CHAPTER 59 ANEMIA AND POLYCYTHEMIA Flashcards
Process by which the formed elements of blood are produced
hematopoiesis
what is the primary regulatory hormone for red cell production
epo (erythropoietin)
where can you find the first morphologically recognizable erythroid precursors?
bone marrow
what do you call the first morphological recognizable erythroid precursor
pronormoblast
characteristic of mature red blood cell
8 um in diameter
anucleate
discoid in shape
extremely pliable
average life span of red blood cell
100-120 days
what do you call the organ responsible for red cell production
erythron
most important factor that will affect the production of EPO
0xygen levels in body for tissue metabolic needs
where in kidney, the epo is produced?
peritubular capillary lining of kidney
do hepatocytes produce small amount of EPO?
true
what is the key to EPO gene regulation
hypoxia inducible factor
what do you call decreased red cell mass
anemia
what do you call the impaired oxygen loading of the hemoglobin
hypoxemia
what do you call the disease caused by impaired blood flow of the kidney
renal artery stenosis
what level of hemoglobin concentration that will trigger the increase of EPO levels
below 100-120 g/L
mechanism of action of EPO
it will bind to the specific receptors in the surface of marrow erythroid precursors inducing them to proliferate and to mature
effect of EPO to the red cell production
increase to four to five fold within 1-2 week period but only in the presence of adequate nutrients especially iron
laboratory result in anemia
hemoglobin level <130 g/L in men and <120 g/L for women
what are the critical elements of erythropoiesis
EPO production
iron availability
the proliferative capacity of the bone marrow
effective maturation of red cell precursors
cause of acute anemia
blood loss or hemolysis
if blood loss is mild what will happened to the curve
if blood loss is mid, enhanced O2 delivery is achieved thru changes in the 02 hemoglobin dissociation curved mediated by decreased ph or increased co2 (bohr effect)
when will the signs of vascular instability shows?
when there is acute losses of 10 to 15% of total blood volume
what will happen if there is >30% of blood volume loss
px unable to compensate and there will be changes in vascular flow and the px will prefer to remain supine and will show postural hypotension and tachycardia
if the blood is >40% what will happen to the px
the px will show signs of hypovolemic shock including confusion, dyspnea, diaphoresis, hypotension and tachycardia
how do you evaluate px with anemia
careful history and physical examination
nutritional history related to drugs and alcohol intake and family history of anemia should be assessed
what symptoms you should look for?
signs of bleeding fatigue malaise fever weight loss night sweats
what do splenomegaly and lymphadenopathy suggest?
underlying lymphoproliferative disease
in anemic px, physical examination will demonstrate a
forceful heartbeat
strong peripheral pulses
systolic flow murmur
where should you focus your physical examination?
focus on areas where vessels are close to the surface such as the mucous membrane, nail beds, palmar creases
when the palmar creases are lighter in color than the surrounding skin when the hand is hyperextended, what is usually the hemoglobin level
<80 g/L
physiologic factors that may affect the CBC
age sex pregnancy smoking altitude
when can you say that it is microcytosis
lower MCV <80
When can you say it is macrocytosis
> 100 MCV
what can you get in peripheral blood smear
reveals the variations of cell size (anisocytosis) and shape (poikilocytosis)
what poikilocytosis suggests?
defect in the maturation of red cell precursors in the bone marrow
what is polychromasia
red cell that are slightly larger than normal and grayish-blue in color on the
what do you call those red cell that may appear larger and grayish in color??
reticulocytes
the color of reticulocytes represents the
residual amount of ribosomal rna
what is the key to initial classification of anemia
accurate reticulocyte count
how is reticulocytes identified?
by staining with supravital dye that precipitates the ribosomal RNA
The result of supravital dye
appear as blue or blank punctuate spots and can be counted manually or by fluorescent emission of dyes that bind RNA
To use the reticulocyte count, there is two correction necessary what are those?
first: adjust the reticulocyte count based on the reduced number of circulating cells
second: peripheral blood smear is examined to see if there are polychromatophilic macrocytes present
why there is a need to correct?
because they are called shift cells and they survive as reticulocytes in circulation for >1 day thereby providing a falsely high estimate of daily red cell production
what do you call the doubly corrected reticulocyte?
reticulocyte production index
what laboratory measurements reflect the availability of the iron for hemoglobin synthesis?
serum iron
TIBC
percent transferrin saturation
how to get the percent transferrin saturation?
dividing the serum iron level by the TIBC
What is the normal serum iron range?
9 to 27 umol
what is normal TIBC?
54 to 64 umol/L
normal transferrin saturation
25 to 50%
what is used to evaluate total body iron stores?
serum ferritin
adult males have serum ferritin levels has average of ?
100ug/L
adult females have serum ferritin levels at?
30 ug
what serum ferritin level considered as depletion of body iron stores
10-15 ug
how to check if there is an increase or decrease of one cell lineage?
differential count of nucleated cells in bone marrow smear
what will be the ratio of px with hypoproliferative anemia and the reticulocyte production index?
