Hematology Unit I Flashcards
1
Q
Define Hematopoiesis
A
“Blood making” that typically occurs in the bone marrow that results in the formation of the mature, functional red blood cells, white blood cells, platelets and miscellaneous other cell types (osteoclasts, dendritic cells, etc).
2
Q
Define Erythropoiesis
A
Is the process which produces red blood cell (erythrocytes).
3
Q
Name two important substrates to make erythrocytes?
A
Vitamin B12 and Folic acid
4
Q
Define anemia
A
insufficient red cell mass to adequately deliver oxygen to peripheral tissues
5
Q
What is erythropoietin?
A
a hormone produced by the kidney, essential for stimulating the marrow to make red blood cells.
6
Q
Define Hemolysis
A
Red cell destruction
7
Q
What is hemostasis?
A
The arrest of bleeding, which allows blood to clot in response to damage to a blood vessel.
8
Q
What are the three factors needed for hemostasis to occur?
A
platelets, endothelium, and coagulation proteins
9
Q
Define Thrombosis
A
pathologic clots that can cause ischemia, blockage of blood flow
10
Q
Explain the shape of an erythrocyte and reasoning behind the shape
A
Biconcave to increase surface area for gas exchange. Also, high surface area to volume ratio means that the RBC can be squeezed into all different kinds of shapes.
11
Q
Describe the composition of an erythrocyte
A
No nuclei or mitochondria
12
Q
What are the five types of white blood cells in the blood?
A
- lymphocytes
- neutrophils (also known as polymorphonuclear cells or PMNs)
- monocytes
- eosinophils
- basophils.
13
Q
What is Leukemia?
A
cancer cells in the bone marrow and blood
14
Q
What is lymphoma?
A
cancer cells in the lymph nodes or other lymphoid tissue, predominantly outside the bone marrow
15
Q
What is acute leukemia
A
The cells are immature in their degree of differentiation and that the clinical course is usually rapidly progressive without intervention
16
Q
What is chronic leukemia?
A
t the cells are more mature in their differentiation and that the disease follows a more indolent (causing little to no pain) clinical course.
17
Q
What is lymphoid leukemia?
A
arising from lymphocytic lineage
18
Q
What is myeloid leukemia?
A
arising from one of the other cell types in the marrow, other than lymphocytes
19
Q
What are platelets?
A
the cellular component of the blood responsible for hemostasis.
20
Q
Where do platelets come from?
A
Platelets are actually small cell fragments produced
from large, polyploid cells in the bone marrow called
megakaryocytes.
21
Q
What is the Ferrous form of iron?
A
reduced Fe2+
22
Q
What is Ferric iron
A
Fe3+
23
Q
What form of iron can bind oxygen?
A
Ferrous Fe2+
24
Q
What is methemoglobin?
A
Hemogloblin that has ferric iron (Fe3+) and cannot bind oxygen
25
What enzyme reduces ferric Fe?
cytochrome B5 reductase
26
What is deoxygenated hemoglobin called?
Taut formation
27
What is oxygenated hemoglobin called?
Relaxed (R) conformation
28
Define allostery
substrate binding at one site on a protein leads to altered confirmation at other binding sites on the protein
29
What is positive cooperativity?
If the allosteric changes lead to increased affinity for substrate at the other binding sites, it is termed positive cooperativity
30
myoglobin dissociation curve vs hemoglobin
myoglobin is a monomer so you don't get positive cooperativity. It tightly binds any oxygen at very low partial pressure of oxygen. Not a good transport protein
31
what is the p50?
partial pressure of oxygen when hemoglobin is 50% saturated
32
What does it mean to have a shift in the right direction for the hemoglobin curve?
Less oxygen affinity
33
Explain the Bohr effect..
if you have a more acidic environment, hemoglobin has less oxygen affinity and the curve will shift to the right
34
What happens to the hemoglobin curve if you raise the pH?
the curve will shift to the left. Hemoglobin has higher oxygen affinity
35
What happens to the hemoglobin curve if you increase CO2?
pH goes down, oxygen affinity goes down, curve shifts to the RIGHT
36
What happens to the hemoglobin curve if you increase temperature?
Oxygen affinity goes down and curve will shift to the right.
Tissues are working hard and need their oxygen!
