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Clinical Medicine 2 > Macrocytic Anemias > Flashcards

Macrocytic Anemias Flashcards

1
Q

What is this describing:
- Deficiency of either folate or cobalamin (B12) with or without other cytopenias, caused by megalobastic hematopoiesis that results from defective DNA synthesis

A

macrocytic anemias

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2
Q

Pertaining to macrocytic anemias:
- RBCs are unusually (…)
- (…) synthesis is defective
- Due to deficiencies in (…) or (…)
- (…) processes occur at a normal rate which results in unequal grown of the (…) and (…)

A
  • large
  • DNA
  • vitamin B12 or folate
  • RNA processes; nucleus and cytoplasm
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3
Q

What are co-enzymes for nuclear maturation and the DNA synthesis pathway?

A

vitamin B12 or folate

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4
Q
  • The most common causes of macrocytic anemias are (…) and (…)
  • What is the MCV in macrocytic anemia?
A
  • vitamin B12 and folate
  • MCV > 100 fL
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5
Q
  • What labs can you order for macrocytic anemias?
  • If all tests are normal, what can you get?
A
  • peripheral smear and retic count; serum vitamin B12, folate, RBC folate levels, methylmalonic acid (MMA) and homocysteine levels; TSH
  • bone marrow biopsy
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6
Q
  • What is the earliest manifestation of megaloblastosis in peripheral blood?
  • What is diagnosed if more than 5% of polymorphonuclear leukocytes have 5 lobes or if 1% have six lobes on the smear?
  • What does this strongly suggest?
A
  • increase in MCV with macro-ovalocytes
  • nuclear hypersegmentation of neutrophils
  • megaloblastosis, especially in association with macro-ovalocytosis
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7
Q
  • Neutrophil hypersegmentation is not sensitive for the diagnosis of (…) and (…) is absent in nearly 50% of cases
  • There may be associated (…) shaped erythrocytes and (…) with leukopenia and thrombocytopenia
A
  • mild cobalamin deficiency; macrocytosis
  • teardrop shaped; anisocytosis
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8
Q

What is the differential diagnosis for megaloblastic macrocytic anemia? (things you need to rule out first)

A
  • vitamine B12 deficiency
  • folic acid deficiency
  • drug-induced
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9
Q

What is the differential diagnosis for non-megaloblastic macrocytic anemia?

A
  • excess alcohol consumption
  • chronic liver disease
  • hypothyroidism
  • aplastic anemia
  • paraproteinemia (multiple myeloma)
  • pregnancy
  • pure red cell aplasia
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10
Q
  • What type of vitamin is vitamin B12?
  • How is it excreted?
  • What is it bound to?
  • What is the name of the B12 found in your blood?
A
  • water soluble vitamin
  • urine
  • plasma proteins
  • cyanocobalamin
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11
Q
  • How do mammals get vitamin B12?
  • Where is it stored?
  • What is the role of vitamin B12?
  • What does vitamin B12 act as a coenzyme for?
A
  • outside source such as diet/supplements because the body cannot synthesize it
  • liver
  • helps synthesize nucleotides, DNA, RNA, and proteins
  • 2 different reactions in the body
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12
Q
  • Vitamin B12 plays a role in (…) of erythroid nucleus
  • Lack of vitamin B12 leads to (…) which is low RBC count specifically due to impaired synthesis of (…)
  • The serum concentration of B12 will be less than (…), the normal levels are (…)
A
  • DNA synthesis
  • macrocytic anemia; RBC DNA
  • 200; 200-900
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13
Q

What are some main causes of B12 deficiency?

A
  • gastric bypass (surgery)
  • bowel diseases (crohns)
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14
Q
  • B12 cannot be absorbed until it reaches the end of the (…)
  • To protect it from being deactivated by enzymes, (…) is made to protect B12 until absorption
  • If a person is deficient in B12, they can lose (…) in nerves which can lead to neurological problems
A
  • small bowel
  • intrinsic factor
  • myelin sheaths
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15
Q

What are extensive possible causes of a cobalamin(B12) deficiency?

