Heme Definitions and Info Flashcards
(275 cards)
1
Q
rbc appearance
A
no nuclei, appearing as biconcave disks filled with hemoglobin
2
Q
neutrophil appearance
A
3-5 nuclear lobes with cytoplasm containing pale, iliac colored granules.
3
Q
neutrophils
A
they are phagocytes and protect against acute protection
4
Q
life span of neutrophils
A
5 hrs to a few days
5
Q
basophils appearance
A
lack a nuclear segment
6
Q
role of basophils
A
similar to eosinophils
7
Q
eosinophils appearance and role
A
2 nuclear lobes and play a role in chronic immune responses particularly those associated with helminth worm infections, asthma, and allergies
8
Q
what is largest wbc
A
monocyte
9
Q
monocyte appearance
A
kidney shaped nuclear and light blue cytoplasm
10
Q
monocyte role
A
similar to neutrophils and are highly phagocytic but long lived and serve as sentinels detecting danger signals produced by infection or tissue injury
11
Q
what is the key component in adaptive immune system
A
lymphocytes
12
Q
lymphocyte appearance
A
condensed nuclei and scant cytoplasm
13
Q
what may lymphocytes be
A
B cells, T cells, or natural killer cells
14
Q
B cells are formed where
A
bone marrow
15
Q
T cells are made where
A
thymus
16
Q
how many rbcs, platelets and neutrophils does the bone marrow produce every day
A
rbcs -> 200 billion
platelets -> 100 billion
neutrophils -> 60 billion
17
Q
why is hematopoiesis highly responsive to changes in peripheral counts
A
bc cytopenias and cytoses blood cells have serious even fatal consequences
18
Q
what is hematopoiesis maintained by
A
hematopoietic stem cells
19
Q
what is transplanted during a stem cell transplant
A
hematopoietic stem cells
20
Q
what does the clot formation start with
A
primary platelet plug
21
Q
what does the activation of platelets also result in and what is it converted to
A
arachidonic acid which is converted to thromboxane a2
22
Q
thromboxane a2
A
potent inducer of platelet via a series of enzymes including cyclooxygenase
23
Q
what does aspirin contain
A
cyclooxyrgenase inhibitors which is why aspiring is used to suppress platelet activation
24
Q
activation of platelets also causes it to release and activation of what
A
proteins that contribute to homeostasis such as platelet factor 4, fibrinogen and factor 5. activates factor xa receptor on the cell membrane of the platelet which joins with factor 5 to generate thrombin.
25
what does defects in coagulation or thrombolysis lead to
hypercoagulability or bleeding disorders
26
initial tests of blood coagulation cascade
platelet count
prothrombin time (pt)
partial thromboplastin time (ptt)
27
normal platelet count
> 100,000 per microliter
28
what happens if platelet count falls below 100,000
takes longer time to clot and usually comes with symptoms like purpura and mucosal bleeding
29
pt is a test of what pathway
extrinsic
30
what is a normal pt
10-13 secs
31
if pt is high what does it mean
deficiency in one or more of clotting factors in extrinsic pathway (VII, X V, prothrombin, fibrinogen).
32
inr is derived from what
pt
33
inr is the same as pt except
it is standardized by taking into account potency of tissues factor used
34
aptt is a test of what pathway
intrinsic
35
what is a normal ptt
25-35 secs
36
what is added to plasma which activates factor XII and starts intrinsic cascade
kaolin
37
intrinsic cascade
factors XII, XI, IX, VIII, X, V, prothrombin and fibrinogen.
38
tt
test of functionality of fibrinogen and presence of thrombin inhibitors
39
in inherited bleeding disorders how many deficiencies are present
single
40
in pts w/ acquired bleeding problem such as with liver disease or vitamin k deficiency how many deficiencies are present
multiple
41
labs in factor 5 & 10 or prothrombin defect
pt & ptt -prolonged
| tt - normal
41
labs in factor 5 & 10 or prothrombin defect
pt -pronlonged
42
labs in factor 7 defect
pt - prolonged
| ptt & tt - normal
43
labs in factor 12,11,9,8 defect
pt and tt- normal
| ptt - prolonged
44
labs in fibrinogen and thrombin inhibitor
pt and ptt- normal or prolonged
| tt- proloned
45
vitamin k antagonists
block or slow down clotting by affecting 7, 9, 10 and prothrombin bc they all need vitamin k for carboxylation
46
mc vit. k antagonist
warfarin
47
how to monitor pts on heparin and why
pt/inr testing to make sure the degree of anticoagulation is within therapeutic range
48
heparin
activates antithrombin and thus inhibits steps in cascade. IV.
