HEMATOLOGY AND ONCOLOGY- Pathology Flashcards
1
Q
Alternative name for acanthocyte
A
Spur cell
2
Q
What does Acantho means?
A
spiny
3
Q
Associated pathology to Acanthocyte
A
Liver disease, abethalipoproteinemia states of cholesterol dysregulation)
4
Q
Which pathologies are associated to Achantocytes?
A
Anemia of chronic disease
Alchol Abuse
Lead poisoning
Thalassemias
5
Q
This type of cell is associated to G6PD deficiency
A
Bite cell
6
Q
When do we see elliptocyte?
A
Hereditary elliptocytosis
7
Q
Which atypic cells are seen in Megaloblastic anemia?
A
Hypersegmented PMNs
Macro- ovalocyte
8
Q
When are Macro ovalocyte seen?
A
Megaloblastic anemia and Marrow failure
9
Q
Which cells are characteristic of Sideroblastic anemia?
A
Ringed sideroblast
10
Q
Which is the basis of Sideroblastic anemia?
A
Excess iron in mitochondria= pathologic
11
Q
What explains Sideroblastic anemia?
A
The body has iron available but cannot incorporate it into hemoglobin, which red blood cells need to transport oxygen efficiently
12
Q
Altenative name for Schistocyte
A
Helmet cell
13
Q
When are Schistocytes seen?
A
DIC, Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic-Uremic Syndrome (HUS), traumatic hemolysis
14
Q
Example of Traumatic hemolysis that can cause Schistocytes
A
Mechanical heart valve prosthesis
15
Q
Which pathology is associated to Sickle cell?
A
Sickle cell anemia
16
Q
When are Spherocyte seen?
A
Hereditary spherocytosis
Autoimmune hemolysis
17
Q
When are Tear drop cells seen?
A
Bone marrow infiltration (eg myelofibrosis)
18
Q
Target cells are seen in…
A
HbC disease, Asplenia, Liver disease, Thalassemia
19
Q
What are Heinz bodies?
A
Are inclusions within red blood cells composed of denatured hemoglobin
20
Q
How are Heinz bodies form?
A
Oxidation of Hemoglobin sulfhydryl group → denatured hemoglobin precipitation and phagocytic damage to RBC membrane → bite cells
21
Q
Which stain is used to see Heinz bodies?
A
Crystal violet
22
Q
When are Heinz bodies seen?
A
In G6PD deficiency
23
Q
When are Heinz body-like inclussions seen?
A
In α thalassemia
24
Q
What are Howell Jolly bodies?
A
Basophilic nuclear remnants foun in RBCs
25
What is the normal process of Howell Jolly bodies?
Howel Jolly bodies are normally removed from RBCs by splenic macrophages
26
In these situations we could see Howell Jolly bodies
In patients with functional hyposplenia or asplenia
27
First step to classify an anemia
Microcytic
Normocytic
Macrocytic
28
What detemines Microcytic anemia?
MCV (
29
Pathologies associated to Microcytic anemia
Iron deficiency (late)
ACD (Anemia of Chronic Disease)
Thalassemias
Lead poisnoning
30
Which factors may first present as normocytic anemia and the progress to a microcytic anemia?
Iron deficiency
| Anemia of Chronic Disease
31
Which anemia is associated to Cooper deficiency?
Microcytic sideroblastic anemia
32
When is conseider Normocytic anemia?
MCV (50-100 fL)
33
How are Normocytic anemia classified?
Hemolytic
| Nonhemolytic
34
When is called Nonhemolytic anemia?
Reticulocyte count normal or ↓
35
Non hemolytic Normocytic Anemias
ACD (Anemia of Chronic Disease)
Aplastic anemia
Chronic kidney disease
Iron deficiency (early)
36
How is Hemolytic Anemia diagnose?
With Reticulocyte count ↑
37
How is Hemolytic Normocytic anemia classified?
Intrinsic
| Extrinsic
38
Intrinsic Hemolytic Normocytic anemias causes
RBC membrane defect (hereditary spherocytosis)
RBC enzyme deficiency (G6PD, pyruvate kinase)
HbC defect
Paroxysmal nocturnal hemoglobinuria
Sickle cell anemia
39
Extrinsic causes of Hemolytic Normocytic anemia
Autoimmune
Microangiopathic
Macroangiopathic
Infections
40
When is diagnose Macrocytic anemia?
MCV (>100 fL)
41
How are Macrocytic anemia classified?
Megaloblastic and non Megaloblastic
42
Megaloblastic anemias causes
Folate deficiency
B12 deficiency
Orotic aciduria
43
Causes of Non megaloblastic anemias
Liver disease
Alcoholism
Reticulocytosis
44
Which kind of anemia does Iron deficiency causes?
Microcytic, hypochromic anemia
45
Pathophysiology of Iron deficiency anemia
↓ iron due to chronic bleeding, malnutrition/absorption disorders or ↑ demand → ↓ final step in heme synthesis
46
Causes of iron deficiency due to chronic bleeding
GI loss
| Menorrhagia
47
Causes of iron deficiency due to increase demand
Pregnancy
48
How are the labs in iron deficiency?
↓ iron
↑ Total iron-binding capacity
↓ ferritin
49
Clinical findings of iron deficiency
Fatigue
| Conjuntival pallor
50
In microscope what are the findings?
Microcytosis and hypochromia
51
How can iron deficiency anemia may manifest?
Plummer Vinson syndrome
52
Characteristic of Plummer Vinson syndrome
Triad of iron deficency anemia, esophageal webs, atrophic glossitis
53
What is the defect in α Thalassemia?
α globin gene deletions → ↓ α globin synthesis
54
Types of deletion in α Thalassemia
Cis deletion
| Trans deletion
55
Who suffer more cis deletion in α Thalassemia?
Asian population
56
In whom is more prevalent trans deletion of α thalassemia?
African population
57
Charactetistics of 4 allele deletion in α Thalassemia
No α-globin
| Excess γ globin forms γ4
58
What is Hb Barts?
Excess γ globin forms γ4
59
Which kind of deletion in α Thalassemia is incompatible with life? Why?
4 allele deletion
| Causes allele deletion
60
Which disease is caused by 3 allele α Thalassemia?
HbH disease
61
Characteristics of 3 allele α Thalassemia
Very little α globin
| Excess β globin forms β4
62
What does Excess β globin causes?
HbH disease
63
What is the effect of 1-2 allele deletion in α Thalassemia?
No clinically significant anemia
64
Which kind of Anemia is β Thalassemia?
Microcytic, hypochromic anemia
65
What happens in β Thalassemia?
Point mutations in splice sites and promoter sequences→ ↓ β globin synthesis
66
In whom is more prevalent β thalassemia?
In mediterranen populations
67
Classification of β thalassemia
β thalassemia minor
β thalassemia major
HbS/ β thalassemia heterozygote
68
How else is β thalassemia minor known?
Heterozygote
69
How is β chain in β thalassemia minor?
Underproduced
70
Symptoms of β thalassemia minor
Usually asymptomatic
71
How is β thalassemia minor diagnosis confirmed?
