Ch4 RBC 2

What function(s) do erythrocytes perform in the blood?

carry o2 to tissues and transport CO2 away from tissues

act as a hydrogen ion (H+) buffer

Define oxygen affinity.

characterized by P50

• high affinity prefererd for oxygen rich tissues

• low affinity preferred for oxygen poor tissues

What factors affect hemoglobin’s oxygen affinity

• allosteric protein: binding of one oxygen molecule increases affinity of other sites

• CO (contributes to pathology of CO posioning

• 2,3-DPG (decreases Hb O2 affinity inside RBCs)

Heme

• contains porphyrin ring

• Iron molecule

  • O2 binding site

Heme can contain how many O2?

4

Increase in free heme?

increase in globulin monomer synthesis and inhibits iron uptake

decrease in free heme

decrease in monomer formation

Porphyrin + Iron =

heme

Fe2+ when

unbound

Fe3+ when

binding to oxygen

One hemaglobin

4 globin chains + 4 heme groups

List three ways that oxidation can damage erythrocytes.

• hemichrome and band 3 cluster → eaten by macrophage

• oxidation of globin results in heinz → RBC deformability

• oxidation of heme → methemoglobin

How do erythrocytes prevent this?

RBC anti-oxidant system

• cytochrome b5 reductase (methemoglobin reductase) using NADH as the electron donor

• redcued glutathione (GSH)

GSH

• non-enzymatic free radical scavenger

• when it becomes oxidized, it’s reduced back to GSH by NADPH dependant glutathnione reductase (GR)

How does erythrocyte metabolism differ from nucleated cells?

anaerobic glycolysis (embden-meyerhof pathway)

• due to not having a mitochondria or nucleus

RBC need

ATP

How do erythrocytes generate ATP?

• use glucose for energy

  • 90-95% glycolysis (EM pathway) (ATP)

  • 5-10% PPP (NADPH)

• DPG cycle (used to decrease Hb affinity so more O2 can unload at tissue)

What effect does hepcidin have on iron absorption?

• systemic control of iron metabolism

  • 25 aa peptide hormone, produced by hepatocytes

pentose phosphate shunt

makes NADPH, maintains glutathione and catalase in functional form

Under what condition(s) is hepcidin production increased/decreased

• too much body iron → increased production

• increased erythropoiesis or iron deficiency → decreased production

What is the transport form of iron called?

ferroportion

What is the storage form called?

ferritin

Decreased production of hepcidin in disease states →

• iron deficiency

• increased erythropoiesis

• increased iron absorption

increased production of hepcidin in disease states →

• iron overload

• decreased in iron absorption

Inflammation makes iron

harder to reach

• increased hepcidin irrespective of body iron requirements

Iron absorption is increased when

• total body iron stores are low

  • erythropoiesis is increased (increased demand)

Iron absorption is decreased when

• total body iron is high/in excess

• inflammation present

Transferrin

B-globulin with 2 FE3+ binding sites

• serum total iron binding capacity (TIBC) → measure of transferrin concentration

Ferritin

• protein shell of 24 apoferritin subunits w central core of iron atoms

• increase in apoferritin synthesis w increase in intracellular iron

Iron deficiency is normally due to

blood loss

• will cause anemia when not enough iron from normal RBC production

Inflammatory disease (pseudo-iron deficiency)

• body has iron but is not avaliable to RBC

Common causes of anemia

• anemia of inflammatory disease

• total body iron adequate but not avaliable

• trapped in tracellular stores

  • increase in hepcidin production