RBC disorders Flashcards
1
Q
what are the 3 general categories of anemia?
A
1) RBC (blood) loss
2) Decreased RBC Survival
3) Decreased RBC Production
2
Q
Young healthy subjects can tolerate rapid loss of _________ with few symptoms
A
500-1000 mL
up to 15-20% of total blood volume
3
Q
what are the symptoms of a blood loss of 1500-2000mL?
A
- all patients are symptomatic
- thirst
- shortness of breath
- loss of consciousness
- sweating
- rapid pulse, decreased blood pressure
- clammy skin
4
Q
Rapid loss of _______ mL produces shock
A
2000-2500
5
Q
what is anemia?
A
- Chronic blood loss
- when the rate of loss exceeds the capacity for RBC regeneration or when iron reserves are depleted
6
Q
________________ due to ulcer or neoplasm, or ______________ are important causes of iron deficiency
A
1) Chronic GI hemorrhage
2) GYN hemorrhage (menorrhagia)
7
Q
Hemolytic anemias are characterized by what?
A
shortened red cell survival and retention of products of red cell destruction (iron)
8
Q
what is Intravascular hemolysis?
give examples:
A
- destruction of RBC within the circulation
- mechanical trauma (e.g., from a defective heart valve)
- hemolytic transfusion reaction
9
Q
what causes hemoglobinemia?
A
Hemoglobin released from RBC into circulation
10
Q
Hemoglobin released from RBC into circulation is bound to ____________, a binding protein, and cleared from the circulation by the liver.
A
haptoglobin
11
Q
A decrease in serum _____________ is a key feature of intravascular hemolysis
A
haptoglobin
12
Q
what happens when plasma hemoglobin levels exceed amount of available haptoglobin?
A
free hemoglobin is excreted in the urine
13
Q
what is the term for excreting free hemoglobin in the urine?
A
hemoglobinuria
14
Q
iron that accumulates in __________ cells in the kidney as a breakdown product of hemoglobin is lost in the urine when these cells are shed
A
proximal tubular
15
Q
what is hemosiderinuria?
A
- brown urine
- when proximal tubular cells of kidney die off and release iron from excreted hemoglobin
16
Q
Conversion of heme (derived from hemoglobin) to bilirubin leads to what 2 conditions?
A
hyperbilirubinemia and jaundice
17
Q
The degree of jaundice during intravascular hemolysis is dependent on what?
A
the functional capacity of the liver and rate of hemolysis
18
Q
T/F: Levels of haptoglobin in cases of intravascular hemolysis are characteristically high
A
FALSE
they are low
19
Q
what is extravascular hemolysis?
A
destruction of RBC in reticuloendothelial system (spleen, liver)
20
Q
what are some examples of extravascular hemolysis
A
Hereditary spherocytosis
sickle cell anemia
erythroblastosis fetalis (antibody-mediated hemolytic disease of the newborn)
21
Q
Damaged or abnormal RBC are removed in the _____, where hemoglobin is broken down intracellularly
A
spleen
22
Q
what happens to free hemoglobin during extravascular hemolysis?
A
hemoglobin breakdown products are increased (hyperbilirubinemia) and jaundice may result
23
Q
Chronically elevated levels of bilirubin can promote formation of _________
A
gallstones
24
Q
what 2 groups are hemolytic anemias classified into?
A
classified by the mechanism of red cell destruction
- intrinsic defects (hemoglobin production, membrane abnormality)
- extrinsic defects (antibody, mechanical trauma)
25
which types of hemolytic anemias are usually inherited? which are caused by acquired abnormalities?
intrinsic = inherited
extrinsic = acquired
26
what are the 4 Intrinsic Defects that cause hemolytic anemia?
1) membrane defects
2) Abnormal hemoglobin
3) lack of globin chains
4) metabolic defects
27
______________ is an intrinsic, extravascular hemolysis
hereditary spherocytosis
28
what is hereditary spherocytosis?
- An inherited defect in the red cell membrane
| - results in less deformability of RBC, so that they are sequestered and destroyed in the spleen
29
The specific defect of hereditary spherocytosis can be a qualitative or quantitative deficiency of ______, a structural protein of the cytoskeleton
spectrin
* this means that the severity of the disease is variable
30
in what pattern is hereditary spherocytosis inherited? At what age does it show?
- Autosomal dominant inheritance in most cases
| - Manifest in adult life
31
what are the pros/cons to removing the spleen in a patient with hereditary spherocytosis?
- Removal of spleen results in normal red cell survival
- but not normal red cell morphology
- after surgery, production of spherocytes continues, but they do less damage
32
this disease is caused by abnormal hemoglobin, and leads to extravascular hemolysis:
sickle cell anemia
33
what is sickle cell anemia?
