Lobcast 4 - Jane Salter

The interview for week four PBL and Sally Thompson learning objectives, the first number of lobs up to log five were to want to do with anatomy for this week. So number one is to revise the anatomy of the trachea bronchial tree and bronchial pulmonary segments. So the trachea is a fibrocardalaginous tube, it's about 10 to 12 centimeters long, about 2 centimeters wide. It starts at mc6, so continues with the larynx just below the crycord cartilage, at the end of the carina, which is t4, t5 level, or at the sternal angle, where it bifurcates into the right and left, me and bronchial. The trachea is made of c-shaped rings of high-align cartilage joined by fibroelastic tissue, and the posterior wall is known as the tracheaus muscle. The trachea is lined by ciliated respiratory epithelium with goblet cells, which secrete mucus. Positioned anterior to the trachea is the thyroid esmus, the archer de aorta, the brachiosyphalic trunk, and the left brachiosyphalic vein. Positioned posteriorly to the trachea is the esophagus, and laterally you will find the lobes of the thyroid and caradid arteries and the recurrent laryngeal nerves. The trachea is supplied by the inferior thyroid arteries, that's the upper trachea, and then the bronchial arteries for the lower trachea, and the nerve supply is through the vagus and the recurrent laryngeal nerves, and obviously the sympathetic trunks as well. So the bronchial tree at the carina will branch into the right main bronchus, and the left main bronchus, the right is wider and shorter and more vertical, so it's where your tend to find aspirated objects here, and on the left is a little bit longer, more narrow and more doubly, and then so that's the primary bronchial, the secondary or lower bronchial, and there's three on the right, the upper, middle and lower, on two on the left, the upper and lower, and so they correspond to the lobes of the lung. Then you're going to have segmental or tertiary bronchial, which supply the bronchial pulmonary segments. The bronchial pulmonary segments are the smallest functionally independent unit of the lung. Each has its own segmental bronchus and segmental branch of pulmonary artery. Veins run in the connective tissue between the segments. The relevance of that technically is that infections or aspirated objects can often localize two specific segments, and generally surgical resection can remove one segment without effecting the other, so you've got tan of those in the right lung and it tan in the left lung. The other two was the outline the histology of the normal airways on the lungs, so in the track here as mentioned, you're going to have the respiratory epithelium, which is associated pseudo stratified columnar epithelium with goblet cells, the goblet cells produce mucus on the cilia, facility and mucus ciliaary clearance, and you'll also have laminopropria, which is loose connective tissue that's rich in elastic fibers, you'll have the sub-micosa, which is zero mucus glands, which produce mucus and waterase secretions, you'll have your c-shaped hairline cartilage rings, which are opened posteriorly, and you'll also have the adventisha, which binds the trachea to the exterior structures, and then the trachea muscle at the close end of the posterior duct, so the bronco epithelium will be much the same as the trachea, so the respiratory epithelium, the sub-micosa will have fewer glands compared to the trachea as you go down, so you'll have cartilage, but there'll be more glands, and that full rings, and the most prominent layer will be the smooth muscle, which encircles the limb, and this is in the bronchi, in the bronchioles, for the larger ones you'll have the ciliated columnar epithelium with few goblet cells, but in the smaller you'll just have ciliated cuboidal epithelium, you will have specialized cells in there as well, you'll have flara or club cells, which are domeshipped non-celliated secretory cells, which detoxify harmful substances, secrete surfactant components, and the regenerate epithelium, you'll have no cartilage in the bronchioles, no serum ucus glands, and again, prominent smooth muscle, which controls the calibre of the airway, then you'll have the terminal bronchioles, and the simple cuboidal epithelium, mainly club cells, and some ciliated cells, and their function is the last part of the conducting zone, so the conducting zone is obviously where there's no gas exchange, then you'll pass into the rep respiratory bronchioles, the epithelium changes from cuboidal to squamous, and the special feature here is that it's the first site of a alveoli budding from the alveoli walls, Morgana's start of the gas exchange, then you'll have the alveoli ducts and the alveoli, alveoli walls are lined by two me and epithelial cells, you've got type one pneumocytes, which are flat squamous cells, you'll cover around 95% of the surface, and these are for gas exchange, and you'll have the type two pneumocytes, which are cuboidal cells, and secret pulmonary surfactant, which reduces surface tension, prevents allular collapse and serve as progenitors, you'll also have alveolar macrophages or dust cells, which are mobile immune cells, which remove disease, irritable debris, and pathogens, then you've got the capillary network, which is an extremely thin barrier formed by the type one pneumocytes, the fused biazolamina and the capillary endothelial cells. L'Op3 was to distinguish between the bright and the left lung, including the hyalur with reference to gross anatomical features, so the right lung obviously has three lobes, the upper metal and lower, with the two fishers, oblique fishers separate in the lower lobe from the upper and the metal, and in the horizontal fishers separate the upper from the metal lobe, the left only has two, the upper and lower, and one oblique fisher only. It also has a cardiac notch in the upper lobe, and a lingula, which is a tongue-like projection of the upper lobe, analogous to the right metal lobe. So the borders, the anterior border on the right will be straight, but on the left will be notched due to the cardiac