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POM > Hematology > Flashcards

Hematology Flashcards

1
Q

What two factors are necessary to maintain the circulation of blood in fluid state to blood vessels?

A

Fibrinolytic anticoagulant proteins

Coagulation factors, platelets

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2
Q

Describe the structure of platelets

A

Discoid
Non-nucleated
Granule-containing

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3
Q

Where and how are platelets formed?

A

Bone marrow by fragmentation of megakaryocytic cytoplasm from myeloid stem cells

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4
Q

Describe the Vasoconstriction stage of Primary Haemostasis

A

Nitric Oxide and prostacyclin concentrations are less than endothelin concentration
So vasoconstriction occurs to reduce the amount of blood being lost

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5
Q

Outline the process of Platelet Adhesion during Primary Haemostasis

A

VWF binds to collagen on the endothelium at the site of injury and then GPIb receptor on the platelet binds to VWF.
OR
platelets stick to collagen via the GPIa receptor.

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6
Q

What do the alpha granules contain?

A

VWF

Fibrinogen

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7
Q

What do dense granules contain?

A

Serotonin
ADP
Ca2+

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8
Q

How does the Activation and Degranulation of platelets occur in Primary Haemostasis?

A

Platelet and GPIb receptor change shape so that it can bind properly to the endothelium
The alpha and dense granules of platelets are released
The ADP in dense granules is what activates the GPIIIa receptors to bind to the fibrinogen

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9
Q

Describe the final step of platelet aggregation in Primary Haemostasis

A

Platelet releases Prostaglandin, Thromboxane A2, and ADP
Resulting in Positive feedback for more recruitment activation and aggregation as the platelet changes shape and many will bind to a single fibrinogen
Creating the platelet plug

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10
Q

How does Aspirin inhibit the activation of platelets?

A

Inhibits the production of thromboxane A2 by irreversibly blocking the action of cyclo-oxygenase (COX), resulting in a reduction in platelet aggregation.

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11
Q

How does the anti-platelet drug Clopidogrel work?

A

Irreversibly blocking ADP receptor (P2Y12) on the platelet cell membrane

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12
Q

What is the function of fibrin?

A

To reinforce the platelet plug at the site of injury and make it stronger

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13
Q

Describe what happens during the Initiation stage of Secondary Haemostasis

A

Extrinsic: Triggered by tissue factor (TF) on surface of endothelial cells binds to VIIa → X to Xa
Or
Intrisic: Triggered by Sub-endothelium collagen to convert XII to XIIa → XI to XIa → IX to IXa → VWF to VIIa → X to Xa
Xa leads to activation of prothrombin (Factor II) (inactive form) → Generation of small thrombin (active form)

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14
Q

What occurs in the Amplification stage of Secondary Haemostasis?

A

A small amount of thrombin mediates activation of co-factors V & VIII, zymogen (proenzyme) factor XI, and platelets

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15
Q

What is the purpose of thrombin?

A

To convert fibrinogen to fibrin

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16
Q

Outline the Propagation stage of Secondary Haemostasis

A

Factor XI converts more IX to IXa
With factor VIIIa, XIa will amplify conversion of factor X→Xa
Leading to a rapid burst in thrombin generation, which cleaves circulating fibrinogen to form insoluble clot

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17
Q

What is the function of Proteins C & S?

A

Protein C is activated when thrombin binds to thrombomodulin on endothelial cell surface
Activated protein C in the presence of protein S will inactivate factors Va and VIIIa

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18
Q

How do Antithrombin and Heparin promote anticoagulation?

A

Thrombin and factor Xa are inactivated by circulating inhibitor, antithrombin by the binding of antithrombin to endothelial cell-associated heparins.
Heparin enhances the binding capabilities of antithrombin to Factor II (prothrombin)
Inactivation of thrombin requires larger chains of heparin to wrap around both antithrombin and thrombin

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19
Q

How is Warfarin an anticoagulant?

A

It is a Vitamin K antagonist working by interfering with protein carboxylation
Therefore reduces synthesis of functional factors II, VII, IX and X by the liver
Takes several days to start working

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20
Q

What is meant by a zymogen?

A

A proenzyme = an enzyme that generates another enzyme

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21
Q

What is the function of the Fibrinolytic system?

A

To remove clot after vasculature is repaired

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22
Q

What is plasminogen?

A

The inactive zymogen form of plasmin

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23
Q

What does plasmin do?

A

Digests Fibrin into Fibrin Degradation Products - breaks down the clot
Digests Fibrinogen into Fibrinogen Degradation Products
Digests V & VII
Digests II & XII to prevent clot formation

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24
Q

Outline briefly the fibrinolytic system?