A
  • nutritional B12 deficiency (insufficient cobalamin intake)
  • abnormal intragastric events (inadequate breakdown)
  • loss/atrophy of gastric oxyntic mucosa (deficient intrinsic factor)
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16
Q

What patients may have a nutritional cobalamin deficiency?

A
  • vegetarians
  • poverty-imposed-near vegetarians
  • breast-fed infants of mothers with pernicious anemia
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17
Q

What patients may have a cobalamin deficiency due to abnormal intragastric events?

A

patients with:
- atrophic gastritis
- hypochlorhydria (low acid)
- proton pump inhibitors
- H2 blockers

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18
Q

What patients may have a cobalamin deficiency due to deficient intrinstic factor molecules?

A

patients with:
- total or partial gastrectomy
- adult and juvenile pernicious anemia
- caustic destruction (lye)

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19
Q

What are some other causes of cobalamin deficiencies?

A
  • disorders of ileal mucosa/intrinsic factor-cobalamin receptors (IF-cobalamin not bound to IF-cobalamin receptors)
  • diminished or absent cubam receptors (ileal bypass, resection, fistula)
  • drug effects
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20
Q

What are intrinsic factor-cobalamin receptors also known as?

A

cubam receptors

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21
Q

What can cause a decrease or total absence of cubam receptors?

A
  • ileal bypass
  • resection
  • fistula
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22
Q

What drugs can cause cobalamin deficiency?

A
  • metformin
  • cholestyramine
  • colchicine
  • neomycin
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23
Q
  • How long may it take for a patient with a B12 deficiency to show symptoms?
  • Why this long?
  • Humans don’t have to take in that much B12 because we can (…) so there is a baseline
A
  • 3-5 years
  • it is stored for that long in our liver
  • recycle it
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24
Q

What does the aborption process of B12 require?
- a dysfunction in any of these can lead to what?

A
  • intact stomach intrinsic factor
  • pancreatic sufficiency
  • functioning terminal ileum
    can lead to malabsorption
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25
Q

What is the most common cause of macrocytic anemias and is a megaloblastic anemia caused by autoimmune gastritis that impairs intrinsic factor, which is required for vitamin B12 uptake from the gut?

A

pernicious anemia

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26
Q

What can these lead to:
- gastric mucosa attacked by autoimmune disease and destroyed parietal cells that secrete intrinsic factor
- atrophy of gastric mucosa, disordered ileac mucoa

A

pernicious anemia

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27
Q
  • Pernicious anemia may be a (…) or (…) disorder
  • (…) can be formed against instrinsic factor
A
  • congenital or autoimmune
  • autoantibodies
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28
Q

What conditions increase the risk of pernicious anemia?

A
  • past infection with Helicobacter pylori
  • gastrectomy
  • proton-pump inhibitors
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29
Q

In pernicious anemia, gastric galnds in the atrophic mucosa are sparse and consist mainly of (…) cells; the mucosa is densely infiltrated by (…)

A
  • mucus-secreting cells
  • lymphocytes
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30
Q
  • The majority of patients with pernicious anemia are (…)
  • Pernicious anemia is more prevalent in which populations?
A
  • asymptomatic
  • elderly, infants, vegetarians, pregnant and breastfeeding women
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31
Q

What percent of the elderly over age 70 have pernicious anemia and are vitamin B12 deficient?

A

about 6%

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32
Q

Pertaining to risk factors of pernicious anemia:
- There is a heritable component of pernicious anemia; it is deemed congenital if abscence occurs without (…)
- Patients have a higher risk of developing this anemia with a (…) of it
- There is also a strong association of pernicious anemia with (…) and (…) disease

A
  • gastric atrophy
  • family history
  • autoimmune disorders and thyroid disease
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33
Q

What autoimmune disorders are associated with pernicious anemia?

A
  • Addison’s disease
  • type I diabetes
  • vitiligo
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34
Q

What are other factors that increase a patients risk of pernicious anemia?