49
low molecular weight heparin
sq heparin that does not require intensive monitoring but also doesn't work as rapidly
50
direct inhibitors
new oral anticoagulants that directly inhibit activated coagulation factors (in contrast to warfarin, which is indirect and affects the cascade)
51
three defects in clotting cascade
platelet function/thrombocytopenia
decrease in clotting factors due to decreased production or excess consumption
decrease in clotting factors because inherited defect
52
thrombocytopenia
too few platelets due to decreased platelet production or enhanced platelet destruction
53
platelet life span
7-9 days
54
platelet survival with decreased production
a week before severe thrombocytopenia occurred
55
platelet survival with destruction
curtails platelet survival suddenly and swiftly and can produce severe thrombocytopenia within hours
56
what does splenomegaly entail
high portion of platelets entrapped in spleen along with red and white blood cells
57
hypersplenism
reduction in one or more peripheral blood counts by splenic sequestration
58
platelet count of 50,000 to 120,00 which is not low enough to poser serious risk of hemorrhage
hypersplenidism
59
immune thrombocytoenic purpura (ITP)
immune mediated isolated thrombocytopenia caused by autoantibodies against platelets which leads to destruction of platelets
60
primary ITP
idiopathic, MC after viral infection
61
secondary ITP
immune mediated but associated w/ underlying disorders such as SLE, HIV, HCV
62
heparin induced thrombocytopenia
acquired within first 5-10 after initiation of heparin caused by autoantibody formation to the hapten of heparin & platelet factor which cause platelet activation and consumption leading to simultaneous thrombocytopenia and thrombosis.
63
disseminated intravascular coagulation (DIC)
activation of coagulation system leads to uncontrolled fibrin production due to tissue factor activation leading to widespread microthrombi which consumes coagulation proteins & platelets.
64
disseminated intravascular coagulation (DIC) etiologies
obstetric
infections (MC is gram negative sepsis)
malignancies (acute myelogenous leukemia, lung, GI or prostate malignancies)
65
what are bleeding disorders caused by
decrease in clotting factors due to decreased production or excess consumption
66
MCC of bleeding disorders
vitamin k deficiency/anticoagulation therapy
coagulopathy associated with liver disease
DIC can be considered excess consumption of clotting factors
67
what does vit k deficiency lead to
decrease in coagulation factors 2, 7, 9, 10 and the coagulation regulators protein c and s.
68
what is responsible for the carboxylation of factors 2, 7, 9, 10
vitamin k
69
what interferes with activation of vitamin k
warfarin
70
role of the liver
production and metabolism of coagulation factors
71
what can severe liver failure result in
bleeding tendency bc of factor deficiency
72
which factor is preserved in liver disease and where is it produced
factor 8 and in the endothelium
73
bleeding disorders caused by a decrease in clotting factors due to an inherited effect
hemophilia A & B
| Von Willebrand Disease
74
hemophilia a
inherited blood disorder most often associated with severe morbidity frequently requiring hospitalization
75
hemophilia a is due to deficiency of what factor
8
76
what kind of disorder is hemophilia a
x linked recessive
77
what % of pts have no family history and hemophilia a is due to spontaneous mutations
30%
78
hemophilia occurs in how male births
1/5000
79
pts w/ 1% or less factor 8 are considered what
severe and have average of 20-30 episodes per year of either spontaneous bleeding or excessive bleeding after minor trauma
80
if pt w/ 1-4% factor 8 they're considered
to have moderate hemophilia
81
if pt w/ 4% ir more factor 8 considered to have
mild hemophilia and generally have bleeding episodes only after trauma or surgery
82
hemophilia a life expectancy
60 yrs
83
leading cause of death among adult hemophilia pts
aids
84
hemophilia b
inherited bleeding disorder similar genetic, clinical, and molecular factors as hemophilia a
85
hemophilia b due to deficiency in
factor 9
86
where is the gene for factor 9 located and how im hemophilia b inherited
