Erythropoiesis - Erythropoietin

Question 1

What is the most common condition that will increase the rate of RBC production?

Answer 1

Decrease in the quantity of oxygen transported to the tissues (hypoxia)

Question 2

State 4 situations in which will create the rate of RBC production.

Answer 2

1) hemorrhage
2) destruction of major portions of the bone marrow
3) high altitudes cause less oxygen concentration in the air
4) various diseases that reduce tissue blood flow

Question 3

How does the rate of RBC production increase as a result of haemorrhage?

Answer 3

As a result of haemorrhage, a person may become extremely anaemic.

Then the bone marrow begins to produce large quantities of RBCs.

Question 4

State a method by which major portions of the bone marrow may be destroyed.
How does rate of RBC production increase then?

Answer 4

Destroyed by X-ray therapy.

Causes hyperplasia of the remaining bone marrow to increase RBCs.

Question 5

How does air at high altitudes affect RBC production?

Answer 5

At high altitudes, the quantity and of O2 in air is very low.
Insufficient oxygen transported to tissues.
RBC production is greatly appreciated increased.

Question 6

Describe the various diseases that decrease tissue blood flow.

Answer 6

They particularly cause failure of oxygen absorption by the blood as it passes through the lungs. (therefore increases rate of RBC production)

Seen especially in,
- cardiac failure (prolonged)
- lung diseases
due to tissue hypoxia caused by these.

Therefore RBC production increases, with a resultant increase in hematocrit and usually, total blood volume.

Question 7

What kind of molecule is erythropoietin?

What is it’s molecular weight?

Answer 7

A glycoprotein

It’s molecular weight is about 34,000.

Question 8

What is the principal stimulus for RBC production in a low oxygen state of tissues?

Answer 8

Erythropoietin (circulating hormone)

(Not hypoxia; because hypoxia has little to no effect to stimulate RBC production. However, when the erythropoietin system is functional, hypoxia causes a marked increase in erythropoietin, which enhances the RBC production until the hypoxia is relieved)

Question 9

What percentage of erythropoietin in the body is formed by the kidney?

Where is the rest formed?

Answer 9

90%

In the liver

Question 10

According to studies,which parts of the kidney are mainly responsible for the secretion of erythropoietin hormone?

Answer 10

Fibroblast-like interstitial cells surrounding the tubules in the cortex and outer medulla
(where much of kidney’s oxygen consumption occurs)

Question 11

Renal tissue hypoxia leads to increased tissue levels of which compound?
What is the function of it?

Answer 11

Hypoxia-inducible factor-1 (HIF-1)

Serves as a transcription factor for a large number of hypoxia inducible genes
including the erythropoietin gene

Question 12

How does HIF-1 increase the erythropoietin synthesis?

Answer 12

It binds to a hypoxia response element in the erythropoietin gene, inducing transcription of messenger RNA, resulting in increased erythropoietin synthesis.

Question 13

Which phenomenon suggests that there might be a non renal sensor that sends an additional signal to the kidneys to produce erythropoietin?

Answer 13

When hypoxia in parts of the body other than kidneys, stimulates the erythropoietin secretion from kidneys.

Question 14

Name some secretions that stimulate erythropoietin production.

Answer 14

Norepinephrine
Epinephrine
several of the Prostaglandins

Question 15

10% of the normal erythropoietin in the body is formed in tissues other than the kidney. How much RBC formation does this induce?

Answer 15

One third to half of the RBC formation needed by the body.

Question 16

Which stage of erythropoiesis is stimulated by erythropoietin?

Answer 16

It stimulates the production of proerythroblasts from hematopoietic stem cells in the bone marrow.

(Also, once proerythroblasts are formed, erythropoietin causes these cells to pass more rapidly through the different erythroblastic stages than normal)

Question 17

What are the 2 important vitamins for the final maturation of the RBCs.

Answer 17

Vitamin B9 (Folic Acid)
Vitamin B12 (Cyanocobalamin)

Question 18

Why are Cyanocobalamin and Folic acid essential for the synthesis of DNA?

Answer 18

In different ways, they are required for the formation of thymidine triphosphate
(one of the essential building blocks of DNA)

Question 19

What does lack of vitamin B12 or folic acid cause?

Answer 19

Abnormal and diminished DNA
Failure of nuclear maturation and cell division

Maturation Failure (Failure of erythroblastic cells of the bone marrow to proliferate rapidly, producing ‘macrocytes’)

Question 20

What are macrocytes?

Answer 20

Larger than normal RBCs which have a flimsy membrane and are often irregular, large and oval instead of the usual biconcave disc shape.

Question 21

What is the functional defect of macrocytes?

Answer 21

They are poorly formed.
They are capable of carrying oxygen normally, but their fragility causes them to have a short life, half to one third of the normal.