Module 1: Normal Blood Components, Production, and Erythrocytes Flashcards
(158 cards)
1
Q
What is hematopoiesis?
A
The production and development of blood cells, characterized by the constant restoring of the various cells of the blood
2
Q
Name the parts of the hematopoietic system
A
bone marrow, liver, spleen, thymus, and lymph nodes
3
Q
What does erythropoiesis produce?
A
Erythrocytes (red blood cells)
4
Q
What does leukopoiesis produce?
A
Leukocytes (white blood cells)
5
Q
What does thrombopoiesis produce?
A
Thrombocytes (platelets)
6
Q
Name the 5 type of luekocytes
A
Granulocytes (have visible granules):
- neutophils
- eosinophils
- basophils
- monocytes
- lymphocytes (t cells and b cells)
7
Q
What is a myeloid cell? What blood cells are myeloid cells?
A
Myloid cells are produced and differentiate in the bone marrow (red only). The cells are erthyrocytes, platelets, neutrophils, eosinophils, basophils, and monocytes. *everything except lymphocytes!
8
Q
What is a non-myeloid cell? What blood cell is the only non-myeloid cell?
A
Non-myeloid cells are produced and differentiate outside of the bone marrow. Lymphocytes are the only non-myeloid cells.
9
Q
Define medullary hematopoiests
A
The production of blood cells (myeloid cells) in the bone marrow
10
Q
Define extra-meduallry hematopoiesis
A
The production of myeloid cells outside the bone marrow. Usually in the spleen and/or liver. *This is not normal in adults
11
Q
When does blood cell production start in the human body?
A
At about 2 weeks gestation
12
Q
What happens in the mesoblastic phase of hematopoiesis? How long does it last?
A
Occurs during the 2nd to 12th week of gestation. During this time the yolk sac and embryo produce primitive blood stem cells, called erythroblasts.
13
Q
When do blood vessels and the heart start circulation blood in the human body?
A
By the end of the 4th week of gestation, which is during the mesoblastic phase
14
Q
What happens in the hepatic phase of hematopoiesis? How long does it last?
A
Occurs during the 6th week of gestation to around two weeks after birth. The liver and spleen produce more mature erythrocytes: first granulocytes, then monocytes. The lymph nodes produce lymphocytes. The bones and bone marrow begin forming at the 8th week of gestation.
15
Q
What happens in the myeloid phase of hematopoiesis? How long does it last?
A
Occurs from the 20th week of gestation until death. Lymph nodes continue producing lymphocytes. All other blood cells, myeloid cells, are produced by the red bone marrow. The liver and spleen still have the potential for hematopoiesis if necessary.
16
Q
What is red bone marrow?
A
Active bone marrow that produces blood cells
17
Q
What is yellow bone marrow?
A
Inactive bone marrow that is mostly fat. Very little hematopoiesis occurs.
18
Q
Where is red bone marrow located in adults?
A
- The anterior and posterior iliac crests of the pelvis (hip bones)
- Sternum
- Proximal ends of the long bones
- Vertebrae
- Skull
19
Q
Where are non-myeloid cells produced?
A
Lymph nodes and other lymphatic tissue such as the liver, spleen, and tonsils
20
Q
What connective cell tissues are found in the bone marrow?
A
Fibroblasts (collagen, elastin, reticular protein), endothelial cells, blood cells, blood vessels, and nerves
21
Q
What is the growth environment of the bone marrow sometimes called?
A
Hematopoietic Inductive Microenvironment (HIM)
22
Q
When does the liver become involved with hematopoiesis?
A
The 2nd trimester. It becomes the principle site of cell production
23
Q
What does the spleen do during the myeloid stage of hematopoiesis?
A
It is involved in the removal of old and damaged red cells and storing platelets. It is also the largest lymphoid organ
24
Q
What does the thymus do in hematopoiesis?
A
It is involved with the production and maturation of T-lymphocytes (T-cells)
25
What do lymph nodes do in hematopoiesis?
They are involved with the formation of new lymphocytes
26
What are stem cells?
Primitive, formative, unspecialized blood cells. They have the potential to change into several types of more specialized offspring
27
What is the first, most primitive stem cell associated with hematopoiesis?
