Cardio Flashcards
HI
Discuss the layers of cardiac tissue and briefly describe their function
off Y2 presentation/own notes
Keep in mind pericardium has 3 layers.
Visceral and parietal serous pericardium are continuous -and form sinuses at fold. Transverse pericardial sinus is used during cardiac bypass surgery to clamp greater vessels. Pericardium is sac surrounding heart sits within middle mediastinum. Its overall function is protection, anchoring the heart, preventing distension of heart chambers and reducing friction of heart while beating.
From superficial to deep:
- fibrous parietal pericardium: secures heart to middle mediastinum in thorax
- parietal layer of serous pericardium: produces serous fluid
- pericardial cavity: space between serous layers: in cardiac tamponade can restrict heart movement, increasing afterload and decreasing contractility due to increased stress and decreased blood volume preload
- epicardium/visceral layer of serous pericardium: outermost, made of mesothelium and thin connective tissue - simple squamous serous epithelium. Adheres to heart.
- myocardium or cardiac muscle: thickest layer, muscular, forms bulk of heart, responsible for pumping action. Comprises cardaic myocutes- with contractile fibres in cytoplasm, connected by gap junctions to permit ion flow
- endocardium: innermost layer, comprising endothelum (simple squamous epithelium) and thin connective tissue (similar to epi)– provides smooth lining for chambers and vessels
HI
Describe the chambers of the heart
Yr2, own notes, and previous exams (2)
Each atrium has a auricle that protrudes towards their corresponding great vessel – implications for stasis and clotting. Atrial fibrillation clotting occurs in atrial auricles, hence why patients are placed on anticoagulants.
Right Atrium – fossa ovalis (found in interatrial septum; if patent is a congenital defect, risk of paradoxical PE from DVT), crista terminalis, (ant. portion) atrium proper contains auricles and pectinate muscles, (post. portion) sinus venarum and openings for SVC, IVC and coronary sinus, receives blood from coronary sinus, IVC, SVC, tricuspid valve
RA opens to RV via right AV orifice and tricuspid valve that surrounds the orifice.
Right Ventricle – trabeculae carneae, 3 papillary muscles (septal, anterior, posterior, attach to extensions of valves = chordae tendinae), conus arteriosus (smooth outflow tract), low pressure thin ventricle, pulmonary valve
Left Atrium – pectinate muscles only in auricle (as opposed to all of RA), receives blood from pulmonary veins, bicuspid valve. Opens to LV via L AV orifice and mitral valve.
RA and LA divided by inter-atrial septum.
Left Ventricle – apex and diaphragmatic surface, trabeculae carneae, 2 papillary muscles, higher pressure thicker wall, aortic valve.
RV has three papillary muscle groups, LV has two groups.
LV has thicker wall because ejectin blood to systemic vs pulmonary circulation.
LV and RV are divided by interventricular septum.
HI
Describe the anatomical position of the heart
Yr2 presentation
Heart occupies middle mediastinum
Anteriorly: Sternomanubrial joint (2nd costal cartilage or T4/5)– Xiphoid process
Posteriorly: T4-T9 vertebrae
What is the mediastinum? - portion of thoracic cavity excluding the lungs
Phrenic nerve anterior to hilum of lungs, vagus nerve posterior
Clinical relevance: perform this exercise, find sternal angle, move left into 2nd intercostal space, count down to 5th intercostal space in midclavicular line: APEX beat!
Auscultation is not the actual location of the valves-> rather where the sound projects to.
JVP tells you about the pressure of the right atrium!
Blood pressure is correlated with pressure from left ventricle: BP should be taken at heart level!
HI
Describe the heart valves
Yr2 and own notes
- Valves open when pressure in chamber before is greater than next chamber
- Valves snap shut to prevent backflow
- Supported by annulus fibrous rings
- Lub dub = S1 + S2
- S1: Atrioventricular valves closing (Mitral then Tricuspid)
- S2: Semilunar valves closing (Aortic then pulmonary)
- AV valves are maintained by chordae tendinae, which attach to the edge of the ventricular surface, anchoring them to the tips of the papillary muscles
- papillary muscles contract during systole preventing prolapse of AV valves into atria
- semilunar valves open upon pressure from blood leaving ventricle
- backflow of blood closes the valve
- coronary arteries fill from aortic sinus during muscle relaxation/diastole
Clinical relevance: 2 main pathologies
1. Stiff valves that don’t open well: stenosis
2. Floppy valves that don’t close properly: regurgitation
3. Bicuspid valve aortic = aortic stenosis or regurgitation
HI
Describe the coronary arteries and their supply
Yr2, own notes, exam questions
Otherwise known as coronary vasculature. the RCA and LCA are two main coronary arteries.
They branch off the aorta, and they are the first branches of the ascending aorta.
Coronary arteries feed the heart wall, from the outside in.
The arteries branch within the wall and anastomose, and are collected in coronary veins.
* The right coronary artery travels in the coronary sulcus and into posterior IV groove
- supplies most of the heart i.e. RA, RV, IVS, SA and AV nodes
* The left coronary artery supplies the LV, LA and IVS
* The right coronary artery branches off into three: R. marginal branch and Post. IV (or Post. descending), sinoatrial branch
* The left coronary artery branches into circumflex, marginal and LAD(or Ant IV)
- LAD is most commonly occluded artery
The coronary veins parallel the arteries (count 6, including coronary sinus):
- three mains: small, great and middle
- branch off coronary sinus, which sits in coronary sulcus
- there are also ant. IV veins (off great vein) and right marginal vein off small cardiac vein
Think LCA supplies left chambers and IVS
IVS supplied by both arteries
RCA- everything else
Side note:
- 85% are right dominant: RCA supplies posterior IV groove
- small percentage of populaiton: co-dominant/shared dominance
Inferior = RCA or LCx : II,III aVF
Lateral = LCx or diagonal branch of LAD: I aVL V5-V6
Septal /Anterior = LAD: V1-4
HI
List and describe common congenital heart defects
Yr2, own notes
- Most common developmental defects
- septal defects make up 53%: e.g. atrial opening, or opening between ventricles
recall: patent ventricular foramen usu. occurs in membranous portion - AV canal defects make up 13% e.g. atrial and ventricular septal defects, common atrioventricular valves
- LVOTO in 25% of cases: issues of outflow tract obstruction
- conotruncal malformations (36%)
Note the changes that occur on birth:
- Oxygenated blood umbilical Vein – foramina and ducts bypass lungs (collapsed)
- Umbilical vein to IVC – ductus venous – ligamentum venosum (posterior liver separates caudate lobe from left lobe)
- RA to LA – foramen ovale – fossa ovalis (shuts due to pressure change)
- Pulmonary trunk to aorta – ductus arterious (constricts response to high O2)– ligamentum arteriosum
Right to left shunts:
Right to left shunts – early cyanosis (5 Ts)
Transposition – not compatible with life without shunt
Tetraology of fallot
Pulmonary stenosis (R->L flow)
R vent hypertrophy (boot shaped heart)
Overiding aorta
VSD
Left to right shunts:
– late cyanosis (don’t present as baby)
VSD
ASD
Patent ductus arteriousus
Eisenmenger syndrome
HI
Analyse chest CT
Axial CT remember:
You are looking up from the feet of the patient.