impression or the cardiac notch. The posterior border are both rounded, which lie alongside the pervertible column and the inferior border, both sharp and separating the base over the diaphragmatic surface from the causal surface, and just on the surfaces you've got the convex causal surface, which is related to the ribs and inner causal spaces. You've got the medius dynal surface, which on the right has impressions for the superior and inferior renicava, the right etrium, the esophagus, and the azagasvene, and on the left it has impressions for the heart over the cardiac compression, the aortic arch, the thoracic aorta, the left subclavian artery, and at the base I was mentioned you have the diaphragmatic surface, which is concave and sits on top of the diaphragm. The highlam is the region on the medius dynal surface where bronchi, vessels, lymphotics and nerves enter and exit. On the right hi-lim or the right root, the order from top dyn will be on the superior surface will be aparterial broncus, which is going to the upper lobe and lies above the pulmonary artery. So you add in the middle you've got pulmonary arteries and inferior pulmonary veins, the superior and inferior. So the pneumonic there is Bav, so this is the right highlam Bav, concus artery veins from top dyn, and you've got then the vagus nerves, which pass immediately posterior to the lung root on the freinic nerves, which are immediately anterior. You've also got the pulmonary ligament, which is a fold of the pleura that protect the project inferiorly, from the root of the lung to stabilize the inferior lobe and prevent movement during respiration. Even on the left hi-lim or the left root, the order from above dyn is the pulmonary artery. The left main broncus and then the pulmonary veins. So here you've got the pneumonic ABV, artery broncus veins, so right side Bav, left side ABV. The chest cavity is divided into medium and lateral partitions. The median is the medius thinum, and the lateral or the pleura and the lungs. The medius thinum extends to the root of the neck above, known as the thoracic inlet, the diaphragm below the sternum anteriorly and the vertebral column posteriorly. The sternal angle, which is the connection between the sternum and the menubrium, the marked the superior and inferior medius thinum, the lobe vibe was to discuss or describe the blood supply and venus drainage of the bronchi and the lungs, so to note here that the lungs have two distinct circulations, the pulmonary and the bronchial. So the pulmonary circulation is the functional supply for acid change by the arteries of the pulmonary trunk arise from the right ventricle, which divides into the right and left pulmonary arteries and enter into the lung at the highlam, the branch alongside the bronchi and end and capillary networks around the alveoli, so you deliver the oxygenated blood for oxygenation. Then the venus, and you have two pulmonary venus from each lung superior and inferior, which drain oxygenated blood into the left ear trim. Nutrational supply. fly in the bronchial circulation, right from the thoracic aorta. On the intercostal arteries or thoracic aorta branches, there will be usually two branches on the left from the thoracic aorta, one on the right from the intercostal arteries or thoracic aorta branches. These supply the bronchial walls, the connective tissue, the visceral plura, and the large pulmonary vessels. The vians then drain partly into the azagos system on the right, and then the azagos or superior intercostal vein on the left, and this constitutes systemic venous return. Some also drain directly into pulmonary veins, reading a physiological right to left shun, which is slight mixing of deoxygenated blood, and just a touch on the clinical correlation here before we move on. In hemopthesis, you have massive bleeding, which usually arises from the bronchial arteries, so systemic circulation and high pressure, rather than the pulmonary circulation, and then in a pulmonary embolism, you have a clot, which lodges in the pulmonary arteries, leads up to blockage of functional circulation, but lung tissue may survive because of the bronchial so on the the PBL lobs, and log six, we're to define asthma and outline its prevalence in the UK. Spazema is a chronic, inflammatory disorder of the airways characterized by variable, reversible air flow obstruction, and airway hyper responsiveness to a variety of stimuli. Its prevalence is about one whale of adults and one and eleven children in the UK, so it's about 5.4 million people treated, and it's more common in children therefore, and also in urban areas, a nice hazard of about 15.6% of prevalence. Lobs 7 was to describe hypersensitivity types and outline the immune mechanisms of different types of hypersensitivity, so just to keep it in relation to the course, you've obviously got there's four types of hypersensitivity, and you have got type one, which is IgE mediated and immediate, which is the one that is concerned with this week's PBL case. You have type two, which is antibody mediated cytotoxic, type three, which is immune complex mediated, and type four, which is detail mediated or delayed, but just for the purpose of this week, we're going to discuss type one, which is the immediate hypersensitivity, one also known specific sensitivity reactions, because they are the ones that are concerned with asthma. So type one, hypersensitivity is the most common and technically important mechanism of allergy. It's immune mediated and involves immunoglobin E, and just on that allergy, refers broadly to an exaggerated or inappropriate immune response to a substance that is normally harmless. For example, pollen, peanuts, or animal boundary. So the steps of immediate hypersensitivity are as follows, you'll have the sensitization phase, which is on the first exposure. So the allergen, such as pollen or protein, enters the body. The antigen presenting cells, such as dendritic cells, bruteses, the allergen, and presented to the TH2 helper T cells. These TH2 cells release cytokines, so interleukin 4, interleukin 5, interleukin 13. Then the B cells