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Primary FRCA Regional Teaching Day - SBAs. Vivek Sinha ST4 Anaesthetics HRI 11/05/2013. Physiology.
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Primary FRCA Regional Teaching Day - SBAs Vivek Sinha ST4 Anaesthetics HRI 11/05/2013
Physiology • 1) A patient on the intensive care unit is being ventilated in a volume-controlled mode with an FiO2 of 0.6. Arterial blood gas analysis reveals a PaO2 of 7.5kPa and a PaCO2 of 4.7kPa. Which ONE of the following is the best intervention aimed at increasing the PaO2? • a) Increase the FiO2 • b) Increase the tidal volume • c) Increase the frequency • d) Increase the inspiratory time • e) Increase the expiratory time
Physiology • 2) A hormone is produced in the cytoplasm of an endocrine cell and is then stored in granules within the cytoplasm. On release from the cell it is carried in the blood-stream to a target cell, where it crosses the cell membrane and binds directly to the nucleus, increasing cell gene transcription. Which hormone is best described in these terms? • a) Adrenaline • b) Thyroxine • c) Aldosterone • d) Thyroid-stimulating hormone • e) Growth hormone
Explanation3 main Classes of Hormone • Peptides (eg. Growth Hormone) • Synthesised in cell nucleus and then stored in granules and released by exocytosis • Surface receptor • Act via second messengers • Amines • Synthesised in the cytoplasm and then stored in granules • Two sub-types: • Catecholamines (eg. adrenaline) – act at cell membranes and use second messengers • Thyroid hormones (eg. Thyroxine) – binds directly to nucleus receptors, stimulating transcription • Steroid (eg. Aldosterone) • Synthesised from cholesterol • Immediately released (not stored) • Lipid-soluble • Enter cytoplasm and typically bind with receptors there and then enter nucleus to stimulate transcription
Explanation • Adrenaline & TSH – Gs protein-coupled receptors • T3 & T4 stored in follicle stems between thyroid cells as the protein thyroglobulin • 33% Thyroxine (T4) converted to T3 in target tissues and 45% to Reverse T3 • T3 acts on nuclear receptors to alter cellular function via messenger RNA • T4 has much less affinity to nuclear receptor
Physiology • 3) A patient with chronic obstructive pulmonary disease presents for assessment for long-term oxygen therapy (LTOT) and is found to have a compensated respiratory acidosis. Which of the following sets of arterial blood gases best demonstrates compensated respiratory acidosis? • a) pH=7.30, PCO2=7.2kPa, PO2=9.5kPa, HCO3-=25mmol/L • b) pH=7.36, PCO2=8.5kPa, PO2=7.5kPa, HCO3-=43mmol/L • c) pH=7.24, PCO2=10.1kPa, PO2=7.0kPa, HCO3-=27mmol/L • d) pH=7.24, PCO2=3.5kPa, PO2=8.5kPa, HCO3-=18mmol/L • e) pH=7.20, PCO2=6.2kPa, PO2=9.0kPa, HCO3-=15mmol/L
Physiology • 4) Which of the following statements regarding humoral mechanisms involved in controlling haemorrhage is INCORRECT? • a) Circulating catecholamines increase • b) Atrial natriuretic peptide (ANP) levels increase • c) Vasopressin release is mediated via the Gauer-Henry reflex • d) Stimulation of the adrenal cortex promotes release of aldosterone • e) Circulating levels of enkephalins increase
Explanation • Aldosterone • Secreted by zona glomerulosa of adrenal cortex • Major regulators • Renin-angiotensin system • Plasma concentration of potassium • ACTH • Miscellaneous regulators • Sympathetic nerves • Baroreceptors • Plasma concentration of sodium • Aldosterone feedback
Explanation • Enkephalins and endorphins • Endogenous opioids that bind to and activate opioid receptors throughout the CNS • Levels of enkephalins increased when adrenal medulla is stimulated • Gauer-Henry reflex • Atrial stretch sensors sense decrease in volume and transmit signals to increase ADH secretion • Gravitational change from 1g to microgravity may cause cephalad fluid shift, resulting in suppression of ADH secretion and diuresis
