Disorders of RBCs Flashcards
Where does hematopoiesis occur in the fetus at 3 weeks, 3 months, and the third trimester
At 3 weeks, in the yolk sac
3 months, kidney
3rd trimester, occurs in the bone marrow
What type of bone has hematopoietic marrow and where is it contained?
Spongy bone in the intratubular space
What is the formula to determine cellularity of the bone marrow?
100%-age
What is erythropoietin and where is it produced?
A growth factor that stimulates differentiation of red blood cells, made in the kidney
What is the name for the cell in the last stage of RBC production in the bone marrow?
Orthochromatic erythroblast
A reticulocyte will show what kind of staining? Due to?
Polychromatic staining due to RNA machinery
What is hematocrit?
The volume of red blood cells per unit of blood expressed as a percentage
What are the two ways of classifying anemia?
Red cell morphology and underlying mechanism
What are the two mechanisms for anemia?
Increase in RBC loss or decrease in production
Where does RBC destruction occur in extravascular hemolysis?
Spleen and liver
What causes intravascular hemolysis, is it more or less common than extravascular?
mechanical forces or biological agents, less common
What substance levels change in intravascular hemolysis?
Increased lactate dehydrogenase and decreased haptoglobin
What is immunohemolytic anemia?
When there is premature destruction of RBCs due to antibodies binding to them
What test is used to determine one has hemolytic anemia?
The Coombs test
What are the two types of immunohemolytic anemia?
Warm and cold antibody
In the warm type what Ig is present? At what temperature are they active?
IgG, 37 degrees C
What is the primary cause of the warm type?
Idiopathic
Which drugs can cause the warm type?
Penicillin and alpha-methyldopa
How do you treat the warm type?
Intravenous Ig, prednisone, and splenectomy as a last resort
In the cold type, what Ig is present? Describe the mechanism for this disease?
IgM, the IgM causes C3b to bind to the RBCs. When the RBCs reach warmer areas of the body the IgM is lost but the C3b remains which activates the complement system. The RBCs are then destroyed in the spleen and liver
Acute and chronic cases of the cold type are associated with?
Acute with infectious agents, chronic with lymphoma or they can be idiopathic
What are the sites for bone marrow biopsy?
The tibia in neonates and the sternal crest in adults
What is the most common hereditary hemolytic anemia in the world?
Sickle cell anemia
What causes sickle cell?
A point mutation on the 6th position of the beta globin gene substituting a valine for a glutamate
Autosplenectomy as seen in sickle cell leads to increased susceptibility to infection by?
Encapsulated organisms
What is the most common cause of death in children with sickle cell?
Septicemia and meningitis
What leads to an aplastic crises in those with sickle cell?
Transient cessation of erythropoiesis due to infection of erythroid progenitor cells by parovirus B19
What can be used to raise HbF levels and reduce the symptoms of aplastic crises?
Hydroxyurea
What causes thalassemias?
Genetic defects leading to decreased synthesis of either the alpha or beta chains of HbA
What happens to the production of the unaffected chain?
It exists in relative excess
Where is thalassemia endemic?
To areas where malaria is common such
What happens in beta thalassemia?
In beta zero there is no production of the beta chain and in beta plus there is decreased production
Describe the pathogenesis of beta thalassemia
Alpha chains aggregate and Hb level decreases as a result, RBCs are then destroyed by the spleen, systemic iron overload is possible
What are the 4 types of alpha thalassemia?
Silent carrier is when there is one gene for the alpha chain missing
Alpha thalassemia trait is when two genes are missing
Hemoglobin H disease is when 3 are missing
Hydrops fetalis is when 4 are missing (the fetus will usually die in utero)
Megaloblastic anemia stems from deficiencies in?
b12 and folate
What is the term used for anemia as a result of folate deficiency?
Pernicuous anemia
What manifestations are seen in the oral cavity as a result of anemia?
Atrophic glossitis, angular chelitis, and apthous stomatitis
Atrophy of the lingual papillae, fissuring of the oral commissures, and canker sores respectively
What is pancytopenia and why does it lead to hyperplasia of bone marrow?
When there is a reduced cell count in all lines not just RBCs. There is an increase in erythropoietin and this causes marrow to produce precursors for all cell lines and leads to hyperplasia
During digestion B12 binds to what substance in the stomach?
Haptocorrin
After B12 is released from the B12 haptocorrin complex it binds to?
Intrinsic factor
What substance in the plasma does B12 bind to allowing it to be transported to the rest of the body?
Transcobalamin
What is a site for storage of B12?
The liver
What is the most frequent cause of B12 deficiency?
Pernicuous anemia
What is pernicious anemia?
An autoimmune attack on gastric mucosa and the intrinsic factor itself
What will you see in the stomach and intestine in someone who has pernicious anemia?
Intestinal metaplasia, presence of goblet cells in the stomach, and atrophic glands
How does pernicious anemia affect the CNS?
Demyelination of the dorsal and lateral tracts of the spinal cord
What are possible causes of B12 deficiency other than pernicious anemia?
Decreased intake, increased need such as in pregnancy or cancer, gastrectomy so no IF is made, and a fish tapeworm
What is folate used for?
Intermediate in carbon transfer during purine synthesis, specifically thymidine
How does the megaloblastic anemia as a result of folate deficiency differ from B12?
No neurological changes
How is folate deficiency diagnosed?
Decreased levels of folate deficiency in the blood and increased homocysteine level
What is an antagonist of folate that can inhibit absorption?
Methotrexate
What is the most common cause of anemia?
Iron deficiency
What is the etiology or cause of iron deficiency?
Lack of it in diet, celiac disease or gastrectomy, increased requirements, or chronic blood loss
The levels of what substance in plasma correlates with total body iron stores?
Ferritin
What delivers iron to erythroid precursors?
Transferrin
Why regulates iron metabolism?
Hepcidin
What does hepcidin inhibit that reduces iron uptake?
Ferriportin
Hepcidin has the effect of suppressing release of iron from
macrophages
Anemia of chronic disease is most often seen in ?
Hospital settings
Inflammatory mediators such as ____ cause anemia because they stimulate production of?
IL-6, hepcidin, prevents the release of iron from macrophages
What is aplastic anemia?
A syndrome of bone marrow failure due to suppression of multi potent stem cells
What inherited disease can cause aplastic anemia?
Fanconi anemia
What is the pathogenesis of aplastic anemia?
The stem cell attacked by environmental insult and becomes genetically altered leading to attack by T cells or decrease in proliferation
In aplastic anemia only one cell line is initially affected but over time all of them are, this is called?
Pancytopenia
Is the spleen enlarged in aplastic anemia?
No never
