Heme Unit 2 Flashcards
(201 cards)
1
Q
What is Colony Stimulating Factors?
A
Cytokines that are produced by the stromal cells to stimulate the development of blood cells.
2
Q
What is cell commitment?
A
Hematopoietic precursor cell genetically commits to differentiate into a certain cell type.
3
Q
What is maturation?
A
The actual stages of development. **Expression of commitment and differentiation.
4
Q
Types of hematopoietic stem cells
A
Pluripotent
Multipotent
5
Q
What is differentiation?
A
The process of generating several different cell lines.
**Allow expression of certain genes while restricting others.
6
Q
Where does hematopoiesis occur in the bone marrow?
A
Medulla
7
Q
Functions of the spleen include:
A
*Culling
*Pitting
*Reservoir for platelets and RBCs
(2nd lymphoid organ)
8
Q
Where does antigen dependent lymphopoiesis occur?
A
*Spleen
*Lymph nodes
(actually perform their roles)
9
Q
Where does antigen independent lymphopoiesis occur?
A
*Bone marrow
*Thymus
(learn to function)
10
Q
Bones that remain hematopoietically active?
A
End of long bones
Pelvis, iliac crest
Skull
Sternum
Scapula
Vertebrae
Clavicles
11
Q
What is the role of fibroblasts in hematopoietic microenvirnment?
A
They produce a support network of collagen for developing cells.
(extracellular matrix)
12
Q
What is the role of adipocytes in hematopoietic microenvironment?
A
They produce fatty yellow bone marrow.
13
Q
What is the role of macrophaphes in hematopoietic microenvironment?
A
They produce cytokines to stimulate cell development
14
Q
What are the 3 main stromal cells?
A
- Macrophage
- Adipocytes
- Fibroblasts
15
Q
What are the secondary lymphoid tissues?
A
Spleen
Lymph nodes
16
Q
What are the primary lymphoid tissues?
A
Bone Marrow
Thymus
17
Q
In utero, when does hematopoiesis shift to the bone marrow?
A
6 month gestation
18
Q
When does the liver become the chief hematopoietic ogran for the embryo?
A
3 month gestation
19
Q
How many days gestation does hematopoiesis begin?
A
18 days
20
Q
How many RBCs do we produce each day?
A
2 x 10^11
21
Q
What is tissue homeostasis?
A
The balance maintained between cellular proliferation, differentiation, and apoptosis.
22
Q
Multipotent Hematopoietic Stem cells can go which 2 paths?
A
Differentiate into myeloid or lymphoid stem cells OR
Self-renew
23
Q
What cells are highly mitotic cells?
A
Progenitor cells
24
Q
Progenitor cells are also called?
A
CFU: colony forming units
BFU: burst forming units
25
Progenitor cells lose what capibility?
Self renewal
26
What do progenitor cells become with each division?
progressively committed
27
What do Precursor cells lose the capability to do?
Divide
**except lymphocytes
28
What are Erythroblasts also known as?
Nucleated RBCs
Normoblasts
29
Reticulocytes are also known as?
Polychromatophilic RBCs
30
What is the sequence of the RBC maturation?
1. Rubriblast
2. Prorubricyte
3. Rubricyte
4. Metarubricyte
5. Reticulocytes
6. Erythrocyte
31
How long do Normoblasts (nucleated RBCs) take to mature in the bone marrow?
5-7 days
32
How long do Reticulocytes mature in the bone marrow?
2-3 days
33
Hypoxia stimulates the production of what by specialized kidney cells?
Erythropoietin (EPO)
34
Difference between EPO and CSF?
CSF are produced by stromal cells and are responsible for the proliferation of precursor cells.
EPO only stimulates development of RBC precursors
35
Hormones other than EPO that can have an effect on hematopoiesis
Adrenal cortical hormones: Androgens, Aldosterone, and Cortisol
Thyroid hormone
Growth hormone
36
What is the earliest recognizable RBC precursor?
Rubriblast
37
What is Rubriblast also known as?
Pronormoblast
38
What is Prorubricyte also known as?
Basophilic Normoblast
39
What is the cracked appearance of the nucleus in Prorubricyte and Rubricyte called?
Parachromatin clearing
40
What is the last stage capable of undergoing mitosis in RBC maturation?
Rubricyte
41
What is Metarubricyte also known as?
Orthochromic Normoblast
42
What is the last stage of RBC maturation with a nucleus?
Metarubricyte
43
The last 20% of Hgb is made in what stage of RBC maturation?
