09. Blood count , Class. of Anemia , Iron Metabolsim ,Microcytic Hypochromic Anemia Flashcards
Blood count
brings information about
platelets,
leukocytes,
erythrocytes (RBC).
PLATELETS
normal values: 150,000 – 450,000/mmc
WHITE BLOOD CELLS
normal values: 4,000 - 10,000/mmc
Leukocyte formula:
Neutrophils 30-60%
Lymphocytes 20-50%
Monocytes 2-10%
Eosinophils 0-5%
Basophils 0-1%
TYPE OF LEUKOCYTES
INCREASED
POSSIBLE CAUSES - look at the lp
LEUCOPENIA
< 4,000/MMC
TYPE OF LEUKOCYTE
DECREASED
POSSIBLE CAUSES - look at the lp
ERYTHROCYTES (RED BLOOD CELLS)
Basic Parameters:
- Hemoglobin
- Red blood cells count
- Hematocrit
Erythrocyte Indices:
MCV
MCH
MCHC
HEMOGLOBIN (HB)
Detection: transformation of all forms of Hb (oxy,
carboxy) in cianmetHb and then, a spectrophotometric
determination is performed.
Normal values in pregnant women and children 6
months-6 years: Hb = 11-14 g / dl
Normal values in women: Hb = 12-15 g / dl
Normal values in men: Hb = 13-16 g / dl
ANEMIC SYNDROME
= Decreased value of Hb below the normal inferior
limit for age, sex and physiological status.
always requires further investigation.
Depending on Hb value it is considered:
1) Mild anemic syndrome > 9 g/dl resting tachycardia
2) Moderate anemic syndrome 7-9 g / dl resting tachycardia + pallor
3)Severe anemic syndrome 7 g / dl resting tachycardia + pallor + polypnea
RED BLOOD CELLS COUNT
the number is expressed in millions / mmc.
automatic counters use counting rooms which measure the light
scattering or impedance.
normal values in women: 4.5 million / mmc
normal values in men: 5 mil / mmc
HEMATOCRIT (HT)
- is the proportion of blood volume occupied by RBCs
- Ht = (erythrocyte volume x 100 ) / total blood volume
- blood is collected on heparin anticoagulant + then centrifugated
- from top to bottom we will find plasma , leukocytes + platelets + erythrocytes
Normal values :
women Ht = 40 +/- 2 %
men Ht = 45 +/- 2% ;
MCV ( Mean Corpuscular Volume )
MCV = ( Ht x 10 ) / RBC count expressed in femtoliters ( 1fl = 10 in -5 liter )
Normocytosis = 80 - 100 fl
Microcytosis = MCV < 80 fl
Macrocytosis =MCV > 100 fl
MCH (MEAN CORPUSCULAR HEMOGLOBIN)
MCH = ( Hb x 10 ) / RBC count expressed in picograms ( 10 in -12 grams )
MCH normal = 27 - 32 pg of little importance in evaluating RBC - depends on the volume of RBC
MCHC (MEAN CORPUSCULAR HEMOGLOBIN
CONCENTRATION)
- Represents the average cncentration of Hb found in erythrocyte volume
- MCHC = ( Hb /Ht ) x 100 expressed in g / dl of RBCs ( not blood )
Normochromia - MCHC = 32 -36 g /dl
Hypochromia - MCHC < 32 g / dl
RETICULOCYTES
- are immature red blood cells with 24 h lifespan,
- typically composing 0.5-1.5% of the red cells when the hemoglobin levels are normal.
