Clinical Pathology - Hematopoiesis

Front 1

Heme synthesis occurs in most cells of the body except for mature RBCs. T or F

Back 1

True!!
- most occurs in the red cell precursors

Front 2

Vitamin B6 (pyridoxial phosphate) is required for which step in heme synthesis

Back 2

The firs step!
Condensation of succinyl-CoA + glycine to form delta-aminolevulinic acid (delta-ALA)

Front 3

Heme synthesis

Back 3

GLYCINE + SUCCINYL-CoA

(ALA synthase)

AMINOLEVULINIC ACID (ALA)

(porphobilinogen sythase)

PORPHOBILINOGEN
(TWO PATHWAYS FOLLOW)


1)
GLYCINE + SUCCINYL-CoA

(ALA synthase)

AMINOLEVULINIC ACID (ALA)

(porphobilinogen sythase)

PORPHOBILINOGEN

(uroporphyrinogen III synthase)

UROPORPHYRINOGEN III

(uroporphyrinogen III decarboxylase)

COPROPORPHYRINOGEN III

(coproporphyrinogen oxidase)

PROTOPORPHYRINOGEN III

(protoporphyrinogen III oxidase)

PROTOPORPHYRIN IX

(ferrochelatase)

HEME





2)GLYCINE + SUCCINYL-CoA

(ALA synthase)

AMINOLEVULINIC ACID (ALA)

(porphobilinogen sythase)

PORPHOBILINOGEN (PBG)

(PBG deaminase)

UROPORPHYRINOGEN I

(uroporphyrinogen I decarboxylase)

COPROPORPHYRINOGEN I

Front 4

Protoporphyrin is found in normal mature RBCs, however it can be increased in __

Back 4

lead poisoning and iron deficiency

- ferrochelatase normal incorportates iron (Fe(2+)) into protoporphyrin IX to form the final product HEME

Front 5

Reticulocytes can continue to produce hemoglobin for __ days after loss of its nucleus

Back 5

2 days

Front 6

normal adult HbA consists of __

Back 6

4 heme groups and 4 polypeptide chains (2 alpha and 2 beta)

Front 7

Important differences between old (senescent) and young RBCs

Back 7

Old RBCs have a smaller surface area, thus an increased mean cell hemoglobin concentration (MCHC), like spherocytes

As RBCs age, the loss sialic acid from their membranes, exposing an asialglycophorin antigen that elicits an autoantibody. Binding of this autoAb to senescent RBCs marks them for removal by the RES, mainly in the spleen

Front 8

Within macrophages, old RBC hemoglobin is broken down into __

Back 8

- iron, protoporphyrin, and globin
- iron is reutilized
- globin can be degraded back into amino acid pool
- protoprophyrin is not recycled!, it is metabolized and excreted

Front 9

Protoporphyrin is metabolized into __

Back 9

Within macropages:
Protoporphyrin split into 1 mol CO and 1 mol biliverdin
- CO is eventually exhaled

Biliverdin is reduced to bilirubin

In plasma:
bilirubin is transported, bound to albumin, to liver

In liver:
bilirubin is conjugated and excreted in bile

In intestine:
bacteria reduce bilirubin to form urobilinogens (including urobilinogen and stercbilinogen)

Front 10

Normal absolute reticulocyte count is __

Back 10

50 x 10^9/L or (1%)

- normal reticulocyte production is 50 x 10^9/L/day

Front 11

Corrected reticulocyte count and reticulocyte production index

Back 11

Correct the retic count for anemia and account for the different reticulocyte maturation times seen with various rates of production and early release from marrow

The correction factor is inversely proportional to the HCT:
HCT(retic maturation time in days)

45(1.0)
35(1.5)
25(2.0)
15(2.5)

Determine the corrected reticulocyte count
Correct retic count = Pt HCT/nml HCT x Pt retic%/nml retic%

Determine the RPI (reticulocyte production index) to assess marrow response to anemia

RPI= corrected retic count/maturation factor

RPI divides anemias into proliferative anemias (hemolysis, hemorrhage, response to hematinic agents) and hypoproliferative anemias (marrow failure, iron deficiency, renal failure, endocrinopathies)

RPI>3 proliferative anemia
RPI<3 hypoproliferative anemia