Cardiovascular Flashcards
(192 cards)
1
Q
How are the AV valves attached to the heart?
A
Chordae tendinea attach valves to the papillary muscle
2
Q
How do semilunar valves close?
A
Pressure gradient caused by blood being pushed back following contraction
3
Q
Describe the steps of the cardiac cycle?
A
Atrial Systole begins
Atrial Systole ends, atrial diastole begins
Ventricular systole first phase (AV valves pushed closed by ventricular contraction- contraction not strong enough to open semilunar though)
(Isovolumetric contraction)
Ventricular systole second phase (pressure of ventricle exceeds arteries, causing semilunar valves open -> blood ejected)
Ventricular diastole early (Ventricles begin to relax, ventricular pressure drops, semilunar valves close due to backflow)
(Isovolumetric relaxation)
Ventricular diastole late (all chambers relaxed, ventricles fill passively)
4
Q
When does isovolumetric relaxation and contraction occur?
A
Contraction- between atrial systole ending/ diastole beginning and ventricular systole first phase starting
Relaxation- at the start of ventricular diastole
5
Q
When do the valves open and close?
A
Semilunars open- when ventricular pressure exceeds aortic pressure
Semilunars close- when aortic pressure exceeds ventricular pressure
AV valves open- when ventricular pressure has dropped and is equivalent to atrial pressure
AV valves close- when ventricles begin contraction
6
Q
What is inotropy and how does positive/negative inotropy impact stroke volume?
A
Contractile capability of the heart itself- how contractile the cells are
Positive- greater response of contraction (would increase stroke volume)
7
Q
What is the equation for cardiac output?
A
Stroke volume x Heart Rate
8
Q
What is the equation for blood pressure?
A
Cardiac Output x Peripheral Vascular Resistance
9
Q
What do cardiac contractile units look like?
A
Arranged linearly using intercalated discs
Contain a lot of mitochondria
Arranged in parallel with each other to enhance contraction efficiency
10
Q
What is the resting membrane potential of cardiac myocyte cells?
A
Around -80mV
11
Q
What is the general concentration of K, Ca and Na in cardiac cells?
A
High K intracellular concentration
Low intracellular Ca and Na
12
Q
What is the plateau phase and what causes it
A
Equal flow of ions in and out of cardiac cells
13
Q
What are the steps of cellular action potential of triggering contraction of cardiac myocyte cells?
A
Phase 0- Opening of voltage gated Na channels allowing for inward Na current. Rapid depolarization Phase 1 (notch)- Activation of outward K causing initial repolarization Phase 2 (plateau)- Balance of inward Ca and outward K flow- Plateau phase Phase 3- Repolarization phase, outward K predominates Phase 4- Resting action potential
14
Q
Do SA node cells ever reach resting membrane potential?
A
No, always active
Similar in AV node
15
Q
What is the back-up mechanism set up by the cells in the heart?
A
SA Node has constant slow depolarization with spontaneous depolarization.
AV node has this too but it is spontaneously active at a lower rate (intrinsically active in case something happens to the SA node)
Pirkinjes do this too
16
Q
How does calcium levels relate to action potential and contraction of the heart?
A
Action Potential depolarization causes increase in intracellular calcium transient, this allows for calcium binding to troponin, and binding of myosin to actin causing contraction
17
Q
Describe the movement of Calcium during the Ca induced Ca release.
A
L type calcium channels open (due to depolarization), allowing more calcium influx from T-tubule.
Ca reaches sarcoplasmic reticulum. Ryanodine Receptor on SR sense incoming of calcium through L-type calcium channel following action potential, and will then allow calcium release from SR.
18
Q
What is the L-type calcium channel?
A
Voltage gated calcium channel that allows inward flow of calcium once action potential initiates its opening
19
Q
What causes relaxation of cardiac cells (related to calcium) following contraction?
A
Pump on SR pumps calcium into SR to store
Calcium exchanger moves calcium out of cells
Lack of intracellular calcium causes blocking of actin from myosin via troponin re-binding
20
Q
What exchanger(s) moves calcium out of cardiac cells?
A
Ca-Na exchanger: Moves 3 Na into cell in exchange for 1 Ca out
ATP pumps: Used to move Ca out.
K-Na Pump: used to exchange 3 intracellular Na out, for 2 K, helping to control ion levels
21
Q
Where do the coronary arteries stem from?
A
Aortic sinus
22
Q
When does coronary flow occur?
A
During ventricular diastole
Aortic Valve shuts, pressure in ventricle falls, there is now a pressure gradient- higher pressure in aorta, and lower in ventricular muscle allowing for coronary flow (blood will flow backwards in aorta due to the higher aortic pressure and blood will flow down to coronary arteries)
23
Q
What structure makes up the inferior, superior, right, and left border of the heart?