Reticulocyte
44
Normal % of reticulocytes in peripheral blood?
0.5-2.5% of all circulating RBCs
45
What stain is needed to ID Reticulocytes?
Supravital Stain
46
If using Wright Stain what are reticulocytes called?
Polychromatophilic erythrocytes
47
What is the purpose of Supravital stain?
Makes the residual RNA visible
(New Methylene Blue used)
48
What are the functions of the Erythrocyte membrane?
Oxygen transport
Durability/strength
Balance ion and water concentration
Flexibility to fit through small vessels
49
What is responsible for the Zeta Potential of RBCs
Integral Proteins in the erythrocyte membrane
50
What do the peripheral proteins in RBCs do?
Form the cytoskeleton
Provide flexible, fluid structure
51
How do RBCs produce ATP?
Anaerobic glycolysis
52
What is the purpose of Pyruvate Kinase in RBC ATP production?
Turns sugar into ATP
53
A deficiency in Pyruvate Kinase can cause?
hypoglycemic erythrocytes
54
What is the purpose of glutathione in RBC metabolism?
Becomes oxidized instead of Hgb
55
What does the Hexose Monophosphate Shunt do?
Protects hgb from being chemically oxidized
56
Rubriblast
57
Prorubricyte
58
Rubricyte
59
Metarubricyte
60
Reticulocyte
61
If using a wright stain, what is a reticulocyte called?
Polychromatophilic erythrocyte
62
Glutathione is oxidized instead of Hgb in what pathway?
Hexose Monophosphate Shunt
63
Important enzyme in HMP
G6PD
Glucose-6-phosphate dehydrogenase
64
What pathway returns methemoglobin to a reduced state?
Methemoglobin reductase pathway
65
What does the methemoglobin reductase pathway ensure?
That Hgb can bind and transport oxygen
66
What does a methemoglobin reductase deficiency cause?
Decreased oxygen carrying
hypoxia results in cyanosis
67
What forms 2,3 BPG
Rapoport-Leubering Shunt
68
What does the Rapoport-Leubering Shunt regulate?
Oxygen affinity by releasing the oxygen off heme
69
An important enzyme in Rapoport-Leubering Shunt
BPG-Synthetase
70
What is the porphyrin ring in heme called?
protporphyrin IX
71
What is deoxygemoglobin
Iron ions in the ferrous state
72
What is oxyhemoglobin
Iron ions in the ferric state
73
The predominant form of Hgb in adults
Hemoglobin A
2 alpha
2 beta
74
Predominent form of Hbg in the fetus and newborns
Hemoglobin f
2 alpha
2 gamma
75
How is Hgb F different from Hgb A?
the gamma chain is a beta chain with a SERINE in place of Histidine at the 143rd position
76
What does the serine interference in the gamma chain do?
Interferes with 2,3 BPG allowing Hgb F to have a higher affinity for Oxygen
77
Normal adult Hbg composition
>95% Hbg A
1-4% Hbg A2
<2% Hgb F
78
What Hgb is associated with Sickle Cell Anemia
Hgb S
79
What Hgb state can't bind to oxygen?
Methemoglobin
Fe in ferric state
80
What is carboxyhemoglobin
Hbg has a higher affinity for CO than oxygen
81
What are culled RBC degraded by?
macrophages
82
After iron is extracted from heme, what does it further break down to?
unconjugated bilirubin
83
What binds to Hgb to render it non toxic?
Haptoglobin
84
What is the definition of anemia?
A decrease in oxygen carrying capacity of blood
85
What is elevated in Anemia that increases oxygen utilization?
2,3 BPG
86
MCV at birth
108fL
macrocytic
87
MCV 6 months-2 years
77fL
microcytic
88
MCV 18+ years
90fL
normocytic
89
What is indicated by an elevated RDW?
Anisocytosis
90
Anisocytosis
-variation in RBC size
91
Polychromatic RBC
92
What are acanthocytes also known as?
Spur or thorn cells
93
Clinical Conditions of acanthocytes
Liver disease
Lipid metabolism disorders
fat malabsorption
increased membrane cholesterol
94
acanthocytes
95
What are schistocytes also known as?
Fragmented RBCs
"crap cells"
96
Clinical conditions of Schistocytes
Microangiopathic hemolytic anemia (MAHA)
Uremia
HDN
DIC
97
What is a subcategory of Schistocytes?
Keratocytes
aka Helmet cells
98
What are drepanocytes also known as?