on X chromosome and inherited in x linked manner w/ female heterozygous carries passing the disease to half of sons
87
hemophilia b occurs in how many males
1/25000-30000
88
MC inherited bleeding disorder
von willebrand disease
89
von willebrand disease effects how many people
1/90 in US or 3 billion
90
how is von willebrand disease different from hemophilias
1. it is inherited is autosomal dominant way
2. bleeding is primarily from mm
3. bleeding time is prolonged
91
von willebrand disease caused by
mutations in the gene encoding von willebrand factor
92
functions of von willebrand factor protein
1. chaperones factor 8 protecting it from degradation
| 2. acts as molecular glue that enables platelets to adhere to injured blood vessels
93
what people have lower levels of plasma vWF and are commonly diagnosed a having von willebrand disease
humans with group O blood
94
type 1 von willebrand disease
vWF protein deficiencies and mc form (70%)
95
type 2 von willebrand disease
protein defects (not deficiencies) and accounts for 25% of cases
96
type 3 von willebrand disease
inherited a mutant vWF gene from each parent and proteins are very low so these pts have much more severe bleeding problems
97
thrombophilia
lab abnml that increase rick of venous thromboembolism and pts w/ hx of recurrent VTE, VTE at young age, strong fam hx of VTE or thrombosis at unusual site
98
virchows triad
abnml blood flow (stasis)
vessel injury or inflammation
hypercoagulability
99
common cause of acquired thrombophilia
antiphospholipid syndrome
100
acquired causes of thrombophilia
transient thrombophilia, including taking estrogen based contraception, pregnancy, cancer, surgery and immobilization
101
mc hereditary cause of thrombophilia
factor V leiden mutations and deficient of natural anticoagulants antithrombin, protein c, and protein s
102
about 1/2 of pts with hereditary thrombophilia have first thrombotic episode in relation to what
acquired prothrombotic risk factor
103
mc inherited cause of hyper coagulability
factor v leiden mutation
104
how much % of population effected by factor v leiden mutation
5%
105
factor v leiden mutation
genetic variant that increases activity of factor v bc it is resistant to breakdown by activated protein c
106
protein c or s deficiency
loss of function mutations that interfere w/ activity of inhibitors of coagulation rather than increasing activity if procoagulant factors.
107
protein c and s are ... dependent and produced in the ...
vit k, liver
108
anemia
lack of healthy rbcs or hemoglobin
109
causes of anemia
```
Hypoproliferative = Decreased production of RBCs or their components
Maturation = Inability of components to produce a healthy RBC or hemoglobin, often due to structural abnormality or deficiency of precursors
Hemolytic = destruction of RBCs or their components
```
110
how much hemoglobin in every rbc
280 mil
111
heme
protoporphyrin which binds to iron
112
where is heme synthesized
bone marrow (constant) but also liver (highly variable)
113
most famous heme protein synthesized by liver
cytochrome 450
114
what is heme synthesis regulated by
ALA synthase, prophobilinogen synthase and ferrochelatase
115
ALA synthase is regulated by
intracellular iron levels
116
Porphobilinogen and Ferrochelatase are inhibited by
Lead
117
each heme is capable of binding to
one O2 molecule
118
How many oxygen atoms does each hemoglobin carry?
8?
119
hemoglobin is made from
heme and globin (chains)
120
4 polypeptide globin chains
2 alpha chains and 2 non alpha chains
121
how many times of globin chains and what are they
alpha (α), beta (β), gamma (γ) and delta (δ)
122
alpha globin aa and chromosome
141 amino acids
| Coded on chromosome 16
123
beta globin aa and chromosome
146 amino acids
| Coded on chromosome 11
124
delta globin
small amounts in adults
125
gamma globin
found in fetal hemoglobin
126
Hemoglobin A (HgbA)
```
adult hemoglobin (aka hemoglobin α2β2)
97% of adult hemoglobin contains 2 α chains and 2 β chains.
```
127
Hemoglobin A2 (HgbA2)
less common form of adult hemoglobin
| 1-3% of adult hemoglobin contains 2 α chains and two delta (δ) chains.
128
Fetal hemoglobin (HgbF)
Has 2 α chains and 2 gamma (γ) chains that, by 6 months after birth, the γ chains evolve to β chains.