A
Inferior-Right ventricle
Right- right atrium
Left- Left ventricular wall
Superior- great vessels, part of left and right atrium
24
Q
What is occurring within the heart between the lub-dub?
A
Ventricular systole is beginning and ending during this period
Ventricular pressure is high, aortic pressure is high
25
What do the lub-dub noises during auscultation represent?
Lub- Closure of AV valves
| Dub- Closure of semilunar valves
26
When does the radial pulse occur while auscultation?
During the 1st and 2nd lub-dub
27
Where would you listen for the aortic valve?
2nd-3rd right intercostal space
28
Where would you listen for the pulmonic valve?
2nd-3rd left intercostal space, adjacent to the sternum
29
Where would you listen for the mitral valve?
Midclavicular line at the 4-5th intercostal space on left side.
30
Where would you listen for the tricuspid valve?
Left sternal border towards the apical level of the heart (4th 5th intercostal space)
31
What does Jugular Venous Pressure determine?
Atrial pressure
32
What cardiac diseases impact the mechanics of the heart?
Cardiomyopathy
| Valvular Disease
33
What cardiac diseases impact the electricity of the heart?
Arrhythmias
| Conduction System Disease
34
What cardiac diseases impact the blood supply of the heart?
Coronary Heart Disease
35
When examining a patient for cardiovascular check-ups, what can be observed in the hand/feet and what could this indicate?
Nail Beds: Splinter Haemorrhages (infective endocarditis)
Osler nodes: Found typically on toes and fingers (subacute endocarditis)
Janeway Lesions: Red, painless lesions on palms/soles caused by septic microemboli (could indicate acute endocarditis)
Peripheral Cyanosis: COPD, heart failure, abnormal haemoglobin, local vasoconstriction (cold environment)
Clubbing: Loss of nail bed angle (lung cancer, pulmonary fibrosis, atrial myxoma (non-cancerous tumour), congenital cyanotic heart disease)
Tendon Xanthomas: subcutaneous nodules (hyperlipidaemia/cholesterolemia)
Pallor: anaemia, low cardiac output states, peripheral vasoconstriction during shock
36
What are signs of endocarditis?
Splinter Haemorrhages
Osler nodes
Janeway Lesions
37
When checking radial pulse, what are you looking for, and what can variations of these indicate?
Rate
Rhythm: regular, regularly irregular (i.e. regular dropped beat in 2nd degree blockage), irregularly irregular (atrial fibrillation, ectopic beats)
Volume: weak (shock), strong (anaemia, fever, hyperthyroidism)
Character: Regular rise with quick collapse (aortic regurgitation), slow to rise (aortic stenosis)
38
When examining the heart, what can evaluation of the eyes indicate?
Conjunctival Pallor: Anaemia
Xanthelasma: Hypercholesterolemia (cholesterol deposit under skin around the eyes - typically congenital)
Corneal Arcus: Hypercholesterolemia / hypertriglyceridemia (milky-blue deposit around cornea)
39
When examining the heart, what can evaluation of the mouth indicate?
High arches palate: May indicate Marfan's Syndrome
Central cyanosis: blue-ish tongue/ mucous membranes due to hypoxaemia (pulmonary embolism, congenital cyanotic heart disease)
40
What can a visual presence of jugular ventricular pressure pulse indicate, and how does it look??
Can indicate heart failure, valvular disease (tricuspid regurgitation (often have very noticeable pulse), heart block (see cannon waves)
Double pulsation, not palpable, changes with respiration/position changes, pulse can be stopped with pressure
41
What waves are observed when examining a visible JVP pulse?
A and V
42
Where is the JVP pulsation observed (if visible)?
Between two head of sternocleidomastoid, immediately superior to clavicle
43
What is phenylephrine and what does it do?
Agonist of alpha 1 receptors on vessels driving vasoconstriction
This is used as a nasal decongestant (as constriction to nasal cavity reduces congestion)
44
What role does oestrogen play in vessel constriction?
It is a vasodilator and hypotensive.
| This relates to why female BP rises following menopause
45
Do systolic pressure differ in men and women?
Yes, women's are lower up until about 65 when it slowly overtakes men
46
What is normal structure of a vessel and what is found in each layer? Start most superficial.
Perivascular fat
Tunica adventitia- nerves, macrophages, fibroblasts , stem cells, elastin, collagen.
Media- smooth muscle cells
Intima- Endothelial cells
47
How do endothelial cells within the tunica intima communicate with smooth muscles cells within the tunica media?
Via small whole in the internal elastic lamina
This layer separates the intima and media
The wholes can shrink with hypertension
48
What happens to vessel walls with hypertension and why?
Vessel increases in length because smooth muscle cells are arranged in helical fashion, perpendicular to axis of flow (like spring)
Vascular remodelling-- increased lumen to media ratio, media gets thicker, lumen gets thinner (this increases resistance)
49
What impacts flow the most, radius or length?