Sickle Cells
99
Clinical conditions of Drepanocytes
Sickle cell anemia
Hgb SC disease
100
Drepanocyte
101
Clinical conditions of Spherocytes
Hereditary spherocytosis
PK deficiency
Severe burns
Immune mediated hemolysis
102
Spherocyte
103
What are dacrocytes also known as?
Teardrop cells
104
Clinical conditions of dacrocytes
Sign of extramedullary hematopoesis
Myelophthisic anemia
105
Dacrocyte
106
What are Echinocytes also known as?
Burr cells
Crenated cells
107
Clinical conditions for echinocytes
Uremia
liver disease
stomach cancer
108
Echinocyte
109
What are ovalocytes also know as?
elliptocytes
110
Clinical conditions of ovalocytes
Hereditary ovalocytosis
Misc anemia
-Thalassemia
-iron deficiency
-sickle cell anemia
111
Ovalocyte
112
What are stomatocyte also known as?
Mouth cells
113
Clinical conditions of stomatocytes
Abnormal membrane ion exchange
Hereditary stomatocytosis
Liver disease
Lead poisoning
114
Stomatocyte
115
What are codocytes also known as?
Target cells
116
Clinical conditions for codocytes
Thalassemia
Liver disease
Misc anemias
117
codocyte
118
Clinical conditions that cause Basophilic Stippling
Lead poisoning
Thalassemia
Sideroblastic anemia
Misc anemias
119
Basophilic Stippling
120
What is Basophilic Stippling composed of?
Aggregated rRNA
121
Clinical conditions that cause Howell-Jolly Bodies
Post-splenectomy
Hemolytic anemia
Megaloblastic anemia
122
What are Howell-Jolly Bodies composed of?
Residual nuclear DNA
123
Howell-Jolly Bodies
124
Clinical conditions that cause Pappenheimer Bodies
Post-splenectomy
Sideroblastic anemia
Megaloblastic anemia
Hemoglobinopathies
125
Pappenheimer bodies are composed of?
Aggregated Fe
126
Pappenheimer Bodies
127
Clinical conditions that cause Heinz Bodies
G6PD deficiency
Hemoglobinopathies
128
Heinze Bodies are composed of?
Precipitated Hgb
129
Heinz bodies
130
What are the 4 types of Microcytic Anemia?
1. Sideroblastic
2. Iron deficiency
3. Anemia of Chronic Disease
4. Thalassemia
131
Microcytic anemias that have abnormal iron metabolism?
Sideroblastic
Iron deficiency
Anemia of Chronic disease
132
Microcytic anemia that has abnormal globin production?
Thalassemia
133
Lab results for Iron Deficiency Anemia
Decreased Ferritin
Increased Transferrin
Increased TIBC
Decreased serum iron
Elevated RDW
134
What is Pica
Craving Non food
135
Causes of Sideroblastic Anemia
Hereditary: enzyme deficiency
Toxins
Myelodysplastic syndrome
136
What anemia has partial/abnormal heme synthesis?
Sideroblastic
137
Sideroblastic Anemia
138
What can help us differentiate between Iron deficiency anemia and Thalassemia?
RDW
RDW is elevated in Iron Deficiency
RDW is normal in Thalassemia
139
What anemia is from ineffective erythropoiesis due to poor globin synthesis?
Thalassemia
140
What anemia causes BM hyperplasia?
Thalassemia
141
What does BM hyperplasia cause?
Bone deformitites
142
What happens bc of Thalassemia's abnormal RBCs?
Excessive extravascular hemolysis
-Jaundice
Leads to gallstones
Spleen Overload
143
What happens from transfusion dependency?
Development of hemochromatosis
144
What is hemochromatosis?
Iron overload which leads to iron toxicity
145
Inclusions that are seen in Thalassemia?
Howell Jolly Bodies
Basophilic stippling
146
Alpha Thalassemia affects?
The quantity of production of alpha globin chains
147
What Thalassemia is asymptomatic?
(-a/aa)
Single deletion
148
What Thalassemia causes mild anemia?
(--/aa)
Double deletion
149
What Thalassemia causes Hgb H disease?
(--/-a)
Triple deletion
150
What Thalassemia causes development of hydrops fetalis?
(--/--)
Quadruple deletion
151
What Thalassemia is from a genetic mutation?
Beta Thalassemia
152
What is Beta + Thalassemia
A partial block in Beta chain synthesis
153
What is Beta 0 Thalassemia
A complete absence of Beta Chain synthesis
154
What does the reduction of Beta chain synthesis affect?
