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PA10315 COPY > Blood > Flashcards

Blood Flashcards

1
Q

How much blood does an average human have?

A

5 litres.

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2
Q

What is the ideal pH range, osmolarity range and number of proteins found in the plasma

A
  1. pH=7.35-7.45.
  2. 285-295 mOsm
  3. proteins found in plasma>10,000 proteins
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3
Q

What are some of the roles of blood?

A
  1. Transport of oxygen, CO2, nutrients and excretory products;
  2. Regulation of the body in ways such as delivering hormones and diversion of blood in homeostasis
  3. Temperature control- protection such as the role of leukocytes in infection and clotting mechanisms to prevent blood loss
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4
Q

What is a hematocrit used for ?

A
  1. Rapid assessment of blood composition using centrifuging.

2. Percentage of blood volume that is composed of red blood cells

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5
Q

How are blood cells generated?

A
  1. The bone marrow - from hematopoietic stem cells.

2. These are undifferentiated cells capable of producing the precursors of different blood cells.

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6
Q

How do platelets look different from other types of blood cell?

A
  1. They are cell fragments and do not have a nucleus.
  2. They are also discoid shaped.
  3. Found in bone marrow
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7
Q

What is the production of platelets controlled by?

A
  1. Thrombopoietin - this is a hormone that is mainly produced by the liver and activates megakaryocytes
  2. Progenitor cells- megakaryocytes- cells with multilobed nucleus
  3. Activation of megakaryocytes stimulates platelet production.
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8
Q

How is the number of platelets in the blood regulated?

A
  1. If the platelet count is normal, the platelets will be bound to thrombopoietin.
  2. If the count is low, TPO (thrombopoietin) is free and unbound so more platelets can be produced.
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9
Q

How are platelets activated?

A
  1. If the epithelial layer is damaged, proteins underneath (including collagen and connective tissue) are exposed. 2. The platelets attach to the collagen and become activated.
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10
Q

What is thromboxane A2 and what does it do?

A
  1. It’s a signalling molecule that can feedback and activate more platelets.
  2. It can cause the platelets to aggregate - positive feedback.
  3. It also results in the contraction of vascular smooth muscle, resulting in vasoconstriction.
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11
Q

What benefit does platelets aggregating have?

A
  1. It creates a plug at the site of injury.

2. Attach to each other and spiky = activated

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12
Q

Give a summarised description of the platelet plug formation.

A
  1. Damage- altered endothelial cell (collagen exposed)
  2. Collagen is prothrombotic for platelets
  3. Platelets adhere to collagen primarily through a second protein von Willebrand factor (vWF)
  4. vWF forms a bridge between the damaged blood vessel and the circulating platelet
  5. Triggers platelet activation and the secretion of signalling molecules- Adenosine Diphosphate (ADP) and serotonin
  6. These rapidly activate the platelets that pass
  7. Activation and aggregation positive feedback mechanisms
  8. . After platelets bind to the collagen with vWF they change shape which causes them to be activated and release ADP and serotonin from electron dense granules- activates other platelets nearby
  9. Discharge of mediators- activate more platelets causes platelet plug to grow in size
  10. Chemical mediators and thromboxane act on blood vessel- contraction of vascular smooth muscle
  11. Then aggregation- fibrinogen receptors on surface of platelet enable them to bind to fibrinogen and allows platelets to bind together
  12. A low platelet count leads to bleeding disorder thrombocytopenia
  13. If part of the pathway leading to platelet activation is disrupted, then this can also lead to a bleeding disorder
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13
Q

What is erythropoiesis?

A

The formation of blood cells that happens in the bone marrow.

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14
Q

What is anaemia?

A
  1. The decreased ability to transport oxygen
  2. Due to a reduced number of RBCs/haemoglobin per RBC or both options.
  3. There may be a dietary deficiency of iron, bone marrow failure, poor production of EPO or increased destruction of RBCs, sickle cell
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15
Q

What are monocytes?

