Pathology - S2B2 - Blood 3

Front 1

What is the cause of Megaloblastic Anemia?

Back 1

Vitamin B12 or Folate deficiency

Front 2

Describe why Vitamin B12 and Folate deficiencies cause Megaloblastic Anemia

Back 2

Both are needed for DNA synthesis (Thymidine production) - without DNA Synthesis Erythroid precursor cells cannot replicate

Front 3

Describe the Absorption of Vitamin B12

Back 3

1. B12 is released from its protein-bound form by the action of pepsin and then binds to Salivary Vitamin B12 binding proteins = Cobalophilins or R-binders
2. R-Vitamin B12 complexes are broken down by Pancreatic Proteases in the Duodenum
3. Released B12 then attaches to Intrinsic Factor (from Parietal Cells)
4. IF/B12 attaches to receptor in the Ileum
5. Passed on to Transcobalamin II = plasma transport protein

Front 4

What 3 processes is Vitamin B12 involved in?

Back 4

1. Converts 5-methyl-THF to THF
2. converts Homocysteine to Methionine
3. Methylmalonyl CoA --> Succinyl CoA

**1&2 involve both B12 and Folate

Front 5

What could be 3 general causes of Vitamin B12 deficiency?

Back 5

1. Decreased intake = i.e. vegetarian
2. decreased Absorption
3. Increased requirement

Front 6

What 6 things could cause decreased absorption of Vitamin B12?

Back 6

1. Pernicious Anemia = IF deficiency
2. Gastrectomy = IF deficiency
3. Malabsorption (IBD)
4. Ileal resection
5. Bacterial overgrowth
6. Fish Tapeworm --> Diphyllobothrium latum

Front 7

What 3 things could cause an increased need for Vitamin B12 and result in its deficiency?

Back 7

1. Pregnancy
2. Hyperthyroidism
3. Cancer

Front 8

What is the function of Folate?

Back 8

Involved in 1-carbon transfers in producing Thymidine for DNA synthesis

Front 9

What things are associated with decreased intake of Folic Acid?

Back 9

Alcoholism and infancy

Front 10

What 3 things would cause decreased absorption of Folate?

Back 10

1. Malabsorption (Sprue)
2. Drugs = Anticonvulsants, Oral contraceptives
3. Intestinal disease (Lymphoma)

Front 11

What would cause an increased loss of Folate?

Back 11

Hemodialysis

Front 12

What 4 things would cause an increased requirement for Folate and therefore cause deficiency?

Back 12

1. Pregnancy
2. Infancy
3. Cancer
4. increased Hematopoiesis

Front 13

What drug impairs the use of Folate

Back 13

-Methotrexate = inhibits DHF Reductase-
-5-FU = inhibits Thymidylate Synthase

Front 14

Describe the pathogenesis of Megaloblastic Anemia

Back 14

1. B12 or Folate Deficiency
2. Decreased DNA synthesis
3. Impaired nuclear maturation
4. Megaloblastic anemia

Front 15

Describe how Pernicious Anemia causes Megaloblastic Anemia

Back 15

-Autoimmune disease in which Parietal Cells/IF is absent
-Lack of IF results in lack of absorption of Vitamin B12

Front 16

Pernicious Anemia Antibody mechanism of action
-I
-II
-III

Back 16

I = block B12 binding to IF

II = block B12/IF binding to Ileal receptor

III = against gastric proton pump

Front 17

What features can be seen on Blood Smear in Megaloblastic Anemia? (2)

Back 17

1. Macro-ovalocytes = ↑ MCV

2. Hypersegmented Neutrophils
-have 7-10 lobes instead of 2-4

Front 18

What Lab findings are consistent with Megaloblastic Anemia due to B12 deficiency? (3)

Back 18

1. decreased SERUM B12

2. Increased Methylmalonic Acid

3. Increased serum Homocysteine

Front 19

What lab finding is consistent with Megaloblastic Anemia due to Folate Deficiency?

