Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

WILLIAM'S HEMATOLOGY > 42 Folate, Cobalamin and Megaloblastic Anemias > Flashcards

42 Folate, Cobalamin and Megaloblastic Anemias Flashcards

1
Q

To form a functional compound, folates must be in the reduced ____________________ form

A

Tetrahydrofolate form (FH4)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Enzyme that catalyzes both FA→FH2 and FH2→FH4

A

Dihydrofolate reductase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Stable form of folic acid and the form preferred for clinical use

A

N5-formyl FH4, also called citrovorum factor, leucovorin, or folinic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

The richest sources of folic acid are

A

Dark green leafy vegetables

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Meat, with the exception of_______, is generally not a good source of folate.

A

Liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

In the normal adult, the recommended daily allowance (RDA) for folate is expressed as

A

Dietary folate equivalents (DFEs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

One microgram of food folate is the dietary equivalent of_____mcg folic acid added to food

A

0.6 mcg folic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

The officially recommended dietary allowance of food folate expressed as DFEs for an adult is ___ mg

A

0.4 mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

The body is thought to contain approximately _____ of folate.

A

5 mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

When folate intake is reduced to _____ mcg/day, megaloblastic anemia develops in approximately 4 months.

A

5 mcg/day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Folate requirements in pregnanancy

A

600 mcg/day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Folate requirements in lactating women

A

500 mcg/day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Among the several 1-carbon transfers mediated by folic acid, the transfer that is the most important clinically is the

A

Methylation of deoxyuridylate to thymidylate

This reaction is an essential step in the synthesis of DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

The methylation of deoxyuridylate to thymidylate is catalyzed by the enzyme

A

Thymidylate synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Intracellular folates exist primarily as _________________

A

Polyglutamate conjugates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Inside the cells, the polyglutamate chain is sequentially built up by an ATP-dependent

A

Folylpoly-γ-glutamyl synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

TRUE OR FALSE

Folylpolyglutamates are superior to monoglutamates as substrates for folate-dependent enzyme reactions.

A

TRUE

Folylpolyglutamates are superior to monoglutamates as substrates for folate-dependent enzyme reactions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

The principal sites of folate absorption

A

Duodenum and proximal jejunum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Because only folylmonoglutamate appears in plasma, all folylpolyglutamates must first be hydrolyzed by the enzyme _________ during absorption across the intestine.

A

Glutamate carboxypeptidase II (folate hydrolase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Lysosomal carboxypeptidases that are not involved in absorption of folates from the intestine, but which play a role in the release of folate from storage sites in the liver and kidney

A

γ-glutamyl hydrolases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Folate receptors that despite its missing cytoplasmic extension, is effective in mediating endocytosis

A

Folate receptor-α

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

A probenecid-inhibitable organic anion carrier that, among other functions, carries reduced folates and methotrexate in and out of the cytoplasm

A

Membrane folate transporter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

The principal form of the cobalamin in tissues and in blood

A

N5-methyl form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Breakdown product of folic acid metabolism

A

p-Aminobenzoylglutamate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Folate-binding proteins of serum and milk can be detected in approximately ___% of normal individuals

A

15%

Found at increased levels in some pregnant women, women taking oral contraceptives, folate-deficient alcoholics (but not patients with cobalamin deficiency), and patients with uremia, hepatic cirrhosis, and chronic myelogenous leukemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Folate bound to the milk folate binder in suckling animals is absorbed chiefly in the_______, rather than the jejunum, the principal site of absorption of free folate.

A

Ileum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

The cobalamin molecule has a porphyrin-like near-planar macrocycle known as_______

A

Corrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

The usual therapeutic form of cobalamin

A

Cyanocobalamin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Four cobalamins are important in animal cell metabolism

A

Cyanocobalamin (CnCbl; vitamin B12)
Hydroxocobalamin (OHCbl) or aquocobalamin (HOHCbl)
Adenosylcobalamin (AdoCbl)
Methylcobalamin (MeCbl)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

2 cobalamins are alkyl derivatives that are synthesized from OHCbl and serve as coenzymes

A

Adenosylcobalamin (AdoCbl)
Methylcobalamin (MeCbl)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

The major form of cobalamin in human blood plasma

A

MeCbl

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

TRUE OR FALSE

Cobalamin is known to be synthesized in plants and its presence in foods of plant origin are believed to have come from microbial contamination or through a symbiotic relationship with bacteria.

