Erythropoiesis

Question 1

What engulfs old RBCs?

Answer 1

Phagocytic cells of the liver and spleen

Question 2

What are globular haemoglobin proteins broken down into after RBC break down?

Answer 2

Amino acids which enter the blood stream
Haem group (minus iron) is converted to bilirubin
Bilirubin is transported to liver and secreted into bile

Question 3

What happens to iron after RBC breakdown?

Answer 3

Finds to transferrin in the blood and is recycled

Question 4

What is erythrocyte production regulated by?

Answer 4

Erythropoietin (EPO)

Question 5

Where is EPO released from?

Answer 5

Kidney

Question 6

What is the process from myeloid stem cell to mature erythrocyte?

Answer 6

Proerythroblast (derived from myeloid stem cells)
Polychromatic erythroblast (Hb in cytoplasm)
Orthochromatic erythroblast (Nucleus shrinks, full complement of Hb in cytoplasm)
Erythroblast excludes nucleus
Reticulocyte into circulation
Mature erythrocyte

Question 7

What is the shape of RBCs described as?

Answer 7

Biconcave disc

Question 8

What are the approximate sizes of RBCs?

Answer 8

8 (micro)m diameter
2 (micro)m thick at edge
1 (micro)m thick in centre

Question 9

What % of blood is plasma?

Answer 9

55%

Question 10

What % of blood is the buffy coat and what is its constituents?

Answer 10

1%

Platelets and WBCs

Question 11

What is haematocrit?

Answer 11

% RBCs

Question 12

What makes up packed cell volume?

Answer 12

Everything but plasma

Question 13

What regulates RBC ion balance volume?

Answer 13

Sodium pump

Question 14

How is ATP synthesised in RBCs?

Answer 14

Anaerobic glycolysis

Question 15

What helps keep iron in Fe2+ state?

Answer 15

NADH from glycolysis

Question 16

What is partly metabolised through a hexose monophosphate shunt, and what does this shunt do?

Answer 16

Glucose

Produces NADPH, required for maintenance of adequate levels of reduced glutathione

Question 17

What is produced when PO2 is reduced?

Answer 17

2,3 biphosphoglycerate- releases O2 from Hb

Question 18

What is glutathione?

Answer 18

Tripeptide, consisting of glutamate, cysteine and glycine

Question 19

What does glutathione do?

Answer 19

Reduced glutathione (it’s normal state) combats oxidative stress

Question 20

What are ROS?

Answer 20

Free radicals- highly reactive molecules with unpaired electrons

Question 21

What does excessive free radicals or inadequate antioxidant defence mechanisms lead to?

Answer 21

Damage of cellular structures and enzymes

Question 22

What does glutathione protect against?

Answer 22

Toxic effects of ROS

Also essential to detoxify hydrogen peroxide, the primary intermediate in oxidative damage

Question 23

What can glucose 6-phosphate dehydrogenase insufficiency cause?

Answer 23

NADPH deficiency, leading to reduced glutathione, leading to cell damage

Question 24

What 3 forms is CO2 produced by tissues carried to the lungs in?

Answer 24

Physically dissolved in solution (10%)
Bound to Hb-carbamino-haemoglobin (30%)
As bicarbonate ion (60%)

Question 25

What is CO2 transport facilitated by?

Answer 25

Carbonic anhydrase

Question 26

What happens in the Cl- shift?

Answer 26

Chloride/bicarb exchange- exports HCO3- (facilitated diffusion) Cl- enters to preserve cell potential

Question 27

What is the structure of Adult Hb?

Answer 27

4 globin sub units, each containing a single haem molecule Haem group contains single Fe2+ ion Each haem group can bind one O2 molecule

Question 28

When fully saturated, how much O2 will 1g Hb bind?

Answer 28

1.34ml

Question 29

What is required for Hb synthesis?

Answer 29

Synthesis of globin chains- 4 per molecule of Hb Synthesis of porphyrin ring (haem group) Insertion of iron into haem

Question 30

What globin sub units make up adult and foetal Hb?

Answer 30

HbF- predominantly a2y2, in late gestation y expression falls, B expression rises HbA- predominantly a2B2

Question 31

Do allosteric interactions (e.g. O2 binding to Hb) follow Michaelis-Menten kinetics?

Answer 31

No

Question 32

What does increasing substrate concentration in allosteric interactions result in?

Answer 32

Sigmoidal curve rather than hyperbola, indicating co-operative behavior

Question 33

What is co-operativity in allosteric interactions?

Answer 33

The influence that the binding of a ligand to one site on the molecule has on the binding of ligand to a different functional site

Question 34

Describe the Hb dissociation curve in terms of arterial and venous blood

Answer 34

Arterial- plateau phase sustains SaO2 >90% over wide range of inspired (blood) pO2 Venous- steep phase of curve favours O2 offloading to tissues

Question 35

Does HbF have a higher affinity for O2 and 2,3 BPG than HbA?

Answer 35

Higher for O2, lower for 2,3 BPG | This facilitates the transfer of O2 from mother to foetus