- anemia with normal or low reticulocyte percentage indicates decreased production of reticulocytes (the bone marrow is not functional and it’s the cause of anemia)
- anemia with high reticulocyte percentage indicates loss of red blood cells (hemolysis, bleeding) leading to increased compensatory production of reticulocytes (bone marrow is functional - bone marrow should be able to compensate up to 6-7 times normal hemolysis)
PERIPHERAL BLOOD SMEAR
- normal erythrocyte diameter = 7.2-7.9 mm / pink
biconcave appearance, 110-120 days lifespan - anisocytosis - variation of volume – microcytosis /
macrocytosis - poikilocytosis - variation of shapes – codocytes or target cells, spherocytes, drepanocytes or sickle cells
- anisochromia - variation of color – hypochromia,
polychromatophilia
BONE MARROW EXAMINATION
analysis of bone marrow samples obtained by bone marrow
biopsy/aspiration: performed on posterior iliac crest or sternum.
normal cellularity:
- granulocyte precursor - 75%
- red cell precursors - 23%,
- lymphocytes precursors - 1%,
- megakaryocytic precursors - less than 1%
red cell precursors proliferate and mature under the influence of erythropoietin (renal synthesized polypeptide), GM-CSF, Il3, which cause precursor proliferation and globin and hemoglobin synthesis
Perls stain (Prussian blue) reveals iron deposits in the erythroblasts cytoplasma: sideroblasts (20-50% RBC precursors)
ANEMIAS
Definition: Hemoglobin levels in the blood below the
acceptable standards for an individual of a certain age
and sex.
(hemoglobin: Hem (Fe + porphyrin) group + globin)
CLASSIFICATION OF ANEMIAS
Morphological classification (according to red cell indices / peripheral blood smear)
A.MICROCYTIC HYPOCHROMIC ANEMIA
- Iron deficiency
a) Iron deficiency anemia
b) Anemia of chronic disease
2.
Deficient synthesis of porphyrin / Hem synthase
deficiency
- Sideroblastic anemia
- Globin deficiency
- Thalassemia - quantitative deficit
B. NORMOCHROMIC NORMOCYTIC ANEMIA
- Impaired production - bone marrow aplasia (various
causes) - Anemia due to destruction or acute blood loss
a) Acute posthemorrhagic anemia
b) Hemolytic anemias
i. Intracorpuscular defects
ii. Extracorpuscular factors
C. MACROCYTIC NORMOCHROMIC ANEMIA
- Vitamin B12 deficiency
2. Folate deficiency
MICROCYTIC HYPOCHROMIC ANEMIAS
Iron Metabolism
IRON METABOLISM
Fe = 4.5 g - 72% in Hb , 25 % stored as ferritin + hemosiderin , 3% in Mb and lysosomal enzymes
Food source : red meat ( organs - liver ) , green vegetables : spinach / whole grains
Intestinal absorption : in duodenum + proximal jejunum 1-2 mg per day ( about 10% of dietary iron 10-20 mg /day ) intestinal absorption rate increases 20-50 % in iron deficiency anemia.
Dietary iron can be absorbed as part of a protein such as heme or must be ferrous Fe +2 ; DMT1 then transport the iron across the enerocyte’s cell membrane + into the cell . Here iron can be stored as ferritin or can be transported in the body with the help of ferroportin ( transmembrane protein ) found in all cells that transport or store iron
Ferroportin
is inhibited by hepcidin - “master regulator” of iron
metabolism.
Hepcidin
is regulated by iron levels and erythropoiesis. Increased iron will up regulate hepcidin which then decreases iron and vice versa.
Active erythropoiesis inhibits hepcidin (allowing iron to be absorbed/released for hemoglobin synthesis).
Hepcidin
is increased by inflammatory cytokines, particularly IL-6, and reduces available iron during inflammatory processes.
Iron form
Iron is not free in the circulation but exists bound to transferrin (βglobulin). Transferrin-bound iron (from absorption of dietary iron in the intestine or released by macrophages) binds to transferrin receptors, which are highly expressed on the surface of red cell
precursors, and is taken up into the cells where it is used to form hemoglobin.
Aging red blood cells are recognized, captured and
phagocytized by
splenic macrophages.
Iron is attached to
transferrin and transferrin-iron
complexes are then transferred into the blood, the vast
majority of iron used in hematopoiesis comes from
recycled hemoglobin.
Macrophages loaded with
iron in the liver, spleen, bone marrow store excess iron as ferritin and hemosiderin.
