CVR PHYSIOLOGY YEAR 1 PDF

PHYSIOLOGY  Cardiac Physiology ~ Heart pumps from low pressure veins to high pressure arteries BP in pulmonary circuit is about 28/8 mmHg - - BP in systemic circuit is about 120/80 mmHg - Heart failure in adult...

PHYSIOLOGY  Cardiac Physiology ~ Heart pumps from low pressure veins to high pressure arteries BP in pulmonary circuit is about 28/8 mmHg - - BP in systemic circuit is about 120/80 mmHg - Heart failure in adults is mostly due to the left ventricle unable to perform its function. For example it’s mostly because it cannot fill (diastolic performance) or eject blood (systolic performance) The cardiac cycle is the start of one heartbeat to the - start of the next Conduction in heart - Intercalated discs allow action potentials to pass to adjacent cells S Myocardial cells can randomly depolarize ↑ This random depolarisation creates a pacemaker potential & Fibrous tissue separated atria from ventricle because it lacks gap junctions so it can electrically isolate them Ion Channels There are 2 main forces that drive ions across cell - membranes: Chemical potential: when an ion moves down its - concentration gradient Electrical potential: when an ion moves away from ions or - molecules with the same charge Ionic movements (conductances) across the myocardial & membrane happen in response to the electrochemical potential gradience that is controlled by selective ion permeability. Properties of cardiac ion channels Selective ~ Voltage sensitive gating (only open when a specific range - is acquired) Time dependence (some are fast and slow at closing and & opening) Cardiac Pacemakers 1. The cells of SA node depolarize over time and this causes the resting membrane potential to gradually decrease (pacemaker potential) 2. When the membrane potential exceeds the threshold action potential is triggered (happens every 0.8 seconds) 3. The AV node cells do the same but slower, so the action potential is triggered before the cells depolarize enough to do it by themselves JOIN THE DARKSIDE  Excitation Contraction Coupling - This represents the process where an action potential leads to contraction of cardiac muscle cells. The way this happens is a chemical signal is converted to mechanical energy with the help of contractile proteins. Calcium plays a huge role in this because it moves in and out of the cytosol during each action potential. STEPS 1. Membrane potential of -60 channels open in the SA node 2. Sodium comes in and inside of cell becomes more positive 3. Gated calcium channels open and calcium slowly enters 4. Cell continues depolarizing (pacemaker potential) 5. When threshold is reached another type of calcium channel opens and calcium comes into cell rapidly 6. This causes rapid depolarization (cardiac action potential) Calcium induced calcium release After depolarization 1. Calcium enters the cardiomyocyte by L-type calcium channels 2. It then activates ryanodine receptors on the sarcoplasmic reticulum 3. These receptors senses Intracellular calcium and triggers its release from the sarcoplasmic reticulum to increase the availability in the cell 4. As contraction ends the Intracellular calcium goes back to the SR via SERCA calcium channel Conduction and ECG Action potentials can be detected using electrodes : The trace depends on the direction of travel, if the cell is depolarizing or depolarizing, size of change in potential Electrical Vectors: during an action potential movement of particles generates an electrical vector. The electrical vector represents the average direction of the impulse P Wave Baseline of ECG is the isoelectric line which represents the RMP PR Interval The P wave represents depolarization of atrial muscle wall. Atrial contraction occurs at peak of the wave Used to determine if impulse QRS Complex conduction from atria to ventricles is Represents ventricular depolarization normal Q- initial downward deflection (impulse is travelling from negative to positive) R- initial upward deflection (peak of this is where contraction starts) S- downward deflection and return to baseline JOIN THE DARKSIDE  Cardiac Volumes Frank- Starling Mechanism & End Diastolic Volume (EDV)- volume of blood in