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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
Q

WTF is a reticulocyte?

A

The immediate precursor of a mature erythrocyte.

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26
Q

How can reticulocyte count help you distinguish among the types of anemia in a patient?

A

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.

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27
Q

What morphological type of anemia does iron deficiency cause? What other diseases cause this morphological type of anemia?

A

Microcytic, hypochromic

Others are thalassemias, sideroblastic anemia.

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28
Q

What is the bone marrow transplant conditioning regimen for neoplastic and non-neoplastic diseases, respectively?

A

neoplastic
- chemotherapy +/- radiation

non-neoplastic
- chemotherapy

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29
Q

What values are included in “red blood cell indices?”

A

MCV and mean hemoglobin concentration (MCHC)

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30
Q

What morphologic type of anemia is seen in inflammatory syndromes?

A

Normocytic

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31
Q

What are 2 common symptoms of GVHD? What are two common lab/histology findings?

A
  • Rash
  • Diarrhea
  • Elevated liver function enzymes (AST and ALT)
  • Lymphocytes in tissue with epithelium undergoing apoptosis
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32
Q

Do proximal tubular cells reabsorb alpha-beta hemoglobin dimers?

A

Yeah

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33
Q

Define aplastic anemia.

A

A lack of hematopoietic precursor cells in the marrow –> pancytopenia.

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34
Q

What is the most common cause of aplastic anemia?

A

Iatrogenic: chemotherapy, radiation

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35
Q

How does one diagnose aplastic anemia?

A

Marrow biopsy showing 10% cellularity (35-50% is normal)

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36
Q

What is the treatment for aplastic anemia?

A

Discontinue drugs/exposures.

Stem cell transplant if HLA match can be found.

If no match, try immunosuppression w/ cyclosporine, antithymocyte globulin.

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37
Q

How do tumors cause anemia? (2 ways)

A

1) necrosis of tumor core causes the release of inflammatory cytokines
2) metastasis to bone messes with hematopoietic stem cell niche

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38
Q

Name two diseases characterized by congenital aplastic anemia.

A
  1. Fanconi anemia

2. Diamond-Blackfan anemia

39
Q

What is the inheritance pattern of Fanconi anemia? Name some other clinical manifestations of the disease.

A

Autosomal recessive.

Cafe-au-lait spots.
Short stature.
Skeletal defects (lacking a thumb often), gonadal, renal defects.

40
Q

What are the 3 types of hematopoietic stem cell transplantations?

A

Autologous (HSCs come from patient)

Allogenic (HSCs come from a genetically distinct donor)

Syngeneic (HSCs come from patient’s identical twin)

41
Q

What genes are important in hematopoietic stem cell transplantations?

A

HLA genes (MHC genes)

42
Q

How can renal insufficiency cause anemia?

A

loss of functional nephrons decreases the amount of Epo secretion.

43
Q

Is anemia of renal insufficiency severe? Do patients often require transfusions?

A

yes!

yes!

44
Q

Your patient has metastatic lymphoma and has pancytopenia. Peripheral blood smear shows tear-drop red cells and nucleated red cells. What is your diagnosis?

A

Myelophthisic anemia

45
Q

WTF is transferrin?

A

Blood transport protein for iron

46
Q

WTF is ferritin?

A

Protein that allows for safe intracellular storage of iron

47
Q

WTF is hepcidin?

A

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
Q

Can hemolytic anemia cause iron overload?

A

Yeah

49
Q

Name 3 endocrine hypofunctions that can cause anemia

A
  • Hypothyroidism
  • Addison disease
  • Hypogonadism and hypopituitarism
50
Q

Ferritin denatures to form _______, from which iron is not easily mobilized.

A

hemosiderin

51
Q

Iron loss in a non-menstruating person occurs daily by what mechanism?

A

Epithelial cell shedding.

52
Q

What does a low transferrin saturation level tell you?

A

The person is probably iron deficient

53
Q

Can you use serum ferritin levels as a surrogate for measuring a person’s iron stores?

A

Yeah

54
Q

What is the most common cause of iron deficiency?

A

Blood loss

55
Q

Name 5 clinical features that are specific to iron-deficiency anemia.

A
  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
Q

Would you expect MCV to be increased or decreased in a patient with iron-deficiency anemia?

A

Decreased (it causes microcytic anemia!)

57
Q

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?

A

Iron-deficiency anemia

58
Q

What is the most common mutation that causes hereditary hemochromatosis?

A

Single missense mutation (C282Y) in the HFE gene

59
Q

What is the molecular defect causing hereditary hemochromatosis?

A

Mutated/messed up hepcidin –> unregulated iron uptake and release from GI cells and splenic macrophages.

60
Q

What is the Tx for hereditary hemochromatosis?