The reticulum cell
28
What does the reticulum cell specialize into?
The CFU-S (Colony forming unit -stem)
29
Describe the CFU-S (Colony forming unit - stem)
They are also known as pluripotential blood stem cells and multipotent lymphohematopoietic stem cells. They are partially differentiated.
30
What can a CFU-S (Colony forming unit - stem) differentiate into?
Either a CFU-L (colony forming unti - lymphoid) or a CFU-GEMM (colony forming unit - granulocyte, erythroid, monocyte, megakaryocyte)
31
What can a CFU-L (colony forming unit - lymphoid) differentiate into?
Various levels of lymphocyte precursors, including T and B lymphoblasts and NK (natural killer) cells
32
What can a CFU-GEMM (colony forming unit - granulocyte, erythroid, monocyte, megakaryocte) differentiate into?
- CFU-Eo (eosinophil)
- CFU-baso (basophil)
- CFU-GM (granulocyte, monocyte)
- CFU-G (granulocyte)
- CFU-M (monocyte)
- BFU-E (burs forming unit - erythroid)
- CFU-E (erythroid)
- BFU-meg (burst forming unit - megakaryocyte)
- CFU-meg (megakaryocyte)
33
What is a blast cell?
The earliest stage of a blood cell that can be visually recognized as the precursor to a particular cell line
34
Name all the blast cells
- pronormoblast (erythrocyte)
- megakaryoblast (megakaryocyte/platelet)
- monoblast (monocyte)
- myeloblast (neutrophil)
- lymphoblast (lymphocyte)
35
What two cells do not have a specific blast phase?
Eosinophils and basophils
36
Would blast cells ever be seen in the peripheral blood?
No, unless there was a serious disorder
37
What are growth factors?
Proteins that bind to receptors on cells surfaces, resulting in activation of cellular proliferation/maturation
38
What are cytokines?
The most important growth factors in regards to hematopoiesis. They are chemical mediators that are secreted locally and affect their target cells
39
Name the growth factors secreted by macrophages, lymphocytes, and bone marrow stromal cells (ie: fibroblasts, endothelial cells)
Colony stimulating factors (CSF) and interleukins (IL)
40
What cells secrete CSF and IL's?
Macrophages, lymphocytes, and bone marrow stromal cells (fibroblasts, endothelial cells)
41
Name the growth factors that are secreted by the kidneys
Erythropoietin (EPO)
42
What secretes EPO?
The kidneys
43
Name the growth factors secreted by the liver
Thrombopoietin (TPO)
44
What secretes TPO?
The liver
45
What is a monokine?
A cytokine produced by macrophages
46
What is a lymphokine?
A cytokine produced by lymphocytes
47
Outline the phases in the production of erythrocytes
1. Reticulum cell
2. CFU-S
3. CFU-GEMM
4. BFU-E
5. CFU-E
6. Pronormoblast
7. Erythrocyte
48
Outline the phases in the production of thrombocytes
1. Reticulum cell
2. CFU-S
3. CFU-GEMM
4. BFU-meg
5. CFU-meg
6. Megakaryoblast
7. Thrombocyte
49
Outline the phases in the production of monocytes
1. Reticulum cell
2. CFU-S
3. CFU-GEMM
4. CFU-GM
5. CFU-M
6. Monoblast
7. Monocyte
50
Outline the phases in the production of neutrophils
1. Reticulum cell
2. CFU-S
3. CFU-GEMM
4. CFU-GM
5. CFU-G
6. Myeloblast
7. Neutrophil
51
Outline the phases in the production of euosinophils
1. Reticulum cell
2. CFU-S
3. CFU-GEMM
4. CFU-Eo
5. Eosinophil
52
Outline the phases in the production of basophils
1. Reticulum cell
2. CFU-S
3. CFU-GEMM
4. CU-baso
5. Basophil
53
Outline the phases in the process of lymphocytes
1. Reticulum cell
2. CFU-S
3. CFU-L
4. Lymphoblast
5. Lymphocyte (T-cell, B-cell, NK)
54
What produces tissue necrosis factor and interleukin-1?