129
Hemoglobin S
predominant hemoglobin in people with sickle cell disease. The alpha chain is normal, the beta chain has a mutation (2 alpha chains, 2 beta S chains)
130
Hemoglobin H
a tetramer composed of four beta chains; seen in three-gene alpha thalassemia
131
Hemoglobin Barts
develops in fetuses with four-gene deletion alpha thalassemia
132
electrophoresis
A test to measure and identify the different types of hemoglobin in the blood. An electrical current separates normal and abnormal hemoglobin.
133
Hemolytic anemia
anemia caused by increased rbc destruction at rate that exceeds bone marrows ability to replace destroyed cells
134
what happens when there is rbc lysis
an intracellular enzyme called lactate dehydrogenase or LDH spills into plasma and builds up in blood
hemoglobin spills out of cell and breaks up into globin and heme
heme converted to bilirubin which is taken up by liver cells and secreted out with bile
135
inherited (intrinsic) hemolytic anemia
```
abnml rbcs
sickle cell
thalassemia
G6P6 deficiency
hereditary spherocytosis
```
136
extrinsic (acquired) hemolytic anemia
```
cause by things outside rbc
autoimmiune hemolytic anemia (AHA)
thrombocytopenic purpura (TTP)
hemolytic uremic syndrome (HUS)
paroxysmal nocturnal hemoglobinuria
```
137
hemoglobinopathies
defects in genes that control expression of hemoglobin proteins that produce abnormal hemoglobins and anemia
138
Structural defects in the hemoglobin molecule
alterations in the gene for one of the two hemoglobin subunit chains (alpha or beta) are called mutations. These mutations change a single amino acid in the subunit. These changes are often innocuous, but occasionally these disturb the behavior of the hemoglobin molecule and produce a disease state like Sickle Cell Anemia/Disease.
139
Diminished production of one of the two subunits of the hemoglobin molecule
Mutations that produce this condition are called “thalassemias.” Equal numbers of alpha and beta chains are necessary for normal function, but chain imbalances damage and destroy red cells and thereby produce anemia.
140
sickle cell trait homo or hetero
heterozygous
141
sickle cell disease
inherited disorder affecting beta globin gene leading to production of rbcs that sickle causing hemolysis and vase occlusive diease
142
cause of sickle cell anemia
replacement of glutamic acid w/ valine at position 6 on beta globin chain.
143
result of sickle cell disease
change in chains solubility. Deoxygenated hemoglobin S polymerizes to form twisted rope-like fibers that align and deform the RBC, producing the sickle shaped hemoglobin (HbgS).
144
sickle cells are destroyed by
spleen
145
what does sickle shape cause
vaso occlusion and hypoxia
146
when does clinical phenotype thalassemia become most apparent
at 6-9 months bc evolution from the gamma chains to adult chains occurs at around 6 months
147
alpha thalassemia mcc
gene deletions
148
Four phenotypes of alpha thalassemia
```
Silent Carrier (1 deletion) -> asymptomatic
Alpha Thalassemia Minor (2 deletions) -> causes mild microcytic anemia
Alpha Thalassemia Intermedia (3 deletions) -> presence of Hemoglobin H; Heinz bodies
Hydrops Fetalis (4 deletions) -> BART gammas; associated with stillbirth or death shortly after birth
```
149
beta thalassemia
decrease beta chain synthesis but most common are mutations that result in defective gene transcription or translation
150
three phenotypes of beta thalassemia
Beta Thalassemia Minor (1 mutation) -> asymptomatic or mild anemia
Beta Thalassemia Intermedia (mild homozygous form) -> mild anemia
Beta Thalassemia Major [AKA Cooley’s Anemia] (2 mutations) -> severe anemia
151
beta thalassemia major (Cooley's Anemia) risk factor
mediterranean descent
152
G6PD Deficiency
x linked recessive enzymatic disorders of rbcs that can cause hemolytic anemia
153
how much percent of african Americans have g6pd deficiency
10-15%
154
when is g6pd deficiency tested for
at birth
155
g6pd deficiency
G6PD activity is decreased during oxidative stress results in an oxidative form of Hb. The denatured hemoglobin precipitates as Heinz bodies.
RBC membrane damage and fragility causes extravascular RBC destruction in the spleen and liver.
156
G6PD deficiency exacerbated by
infections, fava beans, and some meds like (dapsone, Nitrofurantoin, “sulfa” drugs).