- Vertebrae posterior
Region of body? - Thorax
Is there contrast? - look for differences in brightness between arterial and venous system
Arterial vs venous phases
Lung window
Image type, section, contrast?
Eg. CT Axial with contrast
HI
Analyse chest X-ray
Yr 2, notes, exam
- PA film is standard and will be unlabelled
- Patient is standing looking toward you
- AP film will be labelled
- Heart should not be more than ½ width on PA film
- Airway
- Look at the trachea and its branches to make sure the airway is patent and midline. Narrowing of the airways can indicate edema or stenosis. In a tension pneumothorax, the airway will be deviated away from the affected side. Note that in kids, the airway should be straight. In adults, it can be deviated to the right due to the aortic arch.
- Bones and Breast Shadows
- Check the bones including the clavicles, ribs, scapulae, thoracic vertebrae and humeri looking at size, shape, shadows and boarders. Remember, don’t miss the bony structures outside the chest as these are often visible in the X-ray. Examen the bony structures for fractures, lytic lesions (darker areas or changes in bone density), and deformities. At the joints, look at joint spaces for narrowing, widening, and air in the joint space.
- Cardiac Silhouette and Costophrenic Angles
- The cardiac silhouette is the white space on the X-ray representing the heart. Normal heart size is half of the chest width. Most computerized X-ray viewing program have an easy to use measuring tool that can quickly help you determine if the heart is enlarged, known as cardiomegaly. Examen the shape of the heart. A water-bottle-shaped heart can be indicative of pericardial effusion. Note the location of the heart, which side is it on? The boarders around the heart should be clear. An undefined right boarder suggests middle lobe lung consolidation and a poorly defined left boarder suggests lingular lung consolidation.
- Check the costophrenic angles, where the diaphragm and chest wall meet. The angle should be well defined. Whiteness or poorly defined angles can be a sign of pleural effusion or consolidation.
- Mention 8 cardiomediastinal contours here:
1. right paratracheal stripe
2. right heart border
3. right hemidiaphragm
4. left hemidiaphragm
5. left heart border
6. aortic knuckle
7. main pulmonary artery
8. descending aorta - Diaphragm
- The outline of the diaphragm should be smooth and the right ride of the diaphragm higher than the left. The highest point of the left diaphragm should be just lateral to the middle of the lung and the highest point on the right in the middle of the right lung. Deviation to one side or the other can signal pneumothorax. Look for air below the diaphragm which may indicate bowel perforation.
- Extrathoracic Tissues
- Examen the soft tissues for abnormalities, specifically lymph nodes and subcutaneous emphysema (air below the skin), as well as any other lesions.
- Fields
- Dividing the lungs into sections, upper, middle, and lower, and begin to examen the lungs themselves. Look for symmetry between the lungs. Fluid, such as blood, mucus, or tumor, are radiodense making the area appear white. Air filling appears black on the X-ray. As you examen the lungs, check for areas of opacity or patchy shadows, examen the vasculature and look for areas of consolidation. Also, look for Kerley lines, thin linear opacities that signal pulmonary edema and suggest congestive heart failure.
- Gastric Fundus
- Just below the heart, you should note the presence of a gastric bubble. Assess the amount of gas present.
- Hilum and Mediastinum
- Look at the hilum, the area of the lung containing the pulmonary arteries and main bronchus. The left lung hilum should be slightly higher than the right. Specifically, check for any visible lymph nodes. Calcified lymph nodes can be a sign of prior tuberculosis infection.
- Instrumentation
- Are there any tubes, IV lines, EKG leads, surgical drains, or a pacemaker present on the X-ray? If so, are they properly positioned? Make note of these in your report.
Describe the hierarchy of pacemaker cells and correlation with ECG
A note on impulse conducting system cells (ICS):
- it is modified cardiac muscle
- has fewer striations that other cardiac myocytes (thus its contractions are weaker)
- it is also has fewer mitochondria (as they are not ‘contracting’ muscle cells)
- Purkinje cells are a “highway”: they conduct easily (“speed up transmission to ventricles”) as they have more gap junctions compared to ventricular cells (which are adapted for contraction)
- Sinoatrial and Atrioventricular (SA and AV)^[“safety valves”] nodal cells are smaller, and conduct less easily (due to high internal resistance, and fewer gap junctions–resulting in poorer, slower conductance)
Macroscopic specialisations
The cells of the heart are responsible for propagating a signal across the heart.
All heart cells can spontaneously depolarise.
However, there is a hierarchy of depolarisation of the cardiac cells.
- The sinoatrial (SA) node is the pacemaker
- Depolarisation starts in the SA node in the right atrium
- This ‘wave’ (depolarisation) spreads through the atria at a speed of about 100 ms and is funnelled into…
- The Atrioventricular (AV) node, which is located in the interatrial septum, with a 160 ms delay - this conduction delay is due to annulus fibrosis, allows for ventricular filling time
- The wave then travels down from the septum into the apex
- It spreads down the His bundle, into the right and left bundles
- It then spreads out widely, into the Purkinje fibres in the ventricles
- The Purkinje fibres propagate the depolarisation to all of the ventricular myocardium (this occurs very quickly, about 80-100 ms from AVN to all ventricles)
A “mexican wave” propagating across the heart from top to bottom.
