Hematopoiesis

How do EyD produce energy?

• They have no nucleus, ribosomes, or mitochondria

• They rely on anaerobic glycolysis, Na/K ATPase, Ca pumps

What is the shape of EyD?

Flat biconcave discs 7micrometer diameter

Surface area/volume ratio

How do EyD produce energy?

• They have no nucleus, ribosomes, or mitochondria

• They rely on anaerobic glycolysis, Na/K ATPase, Ca pumps

What is the shape of EyD?

Flat biconcave discs 7micrometer diameter

Surface area/volume ratio

How does EyD remove CO2?

Increased CO2 removal by conversion to HCO3-

Blood is a transport medium for:??

• Water and electrolytes

• Delivery of O2, nutrients

• Removal of CO2, Urea

• Hormones

• Defense components, thrombocytes, clotting factors, leukocytes

• Carriers proteins

• Heat

How does Multi potential hematopoietic stem cell divide?

Asymmetric division, it either duplicates itself or creates common myeloid progenitor and common lymphoid progenitor(short term)

Extramedullary hematopoisis, pay attention to to this graph

What cytokine does MHSC need to become common myeloid progenitor?

SCF (stem cell factor)

What is cytokine is needed to go from common myeloid progenitor to erythrocyte?

Epo

What is thrombopoietin?

• Tpo (for megakaryocyte growth and development factor, MGDF)

• Gylcoprotein

• Produced mainly in the liver

What stimulates thrombocytes/platelet formation?

Tpo

What are some characteristics of thrombocytes?

• Derived from bone marrow

• Pinched off cytoplasmic sacs, anucleate

• 2-3 micrometer in diameter

What are the characteristics of primitive Erythrocytes(EryP)?

• Originate in yolk sac

• Nucleated

• Can divide in circulation

• Make embryonic hemoglobins HbE

What is the difference between EryD and EryP?

• EryD is made from gestation wk 5 in humans

• Originate in fetal liver

• It is smaller and makes fetal hemoglobin HbF

• It becomes enucleated prior to entering the blood

What does each Hgb subunit contain?

• heme

• central Fe2+

When is Hgb not able to bind to O?

When it is oxidized, it is the called Methemglobin

What is the lifespan of erythrocytes in humans? Rats?

120d in humans and 45d in rats

What protects Hgb membraned from oxidation?

Reduced glutathione (GSH)

What causes membrane stiffness in older erythrocyes?

Oxidation of sulfhydryl groups

Epo plays and obligatory role for…

A stem cell committing to become a proerythroblast

What are the transcription events that must occur in order to upregulate Epo production?

Hypoxia stabilizes hypoxia inducible factors(HIF1 alpha, HIF2 alpha) which translocate to the nucleus, bind HIFB, and initiate Epo gene transcription

EpoR is a ______ type receptor?

JAK STAT

How do effector inhibit the apoptosis of erythroid progenitors?

PI3K activated Bcl-xL and inhibits apoptosis

Without Epo, _____ and ______ inhibit erythropoiesis

CIS and HCO

Understand the phases of this pathway

Leukocytes mature in….. and migrate to …..

Blood, tissue

What are some important changes reticulocytes make as they mature?

• continue to assimilate iron

• after a few days, they lose RNA, ribosomes, mitochondria, and mature into erythrocytes

What is the cause of polycythemia vera?

• Erythrocytosis conidtions caused by a gain function mutation for JAK2, somatic mutation.

• Elevated HCT, decreased plasma volume

• Erythropoiesis even in the absence of Epo

What are the clinical presentation of polycythemia vera and how is it treated?

• thrombotic events(DVT, pulmonary embolism), hemorrhages, pruritis

• Therapeutics: Myelosuppression, phlebotomy, JAK2 inhibitors