3.2 Flashcards
1
Q
serves as a barrier
A
Lipid Bilayer
2
Q
the ability to repeatedly bend, stretch, distort and return to normal discoid shape.
A
Deformability
3
Q
Elasticity- interactions between Spectrin and junctional
complexes.
A
Pliancy
4
Q
concentration of Hemoglobin and
maintenance of proper cell volume.
A
Cytoplasmic Viscosity
5
Q
Perpendicular to cytoskeleton, prevents loss of membrane= decreased surface area-to-volume ratio of RBC (Names)
A
Vertical (Structural Integrity)
6
Q
Prevents membrane from fragmenting in response to mechanical stress. (Names)
A
Horizontal (Mechanical stability)
7
Q
What are the hereditary diseases that are defective in their membrane structures
A
H. Spherocytosis
H. Elliptocytosis
H. Ovalocytosis
8
Q
What are the hereditary diseases that are defective in their membrane transport proteins
A
H. hydrocytosis
H. xerocytosis
9
Q
Acquired RBC membrane abnormalities
A
A. stomattocytosis
Spur cell
Paroxysmal nocturnal hemoglobinuria
10
Q
In H. spherocytosis, what are the mutated gene
A
B- Spectrin
A-Spectrin
Band 3
Ankyrin
Protein 4.2
11
Q
What kind of trait is hereditary spherocytosis
A
75% Autosomal Dominant
12
Q
Defects/ Mutations in proteins that disrupt the vertical interactions between
transmembrane proteins and cytoskeleton.
A
Hereditary Spherocytosis
13
Q
RBCs lose unsupported lipid membranes and acquire a decreased surface area-to volume
ratio
A
SPHEROCYTES
14
Q
What happens if the RBC membranes have abnormal permeability to cations?
A
Increase in Viscosity and cellular dehydration
15
Q
No deformability of a normal discoid RBC.
A
HEREDITARY SPHEROCYTOSIS
16
Q
Asymptomatic, RBC loss is compensated.
A
MILD HS (20-30%):
17
Q
Normal Hgb, Slight Increase in Bilirubin, Increased reticulocytes, and
presence of few spherocytes in Peripheral Blood Smear
A
MILD HS (20-30%):
18
Q
Usually seen in pregnancy, Infectious Mononucleosis, or in aging
A
MILD HS (20-30%):
19
Q
Hgb >8g/dL, Serum Bilirubin >2mg/dL, Reticulocyte count >8%
A
MODERATE HS (60%):
20
Q
Spherocytes in PBS.
A
MODERATE HS (60%):
21
Q
Hgb 6-8g/dL, Serum Bilirubin 2-3mg/dL, Reticulocyte count >10%
A
MODERATE to SEVERE HS (5-10%):
22
Q
Hgb <6g/dL, Serum Bilirubin >3mg/dL, Reticulocyte count >10%
A
SEVERE HS (3-5%):
23
Q
Require regular transfusions
A
SEVERE HS (3-5%):
24
Q
Hallmark of HS
A
Spherocytes:
25
small, round, dense RBCs
filled with Hgb, no central pallor.
Microspherocytes:
26
RBC Morphology:
Mutated gene in B-spectrin
Acanthocytes
27
RBC Morphology:
Mutated gene in Band 3
Pincered or mushroom shaped cells
28
RBC Morphology:
Mutated gene in EPB4.2
Ovalostomatocytes
29
True or False
Spherocytes are specific for hereditary spherocytosis
FALSE
Spherocytes are NOT specific for HS.
30
- MCHC: > 36mg/dL (for moderate to severe)
- MCV: WIR to slightly below
HEREDITARY SPHEROCYTOSIS
31
Lab Findings in H. Spherocytosis:
Serum Haptoglobin
Increase or Decrease?
Decrease
32
Lab Findings in H. Spherocytosis:
Serum Indirect Bilirubin
Increase or Decrease?
Increase
33
Lab Findings in H. Spherocytosis:
Serum Lactate Dehydrogenase
Increase or Decrease?
Increase
34
In the Bone Marrow Exam of hereditary spherocytosis, what will you see? Is it required for diagnosis?
Erythroid Hyperplasia
No, not required for diagnosis
35
Demonstrates Increased RBC Fragility on RBCs
with decreased surface area-to-volume ratios.
OSMOTIC FRAGILITY TEST
36
In OSMOTIC FRAGILITY TEST, RBCs are subjected to increasing ________
solutions.
hypotonic
37
Shift to the ____, Increased Osmotic Fragility
LEFT
38
Shift to the _____, Decreased Osmotic Fragility
Right
39
In osmotic fragility test
Time-consuming, Needs Fresh _______
sample collected without ______, accurately
prepared _____ solutions.
Heparinized; Trauma; NaCl
40
Confirmatory test for HS. More sensitive alternative to EOFT
EOSIN-5’-MALEIMIDE BINDING TEST
41
Measures Mean Fluorescence Intensity.
EOSIN-5’-MALEIMIDE BINDING TEST
42
rare associated with viral syndromes i.e. Infectious Mononucleosis.
