Hemolytic Anemia Flashcards
(37 cards)
Erythropoietin
Growth factor produced by kidneys that goes to red bone marrow and stimulates hemopoiesis
Changes that occur during erythropoiesis in RBCs
Cellular and nuclear volume of cells decreased (normal center is 1/3 diameter of total size)
Number of polyribosomes decrease while number of hemoglobin increases
- changes from purple to pink/red over time
Mitochondria and other organelles gradually dissolve
What is the normal percentage of reticulocytes in the total RBCs in the blood
1- 2.5%
Types of cell stages in the maturation of a red blood cell
Proerythroblast -> basophilic erythroblast -> polychromatophillic erythroblast -> orthochromatophillic erythroblast -> reticulocyte -> erythrocyte
Normal hematocrit percentages for men and women
Men = 39-39%
Women = 33=43%
Most common acute anemia characteristics
Weakness, fatigue, pale/cyanosis, dyspnea upon mild exertion
Hemolytic anemia broad definition
Group of disorders that all feature accelerated red cell destruction
- shortened life span from 120 days
- increased levels of erythropoietin and increased level of reticulocytes
- hyperplastic erythroids and reticulocytosis (increased level of reticulocytes) are the hallmarks of all hemolytic anemia’s*
How are most red blood cells destroyed in hemolytic anemia’s?
Extravascular hemolysis via uptake from phagocytes in the spleen
- they cant get through the splenic cords and sinusoids
- if chronic, produces splenomegaly*
Common clinical features of extravascular hemolytic hemolysis
Anemia, splenomegaly and jaundice
Decreases in plasma haptoglobin and iron levels
Intravascular hemolysis vs extravascular hemolysis
Intravascular = red cells burst spontaneously within blood
Extravascular = red cells are engulfed via phagocytes (typically in spleen) and destroyed this way.
Common clinical signs of intravascular hemolytic anemia’s
Higher levels of hemoglobinemia, hemoglobinuria and hemosiderinuria
Decreased serum haptoglobin and iron levels
Hereditary spherocytosis
Inherited defects in red blood cell skeletal membranes that lead to the formation of dark, spherical forms of red blood cells
- this form is highly proved to poor circulation movement and absorption via phagocytes in the spleen (EXTRAVASCULAR HEMOLYTIC)
- primary membrane protein that is dysfunctional in this disorder is SPECTRIN and ANKYRIN
- autosomal dominant trait
- clinical symptoms*
- normal anemia symptoms
- increases reticulocyte count
- normal-decreased MCV and hyperplastic RBCs
- gallstones (40-50% of affected people)
- splenomegaly and jaundice
What are the skeletal membrane proteins fo RBCs that are commonly affected during hereditary spherocytosis?
Spectrin, ankyrin, band 3 are the most common 3 proteins affected
Band 4.2, 4.1 proteins are less common but still possible
In all cases, these mutations in the protein(s) causes weakened interactions and causes decreases are-to-volume ratio in the RBC as it transforms into a spherical shape from a biconcave disc
Why is splenectomy so common as a treatment for hereditary spherocytosis?
Spherocytes usually are caught and destroyed in the splenic cords to prevent blockage, so by eliminating the spleen, the anemia will be less severe overall
- there is no drug treatment for hereditary spherocytosis*
Why do blood cells in hereditary spherocytosis lyse spontaneously in hypotonic solutions?
Because of the decreased protein interactions in the RBC membranes, the spherical shape of RBCs cannot expand well in hypotonic solutions, they lose much quicker than the normal biconcave shapes
What causes aplastic crisis with hereditary spherocytosis?
Parvovirus B19 infections
- virus infects erythroblasts in bone marrow and lysis them which makes the anemia even worse
- until the immune system gets the infection under control (10-14 days) the marrow may be completely devoid of RBC progenitors and cause a rapid worsening of anemia
- parvovirus infections are marked by lymphocytes in this red bone marrow*
Glucose-6-Phosphate Dehydrogenase deficiency
Causes a reduced glutathione (GSH) levels.
- the goal of this molecule is to protect the RBC against oxidants that they are commonly exposed to and would cause hemolysis if not able to be protected by
(INTRAVASCULAR HEMOLYSIS)
Is an x-linked recessive trait (males at highest risk)
Most common variant of G6PD deficiency is G6PD A- (causes decreased half-life of RBCs but normal function when alive )
Difference between G6PD A- and G6PD Mediterranean strands of G6PD deficiencies
G6PD A- = RBCs are given enzymes to produce glutathione at birth, but do not maintain the enzyme levels so they so RBCs die quicker (shorter half-life)
Mediterranean =. Enzymes are never produced so the RBCs die even quicker and some die at birth (very short half-life)
Examples of oxidative stress of RBCs
Infections (exposure to phagocytes and macrophages which use ROS)
Incriminated drugs (asprin, sulfonamides, nutrofurantonin, etc. )
Exposure to hydrogen peroxide for any reason
What is the hall mark sign of G6PD deficiency?
Heinz bodies: (oxidized hemoglobin that is denatured and precipitates)
- causes RBCs that appear to have a bite taken out of them
Paroxysmal Nocturnal hemoglobinura
PIGA gene deficiency (codes for GPI tails which serve as a membrane anchor for many proteins in the RBCs) that causes deficenty in 3 proteins
- CD55
- CD59 most important
- C8 binding
Very very rare
normal cells only have one active PIGA gene, so if you have paroxysmal nocturnal hemoglobinuria, half the cells will express the dysfunctional gene
What cells do the mutations of PIGA occur in?
Hematopoietic stem cells
- white, red and platelet cells are all affect, however RBCs are the most commonly affected and sensitive to the dysfunction
Pathogenesis of paroxysmal nocturnal hemoglobinuria
PIGA gene causes deficiency of CD55, CD 59 and C8 binding proteins
CD59 is most important since it inhibits C3 convertase binding to RBCs and initiating spontaneous alternative complement pathways
Is a INTRAVASCULAR HEMOLYSIS because without these proteins (especially CD59) MAC compliment complex binds to RBCs and lysis the cells within the circulation
Why is PNH called nocturnal?
Complement fixation is enhanced during night since your blood naturally becomes more acidic. (Caused by CO2 retention)