The direction of the wave in myocardium is:
- septum –> apex —> back to AV groove
- from endocardium —> epicardium
ECG correlates:
- P wave: atrial depol
- QRS complex: ventricular depol
- T wave: vent repol
Beats:
- SA node: 60-100 bpm – sinus rhythm
- AV node: 40-60 bpm
- Purkinje: 20-40 bpm
NB. under normal physiologic conditions, the depolarisation wave CANNOT re-enter the AV node, and can’t pass the fibrous AV barrier
- # clinicallyrelevant examples of when this DOES occur:
- circuitous rhythm
- Wolf-Parkinson-White : AV septum allows propagation of signals too quickly, thus it preferentially reaches ventricles before it is meant to, resulting in arrhythmia.
HI
What formula explains the relationship between heart rate, stroke volume and cardiac output?
CO = HRx SV
Can be corrected for body surface area by dividing e.g. by 1.73 m2
Producing CI
Cardiac Output (ml/min) = Heart Rate (beat/min) x Stroke Volume (ml/beat)
CO = HR x (End Diastolic Volume – End Systolic Volume)
HI
How do you calculate Ejection Fraction?
Ejection Fraction = SV / EDV = (EDV – ESV)/EDV
HI
What formula explains the relationship between Blood Pressure, Cardiac Output and Total Peripheral Resistance (TPR = systemic vascular resistance)?
Mean Arterial Pressure = Cardiac output x total peripheral resistance
HI
What is the formula for pulse pressure and what is its importance?
Pulse Pressure = Systolic Blood Pressure – Diastolic Blood Pressure
** Pulse pressure will be important to understand when we cover myocardial oxygen supply and PV loop pathology.
**
In valve diseases you can have pulse pressure changes which are palpable:
Aortic regurgitation: collapsing pulse
HI
What are the determinants of myocardial oxygen demand?
Yr 2, and own notes
↑ Contractility
- Increased Ca2+ Influx 🡪 Increased active/secondary active transport to move Ca2+ out of cell 🡪 Increased energy use 🡪 increased O2 demand
- Beta blockers (reduce HR and contractility) and Digoxin (inhibit Na+/k+ pumps reduce active transport) to reduce Oxygen Demand
↑ Afterload
- Often thought about as pressure the heart must overcome to eject blood from the heart (i.e. Aortic Pressure or Mean Arterial Pressure) (Easier to understand ☺)
- Better thought about as Ventricular Wall Stress (but more complicated ☹)
- Ventricular Wall Stress = Wall Tension / Wall Thickness = (Pressure x Radius) / Wall Thickness.
- Important as an over worked heart will increase wall thickness to reduces ventricular wall stress as a means of reducing after load and myocardial oxygen demand!
- Medications can reduce after load (all hypertensive medications: Beta blockers, calcium channel blockers, ace inhibitors, etc.)
↑ Heart Rate
- Increased HR 🡪 Reduced time spent in diastole 🡪 Reduced filling time 🡪 Reduced pre-load 🡪 internal work increases (more isovolumetric contractions) 🡪 Less efficient PV loop.
- Beta Blockers to reduce Oxygen Demand by decreasing HR
↑ Diameter of the Ventricle (Preload)
- Increase preload 🡪 increased diameter of the ventricle 🡪 Increase wall tension 🡪 Increased energy requirement
- Important as any heart related condition which increases pre-load (i.e. valve regurgitation, heart failure etc) will increase myocardial oxygen demand!
- Diuretics and nitroglycerin reduce pre-load
HI
What are the determinants of myocardial oxygen supply?
Yr2, exams and own notes
What Formula Describes Oxygen Delivery to the body?
= Cardiac output x Arterial Oxygen Content
= HR x SV x (([Hb] x 1.39 x SaO2) + 0.003 pO2)
What is the Coronary Perfusion Pressure?
- Coronary Perfusion Pressure (CPP) = Aortic Diastolic Pressure – Left Ventricular end-diastolic Pressure (LVEDP)
- Conditions with lower Aortic Diastolic Pressure (e.g., aortic regurgitation) or higher LVEDP (e.g., Diastolic Heart Failure) have reduced oxygen supply.
- Conditions which increase LV pressure and Lower Aortic Pressure (i.e. Aortic Stenosis) or lower Distal Coronary Artery Pressure (i.e. coronary artery disease) have reduced oxygen supply
When do the Left and Right Ventricles Receive most of their blood supply?
- Left: Ventricular Diastole (especially isovolumetric relaxation/early diastole)
- Right: Predominantly in ventricular systole but occurs through both ventricular systole and diastole (Because right ventricular pressure is low!).
How does Heart Rate affect Myocardial Oxygen Supply?
Increased heart rate 🡪 decreased diastole 🡪 less Left Ventricular Oxygen supply (and higher oxygen demand)
- CBF = CPP/CVR
- CPP = Aortic root pressure – Ventricular pressure
- CPP dependent on the phase of the cardiac cycle
- LV Flow predominately in diastole
- RV flow predominately in systole - CVR determined by the radius of the vessel wall
- Metabolic control main mechanism – increased radius with increased O2 demand
- Myogenic autoregulation
- Neural and humoral control of smaller importance
Arterial oxygen content measures the amount of oxygen that is actually in the blood. It is dependent on three factors:
- amount of haemoglobin (g/L)
- degree of oxygen saturation of haemoglobin molecule (%)
- amount dissolved in plasma
Oxygen carrying capacity of haemoglobin
If haemoglobin is 100% saturated with oxygen, and 1 g of haemoglobin can carry 1.39 ml of oxygen, and there is 150 g Hb/L of blood then there is 208.5 mls of 02 per litere of blood.
Note that the amount of haemoglobin in the blood is the biggest determining factor in this equation. If there is half the usual amount of haemoglobin int he blood then there will be half the amount of oxygen in the blood.
note: typically the haemoglobin is not 100% saturated with oxygen, healthy lower limit is around 88-90%.