are stimulated to switch to making immunoglobin E antibodies specific to that allergen. So IGE binds to the FC RIR receptors on the mast cells, on vasophils, which means that this version is noise-sensitized, so ready to react on re-exposure. The second step is the effector phase, so the subsequent exposures. The allergen is cutered again, and it crossed links IGE on the surface of the mast cells and vasophils. This triggers degranulation, which releases histamine, causes vasodilation, increased vascular permeability, leading to swellness, redness, and itches, leukotrains, brosterglondons, which sustain inflammation, bronchoconstriction, the cytokines, which recruit osinophils and amplify the reaction. The third step is the clinical manifestations, so localized hay fever, such as allergic rhinitis, which is what really knows. Asma, Urdicaria, which is hypes, this can manifest in a fruit allergy, or it can be systemic, so anaphylaxis, which is life-threatening, causes hypertension, airway, swelling, and bronchoconstriction. On the other hand, you've got non-specific sensitivity reactions, so these are allergy-like symptoms, what the immune system, so the immunoglobin AE and the mast cells, and the cross link in et cetera, isn't directly involved. Sometimes called pseudo-allergic, or non-immune, hypersensitivity reactions. You've got the direct activation of the mast cells, without IgA. It can be caused by things like opiates, radiocontrast dyes, which can cause flushing, etching, or bronchosposum. Enzyme deficiencies, or intolerance, such as lactose intolerance, due to lactease deficiency, and it's not an allergy, so it's just an enzyme deficiency. You can also have pharmacological sensitivity, so aspirin or NSAID, sensitivity, so they lead to the inhibition of cyclooxygenase, which is a key enzyme, in the conversion of arachidonic acid into important signaling molecules, called flustic landans and thromboxins. We had Hepat-CUX, which is an enzyme and conversion of arachidonic acid into important signaling molecules, called flustic landans and thromboxins. This leads to shunting towards lucutrine production, leading to bronchosposum and susceptible individuals. This is in this aspirin exacerbated respiratory disease, and you can also have erotent effects, so some foods are additive, such as sulfates, or AMSG. It can cause flushing, wheeze, or abdominal upset. Nope, it is two described as symptoms and signs of early controlled asthma. The symptoms will include polyphonic and expiratory wheeze, a cough, which might be worse at night or early in the morning. Chess, tightness, episodic breathlessness, the worsening of symptoms at night or early in the morning, symptoms that are triggered by allergens, exercise, cold air, or infection. The signs would be, as mentioned, the widespread expiratory wheeze, baccabinia, or tachycardia, paper-inflated chest, this will be in phonic asthma, and in extreme cases, the use of accessory muscles for respiration. So, top nine was to describe the investigations that can be used to confirm the diagnosis of asthma, including the diagnosis of allergy. So, for diagnostic investigations for asthma, history, and examination are essential. You've got objective tests, which are for adults and children greater than five years old. So, that would involve things like spirometry with bronchodilator reversion fluid. So, if the FEV1 and the FVC ratio is less than 70%, there is evidence of an obstructive pattern. If there's a greater than or equal to 12%, and 200 ml improvement in FEV1 score after receiving a bronchodilator, then that can be confirmed as asthma. Also, PEF variability of greater than 20% or on a seno, social-actional oxyxyl nitric oxide. This is the quickest, most commonly used test. It'll have a re-issed sanophonic inflammation. And then you've got scimpric or IgE tests, which support allergic asthma. Yeah, and children, mainly its history, PEF, which is peak-expertory flow and reversibility testing, if possible. And they adjust for general allergic sensitization, can be invested again with scimpric testing or serum, allergen specific IgE, with total IgE and the scinophils providing supportive evidence of a topic. The whole plan is to use clinical features to assess the severity of an acute asthma attack. So, the clinical features of the asthma attack would be for a moderate case peak-expertory flow greater than 50% to 75% of predicted. There have been no severe features, like normal speech, if it's severe. So any one of PF, 30 to 50% of the predicted, the respiratory rate of over 25 breaths per minute, and a heart rate of over 110. And inability to complete sentences in one breath. So that's severe. If it's life threatening, the PEF will be less than 33% of what is predicted. The partial pressure of oxygen will be less than 92. And silent chest or cyanosis, exhaustion, confusion, arrhythmia, and hypertension. And we're all very bad signs. And then what to do? And then acute asthma attack. So this is below 11. Apply the emergency management of asthma and a person presenting to accent and emergency. So for oxygen, you want to maintain the salts between 94 and 98%. This will obviously widen our ways. You want a high-dose inhaled sabba, so short-actin beta agonist via a spacer or nebulizer. Then you want to administer oral corticosteroids, such as pleinisolum, or hydrocortism. Man, you can add, if it's very severe, epitrobrium bromide, which is an anti-muscorinic. And then on last stage would be a very severe, you would have magnesium sulfate, or amino acid c-line, or yeah, further on beta-2 agonists. And I'll be more like ICU, ICU admission. So yeah, theofiline, amino philine, magnesium sulfate. But there's a very high side effect, so they would be less likely to use those, unless it was very light-threatening. And log 12, was to explain how your patient with acute asthma should be monitored, following admission to hospital. So after admission with acute asthma patients are monitored with serial PEF-4, companions, oxygen sats, frequent observation of heart rate, respiratory rate, blood pressure, and repeated arterial