1
Q
Where are baroreceptors located?
A
- Pre-glomerular arterioles
- Responsible for releasing Renin
- Production of AngII
- Carotid sinus
- Thin walled
- Very compliant—so very sensitive
- can repsond within 1 cardiac cycle
- Highly innervated
- Internal carotid artery
- Na2+ same as a stretch receptor is also in the kidney in the distal nephron
- That is the stretch receptor in the carotid sinus
- Aortic arch
2
Q
What part of the brainstem contains the cardiovascular control centre?
A
- The medulla
- Pressure and depressor
- For high and low pressure
- Operates via sympathetic and parasympathetic nerves
3
Q
Activation of the sympathetic nervous system results in?
A
- Increased HR
- Decreases atrioventricular conduction time
- The AV conduction is between the AV and ventricle—so faster conduction.
- Increase cardiac contractility
- Greater stroke volume
- Ca2+ concentration within the cells is increased when you activate the sympathetic nervous system so you increase the activation of the actin/myosin
- Increase total peripheral resistance
- Keep blood in arteries
- Increase venous tone
- Push on the veins and deliver more blood to the heart
4
Q
What happens when we activate the parasympathetic nervous system?
A
- Reduced heart rate
- Increase atrioventricular conduction time
- Doesn’t reduce total peripheral resistance
- There are some areas where there is vasodilation due to the parasympathetic nervous system but doesn’t really make a difference
5
Q
Summary of the autonomic nervosu system effects on controlling blood pressure
A
6
Q
What is the function of chemoreceptors?
A
- The baroreflex stops firing at 60mmHg so we use the chemical detection system
- Respond to very low O2
- Carotid and aortic bodies outside arteries
- Look like peas with nerves around them
- Are stimulated at very low MAP
- Low flow
- Low O2, high CO2, low pH
7
Q
What does high blood pressure predispose us to?
A
- Coronary disease
- Stroke
- Cardiac hypertrophy
- Heart failure
- Kidney failure
8
Q
What happens to the blood pressure in the ageing adult?
A
- Systolic BPO rises until 60 years of age
- Systolic rises after 60 years of age
- Diastolic BP rises until 60 years of age
- Diastolic pressure usually remains the same or goes down after 60
- Because we get increased pulse pressure
- Stiffening of the arteries—less compliance
- So blood vessels can no longer accommodate lower volumes of blood and blood pressure falls
- i.e. blood vessels no longer constrict as much (due to low compliance) when there is less
- So blood vessels can no longer accommodate lower volumes of blood and blood pressure falls
9
Q
What is the diurnal variation in blood pressure?
A
- Blood pressure is lower night (20mmHg)
- sympathetic action decreases-so Renin AngII system more active at night
- during the day everyday activitues increases sympathetic activity
- less variability at night
10
Q
Is blood pressure higher in summer?
A
- No it is lower
- due to the vasodilation and sweating (lose fluid-CO output drops)
*
11
Q
What is the populaiton paradox?
A
- The greatest number of deaths occur in individuals in the middle region of the blood pressure normal distribution
12
Q
The breast is from?
A
- the 2nd rib to the 6th rib
13
Q
How many ribs do we have?
A
- 12
14
Q
What is the sternum comprised of?
A
- The monubrium, sternum and xyphoid process
15
Q
Ribs artciculate with the costal cartilages and then those costal cartilages articulate?
A
- Upper 1-7 articulate with the sternal complex directly
- Costal cartilages 8,9 and 10 turn up and articulate with the costal cartilages above
- 11 and 12 costal cartilages do not articulate with anything—floating ribs
16
Q
Describe the basic anatomy of a rib
A
- Vertebral end closest to vertebral column has a head, neck and tubercle
- head has two articular facets
- Tubercle has two facets—medial facet closest to the head and lateral facet
- Medial facet is smooth—articular surface
Lateral facet is a rough lump of bone—attachment of a ligament
- Medial facet is smooth—articular surface
- Then shaft or body of the rib
- Vertically orientated with a superior and inferior edge and you can see a costal groove on the internal aspect
- Within the costal groove is where the neurovascular structures run
- Anterior or sternal end is characterised by a pit for the costal cartilage to plug into
- Vertically orientated with a superior and inferior edge and you can see a costal groove on the internal aspect
17
Q
Which ribs are described as atypical?
A
- Ribs 11 and 12 and 1 are atypical
- 1st rib only articulates with T1 and do there is only one facet
- Very short and also much more curved than the other ribs and broad and almost horizontal in its orientation
18
Q
What are the costovertebral joints?
Describe their function
What are the costotransverse joints?
Describe their function
A
Costovertebral Joints
- the head of the rib articulates with the demi-facet on two consecutive vertebrae and the IV disc in between-except for T1 that does not articulate with C7
- Radiate ligament-radiates out to strengthen the joint
Constotransverse joints
- Between the transverse process of the vertebrae and the tubercle of the rib
- The medial facet of the tubercle
- Note the 3 part costotransverse ligament that holds together the neck and tubercle
- Blunt trauma will not be able to dislodge this joint
- you will break the rib first
19
Q
What are the attachments of the diaphragm?
A
- Xyphoid process attachment anteriorly
- Arcuate ligaments
- Lateral and medial
- Lateral overlies quadratis lumborum-thickening in the fascia of quadratis lumborum
- Medial arcuate ligament—psoas major-thickeing in the fascia
- Posterior attachment to the lumba vertebral column
- connects via pair of ligaments
- left crus, right crus
- connects via pair of ligaments
20
Q
The Crus originate at ___ with the right crus extending to _____ and the left crus extending to____. This could be due to diagphragm on the right being ____ than that that on the left due to the presence of the ____
A
The Crus originate at L1 with the right crus extending to L3 and the left crus extending to L2. This could be due to diagphragm on the right being higher than that that on the left due to the presence of the liver
21
Q
Where does the IVC, Oesophagus and Aorta pass through the diaphragm?
