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

Question 1

List 3 acquired causes of megaloblastic anemia

Answer 1

• Acquired
  
  • B12 deficiency
  • B9 (folic acid) deficiency
  • Drugs (HIV therapies, chemotherapy)

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 start iron

Question 3

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

Answer 3

• Hypersegmentation of the neutrophils (has more than four lobes)
• Macro-ovalocytes
  
  • Large, oval-shaped blood cells
• Low blood counts overall

Question 4

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

Answer 4

• B9 deficiency
  
  • High homocysteine
  • Normal methylmalonate
• B12 deficiency
  
  • High homocysteine (need b12 for methyl transfer for methionine production)
  • High methylmalonate (need B12 for hydrogen trasnfer for produce succinyl COA)

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 B9 or B12 deficiency?

Answer 5

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*

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 ferritin
• -> Ferritin increases, but cannot be delivered to erythroid marrow (also, ferritin is an acute phase reactant)
  
  • ​vs. IDA, where ferritin is reduced

Question 7

What are the dietary sources of B12?

Answer 7

Meat, eggs, dairy

Body can store 3-4 years => dietary deficiency alone usually does not cause B12 deficiency

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

​Think about this as anemia of inflammation! Hepcidin will increase so:​

• Iron: Low
• % saturation: Low
• Iron binding capacity (IBC or TIBC): Normal
• Ferritin: High
  
  • serum iron decreases, so ferritin rises as iron is sequestered in storage sites
  • also ferritin is an acute phase reactant so it will increase

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

• Brain and cranial nerves –> dementia, personality changes
• Neuropathy –> loss of vibratory and position sense, abnormal sensations of hands and feet

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
  
  • ​main storage protein for iron

Hemochromatosis = defect in hepcidin -> Ferroportin is able to absorb a ton of iron from the gut

Question 13

List 4 risk factors for copper deficiency

Answer 13

• Gastric bypass
• Celiac disease
• Excess zinc
• TPN

Presents similarly to bone marrow disease (MDS); rule out before beginning aggressive tx

Question 14

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

Answer 14

Iron sufficiency/overload

Inflammation (IL-6)

Question 15

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

Answer 15

Rule out bleeding

Then, figure out the underlying disease process

IDA is always caused by an underlying disease or bleeding

Question 16

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

Answer 16

Hypercellular

It is a megaloblastic anemia –> Low peripheral blood counts with hypercellular marrow

Question 17

What is the most common type of anemia worldwide?

Answer 17

Iron deficiency anemia

Question 18

What is the treatment for anemia of inflammation?

Answer 18

Treat whatever is causing the inflammation

(Interrupt IL-6 signaling)

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

Question 19

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

Answer 19

Hematologic symptoms (megaloblastic anemia)

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

Question 20

Will hepcidin be upregulated or downregulated in iron deficiency anemia?

How would this affect ferroportin?

Answer 20

Downregulated hepcidin

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

Question 21

List 2 functions of ferroportin

Answer 21

1. Iron absorption from gut enterocytes -> plasma
2. Iron transport from hepatocytes -> macrophages

Inhibited by hepcidin

Question 22

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

Answer 22

• 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 23

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

Answer 23

serum iron / iron binding capacity (aka transferrin)

Question 24

Describe the absorption of B12

Answer 24

1. B12 comes from the diet (meat, dairy, eggs)
2. B12 is liberated from binding proteins by gastric acid in the stomach
3. B12 binds salivary haptocorrin (HC)
4. B12 released from HC by pancreatic proteases in the duodenum
5. B12 binds intrinsic factor (from gastric parietal cells)
6. B12-IF complex is absorbed in the ilium
7. in blood stream, B12 binds to transcobalamin (TC) and then is stored in the liver

• 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 25

Vocabulary review:

• Ferritin:
• Transferrin:
• TIBC:

Answer 25

• 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 26

What are the dietary sources of folate?

Answer 26

Leafy green vegetables

Question 27

What protein helps absorb iron?

Answer 27

Ferroportin

Iron transport through ferroportin is regulated by hepcidin

Question 28

Which protein is the major regulator of iron absorption?

Answer 28

Hepcidin

• Iron is absorbed through ferroportin
• Hepcidin decides if this happens or not

Question 29

List the symptoms of iron deficiency anemia (4)

Answer 29

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

Question 30

What is pernicious anemia?

How does it affect B12?

Answer 30

• 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 31

What is ferritin?

Answer 31

main storage protein for iron

Question 32

What is transferrin?

Answer 32

Transport protein for iron, can be reported as total iron binding capacity (TIBC)