Hematology Flashcards

1
Q

Erythropoietin is formed by which organs?

A

90% made by the kidney

10 % Liver

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2
Q

What stimulates renal production of EPO?

A

Hypoxia

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3
Q

How does EPO exert its effects?

A

Triggers hematopoietic stem cells to produce more proerythroblasts

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4
Q

What is the result of vitamin B12 or folic acid deficiency?

A

Maturation failure during the process of erythropoiesis.

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5
Q

Final maturation of RBCs requires what?

(2 factors)

A

Vitamin B12

Folic Acid

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6
Q

What is pernicious anemia?

A

Atrophic gastric mucosa (GI defect) leads to decreased B12 absorption.

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7
Q

What is intrinsic factor?

A

Glycoprotein that binds to Vit B12 and protects B12 from digestion. Then the intrinsic factor-B12 complex is absorbed by pinocitosis in the ileum.

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8
Q

What cells produce intrinsic factor?

A

The parietal cells of the gastric glands

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9
Q

At what RBC cell stage does the process of hemoglobin synthesis start?

A

A the proerythroblast stage

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10
Q

What are the components of hemoglobin?

A

Heme - molecule

Globin - long polypeptide

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11
Q

What is the total iron distribution in the body?

A

Hemoglobin - 65%

Ferretin - 15-30%

Myoglobin - 4%

Compounds of intracellular oxidation - 1 %

Transferrin - 0.1%

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12
Q

How is iron absorbed in the GI?

A

Iron combines with apotransferrin in the small intestine.

Apotransferrin is converted to transferrin.

Transferrin transports Iron in plasma.

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13
Q

How is iron (transferrin form) is distributed and stored in the cell?

A

Transferrin circulates iron and deposits it in:

Liver and reticuloendothelial cells of bone marrow

Once inside the cell - iron combines with apoferritin to form ferritin.

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14
Q

What happens when iron plasma levels decrease?

A

Iron dissociates from ferritin in the cells and then it is recirculated to where it is needed (via transferrin)

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15
Q

How is Iron stored in the cell?

A

Via ferritin

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16
Q

How is iron transported in the blood?

A

Transferrin

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17
Q

Where does transferrin bind particularly strongly?

A

Receptors of erythroblasts and bone marrow (cells that need large amounts of iron)

Transferrin is endocytosed and it delivers iron directly to the mitochondria.

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18
Q

What receptor does transferrin use to bring iron into the cell? How is it brought into the cell?

A
  1. Transferrin receptor 1 (TFR1) - outside of the cell
  2. Once transferrin is bound to TFR1 - endosome is formed.
  3. DMT1 receptor is within endosome - Is proton pump that brings iron into cytoplasm
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19
Q

What are the two main receptors involved in cellular uptake of Iron?

A

Transferrin receptor 1 (TFR1) - Outside cell > stimulates endosome

Divalent metal transporter 1 (DMT1) - Within endosome > brings it into cytoplasm

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20
Q

What is the primary regulator of iron homeostasis?

A

Hepcidin

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21
Q

What organ produces hepcidin?

A

Liver mainly

Some is produced by monocytes/macrophages

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22
Q

In what part of the small intestine is iron mostly absorbed?

A

Duodenum

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23
Q

What is the major effect of hepcidin?

A

Inhibits iron export from cells

Causes iron retention in the cells

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24
Q

What triggers hepcidin expression?

A

Iron overload

Inflammation

Hypoxia

Anemia

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25
Q

What is aplastic anemia?

A

Anemia from nonfunctioning bone marrow (e.g. cancer, radiation, toxicity)

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26
Q

What is megaloblastic anemia?

A

Results from lack of B12 (e.g. pernicious anemia), folic acid or intrinsic factor.

=Slow RBC production = erythrocytes grow into large megaloblasts

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27
Q

What are the types of polycythemia

A
  1. Physiologic polycythemia - High altitude, R-L shunt, chronic hypoxia
  2. Polycythemia vera - Genetic defect in RBC line
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28
Q

What is the effect of hepcidin in the GI?

A

Decreased iron absorption by the duodenum

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29
Q

What are the signs of acute iron toxicity?

A

Early - GI signs

Followed by circulatory collapse

Last stage - Pulmonary edema, hepatic failure, cyanosis, coma, death

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30
Q

In which condition would you expect development of microcytosis before hypochromia?

A

Iron deficiency anemia - RBC progressively get smaller (MVC), then decrease in color (MCHC)

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31
Q

How many subunits does hemoglobin have?

A

Four - each contain a heme moiety (contains iron)

32
Q

Oxygen binds to iron in what state?

A

Ferrous state (Fe2+)

33
Q

What is methemoglobin?

A

Iron in the Fe3+ state

Does not bind oxygen

34
Q

What are the feline blood types? Which one is more common?

A

A, B and AB

A (≥94% of non-pedigree cats)

35
Q

Which one is worse in transfusion medicine?

Type A cat getting type B blood

Type B cat getting type A blood

A

Type B cat getting type A blood

36
Q

Regarding feline RBC antigen and genetics:

Which allele is dominant? Type A or type B

A

Type A is dominant over type B

37
Q

What is the most antigenic blood type in dogs?

A

DEA 1.1

38
Q

Why are type B cats so reactive to type A blood?

