Anemias- Lecture Flashcards
(117 cards)
1
Q
A
Purple blotches in the background that look like dirt are platelets
2
Q
What does hematocrit (Hct) represent?
A
Hematocrit (Hct) is the percentage of blood composed of RBCs
3
Q
MCH vs MCHC
A
Mean cell hemoglobin (MCH) is the average weight of hemoglobin per RBC
Mean cell hemoglobin concentration (MCHC) is the average concentration of hemoglobin per RBC
4
Q
Relative erythrocytosis occurs due to _
Absolute erythrocytosis occurs due to _
A
Relative erythrocytosis occurs due to decreased plasma volume
Absolute erythrocytosis occurs due to increased RBC mass
5
Q
(True/ False) Anemia is a decrease in red blood cell mass
A
True; this comes with decreased oxygen and carbon dioxide transport
6
Q
(True/ False) All anemias will have decreased hemoglobin, hematocrit, and RBC count
A
True; All anemias will have decreased hemoglobin, hematocrit, and RBC count
7
Q
Normal sized RBCs are _
Large RBCs are _
Small RBCs are _
A
Normal sized RBCs are normocytic
Large RBCs are macrocytic
Small RBCs are microcytic
8
Q
Anisocytosis
A
Anisocytosis means the RBCs vary in size
9
Q
If RBCs vary in shape we call this _
A
If RBCs vary in shape we call this poikilocytosis
10
Q
“Normochromic, hypochromic, and hyperchromic” reflect the amount of _ and is measured with _ or _
A
“Normochromic, hypochromic, and hyperchromic” reflects the amount of hemoglobin and is measured with MCH or MCHC
11
Q
Classify as normocytic, microcytic, or macrocytic
A
Normocytic: normal RBCs are the size of a lymphocyte nucleus
12
Q
When might you see the following?
A
Acanthocyte (spur cell): seen with liver disease
13
Q
When might you see the following?
A
Bite cell: seen in G6PD deficiency
14
Q
When might you see the following?
A
Target cell (aka codocyte): thalassemia
15
Q
When might you see the following?
A
Echinocyte (burr cell): kidney disease
16
Q
When might you see the following?
A
Schistocyte: microangiopathic hemolytic anemia
17
Q
When might you see the following?
A
Sickle cell: sickle cell anemia
18
Q
When might you see the following?
A
Spherocyte: either warm autoimmune hemolytic anemia or hereditary spherocytosis
19
Q
_ are younger RBCs that have not yet ejected all of their genetic material
A
Reticulocytes are younger RBCs that have not yet ejected all of their genetic material
* They are visualized using a supravital stain
20
Q
Supravital stain (for reticulocyte count) will highlight _
A
Supravital stain (for reticulocyte count) will highlight rRNA
* Uses crystal violet and brilliant cresyl blue
21
Q
How can the reticulocyte count be interpreted?
A
Increased reticulocyte: bone marrow is responding to the anemia
Normal or decreased reticulocyte: bone marrow is not responding to anemia (hypoproliferative anemia)
22
Q
What are the general symptoms of anemia?
A
- Dyspnea (short of breath)
- Fatigue
- Dizziness
- Tachycardia
- Conjunctival pallor
23
Q
Jaundice is a sx that is exclusive to _ anemias
A
Jaundice is a sx that is exclusive to hemolytic anemias
24
Q
Megaloblastic anemia falls into the (decreased production/ increased destruction) category
A
Megaloblastic anemia falls into the decreased production category
25
Sideroblastic anemia falls into the (decreased production/ increased destruction) category
Sideroblastic anemia falls into the **decreased production** category
26
Name the 3 microcytic anemias
1. Iron-deficiency anemia
2. Thalassemia
3. Sideroblastic anemia
27
Name the two macrocytic anemias
1. Megaloblastic anemia
2. Nonmegaloblastic anemia (alcohol related)
28
Megaloblastic anemias result from decreased RBC production due to the missing _ which is caused by a deficiency in _ or _
**Megaloblastic anemias** result from decreased RBC production due to the missing **building blocks of DNA synthesis** which is caused by a deficiency in **folate (B9)** or **vitamin B12**
29