the ventricles - Force of contraction= initial fibre length in diastole at the end of diastole (130ml at rest) - That means an increase in blood returning to the heart ↑ End Systolic Volume (ESV)- volume of blood in ventricles at increases EDV that causes extra stretching which finally the end of systole (60ml at rest) leads to an increase in the next contraction & Stroke volume (SV) is the amount of blood ejected from the & When the heart fills with more blood, it stretches, making ventricles in one beat it stronger and more efficient at squeezing blood out. So ↑ SV=EDV-ESV when the heart is stretched it is more responsive to - Cardiac output (mL/min)= stroke volume (mL/beat)x heart calcium and it contracts more powerfully. So the next rate (beats/min) time it’s stretched less calcium is needed to reach half its Regulation of Stroke Volume maximum strength. Preload- the stretch of the heart muscle (the more the heart Note: calcium coming in makes heart contract and leaving & - fills the more the muscle is stretched (venous return is makes it relax increases during activity) Afterload- the pressure against which the heard needs to - pump to release blood (higher the arterial pressure the lower the SV). If artery wall as are stiff then that means less stretch which causes increased pressure (afterload) Contractility- ability of the muscle to produce force (inotropic - and influence of SNS increase contractility) Neural Control of Heart & Chronotrophic effects- effects of ANS on the heart Positive chronotrophic effects 1. Sympathetic nervous system releases norepinephrine 2. Norepinephrine binds to Beta 1 receptors in the hearts SA node 3. Beta 1 activation leads to increase in the Na channels which speeds up the rate of phase 4 depolarization 4. More calcium channels open lowering the amount of depolarization needed to reach threshold for action potentials 5. Since action potentials are fired more rapidly heart rate increases Negative chronotrophic effects 1. Parasympathetic nervous system releases acetylcholine 2. Acetylcholine binds to Muscarinic receptors in SA node 3. This binding slows down rate of action potentials causing slowed heart rate Systolic BP is determined by characteristics of SV being ejected by the heart & and the ability of the aorta to stretch Diastolic BP is determined by the energy that is stored in the elastic fibres that = are stretched during systole Elastic Tissue Elastic tissue is stretched when blood is pushed into the vessels & The elasticity absorbs the pressure preventing sharp rise in pressure & Between heartbeats the elastic tissue recoils putting continuous pressure on the - blood inside the vessels causing continuous blood flow S If elastic recoil wasn’t there the pressure would fall dramatically between breaths (so will blood flow) Windkessels effect- blood flow in aorta is continuous (balloon blowing up and - slowly releasing air) JOIN THE DARKSIDE  BP regulation by autonomic and hormonal mechanisms Baroreceptor reflex - Baroreceptors in carotid arteries and aorta detect pressure, if BP rises they send signals to slow heart rate and lower BP. This reflex adjust BP when posture change or sudden shifts in blood volume (like standing up). If BP stays high for long Baroreceptors may adjust to a new higher “normal”. For longer term BP control, body uses hormones like Renin- angiotensin-aldosterone mechanism Arterioles When they constrict this increases the resistance and ↑ decreases blood flow When they dilate this decreases resistance and increases blood flow 7 Arterial pressure is the product of cardiac output and peripheral resistance BP rises with age & Age Related Changes Increased stiffness of large arteries due to arterisclerotic - lesions and calcification Decreased Baroreceptor sensitivity ↑ Increased responsiveness to SNS activity & Alteration in RAA system relationships & Hypertension & Cardiac output and blood volumes are normal but resistance is increases Secondary hypertension is caused by kidney disease, - anatomic considerations, coarction, narrowing of aorta or chronic changes in vascular structure Effects & - Stroke Damage to eye capillaries - Oedema / Renal failure - Injury to artery wall