Week 1 Flashcards
1
Q
Normal morphological maturation of granulocyte precursors
A
Blast (3-4%)–> promyelocyte (2-8%) –> myelocyte (10-13%) –> metamyelocyte (10-15%)–>bands and neutrophils (25-40%)
2
Q
Which cells of granulocyte maturation form a mitotic pool in the marrow? Of those which is most common?
A
blast, promyelocyte, myelocyte (most common)
3
Q
Which cell of granulocyte maturation has primary granules?
A
promyelocyte
4
Q
Which cell of granulocyte maturation has secondary granules?
A
myelocyte
5
Q
Which cell of granulocyte maturation has a bean shaped nucleus?
A
metamyelocyte
6
Q
Which cell of granulocyte maturation has prominent hof?
A
myelocyte
7
Q
What releases G-CSF?
A
bone marrow and stromal cells
8
Q
% of bone marrow doing erythropoiesis
A
20-30%
9
Q
% of bone marrow doing myelopoiesis
A
60-70%
10
Q
What key growth factors can be mimicked by drugs and what do they stimulate?
A
EPO: BFUe–> CFUe
TPO: BFUemeg–> CFU meg
GM-CSF
G-CSF: CFUgm–> CFUg
11
Q
Where does G-CSF act?
A
Blast–> promyelocyte–> myelocyte
12
Q
What organ releases TPO and is it constiuitive or only when stimulated?
A
liver; constant
13
Q
Describe the genetic material of megakaryocytes
A
polyploid: 16-32n
14
Q
How are platelets formed?
A
proplatelets are extended into fenestrated blood vessels in bone marrow and get looped off
15
Q
What 2 things does TPO bind?
A
platelets and megakaryocytes
16
Q
In normal conditions, describe the function of TPO
A
binds mostly platelets, some goes to megakaryoctes (where it stimulates production of more megakaryocytes and platelet production).
17
Q
In low platelet, describe the function of TPO?
A
more TPO binds megakaryocytes stimulating more thrombopoiesis
18
Q
What is the cell lineage in normal maturation of erythropoiesis?
A
blast–> pronormoblast–> basophilic erythroblast–> polychomatophilic erythroblast–> normochromic erythroblast
19
Q
How much of the bone marrow is cellular and active?
A
100%-age.
20
Q
Heme synthesis requires:
A
Iron***, B6, succinyl CoA, glycine (B12+ folate(
21
Q
globin synthesis requires:
A
normal globin genes, alpha, beta, amino acids
22
Q
What usually causes globin problems in the US?
A
genetic problems rather than malnutrition
23
Q
DNA synthesis requires:
A
deoxynucleoside triphosphates (ribonucleotide reductase, thymidine (B12, folate))
24
Q
For which of the requirements for erythropoiesis is folate and B12 required?
A
DNA synthesis, Heme synthesis
25
Morphology of iron deficiency
microcytosis, hypochromia, anisocytosis (size distribution), poikilocytosis ( cell shape variation)
26
Dietary iron is in _____ state.
Oxidized: Fe3+, ferric
27
What has to happen for dietary iron to be absorbed?
It has to be reduced in the stomach to ferrous iron (Fe2+) before it can be taken up in the bowel.
28
What 2 factors affect the ability of dietary ferric iron to be reduced?
low pH, Vitamin C
29
What happens after iron is absorbed in the bowel?
It is oxidized to Fe3+ (ferric) by serum oxidases then bound to transferrin
30
Reduced transferrin levels can cause _____.
Low serum iron
31
What takes up transferrin-bound iron?
bone marrow macrophages via TfR1
32
How is TIBC calculated?
lab saturates transferrin with added iron.
33
What does TIBC tell you?
if serum iron is low due to reduced transferrin or not
34
What is % transferrin saturated?
serum iron concentration/ TIBC
35
What increases in iron deficiency?
serum transferrin and soluble transferrin receptors
36
What is reduced in iron deficiency?
serum iron, iron saturation, serum ferritin
37
Outside of red cells and transferrin, most of the body's iron stores are bound to a protein called _____.