Radius have largest impact on flow
50
What is inward and outward vessel remodelling?
Inward- narrowing of vessel lumen
| Outward- widening of vessel
51
How can vessel wall change in terms of thickness?
Hypertrophic- vessel gets thicker
Eutrophic- no change in vessel thickness
Hypotrophic- thinning of vessel wall
52
Why is patient compliance so important in terms of hypertension?
Drugs will reduce pressure for patients, and they will start to feel normal and not want to continue meds.
However, vessels have undergone remodelling and will go back to hypertensive state.
53
What role does angiotensin 2 play in terms of tunica media?
Vasoconstrictor
Increased in those with hypertension
Growth factor that causes muscle cells to proliferate and migrate
54
What drugs are best in terms of reversing remodelling changes caused by hypertension?
ACE inhibitors like perindopril
55
Why does remodelling of vessels occur due to hypertension?
When you have high BP your vessels remodel to accommodate the increased pressure and protect downstream organs
56
What do sympathetic nerves release from their axons and what does it act on?
Noradrenaline neurotransmitter acts on alpha and beta receptors
57
What is a baroreceptor and where are they?
Found at carotid sinus and aortic arch
| They are sensors that detect stretch in vessels and signal to brain the amount of pressure present in the vessel
58
How can you reduce blood pressure using the sympathetic nervous system?
Reduce heart rate
| Reduce resistance via vascular tone using reduced sympathetic input/drive
59
Where do the majority of nerves act within vessels?
Tunica adventitia border with media
60
What neurotransmitters act on smooth muscle cells of vessels, and what are their receptors?
Noradrenaline- alpha 1 adrenergic (GCPR)
Neuropeptide Y- Y receptors
ATP- Purinergic Receptor- P2x (ligand-gated ion channel)
Called sympathetic triad
61
What is the name for the lattice network innervating the smooth muscle cells of vessels?
```
Sympathetic triad (NA, NPY, ATP neurotransmitters)
-allows for fine regulation of contraction of smooth muscle cells.
```
62
What are the nerve-mediated response components to vessel contraction?
Purinergic - by ATP neurotransmitter
| Adrenergic- Noradrenaline
63
How can you boost contraction in a vessel in relation to the sympathetic triad?
A little release of neuropeptide Y will boos the action of ATP and Noradrenaline neurotransmitters on the vessel smooth muscle cells.
64
How does neuropeptide uptake occur within varicosities?
The uptake of neuropeptides is determined by the neuron/recipient at that given synaptic bouton.
Peptide will cycle round the varicosities
65
How does noradrenaline release and uptake occur?
Dopamine is taken up into vesicle where dopamine beta hydroxylase converts it to noradrenaline.
NA is released by vesicle and will stimulate a1 receptors of recipient nerve/cell.
NA also binds a2 receptors on the axon releasing it, causing negative feedback loop (pre-junctional autoinhibition)
66
What is the U1 uptake mechanism and what is its purpose?
Uptake 1 regulates concentration on Noradrenaline in synaptic cleft, and will uptake NA back into releasing nerve if there is too much.
67
Can fat impact contraction of a vessel?
Yes, but it is not fully understood how
68
How do sensory nerves relate to smooth muscle cell innervation in vessels?
Perhaps sensory nerves have some transmitters impacting surrounding fat and smooth muscle cells
69
What happens prior to the P wave of an ECG?
Impulse formation in SA node- does not appear on ECG
70
What happens at the P wave on an ECG?
Depolarization of atrial muscle
71
What happens at the delay point on an ECG?
This is priming event to fill the ventricles.
72
What happens at just prior to the QRS phase on an ECG in terms of action potentials?
AV node signal conducts down bundle of his to left and right branches along septum.
Conduction through purkinje fibres, and first deflections of QRS are seen.
73
What happens at the QRS phase on an ECG?
Ventricular depolarization and atrial repolarization
74
What happens at the ST segment on an ECG?
Inward calcium and outward K currents are balanced and produce plateau in action potential, reflected in ECG following QRS phase.
75
What happens at the T wave on an ECG?
Ventricular repolarization
| Much slower than QRS
76
What is an ECG lead?
An electrical vector
| Its a view point of the heart- not the wires connecting to the patient
77
What are the types of vector leads seen on ECG Leads?
Unipolar- Measure potential variation at a single point
(Augmented Limb Leads (aVR, aVL, aVF), Chest Leads (V1-V6))
Bipolar- Measure potential difference between two points
(limb leads 1 (Right Arm-Left Arm), 2 (RA-LLeg), 3 (LA-LL))
78
What leads allow for an inferior view of the hearts electrical activity?
2, 3, aVF
79
What leads allow for an anterior view of the hearts electrical activity?
