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CAPS 301 T1 > Blood & Body Fluids Facts > Flashcards

Blood & Body Fluids Facts Flashcards

1
Q

Where do thrombin and vWf come from in the platelet adhesion step of platelet plug formation in haemostasis?

A

Thrombin: coagulation cascade (feedback)
vWf: megakaryocytes, endothelial cells, platelets

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2
Q

What are the components of tenase?

A

VIIIa, IXa, Ca++

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3
Q

How does Protein C, and its cofactor Protein S, prevent unnecessary coagulation?

A

Target Va and VIIIa to prevent clot formation (Va: forms prothrombinase; VIIIa: forms tenase)

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4
Q

Total Transcellular fluid volume in typical adult human

A

negligible

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5
Q

How are thromboxane A and prostacyclin (PGI2) synthesized? (main enzymes and intermediates)

A

From Phospholipids
Via phospholipase
To Prostaglantin H2 (PGH2)
To thromboxane A (damaged cells) or prostacyclin (intact cells)

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6
Q

Describe the characteristics of the Intrinsic Pathway of blood coagulation & clot formation in haemostasis.

A

Ongoing during tissue regeneration

Uses components that are in the blood, or have precursors in the blood

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7
Q

Name the 7 types of plasma proteins

A 
Albumin
Lipoproteins
Glycoproteins
Coagulation Factors
Immunoglobins
Complements
Hormones
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8
Q

How does low tissue O2 affect erythropoiesis?

A

signals to kidney to incr. EPO release, which stimulates erythropoiesis, increasing tissue O2

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9
Q

What role does prothrombinase play in the Common Pathway of blood coagulation & clot formation in haemostasis?

A

Activates Prothrombin -> Thrombin

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10
Q

Protein content level of ICF

A

High

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11
Q

What effect does ADP release have on cells adjacent to an injured site in a blood vessel?

A

Causes release of prostacyclin (prostaglandin inhibiting platelet aggregation) and NO (vasodilator)

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12
Q

Which factor targets Ca++ to prevent unnecessary coagulation?

A

Ca++ chelators

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13
Q

Why does haematopoietic activity of femur & tibia bone marrow fall off sharply during childhood?

A

Bones need the density for growth; pass duties to bones that grow less

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14
Q

What type of coagulation defect causes a defiency in prothrombin, VII, IX, X?

A

Vitamin K deficiency

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15
Q

What role does plasmin play in haemostasis?

A

Fibrinolysis:

Stable fibrin -> soluble fragments

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16
Q

What causes haemophilia?

A

Inherited

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17
Q

Describe platelet adhesion during platelet plug formation in haemostasis.

A
  • Glycoproteins constitutively expressed on endothelial and subendothelial cells
  • Adhesion factor (thrombin, integrin, vWf) release by subendothelial cells
    => Platelets bind exposed collagen & each other
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18
Q

What are the three biological phases of haemostasis?

A
  1. Initiation - Extrinsic pathway makes thrombin
  2. Amplification - Thrombin action: platelet activation, ^ prothrombinase activity, ^ tenase formation
  3. Propagation - Distal sites enhance tenase formation
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19
Q

What is involved in the platelet aggregation step of platelet plug formation in haemostasis?

A

Platelet activation promotes aggregation; ADP & fibrinogen key to forming unstable platelet plug

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20
Q

What are the components of prothrombinase?

A

Va, Xa, Ca++

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21
Q

Haemostasis is an integrated system. What causes Haemostasis?

A

Platelet plug formation

Clot formation

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22
Q

Which physical factor prevents unnecessary coagulation, and how?

A

Blood vessel integrity: -ve glycocalyx prevents -ve platelet adhesion

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23
Q

Which factor targets IXa (only) to prevent unnecessary coagulation?

A

alpha-Protease inhibitor

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24
Q

Which bones’ marrow play a key role in haematopoiesis as people age?

A

Vertebrae, ribs, sternum, pelvis

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25
Q

How do heparin and heparan sulphate prevent unnecessary coagulation in vivo?

A

Stimulate AT III (antithrombin III)

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26
Q

What happens to fibrinogen in the Common Pathway of blood coagulation & clot formation in haemostasis?

A

Hydrolyzed by thrombin to fibrin monomers and fibrinopeptides
Spontaneously polymeryzes to fibrin polymers

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27
Q

Which clotting factors are not produced sufficiently when there is a Vitamin K deficiency?

A

prothrombin, VII, IX, X

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28
Q

Which factor targets the TF.VIIa.Ca++ complex to prevent unnecessary coagulation?

A

Tissue factor pathway inhibitor (TFPI)

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29
Q

Major anion(s) in ECF: ISF

A

Cl-

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30
Q

What type of stem cells do pluripotent stem cells become if they are going to become thrombocyte?

A

Myeloid

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31
Q

Types of Granulocytes

A

Basophil
Neutrophil
Eosinophil

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32
Q

What happens to monocytes once they mature?

A

They enter the reticuloendothelial system:

  • enter tissue and stays (becomes “fixed macrophage”)
  • signal
  • breaks off (becomes “mobile macrophage”)
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33
Q

What role does XIIIa play in the Common Pathway of blood coagulation & clot formation in haemostasis?

