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Hematology 1 > Module 1: Normal Blood Components, Production, and Erythrocytes > Flashcards

Module 1: Normal Blood Components, Production, and Erythrocytes Flashcards

1
Q

Define hematopoieses

A

Production and development of blood cells

Constant restoring of various blood cells

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2
Q

What does the hematopoietic system consist of?

A

Bone marrow, liver, spleen, thymus, and lymph nodes

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3
Q

What cells does erythropoieses produce? Leukopoiesis? Thrombopoiesis?

A

Red blood cells, white blood cells, and plateltes

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4
Q

What are myeloid cells?

A

Blood cells produced in the bone marrow

All blood cells except for lymphocytes

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5
Q

What are non-myeloid cells?

A

Blood cells not produced in the bone marrow

Lymphocytes, produced in the lymph nodes

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6
Q

What is medullaary hematopoiesis?

A

Production of myeloid cells in the bone marrow

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7
Q

What is extra-medullary hematopoiesis?

A

Production of myeloid cells outside of the bone marrow

**Not normal is adults!

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8
Q

What are the 3 stages of hematopoiesis?

A

Mesoblastic, hepatic, and myeloid

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9
Q

What is the mesoblastic phase of hematopoiesis?

A

2nd - 12th gestational weeks

Yolk sac and embryo form primitive blood stem cells (erythroblasts)

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10
Q

What is the hepatic phase of hematopoiesis?

A

6th gestational week to 2 weeks old
Liver and spleen produce more mature erythrocytes, then granulocytes, the monocytes
Lymph nodes begin forming lymphocytes
Bone marrow forms at 8 weeks gestation

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11
Q

What is the myeloid phase of hematopoiesis?

A

20th week gestation to death
Lymph nodes produce lymphocytes, bone marrow produces myeloid cells
Liver and spleen have potential for hematopoiesis if needed

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12
Q

What is the hematopoietic inductive microenvironment?

A

The bone marrow where myeloid cells can be produced and differentiate

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13
Q

What is the difference between red and yellow bone marrow?

A

Red - active bone marrow that can undergo hematopoiesis (children)
Yellow - inactive bone marrow, mostly fat (adults)

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14
Q

How is the liver involved with hematopoiesis?

A

Produces myeloid cells during gestation
In adults, synthesizes and produces transport proteins, stores vitamins and minerals for DNA and RNA synthesis, and breaks down hemoglobin

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15
Q

How is the spleen involved in hematopoiesis?

A

Produces myeloid cells during gestation

In adults, removes old and damaged RBC’s, and stores platelets

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16
Q

How does a splenectomy affect hematopoiesis?

A

Can no longer remove defective RBC’s
Increased platelets, increased poikilocytosis, increased denatured hemoglobin in RBC’s (Heinz bodies), increased retained nuclear material in RBC’s (Howell-Jolly bodies)

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17
Q

How is the thymus involved in hematopoiesis?

A

Production and maturation of T-lymphocytes

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18
Q

How are the lymph nodes involved in hematopoiesis?

A

Form new lymphocytes

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19
Q

What are stem cells?

A

Primitive, formative, unspecialized blood cells with potential to become several types of specialized blood cells

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20
Q

What is the most primitive hematopoietic stem cell?

A

Reticulum Cell

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21
Q

What can the reticulum stem cell differentiate into?

A

CFU-S (Colony forming unit - stem)

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22
Q

What is a CFU-S cell?

A

Colony forming unit - stem
pluripotential blood stem cell
multipotent lymphohematopoietic stem cell

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23
Q

What might a CFU-S stem cell differentiate into?

A

CFU-GEMM or CFU-L

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24
Q

What is a CFU-L stem cell?

A

Colony forming unti - Lymphoid

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25
Q

What may a CFU-L stem cell differentiate into?

A

Lymphocyte precursor cells
B-cell precursor
T-cell precursor
NK cell precursor

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26
Q

What is a CFU-GEMM stem cell?

A

Colony forming unit - Granulocyte, erythroid, monocyte, megakaryocyte
Myeloid stem cell

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27
Q

What might a CFU-GEMM stem cell differentiate into?

A 
CFU-Eo (eosnophils)
CFU-Baso (basophils)
CFU-GM (granulocyte, monocyte)
BFU-E (Burst forming unit - erythroid)
BFU-Meg (Burst forming unit - megakaryocyte)
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28
Q

What is a CFU-GM stem cell?

A

Colony forming unit - granulocyte, monocyte

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29
Q

What might a CFU-GM stem cell differentiate into?

A

CFU-G

CFU-M

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30
Q

What is a blast cell?

A

Earliest stage of a blood cell that can be identified as the precursor to a certain cell line

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31
Q

What are growth factors?

A

Proteins that ind to cells resulting in their activation and cellular proliferation/maturation

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32
Q

What are the 3 most important growth factors in hematopoiesis? What is each secreted from?

A

Colony stimulating factor (CSF) and interleukins (IL) - macrophages, lymphocytes, and bone marrow stromal cells (fibroblasts, endothelial cells)
Erythropoietin (EPO) - kidneys
Thrombopoietin (TPO) - liver

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33
Q

What are cytokines?

