Iron homeostasis & Iron deficiency anemia

Question 1

Complete blood count: what values are given on the “X” in a patient’s chart

Answer 1

Question 2

Spherocytes

Answer 2

Round red blood cells

Question 3

Poikilocytosis

Answer 3

Weird, variable forms of RBC

Question 4

Anisocytosis

Answer 4

Variable size of RBCs

Question 5

What test can distinguish hypoproliferative v. hyperproliferative anemia?

Answer 5

Reticulocyte count! Measures trhe health of the bone marrow

If low, it’s hypoproliferative

If high, it’s hyperproliferative

Question 6

What is anemia?

Answer 6

RBC <13 for men, <12 for women

Symptoms depends on acuity

Question 7

When should you transfuse an anemic patient?

Answer 7

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

Question 8

If your patient is anemic, which lab workups should you do and why?

Answer 8

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

Question 9

What is a normal absolute reticulocyte count? What does this tell you?

Answer 9

Normal is up to 100,000/microliter

More accurate way to assess body’s response to anemia

Question 10

What are possible causes of elevated reticulocyte count?

Answer 10

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

Question 11

What are possible causes of a decreased reticulocyte count?

Answer 11

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

Question 12

Which places do you have iron in your body? “compartments”

Answer 12

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

Question 13

How much iron should you have daily?

Answer 13

Men: 1 mg/day, 1.3 during adolescence

Women: 1.5 mg/day; 2.5 when pregnant, 1 post-menapause

Question 14

How is iron absorbed in the gut?

Answer 14

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)

Question 15

What’s the progression of findings in iron deficiency anemia?

Answer 15

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

Question 16

What are the symptoms of iron deficiency?

Answer 16

Fatigue

Dyspnea on exertion

Atrophic glossitis

Cracking at side of mouth

Pica (craving non-foods- ice, rice, sand)

Koilonychia (nail spooning)

Esophageal web

Question 17

Ferritin

Answer 17

Reflects iron stores

Question 18

Transferrin

Answer 18

Blood plasma binding protein that binds iron and transports it in plasma

Question 19

Serum iron

Answer 19

Measures levels of transferrin bound to iron

Question 20

TIBC

Answer 20

transferrin iron binding capacity

Measures all the bound iron in blood, which is predominantly transferrin

Question 21

What is the normal response to iron therapy?

Answer 21

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

Question 22

What are the findings of anemia of chronic disease?

Answer 22

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)

Question 23

What is hepcidin?

Answer 23

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

Question 24

What do serum iron, transferrin, and ferritin look like in iron deficiency vs. anemia of chronic dz?

Answer 24

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)

Question 25

What is hemochromatosis?

Answer 25

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

Question 26

What are the features of hemochromatosis?

Answer 26

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

Question 27

What is the treatment for hemochromatosis?

Answer 27

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