Cardiovascular Flashcards
how much of the blood is fluid and how much is plasma?
45% cellular 55% fluid
what is the lifespan of erythrocytes?
120 days but usually regenerated every 30 days
what is the lifespan of platelets?
7-10 days
3 important haemopoietic growth factors
- Erythropoietin (EPO)
- red cells
- Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)
- white cells
- Thrombopoietin
- platelets
Male and Female normal erythrocyte count
- Female
- ~4 x 1012 / L
- Male
- ~5 x 1012 / L
Haemoglobin structure
- a tetramer of two alpha chains and two beta chains
- each has a central porphyrin ring with an Fe2+
five types of anaemia
what is haematocrit
the ratio of the volume of red blood cells to the total volume of blood
often presented as a percentage
what is mean corpuscular haemoglobin
a measure of the average mass of haemoglobin per red cell
what is corpuscular volume
the measure of the average volume of a red blood cell
Acute anaemia
due to blood loss
low haemoglobin but haematocrit remains at 45%
Chronic anaemia
due to inflammatory disorders or malignancy
reduced Hb and reduced haematocrit (~20%)
iron deficiency anaemia
- poor diet, malabsorbtion, chronic bleeding
- low mean corpuscular volume
- low mean corpuscular haemoglobin
- hematocrit remains at 45%
Megaloblastic anaemia
- Macrocytosis
- abnormally large RBCs (high MCV)
- reduced production of normal RBCs leads to low Hb
- this can be caused by liver disease, alcohol abuse and hypothyroidism
B12 and Folate
- These are required for DNA synthesis
- they affect all dividing cells but blood cells first
- bone marrow is the most active source of dividing cells
- B12 absorbtion requires intrinsic factor from gastric parietal cells
- pernicious anaemia is AA disorder where these are destroyed
Haemolytic anaemia
- red blood cell lifespan reduced to <30 days (120 is normal)
- increased RBC production
- increases haem turnover leading to jaundice and anaemia
- can be inherited or congential
Neutrophil lifespan
6-10 hours
Monocyte lifespan
20-40 weeks
Lymphocyte lifespan
weeks to years
Basophil and eosinophil lifespan
days
what is the most numerous white blood cell in the blood
neutrophils
how many lymphocytes are T cells and how many are B cells?
- 20% of lymphocytes are B cells
- 80% of lymphocytes are T cells
summarise what all the different types of white blood cells do
monocytes also turn into macrophages (phagocytosis) and dendritic cells (APC)
what kind of proteins are soluble in plasma?
albumin
immunoglobulins
clotting proteins
carrier proteins
Haemophilia A is the deficiency of which clotting factor
VIII
remember 8 sounds like A
treated with recombinant factor VIII
Haemophilia B
Deficiency of factor IX
treat with recombinant factor IX
what is haemostasis and what are the three overall steps?