Explanation • ANP • Plays important role in blood volume and electrolyte homeostasis in normovolemia and in hypervolemic states • Secreted primarily from atria • Hypervolemia and elevation of left atrial pressure or volume are the major known factors stimulating its release (local wall stretch) • Plays important role in blood volume homeostasis by inducing rapid natriuresis and water excretion • Lowers BP and antagonises renin-angiotensin-aldosterone axis • Mild bleeding induces a rapid decrease in ANP secretion • Some studies show increased plasma ANP after prolonged severe haemorrhage (possible biphasic effect of haemorrhage)
Physiology • 5) A farmer slips and falls in a remote field during a hot summer. He has nothing to eat and his only drink is whisky from a hip flask. He is not found for 3 days. On admission to hospital he is peripherally cold, with a heart rate of 110 beats/min and a blood pressure of 85/40mmHg. Which of the following is the most potent stimulus for antidiuretic hormone release? • a) Stimulation of central osmoreceptors • b) Stimulation of aortic arch baroreceptors • c) Ingestion of alcohol • d) Pain • e) Stress
Explanation • Alcohol inhibits ADH • Pain and stress stimulate ADH • Osmoreceptors are very sensitive • They respond to a change as small as a 1 to 2% increase in tonicity • Baroreceptors are less sensitive (but more potent) than the osmoreceptors • Hypovolaemia is a more potent stimulus for ADH release than is hyperosmolality. • A hypovolaemic stimulus to ADH secretion will override a hypotonic inhibition and volume will be conserved at the expense of tonicity
Physiology • 6) Prior to induction of anaesthesia you preoxygenate the patient with a Bain circuit and a close fitting mask for 5 min. The reason for this is: • a) To increase dissolved oxygen in the blood • b) To flush out nitrogen • c) To increase FRC • d) To increase oxygen Hg capacity • e) To increase the amount of oxygen in the alveoli with 3l
Explanation • Dissolved oxygen plays a tiny part in oxygen content and transport compared to haemoglobin. • 100ml of arterial blood contains approximately 20ml of oxygen, 19.7ml of which is combined with haemoglobin, whereas only 0.3ml is dissolved in plasma. • In venous blood these figures are 14.9 and 0.1 respectively. • The oxygen content equation is as follows: Oxygen content = (1.34 x Hb x sats)/100 + 0.023pO2, where the Hb is measured in g/dl and the pO2 is measured in kPa and the solubility coefficient of O2 is 0.023 ml/dl/kPa.
Explanation • In normal person breathing room air with Hb 15g/dl, pO2 13.3kPa and sats 97% • Total arterial oxygen content would come to 19.80ml (bound to Hb = 19.497ml and dissolved in plasma = 0.3059ml). • Even if the pO2 is increased to 80kPa • Total oxygen content would rise to only 21.337ml (bound to Hb = 19.497ml and dissolved in plasma = 1.84ml). • This is just a 1.08% rise in total oxygen content • Hyperbaric oxygen chamber
Explanation • 3L lung volume doesn't correlate with any physiological lung measure and alveoli is a very general term when you discuss preoxygenation
Physiology • 7) A 78 year old patient has been admitted to the intensive care unit for intubation and ventilation due to a low GCS. The family give a history of progressive weakness over several weeks with abdominal pain, decreased appetite, confusion and weight loss. The patient is known to have ischaemic heart disease, peripheral vascular disease, glaucoma, prostatic carcinoma and COPD. Blood results have come back showing Hb 9, Platelets 90, WCC 13, Na 149, K 5.6, Ur 14, Cr 220, Ca 3.6. ECG shows a prolonged PR and prolonged QT. • What is the most likely cause of the ECG findings? • a) Congenital • b) Hypercalcaemia • c) Hyperkalaemia • d) Hypernatraemia • e) Myocardial Ischaemia
Explanation • Very rare for a electrolyte abnormality to produce prolonged PR and QT as well - as it needs both conduction and repolarisation to be affected • Hypercalcaemia • Range • Normal serum corrected calcium = 2.1 – 2.6 mmol/L • Mild hypercalcaemia = 2.7 – 2.9 mmol/L • Moderate hypercalcaemia = 3.0 – 3.4 mmol/L • Severe hypercalcaemia = > 3.4 mmol/L • ECG • Main ECG abnormality seen with hypercalcaemia is shortening of the QT interval • ST segment duration shortened • In severe hypercalcaemia, Osborn waves (J waves) may be seen • Ventricular irritability and VF arrest has been reported with extreme hypercalcaemia
