Anemia - Intro (complete)

Question 1

What is anemia?

Answer 1

Insufficient red cell mass to adequately deliver oxygen to peripheral tissues

Question 2

Which aspects of a CBC help determine whether or not a pt has anemia?

Answer 2

1) [Hb]
2) MCV
3) RDW
4) WBC count/differential
5) Platelet count

Also, cell morphology on a smear, retic count, and retic index

Question 3

Define reticulocyte count

Answer 3

% of reticulocytes of 1000 RBCs

Normal: 0.4 - 1.7%

Increased RBC production: 3.5-5 fold increase

Question 4

Define absolute reticulocyte count

Answer 4

% of reticulocytes x RBC count

Helps determine relevance of retic count

> 50,000/microL = ^ from baseline RBC production

Question 5

Define reticulocyte index

Answer 5

RI = Retic count x (pt Hb/normal Hb) x (1/Stress factor)

Normal RI = 1 to 2
Decreased production RI = 2

Corrects the retic count for [RBC] and stress reticulocytosis

Question 6

What are the parameters for ‘stress factor’ used to calculate the reticulocyte index?

Answer 6

Stress factor =

• 1.5 (mild anemia >/= 9gm/dl)
• 2.0 (moderate 6.5-9)
• 2.5 (severe <6.5)

Question 7

What are the critical findings in the history that help determine the cause of anemia?

Answer 7

• Acute or chronic?
• Past Med: Occupation, exposure to toxins, travel, drugs
• Fam History: gallstones, jaundice, splenomegaly, splenectomy, cholecystectomy

Question 8

What are the critical findings in the physical exam that help determine the cause of anemia? (scroll alllll the way down)

Answer 8

Symptoms:

1) SOB
2) Fatigue
3) Rapid HR
4) Dizziness
5) Claudication
6) Angina
7) Pallor

Signs:

1) Tachycardia
2) Tachypnea
3) Dyspnea
4) Pallor

Question 9

What is the general classification scheme of anemias based on reticulocyte count?

Answer 9

Assuming there are no add’l hematologic abnormalities…

Is there an increase in retic count?

If yes, then probably an ^ in hemolysis or hemorrhage —»> now look at bilirubin, LDH, haptoglobin, hemosiderin (for hemolysis)

If no, examine the MCV

GO LOOK AT THAT MASSIVE FLOW CHART

Question 10

What is the general classification scheme of anemias based on mean corpuscular volume (MCV)?

Answer 10

If the retic count is normal, look at the MCV

MCV>100 = macrocytic anemia

MCV 80-100 = normocytic

MCV <80 = microcytic

GO LOOK AT THAT MASSIVE FLOW CHART

Question 11

Describe general iron metabolism

Answer 11

1) Fe has 2 valence states (ferric+++ and ferrous++)
2) Fe forms insoluble hydroxides in aq — unless protein bound
3) Fe salts more soluble at low pH
4) Fe balance is controlled by absorption
5) Small losses of Fe (no mechanism for excretion)
6) Absorbed in the duodenum

Question 12

Describe the iron cycle

Answer 12

• Fe is recyclable
• When through mucosal cell, binds to transferrin (2 moles of ferric)
• Transferrin goes to BM/maturing normoblasts
• Binds to surface transferrin receptors and endocytoses the Fe-Transferrin complex
• Endosome breaks it down, separating Trans and Fe
• Fe is directed to maturing normoblast —» incorporated to Hb
• Mature RBC circulates for 120 days –» spleen
• Macros in spleen sequester Fe in intracellular Ferritin
• Fe can be released by ferritin from cell and then bound by Transferrin

AND WE BEGIN AGAIN!

Question 13

Describe iron absorption

Answer 13

Fe from diet
—»>
gastric pH and gastroferrin maintain solubility til duodenum
—»>
absorption in duodenum at mucosal surface as ferric Fe
—»>
ferric reduced to ferrous by surface reductase
—»>
enters cell through DMT1 (Fe transporter)
—»>
some ferrous bind to ferritin (stored in cell)
—»
some transported across baso-lat by ferroportin transporter

Question 14

What are some factors that increase Fe absorption?