37
What happens to the hemoglobin curve if you increase 2,3-BPG?
it binds in the pocket of beta chains in hemoglobin and stabilizes it in the Taut conformation. Therefore, oxygen affinity goes down and curve shifts to the RIGHT
38
What chromosome is the alpha globin gene?
chromosome 16
39
On what chromosome is the beta globin gene?
chromosome 11
40
How many alpha globin genes do you have?
4.
You have 2 on each gene and one gene from each parent
41
How many beta globin genes do you have?
2
42
What are heinz bodies?
precipitated hemoglobin in the red blood cells
43
What is Hemoglobin Koln?
A mutation of the beta chain that increases oxygen affinity and shift curve to the left.
44
What is Hemoglobin Poole?
A mutation of the gamma chain. Affects infants --> hemolytic anemia but resolves itself within a few months
45
Explain Hemoglobin Chesapeake
A mutation in the alpha globin chain that increases oxygne affinity. Kidneys don't sense as much oxygen and produces more erythropoietin to compensate causing an increase in RBC production.
Patient appears red
46
In relationship to hemoglobin, when will you see cyanosis?
When you have an increased amount of deoxygenated hemoglobin
47
What affect does the methemoglobinemia have on the curve?
It shifts the curve to the left. Although the ferric iron prevent oxygen from binding this increases the affinity for oxygen for the remaining sites that can bind oxygen and they are less likely able to RELEASE their oxygen now.
48
What is the treatment for methemoglobinemia?
methylene blue
49
What is the erythrocyte lifespan in the periphery?
120 days life span
50
What is the platelet lifespan in the periphery?
7-10 days life span
51
What is the neutrophils lifespan in the periphery?
7 hour half life
52
Up until the 3rd month of gestation, where does hematopoiesis take place?
In the yolk sac
53
From the second to the seventh months of gestation, where does hematopoiesis take place?
In the liver and to a lesser extent the spleen
54
By the time of birth, where does hematopoiesis take place?
the bone marrow should be firmly established as the site of
| hematopoiesis
55
By the time an individual is 18 to 20 years old 90% of
| hematopoietically active marrow is located..
Within the axial skeleton, in the vertebrae, pelvis, sternum, ribs and skull.
56
What is extramedullary hematopoiesis?
Hematopoiesis outside of the bone marrow after birth.
| -distinctly abnormal
57
- Thrombopoietin (TPO) promotes..
promotes megakaryopoiesis
58
Granulocyte-monocyte colony stimulating factor (GM-CSF)
promotes granulopoiesis and monopoiesis
59
Granulocyte colony stimulating factor (G-CSF)
promotes granulopoiesis (neutrophils, basophils, and eosinophils
60
Monocyte colony stimulating factor (M-CSF)
promotes monopoiesis
61
Interleukin-5 (IL-5)
promotes production of eosinophils
62
Interleukin-3 (IL-3)
promotes production of basophils
63
What is the expected size of the central pallor in a mature red blood cell?
Should be 1/3 of the diameter
64
What is the ascending order of a maturing erythrocyte?
pronormoblast → basophilic normoblast → polychromatophilic normoblast → orthochromatic normoblast → reticulocyte → erythrocyte.
65
Thrombopoiesis
thrombopoietin - helps differentiate, mature, and release platelets in periphery
66
Why do megakaryocytes appear fuzzy?
There are pseudopodia coming out and eventually releasing platelets
67
How many red blood cells are present in the average 70 kg man?
25 trillion
68
How many cell divisions in a proerythroblast?
3-5 mitotic divisions
69
How long does it take for an erythroblast to mature in the bone marrow?
2-7 days
70
How long does a reticulocyte stay in the periphery?
1-2 days
71
Normal RBC diameter?
6-8 micometers
72
What is the most common granulocyte?
Neutrophils
73
Granulopoiesis takes how many mitotic divisions?
4-5
74
How long is the mitotic pool during granulopoiesis?
3-5 days
75
How long is the maturation pool during granulopoiesis?
5-7 days
76
How long does it take for a granulocyte to mature in the bone marrow?
8-12 days
77
What growth factor is required for mast cells?
SCF
78
Where are mast cells found?
In the tissues
79
What is the main difference between monocytes, macrophages and histiocytes
monocytes found in the peripheral blood
macrophages in the tissue
histiocytes found in specific tissues
80
What is a defining characteristic of a monocyte under the microscope?
they have vacuoles
81
Which lymphocyte will be more prevalent in the bone marrow?
