Cardiology Physiology Flashcards
What is atherosclerosis?
Atherosclerosis is a chronic inflammatory disease caused by deposition of lipid and a subsequent inflammatory response in the walls of arteries due to deposition of lipoproteins (plasma protein that carry cholesterol and triglycerides) which leads to occlusion and increased risk of acute CV incidents e.g. MI or CVI (stroke)
What is a key feature of atherosclerosis?
Atheroma (fibrofatty plaques) building up ≈ intimal fibrous cap + central core rich in lipids
List the risk factors for atherosclerosis. How may they be stratified?
1) Modifiable risk factors:
- Dyslipidemia: raised LDL, low HDL, raised TG
- Hypercholesterolaemia
- Hypertension/ raised BP
- Physical inactivity
- Thrombogenic factors
- Smoking
- Alcohol
- Diet
2) Non-modifiable risk factors:
- Age
- Sex
- Genetics
- Ethnicity
- Hypertension
- Diseases e.g. Diabetes Mellitus or Leiden mutation
What is the pathogenesis of atherosclerosis?
1) Initiation: i) Chronic endothelial injury/dysfunction (≈ permeability of vessel wall): - Haemodynamic disturbances (∆ flow to turbulent) - Hypercholesterolaemia - Hypertension - Smoking - Toxins - Viruses e.g. vasculitis - Immune reactions
ii) Endothelial permeability + Leukocyte adhesion
- VCAM-1, ICAM-1, P-selectin, E-selectin ≈ monocyte adhesion + migration ≈ enter tunica intima ≈macrophages
- Chemokine secretion + leukocyte recruitment
iii) Lipid accumulation - Hyperlipidemia (LDL cholesterol) ≈ lipid accumulation, endothelial impairment ≈ LDL + [O] ≈ Ox-LDL
2) Progression:
i) Macrophages phagocytose Ox-LDL:
- Macrophages engulf Ox-LDL ≈ lipid-laden foam cells
- Secrete IL-1, TNF-a, MCP-1, PDGF, FGF, TNF, IFN-a and TGFß
- Formation of fatty streak (lipid-rich core from foam cells)
ii) Smooth Muscle Proliferation - SMC proliferation + secretion of ECM proteins ≈ collagen and other ECM deposition ≈ fibrous cap ≈ stabilise plaque - Oxidative stress and chronic inflammation - Fatty streak ∆ to mature fibrofatty atheroma
3) Clinical complications - Plaque destabilisation by apoptosis/necrosis of SMCs - Reduced proliferation of ECM: imbalance between SMCs and pro-inflammatory cytokines which lead to destabilisation - Increased expression/activation of MMPs - Reduced TIMP activity/expression - Platelet aggregation + coagulation activation - Thrombus formation
What protective measure regarding cholesterol can reduce the progression of atherosclerosis?
HDL ≈ retrograde LDL transport ≈ to liver for storage, biosynthesis and ß-oxidation ≈ reduce rate of development of atheromatous plaque build up
What are/is the morphology/morphologies of atheroma?
Atheromatous (fibrofatty, fibrolipid) plaque
- Patchy + raised white/yellow 0.3-1.5cm
- Lipid core + necrotic core (tunica intima): cell debris, cholesterol crystals, foam cells + calcium (tunica intima)
- Fibrous cap (tunica intima/endothelium): SMCs, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularisation
List the arteries most susceptible to atheromatous plaque build up.
- Abdominal aorta - Coronary arteries - Popliteal arteries - Descending thoracic aorta - Internal carotid arteries - Vessels of Circle of Willis
What can cause additional variations in the morphology of a lesion?
- Calcification - Rupture/ulceration - Haemorrhage - Thrombosis - Aneurysmal dilatation
What is a major complication of atheromatous plaque build up in the abdominal aorta?
Abdominal aortic aneurysm ≈ medical emergency ≈ rupture into retroperitoneal cavity ≈ pain, hypotension + pulsatile mass
What are the haemodynamic forces allowing an aneurysm to occur?
LaPlace’s Law states that Tension = Pressure x Radius thus wall must be strong enough to withstand tension generated by the pressure (in all directions) multiplied by the radius of the vessel.
Aneurysm: Pressure either side of aneurysm equilibrates and so does P in weakening wall ≈ greater tension as P is the same ≈ weakening wall (radius increases and P remains the same) ≈ consistently swell with radius increasing to compensate
List the types of aneurysms.
1) Saccular: localised dilatation of vessel wall bulging unilaterally ≈ small area forming sac-like swelling
2) Fusiform: local dilatation of vessel bulging bilaterally
3) Dissection: layer of endothelium separates (shear stress) ≈ false lumen ≈ blood flow between layers ≈separate further
4) Pseudoaneurysm: breach in vessel wall ≈ pseudoaneurysm neck ≈ pseudoaneurysm sac-like bulge
What are the clinical features of atherosclerosis? What do clinical features depend on?
1) Aneurysm + rupture: mural thrombosis; embolisation; wall weakening
2) Occlusion by thrombus: plaque rupture; plaque erosion; plaque haemorrhage; mural thrombosis; embolisation
3) Progressive plaque growth: critical stenosis
What is the prevention of complications and clinical features of atherosclerosis and how may these be stratified?
1) Primary prevention (prevent disease, risk profile):
- Smoking cessation
- Control of hypertension
- Weight reduction
- LDL lowering
- Reduce caloric intake
2) Secondary prevention (prevent complication, have disease):
- Anti-platelet drugs in thrombosis
- Lower blood lipid levels
Why not just use medication for treatment of disease?
- Healthy lifestyle reduces requirement for medical treatment
- Lack of adherence
- Can be treated without medication
- Pleiotropic benefits e.g. cancer risk reduction
List the effects of lifestyle factors on CVD risk.
- Reduce dietary fat
- Reduce blood cholesterol
- Exercise - Mindfulness
- Hydration
- Balanced diet + portions
What food groups make up the Eat-well guide? List the nutrients.
- Fruit + Vegetables: fibre and antioxidants
- Starch (carbohydrates): wholemeal ≈ soluble + insoluble fibre + carbohydrates - Dairy and alternatives:
- Protein: essential AAs + vitamin B12 + omega 3 FAs
- Dairy: calcium + protein
- Fat: Polyunsaturated fats + unsaturated fats
List the key lifestyle recommendations for primary and secondary prevention of CVD.
1) Dietary fats: Replace SFA (meat, meat products, cheese, biscuits and cakes) with MUFA (olive oil, peanuts, almonds, seeds and avocado) + PUFA (omega-3, linseed, rapeseed, walnuts, seed oils, nuts and spreads)
2) 2 portions of fish
Primary prevention: Eat 2 portions of fish + 1 portion of oily fish (140g)
3) Nuts, seeds and legumes 4-5 portions per week
4) Minimise trans fatty acids ≈ < 2% food energy
5) Wholegrain varieties of starchy foods
6) Reduce salt intake to < 6g/day
7) 5 portions of fruit and vegetables
8) Alcohol intake ≈ 14 units per week on a regular basis
9) Maintain a healthy weight
10) Increase physical activity
What patients should get cholesterol-lowering treatment? Outline the goal of treatment.
- Previous CV event e.g. MI, angina, CABG, angioplasty, CVI or TIA, PVD
- DM + 40 years old <
- CKD Stage 3-5
- Schizophrenia and/or bipolar disorder + 40 years old < - Rheumatoid Arthritis
- Genetic lipid disorders - Asymptomatic people with a > 10% of developing CVD within 10 years (estimated using CV risk assessment tool - ASSIGN CV risk assessment calculator)
Goal: Reduce non-HDL cholesterol
List the factors used to outline risk of developing CVD in 10 years time. What is this called?
- Age
- Sex
- Smoking
- Systolic blood pressure
- Lipid profile
- Family history of premature CV disease
- Diabetes mellitus
- Rheumatoid arthritis
- Social deprivation
ASSIGN tool
List the 6 main classes of cholesterol-lowering drugs. List a drug from each class.
- Statins (Simvastatin; Pravastatin; Atorvastatin; Rosuvastatin)
- Fibrates (Fenofibrate)
- Ezetimibe (Ezetimibe)
- Bile acid sequestrants (Colestyarmine)
- Nicotinic Acid (Nicotinic Acid)
- PCSK9 inhibitors (Inclisiran; Alirocumab)
List the MOA for statins.
Hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase) inhibitors ≈ reduced HMG-CoA to mevalonic acid (MVA) ≈ reduced conversion to cholesterol ≈ reduced cholesterol synthesis ≈ increase ability to remove via liver
List the side effects of statins.
- GI disturbances - Rash - Insomnia - Myositis (inflammation in muscles) - Angio-oedema
List some key prescribing points for statins.
- Contra-indicated in acute liver disease + pregnancy
- Acting length (SPAR): Simvastatin + pravastatin < atorvastatin + rosuvastatin thus taken at night to reduce peak cholesterol synthesis in early morning
- Atorvastatin beneficial in patients with homozygous familial hypercholesterolaemia
- After starting statins, check lipid levels + LFTs 4-8 weeks and if any dose change. If stable, reduce frequency to annually ≈ LFTs to check for hepatotoxicity (small risk)
- Atorvastatin and simvastatin both prodrugs metabolised by cytochrome P450 system so some drug interactions possible and contraindicated by if liver failure
What is the MOA of fibrates?
- Activate lipoprotein lipase (LPL) ≈∆ plasma lipoproteins
- Reduce plasma TGs and Cl - Reduce increased VLDL
- Clearance of LDL by liver
- Increased HDL and reverse cholesterol transport
When would you give fibrates?
Second line
- Statins not tolerated (after 3 tries of statin + dose reduction)
- Combined with other lipid
- Lowering drugs in severe treatment resistant dyslipidemia
- Considered in mixed dyslipidemia (raised TG + low HDL)
- Low HDL and high risk of atheromatous disease (T2DM)
List some side effects of fibrates.
- Myositis (especially if renal impairment)
- GI disturbances
What are some key prescribing points for fibrates?
- Avoid in ALD ≈ increased risk of myositis
- Contraindicated in hepatic and renal insufficiency
What is the MOA of ezetimibe?
Inhibit transport protein for cholesterol in brush border of enterocytes (NPC1L1) in duodenum ≈ reduce intestinal cholesterol absorption
What are the side effects of Ezetimibe?
- GI symptoms - Nausea - Abdominal bloating - Constipation - Diarrhoea
What are some key Rx points for Ezetimibe?
- Contraindicated in pregnancy and lactation
What is the MOA of bile acid sequestrants?
Binds bile acid ≈inhibit cholesterol absorption
- Sequesters bile acids in intestine ≈ X enterohepatic recirculation ≈ increase metabolism of endogenous cholesterol into bile acids
When would you use Colestyramine cf Statins?
Third line, statins or ezetimibe or fibrates not tolerated.
- FH
What are some key side effects of Colestyramine?
- Nausea
- Abdominal bloating
- Constipation - Diarrhoea
What are some key Rx points about Colestyramine?
- Taste + texture of colestyramine ≈ reduced adherence
- Interferes with absorption of other drugs (lipid-soluble) + vitamins (DEAK) - Contraindication in complete biliary obstruction
What is the MOA for Nicotinic Acid?
Diacylglycerol acyltransferase-2 (DGAT2) inhibitor ≈ Inhibit production of VLDL; lower LDL; lower TG; increase HDL-cholesterol ≈ control of dyslipidemia
What line of therapy is Nicotinic Acid?
Combination or 4th line
- In combination with statins
- Statins not tolerated + other lipid-lowering medicines not tolerated (fibronates, bile acid sequestrates, ezetimibe)
- HDL raising agent
List some side effects of Nicotinic Acid.
- Flushing - Itching - Nausea - Numbness and tingling - Worsening of gout - Diabetes - Angina
What are some key Rx points for Nicotinic acid?
- Regular blood tests ≈ LFTs (potential hepatotoxicity)
- Increase GI bleeding + infection rates
- Contraindication in peptic ulcer disease + arterial bleeding
What is the MOA for PCSK9i (Alirocumab; Inclisiran)
PCSK9i ≈ X cleavage of LDLr ≈ X LDLr shedding ≈ LDL uptake and metabolism
What line of therapy are PCSK9 inhibitors?
5th line or Severity
- All therapies not tolerated (statins, ezetimibe, fibrates, bile acid sequestrates, nicotinic cid)
- Familial hypercholesterolaemia
List some side effects of PCSK9is?
- Nausea
- Back and joint pain - Soreness or itchiness
What is the main Rx point for PCSK9i?
- Specialist only
What are the possible effect(s) for concurrent administration of the statin atorvastatin with: Ciclosporin? Clarithromycin? Grapefruit juice?
1) Ciclosporin (systemic) ≈ severe + monitor Explanation: Ciclosporin ≈ markedly increases exposure to atorvastatin ≈ myopathy (rhabdomyolysis) + renal failure. Atorvastatin ≈ increase exposure to ciclosporin slightly.
Action: - Close monitoring - Avoid concurrent use - Safety net with myopathy symptoms to report if experienced by pt - Reduce dose to 10mg daily
2) Clarithromycin (systemic) ≈ severe + monitor
Explanation: Clarithromycin ≈ moderately increases atorvastatin exposure ≈ rhabdomyolysis risk. Previous rhabdomyolysis reported in patient taking
Action:
- Temporarily remove statin or reduce dose dose (< 20mg PO).
- Reduce dose ≈ <20mg daily
- Safety net with myopathy symptoms to report if experiences by pt
3) Grapefruit juice (systemic) ≈ mild + adjust
Explanation: Large volumes of grapefruit juice (≈ furanocoumarins) ≈ increase atorvastatin exposure ≈ smaller amounts + separate administration by 12 hours to reduce effects
Action:
- Avoid large volumes of grapefruit juice (1.2L)
- Safety net: Advise patients to report rhabdomyolysis symptoms
- Muscle pain, tenderness or weakness
If a patient is not achieving targets for cholesterol despite evidence-based prescribing, what should be checked?
- Check adherence
- Exclude + manage common secondary causes of dyslipidemia: excess alcohol, uncontrolled diabetes, hypothyroidism, liver disease, nephrotic syndrome
- Consider Ddx - Specialist referral
What is the criteria for an ASSIGN score to ensure high risk?
> 20 ASSIGN SCORE
What are the functions of the CVS?
- Bulk flow of materials: gases, nutrients, hormones and waste
- Temperature regulation
- Homeostasis
- Host defence
- Reproduction
What are the major components of the CVS?