A

Stabilizes cross-links between fibrin polymers in the clot

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34
Q

In which pathways of Haematopoiesis is Erythropoietin involved?

A

Myeloid Stem Cell growth into Erythrocytes & Thrombocytes

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35
Q

Which factors do PAI1 and PAI2 act on?

A

t-PA, u-PA

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36
Q

What results from a IX deficiency?

A

Type B haemophilia (coagulation defect)

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37
Q

Total body fluid volume in normal adult human

A

42L

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38
Q

What role does TF play in the Extrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

Binds and non-proteolytically activates VII;

Acts with VIIa and Ca++ to convert X->Xa (proteolytically)

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39
Q

Which factor increases blood flow & prevents platelet aggregation/adhesion/activation & causes vasodilation to prevent unnecessary coagulation?

A

Endothelial PGI2 (prostacyclin)

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40
Q

How does alpha-Protease Inhibitor prevent unnecessary coagulation?

A

Targets IXa (forms Tenase)

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41
Q

Name the 6 main regulators of erythropoiesis

A
  1. Tissue O2 levels
  2. EPO
  3. Cytokines (GM-CSF, IL-3)
  4. Iron & copper
  5. Folic acid & Vitamin B12
  6. Sex steroids
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42
Q

What are the 4 events that occur during formation of a platelet plug in haemostasis?

A

(“4 PAs”)

a. Platelet Adhesion
b. Platelet Activation
c. Platelet Aggregation
d. Primary arrest of bleeding

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43
Q

Typical erythrocyte life span, and reason

A

120 days; can’t synthesize protein & hemoglobin gets oxidized

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44
Q

What happens to fibrin polymers in the Common Pathway of blood coagulation & clot formation in haemostasis?

A

They are stabilized with cross-linkages, catalyzed by XIIIa

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45
Q

What happens to iron in erythrocytes?

A

Recycled: Macrophage breaks down erythrocyte and release Fe2+ back to plasma to be re-oxidized by Caeruloplasmin…

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46
Q

Haemostasis is an integrated system. What causes Clot formation?

A

Coagulation cascade

Platelet adhesion/activation/aggregation

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47
Q

What do platelets release from the alpha granules during the platelet activation step of platelet plug formation in haemostasis?

A

Thromboxane A (for platelet aggregation)
factor V (clotting factor)
fibrinogen (for platelet aggregation)
vWf (promotes platelet adhesion)

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48
Q

What does a macrophage break haemoglobin down into, and what happens to those components?

A
  • Globin -> amino acids; recycled
  • Iron -> back to blood & transferrin; recycled
  • Haem -> bilirubin -> in plasma -> albumin transports to liver -> bile -> secrete into intestine; excreted
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49
Q

What role do negative charges on activated platelets play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

Activate XII -> XIIa (slowly)

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50
Q

Total Plasma volume in typical adult human

A

3L

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51
Q

How does EPO affect erythropoiesis?

A

Prohibits BFU-E, CFU-E apoptosis (particularly CFU-E)

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52
Q

What are the components of the complex that activates X in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis? Does it have a name?

A

VIIIa, IXa, Ca++

Name: Tenase

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53
Q

How is blood volume calculated (from known plasma volume)?

A
  1. Use centrifugation to calculate % haematocrit, % plasma

2. V_blood = V_plasma / %plasma

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54
Q

Describe the Intrinsic Pathway of blood coagulation & clot formation in haemostasis.

A
  • Slow conversion of XII->XIIa by contact with negative charges on activated platelets; cofactor: High Molecular Weight Kininogen (HMWK)
  • XIIa feedsback to activation: stimulates prekallikrein->kallikrein, kallikrein proteolytically converts XII->XIIa
  • XIIa.HMWK converts XI->XIa.HMWK
  • XIa.HMWK converts IX->IXa
  • (separately) vWf releases VIII
  • thrombin converts VIII->VIIIa
  • VIIIa.IXa.Ca++ (“tenase”) converts X->Xa
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55
Q

Name the four roles of thrombin in haemostasis.

A
  1. enhance platelet aggregation
  2. Hydrolyze fibrinogen -> fibrin monomers & fibrinopeptides
  3. Convert XIII -> XIIIa
  4. Feedback (+) to increase production of VIIIa (-> tenase), Va (-> prothrombinase)
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56
Q

Major anion(s) in ECF: plasma

A

Cl-

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57
Q

Generally describe the process of haem synthesis

A

Porphyrins are synthesized/transformed in the mitochondria & cytoplasm, and eventually bind Fe2+ in the mitochondria to form haem

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58
Q

Shape of erythrocytes, and reason

A

Deformable biconcave disk; high SA:volume ratio for gas exchange, deformable to fit through capillaries

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59
Q

What is involved with the Humoral Substance Release portion of Vasoconstriction in haemostasis?

A

Serotonin (vasoconstrictor) is released by platelets or as a result of coagulation

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60
Q

Two main compartments of body fluids in humans & %

A

ICF (67%)

ECF (33%)

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61
Q

What is involved in the Platelet Activation step of platelet plug formation in haemostasis?