Monocytes and macrophages
55
What do tissue necrosis factor and interleukin-1 do?
Activate and stimulate cytokin production in lymphocytes and bone marrow stromal cells
56
What produces stem cell factor, flt ligand, interleukin-3, and interleukin-5?
Lymphocytes
57
What do stem cell factor, flt ligand, and interleukin-3 do together?
Induce differentiation and mitosis of CFU-S into CFU-GEMM or CFU-L cells
58
What does interleukin-5 do?
Induces eosinophil growth and function
59
What produces granulocyte/monocyte stimulating factor, ganulocyte (neutrophil) stimulating factor, and monocyte/macrophage stimulating factor?
The bone marrow stromal cells
60
What does granulocyte/monocyte stimulating factor do?
Induces differentiation and mitosis of CFU-GEMM into committed stem cells. Also stimulates phagocytic and cytotoxic functions of neutrophils and macrophages
61
What does granulocyte (neutrophil) stimulating factor do?
Induces maturation and mitosis of CFU-G and myeloblasts
62
What does monocyte/macrophage stimulating factor do?
Induces maturation and mitosis of CFU-M and monoblast cells
63
What produces erythropoietin?
Kidney cells
64
What does erythropoietin do?
Induces maturation and mitosis of BFU-E, CFU-E, and pronormoblast, and developing NRBC cells. Induces increased production of other myeloid cells
65
What produces thrombopoietin?
Liver cells
66
What does thrombopoietin do?
Induces maturation and mitosis of CFU-meg, and megakaryoblast cells
67
Define effective hematopoiesis
When 85% or more of the red blood cells formed in the bone marrow are released successfully. So 15% or less of them die before they are released
68
Define ineffective hematopoiesis
When 15% of them die before being released
69
How long to erythroid normoblasts (NRBC)'s survive in each of the following locations of the body:
- bone marrow
- peripheral blood
- tissues
5 days, 0 days (do not reach blood stream), 0 days (do not reach tissues)
70
How long do reticulocytes survive in each of the following locations of the body:
- bone marrow
- peripheral blood
- tissues
3 days, 1 day, 0 days (do not reach tissues)
71
How long do fully formed erythrocytes survive in each of the following locations of the body:
- bone marrow
- peripheral blood
- tissues
1 day, 110-120 days, 0 days
72
How long do megakaryocytes survive in the following locations of the body:
- bone marrow
- peripheral blood
- tissues
7 days, 0 days (never reach blood stream), 0 days (do not reach tissues)
73
How long do fully formed platelets survive in the following locations of the body:
- bone marrow
- peripheral blood
- tissues
0 days, 8-10 days, 0 days
74
How long do immature neutrophils survive in each of the following locations of the body:
- bone marrow
- peripheral blood
- tissues
5 days, 0 days, 0 days
75
How long to fully formed neutrophils survive in each of the following locations of the body:
- bone marrow
- peripheral blood
- tissues
7 days, 8 hours, up to 6 days
76
How can the bone marrow increase cell production when demand for blood cells is increased? (4 ways)
1. release immature cells into blood stream (shift left 1 step)
2. increase the number of mitosis divisions in developing cells
3. decreasing maturation time/increasing maturation speed
4. expand hematopoiesis into inactive areas (extra-medullary hematopoiesis)
77
Define amplification
When many mature cells are produced from one immature cell (usually a blast cell) by many cell divisions and differentiations
78
List the 4 general morphologic features seen in all blood cells during maturation
1. changes in cell size
2. changes in nuclear/cytoplasmic ratio
3. changes in the nucleus
4. changes in the cytoplasm
79
What changes occur to the cell size during maturation?
Cell size progressively decreases
80
What changes occur to the cell's nuclear/cytoplasmic ratio during maturation?
Cytoplasm and nucleus decrease in size at the same time, but the nucleus shrinks faster, so the ratio decreases
81
What changes occur to the cell's nucleus during maturation?
The size of the nucleus decreases, and it loses it's nucleoli. Increased clumping and coarseness of the chromatin occurs as does increasingly dark staining of the nucleus. It is eventually lost/spit out
82
What changes occur to the cell's cytoplasm during maturation?