By ↑ HbA2 (>3.5%) on electrophoresis
72
Alternative name for β thalassemia major
Homozygote
73
What is affected in β thalassemia major?
β chain is absent
74
How is anemia consider in β thalassemia major?
Severe anemia
75
What is required in β thalassemia major?
Blood transfusion
76
What could be the result of β thalassemia major?
Hemochromatosis due to requiring constant blood transfussions
77
Findings of β thalassemia major
Marrow expansion → Skeletal deformitis
| "Chipmunk" facies
78
How is marrow expansion seen in β thalassemia major?
"Crew cut" on skull x ray
79
Complication of β thalassemia major
Extramedullary hematopoiesis (leads to hepatosplenomegaly)
80
From which microorganism is increased the risk of aplastic crisis in β thalassemia major?
Parvovirus B19 induced aplastic crisis
81
Structuraly how is HbF composed?
α2γ2
82
Type of Hb increased in β thalassemia major
Increased HbF
83
What is the benefict of increased HbF in β thalassemia major?
HbF is protective in tje infant and disease only becomes symptomatic after 6 months
84
Characterteristics of HbS/ β thalassemia heterozygote
Mild to moderate sickle cell disease depending on amoun of β globin production
85
What kind of anemia is produced by lead poisoning?
Microcytic, hypochromic anemia
86
Pathophysiology of Lead poisoning anemia
Lead inhibits ferrochelatase and ALA (Porphobilinogen synthase or ALA dehydratase, or aminolevulinate) → ↓ heme synthesis and ↑ RBC protoporphyrin
87
What other problem does Lead poisoning causes in RBC?
Also inhibits rRNA degradation, causing RBCs to retain aggregates of rRNA (basophilic stippling)
88
Risk factor that increases Lead poisoning
In Old houses with chipped paint
89
Findings of Lead poisoning
LEAD:
Lead lines on gingivae (Burton lines) and on methaphyses of long bones on x-ray
Encephalopathy and Erythrocyte basophilic stippling
Abdominal colic and sideroblastic Anemia
Drops- Wrist and foot drop
90
First line of treatment related to wrist and foot drop caused by lead poisoning
Dimercaprol and EDTA (Ethylenediaminetetraacetic acid)
91
In Lead poisoning what is the treatment for kids?
Succimer used for chelation for kids
92
Anemia caused by Sideroblastic anemia
Microcytic anemia, hypochromic
93
What is the problem of Sideroblastic anemia?
Defect in heme synthesis
94
Hereditary explanation of Sideroblastic anemia
X linked defect in δ ALA synthase gene
95
Causes of Sideroblastic anemia
Genetic
Acquired
Reversible
96
Causes of Acquired Sideroblastic anemia
Myelodysplastic syndromes
97
Reversible causes of sideroblastic anemia
```
Alcohol is most common
Lead
vitamin B6 deficiency
Cooper deficiency
Isoniazid
```
98
Microscopic findings in Sideroblastic anemia
Ringed sideroblasts (with iron laden mitochondria) seen in bone marrow
99
Labs found ins Sideroblastic anemia
↑ iron, normal TIBC, ↑ ferritin
100
Treatment for sideroblastic anemia
Pyridoxine
101
Why is Pyridoxine administer for sideroblastic anemia?
Because B6 cofactor for δ ALA synthase
102
Pathophysiology of Megaloblastic anemia
Impaired DNA synthesis → maturation of nucleus of precursor cells in bone marrow delayed relative to maturation of cytoplasm
103
What could be one of the final results of Megaloblastic anemia?
Abnormal cell division→ pancytopenia
104
Causes of Folate deficiency causing Megaloblastic anemia
Malnutrition (eg, alcoholics), malapsorption, antifolates, Increased requirements
105
Antifolates drugs
Methotrexate
Trimethoprim
Phenytoin
106
Situations that increase Folate requirements?
Hemolytic anemia
| Pregnancy
107
Findings in Folate deficiency
Hypersegmented neutrophils, glossitis, ↓ folate, ↑ homocysteine but normal methylmalonic acid
108
What clinical finding distinguish folate deficiency from vitamin B12 deficiency?
No neurologic symptoms in folate deficiency
109
Alternantive name for vitmain B12
Cobalamin
110
Causes of vitmain B12 deficiency
Insufficient intake (strict vegans), malabsorption (eg. Crohn disease), pernicious anemia, Diphyllobothrium latum (fish tapeworm), proton pump inhibitors
111
Findings of Vitamin B12 deficiency
Hypersegmented neutrophils, glossitis, ↓ B12, ↑ homocysteine, ↑ methylmalonic acid
112
Neurologic symptoms of Vitamin B12 deficiency
```
Peripheral neuropathy with sensoriomotor disfunction
Dorsal columns (vibration/ propioception)
Lateral corticospinal (spasticity)
Dementia
```
113
Characteristics of Neurologic symptoms caused by Cobalamin deficiency
Subacute combined degeneration
114
What explains Subacute combined degeneration in Vitmain B12 deficiency?
Due to involvement of B12 in fatty acid pathways and myelin sinthesis
115
What kind of anemia does Orotic aciduria cause?
Megaloblastic anemia
116
Pathophysiology of Orotic aciduria
Inability to convert orotic acid to UMP because of defect in UMP synthase
117
In which process do we see the conversion from Orotic acid to UMP?
De novo pyrimidine synthesis pathway
118
Inheritance mode of Orotic aciduria
Autosomal recessive
119
In Whom is Orotic aciduria suspected? and how?
presents in children as megaloblastic anemia that canot be cured by folate or B12 with failure to thrive
120
Which deficiency could be compared with Orotic aciduria?
Orhithine transcarbamylase deficiency
121
What difference is classic in Orotic aciduria compared to Orhithine transcarbamylase deficiency?
No hyperammonemia in Orotic aciduria
| Orhithine transcarbamylase deficiency presents with Increased orotic acid with hyperammonemia
122
Findings of Orotic Aciduria
Hypersegmented neutrophils, glossitis, orotic acid in urine
123
Treatment for Orotic Aciduria
Uridine monophosphate to bypass mutated enzyme
124
Main characteristic of Nonmegaloblastic macrocytic anemias
Macrocytic anemia in which DNA synthesis is unimpaired
125
Causes of Nonmegaloblastic macrocytic anemias
Liver disease
Alcoholism
Reticilocytosis
Drugs
126
Drugs that could cause Macrocytic anemias
5 FU
Zidovudine
Hydroxyurea
127
Findings of Intravascular hemolysis in Normocytic, normochromic anemias
↓ haptoglobin, ↑ LDH, schistocytes and ↑ reticulocytes on peripheral blood smear; and urobilinogen in urine
128
Examples of Intravascular hemolysis in Normocytic, normochromic anemias
Paroxysmal nocturnal hemoglobinuria
Mechanical destruction (aortic stenosis, prothetic valve)
Microangiopathic hemolytic anemia
129
Findings of extravascular hemolysis in Normocytic, normochromic anemias
Macrophages in spleem clears RBC
Spherocytes in peripheral smear, ↑ LDH plus ↑ unconjugated bilirubin, which causes jaundice (eg. hereditary spherocytosis)
130
Pathophysiology of Anemia of chronic disease
Inflammation → ↑ Hepcidine → ↓ release of iron from macrophages
131
What is the effect of Increased Hepcidin? and who releases it?
