ICL 2.1: Disorders of Iron Metabolism

Question 1

what are normal Hb concentrations in men and women?

Answer 1

men: 14-16 g/dL
female: 12-14 g/dL

Question 2

whats the normal RBC count in men and woman?

Answer 2

men: 4.3-5.9 million/mmˆ3
women: 3.5-5 million/mmˆ3

Question 3

how much of iron can you absorb from food?

Answer 3

only 10%!

so if you put someone on iron pills, you want them to be on like 3 pills!

Question 4

how does iron get into your body?

Answer 4

Fe+3 from food gets turned into Fe+2 (because only Fe+2 can get into the body!)

Fe+2 goes into enterocyte via DMT1 transporter in apical membrane

Fe+2 leaves enterocyte via Ferroportin 1 transporter in basolateral membrane

Fe+2 gets turned into Fe+3

Fe+3 binds to transferrin and transferrin takes Fe+3 to wherever its needed in the body

Question 5

where does most of the iron absorbed by food go to?

Answer 5

1. hemoglobin/RBC production (75%)
2. ferritin that stores iron in liver & heart (10-20%)
3. other (5-15%)

Question 6

what inhibits ferroportin?

Answer 6

ferroportin transports iron out of the enterocyte into the blood

hepcidin released from the liver inhibits ferroportin

Question 7

what regulates iron metabolism?

Answer 7

hepcidin!

hepcidin is a negative influencer of iron

so more iron you have, the less hepcidin and vice versa

Question 8

what inhibits hepcidin?

Answer 8

1. RBC production
2. growth factors
3. testosterone

this is why men have more hemoglobin!

Question 9

what stimulates hepcidin secretion?

Answer 9

1. high iron levels

2. inflammation

Question 10

low MCV with normal iron is usually what?

Answer 10

hemoglobin problems!

this is your clue that it’s a hemoglobinopathy like thalassemia or sickle cell

Question 11

what is TACO?

Answer 11

Transfusion Associated Cardiac Overload

sometimes happens with blood transfusions

features: dyspnea, hypertension, crepitations, low O2 saturation

risk of volume overload/respiratory distress especially in small/elderly patients

avoidable by careful attention to fluid balance

Question 12

what’s the formula for MCH?

Answer 12

(Hb/RBC count)x10

mean corpuscular hemoglobin = average amount of Hb in RBCs in the body

Question 13

what’s the formula for MCHC?

Answer 13

Hb concentration per gm/dL of RBC

mean cell hemoglobin concentration = average concentration of Hb in a given volume of blood

Question 14

how is the MCH effected in IDA and thalassemia?

Answer 14

low

Question 15

how is the MCHC effected in IDA and thalassemia?

Answer 15

low

Question 16

in what anemias is MCHC high?

Answer 16

HbC

intra-cellular dehydration

H. spherocytosis

Question 17

what’s the Hb threshold that people will get transfusions?

Answer 17

Hb = 7, then they will give a transfusion

Question 18

what conditions increase iron demand?

Answer 18

pregnancy and lactation

during pregnancy iron is diverted to developing fetus

men shouldn’t be anemic unless they’re bleeding somewhere

Question 19

can someone be iron deficient and still have normal Hb levels?

Answer 19

yes

Question 20

what does and IDA blood smear look like?

Answer 20

RBCs look mostly white because there’s no iron!

you’ve lost the central pallor

Question 21

what is sideroblastic anemia?

Answer 21

iron is present but can’t be used

it gets stuck in the mitochondria of early RBCs

defect in heme synthesis within the mitchondria of developing RBCs in the bone marrow

iron accumulates mitochondria which produces ringed sideroblasts

Question 22

what causes sideroblastic anemia?

Answer 22

1. chronic alcoholism
2. B6 deficiency
3. lead poisoning

Question 23

what’s the inheritance pattern of sideroblastic anemia?

Answer 23

X linked recessive

Question 24

what causes anemia of chronic disease?

Answer 24

iron overload! caused by:

1. chronic inflammatory disease: like infections or sarcoidosis
2. malignant disease: like lymphoma or sarcoma

not related to bleeding!!

Question 25

what are the types of bone marrow failure anemias?

Answer 25

this is when your bone marrow isn't making any RBCs and is filled with fat so the blood smear looks mostly white 1. acquired 2. congenital

Question 26

which anemias are acquired bone marrow failure anemias?

Answer 26

1. myelodysplastic syndrome | 2. acquired aplastic anemia

Question 27

which anemias are congenital bone marrow failure anemias?

Answer 27

1. Fanconi anemia 2. dyskeratosis congenita 3. Shwachman-Diamond Syndrome 4. severe congenital neutropenia 5. Diamond-Blackfan anemia 6. congenital megakaryocytic thrombocytopenia

Question 28

in what population is iron overload most common?

Answer 28

Celtic course irish, scottish people

Question 29

what is hemochromatosis?

Answer 29

excessive iron accumulation in the liver from the due due to abnormal absorption of normal iron intake resulting in organ dysfunction iron also deposits in pancreas, heart, adrenal, thyroid, parathyroid, anterior pituitary, literally everywhere liver turns rusty brown color from hepatocytes dying

Question 30

what is hemochromatosis inherited?

Answer 30

autosomal recessive Celtic curse! Aka very common in Ireland and Scotland Think, the liver turns rusty red color and scottish people have red hair!

Question 31

what are the types of hemochromatosis?

Answer 31

1. HFE 2. TfR2 3. HJV or HAMP 4. ferroportin disease

Question 32

what's a clinical presentation of hemochromatosis?

Answer 32

bent looking fingers from the iron deposits in the skin

Question 33

what's the most common mutation that causes hemochromatosis?

Answer 33

HFE gene mutation C282Y point mutation that causes cysteine to tyrosine substitution penetrance is low though, lots of people have the mutation but don't actually experience Fe overload

Question 34

can you get hemochromatosis from blood transfusions?

Answer 34

no the iron overload from a transfusion gets deposited in a different place in hemochromatosis, iron is deposited mainly in liver cells while in a transfusion it's in macrophages

Question 35

how many units of blood would cause an iron overload?

Answer 35

the body can't regulate iron loss, the only way to get rid of it is chelate 20 units

Question 36

what CBC values are diagnostic of hemochromatosis and iron overload?

Answer 36

high ferritin high % transferrin saturation (>60%)

Question 37

what's a good way to see how much iron is in the liver without a biopsy to test for hemochromatosis/iron overload?

Answer 37

superconducting quantum interference device = SQUID high power magnetic field iron interferes with field however there's only 4 machines in the whole world....

Question 38

how do you treat hemochromatosis?

Answer 38

1. phlebotomy take out blood every few weeks to decrease amount of iron 2. deferasirox is an alternative

Question 39

what's the goal ferritin level for someone undergoing treatment for hemochromatosis?

Answer 39

<50 ug/L