A

Multi-functional, potent, low molecular weight glycoprotein chemical mediators, secreted locally and inhibit or induce cellular RNA or protein synthesis.

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34
Q

What are cytokines secreted by?

A

T-lymphocytes (lymphokines) and monocytes/macrophages (monokines)

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35
Q

What 3 growth factors do monocytes/macrophages produce?

A

Tissue necrosis factor
Interleukin-1
Interleukin-6

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36
Q

What 2 monocyte/macrophage produced growth factors work together? How?

A

Tissue necrosis factor + Interleukin-1

Activate and stimulate T-cells and bone marrow stromal cells to produce cytokines

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37
Q

What does Interleukin-6 do?

A

Stimulates B-cells to differentiate and produce antibodies, induces acute phase response to protein production by liver cells
Augments responses of immune cells to hematopoietic growth factors and cytokines

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38
Q

What growth factors do T-lymphocytes produce?

A

Stem cell factor
Flt ligand
Interleukin-3
Interleukin-5

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39
Q

What 3 T-lymphocyte produced growth factors work together? How?

A

Stem cell factor + Flt ligand +Interleukin-3

Induce CFU-S cell to differentiate into CFU-GEMM or CFU-L and undergo mitosis

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40
Q

What does Interleukin-5 do?

A

Induces eosinophil growth and function

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41
Q

What growth factors do bone marrow stromal cells produce?

A

Granulocyte/monocyte stimulating factor
Granulocyte (neutrophil) stimulating factor
Monocyte/macrophage stimulating factor

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42
Q

What does granulocyte/monocyte stimulating factor do?

A

Induces CFU-GEMM cells to differentiate into CFU-Eo, CFU-baso, CFU-GM, BFU-E, and BFU-meg cells and undergo mitosis

Stimulates phagocytic and cytotoxic functions in neutrophils and macrophages

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43
Q

What does granulocyte (neutrophil) stimulating factor do?

A

Induces maturation and mitosis of CFU-G and myeloblast cells

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44
Q

What does monocyte/macrophage stimulating factor do?

A

Induces maturation and mitosis of CFU-M and monoblast cells

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45
Q

What growth factors do kidney cells (juxtaglomerular region) produce?

A

Erythropoietin

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46
Q

What does erythropoietin do?

A

Induces maturation and mitosis of BFU-E, CFU-E, pronormoblasts, and NRBC’s

May induce other myeloid cell production if increased for a long period of time

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47
Q

What growth factors do liver cells as well as macrophages and endothelial cells produce?

A

Thrombopoietin

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48
Q

What does thrombopoietin do?

A

Induces maturation and mitosis of CFU-meg and megakaryocyte cells

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49
Q

What is tissue necrosis factor produced by?

A

Monocytes and macrophages

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50
Q

What is Interleukin-1 produced by?

A

Monocytes and macrophages

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51
Q

What is Interleukin-6 produced by?

A

Monocytes and macrophages

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52
Q

What is stem cell factor produced by?

A

T-lymphocytes

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53
Q

What is flt ligand produced by?

A

T-lymphocytes

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54
Q

What is Interleukin-3 produced by?

A

T-lymphocytes

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55
Q

What is Interleukin-5 produced by?

A

T-lymphocytes

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56
Q

What is granulocyte/monocyte stimulating factor produced by?

A

Bone marrow stromal cells

ex: fibroblasts, endothelial cells

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57
Q

What is granulocyte (neutrophil) stimulating factor produced by?

A

Bone marrow stromal cells

ex: fibroblasts, endothelial cells

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58
Q

What is monocyte/macrophage stimulating factor produced by?

A

Bone marrow stromal cells

ex: fibroblasts, endothelial cells

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59
Q

What is erythropoietin produced by?

A

Kidney cells (juxtaglomerular region)

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60
Q

What is thrombopoietin produced by?

A

Liver cells, macrophages, and endothelial cells

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61
Q

Define effective erythropoiesis

A

85% or more of developing RBCs in marrow are produced and released into the blood

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62
Q

Define ineffective erythropoiesis

A

Less than 85% of the developing RBC’s in marrow are produced normally and make it into the blood
(more than 15% die)

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63
Q

How long do NRBCs survive in the bone marrow and blood?

A

5 days and 0 days

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64
Q

How long do reticulocytes survive in the bone marrow and blood?

A

3 days and 1 day

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65
Q

How long do erythrocytes survive in the bone marrow and blood?

A

1 day and 110-120 days

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66
Q

How long do magakaryocytes survive in the bone marrow and blood?

A

7 days and 0 days

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67
Q

How long do platelets survive in the bone marrow and blood?

A

0 days and 8-10 days

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68
Q

How long do immature neutrophils survive in the bone marrow and blood?

A

5 days and 0 days

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69
Q

How long do bands and segmented neutrophils survive in the bone marrow, blood, and tissues?

A

7 days, 8 hours, and up to 6 days

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70
Q

How is increased demand for blood cells handled in the body?