V1, V2, V3, V4
80
What leads allow for an lateral view of the hearts electrical activity?
1, aVL, V5, V6
81
How does polarity of signals impact the waveforms?
Movement away from an electrode would result in a negative wave, towards creates positive
Movement moving across electrode (i.e. perpendicular to towards/away) would result in a signal curved wave
82
What is the QRS axis, what is normal?
Way to quantify overall depolarization of heart and if results from an ECG are normal.
Normal= -30 to +90.
83
What are the first things that should be done when checking an ECG?
Ask for clinical context
Check dates and details
Assess technical quality
Identify P/QRS/T waves with rhythm strips (lead 2 or V1)
Using those complexes, measure heart rate, axis, intervals
Then look at morphology
Don't rely on automatic interpretations
84
How do you determine HR on and ECG?
Count large squares between QRS complexes and divide into 300
85
What are normal time frames for the PR Interval, QRS wave and QT interval?
PR- <1 large square (<200ms)
QRS- <3 small squares (120ms)
QT- <11 small squares (440ms)
86
How do you determine if there is deviation on the QRS axis?
Lead 1 and 2 should be most positive (found by looking at positivity of the QRS waves in these leads and comparing it to any negative polarity).
If they are more negative, or other leads show stronger positivity, the axis is "spun" towards these particular leads. This can help you identify if different areas of the heart are/aren't being depolarized as they should be.
87
What are normal patterns to keep in mind when evaluating an ECG?
P wave is upright for inferior leads (L2, L3, aVF)
ST segment should be flat
T wave has the same polarity as QRS
88
How are P waves described?
Positive
Negative (inverted)
Biphapasic
89
What may a non-flat ST segment indicate?
Depressed may indicate blood flow during plateau phase typically caused by ischemia
90
How are QRS waves described?
```
First deflection negative = Q wave
Positive deflection= R wave
Any neg deflection after R = S wave
Any further pos deflection = R'
Capital letter= dominant wave
Small letter= non-dominant wave
```
91
How are T waves described?
Upright
Inverted
Flat
Also concordant (same) or discordant vs QRS
92
How is a JVP measurement taken?
Lay patient flat with head 45 degree towards left.
Begin to ascend patient until jugular pulse begins to lessen, then take a measurement from the manubriosternal junction with the ruler held upright.
Take measure of JVPs maximum height, over 4cm is abnormal.
93
Why is coronary flow diastolic?
During systole, the heart it too constricted to allow blood through, but when it relaxes the blood can pass
94
In reference to metabolism, what happens in disease when the heart rate is increased?
Aerobic respiration switches to anaerobic metabolism which brings on angina
95
What releases ANP and what does it do?
Atrial Natriuretic Peptide
Released by posterior muscle of the heart (receptors here sense increases in volume, and create/secret ANP i response)
It dilates arterioles in kidneys
Essentially works in opposite manner to aldosterone by suppressing reabsorption of Na in collecting ducts, aiding in water loss to reduce BP
96
In the cardiac system (heart and vessels) is hypertrophy or hyperplasia more common?
Hyperplasia is more common in vessel walls with plaques
| The heart tends to lean towards hypertrophy
97
How is cardiac output influenced by the autonomic system?
SA node has input from symp and parasymp (vagus nerve- drops heart rate)
98
What are the different grades of blood pressure (including normal)
```
optimal- <120/80
Normal- <130/85
High normal- 130-139/ 85-89
Grade 1- 140-159/ 90-99
2- 160-179/ 100-109
3- >180 / >110
Isolated systolic:
grade 1- 140-159/ 80
grade 2- >160/ 80
```
99
What are primary causes of hypertension?
```
Smoking
Obesity
diet (salt)
exercise (lack)
genetics
```
100
What is secondary hypertension?
Caused by another morbidity (renal hypertension or pheochromocytoma)
Treated by treating cause
Accounts for 10% of hypertension cases
101
What implications does hypertension have?
```
Atherosclerosis
Stoke
MI (due to thrombis)
Heart failure
Renal failure
Retinopathy
```
102
What clinical benefits are seen in treating high BP?
40% reduction of stroke
25% reduction in MI
>50% reduction in heart failure
103
How is BP calculated?
BP = total peripheral resistance x cardiac output
Cardiac output= heart rate x stroke volume
104
What leads to isolated systolic pressures?
Calcification of vessels
105
What effects do beta blockers have?
Competitive reversible antagonist
Reduce effects of sympathetic nervous system on heart tone
Reduce renin release from kidneys
Both result in:
Reduced heart rate and stroke volume (on cardiac muscle) ->
Reduced cardiac output
Speeds up relaxation of heart
106
What systems and/or organs can we impact in order to lower BP via drug action (touch on how)?
