Anemia Flashcards

1
Q

Angina is a symptom of anemia particularly in whom?

A

CAD pts

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2
Q

What are the three lab values used in determining RBC mass?

A
  • Hb
  • HCT
  • RBC count
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3
Q

Why aren’t Hb, HCT and RBC count perfect measures of anemia?

A

Can be diluted out (they’re concentration dependent)

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4
Q

What is the normal range of MCV?

A

80-100 fL

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5
Q

What is the direct cause of microcytosis? Why does this occur?

A

Extra division of progenitor RBCs in an attempt to maintain the same [Hb]

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6
Q

What is heme?

A

Fe and protoporphoryin

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7
Q

What are the four causes of microcytic anemia?

A
  1. Fe deficiency
  2. Anemia of chronic disease
  3. Sideroblastic anemia
  4. Thalassemia
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8
Q

What is the pathophysiology of sideroblastic anemia?

A

Decrease in the production of the porphoryn ring

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9
Q

What are the two forms of dietary Fe? Which is more readily absorbed?

A

heme and nonheme

Heme form is more readily absorbed

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10
Q

Where does Fe absorption take place in the GI tract?

A

Enterocytes of the duodenum

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11
Q

What is the protein that brings in Fe from the gut lumen?

A

DMT1

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12
Q

What is the protein channel on enterocytes that transports Fe into the blood, from the enterocyte?

A

Ferroportin

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13
Q

True or false: the body has no real way to excrete Fe

A

True

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14
Q

What is the regulated step in Fe absorption What is the molecule that regulates this?

A

Ferroportin

Hepcidin

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15
Q

What is the protein that transports Fe and delivers it to the liver and bone marrow macrophages?

A

Transferrin

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16
Q

What is the protein within cells that stores Fe? Why is this important?

A

Ferritin

Prevent ROS productino

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17
Q

What is serum Fe measuring?

A

Actual Fe ions in the blood, even if bound to transferritn

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18
Q

What is TIBC measuring?

A

Measures number of transferrin molecules (regardless of if they are bound or not)

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19
Q

What is % saturation measuring?

A

% of transferrin molecules bound by Fe

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20
Q

What does serum ferritin?

A

How much Fe is present in cells

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21
Q

What are the two common causes of adult Fe deficiency anemia? Infants?

A
  • Peptic ulcer disease
  • Menorrhagia

-Breast feeding in neonates / infants

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22
Q

What are the two hookworms that cause anemia?

A
  • Ancylostoma duodenale

- Necator americanus

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23
Q

What form of Fe is absorbed? (Fe 2+ or Fe 3+)

A

Fe2+ goes into the body

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24
Q

What is the role of acid and Fe absorption? How does a gastrectomy affect this?

A

Maintains the Fe2 + state, which is more readily absorbed

Gastrectomy will cause a decrease in acid production

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25
Q

What are the four stages of Fe deficiency?

A
  1. Storage Fe depleted
  2. Serum Fe is depleted
  3. Normocytic anemia
  4. Microcytic, hypochromic anemia
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26
Q

What happens to serum ferritin as the storage Fe is depleted? TIBC?

A

Serum ferritin goes down

TIBC goes up

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27
Q

What happens to serum iron levels as serum fe is depleted? % saturation?

A

Both go down

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28
Q

What is koilonychia seen in Fe deficiency anemia?

A

Spoon-shaped nails

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29
Q

What happes to the color of RBCs in Fe deficiency anemia?

A

Hypochromic

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30
Q

What happens to RDW with Fe deficiency anemia? Why?

A

Increases

Because bone marrow still trying to produce normal RBCs, but is getting to the point where it no longer can d/t demand for oxygen

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31
Q

What does RDW measure?

A

The variance of RBC size. Thus a high RDW means there is a large variability between each RBC size

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32
Q

What happens to free erythrocyte protoporphyrin in the progression of Fe deficiency anemia? Why?

A

Increases since no Fe to bind to it.

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33
Q

What is the treatment for Fe deficiency anemia?

A

Treat underlying cause

Supplemental ferrous sulfate

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34
Q

What is Plummer-Vinson syndrome?

A

Fe deficiency anemia that causes esophageal webs, atrophic glossitis

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35
Q

What is anemia of chronic disease? What is the MOA of this?

A

Anemia associated with chronic inflammation or CA, causing increase in hepcidin

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36
Q

What is the role of hepcidin? (3)

A
  • Locks Fe in storage sites
  • Prevents uptake of Fe by ferroportin
  • Suppresses EPO production
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37
Q

What happens to ferritin in anemia of chronic disease? Why?