Production of Hgb A
155
What are the 3 stages of Iron Deficiency Anemia development?
1. Iron depletion
2. Iron deficient erythropoiesis
3. Iron deficiency anemia
156
The 3 types of Megaloblastic anemia?
1. B12 deficiency
2. Folate deficiency
3. Hematologic neoplasms
157
Non-megaloblastic anemia is from?
Chronic liver disease
158
What is a megaloblast?
A large, abnormal nRBC
159
Inclusions seen in Megaloblastic anemia
Pappenheimer bodies
Howell Jolly Bodies
160
What is seen in only megaloblastic anemia patients?
Hypersegmented neutrophils
161
Folate deficiency can cause?
Decreased hematopoiesis
Increased apoptosis
Megaloblastic maturation
Birth defects
162
Neurological problems from B12 deficiency
Psychotic symptoms
Motor and sensory abnormalities
Defective Fatty Acid degradation (affects myelin sheath)
163
What is Intrinsic factor deficiency known as
Pernicious anemia
164
What produces intrinsic factor
Gastric parietal cells
165
what is intrinsic factor necessary for?
Absorption of B12
166
Types of Normocytic Anemia
Hypoproliferative anemia
Hemolytic anemia
167
What can cause Hypoproliferative anemia
Bone marrow disorders
Chronic renal disease
168
What are the types of Hypoproliferative anemias
Aplastic
Myelophthisic
169
Aplastic anemia is caused by?
bone marrow failure
170
What lab finding is seen in aplastic anemia
Pancytopenia
171
Myelophthisis is caused by
Bone marrow being infiltrated by malignant cells
172
What are the membrane abnormalities seen in hemolytic anemia?
1. Hereditary spherocytosis
2. Hereditary acanthocystosis
3. Hereditary stomatocytosis
4. Hereditary ovalocytosis
5. Hereditary pyropoikilocytosis
6. Paroxysmal nocturnal hemoglobinuria (PNH)
173
How does hereditary spherocytosis cause anemia?
From excessive extravascular hemolysis
174
What hemolytic anemia is caused by liver disease and the lipid problems from that?
Hereditary acanthocytosis
175
Hereditary stomatocytosis is from what abnormality?
Membrane ion exchange
176
Abnormal structural proteins causes what hemolytic anemia?
Hereditary ovalocytosis
177
What hemolytic anemia is sensitive to heat
Hereditary pyropoikilocytosis
178
Complications of PNH
Development of Fe or folate deficiency anemia
Thrombosis
Renal disease
179
What membrane abnormality is aqcuired
PNH
180
What hemolytic anemia occurs mostly at night?
PNH
181
What two enzyme deficiencies result in hemolysis
G6PD
Pyruvate kinase
182
What happens in G6PD deficiency
Oxidized heme accumulates
Poor Oxygen carrying capability
Heinz bodies cause membrane damage
183
What is kernicterus
Brain damage from extreme buildup of bilirubin in the brain
184
What enzyme deficiency can cause kernicterus
G6PD
185
What enzyme deficiency causes decreased haptoglobin
G6PD
186
Pyruvate deficiency causes what
Ion pumps being impaired
Cellular dehydration
Increased 2,3 BPG production
187
An increased 2,3 BPG does what to Oxygen
increases the dissociation from Hgb
188
Qualitative hemoglobinopathy causes?
Sickle cell anemia
189
What is substituted on the Beta chain in Sickle Cell Anemia
Valine instead of glutamic acid at the 6th position
190
Sickle cell occurs because?
Deoxygenated hgb S allows polymerization of surrounding hgb S molecules
191
What anemia can cause bone pain (cortical thinning)?
Sickle cell
192
What is vaso-occlusive crisis
Sickle cells block blood flow and the tissues lack oxygen
193
What is substituted in Hgb C Disease?
Lysine for glutamic acid in the 6th position
194
Hgb C crystal
195
Types of Extrinsic Hemolytic Anemia
Antibody Mediated
Malaria
Chemical/Physical
Mechanical
196
Malaria is caused by?
Plasmodium falciparum
197
Malaria in the ring form
198
What is MAHA
Microangiopathic hemolytic anemia
Caused by destruction of RBC in small blood vessels when forced through fibrin strands
199
What is HUS
Hemolytic uremic syndrome
-bacterial toxins injure glomerular endothelial cells
200
What are the mechanical anemias
Maha
Hus
DIC
201
What is DIC
simultaneously clotting and hemorrhaging
