Pathology of Anemia

Question 1

Anemia

1. Blood Loss - Acute vs. Chronic (examples)

Answer 1

Acute: trauma

Chronic: GI disturbance (ulcer, tumor) or Gynecological disturbance

Question 2

Anemia

1. Decreased RBC Production (4 reasons)

Answer 2

1. Inherited Genetic Defects
   - Fanconi Anemia (defects in stem cells depletion)
   - Thalassemias (defects in erythroblast maturation)
2. Nutritional Deficiencies
   - Vitamin B12/Folate (defective DNA synthesis)
   - Iron deficiency (defective Hb synthesis)
3. Erythropoietin (EPO) Deficiency
   - Renal Failure, Anemia of chronic disease
4. Immune-mediated Injury to Progenitors
   - Aplastic anemia, pure red cell aplasia

Question 3

Other Causes of Anemia via Decreased RBC Production

(4 of them)

Answer 3

1. Inflammation-induced iron sequestration (Anemic of chronic disease)
2. Primary Hematopoietic Neoplasms (Acute Leukemia, Myelodysplasia, Myeloproliferative disorders)
3. Space-occupying Marrow Lesions (Metastatic neoplasms, Granulomatous disease)
4. Infection of RBC progenitors (Parvovirus B19 infection)

Question 4

Anemia

1. Increased RBC Destruction (Inherited - 3 examples)

Answer 4

1. RBC membrane disorders (Hereditary spherocytosis, hereditary elliptocytosis)
2. Enzyme deficiencies (HMP shunt - G6PD and glutathione reductase; Glycolytic Enzymes - pyruvate kinase/hexokinase)
3. Hemoglobin abnormalities (Thalassemia, Hemoglobinopathies, Sickle Cell anemia, Unstable Hb)

Question 5

Anemia

1. Increased RBC Destruction (Acquired - 3 types)

Answer 5

1. Deficiency of PIGA
2. Antibody Mediated

***3. Mechanical Trauma to RBCs

-Microangiopathi Hemolytic Anemia –> Disseminated Intrvascular Coagulation (DIC)

-Chemical Injury –> Lead poisoning (any house before 1978)

Question 6

What other cell is comparable to the size of a RBC?

Answer 6

The nucleus of a lymphocyte

Question 7

What are the 4 things you look for in a PBS?

Answer 7

1. Normochormic (normal amt of Hb; whtie dot ~1/3 of diameter)
2. Minimal Poikilocytosis (most are nice and round in shape)
3. Minimal Anisocytosis (most are pretty much the same size)
4. Nothing weird going on (e.g. no nucleated RBCs, no infectious orgnaisms within RBCs (e.g. malarial organisms), no iron aggregates, no Howell-Jolly bodies, etc.)

Question 8

Answer 8

Anisocytosis

(Variation in size)

Question 9

Answer 9

Anisocytosis

(Variation in size)

Question 10

Answer 10

Poikilocytosis

(Variation in shape)

Question 11

Answer 11

Poikilocytosis

(Variation in shape)

Question 12

Hyper- vs. Hypochromic

Answer 12

Question 13

Answer 13

Hypochromasia (increased central pallor)

Question 14

Polychromasia (RBCs with more than one color)

1. How will a reticulocyte present?

Answer 14

Larger, bluish gray (as it is H&E stained and has RNA still, so stains bluish-gray)

Question 15

Answer 15

Polychromasia

(sign of cellular immaturity)

-Polychromatic RBCs are characterized by their large size and bluish hue due to their RNA content

Question 16

What is Normoblastemia?

What conditions will it be found in?

Answer 16

1. Presence of nucleated RBCs in PBS
2. Hemolytic Anemias

Question 17

Answer 17

Normoblastemia

(Seen in hemolytic anemia)

Question 18

What kind of cell is this, and what disorders can you find it in?

Answer 18

Spherocytes

Hereditary Spherocytosis

Autoimmune Hemolytic Anemia

Question 19

What kind of cell is this, and in what disorders will you find it?

Answer 19

Schistocyte

Microangiopathic Hemolytic Anemia (DIC, TTP, HUS - Hemolytic Uremic Syndrome)

Other Hemolytic Anemias

Question 20

What does a PBS look like in a patient with lead poisoning?

Answer 20

Coarse, basophilic stippling

Question 21

What does this slide show and what causes it?

Answer 21

Punctate Basophilia/Basophilic Stippling

Causes:

-Severe anemia, LEAD POISONING, Severe infection, Drug exposure, Alcoholism

Question 22

Answer 22

Basophilic Stippling

Question 23

What are these and what do they indicate?

Answer 23

Howell-Jolly Bodies (H-J Bodies)

• Purple nuclear remnants
• Larger than basophilic stippling

***Indicate absence of spleen/post-splenectomy or hemolysis

Question 24

Answer 24

Reticulocyte

Question 25

What is a normal vs. abnormal Retic Count?

Answer 25

Question 26

What is hemoglobin composed of?

Answer 26

Hb = heme + globin chains

Question 27

**Defects in Synthesis of Hb** 1. Defects in _Heme Synthesis_ (3)

Answer 27

1. Iron Deficiency 2. Anemia of Chronic Disease 3. Sideroblastic Anemias

Question 28

**Defects in Synthesis of Hb** 1. Defects in Synthesis of Globin Chains (a/B)

Answer 28

alpha and Beta **thalassemias**

Question 29

Answer 29

Microcytic Anemia

Question 30

Answer 30

Microcytic Hemochromic Anemia | (**Iron Deficiency Patient**)

Question 31

What are the 4 common cause of **Macrocytic (MCV \> 100 fL) Anemia**?

Answer 31

1. Vitamin B12/Folate Deficiency 2. Alcohol Use 3. Liver Disease 4. Reticulocytosis

Question 32

What are 2 uncommon causes of Macrocytic Anemia?

Answer 32

Myelodysplastic Syndrome Hypothyroidism

Question 33

**Macrocytic Anemia** 1. Pathogenesis

Answer 33

_Defective DNA Synthesis_ (B12/Folate deficiency) _Increased RBC Membrane_ (From lipid alterations associated with **alcohol use**)

Question 34

**Normocytic Anemia (MCV = 80-100 fL)** 1. Reticulocyte Count \< 3% 2. Reticulocyte Count \> 3%

Answer 34

1. Acute blood loss (\<7 days), Aplastic Anemia, Anemia of Chronic Disease, Renal Disease, Early Iron Deficiency 2. **Intrinsic RBC Defect** --\> Membrane Defects, Abnormal Hb, Defective Enzyme **Extrinsic RBC Defect** --\> Autoimmune hemolytic anemia, PNH, Microangiopathic Hemolytic Anemia

Question 35

What happens if the patient survives an acute blood loss?

Answer 35

- Intravascular shift of water from interstitial fluid compartment - **Hemodilution - low PCV** Reduced oxygen --\> stimulates EPO --\> stimulated erythroid hyperplasia --\> **Reticulocytes appear** in peripheral blood after **5 days**

Question 36

**Acute Blood Loss** 1. Clinical Effects (depends upon...)

Answer 36

- Rate of hemorrhage - Whether bleeding is **external** or **internal** External (e.g. peptic ulcer) --\> may result in _iron deficiency_ Internal (e.g. ruptured AAA) --\> iron is **recaptured**