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Flashcards in Anemia Deck (120):
1

Hb in males with Anemia

<13.5 g/dl

2

Hb in females with Anemia

<12.5 g/dl

3

Microcytic

MCV<80

4

Normocytic

80<100

5

Macrocytic

100

6

TIBC

Total Transferrin in blood

7

% Saturation

% of transferrin that is bound to Fe

8

Serum Ferritin

How much iron present in storage sites

9

Fe + protoporphyrin =

Heme

10

Fe is absorbed in the

Duodenum

11

enterocytes transport Fe into blood via

Ferroportin

12

What transports iron and delivers it for storage

Transferrin

13

Where is iron stored

Liver and bone marrow macrophages

14

Folate enters the body as

Tetrahydrofolate

15

Folate enters the body and is quickly methylated. In order to participate in the synthesis of DNA precursors it has to lose its methyl group. What takes the methyl group from tetrahydrofolate (folate) to allow it to function

Vitamin B12

16

B12 passes the methyl group (taken from tetrahydrofolate) to what

Homocysteine

17

Methylated homocysteine is

Methionine

18

Folate is absorbed in the

Jejunum

19

How long does it take to develop folate deficiency

Only a few months becuase body stores are minimal

20

Salivary gland enzymes (IE amylase) liberate B12 from animal proteins B12 is then bound to what (also from the salivary gland) and carried through the stomach

R-binder

21

Pancreatic proteases in the duodenum detach B12 from R-binder. B12 binds intrinsic factor (made by stomach parietal cells) in the small bowel, and together, B12 and intrinsic factor are absorbed in the

Ileum

22

How long does it take to develop B12 deficiency

Years because of large hepatic stores

23

What helps distinguish between peripheral destruction of and underproduction of RBCs

Reticulocytes (Normal reticulocyte count is 1-2%)

24

A properly functioning marrow responds to anemia by increasing reticulocytes to

>3%

25

reticulocyte count is corrected by

Multiplying it by Hct/45

26

A corrected reticulocyte count >3% indicates

Functional bone marrow >3% (<3% indicates poor marrow response: underproduction of RBCs)

27

Most common type of anemia

Iron Deficiency Anemia

28

Iron Deficiency Anemia is micro, normo, or macro-cytic

Microcytic (The initial stage of Fe deficiency anemia is normocytic)

29

4 phases of Iron Deficiency Anemia

Phase 1: Storage iron is depleted (Ferritin decreased, TIBC increased), Phase 2: Serum iron is depleted (Serum Fe decreased and % sat decreased), Phase 3: Bone marrow makes fewer but normal-sized RBCs, Phase 4: Microcytic, hypochromic anemia: Bone marrow makes smaller and fewer RBCs

30

What role could gastrectomy have in iron deficiency anemia

Acidity of stomach maintains Fe in the more bioavailable Fe2+ state

31

Clinical Features: Koilonychia (spoon shaped nails), Pica (psychological drive to eat or chew on dirt or other abnormal things)

Iron Deficiency Anemia

32

Lab Findings: Microcytic (MCV

Iron Deficiency Anemia

33

Anemia of Chronic Disease is micro, normo, or macro-cytic

Begins as a normocytic anemia and becomes microcytic as it becomes more severe

34

Most common type of anemia in hospitalized patients

Anemia of Chronic Disease

35

What is Anemia of Chronic Disease

There is enough iron but iron cannot be used because the patient has a chronic inflammatory disease and iron is being sequestered into storage sites by hepicidin. This prevents transfer of Fe from bone marrow macrophages to erythroid precursors. Hepcidin also suppresses erythropoeitin production

36

Lab Findings: increased ferritin, decreased TIBC, decreased serum Fe, decreased % saturation, and increased FEP

Anemia of Chronic Disease

37

Treatment: Anemia of Chronic Disease

Treat inflammation to reduce production of hepcidin. Exogenous erythropoietin is useful in a subset of patients, especially those with cancer

38

What is Sideroblastic Anemia

decreased production of protoporphyrin = low heme = low Hb = microcytic anemia

39

Protoporphyrin is synthesized via a series of reactions: Methylmalonic acid gets converted to succinyl CoA by

B12

40

Protoporphyrin is synthesized via a series of reactions: What is the rate limiting step.

Aminolevulinic acid synthetase (ALAS) converts succinyl CoA to aminolevulinic acid (ALA) using vitamin B6 as a cofactor (rate-limiting step).

