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85 Cards in this Set
- Front
- Back
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Human body contains about __ to ___ g of iron |
2 to 4 |
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>____% found in hemoglobin
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65 |
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Up to ____% found in myoglobin |
10 |
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1-5% is found within ________ |
enzymes |
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where is the rest of iron? |
rest is in blood or in storage |
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Iron is found in the body as ______ ____ (Fe3+) or _________ _____ (Fe2+) |
Ferric iron and ferrous iron |
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Almost always bound in the body through redox potential and ________ ______ |
bacterial growth |
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Iron UL for most groups? |
40 mg/d or 45 mg/d |
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0-6 months Iron AI and elaborate on the iron stores |
0.27mg -iron stores in the body from the mother and placenta sustain the infant |
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7-12 months DRI amount and 2 key points |
11mg -stores from birth become depleted -iron fortified cereals are introduced |
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DRI amount: 1-3 years ____ mg DRI amount: 4-8 years ____ mg why is iron important at this stage? |
7 10 iron is required to support rapid growth |
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DRI amount for pregnancy and 3 points on the importance of it |
27 mg -placentage contains ~150mg of iron -Fe intake must support increase in maternal blood volume -must also support growth of fetus |
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DRI amount for lactation and 2 points on the importance of it |
9-10 mg -milk is a poor source of iron -lactational amenorrhea reduces requirements for iron |
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DRI amount for adult women and 2 points on importance of it |
18 mg -supports menstruation -iron loss 4-30 mg/month |
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DRI amount for adult men? |
8 mg |
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What are the 2 sources of iron? |
1) Animal Sources 2) Plant Sources |
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What about iron in animal sources? |
-animal sources contain both heme and non-heme iron -50-60% of iron in fish, meat and poultry is heme iron -heme iron can be absorbed 2x more efficiently than non-heme |
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What are some examples of animal sources? |
canned clams 45 mg 1 cup raw oysters 13-16 mg |
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2 key points about iron in plant sources
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-plant sources contain only non-heme iron -grains typically fortified with iron (-flour = 4.4mg/100g / cereal 8 to 100% daily value) |
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list some examples of iron found in plant sources |
navy beans 4.5 mg spinach 3.2 mg baked potato with skin 2.5 mg |
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iron absorption efficiency ranges from ______% |
2-35% |
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What are the 4 enhances of iron absorption form the gut? |
1. sugars 2. acids 3. meal, poultry, fish (protein) 4. mucin |
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explain how sugars enhance iron absorption in the gut |
sugars (especially fructose & sorbitol) -chelating agents or ligands |
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explain how and which 4 acids enhance iron absorption in the gut |
Acids - ascorbic, citric, lactic and tartaric -can reduce Fe3+ and Fe2+ and can chelate F2+ iron -keeps it soluble & therefore improves absorption |
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explain how meat,poultry, fish can enhance iron absorption in the gut |
-stimulates gastric/intestinal secretion -contains heme iron -amino acid products of protein hydrolysis are acidic -cysteine & histidine may acts as weak chelators to facilitate iron absorption |
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explain how mucin enhance iron absorption in the gut |
-chelates multiple ferric iron atoms at an acidic pH -maintains Fe3+ solubility in small intestine |
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What are the 6 inhibitors of iron absorption from the gut? |
1) polyphenols 2) oxalate 3) phytate 4) high levels of dietary calcium & phosphorus 5) high levels of deitary Zn, Manganese, Nickel 6) antacids & proton pump inhibitors |
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how do polyphenols inhibit iron absorption |
-sources of tea & coffee -contains: tannins, epigallocatechin-gallate also known as EGCG which is antioxidant -60% decrease in absorption when consumed in meal -40% decrease with coffee consumption immediately after meal |
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how does oxalate inhibit iron absorption |
bound mineral compexes are insoluble & poorly absorbed |
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how does phytate inhibit iron absorption |
-bind positively charged metals and cations such as Zn & Fe -yeast contains phytase but can only efficiently hydrolyze non-complexed phytate |
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how do high levels of dietary Ca2+ & Phophorus inhibit iron absorption |