A
  1. Cells that can differentiate into a second cell type called a macrophage.
  2. They are the largest of the blood cells and have an irregular, often lobed nucleus.
  3. They contain 5 granules.
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16
Q

What do neutrophils look like?

A
  1. They have a distinct nucleus (not round) and they are lobular and granular.
  2. Have a distinct nucleus with 2-5 lobes
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17
Q

What are lymphocytes?

A
  1. Natural killer cells that lyse target cells.
  2. They have a large nucleus and a small number of granules with lysosomal enzymes
  3. Include B cells, T helpers and natural killer cells
  4. Provide protection against specific pathogens- adaptive immune system
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18
Q

What are basophils?

A
  1. They are involved in allergic reactions and contain granules of histamine and heparin.
  2. Degranulation occurs in allergic reactions such as urticaria (skin rash) & anaphylactic shock
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19
Q

What is eryhthropoietin and what does it do?

A
  1. It is a hematopoietic growth factor that stimulates the production of erythrocytes.
  2. Produced by kidney
  3. controls RBC production in the bone marrow
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20
Q

How are platelets formed from megakaryocytes?

And describe structure of megakaryocytes.

A
  1. They fragment into platelets.
  2. Have large surface area
  3. Lots of invaginations means shoots off platelets very quickly and easily
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21
Q

What are the two main stages in blood clotting?

A
  1. Primary haemostasis and secondary haemostasis.
  2. The plug is formed in primary and the plug is stabilised and transformed into a clot by a fibrin network in the second stage.
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22
Q

What is haemotoma?

A

The accumulation of blood in tissues - forms a bruise.

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23
Q

How do platelets adhere to collagen fibres?

A
  1. Via an intermediate protein called von Willebrand factor (vWF).
  2. It forms a bridge between the damaged blood vessel and the circulating platelet.
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24
Q

What are the three main steps in platelet action?

A
  1. Platelet activation
  2. platelet aggregation
  3. platelet plug formation.
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25
Q

What proteins are in platelets that enhance plug formation?

A
  1. Actin and myosin that can contract in activated platelets.
  2. A cytoskeleton that contract in activated to platelets to enhance plug formation.
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26
Q

How is the formation of the platelet plug prevented from spreading to the healthy body?

A
  1. Healthy endothelial cells synthesise Prostacyclin and nitric oxide.
  2. These are inhibitors of platelet activation/aggregation
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27
Q

How is a clot formed?

A
  1. Endothelial Cells coat the inside of blood vessels and in direct contact with blood
  2. Damage of endothelial cells exposes the subendothelial proteins formed by connective tissues collagen fibres
  3. Platelets adhere to these collagen fibres via an intermediate protein called von Willebrand factor (vWF)
  4. Adhesion of platelets to damaged surface
  5. Platelet activation, platelet Aggregation, platelet plug formation
  6. Cascade of enzymes that result in the activation of Thrombin.
  7. Thrombin cleaves fibrinogen into fibrin - these bind together to form a loose meshwork.
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28
Q

What does thrombin do?

A
  1. It is a protease enzyme that cleaves proteins - it cleaves fibrinogen to form fibrin.
29
Q

What is the extrinsic pathway?

A

The principle pathway that is activated in clotting. The factors needed to activate the pathway are outside of the blood.

30
Q

What is the intrinsic pathway?

A
  1. Major pathway activated?
  2. Everything required to activate the intrinsic cascade is found in the blood
  3. When damage inside vascular system
31
Q

What feeds back to the intrinsic pathway?

A
  1. Thrombin - it activates components in the intrinsic pathway to generate even more thrombin.
32
Q

Where does thrombin bind?

A

A site on the N terminus of the thrombin receptor (PAR - protease activated receptor).

33
Q

How is the blood clot dissolved?

