Iron homeostasis & Iron deficiency anemia Flashcards
Complete blood count: what values are given on the “X” in a patient’s chart
Spherocytes
Round red blood cells
Poikilocytosis
Weird, variable forms of RBC
Anisocytosis
Variable size of RBCs
What test can distinguish hypoproliferative v. hyperproliferative anemia?
Reticulocyte count! Measures trhe health of the bone marrow
If low, it’s hypoproliferative
If high, it’s hyperproliferative
What is anemia?
RBC <13 for men, <12 for women
Symptoms depends on acuity
When should you transfuse an anemic patient?
Consider how the patient looks
Always transfuse if Hb is around 7
Maybe transfuse if Hb <8 but not cardiac symptoms: consider how the patient looks
Transfuse if Hb <10 if active cardiac ischemia
If your patient is anemic, which lab workups should you do and why?
Do lab work ups to understand the underlying cause of the anemia. Anemia is almost always secondary to another cause!!
CBC
Reticulocyte count
hyperproliferative: healthy marrow
hypoproliferative: sick marrow
MCV: mean cell volume
RDW: red cell distribution width
- if it’s large, they have a variety of red cell sizes
What is a normal absolute reticulocyte count? What does this tell you?
Normal is up to 100,000/microliter
More accurate way to assess body’s response to anemia
What are possible causes of elevated reticulocyte count?
Increased red cell turnover due to:
Blood loss: internal or external bleed
- *Hemolytic anemia**: person is destroying their own red cells yet they have a healthy production of red cells from the bone marrow; their count will increase to compenaste
- Inherited: sickle cell, thalassemia major, hereditary spherocytosis
- Acquired: autoimmune hemolytic anemia, thrombotic thrombocytopenic purpura, microangiopathic hemolytic anemia, infections
What are possible causes of a decreased reticulocyte count?
Lack of nutrients: most common! iron, B12, or folate deficiency
Bone marrow failure: aplastic anemia, PRCA (antibodies against red cell precurosors in the bone marrow), tumor infiltration
Bone marrow suppression: medications i.e. bactram, HIV meds; chemotherapy, radiation
Low level of trophic hormones: renal failure (not enough erythropoitin produced to turn on RBC production), hypothyroidism (thyroid hormone also required to make & mature red cells)
- *Anemia of chronic dz/inflammation**: often difficult to decide where it’s coming from
- hepcidin levels increase
Which places do you have iron in your body? “compartments”
Hemoglobin: 67%/2000 mg
Storage iron (ferritin, hemosiderin): 27%
Myoglobin iron (muscle): 3.5%
Labile pool (transport forms of Fe) 2.2%
Other tissue iron 0.2%
Transport iron 0.08%
Note there should never be free iron in the circulation bc its a free radical; can happen in severe iron overload= bad news
How much iron should you have daily?
Men: 1 mg/day, 1.3 during adolescence
Women: 1.5 mg/day; 2.5 when pregnant, 1 post-menapause
How is iron absorbed in the gut?
Divalent transport
DMT-1 transports iron across the brush border at the apex of the villus
HFE on the basolateral surface of the crypt cells & regulates absorption of iron & you get iron released into the blood (ferritin)
What’s the progression of findings in iron deficiency anemia?
Stainable iron decreases: see on bone marrow biopsy
Serum ferritin decreases: if less than 10, definitely iron deficiency; if >100, definitely not iron deficiency; if between, you have to check other lab values to determine if iron deficient
Desaturation of transferrin
Serum iron decreases
Transferrin iron binding capacity increases
Blood smear changes: microcytic, hypochromic, aniso & poikilocytosis
Anemia/symptoms develop
What are the symptoms of iron deficiency?
Fatigue
Dyspnea on exertion
Atrophic glossitis
Cracking at side of mouth
Pica (craving non-foods- ice, rice, sand)
Koilonychia (nail spooning)
Esophageal web
Ferritin
Reflects iron stores
Transferrin
Blood plasma binding protein that binds iron and transports it in plasma
Serum iron
Measures levels of transferrin bound to iron
TIBC
transferrin iron binding capacity
Measures all the bound iron in blood, which is predominantly transferrin
What is the normal response to iron therapy?
Initial response takes 7-14 days
Modest reticulocytosis (7-10%) = these come out first
Correction of anemia requires 2-3 months
6 months of therapy beyond correction of anemia needed to replete stores, assuming no other loss of blood/iron malabsorption
What are the findings of anemia of chronic disease?
Mild, non-progressive anemia (Hgb around 10, Hct around 30%)
WBC and Plt count normal
Normochromic/normocytic RBC (though up to 30% can be hypochromic and microcytic)
Mild aniso- & poikilocytosis
Somewhat shortened RBC survival
Normal reticulocyte count (inappropriately low for the degree of anemia, indicating there’s something preventing the person from making enough RBCs)
Normal bilirubin (no hemolysis)
Erythropoietin levels increased but blunted for degree of anemia (lack ability to incorporate enough iron into the heme molecule)
What is hepcidin?
25 amino acid antimicrobial polypeptide produced in liver
Upregulated in inflammatory/infectious states (causing decreased iron absorption seen in AOCD), down-regulated in iron deficiency
Binds to & causes internalization of ferroportin, leading to decreased iron uptake from GI tract
Also blocks macrophage iron release
What do serum iron, transferrin, and ferritin look like in iron deficiency vs. anemia of chronic dz?
Serum iron:
Decreased in BOTH Fe deficiency and AOCD
Transferrin:
High in Fe deficiency
Low in AOCD
Ferritin: look at this first; reflects intracellular stores and extreme values help you rule in/out
Low in iron deficiency (<10)
High in AOCD (>100)
What is hemochromatosis?
Dz of excess iron uptake; autosomal dominant dz
More common in Norhtern Europe; can also be acquired from transfusion
Defect in DMT-1 (divalent metal transporter-1) or human hemochromatosis protein (HFE)
You get increased transferrin saturation (serum iron/TIBC)
Normal 33%, >60% marker of this dz; if 90% you get free radical iron in circulation
Increased ferritin (storage form of Fe)
Iron deposition in tissues –> multiorgan dysfunction
What are the features of hemochromatosis?
All secondary to iron deposition in your organs!!
Skin: skin gets darker
Endocrinopathy: diabetes, hypothyroidism, hypopituitarism
Liver damage: cirrhosis, hepatocellular carcinoma
Cardiac damage: cardiomyopathy –> CHF
Arthritis
What is the treatment for hemochromatosis?
Early recognition, bc if you have end stage organ failure, there isn’t much you can do
Phlebotomy:remove enough blood so pt becomes iron deficient & uses the ferritin (storage iron) to make red cells
Iron chelation: in transfusion induced hemochromatosis
Liver transplantation: if liver failure/hepatic carcinoma
Gene therapy to restore the normal function HFE
