PHYSIOLOGY.docx

Physiology Revision Normal body PH is 7.35 - 7.45 Scenario: Shortness of Breath External respiration is the exchange of gases between the external atmosphere and the lungs: Ventilation Gas exchange between alveoli and blood Gas transport in blood Gas Exchange at tissue level Rate and depth of breath...

Physiology Revision Normal body PH is 7.35 - 7.45 Scenario: Shortness of Breath External respiration is the exchange of gases between the external atmosphere and the lungs: Ventilation Gas exchange between alveoli and blood Gas transport in blood Gas Exchange at tissue level Rate and depth of breathing is controlled by the respiratory control centre (efferent signals sent from the respiratory centres to the respiratory muscles) Respiratory centres are influenced by chemoreceptors: Central chemoreceptors Most potent stimulator of respiration in normal people - H+ drive (arterial PCO2) Important during lactic acidosis, diabetic ketoacidosis causing hyperventilation to eliminate excess CO2 thus achieving acid base balance Near surface of the medulla Respond to H+ of CSF (CSF separated from blood by BBB, impermeable to H+ but CO2 diffuses easily [CO2 + H2O <-> H2CO3 <-> H+ + HCO3-] & CSF has less protein than blood hence is less easily buffered than blood) Peripheral chemoreceptors - carotid and aortic bodies sense tension of O2, CO2 and H+ in blood May respond to hypoxia, hypercapnia, acidosis, central arousal - anxiety, temp, pain, drugs Responsible for hypoxic drive of respiration (secondary stimulator of respiration in normal people i.e. not important in normal respiration but may become important in those with chronic CO2 retention like COPD patients / at high altitudes) Higher brain centres Stretch receptors on walls of the bronchi (Hering Breuer Reflex to guard against hyperinflation) Juxtapulmonary J receptors stimulated by capillary congestion / pulmonary oedema / pulmonary emboli causing rapid, shallow breathing Joint receptors stimulated by joint movement Baroreceptors cause an increased ventilatory rate in response to a decreased BP Respiratory rhythm is generated by the medulla // Respiration modified by input from pons The ventilatory pump is important in maintaining normal respiration. It consists of: The respiratory muscles (can be affected by neuromuscular weakness) Inspiration is an active process that depends on muscle contraction - major inspiratory muscles are diaphragm and external intercostal // accessory muscles of inspiration such as SCM, scalenus, pectoral contracts only during forceful inspiration Diaphragm (phrenic N. C3,4,5) contracts and flattens thus increasing volume of thorax vertically External intercostal muscle contraction lifts ribs and sternum outwards in a bucket handle movement Expiration is usually a passive process (dynamic airway compression due to rising intrapleural pressure), only during active expiration do abdominal and internal intercostal muscles contract The peripheral nerves that transmit signals from the respiratory controller to the respiratory muscles The chest wall (can be affected by decreased compliance - kyphoscoliosis) The pleura provides transmural pressure (intrathoracic - intra alveolar) gradient for the lung to expand (can be affected by loss of transmural pressure gradient - pneumothorax = hyperresonance, decreased breath sounds). Other pressures in the lungs (Boyle’s Law): Atmospheric pressure (is 760mmHg, can assume 0) Intrapleural / Intrathoracic pressure (< atmospheric pressure) - therefore, always negative and falls during inspiration, rises during expiration Intra Alveolar pressure (= to atmospheric pressure) - negative during inspiration and positive during expiration The airways that connect alveoli to atmosphere (can be affected by increased airway resistance as in asthma / COPD) Factors that keep the alveoli open are the transmural pressure gradient / pulmonary surfactant / alveolar interdependence Factors promoting alveolar collapse are elasticity of stretched pulmonary connective tissue / alveolar surface tension balanced via surfactant premature babies might not have enough surfactant hence can struggle to breath - respiratory distress syndrome of the newborn due to the inability to overcome high surface tension of alveoli Airway resistance Flow = Pressure / Resistance Usually resistance to flow in the airway is normally low (depends on the radius of the airway), thus air moves with a small pressure gradient Parasympathetic stimulation causes bronchoconstriction // Sympathetic stimulation causes bronchodilation Dynamic Airway Compression Intrapleural pressures are usually negative Intrapleural pressures fall during inspiration