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Hematology%20Physiology%201%20Erythropoiesis
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Title: Hematology%20Physiology%201%20Erythropoiesis
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Hematology Physiology 1Erythropoiesis
- Brenda Beckett, PA-C
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Terms to Understand
- Hematopoiesis
- Erythropoiesis
- Pluripotent hematopoietic stem cell (PHSC)
- Committed stem cell (progenitor cell)
- Differentiation
- Maturation
- Self-renewal
- Proliferation
- Reticulocyte
- Polychromasia
- Normocyte
- Erythropoietin
- Adult hemoglobin
- Fetal hemoglobin
- Apotransferrin
- Transferrin
- Apoferritin
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Terms, continued
- Ferritin
- Hemosiderin
- Serum iron
- Total iron binding capacity
- ?-thalassemia
- ?-thalassemia
- Hemoglobinopathy
- Anemia
- Porphyria
- A,B,O,Rh blood types
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Red Blood Cell
- Transports hemoglobin
- Carries oxygen from lungs to tissues
- Carries CO2 back to lungs
- Biconcave disc
- Able to change shape
- Has excess membrane
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Red Blood Cell
- Mature RBC has no nucleus
- 5,200,000 (males), 4,700,000 (females) per cubic
milliliter - Lifespan of 100-120 days
- Derived from pleuripotent hematopoietic stem
cells (PHSC)
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PHSC
- Retained in bone marrow
- Reproduction controlled by growth inducers
- Differentiation controlled by differentiation
inducers - Will become committed stem cell (progenitor cell)
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Erythropoiesis
- Decreased O2 in tissues causes increased
production of erythropoietin - Hormone
- Formed in kidney (80-90) and liver
- Occurs in fetal liver and spleen, then shifts to
fetal bone marrow - Occurs in axial skeleton and proximal end of long
bones in adults
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Reticulocytes
- Final cell produced in marrow before release
- Basophilic remnants of endoplasmic reticulum
remain, becomes mature RBC (normocyte) within one
day - Normally 1 of total RBCs
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Reticulocyte Count
- Can differentiate between anemias due to
decreased production and those of increased
destruction - Will see polychromasia on Wrights stain, need to
order separate test for reticulocyte count
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Hemoglobin Formation
- Begins at proerythroblast stage, continues until
reticulocyte (before leaving bone marrow) - Heme molecule combines with globin (long peptide
chain) to form hemoglobin chain. - 4 chains bind together to form hemoglobin
molecule.
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Hemoglobin
- Binds loosely and reversibly with O2
- Oxygen atom binds loosely with iron atom in
hemoglobin - Bound as O2, released as dissolved O2
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Iron Metabolism
- Iron important part of hemoglobin, myoglobin and
other structures - 65 of total iron in hemoglobin
- 4 myoglobin
- 1 various heme compounds
- 0.1 in plasma combined with transferrin
- 15-30 stored in liver as ferritin
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Iron Transportation Storage
- Absorbed in small intestine
- Binds with apotransferrin (?globulin) to form
transferrin loosely bound - Excess deposited in liver and bone marrow
- In liver, combines with apoferritin to form
ferritin. - Also stored as insoluble hemosiderin iron
overload
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Iron Usage
- If plasma iron low, iron removed from ferritin,
transported as transferrin in plasma - Transferrin binds strongly with cell membranes on
erythroblasts in marrow - Ingested, delivered to mitochondria
- Heme synthesized
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Globin chains
- 4 globin chains combine with heme to make
hemoglobin molecule - 95-97 of adult hgb has 2 ?-chains and 2 ?-chains
(?2?2) aka Hgb A - Fetal hgb (Hgb F) has ?2?2. High O2 affinity,
mostly changes to HgbA by birth - Hgb A2 (?2?2), 3-5 of adult
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Abnormal Hemoglobins
- Hemoglobinopathies hemoglobin chains are
abnormal - Thalassemias hemoglobin chains normal in
structure but decreased or absent. Named for
which chain is affected. - Genes are on chromosomes 11 16
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Anemia
- Qualitative or quantitative deficiency of
hemoglobin - Significant blood loss
- Plasma replaced in 1-3 days
- RBCs replaced in 3-4 weeks
- Hemolysis
- Deficient RBC production
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Vitamin B12/Folate
- Important for final maturation of RBCs
- Essential to synthesize DNA
- Decrease in either leads to failure of nuclear
maturation and division - RBCs also become larger, irregular shape, flimsy
membrane - Carry O2 normally, have short lifespan
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Vitamin B12/Folate Deficiency
- Macrocytic or megaloblastic anemia
- Pernicious anemia inability to absorb Vitamin
B12 from GI tract - Gastric mucosa secretes Intrinsic Factor (IF),
combines with B12, available for absorption - B12 stored in liver and bone marrow
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Iron deficiency
- When iron stores are depleted, stored iron is
mobilized - When iron stores drop, hemoglobin synthesis is
affected iron deficient erythropoiesis.
