Ch 20: Hematopoiesis and RBC

Question 1

Hematopoietic Stem Cell production arises from which dermal layer and moves around from which organs during fetal development to childhood

Answer 1

Mesoderm
Yolk Sac->Fetal Liver(3rd Month)->Bone Marrow(4th Month) Primary Site at 26th Week
Hematopoiesis in liver stops at birth

Question 2

Red Marrow and Yellow Marrow serve which functions?

Answer 2

Red: hematopoietic tissue
White: adipose tissue (capable of reactivating to red marrow to meet demands)

Question 3

Extramedullary hematopoiesis in an adult usually suggests…

Answer 3

Clonal (malignant) disorder opposed to a reactive process

Question 4

Red bone marrow consists of which two main divisions?

Answer 4

Cords of stromal and hematopoietic cells

Sinusoids: separate cords and provide path for mature cell release

Question 5

Main stem cell which all blood cells descend from?

What are the two multipotent cell lines?

Answer 5

Pluripotent hematopoietic stem cells

Lymphoid precursor cell and CFU-GEMM (granulocyte, erythroid, macrophage, megakaryocyte)

Question 6

5 CFU-GEMM Progenitor Cells and what they become?

Answer 6

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
CFU-EO: Eosinophil
CFU-Ba: Basophil

Question 7

What does Stem cell factor, IL-3, Colony Stimulating Factor, Erythropoietin, and Thrombopoietin do?

Answer 7

Promotes survival and proliferation of hematopoietic cells

Question 8

What increases erythropoietin release (organ and signal)?

Answer 8

Kidney releases EPO in response to hypoxia (EPO prevents apoptosis of precursors)

Question 9

What is the cellularity (proportion of hematopoietic cells to fat) in the average adult? Do children or adults have more red marrow?

Answer 9

50:50, Children have more red marrow and fat marrow proportion increases as life passes

Question 10

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

Answer 10

We get and increase in Blasts when such pathology occurs

Question 11

Hemoglobin=_________+__________
How many irons/oxygens can 1 molecule hold?
What state is the iron in?

Answer 11

Heme (protoporphyrin + iron) + globin
4 iron/oxygen per hemoglobin
Fe2+

Question 12

Formulas!
Hematocrit=
What is a normal hemoglobin/hematocrit/mean cell volume (MCV)?

Answer 12

Hematocrit=MCVxRBC
Hemoglobin: 14-18g/dl (M); 12-16g/dl (F)
Hematocrit: 40-54% (M); 35-47% (F)
MCV: 82-100um^3

Question 13

What are the 3 classifications of anemia based on MCV?

What are the 4 pathologic classifications of anemia?

Answer 13

MCV: Normocytic, Macrocytic (big), Microcytic (small)
Pathophys: 1.Acute blood loss 2. Decreased production 3. Ineffective hematopoiesis 4. Increased destruction (intra or extracorpuscular)

Question 14

A normal response to increased destruction of red cell by the body is an increase in circulating…?

Answer 14

Reticulocytes (normally 0.5-2.5%)

EPO will cause more erythropoiesis in response to hypoxia

Question 15

Normocytic, normochromic anemia following a motorcycle accident…cause of the anemia?

Answer 15

Acute blood loss followed by fluid resuscitation causes a RBC/unit volume

Question 16

Most common cause of MICROCYTIC ANEMIA worldwide (and all anemia for that matter)?
Name some ways it can occur

Answer 16

Iron-Deficiency
Dietary deficiency; Malabsorption due to pathology of duodenum/jejunum; Chronic blood loss (tumor or lesion?); Pregnancy/lactation; Intravascular hemolysis

Question 17

What does RDW stand for and imply?

Answer 17

Red cell distribution width: variation in cell sizes due to macro/microcytic anemia (Anisopoikilocytosis: various size and shape)

Question 18

RBC smaller than WBC nucleus w/ increased central pallor and some thin “pencil cells”? Name that pathology?

Answer 18

Iron-deficient anemia

Question 19

What does Prussian blue stain?

Answer 19

Iron

Question 20

This disease shows elevated Ferritin with low iron binding capacity and serum iron. Normocytic/Microcytic cellls

Answer 20

Anemia of Chronic Disease: Due to body trying to sequester iron

Question 21

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

Answer 21

Aplastic Anemia: anemia of pluripotential stem cells that leads to bone marrow failure
Hypocellular marrow
Need transplant or survival very low

Question 22

Diamond-Blackfan syndrome

Answer 22

De novo mutation manifests in first 2 years of life; causes Pure Red Cell Aplasia (PRCA): only erythroid precursors suppressed

Question 23

Which illness can cause an aplastic crisis in those with anemia

Answer 23

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

Question 24

Decreased production of EPO; normocytic, normochromic, some scalloped cells (Burr cells). Name that Anemia!

Answer 24

Anemia of Renal Disease

Question 25

Normocytic anemia of bone marrow infiltration

Answer 25

Myelophthistic Anemia | May be accompanied by Leukoerythroblastosis (immature granulocytes and nucleated erythrocytes)

Question 26

In anemias of B12/folate deficiency, is there heavy precursor proliferation?

Answer 26

YES! However, due to poor maturtity due to lack of factors needed, many are not released to blood

Question 27

Decreased B12 or folate leads to impairment of ____ synthesis, causing __________ anemia. What can you tell me about the neutrophils?

Answer 27

DNA; Megaloblastic | Neutrophils: hypersegmentation

Question 28

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?

Answer 28

Intrinsic factor; B12; Ileum; Pernicious anemia

Question 29

Macrocytic Anemia: One less division due to defective DNA synthesis Microcytic Anemia: One more division to cover up lack of hemoglobin

Answer 29

No Question! Just fun facts from Dr Sattar!

