Bhl Week 1: Intro To Erythrocyte Metabolism

Front 1

What is the lifespan of erythrocytes?

Back 1

~120 days

Front 2

List the 4 functions of erythrocytes.

Back 2

1. Gas exchange (oxygen, CO2)
2. Acid-base balance (carbonic anhydrase)
3. Clear immune complexes
4. Clear nitric oxide

Front 3

Describe the Na+ and K+ concentrations within RBCs and how this compares to plasma concentrations.

How are these intracellular concentration maintained?

Back 3

RBCs have high K+ and low Na+ intracellular concentrations

*This is opposite of plasma K+ and Na+ concentrations

*Maintained by Na-K-ATPase

Front 4

How many alpha-globin and beta-globin genes does each person normally have?

Back 4

4 alpha-globin chains (a1, a2 on each chromosome)

2 beta-globin chains

Front 5

Which chromosomes are alpha and beta-globin chains located on?

Back 5

alpha chains --> Chromosome 16

beta chains --> Chromosome 11

Front 6

How much oxygen is typically released from arterial blood into tissues?

Back 6

20 - 25%

Hb in arterial blood is about 90 - 95% saturated
Hb in mixed venous blood is about 75% saturated

Front 7

What is the normal P50?

Back 7

26 mm Hg

(P50 = partial pressure of oxygen at which Hb is 50% saturated with oxygen. *Measure of Hb-O2 affinity)

Front 8

What does a rightward shift in the O2 saturation curve imply?

Back 8

Decreased O2 affinity
Increased O2 unloading
Higher P50

Front 9

An increased O2 affinity will shift the O2 saturation curve in which direction?

Back 9

LEFT

Front 10

A lower oxygen affinity translates to a _______(higher/lower) P50.

Back 10

Higher P50.

(At a lower affinity, more oxygen is required to saturate Hb)

Front 11

How does alkalosis affect the O2 binding curve?

Back 11

Shifts it to the LEFT
(Increases O2 affinity)

Front 12

What is the primary regulator of Hb-O2 affinity?

Back 12

2,3-DPG

(Decreases O2 affinity; increases tissue oxygen supply)

Front 13

2,3-DPG stabilizes which form of Hb?

Back 13

Deoxy form

Front 14

What is the effect of acidosis, alkalosis, and temperature on O2 affinity?

Back 14

Acidosis --> Decreases affinity
Alkalosis --> Increases affinity
Increased temperature --> Decreases affinity

Front 15

What is the rate limiting step of heme synthesis?

Back 15

ALA synthetase
(glycine + succinyl-Coa ---> ALA)

Front 16

Where is porphobilinogen made within the cell?

Where is protoporphyrin IX made?

Back 16

Porphobilinogen --> Cytoplasm

Protoporphyrin IX --> Mitochondria

Front 17

Which coenzyme is required for ALA synthetase?

Back 17

Pyridoxyl 5'-PO4
(Vitamin B6)

Front 18

Which enzyme converts protoporphyrin IX to heme?

Back 18

Ferrochelatase

Front 19

Which step in heme synthesis does heme block (negative feedback inhibition)?

Back 19

ALA synthetase

Front 20

The ALA synthetase gene is on which chromosome?

Back 20

X-chromosome

Front 21

How is superoxide (O2-) converted to hydrogen peroxide?

Back 21

Superoxide dismutase

Front 22

What happens when Hb is spontaneously oxidized?

Back 22

Hemoglobin --> Methemoglobin + Superoxide
Fe2+ (ferrous) ---> Fe3+ (ferric)

*MetHb is unable to carry oxygen, and it can oxidize/damage the RBC leading to premature RBC destruction

Front 23

How is methemoglobin reduced back to hemoglobin?

Back 23

Methemoglobin reductase
(requires NADH)

Front 24

How is hydrogen peroxide reduced?

Back 24

Glutathionine reductase

Front 25

What does Methemoglobin reductase require to perform its reduction reaction?

Back 25

NADH

Front 26

What does glutathionine reductase require for its reduction reaction?