157
Hereditary spherocytosis (HS)
Autosomal dominant hereditary intrinsic hemolytic anemia caused by a deficiency in RBC membrane and cytoskeleton (spectrin/ankyrin). Most people with HS have a “silencing” of the ankyrin gene.
This leads to increased RBC fragility and sphere-shaped RBCs, which are detected and destroyed by the spleen (hemolysis).
158
extrinsic hemolytic anemias
antibodies and complement are directed against RBCs, leading to their destruction
159
extrinsic hemolytic anemias intravascular hemolysis
In some of these disorders, there’s excessive clot formation so when normal RBCs flow through these blood vessels, they get banged up and damaged, leading to intravascular hemolysis.
160
autoimmune hemolytic anemia can be divided into
IgG, also called warm antibody hemolytic anemia.
| IgM, also called cold agglutinin disease.
161
Extrinsic types can be further classified as ..... and ....
intravascular, meaning RBCs are destroyed within the vasculature, or extravascular, meaning that they are removed by macrophages in the spleen and liver.
162
Intravascular hemolysis
Hemoglobin that is released inside the vessels gets bound by a protein called haptoglobin and because they’re removed together, haptoglobin decreases.
When the haptoglobin gets consumed, the remaining hemoglobin goes via the blood through the kidneys and into the urine resulting in hemoglobinuria.
163
Extravascular hemolysis
RBCs are destroyed outside the vessels and so, haptoglobin is normal and there’s no hemoglobin or hemosiderin in the urine.
RBCs are usually destroyed in the spleen causing splenomegaly or the liver causing hepatomegaly.
164
Autoimmune hemolytic anemia
Acquired hemolytic anemia due to autoantibody production against RBCs.
165
Warm autoimmune hemolytic anemia and etiologies
IgG antibodies activated by protein antigens on the RBC surface at body temperature.
idiopathic (most common); medications (Penicillin, Cephalosporins, Rifampin, Phenytoin); autoimmune, viral infections, malignancy
166
cold autoimmune hemolytic anemia and etiologies
IgM antibodies against polysaccharides on the RBC surface induces intravascular, complement-mediated RBC lysis, especially at colder temperatures.
infection (EBV, HIV, Mycoplasma pneumoniae), malignancy, Waldenstrom macroglobulinemia
167
thrombotic thrombocytopenia purpura (TTP)
Thrombotic microangiopathy resulting from ADAMTS13 deficiency.
168
what is ADAMTS13
von Willebrand factor-cleaving protease.
169
what does ADAMTS13 deficiency lead to
to large vWF multimers that cause small vessel thrombosis.
170
Primary TTP
Primary = idiopathic (autoimmune) = antibodies against ADAMTS13
171
Secondary TTP
malignancy, bone marrow transplantation, SLE, pregnancy
172
Hemolytic uremic syndrome (HUS)
Thrombotic microangiopathy due to platelet activation by exotoxins.
173
Hemolytic uremic syndrome (HUS) risk factors
Predominately seen in children with a recent history of gastroenteritis
In adults it is associated with HIV, SLE, antiphospholipid syndrome or chemotherapy.
174
Hemolytic uremic syndrome (HUS) Triad
Thrombocytopenia
Hemolytic anemia
Renal dysfunction (uremia)
Fever and neurologic symptoms (seen in TTP) often absent in HUS
175
Hemolytic uremic syndrome (HUS) D+ HUS (classic)
diarrhea prodome. Exotoxins from Shigella or Enterohemorrhagic E. coli enters the blood where it damages vascular endothelium, activating platelets and eventually depleting platelets. The toxins preferentially damage the kidney, leading to uremia.
176
Hemolytic uremic syndrome (HUS) D- HUS (atypical)
not common; not associated with diarrhea
177
Hemolytic uremic syndrome (HUS) P- HUS
Streptococcus pneumonaia releases neuraminidase, which initiates an inflammatory reaction
178
Paroxysmal Nocturnal Hemoglobinuria
Rare, acquired (the PIGA gene) stem cell mutation where RBCs become deficient in GPI anchor surface proteins (CD55 & CD59)
CD55 & CD59 normally protect RBCs from compliment destruction. Deficiency in these proteins leads to increased complement activation and intravascular RBC destruction.