Answer 14

1) Presence of protein (e.g. AAs) — to bind Fe for ^ solubility
2) Vit C — maintains Fe in appropriate valence state
3) Increased [Fe] presented to duodenum
4) Increased erythropoietic activity (need more Fe for new cells)

Question 15

What are some factors that decrease Fe absorption?

Answer 15

1) Phytates
2) Oxalates
3) Certain foods can precipitate Fe

Question 16

What is hepcidin?

Answer 16

• A 25 AA peptide produced by hepatocytes
• ^ synthesis b/c of Fe overload

At high levels:

• Plasma flow from stores is decreased
• Fe saturation of transferrin is decreased
• Binds to ferroportin causing its degradation — less Fe exported out of cell
• Increased Fe in ferritin

Question 17

Where is Fe distributed in the body?

Answer 17

1) Hb (65%)
2) Myoglobin (6%)
3) Transferrin (0.1%)
4) Ferritin (13%)
5) Hemosiderin (12%)
6) Other… (3.6%)

Question 18

What are some of the major causes of Fe deficiency?

Answer 18

1) Decreased Fe intake (e.g. diet, impaired absorption)
2) Increased Fe loss (e.g. bleeding, excessive menstruation)
3) Increase Fe requirements (e.g. preggers)
4) Inadequate presentation of erythroid precursors
5) Abnormal Fe balance

Question 19

What are the hematologic changes associated with the development of Fe deficiency?

Answer 19

1) Decrease in Hb
2) Decrease in cell proliferation
3) Mild hemolysis b/c of ^ rigidity of cells produced under Fe deficient conditions

Question 20

Describe stage 1 of Fe deficiency

Answer 20

AKA: Fe depletion

1) Decrease in ferritin
2) Normal Fe serum
3) Normal transferrin saturation
4) Normal Hb stores
5) Normal erythropoiesis
6) Increase Fe absorption

Question 21

Describe stage 2 of Fe deficiency

Answer 21

AKA: Fe Deficient Erythropoiesis

1) Fe stores depleted (ferritin)
2) Decrease Fe serum
3) Increase in Fe binding capacity
4) Fe loading in normoblasts becomes impaired
5) Normal erythropoiesis
6) Increase RBC protoporphyrin

Question 22

Describe stage 3 of Fe deficiency

Answer 22

AKA: Fe Deficiency Anemia

1) Increase in Transferrin
2) Low serum Fe
3) Transferrin absorption decreased
4) Increase RBC protoporphyrin
5) Cell produced are microcytic and hypochromic

Question 23

What are the laboratory findings associated with Fe deficiency anemia?

Answer 23

1) Decrease Hb
2) Decrease Hct
3) Decrease in production (low retic count/RI)
4) Low MCV
5) Increased RDW

Histo:

1) Microcytic
2) Elliptocytes
3) Fragmented RBCs
4) Spherocytes
5) Target cells

Question 24

Describe the causes of over accumulation of Fe in the body

Answer 24

1) Increase in Fe intake (diet)
2) Increase absorption (hemochromatosis) — b/c of HLA-H mutation
3) Repeated transfusions

Question 25

Describe the effects of over accumulation of Fe in the body

Answer 25

Organ damage

1) Heart (arrhythmia, CHF)
2) Liver (dysfunction, failure)
3) Endocrine organs (pancreas function, diabetes)

Question 26

What are two treatments for Fe overload?

Answer 26

1) Phlebotomy

2) Fe chelators

Question 27

Describe phlebotomy as a treatment for Fe overload

Answer 27

Used when there’s an ^ in absorption

Reduces Fe burden until Ferritin is in normal range

Question 28

Describe Fe chelators as a a treatment for Fe overload

Answer 28

Used b/c of transfusions

Return Fe levels to normal