A decrease in volume occurs. It changes color from blue to blue/gray or pink
83
Define N/C asynchrony/dyspoiesis
When developments of the cell are "out of sync", either nucleus or cytoplasm shrinking lag behind the other. Usually suggests a metabolic disorder
84
List the steps in the maturation of nucleated red blood cells
1. Pronormoblast (rubriblast)
2. Basophillic normoblast (prorubricyte)
3. Polychromatic normoblast (rubricyte)
4. Orthochromic normoblast (metarubricyte)
5. Polychromatophillic (reticulocyte)
6. Erythrocyte
85
Describe the pronormoblast (rubriblast)
- size: 14-24 micrometers
- has a nucleus that is large and round, unclumped chromtin, 0-2 nucleoli
- N/C = 8:1 to 6:1
- cytoplasm is small, deep blue, and has no granules
86
Describe the basophilic normoblast (prorubricyte)
- size: 12-17 micrometers
- has nucleus that is round, slightly coarser chromatin clumping, parachromatin, nucleoli not visible
- N/C = 6:1 to 4:1
- cytoplasm still small, deep blue or purple, no granules
87
Describe the polychromatic normoblast (rubricyte)
- size: 10-15 micrometers
- has nucleus that is round, deep purple/black, heavily condensed chromatin, parachromatin, no nucleoli
- N/C = 4:1 to 2:1
- cytoplasm decreased but increased relative to nucleus, polychromatic, no granules
88
Describe the orthochromic normoblast (metarubricyte)
- size: 8-12 micrometers
- has nucleus that is round, pyknotic (very dense), black/brown color, not chromatin structure
- N/C = 1:1 to 2:1
- cytoplasm moderate, bluish-pink, no granules
89
Describe the polychromatophillic (reticulocyte)
- size: 7-10 micrometers
- no nucleus, extruded
- no N/C
- cytoplasm clear gray-blue, polychromatic to pink
90
Describe the erythrocyte
- size: 7-8 micrometers
- no nucleus
- no N/C
- cytoplasm is pink
91
Describe the red blood cell's plasma membrane
It is bilaminar and surrounds the cytoplasm. It is a double bipolar layer.
92
Name the main parts of the red blood cell's plasma membrane
- structural and contractile proteins actin and spectrin
- ATP'ase enzymes
- surface antigens: glycosphingolipids such as A, B, H blood group antigens and glycoproteins such as M, N antigens
- receptor protein molecules such as transferrin receptor (TfR)
93
What percentage is each part of the composition of the plasma membrane?
50% protein, 40% lipid (24% phospholipid, 12% cholesterol, 4% glycolipid), and 10% carbohydrate
94
What does the lipid in the plasma membrane do?
Glycolipids and phospholipids are arranged in two layers with polar group on the outside and inside surfaces, and non-polar groups in the center. Glycolipids act as antigens on the outer surface
95
What does the protein in the plasma membrane do?
Structural proteins are integral and penetrate through the membrane or are peripheral and attach to the inside or outside surface where they act as antigens.
Spectrin and actin help maintain the biconcave disk shape.
Band 3 protein acts and a channel to move ions in and out.
96
Why is the plasma membrane sometimes called a fluid mosaic?
The lipids of some of the integral proteins can move around the membrane within areas enclosed by spectrin/actin network
97
What do carbohydrates in the plasma membrane do?
They are found in a thin mucopolysaccaride layer on the exterior surface and as oligosaccharides that attach to lipids and proteins. Contribute to antigenic properties
98
What are the functions of the plasma membrane?
Selective permeability, the ability to selectively allow molecules to move in and out across the membrane.
99
What are the types of transport across the membrane?
Diffusion, facilitated diffusion, and active transport
100
Describe diffusion
Water and other small, lipid-soluble molecules cross the membrane in response to concentration and electrical gradients
101
Describe facilitated diffusion
Some molecules move through the membrane by attaching themselves to special transport molecules in the membrane
102
Describe active transport
Movement of molecules across the membrane against concentration and electrical gradients. Requires transport enzymes and energy (ATP)
103
Describe the sodium-potassium pump
Na+ moves in and K+ moves out by diffusion. The Na-K pump moves 2 molecules of K+ in and 3 molecules of Na+ out using 1 molecule of ATP. Thus the cell has a high concentration of K+ and low concentration of Na+
104
Describe the calcium pump
Calcium accumulates in RBC's and makes it less elastic. The Ca2+ pump moves calcium out with energy provided by ATP
105
Why do red cell membranes carry a negative charge?