41

Protoporphyrin is synthesized via a series of reactions: Aminolevulinic acid dehydrogenase (ALAD) converts what to what

aminolevulinic acid (ALA) to porphobilinogen

42

Additional reactions convert porphobilinogen to protoporphyrin. What attaches protoporphyrin to Fe to make heme [and where does this final reaction occur]

Ferrochelatase (this final reaction occurs in the mitochondria)

43

Congenital defect of what gene most commonly causes Sideroblastic Anemia

Aminolevulinic acid synthetase (ALAS): Enzyme catalyzing the rate limiting step of protoporphyrin synthesis

44

What can denature ALAD and ferrochelatase, leading to Sideroblastic Anemia

Lead poisoning

45

What is required as a cofactor to ALAS (rate limiting step)

B6

46

Both alcoholism and Isoniazid can cause what kind of anemia

Sideroblastic Anemia

47

Iron-laden mitochondria form a ring around the nucleus of erythroid precursors in which anemia

Sideroblastic Anemia (they are known as Ringed sideroblasts)

48

Lab Findings: Prussian blue stain shows ringed sideroblasts. increased ferritin, decreased TIBC, increased serum Fe, increased % saturation

Sideroblastic Anemia

49

decreased SYNTHESIS of the globin chain of Hb = decreased Hb = microcytic anemia. This occurs in

Thalassemia

50

Alpha-Thalassemia is Usually due to gene deletion of two or more of the 4 alpha alleles (one knockout is asymptomatic) that are present on what chromosome

16

51

Cis deletion Alpha-Thalassemia is more common where and is it a better or worse prognosis

Asia and is worse for offspring becuase child could recieve the completely knocked out chromosome

52

Trans deletion Alpha-Thalassemia is more common where and is it a better or worse prognosis

Africa and is better for offspring

53

Clinical features of 2, 3, and 4 gene deletions in Alpha-Thalassemia

2 gene deletions present with mild anemia with slightly increased RBC count. 3 gene deletions result in severe anemia where beta chains form tetramers (HbH) that damage RBCs. 4 deletions is lethal in utero (hydrops fetalis: gamma chains form tetramers called Hb Barts that damage RBCs)

54

Two beta genes are present on what chromosome

11

55

Beta-Thalassemia Minor (Beta/Beta+)

The mildest form that is usually asymptomatic with increased RBC (microcytic and hypochromic ) count

56

Beta-Thalassemia Major (Beta0/Beta0)

The most severe form of the disease that presents with severe anemia a few months after birth (HbF at birth is temporarily protective)

57

Ineffective erythropoiesis and extravascular hemolysis as a result of alpha2, alpha2 tetramers damaging RBCs.

Beta-Thalassemia

58

Microcytic anemia with massive erythroid hyperplasia. Expansion of hematopoeisis into marrow of skull and facial bones. Extramedulary hematopoiesis with HSM, and risk of aplastic crisis with parvovirus B19. Chronic transfusions are necessary which increases the risk for secondary hemochromatosis

Beta-Thalassemia Major

59

Lab Findings: Target cells on blood smear, slightly decreased HbA, increased HbA2 to 5% (normal is 2.5%), and increased HbF to 2% (normal is 1%).

Beta/Beta+ (Beta-Thalassemia Minor)

60

Lab Findings: Microcytic, hypochromic target cells and nucleated red blood cells. Electrophoresis will show little or no HbA, increased HbA2, and increased HbF

Beta0/Beta0 (Beta-Thalassemia Major)

61

HbF

alpha2, gamma2

62

HbA

alpha2, beta2

63

HbA2

alpha2, delta2

64

HbH

beta4 (damages RBCs)

65

Hb Barts

gamma4 (damages RBCs)

66

Megaloblastic anemia with hypersegmented neutrophils (>5 lobes), megaloblastic change in all rapidly-dividing cells in the body.

Folate Deficiency Anemia(Megaloblastic anemia)

67

Causes: Folate Deficiency Anemia(Megaloblastic anemia)

Deficiency in folate inhibits DNA synthesis and can be a result of poor diet, increased demand (pregnancy, cancer, hemolytic anemia), and folate antagonists (methotrexate: inhibits dihydrofolate reductase)

68

Clinical Features: Glossitis (due to decreased turnover of cells of the tongue)

Folate Deficiency Anemia(Megaloblastic anemia)

69

Lab Findings: Macrocytic RBCs and hypersegmented neutrophils on blood smear. decreased serum Folate, increased serum homocysteine. Normal methylmalonic acid

Folate Deficiency Anemia(Megaloblastic anemia)

70

Most commonly due to autoimmune destruction of parietal cells in the stomach leading to intrinsic factor deficiency (pernicious anemia)