Released by liver, binds ferroportin on intestinal mucosal cells and macrophages , thus inhibiting iron transport
132
Lab Findings of Anemia of chronic disease
↓ iron, ↓ TIBC, ↑ ferritin
133
What could be the final stage of Anemia of chronic disease?
Can become microcytic, hypochromic
134
At the begining what type of anemia is Anemia of chronic disease
Nonhemolytic, normocytic anemia
135
What kind of anemia is Aplastic anemia?
Nonhemolytic, normocytic anemia
136
What causes Aplastic anemia?
By failure or destruction of myeloid stem cells
137
What causes destructuin of myeloid stem cells?
Radiation and drugs
Viral agents
Fanconi anemia
Idiopathic; may follow acute hepatitis
138
Drugs that can cause aplastic anemia
Benzene
Chloramphenicol
Alkylating agents
Antimetabolites
139
Viral agents related to Aplastic anemia
Parvovirus B19
EBV
HIV
HCV
140
What is the defect in Fanconi anemia?
DNA repair defect
141
What is the cause of idiopathic aplastic anemia?
Immune mediated, primary stem cell defect
142
Findings in Aplastic anemia
Pancytopenia, characterized by sever anemia, leukopenia, and thrombocytopenia
Normal cell morphology, but hypocellular bone marrow with fatty infiltration (dry bone marrow tap)
143
Symptoms of Aplastic anemia
Fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection
144
Possible treatment fot Aplastic anemia
Withdrawal of offending agent, immunosuppressive regimens, allogeneic bone marrow transplantation, RBC and platelet transfusion, G-CSF, or GM-CSF
145
Immunosuppressive regimens used in Aplastic anemia
Antithymocyte globulin
| Cyclosporine
146
How does Chronic Kidney disease causes Nonhemolytic, normocytic anemia?
↓ EPO → ↓ hematopoiesis
147
Types of Intrinsic normocytic anemias
Extravascular
| Intravascular
148
What kind of anemia is Hereditary spherocytosis?
Intrinsic normocytic anemias, Extravascular
149
What is the defect in Hereditary spherocytosis?
Defect in proteins interacting with RBC membrane skeleton and plasma membrane
150
Types of defects in proteins intertacting with RBC membrane skeleton and plasma membrane in Hereditary spherocytosis
Ankyrin, band 5, protein 4.2, spectrin
151
In hereditary spherocytosis, what happens if RBC has less memebrane?
Causes small and round RBCs with no central pallor → premature removal of RBCs by spleen
152
Which labs are identifiy in small and round RBCs?
↑ MHCH, ↑ red cell distribution width
153
Clinical findings of Hereditary spherocytosis
Splenomegaly, aplastic crisis (parvovirus B19 infection)
154
Labs found in Hereditary spherocytosis
Osmotic fragility test +
| Normal to ↓ MCV with abundance of cells; masks microcytia
155
What screening test is useful for Hereditary spherocytosis?
Eosin 5 maleimide binding test
156
Treatment for Hereditary spherocytosis
splenectomy
157
What kind of anemia is G6PD deficiency?
Intrinsic normocytic anemias, Intravascular/Extravascular
158
Most common enzymatic disorder of RBCs
G6PD deficiency
159
Inheritance mode of G6PD deficiency
X linked recessive
160
Pathophysiology of G6PD deficiency
Defect in G6PD → ↓ glutathione → ↑ RBC susceptibility to oxidant stress
161
Classic causes of Hemolityc anemia following oxidant stress
Sulfa drugs, antimalarials, infections, fava beans
162
Clinical findings of G6PD deficiency
Back pain, hemoglobinuria a few days after oxidant stress
163
Labs found in G6PD deficiency
blood smear shows RBCs with Heinz bodies and bite cells
164
How is Pyruvate kinase deficiency classified?
Intrinsic hemolytic normocytic anemia, Extravascular
165
Inheritance mode of pyruvate kinase deficiency
Autosomal recessive
166
Pathophysiology of pyruvate kinase deficiency
Defecct in pyruvate kinase → ↓ ATP → rigid RBCs
167
How is pyruvate kinase deficiency diagnose?
Hemolytic anemia in a newborn
168
What kind of anemia is HbC defect?
Intrinsic hemolytic normocytic anemia, Extravascular
169
Pathophysiology of HbC defect
Glutamic acid to lysine mutation at residue 6 in β globin
170
Which has milder disease between HbSC and HbSS patients?
Patients with HbSC (1 of each mutant gene) have milder disease than have HbSS patients
171
What type of anemia is Paroxysmal nocturnal hemoglobinuria?
Intrinsic hemolytic normocytic anemia, Intravascular
172
Pathophysiology of Paroxysmal nocturnal hemoglobinuria
↑ complement- mediated RBC lysis
173
What is happens when ↑ complement- mediated RBC lysis during Paroxysmal nocturnal hemoglobinuria?
Impaired synthesis of GPI (glycosylphosphatidylinositol) anchor from decay accelerating factor that protects RBC membrane form complement
174
How is Paroxysmal nocturnal hemoglobinuria acquired?
Acquired mutation oin a hematopoietic stem cell
175
What risk is increased with Paroxysmal nocturnal hemoglobinuria ?
Increased incidence of acute leukemias
176
Triad of Paroxysmal nocturnal hemoglobinuria
Coombs - hemolytic anemia
Pancytopenia
Venous thrombosis
177
Labs found in Paroxysmal nocturnal hemoglobinuria
CD55/59 - RBCs on flow cytometry
178
Treatment for Paroxysmal nocturnal hemoglobinuria
Eculizumab
179
How is Sickle cell anemia classify?
Intrinsic hemolytic normocytic anemia, Extravascular
180
Causes a single amino acid replacement in β chain at position 6
HbS point mutation
181
What is subtitute in HbS point mutation?
Glutamic acid with valine
182
Pathogenesis of Sickle cell anemia
Low O2, dehydration, or acidosis precipitates sickling (deoxygenated HbS polymerizes), which results in anemia and vaso- occlusive disease
183
Why are Newborns are asymptomatic with sickle cell anemia?
Because of ↑HbF and ↓ HbS
184
From which infection do sickle cell anemia patients have resistance?
Heterozygotes (sickle cell trait) have resistance to malaria
185
Who carry HbS trait in Sickle cell anemia?
8% of African Americans carry the HbS trait
186
Which form do Sickle cell anemia have?
Sickle cells are crescent shaped RBCs
187
What is seen on X ray in sickle cell anemia?
"Crew cut" on skull x ray due to marrow expansion from ↑ erythropoiesis
188
Which pathologies present with "Crew cut" on skull x ray?
Sickle cell anemia and Thalasemias
189
Complications of Sickle cell anemia?
```
Aplastic crisis (due to Parvovirus B19)
Autosplenectomy
Splenic sequestration crisis
Salmonella osteomyelitis
Painful crisis
Renal papilary necrosis and Microhematuria
```
190
What is seen in Autosplenectomy caused by sickle cell anemia?