and rise during expiration Rising intrapleural pressure pushes against alveoli and compresses it, thus pushing air upwards In normal people, this process occurs easily In those with airway obstruction, likelihood of collapse is more (worse if patients have decreased elastic recoil) Compliance Measure of effort needed to stretch/ distend the lungs Volume change per unit of pressure change across lungs The less compliant the lungs are, the more work required to achieve a given degree of inflation Compliance is decreased in pathology like pulmonary fibrosis = causing restrictive pulmonary disease (more work of breathing needed) Therefore, work of breathing is increased when: Need for ventilation ↑ Airway resistance ↑ Chest expansion ↓ Elastic recoil ↓ Compliance ↓ on the other hand if compliance increases, it is harder to get air out of the lungs such as in emphysema + dynamic airway compression will also be aggravated = hyperinflation of lungs ; compliance increases with increasing age. The gas exchanger in the lungs comprise of: Alveoli - thin walled inflatable sacs that have single layer of flattened simple squamous type I alveolar cells, thus large surface area Pulmonary capillaries - encircling each alveolus Interstitial space - narrow The factors influencing gas exchange across the membranes: Dalton’s law: Partial pressure gradient (↑ = ↑ exchange) - gas moves from higher to lower Surface area (↑ = ↑ exchange) decreased by emphysema, lung collapse, increased w exercise Diffusion coefficient i.e. membrane solubility (↑ = ↑ exchange) more for CO2 than O2 Fick’s law of diffusion: Thickness (↑ = ↓ exchange) increased by pulmonary fibrosis, pneumonia and pul edema Even though partial pressure gradient for O2 is higher than CO2 (meaning O2 diffuses across membranes easier), this is offset by the diffusion coefficient being higher for CO2 than for O2. Perfusion (↑ = ↑ exchange) decreased by pulmonary embolism Pulmonary ventilation = Tidal Volume x Respiratory Rate = 6L/min Alveolar ventilation = Tidal volume - anatomical dead space x Respiratory rate 4.2L/min Ventilation Perfusion Ratio At the top of the lung, blood flow is least but ventilation is most hence VQ ratio is = infinity THEREFORE, accumulation of O2 in alveoli causes pulmonary vasodilation thus Ventilation Perfusion Matching occurs At bottom, blood flow is most but ventilation is least hence VQ ratio is almost 0 THEREFORE, accumulation of CO2 in blood causes pulmonary constriction thus Ventilation Perfusion Matching occurs Cardiac output can also affect respiration CO = SV * HR SV = EDV - ESV Stroke volume changed depending on diastolic length of myocardial fibres EDV determined by venous return to heart Frank Starling’s Law states that the more the EDV, the higher the amount of blood ejected will be hence the greater the SV will get (but only up to a certain limit!) Heart failure shifts this curve to the right. Heart failure is a syndrome that can result from structural or functional cardiac disorders that impair the pumping ability of the heart. LHF is caused by pulmonary capillary congestion / pulmonary oedema (J receptors stimulated + impaired gas exchange + decreased lung compliance). Controlled intrinsically by the heart muscle itself or extrinsically via nervous and hormonal control Oxygen Binding to Haemoglobin Each haem group can reversibly bind to one O2 molecule. PO2 is the primary factor which determines the percent saturation of haemoglobin with O2 (sigmoid curve - O2 binding demonstrates cooperativity ; flat upper part means that slight drop in alveolar O2 will not affect O2 loading but steep drop in lower part means that the peripheral tissues get a lot of O2 for a small drop in capillary PO2.) Bohr effect: A shift of the curve to the right allows increased release of O2 to tissues in conditions like: Raised temperature Decreased pH (exercise and lactic acidosis) Raised 2,3 BPG Raised PCO2 Foetal haemoglobin has a higher affinity for O2 than adult HbA, hence the oxygen dissociation curve is shifted to the left allowing mother to foetus transfer of O2 even if PO2 is low. Myoglobin - no sigmoid dissociation curve, instead, it is hyperbolic. At large amounts, indicated muscle damage. ANAEMIA IS NOT USUALLY A CAUSE FOR SHORTNESS OF BREATH BECAUSE TEMPORARY INCREASE IN CARDIAC OUTPUT ACTS A COMPENSATORY MECHANISM, THUS ARTERIAL PO2 SENSED BY CHEMORECEPTORS IS NORMAL Description Average Value Tidal volume (TV) Volume of air entering or leaving lungs during a single breath 500 ml Inspiratory reserve volume (IRV) Extra volume of air that can be maximally inspired over and above the typical resting tidal volume 3000 ml Inspiratory capacity (IC) Maximum