-calcium/milk ingestion can decrease Fe absorption by 70% through: 1) chelates non-heme iron in gut into F2:Ca:PO4 -forms insoluble complex -unabsorbed -lost in feces 2) inhibits both heme & non-heme Fe absorption -heme iron is soluble -heme iron does not bind Ca2+ in the SI lumen -thus must be an effect within enterocytes causes ferroportin transporter to transiently move from basolateral membrane to cytosol |
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how do high levels of dietary Zn, Manganese, Nickel inhibit iron absorption |
-competes for divalent mineral transporter 1 (DMT1) |
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how do antacids & proton pump inhibitors inhibit iron absorption |
-can contain a lot of Ca2+ or Al3+ -tend to increase pH of intestinal contents |
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Describe the four steps in heme iron digestion and absorption |
1) hemoglobin/myoglobin is hydrolyzed by HCI and proteases to release 4 heme units + 4 globin units 2) heme remains soluble 3) Heme is absorbed intact into enterocytes by a specific transport protein (heme carrier protein 1) 4) once in enterocyte, heme is hydrolyzed by heme oxygenase, releasing ferrous ion (Fe2+) |
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Describe the four steps in non-heme iron digestion and absorption |
Non-heme iron digestion & absorption 1) HCI and proteases in stomach and proteases in small intestine aid in release of nonheme iron from food 2) Fe3+ is the main form released 3) it is soluble in the acidic environment of the stomach and can be converted to Fe2+ 3) However in more akaline environment of the SI -Fe3+ complexes to form insoluble Fe(OH)3 -Fe(OH)3 aggregates & precipitates |
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How does non-heme iron digestion and absorption occur through Fe3+ Iron absorption? |
-Fe3+ (ferric iron): mechanism of absorption is not clear -may be faciliated by organic compounds called ligands and chelators -these bind, sequester and solubilize ferric iron -can facilitate or inhibit iron absorption -integrin - membrane protein thought to facilitate Fe3+ absorption into enterocytes |
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What is the difference between chelators that bind to iron strongly and loosely? |
- chelators that bind iron strongly make it insoluble then they only serve to increase iron excretion in feces - chelators that bind iron loosely make it soluble - help to deliver it to the brush border membrane |
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How does non-heme iron digestion and absorption occur through Fe2+ Iron absorption? |
- ferrorous iron (Fe2+) is fairly soluble at alkaline pH - ferrireductases (Dcytb*) are present on the BBM of enterocytes - increases formation of more soluble Fe2+ iron - increases absorption - Fe2+ can be absorted into enterocytes by DMT1 DMT1 = divalent cation transporter or divalent metal ion transporter or divalent mineral transporter also transports Zn, Mn, Cu, Ni, Pb DMT1 synthesis is upregulated by low iron status |
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4 steps on digestion + absorption of iron? |
1. hemoglobin is hydrolyzed in stomach and small intestine to yield heme that remains soluble 2. heme is absorbed intact into enterocytes by HCP1 (heme carrier protein 1) -heme is lysed to protoporphrin ring & Fe2+ 3. bound nonheme ferrous iron is released from foods by action of HCI and proteases in stomach and enzymes in small intestine a) iron can bind to ligand or chelator if strongly bound, then may be excreted b) if it is in Fe3+ form, it may precipitate from solution and will be lost in feces c) or iron can bind to ligand or chelator, loosely bound, then it can be absorbed 4. a) Fe2+ from food is absorbed by DMT1 b) Fe3+ is fairly soluble in low pH of stomach, but insoluble at higher pH -only minimally absorbed as Fe3+ -reduction to Fe2+ by Vitamin c-dependent ferrireductases such as Dcytb* allow for greater absorption |
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what is the role of Iron in enterocytes as carrier proteins |
-essentially all iron is bound to amino acids (e.g. cysteine and histidine) or to binding poteins -provides a source of iron for enterocytes |
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what is the role of Iron in enterocytes in storage? (in terms of ferritin) |
Ferritin -has ferroxidase activity: converts Fe+ to Fe3+ for storage - can store up to 4500 Fe atoms - must be reduced again to release from ferritin - enterocytes are sloughed off from lumen within 2-3days and iron stored in ferritin is lost |
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what is the role of Iron in enterocytes in storage? (in terms of Hemosiderin) |
Hemosiderin -may be 50% Fe -seen predominantly at higher conc of iron |
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what is the role of Iron in enterocytes in the transport across the BLM? (in terms of ferroportin (FP) ) BLM = basolateral membrane |
Ferroportin (Fp) -also called MTP1 (metal transporter protein 1) or Ireg1 -located on BLM -transports Fe2+ across enterocyte basolateral membrane into blood -transport is coupled with Fe2+ oxidation to Fe3+ by copper-containing protein called hephaestin |
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what is the role of Iron in enterocytes in the transport across the BLM? (in terms of Hephaestin ) |
- Fe2+ is hte major "non-storage" form of iron in enterocytes - Hephaestin oxidizes Fe2+ to Fe3+ using Cu2+ - Fe3+ binds the blood transport protein transferrin |
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What is the role of transferrin in blood transport |
Transferrin -major iron transport protein in blood -binds & transports up to 2 iron atoms in blood (differric transferrin vs monoferric transferrin) -transports only Fe3+ -uptake is via the transferrin receptor and endocytosis |
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how does hepcidin signaling affect regulation of iron efflux from enterocytes?