Therefore the amount carried by Hb should be calculated as:
Hb (g/L) * 1.39 * % saturated
Note also: the degree of saturation of haemoglobin is dependent upon the partial pressure of oxygen in the plasma. This can be represented in the oxygen dissociation curve. Notice also that at 90% saturation, this is just before the drop-off of partial pressure and oxygen saturation.
The lower the partial pressure of oxygen in the plasma, the lower the oxygen saturation of haemoglobin.
The final formula for arterial oxygen content is then:
([Hb] * 1.39 * SaO2) + 0.003P02
Note that pO2 makes a relatively tiny contribution to the arterial oxygen content, largely driven by Hb and its oxygen carryign capacity.
Cardiac output (L/min)
Cardiac output is dependent on stroke volume (ml, how much goes out with every beat) and heart rate (bpm).
The stroke volume depends on the sarcomere length (see [[Histology Lecture 5]], [[Cell Biology Lecture 3]]) at the end of diastole, as heart relaxes and stretches. Thus the heart must be filled up properly ^[note that the heart can stretch too much, and is ineffective]
Starling’s curve:¬
‘The larger the volume of the heart, the greater the energy of its contraction’
‘It is the volume (not pressure) at the beginning of contraction which determines the amount of energy set free during the contraction’
‘Energy of the contraction is a function of he length of the muscle fibre; increasing eh active surfaces by stretching a muscle also increases its force of contraction’¬¬
HI
Describe the phases of the cardiac cycle
Yr2, own notes, exams (>3)
The cardiac cycle is The sequence of events in one heart beat. It comprises electrical and mechanical events.
Electrical events can be precisely determined using an ECG:
- P waves correspond to atrial depolarisation
- QRS complex corressponds to ventricular depolarisation, and the start of systole
(ST— plateau, calcium influx, intiiates contraction of ventricular muscles)
- t wave: corresponds to ventricular repolarisation – links to end of plateau phase in cardiac AP, start of relexation/end of systole
Mechanical events:
- functionally the heart can be thought of as two, left and right, serial pumps, connected by high and then low pressure vascular beds e.g. high pressure in RV–> low pressure in pulmonary artery; left artery–> left ventricle (high pressure)–> aorta
- contraction leads to increase in pressure and flow of blood out of chamber and therefore decrease in chamber volume
- thus failing of one part draimatically imposes load on preceding elements because the chambers are set up as a series (e.g. failture of LV to pump creates build up in LA, pulmonary circulation etc - i.e. continuous)
The heart sounds S1 and S2 delimit systole and diastole
- valve closure produces audiable sounds
- the closure of AV valves produces S1
- the closure of semilunar valves produces S2
- systole occurs between S1-S2, where ventricles contract, push blood into vessels until valve closure
- diastole occurs between S2 and S1 –> ventricular filling
Atrial Contraction
Isovolumetric Contraction
Rapid Ejection
Reduced Ejection
Isovolumetric Relaxation
Rapid Filling
Reduced Filling (Diastasis)
Phases 1, 5, 6 and 7 are part of ventricular (LV) diastole.
Phases 2, 3, and 4 are part of ventricular systole.
Atrial contraction: - atrial depolarisation leads to atrial contraction/systole - this build up of pressure in the atrium creates a gradient that enables blood flow into the ventricle - at the end: peak EDV of ventricles - note: atrial kick– accounts for 5-15% of filling of ventricles, explains why people with atrial fibrillation may present as haemodynamically stable Isovolumetric contraction: - early stage of ventricular systole- demarcated by S1 i.e. closure of av valves, as atrial pressure dips below ventricular pressure - ventricular depolarisation - QRS - at the beginning, there is Pa=0mmHg in the ventricle - it must build up force i.e. tension in order to overcome pressure in aorta and eject blood - at this stage, there is no flow of blood, as semilunar valves are still closed - as pressure builds up, and overcomes aortic pressure, semilunar valves open (on graph, curve of ventricular pressure exceeds aortic at 120 mmHg), pressure continues to increase and then peaks leading to ejection Rapid ejection - due to great pressure difference between ventricles and aorta - functionally, ventricles and aorta compose one continguous chamber in this phase - pressure decreases as blood is ejected - volume expelled = stroke volume Reduced ejection - pressure gradient has decreased, blood continues to flow due to mometum from early stage systole - repolarisation - beginning of relaxation i.e. diastole - demarcated by S2, closure of semilunar valves - some volume remains – end systolic volume - stroke volume = EDV- ESV - n.b. ejection fraction (different) = SV/EDV, measured by echo to get picture of heart function ^[Doppler?] ^[usually 70%, can vary based on age and body size, other factors]
Note: as aorta is elastic, some backflow as valve shuts (seen as dicrotic*)
Isovolumetric relaxation - early diastole - all valves are closed - aim is to return pressure in ventricles back to zero to prepare for filling and 7. Rapid and reduced filling - i.e. late diastole - atrioventricular valves open (as pressure in ventrucle dips below that of atria) - filling occurs by passive flow because of pressure gradient, intially quickly i.e steep gradient on volume graph, then slows, can also see atrial kick on plot - reduced filling: smaller pressure gradient
Note: aortic pressure varies between 80-120, 120 -systolic, 80-diastolic
atrium fluctuates within range of 0-40mmHg
note: atrial kick– accounts for 5-15% of filling of ventricles, explains why people with atrial fibrillation may present as haemodynamically stable
HI
Relate the cardiac cycle to PV loop
Yr 2, own notes, exams
recognise changes in pathology
HI
What changes to PV loop occur in valvular disease?