Spleen enlarges, sluggish blood flow and destroys RBCs.
HEMOLYTIC CRISIS
43
Marked decrease in reticulocytes. Associated with Parvovirus B19 infection,
destroys progenitor cells in BM and suppresses erythropoiesis.
APLASTIC CRISIS-
44
Increased Folate utilization. Particularly acute during pregnancy.
MEGALOBLASTIC CRISIS
45
Treatment for H. Spherocytosis
- Regular Transfusion
- Splenectomy
46
Differential Diagnosis in H. spherocytosis
- HS: Negative DAT (Direct Antiglobulin Test)
- EMA Binding Test
47
Treatment for H. Elliptocytosis
- Regular Transfusion
- Splenectomy
48
what trait is the hereditary elliptocytosis?
Autosomal dominant
49
Mutated gene in
a- Spectrin,
B-Spectrin,
Protein 4.1
What disease?
hereditary elliptocytosis
50
Weaken the Mechanical Stability of the
membrane
hereditary elliptocytosis
51
More common in Africa and Mediterranean
regions
hereditary elliptocytosis
52
Defects/ Mutations in proteins that disrupt the horizontal/ lateral interactions in
the protein cytoskeleton.
hereditary elliptocytosis
53
Normal, discoid RBCs become elliptical from repeated exposure to shear stress in
the peripheral circulation
ELLIPTOCYTES
54
ELLIPTOCYTOSIS IN PATIENTS WITH LEACH PHENOTYPE lacks what?
Lacks Gerbich Antigens and GPC
55
Mutations in Glycoprotein C what are the defect?
GPC and protein 4.1 interactions
56
Severe form of Hereditary Elliptocytosis
HEREDITARY PYROPOIKILOCYTOSIS
57
Decreased Thermal Stability. (Marked RBC fragmentation on heating).
HEREDITARY PYROPOIKILOCYTOSIS
58
Extreme Poikilocytosis with fragmentation, microspherocytosis and
elliptocytosis (similar to patients with thermal burns).
HEREDITARY PYROPOIKILOCYTOSIS
59
MCV is very low (50 to 65fL)
- Lower fluorescence in EMA binding test compared to HS.
HEREDITARY PYROPOIKILOCYTOSIS
60
Diseases that are less than 1/3 of the RBCs are elliptocytes (TIMPMM)
(IDA,Thalassemia,megaloblastic anemia, MDS,Primary Myelofibrosis
61
Cholelithiasis can develop.
HEREDITARY ELLIPTOCYTOSIS and spherocytosis
62
Southeast Asian Ovalocytosis (SAO)
HEREDITARY OVALOCYTOSIS
63
WHat trait is HEREDITARY OVALOCYTOSIS?
Mainly Autosomal Dominant
64
WHat mutated gene has HEREDITARY OVALOCYTOSIS
Band 3
65
True or False
HEREDITARY OVALOCYTOSIS decreases in membrane rigidity?
False; Increases
66
More common in the malaria belt of
Southeast Asia
HEREDITARY OVALOCYTOSIS
67
Results from only one mutation, deletion of 27 base pairs in the gene SLC4A1 which
codes for Band 3.
HEREDITARY OVALOCYTOSIS
68
In HEREDITARY OVALOCYTOSIS, Increase membrane rigidity due to a tighter binding of Band 3 to _____.
Ankyrin
69
True or False
Hereditary Ovalocytes RBC membranes have decreased elasticity.
True
70
Overhydrated hereditary stomatocytosis (OHS)
HEREDITARY HYDROCYTOSIS
71
What inheritance trait is HEREDITARY HYDROCYTOSIS
Autosomal dominant trait
72
What is the Deficient Protein/ Mutated Gene in HEREDITARY HYDROCYTOSIS
RhAg
73
What is the secondary Deficient Protein/ Mutated Gene in HEREDITARY HYDROCYTOSIS
Stomatin
74
RBC membrane is excessively permeable to Sodium and Potassium at 37oC.
HEREDITARY HYDROCYTOSIS
75
Influx of Na+ into the cell, increase loss of K+ . More water enters the cell causing it
to swell
Hereditary Hydrocytosis Stomatocytosis
76
Dehydrated hereditary stomatocytosis (DHS)
HEREDITARY XEROCYTOSIS
77
WHat trait is HEREDITARY XEROCYTOSIS
Autosomal dominant
78
Deficient Protein/ Mutated Gene: PIEZO 1
Protein, KCNN4
HEREDITARY XEROCYTOSIS
79
Most common form of Stomatocytosis
HEREDITARY XEROCYTOSIS
80
In HEREDITARY XEROCYTOSIS, RBC membrane is excessively permeable to ________.
Potassium
81
Increase loss of K+ with no increase in Sodium. Reduced Intracellular cation
concentration, Water is lost from the cell.
Hereditary Xeroxytosis
82
What disease has the clinical findings of Fetal loss, hydrops fetalis and neonatal hepatitis.