A
  1. Bone marrow releases immature forms (left shift)
  2. Cell undergo more divisions
  3. Accelerating maturation time
  4. Increasing hematopoiesis in inactive areas
    • increasing # of blast cells
    • activating stem cells -> blasts (yellow marrow to red)
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71
Q

What are the 4 morphological changes that occur during blood cell maturation?

A
  1. Cell size decrease
  2. Nuclear/cytoplasmic ratio decrease
  3. Nuclear maturation (smaller, lose nucleoli, more clumping)
  4. Cytoplasm maturation (smaller, less blue, more pink)
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72
Q

How does each morphological feature change with maturation?

Cell size
Nuclear/cytoplasmic ratio
Chromatin pattern
Presence of nucleoli
Cytoplasm color
Cytoplasm granulation
Cytoplasm vacuoles
A 
Decreases
Decreases
More condensed
Not in mature cells
Dark blue, light blue, blue-gray/pink
No granules to non-specific to specific
Increase with age
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73
Q

What is it called when a cells nucleus and cytoplasm develop at different rates?

A

Nuclear cytoplasmic asynchrony
OR
dyspoiesis

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74
Q

Define nuclear cytoplasmic asynchrony / dyspoiesis

A

Nuclear differentiation lags behind cytoplasm, or vise versa

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75
Q

Name the 6 stages of erythrocyte development

A
  1. Pronormoblast (Rubriblast)
  2. Basophilic normoblast (Prorubricyte)
  3. Polychromatic normoblast (Rubricyte)
  4. Orthochromic normoblast (Metarubricyte)
  5. Polychromatiophilic (Reticulocyte)
  6. Erythrocyte
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76
Q

Describe the morphology of a pronormoblast

A

14-24μ
round central red-ish unclumped nucleus
0-2 nucleoli
small deep blue cytoplasm

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77
Q

Describe the morphology of a basophilic normoblast

A

12-17μ
Round/oval central/eccentric slightly clumped nucleus with parachromatin but no nucleoli
small deep blue/purple cytoplasm

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78
Q

Describe the morphology of a polychromatic normoblast

A

10-15μ
Round/oval central/eccentric deep purple/black heavily clumped nucleus with parachromatin and no nucleoli
Small 4:1-2:1 polychromatic cytoplasm

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79
Q

Describe the morphology of a orthochromic normoblast

A

8-12μ
Round central pyknotic black/brown nucleus
Moderate bluish-pink cytoplasm

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80
Q

Describe the morphology of a reticulocyte

A

7-10μ
No nucleus
Clear gray/blue cytoplasm, polychromatic to pink

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81
Q

Describe the morphology of an erythrocyte

A

7-8μ
No nucleus
Pink cytoplasm

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82
Q

Describe the plasma membrane of a red blood cell

A

Double bipolar lipid layer
50% protein 40% lipid 10% carbohydrate
Contains structural and contractile proteins (actin and spectrin), ATPase enzymes, surface antigens (A, B, H, etc), and receptor protein molecules (TfR)

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83
Q

Describe the structure of an RBC plasma membrane in regards to the lipid present

A

Two layers of glyco and phospholipids, polar group on the outside (bipolar)
Glycolipids are antigens on the outer surface
Cholesterol strengthens it

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84
Q

Describe the structure of an RBC plasma membrane in regards to the protein

A

Structural proteins are integral (penetrate membrane, glycophorin A) or peripheral (outside, spectrin)
If lipids attached, may be antigenic
Spectrin and actin maintain biconcave disk
Band 3 channels ions

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85
Q

Describe the structure of the RBC plasma membrane in regards to the carbohydrates

A

Thin mucopolysaccharide layer on surface

Oligosaccharides attached to lipids and proteins as antigens

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86
Q

Define selective permeability

A

Ability to selectively allow molecules to move in and out of the membrane according to cell requirement

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87
Q

What are the 3 functions of the RBC plasma membrane?

A
  1. Diffusion - water and lipid-soluble molecules cross
  2. Facilitated diffusion - molecules cross by attaching to transport molecules (ex: glucose mediated by insulin)
  3. Active transport - movement against concentration or electrical gradients, requires ATP and transport enzymes
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88
Q

Describe the sodium potassium pump

A

1 molecule of ATP pumps 2 molecules of K into the cell and 3 molecules of Na out of the cell against concentration gradients

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89
Q

Describe the calcium pump

A

ATP pumps Ca out of the cell

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90
Q

What happens when calcium builds up inside an RBC?

A

Elasticity is lost and hemolysis will occur

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91
Q

Why do RBC membranes have a negative charge?

A

To repel other RBCs in the blood to prevent damage by collisions

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92
Q

What happens when Na builds up inside an RBC?

A

Water follows Na into the cell causing swelling and hemolysis

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93
Q

What is present in an erythrocyte?

A

About 250 million hemoglobin molecules, organelles, enzymes, electrolytes, carbohydrates, lipids, and proteins

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94
Q

When is hemoglobin produced?

A

During RBC maturation
65% in normoblasts
35% in reticulocytes

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95
Q

What is required for hemoglobin production?