Yr 2, own notes, exams
HI
Describe changes that occur in heart failure to PV loops
Yr 2, own notes, exams
HI
Describe how blood pressure is regulated
Yr 2, own notes, exams
Baroreceptors
- low perfusion pressure leads to ischaemia
- high pressure leads to tissue injury e.g. haemorrhagic stoke
- therefore need rapid negative feedback regulation
- the variable is BP
- sensor are baroreceptors/mechanoceptors
- integrator is central controller aka medulla oblongata and hypothalamus (note baseline is SNS tone, PSNS is quiescent)
- effector: SNS and PSNS efferent activity, affecting function of heart, respiratory system, vessels, kidney and muscles
- two types:
- high-pressure arterial baroreceptors, within carotid sinuses and aortic arch
- carotid sinus CNIX, aortic CNX (less sensitive) send information to solitary tract on nucleus
- negative feedback via rostral ventrolateral medulla results in decreased sns input, with negative chronotropic, inotropy, stroke volume, and decreased svr and vr (note: that RAAS is upregulated)
- positive feedback via vagal nucleus and nucleus ambiguus results in increased PSNS with negative chronotropic and inotropic effects and decreased SV
- note that low BP or PP reduces afferent firing
- response is usually between 60-180 mmHg AND MOST SENSITIVE at 90 mmHg
- firing rate set point increases with chronic hypertension
- clinically tested with valsalva manoeuvre
- low-pressure volume receptors, within atria, ventricles and pulmonary vasculature
- cardiopulmonary
- detect changes in vlood volume which affects vessel stretch
- in RA, VC and pulmonary veins, communicate via CNX to medulla
- two types of fibres
- triggers Bainbidge reflex decreased venous return leading to decreased heart rate via the effects of ANS on SAN
- hypothalamus decreases thirst and ADH secretion leading to increased water excretion and natriuresis
- Bezold Jarisch reflex” decreased venous return resulting n bradycardia and apnoea
- long term equilibration of blood volume
- baroreceptors are free nerve endings that act as mechanoceptors-
- vessel stretch or pressure inhibits potassium channels, leading to depolarisation and action potential generated
- the response is relative to degree of stretch and rate of change in stretch
Baroreceptor Reflex
- Stimulus: increased blood pressure and stretch, or decreased blood pressure and stretch
- Afferent pathway: from carotid sinus or aortic arch, via carotid sinus nerve (CNIX) or aortic nerve (CNX). Both nerves travel through the jugular foramen to enter the medulla
- Solitary tract nucleus receives afferent fibres and redistributes the signal into several efferent regulatory system
- Efferent pathways include parasympathetic and sympathetic nerve fibres, to heart (modulating heart rate via cardiac ganglion), and to heart, peripheral resistance vessels and adrenal medulla (indirectly influencing blood pressure via release of epinephrine and norepinephrine)
Note increased sympathetic and decreased vagal activity is a result of low baroreceptor firing, which increases CO and SVR to increases arterial pressuer.
HI
Describe the action potential in pacemaker cells and how it is therapeutically targeted
Yr 2, own notes, exams
Describe the phases of the pacemaker cell Action Potential:
Phase 0: Voltage Gaited Ca2+ Channels open, Ca2+ influx into cell.
Phase 3: Repolarization – inactivation of Ca2+ channels, increased activation of K+ channels 🡪 K+ efflux.
Phase 4: Pacemaker (funny) current: influx of Na+ resulting in slow depolarizing potential.
No plateau, no spike
Why is knowing this important:
Ca2+ Channel blockers slow phase 0
Beta blockers used to slow Pacemaker current to slow heart rate.
Medications (e.g. Ivabradine) can be used to slow the Pacemaker current and slow heart rate
How can the Pacemaker potential rate change?
Sympathetic Stimulation / Epinephrine and Norepinephrine: Increase rate of pacemaker potential 🡪 faster depolarization 🡪 higher heart rate
Parasympathetic Stimulation: Decreased rate of pacemaker potential 🡪 Slower depolarization 🡪 Slower heart rate.
Why is knowing this important:
Any conditions or medications which increase sympathetic activity (e.g. shock, blood loss, infection, hyperthyroid disease (up-regulation of adrenergic receptors), etc) or reduces parasympathetic activity (muscarinic antagonists) can result in tachycardia.
Any condition or medication which increases parasympathetic activity (muscarinic agonists) or reduces sympathetic activity can result in bradycardia.
Which structures of the conducting system are self excitable?
What is their rate of discharge?
SA Node ~ 60-100 bpm
AV Node ~ 40-60 bpm
Purkinje Fibers ~ 20-40 bpm
Why is knowing this important:
Normal Sinus Rhythm or Sinus Arrythmia should have a rate of >60 BPM
When AV Node or Purkinje fibers take over it generally results in bradycardia
Describe the action potential in cardiac muscle cells and their clinical relevance
Yr 2, own notes, exams
Describe the phases of the cardiac muscle cell action potential:
Phase 0: Rapid depolarization: Fast Na+ channels open
Phase 1: Early repolarization: efflux of K+
Phase 2: Plateau: influx of Ca+, Efflux of K+
Phase 3: Repolarization: Efflux of K+
Phase 4: Resting membrane potential
Why is knowing this important:
Sodium Channel Blockers: slow the influx of Na+
Potassium Channel Blockers: Delay phase 3 increasing AP duration
Early After Depolarizations (EADs) can occur during the relative refractory period (phase 3) of the cardiac muscle cell AP and result in ventricular fibrillation.
Delayed After Depolarizations (DADs) can occur during phase 4 resulting in ventricular fibrillation.
Note also Refractory periods, add in channels
HI
Describe myocardial ischemia
Own notes and exams
Failure of oxygen and substrate delivery
to meet the metabolic demands of the
myocardium
- Imbalance of supply and demand
- Coronary vascular disease the most common cause of ischaemia
- Vessel narrowing leads to reduction in CBF leading to ischaemia and the classical symptoms of angina
Cellular effects are complex and are due to both the initial effects of ischaemia and reperfusion
- The degree of injury is dependent on the duration and severity of ischaemia
HI
What are the determinants of oxygen delivery?
own notes and Y2 notes
¬¬ The formula for oxygen delivery is = cardiac output (L/min)** arterial oxygen content (ml/min)
O2 delivery can be simply described by CO * AOC
Myocardial oxygen supply is the product of arterial oxygen carrying capacity and coronary blood flow
- DO2 = (Hb x 1.34 x SaO2) + (PaO2 x 0.003)
- CBF = CPP/CVR (in case of brain, heart)
- CPP = Aortic root pressure – Ventricular pressure (aortic diastolic pressure - LVEDP)
- CPP dependent on the phase of the cardiac cycle
- LV Flow predominately in diastole
- RV flow predominately in systole
- CVR determined by the radius of the vessel wall
- Metabolic control main mechanism – increased radius with increased O2 demand
- Myogenic autoregulation
- Neural and humoral control of smaller importance
Arterial oxygen content measures the amount of oxygen that is actually in the blood. It is dependent on three factors:
- amount of haemoglobin (g/L)
- degree of oxygen saturation of haemoglobin molecule (%)
- amount dissolved in plasma
Oxygen carrying capacity of haemoglobin
If haemoglobin is 100% saturated with oxygen, and 1 g of haemoglobin can carry 1.39 ml of oxygen, and there is 150 g Hb/L of blood then there is 208.5 mls of 02 per litere of blood.