blood gases, et cetera. And electrolytes and fluid balance are checked, close attention to potassium levels because the doses of beta-2 agonists cause hypokimew. And so I can, for clinical signs of fatigue, reduced consciousness, or a silent chest, or red flags for deterioration, which warns a ICU isolation. So log 13 is to describe the control of respiration and explain common abnormalities of arterial blood gases seen in clinical practice. So breathing is controlled by a balance between neural control centers and chemical feedback. So the neural control centers are located in the medulla and the palms of the brainstem. The medullary, respiratory centers are the dorsal respiratory group, the RD, which is the main rest, inspiratory center, generates the basic rhythm via the phrenic nerve to the diaphragm. The ventral respiratory group then, the other one, VRG, is up to during forced breathing, so expiration of inspiration. And then you have, so they're the medullaries, the DRG and the VRG, and then you have the palm pine centers, which is the pneumotoxic and pneumoustic, which fine tune rhythm and switch between inspiration, expiration. You've got your higher brain influence from the cerebral cortex, which dictates your voluntary control, such as speaking and breath holding. And then you've got the hypothalamus in the limbic system, which are responsible for emotion and stress, which can modify breathing as well. And you've got the chemical control by the chemo receptors. So and the central chemo receptors also in the medulla, they respond to increased partial pressure of carbon dioxide via increased hydrogen ion concentration and the cerebral spinal fluid. And that is the main diver ventilation under normal circumstances. peripheral chemo receptors, so in the carotid and the aortic bodies, and respond to a decrease in partial pressure of oxygen. So less than 8 kilo Pascal's, and or an increased partial pressure of CO2, and increased hydrogen ions, which is important in hypoxic drive, for example, and COPD. So that's your peripherals. And then other receptors to be aware of are the pulmonary stress receptors, which intimidate inspiration when lungs are inflated. So this is known as the herring borough reflex. And then you've got irritant and j-receptors, which respond to things like smoke, dust, or adema, which call it bronchoconstriction, rapid shallow breathing, or cough. So for the ABGs, they reflect the pH, the partial pressure of oxygen, CO2, concentration of bicarbonate. And they're broadly categorized as respiratory acidosis. So the increase in pressure of CO2, decrease in pH, commonly caused by COPD, asthma, or even opus, and compensated for by an increase of the bicarbonate ion in the radial system. Then the respiratory alkylosis is the opposite. So decrease partial pressure of CO2 and increase pH, and be caused by anxiety, pneumonia, or pulmonary embolism. The compensatory mechanism is to decrease the bicarbonate ion through the kidneys. Then you have metabolic acidosis, which is a decrease in the bicarbonate ion and a decrease in the pH, which is caused commonly by renal failure, or lactic acidosis, and also diobatic ketoacidosis. The compensatory mechanism is hyperventilation, so decrease the partial pressure of CO2. And then you have metabolic alkylosis, which is an increase in the bicarbonate ion, increase the pH, and cause commonly by antacids, vomiting, or diuretics. The compensatory mechanism is in pit bokeh ventilation to increase the partial pressure of CO2. So lobe 14 was to describe the putative rules of mast cells, osinophils, lymphocytes, and the attack of allergic asthma on the main mediators they produce. So mast cells have a key role and in that release there are the effector cells, and they are activated when the allergen process links, IgE, to bind FC, Epsilon, RI1 receptors, which is high affinity for IgE. The effects here are bronchoconstriction, mucosal edema, and exweast mucous secretion. The main mediators are immediately, which are pre-formed in the mast cell, or histamine, and septes. And then minutes after you'll have newly synthesized mediators, such as lookatreins, LTC4, LTD4, and LTE4, rosterglandin D2, latelet activating factor, and the cytokines so TNF alpha, IL4 and IL5. Osinophils are the major players in the lead phase response, 48 hours after the allergen exposure. They're recruited and activated by the TH2 cytokines, particularly IL5 and IL13. The effects are tissue damage, so epithelial cell injury, they perpetuate airway hyper-responsiveness, and they contribute to chronic inflammation and remodeling. The main mediators are toxic granule proteins, so MBP, or major basic protein, ocenephal cationic, ECP, or ocenephal heroxidase EPO. The cytokines involved as mediators are, as mentioned, IL3 and IL5, and the lookatreins, especially LTC4, as well as IL5 and IL13. The cytokines being involved in ocenephalic recruitment, they've also got the GMCASAS, which is granulocyte, macrophage, colony, stimulating factor. So lastly, the lymphocytes, the T cells, especially the TH2 cells, play a role as orchestrators of the immune response. The TH2 subset drives the allergic phenotype, so the effects are that they promote IgE production by B cells. They recruit and activate ocenephals on mast cells, and they maintain phonic inflammation. The main mediators are IL4, which promotes B cell class switching to IgE, IL5, which is important for ocenephal growth, recruitment, and activation. IL13, which is responsible for goblet cell hyperplasia, Eugus hypersecretion, an airway hyperreactivity, an IL9, which is important in mast cell proliferation. L15 was to list the precipitate flakers including drugs for an asthma attack, asthma attacks can be precipitated by allergens, respiratory infections, exercise, cold air, emotional stress, gastroesophageal, reflux, and occupational exposures, drugs such as non-selective beta blockers, and cells or aspirin, and AS inhibitors. What's more important, I like the genic. Lookers, I learned that chapter 16 was to explain the mechanisms that increase airway resistance and asthma and