A
  1. Tissue plasminogen activators are secreted by endothelial cells that cause plasminogen to be cleaved into plasmin (an enzyme)
  2. During clot formation – both plasminogen activators and plasminogen bind to fibrin and become incorporated into the clot
  3. Binding of tPA to fibrin is important as this increases the activity of the enzyme and tPA catalyses the conversion of plasminogen into plasmin
  4. Plasmin cleaves fibrin into soluble fibrin fragments
34
Q

What does this trigger

A

Release of Adp and serotonin

35
Q

What is platelet aggregation

A
  1. positive feedback
  2. attachment of platelets to each other recruits more platelets
  3. results in formation of a platelet plug
36
Q

What happens in platelet plug formation?

A
  1. Platelets bind to the sub-endothelial layer and become activated
  2. Activated platelets release the contents of secretory vesicles
  3. Secretory vesicles (electron dense granules) contain the signalling molecules adenosine diphosphate (ADP) and serotonin that activated nearby platelets
  4. Also generate thromboxane A2, a member of the eicosanoid family, from arachadonic acid
  5. Platelets change shape and stick together (aggregate) -mediated by fibrinogen receptors
37
Q

What other chemicals do platelets release when they adhere

A

thromboxane A2

38
Q

What does thromboxane do

A

(cause contraction of smooth muscle, leading to vasoconstriction- indirectly? )
promote platelet aggregation

39
Q

function of neutrophils

A
  1. Also called Polymorph(ocyte) due to the structure of the nucleus (2-5 distinct lobes)
  2. Fine granules spread evenly through cytoplasm
  3. Amoeboid movement
  4. Engulf bacteria by phagocytosis- Granules contain large amounts of enzymes required for breakdown of engulfed particles
  5. Produce inflammatory mediators-signal that there is an infection to recruit more cells
  6. Neutrophil rolls along surface of epithelial cells, enters site of infection by diapedesis, then engulfs bacteria
  7. Positive feedback causes recruit of more inflammatory cells.
40
Q

Eosinophils features

A
  1. Nucleus usually 2 occasionally 3 lobed
  2. Granules spherical & larger than in neutrophils – stain with acid dyes (reddish )
  3. Some phagocytic action
  4. Role in allergy and asthma
41
Q

Monocyte features

A
  1. Largest of blood cells
  2. Irregular- often lobed nucleus
  3. Fine granules
  4. At site of infection- can also be recruited and differentiate into new cell type- macrophage
42
Q

What are monocytes

A
  1. Phagocytes that circulate in the blood and migrate into tissues where they develop into macrophages
43
Q

What are the progenitors of platelets and how do they form

A
  1. Megakaryocytes, form when cytoplasmic portions of large bone marrow cells pinch off
44
Q

What about the structure of platelets increases its enhances plug formation

A

Contains high levels of actin/myosin and a cyoskeleton that can contract in activated platelets

45
Q

what is thrombocytopenia and why does it happen

A

bleeding disorder due to a low platelet count

Happens when the pathway leading to platelet activation is disrupted

46
Q

What are erythrocytes?

A

They are red blood cells involved in the transport of CO2 and O2. They contain haemoglobin and have a biconcave shape.

47
Q

Intrinsic pathway detailed

A
  1. XII converted into XIIa when comes into contact with collagen
  2. XIIa catalyses activation of XI into XIa,
  3. which in turn activates IX to IXa
  4. This last factor activates X to Xa, which converts prothrombin to thrombin
48
Q

Extrinsic pathway detailed

A
  1. Pathway begins with transcription factor located on outside of subendothelial cells which are exposed
  2. TF on these cells bind to factor VII, forms activated VIIa
  3. Complex formed by these then activates factor X to Xa, which converts prothrombin to thrombin
49
Q

In an uninjured blood vessel..

A

Thrombin bound to thrombomodulin (bound to the endothelial cell) activates protein C, which blocks the clotting response

50
Q

Where is the majority of blood cell production from in an adult?

A

The ribs, sternum, vetrebrae, pelvis, ribs and cranial bones.

51
Q

What else happens due to the activation and aggregation of platelets?