the arrest of bleeding
three steps:
- vasoconstriction (endothelin 1 and neural control)
- formation of platelet plug
- coagulation - platelet plug reinforced with a fibrin mesh
what happens following damage to a blood vessel
- blood vessel constricts due to neural control and endothelin-1
- two endothelial surfaces of the vessell stick together
- permanent closure due to constriction and contact stickiness only occurs in microvasculature
- in order to arrest bleeding there must first be the formation of a platelet plug and then the coagulation cascade
Platelet plug formation
- disrupted endothelium exposes collagen fibres
- platelets adhere to these via von willebrand factor
- platelet binding causes them to activate and degranulate
- activation = formation of spines so greater surface area and up-regulation of glycoprotein receptors on their surface
- these glycoprotein receptors bind fibrinogen
- old platelets bind new ones and they all aggregate
- they are sort of cross linked by fibrinogen
- platelets contain actin and myosin - this allows contraction and strengthening of the plug
what stops the platelet plug expanding into normal endothelium
- healthy endothelium secretes prostaglandin which is a vasodilator and inhibits platelet aggragation
- healthy endothelium also secretes NO2 which is a vasodilator and an inhibitor of adhesion, activation and aggregation
what is the difference between the intrinsic and the extrinsic pathway of coagulation
- Extrinsic - a cellular component from outside the blood is needed
- Intrinsic - all factors required are found in the blood
- the extrinsic pathway is the most common initiator
- thrombin links the two pathways
Intrinsic pathway of coagulation
Roman numerals should be used
- factor 12 is activated to factor 12a when it is exposed to collagen
- factor 12a catalyses the activation of factor 11 into 11a
- factor 11a catalyses the activation of factor 9 into factor 9a
- factor 9a catalyses the activation of factor 10 into factor 10a
- here factor 8a is used as a cofactor
- factor 10a is the factor that converts prothrombin to thrombin
- thrombin converts soluble fibrinogen to insoluble fibrin fibres ]
Extrinsic pathway of coagulation
- begins with tissue factor which is not a plasma protein but a protein that is located on the outer plasma membrane of various cells outside the endothelium
- tissue factor binds factor 7 which is activated to factor 7a
- complex of tissue factor and factor 7a then catalyses the activation of:
- factor 10 into factor 10a
- factor 9 into factor 9a
- factor 9a activates more factor 10
- factor 10a activates prothrombin into thrombin
give an example of a cell that expresses tissue factor
fibroblasts
thrombin feedback
- activates factors 11 and 8 of the intrinsic pathway (positive feedback)
- thrombin activates platelets
- the amount of thrombin generated using only the extrinsic pathway is not enough to clot properly
- possitive feedback is essential for a clot to form
two reasons liver damage causes poor clotting
- the clotting factors ( including prothrombin) are produced in the liver
- the liver produces bile salts which are essential for the absorbtion of fat soluble vitamins
- vitamin K is a fat soluble vitamin
- Vitamin K is needed for post translational modification of clotting factors 2, 7, 9 and 10. (1972)
- NB factor 2 is prothrombin
draw and annotate a sarcomere
what is the I band
Only thin filaments
what are the z lines
these cross only thin filaments and they define the boundary of one sarcomere
what is the H zone
this is the area on the sarcomere with only thick filaments
this reduces with contraction
what is the m line?
this is the centre of the H zone - down the middle of the sarcomere
Thin filaments
- actin is globular and monomers plymerise to form two intertwined helical chains
- each actin molecule has a binding site for myosin
- tropomyosin lies in the groove between the two actin filaments, covering the myosin binding site
- troponin is a protein on the tropomyosin
- it can change shape when it binds to Ca2+ and this moves the tropomyosin, exposing the myosin binding sites
Thick filaments
- myosin
- two large chains and four smaller chains
- combine forming a molecule with two globular heads
- globular heads form cross bridges with the neighbouring actin filament
- each globular head has two binding sites
- one for the thin filament and one for binding ATP
- the ATP binding site is an ATPase that hydrolyses ATP and uses this energy for contraction
what is titin
Titin connexts the Z line to the M line
it is an elastic protein
it maintains the alignment of the sarcomere
what is the sarcoplasmic reticulum
- this is a membrane network that surrounds the contractile proteins
- it is the cell’s internal calcium store and can supply the calcium needed for contraction
- releases calcium when ca2+ binds to its ryanodine receptor
describe the ion distribution inside and outside of a cardiomyocyte at rest
- the inside of the cell is more negative than the outside (-90mV)
- there’s more Ca2+ and Na+ outside of the cell
- there’s more K+ inside of the cell
- ATPase pumps 3Na+ ions out of the cell for every 2K+ ions pumped in
- this maintains the membrane potential
- Ca2+ moves across the membrane through calcium channels
Types of calcium channels in the heart
L-type channels and T-type channels
what are t tubules
- these run from the cell’s surface to deep within the cell
- they are continuous with the membrane
- in the centre of the cell they form a network
- they associate with the terminal cisternae
what is the pacemaker of the heart
the SA node
The pacemaker cells are modified cardiomyocytes that have lost the ability to contract
what speed do electrical impulses travel through the heart?