as - Heart failure JOIN THE DARKSIDE  Artherosclerosis - Caused by injury to epithelium - In response leukocytes are sent to create an inflammatory response. The result is retention and oxidation of lipoproteins. Monocytes turn into macrophages that consume LDL. There is a plaque buildup leading to early sign of artherosclerosis. JOIN THE DARKSIDE  Respiratory Physiology Respiration: exchange of gases between the atmosphere, blood, and cells : 3 processes is required for respiration to occur: Ventilation (breathing), external (pulmonary) respiration, internal (tissue) - respiration At rest normal human breathes 12-15 times a minute Air mixes with gas in the alveoli and by simple diffusion oxygen enters the blood in the capillaries while CO2 enters alveoli The resp system can be divided functionally into the conducting zone and respiratory zone Dead space: the part of your airway that doesn’t participate in gas exchange (the conducting zone). About 150 ml of air. Alveolar dead space: some air reaches the alveoli, but if those alveoli don’t & get enough blood flow, no gas exchange happens. This amount can change depending on your health or in certain diseases. The conducting zone transports air to lungs, warms, humidifies, filters, and & cleans air, and this is where voice production occurs The upper airway has all structures from the nose to the vocal cords - The lower airway has the trachea and the bronchial structures to the alveolus - Breathing through the nose VS mouth - Nose breathing is better because it filters out particles, protects the lungs, and - adds moisture to the air you breathe in. In order to do this it uses its large surface area created by structures inside like the nasal septum and turbinates. Since the nose has more resistance than the mouth during exercise people - tend to switch to mouth breathing for easier airflow. Surface Tension is the force that pulls molecules together at the boundary between air and liquid. This force is increased in the alveoli. Smaller alveoli have more and pressure and are more likely to collapse compared to larger ones. Surfactant produced in the lungs lowers surface tension. Ventilation Air always moves down its concentration gradient (high pressure to low pressure) Boyles Law: if volume of gas increases, its pressure decrease. If volume of gas decreases, pressure increases Example: in the lungs when the chest gets smaller (ribs move down, diaphragm moves up), the space in the chest decreases. This squeezes air in lungs, increasing its pressure. The high pressure pushes the air out of the lungs (exhalation) JOIN THE DARKSIDE - Inspiration is active while expiration is passive ↑ During exercise expiration is active and the abdominal muscles contract I Transpleural pressure: pressure difference between the outside and the inside of the lungs. C The alveoli should remain open to participate in gas exchange. The inflation of one alveoli helps inflate another. Factors that affect gas exchange: Blood gas barrier is 0.2-0.3Um Surface area, diffusion gradient, diffusion distance : Distance of diffusion increases with fluid, · - Fick’s Law explains how gasses move across a membrane, it states normal lungs distant is 0.2-0.4 Um that the rate of gas diffusion depends on: - Surface area: more area=faster diffusion - Thickness of the membrane: thinner membrane=faster diffusion Difference in gas concentration: bigger difference=faster diffusion S Lung compliance affects pulmonary ventilation. It is how easy the ↑ lungs and chest can stretch and expand. It’s measured by how much the lung volume changes when the pressure changes (V/P). If the lungs are stiff like in pulmonary fibrosis it’s harder for them to expand so compliance is reduced Elasticity- the lungs have elastic tissue that stretches when you - breathe in and helps push air out when you breathe out by snapping back into place (recoiling). If a disease like emphysema damages this elastic tissue, the lungs can’t recoil properly. This makes it harder to breathe out. * Due to gravity In external respiration oxygen moves from the air sacs in the lungs to - the blood in the pulmonary capillaries. At the same time CO2 moves from blood to the