blood Flashcards

(141 cards)

1
Q

3 steps in haemostasis

A

vasocontriction
platelet plug formation
clotting cascade

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2
Q

what happens after haemostasis

A

clot retraction & fibrinolysis

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3
Q

platelet plug- how is there growth

A

positive feedback system with TXA2, ADP 5-HT

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4
Q

platelet plug- how is the growth limited

A

negative feedback with anticoagulants - antagonise platelet plug

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5
Q

describe what happens during coagulation/clotting

A

After the platelets have aggregated and bound to Von Willibrand Factor, the next step in reducing blood loss is to convert the blood around the site of damage into a plug with a solid gel like consistency
Circulating soluble plasma proteins called fibrinogen
are converted to insoluble polymer strands of fibrin
which form a mesh, trapping blood cells and preventing blood loss.

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6
Q

true or flase: Conversion of fibrinogen to fibrin is the final step in a cascade of reactions which can either follow an intrinsic pathway

A

false: Conversion of fibrinogen to fibrin is the final step in a cascade of reactions which can either follow an intrinsic OR extrinsic pathway.

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7
Q

what are most active clotting factors

A

serine protease enzymes
(hydrolyse peptide bonds)

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8
Q

what does factor XIII do

A

a transglutaminase (links glutamine and lysine residues)
knits the fibrin strands together

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9
Q

why is calcium important for blood clotting

A

no calcium would mean no clotting, important for the intrinsic cascade pathway

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10
Q

what does EDTA do

A

it is a calcium chelator and it takes calcium out of blood plasma and inhibit clotting in ‘in vitro’ storage

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11
Q

what is the cascade caused by thrimbin

A

Fibrinogen fibrin monomers
* Polymerisation, H bonds, fibrin strands
* Factor XIIIa covalent cross linkage stabilisation
* Stable mesh surrounds platelet plug
* Clot retraction

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12
Q

what surrounds the platelet plug

A

stable mesh

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13
Q

Clot Stabilisation: what is the main roles of this

A

circulating soluble fibrinogen to stable insoluble fibrin mesh

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14
Q

what is clot retraction

A

actin and mysoin filaments in platelets
contract, drawing edges of wound together (thrombin stimulates release of intracellular Ca++)

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15
Q

what is the fibrolytic system also known as

A

thrombolytic system

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16
Q

fibrolytic system: role of this system

A

clot dissolution breakdown

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17
Q

Fibrolytic systems: what is the fibrin clots catalysed by

A

Catalysed by the enzyme plasmin. Digests fibrin present in clots

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18
Q

Fibrolytic System: where is plasmin from

A

converted from plasminogen, which circulates in an inactive form

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19
Q

Fibrolytic System: which molecules ciruclate in their inactive forms

A

fibrinogen, plasminogen

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20
Q

Fibrolytic System: what is t-PA inhibited by

A

Inhibited by Plasmin Activator Inhibitor (PAI-1) – platelets rich source

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21
Q

Fibrolytic System: how to increase activity of t-PA

A

Binding to fibrin increases the enzymatic activity of t-PA

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22
Q

Fibrolytic System: what does t-PA stand for

A

Tissue plasminogen activator

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23
Q

Fibrolytic System: where is t-PA release

A

released by endothelial cells, incorporated in clot during formation

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24
Q

Fibrolytic System: where is t-PA ‘s function

A

promotes conversion of plasminogen to plasmin leading to breakdown of fibrin, fibrinogen and Factors V and VIII