(hypochromic) - More severe, leads to decreased erythropoiesis,
smaller cells (microcytic)
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Iron Deficiency Anemia
- Low iron stores low Ferritin
- Low circulating iron (transferrin) low Serum
Iron - Leads to increased Total Iron Binding Capacity
(TIBC) - Hypochromic, microcytic anemia
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Anemia of Chronic Disease
- Most likely due to inflammation
- Iron stores arent released
- Decreased erythropoiesis
- Upregulation of WBC production causes decreased
erythropoiesis - Normocytic or microcytic
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Hemolytic anemias
- RBCs are fragile, shorter lifespan
- Rupture as pass through capillaries and spleen
- Hereditary or acquired (immune mediated)
- Increased destruction leads to increased
bilirubin (jaundice)
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Hemolytic anemias
- Hereditary spherocytosis (and others)
- Cells are spherical, cant withstand compression
easily ruptured - Sickle cell anemia
- Abnormal Hgb S (on ? chain)
- Exposed to low O2, forms crystals, elongates cell
sickle - Sickle trait protective against malaria
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Thalassemias
- Autosomal recessive, Mediterranean
- Reduced synthesis of one globin chain, leads to
microcytic anemia - ? or ? chain affected
- Can coexist with hemoglobinopathies
- Carrier state can be protective against malaria
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G6PD Deficiency
- Hereditary
- Low levels of G6PD (enzyme)
- Certain triggers lead to hemolysis, anemia,
jaundice - Foods, medications, infection
- Protective against malaria
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Polycythemia
- Increased number of RBCs primary or secondary
- High altitude physiologic polycythemia
- Cardiac failure, smoking, tumors
- Polycythemia vera blast cells continue to
produce RBCs even though there are too many in
circulation. Viscous blood. Treatment phlebotomy
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Porphyria
- Inherited or acquired
- Disorder of enzymes in heme pathway
- 7 different types
- Different combos of elevated porphyrins (heme
precursors) in tissues - Excreted in urine and stool
- Sx photosensitivity, abd pain, port wine urine,
muscle weakness, behavior changes
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RBC/Hemoglobin destruction
- Changes to plasma membranes as cell ages
- Recognized by phagocytes
- Phagocytosis in spleen
- Heme broken down into iron biliverdin
- Biliverdin converted to bilirubin
- Iron bound to transferrin
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Effects of anemia
- Lack of oxygen in tissues
- Symptoms can be vague
- Weakness, fatigue, malaise
- Dyspnea
- Pallor
- Increased cardiac output plapitations, heart
failure
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Blood Groups ABO
- AB antigens agglutinogens on RBC
- Anti-A /or Anti-B develop in absence of antigens
- Will agglutinate RBCs, lyse, leads to renal
failure, death
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Rh Typing
- Other antigens can be present on RBCs
- Antibodies develop if exposed to antigen
- D (Rh), d, C, c, E, e
- Erythroblastosis fetalis
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WBC
- The overall concentration of white blood cells of
all types in the blood, expressed as thousands of
cells per cubic millimeter (mm3) of blood. The
terms used to describe a decreased and an
increased WBC are leukopenia and leukocytosis,
respectively.
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RBC
- The concentration of erythrocytes in the blood,
most commonly expressed as millions of cells per
cubic millimeter (mm3). The terms describing a
decreased and an increased RBC are
erythrocytopenia and erythrocytosis,
respectively, or, more commonly, anemia and
polycythemia.
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HGB/HCT
- The overall concentration of hemoglobin in the
blood, expressed as grams of hemoglobin per 100
milliliters of blood. - The hematocrit, the percentage of the blood
volume consisting of red cells, expressed as a
percent ().
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MCV
- mean corpuscular volume, the average volume of
individual erythrocytes in a blood sample,
expressed as femtoliters (fl) per cell. One
femtoliter is the equivalent of 10-15 liters.
The terms used to describe an erythrocyte with a
normal, decreased, or increased cell volume are
normocyte, microcyte, and macrocyte,
respectively.
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MCHC
- mean cell hemoglobin concentration, the average
concentration of hemoglobin within erythrocytes,
expressed as grams of hemoglobin per dL of cells.
Because the intracellular hemoglobin
concentration determines the density of color
(suffix -chromia) of erythrocytes on a stained
blood smear, the morphological descriptions
associated with a normal, increased or decreased
MCHC are normochromia, hyperchromia and
hypochromia, respectively.
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MCH
- mean cell hemoglobin, the average quantity of
hemoglobin in individual erythrocytes, expressed
as picograms (pg) per cell. One picogram is the
equivalent of 10-12 grams.
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RDW
- red cell distribution width, expressed as the
coefficient of variation around the mean cell
volume (MCV). The larger the value for RDW, the
greater the variability in size within the
erythrocyte population. The morphological
correlate of an increased RDW is variation in the
diameters of individual erythrocytes seen on the
peripheral smear, or anisocytosis.
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PLT/MPV
- the concentration of platelets in the peripheral
blood, expressed as thousands of platelets per
cubic millimeter (mm3) of blood. - mean platelet volume, the average volume of
individual platelets, expressed as cubic microns
per platelet or as femtoliters per platelet.
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RETIC
- the reticulocyte percentage, or the percentage of
immature erythrocytes in a peripheral blood
sample. These immature cells usually constitute
from 0.5 to 1.5 of the circulating red blood
cell population. An absolute reticulocyte count,
expressed as millions of cells per cubic
millimeter (mm3), can be obtained by multiplying
the RBC by the reticulocyte percentage.
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