than measured directly
(WHO) defines anemia as a
hemoglobin level <130 g/L (13 g/dL) in men and <120 g/L (12 g/dL) in women
If blood loss is mild, enhanced O2 delivery is achieved through changes in the O2–hemoglobin dissociation
curve mediated by a decreased pH or increased CO2
(Bohr effect).
With acute blood loss, hypovolemia dominates the clinical picture, and the hematocrit and hemoglobin levels do not reflect the volume of blood lost.
Signs of vascular instability appear with acute losses of 10–15% of the total blood volume.
% of the blood volume is lost suddenly, patients are unable to compensate with the usual mechanisms of vascular contraction and changes in regional blood flow. The patient prefers to remain supine and will
show postural hypotension and tachycardia
> 30
(i.e., >2 L in the average-sized adult), signs of hypovolemic shock including confusion, dyspnea, diaphoresis, hypotension, and tachycardia appear
> 40%
Intravascular hemolysis with release of free hemoglobin may be associated
with acute back pain, free hemoglobin in the plasma and urine, and renal failure.
because of the intrinsic compensatory
mechanisms that govern the O2–hemoglobin dissociation curve, the gradual onset of anemia—particularly in young patients—may not be associated with signs or symptoms until the anemia is
severe
hemoglobin <70–80 g/L [7–8 g/dL]
With chronic anemia, intracellular levels of ___ rise, shifting the dissociation curve to the right and facilitating O2 unloading. This compensatory
mechanism can only maintain normal tissue O2 delivery in the face of a 20–30 g/L (2–3 g/dL) deficit in hemoglobin concentration
2,3-bisphosphoglycerate
Chronic inflammatory states (e.g., infection, rheumatoid arthritis, cancer) areassociated with
mild to moderate anemia
whereas lymphoproliferative
disorders, such as chronic lymphocytic leukemia and certain other B cell neoplasms, may be associated with
autoimmune hemolysis
The skin and mucous membranes may be pale if the
hemoglobin is
<80–100 g/L (8–10 g/dL).
If the palmar creases are lighter in color than the surrounding skin when the hand is hyperextended, the hemoglobin level is usually <80 g/L (8 g/dL).
High-normal hemoglobin values may be
seen in men and women who live at altitude or smoke heavily.
Hemoglobin elevations due to smoking reflect
normal compensation due to the displacement of O2 by CO in hemoglobin binding
TIBC; an indirect measure of
serum transferrin),
Microcytosis is reflected by a lower than normal MCV
(<80), whereas high values (>100) reflect macrocytosis
The MCH and MCHC reflect defects in hemoglobin synthesis (hypochromia)
Mean cell volume (MCV) =
(hematocrit × 10)/(red cell
count × 10^6)
90 ± 8 fL
Mean cell hemoglobin (MCH) =
(hemoglobin × 10)/(red
cell count × 10^6)
30 ± 3 pg
Mean cell hemoglobin concentration =
(hemoglobin × 10)/hematocrit, or MCH/MCV
33 ± 2%
As a complement to the red cell indices, the blood smear also reveals variations in cell size (anisocytosis) and shape (poikilocytosis).
Poikilocytosis suggests a defect
in the maturation of red cell precursors in the bone marrow or
fragmentation of circulating red cells. The blood smear may also
reveal polychromasia—red cells that are slightly larger than normal
and grayish blue in color on the Wright-Giemsa stain. These cells
are reticulocytes that have been prematurely released from the bone
marrow,
In the absence of a functional
spleen, nuclear remnants are not culled from the red cells and remain as small homogeneously staining blue inclusions on Wright stain
Howell-Jolly bodies.
Red cells may become fragmented
in the presence of foreign bodies in the circulation, such as mechanical heart valves, or in the setting of thermal injury
Red cell fragmentation.
Red cell changes in . The left panel
shows a teardrop-shaped cell.
myelofibrosis
The red cells in uremia may acquire numerous
regularly spaced, small, spiny projections. Such cells, called burr cells or echinocytes, are readily distinguishable from irregularly spiculated acanthocytes
Uremia.
Spur cells are recognized as distorted red
cells containing several irregularly distributed thornlike projections.
Cells with this morphologic abnormality are also called
acanthocytes.
This residual RNA is metabolized over the first 24–36 h of the reticulocyte’s life span in circulation. Normally, the reticulocyte count ranges from
1 to 2% and reflects the daily replacement of 0.8–1.0% of the circulating red cell population.
if the EPO and erythroid marrow responses to moderate anemia [hemoglobin <100 g/L (10 g/dL)] are intact, the red cell production rate increases to two to three times normal within
10 days following the onset of anemia
Correction #1 for Anemia:
This correction produces the corrected reticulocyte count.
In a person whose reticulocyte count is 9%, hemoglobin 7.5 g/dL, and hematocrit 23%, the absolute reticulocyte count = 9 × (7.5/15) [or × (23/45)] = 4.5%
Note. This correction is not done if the reticulocyte count is reported in absolute numbers (e.g., 50,000/μL of blood)
Correction #2 for Longer Life of Prematurely Released Reticulocytes in the Blood
This correction produces the reticulocyte production index.
In a person whose reticulocyte count is 9%, hemoglobin 7.5 gm/dL, and hematocrit 23%, the reticulocyte production index
9x
(7.5/15)(hemoglobin correction)/ 2( maturation time concentration)
= 2.25
Erythroid cells take
∼4.5 days to mature.
The normal serum iron ranges
from 9 to 27 μmol/L (50–150 μg/dL), whereas the
normal TIBC is 54–64 μmol/L (300–360 μg/dL); the normal transferrin saturation ranges from 25 to 50%. A diurnal variation in the serum iron leads to a variation in the percent transferrin saturation.
Adult males have serum ferritin levels that average
∼100 μg/L, corresponding to iron stores of ∼1 g.
Adult females have lower serum ferritin levels averaging 30 μg/L, reflecting lower iron stores (∼300 mg). A serum ferritin level of 10–15 μg/L indicates depletion of body iron stores
ferritin is also an acute-phase reactant and, in the presence of acute or chronic inflammation, may rise several-fold above baseline levels.
As a rule, a serum ferritin >
200 μg/L means there is at least some iron in tissue stores
A patient with a hypoproliferative anemia and a
reticulocyte production index <2 will demonstrate an M/E ratio of 2 or 3:1.
In contrast, patients with hemolytic disease and a
Reticulocyte production index >3 will have an M/E ratio of at least 1:1
Erythroid hyperplasia. This marrow shows an
increase in the fraction of cells in the erythroid lineage as might be seen when a normal marrow compensates for acute blood loss or hemolysis. The myeloid/erythroid (M/E) ratio is about 1:1.
Myeloid hyperplasia. This marrow shows an increase
in the fraction of cells in the myeloid or granulocytic lineage as might be seen in a normal marrow responding to infection. The myeloid/ erythroid (M/E) ratio is >3:1