Iron Def and disorders of Iron Metabolism

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what is the anemia?

not dx, but basically it is because of the symptoms associated with dec in oxygen carrying capacity of the blood.

what happens to the mass of RBC number in anemia?

it decreases

what are some of the ways in which anemia can be defined?

1) to few RBC cells
2) low Hct
3) too little Hb

Describe how much Hb normal value?

12-16

what is the function of heme?

it is the prosthetic group that mediates reversible binding of oxygen by hemoglobin

what is the purpose of the globin molecule?

it protects and heme molecule.

where does heme synthesis occur?

it occurs mainly in liver and erythroid precursors.

what steps in heme biosynthesis occur in the mitochondria?

first and last two steps

where do rest of the biosynthesis of heme take placE?

in cytoplasm

where is iron absorbed?

it is absorbed in the duodenum and proximal jejunum

what is the difference between heme vs non-heme?

heme- it is derived form the animal proteins- and it is absorbed. Heme is transported across the apical embrace into the cytoplasm through heme transporters. In the cytoplasm it is metabolized to release Fe2+

non-heme- thats when the luminal non-heme iron is mostly absorbed in the Fe3+ (ferric state)- and it must be converted into Fe2+ and then transported across apical membrane by DMT!

what is the purpose of DMT

it transports Fe2+ across the membrane. The luminal is usually Fe3+ (ferric state) and it must be converted to Fe2+.

what is the purpose of duodenal cytochrome B?

it is when it takes nonheme and converts Fe3+--> Fe2+

what happens when the body has too much Iron?

that means- you have a lot of hepcidin and that will block the ferroprotein1. and Ferroprotein 1 will not be able to transfer Fe into the circulation.

what will happen to the Iron absorption when you have other materials in the food such as phosphates, oxalates, carbonates, tannates?

decrease absorption

what will happen to the iron absorption when you have alkaline pH?

decrease absorption

what will happen to iron absorption when you have gastrectomy?

decrease absorption

what are the factors that will decrease absorption of Iron?

FAG
food, alkaline pH, Gastrectomy

what will happen to the absorption if iron when you have iron deficiency?

inc absorption

what will happen to the absorption if iron when you have ineffective erythropoiesis?

inc absorption

what will happen if you eat ascorbic acid, citric acid, AA and sugar?

increase absorption

what increases the iron absorption?

CIE
vitaminC, Iron def, ineffective erythropoesis

what are the controllers of Iron metabolism?

FITT
Ferritin
Iron regulatory protein
Transferrin
Transferrin receptor

what is the role of IRP1 and IRP2?

they are cytoplasmic mRNA binding proteins and they control the expression of genes involved in iron metabolism!

when are the receptors for iron element activated?

thats when you have a lot of iron in the body- then IRP will have receptors for them and get saturated and no longer anything takes palce

what happens when iron concentrations are low?

then IRP binds to IREs in the 5' UTR of mRNA transcripts

where they repress translation (ferritin) &
they inhibit the degradation of transferrin receptor

what is the role of IRP1 and IRP2 binding to IREs?

TJ Fridays!
degradation of transferrin
Ferritin repression

where is hepcidin made and when is it released?

it is a small circulating protein synthesized in the liver and it is released from the liver in response to increased intrahepatic iron levels

what is the role of hepcidin?

it is an inhibitor of ferroportin- and it basically wants the stop of storage of ferriportin. it gets endocytosed and degraded

what is the amount of iron stores in women vs men?

women<250 mg
men- 500-2000 mg

what are the two forms in which iron are storeD?

ferritin and hemosiderin
Ferritin- thats when you have apoferritin with the surrounding core of ferric hydroxyphosphate

Hemosiderin- thats when you have precipitated aggregates of ferritin

what are the three pools associated with iron metabolism?

metabolic pool, storage pool and transit pool

what is the metabolic pool?

thats the largest pool- and it contains mostly RBCs

what is the storage pool?

thats in the form of ferritin- and it can be variable

what is the transit pool?

and it is primarily serum iron- and it can very small

what is the metabolic pool? and what does it represent.

