247/248: Other Anemias (Iron/Chronic Disease, Megaloblastic)

Question 1

What are the two main causes of megaloblastic anemia?

Answer 1

• B12 deficiency
• B9 (folic acid) deficiency

Question 2

When is it appropriate to use iron to treat anemia of inflammation?

Answer 2

When there is a concurrent iron deficient state

If it’s just anemia of inflammation, don’t use iron

Question 3

What findings on peripheral blood smear are indicative of megaloblastic anemia? (3)

Answer 3

• Hypersegmented neutrophils (6+ lobes)
• Macrocytes and macro-ovalocytes
  
  • Large, oval-shaped blood cells
  • Increase in MCV
• Low blood counts overall

Question 4

How can levels of homocystine and methylmalonate differentiate between folate (B9) vs. B12 deficiency?

Answer 4

• Folate (B9 )deficiency
  
  • High homocysteine
  • Normal methylmalonate
• B12 deficiency (for B12, BOTH are high)
  
  • High homocysteine
  • High methylmalonate

Both will have megaloblastic anemia; only B12 deficiency will have neurologic sx (subacute combined degeneration)

Question 5

Is pure dietary deficiency more likely to cause Folate/B9 or B12 deficiency?

Answer 5

Folate/B9 deficiency

• B9 is found in leafy green vegetables; 3-4 months of body stores*
• B12 is found in meat, eggs, dairy; 2-4 years of body stores => deficiency likely results from malnutrition and malabsorption; look for other deficiencies*

Question 6

Describe the pathogenesis of anemia of inflammation (aka anemia of chronic disease)

Answer 6

It all starts with inflammatory stress

• -> Increased hepcidin
• -> Ferroportin is degraded
• -> Iron cannot be absorbed from the GI tract, and it is sequestered as ferrtin
• -> Ferritin increases, but cannot be delivered to erythroid marrow (also, ferritin is an acute phase reactant)
  
  • ​vs. IDA, where ferritin is reduced
  • Iron is in the body, just can’t be used

Question 7

What are the dietary sources of B12?

Answer 7

Meat, eggs, dairy

Not present in vegetables!

Body can store 2-4 years => dietary deficiency alone usually does not cause B12 deficiency0

Question 8

How will the following vary in a patient with anemia due to rheumatoid arthritis?

• Iron:
• % saturation:
• Iron binding capacity (IBC or TIBC):
• Ferritin:

Answer 8

• Iron: Low
• % saturation: Low
• Iron binding capacity (IBC or TIBC): Normal
• Ferritin: High

Anemia of chronic disease/inflammation

• -> Increased hepcidin*
• -> Iron sequestration in storage sites (Ferritin), but cannot be used bc hepcidin is degrading ferroportin*

Question 9

List 2 clinical scenarios where we would expect hepcidin to be suppressed

Answer 9

Iron deficiency

Hypoxia

Question 10

What is the first line treatment for hemochromatosis?

Answer 10

Phlebotomy

Only use iron chelation if a pt has concurrent anemia (low hemoglobin), and never use with hereditary hemochromatosis

Question 11

What CNS manifestation results from B12 deficiency?

Answer 11

Subacute combined degeneration

• Demyelination of neurons of the
  
  • Spinal column- parathesias of the hands and feet, loss of vibratory and position sense, unsteadiness of gait
  • Cerebral cortex- dementia, personality changes, distrubance in taste/smell

Question 12

How will the following vary in a patient with hemochromatosis?

• Iron:
• % saturation:
• Iron binding capacity (IBC or TIBC):
• Ferritin:

Answer 12

• Iron: High
• % saturation: High
• Iron binding capacity (IBC or TIBC): Normal or decreased
• Ferritin: High
• Hemochromatosis = defect in hepcidin , hepcidin is reduced*
• →Ferroportin always active→absorb way too much iron*

Question 13

List 2 clinical scenarios in which we would expect hepcidin to be upregulated

Answer 13

Iron sufficiency/overload

Inflammation (IL-6)→ anemia of inflammation/chronic disease

(Increased hepcidin→ decreased ferropotin→ decreased iron)

Question 14

What is the next step in evaluating a patient who has a new iron deficiency anemia?

Answer 14

Rule out bleeding

Then, figure out the underlying disease process

IDA is always caused by an underlying disease or bleeding

Question 15

Will the bone marrow be hypercellular or hypocellular in B12/folate deficiency?