A

FALSE

Cobalamin is not known to be synthesized in plants and its presence in foods of plant origin are believed to have come from microbial contamination or through a symbiotic relationship with bacteria.

Foods that contain cobalamin are of animal origin: meat, liver, seafood, and dairy products.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Total body content of cobalamin

A

2–5 mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Amount of cobalamin found in liver

A

1 mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

TRUE OR FALSE

Relative to the daily requirement, body reserves of cobalamin are much larger than those of folate.

A

TRUE

Relative to the daily requirement, body reserves of cobalamin are much larger than those of folate.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

The official RDA for cobalamin among adults

A

2.4 mcg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

A mitochondrial enzyme that participates in the disposal of the propionate formed during the breakdown of valine, isoleucine, and odd-carbon fatty acids

A

Methylmalonyl Coenzyme A Mutase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Participates in cobalamin-dependent synthesis of methionine from homocysteine

Also serves as a mechanism critical for converting N5-methyltetrahydrofolate to tetrahydrofolate required for synthesis of polyglutamates as well as other important 1-carbon adducts of folate

A

N5-Methyltetrahydrofolate-Homocysteine Methyltransferase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

TRUE OR FALSE

The megaloblastic anemia of cobalamin deficiency also is variably corrected by folic acid supplementation even if no cobalamin is given, although the remission is partial and only temporary.

A

TRUE

The megaloblastic anemia of cobalamin deficiency also is variably corrected by folic acid supplementation even if no cobalamin is given, although the remission is partial and only temporary.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

TRUE OR FALSE

The anemia of folate deficiency is generally helped by cobalamin

A

FALSE

The anemia of folate deficiency is generally not helped at all by cobalamin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Two explanations have been proposed to account for the folate responsiveness of cobalamin-deficient megaloblastic anemia:

A

Methylfolate Trap Hypothesis

Formate Starvation Hypothesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Hypothesis based on the fact that the folate-requiring enzyme N5-methyl FH4–homocysteine methyltransferase is also dependent on cobalamin

Hypothesis predicts that in cobalamin deficiency tissue levels of N5-methyl FH4 are abnormally high and those of other forms of folate are abnormally low

A

Methylfolate Trap Hypothesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

This theory is based on the diminished capacity of cobalamin-deficient lymphoblasts to incorporate formaldehyde into purine and methionine and on experiments showing that N5-formyl FH4 is more effective than FH4 at correcting some of the abnormalities in folate metabolism seen in cobalamin deficiency.

A

Formate Starvation Hypothesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Human intrinsic factor is a glycoprotein (Mr approximately 44,000) encoded by a gene on _________________

A

Chromosome 11

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Promotes absorption uptake of cobalamin by ileum

Source: Gastric parietal cells

A

Intrinsic factor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Promotes uptake of cobalamin by cells

Source: Probably all cells

A

Transcobalamin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Promotes uptake of cobalamin by cells

Source: Probably all cells

A

Transcobalamin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Helps dispose of cobalamin analogues; possible antimicrobial
function(?)

