L4. RBC and Hb Flashcards
What is the normal structure of a mature RBC and its function
Discoid cell of 7um diameter with no nucleus, RNA or mitochondria
Function is carriage of Hb to allow gas exchange from lungs to tissues and vice versa - O2 transport.
What is special about the shape of RBC, what determines the shape and what is a clinical abnormality
The shape allows flexibility to go through 3.5um capillaries and increased area for gas exchange.
- Determined by membrane and cytoskeletal protein
so - Inherited abnormalities in membrane can result in shortened life span-haemolysis
(Hereditary spherocytosis)
How does RBC maintain osmotic equilibrium without mitochondria.
Why does it need to and what is a clinical problem related to this
RBC uses glycolytic pathways to produce ATP to maintain osmotic equilibrium.
- The HMP shunt produces NADPH which keeps Hb in reduced state which is important.
Clinical inherited defects in enzyme pathway lead to sensitivity to oxidative stress causing haemolysis (eg. kava beans, medications)
- eg. G6PD x linked deficiency
What is the most common type of Hb and what is it made of.
What are two clinical defects related to Hb production
HbA is most common;
made of 2 alpha globin and 2 B globin chains with 4 haem groups altogether
Inherited defect in a/b globin chains= thalassemia.
Deficiency in iron= reduced haem production
What are the main changes with differentiation from pronormoblast ->7-10days -> reticulocyte –>2–> mature RBC which circulate for 120 days
- Progressive increase in Hb - pinkness increases
- Chromatin clumping (condensing)
- Nucleus extruded out of the cytoplasm of the cell
- Loss of RNA
What is the earliest RBC released from the bone marrow,
how is it differentiated from mature RBC
and why do we count it- what does increase and decrease mean?
Reticulocyte has the nucleus extruded but it still contains RNA- mature RBC
These are measured (1-2%) and are measure of RBC production rate.
- Increase is related to blood loss, haemolysis
- Decrease related to bone marrow failure
What is the main regulator of RBC production, where is it produced and what causes increased production
Erythropoietin is glycoprotein produced in kidney by peritubular interstitial cells
Increased production due to reduced O2 delivery to the kidney
- anaemia
- renal stenosis
- blood loss
- high altitude
- COPD, HF
What are the main effects of regulator of RBC production and what is the negative feedback for its production
Binds to EPO receptor increase RBC production by
- Stimulation of CFU-E (and BFU-E at high amounts) (early stages of erythroid development)
- Increased Hb synthesis
- Reduced RBC maturation time
- Increased reticulocyte release
Therefore more Hb overall and increased O2 delivery which provides negative feedback
What are clinical conditions related to dysregulation of EPO
JAK2 mutation leading to constitutive activation and stimulation of EPO pathway without needing EPO.
Results in myeloproliferative neoplasms such as in
- Polycythemia vera - high haematocrit leading to thrombotic complications
- 50% of essential thrombocythemia ( too platelets) and primary myelofibrosis patients.
What are the clinical/other uses of recombinant EPO
Subsidised for use of anaemia caused by
- renal failure +
- preleukemic syndromes
- bone marrow cancers
Has potential for abuse by competitive cyclists to increase O2 supply
How are RBCs broken down after their 120 day life span - steps
- As it ages cells less deformable so removed in liver and spleen and sequestered there (+
reticuloendothelial system) - RBC is broken down to release Hb
- Hb broken down into
a) globin chains–> broken down into amino acids to be recycled
b) haem - Haem is broken down into
a) iron which is bound to transferrin and recycled in bone marrow
b) protoporphyrin which forms bilirubin in liver and excreted in bile (unconjugated bilirubin)