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-protein synthesized & released by liver when blood iron levels are high -degrades ferroportin on enterocytes -blocks release of Fe from enterocytes - causes Fe to remain trapped in enterocytes that are sloughed off -therefore decease absorption/increases loss |
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how does low levels of Fe in enterocytes affect regulation of iron absorption from lumen? |
i) increases DMT1 ii) increases ferrireductase iii) decreases ferritin |
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how do iron response elements affect regulation of iron uptake by enterocytes? |
- iron response element binding protein (IRE-BP) responds to cell's iron status - only functional when [Fe] decreases - increases cellular [Fe] - IRE-BP binds 4 Fe atoms, and it functions in the TCA cycle but does not bind IRE - decreases cellular [Fe] - IRE-BP is only partially bound with 3 or fewer Fe atoms and it binds to IRE on mRNA - IRE-BP responds to cell's iron status -can repress or enhance translation of mRNA |
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depending on an enhancer or repressor, how does it affect mRNA stability?
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enhancer - increases mRNA stability: increase protein repressor - decreases mRNA stability: decrease protein large dose of iron increaes Fe content of enterocytes |
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what is the role of 3Fe: IRE-BP (active when iron levels are low) |
Enhances translation of: 1. Transferrin increases -increases transport capacity of blood -increases absorption of Fe from enterocytes 2. DMT1 increase - increases intestinal absorption of Fe2+ 3. Dcytb increase - increases Fe2+ form in intestinal contents - improves iron absorption |
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what is the role of 4Fe: IRE-BP (active when iron levels are high) |
Loss of enhanced translation of: 1. Transferrin decreases -decreased transport capacity of blood -decreased absorption of Fe from enterocytes 2. DMT1 decreases -decreased intestinal absorption of Fe2+ 3. Dcytb decreases -decreased Fe2+ form in intestinal contents -poorer iron absorption |
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what are the 3 summarized points on rat case studies? |
1. rats were given a large oral dose of Fe (10Mg) 2. mRNA levels of IRE-BP responsive proteins was measured 3. IRE-BP is inactive when iron stores or dietary iron levels are high |
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What can you conclude about the case study on rats? |
-large dose of iron increases Fe content of enterocytes -loss of enhancing effect on iron responsive mRNAs: decrease in Dcytb & DMT1 mRNA |
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What are the 5 functions of iron? |
1. blood O2 transport 2. myoglobin 3. electron transport 4. drug metabolism 5. non-heme fe-dependent oxygenases, peroxidases and hydroxylases |
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Describe the Blood O2 transport function of iron |
Blood O2 Transport of Iron - 98.5% of total O2 in blood is bond to hemoglobin -hemoglobin is polypeptide consisting of 4 subunits of heme bound to the polypeptide molecule globin -Fe is found within the heme porphyrin ring -Fe within heme can loosely bind 1 molecule of O2 -Eeach RBC contains millions of Fe atoms -RBC contain about 2/3 of body Fe |
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Describe the myoglobin function of iron |
Myoglobin - skeletal muscle cystoplasmic protein containing heme iron -facilitates rate of diffusion of O2 from capillaries to mitochondria to fuel electron transport |
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Describe the electron transport function of iron |
Electron transport - heme-containing cytochromes and non-heme iron sulfur - uses the different redox states of iron - Fe of the reduced cythochrome becoems oxidized from ferrous iron to ferrir iron, transferring an electron to next cytochrome that becomes reduced |
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Describe the drug metabolism function of iron |
Drug Metabolism -cytochrome P450 family of enzymes contain Fe - metabolize zenobiotics including caffeine, aspirin and carcinogenic heterocyclic amines in grilled meat |
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Describe the non-heme Fe-dependent oxygenases, peroxidases and hydroxylases function of iron |
Non-heme Fe-dependent oxygenases, peroxidases and hydroxylases Catalase -catalyzes breakdown of hydrogen peroxide to H2O and O2 -host of other enzymes invovled in synthesis and degradation reactions involving amino acids, nucleic acids and organic molecules |
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Where does iron deficiency anemia occur the most (geographically) ? |
Africa and south asian countries |
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____ billion people suffering from iron deficiency
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1-5 |
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up to ____ billion are anemic |
2 |
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_________ _______ is the most common form in iron deficiency |
