Hematopoesis Flashcards Preview

Haematology > Hematopoesis > Flashcards

Flashcards in Hematopoesis Deck (96):
1

TPO does what

stimulates BFU(EMeg)--> CFU-MEG for platelet production

2

EPO does what

Stimulates BFU-E->CFU-E for RBC production

3

G-CSF does what

stimulates CFU-GM-->CFU-G for neutrophil production

4

GM-CSF does what?

acts on all blast cell lines

5

Cells involved in myeloposiesis (aka granulopoiesis)

Monocytes, Neutrophils, Eosinophils, basophils

6

Cells involved in ertyhropoiesis

red blood cells

7

cells involved in thrombopoiesis

platelets

8

cells involved in lymphopoiesis

T cells, B cells, NK cells

9

Which cells are defined as blasts (<4%)
*not identifyable microscopically but by their responsiveness to growth factors

PSC-->CFEGEMM and common myeloid progenitor

then BFUE-CFUGM-CFUbaso
(all of these are acted on by GMCSF)

10

List normal maturation of granulocyte

Blast-->
Promyelocyte-->
myelocyte-->
Metamyelocyte-->
bands-->
neutrophil

11

mature species outnumber younger species why?

because maturation is a process of DIFFERENTIATION alongside a process of DIVISION
(age=increase in rounds of division)

12

key regulator of granulopoiesis/ myelopoiesis

GM-CSF

13

eosinophils branch of when during myelopoiesis-->

between morphological bast stage and promyelocytes (in response to GM-CSF

14

G-CSF role in myelopoeisis

acts more specifically on neutrophil precursors

15

list the maturation of RBC's

blast-->
pronormoblast-->
basophillic erythroblast-->
polychromatophillic erythroblast-->
normochromic erythroblast

16

erythropiesis is under the control of which growth factor

Erythropoietin

17

EPO production is regulated by?

Hypoxia--> causes HIF-1 to be up-regulated which goes to nucleus and up-regulates EPO to be made and released by renal peritubular capillaries

18

renal failure can cause

ANEMIA: loss of EPO production and timely release

19

describe nascent RBC's

--> anucleate, polychromatic reticulocytes
(larger than usual, filled with RNA, so will stain with methylene blue)

20

Do blasts have nuclei

YES

21

Pletelet maturation

blast--> immature megakaryocyte--> mature megakaryocyte-->platelets

22

platelet production is under control of -->

TPO

23

describe megakaryocytes

poly ploid (16-32 haploid nuclei)--> extend snake-like protoplatelets into bone marrow blood vessels

24

TPO is made in the

liver

25

How does TPO work

binds megakaryocytes-->stimulates production from immature precursors and platelet production from immature megakaryocytes

26

low platelet count...

--> allows more TPO to bind megakaryocytes, stimulating more thrombopoiesis.

27

hematopoetic GFR's work via

JAK2 signal transduction
*acquired mutations here will give you cancer!

28

red cell production requirements

heme synthesis
globin synthesis
DNA synthesis
regulation

29

heme synthesis

iron
B6
succinyl Coa
glycine

30

hemoglobin=

heme + globin

31

heme=

iron + protoporphyrin

32

heme synthesis also requires...

B12 and folate

33

DNA synthesis requires

1. dNTP's-->thymidine (THYMINE)-->which requires B12 and folate
2. deoxynucleotide reductase

34

proper regulation of EPO requires

healthy kidneys
normal bone marrow micro-environment

35

Iron deficieny results in-->

red cells without enough hemoglobin

36

most common cause of microcytic hypochromatic anemia

iron Deficiency anemia

37

RDW correlates with

anisocytosis

38

Characteristic but not diagnostic of Iron def. anemia

poikilocytosis and anisocytosis

39

why is free plasma iron bad

causes free radicals
>would augment bacterial growth
(ergo iron is low during inflammatory state and hepcidin is up)

40

gastric environment that favors iron uptake

acidic (low pH)-->therefore co-admin of Vitamin C will increase the amount of iron one takes up

41

iron is absorbed in the...

deodenum

42

b12 is absorbed in the

illuem

43

iron travels in the blood

with ternsferrin--> in the ferrous state Fe3++

44

dietary iron-->

usually Fe+++

45

iron is transported into the enterocyte via

DMT1--> in the fe++ state

46

how does fe+++/transferrin get into the bone marrow to make heme

binds to transferrin receptor in erythroid precursors in the bone marrow

47

storage form of iron

ferritin

48

where is iron stored

macrophages in the liver, spleen bone marrow

49

how does iron get from gastric lumen into enterocyte

dmt-1

50

how is heme iron absorbed

heme carrier protein 1

51

how does iron get from enterocyte to plasma

ferroportin

52

inhibitor of feroportin

hepcidin

53

how is DMT1 regulated

iron dependent regulation of its mRNA

54

hepcidin transcription is increased by

IL-6 9we dont want the bacteria to have iron

55

TIBC goes up or down in infection

down-->bind up iron making it unavailable to bacteria

56

transporter responsible for moving iron from macrophages in storage pool-->making it available in plasma for erythroid precursors

ferroportin

57

Most useful measure of iron metabolism in anemias of unknown etiology

serum ferritin
(measures storage iron)