Note that the amount of haemoglobin in the blood is the biggest determining factor in this equation. If there is half the usual amount of haemoglobin int he blood then there will be half the amount of oxygen in the blood.
note: typically the haemoglobin is not 100% saturated with oxygen, healthy lower limit is around 88-90%.
Therefore the amount carried by Hb should be calculated as:
Hb (g/L) * 1.39 * % saturated
Note also: the degree of saturation of haemoglobin is dependent upon the partial pressure of oxygen in the plasma. This can be represented in the oxygen dissociation curve. Notice also that at 90% saturation, this is just before the drop-off of partial pressure and oxygen saturation.
The lower the partial pressure of oxygen in the plasma, the lower the oxygen saturation of haemoglobin.
The final formula for arterial oxygen content is then:
([Hb] * 1.39 * SaO2) + 0.003P02
Note that pO2 makes a relatively tiny contribution to the arterial oxygen content, largely driven by Hb and its oxygen carryign capacity.
Cardiac output (L/min)
Cardiac output is dependent on stroke volume (ml, how much goes out with every beat) and heart rate (bpm).
The stroke volume depends on the sarcomere length (see [[Histology Lecture 5]], [[Cell Biology Lecture 3]]) at the end of diastole, as heart relaxes and stretches. Thus the heart must be filled up properly ^[note that the heart can stretch too much, and is ineffective]
Conditions with low aortic diastolic pressure e.g. aortic regurgitation, higher LVEDP (diastolic heart failure) have reduced oxygen supply.
Conditions with increase LB pessure and lower aortic pressuer (aortic stenosis) OR lower distal coronary artery pressure (i.e. CAD) have reduced oxygen delivery
Starling’s curve:¬
‘The larger the volume of the heart, the greater the energy of its contraction’
‘It is the volume (not pressure) at the beginning of contraction which determines the amount of energy set free during the contraction’
‘Energy of the contraction is a function of he length of the muscle fibre; increasing eh active surfaces by stretching a muscle also increases its force of contraction’¬¬
HI
Describe ACEi and ARBs, mechanism of action, adverse effects, indications and contraindications
exam,
- ACEIs: - Stop the renin-angiotensin pathway by inhibiting the conversion of angiotensin I (no appreciable activity) to angiotensin II (potent vasoconstrictor) - Inhibit vascular tone - directly lower BP - Inhibit aldosterone release - indirectly lower BP
Indications:
- hypertension
- HFrEF - 1st line treatment
- AF
- ACS: especially fo coinicdent indications e.g. hypertension, CKD, T2D
- LV dysfunction
Adverse effects:
- cough
- angioedema
- hypotension
- dizziness (postural)
- hyperkalaemia
- taste
- allergy
- reanal impairment (RA stenosis)
PK:
- oral absorption
- t1/2 10
Contas:
- Triple whammy
- pregnancy
- RAS especially bilaterally
- hisstory of angioedema
-
AngII receptor antagonists (sartans) - Drugs that bind at the AT1 receptor to block action
- - decreased vasoconstriction, increased salt excretion
- - More direct as drug target so limited effect on serum K+
- - No effect on bradykinin metabolism
- n.b. The ‘triple whammy’ of ACEI, NSAID, diuretics…leading to reduced renal perfusion and acute kidney injury (AKI).
- Increased concentrations of cytosolic calcium cause increased contraction in both cardiac and smooth muscle cells (↑ calcium = ↑ contractions = ↑ BP)
-
Indication:
- hypertension (most prescribed)
- LV dysfunction
- systolic heart failure
Pharmacokinetics:
- good oral absorption
- half life ~ 8-10 hours
- cleared by hepatic metabolism
Adverse effects:
- increased serum K
- less cough and angioedema
- - hypotension
- allergy
- renal impairment
Contras:
- pregnancy
- bilateral
- K sparing e.g. MRA and ENAC
Advantages and disadvantages of ACEI/ARB
- Recommended as first-line treatment of hypertension, especially those with DM, heart failure, CVD/IHD, or proteinuric chronic kidney disease
- No rebound hypertension
- Long-term benefits on cardiac remodelling and kidney disease with proteinuria
-
##### Valsartan with sacubitril (entresto)
This is a fixed dose combination, indicated for heart failure with reduced ejection fraction as a replacement for ACEI or ARB.
HI
Describe CCBs, mechanism of action, adverse effects, indications and contraindications
exams and own notes
- Blocking inward movement of calcium through the slow channels of the cell membrane of cardiac and smooth muscle cells (L-type, alpha)
- Activity varies depending on the type of cardiovascular cells involved:
- Myocardium
- Cardiac Conduction System (SA and AV nodes) - slow conduction
- Vascular Smooth Muscle
- ↓ BP by ↓PVR
Indications: hypertension, HR control in AF/NCT, ACS symptoms and ischaemia reduction (Coronary vasodulation - alt to BB)
- Two main classes of CCB’s: non-DHPs and DHPs
- Non-dihydropyridines (target vascular and myocardial cells): vasodilation, and negative ionotropic and chronotropic effects
- diltiazem
- effects:
- Targets peripheral blood vessels and cardiac calcium channels,
*Less effect on the heart compared to verapamil,
*↓ HR and mean arterial BP
- -DRUG INTERACTIONS (CYP inhibitor)
- verapamil (used as anti-arrhythmic)
- effects: targets primarily cardiac calcium channels, strong cardiac depressant effect: decreased heart rate and CO, reduces AV conduction and blocks SA node, decreased PVR and BP
- drug interactions: CYP inhibitor, can increase digoxin concentration
side effects of non-DHPs: bradycardia, constipation, AV block, worsening heart failure
Dihydropyridines (target peripheral vascular smooth muscle) - central and peripheral effects
* - amlodipine, nifedipine, felodipine
* - effects:
*More selective as vasodilators and have less cardiac depressant effects (less effect on heart rate)
*Produce reflex tachycardia by indirectly increasing sympathetic tone
*Primarily work on vascular smooth muscle to reduce PVR,
*Increased incidence of peripheral oedema
* - side effects: Peripheral oedema (non-responsive to diuretics), Hypotension, Reflex tachycardia and chest pain, flushing, palpitations
Describe the use of adrenaline, MoA, adverse effects, indications and contraindications
Released as a result of sympathetic stimulation
- Non-selective agonist for all alpha and beta receptors (choice and degree of activity is dose dependent)
- Activity is related to which receptor is being agonised.