A
- We have the IVC passing through central tendon at level T8, to the right
- Oesophagus passes through muscular part of diaphragm at T10, to the left
- Aorta between the crura at T12—so not really through the diaphragm. More behind the diaphragm and medially.
22
Q
Explain the quality and direction of each of the layers of the intercostal muscles
A
External
- Front pockets muscle fibres are directed downwards and forwards—like hands in front pockets
- Brown is muscular fibres—muscle fibres form posterior and lateral parts
- And then the rest is replaced by membrane—the green—in the anterior part—external intercostal membrane
- When the external ICM contract they pull the rib below up and out. So the action is to elevate and expand rib cage and is therefore a muscle of inspiration.
Internal
- Fibres are directed downwards and backwards
- Back pockets muscle
- Membrane replaces the muscle posteriorly
- Fibres pull ribs down and in—expiration muscle ??
- But not as strong
- Probably what it does is holds the space taught rather than actually move the ribs—more of a splint rather than an expiration muscle
Innermost ICM
- Incomplete
- Direction of fibres is back pockets
- Only fills lateral part of space
- There are some muscle in the same plane
- Transversus thoracis —anterior aspect in the same plane as innermost ICM
- And
- Subcostalis —posterior aspect of the space
- But probably OK just to remember that they are discontinuous muscles
23
Q
Intercostal neurovascular bundle
A
- Each intercostal space has a bundle—vein, artery and nerve
- From top—down
- This is tucked into that costal groove
- Neurovascular plane runs between the internal and innermost ICM
- Smaller branches (collateral branches) of each of the vein, artery and nerve running in the bottom of the space—usually smaller
- So when passing a needle into the intercostal space we would put needle into bottom of the space and avoid the larger and more important bundle at the top
24
Q
Vein artery and nerve of the intercostal space
Where did they come from?
Where do they go to?
A
Intercostal nerve
- Intercostal nerve is the ventral rami of the thoracic spinal nerve
- It becomes the intercostals nerve
- And we can see that only the innermost intercostal muscle is deep to this
Arteries
- Anterior and posterior aspect of the intercostals space and the anterior and posterior arteries anastomose together. Anterior intercostal arteries come from the internal thoracic artery and the posterior come from the descending thoracic aorta.
Veins
- Veins mirror the arteries and we get them coming posteriorly and anteriorly
- Anterior intercostal veins will drain into the internal thoracic vein
- Posterior intercostal veins will drain into the azygous system of veins
25
What are the movements of respiration and which muscles contribute
* Diaphragm is the main muscle of respiration and contracts the thorax vertically to expand it
* Intercostal muscles also contribute
* Elevation of the upper ribs (ribs 1-7) changes AP dimension of the thorax—i.e. the ribs are connected to the thorax and pulling ribs upward will expand in that direction as the ribs are not horizontal-pump hundle movements
* Lower ribs don’t articulate with the sternum so when they are elevated the middle of the shafts move laterally and expand the lateral part of the thorax—bucket handle movement
26
What does the pericardium attach to and why?
* The pericardium is connected to the central tendon of the diaphragm
* When the diaphragm contracts on inspiration this pericardial sac can stop the diaphragm from descending.
* Pericardial sac is positioned in the middle mediastinum
27
What are the devisions of the pericardium?
* Outer fibrous pericardium
* And inner serous pericardium
* Parietal layer lines internal aspect of the fibrous pericardium
* And then the visceral layer lining surface of the heart
* Arrangement creates pericardial cavity between these two layers—visceral and parietal
* Potential space only—couple of mls—not a large volume
* Friction free surface for the heart to move
* Friction free glide
28
Describe the internal features of the right atrium
* atria are thin walled receiving chambers
* internal aspect of the anterior part of the right atrium are lined with ridges—**musculi pectinati**
* posterior surface is smooth—**sinus venarum**
* **Crista terminalis**—clear defined point where the musculi pectinati end and the sinus venarum starts.
* Superior Vena cava returns blood from head, neck and upper thorax—no valve
* And the inferior Vena cava—returns through the central tendon—remember it goes through the **diaphragm at T8**
* Remember that the central tendon is adherent with the pericardium so the moment the IVC pierces the diaphragm it empties into the atrium
* Rudimentary valve associated with the IVC opening
* This will lead us to the fossa ovalis
* Which in utero would have opened into the left atrium because the baby is not breathing air—i.e. blood is already oxygenated so we bypass the pulmonary circulation and just pump through the body
* Eventually this seals off—can see it in left and right atrium.
* Coronary Sinus is the venous drainage form the heart itself.
29
Describe the internal features of the right ventricle
* Anterior wall has been flapped down
* Thicker walls
* Large number of muscular ridging—**trabeculae carnae**
* At the outflow tract just before the pulmonary trunk begins is a smooth area that does not have the trabeculae carnae and this area is the conus arteriosus/infundibulum. (note every other area has trabeculae carnae, posteriorly and anteriorly.
* Three specialised (atypical) trabeculae carnae are called papillary muscles where their base is connected to the wall but apex projects into the centre
* From the apex of each we have a series of chordae tendinae which connect the apex of the papillary muscles with the tricuspid valve
* Remember that the papillary muscle are just an extension of the trabeculae carnae—i.e. contract together
30
Decribe the features of the left atrium and the left ventricle
* Looking into left ventricle on left and left atrium on right
* Left ventricle has the thickest wall overall—pumping into systemic—higher pressure than pulmonary circulation
* Bi-cuspid atrioventricular valve—mitral valve—mostly cut away—has the chordae tendinae and papillary muscles
* Left atrium simply thin walled and smooth with 4 openings for the 4 pulmonary veins
* Ear like appendage heading around to anterior surface of the heart
31
What is the function of the fibrous skeletocn of the heart and where is it found?