Block sympathetic nervous system (beta 1 and alpha 1)
Kidney (Diuretics)
Hormones (RAAS pathway- ACE and angio receptor blockers)
Vasodilation or peripheral arterioles (Ca channel blockers)
107
What are two examples of beta blockers?
Propranolol (beta1/2)
Atenolol (Beta 1 selective)
WHY ARE WE MOVING AWAY FROM BETA BLOCKERS- there's always a bit of cross-over
108
What are adverse effects of beta blockers?
Activating beta 2 receptors in lungs- big problem for asthmatics
Intolerance to exercise (less able to raise heart rate and forced contraction)
Hypoglycaemia (effects on pancreas)
Vivid dreams (particularly hydrophilic drugs)
109
What are examples of alpha blockers?
Phentalamine (alpha 1 and 2)
| Doxazosin, prazosin (alpa 1)
110
What impact do alpha blockers have on the body?
Competitive reversible antagonist
Reduce BP via reduction in sympathetic tone in arterioles
Reduce peripheral resistance
111
Besides inducing peripheral vasodilation, what can alpha receptor blockers also be used for?
Alpha 1 blockers are also used in Benign Prostatic Hyperplasia as it blocks alpha receptors of internal sphincter, helping to reduce constriction and allow for urination
112
What are ACE inhibitors?
Inhibit angiotensin converting enzyme on vascular endothelial surface
preventing conversion of angiotensin 1-> 2
113
What physiological changes do ACE inhibitors cause?
Reduced blood volume (via reduction in aldosterone which increase Na reabsorption)
Reduces formation of vasoconstricting-angiotensin 2 (reduction in peripheral resistance)
114
What are adverse impacts of ACE inhibitors?
Sudden fall in BP on first dose
| Persistent irritant cough (reduced breakdown bradykinin, which activates sensory nerves in lung tissue)
115
What are adverse impacts of ACE inhibitors?
Sudden fall in BP on first dose
| Persistent irritant cough (reduced breakdown bradykinin, which activates sensory nerves in lung tissue)
116
What are angiotensin 2 receptors blockers and the main subtypes?
Blocks Angiotensin 2 receptors
Two receptors subtypes AT1 and 2
AT1 mediates vasoconstriction, aldosterone synthesis/secretion, vasopressin (ADH) secretion- thus we want to bind/block this receptor to allow for reduced BP
AT2 may play role in causing vasodilation, thus only want to block AT1
117
What are diuretics and an example?
Bendroflumethiazide
Lower BP by reducing volume via increased excretion of Na and therefore water
Additional vasodilator action may also reduce peripheral resistance?
118
What is the main side effect of diuretics?
Reduced plasma K
| Not good as if you lower K too much it can cause problems with the heart (bradycardia)
119
What are calcium channel blockers and an example?
Verapamil, diltiazem, nifedipine
Block L-type voltage channels (present in heart and muscles- these channels stay open a long time to allow calcium entry into cardiac and vascular smoother muscle)
Reduced Ca entry into vascular smooth muscle reduced vascular resistance
120
What is the mechanism of action of L-type calcium blockers
Open Channel Block:
When channel opens, the drug goes into the channel and blocks the pore, which doesn't allow calcium through the pore.
Allosteric modulation:
Bind on different part of receptor to change morphology of the receptor, disallowing calcium to move through
121
What are differences in rate limitations of calcium blockers?
Some are non-rate limiting:
They dont change the heart rate much, primarily impact vasodilation
Rate-limiting: Act more directly on the hearts conduction pathway, working to slow and reduce conduction (verapramil, dilitazem- they favour hyperpolarized membranes)
122
What are some adverse reactions to L-type calcium blockers?
Headache (dilation of cerebral blood vessels)
| Constipation (relaxation of gastro smooth muscle)
123
How would prescription of anti-hypertensives be done in people under 55?
Step 1: Ace inhibitors or low-cost angiotensin 2 blocker
Step 2: Combine with calcium channel blocker
Step 3: Add thiazide-like diuretic
Step 4: Consider more diuretics and/or expert advice
124
How would prescription of anti-hypertensives be done in people over 55, or a person of African/ Caribbean family origin of any age?
Step 1: calcium channel blockers (why? ACE are less effective in people over 55 or of African descent)
Step 2: Combine with Angiotensin 2 blocker or ACE-inhibitor
Step 3: Add thiazide-like diuretic
Step 4: Consider more diuretics and/or expert advice
125
Where do atherosclerotic plaques build?
In the tunica intima
| fatty streaks begin to appear in coronary arteries 5-10years later than the aortic
126
Is there a relationship between fatty streaks and atherosclerosis?
Fatty streaks are the first visible sign of atherosclerotic plaque formation
127
What is vessel remodelling?
Changes in size of vessels to allow for changes in lumen due to things like development of atherosclerotic plaques
128
What causes fatty streak formation?