1m/s
Pacemaker action potential
- there is no true resting potential in these cells
- K+ travels out of the cell leading to hyperpolarisation (-60mV)
- this triggers the hyperpolarisation activated cyclic nucleotide-gated (HCN) channels
- Na+ slowly enters the cell through these channels causing diastolic depolarisation to (-40mV)
- at -40mV Ca2+ ion channels open
- rapid calcium influx depolarises to +20mV
- this is the action potential
- the action potential spreads from one cell to the other via gap junctions in intercalated discs
- K+ then effluxes from the cell causing repolarisation
HCN channels
- unique to the heart
- they are opened by catecholamines like noradrenaline
- if more are open there’s faster transfer of Na+ into the cell
- there’s faster reaching of -40mV threshold
- there’s faster heartrate
- they are closed by Ach
- if fewer are open then there’s slower transfer of Na+ into the cell
- slower reaching of -40mV threshold
- and the heartrate slows
myocardiocyte action potential
Excitation contraction coupliung
- Influx of calcium from the ECF (during the plateau) is not enough to induce contraction - Ca2+ from the sarcoplasmic reticulum is needed
- T tubules contain more calcium channels than the rest of the membrane
- Ca2+ enters the cell at the t tubule and binds the ryanodine receptor on the sarcoplasmic reticulum
- this causes the SR to release even more Ca2+
- this is calcium induced calcium release
- Ca2+ binds to troponin causing the conformational change that allows tropomyosin to move and unblick
when does contraction of the cardiomyocyte begin and end with reference to the graph
half way through the plateau phase and continues until the end of that phase
because of the plateau, cardiac muscle stays contracted longer than skeletal muscle
what is the route of cardiac electrical conduction?
- SA node across the atria (bachmann’s bundle)
- across the atria down to the AV node
- AV node delays impulse by 100-200 ms to allow the atria to empty
- impulse travels from AV node down the bundle of His
- Bundle of His divides into:
- Left bundle
- there’s left posterior and left anterior bundles too
- Right bundle
- Left bundle
- On all sides purkinje fibres project up from the apex
How long is the cardiac cycle?
0.8 seconds long
how much of the cardiac cycle is systole and how much is diastole
systole: 1/3
diastole: 2/3
when does systole begin with realation to the ECG and when does it end?
- Begins at the peak of the QRS complex (when isovolumetric contraction begins)
- Ends when the aortic valve closes - this is ~ the end of the T wave
when do the atria fill?
- blood is constantly dripping into the atria
- during ejection they are filling
- then during the majority of diastole blood is dripping straight through into the ventricles
Label the ECG
ECG normal timings
- P wave: 0.08-0.1
- QRS complex: 0.08-0.12 seconds
how much of the blood’s circulation is in veins at any one point?
70%
why do veins need a low pressure?
so that they can draw arterial blood through the capillaries
this is why being compliant is important for them
Blood flow through organs
- Liver - 27%
- Kidneys - 22%
- Muscle - 12%
- Brain - 14%
What vessels are the highest pressure
arterioles
5 systems important for blood pressurea and circulation control
- autoregulation
- local mediators
- hormonal factors
- baroreceptors
- neural control
Myogenic autoregulation
- if pressure increases in resistance vessels (arterioles) and they are stretched they respond by contraction of the smooth muscle cells
- this reduces the size of the lumen
- occurs until the diameter is normalised
- they also dilate when blood pressure is low
- this system evens out unecessary changes in perfusion pressure
which tissues are good at myogenic autoregulation?
- Good
- Renal, cerebral and coronary
- Bad
- skin and muscle
- so if you need to concerve circulation then it’s the skin that suffers
local mediators of circulatory control
- vasoconstrictors
- endothelin-1
- vasodilators
- Hypoxia
- adenosine
- NO
- CO2
- H+
endothelin and NO are the main ones
circulating hormonal factors that control blood pressure and circulation
- vasoconstrictors
- angiotensin II
- vasopressin (ADH)
- vasodilators
- Arial Natriuretic Peptide
where are the Baroreceptors
- Primary
- aortic arch
- carotid sinus
- Secondary are in the
- veins
- myocardium
- pulmonary vessels
How do baroreceptors work ?