179
MC anemia worldwide
iron deficiency anemia
180
MCC of iron deficiency anemia in US
chronic blood loss
181
MCC of iron deficiency anemia in the world
decreased iron absorption
182
risk factors for iron deficiency anemia
Increased metabolic requirements = children, pregnant, lactating women
Cow milk ingestion in young children = infants or toddlers who are fed cow’s milk.
Cow’s milk has no iron
It makes it harder for the body to absorb iron
It can cause small bleeds in intestines
Children are full so they don’t eat other proteins with iron .
183
iron deficiency anemia
decreased rbc production bc there is a lack of iron and decreased iron stores (decreased ferritin).
184
lead poisoning
Lead poisons enzymes, including enzymes needed for heme synthesis.
Lead poisoning is most common in children (especially < 6) due to increased permeability of the blood-brain barrier as well as iron deficiency (may lead to increased iron absorption).
185
sources of lead poisoning
ingestion or inhalation of environmental lead (paint chips, lead dust -> lead was used in household paints prior to the 1970s).
186
anemia of chronic disease
Anemia due to decreased RBC production in the setting of chronic disease
It is seen in patients with chronic inflammatory conditions (autoimmune disorders, malignancy, etc.) It is caused by both hemolysis and failure of the erythropoietin response and a limitation in iron supply, which inhibit the marrow response. In addition, hepcidin (an acute phase reactant) blocks the release of iron from macrophages and reduces the GI absorption of iron.
187
anemia of chronic disease MC in who
It tends to be most common in patient with cancer, HIV infection, autoimmune diseases and patients with chronic kidney disease.
It is also more common in the elderly because of age-associated hematopoietic changes.
188
aplastic anemia
Pancytopenia with bone marrow hypocellularity
189
patho of aplastic anemia
T cells attack hematopoietic stem cells (HSC) or direct stem cell damage leads to bone marrow failure, including the replacement of marrow with fat.
190
MCC of aplastic anemia
radiation exposure
191
other cause of aplastic anemia
```
Infection = viral hepatitis, Parvovirus B19 in patients with baseline hemolytic anemias
Medications = antibiotics (Chloramphenicol, sulfa drugs), chemotherapy, anti-epileptics (Carbamazine, Phenytoin)
```
192
cause of severe aplastic anemia
Immune-mediated aplasia (failure of an organ or tissue to develop or function normally)
193
sources of b12
mainly animal in origin (meats, eggs, dairy)
194
patho fo b12 deficiency
B12 deficiency causes abnormal synthesis of DNA, nucleic acids and metabolism of erythroid precursors.
195
absorption of b12
B12 is released by the acidity of the stomach where it combines with intrinsic factor, where it is absorbed mainly in the distal ileum.
196
MMC of b12 deficiency
pernicious anemia, which is a lack of intrinsic factor because of parietal cell antibodies in the stomach, which causes decreased absorption of B12.
197
decreased b12 absorption also seen with
Crohn disease, celiac disease, chronic alcohol use.
Some drugs can decrease absorption, such as H2 blockers, PPIs, Metformin.
Can also be caused by decreased intake - mostly vegans who don’t eat meat products.
198
folate deficiency
abnormal synthesis of DNA, nucleic acids & metabolism of erythroid precursors.
199
folate stores only last
2-4 months
200
mcc of folate deficiency
inadequate intake
201
causes of folate deficiency
Increased requirements = pregnancy, infancy, hemolytic anemias, malignancy
Impaired absorption = celiac disease, inflammatory bowel disease, chronic diarrhea, anticonvulsants (Phenytoin, Carbamazepine)
Impaired metabolism due to drugs
202
hereditary hemochromatosis
Autosomal recessive disorder characterized by EXCESS IRON deposition in the parenchymal cells of the heart, liver, pancreas and endocrine organs.
203
hereditary hemochromatosis associated with what genotype
C282Y HFE
204
hereditary hemochromatosis patho
Mutation in the HFE protein leads to decreased hepcidin, the iron regulatory hormone.
Decreased hepcidin leads to increased intestinal iron absorption, leading to organ dysfunction from iron deposition in the parenchymal cells.
205
polycythemia vera (primary erythrocytosis)
Acquired myeloproliferative disorder with autonomous bone marrow overproduction of all three myeloid stem cell lines (primarily increased RBCs, but also increased granulocytic WBCs and platelets).
