Term
Robbins Table 14-6: G6PD deficiency - how it looks in histo slide
what causes the episodic hemolysis in patients with G6PD deficiency?
What signs do you see 2-3 days after oxidant exposure in these pts? |
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Definition
red cells have precipitates of denatured globin (Heinz bodies) revealed by supravital staining
splenic macrophages pick out inclusions, leave "bit marks" on RBC
hemolysis caused by events that cause oxidative stress (infections, drugs, foods). Oxidants cause intra- and extravascular hemolysis in pts with G6PD def.
acute intravascular hemolysis, anemia, hemoglobinemia, hemoglobinuria
-episode is self-limiting; recovery is marked by reticulocytosis
-features related to chronic hemolysis (splenomegaly, cholelithiasis) are absent |
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Term
| Iron distribution in adults |
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Definition
men - total 3450 mg, Hb 2100, Mb 300, 1000 storage (ferritin, hemosiderin)
women - total 2450 mg, 1750 Hb, 250 Mb, 400 storage |
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Term
| Compare total iron content in men, women, children |
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Definition
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Term
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Definition
Iron in to plasma ion pool: 1-2 mg/day
circulation through liver
circulation through blood: 20 mg/day
-erythrocyte production in bone marrow
-RBC
-erythrocyte destruction by macrophages
iron out from ion pool: 1-2 mg/day |
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Term
Robbins figure 14-22
- describe the mechanisms and regulations involved in intestinal cell iron absorption |
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Definition
Iron balance is maintained by regulating the absorption of dietary iron in the duodenum
Duodenal EC take up heme and nonheme iron
-when storage sites of body are full of iron and erythropoiesis is normal, plasma *hepcidin* is high --> down-regulation of ferroportin & trapping of absorbed iron, lost when EC are shed into gut
-when stores are low or erythropoiesis is stimulated, hepcidin levels fall, ferriportin activity increases --> more absorbed iron is transferred to transferrin
-hepcidin regulates iron absorption! (inhibits iron transfer from RBC to plasma by binding to and degrading ferriportin) |
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Term
| Describe the pathway of iron absorption, transportation, storage and utilization of iron |
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Definition
Iron is absorbed by duodenal EC
-nonheme (Fe3+) has to be reduced to +2 by ferrireductases
-heme (Fe2+) is transported across membrane by DMT1
-nonheme and heme Fe++ enter a common pool
Iron is then transported to blood or stored as mucosal iron
-iron destined for circulation is transported by fereriportin (coupled to oxidation of Fe++ -> Fe3+
-Fe3+ binds to transferrin, delivered to RBC precursors in BM |
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Term
| Define ferritin and hemosiderin as storage proteins for iron |
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Definition
Ferritin - plasma storage, ubiquitous protein-iron complex. Derived largely from storage pool of body iron, levels correlate with body iron stores
-ferritin iron is turned into either transferrin or hemosiderin
Hemosiderin - found within cells; excess iron storage |
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Term
| Define the relationship between body stores of iron and circulating plasma ferritin |
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Definition
| They correlate! If body stores are high, so are ferritin levels |
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Term
| Robbins figure 14-21 - Iron metabolism |
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Definition
Iron absorbed from gut is bound to plasma transferrin
delivered to developing RBC, incorporated into Hb
Mature RBC are released into circulation
After 120 days, ingested by macrophages (esp spleen, liver, BM)
Iron is extracted from Hb, recycled to plasma transferrin
Iron absorbed from gut is balanced by losses in shed keratinocytes, enterocytes, and (women) endometrium |
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Term
| Define iron metabolism, specifically how iron is recycled |
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Definition
Iron is recycled extensively b/t the functional and storage pools
Transported in plasma by transferrin
Recycled in the spleen
-extravascular hemolysis
Lost (not reutilized)
-feces, urine, sweat, intravascular hemolysis |
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Term
| describe the pathway of heme degradation |
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Definition
After 120 days, RBC are phagocytosed
Globin is released, converted to AA
Heme is degraded to bilirubin, which is excreted in the bile
Heme is oxidized, cleaved to make CO and biliverdin
Iron is released, oxidized, and returned by transferrin to the body iron stores
Biliverdin is reduced to make bilirubin, which is carried by albumin to the liver
In the liver, bilirubin reacts with UDP-glucuronate to form bilirubin monoglucuronide, which is converted to diglucuronide
Formation of diglucuronide i/c the solubility of the pigment, bilirubin diglucuronide is secreted into the bile
Bacteria in intestine convert bilirubin to urobilins and stercobilins |
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Term
| Describe the pathways of heme biosynthesis |
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Definition
Heme regulates its own production by repressing the synthesis of delta-ALA synthase in the liver
Two molecules of delta-ALA form pyrrole porphobilinogen
Four porphobilinogens form the first in a series of porphyrins
The porphyrins are altered by decarboxylation and oxidation
Protoporphyrin IX binds Fe++, forming *heme*
-dietary iron is transported via transferrin, stroed as ferritin in the BM
-vit C increases iron uptake from intestinal tract
-excess iron is stored as hemosiderin
Erythropoietin induces heme synthesis in BM
Heme stimulates the synthesis of globin by maintaining the translational initiation complex on the ribosome in the active state
Defects in biosynthesis of heme result in porphyrias |
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Term
| Correlate the relationship b/t the deficiency of specific enzymes and porphyria |
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Definition
delta-ALA porphyria - d-ALA def
Acute intermittnet porphyria - hydroxymethylbilane synthase def
Congenital erythropoietic porphyria - uroporphyrinogen III cosynthase def
Porphyria cutanea tarda - uroporphyrinogen decarboxylase def
Hereditary coproporphyria - coproporphyrinogen oxidase def
Variegate porphyria - protoporphyrinogen oxidase def
Erythropoietic protoporphyria - ferrochelatase def |
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Term
Describe the underlying mechanisms of iron deficiency, list 4 major causes for iron deficiency
what type of anemia does iron deficiency produce? |
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Definition
1. dietary lack
2. impaired absorption
-sprue, steatorrhea, chronic diarrhea, gastrectomy
3. increased requirement
-growing infants/kids/teens, premenopausal women
4. chronic blood loss
-external hemorrhage, bleeding into *GI*/urinary/genital tracts
hypochromic microcytic anemia |
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Term
| Describe the most common cause of iron deficiency in the western world |
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Definition
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Term
| Describe the peripheral blood cell appearance in iron deficiency |
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Definition
| hypochromic, microcytic RBC |
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Term
| Describe the bone marrow appearance in iron deficiency, specifically the assessment of iron stores in the bone marrow |
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Definition
mild-mod i/c in erythroid progenitors
disappearance of stainable iron from macrophages (Prussian blue stain)
hemosiderin (blue) particles are absent
<10% of RBC granules contain siderotic granules
low Hb, Hct, ferritin, transferrin saturation, hepcidin
high TIBC, transferrin |
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Term
Serum iron
Serum ferritin
Total plasma iron binding level
Transferrin saturation |
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Definition
Serum ferritin is low in iron def, high in inflammation and when there's damage to iron rich tissues (e.g. liver, hepatitis)
TIBC reflects Fe binding capacity of transferrin - increases with iron deficiency
% (transferrin) saturation - N 33%, d/c to 16% in iron def
-when low, is the most specific indicator of Fe def
<5% almost always indicates Fe def
>12% make dx unlikely |
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