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)