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25
name 5 anti coagulation agents
prostacyclin, nitric oxide, heparin, thrombomodulin, tissue factor pathway inhibitor (TFPI)
26
what are the commonly used drugs affecting haemostasis
aspirin, warfarin
27
role of aspirin and warfarin
Both reduce clotting ability and therefore potentially lead to increased bleeding time
28
role of Prostacyclin
vasodilator, antagonises TXA2
29
role of Heparin
binds to and activates circulating plasma protein antithrombin. Neutralises clotting factors (IX-XII)
30
role of Nitric oxide (NO)
vasodilator, opposes platelet aggregation
31
role of Tissue Factor Pathway Inhibitor (TFPI)
binds to and inhibits thromboplastin/Factor VII complex
32
role of thrombomodulin
binds thrombin to inhibit clotting. Protein C + co-factor, protein S, inactivate clotting factors V and VIII and promotes formation of plasmin from plasminogen (degrades clot)
33
what does warfarin do
inhibits the action of vitamin K reductase, hence less conversion of Vitamin K-2,3 epoxide to VITK-H2
34
true or false: warfarin takes into action quickly
false: takes long time to take effect
35
describe the fibrolytic system cascade
Dietary Vit.K --> Gamma-glutamyl carboxylase activates clotting factors II, VII, IX, X, vitamin --> Vit.K reductase reduces from K-2,3 epoxide to Vitamin K-H2
36
describe the difference between activations of the intrinsic and extrinsic pathway
intrinsic: activated by collagen and other activators and positive feedback of thrombin extrinsic pathway: activated through exposure of tissue factor III and positive feedback of active X
37
describe the common pathway of the intrinsic and extrinsic pathway
prothrombin - fibrinogen - fibrin- active XIII- cross linked fibrin positive feedback of thrombin (IP) and active x (EP)
38
how much blood is there in a healthy 70 kg man, in a woman and new-born baby
Man: 5 litres of blood: 1L in lungs, 3L in systemic venous circulation, 1L in heart and arterial circulation New born baby: 350ml Less in women (approx. 7-8% body weight)
39
name the 6 functions of blood
1. Carriage of physiologically active compounds (plasma) 2. Clotting (platelets) 3. Defence (white blood cells) 4. Carriage of gas (red blood cells) 5. Thermoregulation 6. Maintenance of ECF pH CCCDTM
40
what is the composition of blood
Consists of plasma, red blood cells, white blood cells and platelets
41
what is the composition of plasma
4% body weight and 95% water, Composition normally kept within strict limits.
42
what is Colloid Oncotic Pressure
is a form of osmotic pressure induced by proteins, notably albumin, in a blood vessel's plasma
43
true or false: plasma proteins can readily cross the capillary wall
false: Plasma proteins do not readily cross the capillary wall
44
how is net movement determined from interstitial space through capillary wall to vessel lumen with blood plasma/ plasma proteins
Net direction of movement is determined by balance between colloid oncotic pressure (favours movement into capillary) and capillary hydrostatic pressure (blood pressure) which favours movement out of capillary
45
what does the vessel lumen vs Interstitial space contain
plasma proteins and blood plasma Interstitial space: Interstitial fluid - Na+, H2O and glucose
46
what does the Interstitial fluid act as
Interstitial fluid acts as fluid reservoir (volume approx. 3-4 times greater than plasma)
47
what are the 3 plasma proteins
albumin, globulin (subdivided into a, ß, y globulins), fibrinogens and other clotting factors
48
function of plasma
circulates biological active molecules and compounds
49
innate vs adaptive immune system difference
INNATE First to come into play – quick response * Non-specific response *no ‘memory’ ADAPTIVE * Slower response * Highly specific response * Immunological memory
50
51
describe the difference between first and exposure time to pathogens in the adaptive immune response
The second exposure begins earlier than the 1st exposure
52
describe the difference between first and exposure time to pathogens in the innate immune response
the time is the same in both exposures
53
what is the first vs second line of defence in body
physical barrier is 1st immune system is 2nd
54
describe the 2nd line of defence: the 2 types ?
* Innate immune system * Adaptive immune system
55
describe the 1st line of defence
PHYSICAL BARRIERS * Skin * Respiratory tract (e.g. mucus, cilia) * Digestive tract (e.g. stomach pH, intestinal antimicrobial peptides) * Reproductive tract (e.g. antimicrobial peptides)