Howell Jolly bodies
191
What could be the results of Autosplenectomy in sickle cell anemia?
↑ risk of infection with encapsilated organisms
192
What happens in childhood in patients with sickle cell anemia?
Early splenic dysfunction
193
What causes painful crisis in Sickle cell anemia?
```
Vaso-occlusive
Painful hand swelling
Acute chest syndrome
Avascular necrosis
Stroke
```
194
What happens when vaso occlusive is present in sickle cell anemia?
Dactylitis
195
Most common cause of death in adult related to Sickle cell anemia
Acute chest syndrome
196
What is the cause of Renal papillary necrosis?
Due to low O2 in papilla, also seen in heterozygotes
197
In Sickle cell anemia patients, what causes microhematuria?
Medulalry infarcts
198
How is Sickle cell anemia diagnose?
Hemoglobin electrophoresis
199
Treatment of Sickle cell anemia?
Hydroxyurea and bone marrow transplantation
200
What happens when administer hydroxyurea in sickle cell anemia?
↑ HbF
201
Autoimmune hemolytic anemia is consider...
Extrinsic hemolytic normocytic anemia
202
How is Autoimmune hemolytic anemia classify?
Warm agglutinin
| Cold aglutinin
203
What is the most common cause of warm and cold algutinin Autoimmune hemolytic anemia?
Idiopathic in etiology
204
Which immunoglobulin represents Warm agglutinin Autoimmune hemolytic anemia?
IgG
205
What pathologies are related to Warm agglutinin Autoimmune hemolytic anemia?
Chronic anemia seen in SLE, CLL, or with certain drugs
206
Example of drug that can cause Warm agglutinin Autoimmune hemolytic anemia
α methyldopa
207
Immunoglobulin that represents Cold agglutinin Autoimmune hemolytic anemia
IgM
208
What is the factor related to Cold agglutinin Autoimmune hemolytic anemia?
Acute anemia triggered by cold
209
Pathologies related to Cold agglutinin Autoimmune hemolytic anemia
Mycoplasma pneumonia infections, or infectious mononucleosis
210
Which lab test is usually positive in Autoimmune hemolytic anemia?
Coombs +
211
Characteristics of Direct Coombs test
Anti Ig antibody (Coombs reagent) added to patient's blood
212
When is Direct Coombs test positive?
RBCs agglutinate if RBCs are coated with Ig
213
What happens in Indirect Coombs test?
Normal RBCs added to patients serum. If serum has anti Ig antibodies (Coombs reagent) added
214
What kind of anemia is Microangiopathic anemia?
Extrinsic hemolytic normocytic anemia
215
Pathogenesis of Microangiopathic anemia
RBCs are damaged when passing through obstructed or narrowed vessel lumina
216
When is Microangiopathic anemia seen?
In DIC, TTP-HUS, SLE amd malignant hypertension
217
Which cells are seen in Microangiopathic anemia?
Schistocytes (helmet cells) are seen on blood smear due to mechanical destruction of RBCs
218
How is Macroangiopathic anemia consider?
Extrinsic hemolytic normocytic anemia
219
Prosthetic heart valves and aortic stenosis may cause these types of anemia
Macroangiopathic anemia
| Hemolytic anemia secondary to mechanical destruction
220
Cells seen in Macroangiopathic anemia
Schostocytes on peripheral blood smear
221
Which anemia is cause by infections?
Extrinsic hemolytic normocytic anemia
222
Examples of agents that cause infectious anemia
Malaria
| Babesia
223
What happens in Infectious anemia?
↑ destruction of RBCs
224
Importance of ferritin
Primary iron storage protein of body
225
Transport iron in blood
Transferrin
226
In which situation is Serum iron decrease?
```
Iron deficiency (primarily)
Chronic disease
```
227
In this disease Serum iron is increased
Hemochromatosis (primarily)
228
Which lab indirectly measures Transferrin?
TIBC (Total iron-binding capacity)
229
Situation in which Transferrin is increase
Iron deficiency
| Pregnancy/ OCP use (primarily)
230
Situations when Transferrin production is increased
Pregnancy/ OCP use
231
When is Transferrin decreased?
Chronic disease
| Hemochromatosis
232
In which pathologies is ferritin increased?
```
Chronic disease (primarily)
Hemocromatosis
```
233
When is ferritin decreased?
Iron Deficiency
234
How is % transferrin saturation in Iron deficiency?
↓↓
235
How is % transferrin saturation in Hemochromatosis?
↑↑
236
How is % transferrin saturation in prenancy and OCP use?
↓
237
How is % transferrin saturation calculated?
Serum iron/ Total iron-binding capacity (TIBC)
238
Types of Leukopenias
Neutropenia
Lymphopenia
Eosinopenia
239
When is consider Neutropenia?
Absolute neutrophil count
240
Causes of Neutropenia
Sepsis/ postinfection, drugs (including chemotherapy), aplastic anemia, SLE, radiation
241
How is Lymphopenia consider
Absolute lymphocyte count
242
Which Lymphocyte count are require in children to be classified as lymphopenia?
Absolute lymphocyte count
243
Pathologies that cause lymphopenia
HIV
| DiGeorge syndrome, SCID (severe combined immunodeficiency), SLE, corticosteroids, radiation , sepsis, postoperative
244
Causes of Eosinopenia
Cushing syndrome, corticosteroids
245
How do Corticosteroids affect Leukocytes?
Cause neutrophilia, but eosinopenia and lymphopenia
246
What is the effect of Corticosteroids to Neutrophils?
↓ activation of neutrophil adhesion molecules, imparing migration out of the vasculature to sites of inflammation
247
What is the effect of corticosteroids to Eosinophils?
Sequester eosinophils in lymph nodes
248
What is the effect of corticosteroids to Lymphocytes?
Cause apoptosis
249
What are porphyrias?
Are hereditary or acquired conditions of defective heme synthesis that lead to the accumulation of heme precursors
250
What happens in lead poisoning?
Lead inhibits specific enzynes needed in heme synthesis, leading to similar conditions to Porphyrias
251
Which is the affected enzyme in lead poisoning?
Ferrochelatase and ALA dehydrate
252
What is the accumulated substrate in Lead posisoning?
Protoporphyrin, δ ALA (blood)
253
Presenting symptoms of Lead poisoning
Microcytic anemia, GI and kidney disease
254
How do children get Lead poisoning?
Exposure to lead paint
255
Clinical manifestation of Lead poisoning in children
Mental deterioration
256
How do Adults acquired Lead poisoning?
Enviromental expossure (battery/ ammunition/ radiator factory)
257
Clinical pressentation of Lead poisoning in adults
Headache, memory loss, demyelination
258
Porphobilinogen deaminase is the affected enzyme in this pathology
Acute intermittent deaminase
259
Which enzyme is affected in Acute intermittent deaminase?
Porphobilinogen deaminase
260
Accumulated substrate in Acute intermittent deaminase
Porphobilinogen, δ ALA, coporphobilinogen (urine)
261
Symptoms of Acute intermittent deaminase
```
5 P's:
Painful abdomen
Port wine-colored urine
Polyneuropathy
Psychological disturbances
Precipitated by drugs, alcohol, and starvation
```
262
Treatment for Acute intermittent deaminase
Glucose and heme, which inhibit ALA synthase
263
Uroporphyrinogen decarboxylase is the affected enzyme in this pathology
Porphyria cutanea tarda
264
What enzyme is affected in Porphyria cutanea tarda?
