RBC1TuesdayLectureGoodridge

Question 1

Primary function of RBCs

Answer 1

To transport O2 and CO2

Question 2

What are they made of (do they have nucleus or mitochondria)?

Answer 2

They are just membrane with hemoglobin (buck of hemoglobin). They do NOT have any nucleus or mitochondria. They do NOT have any orgenelles or DNA or anything other than hemoglobin and their cell membrane.

Question 3

Why Erythrocytes/RBCS? (Why not just hemoglobin in solution)

Answer 3

1) Separate cellular compartment - metabolism (within the cell) regulates transport of O2 and CO2
2) Control redox state of the compartment (reducing) separate from the serum (oxidizing)
3) Regulate binding of O2 to hemoglobin with specific intracellular effectors (e.g. 2,3BPG)

4) In solution, more dilute Hb TETRAMERS DISSOCIATE into inactive Hb dimers.
(If no RBCs to protect the tetramers, you would have to have INCREDIBLY THICK amount of Hemoglobin to keep them in the tetramer form, because the tetramer will naturally dissociate in solution to the alpha-beta dimers)

(Hemoglobin is made of 2alpha-beta dimers that are weakly/ionically attracted to each other to form tetramers, and these dissociate easily in solution. However, the alpha-beta dimer components have lots of small hydrophobic forces that end up being really strong so the alpha-beta dimers (the two subunit parts of Hb) will NOT disocciate in solution, only the Tetramer will dissociate So the RBC protects the hemoglobin to keep it in the Tetramer form)

(When Erythrocyte(RBC) hemolyzes/ruptures, all of the hemoglobin dissociates into blood, and so all of the hemoglobin tetramers dissociate into alpha-beta dimers)

Question 4

Myelodysplasia

Answer 4

Disease in which Red Blood Cell production in the bone marrow is not being made properly.

Treatment:Recombinant EPOs (e.g. Procrit, Epogen, Eprex) are used to treat decreased erythrocyte production

Question 5

Therapeutic Erythropoetin

Answer 5

Recombinant EPOs (e.g. Procrit, Epogen, Eprex) are used to treat decreased erythrocyte production
***Recombinant Erythropoetin (EPO) is more stable than regular EPO!  They changed some amino acids on this synthetic version so it would be more stable and degrade less rapidly.

• Decreased EPO synthesis in end-stage kidney disease (remember EPO is normally made in peritubullar capillaries of the kidneys)
• HIV patients treated with some reverse transcriptase inhibitors
• Cancer patients on some types of chemotherapy
• Blood loss following surgery
• Myelodysplasia (disease where bone marrow isn’t making RBC’s properly/decreased production of RBCs)

Question 6

A 40 year old man has end stage kidney failure and is very anemic. Which of the following proteins, injected IV, would stimulate production of RBCs in this patient?

A. HIF-1
B. Procrit
C. Erythropoetin 
D. All of the above
E. B and C only

Answer 6

Answer: E (B and C only)
This question mentioned “injected IV,” and this is why HIF-1 will not work. Normally HIF-1 is and intracellular protein induced during hypoxia to stimulate more transcription/production of EPO in the kidneys leading to more RBC production in Bone Marrow, but the HIF-1 must be “inside the cell” to work properly and increase transcription. If it is injected IV, it will just stay in the blood/not in the cells and have no effect.

Procrit is recombinant erythropoetin/synthetic/drug that increases RBC production in bone marrow. And EPO is normal version which would also increase production (but it has shorter half-life than recombinant version). Still both of these would work if injected IV.

Question 7

Properties of Erythrocytes

Answer 7

• Circulate 120 days on average; cleared by spleen
• Lack nuclei
• Lack synthesis of macromolecules; no cell division
• Lack mitochondria and other intracellular organelles
• Energy from glycolysis
• Reductive power from pentose phosphate pathway
• Pathways to prevent accumulation of oxidative damage

Question 8

Metabolic pathways in erythrocytes/RBCs

Answer 8

The precursor cell has a lot of same things present as any cell (DNA synthesis/replication, RNA synthesis, RNA, Heme synthesis, Lipid synthesis, Mitochondira (and ETC), Protein synthesis, TCA cycle, Glycolysis, and Pentose Phosphate Pathway)

**ADULT ERYTHROCYTES only have Glycolysis and Pentose Phosphate Pathway present! All others mentioned above are absent in Adult RBCs!

***If mitochondria and nucleus are present, it is NOT a RBC/erythrocyte!

Question 9

Erythrocyte Shape

Answer 9

*Biconcave
-Increases Surface Area for gas and solute exchange
-Increases deformability; permits passage through
“tight spots”

• Dependent on:
  
  • Structure of the cytoskeleton
  • Metabolic pathways
  • Structure of the membrane