56
Cells of the immune system: where do they come from?
self renewing stem cells differentiate into --> bi-potential cells --> myeloid cells and lymphoid cells
57
Cells of the immune system: examples of the myeloid cells and which type of immune system to they belong to
Basophil, Mast cell, Eosinophil, Neutrophil, Dendritic cell, Monocyte, RBC, NK cell Innate immune cells
58
examples of the Cells of the immune system: lymphoid cells and which type of immune system to they belong to
T cell, B cell Adaptive immune cells
59
what does PAMPs stand for and what is its function
Pathogen Associated Molecular Patterns Cells of innate immune system recognize molecular patterns that are conserved in microbes Examples: lipopolysaccharide, flagellin
60
what does PRRs stand for, what is its function and provide an example
Pattern-Recognition Receptors Immune cells recognize PAMPs using Pattern-Recognition Receptors (PRRs) Example: Toll-like receptors (TLRs)
61
cytokines functions
soluble mediators the communication system that acts locally or at a distance Regulate and co-ordinate the cells of innate and adaptive immunity ie drive immune responses Powerful – need to be well-controlled
62
how are cytokines produced
Produced by many different cell types in response to microbes, tissue damage or other antigens
63
Innate Immunity: Phagocytic cells types
Neutrophils Macrophages
64
Innate Immunity: Neutrophils production site
bone marrow
65
Innate Immunity: are Neutrophils fast or slow in response to infection
First to arrive to site of infection
66
Innate Immunity: Neutrophils lifespan
5 days
67
what is the most common WBCs and what are they also known as
Neutrophils, also known as Pus
68
what is Pus made of
dead neutrophils and bacteria.
69
Innate Immunity: Neutrophils – name 3 killing mechanisms
Phagocytosis: Degranulation: NETosis:
70
what is phagocytosis
process of engulfing and killing pathogens (They can ingest between 10 and 20 bacteria at a time!)
71
what is degranulation
Release of the content of the granules to the environment to kill microbes (but can also damage host tissues!)
72
what is NETosis
the process of generation of Neutrophil Extracellular Traps (NETs) formed by DNA and histones, granular proteins, and cytoplasmic proteins
73
Innate Immunity: what does macrophages mean
big eaters
74
Innate Immunity: macrophages function
Functions: clearance of microbes but also apoptotic cells and foreign particles
75
Innate Immunity: Mast cells and Basophils function once activated
Degranulation: Release of store preformed mediators (e.g. histamine, proteases, cytokines)
76
Innate Immunity: how are Mast cells and Basophils stored
M: Sentinels in tissues B: circulate in blood
77
Innate Immunity: Mast cells and Basophils mainly respond to
allergic reactions
78
Innate Immunity: Mast cells and Basophils, what do they both contain within them
both contains many large cytoplasmic granules containing preformed mediators
79
Innate Immunity: where are macrophages precursors formed and where are macrophages founded
Precursors formed in bone marrow Macrophages are found in tissues
80
Innate Immunity: what macrophages travel as
Circulate as monocytes (they remain in the blood around 3 days) and migrate towards tissues where they become macrophages
81
Innate Immunity: Eosinophils function
* Help combat parasitic infections – helminths with Granules contain many toxic enzymes * Involved in allergy and asthma as well
82
Innate Immunity: Natural Killer (NK) cells (I) function
Cells containing granules which contain enzymes – apoptosis of target cell. * Cells that kill a variety of tumour/virus infected cells.
83
Innate Immunity: Natural Killer (NK) cells (I) half life and percentage within lymphocytes
10-15% lymphocytes. * Half-life of about a week
84
Innate Immunity: how do Natural Killer (NK) cells (II) kill or prevent killing
Activating receptor bind to target cell Inhibitory receptor binds to MHC I
85
Innate Immunity: soluble factors (I) - The complement system function
Enzyme cascade system comprising several factors found in the plasma in an inactive form - main components C1 to C9.
86
Innate Immunity: soluble factors (I) - describe the complement system
Three pathways - activated by microbes (lectin and alternative) or antibodies (classical).
87
Innate Immunity: soluble factors (I) - where does the complement system activation
Activation of the complement happens on the surface of target cells.
88
Innate Immunity: soluble factors (I) - what does the complement system
