Anemias Flashcards
1
Q
Macrocytic anemia is divided to
A
- Megaloblastic
2. Non-megaloblastic
2
Q
Megaloblastic macrocytic anemias - types
A
- B12 deficiency
- Folate deficiency
- Orotic aciduria
3
Q
Non-Megaloblastic macrocytic anemias
A
- Hypothyroidism
- Liver disease
- Alcoholism
- Reticulocytosis
- Diamond-Blackdan anemia
4
Q
Normocytic anemia is divided to
A
- Nonhemolytic (reticulocytes normal or decreased)
2. Hemolytic (reticulocyte increased)
5
Q
Nonhemolytic normocytic anemias
A
- Anemia of chronic disease (early)
- Iron deficiency (early)
- Chronic kidney disease
- Aplastic anemia
6
Q
Hemolytic normocytic anemias are divided to
A
- Intrinsic
2. Extrinsic
7
Q
Extrinsic Hemolytic normocytic anemias
A
- Autoimmune
- Macroangiopathic
- Microangiopathic
- Infections
8
Q
Intrinsic Hemolytic normocytic anemias
A
- RBC membrane defects (hereditary spherocytosis)
- RBC enzymes deficiency (G6PD, pyruvate kinase)
- HBC defects
- Paroxysmal nocturnal hemlglobinuria
- Sickle cell anemia
9
Q
Causes of iron deficiency
A
Chronic bleeding (gi, menorrhagia)
Malnutrition
Malabsorption
Increased demand (pregnancy)
10
Q
Iron deficiency iron labs
A
- Decreased iron
- Decreased ferritin
- Increase TIBC
- microcytosis and hypochromasia (central pallor)
11
Q
Iron deficiency symptoms
A
- Fatigue
- Conjunctival pallor
- Spoon nails (koilonychia)
- Macrocytosis and hypochromia
- pica (consumption of nonfood substance)
- Plummer-Vinson syndrome
12
Q
Plummer-Vinson triad
A
- Iron deficiency anemia
- Esophageal web
- dysphagia
(also atrophic glossitis)
13
Q
a Thalassemia: cis vs trans thalassemia
A
Cis: Asia, -/- a/a (same chromosome)
Trans: Africa, a/- a/- (separate chormosomes)
14
Q
4 allele a deltion
A
Hb bart (4γ) Hydrops fetalis
15
Q
3 allele a deletion
A
very little α
HbH (4β)
16
Q
β-thalassemia mechanism
A
Point mutation in splice sites and promoters–> decreased β-globin synthesis
17
Q
Β thalassemia minor (heterozygotes) - definition/ mechanism/presentation/diagnosis
A
heterozygote –> β chain is underproduced –> usually asymptomatic
HbA2>3,5% on electrophoresis
18
Q
Major β-thalassemia major - presentation (besides anemia) and mechanism (when starts)
A
- marrow expansion –> skeleta deformities (Crew cut on skull x ray) + chipmunk facies
- extramedullary hematopoiesis –> hepatosplenomegaly
Until 6 months is asymptomatic (HbF)
19
Q
Major β-thalassemia major - definition/lab/treatment
A
homozygote –> β chain is absent
severe microcytic, hypochromic anemia with target cells and increased anisopoikilocytosis, high HbF
treatment: blood transfusion (2ry hemochromatosis)
20
Q
HbS/β-thalassemia heterozygote
A
Mild to moderate sickle cell anemia depending on amount of β-globin production
21
Q
Microcytic anemias
A
- Iron deficiency (late)
- Thalassemias
- Anemia of chronic disease (late)
- Lead poisoning
- Sideroblastic anemia
22
Q
Lead inhibits (causing)
A
Ferrochelatase and ALA dehydratase –> decreases heme and increase protoporphyrin
rRNA degradation –> rRNA aggregation –> basophilic stippling
23
Q
Lead poisoning symptoms and signs
A
- Burton lines
- Metaphysis lines on x ray
- Encephalopathy
- Erythrocyte basophilic stippling
- Siderblastic anemia
- ABDOMINAL COLIC
- Drops of wrist and foot
- KIDNEY DISEASE
24
Q
Used for lead chelation in kids
A
Succimer
25
Lead poisoning-first line treatment
