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Pathophysiology Lp > 09. Blood count , Class. of Anemia , Iron Metabolsim ,Microcytic Hypochromic Anemia > Flashcards

09. Blood count , Class. of Anemia , Iron Metabolsim ,Microcytic Hypochromic Anemia Flashcards

1
Q

Blood count

A

brings information about
platelets,
leukocytes,
erythrocytes (RBC).

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2
Q

PLATELETS

A

normal values: 150,000 – 450,000/mmc

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3
Q

WHITE BLOOD CELLS

A

normal values: 4,000 - 10,000/mmc

Leukocyte formula:

Neutrophils 30-60%

Lymphocytes 20-50%

Monocytes 2-10%

Eosinophils 0-5%

Basophils 0-1%

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4
Q

TYPE OF LEUKOCYTES

INCREASED

A

POSSIBLE CAUSES - look at the lp

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5
Q

LEUCOPENIA
< 4,000/MMC

TYPE OF LEUKOCYTE
DECREASED

A

POSSIBLE CAUSES - look at the lp

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6
Q

ERYTHROCYTES (RED BLOOD CELLS)

Basic Parameters:

A
  1. Hemoglobin
  2. Red blood cells count
  3. Hematocrit
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7
Q

Erythrocyte Indices:

A

MCV
MCH
MCHC

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8
Q

HEMOGLOBIN (HB)

A

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

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9
Q

ANEMIC SYNDROME

A

= 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

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10
Q

RED BLOOD CELLS COUNT

A

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

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11
Q

HEMATOCRIT (HT)

A
  • 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% ;
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12
Q

MCV ( Mean Corpuscular Volume )

A

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

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13
Q

MCH (MEAN CORPUSCULAR HEMOGLOBIN)

A

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

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14
Q

MCHC (MEAN CORPUSCULAR HEMOGLOBIN

CONCENTRATION)

A
  • 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
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15
Q

RETICULOCYTES

A
  • 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)
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16
Q

PERIPHERAL BLOOD SMEAR

A
  • 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
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17
Q

BONE MARROW EXAMINATION

A

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)

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18
Q

ANEMIAS

A

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)

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19
Q

CLASSIFICATION OF ANEMIAS

A 
Morphological classification (according to red cell
indices / peripheral blood smear)
20
Q

A.MICROCYTIC HYPOCHROMIC ANEMIA

A
  1. Iron deficiency

a) Iron deficiency anemia
b) Anemia of chronic disease

2.
Deficient synthesis of porphyrin / Hem synthase
deficiency
- Sideroblastic anemia

  1. Globin deficiency
    - Thalassemia - quantitative deficit
21
Q

B. NORMOCHROMIC NORMOCYTIC ANEMIA

A
  1. Impaired production - bone marrow aplasia (various
    causes)
  2. Anemia due to destruction or acute blood loss
    a) Acute posthemorrhagic anemia
    b) Hemolytic anemias
    i. Intracorpuscular defects
    ii. Extracorpuscular factors
22
Q

C. MACROCYTIC NORMOCHROMIC ANEMIA

A
  1. Vitamin B12 deficiency

2. Folate deficiency

23
Q

MICROCYTIC HYPOCHROMIC ANEMIAS

A

Iron Metabolism

24
Q

IRON METABOLISM

A

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

25
Q

Ferroportin

A

is inhibited by hepcidin - “master regulator” of iron

metabolism.

26
Q

Hepcidin

A

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).

27
Q

Hepcidin

A

is increased by inflammatory cytokines, particularly IL-6, and reduces available iron during inflammatory processes.

28
Q

Iron form

A

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.

29
Q

Aging red blood cells are recognized, captured and

phagocytized by

A

splenic macrophages.

30
Q

Iron is attached to

A

transferrin and transferrin-iron
complexes are then transferred into the blood, the vast
majority of iron used in hematopoiesis comes from
recycled hemoglobin.

31
Q

Macrophages loaded with

A

iron in the liver, spleen, bone marrow store excess iron as ferritin and hemosiderin.

32
Q

Daily iron losses by epithelial / endothelial scaling, sweat :

A

1mg Fe/day (men) 2 mg Fe / day (fertile women)

33
Q

Serum transferrin

A

200 – 400 mg/dl

34
Q

Transferrin saturation

A

30%

35
Q

TIBC- total iron binding capacity

A

= 300 – 400 μg/dl

36
Q

LIBC - latent iron binding capacity

A

200 – 300 μg/dl

37
Q

Serum iron (SI)

A

50 – 150 μg/dl

38
Q

Serum ferritin

A

30 – 300 ng/ml

39
Q

IRON DEFICIENCY ANEMIA

A

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

40
Q

LABORATORY TESTS

IRON DEFICIENCY ANEMIA

A

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)

41
Q

TREATMENT

A

find and treat the cause of blood loss

oral iron (FeSO4 300 mg tid)

after 7-10 days = reticulocyte percentage = 8 – 10%

42
Q

ANEMIA OF CHRONIC DISEASE

A

Causes

1) chronic suppurative infections:
- tuberculosis, chronic osteomyelitis,
- subacute bacterial endocarditis,
- pyelonephritis

2) chronic inflammatory diseases:
RA, SLE, vasculitis, Crohn’s disease.

3) cancers

43
Q

PATHOPHYSIOLOGICAL MECHANISMS

A
  • 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
44
Q

LABORATORY TESTS

OF CHRONIC ANEMIA

A

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.

45
Q

SIDEROBLASTIC ANEMIA

A

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

46
Q

CLASSIFICATION OD SIDEROBLASTIC ANEMIAS

A
  1. 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
47
Q

LABORATORY TESTS OF SIDEROBLASTIC ANEMIA

A

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

Pathophysiology Lp (7 decks)

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