B12 Deficiency Anemia (Also can be caused by pancreatic insufficiency, damage to the terminal ileum due to Crohn disease of Diphyllobothrium latum, and dietary deficiency rare, except in vegans)

71

Clinical Features: Glossitis (due to decreased turnover of cells of the tongue), increased risk for thrombosis (due to elevated homocysteine), subacute combined degeneration of the spinal cord (high levels of methylmalonic acid impairs the spinal cord myelinization) leading to poor proprioception and vibratory sensation (posterior column) and spastic paresis (lateral corticospinal tract)

B12 Deficiency Anemia

72

Lab Findings: Macrocytic RBCs and hypersegmented neutrophils on blood smear. decreased serum B12, increased homocysteine, and increased methylmalonic acid

B12 Deficiency Anemia(methylmalonic acid is increased because it cant be converted to succinyl CoA without B12)

73

Lacks hypersegmented Neutrophils, and is caused by alcoholism, liver disease, or drugs (5-FU)

Macrocytic anemia

74

Membrane blebs are formed and lost over time: loss of membrane renders cells round (spherocytes instead of disc-shaped). Spherocytes are less able to maneuver through splenic sinusoids and are consumed by splenic macrophages -> anemia

Hereditary Spherocytosis (Normocytic, Extravascular)

75

Causes: Hereditary Spherocytosis (Normocytic, Extravascular)

Inherited defect Of RBC cytoskeleton-membrane tethering proteins (most commonly spectrin, ankyrin, or band 3.1)

76

Clinical Features: Normocytic anemia with splenomegaly, jaundice with unconjugated bilirubin, increased risk for bilirubin gallstones (extravascular hemolysis), and increased risk for aplastic crisis with parvovirus B19 infection of erythroid precursors

Hereditary Spherocytosis (Sickle Cell Disease is associated with a shrunken fibrotic spleen)

77

Lab Findings: Spherocytes with loss of central pallor, increased RDW and mean corpuscular hemoglobin concentration (MCHC). Diagnosed by osmotic fragility test, which reveals increased spherocyte fragility in hypotonic solution.

Hereditary Spherocytosis (Normocytic, Extravascular)

78

Treatment: Hereditary Spherocytosis (Normocytic, Extravascular)

Splenectomy; anemia resolves but spherocytes persist and Howell-Jolly bodies (fragments of nuclear material in RBCs) emerge on blood smear

79

Causes: Sickle Cell Anemia (Normocytic, Extravascular)

Autosomal recessive mutation in Beta chain of hemoglobin; a single amino acid change replaces normal glutamic acid (hydrophilic) with valine (hydrophobic). Sickle cell disease arises when two abnormal Beta genes are present; results in >90% HbS in RBCs. HbS polymerizes when deoxygenated; polymers aggreagate into needle-like structures, resulting in sickle cells.

80

Aggravating/Alleviating factors of sickling in Sickle Cell Anemia (Normocytic, Extravascular)

Increased risk of sickling occurs with hypoxemia, dehydration, and acidosis. HbF protects against sickling

81

The presence of one mutated and one normal Beta chain and results in < 50% HbS in RBCs (HbA is slightly more efficiently produced than HbS).

Sickle Cell Trait

82

Metabisulfite screen

Causes cells with any amount of HbS to sickle; positive in both sickle cell disease and trait.

83

Lab Findings: 90% HbS, 8% HbF, 2% HbA2, no HbA

Sickle Cell Anemia (Normocytic, Extravascular)

84

Lab Findings: 55%HbA, 43% HbS, 2% HbA2

Sickle Cell Trait

85

Clinical features: Massive erythroid hyperplasia, Dactylitis, Autosplenectomy, Renal papillary necrosis, extramedullary hematopoiesis with hepatomegaly, increased risk of aplastic crisis with parvovirus B19 infection

Sickle Cell Anemia (Normocytic, Extravascular)

86

Autosomal recessive mutation in the Beta chain of hemoglobin. Normal glutamic acid is replaced by lysine.

Hemoglobin C Anemia (Normocytic, Extravascular)

87

Acquired defect in myeloid stem cells resulting in absent glycosylphosphatidylinositol (GPI) that renders cells susceptible to destruction by complement

Paroxysmal Nocturnal Hemoglobinuria (Normocytic, Intravascular)

88

In Paroxysmal Nocturnal Hemoglobinuria (Normocytic, Intravascular), hemolysis occurs episodically, often at night during sleep becuase

Mild respiratory acidosis with shallow breathing during sleep that activates complement

89

Clinical features: RBCs, WBCs, and platelets are lysed. Intravascular hemolysis leads to hemoglobinemia & hemoglobinuria. Hemosiderinuria is seen days after hemolysis.

