Create
Learn
Share

CC March 2017 Iron-Overload Disorders

rename
echoecho's version from 2018-04-19 03:12

Section

Question Answer
Characterize what is iron-overload?1) occurs when the total body iron exceeds the normal capacity of utilization and storage 2) results in excessive iron deposits in various organs (liver, heart, pancreas and brain) 3) results in increased circulating iron
What are the symptoms of patients with iron overload limited to the reticuloendothelial macrophages?they are asymptomatic
List some symptoms that patients may present with?non-specific generalized symptoms like chronic fatigue and joint pain
What symptoms are seen at the later stages?organ-specific symptoms of chronic liver disease, diabetes, impotence, heart failure and central nervous dysfunction
In the primary care setting, what is needed to identify those who are at risk of parenchymal iron overload early before irreversible organ damage occurs?high index of suspicion
memorize
IRON HOMEOSTASIS
Question Answer
List 3 cellular functions that iron is critical in?1) erythropoiesis 2) DNA synthesis 3) energy production
Regarding normal total body iron, break down where the iron is in? What is the normal total body iron?1) hemoglobin in circulating red cells (2.5 grams) 2) iron-bound transferrin (3-7 mg) 3) nontransferrin iron (400 mg) 4) storage in liver, spleen and bone marrow (1 gram) 5) normal total body iron is about 3-4 grams
Why do adult women have less storage iron?because of the effect of 1) menses 2) pregnancies 3) lactation on iron loss and demand
The metabolism of iron is intricately regulated by balancing what?1) gastrointestinal absorption 2) loss through sweat and shedding of gastrointestinal cells (average 1-2 mg per day) 3) recycling iron from senescent red cells
What is the usual daily requirement of iron? What % is absorbed through the GI tract? What % is recaptured by recycling iron from senescent red blood cells?1) 20-25 mg 2) 10% 3) 90%
Name an acute-phase reactant produced primarily in the liver that plays an important role in iron homeostasis?HEPCIDIN
Describe what Hepcidin does?regulates intestinal iron absorption and efflux of iron into the plasma
Hepcidin is upregulated in response to what?1) increased body iron levels 2) infection 3) inflammation 4) malignancy
Hepcidin is down regulated in response to what?1) anemia 2) hypoxemia 3) iron deficiency 4) ineffective erythropoiesis
In hereditary hemochromatosis, the hepcidin level is markedly ______?decreased
Other critical _______ also enhance the uptake of iron from the gut lumen?proteins
Iron released into the circullation binds to ______, the iron-transporting protein?transferrin
In iron overload, transferrin is fully ________ and the excess iron is bound to nontransferrin protein (like citrate)?saturated
The nontransferrin-protein-bound-iron (NTBI) is not usable in ______ synthesis? What is it taken up by? What is the consequence?1) heme 2) taken up by cells such as the hepatocytes and cardiomyocytes 3) the excessive NTBI uptake is responsible for subsequent cellular damage in the involved organ
List the 10 risk factors for iron overload?1) family hx of iron overload and hereditary hemochromatosis 2) personal hx of congenital anemia (thalassemia, sickle cell disease, sideroblastic anemia, Blackfan-Diamond syndrome 3) personal hx of transfusion-dependent anemia (sickle cell anemia, thalassemia major, aplastic anemia, myelodysplastic disorders) 4) personal hx of multiple blood transfusions or parenteral iron therapy 5) personal hx of chronic renal failure 6) personal hx of chronic liver disease (alcoholic and nonalcoholic chronic liver disease and chronic hepatitis C) 7) hx of unexplained elevated liver enzymes and impotence 8) hx of porphyria cutanea tarda 9) hx of consumption of African tea with high iron content 10) hx of ingestion of known medicinal iron
memorize
DIAGNOSIS AND LABORATORY INTERPRETATION

 

