Flashcards in Chapter 2: Erythropoiesis and General Aspects of Anemia Deck (54):
What is the lineage of erythrocytes?
Hematopoietic stem cell --> CFU-GEMM --> BFU-E --> CFU-E --> Pronormoblast --> Normoblasts --> Late normoblast --> Reticulocyte --> Erythrocyte
Are nucleated normoblasts seen in the peripheral blood?
Not unless extramedullary erythropoiesis is occuring.
What is erythropoietin?
Erythropoietin is the hormone that regulate erythropoiesis.
Where is erythropoietin produced?
90% is produced in the peritubular interstitial cells of the kidney and 10% is produced in the liver and elsewhere.
What is the stimulus for the production of erythropoietin?
oxygen tension in the tissue of the kidneys. (Anything that leads to hypoxia in the kidney will stimulate erythropoietin production)
What transcription factors are activated by erythropoietin?
GATA-1 and FOG-1 are activated by erythropoietin and activate genes that are specific to erythrocytes.
What happens if erythropoietin production is not shut off and persists chronically?
Red marrow will expand first into fatty marrow and then into extramedullary sites. Marrow cavity expansion in infants may lead to bone deformities.
What down regulates erythropoietin production?
When oxygen levels in the tissue return to normal the erythropoietin drive is reduced.
When is serum erythropoietin high?
When a tumor secreting erythropoietin is causing polycythemia.
When is serum erythropoietin low?
Severe renal disease and polycythemia rubra vera both cause low erythropoietin
When is erythropoietin given therapeutically?
(1) End-stage renal disease
(2) Autologous blood transfusions
(3) Anemia of chronic disease
(4) Myelodysplasia or Myeloma
What differentiates Reticulocytes from erythrocytes?
Reticulocytes still have RNA and protein synthesis machinery in the cytoplasm.
What is often given with therapeutic erythropoietin to improve its effect?
Iron supplements are often administered with therapeutic erythropoietin.
What are some adverse reactions associated with erythropoietin therapy?
Adverse side effects are a rise in blood pressure and platelet count and local injection site reactions.
What are some precursors required for erythropoiesis?
Iron, cobalt, vitamin B12, folate, vitamin B6, vitamin C, Vitamin E, thiamine, riboflavin, androgens, and thyroxine.
What is the structure of the dominant adult hemoglobin?
Hb A has 2 alpha chains and 2 beta chains with a heme group.
When do erythrocytes switch from fetal to adult hemoglobin?
At about 3-6 months after birth.
Where does heme synthesis occur?
Heme synthesis occurs in the mitochondria and begins with the condensation of glycine and succinyl CoA.
What is the rate limiting enzyme in heme synthesis?
ALA-Synthase (aminolaevulinic acid synthase)
What coenzyme is important for heme synthesis?
vitamin B6 (pyridoxal phosphate)
How does hemoglobin's structure relate to its function?
When oxygen binds hemoglobin the molecule is stabilized by the contacts between the various parts of the hemoglobin molecule. When oxygen dissociates from hemoglobin the beta chains of the hemoglobin are pulled apart and 2,3-DPG binds to hemoglobin decreasing the overall affinity of the molecule for oxygen.
What is the normal arterial oxygen saturation?
95% with a mean O2 tension of 95mmHg
What is the normal venous oxygen saturation?
70% with a mean O2 tension of 40mmHg.
How does high 2,3-DPG, H+ ions, and CO2 effect a hemoglobin curve?
They shift the curve to the right (oxygen is given up more easily by hemoglobin)
Why does fetal hemoglobin have a higher affinity for oxygen than adult hemoglobine?
Because it does not bind 2,3-DPG.
What is Methhemaglobinemia?
Methhemaglobinemia is a state in which heme carries iron in the oxidized Fe3+ state instead of the normal Fe2+ state. The result is usually cyanosis. (can be from NADH deficiency or mutated hemoglobin or toxicity)
What is the Embden-Meyerhof pathway?