why they relate to the pathological changes of the airways. So, the first one you've got bronch- bronch- bronch- restriction, which is smooth muscle contraction and responds to the mediators. Two is airway wall odema from inflammation and increased vascular permeability. You've also got a third, which is Mika's hypersecretion, which plugs the airways. And then finally, fourth, and chronic disease, you might have airway remodeling, which is the thickened basement membrane and smooth muscle hypertrophy. This is a less reversible obstruction. So, lobe 17 was to compare the mechanism of action, the root of administration, the place and therapy and the major side effects of asthma treatments, including short and long acting beta-2 agonist, corticosteroids, anti-muscular antichrugs, methyl-santine derivatives, e.g. immunophylline and lipatrine receptor antigonists. So, the treatment of asthma falls between relief and preventant, so consultant. So, but now it's kind of any new patients, over 12, the nice guidelines stipulated that they'll be subscribed a low dose management on relicant treatment or maintenance and reliever therapy or marked as such as a new decenite or four-matteral. But generally, you'll have the reliever therapy, which is your short acting beta-2 adrenary receptor agonists or sabba, such as subunimal. The mechanism is the beta-2 agonist, because of the smooth muscle to relax, leading to bronchidylation. And the root is inhaled. The side effects may be the summer, like a cardio or hypokillinia, and the preventer on the controller and different increasing levels of severity of asthma. It's about your low-dose inhaled corticosteroid. So, that's ICS, such as feclumethism. The mechanism reduces the airway inflammation, and the side effects can be oral thrush or horse voice. And if that doesn't help, you would add lava, so long acting beta-2 agonist, such as sub-matteral or four-matteral. It's not controlled with inhaled corticosteroids or ICS alone. The mechanism, it is a long standing, sorry, a long acting beta-2 agonist, leading to sustained bronchidylation. And the side effects will be tremor, palpitations. But you would never really use this without inhaled corticosteroid first. So, it's the third step wise. Advancement of that would be to increase the inhaled corticosteroid dose, and/or add other agents. So, you've also got the LTRAs, the luketrain receptor, I guess, such as Monte lukest, which blocks the luketrain receptors. But this cannot cause mood changes. And you've got theofiling, which is a false-food diastery as an inhibitor, and back to the bronchidylater, but can have severe side effects of nausea, arrhythmia, and seizures. So, this will be only for ICU, not commonly used. And then you've got long acting muscarinic antagonists, such as tiotropium. And these can also cause bronchidylation, but again, very advanced stage of acute asthma. And then in very severe cases, you have biologics, so which is omalazab, or meppolizmab, meppolizmab. Yeah, so that's anti-IG and anti-interlucant 5 compounds, but very, very severe and very rarely used. What 19 is to discuss drugs on their mechanism of action using the pharmacodynamics and pharmacokinetics of aspirin and opiates as examples. So, drugs act through their pharmacodynamics, which is their mechanism of action and their receptor effects, and their pharmacokinetics, which is their absorption, distribution, metabolism, and excretion. To use aspirin as an example, or also known, well, aspirin is the used name, but it's a Cetyl salicylic acid. The mechanism of action, so it's pharmacodynamics and irreversibly inhibits cyclooxygenase enzymes, COX-1 and COX-2, leading to decreased borosol glandin and thromboxin synthesis. COX-1 inhibition results in reduced thromboxin A2, leading to an anti-platelet effect, and COX-2 inhibition is reduced across the glandin, so anti-inflammatory, analgesic, and anti-pirate effects. So, the results here is pain relief, fever reduction, anti-inflammatory, and anti- thrombotic, but the adverse effects would be gastric irritation, ulceration, bleeding, and tenitis in high doses. Now, the pharmacokinetics, so that's the absorption, distribution, metabolism, and excretion. So, absorption is rapid from the stomach and the small intestine. The distribution is widely distributed, it binds plasma proteins, metabolism, it's mainly in the liver, so it's hydrolyzed into salicylic acid, excretion then. Through the kidneys, it's a half-life of about two or three hours, which is short, and as long as the high doses due to saturation of metabolism. Now, to use opiates, for example, morphine, the pharmacokinetics, so the mechanism of action, it acts as an eigenest at the opioid receptors, so you've got mu capa and delta in the central nervous system on the peripheral tissues. So, the mu receptor activation results in analgesia, euphoria, respiratory depression, sedation, reduced GI motility. That's respiratory depression, not depression. You've got a copper subracnovation, which results in, again, analgesia, sedation on dysphoria. dysphoria is a mental state, in which a person has a profound sense of unease or dissatisfaction. So, the effect here would be pain relief, sedation, cough suppression, and constipation. And the adverse effects would be respiratory depression, nausea, vomiting, constipation, and dependence. Pharmacokinetics, so the absorption would be oral, IV, subcutaneous, intramuscular, the bioavailability varies. So, the first pass metabolism reduces the oral bioavailability. The distribution crosses the blood brain barrier, distributes the CNS, the kidneys, and the lungs. The metabolism, it's metabolized, epatically. So, fee is one in two reactions, mainly, the cure in the nightation, and excretion is renal. So, through the year, a year, and it's a half life of about two to four hours for morphing. The lop-20 is to describe the physiology of respiration and explain how it changes in the airway resistance and lung compliance, alter, inspiration, and expiration. So, just to quickly summarize this, there was a lecture given, but the details are there in