Source: Exocrine glands, phagocytes

A

Haptocorrin

(previously known as R proteins or TC I and TC III)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

TRUE OR FALSE

Cobalamin binds much more tightly to HC than to intrinsic factor at the acid pH of the stomach

A

TRUE

Cobalamin binds much more tightly to HC than to intrinsic factor at the acid pH of the stomach

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

The intrinsic factor receptor, located in the microvillus pits of the ileal mucosa brush border

A

Cubilin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

The ileal cubilin receptor complex consists of 2 proteins:

A

Cubilin (CUB) and amnionless (AMN)

“CUBAM complex”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

In the portal blood, the cobalamin is complexed with a cobalamin-transporting protein known as

A

Transcobalamin (TC) previously known as transcobalamin II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

The protein with which cobalamin given parenterally associates almost immediately

A

Transcobalamin (TC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

This receptor belongs to the low-density lipoprotein receptor family and its internalization involves megalin

A

CD320

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Bind cobalamin but lack intrinsic factor activity, that is, they are unable to promote the intestinal absorption of the vitamin

Carries most (70–90%) of the circulating cobalamin

A

Haptocorrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Current assays use ______________ as the binder and give more reliable values for serum cobalamin.

A

Intrinsic factor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Shows some evidence of improved specificity compared with the standard cobalamin assay for identifying true cobalamin deficiency, although the assays appear to be generally comparable with respect to sensitivity.

A

Holotranscobalamin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Conditions with Increased haptocorrin (transcobalamin I, R protein)

A

Myeloproliferative disorders
Polycythemia vera
Myelofibrosis
Benign neutrophilia
Chronic myelocytic leukemia
Hepatoma (occasionally)
Metastatic cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Conditions with Increased transcobalamin

A

Liver disease
Inflammatory disorders
Gaucher disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Morphologic hallmark of megaloblastic anemias

A

Presence of megaloblastic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Cell with a large horseshoe-shaped nucleus, sometimes irregularly shaped, containing ragged open chromatin

A

Giant metamyelocyte

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

The most common causes worldwide of megaloblastic anemia

A

Folate deficiency and cobalamin deficiency

62
Q

TRUE OR FALSE

Megaloblastic cells have much more cytoplasm and RNA than do their normal counterparts, but they have a relatively normal amount of DNA, suggesting that cytoplasmic constituents (RNA and protein) are synthesized faster than is DNA.

A

TRUE

Megaloblastic cells have much more cytoplasm and RNA than do their normal counterparts, but they have a relatively normal amount of DNA, suggesting that cytoplasmic constituents (RNA and protein) are synthesized faster than is DNA.

63
Q

The earliest observable change in red cell indices in megaloblastic anemia is

A

Increase in the red cell distribution width

64
Q

Typically, more than _________% of the neutrophils have 5 lobes

A

more than 5%

65
Q

TRUE OR FALSE

Neutrophil hypersegmentation was found to be a sensitive test for mild cobalamin deficiency

A

FALSE

Neutrophil hypersegmentation was not found to be a sensitive test for mild cobalamin deficiency

66
Q

Specific therapy corrects these abnormalities, usually within _____ days, although some abnormalities do not disappear for months.

A

2 days

67
Q

Plasma bilirubin, iron, and ferritin levels are (increased or decreased).

A

Increased

68
Q

TRUE OR FALSE

In megaloblastic anemia LDH-1 is greater than LDH-2, whereas in other anemias LDH-2 is greater than LDH-1.

A

TRUE

In megaloblastic anemia LDH-1 is greater than LDH-2, whereas in other anemias LDH-2 is greater than LDH-1.

69
Q

Megaloblastic anemia is associated with two pathophysiologic abnormalities:

A

Ineffective erythropoiesis (exaggerated apoptosis of precursor cells) and hemolysis

70
Q

Related to ingestion of wheat gluten

Findings include weight loss; glossitis; other signs of a generalized vitamin deficiency; diarrhea; and passage of light-colored, bulky stools with a particularly foul odor caused by steatorrhea.

A

Nontropical sprue (celiac disease in children)

71
Q

TRUE OR FALSE

Clinically and pathologically, tropical sprue is like nontropical sprue, except that tropical sprue is more severe in the distal small intestine.

A

TRUE

Clinically and pathologically, tropical sprue is like nontropical sprue, except that tropical sprue is more severe in the distal small intestine.

