Hematopathology 1 Flashcards
(83 cards)
1
Q
Anemia can be described as
A
- Reduction in oxygen carrying capacity of the blood
- Reduction of total circulating red cell mass of RBCs
2
Q
Decrease in tissue oxygen triggers what secretion by renal cells?
A
Erythropoietin
3
Q
Decrease in tissue O2 triggers erythropoietin secretion in renal cells. it leads to..
A
- Compensatory hyperplasia of erythroid precursors in bone marrow. Extramedullary hematopoiesis in severe cases
- Immature cells into circulation (reticulocytosis)
4
Q
What is evaluated on a RBC peripheral blood smear to clue underlying disorders?
A
RBC size, shape, and Hb content (normochromic, hypo chromic)
5
Q
Red cell count for males
A
4.9
6
Q
Red cell count for females
A
4.4
7
Q
Hemoglobin for males
A
16
8
Q
Hemoglobin for females
A
14
9
Q
Hematocrit for males
A
47
10
Q
Hematocrit for females
A
42
11
Q
MCHC for males
A
34
12
Q
MCHC for females
A
34
13
Q
MCV for males
A
95
14
Q
MCV for females
A
95
15
Q
What are 3 ways to lose oxygen carrying capacity?
A
- Bleeding
- Hemolysis
- Diminished erythropoiesis (production)
16
Q
What are symptoms of anemia?
A
Pallor, fatigue, lassitude
17
Q
Symtpoms of hemolytic anemias
A
Hyperbilirubinemia, jaundice, pigmented gallstones
18
Q
Acute blood loss
A
- Severe blood loss: shock
- Normochromic, normocytic anemia
- With adequate iron stores, replacement begins quickly
19
Q
Chronic blood loss
A
GI ulcers, IBD, menstrual irregularities
- Gradual depletion of iron stores (iron deficiency anemia)
20
Q
What are all hemolytic anemias characterized by?
A
- Increased rate of RBC destruction
- Increased rate of erythropoiesis- increased reticulocytes in blood
- Retention of RBC breakdown product: hyperbilirubinemia
- Extramedullary hematopoiesis may occur
21
Q
Most cases of hereditary spherocytosis are
A
Autosomal dominants
22
Q
Hereditary spherocytosis is characterized by
A
- Mutations in various proteins forming the intracellular skeletal meshwork just beneath the surface of RBC plasma membrane
- Ankyrin that connects spectrin meshwork to intrinsic membrane proteins
- Decreased membrane stability
- Loss of membrane, RBCs become spheres
23
Q
There is no cure for hereditary spherocytosis, but the anemia is helped by what?
A
Splenectomy
24
Q
What is the most prevelant hemoglobinopathy?
A
Sickle cell anemia
25
How is sickle cell anemia characterized?
Stucturally abnormal Hb
- Point mutation at #6 codon on B chain, substitutes valine for glutamic acid
26
Sickling increased in tissues with low oxygen, which include
Spleen, bone marrow, areas of inflammation
27
Cells sickle with
Deoxygenation
Reversiible with oxygen, but becomes permanent when repetitive
28
Sickled cells cannot transit spleen and are removed by macrophages. Results in extensive
erythropoiesis with apposition of new bone to expand the marrow, causing hair on end appearance on X rays
29
Sickled cells obstruct
Peripheral capillaries causing painful microinfarcts
30
What is thalassemia?
Heterogenous group of genetic disorders with decreased rate of synthesis Hb
31
One abnormal Beta allele
Thalassemia minor- asymptomatic/mildly symptomatic
32
2 abnormal Beta alleles
Thalassemia major
33
Thalassemia is characterized by
Single base changes in beta gene
34
In thalassemia, alpha chain aggregates and alters
RBC shape so they are removed by macrophages in spleen/bone marrow
35
Hb alpha chains are produced by
2 genes and 4 alleles
36
Alpha thalassemia results from deletions of what?
The alleles
37
Loss of 1 alpha allele
Silent carrier state
38
Loss of 2 alpha alleles
Alpha thalassemia trait- asymptomatic or mildly symptomatic
39
Loss of 3 alpha alleles
B globin chains form tetramers (HbH). Less damage than tetramers of alpha chains, so problem is less severe than thalassemia major
40
Loss of 4 alpha alleles
hydrops fetalis, incompatible with life
41
Thalassemia major becomes apparent when?
HbF levels decline
42
In thalassemia, how does the body attempt to replace RBCs?
- Hepatosplemomegaly, expansion of bone marrow (get skeletal deformities)
43
In thalassemia major, it is sustained by
Blood transfusions.