A

Increases, since hepcidin prevent the release of Fe from storage

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38
Q

What happens to TIBC in anemia of chronic disease? Why?

A

Decreases since transferrin molecules goes down

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39
Q

What happens to serum Fe in anemia of chronic disease? Why?

A

Decreases since bone marrow takes up to produce RBCs

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40
Q

What happens to % saturation in anemia of chronic disease? Why?

A

Decreases since there is lower Fe to bind to ferritin

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41
Q

What happens to FEP in anemia of chronic disease? Why?

A

Increases since there is no Fe to bind to the porphyrins produced

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42
Q

What is the treatment for anemia of chronic disease? (2)

A
  • Treat underlying cause

- Exogenous EPO

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43
Q

What is the enzyme that is involved in the rate limiting step of protoporphyrin production? What is the cofactor for this enzyme?

A

ALA synthase

Vit B6

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44
Q

What is the enzyme that converts ALA to PBG? What is the metal that inhibits this enzyme?

A

ALA dehydrogenase

Pb

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45
Q

What is the enzyme that adds Fe to the protoporphyrin ring? Where does this occur?

A

Ferrochelatase

In the mitochondria

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46
Q

What causes the ringed-sideroblasts seen in sideroblastic anemia?

A

Fe stored in mitochondria surrounding the nucleus

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47
Q

Ringed sideroblasts = what disease?

A

Sideroblastic anemia

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48
Q

What is the blue stain that is used to identify Fe in cells?

A

Prussian blue

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49
Q

Where does the Fe accumulate in sideroblastic anemia?

A

In mitochondria surrounding nucleus of cells

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50
Q

What is the most common cause of sideroblastic anemia?

A

Defect in the ALA-synthase enzyme

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51
Q

What are the three acquired causes of sideroblastic anemia?

A
  • Alcoholism
  • Pb poisoning
  • Vit B6 deficiency
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52
Q

What are the two enzymes that Pb inhibits?

A

ALA dehydrogenase

Ferrochelatase

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53
Q

What is the drug that causes B6 deficiency, and thus inhibits ALA synthase, causing sideroblastic anemia?

A

Isoniazid

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54
Q

What happens to ferritin in sideroblastic anemia?

A

Increased

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55
Q

What happens to TIBC levels in sideroblastic anemia?

A

Decrease

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56
Q

What happens to Serum Fe in sideroblastic anemia?

A

increase

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57
Q

What happens to % saturation in sideroblastic anemia?

A

Increases

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58
Q

Sideroblastic anemia labs look identical to what disease?

A

Hemochromatosis

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59
Q

What is the pathophysiology of thalassemia? Is this a macro or microcytic anemia?

A

Decreased production of Hb chains

Microcytic

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60
Q

Thalassemia is beneficial in the prevention of what disease?

A

Plasmodium falciparum malaria

61
Q

What are the three normal types of Hb found in a human?

A

HbA
HbA2
HbF

62
Q

What are the globins that comprise HbA?

A

alpha 2, beta 2

63
Q

What are the globins that comprise Hb A2?

A

Alpha 2 delta 2

64
Q

What are the globins that comprise HbF?

A

Alpha 2 gamma 2

65
Q

What chromosome hold the gene for alpha globins? How many are on this chromosome?

A
  • Chromosome 16

- 4 alleles

66
Q

What is the basis of alpha thalassemia?

A

Deletion of the alpha gene

67
Q

If 1 alpha gene is deleted, what are the symptoms?

A

Asymptomatic

68
Q

If 2 alpha genes are deleted, what are the symptoms? What are the two deletion types that can occur to cause this (since there are 4 genes)? Which is worse?

A

Mild anemia with increased RBCs

Cis and trans

Cis is worse

69
Q

If 3 alpha genes are deleted, what are the symptoms?

A

Severe anemia–forms beta-4 tetramers form (HbH) in the absence of sufficient alpha chains

70
Q

Why is the cis deletion of alpha globin genes more severe than the trans?

A

Cis means on the same chromosome, so more easily passed on to offspring

71
Q

What is HbH? What disease produces this?

A

Beta4 tetramer, caused by 3 deletions of the alpha globin gene

72
Q

What happens when there are 4 deletion of the alpha globin gene?

A

gamma4 tetramers form (bart’s Hb)

Causes hydrops fetalis and loss in utero

73
Q

What is Bart’s Hb, and what is it seen in?

A

Gamma-4 tetramer, seen in 4x alpha deletion

74
Q

The beta gene is on what chromosome? How many copies are present?

A

chromosome 11

One per chromosome (=2 total)

75
Q

What is the underlying cause of beta thalassemias? Alpha?

A
Beta = Gene mutations
Alpha = Gene deletions
76
Q

What does beta (null) indicated? Beta (+)?

A

Beta null = no beta chain produced

Beta (+) = some beta chain produced

77
Q

What is the genetic mutation involved in beta thalassemia minor? Symptoms? Findings?

A
  • Beta/beta+
  • Asymptomatic

-Microcytic, hypochromic RBCs, and target cells on PBS

78
Q

What are target cells What disease is this seen in?

A

RBCs that have a bleb in the area of central pallor, causing a target-like appearance.

Seen in beta thalassemia minor

79
Q

What is the key finding in beta thalassemia minor? Why?

A

Increased HbA2, with a slightly decrease HbA

80
Q

What is the genetic mutation in beta thalassemia major?

A

Beta null / beta null

81
Q

Does beta thalassemia major present in utero? Why or why not? If not, when does it present?

A

No, because there is no beta globin in fetal Hbs

Few months later, when demand for HbA increases

82
Q

What is the pathophysiology of hemolysis beta thalassemia major?

A

Alpha globins pair up to form alpha4, causing extravascular hemolysis

83
Q

What is the massive erythroid hyperplasia seen in beta thalassemia major?

A

Increase EPO d/t low Hb causes bones (like skull and facial bones) to start to produce Hb

84
Q

Crew cut appearance on x-ray = ?

A

Beta thalassemia major

85
Q

Chipmunk like facies = ?

A

Beta thalassemia major

86
Q

Why is there HSM with beta thalassemia major?

A

Increase EPO causes increased hematopoiesis

87
Q

Why is there a risk of aplastic crisis with parvovirus B19 in pts with beta thalassemia major?

A

Virus infects erythroid precursors, but beta thalassemia major need every single one of the cells

88
Q

What is the treatment for beta thalassemia? What is the major complication of this?

A

Chronic transfusions

Secondary Hemochromatosis

89
Q

What is the PBS seen with beta thalassemia major?

A
  • Target cells
  • Microcytic, hypochromic
  • Nucleated RBCs
90
Q

Target cells
Microcytic, hypochromic

Nucleated RBCs = what disease?

A

Beta thalassemia major

91
Q

What are the key electrophoresis findings for beta thalassemia major?

A

**Little or no HbA

Increased HbA2 and HbF**

92
Q

What is the most common cause of macrocytic anemia?

A

Vit B12 or folate deficiency

93
Q

What causes the macrocytosis with macrocytic anemias?

A

One less cell division occurs

94
Q

What is the major form of THF in the circulation?

A

N5 methyl THF

95
Q

What reactions does THF participate in?

A

DNA synthesis

96
Q

What reaction is B12 (methylcobalamin) needed for?

A

conversion of homocysteine to methionine

97
Q

Why is pernicious anemia a megaloblastic anemia, as opposed to a macrocytic?

A

Megaloblastic mean that more than one cell type is involved.

Macrocytic means RBCs

98
Q

What is the MOA of increased cell size in pernicious anemia?

A

Impaired DNA synthesis, causes cells to grow without DNA duplication

99
Q

What happens to PMNs with folate or B12 deficiency?

A

Hypersegmented–increased number of nuclear lobes (more than 5 diagnostic)

100
Q

What is the difference between megaloblastic anemia and macrocytic anemia?

A

Multiple lobed nuclei are seen with megaloblastic anemia, but not in macrocytic (only the large RBCs)

101
Q

What are the three common causes of macrocytic anemia, other than a folate/B12 deficiency?

A
  • Alcoholism
  • Liver disease
  • Drugs
102
Q

What is the antineoplastic drug that can cause macrocytic anemia?

A

5FU

103
Q

What are the foodstuffs that contain folate? Where is it absorbed in the GI tract?

A
  • green veggies

- Jejunum

104
Q

Folate deficiency usually develops over what time period?

A

Months

105
Q

B12 deficiency usually develops over what time period?

A

Years

106
Q

What is the chemotherapy drug that can cause folate deficiency?

A

Methotrexate

107
Q

What is the MOA of methotrexate?

A

Inhibits dihydrofolate reductase

108
Q

What is the classic clinical finding of folate deficiency, beside the s/sx of anemia? Why?

A

Glossitis–folate is needed for cells in the tongue to turn over.

109
Q

What happens to serum folate in folate deficiency?

A

Decreases

110
Q

What happens to homocysteine levels in folate deficiency? Why?

A

Increases

THF not around to pass methyl group to B12, to convert homocysteine to methionine

111
Q

What happens to methylmalonic acid levels in folate deficiency? B12?

A
  • Normal in folate deficiency

- Elevated in B12 deficiency

112
Q

What is the protein that binds to B12 in the mouth? What happens once this reaches the duodenum?

A
  • R binder

- Destruction of the protein by proteases

113
Q

What is the role of intrinsic factor? What cells produce it?

A

Binds to B12 to increase the absorption of B12

Parietal cells of the stomach

114
Q

Where is B12 absorbed?

A

Ileum

115
Q

What is the pathogenesis of pernicious anemia?

A

Autoimmune attack against the parietal cells of the stomach

116
Q

What is the color of the parietal cells of the stomach? What do they do?

A
  • Pink
  • Have Proton pumps
  • Associated with pernicious anemia
117
Q

What is the color of the gastric cells of the stomach?

A

Blue

118
Q

What cells in the stomach secrete pepsinogen?

A

Chief cells

119
Q

Why would a pancreatic insufficiency cause pernicious anemia?

A

Loss of the proteases that degrade the R binders

120
Q

What is the parasite that loves B12?

A

Diphyllobothrium latum

121
Q

What is the symptom of pernicious anemia that is not found in folate deficiency?

A

Degeneration of the spinal cord

122
Q

What happens to serum homocysteine in Vit B12 deficiency?

A

increases

123
Q

What happens to serum methylmalonic acid in Vit B12 deficiency?

A

Increases

124
Q

What are the two major etiologies of normocytic anemia?

A
  • Peripheral destruction

- underproduction

125
Q

What are reticulocytes? How can you identify them histologically?

A

Young RBCs–blue on H&E staining d/t increased DNA/RNA

126
Q

What is the normal amount of reticulocytes in the blood?

A

1% ish

127
Q

Why is it that a decrease in the RBC falsely elevates the percentage of reticulocytes?

A

Little to no destruction of the reticulocytes, while there is an overall decreases

128
Q

How do you correct reticulocyte count when there is an anemia?

A

Reticulocyte count x (Hct/45)

129
Q

Greater than what percent of reticulocytes indicates a good marrow response, and suggests peripheral destruction of RBCs?

A

3%

130
Q

What are globin, heme, and protoporphyrin broken down into by macrophages?

A
  • Globin = amino acids
  • Heme = Fe and protoporphyrin
  • Protoporphyrin = unconjugated bili
131
Q

How do you differentiate between peripheral destruction of RBCs vs decreased production in normocytic anemia?

A

Look at reticulocyte count

132
Q

What is extravascular RBC destruction?

A

Destruction of RBCs by liver spleen etc

133
Q

What is true of both extra and intravascular destruction of RBCs?

A

Both result in anemia with GOOD marrow response

134
Q

What, generally, is bilirubin? What is this bound to in the serum?

A
  • Breakdown product of protoporphyrin

- Bound to albumin

135
Q

What happens to the unconjugated bilirubin found in the blood following the destruction of RBCs?

A

bound to albumin, carried to liver, and excreted via the bile

136
Q

What are the symptoms of hemolysis?

A

Jaundice

splenomegaly

137
Q

An increase in unconjugated bili indicates what?

A

hemolytic anemia

138
Q

An increase in conjugated bili indicates what?

A

gallbladder obstruction

139
Q

Why is there marrow hyperplasia in hemolytic anemia?

A

Increased demand for reticulocytes will cause an increase in the cells that produce them

140
Q

What is the protein in the blood that binds free Hb, and brings it back to the liver?

A

-Haptoglobin

141
Q

What happens to the free haptoglobin levels in intravascular hemolysis? Extravascular?

A

Intravascular levels will fall

Extravascular levels remain constant

142
Q

What is the cause of the hemoglobinuria in extravascular hemolytic anemia?

A

Hb Haptocorrin complex will leak out

143
Q

What is the cause of hemosiderinuria in extravascular hemolysis?

A

Hb goes into tubular cells, and degenerates into hemosiderin. Tubule cells slough off days later.

144
Q

What happens to serum haptoglobin in extravascular hemolysis?

A

Decreased

145
Q

True or false: the bone marrow will produce a normocytic anemia in the beginning stages of Fe deficiency anemia, prior to progressing to a microcytic anemia

A

True

146
Q

What are the substrates of ALA synthase?

A

Succinyl-CoA

Glycine

147
Q

Cis deletions of alpha gene is more common in which region of the world? Trans?

A
Cis = Asia
Trans = Africa
148
Q

What is the virus that can cause an aplastic crisis in beta thalassemia major pts? What is the genetic makeup and enveloped status of this?

A

Parvovirus B19
ssDNA
Non-enveloped