72
Q

During pregnancy folate requirements increase ________-fold because of transfer of folate to the growing fetus, which draws down maternal folate stores.

A

5- to 10-fold

73
Q

The major cause of the megaloblastic anemia of pregnancy

A

Folate deficiency

74
Q

Specific features of folate deficiency:

A

(a) a history and laboratory studies indicating folate deficiency,
(b) absence of the neurologic signs of cobalamin deficiency, and
(c) a full response to physiologic doses of folate.

75
Q

The earliest specific indicator of folate deficiency

A

Low serum or plasma folate

76
Q

A better indicator of the tissue folate status

Reflects folate status over the preceding 2–3 months

A

Red cell folate

77
Q

In folate deficiency, uncomplicated by causes of microcytosis, the MCV is usually higher than ______ fL.

A

110 fL

78
Q

TRUE OR FALSE

A full hematologic response to physiologic doses of folate (ie, 200 mcg daily) distinguishes folate deficiency from cobalamin deficiency, in which a response occurs only at pharmacologic doses of folate (typically 5 mg daily or more).

A

TRUE

A full hematologic response to physiologic doses of folate (ie, 200 mcg daily) distinguishes folate deficiency from cobalamin deficiency, in which a response occurs only at pharmacologic doses of folate (typically 5 mg daily or more).

This is not recommended as a diagnostic test because neurologic problems may develop in cobalamin-deficient patients treated with folate alone.

79
Q

The diagnosis of nontropical sprue rests on

A

(a) the demonstration of malabsorption,
(b) a jejunal biopsy showing villus atrophy, and
(c) the response to a gluten-free diet

80
Q

Consumption of _________ can not only cause folate deficiency with resulting megaloblastic anemia but also can cause vitamin B6 deficiency and present as a combined clinicopathologic picture of megaloblastic and sideroblastic anemia.

A

Goat’s milk

81
Q

A close association exists between mild folate deficiency and congenital anomalies of the fetus, most notably________________, but also abnormalities involving the heart, urinary tract, limbs, and other sites

A

Defects in neural tube closure

A portion of the neural tube closure defects are associated with antibodies against folate receptors that may be overcome by higher folate intake

82
Q

TRUE OR FALSE

A mildly decreased homocysteine level is a major independent risk factor for atherosclerosis and venous thrombosis, possibly because of an effect on the vascular endothelium.

A

FALSE

A mildly elevated homocysteine level is a major independent risk factor for atherosclerosis and venous thrombosis, possibly because of an effect on the vascular endothelium.

83
Q

Treatment for tropical sprue

A

Usual doses of folate, plus cobalamin if indicated

To prevent relapse, treatment should be maintained for at least 2 years.

Broad-spectrum antibiotics are helpful adjuncts, although antibiotics alone fail to correct the condition.

84
Q

Dosage of folate among pregnant women

A

400 mcg of folate per day

85
Q

Administration of _____________ can prevent or greatly diminish the major side effects without reducing the therapeutic effect of low-dose methotrexate.

A

Folic or folinic acid

86
Q

A condition characterized by failure of gastric intrinsic factor production

Gastric manifestations include achlorhydria, acquired intrinsic factor deficiency previously demonstrable through showing malabsorption of cobalamin by the Schilling test, and an increased incidence of certain malignancies.

A

Pernicious Anemia

87
Q

In patients with PA, antibodies occur that recognize the _______________

A

H+/K+- ATPase

88
Q

Types of antibodies in Pernicious Anemia

A

Antibodies to intrinsic factor (“type I,” or “blocking,” antibodies

Antibodies to intrinsic factor–cobalamin (Cbl) complex (“type II,” or “binding,” antibodies)

89
Q

The disease is associated with human leukocyte antigen types____________ and with blood group _______

A

Human leukocyte antigen types A2, A3, B7, and B12

Blood group A

90
Q

In Pernicious Anemia, there is ______fold increase in the incidence of gastric cancer

A

Twofold

91
Q

Measurement of ________________ in serum represents the only available method to confirm a diagnosis of PA

A

Antiintrinsic factor antibodies

92
Q

After total gastrectomy, cobalamin deficiency develops within _______ years

A

5 or 6 years

93
Q

TRUE OR FALSE

Postgastrectomy patients with low serum cobalamin levels usually have low serum iron levels, in contrast to the high iron levels otherwise typical of cobalamin deficiency.