A
  • Platelets form pseudopodia
  • Platelets release materials in dense granules (Ca++, ATP, serotonin, ADP)
  • Platelets release materials in alpha granules (thromboxane A, factor V, fibrinogen, vWf)

** are linked

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62
Q

Which organs are hematopoietic, and when?

A

Yolk sac: early fetal development
Liver/spleen: mid-fetal development
Bone marrow: begins in mid-fetal development (4mo), decreases quickly in tibia & femur; decreases slowly in vertebrae/ribs/sternum/pelvis

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63
Q

2 main functions of blood & body fluids

A

Transport, Protection

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64
Q

What does bone marrow contain that allows it to be haematopoietic?

A

Pluripotent stem cells - can become erythrocytes, leukocytes, or thrombocytes

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65
Q

How does Endothelial NO prevent unnecessary coagulation?

A

Prevents platelet adhesion & aggregation

Vasodilator

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66
Q

Protein content level of ECF: plasma

A

medium

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67
Q

What two compounds act as vasodilators to prevent unnecessary coagulation in intact blood vessels?

A
  1. Endothelial PGI2 (prostacyclin)

2. Endothelial NO

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68
Q

What type of stem cells do pluripotent stem cells become if they are going to become monocytes?

A

Myeloid

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69
Q

How does GM-CSF/IL-3 affect erythropoiesis?

A

Promote erythrocyte development from precursors

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70
Q

Blood components

A 
Plasma
Formed Elements
   RBCs (Erythrocytes)
   WBCs (Leukocytes)
   Platelets (Thrombocytes)
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71
Q

What happens to mature erythrocytes (after forming from reticulocytes)?

A

Released from bone marrow, mature in 1-2 days

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72
Q

Name the three types of glycoproteins in the plasma

A

Transferrin
Haptoglobins
Caeruloplasmin

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73
Q

Describe the general process of erythrocyte breakdown by the reticuloendothelial system

A

Mobile macrophage takes up erythrocyte & breaks down membrane and haemoglobin

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74
Q

What is PAI-2 and what does it do?

A

Placental Plasminogen Activator Inhibitor; prevents plasminogen -> plasmin

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75
Q

What processes are involved in blood coagulation & clot formation in haemostasis?

A

Extrinsic Pathway, Intrinsic Pathway, Common Pathway

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76
Q

Name three Ca++ chelators

A

Oxalate, EDTA, Citrate

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77
Q

Which factor targets Va and VIIa to prevent unnecessary coagulation?

A

Protein C and its cofactor, Protein S

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78
Q

Transport pathway for nutrients in body fluids

A

Capillaries -> Interstitial fluid -> ICF

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79
Q

Describe the Storage step of iron metabolism

A

Excess iron is incorporated into ferritin, which is stored in the liver

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80
Q

Erythrocytes: nucleus?

A

no

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81
Q

What roles does XIIa.HMWK play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

Feedback on prekallikrein -> kallikrein, to make more XIIa.HMWK
Activate XI -> XIa.HMWK

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82
Q

What are the two events that occur during Vasoconstriction in haemostasis?

A
  1. Local contraction

2. Humoral substance release

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83
Q

How do iron and copper affect erythropoiesis?

A

Iron helps form haem, copper helps caeruloplasmin oxidize Fe2+ -> Fe3+

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84
Q

Characteristics of Reticulocyte

A

Loses nucleus

Only a few ribosomes & Golgi remnants left in cytoplasm

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85
Q

Which plasma proteins are involved with maintaining osmotic pressure?

A

Albumin

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86
Q

What type of stem cells do pluripotent stem cells become if they are going to become Lymphocyte?

A

Lymphoid

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87
Q

How does a clot form in haemostasis?

A

Fibrin lattice traps erythrocytes, leukocytes

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88
Q

Name 2 characteristics of erythrocytes related to CO2 transport

A

High [carbonic anhydrase] to convert CO2 -> HCO3-

High anion permeability to allow Cl-, HCO3- exchange

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89
Q

Total ICF volume in typical adult human

A

28L

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90
Q

Describe thrombocytes, in terms of shape, nucleus, and membrane

A

Disk-shaped, but can changed w/ pseudopodia
No nucleus
Have “fuzzy” glycocalyx (negatively charged)

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91
Q

Roles of blood & body fluids in transport (5)

A

“RENCH”

Respiration (O2, CO2)
Excretion (waste to kidneys, intestines, lungs)
Nutrients (from gut to tissues; between organs)
Communication (hormones)
Homeostasis (water & control hormones)

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92
Q

What role does VIIa play in the Extrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

Combines with TF, Ca++ to convert X->Xa

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93
Q

What are the attendant ions for Na+, and where are they used?

A

Cl-, HCO3-; in ECF

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94
Q

What do platelets release from the dense granules during the activation step of platelet plug formation in haemostasis?