B-cells
82
Why are bone marrow core biopsies done at the iliac crest?
That's where most of hematopoiesis is occurring in adulthood
83
What are the main features a pathologist evaluates in a bone marrow core biopsy?
```
Marrow cellularity
myeloid:erythroid
megakaryocyte frequency
focal findings
Iron levels
Lesions
```
84
Define Cellularity
the portion of the marrow that is hematopoietically active; non-hematopoietically active marrow is occupied by stromal elements, which usually is predominantly fat.
85
How long are monocytes in the circulation?
20 days
86
What is anemia
Anemia is insufficient red cell mass to adequately deliver oxygen to peripheral tissues.
87
What are the measurements used to define the existence of anemia?
1. Hemoglobin concentration (Hgb), g/dl
2. Hematocrit (Hct), % volume of red cells in blood
3. Red blood cell count, cells x1012/L
88
How do Hg and Hct measurement vary with age?
At birth, you have a lot of Hg and Hct which then declines until you are 6-10 years of age. Then it increases once you're an adult
89
Define reticulocyte count
the number of reticulocytes per 1000 red blood cells counted and is presented as a percent. normal range is from 0.4-1.7%
90
Define absolute reticulocyte count
the percent of reticulocytes times the red count (red count approximately 50,000/microL). Anything over 50,000 is considered an increase over baseline maintenance production of red cells.
helps determine the relevance of the reticulocyte count
91
What is the reticulocyte index?
indicates whether bone marrow is producing an appropriate response to the anemia. Should be between 1 and 2.
92
What does a reticulocyte index >2 mean?
indicates loss of red blood cells (destruction, bleeding, etc) leading to increased compensatory production of reticulocytes to replace the lost red blood cells.
93
What are the symptoms of anemia?
shortness of breath, fatigue, rapid heart rate, dizziness, claudication, angina, pallor
94
What are signs of anemia?
tachycardia, tachypnea, dyspnea, pallor
95
What is the most common cause of microcytic anemia?
iron deficiency
96
Where is majority of iron stored?
In hemoglobin
97
What are the primary storage forms of iron?
Ferritin and hemosiderin
98
What's the main difference between ferritin and hemosiderin?
Hemosiderin is a storage form of iron that you can't mobilize well
99
What is the significance of protoporphyrin in iron deficient erythropoiesis?
the RBC protoporhyrin count goes up.. Protoporphyrin is the precursor to porphyrin that makes the heme ring to bind Fe
100
What are factors that increase iron absorption
1. Vitamin C - keeps it in the right valence state
2. Gastroferrin - binds Fe in stomach and delivers it to duodenum
3. Low ph - increases solubility
4. Erythropoietic activity
5. contaminated water
101
What are factors that decrease iron absorption
phytates and oxalates
| presences of protein and amino acids
102
Lab results indicative of iron deficiency?
```
↓ O2 carrying capacity (Hgb, Hct)
↓ production (reticulocyte count and index)
Microcytosis (↓ MCV, smear findings)
Hypochromia (↓ MCHC, smear findings)
Wide range in size of cell (↑ RDW)
```
103
How to treat iron overload?
Phlebotomy
| Iron chelators
104
What conditions are associated with underproduction anemia?
```
Chronic infections
Chronic non-infections
Malignant diseases
Lead intoxication
Renal insufficiency
Endocrine Disorders
```
105
What are the clinical findings associated with anemia due to chronic inflammation, infection, or malignancy?
Fever (duh), althralgias, arthritis, poor appetite
| local pain, coughing, or swelling
106
What are the clinical findings associated with anemia due to lead intoxication?
Personality changes, irritability, headache, weakness, weight loss, abdominal pain, and vomitting
107
What are the clinical findings associated with anemia due to renal insufficiency?
fatigue, pallor, decreased exercise tolerance, dypsnea, tachypnea
108
What are the clinical findings associated with anemia due to Endocrine?
weight gain or loss, skin, nail, hair changes. Nausea, vomiting, dehydration, weakness and circulatory collapse associated with adrenal insufficiency
109
What cause anemia related to malignancy, infection and inflammation? (pathophysiology)
neoplasim/sepsis causes an increase in INFbeta and TNF which leads to decrease in iron, erythropoietin and reduction in RBC count.