A

Iron, and other nutrients

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96
Q

What is hemoglobin made of?

A

Globin (4 polypeptide chains) and 4 heme molecules (protoporphyrin ring containing iron)

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97
Q

What is heme synthesis?

A

Creating of heme in the mitochondria and cytoplasm of NRBCs

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98
Q

Describe the pathway of heme synthesis

A

glycine + succinyl CoA —> delta ALA (by activation by Vitamin B6 and erythropoietin)
delta ALA —> porphobilinogen (by activation by ALA dehydrase)
porphobilinogen —> uroporphyrinogen III —> coproporphyrinogen III —> protoporphyrinogen IX —> protoporphyrin IX
protoporphyrin IX —> heme (ferroprotoporphyrin IX) (with iron by iron chelatase)

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99
Q

What would happen to heme synthesis if there is an iron deficiency?

A

Less heme would be formed in the NRBCs and protoporphyrin would accumulate

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100
Q

What would happen if there was a deficiency in enzymes that are required for heme synthesis?

A 
Less heme would be formed or would stop altogether at the point of deficiency
Other products (porphyrins) may be formed and cause diseases
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101
Q

What stimulates globin synthesis?

A

The presence of free heme in the cytoplasm of the NRBC

102
Q

Where does globin synthesis take place?

A

In the ribosomes of the NRBCs

103
Q

What are the 6 possible polypeptide chains in globin synthesis?

A

Alpha, beta, gamma, delta, epsilon, and zeta

104
Q

How is the golbin polypeptide chain decided?

A

Produced at different rates by mRNA depending on the person’s age

105
Q

How does heme bond to globin?

A

By the iron atom to two histidine sites on the globin

One is permanent one is reversible (used by O2 or H2O)

106
Q

What are the 3 types of embryonic hemoglobin?

A

Hb Gower 1 (E4 or Z2E4)
Hb Portland (Z2G2)
Hb Gower 2 (A2E2)

107
Q

What are the characteristic of embryonic hemoglobin?

A

Produced in first 12 weeks gestation

NO BETA CHAINS

108
Q

What is fetal hemoglobin?

A

HbF (A2G2)

109
Q

What are the characteristics of fetal hemoglobin?

A

Higher affinity for O2 (not good at letting O2 go)
Resists denaturation in alkalines and acids (lab tests)
>75% of hbg at birth is HbF
Not evenly distributed in all RBCs

110
Q

What are the 2 adult hemoglobins?

A

HbA2 (A2D2)

HbA (A2B2)

111
Q

What are the characteristic of adult hemoglobin A2?

A

<3% of total hgb
Evenly distributed
Same O2 affinity as A

112
Q

What are the characteristics of adult hemoglobin A?

A

Major component

96-98% of total hgb

113
Q

What polypeptide chain has the best oxygen carrying and delivering ability?

A

Alpha

Adult hgb always has 2 alpha chains

114
Q

What is hemoglobin A1C?

A

“Glycosylated/glycated hemoglobin”

Hemoglobin A and a glucose molecule attached to the beta polypeptide

115
Q

How is hemoglobin A1C testing used?

A

Used to monitor diabetes over a period of time

Normal person has <5%

116
Q

Define reduced hemoglobin

A

HbA in which iron atoms are in the ferrous (2+) state

Required state for binding oxygen

117
Q

Define oxyhemoglobin

A

HbO2

Reduced hemoglobin carrying O2 bound to some or all iron atoms

118
Q

Define deoxyhemoglobin

A

Reduced hb not carrying O2

119
Q

Define methemoglonin

A

MetHb/oxidized hemoglobin

Iron atoms are in the ferric (3+) state, cannot bind O2

120
Q

How does methemoglobin occur?

A

Peroxidases, oxidizing agents, certain drugs, chemicals, and gases
Oxidation overwhelms reduction systems, or reduction systems fail/are inhibited and can’t stop normal oxidation

121
Q

How does the body fight the creation of methemoglobin?

A

Strong reducing systems in the cells keep levels at less than 0.5% (>2% is abnormal)

122
Q

What does increased methemoglobin cause?

A

Hypoxia due to decreased O2 carrying capacity

123
Q

What might methemoglobinemia rarely be caused by?

A

Inherited production of abnormal HbM or from enzyme deficiency in reducing pathway

124
Q

Define carboxyhemoglobin

A

HbCO

HbA combined with carbon monoxide instead of oxygen

125
Q

How does carboxyhemoglobin occur? What happens to the patient?

A

Exposure to carbon monoxide
Affinity for CO is greater than O2, small amounts result in significant HbCO formation
Maraschino cherry red cyanosis develops in carbon monoxide poisoning

126
Q

Define sulfhemoglobin

A

sulfHb/verdoglobin
HbA + inorganic sulphides or H2O2
One S atom combines with Hb and a permanent covalent bond occurs

127
Q

What causes sulfhemoglobin?

A

Sulphur containing medicine, H2S gas, sulphur containing foods

128
Q

What do maturing nucleated red blood cells use their energy on?