Uroporphyrinogen decarboxylase
265
Accumulated substrate in Porphyria cutanea tarda
Uroporphyrin (tea- colored urine)
266
Presenting symptom of Porphyria cutanea tarda
Blistering cutaneous photosensitivity
267
Most common porphyria
Porphyria cutanea tarda
268
When is ALA synthase activity increased?
↓ heme
269
When is ALA synthase activity decreased?
↑ heme
270
What does PT test?
Test function of common and extrinsic pathway
271
Test function of common and extrinsic pathway
PT test
272
Which factors are part of extrinsic pathway?
I, II, V, VII and X
273
Test function of common and intrisic pathway
PTT
274
What does PTT evaluates?
Test function of common and intrinsic pathway
275
Which factors are part of intrinsic pathway?
All factors except VII and XIII
276
When extrinsic and common pathway have a defect, how is manifested?
↑ PT
277
When is PT increased?
In extrinsic and common pathway defects
278
When intrinsic and common pathway have a defect, how is manifested?
↑ PTT
279
When is PTT increased?
In intrinsic and common pathway defects
280
Which coagulation times are alterated in hemophilia A or B?
↑ PTT
281
How is hemophilia A or B classified?
Intrinsic pathway coagulation defect
282
What is deficient in hemophilia A?
Deficiency of factor VIII
283
Which labs are abnormal in Hemophilia A?
↑ PTT
284
What is deficient in hemophilia B?
Deficiency of factor IX
285
Which labs are abnormal in Hemophilia B?
↑ PTT
286
Clinical presentation of Hemophilia A or B
Macrohemorrhage in hemophilia- hemarthroses, easy bruising, ↑ PTT
287
What is hemarthroses?
Bleeding into joints
288
Treatment for Hemophili A
Recombinant factor VIII
289
Which labs are abnormal in Vitamin K deficiency?
↑ PTT, ↑ PT
290
How is Vitamin K consider?
General coagulation defect
291
How is the bleeding time in Vitamin K deficiency?
Normal
292
What is affected in Vitamin K deficiency?
↓ synthesis of factors II, VII, IX, X, protein C, protein S
293
How is defect in platelet plug formation manifested?
↑ bleeding time
294
How is platelet abnormalitie manifested?
Microhemorrhage: mucous membrane bleeding, epistaxis, petechiae purpura, ↑ bleeding time, possible ↓ platelet count
295
How is Platelet count and Bleeding time in Bernard Soulier syndrome?
PC ↓ and BT ↑
296
Platelet disorders
Bernard Soulier syndrome
Glanzmann thrombasthenia
Immune thrombocytopenia
Thrombotic thrombocytopenia purpura
297
What is the problem in Bernard Soulier syndrome?
Defect in platelet plug formation
298
This syndrome is characterized by ↓ GpIb
Bernard Soulier syndrome
299
What is the consequence of ↓ GpIb?
Defect in platelet to vWF adhesion
300
What is seen in Bernard Soulier syndrome?
Defect in platelet to vWF adhesion
301
What is the main point in Glanzmann thrombasthenia?
Defect in platelet plug formation
302
Which lab is affected in Glanzmann thrombasthenia?
Increased bleeding time, normal platelet count
303
Syndrome Characterized by ↓ GpIIb / IIIa
Glanzmann thrombasthenia
304
What is affected with ↓ GpIIb / IIIa?
Defect in platelet to platelet aggregation
305
What is seen in Glanzmann thrombasthenia blood smear?
Shows no platelet clumping
306
Labs found in Immune thrombocytopenia
↓ Platelet count
| ↑ Bleeding time
307
What is the defect in immune thrombocytopenia?
Anti GpIIb/IIIa antibodies
308
What is the result of Anti GpIIb/IIIa antibodies?
Splenic macrophage consumption of platelet/antibody complex
309
What may triggers immune thrombocytopenia?
By viral illness
310
What is the effect of immune thrombocytopenia in platelets?
Decreased platelet survival
311
Finding of immune thrombocytopenia
Increased megakaryocytes on bone marrow biopsy
312
Lab findings in thrombotic thrombocytopenic purpura
↓ Platelet count
| ↑ Bleeding time
313
What is the explanation of thrombotic thrombocytopenic purpura?
Inhibition or deficiency of ADAMTS 13 (vWF metalloprotease)
314
What is the result of Inhibition or deficiency of ADAMTS 13 (vWF metalloprotease)?
↓ Degradation of vWF multimers
315
Pathogenesis of thrombotic thrombocytopenic purpura
↑ large vWF multimers →↑ platelet adhesion → ↑ platelet aggregation and thrombosis
316
What is the final result of thrombotic thrombocytopenic purpura?
↓ Platelet survival
317
Labs found in thrombotic thrombocytopenic purpura
Schistocytes, ↑ LDH
318
Symptoms of thrombotic thrombocytopenic purpura
Pentad of neurologic and renal symptoms, fever, thrombocytopenia, and microangiopathic hemolytic anemia
319
Treatment for thrombotic thrombocytopenic purpura
Exchange transfusion and steroids
320
Labs affected in von Willebrand disease
Increase bleeding time
| Normal or increased PTT
321
Defects in von Willebrand disease
Intrinsic pathway coagulation defect
| Defect in platelet plug formation
322
What is the result of ↓ vWF in Intrinsic pathway coagulation defect?
Normal or ↑ PTT (depends on severity; vWF acts to carry/ protect factor VIII)
323
What explains decrased of vWF lead to increased PTT?
vWF acts to carry/ protect factor VIII
324
What is the result of ↓ vWF in Defect in platelet plug formation?
Defect in platelet to vWF adhesion
325
How is von Willebrand disease consider?
Mild but most common inherited bleeding disorder
326
Inheritance mode of von Willebrand disease
Autosomal dominant
327
How is von Willebrand disease diagnose?
In most cases by ristocetin cofactor assay (↓ agglutination is diagnositic)
328
Treatment for von Willebrand disease
DDAVP (Desmopressin), which releases vWF stored in endothelium
329
Mixed platelet and coagulation disorders
von Willebrand disease
| DIC
330
Labs found in Disseminated intravascular coagulation
↓ Platelet Count
↑ Bleeding time
↑ PT
↓ PTT
331
Pathophysiology of Disseminated intravascular coagulation (DIC)
Widespread activation of clotting lead to a deficiency in clotting factors, which creates a bleeding state
332
Causes of DIC
```
STOP Making New Thrombi
Sepsis
Trauma
Obstetric complications
acute Pancreatitis
Malignancy
Nephrotic syndrome
Transfussion
```
333
Findings of Disseminated intravascular coagulation
Schistocytes, ↑ fibrin split products (D- dimers), ↓ fibrinogen, ↓ Factor V and VIII
334
Hereditary thrombosis syndromes leading to hypercoagulability
Factor V Leiden
Prothrombin gene mutation
Antitbrombin deficiency
Protein C or S deficiency
335
Most common cause of inherited hypercoagulability in whites
Factor V Leiden
336
What is the Factor V Leiden?