A

Type B cats have naturally occurring antibodies against the type A antigen (anti-A antibodies). These antibodies are strong hemagglutinins and hemolysins (IgM).

(Type A cats have weak anti-B antibodies)

39
Q

What transports iron across the basement membrane?

A

Ferroportin

40
Q

What are acanthocytes?

A

RBC with excess membrane = finger-like projections.

Associated with lipid loading. They have increased cholesterol:phospholipid ratio

41
Q

What are acanthocytes associated with?

A

Liver disease

Renal disease

Splenic disease (e.g. HSA, LSA)

42
Q

What are target cells?

A

Increased membrane/cytoplasm ratio.

Associated with reticulocytes in circulation. Immature cells.

NORMAL cholesterol:phospholipid ratio

43
Q

What is the progression of erythroblast maturation?

A

Rubriblast; prorubricyte; rubricyte; metarubricyte (nucleated RBC); Reticulocyte; erythrocyte

“Rarely, politicians rub me repeatedly”

44
Q

What are the 3 broad processes involved in anemia of chronic disease?

A
  1. Altered iron metabolism
  2. Decreased red blood cell survival
  3. Decreased bone marrow erythropoesis
45
Q

Erythrocytes do not have mitochondria. How do they derive their energy?

A

Anaerobic glycolysis

46
Q

What is phosphofructokinase (PFK) deficiency?

A

Autosomal Recessive condition in springer spaniels and american cocker spaniels.

Leads to exertional myopathy and episodic hemolysis

47
Q

What cells in the kidney produce EPO?

A

Renal tubular epithelial cells

48
Q

What are the contents of eosinophil granules?

A
  1. Major basic protein - mast cell /basophil degranulation
  2. Eosinophilic cationic protein - creates pores
  3. Eosinophilic peroxidase
  4. Eosinophil derived neurotoxin
49
Q

What receptor does clopidogrel (thienopyridines) work in?

A

Block ADP receptors (P2Y12) → prevents a platelet plug from forming because platelets cant be activated

50
Q

What factors make up the extrinsic pathway of coagulation?

A

VII

Tissue factor

51
Q

What factors make up the common pathway of coagulation?

A

I, II, V and X

(Remember - 1 x 2 x 5 = 10)

52
Q

What factors make up the intrinsic pathway of coagulation?

A

VIII, IX, XI, XII

53
Q

What is the only protein that is attached to the membrane surface?

A

Tissue factor

54
Q

What factor is deficient in Hemophilia A

A

Factor VIII

55
Q

What factor is deficient in Hemophilia B

A

Factor IX

56
Q

What is the only coagulation factor that routinely circulates in its active form?

A

Factor VII (1% is activated at any given time)

57
Q

What forms the prothrombinase complex?

A

Factors Xa and VIIa

58
Q

What does the prothrombinase complex do?

A

Cleaves prothrombin to thrombin (Factor IIa)

59
Q

What does factor XIII do?

A

Modifies the polymerized fibrin to form cross links between fibrin strands

60
Q

What do D-dimers test for?

A

Degradation of insoluble cross-linked fibrin

61
Q

What does an elevated PT and normal PTT indicate?

A

Factor VII deficiency

62
Q

What factor deficiency in cats is usually clinically insignificant?

A

Factor XII

63
Q

What are acquired anticoagulants?

A

Antibodies against specific factors to bind and inactivate.

64
Q

How does hypophosphatemia cause hemolytic anemia?

A

Decreased ATP stores

65
Q

How does systemic inflammation lead to anemia?

A

IL-6 leads to hepcidin production, which results in relative iron deficiency.

66
Q

What breed is predisposed to leukocyte adhesion deficiency?

A

Irish Setters - They get severe infections as puppies

67
Q

Severe combined X-linked immunodeficiency results in the deficit of what cytokine?

A

IL-2

68
Q

Mechanism of action of Aspirin

A

Inhibits COX 1 (also COX 2 but less so) and prostaglandin synthase.

Results in decreased prostaglandin and thromboxane A2

Irreversible inhibition of platelet aggregation as they cannot produce new COX

69
Q

Mechanism of action of aminocaproic acid

A

Inhibits fibrinolysis - Inhibits plasminogen activator substances

70
Q

MOA of warfarin

A

Inhibits vitamin K epoxide reductase - Inhibits the action of vitamin K on coag factors II, VII, IV, X

71
Q

Clopidogrel MOA

A

Blocks ADP receptors and Inhibits P2Y12 receptor on platelets

72
Q

What is copper bound to in the plasma?

A

Ceruloplasmin

73
Q

How are Heinz bodies formed?

A

Oxidation of exposed sulfhydryl groups on hemoglobin causes formation of disulfide bonds and distortion of the tertiary structure of the hemoglobin molecule = Precipitation of hemoglobin

74
Q

In what species Heinz bodies may be normal?

A

Cats

75
Q

Acanthocytes have an (increased/decreased) cholesterol:phospholipid ratio?

A

Increased

76
Q

Describe iron absorption in the gut.

A

Iron is absorbed in the apical membrane of GI epithelium by DMT-1

Moves through ferroportin in basolateral membrane of GI epithelium.

Ceruloplasmin converts it from Fe2 to Fe3

Fe3 binds to transferrin in the bloodstrem