Back 19

Decreased *Red Cell* Folate


**Serum is not measured

Front 20

Compare the length of time it takes to become deficient in B12 vs. Folate

Back 20

B12 deficiency takes years to become deficient because it is stored in the LIVER

Folate deficiency can arise within months

Front 21

Do Neurological problems occur in patients with B12 or Folate deficiency?

Back 21

B12

Front 22

What are the 3 clinical features of B12 deficiency?

Back 22

1. Megaloblastic anemia
2. Atrophic Glossitis = red & enlarged tongue
3. Neurologic abnormalities = ataxia, impaired proprioception and vibratory sensation

Front 23

Type of anemia associated with Iron Deficiency?

Back 23

Hypochromic Microcytic anemia

Front 24

Which is absorbed more readily, Heme Iron or Non-heme iron?

Back 24

Heme iron

**25% of Heme iron vs. 1-2% of non-heme iron is absorbable

Front 25

What is the physiological storage form of Iron?

What is the transport protein for Iron?

Degraded Ferritin + Lysosomal debris = ?

Back 25

Ferritin

Transferrin

Hemosiderin

Front 26

What is the most important function of Transferrin?

Back 26

to deliver Iron to cells, including Erythroid precursors, which require iron for Hemoglobin synthesis

Front 27

What is the daily requirement of Iron?

Back 27

1 mg absorbed or 10-20mg dietary

Front 28

Globally, what is the most important cause of Iron deficiency?

Back 28

Decreased Dietary Intake

Front 29

In the US, what is the most important cause of Iron Deficiency?

Back 29

Chronic blood loss

Front 30

What would be possible causes of Chronic blood loss and Iron deficiency?

Back 30

1. GI = peptic ulcers, hemorrhagic gastritis, gastric CA, Colon CA,)
2. GYN = menorrhagia, uterine cancer
3. GU = renal, pelvic, or bladder tumors

Front 31

What are the abnormal Lab values in Iron Deficiency Anemia?

Back 31

Decreased
-Serum Iron
-Serum Ferritin
-Transferrin saturation

Increased
-Total Iron Binding capacity (TIBC)
-Transferrin receptor
-Free Erythrocyte Protoporphyrin

Front 32

What are the Blood Smear findings of Iron Deficiency Anemia?

Back 32

1. Hypochromic microcytic anemia

2. Decreased MEAN CELL VOLUME (MCV)

Front 33

What are the clinical features of Iron Deficiency Anemia

Back 33

1. Hypochromic, microcytic anemia
2. Atrophic glossitis
3. Koilonychia = spoon nails with abnormal splitting
4. Plummer-Vinson Syndrome = Esophageal Webs, Glossitis, Iron Deficiency

Front 34

What is Plummer-Vinson Syndrome?

Back 34

1. Esophageal Webs
2. Glossitis
3. Iron Deficiency

**increased risk for developing Esophageal Cancer

Front 35

What is the treatment for Iron Deficiency?

Back 35

1. Iron supplementation

2. Investigation and treatment of the underlying disease

Front 36

Describe the pathogenesis of Anemia of Chronic Disease

Back 36

-

Front 37

Most common cause of anemia among hospitalized patients in the U.S.

Back 37

Anemia of Chronic Disease

Front 38

What are the possible underlying disease causing Anemia of Chronic Disease?

Back 38

1. Chronic microbial infections
2. Chronic Immune Disorders = Rheumatoid arthritis
3. Neoplasms = Hodgkin's and Lung/Breast CAs

Front 39

How do cytokines and inflammatory modulators cause anemia of chronic disease?

Back 39

Lead to decreased Renal EPO secretion

Front 40

What are the 2 ways in which anemia is caused in chronic disease?

Back 40

1. Cytokines cause decreased renal EPO secretion

2. Impaired Iron Utilization -> IL-1 causes increased Lactoferrin, which in turn traps iron in BM macrophages

**Lactoferrin is an antimicrobial protein that has a high affinity for Iron

Front 41

What are the lab findings in Anemia of Chronic Disease?

Back 41

1. Low serum Iron
2. Low Total Iron Binding Capacity (TIBC)
3. High Serum Ferritin

*normal serum transferrin receptor

Front 42

How do you differentiate between Iron deficiency anemia and Anemia of Chronic Disease?