Dimercaprol, EDTA
26
Sideroblastic anemia types of causes (and causes)
1. Genetic --> X-linked defect in δ-ALA synthase gene
2. acquired --> Myelodysplastic syndrome
3. reversible --> Alcohol (MC), Lead, Vit B6 deficiency, Isoniazid, Copper deficiency
27
Genetic causes of sideroblastic anemia
X-linked defect in δ-ALA synthase gene
28
Causes of acquired sideroblastic anemia
Myelodysplastic syndrome
29
Causes of reversible sideroblastic anemia
1. Alcohol (MC)
2. Lead
3. Vit B6 deficiency
4. Isoniazid
5. Copper deficiency
30
sideroblastic anemia - labs
- Prussian blue-stained mitochondria (iron) seen in bone morrow (Ringed sideroblasts)
- basophilic stippling of RBCs in peripheral smear
- increased iron, normal/low TIBC, increased ferritin
31
Findings of megaloblastic anemia
mechanism: impaired DNA synthesis --> maturation of nucleus of precursor cells in bone marrow delayed relative to maturation of cytoplasm
findings: 1. RBC macrocytosis 2. Hypersegmented neutrophils 3. Glossitis
32
Causes of folate defciency
1. Malnutrition (alcohol)
2. Malabsorption
3. Drugs (trimethoprim, phenytoin, methotrexate)
4. Requirement (hemolytic anemia, pregnancy)
33
Causes of B12 (cobolamin) deficiency
1. Insufficient intake (veganism)
2. Malabsorption (crohn)
3. Pernicious anemia
4. Diphyllobothrium latum
5. Gastrectomy
34
Folate deficiency vs b12 deficiency according to methylmalonic acid, homocystein, and neurologic symptoms
1. Methylmalonic acid (increased only in B12)
2. Neurologic symptoms (only in B12)
3. Homocysteine (increased in Both)
35
Neurologic symptoms of B12 deficiency (and why)
Sabacute combined degeneration due to its involvement in fatty acid pathays and myelin synthesis:
1. Spinocerebellar tract
2. Lateral corticospinal tract
3. Dorsal column dysfunction
36
Orotic aciduria pathophysiology
Defect in UMP synthesis (orotic acid to UMP, de novo pyrimidine synthesis pathway)
AR
37
Orotic aciduria symptoms
1. Failure to thrive
2. Developmental delay
3. Megaloblastic anemia refractory to folate and B12
(NO HYPERAMMONIA)
38
Orotic aciduria treatment/diagnosis
UMP (to bypass)
| diagnosis: Orotic acid in urine
39
Orotic aciduria vs ornithine trancarbamylase
Orotic aciduria has no hyperammonemia
40
Anemia of chronic disease pathophysiology
Inflammation--> increases hepsidin --> binds ferroportin (on intestinal mucosal and macrophages) inhibiting iron trnasport--> decreases the releasing of iron from macrophages and decrease absorption
41
Anemia of chronic disease - associated conditions/treatment
1. RA 2. SLE 3. Neoplasia 4. Chronic kidney disease
treatment: EPO in chronic kidney
42
Anemia of chronic disease iron status / type of anemia
Decreased iron
Decreased TIBC
Increased ferritin
--> Normocytic, but can become microcytic
43
Aplastic anemia is caused by
Failure or destruction of myeloid stem cells
44
Causes of aplastic anemia
1. Radiation 2. Drugs (benzene, chloramphenicol, alkylating agents) 3. Viral agents (parvovirus B19, EBV, HIV, HCV)
4. Fanconi anemia (DNA repair defect) 5. Idiopathic (immune mediate, 1ry stem cell defect)-may follow acute hepatitis
45
Aplastic anemia-bone marrow appearance
```
Hypocellular
Fatty infiltration (Dry bone marrow tap)
```
46
Aplastic anemia symptoms and findings
Fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infections