Explanation • Typical progressive changes of hyperkalaemia: • Tall, pointed, narrow T waves. • Decreased P wave amplitude, decreased R wave height, widening of QRS complexes, ST segment changes (elevation/depression), hemiblock (esp. left anterior) and 1st degree heart block. • Advanced intraventricular block (very wide QRS with RBBB, LBBB, bi- or tri-fascicular blocks) and ventricular ectopics. • Absent P waves, very broad, bizarre QRS complexes, AV block, VT, VF or ventricular asystole • No significant changes on the ECG occur with hypo-/hypernatraemia
Pharmacology • 8) You are asked to provide anaesthesia for a pregnant woman undergoing emergency appendicectomy. Of the following drugs administered to the woman, which is the least likely to accumulate in the fetus? • a) Bupivacaine • b) Pethidine • c) Thiopental • d) Diamorphine • e) Diazepam
ExplanationPhysiochemical properties • Increased placental transfer • High lipid solubility (eg. Diazepam, most sedatives, pethidine) • MW (<600 dalton for lipid-soluble, <100 dalton for polar) • Bases (LAs & most opioids are weak bases) • Non-ionised (eg phenobarbital) • Low protein-binding • Decreased placental transfer • Acids • Charged (eg. heparin) • Size (heparin, IgM) • Altered or bound by enzymes within placenta (eg. amines, insulin) • Firmly and highly bound to • maternal RBC (eg. CO) • Plasma proteins (eg dicloxacillin, propranolol)
Explanation • Basic drugs • Fetal pH lower (0.1-0.15) than maternal pH • Relatively more ionized than in maternal blood and "ion trapping" may occur, leading to fetal drug accumulation • LAs, Pethidine • However, significant ion-trapping of bupivacaine only occurs in significant acidosis • Pethidine • Pethidine and Norpethidine (active metabolite of pethidine) accumulates in both the mother and fetus with a half-life of 4 and 20 hours respectively in mother and 13 and 62 hours in neonate
Explanation • All used inhalational agents cross the placenta • Very little fetal depression if <1MAC & delivery occurs within 10min of induction • Thiopental, propofol, benzodiazepines and ketamine all cross placenta but only benzodiazepines known to produce significant fetal effects • Diamorphine • Rapidly eliminated by the placenta • Diamorphine, diazepam & pethidine broken down to lipid-soluble products
Pharmacology • 9) A new drug is being tested. Its onset of action depends on the rate of diffusion across the cell membrane. The following factors increase the rate of diffusion of a substance across a biological membrane, EXCEPT which one? • a) Decreased molecular weight • b) Increased concentration gradient • c) Decreased solubility of a gas • d) Increased lipid solubility • e) For a weakly acidic substance, a low environmental pH
ExplanationFactors Influencing Rate of Diffusion • Graham’s Law • Rate of passive diffusion is inversely proportional to square root of molecular size • Fick’s Law • Rate of transfer proportional to concentration gradient across membrane • Ionization • For acidic substance more unionized in lower pH • Lipid-solubility • Protein-binding • Rate of simple diffusion = permeability constant x membrane area x concentration gradient
Pharmacology • 10) An adult patient distressed by shivering in the postoperative period would be most effectively treated with which ONE of the following? • a) Pethidine 25mg • b) Doxapram 100mg • c) Clonidine 150 µg • d) Ketanserin 10mg • e) Alfentanil 250 µg
Pharmacology • 11) After intravenous administration of anaesthesia you notice the area around the injection site has become very swollen, erythematous and inflamed. Which of the following is most likely to cause most damage? • a) Rocuronium • b) Morphine • c) Ondansetron • d) Dexamethasone • e) Thiopental
Hyperosmolar agents Calcium chloride Calcium gluconate Glucose >10% Magnesium sulphate 20% Mannitol 10% and 20% Parenteral nutrition Potassium chloride Sodium bicarbonate Sodium chloride >0.9% X-ray contrast media Acids/alkalis Aminophylline Amiodarone Amphotericin Co-trimoxazole Diazepam Erythromycin Phenytoin Thiopental Vancomycin Vascular regulators Epinephrine Dobutamine Dopamine Metaraminol Norepinephrine Prostaglandin Vasopressin ExplanationDrugs used in anaesthesia/intensive care unit with potential to cause tissue damage Contin Educ Anaesth Crit Care Pain (2010) 10 (4): 109-113.