A
  • gastrectomy, gastric stapling, gastric bypass procedures
  • vegetarianism (especially strict vegans)
  • pharmacologic agents (nitric oxide, metformin, phenformin, colchicine)
35
Q

Perinicious anemia is often unrecognizable in (…) decause of its subtle, slow onset and presentation

A

older adults

36
Q

What are some anemia symptoms of pernicious anemia?

A
  • general weakness/fatigue/light headedness
  • shortness of breath
  • heart palpitations
  • pale skin
  • diarrhea, constipation, loss of appetite
  • swollen, red tongue and/or bleeding gums
37
Q

What are some neurologic symptoms that can occur with prolonged B12 deficiency?

A
  • paresthesia, numbness, muscle weakness, proprioceptive problems
  • degeneration of spinal cord
  • vision loss/changes
  • depression, memory loss, changes in behavior
  • problems concentrating
38
Q

Being deficient in folic acid presents differently that B12 deficiency as it does not affect or cause what?

A

does not affect nerve fibers or cause neurological symptoms

39
Q

What may a peripheral smear of pernicious anemia show?

A
  • hypersegmented neutrophils (> 6)
  • anisocytosis, poikilocytosis
  • macro-ovalocytosis may be present
40
Q

What may a bone marrow aspiration/biopsy in a patient with pernicious anemia show?

(this is not common do to)

A
  • megaloblastric erythroid precursor
  • cells with nuclear cytoplasmic dissociation
41
Q
  • What will serum cobalamin levels be in a patient with pernicious anemia?
  • How will serum LDH and indirect bilirubin be affected (if hemolysis is present)?
  • When doing gastric secretion evals and intrinsic factor antibody assay in a patient with pernicious anemia, what will the results be?
  • What other tests can be done, are highly sensitive but very expensive?
  • How will these tests be affected in cobalamin deficiency?
A
  • < 200 pg/mL (low sensitivity)
  • elevated LDH and indirect bilirubin
  • pernicious anemia; intrinsic factor absent or decreased
  • serum homocysteine and methylmalonic acid (MMA)
  • both will be elevated
42
Q

How will serum homocysteine and methylmalonic acid (MMA) be affected in a cobalamin deficiency vs folate deficiency?

A
  • both will be elevated in cobalamin deficiency
  • only homocysteine will be elevated in folate deficiency
43
Q
  • What is the normal methylmalonic acid (MMA) level?
  • What is the normal total homocysteine levels?
A
  • 70-270 nM
  • 5-14 uM
44
Q

If both methylmalonic acid and total homocysteine are elevated, what is the diagnosis?

A
  • cobalamin deficiency confirmed
  • folate deficiency still possible
    (combined cobalamin + folate deficiency possible)
45
Q

If methylmalonic acid is normal but total homocysteine is elevated, what is the diagnosis?

A
  • folate deficiency likely
  • < 5% may have cobalamin deficiency
46
Q

If both methylmalonic acid and total homocysteine are normal, what is the diagnosis relating to cobalamin/folate deficiencies?

A

both cobalamin and folate deficiencies are excluded

47
Q

What is the treatment for pernicious anemia in severely decompensated patients (emergent)?

A
  • transfusion post blood draw
  • vitamin replacement
48
Q

What is the treatment for individuals with an established cobalamin deficiency?

A
  • replace B12 rapidly at 1 mg/day IM or SQ (1st week), 1 mg twice weekly (2nd week), 1 mg/week (3rd-6th week), 1 mg/month (for life)
  • pernicious anemia - lifelong 1 mg/month

(treatment the same no matter the cause)

49
Q

What is the treatment for individuals with a mild cobalamin deficiency?

A

oral cobalamin (sublingual) 2 mg/day for 3 months, then monthly maintenance or 2 mg/day orally

(food intake will reduce absorption of oral by 50%)

50
Q

What is the treatment for a patient with a subclinical deficiency of B12? How does this patient typically present?