A

Creating proteins for maturation and mitosis like hemoglobin, membrane proteins, and enzymes

129
Q

What do mature red blood cells use their energy on?

A
  1. Active transport (NaK pump, Ca pump), endergonic reactions (phosphorylation of glucose in glycolysis)
  2. reducing co-enzymes (NAD reduced to NADH reduced to NADPH)
130
Q

Where do red blood cells get their energy from?

A

2 pathways of glycolysis

  1. Embden-Meyerhof Pathway (anaerobin)
  2. Pentose Shunt Pathday (hexose-monophosphate shunt)
131
Q

What is formed in the embden-meyerhof pathway?

A

2 molecules of ATP (ADP+2Pi+glucose energy)

132
Q

How is ATP used in a red cell?

A

Active transport pumps (NaK, Ca)

Other endergonic reactions

133
Q

What is formed in the pentose shunt pathway?

A

1 NADPH molecule (NADH reduction)

134
Q

What is NADPH used for in a red cell?

A 
Reduced GSGG (oxidized glutathione) to GSH (reduced glutathione), which (with glutathione peroxidase) prevents oxidative damage to the cell by neutralizing oxidizers
Also metHb --> Hb with metHb reductase
135
Q

What happens if either glycolysis pathway activity is decreased?

A

Reduced NADH, NADPH, and ATP production leading to early hemolysis (death) due to membrane or enzyme damage and active transport failure

136
Q

What are the functions of RBCs?

A
  1. Oxygen transport
  2. Carbon dioxide transfer/hydrogen buffering
  3. Nitric oxide transport
137
Q

How do RBCs transport oxygen?

A

O2 binds to ferrous iron in hemoglobin (each heme binds 1 O2, so 4 O2 per hemoglobin)
Oxygenation is reversible

138
Q

Define oxygen saturation

What is the normal amount?

A

Amount of O2 carried by the hemoglobin in the blood, expressed as a percent of total capacity
ex: 90% = 90% of available sites are carrying O2

Normal arteriol = 95%
Normal venous = 75%

139
Q

Define partial pressure of oxygen

A

“Oxygen tension”
Amount of O2 in the plasma
ex: pO2 = 40mmHg

140
Q

What factors affect oxygen saturation?

A
  1. O2 availability (reduced O2)
  2. Reduced hemoglobin availability (abnormal Hb, reduced amount)
  3. Hb oxygen affinity (bonding attractiveness of O2 to Hb)
141
Q

What is high O2 affinity? Low O2 affinity?

A

High - Hb quickly and easily bind O2 and hang on (highest in lungs)
Low - Hb releases O2 and has more difficulty binding (lowest in tissues)

142
Q

How is O2 affinity determined?

A
  1. Heme-heme interaction (molecular structure changes)
  2. Temperature
  3. Bohr Effect (pH)
  4. 2, 3 Biphosphoglycerate (BPG)
143
Q

Define heme-heme interaction

A

“Cooperative binding”

As O2 molecules bind to Hb, the structure changes to increase the affinity

144
Q

How does temperature affect O2 affinity?

A

Increased temperature = decreased affinity (O2 released)

Decreased temperature = increased affinity (O2 bound)

145
Q

How does the Bohr Effect (pH) affect O2 affinity?

A

7.40pH is normal
pH decreases at tissues (7.36) decreasing affinity
pH increases at the lungs (7.44) increasing affinity

146
Q

What is 2, 3-BPG?

A

2, 3-biphosphoglycerate, a by-product of the embden-meyerhog pathway
Produced by red cells during hypoxia at the tissues

147
Q

How does 2, 3-BPG affect O2 affinity

A

2, 3-BPG (produced by the red cells) binds to Hb and changes its shape, decreasing affinity and releasing ALL O2
Called desaturation

148
Q

What are the axises on the O2 affinity curve?

A

X axis - pO2 (plasma concentration)

Y axis - O2 saturation (O2 on Hb)

149
Q

What factors would cause the O2 affinity curve to shift to the right? (less saturation)

A

Decreased pH, increased temperature, increased 2, 3-BPG

150
Q

What factors would cause the O2 affinity curve to shift to the left? (more saturation)

A

Increased pH, decreased temperature, decreased 2, 3-BPG

151
Q

What hemoglobin is associated with increased affinity? Decreased affinity?

A

Increased affinity = HbF

Decreased affinity = HbS (sickle cell)

152
Q

How does carbon dioxide transport work?

A

85% diffuses into the RBCs and is converted to HCO3 (bicabonate) and H+ by carbonic anhydrase and H2O
The H+ ions bind to negatively charged amino acids
The HCO3 diffuses out of the RBC into the plasma until equilibrium is reached

153
Q

What is the buffering action of hemoglobin?

A

When the H+ created with CO2 becomes HCO3 in the RBC, it attaches to negatively charged amino acids in the hemoglobin which prevents it from accumulating and decreasing the pH

154
Q

What is the chloride shift?

A

When HCO3 diffuses out of the RBCs chloride ions usually follow it to balance the electrical charge

155
Q

What happens to the 15% of CO2 that does not get converted to HCO3?