alveoli to be breathed out. In internal respiration oxygen moves from blood in the body’s - systemic capillaries into the tissues where it’s needed. At the same time, CO2 moves from tissues into the blood to be carried back to the lungs. Perfusion: blood flow reaching alveoli - Ventilation: amount of gas reaching alveoli & - The Ventilation-perfusion ratio (V-Q) shows how well air (ventilation) and blood flow (perfusion) are matched in the lungs Normal ratio is 0.8 (slightly more blood flow than air) In the upright lung: - - Apices (top of lungs)- more air than blood, so V-Q ratio is higher than 0.8 - Bases (bottom of lungs)- more blood than air, so the V-Q ratio is lower than 0.8 JOIN THE DARKSIDE  Factors that decrease V-Q Ratio & Chronic bronchitis, asthma, pulmonary oedema, pulmonary fibrosis Factors that increase V-Q Ratio Increased ventilation or decreased perfusion & & In pulmonary embolism, a blood clot blocks blood flow to part of the lungs. This means the area gets air but no blood so V-Q ratio increases In COPD, damaged alveoli reduce blood flow, even though the lungs are breathing in lots of air. The V-Q ratio is high : Normal automatic process of breathing originates in impulses that come from the brain stem. The cortex can override these centres if voluntary control is needed Eupnea- normal breathing Apnea- no breathing Dyspnea breathing- laboured Tachypnea breathing- rapid Costal breathing movement only- breathing by rib Diaphragmatic breathing movement only- breathing by diaphragmatic Hypercapnia: when CO2 levels in the blood rise slightly, it increases acidity and triggers - sensors in the brain (central chemoreceptors) and neck arteries (peripheral chemoreceptors) to make you breathe faster Hypoxia: when tissues don’t get enough oxygen, it’s usually because there’s low oxygen in the blood. This can happen due to high altitude, blocked airways, or fluid in - lungs. It triggers sensors in the neck arteries to increase breathing. Pulmonary stretch receptors are sensors in the smooth muscles of the airways. They respond to lung stretching when you inhale. As the lungs expand, these - receptors send signals through the vagus nerve to the brain, slowing down the breathing rate. This is called Hering-Breuer inflation reflex. This reflex helps regulate breathing automatically: When the lungs are fully inflated, it tells your body to stop inhaling for a moment & When the lungs deflate, it triggers the next breath to start & Chemoreceptors Peripheral- located in the carotid and aortic bodies, respond to decreased arterial PO2 and increased PCO2 & H+, rapidly responding & & Central- located near ventral surface of medulla, sensitive to PCO2 but not PO2 of blood, respond to change of pH of the ECF when CO2 diffuses out of the cerebral capillaries. Control of Breathing - Pons and medulla generate a normal cyclic pattern of respiration altered by homeostatic and adaptive reflexes & The respiratory neurons can be seen from the dorsal view in the pons and medulla of the brain: - The dorsal respiratory group (DRG) controls breathing Ia and IB are 2 types of neurons in the DRG that help control inhalation. Ia is inhibited by lung stretching and IB is excited - Breathing is controlled by motor neurons that send signals to the muscles responsible for inhalation and - exhalation: Inhalation starts quickly then the signal gradually increases causing the muscles to work more. At the end of inhalation the signal suddenly stops causing the muscles to relax and end inhalation. After that the body switched to exhalation which has 2 phases: one for active exhalation and passive relaxation JOIN THE DARKSIDE  Other Influences - Voluntary control & Other CNS area - Motor cortex (during exercise) Other functions of the lungs Acid base balance - Break down certain substances in the blood like bradykinin which helps control blood - pressure - Convert angiotensin 1 into angiotensin 2 (hormone that geckos regulate BP) ↑ Act as a blood reservoir and contains cells that produce heparin (prevent clots) - Involved in immune Defense JOIN THE DARKSIDE  Physical Activity & The Cardiovascular Respiratory System Key Definitions S Physical Activity: skeletal muscle