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Blood and Cancer > Day 1 LOL - Hematopoiesis and Anemias > Flashcards

Day 1 LOL - Hematopoiesis and Anemias Flashcards

1
Q

What makes up the formed elements in the blood?

A

RBCs, WBCs, platelets

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2
Q

Which chemokine attracts hematopoietic stem cells to the bone marrow?

A

CXCL12

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3
Q

What effect does adipose tissue in the bone marrow have on hematopoiesis?

A

Fat in the bone marrow downregulates hematopoiesis

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4
Q

What are the three key properties of a stem cell?

A

Ability to/for…

  1. Proliferate
  2. Differentiate
  3. Self-renew
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5
Q

What are the two ways by which hematopoietic stem cells can divide? In what condition are each favored?

A

Symmetric division: both daughter cells either remain HSCs or differentiate. Favored when there is hematopoietic stress.

Asymmetric division: one daughter cell remains a HSC and the other one differentiates. Happens under normal conditions.

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6
Q

What types of effector cells are derived from myelopoiesis?

A
  1. Platelets
  2. RBCs
  3. Mast cells
  4. Granulocytes (neutrophils, eosinophils, basophils - the Phils)
  5. Macrophages
  6. Myeloid dendritic cells

Or, everything except lymphocytes (including plasma cells), NK cells, and lymphoid dendritic cells.

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7
Q

Regulation of myelopoiesis by ________ ________ occurs at the level of….?

A

Regulation of myelopoiesis by growth factors occurs at the level of myeloid progenitor cells.

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8
Q

3 important GFs that regulate myelopoiesis are erythropoietin (EPO), thrombopoietin (TPO), and granulocyte colony-stimulating factor (G-CSF). Name the cell type that each GF acts on.

A

EPO acts on early erythroid progenitors.

TPO acts on myeloid progenitors to skew differentiation towards megakaryocytes.

G-CSF is a GF for neutrophil progenitors.

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9
Q

For what conditions are recombinant EPO used to treat?

A

Anemias from renal failure, chronic inflammation, and myelodysplastic syndromes.

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10
Q

For what conditions are G-CSF used to treat?

A

Drug-induced neutropenia (usually after chemo) to reduce the period of neutropenia.

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11
Q

Can you treat patients with thrombocytopenia with TPO?

A

Yeah

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12
Q

Regulation of lymphopoiesis occurs at what levels?

A

At both the level of lymphocyte progenitors and mature lymphocytes

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13
Q

What cytokine stimulates early lymphoid progenitor expansion?

A

IL-7

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14
Q

Which cytokine promotes NK cell differentiation?

A

IL-15

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15
Q

Describe how transcription factors dictate lymphoid progenitor differentiation.

A

NOTCH signals (TFs made in the microenvironment of the marrow) induce T cell differentiation, while an absence of NOTCH –> B cell differentiation

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16
Q

Do myeloid progenitors adopt particular traits that allow certain hematopoietic factors to control growth and survival? How does this ish apply to cancer?

A

Tru dat.

Tumors are often comprised of cancer cells that contain mutated transcription factors (promotors or repressors)

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17
Q

In which organs does embryologic hematopoiesis occur?

A

Early: yolk sac
Liver from 6 weeks gestation until birth
Bone marrow from 5 months gestation onwards

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18
Q

True or false: myeloid progenitor cells generally get bigger as they mature, and the nuclear:cytoplasmic ratio increases.

A

False.

They get smaller, nuclear:cytoplasmic ratio decreases

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19
Q

Define anemia.

A

Not enough RBCs for some reason

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20
Q

Which two lab values tell you if a patient is anemic? What is one potential confounder for using these values?

A
  1. Hematocrit
  2. Hb content

If there is concomitant volume loss, then HCT and Hb will be normal, despite low total RBC volume

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21
Q

Why do anemic patients appear pale?

A

Shunting of blood away from skin –> vital organs

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22
Q

Generally, what is the cardiac output of an anemic person compared to a normal person?

A

CO is increased, especially during exercise

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23
Q

How does anemia shift the oxygen binding curve of hemoglobin? Why? How does this help anemic patients compensate for the condition?

A

It shifts the curve to the right (lower affinity) because there are increased levels of 2,3-DPG. This allows for more O2 unloading at the tissues - a compensatory mechanism.

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24
Q

Anemias can be divided into 3 broad categories. What are they?