Activation of the complement leads to the cleavage of complement components into large and small active fragments – they have different functions within the immune response.
89
Innate Immunity: soluble factors (I) - what does theC3a and C5a do within the complement system
C3a and C5a (the small fragments) activate immune cells and serve as chemoattractant – activate further the immune response
90
Innate Immunity: soluble factors (I) - what does the C3b do within the complement system
Molecules such as C3b can act as tags which enhance phagocytosis (= opsonins)
91
Innate Immunity: soluble factors (I) - what does the C5b do within the complement system
C5b can combine with other complement proteins (C6, C7, C8, C9) to make the membrane attack complex (MAC) – forms pores on the membrane of pathogens.
92
what are the soluble factors of adaptive immunity
antibodies
93
Innate Immunity: Dendritic cells unction
act as Antigen-presenting cell (APC) * Recognizes and internalizes pathogen and processes it into peptides which it presents (antigen) activating T cells of adaptive immune system
94
Adaptive Immunity: T lymphocytes (T cells) function
T cells respond to antigen only when presented by an antigen-presenting cell (APC) allowing for antigen T cells differentiate to effector T cells * Dendritic cells (DC) and macrophages can be APC
95
Adaptive Immunity: name the 2 types of Effector T lymphocytes (T cells)
Helper T cells (Th cells) and Cytotoxic T cells (CTL)
96
function of Helper T cells
Alter immune responses by secreting cytokines * Help other cells: e.g. help B cells to make antibody, activate macrophages, recruit other immune cells … * Different subsets (Th1, Th2, Th17, Tfh) make different cytokines – fine tune the immune response
97
function of Cytotoxic T cells
kill infected cells or tumour cells
98
Adaptive Immunity: B lymphocytes (B cells) function
Cells that produce antibodies. * B cells recognize a small part of an antigen called epitope using the B cell receptor (a membrane-bound antibody) * This interaction with the epitope activates the B cell which then starts a maturation process. * At the end of their maturation, some B cells will then become plasma cells (antibody factories) while others will become a memory B cell.
99
Adaptive Immunity: how does B lymphocytes (B cells) produce antibodies function, describe process
* B cells recognize a small part of an antigen called epitope using the B cell receptor (a membrane-bound antibody) * This interaction with the epitope activates the B cell which then starts a maturation process. * At the end of their maturation, some B cells will then become plasma cells (antibody factories) while others will become a memory B cell.
100
describe the sections of the antibodies
Y” shape made up of 2 heavy (long) chains and 2 light (short) chains. * Every antibody has 2 antigen binding sites that bind the same antigen * Antibodies bind the antigen through one region (Fab) and interact with other immune cells and the complement through another portion (Fc)
101
true or false: antibodies can kill pathogens
false- do not kill pathogens, they identify and neutralise and/or tag
102
name the 5 different classes of antibody
GAMED * IgG – Good opsonizer, maternal antibody * IgA – Protects mucosal surfaces, resistant to stomach acid IgM –Good at activating complement and opsonization * IgE – Defends against parasites, causes anaphylactic shock and allergies * IgD – Enigmatic antibody
103
What happens when the immune system does not work properly? (I)
Severe infection, septic shock or anaphylactic shock
104
what happens during Severe infection and septic shock
Severe infection with microbes in blood * Innate immune cells respond and produce cytokines and other immune mediators * Cytokine storm * Can be fatal without rapid treatment
105
what happens within anaphylactic shock
successive exposure to allergens allows for mediators release within MAST CELLS
106
Hypoproteinaemia causes
prolonged starvation liver disease intestinal diseases nephrosis (kidney disease)
107
what is Hypoproteinaemia
Abnormally low levels of circulating plasma protein
108
Hypoproteinaemia common characteristics
oedema (swelling) due to loss of oncotic pressure
109
provide examples for RBC and WBC
RBC: Erythrocytes WBC Neutrophil, Monocyte, Basophil, Eosinophil, Lymphocyte
110
are platelets WBCs ?
no they are myeloid cells
111
name all the myeloid cells
Erythrocytes, Neutrophil, Monocyte, Basophil, Eosinophil, Platelets
112
describe the Erythrocytes (e.g. lifespan, composition, diameter )
