Heart Beat And ECG Lecture Notes PDF

`Final CR Lecture Notes 4. Heart Beat and ECG Learning Objectives 1. Describe the structural and functional properties of cardiac muscle, and explain how it differs from skeletal muscle. 2. Briefly describe the events of cardiac muscle cell contraction. 3. Describe how the heart beat...

`Final CR Lecture Notes 4. Heart Beat and ECG Learning Objectives 1. Describe the structural and functional properties of cardiac muscle, and explain how it differs from skeletal muscle. 2. Briefly describe the events of cardiac muscle cell contraction. 3. Describe how the heart beat is generated. 4. Name the components of the conduction system of the heart, and trace the conduction pathway. 5. Draw a diagram of a normal electrocardiogram tracing; name the individual waves and intervals, and indicate what each represents. 6. Name some abnormalities that can be detected on an ECG tracing 1. Control of Heart Beat SA Node: group of specialised cells in the wall of the right atrium near the entrance of the SVC. This is the impulse generating tissue (modified cardiac muscle cells). Spread over atria takes 60ms  Receives blood from the right coronary artery. AV Node: Electrical activity starts in the SA node, spreads across the atria to the atrioventricular node.  Here it is delayed to allow ventricles to fill by 60ms (now 120ms in total).  First degree AV block: PR interval is lengthened by 200 milliseconds. Then it travels to the bundle of his, which splits into left and right branches in the interventricular septum. Further divide into purkinje fibres: cause contraction of both ventricles Action Potentials: last about 100 times longer: 200 milliseconds.  In SA Node cells: constant inward sodium influx at rest. Simultaneous potassium current outwards prevent depolarization. However, this outward potassium current decays with time until it reaches the threshold level (near -40mV) and the cell depolarizes.  The heart rate depends on the rate of decay of the outward potassium current. o Parasympathetic (vagal): inhibit closure of potassium channels (muscarinic receptors)  Slows heart rate o Sympathetic: increase closure of potassium channels (beta adrenoceptor).  Speeds up heart rate.  Ventricular muscle: unique shape o Prolonged depolarization: plateau (prolonged entry of calcium): enter through L type. o Longer refractory period: keeps cells synchronous. 2. Electrocardiogram ECG Leads: there are 12 leads that each show a different picture of the heart.  A lead is the voltage recorded by two points.  ECG: mainly generated by start and ending of action potentials. Bipolar Limb Leads (Frontal Plane)  Lead I: Right to left axillae (- to +)  Lead II: Right axilla and leg (- to +) o Standard ECG.  Lead III: records the signal between the left axilla and leg. (- to +) Unipolar Limb Leads (Frontal Plane) Unipolar: amplitude of the signal is calculated between one physical recording point and one virtual reference point (middle of chest).  aVR: right axilla to centre (+ to -)  o Always has a large Q wave and a small/non-exist R wave  aVL: left axilla to centre (+ to -) o Often very small.  aVF: foot (+ to -). Chest Leads: V1 to V6. They are also unipolar leads: virtual reference in the centre of the chest. In order:  V1: FOURTH IC space, right side of the sternum o Mainly negative (large S wave)  V2: FOURTH IC space, left side of sternum  V3: Directly between V2 and V4  V4: FIFTH IC at the midclavicular line.  V5: Level with V4 at the anterior axillary line  V6: level with V5 at the left mid- axillary line. o Mainly positive Transfers from negative V1 to positive V6. These different leads view different regions of the heart. E.g. V3 and V4: anterior aspect. Overview of different leads: IMPORTANT. Lead 2: Standard ECG Contain the PQRST waves.  P wave: atrial depolarization o Should be smooth or round o Positive in leads I, II, III o Notched/peaked P waves in COPD, CHF.  Q wave: negative. Usually small or absent in lead II (if QRS heads upwards).  PQ: atrial contraction  R wave: positive. Usually present in I, II, II.  S wave: negative. Also, present in I, II, II,  QRS: ventricular depolarization.   ST: ventricular contraction (normally flat and curves upward).   T: due to difference in time of repolarisation of ventricles QRS complex: should last 70 mm Hg)  Steep middle part: Hb releases large amounts of oxygen for a small decrease in pO2 (20 – 40 mm Hg). Heat: (due to heavy metabolising): moves curve to the right, unloads more O2 Bohr Shift: heavy metabolising generates more CO2 which is acidic. This moves the curve to the right: unloads more O2. Myoglobin: a form of haemoglobin in muscle. Single subunit: greater affinity for O2 than haemoglobin.  