Pharmacology • 12) You are to carry out an experiment to assess the speed of gastric emptying. A standard dose of a marker drug is to be given to healthy volunteers. You will then measure plasma drug concentration at standard time intervals. Which of the following drugs will be suitable for this: • a) Aspirin • b) Gentamicin • c) Paracetamol • d) Propranolol • e) Vancomycin
Explanation • pH = pKa + log [BASE]/[ACID] • PKa of the drug (Dissociation or ionization constant): • pH at which half of the substance is ionized & half is unionized. • pH of the medium: • Affects ionization of drugs. • Weak acids best absorbed in stomach. • Weak bases best absorbed in intestine. • Aspirin (weak acid), pka=3.0 • Too much absorbed in stomach to be useful as marker • Still absorbed in small intestine despite low unionised fraction, due to large intestinal surface area • Propranolol (weak base), pka= 9.4 • Absorbed mainly in small intestine • Extensive first-pass metabolism • Paracetamol (weak base), pKa=9.5 • Absorbed mainly in small intestine • Paracetamol absorption depends on gastric emptying • Low first-pass metabolism (approx 25%)
Pharmacology • 13) NIDDM patient had a 30 minute knee arthroscopy. Pre-op BM 7. Given Ondansetron and Dexamethasone for PONV. Post-op BM 13. What is the most likely cause for raised BM post-op? • a) Dexamethasone • b) Ondansetron • c) Surgical stress • d) Missed morning dose of anti-diabetic medication • e) Metabolism of Hartmann's fluid
Pharmacology • 14) An asthmatic patient developed bronchospasm from diclofenac. Which one of the following could this be due to? • a) Thromboxane A2 • b) Arachidonic acid • c) Leukotriene • d) Prostacyclin • e) Prostaglandin
Pharmacology • 15) A 25 year old male has just been transferred to the operating table for a repair of an umbilical hernia. After pre-oxygenation and induction of general anaesthesia with thiopentone, fentanyl, mivacurium, an i-gel was inserted and the patient was ventilated with IPPV. A bag of gelofusine was being transfused and remifentanil and sevoflurane used for maintenance of anaesthesia. A dose of teicoplanin was given for surgical prophylaxis. 5 minutes into the surgery the patient develops hypotension, bronchospasm, flushing. • Anaphylaxis was diagnosed and appropriate treatment was started. What is the most likely cause of the anaphylaxis. • a) thiopentone • b) fentanyl • c) mivacurium • d) gelofusine • e) teicoplanin
Explanation • Since 1980 more than 4,500 cases of perianaesthetic anaphylaxis have been reported by French and English authors. • The drugs most frequently responsible for anaphylactic reactions in the French epidemiological survey were • NMBAs (54%) • Latex (22.3%) • Antibiotics (14.7%) • Opioid agents (2.4%) • Hypnotic agents (0.8%) • Colloids (2.8%) • Others (3%) World Allergy Organization (WAO)
Explanation • Among the cases of anaphylaxis attributed to NMBAs in the literature, the following substances have been incriminated, in decreasing order of importance: • suxamethonium, vecuronium, atracurium, pancuronium, rocuronium, mivacurium and cisatracurium. • If one expresses the number of reactions observed in terms of the number of subjects exposed to NMBAs, the drugs can be divided into 3 groups: • those associated with a high frequency of allergic reactions, including suxamethonium and rocuronium; • those associated with an intermediate frequency of allergy, including vecuronium and pancuronium; • those associated with a low frequency of allergy, including atracurium, mivacurium and cisatracurium. World Allergy Organization (WAO)