Ferritin
38
What morphology is seen with B thalassemia?
microcytosis (may be smaller than in iron def), hypochromia, target cells,
39
Target cells are not specific; they are commonly associated with ______.
liver disease
40
How can you tell if a pt has iron deficiency or thalassemia?
Number of red cells. In iron deficiency, the number goes down. In thalassemias, its normal or increased.
41
How can you confirm a thalassemia after seeing the right lab values?
Because Hb A2 is increased and it migrates differently during electrophoresis. Hb F may also be detected if the thalassemia is severe
42
Describe the beta globin locus.
It is on chromosome 11. There are 6 copies on each chromosome. 3 are expressed in utero (epsilon, g-gamma, a gamma), psi-beta does nothing, delta is in fetus and low amounts in adults, and finally beta is the form expressed in adults
43
If expression of beta globin allele is impaired, what may increase?
Hb A2, Hb F if severe
44
Decribe the alpha globin locus
Chromosome 16; 4 copies on each chromosome. zeta 1 and 2 are expressed in utero, alpha 1 and alpha 2 in adults
45
What happens when there is a mutation in one of the 4 alpha genes (2 on each chromosome)?
Alpha thalassemia 1 trait
46
What happens if there are 2 defective alpha alleles?
alpha thalassemia 2 trait
47
What RBC problems is expected with alpha thalassemia 2 trait
mild microcytic anemia, excess Hgb Barts (gamma 4 tetramer) at birth, normal electrophoresis as adult
48
how is alpha thalassemia 2 trait diagnosed?
PCR
49
What percent of population have alpha thalassemia 2 trait
3% of blacks
50
What happens if there are 3 defective alpha alleles?
Hgb H disease (beta 4)
51
What are the clinical findings associated with Hgb H disease?
variable degree of microcytic anemia,
52
What happens if all 4 alpha alleles are defective?
lethal in utero or soon after birth, Hgb H disease
53
UTP has to be methylated to TTP. Methylation requires what?
B12 and folate
54
What happens if DNA synthesis is impaired?
fewer cells produced, normal/enhanced maturaion of cytoplasm, impaired nuclear maturation
55
What are the causes of megaloblastic anemia?
Impaired B12 uptake (pernicious anemia); impaired folate uptake (malabsorption, malnutrition), drug effect (nucleoside analogs [HAART], ribonucleotide reductase inhibitors [hydroxyurea]), intrinsic bone marrow dysfunction (myelodysplastic function)
56
_____ can impair iron storage usage.
Hepcidin
57
Chronic inflammation conditions can induce ____ production that impairs utilization of bone marrow iron stores.
Hepcidin
58
What cytokine is produced in chronic inflamattion that causes production of hepcidin?
IL-6
59
Failure to use iron stores is seen in ______.
anemia of chronic inflammation
60
How do you confirm anemia of chronic inflammation?
bone marrow biopsy
61
Describe the clinical findings of anemia of chronic disease
normocytic anemia, increased ferritin, reduced or normal serum ion, increased bone marrow iron stores.
62
Define ferritin
stores iron; has apoferritin shell and hydroxide core. It is water soluble and easy to mobilize in deficiency
63
How is hemosiderin different from ferritin?
lacks apoferritin shell
64
Define labile iron pool. How many mg of iron?
iron leaving the plasma and entering the interstitial and intracellular fluid compartments. 80-90 mg
65
What makes up the smallest pool of iron?
Transferrin- 3mg
66
How many times a day does transferrin turn over?
10
67
Where is transferrin found and how much of it is saturated?
plasma; 1/3
68
How many mg of iron do youg/ pregnant women absorb?
2/3 mg
69
How many mg of iron do men absorb?
1 mg
70
____ allows export of iron from duodenal enterocyte into circulation.
ferreportin
71
What does hepcidin do to ferreportin?
degrades it
72
What does ferriportin regulate?
transfer of iron from mom to baby; iron absorption in intestines; iron export from macrophages
73
Hepcidin is a _____ regulator of iron uptake.
negative
74
_____ inhibites hepatocytes that store iron.
Hepcidin
75
What increases the absorption of non-heme iron?
low ph, ascorbic acid; Vitamin C
76
What decreases the absorption of non-heme iron?
insoluble complexes, chelating agents
77
What 3 major things can cause malabsorption of iron?