- Heart: pump≈ blood flow in closed system
- Arterial system: conductance system of oxygenated blood away from heart
- Microcirculation: nutrient transfer, waste and water occurs
- Venous system: capacity vessels storing and returning deoxygenated blood to the heart
Is the circulatory system parallel or series and why?
CVS is parallel, not series, as blood must be able to bypass organs ≈ less metabolic demand ≈ require less perfusion and venous return occurs in opposite flow
What does the parallel arrangement of vessels allow?
Independent regulation of blood flow to different organs which can adapt to metabolic demands of the tissues
- Independent regulation of blood flow
- Adapts to metabolic demands of tissues
What occurs if there is a lack of perfusion?
Hypoxia ≈ ischaemia ≈ necrosis
Which organs receive blood flow and what are the proportions of blood flow received?
- Brain ≈ 13%
- Heart ≈ 4%
- Skeletal muscle ≈ 20% - Skin ≈ 9%
- Kidneys ≈ 20%
- Abdominal organs ≈ 24%
- Other ≈ 10%
How do the properties of blood vessels alter the function? Use an example of a vessel.
Structure ≈ function Consider: - Elasticity - Smooth muscle - Fibrous tissue - Wall thickness - Diameter (lumen)
- Aorta: highly elastic + little smooth muscle with more fibrous tissue; large diameter ≈ elastic + reduced vasoconstriction ≈ smooth blood flow + high blood flow
- Artery: elastic tissue + smooth muscle; thick wall + lumen ≈ elasticity to smooth pulsatile flow + vasoconstriction to change lumen diameter; + blood flow
- Arteriole: elastic tissue + smooth muscle ≈ ∆ lumen diameter via vasoconstriction + smooth pulsatile flow to reduce pressure at capillaries
- Vein ≈ little elastic tissue with little smooth muscle + large lumen ≈ little vasoconstriction + transport blood under low pressure
- Venule: No elastic tissue + no smooth muscle; thin wall ≈ transport blood under low pressure from capillaries via venous system into larger, true veins
- Capillary: thin (one-cell thick) + no elastic tissue ≈ diffusion of substances
What is the homeostatic control of blood pressure?
BP reference set-point —> MAP —> baroreceptors —> feedback signal —> brain medulla vasomotor centres (reference set point) —> SNS (via sympathetic cardiac nerve impulses if low BP) / PSNS (via vagus nerve if high BP) —> effectors ≈ BV + heart (or kidneys) —> ∆ MAP
What are the acute responses to elevations in BP?
Situation: High BP —> Increased carotid sinus nerve impulses and vagus nerve impulses —> Medulla oblongata —> Reduced sympathetic cardiac nerve impulses and increased parasympathetic = HR, inotropy and vasoconstriction reduced
What are the blood pressures like across the systemic circulation? Why?
Changes from pulsatile due to elastic recoil of blood vessels such as aorta and muscular arteries compared to smoothened out flow rate by variable muscular walls in tunica media which alter their vasomotor tone to increase laminar flow rate for adequate perfusion at capillary beds which have high resistance due to being one cell thick
What is the arterial pulse pressure wave? What can it be used to calculate (x2)?
Time continuous variable graph showing changes in blood pressure and the pulse pressure indicated by the difference between systolic and diastolic pressure;
Pulse pressure = SBP - DBP
MAP = 1/3 (SBP-DBP) + DBP
What is MABP? How is it calculated?
average pressure in patient arteries during one cardiac cycle
MABP = DBP + 1/3 PP (SBP - DBP)
What are the postural effects of standing?
Standing ≈ increase P by 1mmHg for 1.36cm below surface ≈ 90mmHg by feet
- Increase P as you go down ≈ 1.36cm = 1mHg
- 100mmHg @ heart level
- Leg oedema ≈ 10-20% of blood volume within 15-30 minutes
Why does the postural effects of standing not result in permanent oedema?
Physiologically functioning measures ≈ venous valves + venous pump ≈ venous return
What may a sudden change from supine to standing result in and why? How is this corrected?
Supine to standing ≈ 500ml blood from upper body to legs ≈ reduce venous return ≈ reduced CO ≈ reduced BP ≈ reflex vasoconstriction in legs to facilitate venous return and end-diastolic volume is lagging..few s to function
Decreased BP —> decreased baroreceptor activity —> integration of afferent info into brainstem —> increased sympathetic and decreased parasympathetic tone —> increased peripheral vascular resistance, heart rate, vasoconstriction and increased CO to restore BP
What is vascular compliance?
relationship between volume of blood and pressure generated by presence of the volume and property of vessel undergoing deformation
What is a non-compliant and compliant vessel and give examples?
1) Non-compliant: rigid tubes resist expansion when internal pressure rises. Big change in P due to small change in V
E.g. Capillaries + arterioles (smaller so easier to become non-compliant)
2) Compliant: Elastic walls ≈ swell when internal pressure rises. Big change in V with little changes in P
E.g. arteries, veins
How does compliance change with: age; vasoconstriction?
Compliance decreases in both age and vasoconstriction as more rigid ≈ little change in volume causes a larger change in pressure
What is Laplace’s Law?
Physical law stating tension within wall of a vessel with partial pressure depends on the radius of the sphere (thickness)
T = PR
What are the practical consequences of LaPlace’s Law?
1) Control of blood flow:
- Low tension required to oppose blood pressure in arterioles
- Smooth muscle control of arteriole and precapillary sphincters are sites of tissue blood flow regulation
2) Capillaries
- Extremely thin and still withstand pressure ≈ T = PR so radius is low + pressure is reduced thus less tension generated ≈ less muscular wall required to overcome tension produced
- Thin walls required for exchange process
3) Aneurysm
- Pressure either side of bulge equilibrates and so does pressure in weakening of wall ≈ greater tension as pressure is the same; weakening wall (radius increases and P is the same) ≈ consistently swell and eventually burst
What factors affect flow of a fluid through a vessel?
- Radius (directly proportional) - Pressure gradient (directly proportional) - Length of the vessel (indirectly proportional) - Thickness of the fluid (indirectly proportional) - Viscosity
What does a reduction in diameter cause?
∆D (∆r) —> reduce flow rate as increase resistance —> as Poiseulle’s Law shows R = (π)r4/8nl —> therefore small reduction of radius/diameter ≈ large change in resistance as radius is to the power of 4—> increase R
How does viscosity change/stay same and where?
viscosity of plasma and water remains constant but whole blood changes according to haematocrit
- More Hct ≈ more viscosity
What is the relationship between viscosity and fluid flow velocity?
Reduced viscosity ≈ increased blood flow velocity as blood is a thixotropic fluid (energy put in to make it move) ≈ less energy required to make it move
What is the relationship between arterial pressure, cardiac output and total peripheral resistance?
AP = CO x TPR
What are the 3 categories of regulation of arteriolar radius and what aspects under each?
1) Neural
Vasoconstrictor: sympathetic nerves
Vasodilator: NO-releasing nerves
2) Hormonal:
Vasoconstrictor: adrenaline, angiotensin II, vasopressin
Vasodilator: adrenaline, atrial-natriuretic peptide
3) Local:
Vasoconstrictor: myogenic response, endothelin-1
Vasodilator: reduced oxygen, K+, CO2, H+, adenosine, nitric oxide, bradykinin
What are the types of fluid flow?
1) Laminar fluid flow
- Fluid molecules travel in layers
- Middle layer encounters least resistance cf outer layers ≈ shear force
2) Turbulent flow:
- Disrupts flow ≈ increased resistance
What is Reynold’s number?
Used to indicate whether flow is likely to be laminar or turbulent
- given system there is critical value for Re above which turbulence is highly likely
Re = (velocity) x (radius of vessel) / viscosity
List 2 factors which increases Re.
- high velocity flow
- large diameter vessels
- low blood viscosity
- abnormal vessel wall
What allows the heart to act in a functionally integrated manner and what is this collective unit known as?
Cardiomyocytes contain intercalated discs @ Z-line ≈ connected via GAP junctions (connexin hexamer ≈ connexon) ≈ flow of AP and ions simultaneously ≈ influx of Calcium via CaVg channels ≈syncytium ≈ simultaneous, synchronised depolarisation ≈ synchronised contraction of cardiac tissue
What controls the contractions?
Pacemaker cells ≈ self-excitable (autorythmic) ≈ SAN in RA (by sulcus terminalis, between SVC and coronary sinus) ≈ myogenic ≈ determines HR ≈ chronotropy
What are the three types of cardiac action potentials and what are the distinguished by?
1) Pacemaker potentials
- Spontaneous depolarisation
- Slow depolarisation
- Driven by calcium slowly
2) Non-pacemaker potentials
- Rapid depolarisation
- Driven by sodium rapidly and prolonged by calcium
3) His-Purkinje potentials
- Rapid depolarisation
- Spontaneous depolarisation
- Driven by sodium rapidly and prolonged by calcium
What is the membrane potential changes in nodal tissue?
Phase 1: @ - 60mV ≈ Funny currents (If) ≈ pacemaker potential + T-type Calcium channels ≈ threshold + depolarisation
- Funny currents (If): -60mV ≈ F-type Na+ channels open at more negative membrane potentials (-60mV) ≈ gNa+ in (‘funny currents’) and K+ channels close ≈ gK+ reduced ≈ pacemaker potential
- T-type Ca2+ channels open @ -50mV ≈ gCa++ increases ≈ Ca2+ in ≈ depolarisation
Phase 2: @ -40mV Slower, sustained depolarisation via L-type Ca2+ channels ≈ gCa++ increases ≈ Ca++ in - Calcium influx via L-type calcium channels ≈ depolarisation
Phase 3: Repolarisation - @ +20mV KVg channels open ≈ increased gK+ ≈ increased conductance ≈repolarisation as potassium efflux occurs - CaVg L-type close ≈ reduce gCa++ ≈ reduced depolarisation + repolarisation
What is the membrane potential changes in atrial and ventricular cardiac tissue?
Phase 0:
- Rapid depolarisation due to NaVg opening at -75mV ≈ gNa+ ≈ Na+ in
Phase 1:
- NaVg close ≈ reduced gNa+
Phase 2:
- L-type CaVg open @ 10mV ≈ gCa++ ≈ Ca++ in ≈ plateau
Phase 3:
- Rapid repolarisation: gCa++ ≈ increased IC Ca++ ≈ K+ channels open ≈ gK+ efflux
- L-type CaVg close ≈ reduced gCa++
Phase 4:
- Stable resting membrane potential where gK+ > gNa+ (50:1)
What is the effect of hypoxia on heart rate and why?
Cellular hypoxia ≈ depolarises the cell ≈ ∆ phase 3 hyper-polarisation ≈ reduced pacemaker rate ≈ bradycardia
What is the autonomic nervous system innervation of the heart? What effects do the respective functional divisions of the ANS have on pacemaker activity?
1) PSNS: Vagus nerve (CN X) —> SAN + AVN
- ACh @ M2R ≈ Gai ≈ reduce cAMP ≈ reduce rate of phase 0 depolarisation + hyperpolarise membrane potential (= increase extent + duration of opening of K+ channels ≈ increase gK+)
2) SNS: Sympathetic chain ≈ sympathetic nerves —> atria + ventricles
- NA @ ß1R ≈ Gas ≈ increase cAMP ≈ increase rate of phase 0 depolarisation ≈ increase gCa++ + increase gNa+ via funny channels
What is the electrical conduction pathway in the heart?
Coordinated electrical activity: pacemaker activity of SAN (RA) ≈ initiate process ≈ depolarisation spreads due to functional syncytium (electrically connected via GAP junctions) ≈ SAN in RA —> internodal pathway + interatrial pathway —> AVN (critical delay ≈atrioventricular flow) —> L + R Bundle of His (interatrial septa) —> Purkinje fibres
What are the rates of depolarisation in the heart? Which is the most important one and why - what is it termed?
SAN (90) > AVN (60) > BoH (50) > PF (40) > V (30)
SAN = ‘pacemaker’
What are the rates of conduction throughout the heart? In what unit of measurement is this? Any delays?
Conduction measured in m/s as it is a speed of distance/time (m/s)
- SAN to AVN ≈1m/s (internodal pathways) ≈ 0.03s
- Internodal pathways ≈ 1m/s
- Atrial + Ventricle fibres ≈ 0.3-0.5m/s
- AVN delay ≈ 0.09s
- Penetrating portion delay ≈ 0.04s
- AVN + BoH ≈ 0.01m/s
- PF ≈ 1.5-4m/s
What is Einthoven’s Triangle?
Equilateral triangle with heart at centre formed by three bipolar limb leads
- Lead I: positive electrode on left arm + negative electrode on right arm ≈ potential difference between two arms
- Lead II: positive electrode on left leg and negative electrode on right arm
- Lead III: positive electrode on left leg and negative electrode on left arm
- Reference electrode: Electrode on right leg ≈ reference electrode for recording purposes
How are the degrees formed of the heart and what is this called?
Einthoven’s triangle (equilateral) ≈ broken apart + collapsed + superimposed over heart ≈ axial reference system
- Positive electrode for lead I (Left arm) ≈ 0º relative to heart (along horizontal axis between LA and RA)
- Positive electrode for lead II (RA-LL) axis: +60º cf to heart
- Positive electrode for lead III (LA-LL): +120º cf to heart
What determines the magnitude of electrical signals?
1) Current (proportional to tissue mass)
2) Direction of signal
What equation can be used to calculate observed signal?
E x CosƟ (= observed signal)
E = electrical event
Ɵ = angle between event + ECG lead
What change to angle would yield a greater observed signal?
Smallest angle ≈ greater observed signal
Why is there an isoelectric period after the P wave?
P wave ≈ impulse travelling within AVN (conduction velocity retarded) + in BoH
What may be occurring if the QRS complex is longer than 0.12-0.20s?
Prolonged duration of QRS complex ≈ > 0.12-0.20s ≈ impairment of conduction within ventricles ≈ e.g. bundle branch blocks or abnormal pacemaker site (ventricular foci)
Why is there an isoelectric period between the S and T waves?
ST segment ≈ isoelectric period between S and T waves ≈ time when both ventricles completely depolarised ≈ plateau phase of ventricular action potentials
Why is the ST segment of particular relevance?
DDx of ventricular ischaemia or hypoxia e.g. myocardial infarction as ST segment elevated (STEMI) or depressed (NSTEMI)
Why is the T wave a positive deflection?
Last cells to depolarise are the first to repolarise (subepicardial region cf subendocardial region) ≈ repolarisation waves orientated opposite to depolarisation waves ≈ repolarisation moving away from positive recording electrode ≈ positive voltage
Is the T wave longer in duration cf QRS complex and why?
