Wake Macrocytic Anemia

Front 1

Reticulocytes

Back 1

- Occurs after extrusion of nucleus from orthochromic normoblast
- Remains in marrow for approx 3 days
- Released into circulation – remodeled (in the liver) with loss of water and membrane
- Normal retics are macrocytic (100-110 fL)

Front 2

What stain do you used on peripheral blood smear to show Reticulocytes?

Back 2

Supravital stain will show ribosomal RMA (residual reticulin) as blue

Front 3

Alcohol and RBCs

Back 3

Mechanism unknown
Acetaldehyde
- can induce membrane changes
- Interferes with cellular division (At bone marrow level interferes with DNA synthesis)

Front 4

Liver Disease and RBCs

Back 4

- Mechanism of macrocytosis unclear
- May be caused by increased lipid (or cholesterol) deposition on red cell membranes
- Target Cells

Front 5

Thyroid Disease and RBCs

Back 5

- Mechanism of macrocytosis unknown
- Autoimmune thyroiditis associated with anti-parietal cell antibodies

Front 6

Spurious Macrocytosis

Back 6

- Artifacts that can occur to normal sized RBCs
- Clumps of RBCs counted as single cells by automated cell counters

Front 7

Myelodysplastic Syndromes

Back 7

- : A group of diseases in which the bone marrow does not make enough healthy blood cells. Also called preleukemia and smoldering leukemia.
- abnormal RBC populationg

Front 8

Histology in Myelodysplastic Syndromes

Back 8

- Hypolobulated or hypogranular neutrophils
- Large and/or abnormally granulated platelets
- Monocytosis
- Occasional blast forms

Front 9

Dx of Myelodysplastic Syndromes

Back 9

Dx on bone marrow morphology…consider the elderly 60+

Front 10

Megaloblastic anemia

Back 10

anemia, often pancytopenia, with macrocytic red blood cells and hypersegmented neutrophils due to an impairment in DNA synthesis

Front 11

What happens on the cellular level of a megablast?

Back 11

- Inadequate conversion of deoxyuridylate to thymidylate
- Slows DNA synthesis
- Delayed nuclear maturation
- Nuclear/cytoplasmic dyssynchrony (ie, immature nucleus/mature cytoplasm)

Front 12

Megaloblastic Anemias
Most common causes

Back 12

B12 (cobalamin) and folate deficiency

Front 13

Characterization of Megaloblastic Anemia

Back 13

defect in DNA synthesis resulting in unbalanced cell growth and impaired division

Front 14

Sources of B12

Back 14

- Animal Products (fish, eggs, poultry)
- Fortified foods (breakfast cereals)

Front 15

Sources of Folate

Back 15

- Leafy greens
- Fortified foods (cereals)

Front 16

Causes of Iron Deficiency despite eating iron rich foods

Back 16

- Insufficiency of pancreatic enzyme
- Abs to parietal cells
- Achloridria
- Gastic reconstruction
- Defects in cubulin or transcobalamin

Front 17

Can you trust a serum folate level?

Back 17

No because if a person just ate spinach then the serum folate could be normal. Look at Neutrophils (for hypersegmentation) and look at RBCs.

Front 18

Folate
Normal Serum Level

Back 18

2.5-20 ng/ml
- low in Folate Deficiency
- normal in B12 Deficiency

Front 19

Homocysteine
Normal Serum Level

Back 19

200-900 pg/ml
- normal in Folate Deficiency
- low in B12 Deficiency

Front 20

Cobalamin
Normal Serum Level

Back 20

5-16 uM
- High in B12 Deficiency and in Folate Deficiency

Front 21

Methylmalonic Acid
Normal Serum Level

Back 21

70-270 nM
- High in B12 Deficiency
- normal in Folate Deficiency

Front 22

Karyorrhexis

Back 22

A stage of cellular necrosis in which the fradments of the nucleus fragments and its chromatin are distributed irregularly throughout the cytoplasm

Front 23

Does MCV vary with age?

