Heme Lecture Exam III

Where does the majority of your iron come from?

Recycled RBC's

What aids in iron absorption?

Ascorbic acid (vitamin C) and low pH/protons

What state does iron need to be in to cross membranes, and be active?

Fe 2+, reduced/ferrous state

What state does iron need to be in to be stored or transferred?

Fe 3+, oxidized/ferric state

What state is iron in naturally in food?

Fe 3+, oxidized/ferric state

How do low pH foods/ascorbic acid aid in iron absorption?

They provide the protons for reducing iron to Fe2+ state

How much iron does a person absorb in a day?

1mg of iron, or 10% of daily consumption

What is the name for serum ferroxidase?

Hephestin

What foods inhibit absorption of iron?

Caffeine (tea, coffee), grains, chocolate

What are the anemias of impaired iron utilization?

Iron deficient, chronic disorders, sideroblastic, lead poisoning

Is iron stored in hemosiderin easily accessible for use by the body?

No

Is iron stored in transferrin easily accessible for use by the body?

Yes

What could two cell populations witnessed in a peripheral blood smear indicate?

Either recent transfusion, iron therapy, or sideroblastic anemia

What could anisochromia witnessed in a peripheral blood smear indicate?

Iron therapy

Where is the iron in an iron deficiency anemia?

Nowhere

Where is the iron in a sideroblastic anemia?

In mitochondria of normoblasts within bone marrow

Where is the iron in hemochromatosis?

Parenchyma of organs (liver or spleen)

What might you witness in the peripheral blood of an iron deficient patient?

Microcytic, hypochromic RBCs, tailed elliptocytes, thrombocytosis

Why does thrombocytosis occur in iron deficient anemia?

Body detects lack of iron as blood loss, forms platelets in response

What vitamin could help sideroblastic anemia?

Vitamin B6, since it serves as a cofactor for heme synthesis

What could ragged RBCs witnessed in a peripheral blood smear indicate?

Iron deficiency in bone marrow

Where is iron absorbed?

In the jejunum and duodenum

What conditions or age ranges require increased need for iron?

1-2 years
Adolescents
Pregnancy

What conditions cause increased iron loss?

G.I. bleed, menstruation, hemolytic anemias

Where is the iron normally found in the body?

2/3 in hemoglobin within RBC
1/3 in storage (liver, spleen, bone marrow)

How is iron lost daily?

From lost cells shed from GI tract or skin, sweat, urine, blood loss, bile, lactation

What reaction occurs as iron is bound to transferrin?

Oxidation reaction

What is the carrier of iron?

Transferrin

What is the name of the common ferric reductase enzyme?

Duodenal cytochrome B (DCytB)

What is hemosiderin?

Detanured ferritin in lysosomal membranes

What does hemosiderin degrade to?

An amorphous crystal complex

What is ferritin composed of?

Apoferritin (acute phase reactant protein) and iron

Which receptor allows iron into the cell?

Divalent metal transporter 1 (DMT1)

Which receptor transports iron out of the cell?

Ferroportin (IREG1)

How many molecules of iron is transferrin capable of carrying?

Two

What is transferrin called when it binds one molecule of iron?

Monotransferritin

What is transferrin called when it binds two molecules of iron?

Differic transferritin

What does serum ferritin measure?

Mirrors total number of iron stores

What does serum iron measure?

Iron in transit between spleen/liver and bone marrow

What is TIBC?

Total iron binding capacity; ability of transferrin to carry iron

What is a high TIBC indicate?

High capacity to bind iron, meaning unsaturated transferrin (capable of binding more iron--and its failure to do so)

What condition is high TIBC indicative of?

Iron deficient anemia

What is FEP and ZPP?

Free erythrocytic protoporphyrin and Zinc protoporphyrin

What does a high value of FEP indicate?

A buildup of heme precursors as a result of blocked heme synthesis or unavailable iron

What happens in heme synthesis if iron delivery is insufficient?

Zinc takes the place of iron, forming zinc protoporphyrin (ZPP)

What condition might be identified by a high FEP/ZPP test?

Lead poisoning

When are sideroblasts in the bone marrow increased?

In sideroblastic anemia

What is the equation to find percent of transferrin saturation?

[(Serum Iron) / (TIBC)] x 100%

What percent transferrin saturation would indicate iron deficiency anemia?

Less than 16%

What percent transferrin saturation would indicate iron overload?

Over 50%

What does percent transferrin represent?

Amount of iron bound to transferrin in the blood

What is UIBC?

Unsaturated iron binding capacity

What is the equation for UIBC?