Paroxysmal Nocturnal Hemoglobinuria (Normocytic, Intravascular)

90

What is the main cause of death in Paroxysmal Nocturnal Hemoglobinuria (Normocytic, Intravascular)

Thrombosis of the hepatic, portal, or cerebral veins (Destroyed platelets release cytoplasmic contents into circulation, inducing thrombosis)

91

Lab Findings: Sucrose test is used to screen for disease (confirmatory test in the acidified serum test or flow cytometry to detect lack of CD55 (DAF) on blood cells.

Paroxysmal Nocturnal Hemoglobinuria (Normocytic, Intravascular)

92

X-Linked recessive disorder resulting in reduced half-life of G6PD renders cells susceptible to oxidative stress

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (Normocytic, Intravascular)

93

Clinical presentation: Presents with hemoglobinuria and back pain hours after exposure to oxidative stress.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (Normocytic, Intravascular)

94

Variant with markedly reduced half-life of G6PD leading to marked intravascular hemolysis with oxidative stress.

Mediterranean variant Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (Normocytic, Intravascular)

95

Mildly reduced half-life of G6PD leading to mild intravascular hemolysis with oxidative stress.

African Variant Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (Normocytic, Intravascular)

96

Decay accelerating factor (DAF) on the surface of blood cells protects against complement-mediated damage by inhibitng

C3 convertase

97

DAF is secured to the cell membrane by what

glycosylphosphatidylinositol (GPI), an anchoring protein

98

An antioxidant that neutralizes H2O2, but becomes oxidized in the process

Glutathione

99

What is needed to regenerate reduced glutathione

NADPH (a by-product of G6PD)

100

Antibody-mediated (IgG or IgM) destruction of RBCs.

Immune Hemolytic Anemia (Normocytic, Intravascular)

101

Type of hemolysis in Immune Hemolytic Anemia: IgG-mediated disease vs IgM-mediated disease

IgG-mediated disease (warm agglutinin) usually involves extravascular hemolysis. IgM-mediated disease (cold agglutinin) usually involves intravascular hemolysis.

102

Most common cause of cold agglutinin hemolytic anemia

SLE

103

Warm agglutinin hemolytic anemia is associated with

mycoplasma pneumoniae and infectious mononucleosis

104

Anti-IgG is added to patient RBCs; agglutination occurs if RBCs are already coated with antibody. Confirms the presence of antibody-coated RBCs

Direct Coombs test

105

Anti-IgG and test RBCs are mixed with the patient serum; agglutination occurs if serum antibodies are present. Confirms the presence of antibodies in patient serum.

Indirect Coombs test

106

Occurs with microthrombi (TTP-HUS, DIC, HELLP), prosthetic heart valves, and aortic stenosis. Microthrombi produce schistocytes on blood smear

Microangiopathic Hemolytic Anemia (Normocytic, Intravascular)

107

RBCs rupture as a part of the plasmodium life sycle, resulting in intravascular hemolysis and cyclical fever. Spleen also consumes some infected RBCs, results in mild extravascular hemolysis

Malaria (Normocytic, Intravascular)

108

Infection of RBCs and liver with plasmodium is transmitted by what

Female anopheles misquito.

109

daily fever

P Falciparum

110

Fever every other day

P Vivax and P Ovale

111

Parvovirus B19

Infects progenitor red cells and temporarily halts erythropoiesis, leading to significant anemia in the setting of preexisting marrow stress (IE sickle cell anemia).

112

Treatment: Parvovirus B19 (Underproduction)

Treatment is supportive (infection is self-limited)

113

Damage to hematopoietic stem cells, resulting in pancytopenia (anemia, thrombocytopenia, and leukopenia) with low reticulocyte count. Etiologies include drugs or chemicals, viral infections, and autoimmune damage.

Aplastic Anemia (Underproduction)

114

Biopsy reveals an empty, fatty marrow

Aplastic Anemia (Underproduction)

115

Pathologic process (ie metastatic process) that replaces bone marrow, impairing hematopoiesis, and resulting in pancytopenia

Myelophthisic Process (Underproduction)

116

Inheritance of Sickle Cell Disease

Autosomal Recessive

117

Inheritance of Hemoglobin C Disease

Autosomal Recessive

118

Inheritance of G6P Deficiency

X-linked Recessive

119

CD59

protectin: binds the membrane attack complex and prevents C9 from binding to the cell

120

CD55

Decay-accelerating factor (DAF): disrupts formation of C3 convertase