T wave (0.12s) > QRS complex (0.12-20s)≈repolarisation wave does not use high-velocity bundle-branch of BoH or PFs cf cell-cell conduction ≈ conduction of repolarisation slower than depolarisation
What can prolonged QT interval indicate?
Prolonged QT interval ≈ some types of tachyarrythmias - Must distinguish if QT interval is excessively long
What is angina pectoris? What is the characteristic distribution of pain?
Ischaemia ≈ inadequate supply of oxygen to heart ≈ chest pain (angina)
- ‘Severe crushing’
- Retrosternal pressure;
- Radiation: Chest, arms, neck + jaw
What exacerbates/triggers angina pain and outline the pathophysiology of pain?
Triggers/exacerbations: - Exertion - Cold - Excitement - GTN/Rest
Chemical factors (K+, H+ and adenosine) ≈ local vasodilation factors + sensitising soup ≈ increase blood flow + pain
What does the P wave represent? Timings? Features?
- P Wave: Atrial depolarisation = < 0.12s + < 0.25mV
• Positive in leads I and II
• Inverted in aVR
• Isoelectric after P wave as impulse travels within fibrous septa with velocity retarded
What does the Q wave represent? Timings? Features?
- QRS Complex: Ventricular Depolarisation = 0.08-0.12s
• Q wave is septal depolarisation from L –> R
• R wave is ventricular depolarisation
• S wave is ventricular depolarisation
What does the T wave represent? Timings? Features?
- T Wave: Ventricular repolarization
• Can have early take off T wave in young person
• Inverted in VR and V1 and V2 in young
What does the PR interval represent? Timings?
PR Interval: Atrial Depolarisation = 0.12-0.20s
• Lengthened in AVN Delay
What does the QRS complex represent? Timing?
QRS Complex: Ventricular Depolarisation = 0.08-0.12s
What does the QT interval represent?
QT Interval: Ventricular depolarisation + Repolarisation
What is the overview of treatment/how may angina treatment be divided into two categories?
Treatment to reduce chest pain symptoms + treatment to prolong survival
1) Reduce chest pain symptoms: - ß-blockers - Nitrates - Calcium channel antagonists - Nirocandil - Ivabradine - Ranolazine
2) Prolong survival:
- ß-blockers
- Aspirin
- Statins
- ACEi
- ARBs
When is the heart e.g. LV best perfused? Show this on a graph.
Heart perfused (coronary blood flow to myocardium) best during diastole. In systole P rises in ventricle ≈ P of LV > P of aorta ≈ semilunar valve opens ≈ blood out ≈ P in aorta rises in systole then P in aorta and LV reduces ≈ P of LV > aorta ≈ aortic valve shuts ≈ diastole ≈ LV pressure reduces in diastole but aorta P reduces slowly + aortic valve shut ≈ retrograde flow ≈ blood flows via Ostia in aortic sinus into RCA and LCA ≈ cycle repeats
What is the ‘coronary window’ and what is the pressure difference in this time?
Period of time for coronary flow during diastole whereby aortic P > ventricular P ≈ blood flow via coronary sinus into RCA + LCA
What potentially physiological/pathophysiological changes to coronary window can occur and what does this result in?
1) Increased HR (= narrow coronary window): increased rate≈ tachycardia ≈ reduced diastolic filling time due to increased systole ≈ narrow coronary window
2) Aortic stenosis/ increased residual volume (increased EDV, reducing pressure difference): increased volume ≈ increased pressure in left ventricle ≈ reduced pressure difference between aortic P and ventricular P ≈ reduced coronary window
3) Mitral valve stenosis or Aortic regurgitation (reduced diastolic volume): Reduced diastolic arterial P thus pressure difference reduced OR retrograde blood flow from aorta and reduced P in diastole ≈ reduced coronary window
What is the auto regulation of arteriolar radius? How is this controlled?
Tissue demand ≈ increase arteriolar radius ≈ blood flow
- Metabolic control: Myocyte produces local vasodilator byproducts (e.g. adenosine) ≈ vascular SMCs relax (potentially via intermediate produced by endothelial cells)
What are the main types of ischaemia?
- Coronary ischaemia: Atherosclerosis ≈ coronary ischaemia ≈ angina (stable angina); ≈infarction (≈ unstable angina) ≈ MI
- Sudden ischaemia: Thrombosis ≈ stenosis/occlusion ≈ ischaemia (≈ unstable angina) ≈ myocardial infarction
- Coronary spasms: Oscillatory narrowing of arteries ≈ variant ischaemia ≈ variant angina due to hypoxia
What molecular pathophysiological mechanism results from ischaemia and what can it cause?
Ischaemia ≈ cellular calcium overload ≈ cell death + dysrhythmias
How does atherosclerosis cause ischaemia regarding impact on flow?
Atherosclerotic plaque build up≈ atherosclerotic changes ≈ reduce diameter/radius of artery (stenosis) ≈ length and viscosity remain same (denominator) however radius reduced significantly ≈ radius to power of 4 = significantly amplified ≈ significant reduction in flow rate ≈ reduced blood flow ≈ hypoperfusion ≈ ischaemia ≈ infarction (calcium toxicity ≈ cardiomyocyte death)
What are the classes of angina? Give a potential common cause of each form of angina and what type of ischaemia causes each type of angina.
1) Printzmetal’s Variant Angina: Vasospasm≈ coronary spasm supply ischaemia
- Coronary artery spasm
- Uncommon
- Incomplete understanding; sometimes associated with atherosclerosis
2) Unstable angina: Thrombus ≈ supply ischaemia
- Thrombus around ruptured atheromatous plague (unstable atheromatous plaque) w/o complete occlusion of vessel (similar to MI)
- Occurs at rest/ low exertion; less exertion required cf stable angina
3) Stable angina: Fixed stenosis ≈ demand ischaemia
- Fixed stenosis of coronary arteries
- Predictable chest pain on exertion
- Treat: Reduce workload of heart ≈ reduce oxygen requirement
- Use drugs to prolong survival: aspirin, statins and ACEi
What is the classic triad of angina symptoms?
- Chest pain: retrosternal, heaviness, pressure, weight, burning, tightness
- Radiation: shoulder-tip pain, neck, jaw, inner arms, epigastrium, band-like discomfort
- Relieved: remove exertion + GTN (glyceryl trinitrate) spray + after 10 minutes
Do all symptoms have to be present and which groups may have this?
Atypical angina (2/3) or silent myocardial ischaemia + angina (1/3) - absent of chest pain
Silent myocardial ischaemia: - Women - Elderly - Transplanted hearts - Diabetes (autonomic neuropathy)
How do anti-anginal drugs work primarily?
Anti-anginal drugs ≈ reduce metabolic demand of heart ≈ reduced oxygen requirement ≈ reduced % of ischaemia precipitating angina
- Pre-load≈ ∆ volume filling heart: ventricles are compliant so large change in volume ≈ small change in P
- After-load: ∆ volume leaving heart e.g. vasodilation ≈ reduce aortic after load pressures
- Metabolic demand: reduce sympathetic drive + increase PSNS tone; reduce contraction rate (chronotropy)
How do different anti-anginal drugs work broadly?
1) Vasodilators: organic nitrates; nirocandil, calcium antagonists - Reduce preload or after load
2) Slow heart rate: ß-blockers + ivabradine
and r
- Reduce metabolic demand of the muscle
What is pre-load? What contributes to preload broadly?
Initial stretching of cardiomyocytes prior to contraction ≈ muscle sarcomere length
- HR
- Atrial contractility
- Ventricular compliance
- Venous return
- Aortic pressure
What is after-load (≈ σ)? What contributes to after-load?
Load heart must eject blood against ≈ closely related to aortic pressure
σ = ventricular wall stress P = Pressure r = radius h = wall thickness
Factors:
- Aortic pressure
- TPR
Does functional hypertrophy increase or decrease ventricular wall stress and why?
Functional hypertrophy (e.g. LV) ≈ increased sarcomere units per area ≈ thickened wall ≈ increase h; P x r remains same ≈ reduced ventricular wall stress ≈ reduced after load as sarcomere units share tension (P x r)
What effect does an increased after-load have on stroke volume and why?
Increase after load ≈ Frank-Starling curve down ≈ reduce SV h/e increased left-ventricular end-diastolic pressure (LVEDP).
- Increase in after-load ≈ decreased velocity in fibre shortening (force-velocity relationship) ≈ reduced rate of volume ejection ≈ more blood left within ventral ≈ end-systolic volume increased (increased pressure)
Why does decreasing arterial pressure, increase stroke volume?
Decrease arterial pressure ≈ decreased after-load ≈ ventricle requires less P to open aortic valve (reduced pressure gradient aorta:LV) ≈ valve open ejection velocity increased (b/c decreased after load ≈ increased velocity of cardiac fibre shortening) ≈ increased ejection volume ≈ reduced ESV ≈ less blood in LV added to by ventricular systole ≈ reduced EDV ≈ decrease in EDV < decrease in ESV thus SV increased (SV = EDV - ESV)
What effect does increased after load have on pre-load and is this direct?
Afterload increase ≈ reduced SV ≈ increase LVEDP ≈ end-systolic volume increased (incomplete ejection due to decreased velocity in fibre shortening) ≈ residual volume ≈ residual volume added to end-diastolic volume ≈ secondarily increases pre-load via Frank-Starling Law
If SAN is 90-100bpm, why is actual heart rate approximately 72bpm?
Parasympathetic input ≈ vagus nerve (CNX) ≈ ACh at muscarinic receptors (M2) target cells ≈ decrease slope of pacemaker potential ≈ negative chronotropic effect ≈ decrease HR
How is heart rate increased from 72bpm?
Reduced parasympathetic tone + Increased sympathetic tone via sympathetic trunk ≈ Reduced inhibition via ACh at M2r + NA @ ß1 adrenoceptors ≈ increase slope of pacemaker potential ≈positive chronotropic effect + positive inotropic effect ≈ increase HR and force of contraction
List classes of anti-anginal drugs.
1) ß-blockers
(Bisoprolol, Atenolol)
2) Calcium antagonists
(Amlodipine; Lercanidipine; Diltiazem; Verapamil)
3) Organic nitrates (GTN, isosorbide mononitrate)
4) Potassium channel activators (Nicorandil)
5) Other (Ivabradine; Ranolazine)
What is the MOA of ß-blockers?
ß1 antagonist in heart + kidneys –> reduce Gas –> reduce cAMP –> reduce PK –> reduce chronotropy and inotropy and antidysrhythmic action
What are the side effects of ß-blockers?
- Bradycardia
- Confusion
- Dizziness
- Dry eye
- Dyspnoea
- Erectile Dysfunction
- Fatigue
- Nausea
- Peripheral coldness
- Visual impairment
- Syncope
What is the MOA of CCBs?
X opening of L-type CaVg ≈ block Ca2+ entry ≈ inhibit calcium entry upon depolarisation ≈ reduce chronotropy + inotropy –> reduce after-load + dilate coronary vessels
List the side effects of CCBs.
Headache (cerebral flow)
Constipation (reduced GI flow)
Flushing/heat
Ankle oedema (increased diameter causes reduced P –> FS Fluid Exchange)
What is the MOA of Nitrates?
Metabolised to NO ≈ relax SMCs ≈ vasodilation ≈ increased flow to meet demand ≈ reduce preload and EDV (less F-S mechanism) + dilation of collateral coronary vessels (higher [NO]) to reduce afterload
What is the MOA of Potassium channel activators?
K+-ATPase activation (efflux) ≈ hyperpolarization ≈ reduced contraction of smooth muscle ≈ reduced afterload (increase EF) + reduced venous return (EDV)
What are the side effects of Nicorandil.
Headaches
Dizziness
Flushing
What is the MOA of Ivabradine?
Inhibit F-type channels ≈ reduce If ≈ Reduce Na+ ≈ reduce pacemaker activity
What is the MOA of Ranolazine?
Inhibit Na+ channel ≈ indirectly stop Ca2+ in cardiac
What is acute coronary syndrome?
Umbrella term for syndrome, collection of symptoms, due to decreased blood flow in coronary arteries (ischaemia) ≈ unstable angina of coronary artery disease/STEMI/NSTEMI
List the three subtypes of ACS?
1) Unstable angina:
- Variable ECG changes
- Normal CTn
2) Non-ST elevation myocardial infarction (NSTEMI):
- Variable ECG changes
- Elevated CTn
3) ST elevation myocardial infarction (STEMI):
- ECG meeting STEMI criteria
- Elevated CTn
What are the risk factors for cardiac disease?
1) Modifiable - Smoking (pack years) - BP: diagnosed when? Treated or untreated? - Cholesterol - Diabetes - Weight/diet/lifestyle
2) Non-modifiable
- FH (M < 55 ; F < 60)
- Sex
- Ethnicity
How would you take a history for a patient presenting with chest pain.
- PCx: Pain; Dyspnoea; Palpitation; Syncope; Ankle oedema; Calf pain; Syncope
- HPCx: SOCRATES + other Sx
- PMHx: Illness + investigations ≈ CVD; HTN; DM; HCL; Rheumatic fever; Murmur; CT disease
- DHx: OTC, P, Illicit, Allergies ≈ OTC; NSAIDs; Herbal; Illicit
- FHx: Premature death (F = 60; M = 55); Sudden unexplained death; FH; Thrombophilia
- SHx: Smoking, Alcohol, Illicit drugs occupation, stress, domestic situation
- SEx: Cardiology; Respiratory; GI; Renal; Liver; MSK; Neurology; Dermatology
- ICE
How can you gain more information in a history from a patient presenting with chest pain?
SOCRATES
- Site: Chest/ Epigastrium/ R or L hypochondrium/R or L lumbar/ Umbilical/ R or L iliac region/ Hypogastrium
- Onset: Day/Gradual/Sudden/Precipitants/Similar Sx
- Character: Sharp/Stabbing/Heavy/Crushing/Ache
- Radiation: Arms/Back/Neck/Jaw/Abdomen
- Associated Sx: Nausea/Sweating/Dizziness/Dyspnea/Fever/Cough/Anorexia/Ankle oedema/Dysarthria
- Time and duration: Pattern; Time of day; Associated activity; Regularity/Irregularity
- Exacerbating and relieving factors: Medication/Moving/Breathing/Eating/Resting/Position/Stress
- Severity: 1-10 pain scale
How do you examine a patient presenting with chest pain?
