Case 4 Flashcards
what is clinical heart failure
a state in which the cardiac output fails to meet the body’s demands. extracellular fluid composition and movement off fluid between compartments
what is the extracellular fluid divided into
plasma and interstitial
how much of the body is made up of fluid
60%
what are the two phases of fluid movement
- the blood and associated plasma
2. movement from capillaries into interstitial fluid or space
what is the composition of ECF
- na+
- cl-
- HCO3-
- glucose
how much of the ECF is plasma
1/5
how far away are cells in the body from capillaries
50um
How do water molecules pass through the capillary
pores and will include ions like sodium and chloride
how does water move
area of high concentration to an area of low concentration
what does the capillary pressure do
tends to drive fluid out from the capillary
what is capillary pressure opposed by
interstitial fluid pressure which Is usually lower and in fact is sub atmospheric
what does capillary pressure push out
water
what does colloid pressure do
pulls water into the capillary
what pulls water into the capillary
plasma proteins, largely albumin pulling water towards them
what is colloid pressure opposed by
interstitial fluid colloid pressure
how big is the interstitium
1/6 of the body’s volume,e
what has the interstitium got in it
loosely packed proteins, things like collagen fibre bundles and proteoglycan filaments
what consistency is the interstitium
gel like consistency
components of intracellular fluid compartment
- K+
- Mg++
- Phosphates
- Proteins
why do proteins draw on ions such as sodium and potassium
because proteins are negatively charged and sodium and potassium are positively charged and water follows them into the cell
what is required for active transport
kinetic energy
what molecules can cross the lipid bilayer freely
fat soluble molecules
what channel proteins transport water into the cell
aquaporines, they have a pore inside them which allows water molecules to traverse the cell membrane in single file. red blood cell has aquaporins in it
what are the factors impacting diffusion
- concentration
- charge - ions are negatively charged and inside membrane is positively charged.
- pressure affects movement of substances (capillaries and interstitial space)
what is the protein involved in facilitated diffusion
carrier proteins that are specific to substances and bind, allowing them to diffuse form one side of the membrane to another after going through a conformational change.
what is the rate limiting factor in facilitated diffusion
the carrier protein needs to change shape twice
what is the max rate of transportation denoted as
Vmax
how many potassiums does the Na-K-ATPase pump bind to
2 potassiums
how man sodiums does the Na-K-ATPase pump bind to inside the cell
3 sodiums
what activates the ATP pump
binding of potassium and sodium
what is the ATP pump function
breaks down adenosine triphosphate which is a high energy phosphate substance
what does the ATP pump break adenosine triphosphate into
adenosine diphosphate and a phosphate ion
what does the ATP pump release
energy
does the ATP channel go under a conformation change by using energy
yes
what does the conformational change do in the ATP pump
makes 3 sodium leave the cell and 4 potassium enter the cell
why does the inside of the cell membrane become negatively charged in ATP channel
there is a net loss of one positive ion every time
what does losing one sodium ion result in in the ATP pump channel
allows some water to follow it from the inside to outside of the cell. partly responsible for it not bursting
what 3 things regulate the cardiac output
Frank Sterling, Autonomic nervous system, endocrine system also
cascade of events if patient has a heart attack and develops important amounts of damage to left ventricle
Left ventricle pumps blood to the systemic circulation normally, so if there is significant amount of damage to it, this will reduce the amount blood it pumps and reduce the cardiac output
Output of the heart will not be sufficient to reach body’s needs (stroke volume)
Causes a reduction in systemic blood pressure which the body will sense
Because forward force is reduced, the heart is not getting rid of the blood that is inside the left ventricle
The blood is stagnating there and makes it difficult for blood to enter the left ventricle because forward flow is poor
This cause the pressure in the left atrium to increase, which normally of loads its blood into the left ventricle
Blood that wants to return into the left atrium from the lungs also struggles to enter as pressure is increased
Creates a back flow of pressure
The right ventricle is pumping against an increased pressure, and the right atrium is also increased in pressure
Difficult for blood to return into the heart from inferior and superior vena cava because of pressure in right ventricle
what is the neurohormonal response to a reduced cardiac output
- sympathetic nervous system
- RAAS
- ADH