Serves as a buffer store for O2 (binds first to myoglobin before Hb).  Rhabdomyolysis: when myoglobin is released from damaged muscle. May cause renal failure. 5. Haematocrit Haematocrit (percentage of RBCS: usually 45%). indicates how much O2 is carried by the blood.  This is controlled by erythropoietin. Erythrocytes as transport of CO2 √ (IB Review). 12. Microcirculation and Oedema Learning Objectives Draw a labelled diagram showing the anatomy of the microcirculation. Describe the three types of capillaries, continuous, fenestrated and discontinuous, about their structure, distribution and function. Describe how lipid insoluble molecules can move across the capillary endothelium. Draw a labelled diagram showing filtration and reabsorption of fluid along an average capillary. Explain how capillary pressure, plasma colloid osmotic pressure and interstitial colloid osmotic pressure can affect fluid movements between plasma, interstitium and lymph. Know the different causes of oedema and explain the pathophysiology of each. 1. Microcirculation Includes: small arteries, first-order arterioles, terminal arterioles, capillaries and venules.  Metarteriole: directly from terminal arterioles to venules). Anatomy of a capillary bed: Arteriovenous Anastomoses (Metarteriole). 2. Structure of Capillaries Composed of endothelial cells with tight junctions surrounded by basement membrane.  Capillaries contain NO SMOOTH MUSCLE. Continuous Capillaries: Least permeable, most widely distributed capillary.  Sealed endothelium and basal lamina.  Only allow small molecules (H20, ions) to diffuse. Two types: o Numerous transport vesicles: skeletal muscle o Few transport vesicles: located in BBB. Fenestrated Capillaries: Continuous closed basal lamina but epithelium contains small circular pores (60-80nm). This allows for free passage of H20, salts from plasma to tissue. Found in tissues specialized for bulk exchange.  Kidney, pancreases, intestines. Sinusoidal/Discontinuous Capillaries: Highest permeability, have larger fenestrations (of 30-40um) to allow RBCs, WBCs, serum and proteins to pass. Have a discontinuous basal lamina. May have gaps even in between tight junctions.  Liver, spleen, bone marrow. 3. Solute Exchange in Capillaries Diffusion:  Fick’s law (amount moved = area x conc. gradient, diffusion coefficient).  Depends on density of capillaries (high density = high diffusion rate).  Concentration gradient: net rate of diffusion of a substance through any membrane ~ difference between the two sides.  Diffusion coefficient: time it takes for substance to move through material Paracellular Transport:  Substances passed through an intracellular space/cleft.  Often confined to water-soluble substances  Pass through fenestrations (large gap) or calveoli (form vesicles). 4. Fluid Exchange Across Capillaries Determined by hydrostatic and oncotic pressure. Delivers O2, nutrients, etc… Hydrostatic Pressure: favours filtration at the arteriolar end and reabsorption at the venous end of the capillary.  Arterial end = 35 mm Hg  Venous end = 17 mm Hg Oncotic Pressure: large colloid oncotic pressure throughout capillary pulling substances inwards. Net Filtration Pressure: (HPc - HPif) - (OPc - OPif).  Arterial end = 10 mm Hg (water out)  Venous end = - 8 mm Hg (water in). 6. Starling’s Hypothesis Oncotic pressure (plasma proteins): draws fluid into capillary so that with hydrostatic pressure water leaves the capillary at arteriole end and is reabsorbed at the venous end (plasma proteins cannot leave)  Any surplus fluid is deposed in the lympathic system. Fluid loss: 4000 litres of plasma passes through capillaries/day. 0.1-0.2% filtered. 7. Lymphatic System and Oedema Lymphatic System: specialised vessels made up of an endothelium with large intracellular gaps surrounded by permeable b.m.  Contain one-way valves. Water originally from capillaries reabsorbed at the subclavian veins or reabsorbed into circulation at lymph nodes. Approx. 2-4L of lymph is returned to the circulation daily. Failure in correctly distributing it  OEDEMA. Oedema: fluid retention. Too much fluid in tissues.  Systemic: occurs first in lower body (recognised by pitting).  Pulmonary: air spaces in lungs. Causes of Oedema: Increased secretion/filtration of fluid into the interstitium/impaired removal.  Increased capillary hydrostatic pressure (more fluid forced out): heart failure, venous construction  Decreased plasma oncotic pressure (more fluid escapes/less is pulled in). o Kwashiorkor: severe malnutrition. Lack of proteins in blood and tissues causes reduced oncotic pressure so water is not retained by capillaries.  