Insult to endothelium (smoking, high shear stress, infection, diabetes, high turbulent flow at certain points)
Increased adhesion and transmigration of leukocytes (once into the intima layer beneath endothelial cells create oxidant stress)
Increased permeability to lipids
Generation of cytokines/ oxidant stress
Establishes a focus of inflammation
129
Why is increased oxidative stress in terms of atherosclerotic plaques development a bad thing?
Oxidative stress is a normal response to infection, but here it can damage the structures in the vessels via oxidation of proteins, lipids, and DNA, causing cell damage and more recruitment of inflammatory mediators.
Oxidative stress also causes increases in superoxide, which decreases availability of nitric oxide reducing smooth muscle relaxation
130
What is the formation of atherosclerotic lesion?
Formation of lipid-laden foam cells (monocytes/macrophages)
Formation of fibrous cap (which locks lipid build up in place preventing embolism)
Release of MMPs by macrophages
Compensatory vessel remodelling
131
What happens in unstable plaques?
Plaque/thrombus is more likely to ruptures, (intraplaque haemorrhage can also occur- in well developed plaques can sometimes have their own blood supplies, which increase plaque size),
If rupture occurs, there's increased likelihood of activation of the clotting cascade, a thrombus will form, and can lead to MI
132
What happens in unstable plaques?
If plaque/thrombus ruptures, (intraplaque haemorrhage can also occur- in well developed plaques can sometimes have their own blood supplies, which increase plaque size),
There is activation of the clotting cascade, a thrombus will form, and can lead to MI
133
What are vulnerable plaques?
Plaques with thinner fibrous caps, larger lipid cores, abundance of inflammatory cells (increasing oxidative stress which can damage the plaque), paucity of smooth muscle cells (if plaque binds on to it).
134
What is cholesterol essential for?
Incorporating into cell membrane
maintaining membrane fluidity/permeability
production of steroids/fat-soluble vitamins
135
How is the liver important in relation to cholesterol?
Monitors cholesterol levels,
regulates it through synthesis, absorption, bile excretion,
drugs used to treat hyperlipidaemia target this process in the liver/gut
136
How is cholesterol transported?
Formed into complex with:
Lipids (cholesterol esters with hydrophilic head, triglycerides, free fatty-acids)
Apoproteins
137
What are different Lipoproteins?
Chylomicrons - carry Triglycerides to liver, muscle, adipose
VLDL- carry newly synthesized TriG from liver to adipose
IDL- intermediate between VLDL and LDL
LDL- major reservoirs for cholesterol, taken up via LDL receptors by endocytosis (to help synthesize membranes)
HDL- absorb cholesterol released by dying cells , acts as reverse transporter to take cholesterol to liver
138
What is the exogenous pathway of cholesterol absorption and movement?
1. Chylomicrons take absorbed lipids
2. In capillaries, lipoprotein lipase enzyme attacks lipids and lipoproteins to take off 3 fatty acids so they can be stored in adipose
3. Left with chylomicron remnant which expresses APOE which interacts with remnant receptors and takes chylomicron into the liver
139
What is the endogenous pathway for lipoprotein metabolism?
Free fatty acids stored in liver can be formed into VLDL, which circulates and is broken down (lipase) into LDL and IDL
IDL can be acted on by hepatic lipase to form LDL (remaining IDL can be up-taken by liver)
LDL is then transported to muscle, by extrahepatic cells, or scavenger cells, or received by LDL receptors in liver again.
140
What happens in familial hypercholesterolaemia?
Cant take LDL back up into the liver,
| So LDL can still be produced, but there are low LDL receptors meaning it isn't taken back up
141
What is a sign of familial hyperchol?
Xanthelasma- fatty cholesterol rich deposits around eye
Xanthomas - deposits of cholesterol in skin
Angina
Calf cramps
142
What are statins, and what is their mechanism of action?
Inhibit β-Hydroxy β-methylglutaryl-CoA reductase (HMG-CoA Reductase) in liver (this prevents formation of cholesterol precursors)
Competitively inhibit rate-limiting step in cholesterol biosynthesis
Reduce synthesis of LDL by liver, this level will fall in liver and increase LDL receptors in order to take LDL up out of plasma.
Most effective at night as this is when most biosynthesis occurs
143
Are statins effective in people with familial hypercholesterolaemia?
In most severe cases, likely not effective, but recessive inheritance it may help
144
What are elastic arteries?
Conducting arteries- very thick tunica media rich in elastin sheets separated by collagen fiber and smooth muscle cells. Contain vasa vasorum for blood supply.
Include aorta, pulmonary, common carotid, brachiocephalic, subclavian, and iliac arteries.
145
What are muscular arteries?