the notes. In general, respiration depends on the balance between alveolar pressure, introplural pleasure, airway resistance, and lung compliance. Increased airway resistance, as in asthma, impedes the air flow, especially during exploration, while decreased lung compliance, as in fibrosis makes inspiration more difficult. Both alterations increase the work of breathing and affect ventilation efficiency. Lop-21 is to differentiate between obstructive and central sleep up near. So, sleep up near is the temporary cessation of breathing during sleep. Ventilation decreases during sleep or wakefulness to sleep. So, when you go from a wakeful to a sleep sleeping state, there's a decreased metabolic rate. So, a decreased respiratory demand. The postural changes alter the breathing mechanics. So, you've got a decrease in the sympathetic nervous system and an increase in the parasympathetic nervous system tone, which equals lower heart rate, low pressure, and cardiac output, decreased tidal volume, decreased respiratory rate, and decreased minimum volume, a decrease in saturation of O2, an increase in saturation of quarter dioxide, a general decrease in the upper airway colour. So, with that said, sleep up near is characterized by greater than five episodes per hour of greater than 10 seconds. So, it's obviously the stopping of breathing for 10 seconds, if it's higher than five times an hour, that'll be sleep up near. It can be as high as 160 times an hour of greater than 90 seconds in the variant severe cases. tiredness. So obviously for per sleep cardiovascular complications due to activated sympathetic nervous system and stress. And yeah, so obesity and diabetes and inflammation and metabolic dysfunction all involved. And so the difference between obstructive and central sleep out near. So obstructive sleep out near is a blockade of the upper respiratory tract during sleep. The displacement of the genial glossis which is the main tongue muscle leads to increased pressure on the neck due to fat deposition. And the relaxation of the pharyngeal dilator muscles obstructs the upper airway. So the risk factors for obstructive or obesity, alcohol, sedatives and smoking. Whereas central sleep out near is a dysfunction in the process that initiates breathing. So this can be due to stroke. So the damage of the respiratory centers and the brain can be due to drugs such as opioid which is suppression of neuronal activity to be to do with central hypoventilation syndrome and maybe as a result of injury or trauma to the brain stem or congenital in neonates. So the continued development of the respiratory centers. And altitude. For example, Shane Stokes Respiration which is oscillating up near and hyperpnea. So just briefly on log 20, then describe the normal process process of control of breathing. So within your respiratory center, you've got your Rhythmicity area on your new mutoxic area. And in the Rhythmicity area you've got the ventral respiratory group and the partial respiratory group. And they're both connected by nerve impulses to the diaphragm on respiratory muscles. The dorsal usually facilitates normal breathing on the ventral with facilitated forcible breathing. And in the new mutoxic area, they have connections to nerve impulses which regulate the rate of breathing on the transition from inspiration to expiration. So they would tend to feed into the dorsal respiratory group. The last log was to perform an interpretive peak flow sparametry and understand the measurement of transfer factor. And so just on this, FVC, the force vital capacity is the total Axial, after maximal inhalation. FV1 is the forced expatory volume in one second. And then the ratio is key in distinguishing between obstructive and restrictive disease. So in an obstructive pattern such as asthma or COPD, you'll have produced FV1. The FV1, the FVC ratio will be less than 0.7. But the FVC will be normal or slightly reduced. And so we've touched on the reversibility test. So that's FV1. It's greater or equal to 12%. And 200 mills after the brongo-dialiter after the initial reading, then asthma is likely. So but the restrictive pattern such as fibrosis or obesity is decreased FVC. And FV1 is reduced proportionally. So the ratio will be normal. And that's how you tell if it's restrictive or opposed to obstructive. The restrictive FV1 the FVC ratio will be proportional. So normal or even increased. So a transfer factor wasn't mentioned in PBL, but it's in the lobbyists. So the purpose of transfer factor, or DSTLCO, is to measure the diffusing capacity of the lungs for carbon monoxide. It reflects the ability of the alveolar capillary membrane to transfer gas into the blood. It's useful for interstitial lung disease and pacimate pulmonary vascular disease. So the patient inhales a small concentration of carbon monoxide to the total lung capacity. Holds the breath for 10 seconds. Exhale's, and then the concentration of carbon monoxide in axial gas is measured. And the DLCO is calculated to the amount of carbon monoxide absorbed per unit time per alveolar volume. The interpretation ends so low DLCO, which suggests a second alveolar capillary membrane, potential fibrosis or sarcoidosis, potential loss of alveolar surface area, which is known as the emphysema, or pulmonary vascular disease, or reduced pulmonary blood flow. Normal or increased blood spher factor, may indicate that asthma may have normal or slightly increased DLCO due to increased pulmonary blood volume. So the clinical skills I am in this week's lobes are to do with the respiratory history. So a lot of the ops covered in class and I'm happy enough with it. So I'll just go over the respiratory exam. So the first stage is the introduction. You introduce yourself. Check the patient ID, wash your hands, explain the procedure, gain consent, and position the patient, and expose them appropriately. Here you want to have good monitor, avoid specialist terms, and have a succinct description of the chest exam in suitable detail. Then you follow the end of bed check. You're looking for artifact clues for respiratory problems, such as