- Intro + ID
- Consent
- Manage set-up: 45º
- End-of-bed inspection: Condition; Sweaty; Pale; SOB; Deformities/Syndromes; Fomites
- Hands: Temperature; Capillary refill; Palmar surface; Dorsal surface; Nails (clubbing)
- Head/Face: Mouth; Eyelids; Iris; Fundi
- Pulses: Radial (collapsing?); Brachial; Carotid
- Blood pressure
• JVP ± abdominojugular test
• Inspect pericardium: Deformity; Pulsations; Scars; Dilated vessels
• Palpate precordium: Heaves; Thrills
• Auscultation: A (2nd ICS RHS); P (2nd ICS LHS), T (4th ICS LHS), M (5th MCL LHS)
- Repeat with bell
- Accentuation maneuver: forward + expiration (aortic) and LHS + expiration (mitral)
• Lung bases: crackles/consolidation
- Inspect lower limbs: Temperature; Colour; Skin; Hair; Amputations; Ulcers
- Palpation: Pulses (Femoral; Popliteal; Tibialis Posterior; Dorsalis Pedis); Temperature; Capillary refill time; Peripheral oedema
- Buerger’s Test: 45º lower reactive hyperemia
- Close consultation: Thank; Explain findings; Answer questions
List the investigations needed for a patient presenting with chest pain - suspected MI.
- ECG: STEMI (ST raised ≈ < 2-2.5mm in two contiguous ECG leads)
- Glucose: Normal or elevated plasma glucose (hyperglycemia common in setting of acute MI)
- Cardiac Troponin: Elevated > 99th percentile of reference limit
- FBC: Normal range but can vary – raised CRP
- U+E: Normal but can vary – electrolyte disturbances; eGFR recorded early on
- Serum lipids: Normal or elevated
- ABG: SaO2 < 90% O2
- CXR: PE; Cardiomegaly; Pacemaker; Clear lung fields; Normal cardiac contour
- Echocardiogram: LV changes; valvular defects; RV changes; Pericardial effusion; LV mural thrombus
List the treatment of angina.
- ß-Blockers: Bisoprolol, Atenolol
- CCBs: Amlodipine, Lercanidipine; Diltiazem, Verapamil
- Nitrates: GTN, Isosorbide mononitrate
- Potassium channel activators: Nicorandil
- HCN channel blockers: Ivabradine
- Other: Ranolazine
Outline the treatment/management for MI.
- Aspirin: 300mg PO
- Anti-platelet (P2Y12 inhibitor): Clopidogrel 75mg PO OD
- Anti-emetic: Metoclopramide
- Analgesia: IV Morphine
- Oxygen: if SpO2 < 94%
- IV Nitrate (GTN)
• Coronary reperfusion therapy: PCI or Thrombolysis (streptokinase)
List the functions of the heart
- Bulk flow of materials
- Temperature regulation
- Homeostasis
- Host defense
- Reproduction
Outline the two types of circulation. State the pressures in each system.
1) Pulmonary: RH to lungs - PSP: 30mmHg - PDP: 12mmHg
2) Systemic: LH to rest of body - SBP: 120mmHg - DBP: 70mmHg
List the surfaces of the heart and what they are composed of.
- Anterior (sternocostal): RV + RA + LV
- Inferior (diaphragmatic): RV + LV - Separated from base by coronary sinus
- Base (posterior): LA
List the borders of the heart and what they are composed of.
- Right margin (R pulmonary): RA
- Left margin (L pulmonary): LV + left auricle - Cardiac impression in L lung
- Inferior margin: RV + LV
State the four corners of the heart in each costal cartilage.
- R 3rd CC
- R 6th CC
- L 2nd CC
- L 5th CC
Concept: LA –> RV: 2, 3, 5, 6
Outline the embryological formation of the heart and its sinuses.
- Heart tube folds in embryological development
- Invaginates into serous pericardium with outer fibrous sac
- Ventral looping
- Sinus formation (Transverse sinus: arteriovenous plane; Oblique: potential space posterior to LA)
List 5 features of the Right Atrium.
- SVC + IVC + CS + smallest cardiac vein opens into
- Atrium proper (smooth surface)
- Right auricle (ridges)
- Crista terminalis: separates RA from R Auricle from SVC and IVC opening
- Limbus of fossa ovalis: RHS of IA septum ≈ site of foramen ovale
- Pectinate muscles: ridged inner surface ≈ power for contraction w/o thickening cardiac wall
- Tricuspid AV valve: 3 cusps, base of each cusp attached to annulus fibrosus ≈ blood flows forward and medially through valve
List 5 features of the Left Atrium.
- Pulmonary veins x4 open into
- Atrium proper (smooth surface)
- Left Auricle (ridges)
- Pectinate muscles: ridged inner surface ≈ power for contraction w/o thickening cardiac wall
- Falx septi: depressed area on LHS of IA septum by fusion of valve of foramen ovale
- Mitral (bicuspid valve): 2 cusps with base of each valve attached to annulus fibrosus; blood flows towards apex of heart
List 5 features of the right ventricle.
- Pulmonary valve: 3 semilunar cusps - on free edge, nodule of semilunar cusp ≈ each cusp has pulmonary sinus ≈ helps closure of pulmonary valves after systole
- Chorda tendinea: fibrous cords extending between papillary muscles + AV cusps ≈ prevent exertion of cusps ≈ prevent regurgitation of blood into atria during ventricular systole; one papillary muscle to more than one cusp
- Papillary muscles: 3 ≈ attaching to chorda tendinea attaching to cusps; named relative to position (anterior, posterior and septal)
- Trabecula carnea: irregular muscular ridges ≈ thick, course, muscular bundles
- Septomarginal trabecula (moderator band): bridge between IV s eptum + anterior papillary muscle ≈ carry R Bundle branch of AV bundle of cardiac conduction system ≈ passes from septum to base of anterior pituitary muscle ≈ contractile impulses reach ≈ contract in synchrony
- Infundibulum (conus arteriosus): leads to pulmonary trunk ≈ blood flows upwards, backwards and to the left through this valve ≈ promotes laminar flow
List 5 features of the left ventricle.
- Trabecula carneae: irregular muscular ridges
- Papillary muscles: 2 ≈ attaching to chorda tendinea attaching to cusps; named relative to position (anterolateral and posteromedial)
- Chorda tendinea: fibrous cords extending between papillary muscles + AV cusps ≈ prevent exertion of cusps ≈ prevent regurgitation of blood into atria during ventricular systole; one papillary muscle to more than one cusp
- Aortic valve: 3 semilunar cusps ≈ ≈ superior surfaces of cusps and aortic wall bear aortic sinuses ≈ origination for coronary arteries
- Aortic vestibule: leads to aorta ≈ blood flows upwards, backwards and to the right ≈ laminar flow
List 3 veins opening into the Right Atrium.
- Superior Vena Cava: R 3rd CC and sternum; Avalvular; intervenous tubercle (black)
- Inferior Vena Cava: Valve of IVC (X retrograde flow)
- Cardiac Sinus: Valve of CS (= X retrograde flow)
Outline the fibrous skeleton of the heart. Give 3 functions of the fibrous skeleton.
- Fibrous ring with connecting areas structural + functional support
- 4 rings (= annulus fibrosus) surround valves
- 2 trigones (R+L) between four rings and membranous portions of IA, IV and AV septa
Functions of fibrous skeleton:
• Cusp attachment
• O+I for atrial and ventricular muscles
• Insulate atria from ventricles independent atrial and ventricular contractions
List and outline the 3 layers of the cardiac wall.
1) Endocardium
• Endothelium
• Line inner surfaces and valves
• Oxygenated directly from blood in chambers
2) Myocardium
• Spiral and circular muscle fibres
• Originate and insert into fibrous skeleton (annulus fibrosus + trigones)
• Atrial musculature –> pectinate muscles
• Ventricular musculature –> trabeculae carneae, papillary muscles + septomarginal trabeculae
3) Epicardium
• Visceral layer of serous pericardium
Outline the heart sounds.
- S1: 1st heart sound –> closure of AV valves at systole
* S2: 2nd heart sound –> closure of semilunar valves at diastole
Outline the surface projection of the valves.
- Aortic Valve: R 3rd ICS
- Pulmonary Valve: L 3rd ICS
- Tricuspid Valve: R 4th ICS
- Mitral valve: R 4th CC
Outline the regions for cardiac auscultation.
- Aortic valve: 2nd R ICS for S2
- Pulmonary valve: 2nd L ICS for S2
- Tricuspid valve: 4th L ICS for S1
- Mitral valve: 5th L ICS for S1
Outline the blood supply to the heart.
Arterial: 1. Right Coronary Artery: RA, RV, SAN, AVN, IV septum, small areas of LA and LV • SA Nodal branch • Right marginal artery • Posterior interventricular artery • AV Nodal branch
Anastomoses with Left Coronary Artery in coronary sulcus and apex
2. Left Coronary Artery: LA, LV, IV septum • Left Anterior Descending Artery (LAD) • Left Marginal Artery • Left Diagonal Branch • Circumflex Artery
Anastomoses with Left Coronary Artery in coronary sulcus and apex
Concept: RCA usually ‘dominant’ forming posterior part of interventricular septum
Outline the venous drainage of the myocardium.
- Coronary Sinus: Receives cardiac venous blood; located in the AV groove; Thebesian valve at joining of right atrium
- Great Cardiac Vein (Anterior interventricular vein): Drain anterior LV + RV
- Left Marginal Veins: Drain left ventricle into Great Cardiac Vein or Coronary Sinus
- Inferior Veins of Left Ventricle (Posterior veins): Drain left ventricle
- Middle Cardiac Vein (Posterior interventricular vein): Drains posterior LV + RV draining into Coronary Sinus or directly to Right Atrium
- Small Cardiac Vein (Right Cardiac Vein): Drains right ventricle
What mnemonic can be used to remember the pairings of the heart.
- Great-Lad: Great Cardiac Vein + Left Anterior Descending (LAD) Artery
- Mid-Post: Middle Cardiac Vein + Posterior Interventricular Artery
- Small-Margins: Small Cardiac Vein + Right Marginal Artery
Outline the cardiac conduction system.
• SAN: anterior to SVC opening, superior to crista terminalis
• AVN: postern-inferior part of IA septum, close to opening of coronary sinus
• AV Bundle/ BoH: Runs along membranous part of IV septum + conductive route through the fibrous skeleton
• R+L Bundle Branches:
i) Right Bundle Branch: Descends on RHS of IV septum ≈ enters septomarginal trabecula to reach base of anterior papillary muscle ≈ splits into Purkinje fibres spreading out into ventricular walls
ii) Left Bundle Branch: Descends on left side of membranous part of IV septum ≈ splits into Purkinje fibres
Outline the innervation of the heart.
• Presynaptic sympathetic fibres T1-5
- Increase chronotropy + inotropy
- Dilate coronary arteries
• Parasympathetic fibres from Vagus Nerve (CN X)
- Decrease chronotropy + inotropy
- Vasoconstriction of coronary arteries
List 3 shunts in prenatal circulation.
1) Hepatic circulation:
• Ductus venosus –> Ligamentum venosum
2) Pulmonary circulation
• Foramen ovale –> Limbus of fossa ovale/falx septi
• Ductus arteriosus –> ligamentum arteriosum
Outline the cellular process of cardiac muscle contraction.
Cellular Processes • Action potential • L-type DHP channels open (CaVg) • Ca2+ influx = calcium spark • Calcium binds RyR on SR • Calcium released in Calcium-induced Calcium Release (CICR) • Binds Tpn-C • Reveals binding site on actin • Cross-bridge cycling
Concept: Maximum inotropy achieved by SNS input
Outline how the SNS modified cardiac muscle contraction at the cellular level.
SNS modification: Catecholamines ≈ ß1 adrenoceptor ≈ Gas ≈ cAMP ≈ PKA ≈ increase calcium from SR and increased calcium stores
- A) +Pi to sarcolemmal Ca2+ channel (via protein kinase) ≈ release more Ca2+ from SR
- B) +Pi to phospholamban –> reduce inhibition of SR Ca2+-ATPase ≈ sequestration increased for higher cytosolic release of calcium
Outline the cellular effect cardiac glycosides have on cardiac muscle contraction.
- Inhibit Na,K-ATPase
- Reduced Na+ extrusion
- Na+ accumulation
- Reduced electrochemical gradient for Ca2+ to diffuse into
- Less extracellular calcium
- IC Ca2+ and Na+ accumulation
- After-depolarisations arrhythmias
List the 3 types of refractory period.
- Absolute Refractory Period (ARP): all NaVg inactivated ≈ no stimuli can trigger AP
- Relative Refractory Period (RRP): most NaVg inactivated, some NaVg able to be depolarised ≈ high magnitude stimuli can trigger AP
- Supernormal Period (SNP): majority of NaVg been depolarised but not at low enough levels to return to resting membrane potential ≈ if another AP propagates across cell, increased % that AP occurs
Outline the order of the cardiac cycle.
1) Atrial systole
2) Isovolumic contraction
3) Ventricular contraction
4) Isovolumic relaxation
5) Ventricular diastole
Outline the key stages in atrial systole. Include pressure, volume, ECG and sounds.
- Increase atrial, ventricular and venous pressure
- Increase ventricular volume
- Blood can move retrograde due to no venae cavae valves however inertia of anterograde flowing venous return reduces retrograde flow
ECG: P wave ≈ atrial depolarisation ≈ contraction
Pressure: Atria contract to empty following initial pressure gradient-driven atria to ventricle diastole ≈ complete ventricular filling as blood passes through tricuspid AV valve into ventricles
• Atrial P > ventricle P ≈ blood filling
• Compliant ventricles ≈ fill ≈ increase volume without increase P ≈ compliance
• Atrial contraction ≈ reduced compliance and ventricular P increases
Volume: Ventricle volume increases
• 20-25% blood at rest ejected from atria and into ventricles
• Final ventricular volume topped up by atrial contraction
Phonocardiogram: S4 ≈ atrial gallop - LV non-compliant and blood strikes LV
Outline the key stages in isovolumic contraction. Include pressure, volume, ECG and sounds.
= phase between ventricular systole and opening of semilunar valves
- Ventricular pressure rises without a change in volume ≈ isovolumic ≈ ventricular volume remains constant in brief period
ECG: R wave on ECG Pressure: Earliest rise in ventricular pressure following atrial contraction
Volume: Remains the same
Phonocardiogram: S1 - AV valves shut
Outline the key stages in ventricular contraction (ejection). Include pressure, volume, ECG and sounds.