- As alpha agonist can cause vasoconstriction (vascular smooth muscle contraction)
- As beta agonist can increase chronotropy (rate of cardiac contraction) and inotropy (force of contraction) and can be used for low cardiac output (i.e. decompensated cardiac failure)
- Mechanism of Action: Naturally occurring chemical that stimulates sympathetic receptors (receptor activation is dose dependent).
- Effect:
- Low doses: Increased heart rate (chronotropy) and force (inotropy) via beta receptors.
- Higher doses: Vasoconstriction and has ‘less cardiac actions’ via alpha receptors.
- Indications: Can be given as a bolus dose or infusion (bolus for cardiac arrest and intramuscular for anaphylaxis).
- Alpha 1:
- Expressed in blood vessels, gut and skin
- Improves perfusion
- Agonists indicated Hypotension, Nasal congestion (phenylephrine and pseudoephedrine, acting locally), Glaucoma
- Agonists mimic the SNS response
- (Agonists: Noradrenaline, Oxymetazoline, Phenylephrine, Pseudoephedrine;
- Antagonists: Prazosin, Tamsulosin, Phenoxybenzamine, Phentolamine)
- Antagonists e.g. prazosin indicated in BPH and HTN
- Alpha 2:
- a dilator
- mediates NA release, prevents an “over-reaction”
- located in pre-synaptic terminals of the CNS
- In ICU setting: Hypertension, Analgesia, sedation, agitation and others
- (Agonists: Clonidine, Dexmedetomidine, Brimonidine aka the “idines”)
- No clinically relevant antagonists
- Note: agonists are not really used clinically
- Note 2: glaucoma and eyedrops
- Alpha 1:
Beta Receptors
- Beta 1:
- has positive chronotropic and inotropic effects
- ensures good perfusion
- expressed in heart
- Indicated in heart failure, Bradycardia
- (Agonists: Dobutamine, Adrenaline; Antagonists: Metoprolol, Atenolol)
- Agonists are fairly selective
- Note: dosage of adrenaline is inversely realted to selectivity
- Antagonists are cardioselective, and include metoprolol and atenolol, indicated for heart failure, tachyarrhythmias and hypertension ^[can use for HF when stable]
- Beta 2:
- similar to alpha-2, a dilator
- relaxant
- located in lungs
- Asthma
- (Agonists: Salbutamol (inhaled, Terbutaline)
- Agonists result in bronchoconstriction
- Non-selective antagonists, and vary in their selcectivity e.g. propranolol used in hypertension, tacharrhythmias, and migraines
- Care must be taken in prescribing if patient has asthma and COPD to prevent bronchospasm
HI
Describe the use of beta blockers
exams and own notes
note a 3.5
DBeta blockers: Mechanism of action:
- Competitively block beta receptors in heart, peripheral vasculature, bronchi, pancreas, uterus, kidney, brain and liver.
- Beta-blockers reduce heart rate, BP and cardiac contractility; also depress sinus node rate and slow conduction through the atrioventricular (AV) node, and prolong atrial refractory periods.
- The affinity of individual beta-blockers for beta receptors varies (B1, B2 and B3)
- Beta 1 selective (eg metoprolol, bisoprolol, nebivolol)
- Beta non-selective (eg propranolol)
- Some beta blockers also have alpha blockade (carvediolol and labetalol)
- Some have anti-arrythmic effects through additional potassium channel blockade (eg sotolol)
Indications:
- Myocardial infarction
- Tachyarrhythmias
- Angina
- Chronic heart failure with reduced ejection fraction as part of standard treatment (eg with ACE inhibitor, diuretics)
- Hypertension (not first line)
- Prevention of migraine
- Topical application (eye drops) for glaucoma (eg timolol)
Precautions:
- Consideration of risk v benefit is very important when considering beta blocker treatment.
- Contraindicated in bradycardia (45–50 beats/minute), second‑ or third-degree AV block, sick sinus syndrome, severe hypotension or uncontrolled heart failure. Beta-blockers may worsen first-degree AV block
- Asthma: Caution in severe or poorly controlled asthma as they may precipitate bronchospasm. Beta1-selective beta-blockers are preferred for patients with well-controlled asthma (on specialist advice).
- Treatment with drugs that cause bradycardia may further decrease heart rate and cause heart block and hypotension; avoid combination with verapamil (cardioselective CCB)
Side-effects
- cardiovascular: Decreased HR, hypotension, transient worsening of heart failure
- peripheral: cold extremities, exacerbation of Raynaud’s phenomenon
- respiratory: Bronchospasm, dyspnoea
- neurological or endocrine: Depression, fatigue, dizziness, altered glucose and lipid metabolism
LOW
Describe the use of noradrenaline
Noradrenaline
- Mechanism of Action: Naturally occurring chemical that stimulates sympathetic system receptors (alpha).
- Note: cannot be administered peripherally, otherwise constriction of peripheral vessels and death of tissue
- Effect: Vasoconstriction, no effect on heart rate or force of contraction (has very little activity on beta receptors).
- Indications: Used to increase blood pressure., in hypotensive states e.g. vasodilatory shock
- Administration: Only to be administered by infusion (i.e., not for bolus dosing) via a CVC.