Iron overload- hemochromatosis- could be fatal
Treat with chelators of iron, bone marrow transplant
44
HbH disease may not require
Transfusions
45
Thalassemia minor has
Hypochromic, microcytic anemia, but a normal lifespan
46
What is G6PD?
enzyme in the hexose monophosphate shunt pathway that plays a key role in protecting cells from oxidative damage, mainly by generating NADPH
47
NADPH in turn keeps glutathione in a
reduced state
48
In G6PD deficiency, RBCs are susceptible to damage by
oxidants
49
Deficiencies in enzymes that maintain adequate levels of GSH increase the risk of
oxidizing (denaturing) Hb
50
In G6PD deficiency, no symptoms unless RBCs are
subjected to oxidants
51
What are immunohemolytic anemias caused by?
antibodies binding to normal or altered RBC membrane antigens
52
What test is used in immunohemolytic anemias?
Coombs test
53
What does a coombs test evaluate?
Presence of anti-RBC antibodies bound to RBCs or free in the circulation
54
Immunohemolytic anemias: IgM activates
COmplement
Intravascular hemolysis or opsonization via C3b
55
Immunohemolytic anemias: IgG acts as opsonin so
RBCs phagocytosed by macrophages in spleen
56
Hemolytic anemia due to mechanical trauma to RBCs can be due to
- Cardiac valve prosthesis
- Narrowing, partial obstruction of small blood vessels due to damage to vessel wall or formation of fibrin clots (SLE, hypertension, cancers, disseminated intravascular coagulation)
57
In hemolytic anemia due to mechanical trauma to RBCs, the damaged RBCs lose parts of cell membrane and are removed by what?
Splenic macrophages
58
Malaria: Have a complex life cycle which includes infecting liver cells, multiplying and in short time showers _________ into the blood stream.
Merozoites
59
Malaria: Merozoites are released from RBCs every 48-72 hours causing
Extensive hemolysis, cyclic fevers, chills, shaking
60
Malaria: Hemolysis results in
Hemoglobinemia, jaundice and hemoglobinuria (blackwater fever)
61
Malaria: Describe splenomegaly
Splenic macrophages increase in number to deal with the parasitized RBCs
62
Malaria: Cerebral vessels engorged with parasitized RBCs, create __________ and __________, convulsions, coma, death
Microthrombi; brain damage
63
What are anemias of diminished erythropoiesis?
- Iron deficiency anemia
- Megaloblastic anemia
- Aplastic anemia
- Myelophthisic anemia
64
Iron deficiency anemia is characterized by negative iron balance, which could be from what?
Low dietary intake of iron, malabsorption syndromes, excessive demand for iron (pregnancy, infancy), chronic blood loss (menorrhagia, GI ulcers, cancers, infections)
65
Iron deficiency anemia onset is
Insidious
Gradual decrease in Fe containing proteins
66
Iron deficiency anemia results in
Hypochromic, microcytic anemia that is usually mild
67
Iron deficiency anemia can cause
Atrophic glossitis, weakness, pallor
68
Iron deficiency anemia: Minimal bone marrow hyperplasia:
Limited by iron availability
69
Anemia of chronic disease typically occurs in chronic diseases with
Long-term systemic inflammation
(Osteomyelitis, bacterial endocarditis, Crohn;s, rheumatoid arthritis, Hodgkin lymphoma)
70
megaloblastic anemias are characterized by a deficiency in
Dietary folate or vitamin B12
( Both involved in DNA synthesis (purines) and their effect on erythropoiesis is similar)
71
Megaloblastic anemias: Delay in DNA synthesis causes a delay in
nuclear maturation and cell division
72
Describe the delay in megaloblastic anemia
- Cytoplasmic components mature normally and continue to accumulate during the delay, resulting in enlarged RBC precursors (megaloblasts) and enlarged RBCs, other cells in body as well
- RBCs are macrocytic and neutrophils are hypersegmented
- Anemia due to slow production reduced total output. Some fail to divide at all, undergo apoptosis
- Pancytopenia
73
Megaloblastic anemia: delay in either vitamin causes what?
Slow turnover of GI epithelium and alimentary tract symptoms can be severe with sore tongue, cheilosis
74
Megaloblastic anemia: Vit B12 deficiency also causes
demyelinating disease of peripheral nerves and spinal cord
75
Megaloblastic anemia: Vit B12 deficiency due to inadequate synthesis or defective function of intrinsic factor is
Pernicious anemia
76
Myelophthisic anemia is anemia caused by what?
Extensive replacement of bone marrow with fibrosis, tumor cells, etc that crowd out normal hematopoietic elements
( Leukemia, multiple myeloma, metastatic cancers, infections, progressive fibrosis of marrow, osteosclerosis)
77
What are symptoms of myelophthisic anemia?
Symptoms of anemia and thrombocytopenia
78
What are symptoms of aplastic anemia?
Symptoms of anemia, petechiae, ecchymoses due to thrombocytopenia and persistent infections (neutropenia)
79
What is pancytopenia?
Anemia, thrombocytopenia and neutropenia
80
Aplastic anemia causes
Pancytopenia
81
Aplastic anemia is
Marrow failure state- suppression of multipotent myeloid stem
82
Aplastic anemia progression is unpredictable because cause may be
fleeting or persistent, Can discontinue a drug, perform bone marrow transplant
83