Megaloblastic anemia can be caused by medications like _ , _ , _
Megaloblastic anemia can be caused by medications like **chemo** , **anti-retroviral drugs** , **hydroxyurea**
30
Cells in our bone marrow rapidly turn over --> this means they require a lot of _ and _ to constantly synthesize DNA
Cells in our bone marrow rapidly turn over --> this means they require a lot of **folate** and **B12** to constantly synthesize DNA
* *A deficiency in these will decrease cell division*
31
Megaloblastoid changes occur in the bone marrow including cytoplasmic assynchrony, which means _
Megaloblastoid changes occur in the bone marrow including cytoplasmic assynchrony, which means **cytoplasm continues to grow while the nucleus is stunted** --> ineffective erythropoiesis
32
To get from homocysteine --> methionine we need THF to _ and we need the presence of _
To get from **homocysteine --> methionine --> DNA** we need THF to **donate a methyl group** and we need the presence of **B12 and folate**
33
Methylmalonyl CoA --> Succinyl CoA --> myelin requires only _
Methylmalonyl CoA --> Succinyl CoA --> myelin requires only **B12**
* Therefore only B12 deficiency is associated with neuro deficits
34
B12 deficiency will result in an accumulation of _
B12 deficiency will result in an accumulation of **homocysteine** and **methylmalonic acid**
35
Folate deficiency will result in an accumulation of _
Folate deficiency will result in an accumulation of **homocysteine** only
36
Vitamin B12 gets absorbed in the _
Vitamin B12 gets absorbed in the **ileum** (last part of the small intestine)
* Needs to be bound to intrinsic factor (IF)
37
_ occurs when there is a lack of intrinsic factor which inhibits the absorption of B12 in the small intestine and leads to megaloblastic anemia
**Pernicious anemia** occurs when there is a lack of intrinsic factor which inhibits the absorption of B12 in the small intestine and leads to megaloblastic anemia
* Begins with auto-antibodies destroying gastric parietal cells
38
Three causes of vitamin B12 AND folate deficiency
1. **Intestinal malabsorption** (example crohn's disease affects the terminal ileum and celiacs affects the duodenum)
2. **Alcohol** (general lack of nutrients)
3. **Diet** (poor diet)
39
What is non-megaloblastic anemia?
**Non-megaloblastic anemia** is a macrocytic anemia without B12 or folate deficiency
* Causes: liver disease, medications, hypothyroidism, copper deficiency
40
Vitamin B12 in our diet comes from sources like _
**Vitamin B12** in our diet comes from sources like **animal liver, meat, fish, cheese, dairy, eggs**
41
Folate in our diet comes from _
Folate in our diet comes from **dark leafy green vegetables**
42
How long does it take to deplete our stores of vitamin B12 vs. folate?
**Vitamin B12**: stored in the liver; **takes months-years to deplete**
* Strict vegans can eventually become deficient
**Folate**: takes months to deplete
43
Name 5 causes specific to B12 deficiency
1. Pernicious anemia
2. Pancreatic insufficiency
3. Medications
4. Diphyllobotrium latum
5. Surgically absent ileum
44
How does pancreatic insufficiency lead to B12 deficiencies?
**Trypsin** (enzyme produced in the pancreas) is needed to **cleave transcobalamin and release B12**
45
_ is a fish tapeworm that is known to cause vitamin B12 deficiency leading to megaloblastic anemia
***Diphyllobotrium latum*** is a fish tapeworm that is known to cause vitamin B12 deficiency leading to megaloblastic anemia
46
What are 3 causes specific to folate deficiency?
1. **Rapid cell turnover states** (pregnancy, cancer)
2. **Medications**
3. **Gastric bypass surgery** (shortened jejunum)
47
What is the consequence of low folate during pregnancy?