58

simplest measure of transferrin-bound iron

serum iron
*but does not directly address iron stores

59

Serum ferritin is propoertional to

amount of storage pool iron in the body

60

TIBC=

total amount of transferrin in ciruclation

61

transferrin saturation

serum iron (transferrin bound fe)// total transferrin
*tells us how active transport system is

62

UIBC=

TIBC-serum ferritin

63

WHen would you see an increase in Soluble Transferrin receptor?

when iron storage pool is depleted following loss of serum iron
*macrophages increase the amount of transferrin receptors--> manifests as increase in sTFR-->

64

reliable indicator between anemia or chronic disease and iron deficiency anemia

sTFR will be increased in iron deficiency anemia and NOT in anemia of chronic disease

65

ferritin is an

accute phase protein and will be elevated in inflamatory states

66

markers of Iron defieincy anemia

1. increased soluble transferrin receptor
2. decreased serum ferritin
3. decreased serum iron
4. increased TIBC
5. increased ferroportin

67

normal iron/transferrin levels increase or decrease hepdicin production

increase-->which decreases ferroportin and iron uptake

68

below average iron/transferrin levels increases or decreases hepcidin production

decreases --.ferroportin is increased and more iron is absorbed

69

reduced globin production=

thalassemia

70

characters of beta thalassema

microcytic, hypochromic, with target cells (nonspecific)

71

differentiates beta thal from IDA

MCV < 70 and a NORMAL or increased NUMBER OF BLOOD CELLS

72

IDA HAS NORMAL OR REDUCED # OF RBC'S

reduced

73

confirmation of beta thal-->

hg electrophoresis

74

normal heomoglobin : HgbA

alpha2beta2

75

HgA2

alpha2delta2

76

fetal Hgb

Alpha2gamma2

77

beta thalassemia will result in which types of Hgb in the adult

over production of Hgb delta--> so increased Hgb A2

78

beta thalassemias are more susceptible to...

point mutations

79

alpha thals are more susceptible to

deletions

80

Hgb H

three deletions of alpha globin gene--> result is beta tetramers-->increased afinity for O2-->poor deivery

81

Hgb Bart;s-->

deletion of four ALPHA alleles-->result is gamma tetramer, and fetus dies

82

which alpha thal can be confused for IDA

alpha thalassemia type 3

83

Type 2 alpha thal in adulthood

>normal hgb electrophoresis as adults
>mild microcytic anemia

84

Type 2 alpha thal prenatal

excess Hgb Barts at birth

85

Dx of Thalassemia 2 trait

Pcr based (electrophresis and/or sequencing)

86

overall cause of megaloblastic anemia

inhibition of DNA synthesis

87

causes leading to megaloblastic anemia

1. pernicious anemia-->b12 def.
2.impaired folate uptake
3. drug effect (HAART and hydroxyurea)
4. Myelodysplastic syndrome

88

Most megaloblastic anemias can be dx with...

bone marrow biopsy

89

the urge to breath is regulated by Co2

co2 concentration--> not o2

90

2 overall causes of reduced circulating red cell mass

1. decreased produciton of RBC's
2. increased loss of RBCs

91

discuss anemia of chronic inflammation

IL6 induces liver to produce--> increased hepcidin (acute phase reactant)--> decreased uptake and release from macorphages storage pool (via destrcution of ferroportin) --> erythroppiesis comes to a screeching HALT

92

normocytic anemias

1. anemia of chronic disease
2. thalassemias (sickle cell)
3. pregnancy
4.hemolysis
5.b2 or b6 defiency

93

Anemia of chronic disease will present as what?
(everybody is ordered off the street)

1. increased hepcidin-->ferroportin inhibited
2. therefore decreased serum iron
3. decreased transferrin
4. decreased TIBC
5. increased ferritin
*iron shunted from plasma-->into storage macrophages!***

94

confirmation of anemia of CD

bone marrow biopsy

95

chronic disease that can cause anemia

cancer of any type RA
TB
AIDS

96

reticulocyte count with ACD and IDA

will be low--> unable to compensate
also could be an EPO problem