oxygen, inhalers, IV, as the patient is well enough to continue, so able to speak and not to stress, or the accessory muscles in use, note that that's also in the nostrils, not just the um the castles or the abdomen. Then you can ask the patient to put their hands out, and you're checking for lobbing, cyanosis, toer staining, thin skin, or bruising, which is indicative of steroid use, Eda Eugenus tremor, CO2 flop, and holes which should be between 1600 and the respiratory rate, which should be between about 12 and 20. Lobbing is associated with chronic pulmonary diseases, such as lung cancer, bronchiac classes, fibrosis, cyanotic heart disease, astrointestinal and hepatic disorders, such as IBD and cirrhosis, endophanem disease, such as thyroid acropagy, such a result, it's thought to be a result of vascular and connective tissue proliferation mediated by vascular endothelial growth factor and hypoxia. Then you'll move on to the face, there's five things here, so you're inspecting for cyanosis, platyric, you're like inflated, so cyanosis is like blueness, and platyric is sort of swollen face, you're inflated looking, three is polar, four is per slips and five is hornar syndrome, so cyanosis can be caused by severe asthma, COPD, pneumonia, pulmonary embolism, interstitial lung disease, and cyanotic chronic heart disease, hurting the inner heart disease, sorry, etheric is caused by chronic hypoxia, eating two secondary polycythemia, such as COPD and cyanotic CHD, polar is caused by anemia, chronic illness, acute blood loss, acropaxia, first slips can be a symptom of COPD, emphysema, chronic bronchitis, asthma, exacerbation, and hornar syndrome is indicative of a lung coast or epical lung shimmer, and so an obsessed compress in the sympathetic chain, then you'll move on to the neck, it's going to be the lymph nodes, so you work through the groups of lymph nodes systematically comparing the left to the right and pressing down firmly, the groups you're looking for are sub-mental, sub-mandebular, anterior and posterior triangle, gree-imposed or regular, the occipital and the super-clificular, here you can also check for the JVP, but that's also part of the coronary and cardiovascular, sorry, so then you move on for your chest inspection, I'm here looking at four short sub-rath, the respiratory area, any sort of pattern associated features such as wheeze or strider, and the shape of the chest, so you can have pectus x-cavatum, which keeps in or pectus carinatum, which pops out, you're also going to look for symmetry and scars, make sure to check that axola, so under the arms, and yeah just note that crackling can indicate infection or pneumonia. Then you're going to move on to palpation, so that's to do with the trachea and the chest expansion using thumbs, so you feel in the tracheal notch using three fingers, your middle finger to feel your index and your ring finger used to rest on the clavicles, your check in here for like pneumothorax, which is a collection of air in the pleural cavity that can cause tracheal deviation, and then through the chest expansion, you want symmetrical firm grip on the chest wall, and the patient breathes in, and you watch your thumbs for uneven expansion, you move with the ribs, upwards and backwards, avoiding sliding over the skin, then you're going to percuss, so you do the long fields, anterior and posterior if possible, and you begin 2.5 centimeters above the clavicle and percuss at least every second, intercostal space, move the wrist, you're checking for cardiac doneness, and you'll know you've got to the bottom of the lungs when you've got to the the upper. limit of the liver dollus. So the end oscillation, you're looking at for air entry, the character of the air and the added signs. So if it's vesicular, it's going to be soft, low-pitched, predominantly in spiritory. And it's appreciated especially well at the posterior basis of the lungs. So that's vesicular, whereas bronchial air signs are lighter and occur closer to the trachea. Crapitation is popping or crockling sign, indicative of bronchitis, pneumonia or pulmonary embolism. The rub is like a squeaking of a shoe and can indicate pleural inflammation, PE or pneumonia. And we want to make sure to also see it all areas including the apex. Then just check the legs, you're looking for the evidence of DVT, which will show a swelling, redness or warmth, and also pitting oedema, which is the indentation remaining after you press time. You also want to close the exam appropriately. Let's thank the patient. And yeah, just be aware of that as well. It's an important part of the exam. So just to touch on some of the PPS lobes that were given at this week, 30 was to identify the major differences in disease risks over time and between places. This one was to recognize that disease prevalence, incidence and mortality vary geographically and temporally. For example, cardiovascular disease is higher in western countries and malaria is prevalent in tropical regions. Another example would be that lung cancer incidence rises in some countries over decades due to smoking trends. The key idea is that disease risk is dynamic. It's influenced by environment, lifestyle, health care, access and genetics. Lobe 31 was to interpret geographic and temporal variations, distinguishing artificial versus real differences. Real differences they reflect true variation in disease burden. For example, higher TB rates in low income countries due to crowded living conditions. Artifactual differences may result from measurement, reporting or diagnostic differences, so not true risk. For example, improved cancer registries may show as an increase in incidence. The key idea is that critical evaluation of data is needed to avoid misinterpretation. 