week 1 Flashcards
1
Q
locations of heart valves
A
tricuspid - RA-RV
mitral/bicuspid - LA-LV
pulmonary - RV-PA
aortic - LV-aorta
2
Q
cardiac cycle
A
atrial systole
atrial diastole
ventricular systole
ventricular diastole
3
Q
function of atrial systole
A
atrial contraction forces small amount of additional blood into relaxed ventricles
4
Q
ventricular systole
A
first phase - ventricular contraction pushes AV valves closed but not enough pressure to open semilunar valves
second phase - ventricular pressure rises and exceeds pressure in arteries - S valves open and blood is ejected
5
Q
ventricular diastole
A
early - as ventricles relax, pressure here drops and blood flows back against s valves, forcing them shut - blood flows into relaxed atria
late - all chambers relaxed, ventricles fill passively
6
Q
positive inotropy
A
greater contraction
7
Q
cardiac output equation
A
CO = SV x HR
8
Q
BP equation
A
BP = CO x PVR
PVR is peripheral vascular resistance
9
Q
how is the membrane potential in cardiac cells maintained
A
Na+ and Ca2+ current inwards is depolarising - high conc outside cell
K+ current outwards repolarises - high conc inside
10
Q
action potential phases
A
0 - opening of voltage gated Na+ channels allowing Na+ inwards
1 - rapid membrane voltage dependent inactivation of I(Na) - activation of outward K+
2 (plateau phase) - balance of inward Ca2+ and outward K+
3 (repolarisation) - inward currents inactivated and outward K+ predominant
4 - resting
11
Q
excitation-contraction coupling
A
1 - membrane depolarisation
2 - this activates L type Ca channel
3 - Ca induced Ca release - RyR sits next to L type Ca channel in cell and sense local calcium - Ryr then opens and pours Ca from SR
4 - Ca binds to myofilaments initiating contraction
5 - relaxation - calcium released from SR goes back in and Ca from outside cell is pumped out of cell
6 - return to resting Ca levels
12
Q
where do coronary arteries arise
A
from base of aorta
13
Q
coronary arteries
A
left coronary artery splits to left circumflex and left anterior descending
left marginal artery from LCA
right coronary artery splits into posterior descending and right marginal
14
Q
how does blood get into coronary arteries
A
during diastole
blood travels back in aorta and down coronary arteries
15
Q
where to auscultate valves
A
aortic valve at 2nd-3rd right interspace
pulmonary valve - 2nd-3rd left interspace
tricuspid - left sternal border
mitral - apex
16
Q
what is phenylephrine
A
a1 adrenoreceptor agonist
causes powerful vasoconstriction
adrenaline and noradrenaline will stimulate normally
17
Q
what are the holes in the internal lamina for
A
endothelial cells can communicate with SMCs
remodelling reduces connection
18
Q
effect of pressure on vascular structure
A
vessel widens
wall gets thinner
vessel gets longer - SMCs are arranged in helical structure
systole - blood
19
Q
what is pulse wave velocity
A
velocity at which the blood pressure pulse propagates through the circulatory system
more springy, stretchy arteries will dampen wave making PWV lower
high PWV may be vascular stiffening
20
Q
main change to vessels in hypertension
A
hypertension results in vascular remodelling
remodelling characterised by increased media to lumen ratio - media thickens - lumen narrows
21
Q
how does blood vessel radius affect flow
A
small changes to radius have profound changes in flow - smaller radius will decrease blood slow
22
Q
how does blood vessel length affect flow
A
flow is linearly proportional to length
23
Q
how does hypertension affect angiotensin
A
increased in hypertension
it is a vasoconstrictor
GF causing SMCs to proliferate and migrate
24
Q
neurotransmitters in parasympathetic and sympathetic NS
A
p - preganglionic and postganglionic fibres use acetyl choline
s - preganglionic fibres use Ach and post use noradrenaline and adrenaline
sweat glands postganglionic fibres release Ach even in sympathetic NS
25
how do baroreceptors regulate BP
in carotid sinus and aortic arch
high pressure will give high stretch - brain initiates reduction in sympathetic drive to vessels - blood vessel diameter would increase