* Pair of atrioventricular valves
* Rings surrounding
* And pair of lunar valves
* Coronets surround pulmonary and aortic valves
* This structure anchors atria and ventricular muscles separately.
* 2 separate muscle masses—separated in their attachment to the fibrous skeleton. Atrial muscle mass forming the atrial chamber and the ventricle muscle mass—separated by fibrous and so are separated from AP passing between them—need something to jump this gap
32
Decribe the atrioventricular valves
on left and right
* Tricuspid on right and bicuspid (mitral) on left
* 3 cusps
* anterior
* posterior
* septal
* Ventricular surface is rough and has attachment of the chordae tendinae
* The chordae tendinae connects to two adjacent cusps separately and the pulls them together to close the valve
33
Describe the semi-lunar valves
* Base is attached to internal surface of the wall of the vessel and the apices meet in the centre
* Anterior, posterior, and left and right (aortic is labelled correctly)
* When ventricle contracts blood is pushed through the pulmonary and aortic valve when the pressure increases to above the pressure in the vessels. And then when we get a decrease in pressure in the ventricles then the valves just close off.
* In the aortic valve the coronary arteries arise and then these arteries deliver blood to the heart
34
Describe the conduction system of the heart
* SA node in the right atrium and right at the top of the crista terminalis
* The AV node is also in the right atrium
* The bundle of His is what allows the conduction system to bridge across the fibrous skeleton and then bundled branches (purkinje fibres) take the AP down to the ventricles
35
What is the nervous supply of the heart?
* The cardiac plexus is situated at the base of the heart and is divided into a superficial and deep part. It receives branches from the vagus and sympathetic trunk
36
Describe the coronary arteries, draw them
* The very first branches of the aorta
* They emerge onto the anterior surface of the heart either side of pulmonary trunk
* Right coronary artery descends in the anterior atrioventricular groove (coronary groove)
* There is a marginal branch that comes of the right coronary artery which runs along inferior border of the anterior portion of the hear
* And the right coronary artery will give off another branch that leads to the left coronary artery and runs along the posterior interventricular groove
* In 60% of cases we will see a branch come off the start of the right coronary artery and then run between ascending aorta and right atrial appendage to supply the SA node and in 90% of cases the right coronary artery will also supply the AV node
* Left coronary artery also starts at the anterior of the heart but then splits into circumflex branch and an anterior interventricular branch.
* The circumflex branch moves posteriorly and then meets with the right coronary artery in the posterior atrioventricular groove
* May be other branches also
37
What is the parasympathetic control of the heart?
When are the parasympathetics exerting control over the heart?
* Two fibre system
* pre-ganglionic and post ganglionic
* Pre-ganglionic neurons release ACh which acts on the post ganglionic neurons and this results in ACh release and action on MuscR which result in slowing of HR, through action on the SA node and AV node
* The parasympathetic nervous sytem is constently acting upon the heart slow HR-evident through the application of "atropine" a parasympathetic blocker
38
What is the sympathetic control of the heart?
When does this system act on the heart?
* two fibre system
* pre ganglionic fibres release ACh which acts on Nicotinic receptors, they then act to release NA which acts on Beta and alpha adrenoceptors
* Innervates the SA node, conducting tiussue and myocardial cells
* Increase HR and increase contractile force (positive ionotrope)
* When blocked by propranolol the HR decreases a bit indicatign that sympathetic fibres are not that actie at rest
39
Which fibres (sympathetic or parasympathetic) have more of an effect on HR at rest?
* The parasympathetic nervous system
40
Describe the phases of an Action potential in the spontaneously depolarising SA node
* The SA node is the key cell type that regulate rate and if we block the autonomic nerved the cells will depolerise at 100bpm
* Resting membrane potential of -60
* At resting there is a bit of Na and a bit of Ca leaking down an electrochemical gradient (i.e. the cell is negatively charged compared to the extracellular environment)
* Eventualy the Na and Ca leaking reaches a threshold and Ca then floods in.
* And then we get repolerisation--i.e. opening of the pottasium channel
41
How do the parasympathetics actually slow the HR?
* ACh acts on muscurinic **M2 receptors** (G-protein coupled)
* decreases cAMP leading to opening K+ channels
* leads to hyperpolarisation K+ leaves and slows Na and Ca influx
* So now it takes longer for the cells to reach threshold (phase 4)
42
How does the sympathetic nervous system result in increased HR?
* Acitavation of **Beta1 Adrenoceptors** (G-protein coupled) increases cAMP production leads to opening of Ca channels
* Ca entry speeds up rate of firing
* Increases the slope of phase 4 depolarisation
* increases rate of firing of SA node and more rapid conduction AV node
* can trigger dysrythmia if pushed too hard
43
Describe the ventricular action potential?
* The ventricular myocyte AP has a stable resting membrane potential.
* Phase 0-depolerization-Na in
* Phase 1-rapid repolerisation-K out
* Phase 2 plateu-Ca in K out
* Phase 3-repolerisation K out
* Phase 4-stable membrane potential
44
What are the common symptoms of dysrythmia?
* Shortness of breath, fainting, fatigue, chest pain
45
What are some of the possible mechanisms for dysrythmias?
* Altered impulse formation
* Automaticity of pacemaker cells
* Abnormal generation of action potentials at sites other than the SA node
* Altered impulse conduction
* Conduction block
* Ventricles adopt own slower rate
* Re-entry
* Extra beats increase rate
* Triggered activity
* Early or late after-depolarisations
* Excess sympathetic activation
46
What are the four main types of antidysrhythmics drugs?
