Pathology - S2B2 - Blood 1

Front 1

What does the Pluripotent Bone Marrow Stem Cell give rise to?

Back 1

1. Trilineage Myeloid Stem Cell

2. Lymphoid Stem Cell

Front 2

What committed stem cells does the Myeloid Stem Cell give rise to?

Back 2

1. Eosinophil Stem cell
2. Granulocyte/Macrophage SC
3. Erythroid/Megakaryocyte SC

Front 3

What does the Lymphoid Stem Cell give rise to?

Back 3

1. Pro-B cells -> Plasma cells
2. Pro-NK cells
3. Pro-T cells

Front 4

What is the difference between the cells derived from the Myeloid and Lymphoid Stem cells?

Back 4

-Cell derived from the Myeloid cell line differentiate in the Bone Marrow

-Cells from the Lymphoid cell line migrate to Lymphoid organs: Thymus, Lymph nodes, Spleen, MALT

Front 5

Growth Factors that stimulate Pluripotent Stem Cell to differentiate into Myeloid or Lymphoid Stem Cells

Back 5

1. SCF
2. IL-6
3. Flt3-ligand

Front 6

Growth Factor that stimulates differentiation down the Eosinophil Cell line

Back 6

IL-5

Front 7

Growth Factors that stimulate differentiation down the Lymphoid cell line

Back 7

1. SCF
2. Flt3-ligand
3. IL-7

Front 8

Growth Factors that stimulate down the Erythroid/Megakaryocyte Cell line

Back 8

TPO and IL-11

Front 9

GF that stimulates the Erythroid cell line

Back 9

EPO

Front 10

GF that stimulates differentiation down the Megakaryocyte/Platelet cell line

Back 10

TPO = Thrombopoietin

Front 11

GF that stimulates differentiation down the Monocyte/Macrophage cell line

Back 11

M-CSF

Front 12

GF that stimulates differentiation down the Neutrophil cell line

Back 12

G-CSF

Front 13

Prenatal Hematopoiesis:
-Hematopoiesis begins in the __1__ at the end of the 3rd week of gestation
-By the end of the 1st trimester, the __2__ develops into the most prominent source of hematopoiesis
-Hematopoiesis begins to occur in the __3__ at around the 4th month of development

Back 13

1. Yolk Sac and Mesoderm (Intraembryonic Aorta/gonad/mesonephros region)
2. Liver (3 mo - birth)
3. Bone marrow (4 mo onwards)

Front 14

Where does hematopoiesis take place post-natally?

Back 14

Bone Marrow

Front 15

Give 3 reasons as to why Extramedullary Hematopoiesis (outside the BM) might take place

Back 15

1. Insufficient bone marrow reserve
2. Bone Marrow damage
3. Myeloid neoplasms

Front 16

List 4 sites where Extramedullary Hematopoiesis may occur

Back 16

1. Liver (most prominent)
2. Spleen
3. Lymph nodes
4. Soft tissue

Front 17

What 3 things does Bone Marrow consist of?

Back 17

Sinusoids

Hematopoietic Cells

Fat

Front 18

What are the normal adult ratios of:
1. Hematopoietic cell:Fat
2. Myeloid:Erythroid

Back 18

1. 1:1

2. 3:1

Front 19

As we grow older, where is Hematopoiesis usually restricted to?

Back 19

Flat bones and the ends of Long bones
-Vertebrae
-Ribs
-Sternum
-Skull
-Pelvis
-Proximal epiphyseal portions of the humerus and femur

Front 20

Fat = empty spaces

Back 20

Identify:
Fat
Hematopoietic cells

Front 21

Label the following Granulocytic Cells through their Maturation

Back 21

-

Front 22

Label the following cells

Back 22

-Pronormoblast = earliest recognizable erythroid
-Polychromatophilic = has basophilic cytoplasm with pink
-Orthochromatic = cytoplasm is entirely grayish-pink, nucleus is small and pyknotic

Front 23

What is the 1st anucleated state of Erythroids?

Back 23

Reticulocytes

Front 24

Term defined as the ratio of RBC to Serum expressed in percentages

Back 24

Hematocrit

Front 25

Term defined as the average calculated volume of a single RBC

Back 25

Mean Cell Volume (MCV)

Front 26

Term defined as the average content of Hemoglobin in each RBC

Back 26

Mean Cell Hemoglobin

Front 27

Term defined as the average concentration of Hemoglobin in a given volume of packed RBC's

Back 27

Mean Cell Hemoglobin Concentration

Front 28

Immature erythrocytes with residual RNA

Back 28

Reticulocytes

Front 29

What is the term to describe Reticulocytes seen on a blood smear?

Back 29

Polychromasia = cell that is not perfectly pink, but still has a little gray in it

Front 30

Reticulocytes are bigger and grayer

Embedded RNA

Back 30

Point out a Reticulocyte on the blood smear

What is this Methylene Blue stain staining in the bottom right pic?

Front 31

What does the Reticulocyte Count reflect?