What receptors detect low blood pressure
baroreceptors
where are the baroreceptors found
aortic arch and carotid Sinus
which nerves do the baroreceptors send signals via
the vagus and glossopharyngeal nerves
when the vasomotor sends signals to the heart to increase heart rate how many times is the cardiac output increased
2-3 fold
what else does sympathetic activation cause
innervates the vasculature and causes vasoconstriction in the arteries and veins and also increases the blood pressure
RAAS mechanism
- renin is released by the kidneys in response to decreasing blood pressure
- vasoconstriction
- salt and water retention increases circulating volume in the body
- chronic activation results in progressive water retention
- increasing circulating volume should increase stretch of the heart muscle
what does angiotensinogen form
angiotensin 1
what does angiotensin II lead to
- renal retention of salt and water
- vasoconstriction
- angiotensinase
what enzyme converts angiotensin I to angiotensin II
ACE
where is ADH released from
posterior pituitary
what does ADH result in
fluid retention, thirst and dilution of the blood
what does activation of SNS in heart attack lead to
increased heart rate and increased myocardial contractility
what do SNS and RAAS lead to
vasoconstriction
what do AHD and RAAS lead to
ECF expansion
what causes natriuretic peptides
increased myocardial stretch
example of a natriuretic peptide
BNP
function of BNP
passes sodium into urine which causes loss of salt and water which counteracts fluid expansion
what does BNP cause
vasodilation - counteracts vasoconstriction which is damaging to heart in long run
what is maladaptive process
chronic fluid retention
what does chronic fluid retention lead to
- no further improvement in the cardiac output
- increased workload on already damaged heart
- pulmonary and peripheral oedema
mechanism of oedema
- back flow of pressure and venous pressures eventually increase causing an increase in the capillary pressure which will tend to cause more fluid to filtrate out of the capillaries
- also more circulating volume, salt and water retention, which will again cause more fluid to cross capillary membrane
why is oedema common in lower limbs
- elevated venous pressure in legs due to gravity
- pressure also elevated in the capillaries leading to leakage of fluid into the tissue spaces (oedema)
- lowest limbs have highest capillary pressure
what does chronic sympathetic activation cause
- increased energy demand
- vasoconstriction: increased after load
- worsening schema
- apoptosis/necorisis of heart cells
what does chronic RAAS activation lead to
- hypertrophy of heart muscle
- fibrosis
- apoptosis
what gets rid of the fluid overload
diuretics
which layer is the heart formed in
the mesoderm
what does the ectoderm give rise to
skin and neural tissues
what does the mesoderm give rise to
most of the muscles
what does the endoderm give rise to
internal organs like GI tract
where is heart development visible
ventral surface
cardiac development summary
cardiac development begins with the initiation of structures called heart fields
These heart fields then converge at the midline of the embryo to form something called the cardiac crescent which assort of an ’n’ shaped structure in the embryo
Those cardiac crescent cells come together to form a linear heart tube
That tube goes under a series of morphological changes called looping so that it takes on the correct position within the embryo
It then further subdivides into the different chambers and we can see structures such as the cardiac cushions, form the valves, begin to develop within that tube
We also get grooves forming on the surface of the tube which will represent the premature or primitive formation of the chambers
Following these events we get the formation of the great vessels and the heart acquires the anatomy it needs for the adult
development of cardiac stages
- cardiac cell fate acquired
- angiogenic cells located in cariogenic plate - cranial and lateral to neural plates
when is cardiac crescent developed
at 15 days post fertilisation
what are the two heart fields
primary and secondary
what is different about the secondary heart fields
they move into the heart and contribute to outflow tract and right ventricle cardiac structures
cardiac crescent fusion
- cardiac crescent fuses at the mid-line to form the cardiac tube
- elongate at the midline of the embryo
- forms primary heart tube
when does linear heart tube form
21 days
where are ventricles and atria located in heart tube
developing ventricles are situated more cranial. atria is at the bottom of the tube and ventricle is in the mid region
what are the heart tube structures in order from top to bottom
1 dorsal aorta 2 aortic sac 3 bulbus cordis 4 primitive ventricle 5 atrioventricular sulcus 6 primitive atria 7 sinus venous
when does cardiac looping occur
23-24 days
what does cardiac looping do
brings atria more upwards and behind the presumptive ventricle.