Back 26

NADPH
*Mostly comes from hexose-mannose shunt

(Reduces GSSG back to GSH)

Front 27

What is the primary source of reducing power for the RBC?

Back 27

Reduced Glutathionine (GSH)

Reduces H2O2 to H2O and becomes GSSG.

(Then re-reduced back to GSH by glutathionine reductase)

Front 28

Which enzyme performs the following reaction?

Glucose 6-PO4 + NADP+ ------> 6-Phosphogluconate + NADPH

Back 28

Glucose 6-PO4 Dehydrogenase (G6PD)

*Hexose monophosphate shunt

Front 29

What is the Rapoport-Luebering pathway?

Back 29

Pathway that occurs in RBCs to generate 2,3-DPG.

1,3-diP-glycerate ----> 2,3-DPG --> 3P-glycerate

Front 30

Why is it important for RBCs to produce NADPH?

Back 30

NADPH is used by glutathionine reductase to regenerate GSH.
GSH is necessary to reduce H2O2 to H2O.

Front 31

RBCs use NADH for which protective mechanism?

Back 31

NADH used to reduce Fe3+ (ferric) to Fe2+ (ferrous)

Front 32

How are most erythrocytes destroyed?

Back 32

They are trapped and phagocytosed by the reticuloendothelial system in the spleen --> "Extravascular hemolysis"

*A few cells are destroyed within the circulation --> "Intravascular hemolysis"

Front 33

Which portion of Hb is the source of bilirubin production?

Back 33

Protoporphyrin ring part of heme

Front 34

What is the first product of protoporphyrin breakdown?

Back 34

Biliverdin

Front 35

What form of bilirubin is "indirect"?

Back 35

Unconjugated

Front 36

What is the main source of bilirubin normally in the blood?

Back 36

Conjugated ("direct") bilirubin

(secreted in bile, reabsorbed from GI into circulatory system)

Front 37

What does an increase in unconjugated bilirubin suggest?

Back 37

An increase in bilirubin production--> increased RBC breakdown or hemolysis

Front 38

What does an increase in conjugated bilirubin suggest?

Back 38

Liver or biliary tract disease

Front 39

Describe the process of extravascular hemolysis.

Back 39

1. Hemoglobin --> globin protein + heme
2. Iron removed from heme and recycled back to bone marrow or stored in macrophage
3. Protoporphyrin ring opened --> biliverdin + CO2
4. Biliverdin --> bilirubin

Front 40

What level of haptoglobin is used as a marker of increased RBC destruction? (Increased/decreased)

Back 40

Decreased haptoglobin = increased RBC destruction

(Liver does not increase production of haptoglobin based on consumption)

*However, keep in mind that haptoglobin can also decrease due to liver disease

Front 41

When Hb tetramers dissociate into alpha-beta dimers during intravascular hemolysis, what do dimers complex to?

How are these complexes removed?

Back 41

Haptoglobin
(Removed from circulation by hepatocytes)

Front 42

What is the fate of excess Hb as a result of intravascular hemolysis?

Back 42

Excess Hb is filtered by glomerulus

1. May be phagocytosed by renal tubular cells
2. May appear in urine as free Hb or MetHb

Front 43

Hb spilled into urine and then phagocytized by renal tubule cells may be detected as ________ within tubular cells on an iron stain of urine.

What is this used as a marker for?

Back 43

Urine hemosiderin

Marker for intravascular hemolysis

Front 44

An RBC is normally a reticulocyte for how many days?

Back 44

4 days

3 days in marrow
1 day in blood

Front 45

What is the normal reticulocyte count?

Back 45

~0.5 - 2.5%

Front 46

Do fully mature RBCs contain RNA?

Back 46

No

(But reticulocytes do)

Front 47

How is the reticulocyte count calculated?

How is the corrected reticulocyte count calculated?

Back 47

Ratio of reticulocytes to total RBCs x 100

Pt retic count (%) x Pt hematocrit/ Normal hematocrit