Copia - Anemia

HY:Anemias

Gonzalez MD

START

Students Resources (Exam focus)

Pathophysiology - Histopathology

Clinical setting

Lippincott Illustrated Reviews: Physiology (Lippincott Illustrated Reviews Series) Adrenal Glands

Myeloid Neoplasms

Myeloid Neoplasms

Myeloid Neoplasms

Clinical indications for peripheral blood film

Suspected chronic lymphoproliferative such as chronic lymphocytic leukaemia

Severe bacterial sepsis and parasitic infections

Unexplained jaundice or haemolysis

Suspected cases of nutritional anaemia

All pregnant patients are at increased risk of anemia

Morphological characteristics of Red Blood Cells

Normal shape: A biconcave disc, a disc shaped (or circular) cell that is compressed at the centre in both directions. This allows an increased surface area for diffusion of oxygen. Typical diameter of 7.2um (normal: 6.2um and 8.2um) They contain no nucleus, to maximize volume of Hb (carriage of oxygen). They are also very flexible, useful for squeezing into thin capillaries to deliver oxygen to tissues.

red cells have a fairly uniform variation in size, with a red cell distribution width of 11–15% in normal individuals. ****Abnormal variations in sizes and shape are termed anisocytosis and poikilocytosis, respectively

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Morphological characteristics of Red Blood Cells: color and pallor

Central pallor: In healthy conditions it occupies 1/3rd of total cell diameter.

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Morphological characcteristics of Red Blood Cells

Red blood cell size : approx. same as nucleus of mature small lymphocyte (7um)

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Red blood cell size : approx. same as nucleus of mature small lymphocyte (7um)

Morphological characcteristics of Red Blood Cells

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Morphological Abnormalities of Red Blood Cells

Morphological Abnormalities of Red Blood Cells

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Variations in Size

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Variations in Size

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Variations in Size: MCV

The most important red cell index for discussing the variations in size of blood cells is the Mean Corpuscular Volume. Its reference value: 80fL – 95fL (100fL) Any variation in size of the RBCs is known as anisocytosis, and the degree of anisocytosis in a sample of blood is known as the red cell distribution width.

A varying MCVs: microcytic, macrocytic, and normocytic anemias

Utility in helping determine the etiology of anemia

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Variations in Size: MCV

The most important red cell index for discussing the variations in size of blood cells is the Mean Corpuscular Volume. Its reference value: 80fL – 95fL (100fL) Any variation in size of the RBCs is known as anisocytosis, and the degree of anisocytosis in a sample of blood is known as the red cell distribution width.

A varying MCVs: microcytic, macrocytic, and normocytic anemias

Utility in helping determine the etiology of anemia

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Variations in Size: Isocytosis

Red blood cells normally are the same size and color and are a lighter color in the center.

Abnormal results mean the size, shape, color, or coating of the red blood cells is not normal. Some abnormalities may be graded on a 4-point scale: 1+ one quarter of cells are affected 2+ one half of cells are affected 3+ three quarters of cells are affected 4+ all of the cells are affected

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Variations in Size: Isocytosis vs Anisocytosis

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

RBC calculations & indices

Calculation of the MCV value is by multiplying the percent hematocrit by ten divided by the erythrocyte count.

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Anemia approach

1. Anemia Y/N 2. Volume 3. BM FUNCTION

1. CBC:Hb (Hct) 2. SMEAR:MCV 3. BK: Ferritin & Iron Retic V.12 deficiency/ Neutroph. morphology

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Microcyte (not microcytosis - not microcytic)

A microcyte, is a red blood cell by definition, a small (micro-) mature cell (-cyte). In terms of MCV, a microcyte has an MCV below 80fL. In terms of actual diameter, a microcyte is defined as any RBC with a diameter less than 5.0 microns (average of 7.2 microns). Microcytes indicate some problem with the manufacturing system of red blood cells (deficiency). The diseases include: Iron Deficiency Anemia Sideroblastic Anemia Beta thalassemias Lead Poisoning

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Microcyte (not microcytosis - not microcytic)

Deficiency of iron leads to a scenario where the red blood cell cannot be filled with Hb and thus is an overall smaller cell, since there is less Hb. Sideroblastic Anemia (bone marrow releases immature red blood cells, sideroblasts). These sideroblasts have rings of iron around their nucleus, and thus the iron is used up on the sideroblasts causing often a defiency of iron leading to red blood cells that do mature, becoming microcytes. Beta thalassemias (the beta chain of Hb is usually missing or deformed/blockage to the HBB gene --- leads to decreased Beta-chain synthesis ---- leads to the underproduction of HBA --- Reductions in HBA to fill the red blood cells ------ in turn leads to microcytic anemia). Lead Poisoning: lead interferes with the activity of delta-aminolevulinic acid dehydratase (ALAD) and ferrochelatase, both involved in the formation of heme. Microcytosis occurs due to lack of heme, which leads to a lack of Hb and thus a deficiency, causing smaller RBCs.

