Hem 4 - Erythropoiesis

Question 1

When and where do the primitive blood cell progenitors appear? And where do the true hematopoietic stem cells come from And later migrate to?

Answer 1

The appear in the yolk sac at about 3 weeks. The true hematopoietic stem cells come from near the mesonephros and migrate to the liver.

Question 2

Where is blood synthesized in the fetus?

Answer 2

[Young Liver Synthesizes Blood] hematopoiesis starts off in the Yolk sac from week 3 until about week 8. Liver and the Spleen; liver is the most important site of hematopoiesis thru fetal development. around week 28, the primary site of hematopoiesis is the Bone marrow.

Question 3

What are the globin chains in the RBC of an Adult?

Answer 3

2 alpha-chains and 2 beta-chains.

Question 4

What are the globin chains in the RBC of a fetus?

Answer 4

2 alpha-chains and 2 gamma chains.

Question 5

What is special about gamma chains found in fetus RBC?

Answer 5

They have lower affinity for 2,3-DPG and a higher affinity for O2.

Question 6

Where do we see and what is the structure of Hb A?

Answer 6

Found in 97% of normal hemoglobin. Structure is 2 alpha chains and 2 beta chains.

Question 7

Where do we see and what is the structure of Hb A2?

Answer 7

Found in 2% of normal hemoglobin. Structure is 2 alpha and 2 delta.

Question 8

Where do we see and what is the structure of Hb A1c?

Answer 8

Seen in poorly-controlled diabetes. Structure is 2 alpha and 2beta-glucose.

Question 9

Where do we see and what is the structure of Hb F?

Answer 9

Found in fetal hemoglobin. Structure is 2 alpha, 2 gamma chians.

Question 10

Where do we see and what is the structure of Hb Gower?

Answer 10

Found in embryonic hemoglobin. Structure is 2 zeta chains and 2 epsilon chains.

Question 11

Where do we see and what is the structure of Hb S?

Answer 11

Found in Sickle cell hemoglobin. Structure is 2 alpha, 2 beta (single amino acid substitution from glutamine to valine In beta chain).

Question 12

Where do we see and what is the structure of Hb C?

Answer 12

Found in Hemoglobin C disease. Structure is 2 alpha, 2 beta (glutamine has been changed for lysine in beta chain).

Question 13

Where do we see and what is the structure of Hb Bart’s?

Answer 13

Seen in severe alpha-thalassemia. Structure is 4 gamma chains (no alpha chains).

Question 14

Where do we see and what is the structure of Hb H?

Answer 14

Found in severe alpha-thalassemia. Structure is 4 beta chains. No alpha chains.

Question 15

What is the rate limiting enzyme of heme synthesis?

Answer 15

Aminolevulinic acid synthase. Glycine and succinyl-CoA are the substrates. Vitamin B6 is a necessary co-factor.

Question 16

What is the cause of acute intermittent porphyria And the symptoms?

Answer 16

Caused by deficiency of uroporphyrinogen-1-synthase. AKA porphobilinogen deaminase. Causes abdominal pain, port wine urine, and polyneuropathy and psychological disturbances. It can be precipitated by drugs (barbiturates, seizure drugs, rifampin, and metoclopramide).

Question 17

What is the treatment for acute intermittent porphyria?

Answer 17

Treat by giving glucose and heme, which inhibit the ALA synthase.

Question 18

What is the cause of Porphyria cutanea tarda and what are the symptoms?

Answer 18

Caused by Uroporphyrinogen decarboxylase. Causes blistering of the skin and photosensitivity, tea-colored urine, hypertrichosis, facial hyperpigmentation

Question 19

Which type of porphyria is the most common?

Answer 19

Porphyria cutanea tarda.

Question 20

Which three factors are associated w/ porphyria cutanea tarda?

Answer 20

Hepatitis C. Alcoholism. Elevation of LFTs.

Question 21

What two things does lead poisoning affect in the heme synthesis pathway?

Answer 21

ALA dehydratase. Ferrochelatase.

Question 22

What would inhibition of ferrochelatase cause in the RBCs?

Answer 22

RBCs will have increased levels of protoporphyrin.

Question 23

What does lead poisoning cause?

Answer 23

Microcytic anemia (And basophilic stippling, and ringed sideroblastic anemia) and neurological manifestations; global encephalopathy w/ memory loss and delirium and mental deterioration, foot drop or wrist drop. Lead lines on the gingivae (Burton’s line) and metaphysis. Colicky abdominal pain and renal failure.

Question 24

What is the treatment for lead poisoning?

Answer 24

EDTA or succimer in either kids or adults. Kids w/ severe toxicity and very high levels, give dimercaprol + succimer.7

Question 25

What is Polycythemia vera?

Answer 25

Monoclonal proliferation of red cells; benign red cell neoplasm.

Question 26

What are the 4 tumors that secrete EPO (erythropoietin)?

Answer 26

[Potentially Really High Hematrocrit] Pheochromocytoma, Renal cell carcinoma, Hepatocellular carcinoma, Hemangioblastoma.

Question 27

What is the difference b/w Relative polycythemia and Absolute polycythemia?

Answer 27

Relative: Plasma volume is reduced, therefore red cell count is increased relative to the plasma volume. Absolute: Plasma volume is normal; they just have too many red cells.

Question 28

What are 4 different causes of polycythemia?

Answer 28

Elevated EPO (pheochromocytoma, RCC, HCC, Hemangioblastoma). Chronic hypoxia. Polycythemia vera. Trisomy 21.

Question 29

What are the non-hematologic findings of lead poisoning?

Answer 29

Encephalopathy. Memory loss. Headaches. Foot and wrist drop. Lead line on gingivae. Lead lines on the bones (children). Abdominal colic. Renal failure.

Question 30

What are the hematologic findings of lead poisoning?

Answer 30

Microcytic anemia. Basophilic stippling. Ringed sideroblasts in bone marrow.