- Opening semilunar valves marks onset
- Divided into: rapid ejection (shorter phase) + reduced ejection (longer phase) - Following reduced ejection period, flow decelerates due to pressure gradient reversal ≈ three waves of venous return: a wave (atrial contraction); c wave (impact of common carotid artery with jugular vein + closure of tricuspid in early ventricular systole); v wave (rise in pressure due to atrial filling)
ECG: QRS complex ≈ ventricular depolarisation (rapid ejection) + T wave (reduced ejection)
Pressure: Sharp rise in pressure + gradual rise in pressure
- Sharp rise in ventricular + aortic pressure ≈ peak ventricular and aortic pressure
- TPR > ventricular pressure ≈ reduced ejection period
Volume: Rapid decrease in ventricular volume
- Reduced ventricular volume ≈ increased aortic blood flow
- Sharp decrease in atrial pressure at onset of ventricular election from descent of base of heart + consequent stretching of atria
- Peak flow curve coincided with left pressure curve intersecting aortic pressure in ejection
- Reversal of ventricular-aortic pressure gradient in presence of continuous blood flow from LV to aorta is result of potential energy stored in stretched atrial walls ≈ decelerate blood flow from LV to aorta
Phonocardiogram: S2 ≈ closure of aortic + pulmonary valves
Outline the key stages in isovolumic relaxation. Include pressure, volume, ECG and sounds.
= Period of time between closure of semilunar valves and opening of AV valves ≈ major fall in ventricular pressure without change in ventricular volume
ECG: TP segment ≈ baseline ≈ reference to ST segment election or depression
Pressure: Major fall in pressure
Volume: No change in volume
Phonocardiogram: None
Outline the key stages in Ventricular diastole. Include pressure, volume, ECG and sounds.
- Ventricular filling after opening of AV valves
- Atrial P > ventricular P ≈ blood flows down pressure gradient into relaxing ventricles ≈ rapid filling phase
ECG: TP segment ≈ baseline ≈ reference to ST segment elevation or depression
Pressure: Decrease in ventricular pressure below left atrial pressure
- Pressure reversal ≈ open mitral valve + tricuspid valve ≈ rapid flow of blood from atria to relaxing ventricles ≈ transient decrease in atrial + ventricular pressure + sharp increase in ventricular volume
Volume: Increase in volume
- Increase in blood flow due to pressure reversal ≈ atrial P > ventricular P ≈ open mitral + tricuspid valve ≈ flow of blood from atria to relaxing ventricles
- Slight increase during diastasis as blood returns from peripheral veins + lungs ≈ slow addition to ventricular filling shown by gradual rise in atrial, ventricular and venous pressure and ventricular volume
Phonocardiogram: S3 ≈ ventricular gallop
- Mitral valve opens ≈ passive filling of left ventricle ≈ large amount of blood striking compliant left ventricle
Give the equation for Cardiac Output.
• Cardiac Output (CO) = Strove Volume (SV) x Heart Rate (HR)
Which two variables contribute to CO? Name at least two factors contributing to each of the two variables.
- SV: EDV (Pre-Load: Venous return + Filling Time); ESV (Pre-load: Venous return + filling time; Contractility (ANS); Afterload (Vasodilation)
- HR: SNS; PSNS; Hormones; Drugs
What is stroke volume?
• Stroke volume is the ejection fraction (volume of blood) pumped by the left ventricle of the heart in one contraction
State the equation for SV.
• Stroke Volume (SV) = End-Diastolic Volume (EDV) – End-systolic Volume (ESV)
Give the two categories of mechanism controlling stroke volume. Outline the main mechanism in each and give the volume changes.
1) Intrinsic: F-S Mechanism • Increased EDV • Increased length-tension relationship • Increased inotropy • EDV increased (increased lusitropy too)
2) Extrinsic: SNS • Sympathetic discharge of NA • Increased chronotropy • Reduced filling with EDV • Reduced ESV • SV increased
List and outline factors contributing to stroke volume.
- EDV (‘pre-load’)
• Venous return (increased load -> stretch sarcomeres to optimal 2.2um -> force of contraction -> increased/optimal inotropy)
• Filling time
• -> ‘Pre-load’ = initial stretching of cardiac myocytes prior to contraction - ESV
• Pre-load: Venous return + Filling time
• Contractility (ANS)
List 3 factors contributing to venous return.
- SNS drive: ∆ vasculature + veins (arterial pulse pump) -> ∆ capacity -> increase venous return -> increase CO
- Muscle pumps: Contractions -> open valves
- Inspiration -> Diaphragm descends -> increased intraabdominal pressure + reduced intrathoracic pressure -> reduced pressure in intrathoracic veins + increased pressure in intraabdominal veins -> increased pressure difference -> increased venous return
- Blood volume: Increased blood volume -> increased venous return
Outline the Frank-Starling mechanism.
Frank-Starling Mechanism
= Length-tension relationship of cardiomyocyte sarcomeres which yields a pressure-volume curve shown in cardiac muscle.
Principle: • Increased EDV (pre-load) • Increased sarcomere stretching • Sarcomeres form optimal cross-bridge • Optimal inotropy
Outline the mechanism and influence of the divisions of the ANS on chronotropy and inotropy
1) SNS • NA binds ß1 adrenoceptors • Gas • cAMP • PKA • +Pi 1) Phospholamban (reduce extrusion) + 2) Ca2+-ATPase + CaVg (increase calcium spark) • Increased IC [Ca2+] • Increased chronotropy + inotropy + lusitropy
2) PSNS • ACh binds M2R • Gai • Reduced cAMP • Negative chronotropic + inotropic effects
Outline how Fick’s Law can relate to Cardiac Output.
- Cardiac Output provides oxygenated blood into systemic circulation for Gaseous Exchange via Diffusion outlined by Fick’s Law
- CO = VO2 / (Ca-Cv)
- VO2: Volume of oxygen consumed per minute
- Ca: Oxygen content of arterial blood
- Cv: Oxygen content of venous blood
Principle
• Cardiac Output (L/min) = Rate of O2 consumption (L/min) (VO2/Ca-Cv)
Outline the relationship between arterial compliance and pulse pressure.
- Inversely proportional
- Decreased compliance -> reduced change of volume/pressure -> stiffer -> increase in systolic pressure + decrease in diastolic pressure -> Increased Pulse Pressure
Outline how stroke volume influences pulse pressure.
- Proportional
- Increase stroke volume -> blood volume ejected (SV (EF) = EDV – ESV) -> increased systolic pressure (exceeds runoff doubled) + diastolic pressure falls at same rate -> pressure drops to higher than previous DBP -> new SBP – DBP»_space;
State the equation for mean arterial blood pressure.
• MABP = DBP + 1/3 PP
Outline the changes, if any, to mean arterial blood pressure in exercise.
- MABP is Constant in Exercise (homeostasis): increased CO + reduced SVR (TPR)
- Increased HR + SV = increased CO
Outline how to measure blood pressure.
- Inflate cuff
- Occlusion of brachial artery no sound
- Begin deflating cuff
- Listen to sound at cubital fossa
- Pressure taken at First Korotkoff Sound (SBP)
- Pressure taken when no sound laminar flow Fifth Korotkoff Sound (DBP)
State 2 factors which may falsely elevate BP.
- Age: ATHSCL; Calcification ≈ Reduced compliance
- Cuff size: narrow ≈ false elevation. 80/40 rule ≈ Length should be 80% circumference of upper arm and Width 40% of upper arm circumference
Outline how central blood volume changes cardiac output.
• Central blood volume increased ≈ increase venous return ≈ increase EDV ≈ F-S Mechanism ≈ increase CO
List two broad events which change central blood volume. Give ways this can be achieved.
• Change in total blood volume
+ Salt retention
+ Shift in fluid from interstitial space to plasma
- Haemorrhage
- Fluid loss
- Transfer of fluid from plasma to interstitial space
• Change in distribution of blood volume
+ Transmural P
+ Venous compliance
What is a murmur?
• Abnormal valve, septal defect or outflow obstruction ≈ turbulent flow ≈ heard on auscultation
What is an innocent murmur? Give three patient groups which may display this.
• Innocent murmur: turbulent blood flow due to increased velocity of blood
- Athletes
- Febrile patients
- Pregnant women
Outline the S1 heart sound.
- Closure of atrioventricular valves
- Atrial pressure increases ≈ final contraction of 20% volume into ventricles ≈ ventricular pressure rises slightly due to increased volume but also mitigated by compliance ≈ Atrial pressure > Ventricular pressure ≈ AV valves close
- S1 sound ≈ Lub
Outline the S2 heart sound.
- Closure of semilunar valves
- Ventricular pressure increases ≈ contraction ≈ 120mmHg ≈ semilunar valves open as ventricular P > outflow vessel P ≈ reduced volume and pressure in contraction ≈ outflow P (pulmonary artery and aorta) > ventricular P ≈ semilunar valves close
- S2 ≈ Dub
What thinking process can be used to identify the type of murmur.
Think of which valves are opened in normal cardiac cycle
• S1 (mitral and tricuspid valves shut thus turbulent from from regurgitation or from stenosis of outflow valves)
• S2 (aortic and pulmonary outflow valves shut thus turbulent flow from regurgitation or from stenosis of AV valves mitral and tricuspid)
In a systolic murmur, what phase does this occur. Which valves can be implicated and the which types of murmur may bepresent?
Systole
Open:
• Aortic stenosis
• Pulmonary stenosis
Closed:
• Mitral regurgitation
• Tricuspid regurgitation
In a diastolic murmur, what phase does this occur. Which valves can be implicated and the which types of murmur may bepresent?
Diastole
Open:
• Mitral stenosis
• Tricuspid stenosis
Closed:
• Aortic regurgitation
• Pulmonary regurgitation
List 3 risk factors for aortic stenosis.
- Older age
- Congenital abnormalities: subvalvular; valvular (Bicuspid); Supravalvular
- Rheumatic fever
- CKD/HTN
List the aetiology for aortic stenosis.
- Calcification (Aortic sclerosis to severe Aortic Stenosis)
- Smoking
- Hypertension
- Diabetes
- Dyslipidaemia
- Elevated CRP (inflammatory conditions)
- Rheumatic Fever
• Congenital (bicuspid valves): subvalvular; valvular (bicuspid); supravalvular (Williams Syndrome)
Outline the pathophysiology of aortic stenosis?
: Damaging stimuli ≈ inflammatory processes ≈ valvular endocardium damaged ≈ Abnormal blood flow across valve + Narrowing of aortic valve ≈ increased afterload ≈ failure to increase CO on demand ≈ LV HCM ≈ increased myocardial O2 requirement ≈ reduced systemic and coronary flow ≈ reduced myocardial oxygen delivery
List the symptoms a patient with an aortic stenosis may exhibit.
- SOBE
- Dyspnoea
- Cx Pain
- Exertional presyncope
- Insidious onset
List the examination findings present in a patient with aortic stenosis.
- Ejection systolic murmur: crescendo-decrescendo pattern; radiates to carotid; loudest at 2nd ICS RHS (aortic valve auscultation point) and expiration (RILES)
- S2 diminished (advanced AS)
- Heavy apex beat
- Narrow pulse pressure: reduced SBP and DBP remains = ∆PP
- Paradoxically split S2 (severe AS, aortic valve so delayed it follows pulmonic valve closure in expiration)
- Gallavardin’s Phenomenon: holosystolic murmur at apex of heart occurring in older patients with calcific AS; mimics mitral regurgitation
List the investigations ordered in a patient with suspected aortic stenosis
- ECG: QRS amplitude increased – LV hypertrophy
- CXR: Cardiomegaly; Pulmonary oedema (air space opacification, Bat-wing distribution, Kerley B lines
- Echocardiogram: Stiff leaflets; Retrograde flow (Doppler); Bernoulli Equation
Outline which Equation can be used via US imaging modality to calculate pressure changes in aortic stenosis.
Bernoulli Equation:
∆P = 4 (V22 - V12)
If V1 < 1.5..
∆P = 4v2
E.g. V1 = 1 cf V2 = 4 thus use ∆P = 4v2 = ∆P = 4(4)2 = 64mmHg
State the categories of AS and their criteria.
- Mild < 35mmHg
- Moderate: 36-64mmHg
- Severe > 65mmHg
List the management for aortic stenosis.
Pick and Select dependent on Clinically Stable Asymptomatic; Clinically Stable Symptomatic or Clinically Unstable
• Echocardiogram: Follow up in 1-5 years
• Medicine withdrawal: Vasodilators which exacerbate peak pressure gradient – Nitrates, CCBs, Nicorandil, ACEi, ARBs, Alpha-blockers, Phosphodiesterase inhibitors
• Surgical Valve Replacement
- ABX for infective endocarditis prophylaxis
- Anticoagulation
• TAVR
- ABX for infective endocarditis prophylaxis
- Anticoagulation
List 3 risk factors for aortic regurgitation.
- Bicuspid aortic valve
- Rheumatic fever
- Endocarditis
- Connective tissue diseases
- Aortitis
What is the aetiology of aortic regurgitation.
- Congenital: Bicuspid aortic valve
- Acquired: Valvular
- Rheumatic disease
- Degenerative
- Endocarditis
• Acquired: Supravalvular e.g. Aortic Root Dilation
- Marfan’s Syndrome
- Takayasu’s
- Aortitis secondary to syphilis
• Acquired: Traumatic
Outline the pathophysiology of aortic regurgitation.
• Change to valvular function ≈ retrograde flow of blood ≈ increase in left ventricular volume + pressure ≈ increase wall tension (Laplace’s Law: T = PR) ≈ hypertrophy (eccentric hypertrophy >) ≈ systolic hypertension 2º to increased stroke volume ≈ volume overload causes increase in left ventricular end-diastolic volume ≈ increase cavity size ≈ systolic dysfunction
List the symptoms experienced by a patient with aortic regurgitation.
- Dyspnoea (SOBE)
- Fatigue
- Weakness
- Orthopnoea
- Paroxysmal Nocturnal Dyspnoea
- Ankle oedema
List the examination findings of a patient with aortic regurgitation.
- Ankle oedema
- Soft S1: Early coaptation of mitral valve leaflets
- Soft or absent S2
- Early diastolic murmur; high pitched; heard at 2nd RHS ICS loudest on expiration
- Displaced apex beat
Outline the investigations requested in a suspected case of aortic regurgitation.
- ECG – non-specific but routine and check for myogenic cause
- CXR: Cardiomegaly; Pulmonary Oedema
- Echocardiogram: Jet of regurgitation, mixed jet stream
How would you manage an aortic regurgitation?
- Annual Follow Up
- BP management (minimise dilation): inotropes (dobutamine or dopamine) + vasodilators (nitroprusside)
- Surgical Valve Replacement
- TAVR
List the risk factors for mitral stenosis.
- Streptococcal infection
* Female sex
List the aetiology for mitral stenosis.