Question 30

Test measures B12 absorption using radiotracers

Answer 30

Schilling Test

Question 31

What develops most rapidly, folate or B12 deficiency?

Answer 31

Folate (months); B12 (years)

Question 32

Known as a congenital defect in globin synthesis. Generally result in microcytic anemia of some sort...

Answer 32

Thalassemia | Most common around Mediterranean and areas of Malaria endemic

Question 33

Name those globin chains! | HbA; HbA2; HbF; HbH; HbBarts

Answer 33

``` A: a2b2 A2: a2delta2 F: a2gamma2 H: b4 (alpha thalassemia) Barts: gamma4 (babies w/alpha thalassemia) ```

Question 34

Cooley anemia caused by point mutation? Which hemoglobin type upregulates to cover the loss? What is a side effect of this upregulation?

Answer 34

homozygous B-thalassemia 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)

Question 35

What do we call precipitates of HbH and HbBarts and alpha4 tetramers?

Answer 35

Heinz Bodies

Question 36

Name 2 Thalassemia disorders in which the degree of microcytosis is worse than the actual anemia (which is usually very mild)

Answer 36

Heterozygous B-thalassemia | A-Thalassemia Trait

Question 37

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?

Answer 37

A: 16, 4 copies | All others: 11, 2 copies

Question 38

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)

Answer 38

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

Question 39

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?

Answer 39

Hydrops fetalis/Barts:4 Hemoglobin H: 3 (or 4 but they don't survive) Silent: 1 (many people don't even know they have it, no effects)

Question 40

Where does extravascular hemolysis occur? What about intravascular? Name the two most common side effects.

Answer 40

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

Question 41

Deficiency of spectrin (cytoskeleton component), normocytic anemia, hyperchromatic cells lack central pallor Predominant extra or intravascular?

Answer 41

Hereditary spherocytosis (inherited dominant (recessive rare)) Extravascular->spleen noms on the membrane Managed with splenectomy since it keeps stealing RBC membrane

Question 42

Splenectomy and Autosplenectomy predisposes you to what?

Answer 42

Susceptible to encapsulated organisms, most commonly Streptococcus

Question 43

Elliptical cells with parallel sides due to defects in assembly of cytoskeleton Predominant extra or intravascular?

Answer 43

Hereditary Elliptocytosis, anemia usually much more mild than spherocytosis Extravascular->spleen noms on the membrane

Question 44

Defect within lipid bilayer, common in chronic liver disease due to high free cholesterol? Describe the cell.

Answer 44

Acanthocytosis: Spur Cells (lack central pallor with spikes on surface)

Question 45

I've been eating flava beans and now I'm anemic, what enzyme am I missing? Name the cell morphology caused by the spleen

Answer 45

G6PD: x-linked 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)

Question 46

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 _______

Answer 46

``` Sickle Cell Disease Howell-Jolly bodies Vaso-occlusive disease NO! HbF will protect them for a while Autosplenectomy; Renal necrosis African Americans; Malaria (in heterozygotes (cells don't normally sickle)) ```

Question 47

Which is more severe? HbS or HbC | Which hemoglobinopathy is similar to a thalassemia (microcytic anemia w/hypochromic cells)?

Answer 47

HbS | HbE: unstable mRNA splicing causes decreased B-globin and thalassemia traits

Question 48

Increased oxygen affinity in other hemoglobinopathies causes EPO to? Decreased oxygen affinity will cause?

Answer 48

EPO will increase->compensates->asymptomatic | EPO will decrease due to O2 unloading->anemic state and cyanotic appearence

Question 49

``` Warm antibodies are predominantly Ig_? Cold are Ig_? What is the class of hemolytic anemia these fall under ```

Answer 49

Warm IgG Cold IgM Autoimmune hemolytic anemia (AIHA)

Question 50

What test do we use for detecting autoimmune hemolytic anemia

Answer 50

Direct Coombs Test

Question 51

Name the three mechanisms that warm antibodies use How do we treat?

Answer 51

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)

Question 52

How do cold antibodies cause damage? | Which infection can cause cold agglutinins?

Answer 52

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

Question 53

Cold induced, IgG mediated hemolysis disease that doesn't involve agglutination? What does it normal follow and how do we treat?

Answer 53

Paroxysmal Cold Hemoglobinuria->Only IgG warm they attract complement and are intravascularly hemolysed Follows virus, Rx: transfusions and cold avoidance only

Question 54

What happens when you give grossly incompatible blood to a patient w/preformed antibodies? What about if they have minor red cell antigens?

Answer 54

Immediate hemolytic transfusion reaction (can easily result in death) Delayed hemolytic transfusion reaction (less severe)

Question 55

Give an example of a hemolytic disease of the newborn. How do you prevent it

Answer 55

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

Question 56

Name two microangiopathic hemolytic anemias. | What do we call the fragmented erythrocyte they create?

Answer 56

Disseminated intravascular coagulation Thrombotic throbocytopenia purpura Schistocyte

Question 57

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?

Answer 57

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)

Question 58

Mild hemolytic anemia due to excess transit time in a certain organ. Name the organ and disease.

Answer 58

Spleen, Hypersplenism Compensatory hyperplasia of all bone marrow cell lines

Question 59

What kind of hemolysis do burns cause? | What microorganisms have intraerythrocytic life cycles and cause hemolysis?

Answer 59

Burns: intravascular hemolysis with schistocytes Organisms: Plasmodium and Babesiosis

Question 60

Polycythemia of Hcts greater than 50% cause a large increase in blood viscosity. Name the two absolute polycythemia and whether they are EPO dependent.

Answer 60

Primary polycythemia/polycythemia vera: EPO independent Secondary polycythemia: EPO dependent (develops in conditions of perceived hypoxia or may be ectopically produced by a neoplasms (renal/hepatic))