Back 23

NO. If a patient has a change in MCV there is something pathologic occuring .: you must check for nutritional deficiencies.

Front 24

Does having 1 hypersegemtned neutriphil indicate that there is a pathologic indication?

Back 24

No, in order to have the classification of hypersegmented nutriphils you must have:
- 1 six-lobed neutrophil
- 5 five lobed neutriphils/ 100 cells

Front 25

Why would someone will macrocytic cells have an increased lactate dehydrogenase?

Back 25

there is high cell turnover because macrocytic cells are fragile

Front 26

Anisocytosis

Back 26

RBC descriptor to describe
- size variation

Front 27

Where do you see megaloblastosis in nutritional deficiencies?

Back 27

In all proliferating cell lines:
including epithelial cells lining the gastrointestinal tract (buccal mucosa, tongue, small intestine), cervix, vagina, and uterus
- But the megaloblastic changes are most striking in the blood and bone marrow

Front 28

Clinical Manifestations of Cobalamin and Folate Deficiency

Back 28

- Glossitis
- Secondary malabsorption caused by megaloblastic gastrointestinal changes
- Weight loss or Growth Failure
- Infertility
- Thrombosis
- Hyperpigmentation
- Immune deficiency

Front 29

Glossitis

Back 29

Beefy red tongue

- seen in B12 and folate defiencies

Front 30

Pernicious Anemia

Back 30

- anemia (autoimmune loss of gastric intrinsic factor) is the most common cause of megalobastic anemia worldwide, especially in persons of African or European ancestry
- a chronic progressive anemia of older adults due to failure of absorption of vitamin B12, usually associated with decreased intrinsic factor, characterized by numbness and tingling, weakness, and a sore smooth tongue, as well as dyspnea after slight exertion, faintness, pallor of the skin and mucous membranes, anorexia, diarrhea, loss of weight, and fever

Front 31

Neuropsychiatric Manifestations
B12 deficiency

Back 31

- Peripheral neuropathies
- Dorsal column involvement (loss of position and vibratory sense, ataxia)
- Subacute combined degeneration of spinal cord
- Psychiatric symptoms (dementia, psychosis)

Front 32

Treatment of B12 and Folate Deficiency

Back 32

- 1000 ug B12 weekly by IM injection x 8 weeks then monthly for life
- Consider oral therapy with close monitoring
- Folate 1 mg po per day

Front 33

Why should you always check for folate and B12 deficiency instead of just fixing one?

Back 33

Warning: Folate repletion without B12 repletion may normalize MCV and Hgb but allow neurologic manifestions to persist

Front 34

Schilling Test

Back 34

Part 1: Give radioactive cobalamin by mouth. After 1 hour, give injection of unlabelled cobalamin by injection (“flushing dose”) to saturate plasma B12 binders so that labeled cobalamin will not bind but be excreted via the kidney
Part 2: Give exogenous intrinsic factor with the radiolabeled cobalamin.

Front 35

Schilling Test at Part 1
Results for Patients with Pernicious Anemia

Back 35

An individual with pernicious anemia would absorb little or none of the oral B12 since these patients lack intrinsic factor. The amount of radiolabeled B12 recovered in the urine would be less than normal.

Front 36

Schilling Test at Part 2
Results for Patients with Pernicious Anemia

Back 36

In a patient with pernicious anemia, this should correct the absorption and increase the urinary excretion into the normal range.
If still abnormal, then the small intestine can’t absorb the B12-IF complex.

Front 37

If you do not have macrocytosis can you have a nutritional deficiency?

Back 37

Yes, you can still have folate or cobalamin deficiency

Front 38

What is the most senstive indicator for cobalamin deficiency?

Back 38

methylmalonic acid

Front 39

Causes of folate deficiency

Back 39

- diet lacking fruits and veggies
- alcoholism
- sprue, chron's dz...
- increased cellular proliferation
- pregnancy
- skin diseases
- hemolysis
- malignancies
- Drugs (antifolates and anticonvulsants)