TIBC - Serum Iron

What does UIBC represent?

Amount of transferrin without iron bound

What is sTfR?

Serum/soluble transferrin receptors

What does a sTfR test measure?

Amount of transferrin receptors; made in response to iron deficiency, therefore indirectly proportional to amount of iron in the body

How are sTfRs lost from cell surface?

Via proteolysis

What condition would you expect to see increased sTfR?

Iron deficient anemia

What is the equation to find sTfR-F index?

(sTfR) / log ferritin

What sTfR-F index would indicate iron deficient anemia?

Over 1.8

What is RPI?

Reticulocyte production index

What RPI value denotes ineffective hematopoiesis?

Below 2

What is the main regulator of the iron level in the body?

Hepcidin

What is hepcidin, and what does it do?

It's an acute phase reactant from the liver that decreases iron absorbance and blocks its export from cells by degrading ferroportin

What could increase hepcidin production?

An increase in iron or stress (since it is an acute phase reactant)

Which cells does hepcidin work on?

Macrophages, enterocytes, hepatocytes

What is the relationship between hepcidin and total iron demand?

Inversely proportional

Which transferrin receptor has greater affinity for iron?

TfR1

Which transferrin receptor initiates the production of hepcidin?

TfR2 (with interaction from HFE)

What are characteristic symptoms of iron deficiency anemia?

Koilonychia (spooning nails), angular stomatitis (cracked corners of mouth), cheilitis (inflamed lips), pica (inappropriate appetites--not those)

What symptom is associated with hemochromatosis?

Bronzed skin/pigmentation

What symptom is associated with lead poisoning?

Lead line in gums

Which transferrin receptor will most likely bind iron if there is an increased concentration of it?

TfR 2 for the purpose of storing it

How is HFE affected by an increase in iron concentration?

It is displaced from TfR1 to TfR2

What is holo-Tf and what does it bind to?

Diferric transferrin, binds to transferrin receptors 1 and 2 (TfR1 and TfR2)

When is an increase in matriptase-2 (MT-2) seen on hepatocytes?

Iron deficiency

What initiates the inflammation induced pathway of hepcidin production?

IL-6 binding to the IL-6 receptor

What does IL-6 binding to IL-6 receptor on a cell induce?

Activation of JAK-STAT3 pathway for producing hepcidin

What function does matriptase-2 perform?

It degrades HJV for the purpose of inhibiting hepcidin production

What does the HFE/TfR2/holoTf complex interact with?

Bone morphogenetic protein (BMP) receptor, its ligand BMP6, and the HJV coreceptor

What does the SMAD pathway do?

Signals up-regulation of hepcidin

What is the most frequent anemia witnessed among hospital patients?

Anemia of chronic disease

What is the most common anemia witnessed worldwide?

Iron deficient anemia

What is secondary hemachromatosis referred to as?

Hemosiderosis

Which gene is affected in hemochromatosis?

HFE gene, mutations C282Y and H63D

What is the hallmark of lead poisoning?

Basophilic stippling
Ringed sideroblasts in children

How does alcohol affect iron absorption?

It increases absorption

Where is the iron in hemosiderosis?

Iron accumulation in macrophages of RES

What is the mechanism behind hemochromatosis?

Increased iron absorption from gut

What is the prognosis for a patient with sideroblastic anemia?

Potentially fatal; succumbing to iron overload

What cytokines are produced by monocytes in anemias of chronic disease?

IL-6, IL-1, IL-10, TNF-alpha

What cytokines are produced by lymphocytes in anemias of chronic disease?

IFN-gamma

What does IL-6 do in anemias of chronic disease?

Increases liver production of acute phase reactant proteins hepcidin and apoferritin

What does IL-1 do in anemias of chronic disease?

Increases production of acute phase reactant proteins and decreases EPO production and erythropoiesis

What does TNF-alpha do in anemias of chronic disease?

Increases phagocytosis (leaking to increased RBC breakdown) and decreases EPO production and erythropoiesis

What does hepcidin do in anemias of chronic disease?

Inhibits ferroportin (release channel for Fe), decreases Fe absorption and erythropoiesis

What does IFN-gamma do in anemias of chronic disease?

Increases entry of iron via divalent metal transporters, and decreases EPO production and erythropoiesis

What are porphyrias due to?

Abnormal heme synthesis

Where can heme precursors build up in porphyrias?

Bone marrow - erythropoietic
Liver - hepatic

What are common symptoms associated with congenital erythropoietic porphyria?

Photocutaneous lesions, mild or severe hemolytic anemia