- Rheumatic fever (95%)
- SLE
- Serotogenic drugs (e.g. Fenfluramine)
- Ageing (Mitral annular calcification)
- Amyloidosis
- Chest radiation
• Congenital deformity: Valvular/Subvalvular
Outline the pathophysiology of mitral stenosis.
Damage ≈ damage to valvular endocardium ≈ inflammatory processes ≈ fibrosis/calcification of valves ≈ reduce valve orifice ≈ increased LA pressure (referred to lungs) + reduced LV filling reducing cardiac output
1) Increased LA pressure ≈ dilated LA (compliance) ≈ increased pulmonary venous pressure ≈ pulmonary congestion
2) Reduced LV filling pressure ≈ reduced cardiac output
List the symptoms of a patient with mitral stenosis.
- Dyspnoea
- Ankle oedema
- Orthopnoea
- Paroxysmal Nocturnal Dyspnoea
- Atrial fibrillation
List the examination findings of a patient with mitral stenosis.
- Raised JVP (pulmonary HTN or RV failure)
- Atrial fibrillation
- Low-pitched rumbling apical mid-diastolic murmur (MDM): heard best 5th ICS MCL LHS, expiration (RILEs)
- Absence of silence between S1-S2
Outline the investigations and findings in a patient with mitral stenosis.
- ECG: AF, P mitrale (bifid P wave in lead II, upright P waves in lead I)
- CXR: LA enlargement (sail sign), pulmonary oedema
- Echocardiogram: Thick mitral valve (X Fishmouth view); lack of movement; small valvular orifice
Outline the management for a patient with mitral stenosis.
• Follow-up annually
- ß-blockers
- Cardiac glycosides (Digoxin)
- Anticoagulants (DOACs, anti-platelets, anti-coagulants
- Surgical mitral valve replacement
- Percutaneous Balloon Valvuloplasty (via Femoral Vein)
List the 3 risk factors for mitral regurgitation.
- Mitral valve prolapse
- Rheumatic disease
- Infective endocarditis
- PMHx: MI, CHD, Ischaemic Heart Disease
- HOCM
- Drug abuse (anorectic drugs/dopaminergic drugs)
List the 3 aetiological features in the pathogenesis of mitral regurgitation.
- Rheumatic Fever
- Infective endocarditis
- Ischaemic papillary muscle dysfunction
- Myxomatous prolapse
- Prolapse
• Congenital: Congenital mitral stenosis (rare***)
Outline the pathophysiology of mitral regurgitation.
Damage to valvular endocardium or myocardium ≈ inflammatory process ≈ failure of mitral valve to close in S1 sound due to patency ≈ regurgitation from LV to LA in systole ≈ dilation of LA + eccentric cardiac (functional) hypertrophy ≈ increase SV to maintain CO ≈ time ≈ LV dysfunction and increased LV end-systolic diameter
List 3 symptoms which a patient may present with if they have mitral regurgitation.
- Dyspnoea (SOBE)
- Ankle oedema
- Orthopnoea
List 3 signs a patient with mitral regurgitation may have.
- Atrial Fibrillation
- Displaced apex beat
- Pan-systolic murmur (S1-S2): loudest at 5th ICS MCL LHS in expiration radiating to axilla
Outline 3 investigations you may order in a patient with mitral regurgitation. Give any relevant findings.
- ECG: AF, P mitrale (bifid P wave in lead II, upright P waves in lead I)
- CXR: LA enlargement (sail sign), pulmonary oedema
- Echocardiogram: ∆ leaflet structure; regurgitation (jet stream)
Outline the treatment for a patient with mitral regurgitation.
• Annual follow-up
- Diuretics
- ACEi/ARBs
- Nitrates: Nitroprusside
- Ionotropic agents: Dobutamine/Dopamine
- Surgical mitral valve repair
- Mitral Valve Replacement
- TMVR
- Mitraclip procedure
List 3 risk factors for tricuspid regurgitation.
- Rheumatic fever
- Left-sided heart failure
- Permanent pacemaker
List 3 aetiological features involved in the pathogenesis of tricuspid regurgitation.
- Rheumatic Fever
- 2º RH dilatation
- 2º pulmonary hypertension
- Marfan’s Syndrome
- Tricuspid valve prolapse
• Congenital: Valvular (Cleft Valve)
Outline the pathophysiology of tricuspid regurgitation.
Damage ≈ inflammation ≈ valve is patent and following ‘closure’, allows regurgitation between S1-S2 ≈ RH dilates + elevated RA pressure ≈ Atrial Fibrillation + RV dysfunction/dilation
List 3 symptoms a patient with tricuspid regurgitation may present with.
- Fatigue
- Dyspnoea
- Peripheral Oedema
- Palpitations (Atrial Fibrillation)
List 3 signs a patient with tricuspid regurgitation may show upon examination.
- JVP raised
- RV heave
- Pan-systolic murmur: left sternal edge, loudest in inspiration
Outline the investigations you may order in a patient with tricuspid regurgitation.
- ECG: Atrial Fibrillation, P mitrale
- CXR: Cardiomegaly, pleural or pericardial effusion, pacemaker presence
- Echocardiogram: valve morphology/function, regurgitation
Outline the management you may order in a patient with tricuspid regurgitation.
- Manage underlying condition
- Heart Failure Management and Risk Factor Modification
- Surgical Valve Replacement
List 3 risk factors for tricuspid stenosis.
- Rheumatic Fever
- GAS Pharyngitis
- Metastatic carcinoid tumours
Outline two main categories for the aetiology of tricuspid stenosis.
- Rheumatic Fever (RHD)
* Congenital
Outline the pathophysiology of tricuspid stenosis.
Damage (e.g. cross-reactivity between GAS and host-valve tissue) ≈ inflammation ≈ fibrosus of annulus and chordae tendineae ≈ overlap ≈ reduced tricuspid flow into RV ≈ RA pressure increases ≈ RA dilation ≈ Increased retrograde flow into IVC, SVC and cardiac veins
List three symptoms a patient with tricuspid stenosis may present with.
- Dyspnoea
- Fatigue
- Ankle Oedema
List two examination findings you may observe in a patient with tricuspid stenosis.
- Elevated JVP (prominent A wave in sinus rhythm)
* Diastolic murmur: heard best at 4th ICS LHS and increased by inspiration (RILEs); mid-diastolic murmur
Outline the investigations you may order in a patient you suspect has tricuspid stenosis.
- ECG: Sinus Rhythm vs Atrial Fibrillation
- CXR: RA enlargement, pulmonary opacities
- Echocardiogram: Elevated tricuspid valve gradient, reduced flow
Outline the management for tricuspid stenosis.
- Annual Follow-Up
- Surgical Tricuspid Valve Replacement
- Percutaneous Balloon Valvuloplasty
List 3 risk factors for pulmonary regurgitation.
- Congenital heart disease
- Pulmonary stenosis/Valvuloplasty
- PMHx endocarditis/Rheumatic Fever/Carcinoid Heart Disease
List 3 aetiological features contributing to the pathogenesis of pulmonary regurgitation.
• Congenital heart disease (Majority): ToF
- Left-sided heart failure e.g. Mitral Valve Stenosis
- Rheumatic Fever
- Endocarditis
- Carcinoid Heart Disease
- Syphilis
- Trauma
Outline the pathophysiology of pulmonary regurgitation.
Damage to valves ≈ patency ≈ volume overload in RV ≈ Dilation of RV + RV hypertrophy ≈ Equalisation of pulmonary artery pressure and RV pressure in diastole ≈ RV failure with RHS SV reduced ≈ Reduced oxygenation of blood ≈ Oedema, dyspnoea, fatigue
List 2 symptoms you may expect a patient to present with if they have an underlying pulmonary regurgitation.
- Dyspnoea
- Fatigue
- Dizziness
- Palpitations
- Syncope
- Cyanosis
List 2 examinational findings you may observe in a patient with pulmonary regurgitation.
- RV heave
* Low-pitched diastolic murmur: heart best at 4th ICS LHS on inspiration (RILEs) and sat forward
Outline the investigations you may wish to order following a finding of a low-pitched diastolic murmur heard best at the 2nd ICS LHS on Inspiration in a suspected pulmonary regurgitation patient.
- ECG: Non-specific
- CXR: pulmonary artery dilation; RV dilation
- Echocardiogram: regurgitant jet; RV dilation
Outline the treatment of a patient with pulmonary regurgitation.
- Medical Management of Heart Failure
* Surgical valve replacement
List 3 aetiological causes in the pathogenesis of pulmonary stenosis.
- Rheumatic Fever
- Endocarditis
- Carcinoid disease of the Heart
• Congenital (majority)
Outline the pathophysiology of pulmonary stenosis.
Damage ≈ inflammation/structural change ≈ reduced valve orifice ≈ reduced blood flow from RV to pulmonary artery ≈ increased ESV in RV ≈ RV hypertrophy (concentric and eccentric hypertrophy)
List three symptoms a patient with pulmonary stenosis may present with.
- Chest pain
- Syncope
- Fatigue
- Dyspnoea
List 3 examination findings you may observe in a patient with pulmonary stenosis.
- RV heave
- Systolic thrill
- Ejection Systolic Murmur: Loudest in inspiration + sitting forward at 2nd ICS LHS
- Harsh ejection systolic murmur
Outline any investigations you may wish to order in a patient where you have heard an ejection systolic murmur loudest in inspiration at the L 2nd ICS which is accentuated by expiration. Give the heart condition you think the patient may have.
- ECG
- CXR: RV dilatation
- Echocardiogram: Reduced flow through valve; valve damage/structural changes
Pulmonary stenosis
List 2 heart murmurs which are an ejection systolic murmur. Which group of patients may an ejection systolic murmur be physiological in?
Aortic sclerosis/stenosis
Pulmonary stenosis
Patient group:
- Pregnancy
- Fever
- Athletes
Give two murmurs which may be heard as early diastolic murmurs with a decrescendo sound.
Aortic regurgitation
Pulmonary regurgitation
List 4 conditions which may give a pansystolic murmur.
Mitral regurgitation
Tricuspid regurgitation
Ventricular septal defect
Mitral prolapse
Give two conditions which may give a mid-diastolic murmur.
Mitral stenosis
Pulmonary stenosis
Outline the general process of a surgical valve replacement.
- General Anaesthetic
* Midline sternotomy
List 5 negatives of a surgical valve replacement.
- LOS
- Mortality risk
- Morbidity risk
- CVI
- MI
- Haemorrhage
- Infection
- Pacemaker
- Renal failure
- Infective endocarditis
- Regurgitation
- Stenosis
Outline the process of a TAVR. What are the indications?
- Biological tissue valve: Attached to mesh framework scaffold
- Percutaneous or transapical approach
• Indications: Elderly, Frail, Major comorbidities, Risk of Surgery
List 2 advantages and 2 disadvantages of TAVR.
Advantages:
+ Minimally-invasive
+ Lower risk
Disadvantage:
- New technique
- Longevity: Unknown
Compare and contrast the benefits and drawbacks of a mechanical prosthesis vs bioprosthesis for a valve replacement.
Mechanical Prosthesis
• Longevity
• Lower risk of needing repeat surgery
- Anticoagulation mandatory
- No option for percutaneous intervention in future
Bioprosthesis
• No anticoagulation required
• Option for percutaneous intervention in future
- Higher risk of repeat surgery
- Less longevity
List 4 common congenital defects of the heart.
1) Bicuspid Aortic Valve: Bicuspid, X tricuspid semilunar
2) Atrial Septal Defect: Interatrial septum patent
3) Ventricular Septal Defect: Interventricular septum patent
4) Tetralogy of Falot
Outline the pathophysiology of a bicuspid aortic valve.
Turbulent flow ≈ valve thickening + stiffening ≈ valvular dysfunction (earlier cf degenerative aortic valve disease)
Outline the general treatment of bicuspid aortic valve
- Passive management
- AVR - TAVI
- Aortic surgery
Outline the pathophysiology of atrial septal defect.
Interatrial septum patent ≈ L atrium P > R atrium P ≈ L to R shunt ≈ reduced efficiency of CO ≈ RH pressure increases ≈ RH dilatation ≈ SOBE, dyspnoea etc
Outline the general treatment of an atrial septal defect.
- Surgical closure
- Percutaneous closure
Outline the pathophysiology of a ventricular septal defect.
Interventricular defect ≈ LV P > RV P ≈ L to R shunt ≈ recirculation of oxygenated blood ≈ RV dilatation + LV hypertrophy
Outline the general treatment of a ventricular septal defect.
- Surgical closure
- Percutaneous closure
Outline the pathophysiology of Tetralogy of Falot.
Pulmonary stenosis, RV hypertrophy, overriding aorta and Ventricular septal defect ≈ constriction of blood outflow tracts + heart working harder ≈ HCM ≈ poor systemic oxygen delivery ≈ intermittent cyanosis (infants), tetralogy spells: cyanotic, sleepy (unresponsive) and irritable ≈ relieved by squatting
List 3 symptoms a patient with ToF may experience.
- Tetralogy spells
- Cyanotic
- Tired
- Irritable
Outline the treatment for ToF.
Transannular patch
Outline the pathophysiology of Coarctation of the Aorta.
Stenosis of descending aorta ≈ reduced flow to descending aorta + systemic circulation
List 3 long-term complications of adult congenital heart disease.
1) Valve Dysfunction
2) Ventricular Dysfunction
3) Arrhythmias
Outline the options for treatment for each of the 3 potential long-term complications of adult congenital heart disease.
1) Valve
• Surgical Replacement
• TVR
• Valvuloplasty
2) Ventricular Dysfunction
- ACEi/ARBs
- ß-blockers
- Diuretics
- Cardiac Resynchronisation Therapy: Pacemaker fitted to both ventricles or both SAN and AVN
- Left Ventricular Assist Device (LVAD): Mechanical Circulatory Component pump blood into aorta via circumventing blood outside heart
- Transplant: Replace with anatomically and physiologically functioning heart
3) Arrhythmias
• ß-blockers
• Cardiac glycosides
• Anti-arrhythmic
- Pacemakers
- Implantable Cardiac Defibrillators
- Catheter Ablation
Define haemostasis and the 3 stages.
Process to prevent and stop bleeding, to keep blood within a damaged blood vessel which involves coagulation, blood changing from a liquid to a solid (gel) which has three steps: vasoconstriction, temporary blockage by platelet plug and blood coagulation (= formation of a fibrin clot). This seals the hole until tissues are repaired.
What is an endothelial cell?
Simple squamous cells (endothelial cells) lining the interior surface of blood vessels and lymphatic vessels forming a barrier between intravascular volume in the lumen and the rest of the vessel wall
Outline the role of an endothelial cell in clotting.