Distributing arteries- thick tunica media with concentric smooth muscle cell layers. Media is bordered by internal and external elastin layers
Most abundant artery type in body
Elastin aids in regulating flow to tissue/organs
146
How do skeletal muscle metabolites impact vasoconstriction/dilation of arterioles?
The following events within smooth muscle of vessels cause arteriole vasodilation
- Partial pressure of oxygen (PO2) decreases
- Partial pressure of carbon dioxide (PCO2) increases
- Production of H+ ions increases (pH decreases)
- Temperature increases
147
What layers make up the capillary wall?
Tunica intima consisting of 1 layer of endothelial cells
No tunica media
thin or absent tunica adventitia
148
How is blood entry into capillaries regulated?
Precapillary sphincters and arterioles.
149
At rest, how much of the total blood volume in the systemic circulation is found in the veins?
64%
150
What aspect of the nervous system regulates veins, and what implications can its innervation have?
Sympathetic nervous system
| Stimulation will cause venoconstriction which will aid in returning blood to the heart
151
What layers make up a vein?
Thin tunic intima and media
Thick tunica adventitia
May contain valves (venules do not contain valves)
152
What is the vessel diameter of arteries, veins, and capillaries?
Arteries: 4-25 mm
Capillaries: 0.5 µm
Veins: 4-30mm
153
Describe the wall composition of arteries, capillaries and veins in terms of fibrous, muscular, and/or elastic.
Arteries: Elastic and muscular
Capillaries: Only endothelium
Veins: Muscular and fibrous
154
What causes dizziness when standing up from a seated position, and how is this corrected?
Blood pools to lower limbs, reducing return of blood to heart -> decreased stroke volume/ cardiac output -> fall in systolic bp -> baroreceptor reflex -> sympathetic input -> increased heart rate/ contractility
155
What is orthostatic or postural hypotension?
Slow cardiovascular response to postural changes due to loss/reduction in peripheral autonomic (sympathetic) function
Decrease of 20mmHg in systolic or 10mmHg diastolic within 3 minutes of standing are classified as orthostatic/ having postural hypotension
156
What do you feel when you feel a pulse?
The propagating pressure wave through the artery
157
What is central venous pressure and how is it determined?
The pressure within the vena cavae. It provides an estimate of the pressure within the right atrium of the heart.
Measurement of CVP requires an invasive procedure using catheter.
158
What is jugular venous pressure and how is it determined?
Alternative (less invasive) way to estimate the Cardiac Venous Pressure.
Measure elevation distance of JVP from sternal angle while patient is at 45 degree angle.
159
What can Central Venous Pressure elevation indicate?
Right-sided heart failure
| Hypervolemia of blood/ECM
160
What blood vessels are responsible for regulating blood flow?
Arterioles
161
Where is the largest drop in pressure seen within circulation?
In arteriole by about 55%
| Arterioles also provide the largest resistance to flow
162
What are Korotkoff sounds?
Sounds generated by turbulent blood flow that we observe while measuring blood pressure with a sphygmomanometer
163
When checking blood pressure, what sounds indicate systolic and diastolic?
Systolic- first turbulent (korotkoff) sounds heard as sphygmomanometer pressure slowly declines
Diastolic- Point where muffling is heard (or disappearance of sound)
164
What is cardiac output and how is it calculated?
Volume of fluid leaving the heart per minute
| Stroke Volume x Heart Rate
165
What is series vs parallel resistance?
Series would be artery -> arteriole -> capillary
| Parallel would be the combination of vessels and the different routes blood can take
166
How can you calculate mean arterial blood pressure?
Cardiac Output X Total Peripheral Resistance
| TPR = change is pressure gradient/ flow rate
167
What is Starling's Law of the Heart?
Up to a point, the heart will pump out whatever volume it receives
168
What is the calculation for mean arterial blood pressure and what is the average range?
DP + (1/3 X Pulse Pressure)
Normal range is 70-105mmHg
PP= SP-DP
169
What are the primary mechanisms of autoregulation in relation to endothelial, metabolic, and myogenic vessel diameter?
Endothelial: the endothelium is able to produce specific vasodilating factors. These are prostacyclin and the gas, nitric oxide (NO).
Metabolic: when blood flow is reduced, the resultant hypoxia causes localized release of vasodilating factors from tissue surrounding blood vessels.
Myogenic: blood vessels that contain smooth muscle are able to alter their diameter in response to stretch or compression of the blood vessel
170
What is compliance in relation to vessels?
How much a blood vessel's volume changes (ΔV) with a given pressure change (ΔP) is the compliance of the vessel (ΔV/ΔP).
I.e. A blood vessel that easily expands at low pressure is said to have a high compliance.
171
What cells within the kidney are responsible for sensing changes in pressure? Describe both and their role related to bp.