History should focus on assessing risks for iron overload. What physical findings may be found? :1) may vary from a normal exam to signs of specific organ involvement 2) skin hyperpigmentation in bronze diabetes 3) testicular atrophy 4) stigmata of chronic liver disease 5) heart failure
Question Answer
List the 5 causes of iron overload?1) primary hereditary iron overload (various types of hereditary hemochromatosis) - genetic mutation results in high absorption of iron from the GI tract 2) conditions with increased iron absorption caused by ineffective erythropoiesis (most marked with thalassemia and myelodysplastic syndrome variants) (like refractory anemia with ringed sideroblasts) but also seen with sickle cell anemia, hereditary spherocytosis, porphyria cutanea tarda, chronic liver disease) 3) acquired conditions from excessive oral intake (chronic intake of iron-containing medications and products, African iron overload (increased intake plus a genetic factor) 4) acquired conditions from parenteral iron (transfusional iron over load and inadvertent iron overload from therapeutic infusion 5) perinatal iron overload (neonatal hemochromatosis, cerebrohepatorenal syndrome)
Iron overload should be confirmed by what lab testing?1) CBC 2) serum iron 3) TIBC 4) transferrin 5) transferrin iron saturation percentage 6) serum ferritin
The above tests are indirect measure of iron overload, true or false?true
The above tests are convenient and noninvasive but lack what?sensitivity and specificity
The interpretation of these tests should be taken as a total panel, understanding that what conditions may confound their values?fever, infection, acute and chronic inflammation
*** Serum _______ generally predicts total body iron storage?ferritin
*** In the absence of infection and inflammation, serum ferritin > _____ mg per mL in women and > ______ mg per mL in men and transferrin saturation > ____% in women or > ____% in men, warrant further evaluation for iron overload?200; 300; 45; 50
*** Fasting ______ _______percentage is the most sensitive screening test?transferrin saturation percentage
What is the gold standard of measuring tissue iron deposit?special staining of a liver biopsy (invasive and expensive)
List non-invasive procedures for assessing iron storage in liver , spleen pancreas, heart and brain?1) CT 2) MRI
Which imaging is especially useful and the preferred option in evaluating iron overload cardiomyopathy?MRI
When hereditary iron overload is suspected, what testing is recommended?genetic testing
What is the findings of hemoglobin, serum iron, TIBC, transferrin, transferrin iron %, serum ferritin in hereditary hemochromatosis?Hemoglobin is normal, serum iron is increased, TIBC is decreased, transferrin is decreased, transferrin iron saturation % is increase by > 45%, ferritin is increased
What is the findings of hemoglobin, serum iron, TIBC, transferrin, transferrin iron %, serum ferritin in thalassemia anemia?Hemoglobin is decreased, serum iron is increased, TIBC is decreased, transferring is decreased, transferrin iron saturation % is increased, ferritin is increased
What is the findings of hemoglobin, serum iron, TIBC, transferrin, transferrin iron %, serum ferritin in iron deficiency anemia?Hemoglobin is decreased, serum iron is decreased, TIBC is increased, transferrin is increased, transferrin iron saturation % is decreased, ferritin is decreased
What is the findings of hemoglobin, serum iron, TIBC, transferrin, transferrin iron %, serum ferritin in sideroblastic anemia?Hemoglobin is decreased, serum iron is increased, TIBC is decreased, transferrin is decreased, transferrin iron saturation % is increased, ferritin is increased
What is the findings of hemoglobin, serum iron, TIBC, transferrin, transferrin iron %, serum ferritin in anemia of chronic disease?Hemgolobin is decreased, serum iron is normal or increased, TIBC is decreased, transferrin is decreased, transferrin % is decreased, ferritin is decreased
What is the findings of hemoglobin, serum iron, TIBC, transferrin, transferrin iron %, serum ferritin in African iron overload?Hemoglobin is normal, serum iron is increased, TIBC is decreased, transferrin is decreased, transferrin iron % is increased, ferritin is increased
What is the findings of hemoglobin, serum iron, TIBC, transferrin, transferrin iron %, serum ferritin in vit B 12 deficiency anemia?Hemoglobin is decreased, serum iron is increased, TIBC is decreased, transferrin is decreased, transferrin iron saturation % is increased, ferritin is increased
memorize
TREATMENT
Question Answer
What therapy is recommended for treating all iron overload disorders (except primary overload disorders) regardless of underlying etiology?iron-chelating therapy
Currently the FDA approves what teatments?1) parenteral desferrioxamine (Desferal) given subcutaneously or by IV infusion 2) oral deferasirox (Exjade)
A recent Cochrane review concluded that desferrioxamine was effective in treating patients with ______ iron overload and deferasirox was efficacious for managing iron overload in patients with _______?transfusional; thalassemia
List the common adverse medication effects of treatment?1) irritation at the infusion site 2) visual abnormalities 3) auditory dysfunction 4) growth retardation 5) in the case of desferrioxamine, allergic reaction 6) minor GI disturbance and rash have been reported with deferasirox
*** Most patients prefer oral _______ for its convenience. Parental desferrioxamine is recommended for treating iron overload _______ or when rapid removal of iron is warranted?deferasirox; cardiomyopathy
Name the third oral agent widely used in Europe for treating iron overload?Deferiprone (Ferriprox)
Deferiprone was approved by the FDA in 2011 for treatment of what?transfusion-related iron overload based on its documented reduction of ferritin, but without controlled trials demonstrating improved clinic outcomes.
Since then Deferiprone has appeared showing an improvement in cardiac outcomes and its use in __________ associated w/ iron overload?cardiomyopathy
Is Deferiprone available as an oral agent?yes
Treatment of PRIMARY iron overload disorders such as hemochromatosis is _______ on a scheduled basis. Early intervention appears to improve outcomes and lessen complications, why?1)phlebotomy 2) early intervention before any evidence of hepatic fibrosis or cirrhosis
*** SUMMARY = Iron overload may be primary from hereditary disorders such as _________, secondary due to what? May result from hematologic disorders, such as what?1) hemochromatosis 2) transfusions from excessive iron intake or parenteral therapy 3) thalassemia with increased iron absoprtion caused by ineffective erythropoiesis
*** SUMMARY = Resultant pathologic changes to vital organs (liver and heart) and increased risk of complications like cirrhosis, cardiac failure and certain neoplasms can be reduced or prevented by early ________?intervention
*** SUMMARY = Dx is achieved by interpretation of iron-related blood analyses and can be aided by imaging studies and genetic testing, true or false?true
*** SUMMARY = Treatment for primary iron storage disorders is _______. Treatment of secondary disorders is ______ ______ therapy ?1) phlebotomy 2) iron chelation
memorize