what shape is cardiac looping
dextral C-shape loop
what is heterotaxy
reversed orientation. if it happens to all organs - situs inversus then not necessarily pathological
when does septation occur
weeks 4-9
when does atrial septation occur
between 6th and 8th week post fertilisation
are atrial septal defects asymptomatic
yes
what does the foramen ovale do
allows transmission of blood between the right and left atrium. blood bypass the lungs
what does the foremen ovale turn into
fossa ovalis
how many people have a patent foremen ovale
10-20% of adults
when does ventricular septation occur
7th to mid 9th wee
AV valve formation
- endocardial cushions precursors of the valves
- important to prevent back flow
- protrude into the heart tubes
- mid 7th to 8th week post fertilisation
what is the failure of separation of the aorta and pulmonary artery called
persistent truncus arterioisus
what is a PTA
single artery arising from both ventricles
what are the semilunar valves
the division between left ventricle and aorta and the division between the right ventricle and the pulmonary artery. prevent backflow
what layer of the heart is the epicardium
outer epithelial layer of the heart
what does the epicardium form from
precursor called proepicardium located below heart
what to epicardial cells differentiate into
coronary smooth muscle, myocardial fibroblasts
when are heart chambers and major vessels formed by
the 8th week
what does ductus arterioisus do
connects pulmonary artery to aortic arch
what does the ductus arteriosus form after birth
ligamentum arteriosum
what promotes the closure of the ductus aeteriosus
increase in neonatal blood oxygen content and withdrawal of maternal prostaglandins promote closure
how popular is patent ductus arterioles
occurs in 8/1000 premature births. 2/1000 full term births
ratio of live births affected by congenital heart defects
1:125
what is deletion syndrome
22q11.2 deletion syndrome
how common is 22q11.2 syndrome
1 in 4000 births
what happens in 22q11.2 syndrome
TBX1 loss contributes to cardiac defect phenotypes
TBX1 expressed in secondary heart field which gives rise to outflow tract
loss of TBX1 causes shortening of the outflow tract lacking septation
how many CHD patients survive into adulthood
90%
what does P wave show
depolarisation of the atria
what does QRS complex show
depolarisation of the ventricles
what does the T wave show
repolarisaion of the ventricles
where are V1 and 2 placed
right ventricle
where are V3 and 4 placed
ventricular septum
where are V5 and 6 placed
anterior and lateral wall left ventricle
what lead is overall direction
lead one
overall direction of electricity is which lead
lead 3
overall activity electric is which lead
lead 2
what does atrial fibrillation look like on an ECG
no P waves
how often does the heart beat per day
70bpm
what are the contractile working cells of the heart
the cardiac myocytes
what is the role of the cardiomyocyte
to contract in unison in order to provide effective pump action to ensure adequate blood perfusion of the organs and tissues
size of cardiomyoctres
approx 100mmx20mm
how much of Total cell number are cardiomyoctes
30-40%
what transmit ionic currents from one cell to another
gap junctions
what are gap junctions made uo of
six connexin sub-units which form a hollow tube known as a connexon
what glues the cells together
desmosomes
what spans the gap between the cell membranes
glycoproteins called cadherins and design form the intermediate filaments
sarcolemma
membrane surrounding the cardiomyocyte
what are the contractile proteins
actin and myosin
what is the contractile unit of the cardiomyocye
sarcomere
what are attached to the actin filaments
Z-lines
what are the thick filaments
myosin
what colour do alpha actinic Z lines turn
green
what colour do connexin 43 gap junctions tuen
blue
what do the T-tubules do
transmit electrical stimulus rapidly into the interior of the cell to promote the synchronous activation of the whole depth of the cell despite the fact that the signal to contract is relayed across the external membrane
why does systolic Ca2+ have to be high
to activate the contractile machinery in order to pump blood from the heart
what triggers contraction
a rise in intracellular ca2+ in the cardiomyocte
what is an action potential
transient depolarisation of a cell as a result of an ion channel activity
relationship between action potential and contraction
1 voltage gated sodium channels open
2 Na+ inflow depolarises the membrane and triggers the opening of still more Na+ channels creating a positive feedback cycle and a rapidly rising membrane voltage.
