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Hematology - Hemaglobin (*Iron major component of Hb that is chelated by…
Hematology - Hemaglobin
*Iron
major component of Hb that is chelated by propoporphyrin to make Heme
*Iron Pathways - Absorption, Storage, transport
iron = major component of Hb that is chelated by propoporphyrin to make Heme
*Hepcidin = regulator of the 2 Iron GATES
hepcidin is made in the liver and inhibits BOTH
--> Iron Gate 1 = entry = DIVALENT DMT-1
--> Iron Gate 2 = exit "port in" to blood stream = ferroportin
Regulators of the iron Regulator Hepcidin
Increase Hepcidin - HIDE iron from bacteria and infections
--> IL6
--> high serum iron / high transferrin saturation / high TIBC
--> LPS toxins (actual infections of Gram -)
1 more item...
Gate 1 and 2 for iron = Enterocytes
think of enterocytes as the first set of gates that regulate iron entry into the body
this is very important as there is no real way to get rid of iron from the body
--> except through bleeding
Gate 1 = DMT-1
--> protein on lumen = apical side of enterocytes
--> regulates what iron can enter enterocytes
Gate 2 = Ferroportin
--> protein on blood = basolateral side of enterocytes
--> regulates what iron can enter the blood stream
--> "PORTS IN" what iron is needed in the body
*Iron overload
you need to have GATED controls for entry of iron into the body
this is very important as there is no real way to get rid of iron from the body
--> except through bleeding, etc.
*Ferrous vs Ferric forms
ferrous = Fe2+ = the "used form"
--> only way it can enter cells through the DMT
ferric = Fe3+ = "sick" form
can see here that Fe3+ is used for either
--> free transport in the gut or blood
--> storage with ferritin in BOTH enterocytes and liver
Fe3+ =
"free"
--> all iron that comes through the gut starts as "free" iron = Fe3+ state
Fe2+ =
"TWO = thru"
iron
--> whenever iron is moving THRU = 2 the inside of the cell it is in the ferrous Fe2+ form
--> hence THRU = 2+ iron is what is added to protoporphyrin to make heme
DMT-1 = DIVALENT metal transport
--> Divalent = since it co-transports DI = BOTH iron Fe2+ and H+ together
*Labs in Iron
ferritin
= iron storage
--> Fe3+ in enterocytes + liver + spleen
--> ferritin OPPOSITE to TIBC
--> TIBC regulated by ferritin levels
TIBC
= measure ~ transferrin in blood
--> OPPOSITE to ferritin
--> TIBC regulated by
ferritin
levels
serum Fe
= levels of free Fe3+ in the blood
--> transferrin + serum Fe BOTH regulated by Hepcidin levels
transferrin saturation %
= transports / binds Fe3+ in the blood
--> transferrin + serum Fe BOTH regulated by
Hepcidin
regulation (or extremes = Fe overload or depletion)
FEP
= free erythrocyte protoporphyrin
--> Hb = heme + globin
--> heme = Fe2+ + protoporphyrin
--> globin = 2alpha G + 2beta G
FEP in ACD
FEP = free erythrocyte protoporphyrin
--> Hb = heme + globin
--> heme = Fe2+ + protoporphyrin
whenever you have low Fe2+ you get high free protoporphyrin
--> thus low serum iron = high FEP
sidenote here, the TIBC is OPPOSITE to the serum iron + transferrin saturation %
--> due to the high Hepcidin upregulation
TIBC, serum Fe, transferrin saturation %
note that always have
--> ferritin OPPOSITE to TIBC
--> this is because ferritin levels determine the transferrin = TIBC levels by regulators and HFe protein
note that always have
--> serum Fe SAME as transferrin saturation %