A
  1. Decreased RBC production
  2. Increased RBC destruction
  3. Blood loss (most common)
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25
WTF is a reticulocyte?
The immediate precursor of a mature erythrocyte.
26
How can reticulocyte count help you distinguish among the types of anemia in a patient?
If the reticulocyte count is low, it means there is messed up production, because with blood loss or destruction, EPO is high and the marrow is trying to make a bunch of new RBCs.
27
What morphological type of anemia does iron deficiency cause? What other diseases cause this morphological type of anemia?
Microcytic, hypochromic Others are thalassemias, sideroblastic anemia.
28
What is the bone marrow transplant conditioning regimen for neoplastic and non-neoplastic diseases, respectively?
neoplastic - chemotherapy +/- radiation non-neoplastic - chemotherapy
29
What values are included in "red blood cell indices?"
MCV and mean hemoglobin concentration (MCHC)
30
What morphologic type of anemia is seen in inflammatory syndromes?
Normocytic
31
What are 2 common symptoms of GVHD? What are two common lab/histology findings?
- Rash - Diarrhea - Elevated liver function enzymes (AST and ALT) - Lymphocytes in tissue with epithelium undergoing apoptosis
32
Do proximal tubular cells reabsorb alpha-beta hemoglobin dimers?
Yeah
33
Define aplastic anemia.
A lack of hematopoietic precursor cells in the marrow --> pancytopenia.
34
What is the most common cause of aplastic anemia?
Iatrogenic: chemotherapy, radiation
35
How does one diagnose aplastic anemia?
Marrow biopsy showing 10% cellularity (35-50% is normal)
36
What is the treatment for aplastic anemia?
Discontinue drugs/exposures. Stem cell transplant if HLA match can be found. If no match, try immunosuppression w/ cyclosporine, antithymocyte globulin.
37
How do tumors cause anemia? (2 ways)
1) necrosis of tumor core causes the release of inflammatory cytokines 2) metastasis to bone messes with hematopoietic stem cell niche
38
Name two diseases characterized by congenital aplastic anemia.
1. Fanconi anemia | 2. Diamond-Blackfan anemia
39
What is the inheritance pattern of Fanconi anemia? Name some other clinical manifestations of the disease.
Autosomal recessive. Cafe-au-lait spots. Short stature. Skeletal defects (lacking a thumb often), gonadal, renal defects.
40
What are the 3 types of hematopoietic stem cell transplantations?
Autologous (HSCs come from patient) Allogenic (HSCs come from a genetically distinct donor) Syngeneic (HSCs come from patient's identical twin)
41
What genes are important in hematopoietic stem cell transplantations?
HLA genes (MHC genes)
42
How can renal insufficiency cause anemia?
loss of functional nephrons decreases the amount of Epo secretion.
43
Is anemia of renal insufficiency severe? Do patients often require transfusions?
yes! yes!
44
Your patient has metastatic lymphoma and has pancytopenia. Peripheral blood smear shows tear-drop red cells and nucleated red cells. What is your diagnosis?
Myelophthisic anemia
45
WTF is transferrin?
Blood transport protein for iron
46
WTF is ferritin?
Protein that allows for safe intracellular storage of iron
47
WTF is hepcidin?
Circulating hormone that binds to ferroportin (the plasma membrane transporter that lets GI epithelial cells and macrophages release iron into the blood) and results in its endocytosis and degradation - end result is less absorption of iron and less circulating iron
48
Can hemolytic anemia cause iron overload?
Yeah
49
Name 3 endocrine hypofunctions that can cause anemia
- Hypothyroidism - Addison disease - Hypogonadism and hypopituitarism
50
Ferritin denatures to form _______, from which iron is not easily mobilized.
hemosiderin
51
Iron loss in a non-menstruating person occurs daily by what mechanism?
Epithelial cell shedding.
52
What does a low transferrin saturation level tell you?
The person is probably iron deficient
53
Can you use serum ferritin levels as a surrogate for measuring a person's iron stores?
Yeah
54
What is the most common cause of iron deficiency?
Blood loss
55
Name 5 clinical features that are specific to iron-deficiency anemia.
1. Evince pica (need to chew on non-nutritive substances) 2. Koilonychia (concave nail beds) 3. Fissures at corners of the mouth 4. Plummer-Vinson syndrome (dysphagia) 5. Impaired cognition in kids
56
Would you expect MCV to be increased or decreased in a patient with iron-deficiency anemia?
Decreased (it causes microcytic anemia!)
57
Your young female patient presents with shortness of breath, they appear pale and you do a blood smear that shows microcytic red cells, pencil forms, and anisocytosis. What is at the top of your DDx?
Iron-deficiency anemia
58
What is the most common mutation that causes hereditary hemochromatosis?
Single missense mutation (C282Y) in the HFE gene
59
What is the molecular defect causing hereditary hemochromatosis?
Mutated/messed up hepcidin --> unregulated iron uptake and release from GI cells and splenic macrophages.
60
What is the Tx for hereditary hemochromatosis?
Bleed them out (phlebotomy)
61
Can patients that require frequent blood transfusions get a secondary hemosiderosis?
Yeah!
62
What substances could you check for that would help you differentiate B12 deficiency from folate deficiency?
Increased serum methylmalonate (cuz B12 is needed for methylmalonyl-CoA --> succinyl-CoA) and homocysteine = B12 deficiency Increased serum homocysteine but normal methylmalonate = folate deficiency
