ICL 2.1: Disorders of Iron Metabolism Flashcards
what are normal Hb concentrations in men and women?
men: 14-16 g/dL
female: 12-14 g/dL
whats the normal RBC count in men and woman?
men: 4.3-5.9 million/mmˆ3
women: 3.5-5 million/mmˆ3
how much of iron can you absorb from food?
only 10%!
so if you put someone on iron pills, you want them to be on like 3 pills!
how does iron get into your body?
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
where does most of the iron absorbed by food go to?
- hemoglobin/RBC production (75%)
- ferritin that stores iron in liver & heart (10-20%)
- other (5-15%)
what inhibits ferroportin?
ferroportin transports iron out of the enterocyte into the blood
hepcidin released from the liver inhibits ferroportin
what regulates iron metabolism?
hepcidin!
hepcidin is a negative influencer of iron
so more iron you have, the less hepcidin and vice versa
what inhibits hepcidin?
- RBC production
- growth factors
- testosterone
this is why men have more hemoglobin!
what stimulates hepcidin secretion?
- high iron levels
2. inflammation
low MCV with normal iron is usually what?
hemoglobin problems!
this is your clue that it’s a hemoglobinopathy like thalassemia or sickle cell
what is TACO?
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
what’s the formula for MCH?
(Hb/RBC count)x10
mean corpuscular hemoglobin = average amount of Hb in RBCs in the body
what’s the formula for MCHC?
Hb concentration per gm/dL of RBC
mean cell hemoglobin concentration = average concentration of Hb in a given volume of blood
how is the MCH effected in IDA and thalassemia?
low
how is the MCHC effected in IDA and thalassemia?
low
in what anemias is MCHC high?
HbC
intra-cellular dehydration
H. spherocytosis
what’s the Hb threshold that people will get transfusions?
Hb = 7, then they will give a transfusion
what conditions increase iron demand?
pregnancy and lactation
during pregnancy iron is diverted to developing fetus
men shouldn’t be anemic unless they’re bleeding somewhere
can someone be iron deficient and still have normal Hb levels?
yes
what does and IDA blood smear look like?
RBCs look mostly white because there’s no iron!
you’ve lost the central pallor
what is sideroblastic anemia?
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
what causes sideroblastic anemia?
- chronic alcoholism
- B6 deficiency
- lead poisoning
what’s the inheritance pattern of sideroblastic anemia?
X linked recessive
what causes anemia of chronic disease?
iron overload! caused by:
- chronic inflammatory disease: like infections or sarcoidosis
- malignant disease: like lymphoma or sarcoma
not related to bleeding!!
what are the types of bone marrow failure anemias?
this is when your bone marrow isn’t making any RBCs and is filled with fat so the blood smear looks mostly white
- acquired
- congenital
which anemias are acquired bone marrow failure anemias?
- myelodysplastic syndrome
2. acquired aplastic anemia
which anemias are congenital bone marrow failure anemias?
- Fanconi anemia
- dyskeratosis congenita
- Shwachman-Diamond Syndrome
- severe congenital neutropenia
- Diamond-Blackfan anemia
- congenital megakaryocytic thrombocytopenia
in what population is iron overload most common?
Celtic course
irish, scottish people
what is hemochromatosis?
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
what is hemochromatosis inherited?
autosomal recessive
Celtic curse! Aka very common in Ireland and Scotland
Think, the liver turns rusty red color and scottish people have red hair!
what are the types of hemochromatosis?
- HFE
- TfR2
- HJV or HAMP
- ferroportin disease
what’s a clinical presentation of hemochromatosis?
bent looking fingers from the iron deposits in the skin
what’s the most common mutation that causes hemochromatosis?
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
can you get hemochromatosis from blood transfusions?
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
how many units of blood would cause an iron overload?
the body can’t regulate iron loss, the only way to get rid of it is chelate
20 units
what CBC values are diagnostic of hemochromatosis and iron overload?
high ferritin
high % transferrin saturation (>60%)
what’s a good way to see how much iron is in the liver without a biopsy to test for hemochromatosis/iron overload?
superconducting quantum interference device = SQUID
high power magnetic field
iron interferes with field
however there’s only 4 machines in the whole world….
how do you treat hemochromatosis?
- phlebotomy
take out blood every few weeks to decrease amount of iron
- deferasirox is an alternative
what’s the goal ferritin level for someone undergoing treatment for hemochromatosis?
<50 ug/L