Inhibit platelet aggregation ≈ Reduce haemostasis + aids haemodynamic
• Produce thrombomodulin ≈ thrombin control (+ Protein C ≈ Active Protein C ≈ inhibit VIIIa production and Va production)
• Produce heparin sulphate ≈ inhibit thrombin production
• Release enzymes to degrade platelet granule-derived molecules ≈ Thromboxane
• Prostacyclin + NO ≈ Inhibit platelet aggregation + adhesion
What is a platelet? Give:
- Origin
- Site of production
- Stimulating agent and where it is produced
- Lifespan
- Destruction
Circulating, nuclear fragment of a bone marrow megakaryocytic which functions to maintain integrity of vasculature by producing a platelet plug in the second phase of clotting when attracted by lowered prostacyclin and collagen fragments; TXA2 + serotonin from platelets ≈ vasoconstriction
- Nuclear fragments of megakaryocytes
- Produced in bone marrow
- Stimulated by Thrombopoetin (TPO) ≈ Liver produces TPO
- Circulate for 5-10 days
- 30% stored in spleen
- Destroyed by antibody-mediated macrophage phagocytosis ≈ destruction
Outline the role of platelets in coagulation in a scenario of endothelium breach.
a) Platelets in circulation
• Megakaryocytes produced in bone marrow
• Pseudopods form from megakaryocytes in endothelium
• Platelets bud off of megakaryocytic mixing with RBCs and WBCs in circulation
b) Intrinsic vessel wall damage, exposure of collagen 6, binding GP IIa-IIb + platelet plug
• Breach in endothelium wall ≈ exposes subendothelium
• Prostacyclin levels lower subendothelium cf endothelium + collagen + subendothelial molecules ≈ platelet sticking ≈ platelet plug
• Platelets bind glycoprotein receptor (Gp Ib-Ix) via von Willebrand Factor (vWF) located in association with type VI collagen microfibrils in subendothelium
• TXA2 + serotonin released from ‘activated platelets’ ≈ vasoconstriction ≈ reduce vessel lumen ≈ reduced blood flow ≈ reduced blood loss
• Increase platelets adhere to site @ GP IIa-IIb platelet receptor in combination with plasma protein fibrinogen
• Platelets reduced from aggregation + extension along endothelium by in-tact endothelium ≈ endothelial cells produce prostacyclin
• Platelets changed shape ≈ release granules from platelet cytoplasm ≈ irreversible aggregation
c) Coagulation plug
• ADP, thrombin, thromboxane A2 released ≈ recruit more platelets
• Thrombin catalyses conversion of soluble fibrinogen to fibrin ≈ stabilise platelet plug
Outline the intrinsic pathway of coagulation.
Intrinsic pathway: Initiated on exposure to negatively charged non-endothelial surface e.g. collagen
• Results in XII (+Collagen) ≈ XIIa (+ XI) ≈ XIa (+IX) ≈ IXa (+X) —> Xa
• Production of Factor Xa ≈ Convergence
- Xa (+II) ≈ IIa (Thrombin)
- IIa (+I) ≈ Ia (Fibrin)
Outline the extrinsic pathway of coagulation.
2) Extrinsic pathway: Initiated by tissue factor (TF; Factor III) • Results in VII (+ TF) ≈ VIIa • VIIa (+X) ≈ Xa • Xa (+ II) ≈ IIa (Thrombin) • IIa (+ I) -> Ia (Fibrin)
List 3 inhibitors of coagulation and give their specific role.
• Protein C: Reduce Factor Va production ≈reduce IIa production) + reduce Factor VIIIa production (≈ reduce Xa production)
- activated by thrombomodulin-thrombin complex
• Co-factor, Factor S: Produce active protein C ≈ Decreased Va and VIIa (+ reduced production)
• Antithrombin: inhibits production of Xa and IIa (thrombin IIa + Xa production from X)
• Heparin cofactor II: inhibits IIa
• Heparin: stimulates antithrombin + heparin cofactor II
What is the fibrinolytic system?
System responsible for breaking down clot after clot served purpose in haemostasis which is coordinated by a series of enzymatic reactions. Plasmin is the key driver of the fibrinolytic system.
Outline the mechanism of the fibrinolytic system.
- Plasminogen (+ tPA) –> Plasmin
* Fibrin (+ Plasmin) –> D-Dimer ± Fibrin Degradation Products (FDP)
Give two ways of measuring fibrinolysis. Which method is preferred and why?
- D-Dimer assay
* D-Dimer > FDPs as specific only to fibrin
List 5 tests to assess clotting function and coagulation.
- FBC
- PT
- APTT
- TCT
- Correction tests
Outline the ways clotting function and coagulation can be assessed. Give details of each test listed.
1) FBC: platelet count/size/granules but poor assessment of platelet function
• Platelet count
• Platelet size
2) Prothrombin Time (PT): Ca2+ + plasma (replace that removed by citrate anticoagulant) + brain thromboplastin (≈ TF) ≈ 12-15 seconds cf INR
• Extrinsic pathway
• Reproducibility
• INR Reference point
• Monitor liver function: II, VII, IX and X produced in liver
• Warfarin therapy monitoring (assess via extrinsic pathway)
3) Activated Partial Thromboplastin Test (APTT): Ca2+ + plasma + kaolin + phospholipids (replace contact factor, collagen) ≈ clotting in 25-36 seconds (more steps in the intrinsic pathway)
• Intrinsic pathway
• Standard reference point
• Monitor heparin therapy
4) Thrombin Clotting Time (TCT): Ca2+ + plasma + thrombin (common pathway) ≈ fibrin –> fibrinogen
• Common pathway
• Assess presence of fibrinogen
• Check for disseminated intravascular coagulation
5) Correction Tests: Mix patient plasma + normal plasma (50:50) –> correction occurs = patient sample deficient in factors
• Prolonged PT (>15 s) or APTT (> 36s)
A patient is losing blood rapidly. Give two types of drugs which can be used to reduce this and aid haemostasis.
1) Fresh Frozen Plasma (FFP)
• Coagulation factors in normal proportion
• Dose: 15ml/kg
• 200ml plasma from blood
• Uses: Liver disease + Severe Haemorrhage
2) Cryoprecipitate (CryoPpt): Concentrated fibrinogen (Factor I), VWF and Factor VIII
• Concentrate of Factor I, VWF and Factor VIII
• 4º C
• Uses: Haemophilia and Severe Haemorrhage
What is the main difference between Fresh Frozen Plasma and Cryoprecipitate?
1) Fresh Frozen Plasma (FFP)
• Coagulation factors in normal proportion
2) Cryoprecipitate (CryoPpt): Concentrated fibrinogen (Factor I), VWF and Factor VIII
• Concentrate of Factor I, VWF and Factor VIII
List drug categories which prevent or slow clotting.
Warfarin
Heparin
DOACs
Aspirin
Clopidogrel
Give a drug class which reduces the breakdown of a clot. Outline the MOA.
1) Tranexamic Acid: Inhibit tPA –> reduce production of plasmin –> reduced fibrin degradation
• Inhibit tPA –> no plasmin production –> no fibrin degradation
• IV or Oral
List uses of anti-fibrinolytic.
• Uses: Trauma, GI bleeding, post-operative or delivery
Give the MOA of Warfarin. How can this drug be measured.
Warfarin: Competitive inhibitor of Vitamin K epoxide + Vitamin K reductase -> prevent reduced vitamin K -> reduce production of carboxyglutamate of factors II, VII, IX and X (all hepatic produced)
• Inhibit production of reduced vitamin K
• Measure by PT (extrinsic pathway) Factor VII is key in extrinsic pathway
Give 3 uses of warfarin. Outline the positives of Warfarin use and the negatives.
• Uses: DVT, PE, Prosthetic heart valve replacement, Atrial Fibrillation
Positives:
• Cheap
• Measurable effect (INR)
• Reversible: Vitamin K or factor concentrate
Negatives: • Drug interactions • Slow onset • Unpredictable dose • Regular testing: PT • Haemorrhage risk • Narrow therapeutic window
List scenarios and substances which may increase or decrease exposure to Warfarin.
Increased exposure:
• Reduce Vitamin K: ABX
• P450 enzyme inhibition: ABX, statins, acute alcohol intake
• Platelet function ∆: Aspirin, clopidogrel, NSAIDs
Decreased exposure:
• Enzyme reduction: Rifampicin, Phenytoin, Chronic alcohol intake
• High level of vitamin K
• Cranberry juice
Outline the scoring tool used when deciding to administer Warfarin.
Scoring for risk: CHADSVASc • CHF • HTN • Age (>75) = 2 • DM • Stroke • Vascular Disease • Age (65-74) • Sex Category
Outline the MOA of Heparin. Give 3 uses of Heparin. How may heparin be monitored.
2) Heparin: Binds anti-thrombin –> reduce Xa + thrombin (IIa) generation
• Bind anti-thrombin – Reduce Xa + IIa
• Monitor with APTT or fixed dose
• Uses: DVT, PE or VTE prophylaxis
Outline the MOA of DOACs. Give the two categories of DOACs.
Inhibitors of coagulation factor II or X -> decreased factor IIa or Xa
• Inhibit X/II -> reduced amount of Xa/IIa -> reduced production of Ia (fibrin)
2 Types:
• Direct thrombin inhibitors: Dabigatran
• Xa inhibitors: Apixaban, Rivaroxaban and Edoxaban
List the benefits of DOACs and list the drawbacks of DOACs.
Benefits:
• Limited monitoring needed (renal function must be fine)
• Lower bleeding risk: Apixaban
• Effective for stroke prevention
Negatives:
• Shorter half life
• Reversal agents are expensive
Give two categories of drugs that modify platelet function.
Aspirin
Clopidogrel
Outline the MOA of aspirin as a platelet-modifying drug.
1) Aspirin ≈ Irreversible, non-selective COX-1 inhibitor ≈ competitively inhibits arachidonic acid at PGH2 synthase cyclooxygenase active site ≈ reduce formation of PGH2, PGE2 and TXA2 ≈ less platelet aggregation at endothelial surface
List the uses of aspirin as a platelet-modifying drug.
Post-TIA or Post-MI, stroke prevention in AF
Give the main side effects of aspirin.
GI bleeding risk, dyspepsia
Outline the MOA of clopidogrel. Is there a reversal agent for clopidogrel?
inhibit ADP-induced platelet aggregation ≈ anti-platelet drug
• Inhibit ADP-induced platelet aggregation
• No reversal agents so effects last for platelet lifespan ≈ 5-10 days - Can ‘reverse’ with CryoPpt + FFP but takes time
Give the uses of Clopidogrel.
• Uses e.g.: Recurrent MI prevention, ischaemic stroke, TIAs
Give a drug to help remove a clot. Outline its MOA.
1) Streptokinase or alteplase ≈ tPA ≈ increase activation of plasminogen to plasmin ≈ D-dimer and FDP products
Give the uses of streptokinase or alteplase.
Stenting and clot removal (thrombectomy) are alternative treatments
Name 3 features of typical angina
Constricting discomfort in the front of the chest, or neck, shoulders, jaw or arms
Precipitated by physical exertion
Relieved by rest or GTN within 5 minutes
What is the gold standard investigation for diagnosis of angina
CT Coronary angiography
Name 3 symptom relieving
drug classes for angina
Beta blockers
Calcium channel blockers
nitrates
Name 3 classes of drugs used for secondary prevention in angina
Aspirin
Statin
Ace-inhibitor
Beta-blocker (symptom control and prevention)
When would you consider interventional cardiology or surgery in an angina patient?
Patients who are getting angina in spite of optimal pharmacological treatment (to improve symptoms)
Patients with left main stem stenosis and/or multivessel disease (to improve prognosis)
Describe the clinical presentation of ACS
Angina pain not relieved by x2 GTN w/i 15 minutes
Pale
SOB
Nausea
Angor animi
Outline the ACS diagnostic triad.
Clinical presentation
ECG
Tpn (serial or high sensitivity)
Name 3 conditions that can present as ACS
- Unstable angina
- NSTEMI
- STEMI
What is the purpose of treatment for ACS?
Survival of patient
Minimisation of myocardial damage
What is the commonest heart valve disorder in the developed world?
Aortic stenosis
Name 3 causes of flow murmurs
- Pregnancy
- Fever
- Anaemia
- Thyrotoxicosis
- Excessive exercise
Name 6 symptoms of aortic stenosis
Fatigue
Dyspnoea(breathlessness)
Chest pain
Heart Failure
Syncope
Sudden death
Name for examination findings in aortic stenosis
Murmur right upper sternal edge.
May be quiet in advanced disease
Low amplitude slow rising pulse
Low bp – narrow pulse pressure
Prominent apex beat
Signs of cardiac decompensation (heart failure)
Name the 2 main types of aortic valves (replacement)
Mechanical
Bioprosthetic
Name 3 causes of heart failure
Valvular disease
Coronary artery disease
Hypertension
Myocarditis
Cardiomyopathy (including alcoholic)
What are the goals of heart failure treatment?
Alleviate symptoms
Delay progression
Reduce mortality.
Name four symptoms of heart failure
Paroxysmal nocturnal dyspnoea or orthopnoea.
Ankle oedema
Night cough
Dyspnoea on exertion
Name 5 signs of heart failure
Cardiomegaly
Neck vein distension (raised JVP)
Rales (crepitations, crackles)
Acute pulmonary oedema
S3 gallop rhythm
Which 2 investigations are the most specific for diagnosing heart failure
Echocardiogram
Bloods: BNP
Which of the following NYCHF is this?
‘No limitation on physical activity. Ordinary physical activity does not cause fatigue, palpitation or dyspnoea.’
A. Class II
B. Class I
C. Class III
D. Class IV
B. Class I
Which of the following NYCHF is this?
‘Slight limitation of physical activity. Comfortable on rest but at ordinary physical activity results in fatigue, palpitation or dyspnoea.’
A. Class II
B. Class I
C. Class III
D. Class IV
A. Class II
Which of the following NYCHF is this?
‘Marked limitation of physical activity. Comfortable at rest but less than ordinary activity causes fatigue, palpitation or dyspnoea.’
A. Class II
B. Class I
C. Class III
D. Class IV
C. Class III
Which of the following NYCHF is this?
‘Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased.’
A. Class II
B. Class I
C. Class III
D. Class IV
D. Class IV
Name 4 pharmacological treatments for heart failure
- Diuretics (Furosemide)
- ß-blockers
- ACEi
- ARB
- MRAs
A 55 year old man with hypertension has an estimated 10 year cardiovascular disease risk of more than 10% so is to be started on the statin therapy Simvastatin.