Increased capillary permeability (allows water to flow more freely).  Lymphatic obstruction (inflammation of lymph vessels, obstruction of lymph drainage). Treatment: osmotic diuretics (increase water excretion) or loop diuretics (increase sodium excretion). 13. Pulmonary Circulation Learning Objectives Outline the responses of bronchiolar and arteriolar smooth muscle which maintain a balance between ventilation of the alveoli and blood flow (perfusion) to the alveoli in normal conditions. Define the term ventilation perfusion ratio (Va/Q) and give values for the whole lung, the base and the apex of the lung in a normal subject in the upright position, explaining why these differ. Illustrate, by means of diagrams, how the perfusion of the lung may be considered in terms of different zones. Comment briefly on the effects, on blood passing through the lungs, of a high or a low Va/Q. Briefly explain the changes in circulation at birth (this will be covered again in more detail in the human development course). Two types of circulation in the lung:  Bronchial: supplies the trachea and bronchi. It arises from the aorta, part of the systemic circulation. It makes up about 2% of left ventricular output.  Pulmonary: from the right ventricle, receives 100% of CO. o Takes ~5 seconds for blood to pass through lungs. o Has ~ 280 billion capillaries, 300 million alveoli. 1. Pulmonary Circulation Anatomic Features of Pulmonary Circulation:  Pulmonary arteries are thin walled and have a larger diameter. Less smooth muscle. o Lower pulmonary vascular resistance  Vessels: easily compressed/distended. This allows for a low systolic pressure o Lower pulmonary arterial pressure Mean Pulmonary Arterial Pressure: very low: ~ 15 mmHg. Pulmonary Vascular Resistance: changes in expiration and inspiration:  Inspiration: alveoli expand and compress capillaries that lie beneath them, increasing resistance. However, the extra-alveolar capillaries are slightly pulled apart, decreasing their resistance.  Expiration: EA capillaries are compressed and alveolar capillaries expand. 2. Autonomic Nerve Supply Sympathetic nerve supply to lungs via spinal nerves T2 to T6. Postganglionic fibres from paravertebral sympathetic ganglia merge with vagal fibres  pulmonary plexus.   Little need for neuronal control of blood distribution: little sympathetic vasoconstrictor tone. 3. Zones of the Lung Gravity: when standing up, the pressure at the lung apex is much lower than at the base (higher perfusion at bases). Zone 1: no blood flow in the apices of the upright lung (PA > Pa: alveoli compress capillaries). Healthy lung: there is no zone 1! Zone 2: blood flow is pulsatile: flow occurs during inspiration (Pa < ATM: pulls apart the extra-alveolar capillaries). Zone 3: blood flow is constant: pulmonary arterial pressure and venous pressure are always greater than alveolar pressure (PA). Radioactive xenon: measures distribution of blood flow. 4. Lung Compliance and V/Q Measure of how stretchy/distensible the lungs are.  Compliance = change in volume per unit pressure change (C = dV/dP).  Work of breathing: least when inflation/deflation occurs in region of highest compliance.  Compliance is higher at the base than at the apex: higher ventilation. Ventilation and Perfusion Both ventilation (Va) and blood flow (Q): higher at bases. However, blood flow declines more steeply due to gravity. Ventilation Perfusion Ratio: Va/Q. The ratio is lower at the bottom of the lung (more blood flow than ventilation) and higher at the apex (more ventilation than blood flow). Explained by PaO2 and PaCO2 Apex: high paO2 and low PaCO2: good exchange as nearly all the blood coming through is saturated with O2. Base: low PaO2 and high PaCO2. Due to higher blood flow gas exchange isn’t as good, but there is more of it. Airway obstruction: VQ ratio is lower than normal = 0 if no ventilation. Blood flow obstruction: VQ ratio is higher than normal. If no blood flow: V/Q is infinite. 5. Regulation of Pulmonary Blood Flow Pulmonary hypoxia: causes local vasoconstriction. Blood is diverted away from poor ventilated areas and moved to well-ventilated regions. Adaptive system. 6. Pulmonary Circulation during Exercise Increase in CO: increase in pulmonary blood flow. However, no increase in pulmonary arterial pressure as the pulmonary arterial resistance decreases to increase the flow. Done via:  Reflex Relaxation: if pulmonary vessels are stretched: smooth muscle relaxes: enlarges vessels.  Increased PO2 in alveoli: occurs at the start of exercise and initiates reflex relaxation.  