Hereditary Xeroxytosis
83
Rare Autosomal Dominant disorder, mutation in ABCB6 gene.
FAMILIAL PSEUDOHYPERKALEMIA
84
In FAMILIAL PSEUDOHYPERKALEMIA, Excessive loss of RBC K+ at room temperature in ____but not at body temp in ____.
Vitro, vivo
85
Cold induced leakage of Na+ and K+ from the RBCs.
CRYOHYDROCYTOSIS
86
Increased cation permeability, cell swelling, and hemolysis when stored at ____for 24
to 48 hours.
4
87
Rh membrane proteins is absent (Rh-Null) or decreased (Rh-mod).
Rh deficiency syndrome
88
Rare autosomal recessive disorder. Mutation in MTP needed to transfer and assemble lipids
Abetalipoproteinemia (ABL)
89
In ABL, RBC membrane acquires increased S___________ which decreases fluidity of membrane and results in shape change.
Sphingomyelin
90
What trait is MLS?
X-linked disorder
91
Mutations in KX Gene, precursor for Kell Blood Group Antigens
McLeod Syndrome (MLS)
92
In MLS, Reduced expression of Kell Ag, reduced RBC deformability, ________RBC survival
shortened
93
Rare Autosomal recessive, mutaions in Chorein which leads to abnormal membrane structure
Chorea Acanthocytosis (ChoAc)
94
Excess Free Cholesterol accumulates in the RBC membrane. The spleen
remodels the RBC giving long, rigid projections
ACANTHOCYTES
95
- Drying Artifact on Peripheral Blood Smear
- Acute Alcoholism
- Malignancies
- Cardiovascular diseases
Acquired stomatocytosis
96
Acquired- mutations occur after birth
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
97
Intravascular hemolytic anemia from mutations in PIGA Gene encodes GPI, anchor protein.
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
98
In PNH, No GPI, No complement regulatory Proteins CD__and CD__.
CD55 and CD59.
99
Phenotypic mosaicism
PNH
100
No CD55 and CD59 complement attack the RBC, causing i____________ lysis.
intravascular
101
Causes Smooth Muscle Dystonia (Esophageal spasma,dysphagia, erectile dysfunction)
PNH
102
Causes thrombosis (i.e. hepatic- Budd-Chiarri syndrome)
PNH
103
- Chronic renal disease
PNH
104
Subcategories of PNH:
30-50% of circulating Neutrohpils are GPI deficient
Classic PNH
105
Subcategories of PNH:
<20-30% of Neutrophils are GPI deficient
Hypoplastic PNH
106
Subcategories of PNH:
GPI deficient neutrophils is less than 1%V
Subclinical PNH
107
Hemoglobinuria at Night, Hemosidenuria
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
108
What are the test in PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (3)
Sugar Water Test (Sucrose Hemolysis Test) and HAM Test (Acidified Serum Lysis Test), and LapScore
109
Treatment:
binds complement C5, inhibits formation of membrane attack unit.
For what disease?
Eculizumab for PNH
110
Treatment:
Hematopoietic Stem Cell Transplant
PNH
111
In PNH, __________ __________ vaccine before drug administration. (bacteria)
Neiserria meningitidis
112
The most common RBC enzyme defect and prevalence of 5% of the global population.
The highest prevalence where malaria is endemic
G6PD def
113
WHat pattern of inheritance is G6PD def
x-linked
114
G6PD provides the only means to generate _____ needed to protect the cells from
oxidative ______.
NADPH; stress
115
Oxidative agents/stressors in G6PD
Infection, Drugs, Fava Beans
116
In G6PD def:
O___________ converts hemoglobin to methemoglobin, d _________the Hgb solubility of the cell, and precipitates as H______ B______ which adhere to the inner RBC membrane and are removed by hemolysis.
Oxidation; decreases; Heinz Bodies
117
rare, severe hemolytic episode following ingestion of fava beans.
Favism
118
Jaundice appears 2-3 days after birth may lead
to kernicterus.
Neonatal hyperbilirubinemia
119
diagnosed as neonatal hyperbilirubinemia at birth but persists to adulthood.
No Hemoglobinuria, suggests extravascular hemolysis
Chronic hereditary nonspherocytic hemolytic anemia
120
Gold standard for G6PD def
Quantitative Spectrophotometric Assays
121
Rapid Screening for G6PD
Qualitative/ Spot Tests
122
Most common form of hereditary non-spherocytic hemolytic anemia
Pk def
123
What inheritance pattern in PK def?
Autosomal recessive
124
In PK def, Mutation on ____gene that codes for PK in RBCs
PKLR
125
If there is NO Pyruvate Kinase, NO ATP. RBCs are dehydrated, what rbc morphology will form ?
Echinocytes (Burr Cells)
126
Glycolytic Pathway is blocked, increasing 2,3- BPG
Will Shift to ______
Right
127
3rd most common RBC enzyme deficiency.
Pyrimidine 5' nucleotidase type 1
128
In P5'NT-1, B________ s_______ in the cell leading to premature hemolysis.
Basophilic Stippling
