Flashcards in Ch 20: Hematopoiesis and RBC Deck (60):
Hematopoietic Stem Cell production arises from which dermal layer and moves around from which organs during fetal development to childhood
Yolk Sac->Fetal Liver(3rd Month)->Bone Marrow(4th Month) Primary Site at 26th Week
Hematopoiesis in liver stops at birth
Red Marrow and Yellow Marrow serve which functions?
Red: hematopoietic tissue
White: adipose tissue (capable of reactivating to red marrow to meet demands)
Extramedullary hematopoiesis in an adult usually suggests...
Clonal (malignant) disorder opposed to a reactive process
Red bone marrow consists of which two main divisions?
Cords of stromal and hematopoietic cells
Sinusoids: separate cords and provide path for mature cell release
Main stem cell which all blood cells descend from?
What are the two multipotent cell lines?
Pluripotent hematopoietic stem cells
Lymphoid precursor cell and CFU-GEMM (granulocyte, erythroid, macrophage, megakaryocyte)
5 CFU-GEMM Progenitor Cells and what they become?
CFU-Meg: Megakaryocyte->Platelet production
BFU-E: Proerythroblast--->Orthochromatophilic erythroblast (has nucleus)->Reticulocyte (common test for marrow response to stress)->Erythrocyte
CFU-GM: Neutrophil and Monocyte
What does Stem cell factor, IL-3, Colony Stimulating Factor, Erythropoietin, and Thrombopoietin do?
Promotes survival and proliferation of hematopoietic cells
What increases erythropoietin release (organ and signal)?
Kidney releases EPO in response to hypoxia (EPO prevents apoptosis of precursors)
What is the cellularity (proportion of hematopoietic cells to fat) in the average adult? Do children or adults have more red marrow?
50:50, Children have more red marrow and fat marrow proportion increases as life passes
Hematopoiesis is a highly regulated process from cell synthesis to release in the blood. What cell type increases in bone marrow when a malignant proliferative order is to blame compared to normal reactive hematopoiesis
We get and increase in Blasts when such pathology occurs
How many irons/oxygens can 1 molecule hold?
What state is the iron in?
Heme (protoporphyrin + iron) + globin
4 iron/oxygen per hemoglobin
What is a normal hemoglobin/hematocrit/mean cell volume (MCV)?
Hemoglobin: 14-18g/dl (M); 12-16g/dl (F)
Hematocrit: 40-54% (M); 35-47% (F)
What are the 3 classifications of anemia based on MCV?
What are the 4 pathologic classifications of anemia?
MCV: Normocytic, Macrocytic (big), Microcytic (small)
Pathophys: 1.Acute blood loss 2. Decreased production 3. Ineffective hematopoiesis 4. Increased destruction (intra or extracorpuscular)
A normal response to increased destruction of red cell by the body is an increase in circulating...?
Reticulocytes (normally 0.5-2.5%)
EPO will cause more erythropoiesis in response to hypoxia
Normocytic, normochromic anemia following a motorcycle accident...cause of the anemia?
Acute blood loss followed by fluid resuscitation causes a RBC/unit volume
Most common cause of MICROCYTIC ANEMIA worldwide (and all anemia for that matter)?
Name some ways it can occur
Dietary deficiency; Malabsorption due to pathology of duodenum/jejunum; Chronic blood loss (tumor or lesion?); Pregnancy/lactation; Intravascular hemolysis
What does RDW stand for and imply?
Red cell distribution width: variation in cell sizes due to macro/microcytic anemia (Anisopoikilocytosis: various size and shape)
RBC smaller than WBC nucleus w/ increased central pallor and some thin "pencil cells"? Name that pathology?
What does Prussian blue stain?
This disease shows elevated Ferritin with low iron binding capacity and serum iron. Normocytic/Microcytic cellls
Anemia of Chronic Disease: Due to body trying to sequester iron
This type of anemia may be due to injury to the bone marrow stem cells due to an immune response, chemotherapy or even genetic cause (Fanconi Anemia)
EPO levels will be elevated w/pancytopenia present
Aplastic Anemia: anemia of pluripotential stem cells that leads to bone marrow failure
Need transplant or survival very low
De novo mutation manifests in first 2 years of life; causes Pure Red Cell Aplasia (PRCA): only erythroid precursors suppressed
Which illness can cause an aplastic crisis in those with anemia
Parvovirus B19; can even cause acute self-limited PRCA
Repeated about 10 times in this section, super high yield....don't forget Malaria can also cause some problems too
Decreased production of EPO; normocytic, normochromic, some scalloped cells (Burr cells). Name that Anemia!