most metabolic iron cycles through an iron conservation pathway- and it basically represents 15-20% of total body iron. so it controls how much it will take in/out?

why is Iron stored in various tissues of the body in macrophages?

because it is very toxic- so it is stored and sequestered within the macrophages of the liver, spleen, and bone marrow as well as hepatic parenchymal cells.

which type of storage pool is readily available?

ferritin

which type of storage pool surrounds the core of the ferric hydroxyphosphate and it is readily available for metabolism?

ferritin

what is the type of storage pool that is precipitated and partially digested-?

hemosiderin

what is the transit pool?

thats when you have iron that is transported in the plasma-- and it is complexed to transferrin.

The delivery of iron is also to the tissues- and it is mediated by transferrin receptor

what are the measurements associated with metabolic, storage and transit pool?

metabolic pool- blood Hb
storage pool- ferritin
Transit- serum Iron, TIBC

how do you measure the metabolic pool?

blood Hb

how do you measure the storage pool?

serum ferritin. and thats in equilibrium with the macrophages, and therefore a measure of total iron stores.

how do you measure the transit pool?

serum iron, TIBC

what is TIBC?

it is the serum iron and all the additional iron that transferrin can bind- and determines the indirect measure of transferrin

what is the TIBC approximate measure of?

transferrin

what is the % of iron bound to the transferrin?

transferrin is bound to iron- thats the % saturation of transferrin

what happens to the transferrin levels under inflammatory and malignant conditions?

it decreases, because macrophages are activated and they degrade the transferrin

what happens in hemolytic anemia- is the iron bound or unbound?

because of the hemolysis in the body- and there is a lot of iron leaking in the body- and that allows the "extra iron" to be primarily in the BOUND STATE

Is Iron primarily in bound/unbound state in iron deficiency?

unbound

Is iron primarily in bound/unbound in infection?

since there is degradation of transferrin by the macrophages due to the infection- then iron is primarily floating so it is primarily in the "unbound"state.

what is the total amount of saturation of Fe with transferrin?

35%

what is the predominant state- in bound/unbound state?

bound state- because all the other components are missing- so it has ineffective erythropoesis

what about in iron overload state?

primairly in bound state

what happens to ferritin level in inflammatory conditions?

it is elevated because ferritin is acute phase reactant

what is amount of transferrin in inflammatory conditions?

it is decreased due to macrophage degradation

what is sTfr?

serum soluble transferrin receptor
it is a reliable measure of functional iron deficiency- and it is independent of any other tests

what is the expression of Tfr depend on?

it depends on the concentration of cytosolic iron. And the mechanism is similar to that of the control of ferritin synthesis- which involves IRPs

what happens to the Tfr when the body needs iron?

it is unregulated

what happens to sTfr in iron deficiency?

upregulated

what happens to serum sTfr amount with erythropoesis?

serum sTfR is proportional to the rate of erythropoesis. The greater the amount of precursors or iron deficiencient precurosors- it would increase the serum sTfR.

what is the measure of functional iron deficiency?

sTfr- and it appears to be a reliable measure of functional iron deficiency.

what does the expression of TfR depend on?

it depends on the concentration of cytosolic iron- and it is similar in mechanism to that of control ferritin synthesis.

what is FEP?

normally- Fe2+ in mitochondria is complexed with protoporphyrin IX to form heme. When there is insufficient iron- then excess protophoryn is destained to form heme and it accumulates as FEP

what happens if there is not enough iron present?

then Fe cannot complex to form heme- and then the precursor protoporhyrin IX- accumulates as FEP

In what conditions is FEP elevated?

iron def anemia, internal block in iron utilization with ACD, Lead poisoning and sideroblastic anemia

In what conditions are FEP elevated?