1. Na+ channel blockers-reduce phase 0 slope and peak of ventricular action potential:
* 1a moderate block
* 1b weak block
* 1c strong block
2. Beta-adrencoceptor antagonism-decrease rate and conduction (SA node)
3. K+ channel blockade-delay phase 3 of ventricular action potnetial and prolong APD
4. Ca2+ channel blockade-most effective at SA and AV nodes-reduce rate and conduction
47
What are the effects of the different Na+ channel blockers?
What can be the side effects of these drugs?
* Predominatly used for **ventricle arrythmias**
* Class 1a lengthens the repoleraisation and so lengthens the effective refactory period-this class is probably the one that is most effective at the SA node AV node dysrythmias but they are all mostly for ventricular AP modification
* Can get many different side effects at different doses
* effective does is 2-3 ug/ml
* Na+ channel blockers will have many systemic effects
* 4ug/ml Lip and tongue numbness
5ug/ml Light headedness
7ug/ml Visual disturbance
8ug/ml Muscular twitching
10ug/ml Convulsions
15ug/ml Coma
20ug/ml Respiratory arrest
25ug/ml Cardiovascular depression
48
What are the main effects of the Beta adrenoceptor antagonists? how do they exert their anti-dysrhthmic action?
Adverse effects?
* Prevent β1-adrenoceptor effects on SA & AV nodes
* Decrease sinus rate, conduction velocity & aberrant pacemaker activity
* Also have membrane satbilising effects on the Purkinje fibres and so they can also block sodium channels
* Adverse effects
* Bradycardia, reduced exercise capacity, AV conduction block, hypotension
* Bronchoconstriction(poor selectivity?), Hypoglycaemia
49
What are the main effects of the K+ channel inhibitors? how do they exert their anti-dysrhthmic action?
Adverse effects?
* prolong cardiac action potnetial
* slow phase 3 repolarisation
* decrease incidnece of re-entry
* increase risk of triggered events
* So mainly used for ventricular re-entry dysrythmias but may also trigger these events too
* Amiodarone is also shown to block Na+, Ca2+ and B-adrenoceptors
* reversible photosensitisation, skin discolouration and hypothyroidism
* pulmonary fibrosis with long term use
50
What are the main effects of the Ca2+ channel blockers? how do they exert their anti-dysrhthmic action?
Adverse effects?
* Cardioselective-act preferentialy on SA and AV node and have effects on the initiation of AP.
* Can also slow connduction and increase refactory period
* Facial flushing, peripheral oedema, dizziness,bradycardia, headache, nausea
51
What is Hypertension?
* BP\> than 140/90 mmHg
* risk factor for
* stroke, TIA
* MI, Ischaemic heart disease, CHF
* aortic aneurism, retinal heamorrhage
* renal failure
* death
* Multifactorial disease
* often no known cause
* Risk factors
* smoking, diet, weight, stress
* Treatment benefirs are **unequivocal**
* less morbidity
* fewer deaths
52
What are some of the risk factors for hypertension?
* Smoking
* Diet
* Weight
* Stress
53
Describe the neural and hormonal regulation of blood pressure?
* Baroreceptors sense the pressure change and signals to the brainstem.
* Sympathetic nervous activation
* Noradrenaline is released which can act on alpha1 adrenoceptors to constrict blood vessels, increase cardiac output with B1 adrenoceptors.
* NA also acts on **B1 adrenoceptors in the kidney** which secretes Renin
* Activates AngII and causes increased constriction of blood vessels though AT1 receptors.
* AngII also works on kidney to conserve water and perhaps direct effects on the heart too
54
What is the ABCD of anti-hypertensive drugs?
* Angiotensin system inhibitors
* Beta-adrenoceptor antagonists
* calcium channel blockers-blood vessels also have L type calcium channels and regulate tone of arteries-calcium influx leads to vessel constriction
* Diuretics
55
How do ACE inhibitors work to reduce blood pressure?
What are the adverse effects?
* Renin works on angiotensinogen which makes angiotensin I and then ACE converts to AngII and then that acts on AT1 receptors and causes vasoconstriction and release of **aldesterone** which acts on the kidney and casue salt and water retention
* AngII also causes increase of Sympathetic nerve activity-**positive feedback**
* ACE inhibitors are called **"prils"**
* prevent conversion of AngI to AngII
* Reduce vascular tone
* Reduce aldosterone production
* Reduce cardiac hypertrophy
* through reducing further sympathetic nerve activation
**Adverse effects**
* Most of the side effects due to the fact that ACE inhibitors also prevent the breackdown of bradykinin by ACE (ACE is a kininase) (bradykinin is a vasodilator and also involvged in the pain responses)
* First-dose hypotension
* Dry cough
* Loss of taste
* Hyperkalaemia (+ thiazide diuretic)
* always prescribed with a diuretic to control hyperkaaemia
* Acute renal failure
* Itching, rash, angio-oedema
* Foetal malformations
56
How do AngiotensinII receptor antagonists work?
What are they called?
What are the side effects?
* Block the AT1 and AT2 receptors
* Clinically they block the vasoconstriction effects of AngII working to constrict the blood vessels
* But also reduce aldesterone release as well
* Reduce vasoconstricttion
* Reduce aldosterone
* Reduce cardiac hypertrophy
* Reduce sympathetic activity
**Adverse effects**
* still get hyperkaleamia so still need thiazide diuretic
* this is due to blocking of aldesterone release due to the fact that aldesterone promotes K secretion into the urine
* headache and diziness
57
What are the contrandications for ACE inhibitors and AngII receptor antagonists
* pregnancy
* bilateral renal stenosis
* impaired renal function already, dont want to make it worse by inhibitng theprimary regulatating system of the kidneys
* angioneurotic oedema
58
What are the effects of Beta adrenoceptor antagonists?