3 Na+ channels close when the cell depolarises and the voltage peaks at nearly +30mV
4 Ca2+ entering through slow calcium channels prolongs the depolarisation of the membrane causing a plateau. plateau falls slightly because of some K+ leakage
5 Ca2+ channels close and Ca2+ is transported out of the cell. K+ channels open and rapid K+ outflow returns membrane to its resting potential
how is the intracellular calcium concentration regular;ared
excitation-contraction coupling
contractile mechanism
- when calcium binds to cTnC it induces a rearrangement in the troponin-tropomyosin complex
- movement of tropomyosin exposes a myosin binding site on actin resulting in cross bridge formation and shortening of the sacromere
what is the cardiac cycle
the relationship between ventricular pressure and volume
what is a murmur
abnormal blood flow across the heart valve or across a structure within the heart
how is heart murmur diagnosed
auscultate and also can pick up with an echocardiogram
aortic stenosis
aortic valve becomes heavily calcified with reduced opening so you can see the valve becomes thickened
Left ventricle has to become hypertrophy so has to push harder and harder
You get a muscley left ventricle, it doesn’t become bigger so you don’t get apical displacement
Thrusting apex
Abnormal blood flow is during systole because its when the heart is pumping
When blood is becoming turbulent and churned up by that thickened aortic valve
Systolic murmur and that is what we call a crescendo decrescendo
also would expect a low pulse pressure in severe cases
Second intercostal space mid clavicular line
what are reasons for aortic stenosis
- most commonly because of degenerative aortic valve disease
- secondly because being born with a bicuspid aortic valve
aortic regurgitation
blood falls back into left ventricle during diastole
Diastolic murmur and difficult to hear
lub-dub-ahhh
Volume loading of the ventricle
Causes a dilatation of the left ventricle and displaced apex
Loudest on left sternal edge with evidence of apical displacement towards the axillary
Rapid downslope of the pulse, and when you feel it at the pulse its called a collapse pulse
Visible pulsation of the neck vessels
what is corrigans sign
neck pulsation
what is Beckers sign
retinal vessel pulsation
what is de mussets sign
head bobbing in time with cardiac cycle
what is duroziezs sign
diastolic murmur heard over femoral pulses when partly occluded below stethoscope
what is muellers sign
uvula pulsation
what is quinces sign
capillary pulsation in nail bed
what is traubes sign
pistol shot systolic sound in femoral arteries
what is endocarditis
infection of the heart valve
mitral regurgitation
valve that sits between left aorta and ventricle
Instead of all blood going out of atrium during systole, blood flows back into the left atrium
systolic murmor
Hollow sytolic murmur; lub-wind-dub
Loudest in mitral area and radiate towards the axilla
Ventricle becomes volume loaded and apex becomes displaced
functional mitral regurgitation
stretch left ventricle - the valve leaflets are pulled apart ams there’s a whole during systole in the valve
ischameic MR also, flopping of the valve
Heart attack of artery that supplied papillary muscle
hypertrophic obstructive cardiomyopathy
Genetic thickening of the heart muscle and when heart is in systole, the mitral leaflet is dragged towards the septum causing a leak in the. Mitral valve
mitral stenosis
thickening of the mitral valve
Only cause really is rheumatic heart disease
mitral valve doesn’t open well and difficult to get blood into left ventricle
No problem with left ventricle - just not getting enough blood
Happening in diastole
why is potassium such an important electrolyte
98% of K+ is inside cell
what is normal range of potassium
3.5-5mM
what happens when potassium gradient is disrupted
hyperkalemia
what is hypokalaemia
low plasma K+ ( usually due to diuretics and excessive loss in urine)
how does K+ alter cellular excitability
membrane potential of the cell determines cellular excitability. membrane potential is largely set by the gradient of K+ across the cell membrane