Arterio-venous shunts: open in lungs: allow blood to go directly to pulmonary veins (safety). At Birth: the pulmonary resistance is very high (no oxygen). Most of the blood moves from the right atrium to the left atrium through the foramen ovale and from pulmonary artery into aorta via the ductus arteriosus. 15. Renal Structure and Function I Learning Objectives 1. Outline the general organisation of the kidney, ureter, bladder and urethra. 2. Identify the parts of the nephron and describe the role of each component in the physiologic processes involved in urine production. 3. Describe the vasculature of the kidney, relating its unique features to the physiology of urine production and nourishment of the nephron. 4. Identify the components of the juxtaglomerular apparatus and describe its role in regulation of blood and urine volumes and renal homeostasis. 5. Explain the ‘clearance concept’ and how this is used to measure glomerular filtration rate (GFR). State the properties of suitable marker substances and show how clearance, and hence GFR, are calculated. State normal values for the GFR 1. Glomerulus and Bowman’s Capsule Renal arteries travel into the kidney, split to become interlobar vessels  small arcuate arteries in the cortex.  These arteries: terminate in a glomerulus. Glomerulus: Structure enclosed in a tissue called the bowman’s capsule. First stage of urine formation: plasma filtration, occurs here. Filtration pressure: it has an afferent and efferent arteriole which generate a filtration pressure. Afferent arteriole has a larger diameter, so there is a drop in pressure. This forces fluid through the endothelium into the capsular space = 55 mm Hg. Filtration fraction: ~20% (if more: remaining blood would be too viscous). Capillaries in glomerulus: fenestrated and are covered with a layer of podocytes. If inflamed: proteins can entire urine  proteinuria. Glomerular Filtration Rate 25% of CO (1.2l/min) to kidneys.  GFR: Total amount filtered: 120-125ml/min.  Most of this fluid filtered is reabsorbed, so urine flow is about 1ml/min. Renal Plasma Flow: volume of blood plasma delivered (600 ml/min). 2. Proximal Convoluted Tubule Fluid passes from bowman’s capsule  PCT.   Here, filtered materials (such as water) can be reabsorbed into the peritubular capillaries. Materials can also be secreted by the capillaries into the BC. o Excretion = filtration – reabsorption + secretion. About 2/3 of all water filtered in glomerulus: reabsorbed in proximal tubule.  Basal cells in the tubule contain sodium pumps: move sodium into the IF and then into the peritubular capillary. Glucose, amino acids, ions, vitamins can be co- transported. Osmotic gradient generated by Na+/K+ pumps. Water is reabsorbed via osmosis. 3. Clearance GFR can be measured by clearance. Clearance: volume of plasma cleared of a substance per minute.  If all material is cleared (filtered and secreted), clearance = RPF.  Clearance = urine concentration/plasma concentration x urine flow. Inulin: gold standard for measuring GFR. Completely filtered from plasma/not reabsorbed. However, to measure inulin clearance: infuse inulin over a period of hours to reach steady concentration. Creatinine: clinically, clearance is used to measure GFR. Creatinine: occurs naturally in the body. Freely filtered by glomerulus as well as being actively secreted (this leads to overestimation by 10-20%). Renal Plasma flow: clearance can be sued to measure RPF.  Involves the use of PAH (para-amino-hippuric acid). Infused until steady. 4. GFR Expanded Auto regulated: doesn’t change over wide ranges of blood pressures. As the renal blood flow is constant, and the metabolic rate of the kidney (i.e. its oxygen consumption) is constant, the pO2 in the kidney interstitium is a measure of the oxygen delivery to the kidney and thus oxygen carrying capacity of the blood. Therefore, erythropoietin releasing cells are in the kidney. 16. Renal Structure and Function II Learning Objectives  By means of labelled diagrams show the changes in volume and osmolality of tubular fluid along the length of the nephron, in the presence or absence of anti-diuretic hormone (ADH).  State the source, nature, mechanisms of release of ADH. Describe the stimuli for the release of ADH, explain how ADH controls urine volume and osmolality.  Explain how the thick-walled, ascending limb of the loop of Henle plays a key role (in conjunction with ADH) in the production of either a dilute or concentrated urine to meet the requirements of water balance.  