Intro to RBC

Question 1

What is the difference between serum and plasma?

Answer 1

Serum is missing coagulation proteins b/c the blood was allowed to clot then centrifuged so clotting factors used up and centrifuged out

Question 2

What is the area of central palor?

Answer 2

The lighter part in the center of RBC. It is lighter b/c it contains less hemoglobin due to shape of RBC (biconcave disc). In normal RBC it is 1/3 area of RBC.

Question 3

What happens to the color of hematopoetic progenitor cells as they mature into RBC?

Answer 3

They start off looking fairly blue (basophilic) and become progressively pinker with maturity to RBC

Question 4

What is a reticulocyte?

Answer 4

A maturing hemotpoetic cell that is localized in the bone marrow and is becoming RBC. It has extruded its nucleus and is ready to leave bone marrow.

Question 5

What is erythropoietin?

Answer 5

Hormone made by kidney that senses levels of oxygen in blood. If oxygen is low, more of this hormone is made and it stimulates an increase in RBC production.

Question 6

What signaling pathway is utilized by Erythropoietin?

Answer 6

Jak/Stat

Question 7

What compound/pathway stimulates production of erythropoietin?

Answer 7

HIF-1alpha

Question 8

Describe the relationship between hematocrit levels and erythropoietin levels.

Answer 8

Question 9

Describe in general how a RBC is broken down.

Answer 9

It is engulfed by a macrophage. Its hemoglobin is degraded to enter the amino acid pool or to become heme. Heme is then used to make iron or bilirubin. Bilirubin is processed in the liver and secreted in the bile.

Question 10

What are the necessary nutrients for erythropoiesis?

Answer 10

VitB12

Folate

Iron

PLP (VitB6)

VitA

VitE

Zinc

Copper

Cobalt

Question 11

RBCs need to be very flexible and able to deform. What factors determine how well it is able to deform?

Answer 11

Cell shape (Surface Area : Volume ratio)

Cytoplasmic viscosity

Membrane deformability

Mechanical stability

Question 12

What happens if hemoglobin were damaged in an RBC?

Answer 12

It would cause Hb to precipitate and that would increase viscosity of cytoplasm –> decrease deformability of RBC

Question 13

How many days does RBC survive in circulation?

Answer 13

120 days

Question 14

Why is the pentose phosphate pathway so important in RBCs?

Answer 14

It is the only source of NADPH production, which is important for neutralizing ROS

Question 15

What compound is made during glycolysis in RBCs that is unique only to RBCs?

Answer 15

2,3 BPG –> decreases Hb affinity for O₂ allowing RBC to release O₂ to tissues

Question 16

Describe the structure of Hb.

Answer 16

There are 4 polypeptide chains, 2 alpha and 2 beta. Each contains a heme group in their center, which has an iron in its ferrous form, which is reduced. Each molecule of Hb can bind 4 O₂.

Question 17

Heme Synthesis

• What is the first step (reactant, product, enzyme)?
• What is the final step (reactant, product)?
• Where do each of these steps occur?
• Which steps are rate limiting?

Answer 17

• Glycine + succinyl coA –> delta aminolevulinic acid via enzyme ALA synthase
• Protopophrin IX –> Heme via insertion of Fe2+
• In mitochondria
• Both are rate limiting

Question 18

Fetal hemoglobin has what chains in their Hb?

Answer 18

2 alpha

2 gamma

Question 19

Label the graph:

• pO2 in the lungs
• pO2 where half Hb is bound to O2
• pO2 in tissues

Answer 19

Question 20

Describe the binding of O2 to Hb.

Answer 20

O2 binds in a cooperative manner. When the first O2 binds, it causes conformational change in shape of adjacent Hb chain making it easier for that chain to bind O2. This confers a change from the T state (tense) to the R state (Relaxed)

Question 21

• What does a right shift in the Hb-O₂ curve mean?
• What causes a right shift?

Answer 21

• It represents a decrease in the affinity of Hb for O₂
• Increasing temp, PCO₂, and [2,3 BPG] as well as decreasing pH

Question 22

When RBC is measured in the blood, what does that actually represent?

Answer 22

Absolute RBC count + Hemoglobin + Hematocrit

Question 23

What is spectrin?

Answer 23

It is a cytoplasmic protein that is responsible for anchoring integral membrane proteins in the RBC membrane to the interior of the cell. It is responsible for maintaining the RBC biconcave disc shape and the Surface Area : Volume ratio

Question 24

• What is a left shift in Hb dissociation curve?
• What causes this?

Answer 24

• Increasing affinity for O₂ binding
• Decrease temp, decrease PCO₂, 2,3 BPG, Increase pH

Question 25

Describe the Embden Meyerhof metabolic pathway in RBCs.

Answer 25

The only metabolic pathway in RBCs is glycolysis, which is referred to as this in RBCs because there are some unique differences from normal glycolysis. First, pyruvate is converted to lactate in the RBC at the end of glycolysis to regenerate NAD+. Additionally, the compound 2,3 BPG is made from 1,3 BPG in order to regulate Hb affinity for O₂ in the body.

Question 26

What are the key features / roles of glucose metabolism in an RBC?

Answer 26

• Anaerobic
• Supports membrane integrity b/c glucose 6P can be shunted to PPP to make NADHP
• Provides ATP for membrane ion pumps
• NADH produced by GAPDH (G3P –> 1,3 BPG) is used by methemglobin reductase to keep Fe in ferrous form (Fe2+)
• Formation 2,3 BPG to regulate Hb affinity for O2

Question 27

What subunits is fetal hemoglobin made up of?

Answer 27

2 x Alpha

2 x Gamma