Cardiovascular physiology & pharmacology Flashcards
Cardiac AP?
- Phase (0) = Rapid depolarization - opening of fast sodium channels
- Phase (1) = Sodium channels close and potassium channels open
- Phase (2) = Plateau - open L-type calcium channel. Slow repolarization
- Phase (3) = Rapid repolarization - L-type calcium channels close and potassium efllux occurs
- Phase (4) = Sodium / potassium pumps restore the ionic gradients. Slow loss of potassium
Absolute refractory period ?
- Plateau phase / Phase (2)
2. Another AP cannot be generated
Relative refractory period?
Occurs between phases 3 & 4
Pacemaker AP?
- SA nodes have PM potential
- This is dependent on the leakage of sodium into the cell in phase (4)
- Threshold potential is at -40 mV
- Phase (3) = Repolarization. Calcium channels close and potassium channels open with efflux of potassium
- Phase (4) hyperpolarization occurs and potassium efflux stops - Threshoold potential is reached
CVP curve ?
A = Atrial contraction
C = Tricuspid valve elevation into RA
X = Downward movement of contracting RV
V = Back pressure from blood filling the RA
Y = Tricuspid valve open is ventricular diastole
Pathologies of A-wave - CVP?
- Absent in AF
- Large wave if atrium has hypertrophy
- Tricuspid stenosis = Cannon A-waves
Pathologies of V-waves - CVP?
- Giant V-waves are cause by tricuspid incompetence / regurgitation
Factors affecting stroke volume?
- Preload
- Contractility
- Afterload
Preload ?
- Represented by venous return
2. Depends on blood volume, posture and venous tone
Afterload represented by?
- Peripheral vascular resistance
Blood pressure regulation?
- Short-term
2. Long-term
Short-term Blood pressure regulation?
Mediated by;
- Arterial baroreceptors
- Cardiac baroreceptors
- Vasomotor centre in the brainstem
Long-term Blood pressure regulation?
- Neuronal
- Hormonal
- Renin angiotensin aldolsterone system
Frank-starling relationship?
The force of contraction of cardica muscle is proportional to it’s initial fibre length
Increased End Diastolic Volume?
There is increase in stroke volume due to increased forceful contraction
LVEDV may be used as preload
There is increased cardiac output
Not favourable in heart failure
Frank starling curve? Right and downward shift ?
- Heart failure
- Beta-blockers
- Hypoxia
- Acidosis
Frank starling curve? Left and upwards shift ?
- Inotropes
- Sympathetic stimulation
Improvement in contractility
Venous return?
Components include;
VR = MSFP - RAP / Rven x 80
MSFP = Mean systemic filling pressure
RAP = Right atrial pressure
Rven = Venous resistance
Determinants of venous return?
- Presence of pressure gradient along the vessel
Abscence of venous return?
Occurs when RAP = MSFP then no pressure gradient exists and thus VR = 0
This will occur at RAP of 7 mmHg
Flow / venous return increases?
- With reduction in RAP
2. Reduction of resistance in the venous system increases the venous return and cardiac output
Baroreceptors?
- Mechanoreceptors
- Respond to stretch
- Temrinal myelinated nerve endings located within the vessel walls and cardiac chambers
- Their AP / firing rate is altered in response to changes in BP
- Create a negative feedback mechanism
- Located in the carotid sinus and aortic arch wall
Classification of Baroreceptors?
High pressure baroreceptors: Carotid sinus and aortic arch
Low pressure barorreceptors; Chambers of the heart, large systemic veins and pulmonary beds.
Baroreceptor reflex? See picture diagram
- Increased BP
- Baroreceptor discharge impulses in carotid and aortic vessels
- Along vagus and glossopharyngeal nerves to the brainstem
- Discharge along the nerves increases with increase in BP with reduction in sympathetic outflow and increase in parasympathetic flow
- Thus reduction in blood pressure
Immediate response to blood loss?
- Baroreceptor reflex activation
- Reduced parasympathetic activity
- Increased sympathetic activity
- Increase contractility, tachycardia and increased SVR
- Redistribution of CO from the skin, muscle and viscera to the brain and heart
Immediate response to blood loss? Neurohumoral
- Increased ADH secretion from posterior hypophysis
2. Increased adrenal release of NA, A and cortisol via sympathetic nervous system
Aldosterone?
Increases sodium and water at the distal convoluted tubule
Uses of Valsalva maneuver?
- Used to assess autonomic function
2. Termination of SVT
Phases of valsalva maneuver? (4 phases)
- Increased thoracoabdominal pressure. Transient increase of venous return. increased BP and lowering HR
- Sustained rise in thoracic pressure reduces venous return. Fall in BP with restoration by compensatory tachycardia
- Pressure release and further fall in BP. HR remains elevated
- BP is restored with reflex bradycardia
Valsalva maneuver and autonomic dysfunction?
- Persistent fall in BP following +ve intrathoracic pressure
- No relfex tachycardia
- On release of pressure, overshoot of BP does not occur.
