Erythropoiesis

Question 1

What are some causes of erythrocytosis/polycythemia?

Answer 1

Polycythemia Vera: monoclonal prolif of RBCs, low EPO
Chronic hypoxia
Increased EPO (secondary)
EPO-secreting tumors: Potentially Really High Hct
Pheochromocytoma
Renal Cell Carcinoma
Hepatocellular Carcinoma
Hemangioblastoma

60% of Down’s syndrome patients are born w/ polycythemia.

Question 2

What causes the basophilic stippling seen in lead poisoning?

Answer 2

aggregates of rRNA

Question 3

What are the features of lead poisoning?

Answer 3

LEAD
Lead lines gingivae, long bones
Encephalopathy
Abdominal colic and sideroblastic anemia
DRops-wrist and foot.

Question 4

What is the treatment for lead poisoning?

Answer 4

1st line: EDTA
succimer for kids
Dimercaperol for severe cases in kids

Question 5

What is:
HbA
HbA2
HbF
Hb Gower

Answer 5

HbA: 2alpha, 2gamma, 97% of adult hemoglobin
HbA2: 2%, 2alpha 2delta
HbF: fetal 2alpha 2 gamma (lower affinity for 2,3DPG
Hb Gower: Embryonic hemoglobin 2 zeta, 2 epsilon

Question 6

What is:
HbBart’s
HbH

Answer 6

HbBart’s: severe alpha thalassemia. 4 gammas, no alpha

HbH: severe alpha thalassemia: 4beta, no alpha

Question 7

What is:

HbS
HbC

Answer 7

HbS: Sickle cell hemoglobin, found in sickle cell patients
2alpha, 2betaS (glut–>val in beta chain)

HbC: hemoglobin C disease, seen in sickle cell patients
2alpha 2betaC (glut-->lys in beta chain)

Question 8

What’s the deal with fetal erythropoiesis?

Answer 8

Young Liver Synthesizes Blood
Yolk sac (3-8 wks)
Liver (6wks-->birth)
Spleen (10-28 weeks)
Bone Marrow (18 weeks-->adulthood)

Question 9

Which bones are involved in bone marrow stuff in childhood? Adulthood?

Answer 9

Childhood:
Sternum
Pelvis
Ribs
Cranial Bones
Vertebrae
Long Bones

Adulthood: axial
pelvis
vertebrae
ribs

Question 10

The first step of heme synthesis is the rate limiting step. What is the enzyme? What can inhibit this step? What is the disease associated with it?

Answer 10

ALA synthase
glucose and heme inhibit it
Sideroblastic Anemia (X linked)
Glycine + succinylCoa–>delta aminolevulinic acid

Question 11

What is the second step in heme synthesis? Which enzyme? Which disease?

Answer 11

dAL acid–>porphobilinogen
ALA dehydratase
inhibited by lead poisoning

Question 12

What is the 3rd step in heme synthesis? Enzyme? Disease?

Answer 12

porphobilinogen–>hydroxymethylbilane
Enzyme: porphobilinogen deaminase
Disease: acute intermittent porphyria

Question 13

Which step of heme synthesis does porphyria cutaena tarda mess up?

Answer 13

uroporphyrinogen III–>coproporphyrinogen III

Enzyme: uroporphyrinogen decarboxylase

Question 14

What is the last step of heme synthesis? Enzyme? Dx?

Answer 14

Protoporphyrin–>Heme
Enzyme: ferrochelatase
Dx: lead poisoning

Question 15

Once again, what is the affected enzyme and accumulated substrate w/ lead poisoning?

Answer 15

enzyme: ALA dehydratase, ferrochelatase

accumulated substrates: d-ALA, protoporphyrin

Question 16

What are the affected enzymes and accumulated substrates w/ acute intermittent porphyria?

Answer 16

affected enzymes: porphobilinogen deaminase

accumulated substrate: porphobilinogen, dALA, coporphobilinogen

Question 17

What are the symptoms of acute intermittent porphyria and treatment?

Answer 17

Treatment: glucose and heme, inhibit ALA synthase

Symptoms: 5Ps
Painful abdomen
port-wine colored urine
polyneuropathy
psych disturbances
precipitated by drugs that inhibit the Cyt P450

Question 18

Which disorder may present with intense itching after a hot shower?

Answer 18

polycythemia vera
release of basophils
also get erythromelalgia (severe burning pain and red-blue discoloration of extremities)

**JAK2 mutation