Production of mutant factor V that is resistant to degradation by activated protein C
337
Pathophysiology of Prothrombin gene mutation
Mutation in 3' untranslated region→ ↑ production of prothrombin ↑ plasma levels and venous clots
338
How is Antithrombin deficiency gotten?
Inherited deficicency of antithrombin
| And Acquired
339
What effect does antithrombin deficiency has on PT, PTT, or thrombin time?
Has no direct effect on them
340
Hois PTT affected by Antithrombin deficiency?
No direct effect on it, but diminishes the increase in PTT following heparin administration
341
How can antithrombin deficiency be acquired?
Renal failure/ nephrotic syndrome → antithrombin loss in urine → ↑ factors II and X
342
What is the result of Protein C or S deficiency?
↓ ability to inactivate factors V and VIII
343
What risk is increased with Protein C or S deficiency?`
For Thrombotic skin necrosis with hemorrhage following administration of warfarin
344
Components of Blood transfusion therapy
Packed RBCs
Platelets
Fresh frozen plasma
Cryoprecipitate
345
What is the dosage effect of Packed RBCs?
↑ Hb and O2 carrying capacity
346
Clinical use for Packed RBCs
Acute blood loss, severe anemia
347
Dosage effect of Platelets
↑ Platelet count (↑ 5000/mm3/ unit)
348
Which is the clinical use for Platelets as blood transfusion therapy?
Stop significant bleeding (thrombocytopenia, qualitive platelet defects)
349
What is the purpose to administer fresh frozen plasma?
↑ coagulation factor levels
350
Clinical use for Fresh frozen plasma
DIC, cirrhosis, warfarin overdose, exchange transfusion in TTP/HUS
351
Contains fibrinogen, factor VIII, factor XIII, vWF, and fibronectin
Cryoprecipitate
352
Clinical use for Cryoprecipitate
Treat coagulation factor deficiencies involving fibrinogen and factor VIII
353
What is the dosage effect of Cryoprecipitate?
Contains fibrinogen, factor VIII, factor XIII, vWF, and fibronectin
354
Which are the blood transfussion risks?
Infection transmission (low)
Transfusion reactions
Iron overload
Hypocalcemia (citrate is a calcium chelator)
Hyperkalemia (RBCs may lyse in blood units)
355
What is Leukemia?
Lymphoid or myeloid neoplasms with widespread involvement of bone marrow
356
Where are tumor cells ussually found in Leukemia?
In peripheral blood
357
What is Lymphoma?
Discrete tumor masses arising from lymph nodes
358
How is lymphoma often presented?
Blur definitions
359
What is leukemoid reaction?
Acute inflammatory response to infection
360
Labs in Leukemoid reaction
↑ WBC count with ↑ neutrophils and neutrophil precursors such as band cells (left shift)
↑ Leukocyte ALP
361
Contrast of Leukemoid reaction with CML
Both have ↑ WBC count with left shift, but ↓ Leukocyte ALP
362
Characteristics of Hodgkin lymphoma
Localized, single group of nodes; extranodal rarecontigous spread
363
Which is the stronger predictor of prognosis in Hodgkin lymphoma?
Contigous spread
364
Who has better prognosis between non Hodgkin and Hodgkin lymphoma?
Hogdkin lymphoma has better prognosis
365
Which cells are characteristic of Hodgkin lymphoma?
Reed Sternberg cells
366
Groups of age that present more Hodgkin lymphoma?
Bimodal distribution- young adulthood and > 55 years
367
Which sex is at higher risk of Hodgkin lymphoma?
More common in men except Nodular sclerosing type
368
What factor is associated to Hodgkin lymphoma?
50 % of cases associated with EBV
369
Clinical findings of Hodgkin lymphoma
Constitutional ("B") signs/ symptoms -low- grade fever, night sweats, weight loss
370
Characteristics of Non Hodgkin lymphoma
Multiple, peripheral nodes; extranodal involvement common; non contigous spread
371
Which cells are characterisitic of Non Hodgkin lymphoma?
Majority involve B cells (except those of lymphoblastic T cell origin)
372
Group of age for Non Hodgkin lymphoma
Peak incidence for certain subtypes at 20-40 years old
373
Factors associated to Non Hodgkin lymphoma
May be associated with HIV and immunosuppresion
374
Clinical findings of Non Hodgkin lymphoma
Fewer constitutional sign/ symptoms
375
What are the Reed-Sternberg cells?
Distinctictive tumor giant cell seen in Hodgkin disease
376
Characteristics of Reed-Sternberg cells
Binucleate or bilobed with the 2 halves as mirror images ("owl eyes")
377
Which CD do Reed Sternberg cells have?
CD15
| CD30
378
Cell origin of Reed-Sternberg cells
B cell
379
Are Reed-Sternberg cells necessary for diagnosing Hodgkin disease?
Necessary but not sufficient for a diagnosis of Hodgkin disese
380
Which microscopic characteristics have better prognosis for Hodgkin disease?
Strong stromal or lymphocytic reaction against RS cells
381
Most common form of Hodgkin lymphoma
Nodular sclerosing
382
Which sex group is more affected by Nodular Sclerosing Hodgkin lymphoma?
Women and men equally
383
Which type of Hodgkin lymphoma has better prognosis?
Lymphocyte rich form
384
Which types of Hodgkin lymphoma have poor prognosis?
Lymphocyte mixed or depleted forms have poor prognosis
385
How are Non Hodgkin lymphoma classified?
Neoplasm of Mature B cells
| Neoplasm of mature T cells
386
Non Hodgkin lymphoma of mature B cells
Burkitt lymphoma
Diffuse large B cell lymphoma
Mantle cell lymphoma
Follicular lymphoma
387
In whom is more common Burkitt lymphoma?
Adolescents or young adults
388
Which gene is affected in Burkitt lymphoma?
t (8; 14)- translocation of c-myc (8) and heavy chain Ig (14)
389
Microscope characteristics of Burkitt lymphoma
"Starry sky" apperacne, sheets of lymphocytes with interpersed macrophages
390
What is associted to Burkitt lymphoma?
EBV
391
Clinical manifestations of Burkitt lymphoma
Jaw lession in endemic form in Africa
| Pelvis or abdomen in sporadic form
392
Usual group of age of presentation of Diffuse large B cell lymphoma
Usually Older adults, but 20% in children
393
Gen affected in Diffuse large B cell lymphoma
t (14:18)
394
Most common type of non Hodgkin lymphoma in adults
Diffuse large B cell lymphoma
395
Who are more affected by Mantle cell lymphoma?
Older males
396
Gen affected in Mantle cell lymphoma
t (11; 14)- translocation of cyclin D1 (11) and heavy chain Ig (14)
397
CD found in Mantle cell lymphoma
CD5+
398
Who are at higher risk for Follicular lymphoma?
Adults
399
Gen affected in Follicular lymphoma?
t (14; 18)- translocation of heavy chain Ig (14) and bcl-2
400
How is the course of Follicular lymphom?
indolent
401
What is the effect of bcl2?
