RBC physiology

Question 1

Which lineage are red cells derived from?

Answer 1

Myeloid lineage

Question 2

What is the name given to RBC progenitors in the bone marrow?

Answer 2

Erythroblasts

Question 3

What are reticulocytes?

Answer 3

Immature red blood cells in the circulation. They remain in the marrow for about 1–2 days and are released into the circulation, where they lose their RNA and become mature red cells (erythrocytes) after another 1–2 days. Mature red cells are non-nucleated biconcave discs.

Question 4

What is erythropoeitin?

Answer 4

A hormone which controls erythropoiesis

Question 5

Where is erythropoeitin synthesised?

Answer 5

Produced in the peritubular cells in the kidneys (90%) and in the liver (10%)

Question 6

What determines EPO production?

Answer 6

Regulated mainly by tissue oxygen tension. Production is increased if there is hypoxia from whatever cause, e.g. anaemia or cardiac or pulmonary disease

Question 7

What does erythropoeitin do?

Answer 7

Stimulates an increase in the proportion of bone marrow precursor cells committed to erythropoiesis, and CFU-E are stimulated to proliferate and differentiate

Question 8

Describe the life cycle of the RBC

Answer 8

• Eryhtropoeisis is triggered by EPO.
• Erythropoesis takes place in the bone marrow, where haemopoietic stem cells differentiate and eventually shed their nuceli to become reticulocytes.
• Reticulocytes mature into normal RBCs after 24 hours.
• After about 100 days RBCs are removed from circulation through eryptosis.
• Following eryptosis the haemoglobin is broken down and recirculated.

Question 9

What is the structure of normal adult haemoglobin?

Answer 9

Adult Hb molecule (HbA) and two α and two β globin polypeptide chains (α2β2)

Question 10

What substances are required for red cell synthesis?

Answer 10

• Iron
• B12
• Folate
• Thiamine
• Vitamins

Question 11

Where is iron normally absorbed in the gut?

Answer 11

Duodenum

Question 12

Once absorbed into enterocytes, how is Iron transported out into the blood stream?

Answer 12

Ferroportin - a transmembrane protein which can be inhibited by hepcidin

Question 13

How is Iron transported in the blood?

Answer 13

Bound to plasma transferrin - β-globulin that is synthesized in the liver. Each transferrin molecule binds two atoms of ferric iron and is normally one-third saturated

Question 14

How is Iron stored in cells?

Answer 14

As Ferritin - intracellular protein that stores iron

Question 15

What regulates iron absorption?

Answer 15

• Recent dietary intake
• Iron body stores
• State of bone marrow erythropoiesis to the intestine

Question 16

What enzyme alters iron from its ferric to ferous form, so that it can be absorbed at the intestine?

Answer 16

Ferric Reductase

Question 17

What is the action of hepcidin?

Answer 17

Regulates the activity of the iron exporting protein ferroportin by binding to ferroportin causing its internalization and degradation, thereby decreasing iron efflux from iron exporting tissues into plasma

Question 18

What can cause high levels of hepcidin production, and thus lowering of iron absoprtion into plasma, and subseuqently lowering stores?

Answer 18

Inflammation

Question 19

What causes increased hepcidin production, and thus increase iron absorption into plasma?

Answer 19

• Anaemia
• Low iron stores
• Hypoxia

Question 20

Where is Vitamin B12 absorbed?

Answer 20

Terminal Ileum

Question 21

What is haemosiderin?

Answer 21

An insoluble iron–protein complex found in macrophages in the bone marrow, liver and spleen. It appears to be a complex of ferritin, denatured ferritin and other material.

The iron within deposits of hemosiderin is very poorly available to supply iron when needed

Question 22

Where are the main sites of iron storage?

Answer 22

• Reticuloendothelial cells
• Hepatocytes
• Skeletal muscle cells

Question 23

How is B12 absorbed?

Answer 23

In combination with Intrinsic factor, which is secreted by gastric parietal cells

Question 24

What is folic acid and what is its purpose?

Answer 24

Folic acid monoglutamate - glutamate which is involved in amino acid metabolism and DNA synthesis

Question 25

What is cooperative binding

Answer 25

The idea that the more oxygen bound to to a RBC increases the affinity of it binding more oxygen.

Question 26

What’s the Bohr effect

Answer 26

• Binding of carbon dioxide decreases the amouth of oxygen bound, decreasing the haemoglobin’s affinity for oxygen.

Question 27

What is the oxygen dissociation curve?

Answer 27

The oxygen dissociation curve describes the relationship between the percentage of saturated haemoglobin and partial pressure of oxygen in the blood. It is not affected by haemoglobin concentration

Question 28

What causes the oxygen dissociation curve to move to the left?

Answer 28

For given oxygen tension there is increased saturation of Hb with oxygen i.e. decreased oxygen delivery to tissues.

Shifts to L → Lower oxygen delivery, caused by

Low [H+] (alkali)

Low pCO2

Low 2,3-DPG

Low temperature

Question 29

What causes the oxygen dissociation curve to move to the right?

Answer 29

For given oxygen tension there is reduced saturation of Hb with oxygen i.e. enhanced oxygen delivery to tissues

‘CADET, face Right!’ for CO2, Acid, 2,3-DPG, Exercise and Temperature