32 was to analyze how variations in disease risk inform understanding of causes and treatment. So observing the patterns over time and place helps to generate hypotheses about disease ideology and risk factors. For example, migration studies which show changes in diabetes prevalence can lead to or be informed by lifestyle influences. This can inform public health planning and therapeutic strategies based on population specific risks. The key idea here is that epidemiology links disease patterns to causal inferences and that informs treatment prevention. So understanding how disease risk varies by time and place helps identify real versus artifactual differences, generate hypotheses about causes and guide prevention and treatment strategies. Lobe 33 was to explain the ethical and legal significance of the concept of consent in clinical practice. So consent is the patient's voluntary agreement to treatment, examination or other aspects of health care and appearance, permission to examine, investigate or treat the waving of a right to bodily integrity. So there's three real domains of consent and their capacity informed and voluntary. Note that consent should also be continuing and that is patients should know when it can change their minds and it can be explicit or implied consent. So the legal basis of consent can be found in court law, criminal law, statute law and common law. So capacity, the mental health, mental capacity and I act 2016. And there's a presumption of capacity for those over 16 capacity is decision time specific and involves full support for decision making. You cannot judge on age or appearance. It is task and time specific. Irrational or unwise decisions are not evidence of end capacity. A burden of proof to demonstrate lack of capacity is balanced of probabilities. So open quotation marks, taken reasonable steps, those have open reasonable belief. So whether someone is able to make a decision or not is to be determined merely on the basis of any condition that the person has or any other characteristic of the person which might lead others to make unjustified assumptions about his or her ability to make a decision. We'll read that again. Whether someone is able to make a decision is not to be determined merely on the basis of any condition that the person has or any other characteristic of the person which might lead others to make unjustified assumptions about his or her ability to make a decision unless all practicable, practicable help and support to enable the person to make a decision about that matter has been given without success. Section three of the mental capacity and I act 2016 states that if at the material time the person is only able to make a decision for him or herself about the matter because of an impairment of or a disturbance in the functioning of the mind or the brain. Only able to make a decision means is not able to understand the information relevant to the decision is not able to retain that information for the time required to make the decision and is not able to appreciate the relevance of that information and to use and weigh that information as part of the process of making the decision and is not able to communicate his or her decision whether by talking using sign language or any other means. So that's capacity informed and this hinges on the Montgomery case which is the case that established informed consent is not about what doctors think patients should know but about what patients need to know to make an informed decision. So it follows a P-A-R-Q format in a lot of cases which is procedure, alternatives, risks and questions. So prior to Montgomery we had the volume standard which was the lies in 1957 which states that a doctor is not guilty of negligence if he or she has acted in accordance with the practice accepted as proper by a responsible body of medical doctor skilled in that particular art in Cidaway 1985. It was argued that whether a doctor in a mission to warn a patient of risks of treatment was a breach of the duty of care was normally to be determined by the application of the volume test i.e. whether the admission was accepted as proper by a responsible body of medical opinion which could not be rejected as irrational. The doctor is under duty to take reasonable care to ensure that the patient is aware of any material risks involved in proposed treatment and of reasonable alternatives. A risk is material if, in the circumstances of the particular case, a reasonable person in the patient's position would be likely to attach significance to the risk or the doctor is or should reasonably be aware that the particular patient would be likely to attach significance to it. So that's informed. The voluntary. Patients must be able to review, excuse and they must know about disability. Patients must be free from undue pressure i.e. free from coercion and perceived coercion. The problems of informed consent, they include the presentation of information, complexity of information, medical uncertainty, the effect of fear, illness and social status of the doctor, embarrassment, cynical environment on decision making and consuming. And when the individual does not have capacity and is not an emergency, then the common law necessity principle, advanced directives and best interests are in effect in that order. So advanced directives and best interests, and in England and Wales the last thing of part of attorney come for best interests, also the part on capacity where unable to make a decision means is not able to appreciate the relevance of that information is only an N.I. So what is meant by best interests then, that means that the decision cannot be made merely on the basis of age, appearance or any other characteristic consideration of all relevant circumstances, including whether at some time the individual will have capacity to make their own decision and when. Support the decision making of the individual. Have special regard to the wishes, feelings, beliefs and values that would likely influence our person's decision and other factors they would consider. The consultation of the relevant people, so the person is caring for the family advocates and take into account those views, take in the least restrictive approach in relation to the patient's rights and freedom of action and whether failure to act will result in harm. And if life saving treatment must not be motivated by a desire to bring about death, that's that for consent. (upbeat music)