The EM pathway is a series of biochemical reactions that metabolize glucose to lactate (anaerobic metabolism)
Why is the Embden-Meyerhof pathway essential for Red cell function?
Because ATP is need to maintain the red cell shape/flexibility and to maintain the sodium/potassium gradients across a leaky membrane. Additionally the NADH produced reduces Fe3+ methhemaglobin to Fe2+ hemaglobin, and helps to produce 2,3-DPG.
Why is the pentose phosphate shunt important to RBCs?
Because it produces NADPH which is important for heme iron reduction and maintenance of the RBC membrane.
What proteins form an integral part of the RBC cytoskeleton?
What is anemia?
Anemia is a reduction in the hemaglobin concentration in the blood.
What is the adult cutoff for Anemia?
Hb less than 13.5g/dL in adult males.
Hb less than 11.5g/dL in adult females.
What is the cutoff for anemia between the ages of 2 to puberty?
Hb less than 11g/dL
What is the cutoff for anemia in infants?
Hb less than 14g/dL
What blood test findings often accompany reduced hemaglobin?
decreased RBC count and decreased packed cell volume (PCV).
How is blood plasma volume related to anemia?
increased or decreased plasma volume can lead to changes in the hemaglobin and RBC concentrations.
What are the clinical features of anemia?
(1) increased stroke volume
(3) Altered O2 dissociation curve
What four factors most influence the clinical manifestations of anemia?
(1) Speed of onset
(4) Haemaglobin O2 dissociation curve.
How doe speed of onset effect the clinical manifestations of anemia?
Rapid onset causes more severe symptoms compared with less rapid onset because there is less time for cardiovascular compensation.
How does severity effect the clinical manifestations of anemia?
Mild anemias not lower than 9-10g/dL Hb often do not show substantial signs or symptoms. Although, even lower values may show few symptoms in healthy patients.
How does the Hemoglobin O2 dissociation curve impact the clinical manifestations of anemia?
In response to anemia the body will alter the dissociation curve of hemoglobin by producing more 2,3-DPG or by producing the lower affinity Hb S.
What are the symptoms of anemia?
Sob (often with exercise), weakness, lethargy, palpitation, headaches. Sometimes older patients exhibit signs of cardiac failure. Occasionally retinal hemorrhages may occur in more severe cases.
What are the signs of Anemia?
General signs include pallor of mucus mambranes, hyperdynamic circulation, tachycardia, cardiomegaly, and a systolic flow murmur at the apex. Other signs are specific for particular kinds of anemias.
What are the Red cell classifications for anemia?
Anemia can be classified as microcytic, normocytic, or macrocytic depending on the Red cell indices.
Under what normal conditions is the MCV (mean corpuscular volume) elevated
MCV may be high briefly in the newborn and during pregnancy.
Why are leukocyte and platelet counts useful when anemia is suspected?
They are useful for differentiating between anemia and pancytopenia ( a drop in the numbers of all blood cells)
In what anemias may the leukocyte and platelet counts be raised?
In anemias due to hemolysis, hemorrhage, infection, or leukemias the platelet and Leukocyte counts are often raised.
What is the normal range for a reticulocyte count?
.5-2.5% or 25-125x10^9 cells per liter. Will be higher during anemia due to erythropoietin.
What is the timeline for erythropoietin release?
In acute hemorrhage the erythropoietin response is seen in about 6h, the reticulocyte count rises within 2-3 days, and peaks around 6-10 days.
What is a blood film used for?
Blood films are used to examine the morphological appearance of blood cells. This may be useful in the diagnosis of anemias and other disorders.
Why is erythropoiesis considered inefficient?
Because 10-15% of erythroblasts die in the marrow without producing any mature erythrocytes. Some anemias show an increased inefficiency of erythropoiesis.
How can the effectiveness of erythropoiesis be evaluated?
By examination of the bone marrow, hemaglobin levels, and reticulocyte levels.
How is total erythropoiesis assessed?
By examining the cellularity of the marrow for the myeloid:erythroid ratio (which is normally 2.5:1 to 12:1)