206
Primary (Polycythemia Vera)
normal O2 saturation, increased hematocrit, decreased erythropoietin, increased WBCs & platelets. This is due to a JAK gene mutation.
207
secondary polycythemia vera (primary erythrocytosis)
decreased O2 saturation, increased erythropoietin, normal WBC & platelets (this is usually seen with people who live at high altitudes, patients with COPD, etc.)
208
polycythemia vera (primary erythrocytosis) risk factors
Peaks 50-60 years of age; most common in men (60%)
209
what are blasts
early premature blood cells
210
presence of immature granulocytes in serum is sign of what
serious infection and the bone marrow is working hard to keep up with the high need for WBCs.
211
how many days do mature granulocytes spend in bone marrow before entering circulation and it can be shorted to what with severe infection
5-6 days to a day or less with release of immature granulocytes
212
The earliest response to an infection
emigration of granulocytes out of circulation and into the site of bacterial invasion. They trigger the full inflammatory response, which releases more cytokines capable of stimulating marrow-progenitor proliferation.
213
A mature neutrophil is called
"seg” or “segmented” cell.
214
An immature neutrophil is called
“band.”
215
Neutrophilia
increase in neutrophils beyond what is expected in a healthy individual.
216
Clinically, neutrophilia is defined as an absolute neutrophil count (ANC) in excess of
7,000 -7,500 /L. (Normal is 3,000 - 7,000).
217
The ANC is really an estimate of the body’s ability to
fight an infection.
218
Significant risk of bacterial sepsis
Grade IV = Severe = ANC < 500/uL
219
Grade I = Mild neutropenia
ANC 4,000 - 1,500/uL
220
Grade 2 = Mild neutropenia
ANC 1,499 - 1,000/uL
221
Grade 3 = Mod neutropenia
ANC 999 - 500/uL
222
Grade 4 = Severe neutropenia
ANC < 500/uL
223
cause of neutropenia
```
Autoimmune disease (SLE & RA are the most common)
Hypersplenism
HIV / AIDS
Hematopoietic malignancy
Leukemias
Hodgkin disease
T-cell malignancies
```
224
Myeloid
tissue of bone marrow
225
Myelogenous tissue
tissue arising from bone marrow
226
Myeloid disorders
disorders arising from the myeloid stem cells
227
Myeloproliferative disorders
group of conditions that cause blood cells (platelets, white blood cells, and red blood cells) to grow abnormally in the bone marrow.
228
myelodysplastic syndrome
Preleukemic disorders characterized by abnormal differentiation of cells of the myeloid cell line resulting in ineffective hematopoiesis in the bone marrow.
229
myelodysplastic syndrome risk factors
Age > 65 y
Hx of radiation therapy or chemotherapy
Benzene, mercury, or lead exposure; tobacco smoke
230
acute myeloid leukemia (aml)
malignancies that are characterized by the appearance of increased numbers of immature myeloid cells in the marrow and blood.
231
The fundamental oncogenic event of acute myeloid leukemia (aml)
takes place at the level of a very early progenitor cell, which results in a LEUKEMIC stem cell with self renewal and multipotential properties.
232
MC acute leukemia in adults
acute myeloid leukemia (aml)
233
acute myeloid leukemia (aml) patho
accumulation of leukemic blasts (immature WBCs) in the bone marrow, blood, or occasionally other tissues. Can cause pancytopenia.
234
acute myeloid leukemia (aml) age onset
65 y/o
235
Acute promyelocytic leukemia (APL or M3)
AUER rods, myeloperoxidase positive and associated with DIC.
236
Acute megakaryoblastic leukemia
most common in children < 5 y.o. w/ Down syndrome.
237
Acute monocytic leukemia
associated with gingival hyperplasia
238
three main types of aml
Acute promyelocytic leukemia (APL or M3).
Acute megakaryoblastic leukemia.
Acute monocytic leukemia.
239
Leukostasis
symptomatic hyperleukostasis = “blast crisis” seen in AML or CML
240
Leukostasis patho
super high levels of blast cells which leads to increased blood viscosity that clogs up the microvasculature, impeding tissue perfusion and causing local hypoxemia.
241
chronic myelogenous leukemia
myeloproliferative disorder of uncontrolled production of mature and maturing granulocytes.
