erythrocytosis

Question 1

What does polycythemia look like on a blood smear?

Answer 1

Thicker RBCs

Increased RBCs

Question 2

What does the kidney do in response to anemia/hypoxia?

Answer 2

Decreased O₂ delivery causes the kidney to produce more Epo –> bone marrow produces new RBCs

Question 3

HIF1

Answer 3

Hypoxia inducing factor

• In hypoxic conditions, HIF1-a dimerizes with HIF1-B –> a transcription factor to increase transcription/translation of Epo
• Otherwise, HIF1-a is bound to VHL, undergoes ubiquitylation, and is degraded.

Question 4

What kind of signaling is Epo involved in?

Answer 4

cytokine

Epo binds its JAK/STAT receptor > dimerization > phosphorylation > promote stem cells in bone marrow to differentiate into rBCs

Question 5

What might cause erythrocytosis?

Answer 5

• Traveling to a higher altitude (hypoxic event causes stimulation of RBC production)
• Epo-secreting tumor
  
  • Pheochromocytoma
  • Hepatoma
  • Uterine leimyoma
  • Cerebella hemangioblastoma
  • Kidney cancers
• Constitutively active JAK/STAT

Question 6

Polycythemia vera

Answer 6

A type of myeloproliferative neoplasm where RBCs are proliferating due to a JAK2 mutation that leaves JAK2 constitutively active and promotes differentiation of stem cells to RBC

Question 7

If someone has polycythemia with HIGH epo vs LOW epo, what does it tell you?

Answer 7

Polycythemia w/ high epo –> the pathway is fxning fine, but there’ san external stressor (hypoxic event)

Polycythemia w/ low epo –> mutations within JAK/STAT caused the pathway to be constitutively active

Question 8

How does kidney cancer cause increased epo levels?

Answer 8

VHL is mutated

Question 9

HIF1-a increases production of ____, which causes vessel formation to deliver oxygen to tissues

Answer 9

VEGF (Vascular Endothelial Growth factor)