Anemia of Renal Disease
Normocytic anemia of bone marrow infiltration
May be accompanied by Leukoerythroblastosis (immature granulocytes and nucleated erythrocytes)
In anemias of B12/folate deficiency, is there heavy precursor proliferation?
YES! However, due to poor maturtity due to lack of factors needed, many are not released to blood
Decreased B12 or folate leads to impairment of ____ synthesis, causing __________ anemia. What can you tell me about the neutrophils?
Antibodies have attacked your parietal cells! What factor are you now missing, what vitamin does it transport, and where is it absorbed? What do we call this anemia?
Intrinsic factor; B12; Ileum; Pernicious anemia
Macrocytic Anemia: One less division due to defective DNA synthesis
Microcytic Anemia: One more division to cover up lack of hemoglobin
No Question! Just fun facts from Dr Sattar!
Test measures B12 absorption using radiotracers
What develops most rapidly, folate or B12 deficiency?
Folate (months); B12 (years)
Known as a congenital defect in globin synthesis. Generally result in microcytic anemia of some sort...
Most common around Mediterranean and areas of Malaria endemic
Name those globin chains!
HbA; HbA2; HbF; HbH; HbBarts
H: b4 (alpha thalassemia)
Barts: gamma4 (babies w/alpha thalassemia)
Cooley anemia caused by point mutation?
Which hemoglobin type upregulates to cover the loss?
What is a side effect of this upregulation?
HbF (fetal) is upregulated to cover the loss
Since HbF holds the oxygen so well, the kidneys perceive hypoxia->increase EPO->extramedullary hematopoiesis->hepatosplenomegaly and iron overload (chelation therapy needed)
What do we call precipitates of HbH and HbBarts and alpha4 tetramers?
Name 2 Thalassemia disorders in which the degree of microcytosis is worse than the actual anemia (which is usually very mild)
What chromosome is the alpha globin on and what is the total number of copies present?
What chromosome are all other globins on and how many copies are there?
A: 16, 4 copies
All others: 11, 2 copies
Who is most likely to pass an A-Thalassemia trait to an offspring that will result in severe anemia and Hemoglobin H disease? (Mediterranean, African, or Southeast Asian)
Southeast Asian: They tend to carry the mutation of 2 alpha globin genes on the same chromosome, allowing for a complete alpha knockout on one gene when given to progeny
How many mutations in Alpha globin gene do you need to result in Hydrops fetalis (incompatible with life)? What about Hemoglobin H disease?
How many mutations does a SILENT carrier have?
Hemoglobin H: 3 (or 4 but they don't survive)
Silent: 1 (many people don't even know they have it, no effects)
Where does extravascular hemolysis occur? What about intravascular? Name the two most common side effects.
Extravascular: monocyte/macrophage system
Intravascular: destroyed in circulation
Increased unconjugated bilirubin (jaundice, gallstones, hemoglobinemia/uria w/high serum iron) and splenomegaly
Ok so thats more than 2, but if you understand that all this is because of free hemoglobin being released which needs to get taken care of, your golden
Deficiency of spectrin (cytoskeleton component), normocytic anemia, hyperchromatic cells lack central pallor
Predominant extra or intravascular?
Hereditary spherocytosis (inherited dominant (recessive rare))
Extravascular->spleen noms on the membrane
Managed with splenectomy since it keeps stealing RBC membrane
Splenectomy and Autosplenectomy predisposes you to what?
Susceptible to encapsulated organisms, most commonly Streptococcus
Elliptical cells with parallel sides due to defects in assembly of cytoskeleton
Predominant extra or intravascular?
Hereditary Elliptocytosis, anemia usually much more mild than spherocytosis
Extravascular->spleen noms on the membrane
Defect within lipid bilayer, common in chronic liver disease due to high free cholesterol?
Describe the cell.