Back 42

Iron deficiency = low serum ferritin and high TIBC

Anemia of Chronic Disease = high serum ferritin and low TIBC

Front 43

What is the treatment for Anemia of Chronic Disease?

Back 43

1. treatment of underlying disorder
2. Recombinant EPO

Front 44

Define Aplastic Anemia

Back 44

Hypocellular Bone Marrow with almost total loss of hematopoietic cells, including Erythroid and Myeloid precursor cells

Front 45

What are 65% of the causes of Aplastic Anemia?

Back 45

Idiopathic
-Stem Cell defect
OR
-autoimmune dysfunction of cytotoxic T cells

Front 46

What chemicals can cause Aplastic Anemia?

Back 46

1. Alkylating agents
2. Benzene
3. Chloramphenicol
4. Insecticides
5. Antimetabolites (5-FU, Methotrexate
6. Arsenicals

Front 47

What viral infections can typically cause Aplastic Anemia?

Back 47

1. Parvovirus B19
2. EBV
3. CMV
4. HIV
5. Herpes VZV
6. HCV

Front 48

T or F: Radiation can cause Aplastic Anemia

Back 48

True

Front 49

In about 50% of cases, what response removes Hematopoietic cells from the BM and causes Aplastic Anemia?

Back 49

T-cell response

Front 50

What is the inherited form of Aplastic Anemia?

Back 50

Fanconi anemia

Front 51

What are the lab findings of Aplastic Anemia?

Back 51

1. Anemia = fatigue
2. Neutropenia = recurrent infections
3. Thrombocytopenia = bleeding and petechiae

Front 52

Describe the pathogenesis of Aplastic Anemia

Back 52

-

Front 53

Hypocellular Bone Marrow in Aplastic Anemia

Back 53

What is this showing?

Front 54

What is the treatment for Aplastic Anemia (2)

Back 54

1. Immunosuppression -> Antithymocyte globulin

2. Bone Marrow Transplantation

Front 55

What is Pure Red Cell Aplasia associated with?

Back 55

Thymoma = tumor of the thymus

Front 56

What is Myelophthisic Anemia?

Back 56

Anemia caused by Bone Marrow replacement, most often by a malignant neoplasm

**can also be due to Marrow Fibrosis

Front 57

How could Chronic Renal Failure lead to anemia?

Back 57

decreased synthesis of EPO

Front 58

What is Polycythemia?

Back 58

increased concentration of RBC's, usually with a corresponding increase in Hb levels

Front 59

What is the cause of Relative Polycythemia?

Back 59

Any kind of dehydration that causes increased concentration of RBC's

Front 60

What is Absolute Polycythemia?

Back 60

An actual increase in the # of RED CELL MASS

Front 61

What is Primary Absolute Polycythemia?

Back 61

Caused by an intrinsic abnormality of Myeloid Stem Cells
-clonal proliferation (polycythemia vera)
-increased responsiveness to EPO due to mutation in the EPO receptor

Front 62

What is Secondary Absolute Polycythemia?

Back 62

Presents with normal Red Cell Progenitors but an increased amount of EPO, which causes proliferation of Erythrocytes

Front 63

What are some Appropriate causes of Secondary Absolute Polycythemia?

Back 63

1. Lung disease
2. Cyanotic heart disease
3. High altitude

Front 64

What are some Inappropriate causes of Secondary Absolute Polycythemia?

Back 64

EPO-secreting tumors

Front 65

Megaloblastic Anemia

Macro-ovalocytes and Hypersegmented Neutrophils

B12 or Folate deficiency

Back 65

What is this picture showing?
How do you know?
What is the cause?

Front 66

1. Iron deficiency

2. Hypochromic microcytic anemia (low MCV)

3. Thalassemias = low Hb / Anemia of Chronic Disease = iron is trapped in BM macrophages

Back 66

1. What deficiency is this due to?
2. What type of anemia is it?
3. What other 2 diseases could cause it?