low stretch will mean low BP - brain increases sympathetic activity - constriction of vessels - increases resistance and so increases pressure
26
3 NTs expected in any sympathetic nerve (sympathetic triad)
neuropeptide y (NPY)
ATP
noradrenaline
needed for fine control and regulation
27
receptor of NPY in sympathetic nerve
y receptor
28
receptor of noradrenaline in sympathetic nerve
alpha and beta adrenoreceptors
29
receptor of ATP in sympathetic nerve
P2x receptor (ion channel)
30
causes of large vasoconstriction
increase sensitivity of receptors
more NT
drive high frequency activation - will release neuropeptide - gives big contraction
31
where are NTs in a nerve
synthesised in cell body, travel down axons
varacosities can take up NT and store them while they wait for release
AP travelling down nerve increases chance of NT release
32
what is perivascular adipose tissue
```
PVAT surrounds most large blood vessels and plays an important role in vascular homeostasis
can be pro or anti contractile
removing fat can damage vessel wall
sensory nerves are present
compounds from fat can influence nerves
```
33
what is an electrocardiogram (ECG)
a recording of the electrical activity of the heart from the skin
34
parts of an ECG wave
before P - impulse formation in SA node
p - atrial depolarisation
between p and q - delay at AV node while ventricles fill (after atria contraction)
q - conduction through bundle branches and purkinje fibres
qrs - ventricular depolarisation
ST segment - plateau phase of repolarisation - pretty electrically stable
t - final rapid repolarisation
35
where are the left ad right bundle branches
ventricular septum
36
what are ECG leads
not the wire attached to patient
| viewpoint we look at activity from - the electrical vector
37
two types of ECG lead
unipolar and bipolar leads
38
difference between bipolar and unipolar ECG leads
unipolar measures the potential variation at a single point
| bipolar measures potential difference between two points
39
unipolar leads
augumented limb leads - aVR, aVL, aVF
| chest leads - V1-V6
40
bipolar leads
limb leads I, II and III
I = between right arm and left arm
II = RA to left leg
III = LA to LL
41
inferior ECG leads
III, aVF and II
42
anterior ECG leads
V1-4
43
lateral ECG leads
aVL, I, V5-6
44
systematic approach to an ECG
```
always ask for clinical context
check the date, time and patient details
access technical quality eg paper speed
identify PQRST
measure HR with QRS
check ECG intervals
determine QRS axis
look at P, QRS, T morphology
can look at old ECGs to see progression
```
45
how to determine HR from ECG
300 divided by number of large squares between each QRS complex
1 square = 300/min as 300/1 = 300
2 squares = 150/min as 300/2 = 150
or
number of QRS complexes across ECG (10sec) x6
46
normal ranges for ECG intervals
PR interval - <1 large square, <200ms
QRS - <3 small squares, <120ms
QT interval - <11 small squares, <440ms
47
what is the QRS axis
direction of average depolarisation in heart
determined from limb leads
angle determined relative to lead I
normal is -30 to +90 degrees (+ve QRS in I and II)
axis is approximated by finding lead with most +ve QRS
48
abnormal QRS axis
left axis deviation - -30 to -90 degrees - positive QRS in I, negative in II and aVF
right axis deviation - +90 to +180 degrees - negative QRS in I, positive in aVF
extreme axis deviation - negative QRS in I and II, positive in aVR
49
normal P/QRS/T morphology
normal P wave is upright in inferior leads
ST segment is flat
T wave has same polarity as QRS
50
pleural effusion
build-up of excess fluid between the layers of the pleura outside the lungs
51
indications for using an echocardiogram
when structural imaging of one of the following is needed:
left or right ventricle and their cavities
valves
pericardium
atria and septa between cardiac chambers
great vessels
52
what is an echocardiogram
type of ultrasound scan
53
difference between a transthoracic and transesophageal echocardiogram
Transthoracic - noninvasive, taking place entirely outside your body