Daily iron losses by epithelial / endothelial scaling, sweat :
1mg Fe/day (men) 2 mg Fe / day (fertile women)
Serum transferrin
200 – 400 mg/dl
Transferrin saturation
30%
TIBC- total iron binding capacity
= 300 – 400 μg/dl
LIBC - latent iron binding capacity
200 – 300 μg/dl
Serum iron (SI)
50 – 150 μg/dl
Serum ferritin
30 – 300 ng/ml
IRON DEFICIENCY ANEMIA
belongs to hypoproliferative anemias due to impaired
maturation of erythroblasts caused by iron deficiency.
Causes
1) low iron intake (inadequate or vegetarian diet)
2) absorption disorders (gastrointestinal diseases - gastric atrophy, gastro-intestinal bypass)
3) iron losses - chronic bleeding (small and repeated):
uterine,
gastrointestinal (ulcers, gastric cancer, colon cancer)
increased needs: pregnancy, lactation
LABORATORY TESTS
IRON DEFICIENCY ANEMIA
hypochromic microcytic anemia,
Hb <12 g/dL, Ht <40% MCV <80 fl, MCHC <32 g/dl
↓ low or normal reticulocyte percentage
↓ Serum iron (SI) <50 microg / dl
↓ Transferrin saturation (<30%)
↑ Serum transferrin > 400 mg / dl
↑ TIBC - total iron binding capacity > 400microg/dl;
↑ LIBC - latent iron binding capacity >300microg/dl
↓ Serum ferritin <10 ng/ml)
TREATMENT
find and treat the cause of blood loss
oral iron (FeSO4 300 mg tid)
after 7-10 days = reticulocyte percentage = 8 – 10%
ANEMIA OF CHRONIC DISEASE
Causes
1) chronic suppurative infections:
- tuberculosis, chronic osteomyelitis,
- subacute bacterial endocarditis,
- pyelonephritis
2) chronic inflammatory diseases:
RA, SLE, vasculitis, Crohn’s disease.
3) cancers
PATHOPHYSIOLOGICAL MECHANISMS
- Chronic inflammation, by increasing the synthesis of
cytokines: Il1, IL6, increases the synthesis of hepcidin,
which inhibits ferroportin and thus the iron absorption
and the iron release from storages (iron sequestration) - Chronic inflammation inhibits erythropoietin synthesis and thus erythropoiesis
- Transferrin is an acute phase protein consumed during inflammation
LABORATORY TESTS
OF CHRONIC ANEMIA
moderate microcytic hypochromic anemia (Hb = 8-9 g/dl) but
it can be also normochromic normocytic
↓ low or normal reticulocyte percentage
↓ Serum iron (SI) <50 microg / dl
↓ Serum transferrin ;
↓ TIBC
↑ normal / high serum ferritin levels
The treatment is the treatment of the chronic disease.
SIDEROBLASTIC ANEMIA
heterogeneous group of diseases characterized by defects in the synthesis of porphyrins which lead to reduction of heme synthesis
pathognomonic: ringed sideroblasts - thick perinuclear
ring of iron granules revealed by Prussian blue
CLASSIFICATION OD SIDEROBLASTIC ANEMIAS
- Congenital sideroblastic anemia
- X-linked recessive transmission: impaired synthesis of porphyrins
- severe anemia corrected by high doses of Vit. B6 (pyridoxine)
2. Acquired idiopathic sideroblastic anemia - are considered myelodysplastic syndroms (10% evolve as acute leukemia);
- severe anemia refractory to conventional treatment including vit. B6.
3. Acquired secondary sideroblastic anemia - associatiated with medication, chemotherapy, toxics: alcohol, Pb, isoniazid, cloranfenicol, cyclophosphamide, inflammatory diseases:
RA, cancer
LABORATORY TESTS OF SIDEROBLASTIC ANEMIA
Microcytic hypochromic anemia
↑ elevated serum iron levels
↑ elevated transferrin saturation (low LIBC)
Normal TIBC, normal serum transferrin levels
↑ normal or elevated serum ferritin levels
Ringed sideroblasts on Perls stain