Low birth weight infants
Neural tube defects
48
_ and _ are antimetabolite drugs which inhibit the conversion of folate to its active form
**Trimethoprim (TMP)** and **Methotrexate** are antimetabolite drugs which inhibit the conversion of folate to its active form
49
_ is an anti-epileptic drug that inhibits folate absorption in the duodenum
**Phenytoin** is an anti-epileptic drug that inhibits folate absorption in the duodenum
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Megaloblastic anemias can be diagnosed by the presence of _ or _ on peripheral blood smear
Megaloblastic anemias can be diagnosed by the presence of **macrocytic erythrocytes** or **hypersegmented neutrophils** on peripheral blood smear
51
Megaloblastic anemia can be diagnosed on a bone marrow biopsy by the presence of _
Megaloblastic anemia can be diagnosed on a bone marrow biopsy by the presence of **immature-appearing nuclei with mature cytoplasm**
52
B12 deficiencies present with unique sx of _ and _
B12 deficiencies present with unique sx of **glossitis** and **neuropsychiatric findings**
* Degeneration of spinal cord
* Sensory deficits, ataxia, hyperreflexia
* Peripheral neuropathies
* Dementia, psychosis, personality changes
53
Megaloblastic anemias will present with _ reticulocyte counts
Megaloblastic anemias will present with **low** reticulocyte counts
* Hypoproliferative anemia
* Ineffective hematopoiesis in general (may see leukopenia and thrombocytopenia)
54
Anemia of chronic disease is most often _ cytic but can also be _ cytic
Anemia of chronic disease is most often **normocytic** but can also be **microcytic**
55
In anemia of chronic disease, _ triggers hepcidin to (increase/decrease) which causes ferroportin to _
In anemia of chronic disease, **IL-6** triggers hepcidin to **increase** which causes ferroportin to **decrease**
* Blocks iron release from enterocytes, macrophages, and hepatocytes
* Decreased iron availability
* Also RBCs have shorter lifespan
56
Anemia of chronic disease:
Iron _
Ferritin _
TIBC _
Transferrin saturation percentage _
Anemia of chronic disease:
Iron **low**
Ferritin **normal/high**
TIBC **low**
Transferrin saturation percentage **low**
57
_ is an inability to form the protoporphyrin ring
**Sideroblastic anemia** is an inability to form the protoporphyrin ring (problem with heme synthesis pathway)
58
Heme synthesis occurs in the _ of the immature erythroid cells in the _
Heme synthesis occurs in the **mitochondria** of the immature erythroid cells in the **bone marrow**
59
Once the protoporphyrin ring is synthesized, _ transfers iron to the mitochondria of the erythroid precursor to incorporate into the ring
Once the protoporphyrin ring is synthesized, **macrophages** transfers iron to the mitochondria of the erythroid precursor to incorporate into the ring
60
In sideroblastic anemia, what happens when iron is sent to the mitochondria?
Iron cannot be incorporated into the ring --> *build up of iron in the mitochondria* --> **leads to ring sideroblast in the bone marrow**
61
**Pappenheimer bodies**: iron deposits in the peripheral blood on a prussian blue stain
* Indicative of sideroblastic anemia
62
Explain the relationship with free radicals in sideroblastic anemia
When iron stores in the bone marrow are increased this increases the production of free radicals --> increased RBC hemolysis --> further increasing iron --> iron overload
63
The congenital cause of sideroblastic anemia is a _
The congenital cause of sideroblastic anemia is an **x-linked deficiency in ALA synthase**
64
4 acquired causes of sideroblastic anemia
1. Vitamin B6 deficiency (Isoniazid)
2. Lead poisoning
3. Copper deficiency
4. Zinc overdose
65
_ is a unique phenomenon which may be observed on peripheral blood smear for sideroblastic anemia
**Dimorphism** is a unique phenomenon which may be observed on peripheral blood smear for sideroblastic anemia
* Def: two populations of RBCs on smear; one microcytic, one normocytic
66
Sideroblastic anemia:
Iron _
Ferritin _
Transferrin saturation _
TIBC _
Sideroblastic anemia:
Iron **high**
Ferritin **high**
Transferrin saturation **high**
TIBC **low**
67
_ is a type of iron chelation therapy that may be used to treat sideroblastic anemia
**Deferoxamine** is a type of iron chelation therapy that may be used to treat sideroblastic anemia
68
Pancytopenia in a peripheral blood smear is indicative of _ anemia
**Pancytopenia** in a peripheral blood smear is indicative of **aplastic anemia**
* Leukopenia
* Thrombocytopenia
* Anemia
69
Aplastic anemia occurs from damage to _ stem cell progenitors
Aplastic anemia occurs from damage to **myeloid hematopoietic** stem cell progenitors
70
Aplastic anemia
71
5 causes of aplastic anemia
"Reducing volume from inside diaphysis"
* **Radiation**
* **Viruses** (EBV, hepatitis)
* **Fanconi anemia**
* **Idipathic reasons**
* **Drugs** (chloramphenicol, carbamazepine, azathioprine)
72
_ is a hereditary mutation associated with short stature, cafe au lait spots, thumb/radial defects, and predisposition to aplastic anemia
**Fanconi anemia** is a hereditary mutation associated with short stature, cafe au lait spots, thumb/radial defects, and predisposition to aplastic anemia
73
Fanconi anemia is an autosomal recessive _ defect
Fanconi anemia is an autosomal recessive **DNA repair** defect (cannot repair DNA cross-links)
* Diagnosed with chromosome breakage analysis
74
To treat aplastic anemia we can give a bone marrow stimulating medication _
To treat aplastic anemia we can give a bone marrow stimulating medication **eltrombopag (EPAG)**
* Thrombopoietin receptor agonist --> increases production of myeloid cell lines
75
Explain the pathogenesis of anemia of chronic liver disease
Liver cirrhosis impedes blood flow --> splenomegaly --> RBC sequestration in the spleen --> anemia
76
Explain the pathogenesis of anemia of chronic renal disease
Cells that make EPO get damaged --> decreased EPO --> decreased bone marrow production of RBCs --> anemia
77
What are some examples of non-hemolytic normocytic anemias?