Acanthocytosis: Spur Cells (lack central pallor with spikes on surface)
I've been eating flava beans and now I'm anemic, what enzyme am I missing?
Name the cell morphology caused by the spleen
Im sensitive to oxidative stress, now my Fe2+ is being converted to Fe3+ (methemoglobin)->Heinz bodies->hemolysis
Cell Morphology: Bite cells (looks like someone bite off the corner)
Point mutation in b-globin (Valine for Glutamic acid)? RBC change shape upon deoxygenation
Bodies of nuclear remnants are called?
Most common sequelae?
Will a baby show signs?
What will happen to my spleen/kidneys?
Most common in _______ due to protection from _______
Sickle Cell Disease
NO! HbF will protect them for a while
Autosplenectomy; Renal necrosis
African Americans; Malaria (in heterozygotes (cells don't normally sickle))
Which is more severe? HbS or HbC
Which hemoglobinopathy is similar to a thalassemia (microcytic anemia w/hypochromic cells)?
HbE: unstable mRNA splicing causes decreased B-globin and thalassemia traits
Increased oxygen affinity in other hemoglobinopathies causes EPO to?
Decreased oxygen affinity will cause?
EPO will increase->compensates->asymptomatic
EPO will decrease due to O2 unloading->anemic state and cyanotic appearence
Warm antibodies are predominantly Ig_?
Cold are Ig_?
What is the class of hemolytic anemia these fall under
Autoimmune hemolytic anemia (AIHA)
What test do we use for detecting autoimmune hemolytic anemia
Direct Coombs Test
Name the three mechanisms that warm antibodies use
How do we treat?
Hapten mechanism: drug binds erythrocyte which causes antibodies to bind the drug there
Immune complex: drug binds circulating antibodies which creates immune complexes
Autoantibody: drug causes antibody formation that cross reacts with RBC (can occur even in absence of drug)
Rx: suppress immune system: corticosteroids or other immunosuppresive agents (occastional splenectomy if severe)
How do cold antibodies cause damage?
Which infection can cause cold agglutinins?
IgM can either AGGLUTINATE or bind COMPLEMENT to RBCs in cooler peripheral circulation which are then undergo extravascular hemolysis in the liver
Complement may also cause MAC intravascular hemolysis
Epstein Barr Virus can cause cold agglutination antibody formation
Cold induced, IgG mediated hemolysis disease that doesn't involve agglutination? What does it normal follow and how do we treat?
Paroxysmal Cold Hemoglobinuria->Only IgG warm they attract complement and are intravascularly hemolysed
Follows virus, Rx: transfusions and cold avoidance only
What happens when you give grossly incompatible blood to a patient w/preformed antibodies?
What about if they have minor red cell antigens?
Immediate hemolytic transfusion reaction (can easily result in death)
Delayed hemolytic transfusion reaction (less severe)
Give an example of a hemolytic disease of the newborn. How do you prevent it
Mom Rh-, baby Rh+. Severe anemia in baby if mom previously exposed to Rh+ antigen via pregnancy or transfusions. Hydrops fetalis possible. Prevent with Rh immune globulin.
ABO mom to fetus may also occur but usually very mild
Name two microangiopathic hemolytic anemias.
What do we call the fragmented erythrocyte they create?
Disseminated intravascular coagulation
Thrombotic throbocytopenia purpura
Lack of PIG-A gene leads to loss of GPI linked membrane proteins: Decay accelerating factor and membrane inhibitor of reactive lysis. Name that disease and 3 tests we use to diagnose. What syndrome does it commonly cause?
Paroxysmal Nocturnal Hemoglobinuria: at night time, decreased P02 causes complement to activate and without these bound proteins, are RBC are bound by complement and lyse
3 Tests: Sucrose Hemolysis Test, Ham Test (acidify serum), and Flow cytometry (for GPI anchored proteins)
Syndrome: Budd Chiari syndrome (hepatic vein thrombosis)
Mild hemolytic anemia due to excess transit time in a certain organ. Name the organ and disease.
Compensatory hyperplasia of all bone marrow cell lines
What kind of hemolysis do burns cause?
What microorganisms have intraerythrocytic life cycles and cause hemolysis?
Burns: intravascular hemolysis with schistocytes
Organisms: Plasmodium and Babesiosis