Erythropoietin

where are these receptors expressed?

on red blood cell precursors in the bone marrow

What does an increase in RBCs lead to?

It is a negative feedback mechanism which suppresses erythropoietin synthesis

What treatment is available to those with renal anaemia

Iron supplementation and if that does not work, erythropoiesis stimulation

What interaction is possible between erythropoietin and angiotensin II?

Angiotensin II possibly increases Erythropoietin production as ACEi and ARBs reduce erythropoietin synthesis Erythropoietin treatment is associated with a decrease in plasma volume, there could be a link between this and inhibition of the RAAS system

What does erythropoietin do?

Controls red blood cell production, it is necessary for adequate supply of oxygen to organs and tissues

What gene is used to synthesise erythropoietin?

Epo gene

What are symptoms of anaemia?

Fatigue Poor exercise tolerance Reduced brain function Increased risk of heart disease

What initiates the increase in erythropoietin transcription

Hypoxia Low Iron Low haematocrit

What transcription factors are constantly expressed?

Hypoxia Inducible Transcription Factors (HIF-1α)

Why can an increase in haematocrit be dangerous?

Increased risk of blood clots

Why are kidneys the site of erythropoietin production?

Large blood supply with a stable oxygen supply

What are the consequences for failure to produce erythropoietin?

Reduced production of RBCs and oxygen to tissues Impaired quality of life (reduced exercise capacity and cognition) Transfusions may be required risking rejection Risk of left ventricular hypertrophy due to overwork of the heart Increase in Cardio Vascular Disease in patients with Chronic Kidney Disease (CKD) and anaemia compared to those with CKD without anaemia

Where is adult erythropoietin made?

Renal cortical peritubular fibroblasts

What happens to this TF with normal oxygen levels?

The 2 proline sections of HIF-1α are hydroxylated in the presence of O₂, Fe²⁺, and 2-oxoglutarate forming CO₂ in the process as well as succinate. The hydroxylation allows for the addition of the Von Hippel Lindau (VHL) protein which allows for the addition of 5 Ubiquitin molecules which are markers for destruction of the HIF-1α protein, preventing erythropoietin mRNA synthesis

What happens to this TF with low oxygen levels?

When in hypoxic conditions, hydroxylation of the proline sections on HIF-1α is inhibited, and HIF-1α is stabilised by forming a complex with HIF-1β. This then forms a complex with the Aryl Hydrocarbon Nuclear Translocator (AHNT) which activates gene transcription of erythropoietin mRNA

What type of receptor is activated by erythropoietin?

a Homo-dimeric JAK-STAT receptor

What does signalling by erythropoietin lead to?

a decrease in apoptosis of these precursors, increase in proliferation of the precursors, and an increase in differentiation of the precursors

What can a lack of red blood cells lead to?

anaemia

How can erythropoietin be abused?

as increases RBC count, can used to increase sport tolerance

Where is foetal erythropoietin made?

in the liver

what is haematocrit?

the ratio of red blood cells to blood volume