Juxtaglomerular Cells- Modified smooth muscle cells in walls of kidney arterioles that release renin in response to decreases in local blood pressure, sympathetic stimulation, and prostaglandin E2 (PGE2) secretion by macula densa
Macula Densa Cells- Detect changes in NaCl within distal convoluted tubule, when bp drops, glomerular filtration drops, and NaCl delivery to here is reduced which stimulates MD release of PGE2 triggering renin release from JG cells
172
What role does angiotensin 2 play in relation to the body?
Causes:
ADH (produced by hypothalamus) release from posterior pituitary gland
Resets baroreceptor reflex (preventing input the minute bp begins to rise) by acting on hypothalamic receptors
Increases aldosterone release by adrenal glands
Increases peripheral resistance via arteriole vasoconstriction
173
What is Atrial Natriuretic Peptide, what does it do, and what signals its release?
ANP reduces blood pressure
Baroreceptor stretch signals its release from atrial cardiac muscles
ANP effects:
Inhibit renin release from kidneys (leading to vasodilation)
Increases glomerular filtration via afferent dilation and efferent constriction,
Inhibits Na reabsorption at collecting ducts (increasing fluid excretion)
Inhibits aldosterone release from adrenal glands (increasing Na excretion)
174
Does short-term regulation of BP involve nerves and hormones?
Involves nerves but not hormones
| Long-term involves both
175
When evaluating the time taken to act (i.e. minutes vs hours), where do the following fall: ADH, aldosterone, angiotensin 2, ANP, and renin?
Minutes: ADH, ANP, renin, angiotensin II
Hours: Aldosterone
Aldosterone is a steroid hormone and initiates transcription of proteins which takes hours, as opposed to the others (all peptides) which bind extracellular and initiate second messengers
176
What is tampenade?
Compression of the heart due to excess fluid and/or fibrous pericardium
177
What is a pericardiocentesis?
Remove part of fluid within the pericardial sack
178
What impressions aid in identifying the left/right lung?
Left: Aortic arch, descending thoracic artery
Right: Superior vena cava and Azygous veins
179
What is stenosis and what can it cause in terms of pathology?
Stiffening of the valves.
| Can lead to ventricular hypertrophy as it is harder to pump blood
180
How is the superior vena cava formed?
Left and right brachiocephalic veins, each have contributions from internal jugular, and subclavian
181
What is the azygous vein and why is this system important?
Drains directly into superior vena cava from the posterior thoracic wall and upper abdomen.
Major contribution to collateral circulation in draining thoracic and abdomen regions
182
What structures are found in the right atrium?
Openings of coronary sinus, superior and inferior vena cavas
Fossa Ovalis- in growing foetus, foramen ovale connects right and left atrium, this closes and leaves remnant.
Crista terminalis- boundary between the rough (pectinate muscles) and smooth muscle (sinus venarum) in atrium
Sinus venarum also helps forms SA node and coronary sinus
183
What impact can patent foramen ovale have?
Small strokes- clot formed in right ventricle and moves directly into systemic circulation
Migraines (due to lack of lung filtration of toxins)
184
Describe foetal circulation from exchange to the heart.
Gas exchange occurs at placenta
Oxygenated blood enters circulation through umbilical vein
Blood can either move into the liver, or can move through ductus venosus passage into the inferior vena cava
Vena cava -> right atrium
Right atrium -> foramen ovale -> left atrium
Left atrium -> left ventricle -> systemic circulation
Some blood in right atrium will still move to right ventricle to supply the lungs. This blood returns via pulmonary veins, and will move directly into the aorta via ductus arteriosus.
185
Why is blood oxygenation lower in the foetal descending aorta?
The ductus arteriosus conjoins with the aortic arch, returning partially deoxygenated blood from pulmonary circulation (which was used to supply the lungs) into oxygenated aortic blood. This reduces oxygenation from this point down.
186
What are auto-rhythmic cells?
Cells that have capacity to excite and cause contraction.
| 2 groups, SA node and AV node. SA is dominant
187
What structures are found in the right ventricle?
Tricuspid valve
Chordae tendineae- attach cusps of tricuspid valve to papillary muscles
Papillary muscles- attachment of chordae tendineae
Pulmonary valve
Trabeculae carneae- muscular ridges in wall
188
What structures are found in the left ventricle?
```
Mitral valve
Chordae tendineae
Papillary Muscles
Aortic valve
Trabeculae carneae
```
189
What structures are found in the posterior mediastinum?
Oesophagus
Descending thoracic aorta
Azygous veins (and hemi-azygous)
Thoracic duct (between conjoining of left internal jugular and subclavian- Left Venous Angle)
190
Where are bronchopulmonary lymph nodes found in the thorax?
Surrounding the principle bronchi
191
What are the chordae tendinae?
Cord-like tendons that connect the papillary muscles to the valves
192
Which vein arches over the hilum of the right lung to drain into the superior vena cava?
Azygous