A
  • patient asymptomatic w/ mildly abnormal values for many months but sometimes returns to normal
  • no treatment and level monitoring
  • monitor and treat when levels are abnormal
  • empiric treatment 1-2 mg/day orally while monitoring levels every 6-12 months
51
Q

Neurological signs and symptoms of cobalamin deficiency are reversible if treated within (…)

A

6 months

52
Q
  • Folate is an essential vitamin for (…) and (…) synthesis
  • Where does absorption of folate occur?
  • Is folate dependent on any other facilitating factors?
  • Folate deficiencies are common in which individuals?
  • What is a folate deficiency associated with in the fetus?
A
  • RNA and DNA synthesis
  • upper small intestion
  • no
  • alcoholics, chronic malnourishment
  • neural tube defects
53
Q
  • Folic acid is required for (…) and (…) synthesis, however, it must come from (…) sources
  • Daily needs of folic acid are dependent on what?
  • The degree of absorption depends on its (…)
  • About (…) of folate naturally occurring in food is bioavailable
  • Folate is (…) in fruits and veggies, but boiling veggies destroys (…)% of folate content
  • (…)% of folic acid supplementation is bioavailable when consumed with food
A
  • DNA and RNA; exogenous
  • age and other co-morbidities
  • source
  • half
  • endogenous; 95%
  • 85%
54
Q

Where is folate stored?
How is it excreted?

A
  • fat tissue and the liver
  • urine and bile
55
Q

Pertaining to folate deficiency:
- can lead to (…) anemia
- can lead to (…) defects in utero
- will result in impairment in (…) and accumulation of (…)
- is associated with (…) levels of homocysteine with chronic deficiency
- is associated with an increased risk for (…) and (…)

A
  • megaloblastic anemia
  • neural tube defects
  • cell division; toxic metabolites
  • elevated levels
  • ischemic heart disease and stroke
56
Q

What are some causes of folate deficiencies?

(longer list)

A
  • nutritional causes
  • decreased dietary intake d/t poverty/famine, institutionalization, debilitating disease, feeding infants w/ goats milk
  • decreased dietary intake with increased requirements (pregnancy/lactation)
  • pregnancy, lactation, prematurity, hyperemesis gravidarum, infancy
  • folate antagonists
  • drugs
57
Q

What can lead to folate deficiency?

A
  • deficieny folic acid consumption
  • previous diagnosis of hemolytic anemia
  • alcoholism
  • medications
58
Q

What is the RDA of folic acid consumption for:
- adult men and non-pregnant women
- pregnant women
- lactating women
- children between 9-18 years old

A
  • 400 ug
  • 600 ug
  • 500 ug
  • 300-400 ug
59
Q

Why can alcoholism lead to a folate deficiency?

A
  • hyperactive alcohol dehydrogenase can catabolize folate prior to its absorption in the gut
60
Q

What medications can cause folate deficiency?

A
  • folate antagonists: phenytoin, methotrexate, TMP-SMX, sulfasalazine
  • triamterene, pyrimethamine, barbiturates
61
Q
  • Symptoms of anemia manifests within (…) of folate deficiency and dominates the overall clinical picture
  • What are some general symptoms of anemia in this case?
A
  • 4-6 months
  • weakness, pallor, dizziness, fatigue
62
Q

What are some more specific symptoms specific to folate deficiency (hematologic/mouth)?

A

hematologic:
- pancytopenia w/ megaloblastic bone marrow
mouth:
- sore/swollen/red tongue or dysphagia (glossitis)
- mouth ulcers
- angular cheilosis

63
Q

What are some gastrointestinal manifestations of folate deficiency?

A
  • megaloblastosis w or w/o malabsorption
  • vomiting, abdominal pain, diarrhea especially after meals
  • anorexia or marked weight loss
64
Q

What are some dermatologic manifestarions of folate deficiency?

A
  • acquired hyperpigmentation of skin on palms and soles
  • overall gross pallor
  • premature graying
65
Q

What are some other manifestations of folate deficiency?