* Anemia of chronic disease
* Aplastic anemia
78
Name the hemolytic, normocytic anemias
* **Membrane defects**: hereditary spherocytosis, paroxysmal nocturnal hemoglobinuria
* **Enzyme deficiencies**: G6PD, pyruvate kinase deficiencies
* **Hemoglobinopathies**: sickle cell anemia, HbC disease
* **Extrinsic:** autoimmune, microangiopathic, infections
79
Name the common clinical features of hemolytic anemia
* Normocytic
* Elevated reticulocyte
* High LDH
* High unconjugated bilirubin
* Increased red blood cells in the marrow
* Decreased serum haptoglobin
80
Hemoglobinopathy
**Hemoglobinopathy** is an inherited disease with a mutation in one of the globin chain genes, alpha or beta
* The most common hemoglobinopathy is sickle cell disease
81
Sickle cell disease is a point mutation in the _ globin and exchanges _ for _ at position _
Sickle cell disease is a point mutation in the **beta** globin and exchanges **valine** for **glutamic acid** at position **6**(Glu --> Val)
* Valine is hydrophobic --> formation of rods
82
What does it mean to have the "sickle cell trait"
**Sickle cell trait** is one abnormal beta globin gene
* Recall that sickle cell is autosomal recessive and requries two abnormal beta globin genes
* Experience milder symptoms
* Hematuria, renal papillary necrosis, at risk for medullary renal carcinoma
83
Conditions that shift the oxygen dissociation curve to the _ promote sickling; explain
Conditions that shift the oxygen dissociation curve to the **right** promote sickling
* Conditions include increased lactic acid, CO2, 2-3BPG, altitude, temperature
* These promote the taut state of Hb which exposes the abnormal hydrophobic valine residues --> causes Hb to polymerize to hide valine
84
What causes sickle cell to be so painful?
Sickle cells are not flexible like normal cells and they can polymerize into rods -->
Get trapped in capillaries throughout body and spleen --> *vaso-occlusive crises* --> pain and ischemia
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The lifespan of a sickle RBC is _
The lifespan of a sickle RBC is **10-30 days**
* They lyse easier and get removed by splenic macrophages
86
Identify the Hb alleles on the hemoglobin electrophoresis
87
What unique features will be present on PBS for sickle cell?
**Target cells** (nonspecific) and **Howell-Jolly bodies** (DNA remnants that are usually removed by the spleen)
88
Sickle Cell Anemia:
MCV:
Reticulocyte count:
Sickle Cell Anemia:
MCV: **normocytic**
Reticulocyte count: **increased**
89
Name some of the complications associated with sickle cell anemia
* Vaso-occlusive crises
* Avascular necrosis of the hip
* Acute chest syndrome
* Stroke
* Priapism
* Osteomyelitis (salmonella)
* Functional asplenia
90
Patients with sickle cell may be treated with a medication called _ to increase the amount of fetal hemoglobin
Patients with sickle cell may be treated with a medication called **hydroxyurea** to increase the amount of fetal hemoglobin
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_ are disorders in which the body can't make enough alpha or beta globin chains
**Thalassemias** are disorders in which the body can't make enough alpha or beta globin chains
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We have a total of _ alpha globin genes and they are found on chromosome _
We have a total of **4 alpha globin genes** and they are found on **chromosome 16**
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We have a total of _ beta globin genes on chromosome _
We have a total of **2 beta globin genes** on **chromosome 11**
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Thalaseemia:
MCV:
MCHC:
RDW:
RBC count:
Thalaseemia:
MCV: **microcytic**
MCHC: **low**
RDW: **normal, high (severe)**
RBC count: **low**
95
What is the inheritence pattern of Glucose-6-Phosphate Dehydrogenase deficiency?