A

Ca++, ADP, ATP, serotonin

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95
Q

Types of Leukocytes

A 
Lympocytes
Granulocytes
   Basophil
   Neutrophil
   Eosinophil
Monocytes
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96
Q

Describe the structure of haemoglobin

A

4 polypeptide (globin) chains: 2 alpha, 2 ß
Each globin chain holds 1 haem molecule in the middle (4 haem total)
Each haem molecule has 1 Fe2+ ion in the center, which binds 1 molecule O2 (4 O2 total)

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97
Q

Which factors are involved with the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A 
vWf
VIIIa
kallikrein (prekallikrein)
XIIa.HMWK
XIa.HMWK
IXa
Ca++
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98
Q

Function of albumin in plasma

A

Maintain oncotic pressure, bind/transport drugs & other molecules

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99
Q

Describe a senescent erythrocyte

A

Decreased membrane continuity
Decreased enzyme activity
Increased [methaemoglobin] (oxidized Hb)

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100
Q

Describe clot retraction in haemostasis and the result.

A

Serum oozes out of fibrin lattice (erythrocytes, leukocytes trapped), bringing the tissue edges together for repair

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101
Q

In which pathways of Haematopoiesis is G-CSF involved?

A

Myeloid Stem Cell growth into Granulocytes

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102
Q

Which factor breaks down stable fibrin into soluble fragments?

A

Plasmin

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103
Q

How are thrombocytes formed, and what factor is involved?

A

Fragments that peel off megakaryocytes in marrow; stimulated by liver release of thrombopoietin, which increases megakaryocyte synthesis

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104
Q

Transport pathway for wastes in body fluids

A

ICF -> ISF -> lymph/blood capillaries

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105
Q

How do folic acid & Vitamin B12 affect erythropoiesis?

A

Act as cofactors for erythropoietic enzymes

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106
Q

What type of stem cells do pluripotent stem cells become if they are going to become granulocytes?

A

Myeloid

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107
Q

Major cation(s) in ECF: ISF

A

Na+

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108
Q

Describe the (Reduction &) Incorporation step of iron metabolism

A

Reduce Fe3+ to Fe2+, incorporate it into haem in mitochondria, and then incorporate haem into haemoglobin in the cytoplasm

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109
Q

Describe the mechanism of vasoconstriction in haemostasis

A

Initial neurogenic spasm (~60s), then myogenic spasm (~20-30min)

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110
Q

Which types of plasma proteins are involved with the plasma Immune system?

A

Immunoglobins, complements

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111
Q

What initially activates XII in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

Contact with negative charges on the activated platelets

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112
Q

Which 6 compounds/classes act as in vivo anticoagulants?

A
  1. Antithrombin III (AT III)
  2. Heparin & Heparan sulphate
  3. Tissue factor pathway Inhibitor (TFPI)
  4. Thrombomodulin
  5. alpha-protease inhibitor
  6. Protein C and co-factor, Protein S
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113
Q

Units of solute concentration & their relation

A
  • mmol/L
  • meq/L (mmol/L x z; z=valence)
  • mosmol/kg H2O (# of osmotically active solutes x mmol/kg H2O)
  • mosmol/L H2O (# of osmotically active solutes x mmol/L H2O)
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114
Q

Characteristics of Late erythroblast

A

Nucleus & cytoplasm shrinking

Rapid Hb synthesis until almost all is present

115
Q

Which 5 factors are key in haematopoiesis, in the Myeloid Stem Cell path?

A
  1. Erythropoietin (EPO)
  2. Granulocyte Colony Stimulating Factor (G-CSF)
  3. Macrophage Colony Stimulating Factor (M-CSF)
  4. Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF)
  5. Interleukin-3 (IL-3)
116
Q

Major cation in ICF

117
Q

How does heparin prevent unnecessary coagulation in vitro?

A

Stimulates AT III (antithrombinase III) action

118
Q

Result of dehydration, in terms of haematocrit

A

Increases to 70% BECAUSE OF DECREASE IN PLASMA VOLUME (same absolute volume of haematocrit)

119
Q

Role of hemoglobin

A

Carry O2, CO2; act as main buffer in blood

120
Q

Describe sickle cell anemia

A

Synthesize Haemoglobin S instead of alpha, ß globulins => decrease O2 carrying ability (anemia)

121
Q

Difference between solute concentration in plasma and plasma water

A

In “plasma water” doesn’t include the volume of the solutes in plasma (which is ~7% by volume), so [ ] in plasma water is greater than [ ] in plasma

122
Q

What are the components of the complex that activates X in the Extrinsic Pathway of blood coagulation & clot formation in haemostasis? Does it have a name?

A

TF, VIIa, Ca++

No name

123
Q

Components of ECF & %

A

ISF (75%)
Plasma (20%)
Transcellular Fluid (5%)

124
Q

What is t-PA?

A

(endothelial) Tissue-type Plasminogen Activator

125
Q

Describe the effect of a Vitamin K deficiency

A

Inadequate production of several clotting factors: prothrombin, VII, IX, X

126
Q

Role of Cl- and HCO3- in ECF

A

Attendant ions to Na+ - maintain electrical neutrality

127
Q

What activates XII in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis (once process starts)?

A

Kallikrein; proteolytic

+ve feedback on kallikrein production by XIIa

128
Q

How does Tissue Factor Pathway Inhibitor (TFPI) prevent unnecessary coagulation?

A

Targets TF.VIIa.Ca++ complex (intrinsic pathway)

129
Q

Function of Hormones in plasma

A

Physiological regulation

130
Q

How is haemoglobin synthesized?

A

From haem (x4), globin chains (alpha x2, ßx2); in cytoplasm

131
Q

Which factor stimulates AT III activity to prevent unnecessary coagulation in vitro?