A

Bleed them out (phlebotomy)

61
Q

Can patients that require frequent blood transfusions get a secondary hemosiderosis?

A

Yeah!

62
Q

What substances could you check for that would help you differentiate B12 deficiency from folate deficiency?

A

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
Q

What causes sideroblastic anemia?

A

Most common: toxin exposure (alcohol or chloramphenicol)

Congenital: X-linked ALAS2 gene that encodes delta-ALA synthase

64
Q

Meow tell me why cobalamin (B12) and folate deficiency cause red cells to be bigger (macrocytic).

A

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
Q

Briefly describe how B12 is absorbed in the GI tract.

A

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
Q

What changes are seen in the bone marrow in a patient with megaloblastic anemia?

A

Increased cellularity, stunted nuclear maturation (nuclear-cytoplasmic dyssynchrony), enlarged myeloid precursors

67
Q

How do you treat B12 and folate deficiency?

A

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
Q

What is the pathophysiology behind graft versus host disease?

A

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
Q

What are 2 common symptoms of GVHD? What are two common lab/histology findings?

A
  • Rash
  • Diarrhea
  • Elevated liver function enzymes (AST and ALT)
  • Lymphocytes in tissue with epithelium undergoing apoptosis
70
Q

What substances could you check for that would help you differentiate B12 deficiency from folate deficiency?

A

Increased serum methylmalonate and homocysteine = B12 deficiency

Increased serum homocysteine but normal methylmalonate = folate deficiency

71
Q

What is graft versus tumor effect?

A

HSCT aimed to activate donor immune system against host tumor(s)

72
Q

What is nonmyeloablative HSCT?

A

HSCT that involves incomplete conditioning. Meaning, conditioning doesn’t completely wipe out patient’s marrow, which equates to a partial marrow transplant

73
Q

Does chronic inflammation typically lead to anemia?

A

yes

74
Q

How does HIV lead to anemia?

A

it infects progenitor cells

75
Q

How does babesiosis lead to anemia?

A

parasite infects and destroys circulating RBCs

76
Q

How do tumors cause anemia? (2 ways)

A

1) necrosis of tumor core causes the release of inflammatory cytokines
2) metastasis to bone messes with hematopoietic stem cell niche

77
Q

What would you see on a peripheral blood smear from a patient with megaloblastic anemia?

A
  1. Macro-ovalocytes
  2. Anisocytosis (variation in RBC size)
  3. Hypersegmented neutrophils
78
Q

Pallor, scleral icterus, GLOSSITIS in an anemic patient. What is your Dx?

A

Megaloblastic anemia

79
Q

What type of anemia is caused by a lack of intrinsic factor and/or atrophy of epithelial cells in the distal ileum?

A

Pernicious anemia

80
Q

Should you give folate to a B12 deficient person that has neurologic symptoms?

A

No, it’ll make the neuro symptoms worse for some reason

81
Q

How do you treat B12 and folate deficiency?

A

For B12 deficiency, give B12 parenterally (to avoid absorption problems).

For folate deficiency, give oral folic acid (1mg/day)

82
Q

How do autoimmune disorders cause anemia? example of a disorder that causes anemia

A

they cause systemic inflammation

SLE

83
Q

Is anemia of chronic inflammation associate with a systemic derangement of iron homeostasis?

A

it sure is

84
Q

What are the 5 lab findings in anemia of chronic inflammation? What is the pathophysiology behind these levels?

A
  • 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
Q

What is the treatment for anemia of chronic inflammation

A
  • treat underlying cause of inflammation

- some may benefit from Epo

86
Q

How can renal insufficiency cause anemia?

A

loss of functional nephrons decreases the amount of Epo secretion.

87
Q

Is anemia of renal insufficiency severe? What treatment does it often require?

A

yes!

transfusions

88
Q

What are lab findings in anemia of renal insufficiency?

A
  • Low reticulocyte index

- Burr-shaped RBS with evenly scalloped boarders

89
Q

What is the mainstay treatment of anemia of renal insufficiency? What complications do you need to watch for?

A
  • recombinant human Epo (rhEpo)
  • Watch the Hb levels. If they approach or exceed 12g/dL, patients become susceptible to thrombosis and cardiovascular mortality
90
Q

What 2 lab findings are common in anemia due to liver disease?

A
  • Target cells

- Low reticulocyte index

91
Q

How are target cells formed?

A

Target cells are formed due to the abnormal uptake of lipids and cholesterol into the RBC membrane, increasing the surface to volume ratio

92
Q

What is a common cause of anemia of liver disease?

A

Alcohol!

93
Q

Why is alcohol caused anemia of liver disease so severe? (name 4 reasons)

A
  • 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

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