63
What causes sideroblastic anemia?
Most common: toxin exposure (alcohol or chloramphenicol) Congenital: X-linked ALAS2 gene that encodes delta-ALA synthase
64
Meow tell me why cobalamin (B12) and folate deficiency cause red cells to be bigger (macrocytic).
The vitamin deficiency screws up DNA synthesis, but in cells that don't apoptose, transcription and translation machinery still work, so cells get big.
65
Briefly describe how B12 is absorbed in the GI tract.
B12 binds to intrinsic factor, IF-B12 binds to cubilin receptors in the distal ileum --> endocytosis --> portal circulation to liver --> transfer to transcobalamin (transport protein for B12) Somehow, most of the circulating cobalamin in the serum is bound to haptocorrin
66
What changes are seen in the bone marrow in a patient with megaloblastic anemia?
Increased cellularity, stunted nuclear maturation (nuclear-cytoplasmic dyssynchrony), enlarged myeloid precursors
67
How do you treat B12 and folate deficiency?
For B12 deficiency, give B12 parenterally (to avoid absorption problems). For folate deficiency, give oral folic acid (1mg/day) and also do a full nutritional eval
68
What is the pathophysiology behind graft versus host disease?
damage to epithelium via conditioning or endotoxins results in the activation of the transplanted immune system. Activated T cells recognize host tissue and mounts an attack
69
What are 2 common symptoms of GVHD? What are two common lab/histology findings?
- Rash - Diarrhea - Elevated liver function enzymes (AST and ALT) - Lymphocytes in tissue with epithelium undergoing apoptosis
70
What substances could you check for that would help you differentiate B12 deficiency from folate deficiency?
Increased serum methylmalonate and homocysteine = B12 deficiency Increased serum homocysteine but normal methylmalonate = folate deficiency
71
What is graft versus tumor effect?
HSCT aimed to activate donor immune system against host tumor(s)
72
What is nonmyeloablative HSCT?
HSCT that involves incomplete conditioning. Meaning, conditioning doesn't completely wipe out patient's marrow, which equates to a partial marrow transplant
73
Does chronic inflammation typically lead to anemia?
yes
74
How does HIV lead to anemia?
it infects progenitor cells
75
How does babesiosis lead to anemia?
parasite infects and destroys circulating RBCs
76
How do tumors cause anemia? (2 ways)
1) necrosis of tumor core causes the release of inflammatory cytokines 2) metastasis to bone messes with hematopoietic stem cell niche
77
What would you see on a peripheral blood smear from a patient with megaloblastic anemia?
1. Macro-ovalocytes 2. Anisocytosis (variation in RBC size) 3. Hypersegmented neutrophils
78
Pallor, scleral icterus, GLOSSITIS in an anemic patient. What is your Dx?
Megaloblastic anemia
79
What type of anemia is caused by a lack of intrinsic factor and/or atrophy of epithelial cells in the distal ileum?
Pernicious anemia
80
Should you give folate to a B12 deficient person that has neurologic symptoms?
No, it'll make the neuro symptoms worse for some reason
81
How do you treat B12 and folate deficiency?
For B12 deficiency, give B12 parenterally (to avoid absorption problems). For folate deficiency, give oral folic acid (1mg/day)
82
How do autoimmune disorders cause anemia? example of a disorder that causes anemia
they cause systemic inflammation SLE
83
Is anemia of chronic inflammation associate with a systemic derangement of iron homeostasis?
it sure is
84
What are the 5 lab findings in anemia of chronic inflammation? What is the pathophysiology behind these levels?
- increased macrophage iron storage - increased serum ferratin - decreased serum iron - decreased total transferrin - low reticulocytes inflammation results in increased levels of hepcidin (inhibits iron release from macrophages and iron absorption via enterocytes)
85
What is the treatment for anemia of chronic inflammation
- treat underlying cause of inflammation | - some may benefit from Epo
86
How can renal insufficiency cause anemia?
loss of functional nephrons decreases the amount of Epo secretion.
87
Is anemia of renal insufficiency severe? What treatment does it often require?
yes! transfusions
88
What are lab findings in anemia of renal insufficiency?
- Low reticulocyte index | - Burr-shaped RBS with evenly scalloped boarders
89
What is the mainstay treatment of anemia of renal insufficiency? What complications do you need to watch for?
- recombinant human Epo (rhEpo) - Watch the Hb levels. If they approach or exceed 12g/dL, patients become susceptible to thrombosis and cardiovascular mortality
90
What 2 lab findings are common in anemia due to liver disease?
- Target cells | - Low reticulocyte index
91
How are target cells formed?
Target cells are formed due to the abnormal uptake of lipids and cholesterol into the RBC membrane, increasing the surface to volume ratio
92
What is a common cause of anemia of liver disease?
Alcohol!
93
Why is alcohol caused anemia of liver disease so severe? (name 4 reasons)
- Alcohol suppresses hematopoiesis leading to anemia and pancytopenia - Alcohol damages the liver - Alcoholics are malnourished which leads to decreased folate intake - Alcohol messes with GI lining causing ulcers and bleeding, leading to iron loss

Blood and Cancer (10 decks)

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