Back 31

Bone Marrow Erythropoiesis

Front 32

What is the normal range for Reticulocytes in the peripheral blood?

Back 32

0.5 - 1.5%

**if more, could be indicative of anemia

Front 33

Define Anemia

Back 33

Decrease in the RBC mass and the Hemoglobin content in the blood

Front 34

What 3 lab parameters may be decreased in Anemia?

Back 34

1. RBC count
2. Hemoglobin
3. Hematocrit

Front 35

List 6 signs and symptoms common to all forms of Anemia

Back 35

1. Pallor = pale skin & mucosa
2. Easy fatigability
3. Dyspnea upon exertion
4. Koilonychia
5. Tachycardia, Angina
6. Dizziness

Front 36

Koilonychia

Severe, prolonged Anemia

Back 36

What is the flattening of nails with spoon-shaped concavity called?

What is the cause?

Front 37

What are the 3 Pathophysiologic classifications of Anemia?

Back 37

1. Blood loss
2. Increased rate of destruction (hemolytic anemias)
3. Impaired Red Cell production

Front 38

List the 3 Morphologic Classifications of Anemia based on Cell Size (MCV)

Back 38

1. Macrocytic
2. Normocytic
3. Microcytic

Front 39

List the 2 Morphologic Classifications of Anemia based on Hemoglobin Concentration (MCHC)

Back 39

1. Normochromic

2. Hypochromic (increased central pallor)

Front 40

What would be a cause of Macrocytic Anemia (increased RBC size)?

Back 40

Megaloblastic Anemia due to Vitamin B12 or Folate deficiency

Front 41

What could be 3 causes of Microcytic, Hypochromic anemia? (small RBC size, low Hb concentration)

Back 41

1. Iron Deficiency
2. Thalassemia
3. Anemia of Chronic Disease

Front 42

Term for variation in RBC size

Back 42

Anisocytosis (reflected in the RDW)

*the bigger the Red Cell Distribution Width (RDW) = the greater the Anisocytosis

Front 43

Term for the variation in RBC shape

Back 43

Poikilocytosis

Front 44

What is the type of Anemia with Acute Blood Loss?

Back 44

Normochromic, normocytic anemia

Front 45

What may Acute Blood Loss result in?

Why is the Hematocrit decreased if the patient survives?

When does Reticulocytosis peak?

Back 45

Decreased blood volume resulting in Shock and possible death

Hemodilution caused by a shift of water from the interstitium to maintain blood volume (but RBC % decreases = low Hematocrit)

7-10 days after acute event

Front 46

What type of Anemia is present initially with Chronic Blood Loss? What type ensues later?

Back 46

Normochromic, normocytic anemia

Iron deficiency = Microcytic, Hypochromic Anemia

Front 47

At what sites is Chronic Blood Loss common?

Back 47

1. GI -> ulcer in stomach, colon cancer
2. GU -> bladder stones, kidney stones
3. Menstrual bleeding

Front 48

Give an example of Chronic Blood Loss that may NOT result in Iron Deficiency anemia

Back 48

Internal blood loss -> pulmonary hemorrhage that gets resolved and the iron is taken up by macrophages in the blood

**External blood loss results in Hypochromic, Microcytic anemia

Front 49

What are the 3 main features common to all forms of Hemolytic Anemias?

Back 49

1. Premature RBC destruction (normal lifespan = 120 days)
2. Increased Hb catabolism
3. Increased BM erythropoiesis and increased Erythropoietin = Reticulocytosis

Front 50

What are the 2 classifications of Hemolytic anemias based on site?

Back 50

Intravascular

Extravascular

Front 51

What are the 2 classifications of Hemolytic anemias based on Pathogenetic mechanism?

Back 51

Intrinsic (Intracorpuscular) abnormality

Extrinsic (Extracorpuscular) abnormality

Front 52

List 8 features of Intravascular Hemolysis

Back 52

1. Hemoglobinemia = free Hb conc. in plasma increases
2. Decreased serum Haptoglobin = Hb released from RBC's binds to Haptoglobin
3. Hemoglobinuria = appears after the haptoglobin binding capacity has been saturated
4. Hemosiderinuria
5. Increased Bilirubin leading to Jaundice
6. Increased Fecal Urobilin
7. Increased Serum Lactate Dehydrogenase
8. Methemalbuminemia = heme combining with Albumin

Front 53

What is the unique feature of Extravascular Hemolysis?

Back 53

Splenomegaly = damaged RBC's are sequestered in the Spleen and phagocytized by Splenic Macrophages

Front 54

List 5 features of Extravascular Hemolysis

Back 54

1. Jaundice and Pigment gallstones
2. increased Fecal Urobilin
3. Decreased serum Haptoglobin
4. Increased serum LDH
5. Splenomegaly

Front 55

What are the Intrinsic Abnormalities causing Hemolytic Anemias?