Distinguish between the terms 'water diuresis', 'osmotic diuresis', 'diabetes insipidus' and 'diabetes mellitus'. NOTE: blood plasma has an osmolarity of about 300 mOsm. 1. Broad Control of Blood Volume Loss of blood = venoconstriction. Slight increase in heart rate and rise in PVR but blood pressure remains.  Blood volume control: detects loss and reduces urine flow, increases thirst to compensate for loss.  65% of blood is in the capillaries and veins. This acts as a reservoir in case of haemorrhage. 2. Regulation of Blood Volume Regulated by sensors (neuronal and hormonal) that measure VOLUME Neuronal Volume Sensors: sensory fibres found mostly in RA as well as LA. These act as stretch receptors. As there is more venous return: they become more stretched. Signal blood return to heart/minute.  Information travels via vagus to the NTS to obtain information on volume  hypothalamus.  Previously covered in lecture on neuronal control. Hormonal Volume Sensors: are specialized muscle cells also found in the RA and IVC.  If stretched (increased preload), these cells release atrial natriuretic peptide (ANP). Decreases reabsorption of the distal tubule in the kidney: greater outflow of fluid. o Sensory cells can also release brain-derived natriuretic peptide. 3. Hypothalamus (OSMOLARITY) Attached to the pituitary gland via the pituitary stalk. Is a structure composed of tiny nuclei packed together There are two important nuclei involved in water balance: the supraoptic and paraventricular nuclei.  Contains osmoreceptors: measure osmotic pressure of blood through them.  They send axons down the pituitary stalk to the posterior pituitary. They secrete ADH. ADH: antidiuretic hormone: peptide containing 9 aa. If a high blood solute concentration is detected: ADH is released. Increases sodium reabsorption to retain water. This also induces thirst. 4. The Loop of Henle Urine = x4 concentrated as plasma osmolarity. Made possibly by the loop of Henle, which generates concentrated fluid in the renal medulla (can be as high as 1200 mmol/l). Loop of Henle consists of ascending and descending loop:  Descending Loop: receives fluid from PCT. Has many aquaporins that allow water to leave the tubule and the fluid to become more and more concentrated.  Ascending Loop: active transport of sodium and chloride out of the tubule: keeps ECF of medulla highly concentrated in lower regions while returning it back to normal before it enters the collecting duct. It has a thinner and thicker part. Mechanism of Na+/Cl- Transport Out: occurs mainly in the thicker part of the ascending loop. This thicker part is impermeable to water.  ROMK: potassium transporter (ATP dependent). Transport potassium out into the lumen. This creates a positive voltage (10mV) in the tubular lumen.  Na-K-Cl Cotransporter (NKCC2): allows these ions to move in passively down their concentration gradients into the epithelial cell. The positive potential generated by the ROMK channels enhances this inward transport.  Sodium: actively transporter out of the epithelial cell by the Na+/K+ pump (also provides K+). Chloride moves out passively. Loop Diuretics: e.g. furosemide: block the transport of sodium and chloride out of the loop of Henle by inhibiting NKCC2 channels. 5. Collecting Duct Main action of ADH. Dilute fluid passes from ascending loop  distal tubule  collecting duct. If channels are open: most water is reabsorbed (low to high solute concentration). If closed it is not. Urea: actively pumped out of the collecting ducts into IF. This further increases solute concentration in renal medulla. Countercurrent Multiplier: process of pumping salts into the extracellular fluid around the loop of Henle. Countercurrent Exchange: provided by vasa recta. These prevent the wash out of blood as it follows the tubule in osmolarity. Supplies cells of the loop of Henle with oxygen without interfering. 17. Hormonal Control of Blood Pressure Learning Objectives 1. Describe the renin-angiotensin-angiotensin system and explain its role in blood pressure regulation 2. List common drugs which can be used to control hypertension and explain their mechanism of action Compared to the neuronal system, the hormonal system works on a slower time scale. 1. Juxtaglomerular Apparatus Sensors for blood pressure in distal convoluted tubule. Three components:  Macula Densa Cells: lie in the wall of the distal tubule o Detects sodium concentration. If Na + low = GFR is low. o Tubuloglomerular feedback: attempt to increase the GFR by relaxing the smooth muscle around the afferent arteriole and increasing the filtration pressure.  Mesangial Cells: lie between the afferent and efferent arteriole.  