movement that results in energy expenditure above resting levels. , Exercise: physical activity that is planned (training for a sport) & Sedentary Behaviour: Activities while sitting or lying that have little to no movement and expend less than 1-1.5 METS I VO2max: the maximum rate that the body can take, transport and utilize oxygen (measure of the whole body’s ability to work efficient). Basically how much oxygen the body can use during intense exercise. The higher the VO2max the fitter you are. Metabolic Equivalent (METs): a way to measure the energy the body uses during an activity compared to when resting. Example 1 MET is the S energy the body uses at rest (3.5 ml.kg^-1.min^-1 Exercise Intensity Domains: moderate, heavy, severe, extreme ↑ Steps: 1. Exercise starts 2. Reduction in parasympathetic activity and increase in sympathetic activity 3. Muscles need more O2 4. Signal sent 5. More O2 received Factors Controlling Heart Rate & Ventilation Carotid/central chemoreceptors & Emotional/consciousness factors S Voluntary control T Proprioreceptors - Central radiation & Heart Rate & Ventilation Response to Physical Activity Respiratory Response ↑ Tidal Volume L: amount of air you breathe in or out with each normal breath S Breathing Frequency (beats per minute): the number of breaths you take in one minute. I Minute Ventilation: tidal volume x breathing frequency in L per minute Stroke Volume & Exercise Intensity Increases during exercise (40%-60% of the S VO2max) then levels off Increases in exercise intensity cause increase in systolic & and diastolic remains relatively unchanged JOIN THE DARKSIDE  Cardiopulmonary exercise testing (CPX) & Involves testing the cardiopulmonary unit (diaphragm, heart, lungs, rib cage, corresponding skeletal muscles ↑ Includes: monitoring of respiratory gas exchange, tidal volume & respiratory rate, blood pressure, heart rate, ECG JOIN THE DARKSIDE  Carriage of Blood Gases - Hemoglobin is known as an allosteric protein because the chains shift around to fit the oxygen - Haemoglobin consists of 2 alpha and 2 beta chains each contains a haem-iron complex - Fetal hemoglobin us different Oxyhemoglobin has a different structure compared to deoxyhemoglobin & & Hemoglobin’s ability to bind oxygen depends in the amount of oxygen (partial pressure) In the lungs (alveoli): oxygen levels are high (104mmHg), so hemoglobin grabs almost the oxygen it can (nearly 100% saturated). In the veins (after oxygen delivery): oxygen levels are lower (40mmHg), so hemoglobin lets go of some oxygen (77% saturated). It releases it for the body’s cells to use. Effect of pH on affinity Low pH=low affinity for oxygen (Bohr effect) High pH=high affinity Effect of PCO2 on affinity Low CO2=high affinity for oxygen High CO2= low affinity for oxygen Effect of Temperature on affinity High temp= lower affinity for oxygen Low temp= higher affinity for oxygen Effect of 2,3 BPG on affinity It is a molecule in RBC that helps hemoglobin release oxygen & It is a 3 carbon isomer of glycolytic intermediate & It binds more strongly to hemoglobin when there’s less oxygen, making hemoglobin let go - of oxygen more easily for the body to use In people with chronic anemia, 2,3 BPG levels increase quickly (5 times more in 1-2 S hours) to help deliver more oxygen to tissues CO2 Transport In Blood After dialysis or transfusions, its levels drop because red blood cells are stressed - 1. When the body produces CO2, a little dissolves in the Usually present at 5mmol/l - blood plasma Increased= low affinity & 2. Most CO2 enters red blood cells: some sticks to Decreased=high affinity S hemoglobin kicking off oxygen and most reacts with water Fetal Hb affinity for oxygen to form bicarbonate and hydrogen ions - Made of alpha 2 and gamma 2 3. Bicarbonate exits the red blood cell and to keep the Has a higher affinity than maternal hemoglobin & balance chloride ions move in (chloride shift) - When maternal Hb releases O2 the fetal Hb can take it up In the lungs & It is unaffected by 2,3-BPG 1. O2 enters red blood cells, binds to hemoglobin and kicks Transfer of Oxygen to Tissues off the CO2 that was attached to it S Myoglobin (proteins found in muscles that stores