- An inherited defect (autosomal codominant) in the structure of globin chain
- causes hemoglobin to gel upon deoxygenation
34
The specific defect of SSA is a single base pair substitution in DNA that causes a single amino acid substitution of ___________ for _________
valine for glutamic acid
35
in sickle cell anemia, where on the protein does the single base pair substitution take place?
at position 6 in the beta chain of globin
36
Under what conditions will the abnormal hemoglobin of SSA polymerizes, causing the RBC to assume a "sickle" shape.
low oxygen conditions
37
what are the characteristics of "sickle" shaped RBC's? what problems can they cause?
- cells are rigid and vulnerable to splenic sequestration (decreased survival)
- can also block the microcirculation causing ischemia and/or infarction
38
Sickle cell disease occurs in homozygotes for ____
HbS
39
what are the clinical characteristics of sickle cell anemia?
- severe anemia
| - vaso-occlusive crises, including acute chest syndrome and stroke
40
name the complications associated with SSA?
autosplenectomy
painful crises
leg ulcers
retinal and renal thromboses
41
About __% of blacks in USA have sickle cell trait.
why are most people with the genetic abnormality asymptomatic?
8%
- essentially asymptomatic because less than half of the hemoglobin is abnormal and the concentration of HbS within the RBC is insufficient to cause sickling
42
what condition causes extravascular hemolysis due to Lack of globin chains?
thalassemia
43
what is thalassemia?
- An inherited defect (autosomal codominant)
| - results in diminished or absent synthesis of either the alpha or beta globin chains of hemoglobin
44
what types of genetic mutations cause thalassemia?
1) whole or partial gene deletion
2) mutations in the coding sequence or promotor region
3) mRNA instability
45
The type of thalassemia is named for the ___________ produced in reduced amounts
globin chain
46
what is the result of decreased globin chain production during thalassemia?
results in:
- decreased hemoglobin production
- anemia is the principal clinical manifestation
47
why does thalassemia cause RBC membrane damage and premature destruction of RBC precursors in the marrow and spleen?
due to precipitation of the relative excess of the other globin chain within RBC
(the 2 effects are also called ineffective erythropoiesis and extravascular hemolysis)
48
what are the clinical manifestations of thalassemia?
vary from:
- severe transfusion-dependent anemia and iron overload (thalassemia major)
to
- mild anemia (thalassemia minor)
49
In almost all cases of thalassemia, there is a moderate to marked __________ with target cells and ___________ stippling of the red cells present on the blood smear
microcytosis (low MCV)
basophilic stippling
50
in what groups is thalassemia common?
persons of Mediterranean, African, and Southeast Asian descent
*reduces effects of milaria
51
Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is an example of a _________ defect that causes extravascular hemolysis
metabolic defect
52
how is G6PD inherited? what groups are more likely to have it?
An inherited defect (X-linked) encountered primarily in blacks
53
what are the pathological characteristics of a G6PD deficiency?
red cells are susceptible to oxidant injury by drugs or toxins (antimalarials, sulfonamides, etc.)
54
in G6PD deficiency, The denaturation of ______________________ causes it to precipitate within the cell and attach to the RBC membrane
oxidized hemoglobin
55
what are the effects on the RBC's with a G6PD deficiency? when is the condition symptomatic or asymptomatic?
The RBC membrane's flexibility is reduced, leading to extravascular hemolysis
The condition is asymptomatic in the absence of the oxidant.
56
what are the 3 types of extrinsic defects that cause hemolytic anemia?
1) Immune destruction
2) Mechanical trauma
3) Infections
57
“Bite” cells are the morphologic hallmark for ______________ (a condition) on cytologic exam
G6PD deficiency
58
what are the 3 types of autoimmune (immune destruction) conditions that cause hemolytic anemia
1) Hemolytic disease of the newborn (erythroblastosis fetalis, immune hydrops)
2) Hemolytic transfusion reaction
3) Autoimmune hemolysis
59
what causes Erythroblastosis fetalis (AKA "Hemolytic disease of newborn")
caused by blood group incompatibility between the mother and fetus
60
during Erythroblastosis fetalis, the mother's immune system makes ____________ that cross the placenta and attach to the fetal RBC, resulting in extravascular hemolysis
antibodies (IgG)
61
_____ and _____ antigens (especially anti-D) are most important in the erythroblastosis fetalis disorder
ABO and Rh antigens (especially anti-D)
62
to prevent hemolytic disease of newborns, Rh-negative mothers are given __________ within 72 hours of delivery of an Rh-positive fetus
anti-D (Rhogam)
63
anti-D binds to the _________ fetal cells and removes them from the maternal circulation before the mother can generate an antibody response and become sensitized
Rh-positive
64
______________ disease occurs in group A and B infants born to group O mothers
ABO hemolytic
65
what are the characteristics of Hemolytic transfusion reactions?
- intravascular hemolysis
- transfusion of incompatible red cells into a sensitized patient results in binding of antibody (in patient) to antigen (transfused RBC)
66
what are the effects of hemolytic transfusion reactions?
Activation of coagulation cascade with bleeding, renal failure, shock, and death can occur
67
what are the general characteristics of Autoimmune hemolysis ?