X-linked recessive
96
Patients with G6PD deficiency cannot produce NADPH to regenerate reduced glutathione --> leads to _ and _
Patients with G6PD deficiency cannot produce NADPH to regenerate reduced glutathione --> leads to **oxidative stress** and **lysis**
97
Signs of hemolytic crisis in G6PD deficiency
* Hemoglobinuria
* Jaundice
* Acute kidney injury
* Flank pain
98
G6PD deficiency is mainly (intravascular/ extravascular) hemolysis and we often see _ haptoglobin
G6PD deficiency is mainly **intravascular** hemolysis and we often see **low** haptoglobin
99
Trigges of hemolytic crisis in G6PD deficiency
* Fava beans
* Medications (sulfa drugs, anti-malarials, hydrogen peroxide, asprin, chloramphenicol)
* Infection (Parvo B19)
100
What two findings may be seen on G6PD deficiency PBS?
**Heinz bodies** (denatured hemoglobin chains) and **Bite cells** (spleen takes a bite out of these cells)
101
Hereditary spherocytosis is a genetic defect that leads to abnormal formation of _
Hereditary spherocytosis is a genetic defect that leads to abnormal formation of
* **Cytoskeletal proteins**: ankyrin, spectrin
* **Anchoring protein** (holds cytoskeleton to RBC membrane): band 3, band 4.1, band 4.2
102
Triad of symptoms for hereditary spherocytosis
1. Jaundice
2. Anemia
3. Splenomegaly
103
Hereditary spherocytosis:
MCV:
RDW:
MCHC:
Other:
Hereditary spherocytosis:
MCV: **normocytic**
RDW: **high**
MCHC: **high**
Other: **elevated bilirubin, LDH, positive osmotic fragility test**
104
How do we diagnose hereditary spherocytosis using eosin-5-maleimide binding test
**eosin-5-maleimide binding test** binds cytoskeleton proteins
* We would see **decreased fluorescence** on flow cytometry because they don't have as many normal cytoskeletal proteins
105
_ is a condition in which the body attacks itself with anti-RBC antibodies, marking them for destruction, leading to decreased RBC mass
**Autoimmune hemolytic anemia** is a condition in which the body attacks itself with anti-RBC antibodies, marking them for destruction, leading to decreased RBC mass
106
In warm AIHA, antibodies activate in _ regions of the body
In warm AIHA, antibodies activate in **central regions** of the body
107
In AIHA, the body makes _ antibodies that recognize self-RBC antigens --> splenic macrophages recognize the _ portion of the antibodies and bite the RBCs repeatedly --> _ cells
In **warm AIHA**, the body makes **IgG** antibodies that recognize self-RBC antigens --> splenic macrophages recognize the **Fc** portion of the antibodies and bite the RBCs repeatedly --> **spherocytes**
108
Warm AIHA is an example of (intravascular/ extravascular) hemolysis
Warm AIHA is an example of **extravascular** hemolysis --> the antibody coated RBC gets removed by the spleen
109
When might we see spherocytes?
* Hereditary spherocytosis
* AIHA
* G6PD deficiency
110
Warm autoimmune hemolytic anemia is usually caused by antibody formation secondary to _
* Acute infection
* Lymphoproliferative disorders
* Lupus
* Solid tumors
* Chronic inflammatory disease
* Medication
* Idiopathic
111
Cold AIHA antibodies activate in _ regions of the body
Cold AIHA antibodies activate in **peripheral regions** of the body, like the finger tips
* Patients experience cyanosis and pain in the extremities
112
In cold AIHA, the body makes _ antibodies
In cold AIHA, the body makes **IgM** antibodies
* Causes **agglutination** of RBCs
113
Cold AIHA is an example of (intravascular/ extravascular) hemolysis
Cold AIHA is an example of **both intravascular and extravascular** hemolysis
* Intravascular --> IgM activates complement to destroy RBCs
* Extravascular --> the spleenic macrophages remove RBCs
114
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Cold autoimmune hemolytic anemia is usually caused by antibody formation secondary to _
* Idiopathic
* Mycoplasma infection
* Mono infection
* Lymphoproliferative disorders
115
AIHA lab values:
MCV:
Reticulocyte count:
Haptoglobin:
Bilirubin:
Other:
AIHA lab values:
MCV: **normocytic**
Reticulocyte count: **high**
Haptoglobin: **low** (cold AHA)
Bilirubin: **high**
Other: **positive direct coombs test (DAT)**
116
_ is a condition in which RBCs are torn apart within tiny vessels creating RBC fragments (schistocytes) on PBS
**Microangiopathic hemolytic anemia** is a condition in which RBCs are torn apart within tiny vessels creating RBC fragments (schistocytes) on PBS
* Usually caused by draping of fibrin strands across the vessel lumen
117
Causes of microangiopathic hemolytic anemia:
* DIC
* TTP
* HUS
* HELLP
* Hypertensive emergency
* Prosthetic heart valve