Answer 15

Hypercellular

Low peripheral blood counts with hypercellular marrow => megaloblastic anemia

Question 16

What is the most common type of anemia worldwide?

Answer 16

Iron deficiency anemia

Question 17

What is the treatment for anemia of inflammation?

Answer 17

Treat whatever is causing the inflammation

(Interrupt IL-6 signaling)

Don’t give iron unless there is a concurrent iron-deficiency anemia

Question 18

Supplementing folate (B9) in vitamin B12 deficiency will improve which symptoms of B12 deficiency?

Answer 18

Hematologic (megaloblastic anemia)

Folate will NOT have any effect on the neurologic symptoms of B12 deficiency!

Question 19

Will hepcidin be upregulated or downregulated in iron deficiency anemia?

How would this affect ferroportin?

Answer 19

Downregulated hepcidin

• > Ferroportin channel expressed
• Hepcidin puts the brakes on iron absorption by inhibiting iron transport through ferroprotin (Hepcidin causes degradation of ferroportin)*

Question 20

List 2 functions of ferroportin

Answer 20

Iron transport from hepatocytes -> macrophages

Iron absorption from gut enterocytes -> plasma

Inhibited by hepcidin

Question 21

What is the difference between absolute and functional iron deficiency anemia?

Answer 21

• Absolute = truly there is not enough iron in the body
• Functional = Iron is there, but not available for use
  
  • Anemia of inflammation
  • Increased EPO (enough iron, but cannot keep up with new demand)

Question 22

What does % saturation measure? (In terms of iron stores)

Answer 22

Total iron / iron binding capacity

Question 23

Describe the absorption of B12

Answer 23

• B12 is liberated from binding proteins by gastric acid
• B12 binds salivary haptocorrin (HC)
• B12 released from HC by pancreatec proteases
• B12 binds intrinsic factor (from gastric parietal cells)
• B12-IF complex is absorbed in the ilium
• 3-4 years of body stores; malabsorption is more likely than malnutrition*
• Malabsorption may be caused by low gastric acid, gastric bypass, deficient IF, pancreatic insufficiency, intestinal diseases*

Question 24

Vocabulary review:

• Ferritin:
• Transferrin:
• TIBC:

Answer 24

• Ferritin: Storage form of iron (in macrophages)
• Transferrin: Transport protein for iron
  
  • When it’s time to use the iron, ferritin is bound to transferrin and it gets shipped wherever it needs to go
• TIBC: Total iron binding capacity
  
  • ​The amount of iron (ferritin) that the body’s transferrin is capable of binding

Note: As lab values, transferrin and TIBC measure essentially the same thing; transferrin is a direct measurement, and TIBC is an indirect measurement

Question 25

What are the dietary sources of folate/B9?

Answer 25

Leafy green vegetables

Question 26

What protein transports iron?

Answer 26

Ferroportin *Hepcidin leads to the degradation of ferroportin*

Question 27

Which protein is the major regulator of iron absorption?

Answer 27

Hepcidin * Iron is absorbed through ferroportin * Hepcidin decides if this happens or not * Hepcidin leads to the internalizatio and degradation of ferroportin

Question 28

List the symptoms of iron deficiency anemia (4)

Answer 28

* Anemia sx * Lightheaded, fatigued, dizzy, difficulty breathing * Epithelial depletion sx (cannot replenish) * Brittle nails, cracked lips, tongue sensitivity * Pica * Eating dirt or ice * Sx of underlying disease

Question 29

What is pernicious anemia? How does it affect B12?

Answer 29

* Auto-antibodies destroy gastric **parietal cells and intrinsic factor** * -\> Less HCL * -\> Less intrinsic factor * **Results in impaired B12 absorption** * Megaloblastic anemia * Subacute combined degeneration

Question 30

A young woman has anemia from heavy menstrual cycles. What would be the expected hepcidin and ferroportin levels?

Answer 30

Hepcidin- SUPPRESSED Ferroportin- EXPRESSED *Hepcidin is appropriated suppressed in IDA, so the ferroportin transporter is active, absorbing more iron.*

Question 31

Alcoholics with a poor diet are more likely to have ___________ deficiency.

Answer 31

Alcoholics with a poor diet are more likely to have **FOLATE/B9** deficiency