Juxtaglomerular cells: lie around the walls of the arterioles. o Persisting low Na+ concentration = causes the macula densa cells to signal the juxtaglomerular cells. o This release renin into the efferent arteriole. 2. The Renin-Angiotensin-Aldosterone Pathway Renin travels to venous blood, meets angiotensin (secreted by the liver)  Renin enzymically cleaves angiotensinogen  angiotensin I.  Angiotensin I pass in lungs  cleaved by angiotensin-converting enzyme (ACE)  angiotensin II.  Angiotensin II acts on angiotensin II receptors on the lumen of endothelial blood cells. o AT1: stimulate the release of NORADRENALINE. Cause a rise in blood pressure via the sympathetic nervous system as well as direct effect on receptors.  Noradrenaline: causes further release of renin.  Also: found in adrenal cortex. Secrete ALDOSTERONE. o AT2: actions on CNS. Currently undergoing research. NOTE: renin can also be released via sympathetic stimulation (innervates kidney). Aldosterone: acts on receptors on the distal convoluted tubule. Increases reabsorption of sodium. 3. Hypertension Malfunctioning of the Hormonal System If the renal artery of the afferent arterioles is narrowed (atheroma formation), there is reduced blood flow into the kidney = reduces GFR. Leads to more sodium being reabsorbed, excess renin release which will raise blood pressure. Treatment of Hypertension: Control of blood pressure after haemorrhage:  Water moves into blood: keeps volume, osmolarity decreased.  Sympathetic NS constricts veins: reduces venous blood volume.  Renin release: due to dilute blood passing through kidney. 18. Paranasal Sinuses and Larynx (Covered in Anatomy Practical) 19. Introduction to the Respiratory System Learning Objectives 1. List the functions of the respiratory system. 2. Name the main structural features of the lungs. 3. Distinguish between respiratory and non-respiratory components of the lungs and show how histological features. 4. Describe the branching pattern of the respiratory tree, commenting on the significance of the cross- sectional area 5. Outline the causes and social impact (in terms of mortality and morbidity) of an) airways disease; and b) respiratory infection 6. Comment on the major social, environmental and occupational factors associated with pulmonary disease. The respiratory system is not just involved in gaseous exchange but also acid-base balance, phonation, warming, humidification of gas and defense against airborne pathogens. 1. Division of the Airways The components of the respiratory tree are:   Upper Respiratory Tract: oro-pharynx and larynx.  Lower Respiratory Tract: consists of two parts (airways is divided 23 times). o Conducting airways (first 16 divisions up to the terminal bronchioles).  Volume of about 150-200ml (known as dead space: exhaled first) o Gas exchange tissue/respiratory zone (last 7 divisions make: from respiratory bronchioles).  Ends with alveolar sacs (alveolus) = 0.2mm. Around 480 million alveoli.  Rapid increase in total cross-sectional area. This reduces the inward velocity of the air and allows or rapid gas exchange (greater surface area per Fick’s law). 2. Anatomical Features of the Respiratory System Trachae, bronchi, bronchioles: lining is mainly ciliated pseudo-stratified columnar epithelium.  Trachae and bronchi contain cartilage which prevents collapse  These parts also contain smooth muscle: controls the diameter.  They also contain glands (secrete mucus). Respiratory Airways: a very thin epithelium that facilitates gas exchange. NOTE: The epithelium everywhere except in alveoli is covered with a layer of mucus (traps dust/bacteria).  Alveoli therefore has macrophages that are present in high numbers. Mucociliary elevator: mucous moved up towards the throat where it is swallowed.  Epithelium is made up of Type I alveolar cells/pneumocytes (squamous, make up 90% of wall).  As well as Type II alveolar cells/pneumocytes (cuboidal, make up 10% of area). o Produce surfactant: reduces the surface tension and stops alveoli from collapsing.  Made up of phospholipoprotein. 3. Partial Pressures of Respiratory Gases Partial pressure = total pressure in gas mixture x fractional concentration of gas.  Pressure exerted by one of the gases in a mixture of it occupied the same volume as the mixture on its own. PO2 of dry inspired air = 160 mm Hg. In alveolar gas: incorporate water vapor. This reduces the partial pressure of other gases which changes total pressure in the gas mixture.  So, the partial pressure of oxygen will be = 150 mm Hg. PO2 in alveoli = 100 mm Hg PCO2 in alveoli = 40 mm Hg. These pressures vary however between systemic and pulmonary circulation. PO2 is highest leaving the lungs, PCO2 is highest entering lungs. Altitude: oxygen fraction stays constant, total pressure decreases, so PO2 decreases. 