GI tract surgery, non-tropical sprue, picca
78
What is non-tropical sprue?
gluten induced damage to differentiated villus epithelial cells of the small intestines; stop all grains except rice and corn
79
What is tropical sprue?
overgrowth of coliforms in jejunum that results in malabsorption of folic acid, cobalamin, fat, folic acid
80
causes of GI bleeding in US adults
peptic ulcer disease, hiatal hernia, chronic gastritis, hemorrhoids, intermitant bleeding after surgery, neoplasms
81
Causes of GI bleeding in infants
milk allergy (boil milk), Meckel's diverticulum
82
Most common cause of GI bleeding in underdeveloped countries
hook worm
83
Symptoms of iron deficiency
fatigue, headaches, irritability, decreased exercise tolerance, burning tongue, picca
84
physical findings in iron deficiency
pallor, glossitis, stomatitis, angular chelitis
85
What is koilonychia
spoon shaped nails associated with iron deficiency
86
How is iron deficiency treated orally?
Ferrous sulfate
87
What are the indications for parenteral iron therapy?
malabsorption, intolerance, uncooperativeness, inability of pt
88
What are some side affects associated with intravenous iron therapy?
thrombophlebitis, arthralgia, hypotension, bradycardia, nausea and vomiting, anaphylactic reactions
89
What does unbound iron due to iron overload do?
release hydroxyl radical, lipid peroxidation, fibrosis, carcinogenesis
90
____ occurs in 30% or chronic alcoholics
iron overload
91
How does alcohol lead to iron overload?
high iron content in red wines, folate def increases iron absorption
92
Clinical findings of iron overload due to alcohol
skin pigmentation, hypogonadism, glucose intolerance,
93
How is thalassemia related to iron overload?
need of transfusion can cause iron overload
94
What are the clinical findings of iron overload due to treatment of thalassemia?
1st decade: hepatomegally; lack of sexual development. 2nd decade: cardiomegally
95
What is the treatment of iron overload due to transfusions?
dextroferramine
96
____ is a group of diseases in which there is excessive absorption of iron from the gastrointestinal tract leading to iron overload of the parenchymal cells of the liver, endocrine organs, and in the heart.
hereditary hemochromatosis
97
Mode of inheritance of hereditary hemochromatosis
autosomal recessive with variable penetrance
98
What happens to hepcidin levels in hemachromatosis?
a mutation in the HFE gene occurs that results in low hepcidin levels. Iron can accumulate for years and the hepcidin levels remain low
99
Clinical symptoms of hemachromatosis
liver function abnormalities, weakness and lethargy, skin hyperpigmentation, diabetes, arthralgias, impotence, heptomas
100
Lab findings with hemachromatosis
high serum iron, low binding capacity, high saturation, high ferritin, increased iron in liver biopsy
101
Treatment for Hemachromatosis
phlebotomy
102
Why are patients with hereditary hemochromatosis told to avoid vitamin C?
It increases absorption of iron
103
How is hemachromatosis diagnosed?
HFE gene mutation analysis
104
What is the common, Type 1 hemochromatosis mutation in the HFE gene?
C282Y
105
What are the main foods containing folate?
liver, greens, yeast
106
What are the body stores of folate?
10-12 mg, 4 months worth
107
When is there an increased demand for folic acid?
pregnancy, RBC turnover in hemolytic diseases, dermatitis, certain drugs
108
What causes impaired absorption of folic acid?
tropical sprue, regional enteritis, resection of small intestines
109
Who is at risk for inadequate dietary intake of folate?
elderly, poor, alcoholics
110
Clinical features of megaloblastic anemias
insidious onset, mild jaundice, glossitis, angular stomatitis, weight loss, purpura
111
How do the neutrophils appear with megaloblastic anemia?
hypersegmented
112
Treatment of folate deficiency
1mg a day of folic acid supplemented with B12 if unsure of diagnosis to avoid neuropathy due to B12 deficiency
113
What are some important factors to absoprtion of B12?
