blood Flashcards
3 steps in haemostasis
vasocontriction
platelet plug formation
clotting cascade
what happens after haemostasis
clot retraction & fibrinolysis
platelet plug- how is there growth
positive feedback system with TXA2, ADP 5-HT
platelet plug- how is the growth limited
negative feedback with anticoagulants - antagonise platelet plug
describe what happens during coagulation/clotting
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.
true or flase: Conversion of fibrinogen to fibrin is the final step in a cascade of reactions which can either follow an intrinsic pathway
false: Conversion of fibrinogen to fibrin is the final step in a cascade of reactions which can either follow an intrinsic OR extrinsic pathway.
what are most active clotting factors
serine protease enzymes
(hydrolyse peptide bonds)
what does factor XIII do
a transglutaminase (links glutamine and lysine residues)
knits the fibrin strands together
why is calcium important for blood clotting
no calcium would mean no clotting, important for the intrinsic cascade pathway
what does EDTA do
it is a calcium chelator and it takes calcium out of blood plasma and inhibit clotting in ‘in vitro’ storage
what is the cascade caused by thrimbin
Fibrinogen fibrin monomers
* Polymerisation, H bonds, fibrin strands
* Factor XIIIa covalent cross linkage stabilisation
* Stable mesh surrounds platelet plug
* Clot retraction
what surrounds the platelet plug
stable mesh
Clot Stabilisation: what is the main roles of this
circulating soluble fibrinogen to stable insoluble fibrin mesh
what is clot retraction
actin and mysoin filaments in platelets
contract, drawing edges of wound together (thrombin stimulates release of intracellular Ca++)
what is the fibrolytic system also known as
thrombolytic system
fibrolytic system: role of this system
clot dissolution breakdown
Fibrolytic systems: what is the fibrin clots catalysed by
Catalysed by the enzyme plasmin. Digests fibrin present in clots
Fibrolytic System: where is plasmin from
converted from plasminogen, which circulates in an inactive form
Fibrolytic System: which molecules ciruclate in their inactive forms
fibrinogen, plasminogen
Fibrolytic System: what is t-PA inhibited by
Inhibited by Plasmin Activator Inhibitor (PAI-1) – platelets rich source
Fibrolytic System: how to increase activity of t-PA
Binding to fibrin increases the enzymatic activity of t-PA
Fibrolytic System: what does t-PA stand for
Tissue plasminogen activator
Fibrolytic System: where is t-PA release
released by endothelial cells, incorporated in clot during formation
Fibrolytic System: where is t-PA ‘s function
promotes conversion of plasminogen to plasmin leading to breakdown of fibrin, fibrinogen and Factors V and VIII
name 5 anti coagulation agents
prostacyclin, nitric oxide, heparin, thrombomodulin, tissue factor pathway inhibitor (TFPI)
what are the commonly used drugs affecting haemostasis
aspirin, warfarin
role of aspirin and warfarin
Both reduce clotting ability and therefore potentially lead to increased bleeding time
role of Prostacyclin
vasodilator, antagonises TXA2
role of Heparin
binds to and activates circulating plasma protein antithrombin. Neutralises clotting factors (IX-XII)
role of Nitric oxide (NO)
vasodilator, opposes platelet aggregation
role of Tissue Factor Pathway Inhibitor (TFPI)
binds to and inhibits thromboplastin/Factor VII complex
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)
what does warfarin do
inhibits the action of vitamin K reductase, hence less conversion of
Vitamin K-2,3 epoxide to VITK-H2
true or false: warfarin takes into action quickly
false: takes long time to take effect
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
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
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)
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)
name the 6 functions of blood
- Carriage of physiologically active compounds (plasma)
- Clotting (platelets)
- Defence (white blood cells)
- Carriage of gas (red blood cells)
- Thermoregulation
- Maintenance of ECF pH
CCCDTM
what is the composition of blood
Consists of plasma, red blood cells, white blood cells and platelets
what is the composition of plasma
4% body weight and 95% water, Composition normally kept within strict limits.
