Blood 2 Flashcards
Iron metabolism
- Absorption: Fe2+ absorbed thru intestinal mucosa
- Most iron is recycled from RBCs (not diet)
- Vit c helps absorption
- Oxidation: ceruloplasmin oxidizes Fe2+ to Fe3+ (ferrous to ferric)
- Transport: tranferrin binds Fe3+ and transports it to BM primarily (liver + spleen too)
- Uptake: Iron delivered to tissues w transferrin receptors
- Incorporation: In RBCs, Fe3+ reduced and incorporated into heme, then into hemoglobin
- Storage: ferritin binds + stores extra iron (BM + liver)
Hemoglobin synthesis
- Fe uptake thru tranferrin receptor mediated endocytosis
- Transferrin:iron binds to transferrin receptor, endocytosis
- In cytosol Fe3+ dissociates from transferrin
- Reduced by ferrireductase for entry into mitochondrion
- Or stored as Fe3+ by ferritin in the cytosol
Rate limiting step: glycine + B6 + succinyl CoA -> SALA(?)
- heme joins w polypeptide to form hemoglobin chain (a or b)
- Adult hemoglobin: HbA composed of 4 HG chains, 2 a and 2 b each w a heme group
- each molecule can bind 4 O2 molecules, one O2 to the ferrous iron in each heme group
2,3-DPG
decreases binding affinity of O2 to hemoglobin -> oxygen delivery
Decr pH also helps w oxygen off-loading
Fetal hemoglobin (HbF)
a2g2`
HbA2
a2d2
off-loading of oxygen
Lower O2 concentration -> less binding affinity of heme groups to O2
How does high latitude hypoxia impact blood composition?
- Low o2 delivery to kidney, HIF-alpha and -beta triggers epo synth and secretion
- EPO acts at BM promoting erythropoiesis, incr in RBC count and hematocrit
- HIF-1a and b stimulates angiogenesis (formation of new blood vessels), transferrin receptor synthesis (facilitating cellular iron uptake), and inhibits hepcidin
benefits of live high train low?
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Hemoglobin switching
b incr and gamma decr after birth
Embryo:
Fetus: F (alpha2gamma2)
Adult: F, A2 (alpha2delta2), A (alpha2beta2)
PICS of
Porphyrias
Disorder of heme synthesis -> abnormal build up of porphyrin precursors or porphyrins in BM and/or liver (erythropoietic or hepatic)
- Heme pathway has 8 enzymes, absence of any can lead to disease
(porphyrin = part of heme that binds iron)
* not enough functional RBCs
thalassemias
Inherited disorder resulting in reduced/no synthesis of one or more globin chains
- disordered a chain synth = a-thalassemia (affects fetus)
- disordered b chain synth = b-thalassemia (affects adult)
both alter a:b chain ratio and reduce o2 binding to hemoglobin
tetramer of 4 alpha chains could still work, but not as efficient as ab chains
If there is issue w beta chains, gamma chains could be upregulated to have equal amts as a chains
sickle cell disease
results from defective b-globin gene
- when oxygen is bound, rbcs are normal shaped
- when oxygen dissociates: within beta sickle cells, hemoglobins stack, leading to blockage of microcirculation
In equatorial africa, this is common, protects against malaria, disrupotion in actin in sickle cells, malaria doesn’t thrive
Erythrocyte breakdown
Lifespan: 120 days
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Hemoglobin metabolism
after breakdown of hemoglobin: globins -> AAs -> AA pool for protein synth
Heme:
1. releases fe2+, oxidized to fe3+,
2.
albumin transports plasma bilirubin to liver, taken up and conjugates w glucuronic acid -> forms bilirubin glucuronide
BG secreted from bile duct to small intestin (secretion)
50% conj bilirubin is converted to urobilin in intestine, then:
1. recycled in liver, re-excreted
2. reabs into portal circulation and subsequently transported to kidneys for excretion in urine (gives pee yellow colour)
3. converted to ster-something in feces (give poo brown colour)