A

TRUE

Postgastrectomy patients with low serum cobalamin levels usually have low serum iron levels, in contrast to the high iron levels otherwise typical of cobalamin deficiency.

94
Q

A gastrin-producing tumor, usually in the pancreas, stimulates the gastric mucosa to secrete immense amounts of HCl

The major clinical problem is a severe ulcer diathesis.

A

Zollinger-Ellison Syndrome

95
Q

A state of cobalamin malabsorption with megaloblastic anemia caused by intestinal stasis from anatomic lesions (strictures, diverticula, anastomoses, surgical blind loops) or impaired motility (scleroderma, amyloid)

Serum cobalamin is low, but intrinsic factor secretion is normal.

Corrected by antibiotic treatment

A

“Blind Loop Syndrome”

96
Q

Another cause of cobalamin deficiency is infestation with this fish tapeworm

A

Diphyllobothrium latum

97
Q

It may take _______ years for an individual consuming a vegan diet to manifest features of cobalamin deficiency.

A

10–20 years

98
Q

The neurologic lesions of cobalamin deficiency result from

A

Deranged methyl group metabolism

99
Q

The earliest signs of cobalamin deficiency, which precede other neurologic findings by months, are

A

Loss of position sense in the second toe and loss of vibration sense for a 256-Hz but not a 128-Hz tuning fork

100
Q

Left untreated, the neurologic disorder progresses to spastic ataxia resulting from demyelination of the dorsal and lateral columns of the spinal cord, so-called

A

Combined system disease

101
Q

Frank psychosis in cobalamin deficiency has been given the sobriquet

A

Megaloblastic madness

102
Q

The neurologic lesions of cobalamin deficiency can be detected by

A

Magnetic resonance imaging (MRI)

***hyperintensity of the white matter

103
Q

Cases of thrombotic microangiopathy with severe vitamin B12 deficiency resulting from the inborn errors of metabolism have been described and referred to as

A

cblC or cblG disease

104
Q

Characterized by mutation in the MTR gene leading to a dysfunctional methionine synthase enzyme

A

cblG

105
Q

Disease involves a defect in the enzyme responsible for conversion of cobalamin into its metabolically active reduced forms causing accumulation of homocysteine

A

cblC

106
Q

Conditions where cobalamin levels are usually normal

A

Cobalamin deficiency resulting from exposure to nitrous oxide, TC deficiency, and inborn errors of cobalamin metabolism

Patients with high HC levels resulting from myeloproliferative diseases

107
Q

Plasma cobalamin levels may be low in the presence of normal tissue cobalamins in

A

Vegetarians, in individuals taking megadoses of ascorbic acid, in pregnancy (25%), in the presence of HC deficiency,and in megaloblastic anemia resulting from folate deficiency (30%)

108
Q

The fraction of the cobalamin in plasma that is bound to TC

Fraction that is functionally important and also better reflects the integrity of the cobalamin absorptive status of an individual

A

Plasma or Serum Holotranscobalamin

109
Q

A reliable indicator of cobalamin deficiency

A

Methylmalonic aciduria

**In cobalamin deficiency, urine methylmalonate usually is elevated.

110
Q

Indicators of tissue cobalamin deficiency

A

Plasma or serum methylmalonic acid and homocysteine

Levels are high in more than 90% of cobalamin-deficient patients and rise before plasma cobalamin falls to subnormal levels

111
Q

TRUE OR FALSE

Homocysteine measurement is less sensitive and more specific

A

FALSE

Methylmalonic acid measurement is both more sensitive and more specific

112
Q

Polymorphism results in higher methylmalonic acid concentrations unrelated to B12 status