132
Q

Describe the Common Pathway

A
  • Thrombin (circulating) activates V->Va
  • Va, Xa (Intrinsic/Extrinsic path), Ca++ form complex = Prothrombinase
  • Prothrombinase activates prothrombin -> thrombin
  • Thrombin feeds back (+) to first step (incr. Va, incr prothrombinase, incr thrombin)
  • Thrombin hydrolytically cleaves fibrinogen -> fibrin monomers and fibrinopeptides
  • Spontaneous polymerization to fibrin polymers
  • Thrombin activates XIII -> XIIIa
  • XIIIa catalyzes formation of fibrin lattice
133
Q

Characteristics of Early erythroblast

A

Large
Nucleated
Rapid Hb synthesis

134
Q

Which factors/proteins are involved with fibrinolysis?

A

t-PA, u-PA; inhibited by PAI-1, PAI-2; plasminogen, plasmin

135
Q

Major anion(s) in ICF

A

phosphates, proteins

136
Q

How does endothelial PGI2 prevent unnecessary coagulation?

A

(PGI2 = prostacyclin)
Increases blood flow to prevent platelet activation
Prevents platelet adhesion & aggregation
Vasodilator

137
Q

Name the 6 main functions of plasma proteins

A

“ITH OVA!”

(plasma) Immune system
Transport
Hormones

Osmotic pressure maintenance
(blood) Viscosity maintenance
Acid-base equilibrium

138
Q

What does a Late Erythroblast become, in the process of erythropoiesis?

A

Reticulocyte

139
Q

How do sex steroids affect erythropoiesis?

A

Testosterone: promotes
Estrogen: inhibits

140
Q

Characteristics of fibrin clot

A

Stable, cross-linked lattice

141
Q

What is the goal of the Extrinsic and Intrinsic Pathways of blood coagulation & clot formation in haemostasis?

A

Conversion of X -> Xa for the common pathway

142
Q

Which plasma proteins are involved with transport?

A

Albumin, lipoproteins, glycoproteins

143
Q

Describe the uptake step of iron metabolism

A

Receptor-mediated endocytosis takes Fe3+ from transferrin into the bone marrow

144
Q

What stimulates prokallikrein activation in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

XIIa (+ve feedback, since prokallikrein -> kallikrein, kallikrein catalyzes XII -> XIIa)

145
Q

Which factors are involved in forming Lymphocytes from pluripotent stem cells?

A

None (of the ones we studied)

146
Q

Haemostasis is an integrated system. What does vessel damage instigate?

A

Vasoconstriction, Platelet Adhesion/Activation/Aggregation, Coagulation Cascade

147
Q

What type of stem cells do pluripotent stem cells become if they are going to become erythrocytes?

148
Q

Which 2 compounds act as in vitro anticoagulants?

A
  1. Heparin

2. Ca++ Chelators: EDTA, Oxalate, Citrate

149
Q

What is the goal of the Common Pathway?

A

Formation of a stable fibrin clot

150
Q

Total ECF volume in typical adult human

151
Q

Describe von Willebrand disease

A

VIII/vWf deficiency -> poor platelet adhesion -> internal bleeding

152
Q

Cause of haemolysis

A

Placing cell in hypotonic solution -> water moves into cell

153
Q

What disease results from a platelet deficiency?

A

Thrombocytopaenia -> don’t clot properly

154
Q

Protein content level of ECF: ISF

155
Q

What results from a deficiency of VIII?

A

Type A haemophilia (coagulation defect)

156
Q

What happens in the platelet membrane during the aggregation step of platelet plug formation in haemostasis?

A

Negatively-charged phospholipids translocate to the outside of the membrane

157
Q

What role does Ca++ play in the Extrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

Combines with TF.VIIa to form the TF.VIIa.Ca++ complex

Activates X -> Xa

158
Q

What is u-PA?

A

(plasma) Urokinase-type Plasminogen Activator

159
Q

Which steps of erythropoiesis involve cytokines?

A

Formation of BFU-E, CFU-E, Proerythroblasts

160
Q

Describe the Transport step of iron metabolism

A

Transferrin binds 2 Fe3+

161
Q

What is an excess of platelets called?

A

Thrombocytosis

162
Q

Haemostasis is an integrated system. What does Vasoconstriction instigate?

A

Platelet Adhesion/Activation/Aggregation

163
Q

Main source of EPO in adults

A

Kidneys (peritubular interstitial cells)

164
Q

What activates V in the Common Pathway of blood coagulation & clot formation in haemostasis?

A

Thrombin (circulating)

165
Q

What are the three classes of anticoagulants in intact blood vessels?

A
  1. Physical factors
  2. Vasodilators
  3. Anticoagulants
166
Q

Which factors are involved in forming Thrombocytes from pluripotent stem cells?

A

EPO, GM-CSF, IL-3

167
Q

Which factor acts as a vasodilator & prevents platelet adhesion/aggregation to prevent unnecessary coagulation?

A

Endothelial NO

168
Q

Which body fluid compartment(s) has/have K+ as the major cation?

169
Q

How do Ca++ chelators prevent unnecessary coagulation?