A

10% is carried as carbamino hemoglobin bound to globin amino acids
5% is carried in the plasma as gas

156
Q

What is nitric oxide?

A

Vessel dilator, muscle relaxant produced by endothelial cells to maintain vascular patency (dilation) and resist platelet adhesion

157
Q

How is nitric oxide transported?

A

It attaches to free iron atoms in the heme and is carried from the tissues to the lungs
Thought to be released when oxygen tension is low, causing vasodilation and increased blood flow, and the opposite in high oxygen tension

158
Q

What is super nitric oxide? How is it transported?

A

Nitric oxide with an extra electron

Attaches to cystine in the globin polypeptides and moves from the lungs to the tissue

159
Q

How are old RBCs removed from circulation?

A

Extravascularly - macrophages in the liver sinusoids and spleen
Intravasculrly - (small amount) hemolysed by hard collisions

160
Q

What is extravascular hemolysis?

A

Occuring outside of the bloodstream, usually the liver and spleen

161
Q

What happens when an RBC is phagocytised?

A

Useful parts are stored or released into circulation

Non-usable portions are excreted by the liver or kidneys

162
Q

How does hemoglobin catabolism work?

A

Hb is digested by lysozymes in the macrophages by:

  1. heme detached from globin
  2. globin hydrolyzed to amino acids
  3. iron detached from protoporphyrin and stored (bound to apoferritin as ferritin) or moved into plasma bound to transferrin
  4. protoporphyrin oxidized to biliverdin, releasing CO, and moved into plasma and reduced to indirect bilirubin
163
Q

What happens to unconjugated bilirubin in the blood?

A

Bound by albumin and brought to liver
Albumin attaches to Kupffer cells (macrophages)
Bilirubin is pinocytosed and conjugated

164
Q

What happens to bilirubin after it is conjugated in the liver?

A

Moves into bile ducts then gallbladder

Released into the duodenum and is reduced by bacteria to urobilinogen and stercobilinogen

165
Q

What happens to urobilinogen in the duodenum?

A

Some is reabsorbed and returned to the liver, then makes its way back
Most is converted to urobilin, stercobilin, and mesobilin and excreted

166
Q

What happens if extravascular hemolysis is increased?

A

Increased hemoglobin catabolism, increased waste

Hyperbilirubinemia, increased urine urobilinogen, increased CO

167
Q

What may cause hyperbilirubinemia?

A

Increased extravascular hemolysis
Liver disease/failure, cannot conjugate properly (increased indirect)
Bile duct obstruction, cannot get rid of bilirubin (increased direct)

168
Q

What is intravascular hemolysis?

A

Hemolysis of RBCs in the blood stream

169
Q

What happens in intravascular hemolysis?

A

Hemoglobin is released into the plasma and is bound by haptoglobin
The complex is pinocytosed by macrophages in the liver and spleen
Catabolism occurs the same way as in extravascular hemolysis

170
Q

What happens if there is increased intravascular hemolysis?

A

Hemoglobinemia, haptoglobin might be used up

171
Q

What happens if there is not enough haptoglobin to bind hemoglobin in the plasma?

A

Hemoglobin dissociates into heme and globin, heme oxidizes to metheme and binds to albumin (methemalbumin) causing methemalbuminemia (brown plasma)
or
Hemoglobin dissociates into dimers, excreted by the glomerulus and excreted in urine (hemoglobinuria)
Some is absorbed by the renal tubular cells and iron is stored as hemosiderin, killing the cells, and shedding into the urine (hemosiderinuria)

172
Q

What are signs of increased intravascular hemolysis?

A 
Hemoglobinemia
Decreased haptoglobin
Methemalbuminemia
Hemoglobinuria
Hemosiderinuria
173
Q

Explain the difference between medullary hematopoiesis and extra-medullary hematopoiesis

A

Medullary - production of myeloid cells in bone marrow

Extramedullary - production of myeloid cells outside bone marrow, in liver and spleen

174
Q

Which of the normal blood cells is a non-myleoid cell?

A

Lymphocytes

175
Q

Which of the myeloid cells is found only in the marrow? Why?

A

Megakaryocytes because the cytoplasm disintegrates into platelets in the marrow

176
Q

Blood cells are of epithelial origin

a. true
b. false

A

b. false

Mesodermal and connective tissue origin

177
Q

The heart develops before the bones

a. true
b. false

A

a. true

178
Q

The liver assumes main responsibility for production of blood cells after the seventh month of gestation

a. true
b. false

A

b. false

The liver does this after the sixth week of gestation

179
Q

In infants and children up to 10 years of age, nearly all of the bone marrow is active (yellow)

a. true
b. false

A

b. false

It is active, but it is red not yellow. Yellow marrow is fatty and inactive

180
Q

What are the names and duration of each of the major phases of hematopoiesis in the embryo, fetus and adult?