Chronic infection and inflammation causes an increase in IL-1 and INFgamma which also leads to decrease in iron, EPO, and RBC production.
110
What is the pathophysiology of lead intoxication anemia?
Lead inhibits the synthesis of protoporphyrin and iron. It inhibits the enzyme that inserts iron into protoporphyrin and therefore Heme production and hemoglobin decrease.
111
What is the pathophysiology of renal insufficiency anemia?
No EPO is being produced and leads to decrease in RBC production
112
What are significant laboratory findings associated with anemia due to malignancy, inflammation, and infection?
The iron serum levels are low BUT the total iron binding capacity (TIBC) remains normal or low.
Iron storage is not affected and ferratin levels remain either normal or slightly increased
decreased EPO but not completely diminished
113
What are significant laboratory findings associated with anemia due to lead intoxication?
```
Increase in protoporphyrin
Microcytosis
mild hypochromia
Basophilic stippling
increased lead levels
```
114
What are significant laboratory findings associated with anemia due to renal insufficiency?
Not seen until renal function severe anemia
normochromic/ normocytic
**EPO deficiency
115
What are significant laboratory findings associated with anemia due to hypothyroidism?
mild anemia, usually normochromic and normocytic but can be micro or macrocytic
116
What are significant laboratory findings associated with anemia due to hyperthyroidism?
usually normocytic but can be microcytic as well
117
What are significant laboratory findings associated with anemia due to adrenal glands?
mild anemia, normocytic
118
When should you transfuse red blood cells?
Only transfuse red cells when the severity of anemia has potential for cardiovascular decompensation.
119
What are the risks associated with excessive EPO?
Risk of stroke so need to be sure when to administer
120
When should you administer EPO to treat anemia?
EPO is used in specific conditions where there is an absolute deficiency or where EPO levels are decreased out of proportion to the degree of anemia and administration is
known to induce a response.
121
What are sideroblasts?
atypical, abnormal nucleated erythroblasts (precursors to mature red blood cells) with granules of iron accumulated in the mitochondria surrounding the nucleus
122
What are the laboratory and clinical findings of sideroblastic anemia?
```
variable anemia
hypochromic
microcytosis
rig sideroblasts
accumulation of iron in mitochondria
```
123
What happens when you are deficient in vitamin B12 and folic acid?
Deficiencies of folic acid and vitamin B12 profoundly affect the maturation process of red cell precursors in
the marrow. The cells increase in size, arrest in S phase of mitosis, and then undergo destruction, resulting in ineffective erythropoiesis and anemia
124
These lab findings are consistent with what disorder?
An increase in cell size, cells arrested in S phase of mitosis, which then undergo destruction, resulting in ineffective erythropoiesis and anemia
Vitamin B12 and folic acid deficiency
125
What foods contain Vitamin B12
meat, eggs, and milk
| not as common in vegetables
126
What is pernicious anemia
vitamin B12 deficiency due to autoimmune destruction
| of IF-producing gastric parietal cells.
127
What foods contain folic acid?
widespread in food
| cereal, bread, fruits, vegetables, meats and fish
128
what is the most common cause of vitamin B12 deficiency?
autoimmune disease - pernicious anemia
129
what is the most common cause of folic acid deficiency?
inadequate dietary intake
130
Is folic acid or vitamin b12 deficiency more rapid in onset?
folate deficiency is more rapid (within weeks), particularly in the setting of malabsorption or alcoholism.
In someone who is well-nourished, Vitamin B12 deficiency takes several months to develop because of its long half-life within the body and large hepatic stores.
Vitamin B12 deficiency develops more slowly and is more likely associated with malabsorption.
131
What hematologic changes are observed in vitamin B12 and folic acid deficiency?
Bone marrow:
Megaloblastic changes seen both in red cell and white cell precursors: at any stage, large, more immature nuclei.
Cytoplasmic maturation is normal
Intramedullary destruction (in the bone marrow)
Erythroid hyperplasia.
Peripheral blood:
Macrocytosis (MCV > 97 fl in adults)
Ovalocytes
Hypersegmented nuclei in neutrophils
As anemia progresses, poikilocytes and fragmentation.
In severe cases, see neutropenia and thrombocytopenia.