Back 55

Hereditary Membrane disorders, enzyme deficiencies, or hemoglobin synthesis disorders
OR
Acquired membrane defects

Front 56

What is an example an Acquired Intrinsic Abnormality causing Hemolytic Anemia?

Back 56

Paroxysmal Nocturnal Hemoglobinuria

Front 57

What in general causes Extrinsic Hemolytic Anemias? (4)

Back 57

1. Anti-body mediated
2. Mechanical trauma (DIC, HUS, prosthetic cardiac valves)
3. Infections (malaria)
4. Chemicals (lead)

Front 58

Autosomal Dominant disorder that is due to a defect invloving Spectrin in the RBC membrane, which causes a decrease in the RBC surface membrane

Back 58

Hereditary Spherocytosis

Front 59

Explain the Pathogenesis of Hereditary Spherocytosis

Back 59

1. decreased membrane stability
2. loss of membrane
3. Spherocytes
4. Destruction in the spleen b/c spherocytes are not flexible

Front 60

Mutations in these 4 skeletal membrane proteins can cause Hereditary Spherocytosis

Back 60

1. Ankyrin
2. Band 3
3. Spectrin (most common)
4. Band 4.2

Front 61

List 5 pathologic findings of Hereditary Spherocytosis

Back 61

1. Spherocytes
2. Increased Osmotic Fragility = is not biconcave so can't expand
3. Splenomegaly (red pulp congestion)
4. Pigment gallstones = heme catabolism -> increased bilirubin
5. Increased MCHC = jam-packed with Hb

Front 62

Hereditary spherocytosis
-uniformly red
-lack central pallor

**Autoimmue Hemolytic Anemias also cause Spherocytes

Back 62

What disorder is exemplified here? How do you know?

Front 63

What are the 3 clinical features of Hereditary Spherocytosis?

Back 63

1. Anemia = due to lysis of Spherocytes
2. Splenomegaly = spherocytes are sequestered and destroyted
3. Jaundice and pigment gallstones = RBC lysis -> Hb catabolism -> heme -> biliverdin -> unconjugated bilirubin -> Jaundice or Pigment Gallstones

Front 64

What is Hereditary Spherocytosis at an increased risk of?

Back 64

Aplastic crisis due to Parvovirus B19 infection

Front 65

What is the treatment for Hereditary Spherocytosis?

Back 65

Splenectomy
-splenectomy cures the anemia but does not abolish the defect
-Spherocytes are still present in blood but aren't lysed due to spleen removal

Front 66

Explain how G6PD deficiency causes hemolytic anemia

Back 66

1. G6PD produces NADPH
2. NADPH is needed to make Reduced Glutathione
3. Reduced Glutathione reduces Oxidative stresses to RBC's

**Deficiency causes Oxidative stress leading to Hemolysis of RBC's

Front 67

How is G6PD deficiency inherited?

Back 67

X-linked = predominantly MALES affected

Front 68

What are the 2 G6PD deficiency variants?

Back 68

1. African = 10-60% activity

2. Mediterranean = <10% activity

**due to defective protein folding = decreased half-life and activity

Front 69

What does the Blood Smear of G6PD deficiency appear as?

Back 69

Heinz bodies = clumps of oxidized hemoglobin within RBC

Bite cells = Heinz bodies "eaten" by splenic macrophages

**Heinz bodies are visualized with Methylene Blue and Crystal Violet stains

Front 70

What pathway is G6PD involved in?

Back 70

Hexose-Monophosphate Shunt pathway

Front 71

What are the clinical features of G6PD deficiency?

Back 71

Hemolysis (episodic hemolytic anemia)
-Hemoglobinemia
-Hemoglobinuria

Front 72

What can precipitate Oxidative Stress in G6PD deficiency?

Back 72

1. Drugs
-Primaquine
-Anti-malarials
-Anti-TB's
-Sulfonamides
2. Infections
3. Fava beans (Mediterranean)

Front 73

What does G6PD deficiency protect against?

Back 73

Falciparum malaria

Front 74

A 7-year-old girl is referred to your hematology clinic after several abnormal blood tests, which include increased Mean Corpuscular Hemoglobin Concentration and an increased RBC osmotic fragility. You discover that one of the child's parents suffers from a genetic blood disorder.

Back 74

Hereditary Spherocytosis
-Autosomal dominant disorder in RBC membrane protein
-Spherocytes -> Hemolytic Anemia

Front 75

Heinz bodies = clumps of oxidized Hb within the RBC

G6PD deficiency

Back 75

What are these called?
What disease?

Front 76

Left = bite cells
Right = Heinz bodies

G6PD deficiency

Back 76

What is on the left and right?

What disease?

Front 77

A 35-year old AFRICAN-AMERICAN man comes to your office after noticing that his urine has become tea-colored. He tells you that he has just returned from a trip to Kenya where he had taken PRIMAQUINE to guard against contracting malaria. Upon finding HEINZ BODIES on his peripheral blood smear, you suspect that his dark urine will likely resolve on its own shortly.

Back 77

G6PD deficiency