A

3-hydroxyisobutyryl- CoA hydrolase (HIBCH)

113
Q

Previous “gold standard” for assessment of cobalamin absorption

A

Schilling test

114
Q

Typical treatment schedule for cobalamin deficiency

A

1000 mcg cobalamin intramuscularly daily for 2 weeks, then weekly until the hematocrit is normal, and then monthly for life

115
Q

Treatment schedule for cobalamin deficiency with neurologic manifestations

A

1000 mcg every 2 weeks for 6 months

116
Q

Transfusion occasionally is required when the hematocrit is less than ______% or the patient is debilitated, infected, or in heart failure.

A

less than 15%

117
Q

Response to Treatment and Therapeutic Trial

Within _____ hours, the marrow begins to change from megaloblastic to normoblastic, a process that is complete in ______ days.

A

12 hours

2–3 days

118
Q

Response to Treatment and Therapeutic Trial

Blood hemoglobin concentration becomes normal within _____ months

A

1–2 months

119
Q

TRUE OR FALSE

Cobalamin deficiency does not respond to a physiologic dose of folate (100–400 mcg/ day), although this dose produces a maximal response in folate deficiency.

A

TRUE

Cobalamin deficiency does not respond to a physiologic dose of folate (100–400 mcg/ day), although this dose produces a maximal response in folate deficiency.

120
Q

Larger doses of folate ________ (mg/day) can produce a reticulocytosis and partially or temporarily correct the anemia in cobalamin deficiency.

A

5–15 mg/day

To avoid the risk of masking an underlying cobalamin deficiency by inducing a hematologic remission in response to folate, doses in excess of 1 mg folic acid daily should be shunned until an underlying cobalamin deficiency has been ruled out.

121
Q

TRUE OR FALSE

Cobalamin administration is not necessary after total gastrectomy

A

FALSE

Cobalamin administration is not necessary after partial gastrectomy

Cobalamin should always be given after total gastrectomy.

122
Q

Treatment for Blind Loop Syndrome

A

Parenteral cobalamin therapy

1 week to oral broad-spectrum antibiotics (cephalexin monohydrate [Keflex] 250 mg QID plus metronidazole 250 mg TID for 10 days)

Surgical correction

123
Q

Treatment for Fish Tapeworm

A

50 mg/kg of niclosamide

5–10 mg/kg of praziquantel

124
Q

The most common cause of acute megaloblastic anemia

A

N2O anesthesia

125
Q

Inhibitors of dihydrofolate reductase

A

Aminopterin and methotrexate

126
Q

Cause irreversible inhibition of thymidylate synthase

A

5-fluorouracil and 5-fluorodeoxyuridine

127
Q

Inhibit dihydroorotate dehydrogenase

A

Leflunomide for inflammatory arthritis and teriflunomide for multiple sclerosis

128
Q

Toxicity caused by dihydrofolate antagonists is treated with

A

Folinic acid (N5-formyl FH4)

129
Q

An antifolate approved for use in mesothelioma and for treatment of non–small cell lung cancer

A

Pemetrexed

130
Q

A dihydrofolate reductase inhibitor that is designed to act on the microbial rather than the mammalian enzyme

A

Trimethoprim

131
Q

Cobalamin malabsorption occurs in 4 childhood conditions associated with a genetic component:

A

(a) cobalamin malabsorption in the presence of normal intrinsic factor secretion,
(b) congenital abnormality of intrinsic factor,
(c) TC deficiency, and
(d) true PA of childhood.

132
Q

An inherited failure of transport of the intrinsic factor–Cbl complex by the ileum, usually accompanied by proteinuria, mostly of albumin

It may be the most common cause of cobalamin deficiency in infancy in some populations.

A

Imerslund- Gräsbeck disease

133
Q

Affected genes in Imerslund- Gräsbeck disease

A

CUBN

AMN

134
Q

An autosomal recessive disease in which parietal cells fail to produce functionally normal intrinsic factor

Patients present with irritability and megaloblastic anemia when cobalamin stores (<25 mcg at birth) are exhausted.