Which of the following is the main mechanism of action of the cholesterol-lowering statin:
A. It activates the PPAR -alpha gene transcription factors that control lipoprotein metabolism, resulting in a reduction in LDL-cholesterol
B. It acts at the brush border of the small intestine mucosa to inhibit the NPC1L1 transporter and reduce cholesterol absorption from the gut
C.it is a bile-acid binding resin that sequesters bile acid in the intestine and prevents enterohepatic circulation of bile acids which results in lowering of cholesterol
D. It is an HMG-CoA reductase inhibitor which competitively inhibits the enzyme that catalyses the synthesis of cholesterol, thus lowering cholesterol synthesis
E. it is a monoclonal antibody which inhibits the enzyme PCSK9 thus increasing LDL receptor expression on the surface of liver cells, which means more LDL cholesterol is removed from the blood
D. It is an HMG-CoA reductase inhibitor which competitively inhibits the enzyme that catalyses the synthesis of cholesterol, thus lowering cholesterol synthesis
What are baroreceptors?
Mechanoreceptors sensitive to change in rate of pressure change and steady/mean pressure
What are the main baroreceptors in the arterial systemic circulation?
Carotid body baroreceptors + Aortic arch baroreceptors
- Carotid Body Baroreceptors @ Carotid Artery –> CN IX ≈ NTS (MCVC)
- Aortic Baroreceptors @ walls of Aorta –> CN X ≈ NTS (MCVC)
Which of the two main baroreceptors groups is more important and why?
Carotid sinus/body receptors > Aortic arch baroreceptors ≈ respond to pressures ranging from 60-180mmHg cf aortic arch receptors have higher threshold pressure and less sensitive than carotid sinus receptors ≈ small ∆ in arterial pressure ≈ ∆ carotid body baroreceptors > aortic arch baroreceptors
What are the cardiopulmonary baroreceptors?
Cardiopulmonary baroreceptors ≈ low-pressure receptors ≈ sense central blood volume ≈ stretch of vessel walls (compliance means large volume change causes little pressure change due to compliance) ≈ atria, ventricles, veins and pulmonary vessels
What occurs to cardiopulmonary baroreceptors if blood volume is reduced?
Blood volume reduced ≈ reduced blood pressure ≈ cardiopulmonary baroreceptors detect deviation ≈ SNS increase CO (chronotropy, inotropy, dromotropy, lusitropy) + TPR (arteriolar vasoconstriction + venous vasoconstriction) + PSNS decrease inhibition of CO
What is the chief integration centre for blood pressure control?
Medullary Cardiovascular Control Vasomotor Centre (MCVC)
When would the set-point for arterial blood pressure change?
Adaptation in physiology and pathology ≈
- Exercise
- Hypertension
Explain how baroreceptor changes according to an increased arterial blood pressure?
Baroreceptor reflex ≈ Arterial blood pressure ≈ set-point (or cardiopulmonary baroreceptors) ≈ baroreceptors accustomed ≈ firing rate ≈ Sinus nerve of Hering (Glossopharyngeal nerve CNIX) + Aortic nerve (Vagus nerve CNX) ≈ NTS (MCVC) ≈ effect
Increase blood pressure ≈ deviation from set-point ≈ baroreceptors detect increased arterial blood pressure ≈ increased firing rate = increased frequency of impulses ≈ relayed along CNIX and CNX ≈NTS (MCVC) ≈ PSNS (medial portion of MCVC) > SNS (lateral portion of MCVC) i) Reduced SNS tone ≈ reduced NE at ß1, ß2 and a1 ≈ reduced cardiac output (chronotropy, inotropy, lusitropy, dromotropy) + reduce TPR (reduced arterial constriction + reduced venous constriction) ii) Increased PSNS tone ≈ increased ACh at M2r ≈ reduced CO (negative inotropy + negative lusitropy)
Outline the mechanistic physiological changes which occur in response to a decreased blood pressure.
Decrease blood pressure ≈ deviation from set-point ≈ baroreceptors detect decreased blood pressure ≈ reduced firing rate ≈ reduced frequency of impulses ≈ relayed along CNIX and CNX ≈NTS (MCVC) ≈ PSNS (medial portion of MCVC) < SNS (lateral portion of MCVC) ≈
i) Increased SNS tone ≈ increased NE @ ß1r + a1r; ß2r ≈ increased CO (chronotropy, lusitropy, inotropy, dromotropy) + increase TPR (arterial constriction + venous constriction) + increase renin secretion from kidney (renal ß2 receptors)
What does the baroreceptor ultimately do and how?
Baroreceptor maintains constant pressure + preserves flow to brain and heart as vasculature of heart and brain do not participate in baroreceptor reflex-mediated changes ≈no vasoconstrictor effects + perhaps vasodilator effects ≈ not impinged ≈ prevents blood flow falling when pressure falls
What graph would describe the relationship between arterial blood pressure and impulse frequency from carotid sinus?
Graph with Frequency of impulses (Hz) against arterial blood pressure (mmHg) with curve being sigmoidal
- Increase arterial blood pressure ≈ increase sigmoidal curve RHS ≈ increase Hz of impulses from carotid body
- Decrease arterial blood pressure ≈ decrease sigmoidal curve LHS ≈decrease Hz of impulses from carotid body
What is the primary purpose of the baroreceptor reflex?
How can this be shown experimentally?
Reduce minute-to-minute variations or arterial pulse shown experimentally by denervation of baroreceptors ≈ oscillating arterial pressure
What is the equation for CO?
SV x HR
What are the two main effectors in reflex control of blood pressure?
Use the equation for blood pressure to outline this.
Blood Pressure = TPR x CO
1) Heart
- SV
- HR
= CO
2) Peripheral arterioles
- TPR
What is the response to CNS ischaemia?
Blood flow to medullary CVCC reduced ≈ Emergency pressure control system
- Increased TPR
- Increased SNS
- Increased Systemic Arterial Pressure
What are the main determinants as mediators of HR?
SNS + PSNS + Adrenaline
What are the main determinants as mediators of SV?
SNS + EDV + Adrenaline
What are the main determinants as mediators of EDV?
Venous return =
- SNS of veins
- BV
- Respiratory pump
- Skeletal muscle pump
What are the two physiological determinants of TPR?
- Blood viscosity
- Arteriolar radius
What is the long-term regulation of blood pressure?
Control of body fluid volume ≈ blood pressure control via kidneys ≈ renal-body fluid feedback system ≈ arterial pressure increases = urine production increases = diuresis OR arterial pressure decreases ≈ urine production decreases = reduced diuresis
What occurs with regards to EDV and Blood Pressure if you increase extracellular fluid volume e.g. give a patient IV fluids?
Increased ECF volume ≈ increased blood volume ≈ increased mean circulatory filling pressure ≈ increased venous return of blood to the heart ≈ increased cardiac output ≈
- Autoregulation ≈ increased total peripheral resistance ≈increased arterial pressure
- Increased arterial pressure ≈ increased urine output
What is the relationship between arterial pressure and urine output?
Balanced thus increase pressure ≈ urine output increased cf reduced pressure ≈ urine output decreased
What is ADH?
Antidiuretic hormone, arginine vasopressin is a peptide hormone released from the posterior pituitary glad in response to hypovolemia and increased osmotic pressure
List 3 physiological scenarios which lead to an increased secretion of ADH.
Osmotic pressure increased
Hypovolemia
Hypotension
AGT II increased
What is the effect of dehydration regarding ADH?
Dehydration ≈ increased [salt] ≈ ∆ osmolarity ≈ osmoreceptors in Hypothalamus sense ≈ trigger AVP/ADH ≈
1) increase water permeability in renal collecting ducts ≈ blood volume ≈ reduced urine production
2) Vasoconstriction ≈ increase total peripheral resistance
What is the RAAS?
Renin-angiotensin-aldosterone system (RAAS) ≈ blood volume and vascular resistance system influencing CO and arterial pressure
Outline the RAAS system
- Angiotensinogen @ Liver
- Renin @ JGA cells
- Proteolytically cleaves AGTen –> AGT I - ACE @ Pulmonary Endothelial cells
- > Cleaves AGT I to AGT II - AGT II @ numerous sites
- Increase TPR @ Peripheral vessels
- Increased secretion of ADH @ Posterior Pituitary
- Increased aldosterone @ Zona Glomerulosa
- Increased efferent vasoconstriction to maintain GFR @ Efferent arteriole of Glomerulus
What is ANP?
Atrial-natriuretic peptide ≈ AA peptide synthesised and stored in muscle cells ≈ released in response to stretch of atria + helps oppose effects of RAAS
What effect does inspiration have on heart rate?
Increase as MCVC neurones inhibit firing of preganglionic PSNS ≈ reduced ACh ≈ reduced PSNS tone ≈ increase HR
What effect does expiration have on heart rate?
Decrease as MCVC neurones increase firing of preganglionic PSNS ≈ increased ACh ≈ increased PSNS tone ≈ decrease HR
What would transection of the spinal cord cause regarding blood pressure?
Transection of spinal cord ≈∆ thoracolumbar outflow ≈ reduced basal sympathetic tone on heat and vasculature ≈ reduced ACh from preganglionic neurones ≈ NE from postganglionic sympathetic nerves ≈reduced binding of ß1 at nodal cells and ventricular cardiomyocytes + reduced NE at a1 + ß2 (a1 predominates) ≈ tonic firing ≈ spinal shock ≈ blood pressure falls
How does the cold pressor response work?
detected by a delta fibres + c delta fibres ≈ afferent neurone ≈ dorsal horn of spinal cord ≈ ascending afferent neurone ≈ spinothalamic tract ≈ synapse in thalamus ≈ integration ≈ efferent SNS output ≈ increase NE at ß1, a1 and ß2 ≈ increase CO, SVR and mean arterial pressure
How does severe trauma impact blood pressure?
deep pain c delta fibres ≈ afferent neurone ≈ dorsal horn of spinal cord ≈ ascending afferent neurone ≈ spinothalamic tract ≈ synapse in thalamus ≈ integration ≈ reduced SNS > PSNS ≈ PSNS tone dominates ≈ increased ACh at M2r ≈ reduced CO, reduced SVR and reduced blood pressure ≈ hypotensive response
What can an injection of BK, serotonin or PGs can cause?
Bradycardia and hypotension as mimics myocardial ischaemia in the posterior or inferior myocardium
The animal behaviourism of a possum playing dead is an example of what regarding blood pressure?
Emotional stress≈ vasovagal syncope ≈ dramatic drop in chronotropy, cardiac output and SVR
What pressure changes occur in the diving reflex?
Cold water on face + rise in PCO2:O2 (= pH drop) ≈ detected by thermoreceptors ≈ relayed by Trigeminal nerve; detected by chemoreceptors centrally ≈ relayed to CNS ≈ integrated by CNS ≈ efferent SNS drive + PSNS decline ≈ peripheral vasoconstriction + reduced HR ≈ reduced metabolic demand however cerebral + cardiac arteries remain unaffected ≈ prolong survival
What does renal hypoxia result in?
Renal hypoxia +/- reduced Hct ≈ EPO release ≈ bone marrow output increases ≈ erythropoiesis ≈ increase circulating mass of RBCs ≈ increase plasma volume with larger RBC mass
Outline the 3 stages of circulatory shock.
1) Compensated shock (non-progressive): normal CV regulatory mechanisms compensate for initial decrease in CO + arterial pressure ≈ baroreceptor response + hormonal (RAAS + ADH/AVP) ≈ increase HR + SVR ≈ increase CO
E.g. unit of blood
2) Progressive shock: positive-feedback cycle ≈ blood pressure decreases to level below autoregulation of blood flow in heart and brain ≈ organs maintain CV system, (heat and brain) deteriorate due to hypoperfusion.
MOA: Coronary circulation compromised ≈ myocardial contractility reduces ≈ reduced HR + SV ≈ reduced CO; Brain hypoperfusion ≈ deterioration of vasomotor centre in brain ≈ reduce vascular resistance ≈ reduce venous return + SVR ≈ reduce arterial pressure
3) Irreversible shock: Cardiac and cerebral function irreversible ≈ poor tissue oxygen delivery on tissue metabolism ≈depressed mental function; loss of consciousness; renal failure and generalised muscle weakness
How do you calculate MAP?
Pulse Pressure = SBP – DBP
MAP = 1/3 PP + DBP
What is compliance?
Relationship between volume and pressure which is generated by the presence of the volume and property of vessel undergoing deformation
Complicance = ∆V/ ∆P
Describe the difference between a non-compliant and a compliant vessel. Give an example of where you may find each in the body.
Non-Compliant: Rigid tubes resisting expansion when internal pressure rises
- Big change in P with small change in V
- Capillaries + Arterioles
Compliant: Increase in pressure leading to change in vessel wall and change in volume
- Small change in P with large change in V
- Arteries + Veins
Give the Law of LaPlace.
Using this law, explain how an aneurysm occurs.
T = P R
Aneurysm: Weakening wall thus radius increases to reduce the tension as P remains the same, may swell until potential rupture.
Give the Law of LaPlace.
Explain how capillaries function, using this law.
Capillaries: Extremely thin (low R) and withstand pressure. T = PR and radius is low so pressure reduced prior to blood reaching capillaries to reduce tension. This requires less muscular wall.
State 3 factors which cause vasoconstriction, one at each level of control
Sympathetic
Adrenaline
AGT II
AVP
Myogenic response
Endothelin-1
State 3 factors which cause vasodilator, one at each level of control
NO-releasing nerves
Adrenaline
ANP
Hypoxia K+, CO2, H+ Adenosine NO BK
Outline the differences between the 3 types of muscle found in the body.
Skeletal: Long fibres; multinucleate; peripheral nucleus; voluntarily controlled; striated
Cardiac: short fibres; single nucleus; central nucleus; involuntary; striated; lipofuscin granules
Smooth muscle: single nucleus; central nucleus; involuntary; non-striated
Outline the common side effects of statins.
GI disturbances Rash Insomnia Angio-oedema Myositis
Outline the common side effects of Fibrates.
GI disturbances
Myositis
Outline the common side effects of Ezetimibe and colestyramine
GI symptoms
Outline the common side effects of Nicotinic acid.
Flushing Itching Nausea Numbness and tingling Worsens gout Diabetes Angina
State 3 side effects of PCSK9 inhibitors
Nausea Soreness at site Itchiness at site Joint pain Back pain
What should you be aware of when prescribing atorvastatin with antibiotics?
Atorvastatin + Ciclosporin
- Close monitoring
- Avoid concurrent use
- Safety net with myopathy symptoms
- Reduce dose -> 10mg
Atorvastatin + Clarithromycin
- Reduce dose -> 20mg
- Safety net with myopathy symptoms
