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 are some of the ways in which anemia can be defined?
1) to few RBC cells
2) low Hct
3) too little Hb
what is the function of heme?
it is the prosthetic group that mediates reversible binding of oxygen by hemoglobin
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 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?
what are the controllers of Iron metabolism?
Iron regulatory protein
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?
degradation of transferrin
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 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? 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 surrounds the core of the ferric hydroxyphosphate and it is readily available for metabolism?
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 storage pool?
serum ferritin. and thats in equilibrium with the macrophages, and therefore a measure of total iron stores.
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 % 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 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 predominant state- in bound/unbound state?
bound state- because all the other components are missing- so it has ineffective erythropoesis
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 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 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
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 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?
atrophic glossitis, Esophageal webs, Microcytic hypochromic anemia and iron def anemia
what is the serum iron, ferritin, TIBC and sTfR?
decreased- serum iron and ferritin
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 etiology of Iron overload?
transfusions, hemolytic anemias (because abnormal quanities of iron are released from the erythrocytes), dietary and idiopathic
what is the role of the inflammatory mediators in anemia of chronic dx?
they stimulate an increase in hepatic production of hepcidin
what is the reason for iron overload?
2. hemolytic anemia- abnormal quanities of iron which are released from RBCs
what kind of morphology do you see with anemia of chronic dx?
mild normochromic, normocytic or hypochromic microcytic anemia
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?
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)
what are the diseases that may be associated with sideroblastic anemia?
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