red blood cells Most abundant blood cell (4 - 6 x10^12/L) 120 day lifespan. Highly flexible, biconcave, non-nucleated, diameter 7-8um
113
what does erythrocytes contain
Densely packed with Haemoglobin – protein concerned with gas transport.
114
why does a colour change within the erythrocytes happen
Colour change – oxyhaemoglobin (arterial) - deoxyhaemoglobin (venous)
115
Erythropoiesis (Red Blood Cell Formation): what is erythropoietin
Controls and accelerates Erythropoiesis, stimulating pluripotent stem cells --> erythroblast
116
Erythropoiesis (Red Blood Cell Formation):where is the erythropoietin secreted from
Secretion - 85% kidney, 15% liver
117
Erythropoiesis (Red Blood Cell Formation):what does a 2-3 delay mean
2-3 day delay = Renal disease
118
Erythropoiesis (Red Blood Cell Formation):how is secretion enhanced
when oxygen delivery to kidneys is reduced, also known as hypoxia
119
Erythropoiesis (Red Blood Cell Formation):what is hypoxia and how is it induced
less O2 delivered to kidney haemorrhage/anaemia/cardiac dysfunction/ lung disease
120
describe Leukocytes (how much per litre, involved in ...)
white blood cells nucleated, larger than RBC’s, In total: approx. 1 x 1010 per litre Involved in defence against pathogen
121
WBC family tree: name the 2 types of WBCs
Granulocytes and Agranulocytes
122
WBC family tree: name the 2 types of Agranulocytes
Monocytes and Lymphocytes
123
WBC family tree: name the 2 types of Granulocytes
Neutrophils, Basophils, Eosinophils
124
WBC family tree: name the 2 types of Lymphocytes
B cells and T cells (Helper and Killer )
125
WBC family tree: Monocyte life cycle and percentage of circulating cells
5% circulating cells, after 72 hours migrate to connective tissue where they become macrophages and live for 3 months.
126
WBC family tree: describe Neutrophils (abundance, half life, produce 100bn/day)
Most abundant 68% Half life ~10hrs Produce 100bn/day
127
WBC family tree: percentage of circulating cells of lymphocytes and basophils
L: 25% B: <1%, least abundant
128
Leukopoiesis (white blood cell formation): what is it controlled by
Controlled by a cocktail of cytokines proteins/peptides released from one cell type which act on another). Colony Stimulating Factors
129
Leukopoiesis (white blood cell formation): name examples of cytokines within the cytokines cocktail
Colony Stimulating Factors e.g. Granulocyte CSF, Interleukins
130
Leukopoiesis (white blood cell formation): describe the process
Cytokines are released from mature white blood cells. Stimulate both mitosis and maturation of leukocyte
131
Leukopoiesis (white blood cell formation): what are the 2 types of differential stimulation in response to infection
bacterial - increase neutrophils Viral - increases lymphocytes
132
Leukopoiesis (white blood cell formation): what does differential stimulation in response to infection suggest about the cytokine cocktail
the cytokine cocktail is therefore dynamic, changing it’s composition in response to infection to influence which white blood cell will be preferentially stimulated to form.
133
Leukopoiesis (white blood cell formation): what does Differential White Cell Count allow for
Differential White Cell Count allows you to differentiate between infection types.
134
describe the Erythrocytes (e.g. lifespan, composition, diameter )
membrane bound cell fragments (from megakaryocytes). Rarely nucleated, 2-4m diameter. Life span 10 days. (140-400x10^9/L)
135
Platelets: what is its formation controlled by
Formation governed by Thrombopoietin
136
Platelet function
Adhere to damaged vessel walls and exposed connective tissue to mediate blood clotting DO NOT adhere to healthy intact endothelium
137
What is a Haematocrit
refers to the percentage of the total blood volume that is composed of red blood cells (RBCs).
138
what is the normal percentage range for Haematocrit
40-50%
139
what is centrifugation used for
separate whole blood into Plasma, WBCs + Platelets, RBCs (this order is the same density order after centrifugation)
140
what is the viscosity of plasma compared to whole blood
plasma - 1.8 x thicker than water Whole blood - x 3-4 thicker than water
141
is viscosity an absolute value or not and why
no, Viscosity is not an absolute value as it depends on: haematocrit - 50% increase in haematocrit (increases viscosity approx. 100%) temperature - increase in temp decreases viscosity and vice versa(1oC changes viscosity by around 2%) flow rate - decreased flow rate increases viscosity and vice versa.