M/E ratio of 2:3:1
reticulocyte index of <2
what will be the ratio of px with hemolytic disease and reticulocyte production index?
ratio of 1:1
reticulocyte production index of <2
what is the form of storage iron?
form of ferritin or hemosiderin
what do you call small ferritin granules that can be seen under oil immersion in developing eryhthroblast?
sideroblast
what are the three categories of functional anemia
marrow production defects (hypoproliferation)
red cell maturation defects (ineffective erythropoiesis)
decreased red cell survival (blood loss or hemolysis)
what is the reticulocyte production index of hypoproliferative anemia and its cell morphology?
low reticulocyte index with normocytic, normochromic anemia
what is the reticulocyte production index of maturation disorders and the cell morphology?
slight to moderate elevated reticulocyte production index accompanied with macrocytic or microcytic
what the branch of anemia where the reticulocyte production index is >2.5
hemolysis
examples of hemolysis or hemorrhage?
blood loss intravascular hemolysis metabolic defect membrane abnormality hemoglobinopathy immune destructions fragmentation hemolysis
what branch of anemia where the reticulocyte production indes is <2.5
red cell morphology such as hypoproliferative and maturation disorder
what is the cell morphology in px with hypoproliferative anemia
normocytic normochromic
what cell morphology is seen in px with maturation disorder?
micro or macrocytic
examples of hypoproliferative?
marrow damage iron deficiency inflammation metabolic disease renal disease
examples of maturation disorder
cytoplasmic defects
nuclear defects
most cases of anemia are
hypoproliferative anemia
hypoproliferative anemia reflects?
absolute or relative marrow failure in which degree of erythroid marrow has not proliferated appropriately
causes of hypoproliferative anemia?
marrow damage iron deficiency inadequate EPO stimulation impaired renal function inflammation
what are the key laboratory test in distinguishing between various form of anemia
serum iron iron binding capacity evaluation of renal and thyroid function marrow biopsy aspirate to detect marrow damage or infiltrate disease serum ferritin
what is used to determine the pattern of iron distribution?
iron stain
what is the pattern for px with anemia of acute or chronic inflammation
serum iron low
TIBC normal or low
percent transferrin saturation low
serum ferritin high or normal
what is the iron regulatory hormone that is released in the liver?
hepcidin
what is the pattern in mild iron deficiency anemia
low serum iron
high TIBC
low percent transferrin saturation
low serum ferritin
how to diagnose marrow damage by drugs and infiltrative disease such as leukemia or lymphoma
peripheral blood and bone marrow morphology
the presence of anemia with an inappropriate low reticulocyte production index, macro-microcytes on smear and abnormal red indices suggest?
maturation disorder
what is the cause of inappropriately low reticulocyte production index?
ineffective erythropoiesis that results from the destruction within the marrow of developing erythroblasts
causes of nuclear maturation defects?
vitamin b12 or folic acid deficiency
drug damage or myelodysplasia
drugs that can cause damage DNA synthesis
alcohol
examples of drugs that interfere with DNA synthesis
methotrexate or alkylating agents
causes of cytoplasmic maturation defects?
severe iron deficiency
abnormalities in globin or heme synthesis
acute blood loss is not associated with an increased reticulocyte production index because of the time required to increase EPO production and subsequently marrow proliferation
true
what is the most important step before initiating treatment for anemia?
evalutate the px iron stores status before and during the treatment of any anemia
what is the most important step before initiating treatment for anemia?
evalutate the px iron stores status before and during the treatment of any anemia
what is the treatment for px with anemia with chronic renal failure and in dialysis
recombinant EPO
What is the treatment for px with inherited genetic conditions?
targeted genetic therapy
it is defined as increased in the hemoglobin above normal
polycythemia
the difference between erythrocytosis and polycythemia
erythrocytosis-documentation increased red cell mass
polycythemia-any increase in red cell
hematocrit level considered as abnormal
> 50 percent for men
>45 for women
features of clinical history that are useful for differentials?
smoking history current living at high altitude history of diuretic use congenital heart disease sleep apnea chronic lung disease
classic symptoms in polycythemia
hyperviscosity and thrombosis both venous and arterial
neurologic symptoms
symptoms of polycythemia vera
aquagenic pruritus hepatosplenomegaly easy bruising epistaxis peptic ulcer
p.e in px with polycythemia vera
ruddy complexion
the presence of cyanosis or evidence of left to right shunt suggest?
congenital heart disease such as tetralogy of fallot or Eisenmenger syndrome
increased blood viscosity can raise pulmonary artery pressure while hypoxemia can lead to increased pulmonary vascular resistance can lead to?
cor pulmonale
how to document polycythemia using the principle of isotope dilution
use Cr-labeled autologous red blood cells to the px and sampling blood radioactivity for 2 hours
if the result of dilution normal, the px has?
spurious or relative polycythemia
if the result of the dilution is high red cell mass, what should be done?
measure epo and if the epo is low then the px has polycythemia vera
and if the EPO is elevated?
distinguish whether elevation is a physiologic response to hypoxia or related to autonomous EPO production
why is it that smokers has normal o2 saturation but have elevated EPO levels
because of CO displacement ofO2
if the carboxyhemoglobin levels are high what should be the diagnosis?
smoker’s polycythemia
what is the treatment for smoker’s polycythemia
stop smoking
if not then they require phlebotomy to control their polycythemia