volume of air that can be inspired at the end of a normal quiet expiration (IC =IRV + TV) 3500 ml Expiratory reserve volume (ERV) Extra volume of air that can be actively expired by maximal contraction beyond the normal volume of air after a resting tidal volume 1000 ml Residual volume (RV) Minimum volume of air remaining in the lungs even after a maximal expiration 1200 ml Description Average Value Functional residual capacity (FRC) Volume of air in lungs at end of normal passive expiration (FRC = ERV + RV) 2200 ml Vital capacity (VC) Maximum volume of air that can be moved out during a single breath following a maximal inspiration (VC = IRV + TV + ERV) 4500 ml Total lung capacity (TLC) Maximum volume of air that the lungs can hold (TLC = VC + RV) 5700 ml Forced expiratory volume in one second (FEV1): Dynamic volume Volume of air that can be expired during the first second of expiration in an FVC (Forced Vital Capacity) determination FEV1% = FEV1/FVC ratio Normal >75% Spirometry for dynamic lung volumes: FVC = Forced vital capacity: maximum volume that can be expelled from the lungs following maximum inspiration FEV 1 = Forced expiratory volume in 1 second FEV1 / FVC ratio = >75% (decreases in obstructive disease like asthma and COPD, normal or increased in restrictive disease) Management of SOB: Correctly position patient O2 therapy Bronchodilators (B2 agonists and anticholinergics) for those with obstructive lung disease like asthma / COPD Patients with pulmonary oedema usually benefit from diuretics Treat the underlying cause of SOB Lifestyle modifications / palliative care FORCE GENERATION BY THE HEART The cardiac muscle is striated due to regular arrangement of contractile proteins The cardiac myocytes are electrically coupled by gap junctions These are protein channels which form low resistance communication pathways between neighbouring myocytes, thus ensuring all electric excitation reaches all cardiac myocytes (i.e. functioning as a functional syncytium) Desmosomes within intercalated discs provide mechanical adhesion between adjacent cardiac cells to allow transmission of tension Muscles: Myofibrils: contractile unit of muscles Myofibrils contain thin filaments actin and thick filaments myosin arranged into sarcomeres. Muscle tensions is produced by sliding of actin filaments on myosin filaments = muscle shortens and produces force This sliding is dependent on ATP interaction between thick and thin filaments ; Ca2+ is important Conduction in cardiac myocytes Cardiac myocytes have excitability. This is the ability of the muscle to respond with stimuli by producing action potentials. Intracellular Na+ levels are low. When an action potential is stimulated, Na+ channels open and Na+ rushes in. Phase 0, depolarization, cell becomes positive. Then, Na+ channel closes and the influx stops (at threshold potential). Then, long acting type Ca2+ channels open, Ca2+ influx occurs. Phase 1, early repolarization. At the same time, K+ channels open and K+ efflux occurs. When Ca2+ influx = K+ efflux, Phase 2, plateau phase. Then, Ca2+ channel closes, K+ efflux continues. Phase 3, repolarisation Phase 4 is resting phase During the absolute refractory period, no action potential can be generated. Through this mechanism, heart spasm is prevented. During the relative refractory period, a high amount of energy can generate an action potential. Excitation Contraction Coupling The opening of long acting type Ca2+ channels in Phase 2 of the action potential allows the influx of Ca2+ from ECF. Action potential duration = 150ms. This in turn stimulates the ryanodine receptors in the terminal cisterns of diads of sarcoplasmic reticulum, thus stimulating the release of Ca2+ from sarcoplasmic reticulum. Then there is diffusion of Ca2+ to myofilaments, where they bind to troponin C to expose cross bridge binding site and thus allow actin myosin binding and trigger sliding, thus contraction. Then, the released Ca2+ is pumped back into sarcoplasmic reticulum or effluxed from the cell membrane via Ca2+ ATPase or via Ca2+Na+ exchanger. Relaxation of myocytes ensues. Cardiac Output and Stroke Volume CO = SV * HR SV = EDV - ESV Regulated by intrinsic (within the heart muscle) and extrinsic (nervous + hormonal control) mechanisms INTRINSIC CONTROL Stroke volume changed depending on diastolic length of myocardial fibres EDV determined by venous return to heart and stretch increases affinity of troponin for Ca2+ meaning the more stretched the heart is due to preload, the more likely it is to contract (unlike skeletal muscle where maximum affinity of troponin to Ca2+ is at rest) Frank Starling’s Law states that the more the EDV, the higher