Iron def anemia, conditions in which there is an internal block in iron utilization such as ACD, lead poisoning and sideroblastic anemia

what are some ways in which we can do iron stores?

serrum ferritin and prussian blue marrow stain

what is the 4+ value in Prussian blue marrow stain?

thats when we have increase amount of Iron that is stored. 2 is normal and 0 would be none.

what are some of the causes of iron deficiency?

chronic blood loss
dietary insufficiency
malabsorption
increased requirment- infants, children, adolscients and pregnant women

what are some of the causes of iron deficiency?

menstruation and GI blood loss due to gastritis, ulcer and malignancy

What are some the causes of malabsorption which leads to dietary insufficiency?

it is primarily in developing countries. However, in privileged societies- only certain groups- infants/elderly have associated problems with malabsorption

what are some of the reasons for malabsorption?

sprue, chronic diarrhea and gastrectomy

what are some of the symptoms associated with iron deficiency?

weakness and fatigue, epithelial changes in which you have cheilosis, tongue atrophy and koilonychia, depletion of iron containing enzymes, gastritis and duodenal changes, PICA and secondary sym of anemia

what is Plummer Vinson syndrome?

GEM

atrophic glossitis, Esophageal webs, Microcytic hypochromic anemia and iron def anemia

what age group does PV syndrome affect?

middle aged women

what kind of anemia do you get with hypo chromatic microcytic anemia?

iron deficiency

what is the RDW in iron deficiency?

pencil cells and fragmented RBCs

what is the amount of reticulocyte count?

decreased

what is the serum iron, ferritin, TIBC and sTfR?

decreased- serum iron and ferritin
increased- TIBC/sTfr

what happens to the hepcidin levels with iron deficiency?

it is decreased

what happens to bone marrow iron stores?

they are absent

where is Iron overload locally vs. systemically?

locally- from hemorrhage in tissue such as bruise
systemically overload- thats when you have hemosiderosis iron deposited in many organ and tissues.

what is the term for accumulation of iron in macrophages?

hemosiderosis

what is the term for accumulation of iron within parenchymal cells?

hemochromatosis

what is the etiology of Iron overload?

transfusions, hemolytic anemias (because abnormal quanities of iron are released from the erythrocytes), dietary and idiopathic

how do you diagnose Iron deficiency?

Ferritin and bone marrow biopsy and liver biopsy

what is the therapy for Iron deficiency?

chelation, phlebotomy and bone marrow transplant

what is anemia of chronic disease?

you have decreased release of iron from macrophages

what is the role of the inflammatory mediators in anemia of chronic dx?

they stimulate an increase in hepatic production of hepcidin

what happens to EPO in anemia of chronic dx?

we have inadequate EPO response

what is the reason for iron overload?

1. transfusions
2. hemolytic anemia- abnormal quanities of iron which are released from RBCs
3. dietary
4. idiopathic

what is the abnormality dealing with storage of iron?

Anemia of chronic disease

what kind of morphology do you see with anemia of chronic dx?

mild normochromic, normocytic or hypochromic microcytic anemia

what is the state of ferritin in bone marrow in anemia of CD?

you have increase serum ferritin

what is the state of serum iron anemia of CD?

decreased serum iron and TIBC

what is the state of storage iron in macrophages?

increased bone marrow storage iron
- hemosiderin in macrophages

what is the dx called in which it prevents the incorporation of iron into hemoglobin?

sideroblastic anemia

what are some of the reasons associated with sideroblastic anemia?

inherited defect in ALA synthetase or ferrochelatase

acquired- clonal disorder in which there is abnormal transport from RBC mitochondria to cytoplasm

how can you have acquired sideroblastic anemias and porphyries?

idiopathic or drug induced- anti TB drugs, chloramphenicol, chemotherapeutic drugs, alcohol or lead, or disease associated (carcinoma, leukemia, lymphoma, MM, thyroid disease)

TACCL

what are the diseases that may be associated with sideroblastic anemia?

carcinoma
leukemia
lymphoma
multiple myeloma
thyroid disease

CMLLT

what is the diagnosis of sideroblastic anemia?

ringed sideroblasts on bone marrow aspiration

peripheral blood- you will see a mixture of macrocytic and microcytic, hypo chromic, red cells

what is the treatment associated with sideroblastic anemia?

hereditary sideroblastic anemia-- you do it with Vit B6 therapy
trasfusion for palliation
allogenic bone marrow transplantation for possible cure in eligible patients

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