- their firing rate is proportional to the PP and the MAP
- increased pressure causes them to fire more
- these impulses are sent to the medulla and response to lower BP is initiated
- increased stimulation of parasympathetic innervation of the heart
- Vagus and Ach
- decreased stimulation of sympathetic nervous system
- increased stimulation of parasympathetic innervation of the heart
- this causes lowered cardiac output as well as lowered total peripheral resistance
- BP falls
- Reverse happens for low blood pressure
baroreceptors in hypertensive patients
- after a few days away from normal blood pressure, baroreceptors adapt to normal baseline
- so baroreceptors are useful in the short term but do little in controlling blood pressure long term
Neural control
- most important tool for control of blood pressure
- main neural influences on the medulla are from baroreceptors
- The medulla
- pressor region: sympathetic raising of the blood pressure
- vasoconstriction
- increased cardiac output (inc heart rate and stroke volume)
- depressor region: parasympathetic lowering of blood pressure
- it does this by inhibiting the pressor region
- it also parasympathetically innervates the heart via the vagus
- pressor region: sympathetic raising of the blood pressure
what is hyperaemia
The increase of blood flow
what is preload
- the amount of filling of the ventricles
- increased by anything that increases ventricular filling or stretch of cardiac muscle
- i.e. aortic stenosis or ventricular systolic failure
- Decreased by anything that reduces stretch or ventricular filling
- i.e. mitral or tricuspid valve stenosis or atrial fibrilation
what is afterload
- this is the pressure aginst which the heart must work to eject blood during systole
- increased afterload decreases stroke volume
- depends on ABP and thickness of the ventricles
what is end diastolic volume
this is the volume of blood in the ventricles at the end of diastole
what is end systolic volume
- end systolic volume is the volume of blood left in the ventricle at the end of systole
what is stroke volume
- this is the amount of blood pumped by the left ventricle into the aorta with each ventricular contraction
- this is about 2/3 of the EDV
- SV = EDV - ESV
Frank Starling’s law of the heart:
- if all other factors remain constant SV will increase in response to an increased EDV
- this is due to the length tension relationship of muscle
- so if there’s more blood in the ventricle, the ventricle will be more stretched and as a result will contract more forcefully
- this doesn’t work forever - sometimes the heart becomes so stretched that it fails
what is contractility
this is the force of heart muscle contraction - it is independent of sarcomere length
what is elasticity
the tendancy for the heart to recoil following removal of a distending force (ventricular filling)
it is directly related to compliance
what is compliance?
- this is the ability of a tissue to resist recoil to its original dimensions on application of a distending force without allowing the pressure to increase a lot
- directly related to elasticity
- C = change in volume / change in pressure
- blood vessels with a higher compliance are more likely to deform
- veins
what is resistance
- this is the resisting force that must be overcome in order to push blood around the circulation and create flow
what is total peripheral resistance
- this is aka systemic vascular resistance
- it is the total resistance offered by the entire vascular system
Cardiac output equation
- Cardiac output = heart rate / stroke volume
what is normal cardiac output
5L/minute
Blood pressure equation
blood pressure = cardiac output x total peripheral resistance
what is pulse pressure
this is the systolic pressure minus the diastolic pressure
what is mean arterial pressure
MAP = diastolic pressure + 1/3 pulse pressure
MAP = CO x TPR
Ohm’s law
flow = change in pressure / resistance
what is left ventricular filling pressure
this is the pressure that builds up in the ventricle as the ventricle is being filled with blood
cardiac compensatory mechanisms during heart failure
- frank starling mechanism
- chronic ventricular dilation or hypertrophy
- tachycardia
autonomic compensatory mechanisms during heart failure
- increased sympathetic adrinergic activity
- reduced vagal activity to the heart
Hormonal compensatory mechanisms during heart failure
- renin - angiotensin - aldosterone system
- vasopressin (ADH)
- circulating catecholamines
- Dopamine, epinephrine (adrenaline), and norepinephrine
- Natriuretic peptides
draw and label the heart tube and its bulges
what does the bulbus cordis give rise to
- the right ventricle
- the outflow tracts of the left and right ventricle
- i.e. the proximal aorta and the pulmonary trunk
what does the primordial ventricle give rise to?
the left ventricle
what does the primordial atrium give rise to?