Side effects?
* called "olols"
* Mechanism
* Reduce cardiac output
* Rate, contractility
* Reduce renin release
* Blood volume, TPR
**Side effects**
* Cold extremities
* could be due to the reflex constriction of peripheral arteries due to blood volume reduction
* could also be due to the blocking of the B2 adrenoceptors that cause vasodilation in blood vessels
* Fatigue
* reduced exercise capacity due to reduced CO
* Beta-2 blockade of receptors in arteries supplying muscles limiting vasodilation and thus blood supply
* Dreams, Insomnia-related to lipid solubility
* Bronchoconstriction-Beta-2 adrenoceptors in bronchus-**contradicated in asthma**
59
What are the effects of L-type calcium channel blockers?
Side effects?
* Inhibit voltage-gated L-type Ca2+ channels in myocardium and vasculature
* Two subclasses that are either more cardio selective or more vascular selective
* Reduce cardiac/vascular contractility
* Reduce vascular resistance
**Side effects**
* oedema, flusing and headache, all due to the increased dilatation, headaches increased cerebral pressure etc
* also the L-type calcium channel blockers that are are more cardio-selective can give a bradycardia
* More vascular selective drugs can result in a reflex tachycardia
60
What are the effects of Diuretics on BP?
Side effects?
* Inhibit Na+ and Cl- transporter in the distal convoluted tubule and causes reduced reabsorption
* We get increased water and Na and Cl loss
* lower blood volume and stroke volume and blood pressure
* can get K loss as well and so are also pprescribed with ACE inhibitors and AngII antagonists
**Side effects**
* loss of K+
61
What are the three the heart is seperated into?
1. Epicardium (outer layer) a simple squamous epithelium, subepicardial connective tissue, blood vessels, fat, nervous tissue
2. Myocardium-muscle cells and capillaries
3. Endocardium (inner layer) an endothelial layer, subendocardial connective tissue, conducting tissue
62
Lable the Heart tissue
63
What are the histological features of a cardiac muscle cell
* Cells are small
* They have a central nucleus
* Form branching fibres
* Joined by intercalated discs
64
What is the role of gap jucntions in cardiac muscle cells?
* Gap junctions are at intercalted discs are there to electrically connect the cells and coordiante beating.
* However, the gap junctions only co-ordinate electrical activity on a local level
* To co-ordinate contraction of different chambers a separate conducting system is needed – Purkinje fibres
65
The heart will beat at the rate of the _____ beating cells and these cells are located in the ___ and the \_\_\_\_
* fastest
* SA node
* AV node
SA node is the fastest though and the AV node follows unless the SA node expires and the AV node must take over
66
What are purkinje fibres?
Where do they form bundles?
* Modified cardiac muscle cells - larger
* Limited contractile machinery
* Full of glycogen
* Form bundles in subendocardium
67
What are the three layers of a blood vessel?
* tunica intima
* tunica media
* tunica adventitia
68
Describe the intima layer in terms of its composition
* Comprosed of a monolayer of squamous epithelium (endothelium)
* This sits on basal lamina and is supported by a thin layer of connective tissue
69
What is the role of the endothelium?
* Actively inhibit clotting by secreting inhibitors
* Prime underlying connective tissue with Von Willebrand's factor (activates clotting)-so when there is rupture of the vessel there is clotting
* Release vasoactive substances like endothelin (vasoconstrictor) and nitric oxide (vasodilator) which act on underlying smooth muscle
70
Describe the media in terms of composition and function?
What is the special (unique) thing that it does?
* Middle layer, consisits if smooth muscle arranged concentrically (or helically)
* Contricits the lumen
* Decrease in lumenal diameter, increase the resistance- blood pressure up
* The smooth muscle secretes the connective tissue in which it is embedded (collagen type III, elastin and ground susbtance)
* It can vary from a single layer of smooth muscle to up to 40 to 50 layers
* In the situation of atherosclerosis the smooth muscle synthesis can get a bit out of control
71
Describe the adventitia in terms of composition and function
* Contains connective tissue (collagen type I and elastin, plus ground substnace), with embedded fibroblasts
* Anchors to surrounding tissue
* Has own blood supply (vasa vasorum) in larger vessels
* blood vessels for blood vessels
72
Descibe the genral composition of arteries and relate this to their function
Compare ellastic arteries to muscular arteries
* Arteries themselves vary in their structure depending on where they are in the circualtion
* genrally arteries have to withstand high, rapidly changing blood pressures
* they also regulate the blood pressure by constricting or relaxing
* **Elastic arteries** are closest to the heart as they have to withstand the highest blood pressure fluctuations
* blood pressure rises during Heart contraction but does not drop to 0 when the heart is in diastole
* this is due to the arteries bouncing back (due to there ellastic nature)
* blood flow is continuous but pulsatile
* **Muscular arteries** are further from the heart
* Distribute blood into the tissue
* Little elastin in the media
* Contractions of the smooth muscle in the media regulates the blood pressure and regulates blood supply to organs
73
Describe the composition and function of the arterioles?
* Arterioles still have all 3 layers but only one layer of smooth muscle in the media
* Arterioles can also contract and relax
* Because there are so many arterioles they are the main regulators of blood pressure
* less than 0.1mm in diameter
74
Describe thr composition and function of the capillaries
* Capillaries arfe often thinner then the diameter of a RBC and so force contact between the vessel wall and the RBCs
* capillaries only have a single smooth muscle cell controlling blood flow associated with it
* may be a **meta arteriole** between the arterioles and the smooth muscles
* capillaries are formed by a single endoothelail cell wrapping around to form a thin tube and sealed with tight junctions
* sitting on a basal lamina
* sometimes has a pericyte (media)
* a few collagen fibres surround the vessel (adventitia)
*
75
What a fenestrated capillaries?