oxygen) holds onto oxygen more tightly 2. bicarbonate returns to the red blood cell, chloride ions than hemoglobin leave (reverse chloride shift) and bicarbonate combines S When oxygen levels in the blood are low (during exercise), myoglobin takes oxygen from with hydrogen ions to form CO2 and water hemoglobin and stores it in muscles 3. CO2 moves into the lungs and gets exhaled & Unlike hemoglobin, myoglobins curve isn’t S shaped because it can only bind one oxygen molecule at a time - Most CO2 exists as bicarbonate JOIN THE DARKSIDE & Hydrogen ion concentration must be kept constant. Changes in pH affect: & The affinity of Hb for oxygen & The rate of enzyme reactions - The ionization states of many substances Importance of Bicarbonate Ion Mechanisms involved in the bicarbonate balance: S Carbon dioxide production from metabolism (Krebs cycle) J & Exhalation of carbon dioxide by the lungs - Hydrogen ion excretion by kidney Bicarbonate reabsorption - Stomach-parietal cells: acid secretion & Pancreas- duct cell: pancreatic juice S Metabolic processes affect bicarbonate concentration - Respiratory processes affect PCO2 & Metabolic Disorders When the body has a metabolic problem affecting the blood pH: - If blood is too acidic (metabolic acidosis): your breathing speeds up to # remove more CO2, this helps lower acidity If blood is too basic (metabolic alkalosis): your breathing slows down to - keep more CO2, this raises acidity Respiratory Disorders When there’s a breathing problem that affects blood pH: & & The kidneys help balance pH, but this takes 6-12 hours to start working - If blood is too acidic (respiratory acidosis): kidneys make more bicarbonate (a base), recycle bicarbonate, and get rid of extra acids to neutralize the acidity JOIN THE DARKSIDE  Lung Function Lung Volumes & Capacities & Minute Respiratory Volume= total amount of new air moved into the respiratory passages EACH MINUTE & It is the TIDAL VOLUME (mls) x RESPIRATORY RATE (L), so minute respiratory volume is in L/min The total volumes in the lungs can be divided into & volumes and capacities Volumes don’t overlap, cannot be further divided, : and when added together equal the total lung capacity. 1. Tidal Volume (VT) 2. Inspiratory Reserve Volume (IRV) 3. Expiratory Reserve Volume (ERV) 4. Residual Volume (RV) Capacities are subdivisions of total volume that are the sum of 2 or more if the 4 basic lung volumes 1. Inspiratory Capacity (IC): VT+IRV 2. Functional Residual Capacity (FRC): ERV + RV 3. Vital Capacity (VC): ERV + IRV + VT 4. Total Lung Capacity (TLC): IRV + ERV + VT+ RV Note: normal volumes are a function of height, sex, age, and to a lesser degree ethnic group Note: lung volumes are recorded by spirometry except for FRC and RV Pulmonary Function Tests Help in diagnosis and management of patients with pulmonary or cardiac disease Good for continuous monitoring Rarely used as a definitive diagnosis Assessing for Lung Function Static lung function tests- Volumes and capacities Screening for obstructive and restrictive diseases ↑ Static lung volumes measure the maximal effort generates at the beginning Evaluating prior to surgery and ends of the maneuver (based on volume not airflow) Evaluating the patients condition when on a Dynamic lung function tests- Volume and Velocities ventilator & These are assessed during forced inspiration or expiration when maximal Documenting the progression of the disease effort is applied (based on time not just volume) Documenting the results & Pulmonary Function Tests & Assessment of airways resistance S Lung volumes (spirometry) ↑ Pulmonary diffusing capacity Feature,Obstructive Disorders,Restrictive Disorders Definition,Difficulty exhaling air due to narrowed or blocked airways.,Difficulty inhaling air due to reduced lung expansion. Problem,Airflow limitation during exhalation (air trapping).,Reduced lung volume and capacity. & Arterial blood gases Key Lung Volumes,- Increased Residual Volume (RV) and Total Lung Capacity (TLC).- Air remains trapped in the lungs.,- Reduced Total Lung Capacity (TLC), Vital Capacity (VC), and Inspiratory Capacity (IC).- Lungs can’t fully expand. Exercise capacity FEV₁/FVC Ratio,Reduced (usually