B thalassemia

Beta thalassemias (the beta chain of Hb is usually missing or deformed/blockage to the HBB gene --- leads to decreased Beta-chain synthesis ---- leads to the underproduction of HBA --- Reductions in HBA to fill the red blood cells ------ in turn leads to microcytic anemia).

Lead poisoning

Lead Poisoning: lead interferes with the activity of delta-aminolevulinic acid dehydratase (ALAD) and ferrochelatase, both involved in the formation of heme. Microcytosis occurs due to lack of heme, which leads to a lack of Hb and thus a deficiency, causing smaller RBCs.

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Lead poisoning

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Iron deficiency anemia

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Classificstion

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RBC calculations & indices: Iron - Hb defects (filling defects: MCV + RDW

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Macrocyte: Immature cells --- DNA synthesis impairment

In terms of MCV, a macrocyte has an MCV above 95 (or above the reference range). It is thus an enlargement of red blood cells with a near constant concentration of hemoglobin. Megaloblastic Anemia is the most common cause of macrocytic anemia, which is the result of impaired DNA synthesis. ***Note: Although DNA synthesis is impaired, RNA synthesis is not, and RNA continues to be produced, increasing the nuclear matter within RBCs that is not being converted to DNA. Thus, the cell gradually enlarges due to increased nuclear matter, causing macrocytosis. Examples (macrocytosis): Vitamin B12 deficiency Folate deficiency (synthesis of Thymidine and Purines), and thus DNA synthesis is impaired in these deficiencies Aplastic anemia: Mild macrocytosis is seen in recovery from aplastic anemia, which occurs when there is a bone marrow pathology and a deficiency of all 3 types of blood cells (WBC, RBC, platelets) occurs.

What is a megaloblast???????

Daily folate requirement:100µg Daily B-12 requirement:1µg

ERSpublications A review of ventilation–perfusion relationships and gas exchange, basic concepts and their relation to clinical cases http://ow.ly/wMUwq

Dumping syndrome ?????

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Reticulocyte COUNT and index

The number of reticulocytes is an accurate reflection of the amount of RBC produced in bone marrow and entering the peripheral blood. It is therefore an index of effective erythropoiesis. Normal fraction is low (0.5% to 2.5% in adults and 2% to 6% in infants) because there is a homeostasis between destruction of aged abnormal RBC and a low level of marrow activity required to maintain normal hemoglobin levels

If the patient has moderate or severe anemia, the bone marrow will release reticulocytes prematurely into the blood “shift reticulocytes”, and they will circulate in the peripheral blood for longer than normally released reticulocytes. In such case a corrected count expressed as reticulocyte index or reticulocyte proliferation index to avoid spurious results.

Reticulocyte COUNT and index. Interpretation

Interpretation: RI <2% with anemia indicates decreased production of reticulocytes (i.e. inadequate response to correct the anemia) and therefore RBCs. RI >3% with anemia indicates loss of RBCs (from causes such as hemolysis, bleeding etc.) with an increased compensatory production of reticulocytes to replace the lost RBC

Reticulocyte percentage vs absolute COUNT

The absolute reticulocyte count and corrected reticulocyte percentage, as a marker of RBC production, provide an initial evaluation as to whether anemia is due to loss of RBCs or inadequate production. Increased reticulocyte count reflects ongoing or recent RBC production activity, which may result from the following:

• Post bleeding (trauma, gastrointestinal bleeding, menorrhagia)
• Post hemolysis (hemolytic anemia, hemolytic disease of the newborn)
• Response to therapy (iron supplementation, vitamin B-12 or folic acid supplementation, erythropoietin supplementation, bone marrow recovery following chemotherapy or bone marrow transplantation)

A decreased reticulocyte count reflects decreased RBC production:

• Vitamin B-12, folic acid, and iron deficiency (megaloblastic anemia, pernicious anemia, iron deficiency anemia)
• Decreased erythropoietin level (chronic renal failure)
• Aplastic anemia or bone marrow failure syndromes
• Post radiation therapy
• Bone marrow replacement by benign (metabolic storage diseases, infection, sarcoidosis) or malignant processes (leukemias, involvement by lymphomas or metastatic tumors)

Reticulocyte COUNT and index

A sample haemogram report of an adult male from an automated hematology analyser The uncorrected reticulocyte count was 3.59%, which is higher than the normal range for adults; this may give a false interpretation of an adequate reticulocyte response from the bone marrow; however, after correction for hematocrit the reticulocyte index was 2%

Poikilocytosis

Part II: Poikilocytosis