3.19 STROM Overview of Hematopoiesis

Question 1

Epo

Answer 1

Endogenous/exogenous causes an increase in RBC, 90% produced by kidney (renal failure leads to anemia) and can give as drug to increase RBC

Question 2

TPO

Answer 2

Leads to increase in platelet formation

Question 3

G-CSF

Answer 3

Increase Neutrophils, decrease apoptosis, cause functional activation and decrease Monocytes

Question 4

GM-CSF

Answer 4

Multipotential growth factor with overlapping activity (upstream of G-CSF) still has action on increasing Neutrophils

Question 5

Maturation of Granulocyte

Answer 5

“BLAST” to
1st ID-able cell for path way: (1)promyelocyte
(2) Myelocyte
(3) Metamyelocyte
(4) Bands and (5) Neutrophils
-amplification at every step of all have more neutrophils than any other cell type-true with all of these pathways
-G-CSF is key regulator/stimulator of granulopoiesis/myelopoiesis

Question 6

Thrombopoiesis

Answer 6

“BLAST” to

(1) Immature Megakaryocytes
(2) Mature Megakaryocytes
- POLYPLOID: avg 16-32 haploid genomes at a time
- Make platelets
- PROPLATELETS get lopped off to form mature platelets

Question 7

Thrombopoietin Regulation of Thrombopoiesis

Answer 7

-Constantly made by liver
-bind both megakaryocytes (platelet production) and platelets (bind up and prevent mega binding)
-If platelet # is low TPO will be less bound an able to bind megakaryocytes leading to platelet production
(Endogenous Action)

Question 8

Maturation of granulocyte

Answer 8

“BLAST” to

(1) Pronormoblast
(2) Basophilic Erythroblast
(3) Polychromatophilic Erythroblast (accumulation of Hgb)
(4) Normochromic Erythroblast exit of nuclei turns into (5) Polychromasic reticulocyte and then matures to (6) RBC

Question 9

RBC induced Anemia b/c of Iron Deficiency

Answer 9

Morphology: (1) MICROCYTOSIS (small) and HYPOCHROMIA (Pale, lack Hgb)
(2) ANISOCYTOSIS (variable size) and POIKILOCYTOSIS (variable shape)

Question 10

Fe Absorption

Answer 10

GI Tract: Fe+++ (ferric) to Fe++ (ferrous) via Ascorbate
PLASMA: Fe++ to Fe+++ via serum oxidases
-loaded onto serum transferrin

Question 11

SERUM IRON TEST

Answer 11

-look at how much Fe is bound to transferrin in the plasma

Question 12

Total Iron Binding Capacity (TIBC)

Answer 12

Tells if Serum Iron is low due to reduced transferrin or not

• High binding capacity means there is plenty of transferrin waiting to bind Fe (means there is an Iron Deficiency)
• [Serum Fe]/TIBC =% of Transferrin Saturation
• Iron Def should also cause increase in serum transferrin production

Question 13

Soluble Transferrin Receptor Level

Answer 13

-Macrophages increase production in low iron state to try and get iron make so many they are measurable

Question 14

Measure Ferritin

Answer 14

Storage form of Iron

• Strom’s FAVORITE!!!
• Decreased ferritin in rarely caused by anything else other than Iron deficiency
• look for “trace” levels/barely detectable
• Macros taking up ferritin to make RBC but do not have enough IRON
• Will be depleted before anemia starts

Question 15

Thalassemia

Answer 15

-Globulin syn pathway
Heterogenous group of GENETIC disorders that result from decreased rate of synthesis of alpha or beta chain on Hgb
-Some can cause anemia

Question 16

Beta Chain Defects

Answer 16

Morphology: (1) microcytosis & hypochromia (like Fe Def but cells are smaller usually)
(2) Frequent target cells (nonspecific)
(3) can be severe if homo; mild or clinically insig if hetero (GOD’s WAY)
-Have two functional copies in normal
LAB VALUES:
(1) Microcytic anemia with (2) Normal or Increased RBC
-Use Hgb Electrophoresis Test to confirm
–look for increased Hgb A2: (alpha2,delta2) and will also see some fetal Hgb: (alpha2,delta2)
NORMAL: alpha2,beta2

Question 17

Alpha chain Defects

Answer 17

Normal has 4 functional alpha genes

-alpha thalassemia 1 trait: clinically irrelevant, only a single mutation on one gene (of 4)

Question 18

ALPHA THAL 2 TRAIT

Answer 18

mild microcytic anemia, see gamma4 chain (Bart’s)at birth and normall chains later in life
–2 defective alleles, diagnose with PCR under diagnosed

Question 19

Hgb H disease (beta4)

Answer 19

3 mutant alpha genes

• have excess beta chain they form tetramer that is a func Hgb
• commonly misdiagnosed as IRON DEF, variable degree of microcytic anemia
• Hgb electrophoresis to diagnose

Question 20

Hgb Bart’s (gamma4)

Answer 20

Four defective copies

• usaully lethal in utero
• if baby lives makes Bart’s Hgb, will no survive long enough to beta chain (takes time to develop)