A

Tissue plasminogen activator (t-PA) converts plasminogen into plasmin to lyse the fibrin and fibrinogen to form degradation products. This activation will only happen if t-PA and plasminogen both bind to lysine residues in fibrin.

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25
Q

What is thrombosis?

A

Formation of clot within an intact blood vessel which usually obstructs blood flow

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26
Q

What 3 changes in blood could increase a person’s risk of venous thrombosis?

A

Reduced anticoagulant factors
Increased coagulant factors
Reduced fibrinolytic activity

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27
Q

Which coagulation pathway do the aPTT and PT monitor respectively?

A 
Activated partial thromboplastin time (aPTT) - intrinsic
Prothrombin Time (PT) - extrinsic
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28
Q

What is plasma?

A

The liquid component of blood that holds blood cells of whole blood in suspension

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29
Q

What type of drug can be used to stop the blood from clotting?

A

Anticoagulants

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30
Q

What separates the red cells from the plasma after the addition of an anticoagulant and centrifugation?

A

Buffy coat (platelets and leukocytes)

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31
Q

What is apheresis?

A

When the blood of a donor is collected and passed through a centrifuge to separate particular cellular components

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32
Q

How is serum generated?

A

Letting blood clot for several minutes (fewer coagulation factors and trapping cells and platelets within clot)

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33
Q

What is a buffy coat made out of?

A

Leukocytes and platelets

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34
Q

What are the differences between plasma and serum samples?

A

Plasma is faster to prepare

Serum is cleaner

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35
Q

Name the 4 main fluid compartments in humans

A

Intracellular - inside cells
Interstitial - between cells
Extracellular - outside cells
Transcellular - CSF, ocular fluid, synovial fluid

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36
Q

Where is interstitial fluid found?

A

Outside of cells - lymph drains

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37
Q

Why does interstitial fluid play an important role?

A

Carrying oxygen and nutrients to cells and also acts as a vehicle for the removal of cellular waste products

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38
Q

How is interstitial fluid drained and what is it known as when it is drained?

A

Through lymphatic vessels

Lymph

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39
Q

What do transcellular fluids include?

A

CSF, ocular fluid, synovial fluid

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40
Q

What is the most abundant plasma protein?

A

Albumin

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41
Q

Where is serum albumin produced?

A

Liver

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42
Q

What is A1AT, where is it produced and what does it do?

A

Alpha-1 antitrypsin
Produced in the liver
Inhibits proteases

43
Q

What do neutrophils release during inflammation?

A

Neutrophil elastase

44
Q

What do Beta globulins include?

A

Complement proteins C3 & C4

Transferrin

45
Q

What is the role of transferrin?

A

Transportation of iron

46
Q

Where is transferrin generated?

A

Liver

47
Q

What are the 2 main gamma globulins?

A

Immunoglobulins (antibodies)

C-Reactive Protein

48
Q

What is the most plentiful cation in plasma?

A

Na+

49
Q

What balances the charge of intracellular K+?

A 
Extracellular Cl-
Various anions (proteins, phosphorylated proteins, nucleic acids)
50
Q

Why is there typically an increase in intracellular Ca 2+?

A

Signaling events due to either the opening of calcium channels allowing influx from the exterior or the release of intracellular stores

51
Q

How are the electrolyte gradients maintained?

A

Active transport by protein pumps such as the Na+/K+ Pump

52
Q

What is the name of the protein used in the Na+/K+ pump?

A

Na+-K+-ATPase

53
Q

For every 3 Na+ actively transported out how many K+ in?

A

2

54
Q

What is the main difference between plasma and interstitial fluid?

A

Plasma contains more proteins

55
Q

What are the main functions of albumin?

A

Transportation of lipids, ions, and hormones

Maintaining osmotic pressure of the pressure

56
Q

What is hemopoiesis?

A

Formation of blood cellular components

57
Q

What is another name for red blood cells?

A

Erythrocytes

58
Q

Where are red blood cells produced and what are they derived from?

A

Bone Marrow

Hemopoietic Stem Cell → Myeloid Progenitor

59
Q

What do hemopoietic stem cells have the ability to do?

A

Self Renew: some daughter cells remain as haemopoietic stem cells
Differentiate to mature progeny

60
Q

How long does it take for bone marrow to develop hemopoietic activity?

A

10 weeks

61
Q

Where does hemopoiesis occur in adults?

A

Bone marrow of pelvis, sternum, and femur

62
Q

What is hemolysis?

A

Rupture and disruption of red blood cells

63
Q

What is erythropoiesis?