microcrytic anemia |
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iron deficiency in developed worlds is due to ___________ ______ ______, especially in ______________ women |
inadequate iron intake / menstruating |
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iron deficiency in developing worlds is due to ________ and insufficient ________ _____ |
parasites / dietary intakes |
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What 4 groups of people are most common to have iron deficiency? |
1. infants and young children (6months - 4 years 2. adolescents during early rapid growth spurt 3. females during childbearing years due to menstrual iron losses 4. pregnant women |
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Explain how infants and young children are vulnerable to iron deficiency |
-low iron content of milk -rapid growth rate -insufficient body reserves -early umbilical cord clamping 80 ml of blood transferred in 1st min after birth -provides 40-50 mg/kg body weight of additional iron -newborn is born w/ 75mg/kg body weight |
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Explain how adolescents are vulnerable to iron deficiency |
-expansion of blood volume, skeletal muscle mass and liver volume + enzymes |
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Explain how pregnant women are vulnerable to iron deficiency |
-expanding blood volume -increased demands of fetus and placenta -blood losses incurred in childbirth - increase risk of hemorrhage & sepsis during childbirth - implicated in 20% of maternal deaths - 2X risk of death with moderate anemia -anemic mothers transfer less iron to offspring -increased risk of premature, low birth weight babies with compromised immunity |
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Iron deficiency symptoms? |
fatigue, weakness, pallor and cold intolerance |
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symptoms in children? |
-behavioural disturbances -impaired cognitive performance -irreversible impairment of learning ability |
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neurological symptoms in growth and development when one has iron deficiency - WHY? |
iron is required for enzymes involved in metabolism of phenylalanine, tyrosine and tryptophan |
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how does iron deficiency affect Lethargy? |
Lethargy -iron is required for hemoglobin synthesis, O2 transport and therefore energy metabolism -energy is required to focus & learn |
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how does iron deficiency affect Phenlylanine hydroxylase (PAH) |
-catalyzes 1st step in catabolism of phenylalanine -mutations in PAH cause phenylketonuria -excess phenylalainine in blood prevents uptake of other large, neutral AAs across BBB -prevents normal brain development -causes brain damange + seizures |
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how does iron deficiency affect Tryosin Hydroxylase? |
-catalyzes 1st step in synthesis of neurotransmitter dopamine -dopamine is precursor for syntehsis of NE/E -iron deficiency anmemia in infancy is associated with permanat reduction in # of dopamine receptors in brain |
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how does iron deficiency affect Tryptophan? |
Tryptophan hydroxylase -catalyzes rate-limiting step in synthesis of neurotransmitter serotonin -iron deficiency anemia in infancy is associated with permanent reduce in brain serotonin levels |
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what are 3 kinds of iron supplements? |
1. over the counter 2. liquid 3. sprinkles |
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whatis the result of Lead (Pb) interaction with iron? |
-decrease absorption of lead occurs in iron deficiency (DMT1) -lead inhibits enzymes involved in heme synthesis -lead poisoning is therefore associated with anemia |
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4 sites of excretion for iron |
1) Gi tract - 0.6 mg/day 2) skin - 0.2-0.3 mg/day 3) urine - 0.08 mg/day 4) menstrual losses - 18mg - 40mg |
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what is the total loss of iron in a day? |
1.38 - 2.38 mg/d |
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What is hemochromatosis? |
iron toxicity -occurs in young children following accidental Fe overdose -also occurs in adults with genetic mutations causing 2-fold increase in iron absorption -includes mutations in hepcidin & other genes -affects 1 million americans |
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what occurs in hemochromatosis? |
-causes deposition of Fe in joints + tissues -especially in heart, liver, pancreas -causes extensive organ damage & failure |
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what are symptoms of hemochromatosis? |
diabetes, depression, cardiomyopathy, arthritis, testicular failure, joint & bone pain |
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men vs women in hemochromatosis? |
menstruation is protective in women |
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possible onset age in men and women? |
Men: 20-30 Women: 10-15 yrs after |