20. Gas Exchange and Lung Testing Function Learning Objectives Describe the physical and partial pressures inside the lungs during normal breathing Understand the role and functions of surfactant in the lung Describe the factors that limit gas transfer in the lung Describe the tests used to assess lung function 1. The Fick Principle To maximize gas transport in lungs we have:  Large exchange area  A thin diffusion membrane  A low partial pressure difference  A high permeability coefficient. o How easily the substances dissolve in the membranes. 2. Partial Pressures Average partial pressure of O2 in alveolar gas is = 100 mm Hg.  Due to the ventilation perfusion mismatch (higher ventilation than perfusion in apices): gas in the alveoli in lung apices have a higher partial pressure: closer to tracheal levels of 150 mm Hg. o Apical alveolar gas = 135 mm Hg.  Gas in the lung bases has a much lower partial pressure. o Basal alveolar gas = 92 mm Hg. So, in general, because blood leaving the apices is fully saturated and blood leaving the bases is not (though there is more of it) the blood in the apices will have a higher partial pressure. Difference in Partial Pressures: normally, oxygen transfer is very efficient between alveoli/blood.  O2 dissolves easily in the alveolar membrane and binds to hemoglobin.  Oxygen in alveolar gas = 100 mm Hg, oxygen is mixed pulmonary venous blood = 95 mm Hg. o The difference between this is only 5 mm Hg which makes for easy transfer. Acid-Base Regulation: O2 saturation is not affected by changing breathing rate due to high PO2.  However, CO2 transport is less efficient: PCO2 in alveoli = 40 mm hg, in pulmonary venous blood = 46. o Changing the breathing rate will affect the excretion: keeps blood pH at desired level. 3. Thoracic Wall and Lungs Two important forces hold the thoracic wall and the lungs in close opposition.  Intrapleural Fluid: water molecules in Intrapleural fluid are attracted to each other and resist being pulled apart. Therefore, the pleural membranes tend to stick together.  Negative Intrapleural Pressure: pressure gradient created by the sub-atmospheric pressure between the lung surface and the inner chest wall of the thorax (two pleura). o Around ~4mm Hg less than ATM even if breathing with open glottis (lungs = ATM).  IP decreases in inspiration, increases in expiration. The pleura are two layers of serous membrane:  A parietal layer which covers the lungs  Visceral layer which covers the inner thoracic wall. Boyle’s Law: if the volume of a gas is made to increase the pressure exerted by the gas decreases (decrease in pressure, air sucked in). 4. Inspiration and Expiration Inspiration: the increase in the size of the lungs: intra-alveolar pressure falls sucking air in.  Decrease in pressure is small: only by about 1 mm Hg. Air is sucked in. Expiration: a passive process that usually involves no muscle (elastic recoil of inspiratory muscles).  Recoil makes pressure rise: again, only by about 1 mm Hg above ATM. Air is moves out. Caused by: o Elastic connective tissue o Alveolar surface tension: attraction between water molecules at water- air interface.  Produces a force that would make the alveoli collapse if not lined by surfactant.  NOTE: per Laplace’s law, the smaller the alveoli, the higher the tendency to collapse  P (inward collapsing pressure) = 2T (surface tension) / r (radius). Surfactant: mixture of lipid and protein secreted by T2 pneumocytes. Four different lipoproteins:  B + C (classic type): reduces surface tension.  A + D: coats bacteria and viruses, helps the immune system. (In newborns: fetal lungs cannot synthesize surfactant up to week 28).  Premature babies can have infant respiratory distress syndrome. 5. Lung Function Testing Spirometry: assess prognosis of respiratory disease, assess severity, effect of treatment etc… Measurement of total lung capacity (TLC): measured by inspiration of a fixed volume of gas (helium). Peak flow measurement: assesses airway resistance. Useful in patients with asthma/COPD.  Full inspiration  short sharp blow. Average of three attempts is taken. Test of Ventilation/Perfusion: analyse with isotope scanning.  Reduced ventilation/perfusion causes hypoxaemia (low O2 in blood). Measurement of gas transfer: efficiency of O2 transport across alveolar membrane  Takes measurement of alveolar oxygen partial pressure (oxygen meter).  Compares it to measurement of arterial oxygen partial pressure (pulse oximeter). 21. Pharmacological Treatment of CV Disease Learning Objectives 1. Describe the role of the vascular endothelium. 