A

Production of red blood cells

64
Q

Where is erythropoietin synthesized?

A

Kidney

65
Q

What do hemopoietic growth factors regulate?

A

Hemopoiesis

66
Q

What gives rise to a pro-erythroblast?

A

Common Myeloid Progenitor

67
Q

What are the 4 things required for erythropoiesis?

A

Folic Acid
Iron
Vitamin B12
Erythropoietin

68
Q

What causes microcytic anemia?

A

Iron Deficiency and cancer

69
Q

What causes macrocytic anemia?

A

Vitamin B12 and Folate Deficiency and alcohol use

70
Q

What causes normocytic anemia?

A

Chronic conditions (e.g. diabetes, high BP)

71
Q

What is erythropoietin and how does it produce RBCs?

A

Regulates erythropoiesis
In response to hypoxia (when low O2 to the kidney), it stimulates the bone marrow to produce more RBCs in order to increase O2

72
Q

What are the 2 major functions of iron?

A

Transport O2 in Hb

Mitochondrial proteins cytochrome a, b, c

73
Q

What is the best absorbed form of iron?

A

Ferrous Iron (Fe2+)

74
Q

What are the charges of iron in the ferrous and ferric form respectively?

A

Ferrous -> 2+

Ferric -> 3+

75
Q

Why is excess iron bad?

A

There is no physiological mechanism by which Iron is excreted

76
Q

What regulates the absorption of iron in the gut?

A

Hepcidin

77
Q

What is an enterocyte?

A

Intestinal absorptive cell

78
Q

What suppresses hepcidin synthesis?

A

Erythropoietic activity

79
Q

What are folate and VB12 needed for?

A

For dTTP synthesis needed for the synthesis of thymidine (DNA base)
Folate deficiency causes problems in the production of thymidine. B12 deficiency allows cells to grow but not to divide, causing megaloblastic cells.

80
Q

What does vitamin B12 bind to in the stomach during its absorption?

A

Intrinsic factor

81
Q

Where is intrinsic factor made?

A

Gastric parietal cells

82
Q

What is pernicious anemia?

A

Inadequate secretion of IF

83
Q

What can vitamin B12 deficiency result from?

A

Lack of meat and fish

84
Q

Where does the absorption of folate take place?

A

Duodenum

85
Q

When do the requirements of folate increase?

A

Pregnancy

Low RBC production -> sickle cell anemia

86
Q

How long do red cells circulate?

A

~120 days

87
Q

Where do red cells undergo phagocytosis?

A

Spleen

88
Q

What is released from the heme (porphyrin) ring when it is recycled?

A

Iron

89
Q

What is iron bound to on its way back to the bone marrow?

A

Transferrin

90
Q

What does the catabolism of heme produce and where is this product excreted?

A

Bilirubin

Excreted in bile

91
Q

Describe the red cell membrane

A

Made up of lipid bilayer supported by protein cytoskeleton

Contains transmembrane proteins to maintain shape and flexibility

92
Q

What happens to red blood cells during hereditary spherocytosis?

A

They become spherical (spherocytes)

no central pallor

93
Q

What causes these structures?

A

Disruption of vertical linkages
Loss of part of the cell membrane without loss of cell cytoplasm
RBCs become less flexible

94
Q

What happens to those red blood cells?

A

Prematurely removed by the spleen -hemolysis

95
Q

What causes hereditary elliptocytosis?

A

Disruption of horizontal linkages

Lack of iron

96
Q

What is a heme group made of?

A

1 porphyrin ring

Fe2+

97
Q

What is the difference between adult and fetal hemoglobin?

A

Fetal - 2 alpha chains and 2 gamma chains

Adult - 2 alpha chains and 2 beta chains

98
Q

What is co-operativity?

A

When the binding of the first O2 to Hb changes the structure so that it is easier to add another O2 molecule

99
Q

Explain the Bohr Effect?

A

High CO2
Low pH
More dissociation and so easy offloading of O2 to respiring cells (right shift)

100
Q

Which shift of the sigmoid curve showing saturation of Hb at different ppO2 does Foetal Hb give?

A

Left shift

101
Q

What is 2,3-DPG and how does it work?

A

Organic phosphate product

Modulates O2 affinity of Hb by binding to Hb in response to anemia, hypoxia, and high altitude

102
Q

What does deficiency of G6PD cause?

A

RBCs more vulnerable to oxidant damage

Usually causes intermittent, severe intravascular hemolysis

103
Q

What are Heinz Bodies?

A

Irregularly contracted cells due to oxidant damage to the cell membrane and Hb

POM (4 decks)

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