Transesophageal - guide a special ultrasound probe into your mouth and down your oesophagus behind LA after sedation - can get better pictures
54
what is a doppler echocardiogram
procedure that uses Doppler ultrasonography to examine the heart
the use of Doppler technology allows determination of the speed and direction of blood flow by utilizing the Doppler effect
55
what is cardiovascular resonance
CMR scan uses a strong magnetic field and radio waves to create detailed images of the heart
45-60 minute scan
56
when to use CMR
ischaemic heart disease, heart failure assessment, myocardial tissue characterisation, valvular heart disease, adult congenital heart disease, reference-standard LV and RV volumes
57
disadvantages of CMR
expensive
lengthy examination timwa
claustrophobia
patient co-operation eg for breath holds
58
what is late gadolinium enhancement
a technique used in CMR - gadolinium attaches to the scar and shows up white on scan
normally used for the assessment of regional scar formation and myocardial fibrosis
59
what is a CTCA
CT of coronary arteries
liquid containing iodine is injected into a vein
iodine increases density of blood in vessels allowing us to see inside and outside of vessels
beta-blockers to slow HR, CT can get imaging during diastole
60
what is a stress test
proves or excludes inducible ischaemia in myocardium
exercise or drugs are used if you are unable to exercise
Dobutamine is put in a vein and causes the heart to beat faster - mimics the effects of exercise on the heart
atropine and adenosine can also be used
61
contra-indications of an exercise stress test
unable to exercise
uncontrolled hypertension
unstable symptoms
62
pros and cons of a stress echo
```
pros:
cheap
very few side effects
safe
availability
ischemia and valve assessment
cons:
needs good acoustic window
operator dependent
expertise limited
```
63
nuclear cardiology
uses noninvasive techniques to assess myocardial blood flow, evaluate the pumping function of the heart as well as visualise the size and location of a heart attack
can also be a stress test
resolution not as good as MRI
coloured pictures produced
64
what is a coronary angiography
procedure that uses contrast dye, usually containing iodine, and x ray pictures to detect blockages in the coronary arteries that are caused by plaque buildup
65
what do the different colours in an xray mean
```
air = black
fat = grey
muscle = grey
bone = calcium = white
```
66
function of pleural cavity
fluid filled space that allows lungs to inflate and deflate against chest wall without friction
67
pectus excavatum
congenital deformity of the chest wall that causes several ribs and sternum to grow into the thoracic space
68
pectus carinatum
genetic disorder of the chest wall, making the chest stick out
happens because of an unusual growth of rib and sternum cartilage - sternum more pertuberant
69
role of diaphragm in breathing
diaphragm moving up and down is what causes lungs to inflate and deflate
it contracts causing itself to move down
lungs also move down due to them being in a confined space and this inflates the lungs - air drawn in
then diaphragm relaxes which pushes lungs up and air moves out - deflate
diaphragm separates the thorax from the abdomen
70
causes of diaphragm paralysis
```
Peripheral - phrenic nerve injury:
iatrogenic - surgery, anesthetic blocks
trauma
neuropathy
viral
central:
spinal cord injury
cord compression
central hypoventilation syndrome
tumors
```
71
which spinal nerves innervate the diaphram
C3, 4, 5
| phrenic nerve
72
causes of primary hypertension
```
smoking
obesity
diet - salt
lack of exercise
genetic
```
73
complications of chronic hypertension
```
leads to further cardiovascular disease:
atherosclerosis
stroke - BP higher in cerebral arteries - potential aneurysm
myocardial infarction
heart failure
renal failure
retinopathy
```
74
equation for BP
BP = TPR x CO
| where TPR = total peripheral resistance
75
lowering BP by drug action
block of sympathetic NS:
B1-blockers will reduce the effects on heart and will reduce renin release from the kidney
a1-blockers will reduce effects on blood vessels
kidney:
diuretics will reduce blood volume
hormones:
ACE inhibitors and angiotensin receptor blockers will inhibit the renin-angiotensin-aldosterone system
Ca+ channel blockers will cause vasodilation of peripheral resistance arterioles
76
what are Beta-adrenoceptor blockers and how do they reduce BP
competitive reversible antagonists that:
decrease BP via blockade of B1 sympathetic tone on the heart and reduction in renin release from the kidney
decrease HR and SV
decrease CO
77
Beta-adrenoceptor blocker examples
propanolol acts on B1 and B2
| atenolol is B1 selective
78
adverse effects of beta-adrenoceptor blockers
exacerbate asthma - block of B2 means absolute contraindication
intolerance to exercise
hypoglycaemia
vivid dreams
79
examples of alpha-adrenoceptor blockers
phentolamine blocks a1 and a2
| doxazosin and prazosin are a1 selective
80
what are alpha-adrenoceptor blockers and how do they reduce BP
competitive reversible antagonists
they decrease BP via a decrease in sympathetic tone in arterioles (a1)
decease in peripheral resistance
81
adverse effects of alpha-adrenoceptor blockers
postural hypotension due to loss of sympathetic venoconstriction
reflex tachycardia via baroreceptors
82
how do ACE inhibitors lower BP
reduced formation of the vasoconstrictor angiotensin II (decrease in peripheral resistance)
reduced blood volume (loss of angiotensin II-stimulated release of aldosterone, thus reduction of renal reabsorption of Na+ and water)
83
ACE inhibitor examples
captopril and enalapril
84
adverse effects of an ACE inhibitor
generally very well tolerated but:
sudden fall in BP on 1st dose
persistent irritant cough - due to reduced bradykinin (normally broken down by ACE), a peptide that activates sensory neurons in lung tissue
85
describe angiotensin II receptor blockers
two receptor subtypes: AT1 and AT2
AT1 receptor mediates vasoconstrictor and aldosterone-releasing actions of angiotensin
losartan and candesartan are AT1 blockers
86
how do diuretics lower BP
by reducing blood volume
mechanism is through reduced renal reabsorption of Na+ and water
additional vasodilator action may also contribute to decrease in peripheral resistance
87
adverse effect of diuretics
decrease in plasma K+
88
function of L-type voltage operated calcium channels
open upon membrane depolarisation
| calcium entry into cardiac and vascular smooth muscle
89
function of calcium channel blockers
reduce Ca2+ entry into vascular smooth muscle and cardiac muscle by blocking L-type voltage-operated calcium channels
90
mechanism of L-type channel block
open channel block - like a cork in a bottle - verapamil and diltiazem work this way
allosteric modulation - bind at allosteric site and reduce channel opening by conformation change - nifedipine works this way
91
how do calcium channel blockers reduce BP
```
reduce peripheral resistance (block of Ca2+ entry into vascular smooth muscle leads to vasodilation)
reduce CO (block of Ca2+ entry into cardiac muscle - HR and SV are both reduced)
```
92
difference between rate-limiting and non-rate limiting calcium channel modulators
non-rate limiting:
more effective vasodilators and more vascular-selective because the exhibit voltage dependent blockade - cardiac conducting cells are relatively hyperpolarised whereas vascular smooth muscle is relatively depolarised
rate-limiting:
have more marked effects directly on the cardiac conduction pathways and cardiac muscle
they slow HR and reduce conduction and contractility
93
adverse effects of L-type blockers
headache - dilation of cerebral blood vessels
constipation - relaxation of gastrointestinal smooth muscle
heart block - failure of cardiac myocytes to contract due to decrease Ca2+ concentration
cardiac failure
94
initial step in treating hypertension
person aged under 55 gets an ACE inhibitor or low cost angiotensin II receptor blocker
person aged over 55 or black person of African or Caribbean family origin of any age will get a calcium channel blocker
95
beginning of atherosclerosis
starts with insult to the vascular endothelium eg smoking, high shear stress, infection diabetes
increased adhesion and transmigration of leukocytes - create oxidant stress
