Case 4 Flashcards
1
Q
what is clinical heart failure
A
a state in which the cardiac output fails to meet the body’s demands. extracellular fluid composition and movement off fluid between compartments
2
Q
what is the extracellular fluid divided into
A
plasma and interstitial
3
Q
how much of the body is made up of fluid
A
60%
4
Q
what are the two phases of fluid movement
A
- the blood and associated plasma
2. movement from capillaries into interstitial fluid or space
5
Q
what is the composition of ECF
A
- na+
- cl-
- HCO3-
- glucose
6
Q
how much of the ECF is plasma
A
1/5
7
Q
how far away are cells in the body from capillaries
A
50um
8
Q
How do water molecules pass through the capillary
A
pores and will include ions like sodium and chloride
9
Q
how does water move
A
area of high concentration to an area of low concentration
10
Q
what does the capillary pressure do
A
tends to drive fluid out from the capillary
11
Q
what is capillary pressure opposed by
A
interstitial fluid pressure which Is usually lower and in fact is sub atmospheric
12
Q
what does capillary pressure push out
A
water
13
Q
what does colloid pressure do
A
pulls water into the capillary
14
Q
what pulls water into the capillary
A
plasma proteins, largely albumin pulling water towards them
15
Q
what is colloid pressure opposed by
A
interstitial fluid colloid pressure
16
Q
how big is the interstitium
A
1/6 of the body’s volume,e
17
Q
what has the interstitium got in it
A
loosely packed proteins, things like collagen fibre bundles and proteoglycan filaments
18
Q
what consistency is the interstitium
A
gel like consistency
19
Q
components of intracellular fluid compartment
A
- K+
- Mg++
- Phosphates
- Proteins
20
Q
why do proteins draw on ions such as sodium and potassium
A
because proteins are negatively charged and sodium and potassium are positively charged and water follows them into the cell
21
Q
what is required for active transport
A
kinetic energy
22
Q
what molecules can cross the lipid bilayer freely
A
fat soluble molecules
23
Q
what channel proteins transport water into the cell
A
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
24
Q
what are the factors impacting diffusion
A
- concentration
- charge - ions are negatively charged and inside membrane is positively charged.
- pressure affects movement of substances (capillaries and interstitial space)
25
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.
26
what is the rate limiting factor in facilitated diffusion
the carrier protein needs to change shape twice
27
what is the max rate of transportation denoted as
Vmax
28
how many potassiums does the Na-K-ATPase pump bind to
2 potassiums
29
how man sodiums does the Na-K-ATPase pump bind to inside the cell
3 sodiums
30
what activates the ATP pump
binding of potassium and sodium
31
what is the ATP pump function
breaks down adenosine triphosphate which is a high energy phosphate substance
32
what does the ATP pump break adenosine triphosphate into
adenosine diphosphate and a phosphate ion
33
what does the ATP pump release
energy
34
does the ATP channel go under a conformation change by using energy
yes
35
what does the conformational change do in the ATP pump
makes 3 sodium leave the cell and 4 potassium enter the cell
36
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
37
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
38
what 3 things regulate the cardiac output
Frank Sterling, Autonomic nervous system, endocrine system also
39
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
40
what is the neurohormonal response to a reduced cardiac output
- sympathetic nervous system
- RAAS
- ADH
41
What receptors detect low blood pressure
baroreceptors
42
where are the baroreceptors found
aortic arch and carotid Sinus
43
which nerves do the baroreceptors send signals via
the vagus and glossopharyngeal nerves
44
when the vasomotor sends signals to the heart to increase heart rate how many times is the cardiac output increased
2-3 fold
45
what else does sympathetic activation cause
innervates the vasculature and causes vasoconstriction in the arteries and veins and also increases the blood pressure
46
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
47
what does angiotensinogen form
angiotensin 1
48
what does angiotensin II lead to
- renal retention of salt and water
- vasoconstriction
- angiotensinase
49
what enzyme converts angiotensin I to angiotensin II
ACE
50
where is ADH released from
posterior pituitary
51
what does ADH result in
fluid retention, thirst and dilution of the blood
52
what does activation of SNS in heart attack lead to
increased heart rate and increased myocardial contractility
53
what do SNS and RAAS lead to
vasoconstriction
54
what do AHD and RAAS lead to
ECF expansion
55
what causes natriuretic peptides
increased myocardial stretch
56
example of a natriuretic peptide
BNP
57
function of BNP
passes sodium into urine which causes loss of salt and water which counteracts fluid expansion
58
what does BNP cause
vasodilation - counteracts vasoconstriction which is damaging to heart in long run
59
what is maladaptive process
chronic fluid retention
60
what does chronic fluid retention lead to