- left atrium
- anterior portion of right atrium
- left and right auricles
what does the sinus venosus give rise to ?
- the right atrium
- the vena cava
- the coronary sinus
what does the aortic sac give rise to
the aorta and the pulmonary artery
on what day does the heart begin to beat
22
what is the truncus arteriosus
it is the primitive common outflow tract of the heart - it goes on to develop into the ascending aorta and the pulmonary trunk
what are the endocardial cushions
- when the heart is basically just a curly tube blood enters the common atria, travels through the atrioventricular canal and exits the ventricles through the truncus arteriosus
- endocardial cushions grow at the sides of the AV canal and begin to partition it into two seperate openings
- the right and left AV canals are formed
formation of the aorta and the pulmonary artery
- at the end of the 4th week a muscular septum grows up from the floor of the ventricle
- an opening remains between the top of the septum and the bottom of the fused endocardial cushions
- this is called the interventricular foramen
- a spiral shaped septum called the aorticopulmonary septum grows up the truncus arteriosus and divides it
- this forms the aorta and the pulmonary trunk
- the aorticopulmonary septum grows down to fuse woth the cushions and the ventricular septum
- the fusion of these three elements of the septum happens by week 8
what do the first and second aortic arches become
they become minor arteries in the head
what do the 3rd aortic arches become
these become the right and left common carotids
what do the 4th aortic arches become
- the right becomes part of the right subclavian
- the left becomes part of the aortic arch
what do the 6th aortic arches become
they become the pulmonary arteries
Foetal circulation
- oxygenated blood from the placenta enters the foetus in the umbilical vein
- it bypasses the liver in the ductus venosus (later the ligamentum venosum) and enters the inferior vena cava
- here it combines with deoxygenated blood
- this blood enters the right atrium (along with SVC)
- most of this is then shunted into the foramen ovale
- any remaining blood that does enter the pulmonary artery will then be shunted into the aorta via the ductus arteriosus
- deoxygenated blood returns to the placenta via the umbiliacal arteries originating from the internal iliacs near the bladder
the first breath
- the sudden oxygenation of the lungs causes the vasodilation of the respiratory system
- this massively reduces the pressure in the pulmonary circulation
- this causes the pressure in the right side of the heart to drop relative to the left
- the foramen ovale snaps shut
- within 3 months it has fused and produced the fossa ovalis
- the umbilical vein constricts and forms the ligamentum teres
- umbilical arteris constrict and form the medial umbilical ligaments
- the ductus arteriosus constricts and forms the ligamentum arteriosum
- the ductus venosus constrics and forms the ligamentum venosum
Where does the SVC drain into
the right atrium at the 3rd rib
what is the surface marking for the apex of the heart?
the 5th intercostal space in the mid-clavicular line
how many people are right left and codominant
- 70% right dominant
- 10% left dominant
- 20% codominant
dependant on which coronary artery supplies the posterior interventricular artery
what does the posterior interventricular artery supply
it supplies the AV node
papillary muscles
- these attach to codi tendini
- cordi tendini attach to the cusps of the AV valves
- the papillary muscles contract during systole to prevent backflow of blood back into the atria
how many cusps do the semi-lunar valves have
- they have 3
- these are the aortic and pulmonary valves
what is ANP and what does it do
- atrial natriuretic peptide is secreted by atrial myocytes when they get stretched
- it promotes the excretion of water and sodium and potassium by the kidney
- it inhibits the secretion of renin
what are the two types of platelet granule
- alpha granules containing:
- clotting factors including fibrinogen
- platelet derived growth factor
- delta granule (aka dense bodies) containing:
- ADP
- Calcium
- Serotonin
- these are all platelet activating factors