HI (also kidney)
Describe diuretics - mannitol
exams and own notes
Mechanism of action of osmotic diuretics
- Mannitol, sorbitol, urea
- Given via infusion (mannitol) with fast action
### Rationale of use - Site of action: proximal tubule (PT) and thick ascending limb (TAL)
- Substances bind water in the tubule, recruiting water from ICF
- Impacts urine concentration and water resorption
Indications and Contraindications; Adverse effects
- Indications (hospital setting - ICU): brain oedema, forced diuresis, impending anuria
- Adverse effects: paracellular transport ↓ causing Mg2+ loss
- Contraindications: heart failure, persisting oliguria/anuria
HI
Describe diuretics - CAH
exams and own notes
Mechanism of action of inhibition of CAH
- Actions in various locations
Mechanism of CAH Inhibitors
- Site of action: 1st PT / 2nd CD
- Acetazolamide blocks CAH immediately
- Loss of HCO3- leads to metabolic acidosis
### Rationale of use
### Indications and contraindications; Adverse effects
Clinical Use of CAH Inhibitors
- Indications: open angle glaucoma, edema
- Adverse effects: metabolic acidosis
- Contraindications: acidosis
HI
Describe diuretics - Loop diuretics and thiazides
exams and own notes
Mechanism of action of loop diuretics
- Site of action: ascending loop of Henle
- Very potent diuresis with fast action
Mechanism of Loop Diuretics
- Site of action: ascending loop of Henle (TAL)
- Block Na+/K+/2Cl–symporter, leading to significant Na+ reabsorption blockade
- Paracellular diffusion decreases
### Rationale of use
### Indications and contraindications; Adverse effects
- Indications: edema, forced diuresis, impending anuria
- Adverse effects: loss of electrolytes, uric acid excretion changes
- Contraindications: coma hepaticum, anuria
Mechanism of action of thiazides and analogues
- Old substance group, competition for Cl–binding site on Na/Cl-symporter
- Good oral absorption, high protein binding
Mechanism of Thiazide Diuretics
- Site of Action: Distal Tubule (DT).
- Competition for Cl–Binding Site: Na/Cl-symporter.
- Excretion of K+ and H+: Due to [Na+] ↑ (Load-dependency of Na+ resorption).
- No TGF Effect: Action after macula.
- Moderate Efficacy: 5% of Na+ load.
- Physiological Impact: Quite “physiological”.
- Weak CAH Inhibition: Some thiazides weakly inhibit CAH.
Rationale of use
### Indications and contraindications; Adverse effects
- Indications:
- Oedemas with good GFR
- Hypertension
- prevention of kidney stoens in hypercaclaemia
- Side Effects:
- Loss of K+
- Retention of uric acid (gout)
- Haemoconcentration (thrombosis, haematocrit)
- Reduced glucose tolerance
- Contraindications:
- Sulphonamide hypersensitivity
- Hypokalemia
- Anuria
HI
Describe diuretics - ENaC
exams and own notes
Mechanism of action of ENaC
- Oral Absorption for Amiloride: 15 - 25%.
- Kinetic Properties: τ1/2 = 21 h (daily dose).
- Action Beyond Kidney: Also in skin, rectum, etc. where ENaC channels are expressed.
- Small Diuretic Effect: Only 2% of Na+ load.
Mechanism of Inhibitors of ENaC
- Site of Action: Distal Tubule (DT) / Collecting Duct (CD).
- Filtered and Secreted in PT: Via organic anion secretion mechanism.
- Blocking Action from Luminal Side: Na+-resorption↓ → small volume loss.
- No Effect on Renal Hemodynamics: After macula densa.
- Amiloride’s Other Effects: High doses can block other transporters.
Rationale of use
### Indications and contraindications; Adverse effects
- Indications:
- Hypertension (in combination with other diuretics).
- Adverse Effects:
- Volume contraction → uric acid reabsorption↑ in proximal tubule.
- Nausea, vomiting, diarrhea.
- Contraindications:
- Hyperkalemia
- Anuria
K sparing - issue with ARBs - incraese chance of serum yperhalaemia
Describe diuretics - MC receptor antagonists
Mechanism of action of MC receptor antagonists
- Oral Absorption of Spironolactone: 60 - 70%.
- Kinetic Properties: τ1/2 = 1.6 h; metabolized to canrenoate, active with τ1/2 = 10 - 20 h.
- Delayed Effect: Takes a few days, single dose lasts 1 - 3 days.
- Highly Bound to Protein: 90-98%, can interfere with digoxin.
- Small Diuretic Effect: Only 2% of Na+ load, used to lower blood pressure via RAA system
Mechanism of MC Antagonists
- Site of Action: Distal Tubule (DT) / Collecting Duct (CD).
- Basolateral Binding to MC-Receptor: Blocks action.
- AIPs (Aldosterone-Induced Proteins): Involved in gene expression.
- NaCl Transport Dependence: Effect depends on hormonal state and high [hormone].
Rationale of use
Indications and contraindications; Adverse effects
- Indications:
- Hypertension (in combination)
- Hyperaldosteronism
- Diuretic of choice in hepatic cirrhosis
- Adverse Effects:
- Metabolic acidosis
- Interference with steroid biosynthesis (gynecomastia…)
- Contraindications:
- Hyperkalemia
- Hyponatremia
- Anuria
Discuss the complications of MI
darthvader
- DEATH
- arrhythmia
- rupture - free ventircular wall, septum or papillary muscles
- tamponade
- hart failure
- vavle disease
- anuerysm of ventricle
- dressler’s syndorme
- embolism ?(mural thrombus)
- recurrence or mitral regurg
MED
Describe the histology of cardiac muscle
Compare the muscle types
hi
Defien myocardial ischaemia, infarction and necrosis
Y2
LO
homeostatic response to pre-syncope
exam
MED
Broadly distinguish between stenosis and regurgitation
Describe atrial tachycardias
Provide a list of the tachycardias
HI
Describe the timeline of ECG changes in STEMI
own notes and Y2
The definition of a STEMI is that there is new ST elevation at the J point in two contiguous leads of >0.1 mV in all leads other than leads V2-V3
- A = normal
- B = mild ST elevation
- C = severe ST elevation
- D = Biphasic T wave with ST elevation
- E = T wave inversion
- F = returning to normal