Hence impaired baroreceptor reflex
Read haemodynamic changes in ?
- Exercise
- Pregnancy
- Children
- Post-heart transplant
Sympathomimetics - Adrenergic agonists? See picture
- Adrenoreceptors or dopamine receptors
- Basic structure is benzine ring with amine side chains (catechol)
- Naturally occuring or synthetic agents
Adrenaline?
- Dose dependent
- Low doses B1 - Increased CO & coronary dilation. Decrease in peripheral vascular resistance. Splanchnic vasodilation
- High dose Alpha 1 - Rise in SVR
Noradrenaline ?
- Low doses - Tachycardia
2. High doses relfex bradycardia and splanchnic vasoconstriction
Read - Vaughan William classification of antiarrhythmic drugs
See picture
Amiodarone ?
- Poorly absorbed from the gut - Bioavailability 50-70%
- About 95% protein bound
- Large vD 70 L/kg
- Excreted by lacrimal gland, skin and billiary tract
- Weak class I, II and IV action
- Blocks potassium channels and slows repolarization - Increasing duration of AP
- Increases the effective refractory period
- Half-life - 20 to 100 days
- 5mg/kg loading dose and 15mg/kg over 24 hours
Structured responses?
- Indications
- Contraindications
- Side effects
Indications for Amiodarone?
- SVT
2. WPW syndrome
Side effects of Amiodarone?
- Pulmonary fibrosis - After a year of treatment (15%)
- Cirrhosis, hepatitis and jaundice
- Corneal deposits
- Ataxia, dizziness, depression, nightmares
- Thyroid dysfunction - Inhibits convertion of T4 to T3
- Cutaneous hypersensitivity - Blue grey discolouration of skin
Contraindications of Amiodarone ? - Part II exam
- Heart block - Wihtout pacemakers
Digoxin?
- Inhibits Na/K pump
- Increases intracellular sodium and decreased potassium
- Increased influx of calcium in exchange for sodium and thus increased contractility
- increases refractory period of AV node
- Decreases ventricular refractory period
- Acts indirectly by enhancing the release of acetylcholine at the cardiac muscarinic receptors
- Excreted unchanged in urine
- > 2.5mcg/L is toxic
Indications of Digoxin?
- A.fib & A.flutter
2. Heart failure
Side effects of dixogin toxicity?
- Visual disturbance - Orange tone
- GI disturbances
- Downsloping ST depression
Treatment of Digoxin toxicity?
- Correct hypokalaemia
2. Ventricular arrhythmias - Phenytoin & lidocaine
Classification of antihypertensive drugs? - Based on site of action
- Centrally acting - Clonidine, Methyldopa
- Action on heart - Beta-blockers - Atenolol
- Vasodilators - ACE inhibitors, Angiotensin antagonists (losartan), CCB (Nifedipine), Alpha blockers (Prazosin), Nitric oxide formation ( Sodium nitropruside, GTN), Ganglion blockers (Trimethaphan)
- Kidney - Diuretics
Sodium nitroprusside ?
- Unstable in solution and needs protection from light
- Compensatory tachycardia and rebound HTN
- Increased ICP
- Loss of HPV
- Cyanide toxicity when > 8mcg.kg.min
Cyanide toxicity ?
- Each molecule of SNP undergoes non-enzymatic degradation in RBC
- About 5 cyanide ions are produced
- Cyanide ions metabolised to thiocyanate in the liver and excreted in urine
Mx of cyanide toxicity ?
- Chelating agents - Dicobalt edetate
- Sodium thiosulphate - Converts cyanide to thiocyanide
- Sodium nitrite - Converts Hb to methemoglobin which acts as a buffer to the cyanide
- Use of B12
Beta-blockers ?
- Competitive antagonists at beta-adreno receptors
- Reduces cardiac output , lowering BP
- reset baroreceptor activity
- Inhibition of renin-angiotensin system
- Presynaptic inhibition of noradrenaline release
Classification of beta blockers?
See pictures
Indications for use of beta-blockers?
- Chronic HTN
- IHD
- Atenuation of laryngoscopy
- Anxiety
- Thyrotoxicosis
- Pheochromocytoma
Contraindication for beta blockers?
- Cardiac failure
- B1 contraindicated in patients with symptomatic bradycardia
- AV block
- Non-selective used with caution in asthmatic patients
Side-effects of beta blockers?
- Bronchospasm
- Cardiac failure
- Heart block
- Mask signs of hypoglycaemia
- Worsen PVD
- Depression and sleep disturbances
Classification of diuretics ?
- Acetazolamide
- Osmotic diuretics (Mannitol)
- Loop diuretics (Furosemide)
- Thiazide diuretics
- Potassium sparing diuretics
Mannitol?
- Freely filtered at the glomerulus
- Not reabsorbed in the tubules
- Increases the osmolarity of the filtrate
- Urinary volume is increased by osmotic effect