This makes the RBC's repel each other and helps protect them from damage by softening the collisions they make with each other
106
What happens if ATP is unavailable to power the active transport mechanisms?
The mechanisms will slow down or fail. Na+ moves back in to the cell, followed by water, causing swelling and the loss of the biconcave shape. Ca2+ builds up and the cell loses flexibility.
This leads to hemolysis
107
What is the RBC's cytoplasm made up of?
90% hemoglobin and 10% other organelles, enzymes, electrolytes, carbohydrates, lipids, and proteins
108
How do mature RBC's have enough energy to function for 120 days in the blood stream?
Developing normoblasts synthesize enzymes, anti-oxidants, and coenzymes, and about 250 hemoglobin molecules
109
When is hemoglobin made?
65% of it is made in the developing normoblasts, and 35% is made in the polychomatophillic erythrocytes (reticulocyte)
110
What does hemoglobin production rely on?
Adequate iron supply and on synchronized production of heme and globin molecules in the cell
111
What is hemoglobin composed of?
Globin protein, composed of 4 polypeptide chains AND four heme molecules attached to one of the globin polypeptides
112
What is the first part of hemoglobin production?
Heme synthsis
113
Where is the heme synthesized?
The mitochondira and cytoplasm of the developing NRBC's and reticuloytes
114
The first two steps of heme synthesis, that occur in the mitochondria are:
1. glycine + succinyl CoA
2. added with Vitamin B6 (coenzyme), HEME, ALA synthetase, and EPO
Produces ALA
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The steps of heme synthesis that occur in the cytoplasm are:
1. ALA + ALA dehydrase
Produces porphobilinogen
2. Porphobilinogen + ALA dehydrase
Produces uroporphytinogen III
116
The last steps of heme synthesis that occurs in the mithochondia are:
```
1. Uroporphytinogen III + ALA dehydrase
Produces coproporphyrinogen III
2. Coproporphyrinogen III + ALA dehydrase
Produces protoporphyrinogen IX
3. Protoporphyinogen IX + ALA dehydrase
Produces protoporphyrin IX
```
***4. Protoporphyrin IX + Iron (Fe2+) and iron chelatase
Procudes: ***HEME (ferroprotoporphyrin IX)
117
If iron if deficient what happens to heme production?
Less heme is formed and protoporphyrin IX accumulates in excess
118
If any of the enzymes are deficient or inhibited what happens to heme production?
Synthesis decreases or shuts down at that point in the sequence and other products are formed and accumulate and cause disease
119
What stimulates the production of globin?
The presence of free heme in the cytoplasm of developing NRBC's
120
Where does globin production take place?
The ribosomes
121
What are the types of amino acids that can form globin's polypeptide chains?
Alpha, beta, delta, epsilon, gamma, and zeta
122
How does heme join with globin?
One heme bonds by its iron atom to two specific histidine sites. One bond is permanent and the other is reversible
123
How many hemes are there in a hemoglobin molecule?
Four identical hemes
124
How to hemoglobins vary?
Only by the types of polypeptide chains present
125
List the three embryonic hemoglobins and their polypeptide formula
- Hb Gower 1: epsilon four OR zeta two epsilon two
- Hb Portland: zeta two gamma two
- Hb Gower 2: alpha two epsilon two
126
What are the characteristics of the three embryonic hemoglobins?
They are produced in the first 12 weeks of gestation in the embryo and early fetus. There is no actual oxygen delivery
127
List the name and polypeptide formula of fetal hemoglobin
Hb F: alpha two gamma two
128
What are the characteristic of fetal hemoglobin?
At birth Hb F is >75% of total hemoglobin
| Adults have
129
List the two types of adult hemoglobin and their polypeptide formulas
HbA: alpha two beta two
HbA2: alpha two delta two
130
What are the characteristics of adult hemoglobin A?