* Found in pancreas, intestines and endocrine glands
* Diaphragms are not just simple membranes. They contain 8 wedge shaped channels
* sometimes the diaphragm is completely missing (like in the kidney)
76
Describe the composition and therefore function of veins?
* Blood from capillaries is collected in the veins
* veins carry deoxygenated blood at **low** pressure
* contain 70% of the blood
* act as a blood resovoir
* Has the same layers as arteries
* media is thinner, adventitia is thicker (to help withstand hydostatic pressure)
* valves to force blood in one direction
* assisted by skeletal muscle contractions
77
Decribe the composition and function of the venules?
* Blood from capillaries collected by venules
* equivalent to the capillaries in that they have a pericyte in the media rather than smooth muscle
* although later on they do acquire smooth muscle
* ussually larger lumen than arterioles
* are the site for diapedesis and so express ICAMs and integrins for leukocyte entry into tissue
* affected by histmaine and other cytokines
78
Describe the compositiona and function of medium to large veins
* Subendothelial connective tissue is well developed
* adventitia enlarged, often at expense of media
* to cope with hydrostatic preessure
* sometimes, longitudinal smooth muscle bundles in the adventitia (stiffening)
79
Describe the composition and function of the lymphatics
* capillaries are thin walled and leaky
* so lots of fluid can accumulate in the intercellular space
so lymphatics drain extracellular fluid back into the circulation
* lymphatics also have valves and skeletal muscle contraction which assists in bringing fluid back to large veins in thoracic cavity and abdominal cavity
* No red cells, lymph and WBC
* Very thin epithelial wall forming endothelium and gaps between allow fluid to come back in and valves are present and so we pump fluid back
* large ones look like veins
* usually collapsed post mortem
80
What is arteriosclerosis?
* intimal damage and thickening in the **arteries**
* with fibrosis
* commonn ageing or with hypertension
* Impair arteries so they cannot relax and contract because there is too much collagen
* Can narrow lumen and impair blood supply to downstream tissues
81
What is Arteriolosclerosis?
What are some of the resulting sequale?
* intimal damamge and thickening of the **arterioles**
* Smooth muscles have produced too musch matrix and proteins from blood (albumin, Immunoglobulins) can leak across damaged endothelium
* known as hylanine arteriolosclerosis
**Sequale**
* poor blood supply to tissues (ischeamia)
* benign nephrosclerosis-ischaemia of the functional units of the kidney due to narrowed arterioles
* possibility of microaneurysms and then bleeding
* cerebral heamorrhage
*
82
What is atherosclerosis?
What are the stages of formation?
* build up of inflammatory, fibrotic, necrotic and fatty material in arteries
* Fibrous and gunky
* from the latin for ''hard porridge''
* **Fibrous cap and necrotic lipid core**
**Stages of formation**
1. Fatty streak
* Collection of foam cells in the **intima**
* macrophages that have ingested lipid
* very common so not clinically significant
2. Damage, Inflammation, cholesterol and fibrosis
3. Stable atherosclerotic plaque
* Fibrous cap
* chronic inflammatory cells
* necrotic lipid core
* likely asymptomatic
* can encroach on lumen over time
* still have lumen though becasue in the early stage the plaque actually grows outwards
4. Unstable atherosclerotic plaque
83
What are the two kinds of calcification and what can they be a result of?
* **Dystrophic calcification**
* appears in areas of cell degeneration
* e.g. tuberculosis, breast lesions, atherosclerosis
* **Metastatic clacification**
* ussually as a result of kidney disease
* serum calcium and phosphate levels are too high
* They reach their precipitation threshold and fall out of
solution: calcification in blood vessels, kidneys, other
84
85
What makes a plaque unstable (i.e. vulnerable to rupture)?
* thinner fibrous caps
* or even ulceration
* Larger necrotic core
* more inflammatory cells
* less than 50% stenosis
* i.e. likely to be asymptomatic
86
What is an acute plaque event and what can it lead to?
* APE can be: plaque rupture, haemorrhage into plaque and erosion of endothelium
* this can lead to clotting **(thrombosis)**
* or the plaque can fly off and clot somewhere else **(thromboembolism)**
* or atheroembolism-peice of plaque can fly off and get caught **(atheroembolism)**
87
What levels of stenosis results in chronic ischeamia of an organ being supplied?
* \>70% stenosis
88
What are some of the other sequale that could result from athereslcerosis (other than thromboelbolism and atheroembolism)
* anuerysm and rupture
* result of wall weakening
* Occlusion by thrombus
* Critical stenosis
* blood vessels becomes completely clogged
89
What is the role of the endothelium in the initiation of atherosclerosis?
* Endothelial dysfunction is important in the start of atherosclerosis
* normal endothelium does not interact with immune cells
* **but if you make it angry then it will be leaky and inflammatory cells will enter etc**
* leaky
* expresses adhesion molecules
* produces cytokines and growth factors
* changes from anti-coagulent to pro-coagulent
* **Takes up more LDL**
* which become oxidised
* and then pro-inflammatory
* **Allow monocytes into intima**
* expression of adhesion molecules
* monocytes enter intima and become macrophages
* macrophages phagocytose oxidised LDL and produce inflammatory cytokines
* Endothelial dysfunction risk factors include
* hypertension has a low grade shear effect
* smoking has toxic and pro-inflammatory effects
* high blood sugar and lipids can damage endothelium
90
How does cholesterol/LDL influence the progression of atherosclerosis?