A

Remove Ca++ (can’t form protease complexes: TF.VIIa.Ca++, VIIIa.IXa.Ca++, Va.Xa.Ca++ from Extr, Intr, Comm pathways resp)

170
Q

How are anions and cations related in body fluid?

A

[cations]=[anions] in meq/L (using valence)

171
Q

Normal thrombocyte concentration

A

250 000/mm^3

172
Q

In which pathways of Haematopoiesis is M-CSF involved?

A

Myeloid stem cell growth in monocytes

173
Q

What activates prothrombin in the Common Pathway of blood coagulation & clot formation in haemostasis?

A

Prothrombinase

174
Q

What role does XIa.HMWK play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

Activates IX -> IXa

175
Q

Major cation(s) in ECF: plasma

176
Q

What results from a VIII/vWf deficiency?

A

von Willebrand disease (coagulation defect)

177
Q

What do platelets contain? (granule types)

A

Dense granules, and alpha granules

178
Q

Name the three types of coagulation defects

A
  1. Vitamin K deficiency
  2. Haemophilia
  3. von Willebrand disease
179
Q

What is the cofactor for conversion of XII -> XIIa in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

High Molecular Weight Kininogen (HMWK)

180
Q

How is plasma volume measured?

A
  1. Inject known amt of dye/* of known conc. that will ONLY spread in plasma (e.g. attach to albumin)
  2. Let equilibrate
  3. Draw blood sample and measure dye/* conc.
  4. Use CiVi = CfVf => Vf = Ci/Cf * Vi to get plasma volume
181
Q

Which factors are involved in forming Monocytes from pluripotent stem cells?

A

M-CSF, GM-CSF, IL-3

182
Q

Describe the oxidation step of iron metabolism

A

Caeruloplasmin (uses Cu) oxidizes Fe2+ -> Fe3+

183
Q

Protein content of body fluid compartments, from highest to lowest

A

ICF > ECF: plasma > ECF: ISF

184
Q

How does AT III prevent unnecessary coagulation?

A

(AT III: Antithrombin III)

Targets thrombin, IXa, Xa

185
Q

Function of lipoproteins in plasma

A

Transport lipids

186
Q

What does a Reticulocyte become, in the process of erythropoiesis?

A

Erythrocyte

187
Q

Total ISF volume in typical adult human

A

Interstitial fluid; 10.5L

188
Q

What does a Burst Forming Unit Erythroid (BFU-E) become, in the process of erythropoiesis?

A

Colony Forming Unit Erythroid (CFU-E)

189
Q

Which factors target complexes to prevent unnecessary coagulation?

A

TFPI (TF.VIIa.Ca++)
Protein C w/cofactor Protein S (Va -> Va.Xa.Ca++; VIIIa -> VIIIa.IXa.Ca++)
alpha-Protease Inhibitor (IXa -> VIIIa.IXa.Ca++)
AT III (IXa -> VIIIa.IXa.Ca++; Xa -> Va.Xa.Ca++)

190
Q

What is tenase, and which pathway is it used in?

A

VIIIa.IXa.Ca++, intrinsic

191
Q

Which body fluid compartment(s) has/have Na+ as the major cation?

A

ECF: plasma & ISF

192
Q

Which anticoagulation factor(s) activate(s) AT III?

A

(AT III: Antithrombin III)

Heparin (in vivo & in vitro), heparan sulphate (in vivo only)

193
Q

Main source of EPO (fetus)

194
Q

Result of polycythemia, in terms of haematocrit

A

Increase to ~70% (instead of normal 40-45%)

195
Q

What role does Ca++ play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

Combines with VIIIa, IXa to form tenase

Activates X->Xa

196
Q

In which pathways of Haematopoiesis is GM-CSF involved?

A

Myeloid stem cell growth into all derivatives: erythrocytes, thrombocytes, granulocytes, monocytes

197
Q

Which body fluid compartment(s) has/have proteins & phosphate as the major anions?

198
Q

Cause of crenation

A

Placing cell in hypertonic solution -> water moves out

199
Q

What are the components of prothrombinase?

A

Va, Xa, Ca++

200
Q

Describe Thalassemias and their cause

A

inherited; reduced/absent synthesis of one or more globin chains => no haemoglobin

201
Q

How are plasma proteins involved with maintaining acid-base equilibrium?

A

Uptake/conversion of CO2/HCO3-/H2CO3 in respiration

202
Q

Haemostasis is an integrated system. What does Platelet Adhesion/Activation/Aggregation instigate?

A

Coagulation Cascade (mutual positive feedback)
Platelet Plug Formation
Clot Formation

203
Q

Roles of blood & body fluids in protection (2)

A 
Haemostasis (platelet aggregation, blood coagulation)
Immune Reactions (plasma & blood cells)
204
Q

What does a pluripotent stem cell become, in the process of erythropoiesis?

A

Burst Forming Unit Erythroid (BFU-E)

205
Q

What activates XI in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

206
Q

Which factors are involved in forming granulocytes from pluripotent stem cells?

A

G-CSF, GM-CSF, IL-3

207
Q

What are the two types of Haemophilia?

A

Type A: VIII deficiency
Type B: IX deficiency
(missing coagulation factors)

208
Q

What do platelets store in dense granules?