The most major component, usually 96-98% of hemoglobin
131
What are the characteristic of adult hemoglobin A2?
Minor component,
132
What is HbA1c?
HbA plus a molecule of glucose attached to the beta polypeptides. Usually accounts for
133
Define reduced hemoglobin
HbA where iron is in the ferrous state (Fe2+).
| **Ferrous state is required for oxygen binding
134
Define oxyhemoglobin (HbO2)
Reduced HbA that is carrying O2 bound to some or all of the iron atoms of the hemes
135
Define deoxyhemoglobin
Reduced HbA that is not carrying any O2
136
Define methemoglobin (MetHb)/oxidized hemoglobin
HbA where iron is in ferric state (Fe3+). Cannot bind oxygen.
137
What promotes the formation of MetHb?
Peroxides and other oxidizing agents, but it is usually reduced to a very small concentation (
138
Define hypoxia
Cells starved of oxygen
139
How does MetHb form in excess?
Excessive oxidation or reducing system failure/inhibition. Results in hypoxia
140
Define carboxyhemoglobin (HbCO)
HbA combining with carbon monoxide. HbA has a higher affinity for CO
141
Define sulfhemoglobin (sulfHb)
HbA reaction with soluble, inorganic sulphides and H2O2. One S atom binding with Hb is irreversible and prevents O2 binding
142
What is energy used for in developing NRBC's?
Synthesis of proteins for maturation and mitosis, ie: hemoglobin, membrane proteins, and enzymes for glycolysis
143
What is energy used for in mature RBC's?
```
Active transport (Na+, K+, Ca2+), other endergonic reactions
Reducing coenzymes NADH and NADPH
```
144
How does the RBC get energy?
Glycolysis, the release of energy and electrons from glucose. Energy is stored in the phosphate bonds of ATP and electrons reduce coenzymes
145
Name the 2 pathways that produce energy for the RBC
Embden-Meyerhof pathway
| Pentose Shunt Pathway
146
What does the Embden-Meyerhof pathway do?
80-90% of glucose metabolized to lactate.
1. Each molecule of glucose that enters produces 2 molecules of ATP
2. Reduction of NAD produces 2 molecules of NADH
147
What does NADH do?
A source of electrons to allow the enzyme methemoglobin reductase to convert methemoglobin into reduced hemoglobin
148
What does the Pentose Shunt pathway do?
5-10% of glucose is oxidized here.
| 1. For each glucose molecule one molecules of NADPH is produced by the reduction of NADH
149
What does NADPH do?
Used by the enzyme glutathione reductase as a source of electrons to reduce oxidized glutathione (GSSG) into reduced glutathione (GSH).
Also has a minor role in reducing MetHb to Hb
150
What does GSH do?
GSH acts with glutathione peroxidse enzyme to prevent oxidative damage to cell membranes by neutralizing oxidizing agents. Protects membrane components and cellular enzymes and hemoglobin from oxidation.
151
What does decreased activity in these glycolytic pathways cause?
Premature hemolysis due to membrane damage, enzyme damage, and failure of active transport.
152
What are the three functions of the erythrocyte?
1. Oxygen transport
2. CO2 transport
3. Nitric oxide transport
153
How is oxygen transport accomplished?
O2 molecules bind to the ferrous iron atoms in hemes of hemoglobin. Each heme binds one O2, so each hemoglobin and carry 4 oxygen molecules. Usually it only carries 3
154
How does reverse oxidation work?
Iron atoms can bind and release oxygen molecules several times without become oxidized themselves
155
What is oxygen saturation?
It refers to the amount of O2 carried by the hemoglobin in the blood and is expressed by a percentage of the total capacity to carry oxygen
156
What are normal oxygen saturation percentages?
95% in arterial blood and 70% in venous blood
157
The amount of O2 carried by hemoglobin is effected by three factors:
1. Availability of oxygen
2. Availability of enough reduced hemoglobin
3. Oxygen affinity of hemoglobin
158
What happens when oxygen affinity is high? When it is low?
High: hemoglobin easily and quickly bind with oxygen and hang on to them
Low: hemoglobin releases oxygen it is carrying and has difficulty binding with more