what is Colloid Oncotic Pressure
is a form of osmotic pressure induced by proteins, notably albumin, in a blood vessel’s plasma
true or false: plasma proteins can readily cross the capillary wall
false: Plasma proteins do not readily cross the capillary wall
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
what does the vessel lumen vs Interstitial space
contain
plasma proteins and blood plasma
Interstitial space: Interstitial fluid - Na+, H2O and glucose
what does the Interstitial fluid act as
Interstitial fluid acts as fluid reservoir (volume approx. 3-4 times greater than plasma)
what are the 3 plasma proteins
albumin, globulin (subdivided into a, ß, y globulins), fibrinogens and other clotting factors
function of plasma
circulates biological active molecules and compounds
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
describe the difference between first and exposure time to pathogens in the adaptive immune response
The second exposure begins earlier than the 1st exposure
describe the difference between first and exposure time to pathogens in the innate immune response
the time is the same in both exposures
what is the first vs second line of defence in body
physical barrier is 1st
immune system is 2nd
describe the 2nd line of defence: the 2 types ?
- Innate immune system
- Adaptive immune system
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)
Cells of the immune system: where do they come from?
self renewing stem cells differentiate into –> bi-potential cells –> myeloid cells and lymphoid cells
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
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
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
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)
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
how are cytokines produced
Produced by many different cell types in response to microbes, tissue damage or other antigens
Innate Immunity: Phagocytic cells types
Neutrophils
Macrophages
Innate Immunity: Neutrophils production site
bone marrow
Innate Immunity: are Neutrophils fast or slow in response to infection
First to arrive to site of infection
Innate Immunity: Neutrophils lifespan
5 days
what is the most common WBCs and what are they also known as
Neutrophils, also known as Pus
what is Pus made of
dead neutrophils and bacteria.
Innate Immunity: Neutrophils – name 3 killing mechanisms
Phagocytosis:
Degranulation:
NETosis:
what is phagocytosis
process of engulfing and killing pathogens (They can ingest between 10 and 20
bacteria at a time!)
what is degranulation
Release of the content of the granules to the environment to kill microbes (but can also damage host tissues!)
what is NETosis
the process of generation of Neutrophil Extracellular Traps (NETs) formed by DNA and histones, granular proteins, and cytoplasmic proteins
Innate Immunity: what does macrophages mean
big eaters
Innate Immunity: macrophages function
Functions: clearance of microbes but also
apoptotic cells and foreign particles
Innate Immunity: Mast cells and Basophils function once activated
Degranulation: Release of store preformed mediators (e.g. histamine, proteases, cytokines)
Innate Immunity: how are Mast cells and Basophils stored
M: Sentinels in tissues
B: circulate in blood
Innate Immunity: Mast cells and Basophils mainly respond to
allergic reactions
Innate Immunity: Mast cells and Basophils, what do they both contain within them
both contains many large cytoplasmic granules containing preformed mediators
Innate Immunity: where are macrophages precursors formed and where are macrophages founded
Precursors formed in bone marrow
Macrophages are found in tissues
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
Innate Immunity: Eosinophils function
- Help combat parasitic infections – helminths with Granules contain many toxic enzymes
- Involved in allergy and asthma as well
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.
Innate Immunity: Natural Killer (NK) cells (I) half life and percentage within lymphocytes
10-15% lymphocytes.
* Half-life of about a week
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
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.
Innate Immunity: soluble factors (I) - describe the complement system
Three pathways - activated by microbes (lectin
and alternative) or antibodies (classical).
Innate Immunity: soluble factors (I) - where does the complement system activation
Activation of the complement happens on the
surface of target cells.
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.
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
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)
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.
what are the soluble factors of adaptive immunity
antibodies
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
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
Adaptive Immunity: name the 2 types of Effector T lymphocytes (T cells)
Helper T cells (Th cells) and Cytotoxic T cells (CTL)
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
function of Cytotoxic T cells
kill infected cells or tumour cells
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.