Inhibits apoptosis
402
How is Follicular lymphom presentation?
With painless "waxing and waning" lymphadenopathy
403
Non Hodgkin Lymphoma of mature T cells
Adult T cell lymphoma
| Mycosis fungoides
404
In which patients os more often seen Adult T cell lymphoma?
Adults
405
What causes Adult T cell lymphoma? with what is associated?
By HTLV-1
| associated with IV drgu abuse
406
Who are mainly affected by Adult T cell lymphoma?
Populations of Japan, West Africa, and the Caribean
407
How is Adult T cell lymphoma manifested?
Adult present with cutaneois lesions
408
How are bones affected by Adult T cell lymphoma?
Lytic bone lesions, hypercalcemia
409
How else is Mycosis Fungoide known?
Sézary syndrorme
410
Group of age affected by Mycosis Fungoide
Adults
411
How is Mycosis Fungoide presented?
Adults present with cutaneous patches plaques/ tumors with potential to spread to lymph nodes and viscera
412
What is seen in Sézary syndrome?
Circulating malignant cells seen in Sézary syndrome
413
How is the course of Sézary syndrome?
Indolent
414
What CD is seen in Mycosis Fungoides?
CD4+
415
Origin Cells from Multiple Myeloma
Monoclonal plasma cell
416
What apperance do monoclonal plasma cell have?
"fried egg" apperance
417
From where does Multiple Myeloma arise?
In the marrow
418
What does Multiple Myeloma produce?
Large amounts of IgG (55%) or IgA (25%)
419
Most common primary tumor arising within bone in the eldery
Multiple myeloma
420
Main Group of age affected by Multiple myeloma
>40-50 years old
421
Which factors are associated to Multiple myeloma?
```
↑ susceptibility to infection
Primary amyloidosis (AL)
```
422
What is seen in imaging studies in Multiple myeloma?
Punched out lytic bone lesions on x ray
423
What in seen in serum protein electrophoresis in Multiple Myeloma?
M spike
424
What is seen in urine in Multiple Myeloma?
Ig light chains in urine (Bence Jones protein)
425
Protein found as Ig light chains in urine
Bence Jones protein
426
What is seen in smear in Multiple Myeloma?
Rouleaux formation
427
What is Rouleaux formation?
RBCs staked like poker chips in blood smear
428
Characteristics of plasma cells seen in Multiple Myeloma
Numerous plasma cells with "clock face" chromatin and intracytoplasmic inclusions containing immunoglobulin
429
What difference does Multiple Myeloma has with Waldenstrom macroglobulinemia?
M spike= IgM (→ hyperviscocity symptoms)
| No lytic bone lesions
430
With which disease is Monoclonal gammopathy of undetermined significance related to?
Asymmptomatic precursor to Multiple myeloma
431
What is Monoclonal gammopathy of undetermined significance?
Monoclonal expansion of plasma cells with serum monoclonal protein
432
How much patients with Monoclonal gammopathy of undetermined significance develop Multiple Myeloma?
1-2% per year
433
Findings of Multiple myeloma
```
CRAB
hyperCalcemia
Renal insufficiency
Anemia
Bone lytic lesions/ Back pain
```
434
What are Myelodysplastic syndromes?
Stem cell disorders involving inneffective hematopoiesis → defects in cell maturation of all non lymphoid lineages
435
What causes Myelodysplastic syndromes?
Caused by de novo mutations or environmental exposure
436
Which environmental exposure cause Myelodysplastic syndromes?
Radiation, Benzene, chemotherapy
437
What risk do Myelodysplastic syndromes have?
Risk of transformation to AML
438
What is Pseudo Pelger Huet anomaly?
Neutrophils with bilobed nuclei (two nuclear masses connected with a thin filament of chromatin) typically seen after chemotherapy
439
Pseudo Pelger Huet anomaly is associated to this disease
Myelodysplastic syndrome
440
Pathophysiology of Leukemias
Unregulated growth of leukocytes in bone marrow → ↑ or ↓ number of circulating leukocytes in blood and marrow failure
441
What is the result of Leukemias?
Anemia (↓ RBCs), infections (↓ mature WBCs) and hemorrhage (↓ platelets)
442
Which structures could be infiltrated by Leukemic cells?
Liver, Spleen and lymph nodes
443
Types of Leukemias
Lymphoid neoplasms
| Myeloid neoplasms
444
Who are lymphoid neoplasms?
Acute lymphoblastic leukemia/ lymphoma (ALL)
Small lymphocytic lymphoma (SLL)/ Chronic lymphocytic leukemia (CLL)
Hairy Cell leukemia
445
At which age does Acute Lymphoblastic leukemia commonly appears?
446
How is T cell ALL presented?
Mediastinal mass (leukemic infiltration of the thymus)
447
Which disease is associated to ALL?
Down syndrome
448
Findings of ALL
Peripheral bloof and bone marrow have ↑↑↑ lymphoblasts
449
Special biomarkers for ALL
TdT+
| CD10+
450
What is the use for TdT+?
Marker of pre-T and pre-B cells
451
What does CD10 identifies?
pre-B cells only
452
Which Lymphoid neoplasm is the most responsive to therapy?
Acute lymphoblastic leukemia/ lymphoma (ALL)
453
Acute lymphoblastic leukemia/ lymphoma (ALL) may spread to...
CNS and testes
454
Mutations presented in Acute lymphoblastic leukemia/ lymphoma (ALL)
t (12; 21)
455
Prognosis of t (12;21) mutation
Better prognosis
456
How else is Chronic lymphocytic leukemia known?
Small lymphocytic lymphoma (SLL)
457
At what age does CLL commonly appears?
> 60 years
458
What CD are seen in CLL?
CD20+, CD5+ B cell neoplasm
459
How is the progression of SLL?
Progresses Slowly
460
Symptoms of SLL
Often asymptomatic
461
What is seen in peripheral blood smear in CLL?
Smudge cells
462
What else is found in CLL?
Hemolytic anemia
463
What is the difference between CLL and SLL?
SLL same as CLL except CLL has increasedperipheral blood lymphocytosis or bone marrow involvement
464
Who are at higher risk for Hairy cell leukemia?
Adults
465
How is Hairy cell leukemia consider?
Mature B cell tumor in the elderly
466
Characteristic of cells in Hairy cell leukemia?
Cells have filamentous, hairy like projections
467
Which stain is positive in Hairy cell leukemia ?
TRAP (tartrate resistant acid phosphate)
468
By which method is TRAP replaced inthe study of Hairy cell leukemia?
With flow cytometry
469
What do Hairy cell leukemia causes?
Marrow fibrosis→ dry tap on aspiration
470
Treatment for Hairy cell leukemia
Cladribine (2-CDA), an adenosine analog (inhibits adenosine deaminase)
471
Who are Myeloid neoplasms?
Acute myelogenous leukemia (AML)
| Chronic Myelogenous leukemia (CML)
472
Age of onset of Acute myelogenous leukemia?
Median onset 65 year
473
In which disease are Auer rods seen?
Acute myelogenous leukemia
474
What are Auer rods?