Pancytopenia (severe anemia, leukopenia, thrombocytopenia) --> but normal cell morphology
47
Aplastic anemia treatment
1. Withdrawal of offending agent
2. Immunosuppressive regimens (antithymocyte globulin, cyclosporine)
3. Bone marrow allograft
4. RBC/platelets transfusion
5. Bone marrow stimulation (eg. GM-CSF)
48
Hereditary spherocytosis - due to defect in
proteins interacting iwth RBC membrane skeleton and plasma membrane
1. Ankyrin
2. Band 3
3. Protein 4.2
4. Spectrin
49
Hereditary spherocytosis labs
1. Osmotic fragility test (+)
2. Normal to decreased MCV with abudance of cells
3. Increased RDW
4. Increased MCHC (no central pallor)
5. round RBCs with less surface area
50
Hereditary spherocytosis treatment/intravascular vs extravascular/susceptible for
- Splenectomy (causes splenomegaly)
- extravascular hemolysis
- susceptible for B19
51
Most common enzymatic deficiency of RBCs
G6PD
| XR
52
G6PD location of hemolysis / mechanism
Intravascular AND extravascular
| defect in G6PD --> low glutathione --> high RBCs susceptibility to oxidant stress
53
G6PD deficiency - hemolytic anemia following
1. Sulfa drugs
2. Antimalarias
3. Infections
4. Fava beans
54
G6PD deficiency symptoms, beside anemia
BACK PAIN
| HEMOGLOBINURIA (few days after oxidant stress)
55
Pyruvate deficiency anemia - presentation
Hemolytic anemia in a newborn
56
Pyruvate deficiency anemia pathophysiology
AR. Decreased ATP--> rigid RBCs --> extravascular hemolysis
57
HBC pathophysiology
Lysine instead of glutamic acid in β globin
58
Starting event of paroxysmal nocturnal hemoglobinuria / mechanism
Acquired mutation in hematopoietic stem cell --> impaired synsthesis of for GPI anchor for decay-accelerating factor that protects RBCs from complement --> increased C-mediated intravascular RBCs lysis
59
paroxysmal nocturnal hemoglobinuria increases the incidence of
ACUTE LEUKEMIAS
60
paroxysmal nocturnal hemoglobinuria triad
1. Coombs hemolytic anemia
2. Pancytopenia
3. Venous thrombosis
61
paroxysmal nocturnal hemoglobinuria flow cytometry
CD 55/59 ( - )RBCs
62
paroxysmal nocturnal hemoglobinuria treatment
Eculizumab (terminal complement inhibitor)
63
Sickle cell anemia mutation / intravascular vs extravascular hemolysis
Valine instead of Glutamic acid
| intravascular + extravascular
64
Sickle cell x ray
Crew cut on skull (marrow expansion)
65
Sickle cell complications
1. Aplastic crisis (parvovirus B19)
2. Autosplenectomy (howell-jolly bodies)
3. Splenic infract/sequestration
4. Salmonella osteomyelitis
5. Renal papillary necrosis (low PO2 in papilla) --> microhematuria (medullary infracts)
6. Painful crisis (vaso-occlusive): dactylitis (painful swelling of hands/feets), acute chest syndrome, avascular necrosis, stroke. priapism
66
Sickle cell anemia diagnosis and treatment
Diagnosis: Hb electrophoresis
Treatment: hydroxyurea, hydration
67
Hemolytic anemia-infections (mechanism)
Malaria and Babesia
| increased destruction of RBCs
68
Causes of Macroangiopathic anemia
Prosthetic heart valce and Aortic stenosis --> mechanical destruction
69
Causes of microangiopathic anemia
DIC, SLE, MALIGNANT HYPERTENSION, TTP/HUS
70
Pregnancy (ocp use) - iron status
Increases the Transferin/TIBC
| Decrease the transferin saturation
71
Autoimmune hemolytic anemia types
Warm (IgG)
| Cold (IgM and complement)
72
Causes of Warm agglutinin
1. SLE
2. CLL
