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?
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?
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?
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?
what will happen to the iron absorption when you have alkaline pH?
what will happen to iron absorption when you have gastrectomy?
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?
what will happen to the absorption if iron when you have ineffective erythropoiesis?
what will happen if you eat ascorbic acid, citric acid, AA and sugar?
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?
which type of storage pool surrounds the core of the ferric hydroxyphosphate and it is readily available for metabolism?
what is the type of storage pool that is precipitated and partially digested-?
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?
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?
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?
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?
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?
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?
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?
what is the RDW in iron deficiency?
pencil cells and fragmented RBCs
what is the amount of reticulocyte count?
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?
what is the term for accumulation of iron within parenchymal cells?
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?
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?