Peroxidase + cytoplasmic inclusions seen mostly in M3 AML
475
What is seen in blood smear in Acute myelogenous leukemia?
↑↑↑ circulating myeloblasts on peripheral smear
476
Risk factor for Acute myelogenous leukemia
Prior exposure to alkylating chemotherapy, radiation, myeloproliferative disordes, Down syndrome
477
Type of mutation seen in Acute myelogenous leukemia
t(15; 17)→ M3 AML subtype
478
M3 AML subtype responds to...
responds to all-trans retinoic acid (vitamin A)
479
What do trans retinoic acid (vitamin A) causes in M3 AML subtype?
Inducing differentiation of myeloblasts
480
What pathology could be present in M3 AML subtype?
DIC
481
What induces DIC in M3 AML subtype?
Chemotherapy due to release of Auer rods
482
Peak incidence of Chronic Myelogenous leukemia (CML)
45-85 years
483
Median age of diagnosing Chronic Myelogenous leukemia (CML)
64 years
484
Which chromosome is related to Chronic Myelogenous leukemia (CML)?
Philadelphia chromosome
485
Philadelphia chromosome
t (9;22), bcr-abl
486
What does Philadelphia chromosome define?
Myeloid stem cell proliferation
487
How is Chronic Myelogenous leukemia (CML) presented?
↑ neutrophils, metamylocytes, basophils
488
Clinical finging of Chronic Myelogenous leukemia (CML)
Splenomegaly
489
What could be the probable evolution of Chronic Myelogenous leukemia (CML) ?
May accelerate and transform to AML or ALL ("blast crisis")
490
What is a blast crisis?
When Chronic Myelogenous leukemia transforms to AML or ALL
491
Other characteristic of Chronic Myelogenous Leukemia
Very low leukocyte alkaline phosphatase (LAP) as a result of low activity in mature granulocytes
492
What difference does Chronic myelogenous leukemia has with Leukomoid reaction
CML has ↓ Leukocyte Alkaline phosphatase
| Leukemoid reaction presents with ↑ Leukocyte Alkaline phosphatase
493
Which is the treatment for Chronic myelogenous leukemia?
Responds to imatinib
494
What is imatinib?
A small molecule inhibitor of the bcr-abl tyrosine kynase
495
Which translocation is Philadelphia chromosome?
t (9; 22)
496
Associated disorder to Philadelphia chromosome
CML (bcr-abl hybrid)
497
Pathology associated to t(8:14)
Burkitt lymphoma
498
What is activated in Burkitt lymphoma?
c-myc activation
499
Translocation of Mantle cell lymphoma
t (11:14)
500
Associated disorder to cyclin D1 activation
Mantle cell lymphoma
501
Disorder associated to t(14; 18)
Follicular lymphomas
502
What is activated in Follucular lymphomas?
bcl-2 activation
503
Pathology associated to t(15; 17)
M3 type pf AML (responsive to all trnas retinoic acid)
504
Proliferative disorders of dendritic cells from nonocyte lineage
Langerhans cell histiocytosis
505
Alternative name for dendritic cells
Langerhans cell
506
How is Langerhans cell histiocytosis presented?
Presents in child as lytic bone lesions and skin rash or as recurrent otitis media with mass involving the mastoid bone
507
What is the problem with dendritic cells in Langerhans cell histiocytosis?
Cells are functionally immature and do not efficiently stimulate primary T lymphocytes via antigen presentation
508
What is expressed by cells in Langerhans cell histiocytosis?
S-100 (mesodermal origin) and CD1a
509
Histologic characteristic of Langerhans cell histiocytosis
Birbeck granules ("tennis rackets")
510
Chronic myeloproliferative disorders
Polycythemia vera
Essential thrombocytosis
Myelofibrosis
CML
511
Non-receptor tyrosine kinase mutated in Chronic myeloproliferative disorders
JAK2
512
What is the function of JAK2?
Is involved in hematopoietic growth factor signaling
513
Which myeloproliferative disorder in not implicated in mutations of JAK2?
CML
514
Main characteristics of Polycythemia vera
Hematocrit > 55%, somatic (non heraditary) mutation in JAK2 gene
515
How is Polycythemia often presented?
As intense itching after hot shower
516
Rare but classic symptom of Polycythemia vera
Erythromegalia
517
What is Erythromegalia?
Severe, burning pain and reddish or bluish coloration
518
What causes Erythromegalia in Polycythemia vera?
Episodic blood clots in vessels of the extremities
519
What induces a secondary polycythemia?
Via natural or artificial ↑ in EPO levels
520
Which pathology is similar to Essential thrombocytosis?
Polycythemia vera
521
What is the main problem of Essential thrombocytosis?
Specific for overproduction of abnormal platelets
522
What is the result of Overproduction pf abnormal platelets?
Bleeding, thrombosis
523
What does Bone marrow contains in Essential thrombocytosis?
Enlarged megakaryocytes
524
Main characteristic of Myelofibrosis
Fibrotic obliteration of bone marrow
525
Cell characteristics on Myelofibrosis
Teardrop RBCs and immature forms of the myeloid line
526
In this chronic myeloproliferative disorder we see bcr-abl transformation
CML
527
What does bcr-abl transformation leads to in CML?
↑ cell division and inhibition of apoptosis
528
Imatinib is the drug of choice in this myeloproliferative disorder
CML
529
Comercial name for Imantinib
Gleevec
530
In blood counts how are cell affected in Polycythemia vera?
↑ RBCs
↑ WBCs
↑ Platelets
531
What mutation is seen in Polycythemia vera?
JAK2
532
What cells are affected in Essential thrombocytosis?
↑ Platelets
533
Is JAK2 mutated in Essential thrombocytosis?
Yes, in 30-50%
534
How are blood counts in Myelofibrosis?
↓ RBCs
| Variable WBCs and Platelets
535
Is JAK2 mutated in Myelofibrosis?
Yes, in 30-50%
536
How are blood count in CML?
↓ RBCs
↑ WBCs
↑ Platelets
537
Is JAK2 mutated in CML?
No
538
Which gene is mutated in CML?
Philadelphia chromosome
539
Types of Polycythemias
Relative
Appropriate absolute
Inappropriate absolute
Polycythemia vera
540
In relative polycythemia what is the problem?
↓ plasma volume
541
What leads to relative polycythemia?
↓ plasma volume (dehydration, burns)
542
What is the result of appropriate absolute polycythemia?
↑ RBC mass
| ↑ EPO levels
543
What is the main cause of appropriate absolute polycythemia?
↓ O2 saturation
544
What pathologies are associated to appropriate absolute polycythemia?
Lung disease, congenital heart disease, high altitude
545
What is seen in inappropriate absolute polycythemia?
↑ RBC mass
| ↑ EPO levels
546
Main causes of inappropriate absolute polycythemia
```
Renal Carcinoma
Wilms tumor
Cyst
Hepatocellular carcinoam
Hydronephrosis
```
547
Main cause of inappropriate absolute polycythemia
Due to ectopic EPO
548
What are the alterations seen in Polycythemia vera?
↑ Plasma volume
↑↑ RBC mass
↓ EPO levels
549
Why is EPO decreased in Polycythemia vera?
Due to negative feedback