A

Ca++, ADP, ATP, serotonin

209
Q

What does a Colony Forming Unit Erythroid (CFU-E) become, in the process of erythropoiesis?

A

Proerythroblast

210
Q

Which factors are involved with the extrinsic pathway?

A

Tissue factor, VII->VIIa, X->Xa

211
Q

Which factor is common to the Extrinsic and Intrinsic Pathways?

212
Q

Function of complements in plasma

A

Immune response

213
Q

What are the causes of hyperfibrinolysis?

A

Genetic or acquired

214
Q

What activates X in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

VIIIa.IXa.Ca++ (Tenase)

215
Q

Normal erythrocyte concentration

A

5million/mm^3

216
Q

What causes von Willebrand disease?

A

Inherited VIII/vWf deficiency

217
Q

Function of transferrin in plasma

A

Bind & transport Fe3+

218
Q

Which factors target thrombin to prevent unnecessary coagulation?

A

Antithrombin III, Thrombomodulin

219
Q

Which factor uses physical means to prevent unnecessary coagulation?

A

Intact smooth endothelial lining (-ve glycocalyx on lining and on platelets repel, preventing adhesion)

220
Q

Negatively-charged phospholipids translocate to the outer platelet membrane during aggregation. What effect does this have during blood coagulation & clot formation in haemostasis?

A

Initiates coagulation cascade
Platelet autolysis forms fibrin
Clot forms
… eventually, fibrinolysis

221
Q

Describe the cause of a Vitamin K deficiency

A

Antibiotic inhibits bacterial production of Vitamin K

222
Q

Normal plasma %

223
Q

Describe the absorption step of iron metabolism

A

Fe2+ absorbed from gut, into plasma

224
Q

What activates IX in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

225
Q

What is the source of Xa in prothrombinase?

A

Intrinsic/Extrinsic Pathway

226
Q

Stages/formations of erythropoiesis

A 
Pluripotent Stem Cell
Burst Forming Unit Erythroid (BFU-E)
Colony Forming Unit Erythroid (CFU-E)
Proerythroblast
Early Erythroblast
Late Erythroblast
Reticulocyte
Erythrocyte (mature)
227
Q

What is PAI-1 and what does it do?

A

endothelial tissue Plasminogen Activator Inhibitor; prevents plasminogen -> plasmin

228
Q

What is a platelet deficiency called?

A

Thrombocytopaenia

229
Q

In which pathways of Haematopoiesis is IL-3 involved?

A

Myeloid stem cell growth into all derivatives: erythrocytes, thrombocytes, granulocytes, monocytes

230
Q

Describe hyperfibrinolysis

A

PAI-1 deficiency -> dissolve clots immediately -> no haemostasis (like haemophilia)

231
Q

Haemostasis is an integrated system. What does Clot formation instigate?

A

Haemostasis

232
Q

Name the three diseases related to haemoglobin

A
  1. Porphyrias
  2. Thalassemias
  3. Sickle Cell (Anemia)
233
Q

Describe the characteristics of the extrinsic pathway

A

Activated immediately
Uses non-circulating components
Goal: Convert X -> Xa for the Common Pathway

234
Q

How are the zymogens of most proteins involved with haemostasis activated, and what do most of the proteins do?

A

Proteolytic cleavage; act as proteases for the next zymogen

235
Q

Which factor targets thrombin (only) to prevent unnecessary coagulation?

A

Thrombomodulin

236
Q

Which factors target IXa to prevent unnecessary coagulation?

A

AT III, alpha-protease inhibitor

237
Q

What are the functions of the factors that platelets store in alpha granules?

A

Adhesion factor, coagulation factor, platelet-derived growth factor

238
Q

Describe the causes of vascular defects

A

Congenital or acquired

239
Q

What activates XIII in the Common Pathway of blood coagulation & clot formation in haemostasis?

240
Q

What role does thrombin play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

Activates VIII (released from vWf) -> VIIIa

241
Q

What disease results from an excess of platelets?

A

Thrombocytosis (platelet abnormality) -> clot too easily

242
Q

Describe the two types of platelet abnormalities & their phenotypes

A

thrombocytopaenia - deficiency, no clotting

thrombocytosis - excess, too much clotting

243
Q

Normal % haematocrit

244
Q

Haemostasis is an integrated system. What does the coagulation cascade instigate?

A

Platelet Adhesion/Activation/Aggregation (mutual positive feedback)
Clot formation

245
Q

Function of Immunoglobins in plasma

A

Immune response

246
Q

What stabilizes the fibrin cross-links in the Common Pathway of blood coagulation & clot formation in haemostasis?

247
Q

What is the goal of blood coagulation & clot formation in haemostasis?

A

Digest fibrinogen with thrombin, to form (stable, insoluble) fibrin

248
Q

How do intact blood vessels physically prevent unnecessary coagulation?

A

Negatively charged glycocalyx on both smooth endothelial lining and platelets -> prevents adhesion

249
Q

Purpose of haemostasis

A

Seal injured blood vessel, maintain blood fluidity, and dissolve clot after coagulation

250
Q

Function of haptoglobins in plasma

A

Bind free Haemoglobin to prevent excretion

251
Q

Which factor targets thrombin, IXa, Xa to prevent unnecessary coagulation?