1. no further improvement in the cardiac output
2. increased workload on already damaged heart
3. pulmonary and peripheral oedema
61
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
62
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
63
what does chronic sympathetic activation cause
1. increased energy demand
2. vasoconstriction: increased after load
3. worsening schema
4. apoptosis/necorisis of heart cells
64
what does chronic RAAS activation lead to
1. hypertrophy of heart muscle
2. fibrosis
3. apoptosis
65
what gets rid of the fluid overload
diuretics
66
which layer is the heart formed in
the mesoderm
67
what does the ectoderm give rise to
skin and neural tissues
68
what does the mesoderm give rise to
most of the muscles
69
what does the endoderm give rise to
internal organs like GI tract
70
where is heart development visible
ventral surface
71
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
72
development of cardiac stages
- cardiac cell fate acquired
| - angiogenic cells located in cariogenic plate - cranial and lateral to neural plates
73
when is cardiac crescent developed
at 15 days post fertilisation
74
what are the two heart fields
primary and secondary
75
what is different about the secondary heart fields
they move into the heart and contribute to outflow tract and right ventricle cardiac structures
76
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
77
when does linear heart tube form
21 days
78
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
79
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
```
80
when does cardiac looping occur
23-24 days
81
what does cardiac looping do
brings atria more upwards and behind the presumptive ventricle.
82
what shape is cardiac looping
dextral C-shape loop
83
what is heterotaxy
reversed orientation. if it happens to all organs - situs inversus then not necessarily pathological
84
when does septation occur
weeks 4-9
85
when does atrial septation occur
between 6th and 8th week post fertilisation
86
are atrial septal defects asymptomatic
yes
87
what does the foramen ovale do
allows transmission of blood between the right and left atrium. blood bypass the lungs
88
what does the foremen ovale turn into
fossa ovalis
89
how many people have a patent foremen ovale
10-20% of adults
90
when does ventricular septation occur
7th to mid 9th wee
91
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
92
what is the failure of separation of the aorta and pulmonary artery called
persistent truncus arterioisus
93
what is a PTA
single artery arising from both ventricles
94
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
95
what layer of the heart is the epicardium
outer epithelial layer of the heart
96
what does the epicardium form from
precursor called proepicardium located below heart
97
what to epicardial cells differentiate into
coronary smooth muscle, myocardial fibroblasts
98
when are heart chambers and major vessels formed by
the 8th week
99
what does ductus arterioisus do
connects pulmonary artery to aortic arch
100
what does the ductus arteriosus form after birth
ligamentum arteriosum
101
what promotes the closure of the ductus aeteriosus
increase in neonatal blood oxygen content and withdrawal of maternal prostaglandins promote closure
102
how popular is patent ductus arterioles
occurs in 8/1000 premature births. 2/1000 full term births
103
ratio of live births affected by congenital heart defects
1:125
104
what is deletion syndrome
22q11.2 deletion syndrome
105
how common is 22q11.2 syndrome
1 in 4000 births
106
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
107
how many CHD patients survive into adulthood
90%
108
what does P wave show
depolarisation of the atria
109
what does QRS complex show
depolarisation of the ventricles
110
what does the T wave show
repolarisaion of the ventricles
111
where are V1 and 2 placed
right ventricle
112
where are V3 and 4 placed
ventricular septum
113
where are V5 and 6 placed
anterior and lateral wall left ventricle
114
what lead is overall direction
lead one
115
overall direction of electricity is which lead
lead 3
116
overall activity electric is which lead
lead 2
117
what does atrial fibrillation look like on an ECG
no P waves
118
how often does the heart beat per day
70bpm
119
what are the contractile working cells of the heart
the cardiac myocytes
120
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
121
size of cardiomyoctres
approx 100mmx20mm
122
how much of Total cell number are cardiomyoctes
30-40%
123
what transmit ionic currents from one cell to another
gap junctions
124
what are gap junctions made uo of
six connexin sub-units which form a hollow tube known as a connexon
125
what glues the cells together
desmosomes
126
what spans the gap between the cell membranes
glycoproteins called cadherins and design form the intermediate filaments
127
sarcolemma
membrane surrounding the cardiomyocyte
128
what are the contractile proteins
actin and myosin
129
what is the contractile unit of the cardiomyocye
sarcomere
130
what are attached to the actin filaments
Z-lines
131
what are the thick filaments
myosin
132
what colour do alpha actinic Z lines turn
green
133
what colour do connexin 43 gap junctions tuen