* LDL accumulates in the intima and is oxidises
* and then taken up by macrophages and smooth muscle cells
* and they becoem foam cells and this stimlates inflammatory cytokines and the production of free radicals
* The oxidised LDL is also toxic to the endothelial cells
91
How do inflammatory cells contribute to the progresison of atherosclerosis?
* T cells help macrophages to call more T cells etc-chronic inflammation
* attract more inflammatory cells
* more ROS
* more cytokines
* more MMPs
* perpetuates inflammatory cycle
92
How do smooth muscle cells contribute to the progresison of atherosclerosis?
* smooth muscle cells come in and produce collagen when damage occurs to the intima
* so produce thick fibrous cap
* so probably a good thing so we can wall off the thick necrotic debris
* collagen-thicker fibrous cap
93
Diagram of atherosclerosis
94
What is an Aneurysm?
* Abnormal dilation of a blood vessel
* can also get them in heart
* Can get true aneurysm or a false aneurysm
* True aneurysm is when the whole wall stretches out-without bursting
* can be saccular-one side
* fusiform-both sides
* False aneurysm is where it has ruptured
* dissection
* heamatoma
* Weak media-lack of blood supply due to inflammation due to atherosclerosis or congenital etc
* weak media due to intimal thickening
* risk is that the aneurysm can rupture and blood will leak out
95
How does an AAA come to be?
* associated with atherosclerosis
* inflammatory environment weakens ECM
* MMPs
* intimal thickening interferes with wall perfusion
* Risk of rupture increases above 5cm diameter
* often contain thrombus which can embolise
96
What is a berry aneurysm?
* in cerebral circualtion
* weakening of a congenital defect
* major cause of subarachnoid haemorrhage
97
What is a Dissection?
what is the common site?
what are some of the possible consequences
* Blood leaves intima (due to rupture) and gets into the media
* Aortic dissection is common and is strongly associated with hypertension
* can involve or compress important arteris
* can rupture into pericardium
* cardiac tamponade
* can rupture into thorax
* exsanguination
98
When does our heart undergo hyperplasia?
When does our heart undergo hypertrophy?
* hyperplasia should cease after a few months of life
* through childhood heart undergoes hypertrophy
99
What are some of the casues of LV hypertrophy?
* Myocadial infarction
* Cardiac damage eg myocarditis
* Volume overload
* pressure overload
100
What are the two different types of LV hypertrophy?
describe what actually happens in each and some of the common causes
* Concentric hypertrophy
* increase LV mass
* Increase wall thickness
* often due to pressure overload
* more sarcomers in parallel
* Eccentric Hypertrophy
* increase LV mass
* Normal relative to wall thickness
* often due to volume overload
* myocyte stretching-more sarcomeres in series
* Remodelling
* Normal LV mass
* Increase in relative wall thickness
101
What is meant by hypertrophic decompensation
* LV hypertrophy (concentric) is meant to compensate for a high pressure afterload
* meant to maintain systolic function, cardiac output and LVEDP
* LV hypertrophy (eccentric) is compensation for volume overload
* meant to increase LVEDV and increase EF
* But sometimes with chronic hypertrophy we can get decompensation where LVEDV increases and LVESV increases but ejection fraction decreases
* reduced systolic function and cardiac output
* LVEDP must increase even more and we end up with cardiac failure
102
What are the casues of LV hypertrophy?
conccentric and eccentric?
**Environmental**
* Concentric-pressure overload, high afterload
* hypertension, aortic stenosis
* eccentric-volume overload, high preload
* mitral and aortic regurgitation, ventricular septal defect
* Following myocardial infarction
* following cardiac injury
* obesity, diabetes, renal failure
* Infiltration
**Genetic**
* Hypertrophic Cardiomyopathy
* Fabry's disease
*
103
How can we identify LVH?
* Clinical-forceful apex beat, S4, S3
* ECG-tall voltages, T wave inversion
* tall QRS due to hypertrophy
* CXR
* larger heart in eccentric LVH
* may be normal size in concentric LVH
* Echo
* MRI
* Cardiac CT
104
LVH hypertrophy is a marker for cardiovascular events
* concentric hypertrophy is the worst at causing mortality following myocardial infarction
* LVH is a marker for increasing severity of CVD
105
Explain the concept of Diastolic dysfunction
* thick muscle is stiff and harder for the ventricle to relax and full with blood so pressure required to fill ventricle is higher.
* higher LVEDP required to achieve same LVEDV (preload)
* So increased LA and pulmonary vein pressure
* can lead to pulmonary congestion
* Atrial kick now also more important and this can lead to atrial fibrillation
* sensitive to dehydration due to low BP and also sensitive to fluid loading-i.e. pulmonary congestion due to too much fluid
106
How do we treat LVH?
* must treat underlying condition
* valves etc
* Hypertension
* Weight loss
107
What is LEft Ventricular remodelling?
* Pretty mushc the same as LVH eccentric hypertrophy
* but used as a term to describe what occurs after myocardial infarction
* heart dilates around infarct zone and the rest of the heart also dilates
* Though angiotensin has a role as ACE inhibitors seems to prevent remodelling-often with Beta blockers as well
108
Explain RB hypertrophy
Causes?
**Causes**
* congenital
* transposition of the great arteries
* Pulmonary hypertension
* lung disease
* pulmonary embolus
* chronic L heart failure
* Right heart valves
* Pulmonary Stenosis/Regurgitation
* Tricuspid Regurgitation
109
What is Hypertrophic Cardiomyopathy?