A

Antithrombin III (AT III)

252
Q

What process are t-PA and u-PA involved in, and what is their role?

A

Fibrinolysis

Activate plasminogen -> plasmin

253
Q

What role does Va play in the Common Pathway of blood coagulation & clot formation in haemostasis?

A

Complexes with Xa, Ca++ to form Prothrombinase

Activates Prothrombin -> Thrombin

254
Q

Haemostasis is an integrated system. What causes Vasoconstriction?

A

Vessel damage

255
Q

What role does VIIIa play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

Combines with IXa, Ca++ to form tenase

Activates X->Xa

256
Q

How does Thrombomodulin prevent unnecessary coagulation?

A

Targets thrombin

257
Q

Describe the process of the Extrinsic Pathway of blood coagulation & clot formation in haemostasis.

A
  • Tissue Factor (expressed on vascular membrane) is exposed
  • TF acts as VII receptor, NON-PROTEOLYTIC activator to VIIa
  • TF.VIIa binds Ca++ from activated platelets
  • TF.VIIa.Ca++ complex: proteolytic X -> Xa
258
Q

Haemostasis is an integrated system. What causes Platelet Plug formation?

A

Platelet Adhesion/Activation/Aggregation

259
Q

What disease results from a PAI-1 deficiency?

A

Hyperfibrinolysis (dissolve clots too easily)

260
Q

Name the 6 steps in Iron Metabolism

A
  1. Absorption
  2. Oxidation
  3. Transport
  4. Uptake
  5. (Reduction &) Incorporation
  6. Storage
261
Q

Name the four types of haemostatic disorders

A
  1. Vascular defect
  2. Platelet abnormalities
  3. Hyperfibrinolysis
  4. Coagulation defects
262
Q

Result of anemia, in terms of haematocrit

A

Decreases to 15-30% (instead of 40-45%)

263
Q

Which factor is usually carried by von Willebrand factor?

264
Q

What role does thrombin play in the Common Pathway of blood coagulation & clot formation in haemostasis?

A

Activates V -> Va (+ve feedback)
Activates XIII -> XIIIa
Hydrolyzes fibrinogen -> fibrinopeptides + fibrin monomers

265
Q

Which factor stimulates AT III action to prevent unnecessary coagulation in vivo?

A

Heparin and heparan sulphate

266
Q

Function of Caeruloplasmin in plasma

A

Bind Cu to catalyze Fe2+ oxidation to Fe3+

267
Q

Which structures prevent blood loss from an intact vessel?

A

Endothelium and Sub-endothelium (basement membrane)

268
Q

Haemostasis is an integrated system. What causes Platelet Adhesion/Activation/Aggregation?

A 
Vessel damage
Coagulation Cascade (mutual feedback)
Vasoconstriction
269
Q

Describe Porphyrias & its cause

A

Accumulation of porphyrins & precursors in liver and bone marrow => haem synthesis disorder

270
Q

Which factors target VIIa to prevent unnecessary coagulation?

A

TFPI (targets TF.VIIa.Ca++ complex)

271
Q

Which body fluid compartment(s) has/have Cl- as the major anion?

A

ECF: plasma & ISF

272
Q

What activates VII in the Extrinsic Pathway of blood coagulation & clot formation in haemostasis? Proteolytic?

A

Tissue Factor (on vascular membrane); non-proteolytic

273
Q

What activates VIII in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

Thrombin (from the common pathway)

274
Q

List the four main steps of haemostasis

A
  1. Vasoconstriction
  2. Formation of a platelet plug
  3. Blood coagulation & stable clot formation
  4. Clot retraction & fibrinolysis
275
Q

What role does Xa play in the Common Pathway of blood coagulation & clot formation in haemostasis?

A

Complexes with Va, Ca++ to form prothrombinase

Activates prothrombin -> thrombin

276
Q

What does a Proerythroblast become, in the process of erythropoiesis?

A

Early erythroblast

277
Q

What are the inhibitors of t-PA and u-PA called?

A

PAI-1, PAI-2 (Plasminogen Activator Inhibitor; 1 is from endothelial tissue, 2 is from placenta)

278
Q

How does VIII enter the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

Release from vWf, which carries it in blood

279
Q

Haemostasis is an integrated system. What causes the coagulation cascade?

A

Vessel damage

Platelet Adhesion/Activation/Aggregation (mutual feedback)

280
Q

What role does IXa play in the Intrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

Combines with VIIIa, Ca++ to form tenase

Activates X->Xa

281
Q

What activates X in the Extrinsic Pathway of blood coagulation & clot formation in haemostasis?

A

TF.VIIa.Ca++ complex (TF: tissue factor)

282
Q

Which factors are involved in forming erythrocytes from pluripotent stem cells?

A

EPO, GM-CSF, IL-3

283
Q

What does a Early erythroblast become, in the process of erythropoiesis?

A

Late Erythroblast

284
Q

What role does Ca++ play in the Common Pathway of blood coagulation & clot formation in haemostasis?

A

Complexes with Va, Xa to form prothrombinase

Activates prothrombin -> thrombin

CAPS 301 T1 (10 decks)

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