↑ bilirubin (and other evidence of hemolysis, destruction in marrow)
Retic index
132
Neurologic Features of Vitamin B12 Deficiency
Sensory losses first: numbness, tingling, loss of fine sensation.
Also loss of proprioception.
Ataxia, spasticity, gait disturbances, positive Babinski
reflex.
Cerebral symptoms: cognitive and emotional changes.
Anemia may be absent in 28% of cases with neurologic problems.
Neurologic defects may be non-reversible.
133
What labs can you run to distinguish vitamin B12 deficiency from folic acid deficiency?
methylmalonic acid levels increase in vitamin B12 deficiency and not folic acid deficiency
134
What is a sensitive marker for deficiency of B12 and folate acid in the tissue?
Measurement of plasma homocysteine levels
| has been used as a more sensitive marker of deficiency of B12 and folate in the tissues.
135
What is the risk of misdiagnosing a patient with folic deficiency?
If the patient actually suffers from vitamin B12 deficiency, Extra folate can make the neurological affects of vitamin B12 more severe
136
How does the schilling test work?
1 μg of radiolabeled cobalamin (vitamin B12) is given orally to a fasting individual. 2 hours later give them more vitamin B12, if radiolabeled cabalamin ends up in the urine you know the patient is absorbing vitamin B12.
137
What is thalassemia?
Thalassemia is a condition in which there is underproduction of a hemoglobin chain due to a variety of mutations that result in poor or absent function of the globin gene
138
Alpha thalassemia is frequent in what populations?
South east asian, african, and Mediterranean
139
Which population is most likely to have a hydrops fetalis during pregnancy?
Southeast asians commonly have second trait thalassemia in the form of --/aa (cis) which can lead to --/--
Africans typically have -a/-a (trans) and child can survive
140
What is hemoglobin H disease?
--/-a
141
What is the most common mutation causing beta thalassemia?
Point mutation
142
When is fetal hemoglobin present?
2nd trimester - 6 months of life (after birth)
| a2gamma2
143
type of genetic mutation in alpha thalassemia?
gene deletion
144
What is thalassemia minor?
mild anemia, asymptomatic trait state
145
What is thalassemia intermedia?
moderate anemia, intermittent transfusions
146
What is thalassemia major?
severe anemia, transfusion-dependent
147
What is bilirubin?
Bilirubin is the yellow breakdown product of normal heme catabolism, caused by the body's clearance of aged red blood cells which contain hemoglobin
148
How do you diagnose thalassemias?
CBC and hemoglobin electrophoresis
149
What can lead to a false negative B thalassemia diagnosis?
iron deficiency will cause the production of Hb2 to decrease and make the levels appear "normal" when in reality they should be increased. B-thalassemia can then be missed.
150
What is protective of the polymerization of sickle RBC?
fetal hemoglobin
151
What are potential adverse effects with sickle cell trait?
Microscopic hematuria (blood in the urine)
Renal papillary necrosis (gross hematuria)
Isosthenuria (mild urinary concentrating defect)
Increased risk of chronic kidney disease
Increased risk of blood clots
Splenic infarction (altitude or depressurized flight)
Exertional heat illness/rhabdomyolysis/death (sports-related)
152
What is the relationship between hypoxic and high altitude conditions to sickle cell anemia?
Under these conditions, the RBC is more likely to sickle and blood vessels can become acutely damaged and constricted, which may promote significant, sudden
vaso-occlusion
153
What are some acute complication of sickle cell disease?
Acute chest syndrome
Infections: streptococcus, hemophilus influenza due to splenic infarction
Aplastic crisis: parovirus B19
154
Treatment for sickle cell?
Hydroxyurea and transfusions
155
What is the normal hemoglobin level for males and females?
Males: 13.5 g/dL
| FemalesL 12.4 g/dL
156
What type of anemia leads to extramedullary hematopoiesis?
Beta thalassemia major
157
Parovirus B19
shuts down the production of RBCs temporarily. Does not severely affect normal individuals. However, if you have thalassemia you cannot afford to lose anymore RBCs!
158
The existence of G-6-PD deficiency may be associated with a selective resistance to
Plasmodium vivax
159
Name the warm antibody that can lead to hemolytic anemia?
IgG
160
What are important vaccinations for a splenectomy?
influenzae b, S. pneumoniae, and meningococcal (before splenectomy).
161
What is the equation for bone marrow cellularity?
100-age