ExpanationCauses of life-threatening allergic reactions during anaesthesia • Neuromuscular blocking agents (70%) • Steroid-based compounds (vecuronium and pancuronium) cause anaphylactic reactions, whereas benzylisoquinoliniums (mivacurium and atracurium) tend to cause anaphylactoid reactions. • Of drug reactions caused by neuromuscular blocking agents, • 43% are caused by succinylcholine, • 37% vecuronium and • 7% atracurium. • Latex (12.6%) • Colloids (4.7%) • The risk is greatest with gelatin solutions. • All hyperosmolar solutions can release histamine directly. Contin Educ Anaesth Crit Care Pain (2004) 4 (4): 111-113.
ExpanationCauses of life-threatening allergic reactions during anaesthesia • Induction agents (3.6%) • Incidence of severe reactions to thiopental been reported approx 1 in 14000 • Reactions to propofol less common • Least common to etomidate • Antibiotics (2.6%) • Penicillins most frequently implicated • Benzodiazepines (2%) • Opioids (1.7%) • Opioids usually cause anaphylactic reactions; morphine implicated most commonly. • Reactions to synthetic opioids rare • Morphine, codeine and meperidine can cause a dose-dependent, non-immunological cutaneous histamine release • Other agents (2.5%) Contin Educ Anaesth Crit Care Pain (2004) 4 (4): 111-113.
ExplanationIncidence of anaphylaxis according to the NMBA in France over 6 years ( 1997-2002 ) • Rocuronium 1 : 5,100 patients exposed • Succinylcholine 1 : 5,500 patients exposed • Vecuronium 1 : 13,000 patients exposed • Pancuronium 1 : 14,700 patients exposed • Mivacurium 1 : 38,200 patients exposed • Atracurium 1: 52,800 patients exposed • Cisatracurium 1 : 148,7000 patients exposed
Explanation • Fentanyl • “To date, there have been seven reported cases of fentanyl-induced anaphylaxis” (Br. J. Anaesth. (2011) 106 (2): 283-284) • Teicoplanin • “Anaphylactic Reactions: Uncommon - More than 1 in 1000 people who have Teicoplanin” (NHS Choices website) • “Anaphylactic Shock: The frequency of these side-effects is unknown” (NHS Choices website) • Gelofusine • “Anaphylactoid reaction to Gelofusine, that contains succinylated gelatin and other plasma expanders carries an estimated incidence of 0.07–0.15%.” (Ioannis Polyzois et al. Anaphylaxis due to gelofusine in a patient undergoing intramedullary nailing of the femur: a case report. Cases Journal 2009, 2:12)
Physics & Measurement • 16) A 25-year-old woman who is 16 weeks pregnant is admitted to hospital with sudden onset of breathlessness and collapse. A transthoracic echocardiogram suggests a massive pulmonary embolus. An ECG is studied and shows sinus tachycardia with right axis deviation. The cardiac axis is likely to lie at which of these angles? • a) -60 degrees • b) +60 degrees • c) +90 degrees • d) +120 degrees • e) -90 degrees
Explanation • both I and aVF +ve = normal axis • both I and aVF -ve = axis in the Northwest Territory • lead I -ve and aVF +ve = right axis deviation • lead I +ve and aVF -ve • lead II +ve = normal axis • lead II -ve = left axis deviation
Physics & Measurement • 17) Whilst checking the anaesthetic machine in theatre you notice that a piece of monitoring equipment has the symbol of a man enclosed in a box. Which ONE of the following is not true regarding the electrical safety of this equipment? • a) It is a floating circuit • b) It cannot be used in direct connection with the heart • c) It has a maximal leakage current of 10 μA • d) It contains an isolating transformer • e) It has a maximal leakage current of 500 μA