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.
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)
true or false: antibodies can kill pathogens
false- do not kill pathogens, they identify and
neutralise and/or tag
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
What happens when the immune system does not
work properly? (I)
Severe infection, septic shock or anaphylactic shock
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
what happens within anaphylactic shock
successive exposure to allergens allows for mediators release within MAST CELLS
Hypoproteinaemia causes
prolonged starvation
liver disease
intestinal diseases
nephrosis (kidney disease)
what is Hypoproteinaemia
Abnormally low levels of circulating plasma protein
Hypoproteinaemia common characteristics
oedema (swelling) due to loss of oncotic pressure
provide examples for RBC and WBC
RBC: Erythrocytes
WBC Neutrophil, Monocyte, Basophil, Eosinophil, Lymphocyte
are platelets WBCs ?
no they are myeloid cells
name all the myeloid cells
Erythrocytes, Neutrophil, Monocyte, Basophil, Eosinophil, Platelets
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
what does erythrocytes contain
Densely packed with Haemoglobin – protein concerned with gas transport.
why does a colour change within the erythrocytes happen
Colour change
– oxyhaemoglobin (arterial)
- deoxyhaemoglobin (venous)
Erythropoiesis (Red Blood Cell Formation): what is erythropoietin
Controls and accelerates Erythropoiesis, stimulating pluripotent stem cells –> erythroblast
Erythropoiesis (Red Blood Cell Formation):where is the erythropoietin secreted from
Secretion - 85% kidney, 15% liver
Erythropoiesis (Red Blood Cell Formation):what does a 2-3 delay mean
2-3 day delay = Renal disease
Erythropoiesis (Red Blood Cell Formation):how is secretion enhanced
when oxygen delivery to kidneys is reduced, also known as hypoxia
Erythropoiesis (Red Blood Cell Formation):what is hypoxia and how is it induced
less O2 delivered to kidney
haemorrhage/anaemia/cardiac dysfunction/ lung disease
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
WBC family tree: name the 2 types of WBCs
Granulocytes and Agranulocytes
WBC family tree: name the 2 types of Agranulocytes
Monocytes and Lymphocytes
WBC family tree: name the 2 types of Granulocytes
Neutrophils, Basophils, Eosinophils
WBC family tree: name the 2 types of Lymphocytes
B cells and T cells (Helper and Killer )
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.
WBC family tree: describe Neutrophils (abundance, half life, produce 100bn/day)
Most abundant 68%
Half life ~10hrs
Produce 100bn/day
WBC family tree: percentage of circulating cells of lymphocytes and basophils
L: 25%
B: <1%, least abundant
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
Leukopoiesis (white blood cell formation): name examples of cytokines within the cytokines cocktail
Colony Stimulating Factors e.g. Granulocyte CSF,
Interleukins
Leukopoiesis (white blood cell formation): describe the process
Cytokines are released from mature white blood cells.
Stimulate both mitosis and maturation of leukocyte
Leukopoiesis (white blood cell formation): what are the 2 types of differential stimulation in response to infection
bacterial - increase neutrophils
Viral - increases lymphocytes
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.
Leukopoiesis (white blood cell formation): what does Differential White Cell Count allow for
Differential White Cell Count allows you to differentiate between infection types.
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)
Platelets: what is its formation controlled by
Formation governed by Thrombopoietin
Platelet function
Adhere to damaged vessel walls and exposed connective tissue to mediate
blood clotting
DO NOT adhere to healthy intact endothelium
What is a Haematocrit
refers to the percentage of the total blood volume that is composed of red blood cells (RBCs).
what is the normal percentage range for Haematocrit
40-50%
what is centrifugation used for
separate whole blood into Plasma, WBCs + Platelets, RBCs (this order is the same density order after centrifugation)
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
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.