R-B12 complex, IF-B12 complex, cubilin and amnion in transportation into enterocyte
114
Sources of B12
animal products, milk, eggs, cheese
115
Gastric disorders leading to B12 deficiency
total gastrectomy, blind loop syndrome, zollinger ellison syndrome; gastric producing tumors in pancrease secreting lots of HCL so B12 doesnt bind to IF, Ileal resection, malabsorption from hypothyroidism or drugs, tropical sprue, pancreatic insufficiency, vegans
116
What neurologic disorder is associated with B12 deficiency?
Early: parathesias, somulence and demetia, decreased vibratory and proprioreception
Late: paralysis from demyelination of dorsal and lateral columns, combined systemic disease
117
A lack of IF leads to _____.
pernicious anemia
118
____ is an autoimmune disease with insidious onset due to failure of IF secretion because of gastric mucosal atrophy.
pernicous anemia
119
Describe the pathogenesis of pernicous anemia.
CD4 T cells recognize receptors in secretory membrane. Antiparietal cell Ab in 90% of cases; IF Ab found in 50-70%
120
What test is performed when pernicious anemia is suspected?
schilling test
121
how is B12 deficiency treated?
give IM B12 for 2 wks
122
What type of sprue is associated with iron deficiency?
non-tropical
123
What type of sprue is associated with malabsorption of B12 and folate?
tropical
124
Hb ____ doesn't give up oxygen as easily.
fetal
125
What happens if there are no functional alpha globin chains?
death
126
What unique Hb are seen with Beta-Thal?
increased F and A2
127
What unique Hb are seen with alpha-thal?
Hb H, Bart's
128
Why are patients with B thalassemia anemic?
RBC die because of lack of Beta globin, causing hemolytic anemia and short-lived RBC. Blood transfusions can then cause iron overload.
129
Why do patients with T. major have distorted bones?
Bone marrow is extremely expanded and working super hard.
130
What clinical findings are seen the B-thalassemia major?
distorted bones, hepatomegaly, splenomegaly, hyperpigmentation, ulcers, cirrhosis of the liver, hepatocellular carcinoma
131
Why are pt with thalassemia hypercoaguable?
Membranes are damaged by alpha hemichromes and oxidative stress so that phosphotidlyserine is expressed on outer leaflet, targeting cell for apoptosis. This increases platelet activaion, hgb levels, and thrombin production.
132
Why do pt with thalassemia have endocrine and bone diseases?
hypogonadism, pituitary insuffieciency, osteopenia
133
Where is basophilic stippling seen?
thalassemia trait and major, hemolytic anemia, megaloblastic anemia,
134
Describe the diagnostic process for thalassemia?
family history, CBC, blood smear, physical exam (maybe normal), HPLC, PCR for alpha thal
135
What is hereditary persistence of fetal hemoglobin?
marked decrease in beta globin sytnthesis compensated by an increase in gamma chain synthesis.
136
_____ occurs 1%, as often as SS, and produces a favorable sickle syndrome.
S/HPFH
137
What is Hgb E disease?
Hgb E has a point mutation on beta globin that produces an unstable mRNA and beta-thal minor picture in homozygotes.
138
What is E/Beta- thal?
more common, 1 beta gene has mild-severe mutation and one has Hbg E mutation. Causes Thal minot to intermediate.
139
What is hemoglobin lepore?
normal alpha chains, a delta/beta fusion leads to thalassemia int. or major.
140
What kind of mutation usually causes beta thalassemia? Alpha?
Beta= point, alpha=deletion
141
Loss of 4 alpha genes=
gamma4. Bart's --> fetal death, hydrops fetalis
142
Loos of 3 alpha genes=
Hb H disease (Beta4)
143
Loss of 2 alpha genes=
trait
144
Loss of 1 alpha gene-
carrier
145
What is hemoglobin spring constant?
single base substitution in the terminal codon of alpha chain so that mRNA copies another 31 amino acids, making an unstable mRNA leading to market decrease in translation of alpha globin gene to protein. Moderately severe alpha thal clinical picture.