what equation is used to find potassium gradient
Nernst equation
what is the inactivation gate
h gate
what is the activation gate
m gate
is closure of h gate slow or fast
very slow
what happens when h gate is closed
it is inactivated
what are ion channels to stimulation
refractory
basic Na+, Ca2+ channel structure
- made of four subunits
- each submit has 6 transmembrane spanning domains (S1-S6)
- connected by a series of intra and extracellular loops
- S4 is the end gate
- link between S5 and S6 is the pore forming loop
how are 4 domains linked
convalelty
are potassium channels covalently linked
no so therefore can come from different potassium channel families. this is why they are so diverse in their function. they have a H gate but more like ball and chain
structure of inward rectifier K+ channels
- two transmembrane domains and pore forming loop
what is Kir function
conduct ions out of the cell. allow K+ to move from inside to outside the cell and that is what sets the membrane resting potential
what contributes to resting membrane potential
amount of negative charge needed to balance the concentration of K+ ion gradient is the equilibrium potential
what happens to electrodes when there is an impermeable membrane
they will read 0
what does Nernst equation predict K+ value of
-86mV
why is resting membrane potential around 80mV
Ik1 is open as this is letting potassium out of the cell so membrane at rest is permeable to potassium,
what is equilibrium potential of Na+
around 70mV
what is the rate of depolarisation - phase 0 determined by
rate which Na enters the cell.
what are phases 1 and 3 of action potential brought about by
potassium channels
what happens in phase 2 of action potential
- potassium going out but opening of calcium channels
- this allows systolic ejection and refractoriness to re-stimulation to allow time for ventricles to refill with blood before onset of next contraction. long action potential in the heart.
what is phase 2 brought about by
L-type calcium channels
what does phase 3 include
delayed rectifier potassium channels.
what day does foetus first heartbeat occur
day 22
where is the ostium secondum located
in the septum primum
what are the two proteins involved in atrial fibrillation
Matrix metaloproteinases and Disintegrin
Phospholambn regulates what in the process of cardiocytes relaxation?
SERCA pump
The 2nd
heart sound represents
Aortic and pulmonary valve closure
The pressure in the left ventricle after ventricular diastole is the:
preload
Furosemide acts primarily on what structure of the body
Ascending loop of Henlé in the kidney
What is ‘Cor Pulmonale’
right sided heart failure
Brain natriureti
c peptide is released in response to what
cardiac muscle stretch
what is the syncytium
fusion of the nuclei
how much additional filling does atrial contraction cause
20%
What is the after load
pressure in the artery leading from the ventricle against which the ventricle must collapse
does the SA node have contractile muscle filaments
no
what factors that affect venous return
- right atrial pressure
- systemic filling pressure
- resistance to venous return
what does the Frank Starling Mechanism state
that the stroke volume increases in response to an increase in the volume of blood filling the heart when all other factors reman constant
what does the Frank Starling Mechanism state
that the stroke volume increases in response to an increase in the volume of blood filling the heart when all other factors reman constant
most common reason for right sided heart failure
left sided heart failure
BNP make up
32 amino acid polypeptide
what is rheumatic fever
group A streptococcal pharyngitis
what layers of the heart does RF affect
all three
what is the characteristic lesion of rheumatic carditis
the Aschoff nodule which is a granulomatous lesion with a central nectroic area occurring in the myocardium. they are macrophages
what do translators do
written
what to interpreters do
spoken
what is disease of valvular degeneration
myxomatous disease