A

Embryo - mesoblastic, 2-12 weeks gestation
Fetus - hepatic, 6th week gestation - 2 weeks old
Adult - myeloid, 20th week gestation to death

181
Q

Name the cell described:

Can become any connective tissue cell

A

Reticulum cell

182
Q

Name the cell described:

The blast cell of a neutrophil

A

Myeloblast

183
Q

Name the cell described:

Committed to become any myeloid cell

A

CFU-GEMM

184
Q

Name the cell described:

The largest hematopoietis cell

A

Megakaryocyte

185
Q

In hemtopoiesis what is responsible for the mitosis of blast cells?

A

The bone marrow environment

186
Q

In hematopoiesis what is responsible for the differentiation of blast cells?

A

Specific growth hormones

187
Q

For a developing series of blood cells, describe the usual morphologic changes that occurin the marrow from blast to mature forms:

In cell size
In nuclear chromatin clumping
In color of cytoplasm

A

They get smaller
It gets more clumped or condensed
Blue basophilia of the blast cell to colors that reflect the changing contents of the cytoplasm of mature cells

188
Q

What is meant by nuclear cytoplasmic asynchrony?

A

The nucleus or the cytoplasm develops faster or slower than normal

189
Q

What is ineffective erythropoiesis?

A

More than 15% of the red cells developing in the marrow die before release into the blood

190
Q

Name stromal cells in the bone marrow

A

Fibroblasts, endothelial cells

191
Q

Name 4 immediate progeny of the CFU-GEMM

A

BFU-E
CFU-meg
CFU-GMEo
CFU-baso

192
Q

Define a blast cell

A

Earliest for of a blood cell that is morphologically recognizable by physical appearance as belonging to a specific cell line

193
Q

What kinds of cells secrete cytokines?

A

Lymphocytes, macrophages, bone marrow stromal cells

194
Q

List the secretor cell(s) and function(s) of the following cytokine:

IL-1

A

Macrophages

Activates and induces cytokine production by T cells and marrow stromal cells

195
Q

List the secretor cell(s) and function(s) of the following cytokine:

IL-3

A

T lymphocytes

Induces maturation and mitosis of CFU-S in synergy with SCF, Flt-L

196
Q

List the secretor cell(s) and function(s) of the following cytokine:

GM-CSF

A

Marrow stromal cells
Induces maturation and mitosis of CFU-GEMM, CFU-GMEo, CFU-GM, and CFU-base
Activates phagocytic and killing functions of neutrophils and macrophages

197
Q

List the secretor cell(s) and function(s) of the following cytokine:

IL-5

A

Marrow stromal cells

Induces eosinophil growth and function

198
Q

List the secretor cell(s) and function(s) of the following cytokine:

EPO

A

Kidney cells

Induces maturation and mitosis of the erythroid cell line

199
Q

List the secretor cell(s) and function(s) of the following cytokine:

TPO

A

Liver cells

Induces maturation and endomitosis of megakaryoblasts

200
Q

What is the most important property of the erythrocyte plasma membrane?

A

Selective permeability

201
Q

Briefly describe the sodium pump

A

ATP is used to move Na out of and K into the cell against concentration gradients to maintain necessary intracellular concentrations of ions

202
Q

What part(s) of the erythrocyte plasma membrane may act as antigens?

A

Glycoproteins, glycolipids

203
Q

What part(s) of the erythrocyte plasma membrane maintain the shape of the cell?

A

Actin and spectrin

204
Q

What part(s) of the erythrocyte plasma membrane are lipids?

A

Phospholipids and cholesterol

205
Q

What is a concentration gradient?

A

A difference in concentration of substances across a membrane

206
Q

What is the specific site of synthesis of heme?

A

Mitochondria

207
Q

What is the specific site of synthesis of globin?

A

Ribosomes

208
Q

Why is hemoglobin not synthesized in mature erythrocytes?

A

They have no nucleus to make mRNA and they have no ribosomes to make the polypeptides from mRNA if they had any

209
Q

In the first reaction in the synthesis of heme name the reactants

A

Glycine and succinyl-CoA

210
Q

In the first reaction in the synthesis of heme name the reaction product

A

Delta-aminolevulinic acid

211
Q

In the first reaction in the synthesis of heme name the reaction enzyme

A

Delta-aminolevulinic acid synthetase

212
Q

In the first reaction in the synthesis of heme name the reaction coenzyme

A

Pyridoxine (Vitamin B12)

213
Q

In the first reaction in the synthesis of heme name the enzyme activator

A

Erythropoietin

214
Q

In the first reaction in the synthesis of heme name the reaction inhibitor

A

Heme

215
Q

If any of the enzymes in the reactions leading to the formation of heme are deficient or absent, then _____ accumulates in the red cells and other tissues, causing a disease called _____

A

Porphyrins

Porphyria

216
Q

What are the symbols and Greek names for the six types of polypeptide chains that form the various globins during the lifetime of a normal individual (from fetus to adult)

A

Alpha, beta, gamma, delta, epsilon, zeta

217
Q

A normal hemoglobin molecule contains ____ heme molecules, globin(s), and ____ polypeptides making up each globin