A

There is a discharge of mediators that result in the contraction of vascular smooth muscle to result in vasoconstriction.

52
Q

What is erythrocyte production controlled by and what is it called?

A
  1. The production is called erythropoiesis and it occurs in the bone marrow.
  2. It is controlled by a hormone called erythopoietin (EPO) which is produced by the kidney.
  3. Decreased oxygen levels trigger EPO production
    a) High altitude
    b) Lung disease
    c) Insufficient pumping of the heart
    d) Anaemia
53
Q

What happens if there is low oxygen delivery to the kidneys?

A
  1. The kidneys secrete more erythropoetin which results in more production of erythrocytes in the bone marrow. 2. There is an increase in blood Hb concentration, along with the blood carrying capacity.
54
Q

What are the 6 leukocytes?

A
  1. Basophils
  2. neutrophils
  3. eosinophils
  4. monocytes
  5. macrophages
  6. lymphocytes.
55
Q

What are the 5 types of phagocytes?

A
  1. Basophils
  2. neutrophils
  3. eosinophils
  4. monocytes
  5. macrophages.
56
Q

What are the three types of granulocytes?

A
  1. Basophils
  2. neutrophils
  3. eoisinophils.
57
Q

What are the sub divisions of lymphocytes?

A
  1. B cell - antibody production
  2. T helper cells - regulate antibody production, regulate & mediate immune reactions
  3. Natural Killer (NK) cells - lyse target cells
58
Q

What is the process for blood cell production?

A
  1. The process starts with a pluripotent stem cell
  2. This differentiates into a lymphoid or myeloid stem cell that will give rise to specific types of blood cell
  3. Myeloid stem cells differentiate into erythrocytes (red blood cells), neutrophil, monocytes, eosinophils, basophils and megakaryocytes (that fragment into tiny platelets)
  4. Lymphoid stem cells differentiate into lymphocytes
  5. These pathways are controlled by multiple growth factors and cytokines
59
Q

What is platelet aggregation?

A

When platelets change shape and stick together.

60
Q

What happens to activated platelets?

A

They release the contents of secretory vesicles that contain ADP and serotonin to activate nearby platelets.

61
Q

What is a clot

A
  1. The transformation of blood into a gel.
  2. It occurs around the platelet plug.
  3. Vessel damage activates a cascade of enzymes that result in the activation of an enzyme called Thrombin
62
Q

How is thrombin activated during clot formation?

A
  1. Prothrombinase complex forms on the surface of the activated platelet and leads to the activation of prothrombin.
  2. This is cleaved into active thrombin
  3. Thrombin is a protease enzyme that cleaves proteins 4. It that cleaves fibrinogen to form fibrin molecules that bind together to form a loose meshwork
63
Q

What is the PAR receptor?

A

A receptor found on platelets called the protease activated receptor.

64
Q

What does thrombin do to the PAR receptor?

A
  1. It binds to the N terminus of the receptor and cleaves the N terminus.
  2. The cleaved N terminus can then bind and activate the thrombin receptor
  3. So the activator (ligand) is part of the receptor itself (tethered ligand)
65
Q

How is the clotting response prevented in uninjured vessels?

A
  1. Thrombin is bound to thrombomodulin that activates protein C, which blocks the clotting response.
66
Q

How is the liver involved in the blood?

A
  1. It produces and modifies blood proteins that are used in the clotting pathway.
  2. Bile salts from the liver facilitate the absorption of lipids, including vitamin K which is required for the synthesis of prothrombin and several other clotting factors.
67
Q

What does the term tethered ligand mean?

A

The ligand of the receptor is part of the receptor itself - it activates itself.

68
Q

What are two hematopoietic growth factor

A
  1. Thrombopoietin (TPO)

2. Erythropoietin (EPO) (sometimes termed cytokines)

69
Q

What can disfunction in blood clotting lead to

A

Hemophillia

PA10315 COPY (48 decks)

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