Cause
What happens
**Cause**
* Autosomal dominant
* Positive family history
* Mutation in genes for sarcomere proteins
* \>900 mutations in 12 genes (since 1990)
* Most common
* Beta cardiac myosin heavy chain
* cardiac myosin binding protein
* cardiac troponin I and T
**What happens**
* Hypertrophy of the ventricular septum
* cellular hypertrophy
* myocyte dissarray
* LV outflow tract obstruction
* i.e. all the extra muscle get in the way
* Diastolic Dysfunction
* **Ventriuclar arrythmias-sudden death**
* same mutations can cause varied symptoms
* symptoms can vary from mild to severe
* common cause of sudden death inn athletes
*
110
What is athlete's heart?
* large and thickened heart
* particularly the right ventricle often becomes smaller after training is stopped but not always
*
111
What is Starling's Law?
* Responsible for the cardiac output vs left ventricular end diastolic volume relationship
* Responsible for
* CO=venous return
* Left heart output=right heart output
112
How do we measure right ventricle pressure?
How do we measure left ventricle pressure?
* Use JVP as a indirect measure
* Use pulmonary artery wedge pressure
* Catheter wedged into pulmonary artery will measure the pulmonary venous pressure
* so occlude the pulmonary artery and we can measure the left ventricle pressure indirectly
113
What are the pressures acting across the capillary wall?
What pressure predominates at the arterial end and what pressure predominates at the venous end of the capillary?
* Hydrostatic pressure pushing out
* pressure of the fluid pushing non the capillary wall
* osmotic pressure pushing in
* Hydrostatic pressure dominates at the arterial end so fluid is pushed out of the capillary
* at the venous end osmotic pressure dominates and so fluid is pushed back in
* So most of the arterial pressure is lost across the cappilaries
114
What pressure changes can cause oedema in tissues?
* Increased pressure in the venous system causes fluid to leak out rather than fluid to come back in (through osmotic pressure)
* could be due to heart failure
* Decreased osmotic pressure
* plasma protein loss: renal failure
* Blocked lymphatics (fluid leaked into tissues is no longer transported back into tissues)
* cancer
* Increased capillary permeability
* Infection
115
What effect will an increase in LVEDP have on the lungs?
* if we have more EDP in the left ventricle then that means more pressure pushing fluid out of the pulmonary capillary and and this could lead to congestion
116
So what are the two uses of the EDP pressure measurement in each of the LV and the RV.
What happens in each case if they are elvated?
* LVEDP=Preload: LV function
* LVEDP=LAP=PVP: Lung capillaries (increase pressure in the capillaries will cause increase fluid leak and potentially pulmonary oedema)
* RVEDP=Preload: RV function
* RVEDP=RAP=JVP: Peripheral capillaries where increased pressure will cause fluid leak and peripheral oedema
117
What is cardiac failure?
* Cardiac output is less than the body needs
* Usually due to decreased CO
* rarely due to increased body needs
* usually systolic failure
* loss of contractility
118
What does the body do when we get cardiac failure (i.e. the heart contracility decreases) to compensate
* The body must retain fluid and increase venous return and increase LV end diastolic pressure.
* But if the LVEDP increases too much (i.e. above 20-25mmHg) than the CO does increase but at the expense of the lungs and fluid will build up and leak into the alveoli and patients will present with **shortness of breath**
119
Remember that pulmonary oedema and peripheral oedema are due to high ____ pressure but high ____ pressure is one of the casues of heart failure and so will eventually lead to ventricular failure
* venous pressures
* arterial pressures
120
What are some of the causes of cardiac failure?
* **Loss of myocardial muscle**
* Ischeamic heart disease
* Cardiomyopathy
* dilated cardiomyopathy where the heart becomes very thin and dilated and heart loses muscle
* **Pressure overload**
* Aortic stenosis
* Hypertension
* **Volume overload**
* Valve regurgitation
* Shunts (e.g. septal defects)
121
What are the clinical features if heart failure?
* Left hear failure
* shortness of breath-can be very severe
* fatigue
* tachycardia
* Lung crepitations-crackles due to fluid
* Right heart failure
* Peripheral oedema
122
What is the renal response to Cardiac failure and why is this bad?
What are the 3 ways it is bad?
* Decreased CO
* decreased renal blood flow
* activation of the renin/angiotensin/aldesterone system
* Fluid, Na+ retension
* K+ loss (echanged with Na+)
* Angiotensin causes Vasoconstriction (AT1 receptors)
* These adaptions result in in more fluid(due to water retention), potential for arrythmia (due to K+ loss) and vasoconstriction leads to higher afterload and makes it harder for the heart to work.
123
What is the sympathetic NS response to CF and why can that be bad?
* Increase NA
* Initial increase in contractility
* long term deleterious effect
* vasoconstriction (Beta2 receptors in vessels)
* ventricular arrythmia
* direct toxic effect of NA on the heart muscle
124
What are some of the mechanisms for Right heart failure?
There are 3 main groups with a couple of causes each (for 2 of the three anyway)
* Global heart disease
* e.g. cardiomyopathy
* Specific right heart disease
* RV cardiomyopathy
* right sided valves; shunts
* pericardial disease
* pulmonary hypertension (arterial)
* Lung disease: cor pulmonale
* Pulmonary embolism
* Left heart disease
* causes high pressure in the LV, LA and Pulmonary venous system
* pulmonary venous high pressure causes pulmonary congestion
* chronic hypoxia
* will lead to physiological response where we get pulmonary vasoconstriction
* Endothelin
* lead to pulmonary arterial hypertension
* right heart failure
125
What is the treatment for CF?
* Diuretics (frusemide)
* Aldosterone antagonists e.g. spironolactone
* Angiotensin convertinf enzyme inhibitors (ACE Inhibitors) captopril, ramipril
126
What is a "pril"
* ACE inhibitor
127
What is a "sartan"
* a angiotensinII receptor antagonist
128
Cardiovascular Block
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