- extravascular hemolysis
| - Patient makes antibodies to his/her own RBCs
68
what can happen during autoimmune hemolysis when antigen binds to RBC's?
- Antibody-coated cells can be lysed (complement activation)
or
removed by the reticuloendothelial system
- Phagocytosis of antibody-coated RBC can lead to partial loss of red cell membrane (spherocytes).
69
what causes Erythroblastosis fetalis (AKA "Hemolytic disease of newborn")
caused by blood group incompatibility between the mother and fetus
70
during Erythroblastosis fetalis, the mother's immune system makes ____________ that cross the placenta and attach to the fetal RBC, resulting in extravascular hemolysis
antibodies (IgG)
71
_____ and _____ antigens (especially anti-D) are most important in the erythroblastosis fetalis disorder
ABO and Rh antigens (especially anti-D)
72
to prevent hemolytic disease of newborns, Rh-negative mothers are given __________ within 72 hours of delivery of an Rh-positive fetus
anti-D (Rhogam)
73
anti-D binds to the _________ fetal cells and removes them from the maternal circulation before the mother can generate an antibody response and become sensitized
Rh-positive
74
______________ disease occurs in group A and B infants born to group O mothers
ABO hemolytic
75
what are the characteristics of Hemolytic transfusion reactions?
- intravascular hemolysis
- transfusion of incompatible red cells into a sensitized patient results in binding of antibody (in patient) to antigen (transfused RBC)
76
what are the effects of hemolytic transfusion reactions?
Activation of coagulation cascade with bleeding, renal failure, shock, and death can occur
77
what are the general characteristics of Autoimmune hemolysis ?
- extravascular hemolysis
| - Patient makes antibodies to his/her own RBCs
78
________________ neutrophils may be seen secondary to the delay in mitotic division during megaloblastic anemia
Hypersegmented
79
how does a Cardiac valve prosthesis cause hemolysis?
- intravascular hemolysis
- Red cells are disrupted by physical trauma as they pass through areas of turbulence and abnormal pressure related to abnormal valve function
80
what happens during disseminated intravascular coagulation?
- RBCs are lysed as they pass through fibrin clots/strands in the microcirculation.
- Loss of large portion of membrane produces schistocytes.
81
list the features of malaria:
- intravascular hemolysis
- Parasites infect RBC and cause lysis of RBC during maturation.
- Varying degrees of intravascular hemolysis are experienced by individual patients.
82
what RBC diseases result from nutritional deficiencies?
- Iron Deficiency Anemia
| - Vitamin B12 and Folate Deficiency
83
_________ is the most common cause of anemia worldwide
Iron deficiency
84
what happens to RBC's when there is a shortage of iron?
Red blood cells become smaller (microcytic) and contain less hemoglobin (hypochromic) than usual
*note: these are the same characteristics as RBC's during Thalassemia (both conditions= lack of funct Hemoglobin)
85
describe the progression of anemia due to iron deficiency?
Anemia develops insidiously
remarkably low levels of hemoglobin can be tolerated with minimal symptoms
86
what type of deficiency causes Megaloblastic anemia?
Vitamin B12 and folate
87
Both B12 and folate are involved either directly or as cofactors in the synthesis of ________
thymidine
88
________________ neutrophils may be seen secondary to the delay in mitotic division during megaloblastic anemia
Hypersegmented
89
Patients with __________ anemia have autoantibodies directed against intrinsic factor
pernicious
90
what 2 disorders are associated with decreased red blood cell production?
Aplastic anemia
Myelophthisic anemia
91
name the characteristics of Aplastic anemia:
Production of all cellular elements of the blood (red cells, white cells, and platelets) is markedly decreased (pancytopenia)
92
what causes aplastic anemia?
Over half of the cases have no known predisposing cause (idiopathic)
- but viruses (hepatitis), drugs (chloramphenicol) and toxins (benzene, radiation) have been implicated
93
Clinical problems of aplastic anemia result from what?
anemia (weakness, fatigue), leukopenia (infections), and decreased platelets (bleeding)
94
The opposite of anemia is __________
polycythemia
95
what causes Relative polycythemia?
occurs with hemoconcentration from dehydration, vomiting, diarrhea, or excessive use of diuretics
96
Primary absolute polycythemia occurs when what occurs?
neoplastic proliferation of red cells (polycythemia vera)
97
secondary absolute polycythemia occurs when what occurs?
increased erythropoietin production
- Cyanotic heart disease, pulmonary disease, living at high altitudes, erythropoietin-producing tumors
98
what causes Myelophthisic Anemia ?
Bone marrow replaced by tumor (metastasis or myeloma) or fibrosis
99
what is the characteristic shape of RBC's during Myelophthisis Anemia?
RBC's seen as “teardrops” on blood smear
100
Along with RBC count, what else is reduced during Myelophthisis Anemia?
Platelets are often also decreased