In contrast to AML, they tend to have a more protracted clinical course as the malignant cells maintain the ability to mature during the chronic phase of the disease.
242
chronic myelogenous leukemia patho
Translocation between chromosomes 9 and 22 that results in a Philadelphia chromosome, which harbors a BCR-ABL1 fusion gene.
243
acute lymphocytic leukemia (all)
Malignancy arising from immature lymphoid stem cells in bone marrow.
244
MC childhood malignancy
acute lymphocytic leukemia (all)- peak 2-5 y/o more boys than girls
245
risk factor of acute lymphocytic leukemia (all)
down syndrome
246
MC acute lymphocytic leukemia (all)
B cell
247
acute lymphocytic leukemia (all) patho
overpopulation of immature WBCs (blasts) which overtake normal hematopoiesis, resulting in pancytopenia.
248
chronic lymphocytic leukemia (cll)
Malignancy of mature B-cells
249
MC form of leukemia in adults
chronic lymphocytic leukemia (cll)
250
chronic lymphocytic leukemia (cll) risk factors
increasing age (median = 70 y/o); men > women
251
multiple myeloma
Cancer associated with proliferation of a single clone of plasma cells, leading to increased production of ineffective monoclonal antibodies (especially IgG & IgA).
252
MC primary bone malignancy in adults
multiple myeloma
253
multiple myeloma risk factors
elderly > 65y, African American, male, benzene exposure
254
multiple myeloma patho
plasma cells accumulate in the bone marrow, interrupting bone marrow’s normal cell production. Protein accumulation causes kidney injury
255
Lymphoma
cancer where lymphocytes grow out of control.
256
hodgkin lymphoma
B-cell malignancy originating in the lymphatic system
257
peak of hodgkin lymphoma
at 20 y/o and again > 50 y/o
258
hodgkin lymphoma risk factors
Epstein-Barr virus, immunosuppression, smoking
259
four types of Hodgkin lymphoma
```
Nodular sclerosing (64%)
Mixed cellularity (25%)
Lymphocyte rich/predominant
Lymphocyte depleted (4%)
```
260
Nodular sclerosing (64%)
most common Hodgkins lymphoma type overall; female > male
261
Mixed cellularity (25%)
associated with EBV
262
Lymphocyte rich/predominant
most common in men < 35 y/o; best prognosis
263
Lymphocyte depleted (4%)
most common in males > 60 y/o; worst prognosis
264
non hodgkin lymphoma
Group of lymphocyte neoplasms with proliferation in the lymph nodes & spleen
265
non hodgkin lymphoma
```
Diffuse large B-cell
Follicular
Mantle cell
Marginal zone
Burkitt Lymphoma
Small lymphocytic
```
266
Diffuse large B-cell
Fast growing, aggressive
Middle age and elderly
Rapidly enlarging lymph nodes
MOST COMMOn
267
follicular
slow growing but hard to cute.
MC in adults
Painless lymphadenopathy.
2nd mc
268
mantle cell
poor prognosis
older adults
painless lymphadenopathy w/ GI liver involvement
small cells surrounding follicular zone "mantle"
269
marginal zone
small B cell hyperplasia from chronic immune/inflammatory states.
mucosal associated lymphoid tissue (malt) = gastric lymphomas
3 types:MALT, nodal, plenic
270
burkitt lymphoma
Intermediate B-cell proliferation; very aggressive but curable
peds/adolescent/HIV
extra nodal mass.
associated w/ EBV.
271
small lymphocytic
similar to cll
272
risk factors of non hodgkin lymphoma
Increased age
Immunosuppression: HIV, HCV, viral infection, organ transplant
Infections: EBV, HIV, H.pylori (with MALT), HHV-8 (Karposi Sarcoma)
Autoimmune disorders: SLE, dermatomyositis, RA, Hashimotos thyroiditis
273
tumor lysis syndrome
Oncologic emergency that can occur with the treatment of neoplastic disorders due to rapid tumor cell lysis after the induction of chemotherapy.
As the tumor cells lyse, they release massive amounts of potassium, phosphate and nucleic acids into the circulation.
274
risk factors for tumor lysis syndrome
High tumor burden (initial WBC count > 20,000 /uL), dehydration
Large proliferation rate (ALL) and high-grade lymphomas (Burkitt)