2. Briefly describe how drugs may be used for treatment of hypertension and angina. 3. Define heart failure and describe its treatment. 4. Describe the renin-angiotensin-aldosterone system and explain its role in blood pressure regulation 1. Hypertension Defined as having a blood pressure of 140/90 or higher.  Most types of hypertension: asymptomatic, with causes often not being known (idiopathic).  May be secondary to another condition (kidney diseases, excessive sympathetic drive etc…) Stage 2: clinical pressure is 160/100 mm Hg or higher Severe: clinical pressure is 180/110 mm Hg or higher. Treatment: involves adapting environment/lifestyle and the administering of pharmacotherapy.  Angiotensin Converting Enzyme Inhibitors (ACE): interrupt the renin- angiotensin system. o Ramipril, enalapril (the PRILS). Side effects may be K+ retention, cough.  Calcium Channel Blockers: block Ca entry to vascular smooth muscle, myocardial cells. o Amlodipine. Side effects: flushing, headache, oedema.  Diuretics: decrease intra-vascular volume and therefore CO.  Other Options: include some of the following: o Alpha adrenergic blockers (prazosin) o Aldosterone blockers o Beta blockers (used in heart failure, MIs). Treatment Ladder: A: given if aged under 55 years C: given if aged over 55 years. A+ C: A combination is given in Step 2, A+C+ D: Thiazide-like diuretic is added in Step 3. 2. Heart Failure An increased venous return usually leads to stronger contractions of the heart (Starling’s law). This adaptation fails in heart failure (may be due to ischemic heart disease/valve defects etc…).  Heart failure can be worsened by compensatory mechanisms. Treatment: modify physiological compensatory mechanisms that worsen it if primary cause not corrected:  Aims to improve stroke volume  Reduce pre-load as well as after-load  Improve tissue perfusion/oxygenation. Treatment again involves making adaptations to lifestyle (control fluid intake, minimize salt intake). Drugs:  Diuretics  ACEs (corrects the renin-angiotensin system)  Positive ionotropes (e.g. digoxin). o Digoxin: selectively binds to and inhibits myocyte Na pump (Na/K ATPase). This causes an increase in calcium which causes improvised contractility.  Direct action on conduction at AV (decreases automaticity).  Has a narrow therapeutic effect. 3. Angina Pain arising from ischemic heart disease of myocardial muscle (due to plaque formation).  In other works, the myocardial muscles demand for oxygen exceeds the supply Treatment: works to increase the supply or reduce the demand.  Nitrates: e.g. glyceryl trinitrate (short-acting). It has a dilatory effect on vessels (including coronary vessels, reduces preload. Side effects: head ache, drop in blood pressure.  Beta Adrenoceptor Antagonists: reduces work of myocardium and hence oxygen demand.  Calcium Channel Blockers 4. High Cholesterol Excess of some lipoproteins (LDL) associated with CVS disease. It has multiple causes. Treatment: involves and adaption to the diet as well as administering of drugs.   Statins: one of the most prescribed drugs in the UK. o Inhibits HMG Co-A.  Ezetimibe: blocks cholesterol absorption from the small intestine.  PCSK9 Inhibitors: monoclonal antibodies. Target and inactivate PCSK9 in the liver. o Causes reduced levels of LDL. 22. Structure and Function of Blood Learning Objectives 1. What is blood made of? 2. What is plasma? 3. What are the blood cells? 4. How are they produced? 5. What is anaemia? 6. How do we detect haematological problems? 1. Plasma Forms 20% of extracellular fluid. Consists of:  Water (90%): acts as a solvent, lubricant, cushion (buffer), heat dissipater.  Glucose/Salts/Other Dissolved Chemicals (2%)  Proteins (8%): o Albumin (60%) o Globulin (36%) o Fibrinogen (4%). Plasma Ions: inorganic ions (potassium, sodium, calcium, chloride, bicarbonate, phosphate). These ions need to be balanced to maintain blood pressure and fuel muscle, heart contractions. Plasma Proteins and Carriers: plasma is involved directly in producing an immune response.  Complement proteins: permeability, chemotaxis, enhance ability of antibodies.  Cytokines: released from lymphocytes.  Antibodies: protect against infection. Various other roles: blood clotting, waste disposal, hormones, drugs, osmotic effects etc… 2. Production of Blood Cells Known as the process of hematopoiesis Bone marrow. Bone marrow stem cells (hematopoietic cells): undergo differentiation into myeloid stem cells:  Erythrocyte  Megakaryocyte: platelets  Myeloblast: eosinophil, basophil, neutrophil. 3. Anaemia Always an underlying cause: one of the most common blood disorders (25% of people). Defined as: 