--> makes sense as if you have high serum FE it will saturate the transferrin = TIBC more
BUT TIBC and transferrin saturation % can be either with each other or opposite
--> this is since in things like iron overload
iron overload
--> have high ferritin = storage of Fe
--> body responds by low transferrin = TIBC levels
--> but in Iron overload you have both high storage and leakage - high serum Fe levels
--> thus low TIBC but high saturation % of these TIBC
other case = ACD seen above in FEP = free erythrocyte protoporphyrin
*Iron overload Labs
transferrin + serum Fe BOTH regulated by
Hepcidin
regulation (or extremes = Fe overload or depletion)
BOTH Iron overload and Hemachromatosis have the same lab results because they are main controllers of both transferrin + serum Fe
--> and the HFe gene mutation and protein lead to iron overload
*Types of Hemoglogin
Normal endogenous forms of Hemoglobin
--> Hb A1 = A2B2 = 90% of adult
--> Hb A2 = A2D2 = 5% of adult
--> Hb F = A2G2 = 1% of adult (ALL for fetus till ~ 6 months)
--> Hb AC1 = A2B2 with carbon at N terminus = 90% of adult
Abnormal Hb types
Methemoglobin
--> Fe2+ ferrous oxidized to Fe3+ ferric
Carboxy-Hb
--> CO poisoning
--> "CO toxicity = Carboxy"
*Abnormal Hb types
Methemoglobin
--> Fe2+ ferrous oxidized to Fe3+ ferric
Carboxy-Hb
--> CO poisoning
--> "CO toxicity = Carboxy"
*Carboxy-Hb
CO poisoning
--> "CO toxicity = Carboxy"
*Methemoglobin Hb
Methemoglobin
--> Fe2+ ferrous oxidized to Fe3+ ferric
"METH heads are SICK"
--> Methemoglobin = ferric iron Fe3+
*Normal Hb types
Hb A1 = A2B2 = 90% of adult
Hb A2 = A2D2 = 5% of adult
Hb F = A2G2 = 1% of adult (ALL for fetus till ~ 6 months)
Hb AC1 = A2B2 with carbon at N terminus =
--> normal non diabetic < 6.5% of adult
*A1 = Hb
Hb A1 = A2B2 = 90% of adult
2,3-BPG
special sidepathway in RBCs
23 BPG bumps O2 out of its binding so O2 can unload at tissues
--> this is allosteric control O2
needs a postive 2-3 BPG binding pocket in the Hb structure
--> HbA1 = beta globulin gives this
--> HbF = gamma globulin has no 23 BPG binding pocket so cannot bind it
*A2 = Hb
Hb A2 = A2D2 = 5% of adul
*F = Hb
Hb F = A2G2 = 1% of adult (ALL for fetus till ~ 6 months)
--> Hb AC1 = A2B2 with carbon at N terminus = 90% of adult
NO 23 BPG binding pocket for BPG to bind
--> this is the reason why hbF has such a higher O2 binding capacity because it is unaffected by BPG
--> this also allows the transfer of O2 from HbA of mother to the HbF of the fetus at the placenta interface
*HbAC1
Hb AC1 = A2B2 with carbon at N terminus
--> normal non diabetic < 6.5% of adult
2,3-BPG
special sidepathway in RBCs
23 BPG bumps O2 out of its binding so O2 can unload at tissues
--> this is allosteric control O2
needs a postive 2-3 BPG binding pocket in the Hb structure
--> HbA1 = beta globulin gives this
--> HbF = gamma globulin has no 23 BPG binding pocket so cannot bind it
*Myoglobin
ONLY 1 subunit
used for storage of O2 in skeletal and cardiac muscle
--> thus needs to bind O2 very strongly so it can be stable while storing it in the muscle and transporting it
--> P50 = 1
it is made of either alpha or beta subunits
--> same as Hb, bu they are only SINGLE
HYPERBOLIC curve
--> vs the sigmoid of Hb
--> the sigmoid of Hb comes from heme-heme interactions that increase further binding of extra O2 once has already bound
--> since Myoglobin only has 1 site it does not have this