the amount of blood ejected will be hence the greater the SV will get (but only up to a certain limit!) Hence, initially it compensates for increasing afterload caused by HTN (since increased afterload means ESV rises, which contributes to EDV) Heart failure shifts this curve to the right. Heart failure is a syndrome that can result from structural or functional cardiac disorders that impair the pumping ability of the heart. LHF is caused by pulmonary capillary congestion / pulmonary oedema (J receptors stimulated + impaired gas exchange + decreased lung compliance). EXTRINSIC CONTROL This involves nerves and hormones Ventricular muscle is supplied by sympathetic nerve fibres, thus neurotransmitter is Noradrenaline Stimulation of sympathetic nerves increases the force of contraction = +ve inotropic effect Stimulation of sympathetic nerves to the heart also causes a positive chronotropic effect (HR) But too fast a HR can also cause too short systole and diastole Vagal stimulation has an impact on rate rather than contractility A and NA released from adrenal medulla have an inotropic and chronotropic effect CARDIAC ARRHYTHMIAS Atrial Fibrillation Most common arrhythmia - may be symptomatic (palpitations, chest pain, dyspnoea, sweaty, fatigue, syncope) / asymptomatic Chaotic and disorganised atrial activity resulting in an irregular heartbeat // Ectopic foci in the muscle sleeves of the ostia of pulmonary veins ECG: P wave absent Abnormal F wave present Irregularly irregular rhythm ***Therefore may coincide with period of fast VR, hence pacemaker may be required ***Ventricular rates <60 bpm suggest AV conduction disease thus caution with anti arrhythmic drugs and rate controlling drugs + may require permanent pacing! Atrial rate >300 bpm QRS and conduction normal Patterns: Paroxysmal - recurrent, lasting <48 hours, then spontaneously convert to normal sinus rhythm Persistent - lasting greater than 48 hours but can still be converted to normal sinus rhythm Permanent - Inability to convert to normal sinus rhythm Atrial fibrillation: decreased filling times so reduced CO ; can result in CHF with diastolic dysfunction Mx: Spontaneous reversion to sinus rhythm Pharmacologic cardioversion with antiarrhythmic drugs (30% effective) Electrical cardioversion by direct current (90% effective) - sedation / GA needed Management may either be: Rhythm control: to restore Sinus rhythm Pharmacologic conversion with Amiodarone / Direct Current Cardioversion (DCCV) and then maintain Sinus rhythm with antiarrhythmic drugs, catheter radiofrequency ablation (of AF focus in pul veins) or Maze surgery Rate control: to accept AF but control ventricular rate Digoxin / B blockers / Verapamil / Diltiazem / Radiofrequency ablation (of AVN to stop fast conduction to ventricles) ANTICOAGULATION ESSENTIAL DUE TO RISK OF THROMBOEMBOLISM AF carries a risk of thromboembolic stroke especially in the presence of thyrotoxicosis / hypertrophic cardiomyopathy / mitral stenosis / CHA2DS2VASc score (>2) Stroke prevention is done with oral anticoagulation long term (Warfarin for those with valvular disease) C - CHF / LV dysfunction (1) H - HTN (1) A - Age >75 years (2) D - DM (1) S - Stroke (2) V - Vascular diseases (1) A - Age: 65 - 74 years (1) S - Sex: female (1) Prevalence and incidence increases with age Cause associated with: Hypertension, CHF, Sick sinus syndrome, obesity, thyroid disease, familial, cardiac valve disease, septicemia, pericarditis, tumours, alcohol abuse, congenital diseases, cardiac surgery, COPD, Pneumonia, septicemia, vagal cause in athletes May be idiopathic / Genetic especially in young onset (Brugada , Long QT) Antiarrhythmic Drugs that can be used: CLASS 1: Reducing Na+ channel current Lignocaine, Quinidine, Flecainide, Propafenone CLASS 2: B adrenergic antagonists Propranolol CLASS 3: Action potential prolongation Sotalol, Amiodarone, Dronedarone CLASS 4: Ca2+ channel antagonists Verapamil Atrial Flutter Atrial flutter is due to macro reentrant circuit confined to the right atrium Rapid and regular form of atrial tachycardia Episodes can be paroxysmal / persistent i.e. can last from seconds to years Chronic atrial flutter usually progresses to atrial fibrillation, thus carrying the risk of thromboembolic stroke ECG: F wave in sawtooth pattern Atrial tachycardia + / - ventricular tachycardia too Regular rhythm but may be variable Mx: To terminate flutter and prevent a recurrence To control the ventricular response during the arrhythmia RF ablation (long term success rate high) Pharmacologic treatment to slow ventricular rate, restore and maintain sinus rhythm Cardioversion Oral anticoagulation for thromboembolism risk reduction