A

Four

Four

218
Q

Hb Gower is found in the embryo, fetus, and adult

a. True
b. False

A

b. false

Embryo only

219
Q

Hb F is also called female hemoglobin

a. True
b. False

A

b. false

Fetal hemoglobin

220
Q

HbA2 is the major component of adult Hb

a. True
b. False

A

b. false

Minor component

221
Q

Alpha polypeptide chains are found in all types of normal adult hemoglobin

a. True
b. False

A

a. true

222
Q

Alpha2Delta2 is the polypeptide formula for HbA2

a. True
b. False

A

a. true

223
Q

Reduced hemoglobin contains iron atoms in the ferrrous state

a. True
b. False

A

a. true

224
Q

Write out the full name for NAD and NADPH

A

Nicotinamide adenine dinucleotide

Nicotinamide adenine dinucleotide phosphate

225
Q

Methemoglobinemia represents a condition in the blood where more than ____% of total Hb is metHb

A

2%

226
Q

Methemoglobin is oxidized Hb

a. True
b. False

A

a. true

227
Q

Methemoglobin is irreversible

a. True
b. False

A

b. false

228
Q

Methemoglobin carries oxygen

a. True
b. False

A

b. false

229
Q

Methemoglobin contains low ferric iron

A

a. true

230
Q

What are 2 types of reduced HbA and how are they different from one another?

A

Oxyhemoglobin - reduced Hb that can and is carrying oxygen

Deoxyhemoglobin - reduced hemoglobin that can, but is not carrying oxygen

231
Q

Which type of Hb results from binding a sulphur into the molecule?

A

Sulfhemoglobin

232
Q

Which type of Hb results from binding carbon monoxide into the molecule?

A

Carboxyhemoglobin

233
Q

Which type of Hb results from binding carbon dioxide into the molecule?

A

Carbinohemoglobin

234
Q

Which type of Hb results from binding oxygen into the molecule?

A

Oxyhemoglobin

235
Q

Which energy pathways are lost after the RBC extrudes its nucleus and other unnecessary cellular organelles?

A

The Kreb’s cycle and the electron transport system

236
Q

Mature red cells use the Embden-Meyerhof pathway of reactions to produce _____ and _____

A

NADH and ATP

237
Q

Mature red cells use the pentose shut to produce _____

A

NADPH

238
Q

How does NADPH prevent oxidation of cellular proteins?

A

Reduces glutathione, which reduces oxidizing agents in the cell

239
Q

What two cellular compounds (produced by glycolysis) are used to reduce metHb

A

NADH and NADPH

240
Q

What is 2, 3-BPG, how is it produced, and what does it do?

A

2, 3-Biphosphoglycerate
Produced in a small pathway off the Embden-Meyerhof pathway called the Rapport-Leubering Shunt
Binds with Hb in red cells and forces dissociation of O2 (desaturation)

241
Q

How does oxygenation differ from oxidation?

A

Oxygenation - binding and release of oxygen without gain or loss of electrons
Oxidation - loss of electrons in a reaction

242
Q

What is the oxygen affinity of hemoglobin? What 4 factors influence affinity in the red cell?

A

Oxygen affinity is the chemical bonding attractiveness of oxygen to Hb

  1. pH
  2. Temperature
  3. 2,3-BPG
  4. Number of oxygen atoms already bound (heme-heme interaction)
243
Q

Briefly outline the effects of increasing and decreasing pH on the oxygen affinity of hemoglobin

A

pH increases, oxygen affinity also increases

pH decreases, oxygen affinity also decreases

244
Q

What component of hemoglobin binds oxygen at the lungs and carries it to the tissues?

A

The iron atoms in the heme

245
Q

What are the 3 ways in which CO2 formed in the tissues is carried to the lungs?

A
  1. As HCO3
  2. As carbaminohemoglobin
  3. As a dissolved gas in the plasma
246
Q

What enzyme is responsible for catalyzing the reactions that result in the transport of the great majority of CO2 by the red cells?

A

Carbonic anhydrase

247
Q

What are the two types of hemolysis that destroy about 10 billion erythrocytes per hour in the average person and where does each type of hemolysis occur?

A

Extravascular - by the sinusoidal mononuclear phagocytes of the liver and spleen
Intravascular - hemolysis in circulation

248
Q

The only physiologic reaction that produces carbon monoxide occurs in the catabolism of hemoglobin by reticuloendothelial macrophages. What is the reaction?

A

The catabolism of protoporphyrin IX into biliverdin

249
Q

Differentiate direct from indirect bilirubin

A

Direct - conjugated with one or two molecules of glucuronic acid
Indirect - not conjugated with glucuronic acid

250
Q

If there is a great deal of abnormal hemolysis, list some lab findings if the hemolysis occurs extravascularly

A

Increased plasma bilirubin
Increased urobilinogen in urine
Increased CO in expired air

251
Q

If there is a great deal of abnormal hemolysis, list some lab findings if the hemolysis occurs intravascularly

A 
Hemoglobinemia
Decreased plasma haptoglobin
Hemoglobinuria
Methemalbuminemia
Hemosinderinuria

Hematology 1 (4 decks)

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