Erythrocyte Development Flashcards
Anemia is the most common disorder or the blood with 3 classes
excessive blood loss
excessive destruction
deficient production
When does Hemoglobin synthesis begin?
Hemoglobin synthesis begins at the early erythroblast stage
Erythropoietin
Acts in the bone marrow by binding to receptors on committed stem cells
Promote hemoglobin synthesis, increases membrane proteins, and causes differentiation of erythroblasts.
We can make it too!
What is the most important function of the erythrocyte?
To transport hemoglobin (which is enclosed in red blood cells), which in turn carries oxygen from the lungs to the tissues
What happens when hemoglobin formation is deficient?
When hemoglobin formation is deficient (as in iron deficiency for example), the percentage of hemoglobin in the cells may fall considerably, and the volume of the red cell may decrease
Hemoglobin A
the normal hemoglobin
molecule found in adults
2 alpha chains + 2 beta chains => Hemoglobin A molecule
Life Span of Erythrocyte
RBC is delivered from the bone marrow into circulatory system, circulates an average of 120 days before being destroyed
metabolic systems become progressively less active, and the cells become more fragile
When cell is fragile it can rupture during passage through some tight spot of the circulation
Many red cells self destruct in the spleen (spaces in the red pulp of spleen are very small, 3 micrometers wide versus 8 micrometer diameter of red cell)
Destruction of Hemoglobin
RBC’s burst and release hemoglobin, the hemoglobin is phagocytized almost immediately by macrophages (especially by Kupffer cells of the liver and macrophages of the spleen and bone marrow)
Then, the macrophages release iron from the hemoglobin and pass it back into the blood, where it is carried by transferrin to either:
bone marrow for production of new red blood cells
liver and other tissues for storage in the form of ferritin
the porphyrin portion of the hemoglobin molecule is converted into the bile pigment bilirubin, which is released into the blood and later removed from the body by secretion through the liver into the bile
Two main types of hemoglobinopathies can cause red blood cell hemolysis
- Abnormal substitution of an amino acid in the hemoglobin molecule, as in sickle cell anemia
- Defective synthesis of one of the polypeptide chains that form the globin portion of hemoglobin, as in the thalassemias
Sickle Cell Disease
Results from point mutation in Beta chain of hemoglobin molecule, with abnormal substitution of a single amino acid, valine, for glutamic acid.
Sickle hemoglobin (HbS) is transmitted by recessive inheritance and can manifest as:
Sickle cell trait (heterozygote with one HbS gene)
Sickle cell disease (homozygote with two HbS genes)
Sickle Cell Disease Pathophysiology
At low oxygen tension HbS becomes sickled
Sickling occurs as a result of the formation of elongated crystals inside the red blood cells (can be as long as 15 micrometers in length)
Sickling causes two major problems
- Makes it almost impossible for the red blood cell to pass through many small capillaries
- Spiked end of crystals rupture membranes, leading to sickle cell anemia
Acute chest syndrome
atypical pneumonia resulting from pulmonary infarction
Acute Chest Syndrome is a leading cause of death in sickle cell disease
Alpha-Thalassemia
Impaired production of alpha globin chains, which leads to excess of beta globin chains
Asians
Synthesis is controlled by two pairs of genes
Silent carriers have a deletion of a single alpha-globin gene and are asymptomatic
Deletion of two genes (Alpha thalassemia trait)? Mild hemolytic anemia
Deletion of all 4 genes? Death
Beta-Thalassemia
Impaired production of beta globin chains, which leads to a variable excess of alpha globin chains.
Most prevalent
Mediterranean anemia
One normal gene in heterozygous persons (Thalassemia minor)? => usually results in sufficient normal hemoglobin synthesis to prevent severe anemia
Homozygous persons (Thalassemia major)? => severe, transfusion-dependent anemia that is evident at 6-9 months of age
Deficiency of G6PD
The disorder makes red blood cells vulnerable to oxidants and causes them to denature forming Heinz Bodies
Carbon Monoxide
CO binds to hemoglobin with much greater affinity than oxygen (which is not good!), forming carboxyhemoglobin (COHb) and resulting in impaired oxygen transport and utilization
Lead Toxicity
Lead is stored in bone and eliminated by the kidneys
Toxicity:
Inactivates enzymes
Competes with calcium for incorporation into the bone
Interferes with nerve transmission and brain development
THE MAJOR TARGETS OF LEAD TOXICITY:
RBCs
GI tract
Kidneys
Nervous system
Lead toxicity smear
RBCs smaller than normal-Increased zone of central pallor
Basophilic stippling on blood smear
The cardinal sign of lead toxicity
ANEMIA
Lead competes with the enzymes required for hemoglobin synthesis
Resulting RBCs are MICROCYTIC and HYPOCHROMIC (similar to iron deficiency anemia)
LEAD TOXICITY-SYMPTOMS / SIGNS
GI tract is the main source of symptoms
“Lead line”
Diffuse Kidney damage
Nervous System
Normochromic Anemia
Concentration of hemoglobin in the cell is in the normal range
However, there are not enough red blood cells
Includes aplastic, post-hemorrhagic, hemolytic anemias, and anemia of chronic disease
Most frequent type of anemia
Hypochromic Anemia
Red blood cells are pale Increased central pallor HgB is what adds the red pigment Red Blood Cells are also usually small Fe deficient Anemia and Thallasemia
Microcytic Anemia
Small Red Blood Cells
MCV Decreased
Also, MCHC, because usually goes with hypochromic
And……Fe deficiency and Thallasemia
Macrocytic Anemia
Red Blood Cells are large
Hemoglobin also down
Folate, B12, Codocytes (target cells)
Anisocytosis
RBCs are of unequal size
RDW
FE DEFICIENCY ANEMIA AND THALLASEMIA
Poikilocytosis (Erythrocytosis)
Abnormal shaped RBCs
Flattened disks that are thinner in the middle than at the edges
Abnormal if make up >10%
Membrane abnormalities and trauma