3. Drugs (methyldopa)
4. Idiopathic
- -> chronic anemia
73
Causes of Cold agglutinin
1. CLL
2. Mycoplasma pneumonia
3. Infectious mononucleosis
4. Idiopathic
- -> acute anemia
74
Megaloblastic anemia mechanism
Impaired DNA synthesis --> maturation of nucleus of precursor cells i. Bone marrow delayed relative to maturation in cytoplasm
75
B12 deficiency --> mechanism of neurological symptoms
Involvement of B12 in fatty acid pathway and myelin synthesis
76
thalassemia-a - 2 allele vs 1 allele deletion
2 --> less clinically severe anemia
| 1 --> no anemia (clinically silent)
77
β-thalassemia - prevalent in
Mediterranean populations
78
risk of Lead exposure is increased in
old houses with chipped paint
79
sideroblastic anemia - treatment
B6, cofactor for δ-ALA synthase
80
how to predict simple the type of anemia (macro vs micro vs normocytic)
on peripheral blood smear, a lymphocyte nucleus is approximately the same size as a normocytic RBC:
if RBC larger than lymphocyte nucleus, consider macrocytosis. If smaller, microcytosis
81
B12 deficiency - historically is diagnosed with (explain)
Schilling test, a 4-stage test that determines if the cause is dietary insufficiency vs malabsorption
(WITH RADIOLABELED B12)
82
Non-Megaloblastic macrocytic anemias - mechanism / neutrophils
- DNA synthesis is unimpaired
| - not hypersegmented
83
Diamond-Blackfan anemia - description
Rapid-onset anemia within 1st year of life due to intrinsic defect in erythroid progenitor cells
84
Diamond-Blackfan anemia - lab
increased % of HbF (but low total Hb)
85
Diamond-Blackfan anemia - presentation
1. short stature
2. craniofacial abnormalities
3. upper extremity malformations (triphalangeal thumbs) in up to 50% of cases
86
drugs that causes aplastic anemia
1. benzene
2. chloramphenicol
3. alkylating agents
87
aplastic anemia - EPO?
increased
88
HbSC - presentation
milder thatn HbSS patients
89
HbC - homozygotes - blood smear
hemoglobin crystals within RBCs and target cells
90
Heterozygoges of SC anemia - advantage
resistance to malaria
91
prevelance of sickle cell in African american
8% carry an HbS allele
92
RBC agglutination with cold exposure - presentation
acute anemia
| painful, blue fingers and toes with cold exposure
93
Autoimmune anemia are usually Coombs ..?
positive
94
Direct Coombs test - mechanism
anti-Ig antibody (Coombs reagent added to patient's blood --> RBCs agglutinate if are coated with Ig
95
Indirect Coombs test - mechanism
normal RBCs added to patient serum --> if serum has anti RBC surface Ig, RBCs agglutinate whtn Coombs reagent added
96
The hemolytic anemias are divided according to
1. the cause of hemolysis (intrinsic vs extrinsic to the RBC)
2. the location of the hemolysis (intra vs extravascular)
97
extravascular hemolytic anemia - findings
1. Spherocytes in peripheral smear
2. high LDH
3. no hemoglobinuria/hemosiderinuria
4. increased UCB (--> jaundice)
5. urobilinogen in urine
98
intravascular hemolytic anemia - findings
1. low haptoglobin
2. high LDH
3. schistocytes
4. high reticulocytes
5. hemoglobinuria
6. hemosiderinuria
7. urobilinogen in urine
8. increased UCB
99
Fanconi anemia - mechanism of action
DNA repair defect causing bone marrow failure
100
Fanconi anemia - presentation
1. Aplastic anemia
2. Increased incidence of tumor/leukemia
3. Cafe au lait spots
4. Thumb/radial defects