(2)

A
  • infertility
  • psychiatric: flat affect
66
Q
  • When a patient comes in with macrocytic anemia (suspected folate deficiency), what should done first?
  • After determining folate deficiency, what can be ordered?
  • What reflects changes in folate intake?
  • What test should be ordered next?
  • What makes this test unreliable?
A
  • rule out cobalamin (B12) deficiency by obtaining serum cobalamin level
  • serum folate level
  • serume folate
  • RBC folate level
  • RBC transfusions
67
Q
  • What is the normal range of serum cobalamin?
  • Folate treatment will not be effective on neurological symptoms if (…) is the cause
  • What levels alone are not enough to diagnose a folate deficiency as 2-5% of the population are naturally deficient and considered normal?
  • What test is only useful in ruling out folate deficiency ( > 5 ng/mL is the target to r/o)
  • What test level reflects folate storage levels?
  • If this test is low, then it is (…)
A
  • 200-900 pg/mL
  • cobalamin
  • serum folate
  • serum folate
  • RBC folate levels
  • diagnostic of folate deficiency
68
Q

What is the pattern for work-ups when determining folate deficiency?

A
  • serum cobalamin
  • serum folate
  • RBC folate level
  • serum homocysteine, methylmalonic acid
  • peripheral smear
69
Q
  • What will be elevated in both folate deficiency and B12 deficiency?
  • What is only elevated in B12 deficiency only?
  • If this is not elevated, then it is most likely (…)
A
  • serum homocysteine level
  • serum methylmalonic acid (MMA)
  • folate deficiency
70
Q

What will be seen on a peripheral smear for a patient with folate deficiency?

A
  • hypersegmented neutrophils and oval macrocytes
  • howell-jolly bodies (nuclear remnants) are typical
71
Q

What is pathognomonic for folate deficiency if seen on a peripheral smear?

A

hypersegmented neutrophils and oval macrocytes

72
Q
  • What tests help guide diagnosis and treatment of folate deficiency?
  • What tests are the most diagnostic for folate deficiency?
A
  • folate and cobalamin levels
  • serum homocystein and methylmalonic acid levels
73
Q

What is the dialy requirement of folate that is usually met by balanced diet?

A

50-100 mg/dL

74
Q

What is the treatment for acute and chronic folate deficiency?

A
  • 1 mg/day or IV until complete hematologic recovery documented
    ** adequate absorption despite intestinal malabsorption
75
Q

What are some other methods of treating folate deficiencies?

A
  • increase folate through dietary changes
  • supplemental dietary folic acid during pregnancy
76
Q

What are some foods that you can obtain folate through? What should you avoid?

A
  • leafy green veggies, fruits, eggs, poultry, pork, fortified cereals
  • avoid alcohol and antagonists
77
Q

What should be given during pregnancy that can reduce incidence of neural tube defects in babies is mom is folate deficient?

A

supplemental dietary folic acid

78
Q
  • Folate deficiencies will not manifest with (…)
  • Be sure to ask patients if they have had (…)
A
  • neurologic symptoms such as neuropathy
  • peripheral neuropathy
79
Q

You can narrow down your diagnosis of folate deficiency anemia by considering what?

A
  • alcoholics
  • pregnancy
  • gluten-free diet
  • methotrexate use (antagonist)
80
Q

What are some causes of megaloblastic anemia not responding to therapy with cobalamin or folate?

A
  • wrong diagnosis
  • combined folate and cobalamin deficiencies treated with only one vitamin
  • associated iron deficiency
  • associated hemoglobinopathy (sickle cell, thalassemia)
  • associated ACD
  • associated hypothyroidism
81
Q

What is this showing? What is this associated with?

A
  • hypersegmentation
  • pernicious anemia (possibly folate deficiency)
82
Q

What is this showing? What is this associated wtih?

A
  • hypersegmentation with oval macrocytes
  • folate deficiency
83
Q

What is this showing? These are typically seen on a peripheral smear associated with what?

A
  • howell-jolly bodies
  • folate deficiency

Clinical Medicine 2 (9 decks)

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