Explanation • This is the symbol for type BF equipment. • Therefore has a maximal leakage current of 500 μA and • Cannot be used in direct connection with the heart • Equipment classified into 3 groups • Class I equipment - any accessible conductible part must be connected to earth • For this system to work correctly, fuses must be present in the live and neutral wires. • Class II equipment has double or reinforced insulation of any conductible parts • Does not have an earth wire. • Class III equipment uses batteries at a voltage unlikely to cause electrocution • But may result in microshock. Davis PD, Kenny GNC. Basic Physics and Measurement in Anaesthesia, 5th edn. Oxford: Butterworth Heinemann, 2003; pp. 181-5.
Explanation • Further classified by the maximum leakage current it allows (type B, BF and CF). • Type B or BF equipment is used in medical monitoring equipment. • Type B has a maximum leakage current of 100–500 μA under single fault conditions and should not be directly connected to the heart. • It can be class I, II or III. • Type BF is type B but also uses a floating circuit. • Type CF has a floating circuit and a maximal leakage current of 10–50 μA. It is used in equipment which may contact the heart directly. Davis PD, Kenny GNC. Basic Physics and Measurement in Anaesthesia, 5th edn. Oxford: Butterworth Heinemann, 2003; pp. 181-5.
Explanation • Circuit breakers exist that are current-operated • Consist of coils of the live wire around a transformer • An equal number of coils of the neutral wire are also wound around the transformer • A third wire connects to a relay that operates the circuit breaker • With equal currents in the live and neutral wire, the magnetic fluxes are equal and opposite and therefore there is no magnetic field. • With a small leakage current, the magnetic fluxes are different, and a magnetic field that induces a current in the third winding results in the relay breaking the circuit. Davis PD, Kenny GNC. Basic Physics and Measurement in Anaesthesia, 5th edn. Oxford: Butterworth Heinemann, 2003; pp. 181-5.
Physics & Measurement • 18) Consider a hypothetical situation in which the following gases or vapours are stored separately in cylinders in a hot operating theatre (the thermometer reads 35 degrees Celsius). Which one of the following would NOT contain gas alone, irrespective of the pressure within the cylinder? • a) Oxygen • b) Nitrogen • c) Nitrous oxide • d) Carbon dioxide • e) Air
ExplanationNitrous Oxide Storage • French blue cylinders • In a liquid phase with its vapour on top • At a gauge pressure of 4400 kPa at room temperature. • As the liquid is less compressible than a gas, the cylinder should be only partially filled. • The filling ratio is weight of the fluid in the cylinder divided by weight of water required to fill cylinder • In the UK, the filling ratio for N2O is 0.75 • But in hotter climates the filling ratio needs to be 0.67, to avoid cylinder explosion. • Hospitals store N2O in large cylinders (e.g. size J) in two groups of cylinder manifolds.
Physics & Measurement • 19) Capnography is part of the AAGBI minimal monitoring requirements for general anaesthesia. Regarding capnography, which of following is the LEAST correct? • a) Capnography is based on the principle that gases with two or more different atoms in the molecule will absorb infrared radiation • b) The particular frequency of infrared radiation is selected by first passing it through a crystal window • c) A reference cell increases accuracy of the system • d) The use of infrared radiation with a wavelength of 4.28 µm for the analysis of carbon dioxide should reduce interference from the presence of nitrous oxide • e) In the sidestream capnograph, a sample is drawn at about 150mL/min