increased permeability to lipids
generation of cytokines/oxidant stress
establishes a focus of inflammation
96
formation of a fatty streak
platelet adhesion
migration of smooth muscle cells - PDGF to form fibrous cap
uptake of modified LDLs - LOX-1
formation of lipid-laden foam cells (monocytes-macrophages)
release of MMPs by macrophages
compensatory vessel remodelling
97
advanced lesion in atherosclerosis
```
formation of fibrous cap-healing
foam cells burst/die and release lipid into necrotic core
necrotic core-lipids debris
further monocyte recruitment
oxidation of LDLs within plaque
```
98
unstable fibrous plaque
```
fibrous cap thins
thrombus formation
intraplaque haemorrhage
vessel occlusion
myocardial infarction
```
99
what makes a plaque vulnerable
larger lipid core
thinner fibrous cap
abundance of inflammatory cells
paucity of smooth muscle cells
100
what is cholesterol essential for
incorporating into cell membranes
maintaining membrane fluidity and permeability
production of steroids and fat-soluble vitamins
101
how does the liver effect cholesterol levels
liver monitors levels of cholesterol
regulates this through synthesis, absorption and bile secretion
drugs to treat hyperlipidaemia target this process in the liver/gut
102
lipoprotein examples
```
chylomicrons
VLDL
IDL
LDL
HDL
only HDL is good
```
103
chylomicrons
carry triglycerides from intestines to liver, muscle and adipose tissue
104
VLDL
carry newly synthesised TGs from liver to adipose tissue
105
IDL
an intermediate between VLDL and LDL
106
LDL
low density lipoprotein
major reservoir of cholesterol
taken up via LDL receptors by endocytosis
107
HDL
high density lipoprotein
adsorb cholesterol released by dying cells
also act as reverse transport to take cholesterol to liver
108
exogenous pathway of cholesterol transport
Dietary cholesterol and fatty acids are absorbed.
Triglycerides are formed in the intestinal cell from free fatty acids and glycerol and cholesterol is esterified.
Triglycerides and cholesterol combine to form chylomicrons.
Chylomicrons enter the circulation and travel to peripheral sites.
In peripheral tissues, free fatty acids are released from the chylomicrons to be used as energy, converted to triglyceride or stored in adipose.
Remnants are used in the formation of HDL.
109
how can obesity generate systemic inflammation
adipose tissue synthesises inflammatory cytokines
110
endogenous pathway of cholesterol transport
VLDL is formed in the liver from triglycerides and cholesterol esters.
These can be hydrolyzed by lipoprotein lipase to form IDL or VLDL remnants.
VLDL remnants are cleared from the circulation or incorporated into LDL.
LDL particles contain a core of cholesterol esters and a smaller amount of triglyceride.
LDL is internalized by hepatic and nonhepatic tissues.
In the liver, LDL is converted into bile acids and secreted into the intestines.
In non hepatic tissues, LDL is used in hormone production, cell membrane synthesis, or stored.
LDL is also taken up by macrophages and other cells which can lead to excess accumulation and the formation of foam cells which are important in plaque formation.
111
familial hypercholesterolaemia
a genetic disorder characterised by high cholesterol levels, specifically very high levels of low-density lipoprotein
most common mutations diminish the number of functional LDL receptors in the liver
112
signs of familial hypercholesterolaemia
xanthomas - fatty cholesterol-rich deposits on skin, usually around elbows, knees, buttocks and tendons
xanthelasmas - fatty deposits in the eyelids
arcus senilis - a white ring around the cornea
113
hyperlipoproteinaemia
high circulating levels of free and bound cholesterol and triglycerides
114
secondary causes of hyperlipoproteinaemia
diabetes mellitus, alcoholism, hypothyroidism, liver disease, drugs, diet
115
what are statins
HMGCoAR inhibitors
competitive inhibitors of rate limiting step in cholesterol biosynthesis
marked decrease in cholesterol levels may stimulate LDL receptor up-regulation
most effective at night when most cholesterol biosynthesis occurs