blue
134
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
135
why does systolic Ca2+ have to be high
to activate the contractile machinery in order to pump blood from the heart
136
what triggers contraction
a rise in intracellular ca2+ in the cardiomyocte
137
what is an action potential
transient depolarisation of a cell as a result of an ion channel activity
138
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
139
how is the intracellular calcium concentration regular;ared
excitation-contraction coupling
140
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
141
what is the cardiac cycle
the relationship between ventricular pressure and volume
142
what is a murmur
abnormal blood flow across the heart valve or across a structure within the heart
143
how is heart murmur diagnosed
auscultate and also can pick up with an echocardiogram
144
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
145
what are reasons for aortic stenosis
- most commonly because of degenerative aortic valve disease
| - secondly because being born with a bicuspid aortic valve
146
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
147
what is corrigans sign
neck pulsation
148
what is Beckers sign
retinal vessel pulsation
149
what is de mussets sign
head bobbing in time with cardiac cycle
150
what is duroziezs sign
diastolic murmur heard over femoral pulses when partly occluded below stethoscope
151
what is muellers sign
uvula pulsation
152
what is quinces sign
capillary pulsation in nail bed
153
what is traubes sign
pistol shot systolic sound in femoral arteries
154
what is endocarditis
infection of the heart valve
155
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
156
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
157
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
158
why is potassium such an important electrolyte
98% of K+ is inside cell
159
what is normal range of potassium
3.5-5mM
160
what happens when potassium gradient is disrupted
hyperkalemia
161
what is hypokalaemia
low plasma K+ ( usually due to diuretics and excessive loss in urine)
162
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
163
what equation is used to find potassium gradient
Nernst equation
164
what is the inactivation gate
h gate
165
what is the activation gate
m gate
166
is closure of h gate slow or fast
very slow
167
what happens when h gate is closed
it is inactivated
168
what are ion channels to stimulation
refractory
169
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
170
how are 4 domains linked
convalelty
171
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
172
structure of inward rectifier K+ channels
- two transmembrane domains and pore forming loop
173
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
174
what contributes to resting membrane potential
amount of negative charge needed to balance the concentration of K+ ion gradient is the equilibrium potential
175
what happens to electrodes when there is an impermeable membrane
they will read 0
176
what does Nernst equation predict K+ value of
-86mV
177
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,
178
what is equilibrium potential of Na+
around 70mV
179
what is the rate of depolarisation - phase 0 determined by
rate which Na enters the cell.
180
what are phases 1 and 3 of action potential brought about by
potassium channels
181
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.
182
what is phase 2 brought about by
L-type calcium channels
183
what does phase 3 include
delayed rectifier potassium channels.
184
what day does foetus first heartbeat occur
day 22
185
where is the ostium secondum located
in the septum primum
186
what are the two proteins involved in atrial fibrillation
Matrix metaloproteinases and Disintegrin
187
Phospholambn regulates what in the process of cardiocytes relaxation?
SERCA pump
188
The 2nd
| heart sound represents
Aortic and pulmonary valve closure
189
The pressure in the left ventricle after ventricular diastole is the:
preload
190
Furosemide acts primarily on what structure of the body
Ascending loop of Henlé in the kidney
191
What is ‘Cor Pulmonale’
right sided heart failure
192
Brain natriureti
| c peptide is released in response to what
cardiac muscle stretch
193
what is the syncytium
fusion of the nuclei
194
how much additional filling does atrial contraction cause
20%
195
What is the after load
pressure in the artery leading from the ventricle against which the ventricle must collapse
196
does the SA node have contractile muscle filaments
no
197
what factors that affect venous return
- right atrial pressure
- systemic filling pressure
- resistance to venous return
198
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
198
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
199
most common reason for right sided heart failure
left sided heart failure
200
BNP make up
32 amino acid polypeptide
201
what is rheumatic fever
group A streptococcal pharyngitis
202
what layers of the heart does RF affect
all three
203
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
204
what do translators do
written
205
what to interpreters do
spoken
206
what is disease of valvular degeneration
myxomatous disease