A

Congenital Intrinsic Factor Deficiency

135
Q

An autosomal recessive disorder causing a flagrant megaloblastic anemia that generally presents in early infancy.

The disease is dangerously deceptive because it results from a very severe deficiency of tissue cobalamin, usually with serum cobalamin levels in the reference range because most of the plasma cobalamin is bound to HC, resulting in a misleading test result if reliance is placed simply on serum cobalamin measurement.

A

Transcobalamin Deficiency

136
Q

Condition where AdoCbl production is impaired but MeCbl production is normal

A

cblA and cblB

Methylmalonic Aciduria Only (cblA, cblB, and cblH)

137
Q

Methionine synthase is missing or defective

A

cblG

Homocystinuria Only (cblE and cblG)

138
Q

Results from failure to reactivate methionine synthase that was inactivated by oxidation of its bound cobalamin

A

cblE

Homocystinuria Only (cblE and cblG)

139
Q

These patients have both hyperhomocysteinemia and methylmalonic acidemia

A

Methylmalonic Aciduria and Homocystinuria (cblC, cblD, and cblF)

140
Q

The most common of the cobalamin inborn errors

A

cblC

141
Q

The defect lies in an inability to release cobalamin from lysosomes

A

cblF

142
Q

A rare inherited disorder in which patients cannot absorb folate from the gastrointestinal tract or transport it across the choroid plexus and into the cerebrospinal fluid.

The molecular basis for this disorder is caused by abnormalities in the proton-coupled folate transporter.

A

Hereditary Folate Malabsorption

143
Q

TRUE OR FALSE

The megaloblastic anemia in Dihydrofolate Reductase Deficiency responds to folinic acid but not to folic acid.

A

TRUE

The megaloblastic anemia in Dihydrofolate Reductase Deficiency responds to folinic acid but not to folic acid.

144
Q

In this rare autosomal recessive disorder, there is a severe hyperhomocysteinemia and homocystinuria with low plasma methionine.

Patients have neurologic and vascular complications, but no megaloblastic anemia or methylmalonic aciduria.

A

Methylene Tetrahydrofolate Reductase Deficiency

145
Q

The second most common folate disorder

There is a mutation in the gene encoding glutamate formiminotransferase (FTCD), required for the conversion of formiminoglutamate to 5-formiminotetrahydrofolate followed by cyclodeamination of the formimino group forming 5,10-methenyltetrahydrofolate and ammonia

A

Formiminoglutamic Aciduria

146
Q

An autosomal recessive disorder of pyrimidine metabolism characterized by megaloblastic anemia, growth impairment, and excretion of orotic acid in the urine.

A

Hereditary Orotic Aciduria

147
Q

An X-linked disorder of purine metabolism characterized by hyperuricemia, hyperuricosuria, and a neurologic disease with self-mutilation

It is caused by a hypoxanthine-guanine phosphoribosyltransferase deficiency.

A

Lesch-Nyhan Syndrome

148
Q

Children with severe megaloblastic anemia, sensorineural deafness, and non-autoimmune diabetes mellitus, all presenting symptoms in the early childhood or adolescence, have been reported (also known as Rogers syndrome)

The gene for this puzzling disorder has been mapped to the long arm of chromosome 1

A

Thiamine-Responsive Megaloblastic Anemia

149
Q

Types of Congenital Dyserythropoietic Anemia that show megaloblastic red cell precursors

A

Type I usually and type III occasionally

150
Q

Regarded as a manifestation of some sideroblastic anemias and myelodysplastic disorders

Dysplastic features are confined to the erythroid series.

A

Refractory Megaloblastic Anemia

151
Q

Patients at high risk to develop acute megaloblastic anemia

A

Patients transfused extensively during surgery
Patients on dialysis
Patients on TPN

152
Q
A

WILLIAM'S HEMATOLOGY (89 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions