Anemia Flashcards
1
Q
Angina is a symptom of anemia particularly in whom?
A
CAD pts
2
Q
What are the three lab values used in determining RBC mass?
A
- Hb
- HCT
- RBC count
3
Q
Why aren’t Hb, HCT and RBC count perfect measures of anemia?
A
Can be diluted out (they’re concentration dependent)
4
Q
What is the normal range of MCV?
A
80-100 fL
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]
6
Q
What is heme?
A
Fe and protoporphoryin
7
Q
What are the four causes of microcytic anemia?
A
- Fe deficiency
- Anemia of chronic disease
- Sideroblastic anemia
- Thalassemia
8
Q
What is the pathophysiology of sideroblastic anemia?
A
Decrease in the production of the porphoryn ring
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
10
Q
Where does Fe absorption take place in the GI tract?
A
Enterocytes of the duodenum
11
Q
What is the protein that brings in Fe from the gut lumen?
A
DMT1
12
Q
What is the protein channel on enterocytes that transports Fe into the blood, from the enterocyte?
A
Ferroportin
13
Q
True or false: the body has no real way to excrete Fe
A
True
14
Q
What is the regulated step in Fe absorption What is the molecule that regulates this?
A
Ferroportin
Hepcidin
15
Q
What is the protein that transports Fe and delivers it to the liver and bone marrow macrophages?
A
Transferrin
16
Q
What is the protein within cells that stores Fe? Why is this important?
A
Ferritin
Prevent ROS productino
17
Q
What is serum Fe measuring?
A
Actual Fe ions in the blood, even if bound to transferritn
18
Q
What is TIBC measuring?
A
Measures number of transferrin molecules (regardless of if they are bound or not)
19
Q
What is % saturation measuring?
A
% of transferrin molecules bound by Fe
20
Q
What does serum ferritin?
A
How much Fe is present in cells
21
Q
What are the two common causes of adult Fe deficiency anemia? Infants?
A
- Peptic ulcer disease
- Menorrhagia
-Breast feeding in neonates / infants
22
Q
What are the two hookworms that cause anemia?
A
- Ancylostoma duodenale
- Necator americanus
23
Q
What form of Fe is absorbed? (Fe 2+ or Fe 3+)
A
Fe2+ goes into the body
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
25
What are the four stages of Fe deficiency?
1. Storage Fe depleted
2. Serum Fe is depleted
3. Normocytic anemia
4. Microcytic, hypochromic anemia
26
What happens to serum ferritin as the storage Fe is depleted? TIBC?
Serum ferritin goes down
| TIBC goes up
27
What happens to serum iron levels as serum fe is depleted? % saturation?
Both go down
28
What is koilonychia seen in Fe deficiency anemia?
Spoon-shaped nails
29
What happes to the color of RBCs in Fe deficiency anemia?
Hypochromic
30
What happens to RDW with Fe deficiency anemia? Why?
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
31
What does RDW measure?
The variance of RBC size. Thus a high RDW means there is a large variability between each RBC size
32
What happens to free erythrocyte protoporphyrin in the progression of Fe deficiency anemia? Why?
Increases since no Fe to bind to it.
33
***What is the treatment for Fe deficiency anemia?***
Treat underlying cause
Supplemental ferrous sulfate
34
What is Plummer-Vinson syndrome?
Fe deficiency anemia that causes esophageal webs, atrophic glossitis
35
What is anemia of chronic disease? What is the MOA of this?
Anemia associated with chronic inflammation or CA, causing increase in hepcidin
36
What is the role of hepcidin? (3)
- Locks Fe in storage sites
- Prevents uptake of Fe by ferroportin
- Suppresses EPO production
37
What happens to ferritin in anemia of chronic disease? Why?
Increases, since hepcidin prevent the release of Fe from storage
38
What happens to TIBC in anemia of chronic disease? Why?
Decreases since transferrin molecules goes down
39
What happens to serum Fe in anemia of chronic disease? Why?
Decreases since bone marrow takes up to produce RBCs
40
What happens to % saturation in anemia of chronic disease? Why?
Decreases since there is lower Fe to bind to ferritin
41
What happens to FEP in anemia of chronic disease? Why?
Increases since there is no Fe to bind to the porphyrins produced
42
What is the treatment for anemia of chronic disease? (2)
- Treat underlying cause
| - Exogenous EPO
43
What is the enzyme that is involved in the rate limiting step of protoporphyrin production? What is the cofactor for this enzyme?
ALA synthase
Vit B6
44
What is the enzyme that converts ALA to PBG? What is the metal that inhibits this enzyme?
ALA dehydrogenase
Pb
45
What is the enzyme that adds Fe to the protoporphyrin ring? Where does this occur?
Ferrochelatase
In the mitochondria
46
What causes the ringed-sideroblasts seen in sideroblastic anemia?
Fe stored in mitochondria surrounding the nucleus
47
Ringed sideroblasts = what disease?
Sideroblastic anemia
48
What is the blue stain that is used to identify Fe in cells?
Prussian blue
49
Where does the Fe accumulate in sideroblastic anemia?
In mitochondria surrounding nucleus of cells
50
What is the most common cause of sideroblastic anemia?
Defect in the ALA-synthase enzyme
51
What are the three acquired causes of sideroblastic anemia?
- Alcoholism
- Pb poisoning
- Vit B6 deficiency
52
What are the two enzymes that Pb inhibits?
ALA dehydrogenase
| Ferrochelatase
53
What is the drug that causes B6 deficiency, and thus inhibits ALA synthase, causing sideroblastic anemia?
Isoniazid
54
What happens to ferritin in sideroblastic anemia?
Increased
55
What happens to TIBC levels in sideroblastic anemia?
Decrease
56
What happens to Serum Fe in sideroblastic anemia?
increase
57
What happens to % saturation in sideroblastic anemia?
Increases
58
**Sideroblastic anemia labs look identical to what disease?**
**Hemochromatosis**
59
What is the pathophysiology of thalassemia? Is this a macro or microcytic anemia?
Decreased production of Hb chains
Microcytic
60
Thalassemia is beneficial in the prevention of what disease?
Plasmodium falciparum malaria
61
What are the three normal types of Hb found in a human?
HbA
HbA2
HbF
62
What are the globins that comprise HbA?
alpha 2, beta 2
63
What are the globins that comprise Hb A2?
Alpha 2 delta 2
64
What are the globins that comprise HbF?
Alpha 2 gamma 2
65
What chromosome hold the gene for alpha globins? How many are on this chromosome?
- Chromosome 16
| - 4 alleles
66
What is the basis of alpha thalassemia?
Deletion of the alpha gene
67
If 1 alpha gene is deleted, what are the symptoms?
Asymptomatic
68
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?
Mild anemia with increased RBCs
Cis and trans
Cis is worse
69
If 3 alpha genes are deleted, what are the symptoms?
Severe anemia--forms beta-4 tetramers form (HbH) in the absence of sufficient alpha chains
70
Why is the cis deletion of alpha globin genes more severe than the trans?
Cis means on the same chromosome, so more easily passed on to offspring
71
What is HbH? What disease produces this?
Beta4 tetramer, caused by 3 deletions of the alpha globin gene
72
What happens when there are 4 deletion of the alpha globin gene?
gamma4 tetramers form (bart's Hb)
Causes hydrops fetalis and loss in utero
73
What is Bart's Hb, and what is it seen in?
Gamma-4 tetramer, seen in 4x alpha deletion
74
The beta gene is on what chromosome? How many copies are present?
chromosome 11
One per chromosome (=2 total)
75
What is the underlying cause of beta thalassemias? Alpha?
```
Beta = Gene mutations
Alpha = Gene deletions
```
76
What does beta (null) indicated? Beta (+)?
Beta null = no beta chain produced
Beta (+) = some beta chain produced
77
What is the genetic mutation involved in beta thalassemia minor? Symptoms? Findings?
- Beta/beta+
- Asymptomatic
-Microcytic, hypochromic RBCs, and target cells on PBS
78
What are target cells What disease is this seen in?
RBCs that have a bleb in the area of central pallor, causing a target-like appearance.
Seen in beta thalassemia minor
79
What is the key finding in beta thalassemia minor? Why?
Increased HbA2, with a slightly decrease HbA
80
What is the genetic mutation in beta thalassemia major?
Beta null / beta null
81
Does beta thalassemia major present in utero? Why or why not? If not, when does it present?
No, because there is no beta globin in fetal Hbs
Few months later, when demand for HbA increases
82
What is the pathophysiology of hemolysis beta thalassemia major?
Alpha globins pair up to form alpha4, causing extravascular hemolysis
83
What is the massive erythroid hyperplasia seen in beta thalassemia major?
Increase EPO d/t low Hb causes bones (like skull and facial bones) to start to produce Hb
84
Crew cut appearance on x-ray = ?
Beta thalassemia major
85
Chipmunk like facies = ?
Beta thalassemia major
86
Why is there HSM with beta thalassemia major?
Increase EPO causes increased hematopoiesis
87
Why is there a risk of aplastic crisis with parvovirus B19 in pts with beta thalassemia major?
Virus infects erythroid precursors, but beta thalassemia major need every single one of the cells
88
What is the treatment for beta thalassemia? What is the major complication of this?
Chronic transfusions
Secondary Hemochromatosis
89
What is the PBS seen with beta thalassemia major?
- Target cells
- Microcytic, hypochromic
- Nucleated RBCs
90
Target cells
Microcytic, hypochromic
Nucleated RBCs = what disease?
Beta thalassemia major
91
**What are the key electrophoresis findings for beta thalassemia major?**
**Little or no HbA
Increased HbA2 and HbF**
92
What is the most common cause of macrocytic anemia?
Vit B12 or folate deficiency
93
What causes the macrocytosis with macrocytic anemias?
One less cell division occurs
94
What is the major form of THF in the circulation?
N5 methyl THF
95
What reactions does THF participate in?
DNA synthesis
96
What reaction is B12 (methylcobalamin) needed for?
conversion of homocysteine to methionine
97
Why is pernicious anemia a megaloblastic anemia, as opposed to a macrocytic?
Megaloblastic mean that more than one cell type is involved.
Macrocytic means RBCs
98
What is the MOA of increased cell size in pernicious anemia?
Impaired DNA synthesis, causes cells to grow without DNA duplication
99
What happens to PMNs with folate or B12 deficiency?
Hypersegmented--increased number of nuclear lobes (more than 5 diagnostic)
100
What is the difference between megaloblastic anemia and macrocytic anemia?
Multiple lobed nuclei are seen with megaloblastic anemia, but not in macrocytic (only the large RBCs)
101
What are the three common causes of macrocytic anemia, other than a folate/B12 deficiency?
- Alcoholism
- Liver disease
- Drugs
102
What is the antineoplastic drug that can cause macrocytic anemia?
5FU
103
What are the foodstuffs that contain folate? Where is it absorbed in the GI tract?
- green veggies
| - Jejunum
104
Folate deficiency usually develops over what time period?
Months
105
B12 deficiency usually develops over what time period?
Years
106
What is the chemotherapy drug that can cause folate deficiency?
Methotrexate
107
What is the MOA of methotrexate?
Inhibits dihydrofolate reductase
108
What is the classic clinical finding of folate deficiency, beside the s/sx of anemia? Why?
Glossitis--folate is needed for cells in the tongue to turn over.
109
What happens to serum folate in folate deficiency?
Decreases
110
What happens to homocysteine levels in folate deficiency? Why?
Increases
| THF not around to pass methyl group to B12, to convert homocysteine to methionine
111
What happens to methylmalonic acid levels in folate deficiency? B12?
- Normal in folate deficiency
| - Elevated in B12 deficiency
112
What is the protein that binds to B12 in the mouth? What happens once this reaches the duodenum?
- R binder
| - Destruction of the protein by proteases
113
What is the role of intrinsic factor? What cells produce it?
Binds to B12 to increase the absorption of B12
Parietal cells of the stomach
114
Where is B12 absorbed?
Ileum
115
What is the pathogenesis of pernicious anemia?
Autoimmune attack against the parietal cells of the stomach
116
What is the color of the parietal cells of the stomach? What do they do?
- Pink
- Have Proton pumps
- Associated with pernicious anemia
117
What is the color of the gastric cells of the stomach?
Blue
118
What cells in the stomach secrete pepsinogen?
Chief cells
119
Why would a pancreatic insufficiency cause pernicious anemia?
Loss of the proteases that degrade the R binders
120
What is the parasite that loves B12?
Diphyllobothrium latum
121
What is the symptom of pernicious anemia that is not found in folate deficiency?
Degeneration of the spinal cord
122
What happens to serum homocysteine in Vit B12 deficiency?
increases
123
**What happens to serum methylmalonic acid in Vit B12 deficiency?**
**Increases**
124
What are the two major etiologies of normocytic anemia?
- Peripheral destruction
| - underproduction
125
What are reticulocytes? How can you identify them histologically?
Young RBCs--blue on H&E staining d/t increased DNA/RNA
126
What is the normal amount of reticulocytes in the blood?
1% ish
127
Why is it that a decrease in the RBC falsely elevates the percentage of reticulocytes?
Little to no destruction of the reticulocytes, while there is an overall decreases
128
How do you correct reticulocyte count when there is an anemia?
Reticulocyte count x (Hct/45)
129
Greater than what percent of reticulocytes indicates a good marrow response, and suggests peripheral destruction of RBCs?
3%
130
What are globin, heme, and protoporphyrin broken down into by macrophages?
- Globin = amino acids
- Heme = Fe and protoporphyrin
- Protoporphyrin = unconjugated bili
131
How do you differentiate between peripheral destruction of RBCs vs decreased production in normocytic anemia?
Look at reticulocyte count
132
What is extravascular RBC destruction?
Destruction of RBCs by liver spleen etc
133
What is true of both extra and intravascular destruction of RBCs?
Both result in anemia with GOOD marrow response
134
What, generally, is bilirubin? What is this bound to in the serum?
- Breakdown product of protoporphyrin
| - Bound to albumin
135
What happens to the unconjugated bilirubin found in the blood following the destruction of RBCs?
bound to albumin, carried to liver, and excreted via the bile
136
What are the symptoms of hemolysis?
Jaundice
| splenomegaly
137
An increase in unconjugated bili indicates what?
hemolytic anemia
138
An increase in conjugated bili indicates what?
gallbladder obstruction
139
Why is there marrow hyperplasia in hemolytic anemia?
Increased demand for reticulocytes will cause an increase in the cells that produce them
140
What is the protein in the blood that binds free Hb, and brings it back to the liver?
-Haptoglobin
141
What happens to the free haptoglobin levels in intravascular hemolysis? Extravascular?
Intravascular levels will fall
Extravascular levels remain constant
142
What is the cause of the hemoglobinuria in extravascular hemolytic anemia?
Hb Haptocorrin complex will leak out
143
What is the cause of hemosiderinuria in extravascular hemolysis?
Hb goes into tubular cells, and degenerates into hemosiderin. Tubule cells slough off days later.
144
What happens to serum haptoglobin in extravascular hemolysis?
Decreased
145
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
True
146
What are the substrates of ALA synthase?
Succinyl-CoA
| Glycine
147
Cis deletions of alpha gene is more common in which region of the world? Trans?
```
Cis = Asia
Trans = Africa
```
148
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?
Parvovirus B19
ssDNA
Non-enveloped
